Hair growth composition

Abstract

The present invention aims to provide a novel hair growth composition. The present invention is a hair growth composition comprising an aronia extract and nicotinamide mononucleotide.

Description

Technical Field

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

Background Art

[0002] Nicotinamide mononucleotide is an intermediate metabolite in the biosynthesis of coenzyme NAD

[0005] , , , , , , , ,

[0004] , . Particularly, table Japanese Patent Publication 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 and is described as being used for promoting hair growth or hair growth. Japanese Unexamined Patent Application Publication No. 2016-135750 (Patent Document 3) describes a scalp hair cosmetic containing nicotinamide mononucleotide and having little irritation to the skin.

Prior Art Documents

Patent Documents

[0003]

Patent Document 1

Patent Document 2

Patent Document 3

Summary of the Invention

Problems to be Solved by the Invention

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

Means for Solving the Problems

[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] A hair growth composition described in [1] or [2], which is an external preparation. [Effects of the Invention]

[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 regeneration can be obtained. [Brief explanation of the drawing]

[0007] [Figure 1] This figure shows the captured data from Test Example 1. [Figure 2] This figure shows the calculation results of the hair percentage in Test Example 1. [Figure 3] This figure shows the measurement results of hair density in Test Example 2. [Figure 4] This figure shows the average percentage increase in hair density for groups 1 and 2 in Test Example 2. [Modes for carrying out the invention]

[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 N2O8P is also known 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 the present disclosure, "liposome formation" refers to the production of liposomes encapsulating the target component. In liposome formation, the target component is mixed with any lipid that serves as the membrane material of the liposome (for example, phospholipids, cholesterol sugars, fatty acids, etc.), and liposomes encapsulating the target component are formed. In the present disclosure, liposome formation may be carried out by known methods. As such a known method, for example, the liposome-formed NMN of the present disclosure can be prepared by stirring and mixing at least a liposome raw material obtained by mixing NMN, lecithin, and sugar alcohol. Known components that can be formulated in the field of liposomes may be further formulated in the raw materials for liposome formation. Also, liposome-formed NMN can be produced using commercially available lipofilms.

[0016] In the present disclosure, liposome-formed NMN is also referred to as "liposome-formed NMN".

[0017] The particle size of liposome-formed NMN is not limited, but the average particle size may be 10 - 10000 nm, may be 10 - 1000 nm, or may be 50 - 500 nm. In the present disclosure, "particle size" means the diameter of the particles measured by dynamic light scattering.

[0018] There are two types of optical isomers, α and β, in NMN, but in the present disclosure, β-NMN (CAS number: 1094 - 61 - 7) is used. The structure of β-NMN is shown below.

[0019]

Chemical formula

[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] Chemical synthesis methods for β-NMN include, for example, reacting nicotinamide with L-ribose tetraacetate and phosphorylating the resulting nicotinamide mononucleoside to produce β-NMN. 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 make up 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 pharmacokinetically acceptable 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-related ingredients> This hair growth composition may contain, in addition to aronia extract and NMN or liposomal NMN, known hair growth-related ingredients. Known hair growth-related 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; and oil-soluble solvents such as liquid oils like diethyl sebacate, diisopropyl adipate, and tri(caprylic / capric acid)glycerin. Examples of water-soluble bases or carriers include macrogols (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 or more of these bases or carriers selected from these bases or carriers.

[0028] <Other ingredients> This hair growth composition may further contain at least one component 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] <Application> This hair growth composition is suitable for hair growth applications. In this disclosure, such hair growth applications may be medical applications or non-medical applications (e.g., cosmetic purposes, maintaining or improving health, etc.). More specific examples of hair growth applications include, for example, at least one application 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 to> The target animals for this hair growth composition are mammals, 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 animals may be humans. The target animals 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] The application sites for this hair growth composition, in the case of a topical preparation, may be areas where hair is present, areas where hair was present, or areas where hair normally exists. Examples include the scalp, eyebrows, eyelids (where eyelashes grow), chin, around the mouth, and chest. Preferably, the application sites are the scalp, eyebrows, or eyelids, and more preferably the scalp. Specific application sites on the scalp include, for example, 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 a topical 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 50g, 0.1 to 20g, or 0.1 to 10g) to the above-mentioned area, for example, once 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 will result in a 10cm reduction. 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 may be in the form of a manufacturing preparation for, for example, a pharmaceutical, quasi-drug, cosmetic, or food product. Here, "manufacturing preparation" refers to any composition used in the manufacture of a pharmaceutical, quasi-drug, cosmetic, or food product, and the intended use, type, etc., of the preparation are not particularly limited.

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

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

[0040] <Manufacturing method> This hair growth composition can be manufactured by mixing aronia extract and NMN or liposomal NMN with other ingredients as needed. Mixing and other manufacturing processes can be carried out using known methods used in pharmaceuticals, quasi-drugs, cosmetics, or food products. [Examples]

[0041] [Example Test 1: Verification of Hair Growth Effect in Mice] <Test Procedure> (1) Ten C3H / HeNcrl mice (24 weeks old, male, Jackson Laboratories Japan) were prepared, and three mice that developed areas of poor hair growth during three preliminary tests were selected as subjects for the main test, and the following main test was conducted. The C3H / HeNcrl mouse is a strain that has a more clearly defined hair growth cycle than other strains.

[0042] (2) Three test mice (Mouse 1, Mouse 2, Mouse 3) had specific areas of their backs shaved with small clippers, then had their hair removed with a hair removal cream (product name: Epilat Hair Removal Cream, manufactured by Kracie Home Products Co., Ltd.), and were kept in the same condition for 24 hours.

[0043] (3) The day of hair removal was designated as day 0. From 24 hours later, for 35 days, sample 1 was applied to the back of mouse 1, sample 2 to the back of mouse 2, and sample 3 to the back of mouse 3 every day. The raw materials used to prepare samples 1 to 3 are shown in Table 1 below. Sample application involved dropping 200 μL of the sample onto the back and spreading the dropped sample over the entire back with a Conlaz stick (product name: Azunol Disposable Conlaz stick). This was done daily.

[0044] (4) For mice 1-3, photographs of their backs were taken on day 7, day 14, day 21, day 28, and day 35. Figure 1 shows the photographic data.

[0045] (5) The captured photographic 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 ratio of the area where hair growth was confirmed to the total area of ​​the head. Figure 2 shows the calculation results.

[0046] [Table 1]

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

[0048] Sample 3 was prepared in a cleanroom by adding polyoxylauryl ether as a surfactant to physiological saline, dispersing a lipid film in the solution, adding NMN to a concentration of 0.5%, and encapsulating the NMN within liposomes to produce 0.5% liposomal NMN-70H. Then, aronia powder (manufactured by Kyoto Grain System Co., Ltd.) was added to this solution to a concentration of 5 mg / ml, and the supernatant obtained by centrifugation was designated as Sample 3. In Sample 3, the average particle size of 0.5% liposomal NMN-70H was 100 nm.

[0049] <Test Results> From the images taken, on day 0, the hairless back areas of all mice (1-3) appeared pink, clearly contrasting with the areas where hair remained. 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, mouse 3 showed widespread hair growth compared to mice 1 and 2.

[0050] [Example Test 2. Verification of Hair Growth Effects 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 study, 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 temples, and back of the head, with 4 pumps (0.5 ml per pump, 2 ml total) of the sample applied to each area. After application, the subjects were instructed to gently rub it in with their fingertips. Two of the 16 subjects discontinued the study due to haircuts during the study period. (3) Under the supervision of a physician, a nurse took photographs of a total of four specific locations on each subject before the start of the study and 10 weeks later to check the condition of their 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. An area was classified as having hair if even one hair was found, and as having no hair if no hair was found. Figure 3 shows the measurement results. (5) The 14 subjects (subjects A to N) were divided into two groups: Group 1, whose hair density was 90% or higher before the start of the study, and Group 2, whose hair density was less than 90% before the start of the study. For each group, the average rate of 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, in 13 out of 14 subjects, hair density increased 10 weeks after the start of the study compared to before the study began.

[0052] As shown in Figure 4, the results 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 higher before the start of the test.< / nmn>

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 liposome-encapsulated.

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

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