JP5628574B2 - Cosmetic composition - Google Patents

Description

  The present invention relates to a cosmetic composition that can be suitably used for antiperspirants, skin lotions, hair growth agents, hair growth lotions, hair growth gels, hair growth tonics, hair growth sprays, hair growth tonic sprays and the like.

Substance P is a neuropeptide consisting of 11 amino acids present in the mammalian body. This substance P is induced by stress and is known to be involved in various pathological conditions such as asthma, pain, cough, manic symptoms, migraine, movement disorder, vomiting, and anxiety. In addition, it induces the hair cycle in the rest period, suppresses hair growth (see Non-Patent Document 1), its localization and function, itching, atopic dermatitis, contact dermatitis, psoriasis, urticaria, etc. Involvement in skin diseases has also been reported.
An NK1 receptor (neurokinin 1 receptor) has been identified as a receptor having a high affinity for substance P in vivo, and substance P interacts with the NK1 receptor to transmit intracellular signals. It is known to act as an agonist (agonist) to cause (see Non-Patent Document 2).

In contrast, maltooligosaccharides are known to act as antagonists (antagonists) that can antagonize or block the binding between substance P and the NK1 receptor (see Patent Documents 1 and 2). That is, symptoms such as atopic dermatitis, contact dermatitis, psoriasis or urticaria, asthma, itching and pain can be improved or prevented.
Furthermore, if a maltooligosaccharide and a hair-growth active ingredient corresponding to male pattern baldness can be formulated simultaneously, it is possible to improve or prevent both cases of stress and male pattern baldness.
Therefore, maltooligosaccharides are effective for hair restorer compositions and skin cosmetic compositions.

As active ingredients of skin cosmetics, retinol, β-glycyrrhetinic acid, tocopherol acetate, coenzyme Q10, α lipoic acid and the like are known. However, since these are oil-soluble, it is necessary to be a high-concentration ethanol preparation. is there. The active ingredient of the male hair restorer is also oil-soluble and is often a high-concentration ethanol preparation.
However, when a consumer with symptoms such as sensitive skin uses an alcohol preparation, it may be itchy due to the stimulation of alcohol, and the use of useful skin cosmetics may have to be stopped.

  Therefore, if malto-oligosaccharides, which are NK1 receptor antagonists, can be added to high ethanol cosmetics (lotions, antiperspirants, etc.), a skin cosmetic composition in which itching due to alcohol and other stimuli is suppressed, and stress properties It is possible to provide a hair-restoring agent composition that is effective in both cases of male pattern baldness.

  However, since maltooligosaccharide is a water-soluble substance and a stable substance in an aqueous medium, it has been very difficult to solubilize it in an ethanol preparation containing many poorly water-soluble active ingredients (Patent Documents). 2-3).

  Therefore, the maltooligosaccharide can be used in combination with a sparingly water-soluble active ingredient and can be stably stored without precipitating the maltooligosaccharide, and has excellent depressive effect, male hair loss and stress hair loss. At present, it is desired to provide a cosmetic composition having an effect.

International Publication No. 2008/047709 Specification JP 2009-167134 A JP 2009-249338 A

Eva M.M. J. et al. Peters, et al. , Am J Pathol, 2007, 171 (6), 1872-1886. Kazunari Takayanagi, “From receptors of cell membranes to the latest information”, Nanzando, 1998

  An object of the present invention is to solve the above-described problems and achieve the following objects. That is, the present invention can be used in combination with a maltooligosaccharide and a poorly water-soluble active ingredient, can be stably stored without precipitating the maltooligosaccharide, and has an inhibitory effect, male pattern baldness and stress alopecia An object of the present invention is to provide a cosmetic composition having an excellent hair growth effect.

  In order to solve the above-mentioned problems, the present inventors have made extensive studies and obtained the following findings. That is, by containing at least one of an alkyl ether having a specific polyoxyethylene and an alkyl ether having a polyoxyethylene and a polyoxypropylene, and a dibasic acid diester, an ethanol preparation of 50% by mass or more Malto-oligosaccharides with extremely poor solubility can be solubilized in an ethanol preparation system of 50% to 90% by weight, can be used in combination with oil-soluble hair-growth active ingredients, and specific polyoxy By mixing the alkyl ether having ethylene and at least one of the alkyl ether having polyoxyethylene and polyoxypropylene with a dibasic acid diester at a certain mass ratio, the stability is further high, and an excellent hair growth effect or Finding that it has a depressing effect, and completing the present invention Led was.

The present invention is based on the above findings by the present inventors, and means for solving the above problems are as follows. That is,
<1> (A) hair-growth active ingredient, (B) maltooligosaccharide, (C) alkyl ether having polyoxyethylene, and at least one of alkyl ether having polyoxyethylene and polyoxypropylene, and (D) It contains at least dibasic acid diester and (E) ethanol, and the average addition mole number of ethylene oxide of alkyl ether having polyoxyethylene in the component (C) is 4 to 15, in the component (C) The average addition mole number of the ethylene oxide of the alkyl ether having polyoxyethylene and polyoxypropylene is 4 to 15, the average addition mole number of the propylene oxide is 2 to 6, and the content of the component (E) is It is a cosmetic composition characterized by being 50 mass% to 90 mass%. The
<2> (A) The active ingredient is at least one selected from 6-benzylaminopurine, β-glycyrrhetinic acid, minoxidil, adenosine, pentadecanoic acid monoglyceride, retinol, tocopherol acetate, coenzyme Q10, and α-lipoic acid The cosmetic composition according to <1>.
<3> (D) <1> to <1> above, wherein the dibasic acid diester is at least one selected from dibutyloctyl sebacate, diethylhexyl naphthalenedicarboxylate, diethyl sebacate, diisopropyl sebacate, and diisopropyl adipate 2>. The cosmetic composition according to any one of 2).
<4> (B) The cosmetic composition according to any one of <1> to <3>, wherein the malto-oligosaccharide is a disaccharide to 9-saccharide oligosaccharide.
<5> The cosmetic composition according to any one of <1> to <4>, wherein the content of (B) maltooligosaccharide is 0.01% by mass to 10% by mass.
<6> The above <1>, wherein the content of at least one of (C) an alkyl ether having polyoxyethylene and an alkyl ether having polyoxyethylene and polyoxypropylene is 0.05% by mass to 10% by mass. To <5>.
<7> (D) <1> to <6>, wherein the dibasic acid diester is at least one of dibutyloctyl sebacate, diethylhexyl naphthalenedicarboxylate, diethyl sebacate, diisopropyl sebacate, and diisopropyl adipate The cosmetic composition according to any one of the above.
<8> The cosmetic composition according to any one of <1> to <7>, wherein the content of (D) dibasic acid diester is 0.01% by mass to 5% by mass.
<9> (C) The mass ratio of the alkyl ether having polyoxyethylene and the content of at least one of the alkyl ether having polyoxyethylene and polyoxypropylene and the content of (D) dibasic acid diester Is a cosmetic composition according to any one of <1> to <8>, wherein (C) / (D) = 1 to 50.
<10> The component (A) is at least one selected from 6-benzylaminopurine, β-glycyrrhetinic acid, minoxidil, adenosine, and pentadecanoic acid monoglyceride, from the above <1> used as a hair restorer composition <9> The cosmetic composition according to any one of the above.
<11> The cosmetic composition according to <10>, which is used for at least one of androgenetic alopecia and stress alopecia.
<12> The component (A) is at least one selected from retinol, tocopherol acetate, coenzyme Q10, and α-lipoic acid, and any one of <1> to <9> used as a skin cosmetic composition The cosmetic composition described in 1.

  According to the present invention, the conventional problems can be solved, the object can be achieved, and the maltooligosaccharide and a sparingly water-soluble active ingredient can be used together, and the maltooligosaccharide can be stably stored without precipitation. It is possible to provide a cosmetic composition that has a depressing effect and a hair-growth effect excellent in male pattern alopecia and stress alopecia.

(Cosmetic composition)
The cosmetic composition of the present invention comprises (A) an active ingredient, (B) a maltooligosaccharide, (C) an alkyl ether having polyoxyethylene (hereinafter sometimes referred to as “POE”), and POE. And at least one of alkyl ethers having polyoxypropylene (hereinafter sometimes referred to as “POP”), (D) a dibasic acid diester, and (E) ethanol, and if necessary, Furthermore, other components are contained.

<(A) component>
The component (A) is not particularly limited as long as it is an active ingredient that is hardly soluble in water and soluble in ethanol, and can be appropriately selected according to the purpose. 6-benzylaminopurine, β-glycyrrhetinic acid, minoxidil, adenosine, pentadecanoic acid monoglyceride, retinol, coenzyme Q10 (CoQ10), tocopherol acetate, α lipoic acid and the like are more preferable. These may be used alone or in combination of two or more.
Among these, as an active ingredient of the hair restorer composition, a drug that improves suppression of hair growth by male hormones is preferable, and at least one of 6-benzylaminopurine, β-glycyrrhetinic acid, minoxidil, adenosine, and pentadecanoic acid monoglyceride It is more preferable that at least one of 6-benzylaminopurine and pentadecanoic acid monoglyceride is particularly preferable because of its high stability and hair-restoring effect.
Moreover, as an active ingredient of a skin cosmetic composition, retinol, coenzyme Q10, tocopherol acetate, alpha lipoic acid, etc. are preferable.

There is no restriction | limiting in particular as an acquisition method of the said (A) component, According to the objective, it can select suitably, For example, the method of synthesize | combining, the method of using a commercial item, etc. are mentioned.
Specific examples of the commercially available products include 6-benzylaminopurine (manufactured by Sansho Pharmaceutical Co., Ltd.), β-glycyrrhetinic acid (manufactured by Maruzen Pharmaceutical Co., Ltd.), minoxidil (manufactured by Sigma Aldrich Japan Co., Ltd.), adenosine (Sigma Aldrich Japan Co., Ltd.) Company), pentadecanoic acid monoglyceride (manufactured by Lion Chemical Co., Ltd.), retinol (BASF Japan), tocopherol acetate (DSM Nutrition Japan Co., Ltd.), CoQ10 (manufactured by Kyowa Hakko Bio Co., Ltd.), α lipoic acid (Oryza Oil & Chemical Co., Ltd. Manufactured).

  There is no restriction | limiting in particular as content of the said (A) component in the said cosmetic composition, Although it can select suitably according to the objective, 0.01 mass%-5 mass% are preferable, and 0.05 mass % To 2.5% by mass is more preferable. When the content of the component (A) is less than 0.01% by mass, a desired effect (for example, a hair-growth effect or an antioxidant effect) by the component (A) may not be obtained. When it exceeds%, the stability deteriorates, and the effect of the component (A) may not be obtained due to the precipitation of the component (A).

<(B) component>
The malto-oligosaccharide as the component (B) is a compound having an NK1 receptor antagonistic action and an action of suppressing hair loss and itch caused by substance P induced by stress. Moreover, the said (B) component is preferable at the point which is a highly safe compound which can be used also for foodstuffs.

There is no restriction | limiting in particular as said (B) component, According to the objective, it can select suitably, For example, maltose (disaccharide), maltotriose (trisaccharide), maltotetraose (tetrasaccharide), maltopenta Examples include oose (pentasaccharide), maltohexaose (hexasaccharide), maltoheptaose (sucrose), maltooctaose (octasaccharide), maltononaose (nine sugar) and the like. These may be used alone or in combination of two or more.
Among these, the component (B) is preferably a disaccharide to 9 sugar oligosaccharide, more preferably a trisaccharide to 6 sugar, and particularly preferably a tetrasaccharide to 5 sugar.

  The method for obtaining the component (B) is not particularly limited and may be appropriately selected depending on the intended purpose. Examples thereof include a synthesis method, a method obtained by allowing an enzyme to act on starch, and a method using a commercially available product. Is mentioned.

  There is no restriction | limiting in particular as content of the said (B) component in the said cosmetics composition, It can select suitably according to usage, a dosage form, age, sex, other conditions, the grade of a symptom of a user, etc. However, 0.01 mass%-10 mass% are preferable, and 0.1 mass%-5 mass% are more preferable. When the content of the component (B) is less than 0.01% by mass, a sufficient hair-growth effect or an inhibitory effect may not be obtained, and when it exceeds 10% by mass, the stability is deteriorated. (B) A sufficient hair-growth effect and an inhibitory effect may not be acquired by precipitation of a component.

<(C) component>
The alkyl ether having POE as the component (C) and the alkyl ether having POE and POP are blended for the purpose of stabilizing the component (B).

-Alkyl ether having POE-
The average number of added moles of ethylene oxide of the alkyl ether having POE (hereinafter sometimes referred to as “EO”) is 4 to 15, but 6 to 12 is preferable from the viewpoint of stability.
There is no restriction | limiting in particular as an alkyl group in the alkyl ether which has the said POE, Although it can select suitably according to the objective, A 10-24 linear or branched chain is preferable.

There is no restriction | limiting in particular as the acquisition method of the alkyl ether which has the said POE, According to the objective, it can select suitably, For example, the method of synthesize | combining, the method of using a commercial item, etc. are mentioned.
Specific examples of the commercially available products include polyoxyethylene lauryl ether (Laureth-4 (EO: 4), trade name: NIKKOL BL-4.2), polyoxyethylene lauryl ether (Laureth-9 (EO: 9)), Product name: NIKKOL BL-9EX), polyoxyethylene cetyl ether (ceteth-6 (EO: 6), product name: NIKKOL BC-5.5), polyoxyethylene cetyl ether (ceteth-7 (EO: 7)), Product name: NIKKOL BC-7), polyoxyethylene cetyl ether (ceteth-10 (EO: 10), product name: NIKKOL BC-10), polyoxyethylene oleyl ether (Oles-7 (EO: 7), product name : NIKKOL BO-7V), polyoxyethylene oleyl ether (Oles-10 (EO: 10)), Product name: NIKKOL BO-10V), polyoxyethylene behenyl ether (Beneness-10 (EO: 10), product name: NIKKOL BB-10), polyoxyethylene cetyl ether (ceteth-15 (EO: 15), product) Name: NIKKOL BC-15) (all manufactured by Nikko Chemicals Co., Ltd.). These may be used alone or in combination of two or more.

-Alkyl ether having POE and POP-
The alkyl ether having POE and POP is a block type nonion obtained by addition polymerization of ethylene oxide and propylene oxide to a linear or branched aliphatic alcohol having a carbon chain length of 4 to 24, more preferably 10 to 24. Active activator.
The alkyl ether having POE and POP has an EO average addition mole number of 4 to 15 and a propylene oxide (hereinafter sometimes referred to as “PO”) average addition mole number of 2 to 6, From the viewpoint of stability, the EO average added mole number is preferably 6 to 12, and the PO added mole number is preferably 2 to 6.

The method for obtaining the component (C) is not particularly limited and may be appropriately selected depending on the intended purpose. Examples thereof include a synthesis method and a commercially available method.
Specific examples of the commercially available products include polyoxyethylene polyoxypropylene decyl ether (PPG-2-deces-7 (EO: 7, PO: 2), trade name: EMALEX DAPE-0207), polyoxyethylene polyoxypropylene Decyl ether (PPG-2-deceth-10 (EO: 10, PO: 2), trade name: EMALEX DAPE-0210), polyoxyethylene polyoxypropylene decyl ether (PPG-2-deceth-12 (EO: 12, PO: 2), trade name: EMALEX DAPE-0212), polyoxyethylene polyoxypropylene lauryl ether (PPG-5 laureth-6 (EO: 6, PO: 5), trade name: Nonion A-10R), polyoxy Ethylene polyoxypropylene cetyl ether (PPG-4 ceteth 10 (EO: 10, PO: 4), trade name: NIKKOL PBC-33), polyoxyethylene polyoxypropylene decyl tetradecyl ether (PPG-6 decyl tetradeces-12 (EO: 12, PO: 6), Product name: NIKKOL PEN-4612) (all manufactured by Nikko Chemicals Co., Ltd.). These may be used alone or in combination of two or more.

  There is no restriction | limiting in particular as content of the said (C) component in the said cosmetic composition, Although it can select suitably according to the objective, 0.05 mass%-10 mass% are preferable, 0.1 mass % To 5% by mass is more preferable. When the content of the component (C) is less than 0.05% by mass or exceeds 10% by mass, the stability is deteriorated, and sufficient hair-growth effect or suppression effect cannot be obtained by precipitation of the component (B). Sometimes.

<(D) component>
The dibasic acid diester that is the component (D) is blended for the purpose of stabilizing the component (B).
The component (D) is not particularly limited and may be appropriately selected depending on the intended purpose, but at least of dibutyl octyl sebacate, diethyl hexyl naphthalenedicarboxylate, diethyl sebacate, diisopropyl sebacate, and diisopropyl adipate Either is preferred.

The method for obtaining the component (D) is not particularly limited and may be appropriately selected depending on the intended purpose. Examples thereof include a synthesis method and a commercially available method.
Specific examples of the commercially available products include dibutyloctyl sebacate (trade name: DS-1220, Nikko Chemicals Co., Ltd.), diethylhexyl naphthalenedicarboxylate (trade name: CORAPAN TQ, Nikko Chemicals Co., Ltd.), diethyl sebacate (product) Name: NIKKOL DES-SP), diisopropyl sebacate (trade name: NIKKOL DIS), diisopropyl adipate (trade name: NIKKOL DID), and the like.
Among these, the component (D) is particularly preferably dibutyloctyl sebacate or diethylhexyl naphthalene dicarboxylate, which is a diester composed of a dibasic acid and a 2-alkyl-alkanol, because of its high stability.

  There is no restriction | limiting in particular as content of said (D) component, Although it can select suitably according to the objective, 0.01 mass%-5 mass% are preferable, and 0.1 mass%-2 mass% are preferable. More preferred. When the content of the component (D) is less than 0.01% by mass or exceeds 5% by mass, the stability is deteriorated, and sufficient hair-growth effect or suppression effect cannot be obtained by precipitation of the component (B). Sometimes.

<(E) component>
Ethanol as the component (E) is blended for the purpose of dissolving the component (A).
The content of the component (E) in the cosmetic composition is preferably 50% by mass to 90% by mass. When the content of the component (E) is less than 50% by mass, the component (A) may be precipitated, and a sufficient hair-growth effect or an inhibitory effect may not be obtained. When the content exceeds 90% by mass, The component (B) may precipitate and a sufficient hair-growth effect or suppressive effect may not be obtained.

<(C) / (D) (mass ratio)>
The mass ratio ((C) / (D)) between the content of the component (C) and the content of the component (D) is not particularly limited and can be appropriately selected according to the purpose. 1-50 are preferable and 2-20 are more preferable. When the mass ratio is outside the above preferred range, the stability is deteriorated, and sufficient hair-growth effect or suppression effect may not be obtained due to precipitation of the component (B).

<Other ingredients>
The other components are not particularly limited and can be appropriately selected as necessary within the range not impairing the effects of the present invention. For example, water (purified water, distilled water, ion-exchanged water, pure water, Pure water, deep sea water, etc.), polyhydric alcohol, nonionic surfactants excluding component (C), other surfactants such as amphoteric surfactants, celluloses, vegetable oils, excluding component (D) Ester oil, keratolytic agent, polymer resin, colorant, fragrance, ultraviolet absorber, vitamins excluding the component (A), vasodilator, cell activator, amino acids, anti-inflammatory agent, skin function enhancer, etc. And other medicinal ingredients.

  The polyhydric alcohol is not particularly limited and may be appropriately selected depending on the intended purpose. Examples thereof include glycerin, xylitol, sorbitol, 1,3-butylene glycol, propylene glycol, and polyethylene glycol.

  There is no restriction | limiting in particular as said cellulose, According to the objective, it can select suitably, For example, a hydroxymethylcellulose, a hydroxypropyl cellulose, a hydroxypropyl methylcellulose etc. are mentioned.

  There is no restriction | limiting in particular as nonionic surfactant except the said (C) component, According to the objective, it can select suitably, For example, sorbitan fatty acid ester (Sorbitan monolaurate, sorbitan monooleate, etc.), poly Examples thereof include oxyethylene hydrogenated castor oil, polyoxyethylene hydrogenated castor oil mono- or isostearate, glycerin fatty acid ester, polyglycerin fatty acid ester (monomyristic acid decaglycerin, monomyristic acid pentaglycerin, and the like).

  There is no restriction | limiting in particular as ester oil except the said (D) component, According to the objective, it can select suitably, For example, polyhydric alcohols, such as tri-2 ethylhexanoic acid glycerin and triisostearic acid trimethylol propanoic acid Examples include fatty acid esters.

  The vegetable oil is not particularly limited and may be appropriately selected depending on the intended purpose. For example, eucalyptus oil, safflower oil, evening primrose oil, jojoba oil, unsaturated fatty acid alkyl ester (ethyl oleate, isopropyl linoleate, etc.) ), Methyl myristate, isopropyl myristate and the like.

  The keratolytic agent is not particularly limited and may be appropriately selected depending on the intended purpose. Examples thereof include salicylic acid and resorcin.

  There is no restriction | limiting in particular as said polymeric resin, According to the objective, it can select suitably, For example, an amphoteric polymer, a cationic polymer, an anionic polymer, a nonionic polymer etc. are mentioned.

  The ultraviolet absorber is not particularly limited and may be appropriately selected depending on the intended purpose. Examples thereof include octyl methoxycinnamate (Neoheliopan AV), oxybenzone and urocanic acid.

<Mixed or combined>
The cosmetic composition may be used alone or in combination with a cosmetic composition containing other ingredients as active ingredients, or a cosmetic containing other ingredients as active ingredients. You may use it in the state mix | blended in the composition.

<Dosage form>
There is no restriction | limiting in particular as a dosage form of the said cosmetics composition, According to the objective, it can select suitably, For example, a solution, an emulsion, a lotion, a gel, an external preparation, an aerosol agent etc. are mentioned.
When the cosmetic composition is an aerosol, in addition to the above components, lower alcohols such as n-propyl alcohol and isopropyl alcohol; flammable gases such as butane, propane, isobutane, liquefied petroleum gas, and dimethyl ether; nitrogen gas, oxygen A compressed gas such as gas, carbon dioxide gas, and nitrous oxide gas can be contained.

<Manufacturing method>
There is no restriction | limiting in particular as a manufacturing method of the said cosmetics composition, According to dosage form etc., it can select from the conventional methods suitably.

<Use>
There is no restriction | limiting in particular as the usage method of the said cosmetics composition, usage-amount, and the frequency | count of use, According to dosage form, the kind of said (A) component, age of a user, sex, other conditions, the grade of a symptom, etc. Can be selected as appropriate.
The animal species to be used for the cosmetic composition is preferably used for humans, but is not limited thereto, for example, monkeys, pigs, cows, sheep, goats, dogs, cats, Animal species such as mice, rats, and birds may be used.

<Application>
The cosmetic composition can be used in combination with maltooligosaccharide and a sparingly water-soluble active ingredient, and can be stored stably without precipitating the maltooligosaccharide, and has an inhibitory effect, androgenetic alopecia and stress hair loss Suitable for skin cosmetic compositions such as antiperspirants, skin lotions, hair growth agents, hair growth lotions, hair growth gels, hair growth tonics, hair growth sprays, hair growth tonic sprays, etc. Is available.

  EXAMPLES The present invention will be specifically described below with reference to examples of the present invention, but the present invention is not limited to these examples. In the following Examples and Comparative Examples, “%” represents “% by mass” unless otherwise specified, and each component amount represents a value converted into a pure component.

(Examples 1-44, Comparative Examples 1-13)
According to the composition shown in Tables 1-8, each hair restorer composition was prepared by a conventional method. With respect to the hair growth agent compositions of Examples 1 to 44 and Comparative Examples 1 to 13 that were prepared, the stability and evaluation of the hair growth effect by the male pattern alopecia model system and the stress alopecia model system were performed by the methods described below. went.

<Evaluation of stability>
Immediately after compounding each of the hair restorer compositions of Examples 1 to 44 and Comparative Examples 1 to 13, about 50 mL was filled in a 50 mL transparent vial and stored at −10 ° C. for 10 days. Evaluation was made according to the criteria.
-Criteria-
A: Appearance is transparent.
○: Appearance is slightly cloudy, but no precipitate is observed.
(Triangle | delta): The appearance is cloudy and a small deposit is recognized.
X: The appearance is turbid and there are many precipitates.

<Hair restoration effect>
<< Male pattern baldness model system >>
Using C3H mice (male, 7 weeks old, Nippon SLC Co., Ltd., n = 8) in the rest period of the hair cycle, the method of Ogawa et al. (Fragrance Journal, 1989, Vol. 17, No. 5, P. 20). -29). That is, the entire back of the mouse was removed with an electric clipper and an electric shaver (day 0). From the next day, hair restoration compositions of Examples 1 to 44 and Comparative Examples 1 to 13 were applied once a day at 100 μL, 5 times a week for 16 days. Rearing was carried out in a specific pathogen free (SPF) environment.
For each mouse, the ratio of the hair regeneration area to the hair removal area on the 16th day after hair removal is determined from the following formula, and based on the following judgment criteria, “remarkable”, “effective”, “invalid” are judged, and the following evaluation is performed. Evaluation was performed based on the criteria. The results are shown in Tables 1-8.
Ratio of hair regeneration area (%) = (Hair removal area on day 0−Hair removal area on day 16 after hair removal) / Hair removal area on day 0 × 100

-Criteria-
Remarkable: Ratio of hair regeneration area is over 70% Effective: Ratio of hair regeneration area is 50% or more and 70% or less Invalid: Ratio of hair regeneration area is less than 50% -Evaluation criteria-
A: Six or more effective cases and no invalid cases.
○: 2 or more and less than 5 effective cases, and no invalid cases.
(Triangle | delta): There are an ineffective example with 1 or more and less than 5 effective examples.
X: There is no remarkable effect.

<< Stressed alopecia model system >>
Using C57BL / 6 mice (male, 7 weeks old, SLC Japan, n = 8) in the rest period of the hair cycle, Eva Milena J. et al. The test was conducted according to the method of Peters et al. (Refer to American Journal of Pathology, 2004, Vol. 165, No. 1, July, P. 259-271). That is, the entire back of the mouse was removed with an electric clipper and an electric shaver (day 0). From the next day, hair restoration compositions of Examples 1 to 44 and Comparative Examples 1 to 13 were applied 100 μL once a day, 5 times a week for 16 days, respectively. During the breeding period, an ultrasonic generator for extermination of mice (Pescontron; manufactured by Rentec International Inc.) was installed in the breeding room, and ultrasonic waves were generated at intervals of 1 minute for 16 days to give stress to the mice. Rearing was performed in an SPF environment.
For each mouse, the ratio of the hair regeneration area to the hair removal area on the 16th day after hair removal was calculated by the same method as the test of the male pattern baldness model system, and the same method as the test of the male pattern baldness model system Was evaluated. The results are shown in Tables 1-8.

  From the results of Comparative Examples 1 to 13, when the (C) component and the (D) component are not used together (Comparative Examples 3 and 9), the average EO addition mole number in which the (C) component is within the range of the present invention is 4 to 15. Is not satisfied (Comparative Examples 4 to 5), or when the average EO addition mole number is 4 to 15 and the average PO addition mole number is 2 to 6 (Comparative Examples 6 to 8), and the component (D) is present. In the case of dibasic acid diesters other than the invention or other fatty acid esters (component (D ′)) (Comparative Examples 10 and 11), the stability at low temperature is poor, and precipitation of component (B) is observed and transparent. It was found that a liquid appearance could not be obtained and sufficient hair-growth effect could not be obtained due to precipitation of the component (A) and the component (B).

On the other hand, in Examples 1-44, by containing (A) component, (B) component, (C) component, (D) component, and (E) component in the range of this invention, favorable stability is contained. It was also found that a hair growth effect can be obtained.
In addition, when each component was mix | blended within the following range, it turned out that it is excellent in stability and a transparent liquid external appearance is obtained, and a favorable hair growth effect is acquired.
(A) 0.01 mass%-5 mass% are preferable, and 0.05 mass%-2.5 mass% were more preferable.
(B) 0.01 mass%-10 mass% were preferable, and 0.1 mass%-5 mass% were more preferable.
Component (C) is preferably 0.05% by mass to 10% by mass, and more preferably 0.1% by mass to 5% by mass.
The component (D) is preferably 0.01% by mass to 5% by mass, and more preferably 0.1% by mass to 2% by mass.
Furthermore, (C) / (D) = 1-50 were preferable and, as for mass ratio of content of (C) component and content of (D) component, 2-20 were more preferable.
(E) 50 mass%-90 mass% of the component was preferable.

  Specific examples in which the hair-restoring agent composition exhibiting excellent hair-growth effects are applied to actual products are shown below. In addition, the hair restorer composition of the following Examples 45-55 was prepared according to the usual method of each dosage form according to each composition. Moreover, about the following Examples 45-55, the result of having performed evaluation similar to the said Examples 1-44 is also shown below.

(Example 45: Hair restorer)
-Composition-
6-Benzylaminopurine (component (A)) 0.5%
Maltotetraose (component (B)) 1.0%
PPG-6decyltetradeces-12 (EO: 12, PO: 6) (component (C))
2.0%
Dibutyloctyl sebacate (component (D)) 0.5%
Propylene glycol 3.0%
Sucrose myristic acid ester 0.5%
Succinic acid 0.3%
L-Menthol 0.3%
Fragrance 0.05%
Methylparaben 0.1%
Ethanol (component (E)) 70.0%
Purified water balance 100.0%
(C) / (D) = 4 (mass ratio)
Stability: ◎
Hair growth effect Male hair loss: ◎
Stress hair loss: ◎

(Example 46: Hair restorer)
-Composition-
6-Benzylaminopurine (component (A)) 0.5%
Pentadecanoic acid monoglyceride (component (A)) 2.5%
Maltotetraose (component (B)) 1.0%
PPG-6decyltetradeces-12 (EO: 12, PO: 6) (component (C))
2.0%
Dibutyloctyl sebacate (component (D)) 0.5%
Propylene glycol 3.0%
Sucrose myristic acid ester 0.5%
Succinic acid 0.3%
L-Menthol 0.3%
Fragrance 0.05%
Ethanol (component (E)) 70.0%
Purified water balance 100.0%
(C) / (D) = 4 (mass ratio)
Stability: ◎
Hair growth effect Male hair loss: ◎
Stress hair loss: ◎

(Example 47: Hair growth lotion)
-Composition-
Pentadecanoic acid monoglyceride (component (A)) 2.5%
Maltotetraose (component (B)) 1.0%
PPG-6decyltetradeces-12 (EO: 12, PO: 6) (component (C))
2.0%
Dibutyloctyl sebacate (component (D)) 0.5%
Propylene glycol 3.0%
Nicotinamide 0.1%
L-Menthol 0.5%
Fragrance 0.5%
Ethanol (component (E)) 85.0%
Purified water balance 100.0%
(C) / (D) = 4 (mass ratio)
Stability: ◎
Hair growth effect Male hair loss: ◎
Stress hair loss: ◎

(Example 48: Hair growth gel)
-Composition-
6-Benzylaminopurine (component (A)) 0.5%
β-glycyrrhetinic acid (component (A)) 0.05%
Marto Tetraose (component (B)) 3.0%
Laureth-9 (EO: 9) (component (C)) 2.0%
Diethylhexyl naphthalene dicarboxylate (component (D)) 1.0%
Propylene glycol 3.0%
L-Menthol 0.5%
Amino-modified silicone (2) 2.0%
Stearyltrimethylammonium chloride 2.5%
Tetraglyceryl monoisostearate 5.0%
Tetraoleic acid polyoxyethylene (40) sorbit 0.5%
Dihydroxybenzophenone 0.1%
Hydroxyethyl cellulose 0.5%
Sodium pyrophosphate anhydrous 0.2%
Fragrance 0.5%
Ethanol (component (E)) 70.0%
Purified water balance 100.0%
(C) / (D) = 2 (mass ratio)
Stability: ◎
Hair growth effect Male hair loss: ◎
Stress hair loss: ◎

(Example 49: Hair growth tonic)
-Composition-
6-Benzylaminopurine (component (A)) 0.5%
Maltotetraose (component (B)) 1.0%
PPG-4 ceteth-10 (EO: 10 PO: 4) (component (C)) 2.0%
Dibutyloctyl sebacate (component (D)) 0.2%
Propylene glycol 3.0%
Stearoyl dioctyldodecyl glutamate 2.0%
Polyoxyethylene stearyl ether (20EO) 2.0%
POP (70) glyceryl ether 5.0%
Isopropyl myristate 3.0%
L-Menthol 0.2%
Citric acid 0.1%
Dibutylhydroxytoluene 0.01%
Fragrance 0.05%
Ethanol (component (E)) 80.0%
Purified water balance 100.0%
(C) / (D) = 10 (mass ratio)
Stability: ◎
Hair growth effect Male hair loss: ◎
Stress hair loss: ◎

(Example 50: Hair growth tonic)
-Composition-
6-Benzylaminopurine (component (A)) 0.5%
Maltotetraose (component (B)) 1.0%
Maltopentaose (component (B)) 1.0%
PPG-4 ceteth-10 (EO: 10 PO: 4) (component (C)) 2.0%
Dibutyloctyl sebacate (component (D)) 0.2%
Propylene glycol 3.0%
Stearoyl dioctyldodecyl glutamate 2.0%
Polyoxyethylene stearyl ether (20EO) 2.0%
POP (70) glyceryl ether 5.0%
Isopropyl myristate 3.0%
L-Menthol 0.2%
Fragrance 0.05%
Ethanol (component (E)) 80.0%
Purified water balance 100.0%
(C) / (D) = 10 (mass ratio)
Stability: ◎
Hair growth effect Male hair loss: ◎
Stress hair loss: ◎

(Example 51: Hair growth tonic)
-Composition-
6-Benzylaminopurine (component (A)) 0.5%
Maltotetraose (component (B)) 1.0%
PPG-4 ceteth-10 (EO: 10 PO: 4) (component (C)) 2.0%
PPG-6decyltetradeces-12 (EO: 12, PO: 6) (component (C))
2.0%
Dibutyloctyl sebacate (component (D)) 0.2%
Propylene glycol 3.0%
Piroctone olamine 0.1%
POP (70) glyceryl ether 5.0%
Isopropyl myristate 3.0%
L-Menthol 0.2%
Citric acid 0.1%
Dibutylhydroxytoluene 0.01%
Fragrance 0.05%
Ethanol (component (E)) 80.0%
Purified water balance 100.0%
(C) / (D) = 20 (mass ratio)
Stability: ◎
Hair growth effect Male hair loss: ◎
Stress hair loss: ◎

(Example 52: Hair growth tonic)
-Composition-
6-Benzylaminopurine (component (A)) 0.5%
Maltotetraose (component (B)) 1.0%
PPG-2 Cedes-10 (EO: 10 PO: 2) (component (C)) 2.0%
Dibutyloctyl sebacate (component (D)) 0.2%
Diethylhexyl naphthalenedicarboxylate (component (D)) 0.2%
Propylene glycol 3.0%
Stearoyl dioctyldodecyl glutamate 2.0%
Polyoxyethylene stearyl ether (20EO) 2.0%
POP (70) glyceryl ether 5.0%
Isopropyl myristate 3.0%
L-Menthol 0.2%
Citric acid 0.1%
Dibutylhydroxytoluene 0.01%
Fragrance 0.05%
Ethanol (component (E)) 80.0%
Purified water balance 100.0%
(C) / (D) = 5 (mass ratio)
Stability: ○
Hair growth effect Male pattern hair removal: ○
Stress hair loss: ○

(Example 53: Hair growth spray)
-Composition-
[Undiluted solution]
6-Benzylaminopurine (component (A)) 0.5%
Maltotetraose (component (B)) 1.0%
Ores-7 (EO: 7) (component (C)) 3.0%
Dibutyloctyl sebacate (component (D)) 0.2%
Propylene glycol 3.0%
Pyroglutamic acid isostearic acid POE (40) hydrogenated castor oil 1.5%
POP (24) Glyceryl ether 12.0%
Ethyl oleate 0.1%
Citric acid 0.3%
Sucrose laurate 0.5%
Fragrance 0.1%
L-menthol 0.1%
Ethanol (component (E)) 60.0%
Purified water balance 100.0%
[Hair growth spray]
Stock solution 80.0%
LPG 20.0%
Total 100.0%
(C) / (D) = 15 (mass ratio)
Stability: ◎
Hair growth effect Male hair loss: ◎
Stress hair loss: ◎

(Example 54: Hair growth tonic spray)
[Undiluted solution]
6-Benzylaminopurine (component (A)) 0.5%
Maltotetraose (component (B)) 1.0%
PPG-6decyltetradeces-12 (EO: 12, PO: 6) (component (C))
5.0%
Diethylhexyl naphthalenedicarboxylate (component (D)) 0.3%
Propylene glycol 3.0%
Stearyltrimethylammonium chloride 0.1%
POP (67) glyceryl ether 20.0%
Polyethylene glycol 300 0.5%
Pyroglutamate oleic acid glyceryl 1.5%
L-Menthol 0.5%
Fumaric acid 0.05%
Fragrance 0.01%
Ethanol (component (E)) 60.0%
Purified water balance 100.0%
[Hair growth spray]
Stock solution 84.5%
DME 15.0%
Nitrogen 0.5%
Total 100.0%
(C) / (D) = 16.7 (mass ratio)
Stability: ◎
Hair growth effect Male hair loss: ◎
Stress hair loss: ◎

(Example 55: Hair growth tonic spray)
[Undiluted solution]
6-Benzylaminopurine (component (A)) 0.5%
Minoxidil (component (A)) 1.0%
Marto Tetraose (component (B)) 2.0%
PPG-6decyltetradeces-12 (EO: 12, PO: 6) (component (C))
2.0%
Dibutyloctyl sebacate (component (D)) 0.5%
Propylene glycol 3.0%
Lauroylglutamate dihexyldecyl 1.0%
POP (70) glyceryl ether 17.0%
L-Menthol 0.2%
Citric acid 0.05%
Ethanol (component (E)) 60.0%
Purified water balance 100.0%
[Hair growth spray]
Stock solution 84.5%
LPG 15.0%
Nitrogen 0.5%
Total 100.0%
(C) / (D) = 4 (mass ratio)
Stability: ◎
Hair growth effect Male hair loss: ◎
Stress hair loss: ◎

(Examples 56 to 72, Comparative Examples 14 to 17)
According to the compositions shown in Tables 9 to 12, each cosmetic composition was prepared by a conventional method. The prepared cosmetic compositions of Examples 56 to 72 and Comparative Examples 14 to 17 were evaluated for stability and suppression effect by a sensitive skin model system by the methods described below.

<Evaluation of stability>
Immediately after compounding the cosmetic compositions of Examples 56 to 72 and Comparative Examples 14 to 17, about 50 mL was filled in a 50 mL transparent vial and stored at −10 ° C. for 10 days. Evaluation was made according to the criteria.
-Criteria-
A: Appearance is transparent.
○: Appearance is slightly cloudy, but no precipitate is observed.
(Triangle | delta): The appearance is cloudy and a small deposit is recognized.
X: The appearance is turbid and there are many precipitates.

<Depressive effect>
<< sensitive skin model system >>
Using HOS: HR-1 (female, 4 weeks old, Nippon SLC Co., Ltd., n = 10) as a hairless mouse, special food HR-AD (manufactured by Nippon Agricultural Industrial Co., Ltd.) is given by free intake, and sensitive skin is obtained. Induced.

−Pretreatment by inserting magnets−
One week after the start of breeding of the sensitive skin-inducing mouse, the mouse's hind limb anesthetized with somnopentyl was incised with a surgical scissors about 2 mm, and a small magnetic chip (length 2 mm × diameter 1 mm in diameter) was subcutaneously inserted into the incision. , Manufactured by Neuroscience Co., Ltd.), and the wound was joined with Aron α. Thereafter, the animals were reared under the same conditions as described above for 8 weeks.

-Measure the number of scratches-
70 μL of each of the cosmetic compositions of Examples 56 to 72 and Comparative Examples 14 to 17 was applied to the face, armpit, and back of the sensitive skin-inducing mouse (13 weeks old) using a paint brush. As a base, 70% by volume ethanol containing 10% by mass N-methyl-2-pyrrolidone was used. After application, the mouse is once returned to the cage for breeding and acclimated for 2 hours, and then one mouse is placed from the cage to the acrylic tube for measurement, and an automatic measuring device for the number of scratches (Micro Act, manufactured by Neuroscience Co., Ltd.) ). The number of scratches was measured in an unattended environment, and analysis was performed with Micro Act Analysis ver1.06 (manufactured by Neuroscience). The number of scratching operations was recorded by counting the number of scratching motions by the hind limbs counted in one hour, assuming that the continuous scratching motion (bout) from the start of scratching to lowering the hind limb was once (= 1 bout).
Moreover, it replaced with said each cosmetics composition, the group which apply | coated only the said base material was made into the control group, and the frequency | count of scratching was measured by the same method as the above.
From the measurement results, the reduction rate of the number of scratches was determined from the following formula, and the suppression effect was evaluated based on the following evaluation criteria. The results are shown in Tables 9-12.
Reduction rate of number of scratches (%) = (A−B) / B × 100
In the above formula, “A” represents the number of scratches of the control group to which only the base material was applied, and “B” represents the number of scratches of the sensitive skin-derived mouse to which each cleaning composition was applied.

-Evaluation criteria-
5 points: reduction rate is 60% or more 4 points: reduction rate is 50% or more and less than 60% 3 points: reduction rate is 40% or more and less than 50% 2 points: reduction rate is 30% or more and less than 40% 1 Point: The reduction rate is 10% or more and less than 30% 0 point: The reduction rate is less than 10% In the above evaluation criteria, 3 points or more were regarded as effective.

  From the results of Comparative Examples 14 to 17, when the (C) component and the (D) component are not used in combination (Comparative Examples 14 and 15), the stability at low temperature is poor, and the precipitation of the (B) component is observed and transparent. It was found that a satisfactory liquid appearance could not be obtained, and sufficient suppression effect could not be obtained due to precipitation of component (B). Moreover, when (E) component was not mix | blended (comparative example 17), (A) component could not be mix | blended stably and the liquid external appearance worsened. When the component (B) was not blended, no depressive effect was obtained.

On the other hand, in Examples 56-72, (A) component, (B) component, (C) component, (D) component, and (E) component are contained in the range of this invention, and favorable stability is contained. And it was found that a depressive effect can be obtained.
In addition, it was found that, when each component is blended within the following range, a transparent liquid appearance with excellent stability can be obtained and a good suppression effect can be obtained.
(A) 0.01 mass%-5 mass% are preferable, and 0.05 mass%-2.5 mass% were more preferable.
(B) 0.01 mass%-10 mass% were preferable, and 0.1 mass%-5 mass% were more preferable.
Component (C) is preferably 0.05% by mass to 10% by mass, and more preferably 0.1% by mass to 5% by mass.
The component (D) is preferably 0.01% by mass to 5% by mass, and more preferably 0.1% by mass to 2% by mass.
Furthermore, (C) / (D) = 1-50 were preferable and, as for mass ratio of content of (C) component and content of (D) component, 2-20 were more preferable.
(E) 50 mass%-90 mass% of the component was preferable.

  Specific examples in which the skin cosmetic composition of the present invention is applied to an actual product are shown below. In addition, the skin cosmetic composition of Examples 73-75 was prepared according to the usual method of each dosage form according to each composition. Moreover, about the following Examples 73-75, the result of having performed evaluation similar to the said Examples 56-72 is also shown below.

(Example 73: Antiperspirant roll-on type)
-Composition-
Tocopherol acetate (component (A)) 0.5%
Maltotetraose (component (B)) 1.0%
PPG-6decyltetradeces-12 (EO: 12, PO: 6) (component (C))
2.0%
Dibutyloctyl sebacate (component (D)) 0.5%
Propylene glycol 3.0%
Aluminum chlorohydrate aqueous solution 10.0%
Benzalkonium chloride (10%) 0.5%
Fragrance 0.3%
Ethanol (component (E)) 70.0%
Purified water balance 100.0%
(C) / (D) = 4 (mass ratio)
Stability: ◎
Depressive effect: 4 points

(Example 74: Skin lotion)
-Composition-
Retinol (component (A)) 0.5%
α-Lipoic acid (component (A)) 0.01%
Pentadecanoic acid monoglyceride 2.5%
Maltotetraose (component (B)) 1.0%
PPG-6decyltetradeces-12 (EO: 12, PO: 6) (component (C))
2.0%
Dibutyloctyl sebacate (component (D)) 0.5%
Propylene glycol 3.0%
Octyldodecyl lactate 0.5%
Polyethylene glycol 300 1.0%
L-menthol 0.1%
Fragrance 0.05%
Ethanol (component (E)) 70.0%
Purified water balance 100.0%
(C) / (D) = 4 (mass ratio)
Stability: ◎
Depressive effect: 4 points

(Example 75: Skin lotion)
CoQ10 ((A) component) 0.3%
Maltotetraose (component (B)) 1.0%
PPG-6decyltetradeces-12 (EO: 12, PO: 6) (component (C))
4.0%
Dibutyloctyl sebacate (component (D)) 0.5%
Propylene glycol 3.0%
Nicotinamide 0.1%
L-Menthol 0.5%
Fragrance 0.5%
Ethanol (component (E)) 70.0%
Purified water balance 100.0%
(C) / (D) = 8 (mass ratio)
Stability: ◎
Depressive effect: 4 points

  The raw materials used in Examples 1 to 75 and Comparative Examples 1 to 17 are as shown in Table 13 below.

  The cosmetic composition of the present invention can be used in combination with a maltooligosaccharide and a sparingly water-soluble active ingredient, can be stably stored without precipitating the maltooligosaccharide, and has an inhibitory effect, male pattern baldness and stress. Since it has an excellent hair growth effect against sexual alopecia, it can be applied to skin cosmetics and hair growth compositions such as antiperspirants, skin lotions, hair growth agents, hair growth lotions, hair growth gels, hair growth tonics, hair growth sprays, hair growth tonic sprays, etc. It can be suitably used.

Claims (5)

(A) at least one selected from 6-benzylaminopurine, β-glycyrrhetinic acid, minoxidil, adenosine, pentadecanoic acid monoglyceride, retinol, tocopherol acetate, coenzyme Q10, and α lipoic acid, and (B) maltooligosaccharide, (C) an alkyl ether having polyoxyethylene, and at least one of an alkyl ether having polyoxyethylene and polyoxypropylene, (D) a dibasic acid diester, and (E) ethanol,
The average addition mole number of the ethylene oxide of the alkyl ether having polyoxyethylene in the component (C) is 4 to 15, and the average of the ethylene oxide of the alkyl ether having polyoxyethylene and polyoxypropylene in the component (C) The addition mole number is 4 to 15, and the average addition mole number of propylene oxide is 2 to 6,
Content of said (E) component is 50 mass%-90 mass%
A cosmetic composition characterized by the above. The cosmetic composition according to claim 1, wherein (D) the dibasic acid diester is at least one selected from dibutyloctyl sebacate, diethylhexyl naphthalenedicarboxylate, diethyl sebacate, diisopropyl sebacate, and diisopropyl adipate. object. (C) The mass ratio of the alkyl ether having polyoxyethylene, and the content of at least one of the alkyl ether having polyoxyethylene and polyoxypropylene, and the content of (D) dibasic acid diester,
(C) / (D) = 1-50
The cosmetic composition according to any one of claims 1 to 2. The component (A) is at least one selected from 6-benzylaminopurine, β-glycyrrhetinic acid, minoxidil, adenosine, and pentadecanoic acid monoglyceride, and is used as a hair restorer composition. The cosmetic composition according to 1. The cosmetic composition according to any one of claims 1 to 3, wherein the component (A) is at least one selected from retinol, tocopherol acetate, coenzyme Q10, and alpha lipoic acid, and is used as a skin cosmetic composition. object.