Painkiller and its manufacturing method

Abstract

To provide an analgesic that can quickly reduce a pain caused by skin or mucosa injury.SOLUTION: An analgesic includes a polymer (A) having a structural unit derived from an ethylenic unsaturated monomer having a carboxyl group, and a polymer (B) having a structural unit derived from an ethylenic unsaturated monomer having a functional group capable of forming a hydrogen bond with a carboxyl group (excluding the polymer (A)). It forms a hydrogel upon contact with water.SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to a pain-relieving material and a method for producing the same, and more particularly to a pain-relieving material that forms a hydrogel upon contact with water and a method for producing the same. [Background technology]

[0002] Stomatitis is an inflammation of the oral mucosa, and refers to symptoms such as erosion, erythema, and ulcers that develop on the oral mucosa, corners of the mouth, and lips. When stomatitis becomes severe, it can cause not only discomfort but also pain and bleeding, making it difficult to eat, drink, or speak. Therefore, various therapeutic agents containing medicinal ingredients have been developed as therapeutic agents for stomatitis (see, for example, Patent Documents 1 and 2).

[0003] Patent Document 1 proposes a preventive or therapeutic agent for oral mucosal diseases containing sofalcone as an active ingredient, and Patent Document 2 proposes a composition for oral mucosal use containing triamcinolone acetonide and cetylpyridinium chloride. [Prior art documents] [Patent documents]

[0004] [Patent Document 1] Japanese Patent Application Laid-Open No. 2009-126813 [Patent Document 2] Japanese Patent Application Laid-Open No. 2017-206486 Summary of the Invention [Problem to be solved by the invention]

[0005] While therapeutic agents containing medicinal ingredients, such as those described in Patent Documents 1 and 2, are effective in healing stomatitis, there is a concern that they may not be able to sufficiently relieve the pain associated with stomatitis until the healing effect of the medicinal ingredients is fully achieved. On the other hand, it is important for patients to be able to quickly relieve the pain associated with stomatitis and be able to eat, drink, speak, and so on without any problems. Similarly, when the skin or mucous membrane is damaged by burns, trauma, or the like, it is necessary to protect the affected area from irritation and relieve pain as quickly as possible.

[0006] The present invention has been made in view of the above circumstances, and an object of the present invention is to provide an analgesic material that can quickly relieve pain associated with damage to the skin or mucous membranes. [Means for solving the problem]

[0007] The present inventors conducted extensive research to solve the above problems and discovered that by using a hydrogel-forming material containing a specific polymer component that forms a hydrogel through hydrogen bonding, it is possible to firmly adhere to biological tissue and cover the affected area, thereby achieving an excellent analgesic effect, and thus completed the present invention. Specifically, the present invention provides the following means.

[0008] [1] A pain-relieving material comprising a polymer (A) having a structural unit derived from an ethylenically unsaturated monomer having a carboxyl group, and a polymer (B) (excluding the polymer (A)) having a structural unit derived from an ethylenically unsaturated monomer having a functional group capable of forming a hydrogen bond with a carboxyl group, and which forms a hydrogel upon contact with water.

[0009] [2] The analgesic material according to the above [1], wherein the polymer (A) is a crosslinked polymer. [3] The analgesic material according to the above [1] or [2], wherein the polymer (A) is poly(meth)acrylic acid. [4] The analgesic material according to any one of the above [1] to [3], wherein the polymer (B) has an amide group. [5] The analgesic material according to any one of the above [1] to [4], wherein the polymer (B) is at least one selected from the group consisting of polyvinylpyrrolidone and poly(meth)acrylamide. [6] A pain-relieving material according to any one of [1] to [5] above, which is used for stomatitis, burns, or trauma.

[0010] [7] A method for producing a pain-relieving material, the pain-relieving material forming a hydrogel upon contact with water, comprising the steps of: obtaining a film-like solid material containing one of polymer (A) having a structural unit derived from an ethylenically unsaturated monomer having a carboxyl group, and polymer (B) having a structural unit derived from an ethylenically unsaturated monomer having a functional group capable of forming a hydrogen bond with a carboxyl group (excluding polymer (A)); and bringing the film-like solid material into contact with a polymer solution containing the other of polymer (A) and polymer (B), followed by drying. [Effects of the Invention]

[0011] According to the present invention, a hydrogel-forming material obtained from a polymer (A) having a structural unit derived from an ethylenically unsaturated monomer having a carboxyl group and a polymer (B) having a structural unit derived from an ethylenically unsaturated monomer having a functional group capable of forming a hydrogen bond with a carboxyl group is brought into contact with an injured site of the skin, mucous membrane, or the like, and the injured site is covered with the hydrogel-forming material, thereby enabling rapid relief of pain associated with the injury. DETAILED DESCRIPTION OF THE INVENTION

[0012] The present invention will be described in detail below. In this specification, "(meth)acrylic" means acrylic and / or methacrylic, and "(meth)acrylate" means acrylate and / or methacrylate.

[0013] 《Analgesic material》 The analgesic material of the present invention (hereinafter also referred to as "the analgesic material") is a hydrogel-forming material that forms a hydrogel upon contact with water. When placed on wet biological tissue, the hydrogel-forming material rapidly absorbs bodily fluids such as saliva, tissue fluid, and blood, swells, and firmly adheres to the biological tissue. This allows the analgesic material to continuously cover the affected area even in areas where it is prone to coming off after being applied to the biological tissue, and it exhibits an analgesic effect against damage to the skin or mucous membrane.

[0014] This analgesic material comprises a polymer (A) having a structural unit derived from an ethylenically unsaturated monomer having a carboxyl group, and a polymer (B) (excluding polymer (A)) having a structural unit derived from an ethylenically unsaturated monomer having a functional group capable of forming a hydrogen bond with a carboxyl group (hereinafter also referred to as "functional group E"). This analgesic material has a crosslinked structure formed by hydrogen bonding between the carboxyl group in polymer (A) and functional group E in polymer (B), thereby exhibiting water absorption properties. This analgesic material will be described in detail below.

[0015] <Polymer (A)> As the polymer (A), a polymer mainly composed of structural units derived from an ethylenically unsaturated monomer having a carboxyl group (hereinafter also referred to as "unsaturated monomer (ma)") can be preferably used. Specific examples of the unsaturated monomer (ma) include (meth)acrylic acid, itaconic acid, crotonic acid, maleic acid, fumaric acid, citraconic acid, cinnamic acid, succinic acid monohydroxyethyl (meth)acrylate, ω-carboxy-caprolactone mono(meth)acrylate, β-carboxyethyl (meth)acrylate, and 4-carboxystyrene. Among the unsaturated monomers (ma), (meth)acrylic acid is particularly preferred because it can enhance adhesiveness to biological tissues.

[0016] In the polymer (A), the content of structural units derived from the unsaturated monomer (ma) is preferably 40% by mass or more, more preferably 50% by mass or more, even more preferably 60% by mass or more, even more preferably 70% by mass or more, even more preferably 80% by mass or more, and even more preferably 90% by mass or more, based on the total structural units constituting the polymer (A). When the structural units derived from the unsaturated monomer (ma) in the polymer (A) are in the above range, it is preferable in that a hydrogel having higher adhesiveness to biological tissue can be obtained. The unsaturated monomer (ma) constituting the polymer (A) may be of one type or two or more types.

[0017] In view of excellent adhesiveness to biological tissues, the polymer (A) is particularly preferably poly(meth)acrylic acid. When the polymer (A) is poly(meth)acrylic acid, the polymer (A) preferably contains 70% by mass or more of (meth)acrylic acid units, more preferably 80% by mass or more, even more preferably 90% by mass or more, and even more preferably 95% by mass or more.

[0018] The method for obtaining the polymer (A) is not limited to the method using the unsaturated monomer (ma). For example, the polymer (A) may be obtained by polymerizing a (meth)acrylic acid ester monomer and then hydrolyzing the polymer. Alternatively, the polymer (A) may be obtained by polymerizing a nitrogen-containing monomer such as (meth)acrylamide or (meth)acrylonitrile and then treating the polymer with a strong alkali, or by reacting a polymer having a hydroxyl group with an acid anhydride.

[0019] As the polymer (A), at least one of a crosslinked polymer and a polymer having a weight-average molecular weight of 1,800,000 or more (hereinafter also referred to as a "high molecular weight polymer (AH)") can be preferably used. Among these, the polymer (A) is particularly preferably a crosslinked polymer because of its superior swelling property in contact with water and adhesive property to biological tissues.

[0020] The method for producing the crosslinked polymer is not particularly limited, and examples of the method for producing the crosslinked polymer include the following methods (1) and (2). (1) A method of copolymerizing an ethylenically unsaturated monomer having a crosslinkable functional group (hereinafter also referred to as "unsaturated monomer (mc)") with an unsaturated monomer (ma) (2) A method in which a polymer having a reactive functional group is synthesized and crosslinked by adding a crosslinking agent as needed. Of these, method (1) is preferred because the procedure is simple and the degree of crosslinking can be easily controlled.

[0021] Examples of the unsaturated monomer (mc) include polyfunctional polymerizable monomers having two or more polymerizable unsaturated groups, and self-crosslinking monomers having a crosslinkable functional group capable of self-crosslinking (e.g., a hydrolyzable silyl group). Specific examples of polyfunctional polymerizable monomers include polyfunctional (meth)acrylate compounds, polyfunctional alkenyl compounds, and compounds having both a (meth)acryloyl group and an alkenyl group. Of these, polyfunctional alkenyl compounds are preferred as ethylenically unsaturated monomers having a crosslinkable functional group, since they are more likely to produce a uniform crosslinked structure.

[0022] Specific examples of polyfunctional alkenyl compounds include polyfunctional allyl ether compounds such as trimethylolpropane diallyl ether, trimethylolpropane triallyl ether, pentaerythritol diallyl ether, pentaerythritol triallyl ether, tetraallyloxyethane, and polyallylsucrose; polyfunctional allyl compounds such as diallyl phthalate; polyfunctional vinyl compounds such as divinylbenzene; and alkenyl group-containing (meth)acrylic acid compounds such as allyl (meth)acrylate, isopropenyl (meth)acrylate, butenyl (meth)acrylate, pentenyl (meth)acrylate, and 2-(2-vinyloxyethoxy)ethyl (meth)acrylate. Among these polyfunctional alkenyl compounds, polyfunctional allyl ether compounds having multiple allyl ether groups in the molecule are particularly preferred.

[0023] Specific examples of the self-crosslinking monomer include hydrolyzable silyl group-containing vinyl monomers, etc. Examples of the hydrolyzable silyl group-containing vinyl monomers include vinyl silanes such as vinyltrimethoxysilane, vinyltriethoxysilane, vinylmethyldimethoxysilane, and vinyldimethylmethoxysilane; silyl group-containing (meth)acrylic acid esters such as trimethoxysilylpropyl (meth)acrylate, triethoxysilylpropyl (meth)acrylate, and methyldimethoxysilylpropyl (meth)acrylate; trimethoxysilylpropyl vinyl ether; and vinyl trimethoxysilylundecanoate.

[0024] When the polymer (A) contains the structural unit (mc), the amount of the structural unit (mc) contained in the polymer (A) is preferably 0.01% by mass or more, more preferably 0.1% by mass or more, based on all structural units constituting the polymer (A). The amount of the structural unit (mc) contained in the polymer (A) is preferably 5% by mass or less, more preferably 2% by mass or less, and even more preferably 1% by mass or less, based on all structural units constituting the polymer (A). The structural unit (mc) contained in the polymer (A) may be of one type or two or more types.

[0025] The polymer (A) may further have structural units derived from monomers other than the unsaturated monomers (ma) and (mc) (hereinafter also referred to as "other monomers (md)"), provided that the effects of the present invention are not impaired. Examples of other monomers (md) include (meth)acrylic acid alkyl esters, aliphatic cyclic (meth)acrylic acid esters, aromatic (meth)acrylic acid esters, (meth)acrylic acid alkoxyalkyl esters, (meth)acrylic acid hydroxyalkyl esters, and polyalkylene glycol mono(meth)acrylates.

[0026] Specific examples of these include (meth)acrylic acid alkyl esters such as methyl (meth)acrylate, ethyl (meth)acrylate, isopropyl (meth)acrylate, n-propyl (meth)acrylate, n-butyl (meth)acrylate, isobutyl (meth)acrylate, tert-butyl (meth)acrylate, hexyl (meth)acrylate, and 2-ethylhexyl (meth)acrylate.

[0027] Specific examples of the aliphatic cyclic esters of (meth)acrylic acid include cyclohexyl (meth)acrylate, methylcyclohexyl (meth)acrylate, tert-butylcyclohexyl (meth)acrylate, cyclododecyl (meth)acrylate, isobornyl (meth)acrylate, adamantyl (meth)acrylate, dicyclopentenyl (meth)acrylate, and dicyclopentanyl (meth)acrylate, etc. Specific examples of the aromatic esters of (meth)acrylic acid include phenyl (meth)acrylate, benzyl (meth)acrylate, phenoxymethyl (meth)acrylate, 2-phenoxyethyl (meth)acrylate, and 3-phenoxypropyl (meth)acrylate, etc.

[0028] Specific examples of (meth)acrylic acid alkoxyalkyl esters include methoxymethyl (meth)acrylate, methoxyethyl (meth)acrylate, ethoxyethyl (meth)acrylate, n-propoxyethyl (meth)acrylate, n-butoxyethyl (meth)acrylate, methoxypropyl (meth)acrylate, ethoxypropyl (meth)acrylate, n-propoxypropyl (meth)acrylate, n-butoxypropyl (meth)acrylate, methoxybutyl (meth)acrylate, ethoxybutyl (meth)acrylate, n-propoxybutyl (meth)acrylate, and n-butoxybutyl (meth)acrylate.

[0029] Specific examples of the (meth)acrylic acid hydroxyalkyl ester include 2-hydroxyethyl (meth)acrylate, 2-hydroxypropyl (meth)acrylate, 3-hydroxypropyl (meth)acrylate, 2-hydroxybutyl (meth)acrylate, 3-hydroxybutyl (meth)acrylate, and 4-hydroxybutyl (meth)acrylate, etc. Examples of the polyalkylene glycol mono(meth)acrylate include polyethylene glycol mono(meth)acrylate, polypropylene glycol mono(meth)acrylate, and polyethylene glycol-polypropylene glycol mono(meth)acrylate, etc.

[0030] In the polymer (A), the content of structural units derived from other monomers (md) is preferably 5% by mass or less, more preferably 2% by mass or less, and even more preferably 1% by mass or less, based on the total structural units constituting the polymer (A). The other monomers constituting the polymer (A) may be one type or two or more types.

[0031] When a crosslinked polymer is used as the polymer (A), commercially available crosslinked polymers can also be used, such as Junron (registered trademark) PW-120, Junron PW-121, and Junron PW-312S (all manufactured by Toagosei Co., Ltd.), Carbopol 934P NF, Carbopol 981, Carbopol Ultrez 10, and Carbopol Ultrez 30 (all manufactured by Lubrizol).

[0032] When a high molecular weight polymer (AH) is used as the polymer (A), the weight average molecular weight (Mw) of the high molecular weight polymer (AH) is preferably 1.8 million or more from the viewpoint of sufficiently increasing adhesiveness to biological tissue. Furthermore, from the viewpoint of ease of handling, the Mw of the high molecular weight polymer (AH) is preferably 50 million or less, more preferably 30 million or less, and even more preferably 10 million or less. The molecular weight of the high molecular weight polymer (AH) is a polystyrene-equivalent value measured by gel permeation chromatography (GPC) using a tetrahydrofuran eluent after methylating the carboxyl groups with trimethylsilyldiazomethane.

[0033] <Polymer (B)> Polymer (B) is not particularly limited as long as it has a structural unit derived from an ethylenically unsaturated monomer having a functional group E capable of forming a hydrogen bond with a carboxyl group in polymer (A) (hereinafter also referred to as "unsaturated monomer (mb)") and is a polymer different from polymer (A). Examples of functional group E include an amide group, a cyano group, a carbonyl group, an amino group, and a hydroxyl group. Polymer (B) may have one type of functional group E, or two or more types of functional groups E.

[0034] Among these, the functional group E is preferably an amide group and / or a hydroxyl group, and particularly preferably an amide group, because a hydrogel-forming material with excellent water swelling properties can be obtained by forming a hydrogen bond between the carboxyl group of the polymer (A) and the functional group E.

[0035] The polymer (B) having an amide group can be produced, for example, by polymerizing an ethylenically unsaturated monomer having an amide group. Examples of the ethylenically unsaturated monomer having an amide group include (meth)acrylamide, N,N-dimethyl(meth)acrylamide, N,N-dimethylaminopropyl(meth)acrylamide, N-methyl(meth)acrylamide, N-vinyl-2-pyrrolidone, and 1-vinyl-4-methyl-2-pyrrolidone.

[0036] In the polymer (B), the content of structural units derived from the unsaturated monomer (mb) is preferably 70% by mass or more, more preferably 80% by mass or more, even more preferably 90% by mass or more, and even more preferably 97% by mass or more, based on all structural units constituting the polymer (B).

[0037] As the polymer (B), at least one of a crosslinked polymer and a polymer having a weight-average molecular weight of 10,000 or more (hereinafter also referred to as a "high molecular weight polymer (BH)") can be preferably used, with the high molecular weight polymer (BH) being more preferably used. Furthermore, from the viewpoint of obtaining a sponge that forms a highly swellable hydrogel upon contact with water, the polymer (B) is preferably at least one of polyvinylpyrrolidone and poly(meth)acrylamide. Among these, at least one of polyvinylpyrrolidone and polyacrylamide is more preferred, in terms of excellent polymerizability of the constituent monomers and ease of production of the polymer (B).

[0038] Polyvinylpyrrolidone is typically a polymer made of N-vinyl-2-pyrrolidone. However, it may contain structural units derived from a monomer other than N-vinyl-2-pyrrolidone, provided that the effects of the present invention are not impaired. Specific examples of monomers other than N-vinyl-2-pyrrolidone include the compounds exemplified as other monomers that may constitute polymer (A). In polyvinylpyrrolidone, the content of structural units derived from monomers other than N-vinyl-2-pyrrolidone is preferably 3% by mass or less, more preferably 1% by mass or less, and even more preferably 0.5% by mass or less, based on the total structural units constituting polyvinylpyrrolidone.

[0039] Similarly, polyacrylamide is typically a polymer made of acrylamide. However, it may contain structural units derived from monomers other than acrylamide, provided that the effects of the present invention are not impaired. Specific examples of monomers other than acrylamide include the compounds exemplified as other monomers that may constitute polymer (A). In polyacrylamide, the content of structural units derived from monomers other than acrylamide is preferably 3% by mass or less, more preferably 1% by mass or less, and even more preferably 0.5% by mass or less, based on the total structural units constituting polyacrylamide.

[0040] Polymethacrylamide is typically a polymer made of methacrylamide. However, it may contain structural units derived from a monomer other than methacrylamide, provided that the effects of the present invention are not impaired. Specific examples of monomers other than methacrylamide include the compounds exemplified as other monomers that may constitute polymer (A). In polymethacrylamide, the content of structural units derived from monomers other than methacrylamide is preferably 3% by mass or less, more preferably 1% by mass or less, and even more preferably 0.5% by mass or less, based on the total structural units constituting the polymethacrylamide.

[0041] When a high molecular weight polymer (BH) is used as the polymer (B), the weight average molecular weight (Mw) of the high molecular weight polymer (BH) is not particularly limited, but from the viewpoint of ensuring mechanical strength and thickening effect, it is preferably 10,000 or more, more preferably 30,000 or more, and even more preferably 50,000 or more. From the viewpoint of handleability, the Mw of the high molecular weight polymer (BH) is preferably 100 million or less, more preferably 50 million or less, and even more preferably 30 million or less. The molecular weight of the polymer (B) is a polystyrene-equivalent value measured by GPC.

[0042] The total amount of polymer (A) and polymer (B) contained in this analgesic material is preferably 70% by mass or more, more preferably 80% by mass or more, even more preferably 90% by mass or more, and even more preferably 95% by mass or more, of the total amount of this analgesic material, from the viewpoint of obtaining a hydrogel that has high mechanical strength and excellent adhesiveness to biological tissues upon contact with water.

[0043] In the present analgesic material, the contents of polymer (A) and polymer (B) are preferably adjusted so that the amount of polymer (B) is 20 to 500 parts by mass per 100 parts by mass of polymer (A). When the contents of polymer (A) and polymer (B) are within the above ranges, the effect of improving mechanical strength is high, and it is preferable that a hydrogel that exhibits excellent adhesiveness to biological tissue can be formed. From this perspective, the contents of polymer (A) and polymer (B) are more preferably adjusted so that the amount of polymer (B) is 30 to 400 parts by mass, and even more preferably 50 to 300 parts by mass, per 100 parts by mass of polymer (A).

[0044] The polymerization method for producing the polymer (A) and the polymer (B) is not particularly limited. The polymer (A) and the polymer (B) can be obtained by polymerizing the monomers using a known radical polymerization method such as solution polymerization, suspension polymerization, emulsion polymerization, or bulk polymerization. In the case of the solution polymerization method, for example, an organic solvent and the monomers are charged into a reactor, a polymerization initiator (e.g., an azo compound) is added, and the mixture is heated to 40 to 250°C to polymerize, thereby obtaining the target polymer.

[0045] <Other ingredients> The analgesic material may further contain components other than polymer (A) and polymer (B) (hereinafter also referred to as "other components") depending on the purpose of use, etc. Examples of other components include various additives such as anti-inflammatory agents, vitamins, herbal medicines, antioxidants, flavorings, and fragrances, as well as a water-soluble polymer (C) other than polymer (A) and polymer (B). One or more types of other components may be contained. The content of the other components may be appropriately selected depending on each component, as long as the effects of the present invention are not impaired.

[0046] The water-soluble polymer (C) may be a water-soluble polymer that can be commonly used as a thickener, specifically a polysaccharide. Examples of polysaccharides include cellulose derivatives such as hydroxyethyl cellulose, carboxymethyl cellulose, and hydroxypropyl methyl cellulose; mucopolysaccharides such as hyaluronic acid and chondroitin sulfate; water-soluble natural polymeric polysaccharides such as carrageenan, pectin, locust bean gum, guar gum, xanthan gum, and welan gum, as well as salts thereof (e.g., sodium salts). Among these, hyaluronic acid or its salts are preferred as the water-soluble polymer (C). The number-average molecular weight of the water-soluble polymer (C) is, for example, 200,000 or more. The molecular weight of the water-soluble polymer (C) is a polystyrene-equivalent value measured by GPC.

[0047] When the analgesic material contains a water-soluble polymer (C), the content of the water-soluble polymer (C) is preferably 0.01 to 50 parts by mass per 100 parts by mass of the total amount of polymer (A) and polymer (B). By setting the content of the water-soluble polymer (C) within the above range, it is possible to improve the water retention of the hydrogel. From this viewpoint, the content of the water-soluble polymer (C) is more preferably 0.1 parts by mass or more, and even more preferably 0.5 parts by mass or more, per 100 parts by mass of the total amount of polymer (A) and polymer (B). Furthermore, the upper limit of the content of the water-soluble polymer (C) is more preferably 20 parts by mass or less, and even more preferably 15 parts by mass or less, per 100 parts by mass of the total amount of polymer (A) and polymer (B). As the water-soluble polymer (C), one type may be used alone, or two or more types may be used in combination.

[0048] <Manufacturing method of painkillers> Although there are no particular limitations on the method for producing the analgesic material, it is preferable to use the following method [1] or method [2]. Method [1]: A method in which a film-like solid containing one of the polymers (A) and (B) is brought into contact with a solution containing the other polymer, and then dried. Method [2]: A method of mixing a solution containing polymer (A) and a solution containing polymer (B) in the presence of water-soluble polymer (C) and drying the mixture.

[0049] Here, if an aqueous solution of polymer (A) and an aqueous solution of polymer (B) are simply mixed, a hydrogel is formed very quickly due to hydrogen bonding between the carboxyl group of polymer (A) and the functional group E of polymer (B). However, the dried product of the hydrogel obtained in this manner has insufficient solubility and swelling in water and poor adhesion to biological tissue. In contrast, the above-mentioned methods [1] and [2] can produce hydrogel-forming materials that exhibit excellent water solubility and swelling in water, as well as excellent adhesion to biological tissue. Of these, method [1] is particularly preferred.

[0050] (Regarding Method 1) In method [1], first, a film-like solid material containing one of polymer (A) and polymer (B) (hereinafter also referred to as "first polymer") is prepared. Methods for preparing the film-like solid material include, for example, solution drying and heat pressing. Among these, solution drying is preferred because it can suppress the generation of bubbles and produce a smooth film. When producing a film-like solid material by solution drying, it is preferable to prepare a polymer solution (hereinafter also referred to as "first polymer solution") by dissolving the first polymer in a solvent, and then coat the first polymer solution on a support and dry it. The first polymer constituting the film-like solid material may be polymer (A) or polymer (B).

[0051] Examples of the solvent for dissolving the first polymer include water, a mixture of a water-soluble organic solvent and water, and an organic solvent that is soluble in water. Examples of the organic solvent that is soluble in water include methanol, ethanol, and acetone. Of these, the solvent for dissolving the first polymer is preferably water, ethanol, or a mixture of water and ethanol. The polymer concentration in the first polymer solution is not particularly limited, but is, for example, 0.01 to 10% by mass, and preferably 0.1 to 5% by mass.

[0052] The method for forming a film-like solid on a support is not particularly limited, and known film-forming methods can be used. For example, a film-like solid containing the first polymer can be formed on a support by applying a first polymer solution to the support and preferably heating it to remove the solvent. When heat treatment is performed, the heating temperature is, for example, 50 to 120°C, and the heating time is, for example, 0.1 to 5 hours. The heat treatment may be performed under reduced pressure or under airflow. The thickness of the film-like solid formed on the support is, for example, 1 to 5,000 μm. The moisture content of the film-like solid is, for example, 10% by mass or less.

[0053] Subsequently, the film-like solid formed on the support is brought into contact with a polymer solution (hereinafter also referred to as the "second polymer solution") obtained by dissolving a polymer (A) and a polymer (B) different from the first polymer (hereinafter also referred to as the "second polymer") in a solvent. Examples of the solvent for dissolving the second polymer include the same solvents as those exemplified as the solvent for dissolving the first polymer. Of these, water is particularly preferred from the viewpoint of efficiently carrying out the drying step. The polymer concentration in the second polymer solution is, for example, 0.1 to 30% by mass, and preferably 1 to 20% by mass.

[0054] The method for contacting the film-like solid material containing the first polymer with the second polymer solution is not particularly limited. Examples of methods for contacting the film-like solid material with the polymer solution include applying, dripping, or spraying the second polymer solution onto the surface of the film-like solid material, and immersing the film-like solid material in the second polymer solution. In a preferred embodiment, the second polymer solution is dripped onto the surface of the film-like solid material to form a liquid layer of the second polymer solution on the film-like solid material, and the solid material is then allowed to stand for a predetermined period of time (e.g., 10 to 180 minutes). The thickness of the liquid layer is not particularly limited, but is, for example, 0.1 to 50,000 μm. This allows the first polymer in the film-like solid material to gradually dissolve in the second polymer solution, forming a hydrogel.

[0055] When a film-like solid material containing a first polymer is contacted with a second polymer solution, the amount of the second polymer solution to be contacted with the film-like solid material is preferably selected so that a crosslinked structure is appropriately formed in the resulting hydrogel. Specifically, the amounts of the film-like solid material and the second polymer solution and the polymer concentrations are preferably adjusted so that the number of moles of functional group E in polymer (B) is preferably 0.1 to 10 moles, more preferably 0.2 to 8 moles, and even more preferably 0.5 to 2 moles per mole of carboxyl group in polymer (A).

[0056] When a dry material containing the water-soluble polymer (C) is obtained as an analgesic material, the water-soluble polymer (C) may be contained in the film-like solid or the second polymer solution. When the water-soluble polymer (C) is contained in the second polymer solution, the water-soluble polymer (C) may be blended in advance with the second polymer solution, and the second polymer solution containing the water-soluble polymer (C) may be brought into contact with the film-like solid. Alternatively, the film-like solid and the second polymer solution may be brought into contact with each other, and then the water-soluble polymer (C) may be added to the second polymer solution. From the viewpoint of favorable formation of a hydrogel, it is preferable that the second polymer solution contains the water-soluble polymer (C), and it is more preferable that the second polymer solution containing the water-soluble polymer (C) is brought into contact with the film-like solid.

[0057] When the second polymer solution containing the water-soluble polymer (C) is brought into contact with a film-like solid, the content of the water-soluble polymer (C) in the second polymer solution is preferably 0.01 to 50 parts by mass, more preferably 0.1 to 20 parts by mass, and even more preferably 0.5 to 15 parts by mass, per 100 parts by mass of the second polymer.

[0058] The resulting hydrogel is then dried to obtain the desired dried product. There are no particular limitations on the method for drying the hydrogel, and any known drying method can be used as appropriate. From the viewpoint of increasing adhesiveness to biological tissues and mechanical strength, freeze-drying is particularly preferred.

[0059] In the freeze-drying process, the freezing temperature is, for example, −70° C. to −5° C., preferably −60° C. to −5° C. The freeze-drying process conditions are not particularly limited, but it is preferably carried out at room temperature under reduced pressure. The pressure during the freeze-drying process is, for example, 50 Pa or less, preferably 20 Pa or less, and more preferably 10 Pa or less.

[0060] In this specification, the term "dry" refers not only to a state in which moisture has been completely removed, but also to a state in which moisture remains during the drying process. The moisture content of the dried product obtained by the drying treatment is, for example, 10% by mass or less, and preferably 5% by mass or less. When the obtained dried product is in the form of a film, the thickness of the dried product is, for example, 0.1 to 50,000 μm. This allows for the production of a dried product in which a hydrogel obtained by contacting a film-like solid containing one of the polymers (A) and (B) with a polymer solution containing the other polymer is dried.

[0061] (Regarding Method 2) In method [2], a solution containing polymer (A) is mixed with a solution containing polymer (B) in the presence of water-soluble polymer (C), and the resulting mixture is then dried to produce a dried product as an analgesic.

[0062] In the solution containing polymer (A) (hereinafter also referred to as "polymer solution A") and the solution containing polymer (B) (hereinafter also referred to as "polymer solution B"), examples of the solvent for dissolving the polymer include the same solvents as those exemplified as the solvent for dissolving the first polymer. Of these, it is preferable to use water alone from the viewpoint of efficiently performing the drying step. In polymer solution A and polymer solution B, the polymer concentration is, for example, 0.001 to 5% by mass, and preferably 0.01 to 1% by mass.

[0063] The amounts and concentrations of polymer solution A and polymer solution B are preferably adjusted so that the content of polymer (B) is 20 to 500 parts by mass per 100 parts by mass of polymer (A) in polymer solution A and polymer solution B. The amounts of polymer (A) and polymer (B) are more preferably 30 to 400 parts by mass, and even more preferably 50 to 300 parts by mass, per 100 parts by mass of polymer (A).

[0064] The water-soluble polymer (C) used in the method [2] can be the same as the specific examples of the water-soluble polymer (C) exemplified above. Among these, hyaluronic acid or a salt thereof can be preferably used. The amount of the water-soluble polymer (C) used is preferably 0.01 to 50 parts by mass, more preferably 0.1 to 20 parts by mass, and even more preferably 0.5 to 15 parts by mass, relative to 100 parts by mass of the polymer (A). The water-soluble polymer (C) is preferably used as an aqueous solution.

[0065] Subsequently, the mixed solution containing the polymer (A), polymer (B), and water-soluble polymer (C) obtained as described above is subjected to a drying treatment to obtain the target dried product. The drying treatment is preferably freeze-drying. Freeze-drying can be carried out according to a conventional method. For example, the mixed solution is placed in a mold and frozen, and the formed frozen product is freeze-dried to obtain the target product (dried product) having the desired shape. The moisture content of the dried product is, for example, 10% by mass or less, preferably 5% by mass or less.

[0066] <Specific embodiments of analgesic material> This analgesic material is a dry solid before use, but upon contact with water, it absorbs water and swells to become a hydrogel. That is, this analgesic material is a flexible dry body before contact with water, but upon contact with water, it changes from a dry body to a swollen body, thereby exhibiting adhesiveness to biological tissue. Here, water includes water, water-soluble organic solvents (e.g., ethanol), body fluids (e.g., saliva, blood, tissue fluid), and mixtures thereof. This analgesic material is not bioabsorbable and gradually decomposes and solubilizes under physiological conditions. Therefore, it is highly safe and can be left in the body while remaining adhered to biological tissue. This analgesic material is particularly suitable as an analgesic material to be applied to cover damaged areas of the skin or mucosa, such as stomatitis, burns, and trauma.

[0067] The shape of the analgesic material is not particularly limited, and it can be used in the form of, for example, a film, a sponge, a sheet, or a powder. The analgesic material may be provided in a state where it is held on a support, or in a state where it is enclosed in a package such as a film. The shape and material of the support are not particularly limited, and examples thereof include fabrics such as woven fabrics and nonwoven fabrics; and resin substrates such as polystyrene, polypropylene, and polyethylene. The films and sponges obtained using polymer (A) and polymer (B) have high mechanical strength and excellent flexibility, and therefore the analgesic material can be preferably used, among others, as a hydrogel-forming film or a hydrogel-forming sponge.

[0068] When applied to an injured area of ​​skin or mucosa, this analgesic material rapidly absorbs bodily fluids, such as saliva and tissue fluid, and firmly adheres to the tissue while absorbed. This allows the affected area to be quickly covered by the hydrogel, which contains sufficient bodily fluids. This allows the affected area to be quickly enveloped in bodily fluids, which is believed to result in pain relief from the initial stage of use. Furthermore, the hydrogel firmly adhering to the tissue allows the affected area to be enveloped in bodily fluids, which is believed to result in the sustained release of epidermal growth factor (EGF) from the surrounding bodily fluids to the affected area, promoting healing. This analgesic material is advantageous in that it can immediately relieve pain associated with injuries to the skin or mucosa, such as stomatitis, burns, and trauma, even without containing any medicinal ingredients. In particular, this analgesic material swells when it absorbs body fluids and adheres firmly to biological tissues, so the dressing can remain firmly attached to the affected area even in areas where dressings attached to the affected area tend to peel off, such as the inside of the mouth or the skin of the hands and feet, making it suitable as an analgesic for stomatitis, burns, and trauma. [Example]

[0069] The present invention will be specifically described below based on examples, but the present invention is not limited to these examples. In the following, "parts" and "%" mean "parts by mass" and "% by mass", respectively, unless otherwise specified.

[0070] [Example 1] A 1.2% cross-linked polyacrylic acid (Lubrizol, Carbopol 934P NF, hereinafter referred to as "PAA") aqueous solution (13 mL) was added to a 50 mm × 80 mm polypropylene container and dried at 70 ° C for 20 hours to prepare a PAA film. Next, a 5.5% polyvinylpyrrolidone (BASF, Kollidon 90F, polystyrene equivalent weight average molecular weight 320,000 (dimethylformamide eluent), hereinafter referred to as "PVP") aqueous solution (4.4 mL) and a 0.4% sodium hyaluronate (Kewpie, Hyaluronsan HA-LQH, hereinafter referred to as "HA") aqueous solution (15.8 mL) and a mixture of 4.9 mL of water were added dropwise to the surface of the PAA film, left to stand for 60 minutes, and then frozen at -50 ° C. The frozen product was freeze-dried at room temperature under reduced pressure (5 Pa) to obtain a hydrogel-forming sponge (size: 50 mm x 80 mm x 3 mm) as an analgesic material. The mixing ratio was PAA:PVP:HA = 1:1.53:0.4 (mass ratio). The obtained hydrogel-forming sponge was cut into pieces measuring 1 cm x 1 cm and attached to the affected areas of stomatitis of five monitors. The analgesic effect was evaluated according to the following criteria, and the average value for the five monitors was calculated. 5 points: Pain is reduced by half in less than an hour compared to when the product was not used. 3 points: The time it takes for the pain to decrease by half compared to when the product was not used is more than 1 hour but less than 3 hours 1 point: The time it takes for the pain to decrease by half compared to when the product was not used is between 3 hours and 5 hours. 0 points: Pain is reduced by half in more than 5 hours compared to when the product was not used, or there is no reduction in pain at all

[0071] [Example 2] A hydrogel-forming sponge was obtained as an analgesic material by the same operation as in Example 1, except that the types of raw materials were as shown in Table 1. The analgesic effect was evaluated in the same manner as in Example 1 using the obtained hydrogel-forming sponge.

[0072] [Comparative Examples 1 and 2] Commercially available stomatitis treatments, Stomatitis Patch Taisho A (manufactured by Taisho Pharmaceutical Co., Ltd.) or Traful Direct a (manufactured by Daiichi Sankyo Co., Ltd.), were applied to the stomatitis-affected areas of five monitors, and the analgesic effect was evaluated using the same criteria as in Example 1.

[0073] [Table 1]

[0074] Details of the compounds listed in Table 1 are shown below. PAA: Cross-linked polyacrylic acid (Lubrizol, Carbopol 934P NF) PVP: Polyvinylpyrrolidone (BASF, Kollidon 90F, polystyrene equivalent weight average molecular weight = 320,000 (dimethylformamide eluent)) PAAm: Polyacrylamide (MT Aquapolymer, Acofloc N-100, polystyrene equivalent weight average molecular weight = 17 million (dimethylformamide eluent)) HA: Sodium hyaluronate (Kewpie Corporation, Hyaluronsan HA-LQH)

[0075] <Evaluation results> As is clear from the results of Examples 1 and 2, the analgesic material containing polymer (A) and polymer (B) was able to significantly reduce the pain associated with stomatitis. In contrast, the stomatitis therapeutic agents of Comparative Examples 1 and 2 did not have a sufficient effect of reducing the pain associated with stomatitis.

Claims

1. a polymer (A) having a structural unit derived from an ethylenically unsaturated monomer having a carboxyl group; a polymer (B) (excluding the polymer (A)) having a structural unit derived from an ethylenically unsaturated monomer having a functional group capable of forming a hydrogen bond with a carboxyl group, the total amount of the polymer (A) and the polymer (B) is 70% by mass or more, A pain-relieving material that forms a hydrogel on contact with water.

2. The analgesic material according to claim 1, wherein the polymer (A) is a crosslinked polymer.

3. 3. The analgesic material according to claim 1, wherein the polymer (A) is poly(meth)acrylic acid.

4. The analgesic material according to any one of claims 1 to 3, wherein the polymer (B) has an amide group.

5. 5. The analgesic material according to claim 1, wherein the polymer (B) is at least one selected from the group consisting of polyvinylpyrrolidone and poly(meth)acrylamide.

6. The analgesic material according to any one of claims 1 to 5, which is used for stomatitis, burns or trauma.

7. A method for producing a painkiller, comprising: The analgesic material forms a hydrogel upon contact with water, a step of obtaining a film-like solid material containing one of a polymer (A) having a structural unit derived from an ethylenically unsaturated monomer having a carboxyl group and a polymer (B) having a structural unit derived from an ethylenically unsaturated monomer having a functional group capable of forming a hydrogen bond with a carboxyl group (excluding the polymer (A)); a step of contacting the film-like solid with a polymer solution containing the other of the polymer (A) and the polymer (B), and then drying the resulting mixture; Including, A method for producing a pain-relieving material, wherein the total amount of the polymer (A) and the polymer (B) contained in the pain-relieving material is 70 mass% or more.

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