Hair growth agent, FGF-7 production promoting agent, and composition for scalp and hair
The use of ozonated glycerin or cyclic peroxide in a hair growth agent and FGF-7 production promoter addresses the inadequacies of existing products by enhancing hair growth and FGF-7 production, resulting in improved hair thickness and volume, and scalp health.
Patent Information
- Application Number
- PCT/JP2024/021035
- Authority / Receiving Office
- WO · WO
- Patent Type
- Applications
- Current Assignee / Owner
- Priority Date
- 2024-01-31
- Filing Date
- 2024-06-10
- Publication Date
- 2024-12-19
AI Technical Summary
Current hair growth agents and FGF-7 production promoters have insufficient effects on improving hair thickness and volume, and there is a need for a substance with excellent hair-growth and hair-nourishing effects, particularly one that promotes high FGF-7 production.
A hair growth agent and FGF-7 production promoter containing specific ozonated glycerin or cyclic peroxide, with an oxidizing power of 10 ppm to 5,000 ppm, which enhances hair growth and FGF-7 production, formulated into a scalp and hair composition.
The composition effectively promotes hair growth, prevents hair loss, and improves hair thickness and volume by enhancing FGF-7 production, providing a nourishing effect that maintains scalp health and hair growth.
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Figure JP2024021035_19122024_PF_FP_ABST
Abstract
Description
Hair growth agent, FGF-7 production promoter, and composition for scalp and hair Related Applications
[0001] This application claims priority to Japanese Patent Application No. 2023-95963 filed on June 12, 2023, and Japanese Patent Application No. 2024-12554 filed on January 31, 2024, the contents of which are all incorporated herein by reference.
[0002] The present invention relates to a hair care agent, an FGF-7 production promoter, and a composition for scalp and hair.
[0003] Ozone-treated glycerin, which has been given oxidizing ability by ozone treatment, has been known and has been used in applications such as a disinfectant (see, for example, Patent Documents 1 to 3), a tooth whitening agent (see, for example, Patent Document 4), and an inducer of heat shock protein expression (see, for example, Patent Document 5).
[0004] On the other hand, Fibroblast Growth Factor-7 (hereinafter abbreviated as "FGF-7"), a type of cell growth factor, is produced by hair papilla cells, acts on hair matrix cells, and promotes hair growth by stimulating the proliferation and division of hair matrix cells, and it is known that its expression is reduced in areas of thinning hair. In this regard, for example, a method for maintaining and promoting hair thickening by enhancing the expression of FGF-7 in hair follicle cells, and a composition that enhances the expression of FGF-7 containing adenosine or a derivative thereof have been proposed (see, for example, Patent Document 6). However, the proposed adenosine or derivative thereof was insufficient in improving hair thickness and increasing hair volume through hair growth.
[0005] Japanese Patent Publication No. 2003-55107 Japanese Patent No. 4677192 Japanese Patent No. 5222344 Japanese Patent No. 6431251 Japanese Patent No. 6671832 International Publication No. 2005 / 044205
[0006] As described above, ozone-treated glycerin is known to have various effects, but it has not been known until now that a specific ozone-treated glycerin has an excellent hair-growth and / or hair-restoring effect and can be effectively used as a hair-restoring agent, and this is a new finding by the present inventors. Furthermore, there is currently a strong demand for the provision of substances having an excellent hair-restoring and / or hair-restoring effect, as well as substances having high FGF-7 production-promoting activity.
[0007] The present invention aims to solve the above-mentioned problems of the prior art and to achieve the following objects. Specifically, the present invention aims to provide a hair care agent containing a specific ozone-treated glycerin or a specific cyclic peroxide or a salt thereof and having excellent hair care and / or hair growth effects, and a composition for scalp and hair containing the hair care agent. Another object of the present invention is to provide an FGF-7 production promoter containing a specific ozone-treated glycerin or a specific cyclic peroxide or a salt thereof and having high FGF-7 production-promoting activity, and a composition for scalp and hair containing the FGF-7 production promoter.
[0008] The hair care and growth agent of the present invention, which is a means for solving the above problems, contains ozone-treated glycerin having an oxidizing power of 10 ppm to 5,000 ppm in terms of ozone concentration. The hair care and growth agent of the present invention also contains a cyclic peroxide or a salt thereof represented by the following chemical formula (1):
[0009] The FGF-7 production enhancer of the present invention comprises ozone-treated glycerin having an oxidizing power of 10 ppm to 5,000 ppm in terms of ozone concentration. The FGF-7 production enhancer of the present invention also comprises a cyclic peroxide represented by the following chemical formula (1) or a salt thereof:
[0010] Furthermore, the composition for scalp and hair of the present invention contains the hair care agent or the FGF-7 production promoter of the present invention.
[0011] According to the present invention, the above-mentioned problems of the prior art can be solved and the above-mentioned objects can be achieved, and it is possible to provide a hair care agent containing a specific ozone-treated glycerin, or a specific cyclic peroxide or a salt thereof, and having excellent hair care and / or hair growth effects, and a composition for scalp and hair containing the hair care agent. Another object of the present invention is to provide an FGF-7 production promoter containing a specific ozone-treated glycerin, or a specific cyclic peroxide or a salt thereof, and having high FGF-7 production-promoting activity, and a composition for scalp and hair containing the FGF-7 production promoter.
[0012] FIG. 1 shows the DMSO-d 6 was used as a solvent and measured at a temperature of 300 K (27 °C). 1 1 H NMR spectrum of the reaction mixture (TLC 1 spot) of glycerin ozone oxidation. 6 was used as a solvent and measured at a temperature of 300 K (27 °C). 13 3 shows the C NMR spectrum of the reaction mixture (TLC 1 spot) of glycerin ozone oxidation in DMSO-d 6 was used as a solvent and measured at a temperature of 300 K (27 °C). 13 4 shows the C DEPT135 NMR spectrum of the reaction mixture (TLC 1 spot) of glycerin ozone oxidation. 6 As a solvent, the COSY NMR spectrum was measured at a temperature of 300 K (27° C.). 6 6 shows the HSQC NMR spectrum measured at a temperature of 300 K (27° C.) using DMSO-d 6FIG. 7 shows the HMBC NMR spectrum measured at 300 K (27°C) using acetonitrile as a solvent. FIG. 7 shows the total ion chromatogram (ESI-negative mode) of the precision preparative LC (liquid chromatography) of a sample prepared by diluting the reaction mixture (TLC 1 spot) with acetonitrile to approximately 3% by mass, and a blank. FIG. 8 shows the mass spectrum of peaks F, G, and H (Fraction F, Fraction G, and Fraction H) in FIG. 7. FIG. 9 shows the results of an investigation into improved separation (improved separation conditions) in HILIC (high-performance liquid chromatography). FIG. 10 shows the mass spectrum of peaks 1 to 3 in FIG. 9 (after improved separation). FIG. 11 shows the mass spectrum of peaks 4 to 6 in FIG. 9 (after improved separation). FIG. 12 shows the mass spectrum of peaks 7 and 8 in FIG. 9 (after improved separation). Fig. 13 shows the microscopic Raman spectrum of a sample of peak 2 (Mw = 180) in Fig. 9 and that of an ozonide standard. 1 15 is a H NMR spectrum of peak 2 (Mw=180) in FIG. 13 16 shows the two-dimensional ( 1 H- 131C COSY NMR spectrum. FIG. 17 shows the HILIC chromatograms of the TLC1 spot product and glyceraldehyde dimer under the HILIC (high performance liquid chromatography) conditions of FIG. 9 together. FIG. 18 shows the HILIC chromatograms of the TLC1 spot product and glyceraldehyde dimer under reversed-phase HILIC (high performance liquid chromatography) conditions together. FIG. 19 is an enlarged view of a portion of FIG. 18. FIG. 20 shows the ESR spectrum of the TLC1 spot product and peak 2 (Mw = 180) in FIG. 7 together. FIG. 21 shows the ESR spectrum of ozonated methyl linolenate. FIG. 22 shows the ESR spectrum of peaks 1 to 8 in FIG. 9. FIG. 23 shows the results of measuring the activity of peaks 1 to 8 in FIG. 9 by chemiluminescence. FIG. 24 shows microscope photographs of the scalp condition before starting use of Sample R and after 12 weeks of application of Sample R. Figure 25 is a photograph taken with a microscope of the condition of the scalp before starting to use sample D and 12 weeks after applying sample D. Figure 26 is a photograph taken with a microscope of the condition of the scalp before starting to use sample C and 12 weeks after applying sample C.
[0013] (Hair Growth Agent) In a first embodiment, the hair growth agent of the present invention contains a specific ozone-treated glycerin and, if necessary, further contains other ingredients. In a second embodiment, the hair growth agent of the present invention contains a cyclic peroxide represented by the following chemical formula (1) or a salt thereof and, if necessary, further contains other ingredients.
[0014]
[0015] As a result of extensive research into substances having hair growth and / or hair care effects, the present inventors unexpectedly discovered that a specific ozone-treated glycerin or a cyclic peroxide represented by the above chemical formula (1) or a salt thereof has excellent hair care and / or hair care effects, and found that a scalp and hair composition containing this specific ozone-treated glycerin or a cyclic peroxide represented by the above chemical formula (1) or a salt thereof can be effectively used in the fields of cosmetics, pharmaceuticals, quasi-drugs, etc., thereby completing the present invention. Furthermore, the cyclic peroxide represented by the above chemical formula (1) is chemically stable and easy to handle compared to, for example, radicals, and therefore can be isolated and formulated.
[0016] In the present invention, the hair-growth effect refers to the effect of suppressing dandruff and itching, replenishing moisture, oil, etc. that tend to be lacking, and maintaining the health of hair and scalp. The hair-growth effect refers to the effect of keeping the scalp clean and creating an environment conducive to hair growth. It also refers to the effect of preventing further hair loss by preventing the production of substances that cause hair thinning, that is, the effect of preventing hair loss, the effect of preventing hair loss, and the effect of promoting hair growth.
[0017] <Specific ozone-treated glycerin> The specific ozone-treated glycerin in the hair care agent has an oxidizing power, calculated as an ozone concentration, of 10 ppm or more, and can be 30 ppm or more, 50 ppm or more, 100 ppm or more, or 200 ppm or more. The specific ozone-treated glycerin in the hair care agent has an oxidizing power, calculated as an ozone concentration, of 5,000 ppm or less, and can be 2,000 ppm or less, 1,000 ppm or less, 500 ppm or less, or 200 ppm or less. When the oxidizing power, calculated as an ozone concentration, is within the above range, excellent hair care and / or hair growth effects can be achieved. The oxidizing power, calculated as an ozone concentration, of the ozone-treated glycerin can be measured, for example, by potassium iodide titration.
[0018] The specific ozone-treated glycerin is not particularly limited as long as it satisfies the above-mentioned range of oxidizing power converted into ozone concentration and has a hair-growth effect, and can be appropriately selected depending on the purpose.
[0019] The ozone-treated glycerin is obtained by gas-liquid contact of a glycerin solution with a gas containing ozone. The glycerin concentration in the glycerin solution is not particularly limited and can be appropriately selected depending on the purpose, but a glycerin concentration of 10% by mass or more is preferred, more preferably 50% by mass or more, and even more preferably 80% by mass or more. Specifically, a glycerin solution of 84% by mass or more as specified in the Japanese Pharmacopoeia is preferred, a concentrated glycerin solution of 98% by mass or more as specified in the Japanese Pharmacopoeia is more preferred, and a purified glycerin solution of 98.5% by mass or more as specified in the Japanese Pharmacopoeia is even more preferred. The solvent for glycerin in the glycerin solution is not particularly limited and may be, for example, an aqueous solvent such as water.
[0020] The ozone-containing gas preferably has a high ozone concentration. The method for producing the gas with a high ozone concentration is not particularly limited, and for example, a silent discharge ozone generator that generates ozone by silently discharging oxygen gas can be used. When oxygen gas is used, for example, a medical oxygen cylinder can be used, or oxygen produced by an oxygen generator can be used.
[0021] The method for bringing the glycerin solution into gas-liquid contact with the ozone-containing gas is not particularly limited, and for example, there is a method in which the glycerin solution is placed in a tank and the gas with a high ozone concentration is released into the tank as fine bubbles using an air diffuser. Specifically, by aerating a gas with an ozone concentration of about 37,000 ppm into the concentrated glycerin solution for a predetermined period of time, ozone-treated glycerin having an oxidizing power of 10 ppm to 5,000 ppm in terms of ozone concentration can be produced.
[0022] The predetermined aeration time is not particularly limited, and may be, for example, 1 hour or more, 5 hours or more, 10 hours or more, 15 hours or more, 24 hours or more or 1 day or more, 48 hours or more or 2 days or more, 72 hours or more or 3 days or more, 120 hours or more or 5 days or more, or 168 hours or more or 7 days or more. The upper limit of the predetermined aeration time is not particularly limited, and may be, for example, 720 hours or less or 30 days or less, 360 hours or less or 15 days or less, or 240 hours or less or 10 days or less.
[0023] The ozone-treated glycerin may be a low-oxidizing ozone-treated glycerin having an oxidizing power of 200 ppm or less, which is obtained by diluting a high-oxidizing ozone-treated glycerin having an oxidizing power of 2,000 ppm or more with an untreated glycerin solution. The glycerin concentration in the untreated glycerin solution is not particularly limited and can be appropriately selected depending on the purpose. For example, the glycerin concentration is preferably 10% by mass or more, more preferably 50% by mass or more, and even more preferably 80% by mass or more.
[0024] The obtained specific ozone-treated glycerin can be used as a hair care agent as it is, but it is preferable that it further contains other components as necessary. The content of the specific ozone-treated glycerin in the hair care agent is not particularly limited and can be adjusted appropriately. The hair care agent may consist only of the specific ozone-treated glycerin.
[0025] <Cyclic peroxide represented by chemical formula (1) or salt thereof> The cyclic peroxide represented by the following chemical formula (1) contained in the hair care agent of the second embodiment of the present invention is a cyclic peroxide represented by the following chemical formula (I) in which R 11 is the case where all atoms are hydrogen atoms.
[0026]
[0027] In the chemical formula (I), each R 11 may be the same or different and each represents a hydrogen atom, a hydroxyl group, a hydroxyalkyl group, or an alkyl group. The number of carbon atoms in the hydroxyalkyl group or alkyl group is preferably 1 to 10, more preferably 1 to 5, and even more preferably 1 to 3. Examples of the alkyl group include a methyl group, an ethyl group, and a propyl group.
[0028] When the cyclic peroxide represented by the above chemical formula (1) can form a salt, the salt may be an acid addition salt or a base addition salt. Furthermore, the acid that forms the acid addition salt may be an inorganic acid or an organic acid, and the base that forms the base addition salt may be an inorganic base or an organic base. Examples of inorganic acids include, but are not limited to, sulfuric acid, phosphoric acid, hydrofluoric acid, hydrochloric acid, hydrobromic acid, hydroiodic acid, hypofluorite acid, hypochlorous acid, hypobromous acid, hypoiodous acid, fluorite acid, chlorous acid, bromous acid, iodous acid, fluoric acid, chloric acid, bromic acid, iodic acid, perfluoric acid, perchloric acid, perbromic acid, and periodic acid. Examples of organic acids include, but are not limited to, p-toluenesulfonic acid, methanesulfonic acid, oxalic acid, p-bromobenzenesulfonic acid, carbonic acid, succinic acid, citric acid, benzoic acid, and acetic acid. The inorganic base is not particularly limited, but examples thereof include ammonium hydroxide, alkali metal hydroxides, alkaline earth metal hydroxides, carbonates, and hydrogen carbonates, and more specific examples thereof include sodium hydroxide, potassium hydroxide, potassium carbonate, sodium carbonate, sodium hydrogen carbonate, potassium hydrogen carbonate, calcium hydroxide, and calcium carbonate. The organic base is not particularly limited, but examples thereof include ethanolamine, triethylamine, and tris(hydroxymethyl)aminomethane. The method for producing these salts is also not particularly limited, and they can be produced, for example, by a method in which the above-mentioned acid or base is appropriately added to the compound by a known method.
[0029] The method for producing the cyclic peroxide represented by the above chemical formula (1) is not particularly limited, but it can be produced by oxidizing an alcohol. In this case, for example, the produced cyclic peroxide represented by the above chemical formula (1) may be used as is without purification, or only the cyclic peroxide represented by the above chemical formula (1) may be isolated and purified and used. The present inventors were the first to discover the phenomenon that cyclic peroxides can be obtained by the oxidation of alcohols, for example, the ozone oxidation of glycerin. The mechanism by which cyclic peroxides are obtained is unknown, but it is speculated that a reaction product different from conventional reactions can be obtained, for example, by extending the reaction time of the alcohol oxidation reaction, as described below.
[0030] The method for oxidizing the alcohol is not particularly limited. For example, the oxidation of the alcohol may be at least one of ozone oxidation and hydrogen peroxide oxidation. However, the method for oxidizing the alcohol is not limited to ozone oxidation and hydrogen peroxide oxidation of the alcohol, and any production method may be used as long as the substance has the same structure.
[0031] The alcohol used as a raw material is not particularly limited and may be, for example, a saturated alcohol or an unsaturated alcohol. The alcohol may be linear or branched, and may or may not contain a cyclic structure. The alcohol may be, for example, a polyhydric alcohol or a monohydric alcohol. The valence of the polyhydric alcohol is also not particularly limited and may be, for example, dihydric, trihydric, or tetrahydric. Examples of monohydric saturated alcohols include saturated alcohols having 1 to 40, 1 to 32, 1 to 24, 1 to 18, 1 to 12, 1 to 6, or 1 to 2 carbon atoms. The saturated alcohol may be linear or branched and may or may not contain a cyclic structure. Examples include methanol, ethanol, n-propyl alcohol, isopropyl alcohol, n-butyl alcohol, sec-butyl alcohol, and tert-butyl alcohol. Examples of saturated polyhydric alcohols include saturated polyhydric alcohols having 1 to 40, 1 to 32, 1 to 24, 1 to 18, 1 to 12, 1 to 6, or 1 to 2 carbon atoms. The saturated polyhydric alcohols may be linear or branched, and may or may not contain a cyclic structure. Examples include ethylene glycol (ethane-1,2-diol), propylene glycol (propane-1,2-diol), glycerin, and glycerin derivatives. The glycerin derivatives are not particularly limited, and may be, for example, glycerin polymers or compounds in which at least one hydrogen atom of glycerin is substituted with a substituent (e.g., an alkyl group). Examples of glycerin derivatives include diglycerin and polyglycerin.
[0032] The reaction time of the alcohol oxidation step is not particularly limited. The reaction time of the alcohol oxidation step may be, for example, 1 hour or more, 5 hours or more, 10 hours or more, 15 hours or more, 24 hours or more, or 1 day or more, 48 hours or more, or 2 days or more, 72 hours or more, or 3 days or more, 120 hours or more, or 5 days or more, or 168 hours or more, or 7 days or more. The upper limit of the predetermined aeration time is not particularly limited, and may be, for example, 720 hours or less, 30 days or less, 360 hours or less, 15 days or less, or 240 hours or less, or 10 days or less.
[0033] In order to obtain the cyclic peroxide represented by the above chemical formula (1), it is preferable to extend the reaction time of the alcohol oxidation step. For example, by extending the reaction time of the alcohol oxidation step, it is possible to produce the cyclic peroxide represented by the above chemical formula (1), which could not be obtained by conventional ozone oxidation reactions of glycerin, etc. In addition, for the sake of production efficiency, it is preferable that the reaction time of the alcohol oxidation step is not too long.
[0034] As described above, the method for producing the cyclic peroxide represented by the chemical formula (1) includes an alcohol oxidation step of oxidizing the alcohol. However, the cyclic peroxide represented by the chemical formula (1) is not limited to a substance produced by this method, and may be a substance produced by any method as long as it has the same structure.
[0035] The following description will be given taking as an example a case where glycerin is used as the alcohol and oxidation with ozone. However, as mentioned above, the following description is merely an example, and the method for producing the cyclic peroxide represented by the above chemical formula (1) is not limited to the following description. For example, the following method can be carried out in the same manner using other alcohols instead of glycerin. For example, in the method for producing the cyclic peroxide represented by the above chemical formula (1), the method for oxidizing the alcohol is not particularly limited and is arbitrary, and is not limited to ozone oxidation. The oxidation method may be, for example, at least one of ozone oxidation and hydrogen peroxide oxidation. Furthermore, for example, not only the type of alcohol and the method for oxidizing the alcohol, but also the concentration of each substance, reaction temperature, reaction time, and other reaction conditions can be changed as appropriate.
[0036] The glycerin solution preferably has a high glycerin concentration. Examples of the high-concentration glycerin solution include a glycerin solution having a glycerin concentration of 75% or more. Specific examples include a glycerin solution having a glycerin concentration of 84 to 87% by weight as specified in the Japanese Pharmacopoeia, a concentrated glycerin solution having a glycerin concentration of 98% by weight or more as specified in the Japanese Pharmacopoeia, and a purified glycerin solution having a concentration of 98.5% by weight or more. For example, the glycerin solution can be treated with ozone at a higher concentration as the glycerin concentration is relatively higher. The solvent for glycerin in the glycerin solution is not particularly limited and may be, for example, an aqueous solvent such as water.
[0037] The ozone-containing gas preferably has a high ozone concentration. The method for producing the gas with a high ozone concentration is not particularly limited, and for example, an ozone generator that generates ozone by silently discharging oxygen gas can be used. When oxygen gas is used, for example, a medical oxygen cylinder can be used, or oxygen gas produced by an oxygen generator can be used.
[0038] The method for bringing the glycerin solution into gas-liquid contact with the ozone-containing gas is not particularly limited, and for example, a method is available in which a high-concentration (e.g., 98% by weight or more) glycerin solution is placed in a tank and the high-ozone-concentration gas is released into the tank as fine bubbles using an air diffuser. Specifically, for example, an ozone-treated glycerin solution having an equivalent hydrogen peroxide concentration of about 4000 ppm can be produced by aerating a gas having an ozone concentration of about 37,000 ppm into the concentrated glycerin solution for about 7 days. The aeration time is not particularly limited, and for example, an ozone-treated glycerin solution containing a higher concentration of the cyclic peroxide represented by the above chemical formula (1) can be produced by aerating the concentrated glycerin solution for a relatively longer period of time.
[0039] The cyclic peroxide represented by the chemical formula (1) may be used as is without being separated from the reaction mixture (e.g., the ozone-treated glycerin solution), or may be used after being separated from the reaction mixture. The separation method is not particularly limited, and the cyclic peroxide represented by the chemical formula (1) can be separated from the reaction mixture by chromatography such as preparative thin-layer chromatography, for example.
[0040] Conventionally, the production of substances such as peroxides having oxidizing power required a complex system. However, the method for producing the cyclic peroxide represented by the above chemical formula (1) makes it possible to produce, for example, an oxidation reaction product having oxidizing power in an extremely simple and easy manner.
[0041] <Other Components> The other components are not particularly limited and can be appropriately selected depending on the form of use of the hair care agent, and examples thereof include hair care aids, preservatives, strengthening agents, thickeners, emulsifiers, antioxidants, colorants, powder components, aqueous components, water, etc. These may be used alone or in combination of two or more.
[0042] -Hair-Growth Aid- The hair-growth aid is not particularly limited as long as it is a component that enhances hair-growth and / or hair-restoring effects, and can be appropriately selected depending on the purpose. Examples include Swertia japonica extract, Sargassum serrata extract, Red clover flower extract, pyrrolidinyldiaminopyrimidine oxide, acetyl tetrapeptide-3, pyridoxine hydrochloride, tocopherol acetate, diphenhydramine hydrochloride, thiosulfate, pentadecanoic acid glyceride, 6-benzylaminopurine, hinokitiol, minoxidil, carpronium chloride, t-flavanone, piroctone olamine, β-glycyrrhetinic acid, isopropylmethylphenol, forskolin, sweltiamarin, and adenosine. These may be used alone or in combination of two or more. Among these, Swertia japonica extract and pyrrolidinyldiaminopyrimidine oxide are preferred. The content of the hair-growth aid in the hair-growth agent is not particularly limited and can be adjusted appropriately.
[0043] (FGF-7 production promoter) In a first embodiment, the FGF-7 production promoter of the present invention contains a specific ozone-treated glycerin and, if necessary, further contains other components. In a second embodiment, the FGF-7 production promoter of the present invention contains a cyclic peroxide represented by the following chemical formula (1) or a salt thereof and, if necessary, further contains other components.
[0044]
[0045] As a result of extensive research into substances that have the effect of promoting FGF-7 production, the present inventors unexpectedly found that a specific ozone-treated glycerin or a cyclic peroxide represented by the above chemical formula (1) or a salt thereof has a high FGF-7 production promoting effect, and discovered that a composition for scalp and hair containing this specific ozone-treated glycerin or a cyclic peroxide represented by the above chemical formula (1) or a salt thereof can be effectively used in the fields of cosmetics, pharmaceuticals, quasi-drugs, etc., thereby completing the present invention. Furthermore, the cyclic peroxide represented by the above chemical formula (1) is chemically stable and easy to handle compared to, for example, radicals, and therefore can be isolated and formulated into pharmaceutical preparations.
[0046] Hair grows and falls out repeatedly according to a cyclical hair cycle (hair cycle) consisting of an anagen phase, a regressive phase, and a telogen phase. The stage of this hair cycle, during which new hair follicles are formed from the telogen phase to the anagen phase, is considered to be the most important for hair growth, and dermal papilla cells are thought to play an important role in the proliferation and differentiation of hair follicle epithelial cells during this stage. Dermal papilla cells are located inside hair follicle epithelial cells, which are composed of outer root sheath cells and matrix cells near the hair root, in the basement membrane-enclosed shaft portion of the hair root. They act on hair follicle epithelial cells to promote their proliferation, and thus play an important role in the proliferation and differentiation of hair follicle epithelial cells and hair formation (see J. Derm. Sci., 3, pp. 43-49, 2002).
[0047] Fibroblast growth factor-7 (FGF-7) is a member of the fibroblast growth factor (FGF) family and is also known as KGF (keratinocyte growth factor). It is known that there are more than 20 types of FGF-7 family members. FGF-7 is a factor that promotes the proliferation of a wide range of cells developed from the mesoderm and neuroectoderm, and induces the division and growth of, for example, fibroblasts, vascular endothelial cells, myoblasts, chondrocytes, glial cells, osteoblasts, and the like. FGF-7 is known to have angiogenic effects, inhibitory effects on collagen and fibronectin synthesis, and a strong affinity for heparin. With regard to hair growth, it is believed that FGF-7 is produced by dermal papilla cells, acts on hair matrix cells, and promotes hair growth by stimulating the proliferation and division of hair matrix cells. It has also been shown that FGF-7 is expressed in dermal papilla cells of hair follicles (see, for example, Anti-Aging Series (1), The Truth About Gray Hair, Hair Loss, and Hair Growth, NTS, pages 1-18, 2005), revealing that FGF-7 has a hair growth effect through activation of hair roots. Furthermore, research using knockout mice suggests that FGF-7 is involved in the direction of hair growth. Furthermore, promotion of FGF-7 production is expected to improve hair thickness and volume, and thus have the effect of rejuvenating the facial impression.
[0048] <Specific Ozone-Treated Glycerin> The specific ozone-treated glycerin in the FGF-7 production promoter has an oxidizing power, calculated as an ozone concentration, of 0.02 ppm or more, and can be 0.03 ppm or more, 0.05 ppm or more, 0.1 ppm or more, 0.5 ppm or more, 1 ppm or more, 5 ppm or more, or 10 ppm or more. Furthermore, the specific ozone-treated glycerin in the FGF-7 production promoter has an oxidizing power, calculated as an ozone concentration, of 5,000 ppm or less, and can be 2,000 ppm or less, 1,000 ppm or less, 500 ppm or less, 200 ppm or less, 100 ppm or less, 50 ppm or less, or 10 ppm or less. When the oxidizing power, calculated as an ozone concentration, is within the above range, an excellent FGF-7 production-promoting effect can be achieved. The specific ozone-treated glycerin in the FGF-7 production promoter is the same as the specific ozone-treated glycerin in the hair care agent, except for the above-mentioned numerical range of oxidizing power, and therefore a description thereof will be omitted.
[0049] <Cyclic peroxide represented by chemical formula (1) or salt thereof> The cyclic peroxide represented by chemical formula (1) or salt thereof of the FGF-7 production promoter is the same as the cyclic peroxide represented by chemical formula (1) or salt thereof of the above-mentioned hair care and growth agent, and therefore description thereof will be omitted.
[0050] <Other Components> The other components in the FGF-7 production promoter are the same as the other components in the above-mentioned hair care and growth agent, and therefore, description thereof will be omitted.
[0051] The hair care and growth agent or the FGF-7 production promoter of the present invention has high fibroblast growth factor-7 (FGF-7) production-promoting activity and excellent hair care and / or hair growth effects, and can be suitably used in the composition for scalp and hair of the present invention described below.
[0052] (Composition for Scalp and Hair) The composition for scalp and hair of the present invention contains the hair care agent or the FGF-7 production promoter of the present invention, and preferably contains a hair care auxiliary, and further contains other ingredients as necessary.
[0053] <Hair growth agent or FGF-7 production promoter> The hair growth agent or FGF-7 production promoter used is the hair growth agent or FGF-7 production promoter of the present invention described above. The content of the hair growth agent or FGF-7 production promoter is not particularly limited and can be selected as appropriate, but is preferably 0.01 mg / g or more, more preferably 0.1 mg / g or more, even more preferably 1 mg / g or more, particularly preferably 5 mg / g or more, and even more particularly preferably 10 mg / g or more, of the composition for scalp and hair.
[0054] <Hair-growth aid> As the hair-growth aid, the hair-growth aid in the hair-growth agent of the present invention described above is used.
[0055] <Other Components> Examples of the other components include water, anionic surfactants, cationic surfactants, amphoteric surfactants, nonionic surfactants, moisturizers, water-soluble polymers, thickeners, film-forming agents, ultraviolet absorbers, sequestering agents, lower alcohols, polyhydric alcohols, oils, sugars, amino acids, organic amines, polymer emulsions, pH adjusters, skin nutrients, vitamins, plant extracts, antioxidants, antioxidant aids, fragrances, colorants, preservatives, and disinfectants.
[0056] Examples of water include purified water, distilled water, ion-exchanged water, pure water, ultrapure water, and deep sea water.
[0057] Examples of cationic surfactants include alkyltrimethylammonium salts (e.g., stearyltrimethylammonium chloride, behenyltrimethylammonium chloride, etc.); alkylpyridinium salts (e.g., cetylpyridinium chloride, etc.); distearyldimethylammonium chloride, dialkyldimethylammonium salts; poly(N,N'-dimethyl-3,5-methylenepiperidinium) chloride; alkyl quaternary ammonium salts; alkyldimethylbenzylammonium salts; alkylisoquinolinium salts; dialkylmorphonium salts; POE-alkylamines; alkylamine salts; polyamine fatty acid derivatives; amyl alcohol fatty acid derivatives; benzalkonium chloride; benzethonium chloride, etc. These may be used alone or in combination of two or more.
[0058] Examples of amphoteric surfactants include imidazoline-based amphoteric surfactants (e.g., 2-undecyl-N,N,N-(hydroxyethylcarboxymethyl)-2-imidazoline sodium, 2-cocoyl-2-imidazolinium hydroxide-1-carboxyethyloxy disodium salt, 2-heptadecyl-N-carboxymethyl-N-hydroxyethylimidazolinium betaine, etc.); betaine-based surfactants (e.g., lauryldimethylaminoacetic acid betaine, alkyl betaine, alkylamido betaine, alkyl sulfobetaine, etc.). These may be used alone or in combination of two or more.
[0059] Examples of lipophilic nonionic surfactants include sorbitan fatty acid esters (e.g., sorbitan monooleate, sorbitan monoisostearate, sorbitan monolaurate, sorbitan monopalmitate, sorbitan monostearate, sorbitan sesquioleate, sorbitan trioleate, diglycerol sorbitan penta-2-ethylhexylate, diglycerol sorbitan tetra-2-ethylhexylate, etc.); glycerin polyglycerin fatty acids (e.g., glycerin monocottonseed oil fatty acid, glycerin monoerucate, glycerin sesquioleate, glycerin monostearate, glycerin α,α'-oleic acid pyroglutamate, glycerin monostearate malate, etc.); propylene glycol fatty acid esters (e.g., propylene glycol monostearate, etc.); hydrogenated castor oil derivatives; glycerin alkyl ethers, etc. These may be used alone or in combination of two or more.
[0060] Examples of hydrophilic nonionic surfactants include POE-sorbitan fatty acid esters (e.g., POE-sorbitan monooleate, POE-sorbitan monostearate, POE-sorbitan monooleate, POE-sorbitan tetraoleate, etc.); POE-sorbitol fatty acid esters (e.g., POE-sorbitol monolaurate, POE-sorbitol monooleate, POE-sorbitol pentaoleate, POE-sorbitol monostearate, etc.); POE-glycerin fatty acid esters (e.g., POE-glycerin monostearate, POE-monooleates such as POE-glycerin monoisostearate, POE-glycerin triisostearate, etc.); POE-fatty acid esters (for example, POE-distearate, POE-monodioleate, ethylene glycol distearate, etc.); POE-alkyl ethers (for example, POE-lauryl ether, POE-oleyl ether, POE-stearyl ether, POE-behenyl ether, POE-2-octyldodecyl ether, POE-cholestanol ether, etc.); Pluronic (registered trademark) products; POE POP- Alkyl ethers (e.g., POE·POP-cetyl ether, POE·POP-2-decyltetradecyl ether, POE·POP-monobutyl ether, POE·POP-hydrogenated lanolin, POE·POP-glycerin ether, etc.); tetraPOE·tetraPOP-ethylenediamine condensates (e.g., Tetronic, etc.); POE-castor oil hydrogenated castor oil derivatives (e.g., POE-castor oil, POE-hydrogenated castor oil, POE-hydrogenated castor oil monoisostearate, POE-hydrogenated castor oil triisostearate, POE-hydrogenated castor oil monopyrogulol, etc.); tamic acid monoisostearate diester, POE-hydrogenated castor oil maleic acid, etc.); POE-beeswax / lanolin derivatives (for example, POE-sorbitol beeswax, etc.); alkanolamides (for example, coconut oil fatty acid diethanolamide, lauric acid monoethanolamide, fatty acid isopropanolamide, cocamide methyl monoethanolamide, etc.); POE-propylene glycol fatty acid esters; POE-alkylamines; POE-fatty acid amides; diethylene glycol laurate; sucrose fatty acid esters; alkylethoxydimethylamine oxide;trioleyl phosphate, etc. These may be used alone or in combination of two or more.
[0061] Examples of moisturizing agents include glycerin, sugar alcohols, polyethylene glycol, propylene glycol, dipropylene glycol, 1,3-butylene glycol, chondroitin sulfate, hyaluronic acid, mucoitin sulfate, caronic acid, atelocollagen, cholesteryl-12-hydroxystearate, sodium lactate, bile salts, dl-pyrrolidone carboxylate, alkylene oxide derivatives, short-chain soluble collagen, diglycerin (EO)PO adduct, Rosa robur extract, Achillea millefolium extract, Melilot extract, etc. These may be used alone or in combination of two or more.
[0062] Examples of natural water-soluble polymers include plant-derived polymers (e.g., gum arabic, tragacanth gum, galactan, guar gum, carob gum, karaya gum, carrageenan, pectin, agar, quince seed (marmelo), algae colloid (cassowia extract), starch (rice, corn, potato, wheat), glycyrrhizic acid); microbial-derived polymers (e.g., xanthan gum, dextran, succinoglucan, pullulan, etc.); and animal-derived polymers (e.g., collagen, casein, albumin, gelatin, etc.). These may be used alone or in combination of two or more.
[0063] Examples of semi-synthetic water-soluble polymers include starch-based polymers (e.g., carboxymethyl starch, methylhydroxypropyl starch, etc.); cellulose-based polymers (methyl cellulose, ethyl cellulose, methylhydroxypropyl cellulose, hydroxyethyl cellulose, sodium cellulose sulfate, hydroxypropyl cellulose, carboxymethyl cellulose, sodium carboxymethyl cellulose, crystalline cellulose, cellulose powder, etc.); alginic acid-based polymers (e.g., sodium alginate, propylene glycol alginate, etc.); etc. These may be used alone or in combination of two or more.
[0064] Examples of synthetic water-soluble polymers include vinyl polymers (e.g., polyvinyl alcohol, polyvinyl methyl ether, polyvinylpyrrolidone, carboxyvinyl polymer, etc.); polyoxyethylene polymers (e.g., polyethylene glycol 20,000, 40,000, 60,0000 polyoxyethylene polyoxypropylene copolymers, highly polymerized polyethylene glycol, etc.); acrylic polymers (e.g., sodium polyacrylate, polyethyl acrylate, polyacrylamide, etc.); polyethyleneimine; cationic polymers, etc. These may be used alone or in combination of two or more.
[0065] Examples of thickeners include gum arabic, carrageenan, karaya gum, tragacanth gum, carob gum, quince seed (marmelo), casein, dextrin, gelatin, sodium pectinate, sodium alginate, methylcellulose, ethylcellulose, CMC, hydroxyethylcellulose, hydroxypropylcellulose, PVA, PVM, PVP, sodium polyacrylate, carboxyvinyl polymer, locust bean gum, guar gum, tamarind gum, dialkyldimethylammonium cellulose sulfate, xanthan gum, magnesium aluminum silicate, bentonite, hectorite, magnesium silicate A1 (veegum), laponite, anhydrous silicic acid, etc. These may be used alone or in combination of two or more.
[0066] Examples of the ultraviolet absorber include benzoic acid-based ultraviolet absorbers (e.g., para-aminobenzoic acid (hereinafter abbreviated as PABA), PABA monoglycerin ester, N,N-dipropoxy PABA ethyl ester, N,N-diethoxy PABA ethyl ester, N,N-dimethyl PABA ethyl ester, N,N-dimethyl PABA butyl ester, N,N-dimethyl PABA ethyl ester, etc.); anthranilic acid-based ultraviolet absorbers (e.g., homomenthyl-N-acetylanthranilate, etc.); salicylic acid-based ultraviolet absorbers (e.g., amyl salicylate, , menthyl salicylate, homomenthyl salicylate, octyl salicylate, phenyl salicylate, benzyl salicylate, p-isopropanol phenyl salicylate, etc.); cinnamic acid-based ultraviolet absorbers (e.g., octyl methoxycinnamate, ethyl-4-isopropyl cinnamate, methyl-2,5-diisopropyl cinnamate, ethyl-2,4-diisopropyl cinnamate, methyl-2,4-diisopropyl cinnamate, propyl-p-methoxycinnamate, isopropyl-p-methoxycinnamate, isoamyl-p-methoxycinnamate, ethoxycinnamate, octyl-p-methoxycinnamate (2-ethylhexyl-p-methoxycinnamate), 2-ethoxyethyl-p-methoxycinnamate, cyclohexyl-p-methoxycinnamate, ethyl-α-cyano-β-phenylcinnamate, 2-ethylhexyl-α-cyano-β-phenylcinnamate, glyceryl mono-2-ethylhexanoyl-di-paramethoxycinnamate, etc.); benzophenone-based ultraviolet absorbers (for example, 2,4-dihydroxybenzophenone, 2,2'-dihydroxy-4-methoxybenzophenone, benzophenone, 2,2'-dihydroxy-4,4'-dimethoxybenzophenone, 2,2',4,4'-tetrahydroxybenzophenone, 2-hydroxy-4-methoxybenzophenone, 2-hydroxy-4-methoxy-4'-methylbenzophenone, 2-hydroxy-4-methoxybenzophenone-5-sulfonate, 4-phenylbenzophenone, 2-ethylhexyl-4'-phenyl-benzophenone-2-carboxylate, 2-hydroxy-4-n-octoxybenzophenone, 4-hydroxy-3-carboxybenzophenone, etc.);3-(4'-methylbenzylidene)-d,l-camphor, 3-benzylidene-d,l-camphor; 2-phenyl-5-methylbenzoxazole; 2,2'-hydroxy-5-methylphenylbenzotriazole; 2-(2'-hydroxy-5'-t-octylphenyl) Examples of such compounds include benzotriazole; 2-(2'-hydroxy-5'-methylphenylbenzotriazole; dibenzalazine; dianisoylmethane; 4-methoxy-4'-t-butyldibenzoylmethane; 5-(3,3-dimethyl-2-norbornylidene)-3-pentan-2-one, dimorpholinopyridazino; 2-ethylhexyl-2-cyano-3,3-diphenylacrylate; and 2,4-bis-{[4-(2-ethylhexyloxy)-2-hydroxy]-phenyl}-6-(4-methoxyphenyl)-(1,3,5)-triazine. These compounds may be used alone or in combination of two or more.
[0067] Examples of sequestering agents include 1-hydroxyethane-1,1-diphosphonic acid, 1-hydroxyethane-1,1-diphosphonic acid tetrasodium salt, disodium edetate, trisodium edetate, tetrasodium edetate, sodium citrate, sodium polyphosphate, sodium metaphosphate, gluconic acid, phosphoric acid, citric acid, ascorbic acid, succinic acid, edetic acid, trisodium ethylenediaminehydroxyethyltriacetate, etc. These may be used alone or in combination of two or more.
[0068] Examples of lower alcohols include ethanol, propanol, isopropanol, isobutyl alcohol, t-butyl alcohol, etc. These may be used alone or in combination of two or more.
[0069] Examples of polyhydric alcohols include dihydric alcohols (e.g., ethylene glycol, propylene glycol, trimethylene glycol, 1,2-butylene glycol, 1,3-butylene glycol, tetramethylene glycol, 2,3-butylene glycol, pentamethylene glycol, 2-butene-1,4-diol, hexylene glycol, octylene glycol, etc.); trihydric alcohols (e.g., glycerin, trimethylolpropane, etc.); tetrahydric alcohols (e.g., pentaerythritol such as 1,2,6-hexanetriol, etc.); pentahydric alcohols (e.g., xylitol, etc.); hexahydric alcohols (e.g., sorbitol, mannitol, etc.); polyhydric alcohol polymers (e.g., diethylene glycol, dipropylene glycol, triethylene glycol, dihydric alcohol alkyl ethers (e.g., ethylene glycol monomethyl ether, ethylene glycol monoethyl ether, ethylene glycol monobutyl ether, ethylene glycol monophenyl ether, ethylene glycol monohexyl ether, ethylene glycol mono-2-methylhexyl ether, ethylene glycol isoamyl ether, ethylene glycol benzyl ether, ethylene glycol isopropyl ether, ethylene glycol dimethyl ether, ethylene glycol diethyl ether, ethylene glycol dibutyl ether, etc.);Dihydric alcohol alkyl ethers (e.g., diethylene glycol monomethyl ether, diethylene glycol monoethyl ether, diethylene glycol monobutyl ether, diethylene glycol dimethyl ether, diethylene glycol diethyl ether, diethylene glycol butyl ether, diethylene glycol methyl ethyl ether, triethylene glycol monomethyl ether, triethylene glycol monoethyl ether, propylene glycol monomethyl ether, propylene glycol monoethyl ether, propylene glycol monobutyl ether, propylene glycol isopropyl ether, dipropylene glycol methyl ether, dipropylene glycol ethyl ether, dipropylene glycol butyl ether, etc.); dihydric alcohol ether esters (e.g., ethylene glycol monomethyl ether acetate, ethylene glycol monoethyl ether acetate, ethylene glycol monobutyl ether acetate, ethylene glycol monophenyl ether acetate, ethylene glycol diadipate, ethylene glycol di succinate, diethylene glycol monoethyl ether acetate, diethylene glycol monobutyl ether acetate, propylene glycol monomethyl ether acetate, propylene glycol monoethyl ether acetate, propylene glycol monopropyl ether acetate, propylene glycol monophenyl ether acetate, etc.); glycerin monoalkyl ethers (e.g., xyl alcohol, selachyl alcohol, batyl alcohol, etc.); sugar alcohols (e.g., sorbitol, maltitol, maltotriol, etc.); Examples of suitable sugars include maltose, mannitol, sucrose, erythritol, glucose, fructose, starch-decomposed sugars, maltose, xylitose, starch-decomposed sugar-reduced alcohols, etc.; glysolid; tetrahydrofurfuryl alcohol; POE-tetrahydrofurfuryl alcohol; POP-butyl ether; POP·POE-butyl ether; tripolyoxypropylene glycerin ether; POP-glycerin ether; POP-glycerin ether phosphate; POP·POE-pentaneerythritol ether, and polyglycerin. These may be used alone or in combination of two or more.
[0070] Examples of monosaccharides include trioses (e.g., D-glyceryl aldehyde, dihydroxyacetone, etc.); tetraoses (e.g., D-erythrose, D-erythrulose, D-threose, erythritol, etc.); pentoses (e.g., L-arabinose, D-xylose, L-lyxose, D-arabinose, D-ribose, D-ribulose, D-xylulose, L-xylulose, etc.); hexoses (e.g., D-glucose, D-talose, D-busicose, D-galactose, D-fructose, L-galactose, L- mannose, D-tagatose, etc.); heptoses (e.g., aldoheptose, heprose, etc.); octose (e.g., octulose, etc.); deoxysugars (e.g., 2-deoxy-D-ribose, 6-deoxy-L-galactose, 6-deoxy-L-mannose, etc.); aminosugars (e.g., D-glucosamine, D-galactosamine, sialic acid, aminouronic acid, muramic acid, etc.); uronic acids (e.g., D-glucuronic acid, D-mannuronic acid, L-guluronic acid, D-galacturonic acid, L-iduronic acid, etc.). These may be used alone or in combination of two or more.
[0071] Examples of oligosaccharides include sucrose, gunthianose, umbelliferose, lactose, planteose, isolychnoses, α,α-trehalose, raffinose, lychnoses, umbilicin, stachyose, verbascoses, etc. These may be used alone or in combination of two or more.
[0072] Examples of polysaccharides include cellulose, quince seed, chondroitin sulfate, starch, galactan, dermatan sulfate, glycogen, gum arabic, heparan sulfate, hyaluronic acid, tragacanth gum, keratan sulfate, chondroitin, mucoitin sulfate, guar gum, dextran, keratosulfuric acid, locust bean gum, succinoglucan, and caronic acid. These may be used alone or in combination of two or more.
[0073] Examples of amino acids include neutral amino acids (e.g., threonine, cysteine, etc.); basic amino acids (e.g., hydroxylysine, etc.). Examples of amino acid derivatives include acyl sarcosine sodium (sodium lauroyl sarcosine), acyl glutamate, acyl β-alanine sodium, glutathione, pyrrolidone carboxylic acid, etc. These may be used alone or in combination of two or more.
[0074] Examples of organic amines include monoethanolamine, diethanolamine, triethanolamine, morpholine, triisopropanolamine, 2-amino-2-methyl-1,3-propanediol, 2-amino-2-methyl-1-propanol, etc. These may be used alone or in combination of two or more.
[0075] Examples of polymer emulsions include acrylic resin emulsions, polyethyl acrylate emulsions, acrylic resin liquids, polyacrylic alkyl ester emulsions, polyvinyl acetate resin emulsions, natural rubber latex, etc. These may be used alone or in combination of two or more.
[0076] Examples of pH adjusters include buffers such as citric acid, lactic acid-sodium lactate, citric acid-sodium citrate, and succinic acid-sodium succinate. These may be used alone or in combination of two or more. Examples of vitamins include vitamins A, B, and C. 1 , B 2 , B 6 , B 12 , C, D, E or derivatives thereof, pantothenic acid or derivatives thereof, biotin, etc. These may be used alone or in combination of two or more.
[0077] Examples of antioxidants include tocopherols, dibutylhydroxytoluene, butylhydroxyanisole, gallic acid esters, etc. These may be used alone or in combination of two or more.
[0078] Examples of antioxidant aids include phosphoric acid, citric acid, ascorbic acid, maleic acid, malonic acid, succinic acid, fumaric acid, cephalin, hexametaphosphate, phytic acid, ethylenediaminetetraacetic acid, etc. These may be used alone or in combination of two or more.
[0079] Other ingredients that can be added include, for example, preservatives (e.g., ethylparaben, butylparaben, chlorphenesin, phenoxyethanol, etc.); disinfectants (e.g., isopropylmethylphenol, benzalkonium chloride, benzethonium chloride, chlorhexidine gluconate, etc.); anti-inflammatory agents (e.g., glycyrrhizinic acid derivatives, glycyrrhetinic acid derivatives, salicylic acid derivatives, hinokitiol, zinc oxide, allantoin, etc.); whitening agents (e.g., placenta extract, saxifrage extract, , arbutin, etc.); various extracts (e.g., Phellodendron bark, Coptis chinensis, Lithospermum root, Peony, Birch, Sage, Loquat, Carrot, Aloe, Mallow, Iris, Grape, Job's tears, Luffa, Lily, Saffron, Cnidium rhizome, Angelica acutiloba, St. John's wort, Ononis, Garlic, Capsicum, Citrus fruit, Angelica acutiloba, Seaweed, etc.), activators (e.g., Royal jelly, photosensitizers, cholesterol derivatives, etc.); blood circulation promoters (e.g., nonylic acid valenylamide, nicotinic acid benzyl esters, nicotinic acid β-butoxyethyl ester, capsaicin, zingerone, cantharides tincture, ichthammol, tannic acid, α-borneol, tocopherol nicotinate, inositol hexanicotinate, cyclandelate, cinnarizine, tolazoline, acetylcholine, verapamil, cepharanthine, γ-oryzanol, etc.); antiseborrheic agents (e.g., sulfur, thianthol, etc.); anti-inflammatory agents (e.g., tranexamic acid, thiotaurine, hypotaurine, etc.) Examples of such agents include sequestering agents such as disodium edetate, trisodium edetate, sodium citrate, sodium polyphosphate, sodium metaphosphate, gluconic acid, and malic acid; caffeine, tannin, verapamil, tranexamic acid or a derivative thereof, and various herbal extracts such as licorice, Chinese quince, and Japanese anemone; whitening agents such as magnesium ascorbyl phosphate, ascorbyl glucoside, arbutin, and kojic acid; and amino acids or derivatives thereof such as arginine and lysine. These may be used alone or in combination of two or more.
[0080] The target area to which the composition for scalp and hair of the present invention is applied is the scalp and / or hair, and is used for hair care and growth, but it may also be used for hair care and growth of, for example, eyelashes, eyebrows, etc. The composition for scalp and hair of the present invention can be in the form of a product such as a hair tonic, hair liquid, hair rinse, hair conditioner, hair treatment, hair lotion, hair pack, hair cream, conditioning mousse, hair mousse, hair spray, shampoo, or leave-on treatment. The composition for scalp and hair of the present invention may belong to the category of any of pharmaceuticals, quasi-drugs, or cosmetics.
[0081] The composition for scalp and hair of the present invention can be applied externally in the form of a homogeneous solution, lotion, gel, etc., according to conventional methods. The composition for scalp and hair of the present invention can also be in the form of an aerosol, in which case it contains, in addition to the above-mentioned components, a lower alcohol such as n-propyl alcohol or isopropyl alcohol, a flammable gas such as butane, propane, isobutane, liquefied petroleum gas, or dimethyl ether, or a compressed gas such as nitrogen gas, oxygen gas, carbon dioxide gas, or nitrous oxide gas.
[0082] <Method of Use> The total amount of the ingredients (specific ozone-treated glycerin, or the cyclic peroxide represented by the above chemical formula (1) or a salt thereof) effective for achieving the effects of the composition for scalp and hair of the present invention is, for example, 0.000001 to 0.1 g per day for a typical adult. An amount of the composition for scalp and hair in this range (preferably 0.000001 to 0.05 g / application) is applied to the entire scalp several times a day (preferably 1 to 2 times) and massaged in. Furthermore, the composition for scalp and hair is preferably used according to the amount of hair, frequency of application, and dosage form.
[0083] The hair care agent and scalp and hair care composition of the present invention are preferably applied to humans, but can also be applied to animals other than humans as long as the respective functional effects are achieved.
[0084] (Animal Washing Composition) The animal washing composition used in the present invention contains the hair care agent of the present invention or the FGF-7 production promoter of the present invention, and further contains other ingredients as required.
[0085] <Hair-growth agent or FGF-7 production promoter> The hair-growth agent or FGF-7 production promoter is the hair-growth agent or FGF-7 production promoter of the present invention described above. The content of the hair-growth agent or FGF-7 production promoter is not particularly limited and can be selected as appropriate, but is preferably 0.01 mg / g or more, more preferably 0.1 mg / g or more, even more preferably 1 mg / g or more, particularly preferably 5 mg / g or more, and even more particularly preferably 10 mg / g or more, relative to the animal wash composition.
[0086] The animal washing composition may further contain other ingredients as needed, such as water, anionic surfactants, cationic surfactants, amphoteric surfactants, nonionic surfactants, moisturizers, water-soluble polymers, thickeners, film-forming agents, ultraviolet absorbers, sequestering agents, lower alcohols, polyhydric alcohols, oils, sugars, amino acids, organic amines, polymer emulsions, pH adjusters, skin nutrients, vitamins, plant extracts, antioxidants, antioxidant aids, fragrances, colorants, preservatives, disinfectants, insecticides, and pest repellent ingredients.
[0087] Animals to which the animal cleansing composition can be applied include non-human animals, such as pets such as cats, dogs, and rabbits, livestock such as cows, horses, pigs, sheep, and goats, and poultry such as ducks, chickens, and geese. Examples of animal cleansing compositions include soaps, shampoos, rinse-in shampoos, facial cleansers, rinses, lotions, animal hair care products, and animal hair growth agents.
[0088] Examples of the present invention will be described below, but the present invention is not limited to these examples. The content of each component is in mass % unless otherwise specified. In the following examples, the oxidizing power of ozone-treated glycerin converted into ozone concentration was measured as follows.
[0089] <Measurement of Oxidizing Power> The oxidizing power of the obtained ozone-treated glycerin was measured in terms of ozone concentration by potassium iodide titration. Specifically, potassium dihydrogen phosphate (KH2 P.O. 4 ) 17.90 g and disodium hydrogen phosphate (Na 2 HPO 4 ・12H 2 17.14 g of potassium iodide (KI) was added and dissolved, and then 25.00 g of potassium iodide (KI) was added and dissolved. The resulting solution was diluted with purified water to a total of approximately 500 g to prepare a potassium iodide absorption solution. Next, sodium thiosulfate (Na 2 S 2 O 3 Approximately 0.32 g of ozone-treated glycerin was diluted with purified water to a final weight of approximately 400 g and dissolved in purified water to prepare sodium thiosulfate. Furthermore, approximately 0.22 g of starch was added to approximately 20 g of purified water and boiled to dissolve, preparing a starch aqueous solution. Next, approximately 50 g of potassium iodide absorption solution was added to approximately 1 g (1.00 g to 1.20 g) of ozone-treated glycerin, and the mixture was stirred for 10 minutes on a stirrer set at 300 rpm and 0°C. After stirring, approximately 0.2 mL of starch aqueous solution was added. Using a funnel, the sodium thiosulfate solution was slowly added dropwise to the mixture after the addition of the starch aqueous solution until the mixture became colorless and transparent. The oxidizing power of the ozone-treated glycerin was calculated based on the following formula (A): O = (St × 24 × T) / S (A) O: oxidizing power of sample (ppm) St: concentration of sodium thiosulfate in sodium thiosulfate solution (mmol / L) S: amount of sample (g) T: titer of sodium thiosulfate solution (mL)
[0090] (Ozone-Treated Glycerin Production Example 1) High-concentration glycerin and ozone were brought into gas-liquid contact to produce high-oxidizing power ozone-treated glycerin. A 50-L Teflon (registered trademark) tank was used as the contact vessel. An air diffuser was installed on the bottom of the tank so that ozone could be supplied into the tank as fine bubbles. A silent discharge ozone generator (manufactured by Mediplus Pharmaceutical Co., Ltd.) capable of generating 100 g of ozone per hour using oxygen at a concentration of 90% by volume or more as the raw material was used as the ozone generator. 22 kg of high-concentration glycerin (glycerin at a concentration of 98% by mass or more as specified in the Japanese Pharmacopoeia) was placed in the tank, and 20 L of oxygen was fed into the silent discharge ozone generator at a rate of 20 L per minute. The generated ozone-containing gas was released from the air diffuser into the tank for 5 days (aeration conditions), yielding ozone-treated glycerin (hereinafter sometimes referred to as "OG2000") with an oxidizing power of 2,000 ppm in terms of ozone concentration. The obtained "OG2000" contained the cyclic peroxide represented by the above general formula (1), as will be described later.
[0091] (Ozone-treated glycerin Production Example 2) An ozone-treated glycerin (hereinafter, sometimes referred to as "OG500") having an oxidizing power, calculated as an ozone concentration, of 500 ppm was obtained in the same manner as in ozone-treated glycerin Production Example 1, except that the aeration conditions in ozone-treated glycerin Production Example 1 were changed to release for one day. The obtained "OG500" contained the cyclic peroxide represented by the above general formula (1), similar to the above "OG2000".
[0092] (Ozone-treated glycerin Production Example 3) An ozone-treated glycerin (hereinafter, sometimes referred to as "OG200") having an oxidizing power, calculated as an ozone concentration, of 200 ppm was obtained in the same manner as in ozone-treated glycerin Production Example 1, except that the aeration conditions in ozone-treated glycerin Production Example 1 were changed to 12-hour release. The obtained "OG200" contained the cyclic peroxide represented by the above general formula (1), just like the above "OG2000."
[0093] (Ozone-treated Glycerin Production Example 4) A low-oxidizing-power ozone-treated glycerin (hereinafter, sometimes referred to as "OG100") having an oxidizing power of 100 ppm in terms of ozone concentration was obtained in the same manner as in Ozone-treated Glycerin Production Example 1, except that the aeration conditions in Ozone-treated Glycerin Production Example 1 were changed to 6-hour release. The obtained "OG100" contained the cyclic peroxide represented by the above general formula (1), similar to the above "OG2000".
[0094] (Ozone-Treated Glycerin Production Example 5) The "OG2000" obtained in Ozone-Treated Glycerin Production Example 1 was diluted with high-concentration glycerin (untreated glycerin with a concentration of 98% by mass or more according to the Japanese Pharmacopoeia) at room temperature to an oxidizing power of 50 ppm in terms of ozone concentration, to obtain diluted low-oxidizing-power ozone-treated glycerin (hereinafter sometimes referred to as "OG50"). The obtained "OG50", like the above "OG2000", contained the cyclic peroxide represented by the above general formula (1).
[0095] <Analysis of Reaction Mixture> Glycerin was removed from the ozone-treated glycerin solution produced in Production Example 1 of Ozone-Treated Glycerin using a silica gel column to obtain a reaction mixture (hereinafter, sometimes referred to as "TLC 1 spot product").
[0096] The NMR spectrum of the reaction mixture (TLC 1 spot) was measured using DMSO-d 6 The measurements were carried out at a temperature of 300 K (27°C) using the solvent. The spectra are shown in Figures 1 to 6. 1 1 H NMR spectrum. 13 3 is a C NMR spectrum diagram. 13 FIG. 4 is a C DEPT135 NMR spectrum. FIG. 4 is a COSY NMR spectrum. FIG. 5 is an HSQC NMR spectrum. FIG. 6 is an HMBC NMR spectrum. As shown in FIGS. 1 to 6, complex peaks were observed, suggesting that the TLC1 spot product was a mixture of multiple substances. Furthermore, LCMS revealed that the TLC1 spot product contained components with m / z 198 and 203.
[0097] <Separation and Analysis of Reaction Mixture> The reaction mixture (TLC 1 spot product) was diluted to approximately 3% by mass with acetonitrile, filtered through a membrane filter, and the filtrate was subjected to LC measurement to optimize the separation conditions. Next, the mass of the peak observed in the LC measurement under the optimized conditions was confirmed, and precision fractionation of Mw = 180 (peak 2) was performed. The obtained fraction solution was then freeze-dried, and the dried fraction was subjected to microscopic LR measurement and various NMR measurements. The measurement equipment (analyzer) and measurement conditions are as follows.
[0098] [Measuring equipment (analyzer)] 1) Precision preparative LC: Waters, ACQUITY UPLC H-class Bio 2) Microscope LR: SNOM / AFM / Raman complex machine alpha300RSA manufactured by WITec 3) NMR: Bruker Biospin, AVANCE III-600 with Cryo Probe
[0099] [Measurement conditions] 1) Precision preparative LC Column: Shodex Asahipak NH 2 P-50 (4.6 mmφ×250 mm, 5 μm) Eluent composition: water / acetonitrile gradient Time (min): 0 5 15 20 Water: 5 10 50 50 Acetonitrile: 95 90 50 50 Flow rate: 1.0 mL / min Detector: MS (QDa) Column temperature: 40°C Injection volume: 50 μL Ionization method: ESI (NEG.) Measurement mass range (m / z): 50 to 500 2) Microscope LR Excitation wavelength: 532 nm Measurement wavenumber range: approximately 125 to 3800 cm -1 Objective lens: ×100 Detector: EMCCD 3) NMR observation frequency: 600 MHz ( 1 H), 150MHz ( 13 C) Measurement solvent: methanol-d 4 Measurement temperature: 300 K Chemical shift standard: Measurement solvent [3.30 ppm ( 1 H), 49.80ppm ( 13 C) ]
[0100] FIG. 7 shows total ion chromatograms (ESI-negative mode) obtained by the precision preparative LC (liquid chromatography) of a sample prepared by diluting the reaction mixture (TLC1 spot product) with acetonitrile to approximately 3% by mass, and a blank. In FIG. 7, the vertical axis represents intensity, and the horizontal axis represents retention time (minutes). In FIG. 7, the lower row of "Synthetic OG" is a chromatogram of the TLC1 spot product sample, and the upper row is a chromatogram of the blank (acetonitrile). As shown in the figure, components A to L were confirmed in the TLC1 spot product. Components A to L were separated and examined for coloration using potassium iodide starch test paper. Component H showed the strongest coloration.
[0101] Figure 8 also shows the mass spectra of peaks F, G, and H (F fraction, G fraction, and H fraction) in Figure 7. In Figure 8, the vertical axis represents intensity, and the horizontal axis represents mass-to-charge ratio (m / z). As shown in the figure, it was confirmed that peak F had Mw = 180, peak G had Mw = 226, and peak H had Mw = 256.
[0102] Furthermore, Figure 9 shows the results of an investigation into the improvement of separation (improvement of separation conditions) in HILIC (high performance liquid chromatography). In Figure 9, the vertical axis represents intensity, and the horizontal axis represents retention time (minutes), as in Figures 17 to 19. In Figure 9, the upper row is a chromatogram before separation improvement (under the same conditions as in Figure 2-10), and the lower row is a chromatogram after separation improvement. As shown in the figure, peaks 1 to 8 were observed after separation improvement. The molecular weights of each peak were confirmed to be the molecular weights shown in Figure 9 using mass spectrometry, which will be described later.
[0103] Figure 10 shows the mass spectra (after improved separation) of peaks 1 to 3 in Figure 9. In Figure 10, the upper row is the mass spectrum of peak 1, the middle row is the mass spectrum of peak 2, and the lower row is the mass spectrum of peak 3. As shown in the figure, it was confirmed that peak 1 had Mw = 196, peak 2 had Mw = 180, and peak 3 had Mw = 240.
[0104] Figure 11 shows the mass spectra (after improved separation) of peaks 4 to 6 in Figure 9. In Figure 11, the upper row is the mass spectrum of peak 4, the middle row is the mass spectrum of peak 5, and the lower row is the mass spectrum of peak 6. As shown in the figure, it was confirmed that peak 4 had Mw = 240, peak 5 had Mw = 240, and peak 6 had Mw = 226.
[0105] Figure 12 shows the mass spectra (after improved separation) of peaks 7 and 8 in Figure 9. In Figure 12, the upper part is the mass spectrum of peak 7, and the lower part is the mass spectrum of peak 8. As shown in the figure, it was confirmed that both peaks 7 and 8 had Mw = 256.
[0106] FIG. 13 also shows the micro-Raman spectra of a sample obtained by separating peak 2 (Mw=180) in FIG. 9 and of an ozonide standard (ozonized oleic acid). In FIG. 13, the vertical axis represents intensity, and the horizontal axis represents Raman shift (1 / cm). As shown in FIG. 13, peak 2 (Mw=180) exhibited a micro-Raman spectrum similar to that of ozonide, and therefore it was presumed to exhibit a structure similar to that of ozonide. Furthermore, the micro-Raman spectrum of peak 2 (Mw=180) exhibited a pattern different from that of peroxide, and therefore it was presumed that peak 2 (Mw=180) was not a peroxide. Peak 2 (Mw=180) was confirmed to be the cyclic peroxide by NMR, which will be described later.
[0107] FIG. 14 shows the peak 2 (Mw=180) in FIG. 1 The H NMR spectrum is shown. The measurement solvent was methanol-d 4 (CD 3 In the figure, the upper spectrum is an enlarged view of the lower spectrum around 3.4 to 4.9 ppm. 1 Based on the H NMR assignments, the Mw=180, and other instrumental analysis data, it was demonstrated that the structure of the oxidation reaction product of peak 2 (Mw=180) was a cyclic peroxide represented by the following chemical formula (1). 1In the H NMR spectrum, the peaks indicated by symbols A to F were assigned to the peaks of hydrogen bonded to the carbon atoms indicated by the same symbols A to F in the following chemical formula (1) shown in Figure 14. It is also presumed that a small amount of glycerin, the raw material, remained, and its peak was also detected.
[0108]
[0109] FIG. 15 shows the peak 2 (Mw=180) in FIG. 13 The C NMR spectrum is shown. The measurement solvent was methanol-d 4 (CD 3 In the figure, the upper spectrum is an enlarged view of the lower spectrum around 60 to 105 ppm. 13 Based on the C NMR assignment, the Mw=180, and other instrumental analysis data, it was demonstrated that the structure of the oxidation reaction product of peak 2 (Mw=180) was the cyclic peroxide represented by the above chemical formula (1). 13 In the C NMR spectrum, the peaks indicated by symbols A to F were assigned to the peaks of carbon atoms indicated by the same symbols A to F in the above chemical formula (1) shown in Figure 15. It is also presumed that a small amount of glycerin, the raw material, remained and its peak was also detected.
[0110] FIG. 16 shows the two-dimensional ( 1 H- 13 The C COSY NMR spectrum is shown. The measurement solvent was methanol-d 4 (CD 3 OD) was used. Based on this 2D NMR assignment, the fact that Mw = 180, and other instrumental analysis data, it was demonstrated that the structure of the oxidation reaction product of peak 2 (Mw = 180) was a cyclic peroxide represented by the above-mentioned chemical formula (1). In the 2D NMR spectrum diagram of FIG. 16, the peaks indicated by symbols A to F were respectively assigned to the peaks of carbon atoms and hydrogen atoms bonded to those carbon atoms represented by the same symbols A to F in the above-mentioned chemical formula (1) shown in FIG. 16. It is also presumed that a small amount of the raw material glycerin remained, and that its peak was also detected.
[0111] Figure 17 also shows HILIC (high performance liquid chromatography) chromatograms of the TLC1 spot product and glyceraldehyde dimer under the HILIC conditions of Figure 9. In Figure 17, the "synthetic OG" in the upper row is a HILIC chromatogram of the TLC1 spot product. The lower row is a HILIC chromatogram with glyceraldehyde dimer. As shown in the figure, glyceraldehyde dimer was not detected under the HILIC conditions of Figure 9.
[0112] Figure 18 also shows HILIC chromatograms of the TLC1 spot product and glyceraldehyde dimer under reversed-phase HILIC (high-performance liquid chromatography) conditions. Figure 19 shows an enlarged view of a portion of Figure 18. In Figures 18 and 19, the "synthetic OG" in the upper row is a HILIC chromatogram of the TLC1 spot product. The lower row is a HILIC chromatogram with glyceraldehyde dimer. As shown, under reversed-phase HILIC conditions, separation of the components of the TLC1 spot product was not confirmed. This is thought to be due to the weak retention of the column, resulting in a fast elution time for the TLC1 spot product. Meanwhile, the retention time of glyceraldehyde dimer was slightly different from that of the TLC1 spot product (synthetic OG). From this, it is inferred that the TLC1 spot product did not contain glyceraldehyde dimer.
[0113] Figure 20 also shows the ESR spectrum of the TLC1 spot sample and peak 2 (Mw = 180) in Figure 9. In Figure 20, the vertical axis represents intensity and the horizontal axis represents magnetic flux density (G). Water was used as the measurement solvent. As shown in the figure, the spectra of the TLC1 spot sample and peak 2 (Mw = 180) component in Figure 9 almost completely overlap, and the peak positions are almost completely identical in both cases. Both the TLC1 spot sample and peak 2 (Mw = 180) component in Figure 9 showed the spectrum of DMPO (spin trap agent) characterized by six lines. This spectral pattern is similar to that of ozonide.
[0114] Figure 21 shows the ESR spectrum of ozonized methyl linolenate. Acetone was used as the measurement solvent. Ozonized methyl linolenate is well known. As shown in the figure, the ESR spectrum of ozonized methyl linolenate shows a spectrum in the presence of DMPO (a spin trapping agent) that features six lines characteristic of ozonides. This spectral pattern is similar to the patterns of the TLC1 spot and peak 2 (Mw = 180) in Figure 20.
[0115] Figure 22 shows the ESR spectrum of peaks 1 to 8 in Figure 9. Water was used as the measurement solvent. The top ESR spectrum is of a blank (solvent only) for comparison. As shown in the figure, it was confirmed that all of the components of peaks 1 to 8 have radical activity.
[0116] The graph in Figure 23 shows the results of measuring the activity of peaks 1 to 8 in Figure 9 by chemiluminescence. In this figure, the vertical axis represents the luminescence intensity (relative intensity) at all wavelengths. The numbers "1" to "8" on the horizontal axis represent the fractions of peaks 1 to 8. The numbers below each number represent the molecular weight of each fraction as confirmed by mass spectrometry. As shown in the figure, it was confirmed that components other than the one with a molecular weight of 180 were produced that showed activity by chemiluminescence.
[0117] <Evaluation of FGF-7 growth factor expression using human dermal papilla cells> Dermal papilla cells were cultured in a 96-well plate coated with type I collagen using Dulbecco's modified MEM containing 10% fetal bovine serum (10% FBS-DMEM) at a density of 1.5 × 10 4 The cells were seeded at a cell density of 1000 cells / well and cultured for 48 hours (37°C, 5% CO 2) After removing the medium, the cells were replaced with the test samples shown in Table 1 below and cultured for 48 hours. The culture supernatant was collected and subjected to ELISA. ELISA was performed by the sandwich method using a commercially available kit (DKG00 (KGF / FGF7), manufactured by R&D Systems). Human dermal papilla cells were lysed in 0.5% Triton X-100 solution, and the total protein amount was quantified using a BCATM Protein Assay kit (manufactured by Takara Bio Inc.). The amount of FGF-7 was calculated as the amount per unit protein amount. The amount of FGF-7 was expressed as the average value, and statistical analysis was performed using an unpaired Student's t-test, with a p value of less than 0.05 (p<0.05) being considered statistically significant.
[0118] From the results in Table 1, it was confirmed that "OG200" and "OG500" had a high FGF-7 production promoting effect at concentrations of 0.01 to 1%.
[0119] <Hair-growth test> The hair-growth effect, such as improvement of hair loss, was confirmed by the hair-growth test shown below. Hair density was measured as the index most likely to be parallel when improving hair loss, and the reduction in telogen hair, hair density, changes in hair growth rate, and improvement of scalp condition were evaluated.
[0120] - Subjects - 30 women aged 40 to 60 who were concerned about thinning hair and hair loss (10 people in each sample, divided into 3 groups). During the hair growth test, the subjects were instructed not to undergo any treatment that would affect the target areas, to avoid excessive exposure to ultraviolet rays through outdoor activities such as swimming in the sea, mountain climbing, or sunbathing, not to start taking any new supplements, and to maintain a normal lifestyle by avoiding overeating and drinking.
[0121] - Evaluation items - ・Visual evaluation of thinning hair: At the start of the test, a research specialist visually checked the areas where the subject had assessed hair thinning. ・Analysis of scalp condition using the phototrichogram method ・Photography of the scalp using a digital microscope ・Questionnaire survey
[0122] - Duration - 12 weeks (3 months)
[0123] - Sample (hair growth agent) - The compositions of Samples R, D, and C used in the hair growth test are as shown in Table 2 below. Note that the 0.001% by mass of Swertia japonica extract in Sample R is a content that does not affect the effect.
[0124] * 1: OG500: Ozone-treated glycerin produced in Production Example 1 of ozone-treated glycerin, oxidizing power equivalent to 500 ppm in ozone concentration * 2: Glycerin with a concentration of 98% by mass or more; Japanese Pharmacopoeia product * 3: Swertia japonica extract; manufactured by Maruzen Pharmaceutical Co., Ltd. * 4: Pyrrolidinyldiaminopyrimidine oxide; manufactured by Horus Co., Ltd. * 5: Pentylene glycol, butylene glycol (BG), PEG-60 hydrogenated castor oil, methyl gluceth-10, glycyrrhizinate 2K, 1,2-hexanediol, caprylyl glycol, citric acid, sodium citrate, purified water (same for samples R, D, and C)
[0125] -How to use- After washing the hair once a day, dry the hair thoroughly, then fill each sample into a hair growth jet spray container, drop an appropriate amount (1.5 mL) onto the scalp, and apply it to the target area.
[0126] <Analysis of scalp condition using phototrichogram method> A 5mm area in length and width was shaved on any part of the scalp, and the scalp condition (hair density, hair diameter measurement, hair growth rate, growth phase hair rate, number of telogen hairs, etc.) was analyzed by phototrichogram method using a Tricoscan manufactured by Integral Corporation. The results comparing before and after 12 weeks of use are shown in Table 3. The results comparing Sample C with Sample R and Sample D are shown in Table 4. The results comparing Sample R with Sample D are shown in Table 5. [Evaluation criteria] ↓ or ↑: direction as mean value ↓↓ or ↑↑: trend (p<0.1) ↓↓↓ or ↑↑↑: significant difference (p<0.05)
[0127] <Comparison before and after 12 weeks of use>
[0128]
[0129] <Comparison of Sample C with Sample R and Sample D>
[0130]
[0131] <Comparison between Sample R and Sample D>
[0132]
[0133] From the results in Tables 3 to 5, the following hair-growth effects were confirmed. - Regarding hair diameter - After 12 weeks, a significant difference was observed in the measured hair diameter between the group using Sample D and the group using Sample R (hair was less likely to thin with Sample R) - A significant change was observed in the measured hair diameter in the group using Sample D after 12 weeks compared to before use (hair was thinner with Sample D) - Regarding hair growth rate - After 12 weeks, a significant difference was observed in the measured hair growth rate between the group using Sample C and the group using Sample R (hair grew faster with Sample R) - Regarding the number of telogen hairs - After 12 weeks, a significant difference was observed in the measured number of telogen hairs between the group using Sample C and the group using Sample R (fewer hairs had stopped growing with Sample R).
[0134] From the above, it was found that Sample R had an excellent hair-growth effect, as it inhibited the decrease in hair diameter, increased hair growth rate, and reduced the number of telogen hairs. It was also found that Sample D had a good hair-growth effect.
[0135] <Photographing the scalp with a digital microscope> (1) For each of Sample R, Sample D, and Sample C, one subject was shaved in a section of hair (1 cm x 1 cm), and the shaved section was photographed with a digital microscope (VHX-7000, manufactured by Keyence Corporation, 20-200x zoom lens (VH-Z20T, manufactured by Keyence Corporation)) immediately after shaving and three days later (images taken before sample use). (2) After washing their hair twice a day, 1.25 mL of each of Sample R, Sample D, and Sample C was applied to the entire scalp, including the shaved section, and massaged to spread the entire scalp, focusing on the measurement area, for 12 weeks. (3) After 12 weeks of use, the same sections as those shaved before application of Sample R, Sample D, and Sample C were shaved again, and the sections were photographed with a digital microscope immediately after shaving and three days later (images taken after sample use). (4) Photographs taken before use (after 3 days) and after 12 weeks of use (after 3 days) are shown in Figures 24 to 26. A specialist researcher observed the scalp condition from these images. As a result, it was confirmed that Samples R and D had a hair-growth effect.
[0136] <Questionnaire Survey> Thirty subjects were asked to rate the items "Spray container," "On the scalp," "On the hair," and "Finish" shown in Table 6 on a 5-point scale from 0 to 5 (0: very bad, 5: very good). The results of the questionnaire after 12 weeks are shown in Table 6. The values in Table 6 are the average values for the 30 subjects.
[0137] From the results in Table 6, it can be seen that Samples R and D have a hair-growth effect, and Sample D gave better results than Sample R.
[0138] Below are examples of formulations of scalp and hair compositions containing ozone-treated glycerin "OG50," "OG100," "OG200," "OG500," or "OG2000." Each formulation had a good hair-growth effect based on "OG50," "OG100," "OG200," "OG500," or "OG2000."
[0139] (Formulation Example 1) <O / W emulsion-type hair care product> [Phase A] Polyoxyethylene (60 mol) hydrogenated castor oil: 2.0% by mass Glycerin: 10.0% by mass OG2000: 0.1% by mass Dipropylene glycol: 10.0% by mass 1,3-butylene glycol: 5.0% by mass Polyethylene glycol 1500: 5.0% by mass [Phase B] Cetyl isooctanoate: 10.0% by mass Squalane: 5.0% by mass Vaseline: 2.0% by mass Propylparaben: 2.0% by mass [Phase C] 1% aqueous solution of carboxyvinyl polymer: 30.0% by mass Sodium hexametaphosphate: 0.03% by mass Ion-exchanged water: 8.35% by mass [Phase D] Caustic potassium: 0.12% by mass Ion-exchanged water: balance [Manufacturing method] Phases A and B were each heated to 60°C for dissolution, mixed, and processed in a homomixer to prepare a gel. Next, dissolved phase C was added to this, and finally dissolved phase D was added, and the mixture was emulsified in a homomixer to obtain an O / W emulsion-type hair care product.
[0140] (Formulation Example 2) <Cream-type hair care product> [Phase A] Liquid paraffin: 5.0 mass % Cetostearyl alcohol: 5.5 mass % Glyceryl monostearate: 3.0 mass % OG500: 0.5 mass % Propylparaben: 0.3 mass % Fragrance: 0.1 mass % [Phase B] Vitamin E succinate: 5.0 mass % Glycerin: 8.0 mass % Dipropylene glycol: 20.0 mass % Polyethylene glycol 4000: 5.0 mass % Sodium dodecyl sulfate 0.1 mass % Sodium hexametaphosphate: 0.005 mass % Ion-exchanged water: 45.095 mass % [Manufacturing method] Phases A and B were heated, dissolved, and mixed, and the mixture was emulsified using a homomixer to obtain a cream-type hair care product.
[0141] (Formulation Example 3) <Liquid hair care product> OG200: 1.0% by mass Stearyldimethylamine oxide: 0.5% by mass Hydrogenated castor oil ethylene oxide (40 mol) adduct: 1.0% by mass 95% ethanol: 54.0% by mass Ion-exchanged water: balance [Manufacturing method] Ion-exchanged water was added to 95% ethanol, and then the hydrogenated castor oil ethylene oxide (40 mol) adduct and stearyldimethylamine oxide were added thereto, followed by addition of OG200 and stirring to dissolve, thereby obtaining a liquid hair care product.
[0142] (Formulation Example 4) <Liquid hair care product> N-coconut lauryl-β-aminopropionic acid sodium: 0.2% by mass OG2000: 0.1% by mass Sodium dodecylbenzenesulfonate: 0.5% by mass Hydrogenated castor oil ethylene oxide (40 mol) adduct: 1.0% by mass 95% ethanol: 54.0% by mass Ion-exchanged water: balance [Manufacturing method] Ion-exchanged water was added to 95% ethanol, and to this was added hydrogenated castor oil ethylene oxide (40 mol) adduct, sodium dodecylbenzenesulfonate, and N-coconut lauryl-β-aminopropionic acid sodium, followed by addition of OG2000 and stirring to dissolve, thereby obtaining a liquid hair care product.
[0143] (Formulation Example 5) <Liquid hair care product> N-coconut lauryl-β-aminopropionic acid sodium: 0.2% by mass OG100: 1.0% by mass Sodium dodecylbenzenesulfonate: 0.5% by mass Hydrogenated castor oil ethylene oxide (40 mol) adduct: 1.0% by mass 95% ethanol: 54.0% by mass Ion-exchanged water: balance [Manufacturing method] Ion-exchanged water was added to 95% ethanol, and to this was added hydrogenated castor oil ethylene oxide (40 mol) adduct, sodium dodecylbenzenesulfonate, and N-coconut lauryl-β-aminopropionic acid sodium, followed by addition of OG2000 and stirring to dissolve, thereby obtaining a liquid hair care product.
[0144] (Formulation Example 6) <Hair Lotion> [Phase A] Sorbitol: 3.0% by mass Glycerin: 5.0% by mass Resorcinol: 0.02% by mass Ion-exchanged water: balance [Phase B] OG500: 0.5% by mass Polyoxyethylene (60) hydrogenated castor oil: 0.5% by mass 95% ethanol: 20.5% by mass Fragrance: appropriate amount [Manufacturing Method] The components of Phase A were mixed and dissolved, and the mixed solution of Phase B was added to this while stirring to obtain a homogeneous solution, thereby obtaining a hair cream.
[0145] (Formulation Example 7) <Hair Cream> [Phase A] Beeswax: 10.0% by mass Paraffin wax: 6.0% by mass Lanolin: 3.0% by mass Isopropyl myristate: 6.0% by mass Squalane: 8.0% by mass Liquid paraffin: 26.0% by mass Polyoxyethylene sorbitan stearate: 2.0% by mass Sorbitan monostearate: 4.2% by mass Preservative: appropriate amount [Phase B] Propylene glycol: 2.0% by mass Polyoxyethylene (60) hydrogenated castor oil: 1.0% by mass OG200: 1.0% by mass Purified water: balance [Manufacturing Method] The ingredients of phase A were mixed and dissolved by heating at approximately 75°C, and the mixed liquid of phase B heated to 75°C was added to this while stirring, and then the mixture was cooled to 45°C while continuing to stir, and left to stand to obtain a hair cream.
[0146] (Formulation Example 8) <Hair tonic> OG200: 0.5% by mass Peppermint (1,3-butylene glycol solution): 0.1% by mass N,N-dimethyl-2-dodecylamine oxide: 1.0% by mass Hinokitiol: 1.0% by mass Vitamin B 6 : 0.2 mass% Vitamin E acetate: 0.02 mass% Menthol: 0.2 mass% Swertia japonica extract: 1.0 mass% Salicylic acid: 0.1 mass% Mica squid (ethanol extract): 0.5 mass% Propylene glycol: 2.0 mass% Sodium hyaluronate: 0.01 mass% Polyoxyethylene (10 mol) monostearate: 2.0 mass% 75% ethanol: balance [Manufacturing method] The above ingredients were added sequentially to 75% ethanol, stirred and dissolved to obtain a hair tonic.
[0147] (Formulation Example 9) <Hair tonic> OG500: 0.5% by mass N,N-dimethyl-2-tetradecylamine oxide: 0.05% by mass Hinokitiol: 1.0% by mass Vitamin B 6 : 0.2% by mass Vitamin E acetate: 0.02% by mass Menthol: 0.2% by mass Salicylic acid: 0.1% by mass Pueraria lobata (ethanol extract): 0.5% by mass Propylene glycol: 0.01% by mass Sodium hyaluronate: 0.01% by mass Polyoxyethylene (10 mol) monostearate: 2.0% by mass 70% ethanol: balance [Manufacturing method] The above ingredients were added sequentially to 70% ethanol, stirred and dissolved to obtain a hair tonic.
[0148] Formulation Example 10 Hair tonic OG50: 1.0% by mass Peppermint (1,3-butylene glycol solution): 0.1% by mass N,N-dimethyl-2-dodecylamine oxide: 1.0% by mass Hinokitiol: 1.0% by mass Vitamin B 6 : 0.2 mass% Vitamin E acetate: 0.02 mass% Menthol: 0.2 mass% Swertia japonica extract: 1.0 mass% Salicylic acid: 0.1 mass% Mica squid (ethanol extract): 0.5 mass% Propylene glycol: 2.0 mass% Sodium hyaluronate: 0.01 mass% Polyoxyethylene (10 mol) monostearate: 2.0 mass% 75% ethanol: balance [Manufacturing method] The above ingredients were added sequentially to 75% ethanol, stirred and dissolved to obtain a hair tonic.
[0149] (Formulation Example 11) <Aerosol hair care product> [Concentrated formulation] OG2000: 0.1% by mass 95% ethanol: 50.0% by mass Glycyrrhetinic acid: 0.1% by mass Peppermint (ethanol extract): 0.05% by mass Swertia japonica extract: 0.1% by mass Sodium lauryl sulfate: 0.1% by mass N,N-dihydroxymethyl-2-decylamine oxide: 0.2% by mass Hydrogenated castor oil ethylene oxide (40 mol) adduct: 0.5% by mass Lactic acid: appropriate amount Sodium lactate: appropriate amount Fragrance: appropriate amount Colorant: appropriate amount Purified water: balance [Filling formulation] Concentrated solution: 50.0% by mass Liquefied petroleum gas: 50.0% by mass [Manufacturing method] After dissolving the concentrated formulation, this was filled into a can, a valve was attached, and gas was filled to obtain an aerosol hair care product.
[0150] (Formulation Example 12) <Hair-restoring shampoo> Sodium POE alkyl ether sulfate: 2.0% by mass Sodium ether carboxylate: 6.0% by mass Sodium POE alkyl sulfosuccinate: 1.0% by mass Alkylamidopropyl betaine: 8.0% by mass Alkyldimethylamine oxide: 3.0% by mass Fatty acid monoethanolamide: 5.0% by mass POE methyl glucoside dioleate: 0.4% by mass Cationic guar gum: 0.4% by mass Hydrolyzed protein: 0.5% by mass Butyl glycol: 1.0% by mass OG200: 0.5% by mass Preservative: appropriate amount Fragrance: appropriate amount Purified water: balance [Manufacturing method] The above ingredients were added sequentially to purified water, stirred and dissolved to obtain a hair-restoring shampoo.
[0151] (Formulation Example 13) <Hair-restoring shampoo> Sodium POE alkyl ether sulfate: 2.0% by mass Sodium ether carboxylate: 6.0% by mass Sodium POE alkyl sulfosuccinate: 1.0% by mass Alkylamidopropyl betaine: 8.0% by mass Alkyldimethylamine oxide: 3.0% by mass Fatty acid monoethanolamide: 5.0% by mass POE methyl glucoside dioleate: 0.4% by mass Cationic guar gum: 0.4% by mass Hydrolyzed protein: 0.5% by mass Butyl glycol: 1.0% by mass OG50: 1.0% by mass Preservative: appropriate amount Fragrance: appropriate amount Purified water: balance [Manufacturing method] The above ingredients were added successively to purified water, stirred and dissolved to obtain a hair-restoring shampoo.
[0152] (Formulation Example 14) <Hair-restoring rinse> Propylene glycol: 5.0% by mass Hydroxybenzophenone: 0.1% by mass Isostearyl myristate: 1.0% by mass Stearyltrimethylammonium chloride: 1.0% by mass Stearyl alcohol: 3.0% by mass POE (20 mol) hydrogenated castor oil: 1.0% by mass OG500: 0.5% by mass Preservative: appropriate amount Fragrance: appropriate amount Purified water: balance [Manufacturing method] The above ingredients were added sequentially to purified water, stirred and dissolved to obtain a hair-restoring rinse.
[0153] (Formulation Example 15) <Hair-restoring rinse> Propylene glycol: 5.0% by mass Hydroxybenzophenone: 0.1% by mass Isostearyl myristate: 1.0% by mass Stearyltrimethylammonium chloride: 1.0% by mass Stearyl alcohol: 3.0% by mass POE (20 mol) hydrogenated castor oil: 1.0% by mass OG100: 1.0% by mass Preservative: appropriate amount Fragrance: appropriate amount Purified water: balance [Manufacturing method] The above ingredients were added sequentially to purified water, stirred and dissolved to obtain a hair-restoring rinse.
[0154] (Formulation Example 16) <Animal shampoo> Sodium alkylbenzene sulfone: 6.0% by mass Coconut oil fatty acid amide prohydroxysulfopropyl betaine: 3.0% by mass Cationic cellulose: 0.1% by mass Sorbitol: 3.0% by mass Ethanol: 3.0% by mass OG2000: 0.3% by mass Sodium benzoate: 0.5% by mass pH adjuster: appropriate amount Fragrance: 0.3% by mass Purified water: balance [Manufacturing method] The above ingredients were added sequentially to purified water, and the mixture was stirred and dissolved to obtain an animal shampoo.
[0155] (Formulation Example 17) <Animal shampoo> Sodium alkylbenzene sulfone: 6.0% by mass Coconut oil fatty acid amide prohydroxysulfopropyl betaine: 3.0% by mass Cationic cellulose: 0.1% by mass Sorbitol: 3.0% by mass Ethanol: 3.0% by mass OG500: 0.5% by mass Sodium benzoate: 0.5% by mass pH adjuster: appropriate amount Fragrance: 0.3% by mass Purified water: balance [Manufacturing method] The above ingredients were added sequentially to purified water, and the mixture was stirred and dissolved to obtain an animal shampoo.
[0156] (Formulation Example 18) <Animal shampoo> Sodium alkylbenzene sulfone: 6.0% by mass Coconut oil fatty acid amide prohydroxysulfopropyl betaine: 3.0% by mass Cationic cellulose: 0.1% by mass Sorbitol: 3.0% by mass Ethanol: 3.0% by mass OG200: 0.7% by mass Sodium benzoate: 0.5% by mass pH adjuster: appropriate amount Fragrance: 0.3% by mass Purified water: balance [Manufacturing method] The above ingredients were added sequentially to purified water, and the mixture was stirred and dissolved to obtain an animal shampoo.
[0157] (Formulation Example 19) <Animal shampoo> Sodium alkylbenzene sulfone: 6.0% by mass Coconut oil fatty acid amide prohydroxysulfopropyl betaine: 3.0% by mass Cationic cellulose: 0.1% by mass Sorbitol: 3.0% by mass Ethanol: 3.0% by mass OG100: 1.0% by mass Sodium benzoate: 0.5% by mass pH adjuster: appropriate amount Fragrance: 0.3% by mass Purified water: balance [Manufacturing method] The above ingredients were added sequentially to purified water and dissolved by stirring to obtain an animal shampoo.
[0158] (Formulation Example 20) <Animal shampoo> Sodium alkylbenzene sulfone: 6.0% by mass Coconut oil fatty acid amide prohydroxysulfopropyl betaine: 3.0% by mass Cationic cellulose: 0.1% by mass Sorbitol: 3.0% by mass Ethanol: 3.0% by mass OG50: 2.0% by mass Sodium benzoate: 0.5% by mass pH adjuster: appropriate amount Fragrance: 0.3% by mass Purified water: balance [Manufacturing method] The above ingredients were added sequentially to purified water, and the mixture was stirred and dissolved to obtain an animal shampoo.
Claims
1. A hair care product comprising ozone-treated glycerin having an oxidizing power of 10 ppm or more and 5,000 ppm or less, calculated as an ozone concentration.
2. A hair care agent comprising a cyclic peroxide represented by the following chemical formula (1) or a salt thereof:
3. An FGF-7 production promoter, comprising ozone-treated glycerin having an oxidizing power, calculated as an ozone concentration, of 0.02 ppm or more and 5,000 ppm or less.
4. An FGF-7 production promoter comprising a cyclic peroxide represented by the following chemical formula (1) or a salt thereof:
5. The agent according to claim 1 or 3, wherein the ozone-treated glycerin is obtained by gas-liquid contact of a glycerin solution with a gas containing ozone.
6. The agent according to claim 5, wherein the gas-liquid contact time is 1 hour or more.
7. The agent according to claim 1 or 3, wherein the ozone-treated glycerin is obtained by treating a glycerin solution with ozone until the oxidizing power calculated as an ozone concentration is 2,000 ppm or more, thereby obtaining a high-oxidizing power ozone-treated glycerin, which is obtained by diluting the resulting glycerin with an untreated glycerin solution.
8. A composition for scalp and hair, comprising the agent according to any one of claims 1 to 4.
9. The composition for scalp and hair according to claim 8, further comprising a hair-growth aid, said hair-growth aid being at least one selected from the group consisting of Swertia japonica extract, Sargassum rosa extract, Red Clover flower extract, pyrrolidinyl diaminopyrimidine oxide, acetyl tetrapeptide-3, pyridoxine hydrochloride, tocopherol acetate, diphenhydramine hydrochloride, thiosulfuric acid, pentadecanoic acid glyceride, 6-benzylaminopurine, hinokitiol, minoxidil, carpronium chloride, t-flavanone, piroctone olamine, β-glycyrrhetinic acid, isopropyl methylphenol, forskolin, sweltiamarin, and adenosine.
Citation Information
Patent Citations
Solutions comprising ozonized oil
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