JPS5841813A - Emulsion external agent composition containing stably mixed vitamin a - Google Patents

Abstract

PURPOSE:The titled composition, containing vitamin A, an antioxidant, e.g. di- tert-butylhydroxytoluene, butylhydroxyanisole or tocopherol, and EDTA salt, and having a stabilizing effect on the vitamin A for a long term. CONSTITUTION:An emulsion skin external agent composition containing vitamin A, 0.001-0.5%, based on the total composition, antioxidant, e.g. di-tert-butylhydroxytoluene, butylhydroxyanisole or tocopherol, and 0.001-0.5% EDTA salt as an emulsion medicinal pharmaceutical, quasi-drug or cosmetic, e.g. an emulsion, cream, aerosol or pack. The use of the specific antioxidant and EDTA salt improves the stability of the vitamin A remarkably without causing the problem such as the coloring of the system. 0.01-0.5%, based on the total composition, vitamin A palmitate or acetate is used as the vitamin A.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to an emulsion-based skin external preparation composition stably containing vitamin A, more specifically, an emulsion-based skin external pharmaceutical preparation such as a cream or a milky lotion stably containing vitamin A; Regarding quasi-drugs and cosmetics.

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, but is extremely susceptible to oxidation and is known to be extremely unstable in the presence of water.

For this reason, vitamin A has traditionally been included in emulsified skin preparations, but vitamin A is extremely unstable due to the water present in the system, and is rapidly oxidized over time. It loses its efficacy, making it difficult to stably retain 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 system for external use on the skin has yet been found.

In view of these circumstances, the present inventors have conducted extensive studies on stabilizing vitamin A in emulsified skin preparations.

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 tried using various antioxidants, and combined antioxidants with synergists such as ultraphosphoric acid, citric acid, ascorbic acid, sorbitol, and various amino acids. However, on the contrary, significant coloration occurred in the system, which was thought to be derived from the oxidation products of vitamin A, the antioxidant, and the synergist itself, and no sufficiently satisfactory improvement in stability was observed. However, surprisingly, it was found that when a certain type of antioxidant is used in combination with ethylenediaminetetraacetate (hereinafter referred to as EDTA salt), the stability of vitamin A is significantly improved, and the problem of coloration of the system does not occur. did.

The present invention was completed based on such knowledge, and
In an emulsified skin external preparation composition containing vitamin A as an active ingredient, di-t-butylhydroxytoluene (hereinafter referred to as B
HT), butylhydroxyanisole (hereinafter referred to as B
The present invention provides an emulsified skin preparation composition stably containing vitamin A, which is characterized by containing an antioxidant selected from the group consisting of HA) and tocopherol, and EDTA salt. In the present invention, EDTA
Salt is also considered to be a kind of antioxidant synergist, but its mechanism of action is not clear, and unlike the conventionally used synergists mentioned above, it does not cause problems such as coloring of the system, and it can be used with vitamins and antioxidants. Oxidation of vitamin A can be effectively prevented and long-term stabilization of vitamin A contained in emulsified skin preparations can be achieved.

Next, the results of testing the stabilizing effects of various antioxidants and synergists on vitamin A blended into the emulsion are shown.

Test method Various emulsions containing vitamin A palmitate and various antioxidants and/or synergists were prepared according to the prescriptions described below, and after storage at 40°C for one month, the number of vitamin A units in each emulsion was determined. The residual rate (%) with respect to the initial number of vitamin A units was calculated. At the same time, the degree of coloring of the emulsion was visually evaluated.

Emulsion prescription ingredients Weight% Fragrance
Follow this recipe in an appropriate amount,
Each component was mixed and dissolved by heating at about 75°C, and this was added to the mixture of each component of B heated to about 75°C, stirred well, cooled, and then perfume was added to obtain an emulsion. .

Quantification of vitamin A palmitate was performed as follows.

Emulsion sample No. 109 was accurately weighed and dissolved in about 80 g of a chloroform-ethanol (1:1) mixture. This was filtered and diluted with the same mixture to make 100 d, which was used as a sample solution.

Separately, approximately 10 μm of a standard vitamin A palmitate product whose number of vitamin A units had been measured in advance was accurately weighed to prepare a chloroform-ethanol (1:1) mixed solution, which was used as a standard solution.

These sample solutions and standard solutions were each injected into a 20-loop measuring tube and subjected to high performance liquid chromatography (high performance liquid chromatography device Lc-1 manufactured by Shimadzu Corporation).
, Column: Nucleosil C-1C-18 (25φ4 m
), mobile phase: methanol, column temperature: 35°C, flow rate: 1. Oi/min, detection wavelength: 320 nm). Measure the peak height of vitamin A palmitate in the obtained chromatogram, set the peak height of the sample solution as A[, the peak height of the standard solution as As, and calculate the number of vitamin A units in the sample solution according to the following formula. I asked for it.

The results are shown in Table 1 below. As a control, the results of a similar test on a milky lotion without the addition of an antioxidant or synergist are also shown. Moreover, the coloring in Table 1 was evaluated according to the following criteria.

○: No coloring Todoroki: Slightly colored ×: Coloring ×X: Somewhat severe coloring XXX: Severe coloring xxxx: Very colored Table 1 Table 1 (pecking) Note) - Two combinations are not included.

As shown in Table 1, only when EDTA salts and antioxidants are used together can a high vitamin A residual rate of over 70% be maintained without coloring even after storage at 40°C for one month. can. Note that BHA also showed the same tendency as BHT.

Thus, the skin external preparation composition of the present invention is 0/W type, W2 type.
Any O-type emulsification system may be used, and vitamin A is blended as an active ingredient, and the above-mentioned antioxidant and EDTA salt are used in combination to stabilize the emulsion system.

The vitamin A used is vitamin A palmitate,
Vitamin A acetate, etc., may be used, and the amount to be added will depend on the dosage form of the actual composition,
It can be selected as appropriate depending on the desired medicinal effect, etc., but in general, it is 0.01 to 0.5% (by weight, the same applies hereinafter) based on the total amount of the composition.
degree is preferred.

The antioxidant may be BHT, BHA, or tocopherol, and as is clear from Table 1, BHT is preferred because it has a high stabilizing effect. There are various isomers of tocopherol, but in the present invention, they are not particularly limited, and may be either d, /, d/, α,
Either β, γ, or δ may be integrated. In addition, vitamin E, known as a mixture of these and tocopherols,
etc. can also be used. Note that combining tocopherol with other antioxidants will actually promote oxidation, so mixed use of such antioxidants should be avoided.

Although the amount of the antioxidant can be selected as appropriate, it is generally desirable to use an amount of about 0.001 to 0.5 with respect to the total amount of the composition.

As the EDTA salt, EDTA-1 sodium EDTA
-2-sodium, EDTA-3-sodium, EDTA-
4-sodium is used, and it is usually desirable to use it in an amount of about 0.001 to 0.5% based on the total amount of the composition.

The skin external preparation composition of the present invention can be prepared into pharmaceutical preparations, quasi-drugs, and cosmetics in the form of emulsions such as milky lotions, creams, aerosols, and packs according to conventional methods, and other ingredients. is not particularly limited, and may be any commonly used one. In particular, the oil phase components contain medium-chain triglycerides such as tricaprylic acid glyceride, tri(2-ethylhexanoic acid) glyceride, isopropylene monostearate, isopropyl monostearate, It has been found that adding a large amount of ester oils such as cetyl 2-ethylhexanoate and isopropyltumalmitatetonyl glycol has the effect of improving the stability of vitamin A and softening the lips. It is preferable to use this method.

Next, the present invention will be explained in more detail with reference to Examples.

Example 1 Nutritional Cream Ingredients Weight % Fragrance
According to this recipe, mix appropriate amounts of each component of A, heat and dissolve at about 75°C, and add about 75°C.
Add to the mixture of each component of R heated to 5°C, stir well,
The mixture was cooled and then flavoring was added to obtain a nutritional cream stably containing vitamin A.

Example 2 Emulsion ingredient Weight% fragrance
An emulsion containing a stable amount of vitamin A was obtained in the same manner as in Example 1 according to this prescription.

Example 3 Emulsion components Weight % F, DTA
-2su）+Jum 0.02Fragrance
An emulsion containing a stable amount of vitamin A was obtained in the same manner as in Example 1 according to this prescription.

Example 4 Cold Cream Ingredients Weight % Perfume Appropriate Amount This formulation was strained in the same manner as in Example 1 to obtain a cold cream containing vitamin A in a stable manner.

Patent applicant Sunstar Co., Ltd. Representative patent attorney Aoyama Ao + 9J) - 2 people

Claims (1)

[Claims] (1) A vitamin A-containing emulsified skin external preparation composition containing an antioxidant selected from the group consisting of di[-butylated hydroxytoluene, butylated hydroxyanisole, and tocopherol] and ethylenediaminetetraacetate. An emulsified skin external preparation composition stably containing A.