Photo-curing material, aqueous humor drainage device and preparation method of aqueous humor drainage device

Abstract

The invention provides a photocuring material, an aqueous humor drainage device and a preparation method thereof, and relates to the technical field of medical instruments. The photocuring material is composed of a component A, a component B and a photoinitiator I, wherein the component A comprises a raw material A1 and a raw material A2; the raw material A1 simultaneously contains an anti-metabolic structure, an F element and sulfydryl; the A2 raw material is a sulfydryl-containing compound; the component B comprises a raw material B1 and a raw material B2; the raw material B1 is selected from at least one of triallyl isocyanurate, trimethylolpropane triacrylate, ethyl acrylate and methacrylic acid-2-phenyl ethyl ester; and the raw material B2 is modified gelatin. A sulfydryl-alkene material with good biocompatibility is adopted, an introduced anti-metabolism structure is combined with the F element, scar of a postoperative operation site can be effectively reduced, the good cell adsorption resistance is achieved, and the drainage efficiency is improved.

Description

Technical Field

[0001] The present invention relates to the technical field of medical devices, and in particular to a photocurable material and an aqueous humor drainage device and a preparation method thereof. Background Art

[0002] At present, most glaucoma diseases in clinical practice can be treated by controlling intraocular pressure through drainage device implantation. Drain implantation can reduce intraocular pressure and achieve controlled treatment of glaucoma.

[0003] There are three main ways to drain the aqueous humor with glaucoma drainage devices: subconjunctival drainage, Schlemm's canal drainage, and choroidal-scleral drainage. The key to the success of subconjunctival drainage surgery is to form a functional bleb. This type of surgery will also have some complications, such as scarring of the bleb and thinning of the bleb, which will result in failure of glaucoma surgery. The physiological pathway for aqueous humor outflow is mainly Schlemm's canal. The principle is to open up the physiological drainage channel from the anterior chamber to Schlemm's canal to achieve the purpose of aqueous humor drainage. At present, hospitals have adopted this method for surgery, but this drainage technique is not suitable for pigmented glaucoma with trabecular meshwork obstruction caused by pigment deposition and open-angle glaucoma with high subscleral venous pressure. Choroidal scleral drainage is a new method of aqueous humor drainage, which avoids some complications that may occur in functional bleb-dependent surgery, and is also suitable for pigmented glaucoma with trabecular meshwork obstruction caused by pigment deposition and open-angle glaucoma with high subscleral venous pressure that cannot be treated by Schlemm's canal drainage devices. However, there are few existing products for choroidal scleral drainage, and even fewer products for minimally invasive choroidal scleral drainage that are suitable for minimally invasive implantation.

[0004] The aqueous humor drain used to treat glaucoma is a tubular structure that can be minimally invasively implanted with an outer diameter of only 100-900μm and an inner diameter of 10-100μm. It is usually very small, soft and elastic, and can drain aqueous humor from the eye, thereby reducing intraocular pressure.

[0005] The research and development of aqueous humor drainage devices is very difficult. On the one hand, due to the extremely thin diameter of the minimally invasive glaucoma drainage tube, very high requirements are placed on the preparation process. The tube material is required to have suitable physical and chemical properties so that the drainage tube can be prepared. On the other hand, the raw materials must be safe, non-toxic, and non-allergic. In addition, the aqueous humor drainage device must have no foreign body sensation after implantation, have good compliance with the eye tissue, and have a good drainage and blood pressure-lowering effect.

[0006] Existing drainage tubes are usually prepared by photocuring using photocurable materials. Although the current photocurable materials can meet the performance requirements of drainage tubes having good compliance with eye tissues, safe use, and non-toxicity, they still have the problem of low drainage efficiency, which limits the application of drainage tubes. Summary of the invention

[0007] The technical problem to be solved by the present invention is: in order to solve the problem of low drainage efficiency of aqueous humor drainage devices in the prior art, the present invention provides a photocurable material, which simultaneously introduces F elements and anti-metabolic structures to reduce postoperative scarring at the surgical site while adjusting the hydrophilicity, 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 invention to solve its technical problem is: A photocurable material, comprising component A, component B and photoinitiator I; The A component includes A1 raw material and A2 raw material; The A1 raw material contains antimetabolism structure, F element and thiol group at the same time; The A2 raw material is a thiol-containing compound; The B component includes 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; The B2 raw material is modified gelatin.

[0009] Optionally, the anti-metabolite structure is a thymine structure.

[0010] Optionally, the A1 raw material is prepared according to the following method: S1: Mix trimethylolpropane tris(3-mercaptopropionate), photoinitiator II, and dichloromethane A to obtain a mixed solution I; dissolve unsaturated alcohol in dichloromethane B to obtain a mixed solution II; under UV light irradiation, dropwise add the mixed solution II to the mixed solution I to react; after the reaction is completed, perform vacuum distillation to obtain an intermediate product I; S2: Mix the intermediate product I, triethylamine and dichloromethane C to obtain a mixed solution III; mix perfluoroalkyl acyl chloride and dichloromethane D under ice bath conditions to obtain a mixed solution IV; dropwise add the mixed solution IV to the mixed solution III, stir, react, let stand, filter, take the filtrate, wash; let stand, separate the liquids, take the organic phase, dry, filter, take the filtrate, distill under reduced pressure, and vacuum dry to constant weight to obtain an intermediate product II; S3: Under inert gas protection, 5-formyluracil, allylamine, anhydrous magnesium sulfate and dichloromethane E are mixed, stirred at 20°C, filtered, and the filtrate is distilled under reduced pressure and dried under vacuum at room temperature to obtain intermediate III; S4: Mix the intermediate product II, photoinitiator III and dichloromethane F to obtain a mixed solution V; dissolve the intermediate product III in dichloromethane G to obtain a mixed solution VI; add the mixed solution VI dropwise to the mixed solution V under UV lamp irradiation to react; after the reaction is completed, perform reduced pressure distillation to obtain the A1 raw material.

[0011] Optionally, the unsaturated alcohol is selected from at least one of 9-decen-1-ol, undecenyl alcohol, and 5-hexenyl-1-ol.

[0012] Optionally, the perfluoroalkyl acyl chloride is selected from at least one of heptafluorobutyryl chloride and perfluorooctanoyl chloride.

[0013] Optionally, the molar ratio of trimethylolpropane tris(3-mercaptopropionate) to the unsaturated alcohol in step S1 is 1:(0.8-1.2); the amount of photoinitiator II in step S1 is 1wt% of the total mass of the reactants in step S1.

[0014] Optionally, in step S2, the molar ratio of the intermediate product I, the triethylamine, and the perfluoroalkyl acyl chloride is 1:(0.8-1.2):(0.8-1.2).

[0015] Optionally, in step S3, the molar ratio of the 5-formyluracil, the allylamine, and the anhydrous magnesium sulfate is 1:(0.8-1.2):(0.8-1.2).

[0016] Optionally, the molar ratio of the intermediate product II to 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.

[0017] Optionally, the A2 raw material is selected from at least one of 3-mercapto-β,4-dimethylcyclohexaneethanethiol, bicyclo[2.2.1]heptane-2,3-dithiol, ethylene glycol bis(3-mercaptopropionate), and trimethylolpropane tris(3-mercaptopropionate).

[0018] 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).

[0019] Optionally, the mass ratio of the B1 raw material to the B2 raw material in the B component is 1:4.

[0020] Optionally, the usage ratio of the component A to the component B is 1:(0.95-0.99) in terms of the molar ratio of the thiol group to the carbon-carbon double bond.

[0021] Optionally, the amount of the photoinitiator I is 0.5-1.5wt% of the total mass of the reactants.

[0022] Another object of the present invention is to provide an aqueous humor drainage device, which is prepared by a photocuring method using the photocurable material as described above.

[0023] Another object of the present invention is to provide a method for preparing the aqueous humor drainage device as described above, comprising the following steps: injecting a photocurable material into a microfluidic mold, irradiating it with ultraviolet light, and placing it in 37°C saline for oscillation after curing to obtain an aqueous humor drainage device.

[0024] The beneficial effects of the present invention are: The photocurable material provided by the present invention adopts a thiol-ene material with good biocompatibility, and can prepare an aqueous humor drainage device at room temperature or low temperature through photocuring technology, thereby avoiding damage to the material by thermal stress in a thermal curing process; by combining the introduced anti-metabolism structure with the F element, the scarring of the surgical site after surgery can be effectively reduced, the material has good resistance to cell adsorption, and the drainage efficiency is improved; 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 THE DRAWINGS

[0025] The present invention is further described below in conjunction with the accompanying drawings and embodiments.

[0026] Figure 1 is the infrared spectrum of the intermediate product I in Example 1 of the present invention; Figure 2 is the infrared spectrum of the intermediate product II in Example 1 of the present invention; Figure 3 is the infrared spectrum of the intermediate product III in Example 1 of the present invention; Figure 4 It is the infrared spectrum of raw material A1 in Example 1 of the present invention. DETAILED DESCRIPTION

[0027] 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.

[0028] In order to solve the problem of low drainage efficiency of aqueous humor drainage devices in the prior art, the present invention provides a photocurable material, which consists of an A component, a B component and a photoinitiator I; wherein the A component comprises an A1 raw material and an A2 raw material; the A1 raw material contains an anti-metabolism structure, an F element and a thiol group at the same time; the A2 raw material is a thiol-containing compound; the B component comprises a B1 raw material and a 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.

[0029] In order to ensure the smooth formation of the aqueous humor drainage device, the modified gelatin of the present invention is preferably prepared according to the following method: Mix gelatin with water, adjust the pH value of the solution to alkaline with alkali solution, then drop allyl glycidyl ether into the mixture for reaction, adjust the pH value of the reaction mixture to neutral with an acidic solution, dialyze for 3 days, and freeze-dry to obtain B2 raw material, i.e. modified gelatin; wherein the mass ratio of gelatin to allyl glycidyl ether is 20:1.

[0030] The A component of the photocurable material contains a mercapto group, and the B component contains a carbon-carbon double bond. Therefore, the present invention can prepare an aqueous humor drainage device from a mercapto-ene material by a photocuring method.

[0031] Since the aqueous humor drainage device needs to be implanted in the body for a long time during use, the proliferation of postoperative fibroblasts will block the aqueous humor drainage device during use, and the cells in the tissue fluid will also adhere to the aqueous humor drainage device, which will eventually lead to poor filtration effect and failure of the aqueous humor drainage device; based on this, the present invention introduces an anti-metabolism structure and F element into the system through A1 raw material at the same time, wherein the anti-metabolism structure can prevent cell division, has excellent anti-metabolism effect, can reduce scarring of the surgical site after surgery, and improve the drainage filtration effect; F element has low atomic surface energy, which can enrich the A1 raw material at the material interface, and combined with the anti-metabolism structure, the anti-metabolism effect is further improved; at the same time, the interface with a large amount of F element adjusts the hydrophilicity of the interface, so that it has good anti-cell adsorption, which helps to further improve the drainage efficiency; in addition, since the A1 raw material contains a thiol 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 free small molecules in the system, and avoiding damage to the body due to the presence of small molecules.

[0032] The photocurable material provided by the present invention adopts a thiol-ene material with good biocompatibility, and can prepare an aqueous humor drainage device at room temperature or low temperature through photocuring technology, thereby avoiding damage to the material by thermal stress in a thermal curing process; by combining the introduced anti-metabolism structure with the F element, the scarring of the surgical site after surgery can be effectively reduced, the material has good resistance to cell adsorption, and the drainage efficiency is improved; 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.

[0033] In order to ensure the anti-metabolic effect of the aqueous humor drainage device, the present invention preferably uses a thymine structure as the anti-metabolic structure, and utilizes the thymine structure to prevent cell division, reduce scarring of the surgical site after surgery, and improve the drainage and filtration effect.

[0034] Specifically, the preferred A1 raw material of the present invention is prepared according to the following method: S1: Trimethylolpropane tris(3-mercaptopropionate), photoinitiator II, and dichloromethane A are mixed to obtain a mixed solution I; unsaturated alcohol is dissolved in dichloromethane B to obtain a mixed solution II; under UV light irradiation, the mixed solution II is added dropwise to the mixed solution I to react; after the reaction is completed, the mixture is distilled under reduced pressure to obtain an intermediate product I; S2: Mix the intermediate product I, triethylamine and dichloromethane C to obtain a mixed solution III; mix perfluoroalkyl acyl chloride and dichloromethane D under ice bath conditions to obtain a mixed solution IV; add the mixed solution IV dropwise to the mixed solution III, stir, react, let stand, filter, take the filtrate, wash; let stand, separate the liquids, take the organic phase, dry, filter, take the filtrate, distill under reduced pressure, and vacuum dry to constant weight to obtain the intermediate product II; S3: Under inert gas protection, 5-formyluracil, allylamine, anhydrous magnesium sulfate and dichloromethane E are mixed, stirred at 20°C, filtered, and the filtrate is distilled under reduced pressure and dried under vacuum at room temperature to obtain intermediate III; S4: Mix the intermediate product II, photoinitiator III and dichloromethane F to obtain a mixed solution V; dissolve the intermediate product III in dichloromethane G to obtain a mixed solution VI; add the mixed solution VI dropwise into the mixed solution V under UV lamp irradiation to react; after the reaction is completed, perform reduced pressure distillation to obtain the target product IV, i.e., the A1 raw material.

[0035] The unsaturated alcohol is selected from at least one of 9-decen-1-ol, undecenyl alcohol and 5-hexenyl-1-ol; and the perfluoroalkyl acyl chloride is selected from at least one of heptafluorobutyryl chloride and perfluorooctanoyl chloride.

[0036] It should be noted that in the present invention, photoinitiator I, photoinitiator II, and photoinitiator III may be the same or different; in the present invention, preferably, photoinitiator I, photoinitiator II, and photoinitiator III are all selected from at least one of photoinitiator 2959, photoinitiator TPO-L, and photoinitiator 184.

[0037] Dichloromethane A, dichloromethane B, dichloromethane C, dichloromethane D, dichloromethane E, dichloromethane F, and dichloromethane G in the present invention are only marked for the convenience of distinction during the writing process and do not represent differences in performance or composition.

[0038] In order to take into account both the drainage efficiency and mechanical properties of the aqueous humor drainage device, the molar ratio of trimethylolpropane tris(3-mercaptopropionate) to the unsaturated alcohol in step S1 is preferably 1:(0.8-1.2); the amount of photoinitiator II in step S1 is 1wt% of the total mass of the reactants in step S1; the molar ratio of intermediate product I, triethylamine, and perfluoroalkyl acyl chloride in step S2 is preferably 1:(0.8-1.2):(0.8-1.2); the molar ratio of 5-formyluracil, allylamine, and anhydrous magnesium sulfate in step S3 is preferably 1:(0.8-1.2):(0.8-1.2); the molar ratio of intermediate product II to intermediate product III in step S4 is preferably 1:1; the amount of photoinitiator III in step S4 is 1wt% of the total mass of the reactants in step S4.

[0039] The preparation process of the A1 raw material is as follows: .

[0040] Wherein R is selected from at least one of (CH2)4, (CH2)8, (CH2)9; n is selected from at least one of 2 and 6.

[0041] In the present invention, the preferred raw material A2 is selected from at least one of 3-mercapto-β,4-dimethylcyclohexaneethanethiol, bicyclo[2.2.1]heptane-2,3-dithiol, ethylene glycol bis(3-mercaptopropionate), and trimethylolpropane tris(3-mercaptopropionate).

[0042] In order to take into account both the drainage efficiency and mechanical properties of the aqueous humor drainage device, the present invention preferably has a molar ratio of A1 raw material to A2 raw material in component A of (0.01-0.05): (0.95-0.99); and preferably has a mass ratio of B1 raw material to B2 raw material in component B of 1:4.

[0043] The present invention further preferably has a molar ratio of component A to component B in the photocurable material of 1:(0.95-0.99) based on the thiol group to carbon-carbon double bond ratio; preferably, the amount of photoinitiator I is 0.5-1.5wt% of the total mass of the reactants, that is, the amount of photoinitiator I is 0.5-1.5wt% of the total mass of component A and component B.

[0044] Another object of the present invention is to provide an aqueous humor drainage device, which is prepared from the above-mentioned photocurable material by a photocuring method.

[0045] The aqueous humor drainage device provided by the present invention is prepared at room temperature or low temperature by using a thiol-ene material with good biocompatibility through a photocuring technology, thereby being able to avoid damage to the material caused by thermal stress in a thermal curing process; by combining the introduced anti-metabolism structure with the F element, it is possible to effectively reduce scarring of the surgical site after surgery, so that the device has good resistance to cell adsorption and improves drainage efficiency; and, by introducing sulfur-containing materials and gelatin into the raw materials, it is helpful to make the aqueous humor drainage device have good biocompatibility and mechanical properties.

[0046] Another object of the present invention is to provide a method for preparing the aqueous humor drainage device as described above, the preparation method comprising the following steps: injecting a photocurable material into a microfluidic mold, irradiating it with ultraviolet light, and placing it in 37°C saline for oscillation after curing to obtain an aqueous humor drainage device.

[0047] The preparation method of the aqueous humor drainage device provided by the present invention is prepared at room temperature or low temperature by light curing technology, thereby avoiding damage to the material caused by thermal stress in the thermal curing process; by combining the introduced anti-metabolism structure with the F element, the scarring of the surgical site after surgery can be effectively reduced, so that the device has good resistance to cell adsorption and improves 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.

[0048] 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.

[0049] Unless otherwise specified, the modified gelatin in each embodiment of the present invention and the comparative example is prepared according to the following method: Mix 5 g of gelatin with 60 mL of water, adjust the pH value of the solution to 10.5 with a 3 mol / L sodium hydroxide aqueous solution, then drop 0.25 g of allyl glycidyl ether and react for 4 hours. Then adjust the pH of the reaction mixture to neutral with a 3 mol / L hydrochloric acid aqueous solution, dialyze for 3 days, and freeze-dry to obtain modified gelatin, i.e., B2 raw material.

[0050] In the following examples, the content of carbon-carbon double bonds in the raw materials was determined by iodine titration.

[0051] Example 1 This embodiment provides a method for preparing an aqueous humor drainage device, comprising the following steps: Component A, component B and photoinitiator 2959 were mixed, injected into a microfluidic mold, irradiated with ultraviolet light of a wavelength of 355 nm for 30 seconds, and placed in 37° C. physiological saline for oscillation for 7 days after curing to obtain an aqueous humor drainage device.

[0052] The above-mentioned component A includes raw material A1 and raw material A2; the usage ratio of raw material A1 to raw material A2 is 0.02 mol:0.98 mol; The above-mentioned A2 raw material is a mixture of 3-mercapto-β, 4-dimethylcyclohexaneethanethiol and ethylene glycol bis(3-mercaptopropionate) in a molar ratio of 0.5:0.5.

[0053] The above-mentioned B component includes B1 raw material and B2 raw material; the usage ratio of B1 raw material to B2 raw material is 2g:8g; The above B1 raw material is a mixture of triallyl isocyanurate and ethyl acrylate in a mass ratio of 0.6:1.4.

[0054] The usage ratio of the above-mentioned component A to component B is 1:0.99 in terms of the molar ratio of mercapto group to carbon-carbon double bond; the usage amount of the photoinitiator 2959 is 1.5wt% of the total mass of the reactants.

[0055] The preparation method of the above A1 raw material is as follows: S1: Add trimethylolpropane tris(3-mercaptopropionate), photoinitiator TPO-L, and dichloromethane A into a flask, dissolve 9-decene-1-ol in dichloromethane B, place in a constant pressure dropping funnel, stir magnetically, and place under a UV lamp with a wavelength of 355nm and a light intensity of 400mJ / cm 2 , irradiated for 5 min; after the reaction was completed, the reaction apparatus was removed and distilled under reduced pressure to obtain intermediate product I; The ratio of trimethylolpropane tris(3-mercaptopropionate) and 9-decen-1-ol is 1 mol:1 mol; The dosage ratio of trimethylolpropane tris(3-mercaptopropionate) to dichloromethane A is 1 mol:1200 mL; The dosage ratio of 9-decen-1-ol to dichloromethane B is 1 mol:450 mL; The amount of photoinitiator TPO-L used is 1wt% of the total mass of the reactants in step S1; See also Figure 1 As shown, the infrared data of intermediate product I are as follows: 3443 cm -1:-OH exists; 2550cm -1 :-SH exists and weakens; 1733 cm -1 :-C=O exists; 1631cm -1 :-C=C- does not exist.

[0056] S2: Add the intermediate product I, triethylamine, and dichloromethane C into a flask and stir. Place perfluorooctanoyl chloride and dichloromethane D in a constant pressure dropping funnel, place in an ice bath, stir magnetically, and dropwise add at a uniform speed. Continue stirring for 8 hours after the addition is completed. Stop stirring, let stand, filter, take the filtrate, add 20wt% dilute hydrochloric acid solution to wash 3 times, add saturated sodium bicarbonate aqueous solution to wash 3 times, and then wash with deionized water A 3 times, let stand, separate the liquids, take the organic phase, add anhydrous sodium sulfate to dry, filter, take the filtrate, distill under reduced pressure, and dry in a vacuum at 50°C to constant weight to obtain the intermediate product II. The usage ratio of intermediate product I, triethylamine and perfluorooctanoyl chloride is 1 mol: 1 mol: 1 mol; The usage ratio of intermediate product I and dichloromethane C is 1 mol:1660 mL; The dosage ratio of perfluorooctanoyl chloride to dichloromethane D is 1 mol:1300 mL; See also Figure 2 As shown, the infrared data of intermediate II are as follows: 3443 cm -1 :-OH disappears; 2550cm -1 :-SH exists; 1733 cm -1 :-C=O exists; 1350 cm -1 :-CF exists.

[0057] S3: N2 protection, add 5-formyluracil, allylamine, anhydrous magnesium sulfate, and dichloromethane E into a three-necked flask, stir at 20°C for 20 hours, filter, take the filtrate, distill under reduced pressure, and dry under vacuum at room temperature to obtain intermediate III; The dosage ratio of formyluracil, allylamine and anhydrous magnesium sulfate is 1 mol: 1 mol: 1 mol; The dosage ratio of 5-formyluracil to dichloromethane E is 1 mol:420 mL; See also Figure 3 As shown, the infrared data of intermediate III are as follows: 1555cm -1 : -NH- (amide) exists; 1676cm -1 :-C=O (keto group in pyrimidine ring) exists; 1612cm -1 :-C=C- (pyrimidine) exists; 1720 cm -1 、2870 cm -1 、2720cm -1:HC=O (aldehyde group) disappears; 1634cm -1 :-C=C-exists.

[0058] S4: Add intermediate product II, photoinitiator TPO-L, and dichloromethane F into a flask. Dissolve intermediate product III in dichloromethane G and place in a constant pressure dropping funnel. Stir magnetically and add dropwise at a uniform speed while placing 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 was completed, the reaction apparatus was removed and vacuum distilled to obtain the target product IV, i.e., raw material A1; The usage ratio of intermediate product II and intermediate product III is 1 mol:1 mol; The usage ratio of intermediate product II and dichloromethane F is 1 mol: 3000 mL; The usage ratio of intermediate III to dichloromethane G is 1 mol: 600 mL; The amount of photoinitiator TPO-L used is 1wt% of the total mass of the reactants in step S4.

[0059] See also Figure 4 As shown, the infrared data of A1 raw material is as follows: 2550cm -1 :-SH exists and weakens; 1733 cm -1 :-C=O (ester group) exists; 1350 cm -1 :-CF exists; 1555cm -1 : -NH- (amide) exists; 1676cm -1 :-C=O (keto group in pyrimidine ring) exists; 1612cm -1 :-C=C- (pyrimidine) exists; 1634cm -1 :-C=C- disappears.

[0060] Example 2 This embodiment provides a method for preparing an aqueous humor drainage device, comprising the following steps: Component A, component B and photoinitiator TPO-L were mixed, injected into a microfluidic mold, irradiated with ultraviolet light of a wavelength of 355 nm for 30 seconds, and placed in 37°C saline for oscillation for 7 days after curing to obtain a glaucoma aqueous humor drainage device.

[0061] The above-mentioned component A includes raw material A1 and raw material A2; the usage ratio of raw material A1 to raw material A2 is 0.01 mol:0.99 mol; The above-mentioned 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.

[0062] The above-mentioned B component includes B1 raw material and B2 raw material; the usage ratio of B1 raw material to B2 raw material is 2g:8g; The above-mentioned 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.

[0063] The usage ratio of the above-mentioned component A to component B is 1:0.97 based on the molar ratio of mercapto group to carbon-carbon double bond; the usage amount of the photoinitiator TPO-L is 0.5wt% of the total mass of the reactants.

[0064] The preparation method of the above-mentioned A1 raw material is as follows: S1: Add trimethylolpropane tris(3-mercaptopropionate), photoinitiator 2959, and dichloromethane A into a flask, dissolve undecenol in dichloromethane B and place in a constant pressure dropping funnel, stir magnetically, and place under a UV lamp with a wavelength of 355 nm and a light intensity of 400 mJ / cm 2 , irradiated for 10 min; after the reaction was completed, the reaction apparatus was removed and vacuum distillation was performed to obtain intermediate product I; The ratio of trimethylolpropane tris(3-mercaptopropionate) and undecenyl alcohol is 1 mol:1 mol; The dosage ratio of trimethylolpropane tris(3-mercaptopropionate) to dichloromethane A is 1 mol:1200 mL; The dosage ratio of undecenyl alcohol to dichloromethane B is 1 mol:510 mL; The amount of photoinitiator 2959 used is 1 wt % of the total mass of the reactants in step S1.

[0065] S2: Add the intermediate product I, triethylamine, and dichloromethane C into a flask and stir. Place perfluorooctanoyl chloride and dichloromethane D in a constant pressure dropping funnel, place in an ice bath, stir magnetically, and dropwise add at a uniform speed. Continue stirring for 12 hours after the addition is completed. Stop stirring, let stand, filter, take the filtrate, add 20wt% dilute hydrochloric acid solution to wash 3 times, add saturated sodium bicarbonate aqueous solution to wash 3 times, and then wash with deionized water A 3 times, let stand, separate the liquids, take the organic phase, add anhydrous sodium sulfate to dry, filter, take the filtrate, distill under reduced pressure, and dry in a vacuum at 50°C to constant weight to obtain the intermediate product II. The usage ratio of intermediate product I, triethylamine and perfluorooctanoyl chloride is 1 mol: 1 mol: 1 mol; The usage ratio of intermediate product I and dichloromethane C is 1 mol:1700 mL; The usage ratio of perfluorooctanoyl chloride and dichloromethane D is 1 mol:1300 mL.

[0066] S3: N2 protection, add 5-formyluracil, allylamine, anhydrous magnesium sulfate, and dichloromethane E into a three-necked flask, stir at 20°C for 20 hours, filter, take the filtrate, distill under reduced pressure, and dry under vacuum at room temperature to obtain intermediate III; The dosage ratio of 5-formyluracil, allylamine and anhydrous magnesium sulfate is 1 mol: 1 mol: 1 mol; The usage ratio of 5-formyluracil to dichloromethane E is 1 mol:420 mL.

[0067] S4: Add intermediate II, photoinitiator 2959, and dichloromethane F into a flask. Dissolve intermediate III in dichloromethane G and place in a constant pressure dropping funnel. Stir magnetically and place under a UV lamp while dropping at a constant speed. The wavelength is 355nm and the light intensity is 400mJ / cm 2 , irradiate for 10 minutes; after the reaction is completed, remove the reaction device and perform vacuum distillation to obtain the target product IV; The usage ratio of intermediate product II and intermediate product III is 1 mol:1 mol; The usage ratio of intermediate product II and dichloromethane F is 1 mol: 3000 mL; The usage ratio of intermediate III to dichloromethane G is 1 mol: 600 mL; The amount of photoinitiator 2959 used is 1wt% of the total mass of the reactants in step S4.

[0068] Example 3 This embodiment provides a method for preparing an aqueous humor drainage device, comprising the following steps: Component A, component B and photoinitiator 184 were mixed, injected into a microfluidic mold, irradiated with ultraviolet light of a wavelength of 355 nm for 30 seconds, and placed in 37° C. physiological saline for oscillation for 7 days after curing to obtain a glaucoma aqueous humor drainage device.

[0069] The above-mentioned component A includes raw material A1 and raw material A2; the usage ratio of raw material A1 to raw material A2 is 0.03 mol:0.97 mol; The above-mentioned 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.

[0070] The above-mentioned B component includes B1 raw material and B2 raw material; the usage ratio of B1 raw material to B2 raw material is 2g:8g; The above-mentioned 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.

[0071] The usage ratio of the above-mentioned component A to component B is 1:0.97 based on the molar ratio of mercapto group to carbon-carbon double bond; the usage amount of the photoinitiator 184 is 1wt% of the total mass of the reactants.

[0072] The preparation method of the above-mentioned A1 raw material is as follows: S1: Trimethylolpropane tris(3-mercaptopropionate), photoinitiator 184, and dichloromethane A were added to a flask, 5-hexenyl-1-ol was dissolved in dichloromethane B and placed in a constant pressure dropping funnel. The mixture was stirred magnetically and dropped at a constant speed under a UV lamp with a wavelength of 355 nm and a light intensity of 400 mJ / cm 2 , irradiated for 8 minutes; after the reaction was completed, the reaction device was removed and distilled under reduced pressure to obtain intermediate product I; The ratio of trimethylolpropane tris(3-mercaptopropionate) and 5-hexenyl-1-ol is 1 mol:1 mol; The dosage ratio of trimethylolpropane tris(3-mercaptopropionate) to dichloromethane A is 1 mol:1200 mL; The ratio of 5-hexenyl-1-ol to dichloromethane B is 1 mol:300 mL; The amount of photoinitiator 184 used is 1 wt % of the total mass of the reactants in step S1.

[0073] S2: Add the intermediate product I, triethylamine, and dichloromethane C into a flask and stir. Place perfluorooctanoyl chloride and dichloromethane D in a constant pressure dropping funnel, place in an ice bath, stir magnetically, and dropwise add at a uniform speed. Continue stirring for 10 hours after the addition is completed. Stop stirring, let stand, filter, take the filtrate, add 20wt% dilute hydrochloric acid solution to wash 3 times, add saturated sodium bicarbonate aqueous solution to wash 3 times, and then wash with deionized water A 3 times, let stand, separate the liquids, take the organic phase, add anhydrous sodium sulfate to dry, filter, take the filtrate, distill under reduced pressure, and dry in a vacuum at 50°C to constant weight to obtain the intermediate product II. The usage ratio of intermediate product I, triethylamine and perfluorooctanoyl chloride is 1 mol: 1 mol: 1 mol; The usage ratio of intermediate product I and dichloromethane C is 1 mol:1500 mL; The usage ratio of perfluorooctanoyl chloride and dichloromethane D is 1 mol:1300 mL.

[0074] S3: N2 protection, add 5-formyluracil, allylamine, anhydrous magnesium sulfate, and dichloromethane E into a three-necked flask, stir at 20°C for 20 hours, filter, take the filtrate, distill under reduced pressure, and dry under vacuum at room temperature to obtain intermediate III; The dosage ratio of 5-formyluracil, allylamine and anhydrous magnesium sulfate is 1 mol: 1 mol: 1 mol; The usage ratio of 5-formyluracil to dichloromethane E is 1 mol:420 mL.

[0075] S4: Add intermediate II, photoinitiator 184, and dichloromethane F into a flask. Dissolve intermediate III in dichloromethane G and place in a constant pressure dropping funnel. Stir magnetically and place under a UV lamp while dropping at a constant speed. The wavelength is 355 nm and the light intensity is 400 mJ / cm 2 , irradiated for 8 minutes; after the reaction was completed, the reaction device was removed and vacuum distillation was performed to obtain the target product IV, i.e., the A1 raw material; The usage ratio of intermediate product II and intermediate product III is 1 mol:1 mol; The usage ratio of intermediate product II and dichloromethane F is 1 mol: 2800 mL; The usage ratio of intermediate III to dichloromethane G is 1 mol: 600 mL; The amount of photoinitiator 184 used is 1 wt % of the total mass of the reactants in step S4.

[0076] Example 4 This embodiment provides a method for preparing an aqueous humor drainage device, comprising the following steps: Component A, component B and photoinitiator 2959 were mixed, injected into a microfluidic mold, irradiated with ultraviolet light of a wavelength of 355 nm for 30 seconds, and placed in 37° C. physiological saline for oscillation for 7 days after curing to obtain a glaucoma aqueous humor drainage device.

[0077] The above-mentioned component A includes raw material A1 and raw material A2; the usage ratio of raw material A1 to raw material A2 is 0.03 mol:0.97 mol; The above-mentioned A2 raw material is ethylene glycol bis(3-mercaptopropionate).

[0078] The above-mentioned B component includes B1 raw material and B2 raw material; the usage ratio of B1 raw material to B2 raw material is 2g:8g; The above-mentioned 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.

[0079] The usage ratio of the above-mentioned component A to component B is 1:0.97 based on the molar ratio of mercapto group to carbon-carbon double bond; the usage of the photoinitiator 2959 is 1wt% of the total mass of the reactants.

[0080] The preparation method of the above-mentioned A1 raw material is as follows: S1: Trimethylolpropane tris(3-mercaptopropionate), photoinitiator 2959, and dichloromethane A were added to a flask, 9-decene-1-ol was dissolved in dichloromethane B and placed in a constant pressure dropping funnel, stirred magnetically, and placed under a UV lamp with a wavelength of 355 nm and a light intensity of 400 mJ / cm 2 , irradiated for 10 min; after the reaction was completed, the reaction apparatus was removed and vacuum distillation was performed to obtain intermediate product I; The ratio of trimethylolpropane tris(3-mercaptopropionate) and 9-decen-1-ol is 1 mol:1 mol; The dosage ratio of trimethylolpropane tris(3-mercaptopropionate) to dichloromethane A is 1 mol:1200 mL; The dosage ratio of 9-decen-1-ol to dichloromethane B is 1 mol:450 mL; The amount of photoinitiator 2959 used is 1 wt % of the total mass of the reactants in step S1.

[0081] S2: Add the intermediate product I, triethylamine, and dichloromethane C into a flask and stir. Place heptafluorobutyryl chloride and dichloromethane D in a constant pressure dropping funnel, place in an ice bath, stir magnetically, and dropwise add at a uniform speed. Continue stirring for 10 hours after the addition is completed. Stop stirring, let stand, filter, take the filtrate, add 20wt% dilute hydrochloric acid solution to wash 3 times, add saturated sodium bicarbonate aqueous solution to wash 3 times, and then wash with deionized water A 3 times, let stand, separate the liquids, take the organic phase, add anhydrous sodium sulfate to dry, filter, take the filtrate, distill under reduced pressure, and dry in a vacuum at 50°C to constant weight to obtain the intermediate product II. The usage ratio of intermediate product I, triethylamine and heptafluorobutyryl chloride is 1 mol: 1 mol: 1 mol; The usage ratio of intermediate product I and dichloromethane C is 1 mol:1660 mL; The usage ratio of heptafluorobutyryl chloride to dichloromethane D is 1 mol:700 mL.

[0082] S3: N2 protection, add 5-formyluracil, allylamine, anhydrous magnesium sulfate, and dichloromethane E into a three-necked flask, stir at 20°C for 20 hours, filter, take the filtrate, distill under reduced pressure, and dry under vacuum at room temperature to obtain intermediate III; The dosage ratio of 5-formyluracil, allylamine and anhydrous magnesium sulfate is 1 mol: 1 mol: 1 mol; The usage ratio of 5-formyluracil to dichloromethane E is 1 mol:420 mL.

[0083] S4: Add intermediate II, photoinitiator 2959, and dichloromethane F into a flask. Dissolve intermediate III in dichloromethane G and place in a constant pressure dropping funnel. Stir magnetically and place under a UV lamp while dropping at a constant speed. The wavelength is 355nm and the light intensity is 400mJ / cm 2 , irradiated for 8 minutes; after the reaction was completed, the reaction device was removed and vacuum distillation was performed to obtain the target product IV, i.e., the A1 raw material; The usage ratio of intermediate product II and intermediate product III is 1 mol:1 mol; The usage ratio of intermediate product II and dichloromethane F is 1 mol: 2360 mL; The usage ratio of intermediate III to dichloromethane G is 1 mol: 600 mL; The amount of photoinitiator 2959 used is 1wt% of the total mass of the reactants in step S4.

[0084] Example 5 This embodiment provides a method for preparing an aqueous humor drainage device, comprising the following steps: Component A, component B and photoinitiator TPO-L were mixed, injected into a microfluidic mold, irradiated with ultraviolet light of a wavelength of 355 nm for 30 seconds, and placed in 37°C saline for oscillation for 7 days after curing to obtain a glaucoma aqueous humor drainage device.

[0085] The above-mentioned component A includes raw material A1 and raw material A2; the usage ratio of raw material A1 to raw material A2 is 0.04 mol:0.96 mol; The above-mentioned 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.

[0086] The above-mentioned B component includes B1 raw material and B2 raw material; the usage ratio of B1 raw material to B2 raw material is 2g:8g; The above B1 raw material is 2-phenylethyl methacrylate.

[0087] The usage ratio of the above-mentioned component A to component B is 1:0.97 based on the molar ratio of mercapto group to carbon-carbon double bond; the usage amount of the photoinitiator TPO-L is 0.5wt% of the total mass of the reactants.

[0088] The preparation method of the above-mentioned A1 raw material is as follows: S1: Trimethylolpropane tris(3-mercaptopropionate), photoinitiator TPO-L, and dichloromethane A were added to a flask, 9-decene-1-ol was dissolved in dichloromethane B and placed in a constant pressure dropping funnel, stirred magnetically, and 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 was completed, the reaction apparatus was removed and distilled under reduced pressure to obtain intermediate product I; The ratio of trimethylolpropane tris(3-mercaptopropionate) and 9-decen-1-ol is 1 mol:1 mol; The ratio of trimethylolpropane tris(3-mercaptopropionate) to dichloromethane A is 1 mol:1200 mL; the ratio of 9-decen-1-ol to dichloromethane B is 1 mol:450 mL; The amount of photoinitiator TPO-L used is 1wt% of the total mass of the reactants in step S1.

[0089] S2: Add the intermediate product I, triethylamine, and dichloromethane C into a flask and stir. Place heptafluorobutyryl chloride and dichloromethane D in a constant pressure dropping funnel, place in an ice bath, stir magnetically, and dropwise add at a uniform speed. Continue stirring for 10 hours after the addition is completed. Stop stirring, let stand, filter, take the filtrate, add 20wt% dilute hydrochloric acid solution to wash 3 times, add saturated sodium bicarbonate aqueous solution to wash 3 times, and then wash with deionized water A 3 times, let stand, separate the liquids, take the organic phase, add anhydrous sodium sulfate to dry, filter, take the filtrate, distill under reduced pressure, and dry in a vacuum at 50°C to constant weight to obtain the intermediate product II. The usage ratio of intermediate product I, triethylamine and heptafluorobutyryl chloride is 1 mol: 1 mol: 1 mol; The usage ratio of intermediate product I and dichloromethane C is 1 mol:1370 mL; The usage ratio of heptafluorobutyryl chloride to dichloromethane D is 1 mol:700 mL.

[0090] S3: N2 protection, add 5-formyluracil, allylamine, anhydrous magnesium sulfate, and dichloromethane E into a three-necked flask, stir at 20°C for 20 hours, filter, take the filtrate, distill under reduced pressure, and dry under vacuum at room temperature to obtain intermediate III; The dosage ratio of 5-formyluracil, allylamine and anhydrous magnesium sulfate is 1 mol: 1 mol: 1 mol; The usage ratio of 5-formyluracil to dichloromethane E is 1 mol:420 mL.

[0091] S4: Add intermediate product II, photoinitiator TPO-L, and dichloromethane F into a flask. Dissolve intermediate product III in dichloromethane G and place in a constant pressure dropping funnel. Stir magnetically and add dropwise at a uniform speed while placing 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 was completed, the reaction apparatus was removed and vacuum distilled to obtain the target product IV, i.e., raw material A1; The usage ratio of intermediate product II and intermediate product III is 1 mol:1 mol; The usage ratio of intermediate product II and dichloromethane F is 1 mol: 2070 mL; The usage ratio of intermediate III to dichloromethane G is 1 mol: 600 mL; The amount of photoinitiator TPO-L used is 1wt% of the total mass of the reactants in step S4.

[0092] Example 6 This embodiment provides a method for preparing an aqueous humor drainage device, comprising the following steps: Component A, component B and photoinitiator TPO-L were mixed, injected into a microfluidic mold, irradiated with ultraviolet light of a wavelength of 355 nm for 30 seconds, and placed in 37°C saline for oscillation for 7 days after curing to obtain a glaucoma aqueous humor drainage device.

[0093] The above-mentioned component A includes raw material A1 and raw material A2; the usage ratio of raw material A1 to raw material A2 is 0.05 mol:0.95 mol; The above-mentioned A2 raw material is a mixture of 3-mercapto-β, 4-dimethylcyclohexaneethanethiol and ethylene glycol bis(3-mercaptopropionate) in a molar ratio of 0.8:0.2.

[0094] The above-mentioned B component includes B1 raw material and B2 raw material; the usage ratio of B1 raw material to B2 raw material is 2g:8g; The above B1 raw material is a mixture of ethyl acrylate and 2-phenylethyl methacrylate in a mass ratio of 1.4:0.6.

[0095] The usage ratio of the above-mentioned component A to component B is 1:0.97 based on the molar ratio of mercapto group to carbon-carbon double bond; the usage amount of the photoinitiator TPO-L is 0.5wt% of the total mass of the reactants.

[0096] The preparation method of the above A1 raw material is as follows: S1: Add trimethylolpropane tris(3-mercaptopropionate), photoinitiator TPO-L, and dichloromethane A into a flask, dissolve undecenol in dichloromethane B and place in a constant pressure dropping funnel, stir magnetically, and place under a UV lamp with a wavelength of 355nm and a light intensity of 400mJ / cm 2 , irradiated for 5 min; after the reaction was completed, the reaction apparatus was removed and distilled under reduced pressure to obtain intermediate product I; The ratio of trimethylolpropane tris(3-mercaptopropionate) and undecenyl alcohol is 1 mol:1 mol; The ratio of trimethylolpropane tris(3-mercaptopropionate) to dichloromethane A is 1 mol:610 mL; The dosage ratio of undecenyl alcohol to dichloromethane B is 1 mol:510 mL; The amount of photoinitiator TPO-L used is 1wt% of the total mass of the reactants in step S1.

[0097] S2: Add the intermediate product I, triethylamine, and dichloromethane C into a flask and stir. Place heptafluorobutyryl chloride and dichloromethane D in a constant pressure dropping funnel, place in an ice bath, stir magnetically, and dropwise add at a uniform speed. Continue stirring for 12 hours after the addition is completed. Stop stirring, let stand, filter, take the filtrate, add 20wt% dilute hydrochloric acid solution to wash 3 times, add saturated sodium bicarbonate aqueous solution to wash 3 times, and then wash with deionized water A 3 times, let stand, separate the liquids, take the organic phase, add anhydrous sodium sulfate to dry, filter, take the filtrate, distill under reduced pressure, and dry in a vacuum at 50°C to constant weight to obtain the intermediate product II. The usage ratio of intermediate product I, triethylamine and heptafluorobutyryl chloride is 1 mol: 1 mol: 1 mol; The usage ratio of intermediate product I and dichloromethane C is 1 mol:1140 mL; The usage ratio of heptafluorobutyryl chloride to dichloromethane D is 1 mol:700 mL.

[0098] S3: N2 protection, add 5-formyluracil, allylamine, anhydrous magnesium sulfate, and dichloromethane E into a three-necked flask, stir at 20°C for 20 hours, filter, take the filtrate, distill under reduced pressure, and dry under vacuum at room temperature to obtain intermediate III; The dosage ratio of 5-formyluracil, allylamine and anhydrous magnesium sulfate is 1 mol: 1 mol: 1 mol; The usage ratio of 5-formyluracil to dichloromethane E is 1 mol:420 mL.

[0099] S4: Add intermediate product II, photoinitiator TPO-L, and dichloromethane F into a flask. Dissolve intermediate product III in dichloromethane G and place in a constant pressure dropping funnel. Stir magnetically and add dropwise at a uniform speed while placing 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 was completed, the reaction apparatus was removed and vacuum distilled to obtain the target product IV, i.e., raw material A1; The usage ratio of intermediate product II and intermediate product III is 1 mol:1 mol; The usage ratio of intermediate product II and dichloromethane F is 1 mol:1840 mL; The usage ratio of intermediate III to dichloromethane G is 1 mol: 600 mL; The amount of photoinitiator TPO-L used is 1wt% of the total mass of the reactants in step S4.

[0100] Example 7 This embodiment provides a method for preparing an aqueous humor drainage device, comprising the following steps: Component A, component B and photoinitiator 2959 were mixed, injected into a microfluidic mold, irradiated with ultraviolet light of a wavelength of 355 nm for 30 seconds, and placed in 37° C. physiological saline for oscillation for 7 days after curing to obtain a glaucoma aqueous humor drainage device.

[0101] The above-mentioned component A includes raw material A1 and raw material A2; the usage ratio of raw material A1 to raw material A2 is 0.02 mol:0.98 mol; 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.

[0102] The above-mentioned B component includes B1 raw material and B2 raw material; the usage ratio of B1 raw material to B2 raw material is 2g:8g; The above-mentioned B1 raw material is a mixture of triallyl isocyanurate and ethyl acrylate in a mass ratio of 0.8:1.2.

[0103] The usage ratio of the above-mentioned component A to component B is 1:0.95 based on the molar ratio of mercapto group to carbon-carbon double bond; the usage amount of the photoinitiator 2959 is 1.5wt% of the total mass of the reactants.

[0104] The preparation method of the above-mentioned A1 raw material is as follows: S1: Trimethylolpropane tris(3-mercaptopropionate), photoinitiator 184, and dichloromethane A were added to a flask, 9-decene-1-ol was dissolved in dichloromethane B and placed in a constant pressure dropping funnel, stirred magnetically, and placed under a UV lamp with a wavelength of 355 nm and a light intensity of 400 mJ / cm 2 , irradiated for 10 min; after the reaction was completed, the reaction apparatus was removed and vacuum distillation was performed to obtain intermediate product I; The ratio of trimethylolpropane tris(3-mercaptopropionate) and 9-decen-1-ol is 1 mol:1 mol; The dosage ratio of trimethylolpropane tris(3-mercaptopropionate) to dichloromethane A is 1 mol:1200 mL; The dosage ratio of 9-decen-1-ol to dichloromethane B is 1 mol:450 mL; The amount of photoinitiator 184 used is 1 wt % of the total mass of the reactants in step S1.

[0105] S2: Add the intermediate product I, triethylamine, and dichloromethane C into a flask and stir. Place perfluorooctanoyl chloride and dichloromethane D in a constant pressure dropping funnel, place in an ice bath, stir magnetically, and dropwise add at a uniform speed. Continue stirring for 8 hours after the addition is completed. Stop stirring, let stand, filter, take the filtrate, add 20wt% dilute hydrochloric acid solution to wash 3 times, add saturated sodium bicarbonate aqueous solution to wash 3 times, and then wash with deionized water A 3 times, let stand, separate the liquids, take the organic phase, add anhydrous sodium sulfate to dry, filter, take the filtrate, distill under reduced pressure, and dry in a vacuum at 50°C to constant weight to obtain the intermediate product II. The usage ratio of intermediate product I, triethylamine and perfluorooctanoyl chloride is 1 mol: 1 mol: 1 mol; The usage ratio of intermediate product I and dichloromethane C is 1 mol:1080 mL; The usage ratio of perfluorooctanoyl chloride and dichloromethane D is 1 mol:1300 mL.

[0106] S3: N2 protection, add 5-formyluracil, allylamine, anhydrous magnesium sulfate, and dichloromethane E into a three-necked flask, stir at 20°C for 20 hours, filter, take the filtrate, distill under reduced pressure, and dry under vacuum at room temperature to obtain intermediate III; The dosage ratio of 5-formyluracil, allylamine and anhydrous magnesium sulfate is 1 mol: 1 mol: 1 mol; The usage ratio of 5-formyluracil to dichloromethane E is 1 mol:420 mL.

[0107] S4: Add intermediate II, photoinitiator 184, and dichloromethane F into a flask. Dissolve intermediate III in dichloromethane G and place in a constant pressure dropping funnel. Stir magnetically and place under a UV lamp while dropping at a constant speed. The wavelength is 355 nm and the light intensity is 400 mJ / cm 2 , irradiated for 8 minutes; after the reaction was completed, the reaction device was removed and vacuum distillation was performed to obtain the target product IV, i.e., the A1 raw material; The usage ratio of intermediate product II and intermediate product III is 1 mol:1 mol; The usage ratio of intermediate product II and dichloromethane F is 1 mol: 2380 mL; The usage ratio of intermediate III to dichloromethane G is 1 mol: 600 mL; The amount of photoinitiator 184 used is 1 wt % of the total mass of the reactants in step S4.

[0108] Example 8 This embodiment provides a method for preparing an aqueous humor drainage device, comprising the following steps: Component A, component B and photoinitiator 184 were mixed, injected into a microfluidic mold, irradiated with ultraviolet light of a wavelength of 355 nm for 30 seconds, and placed in 37° C. physiological saline for oscillation for 7 days after curing to obtain a glaucoma aqueous humor drainage device.

[0109] The above-mentioned component A includes raw material A1 and raw material A2; the usage ratio of raw material A1 to raw material A2 is 0.02 mol:0.98 mol; The above-mentioned A2 raw material is ethylene glycol bis(3-mercaptopropionate).

[0110] The above-mentioned B component includes B1 raw material and B2 raw material; the usage ratio of B1 raw material to B2 raw material is 2g:8g; The above B1 raw material is 2-phenylethyl methacrylate.

[0111] The usage ratio of the above-mentioned component A to component B is 1:0.99 in terms of the molar ratio of mercapto group to carbon-carbon double bond; the usage amount of the photoinitiator 184 is 1wt% of the total mass of the reactants.

[0112] The preparation method of the above-mentioned A1 raw material is as follows: S1: Trimethylolpropane tris(3-mercaptopropionate), photoinitiator 184, and dichloromethane A were added to a flask, 9-decene-1-ol was dissolved in dichloromethane B and placed in a constant pressure dropping funnel, stirred magnetically, and 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 was completed, the reaction apparatus was removed and distilled under reduced pressure to obtain intermediate product I; The ratio of trimethylolpropane tris(3-mercaptopropionate) and 9-decen-1-ol is 1 mol:1 mol; The ratio of trimethylolpropane tris(3-mercaptopropionate) to dichloromethane A is 1 mol:710 mL; The dosage ratio of 9-decen-1-ol to dichloromethane B is 1 mol:450 mL; The amount of photoinitiator 184 used is 1 wt % of the total mass of the reactants in step S1.

[0113] S2: Add the intermediate product I, triethylamine, and dichloromethane C into a flask and stir. Place perfluorooctanoyl chloride and dichloromethane D in a constant pressure dropping funnel, place in an ice bath, stir magnetically, and dropwise add at a uniform speed. Continue stirring for 8 hours after the addition is completed. Stop stirring, let stand, filter, take the filtrate, add 20wt% dilute hydrochloric acid solution to wash 3 times, add saturated sodium bicarbonate aqueous solution to wash 3 times, and then wash with deionized water A 3 times, let stand, separate the liquids, take the organic phase, add anhydrous sodium sulfate to dry, filter, take the filtrate, distill under reduced pressure, and dry in a vacuum at 50°C to constant weight to obtain the intermediate product II. The usage ratio of intermediate product I, triethylamine and perfluorooctanoyl chloride is 1 mol: 1 mol: 1 mol; The usage ratio of intermediate product I and dichloromethane C is 1 mol:1180 mL; The usage ratio of perfluorooctanoyl chloride and dichloromethane D is 1 mol:1300 mL.

[0114] S3: N2 protection, add 5-formyluracil, allylamine, anhydrous magnesium sulfate, and dichloromethane E into a three-necked flask, stir at 20°C for 20 hours, filter, take the filtrate, distill under reduced pressure, and dry under vacuum at room temperature to obtain intermediate III; The dosage ratio of 5-formyluracil, allylamine and anhydrous magnesium sulfate is 1 mol: 1 mol: 1 mol; The usage ratio of 5-formyluracil to dichloromethane E is 1 mol:420 mL.

[0115] S4: Add intermediate II, photoinitiator 184, and dichloromethane F into a flask. Dissolve intermediate III in dichloromethane G and place in a constant pressure dropping funnel. Stir magnetically and place under a UV lamp while dropping at a constant speed. The wavelength is 355 nm and the light intensity is 400 mJ / cm 2 , irradiated for 10 min; after the reaction was completed, the reaction device was removed and vacuum distillation was performed to obtain the target product IV, i.e., raw material A1; The usage ratio of intermediate product II and intermediate product III is 1 mol:1 mol; The usage ratio of intermediate product II and dichloromethane F is 1 mol: 2480 mL; The usage ratio of intermediate III to dichloromethane G is 1 mol: 600 mL; The amount of photoinitiator 184 used is 1 wt % of the total mass of the reactants in step S4.

[0116] The aqueous humor drainage devices provided in the following comparative examples of the present invention are compared with Example 1: Comparative Example 1 The difference between this comparative example and Example 1 is that the usage ratio of component A to component B is 1:1.2 in terms of the molar ratio of mercapto group to carbon-carbon double bond.

[0117] Comparative Example 2 The difference between this comparative example and Example 1 is that the usage ratio of component A to component B is 1:0.8 in terms of the molar ratio of mercapto group to carbon-carbon double bond.

[0118] Comparative Example 3 The difference between this comparative example and Example 1 is that component A only includes raw material A2.

[0119] Comparative Example 4 The difference between this comparative example and Example 1 is that the usage ratio of raw material A1 to raw material A2 is 0.1 mol:0.9 mol.

[0120] Comparative Example 5 The difference between this comparative example and Example 1 is that component B only includes B2 raw material.

[0121] Comparative Example 6 The difference between this comparative example and Example 1 is that the usage ratio of B1 raw material to B2 raw material is 4g:6g.

[0122] Comparative Example 7 The difference between this comparative example and Example 1 is that the B2 raw material is gelatin, that is, the gelatin is not modified.

[0123] Comparative Example 8 The difference between this comparative example and Example 1 is that the raw material A1 is 5-formyluracil.

[0124] Comparative Example 9 The difference between this comparative example and Example 1 is that the preparation method of raw material A1 is as follows: S1: N2 protection, add 5-formyluracil, allylamine, anhydrous magnesium sulfate, and dichloromethane E into a three-necked flask, stir at 20°C for 20 hours, filter, take the filtrate, distill under reduced pressure, and dry under vacuum at room temperature to obtain intermediate I; The dosage ratio of 5-formyluracil, allylamine and anhydrous magnesium sulfate is 1 mol: 1 mol: 1 mol; The usage ratio of 5-formyluracil to dichloromethane E is 1 mol:420 mL.

[0125] S2: Trimethylolpropane tris(3-mercaptopropionate), photoinitiator TPO-L, and dichloromethane F were added to the flask. The intermediate product I was dissolved in dichloromethane G and placed in a constant pressure dropping funnel. The funnel was stirred magnetically and placed under a UV lamp with a wavelength of 355 nm and a light intensity of 400 mJ / cm. 2 , irradiate for 5 minutes; after the reaction is completed, remove the reaction device and perform vacuum distillation to obtain the target product; The ratio of trimethylolpropane tris(3-mercaptopropionate) and intermediate product I is 1 mol:1 mol; The ratio of trimethylolpropane tris(3-mercaptopropionate) to dichloromethane F is 1 mol:1200 mL; The usage ratio of intermediate product I and dichloromethane G is 1 mol:1660 mL; The amount of photoinitiator TPO-L used is 1wt% of the total mass of the reactants in step S2.

[0126] Comparative Example 10 The difference between this comparative example and Example 1 is that the preparation method of raw material A1 is as follows: S1: Trimethylolpropane tris(3-mercaptopropionate), photoinitiator TPO-L, and dichloromethane A were added to a flask, 9-decene-1-ol was dissolved in dichloromethane B and placed in a constant pressure dropping funnel, stirred magnetically, and 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 was completed, the reaction apparatus was removed and distilled under reduced pressure to obtain intermediate product I; The ratio of trimethylolpropane tris(3-mercaptopropionate) and 9-decen-1-ol is 1 mol:1 mol; The dosage ratio of trimethylolpropane tris(3-mercaptopropionate) to dichloromethane A is 1 mol:1200 mL; The dosage ratio of 9-decen-1-ol to dichloromethane B is 1 mol:450 mL; The amount of photoinitiator TPO-L used is 1wt% of the total mass of the reactants in step S1.

[0127] S2: Add the intermediate product I, triethylamine, and dichloromethane C into a flask and stir. Place perfluorooctanoyl chloride and dichloromethane D in a constant pressure dropping funnel, place in an ice bath, stir magnetically, and dropwise add at a uniform speed. Continue stirring for 8 hours after the addition is completed. Stop stirring, let stand, filter, take the filtrate, add 20wt% dilute hydrochloric acid solution to wash 3 times, add saturated sodium bicarbonate aqueous solution to wash 3 times, and then wash with deionized water A 3 times, let stand, separate the liquids, take the organic phase, add anhydrous sodium sulfate to dry, filter, take the filtrate, distill under reduced pressure, and dry in a vacuum at 50°C to constant weight to obtain the target product. The usage ratio of intermediate product I, triethylamine and perfluorooctanoyl chloride is 1 mol: 1 mol: 1 mol; The usage ratio of intermediate product I and dichloromethane C is 1 mol:1660 mL; The usage ratio of perfluorooctanoyl chloride and dichloromethane D is 1 mol:1300 mL.

[0128] The performance of the aqueous humor drainage devices prepared in the embodiments of the present invention and the comparative examples were measured respectively, and the test method was as follows: (1) Cell inhibition effect test: To evaluate the effect of cell inhibition by cell response, primary fibroblasts (10 cells / well) were cultured in DMEM containing 10% fetal bovine serum. After the fibroblasts were precipitated, the migration assay was performed by inserting a glaucoma drainage tube so that it was completely immersed in the medium. After 5 days of culture, the status 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.

[0129] (2) 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. Six samples of each coverlay (36 samples in total) were placed in 6-well tissue culture plates and irradiated under UV light for 10-15 min. Cells were seeded onto the coverslips at a density of approximately 11 000 cells / cm. 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 was determined for each sample group and statistical comparisons of viability assays were performed as described above.

[0130] (3) Water contact angle: The raw materials in the examples were injected into films according to the proportions, and the test was performed according to GB / T 30693-2014.

[0131] (4) Monomer residue test: Use gas chromatography to test. Monomer residue expression method: <1ppm is recorded as "OK"; >1ppm is recorded as "NG".

[0132] (5) Mechanical strength test: Fold the drainage tube in half and observe whether there are cracks or creases. The mechanical strength is expressed as follows: no cracks and no creases are marked as "○", no cracks and creases are marked as "◎", and cracks and creases are marked as "●".

[0133] (6) Elastic modulus test: The raw materials in the example were injected into a 5B dumbbell-shaped mold according to the proportions and cured, and the test was performed with reference to GB / T 1040.3-2006.

[0134] (7) Drainage efficiency test: 10 ml of deionized water is passed through the drainage tube at a constant flow rate (64 μl / min), and the time required for the deionized water to flow completely is recorded to determine the drainage efficiency.

[0135] The test results are shown in Table 1: .

[0136] First, it can be seen from Examples 1-8 and Comparative Examples 1-10 in Table 1 that the aqueous humor drainage devices prepared in each embodiment of the present invention have excellent anti-cell proliferation and anti-cell adhesion properties, and at the same time have suitable water contact angles (hydrophilicity) and drainage efficiency, excellent mechanical properties, and extremely low monomer residues.

[0137] Second, it can be observed from Example 1 and Comparative Examples 1-2 that the reaction ratio of the thiol group and the carbon-carbon double bond is adjusted, and an excess of any component will lead to poor mechanical properties of the prepared drainage tube.

[0138] Third, it can be observed from Example 1 and Comparative Examples 3-4 that insufficient functional raw material A1 in component A will lead to the loss of anti-cell proliferation and anti-cell adhesion properties; excessive amount will lead to poor hydrophilicity.

[0139] Fourth, it can be observed from Example 1 and Comparative Examples 5-7 that the unreasonable amount of B1 raw material in component B will lead to the deterioration of mechanical properties; unmodified gelatin is used as a filler, the crosslinking density of the thiol and olefin materials is too large, it is difficult to form, and the drainage tube cannot be prepared.

[0140] Fifth, it can be observed from Example 1 and Comparative Examples 8-10 that adding only 5-formyl uracil will lead to poor anti-cell adhesion and excessive monomer residue; adding only thiol-modified 5-formyl uracil will also have the problem of poor anti-cell adhesion and the risk of drainage tube blockage; and adding only thiol-modified fluorine-containing structure will have the problem of insufficient anti-cell proliferation, the live / dead ratio of HTFs fibroblasts will increase after 5 days, and the risk of scarring will increase.

[0141] 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

1. A photocurable material, characterized in that: It consists of component A, component B and photoinitiator I; The A component includes A1 raw material and A2 raw material; The A1 raw material contains antimetabolism structure, F element and thiol group at the same time; The A2 raw material is a thiol-containing compound; The B component includes 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; The B2 raw material is modified gelatin; The A1 raw material is prepared as follows: S1: Mix trimethylolpropane tris(3-mercaptopropionate), photoinitiator II, and dichloromethane A to obtain a mixed solution I; dissolve unsaturated alcohol in dichloromethane B to obtain a mixed solution II; under UV light irradiation, dropwise add the mixed solution II to the mixed solution I to react; after the reaction is completed, perform vacuum distillation to obtain an intermediate product I; S2: Mix the intermediate product I, triethylamine and dichloromethane C to obtain a mixed solution III; mix perfluoroalkyl acyl chloride and dichloromethane D under ice bath conditions to obtain a mixed solution IV; dropwise add the mixed solution IV to the mixed solution III, stir, react, let stand, filter, take the filtrate, and wash; The mixture was allowed to stand, separated, the organic phase was taken, dried, filtered, the filtrate was taken, distilled under reduced pressure, and dried in vacuum to constant weight to obtain intermediate product II; S3: Under inert gas protection, 5-formyluracil, allylamine, anhydrous magnesium sulfate and dichloromethane E are mixed, stirred at 20°C, filtered, and the filtrate is distilled under reduced pressure and dried under vacuum at room temperature to obtain intermediate III; S4: Mix the intermediate product II, photoinitiator III and dichloromethane F to obtain a mixed solution V; dissolve the intermediate product III in dichloromethane G to obtain a mixed solution VI; add the mixed solution VI dropwise to the mixed solution V under UV lamp irradiation to react; after the reaction is completed, perform reduced pressure distillation to obtain the A1 raw material.

2. The photocurable material according to claim 1, wherein: The anti-metabolism structure is a thymine structure.

3. The photocurable material according to claim 1, wherein: The unsaturated alcohol is selected from at least one of 9-decen-1-ol, undecenyl alcohol and 5-hexenyl-1-ol.

4. The photocurable material according to claim 1, wherein: The perfluoroalkyl acyl chloride is selected from at least one of heptafluorobutyryl chloride and perfluorooctanoyl chloride.

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

6. The photocurable material according to claim 1, wherein: In step S2, the molar ratio of the intermediate product I, the triethylamine, and the perfluoroalkyl acyl chloride is 1:(0.8-1.2):(0.8-1.2).

7. The photocurable material according to claim 1, wherein: In step S3, the molar ratio of the 5-formyluracil, the allylamine, and the anhydrous magnesium sulfate is 1:(0.8-1.2):(0.8-1.2).

8. The photocurable material according to claim 1, wherein: The molar ratio of the intermediate product II to 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.

9. The photocurable material according to any one of claims 1 to 8, characterized in that: 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 tris(3-mercaptopropionate).

10. The photocurable material according to any one of claims 1 to 8, characterized in that: 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).

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

4.

12. The photocurable material according to any one of claims 1 to 8, characterized in that: The usage ratio of the component A to the component B is 1:(0.95-0.99) based on the molar ratio of the mercapto group to the carbon-carbon double bond.

13. The photocurable material according to any one of claims 1 to 8, characterized in that: The amount of the photoinitiator I is 0.5-1.5wt% of the total mass of the reactants.

14. An aqueous humor drainage device, characterized in that: The photocurable material is prepared by a photocuring method according to any one of claims 1 to 13.

15. A method for preparing the aqueous humor drainage device according to claim 14, characterized in that: The method comprises the following steps: injecting a light-curing material into a microfluidic mold, irradiating the mold with ultraviolet light, and placing the mold in 37°C physiological saline for oscillation after curing to obtain an aqueous humor drainage device.

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