JP2000026270A - Skin preparation for external use containing retinoids - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain the subject external preparation capable of improving stability of retinoids and maintaining the effectiveness of product for a long period of time by including a retinoid, a vitamin E and an amino sugar as essential components. SOLUTION: This skin preparation comprises (A) a retinoid (a compound showing vitamin A activity, the generic name of a compound working finally in an organism as a retinoic acid composite linked to a binding protein, such as various isomers of retinoic acid, etc.), (B) a vitamin E (the generic name of various compounds 2-methyl-6-chromanol structure having essential qualities as a radical scavenger such as α-tocopherol, etc.), and (C) an amino sugar (the generic name of a monosaccharide having a structure of formula I, formula II or formula III, a polysaccharide, a glycolipid, etc., and their derivatives such as glycosaminoglycan, etc.), as essential components. Preferably the amount of the composition A is, in the case of retinoic acid, 0.0001-2 wt.%, that of the component B is 0.001-10 wt.% and that of that of the component C is 0.001-20 wt.% based on the skin preparation.

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 containing retinoids, wherein the chemical stability of the retinoids is remarkably improved and the effectiveness as a product is maintained for a long period of time. It is.

[0002]

2. Description of the Related Art Retinoids are involved in the regulation of gene expression and are effective components for the prevention and treatment of skin photoaging, photopigmentation, skin carcinogenesis, cutaneous keratosis, dandruff, psoriasis and acne. However, it has not been possible to establish a stable use of retinoids that are structurally extremely unstable.

[0003]

As described above, retinoids are extremely unstable structurally, easily react with light, air, heat, metal ions and the like, and are deteriorated to lose their effectiveness.
It was difficult to formulate it into a skin external preparation. The present invention
It is intended to improve the stability of retinoids so that it can be used in combination with an external preparation for skin.

[0004]

Means for Solving the Problems The present inventor has made intensive studies in view of the above circumstances, and as a result, as a means for remarkably improving the stability of retinoids, coexistence of vitamin E and amino sugar as essential components. Was found to be extremely effective, and the present invention was completed.

[0005]

DETAILED DESCRIPTION OF THE INVENTION Retinoids, which are essential components of the present invention, are compounds exhibiting vitamin A activity, and are a general term for compounds which in vivo function as a complex of retinoic acid finally bound to a binding protein. Therefore, various isomers of retinoic acid and / or salts, esters, amides thereof, various isomers of retinol and / or esters thereof, various isomers of retinal and / or acetals thereof, Schiff bases And the like, and the isomer is preferably an all-trans type or a 13-cis type.
More specifically, retinoic acid derivatives include metal salts, organic amine salts, esters with monohydric alcohols, esters with polyhydric alcohols, esters with phenols, phosphate esters, phospholipid complexes, Retinoic acid amide and the like;
Fatty acid esters such as palmitic acid esters, phosphate esters, phospholipid complexes, ethers with monohydric alcohols, ethers with polyhydric alcohols, etc. In the case of retinal derivatives, Schiff bases with primary amines, acetal with primary alcohols, Acetals with polyhydric alcohols are exemplified. The retinoids may be not only one kind but also a mixture, and may be a fatty oil or an extract obtained from a tissue of a marine animal containing the retinoids.

[0006] Vitamin E, which is another essential component of the present invention, is 2-methyl-6, which is essential as a radical scavenger.
-A general term for various compounds having a chromanol structure, including α-tocopherol, β-tocopherol, γ-tocopherol, δ-tocopherol, ε-tocopherol, and trans and cis isomers of tocotrienol corresponding to each tocopherol. Also, d, l,
There is a dl isomer. Derivatives include fatty acid esters such as acetates, carboxylic esters, phosphates and salts thereof, and phospholipid complexes.

[0007] Another essential ingredient of the present invention is an amino sugar, Is a generic term for monosaccharides, polysaccharides, glycolipids, etc., and their derivatives, which have the structure of Natural polymers include compounds derived therefrom, and examples of natural polymers include a wide range of distributions such as chitin, glycosaminoglycan, mucopolysaccharide, and cell wall polysaccharide. A readily available example is a mixture of chitosan produced by hydrolysis of chitin, which is economically advantageous, and compounds derived from this product are also highly economical. In addition, the basicity of the amino group of the amino sugar is weak, and the amino group also has a function of keeping the pH constant from a weakly acidic region of about pH 5.0 to 7.5 required for cosmetics to a weakly alkaline region.

[0008] The type and amount of the retinoids to be incorporated into the external preparation for skin according to the present invention are not particularly limited, and the type and amount can be freely selected according to the intended use of the external preparation for skin.
Usually about 0.0001 to 2% by weight of retinoic acid,
For other compounds, the content is about 0.0005 to 10% by weight.

The type and amount of the vitamin E compounded in the external preparation for skin according to the present invention are not particularly limited, and are selected according to the amount of the retinoid and the degree required for stabilization. When it is blended for the purpose of use as an active ingredient of the external preparation for skin, it is selected depending on the purpose, but it is usually about 0.001 to 10% by weight.

[0010] The amount of amino sugars to be incorporated into the external preparation for skin in accordance with the present invention is not particularly limited, and is selected according to the amounts of retinoids and vitamins E and the degree required for stabilization. P by combination with components
When H buffering action is expected, it is selected accordingly.
Usually, it is about 0.001 to 20% by weight.

[0011] Retinoids are known for their chemical instability due to molecular structures with a high degree of conjugated double bonds,
The heat stability of retinol palmitate was determined by the National Institutes of Health,
Research report by Yoshioka et al. (Pharmaceutical R
essearch, P388-391, Vol. 7, N
O. According to U.S. Pat.
It is disclosed that the residual rate in a syrup is about 76% at 0 ° C. for 30 days.

[0012] Further, there are a number of disclosed examples as shown below as conventional technical examples relating to stabilization of a retinoid composition. That is, in US 3906108, butylhydroxytoluene (BHT) or α-
Tocopherol (α-Toc) is present, US Pat.
No. 547 discloses a gel composition in which one or more of BHT, butylhydroxyanisole (BHA) ascorbic acid (AA), propyl gallate (PG), α-Toc and the like are present.

In US application Ser. No. 07 / 719,264,
(A) a chelating agent and at least one oil-soluble antioxidant; (B) a chelating agent and at least one water-soluble antioxidant; and an antioxidant present in each of the oil and the aqueous phase of the emulsion. The retinoid residual rate is about 60% at 40 ° C. for 13 weeks. Although US Pat. No. 4,826,828 and Bio Advance, BHT and BHA are disclosed, it is shown that the stability of retinoids is such that the effectiveness starts to lose after one month at room temperature.

US Pat. No. 4,720,353 discloses a tanning composition containing a retinoid, vitamin E and citric acid in a water-in-oil emulsion. It should be noted that preservatives and antioxidants (for example, BHA, vitamin C, tocopherol linoleate, etc.) are shown as components that can be optionally added thereto.

[0015] EP 323444-A2 discloses the blending of retinoids with BHA or α-Toc in a water-in-oil emulsion.

JP-A-56-140563 discloses an emulsified skin external preparation containing vitamin A, an antioxidant such as BHT, BHA, and Toc and an ethylenesiaminetetraacetic acid salt (EDTA salt).

JP-A-2-142713 discloses an external preparation using retinoic acid in combination with an ultraviolet absorber.

Japanese Patent Application Laid-Open No. 6-32713 discloses that (A) BH is used together with vitamin A and / or a fatty acid ester thereof.
One or more of oil-soluble antioxidants such as T, BHA, α, β, γ, δ-Toc, nordihydroguaiaretinic acid (NDGA), PG, ascorbyl fatty acid (AFA), and sorbic acid;
An external preparation for skin containing (B) one or more EDTA salts and (C) one or more benzophenone compounds is disclosed.

JP-A-6-32714 discloses that (A) BH is used together with vitamin A and / or a fatty acid ester thereof.
One or more of oil-soluble antioxidants such as T, BHA, α, β, γ, δ-Toc, NDG, (B) one or more of AA, AA salt, isoascorbic acid (IAA), and sorbate;
(C) A skin external preparation containing one or more benzophenone compounds is disclosed.

In JP-A-6-32715, one or more cyclodextrins containing one or more antioxidants and / or ultraviolet absorbers are compounded together with vitamin A and / or fatty acid esters thereof. 6
(Same as -32713) is disclosed.

JP-A-6-32716 discloses one or more butanediols and an oil-soluble antioxidant (JP-A-6-327) together with vitamin A and / or a fatty acid ester thereof.
No. 13) is disclosed.

Japanese Unexamined Patent Publication No. Hei 6-32717 discloses an external preparation for skin containing one or more water-soluble benzophenone derivatives together with vitamin A and / or a fatty acid ester thereof.

JP-A-6-32718 discloses an external preparation for skin containing a basic amino acid (arginine, lysine, hydroxylysine, ornithine, etc.) and one or more salts thereof together with vitamin A and / or a fatty acid ester thereof. I have.

Japanese Patent Application Laid-Open No. Hei 6-32719 discloses an external preparation for skin containing an acidic amino acid (aspartic acid, glutamic acid, pyrrolidonecarboxylic acid) and a salt thereof together with vitamin A and / or a fatty acid ester thereof.

JP-A-6-32720 discloses an external preparation for skin containing vitamin A and / or a fatty acid ester thereof and one or more polar oils selected from pentaerythritol fatty acid esters and / or trimethylolpropane fatty acid esters. I have.

Japanese Patent Application Laid-Open No. 6-32721 discloses an external preparation for skin containing one or more water-swellable clay minerals together with vitamin A and / or a fatty acid ester thereof.

JP-A-6-32774 discloses that a basic amino acid (salt), an acidic amino acid (salt), an oil-soluble benzophenone derivative, a water-soluble benzophenone derivative, a pentaerythritol fatty acid ester, and trimethylol are used together with vitamin A and / or a fatty acid ester thereof. One or more compounds selected from the group consisting of propane fatty acid esters, water-swellable clay minerals, cyclodextrin derivatives containing an antioxidant, cyclodextrin derivatives containing an ultraviolet absorber, and citrate are disclosed. .

JP-A-7-291847 discloses retinols such as retinol, retinal, retinyl acetate, retinyl palmitate and at least one imidazole in a free base form (ketoconazole, miconazole, econazole, itraconazole, fluconazole, terconazole, clotrimazole, Butaconazole, sulconazole) and (A) a chelating agent (E
DTA and its derivatives and salts, one or more of citric acid, tartaric acid and dihydroxyethylglycine) and at least one or more oil-soluble antioxidants (BHT, ascorbic acid palmitate (AP), BHA, α-Toc,
Phenyl α-naphthylamine, hydroquinone, PG, N
DGA), (B) a chelating agent and at least one water-soluble antioxidant (BHT, AA, sodium sulfite,
Sodium metasulfite, sodium bisulfite, sodium thiosulfite, sodium formaldehyde sulfoxylate, IAA, thiosorbitol, thiourea, thioglycolic acid, cysteine hydrochloride, 1,4-diazobicyclo- (2,2,2) -octane And (C) a water-in-oil emulsion skin care composition containing a stabilizing system selected from the group consisting of antioxidants present in each of the oil and water phases of the emulsion.

JP-A-8-193019 discloses a skin care composition comprising an oil-in-water emulsion and one or more retinoids of retinol, retinal, retinyl acetate and retinyl palmitate, having a pH of about 4 to 10 and a low saturation. (A) at least one oil-soluble antioxidant (same as in JP-A-7-291847), (B) a chelating agent (same as in JP-A-7-291847), and (C) a chelate Agent and at least one water-soluble antioxidant (same as in JP-A-7-291847);
(D) a stabilizing system selected from the group consisting of an antioxidant and a chelating agent present in each of the oil and aqueous phases of the emulsion, wherein at least 70% of the retinoid is stored at 40 ° C. for 13 weeks. Are disclosed.

The prior art relating to external preparations for skin is as described above. Other techniques for stabilizing retinoids in aqueous eye drops are disclosed in JP-A-6-247853 and JP-A-6-263.
630, JP-A-6-293638, JP-A-6-2936
39, JP-A-6-340525, JP-A-7-8214
3, JP-A-7-25755, JP-A-7-33650, JP-A-7-118147, and JP-A-9-169624,
Combinations of certain nonionic surfactants and third components are disclosed.

[0031]

Novelty and Inventive Step of the Invention Hitherto, a stabilizing technique for combining the amino sugars of the present invention with retinoids and vitamin Es has not been disclosed. In addition, it is clear from the conventionally disclosed techniques of stabilizing retinoids that the combination of the present invention is not one which can be easily conceived by those skilled in the art.

Further, it is not at all foreseeable that retinoids and vitamin Es can be stabilized when an amino sugar is added to the composition containing retinoids and vitamin Es in the present invention.

However, while the present inventors have been studying stabilization of retinoids, surprisingly, by combining the amino sugars of the present invention with vitamin Es, the chemical stability of the retinoids can be improved. The present invention has been found that the present invention has been remarkably improved and that the effective retinoid content in the external preparation for skin can be extremely effectively prevented from decreasing with time, and the present invention has been completed.

The external preparation for skin of the present invention has an effect that the content of retinoids as an active ingredient can be extremely effectively prevented from decreasing with time, so that the effectiveness as an external preparation for skin is maintained for an extremely long time. , Extremely industrial and inventive.

[0035]

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS The embodiments of the present invention cover a wide range, and any form of external preparation for skin can be used. That is, it is liquid, gel, paste, cream, powder, solid, etc. The degree of the effect of the invention depends on the added amount of essential components, dissolved state, presence of oil phase, aqueous phase, etc. Change.

From other demands for cosmetics, water, hydroxy acids, polyhydric alcohols,
In some cases, a compound having a moisturizing property such as ethanol or a highly polar or functional compound is desired to be added, and this may be disadvantageous to the chemical stability of retinoids.

Since retinoids and vitamin Es are mostly lipophilic compounds and amino sugars are hydrophilic compounds,
It is preferable to coexist a substance that improves the solubility and the degree of dispersion according to the dosage form of the external preparation. For example, a surfactant or a dispersant may be used, and a known surfactant or dispersant may be used. In addition, it is also possible to use an amphiphilic compound in which a hydrophobic group is bonded to an amino sugar. Further, the amino saccharide can be used in a free base state or in a salt state with an acid, and there is no limitation on the acid-base properties of the surfactant in the present invention.

It is to be noted that there are naturally conditions under which the physical stability of the dosage form required as an external preparation for skin and the chemical stability of the present invention can be exhibited, and the amino sugar is used as a free base. The solubility and dispersibility of the compound in the system differ between the case and the case where the compound is used in the form of a salt. In particular, the difference in properties between amino sugars of a polymer compound having a large degree of polymerization is large. In addition, the solubility and dispersibility of an amphiphilic compound in which a hydrophobic group is bonded to an amino sugar vary depending on the balance between hydrophilicity and lipophilicity (HLB).

In terms of polarity, retinoids such as retinoic acid salts, retinol phosphates, sugar esters of retinoic acid, retinoic acid, retinoic acid amide, retinal Schiff base, retinol, retinal, and further retinoic acid esters, Among the exemplified compounds such as tocopheryl retinoic acid, retinal acetal, and retinol esters, there is a large change in polarity,
Similarly, there is a large change in polarity between exemplified compounds such as vitamin Es, for example, vitamin E phosphates, nicotinate, free vitamin E, fatty acid esters, and the like.

These compounds and amino sugars and derivatives thereof are effectively brought into contact with each other in a state without any physical change, and in order to efficiently eliminate generated radicals, a solubilizing system, a dispersion system, and an emulsifying system are used. Although a system can be designed, a system that can easily cope with a change in combination is generally an emulsification system.

The emulsification system is roughly divided into oil-in-water (O /
W) and water-in-oil (W / O), and as a more complex combination, such as water-in-oil-in-water (W / O / W) and oil-in-water-in-oil (O / W / O) types There is. However, embodiments of the present invention are not limited to any of these, and any emulsification system is possible.

The emulsification system can be selected depending on the difference in HLB value, which is an index of the balance between hydrophilicity and lipophilicity of the surfactant, and the production procedure. And an emulsifying system using a fluorinated oil and a fluorinated surfactant can be selected.

In the solubilizing system, other coexisting compounds tend to exert an influence on the physical stability and the chemical stability of the system, but in the emulsifying system, the coexisting compound tends to be less affected. Was seen.

As a general item required for an external preparation for skin, the hydrogen ion concentration (P
H), and its value is preferably about 5.0 to 8.0.
The amino saccharide has a weakly basic acid dissociation constant (PKa) of about 6.4 to 7.0, and about half or more of its abundance is neutralized with an acid. 0 to
It has the function of keeping the PH constant within a practical range between 7.5.

More preferably, the coexistence ratio of an amino sugar and an acid is maintained so as to exert a pH interference function so that the PH falls within a desirable range of about 5.5 to 7.0 as an external preparation for skin.

Although there is no particular limitation on the acid, the stabilization of the emulsified system has an appropriate dissociable salt concentration and the stability of the interface due to the interaction with an ionic surfactant exhibiting surface activity at the interface. Acids that can produce compounds that enhance interfacial stability without loss are preferred.

When a compound in which a protonated amino sugar is present is used as a counter ion of an anionic surfactant having an acid dissociating property, it is controlled by a combination of an acid having no surface activity and an acid having a surface activity. It is possible to

Although the type of the surfactant is not limited by the present invention, the stability of the interface of the emulsified composition, the heating and dissolving conditions required at the time of emulsification, and the affinity between the oil phase and vitamins A and vitamin Es. In consideration of such conditions, it can be selected according to the requirements required for the external preparation for skin, and they can be used in combination.

As the compounding components for improving the physical stability of the emulsifying system and the solubilizing system, carboxyl groups, sulfone groups,
A polymer compound having an acid dissociable group such as a phosphate group and a hydrophobic group can be exemplified. The present invention is not limited to natural, semi-synthetic, and synthetic compounds and the HLB value of the present invention, and can be selected and combined according to the components and the dosage form. If the degree of polymerization of both the amino saccharide and the anionic polymer is extremely large, the resulting ion complex may gel or precipitate, so care must be taken in the design of this system.

It is possible to add other known antioxidants, but when added to the essential component system, a remarkable stabilizing effect is not recognized, and the additive effect is not so high. Most of them. However, when combined with catechins and / or tannins, which are compounds having a special structure, further stabilization of retinols by a synergistic effect was achieved, unlike antioxidants of other structures. Catechins and tannins are complex mixtures extracted from plants, and the present invention is not limited by condensed type, non-condensed type, origin, and the like.

Addition of cysteine or glutathione was effective in stabilizing retinols, but when heated, the odor of volatile sulfur compounds generated by the decomposition of the added cysteine or glutathione was felt, and the skin was used externally. There are some difficulties in practical use as agents.

Other known antioxidants, chelating agents, organic compounds and inorganic compounds that absorb ultraviolet rays, light scattering agents, antibacterial agents, preservatives, etc., which are generally incorporated in skin external preparations. Expected vitamins, tyrosinase inhibitors,
It goes without saying that known compounds such as plant extract components, fragrances, pigments, pigments, oils, humectants, hormones, and anti-inflammatory agents can be used in combination.

The stabilizing effect of the external preparation for skin of the present invention is as follows.
Demonstrated without restriction by the type of container in which the composition is filled, but to maintain a longer absolute time to maintain efficacy,
It is preferable to use a material with a high barrier property to minimize the instability factor of the external world, and it is preferable to use a material that is light-blocking or light-absorbing against the influence of light. If it is not sufficient, a known light absorbing compound may be blended.

Hereinafter, embodiments of the present invention will be described in more detail with reference to examples, but the present invention is not limited thereto.

[0055]

EXAMPLES In the following examples, retinoids were analyzed by liquid chromatography. Column: Inertsil ODS-II. Mobile phase: acetonitrile / chloroform / water. Detector UV300
３５０350 nm. Column temperature 36 ° C to 40 ° C. The composition, the flow rate, and the column temperature of the mobile phase were changed in accordance with the combination of the compositions, and the analysis was performed so that the peaks of the eluted substances did not overlap.

An oil phase and a water phase each having a weight percentage of Table 1 are prepared, and the oil phase is poured little by little into the room temperature air while the water phase is being stirred with a disper blade, followed by emulsification. After adjusting the pH to 6.9 with lactic acid, the mixture is filled in an aluminum tube coated with an epoxy resin on the inner surface and stored in a thermostat.
The stability over time was expressed as a percentage of the residual concentration after the lapse of days with respect to the initial concentration of retinyl palmitate in the composition.

Table 1

In Table 1, the stability of retinyl palmitate is improved in the examples as compared with the comparative examples, which is an effect according to the present invention.

By adjusting the oil phase and the aqueous phase in weight% in Table 2,
The aqueous phase is injected little by little into the place where the oil phase is stirred with air at room temperature in the air at room temperature, and the mixture is emulsified. The resulting mixture is filled in an aluminum tube coated with an epoxy resin on the inner surface and stored in a thermostat. The stability over time was expressed as a percentage of the initial concentration of retinyl acetate in the composition after the number of days elapsed.

Table 2

In Table 2, the stability of retinyl acetate is improved in the examples as compared with the comparative examples, which is an effect according to the present invention.

By adjusting the organic phase and the aqueous phase by weight in Table 3 by weight,
While stirring the aqueous phase in the air at 50 ° C. with a screw blade,
Inject the organic phase little by little, dissolve and cool,
Fill an aluminum tube coated with epoxy resin on the inner surface and store in a thermostat. The stability over time was shown as a percentage of the residual concentration after the lapse of days relative to the initial concentration of retinoic acid in the composition.

In Table 3, the stability of retinoic acid is improved in Examples in comparison with Comparative Examples, which is an effect according to the present invention.

The oil phase and the water phase were adjusted by weight in Table 4 and, while stirring the oil phase in air at room temperature with a screw impeller, the water phase was injected little by little to dissolve it. Into a coated aluminum tube and store in a thermostat. The stability over time was expressed as a percentage of the residual concentration after the lapse of days relative to the initial concentration of retinol in the composition.

Table-4

In Table 4, the stability of retinol is improved in the examples as compared with the comparative examples, which is an effect according to the present invention.

The oil phase and the water phase were adjusted by weight in Table 5 and the oil phase was injected little by little while emulsifying the aqueous phase in the air at room temperature with a disper blade, and then emulsified. Fill the coated aluminum tube and store in a thermostat. The stability over time was expressed as a percentage of the residual concentration after the lapse of days relative to the initial concentration of retinyl palmitate in the composition.

Table 5

In Table 5, the stability of retinyl palmitate is improved in the examples as compared with the comparative examples, which is an effect according to the present invention. Comparative Example 10 of Comparative Example 9
The stabilizing effect of the fifth embodiment with respect to the sixth embodiment is greater than the stabilizing effect of the fifth embodiment, which is the effect according to claim 5.

As is evident from the examples of the present invention, the effect is exhibited in any dosage form, but the stabilizing effect may differ depending on the added component. Although this does not limit the range of the dosage form of the present invention, the emulsion system has a greater degree of freedom than the homogeneous system in terms of the application range and selection range in which the additional components required for cosmetics can be contained. For example, when an alcohol component such as ethanol is to be compounded in combination with an ester component such as retinyl palmitate, the chemical stability of retinyl palmitate is better in an emulsion-based formulation than in a homogeneous formulation such as a cosmetic oil. High in nature. This is presumed to be due to a high transesterification reaction rate in the homogeneous system.

When the counter ion of the amino sugar in the emulsion type dosage form was examined, an anionic surfactant,
In particular, an anionic polymer surfactant having an acid-dissociable group and a hydrophobic group tended to show a favorable effect on the chemical stability of retinoids, including the physical stability of the emulsion.

[0072]

EFFECTS OF THE INVENTION In the external preparation for skin of the present invention, when one or more selected from retinoids, one or more selected from vitamin Es, and one or more selected from amino sugars are blended as essential components, the chemical The stability is remarkably improved, and as a result, it is possible to prevent the effect of the retinoids from decreasing over time, and to maintain the effectiveness of the retinoid-based external preparation for skin for a long period of time. Further, the chemical stability of vitamin Es is also improved, and the effects of vitamin Es in the external preparation for skin can be maintained for a long period of time.

──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. ⁷ Identification symbol FI Theme coat ゛ (Reference) A61K 7/00 A61K 7/00 D 9/107 9/107 SF Term (Reference) 4C076 AA12 AA13 AA17 BB31 CC18 CC23 DD08F DD37A DD37R DD38A DD43Z DD46E DD51Z EE09F EE10F EE27A EE30F EE30Q EE37F EE58Q EE58S FF12 FF14 FF15 FF16 FF17 FF36 FF37 ADFF FF39 FF43 AD172 AC172 AC432 AC 432 AD322 AD332 AD621 AD622 AD661 AD662 BB36 CC02 CC04 CC05 CC06 DD27 DD30 DD31 DD32 DD33 EE01 EE17 FF05

Claims (7)

[Claims] 1. An external preparation for skin, comprising as essential components at least one selected from retinoids, at least one selected from vitamin Es, and at least one selected from amino sugars. 2. The retinoids are various isomers of retinoic acid and / or salts, esters, amides, various isomers of retinol and / or esters thereof,
2. The external preparation for skin according to claim 1, wherein the external preparation is selected from one or more of various isomers of retinal and / or an acetal thereof, a Schiff base and the like. 3. The method according to claim 1, wherein the vitamin E is α-tocopherol, β
Selected from at least one of various isomers such as tocopherol, γ-tocopherol, δ-tocopherol, ε-tocopherol and / or esters thereof, and various isomers of tocotrienol corresponding to each tocopherol and / or esters thereof. The external preparation for skin according to claim 1, wherein the external preparation is used. 4. The skin according to claim 1, wherein the amino sugar is selected from one or more of glucosamine, galactosamine, mannosamine and / or polysaccharides and glycolipids containing these as constituents. External preparation. 5. The external preparation for skin according to claim 1, wherein catechins and / or tannins are blended in addition to retinoids, vitamin Es and amino sugars. 6. The external preparation for skin according to claim 1, wherein the dosage form is an emulsion. 7. The external preparation for skin according to claim 1, wherein a high molecular compound having an acid dissociable group and a hydrophobic group is blended in addition to retinoids, vitamin Es and amino sugars.