JPH0987164A - Skin preparation for external use - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a skin preparation for external use suitable for lightening skin and preventing aging, excellent in inhibitory action on tyrosinase activity and promoting action on collagen production. SOLUTION: This skin preparation for external use contains 0.0005-20wt.%, preferably 0.001-10wt.% calculated as a dried substance of an extract of a plant of Pule and/or Uret-uret growing in a dry meadow, pasture, etc., especially in Indonesia. The extract of Pule and/or Uret-uret is obtained by immersing leaves, stems, flowers, bark, seeds. fruits, the whole plant of Pule and/or Uret- uret in an extractive solvent (e.g. solvent) or heating under reflux, filtering and concentrating. The extract is properly mixed with conventional additives and can be prepared into an ointment, cream, milky lotion, pack, bathing agent, etc. The skin preparation for external use has excellent effects on pigmentation after suntan, stain, freckles, lightening such as chloasma and lightening skin, maintains lively skin free from wrinkle and slack, etc., prevents skin aging and can retain young skin.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention has an effect of inhibiting tyrosinase activity which is effective for preventing and improving pigmentation, spots, freckles, chloasma, etc. after sunburn by incorporating an extract of a specific plant. The present invention relates to an external preparation for skin which has an excellent effect of whitening the skin and can enhance the collagen-producing ability of the skin to prevent aging of the skin.

[0002]

BACKGROUND OF THE INVENTION Although there are some unclear points about the mechanism of the generation of skin spots and the like, it is generally caused by hormonal abnormalities and irritation of ultraviolet rays from sunlight. It is believed that melanin pigment is formed, which is abnormally deposited in the skin. This melanin pigment, which causes skin coloring, is produced in the melanin-producing granules (melanosomes) in the melanocytes (melanocytes) between the epidermis and the dermis, and the produced melanin diffuses into adjacent cells by osmotic action. . The biochemical reaction in this melanocyte is presumed to be as follows.

That is, tyrosine, which is an essential amino acid, is converted into dopaquinone by the action of the enzyme tyrosinase, which is converted into black melanin via a red pigment and a colorless pigment by an enzymatic or non-enzymatic oxidative action in the process of producing melanin pigment. is there. Therefore, it is important to suppress the action of tyrosinase, which is the first step of the reaction, to suppress melanin production.

However, the compounds that suppress the action of tyrosinase, except for hydroquinone, exhibit their effects very slowly, so that the effect of improving skin pigmentation is not sufficient. On the other hand, although hydroquinone is recognized as having an effect, its use is generally restricted because of its sensitizing properties. Therefore, in order to improve its safety, attempts have been made to use higher fatty acid monoesters or alkyl monoethers (JP-A-58-154507), but the esters are decomposed by a hydrolase in the body. Therefore, it is not always safe, and ethers have not been sufficiently satisfactory in terms of safety.

On the other hand, research on aging has been advanced in recent years,
As a cause of skin aging, aging is an important factor from a macro perspective, and dryness, oxidation, and the effects of sunlight (ultraviolet rays) have been cited as direct factors related to skin aging. Specific phenomena of skin aging include collagen cross-linking reaction, reduction of mucopolysaccharides such as hyaluronic acid, damage to cells by ultraviolet rays, etc., but mucopolysaccharides like conventional cosmetics are known. It has also become clear that aging of the skin cannot be adequately prevented simply by blending biochemical products such as collagen and collagen and synthetic polymer products to maintain moisture.

Therefore, it works on fibroblasts in the skin,
By promoting the biosynthesis of collagen, which is one of the important components of the dermis, a collagen production promoter capable of preventing skin aging and having no problem in terms of safety has been desired. As a component having such a collagen production promoting action, the present inventors have found an enzyme obtained by treating an alkaline extract of low-allergen rice obtained by previously treating rice with a proteolytic enzyme with the enzyme. Decomposed products are known (Japanese Patent Application No. 7-243463, Japanese Patent Application No. 8-976).
No. 54). Further, a further substance having an excellent ability to promote collagen production has been desired.

[0007]

As a solution to these problems, the present inventors have investigated a wide variety of substances for their ability to inhibit tyrosinase activity and ability to promote collagen production, and as a result, specific plant extracts were found to be excellent. They found that they have a tyrosinase activity inhibitory action and a collagen production promoting action, and completed the present invention. There has been no report about the tyrosinase activity inhibitory action of the extracts of these plants described below, and the application to skin whitening agents and anti-aging agents has been unknown, and the application to external skin preparations has not been known at all. The present inventors have completed the present invention based on the above findings.

That is, the present invention is an external preparation for skin, which comprises one or more selected from the following plant extracts. (1) Pule (scientific name: Alstonia scholaris) (2) Uret-uret (scientific name: Helicter
es ixora L.)

The external preparation for skin of the present invention is preferably a tyrosinase inhibitor or an anti-aging agent, and the anti-aging agent is preferably a collagen production promoter among them.

The structure of the present invention will be described in detail below. Plants used in the present invention are plants that grow on dry grasslands, pastures and the like in Indonesia. The extract used in the present invention is obtained by immersing or heating and refluxing the above-mentioned plant leaves, stems, flowers, bark, seeds or fruits, whole plant, etc. together with an extraction solvent, followed by filtration and concentration. The extraction solvent used in the present invention may be any solvent that is generally used for extraction, and in particular, alcohols such as methanol and ethanol,
Organic solvents such as hydrous alcohols, acetone and ethyl acetate can be used alone or in combination.

The amount of the plant extract compounded in the present invention is
It is 0.0005 to 20.0% by weight, preferably 0.001 to 10.0% by weight as a dry matter in the total amount of the external preparation.
If the amount is less than 0.0005% by weight, the effects of the present invention cannot be sufficiently exerted, and if it exceeds 20.0% by weight, it is difficult to formulate the composition, which is not preferable. Further, even if the content is 10.0% by weight or more, the effect is not so much improved.

The external preparation for skin of the present invention contains, in addition to the above-mentioned essential components, components usually used in external preparations for skin such as cosmetics and pharmaceuticals, for example, other whitening agents, moisturizers, antioxidants and oily ingredients. , UV absorber, surfactant, thickener,
Alcohols, powder components, coloring agents, aqueous components, water, various skin nutrients and the like can be appropriately added as necessary.

In addition, sequestering agents such as disodium edetate, trisodium edetate, sodium citrate, sodium polyphosphate, sodium metaphosphate, gluconic acid, caffeine, tannin, verapamil, tranexamic acid and its derivatives, licorice extraction Substance, glabridin, hot water extract of karin fruit, various herbal medicines, drugs such as tocopherol acetate, glycyrrhizic acid and its derivatives or salts thereof, vitamin C, magnesium ascorbyl phosphate, ascorbyl glucoside, arbutin, kojic acid, etc. Other whitening agents, sugars such as glucose, fructose, mannose, sucrose, trehalose and the like can also be appropriately added.

The external preparation for skin of the present invention may be any ointment, cream, emulsion, lotion, pack, bath agent or the like as long as it has been conventionally used for external preparations for skin, and its dosage form is not particularly limited.

[0015]

Next, the present invention will be described in more detail by way of examples. The present invention is not limited to this. The blending amount is% by weight. Prior to the Examples, a test method and results of the tyrosinase activity inhibitory effect and the collagen production promoting effect of the plant extract of the present invention will be described.

Tyrosinase activity inhibitory effect 1. Sample preparation

(1) Pre-Pule Extraction Solution 50 g of pre-pure bark was immersed in ethanol at room temperature for 1 week, and the extraction solution was concentrated to obtain 1.1 g of an ethanol extract. Dissolve this extract in DMSO 1%,
This solution was diluted to adjust the concentration, and the following experiment was conducted using this solution.

(2) Uret-uret extract 50 g of Uret-uret fruit
Was immersed in ethanol at room temperature for 1 week and the extract was concentrated to obtain 0.2 g of an ethanol extract. This extract is D
After dissolving 1% in MSO and diluting this solution to adjust the concentration, the following experiment was performed using this.

2. Test Method and Results (1) Cell Culture Method Mouse-derived B16 melanoma cultured cells were used. 1
0% FBS and theophylline (0.09 mg / ml)
The cells were cultured in an Eagle MEM medium containing C. in a CO ₂ incubator (95% air, 5% carbon dioxide) at 37 ° C. After 24 hours of culture, the sample solution is added to a final concentration (concentration in terms of dry extract) of 10 ^-2 to 10 ^-5 % by weight, and the culture is further continued for 3 days, and the tyrosinase activity inhibitory effect is measured by the following method did.

(2) Measurement of tyrosinase activity Prior to measurement, the medium in the wells was removed, and the wells were washed twice with 100 μl of PBS. 45 μl of 1% Triton-X in each well
(Rohm and Haas product name, surfactant) containing PBS is added. Shake the plate for 1 minute, break the cell membrane well, and use a microplate reader for 475n.
The absorbance at m was measured, and this was taken as the absorbance at 0 minutes. Then, 5 μl of 10 mM L-DOPA solution was quickly added, and the mixture was transferred to an incubator at 37 ° C. and reacted for 60 minutes. The plate was shaken for 1 minute, and the absorbance (475 nm) at 60 minutes was measured. The tyrosinase activity ratio (%) was defined as the ratio of the absorbance difference of the sample with the plant extract to the absorbance difference between the time of 0 minute and the time of 60 minutes in the case of the sample to which no plant extract was added (control). Table 1 shows the results. In addition, as a reference example, the same test as described above was conducted on an ethanol extract of a scallop (Lamiaceae: Subfamily Lamiaceae) already known to have a tyrosinase activity inhibitory action. Table 1 also shows the results.
In addition, in the table, − indicates a risk rate of 5% as compared with the control.
It means that no significant difference was observed within.

[0021]

[Table 1] ───────────────────────────── Test tyrosinase activity (%) ─────────── ────────────── Concentration (wt%) 10 ^-5 10 ^-4 10 ^-3 10 ^-2 ─────────────────── ────────── Pre-extract 53 − − − Ure-Ure extract − − 71 67 Kaigai extract − − − 55 ───────────────── ─────────────

Collagen production promoting effect 1. Preparation of Samples Each sample was prepared in the same manner as in the tyrosinase activity inhibitory effect.

2. Cell Culture Method and Measurement of Collagen Production Acceleration Activity Human skin fibroblasts were seeded in a 96-well petri dish at 20,000 and 48
After culturing in RITC80-7 containing 10% FBS for a time, the medium was replaced with a medium containing 0.5% FBS, a plant extract dissolved in DMSO was added, and the cells were further cultured for 48 hours.
DMSO should be 1/200 (5 μl per 1 ml of medium)
l) Added. The extract concentration was 10 ⁻⁵ to 10 ⁻² wt%. After the culture, the medium was collected and used for collagen measurement.
Further, the amount of DNA in the petri dish was measured and used as an index of the cell number. The amount of DNA was measured by a fluorescence measurement method using H33258. For each plant extract, 10 ^-2
The cytotoxicity was observed in the case of 10% by weight, but no toxicity was observed in the case of 10 ^-3 % by weight. Therefore, a type I carboxyterminal propeptide (P) produced by cultured human dermal fibroblasts is used.
IP) was measured by ELISA, and the PIP amount of a sample with a plant extract added at a concentration of 10 ^-3 % by weight, assuming that the amount of PIP per DNA of the sample (control) to which no plant extract was added was 100. It was measured and defined as collagen production promotion rate (%). The results are shown in Table 2. In addition, as a reference example, the same test as described above was performed on a solvent extract of Rishimi, which is already known to have a collagen production promoting action. The results are also shown in Table 2.

[0024]

[Table 2] ───────────────────────────── Test Collagen production promoting effect (%) ────────── ──────────────────── Pre-extract 176.6 Ure-Ure extract 123.9 Hishimi extract 124.1 ───────── ────────────────────

Examples of blending various types of external preparations for skin according to the present invention will be described below as examples.

Example 1 Cream (Formulation) Stearic acid 5.0% by weight Stearyl alcohol 4.0 Isopropyl myristate 18.0 Glycerin monostearate 3.0 Propylene glycol 10.0 Premethanol extract 0.01 Caustic potash 0 .2 Sodium bisulfite 0.01 Preservative Suitable amount Perfume Suitable amount Ion-exchanged water Residual (production method) Dissolve propylene glycol, premethanol extract and caustic potash in ion-exchanged water and heat to 70
Keep at ℃ (water phase). Mix with other ingredients and heat and melt to 70
C (oil phase). The oil phase is gradually added to the water phase, and after the addition is completed, the temperature is maintained for a while to cause a reaction. Then, it is uniformly emulsified with a homomixer and cooled to 30 ° C. with thorough stirring.

Example 2 Cream (formulation) Stearic acid 2.0% by weight Stearyl alcohol 7.0 Hydrogenated lanolin 2.0 Squalane 5.0 2-Octyldodecyl alcohol 6.0 Polyoxyethylene (25 mol) cetyl alcohol ether 3.0 Glycerin monostearate 2.0 Propylene glycol 5.0 Ure-Ure ethanol extract 0.05 Sodium bisulfite 0.03 Ethylparaben 0.3 Perfume suitable amount Ion-exchanged water Residue (production method) Propylene in ion-exchanged water Add glycol,
Heat and maintain at 70 ° C. (aqueous phase). The other ingredients are mixed, heated and melted and maintained at 70 ° C. (oil phase). The oil phase is added to the aqueous phase to carry out preliminary emulsification, and the mixture is uniformly emulsified with a homomixer and then cooled to 30 ° C. with thorough stirring.

Example 3 Cream (Formulation) Solid paraffin 5.0% by weight Beeswax 10.0 Vaseline 15.0 Liquid paraffin 41.0 Glycerin monostearate 2.0 Polyoxyethylene (20 mol) sorbitan monolaurate 2 0.0 Soap powder 0.1 Borax 0.2 Preacetone extract 0.05 Ure-Ure ethanol extract 0.05 Sodium hydrogen sulfite 0.03 Ethylparaben 0.3 Perfume proper amount Ion-exchanged water Residual (production method) Ion-exchanged water Soap powder and borax are added to the mixture, heated and melted and kept at 70 ° C (aqueous phase). The other ingredients are mixed, heated and melted and maintained at 70 ° C. (oil phase). The oil phase is stirred into the water phase and gradually added to carry out the reaction. After the reaction is completed, the mixture is uniformly emulsified with a homomixer, and after emulsification, the mixture is cooled to 30 ° C. with thorough stirring.

Example 4 Emulsion (formulation) Stearic acid 2.5 wt% Cetyl alcohol 1.5 Vaseline 5.0 Liquid paraffin 10.0 Polyoxyethylene (10 mol) monooleate 2.0 Polyethylene glycol 1500 3. 0 Triethanolamine 1.0 Carboxyvinyl polymer 0.05 (trade name: Carbopol 941, BFGoodrich Chemical company) Pre-acetic acid ethyl ester extract 0.01 Sodium bisulfite 0.01 Ethylparaben 0.3 Perfume proper amount Ion-exchanged water Residual (manufacturing method) The carboxyvinyl polymer is dissolved in a small amount of ion-exchanged water (phase A). Polyethylene glycol 1500 and triethanolamine are added to the remaining ion-exchanged water, dissolved by heating, and kept at 70 ° C. (aqueous phase). The other ingredients are mixed, heated and melted and maintained at 70 ° C. (oil phase). The oil phase is added to the water phase to perform preliminary emulsification, the phase A is added, and the mixture is uniformly emulsified with a homomixer. After the emulsification, the mixture is cooled to 30 ° C. while stirring well.

Example 5 Emulsion (Formulation) Microcrystalline wax 1.0% by weight Beeswax 2.0 Lanolin 20.0 Liquid paraffin 10.0 Squalane 5.0 Sorbitan sesquioleate 4.0 Polyoxyethylene (20 mol) ) Sorbitan monooleate 1.0 Propylene glycol 7.0 Ure-uretone acetone extract 10.0 Sodium hydrogen sulfite 0.01 Ethylparaben 0.3 Perfume proper amount Ion-exchanged water Residual (production method) Add propylene glycol to ion-exchanged water ,
Heat and maintain at 70 ° C. (aqueous phase). The other components are mixed, heated and melted and kept at 70 ° C. (oil phase). While stirring the oil phase, the aqueous phase is gradually added thereto, and the mixture is uniformly emulsified with a homomixer. After emulsification, cool to 30 ° C with good stirring.

Example 6 Jelly (formulation) 95% ethyl alcohol 10.0% by weight dipropylene glycol 15.0 polyoxyethylene (50 mol) oleyl alcohol ether 2.0 carboxyvinyl polymer 1.0 (trade name: Carbopol) 940, BFGoodrich Chemical company) Caustic soda 0.15 L-Arginine 0.1 Pre 50% ethanol aqueous solution extract 7.0 2-Hydroxy-4-methoxybenzophenone sulfonate sodium 0.05 Ethylenediaminetetraacetate ・ 3 sodium ・ 2 water 0 .05 Methylparaben 0.2 Fragrance Appropriate amount Ion-exchanged water Residue (production method) Carbopol 940 was uniformly dissolved in ion-exchanged water, while pre-50% ethanol aqueous solution extract and polyoxyethylene (50 mol) oleyl was added to 95% ethanol. Alcohol ether Is dissolved and added to the aqueous phase. Next, after adding other components, the mixture is neutralized with caustic soda and L-arginine to increase the viscosity.

Example 7 Beauty Serum (Formulation) (Phase A) Ethyl Alcohol (95%) 10.0% by Weight Polyoxyethylene (20 mol) Octyldodecanol 1.0 Pantotenyl Ethyl Ether 0.1 Ure-uremethanol Extract 1.5 Methylparaben 0.15 (Phase B) Potassium hydroxide 0.1 (Phase C) Glycerin 5.0 Dipropylene glycol 10.0 Sodium bisulfite 0.03 Carboxyvinyl polymer 0.2 (trade name: Carbo Pole 940, BFGoodrich Chemical company) Purified water Residue (production method) Phases A and C are uniformly dissolved, and A is added to phase C
Add phase and solubilize. Next, after adding the phase B, filling is performed.

Example 8 Pack (formulation) (Phase A) Dipropylene glycol 5.0% by weight Polyoxyethylene (60 mol) hydrogenated castor oil 5.0 (Phase B) premethanol extract 0.01 Olive oil 5.0 Tocopherol acetate 0.2 Ethylparaben 0.2 Perfume 0.2 (Phase C) Sodium hydrogen sulfite 0.03 Polyvinyl alcohol 13.0 (Saponification degree 90, degree of polymerization 2,000) Ethanol 7.0 Purified water Residual (manufacturing method ) A phase, B phase, and C phase are uniformly dissolved,
Phase B is added to the phase to solubilize it. Next, this is added to the C phase and then filled.

Example 9 Solid foundation (formulation) Talc 43.1% by weight Kaolin 15.0 Sericite 10.0 Zinc white 7.0 Titanium dioxide 3.8 Yellow iron oxide 2.9 Black iron oxide 0.2 Squalane 8 0.0 Isostearic acid 4.0 POE sorbitan monooleate 3.0 Isocetyl octanoate 2.0 Ure-Ure ethanol extract 1.0 Preservative proper amount Perfume appropriate amount (Production method) Talc-black iron oxide powder component is sufficient with a blender After mixing, an oily component of squalane to isocetyl octoate, an ethanol extract of urea-urea, an antiseptic and a fragrance are added and kneaded well, and then the mixture is filled into a container and molded.

Example 10 Emulsion Foundation (Cream Type) (Prescription) (Powder Part) Titanium Dioxide 10.3% by Weight Sericite 5.4 Kaolin 3.0 Yellow Iron Oxide 0.8 Bengala 0.3 Black Iron Oxide 0.2 (Oil phase) Decamethylcyclopentasiloxane 11.5 Liquid paraffin 4.5 Polyoxyethylene-modified dimethylpolysiloxane 4.0 (Aqueous phase) Purified water 50.0 1,3-Butylene glycol 4.5 Pre Ethanol extract 1.5 Sorbitan sesquioleate ester 3.0 Preservative proper amount Perfume proper amount (Production method) After the aqueous phase is heated and stirred, the powder portion thoroughly mixed and pulverized is added and treated with a homomixer. Further, the oil phase mixed by heating is added, and the mixture is treated with a homomixer. Then, a fragrance is added with stirring, and the mixture is cooled to room temperature.

[0036]

As described above, the external preparation for skin of the present invention has an excellent tyrosinase activity inhibitory action and collagen production promoting action, and is effective in preventing pigmentation, spots, freckles, liver spots, etc. after sunburn. Has excellent lightening and whitening effects, promotes collagen production, can maintain elastic, wrinkle-free and slack-free skin, prevents skin aging, and provides youthful skin condition Can be maintained.

Continuation of the front page (51) Int.Cl. ⁶ Identification code Internal reference number FI Technical display location A61K 35/78 A61K 35/78 T N B ADA ADAJ AED AEDC C12N 9/99 C12N 9/99 (72) Inventor Naomi Tanaka, 1050 Shinba-cho, Kohoku-ku, Yokohama-shi, Kanagawa Within Shiseido Daiichi Research Center, Inc. (72) Inventor, Eiichiro Yagi, 1050, Shinba-cho, Kohoku-ku, Yokohama-shi, Kanagawa, Shiseido Daiichi Research Center (72) Inventor Hirohiko Sakamoto 1050 Shinba-cho, Kohoku-ku, Yokohama-shi, Kanagawa Shiseido Daiichi Research Center Co., Ltd.

Claims (4)

[Claims] 1. An external preparation for skin, which comprises one or more selected from the following plant extracts. (1) Pule (scientific name: Alstonia scholaris) (2) Uret-uret (scientific name: Helicter
es ixora L.) 2. The external preparation for skin according to claim 1, which is a tyrosinase inhibitor. 3. The external preparation for skin according to claim 1, which is an anti-aging agent. 4. The external preparation for skin according to claim 3, which is a collagen production promoter.