CN116687661A - Aqueous humor drainage device and preparation method thereof - Google Patents

Abstract

The invention provides an aqueous humor drainage device and a preparation method thereof, and relates to the technical field of medical appliances; the aqueous humor drainage device is in a tubular structure; is prepared from thiol-ene material by a photo-curing method; the thiol material in the thiol-ene material is at least one selected from DT1, DT2, siTSH, TTTSH and dithiothreitol; the olefinic materials include a first olefinic material and a second olefinic material; the first olefinic material is maleic anhydride modified mitomycin; the second material is at least one selected from triene1, triene2, triene3, triene4 and vinyl gelatin. The aqueous humor drainage device provided by the invention is prepared from the thiol-ene material with good compatibility by a photocuring method, and the aqueous humor drainage device prepared from the material does not degrade in the use process while ensuring the biocompatibility because the material does not contain degradable groups, so that the stability of the aqueous humor drainage device structure is improved.

Description

Aqueous humor drainage device and preparation method thereof

technical field

The invention relates to the technical field of medical devices, in particular to an aqueous humor drainage device and a preparation method thereof.

Background technique

Glaucoma is the second leading cause of blindness and the first irreversible cause of blindness in the world. In 2005, WHO data showed that there were more than 70 million glaucoma patients in the world, and the global blindness rate caused by glaucoma was 8%. In 2020, there will be more than 3.3 million glaucoma patients in the United States, of which 2.7 million patients over the age of 40 suffer from the most common form of open-angle glaucoma. The overall annual expenditure on glaucoma treatment in the United States exceeds 2.86 billion US dollars. It is estimated that there will be more than 4.2 million glaucoma patients in the United States in 2030 In 2050, there will be more than 6.3 million glaucoma patients in the United States. The "Guidelines for Glaucoma in China 2020" mentioned that "it is estimated that the number of glaucoma patients in my country will reach 21 million in 2020, and the number of blind patients will reach 5.67 million." The incidence rate of glaucoma in my country is 0.68% in the general population, and the incidence rate is getting higher and higher with age, and it can reach 4%-7% after the age of 65. With the aging process, the birth of new technologies and the improvement of detection rate, the group of glaucoma patients will further expand.

For the treatment of glaucoma, the principle has always been to reduce the intraocular pressure, prevent or slow down the damage of the patient's optic nerve as much as possible, and preserve the existing vision. When the effect of traditional drug treatment is not good, or the patient cannot tolerate long-term medication, laser trabeculoplasty can be used for treatment; when laser trabeculoplasty treatment cannot reduce the intraocular pressure to a safe range or the maximum tolerated drug treatment fails , Minimally invasive glaucoma surgery (MIGS) with implantation of an aqueous humor drainage device can be performed; MIGS refers to improving the outflow of aqueous humor through various methods on the premise of not damaging the conjunctiva and sclera as much as possible, and finally achieving the goal of reducing intraocular pressure. The advantages of MIGS devices are very prominent. Firstly, there is little damage to the tissue, and the postoperative adverse reactions are small. It can be used for patients with open-angle glaucoma or combined with other surgical methods (phacoemulsification surgery) for the treatment of refractory, Or more complicated glaucoma. MIGS is especially suitable for patients with mild to moderate glaucoma. The biggest feature of this surgical method is its good safety.

As a permanent implant, the aqueous humor diverter not only requires good biocompatibility, but also needs to maintain structural stability.

Existing aqueous humor drainage devices are mainly made of metal materials and synthetic polymer materials; among them, the biocompatibility of metal materials is poor. In order to ensure good biocompatibility, degradable polymer materials are mostly used for preparation, but Degradation of biocompatible polymer materials will lead to insufficient structural stability.

In view of this, it is an urgent technical problem to provide an aqueous humor drainage device that can have both biocompatibility and structural stability.

Contents of the invention

The technical problem to be solved by the present invention is: in order to solve the problem that the aqueous humor drainage device is difficult to have both biocompatibility and structural stability in the prior art, the present invention provides an aqueous humor drainage device, which is made of sulfur Alcohol-ene materials are prepared by photo-curing method. Because thiol-ene materials have good biocompatibility and do not contain degradable groups in the material, it can take into account the biocompatibility and Structural stability, thereby solving the problem that the aqueous humor drainage device in the prior art is difficult to have both biocompatibility and structural stability.

The technical solution adopted by the present invention to solve its technical problems is:

An aqueous humor diversion device, in a tubular structure; the aqueous humor diversion device is prepared from a thiol-ene material by photocuring; the thiol material in the thiol-ene material is selected from tetrahydrodicyclopentadiene Dimethylthiol, 1,10-decanedithiol, tetra(ethylthiol) silane, 1,3,5-tri(propylthiol) isocyanurate, dithiothreitol At least one; the ene material in the thiol-ene material includes a first ene material and a second ene material; the first ene material is maleic anhydride-modified mitomycin; the second ene material Trimethylolpropane triallyl ether, pentaerythritol triallyl ether, 2,4,6-tri(allyloxy)-1,3,5-trihydrazine, 1,3,5-tri At least one of allyl-1,3,5-triazine-2,4,6(1H,3H,5H)-trione and vinyl gelatin.

Alternatively, the maleic anhydride-modified mitomycin is prepared according to the following method:

Add mitomycin, maleic anhydride and a solvent into a three-neck flask, stir and react at 40° C., and precipitate the reaction product with ethanol to obtain maleic anhydride-modified mitomycin.

Optionally, the molar ratio of the mitomycin to the maleic anhydride is 1:1.

Optionally, the vinyl gelatin is prepared as follows:

Mix the gelatin with water, adjust the pH value to be alkaline, then drop allyl glycidyl ether for reaction, adjust the pH value to neutral, undergo dialysis and freeze-drying successively to obtain vinyl gelatin.

Optionally, the mass ratio of gelatin to allyl glycidyl ether is 20:1.

Optionally, the molar ratio of the first olefinic material to the second olefinic material is (0.1-1):100.

Optionally, the molar ratio of ene material to thiol material in the thiol-ene material is (0.9-0.99):1.

Optionally, the surface of the aqueous humor diverter is also chemically modified by methacryloyl dextran.

Another object of the present invention is to provide a method for preparing the above-mentioned aqueous humor drainage device, which includes the following process: according to the formula amount, mix the thiol material, the ene material, and the photoinitiator, and inject it into the microfluidic mold, The aqueous humor drainage device is obtained by irradiating with ultraviolet light.

Optionally, the following process is also included: adding the aqueous humor diverter into the aqueous solution of methacrylylated dextran, and vibrating at 37° C. to obtain a surface-modified aqueous humor diverter.

The beneficial effects of the present invention are:

The aqueous humor drainage device provided by the present invention is prepared by photocuring a thiol-ene material with good compatibility. Since the material does not contain degradable groups, the aqueous humor drainage device prepared with this material can While ensuring biocompatibility, it will not degrade during use, thereby improving the stability of the structure of the aqueous humor drainage device, so that it can function as a permanent implant; The mitomycin is combined with other ene materials to act as the ene material in the thiol-ene material, and the modified mitomycin (MMC) is introduced into the aqueous humor drainage device. On the one hand, the MMC has a higher effect on fibroblast Biological effects and long-term inhibition can reduce scarring during surgery; on the other hand, avoid the side effects that may be caused by the introduction of MMC through modification; thus, by introducing the modified MMC into the aqueous humor drainage device, both It reduces the toxicity of MMC and reduces the scarring of the surgical site after surgery.

Description of drawings

The present invention will be further described below in conjunction with the accompanying drawings and embodiments.

Fig. 1 is the ¹ H NMR spectrogram of raw material gelatin in the present invention;

Fig. 2 is the ¹ H NMR spectrogram of vinyl gelatin in the present invention;

Fig. 3 is the nuclear magnetic spectrum figure of MMC among the present invention;

Fig. 4 is the nuclear magnetic spectrum figure of MMC-MA among the present invention;

Fig. 5 is the infrared spectrogram of MMC among the present invention;

Fig. 6 is an infrared spectrogram of MMC-MA in the present invention.

Detailed ways

The present invention will now be described in further detail. The embodiments described below are exemplary and are intended to be used to explain the present invention, but not to be construed as limitations to the present invention. Based on the embodiments of the present invention, those of ordinary skill in the art obtained without creative work All other embodiments belong to the protection scope of the present invention.

In the description of the present invention, it should be understood that the terms "first" and "second" are only used to simplify the description, and cannot be understood as indicating or implying relative importance, or implicitly indicating the number of indicated technical features . Thus, a feature defined as "first" or "second" may explicitly or implicitly include one or more of these features. In the description of the present invention, "plurality" means two or more, unless otherwise specifically defined.

In order to solve the problem that the aqueous humor drainage device is difficult to have both biocompatibility and structural stability in the prior art, the present invention provides an aqueous humor drainage device in a tubular structure, that is, the aqueous humor drainage device is in a tubular shape as a whole, and its There is a drainage channel inside, so that the aqueous humor in the patient's eye can be drained to the subconjunctival space through the drainage channel, thereby reducing the intraocular pressure of glaucoma patients; it should be noted that the specific shape, structure, size, etc. of the aqueous humor drainage device All can be selected according to actual needs or corresponding existing technologies; the internal drainage channels can be equal-diameter drainage channels, or non-equal-diameter drainage channels.

In order to take into account the biocompatibility and structural stability of the aqueous humor drainage device, the present invention preferably prepares the aqueous humor drainage device from a thiol-ene material through a photocuring method. Specifically, the present invention preferably selects the aqueous humor drainage device from The thiol-ene material is prepared by adding a photoinitiator through microfluidics combined with photocuring; further, the thiol material in the thiol-ene material is preferably selected from tetrahydrodicyclopentadiene dimethyl mercaptan (DT1), 1,10-decanedithiol (DT2), tetrakis (ethylthiol) silane (SiTSH), 1,3,5-tris (propylthiol) isocyanurate (TTTSH), At least one of dithiothreitol; preferably the ene material in the thiol-ene material includes a first ene material and a second ene material; wherein the first ene material is maleic anhydride-modified mitomycin (MMC -MA); the second alkene material is selected from trimethylolpropane triallyl ether (triene1), pentaerythritol triallyl ether (triene2), 2,4,6-tri(allyloxy)-1, 3,5-trihydrazine (triene3), 1,3,5-triallyl-1,3,5-triazine-2,4,6(1H,3H,5H)-trione (triene4), ethylene At least one of gelatin bases.

The aqueous humor drainage device provided by the present invention is prepared by photocuring a thiol-ene material with good compatibility. Since the material does not contain degradable groups, the aqueous humor drainage device prepared with this material can While ensuring biocompatibility, it will not degrade during use, thereby improving the stability of the structure of the aqueous humor drainage device, so that it can function as a permanent implant; The mitomycin is combined with other ene materials to act as the ene material in the thiol-ene material, and the modified mitomycin (MMC) is introduced into the aqueous humor drainage device. On the one hand, the MMC has a higher effect on fibroblast Biological effects and long-term inhibition can reduce scarring during surgery; on the other hand, avoid the side effects that may be caused by the introduction of MMC through modification; thus, by introducing the modified MMC into the aqueous humor drainage device, both It reduces the toxicity of MMC and reduces the scarring of the surgical site after surgery.

Specifically, the structural formulas of DT1, DT2, SiTSH, and TTTSH in the present invention are shown in the following formulas:

Among the present invention, the structural formulas of triene1, triene2, triene3, and triene4 are shown in the following formula respectively:

The preferred maleic anhydride modified mitomycin of the present invention is prepared according to the following method:

Add mitomycin, maleic anhydride and a solvent into a three-neck flask, stir and react at 40° C., and precipitate the reaction product with ethanol to obtain maleic anhydride-modified mitomycin.

The reaction formula of this preparation method is as follows:

In the present invention, the preferred solvent in the preparation method is tetrahydrofuran; the preferred molar ratio of mitomycin to maleic anhydride is 1:1; and the yield of MMC-MA in the preparation method can reach 78%.

The preferred vinyl gelatin of the present invention is prepared according to the following method:

Mix the gelatin with water, adjust the pH value to be alkaline, then drop allyl glycidyl ether for reaction, adjust the pH value to neutral, undergo dialysis and freeze-drying successively to obtain vinyl gelatin.

The reaction formula of this preparation method is as follows:

In the above-mentioned preparation process of the present invention, after gelatin is mixed with water, the pH value of the solution is adjusted to 10.50 with a sodium hydroxide aqueous solution with a concentration of 3 mol/L; /L hydrochloric acid solution to adjust the pH value to neutral; the mass ratio of gelatin to allyl glycidyl ether is preferably 20:1 in the present invention.

In order to reduce the scarring of the surgical site while taking into account the compatibility and structural stability of the aqueous humor drainage device, the molar ratio of the first ene material to the second ene material is preferably (0.1-1): 100; thiol is preferred - The molar ratio of the ene material to the thiol material in the ene material is (0.9-0.99):1.

Further, the present invention preferably prepares the aqueous humor diverter by adding photoinitiators diphenyl-(2,4,6-trimethylbenzoyl)phosphine (TPO), 1-hydroxycyclohexylbenzene methyl ketone (184), 2-hydroxy-4'-(2-hydroxyethoxy)-2-methylpropiophenone (2959), ethyl 2,4,6-trimethylbenzoylphenylphosphonate At least one of ester (TPO-L), phenylbis(2,4,6-trimethylbenzoyl)phosphine oxide (819) for photocuring; and preferably photoinitiator and thiol-ene material The molar ratio is (0.5-2.5):100.

In addition, it is further preferred in the present invention that the surface of the aqueous humor diverter is also chemically modified by methacrylated dextran (DXM), so as to limit cell adhesion and Diffusion, thereby reducing the risk of blockage of the aqueous humor drain due to cell adhesion.

The structural formula of DXM is as follows:

Another object of the present invention is to provide a method for preparing the above-mentioned aqueous humor drainage device, which includes the following process: according to the formula amount, mix the thiol material, the ene material, and the photoinitiator, and inject it into the microfluidic mold, The aqueous humor drainage device is obtained by irradiating with ultraviolet light.

The preparation method of the aqueous humor drainage device provided by the present invention is prepared by photocuring a thiol-ene material with good compatibility. Since the material does not contain degradable groups, the aqueous humor prepared from this material While ensuring biocompatibility, the diverter will not degrade during use, thereby improving the stability of the aqueous humor diverter structure and enabling it to function as a permanent implant; through the use of microfluidics and overmolding Technology, optimize processing technology, improve production efficiency, and facilitate mass production.

Further, the preparation method of the aqueous humor drainage device provided by the present invention also includes the following process: adding the aqueous humor drainage device to the aqueous solution of methacrylated dextran, and shaking at 37°C to obtain a surface-modified aqueous humor drainage device. Water diverter.

The present invention preferably has a mass fraction of methacrylated dextran aqueous solution of 15%; by modifying methacrylated dextran on the surface of the aqueous humor drainage device, cell adhesion and diffusion can be limited, thereby reducing the risk of cell adhesion. Risk of blockage of the aqueous humor drain.

In order to make the above objects, features and advantages of the present invention more comprehensible, specific embodiments of the present invention will be described in detail below in conjunction with the accompanying drawings.

In the absence of special instructions, the vinyl gelatin in each embodiment of the present invention and comparative examples is prepared according to the following method:

In a round-bottom flask (100 ml) equipped with a thermometer, a stirrer and a reflux condenser, add 5.935 g of gelatin and 60 ml of water, adjust the pH value of the solution to 10.50 with a concentration of 3 mol L ^-1 aqueous sodium hydroxide solution, and then Add 0.29675 g of allyl glycidyl ether dropwise, react for 4 hours, adjust the pH of the reaction mixture to neutral with hydrochloric acid with a concentration of 3 mol L ^-1 , dialyze for 3 days, and freeze-dry to obtain vinyl gelatin.

Figure 1 and Figure 2 are the ¹ H NMR spectra of the raw material gelatin and vinyl gelatin respectively. Comparing Figure 1 and Figure 2, it can be seen that vinyl gelatin has new vinyl peaks at δ=5.35ppm and 5.75ppm.

In the absence of special instructions, the maleic anhydride-modified mitomycin in each embodiment of the present invention and comparative examples is prepared according to the following method:

Add 1 mol of mitomycin (MMC), 1 mol of maleic anhydride and 100 ml of solvent tetrahydrofuran into a three-necked flask, stir at 40°C for 7 hours, and precipitate the reaction product with ethanol to obtain maleic anhydride-modified mitomycin (MMC-MA) with a yield of 78%.

Fig. 3 and Fig. 4 are respectively the NMR spectra of the raw material MMC of the present invention and the mitomycin (MMC-MA) of maleic anhydride modification, by comparing Fig. 3 and Fig. 4, MMC-MA is at δ=5.65ppm , 5.83ppm, 6.27ppm new characteristic peaks after ring opening of maleic anhydride appeared.

The infrared spectrograms of raw material MMC and maleic anhydride-modified mitomycin (MMC-MA) in the present invention are shown in Fig. 5 and Fig. 6 respectively.

Example 1

This embodiment provides an aqueous humor drainage device, the preparation method of which is as follows:

Mix 1 mol of dithiothreitol, 0.9 mol of vinyl gelatin, 0.009 mol of maleic anhydride-modified mitomycin MMC-MA and 0.005 mol of initiator TPO, inject it into the microfluidic mold, and pass ultraviolet rays with a wavelength of 355nm Light irradiated for 30s to obtain an aqueous humor diverter; then add the aqueous humor diverter to a 15% methacrylylated dextran (DXM) aqueous solution, shake at 37°C for 7 days, and obtain a surface-modified Aqueous drainage device.

Example 2

This embodiment provides an aqueous humor drainage device, the preparation method of which is as follows:

Inject 0.5mol dithiothreitol, 0.5mol DT1, 0.99mol vinyl gelatin, 0.0099mol maleic anhydride-modified mitomycin MMC-MA, and 0.025mol initiator 184 into the microfluidic mold. The aqueous humor diverter was obtained by irradiating with 355nm ultraviolet light for 30s; the aqueous humor diverter was then added to 15% methacrylylated dextran (DXM) aqueous solution, and shaken at 37°C for 7 days to obtain Surface-modified aqueous humor diverters.

Example 3

This embodiment provides an aqueous humor drainage device, the preparation method of which is as follows:

0.5mol dithiothreitol, 0.5mol TTTSH, 0.45mol vinyl monomer riene1, 0.45mol vinyl gelatin, 0.0095mol maleic anhydride modified mitomycin MMC-MA, 0.01mol initiator TPO-L , injected into the microfluidic mold, and irradiated by ultraviolet light with a wavelength of 355nm for 30s to obtain an aqueous humor drainage device; then add the aqueous humor drainage device to a 15% mass fraction of dextran methacryl (DXM) aqueous solution , shaking at 37°C for 7 days to obtain a surface-modified aqueous humor diverter.

Comparative example 1

This comparative example provides an aqueous humor drainage device, the preparation method of which is as follows:

Mix 1.5mol dithiothreitol, 0.9mol vinyl gelatin, 0.009mol maleic anhydride-modified mitomycin MMC-MA and 0.005mol initiator TPO, inject it into the microfluidic mold, pass UV light was irradiated for 30s to obtain an aqueous humor diverter; then the aqueous humor diverter was added to a 15% mass fraction of methacrylated dextran (DXM) aqueous solution, and shaken at 37°C for 7 days to obtain a surface-modified aqueous humor diverter.

Comparative example 2

This comparative example provides an aqueous humor drainage device, the preparation method of which is as follows:

Mix 0.5mol dithiothreitol, 0.9mol vinyl gelatin, 0.009mol maleic anhydride-modified mitomycin MMC-MA and 0.005mol initiator TPO, inject it into the microfluidic mold, and pass the UV light was irradiated for 30s to obtain an aqueous humor diverter; then the aqueous humor diverter was added to a 15% mass fraction of methacrylated dextran (DXM) aqueous solution, and shaken at 37°C for 7 days to obtain a surface-modified aqueous humor diverter.

Comparative example 3

This comparative example provides an aqueous humor drainage device, the preparation method of which is as follows:

Mix 1 mol of dithiothreitol, 0.909 mol of maleic anhydride-modified mitomycin MMC-MA and 0.005 mol of initiator TPO, inject it into the microfluidic mold, and irradiate it with ultraviolet light with a wavelength of 355nm for 30s, but it cannot be formed Get the aqueous diverter you want.

Comparative example 4

This comparative example provides an aqueous humor drainage device, the preparation method of which is as follows:

Mix 1 mol dithiothreitol, 0.909 mol vinyl gelatin and 0.005 mol initiator TPO, inject it into the microfluidic mold, and irradiate it with ultraviolet light with a wavelength of 355nm for 30s to obtain an aqueous humor drainage device; then drain the aqueous humor The device was added to an aqueous solution of 15% mass fraction of methacryloyl dextran (DXM), and shaken at 37° C. for 7 days to obtain a surface-modified aqueous humor diverter.

Comparative example 5

This comparative example provides an aqueous humor drainage device, the preparation method of which is as follows:

Mix 1 mol of dithiothreitol, 0.9 mol of vinyl gelatin, 0.015 mol of maleic anhydride-modified mitomycin MMC-MA and 0.005 mol of initiator TPO, inject it into the microfluidic mold, and pass ultraviolet rays with a wavelength of 355nm Light irradiated for 120s to obtain an aqueous humor diverter; then add the aqueous humor diverter to a 15% methacrylylated dextran (DXM) aqueous solution, shake at 37°C for 7 days, and obtain a surface-modified Aqueous drainage device.

Comparative example 6

This comparative example provides an aqueous humor drainage device, the preparation method of which is as follows:

Mix 1mol dithiothreitol, 0.9mol gelatin, 0.009mol maleic anhydride-modified mitomycin MMC-MA and 0.005mol initiator TPO, inject into the microfluidic mold, and irradiate with ultraviolet light with a wavelength of 355nm After 30 seconds, the aqueous humor drainage device was obtained; then the aqueous humor drainage device was added to a 15% mass fraction of methacrylylated dextran (DXM) aqueous solution, and shaken at 37°C for 7 days to obtain surface-modified aqueous humor diverter.

Comparative example 7

This comparative example provides an aqueous humor drainage device, the preparation method of which is as follows:

Mix 1 mol dithiothreitol, 0.9 mol vinyl gelatin, 0.009 mol mitomycin MMC and 0.005 mol initiator TPO, inject it into the microfluidic mold, and irradiate it with ultraviolet light with a wavelength of 355 nm for 60 seconds to obtain aqueous humor drainage Then add the aqueous humor diverter to 15% methacryloyl dextran (DXM) aqueous solution, shake at 37° C. for 7 days to obtain a surface-modified aqueous humor diverter.

Comparative example 8

This comparative example provides an aqueous humor drainage device, the preparation method of which is as follows:

Mix 1 mol of dithiothreitol, 0.9 mol of vinyl gelatin, 0.009 mol of maleic anhydride-modified mitomycin MMC-MA and 0.005 mol of initiator TPO, inject it into the microfluidic mold, and pass ultraviolet rays with a wavelength of 355nm Light was irradiated for 30 seconds to obtain an aqueous humor drainage device.

The performance of the aqueous humor drainage device prepared by each embodiment and comparative examples is detected according to the following methods:

Cytostatic effect test:

The effect of cell inhibition was evaluated by the response of the cells. The primary fibroblasts (10 cells/well) were cultured with Falcon medium (DMEM) containing 10% fetal bovine serum. After the fibroblasts have settled, the migration assay inserts the aqueous drain so that it is completely submerged in the medium. After culturing for 5 days, the status of fibroblasts was detected by live/dead staining and CCK-8, and the live/dead ratio of fibroblasts (HTFs) was calculated on day 5. The higher the activity of fibroblasts, the more serious the scarring.

Cell adhesion test:

3T3 mouse embryonic bromocytes were preserved in T-75Falcon cell culture, using sterile Dulbecco's modified Falcon medium (DMEM), containing 10% fetal bovine serum (FBS) and 100 units/ml Penicillin and 0.1 mg/ml streptomycin. Six samples of each covering (total of 36 samples) were placed in a 6-well tissue culture plate and exposed to UV light for 10-15 min. Cells were seeded onto the cover membrane at a density of approximately 11 000 cells/cm. Then the cells were incubated at 37° C. under 5% carbon dioxide for 24 h, and then the culture medium was decanted and gently washed once with PBS. The number of adherent cells was defined as the number of viable cells per 100*field. Percentage of control Adhesion was calculated by multiplying the ratio of the percent viable cells on the treated substrate to the percent viable cells on the untreated substrate by 100. The mean control adhesion rate was determined for each sample group and statistical comparisons for viability assays were performed as described above.

Test of mass loss rate:

The degradation stability test is determined by soaking the sample in 1mol sodium hydroxide at 37°C for more than 1 month at each time point for weight change. The samples consisted of 10 mg mechanically excised cylinders measuring 1.6 mm in diameter and 1.2 mm in height. The dry mass of each sample was measured with 0.1 μg accuracy. At each desired time point, each sample will be removed from the solution, and the polymer surface will be gently dried with an absorbent wipe. Mass loss is the mass of the (PTFE) block measured after the sample is placed on the PTFE; placed in a vacuum oven at 120°C for 24 hours, then the sample is taken out and re-weighed to determine the final mass lost . Mass loss is calculated as the change in mass percent from initial weight to vacuum-dried mass. Data reported are the mean of four samples.

The test results are shown in Table 1:

It can be seen from the data in Table 1 that the aqueous humor diverters prepared in each embodiment of the present invention have excellent structural stability, help reduce scarring, and limit cell adhesion and diffusion.

Compared with Example 1, Comparative Example 1 increased the amount of thiol material in the thiol-ene material. Although the prepared aqueous humor drainage device reduced cell adhesion and reduced the risk of blocking the aqueous humor drainage device, its quality The loss rate increases, and the structural stability of the aqueous humor diverter becomes worse.

Compared with Example 1, comparative example 2 reduces the amount of thiol material added in the thiol-ene material, the adhesion of the cells of the prepared aqueous humor drainage device increases, the risk of blockage of the aqueous humor drainage device increases, and the mass loss rate also decreases. Slightly decreased, the structural stability deteriorated.

Comparative Example 3 Compared with Example 1, only the first ene material MMC-MA was added to the thiol-ene material, and it was difficult to mold according to the molding parameters in Example 1, and the aqueous humor drainage device could not be prepared.

Comparative Example 4 Compared with Example 1, only the second ene material was added to the ene material in the thiol-ene material, and the live/dead ratio of HTFs fibroblasts in the prepared aqueous humor drainage device was significantly increased after 5 days, and the scarring rate was increased. risk; at the same time, cell adhesion is also slightly increased compared with Example 1, and the risk of aqueous humor drainage device blockage is increased.

Compared with Example 1, Comparative Example 5 increased the amount of the first olefin material in the olefin material, and the molding difficulty increased, and the required molding time became longer; although the aqueous humor drainage device could be formed, the prepared aqueous humor drainage device Although the 5-day HTFs fibroblast live/dead ratio decreased and the risk of scarring decreased, the mass loss rate increased and the structural stability deteriorated.

Compared with Example 1, comparative example 6 uses gelatin instead of vinyl gelatin, which cannot be cross-linked to form an aqueous humor drainage device.

In Comparative Example 7, compared with Example 1, MMC was used to replace MMC-MA, the molding difficulty increased, and the required molding time became longer; the prepared aqueous humor drainage device had an increased live/dead ratio of HTFs fibroblasts after 5 days, while MMC did not. Combined in the aqueous humor drainage device in the form of covalent bonds, but filled in the aqueous humor drainage device in the form of blending, which reduces the ability to inhibit scarring for a long time; at the same time, the mass loss rate increases and the stability of the structure deteriorates .

Comparative Example 8 Compared with Example 1, no methacryloyl dextran was used to chemically modify the surface of the aqueous humor drainage device, and the cell adhesion of the prepared aqueous humor drainage device was significantly increased, and at the same time, the HTFs formed fibrils after 5 days The cell live/dead ratio also increased, and the risk of scarring increased compared with Example 1.

Inspired by the above-mentioned ideal embodiment according to the present invention, through the above-mentioned description content, relevant workers can make various changes and modifications within the scope of not departing from the technical idea of the present invention. The technical scope of the present invention is not limited to the content in the specification, but must be determined according to the scope of the claims.

Claims (10)

1. An aqueous humor drainage device is characterized in that it is in a tubular structure; the aqueous humor drainage device is prepared from a thiol-ene material by a photocuring method; the thiol material in the thiol-ene material is selected from From tetrahydrodicyclopentadiene dimethyl mercaptan, 1,10-decanedithiol, tetra(ethyl mercaptan) silane, 1,3,5-tris (propyl mercaptan) isocyanurate, di At least one of thiothreitol; the alkene material in the thiol-ene material includes a first alkene material and a second alkene material; the first alkene material is maleic anhydride-modified mitomycin; The second alkene material is selected from trimethylolpropane triallyl ether, pentaerythritol triallyl ether, 2,4,6-tris(allyloxy)-1,3,5-trihydrazine, 1 , at least one of 3,5-triallyl-1,3,5-triazine-2,4,6(1H,3H,5H)-trione and vinyl gelatin. 2. aqueous humor drainage device as claimed in claim 1, is characterized in that, the mitomycin of described maleic anhydride modification is prepared according to the following method: Add mitomycin, maleic anhydride and a solvent into a three-neck flask, stir and react at 40° C., and precipitate the reaction product with ethanol to obtain maleic anhydride-modified mitomycin. 3. The aqueous humor drainage device according to claim 2, wherein the molar ratio of the mitomycin to the maleic anhydride is 1:1. 4. The aqueous humor drainage device according to claim 1, wherein the vinyl gelatin is prepared according to the following method: Mix the gelatin with water, adjust the pH value to be alkaline, then drop allyl glycidyl ether for reaction, adjust the pH value to neutral, undergo dialysis and freeze-drying successively to obtain vinyl gelatin. 5. The aqueous humor drainage device according to claim 4, wherein the mass ratio of gelatin to allyl glycidyl ether is 20:1. 6. The aqueous humor drainage device according to any one of claims 1-5, wherein the molar ratio of the first vinyl material to the second vinyl material is (0.1-1):100. 7 . The aqueous humor drainage device according to claim 6 , wherein the molar ratio of ene material to thiol material in the thiol-ene material is (0.9-0.99):1. 8. The aqueous humor drainage device according to claim 7, wherein the surface of the aqueous humor drainage device is also chemically modified by methacrylylated dextran. 9. A preparation method of the aqueous humor drainage device as claimed in any one of claims 1-8, characterized in that it comprises the following process: according to the formula amount, thiol material, ene material, photoinitiator are mixed, injected In the microfluidic mold, the aqueous humor drainage device is obtained by irradiating with ultraviolet light. 10. The preparation method of the aqueous humor drainage device as claimed in claim 9, further comprising the following process: adding the aqueous humor drainage device into an aqueous solution of methacrylated dextran, at 37° C. Vibration is performed to obtain a surface-modified aqueous humor diverter.