WO2023217283A1 - 水凝胶及其制备方法和应用 - Google Patents

水凝胶及其制备方法和应用 Download PDF

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WO2023217283A1
WO2023217283A1 PCT/CN2023/094086 CN2023094086W WO2023217283A1 WO 2023217283 A1 WO2023217283 A1 WO 2023217283A1 CN 2023094086 W CN2023094086 W CN 2023094086W WO 2023217283 A1 WO2023217283 A1 WO 2023217283A1
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hydrogel
polymer
layer
cross
monomer
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French (fr)
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颜云松
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Priority to CN202380011908.XA priority Critical patent/CN117396541B/zh
Priority to EP23803051.4A priority patent/EP4461765A4/en
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    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
    • C08J3/00—Processes of treating or compounding macromolecular substances
    • C08J3/02—Making solutions, dispersions, lattices or gels by other methods than by solution, emulsion or suspension polymerisation techniques
    • C08J3/03—Making solutions, dispersions, lattices or gels by other methods than by solution, emulsion or suspension polymerisation techniques in aqueous media
    • C08J3/075—Macromolecular gels
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
    • A61K9/7007—Drug-containing films, membranes or sheets
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
    • C08F220/00—Copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and only one being terminated by only one carboxyl radical or a salt, anhydride ester, amide, imide or nitrile thereof
    • C08F220/02—Monocarboxylic acids having less than ten carbon atoms; Derivatives thereof
    • C08F220/04—Acids; Metal salts or ammonium salts thereof
    • C08F220/06—Acrylic acid; Methacrylic acid; Metal salts or ammonium salts thereof
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
    • C08J3/00—Processes of treating or compounding macromolecular substances
    • C08J3/28—Treatment by wave energy or particle radiation
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
    • C08J5/00—Manufacture of articles or shaped materials containing macromolecular substances
    • C08J5/18—Manufacture of films or sheets
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
    • C08J2333/00—Characterised by the use of homopolymers or copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and only one being terminated by only one carboxyl radical, or of salts, anhydrides, esters, amides, imides, or nitriles thereof; Derivatives of such polymers
    • C08J2333/02—Homopolymers or copolymers of acids; Metal or ammonium salts thereof
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
    • C08J2333/00—Characterised by the use of homopolymers or copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and only one being terminated by only one carboxyl radical, or of salts, anhydrides, esters, amides, imides, or nitriles thereof; Derivatives of such polymers
    • C08J2333/18—Homopolymers or copolymers of nitriles
    • C08J2333/20—Homopolymers or copolymers of acrylonitrile
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
    • C08J2401/00—Characterised by the use of cellulose, modified cellulose or cellulose derivatives
    • C08J2401/08—Cellulose derivatives
    • C08J2401/26—Cellulose ethers
    • C08J2401/28—Alkyl ethers

Definitions

  • the present invention relates to the field of material chemistry, and specifically to a hydrogel and its preparation method and application.
  • Hydrogels are cross-linked polymers dispersed in water and insoluble in water. Hydrogels can be made from natural or synthetic polymers. Hydrogels have the self-supporting viscoelastic ability to form a three-dimensional network of polymer chains when dispersed in water. Hydrogels also swell as their water content increases.
  • Hydrogels have been used in a variety of applications in the biomedical field, such as engineered scaffolds, medical diagnostic tools, therapeutic tools, drug delivery systems, and other applications.
  • a pharmaceutical drug can be loaded into a hydrogel, which will gradually migrate through the hydrogel structure until emerging from it.
  • composition and relative amounts of monomers in the hydrogel polymer can be altered to alter the diffusion and permeability properties of the drug-containing gel.
  • Several methods have been developed to introduce pharmaceutical agents into hydrogels. Some of these are drug entrapment during polymerization or introduction into the hydrogel during the water swelling stage. Drug release can occur through different types of external stimuli, such as pH changes, water influx into the gel, or other mechanisms. This type of drug delivery makes hydrogels an excellent choice for applications such as transdermal patches and wound care patches.
  • hydrogels have poor adhesion properties, which can be enhanced by secondary coating. Furthermore, another disadvantage of hydrogels is their low breaking strength, which limits the use of these materials in applications requiring special loading conditions. Another typical disadvantage of hydrogels is their lack of durability due to water loss. In addition, existing hydrogels have low transparency and air permeability. Finally, it's hard Find a compromise between the high release rate of the drug and the duration of the material's effectiveness over time.
  • the purpose of the present invention is to provide a hydrogel with better adhesive properties, mechanical properties, durability properties, transparency and air permeability.
  • the hydrogel of the present invention is characterized in that the hydrogel contains water, glycerin, cellulose ether and polymer; the polymer includes a first polymer and a second polymer; The first polymer is polyacrylonitrile, and the second polymer is cross-linked polyacrylic acid or cross-linked polyN-hydroxyethylacrylamide.
  • the present invention provides a premix for preparing the above hydrogel, the premix containing water, glycerol, cellulose ether, acrylonitrile monomer, acrylic acid monomer and cross-linking agent monomer;
  • the premix contains water, glycerol, cellulose ether, acrylonitrile monomer, N-hydroxyethylacrylamide monomer and cross-linker monomer.
  • the present invention provides a method for preparing a hydrogel, which method includes: mixing the premix with a photoinitiator and then photocuring.
  • the present invention provides a method for preparing hydrogel, which method includes:
  • the step is to use a second layer (141) located in the second hydrophobic material (141a).
  • the third layer of the trihydrophobic material (143a) (143)
  • the second mixture (13 or 16) is exposed to UV light in the mold (23) which is subjected to pressure and covered by the third layer (143) to obtain the hydrogel containing polyacrylonitrile (24).
  • the present invention also provides a pharmaceutical composition, which contains the hydrogel as described above and pharmaceutical active ingredients.
  • the present invention also provides the use of the hydrogel as described above in the preparation of sensors, actuators, transistors, capacitors, clothing materials and batteries.
  • the present invention provides a hydrogel with better adhesive properties, mechanical properties, durability properties, transparency and air permeability, and also has excellent drug loading properties and drug sustained release properties.
  • This hydrogel can be at least one of a transdermal patch, a wound care patch, a skin care patch and a tissue regeneration patch, and can be used in fields such as medicine and biology, medical beauty, and skin care.
  • Figure 1 depicts the steps for preparing the reagent mixture for membrane 1.
  • Figure 2 depicts the steps for preparing the reagent mixture for membrane 2.
  • Figure 3 depicts the steps of introducing the reactant mixture into the mold, polymerizing and obtaining the hydrogel film.
  • Figure 4 depicts the steps for removing the hydrogel film from the mold.
  • Figure 5 is an exemplary stretched photograph of hydrogel film 1.
  • a first aspect of the present invention provides a hydrogel, which contains water, glycerin, cellulose ether and a polymer; the polymer includes a first polymer and a second polymer; the first polymer is poly Acrylonitrile, the second polymer is cross-linked polyacrylic acid or cross-linked polyN-hydroxyethylacrylamide.
  • the role of cellulose ether in the hydrogel is to encapsulate the drug and the drug delivery channel, and also serve as a tackifier and water-retaining agent;
  • the role of polyacrylonitrile and the second polymer in the hydrogel is to increase the mechanical properties of the hydrogel. Elasticity and increased drug solubility.
  • the possible reason why the above-mentioned special effects have better adhesive properties, mechanical properties, durability properties, transparency and air permeability of the hydrogel of the present invention lies in the mechanical stability formed by polyacrylonitrile and the second polymer in the hydrogel.
  • the dual network structure, as well as the water retention and adhesion power of the cellulose material itself, give the polymer adhesive properties, mechanical properties, durability properties, transparency and breathability.
  • the solid content of the hydrogel is 20-35% by mass, preferably 22-25% by mass.
  • the solid content of the hydrogel can be measured by dividing the solid weight of the gel obtained after drying by the total weight of the gel before drying.
  • the weight ratio of the cellulose ether to the polymer can be 1: (5-9); in order to further improve the performance of the hydrogel, the weight ratio of the cellulose ether to the polymer is preferably is 1: (5-8).
  • the composition of the hydrogel in order to meet the requirements for better mechanical properties, can be adjusted such that the weight ratio of the cellulose ether to the polymer is 1: (7-9) .
  • the composition of the hydrogel in order to meet the requirements for better viscosity, can be adjusted such that the weight ratio of the cellulose ether to the polymer is 1: (5-6) .
  • the cellulose can be methyl cellulose, hydroxyethyl methyl cellulose, carboxymethyl cellulose, ethyl cellulose, benzyl cellulose, hydroxyethyl cellulose, hydroxypropyl methyl cellulose , at least one of cyanoethyl cellulose, benzyl cyanoethyl cellulose, carboxymethyl hydroxyethyl cellulose, phenyl cellulose and nanocellulose.
  • the cellulose is preferably 2-hydroxyethyl cellulose.
  • the role of 2-hydroxyethylcellulose in hydrogels is to increase the viscosity of the gel and also have the function of loading and drug delivery.
  • the possible reason why the above-mentioned special effects have better adhesive properties, mechanical properties, durability, transparency and air permeability of the hydrogel of the present invention is that its substituent groups are more likely to bond with water to form internal hydrogen bonds. .
  • the molar substitution degree of the 2-hydroxyethyl cellulose can be 2-3, preferably 2.4-2.6; the viscosity of the 2 mass% concentration aqueous solution of the 2-hydroxyethyl cellulose at 25°C is 110-137mPa ⁇ S, preferably 115-125mPa ⁇ S.
  • the weight ratio between the polyacrylonitrile and the cross-linked polyacrylic acid is 1: (5-15), preferably 1: (7-12), more preferably 1: (9) -11).
  • the weight ratio of the polyacrylonitrile and the cross-linked polyN-hydroxyethylacrylamide is 1: (1-20), preferably 1: (2-10), more preferably 1: (3-7 ).
  • the cross-linked polyacrylic acid monomers may include acrylic acid monomers and cross-linking agent monomers;
  • the cross-linked poly-N-hydroxyethylacrylamide monomers may include N-hydroxyethylacrylamide monomers. body and cross-linker monomers.
  • the cross-linking agent monomer may be at least one of ethylene glycol dimethacrylate and polyethylene glycol acrylate, preferably ethylene glycol dimethacrylate.
  • the acrylonitrile copolymer is a polymer obtained by photopolymerization;
  • the photoinitiator used in the photopolymerization includes 2,2-dimethoxy-2-phenylacetophenone, benzoin, benzoin dimethyl ether, Benzoin ethyl ether, benzoin isopropyl ether, benzoin butyl ether, diphenylethyl ketone, ⁇ , ⁇ -dimethoxy- ⁇ - Phenylacetophenone, ⁇ , ⁇ -diethoxyacetophenone, ⁇ -hydroxyalkylphenone, ⁇ -aminoalkylphenone, aroylphosphine oxide, bisbenzoylphenylphosphine oxide, At least one of benzophenone, Michler's ketone and ammonium persulfate.
  • the photoinitiator used in the photopolymerization may be used at a concentration of 1-3% by weight.
  • the content of glycerol in the hydrogel may be 20-40% by volume, preferably 22-31% by volume.
  • the present invention also provides a premix for preparing the hydrogel as described above, the premix containing water, glycerin, cellulose ether, acrylonitrile monomer, acrylic acid monomer and cross-linking agent monomer; Alternatively, the premix contains water, glycerol, cellulose ether, acrylonitrile monomer, N-hydroxyethylacrylamide monomer and cross-linker monomer.
  • the present invention also provides a method for preparing a hydrogel, which method includes: mixing the above premix with a photoinitiator and then photocuring.
  • the invention also provides a method for preparing hydrogel, which method includes:
  • the step is to use a second layer (141) located in the second hydrophobic material (141a).
  • the second mixture (13 or 16) is exposed to UV light in the mold (23) which is subjected to pressure and covered by the third layer (143) to obtain the hydrogel containing polyacrylonitrile (24).
  • the preparation steps of the first solution (3) include dissolving 0.6 to 1.4 grams of 2-hydroxyethyl cellulose (4) per 17 ml and 23 ml of water (5), and mechanically mixing the phases before The first solution (3) is stirred for a subsequent period of 22 to 26 hours.
  • the photoinitiator (7) contains 2,2-dimethoxy-2-phenylacetophenone (70).
  • the preparation step of the second solution (6) includes dissolving 94 mg to 106 mg of ethanol (6a) in a volume of 1.8 ml to 2.2 ml within a period of 60 minutes to 180 minutes before the mixing step. mg of the 2,2-dimethoxy-2-phenylacetophenone (70).
  • the preparation step of the first mixture (8) includes proportionally adding the acrylic acid (9) whose volume can vary between 475 ⁇ L and 625 ⁇ L and the acrylonitrile (10) which can vary between 60 ⁇ L and 210 ⁇ L. ), then (5) add a volume of said ethylene glycol dimethacrylate (11) between 18 ⁇ L and 25 ⁇ L and a volume of said glycerol (12) between 750 ⁇ L and 1200 ⁇ L, and the appropriate
  • the subsequent mixing step to obtain the second mixture (13) consists of adding a volume of said first solution (3) between 1.2 mL and 3.3 mL to said first mixture (8) in a volume of between 1.2 mL and 3.3 mL. , followed by mechanical stirring lasting between 60 and 180 minutes, and from the subsequently added volume of the photoinitiator (7) between 20 ⁇ L and 180 ⁇ L.
  • the filling step includes pouring 0.8 ml to 2 ml of the second mixture (13) into the mold (23), the frame (142) has a thickness between 100 microns and 250 microns, and In the synthesis stage called photopolymerization by UV irradiation, carried out at a wavelength between 300 nm and 380 nm, with a time varying between 90 and 150 min, and an intensity between 75 mW/cm2 and 110 mW /cm2.
  • the frame (142) includes polydimethylsiloxane.
  • the first hydrophobic material (140a) includes organic glass
  • the second hydrophobic material (141a) includes polytetrafluoroethylene
  • the third hydrophobic material (143a) includes organic glass
  • said mold (23) is also provided with a fourth layer containing said second hydrophobic material (141a) sandwiched between said third layer (143) and said frame (142) during said closing phase (144) closed.
  • the present invention also provides a pharmaceutical composition, which further contains the hydrogel and pharmaceutical active ingredients as described above.
  • the pharmaceutical composition is at least one of a transdermal patch, a wound care patch, a skin care patch and a tissue regeneration patch, and is used in fields such as medicine and biology, medical beauty, and skin care.
  • the present invention also provides the use of the hydrogel as described above in the preparation of sensors, actuators, transistors, capacitors, clothing materials and batteries.
  • the method for preparing a hydrogel membrane (1) includes several steps, as shown in Figures 1 and 3.
  • the first step involves preparing a first solution (3) containing 2-hydroxyethylcellulose (4) and water (5).
  • a certain amount of 2-hydroxyethylcellulose (4) is preferably dissolved, for each volume of water (5 ), preferably 0.6g to 1.4g, more preferably 0.8g to 1.2g.
  • the first 3 solutions are then mechanically stirred for a period of 22 hours to 26 hours, or more preferably 23 hours to 25 hours, before the next step of the process, in which the first 3 solutions are combined with the other prepared The solution is mixed.
  • 2-Hydroxyethylcellulose (4) is intended to impart a framework structure of controlled size to the hydrogel. This characteristic of 2-hydroxyethylcellulose (4) allows hydrogels to be advantageously used in biomedical applications to gradually release drugs while providing sufficient adhesion and water retention capabilities.
  • the subsequent step of the method preferably consists in preparing a second solution (6) containing a polymerization photoinitiator (7).
  • a second solution (6) is required to achieve the next step of polymerization, which is advantageously activated by a photoinitiator (7).
  • the photoinitiator (7) preferably contains 2,2-dimethoxy-2-phenylacetophenone (70). 2,2-Dimethoxy-2-phenylacetophenone (70) is particularly suitable for producing relatively low reactive species sufficient to polymerize the monomers used in the process.
  • This step of preparing the second solution (6) preferably includes dissolving 94 mg to 106 mg or more preferably 97 mg to Between 103 mg of 2,2-dimethoxy-2-phenylacetophenone (70) in a time range of 60 minutes to 180 minutes or more preferably between 90 minutes and 150 minutes before the next mixing step.
  • the use of ethanol 6a and the times shown increases the stability of 2,2-dimethoxy-2-phenylacetophenone 70 because this species is expected to be used for the initiation reaction.
  • the next step of the process consists in preparing a first mixture (8) comprising acrylic acid (9), acrylonitrile (10), ethylene glycol dimethacrylate (11) and glycerol (12).
  • Acrylic acid (9) and acrylonitrile (10) are the monomers that will form the final polymer structure together with ethylene glycol dimethacrylate (11) and glycerol (12), inducing the formation of polymer chains.
  • the step of preparing the first mixture (8) preferably includes the proportional addition of acrylic acid (9 ) and acrylonitrile (10) varying between 60 ⁇ L and 210 ⁇ L or more preferably between 150 ⁇ L and 190 ⁇ L, preferably followed by a volume of 18 ⁇ L to 25 ⁇ L or more preferably 19 ⁇ L to 24 ⁇ L or more preferably 19 ⁇ L to 23 ⁇ L of dimethyl ethylene glycol acrylate (11) and a volume of 750 ⁇ L to 1200 ⁇ L or more preferably 850 ⁇ L to 1000 ⁇ L or more preferably 900 ⁇ L to 1000 ⁇ L of glycerol 12.
  • the next stage of the process consists of mixing the first solution (3), the second solution (6) and the first mixture (8) to obtain the second mixture (13).
  • the mixing step preferably includes adding to the first mixture (8) a volume of the first solution of between 1.2 ml and 3.3 ml, or more preferably between 1.2 ml and 2.5 ml, or more preferably between 1.6 ml and 2.5 ml. 3. Subsequent mechanical stirring is preferably from 60 minutes to 180 minutes, or more preferably from 60 minutes to 90 minutes to 150 minutes. Once the mechanical stirring is complete, a volume of the second solution (6) is finally added, preferably between 20 ⁇ L and 130 ⁇ L, or more preferably between 20 ⁇ L and 60 ⁇ L, or more preferably between 20 ⁇ L and 40 ⁇ L.
  • the method advantageously includes the step of filling with the second mixture 13 a mold (23) consisting of a first layer 140 of a first hydrophobic material 140a, a third layer located on and adhered to the first layer 140a.
  • the first layer 140 is therefore the base of the mould, and is preferably covered by a second layer 141 on which the second closing mixture (13) is poured from the frame 142.
  • the first layer 140 consists of a first hydrophobic material 140a, which does not bond since the second mixture (13) needs to be in contact with it.
  • the first hydrophobic material 140a preferably includes organic glass
  • the second hydrophobic material 141a preferably includes polytetrafluoroethylene.
  • These two materials have optimal properties to perform the functions contained in the second mixture (13) while maintaining chemical inertness requirements. Both materials can be used in thin layers.
  • the first layer 140 and the second layer 141 preferably have two surface dimensions with a length preferably between 10 cm and 20 cm, more preferably between 12 cm and 18 cm.
  • the frame 142 of the mold (23) is a hollow layer in the central part into which the second mixture (13) is injected, and preferably has two lateral dimensions that are the same size as those of the first layer 140 and the second layer 141 .
  • frame 142 preferably includes polydimethylsiloxane. This material offers flexibility, chemical inertness and easy removal at the end of the process.
  • the filling step preferably includes filling the mold (23) with a volume of between 0.8 ml and 2 ml or more preferably between 1 ml and 1.7 ml of the second mixture (13) and the frame 142 has between 100 ⁇ m and 250 ⁇ m or more preferably 150 ⁇ m. and 230 ⁇ m thickness.
  • the filling stage of the mold (21) has the function of giving the second mixture (13) the final shape that the product must have.
  • the stage for closing the mold (23) is followed by a third layer 143 made of a third hydrophobic material 143a, preferably organic and/or in A hydrophobic material 140a, preferably solid glass, can perform a covering function.
  • the third layer 143 is placed suitably, preferably finely, on the frame 142 which surrounds the mixture (13) present therein.
  • the covering layer has the function of giving the final product the correct shape during the subsequent synthesis stages, so it must ensure the same chemically inert properties as the rest of the mold (23).
  • the mold (23) is also closed with a quarter layer 144, which also includes a hydrophobic material, preferably PTFE, sandwiched between the third layer 143 and the frame 142, more Preferably consists of second hydrophobic material 141a.
  • Mold closing can be assisted by lateral mechanical supports, additional external upper or lower supports, and more supports. After the closing step of the mold (23), a pressing step of the mold follows.
  • the mold (23) is closed and contains the mixture (13).
  • the mechanical pressure on the mold (23) will preferably be maintained throughout the subsequent synthesis stage.
  • the third layer (143) is suitably placed in intimate contact with the mixture (13).
  • the latter is preferably in intimate contact with the mixture (13).
  • the next step consists in synthesizing said film (1) by photopolymerization, which is exposed to UV light while the second mixture (13) is subjected to pressure in the mold (23) and covered by a third layer (143) Proceed to obtain a membrane (1) made of a hydrogel containing polyacrylonitrile (24).
  • the polymerization proceeds via the reactive species generated by the photoinitiator (7) upon absorption of UV radiation. Therefore, the efficiency of the polymerization process depends on the UV radiation level. Therefore, it is preferred to use a reduced third thick layer (143) to limit the absorption of radiation and allow the second mixture (13) to absorb most of the radiation. Where the procedure for adding the fourth layer (144) is provided, the latter must also have a reduced thickness, ie preferably less than 200 ⁇ m.
  • the wavelength of photopolymerization by irradiation of ultraviolet rays is preferably between 300 nanometers and 380 nanometers or more preferably between 350 nanometers and 370 nanometers, and the time range is between 90 minutes and 150 minutes or more preferably 100 minutes and 135 minutes or more preferably between 110 minutes and 130 minutes, the intensity range is between 75 mW/cm2 and 110 mW/cm2 or more preferably between 85 mW/cm2 and 100 mW/cm2 between.
  • the photopolymerization process allows to obtain films (1) with desired properties.
  • the method for preparing the hydrogel membrane (2) includes several steps, as shown in Figures 2 and 3.
  • the first step involves preparing a first solution (3) containing 2-hydroxyethylcellulose (4) and water (5).
  • a certain amount of 2-hydroxyethylcellulose (4) is preferably dissolved, for each volume of water (5 ), preferably 0.6g to 1.4g, more preferably 0.8g to 1.2g.
  • the first 3 solutions are then mechanically stirred for a period of 22 hours to 26 hours, or more preferably 23 hours to 25 hours, before the next step of the process, in which the first 3 solutions are combined with the other prepared The solution is mixed.
  • 2-Hydroxyethylcellulose (4) is intended to impart a framework structure of controlled size to the hydrogel. This characteristic of 2-hydroxyethylcellulose (4) allows hydrogels to be advantageously used in biomedical applications to gradually release drugs while providing sufficient adhesion and water retention capabilities.
  • the subsequent step of the method preferably consists in preparing a second solution (6) containing a polymerization photoinitiator (7).
  • a second solution (6) is required to achieve the next step of polymerization, which is advantageously activated by a photoinitiator (7).
  • the photoinitiator (7) preferably contains 2,2-dimethoxy-2-phenylacetophenone (70). 2,2-Dimethoxy-2-phenylacetophenone (70) is particularly suitable for producing relatively low reactive species sufficient to polymerize the monomers used in the process.
  • This step of preparing the second solution (6) preferably includes between 60 minutes and 180 minutes or more preferably 90 minutes for each volume of ethanol 6a between 1.8 mL and 2.2 mL or more preferably between 1.9 mL and 2.1 mL before the next mixing step. From 94 mg to 106 mg or more preferably from 97 mg to 103 mg of 2,2-dimethoxy-2-phenylacetophenone (70) is dissolved in a time period from 150 minutes to 150 minutes. The use of ethanol 6a and the times indicated increased the stability of 2,2-dimethoxy-2-phenylacetophenone (70) since use of this material was anticipated.
  • the next step of the process consists in preparing a first mixture (15) comprising N-hydroxyethylacrylamide (14), acrylonitrile (10), ethylene glycol dimethacrylate (11) and glycerol (12).
  • N-Hydroxyethylacrylamide (14) and acrylonitrile (10) are the monomers that will form the final polymer structure together with ethylene glycol dimethacrylate (11) and glycerol (12), which induce polymer chains Formation.
  • the step of preparing the first mixture preferably consists in proportionally adding a volume of N-Hydroxyethylacrylamide (14) varying between 700 ⁇ L and 1000 ⁇ L or more preferably between 750 ⁇ L and 950 ⁇ L or more preferably between 720 ⁇ L and 750 ⁇ L and varying between 60 ⁇ L and 210 ⁇ L or more preferably 150 ⁇ L and 190 ⁇ L of acrylonitrile (10), preferably followed by a volume of 18 ⁇ L to 25 ⁇ L or more preferably 19 ⁇ L to 24 ⁇ L or more preferably 20 ⁇ L to 23 ⁇ L of ethylene glycol dimethacrylate (11) and a volume of 750 ⁇ L to 880 ⁇ L or more preferably 770 ⁇ L to 850 ⁇ L or more preferably 780 ⁇ L to 1200 ⁇ L of glycerol (12).
  • a volume of N-Hydroxyethylacrylamide (14) varying between 700 ⁇ L and 1000
  • the next stage of the process consists of mixing the first solution (3), the second solution (6) and the first mixture (15) to obtain the second mixture (16).
  • the mixing step preferably includes adding to the first mixture (15) a volume of the first solution of between 1.2 ml and 2.3 ml, or more preferably between 1.2 ml and 2.5 ml, or more preferably between 1.6 ml and 2.5 ml. (3), followed by mechanical stirring for preferably 60 minutes to 180 minutes, or more preferably 60 minutes to 90 minutes to 150 minutes. Once the mechanical stirring is complete, a volume of the second solution (6) is finally added, preferably between 20 ⁇ L and 130 ⁇ L, or more preferably between 20 ⁇ L and 60 ⁇ L, or more preferably between 20 ⁇ L and 40 ⁇ L.
  • the method advantageously includes the step of filling with the second mixture (16) a mold (23) consisting of a first layer 140 of a first hydrophobic material 140a, located on and adhered to the first layer 140 It consists of a second layer 141 of a second hydrophobic material 141a, a second layer 142 capable of performing the function of a synthetic platform, and a frame 142 located on the second layer 141.
  • the first layer 140 is therefore the base of the mould, and is preferably covered by a second layer 141 on which the second sealing mixture (16) is poured from the frame 142.
  • the first layer 140 consists of a first hydrophobic material 140a which does not bond since the second mixture (16) needs to be in contact with it.
  • the first hydrophobic material 140a preferably includes organic glass
  • the second hydrophobic material 141a preferably includes polytetrafluoroethylene.
  • These two materials have optimal properties to perform the functions contained in the second mixture (16) while maintaining chemical inertness requirements. Both materials can be used in thin layers.
  • the first layer 140 and the second layer 141 preferably have two surface dimensions with a length preferably between 10 cm and 20 cm, more preferably between 12 cm and 18 cm.
  • the frame 142 of the mold 14 is A hollow layer in the central part into which the second mixture (16) is injected, and preferably has two lateral dimensions that are the same size as those of the first layer 140 and the second layer 141.
  • frame 142 preferably includes polydimethylsiloxane. This material offers flexibility, chemical inertness and easy removal at the end of the process.
  • the filling step preferably includes filling the mold (23) with a volume of between 0.8 ml and 2 ml or more preferably between 1 ml and 1.7 ml of the second mixture (16) and the frame 142 has between 100 ⁇ m and 250 ⁇ m or more preferably 150 ⁇ m. and 230 ⁇ m thickness.
  • the filling stage of the mold 14 has the function of giving the second mixture (16) the final shape that the product must have.
  • the stage for closing the mold (23) is followed by a third layer 143 made of a third hydrophobic material 143a, preferably organic and/or in A hydrophobic material 140a, preferably solid glass, can perform a covering function.
  • the third layer 143 is placed suitably, preferably finely, on the frame 142 which surrounds the mixture (16) present therein.
  • the covering layer has the function of giving the final product the correct shape during the subsequent synthesis stages, so it must ensure the same chemically inert properties as the rest of the mold (23).
  • the mold (23) is also closed with a quarter layer 144, which also includes a hydrophobic material, preferably PTFE, sandwiched between the third layer 143 and the frame 142, more Preferably consists of second hydrophobic material 141a.
  • Mold closing can be assisted by lateral mechanical supports, additional external upper or lower supports, and more supports.
  • the pressing step of the mold (23) follows the closing step of the containing mixture (16).
  • a pressure is mechanically applied to the mold (23), which pressure is preferably maintained throughout the subsequent synthesis stages.
  • the third layer 143 is suitably placed in intimate contact with the mixture (16).
  • the latter is preferably in intimate contact with the mixture ( 16 ).
  • the next step consists in synthesizing said film (2) by photopolymerization which takes place while the second mixture (16) is subjected to pressure in the mold (23) and covered by a third layer 143, exposed to UV light, A membrane (2) made of a hydrogel containing polyacrylonitrile (24) is thus obtained.
  • the polymerization proceeds via the reactive species generated by the photoinitiator (7) upon absorption of UV radiation. Therefore, the efficiency of the polymerization process depends on the UV radiation level. Therefore, it is preferred to use a reduced third thick layer 143 to limit the absorption of radiation and allow the second mixture 16 to absorb most of the radiation. In a variant of the procedure for adding the fourth layer 144 , the latter must also have a reduced thickness, ie preferably less than 200 ⁇ m.
  • the wavelength of photopolymerization by irradiation of ultraviolet rays is preferably between 300 nanometers and 380 nanometers or more preferably between 350 nanometers and 370 nanometers, and the time range is between 90 minutes and 150 minutes or more preferably 100 minutes and 135 minutes or more preferably between 110 minutes and 130 minutes, the intensity range is between 75 mW/cm2 and 110 mW/cm2 or more preferably between 85 mW/cm2 and 100 mW/cm2 between.
  • the photopolymerization process allows to obtain films (2) with desired properties.
  • a step of removing the third layer 143 and the mold (23) is performed.
  • residues of the second mixture (16) are also removed, remaining inside the mold (23) which were not present during the synthesis phase. reaction. Residue must be removed as it changes the properties of the film (2).
  • membranes (1) and (2) since they are obtained by following the procedure described, have properties that make them more advantageous than existing hydrogel membranes.
  • Membrane (1) and membrane (2) have better adhesive properties than existing hydrogel membranes derived from, in addition to those properties resulting from the interaction of carboxyl and hydroxyl functional groups Its special secondary structural properties. This superior performance can lead to a significantly improved experience for patients with wound recovery needs (such as: surgical wounds after surgery, traumatic wounds and burn treatment) and medical applications in difficult-to-treat areas (such as: joints and extremities) .
  • Membrane (1) and membrane (2) exhibit the property of gradual release of chemical compounds, which can be compared to the current There are films that are better integrated into their structure. Membranes (1) and (2) have greater release rates without a significant decrease in release efficiency over time, contrary to what is known to occur in membranes. This property is mainly due to the fact that the pore size and gradient of the 2-hydroxyethylcellulose (4) structure can be adjusted depending on how the synthesis process is adjusted. These properties make membrane (1) and membrane (2) particularly suitable for applications where a gradual release effect of pharmaceutical agents is required, such as transdermal patches.
  • membrane (1) and membrane (2) through their high optical transparency, allow the inspection of possible wounds in contact with them without having to remove them. Furthermore, membrane (1) and membrane (2) have a durability exceeding 6 months when exposed to air. Film (1) and film (2) also have good air permeability. In biomedical applications such as plasters, this property can create a favorable microenvironment for cell proliferation and improve the effectiveness of the dressing.
  • hydrogel membrane (1) and membrane (2) Another characteristic of the hydrogel membrane (1) and membrane (2) is the mechanical properties, which are superior to existing membranes in terms of breaking strength and Young's modulus. This feature makes the membrane (1) and membrane (2) according to the invention very advantageous, since better mechanical properties extend the application fields of this material to electronic devices, tissue engineering, adhesives, coatings and wearable sensors. This advantage is made possible by the presence of complementary networks of polyacrylonitrile or interpenetrating systems with structures called SNIPSy.
  • the ability to load chemicals will also provide potential industrial applications such as sensors, actuators, transistors, capacitors, clothing materials, and batteries as support platforms.
  • This example is used to illustrate the preparation process of the hydrogel membrane.
  • the pre-polymerization material which is a premix.
  • the mass ratio of 2-hydroxyethyl cellulose, acrylic acid, acrylonitrile and ethylene glycol dimethacrylate is 125:508:106:19.
  • the pre-polymerization material is mixed with the photoinitiator (an ethanol solution of 2,2-dimethoxy-2-phenylacetophenone, the usage concentration is 2% by weight) and then introduced into the mold for photopolymerization.
  • the wavelength of photopolymerization is 360 nm, time 120 minutes, intensity 90 mW/cm2, then remove the mold to obtain hydrogel film 1.
  • hydrogel film 1 obtained in Example 1 was evaluated for adhesive properties and mechanical properties. test. The results are shown in Table 1. An exemplary tensile photograph of hydrogel film 1 is shown in Figure 5.
  • the hydrogel film 1 obtained in Example 1, the hydrogel film 2 obtained in Example 2, the hydrogel film C1 obtained in Comparative Example 1, and the hydrogel film C2 obtained in Comparative Example 2 were tested for drug loading and drug release.
  • the drug used was lidocaine, and the results are shown in Table 2.
  • the present invention provides a hydrogel with better adhesive properties, mechanical properties, durability, transparency and air permeability, and also has excellent drug loading properties and sustained drug release. performance.
  • Comparative Example C3 nor Comparative Example C4 could form a gel.
  • C2 colloid is not stable and rapidly disintegrates during release, so no valid data can be obtained.
  • the mixture of Comparative Example C4 hardened in less than 10 hours, indicating that the water retention effect of glycerol is extremely important. Not only that, glycerin is also extremely important for the formation of colloids.
  • polyacrylic acid is crucial to the three-dimensional main structure of the colloid.
  • hydrogel film 1 and Comparative Example C1 polyacrylonitrile can significantly reduce the Young's constant of the polymer's mechanical properties, significantly reduce the colloid's restoring force during the stretching process, and improve the mechanical properties.
  • 2-hydroxyethyl cellulose has obviously improved the colloid's adhesion and water retention properties.
  • Both Hydrogel Film 1 and Hydrogel Film 2 can prove that cross-linked poly-N-hydroxyethylacrylamide and acrylic acid are the main bodies of the colloidal 3D structure.
  • any combination of various embodiments of the present invention can also be carried out. As long as they do not violate the idea of the present invention, they should also be regarded as the disclosed content of the present invention.

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Abstract

本发明提供了水凝胶，该水凝胶含有水、甘油、纤维素醚和聚合物；所述聚合物包括第一聚合物和第二聚合物；所述第一聚合物为聚丙烯腈，所述第二聚合物为交联的聚丙烯酸或交联的聚N-羟乙基丙烯酰胺。本发明还提供了用于制备该水凝胶的预混物和制备该水凝胶的方法。本发明还提供了一种药物组合物。该药物组合物可以为透皮贴片、伤口护理贴片、皮肤护理贴片和组织再生贴片中的至少一种，应用于医药生物、医美、护肤等领域。本发明还提供了如上所述的水凝胶在制备传感器、执行器、晶体管、电容器、服装材料和电池中的用途。本发明提供的水凝胶具有更好的粘合性能、机械性能、耐久性能、透明性和透气性，并且还具有优良的载药性能和药物缓释性能。

Description

水凝胶及其制备方法和应用 技术领域
本发明涉及材料化学领域，具体地，涉及一种水凝胶及其制备方法和应用。
背景技术
水凝胶是分散在水中且不溶于水的交联聚合物。水凝胶可以由天然或合成聚合物制成。水凝胶分散在水中时，具有形成聚合物链的三维网络自支撑粘弹性的能力。水凝胶还会随着含水量的增加而膨胀。
水凝胶已经在生物医学领域的各种应用中得到应用，例如工程支架、医学诊断工具、治疗工具、药物释放系统和其他应用。
特别地，由于水凝胶内部的互连结构，在药物试剂的逐渐释放系统中的应用成为可能。因此，通过合适的合成方法，可以将药剂药物加载到水凝胶中，该药剂药物将逐渐迁移通过水凝胶结构，直到从其中出来。
可以改变水凝胶聚合物中单体的组成和相对量，以改变含有药物的凝胶的扩散和渗透特性。已经开发了几种在水凝胶中引入药物试剂的方法。其中一些是聚合过程中的药物截留或在水溶胀阶段引入水凝胶。药物的释放可通过不同类型的外部刺激发生，如pH值变化、水流入凝胶或其他机制。这种类型的药物传递使水凝胶成为透皮贴剂和伤口护理贴剂等应用的最佳选择。
然而，水凝胶的主要缺点在于其较差的粘附性能，这可以通过二次涂覆来增强。此外，水凝胶的另一缺点是断裂强度低，这限制了这些材料在需要特殊载荷条件的应用中的使用。水凝胶还有一个典型缺点是由于失水而缺乏耐久性。此外，已有的水凝胶的透明性和透气性较低。最后，很难 在药物的高释放速率和材料随时间的有效性持续时间之间找到折衷方案。
发明内容
本发明的目的是提供一种粘合性能、机械性能、耐久性能、透明性和透气性更好的水凝胶。
为了实现上述目的，一方面，本发明水凝胶，其特征在于，该水凝胶含有水、甘油、纤维素醚和聚合物；所述聚合物包括第一聚合物和第二聚合物；所述第一聚合物为聚丙烯腈，所述第二聚合物为交联的聚丙烯酸或交联的聚N-羟乙基丙烯酰胺。
另一方面，本发明提供了一种用于制备上述水凝胶的预混物，该预混物含有水、甘油、纤维素醚、丙烯腈单体、丙烯酸单体和交联剂单体；或者，该预混物含有水、甘油、纤维素醚、丙烯腈单体、N-羟乙基丙烯酰胺单体和交联剂单体。
另一方面，本发明提供了一种制备水凝胶的方法，该方法包括：将所述预混物与光引发剂混合后进行光固化。
另一方面，本发明提供了一种制备水凝胶的方法，该方法包括：
-制备包含2-羟乙基纤维素(4)和水(5)的第一溶液(3)的步骤，
-制备包含光引发剂(7)固化的第二溶液(6)的步骤，
-制备包含丙烯酸(9)或N-羟乙基丙烯酰胺(14)、丙烯腈(10)、二甲基丙烯酸乙二醇酯(11)和甘油(12)的第一混合物(8或15)的步骤，
--所述第一溶液(3)、所述第二溶液(6)和所述第一混合物(8或15)的混合步骤，以获得第二混合物(13或16)，
--用所述第二混合物(13或16)填充模具(23)的步骤，所述第二混合物(13或16)由位于第一疏水材料(140a)中的第一层(140)、位于所述第一层(140)上的位于第二疏水材料(141a)中的第二层(141)和位于所述第二层上的框架(142)组成，所述步骤-用位于所述第三疏水材料(143a)中的第三层 (143)封闭所述模具(23)的步骤；
-所述模具(23)的压制步骤，在所述闭合步骤之后，
-所述膜(1或2)的通过光聚合的合成步骤，所述光聚合通过以下步骤进行；
所述第二混合物(13或16)在经受压力并被所述第三层(143)覆盖的所述模具(23)中用紫外线曝光，以获得包含聚丙烯腈(24)的所述水凝胶膜(1或2)，
-去除所述第三层(143)和所述模具(23)的步骤。
本发明还提供了一种药物组合物，该药物组合物含有如上所述的水凝胶和药物活性成分。
本发明还提供了如上所述的水凝胶在制备传感器、执行器、晶体管、电容器、服装材料和电池中的用途。
通过上述技术方案，本发明提供了一种粘合性能、机械性能、耐久性能、透明性和透气性更好的水凝胶，并且还具有优良的载药性能和药物缓释性能。这种水凝胶可以为透皮贴片、伤口护理贴片、皮肤护理贴片和组织再生贴片中的至少一种，应用于医药生物、医美、护肤等领域。
本发明的其他特征和优点将在随后的具体实施方式部分予以详细说明。
附图说明
附图是用来提供对本发明的进一步理解，并且构成说明书的一部分，与下面的具体实施方式一起用于解释本发明，但并不构成对本发明的限制。在附图中：
图1描述了用于膜1的试剂混合物的制备步骤。
图2描述了用于膜2的试剂混合物的制备步骤。
图3描述了将反应物混合物引入模具、聚合和获得水凝胶膜的步骤。
图4描述了从模具中取出水凝胶膜的步骤。
图5是水凝胶薄膜1的示例性拉伸照片。
具体实施方式
以下结合附图对本发明的具体实施方式进行详细说明。应当理解的是，此处所描述的具体实施方式仅用于说明和解释本发明，并不用于限制本发明。
本发明第一方面提供了水凝胶，该水凝胶含有水、甘油、纤维素醚和聚合物；所述聚合物包括第一聚合物和第二聚合物；所述第一聚合物为聚丙烯腈，所述第二聚合物为交联的聚丙烯酸或交联的聚N-羟乙基丙烯酰胺。
本发明中，纤维素醚在水凝胶中的作用为包药载体和给药通道同时也作为增粘剂和保水剂；聚丙烯腈和第二聚合物在水凝胶中的作用为增加机械弹力和增加药物溶解性。上述特殊的作用对于本发明的水凝胶粘合性能、机械性能、耐久性能、透明性和透气性更好的可能的原因在于聚丙烯腈和第二聚合物在水凝胶中形成的机械稳定的双网络结构，以及纤维素材料本身的保水和粘连力，使得聚合物拥有粘合性能、机械性能、耐久性能、透明性和透气性。
其中，所述水凝胶的固含量为20-35质量％，优选为22-25质量％。水凝胶的固含量的测定方法可以为将干燥后所得凝胶固体重量除以干燥之前凝胶总重量。
其中，所述纤维素醚与所述聚合物的重量比可以为1：(5-9)；为了进一步提高所述水凝胶的性能，所述纤维素醚与所述聚合物的重量比优选为1：(5-8)。
在一种优选实施方式中，为了满足更好的机械性能的要求，可以将所述水凝胶的组成调整为所述纤维素醚与所述聚合物的重量比为1：(7-9)。
在另一种优选实施方式中，为了满足更好的粘性的要求，可以将所述水凝胶的组成调整为所述纤维素醚与所述聚合物的重量比为1：(5-6)。
其中，所述纤维素可以为甲基纤维素、羟乙基甲基纤维素、羧甲基纤维素、乙基纤维素、苄基纤维素、羟乙基纤维素、羟丙基甲基纤维素、氰乙基纤维素、苄基氰乙基纤维素、羧甲基羟乙基纤维素、苯基纤维素和纳米纤维素中的至少一种。
为了进一步提高所述水凝胶的性能，所述纤维素优选为2-羟乙基纤维素。2-羟乙基纤维素在水凝胶中的作用为增加凝胶粘度同时拥有装药给药功能。上述特殊的作用对于本发明的水凝胶粘合性能、机械性能、耐久性能、透明性和透气性更好的可能的原因在于其取代基团更容易与水键合形成内氢键。。
其中，所述2-羟乙基纤维素的摩尔取代度可以为2-3，优选为2.4-2.6；所述2-羟乙基纤维素的2质量％浓度的水溶液在25℃下的粘度为110-137mPa·S，优选为115-125mPa·S。
其中，可选地，所述聚丙烯腈和所述交联的聚丙烯酸之间的重量比为1：(5-15)，优选为1：(7-12)，更优选为1：(9-11)。
其中，所述聚丙烯腈和交联的聚N-羟乙基丙烯酰胺的重量比为1：(1-20)，优选为1：(2-10)，更优选为1：(3-7)。
其中，所述交联的聚丙烯酸的单体可以包括丙烯酸单体和交联剂单体；所述交联的聚N-羟乙基丙烯酰胺的单体可以包括N-羟乙基丙烯酰胺单体和交联剂单体。
所述交联剂单体可以为二甲基丙烯酸乙二醇酯和聚乙二醇丙烯酸酯中的至少一种，优选为二甲基丙烯酸乙二醇酯。
其中，所述丙烯腈共聚物为光聚合得到的聚合物；所述光聚合所用的光引发剂包括2,2-二甲氧基-2-苯基苯乙酮、安息香、安息香双甲醚、安息香乙醚、安息香异丙醚、安息香丁醚、二苯基乙酮、α,α-二甲氧基-α- 苯基苯乙酮、α,α-二乙氧基苯乙酮、α-羟烷基苯酮、α-胺烷基苯酮、芳酰基膦氧化物、双苯甲酰基苯基氧化膦、二苯甲酮、米蚩酮和过硫酸铵中的至少一种。
所述光聚合所用的光引发剂的使用浓度可以为1-3重量％。
其中，所述水凝胶中，甘油的含量可以为20-40体积％，优选为22-31体积％。
本发明还提供了一种用于制备如上所述的水凝胶的预混物，该预混物含有水、甘油、纤维素醚、丙烯腈单体、丙烯酸单体和交联剂单体；或者，该预混物含有水、甘油、纤维素醚、丙烯腈单体、N-羟乙基丙烯酰胺单体和交联剂单体。
本发明还提供了一种制备水凝胶的方法，该方法包括：将如上所述的预混物与光引发剂混合后进行光固化。
本发明还提供了一种制备水凝胶的方法，该方法包括：
-制备包含2-羟乙基纤维素(4)和水(5)的第一溶液(3)的步骤，
-制备包含光引发剂(7)固化的第二溶液(6)的步骤，
-制备包含丙烯酸(9)或N-羟乙基丙烯酰胺(14)、丙烯腈(10)、二甲基丙烯酸乙二醇酯(11)和甘油(12)的第一混合物(8或15)的步骤，
--所述第一溶液(3)、所述第二溶液(6)和所述第一混合物(8或15)的混合步骤，以获得第二混合物(13或16)，
--用所述第二混合物(13或16)填充模具(23)的步骤，所述第二混合物(13或16)由位于第一疏水材料(140a)中的第一层(140)、位于所述第一层(140)上的位于第二疏水材料(141a)中的第二层(141)和位于所述第二层上的框架(142)组成，所述步骤-用位于所述第三疏水材料(143a)中的第三层(143)封闭所述模具(23)的步骤；
-所述模具(23)的压制步骤，在所述闭合步骤之后，
-所述膜(1或2)的通过光聚合的合成步骤，所述光聚合通过以下步骤 进行；
所述第二混合物(13或16)在经受压力并被所述第三层(143)覆盖的所述模具(23)中用紫外线曝光，以获得包含聚丙烯腈(24)的所述水凝胶膜(1或2)，
-去除所述第三层(143)和所述模具(23)的步骤。
其中，所述第一溶液(3)的制备步骤包括每17毫升和23毫升水(5)溶解0.6克至1.4克的2-羟乙基纤维素(4)，以及在所述相混合之前机械搅拌所述第一溶液(3)持续22小时至26小时的后续阶段。
其中，所述光引发剂(7)包含2，2-二甲氧基-2-苯基苯乙酮(70)。
其中，所述第二溶液(6)的制备步骤包括在所述混合步骤之前，在60分钟至180分钟的时间内，将每体积为1.8毫升至2.2毫升的乙醇(6a)溶解94毫克至106毫克的所述2，2-二甲氧基-2-苯基苯乙酮(70)。
其中，所述第一混合物(8)的所述制备步骤包括按比例添加体积可以在475μL和625μL之间变化的所述丙烯酸(9)和在60μL和210μL之间变化的所述丙烯腈(10)，随后(5)加入一个体积在18μL和25μL之间的所述乙二醇二甲基丙烯酸酯(11)和一个体积在750μL和1200μL之间的所述甘油(12)，并且所述适于获得第二混合物(13)的随后混合步骤包括将体积在1.2mL和3.3mL之间的所述第一溶液(3)加入到体积在1.2mL和3.3mL所述第一混合物(8)中，随后进行持续60分钟和180分钟之间的搅拌机械，并且从随后加入的体积在20μL和180μL之间所述光引发剂(7)。
其中，所述填充步骤包括将0.8毫升至2毫升的所述第二混合物(13)倒入所述模具(23)中，所述框架(142)具有100微米至250微米之间的厚度，并且处于所述称为光聚合的合成阶段通过紫外线照射，在300纳米和380纳米之间的波长下进行，时间在90分钟和150分钟之间变化，强度在75毫瓦/平方厘米和110毫瓦/平方厘米之间变化。
其中，所述框架(142)包含聚二甲基硅氧烷。
其中，所述第一疏水材料(140a)包括有机玻璃，所述第二疏水材料(141a)包括聚四氟乙烯，并且所述第三疏水材料(143a)包括有机玻璃。
其中，所述模具(23)在所述闭合阶段期间也用夹在所述第三层(143)和所述框架(142)之间的包含所述第二疏水材料(141a)的第四层(144)闭合。
本发明还提供了一种药物组合物，该药物组合物还含有如上所述的水凝胶和药物活性成分。
其中，所述药物组合物为透皮贴片、伤口护理贴片、皮肤护理贴片和组织再生贴片中的至少一种，应用于医药生物、医美、护肤等领域。
本发明还提供了如上所述的水凝胶在制备传感器、执行器、晶体管、电容器、服装材料和电池中的用途。
根据本发明特别优选的一种实施方式，制备水凝胶膜(1)的方法包括几个步骤，如图1和图3所示。第一步包括制备包含2-羟乙基纤维素(4)和水(5)的第一溶液(3)。在第一溶液(3)的制备的该阶段中，优选溶解一定量的2-羟乙基纤维素(4)，对于17mL至23mL之间、更优选18mL至21mL之间的每体积水(5)，优选0.6g至1.4g、更优选0.8g至1.2g。然后，在该方法的下一步之前，将前3种溶液进行机械搅拌，时间为22小时至26小时，或更优选23小时至25小时，在该步骤中，将前3种溶液与制备的其它溶液混合。2-羟乙基纤维素(4)意在赋予水凝胶具有受控尺寸的框架结构。2-羟乙基纤维素(4)的这一特征允许水凝胶有利地用于生物医学应用，以逐渐释放药物,同时提供足够的黏附能力和保水能力。
该方法的后续步骤优选包括制备包含聚合光引发剂(7)的第二溶液(6)。需要第二溶液(6)以实现下一步聚合，其有利地由光引发剂(7)活化。光引发剂(7)优选包含2,2-二甲氧基-2-苯基苯乙酮(70)。2,2-二甲氧基-2-苯基苯乙酮(70)特别适合于产生足以聚合该过程中所用单体的较低活性物质。制备第二溶液(6)的该步骤优选包括对于1.8mL至2.2mL或更优选1.9mL至2.1mL之间的每体积乙醇6a溶解94mg至106mg或更优选97mg至 103mg之间的2,2-二甲氧基-2-苯基苯乙酮(70)，时间范围为60分钟至180分钟或更优选在下一混合步骤之前在90分钟和150分钟之间。使用乙醇6a和所示时间提高了2,2-二甲氧基-2-苯基苯乙酮70的稳定性，因为预计会使用该物质进行引发反应。
该方法的下一步包括制备包含丙烯酸(9)、丙烯腈(10)、二甲基丙烯酸乙二醇酯(11)和甘油(12)的第一种混合物(8)。丙烯酸(9)和丙烯腈(10)是将与乙二醇二甲基丙烯酸酯(11)和甘油(12)一起形成最终聚合物结构的单体，其诱导聚合物链的形成。
特别地，制备第一混合物(8)的步骤优选包括按比例添加体积可以在475μL和625μL之间变化或更优选在475μL和550μL之间变化或更优选在480μL和490μL之间变化的丙烯酸(9)和在60μL和210μL之间变化或更优选在150μL和190μL之间变化的丙烯腈(10)，优选随后加入一体积的18μL至25μL或更优选19μL至24μL或更优选19μL至23μL的二甲基丙烯酸乙二醇酯(11)和一体积的750μL至1200μL或更优选850μL至1000μL或更优选900μL至1000μL的甘油12。
该过程的下一阶段包括混合第一种溶液(3)、第二种溶液(6)和第一种混合物(8)，以获得第二种混合物(13)。
混合步骤优选包括向第一混合物(8)中加入体积在1.2毫升至3.3毫升之间，或更优选在1.2毫升至2.5毫升之间，或更优选在1.6毫升至2.5毫升之间的第一溶液3，随后机械搅拌优选60分钟至180分钟，或更优选60分钟至90分钟至150分钟。一旦机械搅拌完成，最后加入一定体积的第二溶液(6)，该体积优选在20μL和130μL之间，或更优选在20μL和60μL之间，或更优选在20μL和40μL之间。
该方法有利地包括用模具(23)的第二混合物13填充的步骤，所述模具14由第一疏水材料140a中的第一层140、位于第一层140上并粘附于其上的第二疏水材料141a中的第二层141、能够执行合成平台功能的第二层 142和位于第二层141上的框架142组成。因此，第一层140是模具的基底，并且优选地由第二层141覆盖，在第二层141上从框架142浇注第二封闭混合物(13)。第一层140由第一疏水材料140a组成，因为第二混合物(13)需要与其接触，所以它不产生结合。
特别地，第一疏水材料140a优选包括有机玻璃，第二疏水材料141a优选包括聚四氟乙烯。这两种材料具有最佳特性，以执行包含第二混合物(13)的功能，同时保持化学惰性要求。这两种材料都可以以薄层的形式使用。第一层140和第二层141优选具有长度优选在10厘米和20厘米之间，更优选在12厘米和18厘米之间的两个表面尺寸。模具(23)的框架142是在第二混合物(13)被注入其中的中心部分中的中空层，并且优选地具有与第一层140和第二层141的横向尺寸相同尺寸的两个横向尺寸。特别地，框架142优选包括聚二甲基硅氧烷。这种材料提供了灵活性、化学惰性和在工艺终止时易于移除。
填充步骤优选地包括在模具(23)中灌注0.8毫升和2毫升之间或更优选1毫升和1.7毫升之间的第二混合物(13)的体积，并且框架142具有100μm和250μm之间或更优选150μm和230μm之间的厚度。模具(21)的填充阶段具有赋予第二混合物(13)产品必须具有的最终形状的功能。一旦第二混合物(13)已经被浇注，用于闭合模具(23)的阶段跟随有由第三疏水材料143a制成的第三层143，第三疏水材料143a优选为有机的和/或在第一疏水材料140a中优选为固体玻璃，能够执行覆盖功能。第三层143被适当地放置，最好是精细地放置在框架142上，框架142包围着存在于其中的混合物(13)。覆盖层具有在随后的合成阶段赋予最终产品正确形状的功能，因此它必须保证与模具(23)的其它部分相同的化学惰性性质。在闭合步骤的一种变型中，模具(23)也用四分之一层144闭合，四分之一层144也包括夹在第三层143和框架142之间的疏水材料，优选PTFE，更优选由第二疏水材料141a组成。
侧向机械支撑、额外的外部上部或下部支撑以及更多支撑可以辅助模具闭合。在模具(23)的闭合步骤之后，接着进行模具的压制步骤。
模具(23)封闭，内含混合物(13)。在该阶段中，对模具(23)的机械压力将优选地在整个随后的合成阶段期间保持。这样，第三层(143)被适当地放置成与混合物(13)紧密接触。在规定使用第四层(144)的程序选择中，后者优选与混合物(13)紧密接触。
下一步骤包括通过光聚合合成所述膜(1)，所述光聚合在第二混合物(13)在模具(23)中经受压力并被第三层(143)覆盖的情况下暴露于紫外线下进行，从而获得由包含聚丙烯腈(24)的水凝胶制成的膜(1)。
如已经预期的那样，聚合通过光引发剂(7)在吸收紫外线辐射后产生的反应性物质进行。因此，聚合过程的效率取决于紫外线辐射水平。因此，优选使用减少的第三厚层(143)，以限制辐射的吸收并允许第二混合物(13)吸收大部分辐射。在提供添加第四层(144)的程序的中，后者也必须具有一个减小的厚度，即优选小于200μm。特别地，在合成阶段，通过照射紫外线进行光聚合的波长优选在300纳米和380纳米之间或更优选在350纳米和370纳米之间，时间范围在90分钟和150分钟之间或更优选在100分钟和135分钟之间或更优选在110分钟和130分钟之间，强度范围在75毫瓦/平方厘米和110毫瓦/平方厘米之间或更优选在85毫瓦/平方厘米和100毫瓦/平方厘米之间。
利用这些参数，光聚合过程允许获得具有期望特性的膜(1)。
在水凝胶膜(1)的合成步骤之后，进行去除第三层(143)和模具(23)的步骤。在移除用于释放水凝胶膜(1)的模具(23)的步骤期间，第二混合物(13)的残余物也被移除，保留在模具(23)内，其在合成阶段期间没有反应。必须去除残留物，因为它会改变薄膜(1)的特性。
为了释放从模具23产生的膜(1)，去除第三层(143)、框架(142)、第二层(141)，最后去除第一层(140)。图4中示出了移除模具(23)的阶段。在该 过程结束时，通过该方法获得水凝胶膜(1)。
根据本发明l特别优选的另外一种实施方式，制备水凝胶膜(2)的方法包括几个步骤，如图2和图3所示。第一步骤包括制备包含2-羟乙基纤维素(4)和水(5)的第一溶液(3)。在第一溶液(3)的制备的该阶段中，优选溶解一定量的2-羟乙基纤维素(4)，对于17mL至23mL之间、更优选18mL至21mL之间的每体积水(5)，优选0.6g至1.4g、更优选0.8g至1.2g。然后，在该方法的下一步之前，将前3种溶液进行机械搅拌，时间为22小时至26小时，或更优选23小时至25小时，在该步骤中，将前3种溶液与制备的其它溶液混合。2-羟乙基纤维素(4)意在赋予水凝胶具有受控尺寸的框架结构。2-羟乙基纤维素(4)的这一特征允许水凝胶有利地用于生物医学应用，以逐渐释放药物，同时提供足够的黏附能力和保水能力。
该方法的后续步骤优选包括制备包含聚合光引发剂(7)的第二溶液(6)。需要第二溶液(6)以实现下一步聚合，其有利地由光引发剂(7)活化。光引发剂(7)优选包含2,2-二甲氧基-2-苯基苯乙酮(70)。2,2-二甲氧基-2-苯基苯乙酮(70)特别适合于产生足以聚合该过程中所用单体的较低活性物质。制备第二溶液(6)的该步骤优选包括在下一混合步骤之前，对于1.8mL至2.2mL或更优选1.9mL至2.1mL之间的每体积乙醇6a，在60分钟至180分钟或更优选90分钟至150分钟的时间段内溶解94mg至106mg或更优选97mg至103mg的2,2-二甲氧基-2-苯基苯乙酮(70)。使用乙醇6a和所示时间提高了2,2-二甲氧基-2-苯基苯乙酮(70)的稳定性，因为预计会使用该物质。
该方法的下一步包括制备包含N-羟乙基丙烯酰胺(14)、丙烯腈(10)、二甲基丙烯酸乙二醇酯(11)和甘油(12)的第一种混合物(15)。N-羟乙基丙烯酰胺(14)和丙烯腈(10)是将与乙二醇二甲基丙烯酸酯(11)和甘油(12)一起形成最终聚合物结构的单体，其诱导聚合物链的形成。
特别地，制备第一混合物(15)的步骤优选包括按比例添加体积可在 700μL和1000μL之间变化或更优选在750μL和950μL之间变化或更优选在720μL和750μL之间变化的N-羟乙基丙烯酰胺(14)和在60μL和210μL之间变化或更优选在150μL和190μL之间变化的丙烯腈(10)，优选随后加入一体积的18μL至25μL或更优选19μL至24μL或更优选20μL至23μL的乙二醇二甲基丙烯酸酯(11)和一体积的750μL至880μL或更优选770μL至850μL或更优选780μL至1200μL的甘油(12)。
该过程的下一阶段包括混合第一种溶液(3)、第二种溶液(6)和第一种混合物(15)，以获得第二种混合物(16)。
混合步骤优选包括向第一混合物(15)中加入体积在1.2毫升至2.3毫升之间，或更优选在1.2毫升至2.5毫升之间，或更优选在1.6毫升至2.5毫升之间的第一溶液(3)，随后机械搅拌优选60分钟至180分钟，或更优选60分钟至90分钟至150分钟。一旦机械搅拌完成，最后加入一定体积的第二溶液(6)，该体积优选在20μL和130μL之间，或更优选在20μL和60μL之间，或更优选在20μL和40μL之间。
该方法有利地包括用模具(23)的第二混合物(16)填充的步骤，该模具(23)由第一疏水材料140a中的第一层140、位于第一层140上并粘附于其上的第二疏水材料141a中的第二层141、能够执行合成平台功能的第二层142和位于第二层141上的框架142组成。因此，第一层140是模具的基底，并且优选地由第二层141覆盖，在第二层141上从框架142浇注第二封闭混合物(16)。第一层140由第一疏水材料140a组成，因为第二混合物(16)需要与其接触，所以它不产生结合。
特别地，第一疏水材料140a优选包括有机玻璃，第二疏水材料141a优选包括聚四氟乙烯。这两种材料具有最佳特性，以执行包含第二混合物(16)的功能，同时保持化学惰性要求。这两种材料都可以以薄层的形式使用。第一层140和第二层141优选具有长度优选在10厘米和20厘米之间，更优选在12厘米和18厘米之间的两个表面尺寸。模具14的框架142是 在第二混合物(16)被注入其中的中心部分中的中空层，并且优选地具有与第一层140和第二层141的横向尺寸相同尺寸的两个横向尺寸。特别地，框架142优选包括聚二甲基硅氧烷。这种材料提供了灵活性、化学惰性和在工艺终止时易于移除。
填充步骤优选地包括在模具(23)中灌注0.8毫升和2毫升之间或更优选1毫升和1.7毫升之间的第二混合物(16)的体积，并且框架142具有100μm和250μm之间或更优选150μm和230μm之间的厚度。模具14的填充阶段具有赋予第二混合物(16)产品必须具有的最终形状的功能。一旦第二混合物(16)已经被浇注，用于闭合模具(23)的阶段跟随有由第三疏水材料143a制成的第三层143，第三疏水材料143a优选为有机的和/或在第一疏水材料140a中优选为固体玻璃，能够执行覆盖功能。第三层143被适当地放置，最好是精细地放置在框架142上，框架142包围着存在于其中的混合物(16)。覆盖层具有在随后的合成阶段赋予最终产品正确形状的功能，因此它必须保证与模具(23)的其它部分相同的化学惰性性质。在闭合步骤的一种变型中，模具(23)也用四分之一层144闭合，四分之一层144也包括夹在第三层143和框架142之间的疏水材料，优选PTFE，更优选由第二疏水材料141a组成。
侧向机械支撑、额外的外部上部或下部支撑以及更多支撑可以辅助模具闭合。在模具(21)的闭合步骤之后，模具(23)的压制步骤跟随在包含混合物(16)的闭合步骤之后。在这个阶段，机械施加到模具(23)的压力，优选在整个随后的合成阶段保持该压力。这样，第三层143被适当地放置成与混合物(16)紧密接触。在规定使用第四层144的程序的变型中，后者优选与混合物(16)紧密接触。
下一步骤包括通过光聚合合成所述膜(2)，所述光聚合在第二混合物(16)在模具(23)中经受压力并被第三层143覆盖的情况下暴露于紫外线下进行，从而获得由包含聚丙烯腈(24)的水凝胶制成的膜(2)。
如已经预期的那样，聚合通过光引发剂(7)在吸收紫外线辐射后产生的反应性物质进行。因此，聚合过程的效率取决于紫外线辐射水平。因此，优选使用减少的第三厚层143，以限制辐射的吸收并允许第二混合物16吸收大部分辐射。在提供添加第四层144的程序的变型中，后者也必须具有一个减小的厚度，即优选小于200μm。特别地，在合成阶段，通过照射紫外线进行光聚合的波长优选在300纳米和380纳米之间或更优选在350纳米和370纳米之间，时间范围在90分钟和150分钟之间或更优选在100分钟和135分钟之间或更优选在110分钟和130分钟之间，强度范围在75毫瓦/平方厘米和110毫瓦/平方厘米之间或更优选在85毫瓦/平方厘米和100毫瓦/平方厘米之间。
利用这些参数，光聚合过程允许获得具有期望特性的膜(2)。
在水凝胶膜(2)的合成步骤之后，进行去除第三层143和模具(23)的步骤。在移除用于释放水凝胶膜(2)的模具(23)的步骤期间，第二混合物(16)的残余物也被移除，保留在模具(23)内，其在合成阶段期间没有反应。必须去除残留物，因为它会改变薄膜(2)的特性。
为了释放从模具(23)产生的膜(2)，去除第三层143、框架142、第二层141，最后去除第一层140。图4中示出了移除模具(23)的阶段。在该过程结束时，通过该方法获得水凝胶膜(2)。
制作膜(1)和膜(2)的方法制作简单。此外，膜(1)和膜(2)由于它们是通过遵循所述程序获得的，因此其具有使它们比现有水凝胶膜更有利的性质。膜(1)和膜(2)比现有的水凝胶膜具有更好的粘合性能，除了那些由羧基和羟基官能团的相互作用产生的特性外，现有的水凝胶膜还源自其特殊的二级结构特性。这种优异的性能可以为有伤口恢复需求的患者带来显著改善的体验(例如：手术后的外科伤口、创伤性伤口和烧伤治疗)和难以处理的部位的医疗应用(例如：关节和四肢)。
膜(1)和膜(2)表现出化学化合物逐渐释放的特性，这种特性可以比现 有薄膜更好地结合到它们的结构中。膜(1)和膜(2)具有更大的释放速度，而随着时间的推移释放效率没有显著降低，这与已知的膜中发生的情况相反。这种特性主要是由于可以根据合成过程的调节方式来调节2-羟乙基纤维素(4)结构的孔径和梯度。这些特性使得膜(1)和膜(2)特别适合于其中需要药剂的逐渐释放效果的应用，例如：透皮贴剂。
事实上，在这类应用中，膜(1)和膜(2)通过其高光学透明度，允许检查与其接触的可能伤口，而无需将其移除。此外，膜(1)和膜(2)具有在暴露于空气的条件下可超过6个月的耐久性。薄膜(1)和薄膜(2)也具有良好的透气性，在膏药等生物医学应用中，这种特性可为细胞增殖创造有利的微环境，提高敷料的有效性。
水凝胶膜(1)和膜(2)的另一个特性在于机械性能，在断裂强度和杨氏模量方面都优于现有膜。该特征使得根据本发明的膜(1)和膜(2)非常有利，因为更好的机械性能将该材料的应用领域扩展到电子器件、组织工程、粘合剂、涂层和可佩戴传感器。具有称为SNIPSy结构的聚丙烯腈或互穿体系的补充网络的存在使得这一优势成为可能。
除此之外，装载化学药剂的能力也将为工业提供潜在的工业应用，如传感器、执行器、晶体管、电容器、服装材料以及作为支撑平台的电池。
本发明可以有落入权利要求所限定的发明概念范围内的变化。
在这种情况下，所有的细节都可以用等同的元素代替，材料、形状和尺寸都可以是任意的。
以下通过实施例进一步详细说明本发明。
实施例1
本实施例用于说明水凝胶膜的制备过程。
制备50mg/mL浓度的2-羟乙基纤维素水溶液。制备50mg/mL浓度的 2,2-二甲氧基-2-苯基苯乙酮的乙醇溶液。制备包含丙烯酸、丙烯腈和二甲基丙烯酸乙二醇酯的单体混合物。
将2-羟乙基纤维素水溶液和单体混合物混合均匀，并调节固含量为23质量％，还加入甘油使得甘油的含量为25体积％，得到聚合前物料，也就是预混物。所述聚合前物料中，2-羟乙基纤维素、丙烯酸、丙烯腈和二甲基丙烯酸乙二醇酯的质量比为125：508：106：19。
将聚合前物料与光引发剂(2,2-二甲氧基-2-苯基苯乙酮的乙醇溶液，使用浓度为2重量％)混合后导入模具中进行光聚合，光聚合的波长为360纳米，时间120分钟，强度90毫瓦/平方厘米，然后去除模具，得到水凝胶薄膜1。
实施例2
按照实施例1的方法进行，不同的是将丙烯酸替换为等质量的N-羟乙基丙烯酰胺；得到水凝胶薄膜2。
对比例1
按照实施例1的方法进行，不同的是将丙烯腈替换为等质量的丙烯酸；得到水凝胶薄膜C1。
对比例2
按照实施例1的方法进行，不同的是将2-羟乙基纤维素替换为等质量的羧甲基纤维素；得到水凝胶薄膜C2。
对比例3
按照实施例1的方法进行，不同的是将丙烯酸替换为等质量的N-异丙基丙烯酰胺；得到水凝胶薄膜C3。
对比例4
按照实施例1的方法进行，不同的是将甘油换为等质量的水；得到水凝胶薄膜C4。
测试实施例1
对实施例1得到的水凝胶薄膜1、实施例2得到的水凝胶薄膜2、对比例1的水凝胶薄膜C1、对比例2得到的水凝胶薄膜C2进行粘合性能、机械性能的测试。结果如表1所示。水凝胶薄膜1的示例性拉伸照片如图5所示。
表1
测试实施例2
对实施例1得到的水凝胶薄膜1、实施例2得到的水凝胶薄膜2、对比例1的水凝胶薄膜C1、对比例2得到的水凝胶薄膜C2进行载药量和药物释放效果的测试，所用药物为利多卡因，结果如表2所示。
表2

根据表1和表2的数据可见，本发明提供了一种粘合性能、机械性能、耐久性能、透明性和透气性更好的水凝胶，并且还具有优良的载药性能和药物缓释性能。
具体地，对比例C3和对比例C4均无法成胶。C2胶体并不稳定，在释放中迅速崩解，无法得到有效数据。其中对比例C4的混合物，在不到10小时的时间就变硬，表明甘油的保水作用极其重要，不仅如此，甘油对胶体的形成也极其重要。另外，从水凝胶薄膜1与对比例C3的对比可以看到，聚丙烯酸对于胶体的三维主体结构至关重要。从水凝胶薄膜1与对比例C1的对比来看，聚丙烯腈能明显降低聚合物机械性能的杨氏常数，能明显减少胶体的在拉伸过程中的回复力，提升机械性能。从水凝胶薄膜1与对比例C2的对比来看，2-羟乙基纤维素是很明显的提升了胶体的粘合度和保水性能。水凝胶薄膜膜1和水凝胶薄膜膜2均可以证明交联的聚N-羟乙基丙烯酰胺和丙烯酸是胶体3D结构的主体。
以上结合附图详细描述了本发明的优选实施方式，但是，本发明并不限于上述实施方式中的具体细节。在本发明的技术构思范围内，可以对本发明的技术方案进行多种简单变型，这些简单变型均属于本发明的保护范围。
另外需要说明的是，在上述具体实施方式中所描述的各个具体技术特征，在不矛盾的情况下，可以通过任何合适的方式进行组合，为了避免不必要的重复，本发明对各种可能的组合方式不再另行说明。
此外，本发明的各种不同的实施方式之间也可以进行任意组合，只要其不违背本发明的思想，其同样应当视为本发明所公开的内容。

Claims (14)

  1. 水凝胶，其特征在于，该水凝胶含有水、甘油、纤维素醚和聚合物；所述聚合物包括第一聚合物和第二聚合物；所述第一聚合物为聚丙烯腈，所述第二聚合物为交联的聚丙烯酸或交联的聚N-羟乙基丙烯酰胺。
  2. 根据权利要求1所述的水凝胶，其中，所述水凝胶的固含量为20-35质量％，优选为22-25质量％；所述纤维素醚与所述聚合物的重量比为1：(5-9)，优选为1：(5-8)。
  3. 根据权利要求1或2所述的水凝胶，其中，所述纤维素醚为甲基纤维素、羟乙基甲基纤维素、乙基纤维素、苄基纤维素、羟乙基纤维素、羟丙基甲基纤维素、氰乙基纤维素、苄基氰乙基纤维素、苯基纤维素和纳米纤维素中的至少一种；
    所述纤维素醚优选为2-羟乙基纤维素。
  4. 根据权利要求3所述的水凝胶，其中，所述2-羟乙基纤维素的摩尔取代度为2-3，优选为2.4-2.6；所述2-羟乙基纤维素的5质量％浓度的水溶液在25℃下的粘度为110-137mPa·S，优选为115-125mPa·S。
  5. 根据权利要求1所述的水凝胶，其中，所述聚丙烯腈和所述交联的聚丙烯酸之间的重量比为1：(5-15)，优选为1：(7-12)，更优选为1：(9-11)；
    所述聚丙烯腈和交联的聚N-羟乙基丙烯酰胺的重量比为1：(1-20)，优选为1：(2-10)，更优选为1：(3-7)。
  6. 根据权利要求1所述的水凝胶，其中，所述交联的聚丙烯酸的单 体包括丙烯酸单体和交联剂单体；所述交联的聚N-羟乙基丙烯酰胺的单体包括N-羟乙基丙烯酰胺单体和交联剂单体；
    所述交联剂单体为二甲基丙烯酸乙二醇酯和聚乙二醇二丙烯酸酯中的至少一种，优选为二甲基丙烯酸乙二醇酯。
  7. 根据权利要求5所述的水凝胶，其中，所述丙烯腈共聚物为光聚合得到的聚合物；所述光聚合所用的光引发剂包括2,2-二甲氧基-2-苯基苯乙酮、安息香、安息香双甲醚、安息香乙醚、安息香异丙醚、安息香丁醚、二苯基乙酮、α,α-二甲氧基-α-苯基苯乙酮、α,α-二乙氧基苯乙酮、α-羟烷基苯酮、α-胺烷基苯酮、芳酰基膦氧化物、双苯甲酰基苯基氧化膦、二苯甲酮、米蚩酮和过硫酸铵中的至少一种；优选所述光聚合所用的光引发剂为2,2-二甲氧基-2-苯基苯乙酮。
  8. 根据权利要求1所述的水凝胶，其中，所述水凝胶中，甘油的含量为20-40体积％，优选为22-31体积％。
  9. 一种用于制备权利要求1-8中任意一项所述的水凝胶的预混物，其特征在于，该预混物含有水、甘油、纤维素醚、丙烯腈单体、丙烯酸单体和交联剂单体；或者，该预混物含有水、甘油、纤维素醚、丙烯腈单体、N-羟乙基丙烯酰胺单体和交联剂单体。
  10. 一种制备水凝胶的方法，其特征在于，该方法包括：将权利要求10所述的预混物与光引发剂混合后进行光固化。
  11. 一种制备水凝胶的方法，其特征在于，该方法包括：
    -制备包含2-羟乙基纤维素(4)和水(5)的第一溶液(3)的步骤，
    -制备包含光引发剂(7)固化的第二溶液(6)的步骤，
    -制备包含丙烯酸(9)或N-羟乙基丙烯酰胺(14)、丙烯腈(10)、二甲基丙烯酸乙二醇酯(11)和甘油(12)的第一混合物(8或15)的步骤，
    --所述第一溶液(3)、所述第二溶液(6)和所述第一混合物(8或15)的混合步骤，以获得第二混合物(13或16)，
    --用所述第二混合物(13或16)填充模具(23)的步骤，所述第二混合物(13或16)由位于第一疏水材料(140a)中的第一层(140)、位于所述第一层(140)上的位于第二疏水材料(141a)中的第二层(141)和位于所述第二层上的框架(142)组成，所述步骤-用位于所述第三疏水材料(143a)中的第三层(143)封闭所述模具(23)的步骤；
    -所述模具(23)的压制步骤，在所述闭合步骤之后，
    -所述膜(1或2)的通过光聚合的合成步骤，所述光聚合通过以下步骤进行；
    所述第二混合物(13或16)在经受压力并被所述第三层(143)覆盖的所述模具(23)中用紫外线曝光，以获得包含聚丙烯腈(24)的所述水凝胶膜(1或2)，
    -去除所述第三层(143)和所述模具(23)的步骤。
  12. 一种药物组合物，其特征在于，该药物组合物含有权利要求1-8中任意一项所述的水凝胶和药物活性成分。
  13. 根据权利要求12所述的药物组合物，其中，所述药物组合物为透皮贴片、伤口护理贴片、皮肤护理贴片和组织再生贴片中的至少一种。
  14. 权利要求1-8中任意一项所述的水凝胶在制备传感器、执行器、晶体管、电容器、服装材料和电池中的用途。
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