JPH0238565B2 - - Google Patents

Description

[Detailed description of the invention]

<Industrial Application Field> The present invention relates to a novel hair nourishing and hair growing agent that has no side effects and has remarkable hair nourishing and hair growing effects. <Prior Art> There are many unknown aspects of the medical science related to hair loss and hair growth, and there are many unknown points regarding the physiological mechanisms of action of hair nourishing ingredients used for this purpose. At present, causes of hair loss are considered to include endocrine abnormalities, hair cycle abnormalities, autonomic nervous system disorders, poor blood circulation, nutritional disorders, and others (genetics, aging, etc.). Conventional hair tonic ingredients include hormones such as follicle hormone (Japanese Patent Application Laid-Open No. 60-38313), vitamin E,
B ₂ , B ₆ , biotin, vitamins such as pantothenic acid, and other amino acids (peptide substances:
Japanese Patent Publication No. 61-7209), herbal medicine extracts such as Oriental japonica extract, anti-inflammatory agents such as diphenhydramine hydrochloride, keratolytic agents such as Photosensor No. 301, hinokiol, lactic acid, etc.
There are humectants such as glycerin, other scalp irritants, disinfectants, and cooling agents. In addition, among the plants of the Lamiaceae family, especially Hikiokoshi (Isodon japonicus),
H _ARA ), Isodon
trichocarpus K _UDO ), Isodon
There are precedents for the use of extracts (crystalline substances) in water or organic solvents of plants belonging to the genus Isodon, such as Kameda O _KUYAMA ), in hair-growth cosmetics. (Special Publication No. 38-8500, Special Publication No. 41-2197) Hair nourishing and hair growth agents are used with the expectation of local efficacy by combining the above-mentioned hair nourishing ingredients alone or in combination. It promotes hair growth, prevents dandruff, itchiness, and inflammation, and prevents thinning hair and hair loss, with the aim of achieving comprehensive hair growth and growth effects. Recently, there has been a tendency to focus on the properties of substances, such as their ability to inhibit testosterone-5α-reductase and to activate cells and skin, and to use these substances as hair nourishing agents. According to one theory, the reason why the above-mentioned testosterone-5α-reductase inhibitor is used as a hair growth agent is to treat male-pattern baldness, coarse hair, acne vulgaris,
Physiological symptoms such as seborrhea are thought to be caused by increased stimulation of androgens caused by excessive accumulation of androgen (5α-dihydrotestosterone) in the vicarious ejaculatory system. In other words, this male hormone (5α-dihydrotestosterone)
is produced by reducing testosterone by the action of testosterone-5α-reductase. It is believed that the male hormone is produced and accumulated in various organs such as hair roots and sebaceous glands under the action of testosterone-5α-reductase, resulting in atrophy of hair roots and inducing hair loss and baldness. For example, examples of substances that have testosterone-5α-reductase inhibiting properties include bicyclic fused ring compounds such as bicyclic terpenes (described later), carboxylic acids such as higher fatty acids (Japanese Patent Application Laid-Open No. 59-152308, No. 59-172410, JP-A No. 59-172411, JP-A No. 61
-5007, JP-A-61-5014, JP-A-61-7205, etc.), aromatic alcohols, aromatic carboxylic acids (JP-A-57-53401, etc.), and other natural extracts [e.g., testosterone- Examples of 5α-reductase inhibitors that exist in the natural world include Acacia japonica, Ukiyo, Kengoshi, Gobaishi, Shiyakuyaku, Syazenshi, Senso, Rhubarb, Chiyoji,
Solvent extracts of herbal medicines of betel nut, rosin, katsuko thistle, gennosyouko, kagosou, saiko, inchin, eijitsu, yokuinin, soybean, bittern, japonica, japonica, valerian and valerian (Japanese Patent Application Laid-open No. 146829/1982)], and compounds (special (Japanese Patent Publication No. 59-59606, Japanese Patent Application Publication No. 59-59607, etc.). Examples of bicyclic fused ring compounds (examples of bicyclic terpene derivatives) having enzyme inhibiting properties include:
5,6-dimethyl-8-isopropenyl-bicyclo[4,4,0]decen-1-one-3 (JP-A-Sho
59-53417), 4,8-dimethyl-2-isopropylidene-1,2,3a, 4,5,6-hexahydro-azulenone (6) or 3,6,8,-tetramethyl-1,2, 4,7,8,8a-hexahydro-azulenone (JP-A No. 59-53418, JP-A No. 59-59)
-55813), 4-methyl-1-isopropyl-bicyclo[3,1,0]hexen-3-one 2 and 4,6,6-trimethyl-bicyclo[3,1,
1] Heptene-3-one-2 (JP-A-59-53419
No. 59-55812). Thus, the reason why there is a wide range and variety of substances that are said to have testosterone-5α-reductase inhibitory properties and/or hair-growth/hair-growth effects is due to the enzymatic activity of the testosterone-5α-reductase and the hair-growth/hair-growth effects. The specificity of physiological activity related to hair growth etc. is thought to be due to the correlation with the molecular structure of the chemical substance. Even if the chemically similar compounds are the same or homologous, the presence or absence and potency of the enzymatic activity and physiological activity vary greatly depending on the isomer (positional isomer, structural isomer, geometric isomer). Therefore, it is extremely difficult to predict the presence or absence and magnitude of the properties related to the enzyme activity and physiological activity. In particular, the physiological activities of various substances, such as their hair-nurturing and hair-growth properties, differ significantly in their specificity, and it is currently impossible to distinguish between them unless the hair-nurturing and hair-growth effects of each substance are directly measured and searched one by one. Thus, there are a wide variety of substances that have hair nourishing and hair growing effects, and these conventional hair nourishing and hair growing agents (particularly hormones) may have side effects.
Furthermore, the hair nourishing and hair growing effects are not necessarily sufficient, and the development of new hair nourishing and hair growing agents is desired. By the way, it is preferable that the active ingredients having various effects (for example, hair nourishing/hair growing effects) are originally specified as substances. Various effects of extracts derived from natural products such as crude drugs or medicinal plants (hair nourishing/growth effects, etc.)
When determining the presence or absence of hair growth, it is necessary to determine which active ingredients in the extract produce the desired effect (hair growth/growth effect, etc.), and whether the effect (hair growth/hair growth effect, etc.) is achieved only through the synergistic action of two or more active ingredients. It must be said that it is extremely important to elucidate whether or not the product has the desired effect (e.g., effectiveness, etc.). In particular, it is a well-known fact that the active ingredients contained in crude drugs and medicinal plants are completely different depending on the "family", "genus", "species", and "subspecies" to which the raw material plants belong. Temporarily, the above “department”,
Even if plants are the same in terms of "genus", "species", etc. (they are simply variants of each other), there may be differences in the production areas of the plants, or differences between cultivated species and wild species. It is also a well-known fact that the types and contents of active ingredients contained in plants are completely different. Therefore, from this point of view, there has been a strong desire to identify substances that have hair-nurturing and hair-growth effects among compounds that exist in the natural world. <Problems to be Solved by the Invention> This invention is intended to meet the above requirements, and as a result of searching and testing the hair-nurturing and hair-growth effects of terpenes and their derivatives, it was discovered that monocyclic monoterpene ketones This product was developed based on the discovery that piperitenone, isopiperitenone, and carvone have excellent hair-nourishing and hair-growth effects, thereby providing a hair-nourishing and hair-growth agent that is safe and has no side effects and has remarkable hair-nourishing and hair-growth effects. The purpose is to <Means for Solving the Problems> In order to achieve the above object, the present invention uses piperitenone (IUPAC name: 1,4(8)-paramentadiene-3) as an active ingredient of a hair growth agent. -on) (hereinafter referred to as "piperitenone"), isopiperitenone (isopiperitenone,
IUPAC name: 1,8-paramentadien-3-one) (hereinafter referred to as "isopiperitenone"), carvone (IUPAC name: 5,8-paramentadien-2-one) (hereinafter referred to as "carvone")
At least one of the three types of monoterpene ketones is contained as an active ingredient. By the way, in the natural world, for example, the piperitenone is found in Mentha pulegium L.var. of the Lamiaceae family.
eriantha), and a variety of the pennyroyal hatsuka (Mentha
present in the essential oil of L. var. villona Benth. In nature, isopiperitenone is present in the essential oils of Mentha pulegium L. var. eriantha and Mentha rotundifolia varieties of the Lamiaceae family. Piperitenone and isopiperitenone are both contained in the essential oil ("pennyroyal oil") of the above-mentioned pennyroyal oil, and are isolated and purified by a known method described below. Further, the carvone has optical isomers of d-form and l-form. And the d-isomer carvone is
In nature, Carum is a member of the Umbelliferae family.
It is present in the essential oil of the seeds of Anethum graveolens (carvi L.) and anethum oil. on the other hand,
L-carvone can be found in various spearmints (Menthaspicate), for example, Mentha in the Lamiaceae family.
Present in the essential oil of viridis L. (spearmint oil). The piperitenone, isopiperitenone, and carvone are obtained by adding a sodium sulfite (Na ₂ SO ₃ ) solution to the various essential oils and shaking them on a hot bath to add and dissolve them and separate the oil layer and the aqueous layer. It can be prepared by applying a caustic soda aqueous solution to the part and regenerating and separating it. In addition, the identity of each compound and its purity can be confirmed by measuring the physical constants of the prepared piperitenone, isopiperitenone, and carvone. Of course, any of the piperitenone, isopiperitenone, and carvone can be chemically synthesized by known methods, and the chemically synthesized piperitenone, isopiperitenone, and carvone can be used as the hair growth agent according to the present invention. Needless to say. Moreover, as mentioned above, the raw material plants for the piperitenone and isopiperitenone, which are the active ingredients of the hair nourishing/growth agent of this invention, belong to the genus Mentha of the Labiatae family, as mentioned above. On the other hand, the raw material plants (Hikiokoshi, Black Banana Hikiokoshi, and Camellia Hikiokoshi) according to the above documents (Japanese Patent Publication Nos. 38-8500 and 41-2197) are plants belonging to the ``genus Isodon'' of the ``Lamiaceae'' family. The "genus" to which the raw material plants of both the raw material plants according to the above and the raw material plants described in the above-mentioned literature belong are completely different. On the other hand, there is no literature that states that plants belonging to the ``Isodon genus'' (Hikiokoshi, Black Banana kiokoshi, Camellia chinensis) contain piperitenone and isopiperitenone. Furthermore, the raw material plant for the carvone used as the active ingredient of the hair nourishing/hair growth agent according to the present invention (Prunus japonicus) belongs to the ``genus Carum'' of the ``Umbelliferae''; −146829)
One of the raw material plants for this, ``Foeniculum'', belongs to the ``genus Foeniculum'' in the ``Umbelliferae'' family, and the genus to which ``Foeniculum'' belongs is completely different from the genus to which ``Foeniculum'' belongs. In addition, while the main component of the essential oil (caraway oil) is "carvone," the main component of the essential oil (sweet) of the fenugreek is anethole, etc. It is clear from the literature that carvone is not contained in oil (sweet oil). （Analysis of
Essentia Oils by Gas Chromatography and
Mass Spectrometry ~ Gas chromatography
Analysis of natural fragrances using mass spectra ~p83~
85, p92-95, Yoshiro Shoda, October 1, 1975, Co., Ltd.
(Published by Hirokawa Shoten) Piperitenone, isopiperitenone, and carvone are recognized to exhibit hair nourishing and hair growth effects at a single concentration of each of them at a concentration of 0.001% or more (0.001 to 30%). This piperitenon,
The test method for the hair-nourishing and hair-growth effects of isopiperitenone and carvone is to shave the hair from the back of a domestic rabbit (10 weeks old), and apply a diluted solution of each compound at a predetermined concentration (solvent example: 99.5%) to the shaved area. It can be detected by repeatedly applying ethanol) over a certain period of time and measuring the elongated hair. In addition, piperitenone, isopiperitenone, and carvone are both nontoxic and irritating to the skin (by the Patchist method, etc.), and have no side effects such as those of hormones. The hair growth agent of the present invention is prepared by containing at least one selected from piperitenone, isopiperitenone, and carvone as an active ingredient. The amount of piperitenone, isopiperitenone and/or carvone in the hair growth agent of the present invention is not particularly limited as it can be varied depending on the form of use. In principle, it is sufficient that it exists in an effective amount, but in general, the content (single amount or combined total amount) is 0.001 to 30% by weight based on the total amount of the hair growth product as a final product. %,
Preferably 0.01 to 15% by weight (more preferably 0.1 to 10% by weight) can exhibit hair nourishing and hair growth effects. In addition, the hair growth agent of the present invention is prepared by blending at least one kind selected from the group of compounds consisting of piperitenone, isopiperitenone, and carvone into various known (cosmetic) bases by a conventional method. It can be applied to creams, milky lotions, hair liquids, hair lotions, hair rinses, hair tricks, pomades, shampoos and other cosmetics. Further, the cosmetic can be applied in various forms such as a solution, sol, gel, emulsion, ointment, oil, wax, and spray (aerosol). Furthermore, the hair growth/growth agent of this invention can be applied to other hair growth/growth agents.
It goes without saying that it can be used in combination with a hair restorer, and an excellent synergistic effect can be achieved. Furthermore, the hair growth agent of the present invention is stable against various surfactants, solvents, pigments, fragrances, preservatives, antioxidants, humectants, and other additives and various cosmetic base materials. Therefore, it can be used in combination with these various additives. <Example> Next, a description will be given based on a specific example. (1) About piperitenon. The physical constants of piperitenone used in this invention are as follows. Boiling point = 106-107°C/10mmHg, d ²⁰ ₄ = 0.977, n ²⁰ _D = 1.525 (2) Regarding isopiperitenone. The physical constants of isopiperitenone used in this invention are as follows. Boiling point = 83-86°C/2 mmHg, d ²⁵ ₂₅ = 0.964, n ²⁰ _D = 1.5054 (3) Regarding l-carvone. The physical constants of l-carvone used in this invention are as follows. Boiling point = 230-231°C, d ¹⁵ ₁₅ = 0.9652, n ²⁰ _D = 1.4998, [α] ²⁰ _D −62.46° (4) Piperitenone, isopiperitenone and l-
Test method for carvone's hair growth and hair growth effects. The hair on the back of a male rabbit (10 weeks old) was shaved.
0.2% each of piperitenone, isopiperitenone, and l-carvone once a day in this area.
1 ethanol solution (solvent: 99.5% ethanol)
Apply 1 ml each and measure the length of the elongated hair on the 6th day. As a control, 1 ml of 99.5% ethanol, which does not contain any of the above-mentioned compounds, is similarly applied to a comparatively close control position on the back once a day, and the length of the elongated hair on the 6th day is similarly measured. . The test results are shown in Table 1. In addition, in the table, A = average value ± standard deviation of the hair on the control side (mm) A′ = average value ± standard deviation (mm) of the hair on the test side B = (average value of the hair on the test example) - (average value of the hair on the control side hair average value) (mm) *=means the average of each average value of the control side and the test side, respectively. All units are mm.

A significant difference is observed in [Table].

【table】

A significant difference is observed in [Table].

A significant difference is observed in [Table].
(3) Prescription example of shampoo [Ingredients] [Content/weight%] ● Sodium polyoxyethylene alkyl ether sulfate (EO 2 mol) ...15 ● Coconut oil fatty acid diethanolamide ...5 ● Glycerin ...3 ● Piperitenone, l -Carvone or/and piperitenone...0.2 ●Fragrances and preservatives...Appropriate amount ●Ion exchange water...The total is 100. (4) Hair cream formulation example [Ingredients] [Content/weight%] ●Liquid paraffin...20 ●Solid paraffin...3 ●Polyoxyethylene cetyl ether (EO
15 moles)...2 ●Sorbitan sesquioleate...1 ●Piperitenone, l-carvone or/and isopiperitenone...0.5 ●Potassium hydroxide...0.1 ●Glycerin...3 ●Fragrances and preservatives...Appropriate amount ●Ion exchange Water: Set the total to 100. (5) Example of hair lotion formulation [Ingredients] [Content/Weight%] ●95% ethanol...20 ●Glycerin...3 ●Polyoxyethylene sorbitan monolaurate (EO 20 mol)...1 ●Piperitenone, l- Carvone or/and isopiperitenone...0.5 ●Fragrances and preservatives...Appropriate amount ●Ion-exchanged water...The total is 100. (6) Hair Tonik formulation example [Ingredients] [Content/Weight%] ●95% ethanol...60 ●Polyoxyethylene hydrogenated castor oil (EO 60
Mol)...0.5 ●Glycerin...3 ●Piperitenone, l-carvone or/and isopiperitenone...0.1 ●Fragrances and pigments...appropriate amount ●Ion-exchanged water...The total is 100. (7) Prescription example of pomade [Ingredients] [Content/weight%] ●Japanese blackberry...13 ●Castor oil...85.8 ●Piperitenone, l-carvone or/and isopiperitenone...1 ●Fragrance...0.2 <Action of the invention Effects> The hair nourishing agent of the present invention has excellent hair nourishing and hair growing effects that are safe and have excellent hair nourishing and hair growing effects due to the excellent hair nourishing and hair growing effects of piperitenone, isopiperitenone, and carvone. be effective.

Claims (1)

[Claims] 1 Among monocyclic monoterpene ketones, piperitenone and isopiperitenone (iso-
A hair nourishing agent containing as an active ingredient at least one compound selected from the compound group consisting of piperitenone and carvone.