JPH041116A - Dermal drug for external use - Google Patents

Abstract

PURPOSE:To obtain a dermal drug for external use, containing a resorcin glycoside, having remarkable inhibitory action on formation of melanin, effective in preventing and treating skin pigmentation and excellent in stability and safety. CONSTITUTION:A dermal drug for external use is obtained by blending a resorcin glycoside expressed by the formula (R is pentose residue, hexose residue, amino sugar residue or uronic acid residue) in an amount of 0.05-20wt.% based on the whole. Furthermore, 0.01-5wt.% each of an ultraviolet ray protectant, a wound curing agent, a metabolic promoter, or an anti-inflammatory agent, or 0.1-20wt.% humectant is preferably used together or they are preferably combined and blended. In addition, various ingredients normally used in cosmetics, medicines, etc., are suitably blended and prepared into a formulation to afford the objective substance. The agent can be prepared in the form of an ointment, a cream, a milky lotion, a lotion, etc.

Description

Detailed Description of the Invention [Industrial Application Field] The present invention relates to a skin external preparation, and more specifically, it is effective for the prevention and treatment of skin pigmentation disorders, and its effects can be improved by using it in combination with various active ingredients. It is an object of the present invention to provide an external preparation for skin that can significantly increase the skin function and also has excellent stability and safety.

[Conventional technology] Pigmentation caused by age spots, freckles, and sunburn is caused by a significant increase in melanin production due to the activation of pigment cells (melanocytes) present in the skin, and is a common cause of skin concerns among middle-aged and elderly people. They are one.

For the purpose of preventing and improving these skin pigment problems, external preparations containing ascorbic acid, hydrogen peroxide, glutathione, colloidal sulfur, etc., and in Europe and America, hydroquinone, are known.

In addition, in response to various changes caused by sunburn, for example, there is interest in wound healing effects, skin beautification effects, anti-inflammatory effects, and improvement in texture.

[Problems to be Solved by the Invention] However, regarding the prevention and improvement of skin pigmentation, ascorbic acids are easily oxidized and unstable in systems containing a lot of water, such as water-containing cosmetics, and can cause discoloration. . Further, hydrogen peroxide has storage stability and safety issues, and glutathione and colloidal sulfur emit a significant odor, so their use in products is restricted.

Furthermore, hydroquinone has safety problems such as skin irritation and allergy, and the current situation is that a fully satisfactory product has not yet been obtained.

The present invention was made in view of such circumstances, and
The object of the present invention is to provide an external skin preparation that not only exhibits an excellent effect on the prevention and improvement of skin pigmentation, but also is stable in the product and can be used safely without any adverse effects on the skin.

Furthermore, our external skin preparations contain materials that enhance wound healing, materials that improve acne and increase skin moisture, materials that enhance the effects of anti-inflammatory agents, and materials that reduce the sticky feeling of moisturizers. The challenge was to make use of its characteristics to achieve remarkable effects.

[Means for Solving the Problems] As a result of extensive research to solve the above problems, the present inventors have found that resorcin glycosides have a remarkable melanin production inhibiting effect, are stable and highly safe. The present invention was completed based on this discovery.

That is, the present invention is a skin external preparation characterized by containing a resorcin glycoside represented by the following general formula (I), and in a preferred embodiment, the blending ratio of the resorcin glycoside is lower than the total O. , an external skin preparation characterized by an OS of ~20% by weight.

Furthermore, as a preferable embodiment, resorcinol glycosides are used in combination with 0.01 to 5% by weight of an ultraviolet protection agent, or #J (0.01 to 5% by weight of a reagent II) is used in combination. Or, use in combination with a metabolism promoter o, oi ~ 5% by weight, or use in combination with an anti-inflammatory agent 0.01 to 5% by weight, or use a moisturizer 0.1 to 20% by weight. This external skin preparation is characterized by being used together or by combining these.

The present invention will be described in detail below.

The sugar residue of the resorcinol glycoside applied to the present invention is L
-arabinose, xylose, D-lipose, L-
Residues of pentose sugars such as lyxose, D-glucose, D-galactose, L-galactose, D-mannose, D-
Residues of hexoses such as talose and D-fructose, residues of amino sugars such as D-glucosamine, D-galactosamine, and sialic acid, D-glucuronic acid, D-galacturonic acid, D
-Residues of uronic acid such as mannuronic acid, whitening effect,
D-glucose residues are particularly preferred in terms of ease of availability, stability, and safety.

Examples of resorcin glycosides according to the present invention include m-hydroxyphenyl-β-D-glucoside and m-human Oxyphenyl-D-glucosaminide.
It is not limited to these.

The blending ratio of the resorcinol glycoside used in the present invention is preferably 0.05 to 20% by weight of the total.

In other words, when used in external skin preparations such as cosmetics aimed at preventing spots, freckles, and dark skin due to sunburn, the amount is 0.051% or more, and when used in drugs intended for the treatment of pigmentation disorders. When used as an external preparation, an effective amount of 1% by weight or more can be used. Usage amount is 0.0
The objectives of the present invention can be achieved at concentrations lower than 1%;
%, it may be unfavorable from the viewpoint of skin safety.

Next, various experiments were conducted to evaluate the usefulness of resorcinol glycosides applied to the present invention.

First, the melanin production inhibiting effect of Kawara-hydroxyphenyl-β-D-glucoside, which is an example of resorcin glycoside, was tested.

Experimental Example 1 Melanin production suppression test (method) 105 B-16 melanoma cells were seeded in a plastic culture flask (25 caf) and incubated in RPH11640 medium containing 10% serum, 5% carbon dioxide, and 31°C. cultivated under. 5 days later m-hydroxyphenyl β-
D-glucoside was added to the medium at a concentration of 0.1. 1.0゜2
．． The cells were added at a concentration of 0 mA and cultured for an additional 4 days.

After culturing, the medium was removed, and after washing with phosphate buffer, the cells were collected in a glass centrifuge tube using rubber police and centrifuged at 1000 rpm. After washing the cells twice with phosphate buffer, 1N sodium hydroxide was added to the precipitate and dissolved by heating. After cooling, chloroform was added and centrifuged again. The absorbance of the supernatant thus obtained was measured at 400 nm, and the amount of melanin was determined from a calibration curve prepared in advance using synthetic melanin. In addition, the amount of melanin was determined as the amount per 106 cells.

(Margin below) (Result) After being stored for 3 months, the degree of coloring was evaluated with the naked eye.

(Evaluation) ◎: Almost no coloration O: Mild coloration △: Coloration (Results) As is clear from the results in Table 1, m-hydroxyphenyl-β-D-glucoside has an effect on melanoma cells. It shows a remarkable melanin suppressing effect on the skin.

Next, the stability of resorcinol glycosides and external skin preparations containing them will be tested.

Experimental Example 2 Stability Test (Method) A 0.19% by weight m-hydroxyphenyl-β-D-glucoside solution and a resorcinol solution as a control were prepared in a 0.1N aqueous sodium hydroxide solution. Make l. As is clear from the results in Table 2 at 37°C, m-hydroxyphenyl-β-D-glucoside alone is stable together with the cream of Example 1 described below.

Furthermore, it can be seen that the skin external preparation of the present invention (the cream of Example 1) is also stable.

Next, the safety of resorcinol glycosides and external skin preparations containing the same will be tested.

Experimental Example 3 Safety Test (i) Cumulative Skin Irritation (Method) Hair is removed from the backs of white guinea pigs (5 animals in each group) using electric clippers and washed with a disinfectant solution.

1% of m-hydroxyphenyl-β-D-glucoside,
5%, io% ethanol-water (1:1) solution and four samples of the cream of Example 1 described below, each 5O! ! tg/cd was applied, and the degree of irritation was visually measured every day.

(Results) As is clear from the results in Table 3, m-hydroxyphenyl-β-D-glucoside did not cause skin irritation at any concentration, and the skin external preparation of the present invention (cream of Example 1) The results show that it is safe and does not cause any skin irritation.

(11) Contact sensitization (method) Healthy guinea pigs with body sizes of 1380 to 4209 were used, and the method of Sahara et al.
, 7. 225 (1981).

(Samples) These are three samples of m-hydroxyphenyl-β-D-glycoside, resorcinol as a control product, and cream of Example 1 of the present invention described below.

(Judgment criteria) (Left below) Formation of erythema and near skin (Results) Table 4 Formation of contact sensitizing edema As is clear from the results in Table 4, the strength of contact sensitization is Zorcin〉〉Hydroxyphenyl-β-D-
Glucoside → Cream of Example 1.

Neither m-hydroxyphenyl-β-D-glucoside alone nor the product of the present invention exhibits contact sensitization and is safe.

(The following is a blank space) Next, the ultraviolet protection agent applied to the present invention includes ascorbic acid or its derivatives, isoferulic acid or its salts, glutathione or its derivatives, oxybenzone or its derivatives, p-aminobenzoic acid or its derivatives. , urocanic acid or its derivatives, cinnamic acid or its derivatives, kojic acid, titanium oxide, etc., and
The blending ratio thereof is 0.01 to 5% by weight of the total.

By using resorcinol glycosides and the present ultraviolet protection agent in combination, their synergistic effect results in a remarkable healing promoting effect on patients with pigmentation disorders.

The wound healing agent applied to the present invention is one or more selected from Toki extract, allantoin or its derivatives, rosemary extract, etc., and the blending ratio thereof is 0.01 to 5% by weight of the total. It is.

By using resorcinol glycosides and the present wound healing agent together, their synergistic effect can significantly enhance the healing of the wound surface.

The metabolism promoter applied to the present invention is placenta extract (
Water-soluble placenta extract, ), γ-oryzanol, various amino acids, vitamin E or its derivatives, etc., and their proportion is 0.01 to 5% of the total.
Weight%.

When resorcinol glycosides and the present metabolism promoter are used in combination, their synergistic effect improves acne and moisturizes the skin, resulting in beautifying skin.

The anti-inflammatory agent applied to the present invention is one or more selected from glycyrrhetinic acid or its derivatives, glycyrrhizic acid or its derivatives, bisabolol, geraniin, horse chestnut extract, aloe extract, etc., and the blending ratio thereof is 0.01 to 5% by weight of the total.

By using resorcinol glycosides and the present anti-inflammatory agent in combination, the anti-inflammatory effect can be increased due to their synergistic effect.

The moisturizers applied to the present invention include hyaluronic acid or its salts, glycosphingolipids, collagen, elastin, mucin, sour cream, royal jelly caseinate sodium,
It is one or more selected from lecithin, chitin, chitosan, and derivatives thereof, and the proportion thereof is 0.1 to 201% of the total.

By using resorcin glycosides and this moisturizer together,
It is possible to improve the strong sticky feel inherent in moisturizers.

In addition, the skin external preparation of the present invention includes various components 1 commonly used in cosmetics, pharmaceuticals, etc., namely, aqueous components, oily components, surfactants, powder components, thickeners, pigments, preservatives,
Antioxidants, fragrances and thymus extract, hormones, nucleic acids,
Medicinal ingredients such as various vitamins and pantethine can be added. Of course, these can be used within a quantitative and qualitative range that does not impair the effects of the present invention.

Furthermore, the dosage form of the skin external preparation of the present invention is arbitrary and may be any of those conventionally used for this type of skin external preparation, such as ointments, creams, milky lotions, and lotions. It will be done.

[Examples] The present invention will be explained below using Examples and Comparative Examples, but the present invention is not limited to these Examples.

In addition, the blending amount is in parts by weight.

Examples 1-6 Cream ('2a) As shown in Table-5.

(Production method) Uniformly dissolve A and B at 70°C while stirring each.

Gradually add B to A while stirring.

Furthermore, after uniformly emulsifying with a homomixer, it was heated to <70℃ for a while.
After cooling to 30'C, it is packed in a container and used as a product.

(Margin below) First, we will discuss the pigmentation improvement effect.

(Sample) The cream of Example 1 containing the roof tile-hydroxyphenyl-β-D-glucoside of the present invention, the cream of Example 2 using a UV protection agent in combination, and m-hydroxyphenyl-β-D-glucoside These are four samples of the cream of Comparative Example 1, which does not contain UV protection agent, and the cream of Comparative Example 2, which contains only UV protection agent.

(Method) Forty female volunteers suffering from dark skin, age spots, and freckles were divided into four groups with statistically equal levels of pigmentation.
Each subject used the above cream for a long period of time for 3 months.

Three months later, five beauty experts evaluated the degree of improvement in dark skin, age spots, and freckles.

(Results) Table 6 Pigmentation improvement effect As is clear from the results in Table 6, the pigmentation improvement effects were as follows: Example 2>Example 1>Comparative Example 2>Comparative Example 1. It can be seen that the kawara-hydroxyphenyl-β-D-glucoside of the present invention has an effect of improving pigmentation, and that the effect is further enhanced when used in combination with an ultraviolet protection agent.

Furthermore, no side effects were observed in any of the creams during the test period, confirming that the products of the present invention are safe for the skin.

Next, the wound healing effect will be described.

(Samples) The cream of Example 1 containing m-hydroxyphenyl-β-D-glucoside of the present invention, the cream of Example 3 containing this in combination with a wound healing agent, and m-hydroxyphenyl-β-D - Three samples of the cream of Comparative Example 3 in which a wound healing agent was blended without glucoside.

(Method) Forty 5-week-old SD rats were preliminarily bred for 7 days after purchase and divided into 4 groups of 10 rats each. Hair is removed from the back of the rat using electric clippers and cleaned with disinfectant solution. Then, using a circular chisel (φ11M), four skin defects are created symmetrically along the midline. The first group was treated as an untreated group, the second group was treated with the cream of Example 1 once a day after the observation, and similarly, the cream of Example 3 was applied to the third group, and the comparative example was applied to the fourth group. Apply cream from step 3. Application was once a day at 0.19 per injury site.

In addition, the wound area was measured and visually observed once a day. The healing rate is calculated using the following formula.

(Area of the wound on day 0) Wound area on the 11th day Healing rate (%) = (Result) As is clear from the results of wound area table 7 on day 0, the wound healing rate was Example 3〉Example 1〉Comparative Example 3〉No treatment. It can be seen that the m-hydroxyphenyl-βD-glucoside of the present invention has a wound therapeutic effect, and its effect is further improved when used in combination with a wound healing agent.

Next, we will discuss the skin beautifying effect.

(Samples) The cream of Example 1 containing m-hydroxyphenyl-β-D-glucoside of the present invention, the cream of Example 4 containing m-hydroxyphenyl-β-D-glucoside in combination with a metabolism promoter, and m-hydroxyphenyl-β-D-glucoside. - Three samples of the cream of Comparative Example 4, which did not contain glucoside but contained a metabolism promoter.

(Method) Thirty female volunteers with acne on their faces were
Divided into 3 groups with statistically equivalent levels of acne;
The above cream was used for a long period of time for several months.

Three months later, five beauty experts evaluated the improvement in acne and the level of moisture in the skin.

(Evaluation criteria) Skin beautification effect evaluation score (Results) As is clear from the results in Table 8, the degree of improvement in acne was
Example 4> Comparative Example 4 Cape Example 1, and the skin moisture level was Example 4> Example 1> Comparative Example 1. By using the m-hydroxyphenyl-β-D-glucoside of the present invention in combination with a metabolism promoter, a remarkable skin beautifying effect is observed.

Next, we will discuss the anti-inflammatory effect.

(Samples) The cream of Example 1 containing m-hydroxyphenyl-β-D-glucoside of the present invention, the cream of Example 5 containing this in combination with an anti-inflammatory agent, and m-hydroxyphenyl-β-D - Three samples of the cream of Comparative Example 5, which contains no glucoside but contains an anti-inflammatory agent.

(Method) Thirty male volunteers in their 20s to 30s were divided into three groups and exposed to sunlight for half a day at a summer beach. The creams of Example 1.5 and Comparative Example 5 were used in each group for 5 days, and the anti-inflammatory effects were compared based on the feeling of satisfaction due to the reduction in the feeling of hot flashes caused by burns.

(Results) As is clear from the results in Table 9, the degree of reduction in the feeling of hot flashes due to sunburn was that of Example 5>Comparative Example 5 and Example 1. A remarkable anti-inflammatory effect was observed when the m-hydroxyphenyl-β-D-glucoside of the present invention was used in combination with an anti-inflammatory agent.

Next, the effect of improving the feeling of use will be described.

(Samples) The cream of Example 1 containing m-hydroxyphenyl-β-D-glucoside of the present invention, the cream of Example 6 containing this in combination with a moisturizer, and m-hydroxyphenyl-β-D - Three samples of the cream of Comparative Example 6 in which a humectant was blended without glucoside.

(Method) Ten female beauty experts conducted a practical use test for the usability (stickiness) of the cream of Example 1.6 and the cream of Comparative Example 6.

(Evaluation Criteria) (Results) As is clear from the results in Table 10, the usability (stickiness) was that of Example 1, Example 6, and Comparative Example 6.

By using the m-hydroxyphenyl-β-D-glucoside of the present invention in combination with a humectant, the sticky feeling inherent in the humectant could be significantly improved.

Example 7 Lotion (prescription) Ethanol 10.0 Polyoxyethylene (50) Hydrogenated castor oil 1.0 Methyl roseoxybenzoate 0.1 Fragrance
0.1 Allantoin 0.
5 Chitosan 0.5 Disodium edetate o,im-Hydroxyphenyl-[)-7,0 Glucosaminidopropylene glycol 5.0 Purified water 75.7 (Manufacturing method) At IF, homogenize all ingredients while stirring. Solubilize in. Pack it into a container and use it as a product.

(Left below) Example 8 Packing material Example 9 Ointment (prescription) (Production method) Disperse and dissolve A at 7 temperatures. Add B to this and dissolve uniformly. Pack it into a container and use it as a product.

(Production method) Heat and stir each of A and B to uniformly disperse them.

Gradually add B to A while stirring. Cool to 30°C and pack into a container to make the product.

[Effects of the Invention] According to the present invention, a skin external preparation containing a resorcinol glycoside has a remarkable effect of inhibiting melanin production, has excellent stability, and has low cumulative skin irritation and contact sensitization. It is highly effective in preventing and improving skin pigmentation.

Moreover, the combined use of resorcinol glycosides and UV protection agents has a significant healing promoting effect on patients with hyperpigmentation.

Furthermore, by using resorcinol glycosides and a wound healing agent in combination, their synergistic effect significantly accelerates the healing speed of the wound surface.

Furthermore, by using resorcinol glycosides and a metabolism promoter in combination, their synergistic effect improves acne and moisturizes the skin, resulting in beautifying skin.

Further, by using resorcinol glycosides and an anti-inflammatory agent together, the synergistic effect increases the anti-inflammatory effect.

Furthermore, by using resorcinol glycosides and a humectant in combination, the usability (sticky feeling) inherent in humectants is significantly improved.

Claims (1)

[Scope of Claims] 1) An external skin preparation characterized by containing a resorcinol glycoside represented by the following general formula (I). ▲There are mathematical formulas, chemical formulas, tables, etc.▼ (I) (R in the formula indicates pentose residue, hexose residue, amino sugar residue, uronic acid residue, etc.) 2) Resorcin glycoside The proportion of the body is 0.05~
The skin external preparation according to claim (1), which contains 20% by weight. 3) The skin preparation for external use according to claim 1, which contains 0.01 to 5% by weight of a UV protection agent. 4) The skin external preparation according to claim 1, which contains 0.01 to 5% by weight of a wound healing agent. 5) The external preparation for skin according to claim 1, which contains 0.01 to 5% by weight of a metabolism promoter. 6) The external preparation for skin according to claim 1, which contains 0.01 to 5% by weight of an anti-inflammatory agent. 7) The external preparation for skin according to claim 1, which contains 0.1 to 20% by weight of a humectant.