Photocurable material and aqueous humor drainage device and method of manufacturing the same

Abstract

The application provides a photocuring material and an aqueous humor drainage device and a preparation method thereof, and relates to the technical field of medical devices; the photocuring material is composed of an A component, a B component and a photoinitiator I; the A component comprises A1 raw materials and A2 raw materials; the A1 raw materials simultaneously contain an antimetabolite structure, an F element and a mercapto group; the A2 raw materials are mercapto group-containing compounds; the B component comprises B1 raw materials and B2 raw materials; the B1 raw materials are selected from at least one of triallyl isocyanurate, trimethylolpropane triacrylate, ethyl acrylate and 2-phenylethyl methacrylate; and the B2 raw materials are modified gelatin. The mercapto-ene material with good biocompatibility is adopted, the antimetabolite structure and the F element are combined, the postoperative scar formation of a surgical site can be effectively reduced, the photocuring material has good cell adsorption resistance, and the drainage efficiency is improved.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of medical devices, in particular to a light-cured material and an aqueous humor drainage device and a preparation method thereof. BACKGROUND

[0002] At present, most of the glaucoma diseases in the clinic can be treated by controlling intraocular pressure through drainage device implantation. Implanting the drainage device can achieve the effect of reducing intraocular pressure and realizing the control treatment of glaucoma.

[0003] There are mainly three ways for the aqueous humor drainage device to drain aqueous humor: subconjunctival drainage, Schlemm's tube drainage and choroid-sclera pathway drainage. The key to the success of subconjunctival drainage surgery is to form a functional filtering bleb. This type of surgery will also have some complications, such as filtering bleb scarring and filtering bleb thinning, which will result in glaucoma surgery failure. The physiological pathway of aqueous humor outflow is mainly the Schlemm's tube. The principle is to open the physiological drainage channel from the anterior chamber to the Schlemm's tube to achieve the purpose of aqueous humor drainage. At present, hospitals have adopted this method for surgery, but this drainage surgery is not suitable for pigmentary glaucoma with pigment deposition of the trabecular meshwork and open-angle glaucoma with high sub-scleral venous pressure. The choroid-sclera pathway drainage is a new way of aqueous humor drainage, which avoids some complications that may be caused by functional filtering bleb dependent surgery, and can be used for pigmentary glaucoma with pigment deposition of the trabecular meshwork and open-angle glaucoma with high sub-scleral venous pressure which cannot be treated by Schlemm's tube drainage device. However, there are few products of the choroid-sclera pathway drainage at present, and the minimally invasive implant products of the choroid-sclera pathway drainage are even rarer.

[0004] The aqueous humor drainage device for treating glaucoma is a tubular structure which can be minimally invasive implanted, with an outer diameter of only 100-900 μm and an inner diameter of 10-100 μm. It is usually very thin and soft and elastic, and can guide the aqueous humor out of the eye to reduce the intraocular pressure.

[0005] The development of the aqueous humor drainage device has great difficulty. On the one hand, the diameter of the glaucoma minimally invasive drainage tube is extremely thin, and the preparation process has high requirements. The material of the tube body should have appropriate physical and chemical properties to have the possibility of preparing the drainage tube. On the other hand, the raw material should be safe, non-toxic and non-allergic. In addition, the aqueous humor drainage device should have no foreign body sensation after implantation, good compliance with the ocular tissue, and good drainage and pressure reduction effect.

[0006] The existing drainage tube is usually prepared by photocuring of photocuring material; the photocuring material can meet the requirements of good compliance of the drainage tube with the ocular tissue, safe use, non-toxicity and the like, but still has the problem of low drainage efficiency, which limits the application of the drainage tube. SUMMARY

[0007] The technical problem solved by the present application is that, in order to solve the problem of low drainage efficiency of the aqueous humor drainage device in the prior art, the present application provides a photocuring material, which introduces F element and anti-metabolic structure at the same time, adjusts hydrophilicity while reducing postoperative scarring of the surgical site, thereby helping to improve the drainage efficiency of the aqueous humor drainage device, and solving the problem of low drainage efficiency of the aqueous humor drainage device in the prior art.

[0008] The technical solution adopted by the present application to solve the technical problem is:

[0009] A photocuring material, which is composed of A component, B component and photoinitiator I;

[0010] The A component includes A1 raw material and A2 raw material;

[0011] The A1 raw material contains anti-metabolic structure, F element and mercapto group at the same time;

[0012] The A2 raw material is a mercapto-containing compound;

[0013] The B component includes B1 raw material and B2 raw material;

[0014] The B1 raw material is at least one selected from triallyl isocyanurate, trimethylolpropane triacrylate, ethyl acrylate and 2-phenylethyl methacrylate;

[0015] The B2 raw material is modified gelatin.

[0016] Optionally, the anti-metabolic structure is thymine structure.

[0017] Optionally, the A1 raw material is prepared by the following method:

[0018] S1: mixing trimethylolpropane tris(3-mercaptopropionate), photoinitiator II and dichloromethane A to obtain a mixed solution I; dissolving an unsaturated alcohol in dichloromethane B to obtain a mixed solution II; under UV lamp irradiation, the mixed solution II is added dropwise into the mixed solution I for reaction; after the reaction is completed, vacuum distillation is performed to obtain an intermediate product I;

[0019] S2: mixing the intermediate product I, triethylamine, dichloromethane C to obtain a mixed solution III; mixing perfluoroalkyl acid chloride, dichloromethane D under ice bath condition to obtain a mixed solution IV; adding the mixed solution IV dropwise into the mixed solution III, stirring, standing, filtering, taking the filtrate, washing; standing, separating, taking the organic phase, drying, filtering, taking the filtrate, reducing pressure distillation, vacuum drying to constant weight to obtain the intermediate product II;

[0020] S3: mixing 5-formyluracil, allylamine, anhydrous magnesium sulfate, dichloromethane E under inert gas protection condition, stirring at 20℃, filtering, taking the filtrate, reducing pressure distillation, vacuum drying at room temperature to obtain the intermediate product III;

[0021] S4: mixing the intermediate product II, photoinitiator III, dichloromethane F to obtain a mixed solution V; dissolving the intermediate product III in dichloromethane G to obtain a mixed solution VI; adding the mixed solution VI dropwise into the mixed solution V under UV lamp irradiation to carry out reaction; after the reaction is completed, reducing pressure distillation to obtain the A1 raw material.

[0022] Optionally, the unsaturated alcohol is at least one selected from 9-decen-1-ol, undecenol, 5-hexenyl-1-ol.

[0023] Optionally, the perfluoroalkyl acid chloride is at least one selected from heptafluorobutyryl chloride, perfluorooctanoyl chloride.

[0024] Optionally, the molar ratio of the trimethylolpropane tris(3-mercaptopropionate) to the unsaturated alcohol in step S1 is 1: (0.8-1.2); the amount of the photoinitiator II in step S1 is 1wt% of the total mass of the reactants in step S1.

[0025] Optionally, the molar ratio of the intermediate product I, the triethylamine, the perfluoroalkyl acid chloride in step S2 is 1: (0.8-1.2): (0.8-1.2).

[0026] Optionally, the molar ratio of the 5-formyluracil, the allylamine, the anhydrous magnesium sulfate in step S3 is 1: (0.8-1.2): (0.8-1.2).

[0027] Optionally, the molar ratio of the intermediate product II, the intermediate product III in step S4 is 1:1; the amount of the photoinitiator III in step S4 is 1wt% of the total mass of the reactants in step S4.

[0028] Optionally, the A2 raw material is at least one selected from 3-mercapto-β,4-dimethylcyclohexane ethanethiol, bicyclo[2.2.1]heptane-2,3-dithiol, ethylene glycol bis(3-mercaptopropionate), trimethylolpropane tris(3-mercaptopropionate).

[0029] Optionally, the molar ratio of the A1 raw material to the A2 raw material in the A component is (0.01-0.05):(0.95-0.99).

[0030] Optionally, the mass ratio of the B1 raw material to the B2 raw material in the B component is 1:4.

[0031] Optionally, the ratio of the A component to the B component is 1:(0.95-0.99) in terms of the molar ratio of mercapto group to carbon-carbon double bond.

[0032] Optionally, the amount of the photoinitiator I is 0.5-1.5wt% of the total mass of the reactants.

[0033] Another object of the present application is to provide an aqueous humor drainage device prepared by a photocuring method from the photocuring material as described above.

[0034] Still another object of the present application is to provide a preparation method of the aqueous humor drainage device as described above, comprising the steps of: injecting the photocuring material into a microfluidic mold, irradiating by ultraviolet light, and oscillating in 37℃ physiological saline after curing to obtain the aqueous humor drainage device.

[0035] The present application has the following beneficial effects:

[0036] The photocuring material provided by the present application uses a mercapto-alkene material with good biocompatibility, and can be used to prepare an aqueous humor drainage device at room temperature or low temperature through a photocuring technology, thereby avoiding damage to the material caused by thermal stress in a thermal curing process; the introduced anti-metabolic structure combined with F element can effectively reduce the scarring of the surgical site after surgery, so that the aqueous humor drainage device has good anti-cell adsorption property and improves the drainage efficiency; and the introduction of sulfur-containing materials and gelatin into the raw materials helps to make the aqueous humor drainage device have good biocompatibility and mechanical properties. BRIEF DESCRIPTION OF DRAWINGS

[0037] The present application will be further described below in combination with the drawings and examples.

[0038] Figure 1 is the infrared spectrum of the intermediate product I in Example 1 of the present application;

[0039] Figure 2 is the infrared spectrum of the intermediate product II in Example 1 of the present application;

[0040] Figure 3is the infrared spectrum of the intermediate product III in Example 1 of the present application.

[0041] Figure 4 is the infrared spectrum of the A1 raw material in Example 1 of the present application. DETAILED DESCRIPTION

[0042] The present application will now be further described in detail. The examples described below are exemplary and are intended to serve to explain the present application and cannot be understood as limiting the present application, all other examples obtained by a person of ordinary skill in the art based on the examples of the present application without making creative efforts fall within the scope of protection of the present application.

[0043] In order to solve the problem of low drainage efficiency of aqueous humor drainage device in the prior art, the present application provides a photocurable material, which is composed of A component, B component and photoinitiator I; wherein the A component comprises A1 raw material and A2 raw material; the A1 raw material simultaneously contains anti-metabolic structure, F element and mercapto group; the A2 raw material is a mercapto-containing compound; the B component comprises B1 raw material and B2 raw material; the B1 raw material is selected from at least one of triallyl isocyanurate, trimethylolpropane triacrylate, ethyl acrylate and 2-phenylethyl methacrylate; and the B2 raw material is modified gelatin.

[0044] In order to ensure the smooth forming of the aqueous humor drainage device, the present application preferably prepares the modified gelatin according to the following method:

[0045] The gelatin is mixed with water, the pH value of the solution is adjusted to alkaline by alkali solution, then allyl glycidyl ether is added dropwise, the pH value of the reaction mixture is adjusted to neutral by acidic solution, dialysis is performed for 3 days, freeze-drying is performed, and the B2 raw material, i.e. the modified gelatin, is obtained; wherein the mass ratio of the gelatin to the allyl glycidyl ether is 20:1.

[0046] The A component of the photocurable material contains mercapto group, and the B component contains carbon-carbon double bond, so the present application can prepare the aqueous humor drainage device by the photocuring method from the mercapto-alkene material.

[0047] Since the aqueous humor drainage device needs to be implanted in the body for a long time during use, postoperative fibroblast proliferation will block the aqueous humor drainage device during use, and cells in tissue fluid will also adhere to the aqueous humor drainage device, eventually leading to poor filtering effect of the aqueous humor drainage device and failure; based on this, the application simultaneously introduces an anti-metabolic structure and F element into the system through A1 raw material, wherein the anti-metabolic structure can prevent cell division, has excellent anti-metabolic effect, can reduce postoperative scarring of the surgical site, and improve the drainage filtering effect; the F element has low atomic surface energy, can make A1 raw material enriched at the material interface, and in combination with the anti-metabolic structure, further improves the anti-metabolic effect; at the same time, the interface is adjusted by a large number of F elements to make the interface hydrophilic, so as to have good anti-cell adsorption, which helps to further improve the drainage efficiency; in addition, since the A1 raw material contains a mercapto structure, it can react with the carbon-carbon double bond in the B component, so that the A1 raw material can be fixed to the material system, reducing the existence of free small molecules in the system, and avoiding the harm to the body caused by the existence of small molecules.

[0048] The photocuring material provided by the application can be used to prepare the aqueous humor drainage device at room temperature or low temperature through the photocuring technology, so as to avoid the damage of thermal stress in the heat curing process; the anti-metabolic structure and the F element are combined to effectively reduce the postoperative scarring of the surgical site, so as to have good anti-cell adsorption and improve the drainage efficiency; and the raw material introduces the sulfur-containing material and gelatin, which helps to make the aqueous humor drainage device have good biocompatibility and mechanical properties.

[0049] In order to ensure the anti-metabolic effect of the aqueous humor drainage device, the application preferably uses thymine structure as the anti-metabolic structure, which is used to prevent cell division, reduce postoperative scarring of the surgical site, and improve the drainage filtering effect.

[0050] Specifically, the A1 raw material is prepared according to the following method:

[0051] S1: mix trimethylolpropane tris(3-mercaptopropionate), a photoinitiator II, and dichloromethane A to obtain a mixed solution I; dissolve an unsaturated alcohol in dichloromethane B to obtain a mixed solution II; under the condition of UV lamp irradiation, drop the mixed solution II into the mixed solution I to carry out a reaction; after the reaction is completed, perform vacuum distillation to obtain an intermediate product I;

[0052] S2: mix the intermediate product I, triethylamine, and dichloromethane C to obtain a mixed solution III; mix perfluoroalkyl acid chloride and dichloromethane D under ice bath conditions to obtain a mixed solution IV; drop the mixed solution IV into the mixed solution III, stir, and after the reaction, stand, filter, take the filtrate, wash; stand, separate, take the organic phase, dry, filter, take the filtrate, perform vacuum distillation, and vacuum dry to constant weight to obtain an intermediate product II;

[0053] S3: mixing 5-formyluracil, allylamine, anhydrous magnesium sulfate, dichloromethane E under inert gas protection, stirring at 20 DEG C, filtering, taking the filtrate, distilling under reduced pressure, and vacuum drying at room temperature to obtain intermediate product III;

[0054] S4: mixing intermediate product II, photoinitiator III, dichloromethane F to obtain mixed solution V; dissolving intermediate product III in dichloromethane G to obtain mixed solution VI; adding mixed solution VI dropwise into mixed solution V under UV lamp irradiation to perform reaction; after the reaction is completed, distilling under reduced pressure to obtain target product IV, i.e. A1 raw material.

[0055] The unsaturated alcohol is at least one selected from 9-decen-1-ol, undecenol, and 5-hexenyl-1-ol; and the perfluoroalkyl acyl chloride is at least one selected from heptafluorobutyryl chloride and perfluorooctanoyl chloride.

[0056] It should be noted that the photoinitiator I, the photoinitiator II, and the photoinitiator III in the present application can be the same or different; preferably, the photoinitiator I, the photoinitiator II, and the photoinitiator III are at least one selected from photoinitiator 2959, photoinitiator TPO-L, and photoinitiator 184.

[0057] The dichloromethane A, the dichloromethane B, the dichloromethane C, the dichloromethane D, the dichloromethane E, the dichloromethane F, and the dichloromethane G in the present application are only marked for distinguishing during the drafting process, and do not represent differences in performance or components.

[0058] In order to balance the drainage efficiency and mechanical properties of the aqueous humor drainage device, preferably, the molar amount ratio of trimethylolpropane tris(3-mercaptopropionate) to the unsaturated alcohol in step S1 is 1:(0.8-1.2); the amount of the photoinitiator II in step S1 is 1wt% of the total mass of the reactants in step S1; preferably, the molar amount ratio of intermediate product I, triethylamine, and perfluoroalkyl acyl chloride in step S2 is 1:(0.8-1.2):(0.8-1.2); preferably, the molar amount ratio of 5-formyluracil, allylamine, and anhydrous magnesium sulfate in step S3 is 1:(0.8-1.2):(0.8-1.2); preferably, the molar amount ratio of intermediate product II to intermediate product III in step S4 is 1:1; and the amount of the photoinitiator III in step S4 is 1wt% of the total mass of the reactants in step S4.

[0059] The preparation process of the A1 raw material is as follows:

[0060] .

[0061] wherein R is selected from at least one of (CH2)4, (CH2)8, (CH2)9; n is selected from at least one of 2, 6.

[0062] Preferably, the A2 raw material is selected from at least one of 3-mercapto-β,4-dimethylcyclohexane ethanethiol, bicyclo[2.2.1]heptane-2,3-dithiol, ethylene glycol bis(3-mercaptopropionate), trimethylolpropane tris(3-mercaptopropionate).

[0063] To balance the drainage efficiency and mechanical properties of the aqueous humor drainage device, the molar ratio of the A1 raw material to the A2 raw material in the A component is preferably (0.01-0.05):(0.95-0.99); and the mass ratio of the B1 raw material to the B2 raw material in the B component is preferably 1:4.

[0064] Preferably, the amount ratio of the A component to the B component in the photocuring material is 1:(0.95-0.99) in terms of the molar ratio of mercapto group to carbon-carbon double bond; and the amount of the photoinitiator I is 0.5-1.5wt% of the total mass of the reactants, i.e. the amount of the photoinitiator I is 0.5-1.5wt% of the total mass of the A component and the B component.

[0065] Another object of the present application is to provide an aqueous humor drainage device prepared by a photocuring method from the photocuring material as described above.

[0066] The aqueous humor drainage device provided by the present application is prepared by the photocuring technology at room temperature or low temperature, so that the damage of the material caused by thermal stress in the heat curing process can be avoided; the introduced anti-metabolic structure and F element can effectively reduce the scarring of the surgical site after surgery, so that the aqueous humor drainage device has good anti-cell adsorption property and improved drainage efficiency; and the introduction of the sulfur-containing material and gelatin into the raw material helps to improve the biocompatibility and mechanical properties of the aqueous humor drainage device.

[0067] Still another object of the present application is to provide a preparation method of the aqueous humor drainage device as described above, which comprises the following steps: injecting the photocuring material into a microfluidic mold, irradiating by ultraviolet light, and then oscillating in 37℃ physiological saline to obtain the aqueous humor drainage device.

[0068] The preparation method of the aqueous humor drainage device provided by the present application is prepared by the photocuring technology at room temperature or low temperature, so that the damage of the material caused by thermal stress in the heat curing process can be avoided; the introduced anti-metabolic structure and F element can effectively reduce the scarring of the surgical site after surgery, so that the aqueous humor drainage device has good anti-cell adsorption property and improved drainage efficiency; and the introduction of the sulfur-containing material and gelatin into the raw material helps to improve the biocompatibility and mechanical properties of the aqueous humor drainage device.

[0069] In order to make the above objectives, features and advantages of the present application more obvious and easy to understand, the specific embodiments of the present application are described in detail below.

[0070] In the absence of special instructions, the modified gelatin in each embodiment of the present application and the comparative examples is prepared according to the following method:

[0071] 5 g of gelatin is mixed with 60 mL of water, the pH value of the solution is adjusted to 10.5 with a 3 mol / L sodium hydroxide aqueous solution, then 0.25 g of allyl glycidyl ether is added dropwise and reacted for 4 h, then the pH of the reaction mixture is adjusted to neutral with a 3 mol / L hydrochloric acid aqueous solution, dialyzed for 3 days, and freeze-dried to obtain the modified gelatin, i.e., the B2 raw material.

[0072] In the following examples, the content of carbon-carbon double bonds in the raw material is determined by iodometric titration.

[0073] Example 1

[0074] The present embodiment provides a preparation method of an aqueous humor drainage device, comprising the following steps:

[0075] The A component, the B component and the photoinitiator 2959 are mixed, injected into a microfluidic mold, irradiated with ultraviolet light of a wavelength of 355 nm for 30 s, and then placed in a 37℃ physiological saline solution for oscillation for 7 d to obtain the aqueous humor drainage device.

[0076] The A component includes an A1 raw material and an A2 raw material; the amount ratio of the A1 raw material to the A2 raw material is 0.02 mol:0.98 mol;

[0077] The A2 raw material is a mixture of 3-mercapto-β,4-dimethylcyclohexane ethanethiol and ethylene glycol bis(3-mercaptopropionate) in a molar ratio of 0.5:0.5.

[0078] The B component includes a B1 raw material and a B2 raw material; the amount ratio of the B1 raw material to the B2 raw material is 2 g:8 g;

[0079] The B1 raw material is a mixture of triallyl isocyanurate and ethyl acrylate in a mass ratio of 0.6:1.4.

[0080] The amount ratio of the A component to the B component is 1:0.99 in terms of the molar ratio of mercapto groups to carbon-carbon double bonds; and the amount of the photoinitiator 2959 is 1.5 wt% of the total mass of the reactants.

[0081] The preparation method of the A1 raw material is as follows:

[0082] S1: Add trimethylolpropane tris(3-mercaptopropionate), photoinitiator TPO-L, and dichloromethane A to a flask. Dissolve 9-decen-1-ol in dichloromethane B and place the solution in a constant-pressure dropping funnel. Stir magnetically and add the solution dropwise at a uniform rate while placing the flask under a UV lamp with a wavelength of 355 nm and a light intensity of 400 mJ / cm². 2 Irradiate for 5 minutes; after the reaction is complete, remove the reaction apparatus and distill under reduced pressure to obtain intermediate product I;

[0083] The ratio of trimethylolpropane tris(3-mercaptopropionate) to 9-decen-1-ol is 1 mol: 1 mol;

[0084] The ratio of trimethylolpropane tris(3-mercaptopropionate) to dichloromethane A is 1 mol: 1200 mL;

[0085] The ratio of 9-decen-1-ol to dichloromethane B is 1 mol: 450 mL;

[0086] The amount of photoinitiator TPO-L used is 1 wt% of the total mass of the reactants in step S1;

[0087] See Figure 1 As shown, the infrared data for intermediate product I is as follows: 3443 cm⁻¹ -1 -OH is present; 2550cm -1 -SH exists and weakens; 1733 cm -1 -C=O exists; 1631cm -1 -C=C- does not exist.

[0088] S2: Add intermediate product I, triethylamine, and dichloromethane C to a flask and stir. Place perfluorooctanoyl chloride and dichloromethane D in a constant pressure dropping funnel. Place the flask in an ice bath, stir magnetically, and add the flask dropwise at a uniform rate. After the addition is complete, continue stirring for 8 hours. Stop stirring, let stand, filter, take the filtrate, wash 3 times with 20wt% dilute hydrochloric acid solution, wash 3 times with saturated sodium bicarbonate aqueous solution, and then wash 3 times with deionized water A. Let stand, separate the liquid and liquid, take the organic phase, dry it with anhydrous sodium sulfate, filter, take the filtrate, distill under reduced pressure, and dry it under vacuum at 50°C to constant weight to obtain intermediate product II.

[0089] The ratio of intermediate product I, triethylamine, and perfluorooctanoyl chloride is 1 mol: 1 mol: 1 mol;

[0090] The ratio of intermediate product I to dichloromethane C was 1 mol: 1660 mL;

[0091] The ratio of perfluorooctanoyl chloride to dichloromethane D is 1 mol: 1300 mL;

[0092] See Figure 2The infrared data of the intermediate product II is shown as follows: 3443 cm -1 : -OH disappears; 2550 cm -1 : -SH exists; 1733 cm -1 : -C=O exists; 1350 cm -1 : -C-F exists.

[0093] S3: N2 protection, 5-formyluracil, allylamine, anhydrous magnesium sulfate, dichloromethane E are added into a three-necked flask, stirred at 20°C for 20h, then filtered, the filtrate is distilled under reduced pressure, and vacuum dried at room temperature to obtain the intermediate product III;

[0094] The amount ratio of formyluracil, allylamine, and anhydrous magnesium sulfate is 1 mol: 1 mol: 1 mol;

[0095] The amount ratio of 5-formyluracil and dichloromethane E is 1 mol: 420 mL;

[0096] Referring to Figure 3 The infrared data of the intermediate product III is shown as follows: 1555 cm -1 : -NH- (amide) exists; 1676 cm -1 : -C=O (ketone group in the pyrimidine ring) exists; 1612 cm -1 : -C=C- (pyrimidine) exists; 1720 cm -1 , 2870 cm -1 , 2720 cm -1 : H-C=O (aldehyde group) disappears; 1634 cm -1 : -C=C- exists.

[0097] S4: the intermediate product II, the photoinitiator TPO-L, dichloromethane F are added into a flask, the intermediate product III is dissolved in dichloromethane G and placed in a constant pressure dropping funnel, magnetically stirred, and dropped at a uniform speed while placed under a UV lamp with a wavelength of 355 nm and an intensity of 400 mJ / cm 2 for 5 min; after the reaction is completed, the reaction device is removed, and distilled under reduced pressure to obtain the target product IV, i.e., the A1 raw material;

[0098] The amount ratio of the intermediate product II and the intermediate product III is 1 mol: 1 mol;

[0099] The amount ratio of the intermediate product II and dichloromethane F is 1 mol: 3000 mL;

[0100] The amount ratio of the intermediate product III and dichloromethane G is 1 mol: 600 mL;

[0101] The amount of photoinitiator TPO-L is 1wt% of the total mass of the reactants in step S4.

[0102] Referring to Figure 4 The infrared data of the A1 raw material is as follows: 2550 cm -1 : -SH exists and is weakened; 1733 cm -1 : -C=O (ester group) exists; 1350 cm -1 : -C-F exists; 1555 cm -1 : -NH- (amide) exists; 1676 cm -1 : -C=O (ketone group in the pyrimidine ring) exists; 1612 cm -1 : -C=C- (pyrimidine) exists; 1634 cm -1 : -C=C- disappears.

[0103] Example 2

[0104] The present embodiment provides a preparation method of an aqueous humor drainage device, comprising the following steps:

[0105] The A component, the B component, and the photoinitiator TPO-L are mixed and injected into a microfluidic mold, irradiated with ultraviolet light of a wavelength of 355 nm for 30 s, and then placed in a 37℃ physiological saline solution for oscillation for 7 d to obtain the aqueous humor drainage device for glaucoma.

[0106] The A component includes an A1 raw material and an A2 raw material; the amount ratio of the A1 raw material to the A2 raw material is 0.01 mol:0.99 mol;

[0107] The A2 raw material is a mixture of bicyclo[2.2.1]heptane-2,3-dithiol and ethylene glycol bis(3-mercaptopropionate) in a molar ratio of 0.3:0.7.

[0108] The B component includes a B1 raw material and a B2 raw material; the amount ratio of the B1 raw material to the B2 raw material is 2g:8g;

[0109] The B1 raw material is a mixture of trimethylolpropane triacrylate, ethyl acrylate, and 2-phenylethyl methacrylate in a mass ratio of 0.8:0.8:0.4.

[0110] The amount ratio of the A component to the B component is 1:0.97 in terms of the molar ratio of mercapto groups to carbon-carbon double bonds; and the amount of the photoinitiator TPO-L is 0.5wt% of the total mass of the reactants.

[0111] The preparation method of the A1 raw material is as follows:

[0112] S1: Trimethylolpropane tris(3-mercaptopropionate), photoinitiator 2959, dichloromethane A were added into a flask, undecylenic alcohol was dissolved in dichloromethane B and placed in a constant pressure dropping funnel, magnetic stirring, uniform speed drop was added at the same time under UV lamp, wavelength was 355 nm, light intensity was 400 mJ / cm 2 , irradiation was performed for 10 min; after the reaction was completed, the reaction device was removed, and vacuum distillation was performed to obtain intermediate product I;

[0113] The amount ratio of trimethylolpropane tris(3-mercaptopropionate) to undecylenic alcohol was 1 mol: 1 mol;

[0114] The amount ratio of trimethylolpropane tris(3-mercaptopropionate) to dichloromethane A was 1 mol: 1200 mL;

[0115] The amount ratio of undecylenic alcohol to dichloromethane B was 1 mol: 510 mL;

[0116] The amount of photoinitiator 2959 was 1 wt% of the total mass of the reactants in step S1.

[0117] S2: Intermediate product I, triethylamine, dichloromethane C were added into a flask, stirring, perfluorooctanoyl chloride, dichloromethane D was placed in a constant pressure dropping funnel, ice bath, magnetic stirring, uniform speed drop was added, after the drop was completed, stirring was continued for 12 h; stirring was stopped, and standing, filtration, the filtrate was taken, 20 wt% dilute hydrochloric acid solution was added and washed for 3 times, saturated sodium bicarbonate aqueous solution was added and washed for 3 times, and deionized water A was added and washed for 3 times, standing, liquid separation, the organic phase was taken, anhydrous sodium sulfate was added and dried, filtration, the filtrate was taken, vacuum distillation, vacuum drying at 50℃ until constant weight, to obtain intermediate product II;

[0118] The amount ratio of intermediate product I, triethylamine, perfluorooctanoyl chloride was 1 mol: 1 mol: 1 mol;

[0119] The amount ratio of intermediate product I to dichloromethane C was 1 mol: 1700 mL;

[0120] The amount ratio of perfluorooctanoyl chloride to dichloromethane D was 1 mol: 1300 mL.

[0121] S3: N2 protection, 5-formyluracil, allylamine, anhydrous magnesium sulfate, dichloromethane E were added into a three-necked flask, stirring at 20℃ for 20 h, then filtration, the filtrate was taken, vacuum distillation, vacuum drying at room temperature, to obtain intermediate product III;

[0122] The amount ratio of 5-formyluracil, allylamine, anhydrous magnesium sulfate was 1 mol: 1 mol: 1 mol;

[0123] The amount ratio of 5-formyluracil to dichloromethane E was 1 mol: 420 mL.

[0124] S4: intermediate product II, photoinitiator 2959, dichloromethane F are added into a flask, intermediate product III is dissolved in dichloromethane G and placed in a constant pressure dropping funnel, magnetic stirring, uniform speed dropping is added at the same time, placed under UV lamp, wavelength is 355 nm, light intensity is 400 mJ / cm 2 , irradiation is performed for 10 min; after the reaction is completed, the reaction device is removed, and vacuum distillation is performed to obtain target product IV;

[0125] The amount ratio of intermediate product II to intermediate product III is 1 mol: 1 mol.

[0126] The amount ratio of intermediate product II to dichloromethane F is 1 mol: 3000 mL.

[0127] The amount ratio of intermediate product III to dichloromethane G is 1 mol: 600 mL.

[0128] The amount of photoinitiator 2959 is 1 wt% of the total mass of the reactants in step S4.

[0129] Example 3

[0130] The present embodiment provides a preparation method of an aqueous humor drainage device, comprising the following steps:

[0131] The A component, the B component and the photoinitiator 184 are mixed, injected into a microfluidic mold, irradiated by ultraviolet light with a wavelength of 355 nm for 30 s, and then placed in 37℃ physiological saline for oscillation for 7 d to obtain the aqueous humor drainage device for glaucoma.

[0132] The A component comprises an A1 raw material and an A2 raw material; the amount ratio of the A1 raw material to the A2 raw material is 0.03 mol: 0.97 mol.

[0133] The A2 raw material is a mixture of ethylene glycol bis(3-mercaptopropionate) and trimethylolpropane tris(3-mercaptopropionate) in a molar ratio of 0.6:0.4.

[0134] The B component comprises a B1 raw material and a B2 raw material; the amount ratio of the B1 raw material to the B2 raw material is 2 g: 8 g.

[0135] The B1 raw material is a mixture of triallyl isocyanurate, ethyl acrylate and 2-phenylethyl methacrylate in a mass ratio of 0.4:0.8:0.8.

[0136] The amount ratio of the A component to the B component is 1:0.97 in terms of the molar ratio of mercapto group to carbon-carbon double bond; the amount of the photoinitiator 184 is 1 wt% of the total mass of the reactants.

[0137] The preparation method of the A1 raw material is as follows:

[0138] S1: Trimethylolpropane tris(3-mercaptopropionate), photoinitiator 184, dichloromethane A were added into a flask, 5-hexenyl-1-ol was dissolved in dichloromethane B and placed in a constant pressure dropping funnel, magnetic stirring, uniform speed drop was added at the same time under UV lamp, wavelength was 355 nm, light intensity was 400 mJ / cm 2 , irradiation was performed for 8 min; after the reaction was completed, the reaction device was removed, and vacuum distillation was performed to obtain an intermediate product I;

[0139] The amount ratio of trimethylolpropane tris(3-mercaptopropionate) to 5-hexenyl-1-ol was 1 mol: 1 mol;

[0140] The amount ratio of trimethylolpropane tris(3-mercaptopropionate) to dichloromethane A was 1 mol: 1200 mL;

[0141] The amount ratio of 5-hexenyl-1-ol to dichloromethane B was 1 mol: 300 mL;

[0142] The amount of photoinitiator 184 was 1 wt% of the total mass of the reactants in step S1.

[0143] S2: The intermediate product I, triethylamine, dichloromethane C were added into a flask, stirring, perfluorooctyl chloride, dichloromethane D was placed in a constant pressure dropping funnel, ice bath, magnetic stirring, uniform speed drop was added, after the drop was completed, stirring was continued for 10 h; stirring was stopped, and standing, filtration, the filtrate was taken, 20 wt% dilute hydrochloric acid solution was added and washed for 3 times, saturated sodium bicarbonate aqueous solution was added and washed for 3 times, and deionized water A was added and washed for 3 times, standing, liquid separation, the organic phase was taken, anhydrous sodium sulfate was added and dried, filtration, the filtrate was taken, vacuum distillation, vacuum drying at 50°C until constant weight, to obtain an intermediate product II;

[0144] The amount ratio of the intermediate product I, triethylamine, perfluorooctyl chloride was 1 mol: 1 mol: 1 mol;

[0145] The amount ratio of the intermediate product I to dichloromethane C was 1 mol: 1500 mL;

[0146] The amount ratio of perfluorooctyl chloride to dichloromethane D was 1 mol: 1300 mL.

[0147] S3: N2 protection, 5-formyluracil, allylamine, anhydrous magnesium sulfate, dichloromethane E were added into a three-necked flask, stirring at 20°C for 20 h, then filtration, the filtrate was taken, vacuum distillation, vacuum drying at room temperature, to obtain an intermediate product III;

[0148] The amount ratio of 5-formyluracil, allylamine, anhydrous magnesium sulfate was 1 mol: 1 mol: 1 mol;

[0149] 5-formyluracil and dichloromethane E are used in a ratio of 1 mol: 420 mL.

[0150] S4: Intermediate product II, photoinitiator 184, dichloromethane F are added to a flask, intermediate product III is dissolved in dichloromethane G and placed in a constant pressure dropping funnel, magnetic stirring, uniform speed drop is added at the same time under UV lamp, wavelength is 355 nm, light intensity is 400 mJ / cm 2 , irradiation for 8 min; after the reaction is completed, remove the reaction device, reduce pressure distillation, to obtain the target product IV, i.e. A1 raw material;

[0151] The amount of intermediate product II and intermediate product III is 1 mol: 1 mol.

[0152] The amount of intermediate product II and dichloromethane F is 1 mol: 2800 mL.

[0153] The amount of intermediate product III and dichloromethane G is 1 mol: 600 mL.

[0154] The amount of photoinitiator 184 is 1wt% of the total mass of the reactants in step S4.

[0155] Example 4

[0156] The present embodiment provides a preparation method of aqueous humor drainage device, comprising the following steps:

[0157] A component, B component and photoinitiator 2959 are mixed and injected into a microfluidic mold, and then irradiated by ultraviolet light with a wavelength of 355 nm for 30 s. After curing, the glaucoma aqueous humor drainage device is obtained by oscillating in 37℃ physiological saline for 7 days.

[0158] The A component includes A1 raw material and A2 raw material; the amount of A1 raw material and A2 raw material is 0.03 mol: 0.97 mol.

[0159] The A2 raw material is ethylene glycol bis(3-mercaptopropionate).

[0160] The B component includes B1 raw material and B2 raw material; the amount of B1 raw material and B2 raw material is 2g: 8g.

[0161] The B1 raw material is a mixture of trimethylolpropane triacrylate, ethyl acrylate and 2-phenylethyl methacrylate in a mass ratio of 0.3:0.8:0.9.

[0162] The amount of A component and B component is 1:0.97 in terms of the molar ratio of mercapto group to carbon-carbon double bond; the amount of photoinitiator 2959 is 1wt% of the total mass of the reactants.

[0163] The preparation method of the above A1 raw material is as follows:

[0164] S1: Trimethylolpropane tris(3-mercaptopropionate), photoinitiator 2959, dichloromethane A are added to a flask, 9-decen-1-ol is dissolved in dichloromethane B and placed in a constant pressure dropping funnel, magnetic stirring, uniform speed drop is added at the same time under UV lamp, wavelength is 355 nm, light intensity is 400 mJ / cm 2 , irradiation for 10 min; after the reaction is completed, the reaction device is removed, and vacuum distillation is performed to obtain an intermediate product I;

[0165] The amount ratio of trimethylolpropane tris(3-mercaptopropionate) and 9-decen-1-ol is 1 mol:1 mol;

[0166] The amount ratio of trimethylolpropane tris(3-mercaptopropionate) and dichloromethane A is 1 mol:1200 mL;

[0167] The amount ratio of 9-decen-1-ol and dichloromethane B is 1 mol:450 mL;

[0168] The amount of photoinitiator 2959 is 1wt% of the total mass of the reactants in step S1.

[0169] S2: The intermediate product I, triethylamine, dichloromethane C are added to a flask, stirring, heptafluorobutyryl chloride, dichloromethane D is placed in a constant pressure dropping funnel, ice bath, magnetic stirring, uniform speed drop, after drop is completed, continue stirring for 10 h; stop stirring, stand, filter, take the filtrate, wash with 20wt% dilute hydrochloric acid solution for 3 times, wash with saturated sodium bicarbonate aqueous solution for 3 times, and then wash with deionized water A for 3 times, stand, separate, take the organic phase, add anhydrous sodium sulfate to dry, filter, take the filtrate, vacuum distillation, vacuum drying at 50℃ until constant weight, to obtain an intermediate product II;

[0170] The amount ratio of the intermediate product I, triethylamine, heptafluorobutyryl chloride is 1 mol:1 mol:1 mol;

[0171] The amount ratio of the intermediate product I and dichloromethane C is 1 mol:1660 mL;

[0172] The amount ratio of heptafluorobutyryl chloride and dichloromethane D is 1 mol:700 mL.

[0173] S3: N2 protection, 5-formyluracil, allylamine, anhydrous magnesium sulfate, dichloromethane E are added to a three-necked flask, stirring at 20℃ for 20 h, then filtering, taking the filtrate, vacuum distillation, vacuum drying at room temperature, to obtain an intermediate product III;

[0174] The amount ratio of 5-formyluracil, allylamine, anhydrous magnesium sulfate is 1 mol:1 mol:1 mol;

[0175] 5-formyluracil and dichloromethane E are used in a ratio of 1 mol: 420 mL.

[0176] S4: Intermediate product II, photoinitiator 2959, dichloromethane F are added into a flask, intermediate product III is dissolved in dichloromethane G and placed in a constant pressure dropping funnel, magnetic stirring, uniform speed dropping is added at the same time, placed under UV lamp, wavelength is 355 nm, light intensity is 400 mJ / cm 2 , irradiation is performed for 8 min; after the reaction is completed, the reaction device is removed, and vacuum distillation is performed to obtain target product IV, i.e., A1 raw material;

[0177] Intermediate product II and intermediate product III are used in a ratio of 1 mol: 1 mol;

[0178] Intermediate product II and dichloromethane F are used in a ratio of 1 mol: 2360 mL;

[0179] Intermediate product III and dichloromethane G are used in a ratio of 1 mol: 600 mL;

[0180] The amount of photoinitiator 2959 is 1 wt% of the total mass of the reactants in step S4.

[0181] Example 5

[0182] The present embodiment provides a preparation method of an aqueous humor drainage device, comprising the following steps:

[0183] A component, a B component, and a photoinitiator TPO-L are mixed, injected into a microfluidic mold, irradiated with ultraviolet light with a wavelength of 355 nm for 30 s, and placed in 37℃ physiological saline for oscillation for 7 d to obtain an aqueous humor drainage device for glaucoma.

[0184] The A component comprises A1 raw material and A2 raw material; the amount of A1 raw material and A2 raw material is 0.04 mol: 0.96 mol;

[0185] The A2 raw material is a mixture of ethylene glycol bis(3-mercaptopropionate) and trimethylolpropane tris(3-mercaptopropionate) in a molar ratio of 0.6:0.4.

[0186] The B component comprises B1 raw material and B2 raw material; the amount of B1 raw material and B2 raw material is 2 g: 8 g;

[0187] The B1 raw material is 2-phenylethyl methacrylate.

[0188] The amount of the A component and the B component is in a molar ratio of mercapto group to carbon-carbon double bond of 1:0.97; the amount of the photoinitiator TPO-L is 0.5 wt% of the total mass of the reactants.

[0189] The preparation method of the above-mentioned A1 raw material is as follows:

[0190] S1: Trimethylolpropane tris(3-mercaptopropionate), photoinitiator TPO-L, dichloromethane A were added into a flask, 9-decen-1-ol was dissolved in dichloromethane B and placed in a constant pressure dropping funnel, magnetic stirring, uniform speed drop was added at the same time under UV lamp, wavelength was 355 nm, light intensity was 400 mJ / cm2, irradiation was 5 min; after the reaction was completed, the reaction device was removed, and vacuum distillation was performed to obtain an intermediate product I; 2

[0191] The amount ratio of trimethylolpropane tris(3-mercaptopropionate) and 9-decen-1-ol was 1 mol: 1 mol.

[0192] The amount ratio of trimethylolpropane tris(3-mercaptopropionate) and dichloromethane A was 1 mol: 1200 mL; the amount ratio of 9-decen-1-ol and dichloromethane B was 1 mol: 450 mL.

[0193] The amount of photoinitiator TPO-L was 1 wt% of the total mass of the reactants in step S1.

[0194] S2: The intermediate product I, triethylamine, dichloromethane C were added into a flask, stirring, heptafluorobutyryl chloride, dichloromethane D was placed in a constant pressure dropping funnel, ice bath, magnetic stirring, uniform speed drop was added, after the drop was completed, stirring was continued for 10 h; stirring was stopped, and standing, filtration, taking the filtrate, washing with 20 wt% dilute hydrochloric acid solution for 3 times, washing with saturated sodium bicarbonate aqueous solution for 3 times, and then washing with deionized water A for 3 times, standing, liquid separation, taking the organic phase, adding anhydrous sodium sulfate for drying, filtration, taking the filtrate, vacuum distillation, vacuum drying at 50℃ until constant weight, to obtain an intermediate product II;

[0195] The amount ratio of the intermediate product I, triethylamine, and heptafluorobutyryl chloride was 1 mol: 1 mol: 1 mol.

[0196] The amount ratio of the intermediate product I and dichloromethane C was 1 mol: 1370 mL.

[0197] The amount ratio of heptafluorobutyryl chloride and dichloromethane D was 1 mol: 700 mL.

[0198] S3: N2 protection, 5-formyluracil, allylamine, anhydrous magnesium sulfate, dichloromethane E were added into a three-necked flask, stirring at 20℃ for 20 h, then filtration, vacuum distillation, vacuum drying at room temperature, to obtain an intermediate product III;

[0199] The amount ratio of 5-formyluracil, allylamine, and anhydrous magnesium sulfate was 1 mol: 1 mol: 1 mol. ​

[0200] 5-formyluracil and dichloromethane E are used in a ratio of 1 mol: 420 mL.

[0201] S4: Intermediate product II, photoinitiator TPO-L, dichloromethane F are added to the flask, intermediate product III is dissolved in dichloromethane G and placed in a constant pressure dropping funnel, magnetic stirring, uniform speed drop while placed under UV lamp, wavelength is 355 nm, light intensity is 400 mJ / cm 2 , irradiation for 5 min; after the reaction is completed, remove the reaction device, reduce pressure distillation to obtain the target product IV, i.e. A1 raw material;

[0202] The amount of intermediate product II and intermediate product III is 1 mol: 1 mol.

[0203] The amount of intermediate product II and dichloromethane F is 1 mol: 2070 mL.

[0204] The amount of intermediate product III and dichloromethane G is 1 mol: 600 mL.

[0205] The amount of photoinitiator TPO-L is 1wt% of the total mass of the reactants in step S4.

[0206] Example 6

[0207] The present embodiment provides a preparation method of aqueous humor drainage device, comprising the following steps:

[0208] A component, B component and photoinitiator TPO-L are mixed and injected into a microfluidic mold, and then irradiated by ultraviolet light with a wavelength of 355 nm for 30 s. After curing, the aqueous humor drainage device for glaucoma is obtained by oscillating in 37℃ physiological saline for 7 days.

[0209] The A component includes A1 raw material and A2 raw material; the amount of A1 raw material and A2 raw material is 0.05 mol: 0.95 mol.

[0210] The A2 raw material is a mixture of 3-mercapto-β, 4-dimethylcyclohexane ethanethiol and ethylene glycol bis(3-mercaptopropionate) in a molar ratio of 0.8:0.2.

[0211] The B component includes B1 raw material and B2 raw material; the amount of B1 raw material and B2 raw material is 2g:8g.

[0212] The B1 raw material is a mixture of ethyl acrylate and 2-phenylethyl methacrylate in a mass ratio of 1.4:0.6.

[0213] The amount of A component and B component is 1:0.97 in molar ratio of mercapto group to carbon-carbon double bond; the amount of photoinitiator TPO-L is 0.5wt% of the total mass of the reactants.

[0214] The preparation method of the above A1 raw material is as follows:

[0215] S1: Trimethylolpropane tris(3-mercaptopropionate), photoinitiator TPO-L, dichloromethane A are added to a flask, undecylenic alcohol is dissolved in dichloromethane B and placed in a constant pressure dropping funnel, magnetic stirring, uniform speed dropwise adding at the same time under UV lamp, wavelength is 355 nm, light intensity is 400 mJ / cm 2 , irradiation for 5 min; after the reaction is completed, the reaction device is removed, and vacuum distillation is performed to obtain an intermediate product I;

[0216] The amount ratio of trimethylolpropane tris(3-mercaptopropionate) and undecylenic alcohol is 1 mol:1 mol;

[0217] The amount ratio of trimethylolpropane tris(3-mercaptopropionate) and dichloromethane A is 1 mol:610 mL;

[0218] The amount ratio of undecylenic alcohol and dichloromethane B is 1 mol:510 mL;

[0219] The amount of photoinitiator TPO-L is 1 wt% of the total mass of the reactants in step S1.

[0220] S2: The intermediate product I, triethylamine, dichloromethane C are added to a flask, stirring, heptafluorobutyryl chloride, dichloromethane D is placed in a constant pressure dropping funnel, ice bath, magnetic stirring, uniform speed dropwise adding, after dropwise adding is completed, continue stirring for 12 h; stop stirring, stand, filter, take the filtrate, wash with 20 wt% dilute hydrochloric acid solution for 3 times, wash with saturated sodium bicarbonate aqueous solution for 3 times, and then wash with deionized water A for 3 times, stand, separate, take the organic phase, add anhydrous sodium sulfate for drying, filter, take the filtrate, vacuum distillation, vacuum drying at 50℃ until constant weight, to obtain an intermediate product II;

[0221] The amount ratio of the intermediate product I, triethylamine and heptafluorobutyryl chloride is 1 mol:1 mol:1 mol;

[0222] The amount ratio of the intermediate product I and dichloromethane C is 1 mol:1140 mL;

[0223] The amount ratio of heptafluorobutyryl chloride and dichloromethane D is 1 mol:700 mL.

[0224] S3: N2 protection, 5-formyluracil, allylamine, anhydrous magnesium sulfate, dichloromethane E are added to a three-necked flask, stirring at 20℃ for 20 h, then filtering, taking the filtrate, vacuum distillation, vacuum drying at room temperature, to obtain an intermediate product III;

[0225] 5-formyluracil, allylamine, anhydrous magnesium sulfate, the ratio of the amount of use is 1 mol: 1 mol: 1 mol;

[0226] 5-formyluracil and dichloromethane E, the ratio of the amount of use is 1 mol: 420 mL.

[0227] S4: the intermediate product II, the photoinitiator TPO-L, dichloromethane F are added to the flask, the intermediate product III is dissolved in dichloromethane G and placed in the constant pressure dropping funnel, magnetically stirred, and dropped at a constant speed while placed under the UV lamp, the wavelength is 355 nm, the light intensity is 400 mJ / cm 2 , irradiation for 5 min; after the reaction is completed, remove the reaction device, and distill under reduced pressure to obtain the target product IV, i.e. the A1 raw material;

[0228] The amount of use of the intermediate product II and the intermediate product III is 1 mol: 1 mol.

[0229] The amount of use of the intermediate product II and dichloromethane F is 1 mol: 1840 mL.

[0230] The amount of use of the intermediate product III and dichloromethane G is 1 mol: 600 mL.

[0231] The amount of use of the photoinitiator TPO-L is 1 wt% of the total mass of the reactants in step S4.

[0232] Example 7

[0233] The present embodiment provides a preparation method of an aqueous humor drainage device, comprising the following steps:

[0234] The A component, the B component, and the photoinitiator 2959 are mixed and injected into a microfluidic mold, irradiated by ultraviolet light with a wavelength of 355 nm for 30 s, and then placed in 37℃ physiological saline for oscillation for 7 d to obtain the aqueous humor drainage device for glaucoma.

[0235] The A component includes an A1 raw material and an A2 raw material; the amount of use of the A1 raw material and the A2 raw material is 0.02 mol: 0.98 mol.

[0236] The A2 raw material is a mixture of bicyclo[2.2.1]heptane-2,3-dithiol and ethylene glycol bis(3-mercaptopropionate) in a molar ratio of 0.5:0.5.

[0237] The B component includes a B1 raw material and a B2 raw material; the amount of use of the B1 raw material and the B2 raw material is 2 g: 8 g.

[0238] The B1 raw material is a mixture of triallyl isocyanurate and ethyl acrylate in a mass ratio of 0.8:1.2.

[0239] The ratio of the A component to the B component is 1:0.95 in terms of the molar ratio of the mercapto group to the carbon-carbon double bond; and the amount of the photoinitiator 2959 is 1.5 wt% of the total mass of the reactants.

[0240] The preparation method of the A1 raw material is as follows:

[0241] S1: Trimethylolpropane tris(3-mercaptopropionate), photoinitiator 184, dichloromethane A are added to a flask, 9-decen-1-ol is dissolved in dichloromethane B and placed in a constant-pressure dropping funnel, magnetic stirring is performed, and uniform-speed dropping is performed under a UV lamp with a wavelength of 355 nm and an intensity of 400 mJ / cm 2 , and irradiation is performed for 10 min; after the reaction is completed, the reaction device is removed, and vacuum distillation is performed to obtain an intermediate product I;

[0242] The ratio of trimethylolpropane tris(3-mercaptopropionate) to 9-decen-1-ol is 1 mol:1 mol;

[0243] The ratio of trimethylolpropane tris(3-mercaptopropionate) to dichloromethane A is 1 mol:1200 mL;

[0244] The ratio of 9-decen-1-ol to dichloromethane B is 1 mol:450 mL;

[0245] The amount of the photoinitiator 184 is 1 wt% of the total mass of the reactants in step S1.

[0246] S2: The intermediate product I, triethylamine, dichloromethane C are added to a flask, stirring is performed, perfluorooctanoyl chloride, dichloromethane D is placed in a constant-pressure dropping funnel, ice-bath cooling is performed, magnetic stirring is performed, uniform-speed dropping is performed, after the dropping is completed, stirring is continued for 8 h; stirring is stopped, standing is performed, filtration is performed, the filtrate is taken, 20 wt% dilute hydrochloric acid solution is added for washing 3 times, saturated sodium bicarbonate aqueous solution is added for washing 3 times, deionized water A is added for washing 3 times, standing is performed, liquid separation is performed, the organic phase is taken, anhydrous sodium sulfate is added for drying, filtration is performed, the filtrate is taken, vacuum distillation is performed, and vacuum drying is performed at 50°C until the weight is constant to obtain an intermediate product II;

[0247] The ratio of the intermediate product I, triethylamine, and perfluorooctanoyl chloride is 1 mol:1 mol:1 mol;

[0248] The ratio of the intermediate product I to dichloromethane C is 1 mol:1080 mL;

[0249] The ratio of perfluorooctanoyl chloride to dichloromethane D is 1 mol:1300 mL.

[0250] S3: N2 protection, 5-formyluracil, allylamine, anhydrous magnesium sulfate, dichloromethane E were added into a three-necked flask, stirred at 20°C for 20h, then filtered, the filtrate was distilled under reduced pressure, and vacuum dried at room temperature to obtain intermediate product III;

[0251] The amount ratio of 5-formyluracil, allylamine, and anhydrous magnesium sulfate was 1 mol: 1 mol: 1 mol;

[0252] The amount ratio of 5-formyluracil and dichloromethane E was 1 mol: 420 mL.

[0253] S4: Intermediate product II, photoinitiator 184, dichloromethane F were added into a flask, intermediate product III was dissolved in dichloromethane G and placed in a constant pressure dropping funnel, magnetically stirred, and dropped at a constant speed while placed under a UV lamp with a wavelength of 355 nm and a light intensity of 400 mJ / cm 2 , and irradiated for 8 min; after the reaction was completed, the reaction device was removed, and distilled under reduced pressure to obtain the target product IV, i.e., A1 raw material;

[0254] The amount ratio of intermediate product II and intermediate product III was 1 mol: 1 mol;

[0255] The amount ratio of intermediate product II and dichloromethane F was 1 mol: 2380 mL;

[0256] The amount ratio of intermediate product III and dichloromethane G was 1 mol: 600 mL;

[0257] The amount of photoinitiator 184 was 1 wt% of the total mass of the reactants in step S4.

[0258] Example 8

[0259] The present embodiment provides a preparation method of an aqueous humor drainage device, comprising the following steps:

[0260] A component, a B component, and a photoinitiator 184 were mixed and injected into a microfluidic mold, and then irradiated with ultraviolet light with a wavelength of 355 nm for 30 s, and after curing, placed in a 37°C physiological saline solution for oscillation for 7 d to obtain an aqueous humor drainage device for glaucoma.

[0261] The A component comprises an A1 raw material and an A2 raw material; the amount ratio of the A1 raw material and the A2 raw material is 0.02 mol: 0.98 mol;

[0262] The A2 raw material is ethylene glycol bis(3-mercaptopropionate).

[0263] The B component comprises a B1 raw material and a B2 raw material; the amount ratio of the B1 raw material and the B2 raw material is 2 g: 8 g;

[0264] The above-mentioned B1 raw material is 2-phenylethyl methacrylate.

[0265] The ratio of the above-mentioned A component to the B component is 1:0.99 in terms of the molar ratio of the mercapto group to the carbon-carbon double bond; and the amount of the photoinitiator 184 is 1wt% of the total mass of the reactants.

[0266] The preparation method of the above-mentioned A1 raw material is as follows:

[0267] S1: Trimethylolpropane tris(3-mercaptopropionate), photoinitiator 184, dichloromethane A are added to a flask, 9-decen-1-ol is dissolved in dichloromethane B and placed in a constant-pressure dropping funnel, magnetic stirring is performed, and uniform-speed dropping is performed under a UV lamp with a wavelength of 355nm and a light intensity of 400mJ / cm 2 , and irradiation is performed for 5min; after the reaction is completed, the reaction device is removed, and vacuum distillation is performed to obtain an intermediate product I;

[0268] The ratio of trimethylolpropane tris(3-mercaptopropionate) to 9-decen-1-ol is 1mol:1mol;

[0269] The ratio of trimethylolpropane tris(3-mercaptopropionate) to dichloromethane A is 1mol:710mL;

[0270] The ratio of 9-decen-1-ol to dichloromethane B is 1mol:450mL;

[0271] The amount of the photoinitiator 184 is 1wt% of the total mass of the reactants in step S1.

[0272] S2: The intermediate product I, triethylamine, dichloromethane C are added to a flask, stirring is performed, perfluorooctanoyl chloride, dichloromethane D is placed in a constant-pressure dropping funnel, ice-bath cooling is performed, magnetic stirring is performed, uniform-speed dropping is performed, after the dropping is completed, stirring is continued for 8h; the stirring is stopped, and standing is performed, filtration is performed, the filtrate is taken, 20wt% dilute hydrochloric acid solution is added for washing 3 times, saturated sodium bicarbonate aqueous solution is added for washing 3 times, deionized water A is added for washing 3 times, standing is performed, liquid separation is performed, the organic phase is taken, anhydrous sodium sulfate is added for drying, filtration is performed, the filtrate is taken, vacuum distillation is performed, and vacuum drying is performed at 50℃ until the constant weight to obtain an intermediate product II;

[0273] The ratio of the intermediate product I, triethylamine, perfluorooctanoyl chloride is 1mol:1mol:1mol;

[0274] The ratio of the intermediate product I to dichloromethane C is 1mol:1180mL;

[0275] The ratio of perfluorooctanoyl chloride to dichloromethane D is 1mol:1300mL.

[0276] S3: N2 protection, 5-formyluracil, allylamine, anhydrous magnesium sulfate, dichloromethane E were added into a three-necked flask, stirred at 20℃ for 20h, then filtered, the filtrate was distilled under reduced pressure, and vacuum dried at room temperature to obtain the intermediate product III;

[0277] The amount ratio of 5-formyluracil, allylamine and anhydrous magnesium sulfate was 1 mol: 1 mol: 1 mol;

[0278] The amount ratio of 5-formyluracil and dichloromethane E was 1 mol: 420 mL.

[0279] S4: The intermediate product II, photoinitiator 184 and dichloromethane F were added into a flask, the intermediate product III was dissolved in dichloromethane G and placed in a constant pressure dropping funnel, and then magnetically stirred, while dropping at a constant speed, placed under a UV lamp with a wavelength of 355 nm and an intensity of 400 mJ / cm 2 , and irradiated for 10 min; after the reaction was completed, the reaction device was removed, and distilled under reduced pressure to obtain the target product IV, i.e. the A1 raw material;

[0280] The amount ratio of the intermediate product II and the intermediate product III was 1 mol: 1 mol;

[0281] The amount ratio of the intermediate product II and dichloromethane F was 1 mol: 2480 mL;

[0282] The amount ratio of the intermediate product III and dichloromethane G was 1 mol: 600 mL;

[0283] The amount of photoinitiator 184 was 1 wt% of the total mass of the reactants in step S4.

[0284] The aqueous humor drainage devices provided by the following comparative examples of the present application are compared with example 1:

[0285] Comparative example 1

[0286] The difference between this comparative example and example 1 is that the amount ratio of the A component and the B component is 1:1.2 according to the molar ratio of the mercapto group to the carbon-carbon double bond.

[0287] Comparative example 2

[0288] The difference between this comparative example and example 1 is that the amount ratio of the A component and the B component is 1:0.8 according to the molar ratio of the mercapto group to the carbon-carbon double bond.

[0289] Comparative example 3

[0290] The difference between this comparative example and example 1 is that the A component only includes the A2 raw material.

[0291] Comparative example 4

[0292] The present comparative example differs from Example 1 in that the amount ratio of the A1 raw material to the A2 raw material is 0.1 mol:0.9 mol.

[0293] Comparative Example 5

[0294] The present comparative example differs from Example 1 in that the B component only includes the B2 raw material.

[0295] Comparative Example 6

[0296] The present comparative example differs from Example 1 in that the amount ratio of the B1 raw material to the B2 raw material is 4 g:6 g.

[0297] Comparative Example 7

[0298] The present comparative example differs from Example 1 in that the B2 raw material is gelatin, i.e., the gelatin is not modified.

[0299] Comparative Example 8

[0300] The present comparative example differs from Example 1 in that the A1 raw material is 5-formyluracil.

[0301] Comparative Example 9

[0302] The present comparative example differs from Example 1 in that the A1 raw material is prepared as follows:

[0303] S1: N2 protection, 5-formyluracil, allylamine, anhydrous magnesium sulfate, dichloromethane E are added to a three-necked flask, stirred at 20°C for 20h, filtered, the filtrate is taken, distilled under reduced pressure, vacuum dried at room temperature to obtain intermediate product I;

[0304] The amount ratio of 5-formyluracil, allylamine, anhydrous magnesium sulfate is 1 mol:1 mol:1 mol;

[0305] The amount ratio of 5-formyluracil and dichloromethane E is 1 mol:420 mL.

[0306] S2: trimethylolpropane tris(3-mercaptopropionate), photoinitiator TPO-L, dichloromethane F are added to a flask, intermediate product I is dissolved in dichloromethane G and placed in a constant pressure dropping funnel, magnetically stirred, and dropped at a uniform speed while being placed under a UV lamp with a wavelength of 355 nm and a light intensity of 400 mJ / cm 2 , irradiated for 5 min; after the reaction is completed, the reaction device is removed and distilled under reduced pressure to obtain the target product;

[0307] The amount ratio of trimethylolpropane tris(3-mercaptopropionate) and intermediate product I is 1 mol:1 mol.

[0308] The amount ratio of trimethylolpropane tri(3-mercaptopropionate) to dichloromethane F is 1 mol: 1200 mL;

[0309] The amount ratio of intermediate product I to dichloromethane G is 1 mol: 1660 mL;

[0310] The amount of photoinitiator TPO-L is 1 wt% of the total mass of the reactants in step S2.

[0311] Comparative Example 10

[0312] The difference between this comparative example and Example 1 is that the preparation method of A1 raw material is as follows:

[0313] S1: Trimethylolpropane tri(3-mercaptopropionate), photoinitiator TPO-L, dichloromethane A were added to a flask, 9-decen-1-ol was dissolved in dichloromethane B and placed in a constant pressure dropping funnel, magnetic stirring, uniform speed drop, and placed under a UV lamp at the same time, wavelength 355 nm, light intensity 400 mJ / cm 2 , irradiation for 5 min; after the reaction was completed, the reaction device was removed, and vacuum distillation was performed to obtain intermediate product I;

[0314] The amount ratio of trimethylolpropane tri(3-mercaptopropionate) to 9-decen-1-ol is 1 mol: 1 mol;

[0315] The amount ratio of trimethylolpropane tri(3-mercaptopropionate) to dichloromethane A is 1 mol: 1200 mL;

[0316] The amount ratio of 9-decen-1-ol to dichloromethane B is 1 mol: 450 mL;

[0317] The amount of photoinitiator TPO-L is 1 wt% of the total mass of the reactants in step S1.

[0318] S2: Intermediate product I, triethylamine, dichloromethane C were added to a flask, stirring, perfluorooctyl chloride, dichloromethane D was placed in a constant pressure dropping funnel, ice bath, magnetic stirring, uniform speed drop, after the drop was completed, stirring was continued for 8 h; stop stirring, stand, filter, take the filtrate, wash with 20 wt% dilute hydrochloric acid solution for 3 times, wash with saturated sodium bicarbonate aqueous solution for 3 times, and then wash with deionized water A for 3 times, stand, separate, take the organic phase, add anhydrous sodium sulfate to dry, filter, take the filtrate, vacuum distillation, vacuum drying at 50℃ until constant weight to obtain the target product;

[0319] The amount ratio of intermediate product I, triethylamine, perfluorooctyl chloride is 1 mol: 1 mol: 1 mol;

[0320] The amount ratio of intermediate product I to dichloromethane C is 1 mol: 1660 mL;

[0321] The ratio of the amount of perfluorooctanoyl chloride to dichloromethane D is 1 mol: 1300 mL.

[0322] The performance of the aqueous humor drainage device prepared in each embodiment of the present application and the comparative example was determined respectively, and the test method was as follows:

[0323] (1) Cell inhibition effect test:

[0324] 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 by mass fraction. After the fibroblasts were precipitated, the migration test was inserted into the glaucoma drainage tube, so that it was completely immersed in the medium. After 5 days of culture, the state of the fibroblasts was detected by live / dead staining and CCK-8, and the 5-day fibroblast (HTF) live / dead ratio was calculated. The higher the activity of the fibroblasts, the more serious the scarring.

[0325] (2) Cell adhesion test:

[0326] 3T3 mouse embryonic bromoblasts were stored in T-75 Falcon cell culture, using sterile Dulbecco's modified Falcon medium (DMEM) containing 10% fetal bovine serum (FBS) by mass fraction and 100 units / ml penicillin and 0.1 mg / ml streptomycin. 6 samples of each covering (a total of 36 samples) were placed in a 6-well tissue culture plate and irradiated under ultraviolet light for 10-15 minutes. Cells were seeded onto the covering membrane at a density of about 11,000 cells / cm. Then the cells were incubated at 37°C, 5% carbon dioxide for 24 h, and then the culture medium was poured out and washed once with PBS. The number of adherent cells was defined as the number of living cells per 100* field. The percentage of control was calculated by multiplying the ratio of the percentage of living cells on the treated substrate to the percentage of living cells on the untreated substrate by 100 to calculate the adhesion force. The average control adhesion rate of each sample group was determined, and statistical comparison of the viability determination was made in the above-mentioned method.

[0327] (3) Water contact angle: The raw materials in the examples were injected into a film according to the ratio, and the test was performed according to GB / T 30693-2014.

[0328] (4) Monomer residue test: gas chromatography was used for testing. The monomer residue indicating method: <1 ppm is recorded as "OK"; >1 ppm is recorded as "NG".

[0329] (5) Mechanical strength test: the drainage tube was folded in half, and the presence or absence of cracks and creases was observed. The mechanical strength indicating method: no cracks and no creases are recorded as "O", no cracks and creases are recorded as "◎", and cracks and creases are recorded as "●".

[0330] (6) Elastic modulus test: the raw materials in the examples were injected into 5B dumbbell-shaped mold according to the ratio, and cured, and tested according to GB / T 1040.3-2006.

[0331] (7) Drainage efficiency test: 10 ml of deionized water was passed through the drainage tube at a constant flow rate (64 microliters / min), and the time required for the complete flow of the deionized water was recorded to determine the drainage efficiency.

[0332] The test results are shown in Table 1:

[0333] .

[0334] Firstly, from Table 1, Examples 1-8 and Comparative Examples 1-10, it can be seen that the aqueous humor drainage devices prepared in each of the examples of the present application all have excellent anti-cell proliferation and anti-cell adhesion properties, as well as suitable water contact angles (hydrophilicity) and drainage efficiency, excellent mechanical properties, and extremely low monomer residues.

[0335] Secondly, from Examples 1 and Comparative Examples 1-2, it can be observed that adjusting the reaction ratio of the thiol group and the carbon-carbon double bond, and the excess of any component, will result in poor mechanical properties of the prepared drainage tube.

[0336] Thirdly, from Examples 1 and Comparative Examples 3-4, it can be observed that the lack of functional raw material A1 in component A will result in the loss of anti-cell proliferation and anti-cell adhesion properties, and an excess will result in poor hydrophilicity.

[0337] Fourthly, from Examples 1 and Comparative Examples 5-7, it can be observed that the unreasonable amount of B1 raw material in component B will affect the mechanical properties; using unmodified gelatin as a filler, and the crosslinking density of the thiol and olefin material reaction being too large, it is difficult to form, and the drainage tube cannot be prepared.

[0338] Fifthly, from Examples 1 and Comparative Examples 8-10, it can be observed that the addition of only 5-formyluracil will result in poor anti-cell adhesion and excessive monomer residues; the addition of only thiol-modified 5-formyluracil will also result in poor anti-cell adhesion, and there is a risk of drainage tube blockage; and the addition of only thiol-modified fluorine-containing structure will result in insufficient anti-cell proliferation, the HTFs fibroblast live / dead ratio increases after 5 days, and the risk of scarring increases.

[0339] Based on the above ideal examples according to the present application, through the above description, relevant personnel can make various changes and modifications without deviating from the technical concept of the present application. The technical scope of the present application is not limited to the contents of the specification, and must be determined by the scope of the claims.

Claims

1. A photocurable material, characterized in that, It consists of component A, component B and photoinitiator I; The A component comprises raw material A1 and raw material A2; The A1 raw material contains an anti-metabolic structure, F element, and thiol group; The A2 raw material is a mercapto-containing compound; The B component includes raw material B1 and raw material B2; The B1 raw material is selected from at least one of triallyl isocyanurate, trimethylolpropane triacrylate, ethyl acrylate, and 2-phenylethyl methacrylate; The B2 raw material is modified gelatin; The A1 raw material is prepared according to the following method: S1: Trimethylolpropane tris(3-mercaptopropionate), photoinitiator II, and dichloromethane A are mixed to obtain mixture I; an unsaturated alcohol is dissolved in dichloromethane B to obtain mixture II; under UV lamp irradiation, mixture II is added dropwise to mixture I to carry out the reaction; after the reaction is completed, the mixture is distilled under reduced pressure to obtain intermediate product I; S2: Mix the intermediate product I, triethylamine, and dichloromethane C to obtain mixture III; mix perfluoroalkyl acyl chloride and dichloromethane D under ice bath conditions to obtain mixture IV; add mixture IV dropwise to mixture III, stir, react, let stand, filter, take the filtrate, and wash; After standing, the liquid was separated, the organic phase was collected, dried, filtered, and the filtrate was collected, then distilled under reduced pressure and dried under vacuum to constant weight to obtain intermediate product II; S3: Under inert gas protection, 5-formyluracil, allylamine, anhydrous magnesium sulfate, and dichloromethane E were mixed, stirred at 20°C, filtered, and the filtrate was distilled under reduced pressure and dried under vacuum at room temperature to obtain intermediate product III. S4: Mix the intermediate product II, photoinitiator III, and dichloromethane F to obtain mixture V; dissolve the intermediate product III in dichloromethane G to obtain mixture VI; add mixture VI dropwise to mixture V under UV lamp irradiation to carry out the reaction; after the reaction is completed, distill under reduced pressure to obtain raw material A1; The molar ratio of raw material A1 to raw material A2 in component A is (0.01-0.05):(0.95-0.99). The perfluoroalkyl acyl chloride is selected from at least one of heptafluorobutyroyl chloride and perfluorooctanoyl chloride; The A2 raw material is selected from at least one of 3-mercapto-β,4-dimethylcyclohexanethiol, bicyclo[2.2.1]heptane-2,3-dithiol, ethylene glycol bis(3-mercaptopropionate), and trimethylolpropane tri(3-mercaptopropionate).

2. The photocurable material as described in claim 1, characterized in that, The antimetabolite structure is a thymine structure.

3. The photocurable material as described in claim 1, characterized in that, The unsaturated alcohol is selected from at least one of 9-decen-1-ol, undecenol, and 5-hexenyl-1-ol.

4. The photocurable material as described in claim 1, characterized in that, In step S1, the molar ratio of trimethylolpropane tris(3-mercaptopropionate) to the unsaturated alcohol is 1:(0.8-1.2); the amount of photoinitiator II in step S1 is 1 wt% of the total mass of the reactants in step S1.

5. The photocurable material as described in claim 1, characterized in that, In step S2, the molar ratio of intermediate product I, triethylamine, and perfluoroalkyl acyl chloride is 1:(0.8-1.2):(0.8-1.2).

6. The photocurable material as described in claim 1, characterized in that, In step S3, the molar ratio of 5-formyluracil, allylamine, and anhydrous magnesium sulfate is 1:(0.8-1.2):(0.8-1.2).

7. The photocurable material as described in claim 1, characterized in that, In step S4, the molar ratio of intermediate product II to intermediate product III is 1:1; the amount of photoinitiator III in step S4 is 1 wt% of the total mass of the reactants in step S4.

8. The photocurable material according to any one of claims 1-7, characterized in that, The mass ratio of raw material B1 to raw material B2 in component B is 1:

4.

9. The photocurable material according to any one of claims 1-7, characterized in that, The ratio of component A to component B is 1:(0.95-0.99) based on the molar ratio of thiol group to carbon-carbon double bond.

10. The photocurable material according to any one of claims 1-7, characterized in that, The amount of photoinitiator I is 0.5-1.5 wt% of the total mass of the reactants.

11. A type of aqueous humor drainage device, characterized in that, It is prepared by a photocuring method from the photocurable material as described in any one of claims 1-10.

12. A method for preparing the aqueous humor drainage device as described in claim 11, characterized in that, The process includes the following steps: injecting a photocurable material into a microfluidic mold, irradiating it with ultraviolet light, curing it, and then placing it in 37°C physiological saline for oscillation to obtain an aqueous humor drainage device.

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