AQUEOUS SOLUTION OF FAT-SOLUBLE SUBSTANCE

Abstract: An aqueous solution comprises a fat-soluble substance, a phosphatide, a polyhydric alcohol and a basic amino acid, a salt thereof or Meglumin. It is uniformly emlulsified and solubilized for the pharmaceutical use.

Description: The invention relates to an aqueous solution of a fat-soluble substance, for example, a fat-soluble vitamin, and provides a solution, uniformly emulsified or solubilized, which is obtained even with mild stirring. In the state of the art, an aqueous solution of a fat-soluble substance, a phosphatide and a polyhydric alcohol is obtained with the use of a high pressure homogenizer, a ultrasonic emulsifying machine for a long time such as 60 minutes. This strong dispersing power is indeed necessary which is why mass-production cannot be conducted. In the invention, instead of such a machine, a device effecting mild stirring, for example Polytron® and a homomixer, is available to offer a mild share stress. Alternatively an ultra-sonic emulsifying machine can be used for a short time. This can be advantageously attained with incorporation of a basic amino acid, a salt thereof or Meglumin into the solution. The invention provides an aqueous solution which comprises a fat-soluble substance, a phosphatide, a polyhydric alcohol and a basic amino acid, a salt thereof or Meglumine. Thus, the invention provides an aqueous solution comprising: (a) a fat-soluble substance selected from vitamin E acetate, coenzyme Q10, vitamin A, an aliphatic ester of vitamin C, emulsified or solubilized in the aqueous phase; (b) a phosphatide selected from soy bean lecithin and egg yolk lecithin; (c) a polyhydric alcohol selected from glycerin and D-sorbitol; d) 0.1 to 0.5 parts by weight, per 1 part of (b) of a basic amino acid selected from L-arginine, L-lysine or a salt thereof or Meglumine (N-methylglucamine); and (e) water. Fig. 1 shows results of Test III. Example 1 An aqueous solution was prepared in the following way. Solution A comprising 100 mg of vitamin E acetate, 30 mg of L-arginine, 100 mg of purified soy bean lecithin and 770 mg of glycerine was prepared with a Polytron®. 19 of Solution A was mixed with 12 ml of purified water, while stirred. Mixture B comprising 0.5 ml of ginseng extract liquid, 25 mg of nicotinamide, 10 mg of FMN(VB2), 50 mg of caffein, 3000 mg of D-sorbitol, 5000 mg of purified white sugar, 18 mg of benzoic acid, 20 mg of dl-malic acid and a suitable amount of sodium citrate was dissolved in 12 ml of purified water. Mixture D comprising 3 mg of ethyl paraben, 1 ml of ethanol and a trace of a perfume was added to and mixed with the Solution B. Solutions A and B were mixed together and the mixture was adjusted with sodium citrate to a pH of 5.5. More purified water was added to a total volume of 30 ml. The final liquid was found to be transparent and clear. Example 2 Mixture B comprising 0.3 g of Meglumin, 6.9 g of glycerine and 0.8 ml of ethanol was heated to obtain a solution. Mixture A comprising 1.0 g of soy bean oil and 1.0 g of soy bean phosphatide was added to Solution B. A clear solution was obtained with the use of a Polytron®. Example 3 3 mg of Meglumin was dissolved in a mixture of 27 mg of glycerine and 50 mg of a 70% solution of D-sorbitol. 10 mg of coenzyme Q and 10 mg of purified egg yolk lecithine were added to the solution. The mixture was treated with a Polytron® to an aqueous solution. The solution was further diluted with water and adusted with a suitable amount of citric acid solution in purified water for injection to a pH of about 7 and obtain 1 ml of a clear injectable liquid. Test I The aqueous solutions listed in Table 1 were prepared and examined for water dispersibility. The components 1 and 4 were dissolved in water, while heated. Then components 2 and 3 were added to the solution. The mixture was treated with a Polytron® at 7000 RPM for 30 minutes. The obtained solutions were observed in respect to their appearance. A 3 % dispersion of each solution in water was obtained and it was observed. Moreover it was determined in view of transmittance of light at O.D. 640 nm. The composition 1 is control and the compositions 2 and 3 fall within the invention. The composition 1 was found to have oil and lecithin drops floating on the surface. Test II Aqueous solutions were prepared, as listed in Table 2, with different of amounts of L-arginine. They were tested for water dispersibility. The results are shown in Table 2. L-arginine was dissolved in glycerine with heating. Then, soy bean lecithin and vitamin E acetate were added to the solution and the mixture was treated with a Polytron® at 7000 RPM for 30 minutes. They were observed in appearance. A 3% aqueous solution of each resultant was determined in view of transmittance of light at O.D. 640 nm. Ratios in the uppermost column show those of L-arginine to lecithine. In the test on 0/10 in transmittace, some oil was found to separate out. Test III Aqueous solutions were prepared containing different ratios of L-arginine to soy bean lecithin. The L-arginine was dissolved, while heated, in glycerin. Soy bean lecithin and vitamin E acetate were then added to the solution and the mixture was stirred with an ultra-sonic emulsifying machine for 90 seconds. The thus obtained aqueous liquids were adjusted to have a concentration of 3 % by weight. They were tested in view of light transparency at O.D. 640 nm. The results given in Fig. 1 show that addition of L-arginine was found to be advantageous in comparison with no addition.

Claims: Claims for the following Contractings States : AT, BE, CH, DE, FR, GB, IT, NL, SE 1. An aqueous solution comprising: (a) a fat-soluble substance selected from vitamin E acetate, coenzyme Q10, vitamin A, an aliphatic ester of vitamin C, emulsified or solubilized in the aqueous phase; (b) a phosphatide selected from soy bean lecithin and egg yolk lecithin; (c) a polyhydric alcohol selected from glycerin and D-sorbitol; (d) 0.1 to 0.5 parts by weight, per 1 part of (b) of a basic amino acid selected from L-arginine, L-lysine or a salt thereof or Meglumine (N-methylglucamine); and (e) water. 2. The use of an aqueous solution according to Claim 1 for preparing an injection liquid, an emulsion or an oral preparation. Claim for the following Contracting State : ES 1. A method for preparing an injection liquid, an emulsion or an oral preparation, characterized in that an aqueous solution is used comprising (a) a fat-soluble substance selected from vitamin E acetate, coenzyme Q10, vitamin A, an aliphatic ester of vitamin C, emulsified or solubilized in the aqueous phase; (b) a phosphatide selected from soy bean lecithin and egg yolk lecithin; (c) a polyhydric alcohol selected from glycerin and D-sorbitol; (d) 0.1 to 0.5 parts by weight, per 1 part of (b) of a basic amino acid selected from L-arginine, L-lysine or a salt thereof or Meglumine (N-methylglucamine); and (e) water.

Inventors: OHSAWA, SHIGEMITSU, SHIBUSAWA, KOICHI
Applicants: EISAI CO., LTD.
Application year: 1989
Main classification: A61K47
IPC codes: A61K47, A61K9, A61K31