阅读说明：本技术 生物体贴附用膜、叠层体及美容方法
(Film for biological adhesion, laminate, and cosmetic method
) 是由 青木贵裕
川岛知子
谷池优子 于 2019-02-07 设计创作，主要内容包括：本公开提供包含再生纤维素,并且对生物体组织具有高密合性的生物体贴附用膜。本公开的生物体贴附用膜(10)包含再生纤维素、和粘接成分。粘接成分附着于再生纤维素。生物体贴附用膜(10)为具有20～6500nm的厚度的自支持型。粘接成分含有聚氨基酸。生物体贴附用膜(10)没有支持体也可以维持膜的形态。(Disclosed is a film for biological adhesion, which contains regenerated cellulose and has high adhesion to biological tissues. The disclosed film (10) for biological adhesion contains regenerated cellulose and an adhesive component. The binding component adheres to the regenerated cellulose. The film (10) for biological adhesion is a self-supporting film having a thickness of 20 to 6500 nm. The adhesive component contains polyamino acid. The biological adhesion membrane (10) can maintain the form of the membrane without a support.)
1. A film for biological adhesion, which comprises regenerated cellulose and an adhesive component adhering to the regenerated cellulose,
the film for organism adhesion is a self-supporting type having a thickness of 20 to 6500nm,
the adhesive component contains a polyamino acid.
2. The film for biological application according to claim 1, wherein the regenerated cellulose has a weight average molecular weight of 30,000 or more.
3. The film for biological attachment according to claim 1 or 2, wherein the polyamino acid has at least 1 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.
4. The film for biological attachment according to any one of claims 1 to 3, wherein the adhesive component contains 1 or more kinds of polyamino acids selected from the group consisting of polyglutamic acid, polytyrosine, polylysine, polyarginine, polyornithine, polyaspartic acid, polyhistidine, and salts thereof.
5. The film for biological adhesion according to any one of claims 1 to 4, wherein at least a part of the adhesive component is present on a surface of the film for biological adhesion.
6. The film for biological adhesion according to any one of claims 1 to 5, wherein at least a part of the adhesive component is continuously present between the regenerated celluloses in a thickness direction from a surface of the film for biological adhesion.
7. The film for biological application according to any one of claims 1 to 6, wherein the content of the adhesive component in the film for biological application is 0.05 to 50% by weight.
8. The film for biological attachment according to any one of claims 1 to 7, wherein the polyamino acid has a weight average molecular weight of 10,000 or more.
9. A laminate comprising:
the film for biological application according to any one of claims 1 to 8; and
a first protective layer that is disposed on a first main surface of the biological adhesion film and is removable from the first main surface.
10. The laminate according to claim 9, further comprising a second protective layer disposed on a second main surface of the biological adhesion film opposite to the first main surface.
11. A cosmetic method for attaching a film for organism adhesion,
the film for biological adhesion comprises regenerated cellulose and an adhesive component containing polyamino acid and attached to the regenerated cellulose, and is a self-supporting film having a thickness of 20 to 6500nm,
in the cosmetic method, a wearing agent containing water is attached to a living tissue and the biological adhesion film, and the biological adhesion film is adhered to the living tissue.
Technical Field
The present disclosure relates to a film for biological adhesion, a laminate, and a cosmetic method.
Background
Conventionally, a biological adhesive film to be adhered to a living tissue such as skin is known.
For example, patent document 1 describes a cosmetic method having an excellent effect of preventing a cosmetic material such as foundation containing a large amount of a coloring material such as a pigment from adhering to clothes, i.e., a cosmetic material having a small secondary adhesion, and also describes a film used in the cosmetic method. The film is composed of a base material film and a support, wherein the base material film has a thickness of 10-500 nm. In the cosmetic method described in patent document 1, a base film is attached to the skin, and the support of the attached film is removed. The material of the substrate film is polylactic acid and other materials. The substrate film carries components such as hyaluronic acid.
Patent document 2 describes a self-retaining cosmetic sheet to be applied to the skin for a predetermined cosmetic method. The self-sustaining cosmetic sheet comprises at least 1 biocompatible and/or biodegradable hydrophobic polymer layer. Examples of the biocompatible and/or biodegradable polymer include non-crosslinked polymers such as non-crosslinked polylactic acid. The hydrophobic polymer layer comprises, for example, at least 1 cationic polymer and at least 1 anionic polymer.
Disclosure of Invention
Problems to be solved by the invention
In the techniques described in patent documents 1 and 2, the adhesion of a film for biological adhesion containing regenerated cellulose to a biological tissue was not examined at all. Accordingly, the present disclosure provides a film for biological adhesion, which contains regenerated cellulose and has high adhesion to a biological tissue.
Means for solving the problems
Disclosed is a film for biological adhesion, which comprises regenerated cellulose and an adhesive component that adheres to the regenerated cellulose,
the film for biological adhesion is a self-supporting film having a thickness of 20 to 6500nm,
the adhesive component contains a polyamino acid.
Additional effects and advantages of the disclosed embodiments will be apparent from the description and drawings. Effects and/or advantages are provided by various embodiments or features disclosed in the specification and the drawings, respectively, not all of which are required in order to obtain 1 or more of them.
ADVANTAGEOUS EFFECTS OF INVENTION
The above-mentioned membrane for biological adhesion contains regenerated cellulose and has high adhesion to a biological tissue.
Drawings
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 regenerated cellulose and an adhesive component in the biological patch film of the present disclosure.
Fig. 2A is a diagram showing a method of using the biological adhesion film of the present disclosure.
Fig. 2B is a diagram showing a method of using the biological patch film of the present disclosure.
Fig. 2C is a diagram showing a method of using the biological adhesion film of the present disclosure.
Fig. 3 is a sectional view schematically showing another example of the laminate of the present disclosure.
Detailed Description
(knowledge forming the basis of the present disclosure)
The present inventors have developed a self-supporting biological adhesive film having a thickness of several μm or less, which is made of regenerated cellulose and has not been realized in the past. The present inventors have further studied the film for biological adhesion, and as a result, have found that there is room for improvement from the viewpoint of adhesiveness to a biological tissue. Therefore, the present inventors have repeatedly conducted a large number of tests in order to improve the adhesion of the biological adhesion membrane to the biological tissue. As a result, it has newly been found that adhesion of the biological adhesion film to the biological tissue is improved by attaching a predetermined adhesive component to regenerated cellulose in the biological adhesion film. The present inventors have devised a biological adhesive film according to the present disclosure based on this new knowledge.
The outline of the scheme according to the present disclosure is as follows.
(item 1)
A film for biological adhesion, which comprises regenerated cellulose and an adhesive component adhering to the regenerated cellulose,
the film for biological adhesion is a self-supporting film having a thickness of 20 to 6500nm,
the adhesive component contains a polyamino acid.
(item 2)
The film for biological adhesion according to item 1, wherein the regenerated cellulose has a weight average molecular weight of 30,000 or more.
(item 3)
The film for biological attachment according to item 1 or 2, wherein the polyamino acid has at least 1 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.
(item 4)
The membrane for biological attachment according to any one of items 1 to 3, wherein the adhesive component contains 1 or more kinds of polyamino acids selected from the group consisting of polyglutamic acid, polytyrosine, polylysine, polyarginine, polyornithine, polyaspartic acid, polyhistidine, and salts thereof.
(item 5)
The film for biological adhesion according to any one of items 1 to 4, wherein at least a part of the adhesive component is present on a surface of the film for biological adhesion.
(item 6)
The film for biological adhesion according to any one of items 1 to 5, wherein at least a part of the adhesive component is continuously present between the regenerated celluloses in a thickness direction from a surface of the film for biological adhesion.
(item 7)
The film for biological application according to any one of items 1 to 6, wherein the content of the adhesive component in the film for biological application is 0.05 to 50% by weight.
(item 8)
The film for biological attachment 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 laminate comprising:
the film for biological adhesion according to any one of items 1 to 8; and
and a first protective layer that is disposed on the first main surface of the biological adhesion film and is removable from the first main surface.
(item 10)
The laminate according to item 9, further comprising a second protective layer disposed on a second main surface of the biological adhesion film opposite to the first main surface.
(item 11)
A cosmetic method for attaching a film for organism adhesion,
the film for biological adhesion comprises regenerated cellulose and an adhesive component containing polyamino acid and attached to the regenerated cellulose, and is a self-supporting film having a thickness of 20 to 6500nm,
in the cosmetic method, a wearing agent containing water is attached to a living tissue and the biological adhesion film, and the biological adhesion film is adhered to the living tissue.
(embodiment mode)
Hereinafter, embodiments of the present disclosure will be described with reference to the drawings. The following embodiments are merely examples, and the biological adhesion film of the present disclosure is not limited to the following embodiments. The numerical values, shapes, materials, constituent elements, arrangement and connection forms of constituent elements, and steps and order of steps shown in the following embodiments are examples, and are not intended to limit the present disclosure. The following embodiments can be combined with each other as long as no contradiction occurs. Among the components in the following embodiments, components that are not recited in the independent claims indicating the uppermost concept should not be construed as essential components. In the following description, components having substantially the same function are denoted by common reference numerals, and description thereof may be omitted. In order to avoid the drawings from becoming excessively complicated, some elements may not be illustrated.
The biological patch film 10 shown in fig. 1A contains regenerated cellulose and an adhesive component. The binding component adheres to the regenerated cellulose. The regenerated cellulose typically forms a skeleton (base material) of the biological patch film 10. The biological adhesion film 10 is a self-supporting film having a thickness of 20 to 6500 nm. In the present specification, the term "self-supporting membrane" refers to a membrane that can maintain the form of the membrane without a support. For example, when the self-supporting film is picked up by holding a part of the self-supporting film with a finger or tweezers, the self-supporting film can be picked up entirely without a support without breaking the self-supporting film. The adhesive component contains polyamino acid.
Regenerated cellulose is rich in hydroxyl groups in its repeating structure. Therefore, it is considered that the polyamino acid contained in the binder component and the regenerated cellulose interact with each other so as to be pulled by hydrogen bonds. Therefore, in the biological patch film 10, the adhesive component is appropriately attached to the cellulose. It is considered difficult to use polyamino acid as the adhesive component for the base film made of polylactic acid described in patent document 1. This is because there is no functional group capable of forming a hydrogen bond in the repeating structure of polylactic acid, and polylactic acid exhibits hydrophobicity. It is considered that the hydrophilic polyamino acid and the hydrophobic polylactic acid hardly interact with each other, and the polyamino acid is not suitable as an adhesive component in a base film of the polylactic acid.
The outermost surface of living tissues such as skin is mainly composed of proteins such as keratin. Proteins are composed of amide bonds. Therefore, when the biological adhesion membrane 10 is adhered to a living tissue, hydrogen bonds are formed between the amide bonds of the polyamino acid and the amide bonds of the protein, and the biological adhesion membrane 10 can exhibit high adhesion to the living tissue.
The adhesive component contains polyamino acid and has biocompatibility. Biocompatibility is a property of not easily causing a phenomenon harmful to living bodies such as stuffiness and rash when contacting living tissues.
Polyamino acids are, for example, homopolymers of amino acids. In this case, in the polyamino acid, the intramolecular interaction is likely to be reduced due to the influence of electric charge, hydrophilicity, hydrophobicity, or the like. Therefore, among polyamino acids, folding is less likely to occur and a uniform structure is easily formed, as compared with proteins or peptides in which various amino acids are arranged. Thus, the polyamino acid is likely to have a site capable of interaction at the outside, and is likely to interact with a living tissue or regenerated cellulose. As a result, the adhesiveness of the biological adhesion film 10 to the biological tissue is more reliably improved.
Polyamino acids are typically water soluble. In this case, the biological adhesion film 10 can be easily peeled off from the living tissue using an aqueous solution or the like, and the biological adhesion film 10 is less likely to remain in the living body. Even if the biological adhesion film 10 remains in the living body, the biological adhesion film 10 is biocompatible and therefore is less likely to cause problems in the living body.
The amino acids forming the polyamino acid may be in the L, D or racemic forms. The amino acids forming the polyamino acid are desirably in the L form. The L-form of amino acids is mainly present in organisms. Therefore, even when the polyamino acid is transdermally absorbed and decomposed into a compound such as an amino acid for some reason, the biological adhesive film 10 is safer if the polyamino acid contained in the adhesive component is L-shaped.
The polyamino acid has, for example, at least 1 functional group selected from the group consisting of a hydroxyl group, an aldehyde group, a carboxyl group, an amino group, a guanidine group, and a carbonyl group in the repeating structural unit. In this case, a large number of hydrogen bonds are formed between the protein such as keratin or regenerated cellulose of the living tissue and the polyamino acid by these functional groups, and the adhesion of the biological adhesion membrane 10 to the living tissue is improved.
The adhesive component contains, for example, at least 1 or more kinds of polyamino acids selected from the group consisting of polyglutamic acid, polytyrosine, polylysine, polyarginine, polyornithine, polyaspartic acid, polyhistidine, polyserine, polyhydroxyproline, polyhydroxylysine, polyglycine, polyalanine, polycysteine, polyiisoleucine, polyleucine, polymeine, polyphenylalanine, polyproline, polytryptophan, polyvaline, polymethine, polyphosphoserine, poly-beta-alanine, poly-gamma-aminobutyric acid, polycreatine, polycitrulline, and salts thereof.
The adhesive component desirably contains at least 1 or more polyamino acids selected from the group consisting of polyglutamic acid, polytyrosine, polylysine, polyarginine, polyornithine, polyaspartic acid, polyhistidine, and salts thereof.
In the biological adhesion film 10 of the present disclosure, the expression "adhesion component adheres to regenerated cellulose" typically means a state in which at least a part of the adhesion component is present on the surface of the biological adhesion film 10. However, the state where the adhesive component is present in contact with the surface of the biological adhesive film 10 is also included in the range of "the adhesive component adheres to the regenerated cellulose". The state in which the adhesive component can be eluted from the surface by wearing the biological adhesion film 10 or the like is also included in the range of "the adhesive component adheres to the regenerated cellulose". For example, a part of the adhesive component in the biological adhesion film 10 is present on the surface of the biological adhesion film 10. Therefore, the adhesive component easily interacts with both regenerated cellulose and the living tissue, and the adhesion of the living tissue adhesion film 10 to the living tissue is further improved. In the thickness direction of the biological adhesive film 10, at least a part of the adhesive component is desirably present continuously between the regenerated celluloses from the surface of the biological adhesive film 10. In this case, the polyamino acid of the adhesive component may form a hydrogen bond with the regenerated cellulose at a position away from the surface of the biological adhesive film 10, and thus is useful.
The adhesive component in the biological adhesive film 10 can be uniformly distributed in the thickness direction of the biological adhesive film 10. The adhesive component may be concentrated at a specific position in the biological adhesive film 10. For example, in the biological adhesion film 10, a plurality of regions in which the adhesive component is present at a high concentration may be present at predetermined intervals. The adhesive component may be present in a layer on the surface of the biological adhesive film 10. In this case, the layer of the adhesive component may cover the entire base material made of regenerated cellulose or may cover a part of the base material.
Fig. 1B shows an example of the positional relationship between the regenerated cellulose 13 and the adhesive component 14 in the biological adhesion film 10. As shown in fig. 1B, in the biological adhesion film 10, a part of the adhesive component 14 is present on the surface of the biological adhesion film 10. In this case, the adhesive component 14 may be in contact with the surface of the regenerated cellulose 13. It is desirable that a part of the adhesive component 14 continuously exist from the inside of the regenerated cellulose 13 to the surface of the biological adhesion film 10 in the thickness direction of the biological adhesion film 10. The physical shape of the adhesive component 14 in the biological adhesion film 10 is not limited to a specific three-dimensional shape. The shape is preferably such that the contact area between the regenerated cellulose 13 and the adhesive component 14 is as large as possible. This improves the adhesion effect of the adhesive composition 14. The adhesive component 14 may be present continuously from one surface (main surface) to the other surface (main surface) of the biological adhesive film 10. A part of the adhesive component 14 may be present only inside the regenerated cellulose 13 without being present on the surface of the biological patch film 10. 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 wt%. In this case, the biological adhesion film 10 can more reliably exhibit high adhesion to the biological tissue. If the content of the adhesive component in the biological adhesive film 10 is 50 wt% or less, the stickiness of the biological adhesive film 10 is suppressed, and the biological adhesive film 10 is easily attached to a living body.
The ratio of the mass of the binder component to the mass of the regenerated cellulose is, for example, 0.05 to 90%, and may be 0.05 to 50%.
The polyamino acid of the binding component has, for example, a weight average molecular weight of 10,000 or more. In this case, the viscosity of the polyamino acid is increased, and the adhesion of the biological adhesion membrane 10 to the biological tissue is more reliably improved. The polyamino acid has a weight average molecular weight of, for example, 10,000 to 10,000,000. The polyamino acid may have a weight average molecular weight of 10,000 to 2,000,000. If the polyamino acid has a weight average molecular weight of 2,000,000 or less, the binding component can be easily attached to the regenerated cellulose. The weight average molecular weight of the polyamino acid can be determined, for example, by Gel Permeation Chromatography (GPC). The sample for GPC measurement can be prepared by, for example, dissolving a commercially available reagent or the like, extracting a commercially available cosmetic material or drug, or extracting a polyamino acid as an adhesive component from the bioadhesive film 10. For example, when the adhesive component is extracted from the biological adhesion film 10, only the polyamino acid can be extracted into the solution by immersing the biological adhesion film 10 in a solution described below and performing a process such as stirring, shaking, ultrasonic processing, or heating. The solution is, for example, water, such as water, methanol, ethanol, or acetic acid, or a highly water-soluble solvent.
Hydrogen bonds are likely to be formed in and/or between molecules in the regenerated cellulose, and the biological adhesion membrane 10 is likely to have a dense structure. The film derived from regenerated cellulose is easy to maintain the shape compared with the film derived from nanofibers of natural cellulose. Further, since cellulose exhibits amphiphilicity, a hydrophilic active ingredient and a hydrophobic active ingredient can be appropriately supported, and the biological adhesion membrane 10 has high versatility.
The raw material of the regenerated cellulose is not particularly limited. For example, the raw material of the regenerated cellulose may be processed cellulose such as natural cellulose derived from plants, natural cellulose derived from organisms, regenerated cellulose such as cellophane, or cellulose nanofibers. The concentration of impurities in the regenerated cellulose raw material is advantageously 10% by weight or less.
The regenerated cellulose is, for example, cellulose substantially represented by the following formula (I). The term "cellulose substantially represented by the formula (I)" means cellulose in which at least 90% of hydroxyl groups of glucose residues in the cellulose represented by the formula (I) remain. The ratio of the number of hydroxyl groups of the glucose residue in the cellulose contained in the biological adhesion film 10 to the number of hydroxyl groups of the glucose residue in the cellulose represented by formula (I) can be quantified by a known method such as X-ray photoelectron spectroscopy (XPS). The regenerated cellulose contained in the biological patch film 10 may have a branched structure in some cases. Artificially derivatized cellulose typically does not correspond to "cellulose substantially represented by formula (I)". On the other hand, the "cellulose substantially represented by the formula (I)" does not exclude the regenerated cellulose by derivatization. Even cellulose regenerated by derivatization may correspond to "cellulose substantially represented by formula (I)".
In the embodiment of the present disclosure, the biological adhesion film 10 is made of regenerated cellulose. The strength of a film formed from a suspension obtained by dispersing natural cellulose fibers in water or the like is borne by hydrogen bonds between nanofibers constituting the cellulose fibers. Therefore, only brittle cellulose films can be obtained. In contrast, in the case of a film made of regenerated cellulose, since the nanofibers are disentangled up to the molecular chain, the strength of the film made of regenerated cellulose is borne by the hydrogen bonds between the cellulose molecular chains. That is, hydrogen bonds between units smaller than nanofibers are uniformly formed in the film made of regenerated cellulose. Therefore, a cellulose film which is less brittle and has appropriate flexibility and is less likely to break can be provided as compared with a case where a film is formed from a suspension obtained by dispersing natural cellulose fibers in water or the like. Here, the "nanofiber" is also referred to as "nanofibril (or microfibril)", which is the most basic unit of cellulose molecules assembled together, has a width of about 4nm to about 100nm, and has a length of, for example, about 1 μm or more.
In the present specification, "regenerated cellulose" refers to cellulose that does not have the crystal structure I peculiar to natural cellulose. The crystal structure of cellulose can be confirmed by XRD patterns. In the XRD pattern using CuK α rays, natural cellulose shows peaks near 14 to 17 ° and 23 ° peculiar to the crystal structure I, but regenerated cellulose tends to have a crystal structure II, peaks near 12 °, 20 ° and 22 °, and no peaks near 14 to 17 ° and 23 °.
For example, 90% or more by mass of the regenerated cellulose included in the biological patch film 10 is regenerated cellulose that has not been chemically modified or derivatized. It is desirable that the regenerated cellulose contained in the biological patch film 10 be 98% by mass or more of regenerated cellulose that has not been chemically modified or derivatized. In this case, it is considered that cellulose which has not been chemically modified or derivatized is contained in a large amount in the biological patch film 10, and that cellulose contains more hydroxyl groups per 1 molecular chain. Therefore, it is considered that more hydrogen bonds are formed between the molecules of cellulose, and the biological adhesion membrane 10 tends to have high strength. The regenerated cellulose contained in the biological patch film 10 may be uncrosslinked.
The cellulose contained in the biological patch film 10 has, for example, 0 to 12% crystallinity. In this case, the amount of hydroxyl groups involved in the formation of the crystal structure is appropriately small, and the adhesion of the biological adhesive film 10 to the living body tends to be high. The biological adhesion membrane 10 can exhibit various functions by performing a predetermined chemical modification at a site where a hydroxyl group should be present.
The crystallinity of the Cellulose contained in the membrane for biological application 10 can be measured, for example, by using the Cellulose as reported in Park et al, "Cellulose crystallization index and Cellulose esterification performance" Biotechnology for Biofuels 2010,31013C-NMR method. According to the method, the solid is passed through13A peak in the vicinity of 87 to 93ppm in a spectrum obtained by C-NMR measurement is considered to be derived from a crystal structure, a broad peak in the vicinity of 80 to 87ppm is considered to be derived from an amorphous structure, and when the former peak area is represented by X and the latter peak area is represented by Y, the crystallinity is determined by the following formula. In the following formula, "×" represents a multiplication operation.
(crystallinity)% (X/(X + Y)) × 100
As described above, the biological adhesion film 10 has a thickness of 20 to 6500 nm. If the thickness of the biological adhesion film 10 is 20nm or more, the biological adhesion film 10 can function as a self-supporting film that can be adhered to a biological tissue. If the thickness of the biological adhesion film 10 is 6500nm or less, the biological adhesion film 10 is less likely to be peeled off by friction, stress from the skin, or the like when the biological adhesion film 10 is adhered to a biological tissue. On the other hand, the biological adhesion film 10 can be easily peeled off from the biological tissue using an aqueous solution or the like. The thickness of the biological adhesion film 10 is determined by, for example, measuring the thicknesses of the biological adhesion film 10 at a plurality of positions and averaging the thicknesses. The thickness at each position can be measured, for example, using a stylus profilometer system DEKTAK (registered trademark) made of ブルカーナノインコーポレイテッド.
The thickness of the biological adhesion film 10 may be 100nm or more. If the thickness of the biological adhesion film 10 is 100nm or more, the strength of the biological adhesion film 10 is improved, and the biological adhesion film 10 can be handled easily. The thickness of the biological adhesion film 10 may be 300nm or more. When the thickness of the biological adhesion film 10 is 300nm or more, the strength of the biological adhesion film 10 is further improved, and the biological adhesion film 10 is not easily broken and can be easily used. The thickness of the biological adhesion film 10 may be 500nm or more. When the thickness of the biological adhesion film 10 is 500nm or more, more effective components such as cosmetic components can be retained in the biological adhesion film 10. The thickness of the biological adhesion film 10 may be 2000nm or less. If the thickness of the biological adhesion film 10 is 2000nm or less, the biological adhesion film 10 has high adhesion to a biological tissue, and the biological adhesion film 10 can be stably adhered to the surface of a biological tissue such as skin. The thickness of the biological adhesive film 10 may be 1300nm or less. When the thickness of the biological adhesion film 10 is 1300nm or less, the adhesion of the biological adhesion film 10 to the biological tissue becomes higher, and the state in which the biological adhesion film 10 is stably adhered to the surface of the biological tissue such as the skin for a long time can be maintained.
The shape of the biological adhesion film 10 in a plan view of the biological adhesion film 10 is not particularly limited. The biological adhesion film 10 may have a circular shape, an elliptical shape, or a polygonal shape in a plan view. The biological adhesion film 10 may be amorphous in a plan view.
The biological adhesion film 10 may be a single-layer film or a film having a laminated structure in which a plurality of layers are laminated. When the biological adhesion film 10 has a laminated structure, the active ingredients held by the plurality of layers may be the same or different for each layer. The biological patch film 10 may have a laminated structure including a layer containing cellulose and a laminated layer made of a material other than cellulose.
In the case of cosmetic use, the film 10 for biological application is used for, for example, (i) skin care such as whitening, moisturizing, and anti-wrinkle, (ii) hair care such as hair growth, depilation, and hair styling, or (iii) color cosmetics such as foundation, face powder, and nail. In the case of medical use, the biological patch film 10 is used for administration to a living body of a drug such as an analgesic and anti-inflammatory drug, an anti-inflammatory drug, a cardiotonic drug, an antifungal drug, an adrenocortical hormone drug, or a blood circulation promoting drug.
The biological patch film 10 may contain components other than regenerated cellulose and an 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 ray protection ingredient, a moisturizing ingredient, a hair growth ingredient, a cosmetic ingredient such as a cosmetic or a medicinal ingredient. Examples of the cosmetic ingredients include acacia, tragacanth, galactan, guar gum, carob gum, karaya gum, carrageenan, pectin, agar, quince seed (quince), アルゲコロイド (brown algae extract), starch (rice, corn, potato, wheat), succinoglycan, casein, albumin, gelatin, mucin, chondroitin sulfate, xylitol, maltose, sodium pyrrolidone formate, retinol, retinal, vitamin A such as retinoic acid, thiamine, riboflavin, pyridoxine, vitamin B such as folic acid, vitamin C such as ascorbic acid (sodium), vitamin D such as ergocalciferol and cholecalciferol, vitamin E such as alpha-tocopherol, vitamin K such as phylloquinone and menadione, vitamin A derivatives such as retinoic acid and palmitic acid, vitamin B derivatives such as furathiamine, and the like, Vitamin C derivatives such as glycerol ascorbate and tetrahexylsebacic acid ascorbate, vitamin D derivatives such as tachysterol, vitamin E derivatives such as alpha-tocopherol acetate, alpha-tocopheryl quinone, and alpha-tocopherol succinate, polyphenols such as hydroquinone, 4-methoxysalicylate, 4-n-butylresorcinol, and anthocyanin, disodium 3-succinylglycyrrhetinate, placenta, dihydroxy benzone, 2-ethylhexyl 4-methoxycinnamate, various amino acids, keratin, hydroxyapatite, tricalcium phosphate, calcium carbonate, ceramics such as aluminum oxide, zirconium oxide, chitin, chitosan, arbutin, ellagic acid, kojic acid, tranexamic acid, glycerol, sodium lactate, hyaluronic acid, ceramide, minoxidil, finasteride, collagen, elastin, various extracts, etc, Citric acid, lecithin, carbomer, xanthan gum, dextran, palmitic acid, lauric acid, petrolatum, titanium oxide, iron oxide, synthetic pigments, dyes, phenoxyethanol, fullerene, astaxanthin, coenzyme, human oligopeptide, glycerol, diglycerin, sorbitol, pyrrolidone carboxylic acid, polyglycerol fatty acid ester, polyglycerol, jojoba oil, trimethylglycine, mannitol, trehalose, glycosyl trehalose, pullulan, erythritol, elastin, dipropylene glycol, butylene glycol, ethyl ethylhexanoate, sodium acrylate, disodium ethylenediaminetetraacetate, sucrose fatty acid ester, squalane, polyethylene glycol, polyoxyethylene hydrogenated castor oil, glyceryl stearate, ethanol, polyvinyl alcohol, hydroxyethyl cellulose, or ectoin. Examples of the pharmaceutically effective ingredient are cepharanthine, rutin, isosorbide dinitrate, indomethacin, diflucortolone valerate, acyclovir, ketoconazole, ketoprofen, diclofenac sodium, dexamethasone propionate, felbinac, clobetasol propionate, loxoprofen, methyl salicylate, or tacrolimus. These active ingredients can be contained in the biological patch film 10 in the form of a solid, a solution, a dispersion, or an emulsion.
At least a part of the biological adhesion film 10 may be colored. For example, at least a part of the biological patch film 10 may be colored to a color close to the skin color. In this case, the skin spots, moles, and scars can be covered with the biological patch film 10 so as to be inconspicuous.
The biological adhesive film 10 can be used by being adhered to the skin at, for example, the face, the arms, and the like. Therefore, the biological patch film 10 typically has a thickness of 7mm2The above area. This makes it possible to cover a wide area when the biological adhesive film 10 is adhered to the skin. The biological adhesion membrane 10 may be attached to the surface of a living tissue other than skin, such as an organ. The organ can be protected by attaching the biological adhesion membrane 10 to the surface of the organ. For example, adhesion between organs can be prevented.
As shown in fig. 1A, the laminate 50a includes the biological adhesion film 10 and the first protective layer 21. The biological adhesive film 10 has a first main surface 11 and a second main surface 12. The second main surface 12 is located on the opposite side of the first main surface 11 in the biological adhesion film 10. The first protective layer 21 is disposed on the first main surface 11. The first protective layer 21 is a layer that can be removed from the first main surface 11. The first protective layer 21 is, for example, in contact with the first main surface 11.
The first protective layer 21 can be, for example, (i) a sheet, woven fabric, nonwoven fabric, or mesh of a polymer material such as polyethylene, polypropylene, polyethylene terephthalate, nylon, acrylic resin, polycarbonate, polyvinyl chloride, acrylonitrile/butadiene/styrene (ABS) resin, polyurethane, synthetic rubber, cellulose, テフロン (registered trademark), aramid, or polyimide, (ii) a sheet-like metal, or (iii) a sheet-like glass. The whole or a part of the surface of the first protective layer 21 may be subjected to chemical or physical surface treatment. The first protective layer 21 has a shape which is the same as or different from the shape of the biological adhesive film 10 in a plan view, and has a size which is the same as or different from the size of the biological adhesive film 10. For example, a plurality of biological adhesion films 10 may be disposed on a single first protective layer 21. The shape of the biological adhesive film 10 can be maintained even without the first protective layer 21. Therefore, even if the first protective layer 21 is removed from the first main surface 11, the shape of the biological adhesion film 10 can be maintained.
An example of a method of using the laminate 50a will be described. The biological patch film 10 is applied to, for example, the skin of the face. The biological adhesion film 10 may be adhered to the skin of the arm, or may be adhered to a biological tissue other than the skin. As shown in fig. 2A, for example, the laminate 50a is brought close to a specific part (e.g., skin) of a living body so that the second main surface 12 of the living body adhesion film 10 faces the specific part (e.g., skin) of the living body, and the second main surface 12 of the living body adhesion film 10 is brought into contact with the specific part of the living body. In this case, the wearing agent, which is a liquid or cream, may be attached to a specific part of a living body or the living body patch film 10. The wearing agent is, for example, at least 1 selected from the group consisting of an aqueous solution such as pure water, physiological saline, cosmetic water, cosmetic liquid, etc., cosmetic water containing an organic solvent, lotion, cosmetic liquid, and cream. The wearing agent contains, 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 and the viscosity decreases, thereby improving the adhesion of the biological adhesive film 10 to the skin. The wearing agent may be an aqueous solution containing a polyol. In this case, the polyol is, for example, glycerol or propylene glycol. When these aqueous solutions are used, the body patch film 10 can be easily attached to the skin for a longer period of time than when water is used. The wearing preparation contains water, oil, alcohol, emulsifier, etc., and may further contain the above 1 or more active ingredients. The wearing agent may be attached to the specific part of the living body or the living body patch film 10 before the second main surface 12 comes into contact with the specific part of the living body, or may be attached to the living body patch film 10 after the second main surface 12 comes into contact with the specific part of the living body.
Next, as shown in fig. 2B, the first protective layer 21 is peeled off from the first main surface 11 of the biological adhesive film 10. At this time, the biological adhesion film 10 is in close contact with the living tissue, and the state in which the biological adhesion film 10 is adhered to the living tissue is maintained. If the first protective layer 21 is completely peeled off, the entire first main surface 11 of the biological adhesive film 10 is exposed as shown in fig. 2C.
The laminate 50a may be modified as shown in fig. 3 as laminate 50 b. The laminate 50b is configured in the same manner as the laminate 50a, except for the case where it is specifically described. The same reference numerals are given to the same or corresponding components of the laminate 50b as or to the laminate 50a, and detailed description thereof is omitted. The description about the laminate 50a is also applicable to the laminate 50b as long as it is technically not contradictory.
As shown in fig. 3, the laminate 50b further includes a second protective layer 22. The second protective layer 22 is disposed on the second main surface 12. The second main surface 12 may be protected by a second protective layer 22. In addition, the second protective layer 22 facilitates handling of the laminate 50 b.
The material of the second protective layer 22 may be the same as that of the first protective layer 21, or may be different from that of the first protective layer 21. The second protective layer 22 has a shape that is the same as or different from the shape of the biological adhesion film 10 in a plan view, and has a size that is the same as or different from the size of the biological adhesion film 10. The second protective layer 22 has a shape which is the same as or different from the shape of the first protective layer 21 in a plan view, and has a size which is the same as or different from the size of the first protective layer 21.
The second protective layer 22 is typically removable from the second main surface 12. When the laminate 50b is used, for example, first, the second protective layer 22 is peeled off from the biological adhesion film 10. Thereby, the second main surface 12 is exposed. Then, the second main surface 12 is brought close to a specific part of a living body, and the living body sticking film 10 is stuck to the specific part of the living body in the same manner as the method of using the laminate 50 a.
An example of the method for producing the biological adhesion film 10 will be described. First, a cellulose solution is prepared by dissolving cellulose in a solvent. To obtain a regenerated cellulose film having a weight average molecular weight of 30,000 or more, cellulose having a weight average molecular weight of at least 30,000 or more is used. Thus, a self-supporting biological adhesive film having a thickness of 6500nm or less can be produced. In order to obtain a regenerated cellulose film having a weight average molecular weight of 150,000 or more, a cellulose solution may be prepared using cellulose having a weight average molecular weight of at least 150,000 or more. In this case, a self-supporting biological adhesive film having a thickness of 1300nm or less can be produced. In this way, the weight average molecular weight of the cellulose used for preparing the cellulose solution is made large, whereby more hydroxyl groups are contained in 1 molecular chain. This enables formation of a large number of intermolecular hydrogen bonds, and enables stable production of a thinner film for biological adhesion. The cellulose used for preparing the cellulose solution is not particularly limited as long as it has a desired weight average molecular weight. The cellulose used for preparing the cellulose solution may be, for example, cellulose derived from plants such as pulp and cotton, or cellulose biologically produced by bacteria. The impurity concentration in the raw material of cellulose is, for example, 10 wt% or less. It is therefore useful if the regenerated cellulose has a weight average molecular weight of 2,000,000 or less because handling becomes easy. It is further desirable that the regenerated cellulose has a weight average molecular weight of 1,000,000 or less.
The solvent is, for example, a solvent containing at least an ionic liquid (1 st solvent). By using the 1 st solvent, cellulose can be dissolved in a relatively short time. The ionic liquid is a salt composed of an anion and a cation, and can exhibit a liquid state at a temperature of 150 ℃ or lower. The ionic liquid contained in the 1 st solvent is, for example, an ionic liquid containing an amino acid or an alkyl phosphate. When the 1 st solvent contains such an ionic liquid, the cellulose can be dissolved while suppressing the decrease in molecular weight of the cellulose. In particular, since amino acids are components present in living bodies, an ionic liquid containing amino acids is advantageous for forming the biological adhesive film 10 that is safer for living bodies.
The cellulose can be dissolved using an ionic liquid that has been diluted in advance with a solvent that does not precipitate cellulose. For example, as the 1 st solvent, a mixture of an aprotic polar solvent and an ionic liquid may be used. The aprotic polar solvent is not easy to form hydrogen bonds and to precipitate cellulose.
The ionic liquid contained in the 1 st solvent is, for example, an ionic liquid represented by the following formula (II). In the ionic liquid represented by the formula (II), the anion is an amino acid. As described in the formula (II), in the ionic liquid, the anion includes a terminal carboxyl group and a terminal amino group. The cation of the ionic liquid of formula (II) may be a quaternary ammonium cation.
In the formula (II), R1～R6Independently represents a hydrogen atom or a substituent. The substituent can be alkyl, hydroxyalkyl, or phenyl. The substituents may comprise branches in the carbon chain. The substituent may include a functional group such as an amino group, a hydroxyl group, or a carboxyl group. n is for example 4 or 5.
The ionic liquid contained in the 1 st solvent may be an ionic liquid represented by the following formula (III). In the formula (III), R1、R2、R3And R4Independently represents a hydrogen atom or an alkyl group having 1 to 4 carbon atoms.
In the step of preparing the cellulose solution, a 2 nd solvent may be further added. For example, a 2 nd solvent may be further added to a mixture of cellulose having a prescribed weight average molecular weight and the 1 st solvent. The 2 nd solvent is, for example, a solvent which does not precipitate cellulose. The 2 nd solvent can be an aprotic polar solvent.
The concentration of cellulose in the cellulose solution is typically 0.2 to 15% by weight. If the cellulose concentration of the cellulose solution is 0.2 wt% or more, the biological adhesion film 10 having a strength necessary for keeping the shape thereof can be obtained while making the thickness of the biological adhesion film 10 thin. Further, if the concentration of cellulose in the cellulose solution is 15% by weight or less, precipitation of cellulose in the cellulose solution can be suppressed. The cellulose concentration of the cellulose solution may be 1 to 10% by weight. If the cellulose concentration of the cellulose solution is 1 wt% or more, the biological patch film 10 having higher strength can be obtained. If the cellulose concentration of the cellulose solution is 10% by weight or less, a stable cellulose solution with further reduced cellulose deposition can be prepared.
Next, a cellulose solution was applied to the surface of the substrate to form a liquid film on the surface of the substrate. The contact angle of the surface of the substrate to water is, for example, 70 ° or less. In this case, the cellulose solution has appropriate wettability to the substrate, and a liquid film spreading along the surface of the substrate can be stably formed. The material of the substrate is not particularly limited. The substrate typically has a non-porous structure with a smooth surface. In this case, the cellulose solution can be prevented from entering the substrate, and the biological attachment film 10 can be easily separated from the substrate in a subsequent step.
The substrate may be chemically or physically surface modified. As the substrate, for example, a substrate of a polymer material subjected to surface modification treatment such as Ultraviolet (UV) irradiation or corona treatment can be used. The method of surface modification is not particularly limited. For example, coating, surface modification, plasma treatment, sputtering, etching, or blasting (blast) of a surface modifier can be applied.
Examples of a method for forming a liquid film of a cellulose solution on a substrate include gap coating in which a predetermined gap is formed between the liquid film and the surface of the substrate by a coater or the like, slot die coating (slot die coating), spin coating, coating using a bar coater (Metering coating), gravure coating, and the like. The thickness of the film for biological adhesion can be adjusted by adjusting the thickness of the liquid film and the concentration of the cellulose solution, which are adjusted by adjusting the thickness of the passage gap, the size of the opening of the slot die, the coating speed, the rotational speed of the spin coating, the depth of the groove of the bar coater or gravure coating, the coating speed, and the like. The method for forming a liquid film of the cellulose solution on the substrate may be a casting method, screen printing using a doctor blade (squeegee), spray coating, or electrostatic spraying.
At least one of the cellulose solution and the substrate may be heated while the substrate forms a liquid film of the cellulose solution. The heating may be performed, for example, in a temperature range (e.g., 40 to 100 ℃) capable of stably maintaining the cellulose solution.
The liquid film of cellulose solution formed on the substrate may be heated. The liquid film may be heated at a temperature (for example, 50 to 200 ℃) lower than the decomposition temperature of the ionic liquid contained in the 1 st solvent. By heating the liquid film at such a temperature, a solvent (for example, the 2 nd solvent) other than the ionic liquid can be appropriately removed, and the strength of the biological adhesion film 10 tends to be high. The heating of the liquid film may be performed under a reduced pressure environment. In this case, the solvent other than the ionic liquid can be removed moderately in a shorter time at a temperature lower than the boiling point of the solvent.
After the liquid film of the cellulose solution is formed on the substrate, the liquid film may be gelled. For example, a liquid film can be gelled by exposing the liquid film to a vapor of a liquid that can be dissolved in an ionic liquid and does not dissolve cellulose, thereby obtaining a polymer gel sheet. For example, if the liquid film is left in an environment with a relative humidity of 30 to 100% RH, the ionic liquid in the liquid film comes into contact with water, and the solubility of cellulose in the liquid film decreases. This causes a part of the cellulose molecules to precipitate, and a 3-dimensional structure is formed. As a result, the liquid film gelled. The presence or absence of the gelation point can be judged by whether or not the gelled film can be picked up.
The heating of the liquid film may be performed before the gelation of the liquid film, may be performed after the gelation of the liquid film, or may be performed before or after the gelation of the liquid film.
Next, the substrate and the polymer gel sheet are immersed in a rinse solution which is a liquid that does not dissolve cellulose. In this step, the ionic liquid is removed from the polymer gel sheet. This step can be understood as a step of washing the polymer gel sheet. In this step, in addition to the ionic liquid, a part of components (for example, the 2 nd solvent) other than the cellulose and the ionic liquid, among the components contained in the cellulose solution, may be removed. The rinse solution is typically a liquid that is soluble in the ionic liquid. Examples of such liquids are water, methanol, ethanol, propanol, butanol, octanol, toluene, xylene, acetone, acetonitrile, dimethylacetamide, dimethylformamide, and dimethylsulfoxide.
Next, the polymer gel sheet is immersed in a solution of an adhesive component. In this case, the solution of the binding component may further contain the above-mentioned active ingredient. The solvent in the solution of the adhesive component is, for example, at least 1 selected from the group consisting of water, ethanol, propanol, butanol, acetone, glycerol, propylene glycol, 1, 3-butylene glycol, 1, 4-butylene glycol, diglycerol, polyethylene glycol, and polydimethylsiloxane. Instead of dipping the polymer gel sheet in a solution of the adhesive component, the adhesive component may be attached to the polymer gel sheet by spraying, vapor deposition, or coating. The polymer gel sheet may be immersed in a solution, dispersion, or emulsion containing the above active ingredient separately from the immersion in the solution of the adhesive ingredient.
Then, unnecessary components such as a solvent are removed from the polymer gel sheet. In other words, the polymer gel sheet is dried. As a method for drying the polymer gel sheet, drying methods such as natural drying, vacuum drying, heat drying, freeze drying, and supercritical drying can be applied. The drying method of the polymer gel sheet can be vacuum heating. The conditions for drying the polymer gel sheet are not particularly limited. The conditions for drying the polymer gel sheet may be selected to be sufficient time and temperature for removing the No. 2 solvent and the rinse solution. The living body attachment film 10 can be obtained by removing the solvent from the polymer gel sheet.
In the step of drying the polymer gel sheet, for example, in the case of freeze drying, a solvent which can be frozen and has a boiling point of about 100 to 200 ℃ may be used. The freeze-drying can be carried out using a solvent such as water, t-butanol, acetic acid, 1,2,2,3,3, 4-heptafluorocyclopentane, or dimethyl sulfoxide.
In the above method, the polymer gel sheet is immersed in the solution of the adhesive component before the polymer gel sheet is dried, but the step of adhering the adhesive component may be performed after the polymer gel sheet is dried. For example, a polymer sheet obtained by drying a polymer gel sheet may be immersed in a solution of an adhesive component. In this case, the solution of the binding component may further contain the above-mentioned active ingredient. Then, the impregnated polymer sheet is further dried. In this case, the adhesive component may be attached to the polymer gel sheet by spraying, vapor deposition, or coating.
