JP3493459B2 - 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 a skin external preparation, and more particularly to a skin external preparation containing urea and a specific amount of γ-oryzanol.

[0002]

[Prior art and its problems] Dry skin disease is a disease represented by senile xerosis and atopic skin, and changes in the housing environment (low humidity) due to the spread and sealing of air conditioning and the elderly It has been increasing rapidly in recent years with the increase in the number of layers. All of the dry skin diseases are accompanied by itchiness and are accompanied by the symptoms of dryness and roughening of the skin, mainly in the trunk, which develop and worsen during the cold and low-humidity winter season. Decreased amounts of sebum and stratum corneum have been revealed. For example, in senile xerosis, sebum secretion, cutaneous blood flow, and insensitive evaporative decrease due to deterioration of skin function due to aging, and physiological changes due to the above-mentioned changes in the housing environment and skin Develop the dry situation.

[0003] By the way, conventionally, for patients with the above-mentioned dry skin diseases, a moisturizing agent for keeping the water content of the stratum corneum, such as urea and vitamins, is provided along with life guidance that does not promote the dryness of the skin. A, vitamin E, heparin analogues, etc., and supplementarily natural moisturizing factors (amino acids, lactates, electrolytes, etc.), polyhydric alcohols (glycerin, polyethylene glycol, etc.), water-soluble polymers (hyaluronic acid, Topical application of collagen, etc. is performed.

However, the currently known external preparations are intended exclusively for retaining the water content of the skin as described above, and are still reluctant to retain oil and improve the amount of sebum (by promoting sebum secretion, etc.). However, research and development of effective drugs have hardly been conducted. For example, γ-oryzanol, cholesteryl isostearate, androgen, bryonolic acid and the like are known as substances having a sebaceous gland activating action, but in addition to γ-oryzanol, there have been cases where attempts were made to apply to this external preparation. However, γ-oryzanol itself is a mixture of several kinds of components, and the quality (grade) is not constant depending on the route obtained, and the effect of its use varies, and therefore, sufficient research / It was in the present condition that it has not been developed.

Therefore, the object of the present invention is not only a moisturizing effect but also an effect on a skin external preparation, in particular because it has an effect of improving a decrease in the amount of sebum, and in particular, it is a dry skin disease such as xerosis. The present invention is to provide a new external preparation for skin that can exert excellent preventive and therapeutic effects against

[0006]

Means for Solving the Problems As a result of earnest research by the present inventors, the ferulic acid ester content of phytosterols, which is one of the constituents of γ-oryzanol, was found to improve the sebum amount of γ-oryzanol. It has been found that its content is 20% or more, and that it succeeds in the production and purification of the product, and when the specified amount is used in combination with the specified amount of urea, a new external topical skin meeting the above-mentioned purpose It has been found that an agent can be provided. The present invention has been completed based on such findings.

That is, according to the present invention, 8 to 23% by weight of urea and 0.5 to 5% by weight of γ-oryzanol having a ferulic acid ester content of phytosterols of 20% or more.
There is provided a skin external preparation characterized by containing as an essential component, particularly the above skin external preparation having a γ-oryzanol content of 1 to 4% by weight.

In the external preparation for skin of the present invention, it is important to utilize the above specified γ-oryzanol as one of the essential components. The γ-oryzanol includes phytosterols (campesterol, stigmasterol, β
-Sitosterol, etc.) with a ferulic acid ester content of 2
As long as the content is 0% or more, the origin (raw material), the production method, the purification method, etc. are not particularly limited, but, for example, according to the study by the present inventors, the production can be performed as follows.

That is, first, according to a refining operation of edible rice oil, a concentrated alkaline solution is added to rice bran crude oil to neutralize and deoxidize most of fatty acids. Next, the primary foots are removed by centrifugation to obtain a primary deoxidized oil, which is made weakly alkaline by adding a dilute alkaline solution, and the neutral oil, fatty acids and the like are completely separated by centrifugation to obtain a secondary foot. The above secondary foots,
Neutralize with sulfuric acid and wash thoroughly with water to obtain a secondary dark oil.
This dark oil usually contains 25-30% γ-oryzanol.

The secondary dark oil was dehydrated under reduced pressure, sulfuric acid and methanol were added to methylate fatty acids, and the mixture was washed with water to remove sulfuric acid, and then mixed solvent (benzene,
Ion exchange resin tower (OH type)
Γ-oryzanol is adsorbed through the. After confirming that γ-oryzanol does not leak from the exchange resin tower, acetic acid was added to the mixed solvent to desorb γ-oryzanol, and methanol and acetic acid were washed and removed from the desorption solution,
Removal of the solvent gives crude γ-oryzanol.
The crude γ-oryzanol obtained in this step is usually 80-
It contains γ-oryzanol at a concentration of 95%, and this does not show any change in its composition with that of the raw dark oil.

To the crude γ-oryzanol, 30 to 50% of urea, benzene and methanol are added and mixed,
A urea adduct is obtained. By repeatedly washing this urea adduct with n-hexane, the purity can be improved to 93 to 97%. Thereafter, water was added to hydrolyze to completely remove urea, followed by drying. The dried product was dissolved in about 20 times the amount of acetone, and activated carbon was added to remove phospholipids while decolorizing, After distilling off acetone and replacing with the mixed solvent,
Heavy metals are removed through an ion exchange resin tower (H + type). Finally, after removing the mixed solvent, it is replaced with n-hexane, cooled, and the crystallized crystals are filtered off and dried to give a desired phytosterols having a ferulic acid ester content of 20% or more. Obtain purified γ-oryzanol.

The γ-oryzanol used in the present invention preferably has a ferulic acid ester content of phytosterols in the range of about 20 to 30%.

The ferulic acid ester content of the above phytosterols is determined by hydrolyzing the sample with an alkali (for example, a KOH + isopropyl alcohol mixed solution), cleaving the ester portion, removing the alkali, and drying ethyl acetate. In addition, the content of the phytosterols (peak area percentage) obtained by gas chromatography analysis under the conditions described in detail in the section of Examples below will be displayed.

The above-mentioned γ-oryzanol is contained in the external preparation of the present invention in an amount of 0.5 to 5% (w / w%, the same applies hereinafter), preferably 1%.
It is blended in the range of ˜4%, and by this blending, the intended effect of the present invention can be achieved.

Urea, which is used as the other essential component in the external preparation for skin of the present invention, has been conventionally used as a medicinal component in this external preparation for skin, especially in the dry skin treatment agent, and its compounding amount is , An effective amount capable of exerting the above-mentioned medicinal effect, 8 to 23% (w / w%, the same applies hereinafter) of the external preparation usually obtained, preferably about 10 to 20%. When used, the intended effect of the present invention can be obtained.

In the external preparation of the present invention, except that the above-mentioned γ-oryzanol and urea are contained as essential components, the base component and other various additives used therein, the preparation method of the external preparation itself, etc. Can also follow the usual methods.

The above base components can be appropriately determined by those skilled in the art, except for 10% or more of purified water necessary for dissolving urea, depending on the intended form of the external preparation (ointment, cream, lotion, etc.). And a wide range of additives that can be used in ordinary external preparations.

As the base oily component, saturated hydrocarbons (white petrolatum, liquid paraffin, etc.), waxes (egg beeswax, carnauba wax, etc.), fats and oils (soybean oil, hard fat, etc.), higher alcohols (ethanol, Stearyl alcohol, oleyl alcohol, cholesterol, etc.), esters (diisopropyl adipate, diisopropyl sebacate, octyldodecyl myristate, cetyl lactate, etc.), fatty acids (palmitic acid, stearic acid, oleic acid, etc.), silicone oil (methyl poly) Siloxane, etc.), vitamin derivatives (retinol palmitate, tocopherol acetate, etc.), etc., or a mixture thereof. Examples of the aqueous component include alcohols (ethanol, isopropyl alcohol, etc.), polyhydric alcohols (1,3 -Butyling Call, glycerine, propylene glycol, polyethylene glycol, etc.), water-soluble polymers (methylcellulose, ethylcellulose, carboxyvinyl polymers, polyvinyl pyrrolidone, water-soluble collagen, hyaluronic acid and the like), amino acids (glycine,
Alanine, etc.), others (citric acid, phosphoric acid, lactic acid, sodium lactate, sodium chloride, etc.), and mixtures thereof.

Further, perfumes such as methylparaben, propylparaben, butylparaben and the like as preservatives, dibutylhydroxytoluene, tocopherol and the like as antioxidants can also be exemplified, and polyoxyethylene alkyl ether, polyoxyethylene alkylphenyl ether as emulsifiers. , Polyoxyethylene polyoxypropylene cetyl ether, tetraoleic acid polyoxyethylene sorbit, trioleic acid polyoxyethylene sorbitan, polyoxyethylene castor oil, polyoxyethylene hydrogenated castor oil, polyoxyethylene sorbit beeswax, sucrose fatty acid ester, Polyglycerin fatty acid ester, polyoxyethylene lanolin, polyoxyethylene lanolin alcohol, polyoxyethylene stearamide, lecithin , Mono-fatty acid polyethylene glycol, mono fatty acid glycerin, mono-fatty acid propylene glycol mono fatty acid sorbitan, sodium lauryl sulfate, sodium cetyl sulfate, polyoxyethylene alkyl ether phosphates, or this like mixture of the exemplified.

Other medicinal ingredients for symptoms other than dry skin that can be incorporated into the external preparation of the present invention include antihistamines (diphenhydramine, chlorpheniramine maleate, etc.), local anesthetics (aminobenzoic acid) for the purpose of antipruritic purposes. Ethyl, lidocaine, etc.), antiphlogistic antipruritic agents (camphor, menthol, etc.), others (crotamiton, glycyrrhetinic acid, etc.), etc., or mixtures thereof can be exemplified.

The external preparation for skin of the present invention thus prepared is
This is filled in a suitable container to obtain a product, which can be applied by dripping, applying or the like in an appropriate amount to the affected part in one day, or can be filled in a spray container and applied by a spraying method.

[0022]

The external preparation for skin of the present invention has both a moisturizing action and an action of improving the decrease in sebum amount, and can be applied to the skin of patients with dry skin disease to exert an excellent therapeutic effect on skin improvement. .

[0023]

EXAMPLES In order to explain the present invention in more detail, preparation of γ-oryzanol having a ferulic acid ester content of the phytosterols used in the present invention of 20% or more (hereinafter referred to as “γ-oryzanol A”) will be described below. Examples are given as reference examples, and then, formulation examples of the external preparation for skin of the present invention (Examples 1 to 1
6) and the respective formulation examples of the comparative skin external preparation and the comparative skin external preparation are given as Comparative Example 1 and Control Example 1, respectively, and further test examples carried out for each of these skin external preparations.

The ferulic acid ester content of the phytosterols of γ-oryzanol A in the reference example was determined by hydrolyzing the sample with an alkali (KOH + isopropyl alcohol mixed solution) to cleave the ester portion, then removing the alkali and drying. A liquid prepared by redissolving the sample thus obtained in ethyl acetate was used as a sample, and the content of phytosterols in the sample was analyzed by gas chromatography (G
C) The value (area percentage;%) obtained by analysis is used. The content rate of γ-oryzanol C in Comparative Example 1 described later is also the same as that of GC
It was obtained by analysis.

<GC measurement conditions> Column: Silicone OV-17, 2.0%, on chromosorb W
(AW-DMCS) 80-100 mesh, 3.2φ × 2.1 m Column temperature: 280 ° C. Injection temperature: 310 ° C. Detection temperature: 310 ° C. Carrier gas: N 2 gas or He gas (0.75 kg /
cm ² )

[0026]

[Reference Example 1] To 1000 g of rice bran crude oil, 65 g of 5N-NaOH solution was added to neutralize and deoxidize most of the fatty acids. Then, the primary foots were removed by centrifugation (5000 rpm, 30 minutes) to obtain 840 g of primary deoxidized oil, and 1N-
A NaOH solution is added to make it weakly alkaline (pH 9), and the oil is removed by centrifugation (5000 rpm, 30 minutes) to obtain 150 g of secondary foots. The secondary foots are neutralized with sulfuric acid and thoroughly washed with water to obtain 40 g of secondary dark oil. This dark oil contains 25-30% γ-oryzanol.

40 g of the secondary dark oil was dehydrated under reduced pressure, 5 g of sulfuric acid and 400 ml of methanol were added to methylate the fatty acid, and the mixture was washed with water to remove sulfuric acid and methanol, and then mixed solvent (benzene: methanol = 3: 1)
It is dissolved in 800 ml and γ-oryzanol is adsorbed through an ion exchange resin tower (OH type, IRA-401 manufactured by Organo). After confirming that γ-oryzanol did not leak from the exchange resin tower, 40 g of acetic acid was added to the mixed solvent.
Is added to desorb γ-oryzanol, methanol and acetic acid are removed from the desorption solution by washing with water, and the solvent is removed to obtain 12 g of crude γ-oryzanol. The crude γ-oryzanol obtained in this step usually has a γ concentration of 80 to 95%.
-Contains oryzanol, which does not show any change in composition with that of raw dark oil.

30 to 5 is added to 12 g of the above crude γ-oryzanol.
7.2 g of 0% urea, 40 ml of benzene and 150 ml of methanol were added and mixed, and the solvent was distilled off to obtain 20 g of a urea adduct. The urea adduct was repeatedly washed with n-hexane three times to obtain 18 g of a crude adduct of γ-oryzanol with a purity of 93 to 97%. After that, water was added to hydrolyze to remove urea and then dried.
Dissolve the dried product in about 20 times the amount of acetone, add activated carbon to decolorize and remove phospholipids, distill off acetone, and replace with the above mixed solvent.
⁺ Type, IR-200C manufactured by Organo Co., Ltd., to remove heavy metals, and finally to remove the mixed solvent, and then to replace with n-hexane, and to cool crystals which crystallize and are separated by filtration and dried. 6 g of desired purified γ-oryzanol (γ-oryzanol A, ferulic acid ester content of phytosterols: 24%) was obtained.

[0029]

Example 1 Preparation of Cream γ-Oryzanol A 1.0 g Urea 10.0 g Propylparaben 0.1 g Methylparaben 0.1 g Diisopropyl adipate 10.0 g White petrolatum 20.0 g Salami beeswax 1.0 g Cetanol 3.0 g Mono Glycerin stearate 4.0 g Sorbitan monostearate 2.0 g Polyethylene glycol monostearate 1.0 g 1,3-butylene glycol 10.0 g Purified water balance 100.0 g γ-oryzanol A was added to diisopropyl adipate. Dissolve with heating, and add propylparaben, white petrolatum, white beeswax, cetanol, glyceryl monostearate, sorbitan monostearate and polyethylene glycol monostearate, dissolve with heating and dissolve the oil phase. Prepared.

Separately, urea was added to purified water and dissolved by heating,
Methylparaben and 1,3-butylene glycol were added to each and dissolved by heating to prepare an aqueous phase.

The above aqueous phase was gradually added to the above oil phase with heating and stirring to emulsify, and the mixture was further cooled to room temperature with vigorous stirring with a homomixer to prepare a cream type external preparation for skin of the present invention. .

[0032]

Example 2 Preparation of lotion agent γ-oryzanol A 1.0 g Urea 10.0 g Methylparaben 0.1 g Diisopropyl sebacate 5.0 g Tetraoleic acid polyoxyethylene sorbite 1.0 g 1% carboxyvinyl polymer aqueous solution 50.0 g propylene Glycol 10.0 g Purified water Residual total 100.0 g To γ-oryzanol A, diisopropyl sebacate and polyoxyethylene sorbite tetraoleate were added and dissolved by heating to prepare an oil phase.

Separately, purified water is added to urea and methylparaben,
Propylene glycol and 1% carboxyvinyl polymer aqueous solution were added and dissolved by heating to prepare an aqueous phase.

The above aqueous phase was gradually added to the above oil phase with heating and stirring to emulsify, and the mixture was further cooled to room temperature with vigorous stirring with a homomixer to prepare a lotion type external preparation for skin of the present invention. .

[0035]

Example 3 Preparation of Cream γ-Oryzanol A 4.0 g Urea 20.0 g Butylparaben 0.1 g Methylparaben 0.1 g Liquid paraffin 30.0 g Salami beeswax 15.0 g Stearyl alcohol 2.0 g Sorbitan monostearate 2. 0 g Polyoxyethylene sorbitan monostearate 3.0 g Purified water Residual total 100.0 g γ-oryzanol A, butyl paraben, liquid paraffin, salix beeswax, stearyl alcohol, sorbitan monostearate and polyoxyethylene sorbitan monostearate are mixed. Then, the mixture was heated and dissolved to prepare an oil phase.

Separately, urea, methylparaben and purified water were mixed and dissolved by heating to prepare an aqueous phase.

The above aqueous phase was gradually added to the above oil phase under heating and stirring to emulsify, and the mixture was further cooled to room temperature with vigorous stirring with a homomixer to prepare a cream-type external preparation for skin of the present invention. .

[0038]

Example 4 Preparation of Cream γ-Oryzanol A 2.0 g Urea 10.0 g Propylparaben 0.1 g Methylparaben 0.1 g Hardfat 1.0 g Octyldodecyl myristate 1.0 g Stearyl alcohol 3.0 g Cholesterol 1.0 g Cetyl lactate 2.0 g Methyl polysiloxane 6.0 g Glycerin monostearate 1.0 g Self-emulsifying glyceryl monostearate 7.0 g Sorbitan stearate 1.0 g Polyethylene glycol monostearate 4.0 g Glycerin 12.0 g 1% carboxyvinyl aqueous polymer solution 20.0g purified water residual part total 100.0 g .gamma.-oryzanol A, propylparaben, hard fat, octyldodecyl myristate, stearyl alcohol, cholesterol, cetyl lactate Methyl polysiloxane, glyceryl monostearate, self-emulsifying glycerin monostearate, sorbitan monostearate and polyethylene glycol monostearate were mixed,
It melt | dissolved by heating and the oil phase was prepared.

Separately, urea, methylparaben, glycerin, 1% carboxyvinyl polymer aqueous solution and purified water were mixed and dissolved by heating to prepare an aqueous phase.

The above aqueous phase was gradually added to the above oil phase under heating and stirring to emulsify, and the mixture was further cooled to room temperature with vigorous stirring with a homomixer to prepare a cream type external preparation for skin of the present invention. .

[0041]

Example 5 Preparation of Cream γ-Oryzanol A 1.0 g Urea 10.0 g Propylparaben 0.1 g Methylparaben 0.1 g Hardfat 1.0 g Octyldodecyl myristate 1.0 g Stearyl alcohol 3.0 g Cholesterol 1.0 g Cetyl lactate 2.0 g Methyl polysiloxane 6.0 g Glycerin monostearate 1.0 g Self-emulsifying glyceryl monostearate 7.0 g Sorbitan stearate 1.0 g Polyethylene glycol monostearate 4.0 g Glycerin 12.0 g 1% carboxyvinyl Polymer aqueous solution 20.0 g Purified water Residual total 100.0 g A cream type external preparation for skin of the present invention was prepared in the same manner as in Example 4 using the above components.

[0042]

Example 6 Preparation of Cream γ-Oryzanol A 4.0 g Urea 10.0 g Propylparaben 0.1 g Methylparaben 0.1 g Hardfat 1.0 g Octyldodecyl myristate 1.0 g Stearyl alcohol 3.0 g Cholesterol 1.0 g Cetyl lactate 2.0 g Methyl polysiloxane 6.0 g Glycerin monostearate 1.0 g Self-emulsifying glyceryl monostearate 7.0 g Sorbitan stearate 1.0 g Polyethylene glycol monostearate 4.0 g Glycerin 12.0 g 1% carboxyvinyl Polymer aqueous solution 20.0 g Purified water Residual total 100.0 g A cream type external preparation for skin of the present invention was prepared in the same manner as in Example 4 using the above components.

[0043]

Example 7 Preparation of Cream γ-Oryzanol A 0.5 g Urea 10.0 g Propylparaben 0.1 g Methylparaben 0.1 g Hardfat 1.0 g Octyldodecyl myristate 1.0 g Stearyl alcohol 3.0 g Cholesterol 1.0 g Cetyl lactate 2.0 g Methyl polysiloxane 6.0 g Glycerin monostearate 1.0 g Self-emulsifying glyceryl monostearate 7.0 g Sorbitan stearate 1.0 g Polyethylene glycol monostearate 4.0 g Glycerin 12.0 g 1% carboxyvinyl aqueous polymer solution 20.0g purified water residual part total 100.0 g .gamma.-oryzanol A, propylparaben, hard fat, octyldodecyl myristate, stearyl alcohol, cholesterol, cetyl lactate Methyl polysiloxane, glyceryl monostearate, self-emulsifying glycerin monostearate, sorbitan monostearate and polyethylene glycol monostearate were mixed,
It melt | dissolved by heating and the oil phase was prepared.

Separately, urea, methylparaben, glycerin, 1% carboxyvinyl polymer aqueous solution and purified water were mixed and dissolved by heating to prepare an aqueous phase.

The above aqueous phase was gradually added to the above oil phase with heating and stirring to emulsify, and the mixture was further cooled to room temperature with vigorous stirring with a homomixer to prepare a cream type external preparation for skin of the present invention. .

[0046]

[Comparative Example 1] The same as in Example 4 except that commercially available γ-oryzanol (ferulic acid ester content of phytosterols = 15%, hereinafter referred to as “γ-oryzanol C”) was used instead of γ-oryzanol A. To obtain a comparative skin external preparation in the form of a cream.

[0047]

Comparative Example 1 A cream-type external preparation for external control was obtained in the same manner as in Example 4 except that γ-oryzanol A was not added.

[0048]

[Test Example 1] γ-oryzanol sebaceous gland activation test 1) Application of test sample Female Syrian golden hamster (10-12 weeks old)
To the inner skin of the auricle of the present invention, the external preparation for skin of the present invention (cream) obtained in Examples 4 to 6 and the external preparation for skin obtained in Comparative Example 1 and Control Example 1 were each once a day for 14 consecutive days. Applied. The application was performed in the morning, and the application amount was 1 drop (about 0.05 ml) from a pipette. Further, in order to eliminate the influence of individual differences among the test animals, at least three animals were used for the same sample, and the left and right ears of each animal were randomly applied with different test samples.

2) Collection of skin pieces The day after the end of the application period in 1) above (1 from the start of the test)
On the 5th day), each hamster was suffocated with CO ₂ gas and slaughtered, and a skin piece on the inner center of the auricle skin was collected with a punch having a diameter of 6 mm.

3) Measurement of the area of the sebaceous gland The area of the sebaceous gland was measured by the Wholemant method (WMT, Whole Mount Technique, Journal of Dermatolo) as follows.
gy, Vol.15: 252-256 (1988)). That is,
The collected auricle skin pieces were immersed in physiological saline at 4 ° C for 18 hours, and then the cartilage was removed, followed by 37 ° C for 2 hours, 2N-NaBr.
Immerse in an aqueous solution, peel the epidermis, create a dermis sheet,
This is stained with Sudan III, 20 per ear
The area of the sebaceous glands in the three places is a three-dimensional image analysis device (Olympus Color Image Analyzer,
CIA-102) used).

4) Results and Statistical Analysis The results obtained in 3) above are shown in FIG. Figure 1 is a sebaceous gland area on the vertical axis (mm ^2/100), takes the horizontal axis γ- oryzanol concentration (%), measured values of each sample (mean ± S.
D) is plotted and made into a graph, and (1) to (5) in the figure show the following samples, respectively.

(1) Sample for external preparation for skin obtained in Control Example 1 (2) Sample for external preparation for skin according to the present invention obtained in Example 5 (3) Sample for external preparation for skin according to the present invention obtained in Example 4 ( 4) ... Sample of external preparation for skin of the present invention obtained in Example 6 (5) ... Sample of external preparation for skin obtained in Comparative Example 1 In the figure, after multiple analysis of each data, multiple comparison by Tukey method is performed. The significant difference test results (determined to be significant) obtained by the above are displayed with the following marks.

*: Sample for external preparation for skin (1) obtained in Control Example 1
P <0.01 # ... p <for the skin external preparation sample (5) obtained in Comparative Example 1
0.05 5) Discussion From the above results, the sample of the present invention containing γ-oryzanol having a ferulic acid ester content of phytosterols of 20% or more as compared with the sample (1) without γ-oryzanol as a control. It was confirmed that the addition of 1% or more of (2) to (4) exerts a significant sebaceous gland increasing action or sebaceous gland activating action.

On the other hand, a normal commercial γ-containing compound having a ferulic acid ester content of phytosterols of less than 20%.
In the comparative sample (5) containing oryzanol, although the sebaceous gland activating action is recognized as compared with the control sample (1),
No significant difference was observed.

From the above, the skin external preparation of the present invention is based on the fact that the above-mentioned specific γ-oryzanol is blended.
It is clear that it can activate the sebaceous gland function and exert a sebum secretion promoting action, and thus is effective for the prevention and treatment of dry skin diseases such as xeroderma and the like in which the amount of sebum is reduced.

[Brief description of drawings]

FIG. 1 is a graph showing the results of measuring the sebaceous gland area by using the skin external preparation sample of the present invention performed according to Test Example 1.

─────────────────────────────────────────────────── ─── Continuation of front page (51) Int.Cl. ⁷ Identification code FI A61K 31/575 A61K 31/575 35/78 35/78 U A61P 17/00 A61P 17/00 (72) Inventor Hayashi Yoshito Tokushima 2-26-204 Higashiyoshino-cho, Tokushima-shi (72) Inventor Hitoshi Ohno 1 at 13 South Takashima, Naruto-cho, Naruto-shi, Tokushima Prefecture (72) Inventor Shigetsugu Oyasu 1-1-27 Kitakoshitani, Koshigaya-shi, Saitama Prefecture (56) References JP-A-59-67215 (JP, A) JP-A-59-67211 (JP, A) JP-A-59-67212 (JP, A) JP-A-57-42621 (JP, A) JP-A-57 -136509 (JP, A) JP-A-3-291207 (JP, A) JP-A 61-30509 (JP, A) JP-A 64-40411 (JP, A) (58) Fields investigated (Int.Cl) .7, DB name) A61K ⁷ /00-7/50 A61K 31/17 A61K 31/575 A61P 17/00 CA (STN)

Claims (2)

(57) [Claims] 1. Urea 8-23% by weight and γ-derived from rice bran crude oil
Purification obtained by purifying oryzanol as a urea adduct
An external preparation for skin, which comprises γ-oryzanol and 0.5-5% by weight of purified γ-oryzanol having a ferulic acid ester content of phytosterols of 20% or more as an essential component. 2. The purified γ-oryzanol content is 1-4% by weight.
The external preparation for skin according to claim 1, which is