Hydrogel precursor liquid, method for producing hydrogel manufactured product, and hydrogel manufactured product

Abstract

The hydrogel precursor fluid comprises water and a 1 CH=CR 2 A compound represented by X or a salt thereof, wherein X represents a carboxyl group or an ester thereof, a sulfo group or an ester thereof, and R 1 and R 2 Each independently represents a hydrogen atom, an alkyl group, an aryl group, a carboxyl group, or an alkylcarboxyl group.

Description

Technical Field

[0001] The invention relates to a hydrogel precursor liquid, a method for producing a hydrogel product and a hydrogel product. Background Art

[0002] As 3D modeling technology has made significant progress, various 3D printers such as fused deposition modeling, binder jetting, photomodeling, powder sintering and stacking modeling, and material jetting have been used in the manufacturing industry. In addition, corresponding modeling applications for various materials including metals and resins have been proposed, and it is expected that they can be applied not only to industry but also to the medical / health care field.

[0003] This is because 3D data can be easily obtained from 3D scanners, CT, MRI images, etc., and by using 3D printers, three-dimensional manufactured products that match individual characteristics can be precisely produced.

[0004] As an example of the application of 3D printers in the medical and health fields, in the health field, it is used for hearing aids and prostheses that need to reflect the unique shapes of each person. In addition, in the field of biomedical engineering, research on the modeling of artificial bones that can be implanted with titanium, hydroxyapatite, PEEK, etc. and artificial organs formed by direct cell stacking is also being actively carried out. In addition, in the medical field, for the practice and simulation of surgery, manufacturing products that can simulate the shape of real organs for medical professionals to practice skills are also being gradually promoted. In recent years, the development of medical devices has made progress. Compared with the previous medical methods of large-area incision and resection, minimally invasive medical treatment that reduces the burden on patients through catheter / endoscope / robot assistance is gradually becoming the mainstream. On the other hand, surgical operations using these medical devices require very advanced technology and proficiency. From the perspective of preventing medical accidents, the importance of providing medical professionals with appropriate manufacturing products for practicing skills has been recognized. In addition, in difficult operations with few historical cases, if a manufacturing product for medical professionals to practice skills that can reproduce the details of the target part can be obtained in advance, detailed preoperative simulation can be performed.

[0005] These manufactured products for medical professionals to practice skills can use acrylic or polyurethane resin products made by 3D printers, or silicone products made by mold injection. However, when using these methods, the resin is too hard and therefore cannot be used for actual skill practice such as suturing and incision.

[0006] In addition, although hydrogels derived from natural foods such as Japanese gelatin and rubbery traditional food konjac can be used for energy devices, there are problems such as difficulty in arbitrary three-dimensional shaping and very weak strength, making it impossible to reproduce the feeling of cutting and suturing operations.

[0007] In order to solve the above problems, for example, Non-Patent Document 1 discloses a high-water-content and tough hydrogel prepared using sodium polyacrylate, clay, water, and a double-terminal dendrimer compound.

[0008] Citation List

[0009] Non-patent literature

[0010] [Non-patent document 1] Wang et al., Nature, Vol. 463, January 21, 2010 Summary of the invention

[0011] Technical issues

[0012] The object of the present invention is to provide a hydrogel precursor liquid having a certain degree of compression stress and a fracture limit, and capable of producing a hydrogel product that can be cut by an energy device such as an electrosurgeon.

[0013] Solutions to the problem

[0014] In order to solve the above problems, the hydrogel precursor solution of the present invention contains a compound represented by the following Chemical Formula 1 and water.

[0015] R1CH=CR2X (chemical formula 1)

[0016] Here, X represents a carboxyl group or an ester thereof, a sulfo group or an ester thereof, and R1 and R2 each independently represent a hydrogen atom, an alkyl group, an aryl group, a carboxyl group, or an alkylcarboxyl group.

[0017] Effects of the Invention

[0018] According to the present invention, a hydrogel precursor solution can be provided that can produce a hydrogel product having a certain degree of compression stress and a fracture limit and can cope with operations such as incision and suturing by an energy device such as an electrosurgeon. DETAILED DESCRIPTION

[0019] The present invention is described below with reference to Examples. One aspect of the hydrogel precursor fluid of the present invention is the following (1), which includes (2) to (10).

[0020] (1) The hydrogel precursor liquid contains the compound represented by Chemical Formula 1 or a salt thereof, and water.

[0021] R1CH=CR2X (chemical formula 1)

[0022] Here, X represents a carboxyl group or an ester thereof, a sulfo group or an ester thereof, and R1 and R2 each independently represent a hydrogen atom, an alkyl group, an aryl group, a carboxyl group, or an alkylcarboxyl group.

[0023] (2) The hydrogel precursor liquid according to the above (1) further comprises a polymerizable monomer.

[0024] (3) The hydrogel precursor solution according to (1) or (2) above further comprises a mineral dispersible in water.

[0025] (4) The hydrogel precursor solution according to any one of (1) to (3) above further comprises vinyl silane.

[0026] (5) The hydrogel precursor solution according to any one of (1) to (4) above is used for producing a hydrogel product.

[0027] (6) A method for manufacturing a hydrogel product, comprising: forming a hydrogel precursor liquid film using the hydrogel precursor liquid described in any one of (1) to (4) above; curing the hydrogel precursor liquid film to form a layer; and repeating the forming and curing steps to stack the layers.

[0028] (7) The method according to (6) above, wherein the liquid film is formed by inkjet printing.

[0029] (8) A method for manufacturing a hydrogel product, comprising: exposing the hydrogel precursor liquid described in any one of (1) to (5) above to light, curing the hydrogel precursor liquid to form a layer; and repeating the exposure to sequentially form and stack the layers to manufacture the hydrogel product.

[0030] (9) A method for manufacturing a hydrogel product, comprising: injecting the hydrogel precursor liquid described in any one of (1) to (5) above into a mold; curing the hydrogel precursor liquid; and removing the mold.

[0031] (10) A hydrogel manufactured product comprising a hydrogel formed by curing the hydrogel precursor liquid described in any one of (1) to (5) above.

[0032] Hydrogel precursor solution

[0033] The hydrogel precursor liquid of the present invention contains the compound represented by Chemical Formula 1 or a salt thereof, and water, and may further contain other optional components as required.

[0034] R1CH=CR2X (chemical formula 1)

[0035] Here, X represents a carboxyl group or an ester thereof, a sulfo group or an ester thereof, and R1 and R2 each independently represent a hydrogen atom, an alkyl group, an aryl group, a carboxyl group, or an alkylcarboxyl group.

[0036] Thus, it is possible to produce a hydrogel manufactured product that has a certain degree of compression stress and fracture limit and can be cut by an energy device such as an electrosurgeon. In addition, since the hydrogel precursor of the present invention can be prepared with a particularly low viscosity, it is suitable for use in a liquid for producing a three-dimensional manufactured product, preferably a liquid for producing a three-dimensional manufactured product produced by an additive molding method, particularly an ink composition for a three-dimensional molding device using a discharge head such as an inkjet head of an inkjet method.

[0037] The compound represented by chemical formula 1

[0038] The compound contained in the hydrogel precursor liquid of the present invention is represented by the following chemical formula 1:

[0039] R1CH=CR2X (chemical formula 1)

[0040] In chemical formula 1, X represents -COOA or -SO2A, where A represents a hydrogen atom, an alkyl group, an aryl group, or an alkyl hydroxyl group, or a carboxylate thereof. The compound forms its main chain when polymerized by active energy ray irradiation or the like. R1 and R2 independently represent a hydrogen atom, an alkyl group, an aryl group, a carboxyl group, or an alkyl carboxyl group. In the present invention, a hydrocarbon group or an alkyl group refers to a straight chain or branched hydrocarbon group, preferably a hydrocarbon group having a maximum of 6 carbon atoms. In the present invention, an aromatic hydrocarbon group or an aromatic hydrocarbon group refers to an aromatic hydrocarbon group which may be a monocyclic or condensed ring, preferably an aromatic hydrocarbon group having a maximum of 6 carbon atoms.

[0041] The chemical represented by Chemical Formula 1 or a salt thereof is not particularly limited and may be appropriately selected according to the purpose, and preferably contains at least one metal salt of (meth)acrylic acid from the viewpoint of obtaining a manufactured product having excellent breaking stress and elongation.

[0042] Examples of the compound represented by the above chemical formula 1 include, but are not limited to, unsaturated monocarboxylic acids such as acrylic acid, methacrylic acid, and crotonic acid; monoalkyl esters of unsaturated dicarboxylic acids such as itaconic acid, maleic acid, maleic anhydride, fumaric acid, maleic acid monoalkyl esters, fumaric acid monoalkyl esters, and itaconic acid monoalkyl esters; unsaturated dicarboxylic acids such as citraconic acid; unsaturated monomers containing a phosphoric acid group such as ethyl (meth)acrylate acid phosphate, polyethylene glycol mono(meth)acrylate acid phosphate, and polypropylene glycol mono(meth)acrylate acid phosphate; 2-(meth)acryloyloxyethyl succinic acid, β-carboxyethyl (meth)acrylate, monohydroxyethyl (meth)acrylate phthalate, (meth)acryloyloxyethyl succinic acid, 2-acrylic acid, ethylenesulfonic acid, (meth)acryloylphosphonic acid, 2-(meth)acrylic acid

[0063] The invention also includes 2-(meth)acrylamide-2-methylpropanesulfonic acid, α-methylstyrenesulfonic acid, 2-(meth)acryloxyethyl phthalic acid, 3-(2-carboxyethoxy)-3-oxypropyl ester, 2-(meth)acryloxyethyl tetrahydrophthalic acid, 2-(meth)acryloxyethyl hexahydrophthalic acid, ω-carboxy polycaprolactone (n=2) mono(meth)acrylate, glycerol mono(meth)acrylate, hydroxymethyl (meth)acrylate, hydroxyethyl (meth)acrylate, hydroxypropyl (meth)acrylate, hydroxybutyl (meth)acrylate, hydroxypentyl (meth)acrylate, hydroxyhexyl (meth)acrylate, hydroxyethyl vinyl ether, diethylene glycol monovinyl ether, hydroxybutyl vinyl ether, polypropylene glycol mono(meth)acrylate, polyethylene glycol mono(meth)acrylate, hydroxyethyl acrylamide, and the like.

[0043] Examples of the metal salt of (meth)acrylic acid include potassium acrylate, zinc acrylate, potassium methacrylate, magnesium acrylate, calcium acrylate, zinc methacrylate, magnesium methacrylate, aluminum acrylate, neodymium methacrylate, sodium methacrylate, and sodium acrylate.

[0044] These may be used alone or in combination.

[0045] Polymerizable monomer

[0046] In addition to the compound represented by the above chemical formula 1, a polymerizable monomer may be added to the above hydrogel precursor liquid. The "polymerizable monomer" of the present invention forms a random copolymer with the compound represented by the above chemical formula 1, thereby improving the strength of the hydrogel manufactured product, so that the model used for surgical operations for medical personnel has mechanical properties similar to real organs.

[0047] As the polymerizable monomer, a monofunctional monomer and a polyfunctional monomer can be used.

[0048] Monofunctional monomer

[0049] Examples of the monofunctional monomer include, but are not limited to, (meth)acrylamide derivatives such as acrylamide, methacrylamide, N-substituted acrylamide derivatives, N,N-disubstituted acrylamide derivatives, N-substituted methacrylamide derivatives, N,N-disubstituted methacrylamide derivatives, and other monofunctional monomers. These may be used alone or in combination.

[0050] Examples of (meth)acrylamide derivatives include, but are not limited to, N,N-dimethylacrylamide, N-isopropylacrylamide, N-hydroxymethylacrylamide, acryloylmorpholine, dimethylmethacrylamide, N-isopropylmethacrylamide, N-hydroxymethylmethacrylamide, and methacryloylmorpholine. These can be used alone or in combination. Among them, acryloylmorpholine and N,N-dimethylacrylamide are preferred from the perspective of polymerization stability.

[0051] Examples of other monofunctional monomers include, but are not limited to, acrylates, alkyl acrylates, methacrylates, and alkyl methacrylates.

[0052] Examples of acrylic acid esters include, but are not limited to, hydroxyethyl acrylate, hydroxypropyl acrylate, dimethylaminoethyl acrylate, dimethylaminopropyl acrylate, and alkyl acrylates.

[0053] Examples of the alkyl acrylate include methyl acrylate, ethyl acrylate, butyl acrylate, 2-ethylhexyl acrylate, and lauryl acrylate.

[0054] Examples of methacrylates include, but are not limited to, hydroxyethyl methacrylate, hydroxypropyl methacrylate, dimethylaminoethyl methacrylate, dimethylaminopropyl methacrylate, and alkyl methacrylates.

[0055] Examples of the alkyl methacrylate include, but are not limited to, methyl methacrylate, ethyl methacrylate, butyl methacrylate, lauryl methacrylate, octadecyl methacrylate, and glycidyl methacrylate.

[0056] Examples of other monofunctional monomers include, but are not limited to, 2-ethylhexyl (meth)acrylate (EHA), 2-hydroxyethyl (meth)acrylate (HEA), 2-hydroxypropyl (meth)acrylate (HPA), caprolactone-modified tetrahydro (meth)acrylate tetrahydrofurfuryl, isobornyl (meth)acrylate, 3-methoxybutyl (meth)acrylate, tetrahydrofurfuryl (meth)acrylate, lauryl (meth)acrylate, 2-phenoxyethyl (meth)acrylate, isodecyl (meth)acrylate, isooctyl (meth)acrylate, tridecyl (meth)acrylate, caprolactone (meth)acrylate, and ethoxylated nonylphenol (meth)acrylate. These may be used alone or in combination.

[0057] Multifunctional monomers

[0058] Examples of the polyfunctional monomer include difunctional monomers and trifunctional or higher-functional monomers.

[0059] The multifunctional monomer functions as a cross-linking agent that cross-links random copolymer molecules formed of the compound represented by the above Chemical Formula 1 and the polymerizable monomer.

[0060] Examples of the bifunctional monomer include, but are not limited to, tripropylene glycol di(meth)acrylate, triethylene glycol di(meth)acrylate, tetraethylene glycol di(meth)acrylate, polypropylene glycol di(meth)acrylate, neopentyl glycol hydroxypivalate di(meth)acrylate (MANDA), hydroxypivalate neopentyl glycol di(meth)acrylate (HPNDA), 1,3-butylene glycol di(meth)acrylate (BGDA), 1,4-butanediol di(meth)acrylate (BUDA), 1,6-hexanediol di(meth)acrylate (BGDA), 1,4-butanediol di(meth)acrylate (BUDA), 1,6-hexanediol di(meth)acrylate (BGDA), 1,4-butanediol di(meth)acrylate (BUDA), 1,6-hexanediol di(meth)acrylate (BGDA), 1,4-hex ... Acrylate (HDDA), 1,9-nonanediol di(meth)acrylate, diethylene glycol di(meth)acrylate (DEGDA), neopentyl glycol di(meth)acrylate (NPGDA), tripropylene glycol di(meth)acrylate (TPGDA), caprolactone-modified hydroxypivalate neopentyl glycol di(meth)acrylate, propoxylated pentylene glycol di(meth)acrylate, ethoxy-modified bisphenol A di(meth)acrylate, polyethylene glycol 200 di(meth)acrylate, polyethylene glycol 400 di(meth)acrylate. These may be used alone or in combination.

[0061] Examples of trifunctional or higher functional monomers include, but are not limited to, trimethylolpropane tri(meth)acrylate (TMPTA), pentaerythritol tri(meth)acrylate (PETA), dipentaerythritol hexa(meth)acrylate (DPHA), triallyl isocyanate, (meth)acrylate of ε-caprolactone-modified dipentaerythritol, tri(2-hydroxyethyl)isocyanurate tri(meth)acrylate, ethoxylated trimethylolpropane tri(meth)acrylate, propoxylated trimethylolpropane tri(meth)acrylate, propoxylated glycerol tri(meth)acrylate, pentaerythritol tetra(meth)acrylate, ditrimethylolpropane tetra(meth)acrylate, dipentaerythritol hydroxypenta(meth)acrylate, ethoxylated pentaerythritol tetra(meth)acrylate, penta(meth)acrylate. These may be used alone or in combination.

[0062] The content of the polymerizable monomer is preferably 0.5 to 30% by mass relative to the total amount of the hydrogel precursor solution. If the content of the polymerizable monomer is too high, the cutting performance of the electrosurgical knife will deteriorate. It is preferably 0.5 to 10% by mass.

[0063] Water dispersible minerals

[0064] The hydrogel precursor liquid may further contain a water-dispersible mineral in addition to the compound represented by Chemical Formula 1. Thus, the strength of the hydrogel product is increased, so that the model used for surgical operations for medical personnel has mechanical properties similar to those of real organs.

[0065] The water-dispersible mineral is not particularly limited and may be appropriately selected depending on the intended purpose. For example, layered minerals are suitable.

[0066] As the layered mineral, a layered mineral dispersed in water in a monolayer state is preferred.

[0067] The layered mineral is not particularly limited and may be appropriately selected depending on the intended purpose. For example, a water-swellable layered clay mineral is suitable.

[0068] Examples of the water-swellable layered clay mineral include water-swellable smectite and water-swellable mica.

[0069] More specifically, it includes, but is not limited to, water-swellable hectorite, water-swellable montmorillonite, water-swellable saponite, and water-swellable synthetic mica containing sodium as an interlayer ion.

[0070] The water-swellability mentioned above means that water molecules are inserted between the layers of the layered mineral, making it possible to disperse in water.

[0071] The water-swellable layered clay minerals mentioned above may be used alone or in combination, and may be appropriately synthesized minerals or commercially available products.

[0072] Examples of the commercially available products include, but are not limited to, synthetic hectorite (LAPONITE XLG, manufactured by RockWood Additions Ltd), SWN (manufactured by Coop Chemical Ltd), and hectorite fluoride SWF (manufactured by Coop Chemical Ltd). Among them, synthetic hectorite is preferred.

[0073] The content of the water-dispersible mineral is preferably 1 to 40% by mass, more preferably 1 to 15% by mass, based on the total amount of the liquid composition.

[0074] Vinyl silane

[0075] The hydrogel precursor liquid may further contain vinyl silane in addition to the compound represented by Chemical Formula 1. Thus, the strength of the hydrogel product is increased, so that the model used for surgical operations for medical personnel has mechanical properties similar to those of real organs.

[0076] Examples of vinyl silanes include, but are not limited to, (1-bromovinyl)trimethylsilane, 1,4-bis(dimethylvinylsilyl)benzene, chlorodimethylvinylsilane, chloro(methyl)(phenyl)(vinyl)silane, dichloromethylvinylsilane, diethoxymethylvinylsilane, 2-(dimethylvinylsilyl)pyridine, dimethoxymethylvinylsilane, dimethyldivinylsilane, 3-[[dimethyl(vinyl)silyl]oxy]-1,1,5,5-tetramethyl-3-phenyl-1,5-divinyltrisiloxane, 1,3-dimethyl-1,3-diphenyl-1,3-divinyl Disiloxane, dimethylphenylvinylsilane, octavinyloctasilsesquioxane, triphenylvinylsilane, triethylvinylsilane, 2,4,6,8-tetramethyl-2,4,6,8-tetravinylcyclotetrasiloxane, 2,4,6-trimethyl-2,4,6-trivinylcyclotrisilazane, trimethylsilyl ketone ethyl trimethylsilyl acetal (mixture of isomers), (E)-trimethyl (3,3,3-trifluoro-1-propenyl) silane, tetrakis [dimethyl (vinyl) silyl] orthosilicate, 2,4,6-trimethyl-2,4,6-trivinylcyclotrisiloxane, vinyl trimethylsilane.

[0077] The content of the vinylsilane is preferably 0.01 to 5% by mass, more preferably 0.01 to 1% by mass, based on the total amount of the liquid composition.

[0078] Solvents

[0079] Preferably water is used as the main solvent. Solid free-form articles can be made using this main solvent as a hydrogel.

[0080] Water may be mixed with an organic solvent that is soluble in water.

[0081] The content of the solvent is preferably 10% by mass or more, more preferably 60% by mass or more, and preferably 90% by mass or less, more preferably 80% by mass or less, relative to the total amount of the hydrogel precursor liquid.

[0082] Water was used as the main solvent for the hydrogel.

[0083] The water is not particularly limited and may be appropriately selected depending on the purpose. For example, pure water or ultrapure water such as ion-exchanged water, ultrafiltered water, reverse osmosis water, and distilled water is suitable.

[0084] The water may be used to dissolve or disperse other components such as an organic solvent, depending on the purpose of imparting moisturizing properties, antibacterial properties, conductivity, adjusting hardness, etc.

[0085] Other Ingredients

[0086] There are no particular restrictions on other ingredients, and they may be appropriately selected according to the purpose, such as stabilizers, surface treatment agents, polymerization initiators, colorants, viscosity modifiers, tackifiers, antioxidants, anti-aging agents, crosslinking accelerators, ultraviolet absorbers, plasticizers, preservatives, and dispersants.

[0087] Stabilizer

[0088] To stabilize the properties as a liquid, a stabilizer may be used as needed, such as high concentration phosphates, glycols, and nonionic surfactants.

[0089] Surface treatment agent

[0090] Examples of the surface treatment agent include, but are not limited to, polyester resins, polyvinyl acetate resins, silicone resins, oxoindene resins, fatty acid esters, glycerol esters, and waxes.

[0091] Polymerization initiator

[0092] Examples of the polymerization initiator include, but are not limited to, thermal polymerization initiators and photopolymerization initiators. Photopolymerization initiators are used in stereolithography, and both photopolymerization initiators and thermal polymerization initiators are used in casting.

[0093] As the photopolymerization initiator, any material that generates radicals when irradiated with light (ultraviolet rays having a wavelength range of 220 to 500 nm) can be used. Examples of such photopolymerization initiators include, but are not limited to, acetophenone, 2,2-diethoxyacetophenone, p-dimethylaminoacetophenone, benzophenone, 2-chlorobenzophenone, p,p'-dichlorobenzophenone, p,p-bisdiethylaminobenzophenone, Michel ketone, dibenzoyl, benzoin, benzoin methyl ether, benzoin ethyl ether, benzoin isopropyl ether, benzoin n-propyl ether, benzoin isobutyl ether, benzoin n-butyl ether, benzyl methyl ketal, thioxanthone, 2-chlorothioxanthone, 2-hydroxy-2-methyl-1-phenyl-1-one, 1-(4-isopropylphenyl)2-hydroxy-2-methylpropane-1-one, methyl benzoylformate, 1-hydroxycyclohexylphenyl ketone, azobisisobutyronitrile, benzoyl peroxide, and di-tert-butyl peroxide. These may be used alone or in combination.

[0094] The thermal polymerization initiator is not particularly limited and may be appropriately selected depending on the intended purpose. For example, an azo initiator, a peroxide initiator, a persulfate initiator, or a redox initiator may be used.

[0095] As the azo initiator, a commercially available product can be used.

[0096] Commercially available products include, but are not limited to, VA-044, VA-46B, V-50, VA-057, VA-061, VA-067, VA-086, 2,2'-azobis(4-methoxy-2,4-dimethylvaleronitrile) (VAZO 33), 2,2'-azobis(2-amidinopropane) dihydrochloride (VAZO 50), 2,2'-azobis(2,4-dimethylvaleronitrile) (VAZO 52), 2,2'-azobis(isobutyronitrile) (VAZO 64), 2,2'-azobis-2-methylbutyronitrile (VAZO 65), 2,2'-azobis(2-methylbutyronitrile) (VAZO 66), 2,2'-azobis(2-methylbutyronitrile) (VAZO 67), 2,2'-azobis(2-methylbutyronitrile) (VAZO 68), 2,2'-azobis(2-methylbutyronitrile) (VAZO 69), 2,2'-azobis(2-methylbutyronitrile) (VAZO 70), 2,2'-azobis(2-methylbutyronitrile) (VAZO 71), 2,2'-azobis(2-methylbutyronitrile) (VAZO 72), 2,2'-azobis(2-methylbutyronitrile) (VAZO 73), 2,2'-azobis(2-methylbutyronitrile) (VAZO 74), 2,2'-azobis(2-methylbutyronitrile) (VAZO 75), 2,2'-azobis(2-methylbutyronitrile) (VAZO 67), 1,1-azobis(1-cyclohexanecarbonitrile) (VAZO88) (all available from DuPont Chemical Company, "VAZO" is a trademark), 2,2'-azobis(2-cyclopropylpropionitrile), 2,2'-azobis(methyl isobutyrate) (V-601) (all available from Fuji Film Co., Ltd. and Wako Pure Chemical Industries, Ltd.).

[0097] Examples of peroxide initiators include, but are not limited to, benzoyl peroxide, acetyl peroxide, lauroyl peroxide, decanoyl peroxide, dihexadecyl peroxide, bis(4-tert-butylcyclohexyl)peroxydicarbonate (Perkadox 165) (both available from Akzo Noble NV, "Perkadox" is a trademark), di(2-ethylhexyl)peroxydicarbonate, tert-butyl peroxypivalate (Lupersol 11) (both available from Elf Atochem SA, "Lupersol" is a trademark), tert-butyl peroxy(2-ethylhexanoate) (Trigonox 21-C50) (available from Akzo Nobel NV, "Trigonox" is a trademark), diisopropylbenzene peroxide, and the like.

[0098] Examples of persulfate initiators include, but are not limited to, potassium persulfate, sodium persulfate, and ammonium persulfate.

[0099] Examples of redox initiators include, but are not limited to, a combination of a persulfate initiator and a reducing agent such as sodium metabisulfite or sodium bisulfite, a system based on an organic peroxide and a tertiary amine group (e.g., a system based on benzoyl peroxide and dimethylaniline), and a system based on an organic hydroperoxide and a transition metal (e.g., a system based on cumene hydroperoxide and cobalt naphthoate).

[0100] Pigments

[0101] Examples of the coloring material include various pigments and dyes that can impart black, white, magenta, cyan, yellow, green, orange, and lustrous colors such as gold and silver.

[0102] As the pigment, an inorganic pigment or an organic pigment can be used, and they can be used alone or in combination.

[0103] Examples of inorganic pigments include, but are not limited to, carbon black such as furnace black, lamp black, acetylene black, channel black (CI Pigment Black 7), iron oxide, and titanium oxide.

[0104] Examples of organic pigments include, but are not limited to, azo pigments such as insoluble azo pigments, condensed azo pigments, azo lakes, chelated azo pigments, phthalocyanine pigments, perylene and pyrene pigments, anthraquinone pigments, quinacridone pigments, dioxane pigments, thioindigo pigments, isoindolinone pigments, polycyclic pigments such as quinophthalone pigments, dye chelates (e.g., basic dye type chelates, acid dye type chelates, etc.), dye lakes (e.g., basic dye type lakes, acid dye type lakes, etc.), nitro pigments, nitroso pigments, aniline black, daylight fluorescent pigments, and the like.

[0105] In order to improve the dispersibility of the pigment, a dispersant may be further contained. The dispersant is not particularly limited, and for example, a dispersant generally used for preparing a pigment dispersion, such as a polymer dispersant, may be used.

[0106] The dyes include, for example, acid dyes, direct dyes, reactive dyes, basic dyes, and combinations thereof.

[0107] When color materials are used in material jetting, full-color manufacturing products can be produced using a variety of colors such as black, cyan, magenta, yellow, and white.

[0108] The content of the colorant is not particularly limited and can be appropriately determined according to the desired color concentration, dispersibility in the hydrogel precursor solution, etc., but is preferably 0.1 to 20% by mass relative to the total amount of the hydrogel precursor solution.

[0109] The hydrogel precursor liquid of the present invention can be prepared using the above-mentioned various components, and its preparation means and conditions are not particularly limited. For example, the compound represented by Chemical Formula 1, water, polymerizable monomers and other components are put into a disperser such as a ball mill, a small mill, a disc mill, a pin mill, a sand mill, etc., and prepared by mixing.

[0110] Viscosity

[0111] The viscosity of the hydrogel precursor liquid is not particularly limited.

[0112] When the hydrogel precursor liquid is used in the material jetting method, it is preferred that the viscosity be 3 to 60 mPa·s at 25°C, more preferably 6 to 30 mPa·s. When the viscosity is lower than 3 mPa·s, the discharge is unstable, so that the liquid is not discharged in a straight line, or is not discharged during the manufacturing process, and when it exceeds 40 mPa·s, it may not be ejected. In addition, the viscosity of the contained hydrogel precursor liquid can be adjusted to a desired value by changing the temperature of the nozzle.

[0113] When a hydrogel precursor liquid is used in stereolithography, the viscosity at 25°C is preferably 50 mPa·s or more, more preferably 100 mPa·s or more, and most preferably 200 mPa·s or more from the perspective of maintaining the stability of the solidified material in the molding tank. From the perspective of easy operation, the viscosity is preferably 20,000 mPa·s or less, more preferably 15,000 mPa·s or less, and most preferably 12,000 mPa·s or less.

[0114] In addition, the viscosity of the contained hydrogel precursor liquid can be adjusted to a desired value by changing the temperature of the molding tank.

[0115] When the hydrogel precursor liquid is used in the mold forming method, it preferably has a viscosity of 3 to 1000 mPa·s at 25°C, more preferably 3 to 100 mPa·s or less. If the viscosity exceeds 1000 mPa·s, the handling performance of the hydrogel precursor liquid is reduced due to the high viscosity.

[0116] The viscosity can be measured, for example, using a rotational viscometer (VISCOMATE VM-150III, manufactured by Toki Sangyo Co., Ltd.) in an environment of 25° C. The viscosity can be adjusted by, for example, mixing a monomer, a mineral dispersed in a solvent, or solvents of different viscosities.

[0117] Method for preparing hydrogel manufacturing products

[0118] As a method for preparing a hydrogel product using the hydrogel precursor solution of the present invention, the hydrogel product can be produced by the methods described in the following first to third aspects.

[0119] Preparation method of the first form

[0120] The method for preparing a hydrogel manufacturing product comprises: forming a liquid film of a hydrogel precursor liquid; curing the liquid film to form a layer; and repeating the forming and curing steps to stack the layers. The method may further include other steps. The above-mentioned liquid film forming step is preferably implemented by inkjet printing, which is generally called material jetting.

[0121] The preparation method of the first form of hydrogel manufacturing product can simultaneously shape the color ink and other resin materials by increasing the number of nozzles, so it can cope with the mixed shaping of color shaping and resin components.

[0122] In the first embodiment of the method for preparing a hydrogel product, the above steps are repeated multiple times. The number of repetitions varies depending on the size, shape, structure, etc. of the three-dimensional product to be produced, and cannot be generalized, but if the thickness of each layer is within the range of 10 μm to 50 μm, high-precision and non-peeling molding can be performed, so it is preferred to repeat the stacking until the height of the hydrogel product to be produced is just right.

[0123] Liquid film forming process and liquid film forming device

[0124] The liquid film forming step is a step of applying a hydrogel precursor liquid containing the compound represented by Chemical Formula 1 and water to form a liquid film containing the hydrogel precursor liquid, and is achieved by a liquid film forming apparatus.

[0125] In order to impart strength to the hydrogel precursor liquid, it is preferred to contain a polymerizable monomer or a mineral or vinyl silane dispersible in water.

[0126] The liquid film forming apparatus is not particularly limited and can be appropriately selected according to the purpose, and for example, a spray method, an inkjet printing method, a dispenser method, etc. can be used. In order to implement these methods, a known apparatus can be suitably used.

[0127] Among them, the above-mentioned dispenser method has excellent droplet quantification, but the coating area is narrow, and the above-mentioned spray method easily forms fine sprays, has a large coating area, and excellent coating properties, but the droplet quantification is poor, and the droplets scatter due to the spray flow. Therefore, in the present invention, the above-mentioned inkjet printing method is particularly preferred. Compared with the above-mentioned spray method, the above-mentioned inkjet printing method has good droplet quantification, and compared with the above-mentioned dispenser method, the advantage is that the coating area is large, and a complex three-dimensional shape can be formed and obtained with high precision and efficiency, so it is preferred.

[0128] A commercially available inkjet stereolithography printer can be used. An example of a commercially available inkjet printing device is AGILISTA (manufactured by KEYENCE Corporation).

[0129] Preparation method of the second form

[0130] The second aspect of the preparation method is stereolithography.

[0131] The stereolithography method is characterized in that the hydrogel manufacturing product is prepared by exposing the hydrogel precursor liquid layer by layer, curing and laminating in sequence.

[0132] Each layer of the laminate is obtained by irradiating the surface of the hydrogel precursor liquid with light. In addition, the liquid surface can be smoothed by, for example, a recoater. At this time, by selectively irradiating light, a cured product (cross-sectional cured layer) having a cross section of a desired pattern can be obtained.

[0133] The manufacturing method of the second form of the hydrogel manufacturing product of the present invention is to form a solidified product (cross-sectional solidified layer) of the hydrogel precursor liquid by exposing the liquid surface of the hydrogel precursor liquid, and then re-supply the hydrogel precursor liquid on the solidified product (cross-sectional solidified layer) and expose it to form a solidified product (cross-sectional solidified layer) of the hydrogel precursor liquid again, and then by repeating this process, a hydrogel manufacturing product is obtained in which a plurality of solidified products (cross-sectional solidified layers) are stacked and integrated.

[0134] The apparatus for selectively exposing the hydrogel precursor liquid is not particularly limited, and various types of apparatuses may be used. The apparatuses include (a) an irradiator for irradiating the hydrogel precursor liquid with a laser beam or light focused by a lens or a reflector, (b) an irradiator for irradiating the hydrogel precursor liquid with non-focused light through a mask having a light-transmitting portion with a predetermined pattern, (c) an irradiator for irradiating the hydrogel precursor liquid with light through optical fibers corresponding to a predetermined pattern using a light-guiding member formed by bundling a large number of optical fibers, and (d) an apparatus for repeatedly performing a one-time exposure of the hydrogel precursor liquid for each predetermined range of regions.

[0135] In the device using the mask of (b) above, a mask image consisting of light-transmitting regions and light-impermeable regions may be electro-optically formed in a predetermined pattern as a mask based on the same principle as a liquid crystal display device.

[0136] When the target hydrogel manufacturing product has a fine structure or requires high dimensional accuracy, it is preferable to use an irradiator that scans a laser beam with a small spot diameter as a means for selectively irradiating the hydrogel precursor liquid with light.

[0137] When the hydrogel precursor liquid is contained in a container, the light irradiation surface (e.g., the scanning surface of the converging light) may be the liquid surface of the hydrogel precursor liquid or the contact surface with the wall of the light-transmitting container. When the liquid surface of the hydrogel precursor liquid or the contact surface with the container wall is used as the light irradiation surface, the light may be irradiated directly from the outside of the container or through the container wall.

[0138] As described above, the hydrogel manufactured product of the present invention can be prepared by an optical stereoscopic modeling method such as an optical lamination modeling method. In the optical stereoscopic modeling method, after a specific part of the hydrogel precursor liquid is cured, the light irradiation position (irradiation surface) is moved continuously or stepwise from the cured part to the uncured part, so that the cured part is laminated to obtain the desired three-dimensional shape. Here, the irradiation position movement can be performed by various methods, for example, any one of moving the light source, the storage container of the hydrogel precursor liquid, and the cured part of the hydrogel precursor liquid, or additionally supplying the hydrogel precursor liquid to the storage container.

[0139] A commercially available stereolithography machine can be used. An example of a commercially available stereolithography machine is FORM2 (manufactured by Formlabs).

[0140] Preparation method of the third form

[0141] The preparation method of the hydrogel manufacturing product of the third form can be cited as a casting method using a casting mold. In this method, a casting mold as a template is made. As a method for making a casting mold, a material jetting method, a stereolithography method, a binder jetting method, a fused deposition molding (FDM) method, and a mold made using a 3D printer can be used. The mold can also be obtained by computer numerical control (CNC) cutting.

[0142] The hydrogel precursor liquid is injected / filled into the hollow portion of the mold thus prepared. When the mold is made of a translucent resin, if the photoinitiator for the hydrogel precursor liquid is set to a UV curable type, the hydrogel precursor liquid can be easily cured with a UV lamp.

[0143] When a mold is formed using a non-transmissive resin, if the hydrogel precursor liquid is made heat-curable using a thermal initiator, the hydrogel precursor liquid can be cured by thermal energy.

[0144] After the hydrogel precursor liquid is solidified by these methods, the mold can be removed by peeling or crushing to take out the hydrogel product.

[0145] After generally describing preferred embodiments of the present invention, further understanding can be obtained by reference to certain specific examples, which are provided here merely for illustrative purposes, rather than for limiting. In the description of the following examples, unless otherwise indicated, numerals represent the numerals by weight ratio.

[0146] Example

[0147] Hereinafter, examples of the present invention will be described, but the present invention is not limited to these examples.

[0148] Example 1

[0149] Preparation of hydrogel precursor solution

[0150] 59.9 parts by mass of potassium acrylate (manufactured by Nippon Shokubai Co., Ltd.), 40.0 parts by mass of pure water, and 0.1 parts by mass of ammonium persulfate (manufactured by Wako Pure Chemical Industries, Ltd.) as an initiator were stirred and filtered to remove impurities, etc. Finally, vacuum degassing was performed for 10 minutes to obtain a uniform liquid hydrogel precursor solution.

[0151] Making fracture limit test model: mold modeling

[0152] A polytetrafluoroethylene (PTFE) block was cut to form a test pattern with a depth of 5 mm (made into a dumbbell No. 3 shape according to JIS K 6251). The test pattern was filled with a hydrogel precursor liquid and left in a nitrogen atmosphere for 24 hours to cure. The fracture limit test piece was used as a fracture limit test piece, and the fracture limit was measured by the method shown below.

[0153] Making compression stress test model: mold shaping

[0154] A test pattern (30 mm × 30 mm × 10 mm) was formed by cutting a polytetrafluoroethylene (PTFE) block. The test pattern was filled with a hydrogel precursor solution and placed in a nitrogen atmosphere for 24 hours to solidify, thereby obtaining a 30 mm × 30 mm × 10 mm hydrogel manufacturing product. The compression stress test was performed by the method shown below.

[0155] Modeling of surgical procedures for incision and suturing trials: mold modeling

[0156] A stereolithography modeling device (FORM2, manufactured by Formlabs) was used to make a mold simulating the substantial part of the kidney. The hydrogel precursor solution was flowed into the mold and placed in a nitrogen atmosphere for 24 hours to solidify. The mold was removed to make a model simulating surgical operation of the kidney. The model was cut with an electrosurgical knife and sutured with surgical sutures.

[0157] Example 2

[0158] Preparation of hydrogel precursor solution

[0159] 49.9 parts by mass of potassium acrylate (manufactured by Nippon Shokubai Co., Ltd.), 40.0 parts by mass of pure water, 10.0 parts by mass of dimethylacrylamide (manufactured by KJ Chemical Co., Ltd.) as a polymerizable monomer, and 0.1 parts by mass of ammonium persulfate (manufactured by Wako Pure Chemical Industries, Ltd.) as an initiator were stirred and filtered to remove impurities, etc. Finally, vacuum degassing was performed for 10 minutes to obtain a uniform liquid hydrogel precursor solution.

[0160] Then, a fracture limit test model, a compression stress test model, and a surgical model were prepared using the same method as in Example 1, and subjected to a fracture limit test, a compression stress test, an incision test using an electrosurgical knife, and a suturing test using surgical sutures.

[0161] Example 3

[0162] Preparation of hydrogel precursor solution

[0163] While stirring 40.0 parts by mass of pure water, a layered clay mineral containing components of [Mg 5.34 Li 0.66 Si8O 20 (OH)4]Na -0.667.0 parts by mass of synthetic hectorite (LAPONITE RD, manufactured by Rockwood Additives) was added and stirred, and further 0.3 parts by mass of etidronic acid (manufactured by Tokyo Chemical Industry Co., Ltd.) was added as a dispersant and stirred to prepare a dispersion.

[0164] To the obtained dispersion, 52.6 parts by mass of potassium acrylate (produced by Nippon Shokubai Co., Ltd.) was added.

[0165] 0.1 parts by mass of ammonium persulfate (manufactured by Wako Pure Chemical Industries, Ltd.) was added as an initiator and stirred, and impurities were removed by filtration. Finally, vacuum degassing was performed for 10 minutes to obtain a hydrogel precursor solution that was a uniform liquid.

[0166] Then, a fracture limit test model, a compression stress test model, and a surgical model were prepared using the same method as in Example 1, and subjected to a fracture limit test, a compression stress test, an incision test using an electrosurgical knife, and a suturing test using surgical sutures.

[0167] Example 4

[0168] Preparation of hydrogel precursor solution

[0169] After stirring 58.0 parts by mass of potassium acrylate (manufactured by Nippon Shokubai Co., Ltd.) and 40.0 parts by mass of pure water, 1.9 parts by mass of triethoxyvinylsilane (manufactured by Wako Pure Chemical Industries, Ltd.) as a vinyl silane was added and stirred for 30 minutes. Then, 0.1 parts by mass of ammonium persulfate (manufactured by Wako Pure Chemical Industries, Ltd.) was added as an initiator and stirred, and impurities were removed by filtration. Finally, vacuum degassing was performed for 10 minutes to obtain a uniform liquid hydrogel precursor solution.

[0170] Then, a fracture limit test model, a compression stress test model, and a model for performing surgical operations were prepared using the same method as in Example 1, and subjected to a fracture limit test, a compression stress test, an incision test using an electrosurgical knife, and a suturing test using surgical sutures according to the following methods.

[0171] Example 5

[0172] Preparation of hydrogel precursor solution

[0173] A hydrogel precursor liquid was obtained in the same manner as in Example 4 except that 0.1 parts by mass of 1-hydroxycyclohexyl phenyl ketone [trade name: Irgacure 184] (manufactured by BASF SE) was used as the initiator instead of ammonium persulfate.

[0174] Inkjet Manufacturing (Material Jetting)

[0175] Using a 3D printer (MateriART-3DU1, manufactured by MICROJET) that utilizes inkjet of the above-mentioned material and a hydrogel liquid precursor as a modeling agent, a fracture limit test model, a compression stress test model, and a model for performing surgical operations were directly molded in the same shape as in Example 1, and subjected to fracture limit tests, compression stress tests, incision tests using an electrosurgical knife, and suturing tests using surgical sutures according to the following methods.

[0176] Example 6

[0177] Preparation of hydrogel precursor solution

[0178] A hydrogel precursor liquid was obtained in the same manner as in Example 4 except that 0.1 parts by mass of 1-hydroxycyclohexyl phenyl ketone [trade name: Irgacure 184] (manufactured by BASF SE) was used as the initiator instead of ammonium persulfate.

[0179] Stereolithographic manufacturing

[0180] Using a 3D printer utilizing stereolithography (Form2, manufactured by Formlab), the above-mentioned hydrogel precursor liquid was used as the modeling ink to directly model a fracture limit test model, a compression stress test model, and a model for performing surgical operations in the same shape as in Example 1, and subjected to a fracture limit test, a compression stress test, an incision test using an electrosurgical knife, and a suturing test using surgical sutures according to the following method.

[0181] Comparative Example 1

[0182] Preparation of hydrogel precursor solution

[0183] 59.9 parts by mass of dimethylacrylamide (manufactured by KJ Chemical Co., Ltd.), 40.0 parts by mass of pure water, and 0.1 parts by mass of ammonium persulfate (manufactured by Wako Pure Chemical Industries, Ltd.) as an initiator were stirred, and impurities were removed by filtration. Finally, vacuum degassing was performed for 10 minutes to obtain a uniform liquid hydrogel precursor solution.

[0184] Then, a fracture limit test model, a compression stress test model, and a model for performing surgical operations were prepared using the same method as in Example 1, and subjected to a fracture limit test, a compression stress test, an incision test using an electrosurgical knife, and a suturing test using surgical sutures according to the following methods.

[0185] Comparative Example 2

[0186] Using a 3D printer utilizing a material jetting method (AGLISTA, manufactured by KEYENCE) and a modeling agent (AR-M2, manufactured by KEYENCE), a fracture limit test model, a compression stress test model, and a surgical model were directly molded in the same shape as in Example 1, and subjected to a fracture limit test, a compression stress test, an incision test using an electrosurgical knife, and a suturing test using surgical sutures according to the following method.

[0187] Comparative Example 3

[0188] Using a 3D printer utilizing stereolithography (Form2, manufactured by Formlab) and a transparent resin (manufactured by Formlabs), a fracture limit test model, a compression stress test model, and a model for performing surgical operations were directly molded in the same shape as in Example 1, and subjected to fracture limit tests, compression stress tests, incision tests using an electrosurgical knife, and suturing tests using surgical sutures according to the following methods.

[0189] Evaluation of fracture limit

[0190] The fracture limit test model of each embodiment and comparative example was tested at a tensile speed of 500 mm / min using a tensile strength tester (AG-10kNX, manufactured by Shimadzu Corporation) according to JIS K 6251. In the tensile test, the elongation was calculated from the change in the distance between the marking lines to evaluate the fracture limit. No sample deformation was found in this tester, and the measurement limit exceeded 10 kN. The model with an error was considered to be out of the measurement range.

[0191] Evaluation of compressive stress

[0192] The compression testing machine and measurement method used to evaluate the compressive stress are as follows.

[0193] A universal testing machine (manufactured by Shimadzu Corporation, AG-I) was used, and a load cell of 1 kN and a compression fixture for 1 kN were set, and the compression stress test models of the above-mentioned embodiments and comparative examples were installed. The compression stress applied to the load cell was recorded on a computer, and the stress corresponding to the displacement was plotted to evaluate the compression stress at 60% compression. No sample deformation was found in this testing machine, and the measurement limit exceeded 1 kN, and the manufacturing model with an error was regarded as exceeding the measurement range.

[0194] Evaluation of the applicability and sutureability of energy devices

[0195] The model for performing surgical operations of each of the examples and comparative examples was subjected to an incision test using an electrosurgical knife as an energy device, and a suturing test using surgical sutures.

[0196] The incision test used an electrosurgical knife PROG (DS3M, manufactured by Morita Co., Ltd.), installed with a C-1 blade, set to CUT mode, and pressed the blade against the object to cut a 30 mm long, 10 mm deep incision. Grade A was when the model was burned while the incision was formed, and Grade B was when the model did not react or the blade could not cut.

[0197] In the suturing test, after making an incision of 30 mm in length and 10 mm in depth with a cutter, LTR-1 training needle suture (manufactured by Fujimori Sangyo Co., Ltd.) was used as the surgical needle and thread. After threading the needle three times in a Z shape across the incision, the two ends were pinched to confirm whether the model could be lifted. The possible case was judged as being able to cope with the suturing operation and was judged as Grade A. The case where the model broke when the needle was inserted, the model was damaged and the thread fell off when it was lifted, or the model was too hard for the needle to enter was judged as Grade B.

[0198] The evaluation results are shown in Table 1.

[0199] Table 1-1

[0200]

[0201] Table 1-2

[0202]

[0203] As can be seen from the results in Table 1, Examples 1 to 6 are applicable to electric scalpels compared to Comparative Examples 1 to 3. Examples 3 to 6 can also cope with suturing.

[0204] Compared with Comparative Example 1, Examples 2 to 6 have physical properties of higher fracture limit and higher compressive stress.

[0205] Comparative Examples 2 and 3 are very hard and are not suitable for use as models for medical personnel to practice skills.

[0206] Having now fully described embodiments of the present invention, it will be apparent to those skilled in the art that many changes and modifications may be made thereto without departing from the spirit and scope of the embodiments of the present invention set forth herein.

[0207] This patent application is based upon and claims the benefit of priority from Japanese Patent Application No. 2019-216938 filed in the Japan Patent Office on November 29, 2019, the disclosure of which is hereby incorporated herein by reference in its entirety.

Claims

1. Use of a hydrogel precursor liquid in the manufacture of a model for medical personnel to perform surgical operations, the hydrogel precursor liquid comprising: Metal salts of (meth)acrylic acid; Vinyl silane; as well as water.

2. The use according to claim 1, wherein the hydrogel precursor liquid further comprises a polymerizable monomer.

3. The use according to claim 1 or 2, wherein the hydrogel precursor liquid further comprises a mineral dispersible in water.

4. A method for manufacturing a hydrogel manufactured product, wherein the hydrogel manufactured product is a model for performing a surgical operation for medical personnel, the method comprising: forming a liquid film of the hydrogel precursor liquid according to any one of claims 1 to 3; solidifying the liquid film to form a layer; as well as The forming and curing steps are repeated to stack the layers.

5. The manufacturing method according to claim 4, wherein: The liquid film is formed by inkjet printing.

6. A method for manufacturing a hydrogel manufactured product, wherein the hydrogel manufactured product is a model for performing a surgical operation for medical personnel, the method comprising: exposing the hydrogel precursor liquid according to any one of claims 1 to 3 to cure the hydrogel precursor liquid to form a layer; as well as The exposure is repeated to sequentially form and stack the layers.

7. A method for manufacturing a hydrogel manufactured product, wherein the hydrogel manufactured product is a model for performing surgical operations for medical personnel, the method comprising: Injecting the hydrogel precursor liquid according to any one of claims 1 to 3 into a mold; solidifying the hydrogel precursor liquid; as well as The mold is removed.

8. A hydrogel manufactured product, which is a model for medical personnel to perform surgical operations, and which comprises a hydrogel formed by curing the hydrogel precursor liquid according to any one of claims 1 to 3.

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