THE

CINCHONA BARKS:

P harmacognostically Considered.

BY

FRIEDRICH A. FLUCKIGER, PH_D.,

PROFESSOR IN THE UNIVERSITY OF STRASBURG, GERMANY, AND AUTHOR OF PHARMACEUTICAL CHEMISTRY.

TRANSLATED FROM THE ORIGINAL TEXT, WITH
SOME ADDITIONAL NOTES.

BY

FREDERICK B. POWER, Px.D.,

PrRoressoR OF PHARMACY AND Marerta Mepica In THE UNIVERSITY OF WISCONSIN.

WITH EIGHT LITHOGRAPHIC PLATES AND ONE WOOD-CUT.

PHILADELPHIA:
Pz BLARISTON, SON & COG.

No. 1012 WALNUT STREET.

1884.

Entered according to Act of Congress, in the year 1884, by
P. BLAKISTON, SON & CO.,

In the Office of the Librarian of Congress, at Washington, D. C.

AUTHOR'S PREFACE.

In accordance with the progress of human development, the
_ most important vegetable remedies are, or were, to a large degree,
of Oriental or South European origin. America contributed at
first but few products; and that which has now acquired such
extraordinary significance in the National economy—tobacco—is
without importance from a medicinal point of view, although
Nicotiana was first introduced into Europe for the sake of its
medicinal virtues. A century later there appeared a remedy
from the American vegetable kingdom in the form of Cinchona
bark, the value of which has received ever increasing recognition,
even under the severest criticism of the present day. With refer-
ence to the sums of money which it sets in motion, the world’s
market may designate this bark as the most important medicinal
remedy, although its value at the present time depends much
more upon the fact of its affording the crude material for manu-
facturing industries. Since the discovery of quinine, and the
immediate subsequent preparation of the same ona manufacturing

scale, the pharmacognostical importance of Cinchona barks has ©

correspondingly changed; the greater certitude in the quantitative
estimation of the alkaloids also has the effect of forcing a know-
ledge of the external characters of the barks, as such, in the back-
ground. The revolution is slowly effected, and until within a short
period the chapter of Cinchona barks still flourished in pharma-
ceutical literature, with all of its original and extreme luxuriance.
The advances in the cultivation of the Cinchonas now render
necessary a different comprehension of the subject of “ Chhincho-
nology” (Chinology or Quinology), as, with scarcely justifiable
emphasis, this section of pharmacognosy has been named.
Unfortunately, there is still altogether too much wanting to pro-
duce satisfactory and complete symmetry. Even from a system-

atical consideration, the botanical knowledge of the respective
ili

iv PREFACE.

group of plants leaves much to be desired, to be silent regarding
an insight into the anatomical structure of their barks; with
relation also to the most important question, the distribution of
the alkaloids in these plants, we are imperfectly informed.

The sudden flooding of the market with Cinchona cuprea,
which does not belong to a Cinchona, and particularly, with regard
to its tissue, is altogether distinct from the Cinchona barks in a
more restricted sense, has brought to light that which for the
entire world is a surprising fact, that quinine and the allied bases
are not confined to the genus Cinchona. The new views which
are forced upon us by this observation presents again very par-
ticularly the question as to which plants inside the circle of the
Cinchonez contain in general cinchona alkaloids. The answer to
this in the meanwhile can be but a very incomplete one.

There are thus connected with the Cinchona barks many points
of interest, traditions which have become and remain dear to the
pharmacist and the physician, as well as views into the future,
which are likewise worthy of the consideration of a wider circle.
It was my endeavor to render prominent these points of view by
the light of the present, to arrange the not always refreshing
material of past times, and to open the path to a better under-
standing. The short distance which I have been able to traverse
_ shows, indeed, some progress, and invites to further labor.

The following lines, especially with consideration of a larger
circle of readers, have been abstracted from my ‘“ Pharmakog-
nosie,” although amplified in manifold directions. The importance
of the subject appeared to me to justify such a treatment of it.

I have hereby been assisted, in a manner most worthy of thanks,
by my friends, Dr. J. E. de Vrij, C. S. L, of the Hague, and Dr.
G. Kerner (Zimmer's Quinine Manufactory in Frankfurt).

Tue AuTuor.
Pharmaceutical Institute of the University of Strasburg.

TRANSLATOR’S PREFACE.

In presenting to the public an American edition of Professor
Fliickiger’s admirable monograph, the translator has been actuated
by the desire that so valuable a contribution to the literature of
Pharmacognosy should not be restricted in its sphere of appre-
ciation to those conversant with the German idiom, but that it
might also be rendered accessible to a still larger class of readers.

The aims and purposes which have guided the author in his
work have been clearly enunciated in the words of his preface,
and require no further elucidation. In the present edition, it has
been my endeavor to render the translation as literal as was con-
sistent with clearness of expression, and to preserve throughout
the arrangement of the original text.

The section relating to the quantitative estimation of the alka-
loids has been considerably extended. The author’s method of
assay has hereby been given somewhat more in detail, and supple-
mented by a wood-cut representing the form of apparatus origi-
nally figured and described by him. The process of Squibb, as
recently improved, has been rendered more explicit, and that of
De Vrij, as adopted by the United States Pharmacopoeia (sixth —
revision, 1880) has also been added, together with the method of
De Vrij for the determination of crystallizable quinine in the mixed
alkaloids.

Since the successful practical application of these methods of
assay, and the correctness of the results which they afford, is to so
large a degree dependent upon the careful observance of all their
details, as well as upon a knowledge of the principles involved, it
was considered that such additions would prove useful, and in
many instanees avoid reference to the original publication, not
always readily accessible.

The handsome lithographic plates of the original monograph
have been specially imported for their reproduction in this edition,

and will be found sufficiently explained in an addition to the text.
v

.

ata TRANSLATOR’S PREFACE,

Besides the above noted and a few minor additions, I have been
kindly favored by the author with numerous notes, comprising the
results of more recent observations or research, which are dis-
tributed throughout the work.

With these brief statements, the translator ventures to express
the hope that the work of his honored friend and master may also
be received in America, as in Europe, with the favor it so richly
merits, and, while aiding in the dissemination of general know-
ledge, may likewise incite to the further substantial development
of true pharmacognostical science.

MADISON, Wis., March, 1884.

SYNOPSIS OF CONTENTS.

PAGE

SECTION I.

BOTANICAL ORIGIN, fe : : . é A : . ees, *|
SECTION II.

THE Most ImporTANT SPECIES OF CINCHONA, : é é a 25

SECTION III.

REMIJIA, . ; : ‘ é : ~ ; ‘ - Ig
SECTION IV.

HABITAT OF THE CINCHONAS, ; ‘ ‘ : ; . <cRE
SECTION V.

CINCHONA CULTURE, . ‘ ‘ fies ‘ . ead
SECTION VI.

COLLECTION OF THE BARKS. MOsSING, COPPICING, UPROOTING, . . . 29

SECTION VII.
APPEARANCE AND ANATOMICAL STRUCTURE OF THE CINCHONA BARKS, . ae

SECTION VIII.

CONTENTS OF THEIR TISSUE. LOCATION OF THE ALKALOIDS, A i 2 ag
: SECTION IX.

VARIETIES OF CINCHONA BARK, é : : e 4 : ree |
SECTION X.

SO-CALLED SPuRIOUS CINCHONA BARKS, : ; ‘ ‘ - 45
SECTION XI.

CINCHONA CUPREA, . . ‘ ‘ ‘ é 5 é oe

SECTION XII.
COMMERCIAL STATISTICS, ‘ ; : . : 2 : ie

SECTION XIII.
CHEMICAL CONSTITUENTS OF THE CINCHONA BARKS. AMOUNT OF ALKALOIDS, 58

SECTION XIV.

QUANTITATIVE ESTIMATION OF THE ALKALOIDS, . . . : - 69
Vil

Vul SYNOPSIS OF CONTENTS.

PAGE

SECTION XV.
MANUFACTURE OF THE ALKALOIDS, . 5 3 ; ; : Sars:

SECTION XVI.
HIsTORY OF THE CINCHONA BARKS, TO THE YEAR 1737, - ; : cor

SECTION XVII.
THEIR HISTORY TO THE PRESENT TIME, : : R z Z . 86

SECTION XVIII.
LisT OF THE MoRE RECENT PUBLICATIONS RELATING TO THE CINCHONA BARKS, 92
INDEX, =~. . : ; ‘ : : ‘ : i - 99

EXPLANATION OF THE PLATES, ; : ‘ ; : fs - 104

CINCHONA BARKS:

, THEIR

HISTORY, BOTANICAL AND CHEMICAL CHARACTERS.

SECTION I.
BOTANICAL ORIGIN.

By the expressions Crzchona barks or Peruvian barks, Latin cor-
tices cinchone or cortices chine, German chinarinden, French écorces
de quinguina, Spanish guina, are designated such barks as contain
alkaloids of a particular group, which may directly be denoted as
the cinchona bases. These anti-febrile alkaloids have, as yet, been
met with only in the barks of the cinchonez.

In the very numerous family of the Rubiaceze the Ginchonee
belong to the series of those having dry, many-seeded, capsular
fruits, and scale-like, deciduous stipules; and within this circle they
form one of those groups which are characterized by an expanded,
branched, not contracted or capitate inflorescence. Both valves ot
the capsule contain a large number of small seeds, winged all
around by a broad membrane, which is very irregularly toothed
or lacerated at the edge (Plate III); the embryo is embedded in
richly developed endosperm.

The division of the Eucinchonee presents a valvate, not re-
flexed or imbricated corolla (Plate II), and angular funiculi in
the middle of the partition of the capsule. The genus Ginchona
is distinguished finally by a tolerably long, cylindrical, or only
very slightly contracted or expanded corolla tube. The five flatly
expanded lobes of the corolla, which are small in dimensions, are
of delicate texture, fringed at the margin (Plate II), and of a
whitish, purple, bright red or somewhat violet color. The period
of flowering of the Cinchonas continues, at least in India, through
the greater part of the year, so that fruits and flowers are usually
present at the same time. The styles of the latter sometimes pro-
ject beyond the corolla tube (Plate II, c), and are sometimes en-
closed (Plate II, b); a third form of the flower with almost sessile
stigmas and longer stamens may also be observed. While the

B 9 | |

10 CINCHONA BARKS.

fertilization of other heterostylous plants is usually effected by
insects, this appears not to be applicable to the Cinchonas, but is
accomplished rather through the agency of the wind.

The flowers are arranged in the form of abundant terminal
panicles or cymes (Plate VI). The valves of the ovate or some-
what lengthened, but usually not particularly slender capsules,
dehisce from the base in consequence of the splitting of the
partition ; but the two halves of the capsule remain connected at
the apex by the five-toothed, permanent calyx, without, however,
thus preventing the detachment of the funiculi (Plate I, III, IV).

The most closely related members of the Eucinchonee differ in
the following respects from the genus Cinchona :;—

The species of Cascaril/a, including Buena and Cosmibuena,
have larger, firm, often even leathery corolla lobes, which are not
fringed, but beset with coarse, club-shaped hairs. The capsules
dehisce first from the apex (Plate V, left),

The genus ‘emia (Plate V1), otherwise differing but slightly
from Cinchona, is distinguished by the long-stalked, interrupted
racemes, cymes or panicles, situated in the axils of the leaves.
The edge of the calyx is furthermore extended, often cup-shaped,
the capsules cylindrically compressed, ovate or nearly spherical,
and, as a rule, dehiscing first from the apex. The Remijia species
have on the contrary, in common with the Cinchonas, the slightly
attractive, red or white flowers, and even the pleasant odor of
the latter. The Remijia does not represent large trees; the
leaves of the smaller forms are occasionally arranged in whorls of
three.

In the Pimentelia the inflorescence forms compact panicles
projecting from the axils of the leaves.3 Ladenbergia and Macroc-
nemum are separated in the most striking manner from Cinchona
by their entire appearance.‘

To what extent the barks of these plants show corresponding
distinctions in regard to their anatomical structure, has been
but slightly investigated. The Condaminea, mentioned on page

1 Bentham et Hooker. Genera Plantarum I (1873-1876), 33. Baillon. Aistoire des
Plantes, V1 (1880), 479.

* The following drawings of Karsten’s in the Flore Columbie specim. select, give a good
representation of Cascarilla: C. barbacoénsis, tab. xxiii; C. Henleana, tab. Ziv: C.
heterocarpa, tab. vi; C. macrocarpa, tab. xxi.

* Weddell, in Hist. nat. des Quinguinas, tab. 27, B., gives a figure of the Pimentelia
glomerata.
_* Compare, for example, Karsten’s figure of Joosia (Ladenbergia) umbellifera, in
Flor. Columb. specim. sel., Tab. V, and Lasionema (Macrocnemum) cinchonoides, in
Weddell’s Plate 27 B.

BOTANICAL ORIGIN. ll

49, approaches the Cinchonez to some extent in this respect,
trom which, however, it must be excluded for morphological
reasons.

Cascarilla, the Remijias, Pimentelia, the Ladenbergias, and the
Macrocnemum species, in opposition to the Cinchonas, are much
more widely distributed through the tropical and a portion of the
sub-tropical countries of South America, and by no means confined
to the mountains. Among the Spanish and Portuguese population
they are all comprehended under the name of Cascarillos bobos,'
spurious or false cinchonas. The barks of many of the trees
belonging to this class are considered in their native country to
possess medicinal properties, and occasionally found their way to
Europe, particularly before the discovery of quinine. After this
period, however, it was ascertained that the so-called spurious
cinchona barks, which had already been regarded in Europe as
dubitable, contained either no alkaloid at all, or at least no anti-
febrile alkaloid, and a general inclination to the view was adopted
that only such barks contain cinchona alkaloids which possess the
structure described on page 35. This conception was corrected in
the year 1871 by an acquaintance with the Cinchona cuprea, which
occupies an intermediate position, in that it belongs anatomically
to the false, but chemically to the good cinchona barks, which
contain alkaloid. It is probable that in the course of time other
useful barks of this class will be brought to light from the above-
mentioned genera of Cascarilla, Remijia and Pimentelia. The
bark collectors, who are familiar with the appearance of the true
Cinchonas, will therefore presumably in future restrict themselves
less from a closer acquaintance with other Cinchonas, since the
Cinchona cuprea has proved itself valuable.

_ The Cinchonas or fever-bark trees, Cascarillos finos, are ever-
green, with mostly leathery, shining leaves, which are traversed by
a strong mid-rib and finely veined by delicate lateral nerves. The
thick leaf-stalk, which is often of a fine purple color, attains at the
most one-third the length of the leaf, but usually remains shorter.
In outline the leaves are ovate, obovate, or nearly circular, in some
species lanceolate, seldom somewhat cordate (as in C. cordifolia

1 Bobo signifies in Spanish, stupid or foolish. In a pamphlet printed at Lisbon in 1799,
Quinographia portugueza ou collecgao de varias memortas sobre 22 especies de Quinas,
etc. (64 pages and 17 plates, or, in another edition, 192 pages and 14 plates), the minorite
José mariano de la concepcion velloso, from the province of Rio de Janeiro, has
described 22 Cinchonas, which all belong to the “‘spurious’’ class. It will be interesting
to determine whether the bark of some of these does not indeed contain the cinchona
alkaloids. How very improbable this is, is shown by the cinchona rosa from Tucuman,
mentioned on page 50, Note 6, and also possibly the Tolima bark (page 52.)

13 CINCHONA BARKS.

Muts, and also possibly in part in C. hirsuta, C. Mutisii, and C.
pubescens) ; they are smooth, or at the most slightly revolute,
always entire, and besides often very variable on the same tree,
(as, e. g.,in C. heterophylla). With regard to size, the leaves also
vary considerably. Occasionally the young leaves are of a purple
or purplish-violet color (in Spanish morado) on the under surface ;
and the fully developed leaves of several species assume quite
regularly, directly before falling, this often very rich, dark color,
which is strongly marked, e. g. in C. purpurescens, Wedd.

The Cinchonas present themselves as handsome, even though
not precisely extraordinarily remarkable, shrubs or trees of the
tropical primeval forest, of about the appearance of the Syringa.

The genus Cinchona is one so uniform, and whose members
agree so closely, that a satisfactory definition of the latter is not
readily accomplished. The individual species are connected with
each other by intermediate forms, and form a continuous series,
the terminal members of which are moreover scarcely more sharply
separated from the above-mentioned allied genera than from
plants of their own series. In the systematic botany of the Cin-
chonas the limit of the species is therefore often dependent upon
very insignificant characters, for the justification of which doubt
prevails in many cases. According to the diversity of view in the
conception of the species, the number of species of cinchona
accepted by botanists has consequently varied. In the year 1830,
for example, the Prodromus of De Candolla accepted 18 species.
Howard’s handsome work, ‘“ Nueva Quinologia,” contains 38 species,
which are represented also for the most part by figures; but which
on the one hand must be considerably increased, and, on the other,
modified by the combination of evident sub-species. | Without
consideration of the fact that some botanists have connected plants
with the genus Cinchona, which, according to the above outlined
diagnosis of the genus (page 10), are positively distinct therefrom,
the number of good species of Cinchona which has been gradually
described has increased to about 50. A complete review of the same
is given in Weddell’s “ Notes sur les Quinquinas,” where indeed
33. species’ are still represented, while 18 others are mentioned
only as sub-species, with varieties and sub-varieties. According to
Weddell’s representation there is, however, also in those species no

1 Figures in Histoire naturelle d2s Quinguinas, 17, by Weddell ; Flor. Columb. I, tab.
VIII, by Karsten; and in Medicinal Plants by Bentley and Trimen, London, 1880, 143.

* Enumerated in Pharmacographia by Fliickiger and Hanbury, 1879, p. 355, with the
yeni an of Cinchona Chomeliana and C. barbacéensis, whtehomtint be Si ecnent from
Cinchona. | ee

BOTANICAL ORIGIN. 13

strict separation observable, but rather gives thereby to his views
the particular expression that he refers all the Cinchonas to 5 stems
(souches, stirpes). To these fundamental forms, from which all
others radiate, Weddell assigns the name of the Cinchona which,
for the respective stem, is the most striking or the best known,
namely: 1. Stirps of Cinchona officinalis, 2. Stirps Cinchone
rugos@. 3. Stirps Cinchone muicranthe. 4. Stirps Cinchone
Calisaye. 5. Stirps Cinchone ovate. The last forms accepted by
Weddell approach already very closely to Cascarillos bobos, or to
the spurious cinchonas, namely, on account of the slender cap-
sules, which dehisce from the apex.

Kuntze’ desires to have all the cinchona trees referred to four
species, and declares the numerous species represented by other
botanists, with the exception of Howard's Cinchona Pahudiana,
as hybrids of the four species, which have been described by
him in sharply discriminating diagnoses and in light outlines.

From Kuntze’s disquisition the following review is obtained :—

A. Cinchonas with coarse, not very large leaves; the capsules so
contracted longitudinally in the centre that both halves of the fruit
appear plainly evident. Each of the latter is provided with from
4 to 6 ribs, but both are held together by the widely expanded
funnel-shaped calyx of the fruit.

(1) CincHona WeEDDELLIANA is provided with leaf-pits, sevodiculi,
and is distinguished by the only slightly lengthened, nearly spherical
capsule, which is crowned by a very small fruit calyx.

(2) CincHona Panuprana, in distinction from the above, is pubes-
cent, the corolla tube is pentagonal, and the fruit calyx almost as
wide as the fruit itself.

B. Cinchonas with less coarse or thin, often very large leaves.
The capsule is somewhat dilated, almost cylindrically beaked,
scarcely contracted longitudinally, without ribs, and terminating
without contraction in the small unexpanded calyx.

(3) Cincuona Howarprana is remarkable for the not pure
green color and the significant size of the leaves, which, even in the
inflorescence, are still quite prominent, and are always devoid of
pits; and also for the remarkable width of the pale wing of the
seeds. |

(4) CrvcHona Pavontana deviates therefrom in possessing, at
least on the flowing branches, leaves of a beautiful green color,
which are provided with leaf-pits; but, on the contrary, only yellow-
_ ish-white, not bright flowers. : ee

1 Title under section 18. See Kuntze’s remarks in the Pharmaceut. Zeitung, De-
cember 2d, 1882, p. 730, and in the London Fournal of Botany, January, 1883.

14 CINCHONA BARKS.

The distinctions between A and B are very definite and based
upon good observations. As a progressive step may be promi-
nently noted the consideration of the ribs, which are represented
by the fruits of the division A; other good points of observation
are afforded by the edges of the corolla in C. Pahudiana, as also
the widely expanded form of the fruit-calyx in A. The credit is due
to Kuntze for having discovered these characteristics, which, as it
appears, on the living plant are very sharply defined. The flowers
and capsules suffer changes by drying which lead to deception, and
half-ripe fruits of the division B may, in an herbarium, for example,
present ribs which, during life at least, do not pertain to the ripe
fruit.

Between 1 and 2, as may be seen, there is no deficiency of very
positive distinctions; the species 3 and 4, to judge from the descrip-
tions and figures of Kuntze, are less widely separated.

These 4 chief species of Kuntze correspond but slightly to the 5
fundamental forms (stirpes) of Weddell. The former has observed
living Cinchonas on the Indian plantations, Weddell, the species
growing wild in Bolivia and Peru; both botanists have moreover
compared dried specimens of forms which were not seen by them
in nature. It must remain the task of a third systematic botanist
to determine anew which method of comprehension best corres-
ponds to the totality of the forms. Kuntze arranges the stems of
Weddell in the following order:—

(1) The forms of Weddell combined under C officinalis he
declares as hybrids of C. Weddelliana with C. Pavoniana and C.

Howardiana.

(2) In the rugose he recognizes C. Pahudiana and related
hybrids.

(3) Weddell’s C. micranthe Kuntze declares as C. Pavoniana
and derivatives belonging thereto.

(4) The Catisaye as C. Weddelliana and hybrids.

(5) The C. ovate of Weddell are, according to Kuntze, to be
referred to C. Howardiana.

_ It remains questionable whether anything is gained by exchang-
ing the 51 species and sub-species of Weddell for the 44 species
and hybrids of Kuntze,

If, however, it be admitted that the origin of the forms which
were met with by Kuntze in British India and Java have been
correctly recognized by him, it is still not evident why the wild-
growing Cinchonas of South America should be embraced,
collectively and individually, with the hybrids accepted by Kuntze.

The observations on the plantations have indeed proved that

THE MOST IMPORTANT CINCHONAS. 15

hybridization between the Cinchonas, which, among themselves,
are so closely related, may very easily be accomplished; but in
nature it would be scarcely possible to distinguish whether such a
mixed derivative is in question, or a form of a definite species
which has originated through other influences.

The view of Baillon,* which is moreover not based upon
thorough observation, that about 20 species of Cinchona are to be
accepted, may possibly be the most correct.

SECTION II.
THE MOST IMPORTANT CINCHONAS.

As Cinchonas of most prominent importance, the following are
at the present time to be designated :—

(1) CincHona SucciruBra Pavon, Plate I. This beautiful tree,
which attains a height of 25 meters (82 feet), bears ovate or some-
what oblong, scarcely acuminate, thin leaves, which attain nearly half
a meter (20 inches) in length, and often 35 centimeters (13.5 inches)
in width; they are somewhat reflexed on the margin, and pubescent
on the netted veins of the dull lower surface. The panicle of
flowers is but slightly attractive. The distribution of C. succirubra
in its native country is confined ; it descends from the western de-
clivity of the Chimborazo (S. Antonio de Huaranda) southward
through Riobamba, Alausi and Cuenca, to northern Peru (province
of Jaén in the department of Caxamarca) deep into the valleys. :

In Ceylon it flourishes admirably between 2000 and 5000 feet
above the level of the sea; in the south-Indian Nilagiris between
5000 and 7000 feet. C. succirubra is therefore well adapted for
improvement by means of grafting or hybridization. Such a valu-
able form, occurring in Ceylon as the product of Cinchona offici-
nalis and C. succirubra, is designated by Trimen’? as Cinchona ro-
busta.

After Weddell for a short time had presumed the C. succirubra
to be the mother-plant of the red cinchona bark, which, however,
as C. ovata (y. erythroderma) he had not recognized with sufficient
precision, Howard and Klotzsch furnished the proof of the inde-
pendent character of the plant and its importance (page 46). The

1 Histoire des Plantes. VU (1879), 342.

? Pharm. Fourn. XU (1882), 352, 801, to18. The cinchona designated there, /oc. cit.

VIII (1878), pp. 638, 805 and 825, as “‘ pubescens” or also as “‘ lanosa,”’ is not to be con-

d with C. pubescens va4/. Of the former Bidie gives a tolerably good figure in the
pamphlet mentioned under No, 3 in section 18. :

16 CINCHONA BARKS.

colorless juice which exudes upon wounding the bark of this tree
becomes, by exposure to the air, first milky, and then immediately
red, in consequence of the active absorption of oxygen by the
cincho-tannic acid.

Other figures of C. succirubra are contained in Howard’s Nueva
Quinologia, tab. 8; Bentley and Trimen’s Medicinal Plants, 142;
and Baillon doc. czt. 342 (uncolored). .

(2) Crncnona Catisaya Weddell, Plates II and III. Occurs in
part as a high tree, and in part shrub-like, as the variety g. Jose-
phiana. It is distinguished by the ovate capsule, which attains
scarcely the length of the flower. Weddell discovered this species
in the year 1847, near Apolobamba in Bolivia, northeast of lake
Titicaca ; it extends beyond the Peruvian boundary, and is dis-
tributed through the Province of Carabaya (in the department of
Puno), but not further northward. The Calisaya is also on Bolivian
territory confined to the hot, wooded, elevated valleys (Y% ungas in
the language of Aymara) of La Paz, to the seventeenth degree of
southern latitude, between 1500 and 1800 meters (4875 and 5850
feet) above the level of the sea. In the grass regions, about 300
meters (975 feet) higher, it remains shrub-like, and only a few
meters in height. .

The native designation of Calisaya is deducted by Weddell from
collt, signifying red in the Quichua language, and saya, imitated or
shaped, with reference to the bark or perhaps to the leaf. Péppig*
explains it as cad/a, signifying a remedy, and sa//a, a rocky founda-
tion. Markham interprets it as a small chief’s family, Calisaya,
which, about the year 1780, is said to have played a part in the
Province of Carabaya.

Other figures of the plant are contained in: Weddell, tab. 3;
Berg and Schmidt, Offizin. Gewdchse, XIV; Bentley and Trimen,
141; Baillon, /oc. ct. 338 (uncolored); and Howard, East Indian
Plantations, Vl to X.

As C. boliviana, Weddell has described and figured a variety of
Calisaya which is more confined to Bolivia, and which is principally
distinguished by the almost invariable purple color of the lower side
of the leaves. It appears that the characters scarcely suffice to
retain the plant as a variety, and certainly not to elevate it to a
particular species.

The English merchant, Charles Ledger, who, since the year 1845,

s resided at Puno, the chief city of the Peruvian department of
Caravaya, westward from lake Titicaca, and, among other things,
also engaged in the export of cinchona barks, was directed by the

_} Travels in Peru, Chili, and on the Amazon River, Il (1836), 218.

THE MOST IMPORTANT CINCHONAS. 17

natives, in his repeated endeavors to discover the best bark, to the
“Rojo,”* as the choicest sort. In the year 1851 Ledger met with
the respective cinchona trees on the Mamoré, a tributary of the
Madeira on the left, which has its origin in the northeast chain of
the Bolivian cordilleras, in the Province of Caupolican. It was,
however, first in the year 1865 that Ledger’s servant, Manuel Incra
Mamani, succeeded in collecting seeds of this cinchona in the same
province, 120 leguas (about 780 kilometers or 480 miles) from
Pelechuco, in about the fifteenth degree of southern latitude and 68
degrees west of Greenwich, and to deliver the same to his master.
The servant, who was imprisoned in consequence by the Corregidor
of Coroico, died shortly afterward, from the result of the mistreat-
ment which he was forced to suffer. The seeds, which Ledger offered
for sale in London without success, were bought by the Dutch
Government for Java, and then furnished plants whose large per-
centage of alkaloid was in the year 1874 definitely determined.’
Howard has described this cinchona as a variety of the Calisaya,
and figured the same very handsomely in the “Quinology of the
East India Plantations,” Part III, Plates IV, V and VI.3 The ex-
ternal peculiarities of the Cinchona Calisaya Var. Ledgeriana
(compare our plates II and III) are unimportant, and consist chiefly
in the small size of the usually pure white, very fragrant flowers,
which remind of those of Cinchona micrantha Ruiz et Pavon.s The
tube of the corolla is not contracted as in many other cinchonas;
the inflorescence is very compactly crowded, often nodding. The
capsules of Calisaya Ledgeriana are furthermore not tomentose. -
Calisaya Ledgeriana, according to Kuntze’s comprehension,
which is disputed by Howard, is a form of his Cinchona Pavoniani-
Weddelliana. Experience must first demonstrate whether by
cultivation this cinchona, which at the present time is indeed the
most valuable of all, can be retained in such a degree of excellence.

1 Rojo signifies in Spanish, red or reddish-yellow.

? Howard, East Indian Plantations, \1, 46; Pharm. Fourn. X (1880), 730.

* The diagnosis delineated by Weddell in Howard's ‘‘ Quinology of the East Indian
Plantations,” fol. 85, is, in concurrence with the latter, as follows: ‘ Cinchona Calisaya,
var. Ledgeriana How. Foliis elliptico-oblongis vel fere oblongis obtusis obtusissimisve,
haud raro ante apicem nonnihil angustis s. constrictis membranaceis, utriusque viridibus
vel subtus pallide purpurascentibus nervis simul rubico, axillis vulgo sat distinctis
scrobiculatis; panicula florifera ovata, corollis albis, antheris subexsertis (saltem in
spec. obviis), panicula fructifera subcorymbosa, densa, capsulis ellipticis (9 ad 12 milli-
metr. longis), puberulis. From this, indeed, no striking characteristic can be observed.
Bernelot Moens as well as Trimen consider Ledger’s plant as a peculiar species:
Cinchona Ledgeriana Moens; see Journal of Botany, London, 1881, p. 321, with
figure. In Darjeeling the best ‘‘Calisayas"’ are stated by King, Report of May 28,
1881, to be nothing else than C. Ledgeriana. |

* Figured in Howard's Nueva Quinologia, 5; Weddell, 14.

18 CINCHONA BARKS.

It would be extremely remarkable to see the permanency in rich-
ness of alkaloid attained here by cultivation, which otherwise does
not occur,

(3) CincHona Lancirou1a Mutis, Tuna or Tunita of _ the
Bogotians, Plate IV. More than 25 meters (80 feet) in height,
leaves sharply lanceolate, leathery, mostly 12 centimeters (nearly
5 inches), on the luxuriant sprigs as much as 36 centimeters
(about 14 inches) in length, although very variable.

This species, which has been known since 1776, is confined to
Columbia (New Granada), and grows admirably in the south, from
Bogota to Popayan, at an elevation of from 2500 to 3000 meters
(8125 to 9750 feet) above the level of the sea, but also northwards
in the mountains of the Magdalena near Chiquinquira, Velez,
Socorro, and from Pamplona to Ocanna, and, according to Howard,
also in Uchubamba, not far from Loxa.

It is very handsomely represented in Karsten’s Flor. Columb.,
tab. xi; Var. discolor. tab. xii.

(4) Cincuona Orricrna.is, the earliest named species.

In the year 1742 Linnzus established the genus Cinchona in
accordance with the notes published by Ch. M. De La Condamine,
and in 1753 named the tree discovered by the latter Cinchona of-
ficinalis, but in 1766 he gave a different diagnosis, which was based
upon the communications received by him from Mutis in the year
1764. These related, however, according to Triana (fol. 10 of
the work mentioned in section XVIII), to the C. cordifolia of the
present day. It follows therefrom that the designation Cinchona
officinalis, as established by Linnzeus, is capable of a double inter-
pretation. In his writings from 1742 to 1766 it related to the spe-
cies which Hooker in 1863 again named Cinchona officinalis, but
in 1766 Linnzus included in the diagnosis the present C. cordifolia
(not C. pubescens as has been generally believed), Furthermore
Triana, as well as his predecessors, did not find in the herbarium of
Linnzus in London specimens of a “ Cinchona officinalis,” but on
the contrary, only fragments of C. cordifolia, Cascarilla nitida and
Exostemma coriaceum, which were designated as Cinchona peru-
viana. With propriety, therefore, C. officinalis passed into oblivion ;
and it was first in the year 1863 that Sir Joseph Hooker was in-
duced to establish a new diagnosis of Cinchona officinalis, and to
complete the same by a good figure.

Cinchona officinalis Hooker, Plate V, is therefore to be re-
garded as a new species, which is indigenous to Ecuador and Peru.
It does not possess any very striking characteristics; the flowers are
small, of a beautiful carmine-red, and downy, and the oblong cap-

REMIJIA. 19

sules sometimes more than 12 millimeters (half an inch) in length.
Weddell combines under the name of C. officinalis the Cinchona
Chahuarguera, C. Condaminea, C. Bonplandiana, C. crispaand C.
Uritusinga of former systematic botanists.

A prominent distinction between C. officinalis and C. lancifolia
is not plainly observable.

Those different forms of C. officinalis probably furnished chiefly
in the seventeenth and eighteenth centuries and to the present time
the so-called Loxa Cinchona. According to Wellcome, the region
of Loxa, from the fourth to the fifth degree of southern latitude,
on the boundary of Ecuador and Peru, is now exhausted.

Other figures of C. officinalis are to be found in Hooker’s Bot.
Magazine, 5364; Howard's NV. Quinol, I, 19; Howard's East India
f7., 1X ; Bentley and Trimen’s Afedic. Plants, 140; and in Baillon’s
fiist. des Plantes, 340-341 (uncolored, but elegant).

SECTION III.
REMIJIA.

Of the most closely connected allies of the Cinchonas mentioned
on page 10 only two species of the genus Remijia have as yet
attained actual significance. The shrubs belonging to this genus
were recommended to the Brazilians first from the environs of Ouro
Preto, the chief city of Minas geraes, by a surgeon Remijo, as
Quina de Serra or mountain cinchona,’ in that they are distributed
as far as the rough, dry, mountainous regions of the Province Minas
geraes. Velloso, the Brazilian botanist, who has already been
mentioned on page 11, had described such Quina de Remiyio, as it
was also called, under the name of Macrocnemum.?_ Saint-Hilaire >
placed these plants in the series of the genus Cinchona, which at
that time was much more broadly comprehended than at present.
De Candolle* was the first to separate the genus Remijia, which,
according to Triana, at present embraces the following species: °

1C. F. Ph. Von Martius, ‘“ Die Fieber-Rinde, der Chinabaum, etc.’ in Buchner's
Repertorium fiir Pharm. X11 (1863), p. 358.

? In Vandelli, lore lusitane et brasiliensis specimen. Conimbrice, 1788.

3 Plantes usuelles des Brésiliens. 1824.

* Bibliotheque universelle de Geneve Il (1829), 185. Prodromus, IV, 357.

’ Bentham et Hooker, Genera Plantarum, II (1873), 33, accept 13 species of Remijia,
and enumerate therewith, among others, the Cinchona prismatostylis (Tab. VII) and C.
macrophylla (Tab. XXXV), which have been handsomely figured by Karsten. The
former corresponds to the character of the Remijia evidently on account of its bell-shaped
calyx, the glandular disk, and the terminal panicles. In both of the latter respects, on
the contrary, the cinchona (Remijia) macrophylla is again separated. According to Triana
(Nouvelles Etudes, 72), this is nothing else than Remijia ferruginea D. C., Prodr. 1V, 357.

20 CINCHONA BARKS.

(1) Remijia Hilarii D. C, in the Province of Minas geraes. (2)
R. paniculata D. C, in Brazil. (3) R.cujabensis Weddell (Laden-
bergia A7/otzsch), Bahia. (4) R. Bergeniana Wedd. (Ladenbergia
AT). (5) R. firmula Wedd. (Ladenbergia AZ), in Brazil. (6) R.
macrocnemia Wedd, (Ladenbergia AZ), on the Amazon. (7) R.
densiflora Benth. et Hooker, in British Guiana. (8) R. hispida
Triana, on the Orinoco, (9) R. tenuiflora Bentham, between
Barra and Barcelos on the Rio Negro, about 65° of western longi-
tude. (10) Remijia Purdieana Wedd, in the Columbian provinces
of Antioquia and Santander, in the district of the Magdalena river
and the Cauca. (11) Remijia Pedunculata 77zana, in the mountain-
ous declivities southward from Bogota and eastward to the
Orinoco, between 1000 and 2000 meters (3250 and 6500 feet)
above the sea, in the region of the Rio Mesa, Rio Negro, Guaviare,
Papamene, Zarapote, and other rivers within the domain of the
upper Orinoco and the Amazon. |

Remyia PurDIEANA was discovered near Cauvas, in the province
of Antioquia, by Purdie, the director of the garden at Trinidad
(+1837), and was described by Weddell.t It is characterized by
the long-stalked opposite panicles, which are located in the axils of
the leaves, and whose ramifications bear a rust-colored felt; the
corolla is of a firm consistence, tomentose on the exterior, and the
corolla tube narrow. Ds as

Remyta Pepuncurata, plate VI, has been met with, both by
Karsten and Triana, as a small tree 3 meters (about 10 feet) in
height on the eastern slope of the Cordillera of Bogota, on the
road in the plains of the Orinoco, near the village of Susumuco,? at
an elevation of 1000 meters (3250 feet). Karsten gives promi-
nence to the silky lustre of the hairs which envelop the young
shoots, and are also not wanting on the younger leaves. In the
fully developed leaves, the leathery lamina, which is sharply
lanceolate above and below, attains a length of 2 decimeters (8
inches), and is smooth, with the exception of isolated small bristles
on the lower surface. The inflorescence is an axillary, long-stalked
cyme, the border of the calyx bell-shaped, the Ovary covered with
a glandular ring, and the capsule dehisces through the partition
from the apex to the base, more rarely from the base to the apex.

} Annales des Sciences naturelles, Bot. X1 (1849), 272. The diagnosis is as follows:
“foliis oblongis, basi attenuatis, abrupta acuminatis, planis, demum glabratis; panicu-
la subtorymbosa, bracteis foliaceis integris, bi-tridentatis ; floribus subcapitatis. banice:
le axillares, opposite, longe pedunculate, subcorymbosae pedunculis ramulisque fer-
rugineo-tomentosis. Corolla membranacea, extrorsum puberula, tubo angusto 1 centim.
longo. . . .” (The capsule was not at Weddell’s command.)

? Between this village and Villavicencio (Triana),

HABITAT OF THE CINCHONAS. 91

Of the most closely related species, Cascarilla heterocarpa,’ C.
magnifolia,? and C. Riveroana,? the Remijia pedunculata is distin-
guished by the axillary inflorescence, by smaller capsules,* and the
leather-like leaves. In plate XXVI of the Flore Columbie
Specim. select., mentioned in section XVIII, Karsten completes the
above description’ of R. pedunculata (still designated by him as
Cinchona) by a handsome figure of the same.

According to Triana’ the two last named species are very
positively distinguished from each other. The calyx teeth of
Remijia Purdieana are much longer than the calyx tube, and
nearly linear, the stipules sharply lanceolate, and the capsules
more slender than in Remijia pedunculata. The short calyx teeth
of the latter are roundish triangular, and the broad stipules obtusely
ovate.

Both species of Remijia afford the barks described below as
Cinchona cuprea, and must therefore, at least the Remijia pedun-
culata, occur abundantly in the wide domain from the Magdalena
river to the eastern declivities of the Cordilleras, southeastward
from Bogota.

SECTION IV.
HABITAT OF THE CINCHONAS,

The Cinchonas are confined to the Cordilleras, whereas the
other Cinchonee inhabit a far more extended area under the most
diverse climatic relations. In other districts of South America,
which apparently fulfill the same physical conditions as the cinchona
belt of the Cordilleras, no true cinchona trees have indeed as yet
been met with.

1 Karsten, tab. VI.
* Howard, WV. Quino/., tab. X ; presumably not different from C. heterocarpa.

* Figured under the incorrect name of C. Ruizii in Weddell’s Hist. nat. des
Quinguinas, tab. XXIII.

* The pear-shaped capsules of Remijia pedunculata, dehiscing from the apex, for
which I am indebted to Dr. Triana, are 8 millimeters (about three-tenths of an inch) in
length, with a maximum diameter of 5 millimeters (one-fifth of,an inch).

* Flor. Columb. Specim. sel. 54, where the diagnosis is embraced in the following
words: ‘‘Cinchona foliis cortaceis, danceolatis vel ellipticis, calvis, subtus in costa
nervisque paullum pilosulis; stipulis magnis obovatis quam petioli longioribus; in das?
connatis, extus pilosis, intus ad basin area triguetra imo serie villorum tectis ; cymis
axillaribus foliis longioribus, corymbiformibus, pedunculo communi longissimo, ramis
minute bracteolatis ; corollis membranaceis, extus sericeis, limbi laciniis supra barbatis ;
staminibus tubo coroll# medio insertis, inclusis; filamentis glabris, brevibus; azther-
arum rimis ciliatis; capsulis compressis, sublignosis, lanceolatis, 15 ad 18 millimetr.
longis, ab apice ad basin, rarius a basi ad apicem, septicide dehiscentibus, pilis minutis
adpressis ; seminum ale ciliato fimbriate, imperforatz.”’

* Pharm. Journ. XII (1882), 862; also Journ. de Pharm.V, 567.

29 CINCHONA BARKS.

However much the latter are confined ina vertical direction, yet
they accompany the chief South American mountain range through
the greater portion of the northern half, for a distance of about
30 degrees of latitude.

The most northerly locality of the Cinchonas, which is approxi-
mately below the tenth degree of latitude, is designated by the
occurrence of C. cordifolia in the district S.S.W. from Caracas,
with which species C. tucujensis Karsten is also here associated.

Weddell, who penetrated the cinchona zone from the southeast,
met at about the nineteenth degree of southern latitude, far in the
interior of Bolivia, with the most southerly species, which he ac-
cordingly designated as C. australis. The country west of Chu-
quisaca (Sucre), the chief city of Bolivia, would form, according to
Weddell, the southern boundary of the Cinchonas. It appears,
however, that this must be still further extended, and about to the
twenty-second degree of southern latitude, for Scherzer’ relates of
a clergyman in Tarija (on the Argentine boundary, in the south of
Bolivia), who is said to have offered for sale 3000 hundred weight
of excellent bark, sucupira of the Indians, which was procured
from the forests between Tarija and Cochabamba, thus from the
water-shed between the Marannon and the La Plata.

Between these extreme points in the south, and the mountains
of Caracas, not far from the Caribbean sea in the north, the belt of
the Cinchonas, following the crests of the mighty mountain chain,
describes a crescent, opened toward the east,of about 500 geograph-
ical miles in length. :

The conditions under which the Cinchonas live may be deducted
already in part from the above intimations with regard to the occur-
rence of the most important species, and, in indited form, haye been
elaborately elucidated by Martius,’ and still more accurately, on the
spot itself, by those English travelers who have distinguished them-
selves by the removal of the cinchona trees to India and the Colo-
nies. Only the variable, sunny climate of the tropical mountain
regions, which is interrupted by frequent showers, storms, thick fog
and mist, with very changeable but not widely digressing ranges
of temperature, is adapted to the Cinchonas. A transient depres-
sion of temperature to the freezing point, and not unfrequent
showers of hail, may indeed be borne by strong plants; yet the
mean temperature most favorable to them should be estimated at
not less than from 12 to 20° C. (54 to 68° F.). According to the

1 Voyage of the Austrian frigate Novara, 11 (1859), 366.
_? Buchner’s Repertorium fiir Pharmacie, X11 (1863), 362, 373.
* Complete reports in the Blue Books cited under section 18.

G HABITAT OF THE CINCHONAS. 93

opinion of the bark collectors, however, a proportionately cooler
location, extending to the uppermost boundary of forest vegetation,
favors the formation of alkaloid. A considerable exposure to direct
sunlight appéars to be injurious to young plants, but decidedly
favorable to strongly developed trees, and particularly also to
increase the brightness of color of the bark, which in commerce is
so highly prized.

As the precise habitat of the Cascarilla fina, the best cinchona
bark, Karsten* unhesitatingly designates the foggy region of the
Andes chain, which is intercepted by deep valleys, with a mean
temperature of 12 to 13° C. (53.6 to 55.4 F.), where, through nine
months of the year, rain prevails, and an actual alternation of sea-
sons occurs to so slight an extent that the Cinchonas continually
bear flowers and fruits. The lower region, in which already a dry
season may be distinguished, contains chiefly large-leaved cinchona
trees of less medicinal power, together with the worthless “ Casca-
rillos bobos.”

From the dimensions already stated it is manifest that the Cin-
chonas belong to the medium and higher forms of the tropical
primeval forest, but are, however, overtopped by the far more
mighty representatives of the Artocarpez, Lecythidee, Sapindacez,
Terebinthacez, the palms, and many others.

The richness of the tropical flora excludes a uniform constituency
of the forest, and accordingly the Cinchonas also live mostly dis-
persed, at the most, forming here and there smaller groups, which
in the distance are discriminated more by a particular color than
by a striking arrangement of the complete picture of the primitive
forest. Such spots (manchas) in the variegated carpet of the
crowns of foliage are espied by the disciplined eye of the bark col-
lector (cascarillero) at the remotest distances,’ even at a time when
they are not decorated by the rich flower clusters.

Extended groups of C. corymbosa, which almost deserve the
name of cinchona forests, were met with by Karsten} on the
boundary of New Granada and Ecuador, on the western declivity
of the volcanoes Cumbal and Chiles.

The Cinchonas may always be designated as a very remarkable
member in the vegetative dress of their surroundings, so that the
portion of the South American mountain regions inhabited by

1 Medicinische Chinarinden Neu-Granadas, p. 12-13.

? Weddell, His¢. nat. fol. 9. 10; also Wellcome: ‘‘A visit to the native Cinchona forests
of South America,” Proceedings of the American Pharm. Association (1879), 814-830;

reprinted in the Pharm. Journ. X (1879), 980, and abstracted in Just’s Botan. Jahresbe-
richte, 1880. :

* Medic. Chinarinden, p. 20.

24 CINCHONA BARKS.

them, at an elevation of 700 to 2900 meters (2275 to 9425 feet),
was prominently noted by Humboldt as the region of the tropical
oaks and Cinchonas. :

Weddell excluded the cinchonez which generally inhabit lower
altitudes and do not contain alkaloid, and drew for the zone
of the true cinchona trees the boundaries of elevation at 1600
and 2400 meters (5200 and 7800 feet). The lowest altitude at
which the true Cinchonas occur in their native country is at an
elevation of 1200 meters (3900 feet), and the uppermost line is to
be accepted as 3270 meters (10,630 feet), or, in accordance with
KarsTEN, as 3500 meters (11,375 feet). With the distance from
the equator the average altitude of the Cinchona zone becomes
considerably decreased, although the Cascarillos finos do not read-
ily descend lower than 2000 meters (6500 feet). C. succirubra
occurs exceptionally as low as 800 meters (2600 feet); but by its
very large, not precisely leathery, leaves, as also by the slender
fruits, likewise does not agree with most of the other species of
valuable Cinchona.

SECTION V.

THE CULTURE OF THE CINCHONAS.

The earnest desire to subject the Cinchonas to the careful at-
tention of forest husbandry, in more conveniently located districts,
must have excited activity as soon as some scientific information
had been obtained regarding these trees. Even Condamine, to
whom we are indebted for the first description of a Cinchona, had
sought to transport young cinchona plants to Europe, but lost
them by the waves at the mouth of the Amazon river.* Mutis
was probably the first who, in Mariquita (see section 17), oc-
cupied himself with the cultivation of the Cinchonas.’ In earlier
times the Jesuits in Bolivia had also already imposed upon the
Cascarilleros the obligation to plant 5 seedlings in the form of a
cross +:+ for each cinchona tree that was felled.3

The idea of transferring the cinchona trees to the old world was
ever newly revived,* and experiments relating thereto were also
not completely wanting. Suchan one, for example, emanated, in
. H. von Bergen, Monogr. der China, 117, after Condamine’s Relation d’ un voyage,
erc. :

2 A von Humboldt. ‘ Ueber die Chinawdlder in Siidamerica.”’ Der Gesellschaft

Naturforschender Freunde zu Berlin Magazin fiir die neusten Entdeckungen in der
Naturkunde, \ (1807), 57-68.

8 Howard. Last Indian Plantations, Ill, 49.

* Compare the English B/ue Book of 1863, fol. 1; Delondre et Soubeiran (Title under
section 18); Oudemans Handleiding tot de Pharmocognosie, Amsterdam 1880, p. 146.

ae

THE CULTURE OF THE CINCHONAS. 25

1849, from the Jesuits in Cuzco, in central Peru, who sent Cin-
chonas to their settlements in Algeria.t These endeavors in
Algeria remained unsuccessful, but attracted the attention of the
Dutch, so that finally, in 1851, Miquel’s repeated impulsions
received the approbation of the Colonial Minister Pahud, who now
realized the excellent idea, and later, in 1855, being advanced to
the position of Governor-General of the Dutch East Indies, actively
assisted in its accomplishment. Pahud accordingly effected the
despatch of the German botanist Hasskarl to South America, which
took place in December, 1852, from Southampton; in 1853 he trav-
eled from Lima, through the district of Cuzco, as far as Sandia, on
the Bolivian boundary, and finally, after a repeated visit to Bolivia,
the collections, contained in 21 Wardian cases, were, on the 21st of
August, 1854, successfully brought on board of a frigate which the
government had sent to Islay for this express purpose. Hasskarl
brought the young plants in December, 1854, to Batavia, and cared
for their settlement in Java ;* the seeds collected by him were at
the same time transferred to the University gardens in Holland.
But the Dutch had also been otherwise active. In 1848 Weddell
brought seeds of Cinchona Calisaya to Paris, which there de-
veloped well, in the commercial garden of Thibaut and Keteleer,
In 1852 the Dutch Government sent young Calisaya plants of this
firm to Java, and likewise in 1854 the seeds of Cinchona lancifolia,
obtained through Karsten from Columbia. The gardens in Hol-
land furthermore soon furnished from Hasskarl’s seeds strong
plants for Java; the first results there from all these endeavors
corresponded, however, but little to the expectations.

On the part of the English, a report from Royle in June, 1852,
addressed to the East India Company, gave an impulse for the

energetic pursuance of the planting of Cinchona trees. The
learned botanist recommended for the settlements in India the Blue
Hills (Nilagiris, Neilgherries) of the Malabar coast and the south-
ern promontories of the Himalaya.

After the but slightly satisfactory attempts of the Government,
through the intervention of the English agents, to attain the pur-
pose in view, Markham finally came forward, in April, 1859, with an
offer to accept the matter, for which he was rendered capable by a
thorough acquaintance with the land and people of the domains on

1 Journ. de Pharm. XX (1851), 286; compare also Weddell, “Sur Ia culture des —
Quinquinas, communication faite au Congrés international de Botanique tenu a Paris en
Aoit 1867.” ¥ oe

* A most complete description is given by Oudemans, /oc. cit. 146, and following ; also
by Gorkom (Title under section XVIII). fe

$ Blue Book of 1863.

c

~

296 CINCHONA BARKS.

the borders of Bolivia and Peru, as also by a knowledge of the
Spanish and Quichua languages, and also already with the most
important Cinchona trees. Being well aware, from the nature of
things, of the underlying difficulties, Markham earnestly insisted
that nothing should be neglected which could ensure success.
It was of great value that he effected the appointment of the
distinguished botanist, Spruce, who was at that time traveling
in Ecuador, for the obtainment of the C. succirubra, as also the
services of Prichett, likewise resident in South America, for the
region of Huanuco in central Peru, 10° S. latitude. A very com-
petent gardener was afterward (1861) secured, in Cross, an original
companion of Spruce, who collected still more of the seeds and
young plants of the best species, and placed them with his own
hands in India. Markham reserved for himself the border-lands
of Peru and Bolivia, in order to obtain C, Calisaya, and for this
purpose started from Islay in March 1860. Having arrived in the
middle of April, by way of Arequipa and Puno, at Crucero, the
chief city of Caravaya, he met, not far from Sandia, with the first
thickets of C. Josephiana, then also C. boliviana, C. Calisaya and
others. Markham thus secured for himself 456 young plants,
which were successfully shipped at Islay, toward the end of June.
The ripening of the seeds of the Calisaya, which takes place in
the month of August, could not be waited for, in consequence of
the hostile disposition of the people of the country with regard to
the enterprise ; and in general very great difficulties were required
to be overcome, of which the leader of the entire expedition has
projected a picture which is as instructive as it is interesting.’

Further settlements of the precious plants were begun in 1861,
at Hakgalla, in the central mountain districts of Ceylon, at an ele-
vation of 5000 feet; in 1862 at Dardschiling (Darjeeling), in the
southern part of Sikkim, in the southeastern Himalaya; in 1865, in
New Zealand and upon the Australian continent, for example, in
1866, in part through private citizens, at Brisbane (Queensland, on
the eastern coast of Australia). As the primary central point of
the entire undertaking, however, Utacamand (Ootacamund), be-
tween I! and 12° N. lat., is prominent, together with its branches,
extending as far as the southern point of the Indian peninsula, in
part at elevations of about 8000 feet above the sea. Before the
arrival of Markham with the first young Cinchonas from Bolivia,
the most careful examinations, froma meteorological and geological
_ standpoint, had led to the selection of this locality. In addition
_ thereto, occurred the fortunate circumstance that. the plantations
> Markham’s Reports in the Blue Books, and his monograph “ Peruvian Bark.”

THE CULTURE OF THE CINCHONAS. 27

here were placed in charge of the experienced gardener, William
Graham Mac Ivor (died June 8, 1876), who applied to his task the
greatest zeal, and also discovered methods for the rapid multipli-
cation of the Cinchonas.

The plantations of Java, which in the beginning were not in a
perfectly satisfactory condition, flourished to such an extent after
the year 1856, under Junghuhn’s management, that in December,
1862, there were already, at 10 different places: 1,360,000 seedlings
and young trees, of which, however, the most valuable species
were in the minority. The experiences in Java led to active and in
part very bitter discussions, which were terminated on the one hand
by the death of Junghuhn (April 20, 1864), andon the other by the
highly meritorious analytical investigations of J. E. De Vrij. In the

ear 1857 the latter chemist‘ was despatched by the Government
of Holland to Java, in order to follow the entire cinchona question
in its chemical considerations. In 1864, K. W. Van Gorkom was
appointed superintendent of the cinchona plantations in Java,
which at the present time are successfully directed, also in their
chemical considerations, by J. C. Bernelot Moens.

In September, 1866, John Broughton was appointed by the
English Government for the chemical superintendence and direc-
tion of the plantations at Ootacamund, and rendered very im-
portant service until December, 1874, when, in consequence of
disagreement with the authorities, he resigned his position. The
vacancy thus incurred has recently been filled by the appointment
of M. A. Lawson, professor of botany at Oxford, as superintendent
of the government cinchona plantations.’

The success of the great exertions, which in the main are de-
lineated in the above outlines, finds a living expression in the fol-
lowing facts. On March 16, 1859 De Vrij laid before the resident
Governor-General Pahud of Java the first crystals of sulphate of
quinine, which he had prepared in his laboratory at Bandong, from
bark grown by himself upon the island. Howard, of London, like-
wise reported to Markham, in May, 1863, that he had obtained from
500 grains (about 30 grams) of the bark of Cinchona succirubra
grown in India the sulphates of quinine, cinchonidine and cin-
chonine.t Furthermore, in August, 1867, the importation of Indian
barks into London commenced ; and of the first supplies, the bark

1 Dr. DE VrY was appointed May 6, 1857, and resigned, on account of his health, in
September 1863.

2 London Journal of Botany. Jan. 1883, p. 32.
8 Written and verbal communications of my friend Dr. De Vrij.
* Blue Book, 1866, p. 14.

98 CINCHONA BARKS.

of Cinchona succirubra from the Denison plantation near Ootaca-
mund, | have preserved a specimen.’

In October, 1870, the first 750 kilograms (about 1650 pounds) of
cinchona bark from Java arrived at the Amsterdam market; a
second portion followed in March, 1872, and since that time increas-
ing consignments of Javanese barks arrive regularly, from year to
year, in Holland. In the second quarter of the year 1882 the
Government plantations in Java consisted principally of Calisaya
Ledgeriana, comprising in the aggregate nearly 114 million
plants.’

Among the very numerous points of the old and new world in
which plantations of Cinchonas are now in progress of rich develop-
ment, the following, with relation to the world’s market, come
now particularly into consideration: the plantations of the English
Government near Hakgalle in Ceylon, in the Nilagiri Hills near
Ootacamund, as also in the promontories of the Himalaya in British
Sikkim near Darjeeling,’ Mungpoo, Sitting and Rungbee. In the
second place, the numerous cinchona forests of the Dutch Adminis-
tration at Java. Independent of these State enterprises, an incentive
has thus been given to the establishment of a large number of
private plantations, for the condition and productions of which,
however, no similar reports are at hand as are regularly deposited
by the English and Dutch Administrations in their most instructive
publications, and communicated in a liberal manner.

Jamaica, in 1880, also began to bring cinchona barks into the
market.

Finally, in the native country of the Cinchonas itself, plantations
are in progress ; for example, on the Mapiri, in the Bolivian province
of Larecaya, and also in the Yungas (see p. 16).

There is no deficiency of guides for the establishment and
management of the cinchona plantations; some of the publications
relating thereto from India are mentioned in Section XVIII, under
the names of Bidie, Gorkom, King, Mac Ivor, and Owen, and in
addition to these, such information has also been recently received
from Jamaica.* |

In India the Cinchonas have at an early date become injured by
beetles (Melolontha) and caterpillars,’ and recently a critical enemy

Pharmacographia, 2 edition, p. 351, Note 2.

_ _? The recent volcanic eruptions in Java (August, 1883) are reported to have pro-
duced great destruction among the cinchona plantations. (F. B. P).

* At an elevation of 2113 meters (6930 feet) above the sea, and since 1882 in railroad
communication with Calcutta,

* Pharm. Fourn. XII (1882), 748.
Ԥ Blue Book, 1866, p. 170.

COLLECTION OF THE BARKS. 29

of the cinchona plantations has revealed itself there, in the form of
the small hemiptera, //elopelits Antonii Sigm., or the so-called “tea-
bug” of the English planters. The female of this insect, which also
produces damage in the tea plantations, deposits its eggs, from 8
to 14 in number, in the tops of the cinchona branches and in the
leaf-stalks, and causes thereby the disease of the trees known by
the name of &inarest, in that the young wingless insects nourish
themselves at the expense of the young leaves.'

The barks containing alkaloid which, under the name of Cinchona
cuprea, have recently attained such prominent significance, belong
to the genus Remzizza,? which grows under climatic conditions quite
different trom most Cinchonas. If the forest husbandry will now
also assume control of the valuable Remijias, the cultivation of the
febrifuge trees may be extended in wide domains of territory from
which they have hitherto been excluded. In distinction to the
Cinchonas, the Remijias are not confined to the mountain regions,
but are capable of enduring dryness and higher temperatures,
which, for example, prevail in the climate of the Llanos, in the
domain of the Orinoco and the Amazon. It is easily possible that
among these or other related trees still more may be discovered
with barks containing quinine, which would repay cultivation.

SECTION VI.

COLLECTION OF THE BARKS.

The hardships of bark collecting in the slightly accessible primeval
forests of South America are undertaken only by the half-civilized
Indians and people of mixed race, in the pay of larger or smaller
speculators or companies located in the towns. All who are
engaged in the business, especially the collectors themselves, are
called Cascarilleros practicos, or also Cascadores, from the Spanish
word Cascara, bark. A major-domo, placed at the head of the
collectors, directs and superintends the proceedings of the several
bands in the forest itself, where, in huts of light construction, the
provisions and afterwards the produce are deposited. Weddell, as
also Karsten and Wellcome,’ have given in a striking manner, as
eye-witnesses, a picture of these operations.

The cascarillero, by means of a sabre-like knife, Machete (machiar

? Bernelot Moens, also K. W. Van Gorkom, in the writings mentioned in Just’s Botan.
Fahresbericht, 1879, pp. 314 and 319. .

? Compare pages 16 and 54.

* In the writings previously mentioned, p. 23, and in Section XVIII. I am recently
also indebted to Dr. Chas. Robbins, of New York, for such reports. :

380 CINCHONA BARKS.

= to become bare), first deprives the exterior of the stem of the
often luxuriant climbing and parasitic plants, and begins immediately
also in most cases to scrape off the sapless layer of bark, after the
same has been rendered soft by beating. In order to detach the
valuable inner bark, longitudinal and transverse incisions are made
with chisels, as far as can be reached on the stem. The tree is then
felled, and, together with the branches, divided, and the stripping
finally completed. In most cases, especially after previous beat-
ing with a mallet, the bark, notwithstanding its slight coherence
in many species, separates easily from the wood.

Any considerable quantities of the barks must, at least in many
districts, be quickly dried by a fire, which is usually built upon the
floor of lightly constructed huts. By means of the stems of palm
leaves, bamboo stalks, or other suitable parts of plants, large hur-
dles are constructed over the fire, upon which the barks are from
time to time rearranged. The walls of the huts are also constructed
of the same lattice-work, and likewise receive large pieces of the
bark. In New Granada the drying of the bark is effected almost
exclusively over a fire.

The process of drying, however, is not permitted to be conducted
too hastily, even when it is required to immediately protect the
barks from mould, as but slightly excessive heat destroys the alka-

loids. With this imperfect arrangement, which is the only one
' possible under the described conditions, the article apparently only
then assumes a salable appearance when the drying has been
continued for three or four weeks.

In Southern Peru and Bolivia, however, according to Weddell’s
representation, even the thickest Calisaya barks are dried only by
exposure to the sun, without requiring the aid of a fire.

That the bark of the branches is not deprived of the corky layer,
requires no explanation. With regard to the barks of the stem,
it depends in part upon the commercial use, whether they are fur-
nished unaltered or peeled; but in part the anatomical conditions
also probably have some influence. Where an abundant and
deeply penetrating formation of bork occurs, as in C. Calisaya,
the removal of the worthless cork is very easily and completely
effected ; in other species, on the contrary, such a natural separation
of the corky layer does not take place to the same degree, and the
altogether too circumstantial process of peeling is omitted.

From the report of the personal observations of Wellcome in
Ecuador, a Cascarillero, after having espied from some higher
point a tract of forest that indicates sufficient value, procures, by
the payment of a small fee, a title from the Government. The

COLLECTION OF THE BARKS. 31

forest district which is thereby allotted to him, for whatever of
profit it may yield, he names after some holy person—for example,
Bosque (forest) of San Miguel. In consideration of titles of this
kind for several such Bosques the master Cascarillero may receive
from acommercial house advancements of money, in order to en-
gage the services of occasionally from 300 to 400 laborers, Peons,
which, in October or November, he guides into the forest. The
men begin their activities by the erection of bamboo huts, and are
then divided into sections, at the head of whicha Fefe, Captain, is
usually placed. For the search of the trees, felling them, cleaning
and peeling the trunks, digging up the roots, and drying the bark,
a proper division of work is assigned to the several sections. The
peons transport the bundles of bark, weighing about 150 pounds,
to large depositories, whereby many succumb to their immoderate
exertions and often insufficient nourishment; others are carried
away by malarial fever, so that not unfrequently one-fourth
of the men suffer destruction. The final sorting and_pack-
ing in serons' (heavy sacking is at the present time meet-
ing with increased use), as also the admixture of inferior barks,
takes place mostly in the magazines, “ bodegas,” of the seaports.
It is said that only a few bark dealers are ultimately successful in
accumulating wealth.

The thinner bark of the less developed portions of the stem
rolls up, upon drying, into quills (caxutos, canutillos), while the
pieces stripped from the stronger stems are very often made to
receive their flat form ( plancha, tabla) by placing them for a short
time one upon another and loading with weights,’ then exposing to
the sun, and repeating this treatment several times.

After drying, the barks are either sorted, chiefly according to
their size, or all are packed together, without distinction, in sacks
of manilla-hemp (the bast of the agave-like Fourcroya), or in linen
or cotton material, in the form of bales, containing about 100
pounds. In some places, as at Popayan, the bark is even stamped,
in order to reduce it to the smallest possible bulk. The large
dealers of the seaport towns then enclose the bark in raw bul-
lock hide (zurron), which, having been previously moistened, com-
presses the contents most firmly upon drying. In many places,
particularly in the neighborhood of Loxa, wooden chests are also
employed for the transportation of the bark.

In the domain of the Cordilleras the transportation of the barks

1 Zurron signifies in Spanish a pouch or bag made from cowhide, or also the hide itself.

2 The handsome frontispiece in Weddell’s Yist. nat. des Quinguinas represents this
occupation in the forest of San Juan del Ora, province of Carabaya, _

32 CINCHONA BARKS.

over the pathless mountains is attended with great difficulties,
which frequently forbid the employment of direct routes ; in most
cases also serving to prevent the exportation of bad barks, which
would not repay coilection. Karsten, as also Wellcome, thus ex-
plains the reasons which occasionally compel the bark dealers of
the upper Cauca valley, in the districts of Popayan, Pitayo,
Almaguer, and Pasto, not to take the route to the nearest seaport
of Buenaventura, and not directly to descend the Cauca, with its
numerous cataracts, but rather the elevated passes of Quindiu
(nearly 4000 meters = 1300 feet above the level of the sea) and
Huanacas in the valley of the Magdalena river. But also upon
the latter a relading must take place near Honda, before the barks
can continue their voyage to Baranquilla, at the mouth of the river,
and reach the near seaports of Sabanilla and Carthagena. The
export from these Columbian places has recently become very
significant.

It is only exceptionally that cinchona barks, for instance those
from Huanuco on the Ucayali and other tributaries of the Ama-
zon, have been conveyed to the Atlantic coast, to Para.’ ;

In the year 1819 Calisaya bark was conveyed by land along the
Paraguay and its tributaries, or down the stream, to Buenos
Ayres.”

For Ecuador the ports of Esmeraldas and Guayaquil are of im-
portance, while the export from the more central ports of Peru is
less considerable. The southern ports, Islay, Iquique, and especially
Arica, receive the barks from Carabaya and the high valleys ( Yus-
gas) of Bolivia.

The regular settlements of Cinchonas, which are now in a state
of progressive development in many lands, especially in India, ad-
mit of much more rational management, and a planless felling and
stripping of the trees is there out of the question.

With regard to the collection of the barks, two methods are
competitive in their claims for superiority—the treatment with moss,
_or “mossing,” and the felling system, or “coppicing.” The former

consists in separating from the stem vertical strips of bark, only
about 4 centimeters (11% inches) in width, and afterwards envelop-
ing the stem in moss. The bark renews itself very speedily on
the denuded places, becomes stronger than before, and even richer
in alkaloid. In India, clay is now beginning to be employed instead

* Compare Howard's description of such a direct importation of cinchona bark into
England, Seeman’s Fournal of Botany, V1 (1868), p. 323; also my essay in Vorwerk's
Neues Fahrbuch fiir Pharmacie, XXX1 (1869), p. 15.

7 H. von Bergen, Monogr. der China, p. 287.

COLLECTION OF THE BARKS. 83

of moss, and in Java the Alang-Alang grass (Imperata Konigii) is
applied to this purpose. When the covering of the peeled stems
is effected by either of these methods, there is to be distinguished :
1, the unaltered bark, which is first removed ; 2, the strips of bark
which are allowed to remain, and afterward subjected to treatment
with moss—the so-called “mossed bark;” and 3, the “renewed
bark.” If it is indeed possible through a long series of years to
separate the bark of the Cinchona trees in strips, as above de-
scribed, and even to effect an increase of alkaloid, at least in the
renewed bark, this method would possess much that is alluring. It
remains, however, questionable whether the trees are thereby
capable of regaining strength. The mossing process was discov-
ered and very strongly recommended by Mac Ivor, the meritorious
director of the Cinchona plantations at Ootacamund.’

Greater security for the maintenance of the trees is perhaps
presented in the procedure suggested by Bernelot Moens, in Java,
in the year 1880, according to which the bark is not removed to
the extent of its full development, but only “scraped.” Much more
care also is taken to leave a sufficient coating of bark on the entire
circumference of the stem.

The idea readily suggested itself, in the case of the Cinchonas, to
employ that form of utilization which admits of application with
woody plants, as far as this relates to the most abundant obtain-
ment of a constituent or a definite amount of such, entirely without
consideration of the further development of the plant itself. This
is the method of stripping, which is in use in Europe, especially in
the case of the oaks,’ also in Sicily, with regard to the manna-ash,3
and in Ceylon with cinnamon.t| The Cinchonas are subjected to a
similar treatment the more willingly, since the root barks, which fall
off by the occasional clearing of the cinchona plantations, have proved
themselves very valuable. According to this method of procedure,
or coppicing, which is now customary, especially in Java and Cey-
lon, the stem, at the age of about 8 years, is felled 15 centimeters
(6 inches) above the ground, and stripped, whereupon side-shoots
develop, which, after another 8 years, furnish bark rich in alkaloid.
By this stripping process the roots may also be obtained in pro-
portionate amount; an operation especially related to this is dis-
tinguished as “uprooting.” The root barks, which were formerly

1 Blue Book, more completely described in the illustrated publications of Mac Ivor,
mentioned in Section XVIII. With relation to Java, compare the annual reports of
Bernelot Moens, also Oudemans, Pharmakognosie, p. 163. - eS: sie

2 Compare Fliickiger, Pharmakognosie, p. 473. sc
8 Ibid, p. 21. * Ibid, p. 565.

34 CINCHONA BARKS.

neglected, have uniformly revealed themselves to be remarkably
rich in alkaloid.

It can only be conclusively decided by longer experience whether
coppicing or mossing is permanently entitled to preference.
Further information on this subject is contained, among others, in
the English Blue Book on the Indian Cinchona plantations of 1877.

Broughton has shown that the amount of alkaloids appears to
diminish somewhat upon drying. He finds it most advisable to
dry the bark without delay, but at the lowest possible tempera-
ture.’ In Java the employment of artificial heat has been consid-
ered. The moisture contained in fresh Indian barks may easily
amount to over 70 per cent.; the bark which is used for exporta-
tion, compared with the powdered bark dried at 120°C. (248°F.),
retains on an average, according to the determinations of Bernelot
Moens, 13.5 per cent. of water.

SECTION VII.
APPEARANCE AND ANATOMICAL STRUCTURE OF THE CINCHONA BARKS.

With regard to the development of the bark, the Cinchonas show
some distinctions. Many are distinguished from an early age by
an abundant exfoliation of the outer surface. This is especially the
case in C. Calisaya, with its bork scales attaining as much as 1 centi-
meter (3¢-inch) in thickness, and also in C. micrantha, while in
others a voluntary ejection of the cork or bork takes place toa
less extent, and in these it is not so readily removed, even by
beating.

Other species succumb to the peculiar bork formation only at an
advanced age, and only on the lower portions of the stem and on
the root.

In the barks of younger stems or branches, a grayish, sometimes
light, sometimes blackish color predominates; the outer surface of
thicker stems, on the contrary, displays a more characteristic brown,
yellow or reddish color, which is particularly prominent after the
removal of the corky layers. Although differences in the tint of
the bark may be produced by the locality, and especially by the
manner of drying, yet Karsten nevertheless gives prominence to
the permanency of their inner fundamental color on the stem, and
on the branches and twigs of the same species.

: In the fresh condition, however, these colors are very pale, and
it is only after peeling, and especially upon drying, that they fully
* Blue Book, 1870, p. 239.

ANATOMICAL STRUCTURE. 85

acquire their peculiar tint. The light grayish-yellow or yellowish-red
bark of C. micrantha begins to assume a blood-red color imme-
diately after its separation; the white bark of C. australis changes
to a rust color, as soon as the external layer which has been beaten
softis removed. In C. Calisaya the fresh bark is externally of a light
greenish-yellow color; in C. pubescens, of a dirty white or green.

These colors are indeed subject to some final variation, accord-
ing to whether the drying of the bark is effected more or less quickly
by a fire, or by allowing it to remain exposed to the air and sun,
whereby, frequently through rain and dew, the barks again become
moist. The remarkable change of color of the fresh bark always
remains a noteworthy characteristic of the true Cinchonas.

In the color of the bark a serviceable means is presented for the
characterization of the barks individually, or at least for forming
the varieties into groups. The older investigators of this subject,
as also the bark collectors themselves, have, therefore, not improp-
erly referred to these distinctions as: Quina amarilla (yellow),
blanca (white), colorada or roza (red), naranjada (orange), negrilla
(brown), etc. The plates of the works mentioned under numbers
2, 6 and 37 in section XVIII give a very good representation of
the colors of most Cinchona barks.

The Cinchona barks in their structure do not display any more
remarkable peculiarities than many other barks; and that which
imparts to them particular features may be comprised in the follow-
ing statements,

The formation of cork (feriderm) takes place in the primary
bark in the zone of tissue located nearest to the inner surface of
the epidermis. The cork cells of the barks of the true Cinchonas
which occur in commerce are thin-walled, and show the usual tabu-
lar form and radial arrangement (Plate VII, A.C.e). The younger
barks are usually still covered with cork, but in older ones this is
not always the case. Even the older barks of Cinchona succirub-
ra, for example, still occur in commerce with the cork adhering,
while the equally strong stem-barks of C. Calisaya yield to the
formation of bork and do not present the uninjured cork, which, in
consequence of the formation of corky bands in the inner tissue,
is thrown off together with the outer bark. The cascarilleros ap-
propriately designate the shallow trough-shaped bork cavities
which are thus formed as Conchas, on account of their resemblance to
flat mussels. Where they are longitudinally extended and also pos-
sibly coalesce, they present an appearance as though having been
formed by impressions of the fingers. These conchas are present
to the most striking extent in the stem-barks of C. Calisaya.

36 CINCHONA BARKS.

The originally collenchymatous outer bark, situated beneath the
cork, is built up of cells of considerable size, which are more or
less extended in a tangential direction (Plate VII, A. C. 0). The
uniformity of this tissue (without considering the interior cork for-
mation) is thereby interrupted, in that its often coarse, porous cells
become, either singly or in large numbers, sclerotic. Such stone-
cells (Plate VII, C. k) are, in the dried bark, either empty or filled
with a crystalline powder of calcium oxalate, or contain a reddish-
brown, solid, occasionally granular substance, which, without suffi-
cient foundation, has been designated as resin. The stone-cells
(sclerotic cells) vary in their form without regularity, so that it must
be regarded as superfluous to distinguish them as cubical cells, as
spherical, or upon the transverse section tangentially extended
stone-cells. A discrimination according to their contents, as crystal-
cells and resin-cells, is likewise of no greater importance. In the
direction of the axis, the stone-cells of the Cinchona barks exhibit
no considerable extension. They appear in the bark, either scat-
tered singly or united in groups, but never representing actually
closed circles of large dimensions, as in so many other barks: ¢. g.,
that of Guaiacum officinale,* Quassia amara,? and Strychnos Nux
vomica.? In many Cinchona barks, the stone-cells are uniformly
wanting: e. g., in the Calisaya and the red bark; in others they
occur sparingly, and in many they are found abundantly, and also
in the bast, as, for instance, in Cinchona latifolia,

On the boundary of the bast, but always only on the inner side
of the parenchyma of the outer bark, isolated ducts of very con-
siderable size are frequently observable, which, upon a trans-
verse section (Plate VII, A. p), present a circular or tangentially
extended outline, and in circumference, but not in the thickness of
the walls, surpass the neighboring parenchyma cells. In the larger
diameter they frequently attain over 200 micromillimeters (C. succi-
rubra), in C. boliviana, even more than 500, but are also often
diminished to less than from 40 to 50 micromillimeters.

On a longitudinal section, these mk tubes or lacticiferous ducts
do not appear extended in length; their obtuse ends are closed,
and they are usually isolated, or from two to three arranged in a
row before the last bast-wedges, without, however, having any defi-
nite relation to the latter, Ona transverse section, the lacticiferous
ducts therefore form a but slightly regular, sometimes repeated,

* Compare Fliickiger, Pharmakognosie, second edition, 1882, p. 453.

* Ibid, p. 459.

* The same work, first edition, 1867, p. 427. Moller, Anatomie der Baumrinden, 1882,
pp. 162, 419.

ANATOMICAL STRUCTURE. 37

and often approximately closed circle. In cases where they remain
small, they may be easily overlooked when the sections are softened
with potassa instead of the less destructive alkali ammonia.

According to Karsten the lacticiferous ducts occur in the
youngest branches of all or nearly all Cinchonas and their nearest
allies, but in individual species they remain very narrow and soon
become quite insignificant ; a change which is also in part thereby
effected, that in their interior a new formation of parenchymatous
cells takes place.*

Although these lacticiferous ducts can scarcely be considered as a
peculiarity of individual Cinchonas, they are, indeed, wanting in some
commercial barks, and are retained in a state of preservation in
others, in so far as the entire outer bark has not become complete-
ly destroyed by the formation of bork.

The lacticiferous ducts may, moreover, according to Weddell,’
be best traced in the medulla of living branches, especially near
the nodes of young axes.

More important points of discrimination are afforded by the bast
of the Cinchona barks (Plate VII, B. C. v), which, in consequence
of the removal of the bork, represents exclusively some varieties
of commercial bark (Plate VII, B). It is intersected by medullary
rays (Plate VII, v), which radiate from the wood in 3, or at most 4
parallel rows (large medullary rays, chief medullary rays), The
cells of the medullary rays are almost invariably larger than those
of the bast parenchyma, and increase toward the exterior in width
as also in the number of the individual rows. In the tissue of the
medullary rays, especially in the outermost layers, isolated cells
often become thickened to stone-cells (Plate VII, C); still more
frequently many contain a crystalline powder, and also without
becoming lignified. Sosa :

The bast contains as its most prominent constituent spindle-
shaped fibres (Plate VII, sc), which are extended in the direction
of the axis, and whose walls become thickened at a very early
period. When the cells become thickened to a less extent, and do
not terminate in a point, they are distinguished as staf-ced/s, or
staff-shaped stone-cells. |

In the younger barks of most species the bast-fibres are found
sparingly scattered, but with increased age they multiply consider-
ably in number, lose their cavity almost completely, and press back
_ the surrounding bast-parenchyma quite strongly. On a transverse

1 ee Vogl, Chinarinden des ‘Wiener Grosshandels, p. ia: De Bary, Anatomie,
Pp. 558. : : o 3
2 Hist, nat. des Quinguinas, Tab. I. Fig. 26.

388 CINCHONA BARKS.

section the fibres appear in distinct and very neatly arranged
layers, which are traversed by fine canal-like pores;* in outline
they are spherical or angular, frequently somewhat extended in a ra-
dial direction, and the cavity mostly confined to a dark fissure or a
point. Since the bast-fibres terminate at the ends in a point, which,
however, is not actually sharp, the dimensions of a transverse section
at different heights is subject to variation. The larger diameter of
the strongest fibres attains to about 200 micromillimeters, but is
usually only one-half or one-third of this size.

On a longitudinal section the bast-fibres of the Cinchonas are
seen to be proportionately shorter than the corresponding cells of
many other barks, although their length is within the limits of ordi-
nary measurements, and easily amounts to from 2 to 3 millimeters,
They present themselves, in so far as they do not stand completely
isolated, with their pointed ends wedged above and between each
other, and never transversely connected, but rather always either
simply curved, or at the most, sabre-shaped; they are, however,
mostly spindle-shaped. In consequence also of their shining yellow
or yellowish-red color they may readily be observed in the other
tissue.

The transverse sections of strong bast-fibres are very hand-
some objects in polarized light, in that they display a black cross,
and besides, with only slightly thicker sections, vivid colors in the
quadrants,

The finer spiral rudiments of their structure can only be observed _
when the bast-fibres have first been boiled in hydrochloric acid, and
subsequently placed in an ammoniacal solution of oxide of copper.”

The bast-fibres of the true Cinchonas are characterized by their
considerable thickness and lignification, as also by their simple form
and pointed ends. Although in the beginning making their appear-
ance in an isolated form in the youngest axes, they afterward
arrange themselves in various ways, so that the individual species
of Cinchona are also to a certain extent characterized by their
peculiarities in this respect.

The bast of the Cinchona barks, 7. ¢., that of the true Cinchonas,
does not appear distinctly reticulated. Even where lignified bast-
fibres occur in large numbers, they do not form groups of large
dimensions, nor branched, long and compact bundles;? and espe-

_ 1 De Bary, Vergleichende Anatomie der Vegetationsorgane, 1877, Pp. 139.
_ _ # Compare Hofmeister, Verhandlungen der sitchs. Gesellschaft der Wissenschaften
: no - (1858), p. 32; Fliickiger, Grundlagen der pharm. aarenkunde, ore, p. oh

_ * Compare De Bary, Anatomie, p. 544.

LOCATION OF 7HE ALKALOIDS. 39

cially at the point of the bast-wedges, on the boundary of the outer
bark, they occur only very much scattered (Plate VII, A).

The steve-tudes in the Cinchona barks of commerce are usually
very much collapsed, and therefore can only be isolated with con-
siderable difficulty.

While in the young barks the soft bast predominates, this pro-
portion becomes gradually changed in favor of the greater or less
development of the sclerotic fibres. The bark of the same species
must, therefore, in accordance with its age, present a very dissimi-
lar appearance, and consequently afford but a deceptive criterion
for the purpose of diagnosis, even when within certain boundaries
the specific peculiarity is maintained.

The barks of the individual Cinchonas present some prominent
distinctions, especially with regard to the more or less considerable
number of stone-cells, as in some barks such sclerotic cells are en-
tirely wanting. The barks furthermore differ from each other with
relation to the arrangement of the bast-fibres. The considerable
thickness, the simple, spindle-shaped, compact form, and the not
very large number of these bast-fibres, impart to the Cinchona barks
a definite character, which is not possessed by the barks of the
most closely related species that have as yet been examined.
That, however, intermediate representatives are not wanting, is
illustrated by the “Cinchona rosa,” as described on page 49.
Among themselves the Cinchona barks display, indeed, great uni-
formity; and in many figures, such as are given by Berg’, for ex-
ample, no decided characteristics are rendered prominent, when
they are compared with each other,

SECTION VIII.
CONTENTS OF THE TISSUE. LOCATION OF THE ALKALOIDS.

Most of the cells of the true, as also of the false Cinchona barks
which are not lignified, or not completely so, with the exception of
those of the cork cambium and the crystal ducts, are so abundantly
filled with coloring matter, which also penetrates the walls, that
their other constituents, as also their structure, is only plainly per-
ceptible when the coloring matters are to some extent remove
an operation which is best effected by ammoniacal alcohol. Even
the cork frequently contains Cinchona-red, and in the innermost,

1 A description of them is given by Miller, Baumrinden, pp. 132, 138. _ :

2 In the work mentioned under Section XVIII. With regard to the peculiarities of
structure of the Cinchona barks in comparison with other Rubiacee, see Méller, Baum-

vinden, pp. 132, 138.

40 CINCHONA BARKS.

still living layers, small starch granules. The same are also found
in the parenchyma of the bark itself, although not very abundantly.
The outermost layers of young barks contain, moreover, also
chlorophyll granules.

The already mentioned, extremely small and slightly developed
crystals of calcium oxalate, are deposited here and there in the
parenchyma of the true Cinchonas, so that all the cells containing
crystals by no means possess lignified or even only thickened
walls; the stone-cells enclosing oxalate are altogether of even less
frequent occurrence. Larger, often well developed crystals, are
contained in the barks of those trees which are related to the Cin-
chonas, as in the Cinchona cuprea, and, as it appears, also usually
in greater abundance. In others, vertical rows of cells containing
crystals are found in the bast, while in the Cinchona barks these
only occur isolated.

In addition to these universally distributed substances, the
peculiar constituents of the Cinchona barks do not admit of direct
observation by means of the microscope.

Oudemans (Aanteekeningen, etc., of the Pharmacopoeia Neerlan-.
dica, 1854 to 1856, p. 221) had already observed the occurrence
of crystals in Cinchona Calisaya and Cinchona rubra, Howard, in
1862, in the Nueva Quinologia of Pavon (Plate II of the micro-
scopic figures), and in 1870, in the first part of the “East Indian
Plantations,” figured crystals which exhibit themselves in the paren-
chyma of Cinchona barks when thin sections of the same are
warmed for a moment with caustic alkali, and the latter removed
as speedily as possible. Howard declares these crystals to be the
chinovates of the cinchona bases, and considers that they are already
deposited in a crystalline form’ in the respective barks, as, for
instance, in Ledger’s Calisaya bark, where these crystals are said
to be already visible without further treatment of the section. By
the examination of a bark kindly furnished me by Howard, I was
unable to convince myself that such crystals were originally present
therein; they presumably consist of the alkaloids which have been
liberated by the action of the alkali.

Through my investigation, as also that of Miller, it is known
that the alkaloids are located in the parenchyma of the Cinchona

barks and not in the bast-fibres. Carles* has likewise confirmed
these observations.

* Kerner finds the chinovates of the cinchona bases to be uncrystallizable.

? Wiggers-Husemann’s Fahresbericht der Pharmako oste, etc., 1866, p. 82;
Quinology of the East Indian Plantations, 1869, p. 33. i i 1 eps eles
* In Pringsheim’s Fahrbiicher Sir wissenschaftliche Botanik, 1866, p. 238.

* Fournal de Pharmacie, 16, (1873), p. 22.

VARIETIES OF CINCHONA BARK. 41

SECTION IX.

VARIETIES OF CINCHONA BARK.

If the anatomical relations of the true Cinchona barks are sum-
marized, it is manifest that they owe their peculiar character as well
to the totality of the former as also particularly to the nature and
position of their lignified bast-fibres. This appears very prominent
in distinction to the other Cinchonee which are so closely connected
in the system, the structure of which, however, has as yet only been
described in a few instances.*. In many of the latter, the lacticife-
rous ducts are much more perfectly developed, and the sclerenchyma
forms likewise, even in the outer bark, large and often vertically
extended bundles; the bast, however, deviates most from the above-
described type of the Cinchonas, as has already been shown on
page 38. The bast-fibres of many of the false Cinchonas are thin,
by far not completely lignified, on a transverse section exhibiting a
significant cavity, and usually roundish. On a longitudinal section
they display considerable length, and as strong, often net-like,
transversely connected fibres, impart to the entire tissue a coherence
which the short, simple fibres of the Cinchonas are not able to give.

In many of the false barks, the parenchyma of the bast also
performs a more significant part, whether it be that its regularly
arranged tangential zones, alternating with fibre-bundles, cause a
reticulated appearance, or whether the inner half of the bast is built
up, to a largely predominating extent, of parenchyma. The tissue
of these barks also receives hereby far greater firmness and tenacity
than the Cinchona barks. :

These distinctions are then also perfectly adequate to discrimi-
nate between the barks of the Cinchonas and those of the other
allied genera. : eo |

As in many barks, the transverse fracture of the Cinchona barks
is also subjecg to variation in the inner and the outer portions.
The latter, consisting of the cork and the parenchyma of the outer
bark, break uniformly and short, in so far as dead portions of the
bast are not, through the formation of bork, drawn into the ex-
ternal coating or periderma. , 2

In opposition to this uniform, quite smooth, so-called corky
fracture, the inner layer of stronger barks docs not present an _
even fractured surface, but there project therefrom isolated, com- _
pact bundles of fibres, which are extended in the direction of the axis. —

1 Compare Berg, Chinarinden der pharmakognost. Sammlung in Berlin, 1865, p. 39;
Fliickiger, Fahresbericht der Pharmacte, 1871, p.95; Vogl, Fatsche Chinarinden, 1876, ;

42 CINCHONA BARKS.

Weddell was the first to emphasize that the appearance of the
fracture of the Cinchona barks is subject to variation, according to
the size and the arrangement of the bast-fibres. To these short,
not interlaced fibres, the Cinchona barks owe particularly the great
brittleness.

The root-bark of the true Cinchonas appears to possess in
general the structure of the bark of the stem or branches, and
particularly to be much inclined to the formation of bork.

Among the chief varieties which hitherto came from South
America, and which received the preference for pharmaceutical
applications, the following are to be particularly mentioned:—

I. CINCHONA CALISAYA.

After Jussieu had already traversed the region of the Cinchona
Calisaya, Rubin de Celis, in 1776, and Thaddaus Hanke,’ in 1791,
called attention to the value of their bark, so that the latter, since
about the year 1789, acquired ever increasing significance, although
the tree itself was first made known by Weddell (see page 16).
In commerce there is found the entire bark of the branches, in the
form of quills, as also the flat stem bark deprived of the bork, and
indeed :—

(a) The former under the names of Cortex Cinchone (Chine)
regius, convolutus, Cinchona (China) calisaya cum epidermide, Calt-
saya tecta s. tubulata; Quill Calisaya; Ger., Gerollte or bedeckle
Konigschina; Fr., Quinguina Calisaya roulé. \t forms quills 3
to 4 centimeters (114 to1¥% inches) in thickness, which are mostly
rolled inward at both edges (double quills), of a dark grayish-
brown color, or whitish, and having coarse, irregular, longitudinal
channels and furrows, which, however, in general are to a certain
extent uniformly arranged, and intersected by deep transverse
fissures, which frequently extend over the entire periphery. Re-
ticulations with elevated edges and a usually somewhat more finely
furrowed surface are hereby formed, which readily become detached,
and still permit the recognition of their outlines onthe outer sur-
face of the cinnamon-brown inner bark. The inner surface is of a
brownish-yellow color, and accurately striped in a vertical direction
by the bright bast-fibres; the fracture is purely fibrous, but exter-
nally darker and shorter.

? A Spanish marine officer, —

? Hanke was born in the year 1761 at Kreibitz in Bohemia, and in 1 ‘ue to South
_ America with the Spanish expedition under Malaspina. He located, Agiss at Cocha-
—— ao sie Papen — the distri vo where Cinchona bark is collected, and

ied in 1817, upon at Buxacaxey, in the province of Cochab: . ,

_ Geogr. Mittheilungen, VI (1867), 264. © . ens. “nes a

VARIETIES OF CINCHONA BARK. 43

The outer bark exhibits practically no stone-cells or only a few
isolated ones, but contains a single or double circle of lacticiferous
ducts, which, however, soon disappear.

The bark of the Indian Calisaya Ledgeriana (see page 17), in
consequence of its much higher percentage of alkaloid, now fur-
nishes a complete substitute for the American bark. Many of the
varieties formerly known as Loxa Bark, and derived from different
Cinchonas, are especially distinguished from the bark of the twigs
of Calisaya by the less reticulated outer surface.

(b) The bast of the stem as Cchona (China) regia plana,
Cinchona (China) regia sine epidermide; Flat Calisaya; Ger.,
Flache, platte, unbedeckte Konigschina; Fr., Calisaya plat.

Flat pieces, of a foot or several feet in length, often nearly 2
decimeters (8 inches) in width and from 5 to 15 millimeters (14 to
54 inch) in thickness, and of that particularly handsome pure color
which is designated as a type of the yellow varieties of Cinchona ;
indeed, the approach to a reddish-yellow tint is often scarcely per-
ceptible. The outer surface, by the action of the air, is frequently
darker, at least in spots, and in consequence of the conchas (see
page 35) more or less, often to the highest degree, irregular; the
inner surface does not always exhibit parallel stripes, as in the
barks of the branches, but is often wavy. In this case, the bast
bundles of the different layers occasionally separate from the frac-
tured surface in a diverging direction. This variety of bark is highly
characterized by its soft tissue; even with the finger-nail one can,
without effort, separate the pointed fibres, which readily penetrate
the skin.

On the edges of the conchas there are,as a rule, only a few easily
detached bork-scales. The bast, of which, without consideration of
the interior cork bands, the bark alone consists, displays sometimes
more and sometimes less plainly radial, occasionally also almost
tangential, rows of fibres. Here and there from 2 to 4 of these
rows come in direct contact, but otherwise they always occur sepa-
rated by the abundant parenchyma. ae

The flat Calisaya bark from Bolivia, which until within a few
years maintained a high character, has latterly occurred in com-
merce with a very much diminished percentage of alkaloid. It
was occasionally confused with the bark of a south Peruvian spe-
cies, Cinchona scrobiculata Humboldt et Bonpland. Their uncov- —
ered bast-plates resemble to a high degree those of the flat Cali-
saya, but are distinguished, however, especially upon being moist-—

1 Figure in Humb. et Bonp., Plantes éguinoct, t. 47; also Weddell’s Hist. nat. des
Quinguinas, Plate VII. ; S

44 : CINCHONA BARKS.

ened, by their plainly reddish and often fiery color, and by greater
compactness and fibrous fracture. The parenchyma of the outer
bark is rich in stone-cells, and contains also in younger pieces lac-
ticiferous ducts. No other cinchona shows a so plainly radially
arranged bast. The fibres of the latter form upon a transverse
section, long, mostly one-lined radial rows, in which often upon large
spaces only here and there a small parenchyma-cell occurs. The
bast-fibres are present in such large numbers that in the inner
layers they predominate to a considerable extent.

This bark, which appears to contain regularly only a small per-
centage of alkaloid, finds its way into commerce under many
designations in the pure state, as also mixed with Calisaya. Thus
in Cusco it is commonly termed Cascarilla colorada or Cascarilla
de Santa Ana ; in Europe it is known as light Calisaya, reddish
Calisaya, Carabaya, or red Cusco bark, Cinchona (China) peruvi-
ana, and Calisaya fibrosa.

In the illustrations of the bark, the coloring by Delondre and
Bouchardat, Plate 3, although not absolutely accurate, is much more
correctly reproduced than in Weddell’s Plate XXVIII, where the
color agrees altogether too closely with that of Calisaya.

II. BARKS OF CINCHONA LANCIFOLIA.

The cork is at first grayish, afterwards whitish or yellowish,
glistening, soft and readily exfoliating. The bast is yellow or
reddish-yellow; the bark parenchyma is still in part retained, even
in the quite strong, flat trunk barks of as much as 1 centimeter
(36 inch) in thickness, as they usually occur in commerce: for it
is only at a late period that the true formation of bork takes place.
The outer bark is distinguished by a number of tangentially ex-
tended stone-cells, which often forma nearly connected layer (Plate
VII, C). The moderately thick bast-fibres are in single or double
radial rows, connected at intervals, and having an occasional tend-
ency to a tangential grouping in the interior. In the bast there are
numerous staff-cells, and not unfrequently there are also the same
stone-cells as in the outer bark; the latter form of cells occurs quite
as frequently in the medullary rays.

The bark breaks with a fine splintery, sometimes short and some-
times long fracture, and is found in different varieties, which, by sub-
ordinate characteristics, deviate somewhat in appearance and struc-
ture. It is nevertheless possible that they may be referred to

: ae several Cinchonas.
In this place belong the varieties of cinchona designated as flava

a : fibrosa, then the Calisaya of Santa fe de Bogoté, OQuina anaranjada

VARIETIES OF CINCHONA BARK. 45

of Mutis, the Cagueta bark of the English, more correctly Caqueza
(after the place of this name not far from Bogota), the Carthagéne
ligneux of the French, etc. Many barks of Cznchona rubiginosa of
former times were derived likewise from C. lancifolia.

Karsten, as also the Consul Rampon,* whose opinions are
based upon personal observations at the place itself, give promin-
ence to the fact that C. lancifolia, which is botanically so variable,
furnishes also, indeed, barks of very different appearance. The best
varieties are called in New Granada, columdbian ; the less valuable
bear the name of Carthagena Barks.

III. RED CINCHONA BARKS, FROM CINCHONA SUCCIRUBRA.

The bark of small, one and-a-half year old trees, which in its moist
condition is only 1 millimeter (4 inch) in thickness, e. g., from
Hakgalle in Ceylon, consists only to the extent of % of the bast
layer, wherein entirely isolated or groups of from 2 to 3 bast fibres
occur, which are mostly already lignified. The boundary of the
outer bark is designated by wide lacticiferous ducts, which, occur-
ring usually to the number of two before a bast ray, represent a
very interrupted circle.

Even by a thickness of about 5 millimeters (; inch) the rela-
tion of the two layers of bark becomes so altered that the bast
begins to predominate, and deposits its beautiful dark red fibres in
very large numbers. The latter are in interrupted radial rows,
separated by narrow strips of quite small-celled parenchyma, and
toward the interior by a tangential arrangement, affording also at
the same time, in places, an almost reticulated appearance.

A multiplication of the lacticiferous ducts is not prominent, but
they become gradually enlarged, and by the development of the
bark remain for a long time intact, as it is only at a late period
that the formation of bork occurs. Pieces of bark over 12 milli-
meters (% inch) in thickness (in their dry condition), still display
lacticiferous ducts.

The ejection of the peridermis takes place with much greater
difficulty than with C. Calisaya, so that even strong trunk barks of
the red cinchona still bear a firmly adhering, more grayish-black
than red external coating, even by a well defined development of
the interior cork. ; "

According to Von Bergen, the Red Cinchona was already dis- _
tributed in North Germany at the beginning of the eighteenth —

century, and Condamine makes mention of it, in the year 1737,as

the best Cinchona; it may, e. g., with reference to the description
| 1 In Planchon (Title under section xviii) 95.

46 CINCHONA BARKS.

of Mutis (p. 48), remain undecided whether it was always really the
bark of C. succirubra.’ The formerly quite extensive exports of fine
trunk barks of this Cinchona from Guayaquil have long since
considerably decreased. On the other hand, branch barks of the
same from Ceylon and from the peninsula of India, as also from
the other Cinchona plantations, are brought in ever increasing
amounts into commerce.

The American Red Cinchona, in accordance with Howard's
proposition, was referred in 1857 by Klotzsch and H. Schacht’ to
C. succirubra.

For the classification of the Cinchona barks the color was adopt-
ed asa principal characteristic, until the study of their anatomical
structure appeared in the foreground. It may be accepted that
the fundamental color of the barks of one species does not remain
the same at all periods of life; C. succirubra, e. g., shows that the
special color first appears with absolute definiteness at an advanced
age. Younger barks of most species are, as a rule, covered with
a grayish-white or sometimes brownish or nearly blackish cork,
which only in the extremes of its color or in the form of its outer
surface is able to afford points of discrimination. Still more indefi-
nite and predominatingly brownish is the color of the inner tissue,
so that mixtures of the most different quill barks taken from the
twigs or younger trunks bear the general name of Cortex Cincho-
ne (Chine) fuscus. As of equal signification the usually less ap-
propriate designation of Cortex Cznchone (Chine) griseus seu
palhdus is applied, with reference to the external coating, as also
the appellations, quite common with the French, of Ouinguinas gris
ou brun, and the English expressions, Pale Cinchona Bark, Gray
Bark.

As the most important of the brown varieties, is to be mentioned
the Cinchona from the district of Huanuco, in central Peru, which
is exported by way of Lima, and named after these two cities. It
usually consists of quills, which, after being moistened, are from 1
to 2 centimeters (34 to 34 inch) in circumference and from 2 to 5
millimeters (;, to ~ inch) in diameter. Its grayish-brown, and in
~ general quite bright external surface, is somewhat furrowed longi-

tudinally, provided with transverse fissures, which are mostly not
very deep and do not extend over the entire periphery, and often
still covered with whitish cork. The inner surface is of a bright

? Compare also therewith, Murray, Apparatus medicaminum, VI (1792), 44.

° * “On the Origin of the Red Cinchona Bark of Commerce,” Abhandlungen der Akad-
_ emie der Wissensch, zu Berlin, 1858, pp. 51-78. :

VARIETIES OF CINCHONA BARK. AT

cinnamon color, and frequently finely sprinkled with white, in con-
sequence of the cells of the medullary rays, which contain oxalate.
A transverse section shows directly beneath the outer bark a so-
called resin ring.

A species belonging in this category, namely, the bark of Giu-
chona nitida Ruiz et Pavon, which is designated as Pala de gallina-
z0, affords an excellent example of the fantastic names with which
the Cascarilleros provide the Cinchona Barks. In consequence of
the corky warts (lenticels?), asalso of the Sphaeriaceze, whichare found
upon this bark as well as upon many others, there is formed a pe-
culiar delineation of the outer surface, which in Peru is designated
as “vulture claws,” pata de gallinazo. Gallinazo refers in Lima to
the carrion vulture, Cathartes foetens... Such names are now best
cleared away by the innovation of the Dutch Government, which
consists in attaching to the larger packages of Javanese barks the
results of the analysis and the designation of the mother plant.

In former times the Huanuco variety consisted chiefly of barks
of the Cinchona nitida, which grows in large amounts by San
Cristoval de Cuchero or Cocheros, not far from Huanuco. The
barks of this district were made known since 1776, by Francisco
Renquifo and Manuel Alcarraz, and then by Ruiz, Pavon and Dom-
bey,? and finally toward the end of the century introduced into com-
merce by merchants from Lima, as gray bark of Huanuco.

As Loxa or Loja Cinchona, barks are or were exported, which, in
distinction to the preceding variety, are predominatingly of a dark
brownish color, have a more gray than whitish coating, and, be-
side longitudinal wrinkles, exhibit numerous, somewhat distant,
transverse fissures, The Loxa bark consists mostly of quills having
a maximum circumference of 1 centimeter (34 inch), and only
I to 2 millimeters (,; to yj; inch) in diameter, and is frequently
abundantly beset with lichens. A sharp transverse section of the
better sorts of Loxa bark exhibits the glistening “resin ring.”

As has been previously mentioned (p 19), the district of Loxa
furnished the first Cinchona barks. At the time of the Spanish
sovereignty the most select specimens of the same, a yellowish
and areddish variety, Cascarilla amarilla del Rey and Cascarilla

colorada del Rey, were retained for the Spanish Court, and bore for

* Markham, Pritchett, B/ze Book 1863, 129, 125. I was told, however, by Mr. Spruce,
in August 1867, that the expression Pata de ga/linazo refers to the fracture of the bark. -

? Figure in Weddell, T. 10; Howard, NV. Quinologia, T. 20. ‘ as

* Joseph Dombey was born in the year 1742, at Macon, and went to Peru with Ruiz
and Pavon in 1777; he returned to France in 1785, but departed again for America in
1793, and died in 1794 at Montserrat—Cap. Ltudes biogr. pour servir a& L hist. des
Sczences, II (1864); compare also my Pharm. Chemie, pp. 611, 890. .

48 CINCHONA BARKS.

a long time the name of Cixchona (China) coronalts, which is still
retained in the English “Brown Bark,” Ger., Konigschina, while
the adjective regz#s or regia has been transferred to Calisaya. To
obtain this original Brown Cinchona, at the time of Humboldt’s
residence in South America, very young trees were stripped, of
which from 800 to 900 were required in order to furnish the
small amount of 110 hundred-weight of bark, which the Court
required,

This entire class of the predominatingly brown South American
barks comprised several sorts, the discrimination of which reposes
upon such external characteristics as deprive them of exact scien-
tific definition.

The circle of the officinal Cinchona barks was confined there-
with, on the one hand, to the medium or younger quills of a few
species, in that, for the accustomed sorts, as above shown, in the
course of time the same Cinchonas were not always collected,
and on the other hand to the red-trunk barks and the bast-plates
of Calisaya.

All the remaining sorts which occur in commerce, of which here
also mention is occasionally made, and still others, are of interest
only for their applications in chemical industry, and not for phar-
macy.

The plantations of the Cinchonas in India, Jamacia and other
districts furnish meanwhile mostly still younger barks, in which
very decided peculiarities are wanting. At the present day more
importance must be attached to the determination of the amount
of alkaloid of these barks than to their external appearance.

SECTION X.
THE SO-CALLED SPURIOUS CINCHONA BARKS.

Before the alkaloids were known, various other barks found
their way into commerce, in part without disguise, as a pretended
substitute for the medicinally active Cinchona barks, and in part
mixed with the latter, although their inferior value was perceived
at an early period. Among these false or spurious Cinchona barks
the only one until recently of any importance was the hard bark
of Cascarilla magnifolia,' Endlicher (Cinchona oblongifolia Mutis,
C. magnifolia Pavon, Ladenbergia magnifolia Klotzsch, Buena mag-
_nifolia Weddell; it is also probable that Karsten’s Cinchona hete-
_ -rocarpa was nothing else than this tree.) Mutis, in the year 1780,

_ ? Figured in Howard’s NV. Quinol., Tab. 10; Karsten’s FZ. Colomb. Tab. VI.

THE*?SO-CALLED SPURIOUS CINCHONA BARKS. 49

erroneously described the same as Cascarilla roja,* and later, par-
ticularly at the beginning of this century, it was brought in enor-
mous quantities into commerce as Czuchona (China) nova suri-
namensis, although probably for the most part not from Surinam,’
but from New Granada. This stately tree is distributed through
Columbia and Ecuador, presumably also still more widely, and is
known as Cascarilla flor de Azahar. Its small white flowers,
scarcely tinted with red, which indeed by their downy pubescence
approximately resemble the Cinchonas, diffuse a fine orange-like
fragrance. (Azahar designating in Spanish, orange and lemon).

This Cinchona nova also occurred from 20 to 30 years ago under
the name of Cinchona rosea or Cinchona Savanilla,? and even as
Cinchona Valparaiso. It contains no cinchona alkaloid, as one
may easily become convinced by means of Grahe’s test (see p. 68),
and is altogether free from alkaloid At the present time it is not
found in commerce.

From an anatomical point of view this bark is positively distin-
guished from the barks of the Cinchonas, especially with regard to
the obtuse ends of the bast-fibres and the remarkable abundance of
sieve tubes. The bast-fibres of the “Cinchona (China) nova”’ are
much more numerous, thinner, longer, and not so completely ligne-
fied. The figure of the transverse section’ agrees very nearly with
that of Cinchona cuprea (see Plate VIII). When, however, at some
time the barks of numerous other Cinchoneze shall be compared
therewith, there is no doubt but that intermediate forms will be
found. Such an one, e. ¢., is to be observed to a certain extent in
the beautiful rose-red, feebly bitter bark of Condaminea tinctoria
D. C.,° which contains not a very large number of strong bast-fibres,

1 See page 17, by Calisaya Ledgeriana.

2 Murray, Apparatus Medicaminum, V1, 181, 222, was indeed, in 1790, in possession
of a specimen of this bark from Surinam. It was known that it did not possess the me-
dicinal power of the true Cinchona, Later communications relating to this worthless
bark are contained in the Fahresbericht der Pharm., 1857, p. 40, and 1862, p. 42.

3 Archiv. der Pharm. 116 (1851) 374, and therefrom in the Fahresbericht, 1851, 52.
It is very remarkable that this bark was named by some drug dealers Cinchona from
Valparaiso. aes

4 Hesse in Fehling’s Nenes Handworterbuch der Chemie., Il (1875), 531-

5Berg, Chinarinden, Plate X, 27.

6 Synonyms: Cinchona Jlaccifera Pavon, Macrocnemum tinctorium — Humboldt,
Bonpland et Kunth. The genus Condaminea, established by De Candolle, is distinguished
from the Cinchonez by the fleshy corolla, the conical capsule and the wingless seeds.
Tafalla (section 17), had already called attention to the bark of this tree, which, in the |
domain of the upper Orinoco or Paragua furnishes to the natives a red color. It is also
probably with regard to this that it has received by the natives the popular designation of
Paraguatan bark. After the bark, through Humboldt, had become known to a certain
extent in Europe, small quantities of itappear occasionally to have been brought into
commerce. Virey, ¢. g., stated in the Yournal de Pharmacie, XIX, (1833) P 199, _

50 CINCHONA BARKS.

reminding of those of Cinchona bark. The fibres of the Conda-
minea are, however, thicker, less brittle, of very unequal length
and thickness, and mostly provided with a considerable cavity.
As much as this bark" is separated from the true Cinchona barks
in its appearance, it nevertheless, by reason of these bast-fibres,
approximates more closely to the latter than, e. g., to the Cinchona
cuprea,

SECTION XI.
CINCHONA CUPREA.

The remarkable bark, which I designated in the year 1871 as
Cinchona (China) cuprea,? has received much consideration. — It is
characterized by a peculiar color, which, on the outer surface,
reminds of somewhat rusty copper utensils. It was emphatically
set forth that I did not compare the appearance of this copper-
colored bark to the color of the bright metal.

After the communications of Hesse and myself in regard to the
Cinchona cuprea (1871), nothing was heard again for a time of this
bark. It was first at the end of February, 1880, that Mr. oe
Howard informed me that it began to appear, unmixed, in larger

that Paraguatan bark had been received at Cadiz: O. Henry (ibid, p 201) found it to be
free from cinchona alkaloids, It is furthermore described in Guibourt's Flistoire natu-
relle des Drogues simples, 11 (1869), p 185. Condaminea tinctoria, moreover, grows not
only in the northeastern part of South America, but also in Chili and in the Argentine
Republic. Mr. Stuckert, an apothecary of Basel, brought the bark of the same from

Tucuman in 1880, under the name of Cinchona ( China) rosa,

* The longitudinal section shows, however, great distinctions in comparison with Cin-
chona barks ; the fibres of the Condaminea bark are much less regularly spindle shaped.
In the beautiful red decoction which fresh “ Cinchona rosa” affords, the coloring matter
is only suspended, not properly dissolved. When this is removed by filtration through
bole or charcoal, a fluorescent filtrate is obtained, the bluish reflex of which is not destroyed
by hydrochloric acid, and therefore cannot proceed from quinine. This remarkable
— cy does not afford the red tar (p 68); nevertheless it is said to contain a trace of

aloid.

Very similar to the “ Cinchona rosa,” and perhaps identical therewith, is also the so-
called Arariba bark, which Rieth describes in Liebig’s Annalen, 120 ( 1861), p. 247, and,
in accordance with the statement of Martius, refers it to Avariba rubra, which is entirely
unknown to me. _Its diagnosis will be found in C. Fr. Ph. von Martius’ paper, entitled
“Zur Kritik des Gattungscharacters von Cinchona,” as contained in the S¢tzungsberichte
der Miinchener Akademie, Il (1860), Pp. 323. Rieth found in the bark the crystallizable
Arabine, C,,H, N,, the only solid base which is free fron oxygen. Vogl, on page 17 of the
commemorative essay mentioned under section 18, No. 35 of this work, describes the
same bark as Cinchona (China) von Cantagallo, and Miller, Baumrinden, 1882, gives
on page 142 a good figure of a magnified transverse section of the same.

2 Vorwerk’s Neues Jahrbuch fiir Pharmacie und verwandte Facher, XXXVI (Speier,
1871), p 296, and therefrom in Wiggers-Husemann’s Yahresberichte der Pharm, 1872, p
132. Mr. J. E. Howard forwarded to me at that time a good specimen of Cinchona
cuprea, which, as early as 1857, had come under his observation among other barks in
the London market. He had also already found it to contain quinine, although he had
not published anything concerning it. Vogl has likewise considered the Cinchona
Cuprea in his commemorative essay, p 98, mentioned under section 18 of this work.

CINCHONA CUPREA. 51

quantities in the London market, and was eagerly purchased. The
first imports, according to Paul,‘ occurred as early as June 1879,
and soon thereafter, notwithstanding the unusual appearance of the
“Cuprea,” its value was determined to the effect that it contained
about 2 per cent. of sulphate of quinine and only a small amount of
the associate alkaloids. De Vrij obtained from the same altogether
as much even as 5.9 per cent. of alkaloids (Letter of September 23,
1$82). In May, 1880, large supplies of this bark were already to
be seen in London,’ and the subsequent imports directly assumed
unsuspected dimensions.

Cinchona cuprea occurs in quite flat or channeled pieces, more
rarely in quills of scarcely half a meter (20 inches) in length, and
at the most from 5 to 7 millimeters (+ to } inch) in thickness ; but
by far the predominating amount consists of small fragments, and
conveys altogether the impression that it can only be derived from
a tree of small dimensions. The light brown, longitudinally wrin-
kled or warty cork is usually scraped off, so that the smooth outer
surface is formed of the tissue of the outer bark, to which pertains the
previously mentioned color of copper vessels. The outer surface also
often shows impressions of the incisions of a sharp knife, whichare oc-
casionally but a few millimeters distant from each other, and extend
in a parallel direction, probably for the purpose of removing the
cork, and presumably in order to render prominent the more pleas-
ing color of the inner tissue. This is indeed so peculiar, in dis-
tinction to former Cinchona barks, that it must attract the attention
of any one who has made himself familiar with the appearance of
true Cinchona barks; the copper-colored bark deviates to a still
greater degree from all true Cinchona barks by its great hard-
ness. It is also impossible to confuse it with the Cinchona nova
surinamensis, for the reason that the Cinchona cuprea yields the
red tar of Grahe’s test (p. 68).

Specimens of this Cinchona cuprea were furnished, in 1879, toa
German house (Lengerke & Co.) in Bucaramanga, in the Colum-
bian state of Santander, and were sent by them to New York and
London for the purpose of examination, The favorable result of
the analyses then led to the collection of this bark on a large scale
in the forests of the mountains which, above Bucaramanga, ascend
from the main valley of the Magdalena river to the chain of La
Paz, and form the water-shed between this stream and its tributary,
the Suarez. e se

The tree which furnishes the Cinchona cuprea begins to make

1 Pharm. Fourn. X1 (September, 1880) 259. one ae
2 Pharm. Fourn X (1880), 954.

52 CINCHONA BARKS.

its appearance at elevations of 1600 feet, and the best bark is only
stripped at elevations of from 2200 and 3200, or even as much as
4200 feet, as was reported to me in November, 1881 and in Feb-
ruary, 1882 by Dr. Chas. A. Robbins of New York, from personal
observations. Only a small portion of the root-bark is collected
with the other; and in the wide surroundings of Bucaramanga the
trees of this variety of Cinchona are now quite completely felled.
A to some extent similar bark from other districts, e. ¢., from Tolli-
ma, in about 5° N. lat., in the upper Magdalena valley, has been
proved to contain but little alkaloid. 20,000 colli (serons) of the
same, which were thrown upon the market in 1882, afforded either
extremely little, or atthe most from 0.8 to 1.5 percent. of quinine. The
derivation of this Zo/zma bark has not been determined. From an
anatomical point of view, I find it to agree with common Cuprea
bark; it yielded to Dr. Kerner (1882) 1.778 per cent. of crystallized
sulphate of quinine.

Of late years, and especially until August 1881, the copper-
colored Cinchona has been brought to Europe in ever increasing
amounts. Among the 100,000 col/i (serons), of South American
product, which were imported into London in 1881, there were over
60,000 colli of “Cuprea,” of which, moreover, more than 5500 col/z
found their way to France. Cinchona cuprea, according to its
structure (Plate VIII), belongs to the previously considered false
Cinchona barks, but, in consequence of the alkaloids which it
contains, forms a very remarkable exception. The cork is formed
of thick-walled cells (Plate VIII, e. f.), which are distinguished in
the most striking manner from the much wider, and always delicate-
walled, tabular cells of the cork of true Cinchonas (Plate VIII, A.
C.e.) This fact is the more remarkable, since the bark of Remijia
Hilarii, for example, appears to possess delicate-walled cork cells.
Furthermore, the largest part of the tissue of Cinchona cuprea is
seen to have become converted into sclerenchyma. In the outer
bark (0) already, there are numerous groups of unelongated
sclerotic cells (k) interspersed ; and on the boundary of the bast
there are found isolated lacticiferous ducts (p), which, indeed, are
wanting in very many pieces. The bast consists toa predominating
extent of thickened, simple, somewhat short, unpointed fibres (s),
which, therefore, when observed longitudinally (Plate VII, sr).
deviate entirely from the bast fibres of true Cinchona barks. Only
the staff cells, mentioned on p. 37, are similar to the fibres of Cin-
-chona cuprea, The bast of the latter contains, moreover, shortened
sclerenchyma cells, as well as the outer bark. It is only in the

* Miller, Baumrinden p. 137 (Remijia Vellozii).

CINCHONA CUPREA. © 53

youngest bast layers that sieve-tubes and parenchyma predominate ;
and here particularly, although also in the outer bast, crystal-cells
(x) are present, in which finely crystallized oxalate is deposited.
The bast shows accordingly (Plate VIII) a distinct separation into
an outer zone, rich in sclerenchyma, and an inner parenchymatic
zone, containing fewer fibres, and particularly a less number of
stone cells. The medullary rays of the bast are but narrow.
The by far predominating sclerenchyma is the cause of the
remarkable hardness of this bark, which, therefore, in London,
was also named “hard bark.” It is, furthermore, characterized
by the red coloring matter, which penetrates the entire tissue so
abundantly that it is almost impossible to decolorize it, e. g., by
means of ammoniacal alcohol.

The bark of the Cascarilla magnifolia, mentioned on pages 10 and
48, agrees very nearly, in regard to its structure,* with the Cinchona
cuprea. The cork cells of the former, however, are thin-walled,
as in the Cinchonas, and its bast-fibres do not form such long,
straight rows as in Cinchona cuprea, where they may be followed
uninterruptedly from the youngest portion of the bast even into
the outer bark.

Hesse has shown? that in this Cinchona cuprea, which I saw for
the first time in his collection, the same alkaloids are present as in
the Cinchona barks. Since the Cinchona cuprea, independent of
the other bases, affords uniformly from 1 to 2 per cent. of quinine,
it is the more willingly worked by the manufacturers, as in conse-
quence of the absence of cinchonidine’ the preparation of pure
sulphate of quinine from this bark is rendered much easier.

The tannic acid of the Cinchona cuprea, according to Hesse, is
not the same which exists in the Cinchona barks, although the
former likewise produces a dark green precipitate with ferric salts.
Hlasiwetz, in 1867, ascertained that the tannic acid of coffee, by
boiling with caustic alkali, may be’ split into sugar and caffeeic acid,
C,H,O,, one of the hydro-cinnamic acids C,H,<Gén-co-on- Ker-
ner, in 1882, treated an alcoholic extract of Cuprea bark in the
same manner, supersaturated the liquid with sulphuric acid, and
agitated it with ether, which then furnished crystals of caffeeic acid.
The yield amounted to about ¥% per cent. of the bark employed.

1 This is well figured in Berg's Chinarinden der pharmakognostichen Sammlung 2
Berlin, 1865, Plate X, Fig. 27. In the innermost portion of the bast there are many
more fibres than here—compare our Plate VIII. 5

2 Berichte der Deutschen Chemischen Gesellschaft, 1871, p. 818. cee

8 According to Hesse, Berichte der Deutsch Chem. Ges. 1883, pp. 59, 60, homo- —
cinchonidine, dicinchonine, quinamine and conquinamine have also never been met
with in cuprea bark. (F.B.P.) — me bras

54 : CINCHONA BARKS.

The extracts of other Cinchona barks afforded by the same treat-
ment no caffeeic acid. This investigation was instituted in conse-
quence of crystals of caffeeate of quinine having been found in the
mother liquids obtained from Cinchona cuprea in the quinine manu-
factory at Milan. .

All the Cinchona cuprea which I have obtained from London and
New York, as also from Jobst’s manufactory, near Stuttgart, and,
furthermore, e. g., that which J have inspected in large amounts in
Zimmer's manufactory at Frankfort, always represented one and
the same product. Triana states that the districts southeast of
Bogota, mentioned on page 20, also furnish the same bark; the
latter he derives with precision from the there described Remzazia pe-
dunculata, to which thus the bark from Bucaramanga may prob-
ably also belong.’

Among the: Cinchona cuprea which reached France, small
amounts of a bark have, however, been found by Von Arnaud,’
which, according to Planchon, is essentially distinct from my Cin-
chona cuprea. As Arnaud has discovered in that a new alkaloid,
cinchonamine, the respective variety may here be designated as
Cinchonamine bark. It is, as stated by Planchon,* mostly deprived of
the warty cork, and displays upon a transverse section about 10 rows
of small, isodiametrical or polygonal cells, which, toward the interior,
gradually become extended in a tangential direction, and thereby
impart to the transverse section a peculiar delineation. In the
bast there are very numerous, densely crowded fibres with consider-
able cavities, in radial rows, which are separated by medullary rays
of from 4 to 5 cells in width. On a longitudinal section the fibres
appear slightly elongated, and short sclerenchyma cells and lacti-
ciferous ducts are wanting, while my Cinchona cuprea is particularly
characterized by the abundant development of groups of scleren-
chyma.’ The bast of Cinchona cuprea displays, as may be observed
in Plate VIII, two distinct strata; according to Planchon’s intima-
tion this is not the case in the bast of the Cinchonamine bark,
although, indeed, here also the fibres in the outermost bast layers
occur somewhat more numerously than in the inner.

1 Fourn. de Pharm., V (1882), p. 567; also Pharm. Journ. XII (1882), p. 861.
2 Repertoire de Pharm. 1881, p. 507.

8 The name cévchonamine was already bestowed by A. C. Oudemans, in 1879, to
another alkaloid, which has not been met with again since it was discovered.

* Journ. de Pharm. V (1882), p. 354, ‘‘ Quinquina A cinchonamine;” and VI, p. 89,

“Note sur les Ecorces de Remijia.

® | unfortunately did not succeed in obtaining the Cinchonamine bark. It is presum- .

ably the same bark which, according to the Pharm. Yourn. XI, p. 895, als od
once in 1881, in London. . F ~— 895, also appear

COMMERCIAL STATISTICS. 55

Of the tree, which in the valley of the Magdalena (probably
more correctly in the central district, between the Cauca and
Magdalena?) furnishes the Cinchonamine bark, Triana™ procured
the required organs, in order to be able to determine that it is the
Remiia Purdieana, mentioned on p. 20. By a comparison of this
material with the Cuprea barks occurring in commerce, Plan-
chon has definitely established the derivation here given of my
Cinchona cuprea, as well as that of the Cinchonamine bark.

SECTION XII.
COMMERCIAL STATISTICS.

A conception of the large dimensions of the commerce in Cin-
chona barks is given by the following figures :*

According to an estimate in the London Pharmaceutical Four-
nal of September 18, 1880, there are annually more than 6 million
kilograms of Cinchona bark (considered in the dry state) peeled
and brought into commerce. The following statements indicate that
this figure is well founded. If one may accept that the average
value of one kilogram of Cinchona bark is from 4 to 5 marks,‘ the
annual cinchona harvest would be worth, at the present time, nearly
30 million marks (nearly 7% million dollars).

Among all the drugs, only Opium attains to still larger sums; by
far the smallest part of which, however, serves for medicinal pur-
poses. Indeed, in the case of the Cinchona barks also, only a
small and not easily estimated portion finds direct application in
pharmacy. : :

In the year 1880 there were exported from the northern part of
South America, in Ciudad Bolivar, 29,650 kilograms (in 1881 only
6,650), from Puerto Cabello 24,107 kilograms, and in Barranquilla
(Sabanilla) 3,797,861 kilograms of Cinchona; in 1881, the latter
figure, consisting chiefly of Cinchona cuprea, was increased to
6,838,920 kilograms. ee

Ecuador, presumably inclusive of the neighboring districts of
Peru, furnished in 1880, via Guayaquil, 1,516,102 kilograms of
bark; in 1881 only about half so much.

1 Pharm. Fourn. Xi, p. 861; Fourn. de Pharm. V, p. 567.

2 For a part of these figures I am indebted to the obliging communications of Dr. G.
Kerner (emis quinine mamebactory); of Frankfort, Mr. David Howard, of Stratford,
and Mr. Gehe, of Dresden, while the remainder were obtained from official reports com-
pared by myself. Be eo

? 1 kilogram = 2 lbs, 3% ozs, nearly, avoirdupois,

4 1 mark = about 23 cents, U. S. currency.

56 CINCHONA BARKS.

In 1877 there were exported from Bolivia 56,620 kilograms by
water to Para, 254,009 kilograms to Arica, and 374,309 kilograms
to Molendo (south of Islay and Arequipa). :

The export from Ceylon amounted, in 1870, to 86,000, in 1880,
to 186,000, in 1881, to 600,000 kilograms, and for 1882 it is estimat-
ed at about 1 million kilograms.’ It may be presumed that in 1885
the export will amount to at least 4 million kilograms.

The plantations of the Dutch Government, in Java, had furnished,
in 1879, but 35,000 kilograms, in 1880 more than 55,000 kilograms,
in 1881 already 81,043 kilograms, and at the principal auction at
Amsterdam, May 23, 1882, 81,000 kilograms were offered for sale.
There are, moreover, also noteworthy plantations of private owners
upon the island, which, in 1881, had already furnished 522 bales
and 64 chests of Cinchona bark to the Amsterdam market.

In May, 1880, the first supplies from Jamaica came to London,
which, in March, 1882, had already attained to more than 15,000
kilograms.

In 1878 the import of France amounted to somewhat more than
1,600,000 kilograms of Cinchona bark, ata value of 11,201,988
francs, and in 1881 nearly as much. The United States received,
between 1874 and 1877, an annual average of 3,853,662 pounds,
and in 1881 nearly the same amount.

London is the princial point for the commerce in Cinchona barks.
The import of this place, which amounted to 1,140,000 kilograms
in the year 1876, has since regularly increased, to a particular
extent in the year 1881, and exceeded in’ the past year 6 million
kilograms. If there be added thereto that which is imported into
Paris, New York, Hamburg and Amsterdam, the total harvest of
Cinchona bark for 1876 may be estimated at 3% million, for 1881,
however, at 9 million kilograms. Hamburg, with an annual im-
portation of about 30,000 to 80,000 kilograms of Cinchona bark,
comes scarcely more into consideration than Amsterdam, where
i brought the barks which are grown almost exclusively in

ava.

Since 1876 the greatest increase is to be seen inthe imports
from India and Columbia (New Granada). From the latter country
4,797,000 kilograms were received in London in 1881, which,
indeed, includes the Cinchona cuprea, the occurrence of which,
however, is probably but transitory. On April 1, 1881, there were
stored in London 26,805 coli of Cinchona bark, thus at least

1 The export from Ceylon has already attained to more than 1% million kilo: ms ;
that of Java, in 1881, 165,000 kiloprasak: : : eT

COMMERCIAL STATISTICS. 57

1,340,000 kilograms." At the beginning of July, 1882, the supply
there amounted to 3% million, and in Paris to about % million
kilograms.

If one attempt to estimate the amount of sulphate of quinine?
(including the other salts of quinine and the remaining Cinchona
bases) which is annually manufactured in recent years, there results,
with some degree of probability, the figure of 120,000 kilograms,
which presupposes nearly 86,400 kilograms of alkaloid. If it then
be assumed that the barks contain, on an average, but two per
cent. of alkaloids, the manufactories must annually work up about
4% million kilograms of Cinchona bark; at the present day,
however, it may be presumed to be considerable more.

The commercial reports are accustomed to calculate according
to collt (serons, bales), which contain from 50 to 55 kilograms of
bark,

If one will assume that for each of the nearly 5000 pharmacies?
of Germany there is a daily consumption of 100 grams of Cin-
chona bark, this figure, which is undoubtedly too highly estimated,
would correspond to an annual requirement of 182,500 kilograms.
in the year 1881, however, the import of Germany (after deduct-
ing 119,200 kilograms, which again went out of the country)
amounted to 2,048,600 kilograms; 1,876,100 kilograms of bark had
thus probably become worked up for alkaloid in the 6 quinine
manufactories of Germany, and may have furnished more than
50,000 kilograms of sulphate of quinine.

1 In December, 1881, a ring of speculators placed themselves in possession of the
largest part of Cinchona bark stored there, which was estimated at about 40,000 co//, or
over 2 million kilograms, and among which Cinchona cuprea was present to the largest
extent.

2 The present price of sulphate of quinine is nearly 300 marks per kilogram. One
may thus be permitted to assume that the amount of cinchona alkaloids and their salts
which are annually manufactured represent in the world’s market a sum of from 30 to
40 million marks (about 7% to 1o million dollars). An indication of the great fluctu-
ations in this department may moreover be given by the following extremes in the selling
price of sulphate of quinine from Zimmer’s manufactory at Frankfort-on-the-Main, in
the interval from 1875 to 1881. A kilogram of this salt was quoted:

at 195 marks in January, 1876; at 545 marks in May, 1877;
at 260 “a February, 1878; at 440 6s May, 1879;
at 240 ae November, 1881; at 430 a August, 1880.

3 According to the last statements contained in the Imperial Statistical Office (March,
1882), there existed in the year 1875, in the German Empire, 4531 pharmacies.

58 CINCHONA BARKS.

SECTION XIill.
CHEMICAL CONSTITUENTS OF THE CINCHONA BARKS.

An odor is not entirely foreign to the Cinchona barks ; Weddell’
found it, ¢. g., in the case of fresh Calisaya and amygdalifolia, to
resemble that of elder bark, although more feeble. Also in some
varieties of commercial barks, ¢. ¢., that of flava fibrosa (p. 44) and
of Loxa (p. 47), a slight aroma cannot be entirely ignored.
slight aromatic odor is already perceived when the powdered fresh
bark of the Indian C. succirubra is dried with milk of lime. Hesse’
also makes mention of an odorous principle in the Cinchona barks.

The barks of some of the Rubiaceze which are most closely re-
lated to the Cinchonas, have a decidedly agreeable odor, thus, e. 2.,
that of Ferdinandusa chlorantha Pohl (Gomphosia chlorantha
Weddell).

In regard to the taste, there occur, in part, significant distinctions.
Younger barks have a predominating, but not disagreeably astrin-
gent taste (saveur styptigue of Delondre and Bouchardat), more
rarely, as, e. g., those of Huanuco and Loxa, at the same time
astringent acidulous, although to a less extent. In trunk barks the
astringent tang becomes more and more lost, and the pure bitter
taste appears strong and prominent.

' In the case of the Calisaya, the pure bitterness appears even with
young barks, while the more diminutive C. scrobiculata always
possesses the astringent tang, which occasionally predominates.

In the C. pubescens, which is likewise poor in alkaloid, Weddell?
perceived, even in fresh trunk barks, only a somewhat bitter and
at the same time nauseating taste.

A disagreeable and at the same time a somewhat sharp tang is
observed in the so-called Cinchona (China) Faén vel Parad fusca,
in which the Cinchona bases are wanting; its botanical origin is
not known.*

Among the universally distributed principles of the vegetable
kingdom, which also occur in Cinchona barks, prominence has
already been given to the directly observable starch and calcium
oxalate. Since the latter is in crystalline granules and only

1 Hist. Nat. des Quinguinas, pp. 33, 45-
2 Berichte der Deutschen Chemischen Gesellschaft, 1877, p. 2162.
8 Hist. nat. p. 56, Note 2.

* Compare Fliickiger’s Pharmakognosic, first edition, 1867, pp. : ye , where,
however, the structure of true Cinchona barks has erroneously con poten to this

CHEMICAI, CONSTITUENTS OF THE CINCHONA BARKS. 59

deposited in isolated cells, it comes but little into consideration.
The total ash of bark dried at 100° C. (212° F.) attains, according
to Reichardt,’ to a maximum of about 3 per cent. (in Cinchona
rubra); the amount of lime to about 1 per cent. Howard? obtained
from the inner portion of the bast of C. succirubrao.g1 per cent.
of calcium carbonate, corresponding to 0.5 per cent. of lime. On
the other hand Reichel estimated the amount of oxalic acid (in
Huanuco bark, p. 46) to be in maximum 0.29 per cent., and
Reichardt (in Cinchona rubra) as 0.33 per cent., wherefrom may be
deduced that the amount of never-failing oxalate cannot readily
exceed 1 per cent., in that, presumably, a portion of the calcium is
contained in the form of other compounds.

The ash remaining by the combustion of the Cinchona barks,
fluctuating from 34 to 3 per cent., consists for the most part of the
carbonates of calcium and potassium, which, together, e. g., in the
flava fibrosa, according to Reichardt, represent + of the entire
amount of ash. Very much smaller is the quantity of magnesium
carbonate, which, e. g., in flat Calisaya, amounts to but 3; of the ash.
Cinchona cuprea afforded me 1.65 percent. of ash. Conclusions as
to the distribution of the constituents of the ash in the different
forms of tissue of the bark appear premature. I found carefully
isolated bast fibres to be poor therein.

The presence of ammonium salt may readily be demonstrated in
the extracts of Cinchona barks, although its amount, on an average,
is probably but very small. Carles, in 1873, obtained only fractions
of a per mille. of ammonia.

Substances which may be designated as rveszz are also contained
in the barks in but very insignificant amounts. Delondre and Henry
found such in the red juice exuding from the trunks of Cinchonas
as the result of incisions.

If Cinchona barks be extracted with boiling alcohol, a principle
is separated in the cold which has been regarded as wax, and which,
occasionally colored with chlorophyll, may also be obtained when
specimens of bark are analyzed simply for the purpose of estimating
the alkaloids. Kerner (1859, 1862) has designated this principle as
cinchocerotin.2 When prepared frem flat Calisaya it forms, after
purification, handsome, purely white, neutral, crystalline lamine
which first melt at about 150° C. (302° F.) |

1 Title under section XVIII.

* Nueva Quinologia, Microsc. observat., fol. 6. :

* Cinchocerotin is not a wax; for athorough investigation of itsee Helms’ paper in
the Archiv der Pharmacie, April, 1883, and abstracted in the Amer. Fourn. Pharm.,
July, 1883. oe : ie

60 CINCHONA BARKS.

The presence of gum, as also of sugar, has not been more
accurately proved in the Cinchona barks. __

The phlobaphen which, in 1844, was precipitated by Stahelin and
Hofstetter from an alcoholic tincture of the yellow Cinchona by
means of sulphuric acid, as also the /ignomm, prepared in 1856 by
Reichel, are quite as insufficiently investigated as the corresponding
substances occurring in oak bark.* Reichel’s lignoin may be
obtained when Cinchona, which has been exhausted by ether,
alcohol and water, is extracted with caustic lye, and is then pre-
cipitated, on the addition of an acid, as a dark brown substance,
which, in its dry state, may amount to from 2 to 1g per cent. of the
bark.

The Cinchona barks contain tannin, which affords with ferric
salts a bright green, or, when other coloring principles of the
barks co-operate, a darker brownish-green precipitate. This czzcho-
tannic acid also produces a precipitate in a solution of gelatin.
Reichardt found in Cinchona (China) flava fibrosa 1 per cent., in

flat Calisaya 3%, and in quill Calisaya, 2 per cent. of tannic acid ;
Reichel, ‘in flava fibrosa (the Tunita bark mentioned on page 18),
3.8 per cent. When separated from the lead salt, the cincho-tannic
acid represents, according to Schwarz (1851), a bright yellowish,very
hygroscopic mass, of an acidulous, and at the same time astringent,
but not bitter, taste. Upon heating the cincho-tannic acid at but
100° C, (212° F.), or by the evaporation of its aqueous solution,
especially after the addition of acids or alkalies, red products are
formed—in the latter case with absorption of oxygen. By precipi-
tating the red-brown ammoniacal extract of Cinchona with an acid,
the cznchona-red is obtained, which, when dried, is a dark red or
brownish-red, odorless and tasteless mass, insoluble in ether, water,
and dilute acids, but soluble in alcohol. The ammoniacal solution
of cinchona-red affords, with alum, a red lake. With a fraudulent
purpose, the attempt has already been made to impart to yellow
Cinchona barks the appearance of the more expensive red varie-
ties by moistening them with ammonia. The aqueous extract of a
bark which has been treated in this way is remarkably colored, and
affords, with Nessler’s reagent? a reddish-brown, not a white pre-
cipitate; chloride of platinum also produces an abundant precipi-
tate, while the Cinchona barks, as previously intimated, p. 59, can
furnish but very little ammonio-platinic chloride. :

1 Flickiger, Pharmakognosiz, 1882, p.475.

2 Fliickiger, Pharm. Chemie.,1878, p. 38; Kubel and Tiemann, An/ettung zur Unter-
suchung von Wasser, 1874, p. 142; Hoffman and Power's Examination of Medicinal
Chemicals, p. 40. oe a eee

3 Thomas et Guignard, Répertoire de Pharmacie, 1882, p. 337-

CHEMICAL CONSTITUENTS OF THE CINCHONA BARKS. 61

The amount of water contained in air-dried Cinchona barks
seals usually to from g to 11 per cent. (Compare also page
34:
The oldest observation which relates to the peculiar constituents
of Cinchona barks, or at least to those which are characteristic of
them, reverts to the year 1745, when Claude Toussaint Marot de
Lagaraye, of Paris, perceived the deposit of a salt from an extract
of Cinchona.t. S. F. Hermbstadt, of Berlin, in 1785, recognized
therein the calcium compound of an acid, the peculiarity of which
was established in 1790 by Friedr. Christian Hofmann, an apothe-
cary of Leer, in Hanover, who named it chzmasdéure (kinic acid).

Vauquelin, in 1806, determined more precisely the properties,
and Liebig the composition, of kinic acid. It occurs in all true
Cinchona barks, in amounts of as much as g per cent., and upon it
depends the acid reaction of their aqueous extracts; it is, however,
without any considerable physiological action. Hlasiwetz, in 1851, —
found kinic acid also in the Cinchona nova, mentioned on page 49.
Since, according to Hesse, it is absent in the Cinchona cuprea, it
would be desirable to know its distribution in the group of the
Cinchonez, the more so as it belongs to those plant acids which
are of quite common occurrence. Kinic acid forms large, hard,
monoclinic crystals, which are soluble in somewhat more than twice
their weight of water. The solution is odorless, of a purely acid
taste, not bitter, and deviates the plane of polarization to the left.
According to its constitution, C,H,(OH), CO-OH, and that of its
derivatives, the acid belongs to the class of aromatic compounds;
by the action of hydriodic acid it may be reduced to benzoic acid
and protocatechuic acid, and by energetic oxidation may be con-
verted into quinone (or kinone). In closest relation to kinic acid
stands the so-called acorn-sugar, or quercite, C,H,(OH),.

In the barks of the Cinchonas and the most closely related Ru-
biaceze, there is found an uncrystallizable bitter principle, c¢novzn’

1 Chymie hydraulique, sig extraire les sels essentiels des végétaux, animaux et miné-

raux avec l'eau pure, par M. L. C. D. L.G._ (Monsieur le comte de la Garaye), Paris,
1749, 114. The Count occupied himself with chemistry for philanthropic purposes.

2 According to recent researches of Liebermann and Giesel, Berichte der Deutsch.
Chem. Gesellschaft, 1883, pp. 926-941, the chinovin obtained from cinchona cuprea Is
not identical with dacobtaln from the true cinchonas, but only isomeric therewith ;
the former they designate as # chinovin, and the latter as a chinovin. Both substances,
in a pure state, form a white, very loose, crystalline powder, but differ in their behavior
to solvents and in some chemical reactions. Thus the §, in distinction from the @ chi-
novin, is insoluble in absolute ether and in acetic ether, while the # compound is much
more freely soluble in oon one lute wscurcungl™ ones by Pg eer have the —
elemen composition, which is provisionally r ed by the authors as corresponding _
to the poh CH, 2031, while aa of chinovic acid is regarded as C,;,H,,O0,. The

62 CINCHONA BARKS.

(quinovin or kinovin). It was discovered in 1821 by Pelletier and
Caventou, in Cinchona nova surinamensis, and named by them
“acide quinovique’”’; it was afterward designated by others as chzno-
va-bitter or cinchona-bitter, and in 1859 was recognized by Hlasi-
wetz as a glucoside. Chinovin is best extracted from fresh
Indian barks by means of a dilute alkali, and is precipitated there-
from, according to De Vrij, by hydrochloric acid. In order to
purify it, the chinovin is dissolved in milk of lime and again pre-
cipitated. After having been subjected to this treatment several
times, it is finally dissolved in chloroform. Chinovin is scarcely
soluble in water, but is soluble in acetone, ether and alcohol;
although neutral, it forms compounds with the alkalies, which are
mostly soluble in water, and possess a very bitter taste. It is
probable that a portion of the alkaloids in Cinchona barks is in
combination with chinovin. According to Hlasiwetz, chinovin,
C,.H,,O,, in alcoholic solution, is split, by the action of hydrochloric
acid, into chimovie (quinovic or kinovic) acid C,,H,,O, and a smeary
variety of sugar (afterward recognized as mannitan),* C;H,,O
whereby a molecule of water is absorbed.

CZN,0, + HO == 0,H,0, + CjH;,,0;

patie, cvsnet Sy ie aE. pall

Chinovin. Chinovie Acid. Mannitan.

If an alcoholic solution of chinovin, diluted with a little water, is
brought in contact with sodium amalgam, there is obtained, upon
concentration, chinovate of sodium, as Rochleder (1867) has
shown.

Chinovin participates in the medicinal activity of Cinchona
barks.* The plane of polarization is deviated by its solutions, as
well as by those of chinovic acid, to the right. The latter forms
rhombic laminz, and is of a feebly acid nature; it dissolves only
in boiling alcohol somewhat abundantly, but neither in chloroform
nor in water. Chinovin, associated with chinovic acid, is not con-
fined in the Cinchonas to the bark, but is distributed through all
their parts. De Vrij, in 1860, found in dried leaves of Cinchonas
cultivated in India as much as 2 per cent.;in the trunk bark as
much as 1.4 per cent., and in the root bark 1 per cent. of chinovin;

decomposition of chinovin is thus considered to take place according to the following
equation Cian

Kid

C,sH,20),; = C32H 4,06 + C.H,,0, + H,0.
te ————— ay ;
; Chinovin Chinovic acid Chinovin sugar.
_ 1 Liebermann and Giesel, /oc. cit., p. 935, place the identity of this sugar with mannitan
in question, but find the sugar obtained by the decomposition of both varieties of chino-
vin to be identical. (F. B. P.) ;

* Kerner, in the Géschen Deutsche Klinik, 1868, No. 9.

CHEMICAL CONSTITUENTS OF THE CINCHONA BARKS. 63

the maximum, however, of 2% per cent. in the wood of the root.
Reichardt has obtained from Huanuco bark 134 per cent., Reichel
quite as much from Cinchona flava fibrosa (p. 44), and Howard’
4.28 per cent.

Whether Cinchona barks exist in which this bitter principle is
wanting, still requires proof.

For the detection of the active principles of the Cinchona barks,
experiments were already instituted in the preceding century,
although Gomes was the first who, in 1810, and more completely
in October, 1811, succeeded to any extent in the preparation of
the alkaloids from the Cinchona barks. He dissolved an alcoholic
extract of Cinchona in water, and precipitated by potassa a body
which he re-crystallized from alcohol, and named cinchonine. That
this preparation was of a basic nature, was first observed by Houtou-
Labillardiére in the laboratory of Thénard, at Paris, and com-
municated to Pelletier and Caventou.s To these chemists, who
were guided by Sertiirner’s brilliant discovery of morphine,‘ we are
indebted for a more precise acquaintance with Gomes’ cinchonine,
and the proof (1820) that two basic principles, quinine and cincho-
nine, are contained therein, to which the therapeutic effects of
Cinchona belong. It is the former upon which almost exclusively
the value of Cinchona bark depends.

The following bases occur in noteworthy amounts in Cinchona
barks :—

Quinine, ‘ : : ‘ 5 ‘ a ‘ : : C,oH,,N,0,
Quinidine,® discovered by Henry and Delondre, in 1833, . ; : bene:
Cinchonine, —. ‘ ; ‘ wii s “ = ‘ ‘ Dees BS Pe 8
Cinchonidine, discovered by Winckler, in 1847, . A - pair wl

1 Examination of Pavon's Collection of Peruvian Barks contained in the British Mu-
seum, London, 1853, 8vo, pp. 47 (From the Pharm. Fourn., June, 1852).

2 Ensaio sobre o chinchonino, Lisboa, 1810. A translation in the Medical and
Surgical Fournal, Edinburgh, 1811, p. 420. More extended in Memor. da acad. real
das Sciencias de Lisboa, U1 (1812), pp. 202 to 217: Ensaio sobre o cinchonino, e sobre
sua influencia na virtude da quina e d’outras cascas. Antonio Bernardino Gomez was
a Portuguese physician, who spent the last years of the eighteenth century in Brazil,
then lived in Lisbon, and died there in 1823. In 1801 there appeared there his ‘‘ Memoria
sobre a Ipecacuanha fusca do Brazil ou Cipé das nossas boticas;” in 1801 and 1809, in
Rio Janeiro, two essays on the cultivation of cinnamon, and finally the above notice
relating to cinchonine. Compare Colmeiro, La botanica y los botanicos de la peninsula
hispano-lusitana. Madrid, 1858, pp. 58, 199.

3 Annales de Chimie et de Phys., XV (1820), p. 292. Houtou-Labillardiére died, in
1867, at Alencon. For the discovery of the cinchona bases, Pelletier and Caventou
received, in 1827, from the Institut de France, the Montyon prize of 10,000 francs. In
the year 1826 there had already been prepared at Paris 90,000 ounces (more than 2700
kilograms) of sulphate of quinine. Berzelius, Fahresbericht der Chemie., VIII (1829),
page 246. aoe ;

4 Flickiger, Pharmakognosie, second edition, 1881, p. 176. __ ee ey

5 Betachinin, Van Heijningen, 1849, and Koch, 1861; cinchotin, Hiasiwetz, 1850; de-
tachinidin, Kerner, 1862; conchinin, Hesse, 1865. See Liebig's Annalen, 192 (1878),
p. 192. Archiv. der Pharm., 216 (1880), p. 259, etc.

64 CINCHONA BARKS.

The Cinchona barks contain, furthermore, in smaller amounts:

Homocinchonidine, discovered by Hesse, in 1877 a eaihs Dake Ci 4N,O
Cinchonamine, obtained in 1881 by Arnaud, from Remijia Purdieana (p. 54)C,,H,,4N,0
Homoquinine, found in 1882 by D. Howard and other English investigators,

in Cinchona cuprea a . : Sa : Cy ohiaatsOs
Quinamine, discovered by Hesse, in 1872 i A " ‘ i ot MG yobs ZO
Conquinamine, “ “ WOGRTY a at eh ee 1 ak wand e mn
Cinchamidine, eee * 1881 : : : ete Sys Fey

Quinine and cinchonine stand at the head of two groups of
alkaloids, which, indeed, individually, show quite broad distinctions,
but present, however, with regard to their physiological action,”
some agreement. From these distinctive cinchona alkaloids the
following bases are very considerably separated in every respect :
Aricine, discovered by Pelletier and Coriol, in 1829,? and analyzed by

Hesse, in 1876 . . . . . . . . Saye. AP ae A
Cusconine, discovered by Hesse,* in 1877 a : ‘ : ‘ * Seagetees,
Cusconidine, fe ties he ERTe . F
Cuscamine, * fe elt ABS : : ; ‘ ; wie by!
Cuscamidine, “ “ “ “ 1880 : pitas saan
Paytine*, eee t Meret Bayo _ ‘ ‘i ‘ ‘ ‘ C,,H,,N,0
Paricine, in the bark from Para, mentioned on pages 58 and 68, discovered

by Winckler, in 1845 = ° , : : ‘ “ : ‘ Bisset Soc

With the exception of paricine, cusconidine, and cuscamidine,
the above named alkaloids are crystallizable. Besides the former,
there occur however, other amorphous bases’ in Cinchona barks,
the knowledge of which is still but slightly satisfactory, They are
perhaps first formed, in part, from the crystallizable alkaloids, in
the process of manufacture. The chznotdin of the manufactories
consists, for the most part, of amorphous bases. ;

Hesse® isolated from the mother liquids of Cinchona barks,
obtained from the manufactories, the slightly odorous cincholine, a
base volatilizable with aqueous vapor, but which, however, may

? It is only in the case of quinine that this has been satisfactorily determined from a
medical standpoint.

? In a bark of unknown botanical origin, which was exported a few times from Arica
(see p. 32), and which may possibly belong to a Cinchona.

* From barks which have not been botanically determined; the name relates to
Cusco, in southern Peru. =

Hesse, Berichte der Deutsch. Chem. Ges., 1883, pp. 58-63, announces the presence of
two new alkaloids in a variety of “‘cuprea” bark, viz: concusconine and concusconidine,
cg eh, the composition C,,H,,N,0,; and the list appears not yet completed. (F.

4 In a so-called white Cinchona bark, which was once exported from Payta, the most
northerly port of Peru, but is not to be met with in commerce. Com ta

i iy pag te pare, regardi the
same, Fliickiger, Jahresbericht der Pharm., 1872, p. 132; also section 18, No. 35, of this
wont 5 se tae 5

* Every Cinchona bark contains amorphous alkaloids. Bernelot Moens, in 1881,

states that their quantity varied from 0.13 to 1.4 cent., as ascertained from 8
analyses perf by him. ra hark eos g

® Berichte der Deutschen Chemischen Gesellschaft, 1882, p. 858. pe

CHEMICAL CONSTITUENTS OF THE CINCHONA BARKS. 65

possibly only originate from the hydrocarbons employed in the
process of manufacture. (See section 15.)

From the first named alkaloids, on page 63, there are formed, by
the action of potassium permanganate:' cénzchotine, hydroguinidine,
(hydroconchinine), Aydrocinchonine and hydrocinchonidine, which,
according to Forst and Béhringer (1882), are said to originally
exist in Cinchona barks. :

Only the two first mentioned pair of alkaloids (p. 63) are em-
ployed medicinally; they have a very bitter taste.

Quinine may be obtained in a crystalline form with 3H,O; it is
soluble in about 20 parts of ether, more abundantly in alcohol and
chloroform. These solutions deviate the plane of polarization to
the left. Quinine is soluble at 15° C (59° F.), in 1600 parts of
water. This solution, as also the aqueous solutions of quinine
salts, when treated with chlorine-water or bromine vapor and am-
monia, in the manner described in my Pharmaceutische Chemie,’
1878, p. 410, affords a green precipitate of so-called thalleioguin, or
a beautifully green, clear solution. Quinine salts of the oxygen
acids show, under the circumstances described in the previously
mentioned work, page 409, a blue fluorescence. Quinine itself is
but little used; in medicine the sulphate (C,,H,,N,O,),H,SO,+7
H,O3 is particularly employed, as also the hydrochlorate of qui-
nine.

Quinidine (conquinine or conchinin) readily yields crystals having
the composition (C,,H,,N,O,), +5H,O, but which readily effloresce.
It is less abundantly soluble in ether than quinine, and its solutions
deviate the plane of polarization to the right. In regard to fluor-
escence and the thalleioquin reaction, quinidine shows the same
behavior as quinine. :

Cinchonine is not capable of combining with water of crystalli-
zation ; it dissolves first in 400 parts of ether, and, even by alcohol,
is not abundantly taken up. | :

Cinchonidine crystallizes likewise only in an anhydrous condition,
is more abundantly soluble than cinchonine, and its optical behavior
is the reverse of the latter. ae :

Some noteworthy properties of this group of cinchona alkaloids,
in a restricted sense, to which may &till be added homoquinine and

1 Compare Kerner, FYahresbericht der Pharm. 1869, p. 313; also Strecker’s Fahres-
bericht der Chemie., 1869, p. 718. i :

? See also Pharmacographia, second edition (1879), p. 360. ey .

3 It is not definitely established whether this salt contains 7 or 8 molecules of water of
crystallization, or perhaps an intermediate amount.

“ ai

66 CINCHONA BARKS.

the, indeed, very different quinamine, may be summarized as
' follows :—
a. Hydrated crystals are formed by Quinine, Quinidine.

Cinchonine, Cinchonidine.

Not containing water of crystallization | Quinamine, Homoquinine.

b. Abundantly soluble inether . . | ae oe
Slightly " Ven ; : Cinchonidine, Cinchonamine.
Very sparingly “ we poe Cinchonine.
c. Levogyrate solutions afforded by : Quinine, Cinchonidine.
Pextrouventl ie ate Quinidine, Cinchonine,
8Y Quinamine.

Quinine, Quinidine,

d. Thalleioquin is afforded by 2 ae Homoquinine.

“ iamde. ot 1 Cinchonine, Cinchonidine,
z . Quinamine.
e. Fluorescence is displayed in the acid
solutions of salts of . ‘ a Quinine, Quinidine, Homoquinine.
No fluorescence is displayed by Cinchonine, Cinchonidine, Quinamine.

The amount of alkaloids' which the Cinchona barks contain is
subject to considerable variation. Karsten pursued this investi-
gation, e. g., in the Cinchona corymbosa discovered by him, the
trunks of which, at elevations of 3500 meters (11,375 feet), on
the South-Colombian volcanoes, Cumbal and Chiles, furnished no
quinine. Barks grown at other parts of this district afforded 34 per
cent. of quinine, and those from the central elevated regions,
which this handsome species’ inhabits, 114 to 3%4 per cent. of sul- °
phate of quinine. Cinchona lancifolia, taken in the neighborhood
of Bogota from one and the same mountain ridge, contained in
the bark of the branches no quinine, or only insignificant traces of
the same, while trunk bark from another place gave 2, and even
4%, per cent. of sulphate of quinine.

Variations not less in extent have been proved by De Vrij? to
occur with Cinchonas grown in Java. Calisaya trunk barks, 7
years old, gave 0.64 per cent., and those of 6% years, from another
plantation, 5 per cent. of total alkaloids. In 1873, he found in the
bark of Cinchona officinalis, from Ootacamund, 1 Y to g.1 per cent.
of quinine.

In the bark of Cinchona pubescens Vahl, which, indeed, is un-
salable, Hesse, in 1871, found no alkaloid at all.

1 The analytical statements frequently tefer to sulphate, and not to the amount of the
bases themselves, directly separated from the bark. 100 parts of sulphate of quinine =
64 of quinine; 100 of quinine = 135 of sulphate. The Dutch analyses state the per-

centage of alkaloid of barks dried at 100° C. (212° F.); these values, therefore, on ac-

count of the average amount of water, 13.5 per cent. (see p. 34), must be multiplied by
0.865, in order to correspond to an ‘ie iiteed vibe: gh te raed

* Figure: plate X of the Flora mentioned in section 18, No. 12: also copied there-
from (uncolored) in Markham’s publication (section 18, No. 21 of this work),

* Pharm. Fourn., V1 (1864), p. 16.

CHEMICAL CONSTITUENTS OF THE CINCHONA BARKS. 67

From the few, but striking, analytical results which are here
summarized, it is evident that external characteristics, including
histological relations, scarcely afford a criterion for the chemical
valuation.of Cinchona barks. If we must abandon the attempt of
determining for one and the same Cinchona a constant average
percentage, this applies in a very much higher degree to the com-
mercial varieties.

Between the complete absence of bases, and the maximum of
more than 13 per cent. of quinine," which has been observed up to
the present time, numerous gradations occur regarding quality and
quantity.

The barks of the roots appear regularly to be richer in alkaloids
than those of the trunks. De Vrij, in 1869, obtained from the
root bark of C. succirubra, grown in Ootacamund, 12 per cent. of
alkaloid.

Of the bark of Calsaya Ledgeriana, grown in Java, Bernelot
Moens, in 1879, examined 80 specimens. They afforded a mini-
mum of 1.09 per cent., and a maximum of 12.50 per cent. of
alkaloids, although only in 13 cases less than 5 per cent. The
quinine varied between 0.8 and 11.6 per cent. The same bark
furnished in following years, according to the estimations of the
above-named chemist, in 100 parts of artificially (page 34) dried
bark :—

1880 1881
Total alkaloids, in minimum, 4. , 3
fi " * maximum, 9- 9-
Quinine, in minimum, 2.3 1.2
« -“ maximum, 8. 8.1

In the Indian C. succirubra, whose total alkaloid readily amounts
to from 6 to Ir per cent., as was, moreover, already known to be
the case with the original Red Cinchona of South America, the
amount of quinine is small. The Indian bark often affords
but 1 per cent., more rarely about 4 per cent. of quinine, and very
commonly from 3 to 4 per cent. of cinchonidine. In the year 1881
the amount of total alkaloid from the bark of C. succirubra har-
vested in Java varied between 3.2 and 9.8 per cent., that of quinine
from 0.4 to 2.5 per cent., and of cinchonidine between 1.3 and 5.2
per cent. 3

The above analyses of Bernelot Moens refer to average spect-
mens from separate packages, the weight of which was from 200
kilograms, and even less, to some thousands of kilograms.

The wood of the roots and of the trunks of Cinchona, the latter

1 Blue Book, 1870, p. 282. Bernelot Moens, in 1882, obtained as much as 13.61 per
cent. of alkaloids from C. Ledgeriana.

68 - CINCHONA BARKS.

of which, according to Van Gorkom, is adapted for cabinet-makers’
work, contains, besides chinovin (see p. 61), occasionally about 1%
per cent. of alkaloids, as stated by Bernelot Moens, in the annual
report of the Javanese cultivation for 1880. :

The Zeaves of the Cinchonas have an acidulous, bitter taste, and,
after drying, an odor resembling tea. It is placed beyond doubt
that they contain an insignificant amount of alkaloids, the prepa-
ration of which, in a pure state, however, is attended with greater
difficulty than from the bark. Broughton, in 1870, obtained from
the leaves of the Indian C. succirubra, only fractions of a per mille
of alkaloid.'. According to the experience of English physicians
in India, which, indeed, is, as yet, not very extended, the leaves of
C. succirubra deserve consideration as a febrifuge.* Their taste is
due chiefly to chinovin, of which, e. g., in the last named species,
they contain as much as 2 per cent., and in general appear to con-
tain, on an average, more than the bark. The amount of chinovin
stands presumably in inverse proportion to the percentage of
alkaloids.

Still more bitter than the leaves are the flowers, the bitterness of
which, however, is not taken up by the aqueous infusion. Brough-
ton, in 1869, found them to contain chinovin, but no alkaloid.

The Cinchona fruits, which likewise have a bitter taste, contain
either no bases, or but an extremely small amount. O. Henry, in
1835, found none therein, as likewise DeVrij, in 1870; Broughton,
in 1867, met with doubtful traces of alkaloids in fresh capsules.

If quinine or cinchonine be heated with volatile organic or in-
organic acids, or with such substances as are capable of yielding
them, a beautiful red decomposition product is formed. Grahe,
assistant at the laboratory of the University of Kasan, has shown
(1858) that the same product may be very nicely obtained from
Cinchona barks. No other bases show this behavior, and barks
also which contain no cinchona bases do not afford this red product.
A red tar, indeed, appears also upon heating cinchona red (in so far
as the latter is not most carefully freed from the alkaloids?).

Grahe's test, in combination with the simplest microscopical
examination, therefore, affords an admirable means of furnishing
the proof whether a bark provided with Cinchona alkaloids is at
hand or not. By the entire absence, or extremely small percentage,
of Cinchona bases, this reaction is not obtained, even when using
a true Cinchona bark. Thus, e. g., with the Cinchona from Para,
and the bark designated by Winckler? as Calebeja, which possess

1! Blue Book, 1870, p. 238. 2 Blue Book, 1863, p. 264.
* Compare also Wigger’s Pharmakognosie, 1857, p. 355: ‘‘clove-brown Calebeja.”

QUANTITATIVE ESTIMATION OF THE ALKALOIDS. 69

the structure of true Cinchona barks, but contain, however, no
cinchona bases, but paricine. Cinchona nova surinamensis does
not give the red tar, which, however, is afforded by Cinchona
cuprea.

Hesse renders Grahe’s test more delicate by extracting with
alcohol the bark to be tested, drying the tincture with an appropriate
amount of powder of the same bark, and first heating the latter
product.

SECTION XIV. .
QUANTITATIVE ESTIMATION OF THE ALKALOIDS.

The estimation of the alkaloids may be quite satisfactorily ac-
complished by the following method :—

I. Twenty grams of a well selected, average specimen of the bark
is very finely powdered, moistened with ammonia water,’ and, after.
standing for an hour, mixed with 80 grams of hot water; it is then
allowed to cool, subsequently intimately mixed with milk of lime
(prepared by triturating 5 grams of dry caustic lime with 50 grams
of water,) and the mixture evaporated upon a water-bath until it
is uniformly converted into small, somewhat moist, crumb-like
particles. This is then transferred toa cylindrical glass tube (see
figure), which at A is 2.5 centimeters (1 inch) wide, and
from A to B 16 centimeters (6.4 inches) long. AtBa §
small brass sieve is inserted, upon which a disc of filtering gig
paper is secured by means of a bunch of loose cotton. ,/7/7
The powder having been quite compactly adjusted upon
the cotton, it is again covered at A, as in B, with a little | |
cotton; the latter having been previously employed for a gi
removing the last traces of the powdered bark from the fee
capsule. At Z, a tightly-fitting cork is inserted, which is
penetrated by the tube &, and connected with an invert-
ed, small, glass condenser. The lower end of the appa-
ratus, C, is tightly connected, by means of a cork, with
the flask X, containing about 100 cubic centimeters of
ether. The flask is then heated by means of a constantly ae
supplied water-bath; and in the same degree as the s fas
vapors of ether are expelled through D, they become
again condensed in the condenser—the liquid dropping ¢\!
through the tube R upon the powder at A, penetrating f/f
the entire column of powder 4 JZ, and flowing at tosab i jy
urated with alkaloid, into the flask A. To effect the com-

plete exhaustion of the bark by the ether, the operation
a "This effects a remarkable swelling and disintegration of the tissue.

70 CINCHONA BARKS.

of displacement should be continued uninterruptedly for nearly
a day, but when once in progress it requires but little atten-
tion. In order to determine whether the bark is completely
exhausted, a few drops of the ether, falling at C, are collected in a
test-tube, and mixed with about an equal volume of a solution of
potassio-mercuric iodide (0.332 gram potassium iodide, and 0.454
gram red mercuric iodide, in 100 cubic centimeters of water); no tur-
bidity should occur if the process of extraction has been sufficiently
long continued. When this is accomplished, 36 cubic centimeters of
one-tenth normal hydrochloric acid (3.65 grams HCl in 1 liter) are
added to the ether in the flask X, the ether distilled off, and sub-
sequently so much hydrochloric acid added as may be required to
impart to the liquid an acid reaction. After having cooled, the
liquid is filtered from the separated mixture of wax, chinovin and
chlorophyll, 40 cubic centimeters of one-tenth normal sodium
hydrate solution (4 grams NaOH in 1 liter), are added, and the
whole allowed to repose until the precipitate has subsided, and the
supernatant liquid has become perfectly clear. Sodium hydrate is
then gradually added to the liquid as long as a precipitate con-
tinues to be produced, for which purpose a solution of the spec.
grav. 1.3, is the most serviceable. The precipitated alkaloids are
afterwards collected on a filter, and gradually washed with a little
cold water, until a few drops of the washings, when allowed to flow
on the surface of a cold, saturated, neutral, aqueous solution of qui-
nine sulphate, cease to produce a turbidity. The drained precipitate
contained on the filter is then gently pressed between bibulous
paper, and dried by exposure to the air. It may afterwards readily
be removed from the paper without loss, and, after thoroughly
drying upon a watch-glass over sulphuric acid,* is finally dried at
100° C (212° F.), and weighed. The weight of the precipitate,
multiplied by 5, will give the total percentage of mixed alkaloids
in the bark.

If it is desired to accomplish the estimation of the alkaloids with
more simple apparatus, the ether may be substituted to advantage,
either wholly or in part, by higher boiling liquids; e. g., by Toluol
(boiling point, 111° C.), Xylol (137°), or Amylic Alcohol (129°).
A methodsof this description has been furnished by Squibb,’ and is
very worthy of recommendation. |

II. Squrss’s MetHop :—

“To 1.25 grams (19.29 grains) of well-burnt lime, contained in

* By operating in this way, the agglutination of the precipitate is avoided
elimination of the water Gee 6 Pa ee and the

* Ephemeris of Materia Medica, Pharmacy, ete., Brooklyn, N. Y., 1882, pp. 78, 105.

QUANTITATIVE ESTIMATION OF THE ALKALOIDS. 71

a 10-centimeter (4-inch) capsule, 30 cubic centimeters (1 fluid-
ounce) of hot water are added, and when the lime is slaked, the
mixture is stirred, and 5 grams (77.16 grains) of the powdered
cinchona’ are added, the mixture very thoroughly stirred, and
digested in a warm place for a few hours, or over night. The
mixture is then dried, at a low temperature, on a water-bath, rubbed
to powder in the capsule, and transferred to a flask of 100 cubic
centimeters (3.3 fluidounces) capacity, and 25 cubic centimeters
(0.8 fluidounce) of amylic alcohol added. The flask is afterward
corked, and digested in a water-bath at a boiling temperature,
with frequent, vigorous shaking, for four hours. It is then allowed
to cool, and 60 cubic centimeters (2 fluidounces) of stronger ether,
spec. grav. 0.728, added, and again shaken vigorously and fre-
quently during an hour or more. The liquid is now filtered
through a double filter of 10 centimeters (4 inches) diameter into
a flask of 150 cubic centimeters (5 fluidounces) capacity, and the
residue transferred to the filter. The flask is rinsed, and the
rinsings brought on to the filter with a mixture of 10 volumes of
amylic alcohol and 40 volumes of stronger ether, and the residue on
the filter percolated with 15 cubic centimeters (0.5 fluidounce) of
the same mixture, added drop by drop from a pipette to the edges
of the filter and surface of the residue. The residue is afterward
returned to the flask from whence it came, 30 cubic centimeters
(1 fluidounce) of the amylic alcohol and ether mixture added,
shaken vigorously for 5 minutes or more, and the whole returned
to the filter, and the residue again percolated with 15 cubic centi-
meters of the menstruum, applied drop by drop from a pipette, as
before. The filter and residue are now put aside, in order that
the latter may afterward be tested in regard to the degree of
exhaustion. |

‘The ether is now boiled off from the filtrate in the flask by means
of a water-bath, taking great care to avoid the ignition of the ether
vapor, and also to avoid explosive boiling, by having a long wire
in the fask. When boiled down as far as practicable in the flask,
the remainder is transferred to a tared capsule of 10 centimeters
(4 inches) diameter, and the evaporation continued on a water-
bath until the contents are reduced to about 6 grams (92 grains).
This is transferred to a flask of 100 cubic centimeters (3.3 fluid-
ounces) capacity, rinsing the capsule with not more than 4 cubic
centimeters (64 minims) of amylic alcohol, and adding the same
to the contents of the flask. 6 cubic centimeters (96 mimins) of
water and 4 cubic centimeters (64 minims) of normal solution of

1 A previous moistening of the bark with ammonia is also recommended,

72 CINCHONA BARKS.

oxalic acid are then added, and the mixture shaken vigorously and
frequently during half an hour. The mixture, while intimately
well mixed, is poured on to a well-wetted double filter of 12 centi-
meters (4.75 inches) diameter, and the aqueous solution filtered
from the amylic alcohol into a tared capsule of 10 centimeters (4
inches) diameter. The filter and contents are washed with 5
cubic centimeters (80 minims) of water, applied drop by drop from
a pipette to the edges of the filter and surface of the amylic alco-
hol. The amylic alcohol is then poured back into the flask, over
the edge of the filter and funnel, rinsing the last portion in with a
few drops of water. 10 cubic centimeters (160 minims) of water.
and 1 cubic centimeter (16 minims) of normal solution of oxalic
acid are now added, again shaken vigorously for a minute or two,
and the whole returned to the wetted filter, and the aqueous portion
filtered off into the capsule with the first portion. The amylic
alcohol is again returned to the flask, and the washings repeated
with the same quantities of water and normal oxalic acid solution.
When this has drained through, the filter and contents are
washed with 5 cubic centimeters (80 minims) of water, applied
drop by drop by drop from a pipette. The total filtrate in the
capsule is evaporated on a water-bath, at a low temperature, until it
is reduced to about 15 grams (241 grains) and this transferred to
a flask of 100 cubic centimeters (3.3 fluidounces) capacity, rinsing
the capsule with 5 cubic centimeters (80 minims) of water, and
adding this to the contents of the flask. 20 cubic centimeters (0.66
fluidounce) of purified chloroform are now first added, and then
6.1 cubic centimeters (98 minims) of normal solution of sodium
hydrate, and shaken vigorously for five minutes or more. While
. still intimately mixed by the shaking, the mixture is poured upon
a filter of 12 centimeters (4.75 inches) diameter, well wetted with
water. When the aqueous solution has passed through, leaving
the chloroform on the filter, the filter and chloroform are washed
with 5 cubic centimeters (80 minims) of water, applied drop by
drop. The chloroform solution is then, by making a pin-hole in
the point of the filter, transferred to another filter ig 10 centimeters
(4 inches) diameter, well wetted with chloroform, and placed over
a tared flask of 100 cubic centimeters (3.3 fluidounces) capacity.
The watery filtrate is washed through into the chloroform-wet
filter with 5 cubic centimeters (80 minims) of purified chloroform,
and when this has passed through into the flask, the chloroform-
wet filter is also washed with 5 cubic centimeters (80 minims) of
chloroform, applied drop by drop to the edges of the filter. When
the whole chloroform solution of alkaloids is collected in a flask,

QUANTITATIVE ESTIMATION OF THE ALKALOIDS. 73

the chloroform is boiled off to dryness in a water-bath, when the
alkaloids will be left in warty groups of radiating crystals, adhering
over the bottom and sides of the flask. The flask is then placed
on its side in a drying-oven, and dried at 100° C. (212° F.) to a
constant weight. The weight of the contents multiplied by 20
gives the percentage of the total alkaloids of the cinchona in an
anhydrous condition, to within 0.1 to 0.2 per cent., if the process
has been well managed.” |

If it is desired to avoid the use of ether, the alkaloids liberated
by lime may be taken up by xylol, toluol, or amylic alcohol at the
boiling temperature, and subsequently abstracted from these so-
_ lutions by means of dilute acids.

Estimation of Quinine.

“Into the flask containing the total alkaloids, after these have
been weighed, are placed 5 grams (78 grains) of glass, which has
been ground up in a mortar to a mixture of coarse and fine pow-
der, and 5 cubic centimeters (80 minims) of stronger ether added.
The flask is then corked, and shaken vigorously until, by means of
the glass, all the alkaloids have been detached from the flask and
ground up, in the presence of the ether, into fine particles. In this
way the definite quantity of ether which is large enough to dissolve
all the quinine that could possibly be present becomes entirely
saturated with alkaloids, in the proportion of their solubility, and
the solution will necessarily embrace all the very soluble ones as
the quinine.

“Two test-tubes are now marked at the capacity of 10 cubic cen-
timeters (160 minims) each, and a funnel and filter of 7 centime-
ters (2.8 inches) diameter placed over one of them. The filter is
well wetted with ether, and the mixture of alkaloids, ether and
glass poured on to it from the flask. The flask is rinsed out two
or three times on to the filter with fresh ether, the filter then washed,
and the glass percolated with fresh ether, applied drop by drop
from a pipette, until the liquid in the test-tube reaches the 10
cubic centimeter (160 minim) mark. The funnel is then changed
to the other test-tube, and the washing and percolation with ether
continued until the mark on the second test-tube is reached by the
filtrate. The contents of the two test-tubes are poured into two
small tared capsules, evaporated to a constant weight and weighed. ©
The first capsule will contain what may be called the ether-soluble
alkaloids, and if from the weight of these the weight of the residue
in the second capsule be subtracted, the remainder will be the

approximate weight of the quinine extracted from the 5 grams of 20

F

74 CINCHONA BARKS.

bark. These weights multiplied by 20 will give the percentage
of ether-soluble alkaloids, and of quinine.”

Another process, which is essentially that adopted by the Puar-
MACOPEIA GERMANICA (editio altera), but since improved by a slight
modification, is as follows:—

III. Twenty grams of the finely-powdered bark are repeatedly
and actively agitated with a mixture of 10 grams of ammonia
water (spec. grav. 0.960), 20 grams of alcohol (spec. grav. 0.830
to 0.834), and 170 grams of ether (spec. grav. 0.724 to 0.728),
and, after standing for a day, 120 grams of the clear liquid are
poured off. After the addition of 30 cubic centimeters of one-
tenth normal hydrochloric acid (containing 3.65 grams HCl in 1
liter) to the decanted liquid, the ether and alcohol are completely
removed by distillation or evaporation, and, if necessary, so much
hydrochloric acid added as is required to acidulate the solution.
This is then filtered, and the cooled liquid mixed with 3.5 cubic
centimeters of normal solution of potassiuny or sodium hydrate.
After the alkaloids have been separated, the solution of alkali is
added to the clear supernatant liquid until no further precipitate is
produced. The entire precipitate is finally collected upon a filter,
and gradually washed with a little water until the drops of liquid
escaping from the filter, when allowed to fall upon the surface of
a saturated neutral solution of quinine sulphate in cold water, no
longer produce a turbidity. After being allowed to drain, the
alkaloids are gently pressed between bibulous paper, then dried by
exposure to the air sufficiently to admit of bringing them into a
glass capsule, in which they are placed over sulphuric acid, and
finally completely dried in a water-bath. The weight of the dry
alkaloids, which, according to the requirement of the Pharmacopeeia
Germanica, should amount to not less than 0.42 gram, or 3.5 per
cent., does not relate to 20 grams of the powdered bark, but only
to 12 grams of the same, since only 120 cubic centimeters of liquid
were decanted.

The alkaloids, which by this method are obtained somewhat less
pure than by the preceding, may again be dissolved in hydro-
chloric acid, precipitated by alkali, then taken up by chloroform or
ether, and, after the evaporation of the latter, weighed.’

The method of De Vrij, as adopted by the Unrrep SratEs
Puarmacopata (Sixth Decennial Revision, 1880), for the assay of
Cinchona barks, is as follows :— _ oe ea

1 Compare Prollius, Archiv, der Pharm., e : (1881), p. 86; Biel, Zdzd, 220 ( 1882), Pp:
355; and H. Meyer, /é7d, 220, (1882), pp. 721, 812. The weight of the residue remain-

ing upon the evaporation of the ether corresponds approximately to the amount of
quinine, — .

QUANTITATIVE ESTIMATION OF THE ALKALOIDS. 75

1. For Torart ALKALOIDS.

IV. “Twenty grams of the cinchona, in very fine powder, and °
fully dried at 100° C. (212 F.), are thoroughly mixed with 5 grams
of lime which has previously been made into a milk with 50 cubic
centimeters of distilled water, and the mixture completely dried at
a temperature not above 80° C. (176° F.). The dried mixture is
digested with 200 cubic centimeters of alcohol, in a flask, near the
temperature of boiling, for one hour, and, when cool, the mixture
poured upon a filter of about 15 centimeters (6 inches) diameter.
The flask is rinsed and the filter washed with 200 cubic centimeters
of alcohol, used in several portions, and allowing the filter to drain
after the use of each portion. To the filtered liquid enough diluted
sulphuric acid is added to render the liquid acid to test-paper, any
resulting precipitate (calcium sulphate) allowed to subside, the
liquid decanted, in portions, upon a very small filter, and the residue
and filter washed with small portions of alcohol. The filtrate is
then distilled or evaporated, to expel all the alcohol, allowed to
cool, passed through a small filter, and the latter washed _ with dis-
tilled water, slightly acidulated with diluted sulphuric acid, until the
washings are no longer made turbid by solution of sodium hydrate.
To the filtered liquid, concentrated to the volume of about 50 cubic
centimeters, when nearly cool, enough solution of sodium hydrate
is added to render it strongly alkaline. . The precipitate is collected
on a wetted filter, allowed to drain, and washed with small por-
tions of distilled water (using as little as possible), until the wash-
ings give but a slight turbidity with test-solution of barium chloride,
and the filter drained by laying it upon blotting or filter papers
until it is nearly dry. 3 is

The precipitate is then carefully detached from the filter, and
transferred to a weighed capsule ; the filter is washed with distilled
water, acidulated with diluted sulphuric acid, the filtrate made alka-
line with solution of sodium hydrate, and, if a precipitate results,
this is washed on a very small filter, allowed to drain well, and also
transferred to the capsule. The contents of the latter are now
dried, at 100° C. (212° F.), to a constant weight, cooled in a dessi-
cator, and weighed. The number of grams multiplied by 5 equals
the percentage of total alkaloids in the cinchona.” _ |
The U.S, Pharmacopeeia recognizes under “ Cinchona” the bark
of any species of cinchona containing at least 3 per cent. of its
peculiar alkaloids, while the “ Cinchona Flava” (Calisaya Bark) —
and “Cinchona Rubra” (Red Bark) are required to contain at least
2 per cent. of quinine. — oe

76 CINCHONA BARKS.

2. For QUININE.

“To the total alkaloids from 20 grams of Cinchona, previously
weighed, distilled water, acidulated with diluted sulphuric acid, is
added, until the mixture remains for 10 or 15 minutes after diges-
tion just distinctly acid to test-paper. It is then transferred to a
weighed beaker, rinsing with distilled water, and adding of this
enough to make the whole weigh 70 times the weight of the alka-
loids. Solution of sodium hydrate, previously well diluted with
distilled water, is now added, in drops, until the mixture is exactly
neutral to test paper, digested at 60° C. (140° F.), for 5 minutes,
then cooled to 15° C. (59° F.), and maintained at this temperature
for half an hour. If crystals do not appear in the glass vessel, the
total alkaloids do not contain over 8 per cent. of their weight of
quinine (corresponding to 9 per cent. of crystallized sulphate of
quinine). If crystals appear in the mixture, the latter is passed
through a filter not larger than necessary, prepared by drying two
filter papers of 5 to g centimeters (2 to 3.5 inches) diameter, trim-
ming them to an equal weight, folding them separately, and placing
one within the other so as to make a plain filter fourfold on each
side. When the liquid has drained away, the filter and contents
are washed with distilled water of a temperature of 15° C. (59° F.),
added in small portions, until the entire filtered liquid weighs 90
times the weight of the alkaloids taken. The filter is then dried,
without separating its folds, at 60° C. (140° F.), to a constant
weight, allowed to cool, and the inner filter and contents weighed,
taking the outer filter for a counter weight. To the weight of
efloresced quinine sulphate so obtained, 11. 5 per cent. of its
amount is added (for water of crystallization), and 0.12 per cent.
of the weight of the entire filtered liquid added (for solubility of
the crystals at 15° C. or 59° F). The sum in grams multiplied by
5 equals the percentage of crystallized quinine sulphate equivalent
to the quinine in the cinchona.”

For the preparation of the extracts and tinctures, as also for the
direct application of the bark in dispensing, it suffices to know the
total amount of alkaloids. One must furthermore convince him-
self that quinine is present, by dissolving 1 part of the crude alkaloid
in the smallest possible quantity of hydrochloricacid, precipitating the
bases with caustic soda, decanting the liquid, and agitating the
deposit with 20 parts of ether. The etherial solution is allowed to
_ €vaporate, and 1 part of the residue boiled with 300 parts of water

and filtered, when, upon cooling, some quinine Separates out. If

QUANTITATIVE ESTIMATION OF THE ALKALOIDS. 77

to 5 parts of the clear liquid there be added 1 part of chlorine
water, it must assume a beautiful green color upon the direct
addition of a few drops of ammonia water.

If it is desired to ascertain how much quinine is contained in a
mixture of alkaloids, the latter must be accurately neutralized with
either dilute sulphuric acid or with tartaric acid, as above described;
the corresponding salts of quinine, on account of their sparing
solubility, may readily be separated from those of the associate
alkaloids."

The solutions of quinine and of cinchonidine, and their salts, de-
viate the plane of polarization to the left, in proportion to the amount
of these bases contained therein. The solutions of cinchonine and
quinidine (conquinine) show an opposite behavior. With consid-
eration of these facts, De Vrij has founded an optical method for
the quantitative estimation of these alkaloids,? which, as further
developed by A. C. Oudemans;, affords in very experienced hands
good results,

A more recent method adopted by De Vrij* for the quantitative
estimation of quinine consists jn precipitating the latter in the form
of herapathite, 4C,,H,,N.O, + 3H,SO, + 2HI + 4l +3H,O, by
means of a solution of iodosulphate of chinoidine.

1. PREPARATION OF THE IoposULPHATE OF CHINOIDINE.—One part
of commercial chinoidine and two parts of benzol are heated to-
gether on a water-bath, whereby a solution of chinoidine in benzol
is obtained. The clear solution, after cooling, is poured off from
the insoluble part and agitated with an excess of diluted sulphuric
acid, which, combining with the chinoidine dissolved in the benzol,
yields a reddish-yellow solution of acid sulphate of chinoidine. To
this clear solution, contained in a capsule, a solution of one part ot
iodine and two parts of potassium iodide in fifty parts of water is
slowly added, with continuous stirring, so that no part of the solu-
tion of chinoidine comes in contact with an excess of iodine. One
part of iodine is required for two parts of chinoidine contained in
the acid solution. By this addition an orange-colored flocculent
precipitate of iodosulphate of chinoidine is formed, which, either
spontaneously or by aslight elevation of temperature, collects into
a dark brown-red, resinous substance, while the supernatant liquid

? Compare Flickiger, Pharmaceutische Chemie, 1878, p. 414-

oF Pharm. Fourn., 11 (1871), 521, 642. es oe Co ee eo

8 Pouvoir rotatoire aphcitane des principaux alkaloides des Quinquina. Archives néer-
fash aesee S875) WR LINE? is oe eee a ee ee

4 Pharm. Journ., X11 (1882), p.601. A method for the rapid quantitative estimation of
quinine is still wanting. ae . LO ee

78 CINCHONA BARKS.

becomes clear and slightly yellow. This liquid is poured off," and
the resinous substance is washed by heating it on a water-bath
with distilled water ; after washing it is heated on a water-bath
until all the water has evaporated. It is then soft and tenacious at
the temperature of the water-bath, but becomes hard and brittle
after cooling. One part of this substance is now heated on a water-
bath with six parts of alcohol of ninety-two or ninety-four per cent.,
and is thus dissolved, and the solution allowed to cool. On cooling,
a part of the dissolved substance becomes separated. The clear,
dark-colored solution is evaporated on a water bath and the residue
dissolved in five parts of cold alcohol. This second solution leaves
a small portion of insoluble substance. The clear solution obtained
by the separation of this insoluble matter, either by decantation or
filtration, constitutes the reagent employed for the qualitative and
quantitative estimation of crystalizadble quinine.

2. EstimaTIon oF QuintnE.—To determine the quantity of qui-
nine contained in the mixed alkaloids obtained from a cinchona
bark, one part (one gram) of these alkaloids is dissolved in twenty
parts of alcohol, of ninety-two or ninety-five per cent., containing
1.5 percent. of H,SO,, and this solution is diluted with fifty parts
of pure alcohol. From this solution the quinine is separated at the
ordinary temperature, by adding carefully, by means of a pipette,
the above-mentioned solution of iodosulphate of chinoidine as long
as a dark brown-red precipitate of iodosulphate of quinine (era-
pathite) is formed. As soon as all the quinine has been precipitated,
and a slight excess of the reagent has been added, the liquid
acquires an intense yellow color. The beaker containing the liquid
with the precipitate is now covered by a watch-glass, and heated
until the liquid begins to boil and all the precipitate is dissolved.
The beaker is then left to itself, and, in cooling, the herapathite is
separated in the well-known beautiful crystals. After twelve hours’
rest, the beaker is weighed, to ascertain the amount of liquid, which
is necessary in order to be able to apply later the necessary cor-
rection, the herapathite being very slightly soluble in cold alcohol.
The clear liquid is poured off, as far as possible, on a filter, leaving
most of the crystals in the beaker, which is now weighed again, to
ascertain the amount of liquid, and the weight noted. The few
crystals on the filter are now washed down into the beaker, and as
much alcohol added as is necessary to redissolve all the crystals at
the boiling point. The object of this redissolving is to be absolutely

rae prevent the use of an excess of iodine, the amount of the latter is intentionally
made insufficient to precipitate all the chinoidine in the form of iodosulphate. Therefore
the liquid still contains chinoidine, which can be obtained in a very pure state if a little
sulphurous acid is added before precipitating the alkaloid by sodium hydrate. _

MANUFACTURE OF QUININE. 79

certain that by surface attraction no trace of iodosulphate of
cinchonidine has adhered to the crystals of herapathite. After
perfect cooling, the weight of the beaker is ascertained again, the
crystals of herapathite carefully collected on a small filter, and the
empty beaker again weighed. The difference in weight will indi-
cate the amount of liquid, which is added to that of the first liquid,
and from the sum of this addition the necessary correction is cal-
culated. If the operation is effected at a temperature of 16° C.
(60.8° F.), the weighed quantity of the two liquids will indicate the
correction if multiplied by 0.125 and divided by roo. If the tem-
perature be lower or higher, the solubility of herapathite at that
temperature must be ascertained by experiment, which can easily
be performed by a standard solution of hyposulphite (thiosulphate)
of sodium, as 21.58 parts of iodine found by this reagent indicate
100 parts of herapathite. The herapathite collected on the filter
is thoroughly washed with a saturated alcoholic solution of pure
herapathite, and after this washing is completed the liquid retained
by the crystals is expelled as muchas possible by slightly knocking
the side of the funnel. The filter is then taken from the funnel
and laid upon blotting paper, often renewed, to take away as
quickly as possible the still adhering liquid. As soon as the filter
is air-dry, the crystals of herapathite can be completely removed
from the filter and dried on a water-bath in one of a couple of large
watch-glasses closing tightly upon each other, so that the weight of
the substance contained in the glass may be taken without the
access of the air. If, after repeatedly weighing, the weight remains
constant, it is noted, and to itis added the product of the calculated
correction. The sum of this addition is the total amount of iodo-
sulphate of quinine obtained from the mixed alkaloids subjected to
the operation, and from this weight the amount of quinine can be
calculated from Jérgensen’s formula: 4C,,H,,N,O, + 3H,SO, +
2HI + 1,. According to this formula one part of herapathite, dried
at 100° C, (212° F.), represents 0.55055 parts of pure anhydrous
quinine.

SECTION XV.
MANUFACTURE OF QUININE.

The preparation of quinine and the other alkaloids on a manu-
facturing scale consists likewise in separating them from the com-
pounds in which they are contained in the bark, by means of lime.
From the moist mixture, containing lime, the bases are extracted by
means of warm shale oil, brown coal-tar oil, or petroleum of a low

80 CINCHONA BARKS.

boiling point, or also by means of alcohol. In the latter case the
alcohol is distilled off,* the residue taken up bya dilute acid, and
the alkaloids precipitated from the solution by means of caustic
soda. From the solutions of the alkaloids in the hydrocarbons the
bases may be still more conveniently taken up by dilute acids, and
precipitated therefrom by caustic soda. If the washed precipitates
are dissolved, by the aid of heat, in dilute sulphuric acid, avoiding
an excess of the latter, there separates, upon cooling, neutral and
quite pure sulphate of quinine, while the sulphates of the other
alkaloids, in consequence of their much greater solubility, remain
for the most part in the mother liquid. The purification of the
sulphate of quinine is effected by recrystallization.

In India, Broughton (1870), in consequence of an impulse given
by Markham, has taken into consideration the separation of the
alkaloids in the cheapest manner. According to the suggestion of
De Vrij (1872), which has been carried out since 1873 by Wood,
the bark is extracted with water, to which some hydrochloric acid
has been added, and the bases precipitated by means of caustic
soda. The precipitate, after being washed, is dissolved in dilute
sulphuric acid, again precipitated by caustic soda, and subsequently
washed and dried. In 1876 the average percentage composition
of such a “ Febrifuge,’* which had been prepared by Wood, in
Sikkim, from the bark of Cinchona succirubra, was found to be as
follows: Cinchonine, 33.5; cinchonidine, 209.0; amorphous alka-
loids, 17.0; quinine, 15.5; and coloring matter, 5.0. It is now
purified to such an extent as to form a white crystalline powder.
In 1877 it was calculated by the English Government that the
‘‘Febrifuge,” with consideration of all expenses, could be placed at
but little more than 60 marks (about fifteen dollars) per kilogram.
It should accordingly be presumed that great significance would
be attributed to this cheap remedy for India; it appears, however,
at least in Madras, to enjoy no favor.

? Hereby cinchonine crystallizes out, when it is present in abundant amount.

? Also designated by De Vrij as “ Quinetum.” Compare Jakresbericht der Pharm.,
1876, p. 142, and 1878, p. 111, as also the Blue Books, 1870-1875, fol. 126. ‘“ Febrifuge’’
is now being made at Mungpoo, British Sikkim ; 6196 pounds of it were used in 1881,
in the Government hospitals and dispensaries in India.

HISTORY OF THE CINCHONA BARKS TO THE YEAR 1737. 81

SECTION XVI.
HISTORY OF THE CINCHONA BARKS TO THE YEAR 1787.

The agreeably odorous legumes of the Peru balsam tree, Tolui-
fera Pereirze Bazllon (Myroxylon Pereire AZotzsch), and to a greater
degree the very similar legumes of the much more widely distrib-
uted Myroxylon peruiferum Z. //., have presumably been for a long
time in medicinal use in Central America and in the northern portion
of South America.’ The latter in the northwestern part of South
America are still called Pépitas (kernels) de Quina-guina, Quino-
guino or Kina-kina? According to Chifflet?and Joseph de Jussieu,
as also according to Ch. M. de la Condamine,‘ the febrifuge bark
had been referred to the same tree, and it is for this reason that
the same designation has been transferred to it, which has finally
become simplified into Quina, Kina, or China, In the South Amer-
ican languages, by a duplication of the sound, a superior quality of
the respective substance is emphasized. Although the designation
“Quina-quina” was adopted by the Europeans, the Spanish ex-
pression, “ Cascarilla,” obtained by the natives, even in Condamine’s
time, the supremacy.

From the time of the first Spanish invasion of Peru, in 1513, no
proofs of an early acquaintance of the natives with Cinchona bark have
been transmitted, although Arrot § and Condamine, as also Jussieu,
heard it stated in Loxa that such was the case, and, in concurrence
with Ruiz and Pavon, found the reports worthy of credence. Ac-
cording to these statements, the Peruvians had kept the Spaniards
uninformed regarding the medicinal virtues of the Cinchona, and
in Loxa, e. g., they had been known from a much earlier period
than in Lima. The acceptance of this statement appears to have
been generally prevalent, at least toward the end of the seventeenth
century, as the reminiscences of the past ages were still more
active. That precise statements are wanting 1s explained by the
entire deficiency of written documents from the old kingdom of

the Incas.

1 Compare Fliickiger’s Pharmakognoste, 24 edition, pp. 124, 131, 132, 136.

2 Weddell, Hist. nat. des Quinguinas, pp. 15, 22.—Cross, Blue Book, 1866, p. 276.

3 Pulvis febrifugus Orbis Americant ventilatus. Brussels, 1653. Cite

4 Weddell, loc, cit. The noble Parisian druggist, Pierre Pomet, made honest endeav-
ors to obtain for his “ Histoire générale des Drogues,” which appeared in 1694, more ac-
curate information regarding the trees which furnish the cinchona barks. The vague
reports which he procured evidently relate also to Myroxylon. “E fe

5’ Phil. Transactions, vol. XL, for the years 1737 and 1738. London, 1741, No. 446.
An account of the Peruvian or Jesuit’s bark.” soe :

82 CINCHONA BARKS.

Wellcome* shares the opinion, which he heard from the natives,
that their ancestors were acquainted with the Cinchona bark before
the Spanish conquest, although it has not been met with as yet in
the ancient tombs of the Incas, as, ¢. g., is the case with coca
leaves. The reverse conviction, which is universally prevalent, is
explained by Wellcome from the fact that it was the endeavor of
the Spanish conquerors to appropriate to themselves all such hon-
ors. Digressive views have, however, also become current. Sincethe
Peruvians adhere with the greatest tenacity to transmitted customs,
and even at the present time do not employ Cinchona, but, on the
contrary, regard it with fear, Humboldt? concludes that the case
must have been similar with their ancestors. Markham,? who
traveled through Peru in 1859, confirms the statement that the
wallets of the native itinerant doctors,‘ who, according to a very
ancient custom prevailing throughout the entire country, travel
from the mouth of the Rio de la Plata to Ecuador, do not contain
cinchona bark, although these still highly celebrated “ Botanicos
del Imperio de los Incas,” also called Chivitmanos or Collahuayas,
live in the West Bolivian province of Munecas, in the region of
the best Cinchona trees. There prevails in general, as Péppig
(1830) and Spruce (1859) found,’ precisely in the Cinchona dis-
tricts, a strong repugnance to this remedy, even in Guayaquil.

The most probable view, however, is afforded that the earliest
knowledge of Cinchona remained confined to the neighborhood of
Loxa. Although the Spaniards were firmly located there as early as
the middle of the sixteenth century, their earliest authors from that
district are silent in regard to the Cinchona, even to the commence-
ment of the seventeenth century. Here, in the village of Malaca-
tos, a traveling Jesuit is said to have been cured by a cacigue ® of
a fever by means of cinchona, and to have extended a knowledge
of the remedy. To the same place and the same remedy the
Spanish corregidor of Loxa, Don Juan Lopez de Canizares, is said
to owe his recovery from intermittent fever, in 1630.

1 Proc. Amer. Pharm. Assoc., 1879, p. 830.

? Page 60 of the essay mentioned on p. 24, Note 2. Also a manuscript seen by Ch.
P. von Martius, entitled ‘‘ Memoria sobre el estado de las Quinas en particular sobre la
de Loxa,” which was written between the years 1803 and 1809, notices the intense preju-
dice of the Indians against the use of the “ Cascarilla.”—Bu//etin der Miinchener Akad-
emie, 1846, No. 55; Gelehrte Anzeigen, p. 342.

_* Clements R. Markham. ‘ Two Journeys in Peru,” 1862, 2. The German Transla-
tion, Leipsic, 1865, 186.

* Compare Beck, in Petermann’s Geogr. Mittheilungen, 1866, p. ; also Markham,

“ Peruvian Bark,”’ 162. el hes heel Hg
_ > Compare also the Blue Book, 1863, p..75.
® Priest of the worshipers of the sun. _-

HISTORY OF THE CINCHONA BARKS TO THE YEAR 1737. 83

On the 11th of August, 1621, Ana de Osorio, widow of Don
Luis de Velasco, married Don Luis Geronimo Fernandez de Ca-
brera y Bobadilla, of Madrid, the fourth Count of Chinchon. The
year 1628 brought to the Count the highest distinction that was at-
tainable in Spain—he was appointed Viceroy of Peru, z. e., regent
of the entire Spanish territory in South America. On the 14th of
January, 1629, the vice-regal pair entered Lima." As the Count-
ess, in 1638, was prostrated by a fever in the palace at Lima, the
same corregidor of Loxa sent Cinchona bark to the vice-regal
physician, Dr. Juan de Vega. In the treatment of the Countess
-Chinchon the virtues of the remedy were also confirmed, so that
she caused it to be distributed in Lima. Even here the powdered
bark acquired the name of Polvo de la Condesa (Countess Powder).
A knowledge of this febrifuge must have very soon penetrated
into Spain, even if it may be doubted that this took place as early
as the year 1632, before the cure of the Countess, as has been
stated by Villerobel. In 1639 Cinchona bark certainly appears to
have been used in Alcala de Henares, near Madrid.*

Perhaps, also, with relation to the first Jesuit treated therewith at
Malacatos, the bark soon received the name of Folvo de les
Fesuitos, as this Order, especially through the Cardinal connected
therewith, Juan de Lugo, residing at Rome, began to zealously
adopt the new remedy. As Nicolas Lémery declared, the Jesuits
derived great profit therefrom. In the meantime, however, the
same physician, Juan de Vega, on the occasion of the return of the
viceroy to Spain, had, as early as 1640, likewise taken Cinchona
with him, and, e. g. sold the same in Seville at 100 vea/s (about 100
dollars) per pound.

The Cardinal de Lugo, Attorney-General of the Order of Jesuits,
had, as it appears, the superintendence of a pharmacy belonging
to them, but permitted, however, also in his palace the distribution
of cinchona bark to the indigent sick, which, therefore, became
known as “Pulvis eminentissimi Cardinalis de Lugo,” or “ Pulvis

1 With regard to the Count Chinchon, who conducted the Government of Peru until
the 17th of December, 1639, compare also Fliickiger’s Pharmakognosie, p. 85.

2 With relation to the earliest history of the cinchona barks, compare further the publi-
cations of H. von Bergen, Weddell and Markham, which are mentioned by name in
Section 18 of this work.

3 H. von Bergen, 84, 90. : :

4 Sebastiano Bado. Anastasis, Corticis Peruvia, seu Chine Chine defensio. Genoa,
1663, 202. ae ee eae

5 Chiffletius, 1. c. According to the Biogr. Universelle, Paris, 1821, Juan de Lugo was
born in 1583, at Madrid, entered the Order of the Jesuits in 1603, was made a cardinal
in 1643, and died at Rome in 1660. Also the same, according to Lorenzo Ca :
Mem. storiche de’ Cardinali della Santa Romana Chiesa V1. (Roma, 1797) 47. —

84 CINCHONA BARKS.

patrum.’’* In 1649, de Lugo, in passing through Paris, recom-
mended the remedy to the Cardinal Mazarin for the young Louis
XIV, who was sick with a fever. The Jesuits in Rome received
at this time a quantity of Cinchona from their Provincial from
America, who, in 1643, went to the Chapter of the Order at
Rome.? Michael Belga at this time likewise brought Cinchona from
Lima to Antwerp and Brussels.

Belgian physicians likewise contributed materially to the knowl-
edge and distribution of Cinchona. Through Chifflet, physician
to the Archduke Leopold, of Austria, Governor of the Netherlands,
this was effected in a publication which appeared at Brussels, in
1653 (or 1651?), entitled “ Pulvis febrifugus Orbis Americani ven-
tilatus.” Although Chifflet prized the Cinchona bark as a marvel
of his time, he recommended it, however, so mildly that a heated
controversy® arose, in which, e. g. Glantz (1653), an imperial phy-
sician at Ratisbon, as also Godoy, a physician of the Spanish King,
and Moreau and Plempius (1655) stood and wrote in Chifflet’s de-
fence. As active opponents of these physicians there appears
decidedly in favor of the bark the Jesuit, Honoratius Faber, Fonseca,
physician to Pope Innocent II, Sebastian Bado, of Genoa, and
especially, in 1653, Doctor Roland Sturm,} of Louvain. The latter
communicates also the detailed directions for its use in 1651, which
the apothecaries of Rome were accustomed to give with the bark
when dispensing it.®

The Cinchona began to be known in England about the year
1655, and in 1658 was repeatedly advertised for sale in the “ Mer-
curius Politicus,” one of the earliest newspapers of England, by
the Antwerp merchant, James Thompson, as “the excellent powder
known by the name of the Fesuits Powder.” Brady and Willis, two
distinguished English physicians, prescribed Cinchona bark in the
year 1660.’ ;

It is very remarkable that Cinchona bark is not contained in the
Pharmacopeeia of the Hague, of the year 1659; in 1664 it was
designated a dutiable product at Lyons.

* Roland Sturm. Febrifug? Peruviani vindiciarum pars prior: Pulveris historiam
complectens ejusque vires et proprietates . . . . . exhibens. Delphis, 1659, 12°.

2 Chiffletius, 1. c.; Sprengel, Geschichte der Arznayhunde, IV (Halle, 1827), 513.

* The more complete title of these older publications is given by H. von Bergen,
pp- I-72; also in Mérat et De Len’s Dictionnaire de Mat. Med. V (1833), p. 632.

# Page 83, note 4. 8 Note 1. dae

* “Modo di adoprare la corteccia chiamata della febre,” reprinted in Fliickiger and

Hanbury’s Pharmacographia, second edition, p. 343- He . ;
7 See Pharmacographia, second edition, Pp. 344.

_ * Martiny, Rohwaarenkunde, | (1843), p. 3.

HISTORY OF THE CINCHONA BARKS TO THE YEAR 1737. 85

In Germany, “ China Chine” is met with in the pharmaceutical
tariffs of Leipsic and Frankfort for the year 1669. According to
the latter, one “quint” (one-eighth of an ounce) cost 50 kreuzers
(about 38 cents), whereas the same amount of opium was quoted
at 4 kreuzers, camphor at 2 kreuzers, and balsam of Peru at 8
kreuzers.

It is conceivable that at that time other barks possessing a bitter
taste might be mistaken for Cinchona bark. An indeed very re-
markable example of this kind is afforded by the Cascarilla bark*
from Croton Eluteria, a small tree belonging to the family of
Euphorbiacee. This drug from the West Indies, which possesses
a bitter, but at the same time, however, a strongly aromatic taste,
made its appearance in Germany toward the close of the seven-
teenth century, under the name of Chzna nova; but, as it appears,
soon passed into oblivion, and at the beginning of this century the
same name was again bestowed upon an entirely different bark,
namely, that of Cascarilla magnifolia (mentioned on p. 48). It
may, indeed, be accepted that in the meantime still other barks
were frequently confused with or used to adulterate the Cinchona
barks.”

The further distribution of Cinchona was advanced in a high
degree by Robert Talbor, a physician who emanated from a phar-
macy in Cambridge, and who, in 1672, made himself known
through the publication of “ Pyretologia, a rational account of the
cause and cure of agues,’ in which also “ Jesuits’ Powder” is spoken
of. In 1678 Talbor was appointed physician to King Charles II,
and also made a knight; in 1679 he treated the King at Windsor
with Cinchona, and received then also not less favor at the French
Court. It is remarkable that Talbor knew how to envelop his
cures with such secrecy that he was able to make his chief remedy,
cinchona bark, contribute in the most successful manner to his
personal profit. As, in 1681, after Talbor’s death, King Louis XIV
caused the composition of the remedy to be made known, cinchona
bark was revealed as its chief constituent, and now attracted the
renewed attention of physicians.* |

Aworthy successor of Talbor, Nicolas Blegny,’ likewise physi-

1 Flickiger, Pharmakognosie, second edition, p. 573.

2 Compare Fliickiger, Pharmakognosie, 2d edition, under Quassia, p. 461; Pharma-
cographia, 2d edition, p. 1066—Quina de Caront, ee

3 Mérat et De Lens, Dictionnaire de Matiétre médicale, V (1833), 627.

4 More complete information regarding Talbor is contained in Pharmacographia, 24
edition, pp. 344 and 766. . ai:
8 Compare further regarding the character of this swindler, who followed the occupa-
tion of physician and apothecary in Paris, until, in 1686, he was placed in the I
Grave, Etat de la Pharmacie en France. Mantes, 1879, p. 179. Le

86 CINCHONA BARKS.

cian to Ludwig XIV, dedicated in 1682 to the “‘Reméde Anglais,”
an oft-quoted pamphlet. The first physician of the King, Antoine
d’Aquin, and Fagon, physician to the Queen, were commissioned
to receive from Talbor the secret recipe.’ Fagon, in 1704, assigned
to the Franciscan botanist, Charles Plumier, who was to undertake
his fourth journey to South America, the commission to determine
the origin of the Cinchona barks. Plumier died, however, at
Cadiz.’

In the meantime, living Cinchonas had already found their way to
London, or were cultivated there from seed,? and for a not unin-
teresting short report on the “Peruvian Bark”’ or “ Jesuits’ Bark,”
we are indebted to the Scotch surgeon, William Arrot, who, about
the year 1730, had made observations in Loxa. He described
accurately the work of the Cascarilleros, and, even at this time, ex-
pressed solicitude regarding the extermination of the trees.

SECTION XVII.
MORE RECENT HISTORY OF THE CINCHONA BARKS.

The knowledge of the Cinchonas was introduced in a scientific
spirit by the otherwise celebrated expedition of the Paris Academy.
In their commission, the astronomers, Charles Marie de la Conda-
mine, Bouguer and Godin, were occupied, from the year 1736 to
1744, in measuring the arc of a degree in Peru. At the same time
improving every opportunity for the advancement of other branches
of natural science, Condamine, in accordance with the directions of
Joseph de Jussieu, on the 4th of February, 1737, on the journey
from Quito, by way of Cuenca, to Lima, observed one of the Cin-
chona trees on the mountain of Cajanuma, 21% leagues southward
from Loxa, which Arrot (page 81) had also already named. In
the following year Condamine’s’ description and figure of his
“arbre de quinquina” was laid before the Paris Academy, and was
published by the latter in 1740. According to Howard, this first

1 Les admirables gualitez du Kinakina, confirmées par plusieurs expériences. Paris,
Jouvenel libraire, 1089. 164 pages, in 8°. (Without the name of the author).
2 Cap, Etudes (mentioned on p- 47).

* According to the short notice in Semple, Memoirs of the Botanic Garden at Chelsea,
belonging to the Society of Apothecaries in London, 1878, p. 16: “In 1685, August 7th,
I went to see M. Watts, Keeper of the Apothecaries’ Garden of Simples at Chelsea,
where there is a collection of innumerable variety of that sort; particularly .
the tree bearing Jesuits’ bark, which had done such wonders in quartan agues.”

* See p. 81, Note 5.

’ Hist. de l'acad. roy. des sciences, ann, 173 , avec les mém. de math. et de phys. pour
_ la méme année. Pacle, tees pp. 226-243. es ea

. . .

MORE RECENT HISTORY OF THE CINCHONA BARKS. 87

described Cinchona tree is the Cinchona officinalis, Var. a or
Uritusinga of the present day. Jussieu, the botanist of the above-
mentioned French expedition, who was moreover also an engineer
and physician, collected likewise, in 17 39, near Loxa, a Cinchona—
the subsequent C. pubescens Vah/. Mutis also soon received what
was presumably the same, from the same district, and sent it to
Linnzus. The latter, in honor of the Countess Chinchon, as shown
on page 18, did not name the genus Chinchona, but CGnchona.
This orthography has also found universal acceptance, and, in 1866,
was even sanctioned by a resolution of the International Botanical
Congress at London.*’ Markham, to whom we are indebted for a
handsome publication,’ dedicated to the memory of the Countess
Chinchon, had effectuated that the English authorities at first made
use of the orthography Chinchona.

In the beginning of the eighteenth century the commerce in
barks at Loxa was already much developed; and it was necessary
for good barks to be recommended by a certificate of their origin
from this locality. In Payta (5°S. lat.), the nearest port, an exam-
ination of the bark for adulterations was already established.

In 1752 the “ Superintendente general de la moneda,” superin-
tendent of the mint at Santa Fé, Don Miguel Santisteban, was
delegated to go to Loxa, in order to organize the commerce in Cin-
chona bark. He reported thereon, in 1755, to the respective ad-
ministration, ‘Estanco de Cascarilla,’ and added that he had met
on the way with Cinchona trees. Among these, according to
Triana,* was also the present Cinchona cordifolia, which Santisteban
had found between Pasta and Barruecos, in the southwestern part
of New Granada. He brought specimens of the plant with him
for Mutts, who visited Santa Fé in 1761.

José Celestino Mutis, who was born at Cadiz in 1732, arrived in
1760 at Carthagena, in New Granada, with the newly-appointed
viceroy, the Marquis de Vega, as his physician,’ and soon found an
opportunity to make application of his botanical knowledge in the
exploration of the flora of that country. He first started from

1 Howard, Observations on the present state of our knowledge of the genus Ciachona.
yeep a the Internat. Horticult. Exhibition and Botanical Congress, held in

London, 1866, p. 195-223. Abstracted in the Archiv der Pharm., 130 (1867), p. 91, and
more completely in Buchner’s Refertor fiir Pharm., 17 (1868), p. 65.
2 Title under section 18, No. 22.

& Pharmacographia, second edition, p. 345.

4 Etudes, title under section 18. Also Humboldt, p. 113, of the essay mentioned on
p- 24, note 2. a co

5 In 1772 Mutis entered a religious order, and afterward became a teacher of mathe-
matics and astronomy at Santa Fé de Bogota, where he died, on the 2d of September,

88 CINCHONA BARKS.

Cacota and La Montuosa, near Pamplona, then, since 1782, from
Real del Sapo and Mariquita, at the foot of the Quindia, and,
finally, since 1784, at the head of an “Expedicion botanica del
Nuevo Reino de Granada,” in Santa Fé.

In the meantime (1776) Don Sebastian José Lopez Ruiz’ pre-
sented to the viceroy in Santa Fé a Cinchona, which, according to
Triana, was Cinchona lanctfolia, or Tunita, in the language of
that country. This species (p. 18) grows only in the eastern dis-
trict of the Cordilleras of Bogota. Mutis himself, before his re-
moval to the capital, explored only the western chain of mountains
at the upper part of the Magdalena River, near Mariquita, Tena,
and Honda, where, according to the experience of Triana, no true
Cinchona grows. The pretended Cinchona found by Mutis in this
district, in the year 1771, is rather simply one of the species of
Cascarilla comprehended by him under the name of C. oblongifolia,
probably Cascarilla magnifolia (compare p. 48). The Cinchona
collected by Mutis, in 1766, in the province of Pamplona, north-
ward from Santa Fé, is also, according to Triana, only Cosmzbuena
obtustfolia Ruiz et Pavon, and by no means a true febrifuge tree.

All of the true Cinchonas which are contained in the ‘ Quino-
logia de Bogota,” of Mutis, under the names of C. lancifolia and
C. cordifolia, were discovered by Santisteban, Lopez Ruiz, or his
nephew, Sinforoso Mutis, and the pupils of the former; nota single
one by Celestino Mutis himself.

Triana produces valid reasons for this statement, so that the
contention for priority, which at that time was carried on with
much animosity between Mutis on the one hand and Ruiz and
Pavon on the other, together with the adherents of both parties, is
herewith brought to a close. In consequence of Mutis having
transferred the name of Red Cinchona, Ouina, or Cascarilla colo-
rada, or roja to the worthless bark of the trees which he named
Cinchona oblongifolia, containing no quinine, whereas it properly
belongs only to the bark of C. succirubra, rich in alkaloid, a com- —
plication ensued, which was first removed by the discovery of qui-
nine, in the year 1820.

After the Cinchona barks, since about the year 1640, had only
been exported from Peru and Ecuador of the present day, through
the activity which Mutis and his pupils developed in the north-
western part of the South American Continent, the attention of
botanists and merchants was directed to the Cinchona trees of this

_* This otherwise insignificant man appeared beni: pean of Mutis in the publica-
tion: Defensa y demonstracion del verdadero descubridor de las Quinas del reino de
Santa Fé. Madrid, 1802 (Colmeiro p.69). Compare further, Triana, Etudes, p. 45.

MORE RECENT HISTORY OF THE CINCHONA BARKS. 89

district. From a practical point of view, it was, indeed, important
enough to no longer be compelled to transport the barks around
Cape Horn or over the Isthmus of Panama. This result remains in
its significance uncontended to the favor of Mutis even though
Triana has proved that it was not Mutis himself who first recog-
nized a Cinchona outside of the above-mentioned original Cinchona
region.

The particular circumstances of the personal meeting of Hum-
boldt with Mutis at Santa Fé de Bogota, in the year 1801, were,
indeed, as Triana has shown, of so happy a nature that it may
readily be conceived how Humboldt was led to esteem the Spanish
dilettante higher than posterity, which is more inclined to estimate
the achievements alone, independent of the background of the
station in life of the respective individual.

Humboldt and Bonpland took consideration of the collection of
Mutis, and rendered prominent therefrom the particularly hand-
somely executed colored drawings of the plants of his district.
Humboldt, in a biography," written with warm recognition, dedi-
cates to this man a memorial replete with honor, which even Lin-
nzus has over-estimated, and termed “ phytologorum americanorum
princips.”

In 1777 the Spanish Government appointed Hipolito Ruiz
director of a natural science expedition for the exploration of Peru
and Chili. Ruiz, accompanied by José Pavon and the French —
botanist, Joseph Dombey (p. 47), arrived in 1778, at Lima, and,
after the return of the latter, continued his labors with Pavon. In
1788 they likewise went again to Madrid, where Ruiz, in 1792, as
the first fruit of the expedition, published the Quzno/ogia ; this was
followed, in the years 1798 to 1802, by the Flora peruviana et
chilensis. In Peru and Chili the task of Ruiz and Pavon was
continued by their pupil, Juan Tafalla, who, in turn, was assisted
by Mancilla,? and likewise contributed to the knowledge of the
Cinchonas.

While Mutis did not bring his labors to any conclusion, and the
botanical collection left by him, perhaps not even complete, first

1 Biographie Universelle, Tome XXX, Paris, 1821. The celebrated Plantes égui-
noctiales Humboldt and Bonpland have adorned with a handsome likeness of Mutis.
Regarding Mutis, compare further Triana’s Etudes, and Schumacher’s interesting dis-

uisition, “‘ Linné’s Beziehungen zu New Granada.” Verhandlungen der Gesellschaft
ir Erdkunde zu Berlin, 1880, pp. 98-110. :

2 Compare regarding the above-named Spanish botanists, Colmeiro, La botanica y los

botinicos de la peninsula hispano-lusitana, Madrid, 1858; as also Chiarlone y Mallaina, —

Historia critico-literaria de la Farmacia. Tercera edicion. Madrid, 1875. The latter
name Ruiz more completely, Don Ls spot Ruiz Lopez, He was born in 1754, at
Belerado, in the old Castilian province of Burgos, and died in 1816, at Madrid. Gee

90 CINCHONA BARKS.

arrived at Madrid about the year 1820, and has remained deposited
there,‘ Ruiz published in the Quzxologza, and in 1801, conjointly
with Pavon, ina supplement thereto, the most important results re-
lating to the Cinchonas. The material left by the latter has served
in our day for the foundation of the magnificent work of Howard.
(See section 18, No. 9).

The investigations of these botanists, to which we are indebted for
the first knowledge of most of the Cinchonas, led to a revolution in the
commercial relations of the barks, in that, gradually, about the year
1785, central and southern Peru, as also New Granada, entered
into competition with the district of Loxa, and began to export
barks by way of Callao and the ports located on the Caribbean
Sea.

The selection of the barks which were at that time preferred
was confined to the barks of the branches and twigs, although Con-
damine had himself ascertained in Loxa that originally the strongest,
and thus, presumably, the trunk barks, had been more highly valued.
The greater difficulty of drying experienced with the thick trunk
barks presumably contributed thereto that the collectors directed
their attention more to the bark of the twigs. The Paris druggist,
Pomet, expressly recommended only the “petites écorces fines,
noiratres et chagrinées au dessus, parsemées de quelques mousses
blanches . . . . .” and likewise, in 1724, in the London
market, according to the druggist, Berlu,? the thick, flat trunk barks
were valued much less than the barks of the twigs. After the dis-
covery of the cinchona alkaloids it was shown that the trunk barks,
particularly the flat Calisaya, were usually richer in quinine, so that
these were again more highly prized until, namely, Calisaya
Ledgeriana furnished the proof that also in young barks much
quinine can be formed. |

After the discovery of quinine and cinchonine the botanical and
pharmacognostical investigation of the Cinchonas also received
a new impulse, which was due, e. g., to the labors of Laubert,
Lambert, and particularly in 1826 to Heinrich von Bergen’s
‘Versuch einer Monographie der Chinarinden.” As a drug-
broker in Hamburg, this industrious man, in his work, not only
made application of a practical experience extending through
many years, but also in other considerations placed everything

1 Planchon, Quinguinas, p. 14.
® Histoire générale des Drogues. 1694, p. 133.
* The treasury of drugs unlock'd. London, 1724 (first edition, 1690), “Cortex peruanus,

Jesuits’ bark, China China, Cascarello, Cortex Patrum, from smaller twigs ; that which is
very thick and flat is nothing near so good.” .

MORE RECENT HISTORY OF THE CINCHONA BARKS. 91

together which science could offer regarding this subject; and
especially with regard to the history of the remedy, reference
must also be made to Bergen’s monograph. A valuable supple-
ment consistsin 7 colored plates with admirable figures of Cinchona
rubra, Huanuco, Calisaya flava, Huamalies, Loxa and Jaen; the
descriptions of these barks accomplished all that is possible with-
out the aid of the microscope.

For the application of this latter and most important aid in the
study of the Cinchona barks, and for the first figurative representa-
tions of the anatomical views thereby obtained, we are indebted to
Weddell (died July 22, 1877). The extraordinary significance
of his Histoire Naturelle des Quinguinas, the fruits of extended
travels (1845 and 1848) in Bolivia and Peru, has been everywhere
in the preceding pages sufficiently valued.

How much we are furthermore indebted to the two above fre-
quently mentioned works of Howard and Karsten is manifest from
this entire representation. In the “Flore Columbie terrarumque
adjacentium specimina selecta”’ the latter gives, as the fruits of
observations extending through many years at the place itself,
descriptions and magnificent figures of Cinchona cordifolia, C.
corymbosa, C. lancifolia, and C. tucujensis, as also a number of
species still comprehended by him as Cinchonas, which, at the
present time, are no longer enumerated among the latter, as has
been explained on pages 10, 20 and 51.

The knowledge of the Cinchonas received further enrichment
through the likewise above-mentioned “Quinologie,” for the
publication of which, in 1854, the quinine manufacturer Delondre,
and the chemist and apothecary Bouchardat had associated, after
the former (accidentally), in Weddell’s company, had made a visit
to the forests of Santa Ana, near Cusco. Among the 23 plates of
this Qucnologie are found not only the officinal Cinchona barks,
but in general all those which occurred in the wholesale trade of
that time, together with some false Cinchona barks, very accurately
reproduced; with each bark the yield of alkaloid on a manu-
facturing scale is designated. Phcebus* has dedicated to the barks
of the “ Quinologie” an elaborate microscopical investigation.

The conclusion of so many still open questions regarding the
Cinchonas remains to be hoped for through their forest cultivation,
concerning the development of which the interesting official reports
of the English and Dutch continually afford information. _

It would be very desirable to have a complete systematic knowl-
edge of the entire division of the Cinchonez, and the comparative

1 Die Delondre Bouchardat schen Chinarinden. Giessen 1864, 8°, pp. 74. <:

92 CINCHONA BARKS.

examination of the barks of every individual species from a chemi-
cal and anatomical point of view.

SECTION VIII.

LIST OF THE MORE RECENT PUBLICATIONS RELATING TO THE CINCHONAS
AND THE CINCHONA BARKS.

1. Berg (Otto). Dze Chinarinden der pharmakognostischen Samm-
lung zu Berlin, Berlin, 1865. 48 pagesandtoplates. Quarto.
Price 8 marks (about $2). The plates give transverse sections
of the barks of the following Cinchonas: C. amygdalifolia,
Calisaya, Chahuarguera, Condaminea, cordifolia, heterophylla,
lancifolia, lucumzefolia, macrocalyx, micrantha, microphylla, nitida,
ovata, Palton, Pelletiereana, scrobiculata, succirubra, umbellu-
lifera, Uritusinga. Furthermore, transverse sections of Cinchona
(China) nova surinamensis (from Cascarilla magnifolia, see
page 48), and of the bark of Nauclea Cinchona D. C.

2, Bergen (Heinrich von). Monographie der China. Hamburg,
1826. 4°. 348 pagesand 7 colored plates, with figures of Cin-
chona Calisaya, C. flava, C. Huamalies, C. Huanuco, C. Jaén, C.
Loxa and C. rubra.

3. Bidie. Cinchona culture in British India, being a brief sketch of
ats origin, with practical hints on the chief points connected with
the industry. Madras, 1879. 24 pages, with (not handsome)
figures of Calisaya Ledgeriana and the so-called Cinchona “ pub-
escens”’ (mentioned on page 15).

4. Blue Books. Under the titles of Return, East India, Ginchona
Plant or Cinchona cultivation, are published the official proceed-
ings which relate to the introduction of the Cinchonas into India
and the British colonies.*

The following Blue Books, which are dedicated to this subject
and its further development, have at present appeared (small
folio with maps and wood-cuts ):—

a. Copy of Correspondence relating to the Introduction: of the Cin-
chona plant into India, etc., from March 18 52 to March 1863.
272 pages and 11 maps (Cinchona region in South America, en-

_virons of Lake Titicaca, Province of Caravaya, the Chimborazo).
Contains correspondence of Royle, Markham, Spruce,

Pritchett, Cross, McIvor, Anderson and others.

_ 4. Copy of further Correspondence, etc. April 1863 to April 1866.
_ 379 pages, with two maps of New Granada and Southern India.

1 The Blue Books can be purchased at No. 13 Great Oueen street, Lincoln’s Inn
_ Fields, London, of e 7 Parsee

LITERATURE OF CINCHONA BARKS. 93

Contains monthly reports of the plantations on the Neil-
gherry Hills; annual reports for 1863-64, 1864-65, with details
of method of propagation and cultivation, barking, mossing,
attacks of insects, illustrated by wood-cuts and 4 plates ; report
of Cross’s journey to Pitayo, with map; Cinchona cultivation in
Wynaad, Coorg, the Pulney Hills and Travancore, with map ; in
British Sikkim, the Kangra Valley (Punjab,) the Bombay Presi-
dency and Ceylon.

c. Copy of all Correspondence, etc. April 1866 to April 1870.
285 pages and one map of Southern India,

Contains reports on the Neilgherry and other plantations ;
appointment of Mr. Broughton as analytical chemist, his reports
and analyses ; reports on the relative efficacy of the several cin-
chona alkaloids; on cinchona cultivation at Darjiling and in
British Burmah.

d. Copy of the Cinchona Correspondence. August 1870 to July
1875. 190 pages.

Contains also reports on the manufacture of the alkaloids in
India, collection, shipment and analyses of barks.

The numerous facts derived from the Blue Books in the
present representation of this subject may give an idea of the
richness of their contents.

5. Delondre (Augustin). See Soubeiran et Delondre.

6. Delondre (Augustin Pierre) et Bouchardat (Apollinaire). Quzno-
logie, Paris, 1854, 48 pages and 23 plates. Quarto. Colored
figures of more than 30 different true and false Cinchona barks,
representing their natural appearance very accurately.

7. Gorkom (K. W. van). Die Chinacultur auf Fava. Leipsic,
1869, 61 pages. An account of the management of the Dutch
plantations. Handbook of the Cinchona Culture, translated by
P, D. Jackson, London, 1883; royal 8vo, 292 pages and one

late.

8. pret (Oswald). The researches of this chemist are summar-
ized in the articles Chinarinden, Chinin, Cinchonin, Conchinin, etc.,
in Fehling’s Mewes Handwérterbuch der Chemie, Band Il, 1876 to

1877.

9. ae (John Eliot). Jd/ustrations of the Nueva Quinologia of
Pavon. London, 1862, 163 pages and 30 plates; large folio ;
28 beautifully colored figures of Cinchonas, and two plates
representing the microscopical structure of the barks. Price
126 marks (about 30 dollars). A German edition of the “Nueva

- Quinologia” has been published by the Austrian Pharmaceutical
_ Association. Vienna, 1862, 178 pages, $vo, without the figures

94 CINCHONA BARKS.

(to be had in London at Lovell, Reeves & Co., Henrietta street,

Covent Garden).

10. Howard (J. E.) Qutnology of the East Indian Plantations.
London, one part, 1869; folio; X and 43 pages, with three
plates, representing the microscopical structure of cultivated
Cinchona barks.

Parts Il and III, 1876; folio; XIV and 74 pages, with two (not
very successful) views of Indian Cinchona plantations, and beau-
tiful figures of Calisaya Ledgeriana, Cinchona officinalis, C.
pitayensis Wedd. (C. Triane Karst.), and others. Price of the
three parts 84 marks (about 21 dollars). Compare furthermore
page 63, note 1, and page 87, note 1.
11. Karsten (Hermann). Die medicinischen Chinarinden New

Granadas. Berlin, 1858, 62 pages, 8vo, and two plates, repre-

senting the microscopic structure of transverse sections of Cin-

chona Calisaya, C. lancifolia, C. Uritusinga, Cascarilla (Laden-
bergia) oblongifolia, Cascarilla macrocarpa and others, An

English translation, prepared under the supervision of Mr.

Markham, has been published by the India Office, under the

title of Motes on the Medicinal Cinchona Barks of New Granada,

by H. Karsten, 1861. The plates have not been reproduced,

12. Karsten (Hermann), ore Columbie terrarumgque adjacen-
tium specimina selecta, Berlin, 1858; large folio. The first four
parts of this magnificent work give colored figures of the follow-
ing Cinchonas and allied species, which are likewise designated
by the author as Cinchonas: Cinchona barbacoénsis, C. bogo-
tensis, C. cordifolia, C., corymbosa, C. Henleana, C. lancifolia,
C. macrocarpa, C. macrophylla, C. Moritziana, C. pedunculata,
C. prismatostylis, C. Trianz, C. tucujensis, C. undata,

13. King (George). 4 Manual of Cinchona cultivation in India.
Calcutta, 1876, 80 pages; small folio. Second edition, 1880,
105 pages (out of print).

14. Kuntze (Otto). Gixchona. Arten, Lybriden und Cultur der
Chininbadume. A monographic study based upon personal ob-
servations in the plantations of Java and the Himalaya. Leipsic,
1878, 124 pages, with 3 plates. Compare the review in the
Archiv. der Pharm. 213 (1878) pp. 473-480.

15. Lambert (Aylmer Bourke). 4 description of the genus Cin-
chona, comprehending the various species of vegetables from which
Peruvian and other barks of a similar quality are taken. London,

1797, 4to, 54 pages and 13 plates, in which are figured a speci-
men of Cinchona officinalis sent by Condamine, in 1 740, to Lon-

don, C. pubescens, derived from a plant of Jussieu (see pages

LITERATURE OF CINCHONA BARKS. 95

18 and 19), as also nine other Rubiacez designated as Cinchona.
This publication, pages 30-36, gives also the history of the so-
called China (Cinchona) bicolor, China (Cinchona) Pitoya or
Tecamez, found by the naval physician, D. Brown, in Tecamez, or
Atacamez, on the coast of Ecuador. The origin of this bark,
which is free from alkaloid, and is occasionally mixed with the
American varieties, still remains unknown; it has not the re-
motest resemblance to any Cinchona bark.’

16. Lambert. dx tdlustration of the genus Cinchona, comprising
descriptions of all the officinal Peruvian barks, including several
new species, Baron de Humboldt's Account of the Cinchona Forests
of South America and Laubert’s Memoir on the different species
of Quinguina, etc. London, 1821, 4°.

17. Laubert. Recherches botaniques, chimiques et pharmaceutigues
sur le Quinguina. Fournal de Médecine, chirurgie et de pharm.
mitt, Juillet 1816. An English translation is given in Lam-
bert’s ‘ Illustration,” etc.

18. Maclvor (William Graham). odes on the propagation and
cultivation of the medicinal Cinchonas or Peruvian bark trees.
Madras, 1867. 33 pages and g plates. The second edition,
Madras, 1880, go pages, includes the following publication,
both as unchanged reprints.

19. Maclvor (W. G.). A Jetter on the cultivation of Cinchona
in the Nilgiris, Printed for private circulation only. Ootaca-
mund, 1876. 27 pages. 8°. The principal information con-
tained in both of these publications may also be found in the
Blue Books, further in Gorkom’s publication, see page 93 No. 7.

20. Markham. Zwet Reisen in Peru. A German translation.
Leipsic, 1865.

21. Markham, The Chinchona species of New Granada, containing
the botanical descriptions of the species examined by Drs. Mutis
and Karsten; with some account of those botanists, and of the
results of their labors. London, 1867. 139 pages. The five
plates are reduced, uncolored lithographic copies of the (colored)
figures of the true Cinchonas in Karsten’s work, mentioned on
page 94, No, 12; they represent the following: Cinchona
corymbosa, C. Trianz, C. lancifolia, C. Cordifolia, C. tucujensis.

22. Markham. A Memoir of the Lady Ana de Osorio, Countess of
Chinchon and vice-gueen of Peru (A. D. 1629-1639), with a plea

1 An, indeed, somewhat imperfect figure of the “Tecamez bark” is contained in
Gobel and Kunze, Pharm. Wesabe 1 (1827-1829) Plate XII, Compare further
regarding this bark, Martiny, Rohwaarenkunde | (1843), 387. Vogl, Falsche China-_
vinden 10. Oberlin et Schlagdenhauffen, Fourn. de Pharm. 28 (1878), 252.

96 CINCHONA BARKS.

Jor the correct spelling of the Chinchona genus, by Clements
R. Markham, c.B., F. R.s., commendador da Real Ordem de
Christo, Socius Academiz Czsarez Naturze Curiosorum, cogno-
men Chinchon. London, Triibner & Co., 1874. 99 pages,
4°, with wood-cuts, a map, and 2 heraldic figures in gold print.
Price 28 marks (about $7).

The title of this elegantly executed polemic represents its
purpose, the displacement of the word Cinchona by the diplo-
matically more correct Chinchon (see page 87). The author
gives, furthermore, all the information regarding the Countess
Chinchon, which, through his sagacity, was still capable of being
obtained from her home. Compare, regarding this publication,
the review in Buchner’s Refertorium fiir Pharmacie, XXIV
(1875), 178; also Hanbury, Scéence Papers, 1876, page 475.

23. Markham. Peruvian Bark. A popular account of the intro-
duction of Chinchona cultivation into British India. With maps
and illustrations. London, 1880, 550 pages, three maps, and
three tolerably good illustrations. This book is based upon
those mentioned under Nos. 4, 20 and 21, without presenting
any new results. Price 14 marks [about 3% dollars]. The
principal chapters contained therein are the following: The
knowledge of the bark possessed by the natives of Peru; the
Countess Chinchon ; discovery of the Cinchona trees; descrip-
tion of the same and of their barks; their removal to India;
cultivation of coca (Erythroxylon Coca); Ledger’s merit; ser-
vices of the English travelers, Spruce, Pritchett, Cross, Weir,
Markham; plantations in India, Ceylon, Java, Jamaica and
Mexico ; preparation of the crude alkaloids (‘Febrifuge,” see
p. 80) in India; financial results in India; trees in India; culti-
vation of cotton and of caoutchouc in India.

24. Martius (C. F.Ph. von). Die Fieber-Rinde, der Chinabaum,
sein Vorkommen und seine Cultur. 54 pages. (From Buch-
ner's Neues Repertorium fiir Pharmacie, X\l, 1863, pages 335 to

390).

25. Oudemans (Anthony Cornelis). See page 77.

26. Owen (C. T.). Cinchona Planter’s Manual. Ceylon, 1881.
o03 pages. A guide for the cultivation of the Cinchonas in
ndia. |

27. Planchon (Gustave). Des Quinguinas. Paris et Montpellier,
1864. 150 pages. A good critical review of the Cinchonas

_ and their barks. An English translation has been issued, under

the superintendence of Mr. Markham, by the India Office, under

LITERATURE OF CINCHONA BARKS. 97

the title of Peruvian Barks, by Gustave Planchon, London,
printed by Eyre and Spottiswoode, 1866.

28. Reichardt. Chemische Bestandtheile der Chinarinden. Braun-
schweig, 1855. 164 pages. 8°. 3 plates.

29. Reichel. Chinarinden und deren Bestandthelle. Leipzig, 1856.
56 pages. 8°.

30. Ruiz (Hipolito Ruiz Lopez). Qucnologia, a tratado del érbol
a Quina o Cascarilla, can su descripcion, y la de otras especias de
Quinas unevamente descubiertas en el Pert: ; del modo dé bene fici-
arla, de su eleccion, commercio, virtudes su, Madrid, 1794. 4°.
103 pages.

31. Ruiz. Suplemento 4 la Quinologia. Madrid, 1801. 4°. 154
pages and 1 plate.

32. Soubeiran (J. Léon) et Delondre (Augustin). De 7introduc-
tion et de lacclimatation des Cinchonas dans les Indes néerlandai-
ses et anglaises. Paris, 1868. 165 pages.

33. Triana (José). Nouvelles Etudes sur les Quinguinas d apres les
matériaux préséntés en 1867 & Vexposition universelle de Paris et
accompagnées de fac-simile des dessins de la Quinologie de Mutis,
suiwies de remargues sur la culture des quinguinas—Ouvrage
honoré des encouragements du governement de S. M. Britanique.
Paris, 1870. F. Savy, Folio. 80 pages and 33 plates. Price
70 frances (about $14).

A review of this publication will be found in Just’s Botanischer
Fahresbericht, 1873, page 484.

34. Vogl (August). Chinarinden des Wiener Grosshandels und
der Wiener Sammlungen. Wien, 1867. 8°. 134 pages.

A very exhaustive description (without figures) of the micro-
scopic structure of the barks occurring in the Vienna market, or
preserved in the museums of that city. _ 3

35. Vogl (A.). Bettraége zur Kenntniss der sogenannten falschen
Chinarinden. Wien, 1876. 4°. 24 pages, and figures of 7
microscopic sections. (From a commemorative essay in cele-
bration of the 25th anniversary of the zodlogical botanical
society of Vienna).

The barks, which are here considered and figured, belong on
the one hand to Buena (Cascarilla), Exostemma, Gomphosia,
Nauctea, and Remiia, and on the other to undetermined
mother-plants. Among the latter, ¢. g., Canchona (China alba)
Payta, which contains the alkaloid paytine, (see page 64),
Cinchona (China) bicolorata (page 95), and Cinchona (China) of —

| Truptllo. | , a Re

36. Vij (John Eliza de). <tnologische Studien. 33 essays, re-

98 CINCHONA BARKS.

lating chiefly to the chemical constituents of the barks from
Java and British India. These studies have appeared, since
1866, in Haaxman’s 777dschrift voor Pharmacie in Nederland ;
other publications of De Vrij upon this subject are contained in
the London Pharmaceutical Fournal and in the Paris Yournal de
Pharmacie.

37. Weddell (Hugh Algernon). Afistotre naturelle des Quinguinas,
ou monograple du genre Cinchona, suivie d'une description du
genre Cascarilla et de quelques autres plantes de la méme tribu.
Paris, 1849. 108 pages, 30 plates and 1 map. Folio. Price 60
francs (about $12).

38. Weddell (H. A.). Motes sur les Quinguinas. Extrait des An-
nales des Sciences Naturelles, 5° série, tomes XI et XII. Paris,
Masson et fils, 1870. 8°, 75 pages. A systematic arrange-
ment of the genus Cinchona, and description of its (33) species,
accompanied by useful remarks on their barks. An English
translation has been printed by the India Office, with the title—
Notes on the Quinguinas, by H. A. Weddell, London, 1871, 8°, 64
pages. A German edition by Dr. F. A. Fliickiger has also been
published under the title Uedbersicht der Cinchonen, von H. A.
Weddell, Schaffhausen and Berlin, 1871, 8°, 43 pages, with ad-
ditions and index.

Compare Just’s Botanischer Fahresbericht, 1873, page 4809.

Ld) Boe,

Arariba Bark, 50.

Arariba rubra Martius, 50.
Aribine, 50.

Aricine, 64.

Arrot, 81, 86.

Bado, 83, 84.

Belga, 84.

Bernelot Moens, 27, 33, 34, 97, 68.
Betaquinidine, 63.

Betaquinine, 63.

Bonpland, 89.

Broughton, 27, 34, 68.

Buena, 10, 48, 97.

Caffeic acid from Cinchona cuprea, 53.
Calebeja, 68.
Calisaya, 42, 44.
a Ledgeriana, 17.
Carthagena barks, 45.
Cascadores, 29.
Cascara, 29.
Cascarilla, 10, 98.
e barbacoénsis Karsten, 10, 12, 94.
” Bark, 85.
2) Henleana Karsien, 10, 94.
fs heterocarpa Karsten, 10, 21, 48.
sh magnifolia Eudlicher, 21, 48, 88.
Cascarilleros, 29.
Cascarillos bobos, 11, 23.
= finos, II, 23.
Chifftet, 84.
China (see Cinchona).
Chinasaure, 61.
Chinchon, 83, 87, 95-
Chinchona, 87.
Chinoidine, 64.
. iodosulphate, 77.
Chinova-bitter, 62.
Chinovic acid, 62.
Chinovin, 62.
Chiritmanos, 82.

Cinchamidine, 64.
Cinchocerotin, 59.
Cincholine, 64.
Cinchona, 9, 12, 24, 86.
s alba Payta, 64, 97-
= alkaloids, 63.
" amygdalifolia Weddell, 92.
ee australis Weddell, 22.
. barbacoénsis, 10, 12, 94.
sig Barks, 9.

Cinchona Barks, false, II.

“« white, 35, 64.
bicolor, 95, 97-
—bitter, 62.
bogotensis Karsten, 94.
boliviana, 16, 26.
Bonplandiana Howard, 19.
Calebeja, 68.

ss fibrosa, 44.

aa Ledgeriana, 17.

” Weddell, 16, 25.
Cantagallo, 50.
Caqueta or Caqueza, 45.
Carabaya, 44.
Caroni, 85.
Carthagéne ligneux, 45.
Chahuarguera Pavon, 19.
Chomeliana Weddell, 12.
Columbian, 45.
Condaminea, I9.
cordifolia Mufis, 11, 18, 87, 94,

95-
corymbosa Karsten, 66, 91, 94,

5.
cape Tafalla, 19.
cuprea, II, 50.
Cusco, 44.
flava fibrosa, 44.
flowers, 68.
forests, 25.
fruits, 68.
fusca, 46.

| esd 46.
enleana Karsten, 10, 94.
heterocarpa Karsten, 10, 21,

48.
heterophylla Pavon, II, 92.
hirsuta Ruiz ef Pavon, 12.
Howardiana Kuntze, 13.
Huamalies, D a
Hudanuco, 46, 58, 92.
Jaén, 58, 92.
Josephian: Weddell, 16.
Iaccifolia Mutts, 18,
= Mutis, 18, 25, 44, 66,
lanosa, 1 ee
pine 17, 28, 67, 94

erlana, 17, 20, r, 94.

Loxa, 43, 47, 58,92,
lucumaefolia Pavon, 92.

100 INDEX.

Cinchona macrocalyx Pavon, 92.
- macrocarpa Karsten, 94.

ed macrophylla Karstem, 19, 94.

“ magnifolia, Pavon, 21, 48, 88.

ae micrantha Ruiz ef Pavon, 17,

2.

= sicronhiale Mutts, 92.

- Moritziana Karsten, 94. ~

bis Mutisii Lambert, 12.

ee nitida Ruiz et Pavon, 47, 92.

* nova, 40, 62, 85.

had oblongifolia Mzdts, 48, 88.

" officinalis Hooker, 18, 87, 94.

e ovata Ruiz et Pavon, 92.

. “ y erythroderma, Wed-
dell, 15,

it Pahudiana Howard, 13.

Palton Pavon, 92.

ae Para fusca, 58, 64, 68.
Paraguatan, 49.

pata de gallinazo, 47.
Pavoniana Kunize, 13.

. Pelletiereana Weddell, 92.
peruviana, 44.

pitayensis Weddell, 94. —__

9 Pitoya, 95.

prismatostylis Kars¢en, 19,94.
> pubescens, I5.

. “ Vahl, 12, 16, 58, 66, 87.

purpurescens Weddell, 12.
—tred,

ry le

regia, 42, 44, 48.
oe robusta, 15.
roja, 17, 49, 88.
© rosa, 39, 49.

4: rosea, 49.
eg rubiginosa, 45,
“a rubra, 45, 88, 92.
tt: Santa Ana, 44.
re Savanilla, 49.
ees scrobiculata -Humboldt et
Bonpland, 43, 92-
st succirubra Pavon, 15, 24, 26,
45.
ee Tecamez, 95.
. Tolima, 11, 52.

Triane Karsten, 94, 95-

tucujensis Karsten, Truxillo,

22, 94, 95, 97-

Tuna, Teets 18, 88.

umbellulifera Pavon, 92.

undata Karsten, 94.

Uritusinga Howard, 19.
eee Valparaiso, 49. :
= Weddelliana Kuntze, 13.

Cinchonamine, 54, 64. _

Cinchonamine Bark, 54. _

Cinchonidine, 63, 65.

Cinchonine, 63, 65.

_ Cincho-tannic acid, 60,

_ Cinchotine, 63, 65.

Collahuayas, 82.
Columbian Bark, 45.
Condamine, 18, 24, 81, 86.
Condaminea tinctoria D. C., 49.
Conquinamine, 64.
Conquinine, 63.
Coppicing, 32.
Cortex Araribae, 50.
“ — Cascarillae, 85. -
«“ —_ Cinchone griseus, 46.
- - pallidus, 46.
. = regius, 42.
Cosmibuena, 10, 88.
Crown Bark, 48.
Cuprea Bark, II, 50.
Cuscamidine, 64.
Cuscamine, 64.
Cusco Bark, 44.
Cusconidine, 64.
Cusconine, 64.

De Vrij (see Vrij).
Dombey, 47, 89.

Exostemma, 18, 97.

Febrifuge, 80, 96.
Ferdinandusa chlorantha PoA/, 58.

Gomez, 63.

Gomphosia chlorantha Weddell, 58, 97.
Gorkom, 27, 28, 93.

Grahe’s Reaction, 68.

Hanke, 42.

Hard Bark, 53.
Flasskarl, 25.

Helopeltis Antonii, 29.
Herapathite, 77,79. —
fTesse, 50, 64, 69, etc.
Homocinchonidine, 64.
Homoquinine, 64.
floward, 12, 17,27, 40, 64, 93, 94, ete.
Humboldt, 24, 43, 82, 89.
Hydrocinchonidine, 65.
Hydrocinchonine, 65.
Hydroquinidine, 65.

Jesuits’ Bark, 81, 84, 85, 86, go.
Joosia umbellifera Karsten, 10.
Junghuhn, 27.
Jussieu, 86, 94.

| Kronchina, 48,
Kuntze, 13, 14.

Ladenbergia, 10, 20, 48.
Lagaraye, 61.
Lasionema, Io.
Lawson, 27.

Ledger’s Cinchona, 17.
Lignoin, 60.

Lopez Ruiz, 88.

Lugo, 83.

Loxa, 19, 47, 81, 83, 87.

Mac Ivor, 27, 33-
Macrocnemum, I0, 49.
Mancilla, 89.

Mannitan, 62.

Markham, 49, 82, 87, etc.
Moens (see Bernelot).
Mossing process, 33.
Mutis, 18, 48, 88, 89.

Nauclea Cinchona D. C., 92, 97.

Pahud, 25, 27.
Paraguatan Bark, 49.
Paricine, 64.

Pata de gallinazo, 47.
Pavon, 47, 89.
Paytine, 64.

Peruvian Bark, 9, 86.
Phlobaphen, 60.
Phebus, gt.
Pimentelia glomerata Weddell, 10.
Planchon, 54, 96.

Quercite, 61.
Quina, 35, 88.
Quina-quina, 81.
Quinamine, 64.
Quinetum, 81.
Quinidine, 63, 65.
Quinine, 63, 65.
ah sulphate, 57, 65, 79.
Quino-quino, 81.
inoidin, 64. _
Quinovic acid, 62.
Quinovin, 62.
Quinquina, 9.

Quinquina a cinchonamine, 54.

INDEX. 101

Red Cinchona Bark, 15, 45.
Remijia, 10, 20, 29, 97.
e Bergeniana Weddell, 20.
oe cujabensis Weddel, 20.
« densiflora Bentham et Hooker, 20.
rt ferruginea, D. C., 19.
“ firmula Weddell, 20.
" Hilarii D. C., 20.
«“ hispida 77iana, 20.
« ~ macrocnemia Weddell, 20.
is macrophylla, 19,
by paniculata D. C., 20.
« —_ pedunculata 77riana, 20.
r prismatostylis, I9,
td Purdieana Weddell, 20, 21.
ci Riveroana, 21.
“ tenuiflora Bentham, 20.
a Vellozii, 52.
Remijo, 19.
Renquifo, 47.
Resin-ring, 47.
Ruiz, 47, 88, 89, 97-

Santisteban, 88.
Squibb, 70.

Tafalla, 49, 89.

Talbor, 85.

Tecamez Bark, 95.
Thalleioquin, 65.
Tolima Bark, 11, 52.
Triana, 18, 19, 20, 54.
Tuna, Tunita, 18, 43, 66.

Uprooting, 33-

Vega, 83.
Velloso, II, I9.

Vrij, de, 27, 62, 66, 67, 74, 77, 80, 97, etc.

Weddell, 12, 16, 20, 29, 37, 42, 91, etc.
Wellcome, 19, 29,30

Yungas, 32.

CORRIGENDA.

Page 48, 2d and 4th line from top, vead Crown for Brown.
Page 50, foot-note 1; read Aribine for Arabine.

EXPLANATION OF THE PLATES.

I. Cinchona succirubra, After specimens grown by Mac Ivor, in 1875,
in Ootacamund.

Il. Cinchona Calisaya, Var. Ledgeriana. After specimens from Java.
a, longitudinal section of a flower. 4, Jongitudinal section of a
flower with a short style (the so-called male form, macho of the
Spanish). c, longitudinal section of a flower with a long style (the
so-called female form, Hembra).

Ill. Cinchona Calisaya, Var. Ledgeriana. After specimens from Java.
Representing the magnified capsule of a form provided with hairy
fruits, and seed magnified ten-fold,

IV. Cinchona lancifolia. After specimens from Java, with the use of
plates XI and XII in Karsten’s Mor. Columb. specim. select.

V. Cinchona officinalis. A flowering branch from Darjeeling. Cascarila
heterocarpa (magnifolia). After Karsten’s Flor, Columb. specim.
_ sel, plate VI. Representing the capsules, dehiscing from the
apex.
VI. Remijia pedunculata, (Cinchona pedunculata) from Karsten’s Flor.
Columb. spec. sel. Tab. XXVI.

VII. A. Cinchona Calisaya, transverse section of a young bark. B. Cin-
chona Calisaya, transverse section of an older bark. C. Cinchona
lancifolia, transverse section of the bark. ¢, cork; 4, sclerenchyma
euoggrrer 0, outer bark; J, lacticiferous ducts; g, bast rays
bast wedges); 7, medullary rays; s, bast fibres (bast tubes); %,
staff-shaped sclerotic cells (staff fibres); v, bast. In the lower
figures, sr represents bast fibres of Cizchona cuprea; sc, bast fibres
of Cafisaya and other “true” Cinchona barks, .

VIII. Cinchona cuprea. A highly magnified transverse section. ¢, older;
J, younger cork; 4, sclerenchyma (stone cells); 0, outer bark; 2,
lacticiferous ducts; 7, medullary rays; s, bast fibres (bast tubes);
v, bast; x, crystal ducts.

Cinchona succirubra.

II.

Cinchona Calisaya, Var. Ledgeriana.

Il.

Cinchona Calisaya, Var. Ledgeriana.

IV.

lancifolia.

Cinchona

Cinchona officinalis

Cascarilla heterocarpa (magnifolia )

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Remijia pedunculata.

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