Angiogenic factor production promoters, topical skin preparations, and scalp cosmetics

Abstract

To discover an ingredient having an angiogenic factor production promoting action from specific plants, create a novel angiogenic factor production promoter comprising such a component as an active ingredient, and blend the active ingredient in a topical skin preparation or a scalp cosmetic to be utilized for sound hair growth.SOLUTION: An angiogenic factor production promoter comprises Senecio herreanus f.variegata extract as an active ingredient, which is used to prepare a topical skin preparation such as a scalp cosmetic capable of promoting the production of a vascular endothelial growth factor (VEGF) and a basic fibroblast growth factor (bFGF).SELECTED DRAWING: None

Description

Technical Field

[0001] The present invention relates to an angiogenesis factor production promoter containing a plant-derived component and a topical skin preparation such as a scalp cosmetic using the angiogenesis factor production promoter.

Background Art

[0002] Generally, hair is a general term for human hair including scalp hair, and it repeatedly grows and falls out periodically throughout life. In particular, scalp hair growing on the head and eyebrows around the eyes greatly affect a person's appearance and impression. It is not easy to always keep such hair in good condition. The healthy state is impaired by various factors such as internal factors such as aging and temporary social stress, or external factors such as ultraviolet rays. Therefore, many people, regardless of gender, have troubles regarding hair.

[0003] For example, the causes of the appearance of symptoms such as thinning hair and hair loss include genetics, stress, or clogging of hair follicles due to sebum trouble. However, poor blood flow state of the skin also causes the above symptoms. When the blood flow state of the skin deteriorates, the blood flow volume to hair papilla cells and hair follicles decreases, and the nutrient supply to these cells becomes insufficient, so the hair growth rate decreases.

[0004] As a substance necessary for improving blood flow in the skin so that hair is kept healthy, vascular endothelial growth factor (VEGF) necessary for angiogenesis is known. This is a glycoprotein secreted by epidermal keratinocytes, fibroblasts, etc., and is involved in the process of angiogenesis and formation, and contributes to the enhancement of blood circulation and vascular permeability.

[0005] For example, in hair papilla cells present in hair follicles, when the gene producing VEGF is expressed, the secreted VEGF is known to act on cells autocrine and participate in hair elongation (see Patent Document 1 and Patent Document 2).

[0006] Furthermore, it is known that increased expression of VEGF leads to the formation of new blood vessels, which in turn promotes blood circulation and improves blood flow (see Patent Document 3).

[0007] Besides VEGF, another glycoprotein that acts as an angiogenic factor is basic fibroblast growth factor (bFGF), which is secreted in epidermal keratinocytes and fibroblasts in the skin. bFGF's release from epidermal keratinocytes is promoted by ultraviolet irradiation, and it acts on melanocytes in the epidermis, promoting cell division of melanocytes and accelerating melanin synthesis (see Patent Document 4).

[0008] Furthermore, it is known that injecting bFGF solution intradermally or subcutaneously can promote hair growth and prevent hair loss (see Patent Documents 5 and 6).

[0009] As mentioned above, promoting VEGF production enhances angiogenesis, leading to hair growth effects, while a decrease in VEGF expression results in a decrease in hair elasticity and resilience. Therefore, in order to prevent hair problems such as hair loss, it is necessary to improve the scalp environment, and oral or parenteral administration of VEGF production-promoting components is an effective means (see Patent Document 7).

[0010] Here, regarding the origin of the VEGF production-promoting component and the bFGF production-promoting component mentioned above, the VEGF in Patent Document 1 is contained in amber, and it is also contained in the aloe extract obtained from the aloe plant of the Asphodelaceae family described in Patent Document 2.

[0011] Furthermore, Patent Document 3 describes VEGF derived from "bee larvae (bee larvae and pupae)," and Patent Document 4 describes that water or lower alcohol extracts from "purple rice bran" suppress the increase in bFGF mRNA expression.

[0012] Furthermore, Patent Document 5 describes VEGF derived from deep-sea water, and Patent Document 6 describes bFGF extracted from blood.

[0013] It is known that components useful for hair health, such as VEGF production-promoting components or bFGF production-promoting components, can be extracted from specific cultivateable plants. For example, Patent Document 7 describes a VEGF production promoter that uses a type of saponin derived from a plant of the genus Ruscus in the family Liliaceae as an active ingredient. Furthermore, Patent Document 8 describes that extracts of Senecio gracilis, a member of the Senecio genus in the Asteraceae family, obtained using ethanol or organic solvents as extraction solvents, inhibit dopa oxidase and have a skin-whitening effect. [Prior art documents] [Patent Documents]

[0014] [Patent Document 1] Japanese Patent Publication No. 2011-256164 [Patent Document 2] Japanese Patent Publication No. 2015-034157 [Patent Document 3] Japanese Patent Publication No. 2020-002034 [Patent Document 4] Japanese Patent Publication No. 2011-126850 [Patent Document 5] Japanese Patent Publication No. 2018-058793 [Patent Document 6] Special Publication No. 2018-512371 [Patent Document 7] Japanese Patent Publication No. 2012-012357 [Patent Document 8] Japanese Patent Publication No. 2010-195732 [Overview of the Initiative] [Problems that the invention aims to solve]

[0015] However, the fact that inhibiting dopa oxidase described in Patent Document 8 has a whitening effect has nothing to do with hair growth. Further, the melanogenesis-inhibiting component extracted from Senecio gracilis described in the same patent document is not known for its promoting effect on the production of angiogenic factors, and Patent Document 8 also does not describe such properties.

[0016] Incidentally, since melanin-producing components may be more easily released when blood vessels abnormally proliferate, components having an angiogenic factor production-promoting effect are unnecessary components in whitening agents that inhibit the production of melanin, which is the cause of freckles.

[0017] Therefore, even in Patent Document 8 that uses an extract from a plant belonging to the same genus as Senecio herreanus f. variegata, it is considered that verification of the angiogenic factor production-promoting effect of substances that are contrary to the purpose of inhibiting melanin production was unnecessary.

[0018] Therefore, the problem of this invention is to find a component having an angiogenic factor production-promoting effect from a specific plant that has not been used so far, create an angiogenic factor production-promoting agent containing such a component as an active ingredient, and further use them as external skin preparations and scalp cosmetics containing the above-mentioned active ingredient so that they can be used for healthy hair growth.

Means for Solving the Problem

[0019] The inventors of the present application investigated the possibility that an unknown useful component is contained in an extract of Senecio herreanus f. variegata, which is cultivated as an ornamental succulent plant, and confirmed by experiments that the extract has a promoting effect on the production of angiogenic factors such as vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF). Based on this discovery, the invention was completed. That is, in order to solve the above problems, in this invention, an angiogenesis factor production promoter containing an extract of Senecio herreanus f. variegata as an active ingredient was used.

[0020] The angiogenesis factor production promoter of this invention uses a plant body such as the leaves or stems of Senecio herreanus f. variegata as an extraction material, and uses an extract such as a lower alcohol such as ethyl alcohol as an active ingredient, and can promote the production of angiogenesis factors in the skin such as the scalp. As a result, the skin and the existing hair can be kept healthy so as to be useful for hair growth.

[0021] It has been confirmed from the test results described later that the angiogenesis factor in the angiogenesis factor production promoter is Vascular Endothelial Growth Factor (VEGF) or basic Fibroblast Growth Factor (bFGF).

[0022] VEGF or bFGF is considered to be a substance that acts on predetermined cells in the skin, is involved in the process of blood vessel neovascularization and formation, promotes blood circulation, keeps the hair papilla cells present in the hair follicle healthy, and enables healthy hair growth.

[0023] A topical skin preparation containing such an angiogenesis factor production promoter is formulated as an active ingredient so that hair can grow on the hair of other required parts of a human, and the topical skin preparation can be applied to a topical skin preparation that helps grow the hair or body hair at required sites such as hair, eyebrows, and eyelashes, particularly a scalp cosmetic.

Effect of the Invention

[0024] This invention has the advantage of discovering new properties of an extract from angel's tears, a specific cultivable plant, specifically its ability to promote the production of VEGF and bFGF, which are angiogenic factors. This allows for the proposal of a new use for the extract as an angiogenic factor production promoter, and enables the creation of topical skin preparations and scalp cosmetics containing this active ingredient, which can then be used for healthy hair growth. [Brief explanation of the drawing]

[0025] [Figure 1] Figure and table showing the VEGF gene expression level in extract preparation example 1 compared to the control. [Figure 2] Figure and table showing the bFGF gene expression level in extract preparation example 1 compared to the control. [Modes for carrying out the invention]

[0026] As embodiments of the angiogenic factor production promoter of this invention, an extract of the plant body of Angel Tears (Senecio herreanus f. variegata) is described in detail below as a vascular endothelial growth factor (VEGF) production promoter or a basic fibroblast growth factor (bFGF) production promoter, with this extract as the active ingredient.

[0027] The angel tears used as the extraction material in this embodiment is Senecio herreanus f. variegata, a species of angel tears belonging to the genus Senecio in the family Asteraceae.

[0028] The parts of the plant that can be used as raw materials for extraction are not limited to any particular part, and may include, for example, the above-ground parts such as leaves, stems, branches, pulp, and pericarp, or the entire plant (whole plant) including rhizomes, root bark, or roots. For example, the above-ground parts, including thickened leaves and stems that are easy to collect, are preferable parts for efficiently producing extracts because they are easy to collect and the plant regenerates quickly.

[0029] The extracts from the above-mentioned plants can be extracted using non-polar solvents such as organic solvents or polar solvents such as alcohols or aqueous solvents, without limiting the extraction solvent. For example, extracts obtained using lower alcohols as the extraction solvent can be obtained by conventional extraction processes, such as adjusting the concentration of the extraction solvent during extraction.

[0030] The lower alcohols used as extraction solvents in the above examples are aliphatic alcohols with 5 or fewer carbon atoms and a valency of monohydric to trihydric. Specific examples of lower alcohols include methyl alcohol, ethyl alcohol, ethylene glycol, propyl alcohol, glycerin, isopropyl alcohol, butyl alcohol, and pentyl alcohol.

[0031] It is preferable to selectively use such extraction solvents that can be safely used as solvents in cosmetics, etc., so that the solvent removal process in the manufacturing process can be simplified.

[0032] For example, the lower alcohol-soluble component obtained as an extract is obtained by separating an extract that exhibits solubility in lower alcohols such as ethanol at least in the final extraction stage, and in the initial or intermediate steps of the extraction, an extraction solvent other than a lower alcohol may be used as needed.

[0033] In this case, examples of extraction solvents other than lower alcohols include aqueous solvents (polar solvents) such as water, ether, n-hexane, and toluene, higher alcohol-based solvents, and organic solvents (non-polar solvents). Furthermore, the extraction solvent and extraction method before the final treatment are not limited, and well-known extraction solvents or extraction methods with adjusted pressure and temperature can be used as appropriate.

[0034] Specific extraction methods that can be used in the embodiments include, for example, immersing the raw materials in an extraction solvent such as ethanol (99.5% concentration) in an amount (by mass ratio) of 5 to 10 times that of Angel Tears, eluting the components at room temperature or under reflux heating, and then filtering the extraction residue to separate the solid and liquid components.

[0035] The obtained extract may be used as is, or it may be diluted or concentrated and further dried to obtain a solid extract. Alternatively, the concentrate or dried product may be dissolved or suspended in a suitable solvent, and further purification or other treatments may be performed as appropriate to obtain a crude or purified product.

[0036] Thus, the angel tears extract may be an extract solution, a diluted or concentrated extract solution, a solid substance obtained by drying these extracts, or a crude or purified product.

[0037] Furthermore, the angel tears extract in this invention has the effect of promoting the production of VEGF and bFGF, and by utilizing these effects, it can be used as a VEGF production promoter, a bFGF production promoter, and a topical skin preparation such as a scalp cosmetic containing these as active ingredients.

[0038] When the VEGF production promoter and bFGF production promoter in this invention are used in scalp cosmetics, their content as active ingredients is 0.00001 to 0.01% by mass, and more preferably 0.0001 to 0.001% by mass, based on the dry weight of the above extract. When human epidermal keratinocytes are cultured at the above preferred content, the cell viability is approximately 100%, indicating that the above extract is extremely safe for the skin.

[0039] As for the formulation form of topical skin preparations such as scalp cosmetics, this invention can be prepared in various forms as long as the effects are not impaired, and it may be in any form such as solid, liquid, or gel, and the most optimal known form can be selectively adopted for the final product.

[0040] While there are no particular limitations on the method of administering topical skin preparations such as scalp cosmetics, it is preferable to administer an appropriate amount at the appropriate time to the skin, including the scalp, by brushing on creams or droplets, dropping or spraying droplets, applying them as a compress, or immersion.

[0041] The formulation form and composition of the topical skin preparations applicable to the scalp cosmetic of this invention are not particularly limited, and examples include cosmetics such as shampoos, conditioners, treatments, hair tonics, hair liquids, hair creams, hair gels, and hair sprays. In addition to scalp cosmetics, lotions, emulsions, creams, body soaps, hand creams, ointments, and bath additives can also contain angiogenic factor production promoters.

[0042] The above-mentioned topical skin preparation may be formulated in combination with the necessary main ingredients or other additives used in the manufacture of ordinary scalp cosmetics, as long as they do not interfere with the VEGF production-promoting effect and bFGF production-promoting effect of the angel tears extract.

[0043] Possible ingredients include oily components, emulsifiers, humectants, thickeners, medicinal ingredients, preservatives, pigments, powders, pH adjusters, UV absorbers, antioxidants, and fragrances, and these are added in appropriate amounts depending on the purpose of the formulation.

[0044] Specific examples of oily components include liquid paraffin, petrolatum, microcrystalline wax, squalane, jojoba oil, beeswax, carnauba wax, lanolin, olive oil, coconut oil, higher alcohols, fatty acids, esters of higher alcohols and fatty acids, and silicone oils.

[0045] Examples of emulsifiers include nonionic surfactants such as polyoxyethylene alkyl ethers, polyoxyethylene fatty acid esters, polyoxyethylene sorbitan fatty acid esters, sorbitan fatty acid esters, glycerin fatty acid esters, polyglycerin fatty acid esters, and polyoxyethylene hydrogenated castor oil; anionic surfactants such as sodium stearoyl lactylate; amphoteric surfactants such as soybean phospholipids; and cationic surfactants such as alkyltrimethylammonium chloride.

[0046] Examples of thickening agents include carboxyvinyl polymers, xanthan gum, methylcellulose, polyvinylpyrrolidone, gelatin, and clay minerals such as bentonite.

[0047] Furthermore, examples of the medicinal ingredients that can be incorporated include various vitamins and their derivatives, allantoin, glycyrrhizic acid and its derivatives, various animal and plant extracts, and other anti-aging agents, moisturizers, transdermal absorption enhancers, UV absorbers, cell activators, anti-inflammatory agents, whitening agents, and antiseptics / antifungal agents. [Examples]

[0048] [Example 1 of Angel Tears Extract Production] Angel Tears extract was prepared by finely chopping 443.41 g of the above-ground parts (leaves and stems) of Angel Tears (Senecio herreanus f. variegata), excluding the roots, and immersing them in approximately five times the volume (by mass) of ethanol (99.5% concentration) as an extraction solvent. Soluble components were extracted under reflux heating, and the extract residue was removed by filtration and then concentrated. The yield of the extraction using ethanol as the extraction solvent in this process was 0.67%.

[0049] Using the obtained ethanol-soluble component, an angiogenic factor production promoter (Example 1) containing 0.01 mg / ml (0.001% by mass) of this component on a concentrated dry basis was examined to investigate whether it promoted the production of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF). The expression levels of VEGF(A)-producing genes and bFGF-producing genes in human stratum corneum cells were investigated using the following test method, and the results are shown in Figures 1 and 2.

[0050] <Testing Method> Normal human epidermal keratinocytes (NHEK: Kurabo) were cultured in HuMedia-KB2® medium containing a low concentration of BPE (without bFGF or VEGF as additives) in a 6-well plate at a rate of 3.8 × 10⁶ per well. 5Cells were seeded individually and cultured overnight in an incubator set to 37°C and 25% CO2. After the culture period, 3 mL of the test sample dissolved in culture medium (containing 0.01 mg / ml of ethanol-soluble component as a concentrated dry product) was added to each cell and cultured. After 24 hours, the sample was removed and washed, and the total RNA was extracted using NucleoSpin® RNA Plus (Takara Bio). The obtained total RNA was reverse transcribed using PrimeScript® RT reagent Kit (Takara Bio) to synthesize cDNA.

[0051] The obtained cDNA was subjected to RT-PCR using SYBR® Premix Ex Taq™ II (Takara Bio Inc.), and the expression levels of mRNA for VEGF(A) production genes and bFGF production genes were measured.

[0052] Gene expression was evaluated using the comparative Ct method, and each expression level was corrected to a relative value with the expression level of the control GAPDH (glyceryl aldehyde-3-phosphate dehydrogenase) producing gene set to 1. The forward and reverse primers for each gene are shown in Table 1, and the test results are also shown in Table 2.

[0053] [Table 1]

[0054] [Table 2]

[0055] As is clear from the results shown in Table 2 and Figures 1 and 2, Example 1 of the angiogenic factor production promoter containing an ethanol-soluble component extracted from the plant body of Angel Tears (Senecio herreanus f. variegata) was confirmed to promote the expression of the gene (mRNA) that produces VEGF(A) or the gene (mRNA) that produces bFGF, respectively, in normal human epidermal keratinocytes. Similarly, the same effectiveness was observed even when the ethanol-soluble component was contained at a concentration of 0.005 mg / ml on a dry weight basis, indicating that effectiveness was observed even at extremely small amounts. This indicates that the above ethanol-soluble component can be included as an active ingredient in VEGF production promoters or bFGF production promoters, which are angiogenic factor production promoters.

[0056] The composition (mass %) of Example 2-4 (scalp cosmetic containing an angiogenic factor production promoter as an active ingredient) is shown below, in which the ethanol-soluble component obtained in Production Example 1 (referred to as "Angel Tears Extract (Extract Production Example 1)" in the composition) is incorporated at a concentration equivalent to 0.001% of the concentrated dry product.

[0057] [Example 2] (Scalp cosmetic: Shampoo) Angel Tears Extract (Extract Production Example 1) 0.001 Glycerin 5.0 Sodium laureth sulfate 5.0 Cocamidopropyl betaine 4.0 Cocamide MEA 1.0 Polyquaternium-10 0.3 pH adjuster (appropriate amount) Fragrance (appropriate amount) Preservative (appropriate amount) Purified water remainder

[0058] [Example 3] (Scalp cosmetic: Treatment) Angel Tears Extract (Extract Production Example 1) 0.001 Glycerin 5.0 Sterial alcohol 5.0 Silicone 5.0 Behentrimonium chloride 2.0 Cetyl ethylhexanoate 2.0 Fragrance (appropriate amount) Preservative (appropriate amount) Purified water remainder

[0059] [Example 4] (Scalp cosmetic: Scalp lotion) Angel Tears Extract (Extract Production Example 1) 0.001 Glycerin 5.0 1,3-Butylene glycol 10.0 Fragrance (appropriate amount) Preservative (appropriate amount) Purified water remainder [Industrial applicability]

[0060] This invention, as an angiogenic factor production promoter that promotes the production of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF), can be used in cosmetics such as topical skin preparations and scalp cosmetics. Therefore, it can be used in fields such as cosmetics, quasi-drugs, pharmaceuticals, and food products where these effects are desired by consumers. Furthermore, it can also be used as a positive target (reagent) for research purposes when performing material screening of extracted materials.

Claims

1. An angiogenesis factor production promoter containing an ethanol extract of the leaves or stems of Angel Tears (Senecio herreanus f. variegata) as an active ingredient that promotes the production of vascular endothelial growth factor (VEGF) or basic fibroblast growth factor (bFGF).

2. A topical skin preparation containing the angiogenic factor production promoter described in claim 1 as an active ingredient.

3. A scalp cosmetic comprising the topical skin preparation described in claim 2.

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