Drainage tube for treating glaucoma and preparation method thereof

Abstract

The present invention relates to the technical field of medical devices, and in particular to a drainage tube for treating glaucoma and a preparation method thereof. The drainage tube has a tubular structure and is prepared by aldehyde-amine condensation cross-linking reaction of component A and component B; the component A is a substance containing multiple amino groups; the component B is a dialdehyde structure; and the multiple amino substances include an amino-containing polymer matrix and a uracil-based macromolecule. The drainage tube for treating glaucoma provided by the present invention is based on gelatin, and homemade uracil-based macromolecules are added to the aldehyde-amine condensation cross-linking to form; on the one hand, the cross-linking reaction of the amino group and the aldehyde group is a controllable reaction, and the product is highly designable; on the other hand, the prepared drainage tube for treating glaucoma has no small molecule residues, and has good anti-fibroblast proliferation effect and anti-cell adhesion performance, and has a good drainage and filtration effect; and the preparation raw materials are easily available substances, which have the advantages of safety and non-toxicity.

Description

Technical Field

[0001] The present invention relates to the technical field of medical devices, and in particular to a drainage tube for treating glaucoma and a preparation method thereof. Background Art

[0002] Glaucoma is a type of optic nerve damage caused by pathologically high intraocular pressure. Controlling intraocular pressure has become the main means of treating glaucoma. Clinically, most glaucoma diseases can be treated by drainage device implantation, which can achieve the effect of lowering intraocular pressure and achieving controlled treatment of glaucoma.

[0003] A glaucoma drainage tube is a tubular structure that can be minimally invasively implanted, with an outer diameter of only 100-900 μm and an inner diameter of 10-100 μm. It is usually very small, soft and elastic, and can drain the aqueous humor out of the eye. Existing drainage tubes are mostly made of natural polymer materials.

[0004] However, when drainage tubes made of natural polymer materials are implanted in the body for a long time, they are prone to blockage by postoperative fibroblast proliferation, leading to failure of the drainage tubes. Summary of the invention

[0005] The purpose of the present invention is to provide a drainage tube for treating glaucoma, aiming at the problem that the drainage tube for treating glaucoma in the prior art becomes ineffective due to fibroblast proliferation blocking the drainage tube during long-term use. The drainage tube is prepared by aldehyde amine condensation; the material contains a uracil structure, which can prevent cell division and has an excellent anti-metabolic effect. At the same time, it has a certain molecular weight and can be enriched at the interface, and finally bonded to the main structure through a chemical reaction, which is safe and non-toxic.

[0006] The technical solution adopted by the present invention to solve its technical problem is:

[0007] A drainage tube for treating glaucoma, which has a tubular structure;

[0008] The drainage tube for treating glaucoma is prepared by aldehyde-amine condensation cross-linking reaction of component A and component B;

[0009] The component A is a substance containing multiple amino groups;

[0010] The B component is a dialdehyde structure; and

[0011] The polyamino substance includes an amino-containing polymer matrix and uracil-based macromolecules;

[0012] The uracil-based macromolecule is prepared as follows:

[0013] S11, performing a ring-opening reaction on an epoxy ring-opening agent containing a uracil structure and an epoxy group containing an acryloxy group to obtain an intermediate product I;

[0014] S12, subjecting a vinyl silane coupling agent, an unsaturated quaternary ammonium salt, and acrylamide to a free radical polymerization reaction to obtain an intermediate product II;

[0015] S13, subjecting the intermediate product I to a hydrolysis-coupling reaction with the intermediate product II to obtain an intermediate product III;

[0016] S14, subjecting the intermediate product III and the polyamino structure to Michael addition reaction to obtain a uracil-based macromolecule.

[0017] Optionally, the epoxy ring-opening agent containing a uracil structure is an amino-containing uracil or a carboxyl-containing uracil.

[0018] Optionally, the amino-containing uracil is 4-aminouracil.

[0019] Optionally, the carboxyl-containing uracil is orotic acid.

[0020] Optionally, the epoxy containing acryloxy group is selected from at least one of glycidyl methacrylate and (glycidyloxy)ethyl methacrylate.

[0021] Optionally, in step S11, the epoxy ring-opening agent containing a uracil structure and the epoxy containing an acryloxy group are added at a molar ratio of 1:1 between the epoxy ring-opening agent and the epoxy group.

[0022] Optionally, the unsaturated quaternary ammonium salt is methacryloyloxyethyltrimethylammonium chloride.

[0023] Optionally, in step S12, the molar ratio of the vinyl silane coupling agent, the unsaturated quaternary ammonium salt, and the acrylamide is (0.2-0.4): (0.2-0.3): (0.3-0.6).

[0024] Optionally, the number of amino functional groups of the polyamino structure in step S14 is ≥2.

[0025] Optionally, in the polyamino substance, the mass ratio of the amino-containing polymer matrix to the uracil-based macromolecule is 100:(3-5).

[0026] Optionally, the dialdehyde structure is a straight-chain fatty aldehyde, and the number of carbon atoms of the straight-chain fatty aldehyde is 4-8.

[0027] Another object of the present invention is to provide a method for preparing the drainage tube for treating glaucoma as described above, comprising the following steps:

[0028] S1, dissolve component A according to the formula, remove bubbles, add it into the mold, let it stand for 6-10 hours, and cool it to obtain a primary drainage tube;

[0029] S2, preparing the organic solution of component B according to the formula amount;

[0030] S3, placing the primary drainage tube in the organic solution of component B according to the formula amount, and oscillating the reaction to obtain a cross-linked drainage tube;

[0031] S4, washing the cross-linked drainage tube with alkali, performing oscillation dialysis, and storing it at low temperature to obtain a drainage tube for treating glaucoma.

[0032] The beneficial effects of the present invention are:

[0033] The drainage tube for treating glaucoma provided by the present invention is mainly composed of gelatin, and is formed by adding homemade uracil-based macromolecules and aldehyde-based structures to form aldehyde-amine condensation cross-linking. On the one hand, the cross-linking reaction between the amino group and the aldehyde group is a controllable reaction, and the product has strong designability. On the other hand, the prepared drainage tube for treating glaucoma has no small molecule residues, and has good anti-fibroblast proliferation effect and anti-cell adhesion performance, and has good drainage and filtration effect. The raw materials for preparation are easy to obtain, and have the advantages of strong operability, safety and non-toxicity. BRIEF DESCRIPTION OF THE DRAWINGS

[0034] The present invention is further described below in conjunction with the accompanying drawings and embodiments.

[0035] Figure 1 is the infrared spectrum of the intermediate product I in Example 1 of the present invention;

[0036] Figure 2 is the infrared spectrum of the intermediate product II in Example 1 of the present invention;

[0037] Figure 3 is the infrared spectrum of the intermediate product III in Example 1 of the present invention;

[0038] Figure 4 This is the infrared spectrum of the uracil-based macromolecule in Example 1 of the present invention. DETAILED DESCRIPTION

[0039] 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.

[0040] The drainage tube is implanted in the body for a long time. In addition to the postoperative fibroblast proliferation that will block the drainage tube, the cells in the tissue fluid will also adhere to the drainage tube, which will eventually lead to poor filtration effect and failure of the drainage tube. In addition, the raw materials are required to be safe, non-toxic, and non-allergic; the release of small molecules in synthetic materials must be strictly controlled. At present, two methods are usually adopted to solve the problem of small molecule release in synthetic materials, both of which aim to convert small molecules into macromolecules. One is to use reactive functional small molecules to solidify simultaneously during the material molding process, but there are also small molecules that cannot fully react and remain, and the unreacted small molecules are removed during the soaking and dialysis process. This method has a large demand for reactive small molecules and has a large waste of cost. Another method is to first polymerize the reactive functional small molecules to form macromolecules, then blend them with the matrix, and finally solidify them. There are very few residual small molecules in this method, but there will be functional structures and matrix chain entanglements that cannot be effectively exerted.

[0041] On the other hand, gelatin is a water-soluble protein obtained by partial degradation of collagen in animal skin, bones and other connective tissues, and there are still a lot of residual amino groups. It is widely used in the medical field due to its biodegradability, good biocompatibility and film-forming properties. The preparation of drainage tubes by cross-linking gelatin and aldehyde groups through aldehyde-amine condensation also has unique advantages, but there are also problems such as postoperative cell proliferation and cell adhesion affecting drainage efficiency.

[0042] Based on this, in order to solve the problem in the prior art that drainage tubes for treating glaucoma become ineffective due to fibroblast proliferation blocking the drainage tubes during long-term use, the present invention provides a drainage tube for treating glaucoma, which has a tubular structure; the drainage tube for treating glaucoma is prepared from component A and component B through an aldehyde-amine condensation cross-linking reaction; specifically, component A is a polyamino-containing substance; component B is a dialdehyde structure; and the polyamino substance includes an amino-containing polymer matrix and a uracil-based macromolecule, specifically, the amino-containing polymer matrix preferably includes gelatin, and may also include at least one of chitosan and polyamino acid; and further preferably, chitosan and / or polyamino acid are 0-10wt% of the amino-containing polymer matrix; wherein 0wt% means no chitosan and / or polyamino acid is added.

[0043] The preferred uracil-based macromolecule of the present invention is prepared according to the following method:

[0044] S11, performing a ring-opening reaction on an epoxy ring-opening agent containing a uracil structure and an epoxy group containing an acryloxy group to obtain an intermediate product I;

[0045] S12, subjecting a vinyl silane coupling agent, an unsaturated quaternary ammonium salt, and acrylamide to a free radical polymerization reaction to obtain an intermediate product II;

[0046] S13, subjecting the intermediate product I to a hydrolysis-coupling reaction with the intermediate product II to obtain an intermediate product III;

[0047] S14, subjecting the intermediate III and the polyamino structure to Michael addition reaction to obtain a uracil-based macromolecule.

[0048] The preparation process of the uracil-based macromolecule is as follows. It should be noted that this preparation process is only for reference and does not constitute a limitation of the present invention:

[0049] ;

[0050] Where x, y, and z are all natural numbers greater than 1.

[0051] The uracil-based macromolecule is one of the raw materials for the drainage tube for the treatment of glaucoma. It contains uracil, silane, quaternary ammonium salt, amino and amide structures at the same time. First, the uracil structure can prevent cell division and has excellent anti-metabolic effect, which can reduce scarring of the surgical site after surgery and improve the drainage and filtration effect. Second, the silane structure has low atomic surface energy, which can reduce cell adhesion on the one hand and make the macromolecule migrate to the interface and accumulate on the interface (inner wall and outer wall) on the other hand, further improving the drainage and filtration effect. In addition, silane is a flexible chain structure with certain flexibility. toughness; third, the quaternary ammonium salt structure is a broad-spectrum antibacterial structure with excellent broad-spectrum antibacterial properties; fourth, the amino group can be used as a reaction site to react with the aldehyde cross-linking agent and bonded to the system to further fix the size of the drainage tube and improve safety and reliability; fifth, the amide group and quaternary ammonium salt have excellent hydrophilicity, which can compensate for the water repellency of the silane structure and improve the drainage and filtration performance; sixth, the macromolecular structure is a multi-amino, amide group and other structures, and its molecular structure is similar to gelatin. During the migration process, it has a certain chain entanglement with the main resin to form a uniform transition layer to avoid material performance defects.

[0052] The drainage tube for treating glaucoma provided by the present invention is mainly composed of gelatin, and is formed by adding homemade uracil-based macromolecules and aldehyde-based structures to form aldehyde-amine condensation cross-linking. On the one hand, the cross-linking reaction between the amino group and the aldehyde group is a controllable reaction, and the product has strong designability. On the other hand, the prepared drainage tube for treating glaucoma has no small molecule residues, and has good anti-fibroblast proliferation effect and anti-cell adhesion performance, and has good drainage and filtration effect. The raw materials for preparation are easy to obtain, and have the advantages of strong operability, safety and non-toxicity.

[0053] Specifically, the epoxy ring-opening agent in step S11 of the present invention is preferably an amino or carboxyl structure, that is, the epoxy ring-opening agent containing a uracil structure is an amino-containing uracil or a carboxyl-containing uracil; further, the present invention preferably uses an amino-containing uracil as 4-aminouracil; and preferably uses a carboxyl-containing uracil as orotic acid.

[0054] In the preferred embodiment of the present invention, the epoxy containing acryloxy group in step S11 is selected from at least one of glycidyl methacrylate and (glycidyloxy)ethyl methacrylate.

[0055] In order to take into account both the performance and economy of the drainage tube for treating glaucoma, the present invention preferably adds the epoxy ring-opener containing uracil structure and the epoxy containing acryloxy group in step S11 at a molar ratio of 1:1 between the epoxy ring-opener and the epoxy group.

[0056] Specifically, step S11 can be performed according to the following process:

[0057] S11, protected from light, add the epoxy ring-opener containing uracil structure, epoxy containing acryloyloxy group and hydroquinone to tetrahydrofuran, react at 25-70°C for 6-24h, cool to room temperature, add deionized water A, shake, add ethyl acetate for extraction, take the organic phase, dry with anhydrous sodium sulfate A, filter, take the filtrate, distill under reduced pressure, and dry in vacuo at 40°C for 12h to obtain intermediate product I.

[0058] The present invention preferably adds the epoxy ring-opener containing uracil structure, epoxy containing acryloxy group, tetrahydrofuran, deionized water A, ethyl acetate, and anhydrous sodium sulfate A in a ratio of 0.1 mol: 0.1 mol: 200 mL: 300 mL: 600 mL: 5 g; the amount of hydroquinone used is 0.1 wt% of the mass of epoxy containing acryloxy group.

[0059] In this step, both the amino ring-opener and the carboxyl ring-opener, i.e., the amino-containing uracil and the carboxyl-containing uracil, can undergo a ring-opening reaction with the epoxy group, but the reaction conditions are slightly different; the amino ring-opener can generally be carried out at room temperature, with or without the addition of a catalyst; the carboxyl ring-opener generally requires the addition of a catalyst (preferably tetrabutylammonium bromide as a catalyst) and requires a certain temperature. Another raw material for the above reaction is an epoxy containing an acryloxy group. When using an amino ring-opener, the amino group may simultaneously undergo a ring-opening reaction with the epoxy group and a Michael addition reaction with the acryloxy group. However, the epoxy ring-opening reaction is more active, and under the same conditions, the amino group preferentially undergoes a ring-opening reaction with the epoxy group.

[0060] In the preferred embodiment of the present invention, the vinyl silane coupling agent in step S12 is selected from at least one of KH151, KH171, and KH172; and preferably KH171; preferably, the unsaturated quaternary ammonium salt is methacryloyloxyethyl trimethyl ammonium chloride; preferably, the molar ratio of the vinyl silane coupling agent, the unsaturated quaternary ammonium salt, and the acrylamide in step S12 is (0.2-0.4): (0.2-0.3): (0.3-0.6).

[0061] Specifically, step S12 can be performed according to the following process:

[0062] S12, adding vinyl silane coupling agent, unsaturated quaternary ammonium salt, acrylamide, and initiator azobisisobutyronitrile (AIBN) to N,N-dimethylformamide, heating to 80-90°C, and stirring for 6-10h; after the reaction is completed, distilling under reduced pressure, and vacuum drying at 60°C for 6h to obtain intermediate II.

[0063] The usage ratio of vinyl silane coupling agent, unsaturated quaternary ammonium salt, acrylamide and N,N-dimethylformamide is 0.2-0.4mol: 0.2-0.3mol: 0.3-0.6mol: 500mL; the usage of initiator AIBN is 4.0-5.0% of the total weight of the monomer; the purpose of increasing the usage of initiator in the present invention is to appropriately reduce the molecular weight of the target product; the target product with lower molecular weight is conducive to improving its interface enrichment efficiency, and at the same time there is no problem of small molecule residue. The molecular weight of the target product in the present invention is preferably between 10000-20000, and the molecular weight distribution PDI is 2.0-2.5.

[0064] Step S13 in the present invention can be performed as follows:

[0065] S13, adding intermediate product I and intermediate product II to an ethanol aqueous solution, adding acetic acid to adjust the pH value to 4.5-5.5, stirring at room temperature for 2-4 hours, distilling under reduced pressure, and vacuum drying at 60° C. for 8 hours to obtain intermediate product III.

[0066] The dosage ratio of intermediate product I and ethanol aqueous solution is 0.1 mol:500 mL; the dosage ratio of intermediate product I to intermediate product II is 1:1 according to the molar ratio of hydroxyl group to vinyl silane coupling agent; the ethanol content in the ethanol aqueous solution is 95wt%.

[0067] The number of amino functional groups of the polyamino structure in the preferred step S14 of the present invention is ≥ 2; to ensure that the intermediate product III is an amino terminal structure, the number of its amino functional groups must be at least 1 more than the number of acryloxy functional groups, and the amino group can be retained so that the intermediate product III and the target product still have reaction activity, so the polyamino structure can be a diamine structure, a triamine structure or a tetramine structure; specifically, the preferred diamine structure is selected from at least one of isophoronediamine, p-phenylenediamine, o-phenylenediamine, m-phenylenediamine, cyclohexanediamine, ethylenediamine, propylenediamine, tetramethylenediamine, pentamethylenediamine, hexamethylenediamine, and 1,12-diaminododecane; and the preferred diamine structure is isophoronediamine; the preferred triamine structure is selected from at least one of 1,2,3-propylenetriamine, melamine, and 1,3,5-triphenylamine; the preferred tetramine structure is pentaerythritol.

[0068] In the present invention, step S14 can be performed according to the following process:

[0069] S14, adding the polyamino structure to N,N-dimethylformamide A, and adding the intermediate III to N,N-dimethylformamide B, placing in a constant pressure dropping funnel, slowly dropping at room temperature, stirring, after the dropping is completed, continuing to stir for 2-4 hours, filtering, distilling under reduced pressure, and vacuum drying at 40°C for 8 hours to obtain the target product, i.e., uracil-based macromolecule.

[0070] Preferably, in this step, the ratio of the polyamino structure, N,N-dimethylformamide A, and N,N-dimethylformamide B is 0.1 mol: 300 mL: 100 mL; the ratio of the intermediate product III to the polyamino structure is 1:1 in terms of the molar ratio of acryloyloxy to the polyamino structure.

[0071] The uracil-based macromolecule prepared in the present invention first reduces the risk of small molecule residues with a certain molecular weight structure, and then further solves the problem of small molecule residues through molecular structure design and aldehyde-amine condensation reaction.

[0072] In order to take into account the compatibility of the drainage tube for treating glaucoma and the drainage and filtration effect, the present invention preferably has a mass ratio of the amino-containing polymer matrix to the uracil-based macromolecule in the polyamino substance of 100:(3-5).

[0073] In order to take into account the mechanical properties and comfort of the drainage tube for the treatment of glaucoma, the present invention preferably uses a straight-chain fatty aldehyde as the dialdehyde structure, and the number of carbon atoms of the straight-chain fatty aldehyde is 4-8. If the number of carbon atoms is less than 4, the cross-linking reaction is insufficient or the cross-linking density is large, and the material is brittle; if the carbon atoms are greater than 8, the cross-linking density is low and the toughness of the material is poor. In addition, aromatic aldehydes, alicyclic aldehydes, and multi-branched dialdehydes have large steric hindrances, which affect the diffusion efficiency and thus the production efficiency; at the same time, the large steric hindrance structure will also affect the flexibility of the drainage tube, forming a large "foreign body sensation".

[0074] Specifically, the preferred dialdehyde structure of the present invention includes glutaraldehyde; it may also include at least one of succindialdehyde, adipaldehyde, heptanedialdehyde, suberaldehyde, and 2-methylglutaraldehyde.

[0075] In summary, the purpose of the present invention is to develop a drainage tube with anti-cell proliferation, anti-cell adhesion and no small molecule residue in view of the shortcomings of the existing drainage tubes for the treatment of glaucoma. The idea of ​​realization is: design an anti-cell proliferation structure with a certain molecular weight, with uracil as the main raw material, which has excellent anti-cell proliferation effect, and combines the low atomic surface energy of silicon, the antibacterial effect of quaternary ammonium salts, and the water-soluble characteristics of acrylamide to prepare a functional macromolecular monomer with anti-cell proliferation, migration, antibacterial, and water-soluble properties. The theoretical basis for realization is: the ring-opening reaction of carboxyl / amino and epoxy groups, the free radical polymerization reaction of carbon-carbon double bonds, the coupling reaction of hydroxyl and silane, and the Michael addition reaction of acryloxy and amino groups. The uracil-based macromolecule prepared by the above reaction is added to the component mainly composed of gelatin, and the low-temperature solidification characteristics of gelatin are used to cross-link and shape the component mainly composed of aldehyde groups after solidification to obtain a drainage tube for the treatment of glaucoma. The drainage tube solves the problems of cell proliferation and cell adhesion while leaving no small molecule residues. The aldehyde-amine condensation reaction represented by gelatin and glutaraldehyde is highly designable and has practical operational significance.

[0076] Another object of the present invention is to provide a method for preparing a drainage tube for treating glaucoma, the method comprising the following steps:

[0077] S1, dissolve component A according to the formula, remove bubbles, add it into the mold, let it stand for 6-10 hours, and cool it to obtain a primary drainage tube;

[0078] S2, preparing the organic solution of component B according to the formula amount;

[0079] S3, placing the primary drainage tube in the organic solution of component B according to the formula amount, and oscillating the reaction to obtain a cross-linked drainage tube;

[0080] S4, washing the cross-linked drainage tube with alkali, performing oscillation dialysis, and storing it at low temperature to obtain a drainage tube for treating glaucoma.

[0081] Specifically, the preparation method can be carried out according to the following process:

[0082] S1, adding component A to phosphate buffered saline (PBS) solution, heating to 55°C and stirring until completely dissolved, ultrasonically degassing and removing bubbles, maintaining the temperature, injecting component A solution into the mold, standing for 2-4 hours, slowly cooling to 4°C, taking out the molded material, and obtaining a primary drainage tube;

[0083] The dosage ratio of component A to PBS solution is (20-30) g:100 mL;

[0084] S2, adding the aqueous solution of component B to acetonitrile, adding a solid moisture desiccant, sealing and drying for 0.5 h, and filtering to obtain an organic solution of component B;

[0085] The dosage ratio of the aqueous solution of component B, acetonitrile, and solid moisture desiccant is (10-20) mL: (480-490) mL: 100 g;

[0086] The concentration (w / v) of the aqueous solution of component B is 50%;

[0087] S3, placing the primary drainage tube in the organic solution of component B, controlling the temperature at 25°C, and oscillating the reaction for 15-24 hours to obtain a cross-linked drainage tube;

[0088] S4, placing the cross-linked drainage tube in an alkaline solution for 2-4 hours, shaking and dialyzing the tube in a dialysate at 37° C. for 18-24 hours, replacing the dialysate every 4 hours, and storing the tube at 0-8° C. to obtain a final product, i.e., a drainage tube for treating glaucoma;

[0089] The dialysate is physiological saline or PBS solution; preferably physiological saline.

[0090] The preparation method of the drainage tube for treating glaucoma provided by the present invention takes gelatin as the main body, and adds homemade uracil-based macromolecules and aldehyde-based structures to form aldehyde-amine condensation cross-linking; on the one hand, the cross-linking reaction between the amino group and the aldehyde group is a controllable reaction, and the product has strong designability; on the other hand, the uracil-based macromolecules can be effectively migrated by standing still during the preparation process, and the chain entanglement of the macromolecular structure does not have phase separation, thereby forming better performance; the raw materials used in the preparation method are all biological materials or commonly used raw materials, have excellent biological adaptability, and have no small molecule residues, and are safe and non-toxic.

[0091] In order to make the above-mentioned objects, features and advantages of the present invention more obvious and easy to understand, specific embodiments of the present invention are described in detail below with reference to the accompanying drawings.

[0092] Unless otherwise specified, the gelatin in the following examples and comparative examples of the present invention is commercially available animal-derived gelatin; the deacetylation degree of chitosan is ≥95%.

[0093] Example 1

[0094] A method for preparing a uracil-based macromolecule comprises the following steps:

[0095] S11, protected from light, add orotic acid, tetrabutylammonium bromide, glycidyl methacrylate and hydroquinone to tetrahydrofuran, react at 70°C for 20 hours, cool to room temperature, add deionized water A, shake, add ethyl acetate for extraction, take the organic phase, dry it with anhydrous sodium sulfate A, filter, take the filtrate, distill it under reduced pressure, and dry it in vacuo at 40°C for 12 hours to obtain intermediate product I.

[0096] The amount ratio of orotic acid, tetrabutylammonium bromide, glycidyl methacrylate, tetrahydrofuran, deionized water A, ethyl acetate, and anhydrous sodium sulfate A is 0.1 mol: 0.01 mol: 0.1 mol: 200 mL: 300 mL: 600 mL: 5 g.

[0097] The amount of hydroquinone used is 0.1wt% of the mass of glycidyl methacrylate.

[0098] The infrared spectrum of intermediate I is shown in Figure 1 As shown, its infrared data is as follows: 3558cm -1 :-OH exists; 1752cm -1 :-C=O (carboxyl) does not exist; 1735cm -1 :-C=O (ester group) exists; 1676cm -1 :-C=O (amide) exists; 1612cm -1 :-C=C- (pyrimidine) exists; 1555cm -1 : -NH- (amide) exists; 1263cm -1 、893cm -1 、825cm -1 : Epoxy group does not exist; 1604cm -1 、811cm -1 :-C=C-exists.

[0099] S12, add silane coupling agent KH171, methacryloyloxyethyl trimethylammonium chloride, acrylamide, and initiator AIBN to N,N-dimethylformamide, heat to 85°C, and stir for 8.5h; after the reaction, distill under reduced pressure, and vacuum dry at 60°C for 6h to obtain intermediate II ( ).

[0100] The dosage ratio of silane coupling agent KH171, methacryloyloxyethyl trimethyl ammonium chloride, acrylamide, and N,N-dimethylformamide is 0.3 mol: 0.25 mol: 0.45 mol: 500 mL;

[0101] The amount of initiator AIBN used was 4.5% of the total weight of the monomers.

[0102] The infrared spectrum of intermediate II is shown in Figure 2 As shown, its infrared data is as follows: 3324cm -1 :-NH- exists; 1735cm -1 :-C=O (ester group) exists; 1683cm -1 :-C=O (amide) exists; 1615cm -1 :-C=C- does not exist; 1558cm -1: -NH- (amide) exists; 1109 cm -1 、798cm -1 :-Si-O- exists.

[0103] S13, adding intermediate product I and intermediate product II to an ethanol aqueous solution, adding acetic acid to adjust the pH value to 5.0, stirring at room temperature for 2.5 hours, distilling under reduced pressure, and vacuum drying at 60° C. for 8 hours to obtain intermediate product III.

[0104] The usage ratio of intermediate product I and ethanol aqueous solution is 0.1 mol: 0.1 mol: 500 mL;

[0105] The amount ratio of the intermediate product I to the intermediate product II is 1:1 according to the molar ratio of the hydroxyl group to the vinyl silane coupling agent.

[0106] The ethanol content of the ethanol aqueous solution is 95wt%.

[0107] The infrared spectrum of intermediate III is shown in Figure 3 As shown, its infrared data is as follows: 3558cm -1 :-OH does not exist; 3324cm -1 :-NH- exists; 1735cm -1 :-C=O (ester group) exists; 1681cm -1 :-C=O (amide) exists; 1612cm -1 :-C=C- exists; 1557cm -1 : -NH- (amide) exists; 1604cm -1 、811cm -1 :-C=C- exists; 1109 cm -1 、798cm -1 :-Si-O- exists.

[0108] S14, add isophoronediamine to N,N-dimethylformamide A, add the intermediate III to N,N-dimethylformamide B in a constant pressure dropping funnel, slowly add dropwise at room temperature with stirring. After the addition is completed, continue stirring for 3 hours, filter, distill under reduced pressure, and dry in a vacuum at 40°C for 8 hours to obtain the target product, i.e., uracil-based macromolecule.

[0109] The dosage ratio of isophoronediamine, N,N-dimethylformamide A, and N,N-dimethylformamide B is 0.1 mol: 300 mL: 100 mL;

[0110] The ratio of the amount of the intermediate product III to the polyamino structure is 1:1 according to the molar ratio of the acryloyloxy group to the polyamino structure.

[0111] The infrared spectrum of the target product can be found in Figure 4 As shown, its infrared data is as follows: 3331cm -1 :-NH- exists; 1735cm -1 :-C=O (ester group) exists; 1681cm -1 :-C=O (amide) exists; 1612cm -1 :-C=C- (pyrimidine) exists; 1557cm -1 : -NH- (amide) exists; 1604cm -1 、811cm -1 :-C=C- does not exist; 1109 cm -1 、798cm -1 :-Si-O- exists.

[0112] A drainage tube for treating glaucoma, which has a tubular structure;

[0113] The drainage tube for treating glaucoma is prepared by aldehyde amine condensation cross-linking reaction of component A and component B;

[0114] Component A contains polyamino substances;

[0115] Component B is a dialdehyde structure; and

[0116] The polyamino substance is composed of an amino-containing polymer matrix and the self-made uracil-based macromolecule in a mass ratio of 100 g:4.0 g.

[0117] The amino-containing polymer matrix is ​​gelatin;

[0118] The dialdehyde structure is glutaraldehyde.

[0119] The preparation method of the drainage tube for treating glaucoma comprises the following steps:

[0120] S1, adding component A to PBS solution, heating to 55°C and stirring until completely dissolved, ultrasonically degassing and defoaming, injecting component A solution into the mold while maintaining the temperature, standing for 3 hours, slowly cooling to 4°C, taking out the molded material, and obtaining a primary drainage tube;

[0121] The dosage ratio of component A to PBS is 25 g:100 mL;

[0122] S2, adding the aqueous solution of component B to acetonitrile, adding a solid moisture desiccant, sealing and drying for 0.5 h, and filtering to obtain an organic solution of component B;

[0123] The dosage ratio of component B aqueous solution, acetonitrile, and solid moisture desiccant is 20mL:480mL:100g;

[0124] The concentration (w / v) of the aqueous solution of component B is 50%;

[0125] S3, placing the primary drainage tube in the organic solution of component B, controlling the temperature at 25°C, and oscillating the reaction for 20 hours to obtain a cross-linked drainage tube;

[0126] S4, placing the cross-linked drainage tube in an alkaline solution for 4 hours and a dialysate at 37° C. for 22 hours with shaking, during which the dialysate is replaced every 4 hours, and the tube is stored at 4° C. to obtain a final product, i.e., a drainage tube for treating glaucoma;

[0127] The dialysate is normal saline.

[0128] Example 2

[0129] A method for preparing a uracil-based macromolecule comprises the following steps:

[0130] S11, protected from light, add orotic acid, tetrabutylammonium bromide, glycidyl methacrylate and hydroquinone to tetrahydrofuran, react at 65°C for 24 hours, cool to room temperature, add deionized water A, shake, add ethyl acetate for extraction, take the organic phase, dry it with anhydrous sodium sulfate A, filter, take the filtrate, distill it under reduced pressure, and dry it in vacuo at 40°C for 12 hours to obtain intermediate product I.

[0131] Orotic acid, tetrabutylammonium bromide, glycidyl methacrylate, tetrahydrofuran, deionized water A, ethyl acetate, and anhydrous sodium sulfate A were added in the ratio of 0.1 mol: 0.01 mol: 0.1 mol: 200 mL: 300 mL: 600 mL: 5 g;

[0132] The amount of hydroquinone used is 0.1wt% of the mass of glycidyl methacrylate.

[0133] S12, add silane coupling agent KH171, methacryloyloxyethyl trimethylammonium chloride, acrylamide, and initiator AIBN to N,N-dimethylformamide, heat to 90°C, and stir for 6 hours; after the reaction, distill under reduced pressure, and vacuum dry at 60°C for 6 hours to obtain intermediate product II ( ).

[0134] The dosage ratio of silane coupling agent KH171, methacryloyloxyethyl trimethyl ammonium chloride, acrylamide, and N,N-dimethylformamide is 0.3 mol: 0.25 mol: 0.45 mol: 500 mL;

[0135] The amount of initiator AIBN used was 4.0% of the total weight of the monomers.

[0136] S13, adding intermediate product I and intermediate product II to an ethanol aqueous solution, adding acetic acid to adjust the pH value to 4.5, stirring at room temperature for 2 hours, distilling under reduced pressure, and vacuum drying at 60° C. for 8 hours to obtain intermediate product III.

[0137] The usage ratio of intermediate product I and ethanol aqueous solution is 0.1 mol:500 mL;

[0138] The amount ratio of the intermediate product I to the intermediate product II is 1:1 according to the molar ratio of the hydroxyl group to the vinyl silane coupling agent.

[0139] The ethanol aqueous solution has an ethanol content of 95wt%.

[0140] S14, add isophoronediamine to N,N-dimethylformamide A, add the intermediate product II to N,N-dimethylformamide B in a constant pressure dropping funnel, slowly add dropwise at room temperature with stirring. After the addition is completed, continue stirring for 4 hours, filter, distill under reduced pressure, and dry in a vacuum at 40°C for 8 hours to obtain the target product, i.e., uracil-based macromolecule.

[0141] The dosage ratio of isophoronediamine, N,N-dimethylformamide A, and N,N-dimethylformamide B is 0.1 mol: 300 mL: 100 mL;

[0142] The ratio of the amount of the intermediate product III to the polyamino structure is 1:1 according to the molar ratio of the acryloyloxy group to the polyamino structure.

[0143] A drainage tube for treating glaucoma, which has a tubular structure;

[0144] The drainage tube for treating glaucoma is prepared by aldehyde-amine condensation cross-linking reaction of component A and component B;

[0145] Component A contains polyamino substances;

[0146] Component B is a dialdehyde structure; and

[0147] The polyamino substance is composed of an amino-containing polymer matrix and the self-made uracil-based macromolecule in a mass ratio of 100 g:3.0 g.

[0148] The amino-containing polymer matrix is ​​gelatin;

[0149] The dialdehyde structure is glutaraldehyde.

[0150] The preparation method of the drainage tube for treating glaucoma comprises the following steps:

[0151] S1, adding component A to PBS solution, heating to 55°C and stirring until completely dissolved, ultrasonically degassing and defoaming, injecting component A solution into the mold while maintaining the temperature, letting it stand for 4 hours, slowly cooling it to 4°C, taking out the molded material, and obtaining a primary drainage tube;

[0152] The dosage ratio of component A to PBS is 30 g:100 mL;

[0153] S2, adding the aqueous solution of component B to acetonitrile, adding a solid moisture desiccant, sealing and drying for 0.5 h, and filtering to obtain an organic solution of component B;

[0154] The dosage ratio of component B aqueous solution, acetonitrile, and solid moisture desiccant is 10 mL: 490 mL: 100 g;

[0155] The concentration (w / v) of the aqueous solution of component B is 50%;

[0156] S3, placing the primary drainage tube in the organic solution of component B, controlling the temperature at 25°C, and oscillating the reaction for 24 hours to obtain a cross-linked drainage tube;

[0157] S4, placing the cross-linked drainage tube in an alkaline solution for 2 hours and a dialysate at 37° C. for 18 hours with shaking, during which the dialysate is replaced every 4 hours, and the tube is stored at 0° C. to obtain a final product, i.e., a drainage tube for treating glaucoma;

[0158] The dialysate is normal saline.

[0159] Example 3

[0160] A method for preparing a uracil-based macromolecule comprises the following steps:

[0161] S11, protected from light, add orotic acid, tetrabutylammonium bromide, glycidyl methacrylate and hydroquinone to tetrahydrofuran, react at 70°C for 20 hours, cool to room temperature, add deionized water A, shake, add ethyl acetate for extraction, take the organic phase, dry it with anhydrous sodium sulfate A, filter, take the filtrate, distill it under reduced pressure, and dry it in vacuo at 40°C for 12 hours to obtain intermediate product I.

[0162] Orotic acid, tetrabutylammonium bromide, glycidyl methacrylate, tetrahydrofuran, deionized water A, ethyl acetate, and anhydrous sodium sulfate A were added in the ratio of 0.1 mol: 0.01 mol: 0.1 mol: 200 mL: 300 mL: 600 mL: 5 g;

[0163] The amount of hydroquinone used is 0.1wt% of the mass of glycidyl methacrylate.

[0164] S12, add silane coupling agent KH172, methacryloyloxyethyl trimethylammonium chloride, acrylamide, and initiator AIBN to N,N-dimethylformamide, heat to 80°C, and stir for 10 hours; after the reaction, distill under reduced pressure, and vacuum dry at 60°C for 6 hours to obtain intermediate product II ( ).

[0165] The dosage ratio of silane coupling agent KH172, methacryloyloxyethyl trimethyl ammonium chloride, acrylamide, and N,N-dimethylformamide is 0.3 mol: 0.25 mol: 0.45 mol: 500 mL;

[0166] The amount of initiator AIBN used was 5.0% of the total weight of the monomers.

[0167] S13, intermediate product I and intermediate product II were added to an ethanol aqueous solution, acetic acid was added to adjust the pH value to 5.5, and the mixture was stirred at room temperature for 4 h, and then distilled under reduced pressure and dried in vacuum at 60° C. for 8 h to obtain intermediate product II.

[0168] The usage ratio of intermediate product I and ethanol aqueous solution is 0.1 mol:500 mL;

[0169] The amount ratio of the intermediate product I to the intermediate product II is 1:1 according to the molar ratio of the hydroxyl group to the vinyl silane coupling agent.

[0170] The ethanol aqueous solution has an ethanol content of 95wt%.

[0171] S14, add isophoronediamine to N,N-dimethylformamide A, add the intermediate III to N,N-dimethylformamide B in a constant pressure dropping funnel, slowly dropwise add at room temperature with stirring, after the dropwise addition is completed, continue stirring for 2 hours, filter, distill under reduced pressure, and dry in vacuo at 40°C for 8 hours to obtain the target product, i.e., uracil-based macromolecule.

[0172] The dosage ratio of isophoronediamine, N,N-dimethylformamide A, and N,N-dimethylformamide B is 0.1 mol: 300 mL: 100 mL;

[0173] The ratio of the amount of the intermediate product III to the polyamino structure is 1:1 according to the molar ratio of the acryloyloxy group to the polyamino structure.

[0174] A drainage tube for treating glaucoma, which has a tubular structure;

[0175] The drainage tube for treating glaucoma is prepared by aldehyde-amine condensation cross-linking reaction of component A and component B;

[0176] Component A contains polyamino substances;

[0177] Component B is a dialdehyde structure; and

[0178] The polyamino substance is composed of an amino-containing polymer matrix and the self-made uracil-based macromolecule in a mass ratio of 100 g:5.0 g.

[0179] The amino-containing polymer matrix is ​​gelatin;

[0180] The dialdehyde structure is glutaraldehyde.

[0181] The preparation method of the drainage tube for treating glaucoma comprises the following steps:

[0182] S1, adding component A to PBS solution, heating to 55°C and stirring until completely dissolved, ultrasonically degassing and defoaming, injecting component A solution into the mold while maintaining the temperature, standing for 2 hours, slowly cooling to 4°C, taking out the molded material, and obtaining a primary drainage tube;

[0183] The dosage ratio of component A to PBS is 20 g:100 mL;

[0184] S2, adding the aqueous solution of component B to acetonitrile, adding a solid moisture desiccant, sealing and drying for 0.5 h, and filtering to obtain an organic solution of component B;

[0185] The dosage ratio of component B aqueous solution, acetonitrile, and solid moisture desiccant is 20mL:480mL:100g;

[0186] The concentration (w / v) of the aqueous solution of component B is 50%;

[0187] S3, placing the primary drainage tube in the organic solution of component B, controlling the temperature at 25°C, and oscillating the reaction for 15 hours to obtain a cross-linked drainage tube;

[0188] S4, placing the cross-linked drainage tube in an alkaline solution for 4 hours and a dialysate at 37° C. for 24 hours with shaking, during which the dialysate is replaced every 4 hours, and the tube is stored at 8° C. to obtain a final product, i.e., a drainage tube for treating glaucoma;

[0189] The dialysate is normal saline.

[0190] Example 4

[0191] The rest is the same as Example 1, except that in step S14 of the method for preparing uracil-based macromolecules, isophoronediamine is replaced by melamine.

[0192] Example 5

[0193] The rest is the same as Example 1, except that in step S14 of the method for preparing the uracil-based macromolecule, isophoronediamine is replaced by pentaerythritol.

[0194] Example 6

[0195] The rest is the same as Example 1, except that in step S12 of the method for preparing uracil-based macromolecules, the usage ratio of silane coupling agent KH172, methacryloyloxyethyltrimethylammonium chloride, acrylamide, and N,N-dimethylformamide is 0.4 mol: 0.25 mol: 0.35 mol: 500 mL.

[0196] Example 7

[0197] The rest is the same as Example 1, except that in step S12 of the method for preparing uracil-based macromolecules, the usage ratio of silane coupling agent KH172, methacryloyloxyethyltrimethylammonium chloride, acrylamide, and N,N-dimethylformamide is 0.2 mol: 0.25 mol: 0.55 mol: 500 mL.

[0198] Example 8

[0199] The rest is the same as Example 1, except that in step S12 of the method for preparing uracil-based macromolecules, the usage ratio of silane coupling agent KH172, methacryloyloxyethyltrimethylammonium chloride, acrylamide, and N,N-dimethylformamide is 0.3 mol: 0.2 mol: 0.5 mol: 500 mL.

[0200] Example 9

[0201] The rest is the same as Example 1, except that in step S12 of the method for preparing uracil-based macromolecules, the usage ratio of silane coupling agent KH172, methacryloyloxyethyltrimethylammonium chloride, acrylamide, and N,N-dimethylformamide is 0.3 mol: 0.3 mol: 0.4 mol: 500 mL.

[0202] Example 10

[0203] The other steps are the same as those in Example 1, except that in step S11 of the method for preparing uracil-based macromolecules, orotic acid is replaced with 4-aminouracil; the specific steps are as follows:

[0204] S11, protected from light, add 4-aminouracil, triethylamine, glycidyl methacrylate and hydroquinone to tetrahydrofuran, react at 25°C for 6 hours, cool to room temperature, add deionized water A, shake, add ethyl acetate for extraction, take the organic phase, dry it with anhydrous sodium sulfate A, filter, take the filtrate, distill it under reduced pressure, and dry it in vacuo at 40°C for 12 hours to obtain intermediate I.

[0205] 4-aminouracil, triethylamine, glycidyl methacrylate, tetrahydrofuran, deionized water A, ethyl acetate, and anhydrous sodium sulfate A were added in the ratio of 0.1 mol: 0.01 mol: 0.1 mol: 200 mL: 300 mL: 600 mL: 5 g;

[0206] The amount of hydroquinone used is 0.1wt% of the mass of glycidyl methacrylate.

[0207] Embodiment 11

[0208] The rest is the same as Example 1, except that: in component A, the amino-containing polymer matrix is ​​a mixture of gelatin and chitosan, wherein chitosan accounts for 10wt% of the polymer matrix.

[0209] Example 12

[0210] The other parts are the same as those in Example 1, except that component B is succinaldehyde.

[0211] Embodiment 13

[0212] The other parts are the same as those in Example 1, except that component B is suberaldehyde.

[0213] Comparative Examples 1-11 are all compared with Example 1:

[0214] Comparative Example 1

[0215] The rest is the same as Example 1, except that: in component A, the polyamino substance is composed of an amino-containing polymer matrix and uracil-based macromolecules in a mass ratio of 100g:0g; that is, no uracil-based macromolecules are added.

[0216] Comparative Example 2

[0217] The rest is the same as Example 1, except that: in step S12 of the preparation method of uracil-based macromolecules, the silane coupling agent KH171 is replaced by the intermediate product I;

[0218] And, step S13 is as follows:

[0219] S13, protect from light, dissolve the intermediate product II and triethylamine in N,N-dimethylformamide C and place in a reaction container, dissolve acryloyl chloride in N,N-dimethylformamide D and place in a constant pressure dropping funnel, ice bath, stir, after the addition is completed, control the stirring at 0℃ for 12h, after the reaction is completed; filter, distill under reduced pressure, dissolve the concentrate in dichloromethane, add saturated sodium bicarbonate solution to wash 3 times, then wash with deionized water 3 times, separate the liquids, take the organic phase, dry with anhydrous sodium sulfate, filter, distill the filtrate under reduced pressure, and dry in vacuo at 80℃ for 4h to obtain the intermediate product III.

[0220] The dosage ratio of intermediate product II, triethylamine, N,N-dimethylformamide C, acryloyl chloride, N,N-dimethylformamide D, dichloromethane, saturated sodium bicarbonate solution, deionized water, and anhydrous sodium sulfate is: 0.1 mol: 0.12 mol: 100 mL: 0.1 mol: 50 mL: 500 mL: 200 mL: 200 mL: 5 g.

[0221] Comparative Example 3

[0222] The rest is the same as Example 1, except that: in step S12 of the preparation method of the uracil-based macromolecule, the usage ratio of silane coupling agent KH171, methacryloyloxyethyltrimethylammonium chloride, acrylamide, and N,N-dimethylformamide is 0 mol: 0.25 mol: 0.75 mol: 500 mL; that is, the silane coupling agent KH171 is not added.

[0223] Comparative Example 4

[0224] The rest is the same as Example 1, except that: in step S12 of the preparation method of the uracil-based macromolecule, the usage ratio of silane coupling agent KH171, methacryloyloxyethyl trimethylammonium chloride, acrylamide, and N,N-dimethylformamide is 0.3 mol: 0 mol: 0.7 mol: 500 mL; that is, methacryloyloxyethyl trimethylammonium chloride is not added.

[0225] Comparative Example 5

[0226] The rest is the same as Example 1, except that in step S12 of the method for preparing uracil-based macromolecules, the usage ratio of silane coupling agent KH171, methacryloyloxyethyltrimethylammonium chloride, acrylamide, and N,N-dimethylformamide is 0.3 mol: 0.25 mol: 0 mol: 500 mL; that is, acrylamide is not added.

[0227] Comparative Example 6

[0228] The rest is the same as Example 1, except that: Step S12 in the preparation method of uracil-based macromolecule is as follows:

[0229] S12, add silane coupling agent KH171, methacryloyloxyethyl trimethylammonium chloride, acrylamide, initiator AIBN to N,N-dimethylformamide, heat to 80°C, and stir for 12h; after the reaction, distill under reduced pressure, and vacuum dry at 60°C for 6h to obtain intermediate product II ( ).

[0230] The dosage ratio of silane coupling agent KH171, methacryloyloxyethyl trimethyl ammonium chloride, acrylamide, and N,N-dimethylformamide is 0.3 mol: 0.25 mol: 0.45 mol: 500 mL; the dosage of initiator AIBN is 2.5% of the total weight of the monomers.

[0231] Comparative Example 7

[0232] The rest is the same as Example 1, except that: Step S12 in the preparation method of uracil-based macromolecule is as follows:

[0233] S12, add silane coupling agent KH171, methacryloyloxyethyl trimethylammonium chloride, acrylamide, and initiator AIBN to N,N-dimethylformamide, heat to 90°C, and stir for 6 hours; after the reaction, distill under reduced pressure, and vacuum dry at 60°C for 6 hours to obtain intermediate product II ( ).

[0234] The dosage ratio of silane coupling agent KH171, methacryloyloxyethyl trimethyl ammonium chloride, acrylamide, and N,N-dimethylformamide is 0.3 mol: 0.25 mol: 0.45 mol: 500 mL; the dosage of initiator AIBN is 6.0% of the total weight of the monomers.

[0235] Comparative Example 8

[0236] The rest is the same as Example 1, except that: in the drainage tube for treating glaucoma, glutaraldehyde is replaced by glyoxal.

[0237] Comparative Example 9

[0238] The rest is the same as Example 1, except that: in the drainage tube for treating glaucoma, glutaraldehyde is replaced by decanedial.

[0239] Comparative Example 10

[0240] The other parts are the same as those in Example 1, except that glutaraldehyde is replaced by terephthalaldehyde in the drainage tube for treating glaucoma.

[0241] Comparative Example 11

[0242] The other steps are the same as those in Example 1, except that glutaraldehyde is replaced with 2,5-diformylfuran in the drainage tube for treating glaucoma.

[0243] The physical properties of the drainage tubes for treating glaucoma prepared in Examples 1-13 of the present invention and Comparative Examples 1-11 were measured respectively, and the results are shown in Table 1.

[0244]

[0245] Firstly, it can be seen from the data of Examples 1-13 in Table 1 that the drainage tube for treating glaucoma provided by the present invention has excellent properties such as excellent anti-cell proliferation and anti-cell adhesion.

[0246] Second, it can be observed from Example 1 and Comparative Example 1 that the drainage tube for treating glaucoma provided by the present invention introduces a self-made uracil-based macromolecule, which has excellent anti-cell proliferation and anti-cell adhesion properties, and also has excellent drainage efficiency, antibacterial properties, mechanical strength, etc.; it can be observed from Example 1 and Comparative Example 2 that the silane in the self-made uracil-based macromolecule of the present invention has excellent mobility, thereby improving the anti-cell proliferation and adhesion properties; and also has a certain flexibility; it can be observed from Example 1 and Comparative Examples 3-7 that the structural design and molecular weight distribution in the uracil-based macromolecule have a significant impact on the performance of the drainage tube, specifically, the uracil-containing structure has excellent anti-cell proliferation performance, and the silane structure has excellent anti-cell adhesion. The quaternary ammonium salt structure has excellent antibacterial properties, and the macromolecular structure does not dissolve, and has a long-lasting antibacterial effect; and it helps to improve the water solubility and thus improve the drainage efficiency; the acrylamide structure is an excellent hydrophilic substance, which can effectively improve the drainage efficiency of the material; in addition, too large a molecular weight will affect the migration efficiency of the macromolecules; too small a molecular weight and too wide a distribution will deteriorate the strength of the material and there is a risk of small molecule residues; at the same time, the inability to form a complete transition layer will also affect the drainage efficiency; it can be observed from Example 1 and Comparative Examples 8-9 that the molecular structure of the cross-linking agent aldehyde group requires a certain molecular chain length. If the molecular chain is too small or there is a rigid structure, the local cross-linking density will be increased, and the brittleness of the material will increase; if the molecular chain is too long, the material is not elastic enough, which is easy to cause creases.

[0247] In summary, the drainage tube for treating glaucoma provided by the present invention has excellent properties such as anti-cell adhesion, anti-cell proliferation, drainage efficiency, and antibacterial properties, and has great practical significance in ophthalmic treatment.

[0248] The test method is as follows:

[0249] (1) Cytostatic effect test:

[0250] 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 settled, the migration assay was performed by inserting the glaucoma drain 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.

[0251] (2) Cell adhesion test:

[0252] 3T3 mouse embryonic bromide cells were maintained in T-75 Falcon cell culture medium using sterile Dulbecco's modified Falcon medium (DMEM) containing 10% fetal bovine serum (FBS) and 100 units / ml penicillin and 0.1 mg / ml streptomycin. Six samples of each 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.

[0253] (3) Monomer residue test:

[0254] Tested by gas chromatography. Monomer residue expression method: <1ppm is marked as "OK"; >1ppm is marked as "NG".

[0255] (4) Mechanical strength test:

[0256] After folding the drainage device, observe whether there are cracks or creases. The mechanical strength is expressed as follows: no cracks and no creases are recorded as "☆"; no cracks and slight creases that can be restored are recorded as "○"; no cracks and creases are recorded as "◎"; cracks and creases are recorded as "●".

[0257] (5) Drainage efficiency:

[0258] Taking Example 1 as the benchmark, the drainage time of drainage tubes of the same specifications in each example and comparative example is counted. The shorter the time, the higher the efficiency. , t 1 is the drainage time of the drainage tube prepared in Example 1, t n It is the drainage time of the drainage tube prepared in the embodiment or comparative example currently tested.

[0259] (6) Antimicrobial activity value:

[0260] The test was conducted by using a film test in accordance with the method described in WS / T 650-2019. If the antibacterial activity values ​​of the test were all ≥1.0, it could be determined that the sample had an antibacterial effect; if the antibacterial activity values ​​of each test were all ≥2.0, it could be determined that the sample had a strong antibacterial effect; the test strain used was Escherichia coli (8099).

[0261] 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 drainage tube for treating glaucoma, characterized in that: It has a tubular structure; The drainage tube for treating glaucoma is prepared by aldehyde-amine condensation cross-linking reaction of component A and component B; The component A is a substance containing multiple amino groups; The B component is a dialdehyde structure; and The polyamino substance comprises an amino-containing polymer matrix and a uracil-based macromolecule; The uracil-based macromolecule is prepared as follows: S11, performing a ring-opening reaction on an epoxy ring-opening agent containing a uracil structure and an epoxy group containing an acryloxy group to obtain an intermediate product I; S12, subjecting a vinyl silane coupling agent, an unsaturated quaternary ammonium salt, and acrylamide to a free radical polymerization reaction to obtain an intermediate product II; S13, subjecting the intermediate product I to a hydrolysis-coupling reaction with the intermediate product II to obtain an intermediate product III; S14, subjecting the intermediate III and the polyamino structure to Michael addition reaction to obtain a uracil-based macromolecule; The epoxy ring-opening agent containing a uracil structure is an amino-containing uracil or a carboxyl-containing uracil; The unsaturated quaternary ammonium salt is methacryloyloxyethyl trimethylammonium chloride; The amino-containing polymer matrix includes gelatin; In step S12, the initiator selected for the free radical polymerization reaction is azobisisobutyronitrile; the amount of azobisisobutyronitrile used is 4.0-5.0% of the total mass of the monomer; The dialdehyde structure is a straight-chain fatty aldehyde, and the number of carbon atoms of the straight-chain fatty aldehyde is 4-8.

2. The drainage tube for treating glaucoma according to claim 1, characterized in that: The amino-containing uracil is 4-aminouracil.

3. The drainage tube for treating glaucoma according to claim 1, characterized in that: The carboxyl-containing uracil is orotic acid.

4. The drainage tube for treating glaucoma according to claim 1, characterized in that: The epoxy containing acryloxy group is selected from at least one of glycidyl methacrylate and (glycidyloxy)ethyl methacrylate.

5. The drainage tube for treating glaucoma according to claim 1, characterized in that: In step S11, the epoxy ring-opening agent containing a uracil structure and the epoxy containing an acryloxy group are added at a molar ratio of 1:1 between the epoxy ring-opening agent and the epoxy group.

6. The drainage tube for treating glaucoma according to claim 1, characterized in that: In step S12, the molar ratio of the vinyl silane coupling agent, the unsaturated quaternary ammonium salt, and the acrylamide is (0.2-0.4): (0.2-0.3): (0.3-0.6).

7. The drainage tube for treating glaucoma according to claim 1, characterized in that: The number of amino functional groups of the polyamino structure in step S14 is ≥2.

8. The drainage tube for treating glaucoma according to any one of claims 1 to 7, characterized in that: In the polyamino substance, the mass ratio of the amino-containing polymer matrix to the uracil-based macromolecule is 100:(3-5).

9. A method for preparing a drainage tube for treating glaucoma according to any one of claims 1 to 8, characterized in that: The steps include: S1, dissolve component A according to the formula, remove bubbles, add it into the mold, let it stand for 6-10 hours, and cool it to obtain a primary drainage tube; S2, preparing the organic solution of component B according to the formula amount; S3, placing the primary drainage tube in the organic solution of component B according to the formula amount, and oscillating the reaction to obtain a cross-linked drainage tube; S4, washing the cross-linked drainage tube with alkali, performing oscillation dialysis, and storing it at low temperature to obtain a drainage tube for treating glaucoma.

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