Classifications

• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
  • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
  • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
  • A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
  • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
  • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
  • A61K47/12—Carboxylic acids; Salts or anhydrides thereof
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
  • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
  • A61K47/22—Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K8/00—Cosmetics or similar toiletry preparations
  • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
  • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
  • A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
  • A61K8/34—Alcohols
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K8/00—Cosmetics or similar toiletry preparations
  • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
  • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
  • A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
  • A61K8/36—Carboxylic acids; Salts or anhydrides thereof
  • A61K8/368—Carboxylic acids; Salts or anhydrides thereof with carboxyl groups directly bound to carbon atoms of aromatic rings
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K8/00—Cosmetics or similar toiletry preparations
  • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
  • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
  • A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K8/00—Cosmetics or similar toiletry preparations
  • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
  • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
  • A61K8/60—Sugars; Derivatives thereof
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K8/00—Cosmetics or similar toiletry preparations
  • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
  • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
  • A61K8/67—Vitamins
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K8/00—Cosmetics or similar toiletry preparations
  • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
  • A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
  • A61K8/73—Polysaccharides
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K9/00—Medicinal preparations characterised by special physical form
  • A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
  • A61Q19/00—Preparations for care of the skin

Definitions

• This disclosure relates to cosmetics or medical materials.
• an active ingredient is absorbed from a living body, for example, skin, that is, a cosmetic effect, a disease treatment or a preventive effect is generated by transdermal absorption.
• ascorbic acid has the function of suppressing the production of wrinkle-related collagen and the production of tannins and sunburns and melanin, as well as reducing melanin, so that ascorbic acid penetrates into the lower layer of the skin epidermis where melanin is produced. If done, it will be effective in preventing and treating sunburn.
• Patent Documents 1 to 3 disclose a composition for external use containing a substance having a cosmetic effect such as ascorbic acid and an accelerator that promotes absorption of skin such as ascorbic acid.
• the present disclosure provides a cosmetic or medical material capable of efficiently transdermally absorbing an active ingredient in the cosmetic field, pharmaceutical field, and the like.
• 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 Between the adjacent atoms is a saturated or unsaturated bond, R 1 is at least one of a carboxyl group and a hydroxyl group, and R 2 is a propenoic acid group, isopropyl group, methoxy group, aldehyde group, methyl group And at least one selected from the group consisting of a hydroxymethyl group and hydrogen, 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), A second cyclic compound or a salt thereof as an active ingredient and a biocompatible membrane are provided.
• formula (1) X is CH, N, CH 2 or NH, and 1 to 6 Between the adjacent atoms is a saturated or unsaturated bond, R 1 is at least one of a carboxyl group and
• a cosmetic or a medical material capable of efficiently transdermally absorbing an active ingredient in the cosmetic field, the pharmaceutical field, or the like can be obtained.
• the inventor of the present application has examined in detail the combination of an active ingredient in the cosmetic field, pharmaceutical field and the like that can efficiently perform transdermal absorption and an accelerator for transdermal absorption.
• both the active ingredient and the accelerator are cyclic compounds
• the transdermal absorbability is improved by the addition of the accelerator by causing interactions such as charge transfer and hydrogen bonding between the cyclic compounds. It was found that the effect can be increased efficiently.
• An outline of the cosmetic or medical material of the present disclosure is as follows.
• the cosmetic or medical material of the present disclosure includes a 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, 1 to 6 adjacent atoms are a saturated bond or an unsaturated bond, 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, 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)
• composition of cosmetics or medical materials includes a transdermal absorption enhancer, an active ingredient, and a biocompatible film.
• an active ingredient of a cosmetic it may be called a cosmetic
• an active ingredient of a pharmaceutical it may be called a medical material.
• the cosmetics or medical materials of the present disclosure include quasi-drugs classified between cosmetics and pharmaceuticals.
• the transdermal absorption enhancer means an agent that increases the amount of penetration of desired components into the skin.
• the transdermal absorption enhancer of the present application is a cyclic compound represented by the formula (1).
• the cyclic compound that is a transdermal absorption enhancer is referred to as a first cyclic compound.
• a compound which is an active ingredient in the cosmetic field, pharmaceutical field and the like targeted by the present application is also a cyclic compound (hereinafter referred to as a second cyclic compound). Therefore, 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 can easily penetrate into the skin. It is possible to enhance the percutaneous absorption promoting effect of the second cyclic compound.
• At least one of the first cyclic compound and the second cyclic compound is an aromatic compound, and more desirably, both the first cyclic compound and the second cyclic compound are aromatic compounds. is there.
• an interaction derived from an aromatic ring can be used, and the first cyclic compound and the second cyclic compound can be used. The interaction between the cyclic compound and the second cyclic compound is more likely to occur, and both the first cyclic compound and the second cyclic compound are likely to penetrate into the skin.
• At least one of the first cyclic compound and the second cyclic compound includes a hydroxyl group, a carboxyl group, or both.
• a hydroxyl group and a carboxyl group it becomes possible to use 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 easy to penetrate into the skin.
• the first cyclic compound is a cyclic compound represented by the following formula (1) or a salt thereof.
• X is CH, N, CH 2 or NH
• the adjacent atoms of 1 to 6 are a saturated bond or an unsaturated bond
• 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
• m is an integer of 1 or more
• n Is an integer of 0 or more
• the sum of m and n is 10 or less.
• m is 2 or more, that is, when the R 1 there are two or more, R 1 is each independently a carboxyl group or a hydroxyl group.
• n is 2 or more, that is, when R 2 is present two or more, R 2 are each independently propene group, an isopropyl group, a methoxy group, an aldehyde group, a methyl group , A hydroxymethyl group or hydrogen.
• the salt of the first cyclic compound is a salt of an anion having a proton removed from the carboxyl group or hydroxyl group of the first cyclic compound and any monovalent or polyvalent cation, or X is NH. Contains the hydrochloride salt in some cases.
• the first cyclic compound represented by the formula (1) or a salt thereof includes, for example, nicotinic acid, sodium nicotinate, vanillic acid, sodium vanillate, gallic acid, ferulic acid, sodium ferulate, pyridoxal, pyridoxal hydrochloride, Menthol, pyromellitic acid, mellitic acid, trimellitic acid, hydroxybenzoic acid, dihydroxybenzoic acid, hydroxyisophthalic acid, isovanillic acid, syringic acid, anisic acid, methoxysalicylic acid, trimethoxybenzoic acid, phloroglucinol, methoxycatechol, resorcinol, It is at least one selected from the group consisting of pyrogallol, methoxyhydroquinone, syringic acid, methyl pyrogallol, and vanillin.
• Cosmetics or medical materials may contain only one kind of the aforementioned first cyclic compound as a transdermal absorption enhancer, or may contain two or more kinds.
• the molecular weight of the first cyclic compound or a salt thereof is desirably 94 or more and 500 or less. When the molecular weight is 500 or less, the size of the molecule or ion of the first cyclic compound becomes small, and the first cyclic compound easily penetrates into the skin.
• the first cyclic compound or a salt thereof desirably has higher hydrophobicity than the second cyclic compound described later. As described above, the first cyclic compound is more hydrophobic than the second cyclic compound, which is the active ingredient, so that the complex due to the interaction between the first cyclic compound and the second cyclic compound.
• the body has a higher hydrophobicity than the second cyclic compound and the permeability to the skin is increased.
• the hydrophobicity of the first cyclic compound can be evaluated by, for example, a partition coefficient.
• the higher the partition coefficient P the higher the hydrophobicity (or fat solubility) of the compound.
• the partition coefficient takes a negative value.
• the partition coefficient of the first cyclic compound is desirably 0 or more. More desirably, it is 0 or more and 4.0 or less. If the partition coefficient is 0 or more, the first cyclic compound can penetrate into the skin, and when it forms a complex with the second cyclic compound, the second cyclic compound as an active ingredient is It can be absorbed into the skin more than when used alone. If the distribution coefficient is greater than 4.0, the hydrophobicity of the first cyclic compound may be too high, making it difficult to penetrate into the skin.
• the active ingredient which this application makes object is the 2nd cyclic compound or its salt.
• the interaction is likely to occur, and both the first cyclic compound and the second cyclic compound are in the skin. It is thought that it becomes easy to penetrate into.
• the second cyclic compound is also an aromatic compound.
• the second cyclic compound preferably contains a hydroxyl group, a carboxyl group, or both.
• the salt of the second cyclic compound includes a salt of an anion in which a proton is eliminated from the carboxyl group or hydroxyl group of the second cyclic compound and any monovalent or polyvalent cation.
• the second cyclic compound may have whitening, anti-wrinkle, UV cut, moisturizing effect and the like.
• Beauty ingredients satisfying such conditions include, for example, vitamin A such as retinol, retinal, retinoic acid, vitamin B such as thiamine, riboflavin, pyridoxine, pyridoxamine, folic acid, vitamin D such as ergocalciferol, cholecalciferol, ⁇ -Vitamin E such as tocopherol, vitamins such as phylloquinone, menaquinone vitamin K, vitamin A derivatives such as tretinoin, retinol palmitate, glyceryl ascorbic acid, L-ascorbic acid-2-magnesium phosphate, ascorbic acid glucoside, etc.
• Vitamin C derivatives such as ⁇ -tocopherol acetate, ⁇ -tocopheryl quinone, tocopheryl phosphate, tranexamic acid, arbutin, hydroquinone, kojic acid, potassium 4-methoxysalicylate Lucinol, ellagic acid and gossypetin, myricetin, flavonols of rutin, proline, phenylalanine, there is tryptophan, tyrosine, an amino acid such as histidine.
• a 2nd cyclic compound you may have effects, such as analgesia, vasodilation, angina treatment, asthma treatment, etc., for example.
• Medical components that satisfy such conditions include, for example, acetylsalicylic acid, thiaramide hydrochloride, acetaminophen, hydrocortisone, prednisolone, triamcinolone, dexamethasone, betamethasone, minoxidil, finasteride, cephalanthin, isosorbide mononitrate, isosorbide dinitrate, bisoprolol, estrone, Examples include estradiol and estriol.
• the second cyclic compound is selected from the group consisting of ascorbic acid, sodium ascorbate, 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 uses or two or more of different uses. Moreover, the salt of these 2nd cyclic compounds, hydrochloride, etc. may be sufficient.
• the molecular weight of the second cyclic compound or a salt thereof is desirably 4000 or less.
• the molecular weight of the second cyclic compound or a salt thereof is more desirably 500 or less.
• 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 likely to penetrate into the skin.
• the first cyclic compound has higher hydrophobicity than the second cyclic compound or a salt thereof.
• the hydrophobicity of the complex of the first cyclic compound and the second cyclic compound is reduced to the second cyclic compound. It increases compared to a simple substance, and the second cyclic compound is easily absorbed percutaneously.
• the second cyclic compound when the distribution coefficient of the second cyclic compound is less than 0, the second cyclic compound alone is difficult to absorb percutaneously.
• the percutaneous absorption promoting effect of the first cyclic compound works more effectively, and the absorption to the skin can be enhanced.
• the second cyclic compound having a partition 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 include ascorbic acid, tocopheryl phosphate, arbutin, kojic acid, proline, phenylalanine, tryptophan, tyrosine, histidine, rutin, and isosorbide mononitrate.
• Ascorbic acid is known to be effective for, for example, spots and wrinkles.
• 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.
• ascorbic acid is used as the second cyclic compound of the cosmetic or medical material of the present disclosure, as will be described in the following examples, when the first cyclic compound is used, absorption into the skin is used alone Increased compared to
• Biocompatible membrane can hold at least one of the first cyclic compound or a salt thereof and the second cyclic compound or a salt thereof. Since the biocompatible membrane is brought into contact with or attached to the skin or the like, it is desirable to have biocompatibility.
• the biocompatibility means that redness, irritation, or the like hardly occurs in a living body such as skin due to its use, or that these hardly occur in many subjects.
• the biocompatible membrane includes a first cyclic compound or a salt thereof in a solid state, a state dissolved in an appropriate liquid, or a state dispersed in a gel, and a second cyclic compound or a salt thereof. It is possible to retain at least one of the salt. Thereby, it is possible to stably maintain at least one of the first cyclic compound and the second cyclic compound in contact with a living body, for example, skin.
• the biocompatible membrane can be self-supporting.
• Self-supporting means that the membrane can be maintained without any other support. For example, when a part of the biocompatible membrane is picked up by using fingers, tweezers, etc., the membrane breaks. 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, dextran, dextrin, gluten, lignin, pectin, pullulan, xanthan gum, xylan, poly Materials that are safe for living bodies such as lactic acid, cellulose, and cellulose derivatives such as hydroxyethyl cellulose, hydroxypropyl cellulose, carboxymethyl cellulose, methyl cellulose, and ethyl cellulose are preferable. A more preferred material is regenerated cellulose.
• Regenerated cellulose has the characteristic of not having the type I crystal characteristic of natural cellulose, so that it can easily retain moisture moderately and can have an excellent humidity control function. Accordingly, when the regenerated cellulose is attached to a living body, it does not easily cause stuffiness or rash while retaining appropriate moisture. Furthermore, it can be expected that the ability to carry the first and second cyclic compounds is enhanced by controlling the structure of the regenerated cellulose such as the pore and density.
• the raw material cellulose used for producing the biocompatible membrane is not particularly limited.
• 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.
• it is beneficial that the impurity concentration of the raw material cellulose is 10 wt% or less.
• the biocompatible membrane has a thickness of 3 ⁇ m or less. If the thickness of the biocompatible membrane is 3 ⁇ m or less, there is little discomfort when placed on the skin, and wearability can be improved.
• the thickness of the biocompatible membrane is more preferably 20 nm or more and 1300 nm or less. When the thickness is 1300 nm or less, the biocompatible film can be attached to the skin without using an adhesive or a pressure-sensitive adhesive, or an adhesive layer or a pressure-sensitive adhesive layer. As a result, stuffiness and the like can be reduced without burdening the living body, and cosmetics or medical materials can be used.
• the biocompatible membrane has a size corresponding to the use of the cosmetic or medical material and the site of the skin to be used.
• the biocompatible membrane can be applied to the skin such as the face and arms.
• Biocompatible membranes according to embodiments of the present disclosure typically have an area of 7 mm 2 or greater. When the area of the biocompatible membrane is 7 mm 2 or more, it is possible to obtain a cosmetic effect by covering a local region of the skin such as a stain. Moreover, if a biocompatible membrane having a larger area is used, it is possible to cover the skin over a wide range.
• the cosmetic or medical material of the present disclosure can be applied to a living body other than the skin. For example, in order to enhance the healing effect of the organ, it can be attached to the surface of the organ.
• the ratio of the mass of the first cyclic compound or salt thereof to the total mass of the biocompatible membrane carrying the first cyclic compound or salt thereof is preferably 0.1 to 50 mass ratio. If it is 0.1 mass ratio or more, the effect of promoting percutaneous absorption of the first cyclic compound can be obtained, and the second cyclic compound can effectively penetrate into the skin.
• 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 salt thereof to the total mass of the biocompatible membrane carrying the second cyclic compound or salt thereof is preferably 0.5 or more and 50 mass ratio or less. If it is 0.5 mass ratio or more, the 2nd cyclic compound can be penetrated into skin effectively. 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.
• the cosmetic or medical material may further include a mounting liquid in order to adhere to the skin on which the biocompatible membrane is disposed.
• a liquid that is safe for a living body can be used as the mounting liquid.
• the mounting liquid includes at least one selected from an aqueous solution such as pure water, physiological saline, lotion, and beauty liquid, and a lotion, an emulsion, a cosmetic liquid, and a cream containing an organic solvent.
• the mounting fluid includes water and a polyhydric alcohol.
• polyhydric alcohol examples include glycerol and propanediol, and the mounting solution may contain both glycerol and propanediol. Since polyhydric alcohol is slightly more hydrophobic than water, the mounting liquid containing water and polyhydric alcohol can dissolve both the first cyclic compound and the second cyclic compound. Thereby, the first cyclic compound and the second cyclic compound are uniformly disposed in the biocompatible membrane, the first cyclic compound and the second cyclic compound interact, and the complex is removed from the skin. It is possible to permeate into.
• the concentration of the mounting liquid desirably includes, for example, 5% by mass to 10% by mass of glycerol, 5% by mass to 15% by mass of propanediol, and the remaining water. Since the mounting liquid of this formulation has little irritation to the skin or the like, it is possible to easily mount the biocompatible membrane containing the mounting liquid for a long time.
• compositions of cosmetics or medical materials other than the first cyclic compound and the second cyclic compound may be included.
• ingredients of cosmetics hyaluronic acid, ceramide, collagen, amino acid, elastin, various extracts, citric acid, lecithin, carbomer, xanthan gum, dextran, palmitic acid, lauric acid, petrolatum, titanium oxide, iron oxide, phenoxyethanol, fullerene , Astaxanthin, coenzyme, human oligopeptide, glycerin, diglycerin, sodium lactate, sorbitol, pyrrolidone carboxylic acid, fatty acid polyglyceryl, polyglycerin, jojoba oil, trimethylglycine, mannitol, trehalose, glycosyl trehalose, pullulan, erythritol, elastin, dipropylene Glycol, butylene glycol, ethyl e
• isosorbide nitrate isosorbide nitrate, indomethacin, diflucortron valerate, acyclovir, ketoconazole, ketoprofen, diclofenac sodium, dexamethasone propionate, felbinac, clobetasol propionate, loxoprofen, methyl salicylate, tacrolimus, etc.
• isosorbide nitrate indomethacin, diflucortron valerate, acyclovir
• ketoconazole ketoprofen
• diclofenac sodium dexamethasone propionate
• felbinac clobetasol propionate
• loxoprofen methyl salicylate
• tacrolimus etc.
• the cosmetic or medical material can be configured in various ways.
• the first cyclic compound and the second cyclic compound may be supported on the biocompatible membrane in advance.
• the first cyclic compound and the second cyclic compound can be supported on the biocompatible membrane in a solid state.
• 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 cut.
• ascorbic acid easily changes from a reduced form to an oxidized form in an aqueous solution.
• the biocompatible membrane when the biocompatible membrane is loaded with reduced ascorbic acid as the second cyclic compound in a solid state, it is difficult 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 carried in the biocompatible membrane, or may be carried 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.
• One of the first and second cyclic compounds carried on the biocompatible membrane One of the first cyclic compound and the second cyclic compound may be carried on the biocompatible membrane in advance.
• the other of the first cyclic compound and the second cyclic compound can be obtained by, for example, dissolving the other in the mounting liquid and including the mounting liquid in the biocompatible membrane when using cosmetics or medical materials. Cyclic compounds may be placed on the biocompatible membrane.
• Cyclic compounds may be placed on the biocompatible membrane.
• it is supported on the biocompatible membrane for the purpose of separating and holding one. It does not have to be.
• 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 be arranged on the biocompatible membrane at the time of use without being supported on the biocompatible membrane. 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 disposed on the biocompatible membrane by dropping or the like. Good.
• a first mounting liquid and a second mounting liquid in which the first cyclic compound and the second cyclic compound are respectively dissolved are prepared, and the first mounting liquid and the second mounting liquid are used as a living body at the time of use.
• the first cyclic compound and the second cyclic compound can be arranged on the skin surface more than the case where they are supported on the biocompatible membrane, and the amount of penetration into the skin can be improved. May be possible.
• the cosmetic or medical material of the present disclosure is used in such a manner that the first cyclic compound or a salt thereof and the second cyclic compound or a salt thereof are held on the biocompatible film and the biocompatible film is brought into contact with the skin. To do.
• the first cyclic compound or a salt thereof and the second cyclic compound or a salt thereof may be held on the biocompatible membrane, and the makeup of the present disclosure
• the material or the medical material may be any one of the above embodiments (1) to (3).
• the method of using the cosmetic or medical material according to the present disclosure is classified into the following three types according to the timing at which the mounting liquid is arranged.
• the mounting liquid can be arranged at the following three types of timing.
• (1) When dripping onto the skin First the mounting solution is dropped onto the surface of the skin, and a biocompatible membrane is applied to the skin so as to cover the dropped mounting solution.
• (2) When dropping onto the biocompatible membrane First the mounting solution is included in the biocompatible membrane, and the biocompatible membrane containing the mounting solution is applied to the skin.
• the biocompatible membrane can stably maintain the state in which the skin and the mounting liquid are in contact with each other at any timing. For this reason, the first cyclic compound and the second cyclic compound in the wearing solution can be stably percutaneously absorbed into the skin for a long period of time.
• the first cyclic compound represented by formula (1) or a salt thereof and the second cyclic compound or salt thereof as an active ingredient have a ring structure. Therefore, an interaction is likely to occur between the first cyclic compound and the second cyclic compound, and both the first cyclic compound and the second cyclic compound easily penetrate into the skin.
• the cyclic compound represented by the formula (1) is a substance that has a relatively large partition coefficient and is easily absorbed through the skin. Therefore, even if the second cyclic compound is water-soluble, that is, the second cyclic compound has a small partition coefficient and is hardly percutaneously absorbed, it forms a complex with the first cyclic compound. This facilitates percutaneous absorption, and allows the second cyclic compound to effectively penetrate into the skin.
• the cosmetic or medical material of the present disclosure includes a biocompatible film
• 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 held stably. Since the biocompatible film is hypoallergenic, it is possible to realize a cosmetic or a medical material that can be applied to the skin for a period of time depending on the application.
• 1st cyclic compound and 2nd cyclic compound are commercial items provided with use, purity as required, safety for specimen, etc. Can be used.
• the wearing liquid is pure water, physiological saline, commercially available lotion, aqueous solution such as cosmetic liquid, lotion containing organic solvent, milky lotion, cosmetic liquid, cream, etc. or the first cyclic compound. Or a solution containing beauty and medical ingredients and the above-mentioned polyhydric alcohol in the above-mentioned ratio.
• Biocompatible membrane A biocompatible membrane composed mainly of regenerated cellulose can be produced, for example, by the following method.
• 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.
• a biocompatible membrane having a thickness of 1300 nm (1.3 ⁇ m) or less can be obtained stably.
• cellulose As the cellulose, as long as it has a predetermined weight average molecular weight, cellulose derived from plants such as pulp or cotton, or cellulose produced by organisms such as bacteria can be used. It is useful that the impurity concentration of cellulose as a raw material is 10 wt% or less.
• a solvent containing an ionic liquid may be used.
• a solvent containing at least an ionic liquid cellulose can be dissolved in a relatively short time.
• An ionic liquid is a salt composed of an anion and a cation, and can exhibit a liquid state at a temperature of 150 ° C. or lower.
• an ionic liquid containing an amino acid or an alkyl phosphate ester can be used as the ionic liquid for dissolving cellulose.
• an ionic liquid containing an amino acid or an alkyl phosphate ester can be used.
• cellulose can be dissolved while suppressing a decrease in molecular weight.
• an amino acid is a component present in a living body, it can be said that an ionic liquid containing an amino acid enables the production of a regenerative biocompatible membrane that is safer for the living body.
• an ionic liquid represented by the following general formula (s1) can be used as the ionic liquid for dissolving cellulose.
• the ionic liquid represented by the general formula (s1) is an example in which the anion is an amino acid.
• the anion includes 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.
• R 1 to R 6 independently represent a hydrogen atom or a substituent.
• the substituent may be an alkyl group, a hydroxyalkyl group or a phenyl group, and may contain a branch in the carbon chain.
• the substituent may include an amino group, a hydroxyl group, a carboxyl group, and the like.
• n is an integer of 1 or more and 5 or less.
• the ionic liquid represented by the following general formula (s2) can also be used as an ionic liquid which melt
• 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 on the substrate. Thereafter, the polymer gel sheet on the substrate is immersed in a liquid that does not dissolve cellulose (hereinafter sometimes referred to as “rinse solution”). This step may be said to be a step of washing the polymer gel sheet in which the solvent containing the ionic liquid is removed from the polymer gel sheet.
• 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.
• the solvent and the like are removed from the polymer gel sheet.
• the polymer gel sheet is dried.
• 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 time and temperature sufficient to remove a part or all of the solvent and the rinsing liquid used for dissolving the cellulose solution may be applied.
• a biocompatible membrane can be obtained by removing the solvent from the polymer gel sheet.
• the obtained biocompatible membrane 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 membrane is taken out of the solution and dried. Thereby, a biocompatible membrane carrying at least one of the first cyclic compound and the second cyclic compound is obtained.
• Solvents 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, diester Examples include glycerin, polyethylene glycol, and dimethicone. A plurality of these solutions may be used. Further, the sheet may be impregnated and supported by a solution containing components for beauty and medical use, or the components for beauty and medical use may be supported by spraying or vapor deposition.
• the active ingredient other than the first cyclic compound and the second cyclic compound can be similarly supported on the biocompatible membrane.
• the compounds shown in Tables 1 to 3 below were used as the first cyclic compound and the second cyclic compound.
• nicotinamide and leucine acid used in place of the first cyclic compound are shown in Table 2.
• the second cyclic compound may be referred to as a cosmetic agent.
• Example 1 is composed of Example 1A to Example 1I.
• ascorbic acid or sodium ascorbate as the second cyclic compound and nicotinic acid or sodium nicotinate or gallic acid or sodium ferulate or pyridoxal hydrochloride or menthol as the first cyclic compound in the membrane A supported biocompatible membrane was used.
• Example 1A (Production of biocompatible membrane) Cellulose derived from bleached pulp made of wood and having a purity of 90% or more was dissolved in an ionic liquid to prepare a cellulose solution.
• an ionic liquid an ionic liquid in which R 1 is a methyl group and R 2 to R 4 are ethyl groups 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 membrane was 900 nm. Cleaning of the substrate and polymer gel sheet was performed.
• the polymer gel sheet washed in a solution in which sodium ascorbate and sodium nicotinate are dissolved in water is immersed and dried, so that the mass ratio to the membrane is 2.7% sodium ascorbate and sodium nicotinate 0
• a biocompatible membrane carrying the first and second cyclic compounds of Example 1A carrying 2% was obtained.
• the film had a shape of approximately 5 cm square and a transparent appearance.
• 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, and a calibration curve was drawn for the concentration and absorbance at 266 and 220 nm measured with an absorptiometer UV-1600 (Shimadzu Corporation) to obtain slopes a 266 and a 220 , respectively. It was.
• sodium ascorbate was dissolved in ultrapure water, a calibration curve was drawn for the concentration and absorbance at 266 nm, and slope b 266 was obtained.
• 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, the following formula is obtained.
• MEL-300A (Kurashikibo Co., Ltd., hereinafter referred to as MEL) was used.
• EPI-100LLMM long-term maintenance medium Kerrashikibo Co., Ltd., hereinafter referred to as EPI.
• EPI EPI-100LLMM long-term maintenance medium
• Example 1A The membrane of Example 1A was placed on the horny side of MEL, and the membrane surface was moistened with phosphate buffered saline (PBS). The EPI was changed one day after the membrane was installed and once every two days thereafter, and the biocompatible membrane and PBS were changed once every four days.
• PBS phosphate buffered saline
• the cell viability of MEL was determined by the Alamar Blue method.
• a solution obtained by adding 0.20 g Alamar Blue (Cosmo Bio) to 1.8 g EPI was dropped onto the plate, and MEL was installed.
• the fluorescence intensity (excitation wavelength: 544 nm, measurement wavelength: 590 nm) of the culture supernatant was measured with a spectrofluorometer FP-8500 (JASCO).
• the cell viability was calculated as a ratio to the fluorescence intensity when a membrane of Comparative Example 1A described later was added.
• the cultured skin part was cut out from the MEL and moved to a glass bottle. Then, the solution was washed with an equal mass ratio of ethanol and diethyl ether and then with diethyl ether for more than half a day.
• the washed cultured skin site was immersed in a 1M aqueous sodium hydroxide solution to dissolve melanin in the cultured skin.
• the melanin content in the cultured skin was determined by measuring absorbance at 405 nm with an absorptiometer UV-1600 (Shimadzu Corporation) and calculating in advance from a calibration curve based on the dissolved concentration and absorbance of synthetic melanin (Sigma Aldrich Japan Co., Ltd.).
• Example 1B In preparation of the biocompatible membrane of Example 1A, a cosmetic ingredient solution in which sodium ascorbate and nicotinic acid were dissolved was used, and 2.6% sodium ascorbate and 0.2% nicotinic acid were supported as a mass ratio to the membrane. A film was obtained in the same manner as in Example 1A, except that Beauty effect verification was also evaluated by the same method as in Example 1A.
• Example 1C In preparation of the biocompatible membrane of Example 1A, a cosmetic ingredient solution in which ascorbic acid and sodium nicotinate are dissolved is used, and 2.6% ascorbic acid and 0.2% sodium nicotinate are supported as a mass ratio to the membrane. A film was obtained in the same manner as in Example 1A, except that Beauty effect verification was also evaluated by the same method as in Example 1A.
• Example 1D Membrane carrying 2.7% ascorbic acid and 0.2% nicotinic acid as a mass ratio with respect to the membrane using a cosmetic ingredient solution in which ascorbic acid and nicotinic acid are dissolved in the production of the biocompatible membrane of Example 1A
• a film was obtained in the same manner as in Example 1A except that. Beauty effect verification was also evaluated by the same method as in Example 1A.
• Example 1E In the production of the biocompatible membrane of Example 1A, using a cosmetic ingredient solution in which sodium ascorbate and sodium vanillate were dissolved, the mass ratio to the membrane was 2.7% sodium ascorbate and 0.2% sodium vanillate. A membrane was obtained in the same manner as in Example 1A, except that was supported. Beauty effect verification was also evaluated by the same method as in Example 1A.
• Example 1F In preparation of the biocompatible membrane of Example 1A, a cosmetic ingredient solution in which sodium ascorbate and gallic acid were dissolved was used, and 2.7% sodium ascorbate and 0.2% gallic acid were supported as a mass ratio to the membrane. A film was obtained in the same manner as in Example 1A, except that 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, using a cosmetic ingredient solution in which sodium ascorbate and sodium ferulate were dissolved, the mass ratio to the membrane was 2.7% sodium ascorbate and 0.2% sodium ferulate. A membrane was obtained in the same manner as in Example 1A, except that was supported. 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 membrane was obtained in the same manner as in Example 1A, except that was supported. Beauty effect verification was also evaluated by the same method as in Example 1A.
• Example 1I> In the production of the biocompatible membrane of Example 1A, the washed polymer gel sheet was used with a cosmetic 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 membrane was obtained in the same manner as in Example 1A, except that 2% menthol was supported. Ascorbine obtained from the reaction amount using acetic anhydride by determining sodium ascorbate in the membrane by the same method as in Example 1A (Method for quantifying second cyclic compound and first cyclic compound in membrane) The amount of menthol in the membrane was determined by subtracting the amount required for sodium acid. Beauty effect verification was also evaluated by the same method as in Example 1A.
• Comparative Example 1 is composed of Comparative Examples 1A to 1N.
• a biocompatible membrane having no support or a supported biocompatible membrane having only the second cyclic compound or the first cyclic compound was used.
• Example 1A ⁇ Comparative Example 1A>
• a biocompatible membrane was obtained in the same manner as in Example 1A, except that it was not immersed in the cosmetic component solution. Beauty effect verification was also evaluated by the same method as in Example 1A.
• Example 1B ⁇ Comparative Example 1B>
• a cosmetic ingredient solution in which sodium ascorbate was dissolved was used, and the mass ratio with respect to the membrane was loaded with 2.7% sodium ascorbate, as in Example 1A.
• a film was obtained. Beauty effect verification was also evaluated by the same method as in Example 1A.
• Example 1C ⁇ Comparative Example 1C>
• a membrane was prepared in the same manner as in Example 1A, except that a cosmetic ingredient solution in which ascorbic acid was dissolved was used and 2.6% ascorbic acid was supported as a mass ratio to the membrane.
• Got. Beauty effect verification was also evaluated by the same method as in Example 1A.
• Example 1D ⁇ Comparative Example 1D>
• the cosmetic component solution in which sodium nicotinate was dissolved was used, and the mass ratio to the membrane was 0.2% sodium nicotinate supported, as in Example 1A.
• a film was obtained. Beauty effect verification was also evaluated by the same method as in Example 1A.
• Example 1E In the production of the biocompatible membrane of Example 1A, the membrane was used in the same manner as in Example 1A, except that a cosmetic ingredient solution in which nicotinic acid was dissolved was used, and 0.2% nicotinic acid was supported as a mass ratio to the membrane. Got. Beauty effect verification was also evaluated by the same method as in Example 1A.
• Example 1F ⁇ Comparative Example 1F>
• a cosmetic ingredient solution in which sodium vanillate was dissolved was used, and the mass ratio with respect to the membrane was supported in the same manner as in Example 1A except that 0.2% sodium vanillate was supported.
• a film was obtained. Beauty effect verification was also evaluated by the same method as in Example 1A.
• Example 1G ⁇ Comparative Example 1G>
• the membrane was used in the same manner as in Example 1A, except that a cosmetic ingredient solution in which gallic acid was dissolved was used, and 0.2% gallic acid was supported as a mass ratio to the membrane.
• Got. Beauty effect verification was also evaluated by the same method as in Example 1A.
• Example 1H ⁇ Comparative Example 1H>
• a cosmetic ingredient solution in which sodium ferulate was dissolved was used, and the mass ratio to the membrane was the same as that of Example 1A except that 0.2% sodium ferulate was supported.
• the mass ratio to the membrane was the same as that of Example 1A except that 0.2% sodium ferulate was supported.
• Beauty effect verification was also evaluated by the same method as in Example 1A.
• Example 1I ⁇ Comparative Example 1I>
• the cosmetic component solution in which pyridoxal hydrochloride was dissolved was used, and the mass ratio to the membrane was supported as in Example 1A except that 0.2% pyridoxal hydrochloride was supported.
• a film was obtained. Beauty effect verification was also evaluated by the same method as in Example 1A.
• Example 1J ⁇ Comparative Example 1J>
• a membrane was obtained in the same manner as in Example 1A, except that 0.2% menthol was supported as a mass ratio with respect to the membrane using a cosmetic ingredient solution in which menthol was dissolved. It was. Beauty effect verification was also evaluated by the same method as in Example 1A.
• Example 1K ⁇ Comparative Example 1K>
• a cosmetic ingredient solution in which sodium ascorbate and nicotinamide are dissolved is used, and 2.7% sodium ascorbate and 0.2% nicotinamide are supported as a mass ratio to the membrane.
• a film was obtained in the same manner as in Example 1A, except that Beauty effect verification was also evaluated by the same method as in Example 1A.
• Example 1L ⁇ Comparative Example 1L>
• a membrane was prepared in the same manner as in Example 1A, except that a cosmetic ingredient solution in which nicotinamide was dissolved was used and a 0.2% nicotinamide was supported as a mass ratio to the membrane.
• Got. Beauty effect verification was also evaluated by the same method as in Example 1A.
• Example 1M ⁇ Comparative Example 1M>
• a cosmetic ingredient solution in which sodium ascorbate and leucine acid were dissolved, and 2.7% sodium ascorbate and 0.2% leucine acid were supported as a mass ratio to the membrane.
• a film was obtained in the same manner as in Example 1A, except that Beauty effect verification was also evaluated by the same method as in Example 1A.
• Example 1N ⁇ Comparative Example 1N>
• a membrane was prepared in the same manner as in Example 1A, except that a cosmetic ingredient solution in which leucine acid was dissolved and 0.2% leucine acid was supported as a mass ratio to the membrane.
• Got. Beauty effect verification was also evaluated by the same method as in Example 1A.
• Example 1 ⁇ Consideration of Example 1> Table 4 shows the amount of ascorbic acid or sodium ascorbate cultured on the skin per day [ ⁇ mol / day] of Examples 1A-1I and Comparative Examples 1A-1N and melanin produced in the cultured skin during the two-week culture period. The yield [ ⁇ g / well] is shown. The cell viability was confirmed to be 90% or more in both Examples and Comparative Examples.
• Example 1A and Comparative Examples 1A, 1B, and 1D are compared, the loading of 2.7% sodium ascorbate and 0.2% sodium nicotinate results in the second cyclic compound (beauty agent). The amount of permeation improved dramatically and the melanin output was reduced.
• Example 1B Comparing Example 1B with Comparative Examples 1A, 1B and 1E, the loading of 2.6% sodium ascorbate and 0.2% nicotinic acid dramatically improved the amount of permeation of the second cyclic compound and produced melanin. The amount was reduced.
• Example 1C Comparing Example 1C with Comparative Examples 1A, 1C, and 1D, the loading 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.
• Example 1D Comparing Example 1D with Comparative Examples 1A, 1C and 1E, the loading of 2.7% ascorbic acid and 0.2% nicotinic acid dramatically improved the permeation amount of the second cyclic compound and produced melanin. Was lowered.
• Example 1E Comparing Example 1E with Comparative Examples 1A, 1B and 1F, the loading 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.
• Example 1F When Example 1F is compared with Comparative Examples 1A, 1B, and 1G, the loading of 2.7% sodium ascorbate and 0.2% gallic acid significantly improves the permeation amount of the second cyclic compound, and melanin. The output was reduced.
• Example 1G and Comparative Examples 1A, 1B and 1H are compared, the amount of permeation of the second cyclic compound is dramatically improved by loading 2.7% sodium ascorbate and 0.2% sodium ferulate. Melanin output was reduced.
• Example 1H Comparing Example 1H with Comparative Examples 1A, 1B and 1I, the loading of 2.7% sodium ascorbate and 0.2% pyridoxal hydrochloride significantly improved the permeation amount of the second cyclic compound, Melanin output was reduced.
• Example 1I Comparing Example 1I with Comparative Examples 1A, 1B and 1J, the loading of 2.7% sodium ascorbate and 0.2% menthol significantly improved the permeation amount of the second cyclic compound and produced melanin. The amount was reduced.
• Comparative Example 1K Comparative Example 1K with Comparative Examples 1A, 1B and 1L, 2.7% sodium ascorbate and 0.2% nicotinamide were supported, so that the permeation amount of the second cyclic compound was not improved, and melanin yield was increased. It turns out that it was not able to be lowered.
• Example 2 is composed of Examples 2A-2G. The amount of reduced ascorbic acid over a long period of sodium ascorbate in the biocompatible membrane prepared in Example 1 was investigated.
• Example 2A In producing the biocompatible membrane of Example 1A, a biocompatible membrane was obtained in the same manner as in Example 1A.
• the biocompatible membrane stored for one week for four weeks under the initial condition and 20 ° C. was immersed in 2 g of ultrapure water and ultrasonically cleaned for 1 hour.
• the amount of reduced ascorbic acid in the solution was quantified with an ascorbic acid quantification kit (BioVision), normalized with the amount of sodium ascorbate contained in the initial membrane, and the ratio of reduced ascorbic acid was determined.
• Example 2B In producing 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 one week and four weeks with respect to the initial stage was determined.
• Example 2C In producing 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 one week and four weeks with respect to the initial stage was determined.
• Example 2D In producing 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 one week and four weeks with respect to the initial stage was determined.
• Example 2E In producing 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 one week and four weeks with respect to the initial stage was determined.
• Example 2F In producing 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 one week and four weeks with respect to the initial stage was determined.
• Example 2G In producing 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 one week and four weeks with respect to the initial stage was determined.
• Comparative Example 2 is composed of Comparative Examples 2A-2G.
• the amount of reduced ascorbic acid was determined by an aqueous solution in which sodium ascorbate and the first cyclic compound were dissolved.
• ⁇ 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, was prepared. In the same manner as in Example 1A, the ratio of reduced ascorbic acid after storage for one week and four 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 in which 3.0% and 0.2% sodium ascorbate and sodium vanillate were dissolved in a mass ratio to the solution was prepared. In the same manner as in Example 1A, the ratio of reduced ascorbic acid after storage for one week and four weeks with respect to the initial stage was determined.
• ⁇ Comparative Example 2D> An aqueous solution was prepared in the same manner as Comparative Example 2A, except that PBS containing 3.0% and 0.2% sodium ascorbate and gallic acid dissolved in a mass ratio to the solution was prepared. In the same manner as in Example 1A, the ratio of reduced ascorbic acid after storage for one week and four 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 containing 3.0% and 0.2% sodium ascorbate and sodium ferulate dissolved in a mass ratio to the solution was prepared. In the same manner as in Example 1A, the ratio of reduced ascorbic acid after storage for one week and four 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, was prepared. In the same manner as in Example 1A, the ratio of reduced ascorbic acid after storage for one week and four weeks with respect to the initial stage was determined.
• ⁇ Comparative Example 2G> An aqueous solution was prepared in the same manner as Comparative Example 2A, except that PBS containing 3.0% and 0.2% sodium ascorbate and menthol dissolved in a mass ratio to the solution was prepared. In the same manner as in Example 1A, the ratio of reduced ascorbic acid after storage for one week and four weeks with respect to the initial stage was determined.
• Table 5 shows the ratio of reduced ascorbic acid to the initial amount after one week and four weeks after Example 2A-2F and Comparative Example 2A-2F.
• reduced ascorbic acid could be stably held for at least four weeks by drying and supporting ascorbic acid in the sheet.
• Example 3 is composed of Example 3A to Example 3F.
• a biocompatible membrane having sodium ascorbate as the second cyclic compound and sodium nicotinate as the first cyclic compound was used in the membrane.
• Example 3A In the production of the biocompatible membrane of Example 1A, using a cosmetic ingredient solution in which sodium ascorbate and sodium nicotinate were dissolved, the mass ratio to the membrane was 0.5% sodium ascorbate and 0.1% sodium nicotinate. A membrane was obtained in the same manner as in Example 1A, except that was supported. Beauty effect verification was also evaluated by the same method as in Example 1A.
• Example 3B In the production of the biocompatible membrane of Example 1A, the washed polymer gel sheet was immersed in a cosmetic component solution in which sodium ascorbate and sodium nicotinate were dissolved, so that the mass ratio to the membrane was 0.5% ascorbic acid. A membrane was obtained in the same manner as in Example 1A, except that sodium and 0.2% sodium nicotinate were supported. Beauty effect verification was also evaluated by the same method as in Example 1A.
• Example 3C In the production of the biocompatible membrane of Example 1A, using a cosmetic ingredient solution in which sodium ascorbate and sodium nicotinate were dissolved, the mass ratio to the membrane was 0.8% sodium ascorbate and 0.1% sodium nicotinate. A membrane was obtained in the same manner as in Example 1A, except that was supported. Beauty effect verification was also evaluated by the same method as in Example 1A.
• Example 3D In the production of the biocompatible membrane of Example 1A, using a cosmetic ingredient solution in which sodium ascorbate and sodium nicotinate were dissolved, the mass ratio to the membrane was 0.8% sodium ascorbate and 0.2% sodium nicotinate. A membrane was obtained in the same manner as in Example 1A, except that was supported. 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, using a cosmetic ingredient solution in which sodium ascorbate and sodium nicotinate were dissolved, the mass ratio to the membrane was 0.8% sodium ascorbate and 4.6% sodium nicotinate. A membrane was obtained in the same manner as in Example 1A, except that was supported. Beauty effect verification was also evaluated by the same method as in Example 1A.
• Example 3F In the production of the biocompatible membrane of Example 1A, using a cosmetic ingredient solution in which sodium ascorbate and sodium nicotinate were dissolved, the mass ratio to the membrane was 4.6% sodium ascorbate and 0.2% sodium nicotinate. A membrane was obtained in the same manner as in Example 1A, except that was supported. Beauty effect verification was also evaluated by the same method as in Example 1A.
• Comparative Example 3 is composed of Comparative Examples 3A to 3D.
• Comparative Example 3 a biocompatible membrane in which only sodium ascorbate or sodium nicotinate was supported was used.
• Example 3A ⁇ Comparative Example 3A>
• a cosmetic ingredient solution in which sodium nicotinate was dissolved was used, and the mass ratio to the membrane was the same as that of Example 1A except that 0.1% sodium nicotinate was supported.
• the mass ratio to the membrane was the same as that of Example 1A except that 0.1% sodium nicotinate was supported.
• Beauty effect verification was also evaluated by the same method as in Example 1A.
• Example 3B ⁇ Comparative Example 3B>
• a cosmetic ingredient solution in which sodium nicotinate was dissolved was used, and the mass ratio to the membrane was supported by 4.6% sodium nicotinate, as in Example 1A.
• Beauty effect verification was also evaluated by the same method as in Example 1A.
• Example 3D ⁇ Comparative Example 3D>
• a cosmetic ingredient solution in which sodium ascorbate was dissolved was used, and the mass ratio to the membrane was the same as in Example 1A, except that 0.8% sodium ascorbate was supported.
• a film. Beauty effect verification was also evaluated by the same method as in Example 1A.
• Example 3 ⁇ Consideration of Example 3> Table 6 shows cultured skin permeation amount [ ⁇ mol / day] of sodium ascorbate after 1 day of Examples 1A, 3A to 3F and Comparative Examples 1A, 1B, 1D and 3A to 3D, and cultured skin during the two-week culture period.
• the melanin yield [ ⁇ g / well] produced in (1) was shown.
• the cell viability was confirmed to be 90% or more in both Examples and Comparative Examples.
• Table 6 shows that when a biocompatible membrane carrying 0.5% or more of sodium ascorbate and 0.1% or more of sodium nicotinate and PBS are used, the permeation amount of the second cyclic compound is increased and melanin is produced. The amount was significantly reduced.
• Example 4 Based on Example 1A, the melanin production amount was examined using a 10% glycerol, 5% propanediol, and 85% mass PBS solution in place of PBS in the verification of the cosmetic effect.
• Example 4A In the production of the biocompatible membrane of Example 1A, a biocompatible membrane was obtained in the same manner as in Example 1A. In cosmetic effect verification, cosmetic effect verification was performed according to Example 1A, except that PBS containing 10% glycerol by mass and 5% propanediol by mass was used instead of PBS alone.
• Table 7 shows the cultured skin permeation amount [ ⁇ mol / day] of sodium ascorbate after 1 day of Examples 1A, 4A and Comparative Example 1A, and the melanin output [ ⁇ g / day] produced in the cultured skin during the two-week culture period. well].
• the cell viability was confirmed to be 90% or more in both Examples and Comparative Examples.
• Example 4A when Example 4A is compared with Example 1A and Comparative Example 1A, the melanin yield is more than that of PBS by using a PBS solution containing 10% glycerol and 5% propanediol rather than PBS alone. It can be seen that it can be suppressed.
• Example 5 is composed of Examples 5A to 5F.
• a biocompatible membrane in which only sodium ascorbate was supported in the membrane was prepared, and PBS to which sodium nicotinate was added in place of PBS was used in the cosmetic effect verification.
• Example 5A In producing the biocompatible membrane of Example 1A, a biocompatible membrane was obtained in the same manner as in Comparative Example 3C. In the cosmetic effect verification, evaluation was performed in the same manner as in Example 1A, except that PBS added with sodium nicotinate having a mass ratio of 0.10% to the biocompatible membrane was used instead of PBS.
• Example 5B In producing the biocompatible membrane of Example 1A, a biocompatible membrane was obtained in the same manner as in Comparative Example 3C. In the cosmetic effect verification, evaluation was performed in the same manner as in Example 1A, except that PBS added with sodium nicotinate having a mass ratio of 0.20% to the biocompatible membrane was used instead of PBS.
• Example 5C In the production of the biocompatible membrane of Example 1A, a biocompatible membrane was obtained in the same manner as in Comparative Example 3D. In the cosmetic effect verification, the evaluation was performed in the same manner as in Example 1A, except that PBS added with sodium nicotinate having a mass ratio of 0.10% with respect to the biocompatible membrane was used instead of PBS.
• Example 5D In the production of the biocompatible membrane of Example 1A, a biocompatible membrane was obtained in the same manner as in Comparative Example 3D. In the cosmetic effect verification, evaluation was performed in the same manner as in Example 1A, except that PBS added with sodium nicotinate having a mass ratio of 0.20% to the biocompatible membrane was used instead of PBS.
• Example 5E In the production of the biocompatible membrane of Example 1A, a biocompatible membrane was obtained in the same manner as in Comparative Example 3D. In the cosmetic effect verification, evaluation was performed in the same manner as in Example 1A, except that PBS added with sodium nicotinate having a mass ratio of 5.0% with respect to the biocompatible membrane was used instead of PBS.
• Example 5F In producing the biocompatible membrane of Example 1A, a biocompatible membrane was obtained in the same manner as in Comparative Example 1B. In the cosmetic effect verification, evaluation was performed in the same manner as in Example 1A, except that PBS added with sodium nicotinate having a mass ratio of 0.20% to the biocompatible membrane was used instead of PBS.
• Comparative Example 4 is composed of Comparative Examples 4A to 4C.
• PBS added with sodium nicotinate was used instead of PBS.
• ⁇ Comparative Example 4A> In the production of the biocompatible membrane of Example 1A, a biocompatible membrane was obtained in the same manner as in Comparative Example 1A. In the cosmetic effect verification, the evaluation was performed in the same manner as in Example 1A, except that PBS added with sodium nicotinate having a mass ratio of 0.10% with respect to the biocompatible membrane was used instead of PBS.
• ⁇ Comparative Example 4B> In the production of the biocompatible membrane of Example 1A, a biocompatible membrane was obtained in the same manner as in Comparative Example 1A. In the cosmetic effect verification, evaluation was performed in the same manner as in Example 1A, except that PBS added with sodium nicotinate having a mass ratio of 0.20% to the biocompatible membrane was used instead of PBS.
• Table 8 shows cultured skin permeation amount [ ⁇ mol / day] of sodium ascorbate one day after 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 melanin yield [ ⁇ g / well] produced in (1) was shown.
• the cell viability was confirmed to be 90% or more in both Examples and Comparative Examples.
• Example 6 is composed of Examples 6A to 6C.
• 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 cosmetic effect verification.
• Example 6A In the production of the biocompatible membrane of Example 1A, a biocompatible membrane was obtained in the same manner as in Comparative Example 3D. In the cosmetic effect verification, evaluation was performed in the same manner as in Example 1A, except that PBS added with nicotinic acid having a mass ratio of 0.20% to the biocompatible membrane was used instead of PBS.
• Example 6B In producing the biocompatible membrane of Example 1A, a biocompatible membrane was obtained in the same manner as in Comparative Example 1B. In the cosmetic effect verification, evaluation was performed in the same manner as in Example 1A, except that PBS added with nicotinic acid having a mass ratio of 0.20% to the biocompatible membrane was used instead of PBS.
• Example 6C In producing the biocompatible membrane of Example 1A, a biocompatible membrane was obtained in the same manner as in Comparative Example 1B. In the cosmetic effect verification, evaluation was performed in the same manner as in Example 1A, except that PBS added with nicotinic acid having a mass ratio of 2.0% with respect to the biocompatible membrane was used instead of PBS.
• Comparative Example 5 is composed of Comparative Examples 5A to 5B.
• PBS to which nicotinic acid was added was used instead of PBS in the biocompatible film and the cosmetic effect verification.
• ⁇ Comparative Example 5A> In the production of the biocompatible membrane of Example 1A, a biocompatible membrane was obtained in the same manner as in Comparative Example 1A. In the cosmetic effect verification, evaluation was performed in the same manner as in Example 1A, except that PBS added with nicotinic acid having a mass ratio of 0.20% to the biocompatible membrane was used instead of PBS.
• ⁇ Comparative Example 5B> In the production of the biocompatible membrane of Example 1A, a biocompatible membrane was obtained in the same manner as in Comparative Example 1A. In the cosmetic effect verification, evaluation was performed in the same manner as in Example 1A, except that PBS added with nicotinic acid having a mass ratio of 2.0% with respect to the biocompatible membrane was used instead of PBS.
• Table 9 shows the amount of sodium ascorbate permeated in cultured skin [ ⁇ mol / day] one day after Examples 6A to 6C and Comparative Examples 1A, 1B, 3D, 5A, and 5B, and produced in cultured skin during a two-week culture period.
• the produced melanin output [ ⁇ g / well] is shown.
• the cell viability was confirmed to be 90% or more in both Examples and Comparative Examples.
• Example 7 is composed of Example 7A.
• a biocompatible membrane in which only sodium ascorbate was supported in the membrane was prepared, and PBS to which gallic acid was added instead of PBS was used in the cosmetic effect verification.
• Example 7A In producing the biocompatible membrane of Example 1A, a biocompatible membrane was obtained in the same manner as in Comparative Example 1B. In the cosmetic effect verification, evaluation was performed in the same manner as in Example 1A, except that PBS added with gallic acid having a mass ratio of 0.20% to the biocompatible membrane was used instead of PBS.
• Comparative Example 6 is composed of Comparative Example 6A.
• a biocompatible membrane was prepared, and PBS to which gallic acid was added instead of PBS was used in the verification of the cosmetic effect.
• ⁇ Comparative Example 6A> In the production of the biocompatible membrane of Example 1A, a biocompatible membrane was obtained in the same manner as in Comparative Example 1A. In the cosmetic effect verification, evaluation was performed in the same manner as in Example 1A, except that PBS added with gallic acid having a mass ratio of 0.20% to the biocompatible membrane was used instead of PBS.
• Table 10 shows the culture skin permeation amount [ ⁇ mol / day] of sodium ascorbate one day after Example 7A and Comparative Examples 1B and 6A, and the melanin production amount [ ⁇ g / day] produced in the cultured skin during the two-week culture period. well].
• the cell viability was confirmed to be 90% or more in both Examples and Comparative Examples.
• Example 8 is composed of Example 8A.
• 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 cosmetic effect verification.
• Example 8A In producing the biocompatible membrane of Example 1A, a biocompatible membrane was obtained in the same manner as in Comparative Example 1B. In the cosmetic effect verification, evaluation was performed in the same manner as in Example 1A, except that PBS added with menthol having a mass ratio of 0.20% to the biocompatible membrane was used instead of PBS.
• Comparative Example 7 is composed of Comparative Example 7A.
• a biocompatible membrane was prepared, and a solution to which menthol was added instead of PBS was used in cosmetic effect verification.
• ⁇ Comparative Example 7A> In the production of the biocompatible membrane of Example 1A, a biocompatible membrane was obtained in the same manner as in Comparative Example 1A. In the cosmetic effect verification, evaluation was performed in the same manner as in Example 1A, except that a solution containing menthol having a mass ratio of 0.20% with respect to the biocompatible membrane was used instead of PBS.
• Example 8 ⁇ Consideration of Example 8> Table 11 shows the amount of sodium ascorbate permeated in cultured skin [ ⁇ mol / day] one day after Example 8A and Comparative Examples 1B and 7A, and the amount of melanin produced in cultured skin during a two-week culture period [ ⁇ g / day]. well]. The cell viability was confirmed to be 90% or more in both Examples and Comparative Examples.
• Example 9 is composed of Example 9A.
• a biocompatible membrane in which only gallic acid was supported in the membrane was prepared, and PBS to which sodium ascorbate was added in place of PBS was used in the cosmetic effect verification.
• Example 9A In producing the biocompatible membrane of Example 1A, a biocompatible membrane was obtained in the same manner as in Comparative Example 1G. In the cosmetic effect verification, evaluation was performed in the same manner as in Example 1A, except that PBS added with sodium ascorbate having a mass ratio of 3.0% with respect to the biocompatible membrane was used instead of PBS.
• Comparative Example 8 is composed of Comparative Example 8A.
• a biocompatible membrane was prepared, and PBS to which sodium ascorbate was added in place of PBS was used in the cosmetic effect verification.
• ⁇ Comparative Example 8A> In the production of the biocompatible membrane of Example 1A, a biocompatible membrane was obtained in the same manner as in Comparative Example 1A. In the cosmetic effect verification, evaluation was performed in the same manner as in Example 1A, except that PBS added with sodium ascorbate having a mass ratio of 3.0% with respect to the biocompatible membrane was used instead of PBS.
• Table 12 shows the amount of sodium ascorbate permeated in cultured skin [ ⁇ mol / day] one day after Example 9A and Comparative Examples 1G and 8A, and the amount of melanin produced in the cultured skin during a two-week culture period [ ⁇ g / day]. well].
• the cell viability was confirmed to be 90% or more in both Examples and Comparative Examples.
• Example 10 is composed of Example 10A.
• 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 cosmetic effect verification.
• Example 10A In producing the biocompatible membrane of Example 1A, a biocompatible membrane was obtained in the same manner as in Comparative Example 1J. In the cosmetic effect verification, evaluation was performed in the same manner as in Example 1A, except that PBS added with sodium ascorbate having a mass ratio of 3.0% with respect to the biocompatible membrane was used instead of PBS.
• Table 13 shows the cultured skin permeation amount [ ⁇ mol / day] of sodium ascorbate one day after Example 10A and Comparative Examples 1J and 8A, and the melanin output [ ⁇ g / day] produced in the cultured skin during the two-week culture period. well].
• the cell viability was confirmed to be 90% or more in both Examples and Comparative Examples.
• Example 11 is composed of Example 11A.
• a biocompatible membrane was prepared in which arbutin and gallic acid were supported in the membrane, and PBS was used in the cosmetic effect verification.
• Example 11A In the preparation of the biocompatible membrane of Example 1A, arbutin was used in place of sodium ascorbate, and gallic acid was used in place of sodium nicotinate, and the mass ratio of arbutin and gallic acid in the membrane to the membrane was 2.3, 0. A biocompatible membrane was obtained in the same manner as in Example 1A, except that the content was 2%. In the verification of the beauty effect, evaluation was performed in the same manner as in Example 1A.
• Comparative Example 9 is composed of Comparative Example 9A.
• a biocompatible membrane in which arbutin was supported in the membrane was prepared, and PBS was used in the cosmetic effect verification.
• Table 14 shows the amount of arbutin cultured through the skin [ ⁇ mol / day] one 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 [ ⁇ g / well]. showed that.
• the cell viability was confirmed to be 90% or more in both Examples and Comparative Examples.
• Example 12 is composed of Example 12A.
• 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 production of the biocompatible membrane of Example 1A, ellagic acid was used instead of sodium ascorbate, gallic acid was used instead of sodium nicotinate, and the mass ratio of ellagic acid and gallic acid in the membrane to the membrane was 0.5, A biocompatible membrane was obtained in the same manner as in Example 1A, except that the content was 0.2%. In the cosmetic effect verification, the evaluation was performed in the same manner as in Example 1A.
• Comparative Example 10 is composed of Comparative Example 10A.
• a biocompatible membrane in which ellagic acid was supported in the membrane was prepared, and PBS was used in the cosmetic effect verification.
• Example 10A In the production 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 0.5%, as in Example 1A. A biocompatible membrane was obtained. In the verification of the beauty effect, evaluation was performed in the same manner as in Example 1A.
• Example 12 ⁇ Consideration of Example 12> Table 15 shows cultured skin permeation amount [ ⁇ mol / day] of ellagic acid one day after Example 12A and Comparative Examples 10A and 1G, and melanin production amount [ ⁇ g / well] produced in cultured skin during a two-week culture period. ]showed that. The cell viability was confirmed to be 90% or more in both Examples and Comparative Examples.
• Example 13 is composed of Example 13A.
• a biocompatible membrane in which sodium ascorbate and syringic acid were supported in the membrane was prepared, and PBS was used in the verification of the cosmetic effect.
• Example 13A> In the production of the biocompatible membrane of Example 1A, syringic acid was used in place of sodium nicotinate, the target thickness was 2700 nm, and the mass ratio of ascorbic acid and syringic acid in the membrane to the membrane was 9.8, 0.00, respectively. A biocompatible membrane was obtained in the same manner except that 9% was supported. In cosmetic effect verification, evaluation was performed in the same manner as in Example 1A, except that PBS was used.
• Example 13 ⁇ Consideration of Example 13> Table 16 shows the amount of sodium ascorbate cultured permeated [ ⁇ mol / day] 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 [ ⁇ g / well]. showed that. The cell viability was confirmed to be 90% or more in both Examples and Comparative Examples.
• the cosmetics or medical materials of the present disclosure can be suitably used in various fields such as the beauty field and the pharmaceutical field.

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