JP2008280325A - External preparation for skin, hair restoration or hair growth agent, and external preparation for lip - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide an external preparation for the skin for improving wrinkle and sagging, external preparation for moisturizing, hair restoration or growth agent, external preparation for promoting the healing of wounds and external preparation for the lips which contain a natural effective component. <P>SOLUTION: The external preparation for the skin for improving wrinkle and sagging, external preparation for moisturizing, hair restoration or growth agent, external preparation for promoting the healing of wounds and external preparation for the lips contain raspberry ketone as an effective component. <P>COPYRIGHT: (C)2009,JPO&INPIT

Description

  The present invention relates to a skin external preparation, and more particularly to a skin external preparation for improving wrinkles or sagging, moisturizing, and promoting wound healing. The present invention also relates to a hair growth or hair growth agent. Furthermore, the present invention relates to a lip external preparation such as lipstick, lip balm and lip gloss.

In modern times, wrinkles and sagging caused by aging, ultraviolet rays, and drying of the environment due to loss of skin tension and elasticity, and dry and rough lips are particularly troublesome for women. In addition, due to recent natural orientation, it is required to use natural ingredients as active ingredients in cosmetics.
Here, Patent Document 1 describes that when a skin lotion containing 0.1 to 3% by weight of raspberry ketone was applied to a woman's skin every day, the skin became moistened and the skin became bright. In addition, as an action mechanism exhibiting these effects, it is described that photoaging is suppressed by suppressing generation of nitric oxide, lipid peroxide, and active oxygen.
Patent Document 2 describes that the raspberry ketone extract increased the granule weight increasing effect, the collagen synthesizing ability improving effect, and the tissue repair ability improving effect of the paffia extract.
Patent Document 3 describes that raspberry ketone nicotinate has an effect of improving skin firmness, gloss, flexibility, and brightness.
In addition, the number of men and women who suffer from thinning hair and hair loss is increasing in modern times, but it has been pointed out that these factors are greatly influenced by stress in addition to factors such as genetic predisposition and aging.
For this reason, a large number of pharmaceuticals and medicinal cosmetics intended for hair growth are developed and widely used. Minoxidil, various plant extracts, and the like are used as active ingredients of such pharmaceuticals and medicinal cosmetics (Patent Documents 4 and 5). However, the effect of conventional plant-derived hair restorers is not sufficient in practice. Note that Non-Patent Document 1 describes that when hair regeneration was attempted using a coating containing raspberry ketone, it was suggested that the hair-growth action was ineffective.
JP 2000-290177 A (paragraphs 0033, 0036, 0002, 00029) JP 2005-255527 A (paragraph 0030) JP 2005-41780 A Japanese Patent Laid-Open No. 5-4908 Japanese Patent Laid-Open No. 11-193219 Medicine and biology, 2003, Vol.146, No.4, p71-74

  The present invention provides a skin external preparation for improving wrinkles or sagging, a skin external preparation for moisturizing, a skin external preparation for promoting wound healing, a hair growth or hair growth agent, and a lip external preparation containing natural active ingredients. Is an issue.

The present inventor repeated researches to solve the above-described problems, and obtained the following knowledge.
(i) By applying raspberry ketone to the skin, the concentration of insulin-like growth factor-1 (hereinafter sometimes referred to as “IGF-1”) in the skin tissue is increased. Raspberry ketone improves IGF-1 concentration in the skin when applied to the skin.
(ii) Wrinkle and sagging are improved by applying raspberry ketone to the skin, and drying and that are improved by applying raspberry ketone to the lips.
(iii) When raspberry ketone is applied to the scalp, hair growth or hair growth occurs by promoting the secretion of IGF-1 in the scalp. Moreover, it is thought that raspberry ketone accelerates | stimulates healing of a wound through the IGF-1 density | concentration improvement in the said part by apply | coating to the wound part of skin.

The present invention has been completed based on the above findings, and provides the following external preparations and the like.
Item 1. An agent for hair growth or hair growth containing raspberry ketone.
Item 2. Item 2. The agent according to Item 1, which promotes hair growth or hair growth by promoting the secretion of insulin-like growth factor-1.
Item 3. Item 3. The agent according to Item 1 or 2, comprising 0.005 to 0.05% by weight of the raspberry ketone.

  The skin external preparation, hair growth or hair growth preparation, and lip external preparation for improving wrinkles or sagging, moisturizing, and promoting wound healing of the present invention each contain raspberry ketone as an active ingredient.

Raspberry ketone increases the IGF-1 concentration in the skin, thereby improving wrinkles and sagging, improving dryness or roughness, promoting wound healing, and promoting hair growth or hair growth. As for dryness or roughness, it particularly improves dryness or roughness of the lips.
IGF-1 is a peptide hormone with a molecular weight of approximately 7,500 that has a structure and action very similar to insulin. IGF-1 is known to actively maintain cells in a healthy state and prevent the progression of aging, such as promoting cell differentiation and helping cell proliferation. For example, in the skin, IGF-1 activates fibroblasts and promotes their differentiation.

  Fibroblasts promote the production of interstitial materials such as collagen, elastin and hyaluronic acid. Collagen is a major protein that constitutes connective tissues such as dermis, ligaments, tendons, bones, and cartilage, and skin collagen is involved in skin shape formation such as skin texture and elasticity. Elastin is a fibrous protein that works extracellularly like collagen, and has a property of stretching and shrinking like rubber, and has a function of maintaining the elasticity and elasticity of the skin. Hyaluronic acid is a type of glycosaminoglucan that is distributed in large amounts in the connective tissue of mammals, moisturizes the skin, and plays a role of cushion. For this reason, an increase in IGF-1 in the skin leads to an improvement in skin elasticity, skin tension, and skin moisture.

  IGF-1 has a blood flow increasing action and a hair follicle growth promoting action in addition to the TNF-α production inhibitory action involved in the expansion of the inflammatory reaction, and the transition from the resting stage to the growing stage in the hair cycle. It is thought that it plays an important role in extending the growth period. The above-mentioned action of IGF-1 is described in the following documents (a) to (d).

(a) Vignery A, McCarthy TL, The neuropeptide calcitonin gene-related peptide stimulates insulin-like growth factor 1 production by primary fetal rat osteoblasts, Bone, 1996, Vol 18, No 4, 331-335
(b) Philpott MP, Sanders DA, Kealey T, Effects of insulin and insulin-like growth factors on cultured human hair follicles: IGF-1 at physiologic concentrations is an important regulator of hair follicle growth in vitro, J Invest Dermatol, 1994, Vol 102, No 6, 857-861
(c) Conn KJ, Rich CB, Jensen DE, Fontanilla MR, Bashir MM, Rosenbloom J, Foster JA.Insulin-like growth factor-I regulates transcription of the elastin gene through a putative retinoblastoma control element.A role for Sp3 acting as a repressor of elastin gene transcription. L. Biol. Chem. 1996 217 (46) 28853-60
(d) Catherine Braham, Daniela Betea, Claudine Pierard-Franchimont, Albert Beckers, Gerald E. Pierard.Skin Tensile Properties in Patients Treated for Acromegaly.Dermatology 2002 20 (4): 325-329
Since raspberry ketone is a component contained in natural materials such as raspberry, the external preparation of the present invention has a mild action and no side effects. That is, it is excellent in safety.

The present invention will be described in detail below.
(I) Skin external preparation for improving wrinkles or sagging The skin external preparation for improving wrinkles or sagging according to the present invention is an external preparation containing raspberry ketone as an active ingredient. This external preparation improves wrinkles or sagging through the action of raspberry ketone to increase the concentration of IGF-1 in the skin. This external preparation is also effective in preventing wrinkles or sagging.
Improving wrinkles or sagging includes reducing the degree of wrinkles or sagging, reducing the number of wrinkles or sagging, and eliminating wrinkles or sagging at all. Further, prevention of wrinkles or sagging includes avoiding or suppressing the occurrence of wrinkles or sagging and suppressing the progress of the degree of wrinkles or sagging. The improvement and prevention effects are particularly pronounced on the skin of the face and lips.

ラズベリーケトンは、ラズベリー由来のものであってもよく、合成品であってもよい。安全でかつ入手が容易である点で、ラズベリー由来のものが好ましい。ラズベリー由来のものを使用する場合は、ラズベリーの果実や葉の粉砕物（粉末を含む）を用いてもよく、ラズベリーの果実や葉の抽出物を用いてもよく、このラズベリー抽出物を各種クロマトグラフィー等を用いて精製したものを用いてもよい。ラズベリー抽出物は、例えば、ラズベリーの果実や葉の破砕物に５〜２０倍量の極性有機溶媒（例えば、水、メタノール、エタノール、1,3-ブチレンアルコール、アセトンなど）を添加して、室温で攪拌抽出し、不溶性固形分を除去することにより得られる。抽出液又は精製液は、そのまま用いてもよく、又は濃縮して用いてもよく、乾固物を用いてもよい。また、ラズベリーケトンは、（株）井上香料製造所、豊玉香料（株）等から市販されている。 Raspberry ketone Raspberry ketone is a compound represented by the following formula (1). In the present invention, the raspberry ketone may be a pharmaceutically acceptable salt. A raspberry ketone derivative may also be used. The type of the derivative is not particularly limited as long as the effect of the present invention is exhibited. For example, raspberry ketone nicotinate, raspberry ketone-D-glucoside (α and β form), raspberry ketone-D-galactoside (α and β form), raspberry ketone-D. Examples include pharmaceutically acceptable esters and glycosides such as -xyloside (α and β forms) and raspberry ketone-D-maltoside (α and β forms). As an active ingredient of a skin external preparation for improving wrinkles or sagging, a skin external preparation for moisturizing, a lip external preparation, and an external preparation for promoting wound healing, it is preferable to use raspberry ketone.

The raspberry ketone may be derived from raspberry or may be a synthetic product. Raspberry-derived ones are preferable because they are safe and easily available. When using a raspberry-derived product, a crushed product (including powder) of raspberry fruits and leaves may be used, or an extract of raspberry fruits and leaves may be used. What refine | purified using the graph etc. may be used. The raspberry extract is prepared by adding 5 to 20 times the amount of polar organic solvent (for example, water, methanol, ethanol, 1,3-butylene alcohol, acetone, etc.) to a crushed fruit or leaf of raspberry at room temperature. By stirring and extraction to remove insoluble solids. The extract or purified solution may be used as it is, or may be used after being concentrated, or a dried product may be used. Raspberry ketone is commercially available from Inoue Fragrance Co., Ltd., Toyoda Fragrance Co., Ltd. and the like.

  The content of raspberry ketone in the skin external preparation for improving wrinkles or sagging of the present invention is preferably about 0.005 to 0.05% by weight, more preferably about 0.0075 to 0.0125% by weight. Within the above range, the wrinkle or sagging of the skin is sufficiently improved by the IGF-1 concentration enhancing action, and the wrinkle or sagging improving action is sufficiently maintained for a long time. Further, when the content of raspberry ketone is about 0.0075 to 0.0125% by weight, the IGF-1 concentration in the skin is maximized, and a more excellent skin wrinkle or sagging improvement effect is exhibited.

(II) Skin external preparation for moisturizing The skin external preparation for moisturizing of the present invention is an external preparation containing raspberry ketone as an active ingredient. This external preparation increases the moisture or oil content of the skin through the action of increasing the concentration of IGF-1 in the skin of raspberry ketone, thereby improving the roughness caused by drying or drying of the skin. The effect is particularly remarkable on the skin of the face and lips. On the lips, not only will dryness and roughness be improved and it will return to a flat state, but it will also appear glossy and shiny. Moreover, the skin external preparation for moisturizing of this invention is effective also in prevention of the dryness of the skin and the roughness by drying. Improvements in drying and roughening include reducing the degree of drying and roughening and eliminating any dryness or roughening. Further, prevention of drying and roughening includes avoiding or suppressing the occurrence of drying and roughening and suppressing the progress of the degree of drying or roughening. The improvement and prevention effects are particularly pronounced on the skin of the face and lips.

  The content of raspberry ketone in the moisturizing skin external preparation of the present invention is preferably about 0.005 to 0.05% by weight, more preferably about 0.0075 to 0.0125% by weight. If it is the said range, the dryness or roughness of skin will fully be improved by the effect | action which raises IGF-1 density | concentration, and sufficient dryness and roughening effect of skin will be maintained over a long time. In addition, when the content of raspberry ketone is about 0.0075 to 0.0125% by weight, the IGF-1 concentration in the skin is maximized, and more excellent effects of improving skin dryness and roughness are exhibited.

(III) Hair Growth or Hair Growth Agent The hair growth or hair growth agent of the present invention is an agent containing raspberry ketone as an active ingredient. This agent promotes hair growth, grows and / or nourishes in the scalp through the action of raspberry ketone to increase the IGF-1 concentration in the skin. That is, in the present invention, hair growth includes hair nourishment. The agent for hair growth or hair growth of the present invention is also effective in preventing hair damage such as thinning and hair loss. Prevention of hair damage such as thinning and hair loss includes avoiding or suppressing the occurrence of hair damage and suppressing the progress of the degree of hair damage. That is, suppression of hair loss is also included in hair growth or hair growth.
It is not known at all that raspberry ketone or a derivative thereof has a hair growth effect or a hair growth effect. Rather, it is said that there is no hair growth effect as in Non-Patent Document 1.

  The content of raspberry ketone in the hair growth or hair growth preparation of the present invention is preferably about 0.005 to 0.05% by weight, more preferably about 0.0075 to 0.0125% by weight. If it is the said range, there exists sufficient hair growth or a hair growth effect by an IGF-1 density | concentration improvement effect, and sufficient hair growth or hair growth action is maintained over a long time. Further, when the content of raspberry ketone is about 0.0075 to 0.0125% by weight, the IGF-1 concentration in the skin is maximized, and a more excellent hair growth or hair growth effect is exhibited.

(IV) Skin external preparation for promoting wound healing The skin external preparation for promoting wound healing of the present invention is an external preparation containing raspberry ketone as an active ingredient. This external preparation heals skin wounds or injuries through the action of increasing the concentration of IGF-1 in the skin of raspberry ketone. In the present invention, healing includes improvement in addition to complete recovery.
The content of raspberry ketone in the external preparation for skin healing promotion of the present invention is preferably about 0.005 to 0.05% by weight, and more preferably about 0.0075 to 0.0125% by weight. If it is the said range, there exists sufficient wound-healing promotion effect by IGF-1 density | concentration improvement effect, and sufficient wound-healing promotion effect is maintained over a long time. Further, when the content of raspberry ketone is about 0.0075 to 0.0125% by weight, the IGF-1 concentration in the skin is maximized, and a more excellent wound healing promoting effect is exhibited.

(V) Dosage Form / Manufacturing Method In this item, the above-described skin external preparation for improving wrinkles or sagging, skin external preparation for moisturizing, hair growth or hair growth agent, and skin external preparation for promoting wound healing according to the present invention described above are used. The dosage form and manufacturing method will be described.
The dosage form of each external preparation of this invention is not specifically limited, The form employ | adopted as cosmetics, a pharmaceutical, or a quasi-drug can be employ | adopted without a restriction | limiting. Examples of the dosage form that can be used include pharmaceuticals or quasi-drugs such as liquids, suspensions, emulsions, creams, ointments, gels, liniments, lotions, and poultices. Also, for example, lipstick, lip balm, lip gloss, lotion, cosmetic emulsion, cosmetic cream, cosmetic gel, cosmetic lotion, pack, foundation, facial cleanser, body soap, hand cream, shampoo, rinse, hair conditioner And cosmetics such as skin care products and makeup products.
The skin external preparation for improving wrinkles or sagging of the present invention is preferably a cosmetic. The external preparation for moisturizing skin is preferably a cosmetic. The external preparation for skin healing promotion is preferably a pharmaceutical product.

Moreover, as a dosage form of the hair growth or hair growth agent of this invention, the form employ | adopted as cosmetics, a pharmaceutical, or a quasi-drug can be employ | adopted without a restriction | limiting.
In the case of a pharmaceutical product or quasi-drug, the dosage form may be either an oral preparation or a parenteral preparation, but a parenteral preparation, particularly an external preparation is preferred. Examples of the dosage form of the external preparation include aerosols, solutions, suspensions, emulsions, creams, lotions, ointments, gels, liniments, and poultices. Of these, aerosols, liquids, suspensions, emulsions, creams, and lotions are preferred.
Examples of cosmetics include skin lotions, cosmetic emulsions, cosmetic creams, cosmetic gels, cosmetic lotions, pack agents, shampoos, rinses, hair styling agents, and the like. When it is liquid, a spray is preferred.
The agent of the present invention may be prepared by adding, for example, a base component or an additive, which will be described later, to raspberry ketone according to the above dosage form, and mixing these components. In that case, it can be produced according to a known method, for example, the method described in the 15th revised Japanese Pharmacopoeia General Rules or the like, or the like.

  When the agent of the present invention is a liquid agent, for example, a solvent (for example, normal water, purified water, physiological saline, isopropanol, glycerin, ethanol, propylene glycol, Macrogol 400, etc .; hereinafter the same applies to the solvent). Etc. can be added and mixed and dissolved to produce a liquid preparation.

  When the agent of the present invention is a suspending agent, for example, a suspending agent or thickener (for example, gum arabic, carmellose, carmellose sodium, carmellose calcium, hydroxypropyl cellulose, hydroxypropyl methylcellulose, popidone, methylcellulose) , Aluminum monostearate, etc .; hereinafter the same in suspending agents or thickeners) and purified water or fatty oils (for example, synthetic oils such as medium-chain fatty acid triglycerides, hard fats, olive oil, soybean oil, rapeseed Oil, peanut oil, safflower oil, nutca oil, sesame oil, camellia oil, corn oil, menziz oil, coconut oil, squalane, etc., or hardened oils thereof; Can be stirred and homogenized to produce a suspension.

  When the agent of the present invention is an emulsion, for example, an emulsifier (for example, polyoxyl 40 stearate, sorbitan sesquioleate, polysorbate 80, sodium lauryl sulfate, lauromacrogol, gum arabic, cholesterol, stearic acid, glyceryl monostearate is added to raspberry ketone. , Popidone, etc .; hereinafter the same for emulsifiers) and purified water are added and stirred with a homomixer or the like to homogenize to produce an emulsion.

  When the agent of the present invention is a cream, raspberry ketone, oily components (eg, liquid paraffin, white petrolatum, etc.), higher alcohols (eg, cetanol, stearyl alcohol, oleyl alcohol, cholesterol, etc.); ), Water-soluble polymers (for example, carboxyvinyl polymer), higher fatty acids (for example, stearic acid, behenic acid, palmitic acid, oleic acid, etc.) or polyhydric alcohols (for example, propylene glycol, polyethylene glycol, glycerin or 1 , 3-butylene glycol, etc.) and purified water, etc., for example, a cream can be produced by emulsifying while heating and then cooling with stirring.

  When the agent of the present invention is an ointment, for example, fat (for example, pork fat, beef tallow etc.), fatty oil, lanolin, petrolatum (for example white petrolatum, yellow petrolatum etc.), paraffin, wax (for example beeswax etc.) , Resin, plastic (for example, microcrystalline wax, polyethylene powder, etc.), glycols, higher alcohol, glycerin, water, emulsifier, suspending agent or the like as a base, or for example, similar to the above cream An emulsified product can be produced using an emulsified base as a base, adding raspberry ketone to the base and mixing to make the whole quality uniform.

  When the agent of the present invention is a gel, the base component includes, for example, water (for example, purified water, distilled water, etc.), higher alcohol or a gelling agent [for example, carboxyvinyl polymer (Carbopol 941; Noveon, Inc. Etc.) and the like, and the like, and the raspberry ketone together with these base components are heated and dissolved, and cooled with stirring to produce a gel.

  When the agent of the present invention is a liniment, raspberry ketone is added to an additive such as ethanol, fatty oil, glycerin, soap, emulsifier, suspending agent, or a mixture thereof, and an essential oil component such as menthol is added. A liniment can be produced by making the whole into a homogeneous mud.

  Further, when the agent of the present invention is a lotion agent, raspberry ketone and a solvent, an emulsifier or a suspending agent are added to an aqueous liquid, for example, ethanol, fatty oil, glycerin, soap, emulsifier or suspending agent, A lotion preparation can be produced by adding raspberry ketone and mixing to make the whole homogeneous.

  When the agent of the present invention is a poultice, raspberry ketone is mixed with, for example, glycerin, water (for example, purified water, distilled water, etc.), and an essential oil component such as menthol is added to make the whole homogeneous mud. Thus, a poultice can be produced.

Cosmetics such as skin lotions, cosmetic emulsions, cosmetic creams, hand creams, packs, foundations, body soaps, facial cleansers, shampoos, rinses, hair conditioners, hair restorers, etc. are also described above, for example liquids, creams, lotions or It can be produced according to a liniment or the like.
The pack agent may be of a type in which the above-mentioned lotion or emulsion is permeated into, for example, a non-woven fabric and masked on the face or the like, or may be a peel-off type or a cream type that is applied and dried.

In addition, each of the above-mentioned agents of the present invention includes any component that can be used for pharmaceuticals, quasi drugs, cosmetics, and the like, for example, lower alcohols (for example, ethanol, isopropanol, etc.), cooling agents (for example, menthol, camphor, borneol, mint) Oil, camphor, rosemary oil, etc.), wetting agent / humectant (eg, hyaluronic acid, chondroitin sulfate, glycerin, D-sorbitol, propylene glycol, xylitol, sorbit, trehalose, etc.), fragrance (eg, methyl salicylate, fennel) Oil, spruce tincture, dl-menthol, etc.), pH adjusters (eg, hydrochloric acid, citric acid, acetic acid, tartaric acid, sodium bicarbonate, sodium hydroxide, triethanolamine, etc.), preservatives (eg, paraoxybenzoates, Benzyl alcohol, benzalkoni chloride Arm, benzethonium chloride, chlorobutanol, etc.) or a stabilizer (e.g., sodium edetate, ascorbic acid, may be used depending on, for example, required sodium sulfite and the like).
The agent of the present invention, in particular the hair growth or hair growth agent, can contain any active ingredient that can be used in pharmaceuticals, quasi drugs or cosmetics in addition to raspberry ketone and / or its derivatives. Examples of such components include humectants, whitening agents, anti-inflammatory agents, and other hair growth or hair growth agents (such as assembly extracts, capsaicinoids, minoxidil, etc.). By using other hair growth or hair growth agents in combination, synergistic effects due to different action mechanisms can be expected.

(VI) Lip external preparation The lip external preparation of the present invention is an external preparation containing about 0.005 to 0.05 % by weight of raspberry ketone. Since this external preparation contains an effective amount of raspberry ketone, it improves dryness and roughness of the lips, increases gloss or shine, and improves wrinkles. It is also effective in preventing dry and rough lips and wrinkles. The content of raspberry ketone is preferably about 0.0075 to 0.0125% by weight. If it is the said range, the said effect by a raspberry ketone will fully be acquired, and the effect | action which improves dryness and roughness of a lip | rip sufficiently over a long time, increases glossiness or shine, and improves a wrinkle is maintained. Further, when the content of raspberry ketone is about 0.0075 to 0.0125% by weight, the IGF-1 concentration in the skin is maximized, and these actions become more excellent.

Examples of the external preparation include lipstick, lip balm, and lip gloss. Further, it may be a liquid or solid stick type.
Lipsticks, lip balms, and lip glosses can be blended with shape-retaining agents, oils, powders, and the like that are generally blended therein. Examples of the shape-retaining agent include waxes such as polyethylene wax, ceresin wax, carnauba wax, paraffin wax, and microcrystalline wax.
As the oil, in addition to the above liquid oil, for example, hydrocarbon oils such as squalane, liquid paraffin and petrolatum; higher fatty acids such as myristic acid, palmitic acid, stearic acid, 12-hydroxystearic acid and behenic acid; Higher alcohols such as cetyl alcohol, stearyl alcohol, oleyl alcohol, batyl alcohol; cetyl-2-ethylhexanoate, 2-ethylhexyl palmitate, 2-octyldodecyl myristate, neopentyl glycol-2-ethylhexanoate, Esters such as trioctanoic acid glyceride, tetraoctanoic acid pentaerythritol, isopropyl myristate, myristyl myristate, trioleic acid glyceride; olive oil, avocado oil, jojoba oil, sunflower oil, safflower , Oil such as coconut oil, shea fat, macadamia nut oil, mink oil, lanolin, liquid lanolin, lanolin acetate, castor oil; dimethylpolysiloxane, methylphenylpolysiloxane, highly polymerized gum dimethylpolysiloxane, polyether modified silicone And silicone-based oils such as amino-modified silicones and gum-like amino-modified silicones having a high degree of polymerization; and fluorine oils such as perfluoropolyether and perfluorocarbon.

Examples of the powder include inorganic powders such as talc, kaolin, sericite, muscovite, phlogopite, synthetic mica, aluminum silicate, silica, barium sulfate, calcium phosphate, nylon powder, and cellulose powder. In addition to various organic powders, various pigments can be used.
In addition, for example, conventional additives such as antioxidants, ultraviolet absorbers, ultraviolet shielding agents, preservatives, humectants, and dyes can be blended.
The lip external preparation of the present invention can be prepared by mixing raspberry ketone with these components and molding as necessary.

(VII) Method of use The external preparation for skin, the external preparation for lips, and the external preparation for hair growth or hair growth of the present invention may be applied to the skin as it is. In the case of a poultice, it can be applied to the skin after being applied or impregnated on the woven or non-woven fabric layer side of the support, and further a liner such as a polypropylene film is further attached.
The amount of hair growth or hair growth agent used in the case of the external preparation for skin, external preparation for lips, and external preparation of the present invention can be arbitrarily set according to the weight of the user, the form of the external preparation for skin, the application site, etc. . For example, when the raspberry ketone content is about 0.005% by weight, it may be applied about 2 to 10 times a day, and when the raspberry ketone content is about 0.01% by weight, it may be applied about 1 to several times a day.

Although the subject of use is not particularly limited, in the case of a skin external preparation for improving wrinkles or sagging, a person who has wrinkles or sagging on the facial skin is preferable. Moreover, in the skin external preparation for moisturizing, the person whose skins, such as a face, a limb, and lips, are dry or is rough by drying is preferable. In addition, the hair growth or hair growth agent is preferably a person with reduced hair or alopecia. The wound healing promoter is preferably a person who has a wound on the skin. Moreover, the lip external preparation is suitable because it has a preventive effect not only on people with dry and rough lips but also on people with healthy lips.
The present invention also includes a method for improving wrinkles or sagging, a method for retaining skin moisture, hair growth or hair growth, by applying each of the above-described skin external preparations or external preparations to the skin such as the face, limbs, lips, or head. Methods, methods for promoting wound healing, and methods for preventing or improving lip dryness and roughness are also included. The present invention also includes a method for promoting hair growth or hair growth in which the hair growth or hair growth agent described above is administered to a person.

EXAMPLES Hereinafter, the present invention will be described more specifically with reference to examples. However, the present invention is not limited to these examples.
Formulation Example 1 (Liquid)
0.005 g of raspberry ketone was dissolved in 10 g of 99% ethanol, and physiological saline was further added to make the total amount 100 g.
Formulation Example 2 (Liquid)
0.01 g of raspberry ketone was dissolved in 10 g of 99% ethanol, and physiological saline was added to make the total amount 100 g.
Formulation Example 3 (Liquid)
0.05 g of raspberry ketone was dissolved in 10 g of 99% ethanol, and physiological saline was added to make the total amount 100 g.
Formulation Example 4 (Liquid)
0.1 g of raspberry ketone was dissolved in 10 g of 99% ethanol, and physiological saline was further added to make the total amount 100 g.
Formulation Example 5 (Spray Agent)
A composition obtained by mixing 0.01 g of raspberry ketone, 50 g of 99% ethanol and 49.99 g of purified water was filled in a spray container together with carbon dioxide gas to obtain a spray.
Formulation Example 6 (Lotion)
Raspberry ketone-D-glucoside 0.01g
Isopropanol 5g
6g of propylene carbonate
Squalane 4g
Polyoxyethylene hydrogenated castor oil 60.3g
Sorbitan monostearate 1.5g
Carboxy polymer 0.2g
Methyl paraoxybenzoate 0.1g
0.1 g of butyl paraoxybenzoate
Citric acid Appropriate amount Sodium citrate Purified water was added to an appropriate amount or more of components to make the total amount 100 g.
Comparative Formulation Example 1 (Liquid)
Saline was added to 10 g of 99% ethanol to make the total amount 100 g.
<Test Example 1> Skin IGF-1 secretion promoting effect

Six hairless mice were divided into two groups (3 mice each), a raspberry ketone administration group and a control group. In the raspberry ketone administration group, an appropriate amount of the liquid preparation of Formulation Example 2 was applied, and in the control group, the composition of ingredients other than the raspberry ketone was adjusted to be the same as the liquid preparation of Formulation Example 2 without containing raspberry ketone. An appropriate amount of liquid was applied.
After 30 minutes, the subcutaneous tissue was peeled off with scissors, and 100 mg of the entire skin was collected and homogenized in 1 mL of 1N acetic acid. It was centrifuged at 10,000 rpm, 4 ° C. for 10 minutes, and the IGF-1 concentration in the supernatant was measured using enzyme immunoassay. The results are shown in FIG.
From FIG. 1, it can be seen that application of a solution containing 0.01% by weight of raspberry ketone significantly increased the IGF-1 concentration in the skin tissue relative to the control group.
<Test Example 2> Improvement effect of wrinkles or sagging on human face

For volunteer women (30 to 40 years old) who have wrinkles or sagging on their face, in Group 1 (20 people), 1 mL of the liquid of Formulation Example 2 containing 0.01% by weight of raspberry ketone once a day It was applied to the face where there was wrinkle or sagging. Group 2 (10 persons) applied the liquid preparation of Comparative Formulation Example 1 as a control group in the same manner. This was done for a month.
The effect of improving the symptoms of skin wrinkles or sagging before and after application was evaluated by a doctor's photo judgment. The results are shown in Table 1 below. The numerical values in Table 1 indicate the number of persons who determined that the symptom improvement effect was obtained.

From the results shown in Table 1, in Group 1 to which a solution containing 0.01% by weight of raspberry ketone was applied, a marked improvement effect on facial wrinkles or sagging was recognized. Also, as a condition of this test, it was clearly stated that if an undesired phenomenon such as inflammation or skin trouble appears during the use test, the test should be stopped immediately. There was no reaction and no test dropout. That is, it was shown that by applying the liquid preparation containing the raspberry ketone of the present invention, the effect of improving marked wrinkles and sagging can be obtained safely without side effects or adverse effects.
<Test Example 3> Improvement effect of dryness or roughness of human lips

  10 women aged 29-62 who recognize dryness and roughness of lips, apply 0.01% by weight of raspberry ketone to a commercially available lipstick on their lips 3-5 times daily for 14 days. The effect on that was examined. Table 2 below shows the results of the subject's determination of changes in lip state after 14 days. The numbers in Table 2 indicate the number of people who answered that there was a change. The same subject may have made multiple responses.

表３より、ラズベリーケトンを０．０１重量％含有する液剤を塗布したグループ１では、抜け毛に著明な効果が認められた。また、本テストの条件として、テスト中に炎症や肌トラブルなどの好ましくない現象が現れた場合は、速やかにテストを中止することを明記していたが、本テストではこのような好ましくない現象は現れず、テスト脱落者は無かった。即ち、ラズベリーケトンを含有する液剤などを塗布することで副作用や悪影響がなく、安全に、著明な抜け毛改善効果が得られることが示された。
＜試験例６＞人での発毛効果
市販品では全く効果の見られなかった脱毛、薄毛のボランティアの男性及び女性（１０〜５０歳）１０名に、ラズベリーケトンを０．０１重量％含む処方例５のスプレー剤を６ヶ月にわたり使用して貰った。使用方法は、１日１回適量を頭皮にスプレーする方法とした。
その結果、市販の発毛、育毛または養毛剤では全く効果の見られなかった１０名のうち５名において、著明な発毛効果が認められた。また、本テストの条件として、テスト中に炎症や肌トラブルなどの好ましくない現象が現れた場合は、速やかにテストを中止することを明記していたが、本テストではこのような好ましくない現象は現れず、テスト脱落者は無かった。即ち、ラズベリーケトンを含有するスプレー剤などを使用することで副作用や悪影響がなく、安全に、著明な発毛改善効果が得られることが示された。 In addition, all had the impression that the lips were moist, moist and radiant. From these results, it can be seen that by using a lipstick containing 0.01% by weight of raspberry ketone, the dry state of the lips was improved, wrinkles were improved, and the appearance was also moist and bright. In addition, it is thought that the feeling of tension is mainly due to dry lips.
<Test Example 4> Cutaneous IGF-1 Secretion Promoting Effect 25 hairless mice were divided into 5 groups, 4 groups administered with raspberry ketone and 5 control groups. Each group consists of 5 mice. An appropriate amount of the liquid formulation of Formulation Examples 1 to 4 was applied to the raspberry ketone administration group, and an appropriate amount of the liquid formulation of Comparative Formulation Example 1 was applied to the control group. After 30 minutes, the subcutaneous tissue of each group of mice was peeled off with scissors, and 100 mg of the entire skin was collected and treated with dispase, a proteolytic enzyme, for 12 hours to separate the dermis and epidermis. The dermis was homogenized in 1 mL of acetic acid and the epidermis in 0.1 mL of 1 N acetic acid. It was centrifuged at 10,000 rpm, 4 ° C. for 10 minutes, and the IGF-1 concentration in the supernatant was measured by enzyme immunoassay.
The results are shown in FIG. FIG. 2 shows that administration of raspberry ketone significantly increases the IGF-1 concentration in the skin. In particular, when the raspberry ketone concentration was 0.005 to 0.05 wt%, particularly 0.01 wt%, the skin IGF-1 concentration was high.
<Test Example 5> Human hair loss improvement effect 10 volunteer men (30 to 50 years old) with hair loss and thin hair were divided into 2 groups of 5 people per group. A person of group 1 applied an appropriate amount of the liquid of Formulation Example 2 to the scalp once a day. For group 2 people, an appropriate amount of the solution of Comparative Formulation Example 1 was applied to the scalp once a day. This was done for 3 months.
The number of hair loss was measured before the start of application of the liquid, 1 month after the start of application, and 3 months later. The number of hair loss was washed continuously for 4 days, the hair loss for 3 days from 2 to 4 days was collected with a fine mesh and counted. Furthermore, it evaluated on the following references | standards by comparison with the number of hair loss of 3 days measured similarly before the application | coating start.
++++ The number of hair loss decreased by 30 or more, and a remarkable effect was recognized.
++: The number of hair loss decreased by 20 to 29, and a high effect was recognized.
+: The number of hair loss decreased by 10 to 19, and a slight effect was recognized.
±: The number of hair loss is less than 10 or increased, and there is no effect.
The results of averaging the evaluation of each person for each group are shown in Table 3 below.

From Table 3, a remarkable effect on hair loss was observed in Group 1 to which a solution containing 0.01% by weight of raspberry ketone was applied. In addition, as a condition of this test, it was clearly stated that if an undesired phenomenon such as inflammation or skin trouble appears during the test, the test should be stopped immediately. There was no test dropout. That is, it was shown that by applying a liquid containing raspberry ketone, there are no side effects or adverse effects, and a significant effect of improving hair loss can be obtained safely.
<Test Example 6> Human hair growth effect A prescription example containing 0.01% by weight of raspberry ketone in 10 male and female (10 to 50 years old) hair loss and thin hair volunteers who had no effect on commercial products. 5 sprays were used over 6 months. The method of use was a method of spraying an appropriate amount onto the scalp once a day.
As a result, a remarkable hair-growth effect was recognized in 5 out of 10 people who had no effect at all with commercially available hair growth, hair growth or hair nourishing agent. In addition, as a condition of this test, it was clearly stated that if an undesired phenomenon such as inflammation or skin trouble appears during the test, the test should be stopped immediately. There was no test dropout. That is, it has been shown that by using a spray containing raspberry ketone, there are no side effects or adverse effects, and a significant hair growth improving effect can be obtained safely.

  Each agent containing the raspberry ketone of the present invention as an essential component has a function of promoting cell differentiation and proliferation, and promotes secretion of IGF-1 that suppresses the production of inflammatory cytokines such as TNF-α that are enhanced by stress or the like. By doing so, effects such as reduction of wrinkles or sagging of the skin, prevention or reduction of dryness and roughness of the skin of the face and lips, hair growth or hair growth, improvement or treatment of wounds, and the like are exhibited. In addition, it is mild in action, has no side effects, and is highly safe.

It is a figure which shows the IGF-1 density | concentration increase effect in the whole skin layer by a raspberry ketone. It is a figure which shows the IGF-1 density | concentration increase effect in the epidermis and dermis by a raspberry ketone.

Claims (3)

  An agent for hair growth or hair growth containing raspberry ketone.   The agent according to claim 1, which promotes hair growth or hair growth by promoting the secretion of insulin-like growth factor-1.   The agent of Claim 1 or 2 which contains 0.005-0.05 weight% of raspberry ketone with respect to the whole.

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