JPH0899821A - Skin external agent - Google Patents

Abstract

PURPOSE: To obtain a skin external agent having remarkably improved stability of α-tocopheryl retinoate by compounding an oil-soluble antioxidation agent and an oil having a specific iodine value as stabilizers together with α- tocopheryl retinoate. CONSTITUTION: This skin external agent containing stabilized α-tocopheryl retinoate is produced by adding 0.001-10.0wt.% of an oil-soluble antioxidation agent (especially preferably butylhydroxytoluene, butylhydroxyanisole, etc.) and >=0.01wt.% of an oil having an iodine value of >=70 to 0.0001-10.0wt.% of α-tocopheryl retinoate. Preferable examples of the oil-soluble antioxidation agent are α, β, γ, δ-tocopherol, nordihydroguaiaretin, propyl gallate, vitamin C fatty acid ester and sorbic acid in addition to the examples cited above. The oil having an iodine value of >=70 is e.g. linseed oil, tung oil, soybean oil, sesame oil, repeseed oil, avocado oil, olive oil, sardine oil, mackerel oil and oyster oil.

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 remarkably improved.

[0002]

PRIOR ART AND PROBLEMS TO BE SOLVED BY THE INVENTION α-
Tocopheryl retinoate is known to be an effective component for the prevention and treatment of cutaneous keratosis and the like, and for the prevention and restoration of skin aging, and is a useful compound as a pharmaceutical and cosmetic ingredient (Japanese Patent Publication Sho 59). No. 22684, JP-A-53
-15429, JP-A-54-84034,
JP-A-2-300123, etc.). However 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, various attempts have been conventionally made to improve the storage stability of this compound, for example, coexisting with an antioxidant such as ascorbic acid or tocopherol (JP-A-2-300123), carotenoids. It is known that coexistence enhances stability against light and the like (Japanese Patent Laid-Open No. 5-163143). However, the method of coexisting with an antioxidant does not have sufficient stabilizing effect, and when a carotenoid is blended, the base is colored even at a blending amount of about 0.0001% by weight, and thus the desired amount is obtained. Considering that it is not possible to avoid a considerable amount of coloring when trying to add the necessary amount to obtain a stabilizing effect, and in view of the fact that it is necessary to avoid excessive coloring due to the properties of an external skin preparation, it is not possible to add a large amount of carotenoids. There was a problem. For the above reasons, a satisfactory method for stabilizing α-tocopheryl retinoate has not yet been found, and the development of an advantageous stabilizing means has been desired.

[0003]

Means for Solving the Problems As a result of earnest studies in view of such circumstances, the present inventors have found that if α-tocopheryl retinoate and a specific component are added as a stabilizer, α-tocopheryl retinoate is added.
The inventors have found that the stability of tocopheryl retinoate is significantly improved, and have completed the present invention.

That is, the present invention provides (A) α-tocopheryl retinoate, (B) one or more oil-soluble antioxidants, and (C) one or more oils having an iodine value of 70 or more, Is an external preparation for skin characterized by being blended with.

The structure of the present invention will be described in detail below. Α-tocopheryl retinoate used in the present invention,
It is an ester of α-tocopherol and vitamin A acid, and α-tocopherol represents a natural mixed tocopherol containing DL-α-tocopherol, D-α-tocopherol and L-α-tocopherol, and vitamin A acid is retinoin. The acids, namely all-trans-retinoic acid, 13-cis-retinoic acid, 11-cis-retinoic acid, 9-cis-retinoic acid and mixed isomers containing them are shown. Preferred are all-trans-retinoic acid and 13-cis-retinoic acid. Particularly preferred as the α-tocopheryl retinoate used in the present invention is an ester form of DL-α-tocopherol and all-trans-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 or more, and more preferably 0.1.
It is at least 01% by weight. The upper limit of blending is 10.0% by weight or less, preferably 5.0, because of the property as an external preparation for skin.
It is up to wt%, more preferably up to 2.0 wt%.

As the oil-soluble antioxidant compounded in the external preparation for skin of the present invention, butylhydroxytoluene (hereinafter referred to as B
Abbreviated as HT. ), Butylhydroxyanisole (hereinafter abbreviated as BHA), α, β, γ, δ-tocopherol, nordihydroguaiaretin, propyl gallate,
Vitamin C fatty acid esters and sorbic acid are included. Of these, BHT, BHA and α, β,
γ, δ-tocopherol is preferred.

In the present invention, the blending amount of the oil-soluble antioxidant is preferably 0.001% by weight or more, more preferably 0.01% by weight or more. In order to exert the effects of the invention for a longer period, 0.03% by weight or more 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 up to 10.0% by weight in view of the properties as an external preparation for skin.

Examples of the oil having an iodine value (IV) of 70 or more, which is blended for the purpose of exerting the effects of the present invention, include linseed oil, tung oil, soybean oil, safflower oil, walnut oil, which is a vegetable oil belonging to a drying oil. Eno oil, evening primrose oil, cherry kernel oil, grape seed oil, etc .; sesame oil belonging to non-drying oil,
Rapeseed oil, cottonseed oil, bran oil, wheat germ oil and the like; or avocado oil, olive oil, camellia oil, macadamia nut oil and the like; and fish oils such as sardine oil, mackerel oil, herring oil, cod liver oil and oyster oil.

The iodine value (IV) of these oils is, for example, 168 to 190 for linseed oil, 114 to 138 for soybean oil,
122-150 for safflower oil, 94-10 for rapeseed oil
7, cotton seed oil 90-121, olive oil 75-90,
Camellia oil is 73 to 87, sardine oil is 136 to 195, and herring oil is 99 to 119. Further, free fatty acids and higher alcohols derived from these fats and oils having an iodine value of 70 or more include, for example, oleic acid, palmitooleic acid, linoleic acid, linolenic acid, eleostearic acid, γ-linolenic acid, and arachidone. Acids, eicosapentaenoic acid, oleyl alcohol and the like are also included.

One kind or two or more kinds of these oils are blended, but the amount blended for the purpose of exerting the effect of the present invention is 0.01% by weight or more. Does not hinder the effect of. However, if it is blended in a remarkably excessive amount, the quality as an external preparation for skin may be impaired, so caution is required.

In addition to the above-mentioned oil having an iodine value of 70 or more, oils having an iodine value of less than 70 can be used in the external preparation for skin of the present invention. For such oil, squalane,
Liquid paraffin and the like can be mentioned.

In the present invention, as the skin external preparation base to which α-tocopheryl retinoate, an oil-soluble antioxidant and an oil having an iodine value of 70 or more are blended, any conventional skin external preparation base can be used. Available. That is, liquid, gel, paste, cream, powder, solid, etc., as a component for modifying the skin external preparation, moisturizer, oil, surfactant, thickener, sequestering agent, It goes without saying that other ultraviolet absorbers, drugs, dyes, fragrances, etc. can be used in combination.

[0014]

EXAMPLES Examples of the present invention will now be described in detail, but the present invention is not limited thereto.

Examples 1 to 9 and Comparative Examples 1 to 10 Skin external preparations were prepared according to the formulations shown in Tables 1 and 2 below. For each of the obtained samples, immediately after preparation and 50
Quantitative value of α-tocopheryl retinoate after 10 days at ℃ was measured by reverse phase high performance liquid chromatography using UV.
It measured using the detector. The results are also shown in Tables 1 and 2
Shown in.

[0016]

[Table 1]
(% By weight) ───────────────────────────────── Actual example ────────── ───────────── 1 2 3 4 5 6 7 8 9 ────────────────────────────── ───── Olive oil (IV = 75) 99.0 − − − − − − − − Cotton seed oil (IV = 95) − 99.0 − 99.0 99.0 99.0 99.0 99.0 99.0 Evening primrose oil (IV = 190) − − 50.0 − − − − − − Squalane (IV = 1) − − 49.0 − − − − − − Palm oil (IV = 12) − − − − − − − − − BHT 0.02 0.05 0.05 − − − − − − δ-tocopherol − − − 0.05 − − − − − BHA − − − − 0.05 − − − − Nordicitate logger Ayaretin − − − − − 0.05 − − − Propyl gallate − − − − − − − 0.05 − − Betamine C fatty acid ester − − − − − − − 0.05 Sorbic acid − − − − − − − − 0.05 α-Tocopheryl retinoate 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 ───────────────────────── ───────── α-tocopheryl retinoate Quantitative value Immediately after preparation 100% 100% 100% 100% 100% 100% 100% 100% 100% 50 ° C, 10 days later 93% 98% 97% 96% 98% 92% 92% 91% 93% ─────────────────────────────────

[0017]

[Table 2]
(% By weight) ─────────────────────────────────── Comparison ───────── ───────────────── 1 2 3 4 5 6 7 8 9 10 ─────────────────────── ──────────── Olive oil (IV = 75) − − − − − − − − − − Cottonseed oil (IV = 95) − − − 99.0 − − − − − − Evening primrose oil (IV = 190) ) − − − − − − − − − − Squalane (IV = 1) 49.0 49.0 99.0 − 49.0 49.0 49.0 49.0 49.0 49.0 Palm oil (IV = 12) 50.0 50.0 − − 50.0 50.0 50.0 50.0 50.0 50.0 BHT 0.05 − 0.05 − − − − − − − Δ-Tocopherol − 0.5 − − − − − − − − BHA − − − − − 0.5 − − − − Nordigitrolog Ayaretin − − − − − − 0.5 − − − Propyl gallate − − − − − − − 0.5 − − Min C fatty acid ester − − − − − − − − 0.5 − sorbic acid − − − − − − − − − 0.5 carotenoid − − − − 0.01 − − − − − α-tocopheryl retinoate 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 ─────────────────────────────────── α-tocopheryl retinoate Quantitative value Immediately after preparation 100% 100% 100% 100% 100% 100% 100% 100% 100% 100% 50 ° C, 10 days later 58% 68% 39% 51% 82% 59% 42% 51% 46% 57% ─────── ────────────────────────────

In Examples 1 to 9, the stability of α-tocopheryl retinoate is improved as compared with Comparative Examples 1 to 10, which is an effect according to the present invention. In addition, Comparative Example 5
Is a skin external preparation containing a carotenoid, which is known to have a stabilizing effect, and it can be seen that the skin external preparation of the present invention also has an excellent stabilizing effect in comparison with this.

[0019] The oil phase portion of A and the water phase portion of B are dissolved by heating at 70 ° C., and A is added to B and emulsified. Then, it is cooled to obtain a cream.

[0020] Each of the above raw materials is heated and melted at 80 ° C., and then poured into a predetermined container to obtain a lip stick.

Example 12 Lotion A lotion was prepared according to the following formulation. α-tocopheryl retinoate 0.0001% by weight oleyl alcohol (IV = 80) 0.01 α-tocopherol 0.005 POE (20) octyldodecanol 0.8 ethanol 8.0 propylene glycol 3.0 glycerin 1.0 Methylparaben 0.15 Lactic acid 0.01 Sodium lactate 0.09 Purified water balance

Example 13 Eye Wrinkle Oil An eye wrinkle oil was prepared according to the following formulation. Macadamia nut oil (IV = 75) 40.0% by weight γ-linolenic acid triglyceride (IV = 198) 1.0 2-ethylhexanoic acid triglyceride 25.0 Safflower oil (IV = 130) 20.0 Squalane 10.0 PEG600 Dioleate 2.8 δ-tocopherol 1.0 α-tocopheryl retinoate 0.2

The skin external preparations of Examples 10 to 13 were all excellent in the stability of α-tocopheryl retinoate in daily use.

[0024]

As described above, in the external preparation for skin of the present invention, the stability of α-tocopheryl retinoate is remarkably improved by blending an oil-soluble antioxidant and an oil component having an iodine value of 70 or more. be able to.

─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. ⁶ Identification number Reference number within the agency FI Technical indication location A61K 47/12 K 47/14 K 47/22 K 47/44 J (72) Inventor Katsunobu Yonezawa 5-3-1 Tsurugaoka, Oi-cho, Iruma-gun, Saitama Nisshin Seifun Co., Ltd.

Claims (3)

[Claims] 1. (A) α-tocopheryl retinoate,
(B) one or more oil-soluble antioxidants, and (C) one or more oil components having an iodine value of 70 or more;
An external preparation for skin characterized by being blended with. 2. The (B) oil-soluble antioxidant is butylhydroxytoluene, butylhydroxyanisole, α, β,
γ, δ-tocopherol, nordihydroguaiaretin,
The external preparation for skin according to claim 1, which is selected from the group consisting of propyl gallate, vitamin C fatty acid ester and sorbic acid. 3. The component (A) 0.0001 to 10.0% by weight, the component (B) 0.001 to 10.0% by weight, and the component (C) 0.01% by weight or more are blended. Or the external skin preparation described in 2.