Patent GB-693162-A (GB)
Title: Amino acid solutions and process of preparing the same
IPC: A61K31/195
Filed: 1949-05-25
Abstract: Amino acid solutions for parental injection are prepared by neutralizing an aqueous solution of the basic amino acids arginine, histidine and lysine to a pH within the range 4.5 to 8 by the addition of an innocuous physiological organic acid viz. any of the group of organic acids which are assimilated and utilized by the body or organic acids which are found in the metabolism of food stuffs and thus occur normally in the body, which when introduced into the blood stream in high concentration produces no untoward side reactions such as nausea, vomiting or loss of calcium.  Specified organic acids are acetic, lactic, pyruvic and 1-pyrrolidone carboxylic acids.  In examples, casein is subjected to acid hydrolysis, the hydrolysate treated with an anion exchanger to remove the acid catalyst, extracted with butanol to remove the mono-amino monocarboxylic acid fraction, cooled to precipitate tyrosine and treated with a cation-exchanger to recover the basic amino acid mixture of lysine, arginine and histidine all in accord with the process of Specification 692,922, whereupon (2) portions of the mono-amino and basic amino acids are dissolved in a quantity of distilled water, the pH adjusted to 7 by means of lactic acid, then glycine added and the pH readjusted to 7.4 by addition of lactic acid followed by various additions to form the solution to be injected (see Group VI); (3)-(5) the lactic acid is replaced by glacial acetic, 1-pyrrolidone carboxylic and pyruvic acids respectively.  Specification 652,237 is also referred to.  The Specification as open to inspection under Sect. 91, is not restricted to neutralization to the above-mentioned pH.  This subject-matter does not appear in the Specification as accepted.ALSO:Amino acid solutions for parenteral injection are prepared by a process comprising neutralizing an aqueous solution of the basic amino acids arginine, lysine and histidine to a pH within the range 4.5 to 8 by the addition of an innocuous physiological organic acid viz., any of the group of organic acids which are assimilated and utilized by the body or are formed in the metabolism of foodstuffs and thus occur normally in the body, which when introduced into the blood stream in high concentration produces no untoward side-reactions such as nausea, vomiting or loss of calcium. Specified organic acids are acetic, lactic, pyruvic and 1-pyrrolidone carboxylic acids.  The solutions are better tolerated than those where hydrochloric acid is the neutralising agent.  In examples, casein is subjected to acid hydrolysis, the hydrolysate treated with an anion exchange resin to remove the acid catalyst, cooled to precipitate tyrosine, extracted with butanol to remove the mono-amino mono carboxylic acid fraction and then treated with a cation-exchange resin to recover the basic amino acids lysine, histidine and arginine, all in accordance with the process of Specification 692,922; whereupon: (2) portions of the mono-amino mono-carboxylic acid fraction and basic amino acid mixture are dissolved in a quantity of distilled water, lactic acid added to pH 7, then glycine is added and the pH adjusted to 7.4 by means of lactic acid whereafter the solution is freed of oxygen, d l-tryptophane and sodium bisulphate added and the solution is finally sterilised; (3)-(5), the lactic acid is replaced by glacial acetic acid, 1-pyrrolidone carboxylic acid and pyruvic acid respectively. Specification 652,237 also is referred to.  The Specification as open to inspection under Sect. 91 is not restricted to neutralization to the above-specified pH.  This subject-matter does not appear in the Specification as accepted.