JPH0899827A - Skin external agent - Google Patents

Abstract

PURPOSE: To obtain a skin external agent improved in the stability of the α- tocopheryl retinoate and highly improved in its effect, formulated with an α- tocopheryl retinoate and a polar oil ingredient selected from pentaerythritol fatty acid esters and trimethylolpropane fatty acid esters. CONSTITUTION: This skin external agent contains pref. 0.001-10 (esp. 0.01-2.0) wt.% of an α-tocopheryl retinoate and pref. 0.1wt.% of a polar oil ingredient selected from pentaerythritol fatty acid esters and trimethylolpropane fatty acid esters and, preferably, 0.01-10wt.% of a liposoluble antioxidant such as butyl hydroxytoluene, butyl hydroxyanisole, α-, β-, γ-, δ-tocopherol, nordihydroguaiaretin, propyl gallate, vitamin C fatty acid ester or sorbic acid.

Description

Detailed Description of the Invention

[0001]

FIELD OF THE INVENTION The present invention relates to an external preparation for skin in which the stability of α-tocopheryl retinoate is improved and the effect thereof is remarkably improved.

[0002]

BACKGROUND OF THE INVENTION It is known that α-tocopheryl retinoate is an effective component for prevention and treatment of cutaneous keratoses, prevention of skin aging and recovery. Compounds used as pharmaceutical and cosmetic ingredients (Japanese Patent Publication No. 59-22684, Japanese Patent Publication No. 53-15429, and Japanese Patent Publication No. 54-84034).
JP-A No. 2-300123, etc.).

However, as is well known, α-
Tocopheryl retinoate is structurally extremely unstable and easily undergoes hydrolysis, various isomerizations and polymerization due to light, air, heat, metal ions, etc., resulting in a decrease in activity during storage. However, it was difficult to stably mix it with the external preparation for skin. Therefore, conventionally, attempts have been made to improve the storage stability of α-tocopheryl retinoate. For example, an antioxidant such as ascorbic acid or tocopherol may be allowed to coexist (see JP-A-2- 300
123) and coexistence of carotenoids to enhance stability against light etc. (Japanese Patent Laid-Open No. 163143/1993).
No. publication) is known. However, the former method of coexisting antioxidants is insufficient in its stabilizing effect, and the latter method of adding carotenoids has
Even if the compounding amount is about 01% by weight, the base is colored, and if it is tried to mix the necessary amount for obtaining the desired stabilizing effect, it cannot avoid a considerable amount of coloring, and is excessive in the nature as an external preparation for skin. Considering that coloring should be avoided,
There is a problem that a large amount of carotenoid cannot be blended. A satisfactory method for stabilizing α-tocopheryl retinoate has not yet been found, and development of an excellent stabilizing means is desired.

[0004]

DISCLOSURE OF THE INVENTION As a result of earnest research in view of such circumstances, the present inventors have found that a polar oil component selected from the group consisting of pentaerythritol fatty acid ester and trimethylolpropane fatty acid ester together with α-tocopheryl retinoate. If one or more of
-It was found that the stability of tocopheryl retinoate is improved, and one or more polar oil components selected from the group consisting of pentaerythritol fatty acid ester and trimethylolpropane fatty acid ester together with α-tocopheryl retinoate. And butylhydroxytoluene, butylhydroxyanisole, α, β,
γ, δ-tocopherol, nordihydroguaiaretin,
It was found that the stability of α-tocopheryl retinoate is remarkably improved by blending with propyl gallate, vitamin C fatty acid ester, and one or more oil-soluble antioxidants selected from the group consisting of sorbic acid, The present invention has been completed. That is, the gist of the present invention is to blend one or more polar oil components selected from the group consisting of α-tocopheryl retinoate, pentaerythritol fatty acid ester, and trimethylolpropane fatty acid ester, preferably α- One or more polar oil components selected from the group consisting of tocopheryl retinoate, pentaerythritol fatty acid ester, and trimethylolpropane fatty acid ester, butyl hydroxytoluene (hereinafter abbreviated as BHT), and butyl hydroxyanisole (hereinafter Abbreviated as BHA), α,
One or two or more oil-soluble antioxidants selected from the group consisting of β, γ, δ-tocopherol, nordihydroguaiaretin, propyl gallate, vitamin C fatty acid ester, and sorbic acid. Present in topical skin preparations.

The structure of the present invention will be described in detail below. The α-tocopheryl retinoate used in the present invention means α
An ester of tocopherol and vitamin A acid, α
-Tocopheryl retinoate is a natural mixed tocopherol containing DL-α-tocopherol, D-α-tocopherol or D-α-tocopherol, and vitamin A acid is retinoic acid, that is, all-trans-retinoic acid, 13- cis-retinoic acid, 11-cis-retinoic acid,
9-cis-retinoic acid or mixed isomers containing them. Among them, DL-α-tocopherol and all-tran
Most preferred is the ester of s-retinoic acid.

Α blended in the external preparation for skin according to the present invention
-The amount of tocopheryl retinoate is not particularly limited, but considering the effect of α-tocopheryl retinoate on the skin, it is 0.0001% by weight or more, and the effect of α-tocopheryl retinoate is strongly appealed. In order to achieve this, the content is preferably 0.001% by weight, more preferably 0.1%.
It is at least 01% by weight. The upper limit of compounding is 10% by weight or less, preferably 5.0% by weight, due to its properties as a skin external preparation.
Up to 2.0% by weight, more preferably up to 2.0% by weight.

The polar oil used in the present invention includes pentaerythritol fatty acid ester, preferably pentaerythritol fatty acid ester having 6 to 12 carbon atoms, and trimethylolpropane fatty acid ester, preferably trimethylolpropane fatty acid having 6 to 12 carbon atoms. A polar oil selected from the group consisting of esters, specifically, pentaerythritol-tetra (2-ethylhexanoic acid) ester and pentaerythritol-tetracaprylic acid ester are used as pentaerythritol fatty acid ester, and trimethylpropane Examples of the fatty acid ester include trimethylolpropane-tri (2-ethylhexanoic acid) ester and trimethylolpropane-tricapric acid ester.

The amount of pentaerythritol fatty acid ester and / or trimethylpropane fatty acid ester to be blended in the external preparation for skin of the present invention is not particularly limited because it varies widely depending on the external preparation formulation for skin. When the amount is extremely small, the α-tocopheryl retinoate or the oil-soluble antioxidant cannot be dissolved, and the effect of the present invention cannot be sufficiently exhibited. Therefore, α-tocopheryl retinoate or α-
The amount is preferably more than the sum of the amounts of tocopheryl retinoate and oil-soluble antioxidant, and 0.002% by weight.
As described above, it is preferably 0.1% by weight or more. The upper limit of blending varies widely depending on the dosage form of the external preparation for skin, but is not particularly limited, but the amount of α-tocopheryl retinoate or α-tocopheryl retinoate and the oil-soluble antioxidant according to the present invention is reduced from the total amount of the external preparation for skin. The upper limit is the amount.

Oil-soluble antioxidants to be added to the external preparation for skin of the present invention include butylhydroxytoluene, butylhydroxyanisole, α, β, γ, δ-tocopherols, nordihydroguaiaretin, gallic acid. Examples include propyl, vitamin C fatty acid ester, sorbic acid and the like.

The blending amount is 0.001% by weight or more, preferably 0.005% by weight or more. In order to exert the effect of the invention for a longer period, 0.01% by weight
The above is suitable. The upper limit is not particularly limited in view of the effect of the invention, but if the amount is extremely large, the quality as an external preparation for the skin may be impaired due to the precipitation of crystals and the like, so be careful, preferably 10% by weight.

The external preparation for skin of the present invention contains, in addition to the above-mentioned essential components, other components usually used in cosmetics and quasi drugs, such as moisturizers, surfactants, preservatives, water and alcohol. , Thickeners, other oils, drugs, chelating agents, fragrances, coloring agents, ultraviolet absorbers, etc. can be added, if necessary, within a range that does not impair the effects of the present invention.

[0012]

EXAMPLES The present invention will now be described in more detail by way of examples, which should not be construed as limiting the invention.
In addition, the compounding amounts in the examples and comparative examples are all wt%.

With the manufacturing method of Examples 1 to 3 and Comparative Examples 1 and 2,
Temperature test method Pentaerythritol fatty acid ester and / or trimethylpropane fatty acid ester are completely dissolved in each oil component at 60 ° C, and then cooled to 40 ° C. Then, α-tocopheryl retinoate is completely dissolved, sealed in a brown glass sample tube, and stored in a constant temperature bath at 40 ° C.

[0014]

[Table 1]

Quantitative method of α-tocopheryl retinoate The amount of α-tocopheryl retinoate was quantified by reverse phase high performance liquid chromatography using a UV detector.

In Examples 1, 2 and 3, α-
Tocopheryl retinoate has improved stability,
This is the effect according to the present invention.

Production methods of Examples 4 and 5 and Comparative Examples 3 and 4
Temperature test method Butyl hydroxytoluene and tocopherol are completely dissolved in each oil component at 60 ° C, and then cooled to 40 ° C.
Then completely dissolve α-tocopheryl retinoate,
It is sealed in a brown glass sample tube and stored in a constant temperature bath at 40 ° C.

[0018]

[Table 2]

Quantitative method of α-tocopheryl retinoate Quantitative determination was carried out by reverse phase high performance liquid chromatography using a UV detector.

In Examples 4 and 5, the stability of α-tocopheryl retinoate was improved as compared with Comparative Examples, which is an effect according to the present invention.

The production method of Examples 6 and 7 and Comparative Examples 5 and 6
Temperature test method Butylhydroxytoluene, tocopherol, each oily component and the surfactant are completely dissolved at 70 ° C., and immediately before emulsification, α-tocopheryl retinoate is completely dissolved to form an oil phase. Glycerin, propylene glycol, carboxyvinyl polymer, caustic potash are completely dissolved in purified water to 70
The oil phase is added to the aqueous phase heated to ℃ and emulsified by a homomixer type emulsifier. Next, a heat exchanger is used to cool the mixture to 30 ° C. to obtain an emulsion. The emulsion is filled in a metal-coated glass bottle, sealed, and stored in a constant temperature bath at 40 ° C.

[0022]

[Table 3]

In Examples 6 and 7, the stability of α-tocopheryl retinoate is improved as compared with Comparative Examples, which is an effect according to the present invention.

Quantitative method of α-tocopheryl retinoate Quantitative determination was carried out by reverse phase high performance liquid chromatography using a UV detector.

Example 8 Lotion (wt%) Pentaerythritol tetracapric acid ester 0.002 δ-tocopherol 0.001 α-tocopherol 0.0005 α-tocopheryl retinoate 0.0001 POE (50) oleyl ether 0.7 Lactic acid 0.1 Sodium lactate 0.9 Ethanol 5 Glycerin 1 Methylparaben 0.2 Trisodium edetate 0.01 Purified water Amount based on 100 as a whole

Example 9 Oil Essence (wt%) Pentaerythritol tetra (2-ethylhexanoic acid) ester 60 Trimethylolpropane tricapric acid ester 20 Squalane 10 BHT 1 α-tocopherol 4 α-tocopheryl retinoate 5

Example 10 Cream (wt%) 2-Ethylhexanoic acid triglyceride 10 Pentaerythritol tetra (2-ethylhexanoic acid) ester 15 BHT 0.05 BHA 0.01 α-tocopherol 0.01 α-tocopheryl retinoe -To 0.3 Vaseline 2 Squalane 8 Butylparaben 0.1 Propylparaben 0.1 Oleic acid monoglyceride 3 Diglycerin diisostearate 2 PEG400 Dioleate 1 Glycerin 10 Dipropylene glycol 5 Purified water 100 parts

Example 11 Irinkle oil (% by weight) Pentaerythritol tetra (2-ethylhexanoic acid) ester 40 Trimethylolpropane tricapric acid ester 20 2-Ethylhexanoic acid triglyceride 20 Squalane 19 α-tocopheryl retinoate 1

Example 12 Lotion (wt%) Pentaerythritol tetracapric acid ester 0.002 δ-tocopherol 0.001 Tocoretinate 0.0001 POE (50) oleyl ether 0.7 Lactic acid 0.1 Sodium lactate 0.9 Ethanol 5 Glycerin 1 Methylparaben 0.2 Trisodium edetate 0.01 Purified water Amount based on 100 as a whole

Example 13 Oil Essence (wt%) Pentaerythritol tetra (2-ethylhexanoic acid) ester 60 Trimethylolpropane tricapric acid ester 10 Squalane 10 BHT 1 α-tocopherol 9 α-tocopheryl retinoate 10

The external preparations for skin of Examples 8 to 13 were excellent in the stability of α-tocopheryl retinoate in daily use.

[0032]

In the external preparation for skin of the present invention, one or more polar oil components selected from the group consisting of pentaerythritol fatty acid ester and trimethylolpropane fatty acid ester are blended to form α-tocopheryl retinoe. -The stability of the gating can be improved. Further, preferably, together with α-tocopheryl retinoate, pentaerythritol fatty acid ester, and one or more polar oil components selected from the group consisting of trimethylolpropane fatty acid ester, and butylhydroxytoluene, butylhydroxyanisole, α,
By blending one or more oil-soluble antioxidants selected from the group consisting of β, γ, δ-tocopherol, nordihydroguaiaretin, propyl gallate, vitamin C fatty acid ester, and sorbic acid, α-tocopherol The stability of ferryl retinoate can be significantly improved.

─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. ⁶ Identification code Internal reference number FI technical display location A61K 47 / 22K

Claims (3)

[Claims] 1. An external preparation for skin, which comprises blending α-tocopheryl retinoate and one or more polar oil components selected from the group consisting of pentaerythritol fatty acid ester and trimethylolpropane fatty acid ester. 2. The external preparation for skin according to claim 1, which further comprises an oil-soluble antioxidant. 3. The oil-soluble antioxidant is butylhydroxytoluene, butylhydroxyanisole, α, β, γ, δ.
The external preparation for skin according to claim 2, which is one or more selected from tocopherol, nordihydroguaiaretin, propyl gallate, vitamin C fatty acid ester, and sorbic acid.