JPH0244806B2 - BITAMINAOANTEINIHAIGOSHITANYUKAKEIHIFUGAIYOZAISOSEIBUTSU - Google Patents

Description

[Detailed description of the invention]

The present invention relates to emulsified external skin preparation compositions containing vitamin A in a stable manner, and more particularly to emulsified pharmaceutical preparations for external use on the skin such as creams and emulsions, quasi-drugs, and cosmetics containing vitamin A in a stable manner. . Conventionally, various vitamins have been used as active ingredients in external skin preparations, and vitamin A is also known to be an effective ingredient in the prevention and treatment of skin keratosis and the like. On the other hand, vitamin A, which is a fat-soluble vitamin, is relatively stable in the absence of water;
It is known to be extremely susceptible to oxidation and extremely unstable in the presence of water. Therefore, vitamin A has traditionally been included in emulsified skin preparations;
Vitamin A is extremely unstable due to the water present in the system, and rapidly oxidizes and loses its effectiveness over time, making it difficult to stably maintain vitamin A in the system over a long period of time. However, the stabilization of vitamin A in such an emulsion system has not been studied much in the past, and no effective means for stably incorporating vitamin A into an emulsion-based skin preparation for external use has yet been found. It has been proposed to stabilize vitamin A in the emulsification system by blending a high-molecular polysaccharide such as xanthan gum (Japanese Patent Laid-Open No. 50-82223).
(No.), the effect of the combination of high-molecular polysaccharides on the feel of the product is a problem. In view of these circumstances, the present inventors have conducted extensive studies on stabilizing vitamin A in emulsified external skin preparations that do not contain polymeric polysaccharides. First, various studies were conducted to stabilize the product by changing the method of blending vitamin A, but no improvement in stability was observed. Next, in order to prevent the oxidation of vitamin A,
We have tried using various antioxidants and combining antioxidants with synergists such as ultraphosphoric acid, citric acid, ascorbic acid, sorbitol, and various amino acids, but on the contrary, vitamin A
Significant coloring of the system occurred, which was thought to be due to the oxidation products of the compound, the antioxidant, and the synergist itself, and no sufficiently satisfactory improvement in stability was observed. However, surprisingly, when using tocopherol as an antioxidant, the stability of vitamin A is significantly improved when ethylenediaminetetraacetate (hereinafter referred to as EDTA salt) and a specific liquid ester oil are used together, and the coloring of the system is significantly improved. It turns out that this problem does not arise. The present invention has been completed based on this knowledge, and provides vitamin A that does not contain polymeric polysaccharides.
In the emulsified skin external preparation composition containing as active ingredients, tocopherol and EDTA salt, tricaprylic acid glyceride, tri(2-ethylhexanoic acid) glyceride, cetyl 2-ethylhexanoate, and di-(2-ethylhexanoic acid) To provide an emulsified skin external preparation composition that is stably blended with vitamin A and is free of polymeric polysaccharides, characterized in that it contains an ester oil selected from the group consisting of neopentyl glycol. In the present invention,
EDTA salt is also considered to be a type of antioxidant synergist, but its mechanism of action is not clear.Unlike the conventionally used synergists mentioned above, it does not cause problems such as coloring of the system, and it is effective against vitamin A along with tocopherol. It is possible to effectively prevent the oxidation of vitamin A and achieve long-term stabilization of vitamin A contained in emulsified skin preparations. Next, the results of testing the stabilizing effects of various tocopherols and synergists on vitamin A blended into emulsion are shown. Test method Various emulsions containing vitamin A palmitate and various tocopherols and/or sinergists were prepared according to the formulations below, and the emulsions were heated at 40℃ for 1
After storage for several months, the number of vitamin A units in each emulsion was determined, and the residual rate (%) relative to the initial number of vitamin A units was calculated. At the same time, the degree of coloring of the emulsion was visually evaluated.

[Table] Water = Remainder
Fragrance (appropriate amount)
According to this recipe, mix each component of A at about 75℃.
This was added to the mixture of each component of B heated to about 75°C, stirred well, cooled, and then a fragrance was added to obtain a milky lotion. Quantification of vitamin A palmitate was carried out as follows. Approximately 10 g of the emulsion sample was accurately weighed and dissolved in approximately 80 ml of a chloroform-ethanol (1:1) mixture. This was filtered, diluted with the same mixture to make 100 ml, and used as a sample solution. Separately, accurately weigh out approximately 10 mg of a standard vitamin A palmitate product whose number of vitamin A units has been measured in advance.
100 with chloroform-ethanol (1:1) mixture
ml, and this was used as a standard solution. These sample solutions and standard solutions, respectively,
It was injected into a 20 μ loop measuring tube and subjected to high performance liquid chromatography (Shimadzu Corporation, high performance liquid chromatography device LC-1, column: Nucleosil C-18 (28 cm x φ4 mm), mobile phase: methanol, column temperature. : 35℃, flow rate: 1.0ml/min, detection wavelength:
320nm). Measure the peak height of vitamin A palmitate in the obtained chromatogram, and define the peak height of the sample solution as At and the peak height of the standard solution as As.
The number of vitamin A units in the sample solution was determined according to the following formula. Number of vitamin units in the sample solution = Number of units in 1 g of vitamin A palmitate standard product × Weighed amount of vitamin A palmitate standard product mg × 1/1000
×At/As The results are shown in Table 1 below. In addition, as a control, the results of a similar test on an emulsion without tocopherol or synergist are also shown. Moreover, the coloring in Table 1 was evaluated according to the following criteria. ○: Not colored △: Slightly colored ×: Colored ××: Slightly colored ×××: Severely colored ××××: Very colored

【table】

[Table] As shown in Table 1, only when EDTA salt and tocopherol are used together, a high vitamin A residual rate of over 70% can be maintained without coloring even after storage at 40℃ for one month. can. In addition, the above emulsion formula contains natural vitamin E or δ-tocopherol 0.05%, EDTA/2Na 0.02
% and isopropyl myristate
The vitamin A residual rate (%) and coloring of emulsions prepared by adding various oil and fat components instead of 1.0% were similarly evaluated. The results are shown in Tables 2 and 3.

【table】

【table】

【table】

[Table] As shown in Tables 2 and 3, when the above-mentioned ester oil is used in combination, vitamin A is significantly stabilized. Thus, the skin external preparation composition of the present invention is O/W.
Either type or W/O type emulsification system may be used, and vitamin A is blended as an active ingredient, and stabilization is attempted by combining tocopherol and EDTA salt and blending the ester oil into the oil phase. The vitamin A to be used may be any of those commonly incorporated into this type of composition, such as vitamin A palmitate and vitamin A acetate, and the amount to be added can be selected as appropriate depending on the actual dosage form of the composition, desired medicinal efficacy, etc. , generally 0.01 based on the total composition
It is preferably about 0.5% (weight %, the same applies hereinafter). There are various isomers of tocopherols, but in the present invention, they are not particularly limited, and include d,
Either l or dl-forms may be used, and α, β, γ,
Any δ-isomer may be used. Furthermore, mixtures of these and vitamin E, which is known as a mixture of tocopherols, can also be used. Note that combining tocopherols with other antioxidants will actually promote oxidation, so mixed use of such antioxidants should be avoided. Although the amount of tocopherol to be added can be selected as appropriate, it is generally desired to be about 0.001 to 0.5% based on the total amount of the composition. EDTA salts include EDTA-1 sodium,
EDTA-disodium, EDTA-trisodium,
EDTA-4 sodium etc. are used, and usually
It is preferably about 0.001 to 0.5% based on the total amount of the composition. The ester oil is usually used in an amount up to about 20%, and may be used in a larger amount, but the second
As is clear from the table and Table 3, no further improvement in the stabilizing effect of vitamin A can be expected. The skin external preparation composition of the present invention can be prepared according to a conventional method.
It can be prepared into pharmaceutical preparations, quasi-drugs, and cosmetics in the form of emulsions such as emulsions, creams, aerosols, and packs, and other ingredients are not particularly limited, and any commonly used ingredients can be used. good. Next, the present invention will be explained in more detail with reference to Examples. Example 1

[Table] Appropriate amount of fragrance
According to this recipe, mix each component of A at about 75℃.
This was added to the mixture of each component of B heated to about 75° C., stirred well, cooled, and then a fragrance was added to obtain an emulsion in which vitamin A was stably blended. Example 2

[Table] Appropriate amount of fragrance
According to this formulation, a cold cream stably containing vitamin A was obtained in the same manner as in Example 1 above.

Claims (1)

[Claims] 1. In a vitamin A-containing external skin preparation composition containing no polymeric polysaccharide, tocopherol and ethylenediaminetetraacetate, tricaprylic acid glyceride, tri(2-ethylhexanoic acid)
Contains an ester oil selected from the group consisting of glyceride, cetyl 2-ethylhexanoate, and neopentyl di-(2-ethylhexanoate) Glyceride Stable blend of vitamin A, free of polymeric polysaccharides Emulsified skin external preparation composition.