Proprietary Association Meets A STAFF REPORT JL H E chemistry of folic acid, its pharmacology and therapeutic indications, and the production of amino acids for medicinal use, \ve»*e among t h e subjects taken u p for discussion at t h e midyear meeting of the Scientific Section, Proprietary Association of America, i n N e w York City, D e c . 6. The chairman of t h e section, W. L. Sampson of the Merck Institute of Therapeutic Research, presided. Functions of t h e amino acids, the "building blocks of proteins", were described i n the l i g h t of recent knowledge b y Charles F . K a d e , Jr., director of biochemical research, FrederickStearns&Co., Detroit. Factors in the synthesis of proteins were growth, repair and replacement, and the synthesis of antibodies. Second, the synthesis of special products involves hormones, creatinine and other extractives, purines, avnd detoxicants. Third function of t h e amino acids, is t o produce energy. Daily amino acid requirements were placed at from 60 to 70 grams for protein deficiency or malnutrition. T h i s is quite large and means t h a t they cannot b e a d ministered like vitamins in the form of pills or tablets. Oral hydrolyzates for intravenous treatment offered a good source of the essential a m i n o acids. A n intravenous hydrolyzate must b e sterile, nonantigenic, and nonpyrogenic. Other required characteristics were a proportion o f amino acids of value t o human nitrogen metabolism; a k n o w n and a lo*w asli content; an absence of toxic substances, l o w bacterial contamination, and suitable t a s t e . T h e simplest way of preparing a product t o meet required specifications, Dr. K a d e said, would be t o make mixtures of s y n t h e t i c and purified amino acids. T h e c o s t o f purifying or synthesizing sufficient quantities, however, is still very high. Further, there is mounting evidence that proteins contain an unknown factor, perhaps another amino acid, t h e constitution o f which is not known, or a
necessary linkage which cannot b « synthesized b y animals or humans at a rate commensurate w i t h their needs. T h e National Research Council bias reported that the normal individual c*btains daily not less than 1 gram of protesin per kilogram of body weight for adequate maintenance. However, i n sickneass the demand for amino acids m a y be greatly increased, the speaker thought, and since persons malnourished or ill m a y be unable to obtain or absorb sufficient amino acids from food, some readily available supply of amino acids must be furnished. Ourrent amino acid sources are casein, the principal protein of milk, and lactalbumin, also obtained from milk. Casein hydroLyzates have a strong flavor which is extremely difficult to disguise. However, sucb. products are designed chiefly for parenteral administration. Casein is used as an amino acid source because the commercial grades are nearly pure and very low in carbohydrate and ash. Lactalbumin is a protein of better biological value than casein, and is coming into greater use as supplies of low ash content become available. T h e use of other animal proteins of high biological, value such as blood fibrin has been hindered b y a lack of sufficient supply. T h e vegetable proteins, as represented b y the soybean, are usually of lower biological valtae, but may be improved readily b y the addition of pure amino acids. Y e a s t proteims have a distinct disadvantage for medicinal use because of their high purine contentRutin, the drug developed b y crxemists of t h e Department of Agriculture Cor the treatment of capillary fragility, could be used to treat upward of 1,000,000 p-ersons, said W. G. Bywater, research division, S. B . Penick & Co. Requirements were placed at some 3,000,000 20-gram bablets, a quantity equivalent to 48,000 ll>. The drug, soluble in alcohol, isopropyl adcohol, and methanol, i s comparatively ststble to
Speakers at midyear meeting: Charles F. Kade, Jr.', Frederick Stearns & Co.; W9 G. Bywater, S. B. Penick £c Co.; Louis M . Roeg, Merck & Co,; Raymond W. Cun-
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acid hydrolysis and should b e handled conservatively a s far a s heat is concerned. Rutin w a s said to offer drying problems and i t has been found by investigators t o have a short melting range. I t s identification through color tests is difficult. Further, it picks u p metals readily in either acid, alkali, or neutral solutions and reduces ammoniacal solutions. Two papers were read before the scientific section on folic acid. I t s chemistry was discussed b y R. B. Angier, and i t s pharmacology a n d therapeutic indications b y R. Cunningham, both of Lederle Laboratories, Pearl River, N. Y. Dr. Angier explained the folic acid factors, some of which are obtained in crystalline form, including liver L. casei, yeast L. casei, fermentation L. casei, and vitamin B C conjugate. It was shown that the fermentation L. casei factor, through hydrolysis, yields a fluorescent compound and a n aromatic amine. Work w i t h this and other degradation products w a s described. Certain of the compounds a.re difficult to work with as melting points were not known. The fluorescent compound was found t o be a pteridin. Infrared absorption spectra showed a close parallel between the L. casei factor from liver and the synthetic material. Dr. Cunningham, in outlining recent pharmacological work with folic acid, gave the results of intravenous administration of pteroylglutamic acid o n test animals. Death rates were lowest for mice i n these experiments, a n d highest (100%) for guinea pigs. The subject o f oral microorganisms and the incidence of pathogenic and nonpathogenic staphylococci i n the human throat formed t h e basis of a paper read b y George F. Reddish, Lambert Pharmacal Co., St. Louis. Out of a total of 8 6 subjects used i n t h e research, 36 had febrile type sore throats accompanying colds during t h e period November—February. R. L. Conklin, medical and research director, Miles Laboratories, Elkhart, Ind., led a discussion on procedures in setting up a clinical research project, and Louis M . Roeg, Merck & Co., described n e w products in 1946 National Formulary bulletins.
ningham, J^ederle Laboratories; W. L. Sampson, Merck Institute of Therapeutic Research, and chairman of the section; R. B. Angier, Lederle Laboratories
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