JP2008105983A - Fibroblast proliferation promoter, skin care preparation for external use, bathing agent, and food and drink - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a fibroblast proliferation promoter that increases the amount of collagen and hyaluronic acid present in the skin and prevents, ameliorates and improves wrinkles and flabby skin, and to provide a skin care preparation for external use, a bathing agent, and foods and drinks comprising the fibroblast proliferation promoter. <P>SOLUTION: The fibroblast proliferation promoter comprises one or two or more selected from among Polygala tenuifolia extracts, Sophora flavescens extracts, Peonia lactiflora extracts, Diospyros kaki extracts, Salvia miltiorrhiza extracts, Centella asiatica extracts, puer extracts, arbutin, ascorbic acid and oligosaccharide alginates. The skin care preparation for external use, the bathing agent, and foods and drinks comprise the fibroblast proliferation promoter. <P>COPYRIGHT: (C)2008,JPO&INPIT

Description

  The present invention relates to a fibroblast growth promoter that plays an important role in skin elasticity, tension and moisture. Furthermore, it is related with the skin external preparation, the bath preparation, and food and drink containing this fibroblast growth promoter.

  In recent years, the awareness of beauty has improved with the aging of society and the advancement of women into society. However, the function of the skin decreases with age, and with age, it loses its elasticity and tension, and wrinkles occur. This may be due to a decrease in the amount of collagen and hyaluronic acid produced by fibroblasts present in the skin.

  The skin consists of three layers of the subcutaneous tissue, the dermis, and the epidermis. The dermis has the most influence on the skin function such as the elasticity of the skin, and the dermis is rich in collagen and hyaluronic acid. These collagen and hyaluronic acid are known to be produced by fibroblasts present in the dermis, and play an important role in maintaining the elasticity of the skin.

  In addition to dermis, fibroblasts are scattered throughout the connective tissues throughout the body and are known to play an important role in the connection of tissues and organs. It is expected to be applied to the treatment of wounds, prevention of fibroma, and prevention of aging.

Various means have been proposed so far to maintain the elasticity of the skin, that is, to prevent skin aging. For example, Patent Document 1 describes “external preparation for skin containing genquanine as an active ingredient”. Genkwanin contained in the external preparation for skin described in Patent Document 1 promotes collagen and hyaluronic acid production in fibroblasts and does not promote proliferation of fibroblasts. In addition, Patent Document 1 discloses that specific plant extracts such as citrus extract or specific compounds such as ascorbic acid promote the growth of fibroblasts. As a result, the production of collagen and hyaluronic acid is improved. Nothing is disclosed about preventing aging.
JP 2004-137217 A

  The present invention improves the amount of collagen and hyaluronic acid present in the skin, and prevents collagen, hyaluronic acid, and fibroblasts that produce collagen and hyaluronic acid to regain skin elasticity and tension by preventing, mitigating, and improving And an external preparation for skin, bath preparation, and food and drink containing the fibroblast growth promoter.

  As a result of intensive studies to solve the above problems, the present inventors have found that specific plant extracts, arbutin, ascorbic acid, and alginic acid oligosaccharides have an action of promoting the proliferation of fibroblasts. The present invention has been completed based on the findings.

That is, the present invention is characterized by containing one or more selected from Itohime extract, Clara extract, peony extract, oyster extract, tanjin extract, camellia extract, puer extract, arbutin, ascorbic acid and alginate oligosaccharides. A fibroblast proliferation promoter is provided.
Moreover, this invention provides the skin external preparation, the bath preparation, or food-drinks characterized by including the said fibroblast proliferation promoter.

  Itohimeha extract, Clara extract, Peonies extract, Oyster extract, Tanjin extract, Clover extract, Puaru extract, Arbutin, Ascorbic acid and Alginate oligosaccharides are each alone, and in particular, have the action of promoting fibroblast proliferation, It is useful in various applications as a fibroblast growth promoter. By using or ingesting cosmetics, quasi-drugs, bath preparations and foods and drinks containing these, the effect of proliferating fibroblasts can be expected, thus preventing and improving the aging phenomenon of the skin and the like. .

  The fibroblast growth promoter according to the present invention comprises one or more selected from the group consisting of citrus extract, clara extract, peony extract, oyster extract, tandin extract, camellia extract, puer extract, arbutin, ascorbic acid and alginate oligosaccharide. It is characterized by containing.

As the fibroblast proliferation promoter of the present invention containing two or more selected from the plant extract, arbutin, ascorbic acid and alginate oligosaccharides,
A combination of an alginic acid oligosaccharide and arbutin, communis extract, tandin extract, citrus extract, oyster extract, clara extract or puer extract;
A combination of arbutin and ascorbic acid, Clara extract or Puaru extract;
A combination of Itohimehagi extract and Puaru extract, Tanjin extract or Clara extract;
A combination of Clara extract and Peonies extract, Clover extract or Puer extract;
Combination of peony extract and oyster extract;
A combination of alginate oligosaccharide, arbutin and oyster extract;
A combination of alginate oligosaccharides, Clara extract, and puer extract;
A combination of alginate oligosaccharides, Itohime extract, and Clara extract;
A combination of arbutin, clara extract and puer extract;
A combination of oyster extract, Clara extract, and Clover extract;
A combination of Itohimehae extract, oyster extract, tanjin extract, and camellia extract;
Those containing a combination selected from the above are preferable because they are particularly excellent in preventing and improving the aging phenomenon of skin and the like.

  The extract of Itohimehae used in the present invention is extracted using the root of Itohimehagi, which is a plant belonging to the human family, but can also be extracted using the above-mentioned genus plant.

  The Clara extract used in the present invention is extracted by using the roots of the leguminous plant Clara, but can be extracted by using the above-mentioned part and a plant belonging to the same genus.

  The peony extract used in the present invention is extracted using a peony root that has been removed from the peony root, but can be extracted from the above-ground part and a plant belonging to the same genus.

  The oyster extract used in the present invention is extracted using oyster leaves of a cynoaceae plant, but can be extracted using the above-mentioned part and a genus plant.

The tanjin extract used in the present invention is extracted using roots of tannins of Labiatae plants, but can be extracted using the above-ground parts and the same genus plants.

  The centella extract used in the present invention is extracted by using the whole plant of the celery family plant, but it can be extracted by using a plant belonging to the same genus.

  The puer extract used in the present invention is extracted by using a so-called puer leaf obtained by post-fermenting tea leaves of a camellia plant with black koji mold or the like.

  In the present invention, plant extracts such as Itohime extract, Clara extract, peony extract, oyster extract, tanjin extract, camellia extract, puer extract, etc. Alternatively, it can be used after being crushed or crushed. Furthermore, the extract obtained by extracting these with a solvent, and the non-volatile content obtained by evaporating or lyophilizing the extraction solvent from the extract can be used.

  Examples of the extraction solvent used here include water, methanol, ethanol, ethylene glycol, propylene glycol, lower alcohols such as 1,3-butylene glycol, ketones such as acetone, esters such as ethyl acetate, and ethyl ether. Various solvents, such as ethers and aromatics, such as toluene, are mentioned, It can use individually or in combination of 2 or more types.

  Arbutin used in the present invention is a natural type (β-glucoside type) glycoside contained in plants such as cowberry, walrus, and pear, and has a chemical name of 4-hydroxyphenyl-β-D-glucosipyrano. Sid's can be used.

  Ascorbic acid used in the present invention is a water-soluble vitamin contained in citrus fruits such as mandarin orange and lemon, fruits and vegetables such as kiwi, strawberry and melon, and is also called vitamin C. Furthermore, in the present invention, derivatized products such as mono- or diesters with palmitic acid and stearic acid, and ascorbic acid derivatives such as magnesium phosphate, sodium salt or glycoside can also be used.

  As the alginate oligosaccharide used in the present invention, a polymer alginate or a polymer alginate (sodium salt, magnesium salt, potassium salt, etc.) having a reduced molecular weight and a molecular weight of 2000 to 20000 is used. The decomposition method may be acid or alkali decomposition, enzymatic decomposition, thermal decomposition, etc., regardless of the method, and after converting high molecular alginic acid to low molecular alginic acid, low molecular alginate is used. But it ’s okay.

  The plant extract used in the present invention is generally used as a component of medicines or folk medicines, foods and cosmetics, and its safety has been confirmed.

  The fibroblast proliferation promoter of the present invention contains one or more selected from the plant extract, arbutin, ascorbic acid, and alginic acid oligosaccharides, and the total amount added to the fibroblast proliferation promoter is the agent. Depending on the type, the evaporation residue may be used as it is, the blending amount may be adjusted as appropriate according to the intended use, and the amount of the fibroblast proliferation promoter of the present invention is particularly used. There is no restriction | limiting, It can adjust suitably with a use or application.

The fibroblast proliferation promoter of the present invention can be applied to various forms such as external use, internal use, and treatment of raw materials. In addition, it can be used in combination with a drug used in normal treatment for external or internal use, etc., and the combined drug makes it easier to express the effect of the present invention.
The fibroblast growth-promoting agent of the present invention is a pharmaceutical, quasi-drug, topical or systemic skin cosmetic, various external preparations for skin, such as medicinal or cosmetic preparations applied to the scalp / hair, for bath It can mix | blend with an agent, food-drinks, etc.

  The skin external preparation, bath preparation, and food and drink of the present invention contain one or more fibroblast proliferation promoters. The total blending amount of the fibroblast proliferation promoter into the external preparation for skin and the like varies depending on the dosage form, but generally, the fiber for the external preparation for skin, the bath preparation, and the total food and drink is the fiber. In terms of the amount of plant extract, arbutin, ascorbic acid, alginate oligosaccharide contained in the blast promoter, 0.01% by mass to 10% by mass, preferably 0.025% by mass to 5% by mass, If it specifies, it is desirable to contain so that it may become 0.05 mass%-2.5 mass%.

  The skin external preparation and bath preparation of the present invention include, in addition to the fibroblast proliferation promoter, known functional ingredients conventionally used in normal skin external preparations or bath preparations, such as moisturizers and emollients. , Blood circulation promoters, cell activators, antioxidants, anti-inflammatory agents, antibacterial agents, peroxide inhibitors and the like can be blended.

More specifically, known functional ingredients include humectants such as glycerin, butylene glycol, urea, and amino acids; emollients such as squalane, macadamia nut oil, olive oil, jojoba oil, and silicon oil; vitamin Es, pepper tincture, and the like. Blood circulation promoters: Cell activators such as nucleic acids, antioxidants such as dibutylhydroxytoluene (BHT), dibutylhydroxyanisole (BHA) and tocopherol acetate; anti-inflammatory agents such as glycyrrhizin and allantoin; hinokitiol, benzalkonium chloride, Various functional components such as antibacterial agents such as chlorhexidine salt and parahydroxybenzoate ester; peroxide inhibitors such as superoxide dismutase (SOD) can be blended.
In addition, various extracts derived from plants, animals, and microorganisms such as hornon extract, ginkgo biloba extract, placenta extract, and lactic acid bacteria culture extract can be added and used without limitation.

  The external preparation for skin of the present invention is an agent that can be applied externally, and there is no particular limitation on the dosage form, for example, paste, cream, gel, ointment, lotion, emulsion, pack, powder, haptic agent, etc. It can be illustrated.

  There is no restriction | limiting in particular also in the dosage form of the bath preparation of this invention, For example, liquid preparations, such as solid preparations, such as a powder and a granular form, an emulsion, and a paste form, etc. can be illustrated.

  In addition to the fibroblast proliferation promoter, various materials that are usually used in foods can be used in the food and drink of the present invention without any particular limitation.

  The dosage form of the food and drink of the present invention includes all applicable forms, for example, solid preparations such as biscuits, cookies, tablets, capsules, candy, gum, and powder, liquid preparations such as beverages, and semisolids such as jelly Examples include preparations.

  In addition, the external preparation for skin, bath preparation and food and drink of the present invention include base ingredients such as surfactants and fats and oils, and thickeners, preservatives, isotonic agents as necessary. Various additives such as an agent, an antioxidant, an ultraviolet absorber, a chelating agent, a fragrance, and a coloring agent can be used in combination.

  The surfactant is not particularly limited, and general nonionic surfactants, anionic surfactants, cationic surfactants, and amphoteric surfactants can be used. For example, alkylene oxide adduct of higher alcohol, alkylene oxide adduct of higher alkylamine, alkylene oxide adduct of higher fatty acid, alkylene oxide adduct of higher fatty acid amide, fatty acid ester of polyhydric alcohol, alkylene oxide adduct of hardened castor oil , Nonionic surfactants such as alkylene oxide adducts such as polyethylene glycol sorbitan alkyl esters and sterols; anions such as sodium alkyl sulfate, sodium alkylylmethyl taurate, sodium α-olefin sulfonate, sodium polyoxyalkylene alkyl ether sulfate Surfactants; Cationic surfactants such as alkylpyridinium chloride and distearyl dimerylammonium chloride; Sodium aminopropionate Amphoteric surfactants such as alkylpolyaminoethylglycine the like. And these surfactant can select and use 1 type (s) or 2 or more types.

  The base material component usable in the present invention is not particularly limited, and examples thereof include olive oil, camellia oil, avocado oil, macadamia nut oil, apricot oil, jojoba oil, squalane, squalene, horse oil, paraffin, and silicon. And generally known fats and oils.

  Although it does not specifically limit as a thickener which can be used in this invention, For example, polyvinyl alcohol, polyvinyl acrylamide, polyethyleneglycol, and these various derivatives; Celluloses, such as a hydroxyalkyl cellulose, and its derivative; Dextran, Examples include gums such as gelatin, gum arabic, and gum tragacanth; and water-soluble polymers such as carboxyvinyl polymer.

  Examples of the preservative that can be used in the present invention include, but are not limited to, parahydroxybenzoic acid esters, paraoxybenzoates and their derivatives, phenoxyethanol, hinokitiol, benzalkonium chloride, chlorhexidine salts, and the like. .

  The isotonic agent that can be used in the present invention is not particularly limited, and examples thereof include inorganic salts such as sodium chloride, potassium chloride, and calcium chloride.

  Although it does not specifically limit as an ultraviolet absorber which can be used in this invention, For example, a para amino benzoic acid, a benzophenone series ultraviolet absorber, a benzotriazole type ultraviolet absorber, etc. are mentioned.

  Although it does not specifically limit as a chelating agent which can be used in this invention, For example, ethylenediaminetetraacetic acid, phytic acid, a citric acid, these water-soluble salts, etc. are mentioned.

Hereinafter, the present invention will be described in more detail with reference to examples. However, the present invention is not limited to these examples.
(1) Production method of plant extract The plant extract is filtered after extracting each part of each plant shown in Table 1 below under reflux of 50% by mass ethanol aqueous solution for 1 hour, and water is extracted from the obtained extract. Ethanol was distilled off under reduced pressure to obtain each plant extract. The obtained plant extract was used for the Example shown below.

(2) Production method of alginic acid oligosaccharide 1.5 g of commercially available sodium alginate SKAT-ULV (manufactured by Kimika), 0.05 g of ammonium phosphate, 0.01 g of yeast extract, and 2 g of sodium chloride in 100 g of ion-exchanged water Dissolved and sterilized by autoclave at 2.1 atm, 121 ° C. for 20 minutes. The alginate solution after sterilization was platinized with Pseudoalteromonas halloplastic (ITM 222), which is an alginate-degrading bacterium, and precultured at room temperature for 8 hours.

  Next, 1 mL of the obtained preculture solution was ion-exchanged with sodium alginate decomposition medium (0.15 g of ammonium phosphate, 0.01 g of yeast extract, 9.0 g of sodium alginate (manufactured by Kimika), 6.0 g of sodium chloride) It was dissolved in 300 g of water and added to an autoclave that had been sterilized at 2.1 atm, 121 ° C. for 20 minutes, and then cultured with shaking at room temperature for 48 hours.

  From the sodium alginate decomposition solution after shaking culture, a centrifugal separation operation (10000 rpm × 10 minutes) was performed to remove the cells, and a supernatant was obtained. Add the same amount of methanol to the resulting supernatant, precipitate high molecular weight (tens of thousands) sodium alginate from the decomposed sodium alginate solution, and filter and contain low molecular weight sodium alginate oligosaccharides. A filtrate was obtained.

  To remove impurities such as sodium chloride from the filtrate containing sodium alginate oligosaccharide and perform purification, gel filtration operation (Sephadex LH-20, Pharmacia Fine Chemicals) was performed. After the gel filtration operation, the obtained liquid was concentrated and dried with a freeze dryer to obtain 5.4 g (yield 60%) of the desired sodium alginate oligosaccharide (weight average molecular weight: about 2000).

In addition, the alginate oligosaccharide sodium having a weight average molecular weight of about 20000 was obtained in the same manner as described above except that the shaking culture time was changed from 48 hours to 8 hours.
Further, the obtained sodium alginate oligosaccharide having a weight average molecular weight of about 2000 is operated together with an ion exchange resin (Amberlite 1006F H, manufactured by Rohm and Haas Japan) to obtain an alginate oligosaccharide having a weight average molecular weight of about 2000. Got.

  The weight average molecular weight was measured using an aqueous gel permeation chromatography apparatus GPC-8020 (manufactured by Tosoh Corporation). The measurement conditions were such that G3000 (manufactured by Tosoh Corp.) and G5000 (manufactured by Tosoh Corp.) were directly connected to the column, the column temperature was 40 ° C., the column flow rate was 1.0 ml / min, the eluent 0.1M NaCl aqueous solution, RI detection, and the weight average molecular weight is a value obtained by converting PEG (polyethylene glycol) as a standard.

  The obtained sodium alginate oligosaccharide and alginate oligosaccharide were used in the following examples.

(3) Arbutin Arbutin manufactured by Wako Pure Chemical Industries, Ltd. was used in the following examples.
(4) Ascorbic acid L (+)-ascorbic acid manufactured by Wako Pure Chemical Industries, Ltd. was used in the examples shown below.

(I) Fibroblast proliferation promoter [Example 1]
Arbutin was adjusted to 10 mg / mL, and then sterilized using a 0.2 μm syringe filter in a clean bench. Then, sterilized purified water was added to adjust to 2 mg / mL to prepare a diluted solution of arbutin to be added to the medium.
Next, normal human dermal fibroblasts manufactured by Kurashiki Boseki Co., Ltd. were differentiated and cultured according to a prescribed preparation method. The medium used was a low serum medium (Medium 106S) for normal human skin fibroblast proliferation supplemented with a low serum growth additive (LSGS).
The medium was seeded with a solution of normal human adult fibroblasts (500000 cells / mL), placed in a humidified incubator at 37 ° C., 5% -CO ₂ , the medium was changed every other day, and cultured for 6 days.
Six days later, cells were peeled from the petri dish to prepare a cell suspension (15000 cell / mL). 1 mL of the cell suspension was seeded on a 24-well plate and cultured for 2 days. At the time of medium exchange, 10 μL of the diluted arbutin solution (final concentration becomes 20 μg / mL) was added, and further cultured for 2 days. The medium was changed every two days, and the medium was collected on the 8th day after cell seeding. Then, the cells were peeled off with 1 mol / L sodium hydroxide, and the amount of protein was measured by the Lowry method.

  The amount of the protein at this time was 125 when compared with the amount of the protein of Comparative Example 1 in which sterilized purified water was added instead of the diluted solution of the fibroblast growth promoting component (arbutin) and the other operations were the same. %, An increase of 25%. This protein is derived from fibroblasts and serves as an index of cell proliferation, and an increase in the amount of protein reflects the proliferation of fibroblasts.

[Examples 2 to 40]
The amount of protein obtained by the same operation as in Example 1 except that the fibroblast growth promoting component and the added final concentration were changed as shown in Table 2 were compared with the amount of protein in Comparative Example 1. The results are shown in Table 2.

  As shown in Table 2, those using one or more compositions selected from the various plant extracts of Examples 1 to 40, arbutin, ascorbic acid, and alginate oligosaccharides as the fibroblast proliferation promoting component are as follows: It can be seen that the effect of promoting the proliferation of fibroblasts is significant.

(II) Formulation example of external preparation for skin Formulation of external preparation for skin (skin lotion, milky lotion, cream, body cream) formulated with a fibroblast growth promoter with the composition shown in Tables 3-14 was prepared. The preparation method is as follows. The unit of the blending amount is g, and the “remaining amount” of purified water in the table is an amount that makes the total amount 100 g.

Lotion (Examples 41-62, Comparative Example 2)
Each of A component and B component of Tables 3-5 was heated and melt | dissolved at 80 degreeC, and B component was gradually added and emulsified to A component, stirring. Thereafter, the mixture was cooled with stirring, C component was added at 40 ° C, and the preparation was completed at 35 ° C.

Latex (Examples 63 to 84, Comparative Example 3)
Each of D component and E component of Tables 6-8 was heated and melt | dissolved at 80 degreeC, and D component was added to E component, stirring, and after making it uniform, it emulsified with the homomixer. The mixture was cooled while stirring with a handle mixer, and the F component was added at 40 ° C. or lower to complete the preparation.

Cream (Examples 85-106, Comparative Example 4)
The G component and the H component in Tables 9 to 11 were each dissolved by heating to 75 ° C., and the H component was added little by little while stirring the G component with a paddle mixer. Then, it cooled, stirring, and added I component at 40 degreeC, Then, preparation was complete | finished at about 35 degreeC.

Body cream (Examples 107 to 128, Comparative Example 5)
The J component and the K component in Tables 12 to 14 were each heated to 75 ° C., and the K component was added little by little while stirring the J component with a paddle mixer. Then, it cooled, stirring, and added L component at 45 degrees C or less, and complete | finished preparation.

Evaluation About the external preparations for skin of Examples 41 to 128 and Comparative Examples 2 to 5, appropriate amounts were given twice a day in the morning and at night for a total of 184 people each (2 groups of 23 women x 4). A monitor test was conducted in which application to the skin was continued for one month, and the feeling of use was examined. Table 15 shows the results of evaluation based on the following criteria. None of the patients complained of skin abnormalities during the period of use.
Effective: Skin elasticity, gloss, elasticity increased slightly Effective: Skin elasticity, gloss, elasticity increased slightly No effect: No change from before use

  In the skin external preparations of Examples 41 to 128 containing the fibroblast proliferation promoter of the present invention, the firmness, gloss and elasticity of the skin increased due to the fibroblast proliferation promoting effect. On the other hand, in the external preparations for skin of Comparative Examples 2 to 5 to which the fibroblast proliferation promoter of the present invention was not added, the firmness, gloss and elasticity of the skin were not changed from before use. All external preparations for skin can improve the aging phenomenon of the skin.

(III) Formulation of external preparation for skin (head hair) Next, prescription of external preparation for skin (hair) (shampoo, conditioner, hair tonic) blended with a fibroblast growth promoter with the composition shown in Tables 16-18. Prepared. The preparation method is as follows. The unit of the blending amount is g, and the “remaining amount” of purified water in the table is an amount that makes the total amount 100 g.

Shampoo (Examples 129 to 150, Comparative Example 6)
The M components in Tables 16 to 18 were heated to 75 ° C and cooled to 35 ° C while stirring. Then, N component was added, continuing stirring, and pH adjustment and viscosity adjustment were performed. Further, O component was added to complete the preparation.

Conditioner (Examples 151-172, Comparative Example 7)
P component and Q component of Tables 19-21 were each heated to 75 degreeC, and Q component was added little by little, stirring P component with a paddle mixer. Then, it cooled, stirring with a paddle mixer, and R component was added at 45 degrees C or less, and preparation was completed.

Hair tonic (Examples 173 to 194, Comparative Example 8)
All of the S component, the T component, and the U component in Tables 22 to 24 were warmed to 40 ° C. and mixed.

Evaluation With regard to the external preparations for skin (hair) of Examples 129 to 194 and Comparative Examples 6 to 8, 138 shampoos and conditioners were used daily for each of 138 people (23 groups × 3 prescriptions) for one male and one female. Use a suitable amount for hair as a hair washing or conditioning agent during bathing, and use a suitable amount for hair tonic after daily bathing or in the morning on the scalp or hair, and conduct a monitoring test for one month to examine the feeling of use. It was. Table 25 shows the results of evaluation based on the following criteria. None of the patients complained of skin abnormalities during the period of use.
Effective: Scalp firmness, gloss, elasticity increased or hair became healthy Slightly effective: Scalp elasticity, gloss, elasticity increased slightly or hair became slightly healthy No effect: No change from before use

  In the external preparation for skin (head hair) of Examples 129 to 194 formulated with the fibroblast proliferation promoter of the present invention, the scalp was increased or slightly increased in elasticity, gloss, elasticity, and the hair became healthy or Slightly healthy and improved aging due to the effect of promoting fibroblast proliferation was observed. On the other hand, in the external preparations for skin (hair) of Comparative Examples 6 to 8, since the scalp or the hair was evaluated before use and no change, the effects of the external preparation for skin (hair) of the present invention are all. It was significant.

(IV) Formulation of external preparation for skin (nail) Next, a formulation of external preparation for skin (nail) (treatment cream for nail) containing a fibroblast proliferation promoter with the composition shown in Tables 26 to 28 was prepared. . The preparation method is as follows. The unit of the blending amount is g, and the “remaining amount” of purified water in the table is an amount that makes the total amount 100 g.

Nail treatment cream (Examples 195 to 216, Comparative Example 9)
Both V component and W component of Tables 26 to 28 were dissolved by heating at 80 ° C., and the W component was added and emulsified while stirring the V component with a homomixer. After emulsification, the X component was added and stirred until uniform, then the Y component was further added and stirred and mixed. Then, it stirred until it became 40 degreeC, cooling, added Z component, and complete | finished preparation at 35 degreeC.

Evaluation Regarding the external preparations for skin (nails) of Examples 195 to 216 and Comparative Example 9, the appropriate amount of the above nail treatment cream is provided around the nails for 69 women (3 groups) each (23 groups). A monitor test was carried out to continue application for one month, and the feeling of use was examined. Table 29 shows the results of evaluation based on the following criteria. None of the patients complained of skin abnormalities during the period of use.
Effective: Increased gloss / elasticity of nails Slightly effective: Increased gloss / elasticity of nails No effect: No change before use

  In the external preparation for skin (nail) of Examples 195 to 216, in which the fibroblast proliferation promoter of the present invention is blended, it is an evaluation result that the gloss / elasticity of the nail is increased or slightly increased, and the fibroblast proliferation promotion The improvement of the aging phenomenon by the effect was recognized. On the other hand, in the external preparation for skin (nail) of Comparative Example 9, since the gloss and elasticity of the nail were evaluated before use and no change, the effects of the external preparation for skin (nail) of the present invention were all It was significant.

(V) Formulation examples of bath preparations Formulations of bath preparations (bathing agents, body soaps) containing fibroblast proliferation promoters having the compositions shown in Tables 30 to 32 and Tables 34 to 36 were prepared. The preparation method is as follows. The unit of the blending amount is g, and the “remaining amount” of purified water in the table is an amount that makes the total amount 100 g.

Bath agent (Examples 217 to 238, Comparative Example 10)
The AA component and the AB component in Tables 30 to 32 were mixed until they were uniform, then the AA component and the AB component were mixed, and mixed well until they became more uniform.

Evaluation Regarding the bathing agents of Examples 217 to 238 and Comparative Example 10 above, a total of 46 people (one group of 23) each for males and females were bathed by dissolving 30 mL of bathing agent in 180 L of hot water during daily bathing. A monitoring test was conducted for one month, and the feeling of use was examined. Table 33 shows the results of the evaluation based on the following criteria. None of the patients complained of skin abnormalities during the period of use.
Effective: Skin elasticity, gloss, elasticity increased slightly Effective: Skin elasticity, gloss, elasticity increased slightly No effect: No change from before use

  The bathing agents of Examples 217 to 238 containing the fibroblast proliferation promoter of the present invention are the results of evaluation that the firmness, gloss, and elasticity of the skin are increased or slightly increased, and aging due to the fibroblast proliferation promoting effect An improvement in the phenomenon was observed. On the other hand, the effects of the bathing agent of the present invention were significant in the bathing agent of Comparative Example 10 because the skin firmness, glossiness and elasticity were evaluated before use and unchanged.

Body soap (Examples 239 to 260, Comparative Example 11)
The AC components in Tables 34 to 36 were heated to 80 ° C. to make soap, and then AD components were sequentially added and dissolved. Then, AE component was added at 40 degreeC, cooling, and preparation was complete | finished at 35 degreeC.

Evaluation With respect to the body soaps of Examples 239 to 260 and Comparative Example 11, 3 women each (23 groups), a total of 69 people, used a proper amount as a body soap during daily bathing for 1 month. A continuous monitor test was conducted to examine its feeling of use.
Table 37 shows the results of evaluation based on the following criteria. None of the patients complained of skin abnormalities during the period of use.
Effective: Skin elasticity, gloss, elasticity increased slightly Effective: Skin elasticity, gloss, elasticity increased slightly No effect: No change from before use

  In the body soaps of Examples 239 to 260 containing the fibroblast proliferation promoter of the present invention, the evaluation results show that the firmness, gloss and elasticity of the skin are increased or slightly increased, and aging due to the effect of promoting fibroblast proliferation An improvement in the phenomenon was observed. On the other hand, the effects of the bathing agent of the present invention were significant in the bathing agent of Comparative Example 11 because the skin firmness, glossiness and elasticity were evaluated before use and unchanged.

(VI) Formulation example of foods and drinks Next, foods and beverages (bread and supplements (tablets)) formulated with a fibroblast growth promoter with the compositions shown in Tables 38 to 41 were prepared. The preparation method is as follows. The unit of the blending amount is g, and the “remaining amount” of water in the table is an amount that makes the total amount 100 g.

Bread (Examples 261 to 270, Comparative Example 12)
A mixture of all the AF components in Tables 38 to 39 was added to the mixture of the AG component and AH component heated to 40 ° C. and kneaded well when the mixture became uniform. Primary fermentation was carried out at 35 ° C. for 40 minutes, and kneaded again so as to remove air. After secondary fermentation at 40 ° C. for 40 minutes, it was baked at 180 ° C. for 25 minutes.

Supplement (Tablet) (Examples 271 to 280, Comparative Example 13)
The well-mixed AI component and AJ component in Tables 40 to 41 were pressed into a tablet using a tableting machine to form tablets (0.3 g).

Evaluation Regarding the foods and drinks of Examples 261 to 280 and Comparative Examples 12 and 13, a total of 44 women each (11 groups × 2 prescriptions), with regard to bread, at the time of daily breakfast For supplements (tablets) in which about 90 g of the bread of the example or comparative example is consumed as a staple food, a normal life is taken except for taking 5 tablets (1.5 g) of supplements (tablets) after 3 meals daily. A monthly monitor test was conducted to examine the feeling of use.
Table 42 shows the results of evaluation based on the following criteria. None of the patients complained of skin abnormalities during the period of use.
Effective: Skin elasticity, gloss, elasticity increased slightly Effective: Skin elasticity, gloss, elasticity increased slightly No effect: No change from before use

  In the monitor which ingested the food and drink of Examples 261-280 which mix | blended the fibroblast proliferation promoter of this invention, it is an evaluation result that the firmness, luster, elasticity of skin increases or slightly increases, and fibroblast proliferation The aging phenomenon was improved by the promoting effect. On the other hand, in the monitor which ingested the food / beverage of the comparative example 12 or 13, since the elasticity, luster, and elasticity of skin were evaluation before use and a change, all the effects of the food / beverage of this invention are significant. there were.

  Cypress extract, Clara extract, Peonies extract, Oyster extract, Tanjin extract, Clover extract, Pual extract, Arbutin, Ascorbic acid or Alginate oligosaccharides are used to promote collagen growth in fibroblasts and The amount of hyaluronic acid is relatively increased, and as a result, wrinkles and tarmi are prevented, alleviated and improved, so various external preparations for skin including cosmetics aimed at preventing and improving the aging phenomenon, It can be used for bath preparation, food and drink.

Claims (5)

  Fibroblast proliferation characterized by containing one or more selected from Itohimehagi extract, Clara extract, Peonies extract, Oyster extract, Tanjin extract, Clover extract, Puaru extract, Arbutin, Ascorbic acid and Alginate oligosaccharide Accelerator.   An external preparation for skin comprising the fibroblast growth promoter according to claim 1.   A bath preparation comprising the fibroblast growth promoter according to claim 1.   A food or drink comprising the fibroblast growth promoter according to claim 1.   Contains 0.01% by mass to 10% by mass of one or more selected from Itohimeha extract, Clara extract, peonies extract, oyster extract, tanjin extract, cinnamon extract, puer extract, arbutin, ascorbic acid and alginate oligosaccharides The skin external preparation, bath preparation, or food and drink according to claim 2.