Hair growth composition

Abstract

The purpose of the present invention is to provide a novel hair growth composition. The present invention is a hair growth composition that includes an extract of Aronia, and nicotinamide mononucleotide.

Description

Hair growth composition

[0001] The present invention relates to a hair growth composition.

[0002] Nicotinamide mononucleotide is an intermediate metabolite in the biosynthesis of coenzyme NAD ＋ Japanese Patent Application Laid-Open No. 2023-517413 (Patent Document 1) describes a hair care composition containing nicotinamide mononucleotide. International Publication No. 2019 / 78177 (Patent Document 2) describes a cosmetic composition containing nicotinamide mononucleotide, which is described as being used for promoting hair growth or hair growth. Japanese Patent Application Laid-Open No. 2016-135750 (Patent Document 3) describes a scalp hair cosmetic containing nicotinamide mononucleotide and having little irritation to the skin.

[0003] Japanese Patent Application Laid-Open No. 2023-517413 International Publication No. 2019 / 7817 Japanese Patent Application Laid-Open No. 2016-135750

[0004] An object of the present invention is to provide a novel hair growth composition.

[0005] The present invention includes the following. [1] A hair growth composition containing an extract of Aronia and nicotinamide mononucleotide. [2] The hair growth composition according to [1], wherein the nicotinamide mononucleotide is liposome-encapsulated. [3] The hair growth composition according to [1] or [2], which is an external preparation.

[0006] According to the hair growth composition of the present invention, at least one effect selected from the group consisting of prevention or improvement of thinning hair, improvement of hair volume, promotion of hair growth, and promotion of hair growth can be obtained.

[0007] It is a diagram showing the shooting data in Test Example 1. It is a diagram showing the calculation result of the hair growth rate in Test Example 1.It is a diagram showing the measurement result of hair density in Test Example 2. It is a diagram showing the average value of the increase rate of hair density of Groups 1 and 2 in Test Example 2.

[0008] [Hair Growth Composition] The hair growth composition of the present invention (hereinafter also referred to as "this hair growth composition") contains an extract of aronia and nicotinamide mononucleotide. The nicotinamide mononucleotide is preferably liposome-encapsulated.

[0009] In this disclosure, nicotinamide mononucleotide (chemical formula: C) １１ H １５ N ２ O ８ P) is also referred to as "NMN".

[0010] <Aronia Extract> Aronia is a plant belonging to the genus Aronia in the family Rosaceae, and is preferably selected from one or more species of Aronia albutifolia, Aronia melanocarpa, and Aronia purnifolia. The extract referred to here includes the pressed product obtained by pressing the plant as is, the plant extract itself, and the plant extract-derived product. As the plant extract, any of the following can be used: the press effluent, steam distillate, distillate, or solvent extract. The plant extract-derived product includes fractions obtained by fractionating and purifying the plant extract, and the solvent-removed product of the purified product.

[0011] For solvent extraction, polar solvents are preferred. Examples of preferred solvents include water, alcohols such as ethanol and isopropanol, esters such as ethyl acetate, and ketones such as acetone and methyl ethyl ketone. Among these, aqueous solutions containing ethanol are particularly preferred. The ethanol content is preferably 50% to 95% by mass, and more preferably 60% to 90% by mass, relative to the total amount of solvent. Extraction is performed by adding 1 to 10 parts by mass of solvent to 1 part by mass of plant material or its dried product, and immersing for several days at room temperature or for several hours at temperatures near the boiling point. If necessary, insoluble matter may be filtered out. Concentration can be performed by distillation under reduced pressure.

[0012] There are no particular limitations on the plant parts used to prepare the aronia extract; the whole plant can be used. However, it is also possible to use only specific parts such as the plant body, above-ground parts, rhizomes, trunks, leaves, stems, flower spikes, flower buds, and fruits. Preferably, the fruit is used. As for the aronia extract, it is particularly preferable to use the juice obtained by directly pressing the fruit, from the viewpoint of effectively utilizing the active ingredients.

[0013] Aronia extract can be prepared and used as described above, or you can purchase a commercially available product and use that.

[0014] In this hair growth composition, the content of aronia extract is not limited, but for example, if the total amount of this hair growth composition is 100 parts by mass, it may be 0.01 to 20 parts by mass, 0.05 to 18 parts by mass, or 0.1 to 15 parts by mass.

[0015] <NMN> In this disclosure, "liposomalization" means the production of liposomes containing the target component. In liposomalization, the target component is mixed with any lipid (e.g., phospholipids, cholesterol sugars, fatty acids, etc.) that will serve as the membrane material for the liposome, thereby forming liposomes containing the target component. In this disclosure, liposomalization may be carried out by known methods. As an example of such a known method, the liposomal NMN of this disclosure can be prepared by stirring and mixing a liposome raw material obtained by mixing at least NMN, lecithin, and sugar alcohol. The raw material for liposomalization may further contain known components that can be incorporated in the field of liposomes. In addition, liposomal NMN can also be produced using commercially available lipofilms.

[0016] In this disclosure, liposomal NMN is also referred to as "liposomal NMN."

[0017] The particle size of liposomal NMN is not limited, but may have an average particle size of 10 to 10,000 nm, 10 to 1,000 nm, or 50 to 500 nm. In this disclosure, "particle size" means the diameter of the particle as measured by dynamic light scattering.

[0018] NMN exists as two optical isomers, α and β, but in this disclosure, β-NMN (CAS number: 1094-61-7) is used. The structure of β-NMN is shown below.

[0019]

[0020] β-NMN can be prepared by any method. For example, purified β-NMN artificially synthesized by chemical synthesis, enzymatic methods, fermentation, etc., can be used. Furthermore, since β-NMN is a component widely present in living organisms, β-NMN obtained by extraction and purification from natural raw materials such as animals, plants, and microorganisms can also be used. Commercially available purified β-NMN may also be used.

[0021] β-NMN can be synthesized chemically by, for example, reacting nicotinamide with L-ribose tetraacetate and phosphorylating the resulting nicotinamide mononucleoside. Enzymatic methods include, for example, producing β-NMN from nicotinamide and 5'-phosphoribosyl-1'-pyrophosphate (PRPP) using nicotinamide phosphoribosyltransferase (NAMPT). Fermentation methods include, for example, producing β-NMN from nicotinamide using the metabolic pathway of microorganisms expressing NAMPT.

[0022] The NMN or liposomal NMN contained in this hair growth composition may be a pharmacologically acceptable salt of β-NMN. The pharmacologically acceptable salt of β-NMN may be an inorganic salt or an organic salt having a basic moiety such as an amine. Examples of acids that constitute such salts include acetic acid, benzenesulfonic acid, benzoic acid, camphorsulfonic acid, citric acid, ethensulfonic acid, fumaric acid, gluconic acid, glutamic acid, hydrobromic acid, hydrochloric acid, isethionic acid, lactic acid, maleic acid, malic acid, mandelic acid, methanesulfonic acid, mucinic acid, nitric acid, pamoic acid, pantothenic acid, phosphoric acid, succinic acid, sulfuric acid, tartaric acid, and p-toluenesulfonic acid. Furthermore, the pharmacologically acceptable salt of β-NMN may be an alkali salt or an organic salt having an acidic moiety such as a carboxylic acid. Examples of bases that constitute such salts include alkali metal salts or alkaline earth metal salts derived from bases such as sodium hydride, potassium hydroxide, calcium hydroxide, aluminum hydroxide, lithium hydroxide, magnesium hydroxide, zinc hydroxide, ammonia, trimethylammonia, triethylammonia, ethylenediamine, lysine, arginine, ornithine, choline, N,N'-dibenzylethylenediamine, chloroprocaine, procaine, diethanolamine, N-benzylphenethylamine, diethylamine, piperazine, tris(hydroxymethyl)-aminomethane, and tetramethylammonium hydroxide.

[0023] The NMN or liposomal NMN contained in this hair growth composition may be free β-NMN or a solvate of a pharmacoposityal salt of β-NMN. Examples of solvents that form the solvate include water and ethanol.

[0024] The amount of NMN contained in this hair growth composition as NMN or liposomal NMN is not limited, but for example, if the total amount of this hair growth composition is 100 parts by mass, it may be 0.01 to 20 parts by mass, 0.05 to 18 parts by mass, or 0.1 to 15 parts by mass.

[0025] <Other Hair Growth Ingredients> This hair growth composition may contain known hair growth ingredients in addition to aronia extract and NMN or liposomal NMN. Known hair growth ingredients may include at least one selected from the group consisting of minoxidil, finasteride, dutasteride, carpronium chloride, bimatoprost, trans-3,4'-dimethyl-3-hydroxyflavanone (t-flavanone), 6-benzylaminopurine (cytoprin), glyceride pentadecanoate (pentadecane), adenosine, panthenol (D-pantothenyl alcohol), pantothenyl ethyl ether, DL-α-tocopherol acetate, dipotassium glycyrrhizate, carrot extract, Swertia japonica extract, Scutellaria baicalensis extract, and Ginkgo biloba extract.

[0026] In addition to the hair growth-related ingredients mentioned above, this hair growth composition may also contain at least one ingredient selected from the group consisting of, for example, blood circulation promoters, angiogenesis promoters, keratolytic agents, cell activators, and anti-inflammatory agents.

[0027] <Base or Carrier> This hair growth composition may contain a base or carrier. Examples of bases or carriers include oil-soluble bases or carriers such as petrolatum, refined petrolatum, paraffin, liquid paraffin, lanolin, refined lanolin, hydrocarbons, vegetable oils, animal oils and other fatty oils; higher alcohols; Plastibase; glycols; higher fatty acids; oil-soluble solvents such as liquid oils such as diethyl sebacate, diisopropyl adipate, and tri(caprylic / capric acid)glycerin; and water-soluble bases or carriers such as macrogol (polyethylene glycols) such as macrogol 200, macrogol 400, macrogol 1500, macrogol 1540, macrogol 4000, and macrogol 20000; polyhydric alcohols such as concentrated glycerin and propylene glycol; water-soluble polymers such as povidone, polyvinyl alcohol, and polyvinylpyrrolidone; alcohols such as ethanol and isopropyl alcohol; and water. The topical preparation of the present invention may use any one of these bases or carriers, either individually or in combination of two or more.

[0028] <Other Ingredients> This hair growth composition may further contain at least one ingredient selected from the group consisting of, for example, enzymes, plant and animal extracts, amino acids, vitamins, humectants (such as heparinoids), antioxidants, surfactants, UV protection agents, bactericides, anti-seborrheic agents, transdermal absorption enhancers, thickeners, dispersants, cooling agents, fragrances, surfactants, pH adjusters, excipients, solvents, preservatives, antiseptics, emulsifiers, chelating agents, coloring pigments, and colorants.

[0029] <Uses> This hair growth composition is suitable for hair growth purposes. In this disclosure, such hair growth purposes may be medical or non-medical (e.g., cosmetic purposes, maintaining or improving health, etc.). More specific examples of hair growth purposes include, for example, at least one selected from the group consisting of prevention or improvement of thinning hair, prevention or improvement of hair loss, improvement of hair volume, improvement of hair density, improvement of hair growth rate, improvement of hair quality (e.g., improvement of hair firmness or elasticity, improvement of eyelash shine), promotion of hair growth, and promotion of hair growth. Hair targeted for hair growth with this hair growth composition includes hair, eyelashes, eyebrows, etc.

[0030] <Applicable Subjects> This hair growth composition is applicable to mammals, for example, and more specifically, humans, equids (e.g., horses, donkeys, zebras, etc.), livestock (e.g., cattle, sheep, goats, pigs, etc.), pet animals (e.g., cats, dogs, rabbits, hamsters, etc.), and laboratory animals (rats, primates, mice, etc.). The target subject may be humans. The target subject may be non-human mammals, including but not limited to dogs, cats, cattle, horses, pigs, donkeys, goats, camels, mice, rats, guinea pigs, sheep, llamas, monkeys, gorillas, or chimpanzees.

[0031] In the case of a topical preparation, the application site of this hair growth composition may be the area where hair is present, where hair was previously present, or where hair normally exists. Examples include the scalp, eyebrows, eyelids (where eyelashes grow), chin, around the mouth, and chest. Preferably, the application site is the scalp, eyebrows, or eyelids, and more preferably the scalp. Specific application sites on the scalp include the crown of the head, the hairline (e.g., the hairline on the forehead), and the hair part.

[0032] <Form of Composition> In one form (hereinafter also referred to as "Form 1"), this hair growth composition may be in the form of a pharmaceutical, quasi-drug, cosmetic, or food. It is preferable that it be used as a topical preparation in the form of a pharmaceutical, quasi-drug, cosmetic, or a formulation thereof.

[0033] Specific examples of topical preparations include, for example, hair growth stimulants, hair tonics, hair lotions, hair dyes, hair manicures, shampoos, conditioners, rinses, treatments, perming agents, styling products, hair sprays, scalp packs, hair masks, scalp massage agents, eyeliners, mascaras, eyeshadows, eyebrow pencils, and other topical pharmaceuticals, quasi-drugs, or cosmetics. Dosage forms of topical preparations include, for example, topical solid preparations, topical liquid preparations, sprays, ointments, creams, gels, and patches.

[0034] In the form of an external preparation, the content of aronia extract and the content of NMN or liposomal NMN in this hair growth composition may be, for example, 0.01 to 20 parts by mass, 0.05 to 18 parts by mass, or 0.1 to 15 parts by mass, relative to the total amount of the composition.

[0035] In the form of a topical preparation, this hair growth composition may be appropriately modified depending on the disease, symptoms, health condition or aesthetic condition to which it is applied, as well as the age and sex of the subject. For example, it can be administered by applying an appropriate amount (for example, about 0.05 to 50 g, 0.1 to 20 g, or 0.1 to 10 g) to the above-mentioned area, one to several times a day (for example, about 1 to 5 times, preferably 1 to 3 times).

[0036] In the form of a topical preparation, the application of this hair growth composition for 10 cm ２ The single dose may also be adjusted as appropriate depending on the disease, symptoms, health condition or aesthetic condition, as well as the age and sex of the subject. For example, the amount of aronia extract and NMN may be 0.01 to 20 mg, 0.05 to 18 mg, or 0.1 to 15 mg.

[0037] In another form (hereinafter, also referred to as "Form 2"), the hair growth composition can be in the form of a formulation for the production of, for example, pharmaceuticals, quasi-drugs, cosmetics or foods. Here, the formulation for production represents the entire composition used in the production of pharmaceuticals, quasi-drugs, cosmetics or foods, and the purpose of use, type, etc. of the formulation are not particularly limited.

[0038] Form 2 can be used as the material of Form 1. Therefore, in Form 2 obtained by using this, it is preferable that Form 2 contains each component so that the content of the extract of aronia and the content of NMN contained as NMN or liposomal NMN are as described above.

[0039] In Form 2, the hair growth composition may further contain components that can be used in the above Form 1. In Form 2, the hair growth composition may further contain, for example, excipients, emulsifiers or both of them.

[0040] <Manufacturing method> The hair growth composition can be manufactured by mixing an extract of aronia and NMN or liposomal NMN with other components as necessary. For mixing and other manufacturing steps, known means used in pharmaceuticals, quasi-drugs, cosmetics or foods can be used.

[0041] [Test Example 1. Verification of hair growth effect by mice] <Test procedure> (1) Ten C3H / HeNcr1 mice (24 weeks old, male, Jackson Laboratories Japan) were prepared, and three mice with areas where hair growth was difficult during three preliminary tests were selected as the subjects of this test, and the following main test was conducted. C3H / HeNcr1 mice are a strain with a clearer hair growth cycle than other strains.

[0042] (2) After shaving the specific area on the back of three test mice (Mouse 1, Mouse 2, Mouse 3) with a small clipper, depilation was performed with a depilatory cream (product name: Epilat depilatory cream, manufactured by Kracie Home Products Co., Ltd.), and they were kept in the same state for 24 hours.

[0043] (3) Using the day of hair removal as day 0, from 24 hours later for 35 days, every day, Sample 1 was applied to the back of Mouse 1, Sample 2 was applied to the back of Mouse 2, and Sample 3 was applied to the back of Mouse 3. The raw materials used for the preparation of Samples 1 to 3 were as shown in Table 1 below. For the application of the samples, 200 μL of the sample was dropped onto the back, and the dropped sample was spread over the entire back using a conrage stick (product name: Asunoal Dispo Conrage Stick). This was done every day.

[0044] (4) For Mice 1 to 3, photos of the back were taken on the 7th day (day 7), 14th day (day 14), 21st day (day 21), 28th day (day 28), and 35th day (day 35). Figure 1 shows the photographed data.

[0045] (5) The photographed photo data was observed using an all-in-one microscope (product name: BZ-X810, manufactured by Keyence Corporation), and the hair growth rate was calculated. The hair growth rate was defined as the area ratio of the region where hair growth was confirmed to the area of the entire head. Figure 2 shows the calculation results.

[0046]

[0047] Sample 2 was prepared by dissolving NMN (manufactured by Oriental Yeast Co., Ltd.) in physiological saline at a concentration of 5 mg / ml.

[0048] Sample 3 was prepared by adding polyoxy lauryl ether as a surfactant to physiological saline in a clean room, dispersing a lipid film therein, adding NMN to a concentration of 0.5%, encapsulating NMN in liposomes, and manufacturing 0.5% liposomalized NMN-70H in the clean room. Then, the supernatant obtained by centrifuging the solution obtained by adding aronia powder (manufactured by Kyoto Grain Systems Co., Ltd.) at a concentration of 5 mg / ml was used as Sample 3. In Sample 3, the average particle size of 0.5% liposomalized NMN-70H was 100 nm.

[0049] <Test Results> From the images taken, on day 0, the hairless back areas of all mice (Mice 1-3) appeared pink, and the difference from the areas with remaining hair was clear. On day 14, hair growth began to be observed overall in Mice 1-3, but no hair growth was observed in some areas where hair growth was difficult in all mice. With continued application, on day 28, Mice 3 showed hair growth over a wider area compared to Mice 1 and 2.

[0050] [Test Example 2. Verification of Hair Growth Effect in Humans] <Test Procedure> (1) Sixteen healthy male and female volunteers in their 70s (without diabetes or other related diseases) were used as subjects. (2) For 10 weeks from the start of the test, the 16 subjects applied the same sample as Sample 3 in Test Example 1 above to specific areas once a day. The specific areas were the forehead, left and right sides of the head, and back of the head, for a total of four areas. Four pumps (0.5 ml per pump, 2 ml total) of the sample were applied to each area. After application, the sample was gently rubbed in with the fingertips. Two of the 16 subjects discontinued the test due to haircuts during the test period. (3) Under the supervision of a physician, a nurse took photographs of the four specific areas of each subject before the start of the test and after 10 weeks to check the condition of the skin. (4) Photographs taken of 14 subjects (subjects A to N) were observed using an all-in-one microscope (product name: BZ-X810, manufactured by Keyence Corporation) and hair density was calculated. Hair density was determined by identifying whether the area of ​​the head had hair or not, and then calculating the ratio of the area of ​​the hair-containing area to the total head area. If even one hair was found, it was identified as an area with hair, and if no hair was found, it was identified as an area without hair. Figure 3 shows the measurement results. (5) The 14 subjects (subjects A to N) were divided into two groups: Group 1, whose hair density before the start of the study was 90% or more, and Group 2, whose hair density before the start of the study was less than 90%. For each group, the average increase in hair density from before the start of the study to 10 weeks after the start of the study was calculated. Subjects C, D, E, F, J, K, and L belonged to Group 1, and subjects A, B, G, H, I, M, and N belonged to Group 2. Figure 4 shows the calculation results.

[0051] <Test Results> As shown in Figure 3, it was confirmed that hair density increased 10 weeks after the start of the test in 13 out of 14 subjects compared to before the start of the test.

[0052] As shown in Figure 4, it was confirmed that Group 1, whose hair density was less than 90% before the start of the test, experienced a significantly greater increase in hair density after sample application than Group 2, whose hair density was 90% or more before the start of the test.

Claims

1. A hair growth composition comprising aronia extract and nicotinamide mononucleotide.

2. The hair growth composition according to claim 1, wherein the nicotinamide mononucleotide is liposomal.

3. A hair growth composition according to claim 1 or 2, which is an external preparation.

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