KR20100118860A - Manufacturing method of biocompatible poly(vinyl alcohol)-based hydrogel - Google Patents

Abstract

PURPOSE: A manufacturing method of biocompatible poly(vinyl alcohol)-based hydrogel is provided to secure the harmlessness to the human body by avoid using a cross-linking agent without the toxicity. CONSTITUTION: A manufacturing method of biocompatible poly(vinyl alcohol)-based hydrogel comprises a step of freezing and melting a polyvinyl alcohol/hydrophilic polymer aqueous solution containing polyvinyl alcohol and a hydrophilic polymer. The weight average molecular weight of the polyvinyl alcohol is 10,000~1,000,000 g/mol. The freezing time for the freezing step is 1 second~12 hours.

Description

Manufacturing method of biocompatible poly (vinyl alcohol) -based hydrogel

The present invention relates to a method for producing a polyvinyl alcohol-based hydrogel having a very short production time, excellent mechanical properties, and excellent biocompatibility without using any organic solvents and crosslinking agents exhibiting human toxicity.

Hydrogel refers to a state in which a large amount of water is filled in a lattice of a polymer material to maintain a swelling, three-dimensional structure. The hydrogel may absorb at least 20% or more of the total weight of water, and among these, absorbing more than 95% of water is called a superabsorbent hydrogel. The hydrogel forms a structurally stable three-dimensional network structure with little fluidity due to external hysteresis, which is known to be formed by various factors such as covalent bonds, hydrogen bonds, van der Waals bonds, or physical aggregation. It is also thermodynamically stable after swelling in an aqueous solution, and has mechanical and physicochemical properties corresponding to the intermediate form of liquid and solid.

Since the development of hydrogels consisting of poly-2-hydroxyethyl methacrylate (PHEMA) by Wichterle et al. . Wichterle and D. Lim, Nature , 185 , 117 (1960).

Since the development of calcium alginate hydrogels in 1980, various biomaterials using natural or synthetic polymers have been developed, and various types of hydrogels have been developed as a result of many studies on the physical and chemical properties of hydrogels.

In addition, starting with the application of hygroscopic products based on superabsorbency, the present invention introduces a variety of additional functionalities for drug delivery systems, embolization, tissue engineering supports, chemical valves, and other proteins. , Bioreactors, sensors, chromatography, and cosmetic fillers, ranging from pharmaceutical applications to industrial applications. [SY Kim, Tissue Eng. Regen. Med., 5 , 14 (2008)].

Such hydrogels can be broadly classified into chemical hydrogels and physical hydrogels according to the crosslinking form of the polymers constituting them. Chemically cross-linked hydrogel by a radical polymerization (by polymerization of a low molecular weight monomer) or a cross-linked by chemical reaction, and a typical example, an ionic bond between the physical hydrogel polymer chains (for example, cross-linking of the alginate by Ca ²⁺⁾ or Hydrogels are formed through crosslinking by crystallization (crystallization by repeated freeze-thaw or crosslinking by increasing interchain interactions).

Polyvinyl alcohol (PVA), on the other hand, is non-toxicity, non-carcinogenicity, biodegradability, biocompatibility, excellent mechanical properties (high Its mechanical properties, high water content and other properties make it possible to deliver drug delivery systems, wound dressings, filler contact lenses, and biosensors. Research is being actively conducted for application to biomaterials such as.

The polyvinyl alcohol has also been used in the preparation of hydrogel physical or chemical crosslinking method.

The physical crosslinking method freezes the PVA aqueous solution without any additives for 12 to 24 hours under the freezing point of water (typically about -10 to -20 ° C), and again the temperature above the freezing point (typically Thawing at room temperature is repeated several times to form crosslinks or gels. However, this physical crosslinking method has a problem that it takes a long time usually 3 to 4 days or more by repeating the freezing and thawing process several times and the manufacturing process is somewhat complicated and the manufacturing efficiency is lowered.

Another chemical crosslinking method is crosslinking (hydrogel) by a crosslinking agent such as glutaraldehyde and boric acid. However, the crosslinking agents used in the chemical crosslinking method are most likely to be harmful to the human body, but it is difficult to use them as a material for applying to the human body since it is not easy to remove them completely from the hydrogel. There is a problem that the mechanical properties of the gel is somewhat low. Due to these problems, despite the excellent properties of polyvinyl alcohol hydrogels, the medical use of the hydrogels prepared from them is subject to considerable limitations.

Therefore, the present invention solves the problems of safety / property degradation due to the use of a human toxic crosslinking agent in the production of the conventional polyvinyl alcohol hydrogel by chemical crosslinking method, and problems such as productivity decrease due to a considerably long manufacturing time due to the physical crosslinking method. It is an object of the present invention to provide an improved method of preparing a polyvinyl alcohol-based hydrogel.

Therefore, an object of the present invention is to provide a manufacturing method that can be produced in a simple and short time to produce a polyvinyl alcohol-based hydrogel which is harmless to the human body and excellent in mechanical properties because it does not use a cross-linking agent having human toxicity.

In the present invention, a poly-vinyl alcohol solution may induce micro-separation of water molecules and polyvinyl alcohol to promote the formation of polyvinyl alcohol-rich domains (PVA-rich domain, a crosslinking role between polymer chains). The present invention was completed through numerous experiments that hydrophilic polymers were added and polyvinyl alcohol-based hydrogels having excellent mechanical properties could be formed by only one freeze-thaw process at an appropriate temperature and time.

Polyvinyl alcohol-based hydrogel manufacturing method according to the present invention, unlike the prior art does not use a cross-linking agent with human toxicity is excellent in biocompatibility, and also has the advantage of producing a hydrogel having excellent mechanical properties in a very short time There is this. Furthermore, the polyvinyl alcohol hydrogel prepared by the method of the present invention having such an advantage can be widely applied to the chemical field using polymers, and in particular, drug delivery system, embolization, tissue engineering scaffold, and other separation of proteins. And pharmaceutical applications such as concentration and stabilization, immunoassays, bioreactors, sensors, and cosmetic fillers.

The polyvinyl alcohol hydrogel production method for achieving the object of the present invention induces the micro-separation of water molecules and polyvinyl alcohol on the polyvinyl alcohol and polyvinyl alcohol aqueous solution polyvinyl alcohol rich region (PVA) -rich domain, a polyvinyl alcohol / hydrophilic polymer aqueous solution comprising a variety of hydrophilic polymers capable of promoting the formation of (crosslinking role between polymer chains) through a single freeze-thaw step at a temperature of 0 to -250 ℃ It is characterized by being manufactured.

Hereinafter, a method for preparing a polyvinyl alcohol hydrogel according to the present invention will be described in more detail.

In the polyvinyl alcohol hydrogel of the present invention, an aqueous solution is prepared by mixing a hydrophilic polymer with a predetermined ratio in an aqueous polyvinyl alcohol solution, freezing it at an appropriate temperature and time, and then defrosting it at room temperature by only one step. Are manufactured.

First, polyvinyl alcohol is dissolved in ultrapure water to prepare a polymer solution, and various hydrophilic polymers are mixed and used in this aqueous solution.

Preferably, the polyvinyl alcohol polymer has a weight average molecular weight of 1,000 to 1,000,000 g / mol.

The polyvinyl alcohol is preferably prepared in an aqueous solution of 1 to 40% by weight in ultrapure water (deionized water) is a solvent, more preferably 10 to 20% by weight. When the concentration of the polyvinyl alcohol solution is less than 1% by weight, there is a problem in that hydrogels having too weak physical properties are formed. When the concentration of the polyvinyl alcohol solution is greater than 40% by weight, the viscosity of the prepared solution is too high, making it difficult to handle. .

In addition, the hydrophilic polymer is preferably used by mixing 0.1 to 40% by weight in ultrapure water as a solvent, more preferably 5 to 30% by weight. When the hydrophilic polymer is used in less than 0.1% by weight, there is a problem that the polyvinyl alcohol produced is easily broken down due to the mechanical properties of the hydrogel, and when the hydrophilic polymer exceeds 40% by weight, the polymers are not uniformly mixed ( Precipitation formation) there is a problem that the hydrogel formed is produced unevenly.

Hydrophilic polymers that can promote the microphase separation of the polyvinyl alcohol used in the present invention include hyaluronic acid, alginic acid, pectin, and carrageenan (weight average molecular weight 1,000 to 5,000,000 g / mol). carrageenan, chondroitin sulfate, dextran sulfate, chitosan, polylysine, collagen, gelatin, carboxymethyl chitin, fibrin, dextran, agarose ), Pullulan, polyacrylamide (PAAm), poly (N-isopropyl acrylamide-co-acrylic acid) (P (NIPAAm-co-AAc)), poly (N-isopropyl acrylamide-co- Ethyl methacrylate) P (NIPAAm-co-EMA), polyvinylacetate / polyvinyl alcohol (PVAc / PVA), poly (N-vinyl pyrrolidone) (PVP), poly (methylmethacrylate-co-hydride Oxyethyl methacrylate) (P (MMA-co-HEMA)), poly (polyethylene glycol-co-peptide (P (PEG-c) o-peptide)), alginate-g- (polyethylene oxide-polypropylene oxide-polyethylene oxide) (alginate-g- (PEO-PPO-PEO)), poly (polylactic acid-co-glycolic acid) -co-serine (P (PLGA-co-serine)), collagen-acrylate, collagen-acrylate, alginate-acrylate, poly (hydroxypropyl methacrylamide-g-peptide) (P (HPMA- g-peptide)), poly (hydroxyethyl methacrylate / methgel) (P (HEMA / Matrigel)), hyaluronic acid-gN-isopropylacrylamide (HA-g-NIPAAm), polyethylene oxide (PEO), Polyethylene oxide-polypropylene oxide copolymer (PEO-PPO, Pluronic series), polyethylene oxide-polylactic acid copolymer (PEO-PLA), polyethylene oxide-polylactic glycolic acid copolymer (PEO-PLGA), polyethylene oxide-poly Caprolactone copolymer (PEO-PCL), polyoxyethylene alkyl ethers (Brij S eries, polyoxyethylene castor oil derivatives (Cremophores), polyoxyethylene sorbitan fatty acid esters (Tween Series), and polyoxyethylene stearates. One or more selected from the group consisting of can be used.

However, the present invention, in addition to the hydrophilic polymers set forth above, may have additional biocompatibility within the scope not departing from the object of the present invention, and may further include other hydrophilic polymers or additives that may produce the properties and effects required by the present invention. Of course.

In addition, in the preparation of a hydrogel using a polyvinyl alcohol and various hydrophilic polymer mixed aqueous solution of the present invention, the freezing conditions are hydro having excellent properties to be performed for 1 second to 12 hours at a temperature of 0 ℃ to -250 ℃ It is preferred to form a gel.

When the hydrophilic polymer is mixed with the polyvinyl alcohol aqueous solution as described above and frozen at the above temperature, the hydrophilic polymer induces micro-separation of water molecules and polyvinyl alcohol in the aqueous solution and thus the polyvinyl alcohol-rich region (PVA). -rich domain, which can promote the formation of crosslinks between polymer chains; three to four repeated freeze-thaw processes in the conventional physical crosslinking method. And it is possible to produce a hydrogel excellent in mechanical properties without using a crosslinking agent.

In more detail, when a polyethylene glycol, which is a kind of hydrophilic polymer, is mixed with an aqueous polyvinyl alcohol solution, polyvinyl alcohol chains are partially entangled or exist in a semi-crystallized state. Polyethylene glycol molecules are evenly dispersed in between. If the mixed aqueous solution is stored at room temperature (usually room temperature, room temperature) without freezing for a certain time, the polyvinyl alcohol rich region (PVA rich domain, Cross-linking role between polyvinyl alcohol) is formed, the density of the region is low so that the physical properties of the prepared hydrogel does not increase significantly.

This is similar to the phenomenon seen in the one-time freeze-thaw process of polyvinyl alcohol prepared through the conventional thawing-freezing process. Therefore, this process is repeated several times in the production of hydrogel through the conventional freeze-thawing process. By increasing the density of the polyvinyl alcohol rich region to prepare a polyvinyl alcohol hydrogel of excellent physical properties (usually takes 3 to 4 days).

However, in the case of the present invention, when the polyvinyl alcohol / hydrophilic polymer mixed aqueous solution is frozen at a temperature range of 0 ° C to -250 ° C, the hydrophilic polymer dissolved in the aqueous solution is micro-separation of water molecules and polyvinyl alcohol. Induces the formation of polyvinyl alcohol-rich domains (PVA-rich domain, the role of crosslinking between polymer chains), and 3-4 cycles of freeze-thaw, which is a typical physical crosslinking method, even through a single freeze-thaw process. Hydrogels having better physical properties than those performed are formed.

In addition, this effect is more pronounced as the content of the hydrophilic polymer mixed in the polyvinyl alcohol aqueous solution increases, but the content of the hydrophilic polymer is preferably used up to 40% by weight relative to the solvent (ultra pure water) content. If the content of the hydrophilic polymer exceeds 40% by weight with respect to the solvent (ultra pure water), there is a problem in that a hydrogel is produced non-uniformly produced because precipitation is formed or it is not uniformly mixed with polyvinyl alcohol.

Therefore, in the present invention, polyvinyl alcohol hydrogel having the desired physical properties and effects in only one process without requiring a long time that the freeze-thaw process has to be repeatedly performed three to four times as in the conventional physical crosslinking method. It is possible to manufacture.

The thawing of the polyvinyl alcohol hydrogel frozen at the predetermined temperature is preferably performed at a temperature of 1 ℃ to 50 ℃.

Figure 1 shows a schematic diagram of the manufacturing process of a polyvinyl alcohol hydrogel according to an embodiment of the present invention, by uniformly preparing a polyethylene glycol (PEG) of a hydrophilic polymer in a polyvinyl alcohol aqueous solution, and then the solution The hydrogel can be prepared by filling the mold into the desired shape and by only one freeze-thaw process at a suitable temperature and time.

Hereinafter, the present invention will be described in more detail with reference to the following examples, but the present invention is not limited thereto.

Example 1

Polyvinyl alcohol (weight average molecular weight 89,000 ~ 98,000 g / mol, hydrolysis ~ 98%) showing biocompatibility was added to deionized water and heated to 90 ° C. to prepare 15% by weight aqueous polyvinyl alcohol solution. Polyethylene glycol (PEG, weight average molecular weight 400 g / mol) was mixed in the ultrapure water to 10% by weight to prepare a polyvinyl alcohol / polyethylene glycol mixed aqueous solution.

The polyvinyl alcohol / polyethylene glycol was poured into a mixed aqueous solution on a frame and frozen at -196 ° C. for 1 minute and immediately thawed at room temperature for 4 hours, and the polyethylene glycol present in the formed hydrogel was purified in ultrapure water. Washing for 24 hours to prepare a polyvinyl alcohol hydrogel.

Example 2

Polyvinyl alcohol (weight average molecular weight 89,000 ~ 98,000 g / mol, hydrolysis ~ 98%) showing biocompatibility was added to deionized water and heated to 90 ° C. to prepare 15% by weight aqueous polyvinyl alcohol solution. Polyethylene glycol (PEG, weight average molecular weight 400 g / mol) was mixed in the ultrapure water to 20% by weight to prepare a polyvinyl alcohol / polyethylene glycol mixed aqueous solution.

The polyvinyl alcohol / polyethylene glycol was poured into a mixed aqueous solution on a frame and frozen at -196 ° C. for 1 minute and immediately thawed at room temperature for 4 hours, and the polyethylene glycol present in the formed hydrogel was purified in ultrapure water. Washing for 24 hours to prepare a polyvinyl alcohol hydrogel.

Example 3

Polyvinyl alcohol (weight average molecular weight 89,000 ~ 98,000 g / mol, hydrolysis ~ 98%) showing biocompatibility was added to deionized water and heated to 90 ° C. to prepare 15% by weight aqueous polyvinyl alcohol solution. Polyethylene glycol (PEG, weight average molecular weight 400 g / mol) was mixed to 30% by weight in the ultrapure water to prepare a polyvinyl alcohol / polyethylene glycol mixed aqueous solution.

The polyvinyl alcohol / polyethylene glycol was poured into a mixed aqueous solution on a frame and frozen at -196 ° C. for 1 minute and immediately thawed at room temperature for 4 hours, and the polyethylene glycol present in the formed hydrogel was purified in ultrapure water. Washing for 24 hours to prepare a polyvinyl alcohol hydrogel.

Example 4

A polyvinyl alcohol hydrogel was prepared using the same mixed aqueous solution and preparation as in Example 2, except that the mixture was frozen at a temperature of −70 ° C. for 60 minutes.

Example 5

A polyvinyl alcohol hydrogel was prepared using the same mixed aqueous solution and preparation as in Example 2, except that the mixture was frozen for 60 minutes at a temperature of −20 ° C.

Example 6

Polyvinyl alcohol (weight average molecular weight 89,000 ~ 98,000 g / mol, hydrolysis ~ 98%) showing biocompatibility was added to deionized water and heated to 90 ° C. to prepare 15% by weight aqueous polyvinyl alcohol solution. Alginic acid (Alginic acid, low viscosity, Sigma-Aldrich) was mixed to 2% by weight to prepare a polyvinyl alcohol / alginic acid mixed aqueous solution.

The polyvinyl alcohol / alginic acid mixed aqueous solution was poured into a frame and frozen at -196 ° C. for 1 minute, immediately thawed at room temperature for 4 hours, and the alginic acid present in the formed hydrogel was washed with excess ultrapure water for 24 hours to remove poly Vinyl alcohol hydrogel was prepared.

It can be observed that the shape and physical properties of the prepared polyvinyl alcohol hydrogel similar to Example 3.

Example 7

Polyvinyl alcohol (weight average molecular weight 89,000 ~ 98,000 g / mol, hydrolysis ~ 98%) showing biocompatibility was added to deionized water and heated to 90 ° C. to prepare 15% by weight aqueous polyvinyl alcohol solution. Hyaluronic acid (weight average molecular weight, 3,000 ~ 10,000 g / mol) was mixed to 5% by weight to prepare a polyvinyl alcohol / hyaluronic acid mixed aqueous solution.

The polyvinyl alcohol / hyalonic acid mixed aqueous solution was poured into a frame and frozen at -196 ° C. for 1 minute and immediately thawed at room temperature for 4 hours. The hyaluronic acid present in the formed hydrogel was added in an excessive amount of ultrapure water to 24 hours. Washing for a time to prepare a polyvinyl alcohol hydrogel.

Comparative Example 1

Polyvinyl alcohol (weight average molecular weight 89,000 ~ 98,000 g / mol, hydrolysis ~ 98%) showing biocompatibility was put in deionized water and heated to 90 ℃ to prepare a 15% by weight polyvinyl alcohol aqueous solution.

The polyvinyl alcohol aqueous solution was poured into a frame and frozen at -20 ° C for 18 hours and thawed at 25 ° C for 4 hours to prepare a polyvinyl alcohol hydrogel (once freeze-thaw).

Comparative Example 2

Polyvinyl alcohol (weight average molecular weight 89,000 ~ 98,000 g / mol, hydrolysis ~ 98%) showing biocompatibility was put in deionized water and heated to 90 ℃ to prepare a 15% by weight polyvinyl alcohol aqueous solution.

The polyvinyl alcohol aqueous solution was poured into a frame and frozen at −196 ° C. for 1 minute and thawed at 25 ° C. for 4 hours to prepare a polyvinyl alcohol hydrogel (once freeze-thaw).

Comparative Example 3

Polyvinyl alcohol (weight average molecular weight 89,000 ~ 98,000 g / mol, hydrolysis ~ 98%) showing biocompatibility was put in deionized water and heated to 90 ℃ to prepare a 15% by weight polyvinyl alcohol aqueous solution.

The polyvinyl alcohol aqueous solution was poured into a frame and frozen at 18 ° C. for 18 hours, and thawed at 25 ° C. for 4 hours. The polyvinyl alcohol hydrogel was prepared by repeating the freeze-thaw process three times under the same conditions (conventional freeze-thaw method; LOZINSKY VL et al., J. Appl. Polymer Sci., 77 , 2017-2023 (2000) ).

Comparative Example 4

A polyvinyl alcohol hydrogel was prepared using the same mixed aqueous solution as Example 2, except that the sample was stored at room temperature (25 ° C.) for 24 hours without a freezing process.

Experimental Example

Mechanical properties of the hydrogels based on the polyvinyl alcohols prepared in Examples and Comparative Examples were performed as follows, and the results are shown in Table 1 below.

Mechanical Properties: Dumbbell-shaped specimens were prepared using ASTM D638 (type V), and then tensile strength was measured at a rate of 50 mm / min cross-head.

Tensile Strength (KPa) Example 1 328 ± 93 Example 2 1300 ± 32 Example 3 1798 ± 134 Example 4 1330 ± 57 Example 5 1310 ± 90 Example 6 1852 ± 82 Example 7 1951 ± 78 Comparative Example 1 Not measurable (gel formation difficult) Comparative Example 2 125 ± 67 Comparative Example 3 345 ± 52 Comparative Example 4 238 ± 93

As shown in the results of Table 1, as shown in the embodiment of the present invention, a hydrophilic polymer having biocompatibility is mixed with polyvinyl alcohol, and the hydrophilic polymer exhibits excellent mechanical properties by only one freeze-thaw process at an appropriate temperature and time. It could be confirmed that the gel could be prepared.

In addition, as the content of the hydrophilic polymer is increased (Examples 1, 2, 3) it can be confirmed that the mechanical properties are excellent, which means that the polyethylene glycol in the polyvinyl alcohol hydrogel is fine of water molecules and polyvinyl alcohol It is believed that the phase separation is promoted, and thus, more polyvinyl alcohol (PVA rich region, crosslinking role between polyvinyl alcohol chains) is formed in proportion to the amount of polyethylene glycol added.

However, in the case of polyvinyl alcohol hydrogels prepared by freezing at -20 ° C (Comparative Example 1) and -196 ° C (Comparative Example 2) with only polyvinyl alcohol aqueous solution and thawing at room temperature (single freeze-thaw), It was confirmed that the physical properties are significantly lower than the embodiment of the present invention, through which only one freeze-thaw using polyvinyl alcohol aqueous solution was able to confirm the difficulty of preparing a polyvinyl alcohol hydrogel having excellent properties. . As reported, the physical properties were also enhanced by increasing the number of freeze-thaw processes of the polyvinyl alcohol solution (Comparative Example 4).

As mentioned above, when the polyvinyl alcohol / polyethylene glycol aqueous solution is stored for a certain time at room temperature (meaning room temperature, room temperature) without a freezing process, it is due to the interaction between the polyvinyl alcohol chains (hydrogen bond, etc.). Although the physical properties of the polyvinyl alcohol-rich region were enhanced, the physical properties of the polyvinyl alcohol hydrogels were significantly lower than those of the frozen material at the temperature of the present invention. This could be confirmed (Comparative Example 4).

From this, the hydrogel based on polyvinyl alcohol according to the present invention is capable of producing a hydrogel having excellent mechanical properties through only one freeze-thawing process in a very short time without using any chemical crosslinking agent that is harmful to the human body. It is a very positive and highly applicable hydrogel for applying polyvinyl alcohol hydrogel in the field of tissue engineering by providing a possible method.

1 is a schematic diagram showing a manufacturing process of a polyvinyl alcohol hydrogel according to the present invention.

Claims (7)

A method of preparing a polyvinyl alcohol hydrogel comprising the step of freeze-thawing a polyvinyl alcohol / hydrophilic polymer aqueous solution comprising polyvinyl alcohol and a hydrophilic polymer at 0 ° C. to −250 ° C. once. The method according to claim 1, wherein the polyvinyl alcohol has a weight average molecular weight of 10,000 to 1,000,000 g / mol. The method of claim 1, wherein the polyvinyl alcohol is contained in a concentration of 1 to 40% by weight, and the hydrophilic polymer is prepared in a polyvinyl alcohol hydrogel, characterized in that it is contained in a concentration of 0.1 to 40% by weight. The method of claim 1, wherein the freezing time is 1 second to 12 hours. The method of claim 1, wherein the hydrophilic polymer is hyaluronic acid, alginic acid, pectin, carrageenan, chondroitin sulfate, dextran sulfate, chitosan, Polylysine, collagen, gelatin, carboxymethyl chitin, fibrin, dextran, agarose, pullulan, polyacrylamide (PAAm), poly (N-isopropyl) Acrylamide-co-acrylic acid) (P (NIPAAm-co-AAc)), poly (N-isopropyl acrylamide-co-ethylmethacrylate) P (NIPAAm-co-EMA), polyvinylacetate / polyvinyl alcohol (PVAc / PVA), poly (N-vinyl pyrrolidone) (PVP), poly (methylmethacrylate-co-hydroxyethyl methacrylate) (P (MMA-co-HEMA)), poly (polyethylene glycol -co-peptide (P (PEG-co-peptide)), alginate-g- (polyethylene oxide-polypropylene oxide-polyethylene oxime (Alginate-g- (PEO-PPO-PEO)), poly (polylactic acid-co-glycolic acid) -co-serine) (P (PLGA-co-serine)), collagen-acrylate (collagen- acrylate), alginate-acrylate, poly (hydroxypropyl methacrylamide-g-peptide) (P (HPMA-g-peptide)), poly (hydroxyethyl methacrylate / methgel) ( P (HEMA / Matrigel)), hyaluronic acid-gN-isopropylacrylamide (HA-g-NIPAAm), polyethylene oxide (PEO), polyethylene oxide-polypropylene oxide copolymer (PEO-PPO, Pluronic series), polyethylene oxide Polylactic acid copolymer (PEO-PLA), polyethylene oxide-polylactic glycolic acid copolymer (PEO-PLGA), polyethylene oxide-polycaprolactone copolymer (PEO-PCL), polyoxyethylene alkyl ethers ethers, Brij Series), polyoxyethylene castor oil derivatives (Cremophores), Preparation of polyvinyl alcohol hydrogel, characterized in that at least one selected from the group consisting of polyoxyethylene sorbitan fatty acid esters (Tween Series), polyoxyethylene stearates, etc. Way. The method of claim 1, wherein the hydrophilic polymer induces micro-separation of water molecules and polyvinyl alcohol in the aqueous polyvinyl alcohol solution to promote formation of a polyvinyl alcohol rich domain. Method for producing a polyvinyl alcohol hydrogel, characterized in that. The method of claim 1, wherein the thawing is carried out at a temperature of 1 to 50 ℃ polyvinyl alcohol hydrogel production method.

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