JP6908935B2 - Water-insoluble self-supporting thin film with high adhesiveness - Google Patents

Description

The present invention relates to a self-supporting thin film made of a water-insoluble polymer, surface-modified, and having high adhesive strength to an object including an organ, skin, etc., and a method for producing the same.

As a biocompatible thin film, a thin film having high adhesiveness to the skin and organs of a living body is required, and development as a biocompatible thin film of a polylactic acid thin film having biodegradability and easy thinning has been attempted. (Patent Document 1). However, since the polylactic acid thin film does not necessarily have sufficient elasticity, it is highly useful for parts and organs that do not move, but its application to parts and organs that do move is limited. Therefore, there is a demand for a biocompatible thin film having high bondability to skin, organs and the like, and having higher elasticity.

On the other hand, plastic films (polyethylene terephthalate, polyethylene naphthalate, polyimide) having a film thickness of several to several tens of μm have been developed and used. Development of a highly elastic water-insoluble polymer thin film is required. In particular, among the water-insoluble polymer thin films, polydimethylsiloxane (PDMS), which is one of the silicones composed of crosslinkable monomers, has various properties such as heat resistance, weather resistance, and stable electrical properties. (Patent Documents 2 to 4), and since it has a proven track record as a water-insoluble polymer thin film for medical use, its application is expected. However, it is extremely difficult to prepare a self-supporting thin film due to the residual stress generated during thermal cross-linking, and although attempts have been made (Patent Document 4, Non-Patent Document 1), its practicality is satisfactory. It wasn't.

It is recommended to use n-alkanes such as n-hexane or n-heptane as a solvent for forming this PDMS self-supporting thin film (Patent Document 4). In addition, Kang et al. Spin-coated PDMS diluted with n-hexane on a water-insoluble polymer layer made of a photoresist, and recovered a self-supporting PDMS sheet (thickness 77 to 2000 nm) on a jig. However, the aspect ratio by vulnerability PDMS sheet is not only achieved up to 10 ⁵ (Non-Patent Document 1). Aspect ratio exceeds 10 ^6, and a thin film made of a water-insoluble polymer thin film self produced in adaptable area and processes for industrial scale has not yet been ever reported.

Further, as a method for improving the bondability to a living body, the adhesion is improved by thinning the biocompatible film (Patent Documents 1 and 5), and the surface is modified by a polymer compound having high adhesiveness such as a polyphenol compound. (Non-Patent Document 2) and the like are known.

Furthermore, in applying PDMS thin films to medical and healthcare devices such as wearable implantable devices, high adhesion to living tissues is important, and establishment of PDMS thin films with modified surfaces and their manufacturing methods. Is required (Patent Document 3).

International pamphlet WO2008 / 050913 Japanese Unexamined Patent Publication No. 2006-181407 Japanese Unexamined Patent Publication No. 2012-181480 International Pamphlet W2012 / 055288 International Patent Application PCT / JP2016 / 082056 Specification

E. Kang et al., Adv. Mater., 25, 2167-2173 (2013) Fut (Kuo) Yang et al., The Open Surface Science Journal, 3, 115-122 (2011)

The present invention provides a self-supporting thin film composed of a water-insoluble polymer thin film, surface-modified, and having high adhesiveness to an object including an organ or skin in a living body, and a method for producing the same. Make it an issue.

The present inventors have made diligent efforts to use a solvent having a specific polarity as a solvent for dissolving the silicone thin film raw material composition (main agent) and the curing agent during the cross-linking and / or polymerization reaction in the manufacturing process of the silicone thin film. As a result, a method for producing a self-supporting thin film having high strength and adhesion to an object was established. Furthermore, we have established a method for producing a surface-modified self-supporting thin film coated with polyphenol by coating a water-insoluble self-supporting thin film such as a self-supporting thin film made of silicone and a polylactic acid self-supporting thin film with a polyphenol compound. .. As a result, by combining thinning to exhibit high adhesion and surface modification to improve adhesive strength by polyphenol coating, synergistic improvement of adhesiveness to objects including organs is brought about. We discovered that, established a manufacturing method for providing a polyphenol-coated self-supporting thin film having high adhesiveness, and completed the present invention.

Specifically, the present invention provides a polyphenol-coated self-supporting thin film in which the surface of at least one of the water-insoluble polymer thin films having adhesion by thinning is coated with polyphenol.

The thickness of the water-insoluble polymer self-supporting thin film is in the range of 30 nm to 800 μm, preferably in the range of 100 nm to 500 μm, more preferably in the range of 200 nm to 100 μm, and most preferably in the range of 300 nm to 30 μm. It may be a polyphenol-coated self-supporting thin film in the range of.

In the polyphenol coating freestanding thin film of the present invention, the result polyphenol coated self-supporting thin film is a silicone, the aspect ratio in some cases ¹⁰⁶ or more, or an area is 10 cm ² or more.

The self-supporting thin film of the present invention may be a self-supporting thin film having a film thickness of 1 μm or less and a maximum length of 1 m or more on the thin film surface.

The self-supporting thin film of the present invention may be a self-supporting thin film that does not contain pinholes.

In the polyphenol-coated self-supporting thin film of the present invention, the water-insoluble polymer film comprises silicone, polylactic acid (PLA), polyglycolic acid (PGA), glycolic acid / L-lactic copolymer and glycolic acid / DL-. Lactic acid copolymer selected from lactic acid copolymers, polylactone or lactone copolymer, poly (lactide-co-glycolide) copolymer (PLGA), polyethylene glycol (PEG) -converted PLGA, PLGA-PLA-PEG It may be selected from copolymers or alternating laminated films made of electrolyte polymers.

In the polyphenol-coated self-supporting thin film of the present invention, the silicone may be polydimethylsiloxane (PDMS).

The self-supporting thin film of the present invention may be a self-supporting thin film having high adhesion, high adhesive strength, high adhesive strength, high maximum tensile strength, low Young's modulus, and / or high permeability.

In the self-supporting thin film of the present invention, when the self-supporting thin film has a thickness of 588 nm, the adhesion is 20 times higher than that of a PDMS thin film having a thickness of 1 μm, the maximum tensile strength is 0.5 mPa or more, 158. It may be a self-supporting thin film having a stretchability of% or more, a Young ratio of 0.76 MPa or less, and / or a transparency of 96% or more in the visible light region (wavelength: 360 to 830 nm).

In the polyphenol-coated self-supporting thin film of the present invention, the polyphenol compound is a flavonoid compound such as polydopamine, tannic acid, catechin, rutin, anthocyanin, isoflavone, quercetin, hesperidin, chlorogenic acid, ellagic acid, lignan, curculin, coumarin. , Epicatechin gallate, epigalocatechin, epigalocatechin gallate and at least one selected from the group consisting of galocatechin gallate.

In the polyphenol-coated self-supporting thin film of the present invention, the polyphenol compound may be polydopamine.

Further, the present invention is a method for producing a self-supporting thin film made of a water-insoluble polymer, which is a water-insoluble polymer in an organic solvent having a solubility parameter (Hildebrand parameter) SP value in the range of 7.3 to 11.3. Provided is a manufacturing method including a step of curing a thin film raw material composition (main agent) to form a film.

In the method for producing a self-supporting thin film of the present invention, the water-insoluble polymer thin film may be selected from silicone or polylactic acid.

In the method for producing a self-supporting thin film of the present invention, the main component of the water-insoluble polymer thin film raw material composition (main agent) is selected from octamethylcyclotetrasiloxane, D-lactic acid and / or L-lactic acid. It may be at least one kind.

In the method for producing a self-supporting thin film of the present invention, the step of curing the water-insoluble polymer thin film raw material composition (main agent) to form a film is curing the water-insoluble polymer thin film raw material composition (main agent). The ratio of mass% of the agent may be about 5% (20: 1) or more.

Further, the present invention provides a method for producing a polyphenol-coated self-supporting thin film, which comprises a step of coating the surface of at least one film with polyphenol in the process of producing the self-supporting thin film.

In the method for producing a polyphenol-coated self-supporting thin film of the present invention, in the method for producing a polyphenol-coated self-supporting thin film on at least one film surface, the self-supporting thin film is laminated on a support made of a water-soluble polymer film. The step may include a step of immersing the laminated film in a solution containing polyphenol and coating the laminated film with polyphenol, and a step of peeling a self-supporting thin film coated with polyphenol from the laminated film coated with polyphenol.

Further, in the method for producing a polyphenol-coated self-supporting thin film of the present invention, in the method for producing a polyphenol-coated self-supporting thin film on both film surfaces, the self-supporting thin film is laminated on a support made of a water-soluble polymer film. The step may include a step of peeling the self-supporting thin film of the laminated film from the support, and a step of immersing the self-supporting thin film peeled from the support in a solution containing polyphenol and coating both sides of the self-supporting thin film with polyphenol. ..

In the method for producing a polyphenol-coated self-supporting thin film, the water-insoluble polymer is silicone, polylactic acid (PLA), polyglycolic acid (PGA), glycolic acid / L-lactic copolymer, and glycolic acid / DL-lactic acid. Lactic acid copolymer selected from copolymers, polylactone or lactone copolymer, poly (lactide-co-glycolide) copolymer (PLGA), polyethylene glycol (PEG) -converted PLGA, PLGA-PLA-PEG copolymer Or, it may be selected from an alternating laminated film made of an electrolyte polymer.

In the method for producing a polyphenol-coated self-supporting thin film, the silicone may be polydimethylsiloxane (PDMS).

In the method for producing a self-supporting thin film coated with polyphenol, the polyphenol is a flavonoid compound such as polydopamine, tannic acid, catechin, rutin, anthocyanin, isoflavone, quercetin, hesperidin, chlorogenic acid, ellagic acid, lignan, curculin, coumarin, and the like. It may be at least one selected from the group consisting of epicatechin gallate, epigalocatechin, epigalocatechin gallate and galocatechin gallate.

In the method for producing a polyphenol-coated self-supporting thin film, the polyphenol may be polydopamine.

The present invention also includes a step of curing a water-insoluble polymer thin film raw material composition (main agent) in an organic solvent having a solubility parameter (Hildebrand parameter) SP value in the range of 7.3 to 11.3 to form a film. Provided is a self-supporting thin film manufactured by a method for manufacturing a self-supporting thin film.

Further, the present invention provides a polyphenol-coated self-supporting thin film produced by a production method including the step of coating at least one of the film surfaces with polyphenol in the film-forming step.

The polyphenol-coated self-supporting thin film of the present invention may be a biocompatible thin film.

The self-supporting thin film of the present invention may be a self-supporting thin film in which at least one surface of the self-supporting thin film is surface-modified.

That is, the present invention may be a self-supporting thin film in which only one surface of the self-supporting thin film or both sides are surface-modified.

The film-forming method of the laminated film may be a manufacturing method further including a step of forming a laminated film containing a water-soluble polymer layer in an intermediate layer in the manufacturing step of the self-supporting thin film.

The step of forming the laminated film may be a manufacturing method by a roll-to-roll method.

The method for forming the laminated film is
A process of laminating a water-soluble polymer layer on a substrate in a roll-to-roll method to form a film.
Further, in the roll-to-roll method, an organic solvent solution of the water-insoluble polymer thin film and a curing agent is further coated on the water-soluble polymer layer laminated on the substrate, and the coating is formed. On the other hand, by performing a curing treatment, a step of forming a laminated film of a base material, a water-soluble polymer layer and a water-insoluble polymer thin film, and a step of forming a film, and
A step of dissolving the water-soluble polymer layer from a laminated film in which the base material, the water-soluble polymer layer and the water-insoluble polymer layer are laminated, and peeling the water-insoluble polymer thin film from the laminated film.
It may be a manufacturing method including.

In the method for forming a laminated film,
The base material is polyethylene terephthalate (PET),
The water-soluble polymer layer is polyvinyl alcohol (PVA).
The main component of the water-insoluble polymer thin film raw material composition (main agent) of the water-insoluble polymer thin film is octamethylcyclotetrasiloxane.
The solvent that dissolves the water-insoluble polymer thin film raw material composition (main agent) and the curing agent is a mixed solvent of hexane having a hexane content of 80% or less and a polar organic solvent.
In the step of forming the water-insoluble polymer thin film on the water-soluble polymer layer, the rotation speed of the roller is 0.2 to 1.0 m / min, and the water-insoluble polymer thin film is cured at 80 ° C. for 3 hours or more. By heating and
In the step of peeling the water-insoluble polymer thin film from the laminated film, the water-soluble polymer layer may be a film-forming method in which the water-soluble polymer layer is dissolved in water.

Furthermore, the present invention is a method for producing a self-supporting thin film composed of a water-insoluble polymer thin film having at least one surface modified, and further surface-modified during or after the process of the production method. Provided is a manufacturing method including a step of treating with an agent.

In the manufacturing method including the step of treating with the surface modifier, the step of irradiating the self-supporting thin film or the laminated film with plasma may be included before the step of treating with the surface modifier.

The method for producing a self-supporting thin film having at least one surface modified in the present invention is
It is a method for producing a self-supporting thin film composed of a water-insoluble polymer thin film and having both front and back surfaces modified. By immersing the self-supporting thin film in a solution containing a surface modifier, the surface modifier is used. The manufacturing method may include a step of processing. Further, in the present production method, a step of irradiating the self-supporting thin film produced by the production method with plasma may be included before the step of treating with the surface modifier.

Further, the present invention is a method for producing a self-supporting thin film composed of a water-insoluble polymer thin film and having only one of the front and back surfaces modified on the surface, and the laminated film is contained in a solution containing a surface modifier. Provided is a manufacturing method including a step of treating with a surface modifier by immersing in. In this manufacturing method, a step of irradiating the self-supporting thin film produced by the manufacturing method with plasma may be included before the step of treating with the surface modifier.

The method for producing a surface-modified self-supporting thin film of the present invention may be a production method in which the surface modifier is a silane coupling agent.

In the method for producing a surface-modified self-supporting thin film of the present invention, the silane coupling agent is vinyl vinyl trimethoxysilane, vinyl triethoxysilane, 2- (3,4-epylcyclohexyl) ethyltrimethoxysilane, 3 -Glysidoxypropylmethyldimethoxysilane, 3-glycidoxypropyltrimethoxysilane, 3-glycidoxypropylmethyldiethoxysilane, 3-glycidoxypropyltriethoxysilane, p-styryltrimethoxysilane, 3-methacry Loxypropylmethyldimethoxysilane, 3-methacryloxypropyltrimethoxysilane, 3-methacryloxypropylmethyldiethoxysilane, 3-methacryloxypropyltriethoxysilane, 3-acryloxypropyltrimethoxysilane, amino N-2- (amino) Ethyl) -3-aminopropylmethyldimethoxysilane, N-2- (aminoethyl) -3-aminopropyltrimethoxysilane, 3-aminopropyltrimethoxysilane, 3-aminopropyltriethoxysilane, 3-triethoxysilyl- N- (1,3-dimethyl-butylidene) propylamine, N-phenyl-3-aminopropyltrimethoxysilane, N- (vinylbenzyl) -2-aminoethyl-3-aminopropyltrimethoxysilane, isocyanurate tris- (Trimethoxysilylpropyl) isocyanurate, 3-ureidopropyltrialkoxysilane, mercapto3-mercaptopropylmethyldimethoxysilane, 3-mercaptopropyltrimethoxysilane, sulfidebis (triethoxysilylpropyl) tetrasulfide and isocyanate 3-isocyanabylpropyl It may be one or more selected from the group consisting of triethoxysilane.

The method for producing a self-supporting thin film of the present invention may be a method for producing the silane coupling agent as 3-aminopropyltriethoxysilane.

In the manufacturing method, the self-supporting thin film of the present invention may be a self-supporting thin film including a step of forming a laminated film containing a water-soluble polymer layer in an intermediate layer in the manufacturing step.

In the self-supporting thin film of the present invention, the step of forming the laminated film in the manufacturing method may be a self-supporting thin film by a roll-to-roll method.

The self-supporting thin film of the present invention is obtained in the above-mentioned manufacturing method.
A process of laminating a water-soluble polymer layer on a substrate in a roll-to-roll method to form a film.
Further, in the roll-to-roll method, the water-soluble polymer layer laminated on the substrate was coated with an organic solvent solution of the water-insoluble polymer thin film raw material composition (main agent) and a curing agent. A step of forming a coating layer and curing the coating layer to form a laminated film of a base material, a water-soluble polymer layer and a water-insoluble polymer thin film, and
A step of dissolving the water-soluble polymer layer from the laminated film in which the base material, the sacrificial layer and the water-insoluble polymer thin film are laminated, and peeling the water-insoluble polymer thin film from the laminated film.
It may be a self-supporting thin film containing.

The self-supporting thin film of the present invention is obtained in the above-mentioned manufacturing method.
The base material is polyethylene terephthalate (PET),
The water-soluble polymer layer is polyvinyl alcohol (PVA).
The main component of the water-insoluble polymer thin film raw material composition (main agent) of the water-insoluble polymer thin film is octamethylcyclotetrasiloxane.
The solvent that dissolves the water-insoluble polymer thin film raw material composition (main agent) and the curing agent is a mixed solvent of hexane having a hexane content of 80% or less and a polar organic solvent.
In the step of forming the water-insoluble polymer thin film on the water-soluble polymer layer, the rotation speed of the roller is 0.2 to 1.0 m / min, and the water-insoluble polymer thin film is cured at 80 ° C. for 3 hours or more. By heating and
In the step of peeling the water-insoluble polymer thin film from the laminated film, the water-soluble polymer layer may be a self-supporting thin film dissolved in water.

Further, the present invention is a self-supporting thin film having a high aspect ratio, which comprises a water-insoluble polymer thin film having at least one surface modified.
Provided is a self-supporting thin film produced by a manufacturing method including a step of treating with a surface modifier during or after the step in the method for manufacturing a self-supporting thin film.
In this manufacturing method, a step of irradiating the self-supporting thin film produced by the manufacturing method with plasma may be included before the step of treating with the surface modifier.

Further, the present invention is a self-surface-modified upright thin film having a high aspect ratio, which is composed of a water-insoluble polymer thin film and whose front and back surfaces are surface-modified.
Provided is a self-supporting thin film produced by a production method including a step of treating with a surface modifier by immersing the self-supporting thin film in a solution containing a surface modifier.
In this manufacturing method, a step of irradiating the self-supporting thin film produced by the manufacturing method with plasma may be included before the step of treating with the surface modifier.

Further, the present invention is a self-supporting thin film having a high aspect ratio, which is composed of a water-insoluble polymer thin film and only one of the front and back surfaces is surface-modified.
Provided is a self-supporting thin film produced by a production method including a step of treating a laminated film with a surface modifier by immersing the laminated film in a solution containing the surface modifier in the production method.
In this manufacturing method, a step of irradiating the self-supporting thin film produced by the manufacturing method with plasma may be included before the step of treating with the surface modifier.

The self-supporting thin film produced by a production method including a step of treating with the surface modifier may be a self-supporting thin film in which the surface modifier is a silane coupling agent.

In the self-supporting thin film produced by the production method including the step of treating with the surface modifier, the silane coupling agent is vinyl vinyltrimethoxysilane, vinyltriethoxysilane, 2- (3,4-epylcyclohexyl). Ethyltrimethoxysilane, 3-glycidoxypropylmethyldimethoxysilane, 3-glycidoxypropyltrimethoxysilane, 3-glycidoxypropylmethyldiethoxysilane, 3-glycidoxypropyltriethoxysilane, p-styryltri Methoxysilane, 3-methacryloxypropylmethyldimethoxysilane, 3-methacryloxypropyltrimethoxysilane, 3-methacryloxypropylmethyldiethoxysilane, 3-methacryloxypropyltriethoxysilane, 3-acryloxypropyltrimethoxysilane, amino N-2- (aminoethyl) -3-aminopropylmethyldimethoxysilane, N-2- (aminoethyl) -3-aminopropyltrimethoxysilane, 3-aminopropyltrimethoxysilane, 3-aminopropyltriethoxysilane, 3-Triethoxysilyl-N- (1,3-dimethyl-butylidene) propylamine, N-phenyl-3-aminopropyltrimethoxysilane, N- (vinylbenzyl) -2-aminoethyl-3-aminopropyltrimethoxy Silane, isocyanurate tris- (trimethoxysilylpropyl) isocyanurate, 3-ureidopropyltrialkoxysilane, mercapto3-mercaptopropylmethyldimethoxysilane, 3-mercaptopropyltrimethoxysilane, sulfidebis (triethoxysilylpropyl) tetrasulfide And isocyanate 3-isocyanoxide propyltriethoxysilane may be one or more self-supporting thin films selected from the group.

The self-supporting thin film produced by the production method including the step of treating with the surface modifier may be a self-supporting thin film in which the silane coupling agent is 3-aminopropyltriethoxysilane.

The self-supporting thin film having at least one surface modified by a production method including a step of treating with the surface modifier may be a single-layer film or a laminated film.

INDUSTRIAL APPLICABILITY According to the present invention, it is possible to provide a polyphenol-coated self-supporting thin film which is composed of a water-insoluble polymer thin film having adhesiveness, is surface-modified, has high strength and adhesiveness to an object, and a method for producing the same.

A roll-to-roll manufacturing process scheme for PDMS thin films. The figure of the photograph of the laminated film which laminated PET film which is a base material-PVA film which is a water-soluble polymer layer-PDMS film. Photograph of a self-supporting thin film supported by a tape frame (Fig. 3A) and a self-supporting thin film supported by a wire loop (Fig. 3B). The figure showing the increase in the film thickness of a PDMS thin film depending on the concentration of a PDMS solution depending on the mixing ratio of a main agent and a curing agent. The film thickness was measured with an atomic force microscope (AFM). Figure 5A: Diagram showing the results of measuring the light transmission in the visible light region (360-830 nm) of PDMS thin films of various film thicknesses (film thickness: 588 nm, 910 nm and 1595 nm). FIG. 5B: A diagram showing the average value of the results of measuring the light transmission in the visible light region at various film thicknesses of the self-supporting thin film. The figure which shows the FT-IR spectrum of the PDMS self-supporting thin film (main agent: curing agent = 10: 1) of various film thicknesses in the range of 275 to 1612 nm. The figure (n = 3) showing the result of the average value measured by the stress-strain curve of PDMS thin film (film thickness: 588 nm) and PDMS thick film (film thickness: 135 μm, film formation by casting method) with a tensile tester. ). The figure which shows the result of having measured the adhesion of the prepared PDMS self-supporting thin film (film thickness: 588 nm, 910 nm, 1595 nm) by the cross-cut method in accordance with JIS K5600-5-6 (ISO2409). FIG. 8A: A diagram showing photographs of the film before and after the peeling test for each film thickness of the PDMS thin film. Figure 8B: Average ± standard deviation of peeling rates for various film thicknesses. SEM image obtained by attaching a biocompatible polymer polylactic acid (PDLLA) thin film (film thickness: 120 nm) and PDMS thin film (film thickness: 588 nm) to an artificial skin model. Figure 9A: Polylactic acid (PDLLA) thin film (film thickness: 120 nm). Figure 9B: PDMS thin film (film thickness: 588 nm). FIG. 10A: Photomicrograph of PDMS and curing agent dissolved in 100% n-hexane to produce a self-supporting thin film by the roll-to-roll method. The formation of a large number of pinholes was observed. FIG. 10B: A photomicrograph of a self-supporting thin film prepared by dissolving PDMS and a curing agent in a mixed solvent of n-hexane: ethyl acetate = 4: 1 by a roll-to-roll method. Almost no pinhole formation was observed, and no large pinhole formation was observed. A) Figure: Surface only, and b) Figure: Diagram showing the scheme of the method of both front and back modification of PDMS self-supporting thin film with silane coupling agent. Wetting property of PDMS self-supporting thin film with pure water (0.5 minutes) when only the surface is modified with APTES (Fig. 12A upper figure: without APTES treatment, Fig. 12A lower figure: without APTES treatment) and changes in contact angle over time Represented figure (Fig. 12B). A diagram showing the wettability (0.5 minutes) of a PDMS self-supporting thin film with pure water when both front and back surfaces are modified with APTES (Fig. 13A upper figure: front surface, Fig. 13A lower figure: back surface) and the change in contact angle over time (Fig.) 13B). Results of air bulge test on the mechanical properties of PDMS self-supporting thin films with different base material: hardener ratios (base material: hardener = 5: 1 (604 nm), 10: 1 (561 nm), 20: 1 (498 nm)) The figure which represents. Figure 14A: Schematic representation of the air bulge test method for thin films. Figure 14B: Shows the change in elastic modulus caused by the change in the proportion of the curing agent in the PDMS self-supporting thin film. Figure 14C: Shows the change in elastic modulus caused by the change in the proportion of curing agent in the PDMS self-supporting thin film coated with PDA. The figure which shows the FT-IR spectrum of the PDMS self-supporting thin film of PDA-modified or unmodified (FIGS. 15A, 15B). A diagram showing the results of surface analysis by XPS of a PDMS self-supporting thin film surface-coated with the polymer material polydopamine (PDA) (Fig. 16A) and the signal intensity of N1s at a coating time of 0, 2 or 24 hours were compared. Figure (Fig. 16B, C). The figure which shows the evaluation result of the adhesive property to a living tissue depending on the film thickness. FIG. 17A: Shows the correlation between the PDMS film thickness and the adhesive energy to the surface of living tissue. Figure 17B: Shows the measurement results of the adhesive energy of a PDMS self-supporting thin film coated with PDA to the surface of living tissue. The figure which shows the in vivo fixation test of a small electronic device by a PDA-modified PDMS thin film. Figure 18A: Outline of the method of sealing an animal IC tag (2.2 mm × 10.5 mm × 0.8 mm) with a PDA-modified PDMS thin film (main agent: curing agent = 10: 1, film thickness: 561 nm). Fig. 18B: IC tag sealed with PDMS bulk (800 μm) and IC tag sealed with PDA-modified PDMS thin film were attached to the abdominal wall of the rat, and the deviation from the position where the IC tag was placed was observed by CT. Represents. Figure 18C: Shows the results of measuring the resonance frequency of an IC tag implanted in a rat with a network analyzer.

1. 1. Self-supporting thin film coated with polyphenol One of the embodiments of the present invention is a polyphenol-coated self-supporting thin film in which at least one film surface of a water-insoluble polymer thin film having adhesion by thinning is coated with polyphenol. Is. The polyphenol-coated self-supporting thin film exerts a synergistic effect on an object or an article including an organ or skin of a living body, and the adhesiveness due to the thin film and the adhesiveness due to the polyphenol film exert a synergistic effect on the object. High adhesiveness can be exhibited.

In the present specification, "thinning" means that by reducing the film thickness of the thin film or by producing a thin film having a small film thickness, these thin films can be used as the skin of a living body without using an adhesive. It refers to the state in which the film is thinly manufactured or manufactured so as to have an adhesive force to an object including an organ or an organ.

In the present specification, "adhesion" refers to a state in which two materials interact with each other across an interface and are aligned by atomic bonding or mechanical action, and "adhesion" refers to both. It refers to the energy required to peel off (Eiji Iwamura, Surface Technology 5, 260-266: 2007). That is, in the present specification, the "thin film having adhesion by thinning" has, for example, high followability due to the flexibility of the high molecular polymer forming the thin film, and is between the thin film surface and various substrates including biological tissue. A thin film capable of exhibiting high bondability on a substrate by a bond by van der Waals force, a hydrogen bond, a hydrophobic bond, or the like.

Further, in the present specification, "adhesion" refers to a state in which two surfaces are bonded by chemical or physical force or both through an adhesive, and "adhesion force" is the same type or different types. It refers to the force required to peel off the two materials after joining them between the surfaces of the materials via an adhesive substance. That is, in the present specification, adhering a self-supporting thin film coated with polyphenols containing polydopamine to an object or an article means that the interface between the polyphenol film and the self-supporting thin film is in close contact with the polyphenol film. It means that it is in close contact with an object or an article.

In the present specification, when the adhesive force and the adhesive force act synergistically to exert a strong adhesive force on an object, an article, or the like, the adhesive force is changed from "adhesive force" to "adhesive force". , And in particular, when expressing the synergistic effect of "adhesive force" and "adhesive force", it may be expressed as "adhesive force".

For example, in the case of a thin film made of silicone containing polydimethylsiloxane, the film thickness that exerts adhesion is 800 μm or less, preferably 500 μm or less, more preferably 100 μm or less, and most preferably 30. It is μm or less.

Further, in the case of the polylactic acid thin film, the film thickness at which the adhesive force is exhibited is 200 nm or less, preferably 100 nm or less, more preferably 50 nm or less, and most preferably 30 nm or less.

The lower limit of the film thickness of any of the thin films is not limited as long as it can be used as a self-supporting thin film, but is preferably 15 nm or more, more preferably 30 nm or more, and most preferably 100 nm or more. ..

The film thickness may be the film thickness of the single-layer film, or may be the film thickness of the laminated film obtained by laminating the single-layer film. The laminated film may be laminated with the same type of monolayer film, may be laminated with different types of monolayer film, or may be an alternating laminated film.

For example, since the silicone thin film has elasticity, when used as a biocompatible film, it can be applied to organs, skin, joints and the like that accompany movement. On the other hand, the polylactic acid thin film can produce a thin film having a smaller film thickness than the silicone thin film, and the adhesion is improved by thinning the film, but the elasticity is inferior to that of the silicone thin film. When used as a biocompatible thin film, for example, it can be used as a thin film to be attached to an organ or the like that does not move.

In the case of polydimethylsiloxane, which is one of the silicones used as a base material in the present invention, a thin film having a high aspect ratio can be produced by adjusting the polarity of the solvent at the time of curing to a specific range described below. Then, it can be used as a self-supporting thin film.

As used herein, "self-standing" refers to a thin film or thin film that is stable and capable of maintaining its properties and supports itself without the need for any support. It means that you can do it.

As used herein, the "aspect ratio" refers to a ratio obtained by dividing the maximum length of the thin film of the present invention on the thin film surface by the thickness. The shape of the thin film of the present invention may be any shape, but the maximum length means, for example, the diameter in the case of a thin film having a circular surface, and the length of the long side in the case of a rectangular thin film. ..

The aspect ratio of the thin film of the present invention is 10 ⁶ or more. Therefore, the aspect ratio of the thin film of the present invention may be 2x10 ⁶ or more, 3x10 ⁶ or more, 5x10 ⁶ or more, or 10x10 ⁶ or more.

As described above, the aspect ratio of the thin film of the present invention is 10 ⁶ or more. Therefore, when the thickness of the thin film of the present invention is 1 μm or less, the maximum length of the thin film surface of the present invention is 1 m or more. When the thickness of the thin film is 800 nm or less, the maximum length is 80 cm or more. When the thickness of the thin film is 600 nm or less, the maximum length is 60 cm or more. When the thickness of the thin film is 500 nm or less, the maximum length is 50 cm or more. When the thickness of the thin film is 400 nm or less, the maximum length is 40 cm or more. When the thickness of the thin film is 300 nm or less, the maximum length is 30 cm or more. When the thickness of the thin film is 200 nm or less, the maximum length is 20 cm or more. When the thickness of the thin film is 100 nm or less, the maximum length is 10 cm or more.

Further, the self-supporting thin film used as the base material of the present invention has high adhesion, light transmission, tensile strength, extensibility and elastic modulus. The modulus of elasticity is less than 1 GPa when the modulus of elasticity is measured by the air bulge test (Adv. Funct. Mater. 2009, 19, 2560-2568; Soft Matter, 2016, 12, 9202-9209). In particular, due to its high elastic modulus and high adhesion properties, when it is used as a biocompatible membrane, it can be used by being attached to organs, skin, and joints that accompany movement. In this case, it is difficult for the position shift to occur for a long period of time after the application due to the operation, and it is possible to exhibit the excellent property that the attached organs and the like can be observed through the attached thin film due to the high light transmittance. In addition, since a synthetic resin-based adhesive is not used, the onset of toxicity to the living body caused by the synthetic resin-based adhesive can be avoided, and the safety is also excellent.

By the above thinning, at least one surface of the self-supporting thin film having adhesion to an object including an organ or skin is coated with a polyphenol compound without using an adhesive, thereby improving synergistically. A polyphenol-coated self-supporting thin film having adhesiveness can be produced.

The film thickness of the polyphenol film is in the range of 2 nm to 30 μm, preferably 20 nm to 10 μm, more preferably 30 nm to 3 μm, and when the polyphenol is polydopamine, the film thickness of the polydopamine film is 2 It is in the range of nm to 60 nm, preferably 20 nm to 50 nm, more preferably 40 nm to 50 nm. When the polyphenol compound is tannin, it is in the range of 2 nm to 30 μm, preferably 20 nm to 10 μm, and more preferably 30 nm to 3 μm.

Due to these characteristics of the polyphenol-coated self-supporting thin film of the present invention, it can be used as a biocompatible thin film. In the present specification, the "biocompatible thin film" refers to a thin film that can be transplanted into a living body or attached to a living tissue or organ such as skin or an organ, a surgical wound, or the like, and is a biodegradable thin film. It can also be used as a coating for covering the device to be transplanted into the living body in the living body.

Further, the thin film of the present invention has high adhesion to biological tissues. When this high adhesion is expressed as adhesion (adhesion) energy, the adhesion (adhesion) energy is 2 μJ or more.

In the present specification, suitable water-insoluble polymer thin films include, for example, silicone water-insoluble polymer thin films, acrylonitrile-butadiene copolymer water-insoluble polymer thin films, acrylic water-insoluble polymer thin films, and epichlorohydrin-free. Biocompatibility of elastomers such as water-soluble polymer thin films, chlorosulfonated polyethylenes, chlorinated polyethylenes and urethane water-insoluble polymer thin films, and biocompatibility of polylactic acid, lactic acid copolymers, polylactones, lactone copolymers, polypeptides and the like. A polymer film can be mentioned.

Further, in the water-insoluble polymer thin film, the water-insoluble polymer film is silicone, polylactic acid (PLA), polyglycolic acid (PGA), glycolic acid / L-lactic copolymer and glycolic acid / DL-lactic acid. Lactic acid copolymers selected from copolymers, polylactones or lactone copolymers, poly (lactide-co-glycolide) copolymers (PLGA), polyethylene glycol (PEG) -ized PLGA, PLGA-PLA-PEG copolymers Or, for example, it may be selected from an alternating laminated film made of an electrolyte polymer such as a chitosan / alginic acid alternating laminated film.

Further, in the water-insoluble polymer thin film, the water-insoluble polymer film is silicone, polylactic acid (PLA), polyglycolic acid (PGA), glycolic acid / L-lactic copolymer and glycolic acid / DL-lactic acid. Lactic acid copolymers selected from copolymers, polylactones or lactone copolymers, poly (lactide-co-glycolide) copolymers (PLGA), polyethylene glycol (PEG) -ized PLGA, PLGA-PLA-PEG copolymers Alternatively, it may be selected from an alternating laminated film made of an electrolyte polymer.

Among these water-insoluble polymer thin films, the thermosetting resin-based water-insoluble polymer thin film and the photocurable resin-based water-insoluble polymer thin film are preferable in the present specification, but are not limited thereto.

Examples of the thermosetting water-insoluble polymer thin film include silicone water-insoluble polymer thin films, urethane water-insoluble polymer thin films, and fluorine-insoluble polymer thin films.

Examples of the photocurable water-insoluble polymer thin film include silicone water-insoluble polymer thin films and urethane acrylate resins.

An example of the organopolysiloxane water-insoluble polymer thin film used in the silicone water-insoluble polymer thin film will be described below.

In the present specification, the "water-insoluble polymer thin film raw material composition" is a composition containing a monomer component and / or a prepolymer component before the polymerization and / or cross-linking reaction for forming the water-insoluble polymer thin film. It refers to a product, and is generally called a "main agent" and is used. A desired water-insoluble polymer thin film can be produced by adding a curing agent to the water-insoluble polymer thin film raw material composition (main agent) and carrying out a crosslinking reaction under predetermined reaction conditions.

The water-insoluble polymer thin film of organopolysiloxane is a polymer having a structural unit represented by the following general formula 1. For example, it is obtained by treating a water-insoluble polymer thin film raw material composition (main agent) containing a cyclic siloxane compound with a curing agent described in detail below to polymerize and / or crosslink.
-[Si (R ¹ R ² ) -O]-
Equation 1

(In the formula, R ¹ and R ² are independently hydrogen atoms or unsubstituted or substituted alkyl groups, aryl groups or alkenyl groups, or hydrogen atoms.)

Examples of the alkyl group include a methyl group, an ethyl group, a propyl group, a butyl group, a cyclopentyl group, a cyclohexyl group, a cycloheptyl group and the like. Furthermore, a part may be replaced with a substituent having substantially no reactivity.

When R ¹ is a substituted or unsubstituted alkenyl group, it can be used not only as a component of the water-insoluble polymer thin film raw material composition (main agent) of the organopolysiloxane of the above formula 1 but also as a curing agent.

Among the organopolysiloxanes, polydimethylsiloxane in which both R ¹ and R ² are methyl groups is preferable, and its structure is represented by the following formula 2.

Examples of the cyclic siloxane compound include hexamethylcyclotrisiloxane, decamethylcyclopentasiloxane, dodecamethylcyclohexasiloxane, and the like, with octamethylcyclotetrasiloxane being preferred.

The curing agent can be used properly depending on the type of the main reactive group of the polysiloxane derivative. When the polysiloxane derivative has a hydrosilyl group as a main reactive group, a compound having an alkenyl group can be used, and when the polysiloxane derivative has an alkenyl group as a main reactive group, a compound having a hydrosilyl group can be used as a curing agent.

The curing agent having an alkenyl group is not particularly limited as long as it is a compound having an alkenyl group, but one containing at least two alkenyl groups in one molecule is preferable, and a polysiloxane having a linear structure having an alkenyl group, Siloxane compounds such as polysiloxane having an alkenyl group at the molecular terminal and cyclic siloxane containing an alkenyl group are particularly preferable. These compounds having an alkenyl group may be used alone or in combination of two or more.

A preferred example of the self-supporting thin film of the present invention is a single-layer film, that is, a self-supporting single-layer thin film capable of self-supporting without including a support film.

Further, the present invention can produce a pinhole-free self-supporting thin film containing no pinholes. In the present specification, a pinhole means a hole existing in a thin film having a minimum diameter of 10 μm or more, preferably a minimum hole diameter of 5 μm or more, and most preferably a minimum hole diameter of 1 μm or more. Is. Pinholes are more likely to occur when making thinner thin films.

In the production of a thin film containing no pinholes, a water-insoluble polymer thin film raw material composition (main agent) for forming the thin film and a curing agent are dissolved in a solvent having a specific polarity, and a crosslinking reaction is carried out. The solvent having the polarity of this characteristic is a solvent having a solubility parameter (Hildebrand parameter) SP value in the range of 7.3 to 11.3.

Such a solvent can be obtained, for example, by mixing n-hexane with another polar solvent. Other polar solvents mixed with this n-hexane include, for example, ethyl acetate. When a mixed solvent of n-hexane and ethyl acetate is used as a solvent for cross-linking formation, a solvent having a solubility parameter (Hildebrand parameter) SP value in the range of 7.3 to 11.3 by mixing a small amount of ethyl acetate with n-hexane. (See MG Whitesides et al., Anal. Chem., 75, 6544-6554 (2003)). For example, n-hexane / ethyl acetate = 4: 1 (v / v) and the like.

Further, as a specific material substance of the self-supporting thin film material, polylactic acid, a lactic acid copolymer, a polylactone, a lactone copolymer, a polypeptide and the like can be used as described above, and biocompatibility using these material substances. The polymer thin film having the above can be produced according to a known method (Japanese Patent Laid-Open No. 2014-140977).

That is, among the above-mentioned material substances, it is preferable to contain at least one of polylactic acid, lactic acid copolymer, polylactone or lactone copolymer. The reason for this is that the water-insoluble polymer thin film contains these compounds as a material substance, so that a water-insoluble polymer thin film having a more uniform film thickness can be stably obtained.

When polylactic acid is used as the material substance, for example, a polymer of L-lactic acid, D-lactic acid, or a lactic acid containing both of them can be used. Further, a polymer of lactide, which is a cyclic dimer of lactic acid such as L-lactide, D-lactide, and meso-lactide, may be used.

When a lactic acid copolymer is used as the material substance, a polymer of lactic acid and other monomer components can be used. Examples of the other monomer components include hydroxycarboxylic acids such as glycolic acid, 3-hydroxybutyric acid, 4-hydroxybutyric acid, 4-hydroxyvaleric acid, and 6-hydroxycaproic acid; ethylene glycol, propylene glycol, butanediol, and neo. Compounds or derivatives thereof containing multiple hydroxyl groups in the molecule such as pentyl glycol, polyethylene glycol, glycerin, pentaerythritol; succinic acid, adipic acid, sebacic acid, fumaric acid, terephthalic acid, isophthalic acid, 2,6-naphthalenedicarboxylic acid Examples thereof include compounds having a plurality of carboxylic acid groups in the molecule such as acid, 5-sodium sulfoisophthalic acid, 5-tetrabutylphosphonium sulfoisophthalic acid, or derivatives thereof. Further, the weight ratio when copolymerizing lactic acid constituting the lactic acid copolymer with other monomer components is preferably lactic acid / other monomer components = 50/50 to 99/1.

When polylactone is used as the material substance, for example, a polymer of lactone such as ε-caprolactone, δ-butyrolactone, β-methyl-δ-valerolactone, and β-propiolactone can be used.

When a lactone copolymer is used as the material substance, for example, a polymer of lactone and other monomer components can be used. Examples of the other monomer components include hydroxycarboxylic acids such as glycolic acid, 3-hydroxybutyric acid, 4-hydroxybutyric acid, 4-hydroxyvaleric acid, and 6-hydroxycaproic acid; ethylene glycol, propylene glycol, butanediol, and neo. Compounds or derivatives thereof containing multiple hydroxyl groups in the molecule such as pentyl glycol, polyethylene glycol, glycerin, pentaerythritol; succinic acid, adipic acid, sebacic acid, fumaric acid, terephthalic acid, isophthalic acid, 2,6-naphthalenedicarboxylic acid Examples thereof include compounds having a plurality of carboxylic acid groups in the molecule such as acid, 5-sodium sulfoisophthalic acid, 5-tetrabutylphosphonium sulfoisophthalic acid, or derivatives thereof. Moreover, the above-mentioned lactic acid or lactide may be used as another monomer component.
Further, the weight ratio when copolymerizing the lactone constituting the lactone copolymer with other monomer components is preferably lactone / other monomer component = 50/50 to 99/1.

When a polypeptide is used as a material, for example, polylysine, polyglutamine, polyasparagin, polyarginine, polyglutamic acid, polyaspartic acid, polyglycine, polyphenylalanine, polyalanine, polyleucine, polyisoleucine, polyvaline, etc. Polyproline, polyserine, polysleonine, polytyrosine and the like can be used. In addition, biopolymers other than polypeptides such as polysaccharides and nucleic acids can also be used.

The method for producing a self-supporting thin film of the present invention will be described in more detail in the following embodiments.

Since the self-supporting thin film of the present invention cannot be clearly defined only by the chemical structural formula, it may be represented as a self-supporting thin film specified by these manufacturing methods.

Further, the water-insoluble polymer thin film of the present invention comprises a filler, a pigment, a dye, a plasticizer, an adhesion accelerator, an impact resistant agent, a curing agent (for example, a scratch resistant agent), a coupling agent, an antioxidant and an antioxidant. / Or can contain additives such as light stabilizers.

2. Surface-modified self-supporting thin film Another embodiment of the present invention is hydrophilicity, hydrophobicity, water repellency, improvement of tensile strength, improvement of flexibility, improvement of adhesiveness and peeling resistance, impact resistance. , Durability, weather resistance, heat resistance, oxidation resistance improvement, compatibility improvement, surface smoothness increase, volume expansion rate reduction, etc. It is a sex thin film.

The surface to be surface-modified may be one surface. Further, a thin film having different characteristics between the front surface and the back surface is also included in the self-supporting thin film of the present invention. For example, it is possible to provide a self-supporting thin film in which one surface is hydrophilic and the other surface is hydrophobic.

An example of a surface modifier for surface modification is treatment with a silane coupling agent.

Examples of the silane coupling agent include, but are not limited to, vinyl vinyltrimethoxysilane, vinyltriethoxysilane, 2- (3,4-epoxycyclohexyl) ethyltrimethoxysilane, 3-glycidoxypropylmethyldimethoxysilane, 3-glycidoxypropyltrimethoxysilane, 3-glycidoxypropylmethyldiethoxysilane, 3-glycidoxypropyltriethoxysilane, p-styryltrimethoxysilane, 3-methacryloxypropylmethyldimethoxysilane, 3-methacry Loxypropyltrimethoxysilane, 3-methacryloxypropylmethyldiethoxysilane, 3-methacryloxypropyltriethoxysilane, 3-acryloxypropyltrimethoxysilane, amino N-2- (aminoethyl) -3-aminopropylmethyldimethoxy Silane, N-2- (aminoethyl) -3-aminopropyltrimethoxysilane, 3-aminopropyltrimethoxysilane, 3-aminopropyltriethoxysilane, 3-triethoxysilyl-N- (1,3-dimethyl-) Butylidene) Propylamine, N-phenyl-3-aminopropyltrimethoxysilane, N- (vinylbenzyl) -2-aminoethyl-3-aminopropyltrimethoxysilane, isocyanurate tris- (trimethoxysilylpropyl) isocyanurate, Selected from the group consisting of 3-ureidopropyltrialkoxysilane, mercapto3-mercaptopropylmethyldimethoxysilane, 3-mercaptopropyltrimethoxysilane, sulfidebis (triethoxysilylpropyl) tetrasulfide and isocyanate3-isocyandiapropyltriethoxysilane. Treatment by one or more of them can be mentioned.

For example, when the hydrophobic surface of a self-supporting thin film of polydimethylsiloxane is surface-modified to be hydrophilic, 3-aminopropyltriethoxysilane can be used as a silane coupling agent.

Further, as a pretreatment for the treatment with the silane coupling agent, the treatment with the silane coupling agent can be performed after activating the thin film surface by irradiating with plasma.

Since the surface of the self-supporting thin film surface-treated with a silane coupling agent is hydrophilic, it can be used for surface modification, suppression of adsorption of cells / proteins, dye modification, and the like.

The surface-modified self-supporting thin film can be provided as a surface-modified self-supporting thin film with a polyphenol compound. The polyphenol compound is preferably a flavonoid compound such as polydopamine, tannic acid, catechin, rutin, anthocyanin, isoflavone, quercetin, hesperidin, chlorogenic acid, ellagic acid, lignan, curculin, coumarin, epicatechin gallate, epigalocatechin. , Epigalocatechin gallate, one or more selected from the group consisting of gallocatechin gallate, more preferably a self-sustaining thin film which is polydopamine.

The polydopamine used in the present invention is a polymer obtained by oxidatively polymerizing dopamine or a salt thereof in an aqueous solvent by air oxidation or the like, and its reaction, structure and properties are described in Liebscher J et al., Langmuir 2013, 29. , 10539-10548. In addition, when tannic acid is used, a known method (D. Payra et al., Chem. Commun.,) That makes it soluble in organic solvents by introducing an alkyl group into tannic acid and makes it applicable to various coating techniques The polymer can be produced and used in accordance with 2016, 52, 312). For the other polyphenol compounds, a polymer can be prepared and used according to the method of using dopamine and tannic acid.

A method for producing a self-supporting thin film in which at least one of these surfaces is surface-treated will be described in detail below. Since the self-supporting thin film having at least one surface of the present invention surface-treated cannot be completely specified only by the chemical structural formula, it may be represented as a self-supporting thin film specified by these manufacturing methods. be.

3. 3. Method for Producing Self-supporting Thin Film Another embodiment of the present invention is the method for manufacturing the self-supporting thin film.

The method for producing a self-supporting thin film is a method for manufacturing a self-supporting thin film composed of a water-insoluble polymer thin film having a high aspect ratio, and the solubility parameter (Hildebrand parameter) SP value is in the range of 7.3 to 11.3. This is a production method including a step of curing a water-insoluble polymer thin film raw material composition (main agent) in a solvent solution to form a film.

In the present specification, the water-insoluble polymer thin film is formed by performing a curing treatment under predetermined conditions in a mixed solvent of the water-insoluble polymer thin film raw material composition (main agent) and a curing agent. In the present specification, the term "curing agent" is used in the same meaning as the meaning of "curing agent" generally known in the art, and is added to the water-insoluble polymer thin film raw material composition (main agent). A composition containing a component for polymerizing and / or cross-linking a monomer or prepolymer which is a component of a water-insoluble polymer thin film raw material composition (main agent) under a predetermined condition in a solvent to form a polymer. It is also referred to as a "polymerization initiator" or "crosslinking agent", or may contain these.

In the method for producing a thin film of the present invention, when the organopolysiloxane is used as a component of a water-insoluble polymer thin film raw material composition (main agent), the curing agent is selected from a curing agent well known to those skilled in the art. .. As these curing agents, for example, heat-curing type organic peroxides, addition reaction type organohydrogenpolysiloxanes, condensation reaction curing type and hydrolyzable organic silicon compounds, photocuring agents and the like can be used.

Examples of this organic peroxide include di-t-butyl peroxide, dicumyl peroxide, 2,5-dimethyl-2,5-di (benzoylperoxy) hexane, and 2,5-dimethyl-2,5-di. (t-butylperoxy) hexane, 1,1-bis (t-butylperoxy) -3,5,5-trimethylcyclohexane, 2,5-dimethylhexane-2,5-dihydroxyperoxide, 2,4- Dichlorbenzoyl peroxide, t-butylcumyl peroxide, α, α'-bis (t-butylperoxy) -p-diisopropylbenzene, 2,5-dimethyl-2,5-di (t-butylperoxy) Hexane-3-benzoyl peroxide, monochlorobenzoyl peroxide, t-butylperoxybenzene, t-butylperbenzoate and the like can be mentioned.

The amount of the organic peroxide compounded varies depending on the type of the water-insoluble polymer thin film, but is usually 0.1 to 10 parts by weight, preferably 0.5 to 5 parts by weight, based on 100 parts by weight of the water-insoluble polymer thin film. .. In addition, organic peroxide is not always necessary when cross-linking by irradiating radiation.

The photocuring agent used in the present invention is a reactive functional group of a polysiloxane compound by irradiating it with active energy rays such as visible light, ultraviolet rays, infrared rays, X-rays, α-rays, β-rays or γ-rays. A compound that produces an active substance that can be crosslinked. Examples of the photocuring agent include photoinitiator initiators such as acetophenone, propiophenone or benzophenone; 1,10-diaminodecane, 4,4'-trymethylenedipiperazine, carbamate and derivatives thereof or cobalt-. Photoanion initiators such as amine complexes; Near-infrared light-absorbing cationic dyes-Near-infrared photopolymerization initiators such as borate anion complexes; Photoacids such as sulfonic acid derivatives, onium salts or carboxylic acid esters Generator; Alternatively, a photocation initiator such as a metal fluoroboros complex salt and a trifluorinated boron complex compound or a bis (perfluolalkylsulfonyl) methane metal salt can be mentioned.

The content of the curing initiator in the composition of the present invention is not particularly limited, but from the viewpoint of curability, it is preferably 0.01 to 10 parts by weight with respect to 100 parts by weight of the polysiloxane, and the cured product. From the viewpoint of physical property balance, it is more preferably 0.05 to 5.0 parts by weight.

If the amount of the curing initiator is small, it may take a long time to cure, or a sufficiently cured cured product may not be obtained. Further, if the amount of the curing initiator is large, the color remains on the cured product, the color is colored due to rapid curing, and the heat resistance and light resistance are impaired, which is not preferable.

In the curing composition containing the photocuring agent in the present invention, a sensitizer may be added in order to promote the release of the active species. The type of sensitizer is not particularly limited, and widely known ones can be used. The amount of the sensitizer added is not particularly limited, but is preferably 0.01 to 10 parts by weight, more preferably 0.02 to 5 parts by weight, based on 100 parts by weight of the polysiloxane.

Further, in order to make the thin film of the present invention a self-supporting thin film having a specific function or use, an additive can be added to the water-insoluble polymer thin film to obtain a self-supporting thin film having a specific function. .. The type of additive is not particularly limited, and examples thereof include fillers, pigments, dyes, plasticizers, adhesion promoters, impact resistant agents, curing agents, coupling agents, antioxidants and / or photostabilizers. Be done.

When organohydrogenpolysiloxane is used as the curing agent among these, a platinum-based compound may be required as a catalyst for the addition reaction. Examples of organohydrogendienepolysiloxane include copolymers of methylhydrogenpolysiloxane, tetramethyltetrahydrogencyclotetrasiloxane, methylhydrogensiloxane and dimethylsiloxane. However, the present invention is not limited to these, and may contain an alkyl group or a phenyl group other than the methyl group.

Examples of the platinum-based catalyst include platinum chloride acid, alcohol-modified platinum chloride acid, a complex of platinum and an olefin or vinyl siloxane, fine particle platinum adsorbed on a carrier such as alumina and silica, a palladium catalyst, and a rhodium catalyst. However, it is preferably a platinum compound.

In addition, these water-insoluble polymer thin film raw material compositions (main agents) and kits of curing agents thereof are commercially available, and these can be obtained and used in the production of the thin film of the present invention. Examples of these commercially available silicone water-insoluble polymer thin films and their curing agents kits are DOW CORNING ^R TORAY ^R SILPOT 184 W / C, SYLGARD ^R 184 SILICONE ELASTOMER KIT, DOW CORNING ^R QP1-20 LIQUID. SILICONE RUBBER KIT, DOW CORNING ^R QP1-30 LIQUID SILICONE RUBBER KIT, DOW CORNING ^R QP1-40 LIQUID SILICONE RUBBER KIT, DOW CORNING ^R QP1-45 LIQUID SILICONE RUBBER KIT, DOW CORNING ^R QP1-50 LIQUID ^R QP1-60 LIQUID SILICONE RUBBER KIT, DOW CORNING ^R QP1-70 LIQUID SILICONE RUBBER KIT, Dow Corning ^R QP1-70 Liquid Silicone Rubber, and SILASTIC ^R LS 5-8740 FLUOROSILICONE RUBBER (Toray Dow Corning, Tokyo), Ecoflex ^R series (Ecoflex ^R 00-10, ^{Ecoflex R} 00-30, ^{Ecoflex R} 00-50, Ecoflex ^R 00-20) (Smooth-On, Inc.) can be mentioned. These kits can be obtained and used in the production of the self-supporting thin film of the present invention.

Further, as an example of the condensation hardening type water-insoluble polymer thin film raw material composition (main agent), KE-12, KE-14, KE-17, KE-24, KE-26, KE-1414, KE-1415 and KE-1416 (Shin-Etsu Chemical Co., Ltd., Tokyo) and, as an example of the addition reaction curing type water-insoluble polymer thin film raw material composition (main agent), KE-1300T, KE-1314-2, KE-1316, KE-1600, KE-1603-A / B, KE-1606, KE-1222-A / B and KE-1241 (Shin-Etsu Chemical Co., Ltd., Tokyo) are commercially available and can be obtained. , Can be used in the production of the self-supporting thin film of the present invention.

In addition, as commercially available examples of the photocurable water-insoluble polymer thin film raw material composition (main agent), Hitaroid 7909-1, Hitaroid 7902-1, Hitaroid 7100, Hitaroid 7200, Hitaroid UV028, Hitaroid 7902A, There are Hitaroid 7975, Hitaroid 7903-B, Hitaroid 7663, Hitaroid UV251, Hitaroid UV222, Hitaroid 7927, Hitaroid 7927 and Hitaroid 7927-15 (Hitachi Kasei Co., Ltd., Tokyo). Can be used in the manufacture of.

In the present specification, the water-soluble polymer layer is used as a sacrificing layer or a supporting membrane. Both mean layers formed on the assumption that they will be removed in a later process. The former refers to a polymer film that is removed by dissolving it in water, mainly in the process of manufacturing a thin film or film, and the latter refers to a polymer film that is removed by dissolving the manufactured thin film, including when using it. In the production of the self-supporting thin film of the present invention, a laminated film containing a water-soluble sacrificial layer or a water-soluble support film in an intermediate layer is formed in the manufacturing process, and these sacrificial layers or support films are dissolved to laminate the thin film. The step of peeling the target self-supporting thin film from the film is included.

In the present specification, the water-soluble sacrificial layer and the water-soluble polymer layer of the water-soluble support membrane are not limited as long as they are soluble in water, but are usually composed of polyvinyl alcohol membranes, polyacrylic acid membranes, polymethacrylic acid membranes, and the like. Sodium alginate membrane, polyethylene oxide membrane, polyacrylamide membrane, polyvinylpyrrolidone membrane, starch membrane, carboxymethyl cellulose membrane, collagen membrane, purulan membrane, agar membrane, silicone membrane, poly 2-methacryloyloxyethyl phosphorylcholine (MPC) membrane, poly (N) -Isopropylacrylamide (PNIPAM) membrane, polyethylene glycol (PEG) membrane, etc., preferably polyvinyl alcohol membrane, polyacrylic acid membrane, starch membrane, collagen membrane, agar membrane, poly 2-methacryloyloxyethyl phosphorylcholine (MPC). Membranes, poly (N-isopropylacrylamide) (PNIPAM) membranes and the like, more preferably polyvinyl alcohol membranes, starch membranes, collagen membranes and the like, and even more preferably polyvinyl alcohol membranes.

The film thickness of the water-soluble polymer film is usually 5 nm to 1000 nm, preferably 5 nm to 500 nm, more preferably 10 nm to 300 nm, and even more preferably 10 nm to. It is 200 nm, particularly preferably 10 nm to 100 nm.

The film thickness of the water-soluble support film is usually 50 nm to 20000 nm, preferably 100 nm to 10000 nm, more preferably 200 nm to 5000 nm, and even more preferably 500 nm to 5000 nm. It is nm, particularly preferably 700 nm to 5000 nm.

Further, the self-supporting thin film of the present invention is in the form of a sheet in which the self-supporting thin film of the present invention is laminated on a flexible release sheet for the purpose of improving handleability when the thin film of the present invention is applied to an application object. It can also be used by manufacturing a laminate. More specifically, for example, based on a known method (Japanese Patent Laid-Open No. 2014-140977), an alicyclic olefin having flexibility and a single layer containing an alicyclic olefin resin layer or an alicyclic olefin of a clothes release sheet. The surface-modified self-supporting thin film of the present invention having a predetermined film thickness is laminated on the based resin layer with a water-soluble polymer film having a thickness of 20 nm to 500 μm, and the self-supporting thin film is tipped or the like. By peeling from the release sheet and applying it to the object to be applied as it is, the handleability can be improved and the product can be used. In particular, by providing the alicyclic olefin resin layer, excellent releasability can be imparted to the release sheet.

In the present specification, examples of the base material for forming the laminated film may be other than silicone or polylactic acid, and all or a part of the base material may be a metal or an oxide film thereof, silicon, silicon rubber, or silica. Or carbon materials such as glass, mica, graphite, polyethylene, polypropylene, cellophane, elastomer, alginic acid, purulan, polyvinyl alcohol, polyimide, polyolefin, polyacrylic acid, starch, gelatin, cellulose, poly 2-methacryloyloxyethyl phosphorylcholine (MPC) It is composed of a film, a polymer material such as a poly (N-isopropylacrylamide) (PNIPAM) film, a polyethylene glycol (PEG) film, and a calcium compound such as apatite.

In the present specification, as the coating method at the time of film formation, the spin coating method, the dipping method, the spray coating method, the electropolymerization method, the vapor deposition method, the vapor deposition polymerization method, the brush coating method, the blade coating method, the roller coating method and the like. A known method such as a roll-to-roll method can be used, but in terms of producing a thin film having a high aspect ratio, that is, a self-supporting water-insoluble polymer thin film having a rectangular shape and a long side. The roll-to-roll method is preferred. A commercially available device such as a gravure coater can be used to carry out the roll-to-roll method.

Since the self-supporting thin film produced by the above manufacturing method has high elasticity and transparency, it has an insulating film and a sealing film for electronic devices, a transparent protective film for displays, a wound covering material, a catheter protective film, and a contact lens. , Pacemaker protective film, endoscopic protective film, wearable implantable device substrate, cell culture substrate, etc.

4. Method for Producing Surface-Modified Self-sustaining Thin Film Another embodiment of the present invention is a method for producing a surface-modified self-supporting thin film by subjecting the self-supporting thin film to a surface modification treatment. The surface modification includes a case where both front and back surfaces of the self-supporting thin film are surface-modified and a case where only one surface is surface-modified. In either case, a PET film or the like is used as a support film, and a thin film to be a self-supporting thin film is laminated, and the surface can be modified using this laminated film.

Examples of surface modification methods include, for example, surface activation by plasma irradiation and silane coupling agent treatment for the purpose of imparting hydrophilicity, and polyphenols for the purpose of improving adhesive force, tensile strength and elastic force. Coating of compounds is mentioned, and the method of surface modification of each is described below.

(1) Surface modification for the purpose of imparting hydrophilicity
(i) When only one surface (one side) of the self-supporting thin film is surface-modified (PDMS surface activation by treatment with a silane coupling agent after plasma irradiation)
When only one surface (one side) of the self-supporting thin film is surface-modified, polyethylene terephthalate (PET) as a base material, polyvinyl alcohol (PVA) as a water-soluble polymer layer, and poly, for example, intended for surface modification. A laminated film composed of three layers of a thin film of dimethylsiloxane (PDMS) is formed according to the method for producing a self-supporting thin film, and the PDMS film is irradiated with plasma to activate the PDMS surface.

Next, the surface-treated PDMS thin film is immersed in a 3-aminopropyltriethoxysilane (APTES) solution, which is a silane coupling agent. After the silane coupling reaction has proceeded sufficiently, the water-soluble polymer layer is dissolved and the surface-modified PDMS thin film is exfoliated to selectively surface-modify one surface of the self-supporting thin film to hydrophilicity. Can be quality.

(ii) When both sides of the self-supporting thin film are surface-modified (PDMS surface activation with a silane coupling agent after plasma irradiation)
When both sides of the self-supporting thin film are surface-modified, the surface modification peels the PDMS thin film from the three-layer laminated film using a tape frame on the self-supporting thin film produced by the method for producing the self-supporting thin film. Then, the front and back surfaces can be modified by immersing the plasma in an APTES solution after irradiation. In this case, it becomes hydrophobic before the surface modification of PDMS, but becomes hydrophilic after the surface modification by APTES.

The surface of the thin film opposite to the water-soluble polymer layer of the three-layer laminate of the support layer-water-soluble polymer layer-thin film layer, which is a step in the middle of the production method described in the method for producing the self-supporting thin film. It can be produced by peeling and collecting a self-supporting thin film whose surface is modified on only one surface by dissolving the water-soluble polymer layer after surface modification.

(2) Surface modification by coating a polyphenol compound for the purpose of improving adhesive strength, tensile strength and elastic force Adhesive strength is obtained by coating the thin film produced by the method of the present invention with a polyphenol compound and surface-modifying it. A thin film having improved tensile strength and elastic force can be produced. The implementation method in the case of single-sided modification and double-sided modification will be described below.

Examples of polyphenol compounds for surface modification of the present invention include flavonoid compounds such as polydopamine, tannic acid, catechin, rutin, anthocyanin, isoflavone, quercetin, and hesperidin, and chlorogenic acid, ellagic acid, lignan, and curculin. , Quercetin, epicatechin gallate, epigalocatechin, epigalocatechin gallate, galocatechin gallate, and at least one selected from these can be selected and used.

By dissolving these polyphenol compounds in a solvent, using this as a raw material solution for polymerization, and coating a thin film made of PDMS, a thin film surface-modified with the polyphenol compound can be produced.

As a method for coating a polyphenol compound, a spin coating method, a dipping method, a spray coating method, an electropolymerization method, a vapor deposition method, a vapor deposition polymerization method, and a brush coating method, which are well known to those skilled in the art as coating methods for film formation. , Known methods such as blade coating method, roller coating method and roll-to-roll method can be used.

For example, polydopamine can be selected as the polyphenol compound, and the surface of the PDMS self-supporting thin film or polylactic acid self-supporting thin film can be coated with polydopamine by a dipping method. As shown in the examples below, the PDMS self-supporting thin film and polylactic acid self-supporting thin film coated with polydopamine have improved adhesive strength, tensile strength and elastic force in each step as compared with the case of non-coating. do. Therefore, a thin film coated with polydopamine and surface-modified can be used as a biocompatible thin film.

Further, since the surface treatment of the self-supporting thin film described above has high elasticity and transparency, as well as further improved adhesiveness, tensile strength and elasticity, an insulating film and a sealing film for electronic devices are obtained. For use in transparent protective films for displays, wound coverings, catheter protective films, contact lenses, pacemaker protective films, endoscopic protective films, wearable implantable device substrates, and cell culture substrates. , Useful.

All references referred to herein are incorporated herein by reference in their entirety. The examples described herein illustrate embodiments of the invention and should not be construed as limiting the scope of the invention.

Experimental Materials and Equipment SILPOT 184 W / C and CATALYST SILPOT (Toray Dow Corning Co., Ltd., Tokyo) were used as the siloxane monomer composition for producing a polydimethylsiloxane polymer thin film and its curing agent. Polyvinyl alcohol (PVA, Kanto Chemical Co., Inc., Tokyo) is artificially used as the sacrificial layer, and polyethylene terephthalate (PET) film (Lumirror 25T60, Panac Co., Ltd., Tokyo) is artificially used as the base material of the laminated film. BIO SKIN PLATE (Bulux Co., Ltd., Saitama) was used as a skin model, and 3-aminopropyltriethoxysilane (APTES) solution (Tokyo Kasei Kogyo Co., Ltd., Tokyo) was used as a silane coupling agent. In addition, the organic solvent used was of a grade higher than that of a commercially available special grade product.

A gravure coater (ML-120 type, Yasui Seiki Co., Ltd., Tokyo) was used as the gravure coater used for film formation by the roll-to-roll method. A tensile tester (EZ-S type, Shimadzu Corporation, Kyoto) is used to measure the stress-strain curve, and an ultraviolet-visible spectroscopic altitude meter (V-670 type, JASCO Corporation, Tokyo) is used to test the transparency of visible light. ), The interatomic microscope used VN-8000 type (KEYENCE Co., Ltd., Tokyo), and the scanning electron microscope used VE-9800 type (KEYENCE Co., Ltd.). For plasma irradiation, a PBI-20 type irradiation device manufactured by Vacuum Device Co., Ltd. (Ibaraki) was used.

<Manufacturing of self-supporting thin film>
Using a gravure coater, polyvinyl alcohol (3 wt% aqueous solution of PVA) as a sacrificial layer was formed on the PET film. PDMS (SILPOT 184, water-insoluble polymer thin film raw material composition (main agent): curing agent = 5: 1, 10: 1, 20: 1) diluted with hexane / ethyl acetate mixed solvent (mixing ratio 4/1) Then, a film with a width of 12 cm and a length of about 10 m was formed on the PVA layer. Then, it was thermoset by heating at 80 ° C. for 12 hours or more in an oven. The above process is shown in FIG. 1, and a PET film on which PVA and PDMS are formed is shown in FIG.

A tape-shaped frame with glue on the back surface is pasted on a PET film on which PVA and PDMS have been formed, and the PVA layer is dissolved by immersing it in water heated to 60 ° C, and the frame is self-supporting. A PDMS thin film (length: 4 cm, width: 4 cm, area: 16 cm ² ) was obtained (Fig. 3). When the peeled PDMS thin film was attached onto a smooth silicon substrate and the film thickness was measured with an atomic force microscope (AFM), it was shown that the film thickness increased depending on the concentration of the PDMS solution (Fig. 4). ).

Measure the light transmittance of the prepared PDMS self-supporting thin film (thickness: 588 nm, 910 nm, 1595 nm) in the visible light region (wavelength: 360-830 nm) with an ultraviolet-visible (UV-Vis) spectrophotometer. As a result, it was shown to have a very high transparency with a transmittance of 96% or more (Fig. 5A, B).

In addition, PDMS thin films of various thicknesses (main agent: curing agent = 10: 1) were attached to a silicon fluoride substrate, and the near-infrared spectrum was measured with a near-infrared spectrophotometer. Characteristic peaks (1000 to 1100 cm ^-1 (Si-O-Si), 750 to 800 cm ^-1 , 1260 cm ^-1 (Si-CH ₃ ), 2840 to 3000 cm ^-1 (CH)) were detected. (Fig. 6).

The stress-strain curves of the PDMS self-supporting thin film (film thickness: 588 nm) and PDMS film (film thickness: 135 μm, film formation by the casting method) were measured with a tensile tester (Fig. 7). The maximum tensile strength, elongation, and Young's modulus were calculated from the measurement results (n = 3) (Table 1). As a result, the PDMS self-supporting thin film has almost the same elasticity as the thick film, but has a Young's modulus about 1.7 times lower. became. The nanosheet made of polylactic acid used as a biocompatible polymer has a film thickness of about 100 nm and a Young's modulus of about 2 GPa. The PDMS self-supporting thin film (thickness: 588 nm) is about 60 compared to a thin film (thickness: 212 nm, Young's modulus: about 45 MPa) composed of a non-thermocurable water-insoluble polymer thin film (eg SBS). It was shown to be flexible (Young's modulus ratio: 45 MPa / 0.76 MPa).

The adhesion of the prepared PDMS self-supporting thin film (film thickness: 588 nm, 910 nm, 1595 nm) was measured by the cross-cut method according to JIS K5600-5-6 (ISO2409). A right-angled grid pattern (25 squares) was formed on the PDMS self-supporting thin film attached on the SUS substrate with a cutter, and a peeling test was performed with cellophane tape with an adhesive strength of 4.0 / cm. The rate increased (Fig. 8A, B). From this result, it was shown that the PDMS thin film having a film thickness of 588 nm has about 20 times higher adhesion than the PDMS thin film having a film thickness of 1 μm or more.

Polylactic acid (PDLLA) nanosheets (film thickness: 120 nm), which are biocompatible polymers, were prepared according to known methods (Miyazaki et al., Wound Rep Reg 20 573-579 (2012)). The polylactic acid thin film and PDMS thin film (film thickness: 588 nm) were attached to an artificial skin model, and scanning electron microscope (SEM) images were acquired (FIGS. 9A and 9B). While the polylactic acid nanosheets are attached so as to cover the skin groove, the PDMS thin film follows the inside of the skin groove even though the film thickness is about 5 times that of the polylactic acid nanosheets, and is flexible. It showed high followability derived from.

In the above production method, the solvent for dissolving PDMS (SILPOT 184, water-insoluble polymer thin film raw material composition: curing agent = 10: 1) is 100% n-hexane and n-hexane: ethyl acetate. The formation of pinholes in the self-supporting thin film was compared with that when = 4: 1. When PDMS (SILPOT 184, water-insoluble polymer thin film raw material composition (main agent): curing agent = 10: 1) is dissolved in 100% n-hexane to produce a self-supporting thin film, the diameter should be 10 μm or more. The formation of a large number of pinholes was observed (Fig. 10A). On the other hand, when dissolved in n-hexane: ethyl acetate = 4: 1, pinholes were hardly formed, and even if pinholes were formed, they were small (Fig. 10B).

<Manufacturing of surface modification self-supporting thin film-surface modification of only one surface>
We attempted to modify the surface of the PDMS self-supporting thin film and tried to control the hydrophilicity using a silane coupling agent. The surface of the PDMS self-supporting thin film on the PET film was activated by irradiating it with oxygen plasma (1 minute, 30 mA). Next, the surface-treated PDMS thin film was immersed in a 3-aminopropyltriethoxysilane (APTES) solution (50 ^o C, 30 minutes). Finally, APTES was selectively modified only on the surface by peeling the PDMS self-supporting thin film from the PET film using a tape-shaped frame (Fig. 11).

<Manufacturing of surface modification self-supporting thin film-surface modification on both sides>
On the other hand, when modifying the front and back surfaces of a PDMS thin film, the PDMS thin film is first peeled from the PET film using a tape-shaped frame, irradiated with oxygen plasma, and then immersed in an APTES solution to modify the front and back surfaces with APTES. (Fig. 11).

<Manufacturing of surface-modified self-supporting thin film-surface modification of both front and back sides>
When the static contact angle was measured, the contact angle of the PDMS thin film before APTES modification was about 105 degrees on the front surface and about 103 degrees on the back surface (sacrificial layer side). Next, when the front surface of the PDMS thin film was modified with APTES, the contact angle on the APTES-treated side was about 80 degrees, and the back surface was about 98 degrees (Fig. 12A)). Furthermore, after 5 minutes, the contact angle on the APTES-treated side was about 66 degrees, and the back side was 91 degrees (Fig. 12B)). It is considered that this is because the surface hydrophilicity was improved by the amino group introduced by the APTES treatment. On the other hand, when the front and back surfaces were treated with APTES, the front surface was about 68 degrees and the back surface was about 77 degrees (Fig. 13A). Furthermore, after 5 minutes, the contact angle of the front surface was about 55 degrees and the back surface was about 61 degrees (Fig. 13B)), indicating that the front and back surfaces became hydrophilic due to the introduction of APTES.

Based on the above, we have established a method for easily modifying the front and back surfaces of PDMS thin films by using a silane coupling agent.

<Main agent: Control of mechanical properties by changing the mixing ratio of curing agent>
PDMS thin film with different base agent: curing agent ratio and almost the same film thickness (base agent: curing agent = 5: 1 (film thickness: 604 nm, elastic modulus: 194 MPa), 10: 1 (film thickness: 561 nm, elasticity) Ratio: 19 MPa), 20: 1 (film thickness: 498 nm, elastic modulus: 6 MPa)) were manufactured, and their mechanical properties were measured by an air bulge test (Fig. 14A).

As a result, the increase in the curing agent ratio showed a more remarkable increase in elastic modulus compared with a slight increase in film thickness (Fig. 14B). Even if the film thickness was almost the same, the elastic modulus increased depending on the ratio of the curing agent.

Furthermore, PDMS whose elastic modulus was improved by increasing the proportion of the curing agent was surface-treated by the PDA modification described in detail below. As a result, the PDMS thin film (main agent: curing agent = 10: 1, film thickness: 561 nm, elastic modulus: 80 MPa) modified with PDA (24 hours) was 4 compared to the unmodified thin film (modulus: 19 MPa). More than double the elastic modulus was observed, and the elastic modulus was further increased by PDA modification (Fig. 14C).

<Surface modification of PDMS thin film with polydopamine (PDA) for the purpose of improving adhesive strength>
By coating the surface of the PDMS thin film with polydopamine (PDA) (H. Lee et al., Science, 318, 426 (2007)), which is a polymer material that mimics the adhesive protein produced by mussels and other mussels, the biological tissue A water-insoluble polymer thin film having high adhesiveness to the skin was prepared. Immerse a PDMS thin film (main agent: curing agent = 10: 1, film thickness: 561 nm) in dopamine hydrochloride solution (2 mg / mL in 10 mM Tris buffer pH 8.5) for 2 hours or 24 hours under oxygen bubbling. So, the surface was modified with PDA. As a result of surface analysis by X-ray photoelectron spectroscopy (XPS), it was shown that the intensity of the nitrogen atom-derived peak (around 399 eV) of the PDA increases depending on the immersion time (Fig. 15A, B). Furthermore, when the near-infrared spectrum was measured, the characteristic peaks of the functional groups of PDA in the PDMS thin film modified with PDA by treatment for 24 hours (3745 cm ^-1 (OH), 3310 cm ^-1 (NH), 1640). cm ^-1 (C = O), 1513 cm ^-1 (Imide ring)) were detected (Figs. 16A-C).

We also investigated the effect of changing the immersion time of the PDMS thin film in the PDA solution on the film thickness of the PDA coating film. Specifically, for a PDA-modified PDMS self-supporting film having a film thickness of 600 nm, the film thickness before and after the modification was measured, and the difference is shown in Table 2 as the layer thickness of the PDA coating layer. .. As a result, there was no difference in PDA film thickness between 24 hours (44 nm) and 48 hours (43 nm), indicating that the dopamine polymerization reaction was saturated at 24 hours. In addition, it has been reported that the film thickness is less than 50 nm when the film is modified with a PDA modified for 24 hours by the immersion method on _{a SiO 2 substrate (Haeshin Lee et al., SCIENCE 19, 318, 426-430, (2007)).} .. Therefore, in the case of PDA modification by the dipping method, the film thickness is considered to be about this level in the case of 24-hour modification regardless of the substrate.

<Adhesive properties to living tissue depending on film thickness>
PDMS thin film (main agent: curing agent = 10: 1, film thickness: 561 nm, 1612 nm) or PDMS bulk film (main agent: curing agent = 10: 1, film thickness: 30 μm, 800 μm) The amount of work required for the thin film to peel off from the muscle layer when it was pulled up by a tensile tester after being attached to (chicken muscle layer) was calculated as the adhesive energy.

As a result, the adhesive (adhesive) energy to the surface of the biological tissue increases as the film thickness decreases, and the thin film (film thickness: 561 nm, adhesive energy: 10.5 μJ) is bulk (film thickness: 800 μm, adhesive energy: 2.2 μJ). ), It showed about 5 times more adhesiveness (adhesiveness) than 4 times (Fig. 17A). Furthermore, the PDMS thin film (film thickness: 561 nm, adhesive energy: 50.6 μJ) surface-modified (24 hours) by PDA showed about 5 times the adhesive (adhesive) energy before modification (Fig. 17B).

In other words, this result shows that these have a synergistic effect due to the increase in adhesiveness due to thinning and the increase in adhesiveness due to PDA modification, and show overall strong adhesive strength (adhesive strength). It is a thing.

<In vivo fixation of small electronic devices with PDA-modified PDMS thin film>
In an in vivo experiment using rats, an animal IC tag (2.2 mm x 10.5 mm x 0.8 mm, Star Engineering, ST-2.2-10.5-Si) was used as a PDA-modified PDMS thin film (main agent: curing agent = 10: 1, membrane). It was sealed with a thickness of 561 nm) and affixed to the abdominal wall (Fig. 18A).

As a result, the IC tag could be stably fixed to the abdominal wall for 30 days or more. On the other hand, when sealed with PDMS bulk (film thickness: 800 μm), it was found that the position was deviated from the position where the IC tag was first placed 6 days after implantation on the abdominal wall. Confirmed by Yamato Scientific Co., Ltd., TDM1300-IS) (Fig. 18B).

Furthermore, when the resonance frequency of the IC tag implanted in the rat was measured by a network analyzer, the resonance frequency (13.56 MHz) could be detected only by the IC tag sealed with a PDA-modified PDMS thin film and attached to the abdominal wall. On the other hand, the IC tag sealed with the bulk membrane peeled off from the abdominal wall, so the resonance frequency could not be detected (Fig. 18C).

Claims (12)

At least one surface of the water-insoluble polymer self-supporting thin film having adhesive strength is coated with a polyphenol compound, and the film thickness of the water-insoluble polymer self-supporting thin film is in the range of 30 nm to 1.612 μm. polyphenolic coated self-supporting film, characterized in that there. The water-insoluble polymer film has a lactic acid copolymer selected from silicone, polylactic acid (PLA), polyglycolic acid (PGA), glycolic acid / L-lactic acid copolymer and glycolic acid / DL-lactic acid copolymer. From coalescing, polylactone or lactone copolymers, poly (lactide-co-glycolide) copolymers (PLGA), polyethylene glycol (PEG) -converted PLGA, PLGA-PLA-PEG copolymers, or alternating laminates of electrolyte polymers The self-supporting polyphenol-coated thin film according to claim 1, characterized in that it is selected. The polyphenol-coated self-supporting thin film according to claim 1 or 2 , wherein the silicone is polydimethylsiloxane (PDMS). The polyphenol compounds include flavonoid compounds such as polydopamine, tannic acid, catechin, rutin, anthocyanin, isoflavone, quercetin, and hesperidin, chlorogenic acid, ellagic acid, lignan, curculin, coumarin, epicatechin gallate, epigallocatechin, and epigallocatechin. The polyphenol-coated self-supporting thin film according to any one of claims 1 to 3 , which is at least one selected from the group consisting of catechin gallate and gallocatechin gallate. The polyphenol-coated self-supporting thin film according to claim 3 , wherein the polyphenol compound is polydopamine. The polyphenol-coated self-supporting thin film according to any one of claims 1 to 5 , wherein the polyphenol-coated self-supporting thin film is a biocompatible thin film. A method for producing a self-supporting thin film made of a water-insoluble polymer, in which the solubility parameter (Hildebrand parameter) SP value is in the range of 7.3 to 11.3 in an organic solvent, the water-insoluble polymer thin film raw material composition (main agent). ) Is cured to form a film, which is a manufacturing method. The claim is characterized in that the component of the water-insoluble polymer thin film raw material composition (main agent) is at least one selected from octamethylcyclotetrasiloxane, D-lactic acid and / or L-lactic acid. 7. The method for producing a self-supporting thin film according to 7. In the step of curing the water-insoluble polymer thin film raw material composition (main agent) to form a film, the ratio of the mass% of the curing agent to the water-insoluble polymer thin film raw material composition (main agent) is 20: 1 (about 5). %) The production method according to any one of claims 7 or 8 , characterized in that it is equal to or greater than that. A method for producing a polyphenol-coated self-supporting thin film , wherein the production step according to claim 7 or 8 further includes a step of coating at least one film surface of the self-supporting thin film with a polyphenol compound. A method for producing a polyphenol-coated self-supporting thin film. A step of curing a water-insoluble polymer thin film raw material composition (main agent) in an organic solvent having a solubility parameter (Hildebrand parameter) SP value in the range of 7.3 to 11.3 to form a self-supporting thin film. produced by the production method comprising a thickness and wherein the range der Rukoto of 30 nm~1.612 μm, self-supporting thin film. A polyphenol-coated self-supporting thin film, which is produced by a production method including the film-forming step according to claim 11, further comprising a step of coating at least one of the film surfaces with a polyphenol compound.

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