CN106188411A - A kind of PEG type polythiourethane acrylic acid compound hydrogel material and its preparation method and application - Google Patents

Abstract

The invention belongs to the field of polymer materials, and in particular relates to a PEG-type polythiourethane-acrylic acid composite hydrogel material and its preparation method and application. The method comprises the following steps: S1. Using DMF as a solvent, polyethylene glycol dimercaptoacetate reacts with diisocyanate monomers to generate polythiourethane, then adds HEMA, and reacts to obtain PEG-type polythiourethane terminated by double bonds Ester; S2. Take the PEG-type polythiourethane terminated by the above-mentioned double bond and acrylic acid monomer and dissolve it in DMF, and ultrasonically treat the mixed solution, add photoinitiator and crosslinking agent to the mixed solution, and ultrasonically make it transparent S3. Pour the above precursor solution on a polytetrafluoroethylene plate and cover another plate, and use ultraviolet light to initiate polymerization to obtain a PEG-type polythiourethane-acrylic acid composite hydrogel material. The composite hydrogel material provided by the invention has a high equilibrium water content and a high refractive index, and has potential applications as a lens body material of a soft contact lens or an implant material of an artificial cornea.

Description

A kind of PEG type polythiourethane-acrylic acid composite hydrogel material and its preparation method and application

technical field

The invention belongs to the field of macromolecular materials, and in particular relates to a PEG-type polythiourethane-acrylic acid composite hydrogel material and its preparation method and application.

Background technique

Ophthalmic diseases are major diseases in medicine. At least dozens of ophthalmic diseases have been known so far. The most common ones include cataract, glaucoma, myopia, hyperopia, presbyopia, astigmatism, etc. Among various ophthalmic diseases, the most common Is myopia, the highest risk is cataract. In the past three decades, with the development and application of various new biomedical materials and new medical laser equipment, the ophthalmic medical device market has developed rapidly, such as corneal contact lenses, intraocular lenses, artificial corneas, and new protective glasses. Elastomers, etc.

Hydrogel is a kind of polymer with hydrophilic groups, which can absorb a large amount of water but can continue to maintain its original structure and insoluble three-dimensional network structure in water. Hydrogel is similar to living tissue materials, and its surface adhesion to proteins and cells is very weak. When in contact with blood, body fluids and human tissues, it shows good biocompatibility. It does not affect the metabolic process of living organisms. The metabolites can be discharged through the hydrogel, which has excellent biocompatibility and is widely used in biomedical materials. Polyurethane (PU) has good biocompatibility and excellent physical and mechanical properties, has good physiological acceptability to the human body, and can maintain the stability of long-term human implantation. By changing the composition of soft and hard segments in the molecular chain, it can Change the physical and chemical properties of polyurethane. The PU hydrogel prepared from PU polymer combines the advantages of both hydrogel and PU, which has aroused great research interest and has been well applied in the field of biomedicine.

Both the artificial cornea and the contact lens have certain requirements on the refractive index of the material. There are many ways to increase the refractive index of the material. One of the methods is to introduce a high molar refractive index and a small molecular volume into the polymer. Sulfur, halogen elements (except fluorine), aromatic rings, phosphorus atoms, heavy metal ions, condensed rings, etc. One of the most important reasons for the low refractive index of hydrogels with high water content is due to the low refractive index of water (1.33). If the free water in the hydrogel can be fixed by a certain force, it will inevitably further improve the water content. The refractive index of the gel.

Therefore, the present invention provides a PEG-type polythiourethane-acrylic acid composite hydrogel material with high refractive index and high water content. The present invention utilizes different isocyanic acid monomers to verify that the aromatic structure and aliphatic structure affect the refraction of the material. The influence of the ratio and the equilibrium water content, at the same time, using PEG with different molecular weights, a series of hydrogels with different molecular chain lengths were obtained, and the influence of the hydrogen bond strength on the refractive index and the equilibrium water content of the polymer was studied. The prepared PEG polythiourethane-acrylic acid composite hydrogel material has a higher refractive index than the human cornea, and its water content is similar to that of the human cornea.

Contents of the invention

Aiming at the deficiencies in the prior art, the technical problem to be solved by the present invention is to provide a PEG type polythiourethane-acrylic acid composite hydrogel material and its preparation method and application, the PEG type polythiourethane-acrylic acid composite hydrogel material Gel materials have both a high refractive index and a high water content.

The technical solution of the present invention to solve the above-mentioned technical problems is as follows: a PEG type polythiourethane-acrylic acid composite hydrogel material and its preparation method, is characterized in that, comprises the following steps:

S1. Using DMF as a solvent, polyvinyl dimercaptoacetate monomers react with diisocyanate monomers to generate PEG-type polythiourethane, and then add end-capping agent HEMA to obtain double-bond-terminated PEG-type polythiourethane after the reaction ester;

S2. Take an appropriate amount of double bond-terminated PEG-type polythiourethane and acrylic acid monomers prepared by S1 and dissolve them in an appropriate amount of DMF, and first ultrasonically treat the mixed solution, and add an appropriate amount of photoinitiator and crosslinking agent to the mixed solution , sonicate again to make it a transparent precursor solution;

S3. Pour the precursor solution in S2 on a polytetrafluoroethylene plate and press another polytetrafluoroethylene plate on it, and use ultraviolet light to irradiate the precursor solution through the polytetrafluoroethylene plate , initiate free radical polymerization to make it gel, and obtain PEG-type polythiourethane-acrylic acid composite hydrogel material.

On the basis of the above technical solutions, the present invention may also have the following further specific options or optimal options.

Preferably, the polyvinyl alcohol dimercaptoacetic acid monomer in step S1 is PEG200 dimercaptoacetic acid, PEG400 dimercaptoacetic acid, PEG600 dimercaptoacetic acid, PEG800 dimercaptoacetic acid, PEG1000 dimercaptoacetic acid and PEG1500 dimercaptoacetic acid any of the esters.

The chemical structure of the above-mentioned polyvinyl dimercaptoacetate is similar to ethylene glycol dimercaptoacetate, and it can be prepared by the following method: adding thioglycolic acid, polyethylene glycol, toluenesulfonic acid and DTT to the three ports of the oil-water separator In the flask, add toluene as a water-carrying agent, raise the temperature to 125-130°C under nitrogen protection, and react for 8-10h. After the reaction is completed, extract, separate, wash, remove water, rotary evaporate, and vacuum dry to obtain dimercaptoacetic acid polymer Vinyl alcohol ester, wherein the molar ratio of thioglycolic acid to polyethylene glycol is 2.05-2.15:1 (excessive amount of thioglycolic acid ensures capping of mercapto groups), and the molar ratio of toluenesulfonic acid to polyethylene glycol is 1-1.5: 100, the molar ratio of DTT to polyethylene glycol is 4.1-5.5:100, and the dosage ratio of water-carrying agent toluene to polyethylene glycol is 50-200mL:10-20g. Polyethylene glycol is PEG200, PEG400, PEG600, PEG800, PEG1000 or PEG1500, and the products generated by the reaction are correspondingly PEG200 dimercaptoacetic acid, PEG400 dimercaptoacetic acid, PEG600 dimercaptoacetic acid, PEG800 dimercaptoacetic acid, PEG1000 Thioglycolate and PEG1500 Dithioglycolate.

Preferably, the diisocyanate monomer in step S1 is any one of MDI, HDI, TDI, XDI and IPDI.

Specifically, the molar ratio of the diisocyanate monomer, polyvinyl dimercaptoacetate monomer and HEMA in step S1 is (2.5-4): 2: (1-4), and the quality of the DMF solvent in step S1 is The total mass of the polyvinyl alcohol dimercaptoacetate monomer, diisocyanate monomer and HEMA is 2.3-19 times.

Specifically, in the preparation process of the double-bond-terminated PEG-type polythiourethane in step S1, first calculate the amount of each substance in proportion, and mix the calculated amount of polyvinyl alcohol dimercaptoacetate monomer with half of the calculated amount of DMF solvent Put into the reaction vessel, mix the calculated amount of diisocyanate monomer with half of the calculated amount of DMF solvent and add it dropwise into the reaction vessel, raise the temperature to 30-80°C under the protection of argon, stir and carry out polymerization reaction to obtain PEG-type polythiourethane, after the reaction is completed, add the calculated amount of HEMA, raise the temperature to 30-80°C under the protection of argon, stir the reaction for 2-7 hours to seal the double bond, and dialysis the dialysis bag to remove unreacted small molecular monomers. After centrifugation and drying, the double bond-terminated PEG type polythiourethane is obtained.

Specifically, in step S2, the mass ratio of acrylic acid to double-bond-terminated PEG-type polythiourethane is 0.54-2.33, and the quality of DMF in step S2 is the total mass of the acrylic acid and double-bond-terminated PEG-type polythiourethane 1.5-4 times.

Specifically, the quality of the photoinitiator and crosslinking agent in step S2 is 0.85-1.25% of the total mass of the acrylic acid and double bond-terminated PEG type polythiourethane, and the photoinitiator is Darocur 1173, so The cross-linking agent is TEGDMA.

Specifically, the thickness of the liquid film of the precursor solution formed between the two polytetrafluoroethylene plates in step S3 is 20-200 μm.

The present invention also claims a PEG type polythiourethane-acrylic acid composite hydrogel material, which is prepared by the above method.

The present invention also claims to protect the application of the above-mentioned PEG type polythiourethane-acrylic acid composite hydrogel material as a lens body material of a soft contact lens or an implant material of an artificial cornea.

Compared with prior art, the beneficial effect of the present invention is:

1. The refractive index of the composite hydrogel material prepared by the preparation method of the present invention is higher than that of the human cornea, the equilibrium water content is similar to that of the human cornea, and has good biocompatibility. And contact lenses have a good application prospect;

2. The composite hydrogel material prepared by the preparation method of the present invention is clear and transparent, and the measured refractive index is as high as 1.558 in the dry state and 1.467 in the equilibrium water state, and the prepared hydrogel has the highest equilibrium water content It can reach 85%, which is a pure polymer hydrogel system, and its higher refractive index is a relatively big improvement compared with the prior art;

3. The composite hydrogel material provided by the present invention uses hydrogen bonds to fix the free water in the hydrogel, thereby effectively improving the refractive index of the material;

4. The present invention uses a series of PEG-type polythiourethanes as raw materials for preparing composite hydrogel materials. As the molecular weight of PEG increases, the hydrogen bonding of the composite hydrogel materials that are finally obtained also changes. Adjust the refractive index and water content;

5. The PEG-type polythiourethane designed by the present invention can be used to determine the refractive index and water content of the hydrogel through isocyanic acid with different aromatic rings and aliphatic structures and by changing the composition of soft and hard segments in the molecular chain. regulation;

6. The raw materials used to prepare the hydrogel material of the present invention have wide sources and are cheap, which is beneficial to reduce costs.

Description of drawings

Fig. 1 is a synthetic route diagram of a PEG type polythiourethane-acrylic acid composite hydrogel material provided by the present invention with double bond-terminated raw materials.

detailed description

The principles and features of the present invention are described below in conjunction with the accompanying drawings, and the examples given are only used to explain the present invention, and are not intended to limit the scope of the present invention.

The methods adopted in the following examples of the present invention are conventional methods unless otherwise specified, and the medicines used are all commercially available products unless otherwise specified. In the following examples, the synthetic route for preparing PEG-type polythiourethane-acrylic acid composite hydrogel material double-bond-terminated PEG-type polythiourethane is shown in FIG. 1 .

Example 1

A preparation method of PEG type polythiourethane-acrylic acid composite hydrogel material, comprising the steps:

S1. According to MDI, PEG200 dimercaptoacetic acid ester and HEMA molar ratio 3:2:2, the total mass of the three is 1g and the solid content after the three are dissolved in DMF solvent is 12.8% (DMF solvent is 6.8 times the total mass of the three solutes ), calculate the consumption of each raw material and solvent, add the three-necked flask with the calculated amount of dimercaptoacetic acid PEG200 ester and 3.4g DMF, the calculated amount of MDI and the 3.4gDMF are added dropwise, under argon, stirring and temperature React for 5 hours at 30°C. After 5 hours of reaction, add the calculated amount of HEMA, and react for 2 hours under argon gas, stirring, and temperature at 80°C to ensure that the double bonds are terminated. Use a dialysis bag with a molecular weight of 500 for 5 days to remove unresolved impurities. For the small molecular monomers to be reacted, a 1:1 ethanol aqueous solution was used for the first two days, followed by pure water, and the water was changed every 10 hours. Finally, it was centrifuged and dried in a vacuum oven at 50°C to obtain a white powdery double bond sealant. PEG-type polythiourethane at the end;

S2. Take 0.5g of the double-bond-terminated PEG-type polythiourethane prepared in step S1 and 0.5g of acrylic monomer dissolved in 1.5g of DMF, and first ultrasonic treatment (40-100w, 20-40kHz) for 10-30min to obtain a mixed solution 10 mg of photoinitiator Darocur 1173 and 10 mg of crosslinker TEGDMA were added to the mixed solution, and ultrasonic treatment (40-100w, 20-40kHz) was performed for 20-120s again to make it a transparent precursor solution;

S3. Pour the precursor solution in S2 onto a polytetrafluoroethylene plate and press another polytetrafluoroethylene plate on it, and use 300-400nm ultraviolet light to irradiate the polytetrafluoroethylene plate through the polytetrafluoroethylene plate. Precursor solution for 1-2 hours, initiate free radical polymerization to make it gel, and obtain PEG type polythiourethane-acrylic acid composite hydrogel material.

Example 2

A preparation method of PEG type polythiourethane-acrylic acid composite hydrogel material, comprising the steps:

S1. According to MDI, PEG400 dimercaptoacetic acid ester and HEMA molar ratio 2.5:2.0:1.0, the total mass of the three is 1g and the solid content after the three are dissolved in DMF solvent is 10% (DMF solvent is 9 times the total mass of the three solutes ), calculate the consumption of each raw material and solvent, add the three-necked flask with the calculated amount of dimercaptoacetic acid PEG400 ester and 4.5g DMF, the calculated amount of MDI and the 4.5g DMF are added dropwise, under argon, stirring and React for 3 hours at a temperature of 65°C. After 3 hours of reaction, add the calculated amount of HEMA, and react for 4 hours under argon gas, stirring, and a temperature of 60°C to ensure that the double bonds are terminated, and use a dialysis bag with a molecular weight of 500 for 5 days to remove For unreacted small molecular monomers, use 1:1 ethanol aqueous solution for the first two days, then change to pure water, change the water every 10 hours, and finally centrifuge and dry in a vacuum oven at 50°C to obtain a white powdery double bond End-blocked PEG type polythiourethane;

S2. Take 0.33g of the double bond-terminated PEG-type polythiourethane prepared in step S1 and 0.66g of acrylic monomer dissolved in 2.97g of DMF, and first ultrasonic treatment (40-100w, 20-40kHz) for 10-30min to get mixed solution, add 8.8mg of photoinitiator Darocur 1173 and 8.8mg of crosslinking agent TEGDMA to the mixed solution, and then ultrasonically treat (40-100w, 20-40kHz) for 20-120s to make it a transparent precursor solution;

S3. Pour the precursor solution in S2 onto a polytetrafluoroethylene plate and press another polytetrafluoroethylene plate on it, and use 300-400nm ultraviolet light to irradiate the polytetrafluoroethylene plate through the polytetrafluoroethylene plate. Precursor solution for 1-2 hours, initiate free radical polymerization to make it gel, and obtain PEG type polythiourethane-acrylic acid composite hydrogel material.

Example 3

A preparation method of PEG type polythiourethane-acrylic acid composite hydrogel material, comprising the steps:

S1. According to TDI, PEG200 dimercaptoacetic acid ester and HEMA molar ratio 3.5:2.0:3.0, the total mass of the three is 1g and the solid content after the three are dissolved in DMF solvent is 20% (DMF solvent is 4 times of the total mass of the three solutes ), calculate the consumption of each raw material and solvent, add the three-necked flask with the calculated amount of dimercaptoacetic acid PEG200 ester and 2g DMF, and add the TDI and 2gDMF of the calculated amount by adding dropwise, under argon, stirring and a temperature of 80 React for 2 hours at ℃. After 2 hours of reaction, add the calculated amount of HEMA, and react for 3 hours under argon, stirring and temperature at 50℃ to ensure that the double bonds are terminated. Use a dialysis bag with a molecular weight of 500 for 5 days to remove unreacted For small molecular monomers, 1:1 ethanol aqueous solution was used for the first two days, followed by pure water, and the water was changed every 10 hours. Finally, it was centrifuged and dried in a vacuum oven at 50°C to obtain white powdery double bond-terminated PEG. Type polythiourethane;

S2. Take 0.4g of the double-bond-terminated PEG-type polythiourethane prepared in step S1 and 0.6g of acrylic monomer dissolved in 4g of DMF, and first ultrasonic treatment (40-100w, 20-40kHz) for 10-30min to obtain a mixed solution 12.5mg of photoinitiator Darocur 1173 and 12.5mg of crosslinker TEGDMA were added to the mixed solution, and ultrasonic treatment (40-100w, 20-40kHz) was performed for 20-120s again to make it a transparent precursor solution;

S3. Pour the precursor solution in S2 onto a polytetrafluoroethylene plate and press another polytetrafluoroethylene plate on it, and use 250-380nm ultraviolet light to irradiate the polytetrafluoroethylene plate through the polytetrafluoroethylene plate. Precursor solution for 1-2 hours, initiate free radical polymerization to make it gel, and obtain PEG type polythiourethane-acrylic acid composite hydrogel material.

Example 4

A preparation method of PEG type polythiourethane-acrylic acid composite hydrogel material, comprising the steps:

S1. According to TDI, PEG400 dimercaptoacetic acid ester and HEMA molar ratio 4.0:2.0:4.0, the total mass of the three is 1g and the solid content after the three are dissolved in DMF solvent is 12.8% (DMF solvent is 6.8 times of the total mass of the three solutes ), calculate the consumption of each raw material and solvent, add the three-necked flask with the calculated amount of dimercaptoacetic acid PEG400 ester and 3.4g DMF, the TDI and the 3.4g DMF of the calculated amount are added dropwise, under argon, stirring and React for 2 hours at a temperature of 80°C. After 2 hours of reaction, add the calculated amount of HEMA, and react for 7 hours under argon gas, stirring, and a temperature of 30°C to ensure that the double bonds are terminated. Use a dialysis bag with a molecular weight of 500 for 5 days to remove For unreacted small molecular monomers, use 1:1 ethanol aqueous solution for the first two days, then change to pure water, change the water every 10 hours, and finally centrifuge and dry in a vacuum oven at 50°C to obtain a white powdery double bond End-blocked PEG type polythiourethane;

S2. Take 0.29g of the double-bond-terminated PEG-type polythiourethane prepared in step S1, and dissolve 0.71g of acrylic acid monomer in 3.5g of DMF, and perform the first ultrasonic treatment (40-100w, 20-40kHz) for 10-30min to obtain a mixed solution , add 9.4mg of photoinitiator Darocur 1173 and 11.2mg of crosslinking agent TEGDMA to the mixed solution, and ultrasonicate again (40-100w, 20-40kHz) for 20-120s to make it a transparent precursor solution;

S3. Pour the precursor solution in S2 onto a polytetrafluoroethylene plate and press another polytetrafluoroethylene plate on it, and use 300-400nm ultraviolet light to irradiate the polytetrafluoroethylene plate through the polytetrafluoroethylene plate. Precursor solution for 1-2 hours, initiate free radical polymerization to make it gel, and obtain PEG type polythiourethane-acrylic acid composite hydrogel material.

Example 5

A preparation method of PEG type polythiourethane-acrylic acid composite hydrogel material, comprising the steps:

S1. According to IPDI, PEG200 dimercaptoacetic acid ester and HEMA molar ratio 3.5:2:3.0, the total mass of the three is 1g and the solid content after the three are dissolved in DMF solvent is 12.8% (DMF solvent is 6.8 times the total mass of the three solutes ), calculate the consumption of each raw material and solvent, add the three-necked flask with the calculated amount of dimercaptoacetic acid PEG200 ester and 3.4g DMF, the calculated amount of IPDI and the 3.4g DMF adopt the mode of adding dropwise, under argon, stirring and React for 4 hours at a temperature of 50°C. After 4 hours of reaction, add the calculated amount of HEMA, and react for 2 hours under argon gas, stirring, and a temperature of 80°C to ensure that the double bonds are terminated. Use a dialysis bag with a molecular weight of 500 for 5 days to remove For unreacted small molecular monomers, use 1:1 ethanol aqueous solution for the first two days, then change to pure water, change the water every 10 hours, and finally centrifuge and dry in a vacuum oven at 50°C to obtain a white powdery double bond End-blocked PEG type polythiourethane;

S2. Take 0.5g of the double-bond-terminated PEG-type polythiourethane prepared in step S1 and 0.5g of acrylic monomer dissolved in 1.4g of DMF, and first ultrasonic treatment (40-100w, 20-40kHz) for 10-30min to obtain a mixed solution , add 9.5mg of photoinitiator Darocur 1173 and 8.5mg of crosslinking agent TEGDMA to the mixed solution, and ultrasonicate again (40-100w, 20-40kHz) for 20-120s to make it a transparent precursor solution;

S3. Pour the precursor solution in S2 onto a polytetrafluoroethylene plate and press another polytetrafluoroethylene plate on it, and use 300-400nm ultraviolet light to irradiate the polytetrafluoroethylene plate through the polytetrafluoroethylene plate. Precursor solution for 1-2 hours, initiate free radical polymerization to make it gel, and obtain PEG type polythiourethane-acrylic acid composite hydrogel material.

Example 6

A preparation method of PEG type polythiourethane-acrylic acid composite hydrogel material, comprising the steps:

S1. According to IPDI, PEG600 dimercaptoacetic acid ester and HEMA molar ratio 2.5:2:1, the total mass of the three is 1g and the solid content after the three are dissolved in DMF solvent is 12.8% (DMF solvent is 2.3 times the total mass of the three solutes ), calculate the consumption of each raw material and solvent, add the three-necked flask with the calculated amount of dimercaptoacetic acid PEG600 ester and 1.15g DMF, the IPDI of the calculated amount and the 1.15g DMF adopt the mode of adding dropwise, under argon, stirring and React for 2 hours at a temperature of 75°C. After 2 hours of reaction, add the calculated amount of HEMA, and react for 2 hours under argon gas, stirring, and a temperature of 75°C to ensure that the double bonds are terminated. Use a dialysis bag with a molecular weight of 500 for 5 days to remove For unreacted small molecular monomers, use 1:1 ethanol aqueous solution for the first two days, then change to pure water, change the water every 10 hours, and finally centrifuge and dry in a vacuum oven at 50°C to obtain a white powdery double bond End-blocked PEG type polythiourethane;

S2. Take 0.5g of the double-bond-terminated PEG-type polythiourethane prepared in step S1 and 0.5g of acrylic monomer dissolved in 2.5g of DMF, and first ultrasonic treatment (40-100w, 20-40kHz) for 10-30min to obtain a mixed solution 10 mg of photoinitiator Darocur 1173 and 10 mg of crosslinker TEGDMA were added to the mixed solution, and ultrasonic treatment (40-100w, 20-40kHz) was performed for 20-120s again to make it a transparent precursor solution;

S3. Pour the precursor solution in S2 onto a polytetrafluoroethylene plate and press another polytetrafluoroethylene plate on it, and use 300-400nm ultraviolet light to irradiate the polytetrafluoroethylene plate through the polytetrafluoroethylene plate. Precursor solution for 1-2 hours, initiate free radical polymerization to make it gel, and obtain PEG type polythiourethane-acrylic acid composite hydrogel material.

Example 7

A preparation method of PEG type polythiourethane-acrylic acid composite hydrogel material, comprising the steps:

S1. According to HDI, PEG800 dimercaptoacetic acid ester and HEMA molar ratio 2.5:2:1, the total mass of the three is 1g and the solid content after the three are dissolved in DMF solvent is 12.8% (DMF solvent is 2.3 times the total mass of the three solutes ) requirements, calculate the consumption of each raw material and solvent, add the three-necked flask of the calculated amount of dimercaptoacetic acid PEG800 ester and 1.15g DMF, the calculated amount of HDI and the 1.15g DMF are added dropwise, under argon, stirring and React for 2 hours at a temperature of 80°C. After 2 hours of reaction, add the calculated amount of HEMA, and react for 2 hours under argon gas, stirring, and a temperature of 80°C to ensure that the double bonds are terminated. Use a dialysis bag with a molecular weight of 500 for 5 days to remove For unreacted small molecular monomers, use 1:1 ethanol aqueous solution for the first two days, then change to pure water, change the water every 10 hours, and finally centrifuge and dry in a vacuum oven at 50°C to obtain a white powdery double bond End-blocked PEG type polythiourethane;

S2. Take 0.5g of the double-bond-terminated PEG-type polythiourethane prepared in step S1 and 0.5g of acrylic monomer dissolved in 2.5g of DMF, and first ultrasonic treatment (40-100w, 20-40kHz) for 10-30min to obtain a mixed solution 10 mg of photoinitiator Darocur 1173 and 10 mg of crosslinker TEGDMA were added to the mixed solution, and ultrasonic treatment (40-100w, 20-40kHz) was performed for 20-120s again to make it a transparent precursor solution;

S3. Pour the precursor solution in S2 onto a polytetrafluoroethylene plate and press another polytetrafluoroethylene plate on it, and use 300-400nm ultraviolet light to irradiate the polytetrafluoroethylene plate through the polytetrafluoroethylene plate. Precursor solution for 1-2 hours, initiate free radical polymerization to make it gel, and obtain PEG type polythiourethane-acrylic acid composite hydrogel material.

Example 8

A preparation method of PEG type polythiourethane-acrylic acid composite hydrogel material, comprising the steps:

S1. According to XDI, the molar ratio of PEG1000 dimercaptoacetic acid and HEMA is 3.0:2.0:2.0, the total mass of the three is 1g, and the solid content after the three are dissolved in DMF solvent is 12.8% (DMF solvent is 6.8 times the total mass of the three solutes ), calculate the consumption of each raw material and solvent, add the three-necked flask with the calculated amount of dimercaptoacetic acid PEG1000 ester and 3.4g DMF, the calculated amount of XDI and the 3.4g DMF are added dropwise, under argon, stirring and React for 2 hours at a temperature of 80°C. After 2 hours of reaction, add the calculated amount of HEMA, and react for 2 hours under argon gas, stirring, and a temperature of 80°C to ensure that the double bonds are terminated. Use a dialysis bag with a molecular weight of 500 for 5 days to remove For unreacted small molecular monomers, use 1:1 ethanol aqueous solution for the first two days, then change to pure water, change the water every 10 hours, and finally centrifuge and dry in a vacuum oven at 50°C to obtain a white powdery double bond End-blocked PEG type polythiourethane;

S2. Take 0.5g of the double-bond-terminated PEG-type polythiourethane prepared in step S1 and 0.5g of acrylic monomer dissolved in 2.5g of DMF, and first ultrasonic treatment (40-100w, 20-40kHz) for 10-30min to obtain a mixed solution 10 mg of photoinitiator Darocur 1173 and 10 mg of crosslinker TEGDMA were added to the mixed solution, and ultrasonic treatment (40-100w, 20-40kHz) was performed for 20-120s again to make it a transparent precursor solution;

S3. Pour the precursor solution in S2 onto a polytetrafluoroethylene plate and press another polytetrafluoroethylene plate on it, and use 300-400nm ultraviolet light to irradiate the polytetrafluoroethylene plate through the polytetrafluoroethylene plate. Precursor solution for 1-2 hours, initiate free radical polymerization to make it gel, and obtain PEG type polythiourethane-acrylic acid composite hydrogel material.

Example 9

A preparation method of PEG type polythiourethane-acrylic acid composite hydrogel material, comprising the steps:

S1. According to MDI, PEG1000 dimercaptoacetic acid ester and HEMA molar ratio 3.5:2.0:3.0, the total mass of the three is 1g and the solid content after the three are dissolved in DMF solvent is 12.2% (DMF solvent is 7.2 times the total mass of the three solutes ), calculate the consumption of each raw material and solvent, add the three-necked flask with the calculated amount of dimercaptoacetic acid PEG1000 ester and 3.6g DMF, the calculated amount of MDI and the 3.6g DMF are added dropwise, under argon, stirring and React for 2 hours at a temperature of 65°C. After 2 hours of reaction, add the calculated amount of HEMA, and react for 3 hours under argon gas, stirring, and a temperature of 65°C to ensure that the double bonds are terminated. Use a dialysis bag with a molecular weight of 500 for 5 days to remove For unreacted small molecular monomers, use 1:1 ethanol aqueous solution for the first two days, then change to pure water, change the water every 10 hours, and finally centrifuge and dry in a vacuum oven at 50°C to obtain a white powdery double bond End-blocked PEG type polythiourethane;

S2. Take 0.5g of the double-bond-terminated PEG-type polythiourethane prepared in step S1 and 0.5g of acrylic monomer dissolved in 3.3g of DMF, and first ultrasonic treatment (40-100w, 20-40kHz) for 10-30min to obtain a mixed solution 12 mg of photoinitiator Darocur 1173 and 12 mg of crosslinker TEGDMA were added to the mixed solution, and ultrasonic treatment (40-100w, 20-40kHz) was performed for 20-120s again to make it a transparent precursor solution;

S3. Pour the precursor solution in S2 onto a polytetrafluoroethylene plate and press another polytetrafluoroethylene plate on it, and use 300-400nm ultraviolet light to irradiate the polytetrafluoroethylene plate through the polytetrafluoroethylene plate. Precursor solution for 1-2 hours, initiate free radical polymerization to make it gel, and obtain PEG type polythiourethane-acrylic acid composite hydrogel material.

Example 10

A preparation method of PEG type polythiourethane-acrylic acid composite hydrogel material, comprising the steps:

S1. According to HDI, PEG1000 dimercaptoacetic acid ester and HEMA molar ratio 3.0:2.0:2.0, the total mass of the three is 1g and the solid content after the three are dissolved in DMF solvent is 40% (DMF solvent is 1.5 times the total mass of the three solutes ), calculate the consumption of each raw material and solvent, add the three-necked flask with the calculated amount of dimercaptoacetic acid PEG1000 ester and 0.75g DMF, and add the calculated amount of HDI and 0.75g DMF in a dropwise manner, under argon, stirring and React for 3 hours at a temperature of 55°C. After 2 hours of reaction, add the calculated amount of HEMA, and react for 3 hours under argon gas, stirring, and a temperature of 55°C to ensure that the double bonds are terminated. Use a dialysis bag with a molecular weight of 500 for 5 days to remove For unreacted small molecular monomers, use 1:1 ethanol aqueous solution for the first two days, then change to pure water, change the water every 10 hours, and finally centrifuge and dry in a vacuum oven at 50°C to obtain a white powdery double bond End-blocked PEG type polythiourethane;

S2. Take 0.29g of the double-bond-terminated PEG-type polythiourethane prepared in step S1, and dissolve 0.71g of acrylic acid monomer in 2.1g of DMF, and perform the first ultrasonic treatment (40-100w, 20-40kHz) for 10-30min to obtain a mixed solution , add 9 mg of photoinitiator Darocur 1173 and 9 mg of crosslinker TEGDMA to the mixed solution, and ultrasonicate again (40-100w, 20-40kHz) for 20-120s to make it a transparent precursor solution;

S3. Pour the precursor solution in S2 onto a polytetrafluoroethylene plate and press another polytetrafluoroethylene plate on it, and use 300-400nm ultraviolet light to irradiate the polytetrafluoroethylene plate through the polytetrafluoroethylene plate. Precursor solution for 1-2 hours, initiate free radical polymerization to make it gel, and obtain PEG type polythiourethane-acrylic acid composite hydrogel material.

Example 11

A preparation method of PEG type polythiourethane-acrylic acid composite hydrogel material, comprising the steps:

S1. According to MDI, PEG1500 dimercaptoacetic acid ester and HEMA molar ratio 3:2:2.5, the total mass of the three is 1g and the solid content after the three are dissolved in DMF solvent is 5.3% (DMF solvent is 17 times the total mass of the three solutes ), calculate the consumption of each raw material and solvent, add the three-necked flask with the calculated amount of dimercaptoacetic acid PEG1500 ester and 8.5g DMF, the calculated amount of MDI and the 8.5g DMF are added dropwise, under argon, stirring and React for 2 hours at a temperature of 75°C. After 2 hours of reaction, add the calculated amount of HEMA, and react for 2 hours under argon gas, stirring, and a temperature of 75°C to ensure that the double bonds are terminated. Use a dialysis bag with a molecular weight of 500 for 5 days to remove For unreacted small molecular monomers, use 1:1 ethanol aqueous solution for the first two days, then change to pure water, change the water every 10 hours, and finally centrifuge and dry in a vacuum oven at 50°C to obtain a white powdery double bond End-blocked PEG type polythiourethane;

S2. Take 0.29g of the double-bond-terminated PEG-type polythiourethane prepared in step S1 and 0.71g of acrylic monomer dissolved in 1.9g of DMF, and first ultrasonic treatment (40-100w, 20-40kHz) for 10-30min to obtain a mixed solution , add 9.1 mg of photoinitiator Darocur 1173 and 9.1 mg of crosslinker TEGDMA to the mixed solution, and ultrasonicate again (40-100w, 20-40kHz) for 20-120s to make it a transparent precursor solution;

S3. Pour the precursor solution in S2 onto a polytetrafluoroethylene plate and press another polytetrafluoroethylene plate on it, and use 300-400nm ultraviolet light to irradiate the polytetrafluoroethylene plate through the polytetrafluoroethylene plate. Precursor solution for 1-2 hours, initiate free radical polymerization to make it gel, and obtain PEG type polythiourethane-acrylic acid composite hydrogel material.

Example 12

A preparation method of PEG type polythiourethane-acrylic acid composite hydrogel material, comprising the steps:

S1. According to IPDI, PEG1500 dimercaptoacetic acid ester and HEMA molar ratio 3.5:2:2.5, the total mass of the three is 1g and the solid content after the three are dissolved in DMF solvent is 12.8% (DMF solvent is 6.8 times the total mass of the three solutes ), calculate the consumption of each raw material and solvent, add the three-necked flask with the calculated amount of dimercaptoacetic acid PEG1500 ester and 3.4g DMF, the calculated amount of IPDI and the 3.4g DMF adopt the mode of adding dropwise, under argon, stirring and React for 2 hours at a temperature of 60°C. After 2 hours of reaction, add the calculated amount of HEMA, and react for 2 hours under argon, stirring, and a temperature of 60°C to ensure that the double bonds are terminated. Use a dialysis bag with a molecular weight of 500 for 5 days to remove For unreacted small molecular monomers, use 1:1 ethanol aqueous solution for the first two days, then change to pure water, change the water every 10 hours, and finally centrifuge and dry in a vacuum oven at 50°C to obtain a white powdery double bond End-blocked PEG type polythiourethane;

S2. Take 0.29g of the double-bond-terminated PEG-type polythiourethane prepared in step S1, and dissolve 0.71g of acrylic acid monomer in 3.2g of DMF, and perform the first ultrasonic treatment (40-100w, 20-40kHz) for 10-30min to obtain a mixed solution 12 mg of photoinitiator Darocur 1173 and 12 mg of crosslinker TEGDMA were added to the mixed solution, and ultrasonic treatment (40-100w, 20-40kHz) was performed for 20-120s again to make it a transparent precursor solution;

S3. Pour the precursor solution in S2 onto a polytetrafluoroethylene plate and press another polytetrafluoroethylene plate on it, and use 300-400nm ultraviolet light to irradiate the polytetrafluoroethylene plate through the polytetrafluoroethylene plate. Precursor solution for 1-2 hours, initiate free radical polymerization to make it gel, and obtain PEG type polythiourethane-acrylic acid composite hydrogel material.

performance testing

The equilibrium water content, the refractive index in the equilibrium water-containing state, and the refractive index in the dry state of the PEG-type polythiourethane-acrylic acid composite hydrogel materials prepared in Examples 1 to 12 were tested. Put the PEG-type polythiourethane-acrylic acid composite hydrogel materials prepared in each embodiment into a large amount of water to wash, so that the unreacted soluble substances in the hydrogel are exchanged, and then soak them in deionized water for at least 3 days , to make it reach the equilibrium water-containing state and test its equilibrium water-containing state refractive index and moisture content (Nd _wet ), then dry it according to conventional methods and requirements, and test its dry state refractive index (Nd _dry ) after drying, each The sample of embodiment measures 4 times, gets average value again, and the corresponding result of measuring is shown in the following table:

As can be seen from the data in the table above, the equilibrium water content, dry refractive index, and wet refractive index of the PEG type polythiourethane-acrylic acid composite hydrogel material prepared by the present invention are all higher, and the content of acrylic acid in the hydrogel is controlled. The content can adjust the equilibrium water content and refractive index of the hydrogel, and the refractive index and water content of the hydrogel can also be adjusted by adding isocyanic acid with different aromatic rings and aliphatic structures and by changing the composition of the soft and hard segments in the molecular chain. Certain regulation, in addition, by controlling the molecular weight of PEG in PEG type polythiourethane also can suitably regulate and control the refractive index and the equilibrium water content of final composite hydrogel; Adjust to obtain a hydrogel material with a specific balance of water content and refractive index; the composite hydrogel material prepared by the present invention has great potential applications as soft contact lens materials and artificial corneal implant materials.

The above descriptions are only preferred embodiments of the present invention, and are not intended to limit the present invention. Any modifications, equivalent replacements, improvements, etc. made within the spirit and principles of the present invention shall be included in the protection of the present invention. within range.

Claims (10)

1. a preparation method of PEG type polythiourethane-acrylic acid composite hydrogel material, is characterized in that, comprises the steps: S1. Using DMF as a solvent, polyvinyl dimercaptoacetate monomers react with diisocyanate monomers to generate PEG-type polythiourethane, and then add end-capping agent HEMA to obtain double-bond-terminated PEG-type polythiourethane after the reaction ester; S2. Take the double-bond-terminated PEG-type polythiourethane and acrylic acid monomers prepared in S1 and dissolve them in DMF, and ultrasonically treat the mixed solution for the first time, add a photoinitiator and a cross-linking agent to the mixed solution, and ultrasonically again treatment to make it a transparent precursor solution; S3. Pour the precursor solution in S2 on a polytetrafluoroethylene plate and press another polytetrafluoroethylene plate on it, and use ultraviolet light to irradiate the precursor solution through the polytetrafluoroethylene plate , initiate free radical polymerization to make it gel, and obtain PEG-type polythiourethane-acrylic acid composite hydrogel material. 2. the preparation method of a kind of PEG type polythiourethane-acrylic acid composite hydrogel material according to claim 1, is characterized in that, the dimercaptoacetic acid polyvinyl alcohol ester monomer in step S1 is dimercaptoacetic acid PEG200 Any one of esters, PEG400 dimercaptoacetate, PEG600 dimercaptoacetate, PEG800 dimercaptoacetate, PEG1000 dimercaptoacetate and PEG1500 dimercaptoacetate. 3. the preparation method of a kind of PEG type polythiourethane-acrylic acid composite hydrogel material according to claim 1, is characterized in that, the diisocyanate monomer in step S1 is MDI, HDI, TDI, XDI and Any of IPDI. 4. the preparation method of a kind of PEG type polythiourethane-acrylic acid composite hydrogel material according to claim 1, is characterized in that, the diisocyanate monomer in step S1, polyvinyl alcohol dimercaptoacetate monomer The mol ratio of solid and HEMA is (2.5-4): 2: (1-4), the quality of DMF solvent is described polyvinyl dimercaptoacetic acid ester monomer, diisocyanate monomer and HEMA total mass in step S1 2.3-19 times. 5. the preparation method of a kind of PEG type polythiourethane-acrylic acid composite hydrogel material according to claim 4, is characterized in that, in the preparation process of the PEG type polythiourethane of double bond termination in step S1, First, calculate the amount of each substance in proportion, add the calculated amount of polyvinyl alcohol dimercaptoacetate monomer and half of the calculated amount of DMF solvent into the reaction vessel, and add the calculated amount of diisocyanate monomer and half of the calculated amount of DMF solvent Mix and add dropwise into the reaction vessel, raise the temperature to 30-80°C under the protection of argon, and carry out the polymerization reaction with stirring to obtain PEG-type polythiourethane. After the reaction is completed, add the calculated amount of HEMA, and raise the temperature under the protection of argon. to 30-80°C, stirred and reacted for 2-7 hours to seal the double bond, dialyze the dialysis bag to remove unreacted small molecular monomers, centrifuge and dry to obtain the double bond-terminated PEG type polythiourethane. 6. according to the preparation method of a kind of PEG type polythiourethane-acrylic acid composite hydrogel material described in any one of claim 1 to 5, it is characterized in that, in step S2, the PEG type polysulfide of acrylic acid and double bond termination The mass ratio of urethane is 0.54-2.33, and the mass of DMF in step S2 is 1.5-4 times of the total mass of the acrylic acid and double bond-terminated PEG-type polythiourethane. 7. the preparation method of a kind of PEG type polythiourethane-acrylic acid composite hydrogel material according to claim 6, is characterized in that, the quality of photoinitiator and linking agent in step S2 is described acrylic acid 0.85-1.25% of the total mass of PEG-type polythiourethane blocked by double bonds, the photoinitiator is Darocur 1173, and the crosslinking agent is TEGDMA. 8. according to the preparation method of a kind of PEG type polythiourethane-acrylic acid composite hydrogel material described in any one of claim 1 to 5, it is characterized in that, form between two polytetrafluoroethylene plates in step S3 The liquid film thickness of the precursor solution is 20-200 μm. 9. A PEG type polythiourethane-acrylic acid composite hydrogel material, characterized in that it is prepared by the method according to any one of claims 1 to 8. 10. The application of PEG type polythiourethane-acrylic acid composite hydrogel material as claimed in claim 9, is characterized in that, it is used as the lens body material of soft contact lens or the implant material of artificial cornea.