Patent GB-585573-A (GB)
Title: Improvements in or relating to the production of fat-soluble vitamin concentrates
IPC: A61K31/59
Filed: 1943-07-09
Abstract: Vitamin concentrates, essentially vitamins A and D, stated to be of improved potency and taste and odour, one rich in vitamin alcohols and one rich in vitamin esters, are obtained by partially and selectively saponifying a vitamin containing marine oil (or a solvent extract thereof, e.g. in isopropanol) with an amount of alkali insufficient to saponify more than 95 per cent, but sufficient to saponify at least 60 per cent of the saponifiable matter, treating the partially saponified mass with a non-polar solvent in the presence of sufficient water to form a separate aqueous soap phase, separating the latter from the solvent extract containing the vitamins, removing the solvent as by evaporation to leave a semi-concentrate; and separating the semi-concentrate into a concentrate on fraction in which the vitamin matter is present mainly as vitamin esters and a fraction in which it is present mainly as vitamin alcohols by extraction with a solvent miscible with vitamin alcohols and immiscible with vitamin esters. Specified fish liver oils are: cod, ling cod, pollack, tuna, shark, dogfish, mackerel, sword-fish, spear-fish, grey fish, sole and halibut.  Other specified marine oils are: sardine, pilchard, herring, seal and whale. Specified alkalies are: sodium and potassium hydroxide, sodium and potassium carbonate. Advantageously, the rate of saponification is retarded to enhance the selective saponification of the non-vitamin esters in preference to the vitamin esters, e.g. by adjusting the concentrations of the solvent, catalyst and caustic alkali. Specified solvents are: ethylene dichloride, heptane, trichlorethylene, hexane, cyclohexane, methyl cyclohexane or mixtures thereof.  Specified catalysts are: isopropanol or other polar catalyst.  The saponification may, however, take place without catalyst or solvent, but when a solvent is used it is preferable to use the same solvent in treating the partially saponified mass.  The fractionation of the semi-concentrate may be effected alternatively as follows: (1) it is treated with a highly polar solvent like methanol to extract mainly the vitamin alcohols and to leave vitamin esters in the semi-concentrate; (2) as in (1), but the residual semi-concentrate is treated with a moderately polar solvent like isopropanol advantageously by cooling sufficiently to separate solid matter and removing the solvent from the liquid portion as by evaporation; (3) it is treated with a moderately polar solvent such as isopropanol and the resulting extract resolved into ester and alcohol concentrates by fractionation with a highly polar solvent such as methanol.  In place of or in combination with methanol (or ethanol) there may be used: isopropanol, isobutanol, n-butanol, acetone and diacetone alcohol, each of which has been modified by the addition of at least 9 per cent water, methanol and/or ethanol; or, in general, any other solvent which is characterised by being miscible with vitamin alcohols, but immiscible with vitamin esters advantageously on cooling.  In place of the moderately polar solvent, there may be used any aliphatic polar solvent characterised by being miscible with the semi-concentrate, or the residual fraction thereof as in (2) above, at temperatures above room temperature and at least partially immiscible therewith at temperatures below room temperature, e.g. acetone, diacetone alcohol and n-butanol.  In examples: (1) shark liver oil is saponified by heating with sufficient aqueous potash to bring about 85 per cent saponification in the presence of ethylidene dichloride and isopropanol.  The partially saponified mass is treated with ethylidene dichloride and a little water and cooled to separate the solvent layer which is supplemented by further solvent extractions of the soap layer.  The solvent is evaporated under reduced pressure to obtain the semi-concentrate which is treated with methanol at 50 DEG  C.  On cooling the mixture to -18 DEG  C., a methanol layer containing vitamin alcohol separates from the vitamin ester layer and is supplemented by further methanol extractions from the ester layer before the methanol is removed by fractional distillation to obtain the vitamin A alcohol concentrate.  The vitamin ester fraction is purified by dissolving it in isopropanol at 41 DEG  C., cooling the mixture to -18 DEG  C., filtering, thereby leaving a residue which is further extracted with isopropanol, and the filtrates are combined.  Vitamin A ester concentrate is obtained from the filtrates by distilling off the solvent under reduced pressure in an atmosphere of nitrogen and is also found in the residues left on the filter.  (2) Vitamin semi-concentrate prepared as in (1) is subjected to an isopropanol extraction under similar conditions to those used in example (1). (3) Vitamin semi-concentrate prepared as in (1) is treated with methanol at room temperature to extract the vitamin A alcohol leaving a vitamin A ester residue, the extraction being repeated and the extracts combined as in (1) and (2).  (4) to (7) Vitamin semi-concentrates and vitamin A concentrates are prepared as in (1), (the oil being treated with varying amounts of potash, thereby effecting saponification to different degrees producing concentrates having correspondingly varying vitamin strengths and yields of vitamin ester) except in that: the isopropanol extraction and succeeding steps are omitted; and, in (7), saponification is effected without a solvent and the semi-concentrate is extracted with methanol at -18 DEG  C.  (8) Vitamin semi-concentrate is prepared as in (7), the isopropanol being diluted with 1 per cent water.  The semi-concentrate is fractionated as in (1) to (6), the ethanol containing 5 per cent of water being used instead of methanol.  (9) Greyfish liver oil is treated with sufficient 45 per cent aqueous potash to saponify about 95 per cent of the oil, in the absence of solvent and catalyst and in a nitrogen atmosphere.  The resulting soap mass is treated as in (7) to obtain a semi-concentrate which is fractionated into vitamin A alcohol and ester concentrates by extraction with methanol.  Specifications 528,994 and 558,820 are referred to.  The Specification as open to inspection under Sect. 91 includes also unrestricted partial saponification of the marine oil and by the use of saponifying agents other than alkalies, e.g. enzymes. It also includes the separation of the unsaponified fraction from the saponified matter and the separation of the vitamin alcohols from the vitamin esters without restriction of the method of separation.  It is disclosed in particular that the semi-concentrate may be fractionated by high vacuum distillation or by adsorption.  This subject-matter does not appear in the Specification as accepted.