Fibroblast growth promoter

Abstract

To provide a fibroblast growth promoter for promoting the growth of skin fibroblasts that exhibits enhanced preventive effects on skin aging such as wrinkles and sagging.SOLUTION: A fibroblast growth promoter contains argan oil. Preferably, the fibroblast growth promoter further contains cannabidiol. Also preferably, the fibroblast growth promoter is a topical skin preparation.SELECTED DRAWING: Figure 1

Description

[Technical field]

[0001] The present invention relates to a fibroblast proliferation promoter, and in particular to a fibroblast proliferation promoter that promotes the proliferation of skin fibroblasts and has improved preventive effects against skin aging such as wrinkles and sagging. [Background technology]

[0002] The structure of the skin is divided into the epidermis, which is responsible for the skin barrier function, and the dermis, which contains connective tissue and fat. Wrinkles and sagging of the skin are caused in part by the decrease in collagen fibers and elastic fibers present in the dermis. Therefore, the regeneration of collagen fibers and elastic fibers is effective in anti-aging, but it has been difficult to artificially regenerate collagen fibers and elastic fibers. In addition, dermal fibroblasts present in the dermis of the skin are cells that produce the constituent molecules of collagen fibers and elastic fibers. Like epidermal cells, dermal fibroblasts present in the dermis decrease with aging, and collagen fibers and elastic fibers in the dermis are decomposed more than synthesized, and therefore decrease. Therefore, increasing the number of dermal fibroblasts in the dermis leads to the inhibition of the decrease of collagen fibers and the regeneration of collagen fibers, and an anti-aging effect can be expected.

[0003] For example, Patent Document 1 discloses a fibroblast proliferation agent containing as an active ingredient a water-soluble component obtained from a hydrolysis product of ripe okra seeds with a protease, and Patent Document 2 discloses a fibroblast proliferation promoter characterized by containing as an active ingredient an acidic mucopolysaccharide or a physiologically acceptable salt or derivative thereof. [Prior art documents] [Patent documents]

[0004] [Patent Document 1] JP 2018-115143 A [Patent Document 2] JP 2014-1148 A Summary of the Invention [Problem to be solved by the invention]

[0005] However, the techniques described in Patent Documents 1 and 2 have been effective in vitro because the skin surface is covered with high molecular weight proteins, and so there is still room for improvement when it comes to actual skin.

[0006] Therefore, the object of the present invention is to solve the problems of the prior art and to provide a fibroblast proliferation promoter that promotes the proliferation of skin fibroblasts and has improved preventive effects against skin aging such as wrinkles and sagging, by focusing on the specific effects of argan oil. [Means for solving the problem]

[0007] As a result of intensive research aimed at solving the above problems, the inventors discovered that the above object could be achieved by the specific functions of argan oil itself, and thus completed the present invention.

[0008] That is, the fibroblast proliferation promoter of the present invention is characterized by containing argan oil.

[0009] In addition, it is preferable that the fibroblast proliferation promoter of the present invention further contains cannabidiol. Effect of the Invention

[0010] According to the present invention, a fibroblast proliferation promoter that promotes the proliferation of skin fibroblasts and has improved preventive effects against skin aging such as wrinkles and sagging can be provided. [Brief description of the drawings]

[0011] [Figure 1] 1 is a graph showing the results of a fibroblast proliferation test. [Diagram 2] 1 is a graph showing the decrease in fibroblasts with age. [Diagram 3]1 is a graph showing changes in collagen and elastin production with age. [Figure 4] FIG. 1 shows a diagram of subdivision. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0012] The fibroblast proliferation promoter of the present invention will be specifically described below. The fibroblast proliferation promoter of the present invention is characterized by containing argan oil. This can provide a fibroblast proliferation promoter that promotes the proliferation of skin fibroblasts and has improved preventive effects against skin aging such as wrinkles and sagging. Here, argan oil is a natural oil extracted from the fruit of the argan tree that grows in Morocco, and contains high concentrations of oleic acid and vitamin E. There is no limitation on such argan oil as long as it can provide the effects of the present invention and can be used in ordinary skin external preparations, and for example, argan oil manufactured by Hoshi Chemicals Co., Ltd. can be used. The amount of such argan oil to be added is preferably 0.01 to 20% by mass, more preferably 1 to 5% by mass.

[0013] Figure 2 is a graph showing the decrease in fibroblasts with age, Figure 3 is a graph showing the change in collagen and elastin production with age, and Figure 4 is a diagram showing the division. In the dermis layer of the skin, collagen and elastin fibers are formed in a mesh-like structure, with hyaluronic acid filled with water between them. These three components play an important role in beautiful skin, and the cells that produce these beautiful skin components are fibroblasts. In order to maintain beautiful skin, it is important that these fibroblasts are always functioning actively. However, as we age, the number of active and high-quality fibroblasts decreases, and the ability to produce new fibroblasts also decreases. Fibroblasts in the dermis tend to decrease after the age of 30, and the number and production ability of high-quality fibroblasts decreases proportionally, and collagen and elastin in the dermis decrease rapidly after the age of 40. As a result, the collagen, elastin, and hyaluronic acid produced in the dermis also decrease, causing the skin to lose elasticity, which appears as wrinkles and sagging. In addition, fibroblasts are produced by repeated cell division and differentiation from stem cells in the dermis. These fibroblasts then produce protein fibers such as collagen and elastin, and skin-beautifying components such as hyaluronic acid. Therefore, when fibroblasts are active, it is possible to maintain elastic and healthy skin. In addition, large blood vessels such as arteries and veins are composed of fibroblasts, collagen, elastin, etc. Fibroblasts are always close to blood vessels, and as the function of blood vessels declines, fibroblasts release a cell growth factor called VEGF (Vascular endothlial growth factor), which also plays a role in supporting the creation of new blood vessels. Therefore, the creation of flexible blood vessels by fibroblasts is also directly linked to maintaining a person's health and youthful skin. Furthermore, when the skin is damaged by an injury, fibroblasts migrate to the damaged area and produce a large amount of collagen (protein), helping to repair the skin. At this time, it is thought that the proliferation ability of fibroblasts is fully exerted, and the area damaged by the wound is regenerated into strong skin by the three forces of fibroblasts + capillaries + collagen. In this way, fibroblasts not only increase collagen, but also monitor all aspects of aging and act immediately when needed.

[0014] In addition, the fibroblast proliferation promoter of the present invention preferably further contains cannabidiol. Substances that increase the expression of aquaporin (AQP) 3 improve dry skin associated with aging and are effective for beauty, and cannabidiol has the effect of increasing the expression of aquaporin (AQP) 3. Therefore, by using argan oil and cannabidiol in combination, the expression of aquaporin (AQP) 3 can be increased, thereby suppressing dry skin associated with aging and further improving the moisturizing effect. Here, cannabidiol is a type of cannabinoid, which is a polyphenol contained in hemp, and is represented as "CBD". In the present invention, there is no limitation as long as it can be used in a normal skin external preparation, but for example, "CBD crystalline powder" from PharmaHemp Laboratories (Ljubljana, Slovenia) can be used. The amount of cannabidiol to be added is preferably 0.1 to 10% by mass, more preferably 1 to 5% by mass.

[0015] Furthermore, the fibroblast proliferation promoter of the present invention is preferably used as an external preparation for the skin, which promotes proliferation of fibroblasts in the skin, suppresses dry skin associated with aging, and further improves the moisturizing effect.

[0016] In the present invention, the topical skin preparation is not particularly limited as long as it can be used on human skin, etc., and is primarily a cosmetic (cosmetic material), but does not exclude applications as quasi-drugs, pharmaceuticals, etc. Furthermore, the cosmetic (cosmetic material) includes basic cosmetics, makeup cosmetics, hair cosmetics, bath additives, etc.

[0017] Furthermore, in the present invention, other ingredients can be appropriately added within a range that does not impair the effects of the present invention. Any ingredient other than those mentioned above can be blended within a qualitative and quantitative range, and ingredients that are usually blended in external preparations, particularly cosmetics, such as surfactants, oily ingredients, moisturizing agents, antioxidants, fragrances, various vitamin preparations, chelating agents, colorants, ultraviolet absorbing agents, medicinal ingredients, inorganic salts, etc. can be blended.

[0018] Examples of ingredients that can be added include nonionic surfactants, such as mono-fatty acid polyglyceryl, poly-fatty acid polyglyceryl, polyoxyethylene glycerin fatty acid esters, polyoxyethylene sorbitan fatty acid esters, polyoxyethylene sorbit fatty acid esters, polyoxyethylene propylene glycol fatty acid esters, polyoxyethylene castor oil derivatives, polyoxyethylene hydrogenated castor oil derivatives, polyoxyethylene sterols, polyoxyethylene hydrogenated sterols, polyethylene glycol fatty acid esters, polyoxyethylene alkyl ethers, polyoxyethylene polyoxypropylene alkyl ethers, and sucrose fatty acid esters.

[0019] Examples of amphoteric surfactants include imidazoline-based amphoteric surfactants such as 2-undecyl-N,N,N-(hydroxyethylcarboxymethyl)-2-imidazoline sodium and 2-cocoyl-2-imidazolinium hydroxide-1-carboxyethyloxy 2-sodium salt, and betaine-based surfactants such as 2-heptadecyl-N-carboxymethyl-N-hydroxyethylimidazolinium betaine, lauryl dimethylaminoacetate betaine, alkyl betaines, amido betaines, and sulfobetaines.

[0020] Examples of polyhydric alcohols include one or more selected from the group consisting of glycerin, 1,3-butylene glycol, propylene glycol, propanediol, 1,2-hexanediol, pentylene glycol, pentaerythritol, hexylene glycol, diglycerin, polyglycerin, diethylene glycol, polyethylene glycol, dipropylene glycol, polypropylene glycol, ethylene glycol-propylene glycol copolymers, and polymers thereof.

[0021] Examples of polymer components include xanthan gum, gellan gum, gum arabic, tragacanth gum, galactan, guar gum, carrageenan, pectin, agar, quince seed, dextran, pullulan, casein, carboxymethylcellulose, hydroxyethylcellulose, hydroxypropylmethylcellulose, gelatin methylcellulose, sodium alginate, and carboxyvinyl polymer.

[0022] Examples of extract components include chamomile extract, parsley extract, honeysuckle extract, rice extract, rice bran extract, hop extract, phellodendron bark extract, coix seed extract, Swertia japonica extract, melilot extract, birch extract, licorice extract, peony extract, soapwort extract, loofah extract, chili pepper extract, lemon extract, gentiana extract, perilla extract, aloe extract, rosemary extract, sage extract, thyme extract, eucalyptus extract, tea extract, seaweed extract, cucumber extract, clove extract, carrot extract, horse chestnut extract, witch hazel extract, mulberry extract, chinpi extract, pecan nut extract, grapefruit extract, shekwasha extract, passion fruit extract, loquat extract, grape extract, rose fruit extract, sophora flavescens extract, and peppermint extract.

[0023] Other moisturizing ingredients include, for example, xylitol, sorbitol, maltitol, sodium chondroitin sulfate, elastin, glucosamine, hyaluronic acid, cyclodextrin, collagen, bile salts, and the like.

[0024] Examples of medicinal ingredients include vitamins such as vitamin A, vitamin B, vitamin C, vitamin D, and vitamin E and their derivatives, glycyrrhizinic acid and its derivatives, various salts of urea, creatinine, CoQ10, astaxanthin, polyphenols, and ceramides.

[0025] Examples of ultraviolet absorbers include benzophenone derivatives such as 2-hydroxy-4-methoxybenzophenone, para-aminobenzoic acid derivatives such as para-aminobenzoic acid, methoxycinnamic acid derivatives such as octyl paramethoxycinnamate, salicylic acid derivatives such as octyl salicylate and phenyl salicylate, urocanic acid, ethyl urocanate, 4-tert-butyl-4' methoxydibenzoylmethane, and benzotriazole.

[0026] In addition, in the present invention, the topical skin preparation can be produced by a method for producing the same using a conventional cosmetic production method, such as a method of heating an oil phase component and an aqueous phase component or a D-phase emulsification method.

[0027] Furthermore, the method of using the topical agent of the present invention is not particularly limited as long as it can be applied to the skin, etc., and the topical agent may be applied directly to the skin by hand or directly from a container, etc.

[0028] The present invention will be described in more detail below using examples, but the present invention is not limited to these examples. In the following "Examples", the blending percentage indicates mass %. In the figure, "AO" indicates argan oil, "OL" indicates olive oil, "EOH" indicates ethanol, "NT" indicates untreated, "%" indicates blending mass %, and "Ctrl" indicates control. EXAMPLES

[0029] (Fibroblast proliferation test) The effect of argan oil on human fetal skin fibroblasts was tested. Argan oil (AO) manufactured by Hoshi Chemicals Co., Ltd. and olive oil (OL) manufactured by Wako Pure Chemical Industries, Ltd. were used, and each was diluted with ethanol to 50% by mass to prepare a sample solution. As a control, water diluted with ethanol to 50% by mass was used. Human fetal skin fibroblasts (NHDF) were cultured in 10% FBS MEMα under conditions of 37°C and 5% CO2.

[0030] (measurement) The cell count was measured as the absorbance (Ab) at 450 nm using Cell Counting Kit-8 (Dojindo Laboratories, Inc.). Argan oil (AO) and olive oil (OL) were diluted in serum-free medium (SF) at 0.13 mass%, 0.25 mass%, and 0.5 mass%, and the cells were added and cultured for 4 hours (4h) and 48 hours (48h). In serum-containing medium, both argan oil (AO) and olive oil (OL) became cloudy even at a concentration of 0.5 mass%, so all experiments were performed in serum-free medium.

[0031] FIG. 1 is a graph showing the results of the fibroblast proliferation test. As shown in FIG. 1, argan oil (AO) increased the cell number in a concentration-dependent manner from 0.13% by mass, but olive oil (OL) did not increase the cell number. Furthermore, no cytotoxicity was observed in either argan oil (AO) or olive oil (OL) in the concentration range used in this study (0.13% by mass to 0.5% by mass). This shows that argan oil (AO), unlike olive oil (OL), promoted the proliferation of skin fibroblasts.

[0032] (Examples 1 to 2) A fibroblast proliferation promoter containing argan oil (AO) of Examples 1 and 2 was prepared in the amounts shown in Table 1 below. The production method was as follows: (1) heating ingredients No. 1, 3, 4, and 13 to 15 in Table 1 to 80°C, (2) heating ingredients No. 2, 5 to 10, 12, and 16 in Table 1 to 80°C, (3) mixing and stirring (1) and (2) at 80°C, (4) cooling (3) to 50°C with stirring, adding ingredient No. 11 in Table 1, and cooling to room temperature.

[0033] (Table 1) TIFF2025009078000002.tif145144

[0034] The fibroblast proliferation promoters of Examples 1 and 2 all showed improved preventive effects against skin aging such as wrinkles and sagging.

Claims

1. A fibroblast proliferation promoter characterized by containing argan oil.

2. The fibroblast proliferation promoter according to claim 1, further comprising cannabidiol.

Images