WO2019230968A1

WO2019230968A1 - Hydrogel structure and method for producing same

Info

Publication number: WO2019230968A1
Application number: PCT/JP2019/021838
Authority: WO
Inventors: 広治網代; 諒川谷; 祐賀子中井; 將行福嶋; 味村　裕; 禎宏加藤
Original assignee: 古河電気工業株式会社; 国立大学法人奈良先端科学技術大学院大学
Priority date: 2018-06-01
Filing date: 2019-05-31
Publication date: 2019-12-05
Also published as: JPWO2019230968A1; JP7311864B2

Abstract

A hydrogel structure 10 according to the present invention is characterized by containing a first polymer 1 and a second polymer 2 which is entangled with the first polymer, wherein the first polymer 1 is a first mesh structure which is formed by polymerizing and cross-linking a first monomer, the second polymer 2 is a second mesh structure which is formed by polymerizing and cross-linking a second monomer, the first monomer has a Q-value within a range of 0.001 to 0.199 and an e-value within a range of -8.60 to 0, and the second monomer has a Q-value within a range of 0.200 to 16.000 and an e-value within a range of 0.01 to 3.70. The hydrogel structure 10 according to the present invention has excellent mechanical properties.

Description

Hydrogel structure and manufacturing method thereof

The present invention relates to a hydrogel structure and a manufacturing method thereof.

Hydrogel has a three-dimensional network structure formed by polymerization and crosslinking of a plurality of monomers, and contains a solvent such as water inside the three-dimensional network structure. And according to the kind of monomer or solvent, hydrogel shows various characteristics.

Generally, hydrogel has excellent compressive strength but low tensile strength. Therefore, hydrogels are required to improve mechanical strength such as tensile strength.

For example, Patent Document 1 discloses that a step of forming a first network structure by polymerizing and crosslinking a first monomer component, a second monomer component after introducing the second monomer component into the first network structure, Forming a polymer in the first network structure by polymerizing the monomer component, and further forming a second network structure in the first network structure by further crosslinking. A method for producing a structural hydrogel is described. In the hydrogel described in Patent Document 1, the first monomer component and the second monomer component each form a network structure, and these network structures penetrate each other.

Patent Document 2 describes a method for producing a gel having a semi-interpenetrating network structure in which a non-crosslinked polymer invades and physically entangles into a network structure composed of a crosslinked polymer. In the gel described in Patent Document 2, one polymer forms a network structure, and the other polymer enters the network structure.

As described above, the hydrogel structures disclosed in Patent Documents 1 and 2 have a structure in which another network structure or polymer has entered the network structure (hereinafter also referred to as “interpenetrating network structure”). , The mechanical strength of the gel is increased.

However, when producing a hydrogel structure having such an interpenetrating network structure, the reactivity of the monomer, polymerization initiator, crosslinking agent, etc. used has not been fully considered. Therefore, after synthesizing one network structure and then injecting the other network structure, or synthesizing the network structure and then injecting the polymer into the network structure, the next work is completed. It was necessary to do the work.

Specifically, after synthesizing the first network structure, in order to remove unreacted monomers, the solvent is changed many times, or the network structure is immersed in the solvent used in the next step. Had gone. Furthermore, since gelation proceeds even during this operation, it was difficult to produce the final product of the hydrogel structure in the shape and size as designed.

From such a viewpoint, there is a demand for a simple method capable of producing a hydrogel structure without performing the above-described complicated work. However, when synthesis is performed at once using an arbitrarily selected monomer, a hydrogel structure having low mechanical strength may be formed. Since such a hydrogel structure is mechanically fragile, it is desired that a hydrogel structure having high mechanical strength can be produced even when a simple production method is used.

Japanese Patent No. 438297 Japanese Patent No. 5059407

An object of the present invention is to provide a hydrogel structure excellent in mechanical properties and a method for producing a hydrogel structure capable of easily producing such a hydrogel structure.

The gist configuration of the present invention is as follows.
[1] A hydrogel structure containing a first polymer and a second polymer intertwined with the first polymer, wherein the first polymer is a first network structure obtained by polymerizing and crosslinking a first monomer. The second polymer is a second network structure obtained by polymerizing and crosslinking the second monomer, and the first monomer has a Q value in the range of 0.001 to 0.199, and an e value. Is in the range of −8.60 to 0, and the second monomer has a Q value in the range of 0.200 to 16.000 and an e value in the range of 0.01 to 3.70. The hydrogel structure characterized by being.
[2] The first monomer has a Q value in the range of 0.020 or more and 0.170 or less, and an e value in the range of −1.70 or more and −0.80 or less. The hydrogel structure according to the above [1], wherein the Q value is in the range of 0.320 to 1.000 and the e value is in the range of 0.50 to 0.90.
[3] A hydrogel structure containing a first polymer and a second polymer intertwined with the first polymer, wherein the first polymer is a first network structure obtained by polymerizing and crosslinking a first monomer. The second polymer is a second network structure obtained by polymerizing and crosslinking the second monomer, and the first monomer is N-vinylformamide, N-vinylacetamide, N-vinylpyrrolidone, N-vinyl. Caprolactam, N-methyl-N-vinylacetamide, N-allyl stearamide, N, N-methylvinyltoluenesulfonic acid amide, vinyl propionate, 1-vinylimidazole, vinyl butyrate, vinyl acetate, vinyl cinnamate, benzoic acid Group of vinyl acid, vinyl isocyanate, vinyl ethyl ether, and vinyl octadecyl ether One or more of the hydrogel structure is a compound are al selected.
[4] The second monomer is ethyl acrylate, butyl acrylate, methyl acrylate, 2-ethylhexyl acrylate, methyl α-chloroacrylate, acrylamide, ethyl α-acetoxyacrylate, methyl α-cyanoacrylate, 2- The hydrogel structure according to the above [3], which is one or more compounds selected from the group consisting of chloroethyl acrylate, methacrylonitrile, methacrylic acid, hexafluorobutadiene, dimethyl itaconate and α-bromoacrylic acid body.
[5] The above-described structure in which a bridging portion for chemically or physically bonding the first network structure and the second network structure exists between the first network structure and the second network structure. [1] The hydrogel structure according to any one of [4].
[6] At least one functional group of the first functional group obtained by removing one hydrogen atom from the first monomer and the second functional group obtained by removing one hydrogen atom from the second monomer. The hydrogel structure according to the above [5], which is formed by a cross-linking agent having a plurality of
[7] The cross-linked part is formed of a cross-linking agent having a plurality of functional groups of at least one of the third functional group and the fourth functional group, and the third functional group is represented by the following formula (1-1) or formula ( 1-2. The hydrogel structure according to [5] above, wherein the fourth functional group is a structure represented by the following formula (2).

(In Formula (1-1), R1 represents an alkyl group having 1 to 5 carbon atoms or hydrogen, R2 represents a methylene group, and * represents a bond. In Formula (1-2), R5 Represents a methylene group, * represents a bond, R3 represents a methylene group, R4 represents an alkyl group having 1 to 2 carbon atoms or hydrogen, and * represents a bond. Is shown.)
[8] The method for producing a hydrogel structure according to any one of [1] to [7] above, wherein the first monomer, the second monomer, the first monomer, and the second monomer A method for producing a hydrogel structure, comprising: a preparation step of preparing a solution containing a polymerization initiator that polymerizes and crosslinks the solution, and a heating step of heating and gelling the solution.
[9] The solution prepared in the preparation step includes a first functional group obtained by removing one hydrogen atom from the first monomer, and a second functional group obtained by removing one hydrogen atom from the second monomer. The method for producing a hydrogel structure according to the above [8], further comprising a crosslinking agent having a plurality of at least one functional group.
[10] The solution prepared in the preparation step further includes a crosslinking agent having a plurality of functional groups of at least one of a third functional group and a fourth functional group, wherein the third functional group is represented by the following formula (1-1): Alternatively, the method for producing a hydrogel structure according to the above [8], wherein the structure is represented by the formula (1-2), and the fourth functional group is a structure represented by the following formula (2).

(In Formula (1-1), R1 represents an alkyl group having 1 to 5 carbon atoms or hydrogen, R2 represents a methylene group, and * represents a bond. In Formula (1-2), R5 Represents a methylene group, * represents a bond, R3 represents a methylene group, R4 represents an alkyl group having 1 to 2 carbon atoms or hydrogen, and * represents a bond. Is shown.)
[11] The method for producing a hydrogel structure according to any one of [8] to [10], wherein the preparation step and the heating step are performed in one pot.

According to the present invention, it is possible to provide a hydrogel structure excellent in mechanical properties and a method for producing a hydrogel structure capable of easily producing such a hydrogel structure.

It is the schematic which shows the hydrogel structure of one Embodiment according to this invention. It is a figure which shows the state which is carrying out the nitrogen bubbling of the reaction solution used for manufacturing a hydrogel structure. It is a perspective view which shows the outline of the container which put the reaction solution after nitrogen bubbling. It is a top view which shows the outline of the test piece for a tensile test produced by punching out from the hydrogel structure using the punching die.

Hereinafter, the present invention will be described in detail based on embodiments.

As a result of extensive research, the present inventors have considered the reactivity of raw materials such as monomers and polymerization initiators used in the hydrogel structure, and selected raw materials that satisfy a predetermined relationship with respect to the physical properties of each raw material. When used, it has been found that a hydrogel structure having excellent mechanical properties, particularly high breaking strength and high breaking can be obtained even with a simple production method, and the present invention has been completed based on such knowledge.

The hydrogel structure of this embodiment includes a first polymer and a second polymer intertwined with the first polymer, and the first polymer is a first network structure formed by polymerizing and crosslinking a first monomer. The second polymer is a second network structure obtained by polymerizing and crosslinking the second monomer, and the first monomer has a Q value in the range of 0.001 to 0.199, and an e value. Is in the range of −8.60 to 0, and the second monomer has a Q value in the range of 0.200 to 16.000 and an e value in the range of 0.01 to 3.70. It is.

FIG. 1 is a schematic view showing an example of the hydrogel structure of the present embodiment. In FIG. 1, in order to make it easy to visually distinguish the first polymer 1, the second polymer 2, and the cross-linking portion 3 constituting the hydrogel structure, the first polymer 1 is shown for convenience of explanation. The white line, the second polymer 2 is indicated by a black line, and the bridge portion 3 is indicated by a hatched line.

As shown in FIG. 1, the hydrogel structure 10 includes a first polymer 1 and a second polymer 2. The first polymer 1 and the second polymer 2 are entangled with each other and partially bonded at a plurality of portions. The first polymer 1 is a first network structure obtained by polymerizing and crosslinking a first monomer, and the second polymer 2 is a second network structure obtained by polymerizing and crosslinking a second monomer.

The first monomer has a Q value in the range of 0.001 to 0.199 and an e value in the range of −8.60 to 0. The second monomer has a Q value in the range of 0.200 to 16.000 and an e value in the range of 0.01 to 3.70. When the Q value and e value of the first monomer and the second monomer are within the above ranges, the first polymer 1 and the second polymer 2 are partially bonded to each other, and therefore the breaking strength in the hydrogel structure 10 And mechanical properties such as breaking strain can be improved. On the other hand, if the Q value and e value of the first monomer 1 and the second monomer 2 are out of the above ranges, the first polymer 1 and the second polymer 2 do not bind to each other. The mechanical properties cannot be improved sufficiently.

The first monomer preferably has a Q value of 0.020 to 0.180 and an e value of −1.80 to −0.70, more preferably a Q value of 0.020 to 0.170 and The e value is in the range of −1.70 or more and −0.80 or less. The second monomer preferably has a Q value of 0.230 to 3.070 and an e value of 0.30 to 1.28, more preferably a Q value of 0.320 to 1.000 and an e value. Is in the range of 0.50 or more and 0.90 or less. When the Q value and e value of the first monomer and the second monomer are within the above ranges, the above effects are further improved.

Here, the Q value of the monomer is an index representing the degree of conjugation between the double bond of the radical polymerizable monomer and its substituent. The e value of the monomer is an indicator of the electron density of the double bond of the radical polymerizable monomer. Based on styrene (Q value = 1.0, e value = −0.8), the Q value and e value for various monomers have been experimentally determined.

Q and e values of typical monomers are Brandrup, E .; H. Immergut, E .; A. It is described in Grulke's “Polymer Handbook Fourth Edition” (John Wiley & Sons Inc., 1998), and these values may be referred to or calculated by the following method. .

As a method for calculating the Q1 value and the e1 value of the monomer M1, first, a monomer M1 whose Q1 value and e1 value are unknown and a monomer M2 whose Q2 value and e2 value are known are mixed in various molar ratios F (= [M1] / [M2]). At this time, the ratio f (= d [M1] / d [M2]) of the consumption amount of each monomer in the initial stage of polymerization is calculated from a measurement method such as gas chromatography. Here, since F and f satisfy the relationship of the following formula (A), F {(f−1) / f} is plotted against {F (2 / f)} and linearly approximated. For the resulting graph, the slope is r1 and the vertical axis intercept is -r2.

F {(f-1) / f} = r1 {F (2 / f)}-r2 equation (A)

And T. Alfredy and C.I. C. By substituting the Q2 value and the e2 value of r1, r2, and the monomer M2 obtained by the above method into the following formulas (B) and (C) proposed by Price, the Q1 value of the monomer M1 and The e1 value can be calculated.

r1 = (Q1 / Q2) exp [-e1 (e1-e2)] Formula (B)
r2 = (Q2 / Q1) exp [-e2 (e2-e1)] Formula (C)

Examples of the first monomer satisfying the above Q value and e value include N-vinylformamide (NVF) (Q = 0.08 to 0.14, e = −1.7 to −1.6), N— Vinylacetamide (NVA) (Q = 0.16, e = −1.57), N-vinylpyrrolidone, N-vinylcaprolactam (NVCAP) (Q = 0.14, e = −1.18), N-methyl -N-vinylacetamide (MNVA), N-allyl stearamide, N, N-methylvinyltoluenesulfonic acid amide, vinyl propionate, 1-vinylimidazole, vinyl butyrate, vinyl acetate (VACe) (Q = 0.026) E = −0.88), vinyl cinnamate (VCinn) (Q = 0.18, e = −0.76), vinyl benzoate, vinyl isocyanate, vinyl ethyl ether, and vinyl octade One or more compounds selected from the group of sil ethers. In view of the above Q and e values, the first monomer is preferably one or two selected from the group of NVF, NVA, VACe, N-vinyl pyrrolidone, NVCAP, MNVA, vinyl benzoate, and vinyl isocyanate. One or more compounds, more preferably one or more compounds selected from the group of NVF, NVA, VACe, NVCAP, and MNVA. As the first monomer, one type of monomer may be used alone, or two or more types of monomers may be used in combination. The Q value and e value of NVF are values estimated based on the relative values of the Q value and e value of vinyl caprolactam (7 carbons) and vinyl pyrrolidone (5 carbons).

Examples of the second monomer that satisfies the above Q value and e value include acrylate monomers, such as ethyl acrylate (EAc) (Q = 0.41, e = 0.55), butyl acrylate (BAc) ( Q = 0.38, e = 0.85), methyl acrylate (MAc) (Q = 0.45, e = 0.64), 2-ethylhexyl acrylate, methyl α-chloroacrylate, acrylamide, α-acetoxy Ethyl acrylate (Q = 0.52, e = 0.77), methyl α-cyanoacrylate, 2-chloroethyl acrylate, methacrylonitrile (Q = 0.86, e = 0.68), methacrylic acid ( Q = 0.98, e = 0.62), hexafluorobutadiene (Q = 0.82, e = 0.58), dimethyl itaconate (Q = 0.73, e = 0.57) and α-bromo Acrylic acid Is one or more compounds selected from the group. In view of the above Q and e values, the second monomer is preferably selected from the group of EAc, BAc, MAc, methyl α-chloroacrylate, acrylamide, ethyl α-acetoxyacrylate, and 2-chloroethyl acrylate. One or more compounds selected from the group consisting of EAc, BAc, MAc, and ethyl α-acetoxyacrylate are more preferable. As the second monomer, one type of monomer may be used alone, or two or more types of monomers may be used in combination.

Here, as the polymerization degree of the first network structure and the polymerization degree of the second network structure increase, the mechanical properties of the hydrogel structure 10 are improved. Further, as the degree of cross-linking of the first network structure and the degree of cross-linking of the second network structure increase, the network density of the first network structure and the network density of the second network structure increase, so that the hydrogel structure While the mechanical strength of 10 increases, the degree of swelling of the hydrogel structure 10 decreases. Therefore, the degree of polymerization and the degree of crosslinking of the first network structure and the second network structure are appropriately selected according to the characteristics required for the hydrogel structure 10.

Further, a bridging portion 3 for chemically or physically bonding the first network structure and the second network structure may exist between the first network structure and the second network structure. When manufacturing the hydrogel structure 10 using the crosslinking agent mentioned later, the some bridge | crosslinking part 3 is formed in the hydrogel structure 10, and several bridge | crosslinking parts 3 are the 1st network structure and the 2nd network structure. It intervenes between. In this case, the first network structure and the second network structure are bonded to each other via the plurality of bridging portions 3 in addition to the plurality of bonding portions. Here, the chemical bond is a covalent bond such as a carbon-carbon bond, an ether bond, an ester bond or an amide bond, or an interaction due to an intermolecular force such as an ionic bond or a hydrogen bond. Are molecular structures of similar composition, aggregates of compounds, and entanglement of molecular chains.

As the cross-linked portion 3 increases, the number of joints between the first network structure and the second network structure increases, so that the mechanical properties of the hydrogel structure 10 are improved, while the degree of swelling of the hydrogel structure 10 is increased. Will decline. Therefore, the number of cross-linking parts 3 included in the hydrogel structure 10 is appropriately selected according to the characteristics required for the hydrogel structure 10. For example, the number of cross-linking portions 3 in the hydrogel structure 10 can be indirectly calculated by the molar mass of the cross-linking portions 3 included in the hydrogel structure 10.

The cross-linking part 3 includes a plurality of cross-linking agents having at least one functional group of a first functional group obtained by removing one hydrogen atom from the first monomer and a second functional group obtained by removing one hydrogen atom from the second monomer. Or a cross-linking agent having a plurality of functional groups of at least one of a third functional group and a fourth functional group described later. The first functional group, the second functional group, the third functional group, and the fourth functional group each have a cis type and a trans type. In particular, the cross-linking part 3 is preferably formed by a cross-linking agent having the same reaction rate as that of the first monomer or the second monomer. Therefore, the cross-linking agent has a structure of each of the first monomer and the second monomer. It is preferable to select a structure similar to the structure in which is bonded.

Examples of the cross-linking agent include a chain monomer having two functional groups of at least one of a first functional group and a second functional group that are polymerizable substituents, or a third functional group and a second functional group that are polymerizable substituents. It is a chain monomer having two functional groups of at least one of four functional groups. Such a chain monomer has one of these polymerizable substituents at both ends. The type of the crosslinking agent is appropriately selected according to the types of the first polymer, the second polymer, and the polymerization initiator.

In the following, the cross-linking agent having one third functional group at each end is an AA cross-linking agent, the cross-linking agent having one fourth functional group at each end is a BB cross-linking agent, and the third functional group is at one end. A cross-linking agent having one and one fourth functional group at the other end is referred to as an AB cross-linking agent. Among these cross-linking agents, the cross-linking agent is preferably an AB cross-linking agent from the viewpoint of easily forming the cross-linking part 3.

As for the third functional group, for example, the structure bonded to the vinyl group is similar to the structure bonded to the first monomer, and more specifically, the following formula (1-1) or formula (1-2) ).

(In Formula (1-1), R1 represents an alkyl group having 1 to 5 carbon atoms or hydrogen, R2 represents a methylene group, and * represents a bond. In Formula (1-2), R5 Represents a methylene group, * represents a bond, R3 represents a methylene group, R4 represents an alkyl group having 1 to 2 carbon atoms or hydrogen, and * represents a bond. Is shown.)

The fourth functional group is, for example, a structure represented by the following formula (2), assuming that the structure bonded to the vinyl group is similar to the structure bonded to the second monomer. is there.

In the formula (2), R3 represents a methylene group, R4 represents an alkyl group having 1 to 2 carbon atoms or hydrogen, and * represents a bond.

* In formula (1-1), formula (1-2), and formula (2) is bonded to both ends of a chain organic compound group, for example. The chain organic compound group may be a straight chain hydrocarbon group or a partially branched chain hydrocarbon group. The organic compound group may have a functional group such as a hydroxy group or an ether bond.

For example, when the first monomer is N-vinylformamide represented by the following formula (3), the specific structural formula of the AA crosslinking agent is represented by the following formula (4-1), and the first monomer is In the case of vinyl acetate, the specific structural formula of the AA crosslinking agent is represented by the following formula (4-2). In any of these structural formulas, the two third functional groups may be cis-type, or one third functional group may be trans-type and the other third functional group may be cis-type. The same applies to formulas (6) and (7) described later.

In addition, when the second monomer is ethyl acrylate represented by the following formula (5), a specific structural formula of the BB crosslinking agent is represented by the following formula (6).

Further, when the first monomer is N-vinylformamide represented by the above formula (3) and the second monomer is ethyl acrylate represented by the above formula (5), a specific structural formula of the AB crosslinking agent Is represented by the following formula (7).

In the hydrogel structure 10 described above, whether or not the first network structure and the second network structure are bonded to each other can be confirmed by OH detection measurement after hydrolysis of the hydrogel structure 10. An example of this measurement method is as follows.

First, the hydrogel structure 10 previously swollen with water is immersed in 1 mol / L hydrochloric acid for 72 hours, and then the hydrogel structure is washed in ion-exchanged water. Thereafter, the ion-exchanged water is replaced three times every 12 hours, and the washing is repeated. Subsequently, 10 mg of the hydrogel structure dried after washing is added to 400 μL of water to prepare a sample solution. Then, an alcohol measurement assay (colorimetric) for determining the primary alcohol (STA-620, manufactured by Cell Biolabs) is added to the sample solution, and the difference in color of the sample solution is confirmed. The fact that the first network structure and the second network structure can be confirmed to be bonded to each other by the change in the color of the sample solution is as follows.

By selectively hydrolyzing the ester bond in the hydrogel structure 10, the second network structure crosslinked by the ester bond derived from the BB crosslinking agent has a chain polymer having a carboxyl group and a low molecular weight Decomposes into primary alcohol of the compound. This low molecular weight compound is removed from the hydrogel structure during washing. On the other hand, the 1st network structure maintains the crosslinked structure with the AA crosslinking agent. Moreover, this crosslinked structure is decomposed into a chain polymer derived from the second network structure and a first network structure having a primary hydroxy group by hydrolysis of the AB crosslinking agent. Since the chain polymer derived from the second network structure is not a low molecular compound, it remains in the hydrogel structure even after washing. And the structure derived from the primary hydroxy group which this 1st network structure has can be confirmed by the said alcohol measurement assay (colorimetric) as pseudo primary alcohol. On the other hand, in the hydrogel structure in which the first network structure and the second network structure are not bonded to each other, the color of the sample solution changes even when the alcohol measurement assay is added to the sample solution in the above measurement method. Or a change in color is small compared to the measurement method of the hydrogel structure 10.

Further, the hydrogel structure 10 includes a solvent such as water or an organic solvent. The solvent in the hydrogel structure 10 is taken into, for example, the network of the first network structure, the network of the second network structure, or between the first network structure and the second network structure. . The amount and type of the solvent contained in the hydrogel structure 10 depends on the use of the hydrogel structure 10, the first monomer, the second monomer, the polymerization initiator, the type of raw material of the hydrogel structure such as a crosslinking agent, It is selected appropriately. In addition, as the solvent, one type of solvent may be used alone, or two or more types of solvents may be used in combination.

The hydrogel structure 10 includes compounds such as a first monomer, a second monomer, a polymerization initiator, and a crosslinking agent within a range that does not lower the effect of improving the mechanical properties such as breaking strength and breaking strain described above. Unreacted material derived from it may be included.

The hydrogel structure 10 of the embodiment can be used in various fields. As an example, it can be used for a water retention material. Moreover, it can be applied to medical materials as a high-strength gel material with high biocompatibility. For example, as a highly functional biomaterial or low friction material, an artificial blood vessel utilizing the light transmittance of the hydrogel structure, an artificial joint cartilage utilizing the low friction surface of the hydrogel structure, an antithrombotic material, an artificial organ It can be suitably used for surfaces such as artificial joints. In addition, it can be used for daily goods such as cushion materials and industrial materials. For example, diapers, hygiene products, sustained release materials, civil engineering materials, building materials, communication materials, soil modifiers, contact lenses, intraocular lenses, hollow fibers, fuel cell materials, battery membranes (separators), impact resistant materials, And can be suitably used for cushions. Moreover, it can be applied to various fields as a friction reducing member such as a film, a sheet, and a tube. For example, it can be suitably used for the outer surface of medical instruments such as endoscopes and catheters. When a hydrogel structure having a shape such as a film shape, a sheet shape, or a tube shape is mounted on the outer surface of a medical device such as an endoscope or a catheter, the medical device when the medical device is inserted into the patient's body Since the frictional resistance with the body is reduced, it is possible to greatly reduce the patient's pain during surgery and examination.

Next, a method for manufacturing the hydrogel structure 10 of the embodiment will be described.

The manufacturing method of the hydrogel structure 10 of the embodiment includes a preparation step S10 and a heating step S20.

In the preparation step S10, a solution containing a first monomer, a second monomer, and a polymerization initiator that polymerizes and crosslinks the first monomer and the second monomer is prepared.

In addition, as a solution prepared in preparation process S10, after purchasing the solution which has the structure similar to the solution containing one monomer and a polymerization initiator among 1st monomer and 2nd monomer, it is contained in the said solution. The other monomer that has not been added may be added to the solution and mixed. Moreover, after purchasing the solution which has the structure similar to the solution which does not contain a 1st monomer and a 2nd monomer but contains a polymerization initiator, it adds and mixes the 1st monomer and the 2nd monomer to the said solution, and mixes May be. Further, the solution may be prepared without purchasing any of the above solutions. Below, preparation process S10 which prepares a solution, without purchasing either of said solutions is demonstrated.

The first monomer used in the method for producing the hydrogel structure 10 has a Q value in the range of 0.001 to 0.199 and an e value in the range of −8.60 to 0. The second monomer has a Q value in the range of 0.200 to 16.000 and an e value in the range of 0.01 to 3.70.

In the manufacturing method of the hydrogel structure of the embodiment, the reactivity of the first monomer and the second monomer as raw materials, in particular, the difference in the reaction rate between the first monomer and the second monomer is utilized. It was found that a hydrogel structure excellent in mechanical properties can be produced easily and in a short time without waiting for completion of each operation as described above when the value is in the above range.

That is, when the Q value and e value of the first monomer and the Q value and e value of the second monomer are within the above ranges, the polymerization reaction, the crosslinking reaction, and the crosslinking agent of the first monomer and the second monomer are further used. In some cases, these reactions and a plurality of operations associated with the formation reaction of the bridging portion 3 can be performed at the same time, so that the shape change of the hydrogel structure during synthesis is reduced, which is simpler and shorter in time than conventional manufacturing methods. In addition, the final product of the hydrogel structure can be easily manufactured in the shape and size as designed.

On the other hand, if the Q value and e value of the first monomer and the Q value and e value of the second monomer are outside the above ranges, the previous work is completed as in the conventional method for producing a hydrogel structure. Then you need to do the following: Therefore, compared with the manufacturing method of the hydrogel structure 10 of the embodiment, the work is complicated and takes a long time. Furthermore, the manufactured hydrogel structure has mechanical properties such as breaking strength and breaking strain that are lowered, and it is not easy to produce the designed shape and size.

Also, the polymerization initiator used in the method for producing a hydrogel structure polymerizes and crosslinks the first monomer and the second monomer, and bonds the first network structure and the second network structure to each other. The polymerization initiator used is appropriately selected according to the types of the first monomer and the second monomer.

For example, when the first monomer is NVF and the second monomer is EAc, examples of the polymerization initiator include azobisisobutyronitrile (AIBN).

Further, the solvent used as a raw material for the solution prepared in the preparation step S10 has compatibility with the first monomer and the second monomer. The solvent used is appropriately selected according to the types of the first monomer and the second monomer. Specific examples include acetonitrile, ethanol, methanol, propanol, acetone, dimethyl sulfoxide (DMSO), water, N, N-dimethylformamide (DMF), and the like. For example, when the first monomer is NVF and the second monomer is EAc, examples of the solvent include dimethyl sulfoxide (DMSO), water, N, N-dimethylformamide (DMF), and the like.

The solution prepared in the preparation step S10 is prepared by adding and mixing the first monomer, the second monomer, and the polymerization initiator in a solvent and dissolving them. The timing of adding the first monomer, the second monomer, and the polymerization initiator to the solvent is not particularly limited, and since the procedure is simple, the first monomer, the second monomer, and the polymerization initiator are added. It is preferable to add all at once.

The content of the first monomer in the solution is in the range of 0.01 mol / L to 10.00 mol / L, preferably 0.05 mol / L to 1.00 mol / L. When the content of the first monomer in the solution is within the above range, sufficient reactivity can be exhibited in a shorter time in the heating step S20 described later. In particular, when the content of the first monomer in the solution is 0.05 mol / L or more, the radical collision probability is increased, the reactivity of the solution is further improved, and the content of the first monomer is 1.00 mol / L. When it is below, the mobility of the first monomer and the first polymer in the solvent is sufficiently ensured.

The content of the second monomer in the solution is in the range of 0.01 mol / L to 10.00 mol / L, preferably 0.05 mol / L to 1.00 mol / L. When the content of the second monomer in the solution is within the above range, sufficient reactivity can be exhibited in a shorter time in the heating step S20. In particular, when the content of the second monomer in the solution is 0.05 mol / L or more, the radical collision probability is increased, the reactivity of the solution is further improved, and the content of the second monomer is 1.00 mol / L. When it is below, the mobility of the second polymer in the solvent is sufficiently ensured.

The number of moles (m) of the polymerization initiator relative to the total number of moles (m1 + m2) of the number of moles of vinyl groups of the first monomer (m1) and the number of moles of vinyl groups of the second monomer (m2) contained in the solution The ratio {m / (m1 + m2)} is in the range of 0.0001 to 0.1000, preferably 0.0050 to 0.0300. When the content of the polymerization initiator in the solution is within the above range with respect to the number of moles of all vinyl groups of the first monomer and the second monomer, the polymerization initiator due to oxygen radicals remaining in the solution Since deactivation can be prevented and a sufficient degree of polymerization can be obtained, a hydrogel structure excellent in mechanical properties can be obtained. In particular, when the above ratio is 0.0050 or more, it is possible to avoid a situation in which the polymerization reaction does not sufficiently proceed due to deactivation of the polymerization initiator, and when the above ratio is 0.0300 or less, the first monomer In addition, the second monomers can grow to a certain length or more.

In the above description, the preparation process for preparing a solution without purchasing a solution containing a predetermined compound in advance has been described. However, when a solution containing a predetermined compound is used in advance, the remaining compound is added to the solution. By adding, a solution prepared in the preparation step can be obtained. For example, when using a solution containing a first monomer and a polymerization initiator in advance, the solution (reaction solution) prepared in the preparation step S10 can be obtained by adding the second monomer to the solution. .

In the heating step S20 performed after the preparation step S10, the solution prepared in the preparation step S10 is heated to be gelled.

In the heating step S20, when the solution obtained in the preparation step S10 is heated, the gelation of the solution occurs, and the hydrogel structure of the above-described embodiment can be obtained.

The heating temperature of the solution in the heating step S20 is in the range of 40 ° C to 120 ° C, preferably 45 ° C to 100 ° C. When the heating temperature of the solution is 40 ° C. or higher, the radical generation rate of the polymerization initiator increases. Moreover, evaporation of a solution can be suppressed as the heating temperature of a solution is 120 degrees C or less.

The heating time of the solution in the heating step S20 is 4 hours to 48 hours, preferably 6 hours to 12 hours. When the heating time of the solution is 4 hours or longer, the solution can be sufficiently gelled. Further, when the heating time of the solution is 48 hours or less, excessive progress of gelation can be avoided.

Moreover, it is preferable that the solution prepared in the preparation step S10 further includes the cross-linking agent in addition to the first monomer, the second monomer, and the polymerization initiator. When the solution contains a cross-linking agent, in the resulting hydrogel structure, the mechanical properties are further improved due to the increase in the cross-linked portion 3 and the degree of cross-linking of the first polymer and the second polymer.

In addition, when a solution contains a crosslinking agent, the timing for adding the crosslinking agent in the preparation step S10 to the solution is not particularly limited, and may be the same timing as the first polymer, for example, heating in the heating step S20 The conditions can be the same as the conditions for heating the solution containing no crosslinking agent.

The content of the crosslinking agent in the solution is 0.0001 mol / L or more and 0.5000 mol / L or less, preferably 0.0005 mol / L or more and 0.1000 mol / L or less. When the content of the crosslinking agent in the solution is within the above range, a network structure having an appropriate size is formed in the hydrogel structure, and the hydrogel structure has excellent mechanical strength. In particular, when the content of the cross-linking agent in the solution is 0.0005 mol / L or more and 0.1000 mol / L or less, the hydrogel structure has excellent mechanical strength and the network size becomes too small, so It can be avoided that the solvent cannot be contained in the gel structure.

The solution may further include other additives in addition to the first monomer, the second monomer, the polymerization initiator, and the crosslinking agent. When a solution contains an additive, content of the additive in a solution will not be specifically limited if it is a range which does not reduce said effect.

Moreover, it is preferable to perform the preparation step S10 and the heating step S20 in one pot. When the preparation step S10 and the heating step S20 are performed in one pot, the hydrogel structure can be manufactured by performing a plurality of steps in one container, and therefore the method for manufacturing the hydrogel structure becomes simpler. On the other hand, if the Q value and e value of the first monomer and the second monomer are outside the above ranges, the next operation is performed after completing the previous operation while changing the container as in the conventional manufacturing method. Since it is necessary, it is difficult to manufacture the hydrogel structure of the above embodiment in one pot.

According to the embodiment described above, when the synthesis is performed using the first monomer and the second monomer in which the Q value and the e value satisfy a predetermined relationship, a plurality of steps are continuously performed without waiting for the end of each step. Therefore, the hydrogel structure can be manufactured in a desired shape and size easily and easily. Moreover, the hydrogel structure obtained by such a manufacturing method is excellent in mechanical characteristics.

Although the embodiments have been described above, the present invention is not limited to the above-described embodiments, and includes all aspects included in the concept and claims of the present invention, and various modifications within the scope of the present invention. can do.

Next, examples and comparative examples will be described, but the present invention is not limited to these examples.

Example 1
First, N-hydroxypropyl N-vinylformamide was produced. First, 3.1 g of sodium hydride was prepared in a reaction vessel and washed with tetrahydrofuran (THF). Subsequently, 130 mL of N, N-dimethylformamide (DMF) was added to the reaction vessel under a nitrogen atmosphere, and 9.2 g of N-vinylformamide was added dropwise to the reaction vessel at 0 ° C. Subsequently, the reaction solution in the reaction vessel was stirred for 4 hours at room temperature, and then 18 g of 3-bromo-1-propanol was dropped into the reaction vessel at 0 ° C. Subsequently, after the reaction solution in the reaction vessel was again stirred at room temperature for 7 hours, water was added to the reaction solution to stop the reaction. The reaction solution was extracted and washed with hexane and ethyl acetate, and then the organic phase was dried over magnesium sulfate. Further purification by silica gel column chromatography gave 11.3 g of N-hydroxypropyl N-vinylformamide as a liquid (yield 68%). The synthesis of N-hydroxypropyl N-vinylformamide is represented by the following reaction formula (1).

Next, a crosslinking agent (AB crosslinking agent) represented by the above formula (7) was produced. First, 1.3 g of N-hydroxypropyl N-vinylformamide, 20 mL of triethylamine, and 90 mL of THF as a solvent were prepared in a reaction vessel. Furthermore, 11.8 g of acryl chloride was added into the reaction vessel with a syringe at 0 ° C. The reaction solution was allowed to stir for 1.5 hours, and an excess amount of water was added to the reaction vessel to stop the reaction. Then, after extracting and washing with ethyl acetate, the organic phase was dried with magnesium sulfate. Next, 12.3 g (yield 77%) of a cross-linking agent represented by the formula (7) was obtained as a white solid by purification by silica gel column chromatography. The synthesis of the crosslinking agent represented by the formula (7) is represented by the following reaction formula (2).

Next, a crosslinking agent (AA crosslinking agent) represented by the above formula (4-1) was produced. First, 1.35 g of sodium hydride was prepared in a reaction vessel and washed with THF. Subsequently, 15 mL of DMF was added to the reaction vessel under a nitrogen atmosphere, and 2.88 g of N-vinylacetamide (NVA) was added dropwise to the reaction vessel at 0 ° C. Subsequently, the reaction solution in the reaction vessel was heated to 50 ° C. and stirred for 6 hours, and 3.37 g of bis (4-chlorobutyl) ether was added dropwise to the reaction vessel at 0 ° C. Subsequently, the reaction solution in the reaction vessel was heated again to 50 ° C. and stirred for 10 hours, and then water was added to the reaction solution to stop the reaction. Thereafter, extraction and washing were performed with hexane and ethyl acetate, and the organic phase was dried with magnesium sulfate. Next, 3.65 g (yield: 73%) of a crosslinking agent represented by the formula (4-1) was obtained by purification by silica gel column chromatography. The synthesis of the crosslinking agent represented by the formula (4-1) is represented by the following reaction formula (3).

Moreover, triethylene glycol dimethacrylate (T0948, manufactured by Tokyo Chemical Industry Co., Ltd.) was prepared for the crosslinking agent (BB crosslinking agent) represented by the above formula (6).

Next, the hydrogel structure of Example 1 was manufactured using the raw material manufactured and prepared above. First, 5 mL of dimethyl sulfoxide (DMSO) as a solvent, and N-vinylformamide (NVF) (Q = 0.08 to 0.14, e = −1.7 to −1.6) as the first monomer, 2 monomers represented by ethyl acrylate (EAc) (Q = 0.41, e = 0.55), polymerization initiator as azobisisobutyronitrile (AIBN), and AA crosslinking agent represented by formula (4-1) The cross-linking agent represented by the formula (6) as the cross-linking agent and the BB cross-linking agent, and the cross-linking agent represented by the formula (7) as the AB cross-linking agent have the contents shown in Table 1 in the reaction solution The mixture was poured into a 20 mL screw tube and stirred. Thereafter, as shown in FIG. 2, a septum 23 pierced with

syringes

21 and 22 is attached to a screw tube 24, and nitrogen (N ₂ ) bubbling is performed on the reaction solution 25 for 1 minute as indicated by an arrow. Expelled oxygen in 24.

Next, as shown in FIG. 3, a container 30 is formed by combining two glass plates 31 and four silicon sheets 32, and an opening 30a having an opening size of 1 mm is formed in the formed container 30. The reaction solution 25 bubbled with nitrogen (N ₂ ) was poured with a syringe, and the remainder of the reaction solution 25 was returned to the screw tube 24. Here, the container 30 shown in FIG. 3 is configured so that two rectangular glass plates 31 are maintained in parallel with each other at an interval of 1 mm so that peripheral portions of the glass plates (however, four sides excluding the opening 30a) are maintained. In this case, the silicon sheet 32 is sandwiched between the two portions. Subsequently, the container 30 containing the reaction solution 25 and the screw tube containing the remaining reaction solution 25 are placed in a thermostat set at 60 ° C. with the opening 30a on the upper side as shown in FIG. 24 was set and each reaction solution was reacted for 8 hours. Thereafter, it is visually confirmed that the reaction solution in the container 30 and the reaction solution in the screw tube 24 are gelled, and the hydrogel structure is sufficiently washed with water. The hydrogel structure of Example 1 Manufactured.

(Example 2)
As the first monomer, VACe (Q = 0.026, e = −0.88) is used instead of N-vinylformamide (NVF), and the AA crosslinking agent is represented by the formula (4-2). A hydrogel structure of Example 2 was produced by the same raw materials and production method as Example 1 except that divinyl adipate (A1188, manufactured by Tokyo Chemical Industry Co., Ltd.) was used.

(Example 3)
VACe (Q = 0.026, e = −0.88) is used as the first monomer instead of N-vinylformamide (NVF), and acrylic acid is used as the second monomer instead of ethyl acrylate (EAc). Methyl (MAc) (Q = 0.45, e = 0.64) was used, and divinyl adipate represented by the formula (4-2) (A1188, manufactured by Tokyo Chemical Industry Co., Ltd.) was used as the AA crosslinking agent. Except for this, the hydrogel structure of Example 3 was manufactured using the same raw materials and manufacturing method as in Example 1.

Example 4
Instead of N-vinylformamide (NVF), N-vinylacetamide (NVA) (Q = 0.16, e = −1.57) is used as the first monomer, and ethyl acrylate (EAc) is used as the second monomer. The hydrogel structure of Example 4 using the same raw materials and production method as in Example 1 except that methyl acrylate (MAc) (Q = 0.45, e = 0.64) was used instead of The body was manufactured.

(Comparative Example 1)
Instead of using NVF as the first monomer and not using the second monomer, instead of using vinyl cinnamate (VCinn) (Q = 0.18, e = 0.76), BB crosslinker A hydrogel structure of Comparative Example 1 was produced by the same raw materials and production method as in Example 1 except that the formula (4-2) was used as a crosslinking agent.

(Comparative Example 2)
As the first monomer, N-vinylacetamide (NVA) is used instead of N-vinylformamide (NVF), the second monomer is not used, and azobisisobutyronitrile (AIBN) is used as a polymerization initiator. 2,2′azobis (2-methylpropionamidine) dihydrochloride (V-50) and N, N-5-oxa is used as a cross-linking agent without using an AA cross-linking agent, a BB cross-linking agent and an AB cross-linking agent. According to the same raw materials and production method as in Example 1, except that nonamethylene bis-bis-N-vinylacetamide (5ON-bisNVA) was used and the temperature of the thermostatic bath was 37 ° C. instead of 60 ° C. The hydrogel structure of Comparative Example 2 was produced.

Table 1 shows the types and contents of each component contained in the reaction solutions used in Examples 1 to 4 and Comparative Examples 1 and 2.

<Evaluation of mechanical properties>
First, in order to evaluate the mechanical properties, each manufactured hydrogel structure was cut out using a punching die, and as shown in FIG. 4, dimension a (distance between positions of chuck portions): 25 mm, dimension b: A test piece for a tensile test of a sheet of 6 mm, dimension c: 1 mm, and thickness 1 mm was prepared. The test piece of the produced hydrogel structure was subjected to a mechanical test using EZ-SX (manufactured by Shimadzu Corporation). When conducting a mechanical test of the test piece, the tensile speed is 2 mm / min when the maximum elongation is 0.5 or less, 5 mm / min when the maximum elongation is 0.5 to 2.0, and 2.0 to 5.0. Was set at 20 mm / min, and those at 5.0 or more were set at 40 mm / min. The breaking strain was calculated by the following formula (11). L is the distance between the gauge points (mm) at the time of breaking in the tensile test, and L0 is the original gauge distance (mm) of the test piece before the tensile test. Table 2 shows the results of breaking strength (MPa) and breaking strain.

(L-L0) / L0 model (11)

<Swelling degree test>
The degree of swelling was calculated from the following formula (12). Ws is the weight of the hydrogel structure after swelling, and Wd is the weight of the hydrogel structure at the time of drying. The results of the degree of swelling are shown in Table 2.

(Ws-Wd) / Wd equation (12)

In addition, each manufactured test material (hydrogel structure) produced three test pieces, and expressed the average value (n = 3) of the three data obtained by carrying out the characteristic test about these test pieces. It was shown in 2. In Table 2, the numerical value in parentheses shown on the right side of each value is a standard deviation value (n = 3).

Next, it was confirmed whether or not the first network structure and the second network structure were bonded to each other with respect to the hydrogel structures manufactured in Examples and Comparative Examples. Here, Example 1 having the highest breaking strain and Comparative Example 2 having the lowest breaking strength were compared.

First, the produced hydrogel structure was swollen with water. Subsequently, the swollen hydrogel structure was immersed in 1 mol / L hydrochloric acid for 72 hours, and then the hydrogel structure was washed in 1 L of ion exchange water. Thereafter, the ion exchange water was changed three times every 12 hours, and the washing was repeated. Subsequently, 10 mg of the hydrogel structure dried after washing was added to 400 μL of water to prepare a sample solution. Then, an alcohol measurement assay (colorimetric) for determining the primary alcohol (STA-620, manufactured by Cell Biolabs) was added to the sample solution, and the difference in color of the sample solution was confirmed.

In the hydrogel structure produced in Example 1, since the color of the sample solution was changed, it was found that the first network structure and the second network structure were bonded to each other.

In the hydrogel structure produced in Comparative Example 2, the color of the sample solution did not change. In Comparative Example 2, since the second monomer was not used, the second network structure was not formed.

Further, from the evaluation results of the mechanical properties shown in Table 2, the hydrogel structures of Examples 1 to 4 all have a larger breaking strain than the hydrogel structures of Comparative Examples 1 and 2, and have a certain breaking strength. It can be seen that the strength is maintained and the mechanical properties are excellent.

DESCRIPTION OF SYMBOLS 1 1st polymer 2 2nd polymer 3 Crosslinking part 10 Hydrogel structure

Claims

A hydrogel structure containing a first polymer and a second polymer intertwined with the first polymer,
The first polymer is a first network structure obtained by polymerizing and crosslinking a first monomer;
The second polymer is a second network structure obtained by polymerizing and crosslinking a second monomer;
The first monomer has a Q value in the range of 0.001 to 0.199 and an e value in the range of −8.60 to 0,
The hydrogel structure, wherein the second monomer has a Q value in the range of 0.200 to 16.000 and an e value in the range of 0.01 to 3.70.
The first monomer has a Q value in the range of 0.020 or more and 0.170 or less, and an e value in the range of −1.70 or more and −0.80 or less,
2. The hydrogel structure according to claim 1, wherein the second monomer has a Q value in a range of 0.320 to 1.000 and an e value in a range of 0.50 to 0.90.
A hydrogel structure containing a first polymer and a second polymer intertwined with the first polymer,
The first polymer is a first network structure obtained by polymerizing and crosslinking a first monomer;
The second polymer is a second network structure obtained by polymerizing and crosslinking a second monomer;
The first monomer is N-vinylformamide, N-vinylacetamide, N-vinylpyrrolidone, N-vinylcaprolactam, N-methyl-N-vinylacetamide, N-allyl stearamide, N, N-methylvinyltoluenesulfone One or more selected from the group of acid amide, vinyl propionate, 1-vinylimidazole, vinyl butyrate, vinyl acetate, vinyl cinnamate, vinyl benzoate, vinyl isocyanate, vinyl ethyl ether, and vinyl octadecyl ether Hydrogel structure which is a compound of
The second monomer is ethyl acrylate, butyl acrylate, methyl acrylate, 2-ethylhexyl acrylate, methyl α-chloroacrylate, acrylamide, ethyl α-acetoxyacrylate, methyl α-cyanoacrylate, 2-chloroethyl acrylate The hydrogel structure according to claim 3, which is one or more compounds selected from the group consisting of methacrylonitrile, methacrylic acid, hexafluorobutadiene, dimethyl itaconate and α-bromoacrylic acid.
A bridging portion for chemically or physically bonding the first network structure and the second network structure exists between the first network structure and the second network structure. 5. The hydrogel structure according to any one of 4 above.
The cross-linking part has a plurality of functional groups of at least one of a first functional group obtained by removing one hydrogen atom from the first monomer and a second functional group obtained by removing one hydrogen atom from the second monomer. The hydrogel structure according to claim 5, which is formed by a crosslinking agent.
The cross-linked part is formed by a cross-linking agent having a plurality of functional groups of at least one of a third functional group and a fourth functional group, and the third functional group is represented by the following formula (1-1) or formula (1-2): The hydrogel structure according to claim 5, wherein the fourth functional group is a structure represented by the following formula (2).

(In Formula (1-1), R1 represents an alkyl group having 1 to 5 carbon atoms or hydrogen, R2 represents a methylene group, and * represents a bond. In Formula (1-2), R5 Represents a methylene group, * represents a bond, R3 represents a methylene group, R4 represents an alkyl group having 1 to 2 carbon atoms or hydrogen, and * represents a bond. Is shown.)
A method for producing a hydrogel structure according to any one of claims 1 to 7,
A preparation step of preparing a solution containing the first monomer, the second monomer, and a polymerization initiator for polymerizing and crosslinking the first monomer and the second monomer;
A method for producing a hydrogel structure, comprising a heating step of gelling by heating the solution.
The solution prepared in the preparation step includes at least one of a first functional group obtained by removing one hydrogen atom from the first monomer and a second functional group obtained by removing one hydrogen atom from the second monomer. The method for producing a hydrogel structure according to claim 8, further comprising a cross-linking agent having a plurality of functional groups.
The solution prepared in the preparation step further includes a crosslinking agent having a plurality of functional groups of at least one of a third functional group and a fourth functional group, wherein the third functional group is represented by the following formula (1-1) or formula ( The method for producing a hydrogel structure according to claim 8, wherein the structure is represented by 1-2), and the fourth functional group is a structure represented by the following formula (2).

(In Formula (1-1), R1 represents an alkyl group having 1 to 5 carbon atoms or hydrogen, R2 represents a methylene group, and * represents a bond. In Formula (1-2), R5 Represents a methylene group, * represents a bond, R3 represents a methylene group, R4 represents an alkyl group having 1 to 2 carbon atoms or hydrogen, and * represents a bond. Is shown.)
The method for producing a hydrogel structure according to any one of claims 8 to 10, wherein the preparation step and the heating step are performed in one pot.