JP3499971B2 - Hair restoration and hair restoration - Google Patents

Description

Description: BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a hair-growth / hair-growth material, and more particularly to a hair-growth / hair-growth that promotes the growth of hair follicle tissue and is excellent in promoting hair growth. About charges. [0002] Almost all alopecia such as male pattern baldness, alopecia areata, etc., the mechanism and details of its onset are unknown. Conventionally, natural medicine extracts, blood circulation enhancers, immunosuppressants, metabolic enhancers, vitamins, antiandrogens, and the like have been used empirically for the treatment. However, these drugs often have no effect depending on the symptoms and individuals, and their effects have not been satisfactory. [0003] Therefore, there has been a demand for the development of a hair-growing / hair-growing agent that promotes the fundamental growth of hair and has excellent hair-growth activity against many alopecia. [0004] The present inventors have screened various biological components and physiological function regulators widely in view of such circumstances, and surprisingly have a plasminogen activator inhibitory action. It has been found that the substance has a hair follicle tissue growth and hair elongation action, and is useful as a hair growth and hair restoration material having excellent hair growth activity regardless of the type of alopecia, and has completed the present invention. . That is, the present invention relates to Ala-Arg-Met-Ala-Pro-
An object of the present invention is to provide a hair restoration / hair restoration material containing a hexapeptide represented by Glu. [0006] The components having a plasminogen activator inhibitory activity used in the present invention are not particularly limited. For example, plasminogen activator inhibitor 1, plasminogen activator inhibitor 2, plasminogen activator・ Inhibitor 3, Protease Nexin 1, Benzamide,
6-aminocaproic acid, tranexamic acid, aprotinin, soybean-derived trypsin inhibitor, formula (1): X ¹ -Arg-Met-Y ¹ (1) wherein X ¹ -is H-, Ala-, Ser-Ala-, Val-S
er-Ala- or indicates Ile-Ser-Ala-, -Y ¹ is -H, -Ala, -Ala
An oligopeptide represented by -Pro, -Ala-Pro-Glu or -Ala-Pro-Thr), which is represented by the formula (2): X ² -Arg-Thr-Y ² (2) Wherein X ² -is H-, Gly-, Thr-Gly- or Met
-Thr-Gly-, -Y ² is -H, -Gly, -Gly-His or -Gly-H
an oligopeptide represented by is-Gly) and X ³ -Arg-Ser-Y ³ (3) wherein X ³ -is H-, Phe -, Thr-Phe-, Phe-T
indicates hr-Phe-, Ala-, Ile-Ala- or Leu-Ile-Ala-, -Y ³
Is -H, -Ala, -Ala-Arg, -Ala-Arg-Leu, -Ser, -Ser-Pro
Or -Ser-Pro-Pro). In the above formulas (1) to (3), X ¹ ,
When Y ¹ , X ² , Y ² , X ^3, and Y ³ represent H, it means that there is no substituent at the N-terminus and C-terminus of these formulas (1) to (3), and the peptide is a dipeptide. Among these components, the above formulas (1) to (1)
The oligopeptide represented by (3) is more preferred, and the oligopeptide represented by formula (1) is particularly preferred. In addition, these oligopeptides can be synthesized by a conventional method, for example, by an automatic peptide synthesizer. Among the above-mentioned components, plasminogen activator inhibitor 1 and plasminogen activator inhibitor 2 are described in JP-A-6-27.
No. 9316 discloses that it shows an excellent effect on abnormal keratinization, but does not disclose any effect of these components on hair elongation. The above-mentioned components having a plasminogen activator inhibitory action can be used alone or in combination of two or more. The amount of the components is not particularly limited. 0.00 in fee
It is preferably from 0.01 to 20% by weight, particularly preferably from 0.01 to 10% by weight. The above-mentioned component having a plasminogen activator inhibitory effect may be used alone without using other components in combination. However, in order to further enhance the hair growth effect, a blood circulation promoting agent, an antibacterial agent, It may be used in combination with other components such as a solubilizer, an antiseborrheic agent, a local irritant, an anti-inflammatory agent, a humectant, an antiandrogen, and a hair follicle activator. These other components do not act directly on hair elongation, but have a different mechanism from the components having a plasminogen activator inhibitory effect, so that the combined use exerts a stronger hair-growth effect. For example, blood circulation enhancers enhance nutrition and supply of metabolites from hair mother cells,
Antibacterial agents also indirectly promote hair growth by suppressing the action of bacteria on the scalp. Among these components, blood circulation promoters include acetylcholine, syrup extract, carrot extract, ginkgo extract, carpronium chloride, diphenhydramine hydrochloride, γ-oryzanol, circretin, cromakalim, cepharanthin, nicorandil, vitamin E, vitamin E nicotinate And the like, pinacidyl, minoxidil, phthalides, kina extract, shobu root extract, spruce extract, this drug extract, yuzu extract and the like. Among them, acetylcholine, assembly extract, carrot extract, ginkgo extract, vitamin E and its derivatives, cepharanthin, minoxidil, carpronium chloride, diphenhydramine hydrochloride, γ-oryzanol, circretin, cromakalim, cepharanthin, nicorandil, pinacidil, minoxidil, phthalides, kina extract , Shobu root extract, spruce extract,
This drug extract and yuzu extract are preferable, and particularly, assembly extract, carrot extract, ginkgo extract, vitamin E and its derivatives, cepharanthin, minoxidil, carpronium chloride, and phthalides are preferable. Examples of the antibacterial agent include isopropylmethylphenol, benzalkonium chloride, octopirox, photosensitive dye 101, photosensitive dye 201, chlorhexidine, salicylic acid, zinc pyrithione, potassium sorbate, biosol, hinokitiol, and phenol. In addition, as a local stimulant, camphor, l-menthol, nonylate vanillylamide, ginger tincture,
Dutch galaxy extract, cantaris tincture, salamander extract, peppermint oil, wasabi radish extract and the like.
Of these, octopirox, benzalkonium chloride,
Zinc pyrithione, salicylic acid and isopropylmethylphenol are preferred. Examples of the keratolytic agent include aspirin and the like. Antiseborrheic agents include sulfur, thioxolone, banside, polysorbates, lecithin, cashew extract and the like. Examples of the anti-inflammatory agent include azulene, guaiazulene, antihistamines (diphenhydramine and the like), hydrocortisone acetate, prednisolone, pentagon extract, chamomile extract, sagebrush extract, fennel extract, kyonin extract, gardenia extract, kumazasa extract, gentian extract, konjiana extract Free extract, hawthorn extract, birch extract, Yarrow extract,
Gentle oil extract, tonin extract, peach leaf extract, loquat leaf extract and the like. Examples of humectants include hypericum, soluble collagen, glycerin, chondroitin sulfate, tuberose polysaccharide, cordyceps, trisaccharide, urea, biohyaluronic acid, hyaluronic acid, calcium vitamin C phosphate, sodium pyrrolidone carboxylate, propylene Glycol, prolonged life extract,
Barley extract, orange extract, seaweed extract, cucumber extract, burdock extract, shiitake extract, syrup extract, duke extract, loquat extract, grape leaf extract, prune extract, loofah extract, Maikai extract,
Mini Sasanishiki, lily extract, apple extract and the like can be mentioned. Examples of the antiandrogen include ethinyl estradiol, chlormadinone acetate and the like. As the hair follicle activator, N-acetyl-L-
Methionine, disodium adenosine triphosphate, potassium aspartate, photosensitive dye 301, pentadecanoic acid glyceride, netacanal, ethyl pantothenate, panthenol, biotin, mononitroguaiacol sodium, yeast extract, pearl protein extract, daisy extract, chik Ginseng, garlic components, placenta extract, royal jelly extract and the like. The above-mentioned other components are preferably used alone or as a mixture of two or more, and are preferably used after being dissolved in water or a solvent such as water-lower alcohol. The above-mentioned other components are added to the hair-growing / hair-growing agent of the present invention in an amount of 0.1% from the viewpoint of synergistic effect with a component having a plasminogen activator inhibitory effect and irritation to the scalp.
It is preferable to add 001 to 5% by weight, particularly 0.01 to 3% by weight. The hair-growing / hair-growing agent of the present invention is used as an external preparation, and its dosage form is mainly liquid, and is typically a lotion, but it can also be a cream or gel. It is particularly preferable that the liquid preparation further contain carbon dioxide gas. Carbon dioxide gas is the pH of the solution in which it is dissolved.
It is known that when is acidic, it exists as a CO ₂ molecule and exhibits a vasodilator effect. Therefore, the liquidity of the hair growth and fostering composition of the present invention containing carbon dioxide is pH 7 or less, especially pH
It is preferable to adjust to 4.5 to 6.5. In addition, hair growth
The pH of the hair restorer is such that carbon dioxide gas is injected into the hair restorer and the acidity further increases when the carbon dioxide gas dissolves into the hair restorer / hair restorer. The pH may be adjusted so that the final pH falls within the above range. As the pH adjuster, for example, organic acids such as citric acid, tartaric acid and lactic acid or salts thereof, or phosphoric acid or salts thereof are suitably used. In order to incorporate carbon dioxide into the hair growth and fostering material of the present invention, a method other than putting carbon dioxide into a pressure-resistant container and filling the container with high-pressure carbon dioxide, sodium bicarbonate or the like in the pressure-resistant container A method of adding a component that generates carbon dioxide gas containing carbonate and adding a pH adjuster to the mixture to generate carbon dioxide gas and sealing immediately, or a method of sealing by placing dry ice pellets in a container, etc. Although it is adopted, a method of filling high-pressure carbon dioxide gas is particularly preferable. In this case, a part of the carbon dioxide gas is dissolved and mixed in the hair growth and fostering material of the present invention, and a part thereof is present as a gas in the container. In the present invention, it is important that the carbon dioxide gas is dissolved and compounded in the hair growth and hair growth material, and the compounding amount is preferably a carbon dioxide gas concentration of 60 ppm or more. Cannot be obtained. The amount of carbon dioxide gas can be adjusted by the amount of carbon dioxide gas injected (press-fitted). In general, the pressure in the vessel is 35 ° C. and 1.2 to 8 kg / cm ^2.
(Gauge pressure). In addition to the above-mentioned components, the hair-growing / hair-growing composition of the present invention may contain, if necessary, oily bases, gelling agents, and various kinds of oils used in ordinary cosmetics, as long as the effects of the present invention are not impaired. Emulsifiers, fragrances, antioxidants such as parahydroxybenzoic acid esters, and coloring agents such as dyes can be added and blended. Specifically, distilled water, lower alcohols such as ethanol, higher alcohols such as cetanol, and propylene Examples include polyhydric alcohols such as glycol, vaseline, silicone, and surfactant. The hair-growing / hair-growing agent of the present invention can be produced by subjecting the above-mentioned essential components and optional components to operations such as mixing according to a conventional method. EFFECTS OF THE INVENTION The hair-growing / hair-growing agent of the present invention promotes the growth of hair follicle tissue and is excellent in promoting hair growth directly, so it is excellent against many alopecia irrespective of symptoms and individual differences. Has hair growth activity. EXAMPLES The present invention will be described in more detail with reference to the following Examples, but it should not be construed that the present invention is limited thereto. Example 1 <Effect on Hair Shaft Elongation> A hair follicle tissue was surgically removed from a one-week-old Wistar rat and cultured on a stainless steel mesh in a tissue culture dish for 4 days. The culture was performed using RPMI 1640 as a medium at 37 ° C.
The test was performed under the conditions of 90% O ₂ and 5% CO ₂ . The test sample was added to the medium at a concentration of 1 μM to 100 μM. After the culture, hair elongation was observed.
It was represented by a relative value when it was set to 00%. As a result, Table 1
As shown in the figure, a component having a plasminogen activator inhibitory action had a clear hair elongation promoting effect. [Table 1] Example 2 <Effects on Tissue Culture Hair Follicle> Tissue culture hair follicles and skin fibroblasts were collected from Wistar rats aged 4 days according to a conventional method, and mixed and cultured in a collagen gel.
Using M199 as a medium, 37 ° C., 90% O ₂ , 5%
The test was performed under the condition of CO ₂ . Hexapeptide (Ala-Arg-Met-A
la-Pro-Glu) was added to the medium at a concentration of 0.03-1 μM. Sixteen hours later, thymidine uptake in the tissue culture hair follicles was measured and expressed as a relative value when the control group was taken as 100%. As a result, as shown in Table 2, a component having a plasminogen activator inhibitory effect was found to have an effect of promoting the growth of tissue culture hair follicles, which is important for hair construction. [Table 2] Example 3 Hair Restoration and Hair Restorative (Table 3) (% by weight) A Polyoxyethylene hydrogenated castor oil 0.8 Ethanol 30.0 B Hexapeptide (Ala-Arg-Met-Ala-Pro-Glu) 1 0.0 Sodium dodecyl sulfate 0.1 Dodecylmethylamine oxide 0.2 Isopropyl alcohol 15.0 Benzyl alcohol 15.0 Fragrance 0.1 Purified water Balance Dissolve components belonging to A and dissolve components belonging to B separately Then, B was added to A, and the mixture was uniformly stirred and mixed to obtain a hair restoration / hair restoration material. Example 4 Hair restorer / hair restorer (Table 4) (% by weight) A Hexapeptide (Ala-Arg-Met-Ala-Pro-Glu) 1.0 Cetanol 1.2 Propylene glycol 4.0 Ethanol 50. 0 pH adjuster (lactic acid) Appropriate amount Fragrance 0.1 Purified water Balance B Carbon dioxide 2.0 The components belonging to A were uniformly mixed and placed in a container, and B was filled into the container by a conventional method. Example 5 Hair Restoration / Hair Restorative (Table 5) (% by weight) A Hexapeptide (Ala-Arg-Met-Ala-Pro-Glu) 1.0 Cetanol 1.2 Propylene glycol 4.0 Ethanol 40. 0 Perfume 0.1 Purified water Balance B Propellant (dimethyl ether; DME) 10.0 The components belonging to A were uniformly mixed and placed in a container, and B was filled into the container by a conventional method.

──────────────────────────────────────────────────続 き Continuation of the front page (72) Inventor Mitsuyuki Hotta 2606 Akabane, Kaiga-cho, Haga-gun, Tochigi Prefecture Kao Co., Ltd. Research Institute (56) References (JP, A) JP-A-5-331024 (JP, A) JP-A-7-126173 (JP, A) JP-A-6-9425 (JP, A) JP-A-5-328997 (JP, A) Published Japanese Patent Application No. Hei 7-51097 (JP, A) Table of International Patent Application No. Hei 11-504016 (JP, A) WO 95/011987 (WO, A1) (58) Fields investigated (Int. Cl. ⁷ , DB name) A61K 7 / 00-7/50 CA (STN)

Claims (1)

(57) [Claims] [Claim 1] A hair restorer / hair restorer containing a hexapeptide represented by Ala-Arg-Met-Ala-Pro-Glu.