JP7162803B2 - Composition for hair growth and/or hair restoration - Google Patents

Description

The present invention relates to hair growth and/or hair restoration compositions.

Vascular endothelial growth factor (VEGF) acts specifically on vascular endothelial cells to promote their proliferation and promote the formation of new blood vessels. By promoting the formation of new blood vessels, it is possible to treat wounds and promote hair growth and/or hair growth.

As a substance that promotes the expression of VEGF and has hair growth and/or hair growth effects, for example, sterylglucopyranoside having a structure in which a sterol residue is bound to the 3-position of a cyclopentanohydrophenanthrene ring has been proposed (Patent Reference 1).

On the other hand, plasmalogen, which is a type of phospholipid with antioxidant properties and one of glycerophospholipids, promotes neurogenesis, suppresses neuroinflammation by lipopolysaccharide (LPS), It is known to have an inhibitory effect on the accumulation of Aβ) protein, and is said to be effective against cranial nerve diseases such as Alzheimer's disease, Parkinson's disease, depression, and schizophrenia. For example, Non-Patent Document 1 reports that the memory function of mild Alzheimer's disease is improved in patients to whom scallop-derived purified plasmalogen is administered.

JP 2012-246279 A

Fujino T. et al, “Efficacy and Blood Plasmalogen Changes by Oral Administration of Plasmalogen in Patients with Mild Alzheimer's Disease and Mild Cognitive Impairment: A Multicenter, Randomized, Double-blind, Placebo-controlled Trial” EBioMedicine, [17] (2017) 199-205

An object of the present invention is to provide a composition that promotes the expression of vascular endothelial growth factor (VEGF).

As a result of intensive studies aimed at solving the above problems, the present inventors found that the expression of vascular endothelial growth factor (VEGF) can be further promoted by combining steryl glucopyranoside with plasmalogen, and thus completed the present invention. Completed.

That is, the present invention is as follows.
[1] A composition for promoting angiogenesis, comprising steryl glucopyranoside and plasmalogen.
[2] A composition for hair growth and/or hair restoration, comprising steryl glucopyranoside and plasmalogen.

（式中、Ｚは、コレステロールを示す。） [3] The composition described in [1] or [2] above, wherein the steryl glucopyranoside is a compound represented by the following general formula (I).

(In the formula, Z represents cholesterol.)

[4] The composition according to any one of [1] to [3] above, wherein the plasmalogen is derived from animal tissue.
[5] The composition according to [4] above, wherein the animal tissue is an animal tissue selected from shellfish, sea squirts and birds.

The composition of the present invention has an excellent vascular endothelial growth factor (VEGF) expression promoting effect.

FIG. 4 shows the results of VEGF expression in HDF-a cells (human fibroblasts).

The composition of the present invention is characterized by containing sterylglucopyranoside and plasmalogen.
The composition of the present invention promotes the expression (secretion) of vascular endothelial growth factor (VEGF) in human fibroblasts and the like, thereby promoting angiogenesis. Promoting angiogenesis can improve hair growth and/or hair restoration and wound healing. That is, VEGF acts on vascular endothelial cells in the scalp to increase new blood vessels and efficiently provide nutrients to hair roots, thereby promoting hair growth and/or hair restoration. In addition, VEGE acts on vascular endothelial cells at the wound site to increase new blood vessels, efficiently form granulation tissue, and improve the wound.

That is, the composition of the present invention can be used as a composition for promoting VEGF expression, a composition for promoting angiogenesis, a composition for hair growth and/or hair restoration, a composition for improving wounds, and the like. Here, hair growth in the present invention refers to the treatment of patients with alopecia to grow lost hair, and hair growth refers to the prevention of thinning hair and hair loss, to grow existing hair into strong hair. . In addition, the term "wound improvement" in the present invention refers to suppression of wound deterioration and treatment of wounds.

[steryl glucopyranoside]
The steryl glucopyranoside used in the present invention is represented by the following general formula (I).

In the general formula (I), Z is a sterol residue other than the hydroxyl group bonded to the 3-position of the cyclopentanohydrophenanthrene ring.

Examples of the sterol residue represented by Z in the general formula (I) include residues of cholesterol, β-sitosterol, stigmasterol, campesterol and bradycasterol, with cholesterol being preferred. That is, cholesteryl glucopyranoside is preferable as the steryl glucopyranoside represented by the general formula (I).
Some steryl glucopyranosides have isomers, but any isomer may be used, and the glucopyranosyl bond may be either α-isomer or β-isomer.

The steryl glucopyranoside represented by general formula (I) may be a naturally occurring substance or a synthetic product. In general, steryl glucopyranoside can be obtained by extraction from natural products such as bird feathers, or by chemical synthesis using sterol and D-glucose. Specifically, it is as follows.

<Naturally derived cholesteryl glucopyranoside>
Bird feathers are crushed and treated with a suitable extraction solvent to first extract all lipids.
Next, a methanol-water solution is taken out from this total lipid and treated with a weak alkali to obtain a complex lipid fraction stable in alkali treatment.
The obtained complex lipid fraction is subjected to silicic acid column chromatography or silicic acid thin layer chromatography (silicic acid TLC) to obtain crude cholesteryl glucopyranoside, which is further subjected to silicic acid TLC to obtain purified cholesteryl Glucopyranoside is obtained.

<Method for synthesizing steryl glucopyranoside>
In a suitable solvent, various sterols and acetohalogeno-α-D-glucopyranose are reacted at about room temperature in the presence of a catalyst such as mercury cyanide or silver oxide to give tetraacetylsteryl-β-D- After obtaining glucopyranoside, it is purified by silica gel column chromatography.
Next, this purified tetraacetylsteryl-β-D-glucopyranoside is hydrolyzed in, for example, methanol-water solvent at about room temperature to obtain the intended steryl-β-D-glucopyranoside.
In the case of synthesizing steryl-α-D-glucopyranoside, acetohalogeno-β-D-glucopyranose may be used in place of the raw material acetohalogeno-α-D-glucopyranose in the above method.

[plasmalogen]
The plasmalogen used in the present invention is a kind of phospholipids having an antioxidant effect and is one of glycerophospholipids. A unique subclass of glycerophospholipids characterized by having a vinyl ether bond at the sn-1 position of the glycerol backbone and found in high concentrations in the cell membranes of many mammalian tissues. Plasmalogens having a fatty acid ester bond at the sn-2 position are preferred.

The plasmalogen used in the present invention is not particularly limited as long as it is generally classified as a plasmalogen. Examples include choline-type plasmalogen, ethanolamine-type plasmalogen, inositol-type plasmalogen, and serine-type plasmalogen. can be mentioned. Among these, choline-type plasmalogen and ethanolamine-type plasmalogen are preferred, and ethanolamine-type plasmalogen is particularly preferred.

The plasmalogen of the present invention can be extracted from animal tissue. The animal tissue is not particularly limited as long as it contains plasmalogen, and includes aquatic animals such as shellfish, sea squirts, sea cucumbers, salmon, saury, and bonito, and birds. Among these, shellfish, sea squirts, and birds are preferred, and shellfish are particularly preferred. As the site to be used, an edible site (edible site) is preferable. These animal tissues may be cut pieces, but it is preferable to use pulverized pieces because plasmalogen can be extracted more efficiently.

Examples of shellfish include edible bivalves and snails such as scallops, mussels and abalones, with scallops being particularly preferred. Scallops are edible bivalves belonging to the mussel family, and include, for example, those belonging to the genus Mizuhopecten and the genus Pecten. Specifically, scallops collected in Japan (scientific name: Mizuhopecten yessoensis), European scallops collected in Europe (scientific name: Pectenmaximus (Linnaeus)), and the like can be mentioned. Examples of edible parts include scallops and cords.

The sea squirt is an edible chordate belonging to the Ascidaceae family, and includes those belonging to the genus Ascidia and the genus Ascidia. Concretely, it can be exemplified by Japanese wormwood (scientific name: Halocynthia roretzi), red wormwood (scientific name: Halocynthia aurantium), and the like. The edible part can include the body part (fascial body).

Birds are not particularly limited as long as they are edible birds, and examples thereof include chickens, silky fowls, and ducks. Breast meat rich in plasmalogen is preferable as the edible part.

Extraction of plasmalogen can be performed using water, an organic solvent, or a water-containing organic solvent, and it is preferable to use enzymatic treatment in combination. For example, an ethanol extraction method and a hexane extraction method can be mentioned, and the ethanol extraction method is preferable.

The ethanol extraction method is not particularly limited as long as it is a method of extraction using ethanol (including hydrous ethanol). The methods described in JP-A-2012-039472, JP-A-2010-065167, JP-A-2010-063406 and the like can be mentioned.

The hexane extraction method is not particularly limited as long as it is a method of extraction using hexane. .

The composition of the present invention can be used as an oral or parenteral formulation.
For parenteral use, external preparations and injections can be mentioned. The external preparation is not particularly limited as long as it is applied to the skin or scalp, and its forms include ointments, creams, gels, lotions, emulsions, packs, Skin external preparations such as poultices can be mentioned. When used as a hair growth and/or hair restorer, specific examples include hair tonics, shampoos, rinses, pomades, hair lotions, hair creams, hair treatments, and the like.

When used as an oral preparation, the forms thereof include, for example, tablets, capsules, powders, granules, liquids, granules, rods, plates, blocks, solids, rounds, pastes, and creams. , caplet-like, gel-like, chewable, stick-like, and the like. Among these, a capsule-like form is preferable.

The angiogenesis-promoting composition of the present invention contains sterylglucopyranoside and plasmalogen, and is not particularly limited as long as it can be distinguished from other products as a product in that it is used for angiogenesis. However, for example, so-called health products such as pharmaceuticals (including quasi-drugs), cosmetics, foods for specified health uses, foods with nutrient function claims, functional foods whose efficacy has been approved by a designated organization, etc. Foods and the like can be mentioned. In addition, the scope of the present invention also includes the products according to the present invention, which indicate on any of the body, packaging, instructions, and promotional materials that they have hair growth and/or hair restoration effects and wound healing effects.

The composition for hair growth and/or hair restoration of the present invention contains steryl glucopyranoside and plasmalogen, and can be distinguished from other products as a product in that it is used for hair growth and/or hair restoration. For example, pharmaceuticals (including quasi-drugs), cosmetics, food for specified health use, food with nutrient function claims, food with function claims, etc. So-called health foods such as functional foods can be mentioned. For example, in cosmetics and health foods, specifically, "grow hair", "promote hair growth", "promote hair growth", "prevent thinning hair", "those who are concerned about thinning hair", It is possible to display "For those who are concerned about hair loss" or the like.

The content (total amount) of steryl glucopyranoside and plasmalogen in the composition of the present invention may be appropriately contained within a range in which the effects thereof are exhibited. Depending on its form, for example, steryl glucopyranoside and plasmalogen are preferably 10 ^-10 % by mass or more, and 10 ^-5 % by mass or more, of the entire composition of the present invention in terms of dry mass. is more preferable, more preferably 0.1% by mass or more, and particularly preferably 1.0% by mass or more.

The compounding ratio (mass ratio) of steryl glucopyranoside and plasmalogen is preferably 1:0.001 to 1000, more preferably 1:0.01 to 100, more preferably 1:0.1. ∼10 is more preferable, and 1:0.2∼5 is particularly preferable.

The composition of the present invention may optionally be produced by a known formulation method by adding ingredients other than active ingredients (sterylglucopyranoside and plasmalogen) that are acceptable as oral agents, external agents, or injections. can be done.

Examples of ingredients other than the active ingredients of the present invention include vitamins, minerals, proteins, peptides, amino acids, animal oils, and vegetable oils. In addition, hydrocarbons, waxes, oils and fats, esters, higher fatty acids, higher alcohols, surfactants, fragrances, pigments, preservatives, antioxidants, and UV protection agents applied to hair growth and/or hair growth agents , alcohols, pH adjusters, etc., may be blended according to various purposes.

Hereinafter, the present invention will be described in detail based on examples.

A test using HDF-a cells (human fibroblasts) confirmed the effect of sterylglucopyranoside and plasmalogen, which are active ingredients of the composition of the present invention, on promoting the expression of vascular endothelial growth factor (VEGF).

[Cholesteryl glucopyranoside (CG)]
Cholesteryl glucopyranoside (manufactured by Sigma) dissolved in DMSO was used.

[Ethanolamine plasmalogen (PlsEtn)]
Ethanolamine-type plasmalogen was obtained by extracting scallop (scientific name: Mizuhopecten yessoensis) with ethanol and purifying it by HPLC.

[Cell culture]
Human Dermal Fibroblasts-adult (HDF-a) cells (#2320) were used as human fibroblasts. HDF-a cells were cultured in Fibroblast Medium (FM, #2301). Cells up to 6 passages were used for experiments.

HDF-a cells cultured from the previous day were cultured for 7 hours in the presence of 5 μg/ml CG and 5 μg/ml PlsEtn or in the presence of 5 ng/ml CG and 5 μg/ml PlsEtn.
For comparison, HDF-a cells were similarly cultured in the presence of CG alone, in the presence of PlsEtn alone, and in the absence of CG and PlsEtn.

[Analysis of promotion of VEGF expression]
The cultured HDF-a cells were collected with buffer A (0.25 M sucrose, 10 mM Hepes-KOH, pH 7.5, 1 mM EDTA) and centrifuged. The obtained cells were suspended in buffer A, disrupted by sonication, and after protein quantification, the same amount of protein was subjected to electrophoresis. They were then transferred to a PVDF membrane and detected by Western blotting using an anti-vascular endothelial growth factor (VEGF) antibody (Protein tech #19003-1-AP) and an anti-actin antibody (MBL #M177-3). The obtained signal of each protein was quantified with Multi Gauge software version 3.0 software (Fuji Film) and standardized by dividing the VEGF signal by the actin signal. Furthermore, the relative value of the VEGF signal intensity obtained during each treatment was shown as the difference between the average value and the average value of two trials, with the untreated value being 1.

FIG. 1 shows the results of VEGF expression in cultured HDF-a cells.

As shown in FIG. 1, HDF-a cells cultured in the presence of CG and PlsEtn exhibited enhanced VEGF expression compared to cells cultured in a medium containing only CG. Although VEGF expression was observed with PlsEtn alone, VEGF expression was synergistically enhanced when CG and PlsEtn were included. Therefore, CG and PlsEtn are expected to effectively promote VEGF biosynthesis.

In addition, keratinocytes, which are skin surface cells that express VEGF, do not exist in granulomas formed during skin wound healing, and VEGF is secreted from fibroblasts, which are the most diverse cell group that forms granulomas. It is known that
Increased VEGF expression in HDF-a cells promoted by CG and PlsEtn is thought to effectively restore and maintain skin homeostasis through induction of blood vessels such as wound healing and hair growth.

[Formulation Example 1]
A hair restorer (100 g) was produced according to the formulation shown below.
Cholesteryl glucopyranoside 0.5mg
Scallop extract plasmalogen 0.5mg
0.5 mg of glycerin
Remainder of purified water

[Formulation Example 2]
Hard capsules were produced according to the formulation shown below.
Cholesteryl glucopyranoside 0.5mg
Scallop extract plasmalogen 0.5mg
Cyclodextrin 3.3 mg
Amino acid 1.2mg
Paindex 185.0mg

The composition of the present invention can be used as an external preparation or an oral preparation, and is industrially useful.

Claims (3)

A composition for hair growth and/or hair restoration characterized by containing steryl glucopyranoside and plasmalogen ,
The steryl glucopyranoside is a compound represented by the following general formula (I),

(In the formula, Z represents cholesterol.)
The composition, wherein the plasmalogen is an ethanolamine-type plasmalogen. 2. The composition according to claim 1 , wherein said plasmalogen is derived from animal tissue. 3. The composition according to claim 2 , wherein said animal tissue is animal tissue selected from shellfish, sea squirts and birds.

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