WO2019220700A1

WO2019220700A1 - Film for application to living body and cosmetic method in which film for application to living body is applied

Info

Publication number: WO2019220700A1
Application number: PCT/JP2019/004365
Authority: WO
Inventors: 知子川島; 谷池　優子; 佑紀波潟; 貴裕青木
Original assignee: パナソニックＩｐマネジメント株式会社
Priority date: 2018-05-17
Filing date: 2019-02-07
Publication date: 2019-11-21
Also published as: JPWO2019220700A1; JP7170232B2; CN111801090A; CN111801090B

Abstract

The present disclosure provides a film for application to the living body, which contains a regenerated cellulose and is advantageous for reducing the time required for attachment of regenerated cellulose to living tissues. A film (10) for application to the living body according to the present disclosure contains a regenerated cellulose and an accelerator. The accelerator accelerates attachment of the regenerated cellulose to living tissues. This film (10) for application to the living body is self-supporting, and has a thickness of from 20 nm to 5,000 nm. The accelerator has an HLB value of 4-18. This film (10) for application to the living body is able to maintain the shape without having a supporting body.

Description

Membrane for living body application and beauty method for attaching a film for living body attachment

The present disclosure relates to a living body adhesive film and a cosmetic method for attaching the biological adhesive film.

Conventionally, a membrane for biological application to be applied to biological tissue such as skin is known.

For example, Patent Document 1 describes a cosmetic method in which a coloring material such as a pigment is blended in a large amount, cosmetics such as a foundation do not adhere to clothes, etc., and has a so-called secondary adhesion-less effect. The thin film used in is also described. This thin film is composed of a base film and a support, and the base film has a thickness of 10 to 500 nm. In the cosmetic method described in Patent Document 1, a base film is attached to the skin, and the attached thin film support is removed. The material of the base film is a material such as polylactic acid. Components such as hyaluronic acid are supported on the base film.

International Publication No. 2014/058060

In the technique described in Patent Document 1, no study has been made on a membrane for bioadhesion containing regenerated cellulose. Therefore, the present disclosure provides a biomedical adhesive membrane that contains regenerated cellulose and is advantageous for shortening the time required for attachment to a biological tissue.

This disclosure
Regenerated cellulose, and an accelerator that promotes attachment of the regenerated cellulose to a living tissue,
A self-supporting type having a thickness of 20 to 5000 nm,
The accelerator has an HLB value of 4 to 18,
Provided is a membrane for bioadhesion.

Additional effects and advantages of the disclosed embodiments will become apparent from the specification and drawings. The effects and / or advantages are individually provided by the various embodiments or features disclosed in the specification and drawings, and not all are required to obtain one or more of these.

The above-mentioned membrane for bioadhesion is advantageous for shortening the time required for attachment to a living tissue while containing regenerated cellulose.

FIG. 1 is a cross-sectional view schematically illustrating an example of a laminated body of the present disclosure. FIG. 2A is a diagram illustrating a method of using the membrane for biological sticking of the present disclosure. FIG. 2B is a diagram illustrating a method of using the biomarker membrane of the present disclosure. FIG. 2C is a diagram illustrating a method of using the biomedical adhesive membrane of the present disclosure. FIG. 3 is a cross-sectional view schematically illustrating another example of the laminated body of the present disclosure.

(Knowledge that became the basis of this disclosure)
As described in Patent Document 1, polylactic acid is known as a material for a film attached to a living tissue such as skin. However, since polylactic acid exhibits hydrophobicity, problems such as stuffiness may occur, and it is considered that it is not always appropriate to apply a polylactic acid film to a living tissue for a long period of time. On the other hand, a cellulose film tends to have a high water vapor permeability and easily allows moisture such as sweat to pass through. For this reason, when a cellulose film is applied to the skin, discomfort caused by problems such as stuffiness can be reduced.

The present inventors have developed a self-supporting membrane for bioadhesive membrane having a thickness of several μm or less, made of regenerated cellulose, which has not been realized in the past. The inventors of the present invention have further studied the membrane for attaching to a living body, and have found that there is room for shortening the time required for attachment to a living tissue. Accordingly, the present inventors have repeated a great deal of trial and error in order to shorten the time required for mounting the bioadhesive membrane on the biological tissue. As a result, it has been newly found that the time required for attachment to a living tissue can be shortened by including a predetermined component in the bioadhesive membrane containing regenerated cellulose. Based on this new knowledge, the present inventors have devised a biomedical patch membrane according to the present disclosure.

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

(Item 1)
Regenerated cellulose, and an accelerator that promotes attachment of the regenerated cellulose to a living tissue,
A self-supporting type having a thickness of 20 to 5000 nm,
The accelerator has an HLB value of 4 to 18,
Membrane for living body application.

(Item 2)
Item 2. The bioadhesive membrane according to Item 1, wherein the regenerated cellulose has a weight average molecular weight of 30,000 or more.

(Item 3)
Item 3. The membrane for biological application according to Item 1 or 2, which has a thickness of 20 to 1300 nm.

(Item 4)
The membrane for bioadhesion 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)
Item 5. The biomedical adhesive film according to any one of Items 1 to 4, wherein the accelerator is a compound having an ethylene glycol chain or a polyethylene glycol chain.

(Item 6)
Item 1. The accelerator is at least one selected from the group consisting of a compound represented by the following formula (A), a compound represented by the following (B), and a compound represented by the following (C). 6. The membrane for biological application according to any one of 1 to 5.

In formulas (A), (B), and (C), each of a, b, c, d, and e is an integer of 0 or more, and at least one of a and b is an integer of 1 or more, c , D, and e are each an integer of 1 or more, f is an integer of 1 or more, and R ₁ and R ₂ are each independently an alkyl group, an alkoxy group, (poly) ethylene glycol (alkyl Ether) group or (poly) propylene glycol group.

(Item 7)
7. The biomedical adhesive membrane according to any one of items 1 to 6, wherein the content of the promoter in the bioadhesive membrane is 10 to 90% by weight.

(Item 8)
Examples of the accelerator include bisPEG-18 methyl ether dimethylsilane, polyoxyethylene (4) (6) sorbitan monooleate, polyoxyethylene (4) (6) sorbitan monolaurate, polyoxyethylene (4) (20 ) Sorbitan monolaurate, polyoxyethylene (4) (20) sorbitan monopalmitate, polyoxyethylene (4) (20) sorbitan monostearate, PEG-11 methyl ether dimethicone, PEG-9 dimethicone, PEG-9 methyl The membrane for bioadhesion according to any one of items 1 to 7, which is at least one selected from the group consisting of ether dimethicone and PEG / PPG-20 / 22 butyl ether dimethicone.

(Item 9)
A cosmetic method for affixing a membrane for bioadhesion,
The membrane for bioadhesion includes a regenerated cellulose and a promoter having an HLB value of 4 to 18 that promotes the attachment of the regenerated cellulose to a living tissue, and has a thickness of 20 to 5000 nm. And
Attaching a mounting agent containing an oily component to a living tissue and the membrane for attaching a living body, and attaching the membrane for attaching a living body to the living tissue,
Beauty method.

(Item 10)
Item 10. The cosmetic method according to Item 9, wherein the oil component is at least one selected from the group consisting of fatty acids, paraffin, naphthene, cycloparaffin, and silicone oil.

(Embodiment)
Hereinafter, embodiments of the present disclosure will be described with reference to the drawings. In addition, the following embodiment is only an illustration and the method for affixing the bioadhesive film and the bioadhesive film of the present disclosure is not limited to the following embodiment. Items such as numerical values, shapes, materials, components, arrangement of components, connection forms, steps, and order of steps shown in the following embodiments are examples, and are described for the purpose of limiting the present disclosure. Not a thing. The following various embodiments can be combined with each other as long as no contradiction arises. In addition, among the constituent elements in the following embodiments, constituent elements that are not described in the independent claims indicating the highest concept are not to be understood as essential constituent elements. In the following description, components having substantially the same function are denoted by common reference numerals, and description thereof may be omitted. In addition, in order to avoid the drawing from becoming excessively complicated, illustration of some elements may be omitted.

The membrane 10 for bioadhesive shown in FIG. 1 contains regenerated cellulose and an accelerator. The promoter promotes the attachment of the regenerated cellulose to the living tissue. The regenerated cellulose typically forms the skeleton (base material) of the bioadhesive membrane 10. The bio-adhesive membrane 10 is a self-supporting membrane having a thickness of 20 to 5000 nm. In the present specification, the “self-supporting membrane” means a membrane capable of maintaining the form of the membrane without a support. For example, when a self-supporting membrane is lifted by pinching a part of the self-supporting membrane with fingers or tweezers, the self-supporting membrane is not damaged without damaging the self-supporting membrane. It is possible to lift the whole. The accelerator has an HLB value of 4-18. In this specification, the HLB value means a value determined by the Griffin method. According to the Griffin method, it is defined as HLB value = 20 × (sum of formula weight of hydrophilic portion) / molecular weight.

Regenerated cellulose has abundant hydroxyl groups. In addition, the bioadhesive membrane 10 can be used with a mounting agent containing an oily component interposed between the bioadhesive membrane 10 and the biological tissue. When the accelerator has an HLB value of 4 or more, strong interaction such as hydrogen bonding may occur between the hydroxyxyl group of the regenerated cellulose and the accelerator. On the other hand, when the HLB value of the accelerator is 18 or less, the accelerator exhibits an appropriate hydrophobicity, and an appropriate amount of hydrophobic interaction or the like is present between the hydrophobic group of the fatty acid or silicone oil contained in the mounting agent and the accelerator. Interaction occurs. Therefore, when the accelerator has an HLB value of 4 to 18, an appropriate interaction occurs between the accelerator and the regenerated cellulose and the mounting agent. As a result, the promoter promotes the attachment of the regenerated cellulose to the living tissue, and can shorten the time required for the attachment to the living tissue. In addition, it is considered that this promoter does not easily interact with a membrane having high hydrophobicity such as a polylactic acid membrane, and it is difficult to promote attachment of the membrane having high hydrophobicity to a living tissue.

The accelerator is, for example, a compound having an ethylene glycol chain or a polyethylene glycol chain. In this case, the ethylene glycol chain or polyethylene glycol chain of the accelerator tends to interact with the hydroxyl group of the regenerated cellulose.

The accelerator includes a compound represented by the following formula (A), a compound represented by the following (B), and the following (
It may be at least one selected from the group consisting of compounds represented by C). In the formulas (A), (B), and (C), each of a, b, c, d, and e is an integer of 0 or more, at least one of a and b is an integer of 1 or more, and c , D, and e are each an integer of 1 or more, f is an integer of 1 or more, and R ₁ and R ₂ are each independently an alkyl group, an alkoxy group, (poly) ethylene glycol (alkyl Ether) group or (poly) propylene glycol group.

In Formula (A), if a and b are integers of 0 or more and at least one of a and b is an integer of 1 or more, the values of a and b are not particularly limited. Each of a and b is 18, for example. In this case, the accelerator has high safety.

In the formula (B), when c, d, and e are integers of 0 or more and at least one of c, d, and e is an integer of 1 or more, each of the values of c, d, and e Is not particularly limited. Each of c, d, and e can be, for example, 6-100. When each of c, d, and e is 6 or more, the hydrophilicity of the accelerator is high, and the accelerator easily flows. For this reason, it is easy to attach the bioadhesive membrane 10 to a biological tissue. When each of c, d, and e is 100 or less, the accelerator is likely to exist in a liquid state at room temperature (15 to 25 ° C.), and the bioadhesive membrane 10 can be easily attached to a living tissue. Each of c, d, and e may be 6-20. When each of c, d, and e is 20 or less, the HLB value of the accelerator can be easily adjusted to 4 to 18 by appropriately adjusting the chain length of R ₁ .

In the formula (B), the chain length is not particularly limited as long as R ₁ is an alkyl group, an alkoxy group, a (poly) ethylene glycol (alkyl ether) group, or a (poly) propylene glycol group. When R ₁ is an alkyl group or an alkoxy group, R ₁ has a molecular chain made of, for example, 8 to 30 carbon atoms. Such molecular chains are often present in the living body as substances such as sebum. For this reason, even if R ₁ is desorbed from the accelerator by hydrolysis, the fatty acid formed by the desorption of R ₁ is likely to have biocompatibility and hardly cause harm to the living body. In addition, when R ₁ is a (poly) ethylene glycol (alkyl ether) group or a (poly) propylene glycol group, R ₁ represents a molecular chain made of, for example, 1 to 1000 repeating units of ethylene glycol or propylene glycol. Have. Such molecular chains are safe because they are often used as, for example, cosmetic constituent substances. Therefore, even if R ₁ is desorbed from the accelerator by hydrolysis, the (poly) ethylene glycol (alkyl ether) group or (poly) propylene glycol group formed by the desorption of R ₁ is biocompatible. It is easy to have, and is hard to cause harm to the living body.

In the formula (C), f is not particularly limited as long as it is an integer of 1 or more. f may be 1 to 100, for example. When f is 1 or more, the accelerator is easily hydrophobic because the accelerator is somewhat hydrophobic. For this reason, it is easy to attach the bioadhesive membrane 10 to a biological tissue. When f is 100 or less, the accelerator is likely to exist in a liquid state at normal temperature (15 to 25 ° C.), and the bioadhesive membrane 10 can be easily attached to the living tissue.

In the formula (C), the chain length is not particularly limited as long as R ₂ is an alkyl group, an alkoxy group, a (poly) ethylene glycol (alkyl ether) group, or a (poly) propylene glycol group. When R ₂ is an alkyl group or an alkoxy group, R ₂ has a molecular chain made of, for example, 8 to 30 carbon atoms. Such molecular chains are often present in the living body as substances such as sebum. For this reason, even if R ₂ is desorbed from the accelerator by hydrolysis, the fatty acid formed by the desorption of R ₂ is likely to have biocompatibility and hardly cause harm to the living body. When R ₂ is a (poly) ethylene glycol (alkyl ether) group or a (poly) propylene glycol group, R ₂ has a molecular chain made of, for example, 1 to 1000 repeating units of ethylene glycol or propylene glycol. . Such molecular chains are safe because they are often used as, for example, cosmetic constituent substances. Therefore, even if R ₂ is desorbed from the accelerator by hydrolysis, (poly) ethylene glycol (alkyl ether) or (poly) propylene glycol formed by desorption of R ₂ has biocompatibility. Easy to do and less harmful to the body.

Examples of the accelerator include bisPEG-18 methyl ether dimethylsilane, polyoxyethylene (4) (6) sorbitan monooleate, polyoxyethylene (4) (6) sorbitan monolaurate, polyoxyethylene (4) ( 20) Sorbitan monolaurate, polyoxyethylene (4) (20) sorbitan monopalmitate, polyoxyethylene (4) (20) sorbitan monostearate, PEG-11 methyl ether dimethicone, PEG-9 dimethicone, PEG-9 It is at least one selected from the group consisting of methyl ether dimethicone and PEG / PPG-20 / 22 butyl ether dimethicone. In this case, the interaction between the accelerator, the regenerated cellulose, and the mounting agent is in a favorable state, and the biological patch membrane 10 is easily mounted on the living tissue in a short time.

The content of the promoter in the bioadhesive membrane 10 is, for example, 10 to 90% by weight. If the content of the promoter in the bioadhesive membrane 10 is 10% by weight or more, it is advantageous from the viewpoint of promoting the attachment of the bioadhesive membrane 10 to a living tissue. If the content of the promoter in the bioadhesive membrane 10 is 90% by weight or less, stickiness of the bioadhesive membrane 10 is suppressed, which is advantageous from the viewpoint of ease of handling of the bioadhesive membrane 10. The content of the promoter in the bioadhesive membrane 10 may be 15 to 50% by weight. If the content of the promoter in the bioadhesive membrane 10 is 15% by weight or more, it is more advantageous from the viewpoint of promoting the attachment of the bioadhesive membrane 10 to a living tissue. If the content of the promoter in the bioadhesive membrane 10 is 50% by weight or less, stickiness of the bioadhesive membrane 10 is further suppressed, which is more advantageous from the viewpoint of ease of handling of the bioadhesive membrane 10.

The promoter in the bioadhesive membrane 10 may be uniformly distributed in the thickness direction of the bioadhesive membrane 10. The promoter may be present concentrated on a specific location in the bioadhesive membrane 10. For example, in the bioadhesive membrane 10, a plurality of regions where the accelerator is present at a high concentration may exist at a predetermined interval. The promoter may be present in a layered manner on the surface of the biological patch membrane 10. In this case, the layer of the accelerator may cover the whole base material constituted by regenerated cellulose, or may cover a part of the base material. In the bioadhesive membrane 10, the promoter may be present on the surface of the bioadhesive membrane 10, or may exist other than the surface of the bioadhesive membrane 10 in the thickness direction. For example, at least a part of the promoter in the bioadhesive membrane 10 is continuously present between the surface of the bioadhesive membrane 10 and the regenerated cellulose in the thickness direction of the bioadhesive membrane 10. In this case, as described above, the accelerator is more likely to interact, more easily interact with both the regenerated cellulose and the mounting agent, and the mounting of the bioadhesive membrane 10 to the living tissue is more reliably promoted. .

In the regenerated cellulose, hydrogen bonds are likely to be formed within the molecule and / or between the molecules, and the bioadhesive membrane 10 tends to have a dense structure. For this reason, the membrane | film | coat 10 for biological sticking has high intensity | strength and has moderate softness | flexibility as mentioned later, and it is hard to tear. Since cellulose exhibits amphiphilic properties, it can appropriately carry a hydrophilic active ingredient and a hydrophobic active ingredient, and the membrane 10 for bioadhesion has high versatility.

The raw material of regenerated cellulose is not particularly limited. For example, the raw material of the regenerated cellulose can be plant-derived natural cellulose, bio-derived natural cellulose, regenerated cellulose such as cellophane, or processed cellulose such as cellulose nanofiber. It is advantageous that the concentration of impurities in the raw material of regenerated cellulose is 10% by weight or less.

Regenerated cellulose is, for example, cellulose substantially represented by the following formula (I). Here, “the cellulose substantially represented by the formula (I)” means a cellulose in which 90% or more of hydroxyl groups of glucose residues in the cellulose represented by the formula (I) remain. The ratio of the number of hydroxyl groups of glucose residues in cellulose contained in the biomedical membrane 10 to the number of hydroxyl groups of glucose residues in cellulose represented by formula (I) is, for example, X-ray photoelectron spectroscopy (XPS). ) And other known methods. In addition, the regenerated cellulose contained in the biological patch membrane 10 may include a branched structure depending on the case. The artificially derivatized cellulose typically does not fall under “substantially the cellulose represented by the formula (I)”. On the other hand, “cellulose substantially represented by the formula (I)” does not exclude cellulose regenerated through derivatization. Even cellulose regenerated through derivatization may fall under “substantially represented by formula (I)”.

In the embodiment of the present disclosure, the bioadhesive membrane 10 is made of regenerated cellulose. The strength of the membrane formed from a suspension of natural cellulose fibers dispersed in water or the like is borne by hydrogen bonds between the nanofibers constituting the cellulose fibers. Therefore, only a brittle cellulose film can be obtained. On the other hand, in the membrane composed of regenerated cellulose, the nanofibers are loosened up to the molecular chain unit, so the strength of the membrane composed of regenerated cellulose is borne by hydrogen bonds between cellulose molecular chains. . That is, in a film made of regenerated cellulose, hydrogen bonds between units smaller than those of nanofibers are uniformly formed. Therefore, compared with the case where a film is formed from a suspension in which natural cellulose fibers are dispersed in water or the like, it has high strength and suppresses brittleness and has appropriate flexibility, And the cellulose membrane which is hard to tear can be provided. Here, the “nanofiber” is also called “nanofibril (or microfibril)” and is the most basic unit in which cellulose molecules are assembled, and has a width of about 4 nm to about 100 nm, for example, about 1 μm. It has the above length.

In the present specification, “regenerated cellulose” means cellulose that does not have the crystal structure I unique to natural cellulose. The crystal structure of cellulose can be confirmed by an XRD pattern. The example of the XRD pattern (CuKα ray (50 kV, 300 mA)) of natural cellulose is shown. In the XRD pattern, peaks at around 14-17 ° and 23 °, which are peculiar to the crystal structure I, appear. Regenerated cellulose often has a crystalline structure II and has peaks around 12 °, 20 ° and 22 °, and no peaks around 14-17 ° and 23 °.

For example, 90% or more of the regenerated cellulose contained in the bioadhesive membrane 10 is 90% or more of regenerated cellulose that has not been chemically modified and derivatized. 98% or more of the regenerated cellulose contained in the bioadhesive membrane 10 may be 98% or more of regenerated cellulose that has not been chemically modified or derivatized. In this case, it is considered that the bioadhesive membrane 10 contains a large amount of cellulose that has not been chemically modified and derivatized, and contains more hydroxyl groups per molecular chain of cellulose. For this reason, it is thought that more hydrogen bonds are formed between the molecules of cellulose, and the bioadhesive membrane 10 tends to have high strength. The regenerated cellulose contained in the bio-adhesive membrane 10 may be uncrosslinked.

Cellulose contained in the membrane 10 for biological sticking has a crystallinity of 0 to 12%, for example. In this case, the amount of hydroxyl groups involved in the formation of the crystal structure is moderately small, and the bioadhesive film 10 tends to have high adhesion to the living body. In addition, the membrane | film | coat 10 for biological sticking can express various functions by making predetermined | prescribed chemical modification in the site where a hydroxyl group should exist.

The crystallinity of cellulose contained in the biological sticking film 10 is, for example, Park et al. "Cellulose crystallinity index: measurement techniques and their impact on interpreting cellulase performance" Biotechnology for Biofuels 2010, 3 10 have been reported in the ¹³ C -It can be determined by means of NMR. According to this method, in the spectrum obtained by solid-state ¹³ C-NMR measurement, a peak around 87 to 93 ppm is regarded as originating from the crystal structure, and a broad peak around 80 to 87 ppm is regarded as originating from the amorphous structure. When the 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, “x” represents multiplication.
(Crystallinity)% = (X / (X + Y)) × 100

As described above, the bioadhesive membrane 10 has a thickness of 20 to 5000 nm. If the thickness of the bioadhesive membrane 10 is 20 nm or more, the bioadhesive membrane 10 has high strength and is easy to handle. Therefore, the bioadhesive membrane 10 can function as a self-supporting membrane that can be affixed to a biological tissue. If the thickness of the bioadhesive membrane 10 is 5000 nm or less, the bioadhesive membrane 10 is difficult to peel off when the bioadhesive membrane 10 is attached to a biological tissue. Further, when the thickness of the bioadhesive membrane 10 is within such a range, for example, the bioadhesive membrane 10 can be easily peeled off from the living tissue by running water. The thickness of the bioadhesive membrane 10 is determined by, for example, measuring the thickness of the bioadhesive membrane 10 at a plurality of locations and averaging them. The thickness at each location can be measured using, for example, a stylus profiling system DEKTAK (registered trademark) manufactured by Bruker Nano Inc.

The thickness of the bioadhesive membrane 10 may be 100 nm or more. When the thickness of the bioadhesive film 10 is 100 nm or more, the strength of the bioadhesive film 10 is increased and the bioadhesive film 10 is easy to handle. The thickness of the bioadhesive membrane 10 may be 300 nm or more. When the thickness of the bioadhesive film 10 is 300 nm or more, the strength of the bioadhesive film 10 is further increased, and the bioadhesive film 10 is not easily broken and can be used easily. The thickness of the bioadhesive membrane 10 may be 500 nm or more. When the thickness of the bioadhesive film 10 is 500 nm or more, more active ingredients such as cosmetic ingredients can be held in the bioadhesive film 10. The thickness of the bioadhesive membrane 10 may be 2000 nm or less. When the thickness of the bioadhesive membrane 10 is 2000 nm or less, the adhesiveness of the bioadhesive membrane 10 to the biological tissue is high, and the bioadhesive membrane 10 can be stably adhered to the surface of the biological tissue such as skin. it can. The thickness of the bioadhesive membrane 10 may be 1300 nm or less. When the thickness of the bioadhesive membrane 10 is 1300 nm or less, the bioadhesive membrane 10 has higher adhesion to the biological tissue, and the bioadhesive membrane 10 is stably adhered to the surface of the biological tissue such as skin for a long time. Can be maintained.

Regenerated cellulose has a weight average molecular weight of, for example, 30,000 or more. In this case, a sheet having a thickness of 5000 nm or less can be produced. The weight average molecular weight of regenerated cellulose can be determined, for example, by 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 bioadhesive membrane 10 is adjusted to a thickness of 1300 nm or less, the bioadhesive membrane 10 can be produced as a self-supporting membrane.

The shape of the bioadhesive membrane 10 is not particularly limited when the bioadhesive membrane 10 is viewed in plan. The bioadhesive membrane 10 can be circular, elliptical, or polygonal in plan view. The bioadhesive membrane 10 may be indefinite in plan view.

The membrane 10 for bioadhesion may be a single-layer membrane or a membrane having a laminated structure in which a plurality of layers are laminated. When the biological sticking membrane 10 is a membrane having a laminated structure, the active ingredients retained in the plurality of layers may be the same or different for each layer. The bioadhesive membrane 10 may have a laminated structure in which a layer containing regenerated cellulose and a layer formed of a material other than regenerated cellulose are laminated.

In the case of cosmetic use, the bioadhesive membrane 10 is, for example, (i) skin care such as whitening, moisturizing, and wrinkle prevention, (ii) hair care such as hair growth, hair thickening, hair removal, and hair styling, or (iii) foundation, Used for makeup such as face powder and nail art. In the case of pharmaceutical use, the biomarker membrane 10 is used for administration of drugs such as analgesic / anti-inflammatory drugs, anti-inflammatory drugs, cardiotonic drugs, antifungal drugs, corticosteroid drugs, and blood circulation promoting drugs to the living body. Also good.

The membrane 10 for biological sticking may contain components other than regenerated cellulose and an accelerator. For example, the biomarking membrane 10 can contain a predetermined active ingredient. The active ingredient can be, for example, a cosmetic ingredient or a medicinal ingredient such as a whitening ingredient, an ultraviolet protection ingredient, a moisturizing ingredient, a hair-growth ingredient, and a cosmetic. The beauty ingredients are gum arabic, gum tragacanth, galactan, guar gum, carob gum, caraya gum, carrageenan, pectin, agar, quince seed (malmello), algae colloid (gypsum extract), starch (rice, corn, potato, wheat), saxino glucan, Vitamin A such as casein, albumin, gelatin, mucin, chondroitin sulfate, xylitol, maltose, sodium pyrrolidonecarboxylate, retinol, retinal, and retinoic acid, vitamin B such as thiamine, riboflavin, pyridoxine, pyridoxamine, and folic acid, ascorbic acid ( Vitamin C such as sodium), vitamin D such as ergocalciferol and cholecalciferol, vitamin E such as α-tocopherol, phylloquinone and Vitamin K such as naquinone, vitamin A derivatives such as tretinoin and retinol palmitate, vitamin B derivatives such as fursultiamine, vitamin C derivatives such as glyceryl ascorbic acid and ascorbyl tetrahexyldecanoate, vitamin D derivatives such as dihydrotaxosterol, acetic acid Vitamin E derivatives such as α-tocopherol, α-tocopherylquinone, and α-tocopherol succinate, hydroquinone, potassium 4-methoxysalicylate, lucinol, anthocyanins and other polyphenols, disodium 3-succinyloxyglycyrrhetinate, placenta, dioxybenzone 2-ethylhexyl 4-methoxycinnamate, various amino acids, keratin, hydroxyapatite, tricalcium phosphate, calcium carbonate, alumina, zirconi Ceramics, chitin, chitosan, arbutin, ellagic acid, kojic acid, tranexamic acid, glycerol, sodium lactate, hyaluronic acid, ceramide, minoxidil, finasteride, collagen, elastin, various extracts, citric acid, lecithin, carbomer, xanthan gum, dextran , Palmitic acid, lauric acid, petrolatum, titanium oxide, iron oxide, synthetic dye, dye, phenoxyethanol, fullerene, astaxanthin, coenzyme, human oligopeptide, glycerin, diglycerin, sorbitol, pyrrolidone carboxylic acid, fatty acid polyglyceryl, polyglycerin, jojoba Oil, trimethylglycine, mannitol, trehalose, glycosyl trehalose, pullulan, erythritol, elastin, dipropylene glyco , Butylene glycol, ethyl ethylhexanoate, sodium acrylate, edetate disodium, sucrose fatty acid ester, squalane, polyethylene glycol, polyoxyethylene hydrogenated castor oil, glyceryl stearate, ethanol, polyvinyl alcohol, hydroxyethyl cellulose, or Ectoin. Medicinal ingredients include, for example, cephalanthin, rutin, isosorbide nitrate, indomethacin, diflucortron valerate, acyclovir, ketoconazole, ketoprofen, diclofenac sodium, dexamethasone propionate, ferbinac, clobetasolpropionate, loxoprofen, methyl salicylate, or tacrolimus It is. These active ingredients can be contained in the bioadhesive membrane 10 in a solid, solution, dispersion, or emulsion state.

At least a part of the bioadhesive membrane 10 may be colored. For example, at least a part of the bioadhesive membrane 10 may be colored in a color close to the color of the skin. In this case, spots, moles, and scars on the skin can be covered with the bio-applied membrane 10 to make them inconspicuous.

The bioadhesive membrane 10 is used by being affixed to the skin or nails at sites such as the face and arms, for example. For this reason, the membrane 10 for biological sticking typically has an area of 7 mm ² or more. Thereby, a wide area | region can be covered when the membrane | film | coat 10 for biological sticking is affixed on skin. The bioadhesive membrane 10 may be affixed to the surface of a biological tissue other than skin such as an organ. By affixing the bioadhesive membrane 10 to the surface of the organ, healing of the organ can be promoted. In addition, adhesion between organs can be prevented.

The mounting agent is not particularly limited as long as it contains an oily component. In the present specification, the oily component refers to a substance that can dissolve only in water by 0.1% by mass or less. The oil component is, for example, at least one selected from the group consisting of fatty acids, paraffins, naphthenes, cycloparaffins, and silicone oils. The wearing agent is, for example, at least one selected from the group consisting of a lotion, a milky lotion, a cosmetic liquid, a cream, and an oil containing an oily component. The ratio of the mass of the oil component to the mass of the mounting agent is not particularly limited. This ratio is, for example, 1% or more. In this case, it is easy to wear the bioadhesive membrane 10. This ratio is desirably 10% or more. In this case, it is easier to wear the bioadhesive membrane 10. The kind of oil component is not particularly limited. As described above, the oil component is at least one selected from the group consisting of fatty acid, paraffin, naphthene, cycloparaffin, and silicone oil, for example. The fatty acid may be a (polyvalent) unsaturated fatty acid, a saturated fatty acid, a branched fatty acid, a cyclic fatty acid, or a fatty acid ester. It may be an ether type lipid. Fatty acids include, for example, caprylic acid, pelargonic acid, capric acid, lauric acid, myristic acid, pentadecylic acid, palmitic acid, palmitoleic acid, margaric acid, stearic acid, oleic acid, vaccenic acid, linoleic acid, linolenic acid, eleostearic acid Acid, arachidic acid, mead acid, arachidonic acid, behenic acid, lignoceric acid, nervonic acid, serotic acid, montanic acid, melicic acid, cyclobutanecarboxylic acid, cyclopentanecarboxylic acid, cyclohexanecarboxylic acid, cycloheptanecarboxylic acid, cyclooctane Glycerin fatty acid ester such as carboxylic acid, cyclononanecarboxylic acid, cyclodecanecarboxylic acid, cycloundecanecarboxylic acid, cyclobutenecarboxylic acid, cyclopentenecarboxylic acid, cyclohexenecarboxylic acid, cycloheptenecar Acid, cyclooctene carboxylic acid, cyclononene carboxylic acid, cyclodecene carboxylic acid, palm fatty acid methyl, lauric acid methyl, isopropyl myristate, palmitic sun isopropyl, methyl stearate, butyl stearate, isotridecyl stearate, methyl oleate, Myristyl myristate, stearyl stearate, isobutyl oleate, dinormal alkyl phthalate, diisononyl phthalate, didecyl phthalate, dialkyl phthalate, trinormal alkyl trimellitic acid, adipic acid ester, sorbitan monolaurate, sorbitan monopalmitate , Sorbitan monostearate, sorbitan monooleate, polyethylene glycol monolaurate, polyethylene glycol monostearate, polyethylene Glycol distearate, ethylene glycol distearate, propylene glycol monostearate, pentaerythritol monooleate, pentaerythritol monostearate, pentaerythritol tetrapalmitate, stearic acid monoglyceride, oleic acid monoglyceride, stearic acid mono-diglyceride, Or caprylic acid triglyceride. The mounting agent may contain a natural product-derived oil containing a fatty acid. Oils derived from natural products include, for example, argan oil, sukurwan oil, jojoba oil, horse oil, olive oil, camellia oil, rosehip oil, yuzu seed oil, macadamia nut oil, rice bran oil, almond oil, marla oil, apricot kernel Oil, arnica oil, walnut oil, olive skrawan oil, kyolot oil, kukui nut oil, grape seed oil, coconut oil, sunflower oil, sweet almond oil, sesame oil, tamanu oil, passion flower oil, peach kernel oil, hazelnut Oil, hemp seed oil, avocado oil, aloe vera oil, evening primrose oil, wheat germ oil, castor oil, camellia oil , Calendula oil, St. John's Wort oil, Hippofae oil, black seed oil, Borajioiru, mineral oil, or vegetable oils such as rose hip oil, an animal fat, or mine oil, and the like. The silicone oil is, for example, methylpolysiloxane, octamethyltrisiloxane, decamethylcyclopentasiloxane, octamethylcyclotetrasiloxane, methylpolysiloxane, dimethicone, dimethiconol, cyclomethicone, or amodimethicone. In addition, the wearing agent contains, for example, water, fats and oils, alcohol, or an emulsifier, and may further contain one or more active ingredients as described above.

In an example of a cosmetic method for attaching the bioadhesive membrane 10, an attachment agent containing an oil component such as fatty acid, paraffin, naphthene, cycloparaffin, or silicone oil is attached to the biological tissue and the bioadhesive membrane 10, thereby The bioadhesive membrane 10 is affixed to. The order of the supply of the mounting agent and the operation of bringing the biological sticking membrane 10 closer to the living tissue is not particularly limited. For example, the wearing agent may be dropped toward the bioadhesive membrane 10 and the biological tissue in a state where the bioadhesive membrane 10 is in contact with the biological tissue. Alternatively, after the mounting agent is dropped toward the living tissue, the living body adhesive film 10 may be brought into contact with the mounting agent attached to the living tissue.

As shown in FIG. 1, the bioadhesive membrane 10 is provided in the state of, for example, a laminate 50a. The laminated body 50 a includes the biological sticking film 10 and the first protective layer 21. The bioadhesive membrane 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 bioadhesive film 10. The first protective layer 21 is disposed on the first main surface 11. The first protective layer 21 is a layer removable from the first main surface 11. The first protective layer 21 is in contact with, for example, the first main surface 11.

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) (Trademark), aramid, and a sheet of polymer material such as polyimide, woven fabric, nonwoven fabric, or mesh, (ii) sheet-like metal, or (iii) 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 that is the same as or different from the shape of the bioadhesive membrane 10 in plan view, and has the same or different size as the bioadhesive membrane 10. For example, a plurality of bioadhesive membranes 10 may be disposed on the single first protective layer 21. The biological sticking membrane 10 can maintain its shape without the first protective layer 21. For this reason, even if the 1st protective layer 21 is removed from the 1st main surface 11, the film | membrane 10 for biological sticking can maintain the shape.

As shown in FIG. 2A, for example, the laminate 50a is brought close to the second main surface 12 of the bioadhesive membrane 10 toward a specific part (for example, skin) of the living body, and the second main surface 12 of the bioadhesive membrane 10 is placed. Is brought into contact with a specific part of the living body. At this time, the mounting agent is supplied to a specific part of the living body or the bioadhesive membrane 10. Next, as shown to FIG. 2B, the 1st protective layer 21 is peeled from the 1st main surface 11 of the film | membrane 10 for biological sticking. At this time, the bioadhesive membrane 10 is in close contact with the biological tissue, and the state where the bioadhesive membrane 10 is adhered to the biological tissue is maintained. When the first protective layer 21 is completely peeled off, the entire first main surface 11 of the bioadhesive membrane 10 is exposed as shown in FIG. 2C.

The laminated body 50a may be changed like a laminated body 50b shown in FIG. The laminated body 50b is configured in the same manner as the laminated body 50a unless otherwise described. Constituent elements of the laminated body 50b that are the same as or correspond to the constituent elements of the laminated body 50a are assigned the same reference numerals, and detailed descriptions thereof are omitted. The description regarding the stacked body 50a also applies to the stacked body 50b unless there is a technical contradiction.

As shown in FIG. 3, the stacked body 50 b further includes a second protective layer 22. The second protective layer 22 is disposed on the second major surface 12. The second main surface 12 can be protected by the second protective layer 22. Further, the second protective layer 22 facilitates handling of the stacked body 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 a shape that is the same as or different from the shape of the bioadhesive membrane 10 in plan view, and has the same or different size as the bioadhesive membrane 10. The second protective layer 22 has the same or different shape as the first protective layer 21 in 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 second main surface 12. When using the laminated body 50b, for example, first, the second protective layer 22 is peeled from the biomedical adhesive film 10. Thereby, the 2nd main surface 12 is exposed. Thereafter, the second main surface 12 is brought close to a specific part of the living body, and the bioadhesive film 10 is attached to the specific part of the living body in the same manner as in the method of using the laminate 50a.

Conventionally, 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 unsuitable for long-term use because of concerns about stuffiness. Therefore, it is necessary to consider the irritation that the adhesive gives to the skin and the water vapor permeability of the adhesive in applications such as application to the skin.

On the other hand, for example, when the thickness of the bioadhesive film 10 is 1300 nm or less, it can be applied to the skin without requiring an adhesive. The reason why it can be applied to the skin without an adhesive even if the thickness is 500 nm or more is that the biological adhesive film 10 shows flexibility even when it has a thickness of 500 nm or more, and has unevenness (for example, cheeks, arms, etc.) This is presumably because the influence of the functional group and van der Waals force on the surface of the cellulose film is increased and the adhesion is improved as compared with the polylactic acid film. Since it can be affixed to the skin without an adhesive, it is possible to use the bioadhesive membrane 10 for a long period of time while reducing stuffiness. Furthermore, cellulose has biocompatibility, is less susceptible to physical or chemical stress on the skin, even when applied directly to the skin, and is amphiphilic and hydrophilic. Since it has the property that it does not dissolve in water while it is held, it does not have to worry about being dissolved by moisture such as sweat, and has excellent durability.

An example of a method for manufacturing the biomedical adhesive membrane 10 will be described. First, cellulose is dissolved in a solvent to prepare a cellulose solution. In order 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. Thereby, the self-supporting type | mold membrane for biological sticking which has thickness of 5000 nm or less is producible. In order to obtain a regenerated cellulose membrane 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 biomedical adhesive film having a thickness of 1300 nm or less can be produced. Thus, by increasing the weight average molecular weight of cellulose used in the preparation of the cellulose solution, more hydroxyl groups are contained in one molecular chain. Thereby, it becomes possible to form many intermolecular hydrogen bonds, and a thinner membrane for biological application 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 produced by organisms such as bacteria. The impurity concentration in the cellulose raw material is, for example, 10% by weight or less. If the weight average molecular weight of the regenerated cellulose is 2,000,000 or less, it is useful because it is easy to handle. More desirably, the regenerated cellulose has a weight average molecular weight of 1,000,000 or less.

The solvent is, for example, a solvent (first solvent) containing at least an ionic liquid. By using the first solvent, cellulose can be dissolved in a relatively short time. An ionic liquid is a salt composed of an anion and a cation, and can exhibit a liquid state at a temperature of 150 ° C. or lower. The ionic liquid contained in the first solvent is, for example, an ionic liquid containing an amino acid or an alkyl phosphate ester. When the first solvent contains such an ionic liquid, cellulose can be dissolved while suppressing a decrease in the molecular weight of cellulose. In particular, since an amino acid is a component present in a living body, an ionic liquid containing the amino acid is advantageous for forming a safer biofilm 10 for a living body.

The cellulose may be dissolved by using an ionic liquid diluted in advance with a solvent that does not precipitate the cellulose. For example, a mixture of an aprotic polar solvent and an ionic liquid may be used as the first solvent. The aprotic polar solvent hardly forms hydrogen bonds and does not easily 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) may be a quaternary ammonium cation.

In the 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 a hydrogen atom or an alkyl group having 1 to 4 carbon atoms.

In the step of preparing the cellulose solution, a second solvent may be further added. For example, the second solvent may be further added to a 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 to 15% by weight. When the concentration of cellulose in the cellulose solution is 0.2% by weight or more, the bioadhesive membrane 10 having a strength necessary for maintaining the shape of the bioadhesive membrane 10 while reducing the thickness of the bioadhesive membrane 10 can be obtained. Moreover, if the density | concentration of the cellulose of a cellulose solution is 15 weight% or less, precipitation of the cellulose in a cellulose solution can be suppressed. The cellulose concentration of the cellulose solution may be 1 to 10% by weight. When the concentration of cellulose in the cellulose solution is 1% by weight or more, the bioadhesive membrane 10 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 precipitation of cellulose is further reduced can be prepared.

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 with respect to the water of the surface of a board | substrate is 70 degrees or less, for example. In this case, the wettability of the cellulose solution to the substrate is appropriate, and a liquid film that spreads 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 bioadhesive membrane 10 from the substrate in a subsequent process.

The substrate may be subjected to chemical or physical surface modification. As the substrate, for example, a polymer material substrate that has been subjected to surface modification treatment such as ultraviolet (UV) irradiation or corona treatment may be used. The method for surface modification is not particularly limited. For example, application of a surface modifier, surface modification, plasma treatment, sputtering, etching, or blasting can be applied.

A method for forming a liquid film of a cellulose solution on a substrate includes, for example, gap coating, slot die coating, spin coating, coating using a bar coater (Metering) that forms a predetermined gap with the surface of the substrate by an applicator or the like. rod coating) and gravure coating. Liquid film thickness adjusted by gap thickness or slot die opening size and coating speed, spin coat rotation speed, bar coater or gravure coat groove depth and coating speed, and cellulose solution concentration By adjusting the thickness, it is possible to adjust the thickness of the biomedical film. The method for forming the 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. This heating may be performed, for example, in a temperature range (for example, 40 to 100 ° C.) in which the cellulose solution can be kept stable.

The liquid film of the cellulose solution formed on the substrate may be heated. The liquid film may be heated, for example, at a temperature lower than the decomposition temperature of the ionic liquid contained in the first solvent (eg, 50 to 200 ° C.). By performing the heating of the liquid film at such a temperature, a solvent other than the ionic liquid (for example, the second solvent) can be appropriately removed, and the strength of the biological adhesive film 10 is likely to increase. The heating of the liquid film may be performed under a reduced pressure environment. In this case, a 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 the liquid film of the cellulose solution is formed on the substrate, the liquid film may be gelled. For example, by exposing the liquid film to vapor of a liquid that is soluble in an ionic liquid and does not dissolve cellulose, the liquid film can be gelled to obtain a polymer gel sheet. For example, when a 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, so that the solubility of cellulose in the liquid film decreases. Thereby, a part of cellulose molecule precipitates and a three-dimensional structure is formed. As a result, the liquid film is gelled. The presence or absence of a gel point can be determined by whether or not the gelled film can be lifted.

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

Next, the substrate and the polymer gel sheet are immersed in a rinsing 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 the components (for example, the second solvent) other than the cellulose and the ionic liquid may be removed from the components contained in the cellulose solution. The rinse liquid is typically a liquid that can be dissolved in an ionic liquid. 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 is immersed in the accelerator solution. At this time, the solution of the accelerator may further contain the above active ingredient. The solvent in the accelerator solution is, for example, a group consisting of water, ethanol, propanol, butanol, acetone, glycerin, propanediol, 1,3-butanediol, 1,4-butanediol, diglycerin, polyethylene glycol, and dimethicone. Is at least one selected from. Instead of immersing the polymer gel sheet in the accelerator solution, 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, a dispersion, or an emulsion containing the above active ingredient separately from the immersion of the accelerator in the solution.

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, drying methods such as natural drying, vacuum drying, heat drying, freeze drying, and supercritical drying can be applied. The polymer gel sheet may be dried by vacuum heating. The conditions for drying the polymer gel sheet are not particularly limited. As a condition for drying the polymer gel sheet, a time and temperature sufficient for removing the second solvent and the rinsing liquid are selected. By removing the solvent from the polymer gel sheet, the bioadhesive membrane 10 is obtained.

In the step of drying the polymer gel sheet, for example, when lyophilization is applied, a solvent that can be frozen and has a boiling point of about 100 to 200 ° C. is used. For example, lyophilization can be performed 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 the accelerator solution prior to drying the polymer gel sheet. However, the accelerator may be attached after the polymer gel sheet is dried. Good. For example, a polymer sheet obtained by drying a polymer gel sheet may be immersed in a promoter solution. At this time, the solution of the accelerator may further contain the above active ingredient. Thereafter, the polymer sheet after immersion is further dried. In this case, the accelerator may be attached to the polymer gel sheet by spraying, vapor deposition, or coating.

The membrane for bioadhesion of the present disclosure will be described in more detail by way of examples. In addition, the film | membrane for biological sticking of this indication is not limited to a following example. First, the evaluation test of the biomarker film according to each example and each comparative example will be described.

<Mounting test>
Various wearing agents were dropped on the skin inside the forearm. Tables 1 and 2 show the outline of the used mounting agent. Immediately after the mounting agent was dropped, the bioadhesive membrane of the laminate according to each example and each comparative example was brought into contact with the dropped mounting agent, and timing was started. Every time a predetermined time has elapsed since the start of timing, it was checked whether the bioadhesive membrane was attached to the skin, and the time required for the bioadhesive membrane to be attached to the skin (wearing time) was measured. . In addition, in the state where the bioadhesive membrane was attached to the skin, the nonwoven fabric of the laminate could be peeled off while the bioadhesive membrane adhered to the skin.

Example 1A
Cellulose derived from bleached pulp made from wood and having a purity of 90% or more was dissolved in an ionic liquid to prepare a cellulose solution. As the ionic liquid, an ionic liquid in which R ₁ is a methyl group, R ₂ , R ₃ , and R ₄ are ethyl groups in the formula (III) was used. A cellulose solution was applied onto the substrate to form a coating film. The thickness of the coating film was adjusted so that the thickness of the bioadhesive film was 400 nm. Thereafter, the coating film of the cellulose solution was gelled to form a polymer gel sheet. Thereafter, the substrate and the polymer gel sheet were washed with a predetermined rinse solution. Next, the washed polymer gel sheet was immersed in an aqueous solution of polyoxyethylene (4) (6) sorbitan monooleate (HLB value: 10.0), and then the polymer gel sheet was dried, according to Example 1A. A membrane for biopaste was obtained. The membrane for bioadhesion was removed from the substrate and laminated on the nonwoven fabric to obtain a laminate according to Example 1A. The membrane for bioadhesion was approximately 5 cm square in a plan view and had a transparent appearance. In addition, the structure of the biomedical adhesive membrane according to Example 1A was analyzed by X-ray diffraction (XRD). As a result, it was confirmed that the membrane for bioadhesion did not contain natural cellulose and was regenerated cellulose. The weight average molecular weight of the regenerated cellulose of the membrane for biopaste was determined by GPC measurement. The weight average molecular weight of the regenerated cellulose was 224,000.

Here, the concentration of polyoxyethylene (4) (6) sorbitan monooleate contained in the biomedical membrane was determined by the method described below. A plurality of polyoxyethylene (4) (6) sorbitans having different polyoxyethylene (4) (6) sorbitan monooleate concentrations previously dissolved in water with polyoxyethylene (4) (6) sorbitan monooleate An aqueous monooleate solution was prepared. Thereafter, the refractive index of each polyoxyethylene (4) (6) sorbitan monooleate aqueous solution was measured with a refractometer (manufactured by Atago Co., Ltd., product name: RX-5000α-Plus). A calibration curve was created from the concentration and refractive index of the polyoxyethylene (4) (6) sorbitan monooleate aqueous solution, and the slope a of the calibration curve was determined. The polyoxyethylene (4) (6) sorbitan monooleate contained in the biomedical membrane is extracted by immersing the biomedical membrane according to Example 1A in water for 1 hour and performing ultrasonic treatment. An extract of oxyethylene (4) (6) sorbitan monooleate was obtained. The refractive index n of this extract was measured with the above refractometer. Based on the refractive index n and the slope a of the calibration curve, the mass of polyoxyethylene (4) (6) sorbitan monooleate contained in the extract was determined. The mass of polyoxyethylene (4) (6) sorbitan monooleate contained in the extract was regarded as the mass of polyoxyethylene (4) (6) sorbitan monooleate contained in the biomedical patch membrane. The ratio of the mass of polyoxyethylene (4) (6) sorbitan monooleate contained in the biomedical membrane to the mass of the biomedical membrane was 20%.

(Example 1B)
Except for the following points, a biomedical adhesive membrane according to Example 1B and a laminate according to Example 1B were produced in the same manner as Example 1A. Instead of the polyoxyethylene (4) (6) sorbitan monooleate aqueous solution, a polyoxyethylene (4) (6) sorbitan monolaurate (HLB value: 13.3) aqueous solution was used. The dipping conditions were adjusted so that the ratio of the mass of the polyoxyethylene (4) (6) sorbitan monolaurate contained in the biomedical membrane to the mass of the biomedical membrane was 20%. The mass of the polyoxyethylene (4) (6) sorbitan monolaurate contained in the membrane for biological patch was determined according to the method described in Example 1A.

(Example 1C)
Except for the following points, a biomedical adhesive membrane according to Example 1C and a laminate according to Example 1C were produced in the same manner as Example 1A. Instead of the polyoxyethylene (4) (6) sorbitan monooleate aqueous solution, a polyoxyethylene (4) (20) sorbitan monolaurate (HLB value: 16.7) aqueous solution was used. The immersion conditions were adjusted such that the ratio of the mass of polyoxyethylene (4) (20) sorbitan monolaurate contained in the biomedical membrane to the mass of the biomedical membrane was 20%. The mass of the polyoxyethylene (4) (20) sorbitan monolaurate contained in the biomedical film was determined according to the method described in Example 1A.

(Example 1D)
Except for the following points, a biomedical adhesive membrane according to Example 1D and a laminate according to Example 1D were produced in the same manner as Example 1A. Instead of the polyoxyethylene (4) (6) sorbitan monooleate aqueous solution, a polyoxyethylene (4) (20) sorbitan monopalmitate (HLB value: 15.6) aqueous solution was used. The dipping conditions were adjusted so that the ratio of the mass of the polyoxyethylene (4) (20) sorbitan monopalmitate contained in the bioadhesive membrane to the mass of the bioadhesive membrane was 20%. The mass of the polyoxyethylene (4) (20) sorbitan monopalmitate contained in the biomedical film was determined according to the method described in Example 1A.

(Example 1E)
Except for the following points, a biomedical adhesive membrane according to Example 1E and a laminate according to Example 1E were produced in the same manner as Example 1A. Instead of the polyoxyethylene (4) (6) sorbitan monooleate aqueous solution, a polyoxyethylene (4) (20) sorbitan monostearate (HLB value: 14.9) aqueous solution was used. The dipping conditions were adjusted so that the ratio of the mass of the polyoxyethylene (4) (20) sorbitan monostearate contained in the bioadhesive membrane to the mass of the bioadhesive membrane was 20%. The mass of the polyoxyethylene (4) (20) sorbitan monostearate contained in the biomedical membrane was determined according to the method described in Example 1A.

(Example 1F)
Except for the following points, a biomedical adhesive membrane according to Example 1F and a laminate according to Example 1F were produced in the same manner as Example 1A. Instead of the polyoxyethylene (4) (6) sorbitan monooleate aqueous solution, a bisPEG-18 methyl ether dimethylsilane (HLB value: 17.8) aqueous solution was used. The immersion conditions were adjusted so that the ratio of the mass of bisPEG-18 methyl ether dimethylsilane contained in the bioadhesive membrane to the mass of the bioadhesive membrane was 20%. The mass of bisPEG-18 methyl ether dimethyl silane contained in the biopaste membrane was determined according to the method described in Example 1A.

(Example 1G)
Except for the points described below, a biomedical adhesive membrane according to Example 1G and a laminate according to Example 1G were produced in the same manner as Example 1A. Instead of the polyoxyethylene (4) (6) sorbitan monooleate aqueous solution, a PEG-11 methyl ether dimethicone (HLB value: 14.5) aqueous solution was used. The dipping conditions were adjusted so that the ratio of the mass of PEG-11 methyl ether dimethicone contained in the bioadhesive membrane to the mass of the bioadhesive membrane was 20%. The mass of PEG-11 methyl ether dimethicone contained in the membrane for biopsy was determined according to the method described in Example 1A.

Example 1H
Except for the following points, a biological adhesive film according to Example 1H and a laminate according to Example 1H were produced in the same manner as Example 1A. Instead of the polyoxyethylene (4) (6) sorbitan monooleate aqueous solution, an aqueous solution of PEG-9 dimethicone (HLB value: 10.0) was used. The immersion conditions were adjusted so that the ratio of the mass of PEG-9 dimethicone contained in the bioadhesive membrane to the mass of the bioadhesive membrane was 20%. The mass of PEG-9 dimethicone contained in the membrane for biopsy was determined according to the method described in Example 1A.

Example 1I
Except for the following points, a biomedical adhesive membrane according to Example 1I and a laminate according to Example 1I were produced in the same manner as Example 1A. Instead of the polyoxyethylene (4) (6) sorbitan monooleate aqueous solution, a PEG / PPG-20 / 22 butyl ether dimethicone (HLB value: 7.0) aqueous solution was used. The dipping conditions were adjusted so that the ratio of the mass of PEG / PPG-20 / 22 butyl ether dimethicone contained in the bioadhesive membrane to the mass of the bioadhesive membrane was 20%. The mass of PEG / PPG-20 / 22 butyl ether dimethicone contained in the membrane for biopsy was determined according to the method described in Example 1A.

(Example 1J)
Except for the following points, a biological adhesive film according to Example 1J and a laminate according to Example 1J were produced in the same manner as Example 1A. Instead of the polyoxyethylene (4) (6) sorbitan monooleate aqueous solution, a PEG-9 methyl ether dimethicone (HLB value: 4.5) aqueous solution was used. The dipping conditions were adjusted so that the ratio of the mass of PEG-9 methyl ether dimethicone contained in the bioadhesive membrane to the mass of the bioadhesive membrane was 20%. The mass of PEG-9 methyl ether dimethicone contained in the biomedical patch membrane was determined according to the method described in Example 1A.

(Comparative Example 1A)
Except that the washed polymer gel sheet was dried as it was without being immersed in the polyoxyethylene (4) (6) sorbitan monooleate aqueous solution, the membrane for bioadhesive according to Comparative Example 1A and A laminate according to Comparative Example 1A was produced.

(Comparative Example 2A)
Except for the following points, a biological adhesive film according to Comparative Example 2A and a laminate according to Comparative Example 2A were produced in the same manner as Example 1A. Instead of the polyoxyethylene (4) (6) sorbitan monooleate aqueous solution, a sorbitan tristearate (HLB value: 2.1) aqueous solution was used. The dipping conditions were adjusted so that the ratio of the mass of sorbitan tristearate contained in the bioadhesive membrane to the mass of the bioadhesive membrane was 20%. The mass of sorbitan tristearate contained in the membrane for living body application was determined according to the method described in Example 1A.

(Comparative Example 2B)
Except for the following points, a biological adhesive film according to Comparative Example 2B and a laminate according to Comparative Example 2B were produced in the same manner as Example 1A. Instead of the polyoxyethylene (4) (6) sorbitan monooleate aqueous solution, an aqueous solution of polyethylene glycol distearate (140 EO) (HLB value: 18.9) was used. The immersion conditions were adjusted so that the ratio of the mass of polyethylene glycol distearate (140 EO) contained in the bioadhesive membrane to the mass of the bioadhesive membrane was 20%. The mass of the polyethylene glycol distearate (140 EO) contained in the membrane for biomedical application was determined according to the method described in Example 1A.

(Comparative Example 3A)
Polylactic acid having a weight average molecular weight of 250,000 was dissolved in chloroform to prepare a polylactic acid chloroform solution (polylactic acid concentration: 2.4 mass%). On a substrate having a surface formed of polyvinyl alcohol having a weight average molecular weight of about 500, a chloroform solution of polylactic acid was applied by spin coating to form a coating film. Chloroform was volatilized from this coating film to form a polylactic acid sheet. Thereafter, the polylactic acid sheet was immersed in water to dissolve the polyvinyl alcohol, and the water adhering to the polylactic acid sheet was dried to prepare a polylactic acid film. The polylactic acid film was immersed in an aqueous solution of polyoxyethylene (4) (6) sorbitan monolaurate, and then the polylactic acid film was dried to obtain a biopaste film according to Comparative Example 3A. The immersion conditions were adjusted so that the ratio of the mass of polyoxyethylene (4) (6) sorbitan monolaurate contained in the biomedical membrane to the mass of the biomedical membrane was 20%. The bioadhesive film according to Comparative Example 3A was laminated on the nonwoven fabric to obtain a laminate according to Comparative Example 3A. The mass of the polyoxyethylene (4) (6) sorbitan monolaurate contained in the membrane for biopsy was determined according to the method described in Example 1A.

(Comparative Example 3B)
Except for the following points, a biological adhesive film according to Comparative Example 3B and a laminate according to Comparative Example 3B were produced in the same manner as Comparative Example 3A. Instead of the polyoxyethylene (4) (6) sorbitan monolaurate aqueous solution, a polyoxyethylene (4) (20) sorbitan monolaurate aqueous solution was used. The immersion conditions were adjusted such that the ratio of the mass of polyoxyethylene (4) (20) sorbitan monolaurate contained in the biomedical membrane to the mass of the biomedical membrane was 20%. The mass of the polyoxyethylene (4) (20) sorbitan monolaurate contained in the biomedical film was determined according to the method described in Example 1A.

(Comparative Example 3C)
Except for the following points, a biological adhesive film according to Comparative Example 3C and a laminate according to Comparative Example 3C were produced in the same manner as Comparative Example 3A. Instead of the polyoxyethylene (4) (6) sorbitan monolaurate aqueous solution, a polyoxyethylene (4) (20) sorbitan monopalmitate aqueous solution was used. The dipping conditions were adjusted so that the ratio of the mass of the polyoxyethylene (4) (20) sorbitan monopalmitate contained in the bioadhesive membrane to the mass of the bioadhesive membrane was 20%. The mass of the polyoxyethylene (4) (20) sorbitan monopalmitate contained in the biomedical film was determined according to the method described in Example 1A.

(Comparative Example 3D)
Except for the following points, a biomedical adhesive membrane according to Comparative Example 3D and a laminate according to Comparative Example 3D were produced in the same manner as Comparative Example 3A. Instead of the polyoxyethylene (4) (6) sorbitan monolaurate aqueous solution, a polyoxyethylene (4) (20) sorbitan monostearate aqueous solution was used. The dipping conditions were adjusted so that the ratio of the mass of the polyoxyethylene (4) (20) sorbitan monostearate contained in the bioadhesive membrane to the mass of the bioadhesive membrane was 20%. The mass of the polyoxyethylene (4) (20) sorbitan monostearate contained in the biomedical membrane was determined according to the method described in Example 1A.

(Comparative Example 3E)
Except for the following points, a biomedical adhesive film according to Comparative Example 3E and a laminate according to Comparative Example 3E were produced in the same manner as Comparative Example 3A. Instead of the polyoxyethylene (4) (6) sorbitan monolaurate aqueous solution, a bisPEG-18 methyl ether dimethylsilane aqueous solution was used. The immersion conditions were adjusted so that the ratio of the mass of bisPEG-18 methyl ether dimethylsilane contained in the bioadhesive membrane to the mass of the bioadhesive membrane was 20%. The mass of bisPEG-18 methyl ether dimethyl silane contained in the biopaste membrane was determined according to the method described in Example 1A.

(Example 2A)
Except for the points described below, a membrane for biological application according to Example 2A and a laminate according to Example 2A were produced in the same manner as Example 1A. Instead of the polyoxyethylene (4) (6) sorbitan monooleate aqueous solution, a polyoxyethylene (4) (20) sorbitan monostearate aqueous solution was used. The immersion conditions were adjusted such that the ratio of the mass of polyoxyethylene (4) (20) sorbitan monostearate contained in the biomedical membrane to the mass of the biomedical membrane was 15%. The mass of the polyoxyethylene (4) (20) sorbitan monostearate contained in the biomedical membrane was determined according to the method described in Example 1A.

(Example 2B)
Except for the following points, a biomedical adhesive membrane according to Example 2B and a laminate according to Example 2B were produced in the same manner as Example 1A. Instead of the polyoxyethylene (4) (6) sorbitan monooleate aqueous solution, a polyoxyethylene (4) (20) sorbitan monostearate aqueous solution was used. The dipping conditions were adjusted so that the ratio of the mass of polyoxyethylene (4) (20) sorbitan monostearate contained in the biomedical membrane to the mass of the biomedical membrane was 10%. The mass of the polyoxyethylene (4) (20) sorbitan monostearate contained in the biomedical membrane was determined according to the method described in Example 1A.

(Example 3A)
Except for the following points, a biomedical adhesive membrane according to Example 3A and a laminate according to Example 3A were produced in the same manner as Example 1A. Instead of the polyoxyethylene (4) (6) sorbitan monooleate aqueous solution, a bisPEG-18 methyl ether dimethylsilane aqueous solution was used. The dipping conditions were adjusted so that the ratio of the mass of bisPEG-18 methyl ether dimethylsilane contained in the bioadhesive membrane to the mass of the bioadhesive membrane was 15%. The mass of bisPEG-18 methyl ether dimethyl silane contained in the biopaste membrane was determined according to the method described in Example 1A.

(Example 3B)
Except for the following points, a biomedical adhesive membrane according to Example 3A and a laminate according to Example 3A were produced in the same manner as Example 1A. Instead of the polyoxyethylene (4) (6) sorbitan monooleate aqueous solution, a bisPEG-18 methyl ether dimethylsilane aqueous solution was used. The dipping conditions were adjusted so that the ratio of the mass of bisPEG-18 methyl ether dimethylsilane contained in the bioadhesive membrane to the mass of the bioadhesive membrane was 10%. The mass of bisPEG-18 methyl ether dimethyl silane contained in the biopaste membrane was determined according to the method described in Example 1A.

(Example 4A)
Except for the following points, a biomedical adhesive membrane according to Example 4A and a laminate according to Example 4A were produced in the same manner as Example 1A. Instead of the polyoxyethylene (4) (6) sorbitan monooleate aqueous solution, a PEG-9 dimethicone aqueous solution was used. The dipping conditions were adjusted so that the ratio of the mass of PEG-9 dimethicone contained in the bioadhesive membrane to the mass of the bioadhesive membrane was 15%. The mass of PEG-9 dimethicone contained in the membrane for biopsy was determined according to the method described in Example 1A.

(Example 4B)
Except for the following points, a biomedical adhesive membrane according to Example 4B and a laminate according to Example 4B were produced in the same manner as Example 1A. Instead of the polyoxyethylene (4) (6) sorbitan monooleate aqueous solution, a PEG-9 dimethicone aqueous solution was used. The dipping conditions were adjusted so that the ratio of the mass of PEG-9 dimethicone contained in the bioadhesive membrane to the mass of the bioadhesive membrane was 10%. The mass of PEG-9 dimethicone contained in the membrane for biopsy was determined according to the method described in Example 1A.

Tables 1 and 2 show the results (wearing time) of the wearing test on the biomedical adhesive membranes according to each example and each comparative example. In all of the examples, it was confirmed that it can be continuously mounted for at least 30 minutes after mounting. When Examples 1A to 1J were compared with Comparative Example 1A, polyoxyethylene (4) (6) sorbitan monooleate, polyoxyethylene (4) (6) sorbitan monolaurate, polyoxyethylene (4) (20 ) Sorbitan monolaurate, polyoxyethylene (4) (20) sorbitan monopalmitate, polyoxyethylene (4) (20) sorbitan monostearate, bisPEG-18 methyl ether dimethylsilane, PEG-11 methyl ether dimethicone, Including PEG-9 dimethicone, PEG / PPG-20 / 22 butyl ether dimethicone, or PEG-9 methyl ether dimethicone has been shown to dramatically reduce the mounting time of the biomedical membrane. From the result of Comparative Example 2A, even when sorbitan tristearate having an HLB value of 2.1 was included, it was not possible to shorten the wearing time of the bioadhesive membrane. From the result of Comparative Example 2B, even when polyethylene glycol distearate (140 E.O.) having an HLB value of 18.9 was included, the wearing time of the bioadhesive membrane could not be shortened. According to Comparative Examples 3A to 3E, even when using a polylactic acid film containing a component having an HLB value of 13.3, 14.9, 15.6, 16.7, or 17.8, Installation time could not be shortened. From the above, it was shown that the bioadhesive membrane containing the regenerated cellulose and the additive having an HLB value of 4 to 18 can be applied to the skin in a short time.

According to Table 2, it was shown that when the biomedical adhesive membrane contains 10% by mass or more of polyoxyethylene (4) (20) sorbitan monostearate, the wearing time of the bioadhesive membrane can be dramatically shortened. . In addition, it has been shown that when the bioadhesive membrane contains 10% by mass or more of bisPEG-18 methyl ether dimethylsilane, the wearing time of the bioadhesive membrane can be dramatically shortened. Furthermore, it was shown that when the bioadhesive membrane contains 10 mass% or more of PEG-9 dimethicone, the wearing time of the bioadhesive membrane can be dramatically shortened. From the above, it was shown that when the concentration of the additive having an HLB value of 4 to 18 in the biomedical adhesive film is 10% by mass or more, the bioadhesive film can be applied to the skin in a short time.

DESCRIPTION OF SYMBOLS 10 Membrane for biological sticking 11 1st main surface 12 2nd main surface 21 1st protective layer 22 2nd

protective layer

50a, 50b Laminate

Claims

Regenerated cellulose, and an accelerator that promotes attachment of the regenerated cellulose to a living tissue,
A self-supporting type having a thickness of 20 to 5000 nm,
The accelerator has an HLB value of 4 to 18,
Membrane for living body application.
The membrane for bioadhesion according to claim 1, wherein the regenerated cellulose has a weight average molecular weight of 30,000 or more.
The membrane for bioadhesion according to claim 1 or 2, having a thickness of 20 to 1300 nm.
The membrane for bioadhesion according to any one of claims 1 to 3, wherein the regenerated cellulose has a weight average molecular weight of 150,000 or more.
The bio-adhesive membrane according to any one of claims 1 to 4, wherein the accelerator is a compound having an ethylene glycol chain or a polyethylene glycol chain.
The accelerator is at least one selected from the group consisting of a compound represented by the following formula (A), a compound represented by the following (B), and a compound represented by the following (C). 6. The membrane for biological application according to any one of 1 to 5.

In formulas (A), (B), and (C), each of a, b, c, d, and e is an integer of 0 or more, and at least one of a and b is an integer of 1 or more, c , D, and e are each an integer of 1 or more, f is an integer of 1 or more, and R 1 and R 2 are each independently an alkyl group, an alkoxy group, (poly) ethylene glycol (alkyl Ether) group or (poly) propylene glycol group.
The membrane for biological application according to any one of claims 1 to 6, wherein the content of the accelerator in the membrane for biological application is 10 to 90% by weight.
Examples of the accelerator include bisPEG-18 methyl ether dimethylsilane, polyoxyethylene (4) (6) sorbitan monooleate, polyoxyethylene (4) (6) sorbitan monolaurate, polyoxyethylene (4) (20 ) Sorbitan monolaurate, polyoxyethylene (4) (20) sorbitan monopalmitate, polyoxyethylene (4) (20) sorbitan monostearate, PEG-11 methyl ether dimethicone, PEG-9 dimethicone, PEG-9 methyl The membrane for bioadhesion according to any one of claims 1 to 7, which is at least one selected from the group consisting of ether dimethicone and PEG / PPG-20 / 22 butyl ether dimethicone.
A cosmetic method for affixing a membrane for bioadhesion,
The membrane for bioadhesion includes a regenerated cellulose and a promoter having an HLB value of 4 to 18 that promotes the attachment of the regenerated cellulose to a living tissue, and has a thickness of 20 to 5000 nm. And
Attaching a mounting agent containing an oily component to a living tissue and the membrane for attaching a living body, and attaching the membrane for attaching a living body to the living tissue,
Beauty method.
The cosmetic method according to claim 9, wherein the oil component is at least one selected from the group consisting of fatty acids, paraffins, naphthenes, cycloparaffins, and silicone oils.