Cinchona officinalis L (Peruvian bark), Rubiaceae ... - AaronsWorld

Cinchona officinalis L (Peruvian bark), Rubiaceae
and related species
Eric Yarnell, ND
Bastyr University, Department of Botanical Medicine
c­2007
This work may be copied and distributed for any non-commercial purpose as long as it is not
altered in any way.
Contents
1 Highlights 1
2 Basic Clinical Information 2
3 Botanical Information 7
4 Advanced Clinical Information 8
5 Other Viewpoints 10
6 References 14
7 Contributors 15
1 Highlights
Peruvian bark is one of the most important herbal medicines in the history of the world.
Quinine, an alkaloid found in Peruvian bark, was one of the first pharmaceutical drugs, used to treat
malaria patients.
Peruvian bark contains multiple alkaloids that are active against malaria and other parasites.
Peruvian bark is a bitter digestive stimulant.
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Figure 1: One of the original samples of C. succirubra bark sent back to England in 1861 by Richard
Spruce for the Royal Kew Botanical Gardens, one of the first Europeans to successfully steal cinchona
from its native habitat. His samples were ultimately the source of British plantations in India.
Peruvian bark in usual doses is without adverse effects. Excessive doses cause cinchonism.
2 Basic Clinical Information
2.1 Part Used
Dried bark
2.2 Taste
Extremely bitter
2.3 Principal Actions
¯ Antiparasitic
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¯ Antimicrobial
¯ Bitter digestive stimulant
2.4 Major Organ System Affinities
Gastrointestinal tract
2.5 Major Indications
¯ Dyspepsia
¯ Malaria, treatment of, all types
¯ Gastrointestinal parasitic infections
Cinchona, its total alkaloids, and quinine are all useful for rapid destruction of the blood form
(schizont) of malaria, which leads to rapid reduction in fever. Quinine was historically used to prevent
malaria, but it is not the most effective agent for this. Quinine or cinchona alone are not sufficient to
completely eradicate malaria from someone’s body.
Numerous clinical trials have demonstrated that a combination of three or four cinchona alkaloids
is either equally or more effective than quinine by itself for malaria (Borris and Schaeffer 1992; Bunnag,
et al. 1989). Quinine and other alkaloids in cinchona are effective against the asexual blood form
(schizonts) of all four human malaria parasites (P. falciparum, P. malariae, P. ovale,andP. vivax), and
thus can be used to treat infection with any of these. Presently it is reserved for treatment of patients
with drug-resistant falciparum, cerebral malaria. It is also effective against the gametocyte forms of P.
malariae and P. vivax. It is unclear if cinchona or quinine are effective at preventing malaria–they are
historically reported to have some efficacy in this regard but they do not appear to kill sporozoites
(malaria forms injected by mosquitoes) in vitro.
Cinchona and its alkaloids have shown other antibacterial effects, notably in a recent trial by inhibiting
Salmonella typhimurium and Shigella flexneri from invading human colonic epithelial cells (Wolf,
et al. 2005). A similar anti-invasion property was observed with pathogens such as Staphylococcus aureus
and Enterobacter agglomerans (Wolf, et al. 2006). Quinine sulfate has anti-HSV-1 cell invasion and
multiplications effects in vitro (Wolf, et al. 2003).
2.6 Major Constituents
Quinoline alkaloids
2.7 Energetics
2.8 Preparations and Dose
Tincture: 1:3-1:5, 45% ethanol, assuming alkaline menstruum (30% ethanol and 10% vinegar can be
used alternately)
Tincture Doses
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R
HO
H
9
N
Figure 2: Quinine, R = OCH3; Cinchonidine, R = H
R
HO
H
N
9
Figure 3: Quinidine, R = OCH3; Cinchonine, R = H
4
H
H
8
8
N
N
H
H

Acute malaria, adult: 0.5-1 ml (possibly higher) every 2-3 h, adjusted for body size
Chronic GI upset, adult: 0.5-1 ml three times per day in water before meals
Child: as adult but adjusted for body size
Elder: as adult
Decoction: 1 g bark containing 5-6% quinine in 250 ml water simmered for 10 min, yielding approximately
5-6 mg quinine per cup (more if the water is acidic). 1 cup three times per day before meals for
dyspepsia in adults.
Quinine sulfate by mouth for acute, mild malaria: 10 mg/kg body weight every 8 h in adults, usually
combined with 100 mg doxycycline once daily, for 7 d. This dose will usually lead to development
of cinchonism after 2-3 d (the dose threshold for which is approximately 2 g in a day). The dose can
be lowered after 3-4 days, if asexual parasitemia has been eliminated, which will relieve cinchonism
symptoms (Vieira and Midio 2001). Generally this is only used for severe, drug-resistant P. falciparum
infection today.
Totaquine: combination of quinine, quinidine, cinchonine, and cinchonidine, containing 7-20% quinine.
Developed by Health Organisation of the League of Nations as substitute for quinine, introduced
in 1934. Dose 300-600 mg (5-10 grains) three times per day. This does not appear to be available
anymore for unknown reasons.
Quinine dihydrochloride intravenous, for severe malaria: 20 mg/kg body weight in 5% dextrose or
normal saline as a once-only 4 h infusion followed, 4 h later, by quinine dihydrochloride 10 mg/kg
body weight infused over 4 h every 8 h. Generally this is only used for severe P. falciparum infection not
treatable by other drugs. The loading dose should be halved for patients who have received quinine,
quinidine, or mefloquine in the prior 24 h. The maintenance dose should be reduced in patients with
renal impairment.
Quinine can be given intramuscularly at the same dose as for IV, with the doses divided in half and
injected one into each anterior thigh.
2.9 Adverse Effects
¯ Contact dermatitis (principally in workers who made cinchona products)
¯ Nausea, transitory
¯ QT prolongation, torsades de pointes
¯ Hypoglycemia (quinine induces insulin secretion)
QT prolongation is primarily an effect of non-quinine alkaloids, and it can be sufficiently serious
to cause acute ventricular fibrillation and sudden cardiac death. It is not seen with use of whole plant
extracts as a bitter, only with higher doses for attacking malaria.
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2.10 Contraindications
These are largely derived from experience with higher doses of isolated quinine, so they may not be
relevant to the whole herb. But conservativism is required due to the serious nature of the potential
negative results.
¯ Allergy to the herb
¯ Ventricular arrhythmias
¯ Glucose-6-phosphate dehydrogenase deficiency (high risk for hemolysis)
¯ Optic neuritis (may aggravate)
¯ Tinnitus (may aggravate)
¯ History of blackwater fever
¯ Thrombocytopenia purpura
¯ Pregnancy, with great caution (fetal toxicity, primarily auditory nerve damage, may occur)
¯ Lactation (does distribute to breast milk)
¯ Mytasthenia gravis (may aggravate)
¯ Congestive heart failure (negatively inotropic)
2.11 Overdose
Cinchonism
¯ tinnitus
¯ high-tone hearing loss
¯ nausea
¯ dysphoria
Dose threshold: roughly 2 g daily (up to 8 g for many people) of quinine for an average size adult.
Treatment: induce emesis or use gastric lavage. Maintain normal blood pressure and renal function.
Urinary acidification may help with excretion but not if hemoglobinuria is present. Quinine is readily
dialyzable. Hypersensitivity reactions may require epinephrine, corticosteroids, or antihistamines.
Hemolytic-uremic syndrome has been known to occur in patients taking quinine for leg cramps.
This appears to be due to anti-quinine antibodies cross-reacting with red blood cells. Treatment is
by plasmapharesis. Incidence of this complication has not been documented to occur with use of
low-doses of whole herb extracts as a bitter.
Hypersensitivity reactions, manifesting as urticaria, fever, tinnitus, dyspena, asthma, hematuria,
or visual disturbances, are indications for immediate discontinuation of treatment.
2.12 Incompatibilities
Salicylates do not mix with quinine. Tannins will precipitate the alkaloids.
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2.13 Drug Interactions
Quinine and quinindine have numerous drug interactions, of questionable relevance to use of the
whole herb.
Aluminum antacids interfere with quinine absorption. Cimetidine appears to decrease quinine’s
clearance. Rifamycins and terfenadine increase hepatic quinine clearance.
Quinine administered with mefloquine can cause arrhythmias, cardiac arrest, and seizure. There
is also increased risk of arrhythmias in patients taking quinine with amiodarone, cisapride, pimozide,
and halofantrine.
Quinine inhibits vitamin K-dependent clotting factor synthesis enzymes, and thus may have synergistic
anticoagulant effects with warfarin.
Quinine can increase serum concentrations of digoxin.
3 Botanical Information
3.1 Common Names
English Common Names: cinchona, quinine bark, kinakinda, Peruvian bark, Jesuit bark, calisaya
bark, fever tree
Quinine is derived from a Native South American term quina meaning bark.
Cinchona is named after the Spanish Countess Chinchón, wife of viceroy of Peru supposedly cured
from her fever by the bark in 1638.
3.2 Botanical Description
Tropical evergreen trees and shrubs, with large, entire, opposite leaves, stipules, and white or pink
fragrant, actinomorphic, bisexual flowers arranged in cymose inflorescences. The most important
and useful species are Cinchona officinalis, C. calisaya, C. pubescens (also known as C. succirubra), and C.
ledgeriana.
3.3 Interchangeability of Species
Latin name common name Alkaloid content
Cinchona ledgeriana Ledger’s cinchona 5-14%
Cinchona succirubra red cinchona 6-16%
Cinchona calisaya yellow cinchona 3-7%
Cinchona officinalis Jesuit bark 5-8%
3.4 Native Habitat and Current Range
Tropical rainforests of Colombia, Ecuador, Peru, and Bolivia. Medicinal species have also been established
in large plantations in India, Indonesia and the Democratic Republic of the Congo (formerly
Zaire). C. succirubra is an invasive weed in Hawaii and the Galapagos Islands.
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3.5 Ecological Status
Moderately threatened by logging and harvesting for medicine, though medicinal harvesting has been
greatly reduced by availability of cultivated stock.
3.6 Cultivation
Extremely complex and difficult, but now widely established in India, Indonesia and Zaire.
3.7 Wildcrafting
Unclear to what extent this is still practiced due to large-scale cultivated supplies.
4 Advanced Clinical Information
4.1 Additional Actions
¯ Schizontocidal against Plasmodium spp, useful for treatment and suppression.
¯ Anti-ameba (Borris and Schaeffer 1992)
¯ Inhibition of muldrug resistance pump
¯ Negative inotropic
¯ Insulin secratagogue
Cinchona alkaloids act primarily as blood schizonticides. Schizonts are the form of malaria that
exist in red blood cells before giving rise to merozoites, which reinvade red blood cells and split into
sexual forms that penetrate into mosquitoes. Quinine also kills these sexual forms (gametocytes)
for the P. malariae and P. vivax forms. Though quinine and related alkaloids may have some effect
against sporozoites that come out of mosquitoes and actually start a malaria infection, they are not
well-established for preventing malaria, though historical reports suggest they might be protective.
Quinine and related alkaloids do not appear to affect the hynozoites that persist in the liver or any
exoerythrocytic forms of malaria, and thus cannot completely eradicate (cause a so-called radical cure)
malaria on their own in patient infected with P. ovale or P. vivax, which have exoerythrocytic forms.
4.2 Additional Indications
¯ Leg cramps
¯ Babesiosis
¯ Amebiasis
¯ Cancer chemotherapy resistance reversal
Mixed results in controlled clinical trials led to FDA revoking the over-the-counter status for quinine
used to treat leg cramps in 1995 (Man-Son-Hing and Wells 1995).
In a phase I trial, intravenous cinchonine appeared to reverse multidrug resistance in patients with
lymphoproliferative syndromes treated with chemotherapy, but there was concern about potential for
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arrhythmias, as QT prolongation was seen frequently (Solary, et al. 2000). The purported mechanism
of action is inhibition of the MDR pump in cancer cells.
4.3 Constituents
¯ Quinine
¯ Quinidine
¯ Cinchonine
¯ Cinchonidine
4.4 Pharmacokinetics
Quinine is rapidly and about 80% absorbed orally, even in patients with severe diarrhea. It distributes
widely throughout the body. Quinine is 70-80% protein-bound in the blood (this rises above 90% in
patients with cerebral malaria, as well as in children and pregnant women). The elimination half-life
from plasma is 8-21 h in patients with malaria and shorter (7-12 h) in healthy adults. The elimination
half-lives in children are about half those in adults.
All alkaloids in Cinchona undergo hepatic metabolism primarily. Metabolites, mostly hydroxylated
forms, are excreted primarily by the kidneys. Alkaline urine doubles the excretion rate for quinine
compared to alkaline urine.
Quinine does enter breast milk.
4.5 Classic Formulations
King’s American Dispensatory
Tinctura Cinchonae Composita (U. S. P.)—Compound Tincture of Cinchona. SYNONYMS: Compound
tincture of Peruvian bark, Huxham’s tincture of bark.
¯ Red cinchona, 100 g
¯ Bitter orange peel, 80 g
¯ Serpentaria, 20 g
¯ Glycerin, 75 ml
¯ Ethanol 100%, 1,000 ml
¯ Water, 1,000 ml
Mix the glycerin with 850 ml ehtanol and 75 ml water. Mix and powder the herbs (to number 60
fineness). Moisten the powder with 200 ml menstruum and macerate for 24 h in a percolator cone.
Slowly percolate, adding more menstruum mixed in the same proportions as above, until 1,000 ml of
tincture is prepared. Indication: bitter stomachic, 2-3 fluid drams dose.
Related Tinctures.—TINCTURA CINCHONAE COMPOSITA, Compound tincture of Peruvian
bark. The following is the old London formula modified by Prof. King: ”Take of calisaya bark, in
fine powder, 4 ounces; bitter orange peel, 3 ounces; Virginia snakeroot, in moderately fine powder,
6 drachms; saffron, in coarse powder, 2 drachms; cochineal, in fine powder, 1 drachm; good diluted
alcohol, 20 fluid ounces, or a sufficient quantity”(Lond.). Form it into a tincture by maceration or
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percolation, as explained under Tincturae, and make 20 fluid ounces of tincture. This tincture is
generally known as Huxham’s tincture of bark. Prof. King preferred brandy as the menstruum.
TINCTURA ANTIPERIODICA (N. F.), Antiperiodic tincture, Warburg’s tincture.—I. Without
aloes. Rhubarb, thirty-six grammes (36 Gm.) [1 oz. av., 118 grs.]; angelica seed, thirty-six grammes
(36 Gm.) [1 oz. av., 118 grs]; elecampane, eighteen grammes (18 Gm.) [278 grs.]; saffron, eighteen
grammes (18 Gm.) [278 grs.]; fennel, eighteen grammes (18 Gm.) [278 grs.]; gentian, nine grammes
(9 Gm.) [139 grs.]; zedoary root, nine grammes (9 Gm.) [139 grs.]; cubeb, nine grammes (9 Gm.)
[139 grs.]; myrrh, nine grammes (9 Gm.) [139 grs.]; white agaric, nine grammes (9 Gm.) [139 grs.];
camphor, nine grammes (9 Gm.) [139 grs.]; quinine sulphate, one hundred grammes (100 Gm.) [3 ozs.
av., 231 grs.]; diluted alcohol (U. S. P.), a sufficient quantity to make five thousand cubic centimeters
(5000 Cc.) [169 fl, 33]. Reduce the fibrous vegetable drugs to a coarse (No. 20) powder, mix this with
the myrrh and camphor, previously powdered, and digest the whole, during 12 hours, in a suitable,
well-covered vessel, with forty-two hundred and fifty cubic centimeters (4250 Cc.) [143 fl, 140] of diluted
alcohol, on a water-bath, avoiding, as much as possible, any loss of alcohol by evaporation. Then
strain off the liquid with pressure, dissolve the quinine sulphate in the strained liquid, with a gentle
heat, if necessary, filter, and pass enough diluted alcohol, first through the strainer and then through
the filter to make the product measure five thousand cubic centimeters (5000 Cc.) [169 fl, 33]. Each
fluid ounce contains 10 grains of quinine sulphate. Note.—This preparation, made without aloes, is
intended to serve as a stock tincture, from which the regular ’Warburg’s Tincture’ is to be made, when
required. ’Warburg’s Tincture without Aloes’ is also often prescribed or asked for, and in this case the
above preparation is to be dispensed. The original formula directed by Dr. Warburg, contained the
old Confectio Damocratis as one of the ingredients. The latter is a very complex preparation, many
of the constituents being unobtainable at the present day. It has, therefore, been omitted. II. With
aloes.—Extract of aloes (U. S. P.), seventeen and one-half grammes (17.5 Gm.) [270 grs.]; antiperiodic
tincture, without aloes, one thousand cubic centimeters (1000 Cc.) [33 fl, 391]. Dissolve the extract
in the tincture. Note.—When ’Warburg’s Tincture, without any further specification, is ordered, this
preparation (containing aloes) is to be dispensed”—(Nat. Form.).
5 Other Viewpoints
5.1 Discussions in Historical Texts
A Modern Herbal by M. Grieve
Peruvian bark was introduced to Europe in 1640, but the plant producing it was not known to botanists
till 1737; a few years later it was renamed Cinchona after the Countess of Chinchon, who first made the
bark known in Europe for its medicinal qualities. The history of Cinchona and its many vicissitudes
affords a striking illustration of the importance of Government aid in establishing such an industry. It
was known and used by the Jesuits very early in its history, but was first advertized for sale in England
by James Thompson in 1658, and was made official in the London Pharmacopoeia of 1677.
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A Manual of Organic Materia Medica and Pharmacognosy.
by Lucius E. Sayre, B.S. Ph. M., 1917.
532. Cinchona.Cinchona
Peruvian Bark
The dried bark of Cincho’na Ledgeriana Moens (more), Cincho’na calisa’ya Weddell (more), Cinchona
officinalis Linn (more), and of hybrids of these with other species of Cinchona, yielding, when assayed,
not less than 6 per cent. of cinchona alkaloids.
SOURCE VARIETIES, HISTORY, ETC.The genus Cinchona is composed of over three dozen
species, but few furnish the commercial barks. It is well known that the original source of the drug
is South America (10 N. lat. to 19 S. lat., from about 3000 to 12,000 feet above sealevel), the area of
the growth of the various species being confined exclusively to the Andes, chiefly on the eastern face
of the Cordillerasoccasionally on the western face, which is covered by forests. The best known varieties
from South America were the dark brown Loxa bark and the pale yellow-gray Huanuco. The
cinchonas seldom form an entire forest, but rather groups interspersed among treeferns, gigantic
climbers, bamboos, etc., sometimes growing separately in exposed situations, but under peculiar climatic
conditions, such as a great humidity of atmosphere and a mean temperature of about 62. Shade
seems to favor the development of alkaloids. Dymock calls attention to the fact that ”the north or
shaded side of a tree has a richer bark than that on the south side,” a fact which explains the success
of the ”mossing system.” (There are four methods of collecting or harvesting the bark: (1) By taking it
in longitudinal strips from the standing tree and leaving the bark to renew over the exposed wood; (2)
by scraping and shaving off the bark; (3) by coppicing; and (4) by uprooting. The first is most in use . .
. The trees are barked preferably in the rainy season, when the bark ”lifts” or is more easily removed
from the wood. The coolie inserts the point of a knife in the tree as far as he can reach and draws it
down, making an incision in the bark straight to the ground; he then makes another cut parallel to
the first, about an inch and a half distant and, loosening the bark with the back of the knife, the strip
or ribbon is taken off. If the operation is performed carefully and the cambium cells are not broken,
a new layer of bark will be formed in place of that which is taken away. The tree is then covered with
moss, grass, or leaves, bound on by strings of fiber. All this is done to foster the growth of the new
bark (renewed bark) from the cambium and to thicken the untouched layers of natural bark, which is
now termed mossed bark.Pharmacographia Indica.)
Cultivated trees in recent years have been the chief source of the commercial barks. To some
extent the cultivation has been carried on in South America, but great success has attended the persevering
efforts of the Dutch Government and the Government of British India. Extensive plantations
of cinchona are now flourishing, to the extent of several million trees of the more important species,
on the Neilgherry Hills and in the valleys of the Himalaya in British Sikkin. The tree is also cultivated
in Ceylon, Java, Jamaica (Blue Mountains), and other countries.
VARIETIES.There are about twenty varieties of cinchona barks, and it is a very difficult matter to
distinguish them, since they have been and are now changed so much by grafting and crossing. The
varieties generally used and best known are: C. succirubra Pavon, C. calisaya Weddell, C. ledgeriana
Moens, C. lancifolia Mutis (more), and C. officinalis Hooker.
The success of the Dutch planters of Java has been so pronounced that the greater portion of
cinchona bark comes from this place, leading varieties being ledgeriana and succirubra bark. In Java
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great care is exercised in the cultivation. The trees are allowed to reach the age of twelve years before
the bark is collected. The cultivation is largely confined to the variety Ledgeriana. Over 500,000
pounds are collected annually from Java plantations.
DESCRIPTION.In quills or curved pieces of variable size, usually 2 or 3, sometimes 5 mm. thick;
externally gray, rarely brownish-gray, with numerous intersecting transverse and longitudinal fissures,
having nearly vertical sides; the outer bark may be wanting, the color externally being then cinnamon
brown; the inner surface light cinnamon brown, finely striate; fracture of the outer bark short and
granular, of the inner finely splintery; powder light brown or yellowish-brown; odor slight, aromatic;
taste bitter and somewhat astringent.
MICROSCOPICAL.The calisaya (variety Micrantha) transversely shows milk-vessels in the cortical
parenchyma and absence of stone cells, which are present in Lancifolia. The rays of the woody
portion are more elongated and the medullary rays larger in size. Bast fibers comparatively small and
less numerous, but are spindle-shaped, as they are in all true cinchona barks showing longitudinal
section. In C. rubra the stone cells and milk-ducts are both wanting, while the bast fibers are more
numerous and stouter. The bark is richer in coloring matter. In cuprea bark the cork cells are thicker
and the cortical parenchyma cells smaller, stone cells present, milk-ducts absent, few bast fibers, but
the woody portion contains indurated cells, which simulate them. The ligneous cells are very numerous
and extend even down into the medulla. They are smaller than the bast fibers of true cinchona
barks, but much more numerous.
These barks are thoroughly saturated with pigments, principally cinchona red, the phlobaphen
of all cinchona barks. Before microscopical examination these pigments must be removed by a weak
alcoholic solution of ammonia. This requires considerable practice (Dohme). Compared with other
barks, the fibers of the liber of cinchona are shorter and more loosely arranged, being for the most
part separated into simple fibers imbedded in the bast parenchyma, or united into very short bundles.
Grahe’s test for the distinction of cinchona bark is as follows: On heating about 0.1 Gm. (1.5 gr.) of
the powdered bark in a dry test-tube a tarry distillate of a red color is obtained.
Powder.Microscopical elements of: See Part iv, Chap. I, B.
OFFICIAL PREPARATIONS.
Fl. Ext. Cinchonae, Dose: 15 drops (1 mil).
Tr. Cinchonae , 1 fl. dr. (4 mils).
532a. CINCHONA RUBRA.The dried bark of Cinchona Succirubra Pavon (more) or its hybrids,
yielding not less than 6 per cent. of the total alkaloids of Cinchona. ”In quills or incurved pieces,
varying in length, and from 2 to 4 or 5 mm (1/12 to 1/6 or 1/5 in.) thick; the outer surface covered
with a grayish-brown cork, more or less rough from warts and longitudinal, warty ridges, and from
few, mostly short and not frequently intersected transverse fissures, having their sides sloping; inner
surface more or less deep reddish-brown and distinctly striate; fracture short, fibrous in the inner layer;
outer layer, granular. For years practically all of the red cinchona bark, so called, was only a hybrid, but
recently, and especially for a year past, fine quill bark of pure succirubra has frequently been received.
Powder.Microscopical elements of: See Part iv, Chap. I, B.
CONSTITUENTS.Upon quinine, C20H24N2O23H2O, the bark almost exclusively depends for its
value. This alkaloid is colorless, amorphous, or in acicular crystals; inodorous, very bitter; soluble in
1670 parts water, 6 parts alcohol, 26 parts ether. Aqueous solutions of the salts have a blue fluorescence,
12

and when treated with chlorine water and ammonia a beautiful green color is produced”Thalleoquin
test.” The solutions deviate the plane of polarization to the left. The tartrate is soluble in water. A
cold aqueous solution of the sulphate remains unaffected by potassium iodide T. S. (difference from
quinidine). The other prominent principles are:
CINCHONIDINE, C19H22N2Oisomeric with cinchonine, non-fluorescent; forms colorless, anhydrous
crystals, soluble in 20 parts alcohol (80 per cent.), 1680 of water, and 188 of ether. The sulphate is
more soluble in water than quinine, and the tartrate very insoluble. The Thalleoquin test (see above)
gives a white precipitate. Represented in Cinchonidinae Sulphas.
CINCHONINE, C20H24N2Owhite lustrous prisms, soluble in 3760 parts water, 116 parts alcohol,
and 526 parts ether; has exactly the opposite action to cinchonidine and quinine upon polarized light.
QUINIDINE, C20H24N2O2isomeric with quinine; crystallizes in prisms soluble in 2000 parts water,
0.8 part alcohol, about 30 parts ether; turns the plane of polarization to the right. A cold aqueous
solution of the sulphate yields a white precipitate with potassium iodide T. S. (difference from sulphate
of quinine). Represented in Quinidinae Sulphas.
Among the unofficial alkaloids and principles found in the bark are the following: Isomeric with
quinine and quinidine is quinicine; with cinchonine and cinchonidine, are cinchonicine, homocinchonine,
homocinchonidine, homocinchonicine, and apoquinamine; a brown amorphous alkaloid is
obtainable from the mother-liquor known as chinoidine (quinoidine), a mixture of various not welldefined
alkaloidal substances; kinic acid, C7H12O6, and kinovic acid, kinovin; bitter cinchonic acid
(derived from preceding); volatile oil, a minute quantity.
Separation of Total Alkaloids.Moisten powdered cinchona with ammonia water and allow it to
stand for an hour, then hot water is added. To the mixture, after cooling, milk of lime is added and
the whole evaporated to dryness. This is placed in an extraction apparatus and exhausted with ether.
Water acidulated with HCl is added to neutralize the alkaloids and the ether distilled off. The cooled
liquid is filtered and decinormal solution of soda is added. Finally, sodium hydrate is added to complete
the precipitation of the alkaloids. There are numerous other processes, but this seems a simple and
satisfactory one to use for assay purposes.
YIELD OF ALKALOID.The richest government bark brought to the market until recently has not
exceeded 91/2 per cent. of sulphate of quinine; 7 to 8 per cent. is a good average in government
plantations. Barks taken from the trees in the government gardens at Pioeng Goenoeg, Java, have
recently been analyzed and found to equal respectively 12.66 and 16.04 per cent. of quinine sulphate.
ACTION AND USES.The action of cinchona bark is due almost entirely to the alkaloids therein
contained. Quinine is a powerful antiseptic, destructive, in weak solution, to infusorial and vegetable
life. Internally it stimulates the muscular fibers of the stomach, acting as a bitter tonic, invigorating
the vital functions and aiding digestion. In large doses the brain is affected, giving rise to symptoms
such as fullness, frontal headache, deafness, ringing in the ears, and mental dullness. This effect is
called ”cinchonism” attributed to partial anaemia of the brain, contraction of blood-vessels, etc. Heart
action is depressed. Reflex excitability of the spinal cord is lowered. In the blood, quinine arrests the
migration of the white corpuscle and checks its amoeboid movement; the oxygen-carrying function
of the red corpuscle is impaired; infectious micro-organisms in the blood and tissues are probably
rendered inactive or destroyed. The toxic symptoms produced by quinine and allied salts are spoken
of collectively as cinchonism, which ordinarily is not allowed to go further than tinnitus aurium.
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Dose of cinchona: 15 to 60 gr. (1 to 4 Gm.), in powder, fluidextract, or its equivalent in the salts of
the alkaloids.
OFFICIAL PREPARATION. Tinctura Cinchonae Compositae (10 per cent., with bitter orangepeel
8 per cent., and serpentaria 2 per cent.) 1 to 4 fl. dr. (4 to 1.5 mils).
5.2 Ethnobotany
(Dr. Kingsbury will complete this section in the future.)
6 References
Borris RP, Schaeffer JM (1992) Antiparasitic agents from plants In: Nigg HN, Seigler D (eds) Phytochemical
Resources for Medicine and Agriculture (NY: Plenum Press): 117-58
Bunnag D, Harinasuta T, Looareesuwan S, et al. (1989) A combination of quinine, quinidine and
cinchonine (LA 40221) in the treatment of chloroquine resistant falciparum malaria in Thailand: Two
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7 Contributors
Primary author: Eric Yarnell, ND
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