JP2021020861A - Film for sticking to living body, sheet for sticking to living body, kit, and cosmetic method - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a membrane for attaching to a living body, which is advantageous from the viewpoint of appropriately adjusting the release of a predetermined component when attached to a living body using a predetermined mounting liquid. SOLUTION: A membrane for attaching to a living body (10a) has a structure (15) containing regenerated cellulose, a polymer having an SP value of 20 MPa1 / 2 or more and 30 MPa1 / 2 or less, and a receptor stimulating component (20). Contains. The film for attaching to a living body (10a) has a thickness of 20 nm or more and 2000 nm or less. [Selection diagram] Fig. 1

Description

The present disclosure relates to a biological attachment film, a biological attachment sheet, a kit, and a beauty method.

Conventionally, a technique for controlling the release of components such as drugs has been known.

For example, Patent Document 1 describes drug-containing particles in which a drug is carried inside porous particles made of a cellulosic material such as cellulose, a cellulose derivative, or regenerated cellulose. For example, the outer surface of the drug-containing particles can be coated to impart drug release controllability. As a result, for example, an orally administered preparation having excellent drug release controllability is provided.

Patent Document 2 describes a transdermal drug delivery device including a support film, a first adhesive layer, and a protective release liner. The first adhesive layer contains a solid dispersion containing a first adhesive, a first amorphous therapeutic agent, and a polymeric stabilizer and dispersant. Polymeric stabilizers and dispersants contain hydrogen bond forming functional groups. When the transdermal drug delivery device is applied to the skin, the active pharmaceutical ingredient is delivered percutaneously. In the application of the transdermal drug delivery device to the skin, the release liner is removed and the first adhesive layer comes into contact with and adheres to the skin.

Japanese Unexamined Patent Publication No. 9-87203 Japanese Patent Publication No. 2011-521974

The technique described in Patent Document 1 is a technique for oral administration of a component such as a drug, and is not a technique intended to be attached to a living body. The technique described in Patent Document 2 is not intended to release a therapeutic agent from a transdermal drug delivery device using a predetermined mounting solution.

Therefore, the present disclosure provides a biological attachment film that is advantageous from the viewpoint of appropriately adjusting the release of a predetermined component when attached to a living body using a predetermined mounting solution.

This disclosure is
Has a structure containing regenerated cellulose
A polymer having 20 MPa ^1/2 or more 30 MPa ^1/2 or less of the SP value, contains a receptor stimulation component,
It has a thickness of 20 nm or more and 2000 nm or less.
A membrane for attaching to a living body is provided.

The above-mentioned membrane for attaching to a living body is advantageous from the viewpoint of appropriately adjusting the release of a receptor stimulating component when attached to a living body using a predetermined mounting solution.

FIG. 1 is a cross-sectional view schematically showing an example of the biological attachment film of the present disclosure. FIG. 2 is a cross-sectional view schematically showing another example of the biological attachment membrane of the present disclosure. FIG. 3A is a diagram showing an example of a method for attaching the biological attachment film of the present disclosure. FIG. 3B is a diagram showing an example of a method for attaching the biological attachment film of the present disclosure. FIG. 3C is a diagram showing an example of a method for attaching the biological attachment film of the present disclosure. FIG. 4 is a cross-sectional view schematically showing another example of the biological attachment sheet of the present disclosure.

(Knowledge on which this disclosure was based)
It is conceivable that the membrane for attaching to the living body contains the receptor stimulating component, and the receptor stimulating component is released toward the living body using a predetermined mounting solution. The present inventors have tried to utilize a film having a structure containing regenerated cellulose as such a film for attaching to a living body. As a result, the present inventors have found that further ingenuity is required to appropriately regulate the release of the receptor stimulating component. In particular, the present inventors have found that a new device is required to continue the release of the receptor stimulating component for a long time and to maintain the stimulation by the receptor stimulating component for a long time. Therefore, the present inventors have made extensive studies on a technique for appropriately adjusting the release of the receptor stimulating component in the membrane for biological application. As a result, when the membrane having a structure containing regenerated cellulose contains a predetermined polymer, the permeation rate of the mounting solution in the membrane for biological application is appropriately adjusted, and the receptor stimulating component is used. We have newly found that the release can be adjusted appropriately. Based on this new finding, the present inventors have devised the bioadhesive film of the present disclosure.

(Embodiment)
Hereinafter, embodiments of the present disclosure will be described with reference to the drawings. The following embodiments are merely examples, and the biological attachment membrane of the present disclosure is not limited to the following embodiments. Matters such as numerical values, shapes, materials, components, arrangement of components, connection modes, and steps and step order shown in the following embodiments are examples and are described for the purpose of limiting the present disclosure. It's not something. The various embodiments below can be combined with each other as long as there is no conflict. In addition, among the components in the following embodiments, the components not described in the independent claims indicating the highest level concept should not be understood as essential components. In the following description, components having substantially the same function are indicated by common reference numerals, and the description may be omitted. In addition, some elements may be omitted in order to avoid overly complicated drawings.

The biological attachment film 10a shown in FIG. 1 has a structure 15 containing regenerated cellulose. Biological sticking film 10a is contains a polymer having 20 MPa ^1/2 or more 30 MPa ^1/2 or less of the SP value, and a receptor stimulation component 20. The film for attaching to a living body 10a has a thickness of 20 nm or more and 2000 nm or less. Below, a polymer having a 20MPa ^1/2 more than 30MPa ^1/2 or less of the SP value referred to as "polymer M _SP20-30". The thickness of the biological attachment film 10a is determined, for example, by measuring the thickness of the biological attachment film 10a at a plurality of locations and averaging them. The thickness at each location can be measured using, for example, a stylus profiling system (manufactured by Bruker Nano Incorporated, product name: DEKTAK®).

The structure 15 containing regenerated cellulose makes it possible to retain the receptor stimulating component 20 in the biological attachment film 10a. "Retainable" means that the receptor stimulating component 20 or the like forms a layer in the biological attachment film 10a in a state where the biological attachment film 10a is not destroyed or deformed, or the biological attachment film 10a. It may be in a state in which a component such as the receptor stimulating component 20 is incorporated. The structure 15 containing regenerated cellulose may contain regenerated cellulose as a main component. In the present specification, the "main component" means the component contained most in terms of mass.

The film 10a for attaching to a living body may have a thickness of 200 nm or more and 2000 nm or less. When the thickness of the biological attachment film 10a is 200 nm or more, the biological attachment film 10a has high strength and is easy to handle. Therefore, the biological attachment film 10a can function as a self-supporting film that can be attached to a biological tissue such as skin. When the thickness of the biological attachment film 10a is 2000 nm or less, the biological attachment film 10a is difficult to peel off when the biological attachment film 10a is attached to a biological tissue. Further, when the thickness of the biological attachment film 10a is within such a range, for example, the biological attachment film 10a can be easily peeled off from the biological tissue by running water. The film 10a for attaching to a living body may have a thickness of 200 nm or more and 1000 nm or less. When the thickness of the biological attachment film 10a is 1000 nm or less, the presence of the biological attachment film 10a is reduced, and it is possible to more naturally hide spots and the like. The biological attachment film 10a may have a thickness of 200 nm or more and 500 nm or less. When the thickness of the biological attachment film 10a is 500 nm or less, for example, the presence of the biological attachment film 10a is almost eliminated, and a portion such as a stain can be naturally hidden. The film 10a for attaching to a living body may have a thickness of 500 nm or more and 1000 nm or less. In this case, for example, it is easy to handle because the strength of the film can be further increased while naturally hiding the spots and the like on the film 10a for attaching to the living body.

When the biological attachment film 10a is attached to the living body using a predetermined mounting solution, the release of the receptor stimulating component 20 is likely to be appropriately adjusted by the action of the polymer M _SP20-30 . This is because the polymer M _SP20-30 has a low affinity with the mounting solution, the speed at which the mounting solution permeates the inside of the bio-attached film 10a, and the mounting solution from the inside of the bio-attached film 10a to the outside of the bio-attached film 10a. This is because the speed at which the liquid moves tends to be slowed down. As a result, it is easy to continue the release of the receptor stimulating component 20 for a long time. On the other hand, the affinity between the polymer M _SP20-30 and the regenerated cellulose is high, and the polymer M _SP20-30 can be retained in the biological attachment film 10a.

The SP value of the polymer M _SP20-30 is more preferably 20 MPa ^1/2 or more and 25 MPa ^1/2 or less. In this case, the polymer M _SP20-30 is hardly dissolved in the predetermined mounting solution, but the mounting solution can be appropriately permeated. Therefore, the speed at which the mounting liquid permeates the inside of the biological sticking film 10a and the speed at which the mounting liquid moves from the inside of the biological sticking film 10a to the outside of the biological sticking film 10a can be easily adjusted to a desired level. As a result, the release of the receptor stimulating component 20 can be more reliably continued for a long period of time.

The regenerated cellulose is, for example, cellulose substantially represented by the following formula (I). Here, "substantially the cellulose represented by the formula (I)" means the cellulose in which the hydroxyl group of the glucose residue in the cellulose represented by the formula (I) remains 90% or more. The ratio of the number of hydroxyl groups of glucose residues in cellulose contained in the membrane to the number of hydroxyl groups of glucose residues in cellulose represented by the formula (I) is known, for example, by X-ray photoelectron spectroscopy (XPS). It can be quantified by the method of. In some cases, the regenerated cellulose contained in the biological attachment film 10a may contain a branched structure. Artificially derivatized cellulose typically does not fall under "substantially the cellulose represented by formula (I)". On the other hand, the cellulose regenerated through derivatization is not excluded from the "cellulose represented by the formula (I) substantially". Even cellulose that has been derivatized and regenerated may fall under "substantially the cellulose represented by the formula (I)".

Regenerated cellulose has, for example, a weight average molecular weight of 100,000 or more. Cellulose has a molecular structure containing many hydroxyl groups. In a membrane composed of cellulose, many hydrogen bonds are likely to occur inside or between molecules. Therefore, the film made of cellulose tends to have higher strength than the film made of other organic polymers. However, the strength of the film formed from a suspension in which natural cellulose fibers are dispersed in a dispersion medium such as water is borne by hydrogen bonds between the nanofibers constituting the cellulose fibers. Therefore, such a film has room for higher strength. On the other hand, in the structure 15 containing regenerated cellulose, the nanofibers are in a state of being loosened to the unit of the molecular chain, so that the strength of the structure 15 containing regenerated cellulose is borne by the hydrogen bonds between the cellulose molecular chains. In the structure 15 containing regenerated cellulose, hydrogen bonds between units smaller than those of nanofibers are likely to be formed. Therefore, the structure 15 containing regenerated cellulose has higher strength and appropriate flexibility as compared with a membrane formed from a suspension in which fibers of natural cellulose are dispersed in a dispersion medium such as water. Have. Therefore, when the biological attachment film 10a has a structure 15 containing regenerated cellulose, even if the thickness of the biological attachment film 10a is in the range of 20 nm or more and 2000 nm or less, the biological attachment film 10a is not easily torn and is easy to handle. In addition, "nanofiber" is also called "nanofibril or microfibril", and is the most basic unit in which cellulose molecules are aggregated, and has a wire diameter of about 4 nm or more and about 100 nm or less and a length of about 1 μm or more. ..

It is advantageous that the regenerated cellulose has a weight average molecular weight of 100,000 or more in the bioattachment film 10a from the viewpoint of increasing the strength of the bioadhesion film 10a. This is because, in addition to increasing the strength along the extending direction of the molecular chain, more hydroxyl groups are contained in each molecular chain, so that the formation of more hydrogen bonds between the molecules increases the strength of the film. Because it can be considered. The weight average molecular weight of regenerated cellulose can be determined by gel permeation chromatography (GPC). A sample for GPC measurement can be prepared by extracting the receptor stimulating component 20 from the biological attachment membrane 10a.

As used herein, "regenerated cellulose" means cellulose that does not have the crystal structure I peculiar to natural cellulose. The crystal structure of cellulose can be confirmed by the XRD pattern. Natural cellulose has peaks around 14-17 ° and 23 °, which are peculiar to crystal structure I, in the XRD pattern using CuKα rays, but regenerated cellulose often has crystal structure II, 12 ° and 20 °. It has peaks near ° and 22 ° and no peaks near 14-17 ° and 23 °.

For example, 90% or more of the regenerated cellulose contained in the bioadhesive film 10a is regenerated cellulose that has not been chemically modified or derivatized. 98% or more of the regenerated cellulose contained in the bioadhesive film 10a based on the mass may be regenerated cellulose that has not been chemically modified or derivatized. In this case, it is considered that the film 10a for attaching to a living body contains a large amount of regenerated cellulose that has not been chemically modified or derivatized, and contains a larger amount of hydroxyl groups per molecular chain of cellulose. Therefore, it is considered that more hydrogen bonds are formed between the molecules of cellulose, and the biological attachment film 10a tends to have high strength. The regenerated cellulose contained in the biological attachment film 10a may be uncrosslinked.

The receptor stimulating component 20 is typically a component that stimulates a receptor in a living body and causes some reaction in the living body. Receptor stimulation component 20 has, for example, 18 MPa ^1/2 or more 25 MPa ^1/2 or less of the SP value. In this case, since the receptor stimulating component 20 is difficult to dissolve in water and the hydrophobicity of the receptor stimulating component 20 is not too high, the receptor stimulating component 20 easily penetrates into the living body.

The receptor stimulating component 20 may be, for example, at least one of a cooling sensitizer and a warming sensitizer. Receptors for cooling and warming are abundant in the skin. For example, by attaching the biological attachment film 10a to the skin, at least one of the cooling sensation agent and the warming sensation agent permeates into the skin, and at least one of the cooling sensation and the warming sensation can be felt.

The receptor stimulating component 20 stimulates, for example, at least one of the TRPV1 and TRPM8 receptors. In the living body, the TRPV1 receptor can function as a warming sensor, and the TRPM8 receptor can function as a cooling sensor. Therefore, when the TRPV1 receptor is stimulated, a pseudo warm feeling is felt, and when the TRPM8 receptor is stimulated, a pseudo cold feeling is felt.

Regarding the receptor stimulating component 20, for example, as a cooling agent, menthol, menton, camphor, pregol, isopregol, cineole, cubebol, menthyl acetate, pregil acetate, isopregyl acetate, menthyl sartylate, pregil sulcylate, isopregyl sulcylate, 3- (l-mentoxy) propane-1,2-diol, 2-methyl-3- (l-mentoxy) propane-1,2-diol, 2- (l-mentoxy) ethane-1-ol, 3-( l-mentoxy) propan-1-ol, 4- (l-mentoxy) butane-1-ol, menthyl 3-hydroxybutanoate, menthyl glyoxylate, p-menthan-3,8-diol, 1- (2-hydroxy) -4-Methylcyclohexyl) ethaneone, menthyl lactate, mentunglyserin ketal, menthyl-2-pyrrolidone-5-carboxylate, monomentyl succinate, alkali metal salt of monomentyl succinate, alkaline soil of monomentyl succinate Metal salts, monomentyl glutarate, alkali metal salt of monomentyl glutarate, alkaline earth metal salt of monomentyl glutarate, N-[[5-methyl-2- (1-methylethyl) cyclohexyl] carbonyl] glycine , P-menthan-3-carboxylic acid glycerol ester, menthol propylene glycol carbonate, menthol ethylene glycol carbonate, p-mentan-2,3-diol, 2-isopropyl-N, 2,3-trimethylbutaneamide, N- Ethyl-p-menthan-3-carboxamide, 3- (p-mentan-3-carboxamide) ethyl acetate, N- (4-methoxyphenyl) -p-menthancarboxamide, N-ethyl-2,2-diisopropylbutaneamide, N-cyclopropyl-p-menthancarboxamide, N- (4-cyanomethylphenyl) -p-menthancarboxamide, N- (2-pyridine-2-yl) -3-p-menthancarboxamide, N- (2-hydroxy) Ethyl) -2-isoproyl-2,3-dimethylbutaneamide, N- (1,1-dimethyl-2-hydroxyethyl) -2,2-diethylbutaneamide, cyclopropanecarboxylic acid (2-isopropyl-5-methyl) Cyclohexyl) amide, N-ethyl-2,2-diisopropylbutaneamide, N- [4- (2-amino-2-oxoethyl) phenyl] -p-menthancarboxamide, 2- Compounds such as [(2-p-mentoxy) ethoxy] ethanol, 2,6-diethyl-5-isopropyl-2-methyltetrahydropyran, trans-4-tert-butylcyclohexanol, and these racemic and optically active substances, Sugar alcohols such as xylitol, erythritol, dextrose, and sorbitol, Japanese peppermint oil, peppermint oil, sparemint oil, or eucalyptus oil can be used. Among these, menthol or camphor is preferably used as a cooling sensation agent. Menthol and camphor are easily available and are used in a wide range of fields such as quasi-drugs.

Regarding the receptor stimulating component 20, for example, as a warming agent, vanillyl methyl ether, vanillyl ethyl ether, vanillyl propyl ether, vanillyl isopropyl ether, vanillyl butyl ether, vanillyl amyl ether, vanillyl isoamyl ether, vanilli Luhexyl ether, isovanillyl methyl ether, isovanylyl ethyl ether, isovanillyl propyl ether, isovanylyl isopropyl ether, isovanylyl butyl ether, isovanylyl amyl ether, isovanylyl isoamyl ether, isovanillyl hexyl ether, ethyl Vanillyl methyl ether, ethyl vanillyl ethyl ether, ethyl vanillyl propyl ether, ethyl vanillyl isopropyl ether, ethyl vanillyl butyl ether, ethyl vanillyl amyl ether, ethyl vanillyl isoamyl ether, ethyl vanillyl hexyl ether, vanillin propylene glycol acetal , Isovanillin propylene glycol acetal, ethyl vanillin propylene glycol acetal, vanillyl butyl ether acetate, isovanillyl butyl ether acetate, ethyl vanillyl butyl ether acetate, 4- (l-mentoxymethyl) -2- (3'-methoxy) -4'-Hydroxyphenyl) -1,3-dioxolane, 4- (l-mentoxymethyl) -2- (3'-hydroxy-4'-methoxyphenyl) -1,3-dioxolane, 4- (l-) Mentoxymethyl) -2- (3'-ethoxy-4'-hydroxyphenyl) -1,3-dioxolane, capsaicin, dihydrocapsaicin, nordihydrocapsaicin, homodihydrocapsaicin, homocapsaicin, biscapsaicin, trishomocapsicin, nor Norcapsaicin, norcapsaicin, capsaicinol, vanillylcaprilamide (octylate vanillylamide), vanillylperiragonamide (nonylate vanillylamide), vanillylcaproamide (decylate vanillylamide), vanillylundecaneamide (undecylate vanillylamide), N -Trans-ferroyltyramine, N-5- (4-hydroxy-3-methoxyphenyl) -2E, 4E-pentadieroyl piperidine, N-trans-ferloyl piperidine, N-5- (4-hydroxy-3-3) Methoxyphenyl) -2E-pentenoyl piperidine, N-5- (4-hydroxyphenyl) -2E, 4E-Pentazieroyl piperidine, piperin, isopiperin, chavicine, isochavicin, piperamine, piperetin, piperorain B, retrofractamide A, piperaside, gingerolside, piperiline, piperamide C5: 1 (2E), piperamide C7: 1 (6E), piperamide C7: 2 (2E, 6E), Piperamide C9: 1 (8E), Piperamide C9: 2 (2E, 8E), Piperamide C9: 3 (2E, 4E, 8E), Fagaramide, Sunshoal-I, Sunshoal-II , Hydroxysanshoal, Sanshoamide, Gingerol, Shogaol, Zingeron, Methylgingerol, Parador, Spirantol, Cavicin, Polygodial (Tadeonal), Isopolygodial, Dihydropolygodial, Tadeon, Togarashi fruit extract and these Ramemi and optically active substances, pepper oil, pepper ole olesin, ginger ole olesin, jumbu ole olesin (Kibana Dutch Sennichi extract), sun pepper extract, sun shoal-I, sun shoal-II, sun pepper amide, black Natural products such as pepper extract, white pepper extract, and tade extract can be used. Among these, vanillyl ether derivatives, capsaicin, or dihydrocapsaicin are preferably used as warming agents. These are materials that are often used for living organisms and are also often used as quasi-drugs.

The receptor stimulating component 20 is preferably at least one selected from the group consisting of menthol, camphor, vanillyl ether derivatives, capsaicin, and dihydrocapsaicin.

The content of the receptor stimulating component 20 in the biological attachment film 10a is not limited to a specific value. The content is, for example, 0.0001% or more and 50% or less on a weight basis. When the content is 0.0001% or more on a weight basis, it can stimulate the receptors of the living body and bring about a reaction such as a feeling of coldness or a feeling of warmth in the living body. In addition, when the content is 0.0001% or more on a weight basis, the receptor stimulating component 20 is used in the biological attachment film 10a by using liquid chromatography-mass spectrometry (LC-MS) or a spectrophotometer. Retention can be easily verified. On the other hand, when the content of the receptor stimulating component 20 in the biological attachment film 10a is 50% or less on a weight basis, the receptor stimulating component 20 can be easily retained in the biological attachment film 10a.

The content of the receptor stimulating component 20 in the film 10a for attaching to a living body is more preferably 0.01% or more on a weight basis. In this case, the content of the receptor stimulating component 20 in the biological attachment film 10a can be easily calculated by measuring the weight of the biological attachment film 10a or the like. In addition, the stimulation of the receptor in the living body by the receptor stimulating component 20 makes it easier to feel the reaction such as warmth and coldness.

Polymer M _SP20-30 so long as it has a 20 MPa ^1/2 or more 30 MPa ^1/2 or less of the SP value is not limited to a specific polymer. As the polymer M _SP20-30 , for example, _{polysaccharides} such as hydroxypropyl methyl cellulose, hydroxyethyl cellulose, methyl cellulose, ethyl cellulose, xanthan gum, starch, guar gum, cationized guar gum, hyaluronic acid, gelatin, polyglutamic acid, polyargic acid, polylysine, polyalanine. Polyamino acids such as proteins, polyvinyl alcohols, carboxyvinyl polymers, polyacrylic acid, methyl polyacrylate, ethyl polyacrylate, butyl polyacrylate, polyvinylpyrrolidone, poly-α-hydroxycarboxylic acid, poly-N-vinylacetamide , Polyacrylamide, artificial polymers such as polyamidine, polyvinylidene fluoride, acetyl cellulose, polyvinyl butyral, and nylon can be used.

The polymer M _SP20-30 is preferably at least one selected from the group consisting of polyvinylidene fluoride, acetyl cellulose, polyvinyl butyral, and nylon. Although these materials are insoluble in water, they have moderate hydrophilicity. Therefore, the speed at which the mounting liquid permeates the inside of the biological sticking membrane 10a and the speed at which the mounting liquid moves from the inside of the biological sticking membrane 10a to the outside of the biological sticking membrane 10a can be adjusted to a desired speed, and the receptor can be used. It is easy to continue the release of the stimulating component 20 for a long time.

The content of the polymer M _SP20-30 in the biological attachment film 10a is not limited to a specific value. Its content is, for example, 0.1% or more and 50% or less on a weight basis. When the content of the polymer M _SP20-30 in the bio-attached membrane 10a is 0.1% or more on a weight basis, the polymer M _SP20-30 can make it difficult for the mounting solution to permeate into the membrane in a short period of time. The release rate of the receptor stimulating component 20 is likely to be adjusted appropriately. On the other hand, _when the content of the polymer M _SP20-30 in the biological attachment film 10a is 50% or less on a weight basis, the polymer M _SP20-30 can be easily held in the biological attachment film 10a and can be attached. The polymer M _SP20-30 makes it difficult for the liquid to permeate appropriately, and the release rate of the receptor stimulating component 20 is likely to be adjusted appropriately.

The weight average molecular weight of the polymer M _SP20-30 is not limited to a specific value. The polymer M _SP20-30 has, for example, a weight average molecular weight of 100,000 or more and 2,000,000 or less. When the weight average molecular weight of the polymer M _SP20-30 is 100,000 or more, the polymers M _SP20-30 are likely to be entangled with each other. In addition, the polymer M _SP20-30 is likely to be retained in the structure 15 containing regenerated cellulose. Therefore, the release rate of the receptor stimulating component 20 is likely to be appropriately adjusted. When the weight average molecular weight of the polymer M _SP20-30 is 2,000,000 or less, the polymer M _SP20-30 is easily retained in the structure 15 containing regenerated cellulose and is excellent in processability.

As shown in FIG. 1, in the biological attachment film 10a, the structure 15 containing regenerated cellulose may be formed as a composite of regenerated cellulose and the polymer M _SP20-30 . The receptor stimulating component 20 may exist in a dispersed state in, for example, the biological attachment film 10a.

The average pore diameter in the biological attachment film 10a is not limited to a specific value. The biological attachment film 10a has, for example, an average pore diameter of 10 nm or less. In this case, the rate at which the mounting solution permeates the inside of the biological attachment film 10a is easily adjusted to a desired level, and the release rate of the receptor stimulating component 20 is easily adjusted appropriately. The average pore diameter of the film 10a for attaching to a living body is preferably 3.0 nm or less. In this case, the rate at which the mounting solution permeates the inside of the biological attachment film 10a is more likely to be adjusted to a desired level, and the release rate of the receptor stimulating component 20 is more likely to be adjusted more appropriately. The average pore diameter of the biological attachment film 10a can be determined, for example, based on the measurement results of the gas adsorption method using nitrogen.

When the biological attachment film 10a is viewed in a plan view, the shape of the biological attachment film 10a is not particularly limited. The biological attachment film 10a can be circular, elliptical, or polygonal in plan view. The film 10a for attaching to a living body may have an irregular shape in a plan view.

The biological attachment film 10a can be a self-supporting film. As used herein, the term "self-supporting membrane" means a membrane that can maintain its morphology without a support. For example, when the self-supporting membrane is lifted by pinching a part of the self-supporting membrane with a finger or tweezers, the self-supporting membrane is not damaged and the self-supporting membrane is not damaged. It is possible to lift the whole of. As shown in FIG. 1, the biological attachment film 10a has, for example, a first portion 11f and a second portion 11s. The first portion 11f is a planar portion that is in contact with the first main surface P1 and is located away from the second main surface P2 in the thickness direction of the biological attachment film 10a. The second part 11f is a planar part located between the first part 11f and the second main surface P2 in the thickness direction of the biological attachment film 10a. For example, in the biological attachment film 10a, the bulk density of the regenerated cellulose at the second site 11s is higher than the bulk density of the regenerated cellulose at the first site 11f. According to such a configuration, the first site 11f of the biological attachment film 10a tends to contain a desired amount of the receptor stimulating component 20. The biological attachment film 10a may have at least one site having a bulk density different from that of the first site 11f and the second site 11s, for example, a third site. The third site is arranged, for example, between the first main surface P1 and the first site 11f, between the first site 11f and the second site 11s, or between the second site 11s and the second main surface P2. sell.

The biological attachment film 10a is used by being attached to the skin or nails at parts such as the face and arms. The biological attachment film 10a typically has an area of 7 mm ² or more. As a result, a wide area can be covered when the biological attachment film 10a is attached to the skin. The biological attachment film 10a may be attached to the surface of a biological tissue other than the skin such as an organ. By attaching the biological attachment film 10a to the surface of the organ, healing of the organ can be promoted. In addition, adhesion between organs can be prevented.

Using the biological attachment film 10a, for example, the biological attachment sheet 50a shown in FIG. 3A can be provided. The biological attachment sheet 50a includes a biological attachment film 10a and a first protective layer 21. The first protective layer 21 is arranged on at least one of the first main surface P1 and the second main surface P2 of the biological attachment film 10a. The first protective layer 21 is removable from the biological attachment film 10a.

The second main surface P2 is, for example, a main surface that is exposed when the biological film 10a is used. The first protective layer 21 is arranged on, for example, the second main surface P2.

The first protective layer 21 is, for example, (i) polyethylene, polypropylene, polyethylene terephthalate, nylon, acrylic resin, polycarbonate, polyvinyl chloride, acrylonitrile-butadiene-styrene (ABS) resin, polyurethane, synthetic rubber, cellulose, Teflon (registered). It can be a sheet of polymer material such as (trademark), aramid, and polyimide, woven fabric, non-woven fabric, or mesh, (ii) sheet-like metal, or (iii) sheet-like glass. The entire or part of the surface of the first protective layer 21 may be chemically or physically surface-treated. The first protective layer 21 has the same or different shape as the biological sticking film 10a in a plan view, and has the same or different size as the biological sticking film 10a. For example, a plurality of biological attachment films 10a may be arranged on a single first protective layer 21. The shape of the biological attachment film 10a can be maintained without the first protective layer 21. Therefore, even if the first protective layer 21 is removed from the second main surface 12, the biological attachment film 10a can maintain its shape.

As shown in FIG. 3A, for example, the first main surface P1 of the biological attachment film 10a is brought close to the biological attachment sheet 50a toward a specific part (for example, skin) of the living body, and the first main surface of the biological attachment film 10a is brought close to it. The surface P1 is brought into contact with a specific part of the living body. At this time, the mounting agent may be supplied to a specific part of the living body or the film 10a for attaching to the living body. The mounting agent contains components such as water, fats and oils, alcohol, and emulsifiers. The mounting agent may contain a predetermined active ingredient. Next, as shown in FIG. 3B, the first protective layer 21 is peeled off from the second main surface P2 of the biological attachment film 10a. At this time, the biological attachment film 10a is in close contact with the biological tissue, and the state in which the biological attachment film 10a is attached to the biological tissue is maintained. When the first protective layer 21 is completely peeled off, as shown in FIG. 3C, the entire second main surface P2 of the biological attachment film 10a is exposed.

The biological attachment sheet 50a may be modified as the biological attachment sheet 50b shown in FIG. The biological attachment sheet 50b is configured in the same manner as the biological attachment sheet 50a, unless otherwise specified. The same reference numerals are given to the components of the biological attachment sheet 50b that are the same as or corresponding to the components of the biological attachment sheet 50a, and detailed description thereof will be omitted. The description of the biological attachment sheet 50a also applies to the biological attachment sheet 50b, as long as there is no technical contradiction.

As shown in FIG. 4, the biological attachment sheet 50b further includes a second protective layer 22. The second protective layer 22 is arranged on the first main surface P1. The first main surface P1 can be protected by the second protective layer 22. In addition, the second protective layer 22 facilitates handling of the biological attachment sheet 50b.

The material of the second protective layer 22 may be the same as the material of the first protective layer 21, or may be different from the material of the first protective layer 21. The second protective layer 22 has the same or different shape as the biological attachment film 10a in a plan view, and has the same or different size as the biological attachment film 10a. The second protective layer 22 has the same or different shape as the first protective layer 21 in a plan view, and has the same or different size as the first protective layer 21.

The second protective layer 22 is typically removable from the first main surface P1. When using the biological attachment sheet 50b, for example, first, the second protective layer 22 is peeled off from the biological attachment film 10a. As a result, the first main surface P1 is exposed. After that, the first main surface P1 is brought close to a specific part of the living body, and the living body attachment film 10a is attached to the specific part of the living body in the same manner as the method of using the living body attachment sheet 50a.

A kit including a biological attachment film 10a or a biological attachment sheet 50a and a mounting solution used for attaching the biological attachment film 10a to a living body may be provided. The biological attachment film 10a or the biological attachment sheet 50a and the mounting solution may be provided separately. The mounting solution may be provided in a predetermined container.

The components contained in the mounting solution are not limited to specific components as long as the biological attachment film 10a can be attached to the living body. Wetting solution contains, for example, a solvent having a 25 MPa ^1/2 or more 45 MPa ^1/2 or less of the SP value. In this case, the speed at which the mounting liquid permeates the inside of the biological sticking film 10a and the speed at which the mounting liquid moves from the inside of the biological sticking film 10a to the outside of the biological sticking film 10a are easily adjusted.

More specifically, the mounting solution contains at least one selected from the group consisting of, for example, water, ethanol, polyhydric alcohols, and dimethyl sulfoxide. The polyhydric alcohol is, for example, glycerin, propanediol, diglycerin, polyglycerin, 1,3-butanediol, or 1,4-butanediol. As a result, the speed at which the mounting liquid permeates the inside of the biological sticking film 10a and the speed at which the mounting liquid moves from the inside of the biological sticking film 10a to the outside of the biological sticking film 10a are adjusted to appropriate levels. Easy to be done. In addition, the polymer M _SP20-30 is gradually dissolved by the mounting solution, and the receptor stimulating component 20 is gradually released from the biological attachment membrane 10a. Therefore, it is easy to continue the release of the receptor stimulating component 20 for a long time, and the beauty effect is likely to be enhanced. In this case, the mounting liquid is, for example, water, an aqueous solution containing an inorganic salt such as a phosphate buffer, a liquid ethanol, an ethanol-containing liquid, a liquid polyhydric alcohol, a polyhydric alcohol-containing liquid, a liquid dimethyl sulfoxide, or a dimethyl sulfoxide. It can be a containing liquid, a beauty essence, a lotion, or a milky lotion.

A cosmetological method can be provided by using the film for attaching to a living body 10a. The beauty method includes, for example, attaching the biological attachment film 10a in a state where the first main surface P1 of the biological attachment film 10a is arranged between the second main surface P2 of the biological attachment film 10a and the biological tissue. .. In this case, the biological attachment film 10a may be attached according to the procedure shown in FIGS. 3A, 3B, and 3C. As described above, the speed at which the mounting liquid permeates the inside of the biological sticking film 10a and the speed at which the mounting liquid moves from the inside of the biological sticking film 10a to the outside of the biological sticking film 10a can be easily adjusted. Therefore, according to this cosmetological method, the release of the receptor stimulating component 20 is likely to be continued for a long time, and the cosmetological effect is likely to be enhanced.

In the cosmetological method, the mounting solution may be supplied onto the living body. In addition, the biological attachment film 10a may be arranged and attached on the living body while covering at least a part of the mounting liquid supplied on the living body. On the other hand, the order of the work of supplying the mounting liquid and the work of bringing the biological attachment film 10a closer to the biological tissue is not particularly limited. For example, the mounting solution may be dropped onto the biological attachment membrane 10a and the biological tissue while the biological attachment membrane 10a is in contact with the biological tissue.

The mounting solution preferably contains at least one selected from the group consisting of water, ethanol, polyhydric alcohols, and dimethyl sulfoxide. In this case, the biological attachment film 10a can be easily attached to the biological tissue. The polyhydric alcohol contained in the mounting solution is not limited to a specific polyhydric alcohol. The polyhydric alcohol contained in the mounting solution may be butanediol, propanediol, glycerin, propylene glycol, polyethylene glycol, diglycerin, polyglycerin, pentylene glycol, or dipropylene glycol. The mounting solution may contain at least one of glycerin and propanediol as a polyhydric alcohol. In this case, in this case, the biological attachment film 10a has high adhesion to the biological tissue, and the biological attachment film 10a can be attached to the biological tissue in a short time. The content of propanediol in the mounting solution is, for example, 5% by mass or more and 15% by mass or less. The content of glycerin in the mounting solution is, for example, 5% by mass or more and 10% by mass or less. When the mounting solution contains propanediol or glycerin in such a content, the adhesion of the biological attachment membrane 10a to the biological tissue is further improved, and the biological attachment membrane 10a is applied to the biological tissue in a shorter time. Can be installed. When the mounting solution contains water, ethanol, or polyhydric alcohol, the mounting solution is pure water, distilled water, physiological saline, lotion containing water, milky lotion containing water, beauty essence containing water, and It may be one selected from the group consisting of creams containing water.

The content of at least one selected from the group consisting of water, ethanol, polyhydric alcohols, and dimethyl sulfoxide in the mounting solution is not limited to a specific value. Its content is, for example, 1% by mass or more. As a result, the biological attachment film 10a can be easily attached to the biological tissue. Its content is preferably 10% or more. In this case, the biological attachment film 10a can be easily attached to the biological tissue. The mounting liquid may contain, for example, water, fat, alcohol, emulsifier, or the like, and may further contain other active ingredients described below.

The biological attachment film 10a may contain other active ingredients. Examples of other active ingredients are anti-wrinkle agents, moisturizers, whitening agents, UV blocking agents, anti-acne agents, hair care agents, body care agents, anti-sugar agents, hair restorers, cardiac stimulants, antipyretics, analgesics, vasodilators , Antianginal agents, asthma treatment agents, pesticides, insect repellents, deodorants, air fresheners, sanitary agents such as soaps and detergents, slow-release fertilizers, bactericides, antibacterial agents, etc.

Specific examples of active ingredients include glycerin, zeolite, retinol, hyaluronic acid, ceramide, collagen, amino acids, elastin, various extracts, citric acid, lecithin, carbomer, xanthan gum, dextran, palmitic acid, lauric acid, vaseline, titanium oxide, oxidation. Iron, phenoxyethanol, fullerene, astaxanthin, coenzyme, human oligopeptide, glycerin, diglycerin, sodium lactate, sorbitol, pyrrolidone carboxylic acid, amino acid polyglyceryl, polyglycerin, jojoba oil, trimethylglycine, mannitol, trehalose, glycosyl trehalose, purulan, erythritol , Elastin, dipropylene glycol, butylene glycol, ethyl ethylhexanoate, sodium acrylate, disodium edetate, sucrose amino acid ester, squalane, polyethylene glycol, polyoxyethylene hydrogenated castor oil, glycerin stearate, ethanol, polyvinyl alcohol, Vitamin A such as hydroxyethyl cellulose, ectin, retinol, retinal, retinoic acid, vitamin B such as thiamine, riboflavin, pyridoxin, pyridoxamine, folic acid, vitamin D such as ergocalciferol and cholecalciferol, vitamin E such as α-tocopherol, Vitamin represented by vitamin K of phylloquinone and menaquinone, vitamin A derivatives such as tretinoin and retinol palmitate, vitamin C derivatives such as glyceryl ascorbic acid, magnesium L-ascorbic acid-2-phosphate, ascorbic acid glucoside, α acetate -Vitamin E derivatives such as tocopherol, α-tocopheryl quinone, tocopheryl phosphate, tranexamic acid, arbutin, hydroquinone, kodiic acid, potassium 4-methoxysalicylate, lucinol, flavonols such as ellagic acid and gossipetin, mylicetin, rutin, and It can be an amino acid such as proline, phenylalanine, tryptophan, tyrosine, histidine and the like. Specific examples of active ingredients that are medical materials include isosorbide nitrate, indomethacin, diflucortron valerate, acyclovir, ketoconazole, ketoprofen, diclofenac sodium, dexamethasone propionic acid ester, felbinac, clobetazole propionic acid ester, loxoprofen, and methyl salicylate. , And tacrolimus. Specific examples of the active ingredients of pesticides or insect repellents include Ardent wettable powder, Actara granules, Ittetsu Proablel, Urara DF, Ortran wettable powder, Calphos emulsion, Kirap Proable, Grass-killing MIC, Colomite wettable powder, Sakidori EW, Thunderbolt 007, J-Ace wettable powder, Soileen, Tachigaren solution, Double stopper, Temacut proablel, Top gun flowable, Nativo flowable, Basagran solution, Perfect LX jumbo, Beerum granule, Fruit saver, Buiget It can be Fertella granules, Berkut flowables, Possible flowables, Motive emulsions, Movent flowables, Lymei flowables, Routine expert box granules, and Wide Attack SC.

The biological attachment film 10a may be modified as, for example, the biological attachment film 10b shown in FIG. The biological attachment film 10b is configured in the same manner as the biological attachment film 10a, unless otherwise specified. The components of the biological attachment film 10b corresponding to the components of the biological attachment film 10a are designated by the same reference numerals, and detailed description thereof will be omitted. The description of the biological attachment film 10a also applies to the biological attachment film 10b, unless technically inconsistent.

As shown in FIG. 2, in the biological attachment film 10b, for example, a mixture 25 of the receptor stimulating component 20 and the polymer M _SP20-30 is attached to the structure 15 containing regenerated cellulose. The mixture 25 may be present in a dispersed state on the biological attachment film 10b, or may be present in a continuous state on the biological attachment film 10b. In the mixture 25, the receptor stimulating component 20 may be encapsulated in the polymer M _SP20-30 , or at least a part of the receptor stimulating component 20 may be exposed.

An example of a method for manufacturing the biological attachment film 10a or the biological attachment film 10b will be described. First, a cellulose solution is prepared by dissolving cellulose in a solvent. In order to obtain a regenerated cellulose membrane having a weight average molecular weight of 100,000 or more, cellulose having a weight average molecular weight of at least 100,000 or more is used. As a result, a biological attachment film 10a having a thickness of 20 nm or more and 2000 nm or less can be produced. As described above, by increasing the weight average molecular weight of the cellulose used in the preparation of the cellulose solution, more hydroxyl groups are contained in the single molecular chain. As a result, many intermolecular hydrogen bonds can be formed, and a thinner film for attaching to a living body 10a or 10b can be stably produced. The cellulose used in the preparation of the cellulose solution is not particularly limited as long as it has a desired weight average molecular weight.

The cellulose used for preparing the cellulose solution may be either natural cellulose or regenerated cellulose. The cellulose used in the preparation of the cellulose solution can be, for example, cellulose derived from plants such as pulp and cotton, or cellulose produced by organisms such as bacteria. The impurity concentration in the raw material of cellulose is, for example, 20% by weight or less. If the weight average molecular weight of cellulose becomes too large, the viscosity of the solution becomes high and processing becomes difficult. Therefore, the weight average molecular weight of the regenerated cellulose in the finally obtained bioadhesive membrane 10a or bioadhesive membrane 10b is determined. It is preferably 2,000,000 or less, more preferably 1,000,000 or less, further preferably 500,000 or less, and most preferably 300,000 or less. Processing is possible if the weight average molecular weight is 2,000,000 or less, processing is easier if the weight average molecular weight is 1,000,000 or less, and further processing is performed if the weight average molecular weight is 500,000 or less. With a weight average molecular weight of 300,000 or less, a more stable sheet with little variation in thickness can be obtained.

The solvent is, for example, a solvent containing at least an ionic liquid (first solvent). By using the first solvent, cellulose can be dissolved in a relatively short time. 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. The ionic liquid contained in the first solvent is, for example, an ionic liquid containing an amino acid or an alkyl phosphate ester. Since the first solvent contains such an ionic liquid, it is possible to dissolve cellulose while suppressing a decrease in the molecular weight of cellulose.

Cellulose may be dissolved using an ionic liquid pre-diluted with a solvent that does not precipitate cellulose. For example, a mixture of an aprotic polar solvent and an ionic liquid may be used as the first solvent. Aprotic polar solvents are less likely to form hydrogen bonds and less likely to precipitate cellulose.

The ionic liquid contained in the first solvent is, for example, an ionic liquid represented by the following formula (II). In the ionic liquid represented by the formula (II), the anion is an amino acid. As described in formula (II), in this ionic liquid, the anion contains a terminal carboxyl group and a terminal amino group. The cation of the ionic liquid represented by the formula (II) can be a quaternary ammonium cation.

In formula (II), 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. The substituent may contain a branch in the carbon chain. The substituent may contain a functional group such as an amino group, a hydroxyl group, or a carboxyl group. n is, for example, 4 or 5.

The ionic liquid contained in the first solvent may be an ionic liquid represented by the following formula (III). In formula (III), R ₁ , R ₂ , R ₃ , and R ₄ independently represent an alkyl group having a hydrogen atom or 1 to 4 carbon atoms.

A second solvent may be further added in the step of preparing the cellulose solution. For example, the second solvent may be further added to the mixture of cellulose having a predetermined weight average molecular weight and the first solvent. The second solvent is, for example, a solvent that does not precipitate cellulose. The second solvent can be an aprotic polar solvent.

The concentration of cellulose in the cellulose solution is typically 0.2% by weight or more and 15% by weight or less. When the concentration of cellulose in the cellulose solution is 0.2% by weight or more, the bioadhesive film 10a or 10b has the strength necessary to maintain its shape while reducing the thickness of the bioadhesive film 10a or 10b. can get. Further, when the concentration of cellulose in the cellulose solution is 15% by weight or less, the precipitation of cellulose in the cellulose solution can be suppressed. The concentration of cellulose in the cellulose solution may be 1% by weight or more and 10% by weight or less. When the concentration of cellulose in the cellulose solution is 1% by weight or more, a bioadhesive film 10a or 10b having higher strength can be obtained. When the concentration of cellulose in the cellulose solution is 10% by weight or less, a stable cellulose solution in which the precipitation of cellulose is further reduced can be prepared. Further, the polymer M _SP20-30 or the receptor stimulating component 20 may be dissolved or dispersed in the cellulose solution. Alternatively, the polymer M _SP20-30 or the receptor stimulator may be first dissolved or dispersed in the first solvent or the second solvent, and then mixed with the cellulose solution to dissolve or disperse. Also, without using a solvent, is mixed with the cellulose solution by heating the polymer M _SP20-30 above the glass transition temperature of the polymer M _SP20-30, it may be used in the subsequent steps.

Next, a cellulose solution is applied to the surface of the substrate to form a liquid film on the surface of the substrate. The contact angle of the surface of the substrate with water is, for example, 95 ° or less. In this case, the wettability of the cellulose solution to the substrate is appropriate, and a liquid film spreading along the surface of the substrate can be stably formed. The material of the substrate is not particularly limited. The substrate typically has a non-porous structure with a smooth surface. In this case, it is possible to prevent the cellulose solution from entering the inside of the substrate, and it is easy to separate the biological attachment film 10a or 10b from the substrate in a subsequent step.

The substrate may be chemically or physically surface modified. As the substrate, for example, a substrate made of a polymer material that has undergone surface modification treatment such as ultraviolet (UV) irradiation or corona treatment may be used. The method of surface modification is not particularly limited. For example, surface modifier coating, surface modification, plasma treatment, sputtering, etching, or blasting may be applied.

The method of forming a liquid film of a cellulose solution on a substrate is, for example, a gap coating, a slot die coating, a spin coating, or a coating using a bar coater (Metering) that forms a predetermined gap between the substrate and the surface of the substrate by an applicator or the like. Rod coating) and gravure coating. The thickness of the liquid film adjusted by the thickness of the gap or the size of the opening of the slot die and the coating speed, the rotation speed of the spin coating, the depth of the groove of the bar coater or the gravure coating, the coating speed, etc., and the concentration of the cellulose solution. By adjusting, the thickness of the biological attachment film 10a or 10b can be adjusted. The method of forming a liquid film of the cellulose solution on the substrate may be a casting method, screen printing using a squeegee, spray coating, or electrostatic spraying.

When forming a liquid film of the cellulose solution on the substrate, at least one of the cellulose solution and the substrate may be heated. Heating of the cellulose solution may be carried out, for example, in a temperature range in which the cellulose solution can be kept stable (for example, 40 ° C. or higher and 100 ° C. or lower). The liquid film of the cellulose solution formed on the substrate may be heated. The heating of the liquid film may be performed, for example, at a temperature lower than the decomposition temperature of the ionic liquid contained in the first solvent (for example, 50 ° C. or higher and 200 ° C. or lower). By heating the liquid film at such a temperature, a solvent other than the ionic liquid (for example, a second solvent) can be appropriately removed, and the strength of the biological attachment film 10a or 10b tends to increase. The heating of the liquid film may be carried out in a reduced pressure environment. In this case, the solvent other than the ionic liquid can be appropriately removed in a shorter time at a temperature lower than the boiling point of the solvent.

After forming a liquid film of the cellulose solution on the substrate, the liquid film may be gelled. For example, by exposing the liquid film to vapor of a liquid that can be dissolved in an ionic liquid and does not dissolve cellulose, the liquid film can be gelled to obtain a polymer gel sheet. For example, if the liquid film is left in an environment with a relative humidity of 30% RH or more and 100% RH or less, the ionic liquid in the liquid film comes into contact with water, and the solubility of cellulose in the liquid film decreases. As a result, a part of the cellulose molecules is precipitated to form a three-dimensional structure. As a result, the liquid film gels. The presence or absence of a gel point can be determined by whether or not it is possible to lift the gelled film.

The heating of the liquid film may be performed before the gelation of the liquid film, after the gelation of the liquid film, or before and after the gelation of the liquid film. ..

Next, the substrate and the polymer gel sheet are immersed in a rinse solution which is a liquid that does not dissolve cellulose. In this step, the ionic liquid is removed from the polymeric gel sheet. This step can be understood as the step of cleaning the polymer gel sheet. In this step, in addition to the ionic liquid, a part of the components other than the cellulose and the ionic liquid (for example, the second solvent) may be removed from the components contained in the cellulose solution. The rinse solution is typically a liquid that is soluble in ionic liquids. Examples of such liquids are water, methanol, ethanol, propanol, butanol, octanol, toluene, xylene, acetone, acetonitrile, dimethylacetamide, dimethylformamide, and dimethyl sulfoxide.

Next, the polymer gel sheet may be immersed in a solution of the receptor stimulating component 20 and the polymer M _SP20-30 . In that case, the solvent in the solution of the receptor stimulating component 20 and the polymer M _SP20-30 is, for example, water, methanol, ethanol, propanol, butanediol, propanediol, propylene glycol, polyethylene glycol, diglycerin, pentylene. Glycol, dipropylene glycol butanol, acetone, glycerin, propanediol, 1,3-butanediol, 1,4-butanediol, diglycerin, polyethylene glycol, dimethicone, tetrahydrofuran (THF), dimethylsulfoxide, toluene, methyl acetate, acetic acid It may be at least one selected from the group consisting of ethyl, tetrachloroethylene, petroleum ether, acetonitrile, diethyl ether, methylene chloride, chloroform, NN-dimethylformamide, acetic acid, formic acid, hexane, and decane. When the receptor stimulating component 20 or the polymer M _SP20-30 is added to the cellulose solution, the polymer gel sheet may be immersed in the solution of the polymer M _SP20-30 or the solution of the receptor stimulating component 20. Good. _Instead of immersing the polymer gel sheet in a solution of the receptor stimulating component 20 and the polymer M _SP20-30 , the receptor stimulating component 20 may be attached to the polymer gel sheet by spraying, vapor deposition, or coating. Further, the polymer M _SP20-30 may be attached to the polymer gel sheet after the receptor stimulating component 20 is attached to the polymer gel sheet. The polymer gel sheet may be immersed in a solution, a dispersion, or an emulsion containing the above-mentioned active ingredient, separately from the immersion in the solution of the receptor stimulating component 20.

Next, unnecessary components such as a solvent are removed from the polymer gel sheet. In other words, the polymer gel sheet is dried. As a method for drying the polymer gel sheet, a drying method such as natural drying, vacuum drying, heat drying, freeze drying, and supercritical drying can be applied. The method for drying the polymer gel sheet may be vacuum heating. The conditions for drying the polymer gel sheet are not particularly limited. As the conditions for drying the polymer gel sheet, a time and temperature sufficient for removing the second solvent and the rinsing solution are selected. By removing the solvent from the polymer gel sheet, a biological attachment film 10a or 10b can be obtained.

When freeze-drying or supercritical drying is applied in the step of drying the polymer gel sheet, a porous structure bioadhesive film 10a having a lower bulk density is compared with the case where natural drying, vacuum drying, or heat drying is applied. Is easy to obtain. When the biological attachment film 10a has a porous structure, the mounting liquid is likely to be guided to the inside of the biological attachment film 10a when the biological attachment film 10a is attached to the living body. In the step of drying the polymer gel sheet, for example, when freeze-drying is applied, a solvent that can be frozen and has a boiling point of about 100 ° C. to 200 ° C. is used. For example, freeze-drying can be carried out using a solvent such as water, tert-butyl alcohol, acetic acid, 1,1,2,2,3,3,4-heptafluorocyclopentane, or dimethyl sulfoxide.

In the above method, the polymer gel sheet is immersed in a solution of the receptor stimulating component 20 and the polymer M _SP20-30 prior to the drying of the polymer gel sheet, but is received after the polymer gel sheet is dried. The step of adhering the body stimulating component 20 and the polymer M _SP20-30 may be performed. For example, the polymer sheet obtained by drying the polymer gel sheet may be immersed in the solution of the receptor stimulating component 20. Then, the polymer sheet after immersion is further dried. In this case as well, the receptor stimulating component 20 may be attached to the polymer sheet by a spraying method, thin film deposition, or coating.

The bioadhesive membrane of the present disclosure will be described in more detail by way of examples. The biological attachment film of the present disclosure is not limited to the following examples.

(Example 1)
A wood-based bleached pulp having a cellulose purity of 80% or more was prepared. The weight average molecular weight of cellulose contained in bleached pulp was measured by the Gel Permeation Chromatography (GPC) -Multi Angle Light Scattering (MALS) method and found to be about 230,000. For this measurement, a liquid feeding unit LC-20AD manufactured by Shimadzu Corporation was used, and a differential refractometer Optilab rEX manufactured by Wyatt Technology Corporation and a multi-angle light scattering detector DAWN HELEOS were used as detectors. TSKgel α-M manufactured by Tosoh Corporation was used as the column, and a dimethylacetamide solution of lithium chloride (lithium chloride concentration: 0.1 M) was used as the solvent. The measurement was performed under the conditions of column temperature: 23 ° C. and flow velocity: 0.8 mL / min.

The bleached pulp was dissolved in an ionic liquid to prepare a cellulose solution. Ethylmethylimidazolium diethyl phosphate was used as the ionic liquid. Further, a PVDF solution obtained by dissolving polyvinylidene fluoride (PVDF) having a weight average molecular weight of 180,000 and an SP value of 22.7 MPa ^1/2 in dimethylsulfoxide and a cellulose solution were mixed and PVDF- A cellulose solution was prepared. Next, a gap coating was applied to apply a PVDF-cellulose solution on the surface of the glass substrate to form a coating film on the glass substrate. At this time, the size of the gap in the gap coating was adjusted with the aim of achieving a thickness of the film for attaching to the living body according to Example 1. Then, the coating film was dried and washed to remove the ionic liquid from the coating film to obtain a polymer gel sheet.

Next, the polymer gel sheet was further immersed in an ethanol solution in which vanillyl butyl ether having an SP value of 23.1 MPa ^1/2 was dissolved. Then, the excess solution was wiped off, and the polymer gel sheet was dried to obtain a membrane for biological attachment according to Example 1. The content of vanillyl butyl ether in the film for attaching to the living body according to Example 1 was 0.1% by weight. This was confirmed by using a calibration curve from the absorbance of the spectrophotometer V-770 (JASCO Corporation) using a solution of vanillyl butyl ether extracted from the membrane for attaching to a living body with ethanol. Using a stylus-type profiling system (manufactured by Bruker Nano Incorporated, trade name: DEKTAK (registered trademark)), the thickness of the bioadhesive film according to Example 1 was measured. As a result, the thickness of the biological attachment film 10a according to Example 1 was about 410 nm. The thickness of the biological attachment film according to Example 1 was determined by measuring the thickness of the biological attachment film at a plurality of locations and averaging them. The concentration of PVDF in the bio-sticking membrane according to Example 1 was determined based on the weight of the extract obtained by extracting PVDF from the bio-sticking membrane using dimethyl sulfoxide and drying it. As a result, the concentration of PVDF in the film for attaching to the living body according to Example 1 was 5.1% by weight.

Using BELSORP-mini II manufactured by Microtrac Bell Co., Ltd., the average pore size of the membrane for bioattachment according to Example 1 was measured, and the measurement results were analyzed according to the BET method. As a result, the average pore diameter of the bioadhesive film according to Example 1 was 2.8 nm.

(Example 2)
As shown in Table 1, a membrane for bioattachment according to Example 2 was obtained in the same manner as in Example 1 except that the concentration of PVDF was changed. The concentration of vanillyl butyl ether in the film for attaching to the living body according to Example 2 was 0.1% by weight. In addition, the concentration of PVDF in the film for attaching to the living body according to Example 2 was 10.3% by weight. The thickness of the film for attaching to the living body according to Example 2 was about 380 nm. The thickness of the film for attaching to the living body according to Example 2 was determined in the same manner as in Example 1.

(Example 3)
As shown in Table 1, a membrane for attaching to a living body according to Example 3 was obtained in the same manner as in Example 1 except that the concentration of PVDF was changed. The concentration of vanillyl butyl ether in the film for attaching to the living body according to Example 3 was 0.1% by weight. In addition, the concentration of PVDF in the film for attaching to the living body according to Example 3 was 20.3% by weight. The thickness of the film for attaching to the living body according to Example 3 was about 360 nm. The thickness of the film for attaching to the living body according to Example 3 was determined in the same manner as in Example 1.

(Example 4)
Examples except that the PVDF solution and the cellulose solution were not mixed and the polymer gel sheet was immersed in a solution in which vanillyl butyl ether and PVDF were dissolved in dimethyl sulfoxide instead of an ethanol solution in which vanillyl butyl ether was dissolved. In the same manner as in No. 1, a bioadhesive film according to Example 4 was obtained. The concentration of vanillyl butyl ether in the film for attaching to the living body according to Example 4 was 0.1% by weight. The concentration of PVDF in the film for attaching to the living body according to Example 4 was 9.8% by weight. The thickness of the film for attaching to the living body according to Example 4 was about 370 nm. The thickness of the film for attaching to the living body according to Example 4 was determined in the same manner as in Example 1.

(Example 5)
The bioadhesive membrane according to Example 5 was obtained in the same manner as in Example 1 except that acetyl cellulose (SP value: 23.8 MPa ^1/2 , weight average molecular weight: 120,000) was used instead of PVDF. It was. The concentration of vanillyl butyl ether in the film for attaching to the living body according to Example 5 was 0.1% by weight. The concentration of acetyl cellulose in the film for attaching to the living body according to Example 5 was 9.6% by weight. The thickness of the film for attaching to the living body according to Example 5 was about 380 nm. The thickness of the film for attaching to the living body according to Example 5 was determined in the same manner as in Example 1.

(Example 6)
A bioadhesive film according to Example 6 was obtained in the same manner as in Example 1 except that nylon (SP value: 24.8 MPa ^1/2 , weight average molecular weight: 100,000) was used instead of PVDF. .. The concentration of vanillyl butyl ether in the film for attaching to the living body according to Example 6 was 0.1% by weight. The concentration of nylon in the film for attaching to the living body according to Example 6 was 9.1% by weight. The thickness of the film for attaching to the living body according to Example 6 was about 350 nm. The thickness of the film for attaching to the living body according to Example 6 was determined in the same manner as in Example 1.

(Example 7)
A bioadhesive film according to Example 7 was obtained in the same manner as in Example 1 except that polyvinyl butyral (SP value: 25.8 MPa ^1/2 , weight average molecular weight: 80,000) was used instead of PVDF. It was. The concentration of vanillyl butyl ether in the film for attaching to the living body according to Example 7 was 0.1% by weight. The concentration of polyvinyl butyral in the film for attaching to the living body according to Example 7 was 9.5% by weight. The thickness of the film for attaching to the living body according to Example 7 was about 380 nm. The thickness of the film for attaching to the living body according to Example 7 was determined in the same manner as in Example 1.

(Example 8)
A bioadhesive film according to Example 8 was obtained in the same manner as in Example 1 except that d-camphor (SP value: 21.2 MPa ^1/2 ) was used instead of vanillyl butyl ether. The concentration of d-camphor in the film for attaching to the living body according to Example 8 was 0.1% by weight. The concentration of d-camphor was determined by extracting d-camphor with ethanol and titrating with acetic anhydride. The concentration of PVDF in the film for attaching to the living body according to Example 8 was 10.3% by weight. The thickness of the film for attaching to the living body according to Example 8 was about 410 nm. The thickness of the film for attaching to the living body according to Example 8 was determined in the same manner as in Example 1.

(Example 9)
A bioadhesive film according to Example 9 was obtained in the same manner as in Example 1 except that L-menthol (SP value: 18.9 MPa ^1/2 ) was used instead of vanillyl butyl ether. The concentration of L-menthol in the film for attaching to the living body according to Example 9 was 0.1% by weight. This was determined by extracting L-menthol with ethanol and titrating with acetic anhydride. The concentration of PVDF in the film for attaching to the living body according to Example 9 was 10.3% by weight. The thickness of the film for attaching to the living body according to Example 9 was about 370 nm. The thickness of the film for attaching to the living body according to Example 9 was determined in the same manner as in Example 1.

(Example 10)
A film for bioattachment according to Example 10 was obtained in the same manner as in Example 1 except that capsaicin (SP value: 20.8 MPa ^1/2 ) was used instead of vanillyl butyl ether. The concentration of capsaicin in the film for attaching to the living body according to Example 10 was 0.1% by weight. This concentration was determined in the same manner as in Example 1. The concentration of PVDF in the film for attaching to the living body according to Example 10 was 10.3% by weight. The thickness of the film for attaching to the living body according to Example 10 was about 390 nm. The thickness of the film for attaching to the living body according to Example 10 was determined in the same manner as in Example 1.

(Comparative Example 1)
A film for bioattachment according to Comparative Example 1 was obtained in the same manner as in Example 1 except that the PVDF solution was not used. The concentration of vanillyl butyl ether in the film for attaching to the living body according to Comparative Example 1 was 0.1% by weight. The thickness of the film for attaching to the living body according to Comparative Example 1 was about 350 nm. The thickness of the film for attaching to the living body according to Comparative Example 1 was determined in the same manner as in Example 1.

(Comparative Example 2)
A film for bioattachment according to Comparative Example 2 was obtained in the same manner as in Example 1 except that polyethylene (SP value: 15.8 MPa ^1/2 , weight average molecular weight: 100,000) was used instead of PVDF. .. The concentration of vanillyl butyl ether in the film for attaching to the living body according to Comparative Example 2 was 0.1% by weight. Further, the concentration of polyethylene in the film for attaching to a living body according to Comparative Example 2 was 10.6% by weight. The thickness of the film for attaching to the living body according to Comparative Example 2 was about 410 nm. The thickness of the film for attaching to the living body according to Comparative Example 2 was determined in the same manner as in Example 1.

<Evaluation of time to feel warm or cold>
A mounting solution was prepared by mixing glycerin, propanediol, and ultrapure water. The concentrations of glycerin, propanediol, and ultrapure water in the mounting solution were 10% by mass, 5% by mass, and 85% by mass, respectively. The wearing solution is applied to the skin of the subject, and the biological attachment film according to Examples 1 to 10 and the biological attachment film according to Comparative Example 1 are attached to the skin, and then it is regularly checked whether a feeling of warmth or coldness is felt. I looked it up. The results are shown in Table 1. A represents a case where a feeling of coldness or warmth is felt, B represents a case where a feeling of coldness and warmth is slightly felt, and X represents a case where a feeling of coldness and warmth is hardly felt or not at all.

As shown in Table 1, when Examples 1 to 10 and Comparative Example 1 are compared, the biological film for attaching to the living body according to Examples 1 to 10 gives the subject both a warm feeling and a cold feeling even after 30 minutes have passed after wearing. I was able to do it. On the other hand, the bio-attached membranes according to Comparative Examples 1 and 2 could not give a warm feeling to the subject 30 minutes after wearing. It was suggested that the membranes for bioattachment according to Examples 1 to 10 continued to release the receptor stimulating component for a longer period of time than the membranes for bioattachment according to Comparative Example 1.

10a, 10b biological sticking film 11f first section 11s the second portion 15 structure 20 receptor stimulation component 50a including regenerated cellulose, 50b biological sticking sheet M _SP20-30 20MPa ^1/2 or 30 MPa ^1/2 or less of the SP value Polymer with P1 first main surface P2 second main surface

Claims (21)

Has a structure containing regenerated cellulose
A polymer having 20 MPa ^1/2 or more 30 MPa ^1/2 or less of the SP value, contains a receptor stimulation component,
It has a thickness of 20 nm or more and 2000 nm or less.
Membrane for biological attachment. The bioadhesive membrane according to claim 1, wherein the regenerated cellulose has a weight average molecular weight of 100,000 or more. The receptor stimulation component has a 18 MPa ^1/2 or more 25 MPa ^1/2 or less of the SP value, biological sticking layer according to claim 1 or 2. The membrane for biological attachment according to any one of claims 1 to 3, wherein the receptor stimulating component is at least one of a cooling sensitizer and a warming sensitizer. The biological attachment membrane according to any one of claims 1 to 4, wherein the receptor stimulating component stimulates at least one of the TRPV1 receptor and the TRPM8 receptor. The bioadhesive component according to any one of claims 1 to 5, wherein the receptor stimulating component is at least one selected from the group consisting of menthol, camphor, vanillyl ether derivative, capsaicin, and dihydrocapsaicin. film. The biological attachment membrane according to any one of claims 1 to 6, wherein the content of the receptor stimulating component in the biological attachment membrane is 0.0001% or more and 50% or less on a weight basis. The bioadhesive membrane according to any one of claims 1 to 7, wherein the polymer is at least one selected from the group consisting of polyvinylidene fluoride, acetyl cellulose, polyvinyl butyral, and nylon. The bio-sticking film according to any one of claims 1 to 8, wherein the content of the polymer in the bio-sticking film is 0.1% or more and 50% or less on a weight basis. The bioadhesive membrane according to any one of claims 1 to 9, wherein the polymer has a weight average molecular weight of 100,000 or more and 2,000,000 or less. The film for biological application according to any one of claims 1 to 10, which has an average pore diameter of 10 nm or less. The biological attachment film is a self-supporting film, and is
The bio-sticking film is located at least between the first main surface of the bio-sticking film and the second main surface located on the opposite side of the first main surface in the thickness direction of the bio-sticking film. Includes a planar first site and a planar second site located between the first site and the second main surface in the thickness direction of the biological attachment film.
The bulk density of the regenerated cellulose at the second site is higher than the bulk density of the regenerated cellulose at the first site.
The film for attaching to a living body according to any one of claims 1 to 11. The film for attaching to a living body according to any one of claims 1 to 12.
A first protective layer arranged on at least one of the first main surface and the second main surface of the biological attachment film and provided with a removable first protective layer.
Sheet for attaching to a living body. The second main surface is a main surface that is exposed when the biological film is used.
The biological attachment sheet according to claim 13, wherein the first protective layer is arranged on the second main surface. The biological attachment sheet according to claim 14, further comprising a second protective layer arranged on the first main surface. The biological attachment film according to any one of claims 1 to 12 or the biological attachment sheet according to any one of claims 13 to 15.
A mounting solution used for sticking the living body sticking film to the living body.
kit. The wetting solution may contain a solvent having 25 MPa ^1/2 or more 45 MPa ^1/2 or less of the SP value, kit of claim 16. The kit according to claim 16 or 17, wherein the mounting solution contains at least one selected from the group consisting of water, ethanol, polyhydric alcohols, and dimethyl sulfoxide. The biological attachment membrane is placed in a state where the first main surface of the biological attachment membrane according to any one of claims 1 to 12 is arranged between the second main surface of the biological attachment membrane and the biological tissue. Beauty methods, including pasting. Supplying the mounting solution onto the living body and
The bioadhesive film is arranged and affixed on the living body while covering at least a part of the mounting solution.
The beauty method according to claim 19. The cosmetological method according to claim 20, wherein the mounting solution contains at least one selected from the group consisting of water, ethanol, polyhydric alcohol, and dimethyl sulfoxide.

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