84 THE SIMPLER NATURAL BASES 



the hydrate theory proved to be untenable, epinephrin was made synonymous with 

 adrenalin. 1 



Preparation and Purification of Natural Adrenaline. 



The various processes depend on the fact that the active principle 

 is extracted from the glands by water, neutral or acidulated, that it 

 is not precipitated from its concentrated aqueous solution by alcohol, 

 nor by neutral lead acetate, and that it separates in a crystalline form 

 from suitably purified and concentrated aqueous solutions on the addi- 

 tion of concentrated ammonia. On account of the readiness with which 

 adrenaline undergoes oxidation various precautions have been sug- 

 gested, such as preventing the access of air by means of a current of 

 hydrogen or of carbon dioxide, and carrying out the final precipitation 

 under a layer of petrol. For the same reason it is very convenient to 

 extract with water containing sulphur dioxide. 



Takamine [1901, 2] extracted the minced gland at 50-80 for five hours with water 

 acidulated with acetic or hydrochloric acid, shaking at intervals. The extract was then 

 raised to 90-95 for one hour to coagulate the proteins, using a layer of fat or current of 

 carbon dioxide to avoid oxidation. The glands were extracted a second time and the mixed 

 extracts were concentrated in vacuo, and then precipitated with 2-3 volumes of alcohol. 

 After filtration, the filtrate was again evaporated to a small bulk and was then precipitated 

 with excess of concentrated ammonia which caused the crude adrenaline to separate in 

 sphaero-crystals. 



Aldrich [1901] proceeded like Takamine, but before precipitating the concentrated 

 solution with alcohol he added neutral lead acetate, centrifuged and removed the excess of 

 lead from the solution by means of hydrogen sulphide. Then, after concentration, he 

 added four to five volumes of 94 per cent, alcohol, evaporated the alcoholic filtrate to a very 

 small bulk and added ammonia ; after filtration the crude adrenaline is washed with 

 very dilute ammonia. 



Abel [1903, i] recommends a process illustrated as follows : 11*13 kilos, of minced glands 

 were divided over a number of flasks and to each portion an equal quantity of a solution of 

 175 grm. trichloracetic acid in 5 litres of absolute alcohol was added, in small quantities at 

 a time, with vigorous shaking. Next day 5-6 litres of filtrate were collected at the pump 

 and evaporated to 380 c.c. After filtering off a flocculent precipitate, ammonia (d = 0-94) 

 was gradually added to the clear filtrate with stirring until the smell of ammonia was per- 

 manent. The adrenaline, which separated at once, was filtered off and washed with water, 

 alcohol and ether ; yield 23-79 grm. = 0-2 per cent. The product, although nearly white, 



1 Those interested in this question of nomenclature may refer to a letter by T. Maben 

 in the Pharmaceutical Journal (1907, 78, 388-90 ; "Adrenalin : the Active Principle of the 

 Suprarenal Gland ") and to a reply by W. Martin in the same journal (1907, 78, 447 and 

 514 ; " Epinephrin or Adrenalin ? "), and particularly to a correspondence entitled " Pro- 

 prietary versus Unprotected Names " between the Council on Pharmacy and Chemistry of 

 the American Medical Association and Messrs. Parke, Davis & Co. (Journ. Amer. Med. Assoc., 

 1911, 56, 910-5). It is said that 30-40 different trade names for the active principle of 

 the supra-renal gland have been in use. Of these adnephrin, adrenalin, adrin, caprenalin, 

 supra-capsulin and supra-renalin are of American origin ; the following are European : atra- 

 bilin, chelafrinum, epirenan, haemostasin, hemisine, ischemin, paraganglin, paranephrin, 

 renoform, supra-nephran, supra-renaden, tonogen, and vaso-constrictin. Suprarenin is used 

 by the Ho'chst works for their synthetic product. 



