CN111818903A

CN111818903A - Cosmetic or medical material

Info

Publication number: CN111818903A
Application number: CN201980006864.5A
Authority: CN
Inventors: 青木贵裕; 川岛知子; 谷池优子
Original assignee: Panasonic Intellectual Property Management Co Ltd
Current assignee: Panasonic Intellectual Property Management Co Ltd
Priority date: 2018-03-05
Filing date: 2019-02-01
Publication date: 2020-10-23
Anticipated expiration: 2039-02-01
Also published as: CN111818903B; JPWO2019171843A1; WO2019171843A1

Abstract

The cosmetic or medical material according to the present disclosure, which enables efficient percutaneous absorption of an active ingredient, comprises a 1 st cyclic compound or a salt thereof represented by formula (1), a 2 nd cyclic compound or a salt thereof as an active ingredient, and a biocompatible film, (wherein in formula (1), X represents CH, N, or CH₂Or NH, the number of adjacent atoms is 1-6, R is a saturated bond or an unsaturated bond₁Is at least one of carboxyl and hydroxyl, R₂Is at least one member selected from the group consisting of an acrylic group, an isopropyl group, a methoxy group, an aldehyde group, a methyl group, a hydroxymethyl group and a hydrogen atom, m is an integer of 1 or more, n is an integer of 0 or more, and the sum of m and n is 10 or less).

Description

Cosmetic or medical material

Technical Field

The present disclosure relates to a cosmetic or medical material.

Background

In the cosmetic field, the pharmaceutical field, and the like, a procedure is performed in which an active ingredient is absorbed from a living body such as skin, that is, transdermally absorbed, to produce a cosmetic effect, a therapeutic effect for a disease, or a preventive effect for a disease. For example, ascorbic acid has an action of inhibiting loss of collagen associated with wrinkles, production of melanin (melanin) which becomes a sunburn or a spot, and reducing melanin, and therefore, if ascorbic acid is allowed to penetrate into the lower layer of the epidermis of the skin where melanin is produced, it exerts an effect of preventing or treating sunburn.

However, ascorbic acid is a water-soluble substance and is not easily permeated from the hydrophobic skin surface into the skin. Therefore, a combination of vitamin B6 and B3, niacinamide, and other agents for promoting the absorption of ascorbic acid into the skin has been proposed. For example, patent documents 1 to 3 disclose an external composition containing a substance having a cosmetic effect such as ascorbic acid and an accelerator for accelerating the absorption of ascorbic acid or the like into the skin.

Documents of the prior art

Patent document

Patent document 1: japanese laid-open patent publication No. 6-107531

Patent document 2: japanese patent laid-open No. 2006-45140

Patent document 3: japanese patent laid-open publication No. 2007-509899

Disclosure of Invention

Problems to be solved by the invention

In addition to ascorbic acid, cosmetics and medical materials capable of efficiently absorbing active ingredients in living bodies such as skin are required. Disclosed is a cosmetic or medical material which enables efficient percutaneous absorption of an active ingredient in the cosmetic field, the medical field, and the like.

Means for solving the problems

The cosmetic or medical material of the present disclosure includes a 1 st cyclic compound represented by the following formula (1) or a salt thereof, a 2 nd cyclic compound or a salt thereof as an active ingredient, and a biocompatible film. (in the formula (1), X is CH, N, CH₂Or NH, the number of adjacent atoms is 1-6, R is a saturated bond or an unsaturated bond₁Is at least one of carboxyl and hydroxyl, R₂Is at least one member selected from the group consisting of an acrylic group, an isopropyl group, a methoxy group, an aldehyde group, a methyl group, a hydroxymethyl group and a hydrogen atom, m is an integer of 1 or more, n is an integer of 0 or more, and the sum of m and n is 10 or less),

ADVANTAGEOUS EFFECTS OF INVENTION

According to the present disclosure, a cosmetic or medical material capable of efficiently transdermally absorbing an active ingredient in the cosmetic field, the medical field, and the like can be obtained.

Detailed Description

The present inventors have studied in detail the combination of an active ingredient and a percutaneous absorption enhancer in the cosmetic field, the pharmaceutical field, and the like, which can efficiently carry out percutaneous absorption. As a result, it was found that, when both the active ingredient and the accelerator are cyclic compounds, the effect of improving the percutaneous absorbability by the addition of the accelerator can be effectively improved by causing charge transfer between the cyclic compounds, interaction such as hydrogen bonding, or the like. The outline of the cosmetic or medical material of the present disclosure is as follows.

The cosmetic or medical material of the present disclosure includes a 1 st cyclic compound represented by the following formula (1) or a salt thereof, a 2 nd cyclic compound or a salt thereof as an active ingredient, and a biocompatible film.

(in the formula (1), X is CH, N, CH₂Or NH, the number of adjacent atoms is 1-6, R is a saturated bond or an unsaturated bond₁Is at least one of carboxyl and hydroxyl, R₂Is at least one member selected from the group consisting of an acrylic group, an isopropyl group, a methoxy group, an aldehyde group, a methyl group, a hydroxymethyl group and a hydrogen atom, m is an integer of 1 or more, n is an integer of 0 or more, and the sum of m and n is 10 or less)

The cosmetic or medical material of the present disclosure will be described in detail below.

(constitution of cosmetic Material or medical Material)

The cosmetic or medical material of the present disclosure comprises a percutaneous absorption enhancer, an active ingredient, and a biocompatible film. Hereinafter, each constituent element will be described in detail. When the active ingredient of a cosmetic is contained, it may be referred to as a cosmetic, and when the active ingredient of a pharmaceutical is contained, it may be referred to as a medical material. In addition, the cosmetics and medical materials of the present disclosure also include quasi-drugs classified into cosmetics and drugs.

(1) Percutaneous absorption promoter

The percutaneous absorption enhancer is a preparation that enhances the amount of a desired component that permeates into the skin. The percutaneous absorption enhancer of the present application is a cyclic compound represented by the formula (1). Hereinafter, a cyclic compound as a percutaneous absorption enhancer is referred to as a 1 st cyclic compound. As described later, the compound which is an active ingredient in the cosmetic field, the pharmaceutical field, and the like to which the present application is directed is also a cyclic compound (hereinafter referred to as a 2 nd cyclic compound). Therefore, the 1 st cyclic compound and the 2 nd cyclic compound are likely to interact with each other, and both the 1 st cyclic compound and the 2 nd cyclic compound are likely to permeate into the skin, whereby the percutaneous absorption promoting effect of the 2 nd cyclic compound can be improved.

At least one of the 1 st ring compound and the 2 nd ring compound is desirably an aromatic compound, and more desirably both the 1 st ring compound and the 2 nd ring compound are aromatic compounds. Since at least one of the 1 st ring compound and the 2 nd ring compound is an aromatic compound, the interaction between the 1 st ring compound and the 2 nd ring compound is more likely to occur due to the interaction derived from an aromatic ring, and both the 1 st ring compound and the 2 nd ring compound are likely to permeate into the skin.

Further, it is desirable that at least one of the 1 st ring compound and the 2 nd ring compound contains a hydroxyl group, a carboxyl group, or both. By including a hydroxyl group and a carboxyl group, the interaction between the 1 st cyclic compound and the 2 nd cyclic compound can utilize hydrogen bonds or the like, and the 2 nd cyclic compound is more likely to interact and permeate into the skin.

The 1 st cyclic compound is specifically a cyclic compound represented by the following formula (1) or a salt thereof.

In the formula (1), X is CH, N, CH₂Or NH, the number of adjacent atoms is 1-6, R is a saturated bond or an unsaturated bond₁Is at least one of carboxyl and hydroxyl, R₂Is at least one member selected from the group consisting of an acrylic group, an isopropyl group, a methoxy group, an aldehyde group, a methyl group, a hydroxymethyl group and a hydrogen atom, m is an integer of 1 or more, n is an integer of 0 or more, and the sum of m and n is 10 or less.

In the formula (1), m is 2 or more, i.e., R₁In the case where there are 2 or more, R₁Each independently is a carboxyl group or a hydroxyl group.

In the formula (1), n is 2 or more, that is, R₂In the case where there are 2 or more, R₂Each independently is an acrylic group, an isopropyl group, a methoxy group, an aldehyde group, a methyl group, a hydroxymethyl group or a hydrogen atom.

The salt of the 1 st cyclic compound includes a salt of an anion whose proton is removed from the carboxyl group or the hydroxyl group of the 1 st cyclic compound and an arbitrary 1-valent or polyvalent cation, or a hydrochloride when X is NH.

The 1 st cyclic compound represented by the formula (1) or a salt thereof is, for example, at least 1 selected from nicotinic acid, sodium nicotinate, vanillic acid, sodium vanillic oxalate, gallic acid, ferulic acid, sodium ferulate, pyridoxal hydrochloride, menthol, pyromellitic acid, mellitic acid, trimellitic acid, hydroxybenzoic acid, dihydroxybenzoic acid, hydroxyisophthalic acid, isovanillic acid, syringic acid, anisic acid, methoxysalicylic acid, trimethoxybenzoic acid, phloroglucinol, methoxycatechol, resorcinol, pyrogallol, methoxyhydroquinone, syringic acid, and methylphthalic acid, vanillin.

In cosmetics or medical materials, the percutaneous absorption enhancer may include only 1 of the 1 st cyclic compounds, or may include 2 or more.

The molecular weight of the 1 st cyclic compound or a salt thereof is desirably 94 or more and 500 or less. When the molecular weight is 500 or less, the size of the molecule or ion of the 1 st cyclic compound becomes small, and the 1 st cyclic compound easily permeates into the skin. The 1 st cyclic compound or a salt thereof is desirably more hydrophobic than the 2 nd cyclic compound described later. As described above, by making the hydrophobicity of the 1 st cyclic compound higher than that of the 2 nd cyclic compound as an active ingredient, the complex formed by the interaction between the 1 st cyclic compound and the 2 nd cyclic compound has a hydrophobicity higher than that of the 2 nd cyclic compound, and the permeability to the skin is improved.

The hydrophobicity of the 1 st cyclic compound can be evaluated by, for example, a partition coefficient. What is needed isThe partition coefficient is an actual measurement value of the equilibrium solubility ratio in the case where the compound is dissolved in a two-phase of water and n-octanol, and is represented by the partition coefficient P log₁₀(concentration of compound in n-octanol)/(concentration of compound in water)) was calculated. The larger the partition coefficient P, the higher the hydrophobicity (or lipid solubility) of the compound. In addition, in the case where the compound is more soluble in water than n-octanol, the partition coefficient takes a negative value.

The partition coefficient of the 1 st cyclic compound is desirably 0 or more. More preferably, it is 0 or more and 4.0 or less. When the partition coefficient is 0 or more, the 1 st cyclic compound can permeate into the skin, and when a complex is formed with the 2 nd cyclic compound, the complex can be absorbed into the skin more than when the 2 nd cyclic compound is used alone as an active ingredient. When the partition coefficient is more than 4.0, the 1 st cyclic compound may have too high hydrophobicity to easily permeate into the skin.

(2) Active ingredient

As described above, the active ingredient to be the subject of the present application is the 2 nd cyclic compound or a salt thereof. From this, it is considered that the 1 st ring compound and the 2 nd ring compound are likely to interact with each other due to, for example, a small steric hindrance between them, and both the 1 st ring compound and the 2 nd ring compound are likely to permeate into the skin.

As described above, the 2 nd cyclic compound is also desirably an aromatic compound. Further, it is desirable that the 2 nd cyclic compound contains a hydroxyl group, a carboxyl group, or both. The salt of the 2 nd cyclic compound includes a salt of an anion whose proton is removed from the carboxyl group or the hydroxyl group of the 2 nd cyclic compound and an arbitrary cation having a valence of 1 or more.

The cosmetic effect by the 2 nd cyclic compound may be, for example, whitening, anti-wrinkle, UV blocking, moisturizing, and the like. Examples of cosmetic ingredients satisfying such conditions include vitamins such as vitamin A including retinol, Retinal (Retinal), retinoic acid, and the like, thiamine, riboflavin, vitamin B including pyridoxine, pyridoxamine, folic acid, vitamin D including ergocalciferol, cholecalciferol, vitamin E including alpha-tocopherol, vitamin K including phylloquinone and menadione, vitamin A derivatives such as retinoic acid and palmitic acid, ascorbyl glyceride, magnesium L-ascorbyl-2-phosphate, vitamin C derivatives such as ascorbyl glucoside, alpha-tocopherol acetate, alpha-tocopheryl quinone, vitamin E derivatives such as tocopheryl phosphate, tranexamic acid, arbutin, hydroquinone, kojic acid, 4-methoxysalicylic acid potassium, 4-n-butylresorcinol (resveratrol, rucinol), Flavonols such as ellagic acid, gossypol, myricetin, and rutin, and amino acids such as proline, phenylalanine, tryptophan, tyrosine, and histidine. The 2 nd cyclic compound may have a medical effect such as analgesia, vasodilation, angina pectoris therapy, asthma therapy, or the like. Examples of the medical component satisfying such conditions include acetylsalicylic acid, tiaramide hydrochloride, acetaminophen, hydrocortisone, prednisolone, triamcinolone, dexamethasone, betamethasone, minoxidil, finasteride, stephanine, isosorbide mononitrate, isosorbide dinitrate, bisoprolol, estrone, estradiol, and estriol.

In the case where the cosmetic or medical material of the present disclosure is used as a cosmetic or medical material that mainly exerts whitening and the like effects, the 2 nd cyclic compound preferably contains at least 1 selected from ascorbic acid, sodium ascorbate, arbutin, and ellagic acid.

The active ingredient used in the present disclosure may include 1 of these 2 nd cyclic compounds, or may include 2 or more of the same use or 2 or more of different uses. Further, these 2 nd cyclic compounds may be salts, hydrochlorides, and the like.

The molecular weight of the 2 nd cyclic compound or a salt thereof is desirably 4000 or less. When the molecular weight is 4000 or less, the size of the molecule or ion of the 2 nd cyclic compound becomes small, and the 2 nd cyclic compound easily permeates into the skin. Further, the molecular weight of the 2 nd cyclic compound or a salt thereof is more desirably 500 or less. In the case of a molecular weight of 500 or less, the size of the molecule or ion of the 2 nd cyclic compound is smaller, and the 2 nd cyclic compound is more likely to permeate into the skin.

As described above, the 1 st cyclic compound is desired to have higher hydrophobicity than the 2 nd cyclic compound or a salt thereof. Thus, when the 1 st cyclic compound is used as a percutaneous absorption enhancer, the hydrophobicity of the complex of the 1 st cyclic compound and the 2 nd cyclic compound is increased as compared with that of the 2 nd cyclic compound monomer, and the 2 nd cyclic compound is easily absorbed through the skin.

In particular, when the partition coefficient of the 2 nd cyclic compound is less than 0, the 2 nd cyclic compound alone is not easily absorbed through the skin. When such a 2 nd cyclic compound having a partition coefficient of less than 0 is used, the percutaneous absorption promoting effect by the 1 st cyclic compound acts more effectively, and the absorption into the skin can be improved. Examples of the 2 nd cyclic compound having a partition coefficient of less than 0 include riboflavin, pyridoxine, pyridoxamine, folic acid, ascorbyl glyceride, magnesium L-ascorbyl-2-phosphate, ascorbyl glucoside, 3-O-methyl-L-ascorbic acid, tocopheryl phosphate, arbutin, kojic acid, proline, phenylalanine, tryptophan, tyrosine, histidine, rutin, isosorbide mononitrate, and the like.

Ascorbic acid is known to have an effect on, for example, spots, wrinkles, and the like. Although the molecular weight of ascorbic acid is 200 or less, the partition coefficient is considered to be-1.85. Thus, ascorbic acid generally has low skin permeability. In the case of using ascorbic acid as the 2 nd cyclic compound of the cosmetic or medical material of the present disclosure, as described in the following examples, if the 1 st cyclic compound is used, the absorption into the skin is improved as compared with the case of using it alone.

(3) Biocompatible membranes

The biocompatible membrane is capable of retaining at least one of a 1 st cyclic compound or a salt thereof, and a 2 nd cyclic compound or a salt thereof. Biocompatibility is desired for bringing the biocompatible film into contact with or adhering to the skin or the like. The term "biocompatible" means that a living body such as the skin is less likely to develop redness or macula or that redness or macula is less likely to develop in many subjects.

As will be described later, the biocompatible film can retain at least one of the 1 st cyclic compound or a salt thereof and the 2 nd cyclic compound or a salt thereof in a solid state, a state of being dissolved in an appropriate liquid, or a state of being dispersed in a gel. This makes it possible to maintain a state in which at least one of the 1 st cyclic compound and the 2 nd cyclic compound is stably in contact with a living body such as skin.

It is desirable that the biocompatible membrane be self-supporting. The self-supportability means that the form of the membrane can be maintained without any other support, and for example, when a part of the biocompatible membrane is sandwiched and lifted by a finger, tweezers, or the like, the membrane is not broken, and the whole membrane can be lifted without any support.

The material of the biocompatible membrane is preferably collagen, hyaluronic acid, polyglutamic acid, chondroitin sulfate, dermatan sulfate, keratan sulfate, heparan sulfate, heparin, chitin, chitosan, dextran, dextrin, gluten, lignin, pectin, pullulan, xanthan gum, xylan, polylactic acid, cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, carboxymethyl cellulose, methyl cellulose, ethyl cellulose, and the like, which are considered safe for living bodies. A more preferred material is regenerated cellulose. Regenerated cellulose does not have the characteristic of I-type crystals unique to natural cellulose, and therefore, it is easy to appropriately retain moisture, and can have an excellent humidity control function. Therefore, when the regenerated cellulose is worn on a living body, it is possible to retain appropriate moisture and to prevent stuffiness and rash from occurring. Further, by controlling the structure such as pores and density of the regenerated cellulose, the ability to support the 1 st and 2 nd cyclic compounds can be expected to be improved.

The raw material cellulose used for producing the biocompatible film is not particularly limited. For example, natural cellulose derived from plant species, natural cellulose derived from organisms, regenerated cellulose such as cellophane, and processed cellulose such as cellulose nanofibers can be used. Further, it is advantageous if the impurity concentration of the raw material cellulose is 10 wt% or less.

It is desirable that the biocompatible film has a thickness of 3 μm or less. When the thickness of the biocompatible film is 3 μm or less, the uncomfortable feeling is reduced when the film is placed on the skin, and the wearing property is improved. In particular, the thickness of the biocompatible film is more preferably 20nm or more and 1300nm or less. If the thickness is 1300nm or less, the biocompatible film can be attached to the skin without using an adhesive or an adhesive, an adhesive layer, or the like. This makes it possible to use cosmetics and medical materials, for example, without placing a burden on the living body and reducing stuffiness.

The biocompatible film has a size corresponding to the use of the cosmetic or medical material and the site of the skin to be used. For example, the biocompatible film can be adhered to the skin of the face, wrist, or the like. Embodiments of the present disclosure relate to biocompatible membranes typically having 7mm²The above area. If the area of the biocompatible film is 7mm²As described above, for example, a local area of the skin such as a spot can be covered to obtain a cosmetic effect. Furthermore, if a larger area of biocompatible membrane is used, a wide coverage of the skin is possible. The cosmetic or medical material of the present disclosure may be applied to living bodies other than skin, and may be applied to the surface of organs, for example, in order to improve the healing effect of the organs.

It is desirable that the ratio of the mass of the 1 st cyclic compound or a salt thereof to the total mass of the biocompatible membrane supporting the 1 st cyclic compound or a salt thereof is 0.1 or more and 50 or less by mass. When the ratio is 0.1 or more by mass, the 1 st cyclic compound can be effectively permeated into the skin by obtaining the effect of promoting percutaneous absorption of the 1 st cyclic compound. When the 1 st cyclic compound is supported on the biocompatible film at a ratio of 50 mass% or less, the biocompatible film is stably worn on the skin while maintaining high strength.

It is desirable that the ratio of the mass of the 2 nd cyclic compound or a salt thereof to the total mass of the biocompatible membrane supporting the 2 nd cyclic compound or a salt thereof is 0.5 or more and 50 or less by mass. When the ratio is 0.5 or more by mass, the 2 nd cyclic compound can be effectively permeated into the skin. When the 2 nd cyclic compound is supported on the biocompatible film at a ratio of 50 mass% or less, the biocompatible film is stably worn on the skin while maintaining high strength.

(4) Wearing liquid

When at least one of the 1 st cyclic compound and the 2 nd cyclic compound is a solid, the cosmetic or medical material may further include a dressing solution in order to allow the 1 st cyclic compound and the 2 nd cyclic compound to be uniformly supported on the biocompatible film and to be in close contact with the skin on which the biocompatible film is disposed. Biologically safe liquids may be used in the wearing fluid. For example, the wearing fluid includes 1 or more selected from aqueous solutions such as pure water, physiological saline, cosmetic water, and cosmetic liquid, cosmetic water containing an organic solvent, lotion, cosmetic liquid, cream, and the like. The wearing fluid desirably comprises water and a polyol. Examples of the polyhydric alcohol include glycerin and propylene glycol, and the wearing liquid may contain both glycerin and propylene glycol. Since the polyhydric alcohol is slightly hydrophobic as compared with water, the wearing liquid containing water and the polyhydric alcohol can dissolve both the 1 st ring compound and the 2 nd ring compound. Thus, the 1 st cyclic compound and the 2 nd cyclic compound can be uniformly arranged in the biocompatible membrane, and the 1 st cyclic compound and the 2 nd cyclic compound interact with each other to permeate the complex into the skin.

The concentration of the wearing liquid is desirably, for example, 5 mass% to 10 mass% of glycerin, 5 mass% to 15 mass% of propylene glycol, and the remainder of water. Since the liquid to be applied is less irritating to the skin and the like, the biocompatible film containing the liquid to be applied can be easily applied for a long period of time.

(5) Other ingredients

A component of a cosmetic or medical material other than the 1 st cyclic compound and the 2 nd cyclic compound may be contained. Examples of the ingredients of the cosmetic preparation include hyaluronic acid, ceramide, collagen, amino acids, elastin, various extracts, citric acid, lecithin, carbomer, xanthan gum, dextran, palmitic acid, lauric acid, vaseline, titanium oxide, iron oxide, phenoxyethanol, fullerene, astaxanthin, coenzyme, human oligopeptide, glycerin, diglycerin, sodium lactate, sorbitol, pyrrolidone carboxylic acid, polyglycerol fatty acid ester, polyglycerol, jojoba oil, trimethylglycine, mannitol, trehalose, glycosyl trehalose, pullulan (pullulan), erythritol, elastin, dipropylene glycol, butylene glycol, ethyl ethylhexanoate, sodium acrylate, disodium edetate, sucrose fatty acid ester, squalane, polyethylene glycol, polyoxyethylene hydrogenated castor oil, glyceryl stearate, ethanol, polyvinyl alcohol, hydroxyethyl cellulose, and the like, Ectoin, etc. Further, as the components of the medical material, isosorbide dinitrate, indomethacin, diflucortolone valerate, acyclovir, ketoconazole, ketoprofen, diclofenac sodium, dexamethasone propionate, felbinac, clobetasol propionate, loxoprofen, methyl salicylate, tacrolimus and the like can be given.

(forms of cosmetic or medical Material)

The cosmetic or medical material can be constituted in various forms.

(1) Supporting the 1 st and 2 nd cyclic compounds on a biocompatible membrane

The 1 st cyclic compound and the 2 nd cyclic compound may be previously supported on the biocompatible membrane. When the 1 st cyclic compound and the 2 nd cyclic compound are solid at ordinary temperature, the 1 st cyclic compound and the 2 nd cyclic compound may be supported on the biocompatible membrane in a solid state. For example, when the 2 nd cyclic compound is ascorbic acid, it is considered that the reduced form has a cosmetic effect such as suppression of melanin production, synthesis of hyaluronic acid, UV blocking, and the like. However, ascorbic acid is easily changed from a reducing type to an oxidizing type in an aqueous solution. Therefore, if reduced ascorbic acid as the 2 nd cyclic compound is supported on a biocompatible membrane in a solid state, it is less likely to be oxidized. The 1 st cyclic compound is similarly supported in a solid state. This enables the 1 st and 2 nd cyclic compounds to be stably retained for a long period of time.

The 1 st and 2 nd cyclic compounds may be supported in the biocompatible membrane, or may be supported on the surface of the biocompatible membrane. In order to inhibit the removal of the 1 st and 2 nd cyclic compounds possibly by friction or the like, it is desirable that the 1 st and 2 nd cyclic compounds are supported in the biocompatible film.

(2) Supporting one of the 1 st and 2 nd cyclic compounds on a biocompatible membrane

One of the 1 st cyclic compound and the 2 nd cyclic compound may be supported in advance on the biocompatible membrane. The other of the 1 st cyclic compound and the 2 nd cyclic compound may be configured in a biocompatible film by dissolving the other in a wearing solution and allowing the wearing solution to be contained in the biocompatible film, for example, when a cosmetic or medical material is used. For example, when the 1 st cyclic compound and the 2 nd cyclic compound have a strong interaction and thus have an adverse effect such as decomposition, they may not be supported on the biocompatible membrane for the purpose of separating and holding one.

(3) Post-arrangement of the 1 st and 2 nd cyclic compounds

The 1 st and 2 nd cyclic compounds can be separated from the biocompatible membrane and preserved. That is, the 1 st cyclic compound and the 2 nd cyclic compound may be disposed on the biocompatible membrane during use without being supported on the biocompatible membrane. In this case, for example, the 1 st cyclic compound and the 2 nd cyclic compound may be dissolved in a liquid to be applied, and the liquid to be applied with the 2 nd cyclic compound dissolved therein may be applied to the biocompatible film by dropping or the like. Alternatively, the 1 st wearing solution and the 2 nd wearing solution in which the 1 st cyclic compound and the 2 nd cyclic compound are dissolved, respectively, may be prepared and disposed by dropping the 1 st wearing solution and the 2 nd wearing solution onto a biocompatible film or the like at the time of use. In these forms, the 1 st cyclic compound and the 2 nd cyclic compound may be more disposed on the skin surface than in the case of being supported on a biocompatible film, and the amount of permeation into the skin may be increased.

(method of Using cosmetic Material or medical Material)

The cosmetic or medical material of the present disclosure is used by allowing a 1 st cyclic compound or a salt thereof and a 2 nd cyclic compound or a salt thereof to be retained in a biocompatible film and allowing the biocompatible film to contact the skin. When the biocompatible film is used in contact with the skin, the cosmetic or medical material of the present disclosure may be in any of the above forms (1) to (3) as long as the 1 st cyclic compound or a salt thereof and the 2 nd cyclic compound or a salt thereof are retained in the biocompatible film. The methods of using the cosmetic or medical material of the present disclosure are classified into the following 3 types according to the timing of preparing the wearing solution. In the case of using any of the above-described 3 usage patterns, the wearing liquid can be disposed at the following 3 timings.

(1) In the case of applying dropwise to the skin

The wearing solution is firstly dripped on the surface of the skin, and the biocompatible membrane is adhered to the skin in a mode of covering the dripped wearing solution.

(2) Case of performing dropwise addition to the biocompatible film

The wearing liquid is firstly contained in the biocompatible film, and the biocompatible film containing the wearing liquid is adhered to the skin.

(3) The dropping of the biocompatible film on the skin is carried out

The biocompatible membrane is first placed on the skin, and the wearing fluid is dropped from above the biocompatible membrane.

The biocompatible film can stably maintain the state where the skin is in contact with the wearing liquid, regardless of the use of the wearing liquid at any one of the times. Therefore, the 1 st cyclic compound and the 2 nd cyclic compound in the wearing liquid can be transdermally absorbed in the skin stably for a long time in an interacted state.

(Effect)

According to the cosmetic or medical material of the present disclosure, since the 1 st cyclic compound represented by formula (1) or a salt thereof and the 2 nd cyclic compound or a salt thereof as an active ingredient have a ring structure, the 1 st cyclic compound and the 2 nd cyclic compound are likely to interact with each other, and both the 1 st cyclic compound and the 2 nd cyclic compound are likely to permeate into the skin. The cyclic compound represented by formula (1) has a relatively large partition coefficient and is easily absorbed through the skin. Therefore, even if the 2 nd cyclic compound is water-soluble, that is, the 2 nd cyclic compound has a small partition coefficient and is a substance that is not easily absorbed through the skin, the 2 nd cyclic compound can be easily absorbed through the skin by forming a complex with the 1 st cyclic compound, and the 2 nd cyclic compound can efficiently permeate into the skin.

The cosmetic or medical material of the present disclosure is provided with a biocompatible film, and the biocompatible film can stably hold, for example, a 1 st cyclic compound or a salt thereof and a 2 nd cyclic compound or a salt thereof dissolved in a liquid. Since the biocompatible film is low in irritation, a cosmetic or medical material that can be attached to the skin at a time corresponding to the use can be realized.

(method for producing cosmetic or medical Material)

(1) 1 st and 2 nd cyclic compounds

As the 1 st cyclic compound and the 2 nd cyclic compound, commercially available products having purity, safety to a subject, and the like according to the application and need can be used.

(2) Wearing liquid

The wearing solution is a solution obtained by mixing pure water, physiological saline, commercially available aqueous solutions such as cosmetic water and beauty solution, cosmetic water containing an organic solvent, lotion, beauty solution, cream, etc., a solution containing a 1 st cyclic compound, a beauty/medical component, etc., and the above-mentioned polyhydric alcohol at the above-mentioned ratio.

(3) Biocompatible membranes

The biocompatible film containing regenerated cellulose as a main component can be produced, for example, by the following method.

First, a cellulose solution is prepared by dissolving cellulose in a solvent. The weight average molecular weight of the cellulose used is desirably 30,000 or more. Further, if cellulose having a weight average molecular weight of 150,000 or more is used, a biocompatible film having a thickness of 1300nm (1.3 μm) or less can be stably obtained.

As the cellulose, cellulose derived from plants such as pulp and cotton, or cellulose produced by organisms such as bacteria can be used as long as the cellulose has a predetermined weight average molecular weight. It is advantageous if the impurity concentration of the cellulose as the raw material is 10 wt% or less.

As the solvent, a solvent containing an ionic liquid can be used. By using a solvent containing at least an ionic liquid, cellulose can be dissolved in a relatively short time. The ionic liquid is a salt composed of an anion and a cation, and can exhibit a liquid state at a temperature of 150 ℃ or lower. As the ionic liquid for dissolving cellulose, an ionic liquid containing an amino acid or an alkyl phosphate ester can be used. By using such an ionic liquid as a solvent, cellulose can be dissolved while suppressing a decrease in molecular weight. In particular, since amino acids are components present in the living body, it can be said that an ionic liquid containing amino acids can produce a regenerated biocompatible film that is safer for the living body.

As the ionic liquid for dissolving cellulose, for example, an ionic liquid represented by the following general formula (s1) can be used. The ionic liquid represented by the general formula (s1) is an example in which the anion is an amino acid. In this example, the anion contains a terminal carboxyl group and a terminal amino group, as seen in the general formula (s 1). The cation of the ionic liquid represented by the general formula (s1) may be a quaternary ammonium cation.

In the general formula (s1), R₁～R₆Independently represents a hydrogen atom or a substituent. The substituents may be alkyl, hydroxyalkyl or phenyl, and the carbon chain may contain branches. The substituent may include amino, hydroxyl, carboxyl, and the like. n is an integer of 1 to 5 inclusive.

Alternatively, as the ionic liquid for dissolving cellulose, an ionic liquid represented by the following general formula (s2) may be used. In the following general formula (s2), R₁、R₂、R₃And R₄Independently represents a hydrogen atom or a carbon atom having 1 to 4 (C)₁-C₄) Alkyl group of (1).

The obtained cellulose solution was applied to an appropriate substrate to obtain a polymer gel sheet (also referred to as a liquid film) supported by the substrate. Then, the polymer gel sheet on the substrate is immersed in a liquid (hereinafter, sometimes referred to as "rinse liquid") that does not dissolve cellulose. The step may be a step of washing the polymer gel sheet by removing the solvent containing the ionic liquid from the polymer gel sheet.

The liquid (rinse solution) for impregnating the polymer gel sheet may be a solvent capable of dissolving at least in an ionic liquid. Examples of such liquids are water, methanol, ethanol, propanol, butanol, octanol, toluene, xylene, acetone, acetonitrile, dimethylacetamide, dimethylformamide, dimethylsulfoxide.

Then, the solvent and the like are removed from the polymer gel sheet. In other words, the polymer gel sheet is dried. As the drying method, various drying methods such as natural drying, vacuum drying, heat drying, freeze drying, supercritical drying, and the like can be applied. Vacuum heating may be performed. The drying conditions are not particularly limited, and any time and temperature sufficient for removing a part or all of the solvent, the rinse solution, and the like for dissolving the cellulose solution may be used. The biocompatible film is obtained by removing the solvent and the like from the polymer gel sheet.

In the case where at least one of the 1 st cyclic compound and the 2 nd cyclic compound is supported on the biocompatible membrane, for example, the biocompatible membrane obtained is immersed in a solution in which at least one of the 1 st cyclic compound and the 2 nd cyclic compound is dissolved before or/and after the solvent and the rinse solution are removed from the polymer gel sheet, and the biocompatible membrane is taken out of the solution and dried. Thus, a biocompatible membrane supporting at least one of the 1 st cyclic compound and the 2 nd cyclic compound is obtained.

Examples of the solvent for dissolving the 1 st cyclic compound and the 2 nd cyclic compound include water, ethanol, propanol, butanol, acetone, glycerol, propylene glycol, 1, 3-butanediol, 1, 4-butanediol, diglycerol, polyethylene glycol, and polydimethylsiloxane (dimethicone). In addition, a plurality of these solutions may be used. The sheet may be impregnated with a solution containing a component for beauty/medical use or the like and carried, or the component for beauty/medical use or the like may be carried by spraying, vapor deposition or the like.

The active ingredient other than the 1 st cyclic compound and the 2 nd cyclic compound may be supported on the biocompatible membrane in the same manner.

(examples)

Examples of the cosmetic or medical material of the present disclosure are described below.

In the examples, the compounds shown in tables 1 to 3 below were used as the 1 st cyclic compound and the 2 nd cyclic compound. Further, as comparative examples, nicotinamide and hydroxyisocaproic acid (leuconic acid) used in place of the 1 st cyclic compound are shown in table 2. In the following examples, the 2 nd cyclic compound is sometimes referred to as a cosmetic agent.

[ Table 1]

TABLE 1

[ Table 2]

TABLE 2

[ Table 3]

TABLE 3

(1) Example 1

Example 1 is composed of example 1A to example 1I. In example 1, a biocompatible membrane in which ascorbic acid or sodium ascorbate as a 2 nd cyclic compound, nicotinic acid or sodium nicotinate or gallic acid or sodium ferulate or pyridoxal hydrochloride or menthol as a 1 st cyclic compound was supported in a membrane was used.

< example 1A >)

(preparation of biocompatible film)

Cellulose having a purity of 90% or more and derived from bleached pulp using wood as a raw material is dissolved in an ionic liquid to prepare a cellulose solution. As the ionic liquid, R in the formula (s2) is used₁Is methyl, R₂～R₄An ionic liquid which is ethyl. A polymer gel sheet is formed by applying a cellulose solution to a substrate. At this time, the thickness of the biocompatible film was adjusted to 900nmThe coating thickness is integrated. The washing of the substrate and the polymer gel sheet is performed.

Further, the washed polymer gel sheet was immersed in a solution in which sodium ascorbate and sodium nicotinate were dissolved in water, and dried, thereby obtaining a biocompatible membrane supporting the 1 st ring compound and the 2 nd ring compound of example 1A, in which 2.7% of sodium ascorbate and 0.2% of sodium nicotinate were supported by mass ratio with respect to the membrane. The film had a shape of approximately 5cm square and a transparent appearance.

(method for determining the amount of the 2 nd Ring-type Compound and the 1 st Ring-type Compound in the film)

The mass ratio of sodium ascorbate and sodium nicotinate in the film with respect to the film was obtained by the following method. In advance, sodium nicotinate was dissolved in ultrapure water, and the concentration and the absorbance at 266nm and 220nm measured by an absorptiometer UV-1600 (Shimadzu corporation) were plotted as standard curves to obtain slopes a₂₆₆、a₂₂₀. In the same manner as above, sodium ascorbate was dissolved in ultrapure water, and a standard curve was prepared with respect to the concentration thereof and the absorbance at 266nm, and the slope b was obtained₂₆₆. Immersing the membrane in ultrapure water, and extracting the components in the membrane for 1 hour by ultrasonic wave to obtain an absorbance I at 220nm of the solution₂₂₀The concentration C of nicotinic acid in the extracted solution was determined using the calibration curve_N. Further, the amount of the extracted solution L was multiplied by the mass of the membrane W to obtain the mass ratio D of sodium ascorbate in the membrane_N. Namely, the following equation is given.

[ number 1]

[ number 2]

On the other hand, sodium ascorbate cannot be directly calculated because sodium ascorbate covers a part of the spectrum of sodium ascorbate and sodium nicotinateAnd (4) concentration. Thus, first, the absorbance I of the extracted liquid was obtained₂₆₆. Next, the sodium nicotinate concentration C obtained from the reaction_NThe absorbance I at 266nm obtained from sodium nicotinate was calculated_N266. Using these values and b₂₆₆The ascorbic acid concentration C is obtained by using the formulas (III) and (IV)_AAnd the mass ratio D of sodium ascorbate in the film_N。

[ number 3]

[ number 4]

(verification of cosmetic Effect of cultured skin on biocompatible film retaining Compound 2 nd Ring)

MEL-300A (house application textile Co., Ltd., MEL below) was used as a three-dimensional cultured epidermal model containing melanocytes. In the culture test, CO was used₂Incubator (37 degree, 5% CO)₂) The culture was maintained and cultured using EPI-100LLMM long-term maintenance medium (EPI, described below, by Bin Pazuo Co., Ltd.). After MEL was transferred to the plate, preculture was performed with 2ml of EPI. Next, MEL was transferred to a plate to which 5ml of EPI was added. The membrane of example 1A was placed on the keratinous side of MEL, and the membrane surface was wetted with phosphoric acid buffered saline (PBS). EPI was replaced 1 time every 2 days after the membrane was set up and after this, the biocompatible membrane and PBS were replaced 1 time every 4 days.

The cultured skin permeation concentration P of sodium ascorbate 1 day after the membrane was set was determined by the same method as in formulas (I) to (III) of (method for determining the amount of 2. sup. nd ring compound and 1. sup. st ring compound in the membrane) except that EPI was used instead of ultrapure water_A. Cultured skin permeation concentration P of the obtained sodium ascorbate_AAnd amount of solution V of EPI_EPIThe cultured skin permeation amount M of sodium ascorbate after 1 day was determined using the formula (V)_A。

[ number 5]

M_A＝P_A×V_EPIFormula (V)

After further culturing for 2 weeks, the cell survival rate of MEL was determined by alamar blue method. A solution of 0.20g of Amar blue (コスモバイオ Co.) added to 1.8g of EPI was added dropwise to the plate to prepare MEL. After culturing for 2 hours, the fluorescence intensity of the culture supernatant (excitation wavelength: 544nm, measurement wavelength: 590nm) was measured by a spectrofluorometer FP-8500(JASCO Co.). The cell survival rate was calculated as a ratio to the fluorescence intensity when the membrane of comparative example 1A described later was added.

After washing MEL with PBS, cultured skin sites were cut out of MEL and transferred to glass bottles. Further, the mixture was subjected to displacement washing in ethyl ether in a solution of ethanol and ethyl ether at an equal mass ratio for at least half a day. The melanin pigment in the cultured skin was dissolved by immersing the washed cultured skin portion in a 1M aqueous solution of sodium hydroxide. The absorbance at 405nm was measured by an absorptiometer UV-1600 (Shimadzu corporation), and the melanin content in the cultured skin was calculated from a calibration curve obtained in advance from the dissolution concentration and absorbance of the synthesized melanin (シグマアルドリッチジャパン Co.).

< example 1B >)

A film was obtained in the same manner as in example 1A except that a cosmetic component solution in which sodium ascorbate and nicotinic acid were dissolved was used in the preparation of the biocompatible film in example 1A and 2.6% sodium ascorbate and 0.2% nicotinic acid were supported on the film at a mass ratio. The cosmetic effect verification was also evaluated by the same method as in example 1A.

< example 1C >)

A film was obtained in the same manner as in example 1A except that a cosmetic component solution in which ascorbic acid and sodium nicotinate were dissolved was used in the production of the biocompatible film in example 1A, and 2.6% ascorbic acid and 0.2% sodium nicotinate were carried as mass ratios to the film. The cosmetic effect verification was also evaluated by the same method as in example 1A.

< example 1D >)

A film was obtained in the same manner as in example 1A except that a cosmetic component solution in which ascorbic acid and nicotinic acid were dissolved was used in the preparation of the biocompatible film in example 1A, and a film in which 2.7% ascorbic acid and 0.2% nicotinic acid were supported by the film as mass ratios thereof was obtained. The cosmetic effect verification was also evaluated by the same method as in example 1A.

< example 1E >)

A film was obtained in the same manner as in example 1A, except that a cosmetic component solution in which sodium ascorbate and sodium vanillite were dissolved was used in the preparation of the biocompatible film in example 1A, and 2.7% sodium ascorbate and 0.2% sodium vanillic acid were supported in a mass ratio with respect to the film. The cosmetic effect verification was also evaluated by the same method as in example 1A.

< example 1F >)

A membrane was obtained in the same manner as in example 1A, except that a cosmetic component solution obtained by dissolving sodium ascorbate and gallic acid was used and that 2.7% of sodium ascorbate and 0.2% of gallic acid were supported on the membrane at a mass ratio based on the membrane in the preparation of the biocompatible membrane in example 1A. The cosmetic effect verification was also evaluated by the same method as in example 1A.

< example 1G >)

A film was obtained in the same manner as in example 1A except that a cosmetic component solution in which sodium ascorbate and sodium ferulate were dissolved was used and that 2.7% sodium ascorbate and 0.2% sodium ferulate were supported by the film in a mass ratio based on the film in the preparation of the biocompatible film in example 1A. The cosmetic effect verification was also evaluated by the same method as in example 1A.

< example 1H >)

A film was obtained in the same manner as in example 1A except that a cosmetic component solution in which sodium ascorbate and pyridoxal hydrochloride were dissolved was used in the preparation of the biocompatible film in example 1A, and 2.7% of sodium ascorbate and 0.2% of pyridoxal hydrochloride were supported by the film in a mass ratio. The cosmetic effect verification was also evaluated by the same method as in example 1A.

< example 1I >)

A film was obtained in the same manner as in example 1A except that in the preparation of the biocompatible film in example 1A, a cosmetic composition solution in which sodium ascorbate and menthol were dissolved was used for the washed polymer gel sheet, and 2.7% sodium ascorbate and 0.2% menthol were supported as mass ratios to the film. The amount of menthol in the film was determined by subtracting the amount of sodium ascorbate obtained from the reaction amount using acetic anhydride from the amount of sodium ascorbate in the film obtained by the same method as in example 1A (method for determining the amount of the 2 nd ring compound and the 1 st ring compound in the film). The cosmetic effect verification was also evaluated by the same method as in example 1A.

< comparative example 1 >

Comparative example 1 was composed of comparative example 1A to comparative example 1N. In comparative example 1, a biocompatible membrane carrying no carrier or a biocompatible membrane carrying only the 2 nd cyclic compound or the 1 st cyclic compound was used.

< comparative example 1A >)

A biocompatible film was obtained in the same manner as in example 1A, except that the biocompatible film of example 1A was not immersed in a cosmetic component solution. The cosmetic effect verification was also evaluated by the same method as in example 1A.

< comparative example 1B >)

A film was obtained in the same manner as in example 1A, except that a cosmetic component solution in which sodium ascorbate was dissolved was used and 2.7% sodium ascorbate was supported on the film in a mass ratio to the film in the preparation of the biocompatible film in example 1A. The cosmetic effect verification was also evaluated by the same method as in example 1A.

< comparative example 1C >

A film was obtained in the same manner as in example 1A, except that a cosmetic component solution in which ascorbic acid was dissolved was used in the preparation of the biocompatible film in example 1A, and 2.6% ascorbic acid was supported by the solution in terms of mass ratio to the film. The cosmetic effect verification was also evaluated by the same method as in example 1A.

< comparative example 1D >

A film was obtained in the same manner as in example 1A, except that a cosmetic ingredient solution in which sodium nicotinate was dissolved was used in the preparation of the biocompatible film in example 1A, and 0.2% of sodium nicotinate was supported by the solution in terms of mass ratio with respect to the film. The cosmetic effect verification was also evaluated by the same method as in example 1A.

< comparative example 1E >

A film was obtained in the same manner as in example 1A, except that a cosmetic component solution obtained by dissolving nicotinic acid was used in the preparation of the biocompatible film in example 1A and that 0.2% by mass of nicotinic acid was supported on the film. The cosmetic effect verification was also evaluated by the same method as in example 1A.

< comparative example 1F >

A film was obtained in the same manner as in example 1A, except that a cosmetic ingredient solution in which sodium vanillite was dissolved was used in the preparation of the biocompatible film in example 1A, and 0.2% of sodium vanillite was supported as a mass ratio with respect to the film. The cosmetic effect verification was also evaluated by the same method as in example 1A.

< comparative example 1G >)

A film was obtained in the same manner as in example 1A, except that a cosmetic composition solution obtained by dissolving gallic acid was used and that 0.2% of gallic acid was supported on the film as a mass ratio thereof in the preparation of the biocompatible film in example 1A. The cosmetic effect verification was also evaluated by the same method as in example 1A.

< comparative example 1H >

A film was obtained in the same manner as in example 1A, except that a cosmetic component solution in which sodium ferulate was dissolved was used in the preparation of the biocompatible film in example 1A, and 0.2% sodium ferulate was supported by the solution in terms of mass ratio to the film. The cosmetic effect verification was also evaluated by the same method as in example 1A.

< comparative example 1I >

A film was obtained in the same manner as in example 1A, except that a cosmetic ingredient solution in which pyridoxal hydrochloride was dissolved was used in the preparation of the biocompatible film in example 1A, and that 0.2% of pyridoxal hydrochloride was supported by the cosmetic ingredient solution in a mass ratio to the film. The cosmetic effect verification was also evaluated by the same method as in example 1A.

< comparative example 1J >

A film was obtained in the same manner as in example 1A, except that a cosmetic component solution in which menthol was dissolved was used in the preparation of the biocompatible film in example 1A, and 0.2% of menthol was supported on the film in terms of the mass ratio. The cosmetic effect verification was also evaluated by the same method as in example 1A.

< comparative example 1K >

A film was obtained in the same manner as in example 1A except that a cosmetic component solution in which sodium ascorbate and nicotinamide were dissolved was used in the preparation of the biocompatible film in example 1A, and 2.7% of sodium ascorbate and 0.2% of nicotinamide were supported by the cosmetic component solution in a mass ratio to the film. The cosmetic effect verification was also evaluated by the same method as in example 1A.

< comparative example 1L >)

A film was obtained in the same manner as in example 1A except that a cosmetic component solution in which niacinamide was dissolved was used in the preparation of the biocompatible film in example 1A and 0.2% of niacinamide was supported as a mass ratio to the film. The cosmetic effect verification was also evaluated by the same method as in example 1A.

< comparative example 1M >

A film was obtained in the same manner as in example 1A except that a cosmetic component solution obtained by dissolving sodium ascorbate and hydroxyisocaproic acid was used in the preparation of the biocompatible film in example 1A and 2.7% sodium ascorbate and 0.2% hydroxyisocaproic acid were supported by the film in terms of mass ratio. The cosmetic effect verification was also evaluated by the same method as in example 1A.

< comparative example 1N >

A film was obtained in the same manner as in example 1A, except that a cosmetic component solution obtained by dissolving hydroxyisocaproic acid was used in the preparation of the biocompatible film in example 1A and that 0.2% hydroxyisocaproic acid was supported on the film in a mass ratio. The cosmetic effect verification was also evaluated by the same method as in example 1A.

Examination of example 1

Table 4 shows the cultured skin permeation amount of ascorbic acid or sodium ascorbate [ mu mol/day ] after 1 day and the cultured skin production amount of melanin [ mu g/well ] produced in the cultured skin in the two-week culture period in examples 1A to 1I and comparative examples 1A to 1N. In addition, it was confirmed that the cell survival rate was 90% or more in both examples and comparative examples.

[ Table 4]

TABLE 4

From Table 4, when example 1A was compared with comparative examples 1A, 1B and 1D, the permeation amount of the 2 nd cyclic compound (cosmetic agent) was dramatically increased by supporting 2.7% sodium ascorbate and 0.2% sodium nicotinate, and the amount of melanin produced was decreased.

When example 1B is compared with comparative examples 1A, 1B and 1E, the 2 nd cyclic compound permeability is dramatically increased by supporting 2.6% sodium ascorbate and 0.2% nicotinic acid, and the amount of melanin produced is decreased.

When example 1C was compared with comparative examples 1A, 1C and 1D, the 2 nd cyclic compound permeability was dramatically increased and the amount of melanin produced was reduced by supporting 2.6% ascorbic acid and 0.2% sodium nicotinate.

When example 1D was compared with comparative examples 1A, 1C and 1E, the permeation amount of the 2 nd cyclic compound was dramatically increased by supporting 2.7% ascorbic acid and 0.2% nicotinic acid, and the amount of melanin produced was decreased.

When example 1E was compared with comparative examples 1A, 1B and 1F, the permeation amount of the 2 nd cyclic compound was dramatically increased by supporting 2.7% sodium ascorbate and 0.2% sodium oxalate, and the amount of melanin produced was decreased.

When example 1F was compared with comparative examples 1A, 1B and 1G, the 2 nd cyclic compound permeability was dramatically increased by supporting 2.7% sodium ascorbate and 0.2% gallic acid, and the amount of melanin produced was decreased.

When example 1G was compared with comparative examples 1A, 1B and 1H, the 2 nd cyclic compound permeability was dramatically increased by supporting 2.7% sodium ascorbate and 0.2% sodium ferulate, and the amount of melanin produced was decreased.

When example 1H is compared with comparative examples 1A, 1B and 1I, the permeation amount of the 2 nd cyclic compound is dramatically increased by supporting 2.7% sodium ascorbate and 0.2% pyridoxal hydrochloride, and the amount of melanin produced is decreased.

When example 1I is compared with comparative examples 1A, 1B and 1J, the 2 nd cyclic compound permeability is dramatically increased and the amount of melanin produced is decreased by supporting 2.7% sodium ascorbate and 0.2% menthol.

When comparative example 1K was compared with comparative examples 1A, 1B and 1L, it was found that the permeation amount of the 2 nd cyclic compound was not increased and the amount of melanin production was not decreased by the loading of 2.7% sodium ascorbate and 0.2% nicotinamide.

When comparative example 1M was compared with comparative examples 1A, 1B and 1N, it was found that the permeation amount of the 2 nd cyclic compound was not increased and the amount of melanin production was not decreased by the supporting of 2.7% sodium ascorbate and 0.2% hydroxyisocaproic acid.

From the above, the cultured skin permeation amount of ascorbic acid and sodium ascorbate of the 1 st cyclic compound and the 2 nd cyclic compound (cosmetic) is dramatically increased by using sodium nicotinate, nicotinic acid, sodium oxalate, gallic acid, sodium ferulate, pyridoxal hydrochloride, and menthol as the 1 st cyclic compound, and the cultured skin production amount can be suppressed.

< example 2 >

Example 2 consisted of examples 2A-2G. The amount of reduced ascorbic acid in the biocompatible film produced in example 1 was examined over a long period of time.

< example 2A >)

In the preparation of the biocompatible film of example 1A, a biocompatible film was obtained in the same manner as in example 1A. The biocompatible membrane stored for one week or four at the initial stage and 20 ℃ was immersed in 2g of ultrapure water and subjected to ultrasonic cleaning for 1 hour. The amount of reduced ascorbic acid in this solution was determined by an ascorbic acid quantification kit (BioVision), and the ratio of reduced ascorbic acid was determined by normalizing the amount of sodium ascorbate contained in the initial membrane.

< example 2B >)

In the preparation of the biocompatible film of example 1A, a biocompatible film was obtained in the same manner as in example 1B. The same procedure as in example 2A was followed to determine the ratio of reduced ascorbic acid in the initial stage after storage for one week or four weeks.

< example 2C >)

In the preparation of the biocompatible film of example 1A, a biocompatible film was obtained in the same manner as in example 1E. The same procedure as in example 2A was followed to determine the ratio of reduced ascorbic acid in the initial stage after storage for one week or four weeks.

< example 2D >)

In the preparation of the biocompatible film of example 1A, a biocompatible film was obtained in the same manner as in example 1F. The same procedure as in example 2A was followed to determine the ratio of reduced ascorbic acid in the initial stage after storage for one week or four weeks.

< example 2E >)

In the preparation of the biocompatible film of example 1A, a biocompatible film was obtained in the same manner as in example 1G. The same procedure as in example 2A was followed to determine the ratio of reduced ascorbic acid in the initial stage after storage for one week or four weeks.

< example 2F >)

In the preparation of the biocompatible membrane in example 1A, a biocompatible membrane was obtained in the same manner as in example 1H. The same procedure as in example 2A was followed to determine the ratio of reduced ascorbic acid in the initial stage after storage for one week or four weeks.

< example 2G >)

In the preparation of the biocompatible film of example 1A, a biocompatible film was obtained in the same manner as in example 1I. The same procedure as in example 2A was followed to determine the ratio of reduced ascorbic acid in the initial stage after storage for one week or four weeks.

< comparative example 2 >

Comparative example 2 consisted of comparative examples 2A-2G. The amount of reduced ascorbic acid was determined from an aqueous solution obtained by dissolving sodium ascorbate and a 1 st cyclic compound.

< comparative example 2A >)

PBS was prepared by dissolving 3.0% and 0.2% of sodium ascorbate and sodium nicotinate, respectively, in the mass ratio of the solutions. After the solution was shaken to sufficiently contain air in the aqueous solution, the solution was stored at 20 ℃ for one week or four weeks. The same procedure as in example 1A was carried out to determine the ratio of reduced ascorbic acid in the initial stage after storage for one week or four weeks.

< comparative example 2B >)

An aqueous solution was prepared in the same manner as in comparative example 2A, except that 3.0% and 0.2% by mass of PBS was dissolved in each of sodium ascorbate and nicotinic acid. The same procedure as in example 1A was carried out to determine the ratio of reduced ascorbic acid in the initial stage after storage for one week or four weeks.

< comparative example 2C >

An aqueous solution was prepared in the same manner as in comparative example 2A, except that 3.0% and 0.2% by mass of each of sodium ascorbate and sodium phenoxide was dissolved in the solution. The same procedure as in example 1A was carried out to determine the ratio of reduced ascorbic acid in the initial stage after storage for one week or four weeks.

< comparative example 2D >

An aqueous solution was prepared in the same manner as in comparative example 2A, except that 3.0% and 0.2% by mass of PBS was dissolved in each of sodium ascorbate and gallic acid. The same procedure as in example 1A was carried out to determine the ratio of reduced ascorbic acid in the initial stage after storage for one week or four weeks.

< comparative example 2E >

An aqueous solution was prepared in the same manner as in comparative example 2A, except that 3.0% and 0.2% by mass of PBS was dissolved in each of sodium ascorbate and sodium ferulate. The same procedure as in example 1A was carried out to determine the ratio of reduced ascorbic acid in the initial stage after storage for one week or four weeks.

< comparative example 2F >

An aqueous solution was prepared in the same manner as in comparative example 2A, except that 3.0% and 0.2% by mass of PBS was dissolved in each of sodium ascorbate and pyridoxal hydrochloride in the solution. The same procedure as in example 1A was carried out to determine the ratio of reduced ascorbic acid in the initial stage after storage for one week or four weeks.

< comparative example 2G >

An aqueous solution was prepared in the same manner as in comparative example 2A, except that 3.0% and 0.2% by mass of PBS was dissolved in each of sodium ascorbate and menthol. The same procedure as in example 1A was carried out to determine the ratio of reduced ascorbic acid in the initial stage after storage for one week or four weeks.

Examination of example 2

The ratios of the amounts of reduced ascorbic acid to the initial amounts after one week and four weeks with respect to examples 2A to 2F and comparative examples 2A to 2F are shown in table 5.

[ Table 5]

TABLE 5

According to Table 5, reduced ascorbic acid was stably retained at least all around by dry-supporting ascorbic acid in the sheet.

< example 3 >

Example 3 is composed of examples 3A to 3F. In example 3, a biocompatible membrane in which sodium ascorbate as a 2 nd cyclic compound and sodium nicotinate as a 1 st cyclic compound were supported on a membrane was used.

< example 3A >)

A film was obtained in the same manner as in example 1A except that a cosmetic component solution in which sodium ascorbate and sodium nicotinate were dissolved was used and that 0.5% sodium ascorbate and 0.1% sodium nicotinate were supported on the film at a mass ratio with respect to the film in the production of the biocompatible film in example 1A. The cosmetic effect verification was also evaluated by the same method as in example 1A.

< example 3B >)

A film was obtained in the same manner as in example 1A, except that in the preparation of the biocompatible film of example 1A, the washed polymer gel sheet was immersed in a cosmetic composition solution in which sodium ascorbate and sodium nicotinate were dissolved, and 0.5% sodium ascorbate and 0.2% sodium nicotinate were supported as mass ratios to the film. The cosmetic effect verification was also evaluated by the same method as in example 1A.

< example 3C >)

A film was obtained in the same manner as in example 1A except that a cosmetic component solution in which sodium ascorbate and sodium nicotinate were dissolved was used and 0.8% sodium ascorbate and 0.1% sodium nicotinate were supported on the film in a mass ratio based on the film in the production of the biocompatible film in example 1A. The cosmetic effect verification was also evaluated by the same method as in example 1A.

< example 3D >

A film was obtained in the same manner as in example 1A except that a cosmetic component solution in which sodium ascorbate and sodium nicotinate were dissolved was used and 0.8% sodium ascorbate and 0.2% sodium nicotinate were supported on the film in a mass ratio based on the film in the production of the biocompatible film in example 1A. The cosmetic effect verification was also evaluated by the same method as in example 1A.

< example 3E >)

A film was obtained in the same manner as in example 1A except that a cosmetic component solution in which sodium ascorbate and sodium nicotinate were dissolved was used and 0.8% sodium ascorbate and 4.6% sodium nicotinate were supported by the film at a mass ratio to the film in the production of the biocompatible film in example 1A. The cosmetic effect verification was also evaluated by the same method as in example 1A.

< example 3F >)

A film was obtained in the same manner as in example 1A except that a cosmetic component solution in which sodium ascorbate and sodium nicotinate were dissolved was used and that 4.6% of sodium ascorbate and 0.2% of sodium nicotinate were supported by the film at a mass ratio with respect to the film in the production of the biocompatible film in example 1A. The cosmetic effect verification was also evaluated by the same method as in example 1A.

< comparative example 3 >

Comparative example 3 is composed of comparative example 3A to comparative example 3D. In comparative example 3, a biocompatible membrane in which only sodium ascorbate or sodium nicotinate was supported was used.

< comparative example 3A >)

A film was obtained in the same manner as in example 1A, except that a cosmetic ingredient solution in which sodium nicotinate was dissolved was used in the preparation of the biocompatible film in example 1A, and 0.1% of sodium nicotinate was supported by the solution in terms of mass ratio with respect to the film. The cosmetic effect verification was also evaluated by the same method as in example 1A.

< comparative example 3B >)

A film was obtained in the same manner as in example 1A, except that a cosmetic ingredient solution in which sodium nicotinate was dissolved was used in the preparation of the biocompatible film in example 1A, and 4.6% of sodium nicotinate was supported by the solution in terms of mass ratio with respect to the film. The cosmetic effect verification was also evaluated by the same method as in example 1A.

< comparative example 3C >

A film was obtained in the same manner as in example 1A, except that a cosmetic component solution in which sodium ascorbate was dissolved was used and 0.5% sodium ascorbate was supported on the film in a mass ratio to the film in the preparation of the biocompatible film in example 1A. The cosmetic effect verification was also evaluated by the same method as in example 1A.

< comparative example 3D >

A film was obtained in the same manner as in example 1A, except that a cosmetic component solution in which sodium ascorbate was dissolved was used and 0.8% sodium ascorbate was supported on the film in a mass ratio to the film in the preparation of the biocompatible film in example 1A. The cosmetic effect verification was also evaluated by the same method as in example 1A.

Examination of example 3

Table 6 shows the cultured skin permeation amount [ μmol/day ] of sodium ascorbate after 1 day in examples 1A, 3A to 3F and comparative examples 1A, 1B, 1D and 3A to 3D, and the melanin production amount [ μ g/well ] generated in the cultured skin in the two-week culture period. In addition, it was confirmed that the cell survival rate was 90% or more in both examples and comparative examples.

[ Table 6]

TABLE 6

According to Table 6, when PBS and a biocompatible film carrying 0.5% or more of sodium ascorbate and 0.1% or more of sodium nicotinate were used, the permeation amount of the 2 nd cyclic compound increased and the amount of melanin production significantly decreased.

< example 4 >

Based on example 1A, in the verification of the cosmetic effect, glycerin of 10% by mass, propylene glycol of 5% by mass, and a PBS solution of 85% by mass were used instead of PBS, and the amount of melanin production was examined.

< example 4A >)

In the preparation of the biocompatible film of example 1A, a biocompatible film was obtained in the same manner as in example 1A. A cosmetic effect test was performed as in example 1A, except that PBS containing 10% by mass of glycerin and 5% by mass of propylene glycol was used instead of PBS alone for the cosmetic effect test.

Examination of example 4

Table 7 shows the cultured skin permeation amount of sodium ascorbate [ mu mol/day ] after 1 day in examples 1A, 4A and comparative example 1A, and the melanin production amount [ mu g/well ] generated in the cultured skin in the two-week culture period. In addition, the cell survival rate was confirmed to be 90% or more in both examples and comparative examples.

[ Table 7]

TABLE 7

From table 7, if example 4A is compared with example 1A and comparative example 1A, it is understood that the amount of melanin production can be suppressed to a level higher than PBS by using a PBS solution containing 10% glycerol and 5% propylene glycol, compared with PBS alone.

< example 5 >

Example 5 was composed of examples 5A to 5F. In example 5, a biocompatible film in which only sodium ascorbate was supported on the film was prepared, and PBS to which sodium nicotinate was added was used instead of PBS for cosmetic effect verification.

< example 5A >)

In the preparation of the biocompatible film of example 1A, a biocompatible film was obtained in the same manner as in comparative example 3C. The cosmetic effect was evaluated by the same method as in example 1A except that PBS to which 0.10% by mass of sodium nicotinate was added to the biocompatible film was used instead of PBS.

< example 5B >)

In the preparation of the biocompatible film of example 1A, a biocompatible film was obtained in the same manner as in comparative example 3C. The cosmetic effect was evaluated by the same method as in example 1A except that PBS to which 0.20% by mass of sodium nicotinate was added to the biocompatible film was used instead of PBS.

< example 5C >

In the preparation of the biocompatible film of example 1A, a biocompatible film was obtained in the same manner as in comparative example 3D. The cosmetic effect was evaluated by the same method as in example 1A except that PBS to which 0.10% by mass of sodium nicotinate was added to the biocompatible film was used instead of PBS.

< example 5D >

In the preparation of the biocompatible film of example 1A, a biocompatible film was obtained in the same manner as in comparative example 3D. The cosmetic effect was evaluated by the same method as in example 1A except that PBS to which 0.20% by mass of sodium nicotinate was added to the biocompatible film was used instead of PBS.

< example 5E >)

In the preparation of the biocompatible film of example 1A, a biocompatible film was obtained in the same manner as in comparative example 3D. The cosmetic effect was evaluated by the same method as in example 1A except that PBS to which sodium nicotinate was added in a mass ratio of 5.0% to the biocompatible film was used instead of PBS.

< example 5F >

In the preparation of the biocompatible film of example 1A, a biocompatible film was obtained in the same manner as in comparative example 1B. The cosmetic effect was evaluated by the same method as in example 1A except that PBS to which 0.20% by mass of sodium nicotinate was added to the biocompatible film was used instead of PBS.

< comparative example 4 >

Comparative example 4 is composed of comparative examples 4A to 4C. In comparative example 4, sodium nicotinate-added PBS was used instead of PBS.

< comparative example 4A >)

In the preparation of the biocompatible film of example 1A, a biocompatible film was obtained in the same manner as in comparative example 1A. The cosmetic effect was evaluated by the same method as in example 1A except that PBS to which 0.10% by mass of sodium nicotinate was added to the biocompatible film was used instead of PBS.

< comparative example 4B >)

In the preparation of the biocompatible film of example 1A, a biocompatible film was obtained in the same manner as in comparative example 1A. The cosmetic effect was evaluated by the same method as in example 1A except that PBS to which 0.20% by mass of sodium nicotinate was added to the biocompatible film was used instead of PBS.

< comparative example 4C >

In the preparation of the biocompatible film of example 1A, a biocompatible film was obtained in the same manner as in comparative example 1A. The cosmetic effect was evaluated by the same method as in example 1A except that PBS to which sodium nicotinate was added in a mass ratio of 5.0% to the biocompatible film was used instead of PBS.

Examination of example 5

Table 8 shows the cultured skin permeation amount [ mu mol/day ] of sodium ascorbate after 1 day in examples 5A to 5F and comparative examples 1A, 1B, 3C, 3D, and 4A to 4C, and the melanin production amount [ mu g/well ] generated in the cultured skin in the two-week culture period. In addition, the cell survival rate was confirmed to be 90% or more in both examples and comparative examples.

[ Table 8]

TABLE 8

According to table 8, when the film carrying 0.5% or more of sodium ascorbate was used and PBS containing 0.10% or more of sodium nicotinate was used, the amount of penetration of the 2 nd cyclic compound (cosmetic agent) was increased, and the amount of melanin production was significantly reduced.

< example 6 >

Example 6 is composed of examples 6A to 6C. In example 6, a biocompatible film in which only sodium ascorbate was supported on the film was prepared, and PBS to which nicotinic acid was added was used instead of PBS for the verification of the cosmetic effect.

< example 6A >

In the preparation of the biocompatible film of example 1A, a biocompatible film was obtained in the same manner as in comparative example 3D. The cosmetic effect was evaluated in the same manner as in example 1A except that PBS to which 0.20% by mass of nicotinic acid was added to the biocompatible film was used instead of PBS.

< example 6B >)

In the preparation of the biocompatible film of example 1A, a biocompatible film was obtained in the same manner as in comparative example 1B. The cosmetic effect was evaluated in the same manner as in example 1A except that PBS to which 0.20% by mass of nicotinic acid was added to the biocompatible film was used instead of PBS.

< example 6C >

In the preparation of the biocompatible film of example 1A, a biocompatible film was obtained in the same manner as in comparative example 1B. The cosmetic effect was evaluated in the same manner as in example 1A except that PBS to which nicotinic acid was added in a mass ratio of 2.0% to the biocompatible film was used instead of PBS.

< comparative example 5 >

Comparative example 5 includes comparative example 5A to comparative example 5B. In comparative example 5, in the verification of the biocompatible film and the cosmetic effect, PBS to which nicotinic acid was added was used instead of PBS.

< comparative example 5A >)

In the preparation of the biocompatible film of example 1A, a biocompatible film was obtained in the same manner as in comparative example 1A. The cosmetic effect was evaluated in the same manner as in example 1A except that PBS to which 0.20% by mass of nicotinic acid was added to the biocompatible film was used instead of PBS.

< comparative example 5B >)

In the preparation of the biocompatible film of example 1A, a biocompatible film was obtained in the same manner as in comparative example 1A. The cosmetic effect was evaluated in the same manner as in example 1A except that PBS to which nicotinic acid was added in a mass ratio of 2.0% to the biocompatible film was used instead of PBS.

Examination of example 6

Table 9 shows the cultured skin permeation amount [ μmol/day ] of sodium ascorbate after 1 day in examples 6A to 6C and comparative examples 1A, 1B, 3D, 5A, and 5B, and the melanin production amount [ μ g/well ] generated in the cultured skin in the two-week culture period. In addition, it was confirmed that the cell survival rate was 90% or more in both examples and comparative examples.

[ Table 9]

TABLE 9

According to table 9, when a film carrying 0.8% or more of sodium ascorbate and PBS containing 0.20% or more of nicotinic acid were used, the permeation amount of the 2 nd cyclic compound (cosmetic agent) was increased, and the amount of melanin production was significantly decreased.

< example 7 >

Example 7 consisted of example 7A. In example 7, a biocompatible film in which only sodium ascorbate was supported on the film was prepared, and PBS to which gallic acid was added was used instead of PBS for the verification of the cosmetic effect.

< example 7A >

In the preparation of the biocompatible film of example 1A, a biocompatible film was obtained in the same manner as in comparative example 1B. The cosmetic effect was evaluated by the same method as in example 1A except that PBS to which gallic acid was added in a mass ratio of 0.20% to the biocompatible film was used instead of PBS.

< comparative example 6 >

Comparative example 6 was composed of comparative example 6A. In comparative example 6, a biocompatible film was prepared, and PBS to which gallic acid was added was used instead of PBS for cosmetic effect verification.

< comparative example 6A >)

In the preparation of the biocompatible film of example 1A, a biocompatible film was obtained in the same manner as in comparative example 1A. The cosmetic effect was evaluated by the same method as in example 1A except that PBS to which gallic acid was added in a mass ratio of 0.20% to the biocompatible film was used instead of PBS.

Examination of example 7

Table 10 shows the cultured skin permeation amount of sodium ascorbate [ mu mol/day ] after 1 day in example 7A and comparative examples 1B and 6A, and the melanin production amount [ mu g/well ] generated in the cultured skin in the two-week culture period. In addition, it was confirmed that the cell survival rate was 90% or more in both examples and comparative examples.

[ Table 10]

Watch 10

According to table 10, when the membrane carrying 2.7% of sodium ascorbate and PBS containing 0.20% of gallic acid were used, the 2 nd cyclic compound permeation amount was increased, and the melanin production amount was significantly decreased.

< example 8 >

Example 8 consisted of example 8A. In example 8, a biocompatible film in which only sodium ascorbate was supported on the film was prepared, and PBS to which menthol was added was used instead of PBS for the verification of the cosmetic effect.

< example 8A >)

In the preparation of the biocompatible film of example 1A, a biocompatible film was obtained in the same manner as in comparative example 1B. The cosmetic effect was evaluated by the same method as in example 1A except that PBS to which 0.20% by mass of menthol to the biocompatible film was added was used instead of PBS.

< comparative example 7 >

Comparative example 7 was composed of comparative example 7A. In comparative example 7, a biocompatible film was prepared, and a solution containing menthol was used instead of PBS for the purpose of cosmetic effect verification.

< comparative example 7A >)

In the preparation of the biocompatible film of example 1A, a biocompatible film was obtained in the same manner as in comparative example 1A. The evaluation was performed in the same manner as in example 1A except that a solution to which 0.20% by mass of menthol was added to the biocompatible film was used instead of PBS for the verification of the cosmetic effect.

Examination of example 8

Table 11 shows the cultured skin permeation amount of sodium ascorbate [ mu mol/day ] after 1 day in example 8A and comparative examples 1B and 7A, and the melanin production amount [ mu g/well ] generated in the cultured skin in the two-week culture period. In addition, it was confirmed that the cell survival rate was 90% or more in both examples and comparative examples.

[ Table 11]

TABLE 11

According to table 11, when the membrane carrying 2.7% of sodium ascorbate and the solution containing 0.20% of menthol were used, the 2 nd cyclic compound permeation amount was increased, and the amount of melanin produced was significantly decreased.

< example 9 >

Example 9 consisted of example 9A. In example 9, a biocompatible film in which only gallic acid was supported on the film was prepared, and PBS to which sodium ascorbate was added was used instead of PBS for the verification of the cosmetic effect.

< example 9A >)

In the preparation of the biocompatible film of example 1A, a biocompatible film was obtained in the same manner as in comparative example 1G. The cosmetic effect was evaluated by the same method as in example 1A except that PBS to which sodium ascorbate was added in a mass ratio of 3.0% to the biocompatible film was used instead of PBS.

< comparative example 8 >

Comparative example 8 was composed of comparative example 8A. In comparative example 8, a biocompatible film was prepared, and PBS to which sodium ascorbate was added was used instead of PBS for cosmetic effect verification.

< comparative example 8A >)

In the preparation of the biocompatible film of example 1A, a biocompatible film was obtained in the same manner as in comparative example 1A. The cosmetic effect was evaluated by the same method as in example 1A except that PBS to which sodium ascorbate was added in a mass ratio of 3.0% to the biocompatible film was used instead of PBS.

Examination of example 9

Table 12 shows the cultured skin permeation amount of sodium ascorbate [ mu mol/day ] after 1 day in example 9A and comparative examples 1G and 8A, and the melanin production amount [ mu G/well ] generated in the cultured skin in the two-week culture period. In addition, it was confirmed that the cell survival rate was 90% or more in both examples and comparative examples.

[ Table 12]

TABLE 12

According to table 12, when a film carrying 0.2% of gallic acid and PBS containing 3.0% of sodium ascorbate were used, the 2 nd cyclic compound permeation amount was increased, and the melanin production amount was significantly decreased.

< example 10 >

Example 10 consisted of example 10A. In example 10, a biocompatible film in which only menthol was supported on the film was prepared, and PBS to which sodium ascorbate was added was used instead of PBS for the verification of the cosmetic effect.

< example 10A >

In the preparation of the biocompatible film of example 1A, a biocompatible film was obtained in the same manner as in comparative example 1J. The evaluation was performed in the same manner as in example 1A except that PBS to which sodium ascorbate was added in a mass ratio of 3.0% to the biocompatible film was used instead of PBS for the verification of the cosmetic effect.

Examination of example 10

Table 13 shows the cultured skin permeation amount of sodium ascorbate [ mu mol/day ] after 1 day in example 10A and comparative examples 1J and 8A, and the melanin production amount [ mu g/well ] generated in the cultured skin in the two-week culture period. In addition, it was confirmed that the cell survival rate was 90% or more in both examples and comparative examples.

[ Table 13]

Watch 13

According to table 13, when a film carrying 0.2% of menthol and PBS containing 3.0% of sodium ascorbate were used, the 2 nd cyclic compound permeation amount was increased, and the amount of melanin production was significantly reduced.

< example 11 >

Example 11 consisted of example 11A. In example 11, a biocompatible film in which arbutin and gallic acid were supported on the film was prepared, and PBS was used for the verification of the cosmetic effect.

< example 11A >)

A biocompatible membrane was obtained in the same manner as in example 1A, except that arbutin was used instead of sodium ascorbate, gallic acid was used instead of sodium nicotinate, and the mass ratios of arbutin and gallic acid in the membrane to the membrane were 2.3% and 0.2%, respectively, in the preparation of the biocompatible membrane in example 1A. In the verification of the cosmetic effect, the evaluation was made by the same method as in example 1A.

< comparative example 9 >

Comparative example 9 was composed of comparative example 9A. In comparative example 9, a biocompatible film in which arbutin was supported on the film was prepared, and PBS was used for the verification of the cosmetic effect.

< comparative example 9A >)

A biocompatible film was obtained in the same manner as in example 1A, except that arbutin was used instead of sodium ascorbate so that the mass ratio of arbutin in the film to the film was 2.3% in the preparation of the biocompatible film in example 1A. In the verification of the cosmetic effect, the evaluation was made by the same method as in example 1A.

Examination of example 11

Table 14 shows the skin permeation amount [ μmol/day ] of arbutin after 1 day in example 11A and comparative examples 9A and 1G in culture, and the melanin production amount [ μ G/well ] generated in the skin in culture in the two-week culture period. In addition, it was confirmed that the cell survival rate was 90% or more in both examples and comparative examples.

[ Table 14]

TABLE t4

According to table 14, when a film carrying 2.3% of arbutin and 0.2% of gallic acid and PBS were used, the 2 nd cyclic compound permeation amount was increased, and the melanin production amount was significantly reduced.

< example 12 >

Example 12 consisted of example 12A. In example 12, a biocompatible film in which ellagic acid and gallic acid were supported on a film was prepared, and PBS was used for verification of cosmetic effects.

< example 12A >

A biocompatible membrane was obtained in the same manner as in example 1A, except that ellagic acid was used instead of sodium ascorbate and gallic acid was used instead of sodium nicotinate in the preparation of the biocompatible membrane in example 1A, and the mass ratios of ellagic acid and gallic acid in the membrane were 0.5% and 0.2%, respectively. In the verification of the cosmetic effect, the evaluation was made by the same method as in example 1A.

< comparative example 10 >

Comparative example 10 was composed of comparative example 10A. In comparative example 10, a biocompatible film in which ellagic acid was supported in the film was prepared, and PBS was used for the verification of the cosmetic effect.

< comparative example 10A >)

A biocompatible membrane was obtained in the same manner as in example 1A, except that ellagic acid was used instead of sodium ascorbate, and the mass ratio of ellagic acid in the membrane to the membrane was set to 0.5%. In the verification of the cosmetic effect, the evaluation was made by the same method as in example 1A.

Examination of example 12

Table 15 shows the cultured skin permeation amount of ellagic acid [ mu mol/day ] after 1 day of example 12A and comparative examples 10A, 1G, and the melanin production amount [ mu G/well ] generated in the cultured skin in the two-week culture period. In addition, it was confirmed that the cell survival rate was 90% or more in both examples and comparative examples.

[ Table 15]

Watch 15

According to table 15, when the membrane carrying 0.5% of ellagic acid and 0.2% of gallic acid and PBS were used, the 2 nd cyclic compound permeation amount was increased, and the amount of melanin production was significantly reduced.

< example 13 >

Example 13 consisted of example 13A. In example 13, a biocompatible film in which sodium ascorbate and syringic acid were supported on the film was prepared, and PBS was used for the verification of the cosmetic effect.

< example 13A >

A biocompatible film was obtained in the same manner as in example 1A, except that syringic acid was used instead of sodium nicotinate, the target thickness was further 2700nm, and the ascorbic acid and syringic acid in the film were supported at 9.8% and 0.9% by mass, respectively, relative to the film. The evaluation was performed by the same method as in example 1A except that PBS was used for the verification of the cosmetic effect.

Examination of example 13

Table 16 shows the cultured skin permeation amount of sodium ascorbate [ μmol/day ] after 1 day in example 13A and comparative example 1A, and the melanin production amount [ μ g/well ] generated in the cultured skin in the two-week culture period. In addition, it was confirmed that the cell survival rate was 90% or more in both examples and comparative examples.

[ Table 16]

TABLE 16

According to table 16, when the membrane supporting 9.8% of sodium ascorbate and 0.9% of syringic acid and PBS were used, the 2 nd cyclic compound permeation amount was increased, and the melanin production amount was significantly decreased.

Industrial applicability

The cosmetic or medical material of the present disclosure can be suitably used in various fields such as a cosmetic field, a medical field, and the like.

Claims

1. A cosmetic or medical material comprising:

a 1 st cyclic compound represented by the following formula (1) or a salt thereof;

a 2 nd cyclic compound or a salt thereof as an active ingredient; and

a biocompatible film which is formed by coating a biocompatible polymer,

2. The cosmetic or medical material according to claim 1, wherein the biocompatible film is capable of self-supporting and retaining at least one of the 1 st cyclic compound and the 2 nd cyclic compound.

3. The cosmetic or medical material according to claim 1 or 2, wherein the biocompatible film comprises regenerated cellulose as a main component.

4. The cosmetic or medical material according to any one of claims 1 to 3, wherein the thickness of the biocompatible film is 3 μm or less.

5. The cosmetic or medical material according to any one of claims 1 to 4, wherein the 1 st cyclic compound or a salt thereof has a larger partition coefficient than the 2 nd cyclic compound or a salt thereof.

6. The cosmetic or medical material according to any one of claims 1 to 5, wherein the 1 st cyclic compound or a salt thereof has a partition coefficient of 0 or more and 4.0 or less.

7. The cosmetic or medical material according to any one of claims 1 to 6, wherein the 1 st cyclic compound or a salt thereof has a molecular weight of 94 or more and 500 or less.

8. The cosmetic or medical material according to any one of claims 1 to 7, wherein the 1 st cyclic compound or a salt thereof comprises at least 1 selected from the group consisting of nicotinic acid, nicotinate, vanillic acid salt, ferulic acid, ferulate, pyridoxal hydrochloride, gallic acid, gallate, syringic acid and menthol.

9. The cosmetic or medical material according to any one of claims 1 to 8, wherein the 2 nd cyclic compound or a salt thereof contains at least one of a hydroxyl group and a carboxyl group.

10. The cosmetic or medical material according to any one of claims 1 to 9, wherein the 2 nd cyclic compound or a salt thereof contains at least 1 selected from ascorbic acid, sodium ascorbate, arbutin, and ellagic acid.

11. The cosmetic or medical material according to any one of claims 1 to 10, wherein the ratio of the mass of the 1 st cyclic compound or a salt thereof to the total mass of the biocompatible film supporting the 1 st cyclic compound or a salt thereof is 0.1 or more and 50 or less.

12. The cosmetic or medical material according to any one of claims 1 to 10, wherein the ratio of the mass of the 2 nd cyclic compound or a salt thereof to the total mass of the biocompatible film supporting the 2 nd cyclic compound or a salt thereof is 0.5 or more and 50 or less.

13. The cosmetic or medical material according to any one of claims 1 to 11, wherein at least one of the 1 st cyclic compound or a salt thereof and the 2 nd cyclic compound or a salt thereof is supported in the biocompatible film.

14. The cosmetic or medical material according to any one of claims 1 to 13, further comprising an aqueous solution comprising water and 1 or more kinds of polyhydric alcohols.

15. The cosmetic or medical material according to claim 14, wherein the 1 or more polyhydric alcohols are glycerin and/or propylene glycol.

16. The cosmetic or medical material according to claim 15, wherein the aqueous solution contains 5% by mass or more and 10% by mass or less of the glycerin and 5% by mass or more and 15% by mass or less of the propylene glycol.

17. A method of using a cosmetic or medical material, wherein the biocompatible film in the cosmetic or medical material according to any one of claims 1 to 16 is brought into contact with the skin.