The Federal Trade Commission has not issued any licenses for the manufacture of “holocain hydrochlorid.” The John T. Milliken Company has withdrawn its application. The H. A. Metz Laboratories (Successor to Farbwerke Hoechst Company, New York) are making the product in this country.
CINCHOPHEN (PHENYLCINCHONINIC ACID, U. S. P.; ATOPHAN)
Cinchophen (phenylcinchoninic acid) was introduced in the United States as a medicine under the proprietary name “atophan,” by Schering and Glatz, New York City, who before the war were the American agents for the German manufacturers “Chemische Fabric auf Actien von E. Schering, Berlin.” Phenylcinchoninic acid (2 phenyl-quinolin-4 carboxylic acid) was first described by Doebner and Gieseke[233] in 1887, who prepared it by warming together pyro-racemic acid, benzaldehyd and anilin in alcoholic solution; it has the structural formula:
The chief use of phenylcinchoninic acid is as an antiuric acid agent, especially indicated in gout.
In 1913, the German house of Schering was made the assignee of patent 1045759 granted by the United States government[234] for the manufacture of phenylcinchoninic acid: at about the same time the product was admitted to the U. S. Pharmacopeia IX, under very loosely constructed standards.
Some time after the beginning of the European war the proprietary “atophan” became scarce in America. In 1917, however, Schering and Glatz, New York, placed American-made atophan on the market and submitted it to the Council on Pharmacy and Chemistry. Later, other firms began to manufacture the product and also submitted specimens. During the time it was investigating these products, the Federal Trade Commission decided that a license was needed to manufacture phenylcinchoninic acid under the patent just referred to, so that altogether the laboratory had a number of specimens to examine.
In making the examinations for the Council, the laboratory was practically confined, by virtue of the Food and Drugs Law, to limit its requirements of purity to those of the Pharmacopeia. Practically, the only tests were melting point, ash and solubility. According to the U. S. Pharmacopeia the melting point is “about 210.” In New and Nonofficial Remedies, 1918, it was explained that atophan “complies with the standards for phenylcinchoninic acid, U. S. P., but melts between 208 and 212 C.” The U. S. Pharmacopeia requires that no weighable ash remains on incinerating about 0.5 gm. of phenylcinchoninic acid. Considerable variations, especially in melting points, were found, as can be seen from Table 4.