CN110643055A

CN110643055A - Hydrogel and preparation method thereof, and biological membrane fixing device and application

Info

Publication number: CN110643055A
Application number: CN201910951778.3A
Authority: CN
Inventors: 李锐聪; 谭睿哲; 梁丽金; 邹鹏; 陈琦
Original assignee: Ningbo Rui Biotechnology Co Ltd
Current assignee: Ningbo Rui Biotechnology Co Ltd
Priority date: 2019-10-08
Filing date: 2019-10-08
Publication date: 2020-01-03

Abstract

The invention provides a hydrogel and a preparation method thereof, a biological membrane fixing device and application, and relates to the technical field of biological materials. The hydrogel comprises the following raw materials: synthesizing monomers, a solubilizer, a cross-linking agent, an initiator, a catalyst and water; the synthetic monomers comprise HEMA and/or derivatives of HEMA; the dosage of each raw material is as follows according to the mass ratio of the raw materials to water: synthesizing monomers: water is (0.5-20): 1; solubilizer: water is (0.1-10): 1; a crosslinking agent: water is (0.001-0.5): 1; initiator: water is (0.05-2): 1; catalyst: water is (0.05-2): 1. the hydrogel has good biocompatibility, stability and hydrophilicity; good water absorption swelling performance; good optical performance; and has strong mechanical property and soft texture. The biomembrane fixing device prepared from the hydrogel has small foreign body sensation and is comfortable to wear.

Description

Hydrogel and preparation method thereof, and biological membrane fixing device and application

Technical Field

The invention relates to the technical field of biological materials, in particular to hydrogel and a preparation method, a biological membrane fixing device and application thereof.

Background

The biofilm currently used for ocular surface damage treatment is primarily amniotic membrane, but also includes other membranes with cells. With the continuous research on the biology and chemistry of the amnion, the amnion as the last basement membrane layer of the human body has shown a great clinical application value. The amnion is used as an important support, and can restore the normal epithelial phenotype of cornea and conjunctiva, promote the migration of epithelial cells, strengthen the adhesion of epithelium and a basal layer, promote the differentiation of epithelial cells and inhibit the apoptosis of epithelial cells. However, the existing amnion covering and amnion transplanting operations mostly use a suture method, the amnion fixing mode inevitably wounds the ocular surface, the suture process is easy to cause damage of the amnion or other biological membranes, and the replacement of the amnion and other biological membranes is not facilitated. At present, metals (such as nickel-titanium alloy, silver and the like) and organic glass are used as a biomembrane fixing device on the market, and although the materials have good supporting effect and high hardness and are not easy to deform, the materials have obvious foreign body sensation, are easy to cause discomfort in wearing and the biomembrane is displaced and cannot well play a role in fixing. Therefore, an improved material capable of serving as a biofilm immobilization device is needed in the market.

In view of the above, the present invention is particularly proposed.

Disclosure of Invention

The first purpose of the present invention is to provide a hydrogel having good biocompatibility, mechanical properties and hydrophilicity.

The second object of the present invention is to provide a method for producing the above hydrogel.

The third object of the present invention is to provide a biofilm immobilization device, which is mainly prepared from the above hydrogel or prepared by the above preparation method.

The fourth purpose of the invention is to provide the hydrogel, the preparation method of the hydrogel or the application of the biological membrane fixing device in the preparation of medical products.

In order to solve the technical problems, the invention adopts the following technical scheme:

according to one aspect of the present invention, there is provided a hydrogel comprising, as raw materials: synthesizing monomers, a solubilizer, a cross-linking agent, an initiator, a catalyst and water; the synthetic monomers comprise HEMA and/or derivatives of HEMA; the dosage of each raw material is as follows according to the mass ratio of the raw materials to water:

synthesizing monomers: water is (0.5-20): 1;

solubilizer: water is (0.1-10): 1;

a crosslinking agent: water is (0.001-0.5): 1;

initiator: water is (0.05-2): 1;

catalyst: water is (0.05-2): 1.

according to another aspect of the present invention, the present invention further provides a preparation method of the hydrogel, comprising mixing the synthetic monomer, the solubilizer, the cross-linking agent, the initiator, the catalyst and the water according to the formula amount, and reacting to obtain the hydrogel.

According to another aspect of the present invention, there is also provided a biofilm immobilization device which is mainly prepared from the above hydrogel or the above preparation method.

According to another aspect of the present invention, there is also provided the use of the above hydrogel or the above hydrogel preparation method for the preparation of a medical product.

Compared with the prior art, the invention has the following beneficial effects:

the hydrogel provided by the invention takes hydroxyethyl methacrylate (HEMA) and/or a derivative of hydroxyethyl methacrylate as a base material, and the preparation raw materials further comprise a solubilizer, a cross-linking agent, an initiator, a catalyst and water. By reasonably proportioning the dosage of each raw material, the obtained hydrogel has the following advantages: (1) good biocompatibility and stability; (2) good water absorption swelling performance; (3) good optical performance and strong mechanical property, and soft texture; (4) the hydrogel has good hydrophilicity, can reduce the adhesion and deposition of protein substances on the hydrogel, and relieves the problem of easy bacterial breeding caused by the adhesion and deposition of protein. The preparation method of the hydrogel provided by the invention is simple to operate and is suitable for wide application.

The biological membrane fixing device provided by the invention is mainly prepared from the hydrogel or the preparation method. The biological film is pasted on the affected part through the hydrogel part contained in the biological film fixing device, so that the secondary wound caused by sewing the biological film on the affected part can be avoided. The hydrogel has good water-absorbing swelling property, flexibility and biocompatibility, so that the biomembrane fixing device has small foreign body sensation and is comfortable to wear. Meanwhile, the hydrogel has good hydrophilicity, so that the problem that bacteria are easy to breed caused by adhesion and deposition of protein can be solved.

The hydrogel has good biocompatibility, water absorption, mechanical property and hydrophilic property, and can be widely used for preparing stents, dressings or various medical materials needing to be placed in vivo. The hydrogel is used for preparing medical products, has good flexibility and low foreign body sensation, and can effectively avoid the problem of easy bacterial breeding caused by adhesion and deposition of protein.

Drawings

In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings used in the description of the embodiments or the prior art will be briefly described below, and it is obvious that the drawings in the following description are some embodiments of the present invention, and other drawings can be obtained by those skilled in the art without creative efforts.

FIG. 1 is a view showing the shape of a biofilm fixing device for fixing a biofilm of ocular surface injury according to the present invention;

FIG. 2 is a contact angle of a hydrogel provided in example 1 of the present invention;

FIG. 3 is a contact angle of the hydrogel provided in example 2 of the present invention.

Detailed Description

The technical solutions of the present invention will be described clearly and completely with reference to the following embodiments, and it should be understood that the described embodiments are some, but not all, embodiments of the present invention. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.

synthesizing monomers: water is (0.5-20): 1, for example, can be, but is not limited to, 0.5:1, 1:1, 2:1, 5:1, 8:1, 10:1, 12:1, 15:1, 50:3, 18:1, or 20: 1;

solubilizer: water is (0.1-10): 1, for example, can be, but is not limited to, 0.1:1, 0.5:1, 1:1, 2:1, 3:1, 10:3, 4:1, 5:1, 6:1, 7:1, 8:1, 9:1, or 10: 1;

a crosslinking agent: water is (0.001-0.5): 1, for example, but not limited to, 0.001:1, 0.01:1, 0.1:1, 0.2:1, 0.3:1, 0.4:1, or 0.5: 1;

initiator: water is (0.05-2): 1, for example, but not limited to, 0.05:1, 0.1:1, 1:3, 0.5:1, 2:3, 1:1, 1.5:1, or 2: 1;

catalyst: water is (0.05-2): 1, for example, can be, but is not limited to, 0.05:1, 0.1:1, 1:3, 0.5:1, 2:3, 1:1, 1.5:1, or 2: 1.

The hydrogel synthesized by the polyhydroxyethyl methacrylate (HEMA) or the derivative thereof has good biocompatibility and controllable mechanical property; by optimizing the proportion of the synthetic monomer, the solubilizer, the cross-linking agent, the initiator, the catalyst and the water, the mechanical property, the contact angle and the water absorption rate of the hydrogel can be optimized to improve the hydrophilicity of the material, so that the anti-adhesion property of the hydrogel is increased, and the biological material which is more hydrophilic and has weaker cell adhesion capability is obtained. The hydrogel of the invention has the following advantages: (1) good biocompatibility and stability; (2) good water absorption swelling performance; (3) good optical performance and strong mechanical property, and soft texture; (4) the hydrogel has good hydrophilicity, can reduce the adhesion and deposition of protein substances on the hydrogel, and relieves the problem of easy bacterial breeding caused by the adhesion and deposition of protein.

The synthetic monomer in the hydrogel provided by the invention comprises HEMA and/or HEMA derivatives, wherein the structural formula of HEMA is shown as (i):

in some alternative embodiments, derivatives of HEMA include HEMA functionalized derivatives to optimize the quality of the hydrogel after reaction, or to improve the efficiency of the reaction, etc. In the functionalized derivatives, the derivatized functional group preferably comprises-CH₃、-CHO、-COOH、-NH₂And cyclodextrin.

Wherein the formula of the — CHO functional group derivative is preferably as shown in (ii):

-NH₂the structural formula of the functional group derivative is preferably as shown in (iii):

the formula of the derivative of the-COOH function is preferably as shown in (iv):

-CH₃the structural formula of the functional group derivative is preferably as shown in (v):

in some preferred embodiments, the crosslinking agent comprises a crosslinking agent comprising allyl reactive units, wherein the crosslinking agent comprising allyl reactive units preferably comprises at least one of polyethylene glycol diacrylate, ethylene glycol dimethacrylate, and triallyl isocyanurate; in some specific embodiments, optionally, the crosslinker comprises polyethylene glycol diacrylate; optionally, the crosslinker comprises ethylene glycol dimethacrylate; optionally, the crosslinking agent comprises triallyl isocyanurate; optionally, the crosslinker comprises polyethylene glycol diacrylate and ethylene glycol dimethacrylate; optionally, the crosslinking agent comprises ethylene glycol dimethacrylate and triallyl isocyanurate. In some preferred embodiments, ethylene glycol dimethacrylate is more effective as a cross-linking agent.

In some preferred embodiments, the initiator may be selected from a photoinitiator or a thermal initiator.

The photoinitiator includes but is not limited to at least one of 2-hydroxy-2-methyl propiophenone, ethyl 2,4, 6-trimethylbenzoylphosphonate and ethyl 2,4, 6-trimethylbenzoylphosphonate; in some specific embodiments, optionally including 2-hydroxy-2-methylpropiophenone; optionally 2,4, 6-trimethylbenzoylphosphonic acid ethyl ester; optionally 2,4, 6-trimethylbenzoylphosphonic acid ethyl ester; optionally 2-hydroxy-2-methylpropiophenone and ethyl 2,4, 6-trimethylbenzoylphosphonate; optionally including ethyl 2,4, 6-trimethylbenzoylphosphonate and ethyl 2,4, 6-trimethylbenzoylphosphonate.

The thermal initiator preferably includes an azo-type initiator or a peroxide-type initiator. The azo-type initiator preferably includes azobisisobutyronitrile. The peroxide initiator optionally includes at least one of benzoyl peroxide, benzoyl t-butyl peroxide, and methyl ethyl ketone peroxide. In some particular embodiments, optionally, the peroxide initiator comprises benzoyl peroxide; alternatively, the peroxide initiator comprises benzoyl tert-butyl peroxide; alternatively, the peroxide initiator comprises methyl ethyl ketone peroxide; alternatively, the peroxide initiator comprises benzoyl peroxide and benzoyl tert-butyl peroxide. The peroxide initiator optionally comprises a persulfate-type thermal initiator, specific examples of which include ammonium persulfate and/or potassium persulfate, with ammonium persulfate preferably being used.

In some preferred embodiments, the catalyst comprises a fatty amine catalyst, preferably comprising N, N' -tetramethylethylenediamine.

In some preferred embodiments, the solubilizing agent comprises a polyol, preferably glycerol.

The biocompatibility, stability, water absorbability, optical property, hydrophilicity and the like of the hydrogel can be further optimized by optimizing the proportion of the raw materials for preparing the hydrogel.

In some preferred embodiments, the amounts of each raw material are as follows, in terms of the mass ratio of each raw material to water:

synthesizing monomers: water is (5-20): 1;

solubilizer: water is (1-5): 1;

a crosslinking agent: water is (0.01-0.1): 1;

initiator: water is (0.1-1): 1;

catalyst: water is (0.1-1): 1.

in some more preferred embodiments, the amounts of each raw material are as follows, in terms of the mass ratio of each raw material to water:

synthesizing monomers: water is 50: 3;

solubilizer: the ratio of water is 10: 3;

a crosslinking agent: the ratio of water is 1: 15;

initiator: the ratio of water is 2: 3;

catalyst: the ratio of water is 2: 3;

in some preferred embodiments, the synthetic monomer is HEMA; the solubilizer is glycerol; the cross-linking agent is ethylene glycol dimethacrylate; the initiator is ammonium persulfate; the catalyst is N, N, N ', N' -tetramethyl ethylenediamine.

According to another aspect of the present invention, there is also provided a method for preparing the above hydrogel, comprising mixing a synthetic monomer, a solubilizer, a crosslinking agent, an initiator, a catalyst and water, and reacting to obtain the hydrogel. The preparation method is simple to operate and is suitable for wide application.

In some preferred embodiments, the above raw materials are mixed and reacted at 20 to 100 ℃, and the reaction temperature may be, for example, but not limited to, 20 ℃, 30 ℃, 40 ℃, 50 ℃, 60 ℃, 70 ℃, 80 ℃, 90 ℃ or 100 ℃, preferably at 50 to 60 ℃, and more preferably at 60 ℃. The reaction time is preferably 12-48 h, for example, but not limited to, 12h, 16h, 20h, 24h, 30h, 36h, 40h or 48 h; the reaction is preferably carried out for 24 hours.

In some preferred embodiments, the preparation method further comprises removing unreacted materials, including unreacted synthetic monomers, initiators, catalysts and the like, in the hydrogel obtained after the reaction, so as to avoid side effects of the unreacted residues on a used object in use. The hydrogel is preferably soaked in ethanol and/or water, either alone or in an aqueous solution of ethanol to remove unreacted materials. Among them, the hydrogel is preferably soaked in an ethanol solution with a mass concentration of 25% to 35%, for example, but not limited to, 25%, 28%, 30%, 32% or 35%, and the mass concentration refers to the mass ratio of ethanol to ethanol solution in the ethanol solution, and more preferably 30%, and the effect of removing unreacted components after soaking is better. The soaking time is preferably 2-5 days, and more preferably 3 days.

In some preferred embodiments, the hydrogel from which unreacted substances are removed is dried to obtain a dry hydrogel, wherein the drying is preferably performed by vacuum drying, and the drying time is preferably 12 to 36 hours, and may be, for example, but not limited to, 12 hours, 13 hours, 14 hours, 15 hours, 16 hours, 17 hours, 18 hours, 19 hours, 20 hours, 21 hours, 22 hours, 23 hours, 24 hours, 25 hours, 26 hours, 27 hours, 28 hours, 29 hours, 30 hours, 31 hours, 32 hours, 33 hours, 34 hours, 35 hours, or 36 hours, and is preferably 24 hours.

In some preferred embodiments, the synthetic monomer, solubilizer, cross-linking agent, initiator, catalyst and water are mixed and placed in a mold, and then reacted to obtain a predetermined shape, so as to facilitate further processing into various products, or directly form the desired shape of the product by molding of the mold.

In some preferred embodiments, the preparation method comprises the steps of:

(a) mixing a synthetic monomer, a solubilizer, a cross-linking agent, an initiator, a catalyst and water, and then placing the mixture into a mold;

(b) reacting the die in the step (a) for 24 hours at the temperature of 20-100 ℃, and curing and forming;

(c) taking out the formed hydrogel, soaking and washing the formed hydrogel for 3 days by using an ethanol solution with the mass concentration of 30% to remove unreacted monomers, an initiator and a catalyst in a sample;

(d) vacuum drying for 24h to obtain the dry hydrogel.

According to another aspect of the present invention, there is also provided a biofilm immobilization device which is mainly prepared from the above hydrogel or mainly prepared by the above preparation method. The biological film fixing device is a device for fixing the biological film on an affected part, and the biological film is mainly pasted on the affected part through the hydrogel part contained in the biological film fixing device, so that secondary wound caused by sewing the biological film on the affected part is avoided. The hydrogel has good water-absorbing swelling property, flexibility and biocompatibility, so that the biomembrane fixing device has small foreign body sensation and is comfortable to wear. Meanwhile, the hydrogel has good hydrophilicity, so that the problem that bacteria are easy to breed caused by adhesion and deposition of protein can be solved.

The hydrogel provided by the invention can be directly used for further processing into a biological membrane fixing device; or the biological membrane fixing device is prepared by adopting the preparation method, for example, the hydrogel is prepared into the shape of the biological membrane fixing device or the shapes of some parts in the biological membrane fixing device by adopting a mould containing the shape of the biological membrane fixing device or a mould containing the shape of some parts in the biological membrane fixing device. The biological membrane that can be fixed by the biological membrane fixing device provided by the invention is preferably amnion.

In some preferred embodiments, the biofilm fixing device is used for fixing a biofilm for treating ocular surface injury, and the contact surface of the biofilm fixing device for fixing the ocular surface injury and the surface of the eyeball is in a ring shape with a radian, such as a contact lens, and the radian is matched with the radian of the surface of the eyeball, so that the biofilm fixing device can cover the surface of the eyeball with the biofilm. The biological membrane can be matched with the radian of the surface of the eyeball, can be matched with the radian of the whole eyeball surface or the radian of part of the surface of the eyeball, and can be applied to an affected part on the surface of the eyeball. When the biomembrane fixing device is used, the annular hydrogel part covers the periphery of the biomembrane, the biomembrane is pasted on the injury part of the ocular surface and can be directly placed on the ocular surface of a patient, and the biomembrane can be effectively and conveniently attached and fixed on the surface of an eyeball without surgical suture due to the excellent water absorption swelling property and softness of the hydrogel.

According to another aspect of the present invention, there is also provided the use of the above hydrogel or the above hydrogel preparation method for the preparation of a medical product. The hydrogel has good biocompatibility, water absorption, mechanical property and hydrophilic property, and can be widely used for preparing stents, dressings or various medical materials needing to be placed in vivo. The hydrogel is used for preparing medical products, has good flexibility and low foreign body sensation, and can effectively avoid the problem of easy bacterial breeding caused by adhesion and deposition of protein. For example, in some embodiments, the medical product comprises a biofilm immobilization device prepared using the hydrogel described above or the method of preparation described above; or the amnion and the biological membrane fixing device are combined into a medical product for repairing ocular surface injury, and the medical product is simple to implant, comfortable to wear, free of secondary wound and good in repairing effect.

The technical solution and the advantages of the present invention will be further explained with reference to the preferred embodiments.

Wherein the polypropylene molds used in examples 1 to 10 and comparative examples 1 to 2 make the shaped hydrogel have a ring shape and fit to the surface of the eyeball, and the dried hydrogel in a dry state can be directly used for fixing a biofilm applied to the ocular surface as a biofilm fixing device for fixing a biofilm damaged on the ocular surface. The polypropylene molds used in examples 1 to 10 and comparative examples 1 to 2 were shaped into the hydrogel having a shape shown in FIG. 1.

Example 1

This example provides a hydrogel, and the amounts of the raw materials, in terms of the mass ratio of the raw materials to water, are as follows:

HEMA: water is 50: 3;

solubilizer: the ratio of water is 5: 1;

a crosslinking agent: the ratio of water is 1: 10;

initiator: the ratio of water is 2: 3;

catalyst: the ratio of water is 1: 3.

Wherein, the solubilizer is glycerol, the cross-linking agent is polyethylene glycol diacrylate, the initiator is ammonium persulfate, and the catalyst is N, N, N ', N' -tetramethyl ethylenediamine.

The preparation method comprises the following steps:

(1) fully stirring and uniformly mixing HEMA, glycerol, water, a cross-linking agent, an initiator and a catalyst, and injecting into a polypropylene mould;

(2) putting the injected polypropylene mould into a 60 ℃ oven, reacting for 24 hours, and curing and molding;

(3) taking out the formed hydrogel, soaking and washing the hydrogel for 3 days by using an ethanol aqueous solution (the mass ratio of ethanol to water is 3: 7, so that the mass concentration of ethanol is 30 percent) to remove unreacted monomers, an initiator and a catalyst in a sample;

(4) vacuum drying for 24h to obtain dry pHEMA hydrogel.

The contact angle of the hydrogel is shown in FIG. 1, and the contact angle is 56. + -. 3.4 ℃.

Example 2

HEMA: water is 50: 3;

solubilizer: the ratio of water is 10: 3;

a crosslinking agent: the ratio of water is 1: 15;

initiator: the ratio of water is 2: 3;

catalyst: the ratio of water is 2: 3.

Wherein the solubilizer is glycerol, the cross-linking agent is ethylene glycol dimethacrylate, the initiator is ammonium persulfate, and the catalyst is N, N, N ', N' -tetramethyl ethylenediamine.

The preparation method comprises the following steps:

(2) putting the injected polypropylene mould into a 50 ℃ oven, reacting for 24 hours, and curing and molding;

(4) vacuum drying for 24h to obtain dry pHEMA hydrogel.

The contact angle of the hydrogel is shown in FIG. 2, and the contact angle is 54. + -. 2.1 ℃.

Example 3

HEMA: water is 0.5: 1;

solubilizer: water is 10: 1;

a crosslinking agent: water is 0.001: 1;

initiator: the ratio of water is 2: 1;

catalyst: the ratio of water is 0.05: 1.

Wherein the solubilizer is glycerol, the cross-linking agent is ethylene glycol dimethacrylate, the initiator is ammonium persulfate, and the catalyst is N, N, N ', N' -tetramethylethylenediamine, and the preparation method is the same as that in example 2.

Example 4

HEMA: the ratio of water is 20: 1;

solubilizer: water is 0.1: 1;

a crosslinking agent: water is 0.5: 1;

initiator: water 0.05: 1;

catalyst: the ratio of water is 2: 1.

Example 5

HEMA: the ratio of water is 20: 1;

solubilizer: 1:1 of water;

a crosslinking agent: water is 0.1: 1;

initiator: water is 0.1: 1;

catalyst: the ratio of water is 1: 1.

Example 6

HEMA: the ratio of water is 5: 1;

solubilizer: the ratio of water is 5: 1;

a crosslinking agent: water is 0.01: 1;

initiator: 1:1 of water;

catalyst: the ratio of water is 0.1: 1.

Example 7

This example differs from example 2 in that: the synthetic monomer is a functionalized derivative of HEMA, methylated HEMA is used as the synthetic monomer, and the structural formula is shown as (v):

example 8

This example differs from example 2 in that: the cross-linking agent is triallyl isocyanurate, and the initiator is azodiisobutyronitrile.

Example 9

This example differs from example 2 in that: in the step (2), the injected polypropylene mould is put into an oven with the temperature of 20 ℃, reacted for 24 hours, cured and molded.

Example 10

This example differs from example 2 in that: in the step (2), the injected polypropylene mould is put into an oven with the temperature of 100 ℃, reacted for 24 hours, cured and molded.

Comparative example 1

This comparative example provides a material that differs from example 1 in that: the water-soluble paint does not contain a solubilizer, and the dosage of each raw material is as follows according to the mass ratio of each raw material to water:

HEMA: water is 25: 1;

a crosslinking agent: water is 0.001: 1;

initiator: the ratio of water is 3: 1;

catalyst: the ratio of water is 0.05: 1.

Comparative example 2

This comparative example provides a material that differs from example 1 in that: the dosage of each raw material is as follows according to the mass ratio of the raw materials to water:

synthesizing monomers: water 0.5: 1;

solubilizer: the water content is 15: 1;

a crosslinking agent: water was 0.001: 1;

initiator: water was 0.001: 1;

catalyst: water 2.5: 1.

comparative example 3

Commercially available products under the product name Acuvue Oasys; the manufacturer is Johnson & Johnson Vision Care; the commercial product is Senofilcon A, synthesized primarily from the monomers MPDMS, DMA, HEMA, siloxane macro, TEGDMA and PVP.

Comparative example 4

A commercially available product under the product name purevision acuvue Oasys; the manufacturer is Bausch & Lomb; the commercial product is Balafilcon A, which is mainly synthesized from monomers NVP, TPVC, NVA and PBVC.

Effect example 1

Cytotoxicity (verification of Material safety)

According to GB/T16886.5-2003 section 5 of biological evaluation of medical devices: in vitro cytotoxicity test the method recommended in vitro cytotoxicity test "was used to evaluate the risk of toxicity caused by the sample. The cytotoxicity response was graded as shown in table 1, and the experimental results are shown in table 2.

TABLE 1 grading of cytotoxic reactions

TABLE 2 results of cytotoxicity experiments

Effect example 2

Contact Angle test (i.e., hydrophilicity test)

The surface water contact angle is an important factor for evaluating the hydrophilicity and hydrophobicity of the material surface, and the static water contact angle of the hydrogel sample of each example in the air is measured by a CAM-PLUS contact angle determinator (TANTEC, Germany). The swollen hydrogels were first cut into 10mm × 10mm thin slices, frozen in liquid nitrogen and dried with a freeze dryer, and finally the dried samples were stained on a glass slide with a double-sided tape, 5 μ L of water droplets were directly dropped on the surface of each sample, and then the value of the contact angle was directly read from the image of the water droplets. The contact angle was measured for each sample at 5 different positions and averaged. Preferred embodiment contact angles refer to fig. 2 and 3.

Table 3 contact angle test results

Group of	Contact angle
		Example 1	52±2.6°
Example 2	54±2.1°
		Example 3	43±2.3°
Example 4	61±2.1°
		Example 5	66±2.1°
Example 6	49±2.7°
		Example 7	64±2.3°
Example 8	61±2.5°
		Example 9	59±2.3°
Example 10	65±2.2°
		Comparative example 1	73±2.6°
Comparative example 2	78±2.1°
		Comparative example 3	80.0±0.8°
Comparative example 4	86.5±0.9°

Effect example 3

The absorbance of the sample at 550nm was measured in an ultraviolet spectrophotometer (Thermo Scientific NanoDrop 2000) using air as a blank, and the average value was taken by sampling three times. The results of the experiment are shown in table 4.

TABLE 4 light transmittance test results

Effect example 4

And (3) testing mechanical properties: after swelling the sample with physiological saline, cutting the sample into strips with the same shape of 40mm multiplied by 10mm, and adopting an electronic universal tester (for measuring the tensile strength and the elongation at break of the hydrogel material) according to the method described in GB528-82 under the condition of 10mm/min tensile speed at room temperature.

TABLE 5 mechanical Property test results

Finally, it should be noted that: the above embodiments are only used to illustrate the technical solution of the present invention, and not to limit the same; while the invention has been described in detail and with reference to the foregoing embodiments, it will be understood by those skilled in the art that: the technical solutions described in the foregoing embodiments may still be modified, or some or all of the technical features may be equivalently replaced; and the modifications or the substitutions do not make the essence of the corresponding technical solutions depart from the scope of the technical solutions of the embodiments of the present invention.

Claims

1. A hydrogel, wherein the hydrogel comprises the following raw materials: synthesizing monomers, a solubilizer, a cross-linking agent, an initiator, a catalyst and water; the synthetic monomers comprise HEMA and/or derivatives of HEMA; the dosage of each raw material is as follows according to the mass ratio of the raw materials to water:

synthesizing monomers: water is (0.5-20): 1;

solubilizer: water is (0.1-10): 1;

a crosslinking agent: water is (0.001-0.5): 1;

initiator: water is (0.05-2): 1;

catalyst: water is (0.05-2): 1.

2. the hydrogel of claim 1, wherein the derivative of HEMA comprises a HEMA functionalized derivative;

preferably, the functional group comprises-CH₃-CHO, -COOH and-NH₂At least one of;

preferably, the synthetic monomer has the formula (ii):

preferably, the synthetic monomer has a structural formula shown in (iii):

preferably, the synthetic monomer has the formula (iv):

preferably, the structural formula of said synthetic monomer is shown in (v):

3. the hydrogel of claim 1, wherein the cross-linking agent comprises a cross-linking agent comprising allyl reactive units;

preferably, the crosslinking agent containing allyl reactive units comprises at least one of polyethylene glycol diacrylate, ethylene glycol dimethacrylate, and triallyl isocyanurate; preferably comprising ethylene glycol dimethacrylate.

4. The hydrogel of claim 1, wherein the initiator comprises a thermal initiator or a photoinitiator;

preferably, the thermal initiator comprises an azo-type initiator or a peroxide-type initiator;

preferably, the azo-based initiator includes azobisisobutyronitrile;

preferably, the peroxide initiator comprises at least one of benzoyl peroxide, benzoyl tert-butyl peroxide and methyl ethyl ketone peroxide;

preferably, the or peroxide-based initiator comprises a persulfate; the persulfate preferably comprises ammonium persulfate and/or potassium persulfate;

preferably, the photoinitiator comprises at least one of 2-hydroxy-2-methyl propiophenone, ethyl 2,4, 6-trimethylbenzoylphosphonate and ethyl 2,4, 6-trimethylbenzoylphosphonate.

5. The hydrogel of claim 1, wherein the catalyst comprises a fatty amine catalyst;

preferably, the aliphatic amine catalyst comprises N, N' -tetramethylethylenediamine.

6. The hydrogel of claim 1, wherein the solubilizing agent comprises a polyol;

preferably, the polyol comprises glycerol.

7. The hydrogel according to any one of claims 1 to 6, wherein the amount of each raw material is as follows in terms of the mass ratio of each raw material to water:

synthesizing monomers: water is (5-20): 1;

solubilizer: water is (1-5): 1;

a crosslinking agent: water is (0.01-0.1): 1;

initiator: water is (0.1-1): 1;

catalyst: water is (0.1-1): 1;

preferably, the amount of each raw material is as follows in terms of the mass ratio of each raw material to water:

synthesizing monomers: water is 50: 3;

solubilizer: the ratio of water is 10: 3;

a crosslinking agent: the ratio of water is 1: 15;

initiator: the ratio of water is 2: 3;

catalyst: the ratio of water is 2: 3;

preferably, the synthetic monomer is HEMA; the solubilizer is glycerol; the cross-linking agent is ethylene glycol dimethacrylate; the initiator is ammonium persulfate; the catalyst is N, N, N ', N' -tetramethyl ethylenediamine.

8. The method for producing a hydrous gel as claimed in any one of claims 1 to 7, which comprises mixing a synthetic monomer, a solubilizer, a crosslinking agent, an initiator, a catalyst and water in a prescribed amount to react to obtain said hydrous gel;

preferably, the reaction is carried out at the temperature of 20-100 ℃, preferably 50-60 ℃, and more preferably 60 ℃;

preferably, the reaction time is 12-48 h, preferably 24 h;

preferably, synthetic monomers, a solubilizer, a cross-linking agent, an initiator, a catalyst and water are mixed according to the formula amount, then placed in a mold and reacted;

preferably, the preparation method further comprises removing unreacted materials in the hydrogel;

preferably, the hydrogel is soaked with ethanol and/or water to remove unreacted materials in the hydrogel;

preferably, an ethanol solution with the mass concentration of 25-35% of ethanol is used for soaking the hydrogel;

preferably, the mass concentration of the ethanol solution is 30%;

preferably, the soaking time is 2-5 days, preferably 3 days;

preferably, the hydrogel from which unreacted materials are removed is dried to obtain a hydrogel in a dry state;

preferably, the drying comprises vacuum drying;

preferably, the vacuum drying is carried out for 12-36 h, and preferably for 24 h.

9. A biofilm immobilization device prepared mainly from the hydrogel according to any one of claims 1 to 7 or mainly from the preparation method according to claim 8;

preferably, the contact surface of the biomembrane fixing device and the surface of the eyeball is in a ring shape with a radian, and the radian is matched with the radian of the surface of the eyeball.

10. Use of the hydrogel of any one of claims 1 to 7 or the method of making the hydrogel of claim 8 for the manufacture of a medical product.