Patent GB-618406-A (GB)
Title: Improvements in or relating to processes of producing plant extracts and the products resulting therefrom
IPC: A61K36/185
Filed: 1944-05-03
Abstract: A crystalline compound comprising 85-90 per cent pure nordihydroguaiaretic acid obtained by extraction of plants of the species Larrea divaricata (creosote bush) is added to lard as an antioxidant and preservative in concentrations of about 0.01 per cent.ALSO:Extracts containing substantial proportions of nordihydroguaianetic acid <FORM:0618406/IV(b)/1> from plants of the species Larrea divaricata are prepared by treating the plant material with an organic solvent to form a primary or crude extract which may be purified by treating with an aqueous solution of an inorganic alkali; or by extracting the plant material with an aqueous solution of an alkali metal hydroxide, e.g. sodium hydroxide or potassium hydroxide, acidulating the resultant solution and separating the nordihydroguaianetic acid-containing precipitate.  In the solvent extraction method powdered plant material is treated with a solvent capable of giving extracts showing a positive reaction for catechol when tested with ferric chloride, e.g. organic halogen, nitrogen or oxygen compounds.  Diethyl ether is preferred.  The solvent is removed by evaporation and the extract is redissolved in a water immiscible solvent such as ether.  The extract may be further purified by washing with alkaline bicarbonates or carbonates in the presence of a reducing agent, preferably sodium hydrosulphite, when the stronger alkali is used.  In the extraction with aqueous alkali metal hydroxide the whole plant is leached with a 2-10 per cent solution of the alkali containing a reducing agent to prevent oxidation and the extract is neutralised with acid; a flocculent precipitate forms which is dissolved directly in an ether such as diethyl or isopropyl ether or is dissolved in an alcohol having not more than 3 carbon atoms, is washed with water to remove the alcohol and is then transferred to an ether solution.  The extracts prepared by either of the above methods are finally purified by treating with aqueous alkali metal hydroxide either in one step or preferably in successive small portions and in the presence of a strong reducing agent, e.g. sodium hydrosulphite, to prevent oxidation of the phenolic compounds.  Each extract fraction is acidified and where ether is used as a solvent, may be heated on a water bath to remove ether. On standing a solid residue separates out.  The nordihydroguaianetic acid, as shown by testing with ferric chloride, is concentrated in the last fractions, from which it is ultimately obtained as a distinctly crystalline substance of 85-95 per cent purity.  It is used as a germicide and anti-oxidant.  In examples: (1) dried, powdered Larrea divaricata is extracted with ether and separated by successive treatment with aqueous solutions of sodium bicarbonate, sodium carbonate and sodium hydroxide, the latter two compounds being used in the presence of sodium hydrosulphite, giving on acidification of the later sodium hydroxide extracts, nordihydroguaianetic acid of 88 DEG  C. purity; (2) and (3) the plant material is extracted with ethylene dichloride, sodium bicarbonate solution containing sodium hydrosulphite is added, the mixture is evaporated to near dryness, redissolved in ether and separated as in (1); (4) dried plant material is extracted with sodium hydroxide-sodium hydrosulphite and neutralised giving a flucculent precipitate which is separated, dissolved in methyl alcohol, acidified with hydrochloric acid, diluted with ether, washed with water and separated by successive treatments with aqueous potassium hydroxide; and (5) green plant material is subjected to the extraction process of (4).ALSO:Extracts of plants of the species Larrea divaricata containing substantial portions of nordihydroguaiaretic acid are prepared by treating the plant material with an organic solvent to form a primary extract which is purified by washing, with an aqueous solution of inorganic alkali; or by reacting the plant material with an aqueous solution of an alkali metal hydroxide, e.g. sodium or potassium hydroxide, acidulating and separating the nordihydroguaiaretic acid-containing precipitate.  In the solvent extraction method powdered plant material is treated with a solvent for the nordihydroguaiaretic acid fractions, suitably an organic nitrogen, oxygen or halogen compound, such as diethyl ether, the solvent is removed by evaporation the extract is redissolved in a water immiscible solvent such as ether and, if desired, the solution is purified by washing with mild aqueous alkali.  In the extraction with aqueous alkali metal hydroxide the plant is leached with a 2 - 10 per cent solution of the alkali containing a reducing agent such as sodium hydrosulphite to prevent oxidation, the extract is acidified to give a flocculent precipitate which is separated and dissolved in a water immiscible solvent such as ether.  The extracts prepared by either of the above methods are purified by treating with aqueous alkali metal hydroxide in the presence of a reducing agent, either in one step, or preferably in successive small portions and the extract fractions are acidified to give a nordihydroguaiaretic acid containing precipitate.  Where the final alkali treatment is carried out in successive small fractions the nordihydroguaiaretic acid is concentrated in the last fractions from which it may be obtained as a crystalline substance of 85 - 90 per cent purity.  The crystalline material is a germicide. In examples (1) dried powdered Larrea divaricata is extracted with ether, washed with sodium bicarbonate and sodium carbonate and treated with successive portions of aqueous sodium hydroxide to give extracts which on acidifying yield nordihydroguaiaretic acid of 88 per cent purity; (2) and (3) the plant material is extracted with ethylene dichloride, evaporated to near dryness, redissolved in ether and treated as in (1); (4) the dried plant material is extracted with sodium hydroxide in the presence of sodium hydrosulphite, acidified to give a precipitate which is dissolved in methyl alcohol transferred to ether solution and separated by successive treatments with potassium hydroxide; and (5) green plant material is extracted as in (4).