JPWO2019171843A1 - Cosmetics or medical materials - Google Patents

Abstract

The cosmetic or medical material according to the present disclosure capable of efficiently percutaneously absorbing the active ingredient is the first cyclic compound represented by the formula (1) or a salt thereof (in the formula (1), X is CH, N, CH2 or NH, the adjacent atoms 1 to 6 are saturated or unsaturated, R1 is at least one of the carboxyl and hydroxyl groups, and R2 is the propenoic acid group. At least one selected from the group consisting of isopropyl group, methoxy group, aldehyde group, methyl group, hydroxymethyl group and hydrogen, m is an integer of 1 or more, n is an integer of 0 or more, and m The sum of n is 10 or less), a second cyclic compound as an active ingredient or a salt thereof, and a biocompatible membrane. [Chemical 1]

Description

This disclosure relates to cosmetics or medical materials.

In the fields of cosmetics, pharmaceuticals, etc., absorption of an active ingredient from a living body, for example, the skin, that is, percutaneous absorption, produces a cosmetic effect, a therapeutic or preventive effect on a disease. For example, ascorbic acid has the function of suppressing the production of collagen related to wrinkles, the production of melanin that causes sunburn and stains, and the function of reducing melanin, so that ascorbic acid penetrates into the lower layer of the epidermis of the skin where melanin is produced. If allowed, it will be effective in preventing and treating sunburn.

However, ascorbic acid is a water-soluble substance and does not easily penetrate from the surface of the skin, which is hydrophobic, to the inside of the skin. Therefore, it has been proposed to use vitamins B6 and B3, nicotinamide, and other accelerators that promote the absorption of ascorbic acid into the skin in combination. For example, Patent Documents 1 to 3 disclose external compositions containing a substance having a cosmetic effect such as ascorbic acid and a promoter such as ascorbic acid that promotes absorption into the skin.

Japanese Unexamined Patent Publication No. 6-107531 Japanese Unexamined Patent Publication No. 2006-45140 JP-A-2007-509899

Not limited to ascorbic acid, cosmetics or medical materials capable of efficiently absorbing an active ingredient into a living body, for example, the skin, are required. The present disclosure provides cosmetics or medical materials capable of efficiently transdermally absorbing an active ingredient in the fields of cosmetics, pharmaceuticals and the like.

有効成分としての第２の環式化合物またはその塩と、生体適合膜とを備える。The cosmetic or medical material of the present disclosure is a first cyclic compound represented by the following formula (1) or a salt thereof (in the formula (1), X is CH, N, CH ₂ or NH, and 1 to 6 Adjacent atoms are saturated or unsaturated, R ₁ is at least one of a carboxyl group and a hydroxyl group, and R ₂ is a propenoic acid group, an isopropyl group, a methoxy group, an aldehyde group, or a methyl group. , 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), which is at least one selected from the group consisting of hydroxymethyl groups and hydrogen.

It comprises a second cyclic compound or a salt thereof as an active ingredient, and a biocompatible membrane.

According to the present disclosure, cosmetics or medical materials capable of efficiently transdermally absorbing an active ingredient can be obtained in the fields of cosmetics, pharmaceuticals and the like.

The inventor of the present application has examined in detail the combination of an active ingredient in the cosmetic field, the pharmaceutical field, etc., which enables efficient percutaneous absorption, and an accelerator for percutaneous absorption. As a result, when both the active ingredient and the accelerator are cyclic compounds, the transdermal absorbability is improved by adding the accelerator by causing interactions such as charge transfer and hydrogen bonding between the cyclic compounds. It was found that the effect can be enhanced efficiently. The outline of the cosmetics or medical materials disclosed in the present disclosure is as follows.

（式（１）中、ＸはＣＨ、Ｎ、ＣＨ₂またはＮＨであり、１〜６の隣接する原子間は飽和結合または不飽和結合であり、Ｒ₁は、カルボキシル基およびヒドロキシル基の少なくとも一つであり、Ｒ₂は、プロペン酸基、イソプロピル基、メトキシ基、アルデヒド基、メチル基、ヒドロキシメチル基および水素からなる群より選ばれる少なくとも一つであり、ｍは１以上の整数であり、ｎは０以上の整数であって、ｍとｎの和は１０以下である）
有効成分としての第２の環式化合物またはその塩と、
生体適合膜と、
を備える。The cosmetics or medical materials of the present disclosure include the first cyclic compound represented by the following formula (1) or a salt thereof, and

(In formula (1), X is CH, N, CH ₂ or NH, the adjacent atoms 1 to 6 are saturated or unsaturated, and R ₁ is at least one of a carboxyl group and a hydroxyl group. R ₂ is at least one selected from the group consisting of propenoic acid group, isopropyl group, methoxy group, aldehyde group, methyl group, hydroxymethyl group and hydrogen, and m is an integer of 1 or more. n is an integer greater than or equal to 0, and the sum of m and n is 10 or less)
A second cyclic compound as an active ingredient or a salt thereof,
Biocompatible membrane and
To be equipped.

The cosmetics or medical materials disclosed in the present disclosure will be described in detail below.

(Composition of cosmetics or medical materials)
The cosmetics or medical materials of the present disclosure include transdermal absorption promoters, active ingredients and biocompatible membranes. Hereinafter, each component will be described in detail. When it contains an active ingredient of a cosmetic product, it may be called a cosmetic product, and when it contains an active ingredient of a pharmaceutical product, it may be called a medical material. In addition, the cosmetics or medical materials disclosed in the present disclosure include quasi-drugs and the like, which are classified between cosmetics and pharmaceuticals.

(1) Transdermal absorption promoter The transdermal absorption promoter means an agent that increases the amount of a desired component permeating into the skin. The transdermal absorption promoter of the present application is a cyclic compound as represented by the formula (1). Hereinafter, the cyclic compound which is a transdermal absorption promoter is referred to as a first cyclic compound. Further, as will be described later, a compound which is an active ingredient in the cosmetic field, the pharmaceutical field, etc., which is the target of the present application, is also a cyclic compound (hereinafter, referred to as a second cyclic compound). Therefore, the interaction between the first cyclic compound and the second cyclic compound is likely to occur, and both the first cyclic compound and the second cyclic compound are likely to penetrate into the skin. It is possible to enhance the effect of promoting transdermal absorption of the second cyclic compound.

Desirably, at least one of the first cyclic compound and the second cyclic compound is an aromatic compound, and more preferably, both the first cyclic compound and the second cyclic compound are aromatic compounds. is there. Since at least one of the first cyclic compound and the second cyclic compound is an aromatic compound, it becomes possible to utilize an interaction derived from an aromatic ring and the like, and the first cyclic compound and the second cyclic compound can be used. The interaction with the cyclic compound of the above is more likely to occur, and both the first cyclic compound and the second cyclic compound are more likely to penetrate into the skin.

Further, it is desirable that at least one of the first cyclic compound and the second cyclic compound contains a hydroxyl group, a carboxyl group, or both. By including a hydroxyl group and a carboxyl group, it becomes possible to utilize a hydrogen bond or the like for the interaction between the first cyclic compound and the second cyclic compound, and the two cyclic compounds are more likely to interact with each other. It becomes easier to penetrate the skin.

Specifically, the first cyclic compound is a cyclic compound represented by the following formula (1) or a salt thereof.

In formula (1), X is CH, N, CH ₂ or NH, the adjacent atoms 1 to 6 are saturated or unsaturated, and R ₁ is at least one of a carboxyl group and a hydroxyl group. R ₂ is at least one selected from the group consisting of a propenoic acid group, an isopropyl group, a methoxy group, an aldehyde group, a methyl group, a hydroxymethyl group and hydrogen, and m is an integer of 1 or more and n. Is an integer greater than or equal to 0, and the sum of m and n is less than or equal to 10.

In the formula (1), when m is 2 or more, that is, when 2 or more _{R 1s are present, R 1} is independently a carboxyl group or a hydroxyl group.

Further, in the formula (1), when n is 2 or more, that is, when 2 or more _{R 2 are present, R 2} is independently a propenoic acid group, an isopropyl group, a methoxy group, an aldehyde group, and a methyl group. , Hydroxymethyl group or hydrogen.

The salt of the first cyclic compound is a salt of an anion in which a proton is eliminated from the carboxyl group or hydroxyl group of the first cyclic compound and an arbitrary monovalent or polyvalent cation, or X is NH. In some cases contains hydrochloride.

The first cyclic compound represented by the formula (1) or a salt thereof may be, for example, nicotinic acid, sodium nicotinate, vanillic acid, sodium vanillate, gallic acid, ferulic acid, sodium ferrate, pyridoxal, pyridoxal hydrochloride, etc. Mentor, pyromellitic acid, mellitic acid, trimellitic acid, hydroxybenzoic acid, dihydroxybenzoic acid, hydroxyisophthalic acid, isovanic acid, cilingic acid, anisic acid, methoxysalicylic acid, trimethoxybenzoic acid, fluoroglucolcinol, methoxycatechol, resorcinol, It is at least one selected from the group consisting of pyrogallol, methoxyhydroquinone, silingic acid, and methylpyrogalol, vanillin.

The cosmetic or medical material may contain only one of the above-mentioned first cyclic compounds as a transdermal absorption promoter, or may contain two or more of them.

The molecular weight of the first cyclic compound or a salt thereof is preferably 94 or more and 500 or less. When the molecular weight is 500 or less, the size of the molecule or ion of the first cyclic compound becomes small, and the first cyclic compound easily penetrates into the skin. It is desirable that the first cyclic compound or a salt thereof has higher hydrophobicity than the second cyclic compound described later. As described above, since the first cyclic compound has a higher hydrophobicity than the second cyclic compound which is the active ingredient, the complex due to the interaction between the first cyclic compound and the second cyclic compound. The body is more hydrophobic than the second cyclic compound and is more permeable to the skin.

The hydrophobicity of the first cyclic compound can be evaluated, for example, by the partition coefficient. The partition coefficient is an actually measured value of the equilibrium solubility ratio when the compound is dissolved in two phases of water and n-octanol, and the partition coefficient P = log ₁₀ ((concentration of the compound in n-octanol) / (in water). Compound concentration)). The larger the partition coefficient P, the higher the hydrophobicity (or lipophilicity) of the compound. If the compound is more soluble in water than n-octanol, the partition coefficient takes a negative value.

The partition coefficient of the first cyclic compound is preferably 0 or more. More preferably, it is 0 or more and 4.0 or less. When the partition coefficient is 0 or more, the first cyclic compound can penetrate the skin, and when a complex is formed with the second cyclic compound, the second cyclic compound which is an active ingredient is used. Compared with the case of using it alone, it can be absorbed into the skin more. When the partition coefficient is larger than 4.0, the hydrophobicity of the first cyclic compound becomes too high, and it may be difficult to penetrate into the skin.

(2) Active ingredient As described above, the active ingredient targeted by the present application is a second cyclic compound or a salt thereof. As a result, an interaction is likely to occur between the first cyclic compound and the second cyclic compound due to less steric hindrance, etc., and both the first cyclic compound and the second cyclic compound are skin. It is thought that it will be easier to penetrate into.

As described above, it is desirable that the second cyclic compound is also an aromatic compound. Moreover, it is desirable that the second cyclic compound contains a hydroxyl group, a carboxyl group, or both. The salt of the second cyclic compound comprises a salt of an anion desorbed from a carboxyl or hydroxyl group of the second cyclic compound and any monovalent or polyvalent cation.

As the beauty effect of the second cyclic compound, for example, it may have whitening, anti-wrinkle, UV blocking, moisturizing effect and the like. Beauty ingredients that satisfy these conditions include, for example, vitamin A such as retinol, retinal, and retinoic acid, vitamin B such as thiamine, riboflavin, pyridoxin, pyridoxamine, and folic acid, and vitamin D and α such as ergocalciferol and cholecalciferol. -Vitamin E such as tocopherol, vitamins typified by vitamin K such as phylloquinone and menaquinone, vitamin A derivatives such as tretinoin and retinol palmitate, glyceryl ascorbic acid, L-ascorbic acid-2-magnesium phosphate, ascorbic acid glucoside, etc. Vitamin C derivatives, vitamin E derivatives such as α-tocopherol acetate, α-tocopheryl quinone, tocopheryl phosphate, tranexamic acid, arbutin, hydroquinone, codic acid, potassium 4-methoxysalicylate, lucinol, ellagic acid, gossipetin, mylicetin , Flavonol such as rutin, amino acids such as proline, phenylalanine, tryptophan, tyrosine, histidine and the like. Further, as the medical effect of the second cyclic compound, for example, it may have an effect such as analgesia, vasodilation, antianginal treatment, and asthma treatment. Medical ingredients that meet these conditions include, for example, acetylsalicylic acid, thialamide hydrochloride, acetaminophen, hydrocortisone, prednisolone, triamcinolone, dexamethasone, betamethasone, minoxidil, finasteride, cepharanthin, isosorbide mononitrate, isosorbide dinitrate, bisoprolol, estrone, etc. Examples thereof include estradiol and estriol.

When the cosmetics or medical materials of the present disclosure are used as cosmetics or medical materials mainly exerting effects such as whitening, the second cyclic compound consists of the group consisting of ascorbic acid, sodium ascorbic acid, arbutin, and ellagic acid. It is preferable to include at least one selected.

The active ingredient used in the present disclosure may contain one of these second cyclic compounds, or may contain two or more of the same use or two or more of different uses. Further, it may be a salt, a hydrochloride or the like of these second cyclic compounds.

The molecular weight of the second cyclic compound or a salt thereof is preferably 4000 or less. When the molecular weight is 4000 or less, the size of the molecule or ion of the second cyclic compound becomes small, and the second cyclic compound easily penetrates into the skin. Further, the molecular weight of the second cyclic compound or a salt thereof is more preferably 500 or less. When the molecular weight is 500 or less, the size of the molecule or ion of the second cyclic compound becomes smaller, and the second cyclic compound is more easily penetrated into the skin.

Further, as described above, it is desirable that the first cyclic compound has higher hydrophobicity than the second cyclic compound or a salt thereof. As a result, when the first cyclic compound, which is a transdermal absorption promoter, is used, the hydrophobicity of the complex of the first cyclic compound and the second cyclic compound becomes the second cyclic compound. It increases as compared with the simple substance, and the second cyclic compound is easily absorbed through the skin.

In particular, when the partition coefficient of the second cyclic compound is less than 0, the second cyclic compound alone is difficult to be absorbed transdermally. When such a second cyclic compound having a partition coefficient of less than 0 is used, the percutaneous absorption promoting effect of the first cyclic compound works more effectively, and absorption into the skin can be enhanced. For example, as the second cyclic compound having a partitioning coefficient of less than 0, riboflavin, pyridoxine, pyridoxamine, folic acid, glyceryl ascorbic acid, L-ascorbic acid-2-magnesium phosphate, ascorbic acid glucoside, 3-O-methyl-L- Examples thereof include ascorbic acid, tocopheryl phosphate, arbutin, kodiic acid, proline, phenylalanine, tryptophan, tyrosine, histidine, rutin, isosorbide mononitrate and the like.

Ascorbic acid is known to be effective against spots and wrinkles, for example. The molecular weight of ascorbic acid is 200 or less, but the partition coefficient is said to be -1.85. For this reason, ascorbic acid generally has low skin permeability. When ascorbic acid is used as the second cyclic compound of the cosmetic or medical material of the present disclosure, when the first cyclic compound is used and absorption into the skin is used alone, as described in the following examples. It is enhanced compared to.

(3) Biocompatible Membrane The biocompatible membrane can retain at least one of a first cyclic compound or a salt thereof and a second cyclic compound or a salt thereof. Since the biocompatible film is brought into contact with or attached to the skin or the like, it is desirable that the biocompatible film has biocompatibility. Biocompatibility means that redness, rashes, etc. are less likely to occur in living organisms such as skin, or these are less likely to occur in many subjects.

The biocompatible membrane is a first cyclic compound or a salt thereof in a solid state, a state dissolved in a suitable liquid, or a state dispersed in a gel, and a second cyclic compound or a salt thereof, as described later. It is possible to retain at least one with the salt. As a result, at least one of the first cyclic compound and the second cyclic compound can be stably maintained in contact with a living body, for example, skin.

It is desirable that the biocompatible membrane be self-supporting. Self-supporting means that the morphology of the membrane can be maintained without other supports, for example, when a part of the biocompatible membrane is pinched and lifted with a finger, tweezers, etc., the membrane is damaged. It means that it is possible to lift the whole without a support.

Biocompatible membrane materials include collagen, hyaluronic acid, polyglutamic acid, chondroitin sulfate, dermatan sulfate, keratan sulfate, heparan sulfate, heparin, chitin, chitosan, dextrin, dextrin, gluten, lignin, pectin, pullulan, xanthan gum, xylan, poly. Materials that are safe for the living body such as lactic acid, cellulose, and hydroxyethyl cellulose, which is a cellulose derivative, hydroxypropyl cellulose, carboxymethyl cellulose, methyl cellulose, and ethyl cellulose are preferable. A more preferred material is regenerated cellulose. Regenerated cellulose has a characteristic that it does not have type I crystals peculiar to natural cellulose, so that it can easily retain water appropriately and can have an excellent humidity control function. Therefore, when regenerated cellulose is attached to a living body, it is less likely to cause stuffiness or a rash while retaining an appropriate amount of water. Furthermore, it can be expected that the ability to support the first and second cyclic compounds will be enhanced by controlling the structure such as the pore and density of the regenerated cellulose.

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

The biocompatible membrane preferably has a thickness of 3 μm or less. When the thickness of the biocompatible film is 3 μm or less, there is little discomfort when placed on the skin, and wearability can be improved. In particular, the thickness of the biocompatible film is more preferably 20 nm or more and 1300 nm or less. If the thickness is 1300 nm or less, the biocompatible film can be attached to the skin without using an adhesive or an adhesive, or an adhesive layer or an adhesive layer. As a result, stuffiness and the like can be reduced without imposing a burden on the living body, and cosmetics or medical materials can be used.

The biocompatible membrane has a size depending on the use of the cosmetic or medical material and the part of the skin used. For example, the biocompatible membrane can be applied to the skin such as the face and arms. The biocompatible membrane according to the embodiments of the present disclosure typically has an area of ^{7 mm 2 or more.} When the area of the biocompatible film is 7 mm ² or more, it is possible to obtain a cosmetic effect by covering a local area of the skin such as a spot. Moreover, if a biocompatible membrane having a larger area is used, it is possible to cover the skin over a wide area. The cosmetic or medical material of the present disclosure can be applied to a living body other than the skin, and can be attached to the surface of an organ, for example, in order to enhance the healing effect of the organ.

The ratio of the mass of the first cyclic compound or its salt to the total mass of the biocompatible membrane carrying the first cyclic compound or its salt is preferably 0.1 or more and 50 mass ratio or less. When the mass ratio is 0.1 or more, the effect of promoting transdermal absorption of the first cyclic compound can be obtained, and the second cyclic compound can be effectively permeated into the skin. When the first cyclic compound is supported on the biocompatible membrane at a mass ratio of 50 or less, the biocompatible membrane maintains high strength and is stably attached to the skin.

The ratio of the mass of the second cyclic compound or its salt to the total mass of the biocompatible membrane carrying the second cyclic compound or its salt is preferably 0.5 or more and 50 mass ratio or less. When the mass ratio is 0.5 or more, the second cyclic compound can be effectively penetrated into the skin. When the second cyclic compound is supported on the biocompatible membrane at a mass ratio of 50 or less, the biocompatible membrane maintains high strength and is stably attached to the skin.

(4) Mounting Liquid When at least one of the first cyclic compound and the second cyclic compound is a solid, the first cyclic compound and the second cyclic compound are uniformly supported on the biocompatible membrane. The cosmetic or medical material may further comprise a mounting solution to allow the biocompatible membrane to adhere to the placed skin. As the mounting liquid, a liquid that is safe for the living body can be used. For example, the mounting liquid contains one or more selected from pure water, physiological saline, an aqueous solution of a lotion, a beauty essence, etc., a lotion containing an organic solvent, a milky lotion, a beauty essence, a cream, and the like. Desirably, the mounting solution comprises water and a polyhydric alcohol. Examples of the polyhydric alcohol include glycerol and propanediol, and the mounting solution may contain both glycerol and propanediol. Since the polyhydric alcohol is slightly more hydrophobic than water, the mounting solution containing water and the polyhydric alcohol can dissolve both the first cyclic compound and the second cyclic compound. As a result, the first cyclic compound and the second cyclic compound are uniformly arranged in the biocompatible membrane, the first cyclic compound and the second cyclic compound interact with each other, and the complex is formed on the skin. It becomes possible to penetrate into.

It is desirable that the concentration of the mounting solution contains, for example, 5% by mass or more and 10% by mass or less of glycerol, 5% by mass or more and 15% by mass or less of propanediol, and the balance of water. Since the mounting solution having this composition is less irritating to the skin and the like, the biocompatible film containing the mounting solution can be easily mounted for a long time.

(5) Other Ingredients Ingredients of cosmetics or medical materials other than the first cyclic compound and the second cyclic compound may be contained. For example, as ingredients of cosmetics, hyaluronic acid, ceramide, collagen, amino acid, 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, fatty acid polyglyceryl, polyglycerin, jojoba oil, trimethylglycin, mannitol, trehalose, glycosyl trehalose, purulan, erythritol, elastin, dipropylene Glycol, butylene glycol, ethyl ethylhexanoate, sodium acrylate, disodium edetate, sucrose fatty acid ester, squalane, polyethylene glycol, polyoxyethylene hydrogenated castor oil, glycerin stearate, ethanol, polyvinyl alcohol, hydroxyethyl cellulose, ectin, etc. Can be mentioned. In addition, as components of medical materials, isosorbide nitrate, indomethacin, diflucortron valerate, acyclovir, ketoconazole, ketoprofen, diclofenac sodium, dexamethasone propionic acid ester, felbinac, clobetazol propionic acid ester, loxoprofen, methyl salicylate, tacrolimus, etc. Can be mentioned.

(Aspects of cosmetics or medical materials)
Cosmetics or medical materials can be composed of various aspects.

(1) Supporting First and Second Cyclic Compounds on Biocompatible Membrane The first cyclic compound and the second cyclic compound may be supported on the biocompatible membrane in advance. When the first cyclic compound and the second cyclic compound are solid at room temperature, the first cyclic compound and the second cyclic compound can be supported on the biocompatible membrane in the solid state. For example, when the second cyclic compound is ascorbic acid, the reduced form is considered to have cosmetic effects such as suppression of melanin production, hyaluronic acid synthesis, and UV protection. However, ascorbic acid easily changes from the reduced form to the oxidized form in an aqueous solution. Therefore, when reduced ascorbic acid as the second cyclic compound is supported on the biocompatible membrane in a solid state, it is less likely to be oxidized. Similarly, the first cyclic compound is supported in a solid state. This makes it possible to stably hold the first cyclic compound and the second cyclic compound for a long period of time.

The first and second cyclic compounds may be supported on the biocompatible membrane or may be supported on the surface of the biocompatible membrane. In order to prevent the first and second cyclic compounds from being removed by friction or the like, it is desirable that the first and second cyclic compounds are supported in the biocompatible membrane.

(2) One of the first and second cyclic compounds is supported on the biocompatible membrane One of the first cyclic compound and the second cyclic compound may be supported on the biocompatible membrane in advance. The other of the first cyclic compound and the second cyclic compound are two when using cosmetics or medical materials, for example, by dissolving the other in a mounting solution and including the mounting solution in a biocompatible membrane. The cyclic compound may be placed on a biocompatible membrane. Further, for example, when there is an adverse effect such as decomposition due to strong interaction between the first cyclic compound and the second cyclic compound, one of them is supported on a biocompatible membrane for the purpose of separating and holding it. It does not have to be.

(3) Placement of First and Second Cyclic Compounds Afterwards The first and second cyclic compounds may be stored separately from the biocompatible membrane. That is, both the first cyclic compound and the second cyclic compound may not be supported on the biocompatible membrane and may be placed on the biocompatible membrane at the time of use. In this case, for example, at the time of use, the first cyclic compound and the second cyclic compound may be dissolved in the mounting solution, and the mounting solution in which the two cyclic compounds are dissolved may be placed on the biocompatible membrane by dropping or the like. Good. Alternatively, a first mounting solution and a second mounting solution in which the first cyclic compound and the second cyclic compound are dissolved are prepared, respectively, and the first mounting solution and the second mounting solution are used as a living body at the time of use. It may be arranged by dropping it on a compatible film. In these forms, the first cyclic compound and the second cyclic compound can be more arranged on the skin surface as compared with the case of being supported on the biocompatible membrane, and the amount of penetration into the skin can be improved. May be possible.

(How to use cosmetics or medical materials)
The cosmetics or medical materials of the present disclosure are used by holding a first cyclic compound or a salt thereof and a second cyclic compound or a salt thereof on a biocompatible film and bringing the biocompatible film into contact with the skin. To do. When the biocompatible film is brought into contact with the skin and used, it is sufficient that the first cyclic compound or a salt thereof and the second cyclic compound or a salt thereof are retained in the biocompatible film, and the cosmetics of the present disclosure The material or medical material may be any of the above-mentioned aspects (1) to (3). The methods of using the cosmetics or medical materials disclosed in the present disclosure are classified into the following three types according to the timing of arranging the mounting solution. When any of the above three usage modes is used, the mounting solution can be arranged at the following three types of timings.
(1) When dripping on the skin First, the mounting solution is dropped on the surface of the skin, and a biocompatible film is attached to the skin so as to cover the dropped mounting solution.
(2) When dropping on a biocompatible membrane First, the mounting solution is impregnated in the biocompatible membrane, and the biocompatible membrane containing the mounting liquid is attached to the skin.
(3) When dropping on the biocompatible membrane placed on the skin The biocompatible membrane is first placed on the skin, and the mounting solution is dropped on the biocompatible membrane.

Regardless of which of these timings the mounting solution is used, the biocompatible membrane can stably maintain the state in which the skin and the mounting solution are in contact with each other. Therefore, the first cyclic compound and the second cyclic compound in the mounting solution can be stably percutaneously absorbed into the skin for a long time in a state of interaction.

(effect)
According to the cosmetics or medical materials of the present disclosure, the first cyclic compound represented by the formula (1) or a salt thereof and the second cyclic compound as an active ingredient or a salt thereof have a ring structure. Therefore, the interaction between the first cyclic compound and the second cyclic compound is likely to occur, and both the first cyclic compound and the second cyclic compound are likely to penetrate into the skin. Further, the cyclic compound represented by the formula (1) is a substance having a relatively large partition coefficient and easily absorbed through the skin. Therefore, even if the second cyclic compound is water-soluble, that is, the distribution coefficient of the second cyclic compound is small and it is difficult to be absorbed through the skin, a complex is formed with the first cyclic compound. By doing so, it becomes easy to be absorbed through the skin, and the second cyclic compound can be effectively penetrated into the skin.

Further, the cosmetic or medical material of the present disclosure comprises a biocompatible film, and the biocompatible film includes, for example, a first cyclic compound or a salt thereof dissolved in a liquid and a second cyclic compound or a salt thereof. And can be stably held. Since the biocompatible film is hypoallergenic, it is possible to realize a cosmetic or medical material that can be applied to the skin for a period of time depending on the application.

(Manufacturing method of cosmetics or medical materials)
(1) First Cyclic Compound and Second Cyclic Compound The first cyclic compound and the second cyclic compound are commercially available products having purity and safety for a subject as required for use and need. Can be used.

(2) Mounting solution The mounting solution is pure water, physiological saline, an aqueous solution of a commercially available lotion, a beauty essence, etc., a lotion containing an organic solvent, a milky lotion, a beauty essence, a cream, etc., or a first cyclic compound. A solution containing a beauty / medical ingredient and the like, and a solution obtained by mixing the above-mentioned polyhydric alcohol in the above-mentioned ratio.

(3) Biocompatible Membrane A biocompatible membrane 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 cellulose used preferably has a weight average molecular weight of 30,000 or more. Further, when cellulose having a weight average molecular weight of 150,000 or more is used, a biocompatible film having a thickness of 1300 nm (1.3 μm) or less can be stably obtained.

As the cellulose, as long as it has a predetermined weight average molecular weight, cellulose derived from a plant such as pulp or cotton, or cellulose produced by an organism such as a bacterium can be used. It is beneficial that the impurity concentration of cellulose as a raw material is 10 wt% or less.

As the solvent, a solvent containing an ionic liquid may be used. Cellulose can be dissolved in a relatively short time by using a solvent containing at least an ionic liquid. An ionic liquid is a salt composed of anions and cations, and can exhibit a liquid state at a temperature of 150 ° C. or lower. As the ionic liquid that dissolves cellulose, an ionic liquid containing an amino acid or an alkyl phosphate 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 existing in the living body, it can be said that an ionic liquid containing amino acids makes it possible to produce a regenerated biocompatible membrane that is safer for the living body.

As the ionic liquid that dissolves 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. As can be seen from the general formula (s1), in this example, the anion contains a terminal carboxyl group and a terminal amino group. The cation of the ionic liquid represented by the general formula (s1) may be a quaternary ammonium cation.

In the general formula (s1), R _{1 to} R ₆ independently represent a hydrogen atom or a substituent. The substituent can be an alkyl group, a hydroxyalkyl group or a phenyl group, and may contain a branch in the carbon chain. The substituent may contain an amino group, a hydroxyl group, a carboxyl group and the like. n is an integer of 1 or more and 5 or less.

Alternatively, as the ionic liquid that dissolves cellulose, an ionic liquid represented by the following general formula (s2) can also be used. In the general formula (s2) below, R ₁ , R ₂ , R ₃ and R ₄ independently represent a hydrogen atom or an alkyl group having 1 to 4 carbon atoms (C _{1 −} C _4).

The obtained cellulose solution is 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 that does not dissolve cellulose (hereinafter, may be referred to as “rinse liquid”). This step may be said to be a step of cleaning the polymer gel sheet, which removes the solvent containing the ionic liquid from the polymer gel sheet.

As the liquid (rinse liquid) in which the polymer gel sheet is immersed, a solvent that can be dissolved in at least an ionic liquid can be used. Examples of such liquids are water, methanol, ethanol, propanol, butanol, octanol, toluene, xylene, acetone, acetonitrile, dimethylacetamide, dimethylformamide, dimethyl sulfoxide.

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

When at least one of the first cyclic compound and the second cyclic compound is supported on the biocompatible membrane, for example, before and / or after removing the above-mentioned solvent and rinsing solution from the polymer gel sheet, the first The obtained biocompatible film is immersed in a solution in which at least one of the first cyclic compound and the second cyclic compound is dissolved, and the biocompatible film is taken out from the solution and dried. As a result, a biocompatible membrane on which at least one of the first cyclic compound and the second cyclic compound is supported is obtained.

Examples of the solvent for dissolving the first cyclic compound and the second cyclic compound include water, ethanol, propanol, butanol, acetone, glycerol, propanediol, 1,3-butanediol, 1,4-butanediol, and di. Examples thereof include glycerin, polyethylene glycol and dimethicone. Moreover, you may use a plurality of these solutions. Further, the sheet may be impregnated with a solution containing components for beauty / medical use and supported, or the components for beauty / medical use may be supported by spraying, vapor deposition or the like.

In the same manner, active ingredients and the like other than the first cyclic compound and the second cyclic compound can be supported on the biocompatible membrane.

(Example)
Hereinafter, examples of the cosmetics or medical materials disclosed in the present disclosure will be described.

In the examples, the compounds shown in Tables 1 to 3 below were used as the first cyclic compound and the second cyclic compound. As a comparative example, Table 2 shows nicotinamide and leucine acid used in place of the first cyclic compound. In the following examples, the second cyclic compound may be referred to as a cosmetological agent.

(1) Example 1
Example 1 is composed of Examples 1A to 1I. In Example 1, ascorbic acid or sodium ascorbate as the second cyclic compound and nicotinic acid or sodium nicotinate or gallic acid or sodium ferlate or pyridoxal hydrochloride or menthol as the first cyclic compound in the membrane. A supported biocompatible membrane was used.

<Example 1A>
(Preparation of biocompatible membrane)
Cellulose derived from bleached pulp made from wood having a purity of 90% or more was dissolved in an ionic liquid to prepare a cellulose solution. As the ionic liquid, an ionic liquid having R ₁ as a methyl group and R _{2 to} R ₄ as an ethyl group in the formula (s2) was used. A polymer gel sheet was formed by applying a cellulose solution on the substrate. At this time, the coating thickness was adjusted so that the thickness of the biocompatible film was the target thickness of 900 nm. Cleaning of the substrate and polymer gel sheet was performed.

Furthermore, by immersing the washed polymer gel sheet in a solution of sodium ascorbate and sodium nicotinate in water and drying it, the mass ratio of sodium ascorbate to the membrane was 2.7% and sodium nicotinate 0. A biocompatible membrane carrying the first cyclic compound and the second cyclic compound of Example 1A, carrying .2%, was obtained. The film had a shape of approximately 5 cm square and a transparent appearance.

(Method for quantifying the second cyclic compound and the first cyclic compound in the membrane)
The mass ratio of sodium ascorbate and sodium nicotinate in the membrane to the membrane was obtained by the following method. Sodium nicotinate was dissolved in ultrapure water in advance, and calibration curves were drawn for the concentration and absorbance at _{266 and 220} nm measured with an absorptiometer UV-1600 (Shimadzu Seisakusho), respectively, to obtain slopes a 266 and a 220, respectively. It was. Similarly, sodium ascorbate was dissolved in ultrapure water, and a calibration curve was drawn for its concentration and absorbance at 266 nm to obtain a _{slope b 266.} The membrane was immersed in ultrapure water, the nicotinic acid concentration C _N in the solution extracted from 220nm absorbance I ₂₂₀ of a solution obtained by extracting the components of 1 hour film ultrasonically was determined using the calibration curve. Further, to obtain the extracted sodium ascorbate in the film by dividing the amount of solution L and multiplied film mass W mass ratio D _N. That is, it becomes as follows.

On the other hand, for sodium ascorbate, the concentration of sodium ascorbate cannot be calculated as it is because a part of the spectrum of sodium ascorbate and sodium nicotinate is covered. Therefore, first, the absorbance I ₂₆₆ of the extracted liquid was obtained. Then, sodium resulting nicotinic acid concentration C _N was calculated absorbance I _N266 of 266nm with sodium nicotinate. Using these values and b _266, Formula (III), to give ascorbic acid concentration by using (IV) C _A, and the mass ratio D _N of sodium ascorbate in the film.

(Verification of cosmetological effect by cultured skin of biocompatible membrane holding the second cyclic compound)
As a three-dimensional cultured epidermis model containing melanocytes, MEL-300A (Kurabo Industries Ltd., hereinafter referred to as MEL) was used. During the culture test _{, maintenance and culture were carried out in a CO 2} incubator (37 degrees, 5% CO ₂ ) using EPI-100LLMM long-term maintenance medium (Kurabo Industries Ltd., hereinafter EPI). After transferring the MEL to the plate, preculture was performed with 2 ml of EPI. The MEL was then transferred to a plate supplemented with 5 ml EPI. The membrane of Example 1A was placed on the keratin side of the MEL, and the membrane surface was moistened with phosphate buffered saline (PBS). The EPI was replaced 1 day after membrane placement and once every 2 days thereafter, and the biocompatible membrane and PBS were replaced once every 4 days.

Except for using the EPI cultured skin permeation concentration P _A of sodium ascorbate 1 day after the film installation instead of ultra pure water, (quantification method of the second cyclic compound and the first cyclic compounds in the film) It was obtained in the same manner using the formulas (I) to (III) of. From the solution amount V _EPI of cultured skin permeation concentration of the resulting sodium ascorbate P _A and EPI with Formula (V), at determined cultured skin permeation amount M _A of sodium ascorbate after 1 day.

After continuous culturing for 2 weeks, the cell viability of MEL was determined by the Alamar blue method. A solution prepared by adding 0.20 g Alamar Blue (Cosmo Bio Co., Ltd.) to 1.8 g EPI was added dropwise to a plate, and MEL was placed. After culturing for 2 hours, the fluorescence intensity of the medium supernatant (excitation wavelength 544 nm, measurement wavelength 590 nm) was measured with a spectrofluorometer FP-8500 (JASCO). The cell viability was calculated as a ratio to the fluorescence intensity when the membrane of Comparative Example 1A described later was added.

After washing the MEL with PBS, the cultured skin site was cut out from the MEL and transferred to a glass bottle. Then, ethanol and diethyl ether were replaced with a solution having an equal mass ratio and then with diethyl ether for more than half a day. The washed cultured skin site was immersed in a 1 M aqueous sodium hydroxide solution to dissolve melanin in the cultured skin. The melanin content in the cultured skin was calculated in advance by measuring the absorbance at 405 nm with an absorptiometer UV-1600 (Shimadzu Seisakusho) and using a calibration curve based on the dissolution concentration and absorbance of synthetic melanin (Sigma Aldrich Japan Co., Ltd.).

<Example 1B>
In the preparation of the biocompatible membrane of Example 1A, a cosmetic ingredient solution in which sodium ascorbate and nicotinic acid were dissolved was used to carry 2.6% sodium ascorbate and 0.2% nicotinic acid as a mass ratio to the membrane. A film was obtained in the same manner as in Example 1A, except that the film was allowed to grow. The beauty effect verification was also evaluated by the same method as in Example 1A.

<Example 1C>
In the preparation of the biocompatible membrane of Example 1A, a cosmetic ingredient solution in which ascorbic acid and sodium nicotinate was dissolved was used to support 2.6% ascorbic acid and 0.2% sodium nicotinate as a mass ratio to the membrane. A film was obtained in the same manner as in Example 1A, except that the film was allowed to grow. The beauty effect verification was also evaluated by the same method as in Example 1A.

<Example 1D>
In the preparation of the biocompatible membrane of Example 1A, a membrane carrying 2.7% ascorbic acid and 0.2% nicotinic acid as a mass ratio to the membrane using a cosmetic ingredient solution in which ascorbic acid and nicotinic acid were dissolved. A film was obtained in the same manner as in Example 1A except that The beauty effect verification was also evaluated by the same method as in Example 1A.

<Example 1E>
In the preparation of the biocompatible membrane of Example 1A, using a cosmetic ingredient solution in which sodium ascorbate and sodium vanitate were dissolved, 2.7% sodium ascorbate and 0.2% sodium vanitate were used as mass ratios to the membrane. A film was obtained in the same manner as in Example 1A, except that The beauty effect verification was also evaluated by the same method as in Example 1A.

<Example 1F>
In the preparation of the biocompatible membrane of Example 1A, a cosmetic ingredient solution in which sodium ascorbic acid and gallic acid were dissolved was used to carry 2.7% sodium ascorbate and 0.2% gallic acid as a mass ratio to the membrane. A film was obtained in the same manner as in Example 1A except that. The beauty effect verification was also evaluated by the same method as in Example 1A.

<Example 1G>
In the preparation of the biocompatible membrane of Example 1A, a beauty ingredient solution in which sodium ascorbate and sodium ferlate were dissolved was used, and the mass ratios to the membrane were 2.7% sodium ascorbate and 0.2% sodium ferlate. A film was obtained in the same manner as in Example 1A, except that The beauty effect verification was also evaluated by the same method as in Example 1A.

<Example 1H>
In the preparation of the biocompatible membrane of Example 1A, using a cosmetic ingredient solution in which sodium ascorbate and pyridoxal hydrochloride were dissolved, 2.7% sodium ascorbate and 0.2% pyridoxal hydrochloride were used as the mass ratio to the membrane. A film was obtained in the same manner as in Example 1A, except that The beauty effect verification was also evaluated by the same method as in Example 1A.

<Example 1I>
In the preparation of the biocompatible membrane of Example 1A, the washed polymer gel sheet was used as a beauty ingredient solution in which sodium ascorbate and menthol were dissolved, and the mass ratio to the membrane was 2.7% sodium ascorbate and 0. A film was obtained in the same manner as in Example 1A except that 2% menthol was supported. Sodium ascorbate in the membrane was determined by the same method as in Example 1A (method for quantifying the second cyclic compound and the first cyclic compound in the membrane), and ascorbate was determined from the reaction amount using anhydrous acetic acid. The amount of menthol in the membrane was determined by subtracting the amount required for sodium ascorbate. The beauty effect verification was also evaluated by the same method as in Example 1A.

<Comparative example 1>
Comparative Example 1 is composed of Comparative Example 1A to Comparative Example 1N. In Comparative Example 1, a biocompatible membrane without a carrier, or a supported biocompatible membrane containing only a second cyclic compound or a first cyclic compound was used.

<Comparative Example 1A>
In the preparation of the biocompatible film of Example 1A, a biocompatible film was obtained in the same manner as in Example 1A except that it was not immersed in the beauty ingredient solution. The beauty effect verification was also evaluated by the same method as in Example 1A.

<Comparative Example 1B>
In the preparation of the biocompatible membrane of Example 1A, the same as in Example 1A except that 2.7% sodium ascorbate was supported as a mass ratio to the membrane by using a cosmetic ingredient solution in which sodium ascorbate was dissolved. I got a film. The beauty effect verification was also evaluated by the same method as in Example 1A.

<Comparative Example 1C>
In the preparation of the biocompatible membrane of Example 1A, a membrane in the same manner as in Example 1A except that 2.6% ascorbic acid was supported as a mass ratio to the membrane by using a cosmetic ingredient solution in which ascorbic acid was dissolved. Got The beauty effect verification was also evaluated by the same method as in Example 1A.

<Comparative Example 1D>
In the preparation of the biocompatible membrane of Example 1A, the same as in Example 1A except that 0.2% sodium nicotinate was supported as a mass ratio to the membrane by using a cosmetic ingredient solution in which sodium nicotinate was dissolved. I got a film. The beauty effect verification was also evaluated by the same method as in Example 1A.

<Comparative Example 1E>
In the preparation of the biocompatible film of Example 1A, a film was used in the same manner as in Example 1A except that 0.2% nicotinic acid was supported as a mass ratio to the film by using a beauty ingredient solution in which nicotinic acid was dissolved. Got The beauty effect verification was also evaluated by the same method as in Example 1A.

<Comparative example 1F>
In the preparation of the biocompatible membrane of Example 1A, the same as in Example 1A except that a beauty ingredient solution in which sodium vanillate was dissolved was used to support 0.2% sodium vanillate as a mass ratio to the membrane. I got a film. The beauty effect verification was also evaluated by the same method as in Example 1A.

<Comparative example 1G>
In the preparation of the biocompatible membrane of Example 1A, a membrane in the same manner as in Example 1A except that 0.2% gallic acid was supported as a mass ratio to the membrane by using a beauty ingredient solution in which gallic acid was dissolved. Got The beauty effect verification was also evaluated by the same method as in Example 1A.

<Comparative Example 1H>
In the preparation of the biocompatible membrane of Example 1A, the same as in Example 1A except that 0.2% sodium ferulate was supported as a mass ratio to the membrane by using a cosmetic ingredient solution in which sodium ferulate was dissolved. Obtained a film. The beauty effect verification was also evaluated by the same method as in Example 1A.

<Comparative Example 1I>
In the preparation of the biocompatible membrane of Example 1A, the same as in Example 1A except that 0.2% pyridoxal hydrochloride was supported as a mass ratio to the membrane by using a beauty ingredient solution in which pyridoxal hydrochloride was dissolved. I got a film. The beauty effect verification was also evaluated by the same method as in Example 1A.

<Comparative Example 1J>
In the preparation of the biocompatible membrane of Example 1A, a membrane was obtained in the same manner as in Example 1A except that 0.2% menthol was supported as a mass ratio to the membrane by using a beauty ingredient solution in which menthol was dissolved. It was. The beauty effect verification was also evaluated by the same method as in Example 1A.

<Comparative example 1K>
In the preparation of the biocompatible membrane of Example 1A, a cosmetic ingredient solution in which sodium ascorbate and nicotinamide were dissolved was used to carry 2.7% sodium ascorbate and 0.2% nicotinamide as a mass ratio to the membrane. A film was obtained in the same manner as in Example 1A except that. The beauty effect verification was also evaluated by the same method as in Example 1A.

<Comparative Example 1L>
In the preparation of the biocompatible membrane of Example 1A, a membrane in the same manner as in Example 1A except that 0.2% nicotinamide was supported as a mass ratio to the membrane by using a cosmetic ingredient solution in which nicotinamide was dissolved. Got The beauty effect verification was also evaluated by the same method as in Example 1A.

<Comparative Example 1M>
In the preparation of the biocompatible membrane of Example 1A, a beauty ingredient solution in which sodium ascorbate and leucine acid were dissolved was used to support 2.7% sodium ascorbate and 0.2% leucine acid as a mass ratio to the membrane. A film was obtained in the same manner as in Example 1A except that. The beauty effect verification was also evaluated by the same method as in Example 1A.

<Comparative Example 1N>
In the preparation of the biocompatible membrane of Example 1A, a membrane in the same manner as in Example 1A except that 0.2% leucine acid was supported as a mass ratio to the membrane by using a beauty ingredient solution in which leucine acid was dissolved. Got The beauty effect verification was also evaluated by the same method as in Example 1A.

<Discussion of Example 1>
Table 4 shows the permeation amount [μmol / day] of ascorbic acid or sodium ascorbic acid in the cultured skin one day after Examples 1A to 1I and Comparative Examples 1A to 1N, and the melanin produced in the cultured skin during the two-week culture period. The output [μg / well] was shown. It was confirmed that the cell viability was 90% or more in both Examples and Comparative Examples.

According to Table 4, when Example 1A and Comparative Examples 1A, 1B and 1D are compared, the second cyclic compound (cosmetological agent) is supported by carrying 2.7% sodium ascorbate and 0.2% sodium nicotinate. The amount of permeation was dramatically improved, and the amount of melanin produced was reduced.

Comparing Example 1B with Comparative Examples 1A, 1B, and 1E, the support of 2.6% sodium ascorbate and 0.2% nicotinic acid dramatically improved the permeation amount of the second cyclic compound and produced melanin. The amount was reduced.

Comparing Example 1C with Comparative Examples 1A, 1C and 1D, the support of 2.6% ascorbic acid and 0.2% sodium nicotinate dramatically improved the permeation amount of the second cyclic compound and produced melanin. The amount was reduced.

Comparing Example 1D and Comparative Examples 1A, 1C, and 1E, the support of 2.7% ascorbic acid and 0.2% nicotinic acid dramatically improves the permeation amount of the second cyclic compound and produces melanin. Was lowered.

Comparing Example 1E and Comparative Examples 1A, 1B, and 1F, the carrying of 2.7% sodium ascorbate and 0.2% sodium vanillate dramatically improved the permeation amount of the second cyclic compound and melanin. The output was reduced.

Comparing Example 1F and Comparative Examples 1A, 1B, and 1G, the support of 2.7% sodium ascorbate and 0.2% gallic acid dramatically improved the permeation amount of the second cyclic compound and melanin. The output was reduced.

Comparing Example 1G with Comparative Examples 1A, 1B, and 1H, the support of 2.7% sodium ascorbate and 0.2% sodium ferulate dramatically improved the permeation amount of the second cyclic compound. The amount of melanin produced was reduced.

Comparing Example 1H with Comparative Examples 1A, 1B, and 1I, the support of 2.7% sodium ascorbate and 0.2% pyridoxal hydrochloride dramatically improved the permeation amount of the second cyclic compound. The amount of melanin produced was reduced.

Comparing Example 1I and Comparative Examples 1A, 1B, and 1J, the support of 2.7% sodium ascorbate and 0.2% menthol dramatically improved the permeation amount of the second cyclic compound and produced melanin. The amount was reduced.

Comparing Comparative Example 1K and Comparative Examples 1A, 1B, and 1L, the support of 2.7% sodium ascorbate and 0.2% nicotinamide did not improve the permeation amount of the second cyclic compound, and the amount of melanin produced. It turns out that it was not possible to reduce.

Comparing Comparative Example 1M and Comparative Examples 1A, 1B, and 1N, the support of 2.7% sodium ascorbate and 0.2% leucine acid did not improve the permeation amount of the second cyclic compound, and the amount of melanin produced. It turns out that it was not possible to reduce.

Based on the above, by using sodium nicotinate, nicotinic acid, sodium vanillate, ascorbic acid, sodium ferulate, pyridoxal hydrochloride, and menthol as the first cyclic compound, the second cyclic compound (beauty agent) can be used. The permeation amount of ascorbic acid and sodium ascorbic acid into the cultured skin is dramatically increased, and the amount of melanin produced in the cultured skin can be suppressed.

<Example 2>
Example 2 is composed of Example 2A-2G. The amount of reduced sodium ascorbic acid in the biocompatible membrane prepared in Example 1 over a long period of time was investigated.

<Example 2A>
In the preparation of the biocompatible membrane of Example 1A, a biocompatible membrane was obtained in the same manner as in Example 1A. The biocompatible membrane stored for 1 week and 4 weeks under the initial conditions and 20 ° C. conditions was immersed in 2 g of ultrapure water and ultrasonically washed for 1 hour. The amount of reduced ascorbic acid in the solution was quantified by an ascorbic acid quantification kit (BioVision), standardized by the amount of sodium ascorbic acid contained in the initial membrane, and the ratio of reduced ascorbic acid was determined.

<Example 2B>
In the preparation of the biocompatible membrane of Example 1A, a biocompatible membrane was obtained in the same manner as in Example 1B. In the same manner as in Example 2A, the ratio of reduced ascorbic acid after storage for 1 week and 4 weeks with respect to the initial stage was determined.

<Example 2C>
In the preparation of the biocompatible membrane of Example 1A, a biocompatible membrane was obtained in the same manner as in Example 1E. In the same manner as in Example 2A, the ratio of reduced ascorbic acid after storage for 1 week and 4 weeks with respect to the initial stage was determined.

<Example 2D>
In the preparation of the biocompatible membrane of Example 1A, a biocompatible membrane was obtained in the same manner as in Example 1F. In the same manner as in Example 2A, the ratio of reduced ascorbic acid after storage for 1 week and 4 weeks with respect to the initial stage was determined.

<Example 2E>
In the preparation of the biocompatible membrane of Example 1A, a biocompatible membrane was obtained in the same manner as in Example 1G. In the same manner as in Example 2A, the ratio of reduced ascorbic acid after storage for 1 week and 4 weeks with respect to the initial stage was determined.

<Example 2F>
In the preparation of the biocompatible membrane of Example 1A, a biocompatible membrane was obtained in the same manner as in Example 1H. In the same manner as in Example 2A, the ratio of reduced ascorbic acid after storage for 1 week and 4 weeks with respect to the initial stage was determined.

<Example 2G>
In the preparation of the biocompatible membrane of Example 1A, a biocompatible membrane was obtained in the same manner as in Example 1I. In the same manner as in Example 2A, the ratio of reduced ascorbic acid after storage for 1 week and 4 weeks with respect to the initial stage was determined.

<Comparative example 2>
Comparative Example 2 is composed of Comparative Example 2A-2G. It was composed of an aqueous solution in which sodium ascorbic acid and the first cyclic compound were dissolved, and the amount of reduced ascorbic acid was quantified.

<Comparative Example 2A>
PBS was prepared by dissolving sodium ascorbate and sodium nicotinate in a mass ratio of 3.0% and 0.2%, respectively, with respect to the solution. After vibrating the solution and allowing the aqueous solution to contain sufficient air, the solution was stored under 20 ° C. conditions for 1 week and 4 weeks. In the same manner as in Example 1A, the ratio of reduced ascorbic acid after storage for 1 week and 4 weeks with respect to the initial stage was determined.

<Comparative Example 2B>
An aqueous solution was prepared in the same manner as in Comparative Example 2A except that PBS in which sodium ascorbate and nicotinic acid were dissolved in a mass ratio of 3.0% and 0.2%, respectively, with respect to the solution was prepared. In the same manner as in Example 1A, the ratio of reduced ascorbic acid after storage for 1 week and 4 weeks with respect to the initial stage was determined.

<Comparative Example 2C>
An aqueous solution was prepared in the same manner as in Comparative Example 2A, except that PBS was prepared by dissolving sodium ascorbate and sodium vanillate in a mass ratio of 3.0% and 0.2% to the solution, respectively. In the same manner as in Example 1A, the ratio of reduced ascorbic acid after storage for 1 week and 4 weeks with respect to the initial stage was determined.

<Comparative example 2D>
An aqueous solution was prepared in the same manner as in Comparative Example 2A except that PBS in which sodium ascorbate and gallic acid were dissolved in a mass ratio of 3.0% and 0.2% to the solution was prepared. In the same manner as in Example 1A, the ratio of reduced ascorbic acid after storage for 1 week and 4 weeks with respect to the initial stage was determined.

<Comparative Example 2E>
An aqueous solution was prepared in the same manner as in Comparative Example 2A, except that PBS in which sodium ascorbate and sodium ferulate were dissolved in a mass ratio of 3.0% and 0.2% to the solution was prepared. In the same manner as in Example 1A, the ratio of reduced ascorbic acid after storage for 1 week and 4 weeks with respect to the initial stage was determined.

<Comparative example 2F>
An aqueous solution was prepared in the same manner as in Comparative Example 2A except that PBS in which sodium ascorbate and pyridoxal hydrochloride were dissolved in a mass ratio of 3.0% and 0.2%, respectively, with respect to the solution was prepared. In the same manner as in Example 1A, the ratio of reduced ascorbic acid after storage for 1 week and 4 weeks with respect to the initial stage was determined.

<Comparative example 2G>
An aqueous solution was prepared in the same manner as in Comparative Example 2A, except that PBS in which sodium ascorbate and menthol were dissolved in a mass ratio of 3.0% and 0.2% to the solution was prepared. In the same manner as in Example 1A, the ratio of reduced ascorbic acid after storage for 1 week and 4 weeks with respect to the initial stage was determined.

<Discussion of Example 2>
Table 5 shows the ratio of the amount of reduced ascorbic acid to the initial amount of Example 2A-2F and Comparative Example 2A-2F after 1 week and 4 weeks.

According to Table 5, reduced ascorbic acid could be stably maintained for at least 4 weeks 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 was supported as the second cyclic compound and sodium nicotinate was supported in the membrane as the first cyclic compound was used.

<Example 3A>
In the preparation of the biocompatible membrane of Example 1A, a cosmetic ingredient solution in which sodium ascorbate and sodium nicotinate were dissolved was used, and the mass ratios to the membrane were 0.5% sodium ascorbate and 0.1% sodium nicotinate. A film was obtained in the same manner as in Example 1A, except that The beauty effect verification was also evaluated by the same method as in Example 1A.

<Example 3B>
In the preparation of the biocompatible membrane of Example 1A, the washed polymer gel sheet was immersed in a beauty ingredient solution in which sodium ascorbate and sodium nicotinate were dissolved, so that the mass ratio to the membrane was 0.5% ascorbate. A film was obtained in the same manner as in Example 1A except that sodium and 0.2% sodium nicotinate were supported. The beauty effect verification was also evaluated by the same method as in Example 1A.

<Example 3C>
In the preparation of the biocompatible membrane of Example 1A, a cosmetic ingredient solution in which sodium ascorbate and sodium nicotinate were dissolved was used, and the mass ratios to the membrane were 0.8% sodium ascorbate and 0.1% sodium nicotinate. A film was obtained in the same manner as in Example 1A, except that The beauty effect verification was also evaluated by the same method as in Example 1A.

<Example 3D>
In the preparation of the biocompatible membrane of Example 1A, a cosmetic ingredient solution in which sodium ascorbate and sodium nicotinate were dissolved was used, and the mass ratios to the membrane were 0.8% sodium ascorbate and 0.2% sodium nicotinate. A film was obtained in the same manner as in Example 1A, except that The beauty effect verification was also evaluated by the same method as in Example 1A.

<Example 3E>
In the preparation of the biocompatible membrane of Example 1A, a cosmetic ingredient solution in which sodium ascorbate and sodium nicotinate were dissolved was used, and the mass ratios to the membrane were 0.8% sodium ascorbate and 4.6% sodium nicotinate. A film was obtained in the same manner as in Example 1A, except that The beauty effect verification was also evaluated by the same method as in Example 1A.

<Example 3F>
In the preparation of the biocompatible membrane of Example 1A, a cosmetic ingredient solution in which sodium ascorbate and sodium nicotinate were dissolved was used, and the mass ratios to the membrane were 4.6% sodium ascorbate and 0.2% sodium nicotinate. A film was obtained in the same manner as in Example 1A, except that The beauty 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 carrying only sodium ascorbate or sodium nicotinate was used.

<Comparative Example 3A>
In the preparation of the biocompatible membrane of Example 1A, the same as in Example 1A except that a cosmetic ingredient solution in which sodium nicotinate was dissolved was used to support 0.1% sodium nicotinate as a mass ratio to the membrane. I got a film. The beauty effect verification was also evaluated by the same method as in Example 1A.

<Comparative Example 3B>
In the preparation of the biocompatible membrane of Example 1A, the same as in Example 1A except that 4.6% sodium nicotinate was supported as a mass ratio to the membrane by using a cosmetic ingredient solution in which sodium nicotinate was dissolved. I got a film. The beauty effect verification was also evaluated by the same method as in Example 1A.

<Comparative Example 3C>
In the preparation of the biocompatible membrane of Example 1A, the same as in Example 1A except that 0.5% sodium ascorbate was supported as a mass ratio to the membrane by using a cosmetic ingredient solution in which sodium ascorbate was dissolved. I got a film. The beauty effect verification was also evaluated by the same method as in Example 1A.

<Comparative example 3D>
In the preparation of the biocompatible membrane of Example 1A, the same as in Example 1A except that 0.8% sodium ascorbate was supported as a mass ratio to the membrane by using a cosmetic ingredient solution in which sodium ascorbate was dissolved. I got a film. The beauty effect verification was also evaluated by the same method as in Example 1A.

<Discussion of Example 3>
Table 6 shows the permeation amount [μmol / day] of sodium ascorbate after 1 day of Examples 1A, 3A to 3F and Comparative Examples 1A, 1B, 1D and 3A to 3D, and the cultured skin during the two-week culture period. The amount of melanin produced in 1 [μg / well] was shown. It was confirmed that the cell viability was 90% or more in both Examples and Comparative Examples.

From Table 6, when a biocompatible membrane carrying 0.5% or more sodium ascorbate and 0.1% or more sodium nicotinate and PBS were used, the permeation amount of the second cyclic compound increased and melanin was produced. The amount was significantly reduced.

<Example 4>
Based on Example 1A, the amount of melanin produced was examined by using a 10% glycerol mass ratio, 5% propanediol mass ratio, and 85% mass ratio PBS solution instead of PBS in the beauty effect verification.

<Example 4A>
In the preparation of the biocompatible membrane of Example 1A, a biocompatible membrane was obtained in the same manner as in Example 1A. In the cosmetological effect verification, the cosmetological effect was verified according to Example 1A, except that PBS to which mass ratio 10% glycerol and mass ratio 5% propanediol were added was used instead of PBS alone.

<Discussion of Example 4>
Table 7 shows the permeation amount [μmol / day] of sodium ascorbate in the cultured skin one day after Example 1A, 4A and Comparative Example 1A, and the amount of melanin produced in the cultured skin during the two-week culture period [μg / day]. Well] was shown. It was confirmed that the cell viability was 90% or more in both Examples and Comparative Examples.

According to Table 7, comparing Example 4A with Example 1A and Comparative Example 1A, the amount of melanin produced was higher than that of PBS by using a PBS solution containing 10% glycerol and 5% propanediol rather than PBS alone. It turns out that it can be suppressed.

<Example 5>
Example 5 is composed of Examples 5A to 5F. In Example 5, a biocompatible membrane in which only sodium ascorbate was supported in the membrane was prepared, and PBS to which sodium nicotinate was added instead of PBS was used in the verification of the cosmetic effect.

<Example 5A>
In the preparation of the biocompatible membrane of Example 1A, a biocompatible membrane was obtained in the same manner as in Comparative Example 3C. In the verification of the cosmetological effect, the evaluation was carried out in the same manner as in Example 1A except that PBS supplemented with sodium nicotinate having a mass ratio of 0.10% to the biocompatible membrane was used instead of PBS.

<Example 5B>
In the preparation of the biocompatible membrane of Example 1A, a biocompatible membrane was obtained in the same manner as in Comparative Example 3C. In the verification of the cosmetological effect, the evaluation was carried out in the same manner as in Example 1A except that PBS supplemented with sodium nicotinate having a mass ratio of 0.20% to the biocompatible membrane was used instead of PBS.

<Example 5C>
In the preparation of the biocompatible membrane of Example 1A, a biocompatible membrane was obtained in the same manner as in Comparative Example 3D. In the verification of the cosmetological effect, the evaluation was carried out in the same manner as in Example 1A except that PBS supplemented with sodium nicotinate having a mass ratio of 0.10% to the biocompatible membrane was used instead of PBS.

<Example 5D>
In the preparation of the biocompatible membrane of Example 1A, a biocompatible membrane was obtained in the same manner as in Comparative Example 3D. In the verification of the cosmetological effect, the evaluation was carried out in the same manner as in Example 1A except that PBS supplemented with sodium nicotinate having a mass ratio of 0.20% to the biocompatible membrane was used instead of PBS.

<Example 5E>
In the preparation of the biocompatible membrane of Example 1A, a biocompatible membrane was obtained in the same manner as in Comparative Example 3D. In the verification of the cosmetological effect, the evaluation was performed in the same manner as in Example 1A except that PBS to which sodium nicotinate having a mass ratio of 5.0% with respect to the biocompatible membrane was added was used instead of PBS.

<Example 5F>
In the preparation of the biocompatible membrane of Example 1A, a biocompatible membrane was obtained in the same manner as in Comparative Example 1B. In the verification of the cosmetological effect, the evaluation was carried out in the same manner as in Example 1A except that PBS supplemented with sodium nicotinate having a mass ratio of 0.20% to the biocompatible membrane was used instead of PBS.

<Comparative example 4>
Comparative Example 4 is composed of Comparative Example 4A to Comparative Example 4C. In Comparative Example 4, PBS to which sodium nicotinate was added was used instead of PBS.

<Comparative Example 4A>
In the preparation of the biocompatible membrane of Example 1A, a biocompatible membrane was obtained in the same manner as in Comparative Example 1A. In the verification of the cosmetological effect, the evaluation was carried out in the same manner as in Example 1A except that PBS supplemented with sodium nicotinate having a mass ratio of 0.10% to the biocompatible membrane was used instead of PBS.

<Comparative Example 4B>
In the preparation of the biocompatible membrane of Example 1A, a biocompatible membrane was obtained in the same manner as in Comparative Example 1A. In the verification of the cosmetological effect, the evaluation was carried out in the same manner as in Example 1A except that PBS supplemented with sodium nicotinate having a mass ratio of 0.20% to the biocompatible membrane was used instead of PBS.

<Comparative Example 4C>
In the preparation of the biocompatible membrane of Example 1A, a biocompatible membrane was obtained in the same manner as in Comparative Example 1A. In the verification of the cosmetological effect, the evaluation was performed in the same manner as in Example 1A except that PBS to which sodium nicotinate having a mass ratio of 5.0% with respect to the biocompatible membrane was added was used instead of PBS.

<Discussion of Example 5>
Table 8 shows the permeation amount [μmol / day] of sodium ascorbate after 1 day of Examples 5A to 5F and Comparative Examples 1A, 1B, 3C, 3D and 4A to 4C, and the cultured skin during the two-week culture period. The amount of melanin produced in 1 [μg / well] was shown. It was confirmed that the cell viability was 90% or more in both Examples and Comparative Examples.

According to Table 8, when a membrane carrying 0.5% or more sodium ascorbate and PBS containing 0.10% or more sodium nicotinate were used, the second cyclic compound (beauty agent) was used. The amount of permeation of sodium was increased, and the amount of melanin produced was significantly reduced.

<Example 6>
Example 6 is composed of Examples 6A to 6C. In Example 6, a biocompatible membrane in which only sodium ascorbate was supported in the membrane was prepared, and PBS to which nicotinic acid was added instead of PBS was used in the verification of the cosmetic effect.

<Example 6A>
In the preparation of the biocompatible membrane of Example 1A, a biocompatible membrane was obtained in the same manner as in Comparative Example 3D. In the verification of the cosmetological effect, the evaluation was carried out in the same manner as in Example 1A except that PBS to which 0.20% by mass ratio of nicotinic acid was added to the biocompatible membrane was used instead of PBS.

<Example 6B>
In the preparation of the biocompatible membrane of Example 1A, a biocompatible membrane was obtained in the same manner as in Comparative Example 1B. In the verification of the cosmetological effect, the evaluation was carried out in the same manner as in Example 1A except that PBS to which 0.20% by mass ratio of nicotinic acid was added to the biocompatible membrane was used instead of PBS.

<Example 6C>
In the preparation of the biocompatible membrane of Example 1A, a biocompatible membrane was obtained in the same manner as in Comparative Example 1B. In the verification of the cosmetological effect, the evaluation was carried out in the same manner as in Example 1A except that PBS to which 2.0% nicotinic acid by mass ratio to the biocompatible membrane was added was used instead of PBS.

<Comparative example 5>
Comparative Example 5 is composed of Comparative Example 5A to Comparative Example 5B. In Comparative Example 5, PBS to which nicotinic acid was added was used instead of PBS in the biocompatible membrane and the verification of the cosmetic effect.

<Comparative Example 5A>
In the preparation of the biocompatible membrane of Example 1A, a biocompatible membrane was obtained in the same manner as in Comparative Example 1A. In the verification of the cosmetological effect, the evaluation was carried out in the same manner as in Example 1A except that PBS to which 0.20% by mass ratio of nicotinic acid was added to the biocompatible membrane was used instead of PBS.

<Comparative Example 5B>
In the preparation of the biocompatible membrane of Example 1A, a biocompatible membrane was obtained in the same manner as in Comparative Example 1A. In the verification of the cosmetological effect, the evaluation was carried out in the same manner as in Example 1A except that PBS to which 2.0% nicotinic acid by mass ratio to the biocompatible membrane was added was used instead of PBS.

<Discussion of Example 6>
Table 9 shows the permeation amount [μmol / day] of sodium ascorbate after 1 day of Examples 6A to 6C and Comparative Examples 1A, 1B, 3D, 5A, and 5B, and the amount produced in the cultured skin during the two-week culture period. The amount of melanin produced [μg / well] was shown. It was confirmed that the cell viability was 90% or more in both Examples and Comparative Examples.

According to Table 9, when a membrane supporting 0.8% or more of sodium ascorbate and PBS containing 0.20% or more of nicotinic acid were used, the second cyclic compound (cosmetological agent) was used. The amount of permeation was improved and the amount of melanin produced was significantly reduced.

<Example 7>
Example 7 is composed of Example 7A. In Example 7, a biocompatible membrane in which only sodium ascorbate was supported in the membrane was prepared, and PBS to which gallic acid was added was used instead of PBS in the verification of the cosmetic effect.

<Example 7A>
In the preparation of the biocompatible membrane of Example 1A, a biocompatible membrane was obtained in the same manner as in Comparative Example 1B. In the verification of the cosmetological effect, the evaluation was performed in the same manner as in Example 1A except that PBS to which gallic acid having a mass ratio of 0.20% with respect to the biocompatible membrane was added was used instead of PBS.

<Comparative Example 6>
Comparative Example 6 is composed of Comparative Example 6A. In Comparative Example 6, a biocompatible membrane was prepared, and PBS to which gallic acid was added was used instead of PBS in the verification of the cosmetological effect.

<Comparative Example 6A>
In the preparation of the biocompatible membrane of Example 1A, a biocompatible membrane was obtained in the same manner as in Comparative Example 1A. In the verification of the cosmetological effect, the evaluation was performed in the same manner as in Example 1A except that PBS to which gallic acid having a mass ratio of 0.20% with respect to the biocompatible membrane was added was used instead of PBS.

<Discussion of Example 7>
Table 10 shows the permeation amount [μmol / day] of sodium ascorbate in the cultured skin one day after Example 7A and Comparative Examples 1B and 6A, and the amount of melanin produced in the cultured skin during the two-week culture period [μg / day]. Well] was shown. It was confirmed that the cell viability was 90% or more in both Examples and Comparative Examples.

According to Table 10, when a membrane carrying 2.7% sodium ascorbate and PBS containing 0.20% gallic acid were used, the permeation amount of the second cyclic compound was improved and melanin was observed. The output was significantly reduced.

<Example 8>
Example 8 is composed of Example 8A. In Example 8, a biocompatible membrane in which only sodium ascorbate was supported in the membrane was prepared, and PBS to which menthol was added instead of PBS was used in the verification of the cosmetic effect.

<Example 8A>
In the preparation of the biocompatible membrane of Example 1A, a biocompatible membrane was obtained in the same manner as in Comparative Example 1B. In the verification of the cosmetological effect, the evaluation was performed in the same manner as in Example 1A except that PBS to which menthol having a mass ratio of 0.20% with respect to the biocompatible membrane was added was used instead of PBS.

<Comparative Example 7>
Comparative Example 7 is composed of Comparative Example 7A. In Comparative Example 7, a biocompatible film was prepared, and a solution containing menthol instead of PBS was used in the verification of the cosmetic effect.

<Comparative Example 7A>
In the preparation of the biocompatible membrane of Example 1A, a biocompatible membrane was obtained in the same manner as in Comparative Example 1A. In the verification of the cosmetological effect, the evaluation was carried out in the same manner as in Example 1A except that a solution containing 0.20% menthol by mass with respect to the biocompatible membrane was used instead of PBS.

<Discussion of Example 8>
Table 11 shows the permeation amount [μmol / day] of sodium ascorbate in the cultured skin one day after Example 8A and Comparative Examples 1B and 7A, and the amount of melanin produced in the cultured skin during the two-week culture period [μg / day]. Well] was shown. It was confirmed that the cell viability was 90% or more in both Examples and Comparative Examples.

According to Table 11, when a membrane supporting 2.7% sodium ascorbate and a solution containing 0.20% menthol were used, the permeation amount of the second cyclic compound was improved and melanin was produced. The amount was significantly reduced.

<Example 9>
Example 9 is composed of Example 9A. In Example 9, a biocompatible membrane in which only gallic acid was supported in the membrane was prepared, and PBS to which sodium ascorbate was added instead of PBS was used in the verification of the cosmetic effect.

<Example 9A>
In the preparation of the biocompatible membrane of Example 1A, a biocompatible membrane was obtained in the same manner as in Comparative Example 1G. In the verification of the cosmetological effect, the evaluation was carried out in the same manner as in Example 1A except that PBS to which sodium ascorbate having a mass ratio of 3.0% with respect to the biocompatible membrane was added was used instead of PBS.

<Comparative Example 8>
Comparative Example 8 is composed of Comparative Example 8A. In Comparative Example 8, a biocompatible membrane was prepared, and PBS to which sodium ascorbate was added was used instead of PBS in the verification of the cosmetic effect.

<Comparative Example 8A>
In the preparation of the biocompatible membrane of Example 1A, a biocompatible membrane was obtained in the same manner as in Comparative Example 1A. In the verification of the cosmetological effect, the evaluation was carried out in the same manner as in Example 1A except that PBS to which sodium ascorbate having a mass ratio of 3.0% with respect to the biocompatible membrane was added was used instead of PBS.

<Discussion of Example 9>
Table 12 shows the permeation amount [μmol / day] of sodium ascorbate in the cultured skin one day after Example 9A and Comparative Examples 1G and 8A, and the amount of melanin produced in the cultured skin during the two-week culture period [μg / day]. Well] was shown. It was confirmed that the cell viability was 90% or more in both Examples and Comparative Examples.

According to Table 12, when a membrane carrying 0.2% gallic acid and PBS supplemented with 3.0% sodium ascorbate were used, the permeation amount of the second cyclic compound was improved and melanin was observed. The output was significantly reduced.

<Example 10>
Example 10 is composed of Example 10A. In Example 10, a biocompatible membrane in which only menthol was supported in the membrane was prepared, and PBS to which sodium ascorbate was added instead of PBS was used in the verification of the cosmetic effect.

<Example 10A>
In the preparation of the biocompatible membrane of Example 1A, a biocompatible membrane was obtained in the same manner as in Comparative Example 1J. In the verification of the cosmetological effect, the evaluation was carried out in the same manner as in Example 1A except that PBS to which sodium ascorbate having a mass ratio of 3.0% with respect to the biocompatible membrane was added was used instead of PBS.

<Discussion of Example 10>
Table 13 shows the permeation amount [μmol / day] of sodium ascorbate in the cultured skin one day after Example 10A and Comparative Examples 1J and 8A, and the amount of melanin produced in the cultured skin during the two-week culture period [μg / day]. Well] was shown. It was confirmed that the cell viability was 90% or more in both Examples and Comparative Examples.

According to Table 13, when a membrane carrying 0.2% menthol and PBS supplemented with 3.0% sodium ascorbate were used, the permeation amount of the second cyclic compound was improved and melanin was produced. The amount was significantly reduced.

<Example 11>
Example 11 is composed of Example 11A. In Example 11, a biocompatible membrane in which arbutin and gallic acid were supported in the membrane was prepared, and PBS was used in the verification of the cosmetic effect.

<Example 11A>
In the preparation of the biocompatible membrane of Example 1A, arbutin was used instead of sodium ascorbate, and 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, respectively. A biocompatible film was obtained in the same manner as in Example 1A except that the content was set to 2%. In the beauty effect verification, it was evaluated by the same method as in Example 1A.

<Comparative Example 9>
Comparative Example 9 is composed of Comparative Example 9A. In Comparative Example 9, a biocompatible membrane in which arbutin was supported in the membrane was prepared, and PBS was used in the verification of the cosmetic effect.

<Comparative Example 9A>
In the preparation of the biocompatible membrane of Example 1A, arbutin was used instead of sodium ascorbate so that the mass ratio of arbutin in the membrane to the membrane was 2.3%, but the living body was the same as in Example 1A. A compatible membrane was obtained. In the beauty effect verification, it was evaluated by the same method as in Example 1A.

<Discussion of Example 11>
Table 14 shows the permeation amount [μmol / day] of arbutin in the cultured skin 1 day after Example 11A and Comparative Examples 9A and 1G, and the amount of melanin produced in the cultured skin during the two-week culture period [μg / well]. showed that. It was confirmed that the cell viability was 90% or more in both Examples and Comparative Examples.

According to Table 14, when a membrane carrying 2.3% arbutin and 0.2% gallic acid and PBS were used, the permeation amount of the second cyclic compound was improved and the melanin production was significantly reduced. I let you.

<Example 12>
Example 12 is composed of Example 12A. In Example 12, a biocompatible membrane in which ellagic acid and gallic acid were supported in the membrane was prepared, and PBS was used in the verification of the cosmetic effect.

<Example 12A>
In the preparation of the biocompatible membrane of Example 1A, ellagic acid was used instead of sodium ascorbate, and gallic acid was used instead of sodium nicotinate, and the mass ratios of ellagic acid and gallic acid in the membrane to the membrane were 0.5, respectively. A biocompatible membrane was obtained in the same manner as in Example 1A except that the content was set to 0.2%. In the beauty effect verification, it was evaluated by the same method as in Example 1A.

<Comparative Example 10>
Comparative Example 10 is composed of Comparative Example 10A. In Comparative Example 10, a biocompatible membrane in which ellagic acid was supported in the membrane was prepared, and PBS was used in the verification of the cosmetic effect.

<Comparative Example 10A>
In the preparation of the biocompatible membrane of Example 1A, 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%, which was the same as that of Example 1A. To obtain a biocompatible membrane. In the beauty effect verification, it was evaluated by the same method as in Example 1A.

<Discussion of Example 12>
Table 15 shows the permeation amount [μmol / day] of ellagic acid in the cultured skin after 1 day of Examples 12A and 10A and 1G, and the amount of melanin produced in the cultured skin during the two-week culture period [μg / well]. ]showed that. It was confirmed that the cell viability was 90% or more in both Examples and Comparative Examples.

According to Table 15, when a membrane carrying 0.5% ellagic acid and 0.2% gallic acid and PBS were used, the permeation amount of the second cyclic compound was improved and the amount of melanin produced was significantly increased. Reduced.

<Example 13>
Example 13 is composed of Example 13A. In Example 13, a biocompatible membrane in which sodium ascorbate and silingaic acid were supported in the membrane was prepared, and PBS was used in the verification of the cosmetic effect.

<Example 13A>
In the preparation of the biocompatible membrane of Example 1A, silingic acid was used instead of sodium nicotinate, the target thickness was set to 2700 nm, and the mass ratios of ascorbic acid and silingic acid in the membrane to the membrane were 9.8 and 0, respectively. A biocompatible membrane was obtained in the same manner except that it was supported by 9%. In the cosmetological effect verification, evaluation was performed by the same method as in Example 1A except that PBS was used.

<Discussion of Example 13>
Table 16 shows the permeation amount [μmol / day] of sodium ascorbate in the cultured skin one day after Example 13A and Comparative Example 1A, and the amount of melanin produced in the cultured skin during the two-week culture period [μg / well]. showed that. It was confirmed that the cell viability was 90% or more in both Examples and Comparative Examples.

According to Table 16, when PBS supporting a membrane carrying 9.8% sodium ascorbate and 0.9% silingaic acid was used, the permeation amount of the second cyclic compound was improved and the amount of melanin produced was increased. It was significantly reduced.

The cosmetics or medical materials of the present disclosure can be suitably used in various fields such as a beauty field and a pharmaceutical field.

Claims (17)

The first cyclic compound represented by the following formula (1) or a salt thereof, and

(In formula (1), X is CH, N, CH ₂ or NH, the adjacent atoms 1 to 6 are saturated or unsaturated, and R ₁ is at least one of a carboxyl group and a hydroxyl group. R ₂ is at least one selected from the group consisting of propenoic acid group, isopropyl group, methoxy group, aldehyde group, methyl group, hydroxymethyl group and hydrogen, and m is an integer of 1 or more. n is an integer greater than or equal to 0, and the sum of m and n is 10 or less)
A second cyclic compound as an active ingredient or a salt thereof,
Cosmetics or medical materials with biocompatible membranes. The cosmetic or medical material according to claim 1, wherein the biocompatible membrane is self-supporting and can hold at least one of the first cyclic compound and the second cyclic compound. The cosmetic or medical material according to claim 1 or 2, wherein the biocompatible film contains regenerated cellulose as a main component. 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. The cosmetic or medical material according to any one of claims 1 to 4, wherein the first cyclic compound or a salt thereof has a partition coefficient larger than that of the second cyclic compound or a salt thereof. The cosmetic or medical material according to any one of claims 1 to 5, wherein the first cyclic compound or a salt thereof has a partition coefficient of 0 or more and 4.0 or less. The cosmetic or medical material according to any one of claims 1 to 6, wherein the first cyclic compound or a salt thereof has a molecular weight of 94 or more and 500 or less. The first cyclic compound or a salt thereof is nicotinic acid, nicotinate, vanillic acid, vanillic acid, ferulic acid, ferulate, pyridoxal, pyridoxal hydrochloride, gallic acid, gallic acid, syringaic acid and menthol. The cosmetic or medical material according to any one of claims 1 to 7, which comprises at least one selected from the group consisting of. The cosmetic or medical material according to any one of claims 1 to 8, wherein the second cyclic compound or a salt thereof contains at least one of a hydroxyl group and a carboxyl group. The cosmetic according to any one of claims 1 to 9, wherein the second cyclic compound or a salt thereof contains at least one selected from the group consisting of ascorbic acid, sodium ascorbic acid, arbutin, and ellagic acid. Or medical material. From claim 1, the ratio of the mass of the first cyclic compound or its salt to the total mass of the biocompatible membrane carrying the first cyclic compound or its salt is 0.1 or more and 50 or less. The cosmetic or medical material according to any one of 10. From claim 1, the ratio of the mass of the second cyclic compound or its salt to the total mass of the biocompatible membrane carrying the second cyclic compound or its salt is 0.5 or more and 50 or less. The cosmetic or medical material according to any one of 10. The invention according to any one of claims 1 to 11, wherein at least one of the first cyclic compound or a salt thereof and the second cyclic compound or a salt thereof is carried in the biocompatible membrane. Cosmetics or medical materials. The cosmetic or medical material according to any one of claims 1 to 13, further comprising an aqueous solution containing water and one or more polyhydric alcohols. The cosmetic or medical material according to claim 14, wherein the one or more polyhydric alcohols are glycerol and / or propanediol. 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 glycerol and 5% by mass or more and 15% by mass or less of the propanediol. The method for using a cosmetic or medical material in which the biocompatible film is brought into contact with the skin in the cosmetic or medical material according to any one of claims 1 to 16.