CN116687661B - Aqueous humor drainage device and preparation method thereof - Google Patents

Abstract

The present invention provides an aqueous humor drainage device and a preparation method thereof, and relates to the technical field of medical devices; the aqueous humor drainage device is in a tubular structure; it is prepared by a thiol-ene material through a photocuring method; the thiol material in the thiol-ene material is selected from at least one of DT1, DT2, SiTSH, TTTSH, and dithiothreitol; the 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 is selected from at least one of triene1, triene2, triene3, triene4, and vinyl gelatin. The aqueous humor drainage device provided by the present invention is prepared by a photocuring method using a thiol-ene material with good compatibility, and since the material does not contain a degradable group, the aqueous humor drainage device prepared by the material will not degrade during use while ensuring biocompatibility, thereby improving the stability of the aqueous humor drainage device structure.

Description

Aqueous humor drainage device and preparation method thereof

Technical Field

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

Background Art

Glaucoma is the second leading cause of blindness in the world 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 were more than 3.3 million glaucoma patients in the United States, of which 2.7 million patients over the age of 40 were troubled by the most common open-angle glaucoma. The overall annual cost of glaucoma treatment in the United States exceeded US$2.86 billion. It is estimated that there will be more than 4.2 million glaucoma patients in the United States in 2030 and more than 6.3 million glaucoma patients in the United States in 2050. The "China Glaucoma Guidelines 2020" mentioned that "it is estimated that the number of glaucoma patients in my country in 2020 may reach 21 million, and the number of blind people may reach 5.67 million". The incidence of glaucoma in my country is 0.68% in the general population. The incidence rate increases with age, and after the age of 65, it can reach 4%-7%. With the aging process, the emergence of new technologies and the increase in detection rates, the glaucoma patient group will further expand.

The treatment of glaucoma has always been based on the principle of reducing intraocular pressure, preventing or slowing down the damage to the patient's optic nerve as much as possible, and preserving existing vision. When traditional drug treatment is ineffective or the patient cannot tolerate long-term medication, laser trabeculoplasty can be used for treatment; when laser trabeculoplasty treatment cannot reduce intraocular pressure to a safe range or 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 aqueous humor outflow through various methods while minimizing damage to the conjunctiva and sclera, ultimately achieving the purpose of reducing intraocular pressure. The advantages of the MIGS device are very prominent. First of all, it causes little damage to tissues and has few adverse reactions after surgery. It can be used for patients with open-angle glaucoma or in combination with other surgical methods (cataract phacoemulsification surgery) to treat 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 drainage device is not only required to have good biocompatibility but also to be able to maintain structural stability.

Existing aqueous humor drains are mainly made of metal materials and synthetic polymer materials; among them, metal materials have poor biocompatibility. In order to ensure good biocompatibility, degradable polymer materials are often used for preparation. However, polymer materials with good biocompatibility will lead to insufficient structural stability due to degradation.

In view of this, providing an aqueous humor drainage device that has both biocompatibility and structural stability is a technical problem that urgently needs to be solved.

Summary 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 in the prior art is difficult to have both biocompatibility and structural stability, the present invention provides an aqueous humor drainage device, which is prepared by a thiol-ene material through a photocuring method. Since the thiol-ene material has good biocompatibility and does not contain degradable groups in the material, the biocompatibility and structural stability of the aqueous humor drainage device can be taken into account, 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 problem is:

A kind of aqueous humor drainage device has a tubular structure; the aqueous humor drainage device is prepared by a thiol-ene material through a photocuring method; the thiol material in the thiol-ene material is selected from at least one of tetrahydrodicyclopentadiene dimethyl mercaptan, 1,10-decandithiol, tetrakis(ethyl mercaptan) silane, 1,3,5-tri(propyl mercaptan) isocyanurate, and dithiothreitol; 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 is selected from at least one of trimethylolpropane triallyl ether, pentaerythritol triallyl ether, 2,4,6-tri(allyloxy)-1,3,5-trihydrazine, 1,3,5-triallyl-1,3,5-triazine-2,4,6(1H,3H,5H)-trione, and vinyl gelatin.

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

Mitomycin, maleic anhydride and a solvent were added into a three-necked flask, stirred and reacted at 40° C., and then the reaction product was precipitated 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:

The gelatin is mixed with water, the pH value is adjusted to alkaline, and then allyl glycidyl ether is dropped into the mixture for reaction, and the pH value is adjusted to neutral. The mixture is dialyzed and freeze-dried to obtain vinyl gelatin.

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

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

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

Optionally, the surface of the aqueous humor drain is also chemically modified by methacryloylating dextran.

Another object of the present invention is to provide a method for preparing the aqueous humor drainage device as described above, comprising the following process: mixing a thiol material, an olefin material, and a photoinitiator according to the formula, injecting the mixture into a microfluidic mold, and irradiating the mold with ultraviolet light to obtain an aqueous humor drainage device.

Optionally, the method further comprises the following process: adding the aqueous humor drainage device into a methacryloylated dextran aqueous solution, and shaking the solution at 37° C. to obtain a surface-modified aqueous humor drainage device.

The beneficial effects of the present invention are:

The aqueous humor drainage device provided by the present invention is prepared by a thiol-ene material with good compatibility through a photocuring method. Since the material does not contain a degradable group, the aqueous humor drainage device prepared by the material will not degrade during use while ensuring biocompatibility, thereby improving the stability of the aqueous humor drainage device structure and enabling it to function as a permanent implant. In addition, the present invention uses maleic anhydride-modified mitomycin combined with other ene materials as the ene material in the thiol-ene material to introduce modified mitomycin (MMC) into the aqueous humor drainage device. On the one hand, the high biological effect and long-term inhibitory effect of MMC on fibroblasts are utilized to reduce scarring during surgery. On the other hand, the side effects that may be caused by the introduction of MMC are avoided through modification. Therefore, by introducing the modified MMC into the aqueous humor drainage device, the toxicity of MMC is reduced and the scarring of the surgical site after surgery is reduced.

BRIEF DESCRIPTION OF THE DRAWINGS

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

FIG1 is a ¹ H NMR spectrum of raw gelatin in the present invention;

FIG2 is a ¹ H NMR spectrum of vinyl gelatin in the present invention;

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

FIG4 is a nuclear magnetic spectrum of MMC-MA in the present invention;

Fig. 5 is an infrared spectrum of MMC in the present invention;

FIG. 6 is an infrared spectrum of MMC-MA in the present invention.

DETAILED DESCRIPTION

The present invention is now further described in detail. The embodiments described below are exemplary and intended to be used to explain the present invention, but cannot be understood as limiting the present invention. All other embodiments obtained by ordinary technicians in this field without creative work based on the embodiments of the present invention belong to the scope of protection 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 should not be understood as indicating or implying relative importance, or implicitly indicating the number of the indicated technical features. Thus, the features defined as "first" and "second" may explicitly or implicitly include one or more of the features. In the description of the present invention, the meaning of "plurality" is two or more, unless otherwise clearly and specifically defined.

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

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 by a photocuring method. Specifically, the present invention preferably prepares the aqueous humor drainage device from a thiol-ene material by adding a photoinitiator through microfluidics combined with a photocuring method; further, the present invention preferably selects the thiol material in the thiol-ene material from tetrahydrodicyclopentadiene dimethyl mercaptan (DT1), 1,10-decanedithiol (DT2), tetrakis(ethyl mercaptan) silane (SiTSH), 1,3,5-tri(propyl mercaptan) isocyanurate (TTTSH), dithiothreitol At least one of; 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 ene material is selected from at least one of 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), and vinyl gelatin.

The aqueous humor drainage device provided by the present invention is prepared by a thiol-ene material with good compatibility through a photocuring method. Since the material does not contain a degradable group, the aqueous humor drainage device prepared by the material will not degrade during use while ensuring biocompatibility, thereby improving the stability of the aqueous humor drainage device structure and enabling it to function as a permanent implant. In addition, the present invention uses maleic anhydride-modified mitomycin combined with other ene materials as the ene material in the thiol-ene material to introduce modified mitomycin (MMC) into the aqueous humor drainage device. On the one hand, the high biological effect and long-term inhibitory effect of MMC on fibroblasts are utilized to reduce scarring during surgery. On the other hand, the side effects that may be caused by the introduction of MMC are avoided through modification. Therefore, by introducing the modified MMC into the aqueous humor drainage device, the toxicity of MMC is reduced and the scarring of the surgical site after surgery is reduced.

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

The structural formulas of triene1, triene2, triene3 and triene4 in the present invention are respectively shown as follows:

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

Mitomycin, maleic anhydride and a solvent were added into a three-necked flask, stirred and reacted at 40° C., and then the reaction product was precipitated with ethanol to obtain maleic anhydride-modified mitomycin.

The reaction formula of the preparation method is as follows:

The invention preferably uses tetrahydrofuran as the solvent in the preparation method; preferably uses 1:1 as the molar ratio of mitomycin to maleic anhydride; and according to calculation, 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:

The gelatin is mixed with water, the pH value is adjusted to alkaline, and then allyl glycidyl ether is dropped into the mixture for reaction, and the pH value is adjusted to neutral. The mixture is dialyzed and freeze-dried to obtain vinyl gelatin.

The reaction formula of the preparation method is as follows:

In the above-mentioned preparation process, the present invention preferably mixes gelatin and water, and then adjusts the pH value of the solution to 10.50 with a 3 mol/L sodium hydroxide aqueous solution; preferably, after allyl glycidyl ether is dropped into the mixture for reaction, the pH value is adjusted to neutral with a 3 mol/L hydrochloric acid solution; the present invention preferably has a mass ratio of gelatin to allyl glycidyl ether of 20:1.

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

Furthermore, the present invention preferably performs photocuring during the preparation of the aqueous humor drainage device by adding at least one of the photoinitiators diphenyl-(2,4,6-trimethylbenzoyl)phosphine oxide (TPO), 1-hydroxycyclohexyl phenyl ketone (184), 2-hydroxy-4'-(2-hydroxyethoxy)-2-methylpropiophenone (2959), ethyl 2,4,6-trimethylbenzoylphenylphosphonate (TPO-L), and phenylbis(2,4,6-trimethylbenzoyl)phosphine oxide (819); and preferably, the molar ratio of the photoinitiator to the thiol-ene material is (0.5-2.5):100.

In addition, the present invention further preferably has the surface of the aqueous humor drainage device chemically modified by methacryloylated dextran (DXM) so as to limit cell adhesion and diffusion by modifying the dextran on the surface of the aqueous humor drainage device, thereby reducing the risk of blockage of the aqueous humor drainage device 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 aqueous humor drainage device as described above, comprising the following process: mixing a thiol material, an olefin material, and a photoinitiator according to the formula, injecting the mixture into a microfluidic mold, and irradiating the mold with ultraviolet light to obtain an aqueous humor drainage device.

The preparation method of the aqueous humor drainage device provided by the present invention is prepared by a thiol-ene material with good compatibility through a photocuring method. Since the material does not contain a degradable group, the aqueous humor drainage device prepared with the material will not degrade during use while ensuring biocompatibility, thereby improving the stability of the aqueous humor drainage device structure and enabling it to function as a permanent implant; by adopting microfluidics and mold remodeling technology, the processing technology is optimized, the production efficiency is improved, and mass production is facilitated.

Furthermore, 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 into the methacryloylated dextran aqueous solution, shaking at 37° C., to obtain a surface-modified aqueous humor drainage device.

The mass fraction of the methacryloylated dextran aqueous solution in the present invention is preferably 15%; by modifying the surface of the aqueous humor drainage device with methacryloylated dextran, cell adhesion and diffusion can be restricted, thereby reducing the risk of blockage of the aqueous humor drainage device due to cell adhesion.

In order to make the above-mentioned objects, features and advantages of the present invention more obvious and easy to understand, specific embodiments of the present invention are described in detail below with reference to the accompanying drawings.

Unless otherwise specified, the vinyl gelatin in each embodiment and comparative example of the present invention is prepared according to the following method:

In a round-bottom flask (100 ml) equipped with a thermometer, a stirrer and a reflux condenser, 5.935 g of gelatin and 60 ml of water were added, and the pH value of the solution was adjusted to 10.50 with a 3 mol L ^-1 sodium hydroxide aqueous solution, and then 0.29675 g of allyl glycidyl ether was dropped. The reaction was allowed to react for 4 hours, and the pH of the reaction mixture was adjusted to neutral with a 3 mol L ^-1 hydrochloric acid aqueous solution. The mixture was dialyzed for 3 days and freeze-dried to obtain vinyl gelatin.

FIG1 and FIG2 are ¹ H NMR spectra of raw gelatin and vinyl gelatin, respectively. Comparing FIG1 with FIG2 , it can be seen that vinyl gelatin has new peaks of vinyl at δ=5.35ppm and 5.75ppm.

Unless otherwise specified, the maleic anhydride-modified mitomycin in each embodiment and comparative example of the present invention was prepared according to the following method:

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

FIG3 and FIG4 are the NMR spectra of the raw material MMC and maleic anhydride-modified mitomycin (MMC-MA) of the present invention, respectively. By comparing FIG3 and FIG4 , it can be seen that MMC-MA has new characteristic peaks after maleic anhydride ring opening at δ=5.65ppm, 5.83ppm, and 6.27ppm.

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

Example 1

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

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 were mixed and injected into a microfluidic mold. The mixture was irradiated with ultraviolet light at a wavelength of 355 nm for 30 seconds to obtain an aqueous humor drainage device. The aqueous humor drainage device was then added into a 15% mass fraction aqueous solution of methacryloylated dextran (DXM), and the mixture was shaken at 37°C for 7 days to obtain a surface-modified aqueous humor drainage device.

Example 2

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

0.5 mol of dithiothreitol, 0.5 mol of DT1, 0.99 mol of vinyl gelatin, 0.0099 mol of maleic anhydride-modified mitomycin MMC-MA, and 0.025 mol of initiator 184 were injected into a microfluidic mold and irradiated with ultraviolet light at a wavelength of 355 nm for 30 seconds to obtain an aqueous humor drainage device; the aqueous humor drainage device was then added into a 15% by mass aqueous solution of methacryloylated dextran (DXM), and the mixture was shaken at 37°C for 7 days to obtain a surface-modified aqueous humor drainage device.

Example 3

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

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

Comparative Example 1

This comparative example provides an aqueous humor drainage device, and its preparation method is as follows:

1.5 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 were mixed, injected into a microfluidic mold, and irradiated with ultraviolet light at a wavelength of 355 nm for 30 seconds to obtain an aqueous humor drainage device; then the aqueous humor drainage device was added into a 15% mass fraction of methacryloylated dextran (DXM) aqueous solution, and shaken at 37°C for 7 days to obtain a surface-modified aqueous humor drainage device.

Comparative Example 2

This comparative example provides an aqueous humor drainage device, and its preparation method is as follows:

0.5 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 were mixed and injected into a microfluidic mold. The mixture was irradiated with ultraviolet light of a wavelength of 355 nm for 30 seconds to obtain an aqueous humor drainage device. The aqueous humor drainage device was then added into a 15% by mass aqueous solution of methacryloylated dextran (DXM), and the mixture was shaken at 37°C for 7 days to obtain a surface-modified aqueous humor drainage device.

Comparative Example 3

This comparative example provides an aqueous humor drainage device, and its preparation method is as follows:

1 mol of dithiothreitol, 0.909 mol of maleic anhydride-modified mitomycin MMC-MA and 0.005 mol of initiator TPO were mixed and injected into a microfluidic mold. After irradiation with ultraviolet light at a wavelength of 355 nm for 30 seconds, the desired aqueous humor drainage device could not be obtained.

Comparative Example 4

This comparative example provides an aqueous humor drainage device, and its preparation method is as follows:

1 mol of dithiothreitol, 0.909 mol of vinyl gelatin and 0.005 mol of initiator TPO were mixed and injected into a microfluidic mold. The mixture was irradiated with ultraviolet light at a wavelength of 355 nm for 30 seconds to obtain an aqueous humor drainage device. The aqueous humor drainage device was then added into a 15% mass fraction of methacryloylated dextran (DXM) aqueous solution and shaken at 37°C for 7 days to obtain a surface-modified aqueous humor drainage device.

Comparative Example 5

This comparative example provides an aqueous humor drainage device, and its preparation method is as follows:

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 were mixed and injected into a microfluidic mold. The mixture was irradiated with ultraviolet light at a wavelength of 355 nm for 120 s to obtain an aqueous humor drainage device. The aqueous humor drainage device was then added into a 15% mass fraction of methacryloylated dextran (DXM) aqueous solution and shaken at 37°C for 7 days to obtain a surface-modified aqueous humor drainage device.

Comparative Example 6

This comparative example provides an aqueous humor drainage device, and its preparation method is as follows:

1 mol of dithiothreitol, 0.9 mol of gelatin, 0.009 mol of maleic anhydride-modified mitomycin MMC-MA and 0.005 mol of initiator TPO were mixed and injected into a microfluidic mold. The mixture was irradiated with ultraviolet light at a wavelength of 355 nm for 30 seconds to obtain an aqueous humor drainage device. The aqueous humor drainage device was then added into a 15% mass fraction of methacryloylated dextran (DXM) aqueous solution and shaken at 37°C for 7 days to obtain a surface-modified aqueous humor drainage device.

Comparative Example 7

This comparative example provides an aqueous humor drainage device, and its preparation method is as follows:

1 mol of dithiothreitol, 0.9 mol of vinyl gelatin, 0.009 mol of mitomycin MMC and 0.005 mol of initiator TPO were mixed, injected into a microfluidic mold, and irradiated with ultraviolet light at a wavelength of 355 nm for 60 seconds to obtain an aqueous humor drainage device; then the aqueous humor drainage device was added into a 15% mass fraction of methacryloylated dextran (DXM) aqueous solution, and shaken at 37°C for 7 days to obtain a surface-modified aqueous humor drainage device.

Comparative Example 8

This comparative example provides an aqueous humor drainage device, and its preparation method is as follows:

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 were mixed, injected into a microfluidic mold, and irradiated with ultraviolet light at a wavelength of 355 nm for 30 seconds to obtain an aqueous humor drainage device.

The performance of the aqueous humor drainage devices prepared in each embodiment and comparative example was tested according to the following method:

Cytostatic Effect Test:

The effect of cell inhibition was evaluated by cell response. Primary fibroblasts (10 cells/well) were cultured with DMEM containing 10% fetal bovine serum by mass. After the fibroblasts were precipitated, the aqueous humor drain was inserted into the migration test so that it was completely immersed in the medium. After 5 days of culture, the state of fibroblasts was detected by live/dead staining and CCK-8, and the live/dead ratio of fibroblasts (HTFs) at 5 days was calculated. The higher the activity of fibroblasts, the more severe the scarring.

Cell Adhesion Test:

3T3 mouse embryonic bromide cells were maintained in T-75 Falcon cell culture medium (DMEM) containing 10% fetal bovine serum (FBS) and 100 units/ml penicillin and 0.1 mg/ml streptomycin using sterile Dulbecco's modified Falcon medium (DMEM) with 10% fetal bovine serum (FBS) and 100 units/ml penicillin and 0.1 mg/ml streptomycin. Six samples of each cover (36 samples in total) were placed in 6-well tissue culture plates and irradiated under UV light for 10-15 minutes. Cells were seeded onto the coverslips at a density of approximately 11 000 cells/cm. The cells were then incubated at 37°C, 5% CO2 for 24 h, after which the medium was decanted and gently rinsed once with PBS. The number of adherent cells was defined as the number of viable cells per 100*field. The percentage of control adhesion was calculated by multiplying the ratio of the percentage of viable cells on the treated substrate to the percentage of viable cells on the untreated substrate by 100. The mean control adhesion rate was determined for each sample group, and statistical comparisons of viability assays were performed as described above.

Quality loss rate test:

Degradation stability testing is determined by measuring the weight change of samples after immersion in 1 mol sodium hydroxide at 37°C for 4 time points over 1 month. The samples consist of 10 mg mechanically cut cylinders with a diameter of 1.6 mm and a height of 1.2 mm. The dry mass of each sample is measured with a precision of 0.1 μg. 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. The mass loss is the mass inside the (polytetrafluoroethylene) block after the sample is placed on the polytetrafluoroethylene; placed in a vacuum oven at 120°C for 24 hours, and then the sample is removed and reweighed to determine the final mass lost. The mass loss is calculated as the change from the initial weight to the vacuum dried mass as a mass percentage. The data reported is the average 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 drainage devices prepared in various embodiments of the present invention have excellent structural stability, and are helpful in reducing scarring and limiting cell adhesion and diffusion.

Compared with Example 1, Comparative Example 1 increases the amount of thiol material added in the thiol-ene material. Although the prepared aqueous humor drainage device reduces cell adhesion and reduces the risk of aqueous humor drainage device blockage, its mass loss rate increases and the structural stability of the aqueous humor drainage device deteriorates.

Compared with Example 1, Comparative Example 2 reduces the amount of thiol material added in the thiol-ene material, the adhesion of cells in the prepared aqueous humor drainage device increases, the risk of clogging of the aqueous humor drainage device increases, and the mass loss rate also decreases slightly, and the structural stability deteriorates.

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

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

Compared with Example 1, Comparative Example 5 increases the amount of the first olefin material added in the olefin material, the molding difficulty increases, and the required molding time becomes longer; although the aqueous humor drainage device can be molded, the prepared aqueous humor drainage device has a lower live/dead ratio of HTFs fibroblasts at 5 days and a lower risk of scarring, but the mass loss rate increases and the structural stability deteriorates.

Compared with Example 1, in Comparative Example 6, gelatin was used instead of vinyl gelatin, but the aqueous humor drainage device could not be formed by cross-linking.

In Comparative Example 7 compared with Example 1, MMC is used instead of MMC-MA, which increases the difficulty of molding and prolongs the required molding time; the live/dead ratio of HTFs fibroblasts in the prepared aqueous humor drainage device increases after 5 days; MMC is not covalently bonded to the aqueous humor drainage device but filled in the aqueous humor drainage device in the form of a blend, which reduces the ability to inhibit scarring in the long term; at the same time, the mass loss rate increases and the stability of the structure deteriorates.

Compared with Example 1, in Comparative Example 8, the surface of the aqueous humor drainage device was not chemically modified by using methacryloyl dextran. The cell adhesion of the prepared aqueous humor drainage device was significantly increased, and the 5-day HTFs fibroblast live/dead ratio was also increased, and the risk of scarring was increased compared with Example 1.

Based on the above ideal embodiments of the present invention, the relevant staff can make various changes and modifications without departing from the technical concept of the present invention through the above description. The technical scope of the present invention is not limited to the contents of the specification, and its technical scope must be determined according to the scope of the claims.

Claims (10)

1. An aqueous humor drainage device is characterized by being in a tubular structure; the aqueous humor drainage device is prepared from a mercaptan-alkene material by a photocuring method; the mercaptan material in the mercaptan-alkene material is at least one selected from tetrahydrodicyclopentadiene dimethyl mercaptan, 1, 10-decanedithiol, tetra (ethyl mercaptan) silane, 1,3, 5-tri (propyl mercaptan) isocyanurate and dithiothreitol; the olefinic materials in the thiol-olefinic material include a first olefinic material and a second olefinic material; the first olefinic material is maleic anhydride modified mitomycin; the second material is selected from at least one of trimethylolpropane triallyl ether, pentaerythritol triallyl ether, 2,4, 6-tri (allyloxy) -1,3, 5-trihydrazine, 1,3, 5-triallyl-1, 3, 5-triazine-2, 4,6 (1H, 3H, 5H) -trione and vinyl gelatin.

2. The aqueous humor drainage device of claim 1, wherein the maleic anhydride modified mitomycin is prepared according to the following method:

Adding mitomycin, maleic anhydride and a solvent into a three-neck flask, stirring and reacting at 40 ℃, and precipitating a reaction product with ethanol to obtain maleic anhydride modified mitomycin.

3. The aqueous humor drainage device of claim 2, wherein the molar ratio of mitomycin to 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:

Mixing gelatin with water, regulating pH value to be alkaline, then dripping allyl glycidyl ether to react, regulating pH value to be neutral, sequentially dialyzing, and freeze-drying 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 of any one of claims 1 to 5, wherein the molar ratio of the first olefinic material to the second olefinic material is (0.1 to 1): 100.

7. The aqueous humor drainage device of claim 6, wherein the molar ratio of olefinic material to thiol material in the thiol-ene material is (0.9-0.99): 1.

8. The aqueous humor diverter of claim 7, wherein the surface of the aqueous humor diverter is further chemically modified by methacrylated dextran.

9. A method of preparing an aqueous humor drainage device according to any one of claims 1 to 8, comprising the steps of: according to the formula amount, mixing a mercaptan material, an alkene material and a photoinitiator, injecting the mixture into a microfluidic mould, and irradiating the mixture by ultraviolet light to obtain the aqueous humor drainage device.

10. The method for preparing an aqueous humor drainage device according to claim 9, further comprising the following steps: adding the aqueous humor drainage device into a methylacryloyl dextran aqueous solution, and oscillating at 37 ℃ to obtain the surface modified aqueous humor drainage device.