JP2860902B2 - External preparation for skin - Google Patents

Description

Description: FIELD OF THE INVENTION The present invention relates to an external preparation for skin, and more particularly, it is effective for the prevention and treatment of skin pigmentation, and when used in combination with various active ingredients, has an effect. And to provide a skin external preparation excellent in stability and safety.

[Prior art] Staining, freckles and pigmentation after sunburn are caused by the remarkable progression of melanin production by the activation of pigment cells (melanocytes) present in the skin. It is one.

External preparations containing ascorbic acid, hydrogen peroxide, glutathione, colloidal sulfur and the like, and hydroquinone in Europe and the United States are known for the purpose of preventing and improving these skin pigment problems.

Also, in response to various changes caused by sunburn, for example, there is an interest in wound healing effect, beautiful skin effect, anti-inflammatory effect, and improvement in feel.

[Problems to be solved by the invention] However, regarding the prevention and improvement of skin pigmentation,
Ascorbic acids are easily oxidized and unstable in a system containing a large amount of water, such as a water-containing cosmetic, and cause discoloration. In addition, hydrogen peroxide has problems in storage stability and safety, and glutathione and colloidal sulfur emit a remarkable off-odor, so that their use in products is restricted. Furthermore, hydroquinone has problems in safety, such as skin irritation and allergicity, and at present, satisfactory products have not yet been obtained.

The present invention has been made in view of the above circumstances, and not only exerts an excellent effect on the prevention and improvement of skin pigmentation, it is stable in a product, and is safe without harm to the skin. An object of the present invention is to provide a skin external preparation that can be used for skin.

In addition, a material that enhances wound healing, a material that has the effect of improving acne and improving skin moisture, a material that enhances the effect of anti-inflammatory agents, and a material that reduces the sticky feeling of moisturizers are added to the skin external preparation. Another object of the present invention is to exert a remarkable effect by utilizing the characteristics.

[Means for Solving the Problems] The present inventors have made intensive studies to solve the above problems, and as a result, resorcin glycosides have a remarkable melanin production inhibitory action, and are stable and highly safe. The present invention was found to be a compound, and based on this, the present invention was completed.

That is, the present invention is a skin external preparation characterized by containing a resorcin glycoside represented by the following general formula (I), In a preferred embodiment, the skin external preparation is characterized in that the blending ratio of the resorcin glycoside is 0.05 to 20% by weight of the whole.

Further, as a preferred embodiment, resorcin glycoside,
In combination with 0.01 to 5% by weight of a sun protection agent, or in combination with 0.01 to 5% by weight of a wound healing agent, or in combination with 0.01 to 5% by weight of a metabolic promoter, or anti-inflammatory An external preparation for skin, characterized in that it is used in combination with 0.01 to 5% by weight of an agent, or 0.1 to 20% by weight of a humectant, or a combination thereof.

 Hereinafter, the present invention will be described in detail.

The sugar residue of the resorcin glycoside applied to the present invention,
L-arabinose, L-xylose, D-ribose, L
-A residue of a pentose such as lyxose, D-glucose, D-
Galactose, L-galactose, D-mannose, D
-Residues of hexoses such as talose and D-fructose,
Glucosamine, D-galactosamine, residues of amino sugars such as sialic acid, D-glucuronic acid, D-galacturonic acid,
D-Residue of uronic acid such as mannuronic acid. From the viewpoints of whitening effect, availability, stability and safety, D
-Glucose residues are preferred.

Examples of the resorcin glycoside according to the present invention include m-hydroxyphenyl-β-D-glucoside and m-hydroxyphenyl-β-D-glucoside.
Examples include, but are not limited to, hydroxyphenyl-D-glucosaminide.

The mixing ratio of the resorcin glycoside used in the present invention is:
0.05-20% by weight of the whole is preferred.

That is, when used in an external preparation for skin such as cosmetics for the purpose of preventing spots, freckles, and darkness due to sunburn, 0.05% by weight or more, and an external preparation as a drug for the treatment of pigmentation disease When used in an amount of 1% by weight or more, it can be used as an effective amount. 0.01% used
If the concentration is lower, the object of the present invention cannot be achieved, and if it exceeds 20%, it may be unfavorable from the viewpoint of skin safety.

Next, various experiments were performed to evaluate the usefulness of the resorcin glycoside applied to the present invention.

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

Experimental Example 1 melanogenesis inhibition test (METHODS) plastic culture flasks (25 cm ²⁾ to 10 ⁵ B-16
The melanoma cells were seeded and cultured in RPMI 1640 medium containing 10% serum at 37 ° C. under 5% carbon dioxide. Five days later, m-hydroxyphenyl-β-D-glucoside was added at a concentration of 0.1, 1.0, and 2.0 mM in the medium, and the cells were further cultured for four days. After the culture, the medium was removed, and after washing with a phosphate buffer, the cells were collected in a glass centrifuge tube with rubber police and centrifuged at 1000 rpm. After washing the cells twice with a phosphate buffer, 1N sodium hydroxide was added to the sediment and dissolved by heating. After cooling, chloroform was added, followed by centrifugation again.
The resulting supernatant was measured at an absorbance of 400 nm,
The amount of melanin was determined from a calibration curve previously prepared using synthetic melanin. Incidentally, melanin amount was determined as the amount per 10 ⁶ cells.

(Result) As is clear from the results in Table 1, m-hydroxyphenyl-β-D-glucoside has a remarkable melanin-suppressing effect on melanoma cells.

Next, the stability of the resorcin glycoside and the skin external preparation containing the same are tested.

Experimental Example 2 Stability test (Method) 0.1% by weight of m-
Prepare a hydroxyphenyl-β-D-glucoside solution and a resorcinol solution as a control. After storing at 37 ° C. for 3 months together with the cream of Example 1 described below, the degree of coloring was evaluated with the naked eye.

(Evaluation) ◎: Little coloring ○: Slight coloring △: Coloring (Result) As is clear from the results in Table 2, m-hydroxyphenyl-β-D-glucoside alone is stable.

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

Next, the resorcin glycoside and the skin external preparation containing the same are tested for safety.

Experimental Example 3 Safety test (i) Cumulative skin irritation (Method) The back of a white guinea pig (5 animals in each group) was shaved using an electric clipper and washed with a disinfecting solution.

1 of m-hydroxyphenyl-β-D-glucoside
%, 5%, 10% ethanol-water (1: 1) solution and 4 samples of the cream of Example 1 described later, 50 mg once a day each
/ cm ^{2 was} applied and the degree of irritation was measured visually every day.

(Result) As is evident 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 (the cream of Example 1) also caused skin irritation. It is clear that there is no security.

(Ii) Contact sensitization (method) Using a healthy guinea pig weighing 380 to 420 g, the sensitization was performed according to the method of Sato et al. (See Contact Dermatitis, 7 , 225 (1981)).

(Samples) Three samples of m-hydroxyphenyl-β-D-glycoside, resorcinol as a control, and the cream of Example 1 of the present invention described later.

(Judgment criteria) (Result) As is clear from the results in Table 4, the strength of the contact sensitization was resorcin >> m-hydroxyphenyl-β-D-
Glucoside—the cream of Example 1.

m-Hydroxyphenyl-β-D-glucoside alone and the product of the present invention are safe without contact sensitization.

Next, the ultraviolet protective agent applied to the present invention, ascorbic acid or a derivative thereof, isoferulic acid or a salt thereof,
Glutathione or a derivative thereof, oxybenzone or a derivative thereof, p-aminobenzoic acid or a derivative thereof, urocanic acid or a derivative thereof, cinnamic acid or a derivative thereof, kojic acid, one or more kinds selected from titanium oxide and the like, The mixing ratio is 0.01 to 5% by weight of the whole.

By using resorcin glycoside in combination with the present ultraviolet protective agent, a remarkable healing-promoting effect is recognized for patients with color deposition due to the synergistic effect.

The wound healing agent applied to the present invention is one or more selected from toki extract, allantoin or a derivative thereof, rosemary extract, and the like, and the blending ratio is 0.01 to 5% by weight of the whole. .

By using the resorcin glycoside in combination with the present wound healing agent, the healing of the wound surface can be remarkably enhanced by the synergistic effect.

The metabolic promoter applied to the present invention is one or more selected from placenta extract (water-soluble placenta extract), γ-oryzanol, various amino acids, vitamin E or derivatives thereof, and the proportion thereof is It is 0.01 to 5% by weight of the whole.

The combined use of resorcin glycoside and the present metabolic promoter results in a synergistic effect that improves acne and improves skin moisturizing effect.

The anti-inflammatory agent applied to the present invention is one or two or more selected from glycyrrhetinic acid or a derivative thereof, glycyrrhizic acid or a derivative thereof, bisabolol, geraniin, malonier extract, aloe extract, and the like, and the mixing ratio thereof Is 0.01 to 5% by weight of the whole.

The combined use of resorcin glycoside and the present anti-inflammatory agent can increase the anti-inflammatory effect due to the synergistic effect.

The humectant applied to the present invention is one or two selected from hyaluronic acid or a salt thereof, glycosphingolipid, collagen, elastin, mucin, somaria, royal jelly, sodium casein, lecithin, chitin or chitosan or a derivative thereof. At least 0.1% by weight of the total.

By using the resorcinol glycoside and the present humectant in combination, it is possible to improve the feeling of use having a strong sticky feeling inherent to the humectant.

In addition, the skin external preparation of the present invention includes various components usually used in cosmetics, pharmaceuticals, and the like, that is, an aqueous component, an oily component, a surfactant, a powder component, a thickener, a pigment, a preservative,
Antioxidants, fragrances and thymus extracts, hormones, nucleic acids,
Various medicinal ingredients such as vitamins and pantethine can be blended. Of course, these can be used within a quantitative and qualitative range that does not impair the effects of the present invention.

Further, the dosage form of the external preparation for skin of the present invention is arbitrary, and any dosage form may be used as long as it is conventionally used for this type of external preparation for skin, for example, ointments, creams, emulsions, lotions and the like. Can be

EXAMPLES Hereinafter, the present invention will be described with reference to Examples and Comparative Examples, but the present invention is not limited to these Examples. In addition, the compounding amount is a weight part.

Examples 1 to 6 Cream (Preparation) As shown in Table-5.

(Manufacturing method) A and B are uniformly dissolved at 70 ° C. with stirring.

 B is gradually added to A with stirring.

Furthermore, after homogenizing uniformly with a homomixer, 70 ° C for a while
After cooling to 30 ° C, fill in a container to obtain a product.

First, the effect of improving pigmentation is described.

(Samples) The cream of Example 1 containing the m-hydroxyphenyl-β-D-glucoside of the present invention, the cream of Example 2 in combination with the ultraviolet protective agent, and m-hydroxyphenyl-β-D-glucoside Comparative Example 1 containing no
4 shows four samples of the cream of Comparative Example 2 containing only the cream of Example 1 and the UV protection agent.

(Method) Forty female volunteers suffering from dark-black, spots, and freckles were divided into four groups with approximately the same degree of pigmentation,
Each of the above creams was used for a long period of three months.

Three months later, five beauty specialists evaluated the degree of improvement in darkness, spots, and freckles.

(Result) As is clear from the results in Table 6, the effect of improving pigmentation was as follows: Example 2> Example 1> Comparative Example 2> Comparative Example 1. It can be seen that the m-hydroxyphenyl-β-D-glucoside of the present invention has an effect of improving pigmentation, but the effect is further enhanced when used in combination with an ultraviolet ray protective agent.

No side effects were observed in any of the creams during the test period, and it was confirmed that the product of the present invention was safe for the skin.

 Next, the wound healing effect will be described.

(Sample) Cream of Example 1 containing m-hydroxyphenyl-β-D-glucoside of the present invention, cream of Example 3 using this in combination with a wound healing agent, and m-hydroxyphenyl-β-D -It is three samples of the cream of the comparative example 3 which mix | blended the wound healing agent without mix | blending glucoside.

(Method) 5 weeks old SD rats were preliminarily reared for 7 days after purchase
Forty animals are divided into four groups of ten animals each. The back of the rat is shaved using an electric clipper and cleaned with an antiseptic solution. afterwards,
Using a circular chisel (φ11 mm), create four skin missing lesions symmetrically along the midline. The first group was an untreated group, the second group was applied with the cream of Example 1 after observation once a day, and the third group was similarly coated with the cream of Example 3
The cream of Comparative Example 3 is applied to the fourth group. Application is 1
Once a day, it was 0.1 g per each damaged site.

The observation was performed once a day for the measurement of the wound area and the visual observation. The cure rate is determined by the following equation.

(Result) As is clear from the results in Table 7, the wound healing rate was Example 3> Example 1> Comparative Example 3> No treatment. It can be seen that the m-hydroxyphenyl-β-D-glucoside of the present invention has a wound healing effect, and that the effect is further improved when used in combination with a wound healing agent.

 Next, the beautiful skin effect will be described.

(Sample) The cream of Example 1 containing the m-hydroxyphenyl-β-D-glucoside of the present invention, the cream of Example 4 using the same in combination with a metabolic promoter, and m-hydroxyphenyl-β-D -Do not mix glucoside
It is three samples of the cream of the comparative example 4 which contains the metabolic accelerator.

(Method) 30 female volunteers with acne on their face
Acne was classified into three groups with approximately the same degree of acne.
The cream was used for a long period of time for months.

Three months later, five beauty specialists evaluated the improvement of acne and the degree of skin moisture.

(Evaluation criteria) (Result) As is clear from the results in Table 8, the degree of improvement of acne was as follows: Example 4> Comparative Example 4 ≒ Example 1, and the degree of moisture of the skin was Example 4> Example 1> Comparative Example 1. Was. When the m-hydroxyphenyl-β-D-glucoside of the present invention is used in combination with a metabolism promoter, a beautiful skin effect is remarkably recognized.

 Next, the quenching effect will be described.

(Sample) The cream of Example 1 containing the m-hydroxyphenyl-β-D-glucoside of the present invention, the cream of Example 5 using the same in combination with an anti-inflammatory agent, and m-hydroxyphenyl-β-D -It is three samples of the cream of the comparative example 5 which mix | blended the anti-inflammatory agent without mix | blending glucoside.

(Method) Thirty male volunteers in their 20s and 30s were divided into three groups, which were exposed to sunlight on the beach in summer for half a day. Each group of each of the creams of Examples 1 and 5 and Comparative Example 5 was continuously used for 5 days, and the anti-inflammatory effects were compared based on the satisfaction due to the reduction of hot flash due to sunburn.

(Result) As is clear from the results in Table 9, the degree of reduction in the hot flash feeling due to sunburn was: Example 5> Comparative Example 5 ≒ Example 1. The combined use of the m-hydroxyphenyl-β-D-glucoside of the present invention and an anti-inflammatory agent has a remarkable anti-inflammatory effect.

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

(Sample) The cream of Example 1 containing the m-hydroxyphenyl-β-D-glucoside of the present invention, the cream of Example 6 using the cream in combination with the moisturizer, and m-hydroxyphenyl-β-D-glucoside. It is three samples of the cream of Comparative Example 6 in which a humectant was blended without blending glucoside.

(Method) A practical use test of the usability (stickiness) of the creams of Examples 1 and 6 and the cream of Comparative Example 6 was conducted by 10 female beauty specialists.

(Evaluation criteria) (Result) As is clear from the results in Table 10, the usability (stickiness) was as follows: Example 1 <Example 6 <Comparative Example 6.

The combination use of the m-hydroxyphenyl-β-D-glucoside of the present invention and a humectant significantly improved the sticky feeling inherent to the humectant.

Example 7 Lotion (Preparation) Ethanol 10.0 Polyoxyethylene (50) hydrogenated castor oil 1.0 Methyl paraoxybenzoate 0.1 Flavor 0.1 Allantoin 0.5 Chitosan 0.5 Disodium edetate 0.1 m-Hydroxyphenyl-D-glucosaminide 7.0 Propylene glycol 5.0 Purified water 75.7 (Production method) At room temperature, solubilize all components uniformly with stirring.
Packed in a container to make a product.

Example 8 Pack Fee (Preparation) (Production method) A is dispersed and dissolved at room temperature. Add B to this and dissolve uniformly. Put it in a container to make it a product.

Example 9 Ointment (preparation) (Production method) A and B are each heated and stirred to be uniformly dispersed. B is gradually added to A with stirring. Cool to 30 ° C and pack into containers to produce product.

[Effects of the Invention] According to the present invention, a skin external preparation containing resorcin glycoside has a remarkable melanin production inhibitory effect, is excellent in stability, and has low skin cumulative irritation and contact sensitization. It exerts an excellent effect on the prevention and improvement of skin pigmentation.

In addition, the combined use of resorcin glycosides and an ultraviolet protective agent has a remarkable healing promoting effect on patients with pigmentation disease.

In addition, the combined use of resorcin glycosides and a wound healing agent significantly accelerates the healing speed of the wound surface due to the synergistic effect.

In addition, by using the resorcin glycoside and the metabolic accelerator in combination, the synergistic effect is shown to improve acne and to provide a beautiful skin effect due to skin moisture.

In addition, the combined use of resorcin glycoside and anti-inflammatory agent increases the anti-inflammatory effect due to the synergistic effect.

Furthermore, the combined use of the resorcin glycoside and the humectant significantly improves the usability (stickiness) inherent in the humectant.

──────────────────────────────────────────────────続 き Continuation of the front page (72) Inventor Hiroyuki Nakano 27-1 Takashimadai, Kanagawa-ku, Yokohama-shi, Kanagawa Prefecture Investigator in Yokohama Research Laboratory, Polar Chemical Industry Co., Ltd. Tamotsu Tominaga (56) References JP-A-61-236710 (JP) JP-A-61-236709 (JP, A) JP-A-2-49715 (JP, A) JP-A-61-200906 (JP, A) JP-A-1-308476 (JP, A) (58) Surveyed fields (Int. Cl. ⁶ , DB name) A61K 7/00 A61K 31/70 CA, REGISTRY (STN)

Claims (7)

(57) [Claims] 1. An external preparation for skin comprising a resorcin glycoside represented by the following general formula (I). (2) The compounding ratio of resorcin glycoside is 0.5% of the whole.
The external preparation for skin according to claim 1, wherein the amount is from 05 to 20% by weight. 3. The external preparation for skin according to claim 1, which contains 0.01 to 5% by weight of an ultraviolet ray protective agent. 4. The external preparation for skin 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 metabolic accelerator. 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 0.1-20% by weight of a humectant.