Patent GB-463698-A (GB)
Title: Process for the manufacture of a vitamin preparation
IPC: A61K31/44
Filed: 1935-10-04
Abstract: Vitamin H is extracted in a water soluble form from raw materials by a hydrolysis at temperatures above 100 DEG  C. and under pressure, preferably at a temperature between 120 and 300 DEG  C.  Raw materials mentioned as particularly rich in vitamin H are the liver and kidneys, although various other animal organs also contain the vitamin in lesser amounts.  The hydrolysis is always conducted in aqueous medium, and advantageously in the presence of water soluble organic diluents such as acetone and methyl and ethyl alcohol.  In addition to the organic diluents it is also preferred to conduct the hydrolysis in the presence of electrolytes.  These may be neutral such as sodium chloride or sulphate, ammonium chloride or sulphate, or potassium chloride, or acid such as dilute hydrochloric, sulphuric, phosphoric or acetic acid, or acid reacting salts such as sodium or potassium bisulphate, zinc chloride or iron sulphate, or alkaline such as sodium, potassium or magnesium hydroxide, baryta, milk of lime, sodium or potassium carbonate or acetate, or secondary or tertiary alkali metal phosphates.  The electrolytes particularly the alkali metal phosphates may also act as buffer substances. Instead of the crude raw materials there may be used preparations in which the vitamin H has been partially set free, but to an insufficient extent for practical purposes.  Such preparations may be obtained by subjecting raw materials containing the vitamin to a papaene digestion, or to a hydrolysis in a neutral medium at an elevated temperature under pressure.  After hydrolysis the product may be further purified by, for example, the removal of insoluble substances, or by absorption on an absorbent such as charcoal followed by elutriation with either acetone, aqueous pyridine, or mixtures containing pyridine, acetone, and methyl, ethyl, or isopropyl alcohol.  Other purification methods include a precipitation of ineffective accompanying substances by means of heavy metal salts such as mercury chloride or sulphate, uranyl acetate, or lead-acetate, or alternatively the vitamin component may be precipitated by means of phosphotungstic acid and the precipitate decomposed by baryta or milk of lime.  Acid or alkaline hydrolysis is preferred to neutral hydrolysis since the vitamin becomes thereby soluble not only in water, but also in organic solvents.  After either an acid or an alkaline hydrolysis neutralization is necessary before separation of the vitamin with organic solvents.  This separation may be carried out either by disintegration with water soluble organic solvents or by extraction with water insoluble solvents.  In the former case the active principle is dissolved, and the inactive components separate, usually in the form of an oil. Examples of water soluble solvents are ketones such as acetone, methyl-ethyl, and di-ethyl ketone, and alcohols such as methanol, ethanol, or isopropanol.  Examples of water insoluble solvents are pentanol, isopentanol, the butanols, and carboxylic esters such as ethyl and methyl acetates.  The solutions of the vitamin in organic solvents may, if desired, be again subjected to the purification processes described above.  A dry vitamin H preparation may be obtained by the evaporation of any of the solutions prepared as described above.  In examples: (1) Finely minced kidneys are heated with dilute hydrochloric acid at 140 DEG  C. under 3,5 atmospheres for 3 hours.  The liquor is drained and the treatment repeated.  The combined extracts are concentrated and filtered.  (2) Liver is exhaustively extracted with 40 per cent alcohol, dried, and heated at 160 DEG  C. under 6 atmospheres with water.  The residue is filtered and the extract concentrated.  (3) Liver powder is heated for 6 hours with water at 180 DEG  C. under pressure, filtered, concentrated, and then boiled with dilute sulphuric acid for 6 hours.  The product is neutralized and acetone added.  The acetone solution is separated from the dark oil, and concentrated.  A mixture of acetone and propanol may be used instead of acetone. If desired a precipitation with phosphotungstic acid followed by decomposition with baryta may be interposed between the acid hydrolysis and the acetone treatment. (4) Liver powder is heated with dilute sulphuric acid at 160 DEG  C. under pressure for 4 hours, neutralized without filtering with caustic soda, and after concentration, treated with ethyl acetate. The ester solution is separated from the dark sediment and concentrated.  (5) Liver powder is heated at 150 DEG  C. under pressure for 4 hours with dilute caustic soda.  The gelatinous mass is washed with water, neutralized, concentrated, and then acetone is added.  The oily sediment is separated and the clear layer evaporated to dryness, dissolved in water and filtered from sediment.