JPH0632715A - External preparation for skin - Google Patents

Abstract

PURPOSE:To obtain an external preparation for skin remarkably improved in stability of vitamin A and/or its fatty acid ester. CONSTITUTION:This external preparation for skin is obtained by blending vitamin A and/or its fatty acid ester with one or two or more kinds of cyclodextrins clathrating one or two or more kinds of antioxidants and/or ultraviolet rays absorbing agents. As the antioxidants, lipophilic antioxidants selected from a group consisting of butylhydroxytoluene, butylhydroxyanisol, alpha,beta,gamma,delta-tocopherol, nordihydroguaiareticacied, propyl gallate, vitamin C fatty acid esters and sorbic acid are used.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an external preparation for skin in which the stability of vitamin A and / or its fatty acid ester is improved and the effect thereof is remarkably improved.

[0002]

2. Description of the Related Art Vitamin A and / or its fatty acid ester is known to be an effective component for the prevention and treatment of cutaneous keratoses and the prevention and recovery of skin aging.

However, vitamin A and / or its fatty acid ester is structurally extremely unstable, and light,
Since various isomerizations, decompositions, polymerizations, etc. are easily caused by air, heat, metal ions, etc., it has been difficult to stably compound them in the skin external preparation.

[0004]

DISCLOSURE OF INVENTION Problems to be Solved by the Invention As a result of intensive studies in view of such circumstances, the present inventors have found that vitamin A and / or its fatty acid ester, vitamin A and / or its fatty acid ester, an antioxidant and / or an ultraviolet ray. It has been found that the stability of vitamin A and / or its fatty acid ester is significantly improved by incorporating cyclodextrin in which an absorbent is included, and the present invention has been completed.

[0005]

[Means for Solving the Problems]

(Claim 1) That is, the gist of the present invention is to a skin external preparation characterized in that a cyclodextrin including an antioxidant and / or an ultraviolet absorber is mixed with vitamin A and / or its fatty acid ester. Exists. (Claim 2) That is, the gist of the present invention is to provide a lower alkylated cyclodextrin and / or a hydroxyalkylated cyclodextrin in which an antioxidant and / or an ultraviolet absorber is included together with vitamin A and / or a fatty acid ester thereof. It exists in a skin external preparation characterized by being blended. (Claim 3) That is, the gist of the present invention is butylhydroxytoluene (hereinafter abbreviated as BHT), butylhydroxyanisole (hereinafter abbreviated as BHA), α, β, together with vitamin A and / or its fatty acid ester. γ,
δ-tocopherol, nordihydroguaiaretin, propyl gallate, vitamin C fatty acid ester, one or more oil-soluble antioxidants selected from the group consisting of sorbic acid and / or benzophenone ultraviolet absorber,
A cinnamic acid ester-based ultraviolet absorber and a dibenzoylmethane-based ultraviolet absorber are contained in a skin external preparation characterized by being mixed with cyclodextrin including one or more of them.

The structure of the present invention will be described in detail below.

Vitamin A and / or used in the present invention
Alternatively, as the fatty acid ester thereof, vitamin A (also known as retinol), vitamin A acetate (also known as retinol acetate), and vitamin A palmitate (also known as retinol palmitate) are exemplified, and a11-trans type or 13-cis It is preferably a mold and may be a mixture thereof. Further included are fatty oils obtained from fresh aquatic animals liver and pyloric appendix, and concentrates thereof.

There is no particular limitation on the amount to be added to the skin external preparation according to the present invention, but considering the effect of vitamin A on the skin, it is 0.0001% by weight or more, and the effect of vitamin A is strongly appealed. In order to
It is 1% by weight or more. The upper limit of the compounding ratio is preferably 10% by weight in view of the property as an external preparation for skin.

The cyclodextrin (hereinafter abbreviated as CD) used in the present invention is a cyclic oligosaccharide, and has a structure of α, β and γ depending on the difference in the number of glycoses.
(Hereinafter simply abbreviated as α-CD, β-CD, γ-CD) or methyl C into which a lower alkyl group is introduced.
D (hereinafter simply referred to as M-CD), ethyl CD (hereinafter simply referred to as E-CD), hydroxyalkylated hydroxymethyl CD (hereinafter simply referred to as HM-CD), hydroxyethyl CD ( Hereafter simply HE-CD
Is omitted. ), Hydroxypropyl CD (hereinafter simply H
Abbreviated as P-CD. ), Hydroxybutyl CD (hereinafter simply abbreviated as HB-CD), and the like.

Among them, α-CD and γ-CD have good solubility in water, but the yield by the method of decomposing starch is low and the cost is somewhat unsatisfactory. Although β-CD is advantageous in terms of cost, its solubility is somewhat unsatisfactory. In any case, the effects of the present invention can be sufficiently obtained if the respective properties are well known and utilized.

On the other hand, methylated CD and hydroxyalkylated CD are preferable, especially methyl-β-C, in view of their versatility in external preparations for skin, which have excellent solubility and cost.
D, hydroxyalkyl-β-CD is most suitable.

The amount of each CD to be added to the external preparation for skin according to the present invention is required to be 0.01% by weight or more, and the upper limit is not particularly limited in view of the effect of the present invention, but it is added in a remarkably large amount. In this case, although the effects of the present invention are not affected, the quality of the external preparation for skin may be impaired by the precipitation of crystals. It is preferably 10% by weight or less for α and γ-CD, 1% by weight or less for β-CD, and 30 for lower alkylated CD and hydroxyalkylated CD.
It is less than or equal to weight%.

The oil-soluble antioxidants to be added to the external preparation for skin according to the present invention include nordihydroguaiaretin and B.
Examples include HT, BHA, α, β, γ, δ-tocopherols, propyl gallate, vitamin C fatty acid ester, sorbic acid, and the like. Among them, BHT, BHA, α, β,
γ, δ-tocopherols are preferred.

The amount applied to the present invention is 0.001
It is preferably at least wt%, more preferably at least 0.01 wt%. In order to exert the effects of the invention for a longer period, 0.03% by weight is preferable. The upper limit of blending differs depending on the dosage form of the external preparation for skin and cannot be limited because it can be arbitrarily blended, but it is preferably 1% by weight from the nature of the external preparation for skin.

As the ultraviolet absorber used in the present invention, a benzophenone compound represented by 2-hydroxy-4-methoxybenzophenone, octylmethoxycinnamate, mono / di (methoxycinnamyl) -mono /
Cinnamic acid compounds represented by dioctyl glyceride,
Salicylic acid compounds represented by octyl salicylate,
Examples thereof include benzoic acid compounds represented by octyl paraaminobenzoate and dibenzoylmethane compounds represented by 4-t-butyl-4′methoxydibenzoylmethane. Preferred are benzophenone type, cinnamic acid type, and dibenzoylmethane type.

The amount applied to the present invention is 0.001
It is preferably at least wt%, more preferably at least 0.01 wt%. In order to exert the effects of the invention for a longer period, 0.03% by weight is preferable. The upper limit of blending differs depending on the dosage form of the external preparation for skin and cannot be limited because it can be arbitrarily blended, but it is preferably 1% by weight from the nature of the external preparation for skin.

As a method of encapsulating the above-mentioned CDs with an antioxidant and an ultraviolet absorber, generally, an antioxidant and an ultraviolet absorber are added to an aqueous solution of CDs (concentration of 20 to 60% by weight). To 0.01 to 0.2 parts of the above and stirred at 20 to 60 ° C. (50 to 3000 rpm) to obtain an inclusion compound in about 2 to 12 hours. The clathrate compound thus obtained is in a solubilized or emulsified state in an aqueous solution, and can be applied as it is to an external preparation for the skin, or the solution can be isolated as a powder by a method such as freeze-drying or spray-drying. It is possible.

It is also possible to mix the CDs, the antioxidant, and the ultraviolet absorber individually into the external preparation for skin and to include them all at once in the external preparation for skin.

In addition to the above-mentioned essential components, the external preparation for skin of the present invention contains other components usually used in cosmetics and quasi drugs, such as moisturizers, surfactants, preservatives, water, alcohols, thickeners, Other oils, drugs, chelating agents, fragrances, coloring agents,
Etc. can be blended as needed.

[0020]

EXAMPLES The present invention will now be described in more detail by way of examples, which should not be construed as limiting the invention.

[0021]

[Table 1]

The stability of retinol is improved as compared with Examples 1 and 2 and Comparative Example, which is an effect according to the present invention.

Quantitative Method for Retinol Using ethanol, the retinol was measured by an absorbance measuring method at 325 nm. For Example 2 and Comparative Example 2, samples were prepared by removing retinol from each, and the absorption at 325 nm was measured and corrected as the absorbance of the base. (Absorbance at 325 nm of samples of Examples and Comparative Examples)-(Absorbance of withdrawn product) = Absorbance of retinol Absorption maximum 325 nm, E (1%, 1)
cm) = 1835.

[0024]

[Table 2]

In Examples 3 and 4, the stability of retinol acetate is improved as compared with Comparative Example, which is an effect according to the present invention.

Quantitative Method of Retinol Acetate Japanese Pharmacopoeia (11th revision) Vitamin A quantitative method According to the first method, quantitative determination was carried out by an absorbance measuring method using isopropanol.

Example 5 Lotion (% by weight) Oleyl alcohol 0.002 β-CD 0.01 BHA 0.001 retinol acetate 0.0001 POE (50) oleyl ether 0.7 lactic acid 0.01 sodium lactate 0.09 Ethanol 5 Glycerin 1 Methylparaben 0.2 Purified water Amount based on 100 as a whole

Example 6 Beauty Essence (wt%) HP-β-CD 30 BHT 1 Retinol Acetate 5 Retinol Palmitate 5 Isopropyl myristate 10 POE (60) Castor Oil 1 POE (20) Sorbitan Laurate 1 Carboxyvinyl Polymer 0.3 Triethanolamine 2.3 Ethanol 3 Methylparaben 0.1 Purified water Amount based on 100 as a whole

Example 7 Cream (wt%) HE-β-CD 3 BHT 0.01 2-Hydroxy-4-methoxybenzophenone 0.02 Retinol 0.3 2-Ethylhexanoic acid triglyceride 10 Vaseline 2 Squalane 18 Butylparaben 0.1 Propylparaben 0.1 Oleic acid monoglyceride 3 Diglycerin diisostearate 2 PEG400 Dioleate 1 Glycerin 10 Dipropylene glycol 5 Purified water Amount based on 100 as a whole

Example 8 Lotion (% by weight) Retinol acetate 0.001 BHT inclusion-β-HPCD 5 (BHT: β-HPCD = 1: 100) Glycerin 2 citric acid 0.03 trisodium citrate 0.07 Ethanol 5 Methylparaben 0.1 Purified water 100%

Example 9 Beauty powder (% by weight) Retinol palmitate 0.3 α-tocopherol inclusion-α-CD 10 (α-tocopherol: α-CD = 1: 150) UV absorber inclusion-β-HPCD * 30 (UV absorber: β-HPCD = 1: 150) D-mannite based on 100 as a whole *: UV absorber: octyl methoxycinnamate

The skin external preparations of Examples 5 to 9 were excellent in stability of vitamin A and / or its fatty acid ester in daily use.

[0033]

In the external preparation for skin according to claim 1 of the present invention, the stability of vitamin A and / or its fatty acid ester can be improved by incorporating cyclodextrin including an antioxidant and / or an ultraviolet absorber. It can be significantly improved. In the external preparation for skin according to claim 2 of the present invention, vitamin A and / or the vitamin A and / or the same can be prepared by incorporating a lower alkylated cyclodextrin and / or a hydroxyalkylated cyclodextrin in which an antioxidant and / or an ultraviolet absorber is included. The stability of the fatty acid ester can be significantly improved. In the external skin preparation according to claim 3 of the present invention, butylhydroxytoluene (hereinafter abbreviated as BHT), butylhydroxyanisole (hereinafter abbreviated as BHA), α, β, γ, δ-tocopherol, nordihydroguaia. One or more oil-soluble antioxidants selected from the group consisting of retin, propyl gallate, vitamin C fatty acid ester, and sorbic acid, and / or benzophenone-based UV absorbers, cinnamic ester-based UV absorbers, dibenzoyl Stability of vitamin A and / or its fatty acid ester can be remarkably improved by incorporating cyclodextrin in which one or more methane type ultraviolet absorbers are included.

─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. ⁵ Identification code Internal reference number FI Technical display location A61K 7/42 7252-4C 7/48 9051-4C

Claims (3)

[Claims] 1. An external preparation for skin, characterized in that, together with vitamin A and / or a fatty acid ester thereof, cyclodextrin in which an antioxidant and / or an ultraviolet absorber is included. 2. The external preparation for skin according to claim 1, wherein the cyclodextrin is a lower alkylated cyclodextrin and / or a hydroxyalkylated cyclodextrin. 3. Antioxidants include butylhydroxytoluene (hereinafter abbreviated as BHT), butylhydroxyanisole (hereinafter abbreviated as BHA), α, β, γ, δ-tocopherol, nordihydroguaiaretin, gallic. One or more of oil-soluble antioxidants selected from the group consisting of acid propyl, vitamin C fatty acid ester, and sorbic acid, and / or benzophenone-based UV absorbers, cinnamic ester-based UV absorbers, dibenzoylmethane-based UV absorbers The skin external preparation according to claim 1, which is one or more kinds of absorbents.