JPS62419A - Water-soluble agent containing fat-soluble vitamin - Google Patents

Abstract

PURPOSE:To obtain the titled water-soluble agent having extremely high stability and excellent safety and takable without feeling the taste and odor, by compounding a fat-soluble vitamin, a water-soluble polyhydric alcohol, a polyglycerol fatty acid ester, ethanol and water. CONSTITUTION:The objective water-soluble agent can be produced by compounding (A) preferably 0.5-30(wt)% fat-soluble vitamin (e.g. vitamin A, D, E, F, K, U, etc.), (B) preferably 2-95% water-soluble polyhydric alcohol having >=2 OH groups in the molecule (e.g. ethylene glycol), (C) preferably 0.2-5pts. (based on 1pt. of the component A) of a polyglycerol fatty acid eater (preferably having a glycerol polymerization degree of 6-15), (D) preferably 0.5-20% ethanol and (E) preferably 0.1-5pts. (based on 1pt. of the component B) of water.

Description

[Detailed Description of the Invention] [Industrial Application Field] The present invention provides a method for producing a polyhydric alcohol, which is produced using a water-soluble polyhydric alcohol, a polyglycerol fatty acid ester, ethanol, and water.
The present invention relates to a stable water-soluble agent containing fat-soluble vitamins.

[Conventional technology]

Fat-soluble vitamins are widely used in the pharmaceutical, cosmetic, and food fields, but since these vitamins hardly dissolve in water, they must be mixed with fats and oils using a nonionic surfactant to make them water-soluble. Operations such as emulsification or solubilization in an aqueous alcohol solution are required. Therefore, the present inventors attempted to create a water-soluble agent for fat-soluble vitamins using polyglycerin fatty acid ester, which is a nonionic surfactant that is permitted in the food field as well as in pharmaceuticals and cosmetics. An example of a formulation made from a combination of fat-soluble vitamins and polyglycerin fatty acid esters is disclosed in JP-A-58
-13508 publication is known.

[Problem that the invention seeks to solve]

Conventional water-soluble formulations of fat-soluble vitamins have problems with stability when incorporated into aqueous solutions such as injections, eye drops, lotions, and drinks. This is a phenomenon that occurs in emulsified systems, where fat-soluble components float out over time, a so-called creaming phenomenon, and in solubilized systems, the system breaks down and fat-soluble vitamins precipitate. In view of these circumstances, the present inventors developed a microemulsion of fat-soluble vitamin emulsion particles with a size of 0.5μ or less, thereby making it possible to stably incorporate fat-soluble vitamins into an aqueous solution system in any proportion. It has been discovered that it is possible to create a water-soluble agent containing This is based on the Stokes sedimentation velocity equation, which corresponds to the fact that the smaller the particle size, the lower the sedimentation speed of the particles.As the particle size becomes smaller, the emulsion becomes translucent to transparent in appearance. Even when diluted, cloudiness does not occur, which is preferable in terms of product design.

Based on this knowledge, the present inventors conducted extensive research and found that fat-soluble vitamins, one or more water-soluble polyhydric alcohols having two or more hydroxyl groups in the molecule, and polyglycerin fatty acid esters, Combine ethanol and water,
It was discovered that a water-soluble agent containing fat-soluble vitamins in which fat-soluble vitamins are microemulsified can be obtained by treatment with a pressure homogenizer, and the present invention was completed.

The emulsion thus produced is very stable and has excellent safety, and there is no problem with taste or odor when it is eaten or eaten.

Means for Solving Problem C] That is, the present invention comprises one or more fat-soluble vitamins, one or more water-soluble polyhydric alcohols having two or more hydroxyl groups in the molecule, This is a water-soluble agent containing fat-soluble vitamins that contains polyglycerol fatty acid ester, ethanol, and water.

Hereinafter, the configuration of the present invention will be explained in detail.

The fat-soluble vitamins in the present invention include vitamin A,
There are D, E, F, K and U, and the blending amount is 0.1 to 50% by weight, preferably 0.5 to 30% by weight.

In addition, the water-soluble polyhydric alcohols having two or more hydroxyl groups in the molecule used in the present invention include ethylene glycol, propylene glycol, 1,3-butylene glycol, 1,4-butylene glycol, dipropylene glycol, glycerin and Diglycerin, triglycerin, tetraglycerin, glucose, maltose, maltitol, M sugar, fructose, xylitol, sorbitol, maltotriose, threitol, Eris IJ
), starch decomposition sugar, starch decomposition sugar reducing alcohol, etc., and the blending amount of these is preferably 2 to 95% by weight.

Polyglycerin fatty acid ester has HLB depending on the degree of polymerization of glycerin, the type of fatty acid, and the degree of esterification.
Although it can be made from high to low glycerin, it is preferable to use glycerin with a polymerization degree of 6 to 15. If the degree of polymerization is 5 or less, HLB will be too low and 16
If it is more than that, the viscosity becomes too high and it becomes difficult to handle. In addition, fatty acids can be selected from natural products to synthetic ones, such as stearic acid, myristic acid, oleic acid, lauric acid, valmitic acid, diisostearic acid, linoleic acid, and lylunic acid. , diesters are preferred.

The amount of polyglycerin fatty acid ester blended is preferably 115 to 5 times the amount of fat-soluble vitamins.

Further, the blending amount of ethanol is preferably 0.5 to 20% by weight, and if it is less than 0.5% by weight, the effect of blending is not so great, and if it is 20jlfffi% or more, the stability of the emulsion is impaired, so it is not so preferable. Next, water is added to this and subjected to pressure homogenization to obtain a microemulsion of fat-soluble vitamins. If necessary, a portion of the water is added to the aqueous phase component and the remaining water is extracted after pressure homogenization. You can also add water while stirring.

At this time, the initial amount of water used is preferably 1/10 to 5 times the amount of water-soluble polyhydric alcohol. In the present invention, in addition to the above-mentioned essential components, natural products such as lecithin, saponin, casein, and gelatin can also be added to the system.

The present invention can be widely applied to medicines, cosmetics, and foods. For example, it can be used as is or in diluted form to produce cosmetics such as skin lotions, astringent lotions, softening lotions, hair tonics, milky lotions, creams, and foundations, pharmaceuticals such as injections, eye drops, and urea creams, juices, It can be added to foods such as drinks.

Emulsification in the present invention can be carried out using a normal stirring emulsifying machine, but preferably a Manton Galarin homogenizer (Manton Galarin Co., Ltd. Type 15M-8T, USA)
A microemulsion with finer particles can be obtained by emulsifying under high shear force using a pressure emulsifier such as A). In the production of the fat-soluble vitamin-containing water-soluble agent of the present invention, an isotonizing agent, a buffering agent,
A solubilizing agent, a flavoring agent, a preservative, a stabilizer, a specific gravity adjuster, etc. can be further added as appropriate. In addition, the water-soluble agent containing fat-soluble vitamins of the present invention usually has an average of 0.
．． It consists of fine emulsified particles with a diameter of 5μ or less, can withstand heat sterilization, and has excellent physical stability over time.

(Example) Next, an example will be shown to explain the present invention in more detail. Note that the present invention is not limited to this. The blending amount is 9% by weight.

Example 1 ■ Mabisoto 30■
Decaglycerin monooleate 10 ■ Natural vitamin E 10 ■
Ethyl alcohol 2■ Citric acid 0.1■ Purified soybean lecithin 2■ Sodium benzoate 0.2■ Ion exchange water
Part (10ii%) of ■, ■, ■, ■, ■, ■ are sequentially added to the remainder (lA method) to ■, mixed and dissolved at room temperature, and ■ is added thereto with stirring. , Manton Galarin Homogenizer-50
The treatment is carried out 8 times under a pressurizing condition of 0 kg/cJ. Furthermore,■
The remainder (36.7% by weight) was added with stirring to obtain a vitamin E-containing water-soluble agent.

(Stability evaluation) The fat-soluble vitamin-containing water-soluble agents of the present invention obtained in Examples 1 to 5 were mixed in ion-exchanged water at a ratio of 5%, and after being left at room temperature for one month, the stability was evaluated. Evaluation was made with the naked eye. The results are shown in Table 1, with 0 indicating no creaming or separation, and x indicating creaming or separation.

Comparative Example 1 was similarly evaluated and shown in Table 1.

Example 2 ■ Glycerin 40 ■ Hexaglyceride diisostearate 15 ■ Vitamin A5 ■ Ethyl alcohol 10 ■ E
D T A O, 0
5 ■ Citric acid 0.
10 Sodium benzoate 0.2
■ Ion-exchange water residue (manufacturing method) Add ■, ■, ■, ■, ■, ■ sequentially to ■, mix and dissolve at room temperature, add ■ to it while stirring, and add it using a Manton Galarin homogenizer The treatment was carried out 10 times under a pressure condition of -500 kg/d to obtain a vitamin A-containing water-soluble agent.

Example 3 ■ Sorbitol 35 ■ Pentadecaglycerin monostearate 10 ■ Vitamin D 12 ■
Ethyl alcohol 20 ■ Sodium hexametaphosphate 0.02 ■ Lecithin 5 ■ Citric acid
0.1■ Sodium benzoate
0.2 ■ Ion exchange water
Residue (manufacturing method) Add ■, ■, ■, ■1, ■, ■, ■ to the remaining ■ in order,
Mix and dissolve at room temperature, add ① to it while stirring, and use a Manton Galarin homogenizer 500 kg/a.
The treatment was carried out five times under a pressure condition of nt to obtain a vitamin D-containing water-soluble agent.

Example 4 ■ Mabitton 15 ■ Decaglycerin monooleate 7 ■ Natural vitamin E 80% 5 ■ Schroth acetate isobutyrate 3 ■ Ethyl alcohol 0.5 ■ Sodium benzoate 0.20 Citric acid
0.1 ■ Ion exchange water
Residue (manufacturing method) Part (20% by weight) of ■, ■, ■, ■, and ■ were sequentially added to the remaining ■, mixed and dissolved at room temperature, and the mixture of ■ and ■ was stirred. Add and process 6 times using a Manton Galarin homogenizer at 500 kg/crM. Further, the remaining part (49.8% by weight) of (1) was added with stirring to obtain a vitamin E-containing water-soluble agent.

Example 5 ■ Propylene glycol 25 ■ Decaglycerin monolaurate 5 ■ Vitamin E8 ■ Ethyl alcohol 5 ■ Citric acid 0.1 ■ Sodium benzoate 0.20 Ion exchange water Remainder (manufacturing method) ■, ■, ■ ,■,■-m (25ffiit%)
were added sequentially, mixed and melted at room temperature, and then added with stirring, using a Manton Galarin homogenizer 5.
00 kg/ctA, treated 4 times. Furthermore, add the remainder of (29% by weight) of ■ while stirring, and add vitamin E.
A containing water-soluble agent was obtained.

Comparative example 1 ■ Vitamin E 5.0 ■ Squalane 3.0 ■
Vaseline 2.0■ Sorbitan sesquioleate 1.6■ Polyoxyethylene 0.5 oleyl ether (20E, 0.) 2゜4■ Propylene glycol 5.0■ Disinfectant/preservative
Amount■ Ion exchange water
Remaining amount (manufacturing method) ■, ■, ■, ■, ■ at 75°C, ■, ■, ■ at 73°C
The oil phase is added to the aqueous phase while stirring to emulsify, and then cooled to 30'C to dissolve vitamin E.
A containing water-soluble agent was obtained.

Claims (3)

[Claims] (1) One or more fat-soluble vitamins and a water-soluble polyhydric alcohol having two or more hydroxyl groups in the molecule.
species or two or more species, and polyglycerin fatty acid ester,
A water-soluble agent containing fat-soluble vitamins containing ethanol and water. (2) The water-soluble agent containing fat-soluble vitamins according to claim 1, wherein the polyglycerin fatty acid ester has a degree of glycerin polymerization of 6 to 15. (3) The water-soluble agent containing fat-soluble vitamins according to claim 1, wherein the amount of ethanol is 0.5 to 20% by weight.