JPH0899834A - Skin external agent - Google Patents

Abstract

PURPOSE: To obtain a skin external agent remarkably improved in the stability of α-tocopheryl retinoate by adding the α-tocopheryl retinoate to a water-in-oil type emulsion system. CONSTITUTION: This skin external agent improved in the stability of the α- tocopheryl retinoate as an ingredient effective for preventing and treating skin hyperkeratosis, etc., and preventing and recovering skin aging is prepared by adding the α-tocopheryl retinoate to a water-in-oil type emulsion system comprising an oil component such as liquid paraffin or squalane, an aqueous phase component and a surfactant. The α-tocopheryl retinoate is preferably added in an amount of 0.001-10wt.%, especially 0.01-2.0wt.%, and the oil phase component is also preferably added in an amount of 10.0-50wt.%. The surfactant includes diglycerol dioleate and diglycerol diisostearate. Main additives to be added to the aqueous phase component are glycerol, butylene glycol, etc. The skin external agent is stable against heat, etc., and is little in the deterioration of the activity even when stored for a long period of time.

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 intensive studies in view of such circumstances, the present inventors have found that the stability of α-tocopheryl retinoate can be improved by adding α-tocopheryl retinoate to a water-in-oil emulsion system. The inventors have found that they are significantly improved and have completed the present invention.

That is, the present invention is an external preparation for skin containing α-tocopheryl retinoate, wherein the emulsion type of the system is water-in-oil type (W / O).

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%.

The external preparation for skin of the present invention contains an oil phase component consisting of oil, an aqueous phase component, and a surfactant.
Among them, as the oil component, those usually used for external preparations for skin can be applied. For example, liquid paraffin, squalane, synthetic isoparaffin, petrolatum, solid paraffin,
Hydrocarbon oils such as microcrystalline wax, macadamia nut oil, olive oil, evening primrose oil, sesame oil, castor oil, coconut oil, beef tallow, oils and fats such as palm oil, isopropyl myristate, 2-ethylhexanoic acid triglyceride, cetyl isooctanoate, trimethylol Hydrocarbon ester oils such as propane diisostearate, solid beeswax, carnauba wax, higher saturated fatty acids, semi-solid partially hardened oils, and lanolin can also be used. The compounding ratio of the oil phase component in the external preparation for skin of the present invention is 5.0.
˜95.0% by weight, preferably 10.0-50.
0% by weight. As the surfactant, those having a relatively low HLB which is usually used in W / O emulsion preparations can be applied. For example, diglycerin dioleate, diglycerin diisostearate, PEG400 diisostearate, glycerin monooleate, POE (7) hydrogenated castor oil, distearyldimethylammonium chloride, glycerin monoisostearate, sorbitan sesquioleate. , Sorbitan sesquiisostearate, etc. can be applied. Moisturizing components such as glycerin, butylene glycol, dipropylene glycol, polyethylene glycol, sorbit, mannitol, polyglycerin, etc. can be blended as main additives contained in the aqueous phase component.

As the external preparation for skin of the present invention, in addition to the above-mentioned essential components, any water-in-oil type emulsification base which can be usually applied to external preparations for skin can be used. In particular, gel, paste, and cream are preferable, and moisturizers, oils, surfactants, thickeners, sequestering agents, other ultraviolet absorbers, drugs, and pigments are further used as components for modifying the external preparation for skin. ,
It goes without saying that fragrances can be used together.

[0009]

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

Example 1, Comparative Examples 1 to 3 External skin preparations were prepared according to the formulations shown in Table 1 below. For each of the obtained samples, immediately after preparation and at 40 ° C,
The quantitative value of α-tocopheryl retinoate after 60 days was measured by reverse phase high performance liquid chromatography using a UV detector. The results are also shown in Table 1.

[0011]

[Table 1]
(Wt%) ─────────────────────────────────── Example 1 Comparative Example 1 Comparative Example 2 Comparative Example 3 ─────────────────────────────────── Squalane 25.0 25.0 Residual balance isopropyl palmitate 5.0 5.0 5.0 5.0 Vaseline 5.0 5.0 5.0 5.0 Solid paraffin 3.0 5.0 3.0 3.0 POE (7) hydrogenated castor oil 5.0 --- Oleic acid monoglyceride 3.0 --- cetanol-4.0-POE (60) hydrogenated castor oil-2.0 --- potassium stearate-2.0- -Α-tocopheryl retinoate 0.1 0.1 0.1 0.1 Carotenoid --- 0.01 Butylparaben 0.2 0.2 0.2 0.2 Propylparaben 0.1 0.1 --- BHT 0.05 0.05 0.05 0.05 Glycerin 7.0 7.0 --- Propylene glycol 5.0 5.0 --- PEG4000 2.0 2.0 --- Purification Remainder Remainder − − ─────────────────────────────────── System type W / O Emulsion type O / W Emulsified liquid Liquid ─────────────────────────────────── Quantitative value Immediately after preparation 100% 100% 100% 100 % 40 ° C, 60 days later 95% 75% 62% 71% ────────────────────────────────────

In Example 1, the stability of α-tocopheryl retinoate is improved as compared with Comparative Examples 1 and 2, which is the effect of changing the emulsification system according to the present invention to W / O. Further, Comparative Example 3 is a skin external preparation containing a carotenoid which is known to have a stabilizing effect. Even when compared with this, the skin external preparation of the present invention has an excellent stabilizing effect. I understand.

Example 2 W / O type cream Glyceryl monooleate 1.2% by weight diglyceryl diisostearate 2.2 Organically modified clay mineral (Benton 38) 1.8 Solid paraffin 3.0 Vaseline 8.0 Isopropyl myristate 5.0 Squalane 15.0 α-tocopheryl retinoate 0.25 Butylparaben 0.2 BHT 0.05 Perfume Suitable amount PEG6000 3.0 EDTA · 2Na 0.02 Glycerin 9.0 Purified water The balance

Example 3 W / O type eye cream Solid paraffin 2.0 wt% Microcrystalline wax 6.0 Liquid paraffin 20.0 Isopropyl palmitate 6.0 POE (10) glyceryl triisostearate 2.5 POE (5) hydrogenated castor oil 2.2 diglycerin trioleate 1.2 propylparaben 0.2 BHT 0.05 glycerin 8.0 sorbit solution (70%) 5.0 PEG6000 2.5 purified water balance

Example 4 W / O type hand cream Glyceryl monooleate 1.5% by weight diglyceryl diisostearate 2.1 Organically modified clay mineral (Benton 38) 2.2 Solid paraffin 3.0 Vaseline 5.0 Isopropyl myristate 2.0 Liquid paraffin 15.0 α-Tocopheryl retinoate 0.25 Vitamin E acetate 0.2 Butylparaben 0.2 BHT 0.05 Perfume qs PEG6000 1.0 EDTA · 2Na 0. 02 Glycerin 9.0 Propylene glycol 4.0 Purified water balance

The external preparations for skin of Examples 2 to 4 are all α-
The stability of tocopheryl retinoate was excellent.

[0017]

As described above, since the external preparation for skin containing the α-tocopheryl retinoate of the present invention is stabilized against heat and the like, there is little decrease in activity even after long-term storage, A stable α-tocopheryl retinoate-containing preparation can be prepared.

Continuation of the front page (51) Int.Cl. ⁶ Identification number Reference number within the agency FI Technical indication location A61K 31/355 (72) Inventor Katsunobu Yonezawa 5-3 Tsurugaoka, Oi-cho, Iruma-gun, Saitama Japan Seisei Co., Ltd. Pharmaceutical Research Center

Claims (1)

[Claims] 1. An external preparation for skin containing α-tocopheryl retinoate, wherein the emulsion type of the system is water-in-oil type (W / O).