Patent GB-808272-A (GB)
Title: Preparation of aqueous solutions of normally water-insoluble organic substances
IPC: A61K47/14
Filed: 1955-01-17
Abstract: An aqueous solution of a normally water-insoluble unsaturated fatty acid or fatty acid ester having at least one olefinic double bond, especially one containing conjugated double bonds, is obtained by bringing the unsaturated substance into close interaction by mechanical means with a multiple excess of water, under non-oxidizing conditions, continuing such interaction until some of the unsaturated substance is converted into a water-soluble form and is dissolved in the aqueous phase, and separating the aqueous phase containing said water-soluble form from the insoluble residue.  A high rate of stirring is generally required but the formation of bubbles and foam should be avoided. Stirring for 30 to 150 minutes at several hundred revolutions per minute will generally suffice.  In order to avoid oxidation during the process the water used should preferably be free of air, and all catalysts which encourage oxidation, e.g. heavy metal ions, should be excluded.  The process can also be carried out in an atmosphere of protective gas, e.g. nitrogen, and in this case the close interaction may be effected by mechanical shaking.  If the unsaturated substance is solid or viscous at room temperature it is desirable to carry out the process at a raised temperature at which the starting material is liquid.  In an example a mixture comprising linoleic, linolenic and oleic acids and a small amount of saturated fatty acids, obtained from pure linseed oil, is mechanically stirred with a hundredfold quantity by weight of air-free water for 1 hour at 60-70 DEG  C.  The separated aqueous phase is a solution containing unsaturated fatty acid and after evaporation of the water a clear yellow amorphous mass is obtained which is soluble in water although with difficulty.  The ultraviolet spectrogram of the separated aqueous phase suggests the presence of conjugated fatty acids.ALSO:An aqueous solution of a normally waterinsoluble unsaturated fatty acid, fatty acid ester, ketone or aldehyde having at least one olefinic double bond, especially one containing conjugated double bonds, is obtained by bringing the unsaturated substance into close interaction by mechanical means with a multiple excess by weight of water, under non-oxidizing conditions, continuing such interaction until some of the unsaturated substance is converted into a water-soluble form and is dissolved in the aqueous phase, and separating the aqueous phase containing said water-soluble form of the unsaturated substance from the insoluble residue.  A high rate of stirring is generally required and in general stirring for 30 to 150 minutes at several hundred revolutions per minute will suffice.  In order to avoid oxidation during the process the formation of bubbles and foam should be avoided and the water used should preferably be free of air.  The process can also be carried out in an atmosphere of protective gas, e.g. nitrogen, and in this case the close interaction may be effected by mechanical shaking.  All catalysts which encourage oxidation, e.g. heavy metal ions, should be excluded.  If the unsaturated substance is solid or viscous at room temperature it is desirable to carry out the process at a raised temperature at which the starting material is liquid.  In one example citrus oil from lemon peel is mechanically stirred at about 1400 r.p.m. with a hundredfold excess by weight of air-free water at room temperature for 30 to 60 minutes in a container with a ground glass stopper through which the stirring shaft is led.  The resulting emulsion is allowed to stand in a separating funnel for 24 hours and the aqueous phase is then separated and filtered through very close textured filter paper to give a clear, colourless, solution having an intensive odour of citral.  An ultra-violet spectrogram of this solution indicates the presence of a substance containing the conjugated system -C=C-C= O and it is stated that the water-soluble portion contains predominantly citral in water-soluble form as well as higher fatty acids.  On evaporating the water citral evaporates with the water vapour leaving a glossy-amorphous residue comprising the higher fatty acids which can easily be dissolved in water.  If, however, the aqueous solution is extracted with a fat solvent such as ether or cyclohexane the non-aqueous substances are taken up by the solvent and on evaporation of the solvent a mixture of citral and the fatty acids is obtained which is not water-soluble.  It is stated that similar results are obtained with orange-peel oil, grape-fruitpeel oil and sandalwood oil.  In another example a mixture comprising linoleic, linolenic and oleic acids and a small amount of saturated fatty acids, obtained from pure linseed oil, is mechanically stirred as in the above example with a hundredfold quantity by weight of airfree water for 1 hour at 60-70 DEG  C.  The separated aqueous phase is a solution containing unsaturated fatty acids and after evaporation of the water a clear yellow amorphous mass is obtained which is soluble in water although with difficulty.  The ultra-violet spectrogram of the separated aqueous phase suggests the presence of conjugated fatty acids.  The aqueous solutions may be used for medicinal application (see Group VI).ALSO:An aqueous solution of a normally water-insoluble unsaturated fatty acid, fatty acid ester, ketone or aldehyde, having at least one olefinic double bond, especially one containing conjugated double bonds, may be used for medicinal application, e.g. for intravenous injection.  The aqueous solution is obtained (see Group IV (b) by bringing the unsaturated substance into close interaction by mechanical means with a multiple excess by weight of water under non-oxidizing conditions, continuing such interaction until some of the unsaturated substance is converted into a water-soluble form and is dissolved in the aqueous phase and separating the aqueous phase containing said water-soluble form from the insoluble residue.  Examples are given for the processing of citrus oil (from lemon peel) to form an aqueous solution containing citral and for the treatment of a mixture obtained from pure linseed oil and comprising linoleic acid, linolenic acid, oleic acid and a small amount of saturated fatty acids to form an aqueous solution containing unsaturated fatty acids.  Other specified substances which may be used to form the aqueous solutions are orange-peel oil, grapefruit-peel oil and sandalwood oil.