阅读说明：本技术 生物体贴附用膜及贴附生物体贴附用膜的美容方法 (Biological adhesion film and cosmetic method for adhering biological adhesion film ) 是由 川岛知子 谷池优子 波潟佑纪 青木贵裕 于 2019-02-07 设计创作，主要内容包括：本公开提供包含再生纤维素,并且对于缩短向生物体组织的佩戴所需要的时间而言有利的生物体贴附用膜。本公开的生物体贴附用膜(10)包含再生纤维素和促进剂。促进剂促进再生纤维素向生物体组织的佩戴。生物体贴附用膜(10)为具有20～5000nm的厚度的自支持型。促进剂由下述式(A)表示。式中,a和c为0以上的整数,b和d为1以上的整数,R<Sub>1</Sub>为氢原子、酰基、或烷基,R<Sub>2</Sub>为氢原子、羟基、酰基、或烷基。<Image he="364" wi="682" file="DDA0002666626620000011.GIF" imgContent="drawing" imgFormat="GIF" orientation="portrait" inline="no"></Image>(The present disclosure provides a film for biological application, which contains regenerated cellulose and is advantageous in shortening the time required to wear the film to a biological tissue. The disclosed film (10) for biological application contains regenerated cellulose and an accelerator. The promoter promotes the wearing of regenerated cellulose to the body tissue. The film (10) for biological adhesion is a self-supporting film having a thickness of 20 to 5000 nm. The accelerator is represented by the following formula (a). Wherein a and c are integers of 0 or more, b and d are integers of 1 or more, and R is 1 Is a hydrogen atom, an acyl group, or an alkyl group, R 2 Is a hydrogen atom, a hydroxyl group, an acyl group, or an alkyl group.)

1. A film for biological application, comprising regenerated cellulose and an enhancer, wherein the enhancer enhances wearing of the regenerated cellulose to a biological tissue,

the film for organism adhesion is a self-supporting type having a thickness of 20 to 5000nm,

the accelerator is represented by the following formula (A),

wherein a and c are integers of 0 or more, b and d are integers of 1 or more, and R is₁Is a hydrogen atom, an acyl group, or an alkyl group, R₂Is a hydrogen atom, a hydroxyl group, an acyl group, or an alkyl group.

2. The film for biological application according to claim 1, wherein the regenerated cellulose has a weight average molecular weight of 30,000 or more.

3. The film for biological adhesion according to claim 1 or 2, which has a thickness of 20 to 1300 nm.

4. The film for biological application according to any one of claims 1 to 3, wherein the regenerated cellulose has a weight average molecular weight of 150,000 or more.

5. The film for biological application according to any one of claims 1 to 4, wherein the content of the promoter in the film for biological application is 10 to 90% by weight.

6. The film for biological patch according to any one of claims 1 to 5, wherein the accelerator is at least 1 selected from the group consisting of a 2-or more-membered polyhydric alcohol, polyglycerol, glycerol fatty acid ester, and polyglycerol fatty acid ester.

7. The film for biological patch according to claim 6, wherein the accelerator is at least 1 selected from the group consisting of glycerin, polyglycerin, glyceryl monocaprylate, glyceryl monomyristate, polyglycerin caprylate, and polyglycerin myristate.

8. A cosmetic method for attaching a film for organism adhesion,

the film for biological adhesion contains regenerated cellulose and an accelerant, is self-supporting with a thickness of 20-5000 nm, promotes wearing of the regenerated cellulose to biological tissues, and is represented by the following formula (A),

in the cosmetic method, a wearing agent containing water is attached to a living tissue and the biological adhesion film, and the biological adhesion film is attached to the living tissue,

wherein a and c are integers of 0 or more, b and d are integers of 1 or more, and R is₁Is a hydrogen atom, an acyl group, or an alkyl group, R₂Is a hydrogen atom, a hydroxyl group, an acyl group, or an alkyl group.

9. The cosmetic method according to claim 8, said wearing agent containing a polyol.

Technical Field

The present disclosure relates to a biological adhesion film and a cosmetic method of adhering the biological adhesion film.

Background

Conventionally, a biological adhesive film to be adhered to a living tissue such as skin is known.

For example, patent document 1 describes a cosmetic method having an excellent effect of reducing so-called secondary adhesion, in which a cosmetic material such as foundation containing a large amount of a coloring material such as a pigment is not attached to clothes or the like, and also describes a film used in the cosmetic method. The film is composed of a base material film and a support, wherein the base material film has a thickness of 10-500 nm. In the cosmetic method described in patent document 1, a base film is attached to the skin, and the support of the attached film is removed. The material of the substrate film is polylactic acid and other materials. The substrate film carries components such as hyaluronic acid.

Disclosure of Invention

Problems to be solved by the invention

In the technique described in patent document 1, no study has been made on a biological adhesion film containing regenerated cellulose. Accordingly, the present disclosure provides a film for biological application that contains regenerated cellulose and is advantageous in reducing the time required to be worn on a biological tissue.

Means for solving the problems

Disclosed is a film for biological adhesion, which comprises a regenerated cellulose and an accelerating agent for accelerating the wearing of the regenerated cellulose to a biological tissue,

the film for biological adhesion is a self-supporting film having a thickness of 20 to 5000nm,

the accelerator is represented by the following formula (a).

[ wherein a and c are integers of 0 or more, b and d are integers of 1 or more, and R is₁Is a hydrogen atom, an acyl group, or an alkyl group, R₂Is a hydrogen atom, a hydroxyl group, an acyl group, or an alkyl group.]

Additional effects and advantages of the disclosed embodiments will be apparent from the description and drawings. Effects and/or advantages are provided according to various embodiments or features disclosed in the specification and the drawings, respectively, and not all of the various embodiments or features are required to obtain more than 1 of the effects and/or advantages.

ADVANTAGEOUS EFFECTS OF INVENTION

The above-mentioned membrane for biological application contains regenerated cellulose, and is advantageous in shortening the time required for wearing the membrane on a living tissue.

Drawings

Fig. 1 is a sectional view schematically showing an example of the laminate of the present disclosure.

Fig. 2A is a diagram showing a method of using the biological adhesion film of the present disclosure.

Fig. 2B is a diagram showing a method of using the biological patch film of the present disclosure.

Fig. 2C is a diagram showing a method of using the biological adhesion film of the present disclosure.

Fig. 3 is a sectional view schematically showing another example of the laminate of the present disclosure.

Detailed Description

(knowledge forming the basis of the present disclosure)

As described in patent document 1, polylactic acid is known as a material for a film to be adhered to a living tissue such as skin. However, polylactic acid is hydrophobic, and thus, it is considered that there is a possibility that a problem such as stuffiness may occur, and it is not necessarily appropriate to adhere a film of polylactic acid to a living tissue for a long period of time. On the other hand, cellulose films tend to have high water vapor transmission rates and to transmit moisture such as sweat. Therefore, when the cellulose film is attached to the skin, discomfort due to a problem such as stuffiness can be reduced.

The present inventors have developed a self-supporting biological adhesive film having a thickness of several μm or less, which is made of regenerated cellulose and has not been realized in the past. The present inventors have further studied this film for biological adhesion, and as a result, have found that there is room for shortening the time required for wearing the film on a living tissue. Therefore, the present inventors have repeatedly conducted many experiments in order to shorten the time required for wearing the biological adhesion film on the biological tissue. As a result, it has been newly found that: by including a predetermined component in the biological adhesion membrane containing regenerated cellulose, the time required for wearing the membrane to a biological tissue can be shortened. The present inventors have devised a biological adhesive film according to the present disclosure based on this new knowledge.

The outline of the scheme according to the present disclosure is as follows.

(item 1)

A film for biological adhesion, which comprises regenerated cellulose and an accelerating agent for accelerating the wearing of the regenerated cellulose to a biological tissue,

the film for biological adhesion is a self-supporting film having a thickness of 20 to 5000nm,

the accelerator is represented by the following formula (a).

[ wherein a and c are integers of 0 or more, b and d are integers of 1 or more, and R is₁Is a hydrogen atom, an acyl group, or an alkyl group, R₂Is a hydrogen atom, a hydroxyl group, an acyl group, or an alkyl group.]

(item 2)

The film for biological adhesion according to item 1, wherein the regenerated cellulose has a weight average molecular weight of 30,000 or more.

(item 3)

The film for biological adhesion according to item 1 or 2, which has a thickness of 20 to 1300 nm.

(item 4)

The film for biological adhesion according to any one of items 1 to 3, wherein the regenerated cellulose has a weight average molecular weight of 150,000 or more.

(item 5)

The film for biological application according to any one of items 1 to 4, wherein the content of the promoter in the film for biological application is 10 to 90% by weight.

(item 6)

The film for biological application according to any one of items 1 to 5, wherein the accelerator is at least 1 selected from the group consisting of a 2-membered or higher polyhydric alcohol, polyglycerol, glycerol fatty acid ester, and polyglycerol fatty acid ester.

(item 7)

The film for biological adhesion according to item 6, wherein the accelerator is at least 1 selected from the group consisting of glycerol, polyglycerol, glycerol monocaprylate, glycerol monomyristate, polyglycerol caprylate, and polyglycerol myristate.

(item 8)

A cosmetic method for attaching a film for organism adhesion,

the biological patch film is a self-supporting film comprising regenerated cellulose and an accelerant, and having a thickness of 20 to 5000nm, wherein the accelerant promotes wearing of the regenerated cellulose on a biological tissue, and is represented by the following formula (A),

in the cosmetic method, a wearing agent containing water is attached to a living tissue and the biological adhesion film, and the biological adhesion film is adhered to the living tissue.

[ wherein a and c are integers of 0 or more, b and d are integers of 1 or more, and R is₁Is a hydrogen atom, an acyl group, or an alkyl group, R₂Is a hydrogen atom, a hydroxyl group, an acyl group, or an alkyl group.]

(item 9)

The cosmetic method according to item 8, wherein the wearing preparation contains a polyhydric alcohol.

(embodiment mode)

Hereinafter, embodiments of the present disclosure will be described with reference to the drawings. The following embodiments are merely illustrative, and the biological adhesion film and the method of adhering the biological adhesion film of the present disclosure are not limited to the following embodiments. The numerical values, shapes, materials, constituent elements, arrangement and connection forms of the constituent elements, and the order of steps and steps shown in the following embodiments are examples, and are not described in a manner limiting the gist of the present disclosure. The following embodiments can be combined with each other as long as no contradiction occurs. Among the components in the following embodiments, components not described in the independent claims indicating the uppermost concept should be understood as not being essential. In the following description, components having substantially the same function are denoted by common reference numerals, and description thereof may be omitted. In order to avoid the drawings from becoming excessively complicated, some elements may not be illustrated.

The biological patch film 10 shown in fig. 1 contains regenerated cellulose and an accelerator. The promoter promotes the wearing of regenerated cellulose to the body tissue. The regenerated cellulose typically forms a skeleton (base material) of the biological patch film 10. The biological adhesion film 10 is a self-supporting film having a thickness of 20 to 5000 nm. In the present specification, the term "self-supporting membrane" refers to a membrane that can maintain the form of the membrane without a support. For example, when the self-supporting film is lifted by sandwiching a part of the self-supporting film with a finger or tweezers, the whole self-supporting film can be lifted without a support without damaging the self-supporting film. The accelerator is represented by the following formula (a).

[ wherein a and c are integers of 0 or more, b and d are integers of 1 or more, and R is₁Is a hydrogen atom, an acyl group, or an alkyl group, R₂Is a hydrogen atom, a hydroxyl group, an acyl group, or an alkyl group.]

The accelerator has, for example, free hydroxyl groups bound to the carbon chain. In addition, regenerated cellulose is rich in hydroxyl groups. Therefore, when a wearing agent containing water as described later is interposed between the biological adhesion film 10 and the biological tissue for wearing the biological adhesion film 10, the accelerating agent causes an interaction such as a hydrogen bond with both the regenerated cellulose and the wearing agent due to the hydroxyl group or the like as described above. Further, the accelerators may be capable of interacting with each other by hydrogen bonding or the like via hydroxyl groups or the like. As a result, the promoter promotes the wearing of regenerated cellulose to the living tissue. It is considered that the enhancer hardly interacts with a film exhibiting high hydrophobicity such as a film of polylactic acid, and it is difficult to facilitate wearing of the film exhibiting high hydrophobicity to a living tissue.

In the formula (A), a and c are, for example, 0 to 5, b is, for example, 1 to 10, and d is, for example, 1 to 100. Thus, the accelerating agent has favorable hydrophilicity from the viewpoint of accelerating the wearing of regenerated cellulose to living tissues. As a result, the wearing of the regenerated cellulose to the living tissue is promoted more reliably. In the formula (A), a, b and c may be 1, and d may be 100 or less. In this case, the accelerating agent has more favorable hydrophilicity from the viewpoint of accelerating the wearing of regenerated cellulose to living tissues.

In the formula (A), in R₁Or R₂In the case of an acyl group, the acyl group may contain a molecular chain containing a carbon atom such as a hydrocarbon chain or a (poly) ethylene glycol chain. When the acyl group is composed of an alkyl chain or an alkyl group containing a carbon atom, the length of the molecular chain is not particularly limited. The molecular chain is composed of, for example, 1 to 30 atoms. Substances having such molecular chains are often present in living bodies as substances such as sebum. Even if R of the accelerator₁Or R₂Is liberated from the promoter by hydrolysis, by R₁Or R₂The fatty acid produced by the dissociation of (a) is also easily biocompatible and is not easily harmful to the living body. The molecular chain is composed of, for example, 1 to 14 atoms. In this case, the enhancer has good hydrophilicity, and the biological adhesion membrane 10 can be easily worn on the biological tissue. In addition, the hydrocarbon chain in the acyl group may be any of a saturated hydrocarbon chain and an unsaturated hydrocarbon chain. When the acyl group is composed of a molecular chain containing a (poly) ethylene glycol chain, the length of the molecular chain is not particularly limited. The molecular chain is composed of, for example, 1 to 100 atoms. In the case of 100 or less, the viscosity is low and therefore the stickiness is small, and as described later, the stickiness of the biological adhesive film 10 is suppressed, which is advantageous from the viewpoint of ease of handling of the biological adhesive film 10.

The accelerator is, for example, at least 1 selected from the group consisting of 2-or more-membered polyhydric alcohol, polyglycerol, glycerol fatty acid ester, and polyglycerol fatty acid ester. Examples of the 2-or more-membered polyhydric alcohol include ethylene glycol, propylene glycol, butylene glycol, pentylene glycol, hexylene glycol, heptylene glycol, octylene glycol, glycerol, erythritol, threitol, arabitol, xylitol, ribitol, and the like,Iditol, galactitol, glucitol, mannitol, heptanol, mannoheptitol, butanetriol, heptatriol, heptatetiol, pentatriol, pentanetriol, hexanetriol, hexanetetrol, hexanpentol, heptanetriol, heptatetriol, heptanetriol, or heptahexaol. The polyglycerol can be diglycerol. The glycerin fatty acid ester is, for example, caprylic glyceride, lauric glyceride, palmitic glyceride, linoleic glyceride, stearic glyceride, oleic glyceride, behenic glycerideAcid esters, or glyceryl myristate. The polyglycerin fatty acid ester may be, for example, polyglycerin caprylate, polyglycerin laurate, polyglycerin palmitate, polyglycerin linoleate, polyglycerin stearate, polyglycerin oleate, polyglycerin behenateAcid esters, or polyglycerol myristate.

The accelerator may be at least 1 selected from the group consisting of glycerin, polyglycerin, glyceryl monocaprylate, glyceryl monomyristate, polyglycerin caprylate, and polyglycerin myristate. In this case, the interaction between the accelerating agent, the regenerated cellulose and the wearing agent is in a favorable state, and the regenerated cellulose is more easily worn on the living tissue. If the accelerator is polyglycerol, polyglycerol octanoate, or polyglycerol myristate, it is considered that the number of hydroxyl groups in 1 molecule of the accelerator is large, and the accelerator is more likely to properly interact with regenerated cellulose.

The content of the promoter in the biological patch film 10 is, for example, 10 to 90 wt%. If the content of the promoter in the biological adhesion film 10 is 10% by weight or more, it is advantageous from the viewpoint of promoting the wearing of the biological adhesion film 10 on the biological tissue. If the content of the accelerator in the biological adhesion film 10 is 90 wt% or less, the stickiness of the biological adhesion film 10 is suppressed, which is advantageous from the viewpoint of ease of handling of the biological adhesion film 10. The content of the accelerator in the biological patch film 10 may be 15 to 50 wt%. If the content of the promoter in the biological adhesion film 10 is 15% by weight or more, it is more advantageous from the viewpoint of promoting the wearing of the biological adhesion film 10 on the biological tissue. If the content of the accelerator in the biological adhesion film 10 is 90 wt% or less, the stickiness of the biological adhesion film 10 is further suppressed, which is more advantageous from the viewpoint of ease of handling of the biological adhesion film 10.

The promoter in the biological adhesion film 10 can be uniformly distributed in the thickness direction of the biological adhesion film 10. The promoter may be concentrated at a specific position in the biological adhesive film 10. For example, in the biological adhesion film 10, a plurality of regions in which the promoter is present at a high concentration may be present at predetermined intervals. The promoter may be present in a layer on the surface of the biological adhesive film 10. In this case, the layer of the accelerator may cover the entire base material made of regenerated cellulose or may cover a part of the base material.

In the biological adhesion film 10, the promoter may be present on the surface of the biological adhesion film 10 or may be present in the thickness direction of the biological adhesion film 10 other than the surface. For example, at least a part of the promoter in the biological adhesion film 10 is continuously present from the surface of the biological adhesion film 10 to the regenerated cellulose in the thickness direction of the biological adhesion film 10. In this case, as described above, the enhancer interacts with more, and thus the enhancer easily interacts with both the regenerated cellulose and the wearing agent, and the wearing of the biological adhesion film 10 to the biological tissue is more reliably promoted.

The regenerated cellulose is likely to form hydrogen bonds in or between molecules, and the biological adhesion membrane 10 is likely to have a dense structure. Therefore, the biological adhesion film 10 has high strength and appropriate flexibility, and is less likely to break, as described later. Further, since cellulose exhibits amphiphilicity, a hydrophilic active ingredient and a hydrophobic active ingredient can be appropriately supported, and the biological adhesion membrane 10 has high versatility.

The raw material of the regenerated cellulose is not particularly limited. For example, the raw material of the regenerated cellulose may be natural cellulose derived from plants, natural cellulose derived from organisms, regenerated cellulose such as cellophane, or processed cellulose such as cellulose nanofibers. The concentration of impurities in the regenerated cellulose raw material is advantageously 10% by weight or less.

The regenerated cellulose is, for example, cellulose substantially represented by the following formula (I). The term "cellulose substantially represented by the formula (I)" means cellulose in which at least 90% of hydroxyl groups of glucose residues in the cellulose represented by the formula (I) remain. The ratio of the number of hydroxyl groups of the glucose residue in the cellulose contained in the biological adhesion film 10 to the number of hydroxyl groups of the glucose residue in the cellulose represented by formula (I) can be quantified by a known method such as X-ray photoelectron spectroscopy (XPS). The regenerated cellulose contained in the biological patch film 10 may have a branched structure in some cases. The artificially derivatized cellulose typically does not correspond to "cellulose substantially represented by formula (I)". On the other hand, cellulose regenerated by derivatization is not excluded from "cellulose substantially represented by formula (I)". Even cellulose regenerated by derivatization may correspond to "cellulose substantially represented by formula (I)".

In the embodiment of the present disclosure, the biological adhesion film 10 is made of regenerated cellulose. The strength of a film formed from a suspension in which natural cellulose fibers are dispersed in water or the like is borne by hydrogen bonds between nanofibers constituting the cellulose fibers. Therefore, only brittle cellulose films can be obtained. In contrast, with a film made of regenerated cellulose, nanofibers unravel up to the unit of the molecular chain, and therefore the strength of the film made of regenerated cellulose is borne by hydrogen bonds between cellulose molecular chains. That is, for a film made of regenerated cellulose, hydrogen bonds of units smaller than nanofibers to each other are uniformly formed. Therefore, a cellulose film which has high strength, is suppressed in brittleness, has appropriate flexibility, and is less likely to break can be provided as compared with a case where a film is formed from a suspension in which fibers of natural cellulose are dispersed in water or the like. Here, the "nanofiber" is also referred to as "nanofibril (or microfibril)", which is the most basic unit of cellulose molecules assembled together, has a width of about 4nm to about 100nm, and has a length of, for example, about 1 μm or more.

In the present specification, "regenerated cellulose" refers to cellulose that does not have the crystal structure I peculiar to natural cellulose. The crystal structure of cellulose can be confirmed by XRD patterns. In the XRD pattern using CuK α rays, natural cellulose shows peaks near 14 to 17 ° and 23 ° peculiar to the crystal structure I, but regenerated cellulose tends to have a crystal structure II, peaks near 12 °, 20 ° and 22 °, and no peaks near 14 to 17 ° and 23 °.

For example, the regenerated cellulose that has not been chemically modified or derivatized is 90% or more of the regenerated cellulose contained in the biological patch film 10. It is desirable that the regenerated cellulose not chemically modified or derivatized is available in an amount of 98% by mass or more of the regenerated cellulose contained in the biological patch film 10. In this case, it is considered that cellulose which has not been chemically modified or derivatized is contained in a large amount in the biological patch film 10, and that cellulose contains more hydroxyl groups per 1 molecular chain. Therefore, it is considered that more hydrogen bonds are formed between the molecules of cellulose, and the biological adhesion membrane 10 tends to have high strength. The regenerated cellulose contained in the biological patch film 10 may be uncrosslinked.

The cellulose contained in the biological patch film 10 has, for example, 0 to 12% crystallinity. In this case, the amount of hydroxyl groups involved in the formation of the crystal structure is appropriately small, and the adhesion of the biological adhesive film 10 to the living body tends to be high. In addition, the biological adhesive film 10 can exhibit various functions by performing a predetermined chemical modification at a site where a hydroxyl group should be present.

The crystallinity of the cellulose included in the biological patch film 10 can be determined by, for example, Park et al, "cellulose crystallinity index: measurement technique and its influence on the interpretation of cellulase Performance (Cellulose crystallini)Use of the information reported by tyindex (measurement technologies and interference on prediction cellular analysis) Biotechnology for Biofuels 2010,310¹³C-NMR method. According to the method, the solid is passed through¹³A peak in the vicinity of 87 to 93ppm in a spectrum obtained by C-NMR measurement is considered to be derived from a crystal structure, a broad peak in the vicinity of 80 to 87ppm is considered to be derived from an amorphous structure, and when the former peak area is represented by X and the latter peak area is represented by Y, the crystallinity is determined by the following formula. In the following formula, "×" represents a multiplication operation.

(crystallinity)% (X/(X + Y)) × 100

As described above, the biological adhesion film 10 has a thickness of 20 to 5000 nm. If the thickness of the biological adhesion film 10 is 20nm or more, the biological adhesion film 10 has high strength and is easy to handle. Therefore, the biological adhesion film 10 can function as a self-supporting film that can be adhered to a biological tissue. If the thickness of the biological adhesion film 10 is 5000nm or less, the biological adhesion film 10 is less likely to peel off when the biological adhesion film 10 is worn on a biological tissue. In addition, if the thickness of the biological adhesion film 10 is within such a range, the biological adhesion film 10 can be easily peeled from the biological tissue by running water, for example. The thickness of the biological adhesion film 10 is determined by, for example, measuring the thicknesses of the biological adhesion film 10 at a plurality of positions and averaging the thicknesses. The thickness of each site can be measured, for example, using a Stylus profilometer system (Stylus profiling system) DEKTAK (registered trademark) manufactured by ブルカーナノインコーポレイテッド.

The thickness of the biological adhesion film 10 may be 100nm or more. If the thickness of the biological adhesion film 10 is 100nm or more, the strength of the biological adhesion film 10 is improved, and the biological adhesion film 10 can be handled easily. The thickness of the biological adhesion film 10 may be 300nm or more. When the thickness of the biological adhesion film 10 is 300nm or more, the strength of the biological adhesion film 10 is further improved, and the biological adhesion film 10 is not easily broken and can be easily used. The thickness of the biological adhesion film 10 may be 500nm or more. When the thickness of the biological adhesion film 10 is 500nm or more, more effective components such as cosmetic components can be retained in the biological adhesion film 10. The thickness of the biological adhesion film 10 may be 2000nm or less. If the thickness of the biological adhesion film 10 is 2000nm or less, the biological adhesion film 10 has high adhesion to a biological tissue, and the biological adhesion film 10 can be stably adhered to the surface of a biological tissue such as skin. The thickness of the biological adhesive film 10 may be 1300nm or less. When the thickness of the biological adhesion film 10 is 1300nm or less, the biological adhesion film 10 has higher adhesiveness to a biological tissue, and the state in which the biological adhesion film 10 is stably adhered to the surface of a biological tissue such as skin for a long period of time can be maintained.

The regenerated cellulose has, for example, a weight average molecular weight of 30,000 or more. In this case, the thickness of the biological adhesion film 10 can be 5000nm or less. The weight average molecular weight of the regenerated cellulose can be determined by, for example, Gel Permeation Chromatography (GPC).

The regenerated cellulose may have a weight average molecular weight of 150,000 or more. In this case, even if the thickness of the biological adhesion film 10 is adjusted to 1300nm or less, the biological adhesion film 10 can be made to be a self-supporting film.

The shape of the biological adhesion film 10 is not particularly limited when the biological adhesion film 10 is viewed in a plan view. The biological adhesion film 10 may have a circular shape, an elliptical shape, or a polygonal shape in a plan view. The biological adhesion film 10 may have an indefinite shape in a plan view.

The biological adhesion film 10 may be a single-layer film or a film having a laminated structure in which a plurality of layers are laminated. When the biological adhesion film 10 has a laminated structure, the active ingredients held by the plurality of layers may be the same or different for each layer. The biological patch film 10 may have a laminated structure in which a layer containing regenerated cellulose and a layer made of a material other than regenerated cellulose are laminated.

In the case of cosmetic use, the film 10 for biological application is used for, for example, (i) skin care such as whitening, moisturizing, and anti-wrinkle, (ii) hair care such as hair raising, hair increasing, depilation, and hair styling, or (iii) color cosmetics such as foundation, face powder, and nail. In the case of medical use, the film 10 for biological application can be used for administration to living bodies of medicines such as analgesic and anti-inflammatory drugs, cardiotonic drugs, antifungal drugs, adrenocortical hormone drugs, and blood circulation-promoting drugs.

The biological patch film 10 may contain components other than regenerated cellulose and an accelerator. For example, the biological adhesive film 10 may contain a predetermined active ingredient. The accelerator may also serve as an active ingredient. The active ingredient can be, for example, a whitening ingredient, an ultraviolet ray protection ingredient, a moisturizing ingredient, a hair growth ingredient, a cosmetic ingredient such as a cosmetic or a medicinal ingredient. Examples of the cosmetic ingredients include acacia, tragacanth, galactan, guar gum, carob gum, karaya gum, carrageenan, pectin, agar, quince seed (quince), brown algae colloid (アルゲコロイド, brown algae extract), starch (rice, corn, potato, wheat), succinoglycan, casein, albumin, gelatin, mucin, chondroitin sulfate, xylitol, maltose, sodium pyrrolidone, retinol, retinal, retinoic acid and other vitamin A, thiamine, riboflavin, pyridoxine, pyridoxamine, folic acid and other vitamin B, ascorbic acid (sodium) and other vitamin C, ergocalciferol, cholecalciferol and other vitamin D, alpha-tocopherol and other vitamin E, phylloquinone, menadione and other vitamin K, retinoic acid, palmitic acid and other vitamin A derivatives, furathiamine and other vitamin B derivatives, vitamin C, vitamin D derivatives, vitamin D, vitamin E, vitamin A derivatives, vitamin B derivatives, vitamin C, palmitic acid and vitamin C derivatives, vitamin, Vitamin C derivatives such as glycerol ascorbate and ascorbyl tetrahexyldecanoate, vitamin D derivatives such as tachysterol, vitamin E derivatives such as alpha-tocopherol acetate, alpha-tocopherolquinone, and alpha-tocopherol succinate, polyphenols such as hydroquinone, 4-methoxysalicylate, 4-n-butylresorcinol, and anthocyanin, disodium 3-succinylglycyrrhetinate, placenta, dihydroxy benzone, 2-ethylhexyl 4-methoxycinnamate, various amino acids, keratin, hydroxyapatite, tricalcium phosphate, calcium carbonate, ceramics such as aluminum oxide, zirconium oxide, chitin, chitosan, arbutin, ellagic acid, kojic acid, tranexamic acid, glycerol, sodium lactate, hyaluronic acid, ceramide, minoxidil, finasteride, collagen, elastin, various extracts, vitamin D derivatives such as alpha-tocopherol acetate, alpha-hydroxy quinone, and alpha-tocopheryl succinate, ceramics such as chitin, chitosan, arbutin, ellagic acid, kojic acid, tranexamic acid, hyaluronic acid, ceramide, minoxidil, fina, Citric acid, lecithin, carbomer, xanthan gum, dextran, palmitic acid, lauric acid, petrolatum, titanium oxide, iron oxide, synthetic pigments, dyes, phenoxyethanol, fullerene, astaxanthin, coenzyme, human oligopeptide, glycerol, diglycerin, sorbitol, pyrrolidone carboxylic acid, polyglycerol fatty acid ester, polyglycerol, jojoba oil, trimethylglycine, mannitol, trehalose, glycosyl trehalose, pullulan, erythritol, elastin, dipropylene glycol, butylene glycol, ethyl ethylhexanoate, sodium acrylate, disodium ethylenediaminetetraacetate, sucrose fatty acid ester, squalane, polyethylene glycol, polyoxyethylene hydrogenated castor oil, glyceryl stearate, ethanol, polyvinyl alcohol, hydroxyethyl cellulose, or ectoin. Examples of the pharmaceutically effective ingredient are cepharanthine, rutin, isosorbide dinitrate, indomethacin, diflucortolone valerate, acyclovir, ketoconazole, ketoprofen, diclofenac sodium, dexamethasone propionate, felbinac, clobetasol propionate, loxoprofen, methyl salicylate, or tacrolimus. These active ingredients can be contained in the biological patch film 10 in the form of a solid, a solution, a dispersion, or an emulsion.

At least a part of the biological adhesion film 10 may be colored. For example, at least a part of the biological patch film 10 may be colored to a color close to the skin color. In this case, the skin spots, moles, and scars can be covered with the biological patch film 10 so as to be inconspicuous.

The biological adhesive film 10 is used by being adhered to the skin or nails of a person, for example, the face, the arms, or the like. Therefore, the biological patch film 10 typically has a thickness of 7mm²The above area. This makes it possible to cover a wide area when the biological adhesive film 10 is adhered to the skin. The biological adhesion film 10 may be attached to the surface of a biological tissue other than the skin, such as an organ. By attaching the biological patch film 10 to the surface of the organ, the healing of the organ can be promoted. In addition, healing of organs can be prevented.

The wearing agent is not particularly limited as long as it contains water. The wearing agent is, for example, 1 selected from the group consisting of pure water, distilled water, physiological saline, cosmetic water containing water, emulsion containing water, cosmetic liquid containing water, and cream containing water. The ratio of the mass of water to the mass of the wearing agent is not particularly limited. For example, the ratio is 1% or more. In this case, the biological adhesion film 10 can be easily worn on the biological tissue. More preferably 10% or more. In this case, the biological adhesion film 10 can be more easily worn on the biological tissue. The wearing preparation contains, for example, water, fat, alcohol, or an emulsifier, and may further contain the above 1 or more active ingredients.

In one example of a cosmetic method of attaching the biological adhesion film 10, a wearing agent containing water is attached to a living tissue and the biological adhesion film 10, and the biological adhesion film 10 is attached to the living tissue. The order of the supply of the wearing agent and the operation of bringing the biological adhesion film 10 close to the living tissue is not particularly limited. For example, the wearing preparation may be dropped onto the biological adhesion film 10 and the biological tissue in a state where the biological adhesion film 10 is in contact with the biological tissue. After the preparation is dropped onto the living tissue, the biological adhesion film 10 may be brought into contact with the preparation adhering to the living tissue.

The wearing agent may contain a polyhydric alcohol. In this case, the biological adhesion film 10 can be more easily worn on the biological tissue. The polyol is not particularly limited. The polyhydric alcohol is, for example, at least 1 of glycerin and propylene glycol. In this case, the biological adhesion film 10 has high adhesion to the biological tissue, and the biological adhesion film 10 can be worn on the biological tissue in a short time. The ratio of the mass of propylene glycol to the mass of the wearing agent is, for example, 5 to 15 mass%. The ratio of the mass of glycerin to the mass of the wearing agent is, for example, 5 to 10%. When the wearing preparation contains propylene glycol or glycerin in such a ratio, the adhesiveness of the biological adhesion film 10 to the biological tissue is further improved, and the possibility that the biological adhesion film 10 can be worn on the biological tissue in a shorter time is improved.

As shown in fig. 1, the biological adhesion film 10 is provided in the form of a laminate 50a, for example. The laminate 50a includes the biological adhesion film 10 and the first protective layer 21. The biological adhesive film 10 has a first main surface 11 and a second main surface 12. The second main surface 12 is located on the opposite side of the first main surface 11 in the biological adhesion film 10. The first protective layer 21 is disposed on the first main surface 11. The first protective layer 21 is a layer that can be removed from the first main surface 11. The first protective layer 21 is, for example, in contact with the first main surface 11.

The first protective layer 21 may be, for example, (i) a sheet, woven fabric, nonwoven fabric, or mesh of a polymer material such as polyethylene, polypropylene, polyethylene terephthalate, nylon, acrylic resin, polycarbonate, polyvinyl chloride, acrylonitrile/butadiene/styrene (ABS) resin, polyurethane, synthetic rubber, cellulose, テフロン (registered trademark), aramid, or polyimide, (ii) a sheet-like metal, or (iii) a sheet-like glass. The whole or a part of the surface of the first protective layer 21 may be subjected to chemical or physical surface treatment. The first protective layer 21 has a shape which is the same as or different from the shape of the biological adhesive film 10 in a plan view, and has a size which is the same as or different from the size of the biological adhesive film 10. For example, a plurality of biological adhesion films 10 may be disposed on a single first protective layer 21. Further, the biological adhesion film 10 can maintain its shape without the first protective layer 21. Therefore, even if the first protective layer 21 is removed from the first main surface 11, the shape of the biological adhesion film 10 can be maintained.

As shown in fig. 2A, for example, the second main surface 12 of the biological adhesion film 10 is brought close to the laminate 50a toward a specific part of a living body (for example, skin), and the second main surface 12 of the biological adhesion film 10 is brought into contact with the specific part of the living body. At this time, the wearing agent is supplied to a specific part of the living body or the film 10 for biological adhesion. Next, as shown in fig. 2B, the first protective layer 21 is peeled off from the first main surface 11 of the biological adhesive film 10. At this time, the biological adhesion film 10 is in close contact with the living tissue, and the state in which the biological adhesion film 10 is adhered to the living tissue is maintained. If the first protective layer 21 is completely peeled off, the entire first main surface 11 of the biological adhesive film 10 is exposed as shown in fig. 2C.

The laminate 50a may be modified as shown in fig. 3 as laminate 50 b. The laminate 50b is configured in the same manner as the laminate 50a, except for the case where it is specifically described. The same reference numerals are given to the same or corresponding components of the laminate 50b as or to the laminate 50a, and detailed description thereof is omitted. The description about the laminate 50a is also applicable to the laminate 50b as long as there is no technical contradiction.

As shown in fig. 3, the laminate 50b further includes a second protective layer 22. The second protective layer 22 is disposed on the second main surface 12. The second main surface 12 may be protected by a second protective layer 22. In addition, the second protective layer 22 facilitates handling of the laminate 50 b.

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

The second protective layer 22 is typically removable from the second main surface 12. When the laminate 50b is used, for example, first, the second protective layer 22 is peeled off from the biological adhesion film 10. Thereby, the second main surface 12 is exposed. Then, the second main surface 12 is brought close to a specific part of a living body, and the living body sticking film 10 is stuck to the specific part of the living body in the same manner as the method of using the laminate 50 a.

Polylactic acid has been proposed as a material for a sheet to be attached to the skin. However, polylactic acid is a hydrophobic material and is not suitable for long-term use because of a fear of stuffiness and the like. Therefore, in applications such as application to the skin, irritation of the adhesive to the skin and water vapor permeability of the adhesive need to be considered.

On the other hand, when the thickness of the biological adhesive film 10 is 1300nm or less, the biological adhesive film can be attached to the skin 200 without using an adhesive. The reason why the film for biological adhesion 10 can be adhered to the skin without an adhesive even when the thickness is 500nm or more is presumably because the film exhibits softness even when the film has a thickness of 500nm or more and easily follows irregularities (for example, curved surfaces such as the face and arms), and therefore, the influence of the functional groups on the surface of the cellulose film and the van der waals force is larger than that of the polylactic acid film, and the adhesiveness is improved. Since the biological patch film 10 can be attached to the skin without an adhesive, it can be used for a long time with reduced stuffiness and the like. Further, cellulose is biocompatible, hardly exerts physical or chemical stress on the skin even when it is directly attached to the skin, and is amphiphilic, hydrophilic and insoluble in water, so that it is not likely to be dissolved by moisture such as sweat, and has excellent durability.

An example of the method for producing the biological adhesion film 10 will be described. First, a cellulose solution is prepared by dissolving cellulose in a solvent. To obtain a regenerated cellulose film having a weight average molecular weight of 30,000 or more, cellulose having a weight average molecular weight of at least 30,000 or more is used. Thus, a self-supporting biological adhesive film having a thickness of 5000nm or less can be produced. In order to obtain a regenerated cellulose film having a weight average molecular weight of 150,000 or more, a cellulose solution may be prepared using cellulose having a weight average molecular weight of at least 150,000 or more. In this case, a self-supporting biological adhesive film having a thickness of 1300nm or less can be produced. By making the weight average molecular weight of the cellulose used in the prepared cellulose solution large as described above, more hydroxyl groups are contained in 1 molecular chain, so that a large number of intermolecular hydrogen bonds can be formed, and a thinner biological adhesive film can be stably produced. The cellulose used for preparing 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, for example, cellulose derived from plants such as pulp and cotton, or cellulose biologically produced by bacteria. The impurity concentration in the raw material of cellulose is, for example, 10 wt% or less. If the weight average molecular weight of the regenerated cellulose is 2,000,000 or less, the handling becomes easy and therefore it is useful. It is further desirable that the regenerated cellulose has a weight average molecular weight of 1,000,000 or less.

The solvent is, for example, a solvent containing at least an ionic liquid (1 st solvent). By using the 1 st solvent, cellulose can be dissolved in a relatively short time. The ionic liquid is a salt composed of an anion and a cation, and can exhibit a liquid state at a temperature of 150 ℃ or lower. The ionic liquid contained in the 1 st solvent is, for example, an ionic liquid containing an amino acid or an alkyl phosphate. When the 1 st solvent contains such an ionic liquid, the cellulose can be dissolved while suppressing the decrease in molecular weight of the cellulose. In particular, since amino acids are components present in living bodies, an ionic liquid containing amino acids is advantageous for forming the biological adhesive film 10 that is safer for living bodies.

The cellulose can be dissolved using an ionic liquid that has been diluted in advance with a solvent that does not precipitate cellulose. For example, as the 1 st solvent, a mixture of an aprotic polar solvent and an ionic liquid may be used. The aprotic polar solvent is not easy to form hydrogen bonds and to precipitate cellulose.

The ionic liquid contained in the 1 st 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 the formula (II), in the ionic liquid, the anion includes a terminal carboxyl group and a terminal amino group. The cation of the ionic liquid of formula (II) may be a quaternary ammonium cation.

In the formula (II), R₁～R₆Independently represents a hydrogen atom or a substituent. The substituent may be an alkyl group, a hydroxyalkyl group, or a phenyl group. The substituents may comprise branches in the carbon chain. The substituent may include 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 1 st solvent may be an ionic liquid represented by the following formula (III). In the formula (III), R₁、R₂、R₃And R₄Independently represents a hydrogen atom or an alkyl group having 1 to 4 carbon atoms.

In the step of preparing the cellulose solution, a 2 nd solvent may be further added. For example, a 2 nd solvent may be further added to a mixture of cellulose having a prescribed weight average molecular weight and the 1 st solvent. The 2 nd solvent is, for example, a solvent which does not precipitate cellulose. The 2 nd solvent may be an aprotic polar solvent.

The concentration of cellulose in the cellulose solution is typically 0.2 to 15% by weight. If the cellulose concentration of the cellulose solution is 0.2 wt% or more, the biological adhesion film 10 having a strength necessary for keeping the shape thereof can be obtained while making the thickness of the biological adhesion film 10 thin. Further, if the concentration of cellulose in the cellulose solution is 15% by weight or less, precipitation of cellulose in the cellulose solution can be suppressed. The cellulose concentration of the cellulose solution may be 1 to 10% by weight. If the cellulose concentration of the cellulose solution is 1 wt% or more, the biological patch film 10 having higher strength can be obtained. If the cellulose concentration of the cellulose solution is 10% by weight or less, a stable cellulose solution in which the deposition of cellulose is further reduced can be prepared.

Next, a cellulose solution was 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 respect to water is, for example, 70 ° or less. In this case, the cellulose solution has appropriate wettability to the substrate, 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, the cellulose solution can be prevented from entering the substrate, and the biological attachment film 10 can be easily separated from the substrate in a subsequent step.

The substrate may be chemically or physically surface modified. As the substrate, for example, a substrate of a polymer material subjected to surface modification treatment such as Ultraviolet (UV) irradiation or corona treatment can be used. The method of surface modification is not particularly limited. For example, coating, surface modification, plasma treatment, sputtering, etching, or spraying of a surface modifier can be applied.

Examples of a method for forming a liquid film of a cellulose solution on a substrate include gap coating in which a predetermined gap is formed between the liquid film and the surface of the substrate by an applicator or the like, slot die coating (slot die coating), spin coating, coating using a bar coater (Metering rod coating), gravure coating, and the like. The thickness of the liquid film is adjusted by adjusting the thickness of the gap, the size of the opening of the slot die, the coating speed, the rotational speed of the spin coating, the depth of the groove of the bar coater or gravure coating, the coating speed, and the like, and the thickness of the liquid film and the concentration of the cellulose solution are adjusted to adjust the thickness of the biological adhesion film. The method for forming a liquid film of the cellulose solution on the substrate may be a casting method, screen printing using a doctor blade (squeegee), spray coating, or electrostatic spraying.

At least one of the cellulose solution and the substrate may be heated while the substrate forms a liquid film of the cellulose solution. The heating may be performed, for example, in a temperature range (e.g., 40 to 100 ℃) capable of stably maintaining the cellulose solution.

The liquid film of cellulose solution formed on the substrate may be heated. The liquid film may be heated at a temperature (for example, 50 to 200 ℃) lower than the decomposition temperature of the ionic liquid contained in the 1 st solvent. By heating the liquid film at such a temperature, a solvent (for example, the 2 nd solvent or the like) other than the ionic liquid can be appropriately removed, and the strength of the biological adhesion film 10 tends to be high. The heating of the liquid film may be performed under a reduced pressure environment. In this case, the solvent other than the ionic liquid can be removed moderately in a shorter time at a temperature lower than the boiling point of the solvent.

After the liquid film of the cellulose solution is formed on the substrate, the liquid film may be gelled. For example, a liquid film can be gelled by exposing the liquid film to a vapor of a liquid that can be dissolved in an ionic liquid and does not dissolve cellulose, thereby obtaining a polymer gel sheet. For example, if the liquid film is left in an environment with a relative humidity of 30 to 100% RH, the ionic liquid in the liquid film comes into contact with water, and the solubility of cellulose in the liquid film decreases. This causes a part of the cellulose molecules to precipitate, and a 3-dimensional structure is formed. As a result, the liquid film gelled. The presence or absence of the gelation point can be judged by whether or not the gelled film can be lifted.

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 or 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 polymer gel sheet. This step can be understood as a step of washing the polymer gel sheet. In this step, in addition to the ionic liquid, a part of components (for example, the 2 nd solvent) other than the cellulose and the ionic liquid, among the components contained in the cellulose solution, may be removed. The rinse solution is typically a liquid that is soluble in the ionic liquid. Examples of such liquids are water, methanol, ethanol, propanol, butanol, octanol, toluene, xylene, acetone, acetonitrile, dimethylacetamide, dimethylformamide, and dimethylsulfoxide.

Next, the polymer gel sheet is immersed in a solution of an accelerator. In this case, the accelerator solution may further contain the above-mentioned active ingredient. The solvent in the solution of the accelerator is, for example, at least 1 selected from the group consisting of water, ethanol, propanol, butanol, acetone, glycerol, propylene glycol, 1, 3-butylene glycol, 1, 4-butylene glycol, diglycerol, polyethylene glycol, and polydimethylsiloxane. Instead of dipping the polymer gel sheet in a solution of the accelerator, the accelerator may be attached to the polymer gel sheet by spraying, vapor deposition, or coating. The polymer gel sheet may be immersed in a solution, dispersion, or emulsion containing the above active ingredient, separately from the immersion in the solution of the accelerator.

Then, 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, drying methods such as natural drying, vacuum drying, heat drying, freeze drying, and supercritical drying can be applied. The drying method of the polymer gel sheet can be vacuum heating. The conditions for drying the polymer gel sheet are not particularly limited. The conditions for drying the polymer gel sheet are selected to be sufficient time and temperature for removing the No. 2 solvent and the rinse solution. The solvent is removed from the polymer gel sheet, thereby obtaining the biological adhesion film 10.

In the step of drying the polymer gel sheet, for example, in the case of freeze drying, a solvent which can be frozen and has a boiling point of about 100 to 200 ℃ is used. The freeze-drying can be carried out using a solvent such as water, t-butanol, acetic acid, 1,2,2,3,3, 4-heptafluorocyclopentane, or dimethyl sulfoxide.

In the above method, the polymer gel sheet may be immersed in a solution of the accelerator before the polymer gel sheet is dried, or the accelerator may be attached after the polymer gel sheet is dried. For example, a polymer sheet obtained by drying a polymer gel sheet may be immersed in a solution of an accelerator. In this case, the accelerator solution may further contain the above-mentioned active ingredient. Then, the impregnated polymer sheet is further dried. In this case, the accelerator may be attached to the polymer gel sheet by spraying, vapor deposition, or coating.