Cinchona bark

Alkaloid of cinchona bark used to treat malaria)... 

The success of quinine inspired the search for other antimalarials. The greatest impetus for the development of synthetic dmgs came this century when the two World Wars intermpted the supply of cinchona bark to the combatants. A stmcturally related 4-quinolinemethanol is mefloquine (65, Lariam [51773-92-3]) which now serves as an effective alternative agent for chloroquine-resistant P. falciparum. This is a potent substance that requires less than one-tenth the dose of quinine to effect cures. There are some untoward side effects associated with this dmg such as gastrointestinal upset and dizziness, but they tend to be transient. Mefloquine is not recommended for use by those using beta-blockers, those whose job requires fine coordination and spatial discrimination, or those with a history of epilepsy or psychiatric disorders. A combination of mefloquine with Fansidar (a mixture of pyrimethamine and sulfadoxine) is known as Fansimef but its use is not recommended. Resistance to mefloquine has been reported even though the compound has not been in wide use. 

QuinidJne. Quinidine, an alkaloid obtained from cinchona bark (Sinchona sp.), is the dextrorotatory stereoisomer of quinine [130-95-0] (see Alkaloids). The first use of quinidine for the treatment of atrial fibrillation was reported in 1918 (12). The sulfate, gluconate, and polygalacturonate salts are used in clinical practice. The dmg is given mainly by the oral (po) route, rarely by the intravenous (iv) route of adniinistration. It is the most frequentiy prescribed po antiarrhythmic agent in the United States. The clinical uses of quinidine include suppression of atrial and ventricular extrasystoles and serious ventricular arrhythmias (1 3). 

It is over three centuries since cinchona bark came into use in European medicine, and no other natural drug has had so much written about it. There are the stories, sometimes legendary, of its discovery by Europeans, vigorous early discussions of its therapeutic value, the destruction of the S. American cinchona trees to meet the demand for bark, the labours of botanical explorers in collecting seed for the formation of plantations, the establishment and development of these plantations in Ceylon, India and Java, the competition between them, the gradual emergence of Java as the world s most important source of supply of cinchona bark, and the development of the manufacture of quinine sulphate in Europe, the United States and the Tropics. ... 

The disadvantage in war periods of relying on a single source of supply for an essential commodity became evident when Java was invaded by the Japanese in March 1942, the world being thereby deprived of about 90 per cent, of its customary supply of cinchona bark. Quinine was ther still considered an indispensable drug for the treatment of malaria an<3 its use had to be restricted to that purpose stocks of quinidine wew similarly reserved for use in cardiac disease, In efforts to deal with th<... 

Analyses of Cinchona Barks. For galenical preparations, pharmacopoeia recognition is usually restricted to barks of cultivated cinchona species known to yield total alkaloids satisfactory in composition thus, the British Pharmacopoeia 1932 prescribes the varieties to be used, and specifies not less than 6 per cent, of total alkaloids, of which at least half must be quinine and cinchonidine, determined by the process prescribed. Numerous other processes have been published and references to the more important of these are given under the following headings —identifica-... 

Detection. Cinchonine is sparingly soluble in all ordinary solvents, is not fluorescent in dilute sulphuric acid, is dextrorotatory, forms a soluble tartrate and hydriodide and does not give the thalleioquin reaction. Hesse s homocinchonine has been shown to be impure cinchonine. Cinchonidine, C49H22ON2. This alkaloid occurs in most varieties of cinchona bark, but especially in C. succiruhra. 

A notable change in methods of isolating alkaloids from plant materials has been described by Applezweig, depending on the use of a suitable ion-exchange material and capable of application on a semi-micro scale or for industrial use. It has been applied to the preparation of the total alkaloids of cinchona bark (totaquina) and according to Sussman, Mindler and Wood, is also used industrially for the recovery of hyoscine. 

Mth quinine in cinchona bark), is now prc]5.a> cd fmin anilmc. The aniline, in pioccss of oxidation to quinone, -ippeais to jiass throug h the following intermediate stag es. 

The oldest effective drug for the treatment of this disease is indisputably quinine. Although the antipyretic activity of cinchona bark was known to the Incas, it remained for the Jesuit missionaries to uncover its antimalarial properties in the early seventeenth century. The advance of organic chemistry led to the isolation and identification of the alkaloid, quinine, as the active compound at the turn of this century. The emerging clinical importance of this drug led up to the establishment of cinchona plantations in the Dutch East Indies. This very circum-... 

China-ol, n. baleam of Peru, rindet/. cinchona bark, Peruvian bark. rindensauret /. quinic acid, -rot, n. cinchona red. 

Fieber-pulver, n. fever powder, ague powder (antimonial powder), -rinde, /. cinchona bark. 

Jesuiten-rinde, /. Jesuit bark (cinchona bark), -tee, m. Mexican tea (Chenopodium ambro aioidea). 

By extraction of Cinchona bark with aromatic hydrocarbons, conversion of the crude alkaloids into the sulfates and fractional precipitation with NaOH as sulfate. 

Steere, W. C. 1945a. The Cinchona bark industry in South America. Sci. Monthly 61 114-126. 

Figure 14.15. Structures of some alkaloids from Cinchona bark...

All the material world is formed of mixtures, aggregates or more complex combinations of pure substances. For example, it is well known that the bark of the Cinchona tree Cinchona calisaya) shows a remarkable antimalarial activity, which is due, not to the bark as such, but to some "pure substance" which forms an integral part of it. In 1820, the French pharmacists Pelletier and Caventou isolated the active principle of the Cinchona bark, which they called quinine, as a pure, crystalline substance, m.p. 177 °C (dec), -169°, and assigned an elemental... 

Quinine Sulphate. 90-100 g of cinchona bark is ground up with 250 cc of milk of lime. Evaporate to dryness on water bath, cool, and powder. Shake this powdered residue with 200 cc of chloroform and allow to stand in a flask for 12 hours. Filter and wash with chloroform. 

Cinchona alkaloids [Qninidine (6), Quinine (7)] Cinchona spp. (Cinchona bark) Cardiac antiarrhythmic Antimalarial... 

At the turn of the nineteenth century, methods became available for the isolation of active principles from crude drugs. The development of chemistry made it possible to isolate and synthesize chemically pure compounds that would give reproducible biological results. In 1806, Serturner (1783-1841) isolated the first pure active principle when he purified morphine from the opium poppy. Many other chemically pure active compounds were soon obtained from crude drug preparations, including emetine by Pelletier (1788-1844) from ipecacuanha root quinine by Carentou (1795-1877) from cinchona bark strychnine by Magendie (1783-1855) from nux vomica and, in 1856, cocaine by Wohler (1800-1882) from coca. 

Coenegracht et al. [3] have introduced a four solvent system to compose mobile phases for the separation of the parent alkaloids in different medicinal dry plant materials, like Cinchona bark and Opium. Through the use of mixture designs and response surface modeling an optimal mobile phase was found for each type of plant material. These new mobile phases resulted in equally good or better separations than obtained by the procedures of the Pharmacopeias. Although separations were as predicted, the accuracy of the quantitative predictions needed to be improved. 

Quinine is a natural alkaloid obtained from cinchona bark. 

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