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QUININE (lcvvin'en or 'delft), QUIN INA, or QUINIA, a drug (CoHts/s1202) largely used in the cure of malarial fevers, in which it is regarded as a specific. It is also a valuable tonic. Quinine is one of the five most important of the 21 alkaloids obtained from the bark of the cinchona-tree (Peruvian bark; see BARK, PERUVIAN) ; the others being quinidine, cinchonidine, cinchonine and hydroquinine (q.v.). The curative power of these alkaloids is accurately shown by the report, dated April 1868, of a commission appointed by the British Indian government (Madras) after the sugges tion of Clements R. Markham, C.B., F.R.S. Cases of fever numbering 2,472 were treated, and the result showed failures per 1,000 as fol lows: Quinidine, 6; quinine, 7; cinchonidine, 10; cinchonine, 23. Quinine alkaloid is seldom used, as it is very insoluble (59° F., 1,600 parts water). The salt known as quinine sulphate (C201-IuNt02)HtS0 7H,0, is generally in use but the acid hydrochloride (also called the ((chlorate')) is preferred by careful practitioners; and the tannate for children and the more susceptible, in doses two to three times as large.

The average dose of quinine sulphate for adults in the United States is four to five grains every three or four hours beginning a few hours after a paroxysm and continuing until three hours before another is due, when a much larger dose is given. If, as is to'be expected, no paroxysm occurs, the treatment is renewed for some hours on the second day, and then again on the ninth day, which completes the cure. In warmer and more fever-ridden countries, twice to three times this amount is given. Quinine is also used with great success as a prophylactic. Since 1902 it has been distributed free by the Italian gov ernment in the malarial sections. The preven tive amount for adults is five to seven grains of the sulphate per day divided into two doses. Children receive two to three grains daily during the malarial season. As a tonic the best results are obtained by doses of one-half grain of the hydrochloride twice daily. In the ad ministration of quinine it has been repeatedly noticed that toxic symptoms have been de veloped in some cases; and investigations have shown that in certain conditions both cinchonine and quinine develop poisonous isomeric forms, known as cinchotoxine and quinotoxine. This

change takes place in the preparation of quinine when the heating at 212° is prolonged and acetic acid is present. The same changes have been noted at the temperature of the body in the presence of such acids as are sometimes found in the digestive tract, particularly acetic and citric acids. The poisonous symptoms are sometimes severe, and such patients should be treated with quinidine (q.v.). The average con sumption of quinine sulphate in the world is 15,000,000 ounces a year, and the approximate average net cost of production is 18 cents per ounce. The importations into the United States in the fiscal year ended 30 June 1918 were 3;73,628 pounds of cinchona and other quinine yielding barks, valued at $810,775, and capable of supplying an average of 4 per cent (2,095,122 ounces) of quinine sulphate; and 1,445,702 ounces of quinia sulphate and other alkaloids and salts of cinchona bark, valued at $656,945.

To manufacture quinine, the bark is ground to a No. 70 powder (screens of 70 meshes to the inch), and mixed with one-third its weight of slaked lime, made into a paste with water and dried thoroughly at 212° F. It is then powdered and mixed with petroleum and boiled about five hours, the alkaloids in the bark dis solving in the oil, or amyl alcohol may be used for the solvent. The powder is then al lowed to settle, and the oil is drawn off and agitated with hydrochloric acid. The alkaloids in mixture. known commercially as quinoidine, now leave the oil and go to the acid-water, in which they are more soluble than in the oil. The oil and water separate upon standing, and the acid water is drawn off and neutralized with an excess of ammonia or soda, when the quinine and other alkaloids are precipitated together. The alkaloids are redissolved in very dilute sul phuric acid and then the solution is almost but not quite neutralized by very dilute soda solu tion cautiously added. It is then heated to the boiling point, and enough boiling water added to make 70 ounces of water for each ounce of mixed alkaloids. Upon cooling, crystals of quinine sulphate are thrown out, leaving the other alkaloids in the solution — called the mother-liquor (see QUINIDINE). The quinine is purified by recrystallizing several times from its solution in water at 212°.

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