Chapter 52

126Manufacturers are warned by the Department of Agriculture, through the Bureau of Chemistry, that combinations claiming to contain digestive enzymes must be active when sold. If preparations tend to deteriorate in a short time, each lot should be dated and not sold after the period when they become inactive. While every manufacturer must be considered innocent until proved guilty, and ignorant until proved knowing, it is a matter of knowledge that manufacturers have marketed their various digestive mixtures with full appreciation of their worthlessness.—(Jour. A. M. A., Dec. 19, 1914, p. 2234.)

127See report,The Journal, Sept. 9, 1916, p. 827.

128The E. L. Patch Company declares that “no hexamethylenamine has ever been used in the manufacture of Formitol tablets,” and that ammonium chloride and paraformaldehyde are among the ingredients used in the manufacture of these tablets. The hexamethylenamine present in the tablets, therefore, must have been produced by interaction of the paraformaldehyde and ammonium chloride. This does not alter the laboratory findings regarding the composition of the tablets, namely, that they “contain formaldehyde (or paraformaldehyde), an ammonium compound and some hexamethylenamine.”

129After publication of the foregoing report had been authorized by the Council, a letter was received from Charles L. Heffner, advising that the distribution of the circulars has been discontinued.

130The Comparative Values of Some Local Anesthetics by H. C. Hamilton, Detroit, Mich., from the Research Laboratory of Parke, Davis & Co., J. Lab. & Clin. M.4:60 (Nov.) 1918.

131Comparative Efficiency of Local Anesthetics, V, by T. Sollmann, from the Pharmacological Laboratory of the School of Medicine, Western Reserve University, J. Pharmacol. & Exper. Therap.11:69 (Feb.) 1918.

132A Further Contribution to the Pharmacology of the Local Anesthetics by Eggleston and Hatcher, from the Department of Pharmacology, Cornell University Medical College, New York City, J. Pharmacol. & Exper. Therap.13:433 (Aug.) 1919.

133It is well known that when a solution of mercuric chlorid in water is evaporated, mercuric chlorid passes off with the water vapors, but under any condition the amount is but a fraction of the whole. As in Platt’s Chlorides other metallic chlorids are present, the formation of complex mercuric compounds which is bound to have occurred, should retard or prevent the volatilization of mercuric chlorid. That this actually occurs was confirmed by the following experiment: When 1 gm. mercuric chlorid was dissolved in 1 liter of water and the solution distilled, the distillate contained a very small amount of mercury. Then the experiment was repeated after adding sodium chlorid to the solution to simulate the conditions in Platt’s Chlorides. In this case no mercury was found in the distillate. Even were all the mercury in a bottle of Platt’s Chlorides volatilized in a room 10 by 12 by 9 feet, this would be equivalent to only about1⁄500grain mercuric chlorid per cubic foot.

134Iron Citrate Green,The Journal A. M. A., Jan. 12, 1917, p. 135; Reports Council Pharm. and Chem., 1916, p. 42.

135Glycerophosphates,The Journal A. M. A., Sept. 30, 1916, p. 1033; Reports Council Pharm. and Chem., 1916, p. 32. Sodium glycerophosphates. Reports Council Pharm. and Chem., 1916, p. 52.

136Barker and Rowntree (Bull. Johns Hopkins Hospital29:215, 221 [Oct.] 1918) obtained the following results with eucalyptus oil:Cat, hypodermic; survived 3 c.c. per kg.; killed by 5.5 c.c. per kg.Cat, intraperitoneal; killed by 5 c.c. per kg.Dog, hypodermic; survived 1.3 c.c. per kg.They quote from Browning that the following doses, c.c. per kilogram, are not fatal: frogs, 0.5; rabbits, 1 to 5; guinea-pigs, 1.

136Barker and Rowntree (Bull. Johns Hopkins Hospital29:215, 221 [Oct.] 1918) obtained the following results with eucalyptus oil:

Cat, hypodermic; survived 3 c.c. per kg.; killed by 5.5 c.c. per kg.

Cat, intraperitoneal; killed by 5 c.c. per kg.

Dog, hypodermic; survived 1.3 c.c. per kg.

They quote from Browning that the following doses, c.c. per kilogram, are not fatal: frogs, 0.5; rabbits, 1 to 5; guinea-pigs, 1.

137An ampoule labeled as follows: “Coagulen-Ciba, 20 c.c. in sterile solution ready for use. To be shaken. Importé de Suisse. Op. No. 968” was found to measure only 15 c.c. Another ampoule with the same label and Op. No. 9641 contained considerable sediment.

138Since the report was sent to the manufacturers, the results have been published. Hanzlik, P. J., and Weidenthal, C. M., Plasma and Blood Clotting Efficiency of Thromboplastic Agents in Vitro and their Stability, J. Pharmacol. and Exper. Therap.14:157 (October) 1919; Hanzlik, P. J., Karsner, H. T., and Fetterman, J., Anaphylactoid Conditions, J. Pharmacol. and Exper. Therap.14:189 (Oct.) 1919; Hanzlik, P. J., Karsner, H. T., and Fetterman, F., Anaphylactoid Phenomena from Thromboplastic Agents, J. Pharmacol. and Exper. Therap.14:229 (Nov.) 1919.

139La Coste: Annalen der Chemie (Liebig’s)208:34.

140Castelli, G.: Arch. f. Schiffs- u. Tropen-Hyg.16:605, 1912.

141Nichols, H. J.: Salvarsan and Sodium Cacodylate, J. A. M. A.56:492 (Feb. 18) 1911.

142Cole, H. N.: A Study of Sodium Cacodylate in the Treatment of Syphilis, J. A. M. A.67:2012 (Dec. 30) 1916.

143Voegtlin, Carl, and Smith, H. W.: J. Pharmacol. and Exper. Therap.16:449, 1921.

144Wright, B. L.; Kennell, L. A., and Hussey, L. M.: M. Rec.97:607 (April 10) 1920.

145J. A. M. A. June 12, 1920, p. 1654.

146Nichols, H. J.: The Spirocheticidal Value of Disodium Ethyl Arsenate (Mon-Arsone), J. A. M. A.76:1335 (May 14) 1921.

[G]Read before the Section on Pharmacology and Therapeutics at the Sixty-Seventh Annual Session of the American Medical Association, Detroit, June, 1916.

147Lyons, A. B.: Detroit Lancet, 1882, 6, 157.

148The JournalA. M. A., Nov. 21, 1914, p. 1871.

149Zinc permanganate, J. A. M. A., Feb. 6, 1909, p. 488; Reports Chem. Lab.2:15, 1909.

150The Unreliability of Unimportant Medicaments,The JournalA. M. A., Sept. 28, 1912, p. 1156.

151Levy, R. L., and Rowntree, L. G.: On the Toxicity of Various Commercial Preparations of Emetin Hydrochlorid, Arch. Int. Med., March, 1916, p. 420.

152The JournalA. M. A., March 5, 1910, p. 806.

153The JournalA. M. A., Aug. 19, 1911, p. 671.

154The JournalA. M. A., April 20, 1912, p. 1216.

155The JournalA. M. A., April 27, 1912, p. 1298.

156The JournalA. M. A., April 4, 1914, p. 1109.

157The JournalA. M. A., Nov. 27, 1915, p. 1932.

158Reports A. M. A. Chemical Laboratory, 1912, v, 102.

159Am. Jour. Pharm., 1915, 87, 439.

160The JournalA. M. A., Jan. 23, 1909, p. 311.

161The JournalA. M. A., Dec. 31, 1910, pp. 2303 and 2314.

162The JournalA. M. A., Oct. 5, 1912, p. 1295.

163The JournalA. M. A., April 17, 1915, p. 1344.

164The JournalA. M. A., April 4, 1914, p. 1108.

[H]Contribution from the Chemical Laboratory of the American Medical Association.

165The Outlook, Jan. 17, 1917, p. 100.

166Med. Rec., New York, Jan. 27, 1917, p. 160.

167Matas, Rudolph: Burns Treated with Paraffin Mixtures, New Orleans Med. and Surg. Jour., April, 1917, p. 681.

168These determinations will be described later.

169When the sample was first obtained, this feature was not observed.

170Made by the Abbott Laboratories, Chicago, and accepted by the Council on Pharmacy and Chemistry for New and Nonofficial Remedies,The Journal, May 12, 1917, p. 1406.

171No chemical examination was made.

172Sollmann, Torald: Suggested Formulas for Paraffin Films,The JournalA. M. A., April 7, 1917, p. 1037.

173Hull, A. J.: The Treatment of Burns by Paraffin, Brit Med. Jour., Jan. 13, 1917, p. 37; The Treatment of Burns by Paraffin, Therapeutics,The JournalA. M. A., Feb. 3, 1917, p. 373.

174The “soft paraffin” of the British Pharmacopeia resembles petrolatum, U. S. P., Queries and Minor Notes,The JournalA. M. A., April 28, 1917, p. 1281.

175The paraffin used in this formula was supplied by the Standard Oil Company of Indiana; the melting point given by the manufacturers is from 120 to 122 F., which, according to the American Standard of taking melting points, gives higher results than the method described in the pharmacopeia.

176The “Asphalt Varnish” used was obtained from Remien & Kuhnert Company, Chicago.

177While needless, a color resembling “Ambrine” may be obtained by the addition of coloring agents.

178In a personal communication Dr. Sollmann expressed the opinion that the synthetic preparation is inferior to the paraffin used in the formula, basing the view on the greater plasticity of the paraffin. For practical purposes, the paraffin will most probably serve as well as the mixture, especially when it is held in place by bandages, but I believe that the mixture is more adhesive.

179Paraffin is sometimes spoken of as “white wax.” This is unfortunate, as “white wax” is an official name for “White Beeswax, U. S. P.” The term “white wax” is also often applied to “Chinese wax,” which is formed from an insect living on the tree Ligustrum lucidum.

180I am indebted to Dr. Torald Sollmann for these methods.

181When painting a surface with a paraffin film, I found that the temperature of the paraffin should not be too close to the melting point, but several degrees above; otherwise it does not “set” well.

182Fisher, H. E.: Nonadhering Surgical Gauze,The Journal A. M. A., March 25, 1916, p. 939.

183Sollmann, Torald: Paraffin-Covered Bandages,The Journal A. M. A., April 21, 1917, p. 1178.

184Rep. Chem. Lab., A. M. A., 1915, 8, 89.

185Rep. Chem. Lab., A. M. A., 1915, 8, 106.

186Rep. Chem. Lab., A. M. A., 1916, 9, 118.

187U. S. Disp., ed. 19, p. 1315.

188Am. Disp., ed. 2, p. 2022.

189U. S. Pharmacopeia, IX, p. 481.

190Rep. Mass. Bd. Health, 1909, 41, 477.

191Pharm. Jour., 1912, 89, 610.

192Pharm. Jour., 1912, 89, 610.

193The time required to complete the process after the initial portion of lard has been added should be about twenty minutes.

194In order to facilitate the incorporation of the iodine with the fatty base the iodine was first powdered by trituration with alcohol and drying the powder in the air.

195Rep. Chem. Lab., A. M. A., 1916, 9, 118.

196Pharm. Jour., 1912, 89, 610.

197The resultant fatty residue was of a brownish-green color. It no longer had either the taste, color or odor of lard. It was noted that the fats, after removal by this method from the freshly prepared ointment, were nearly white. As the ointment aged the fat became successively darker in color.

198The method depends upon the conversion of all of the iodine compounds into iodate by fusion with sodium hydroxide and oxidation with potassium nitrate. The melt is dissolved in water, a little sodium bisulphite added, the solution cooled and neutralized with phosphoric acid, using methyl orange as indicator. An excess of bromine water is added, and the mixture boiled to expel carbon dioxid and bromine. A little sodium salicylate is added, the solution cooled, an excess of potassium iodid added, and the liberated iodine titrated with tenth-normal sodium thiosulphate in the usual way. One sixth of the iodine found is obtained from the material assayed, the balance being furnished by the potassium iodide added.—Jour. Biochem., 1914, 19, 251.

199In order to determine whether the iodine which is in combination with fat is absorbed through the skin, a few experiments were carried out. The dark-colored iodine-containing fat (obtained from the ointment and washed free from potassium iodide by the method described above) was rubbed thoroughly into the skin of the forearm. It was allowed to remain for four hours, after which the limb was scoured with soap suds. Beginning at the time of the application the urine was collected for forty-eight hours. This was evaporated to small bulk and the residue tested for iodine by Kendall’s method. Small amounts of iodine were found. These findings were taken to indicate that the iodine-containing fat is absorbed to some extent by the skin. It is generally believed that potassium iodide is not absorbed by the unbroken skin. Therefore it seems reasonable to suppose that the principal iodine effects obtainable from iodine ointment are those due to the free iodine contained in the preparation, supplemented to a slight extent by the iodine which is contained in the fatty ointment base.—Jour. Biochem., 1914, 19, 251.

200Unfortunately, the nondescriptive name “aspirin” has been used extensively in European literature and has even got into European pharmacopeias, instead of the scientific name “acetylsalicylic acid.”

201For reference to older literature see Beilstein, II, 1496 (889).

202“The Melting Temperature of Aspirin and Salicylic Acid Mixtures,”Proc. Assoc. Off. Agr. Chem., 1912; Bureau of Chemistry, Department of Agriculture,Bull.162.

203“Assay of Aspirin,”J. Pharm. Chem., 15 (117), No. 7, 213.

204Similar observations were made by Emery and Wright, who state: “An accurate determination of the melting temperature in this way (the rate of heating was such as to give a rise in temperature of about 1° per minute) is rendered difficult by the fact that ‘aspirin’ decomposes on heating, as evidenced in the depression of the melting temperature of the pure substance of about 1° for every five minutes’ heating just below its melting temperature.”

205Isolated crystals attached to the walls of the melting-point tube, apart from the bulk acetylsalicylic acid, melted at a lower temperature.

206An excess of alcohol destroys or lessens the color when only a very minute amount of salicylic acid is present.

207The control should be made each time as standing in the air changes its tinctorial power.

208The presence of pure acetylsalicylic acid does not seem to affect the iron (Fe+++) salicylic acid coloration. The small amount of acetic acid was added to the sodium salicylate control solution (1) to stimulate an acidity approximating the acidity of the acetylsalicylic acid, and (2) since acetylsalicylic acid gives by hydrolysis both acetic acid and salicylic acid, it was thought advisable to add acetic acid to the standard. If there is any free acetic acid in a sample of acetylsalicylic acid containing salicylic acid (which I believe is generally the case when salicylic acid is present) then it would modify the color given by the same amount of salicylic acid alone. For this reason it was thought to be more comparable to have the standard contain a slight amount of acetic acid.

209This standard is somewhat similar to the one proposed by T. W. Thoburn and Paul J. Hanzlik,J. Biol. Chem., 23, 175.

210Apoth. Ztg., 1915, p. 247;Bull. soc. chem., 17 (1915), 401. “Studies of the decomposition of aspirin determined by titrametric methods and by conductivity measurements indicate that the reaction is exceedingly complex,” T. and H.Chem. Abs., 10, 591.

211“In the Matter of Aspirin. Answer to the warning circular of the Bayer Co. of June 1, 1917,” by Mr. Paul Bakewell, Monsanto Chemical Works.

212U. S. patent number 812,554—the novocain patent—declares that the salt melts at 156 C. Evidently based on this, the German Pharmacopoeia Remedia “Hoechst” and past editions of New and Nonofficial Remedies give this melting point. Two specimens of German made novocain obtained from our files, stated to be manufactured by Farbwerke-Hoechst vorm. Meister, Lucius and Bruening, Hoechst a.M. were found to melt, respectively, between 154 and 155 C. and between 153.5 and 154.5 C. when the melting point was determined according to the directions of the U. S. Pharmacopoeia, 9th revision. The various specimens examined at that time melted between 153 and 155 C. and it was decided to permit this range.

213Annual Reports of the Chem. Lab. of the A. M. A., 1915, p. 89.

214Warren, L. E.: Iodin Ointment, Am. J. Pharm., August, 1917, p. 339.

215Ibid., p. 90.

216Reports A. M. A. Chemical Laboratory, 1915, p. 106; Ibid., 1917, p. 87.

217Ibid., 1917, p. 87.

[I]From the Chemical Laboratory of the American Medical Association.

[J]The first article of this series dealt with the purity of acetylsalicylic acid. Leech, P. N.: Examination of American-Made Acetylsalicylic Acid, J. Indust. & Engin. Chem., April, 1918, p. 288. “What’s in a Name?” ibid., p. 255. Acetylsalicylic Acid, or “What’s in a Name?” Editorial, J. A. M. A.70:1097 (April 13) 1918.

218Stieglitz, Julius: Synthetic Drugs II, J. A. M. A.70:688 (March 9) 1918. Leech, P. N.: The Vindication of the American Chemist; Synthetic Drugs, Chicago Chem. Bull. January, 1918, p. 230.

219The Quality of American-Made Synthetics, J. A. M. A.69:1018 (Sept. 22) 1917.

220This committee is composed of Julius Stieglitz, chairman, professor of chemistry, University of Chicago; W. A. Puckner, secretary of the Council on Pharmacy and Chemistry, American Medical Association, and Moses Gomberg, professor of chemistry, University of Michigan.

221Stieglitz, Julius: Shortage of Synthetic Remedies, J. A. M. A.69:400 (Aug. 4) 1917.

222Foreign Patents to Be Open to American Manufacturers, J. A. M. A.69:1550 (Nov. 3) 1917.

223For an interesting discussion, see Stieglitz, Julius: Synthetic Drugs, J. A. M. A.70: 536 (Feb. 23); 688 (March 9); 923 (March 30) 1918. Bracken, L. L.: Federal Trade Commission Requests Use of Official Names, ibid.70:558 (Feb. 23) 1918.

224The testing and standardizing of arsphenamin is being done by the Hygienic Laboratory, U. S. Public Health Service. For chemical tests see reprint 472, Public Health Reports. For a review of the patent literature see article by H. F. Lewis, J. Indust. Engin. Chem., Feb. 1, 1919, p. 141.

225New and Nonofficial Remedies, 1919, published by The Council on Pharmacy and Chemistry of the American Medical Association, p. 82.

226The pharmaceutic monograph on barbital has been omitted. It was published in the 1918 edition of the Annual Reports of the Chemical Laboratory of the American Medical Association.

227New and Nonofficial Remedies, 1918, p. 96.

228Puckner, W. A., and Hilpert, W. S.: Veronal-Sodium and Medinal, J. A. M. A.52:311 (Jan. 23) 1909; Rep. A. M. A. Chemical Lab.,2:13.

229Since this was written, the Council on Pharmacy and Chemistry has also accepted “Barbital-Sodium Abbott.”

230No short, scientific name has been given for this substance although several are under consideration.

231Certain chemical tests are described by E. H. Rankin, Indian J. M. Res.4:237, 1916; also Chem. Abst.10:524. Other references are Schmidt: Pharmazeutische Chemie2:990, Beilstein II, (403). Arends, G.: Neue Arzneimittel und pharmazeutische Spezialitäten, Ed. 4, 1913, p. 271.

232Kennert: Chem. Zentralbl.2:556, 1897.

233Doebner and Gieseke: Ann. d. Chem. (Liebigs)240:291, 1887.

234The validity of this patent is to be doubted.

235Attempts were made to make salts of phenylcinchoninic acid with metals such as copper, mercury, barium and calcium, and also the chloroplatinic acid or periodid addition products. Reliable quantitative results could not be obtained.

236This corresponds to “diluted alcohol, U. S. P.”

237The ethyl acetate was Merck’s product (redistilled), stated to contain 81.6 per cent. of ethyl acetate, 10 per cent. alcohol and alcohol derivatives.

238Seidell, A.: Bull. 67, Hyg. Lab., U. S. P. H. S., p. 11.

239Very recently the Chemical Foundation, Inc., has undertaken to grant licenses for cinchophen. The Calco Chemical Company has obtained one.

240The monograph appears in New and Nonofficial Remedies, 1919.

241The report of these and subsequent toxicity experiments on procain appeared in the report of the Council on Pharmacy and Chemistry, J. A. M. A.72:136 (Jan. 11) 1919.

242Seidell: J. Biol. Chem.14:19, 1913.

243Proposed Institute for Drug Research, editorial Chicago Chem. Bull., April, 1919, p. 67.

[K]See also ????.

244Former estimates of the number of physicians who prescribed Anasarcin appear to have been too high, possibly based on the ratio obtaining in Winchester, Tenn. Inquiry at five fairly busy drug stores in a large eastern city showed that in no instance was the pharmacist even acquainted with the name. One pretended to be, and manifested pity for the inquirer’s ignorance in supposing that it could be imported during the war! He was obviously merely less honest than the others, who frankly admitted they had never heard of it.

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