阅读说明：本技术 生物体贴附用膜 (Film for biological adhesion ) 是由 波潟佑纪 川岛知子 青木贵裕 谷池优子 于 2019-02-07 设计创作，主要内容包括：本公开提供一种由再生纤维素构成、对肌肤的密合性优异的自支撑型的生物体贴附用膜。本公开的实施方式涉及的生物体贴附用膜,是自支撑型的生物体贴附用膜,是用于贴附于生物体的再生纤维素膜,厚度为20nm以上且2000nm以下,分子量为70,000以下的再生纤维素的比例为20％以上且90％以下,并且分子量为200,000以上的再生纤维素的比例为10％以上且80％以下。(Disclosed is a self-supporting film for biological adhesion, which is composed of regenerated cellulose and has excellent adhesion to the skin. The biological adhesion membrane according to an embodiment of the present disclosure is a self-supporting biological adhesion membrane, which is a regenerated cellulose membrane for adhesion to a biological body, and has a thickness of 20nm to 2000nm, a proportion of regenerated cellulose having a molecular weight of 70,000 or less of 20% to 90%, and a proportion of regenerated cellulose having a molecular weight of 200,000 or more of 10% to 80%.)

1. A self-supporting biological body-adhering film is a regenerated cellulose film for adhering to a biological body,

a proportion of regenerated cellulose having a molecular weight of 70,000 or less is 20% or more and 90% or less, and a proportion of regenerated cellulose having a molecular weight of 200,000 or more is 10% or more and 80% or less,

the thickness of the film for biological adhesion is 20nm to 2000 nm.

2. The film for biological adhesion according to claim 1,

the regenerated cellulose in the film for biological application has a weight average molecular weight of 100,000 or more.

3. The film for biological adhesion according to claim 1 or 2,

having a 1 x 10⁴g/m²Water vapor transmission rate of 24h or more.

4. The film for biological adhesion according to any one of claims 1 to 3,

has a crystallinity of 0% to 12%.

5. The film for biological application according to any one of claims 1 to 4,

in a spectrum obtained by measuring a fourier transform infrared spectrum of the biological patch film immersed in heavy water, a ratio of an intensity of an absorption peak associated with an OD group to an intensity of an absorption peak associated with a CH group is 0.05 or more.

6. The film for biological application according to any one of claims 1 to 5,

having a density of 0.3g/cm³Above and 1.5g/cm³The following bulk density.

7. The film for biological application according to any one of claims 1 to 6,

a component that acts on or protects a living organism is held in at least a part of the membrane.

8. The film for biological application according to any one of claims 1 to 7,

at least a portion of which is colored.

9. A laminate sheet, comprising:

the film for biological application according to any one of claims 1 to 8;

and a 1 st protective layer disposed on one main surface of the biological adhesive film,

the 1 st protective layer is removable from the one main surface.

10. The laminate sheet as set forth in claim 9,

and a 2 nd protective layer disposed on the other principal surface of the biological adhesion film.

11. A method for using the film for biological adhesion according to any one of claims 1 to 8,

the film for biological adhesion is used as a sheet for beauty, protection or decoration.

12. A method of using a laminate, the method of using the laminate of claim 9 or 10,

the laminate sheet is used as a sheet for beauty, protection or decoration.

Technical Field

The present disclosure relates to a biological adhesion film made of regenerated cellulose. The present disclosure also relates to a method of using the film for biological adhesion and a method of using a laminate sheet having the film for biological adhesion.

Background

A cosmetic sheet holding components such as an ultraviolet shielding material is known. For example, patent document 1 below discloses a self-supporting sheet to be used by being attached to the skin. The self-supporting sheet described in patent document 1 includes a hydrophobic polymer layer having biocompatibility or biodegradability, is insoluble in water, and can be attached to the skin without an adhesive material.

Cellulose is known as a hydrophilic, water-insoluble, biocompatible polymer material. Cellulose is a naturally abundant organic polymer, and is a polymer material that can be obtained at low cost.

As a method for processing cellulose, there is a method of obtaining regenerated cellulose by dissolving cellulose in an aqueous acid solution, an aqueous alkali solution, an organic solvent containing a metal salt, or the like. In addition, in recent years, it has been found that cellulose can be more efficiently dissolved by an ionic liquid. For example, patent document 2 below discloses a technique for forming a separation membrane by applying a solution obtained by dissolving cellulose in an ionic liquid to a porous support.

Prior art documents

Patent document 1: japanese patent laid-open No. 2014-227389

Patent document 2: japanese Kohyo publication No. 2010-527772

Non-patent document 1: park et al, "Cellulose crystallization index: measurement techniques and the same impact on interpretive cell performance" Biotechnology for Biofuels 2010,310

Disclosure of Invention

However, in the separation membrane of patent document 2, a cellulose-containing coating layer is formed on a porous support, and it is difficult to separate the separation membrane as a single body from the porous support. A stable cellulose self-supporting film having a thickness of about several μm has not yet been obtained.

An exemplary embodiment of the present disclosure provides a self-supporting biological adhesion film for adhering to a biological regenerated cellulose film, the biological adhesion film having a thickness of 20nm or more and 2000nm or less, the film having a molecular weight of 70,000 or less and a proportion of regenerated cellulose having a molecular weight of 200,000 or more being 20% or more and 90% or less, and a proportion of regenerated cellulose having a molecular weight of 200,000 or more being 10% or more and 80% or less.

The general or specific aspects may be realized by a film, a laminate or a method. In addition, the general or specific aspects may be achieved by any combination of films, laminates and methods.

Additional effects and advantages of the disclosed embodiments will be apparent from the description and drawings. The effects and/or advantages may be provided solely by the various embodiments or features disclosed in the specification and drawings, and not all embodiments or features may be required to achieve one or more of the effects and/or advantages.

According to the embodiments of the present disclosure, a self-supporting regenerated cellulose film can be formed, and for example, a biological patch film which has high adhesion to the skin and can be comfortably attached for a long period of time can be provided.

Drawings

Fig. 1 is a schematic perspective view showing an example of a biological adhesion film holding a component acting on a living body or protecting the living body.

Fig. 2 is a diagram showing an example of use in which the biological adhesive film 100A is adhered to a part of a face.

Fig. 3 is a diagram schematically showing a differential molecular weight distribution curve of regenerated cellulose in the biological patch film.

Fig. 4 is a schematic perspective view showing a laminate sheet 100B having a cellulose film 100.

Fig. 5 is a schematic perspective view showing a state where a part of the protective layer 101 is peeled from one main surface of the cellulose film 100.

Fig. 6 is a diagram for explaining an example of interposing a liquid 300 and/or cream 302 between the cellulose film 100 and the skin 200.

Fig. 7 is a view showing a state in which the laminate sheet 100B is attached to the skin 200.

Fig. 8 is a diagram showing a state in the process of peeling the protective layer 101 from the cellulose film 100 on the skin 200.

Fig. 9 is a schematic perspective view showing a laminate sheet 100C having a cellulose film 100, a protective layer 101, and a 2 nd protective layer 102.

Fig. 10 is a schematic perspective view showing a state in which a part of the protective layer 101 is peeled off from the cellulose film 100 of the laminate sheet 100C.

Fig. 11 is a view showing a state in which a laminate of the cellulose film 100 and the 2 nd protective layer 102 is attached to the skin 200.

Fig. 12 is a view schematically showing a state in which a colored cellulose film 100b is stuck to the skin 200.

FIG. 13 is a graph showing the results of evaluation of adhesion of the samples of examples 1 to 6 and comparative example 4.

Fig. 14 is a diagram showing an example of XRD pattern of natural cellulose.

Detailed Description

An outline of an embodiment of the present disclosure is as follows.

[ item 1]

A self-supporting biological adhesion membrane which is a regenerated cellulose membrane for adhesion to a biological body, wherein the proportion of regenerated cellulose having a molecular weight of 70,000 or less is 20% or more and 90% or less, the proportion of regenerated cellulose having a molecular weight of 200,000 or more is 10% or more and 80% or less, and the thickness of the biological adhesion membrane is 20nm or more and 2000nm or less.

[ item 2]

The film for biological application according to item 1, wherein the regenerated cellulose in the film for biological application has a weight average molecular weight of 100,000 or more.

[ item 3]

The film for biological adhesion according to item 1 or 2, which comprises 1X 10⁴g/m²Water vapor transmission rate of 24h or more.

[ item 4]

The film for biological adhesion according to any one of items 1 to 3, which has a crystallinity of 0% or more and 12% or less.

[ item 5]

The film for biological adhesion according to any one of items 1 to 4, wherein a ratio of an intensity of an absorption peak related to an OD group to an intensity of an absorption peak related to a CH group in a spectrum obtained by measuring a Fourier transform infrared spectrum of the film for biological adhesion after immersion in heavy water is 0.05 or more.

[ item 6]

The film for biological adhesion according to any one of items 1 to 5, having a thickness of 0.3g/cm³Above and 1.5g/cm³The following bulk density.

[ item 7]

The film for biological adhesion according to any one of items 1 to 6, wherein a component acting on a living body or a component protecting the living body is held at least in part in the film.

[ item 8]

The film for biological adhesion according to any one of items 1 to 7, wherein at least a part of the film is colored.

[ item 9]

A laminate sheet, comprising: the film for biological adhesion according to any one of items 1 to 8; and a 1 st protective layer disposed on one main surface of the biological adhesion film, the 1 st protective layer being removable from the one main surface.

[ item 10]

The laminate sheet according to item 9, further comprising a 2 nd protective layer disposed on the other principal surface of the biological adhesion film.

[ item 11]

A method of using the film for sticking to a living body according to any one of items 1 to 8, wherein the film for sticking to a living body is used as a sheet for beauty, protection or decoration.

[ item 12]

A method of using a laminate sheet as described in item 9 or 10, the laminate sheet being used as a sheet for beauty, protection or decoration.

Hereinafter, embodiments of the present disclosure will be described in detail with reference to the drawings. The embodiments described below are merely general or specific examples. The numerical values, shapes, materials, constituent elements, arrangement and connection forms of constituent elements, steps, order of steps, and the like shown in the following embodiments are merely examples, and the present disclosure is not limited thereto. The various modes described in this specification can be combined with each other as long as no contradiction is generated. Further, among the components in the following embodiments, components that are not recited in the independent claims indicating the uppermost concept will be described as arbitrary 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 being too complicated, some elements may not be illustrated.

(self-supporting type embodiment of the film for biological adhesion)

The film for biological adhesion according to the embodiment of the present disclosure is a self-supporting film made of regenerated cellulose, and contains regenerated cellulose having a molecular weight of 70,000 or less in a proportion of 20% to 90%, and regenerated cellulose having a molecular weight of 200,000 or more in a proportion of 10% to 80%. The typical thickness of the biological adhesion film in the embodiment of the present disclosure is 20nm or more and 2000nm or less.

The thickness of the biological adhesive film may be 50nm to 1300 nm. If the thickness of the biological adhesion film is 50nm or more, a higher strength can be obtained, and handling of the biological adhesion film becomes easier. If the thickness of the biological adhesive film is 1300nm or less, the adhesion of the biological adhesive film to, for example, the skin can be improved. Therefore, the biological patch film can be stably attached to the skin or other surfaces for a long period of time. The thickness of the biological adhesion film may be 50nm or more and 1000nm or less. If the thickness of the biological patch film is 1000nm or less, the biological patch film is not noticeable when applied to the skin, for example, and thus is advantageous. The thickness of the biological adhesion film may be 500nm or more and 1000nm or less. When the thickness is 500nm or more, a film for biological application having higher strength and less cracking can be obtained. In addition, more active ingredients such as cosmetic ingredients can be retained in the biological patch film. The thickness of the biological adhesion film may be 100nm to 500 nm. If the thickness is 100nm or more, the shape of the film is favorably maintained. By setting the thickness to 500nm or less, for example, the adhesiveness to the skin of the biological adhesive film can be further improved. Therefore, the biological patch film can be stably attached to the skin or other surfaces for a long period of time. Further, by making the biological patch film thinner, the biological patch film can be made less conspicuous on the skin.

In the present specification, the term "self-supporting film" refers to a film that can maintain the form of the film without a support, and refers to a film that can be taken up without a support without damaging the film when the film is partially held by a finger, tweezers, or the like, for example. In the present specification, "regenerated cellulose" refers to cellulose that does not have the crystal structure I peculiar to natural cellulose.

The raw material of the regenerated cellulose constituting the biological patch film is not particularly limited. For example, as a raw material of regenerated cellulose, natural cellulose derived from plants or living organisms, regenerated cellulose such as cellophane, or the like can be used. Alternatively, the raw material of the regenerated cellulose may be processed cellulose such as cellulose nanofibers. The concentration of impurities in the regenerated cellulose raw material is advantageously 10% by weight or less.

In the embodiment of the present disclosure, it is advantageous if the cellulose in the biological patch film is substantially cellulose represented by the following general formula (I).

The phrase "the cellulose is substantially represented by the general formula (I)" means that 90% or more of the hydroxyl groups of the glucose residue in the cellulose remain. The ratio of hydroxyl groups in the glucose residue in cellulose can be quantified by various known methods such as X-ray photoelectron spectroscopy (XPS). The above definitions are not intended to exclude the case where the cellulose contains no branched (branched) structures at all. The artificially derived cellulose is not included in the "cellulose substantially represented by the general formula (I)". Cellulose "substantially represented by the general formula (I)" does not exclude all cellulose regenerated by derivatization. The cellulose regenerated by derivatization may be included in the cellulose substantially represented by the general formula (I).

In an embodiment of the present disclosure, the biological adhesion film 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 supported by hydrogen bonds between nanofibers constituting the cellulose fibers. Therefore, only brittle cellulose films can be obtained. In contrast, in the film made of regenerated cellulose, nanofibers are entangled to units of molecular chains, and therefore the strength of the film made of regenerated cellulose is supported by hydrogen bonds between cellulose molecular chains. That is, hydrogen bonds between units smaller than nanofibers are uniformly formed in the film made of regenerated cellulose. Therefore, compared with the case where a film is formed from a suspension obtained by dispersing fibers of natural cellulose in water or the like, a cellulose film that suppresses brittleness, has high strength and appropriate flexibility, and is difficult to break can be provided. Here, the "nanofiber" is also referred to as "nanofibrils (or microfibrils)" and is the most basic unit of cellulose molecules assembled together, and has a width of about 4nm to about 100nm, for example, a length of about 1 μm or more.

The crystal structure of cellulose can be confirmed by XRD patterns. Fig. 14 shows an example of XRD pattern (CuK α ray (50kV, 300mA)) of natural cellulose. In the XRD pattern shown in FIG. 14, peaks near 14-17 and 23, which are characteristic of the crystal structure I, appear. Regenerated cellulose is mostly of the crystal structure II, having peaks near 12 °, 20 ° and 22 °, and having no peaks near 14-17 ° and 23 °.

The biological adhesion film according to the embodiment of the present disclosure can be used by being adhered to the skin of a human face, arm, or the like, for example. The film for biological application in the embodiment of the present disclosure typically has a thickness of 7mm²The above area. If the area of the biological adhesive film is 7mm²The above is advantageous in that, when the patch is attached to the skin, a larger area can be covered. The biological adhesive film of the present disclosure can be applied to other than the skin, and can be adhered to the surface of an organ, for example. In this case, the membrane for biological adhesion can function to prevent adhesion between organs, protect organs, and the like.

When the biological patch film according to the embodiment of the present disclosure is attached to the skin, a liquid such as water or lotion, or cream may be interposed between the biological patch film and the skin. The biological patch film itself can hold a component acting on or protecting a living body, such as a cosmetic component or an active component. For example, these components may be held in voids within the film. Particularly, if the film for biological adhesion has a true density of 1.5g/cm with respect to cellulose³The low bulk density makes it easier for cosmetic ingredients and the like to penetrate into the film. Components acting on or protecting living body such as cosmetic components can be held in solid form in the hollow of membraneThe voids may be dissolved and/or dispersed in a liquid and held in the form of a solution, dispersion or cream in the voids in the film. The film for biological application in the embodiment of the present disclosure has, for example, 0.3g/cm³Above and 1.5g/cm³The following bulk density. If the bulk density is 0.3g/cm³The above is advantageous because the strength required for maintaining the shape of the cellulose film can be ensured.

Fig. 1 shows an example of a biological adhesive film holding a component acting on a living body or protecting the living body. Fig. 1 shows a substantially circular biological adhesion film 100A. This is merely an example, and the shape of the biological adhesion film 100A is not limited to the example shown in fig. 1.

The biological adhesion film 100A holds, for example, an active ingredient 170 as an ingredient acting on a living body or protecting the living body inside the film. The active ingredient may also be present on the surface of the membrane. Whether or not the living body adhesion film retains the active ingredient can be confirmed by, for example, infrared spectroscopy. Since the regenerated cellulose constituting the biological adhesion film 100A is hydrophilic, the biological adhesion film according to the embodiment of the present disclosure can retain water-soluble components. Since the cellulose molecules are amphiphilic and have both hydrophilicity and hydrophobicity, the hydrophobic component can be retained in the biological adhesion film 100A.

The active ingredient may be, for example, a whitening ingredient, an ultraviolet screening ingredient, a moisturizing ingredient, a hair growth ingredient, a cosmetic ingredient such as a cosmetic, a drug effective ingredient, or the like. Examples of the cosmetic ingredients include gum arabic, tragacanth gum, galactan, guar gum, carob gum, karaya gum, carrageenan, pectin, agar, quince seed extract (from quince seed), seaweed (brown algae extract), starch (from rice, corn, potato or wheat), succinoglucan, casein, albumin, gelatin, mucin, chondroitin sulfate, xylitol, maltitol, sodium pyrrolidone carboxylate, vitamin a (retinol, retinal, retinoic acid, etc.) and vitamin a derivatives (retinoic acid, retinol palmitate, etc.), vitamin B (thiamine, riboflavin, pyridoxine, pyridoxamine, folic acid, etc.) and vitamin B derivatives (tetrahydrofuran, etc.), vitamin C (sodium ascorbate, etc.), vitamin C derivatives (glycerin ascorbic acid, tetrahexyldecanoic acid ascorbic acid, etc.), vitamin C, etc.), Vitamin D (ergocalciferol, cholecalciferol, etc.) and vitamin D derivatives (paclitaxel, D), vitamin E (alpha-tocopherol) and vitamin E derivatives (alpha-tocopherol acetate, alpha-tocopherol quinone, alpha-tocopherol succinate, etc.), vitamin K (phylloquinone, menaquinone, etc.), polyphenols (hydroquinone, 4-methoxysalicylate, rucinol, anthocyanin, etc.), disodium 3-succinyloxyglycyrrhetinate, placenta, benzophenone, 2-ethylhexyl 4-methoxycinnamate, various amino acids, keratin, hydroxyapatite, tricalcium phosphate, calcium carbonate, ceramics (alumina, zirconia, etc.), 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, vaseline, titanium oxide, iron oxide, synthetic pigments, dyes, phenoxyethanol, fullerene, astaxanthin, coenzymes, human oligopeptides, glycerol, diglycerol, sorbitol, pyrrolidone carboxylic acid, fatty acid polyglycerol, jojoba oil, trimethylglycine, mannitol, trehalose, glycosyl trehalose, amylopectin, erythritol, elastin, dipropylene glycol, butylene glycol, ethyl hexanoate, sodium acrylate, disodium ethylenediaminetetraacetate, sucrose fatty acid esters, squalane, polyethylene glycol, polyoxyethylene hydrogenated castor oil, glyceryl stearate, ethanol, polyvinyl alcohol, hydroxyethyl cellulose, and ectoin. Examples of pharmaceutically effective ingredients are cefotaxime, rutin, isosorbide dinitrate, indomethacin, diflucortolone valerate, acyclovir, ketoconazole, ketoprofen, diclofenac sodium, dexamethasone propionate, felbinac, clobetasol propionate, loxoprofen, methyl salicylate and tacrolimus. These active ingredients may be contained in the biological patch film 100A in a solid, solution, dispersion, or emulsion state.

Fig. 2 shows an example of use of the biological adhesion film 100A. Fig. 2 shows a state in which the biological patch film 100A is applied to the skin 200. Here, a part of the facial skin is exemplified as the skin 200.

As shown in the drawing, the living body patch film 100A can be used by being attached to a part of the body such as the face and the arm. Further, if the tensile strength of the biological adhesive film 100A is 23MPa or more, the biological adhesive film 100A is not easily broken even when it is attached to the skin, and the biological adhesive film 100A can be attached to the skin for a long time.

The biological adhesive film 100A may have a thickness of 1X 10⁴g/m²A water vapor transmission rate WVTR (Watervopour transmission rate) of 24h or more. If the water vapor transmission rate is 1X 10⁴g/m²When the time is 24 hours or more, moisture such as sweat is easily passed, and when the biological patch film 100A is attached to the skin, discomfort due to stuffiness and wetness can be reduced, which is advantageous. The water vapor permeability of the biological adhesive film 100A can be measured by the method of K7129-C in the same manner as for the water vapor permeability of the plastic film and the sheet.

The contact angle of the biological adhesive film 100A with respect to water is, for example, in the range of 0 ° to 30 °. The contact angle can be determined by the θ/2 method using an automatic contact angle meter DM-501 manufactured by Kyowa Kagaku K.K. When the biological adhesive film 100A exhibits a contact angle with respect to water in such a range, moisture on the skin can be rapidly absorbed by the biological adhesive film 100A, and stability and/or comfort when the biological adhesive film 100A is adhered to the skin can be improved.

As described later, the biological patch film according to the embodiment of the present disclosure is typically produced using two or more types of cellulose having different weight average molecular weights as raw materials, and includes regenerated cellulose having a molecular weight of 70,000 or less and regenerated cellulose having a molecular weight of 200,000 or more. Since the regenerated cellulose having a molecular weight of 200,000 or more is contained at a predetermined ratio, a self-supporting film which is thin to about 2000nm or less and is made of the regenerated cellulose can be obtained. In the embodiment of the present disclosure, the proportion of the regenerated cellulose having a molecular weight of 200,000 or more in the biological patch film is 10% or more. The long-chain cellulose contributes to an increase in the strength of the regenerated cellulose film. By mixing regenerated cellulose having a large molecular weight and regenerated cellulose having a small relative molecular weight in a membrane, a cellulose membrane which is as thin as 2000nm or less and can maintain its shape without requiring a support can be provided. Particularly, if the weight average molecular weight distribution in the biological patch film is 100,000 or more, shape maintenance is facilitated.

As described above, the biological patch film according to the embodiment of the present disclosure contains regenerated cellulose having a molecular weight of 70,000 or less in a proportion of 20% to 90% and contains regenerated cellulose having a molecular weight of 200,000 or more in a proportion of 10% to 80%. When regenerated cellulose having a molecular weight of 70,000 or less and regenerated cellulose having a molecular weight of 200,000 or more are mixed in the film, short cellulose can be present between long-chain celluloses, the surface of the film for biological adhesion can be formed into a fine uneven surface, or the proportion of hydroxyl groups unrelated to hydrogen bonds between cellulose molecules or within molecules can be increased. This can improve the adhesion to the skin. By improving the adhesion to the skin, a film or sheet that can be comfortably attached for a long period of time can be provided.

The distribution of the molecular weight of the regenerated cellulose contained in the film for biological application can be determined by, for example, a GPC (Gel Permeation Chromatography) -MALS (Multi Angle Light Scattering) method by dissolving the film for biological application in an appropriate solvent. Fig. 3 schematically shows an example of a differential molecular weight distribution curve of regenerated cellulose in a biological patch film obtained by the GPC-MALS method. The horizontal axis of the differential molecular weight distribution curve shown in FIG. 3 represents the log of the molecular weight of the regenerated cellulose₁₀M, the vertical axis represents the slope of the integrated molecular weight distribution curve, in other words, represents per log₁₀Weight fraction of M (dw/dlog)₁₀M). The differential molecular weight distribution curve is normalized so that the area of a portion surrounded by the differential molecular weight distribution curve and the horizontal axis becomes 1.

According to the production method exemplified below, a regenerated cellulose film can be formed while suppressing a decrease in molecular weight. Therefore, by using 2 types of cellulose having different molecular weights from each other as raw materials, as schematically shown in fig. 3, 2 peaks can appear in the differential molecular weight distribution curve. The proportion of cellulose having a molecular weight within a predetermined range can be determined in the same manner as in the general method using a graph of a differential molecular weight distribution curve.

For example, the proportion of the regenerated cellulose having a molecular weight of 70,000 or less can be determined as follows. First, a differential molecular weight distribution curve relating to regenerated cellulose in a cellulose film was obtained by the GPC-MALS method. Next, the differential molecular weight distribution curve and log in the portion surrounded by the horizontal axis are obtained₁₀M is an area in the range of 70,000 or less. In FIG. 3, log is indicated by hatching with oblique lines₁₀M is in the range of 70,000 or less. The proportion of the regenerated cellulose having a molecular weight of 200,000 or more can be determined in the same manner, and log is determined in a portion surrounded by the differential molecular weight distribution curve and the horizontal axis₁₀M may be in the range of 200,000 or more. In FIG. 3, log is represented by a dot shading₁₀M is in the range of 200,000 or more.

The film for biological adhesion according to the embodiment of the present invention may have a crystallinity of 0% or more and 12% or less. A cellulose film having a crystallinity of 0% can also be obtained by the following exemplary production method. When the degree of crystallinity is 12% or less, the adhesion of the biological adhesive film to the skin can be improved by appropriately decreasing the proportion of hydroxyl groups involved in the formation of crystal forms. In addition, various functions can be added to the biological adhesion membrane by modification of the position of the hydroxyl group or the like. From the viewpoint of containing more hydroxyl groups, it is advantageous if 90% or more, more preferably 98% or more, of the molecules of the regenerated cellulose in the membrane for biological application are cellulose that has not been chemically modified, derivatized, or the like. The regenerated cellulose in the biological patch film may be uncrosslinked.

From the viewpoint of improving the adhesiveness to the skin, as will be described later with reference to examples, in the spectrum obtained by measuring the fourier transform infrared spectrum of the film for bioadhesive use after immersion in heavy water, it is advantageous that the ratio of the intensity of the absorption peak relating to the OD group to the intensity of the absorption peak relating to the CH group is 0.05 or more. By appropriately having hydroxyl groups unrelated to hydrogen bonds between or in the cellulose molecules, the adhesion of the biological adhesive film to the skin is improved. The ratio of the intensity of the absorption peak associated with the OD group to the intensity of the absorption peak associated with the CH group is more preferably 0.1 or more, and still more preferably 0.3 or more. Various functions can be added to the biological adhesive film by modification of the position of the hydroxyl group or the like.

(application example)

The biological adhesion film according to the embodiment of the present invention has high strength, and can be used, for example, by adhering to the skin as described with reference to fig. 2. According to the embodiments of the present invention, since a film for biological application having an appropriate water vapor permeability can be provided, occurrence of stuffiness and wetness can be suppressed, and the film can be used by being applied to the skin for a long time.

Fig. 4 and 5 show an example of a laminate sheet in the embodiment of the present disclosure. As shown in fig. 4, the bioadhesive film in the embodiment of the present disclosure may be provided in the form of a laminate to which a protective layer is attached. The laminate sheet 100B shown in fig. 4 has a cellulose film 100 and a protective layer 101 disposed on one principal surface of the cellulose film 100. The cellulose membrane 100 may be the above-described membrane 100A for biological adhesion, and the cellulose membrane 100 may be, for example, a membrane made of regenerated cellulose having a weight average molecular weight of 100,000 or more. Of course, fig. 4 and 5 only schematically show the laminate 100B, and do not reflect actual dimensions. For example, the thicknesses of the cellulose film 100 and the protective layer 101 are exaggerated in fig. 4 and 5. In other drawings of the present disclosure, for convenience of explanation, the cellulose film and the like may be illustrated in a size and a shape different from those of the actual case.

In this example, the cellulose membrane 100 has a substantially circular shape. The cellulose membrane 100 shown in FIG. 4 may have a diameter of about 3mm, for example. Of course, the shape of the cellulose film 100 is not limited to the example shown in fig. 4, and may be an ellipse, a polygon or an irregular shape. In addition, the cellulose film 100 and the protective layer 101 may differ in size.

Refer to fig. 5. The cellulose film 100 has main surfaces Sf and Sb, and here, a protective layer 101 is disposed on the main surface Sb side. The protective layer 101 is made of, for example, a sheet or nonwoven fabric of polyethylene, polypropylene, polyethylene terephthalate, nylon, acrylic resin, polycarbonate, polyvinyl chloride, acrylonitrile-butadiene-styrene (ABS) resin, polyurethane, synthetic rubber, cellulose, teflon (registered trademark), aramid, polyimide, or the like, or a sheet of metal, glass, or the like. Further, the whole or a part of the surface of these sheets or nonwoven fabrics may be subjected to chemical or physical surface treatment. In this example, the protective layer 101 is also circular in shape as in the cellulose film 100. However, the shapes of the cellulose film 100 and the protective layer 101 need not be uniform. For example, a plurality of cellulose films 100 may be disposed on a single protective layer 101. Further, the protective layer 101 in the laminate sheet 100B is not a support for maintaining the shape of the cellulose film 100.

As schematically shown in fig. 5, the protective layer 101 is configured to be peelable from the main surface Sb of the cellulose film 100. The cellulose film 100 has a tensile strength of, for example, 23MPa or more, and is capable of maintaining its shape even in a state where the protective layer 101 is peeled off.

Here, an example of a method of using the laminate sheet of the present disclosure will be described with reference to fig. 6 to 11.

First, the laminate sheet 100B is prepared, and as shown in fig. 6, the main surface Sf of the cellulose film 100, on which the protective layer 101 is not disposed, of the main surfaces Sf and Sb is opposed to a portion to which the laminate sheet 100B is to be attached. In this example, the main face Sf of the cellulose film 100 is made to oppose the skin 200 (e.g., a part of the skin of the face).

At this time, the liquid 300 such as water and/or the cream 302 may be applied to the main surface Sf of the cellulose film 100 or the skin 200. The liquid 300 and the cream 302 contain, for example, water, oil and fat, alcohol, an emulsifier, or the like, and may further contain 1 or more kinds of the above active ingredients.

Next, the laminate sheet 100B is brought into contact with the skin 200 in a state where the main surface Sf of the cellulose film 100 is opposed to the skin 200, whereby the laminate sheet 100B is attached to the skin 200 as shown in fig. 7. Further, as shown in fig. 8, the protective layer 101 is peeled from the main surface Sb of the cellulose film 100. By peeling the protective layer 101 from the cellulose film 100, the cellulose film 100 can be left on the skin 200 as in the example described with reference to fig. 2.

Other protective layers may also be provided on the main face Sf of the cellulose film 100. Fig. 9 shows another example of the laminate sheet. The laminate sheet 100C shown in fig. 9 has a 2 nd protective layer 102 on the principal surface of the cellulose film 100 on the side opposite to the principal surface on which the protective layer 101 is arranged. The material constituting the protective layer 102 may be the same as or different from that of the protective layer 101. The protective layer 102 may also be different in size from the cellulose film 100 or the protective layer 101. Typically, the protective layer 102 is also peelable from the cellulose film 100, similarly to the protective layer 101. The presence of the protective layer 102 makes handling of the cellulose film 100 easier.

In the case of using such a laminate sheet 100C, as shown in fig. 10, first, the protective layer 101 is peeled off from the cellulose film 100. By removing the protective layer 101, the main surface Sb of the cellulose film 100 is exposed. Then, the exposed main surface Sb is opposed to the skin 200. In this case, as in the case of the laminate sheet 100B, a liquid 300 such as water or lotion and/or cream 302 may be applied to the main surface Sb of the cellulose film 100 or the skin 200.

Next, as shown in fig. 11, a laminate of the cellulose film 100 and the 2 nd protective layer 102 is attached to the skin 200. Then, the protective layer 102 is peeled off from the main surface on the other side of the cellulose film 100, i.e., the main surface on the opposite side from the main surface Sb. By peeling off the protective layer 102, the cellulose film 100 can be left on the skin 200.

The biological patch film of the present disclosure may be colored at least in part. Fig. 12 schematically shows a state where the colored cellulose film 100b is attached to the skin 200. The cellulose film 100b may be a film obtained by coloring the cellulose film 100 described above with a dye, a pigment, or the like. By the following exemplary production method, a typically transparent regenerated cellulose film can be obtained. By using the cellulose film 100b colored in a color close to the color of the skin, the color spots, moles, scars, and the like of the skin 200 can be covered with the cellulose film 100b so as not to be conspicuous.

The biological adhesive film according to the embodiment of the present invention can function as a protective sheet for protecting the skin from external stimuli by, for example, being attached to a wound. The cellulose film 100 or 100b as the film for biological application may hold a component for medical purposes. Alternatively, if a pattern or color is provided to the cellulose film by printing or the like, the living body sticking film of the present disclosure may be used as a decorative sheet such as a tattoo sticker.

Polylactic acid has been proposed as a material for a sheet to be attached to the skin. However, polylactic acid is a hydrophobic material and is not suitable for long-term use because of concerns about moisture retention. Further, if the sheet thickness of the polylactic acid is 500nm or more, an adhesive such as an acrylic adhesive or a silicone adhesive may be necessary for application to the skin. Therefore, in applications such as attachment to the skin, the irritation of the adhesive to the skin and the water vapor transmission rate of the adhesive need to be considered.

In contrast, since the cellulose film having a thickness of 2000nm or less can be attached to the skin 200 without an adhesive, the biological patch film according to the embodiment of the present disclosure can be attached to the skin without an adhesive even if the thickness is 500nm or more, for example. The reason for this is presumed to be that the cellulose film exhibits flexibility even when it has a thickness of 500nm or more, and easily follows irregularities such as curved surfaces of cheeks, arms, and the like, and therefore, the influence of the functional groups on the surface of the cellulose film and van der waals force is larger than that of the polylactic acid film, and the adhesiveness is improved. Since the cellulose film can be attached to the skin without an adhesive, the stuffiness can be reduced, and the cellulose film 100 or 100b can be used for a long time. Further, cellulose is biocompatible, and even when it is directly attached to the skin, it is difficult to apply physical or chemical stress to the skin, and is amphiphilic and has hydrophilic properties and water-insoluble properties, and therefore, there is no fear of dissolution by moisture such as sweat, and it is excellent in durability.

The cellulose films 100, 100b may be single-layer films or laminated films formed by laminating a plurality of films. In the case where the biological attachment film has a laminated structure, the cellulose films constituting the respective layers of the laminated structure may hold different components from each other. The laminated structure constituting the biological adhesion film may include a sheet-like member made of a material other than regenerated cellulose in a part thereof.

Here, an exemplary method for producing a cellulose film that can be applied as a film for biological adhesion in the embodiment of the present disclosure will be briefly described.

First, a cellulose solution is prepared by dissolving cellulose in a solvent. As the cellulose dissolved in the solvent, either natural cellulose or regenerated cellulose can be used. In the embodiment of the present disclosure, as described in the following examples, a plurality of types of cellulose having different weight average molecular weights are dissolved in a solvent to obtain a cellulose solution. The cellulose used for preparing the cellulose solution is not particularly limited as long as it has a desired weight average molecular weight. The cellulose used for preparing the cellulose solution may be, for example, cellulose derived from plants such as pulp and cotton, or cellulose produced by organisms such as bacteria. The impurity concentration in the raw material of cellulose is, for example, 10 wt% or less. If the weight average molecular weight of the cellulose dissolved in the solvent is 2,000,000 or less, the operation becomes easy, and therefore it is useful. It is more advantageous if the weight average molecular weight of the cellulose is 1,000,000 or less.

The ionic liquid contained in the solvent is, for example, an ionic liquid represented by the following general formula (II). In the following general formula (II), R₁～R₆Independently represents a hydrogen atom or a substituent. In the ionic liquid, the anion comprises a terminal carboxyl group and a terminal amino group, as shown in the general formula (II). That is, in the ionic liquid represented by the following general formula (II), the anion is an amino acid. The cation of the ionic liquid represented by the general formula (II) may be a quaternary ammonium cation.

In the general formula (II), the substituent may contain a functional group such as an amino group, a hydroxyl group or a carboxyl group. The substituents may be alkyl, hydroxyalkyl or phenyl, and the carbon chain may contain branches. In the general formula (II), n is, for example, 4 or 5.

The ionic liquid contained in the 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 predetermined weight average molecular weight and a 1 st solvent such as an ionic liquid. The 2 nd solvent is, for example, a solvent which does not precipitate cellulose. The 2 nd solvent may be an aprotic polar solvent.

The concentration of cellulose in the cellulose solution is typically 0.2 to 15% by weight. By setting the cellulose concentration of the cellulose solution to 0.2 wt% or more, a biological adhesion membrane having a strength necessary for maintaining the shape of the cellulose membrane while reducing the thickness of the cellulose membrane can be obtained. Further, by setting the cellulose concentration of the cellulose solution to 15% by weight or less, the precipitation of cellulose in the cellulose solution can be suppressed. The cellulose concentration of the cellulose solution may be 1 to 10% by weight. By setting the concentration of cellulose in the cellulose solution to 1% by weight or more, a cellulose film having higher strength can be obtained. By setting the cellulose concentration of the cellulose solution to 10% by weight or less, a stable cellulose solution with further reduced deposition of cellulose can be prepared.

Next, a cellulose solution is applied to the substrate surface to form a liquid film on the substrate surface. The contact angle of the surface of the substrate to water is, for example, 90 ° 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 adhesion film can be easily separated from the substrate in the subsequent step.

The substrate may also be chemically or physically surface modified. As the substrate, for example, a polymer material substrate subjected to surface modification treatment such as Ultraviolet (UV) irradiation or corona treatment may be used. The method for surface modification is not particularly limited. For example, coating, surface modification, plasma treatment, sputtering, etching, sandblasting, and the like of the 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 surface of the substrate and a coater or the like, slit die coating, spin coating, coating using a bar coater (Metering and coating), gravure coating, and the like. The thickness of the liquid film on the substrate can be adjusted by adjusting the size of the gap, the size of the opening of the slit die, the coating speed, the rotational speed of the spin coating, the depth of the groove of the bar coater or the gravure, the coating speed, and the like, and the concentration of the cellulose solution, and the thickness of the finally obtained film for biological attachment can be adjusted. The method for forming a liquid film of the cellulose solution on the substrate may be a casting method, screen printing using a squeegee, spray coating, or electrostatic spraying.

At least one of the cellulose solution and the substrate may be heated when forming a liquid film of the cellulose solution on the substrate. The heating may be performed, for example, in a temperature range (e.g., 40 to 100 ℃) capable of stabilizing the cellulose solution. The liquid film of the cellulose solution formed on the substrate may be heated. The heating of the liquid film may be performed at a temperature (for example, 50 to 200 ℃) lower than the decomposition temperature of the ionic liquid contained in the 1 st solvent. By heating the liquid film at such a temperature, a solvent (for example, the 2 nd solvent or the like) other than the ionic liquid can be appropriately removed, and the strength of the biological adhesion film can be improved. The heating of the liquid film may also be performed under a reduced pressure environment. In this case, the solvent other than the ionic liquid can be removed appropriately in a shorter time at a temperature lower than the boiling point of the solvent.

After forming a liquid film of the cellulose solution on the substrate, the liquid film may be gelled. For example, a liquid film can be gelled by exposing the liquid film to a vapor of a liquid that is soluble in an ionic liquid and insoluble in 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 is lowered. Thereby, a part of the cellulose molecules is precipitated to form a three-dimensional structure. 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 taken up.

The crystallinity of the cellulose film finally obtained can be adjusted by the conditions of the gelation step. For example, if gelation is performed in an environment with a relative humidity of 60% RH or less, since gelation progresses slowly, a three-dimensional structure of cellulose molecules is easily formed stably, and crystallinity can be reduced stably. In an environment with a relative humidity of 40% RH or less, a regenerated cellulose film with further reduced crystallinity can be obtained. 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 not dissolving 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, the cellulose in the components contained in the cellulose solution and a part of the component (for example, the 2 nd solvent) other than the ionic liquid 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.

Subsequently, unnecessary components such as solvent are removed from the polymer gel sheet. In other words, the polymer gel sheet is dried. As a drying method of 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 drying conditions for the polymer gel sheet are not particularly limited. As the drying conditions for the polymer gel sheet, a time and temperature sufficient to remove the No. 2 solvent and the rinsing solution are selected.

Further, in the step of drying the polymer gel sheet, natural drying, vacuum drying or heat drying is applied, whereby a strong regenerated cellulose film having a high bulk density can be easily obtained. On the other hand, in the step of drying the polymer gel sheet, if freeze drying or supercritical drying is applied, a regenerated cellulose film having a lower bulk density is easily obtained as compared with the case of applying natural drying, vacuum drying or heat drying.

In the step of drying the polymer gel sheet, for example, in the case of freeze-drying, a solvent which can be frozen and has a boiling point of about 100 to 200 ℃ is used. For example, 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. It is advantageous if the solvent used for freeze-drying is a solvent that can be dissolved in the rinsing liquid. However, even if the solvent used for freeze-drying is a solvent that is not soluble in the rinse solution, freeze-drying can be performed by replacing the rinse solution in the polymer gel sheet with a solvent that is soluble in the rinse solution after the step of immersing the polymer gel sheet in the rinse solution, and further replacing the solvent with a solvent used for freeze-drying.

By such a method, the solvent is removed from the polymer gel sheet. Through the above-described steps, a self-supporting cellulose film can be obtained.

By performing immersion into a solution, dispersion or emulsion containing an active ingredient before and/or after the step of drying the polymer gel sheet, a cellulose film retaining the active ingredient can be obtained. In this case, a solution containing a plurality of active ingredients may be used. The solvent in the solution is, for example, at least 1 selected from the group consisting of water, methanol, ethanol, propanol, butanol, octanol, toluene, xylene, acetone, acetonitrile, dimethylacetamide, dimethylformamide, and dimethylsulfoxide. Instead of dipping the polymer gel sheet or cellulose film in a solution containing an active ingredient, the active ingredient may be attached to the polymer gel sheet or cellulose film by spraying, vapor deposition, or coating. The polymer gel sheet or cellulose film is immersed in a solution containing an active ingredient as needed. Therefore, the impregnation of the polymer gel sheet or cellulose film into the solution containing the active ingredient can be omitted. In this case, a self-supporting regenerated cellulose membrane itself is provided as a membrane for biological adhesion.