JP6089438B2 - Method for producing hydrogel thin film and dry gel thin film - Google Patents

Description

  The present invention relates to a hydrogel thin film having sufficient adhesiveness to a living body or a biomaterial and a method for producing a dried gel thin film, which are suitable for use in medical applications or cosmetic applications.

  2. Description of the Related Art Conventionally, an adhesive sheet that is attached to a biological surface such as skin has been developed, such as a cosmetic pack sheet for beauty and a medical haptic agent. For example, Patent Document 1 discloses a sheet-shaped pack cosmetic based on a self-crosslinking alkylcellulose derivative hydrogel obtained by crosslinking an alkylcellulose derivative by irradiation with radiation.

  It is desirable not to use an adhesive on the surface in contact with the living body in the sheet for living body sticking. However, conventional bioadhesive sheets that do not use a pressure-sensitive adhesive do not have sufficient adhesion to the surface of the living body, and there is still room for improvement.

  On the other hand, Patent Document 2 discloses a method for producing a polymer self-supporting film by drying a foam film of an aqueous solution of a surface active polymer stretched on a frame. According to Patent Document 2, a polymer free-standing film having a thickness of nanometer order can be manufactured. Patent Document 2 further discloses that after the foam film of the surface active polymer compound is once dried to form a dry thin film, the polymer compound is further crosslinked by heating or the action of a crosslinking agent. In Patent Document 2, it is intended to use the produced polymer self-supporting membrane for applications such as a separation membrane, but the application to be applied to a living body is not studied at all.

  Patent Document 3 discloses that a thin film polymer structure (nanosheet) having a functional substance on both sides is stuck on the surface of the skin. In this document, the thin film polymer structure is applied to the skin while being supported on the surface of a soluble support membrane, and the soluble support membrane is dissolved after application to leave the thin film polymer structure on the skin. The technique of, is disclosed. This technique requires a complicated operation of dissolving the soluble support membrane.

Japanese Patent No. 4596774 JP 2011-143332 A WO2008 / 050913

  In Patent Document 1, a paste-like mixture containing a self-crosslinking alkylcellulose derivative and water or the like is processed into a sheet having a thickness of about 0.2 mm to 3.0 mm, and crosslinked by radiation irradiation to form a hydrogel. Obtaining a sheet is disclosed. The hydrogel sheet obtained by this method has a problem that the flexibility and adhesion to the surface of the living body to the skin and the like are poor.

  The present invention provides a thin film that can adhere to a living body or a biomaterial with sufficient strength without using an adhesive component, and that does not easily peel off even when applied to a moving uneven surface, and a method for producing the same. With the goal.

The inventor of the present invention provides a foam film of an aqueous solution containing a surfactant compound containing two or more polymerizable functional groups per molecule, or an aqueous solution containing a compound containing two or more polymerizable functional groups per molecule and a surfactant. A foam film is formed, and in the foam film, the surface active compound or a molecule of the compound is bonded by the reaction of the functional group, thereby forming a hydrogel thin film in which the foam film contains water. It has been found that the formed hydrogel thin film has sufficient adhesiveness on the skin surface and is difficult to peel off even when it is applied to a moving uneven surface. The present inventor has further found that a dried gel film obtained by drying the obtained hydrogel thin film has the same adhesiveness. Specifically, the present invention includes the following inventions.
(1) A foam film of an aqueous solution containing a surfactant compound containing two or more polymerizable functional groups in one molecule, or an aqueous foam film containing a compound containing two or more polymerizable functional groups in one molecule and a surfactant Forming a foam film at the opening of the frame;
Gelation that forms a hydrogel thin film in which the foam film contains water by cross-linking the surface active compound or molecules of the compound by bonding the functional groups in the foam film by reaction. Process,
A method for producing a hydrogel thin film.
(2) A foam film of an aqueous solution containing a surfactant compound containing two or more polymerizable functional groups in one molecule, or an aqueous foam film containing a compound containing two or more polymerizable functional groups in one molecule and a surfactant Forming a foam film at the opening of the frame;
Gelation that forms a hydrogel thin film in which the foam film contains water by cross-linking the surface active compound or molecules of the compound by bonding the functional groups in the foam film by reaction. Process,
And a drying step of drying the hydrogel thin film.

(3) The functional group is a chain polymerizable functional group,
The gelation step includes generating an active species for initiating chain polymerization in the foam film and proceeding with a binding reaction of the functional group.
Method (1).
(4) The functional group is a chain polymerizable functional group,
The gelation step includes generating an active species for initiating chain polymerization in the foam film and proceeding with a binding reaction of the functional group.
Method (2).
(5) A foam film of an aqueous solution containing a surfactant compound containing two or more polymerizable functional groups in one molecule, or a foam film of an aqueous solution containing a compound containing two or more polymerizable functional groups in one molecule and a surfactant A hydrogel thin film prepared by gelling in a state containing water by bonding the functional groups in the foam film by reaction to crosslink between the surface active compound or molecules of the compound.
(6) A dry gel thin film prepared by drying the hydrogel thin film of (5).

  When the hydrogel thin film and the dried gel thin film produced by the method of the present invention can adhere to a living body or a biomaterial with sufficient strength without using an adhesive component, and are attached to a moving uneven surface However, there is an advantageous effect that it is difficult to peel off.

FIG. 1a is a plan view of one embodiment of a frame used for foam film formation. FIG. 1 b is a plan view of the frame in a state where a hydrogel thin film or a dried gel thin film is formed by the procedure shown in FIG. 2. FIG. 2 is a schematic cross-sectional view for explaining a procedure for forming a foam film on a frame and subsequently forming a hydrogel thin film and a dry gel thin film. FIG. 3 is a schematic diagram showing that a sheet-like application article composed only of a hydrogel thin film attached to a finger joint surface changes following the shape change of the skin surface as the finger bends and stretches. It is. FIG. 4 is a schematic view showing that a sheet-like sticking article composed only of a dry gel thin film attached to the finger joint surface changes following the change in shape of the skin surface as the finger bends and stretches. FIG. FIG. 5 is a view showing an embodiment of a multi-layered sheet-like application article in which a hydrogel thin film and other layers are laminated. FIG. 6 is a view showing an embodiment of a multi-layered sheet-like sticking article in which a dried gel thin film and other layers are laminated. FIG. 7 is a view showing an embodiment of a sheet-like application article having a multilayer structure in which a hydrogel thin film and other layers are laminated and further including a support frame for fixing the periphery of the hydrogel thin film. FIG. 8 is a view showing an embodiment of a sheet-like adhesive article having a multilayer structure in which a dry gel thin film and other layers are laminated and further including a support frame for fixing the periphery of the dry gel thin film. is there. FIG. 9 is a schematic diagram showing a procedure for applying a hydrogel thin film to an object to be applied using a sheet-like application article having a hydrogel thin film and a flexible film-like support frame. FIG. 10 is a schematic diagram showing a procedure for applying a dry gel thin film to an article to be applied using a sheet-like application article having a dry gel thin film and a flexible film-like support frame.

  In the present specification, features of the present invention will be described with reference to the drawings as appropriate. In the drawings, the size and shape of each part are exaggerated for explanation, and the actual size and shape are not accurately depicted.

<Overview>
The outline of the preparation method of the hydrogel thin film and dry gel thin film of this invention is demonstrated with reference to FIG.

  As shown in FIG. 1a, a frame 10 in which at least one opening 11 is formed is prepared. The frame 10 is immersed in an aqueous solution 20 for forming a foam film (FIG. 2b) and pulled up to form the foam film 21 of the aqueous solution 20 stretched so as to close the opening 11 (FIG. 2c). By hydrolyzing the foam film 21 in a state containing water, a hydrogel thin film 22 is formed (FIG. 2d). The hydrogel thin film 22 is further dried to form a dry gel thin film 23 (FIG. 2e).

What is necessary is just to select the dimension and shape of the frame 10 for forming the foam film | membrane 21 suitably. Area is preferably 0.01～400Cm ² openings 11 formed in the frame 10, 1 to 10 cm ² is more preferable. The shape of the opening 11 is not particularly limited, and may be an arbitrary shape such as a circle or a polygon (such as a triangle or a rectangle) depending on the purpose. In particular, the shape of the opening 11 is preferably a circle or a polygon with rounded corners. In these shapes, stress applied to the periphery of the bubble film 21 can be reduced. Can be improved.

  Hereinafter, the compound for gel formation, the foam film forming step, the gelation step, and the drying step will be specifically described.

<Compound for gel formation>
In the present invention, a surface-active compound containing two or more polymerizable functional groups per molecule or a compound containing two or more polymerizable functional groups per molecule is used for gel formation.

  In the present specification, “an aqueous solution containing a surface active compound containing two or more polymerizable functional groups per molecule” and “a compound containing two or more polymerizable functional groups per molecule and an interface that can be used for foam film formation” The “aqueous solution containing an activator” may be collectively referred to as “foam film forming aqueous solution”.

  The aqueous solution for forming a foam film contains a surfactant. A surface active substance is a substance that has an action (surface activity) that dissolves in water and lowers the surface tension. In a preferred embodiment of the present invention, the compound containing two or more polymerizable functional groups per molecule includes a compound which itself dissolves in water and exhibits sufficient surface activity (ie, “surface active compound”). A foam film is formed using the aqueous solution. In another preferred embodiment of the present invention, a foam film is formed using an aqueous solution containing a surfactant in addition to a compound containing two or more polymerizable functional groups per molecule. The “compound containing two or more polymerizable functional groups per molecule” used in the latter embodiment in which the aqueous solution for forming a foam film contains a surfactant may itself have a surface activity, It may not have surface activity.

  The surface active compound or compound containing two or more polymerizable functional groups per molecule may be a high molecular compound or a low molecular compound.

Examples of the low molecular weight compound containing two or more polymerizable functional groups per molecule include polymerizable compounds such as a monomer compound that forms a polymer compound by polymerization to form a gel. The monomer compound is not particularly limited as long as it is a monomer compound having 2 or more, preferably 2 to 4 polymerizable functional groups per molecule, and specific examples include N, N′-methylenebisacrylamide and the like. Specific examples of the polymerizable functional group will be described later.

Examples of the polymer compound to which the polymerizable functional group is bonded include diethylene glycol, polyethylene glycol (polymerized with 3 or more molecules of ethylene glycol), diacrylamide, polyacrylamide (polymerized with 3 or more molecules of acrylamide), and the like. However, diethylene glycol and polyethylene glycol are preferred. All of these specific examples have surface activity. The range of the polymerization degree of polyethylene glycol is not particularly limited, but is preferably 3 or more, more preferably polyethylene glycol having a polymerizable functional group bonded thereto, and polyethylene glycol HO— (CH ₂ —CH ₂ —O having both ends unsubstituted. ) What has a polymerization degree n from which the number average molecular weight converted into _n- H becomes 200-6000 can be used conveniently.

  Two or more polymerizable functional groups may be included per molecule of the surface active compound or compound, and in particular, 2 to 4 polymerizable functional groups may be included in one molecule of the surface active compound or compound. preferable. The polymerizable functional group is bonded to the surface active compound or compound via a suitable covalent bond. The polymerizable functional group may be bonded to any position of the surface active compound or the compound, for example, may be bonded to one or both of the ends of the molecule of the linear surface active compound or the compound, You may couple | bond with the surface active compound or the side chain of a compound, and you may couple | bond with the form which interrupts a straight chain in the middle of a linear surfactant compound or a compound. In particular, it is preferable to use a surface active compound or compound having a polymerizable functional group bonded to one or both of the ends of the linear molecule, preferably both.

  Examples of the polymerizable functional group include a functional group capable of chain polymerization or sequential polymerization, and a chain polymerizable functional group is particularly preferable. As the chain-polymerizable functional group, a group that undergoes chain polymerization using an active species such as a radical, cation, or anion as an initiator can be used. As the chain polymerizable functional group, a functional group capable of unsaturated polymerization, ring-opening polymerization, and the like can be used as appropriate, and an unsaturated polymerizable functional group can be particularly preferably used.

  The unsaturated polymerizable functional group includes an unsaturated polymerizable functional group including a carbon-carbon double bond, a carbon-carbon triple bond, a carbon-oxygen double bond, a carbon-nitrogen double bond, a carbon-nitrogen triple bond, and the like. Can be used. In particular, an ethylene-based polymerizable functional group having a carbon-carbon double bond is preferable.

  Examples of the ethylene-based polymerizable functional group include an acryloyl group, a methacryloyl group, and a vinyl group.

  Specific preferred specific examples of the surface active compound containing two or more polymerizable functional groups per molecule include polyethylene glycol diacrylate, polyethylene glycol dimethacrylate, diethylene glycol dimethacrylate, diethylene glycol diacrylate and the like.

<Bubble film formation process>
A foam film formation process is a process of forming the foam film of the aqueous solution for foam film formation containing the said surface active compound or a compound in opening of a frame.

  The aqueous solution for forming a foam film is an aqueous solution containing the surfactant compound or compound in water. The concentration of the surface active compound or the compound in the aqueous solution is not particularly limited, and can be appropriately adjusted according to the type of the surface active compound or the compound so that a foam film can be formed in an appropriate frame. . Examples of the concentration of the surface active compound or the compound include 0.1 to 50% by weight.

  The thickness of the foam film can be adjusted by adjusting the pulling rate of the frame from the aqueous solution. Furthermore, after forming the foam film on the frame, it is possible to extract the aqueous solution from the foam film using a pipette or the like to reduce the film thickness, or to add the aqueous solution to the foam film to increase the film thickness. A typical foam film thickness is 1 μm to 200 μm, more preferably 10 μm to 100 μm. Method for measuring thickness of foam film: The position of the film-air interface was measured by focusing with an optical microscope, and the thickness was measured (device used: nanosearch microscope, model number: OLS3500, manufacturer: Olympus).

  The foam film-forming aqueous solution contains the surfactant compound or the compound in a sol state in which it is not gelled at the stage of the foam film formation process.

  The surfactant that can be added to the aqueous solution for forming a foam film together with a compound containing two or more polymerizable functional groups per molecule is not particularly limited, but for example, a surfactant such as sucrose fatty acid ester can be used. .

  In the aqueous solution for forming a foam film, a polymerization initiator for initiating polymerization between the functional groups is further added as necessary. As polymerization initiators, radical polymerization initiators, anionic polymerization initiators, and cationic polymerization initiators that are activated or reacted by the action of external energy such as actinic radiation and heat to generate active species (radicals, anions or cations) are preferably used. it can. Actinic radiation is preferable as the external energy. As the active radiation, ultraviolet rays, electron beams, gamma rays, and plasma can be used, and ultraviolet rays or electron beams are particularly preferable. Other polymerization initiators, such as radical polymerization initiators that generate radicals by redox reaction, represented by hydrogen peroxide-ferrous salt, bases (anionic polymerization initiators), acids (cationic polymerization initiators), etc. Can also be used, and may be appropriately contained in the aqueous solution for forming a foam film. Specific examples of preferable polymerization initiators include 2-hydroxy-2-methyl-propiophenone (a radical is generated by the action of actinic radiation). The concentration of the polymerization initiator is not particularly limited, but can typically be 0.01 to 1% by weight in the aqueous solution.

  The foam film-forming aqueous solution may contain other components as appropriate. Specifically, the aqueous solution may contain a surfactant, an emulsification aid, a wetting agent, etc. for the purpose of stabilizing the foam film. As the surfactant, a surfactant with high safety to a living body such as sucrose fatty acid ester is preferable. The concentration of the surfactant is not particularly limited, but can typically be 0.01 to 1% by weight in the aqueous solution. As the emulsification aid, emulsification aids with high safety to the living body, such as methylcellulose, glycerin, polyethylene glycol, polyvinyl alcohol, sucrose, and polyglycerin are preferable. The concentration of the emulsification aid is not particularly limited, but can typically be 0.01 to 10% by weight in the aqueous solution. Volatilization of water from the foam film before gelation causes rupture of the foam film. Since the emulsification auxiliary agent has an action of suppressing volatilization of water from the foam film, that is, an action as a wetting agent for the foam film, it can be added for the purpose of suppressing foam film rupture.

  In addition to the action as a wetting agent, the above-mentioned emulsification auxiliary agent such as polyethylene glycol enters between the polymers constituting the hydrogel thin film and the dried gel thin film to suppress the cross-linking between the polymers and increase the flexibility of the film. It also has the effect. For this reason, the hydrogel thin film and dry gel thin film prepared from the aqueous solution for foam film formation containing an emulsification auxiliary agent have the advantageous effect that it is highly flexible and has high adhesiveness to a biological surface such as skin.

  In the foam film-forming aqueous solution, it is possible to further blend desired components to be supplied to the object to be pasted, such as components effective as pharmaceuticals and components effective as cosmetics. The components contained in the foam film-forming aqueous solution can be incorporated and retained in the polymer network structure in the hydrogel thin film and the dried gel thin film.

  It is considered that the surface active substance molecules are arranged on both the front and back surfaces of the foam membrane so that the hydrophobic portion is on the outside and the hydrophilic portion is on the inside. Since the foam film has a homogeneous structure on both sides, the hydrogel thin film and the dried gel thin film prepared from the foam film are homogeneous on the front and back sides and can be used without distinction between the front and back sides.

<Gelification process>
In the gelling step, the hydrogel thin film gelled in a state where the foam film contains water by bonding the functional groups in the foam film by reaction to crosslink between the surface active compound or the molecules of the compound. Is a step of forming.

  In the present invention, the term “hydrogel” refers to a gel in which a large amount of water is held in a network structure formed by the surface-active compounds or the molecules of the compounds bonded to each other. In the gelation step, before the foam film dries, it gels in a state containing water to form a hydrogel. The conditions for the gelation step are not necessarily required so that the moisture of the foam film is completely maintained, and may be any conditions as long as a hydrogel thin film containing water is formed.

  It is a feature of the present invention to form a hydrogel thin film containing water as an object or as an intermediate for producing a dry gel thin film. Patent Document 2 discloses a thin film obtained by crosslinking a surface-active polymer. However, since the thin film obtained in this document is prepared from a once dried film, voids in a network structure formed by forming a gel are disclosed. The part is estimated to be small, and it is considered that the function of retaining moisture and the function of permeating functional components are not sufficient.

  The gelation step is not particularly limited as long as it is a step in which polymerizable functional groups of different molecules of the surfactant compound or the compound are bonded by reaction. In embodiments where the polymerizable functional group is a chain polymerizable functional group, the gelation process is initiated by generating active species (radicals, anions, cations) for chain polymerization in the foam film.

  The following two embodiments can be mentioned as a method for generating an active species for chain polymerization in a foam film.

  In 1st embodiment, the polymerization initiator which produces | generates an active seed | species exists beforehand in the aqueous solution for foam film formation, and an active seed | species is produced in a foam film in a gelatinization process.

  In the second embodiment, external energy is applied to the foam film in the gelation step, and active species are generated in the foam film by the action of the external energy.

  Of these embodiments, the first embodiment is particularly preferred. In the first embodiment, in particular, it is preferable to use a polymerization initiator that generates active species by the action of external energy such as actinic radiation and heat. In that case, the gelation step acts on the foam film with a predetermined external energy. To generate active species from the polymerization initiator. The preferred embodiments of the external energy and the polymerization initiator are as described in detail in the section “Process for forming foam film”.

  The gelation step is preferably performed at a low temperature, for example, 4 to 23 ° C., for a short time, for example, 0.1 to 10 seconds.

  In order to suppress moisture volatilization in the gelation step, it is preferable to perform the gelation step in a closed container adjusted to saturated humidity.

  The thickness of the hydrogel thin film is not particularly limited, but is typically 1 μm to 200 μm, and more preferably 10 μm to 100 μm. When the thickness of the hydrogel thin film is within this range, the flexibility of the film is very high, so that the adhesion to a surface having fine irregularities such as skin is high, and the thin film is not easily peeled off after being attached. Measuring method of thickness of hydrogel thin film: The position of the film-air interface was measured by focusing with an optical microscope, and the thickness was measured (device used: nanosearch microscope, model number: OLS3500, manufacturer: Olympus).

<Drying process>
The dried gel film can be prepared by further drying the hydrogel film.

  The gelation step and the drying step do not need to be performed as separate steps, and the hydrogel thin film is processed as an intermediate product by forming the hydrogel thin film from the foam film and then continuing the drying of the hydrogel thin film. It is also possible to obtain a dry gel thin film without obtaining.

  The conditions for drying are not particularly limited, but are preferably dried at 4 to 30 ° C. for 2 hours or more. The moisture in the dried gel thin film is not particularly limited, but is preferably dried until the moisture content is 10% by weight or less.

  Although the thickness of a dry gel thin film is not specifically limited, Typically, it is 100 nm-100 micrometers, and it is more preferable that it is 500 nm-10 micrometers. When the thickness of the dried gel thin film is within this range, the film is very flexible, and therefore, the adhesion to a surface having fine irregularities such as skin is high, and the thin film is not easily peeled off after being applied. In addition, when the thickness is equal to or greater than the above lower limit value, the structural color due to light interference can be visually observed, so that the dried gel thin film can be visually identified without being colored by a colorant despite being extremely thin. is there. Method for measuring the thickness of the dried gel thin film: The position of the film-air interface was measured by focusing with an optical microscope, and the thickness was measured (device used: nanosearch microscope, model number: OLS3500, manufacturer: Olympus).

<Sheets for sticking sheets>
The hydrogel thin film or the dried gel thin film of the present invention is suitable for use in at least a part to be stuck to a sticking object in a sheet-like sticking article.

  The sheet-like pasting article may be a sheet-like article having a multilayer structure in which one or more other layers are laminated on the hydrogel thin film or the dried gel thin film, or another layer on the hydrogel thin film or the dried gel thin film. It may be a sheet-like article having a single layer structure in which is not laminated. FIG. 5 shows a sheet-like application article 50 having a multilayer structure in which the hydrogel thin film 22 and another layer 51 are laminated. FIG. 6 shows a sheet-like pasting article 60 having a multilayer structure in which the dried gel thin film 23 and another layer 61 are laminated.

  The hydrogel thin film and the dry gel thin film have high adsorptivity on the surface of a living body or a biomaterial such as skin, and have high flexibility. For this reason, the sheet-like sticking article having the hydrogel thin film and the dry gel thin film is hardly peeled even when it is stuck on a fine uneven surface that moves like skin. In FIG. 3, when a sheet-like application article 30 having a single layer structure of the hydrogel thin film 22 is applied to the skin surface of the joint portion of the finger in a bent state (upper figure), the finger is stretched after application. It is schematically shown that even if wrinkles are formed on the skin surface, the hydrogel thin film 22 is also deformed following the shape of the wrinkles (below), and it is difficult to peel even if the fingers are repeatedly bent and stretched. FIG. 4 schematically shows that the same effect is obtained even when the sheet-like article 40 for pasting having a single-layer structure of the hydrogel thin film 23 is used.

  Since the hydrogel thin film or the dry gel thin film has a network structure of a polymer compound, a desired component to be supplied to an object to be pasted, such as a component effective as a medicine or a component effective as a cosmetic, is included. It can be retained and / or transmitted.

  As a first method for retaining a desired component in a hydrogel thin film or a dry gel thin film, there is a method of preparing a hydrogel thin film or a dry gel thin film using a foam film-forming aqueous solution further added with a desired component. Can be mentioned. As a second method for retaining a desired component in the hydrogel thin film or dry gel thin film, a method of bringing the desired component into contact with the prepared hydrogel thin film or dry gel thin film can be mentioned. The contact of the desired component in the second method may be any method such as immersing the hydrogel thin film or dry gel thin film in a liquid containing the component, or applying the liquid containing the component to the hydrogel thin film or dry gel thin film. Can be performed.

  As shown in FIGS. 5 and 6, in the embodiment in which the hydrogel thin film 22 or the dried gel thin film 23 is laminated with the other layers 51 and 61, the other layers 51 and 61 have a desired structure to be supplied to the object to be adhered. It can be a layer containing components. In this embodiment, the desired component can be supplied to the object through the hydrogel thin film 22 or the dried gel thin film 23. The other layers 51, 61 can be structured to contain the desired components in a suitable support carrier. It is not essential that the other layers 51 and 61 and the hydrogel thin film 22 or the dried gel thin film 23 are directly laminated, and other other layers may be interposed therebetween.

  The hydrogel thin film or the dried gel thin film can also be used for the purpose of protecting the surface of the living body or the biomaterial.

  The sheet-like article for sticking provided with the hydrogel thin film or the dried gel thin film of the present invention is useful in cosmetic use or medical use. Specifically, a cosmetic pack material, a wound dressing material for protecting wounds on the skin surface, a percutaneous absorption preparation for applying a drug transdermally, and affixed to the surface of an in vivo organ or tissue, It can be used in applications such as a protective sheet that protects the surface of an organ or tissue and / or prevents adhesion with another organ or tissue.

<Sheet-like pasting article with support frame>
The sheet-like article for sticking of the present invention is preferably one in which the shape is held by a support frame. The hydrogel thin film or the dried gel thin film is preferably fixed in a state of being stretched on the support frame so as to close the opening of the support frame.

  The support frame is preferably a frame used when forming the foam film. As shown in FIG. 1, the frame 10 used when forming the foam film can be used as a support frame without being separated from the film even after the preparation of the hydrogel thin film 22 or the dry gel thin film 23. In this embodiment, the periphery of the hydrogel thin film 22 or the dry gel thin film 23 is bonded to the support frame 10. In the embodiment using the frame used for forming the foam film as the support frames 71 and 81, one or more other layers may be further laminated on the hydrogel thin film 22 or the dried gel thin film 23 (FIGS. 7 and 8). reference).

  In another embodiment, the hydrogel thin film or the dried gel thin film is separated from the frame used when forming the foam film, and fixed to a separately prepared support frame having one or more openings so as to close the openings. You can also. Also in this embodiment, at any stage, the hydrogel thin film or the dried gel thin film is subjected to treatments such as cutting to an appropriate size, addition of desired components, and lamination with other layers as necessary. Can do.

  The support frame is preferably a flexible film member. As shown in FIG. 9, the surface 90 of the sheet-like application article 90 including the support frame 91 formed of a film-like member and the hydrogel thin film 22 stretched so as to close the opening of the support frame 91 is not flat. The surface of the hydrogel thin film 22 that can be deformed along the surface shape of the object 92 and is sufficiently fixed to the support frame 91 can be sufficiently adsorbed to the surface of the object 92 (see FIG. 9b). The peripheral edge of the hydrogel thin film 22 and the support frame 91 are weakly coupled to such an extent that they are separated when the support frame 91 is peeled off after the surface of the hydrogel thin film 22 and the surface of the object 92 are adsorbed. Can be left on the surface of the adherend 92 (FIG. 9c). As shown in FIG. 10, a sheet-like sticking article 100 including a support frame 101 formed of a film-like member and a dry gel thin film 23 stretched so as to close the opening of the support frame 101 is also covered by a similar operation. It can be affixed to the surface of the patch 92. 7 and 8, a sheet with a support frame in which support frames 71 and 81 at the periphery of the hydrogel thin film 22 or the dried gel thin film 23 multilayered together with other layers 51 and 61 are formed of a flexible film-like member. The same sticking is also possible for the shaped sticking articles 70 and 80.

<Experiment 1>
<Creating a sticker sheet>
A. Preparation of Support Frame A polystyrene film (manufactured by SUNDIC) having a size of 4 cm × 4 cm and a thickness of 250 μm was cut out so that a 3.2 cmφ true circular opening was formed at the center to prepare a support frame having an opening.

B. Preparation of Solution In pure water, 50% by mass of polyethylene glycol diacrylate (manufactured by Sigma Aldrich), 1% by mass of 2-hydroxy-2-methyl-propiophenone (manufactured by Sigma Aldrich), sucrose fatty acid ester ( A solution prepared by dissolving 0.1% by weight of Mitsubishi Chemical Foods Co., Ltd. was used as an aqueous solution for forming a foam film.

C. Preparation of hydrogel thin film from foam film A hydrogel thin film was prepared as follows.
The support frame is immersed in the foam film-forming aqueous solution for 1 second, and then the support film is removed from the foam film-forming aqueous solution so that the support frame is parallel to the vertical direction. It was pulled up so that a foam film was formed. After pulling, the hydrogel thin film having a thickness of about 10 μm was formed by rapidly irradiating the foam film with ultraviolet rays having a wavelength of 250 to 400 nm at a dose of 30 mJ / cm ² (measured at a wavelength of 350 nm) to cause gelation.

The aqueous solution for forming a foam film in a sol state is coated on a glass substrate so as to have a thickness of 1 mm, and a hydrogel film is produced by irradiating with ultraviolet rays having a wavelength of 250 to 400 nm at a dose of 30 mJ / cm ² to be gelled. A comparative sample was used. Since the comparative sample has strength, it can be peeled off from the substrate with tweezers and handled.

<Paste evaluation>
When the hydrogel thin film is formed in the opening created as described above, the hydrogel thin film adheres to the skin by surface tension when the hydrogel thin film is brought into contact with the human skin by grasping the support frame, and the support frame is removed from the skin. When moved away, the hydrogel thin film separated from the support frame portion, and only the hydrogel thin film could be applied to the skin (FIG. 9). The hydrogel thin film is very thin and can be applied to curved or refracted parts. When applied to a bent finger joint, all of the hydrogel thin film adheres to the skin so that it follows the curved shape. Even during refraction, the hydrogel thin film did not peel off while being in close contact with the skin, and the appearance after application was hardly noticeable.

  On the other hand, when the comparative sample (1 mm thick hydrogel thin film) is brought into contact with the bent finger joint, a part of it floats, and the adhesion of the hydrogel thin film deviates from the skin when the finger is refracted. The appearance was also conspicuous.

<Experiment 2>
F. A support frame in which a hydrogel thin film was formed in an opening was prepared in the same manner as in Experiment 1 for creating a dry gel film . Each hydrogel thin film fixed to the support was subjected to a drying treatment at 4 ° C. for 120 minutes to obtain a dried film (dry gel thin film) having a thickness of about 5 μm.

Claims (6)

A bubble film of an aqueous solution containing a surface active compound containing two or more polymerizable functional groups per molecule, or an aqueous solution bubble film containing a compound containing two or more polymerizable functional groups per molecule and a surfactant A foam film forming step to be formed in the opening;
Gelation that forms a hydrogel thin film in which the foam film contains water by cross-linking the surface active compound or molecules of the compound by bonding the functional groups in the foam film by reaction. Process,
A method for producing a hydrogel thin film. A bubble film of an aqueous solution containing a surface active compound containing two or more polymerizable functional groups per molecule, or an aqueous solution bubble film containing a compound containing two or more polymerizable functional groups per molecule and a surfactant A foam film forming step to be formed in the opening;
Gelation that forms a hydrogel thin film in which the foam film contains water by cross-linking the surface active compound or molecules of the compound by bonding the functional groups in the foam film by reaction. Process,
And a drying step of drying the hydrogel thin film. The functional group is a chain polymerizable functional group,
The gelation step includes generating an active species for initiating chain polymerization in the foam film and proceeding with a binding reaction of the functional group.
The method of claim 1. The functional group is a chain polymerizable functional group,
The gelation step includes generating an active species for initiating chain polymerization in the foam film and proceeding with a binding reaction of the functional group.
The method of claim 2. A hydrogel thin film having adhesiveness to a living body or a biomaterial,
A polymer network formed by intermolecular crosslinking of compounds containing two or more chain-polymerizable functional groups per molecule;
The said thin film whose front and back are homogeneous and whose thickness is 10-100 micrometers. A dry gel thin film having adhesiveness to a living body or a biomaterial,
A polymer network formed by intermolecular crosslinking of compounds containing two or more chain-polymerizable functional groups per molecule;
The said thin film whose front and back are homogeneous, a moisture content is 10 weight% or less, and thickness is 500 nm-10 micrometers.

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