Method for preparing silicon-containing prepolymer, silicon-containing prepolymer and silicon hydrogel film

Abstract

The invention relates to a method for preparing a silicon-containing prepolymer, the silicon-containing prepolymer and a silicon hydrogel film. The preparation method of the silicon-containing prepolymer comprises the following steps: mixing water, a cosolvent and a silicon-containing hydrophobic monomer according to a molar ratio to form a mixture; hydrochloric acid is added into the mixture, substitution and hydrolysis reactions are carried out to obtain substitution and hydrolysis products, the molar concentration of the hydrochloric acid is 0.001-0.005 times of the molar concentration of the silicon-containing hydrophobic monomer, and the pH of the mixture is smaller than or equal to 1; and adding a hydroxyl-containing hydrophilic compound into the substitution and hydrolysis product, and carrying out condensation reaction to obtain the silicon-containing prepolymer. In addition, the invention also relates to the silicon-containing prepolymer and the silicon hydrogel film prepared by the method.

Description

Technical Field

[0001] The present invention relates to a method for preparing a hydrophilic silicon-containing prepolymer, a hydrophilic silicon-containing prepolymer and a hydrophilic silicon hydrogel film, in particular, a method for preparing a hydrophilic silicon-containing prepolymer by hydrolysis-condensation reaction, and the hydrophilic silicon-containing prepolymer and the hydrophilic silicon hydrogel film prepared by the method, so as to be applied to materials for contact lenses. Background Art

[0002] When designing contact lenses, the choice of materials will directly affect the user's wearing experience, such as lens water content, oxygen permeability or mechanical properties. When the lens water content is too low, it is easy to cause protein deposition, bloodshot, dry eyes and other phenomena; low oxygen permeability will cause corneal swelling. Early soft contact lens materials used polyhydroxyethyl methacrylate

[0003] (PHEMA), but its oxygen permeability is low, which often causes corneal hypoxia in wearers. In order to solve the side effects caused by low oxygen permeability of contact lenses and meet the requirements of long-term wear, silicone hydrogel contact lenses have been developed in recent years to solve the problem of low oxygen permeability.

[0004] The sol-gel method is an important wet chemical technology that can synthesize organic-inorganic hybrids at relatively low temperatures. Silicone hydrogels prepared by the sol-gel method are widely used in the preparation of contact lenses. In the conventional sol-gel method, tetraalkylsiloxane (TAOS) obtained by the reaction of silicon tetrachloride and ethanol undergoes hydrolysis and condensation reactions under acid catalysis to produce silicon dioxide, which is a transparent glass material. In the conventional process of preparing silicone hydrogel by the sol-gel method, the material monomers commonly used are siloxane-based compounds, such as tetramethylsiloxane (TMOS), tetraethylsiloxane (TEOS), etc. Siloxane-based compounds form silica gel through hydrolysis and condensation reactions, and the reaction mechanism is as follows:

[0005] hydrolysis

[0006]

[0007] Alcohol condensation

[0008]

[0009] Water condensation

[0010]

[0011] Overall reaction

[0012]

[0013] In the reaction formulas 2-1 to 2-4, the siloxane group (Si-OR) undergoes hydrolysis to produce silanol (Si-OH). Once the hydrolysis reaction occurs, it is accompanied by a condensation reaction, including the alcohol condensation of formula 2-5 and the water condensation of formula 2-6, which respectively produce alcohol and water as side reactants. The polymerization reaction is mainly based on the condensation of the silanol group.

[0014] The use of the sol-gel method to produce organic / inorganic hybrid materials can combine the dual characteristics of the materials and help design new materials with different properties. In recent years, it has become a widely watched material preparation technology. Traditional silicone hydrogels are usually prepared by polymerization of siloxane monomers and hydrophilic monomers. The prepared silicone hydrogels have a siloxane structure that transfers oxygen and can effectively increase the oxygen permeability. However, the biggest problem with this traditional silicone hydrogel is that during the polymerization of siloxane monomers and hydrophilic monomers, since the silicon group in the siloxane monomer is hydrophobic, the hydrophilic monomers and siloxane monomers in the hydrogel are prone to phase separation, resulting in the opacity of the silicone hydrogel, which in turn affects its oxygen permeability; in addition, it will also cause the surface of the silicone hydrogel lens to exhibit hydrophobic properties, which is easy to accumulate sediment and cause eye discomfort. Therefore, how to synthesize hydrophilic silicon molecules suitable for silicone hydrogel contact lenses, and in order to increase the oxygen permeability of contact lenses and compatibility with hydrophilic monomers, solve the problems of phase separation, improve hydrophilicity and oxygen permeability, etc., are important bottlenecks that must be overcome in designing silicone hydrogel contact lens formulas.

[0015] In view of this, in order to overcome the problems of conventional silicone hydrogels, there is a need for methods and materials for preparing contact lens materials with high hydrophilicity, high oxygen permeability and good biocompatibility. Summary of the invention

[0016] The object of the present invention is to provide a method for preparing a silicon-containing prepolymer. In addition to being relatively simple in preparation, the method can also solve the problem of phase separation between hydrophilic monomers and siloxane monomers in hydrogels, thereby causing the opacity of silicone hydrogels, and improve the water content and oxygen permeability, as well as the biocompatibility, etc. of the silicone hydrogel prepared from the silicon-containing prepolymer.

[0017] According to the above concept, the present invention provides a method for preparing a silicon-containing prepolymer, comprising: mixing water, a co-solvent and a silicon-containing hydrophobic monomer in a molar ratio to form a mixture; adding hydrochloric acid to the mixture to carry out substitution and hydrolysis reactions to obtain a substitution and hydrolysis product, wherein the molar concentration of the hydrochloric acid is 0.001 to 0.005 times the molar concentration of the silicon-containing hydrophobic monomer, so that the pH of the mixture is ≤1; and adding a hydroxyl-containing hydrophilic compound to the substitution and hydrolysis product to carry out a condensation reaction to obtain the silicon-containing prepolymer.

[0018] According to one embodiment, in the method, the molar number of water is 1 to 20 times the molar number of the silicon-containing hydrophobic monomer; the molar number of the co-solvent is 1 to 20 times the molar number of the silicon-containing hydrophobic monomer; the molar number of the hydroxyl-containing hydrophilic compound is 1 to 3 times the molar number of the silicon-containing hydrophobic monomer; the reaction temperature of the substitution and hydrolysis reaction is 25°C to 40°C, and the reaction time of the substitution and hydrolysis reaction is 3 to 12 hours; the reaction temperature of the condensation reaction is 50°C to 80°C, and the reaction time of the condensation reaction is 3 to 12 hours; the co-solvent is one of methanol, ethanol, isopropanol, acetone and tetrahydrofuran (THF); the silicon-containing hydrophobic monomer is methacrylic acid; The invention relates to a method for preparing the hydrophilic silicon-containing compound comprising: acryloxypropyl tris(trimethylsiloxy)silane, (3-methacrylamidepropyl)bis(trimethylsiloxy)silane, bis(trimethylsiloxy)silylpropyl glyceryl methyl methacrylate, and acrylamidepropyl tris(trimethoxysiloxy)silane; and the hydroxyl-containing hydrophilic compound is one of hydroxyethyl methacrylate (HEMA), hydroxybutyl methacrylate, glyceryl monomethacrylate, bis(trimethylsiloxy)silylpropyl glyceryl methyl methacrylate), hydroxypropyl methacrylate, 4-hydroxybutyl acrylate, 2-hydroxybutyl acrylate, and polyethylene glycol (PEG); and the molar ratio of water, co-solvent, and silicon-containing hydrophobic monomer is 3:3:1.

[0019] According to one embodiment, the method further comprises: concentrating the silicon-containing prepolymer under reduced pressure at 60°C.

[0020] Based on the above concept, the present invention further provides a silicone hydrogel film, which is made from the silicon-containing prepolymer prepared by the above method.

[0021] Based on the above concept, the present invention further proposes a method for preparing a silicon-containing prepolymer, comprising: performing a substitution and hydrolysis reaction of water, a co-solvent and a silicon-containing hydrophobic monomer in an acidic environment containing hydrochloric acid to obtain a substitution and hydrolysis product, wherein the molar number of the hydrochloric acid is 0.001 to 0.005 times the molar number of the silicon-containing hydrophobic monomer; and performing a condensation reaction of a hydroxyl-containing hydrophilic compound and the substitution and hydrolysis product to obtain the silicon-containing prepolymer.

[0022] Based on the above concept, the present invention further provides a silicone hydrogel film, which is prepared from the silicon-containing prepolymer prepared by the above method.

[0023] In addition, according to the above concept, the present invention provides a substitution and hydrolysis product obtained by substitution and hydrolysis reaction of water, co-solvent and silicon-containing hydrophobic monomer, wherein: the substitution and hydrolysis reaction is carried out in an acidic environment containing hydrochloric acid; and the molar number of hydrochloric acid is 0.001 to 0.005 times the molar number of the silicon-containing hydrophobic monomer.

[0024] Based on the above concept, the present invention provides a method for preparing a substitution and hydrolysis product, comprising: providing water; providing a co-solvent; providing a silicon-containing hydrophobic monomer; and subjecting the water, the co-solvent and the silicon-containing hydrophobic monomer to a substitution and hydrolysis reaction in an acidic environment containing hydrochloric acid, wherein the molar number of the hydrochloric acid is 0.001 to 0.005 times the molar number of the silicon-containing hydrophobic monomer, to obtain the substitution and hydrolysis product. BRIEF DESCRIPTION OF THE DRAWINGS

[0025] The above objects and advantages of the present invention will become more apparent to those skilled in the art after referring to the following detailed description and the accompanying drawings.

[0026] Figure 1 : Shows the preparation method of the hydrophilic silicon-containing prepolymer of the present invention.

[0027] Figure 2 :Show the preparation method of the silicone hydrogel film of the present invention DETAILED DESCRIPTION

[0028] The present invention will be fully understood by the following embodiments, so that those with ordinary knowledge in the technical field can complete it; however, the implementation of the present invention is not limited to the following embodiments, and those with ordinary knowledge in the technical field can still deduce other embodiments based on the spirit of the disclosed embodiments, and these embodiments should all fall within the scope of the present invention.

[0029] Unless otherwise limited or indicated in specific examples, the following definitions apply to the terms used throughout the specification.

[0030] The terms “comprise” or “include” used herein mean that in addition to the described components, steps, and / or elements, the existence of one or more other components, steps, and / or elements is not excluded.

[0031] The terms "approximately" or "about" used herein mean having an approximate or allowable error range, and are used to avoid limiting the present invention to the exact or absolute values ​​disclosed. The terms "a" and "an" used herein mean that the grammatical object of the article is one or more than one.

[0032] The present invention uses a sol-gel method to produce a silicon-containing prepolymer by organic-inorganic hybridization. The silicon-containing hydrophobic monomer such as a siloxane polymer (for example, methacryloxypropyl tris(trimethylsiloxane)silane (TRIS)) and a hydroxyl-containing hydrophilic compound such as hydroxyethyl methacrylate (HEMA) monomer are mainly used to produce a silicone hydrogel prepolymer through a hydrolysis substitution reaction and a condensation reaction under acidic catalyst catalysis conditions; further, the obtained prepolymer can be mixed with other components and polymerized through a photopolymerization method or a thermal polymerization method to obtain a high oxygen permeability and functional silicone hydrogel film, which can be used as a soft contact lens material. Different from the conventional sol-gel method, the method for preparing a silicon-containing prepolymer proposed by the present invention has a reaction mechanism under hydrochloric acid solution catalysis conditions as follows:

[0033] Hydrolytic substitution reaction

[0034]

[0035] Condensation reaction

[0036]

[0037] Among them, the sol-gel method to produce silicone hydrogel prepolymer mainly includes hydrolysis substitution reaction and condensation reaction:

[0038] 1. In the substitution hydrolysis reaction, the oxygen atoms on the silicon-oxygen-silicon group (Si-O-Si) in the TRIS structure are replaced by hydrogen ions (H + ) is protonated (Formula 1); then, the chloride ion (Cl-) is easily attracted to the silicon atom, and the protonated silanol (Si-OH) will leave, so the chloride ion undergoes a nucleophilic substitution reaction and reverses to form a silyl chloride alkyl (≡Si-Cl) (Formula 2), which is S N 2. Reaction mechanism; the obtained silyl chloride reacts with water molecules to produce silanol (Si-OH), as shown in Formula 3; and 2. In the condensation reaction, the -OH group on the HEMA structure acts as a nucleophile to react with the silyl chloride. N 2, or a condensation reaction with silanol to produce a Si-OC structure, as shown in Formulas 4 and 5.

[0039] Silanol can also undergo condensation reaction with other generated silanols to produce Si-O-Si structure, as shown in Formula 6.

[0040] Therefore, through the sol-gel reaction, HEMA and TRIS can undergo a covalent bonding reaction to produce a silicon-containing prepolymer.

[0041] The silicon-containing prepolymer and the preparation method thereof of the present invention will be described below with specific embodiments.

[0042] Preparation of Silicon-Containing Prepolymer

[0043] In the method for preparing a hydrophilic silicon-containing prepolymer by a sol-gel method proposed in the present invention, a siloxane polymer, water and a hydroxyl-containing hydrophilic compound are used as materials. Since the solubility of the siloxane polymer in water is not large, a co-solvent is added in the present invention to make the two easy to mix so that the silicon-containing hydrophobic monomer and water will not separate when they are mixed. Alcohols, such as ethanol, are usually used as co-solvents.

[0044] In a first embodiment, a method for preparing a silicon-containing prepolymer is provided. Figure 1 , which shows the preparation method of the hydrophilic silicon-containing prepolymer of the present invention, the preparation method comprises the following steps

[0045] step:

[0046] Step 110: Mix 3 moles of water, 3 moles of ethanol, and 1 mole of TRIS at room temperature to obtain a mixture;

[0047] Step 120: Add 12M hydrochloric acid to the mixture to adjust the pH value of the mixture to ≤1.

[0048] The pH-adjusted mixture was subjected to substitution and hydrolysis reaction at 30° C. for 6 hours to obtain a substitution and hydrolysis product;

[0049] Step 130: adding 3 moles of HEMA monomer to the substituted and hydrolyzed product of step 130, and performing a condensation reaction at 60° C., wherein the solution is turbid. After a reaction time of about 5 hours, a clear product, i.e., the silicon-containing prepolymer of the present invention, can be obtained. Based on the clear product, it can be determined that HEMA and TRIS have successfully reacted to form a covalent bond; and Step 140: concentrating the clear product under reduced pressure at 60° C. to remove the solvent and low-boiling substances in the solution.

[0050] Thus, a transparent and clear silicon-containing prepolymer is obtained.

[0051] The silicon-containing prepolymer system prepared by the above method steps was characterized by Fourier transform infrared spectroscopy (ATR-FTIR) and nuclear magnetic resonance spectroscopy ( 13 C-NMR) for structural analysis.

[0052] According to the FTIR analysis spectrum of the silicon-containing prepolymer, it can be observed that the -1An absorption peak appears at , which is Si-OC bonding (see Ji XL, Jiang SC, Qiu XP, Dong DW, Yu DH, Jiang BZ. Structure and properties of hybrid poly (2-hydroxyethyl methacrylate) / SiO2 monoliths. Journal of Applied Polymer Science. 2003; 88: 3168-75). The appearance of this characteristic peak indicates that at a higher temperature, the HEMA monomer and the siloxane in the TRIS monomer produce a sol-gel reaction, and the C-OH group in the HEMA monomer may react with the Si-OH intermediate to form a Si-OC structure by removing water molecules, or the C-OH group on the HEMA structure plays a nucleophilic agent and reacts with the silyl chloride alkyl (≡Si-Cl) to form a Si-OC structure. N 2 reaction, producing Si-OC structure. Compared with HEMA monomer, silicon-containing prepolymer has a peak at 3500-3400 cm -1 There is no obvious hydroxyl (-OH) absorption peak in the range.

[0053] In addition to the above-mentioned analysis of the functional group structure of the silicon-containing prepolymer using FTIR, the structure of the silicon-containing prepolymer was also analyzed using nuclear magnetic resonance to determine whether the covalent bonding between the HEMA monomer and the TRIS monomer was indeed successful. 13 C-NMR spectrum shows that at higher temperatures, the C-OH group in the HEMA monomer may react with the Si-OH group or the silyl chloride group (≡Si-Cl) to produce a Si-OC structure. Compared with the other two monomers, the TRIS / HEMA prepolymer has a characteristic peak at 65ppm, which is inferred to be a Si-OC bond (see Costela A, García-Moreno I, Gómez C, GarcíO, Garrido L, Sastre R. Highly efficient and stable doped hybrid organic-inorganic materials for solid-state dye lasers. Chemical Physics Letters. 2004; 387: 496-501), so it can be known that HEMA and TRIS have successfully produced covalent bonds.

[0054] Although the exact structural formula of the silicon-containing prepolymer cannot be drawn from the results of NMR and IR, it can be confirmed that the reactants have indeed undergone hydrolysis-condensation polymerization.

[0055] In a second embodiment, a method for preparing a silicon-containing prepolymer is provided. The method is to prepare the silicon-containing prepolymer of the present invention by the same steps as those described in the first embodiment, except that the components of each reaction, the amount of hydrochloric acid used, and the reaction time can be changed differently. TRIS is a structure containing three silicon-oxygen-silicon groups. In the hydrolysis reaction of TRIS and water, the molar number of water can be at least about one time, preferably three times, the molar number of TRIS, so that TRIS can be fully hydrolyzed. Generally, the molar number of water can be about 1 to 20 times the molar number of TRIS to achieve the effect of hydrolyzing TRIS. As for the molar number of ethanol as a co-solvent, it can be adjusted between about 1 and 20 times the molar number of TRIS to make water and TRIS easy to mix. The molar number of hydrochloric acid as an acidic catalyst can be about 0.001 to 0.005 times the molar number of the silicon-containing hydrophobic monomer, which is used to adjust the pH of the mixture to ≤1. The molar number of the HEMA monomer can be between about 1 and 3 times the molar concentration of TRIS. In addition, regarding the reaction conditions of each reaction, the reaction temperature of the substitution and hydrolysis reactions can be about 25°C to 40°C and the reaction time is about 3 to 12 hours; the reaction temperature of the condensation reaction is about 50°C to 80°C and the reaction time is about 3 to 12 hours.

[0056] In a third embodiment, a method for preparing a silicon-containing prepolymer is provided, wherein the silicon-containing prepolymer of the present invention is prepared by the same steps as described in the first embodiment, except that the types of components of each reaction can use other silicon-containing hydrophobic monomers and hydroxyl-containing hydrophilic compounds, and the amount of components and hydrochloric acid used and the reaction time can be changed differently. In addition to the TRIS and HEMA monomers used in the first and second embodiments, as described above, in the reaction mechanism of the sol-gel method of the present invention, the substitution hydrolysis reaction is mainly based on the silicon-oxygen silicon group (Si-O-Si) in the structure of the silicon-containing hydrophobic monomer. Based on the above concept, for example, the silicon-containing hydrophobic monomer in the method for preparing the silicon-containing prepolymer of the present invention can use a compound having the following structural formula:

[0057]

[0058] wherein R1 is independently selected from a free radical polymerizable group, such as an acrylamide group, a methacrylic acid group, a methacrylamide group, or a methacryloxy group; R2 is independently selected from a C0-C6 alkyl group, such as a hydroxypropoxypropane group; R3 and R4 are independently selected from a C0-C6 alkyl group; R5, R6, and R7 are each independently selected from a C0-C3 alkyl group;

[0059] and n is an integer of 1 to 3. For example, examples of silicon-containing hydrophobic monomers include: methacryloxypropyl tris(trimethylsiloxy)silane, (3-methacrylamidepropyl)bis(trimethylsiloxy)silane, bis(trimethylsiloxy)silylpropylglycerol methyl methacrylate, acrylamidepropyl tris(trimethoxysiloxy)silane; and hydroxyl-containing hydrophilic compounds may also be hydroxyethyl methacrylate (HEMA), hydroxybutyl methacrylate, monomethacrylate glyceryl, bis(trimethylsiloxy)silylpropylglycerol methyl methacrylate), hydroxypropyl methacrylate, 4-hydroxybutyl acrylate, 2-hydroxybutyl acrylate, or PEG.

[0060] In the hydrolysis reaction of the silicon-containing hydrophobic monomer and water, the molar number of water can be at least about one time, preferably three times, the molar number of the silicon-containing hydrophobic monomer, so that the silicon-containing hydrophobic monomer can be fully hydrolyzed. Generally, the molar number of water can reach the effect of hydrolyzing the silicon-containing hydrophobic monomer when it is about 1 to 20 times the molar number of the silicon-containing hydrophobic monomer. The molar number of ethanol as a co-solvent can be adjusted between about 1 and 20 times the molar number of the silicon-containing hydrophobic monomer, so that water and the silicon-containing hydrophobic monomer are easy to mix. The molar number of hydrochloric acid as an acidic catalyst can be about 0.001 to 0.005 times the molar number of the silicon-containing hydrophobic monomer, which is used to adjust the pH of the mixture to ≤1. The molar number of the hydrophilic compound containing hydroxyl groups can be between about 1 and 3 times the molar concentration of the silicon-containing hydrophobic monomer. In addition, regarding the reaction conditions of each reaction, the reaction temperature of the substitution and hydrolysis reactions can be about 25°C to 40°C and the reaction time is about 3 to 12 hours; the reaction temperature of the condensation reaction is about 50°C to 80°C and the reaction time is about 3 to 12 hours.

[0061] Furthermore, in any of the above-mentioned method steps of the present invention, in addition to using ethanol as a co-solvent, solvents such as alcohols such as methanol, ethanol, isopropanol, acetone, or tetrahydrofuran may also be used.

[0062] Preparation of silicone hydrogel films

[0063] The silicon-containing prepolymer prepared by the method for preparing a silicone hydrogel film of the present invention can be used to prepare a silicone hydrogel film with high water content, oxygen permeability and transparency, and the silicone hydrogel film can be used in the preparation of contact lenses.

[0064] In the method for preparing the silicone hydrogel film proposed in the present invention, the hydrophilic silicon-containing prepolymer prepared by the method for preparing the hydrophilic silicon-containing prepolymer according to the present invention is used as a material, and at least a hydrophilic monomer, at least a cross-linking agent and at least a silicon-containing hydrophobic monomer are added to carry out a polymerization reaction to prepare the silicone hydrogel film.

[0065] See also Figure 2, which shows the method for preparing a silicone hydrogel film according to the present invention, preparing

[0066] The method comprises the following steps:

[0067] Step 210: Mixing the silicon-containing prepolymer prepared in any embodiment of the method for preparing the silicon-containing prepolymer of the present invention with at least a hydrophilic monomer, at least a cross-linking agent, and at least a silicon-containing hydrophobic monomer in weight percentage to obtain a mixed solution;

[0068] Step 220: adding a certain amount of initiator to the mixed solution in step 210, and obtaining a reactant solution after uniform stirring;

[0069] Step 230: Inject the reactant solution into the polypropylene mold, press the upper and lower covers tightly and avoid the generation of bubbles that affect the integrity of the silicone hydrogel.

[0070] Step 240: irradiating with a UV mercury lamp with an illumination of 5 mW to perform photocuring molding with an exposure time of 30 minutes to form a thin film;

[0071] Step 250: first soak the film in a 50% alcohol aqueous solution for 30 minutes to demould, then put it into a fresh 50% alcohol aqueous solution to extract unreacted products for 1 hour, and then soak it in deionized water for 30 minutes to wash away residual alcohol; and

[0072] Step 260: Place the film in a sterilizer and sterilize at 121° C. for 30 minutes to obtain a silicone hydrogel film.

[0073] In the above-mentioned method for preparing the silicone hydrogel film of the present invention, the types and amounts of each component can be prepared in various combinations. For example, the content of the silicon-containing prepolymer can account for about 5 to 20 wt % of the silicone hydrogel film. The content of the hydrophilic compound can account for about 23 to 38 wt % of the silicone hydrogel film. The rest is the content of the crosslinking agent, which is obtained by deducting the amount of the silicon-containing prepolymer and the hydrophilic compound from the total amount of the silicone hydrogel film.

[0074] The hydrophilic monomer component in the silicone hydrogel film can be at least one of a hydroxyl-containing hydrophilic compound, dimethacrylate (DMA) and ethylene glycol methacrylate (PEGMA), and the hydroxyl-containing hydrophilic compound can be the same as or different from the hydroxyl-containing hydrophilic compound used in the prepolymer preparation method of the present invention, that is, the hydroxyl-containing hydrophilic compound can be HEMA, hydroxybutyl methacrylate, glyceryl monomethacrylate, di(trimethylsiloxy)silylpropylglyceryl methyl methacrylate, hydroxypropyl methacrylate, 4-hydroxybutyl acrylate, 2-hydroxybutyl acrylate or PEG.

[0075] The crosslinking agent can be a crosslinking agent commonly used in the preparation of gel films in the art. Any polymer having more than double bonds can be used as a crosslinking agent, for example, triethylene glycol dimethacrylate (TEGDMA) can be used. Alternatively, the prepolymer of the present invention itself can also serve as a crosslinking agent. In the preparation of gel films, when the prepolymer of the present invention is used as a crosslinking agent, other crosslinking agents may or may not be added separately.

[0076] Application Example 1

[0077] The silicone hydrogel film of the present invention is prepared by the steps of the above preparation method, and the materials used may include the silicon-containing prepolymer of the present invention, HEMA, DMA, TEGDMA, PEGMA and SIGMA, wherein the weight percentages of the components are 5wt%, 38wt%, 25wt%, 4wt%, 10wt% and 18wt%, respectively. In addition, UV184 can be used as an initiator, and the amount of UV184 is 2wt%.

[0078] Application Example 2

[0079] The silicone hydrogel film of the present invention is prepared by the steps described in the above preparation method. The materials used may include the silicon-containing prepolymer of the present invention, HEMA, DMA, TEGDMA, PEGMA and SIGMA, wherein the weight percentage of each component is 10wt%, 33wt%, 25wt%, 4wt%, 10wt% and 18wt%, respectively, and the amount of the initiator UV184 used is 2wt%.

[0080] Application Example 3

[0081] The silicone hydrogel film of the present invention is prepared by the steps described in the above preparation method. The materials used may include the silicon-containing prepolymer of the present invention, HEMA, DMA, TEGDMA, PEGMA and SIGMA, wherein the weight percentage of each component is 15wt%, 28wt%, 25wt%, 4wt%, 10wt% and 18wt%, respectively, and the amount of the initiator UV184 used is 2wt%.

[0082] Application Example 4

[0083] The silicone hydrogel film of the present invention is prepared by the steps described in the above preparation method. The materials used may include the silicon-containing prepolymer of the present invention, HEMA, DMA, TEGDMA, PEGMA and SIGMA, wherein the weight percentage of each component is 20wt%, 23wt%, 25wt%, 4wt%, 10wt% and 18wt%, respectively, and the amount of the initiator UV184 used is 2wt%.

[0084] Comparative Example

[0085] In order to understand the effect of the silicone hydrogel film made of the prepolymer formula of the present invention on the oxygen permeability, contact angle, water content, cytotoxicity, etc. of the hydrogel, a group of silicone hydrogels made by adding the same proportion of TRIS monomers that have not been processed by the sol-gel method were compared with silicone hydrogels made by adding prepolymers. The comparative example is to prepare the silicone hydrogel by the same steps as the application example 4, the difference being that the silicone prepolymer of the present invention is replaced by TRIS monomer, wherein the contents of each component - TRIS monomer, HEMA, DMA, TEGDMA, PEGMA and SIGMA are 20wt%, 23wt%, 25wt%, 4wt%, 10wt% and 18wt% respectively, and the amount of the initiator UV184 is 2wt%.

[0086] Oxygen permeability test of silicone hydrogel

[0087] The oxygen permeability test of silicone hydrogel is conducted by using an oxygen permeability tester (CREATECH, model: 201TPermeomter) to test the oxygen permeability (DK) using the polarography method. The principle of polarography is that oxygen will first dissolve in water and diffuse in the contact lens, and the oxygen generated by the contact lens will be proportional to the amount of current. First, the thickness of the silicone hydrogel film to be tested is measured, and it is soaked in standard salt water before the test, and balanced at room temperature for at least 48 hours, and then balanced at 35°C for at least 2 hours. When measuring the silicone hydrogel film, first place the first film on the polarographic electrode, and record the detected current value after it stabilizes. Then stack the second film on the first film and confirm that it is fixed on the polarographic electrode, measure the current value after it stabilizes, and continue to stack the films according to the above steps, measure the current value after stacking to four films, and use the program to correct for the boundary layer effect (Boundary effect) and edge effect (Edge effect), and calculate the oxygen permeability of the silicone hydrogel film.

[0088] Table 1 shows the oxygen permeability of silicone hydrogels of Application Examples 1 to 4 and Comparative Example. It can be observed that in Application Examples 1 to 4, as the prepolymer content increases, the oxygen permeability of the hydrogel increases accordingly. In addition, it can also be observed that in Application Example 4 and Comparative Example, the prepolymer content in Application Example 4 is the same as the TRIS monomer addition amount in Comparative Example, but the oxygen permeability of Application Example 4 (DK=64) is not only better than the oxygen permeability of Comparative Example (DK=46), but also the largest among all the examples.

[0089] Table 1 Oxygen permeability of application examples and comparative examples

[0090]

[0091] Contact angle test

[0092] The contact angle test of silicone hydrogel is carried out using a contact angle meter (model FTA-125) to detect the hydrophilicity / hydrophobicity or adhesion of the material surface. The surface tension between objects will affect the contact angle of their surface. When a droplet is placed on the surface of a material, the angle formed by the tangent between the material surface and the droplet is called the contact angle. The hydrophilicity and hydrophobicity of the material surface can be evaluated by the size of the contact angle. Usually 90° is used as the judgment standard. When the contact angle is greater than 90°, it is considered a hydrophobic material; when the contact angle is less than 90°, it is a hydrophilic material.

[0093] Generally, when the surface of a silicone hydrogel contact lens is highly hydrophobic, it will lead to protein deposition and lipid adhesion, causing the wearer to feel dry eyes and discomfort. Therefore, good hydrophilicity of the surface of a silicone hydrogel contact lens is very critical.

[0094] Table 2 shows the contact angle and hydrophobicity index of Application Examples 1 to 4 and the Comparative Example. It can be observed from Table 2 that in Application Examples 1 to 4, when the prepolymer content increases, the hydrophobic silicon content also increases, resulting in an increase in the hydrophobicity of the silicone hydrogel, and then, the surface contact angle also shows a trend of increasing. In addition, it can also be observed that in Application Example 4 and the Comparative Example, the prepolymer content in Application Example 4 is the same as the amount of TRIS monomer added in the Comparative Example. As shown in Table 2, the contact angle of the Comparative Example is 92, while Application Example 4 has a lower contact angle (89). The reason may be that the silane group (-Si(CH3)3) on the TRIS monomer structure in the Comparative Example is extremely hydrophobic and has a low surface potential energy, which is easy to transfer to the hydrogel surface. Therefore, traditional silicone hydrogels such as the Comparative Example will have a more hydrophobic surface, resulting in a higher contact angle. The prepolymer of Application Example 4 was hydrolyzed and removed the siloxane group (-OSi(CH3)3) in the structure by the sol-gel method, so that the hydrophobicity of the prepolymer was lower than that of the comparative example. It can be clearly seen from Table 2 that the hydrophobicity index and surface contact angle of Application Example 4 were lower than those of the comparative example. The hydrophobicity index and surface contact angle of Application Examples 1 to 3 were also lower than those of the comparative example.

[0095] Table 2 Contact angles of application examples and comparative examples

[0096]

[0097]

[0098] Cytotoxicity assay

[0099] Contact lenses are applied directly onto the eyes, and the materials must be non-toxic and have good biocompatibility.

[0100] The cytotoxicity test of the silicone hydrogel film of the present invention is to extract and detect the silicone hydrogel sample according to the methods and conditions of ISO 10993-5 and ISO 10993-12 of the International Organization for Standardization, and to determine the cytotoxicity level according to the cytotoxicity determination system of ISO 10993-5, thereby evaluating the biocompatibility of the sample.

[0101] The test groups were the silicone hydrogel film group of Application Example 4 of the present invention, the negative control group, the positive control group and the blank control group. In the silicone hydrogel film group, the silicone hydrogel film was washed under a sterile environment and extracted according to the extraction conditions described in ISO 10993-12.

[0102] cm 2 / 1mL extraction ratio, extracted at 37±1℃ for 24±2 hours; negative control group, PE cling film as material, the PE cling film was washed under sterile environment, extracted according to the same extraction conditions as the silicon prepolymer formula group, and finally filtered with a sterile filter membrane with a pore size of 0.22μm, and the filtrate obtained was used as the negative control group; positive control group, cell culture medium containing 10% DMSO; and blank control group, MEM culture medium containing 10% fetal bovine serum (FBS) was used as the blank control group of L929Cell and the blank control group of SIRC Cell.

[0103] The steps of the cytotoxicity test are as follows:

[0104] 1. Wash the culture dish full of L929 cells / SIRC cells with phosphate buffered saline (PBS), add trypsin, and react at 37°C for five minutes to allow the cells to fall off the culture dish.

[0105] 2. Add the cell suspension with a concentration of 8000 cell / ml into a 96-well plate, add a fixed concentration of cell solution to each well, and culture for 24 hours in an environment containing 5% CO2 and a temperature of 37°C.

[0106] 3. Remove the culture medium from the original wells, add the test sample diluent, and culture for 24 hours in an environment containing 5% CO2 and a temperature of 37°C. The test sample group, positive control group, and negative control group were all repeated three times.

[0107] 4. According to the cytotoxicity assessment system of ISO 10993-5, observe the appearance of cells under a microscope and assign grades.

[0108] 5. Replace the culture medium with 20 μL MTT (cell viability analysis) solution. The MTT reagent is reduced to water-insoluble blue-purple crystalline formazan by the succinate dehydrogenase in the mitochondria of living cells and deposited in the cells. The amount of crystals is proportional to the number of cells, while dead cells do not have this function. Then, the cells are placed in a 37°C incubator containing 5% CO2 for 3 hours. After the blue-purple crystals are formed, the MTT solution is aspirated and 100 μL DMSO is added to dissolve the formazan in the cells. The absorbance value at 570 nm is detected by ELISA.

[0109] 6. The cell survival rate was calculated according to the following formula:

[0110] Cell survival rate (%) = 100 × OD570e / OD570b

[0111] Among them, OD570e is the average absorbance of the test sample, and OD570b is the average absorbance of the blank control group.

[0112] 7. According to ISO 10993-5, if the cell appearance score is lower than level 2 and the cell viability value is higher than 70%, it can be considered as non-cytotoxic.

[0113] Table 3 shows the average cell survival rate of Application Example 4. It can be observed from Table 3 that the cell survival rates of L929 cells and SIRC cells in the silicone hydrogel film group of the present invention are 87.64% and 96.41% respectively, both higher than the non-cytotoxic standard of -70% of ISO 10993-5, that is, under the ISO 10993-5 standard, the silicone hydrogel film of the present invention has no obvious toxic reaction.

[0114] Table 3 Average cell survival rate (%)

[0115]

[0116] In summary, the present invention uses a silicon-containing hydrophobic monomer and a hydroxyl-containing hydrophilic compound as materials, and utilizes a hydrolysis / condensation reaction in the presence of a co-solvent in an acidic environment to form a hydrophilic silicon-containing prepolymer. The preparation process is simple, and the hydrophilic silicon-containing prepolymer prepared by the method of the present invention overcomes the hydrophobicity and phase separation problems of the siloxane structure in the conventional technology. At the same time, the silicone hydrogel prepared from the hydrophilic silicone prepolymer not only has an improved oxygen permeability, but also has better hydrophilicity, biocompatibility, etc. than the conventional silicone hydrogel, which effectively overcomes the defects of the conventional technology.

[0117] The embodiments described above are only for illustrating the technical ideas and features of the present invention, and their purpose is to enable people skilled in the art to understand the contents of the present invention and implement them accordingly. They cannot be used to limit the scope of the present invention. That is, any equivalent changes or modifications made according to the spirit disclosed in the present invention should still be included in the scope of the present invention.

Claims

1. A method for preparing a silicon-containing prepolymer, comprising: Mixing water, a co-solvent and a silicon-containing hydrophobic monomer in a molar ratio to form a mixture; adding hydrochloric acid as an acidic catalyst to the mixture to carry out substitution and hydrolysis reactions to obtain substitution and hydrolysis products, wherein the molar concentration of the hydrochloric acid is 0.001 to 0.005 times the molar concentration of the silicon-containing hydrophobic monomer, so that the pH of the mixture is ≤1; and Adding a hydroxyl-containing hydrophilic compound to the substituted and hydrolyzed product to carry out a condensation reaction to obtain the silicon-containing prepolymer, wherein the mole number of the water is 1 to 20 times the mole number of the silicon-containing hydrophobic monomer; the mole number of the co-solvent is 1 to 20 times the mole number of the silicon-containing hydrophobic monomer; The co-solvent is one of methanol, ethanol, isopropanol, acetone and tetrahydrofuran (THF); and the silicon-containing hydrophobic monomer is a silicon-containing hydrophobic monomer containing a siloxane group (Si—O—Si).

2. The method according to claim 1, wherein the molar number of the hydroxyl-containing hydrophilic compound is 1 to 3 times the molar number of the silicon-containing hydrophobic monomer; the reaction temperature of the substitution and hydrolysis reaction is 25° C. to 40° C., and the reaction time of the substitution and hydrolysis reaction is 3 to 12 hours; the reaction temperature of the condensation reaction is 50° C. to 80° C., and the reaction time of the condensation reaction is 3 to 12 hours; and the hydroxyl-containing hydrophilic compound is one of hydroxyethyl methacrylate (HEMA), hydroxybutyl methacrylate, glyceryl monomethacrylate, di(trimethylsiloxy)silylpropylglyceryl methyl methacrylate), hydroxypropyl methacrylate, 4-hydroxybutyl acrylate, 2-hydroxybutyl acrylate and polyethylene glycol (PEG).

3. The method according to claim 2, wherein the silicon-containing hydrophobic monomer is a compound having the following structural formula: Wherein R1 is independently selected from a free radical polymerizable group, and the free radical polymerizable group includes acrylamide, methacrylic acid, methacrylamide, and methacryloxy; R2 is independently selected from a C0-C6 alkyl group; R3 and R4 are independently selected from a C0-C6 alkyl group; R5, R6 and R7 are each independently selected from a C0-C3 alkyl group; and n is an integer of 1 to 3.

4. The method according to claim 3, wherein the silicon-containing hydrophobic monomer is one of methacryloxypropyl tris(trimethylsiloxy)silane, (3-methacrylamidepropyl)bis(trimethylsiloxy)silane, bis(trimethylsiloxy)silylpropyl glycerol methyl methacrylate, and acrylamidopropyl tris(trimethoxysiloxy)silane. The method according to claim 2 , wherein the molar ratio of the water, the co-solvent and the silicon-containing hydrophobic monomer is 3:3:

1.

6. The method according to claim 1, further comprising: The silicon-containing prepolymer was concentrated under reduced pressure at 60°C.

7. A silicone hydrogel film, which is made from a silicon-containing prepolymer prepared by the method according to any one of claims 1 to 6.

8. The silicone hydrogel film according to claim 7, wherein the silicone hydrogel film further comprises at least a second hydrophilic monomer, at least a cross-linking agent, and at least a second silicon-containing hydrophobic monomer.

9. The silicone hydrogel film according to claim 8, wherein the at least second hydrophilic monomer is at least one of a second hydroxyl-containing hydrophilic compound, dimethacrylate (DMA) and ethylene glycol methacrylate (PEGMA), wherein the second hydroxyl-containing hydrophilic compound is one of hydroxyethyl methacrylate (HEMA), hydroxybutyl methacrylate, glyceryl monomethacrylate, di(trimethylsiloxy)silylpropylglyceryl methyl methacrylate, hydroxypropyl methacrylate, 4-hydroxybutyl acrylate, 2-hydroxybutyl acrylate and polyethylene glycol (PEG); the at least cross-linking agent is at least one of the second hydroxyl-containing hydrophilic compound, dimethacrylate (DMA) and ethylene glycol methacrylate (PEGMA); At least one of a silicon prepolymer and triethylene glycol dimethacrylate (TEGDMA); the at least second silicon-containing hydrophobic monomer is 3-methacryloxypropylbis(trimethylsiloxy)methylsilane (SIGMA); the content of the silicon-containing prepolymer accounts for 5 to 20wt% of the silicone hydrogel film, and the content of the second hydroxyl-containing hydrophilic compound accounts for 23 to 38wt% of the silicone hydrogel film; and the silicone hydrogel film is prepared by curing and molding the silicon-containing prepolymer, the at least second hydrophilic monomer, the at least cross-linking agent and the at least second silicon-containing hydrophobic monomer.

10. A method for preparing a silicon-containing prepolymer, comprising: Under an acidic environment containing hydrochloric acid as an acidic catalyst, a substitution and hydrolysis reaction of water, a co-solvent and a silicon-containing hydrophobic monomer is carried out to obtain a substitution and hydrolysis product, wherein the molar number of the hydrochloric acid is 0.001 to 0.005 times the molar number of the silicon-containing hydrophobic monomer; and Carrying out a condensation reaction between a hydroxyl-containing hydrophilic compound and the substitution and hydrolysis product to obtain the silicon-containing prepolymer, wherein the molar number of the water is 1 to 20 times the molar number of the silicon-containing hydrophobic monomer; the molar number of the co-solvent is 1 to 20 times the molar number of the silicon-containing hydrophobic monomer; The co-solvent is one of methanol, ethanol, isopropanol, acetone and tetrahydrofuran (THF); and the silicon-containing hydrophobic monomer is a silicon-containing hydrophobic monomer containing a siloxane group (Si—O—Si).

11. The method according to claim 10, wherein the molar number of the hydroxyl-containing hydrophilic compound is 1 to 3 times the molar number of the silicon-containing hydrophobic monomer; the reaction temperature of the substitution and hydrolysis reaction is 25° C. to 40° C., and the reaction time of the substitution and hydrolysis reaction is 3 to 12 hours; the reaction temperature of the condensation reaction is 50° C. to 80° C., and the reaction time of the condensation reaction is 3 to 12 hours; the hydroxyl-containing hydrophilic compound is selected from hydroxyethyl methacrylate (HEMA), hydroxybutyl methacrylate, glyceryl monomethacrylate, di(trimethylsiloxy)silylpropylglyceryl methyl methacrylate), hydroxypropyl methacrylate, 4-hydroxybutyl acrylate, 2-hydroxybutyl acrylate and polyethylene glycol (PEG); the molar ratio of the water, the co-solvent and the silicon-containing hydrophobic monomer is 3:3:1; and the pH of the acidic environment is ≤1.

12. The method according to claim 11, wherein the silicon-containing hydrophobic monomer is a compound having the following structural formula: Wherein R1 is independently selected from a free radical polymerizable group, and the free radical polymerizable group includes acrylamide, methacrylic acid, methacrylamide, and methacryloxy; R2 is independently selected from a C0-C6 alkyl group; R3 and R4 are independently selected from a C0-C6 alkyl group; R5, R6 and R7 are each independently selected from a C0-C3 alkyl group; and n is an integer of 1 to 3.

13. The method according to claim 12, wherein the silicon-containing hydrophobic monomer is one of methacryloxypropyl tris(trimethylsiloxy)silane, (3-methacrylamidepropyl)bis(trimethylsiloxy)silane, bis(trimethylsiloxy)silylpropyl glycerol methyl methacrylate, and acrylamidopropyl tris(trimethoxysiloxy)silane.

14. A silicone hydrogel film, which is prepared from a silicon-containing prepolymer prepared by the method according to claim 10 or claim 11.

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