JPH0987135A - Dermal preparation for external use - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a dermal preparation for external use, having excellent inhibiting actions on the tyrosinase activities and promoting actions on the production of collagen, effective in lightening the color and beautifying and whitening of pigmentation, dermal stains, ephelides, chloasma, etc., after sunburn and capable of preventing the skin from aging. SOLUTION: This dermal preparation for external use comprises an extract of a plant belonging to the genus Elephamtopus of the family Compositae [e.g. Tapak limam (botanical name: Elephamtopus scaber L.)] as an active ingredient in an amount of 0.0005-20wt.%, preferably 0.001-10wt. expressed in terms of a dried substance therein. The Tapak limam is the plant growing in especially a dry grassland, a pasture, etc., of Indonesia and the extract is obtained by immersing the whole herb together with an organic solvent such as ethanol therein or refluxing the mixture under heating, then filtering and concentrating the resultant filtrate. Usually used ingredients can further suitably be blended therewith to prepare an ointment, a cream, a milky lotion, a lotion, a pack, a bathing agent, etc. Thereby, the elastic skin without any wrinkles or slacks can be retained to maintain the state of the fresh 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]

2. Description of the Related Art Although there are some unclear points about the mechanism of the occurrence of skin spots and the like, melanin pigments are generally formed due to hormonal abnormalities and stimulation of ultraviolet rays from sunlight. It is believed to be abnormally deposited within. This melanin pigment, which causes skin coloring, is produced in melanin-producing granules (melanosomes) in melanocytes (melanocytes) between the epidermis and dermis,
The generated melanin diffuses into adjacent cells by the osmotic effect. 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.

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, by acting on the fibroblasts in the skin and promoting the biosynthesis of collagen, which is one of the important components of the dermis, it is possible to prevent the aging of the skin and promote collagen production, which is safe in terms of safety. A drug was desired.

[0005]

Compounds that suppress the action of tyrosinase, except for hydroquinone, exhibit extremely slow effects, and therefore 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, as a component having an action of acting on fibroblasts in the skin to biosynthesize collagen which is one of the important components of the dermis, rice previously found by the applicants was proteolytic enzyme. An enzyme-decomposed product obtained by treating an alkaline extract of low-allergenic rice obtained by treating with an enzyme with an enzyme is known (Japanese Patent Application No. 7-243463,
Japanese Patent Application No. 8-97654). Further, a further substance having an excellent ability to promote collagen production has been desired.

[0007]

Therefore, as a solution to these problems, the present inventors investigated the tyrosinase activity-inhibiting ability and collagen production-promoting ability of a wide variety of substances. As a result, the elephant path of the family Compositae ( It was found that an extract of the genus Elephamtopus) has excellent tyrosinase activity inhibitory action and collagen production promoting action, and has completed the present invention. There have been no reports of tyrosinase activity-inhibiting activity and collagen production-promoting activity of extracts from plants of the genus Elephamtopus (Compositae), let alone application to whitening agents and anti-aging agents, or to skin external preparations. No application is known at all. The present inventors have completed the present invention based on the above findings.

[0008] That is, the present invention is a skin external preparation characterized by containing an extract of a plant of the genus Elephamtopus belonging to the family Compositae. The external preparation for skin of the present invention is preferably a tyrosinase inhibitor or an anti-aging agent, and is preferably a collagen production promoter among the anti-aging agents.

The structure of the present invention will be described in detail below. Examples of the plant of the genus Elephantpath (Elephamtopus) used in the present invention include Tapak limam (scientific name: Elephamtopus scaber).
L.) is preferred. Tapak Liman is a plant that grows especially on Indonesian dry grasslands and pastures. The extract of the plant of the genus Elephant path (Elephamtopus) used in the present invention is a leaf of the above plant,
Stems, flowers, bark, seeds or fruits, whole plants, etc. are immersed or heated under reflux with an extraction solvent, filtered, and concentrated. The extraction solvent used in the present invention is not particularly limited as long as it is a solvent usually used for extraction. In particular, an organic solvent such as alcohols such as methanol and ethanol, aqueous alcohols, acetone, and ethyl acetate is used alone or in combination. Can be.

The amount of the extract of the plant of the genus Elephamtopus belonging to the family Compositae in the present invention is 0.0005 to 20% as a dry product in the total amount of the external preparation.
It is 0% by weight, preferably 0.001 to 10.0% by weight. 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.

[0011] In addition to the above essential components, the skin external preparation of the present invention contains components usually used in skin external preparations such as cosmetics and pharmaceuticals, for example, other whitening agents, humectants, antioxidants, and oily components. , UV absorbers, surfactants, thickeners,
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 fruits of fire thorns, various crude drugs, tocopherol acetate,
Drugs such as glycyrrhizic acid and its derivatives or salts thereof, vitamin C, magnesium ascorbate phosphate,
Other whitening agents such as ascorbic acid glucoside, arbutin, kojic acid, glucose, fructose, mannose,
Sugars such as sucrose and trehalose can also be appropriately blended.

The external preparation for skin of the present invention may be any ointment, cream, milky lotion, lotion, pack, bath agent or the like which is conventionally used for external preparations for skin, and the dosage form is not particularly limited.

[0014]

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, the test method and the results concerning the tyrosinase activity inhibitory effect and collagen production promoting effect of the plant extract of the present invention will be described.

1. Sample preparation (1) Tapak limam extract Tapa liman grass part 5
0 g was immersed in ethanol at room temperature for 1 week and the extract was concentrated to obtain 1.5 g of an ethanol extract. This extract was dissolved in DMSO at 1%, the concentration was adjusted by diluting this solution, and the following experiment was performed using this.

2. Test method and its result Tyrosinase activity inhibitory effect (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 Before the 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 the table, "toxic" means that cytotoxicity was observed, and "-" means that no significant difference was observed within a risk rate of 5% as compared with the control.

[0018]

[Table 1] ───────────────────────────── Test tyrosinase activity (%) ─────────── ────────────── Concentration (wt%) 10 ^-5 10 ^-4 10 ^-3 10 ^-2 ─────────────────── ────────── Tapak Liman Extract 86 38 Toxic Toxicity Toxicology oyster extract − − − 55 ──────────────────────── ─────

Collagen production accelerating effect (1) Cell culture method and measurement of collagen production accelerating action Human skin fibroblasts were seeded in a 96-well petri dish, 20,000, 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. Regarding the Tapak Liman extract, cytotoxicity was observed at 10 ^-3 % by weight, but no toxicity was observed at 10 ^-4 % by weight. Therefore, type I procollagen C-terminal peptide (Pr produced by cultured human skin fibroblasts)
ocollagen type I carboxyterminal propeptide: PIP)
Was measured by the ELISA method. The amount of PIP per DNA of the sample (control) to which the plant extract was not added was 1
The amount of PIP of the plant extract-added sample having a concentration of 10 ⁻⁴ % by weight was measured as 00, and was defined as the collagen production promoting rate (%). The results are shown in Table 2. Further, as a reference example, the same test as above is performed on a solvent extract of Hishimi, which is already known to have a collagen production promoting action,
The rate of promotion of collagen production was measured at a concentration of 10 ⁻³ % by weight. The results are also shown in Table 2.

[0020]

[Table 2] ──────────────────────────────── Test Collagen production promoting effect (%) ────── ────────────────────────── Tapak Liman extract (10 ^-4 % concentration) 168 Hishimi extract (10 ^-3 % concentration) 124 ────────────────────────────────

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 Tapak / Remanmethanol extract 0.01 Caustic potassium 0.2 Sodium bisulfite 0.01 Preservative proper amount Perfume proper amount Ion-exchanged water Residual (manufacturing method) Dissolve propylene glycol, Tapak Limanmethanol extract and caustic potash in ion-exchanged water, heat and keep at 70 ° C ( Water phase). The other ingredients are mixed, heated and melted and maintained at 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. After that, homogenize with a homomixer,
Cool to 30 ° C with good stirring.

Example 2 Cream (prescription) 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 Tapak Liman ethanol extract 0.05 Sodium hydrogen sulfite 0.03 Ethylparaben 0.3 Perfume proper amount Ion-exchanged water Residual (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 Tapak / Reman acetone extract 0.05 Tapak / Reman ethanol extract 0.05 Sodium hydrogen sulfite 0.03 Ethyl paraben 0.3 Perfume proper amount Ion-exchanged water Residual (production method) ion Soap powder and borax are added to exchanged water, and the mixture is 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% by weight 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) Tapak / Lyman acetic acid ethyl ester extract 0.01 Sodium bisulfite 0.01 Ethylparaben 0.3 Perfume proper amount Ion Exchanged water Residue (production method) A 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 Tapak / Remanacetone extract 10.0 Sodium hydrogen sulfite 0.01 Ethylparaben 0.3 Fragrance suitable amount Ion-exchanged water Residual (production method) Propylene glycol is added to ion-exchanged water In addition,
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 wt% 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 Tapak limant 50% ethanol aqueous solution extract 7.0 2-Hydroxy-4-methoxybenzophenone sodium sulfonate 0.05 Ethylenediaminetetraacetate-3 sodium-2 Water 0.05 Methylparaben 0.2 Perfume Appropriate amount Ion-exchanged water Residual (production method) Carbopol 940 is uniformly dissolved in ion-exchanged water, while tapak reman 50% in 95% ethanol
An aqueous ethanol solution extract and polyoxyethylene (50 mol) oleyl alcohol ether are dissolved and added to the aqueous phase. Next, after adding other ingredients, caustic soda,
Thicken by neutralizing with L-arginine.

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 Tapak Remanmethanol 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 wt% Polyoxyethylene (60 mol) hydrogenated castor oil 5.0 (Phase B) Tapak Liman methanol extract 0.01 Olive oil 5 0.0 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 Residue (Manufacturing method) Phase A, phase B, and phase C 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 octoate 2.0 Tapak / Reman ethanol extract 1.0 Preservatives appropriate amount Perfume appropriate amount (manufacturing method) Talc-black iron oxide powder component is sufficient with a blender After mixing, an oily component of squalane to isocetyl octoate, an extract of tapak and reman ethanol, an antiseptic and a fragrance are added and kneaded well, then filled into a container and molded.

Example 10 Emulsion type foundation (cream type) (Formulation) (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 (water phase) purified water 50.0 1,3-butylene glycol 4.5 tapak Liman ethanol extract 1.5 sorbitan sesquioleate 3.0 preservative proper amount perfume proper amount (manufacturing method) The aqueous phase is heated and stirred, and then the powder portion thoroughly mixed and pulverized is added to perform homomixer treatment. 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.

[0032]

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 front page (51) Int.Cl. ⁶ Identification number Internal reference number FI Technical display location A61K 35/78 ADS A61K 35/78 ADS AED AEDT AGZ AGZT C12N 9/99 C12N 9/99 (72) Inventor Yoshihiro Yokokawa 1050 Shinba-cho, Kohoku-ku, Yokohama-shi, Kanagawa Inside Shiseido Daiichi Research Center (72) Inventor Naomi Tanaka 1050, Shinba-cho, Kohoku-ku, Yokohama-shi, Kanagawa Shiseido Daiichi Research Center 72) Inventor Eiichiro Yagi, 1050 Shinba-cho, Kohoku-ku, Yokohama-shi, Kanagawa Inside Shiseido Daiichi Research Center, Inc. In the center

Claims (5)

[Claims] 1. An external preparation for skin, comprising an extract of a plant of the genus Elephamtopus belonging to the family Compositae. 2. A plant of the genus Elephamtopus of the family Compositae is Tapak Liman.
Limam, scientific name: Elephamtopus scaber L.), The external preparation for skin according to claim 1. 3. The external preparation for skin according to claim 1, which is a tyrosinase inhibitor. 4. The external preparation for skin according to claim 1, which is an anti-aging agent. 5. The external preparation for skin according to claim 4, which is a collagen production promoter.