JP7170231B2 - Adhesive film for living body, laminate, and cosmetic method - Google Patents

Description

TECHNICAL FIELD The present disclosure relates to a biological adhesive film, a laminate, and a cosmetic method.

2. Description of the Related Art Conventionally, bioadhesive films that are attached to biomedical tissues such as skin are known.

For example, Patent Document 1 describes a beauty method that is excellent in the so-called secondary adhesion-less effect, in which a large amount of a coloring material such as a pigment is blended, and a cosmetic such as a foundation does not adhere to clothes or the like. Also described are thin films for use in This thin film consists 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.

Patent Literature 2 describes a self-supporting cosmetic sheet that is used in a predetermined makeup method and applied to the skin. This self-supporting cosmetic sheet comprises at least one biocompatible and/or biodegradable hydrophobic polymer layer. Biocompatible and/or biodegradable polymers are, for example, non-crosslinked polymers such as non-crosslinked polylactic acid. The hydrophobic polymer layer includes, for example, at least one cationic polymer and at least one anionic polymer.

International Publication No. 2014/058060 Japanese Patent Publication No. 2015-512863

In the techniques described in Patent Literatures 1 and 2, no study has been made on the adhesiveness of the bioadhesive film containing regenerated cellulose to the living tissue. Accordingly, the present disclosure provides a film for biological patch that contains regenerated cellulose and has high adhesiveness to biological tissue.

This disclosure is
Containing regenerated cellulose and an adhesive component attached to the regenerated cellulose,
is self-supporting with a thickness of 20 to 6500 nm,
The adhesive component contains a polyamino acid,
A bioadhesive film is provided.

Additional effects and advantages of the disclosed embodiments will become apparent from the specification and drawings. Benefits 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 bioadhesive film described above contains regenerated cellulose and has high adhesion to living tissue.

FIG. 1A is a cross-sectional view schematically showing an example of the laminate of the present disclosure. FIG. 1B is a cross-sectional view schematically showing an example of the positional relationship between the regenerated cellulose and the adhesive component in the biological adhesive membrane of the present disclosure. FIG. 2A is a diagram showing a method of using the bioadhesive film of the present disclosure. FIG. 2B is a diagram showing a method of using the bioadhesive film of the present disclosure. FIG. 2C is a diagram showing a method of using the bioadhesive film of the present disclosure. FIG. 3 is a cross-sectional view schematically showing another example of the laminate of the present disclosure.

(Findings on which this disclosure is based)
The present inventors have developed a self-supporting bioadhesive membrane with a thickness of several μm or less composed of regenerated cellulose, which has not been realized in the past. The inventors of the present invention made further studies on this film for use on a living body, and found that there was room for improvement from the viewpoint of adhesion to living tissue. Therefore, the present inventors repeated a great deal of trial and error in order to increase the adhesiveness of the biological adhesive film to the biological tissue. As a result, the present inventors have newly found that the adhesiveness of the bioadhesive film to the living tissue is enhanced by attaching a predetermined adhesive component to the regenerated cellulose in the bioadhesive film. Based on this new knowledge, the present inventors devised the membrane for bioadhesion according to the present disclosure.

A summary of aspects of the disclosure follows.

(Item 1)
Containing regenerated cellulose and an adhesive component attached to the regenerated cellulose,
is self-supporting with a thickness of 20 to 6500 nm,
The adhesive component contains a polyamino acid,
A film to be attached to a living body.

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

(Item 3)
3. The organism according to item 1 or 2, wherein the polyamino acid has at least one functional group selected from the group consisting of a hydroxyl group, an aldehyde group, a carboxyl group, an amino group, a guanidino group, and a carbonyl group in the repeating structural unit. Sticking membrane.

(Item 4)
The adhesive component contains one or more polyamino acids selected from the group consisting of polyglutamic acid, polytyrosine, polylysine, polyarginine, polyornithine, polyaspartic acid, polyhistidine, and salts thereof. 4. The bioadhesive film according to any one of 1 to 3.

(Item 5)
The biological adhesive membrane according to any one of items 1 to 4, wherein at least part of the adhesive component is present on the surface of the biological adhesive membrane.

(Item 6)
The biological patch according to any one of items 1 to 5, wherein at least part of the adhesive component is present continuously between the surface of the biological patch and the regenerated cellulose in the thickness direction. film.

(Item 7)
The biological adhesive membrane according to any one of items 1 to 6, wherein the content of the adhesive component in the biological adhesive membrane is 0.05 to 50% by weight.

(Item 8)
The biological patch according to any one of items 1 to 7, wherein the polyamino acid has a weight average molecular weight of 10,000 or more.

(Item 9)
a biological patch film according to any one of items 1 to 8;
a first protective layer disposed on the first main surface of the biological adhesive membrane and removable from the first main surface;
laminate.

(Item 10)
10. The laminate according to item 9, further comprising a second protective layer disposed on the second main surface of the membrane for adhesive application to a living body, which is located on the opposite side of the first main surface.

(Item 11)
A cosmetic method for attaching a film to be attached to a living body, comprising:
The bioadhesive membrane comprises regenerated cellulose and an adhesive component containing a polyamino acid attached to the regenerated cellulose, and is self-supporting and has a thickness of 20 to 6500 nm,
attaching a water-containing adhesive to a biological tissue and the biological adhesive film, and attaching the biological adhesive film to the biological tissue;
beauty method.

(embodiment)
Hereinafter, embodiments of the present disclosure will be described with reference to the drawings. In addition, the following embodiments are merely examples, and the biological adhesive membrane of the present disclosure is not limited to the following embodiments. Matters such as numerical values, shapes, materials, components, arrangement of components, connection forms, and steps and the order of steps shown in the following embodiments are examples and are intended to limit the present disclosure. It's not something. The following various embodiments can be combined with each other unless inconsistent. In addition, among the constituent elements in the following embodiments, constituent elements that are not described in independent claims indicating the highest concept should not be understood as essential constituent elements. In the following description, constituent elements having substantially the same functions are denoted by common reference numerals, and their description may be omitted. Also, some elements may be omitted to avoid over-complicating the drawings.

The bioadhesive film 10 shown in FIG. 1A contains regenerated cellulose and an adhesive component. The adhesive component adheres to the regenerated cellulose. Regenerated cellulose typically forms the skeleton (base material) of the biological patch 10 . The bioadhesive membrane 10 is a self-supporting membrane having a thickness of 20 to 6500 nm. As used herein, "self-supporting membrane" means a membrane that can maintain its morphology without a support. For example, when the self-supporting membrane is lifted by pinching a portion of the self-supporting membrane using fingers or tweezers, the self-supporting membrane can be formed without the support without damaging the self-supporting membrane. can be lifted in its entirety. The adhesive component contains polyamino acids.

Regenerated cellulose is rich in hydroxyl groups in its repeating structure. For this reason, it is considered that the polyamino acid contained in the adhesive component and the regenerated cellulose interact with each other so as to attract each other through hydrogen bonding. For this reason, the adhesive component appropriately adheres to the cellulose in the biological adhesive film 10 . In addition, it is considered difficult to use polyamino acid as an adhesive component for the base film made of polylactic acid described in Patent Document 1. This is because the repeating structure of polylactic acid has no functional group capable of forming a hydrogen bond, and polylactic acid exhibits hydrophobicity. Hydrophilic polyamino acids and hydrophobic polylactic acids are unlikely to interact with each other, and polyamino acids are considered unsuitable as adhesive components in polylactic acid base films.

The outermost surface of living tissue such as skin is mainly composed of proteins such as keratin. Proteins are composed of amide bonds. Therefore, when the biological adhesive film 10 is attached to a biological tissue, a hydrogen bond is formed between the amide bond of the polyamino acid and the amide bond of the protein, and the biological adhesive film 10 has a high resistance to the biological tissue. Adhesion can be exhibited.

The adhesive component contains polyamino acids and has biocompatibility. Biocompatibility means the property that the material hardly causes harmful phenomena to the living body such as stuffiness and feeling of heat when it is brought into contact with the living tissue.

Polyamino acids are, for example, homopolymers of amino acids. In this case, polyamino acids tend to have less intramolecular interaction due to the effects of charge and hydrophilicity or hydrophobicity. Therefore, polyamino acids are less likely to be folded and more likely to have a uniform structure, as compared to proteins or peptides in which various amino acids are arranged. As a result, in polyamino acids, interactable sites tend to appear outside and interact with living tissue or regenerated cellulose. As a result, the adhesiveness of the biological adhesive film 10 to the biological tissue increases more reliably.

Polyamino acids are typically water soluble. In this case, the biological adhesive film 10 can be easily peeled off from the biological tissue using an aqueous solution or the like, and the biological adhesive film 10 hardly remains in the living organism. Incidentally, even if the biological adhesive film 10 remains in the biological body, the biological adhesive film 10 has biocompatibility, so it is unlikely to cause problems in the biological body.

Amino acids that form polyamino acids can be in the L-, D-, or racemic form. Amino acids forming polyamino acids are desirably in the L configuration. In living organisms, mainly L-form amino acids are present. Therefore, if for some reason polyamino acids are percutaneously absorbed and decomposed into compounds such as amino acids, the biological patch 10 will be safer if the polyamino acids contained in the adhesive components are L-forms. be.

A polyamino acid has, for example, at least one functional group selected from the group consisting of a hydroxyl group, an aldehyde group, a carboxyl group, an amino group, a guanidino group, and a carbonyl group in a repeating structural unit. In this case, these functional groups form many hydrogen bonds between proteins such as keratin in biological tissue or regenerated cellulose and polyamino acids, thereby increasing the adhesiveness of the biological patch 10 to biological tissue.

Examples of adhesive components include polyglutamic acid, polytyrosine, polylysine, polyarginine, polyornithine, polyaspartic acid, polyhistidine, polyserine, polyhydroxyproline, polyhydroxylysine, polyglycine, polyalanine, polycysteine, polyisoleucine, poly from the group consisting of leucine, polymethionine, polyphenylalanine, polyproline, polytryptophan, polyvaline, polythyroxine, polyphosphoserine, poly-β-alanine, poly-γ-aminobutyric acid, polycreatine, polycitrulline, and salts thereof It contains at least one or more selected polyamino acids.

The adhesive component desirably contains at least one or more polyamino acids selected from the group consisting of polyglutamic acid, polytyrosine, polylysine, polyarginine, polyornithine, polyaspartic acid, polyhistidine, and salts thereof. there is

In the biological adhesive membrane 10 of the present disclosure, "the adhesive component is attached to the regenerated cellulose" typically means that at least part of the adhesive ingredient is present on the surface of the biological adhesive membrane 10. Indicates status. However, the state in which the adhesive component is present so as to be in contact with the surface of the biological patch 10 is also included in the scope of "the adhesive component adheres to the regenerated cellulose". In addition, the state in which the adhesive component can be eluted to the surface by attaching the membrane 10 for application to a living body or the like is also included in the scope of "the adhesive component is adhered to the regenerated cellulose". For example, part of the adhesive component in the film 10 for biological application exists on the surface of the film 10 for biological application. Therefore, the adhesive component is likely to interact with both the regenerated cellulose and the biological tissue, and the adhesiveness of the biological adhesive film 10 to the biological tissue is further increased. In addition, at least part of the adhesive component desirably exists continuously between the surface of the biological adhesive film 10 and the regenerated cellulose in the thickness direction of the biological adhesive film 10 . In this case, the adhesive component polyamino acid can form a hydrogen bond with the regenerated cellulose at a position away from the surface of the biological patch 10, which is useful.

The adhesive component in the membrane 10 to be patched to a living body may be uniformly distributed in the thickness direction of the membrane 10 to be patched to a living body. The adhesive component may be concentrated at a specific location in the membrane 10 to be applied to a living body. For example, in the biological adhesive membrane 10, a plurality of regions in which the adhesive component exists at a high concentration may exist at predetermined intervals. The adhesive component may be present in layers on the surface of the membrane 10 for biological patch. In this case, the layer of the adhesive component may cover the entire substrate composed of regenerated cellulose, or may cover a portion of the substrate.

FIG. 1B shows an example of the positional relationship between the regenerated cellulose 13 and the adhesive component 14 in the biological patch 10 . As shown in FIG. 1B , in the biological adhesive film 10 , part of the adhesive component 14 exists on the surface of the biological adhesive film 10 . In this case, the adhesive component 14 may be in contact with the surface of the regenerated cellulose 13 . Desirably, part of the adhesive component 14 exists continuously from the inside of the regenerated cellulose 13 to the surface of the biological adhesive membrane 10 in the thickness direction of the biological adhesive membrane 10 . The physical shape formed by the adhesive component 14 in the biological adhesive film 10 is not limited to a specific three-dimensional shape. The shape is desirably such that the contact area between the regenerated cellulose 13 and the adhesive component 14 is as large as possible. This enhances the adhesive effect of the adhesive component 14 . The adhesive component 14 may be present continuously from one surface (principal surface) of the biological adhesive membrane 10 to the other surface (principal surface). A part of the adhesive component 14 may not exist on the surface of the biological adhesive membrane 10 and may exist only inside the regenerated cellulose 13 . In addition, the positional relationship between the regenerated cellulose 13 and the adhesive component 14 is not limited to the state shown in FIG. 1B as long as the adhesive component 14 adheres to the regenerated cellulose 13 .

The content of the adhesive component in the biological adhesive film 10 is, for example, 0.05 to 50% by weight. In this case, the biological adhesive film 10 can more reliably exhibit high adhesion to the biological tissue. When the content of the adhesive component in the biological-adhesive film 10 is 50% by weight or less, stickiness of the biological-adhesive film 10 is suppressed, and the biological-adhesive film 10 is easily adhered to the living body.

The ratio of the weight of the sticky component to the weight of the regenerated cellulose is, for example, 0.05-90%, and can be 0.05-50%.

The polyamino acid of the adhesive component has, for example, a weight average molecular weight of 10,000 or more. In this case, the viscosity of the polyamino acid increases, and the adhesiveness of the biological patch 10 to the biological tissue increases more reliably. Polyamino acids, for example, have weight average molecular weights of 10,000 to 10,000,000. Polyamino acids may have a weight average molecular weight of 10,000 to 2,000,000. When the polyamino acid has a weight average molecular weight of 2,000,000 or less, the adhesive component can be easily attached to the regenerated cellulose. The weight average molecular weight of polyamino acids can be determined, for example, by gel permeation chromatography (GPC). A sample for GPC measurement can be prepared by, for example, dissolving a commercially available reagent or the like, extracting from a commercially available cosmetic material or drug, or extracting a polyamino acid, which is an adhesive component, from the bioadhesive membrane 10. . For example, when extracting the adhesive component from the biological adhesive membrane 10, the biological adhesive membrane 10 is immersed in a solution described later, and only polyamino acids are added to the solution by stirring, shaking, ultrasonic treatment, heating, or the like. can be extracted. The solution is, for example, water, methanol, ethanol, or a highly water-soluble solvent such as acetic acid.

In regenerated cellulose, intramolecular and/or intermolecular hydrogen bonds are likely to be formed, and the biological patch 10 is likely to have a dense structure. For this reason, membranes derived from regenerated cellulose tend to retain their shape more easily than membranes derived from natural cellulose nanofibers. Furthermore, since cellulose exhibits amphiphilicity, it can appropriately support a hydrophilic active ingredient and a hydrophobic active ingredient, and the bioadhesive membrane 10 has high versatility.

The raw material for regenerated cellulose is not particularly limited. For example, the raw material of the regenerated cellulose may be plant-derived natural cellulose, biological-derived natural cellulose, regenerated cellulose such as cellophane, or processed cellulose such as cellulose nanofiber. Advantageously, 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, "cellulose substantially represented by formula (I)" means cellulose in which 90% or more of hydroxyl groups of glucose residues in cellulose represented by formula (I) remain. The ratio of the number of hydroxyl groups of glucose residues in the cellulose contained in the biological patch 10 to the number of hydroxyl groups of glucose residues in the cellulose represented by formula (I) is, for example, X-ray photoelectron spectroscopy (XPS ) can be quantified by a known method such as In some cases, the regenerated cellulose contained in the biological patch 10 may contain a branched structure. Artificially derivatized cellulose typically does not fall under "cellulose substantially represented by formula (I)". On the other hand, "cellulose substantially represented by formula (I)" does not exclude cellulose regenerated through derivatization. Even cellulose regenerated through derivatization may correspond to "cellulose substantially represented by formula (I)".

In the embodiment of the present disclosure, the biological adhesive membrane 10 is composed of regenerated cellulose. The strength of a film formed from a suspension of natural cellulose fibers in water or the like is due to hydrogen bonding between nanofibers that make up the cellulose fibers. Therefore, only brittle cellulose membranes are obtained. In contrast, in membranes made of regenerated cellulose, the nanofibers are loosened to the molecular chain level, so the strength of the membrane made of regenerated cellulose is due to the hydrogen bonds between the cellulose molecular chains. . That is, in a membrane composed of regenerated cellulose, hydrogen bonds are uniformly formed between units smaller than nanofibers. Therefore, compared with the case where the film is formed from a suspension in which natural cellulose fibers are dispersed in water, etc., it is possible to provide a cellulose film that is less fragile, has appropriate flexibility, and is hard to tear. can do. Here, “nanofiber” is also called “nanofibril (or microfibril)”, and is the most basic unit in which cellulose molecules aggregate, and has a width of about 4 nm to about 100 nm, for example, about 1 μm. or longer.

As used herein, "regenerated cellulose" means cellulose that does not have the crystalline structure I characteristic of natural cellulose. The crystal structure of cellulose can be confirmed by an XRD pattern. In the XRD pattern of natural cellulose using CuKα rays, peaks around 14-17° and 23° unique to crystal structure I appear, but regenerated cellulose often has crystal structure II, at 12° and 20°. , and 22° and no peaks around 14-17° and 23°.

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

The cellulose contained in the biological patch 10 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 adhesiveness of the film 10 for biological patch to the living body tends to be high. By performing predetermined chemical modification at sites where hydroxyl groups should exist, the membrane 10 for biological patch can exhibit various functions.

The crystallinity of the cellulose contained in the biological patch ¹⁰ is reported, for example, in Park et al. "Cellulose crystallinity index: measurement techniques and their impact on interpreting cellulase performance" Biotechnology for Biofuels 2010, 310 - can be determined by NMR-based techniques; According to this method, in the spectrum obtained by solid-state ¹³ C-NMR measurement, the peak near 87 to 93 ppm is considered to be derived from the crystal structure, and the broad peak near 80 to 87 ppm is considered to be derived from the non-crystalline structure. The crystallinity is determined by the following formula, where X is the peak area of and Y is the peak area of the latter. In the formula below, "x" represents multiplication.
(Crystallinity)% = (X/(X + Y)) x 100

As described above, the biological adhesive film 10 has a thickness of 20 to 6500 nm. If the thickness of the biological adhesive film 10 is 20 nm or more, the biological adhesive film 10 can function as a self-supporting membrane that can be attached to a biological tissue. If the thickness of the biological adhesive film 10 is 6500 nm or less, the biological adhesive film 10 is less likely to peel off due to friction, stress from the skin, or the like when the biological adhesive film 10 is attached to a biological tissue. On the other hand, the biological adhesive film 10 can be easily peeled off from the biological tissue using an aqueous solution or the like. The thickness of the membrane 10 to be patched to a living body is determined by, for example, measuring the thickness of the membrane 10 to be patched to a living body at a plurality of points and averaging the measured thicknesses. The thickness at each location can be measured, for example, using a stylus profiling system DEKTAK (registered trademark) manufactured by Bruker Nano Inc.

The thickness of the biological patch 10 may be 100 nm or more. When the thickness of the film 10 for sticking to a living body is 100 nm or more, the strength of the film 10 for sticking to a living body increases, and the film 10 for sticking to a living body is easy to handle. The thickness of the biological patch 10 may be 300 nm or more. When the thickness of the membrane 10 for sticking to a living body is 300 nm or more, the strength of the membrane 10 for sticking to a living body increases, and the membrane 10 for sticking to a living body 10 is hard to break and can be used easily. The thickness of the biological patch 10 may be 500 nm or more. When the thickness of the biological patch 10 is 500 nm or more, the biological patch 10 can hold more active ingredients such as cosmetic ingredients. The thickness of the biological patch 10 may be 2000 nm or less. When the thickness of the biological adhesive film 10 is 2000 nm or less, the adhesiveness of the biological adhesive film 10 to the biological tissue is high, and the biological adhesive film 10 can be stably attached to the surface of the biological tissue such as the skin. can. The thickness of the biological patch 10 may be 1300 nm or less. When the thickness of the biological adhesive film 10 is 1300 nm or less, the adhesiveness of the biological adhesive film 10 to the biological tissue is higher, and the biological adhesive film 10 can be stably attached to the surface of the biological tissue such as the skin for a long time. can be maintained.

The shape of the biological adhesive film 10 is not particularly limited when the biological adhesive film 10 is viewed from above. The biological adhesive film 10 may be circular, elliptical, or polygonal in plan view. The biological adhesive film 10 may have an irregular shape in plan view.

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

In the case of cosmetic applications, the biological adhesive film 10 is used for, for example, (i) skin care such as whitening, moisturizing, and wrinkle prevention, (ii) hair care such as hair growth, hair thickening, depilation, and hair styling, or (iii)
) Used for make-up such as foundation, face powder, and nail art. In the case of medical use, the biological adhesive film 10 is used, for example, to administer drugs such as analgesic anti-inflammatory drugs, anti-inflammatory drugs, cardiotonic drugs, antifungal drugs, adrenocortical hormone drugs, and blood circulation promoting drugs to the living body. good too.

The biological adhesive film 10 may contain components other than the regenerated cellulose and the adhesive component. For example, the biological adhesive film 10 may contain a predetermined active ingredient. The active ingredient can be, for example, a whitening ingredient, an ultraviolet protective ingredient, a moisturizing ingredient, a hair-restoring ingredient, and a cosmetic ingredient or medicinal ingredient such as cosmetics. Cosmetic ingredients include, for example, gum arabic, tragacanth gum, galactan, guar gum, carob gum, karaya gum, carrageenan, pectin, agar, quince seed (quince), algecolloid (cassou extract), starch (rice, corn, potato, wheat), succino glucan, casein, albumin, gelatin, mucin, chondroitin sulfate, xylitol, maltitose, sodium pyrrolidone carboxylate, retinol, retinal, and vitamin A such as retinoic acid; vitamin B, such as thiamine, riboflavin, pyridoxine, pyridoxamine, and folic acid; ascorbic vitamin C such as acid (sodium), vitamin D such as ergocalciferol and cholecalciferol, vitamin E such as α-tocopherol, vitamin K such as phylloquinone and menaquinone, vitamin A derivatives such as tretinoin and retinol palmitate, fursulfur vitamin B derivatives such as thiamine; vitamin C derivatives such as glyceryl ascorbic acid and ascorbyl tetrahexyldecanoate; vitamin D derivatives such as dihydrotachysterol; E derivatives, hydroquinone, potassium 4-methoxysalicylate, rucinol, polyphenols such as anthocyanins, disodium 3-succinyloxyglycyrrhetinate, placenta, dioxybenzone, 2-ethylhexyl 4-methoxycinnamate, various amino acids, keratin, hydroxyapatite, Ceramics such as tricalcium phosphate, calcium carbonate, alumina, zirconia, 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 pigment, dye, phenoxyethanol, fullerene, astaxanthin, coenzyme, human oligopeptide, glycerin, diglycerin, sorbitol, Pyrrolidone carboxylic acid, fatty acid polyglyceryl, polyglycerin, jojoba oil, trimethylglycine, mannitol, trehalose, glycosyltrehalose, pullulan, erythritol, elastin, dipro pyrene glycol, butylene glycol, ethyl ethylhexanoate, sodium acrylate, disodium edetate, sucrose fatty acid ester, squalane, polyethylene glycol, polyoxyethylene hydrogenated castor oil, glycerin stearate, ethanol, polyvinyl alcohol, hydroxyethyl cellulose, or Ectoine. Medicinal ingredients include, for example, cepharanthine, rutin, isosorbide nitrate, indomethacin, diflucortolone valerate, acyclovir, ketoconazole, ketoprofen, diclofenac sodium, dexamethasone propionate, felbinac, clobetasol propionate, loxoprofen, methyl salicylate, or tacrolimus. is. These active ingredients can be contained in the bioadhesive film 10 in the form of solids, solutions, dispersions, or emulsions.

At least part of the membrane 10 to be applied to a living body may be colored. For example, at least a portion of the biological patch 10 may be colored in a color close to the color of the skin. In this case, stains, moles, and scars on the skin can be covered with the membrane 10 to be applied to a living body to make them inconspicuous.

The bioadhesive film 10 is used by being attached to the skin, for example, on the face and arms. Therefore, the biological patch 10 typically has an area of 7 mm ² or more. Thereby, a wide area can be covered when the biological patch film 10 is attached to the skin. In addition, the biological adhesive film 10 may be attached to the surface of a biological tissue other than the skin, such as an organ. The organ can be protected by attaching the film 10 for living body patch to the surface of the organ. For example, adhesion between organs can be prevented.

As shown in FIG. 1A, the laminate 50a includes a biological adhesive film 10 and a first protective layer 21. As shown in FIG. The biological adhesive film 10 has a first principal surface 11 and a second principal surface 12 . The second main surface 12 is located on the opposite side of the first main surface 11 of the membrane 10 for biological application. The first protective layer 21 is arranged on the first major surface 11 . The first protective layer 21 is a layer removable from the first major surface 11 . The first protective layer 21 is in contact with the first major surface 11, for example.

The first protective layer 21 is made of, 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), aramids, and polyimides, sheets of polymeric materials, wovens, nonwovens, or meshes, (ii) sheet metal, or (iii) sheet glass. All or part of the surface of the first protective layer 21 may be subjected to a chemical or physical surface treatment. In addition, the first protective layer 21 has a shape that is the same as or different from the shape of the membrane 10 to be adhered to a living body, and a size that is the same as or different from the size of the membrane 10 to be stuck to a living body, in plan view. For example, a plurality of bioadhesive membranes 10 may be arranged on a single first protective layer 21 . In addition, the biological adhesive 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 bioadhesive film 10 can maintain its shape.

An example of how to use the laminate 50a will be described. The biological adhesive film 10 is attached, for example, to the skin of the face. The biological adhesive film 10 may be attached to the skin of the arm, or may be attached to a biological tissue other than the skin. As shown in FIG. 2A , for example, the second main surface 12 of the biological adhesive film 10 is directed toward a specific site (for example, skin) of the biological body, and the laminate 50a is brought close to the second main surface 12 of the biological adhesive film 10 . is brought into contact with a specific part of the living body. At this time, a liquid or cream adhesive may be adhered to a specific site of the living body or to the membrane 10 to be applied to the living body. This dressing is, for example, at least one selected from the group consisting of pure water, physiological saline, lotion, aqueous solution such as beauty essence, lotion containing organic solvent, milky lotion, essence, and cream. The dressing includes, for example, water. In this case, since the adhesive component of the biological adhesive film 10 is typically water-soluble, the adhesive component dissolves in water to lower the viscosity and improve the adhesiveness of the biological adhesive film 10 to the skin. The dressing may be an aqueous solution containing a polyhydric alcohol. Polyhydric alcohols in this case are, for example, glycerol or propanediol. Compared to water, these aqueous solutions allow the membrane 10 to be adhered to a living body to be adhered to the skin more easily for a longer period of time. The dressing contains, for example, water, fat, alcohol, or emulsifier, and may further contain one or more active ingredients as described above. The adhesive may adhere to the specific site of the living body or the membrane 10 to be attached to the living body before the second main surface 12 and the specific site of the living body come into contact with each other. You may make it adhere to the film|membrane 10 for a biological patch after contacting with a site|part.

Next, as shown in FIG. 2B, the first protective layer 21 is peeled off from the first main surface 11 of the membrane 10 for biological application. At this time, the biological adhesive film 10 is in close contact with the biological tissue, and the state in which the biological adhesive film 10 is attached to the biological tissue is maintained. When the first protective layer 21 is completely peeled off, the entire first major surface 11 of the biological adhesive membrane 10 is exposed as shown in FIG. 2C.

Laminate 50a may be modified as laminate 50b shown in FIG. The laminate 50b is configured in the same manner as the laminate 50a unless otherwise specified. Components of the laminate 50b that are the same as or correspond to those of the laminate 50a are denoted by the same reference numerals, and detailed description thereof is omitted. The description regarding the laminate 50a also applies to the laminate 50b unless technically contradictory.

As shown in FIG. 3, the laminate 50b further comprises a second protective layer 22. As shown in FIG. A second protective layer 22 is arranged on the second major surface 12 . The second protective layer 22 can protect the second major surface 12 . In addition, the second protective layer 22 facilitates handling of the laminate 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 membrane 10 to be adhered to a living body, and a size that is the same as or different from the size of the membrane 10 to be stuck to a living body, in plan view. The second protective layer 22 has a shape that is the same as or different from the shape of the first protective layer 21 and a size that is the same as or different from the size of the first protective layer 21 in plan view.

Second protective layer 22 is typically removable from second major surface 12 . When using the laminate 50b, for example, first, the second protective layer 22 is peeled off from the membrane 10 for sticking to a living body. Thereby, the second main surface 12 is exposed. After that, the second principal surface 12 is brought close to the specific site of the living body, and the membrane 10 for biological application is attached to the specific site of the living body in the same manner as the laminate 50a.

An example of the manufacturing method of the membrane 10 for living body patch will be described. First, cellulose is dissolved in a solvent to prepare a cellulose solution. In order to obtain a regenerated cellulose membrane with a weight average molecular weight of 30,000 or more, cellulose with a weight average molecular weight of at least 30,000 or more is used. As a result, a self-supporting bioadhesive membrane having a thickness of 6500 nm or less can be produced. 150,
A cellulose solution having a weight average molecular weight of at least 150,000 or more may be used to prepare a regenerated cellulose membrane having a weight average molecular weight of 150,000 or more. In this case, a self-supporting bioadhesive membrane having a thickness of 1300 nm or less can be produced. Thus, by increasing the weight average molecular weight of the cellulose used in the preparation of the cellulose solution, more hydroxyl groups are included in one molecular chain. As a result, many intermolecular hydrogen bonds can be formed, and a thinner membrane to be applied to a living body can be stably produced. The cellulose used for preparing the cellulose solution is not particularly limited as long as it has the desired weight average molecular weight. The cellulose used to prepare the cellulose solution can be, for example, cellulose derived from plants such as pulp and cotton, or cellulose produced by organisms such as bacteria. The impurity concentration in the cellulose raw material is, for example, 10% by weight or less. When the weight average molecular weight of the regenerated cellulose is 2,000,000 or less, it is useful because it becomes 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 less. The ionic liquid contained in the first solvent is, for example, an ionic liquid containing an amino acid or an alkyl phosphate. By containing such an ionic liquid in the first solvent, cellulose can be dissolved while suppressing a decrease in the molecular weight of cellulose. In particular, since amino acids are components that exist in living organisms, ionic liquids containing amino acids are advantageous in forming the bioadhesive membrane 10 that is safer for living organisms.

Cellulose may be dissolved using an ionic liquid that has been pre-diluted with a solvent that does not precipitate cellulose. For example, a mixture of an aprotic polar solvent and an ionic liquid may be used as the first solvent. Aprotic polar solvents are less likely to form hydrogen bonds and are less likely to deposit 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 Formula (II), the anion is an amino acid. In this ionic liquid, the anion contains a terminal carboxyl group and a terminal amino group, as described in formula (II). The cation of the ionic liquid represented by formula (II) may be a quaternary ammonium cation.

In formula (II), R ₁ to R ₆ independently represent a hydrogen atom or a substituent. Substituents can be alkyl groups, hydroxyalkyl groups, or phenyl groups. Substituents may contain branches in the carbon chain. Substituents may contain functional groups such as amino groups, hydroxyl groups, or carboxyl groups. n is 4 or 5, for example.

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.

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

The concentration of cellulose in the cellulose solution is typically 0.2-15% by weight. When the concentration of cellulose in the cellulose solution is 0.2% by weight or more, the thickness of the biological adhesive patch 10 can be reduced and the biological adhesive adhesive 10 having the strength necessary to maintain its shape can be obtained. Moreover, 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 concentration of cellulose in the cellulose solution may be 1-10% 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 with less cellulose precipitation 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 of water on the surface of the substrate is, for example, 70° or less. 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, the cellulose solution can be prevented from entering the interior of the substrate, and the membrane 10 for biological patch can be easily separated from the substrate in a post-process.

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

Methods for forming a liquid film of a cellulose solution on a substrate include, for example, gap coating, slot die coating, spin coating, and coating using a bar coater (metering), in which a predetermined gap is formed between the surface of the substrate and the substrate using an applicator. rod coating) and gravure coating. The thickness of the liquid film adjusted by the thickness of the gap or the size of the opening of the slot die and the coating speed, the rotation speed of the spin coat, the depth of the groove of the bar coater or gravure coat, the coating speed, etc., and the concentration of the cellulose solution. By adjusting the thickness, the thickness of the membrane to be applied to a living body can be adjusted. The method of 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.

At least one of the cellulose solution and the substrate may be heated when forming the liquid film of the cellulose solution on the substrate. This heating may be carried out, for example, in a temperature range (eg, 40-100° C.) capable of keeping the cellulose solution 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 (eg, 50 to 200° C.) lower than the decomposition temperature of the ionic liquid contained in the first solvent. By heating the liquid film at such a temperature, the solvent (for example, the second solvent) other than the ionic liquid can be appropriately removed, and the strength of the biological patch 10 tends to increase. Heating of the liquid film may be performed in a reduced pressure environment. In this case, the solvent other than the ionic liquid can be appropriately removed in a shorter time at a temperature lower than the boiling point of the solvent.

After forming the liquid film of the cellulose solution on the substrate, the liquid film may be gelled. For example, by exposing the liquid film to the vapor of a liquid that is soluble in the ionic liquid and does not dissolve cellulose, the liquid film is gelled and a polymer gel sheet can be obtained. For example, when 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, thereby lowering the solubility of cellulose in the liquid film. As a result, some of the cellulose molecules are precipitated to form a three-dimensional structure. As a result, the liquid film gels. The presence or absence of a gelation point can be determined by whether or not the gelled film can be lifted.

The heating of the liquid film may be performed before gelation of the liquid film, may be performed after gelation of the liquid film, or may be performed before or after gelation 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, some of the components contained in the cellulose solution other than the cellulose and the ionic liquid (for example, the second solvent) may be removed. The rinse liquid is typically a liquid that can be dissolved 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 the adhesive component solution. At this time, the solution of the adhesive component may further contain the active ingredient described above. The solvent in the adhesive component solution is, for example, the 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 adhesive component solution, the adhesive component may be adhered 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-described active ingredient, separately from immersion in the solution of the adhesive component.

Next, unnecessary components such as 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. A method for drying the polymer gel sheet may be vacuum heating. Conditions for drying the polymer gel sheet are not particularly limited. As conditions for drying the polymer gel sheet, a time and temperature sufficient for removing the second solvent and the rinsing liquid are selected. The bioadhesive film 10 is obtained by removing the solvent from the polymer gel sheet.

In the step of drying the polymer gel sheet, for example, when freeze-drying is applied, a solvent that can be frozen and has a boiling point of around 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 dimethylsulfoxide.

In the above method, the polymer gel sheet is immersed in the adhesive component solution prior to drying the polymer gel sheet. good. For example, a polymer sheet obtained by drying a polymer gel sheet may be immersed in a solution of an adhesive component. At this time, the solution of the adhesive component may further contain the active ingredient described above. After that, the immersed polymer sheet is further dried. Also in this case, the adhesive component may be adhered to the polymer gel sheet by spraying, vapor deposition, or coating.

The bioadhesive film of the present disclosure will be described in more detail by way of examples. It should be noted that the bioadhesive film of the present disclosure is not limited to the following examples. First, the evaluation test of the membranes to be applied to a living body according to each example and each comparative example will be described.

<Peeling test>
After dropping a commercially available beauty essence onto the skin on the inner side of the forearm, the bioadhesive film according to each example and each comparative example was attached. After 15 minutes had passed, the biological adhesive film was rubbed with a cotton swab, and the number of times until the biological adhesive film was peeled from the skin was measured.

<Durability test>
After dripping a commercially available beauty essence onto the skin on the inner side of the forearm, the bioadhesive films according to some of the examples and some of the comparative examples were attached. After 6 hours had passed, it was confirmed whether the membrane for biological application was completely peeled off from the skin. The case where the film was not peeled was evaluated as OK, and the case where it was peeled was evaluated as NG.

(Example 1A)
A cellulose solution having a purity of 90% or more and derived from bleached wood pulp was dissolved in an ionic liquid to prepare a cellulose solution. As an ionic liquid, in formula (III),
An ionic liquid in which R ₁ is a methyl group and each of R ₂ , R ₃ and R ₄ is an ethyl group was used. A cellulose solution was applied onto a substrate and the coating film was gelled to form a polymer gel sheet. At this time, the thickness of the coating film of the cellulose solution was adjusted so that the thickness of the biological adhesive film was 2400 nm. After that, the substrate and the polymer gel sheet were washed using a predetermined rinse liquid. Next, the washed polymer gel sheet was immersed in an aqueous solution of sodium polyglutamate having a weight-average molecular weight of 2,000,000, and then the polymer gel sheet was dried to obtain a biological adhesive membrane according to Example 1A. rice field. The biological adhesive film according to Example 1A had a square shape of about 5 cm square in plan view, and had a transparent appearance.

Here, the concentration of sodium polyglutamate contained in the biological adhesive membrane was determined by the method described below. A plurality of sodium polyglutamate aqueous solutions with different concentrations were prepared by dissolving sodium polyglutamate in ultrapure water. The absorbance of the sodium polyglutamate aqueous solution in these aqueous solutions to light with a wavelength of 210 nm was measured with an absorptiometer (manufactured by Shimadzu Corporation, product name: UV-1600). A calibration curve was prepared based on the concentration and absorbance of the sodium polyglutamate aqueous solution, and the slope a ₂₁₀ of the calibration curve was determined. Next, the biological adhesive membrane according to Example 1A is immersed in ultrapure water and subjected to ultrasonic cleaning treatment for 1 hour to extract water-soluble components of the biological adhesive membrane into the ultrapure water, A sample liquid was obtained. The absorbance I ₂₁₀ of the sample solution for light with a wavelength of 210 nm was measured using the absorptiometer described above. From this measurement result, based on the slope a ₂₁₀ , the mass Mp
It was determined. The mass Mp was regarded as the mass of sodium polyglutamate contained in the biological adhesive film according to Example 1A. As a result, the mass of sodium polyglutamate contained in the biological adhesive film according to Example 1A was 0.05% with respect to the mass of the biological adhesive film according to Example 1A.

(Example 1B)
Example 1A was performed in the same manner as in Example 1A, except that the immersion conditions were changed so that the mass of sodium polyglutamate contained in the biological patch film was 0.2% with respect to the mass of the biological patch film. A film to be applied to a living body according to 1B was produced.

(Example 1C)
Example 1A was performed in the same manner as in Example 1A, except that the immersion conditions were changed so that the mass of sodium polyglutamate contained in the biological patch film was 1.2% with respect to the mass of the biological patch film. A film to be applied to a living body according to 1C was produced.

(Example 1D)
Example 1A was performed in the same manner as in Example 1A, except that the immersion conditions were changed so that the mass of sodium polyglutamate contained in the biological patch film was 2.3% with respect to the mass of the biological patch film. A film to be applied to a living body according to 1D was produced.

(Example 1E)
In the same manner as in Example 1A, except that the immersion conditions were changed so that the mass of sodium polyglutamate contained in the biological patch film was 7.1% with respect to the mass of the biological patch film. A film to be applied to a living body according to 1E was produced.

(Example 1F)
Example 1A was performed in the same manner as in Example 1A, except that the immersion conditions were changed so that the mass of sodium polyglutamate contained in the biological patch film was 12.4% with respect to the mass of the biological patch film. A film to be applied to a living body according to 1F was produced.

(Example 1G)
In the same manner as in Example 1A, except that the immersion conditions were changed so that the mass of sodium polyglutamate contained in the biological patch film was 24.8% with respect to the mass of the biological patch film. A film to be applied to a living body according to 1G was produced.

(Comparative Example 1A)
A biological adhesive membrane according to Comparative Example 1A was produced in the same manner as in Example 1A, except that the immersion of the polymer gel sheet in the aqueous solution of sodium polyglutamate was omitted.

Table 1 shows the results of the peel test of the bioadhesive films according to Examples 1A to 1G and Comparative Example 1A. In addition, "-" in Table 1 means that the durability test was not performed. In addition, results of endurance tests of the membranes to be applied to living bodies according to Examples 1A, 1D, and 1G are shown. After being attached to the skin, the membranes to be applied to a living body according to Examples 1A to 1G were easily peeled off from the skin with running water, leaving no trace of attachment on the skin.

As shown in Table 1, a comparison between Examples 1A to 1G and Comparative Example 1A shows that the number of times until peeling from the living body in the peeling test increases when the film for biological patch contains sodium polyglutamate. was done. As the concentration of sodium polyglutamate in the bioadhesive film increased to 12.4% by mass, the number of peeling times from the living body in the peel test increased. In addition, the biological adhesive films according to Examples 1A, 1D, and 1G were still attached to the skin even after 6 hours had passed since they were attached to the skin. It was shown that the membrane to be patched to a living body firmly adheres to the living body by containing sodium polyglutamate.

(Example 2A)
A polymer gel sheet was formed in the same manner as in Example 1A, except that the thickness of the coating film of the cellulose solution was adjusted so that the thickness of the bioadhesive film was 450 nm. Furthermore, in the same manner as in Example 1A, except that the immersion conditions were changed so that the mass of sodium polyglutamate contained in the biological patch film was 2.3% with respect to the mass of the biological patch film, A film to be applied to a living body according to Example 2A was produced.

(Example 2B)
A polymer gel sheet was formed in the same manner as in Example 1A, except that the thickness of the coating film of the cellulose solution was adjusted so that the thickness of the bioadhesive film was 800 nm. Furthermore, in the same manner as in Example 1A, except that the immersion conditions were changed so that the mass of sodium polyglutamate contained in the biological patch film was 2.3% with respect to the mass of the biological patch film, A film to be applied to a living body according to Example 2B was produced.

(Example 2C)
A polymer gel sheet was formed in the same manner as in Example 1A, except that the thickness of the coating film of the cellulose solution was adjusted so that the thickness of the bioadhesive film was 1500 nm. Furthermore, in the same manner as in Example 1A, except that the immersion conditions were changed so that the mass of sodium polyglutamate contained in the biological patch film was 2.3% with respect to the mass of the biological patch film, A film to be applied to a living body according to Example 2C was produced.

(Example 2D)
A polymer gel sheet was formed in the same manner as in Example 1A, except that the thickness of the coating film of the cellulose solution was adjusted so that the thickness of the bioadhesive film was 3700 nm. Furthermore, in the same manner as in Example 1A, except that the immersion conditions were changed so that the mass of sodium polyglutamate contained in the biological patch film was 2.3% with respect to the mass of the biological patch film, A film to be applied to a living body according to Example 2D was produced.

(Example 2E)
A polymer gel sheet was formed in the same manner as in Example 1A, except that the thickness of the coating film of the cellulose solution was adjusted so that the thickness of the bioadhesive film was 5100 nm. Furthermore, in the same manner as in Example 1A, except that the immersion conditions were changed so that the mass of sodium polyglutamate contained in the biological patch film was 2.3% with respect to the mass of the biological patch film, A film to be applied to a living body according to Example 2E was produced.

(Example 2F)
A polymer gel sheet was formed in the same manner as in Example 1A, except that the thickness of the coating film of the cellulose solution was adjusted so that the thickness of the bioadhesive film was 6500 nm. Furthermore, in the same manner as in Example 1A, except that the immersion conditions were changed so that the mass of sodium polyglutamate contained in the biological patch film was 2.3% with respect to the mass of the biological patch film, A film to be applied to a living body according to Example 2F was produced.

(Comparative Example 2A)
A biological adhesive film according to Comparative Example 2A was prepared in the same manner as in Comparative Example 1A, except that the thickness of the coating film of the cellulose solution was adjusted so that the biological adhesive film had a thickness of 1500 nm.

(Comparative Example 2B)
A biological adhesive film according to Comparative Example 2B was produced in the same manner as in Comparative Example 1A, except that the thickness of the coating film of the cellulose solution was adjusted so that the biological adhesive film had a thickness of 5100 nm.

(Comparative Example 2C)
A biological adhesive film according to Comparative Example 2C was produced in the same manner as in Comparative Example 1A, except that the thickness of the coating film of the cellulose solution was adjusted so that the biological adhesive film had a thickness of 6500 nm.

Table 2 shows the results of the peel test of the bioadhesive films according to Examples 1D and 2A to 2F and Comparative Examples 1A and 2A to 2C. "-" in Table 2 means that no adhesive component is supported. After being attached to the skin, the membranes to be applied to a living body according to Examples 2A to 2F were easily peeled off from the skin with running water, leaving no trace of attachment on the skin.

As shown in Table 2, when the thickness of the biological adhesive film is in the range of 450 to 6500 nm, the number of times until the biological adhesive film is peeled from the living body in the peeling test of the biological adhesive film according to the example is less than the biological adhesive film according to the comparative example. It was larger than the number of peeling from the living body in the film peeling test. It was shown that even if the thickness of the bioadhesive film changes in the range of 450 to 6500 nm, the bioadhesive film contains sodium polyglutamate and firmly adheres to the biomedical body. .

(Example 3A)
A membrane to be applied to a living body according to Example 3A was produced in the same manner as in Example 1A, except for the following points. An aqueous solution of sodium polyglutamate with a weight average molecular weight of 15,000 was used instead of an aqueous solution of sodium polyglutamate with a weight average molecular weight of 2,000,000. The conditions for immersion were adjusted so that the mass of sodium polyglutamate contained in the membrane to be patched to a biological body was 12.4% of the mass of the membrane to be patched to a biological body.

(Example 3B)
A membrane to be applied to a living body according to Example 3B was produced in the same manner as in Example 1A, except for the following points. An aqueous solution of sodium polyglutamate with a weight average molecular weight of 400,000 was used instead of an aqueous solution of sodium polyglutamate with a weight average molecular weight of 2,000,000. The conditions for immersion were adjusted so that the mass of sodium polyglutamate contained in the membrane to be patched to a biological body was 12.4% of the mass of the membrane to be patched to a biological body.

(Comparative Example 3A)
A membrane to be applied to a living body according to Comparative Example 3A was produced in the same manner as in Example 1A, except for the following points. An aqueous solution of sodium glutamate was used instead of an aqueous solution of sodium polyglutamate having a weight average molecular weight of 2,000,000. The immersion conditions were adjusted so that the mass of sodium glutamate contained in the membrane to be patched to a biological body was 12.4% of the mass of the membrane to be patched to a biological body. The mass of sodium glutamate contained in the biological patch was determined according to the method described in Example 1A.

Table 3 shows the results of the peel test of the membranes for bioadhesion according to Examples 1D, 3A and 3B and Comparative Examples 1A and 3A. After being attached to the skin, the bioadhesive membranes according to Examples 3A and 3B were easily peeled off from the skin with running water, leaving no trace of attachment on the skin.

As shown in Table 3, the number of times until peeling from the living body in the peeling test of the film to be applied to a living body containing 12.4% by mass of sodium polyglutamate having a weight average molecular weight of 15,000 or more was lower than that of Comparative Examples 1A and 3A. It was more than that of the membrane for application to a living body. Therefore, it was shown that if the film to be patched to a living body contains sodium polyglutamate, the film to be patched to a living body firmly adheres to the body even if the weight average molecular weight of the sodium polyglutamate changes.

(Example 4A)
A membrane to be applied to a living body according to Example 4A was produced in the same manner as in Example 1A, except for the following points. An aqueous solution of polytyrosine with a weight average molecular weight of 20,000 was used instead of an aqueous solution of sodium polyglutamate with a weight average molecular weight of 2,000,000. The conditions for immersion were adjusted so that the mass of polytyrosine contained in the membrane to be patched to a living body was 12.4% with respect to the mass of the membrane to be patched to a living body. The mass of polytyrosine contained in the biological patch was determined according to the method described in Example 1A.

(Example 4B)
A membrane to be applied to a living body according to Example 4B was produced in the same manner as in Example 1A, except for the following points. An aqueous solution of polylysine hydrochloride with a weight average molecular weight of 25,000 was used instead of an aqueous solution of sodium polyglutamate with a weight average molecular weight of 2,000,000. The immersion conditions were adjusted so that the mass of polylysine hydrochloride contained in the membrane to be patched to a living body was 12.4% with respect to the mass of the membrane to be patched to a living body. The mass of polylysine hydrochloride contained in the biological patch was determined according to the method described in Example 1A.

(Example 4C)
A membrane to be applied to a living body according to Example 4C was produced in the same manner as in Example 1A, except for the following points. An aqueous solution of polyarginine with a weight average molecular weight of 10,000 was used instead of an aqueous solution of sodium polyglutamate with a weight average molecular weight of 2,000,000. The immersion conditions were adjusted so that the mass of polyarginine contained in the membrane to be patched to a living body was 12.4% with respect to the mass of the membrane to be patched to a living body. The mass of polyarginine contained in the biological adhesive film was determined according to the method described in Example 1A.

(Example 4D)
A membrane to be applied to a living body according to Example 4D was produced in the same manner as in Example 1A, except for the following points. An aqueous solution of polyornithine hydrochloride with a weight average molecular weight of 22,500 was used instead of an aqueous solution of sodium polyglutamate with a weight average molecular weight of 2,000,000. The immersion conditions were adjusted so that the mass of polyornithine hydrochloride contained in the membrane to be patched to a living body was 12.4% of the mass of the membrane to be patched to a living body. The mass of polyornithine hydrochloride contained in the biological adhesive film was determined according to the method described in Example 1A.

(Example 4E)
A membrane for application to a living body according to Example 4E was produced in the same manner as in Example 1A, except for the following points. Instead of an aqueous solution of sodium polyglutamate with a weight average molecular weight of 2,000,000, an aqueous solution of sodium polyaspartate with a weight average molecular weight of 15,000 was used. The immersion conditions were adjusted so that the mass of sodium polyaspartate contained in the membrane to be patched to a biological body was 12.4% of the mass of the membrane to be patched to a biological body. The mass of sodium polyaspartate contained in the biological adhesive film was determined according to the method described in Example 1A.

(Example 4F)
A membrane for application to a living body according to Example 4F was produced in the same manner as in Example 1A, except for the following points. An aqueous solution of polyhistidine with a weight average molecular weight of 15,000 was used instead of an aqueous solution of sodium polyglutamate with a weight average molecular weight of 2,000,000. The conditions for immersion were adjusted so that the mass of polyhistidine contained in the membrane to be patched to a living body was 12.4% with respect to the mass of the membrane to be patched to a living body. The mass of polyhistidine contained in the bioadhesive film is
Determined according to the method described in Example 1A.

Table 4 shows the results of the peel test of the bioadhesive films according to Examples 3A, 4A to 4F and Comparative Example 1A. After being attached to the skin, the membranes to be applied to a living body according to Examples 4A to 4F were easily peeled off from the skin with running water, leaving no trace of attachment on the skin.

As shown in Table 4, when a polyamino acid having a weight-average molecular weight of 10,000 or more was included in the membrane for adhesive application to a living body at a concentration of 12.4%, the number of peeling times from the living body in the peeling test was large. Therefore, even if the type of polyamino acid contained in the film to be patched to a living body changes, the film to be patched to a biological body was shown to firmly adhere to the living body.

(Example 5A)
A polymer gel sheet was formed in the same manner as in Example 1A, except that the thickness of the coating film of the cellulose solution was adjusted so that the thickness of the bioadhesive film was 800 nm. This polymer gel sheet was dried without being immersed in an aqueous solution of sodium polyglutamate to obtain a polymer sheet. This polymer sheet was immersed in an aqueous solution of sodium polyglutamate having a weight-average molecular weight of 2,000,000, and then the polymer sheet was dried to prepare a biological patch film according to Example 5A. The conditions for immersion were adjusted so that the mass of sodium polyglutamate contained in the membrane to be patched to a living body was 2.4% with respect to the mass of the membrane to be patched to a living body.

(Comparative Example 5A)
Polylactic acid having a weight average molecular weight of 250,000 was dissolved in chloroform to prepare a chloroform solution of polylactic acid (concentration of polylactic acid: 2.4% by mass). A chloroform solution of polylactic acid was applied by spin coating onto a substrate having a surface formed of polyvinyl alcohol having a weight average molecular weight of about 500 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 bioadhesive membrane according to Comparative Example 5A made of polylactic acid.

(Comparative Example 5B)
A polylactic acid film prepared in the same manner as in Comparative Example 5A was immersed in an aqueous solution of sodium polyglutamate having a weight-average molecular weight of 2,000,000. A sticking film was produced. The conditions for immersion were adjusted so that the mass of sodium polyglutamate contained in the membrane to be patched to a living body was 2.4% with respect to the mass of the membrane to be patched to a living body.

Table 5 shows the results of the peel test and durability test of the membranes to be applied to a living body according to Example 5A, Comparative Example 5A, and Comparative Example 5B. In addition, after the membrane for bioadhesion according to Example 5A was applied to the skin, it was easily peeled off from the skin with running water, leaving no trace of attachment on the skin.

As shown in Table 5, the film for bioadhesive application of Example 5A containing sodium polyglutamate and regenerated cellulose exhibited a large number of times until it was peeled off from the living body in the peel test. In addition, the membrane for bioadhesion of Example 5A was still adhered to the skin even after 6 hours had passed since it was applied to the skin. Therefore, it was shown that the bioadhesive film containing sodium polyglutamate and regenerated cellulose firmly adheres to the living body.

REFERENCE SIGNS LIST 10 Film for sticking to a living body 11 First main surface 12 Second main surface 13 Regenerated cellulose 14 Adhesive component 21 First protective layer 22 Second protective layer 50a, 50b Laminate

Claims (11)

Containing regenerated cellulose and an adhesive component attached to the regenerated cellulose,
is self-supporting with a thickness of 20 to 6500 nm,
The adhesive component contains a polyamino acid,
A film to be attached to a living body. The biological patch according to claim 1, wherein the regenerated cellulose has a weight average molecular weight of 30,000 or more. 3. The polyamino acid according to claim 1 or 2, wherein the repeating structural unit has at least one functional group selected from the group consisting of a hydroxyl group, an aldehyde group, a carboxyl group, an amino group, a guanidino group, and a carbonyl group. A film to be attached to a living body. The adhesive component contains one or more polyamino acids selected from the group consisting of polyglutamic acid, polytyrosine, polylysine, polyarginine, polyornithine, polyaspartic acid, polyhistidine, and salts thereof. Item 4. The membrane for biological patch according to any one of Items 1 to 3. The biological adhesive membrane according to any one of claims 1 to 4, wherein at least part of the adhesive component is present on the surface of the biological adhesive membrane. The biological patch according to any one of claims 1 to 5, wherein at least part of the adhesive component is continuously present between the surface of the biological adhesive film and the regenerated cellulose in the thickness direction. membrane. The biological adhesive film according to any one of claims 1 to 6, wherein the adhesive component content in the biological adhesive film is 0.05 to 50% by weight. The biological patch according to any one of claims 1 to 7, wherein the polyamino acid has a weight average molecular weight of 10,000 or more. The film for biological application according to any one of claims 1 to 8;
a first protective layer disposed on the first main surface of the biological adhesive membrane and removable from the first main surface;
laminate. 10. The laminate according to claim 9, further comprising a second protective layer disposed on a second main surface of the membrane for application to a living body, which is located on the opposite side of the first main surface. A cosmetic method for attaching a film to be attached to a living body, comprising:
The bioadhesive membrane comprises regenerated cellulose and an adhesive component containing a polyamino acid attached to the regenerated cellulose, and is self-supporting and has a thickness of 20 to 6500 nm,
attaching a water-containing adhesive to a biological tissue and the biological adhesive film, and attaching the biological adhesive film to the biological tissue;
beauty method.

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