JP3417419B2 - External preparation for skin - Google Patents

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.

(Claim 1) That is, the gist of the present invention is to provide a stabilizer for external preparation for skin of vitamin A and / or its fatty acid ester consisting of cyclodextrin in which an antioxidant and / or an ultraviolet absorber is included. Exists. (Claim 2) That is, the gist of the present invention is claim 1.
The method for stabilizing an external preparation for skin is characterized by stabilizing vitamin A and / or a fatty acid ester thereof in the external preparation for skin using the stabilizer according to 1. (Claim 3) That is, the gist of the present invention is that the cyclodextrin is a lower alkylated cyclodextrin and / or a hydroxyalkylated cyclodextrin, and a vitamin A and / or a fatty acid ester thereof is different.
It exists in the stabilizer according to claim 1, which is used for stabilization against sexualization, decomposition and polymerization . Abstracts (claim 4) That is, the present invention provides a stabilization method of claim 2 wherein the cyclodextrin is a lower alkyl cyclodextrin and / or hydroxyalkylated cyclodextrin, vitamin in the skin external preparation
Which stabilizes A and / or its fatty acid ester
And a stabilizer for external preparation for skin according to claim 1
It is present in a skin external preparation characterized by: (Claim 5) That is, the gist of the present invention is that the antioxidant is butylhydroxytoluene (hereinafter abbreviated as BHT), butylhydroxyanisole (hereinafter abbreviated as BHA),
One or more oil-soluble antioxidants selected from the group consisting of α, β, γ, δ-tocopherol, nordihydroguaiaretin, propyl gallate, vitamin C fatty acid ester, and sorbic acid, and / or benzophenone-based UV light The external preparation for skin according to claim 4, which is one or more of an absorbent, a cinnamic acid ester-based ultraviolet absorbent, and a dibenzoylmethane-based ultraviolet absorbent.
Agent and / or UV absorber is cyclodextrin
Resistant to an aqueous solution (referred to as CD) (concentration of 20 to 60% by weight)
Oxidizing agent, UV absorber 0.01 to 0.2 for CD
Parts and stirred at 20-60 ° C. (50-3000 rp
m), with an inclusion compound that was included for approximately 2 to 12 hours
Existence in the external preparation for skin according to claim 4, characterized in that
To do. (Claim 6) That is, the gist of the present invention is cyclodex
Vitamin A you in inclusion to have a have a skin external agent in Trinh
And / or a stabilized fatty acid ester thereof
It is present in the external preparation for skin according to claim 5.

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 wt.

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.

[0018]

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 It was measured by an absorbance measuring method at 325 nm using ethanol. 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) = Absorption maximum 325 nm, E (1%, 1) in calculating absorbance of retinol
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.

Method for Quantifying Retinol Acetate According to Japanese Pharmacopoeia (11th revision) Vitamin A Quantitative Method 1st method, quantification was carried out by an absorbance measuring method using isopropanol.

[0027]   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 Amount of purified water as 100

[0028]   Example 6 Beauty Essence (wt%) HP-β-CD 30 BHT 1 Retinol acetate 5 Retinol palmitate 5 Isopropyl myristate 10 POE (60) hydrogenated castor oil 1 POE (20) sorbitan laurate 1 Carboxy vinyl polymer 0.3 Triethanolamine 2.3 Ethanol 3 Methylparaben 0.1 Amount of purified water as 100

[0029]   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 Amount of purified water as 100

[0030]   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 Amount of purified water as 100

[0031]   Example 9 Beauty powder (wt%) 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 100 is the amount   *: 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.

─────────────────────────────────────────────────── ─── Continued Front Page (51) Int.Cl. ⁷ Identification Code FI A61K 7/42 A61K 7/42 7/48 7/48 A61P 17/00 A61P 17/00 17/16 17/16

Claims (6)

(57) [Claims] 1. A stabilizer for external preparation for skin of vitamin A and / or its fatty acid ester comprising cyclodextrin in which an antioxidant and / or an ultraviolet absorber is included. 2. A method for stabilizing a skin external preparation, which comprises stabilizing the vitamin A and / or a fatty acid ester thereof in the skin external preparation by using the stabilizer according to claim 1 . 3. The cyclodextrin is a lower alkylated cyclodextrin and / or a hydroxyalkylated cyclodextrin, which is safe for isomerization, decomposition and polymerization of vitamin A and / or its fatty acid ester.
The stabilizer according to claim 1, which is used for normalization. 4. The stabilizing method according to claim 2, wherein the cyclodextrin is a lower alkylated cyclodextrin and / or a hydroxyalkylated cyclodextrin.
From vitamin A and / or its fat in the external preparation for skin
Outside the skin according to claim 1, for the purpose of stabilizing a fatty acid ester.
For external use on the skin, characterized by containing a stabilizer for an ointment
Agent. 5. The antioxidant is 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 external preparation for skin according to claim 4, which is one or more absorbents, wherein the antioxidant and / or the ultraviolet absorbent is used.
Aqueous solution of cyclodextrin (CD) (2
CD with antioxidant and UV absorber at 0-60 wt% concentration)
To 0.01 to 0.2 parts and stirred at 20 to 60 ° C
(50-3000 rpm) in about 2-12 hours
5. A clathrate compound that is clathrated.
The skin external preparation described. 6. Cyclodextrin-free inclusion
Vitamin A and / or its fatty acid in external preparation for skin
The skin according to claim 5, wherein the steal is stabilized.
Topical skin agent.