Glaucoma drainage tube

Abstract

The invention relates to the field of medical instruments, in particular to a glaucoma drainage tube which comprises a drainage tube body and a drainage channel arranged in the drainage tube body. Wherein the drainage tube body comprises a low critical transition temperature type volume phase change layer. According to the glaucoma drainage tube provided by the invention, the aperture of the drainage channel in the glaucoma drainage tube is adjustable by introducing the low critical transition temperature type volume phase change layer into the drainage tube body, so that the drainage efficiency is adjustable, intraocular pressure is further adjusted by adjusting the drainage efficiency, and the drainage effect is ensured while the drainage effect is ensured. And the application range of the glaucoma drainage tube is expanded.

Description

Technical Field

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

[0002] Glaucoma is the second leading cause of blindness worldwide. It is a type of optic nerve damage caused by pathologically high intraocular pressure. Therefore, controlling intraocular pressure is the main means of treating glaucoma.

[0003] In the prior art, a drainage tube is usually implanted inside the eye to reconstruct the aqueous humor outflow channel, thereby reducing intraocular pressure and achieving the treatment of glaucoma.

[0004] Current research on drainage tubes focuses on how to improve the stability of drainage tube implantation, with less attention paid to the drainage efficiency of drainage tubes. The drainage efficiency of existing drainage tubes is fixed, resulting in poor adaptability of drainage tubes, which affects the drainage effect. Summary of the invention

[0005] In order to solve the problem of fixed drainage efficiency of drainage tubes in the prior art, the present invention provides a glaucoma drainage tube. The glaucoma drainage tube introduces an LCST-type volume phase change layer and a UCST-type volume phase change layer arranged sequentially from the inside to the outside, so that the aperture of the drainage channel of the drainage tube is adjustable, thereby making the drainage efficiency adjustable, thereby solving the problem of fixed drainage efficiency of drainage tubes in the prior art.

[0006] The technical solution adopted by the present invention to solve its technical problem is: A glaucoma drainage tube comprises a drainage tube body and a drainage channel arranged in the drainage tube body; wherein the drainage tube body comprises an LCST type volume phase change layer.

[0007] Optionally, the drainage tube body further includes a UCST type volume phase change layer coated on the outside of the LCST type volume phase change layer.

[0008] Optionally, the LCST type volume phase change layer is prepared by cross-linking copolymerization of N-isopropylacrylamide, hydroxyethyl methacrylate and methyl acrylate.

[0009] Optionally, the LCST type volume phase change layer is prepared by mixing N-isopropylacrylamide, hydroxyethyl methacrylate, methyl acrylate, a crosslinking agent, an initiator and water, and irradiating the mixture under ultraviolet light to obtain the LCST type volume phase change layer.

[0010] Optionally, the molar ratio of the N-isopropylacrylamide, the hydroxyethyl methacrylate, the methyl acrylate, the crosslinking agent, and the initiator is (40-60): (20-30): (20-30): 100:1.

[0011] Optionally, the volume phase change critical temperature of the LCST type volume phase change layer is 36°C.

[0012] Optionally, the UCST type volume phase change layer is prepared by cross-linking copolymerization of N-acryloyl glycinamide and maleic anhydride modified mitomycin.

[0013] Optionally, the preparation method of the UCST type volume phase change layer is as follows: N-acryloyl glycinamide, maleic anhydride modified mitomycin, a crosslinking agent, an initiator and water are mixed, and the mixture is illuminated under ultraviolet light to obtain the UCST type volume phase change layer.

[0014] Optionally, the molar ratio of the N-acryloylglycine amide, the maleic anhydride-modified mitomycin, the cross-linking agent, and the initiator is (80-100): (5-15): 100:1.

[0015] Optionally, the volume phase change critical temperature of the UCST type volume phase change layer is 18°C.

[0016] Optionally, the UCST type volume phase change layer half covers the outer side of the LCST type volume phase change layer.

[0017] Optionally, the UCST type volume phase change layer is a sawtooth structure or a strip structure.

[0018] The beneficial effects of the present invention are: The glaucoma drainage tube provided by the present invention introduces an LCST type volume phase change layer into the drainage tube body, so that the aperture of the drainage channel in the glaucoma drainage tube is adjustable, thereby making the drainage efficiency adjustable. By adjusting the drainage efficiency, the intraocular pressure is further adjusted, and the use range of the glaucoma drainage tube is expanded while ensuring the drainage effect. BRIEF DESCRIPTION OF THE DRAWINGS

[0019] The present invention is further described below in conjunction with the accompanying drawings and embodiments.

[0020] Figure 1 The structure of the glaucoma drainage tube of the present invention is simplified as follows: Figure 1 ; Figure 2 The structure of the glaucoma drainage tube of the present invention is simplified as follows: Figure 2 .

[0021] In the figure: 1- drainage tube body; 11- LCST type volume phase change layer; 12- UCST type volume phase change layer; 2- drainage channel. DETAILED DESCRIPTION

[0022] 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.

[0023] In order to solve the problem that the drainage efficiency of the drainage tube in the prior art is fixed, the present invention provides a glaucoma drainage tube, see Figure 1 As shown, the glaucoma drainage tube includes a drainage tube body 1 and a drainage channel 2 arranged in the drainage tube body 1, and the drainage channel 2 is a through-hole structure for draining the aqueous humor; wherein, the drainage tube body 1 includes an LCST type volume phase change layer 11, and the LCST type volume phase change layer 11 is a tubular structure, and its inner wall encloses the drainage channel 2.

[0024] The LCST volume phase change layer 11 can expand in volume at low temperatures, resulting in an increase in the pore size of the drainage channel 2, thereby improving the drainage efficiency and further achieving regulation of the drainage efficiency of the drainage tube; after the glaucoma drainage tube is implanted, the temperature of the glaucoma drainage tube rises with the temperature of the human body, the volume of the LCST volume phase change layer 11 shrinks, and the pore size of the drainage channel 2 decreases, which helps to reduce the probability of low intraocular pressure; and when the intraocular pressure rises, cold water at 19~35°C can be used to cool the eyes to expand the pore size, increase the drainage efficiency, and achieve regulation of the intraocular pressure.

[0025] The glaucoma drainage tube provided by the present invention introduces an LCST type volume phase change layer 11 into the drainage tube body 1, so that the aperture of the drainage channel 2 in the glaucoma drainage tube is adjustable, thereby making the drainage efficiency adjustable. By adjusting the drainage efficiency, the intraocular pressure is further adjusted, and the use range of the glaucoma drainage tube is expanded while ensuring the drainage effect.

[0026] In order to improve the stability of the glaucoma drainage tube after implantation, the drainage tube body 1 of the present invention preferably further includes a UCST type volume phase change layer 12 coated on the outside of the LCST type volume phase change layer 11 .

[0027] During use of the glaucoma drainage tube, before injection, the glaucoma drainage tube with the UCST type volume phase change layer 12 in a contracted state is first placed in a corresponding injection needle, and after an implantation channel is formed by the injection needle, the glaucoma drainage tube is implanted; after implantation into the eye, the temperature of the glaucoma drainage tube rises with the body temperature, and the UCST type volume phase change layer 12 located on the outside expands, that is, the outer diameter of the glaucoma drainage tube increases, thereby preventing the glaucoma drainage tube from shifting and improving its stability after implantation.

[0028] The present invention introduces the UCST type volume phase change layer 12, which, on the one hand, allows the glaucoma drainage tube to be implanted when the outer diameter is small, which helps to reduce trauma during the implantation process and improve safety; on the other hand, the outer diameter of the glaucoma drainage tube is increased after implantation, thereby preventing it from shifting, improving its stability after implantation, and ensuring the drainage effect.

[0029] In order to take into account both the drainage effect and the biocompatibility, the present invention preferably uses the LCST type volume phase change layer 11 as a poly N-isopropylacrylamide composite material layer. Specifically, the LCST type volume phase change layer 11 is preferably prepared by copolymerizing N-isopropylacrylamide with hydroxyethyl methacrylate and methyl acrylate; wherein hydroxyethyl methacrylate and methyl acrylate are used to adjust the lipophilic and hydrophilic ratio of the system.

[0030] The poly-N-isopropylacrylamide composite material layer provided by the present invention contains HEMA, which helps to further improve its biocompatibility.

[0031] The preferred method for preparing the LCST type volume phase change layer 11 of the present invention is as follows: N-isopropylacrylamide, hydroxyethyl methacrylate, methyl acrylate, a crosslinking agent, an initiator and water are mixed and irradiated under ultraviolet light, preferably for 30 minutes, to obtain an LCST type volume phase change layer 11.

[0032] The preferred crosslinking agent of the present invention is N,N-methylenebisacrylamide, and the initiator is 2-hydroxy-2-methylpropiophenone (1173); further, the preferred molar ratio of N-isopropylacrylamide, hydroxyethyl methacrylate, methyl acrylate, crosslinking agent, and initiator is (40-60): (20-30): (20-30): 100:1.

[0033] In order to ensure the regulating effect of drainage efficiency, the present invention preferably sets the critical temperature of volume phase change of the LCST type volume phase change layer 11 to 36°C.

[0034] In the present invention, the UCST type volume phase change layer 12 is preferably a poly N-acryloyl glycinamide composite material layer, and further preferably the UCST type volume phase change layer 12 is prepared by copolymerization of N-acryloyl glycinamide and maleic anhydride modified mitomycin; wherein mitomycin provides anti-scarring.

[0035] The preparation method of the UCST type volume phase change layer 12 provided by the present invention is as follows: N-acryloyl glycinamide, maleic anhydride-modified mitomycin, a crosslinker, an initiator and water are mixed and illuminated under ultraviolet light to obtain a UCST-type volume phase change layer 12. The preparation method of maleic anhydride-modified mitomycin can refer to the corresponding prior art; for example, the preparation method described in the patent with application number 202310654610.2 can be used.

[0036] The preferred crosslinking agent of the present invention is N,N-methylenebisacrylamide, and the initiator is 2-hydroxy-2-methylpropiophenone (1173); further, the preferred molar ratio of N-acryloylglycinamide, maleic anhydride-modified mitomycin, crosslinking agent, and initiator is (80-100): (5-15): 100: 1.

[0037] In order to take into account both the safety of the implantation process and the stability after implantation, the present invention preferably sets the critical temperature of the volume phase change of the UCST type volume phase change layer 12 to 18°C.

[0038] In order to avoid the expansion of the LCST type volume phase change layer 11 being affected by the constraint of the UCST type volume phase change layer 12, see Figure 2 As shown, the present invention preferably has the UCST type volume phase change layer 12 half-covering the outside of the LCST type volume phase change layer 11, that is, the UCST type volume phase change layer 12 is not a complete annular structure, so as to leave expansion space for the LCST type volume phase change layer 11, thereby ensuring the smooth progress of the intraocular pressure regulation process.

[0039] Furthermore, in the present invention, the UCST volume phase change layer 12 preferably has a sawtooth structure or a strip structure, so as to further reduce the probability of displacement of the glaucoma drainage tube and improve the implantation stability.

[0040] The preferred glaucoma drainage tube of the present invention is prepared by sequentially preparing the LCST type volume phase change layer 11 and the UCST type volume phase change layer 12 by microfluidic technology according to the formula to obtain the glaucoma drainage tube.

[0041] 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.

[0042] Example 1 The present embodiment provides a glaucoma drainage tube, which includes a drainage tube body 1 and a drainage channel 2 arranged in the drainage tube body 1; wherein the drainage tube body 1 includes an LCST type volume phase change layer 11 and a UCST type volume phase change layer 12 coated on the outside of the LCST type volume phase change layer 11; After the glaucoma drainage tube is implanted and stabilized, the thickness of the LCST volume phase change layer 11 is 0.1 mm, the thickness of the UCST volume phase change layer 12 is 0.1 mm, the aperture of the drainage channel 2 is 0.05 mm, and the UCST volume phase change layer 12 is a sawtooth shape.

[0043] The LCST type volume phase change layer 11 is prepared according to the following method: Add 0.05 mol N-isopropylacrylamide, 0.025 mol hydroxyethyl methacrylate, 0.025 mol methyl acrylate, 0.1 mol N,N-methylenebisacrylamide, and 0.001 mol 2-hydroxy-2-methylpropiophenone (1173) into 10 mL of deionized water, stir evenly, and irradiate under ultraviolet light with a wavelength of 355 nm for 30 min.

[0044] The preparation method of the UCST type volume phase change layer 12 is as follows: Add 0.09 mol N-acryloylglycinamide, 0.01 mol maleic anhydride-modified mitomycin, 0.1 mol N,N-methylenebisacrylamide, and 0.001 mol 2-hydroxy-2-methylpropiophenone (1173) into 10 mL of deionized water, stir evenly, and irradiate under ultraviolet light with a wavelength of 355 nm for 30 min.

[0045] Example 2 The difference between this embodiment and embodiment 1 is that the LCST type volume phase change layer 11 is prepared according to the following method: Add 0.04 mol N-isopropylacrylamide, 0.030 mol hydroxyethyl methacrylate, 0.030 mol methyl acrylate, 0.1 mol N,N-methylenebisacrylamide, and 0.001 mol 2-hydroxy-2-methylpropiophenone (1173) into 10 mL of deionized water, stir evenly, and irradiate under ultraviolet light with a wavelength of 355 nm for 30 min.

[0046] The preparation method of the UCST type volume phase change layer 12 is as follows: Add 0.08 mol N-acryloylglycinamide, 0.015 mol maleic anhydride-modified mitomycin, 0.1 mol N,N-methylenebisacrylamide, and 0.001 mol 2-hydroxy-2-methylpropiophenone (1173) into 10 mL of deionized water, stir evenly, and irradiate under ultraviolet light with a wavelength of 355 nm for 30 min.

[0047] Example 3 The difference between this embodiment and embodiment 1 is that the LCST type volume phase change layer 11 is prepared according to the following method: Add 0.06 mol N-isopropylacrylamide, 0.020 mol hydroxyethyl methacrylate, 0.020 mol methyl acrylate, 0.1 mol N,N-methylenebisacrylamide, and 0.001 mol 2-hydroxy-2-methylpropiophenone (1173) into 10 mL of deionized water, stir evenly, and irradiate under ultraviolet light with a wavelength of 355 nm for 30 min.

[0048] The preparation method of the UCST type volume phase change layer 12 is as follows: Add 0.095 mol N-acryloylglycinamide, 0.005 mol maleic anhydride-modified mitomycin, 0.1 mol N,N-methylenebisacrylamide, and 0.001 mol 2-hydroxy-2-methylpropiophenone (1173) into 10 mL of deionized water, stir evenly, and irradiate under ultraviolet light with a wavelength of 355 nm for 30 min.

[0049] Comparative Example 1 The difference between this comparative example and Example 1 is that the LCST type volume phase change layer 11 is prepared according to the following method: Add 0.025 mol hydroxyethyl methacrylate, 0.075 mol methyl acrylate, 0.1 mol N,N-methylenebisacrylamide, and 0.001 mol 2-hydroxy-2-methylpropiophenone (1173) into 10 mL of deionized water, stir evenly, and irradiate under ultraviolet light for 30 min.

[0050] Comparative Example 2 The difference between this comparative example and Example 1 is that the LCST type volume phase change layer 11 is prepared according to the following method: Add 0.75 mol N-isopropylacrylamide, 0.025 mol methyl acrylate, 0.1 mol N,N-methylenebisacrylamide, and 0.001 mol 2-hydroxy-2-methylpropiophenone (1173) into 10 mL of deionized water, stir evenly, and irradiate under ultraviolet light with a wavelength of 355 nm for 30 min.

[0051] Comparative Example 3 The difference between this comparative example and Example 1 is that the LCST type volume phase change layer 11 is prepared according to the following method: Add 0.75 mol N-isopropylacrylamide, 0.025 mol hydroxyethyl methacrylate, 0.1 mol N,N-methylenebisacrylamide, and 0.001 mol 2-hydroxy-2-methylpropiophenone (1173) into 10 mL of deionized water, stir evenly, and irradiate under ultraviolet light with a wavelength of 355 nm for 30 min.

[0052] The performance of the glaucoma drainage tubes prepared in each embodiment and comparative example was tested, and the testing method was as follows: 1) Drainage efficiency was measured at 30°C and 37°C respectively. The measurement method was as follows: 10 ml of deionized water was passed through the drainage tube at a constant flow rate (64 μl / min), and the time required for the deionized water to flow completely was recorded to determine the drainage efficiency; 2) 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 "●".

[0053] 3) 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.

[0054] 4) Outer diameter of drainage tube: simply measure at different temperatures.

[0055] 5) Cell adhesion test: Materials with a diameter of 6 mm were prepared, sterilized by ultraviolet irradiation, and placed in a 96-well cell culture plate. After the cells reached 95% fusion, the cells were digested with 0.25% trypsin, centrifuged and suspended in DMEM / F12 containing 10% fetal bovine serum. Depending on the experiment, the cell seeding density was 1000 or 2000 cells / well. After 24 h of culture, the FDA staining method was used to evaluate the effects of surface modification on cell anti-adhesion and anti-proliferation. Fluorescence images were obtained using a fluorescence microscope (Nikon) using a fluorescein filter (488nm / excitation). ImageJ software was used for cell counting and manual judgment. The less cells adhered, the better the surface anti-scarring effect, reducing the blockage of the drainage tube caused by cell adhesion.

[0056] The test results are shown in Table 1: Table 1 It can be seen from the data in the above table that the glaucoma drainage tubes prepared in each embodiment of the present invention have excellent mechanical properties and excellent anti-cell adhesion properties. At the same time, the drainage efficiency at 30°C is greater than the drainage efficiency at 37°C, which means that the glaucoma drainage tube provided by the present invention can regulate intraocular pressure by lowering the temperature; the outer diameter of the drainage tube at 15°C is smaller than the outer diameter of the drainage tube at 37°C, which means that the glaucoma drainage tube provided by the present invention can improve the stability after implantation by expanding itself after implantation.

[0057] The difference between Comparative Example 1 and Example 1 is that N-isopropylacrylamide is not added during the preparation of the LCST-type volume phase change layer 11, and the drainage efficiency of the prepared glaucoma drainage tube cannot be adjusted by adjusting the temperature.

[0058] The difference between Comparative Example 2 and Example 1 is that hydroxyethyl methacrylate is not added during the preparation of the LCST-type volume phase change layer 11, and the difference between Comparative Example 3 and Example 1 is that methyl acrylate is not added during the preparation of the LCST-type volume phase change layer 11. Although the prepared glaucoma drainage tubes can improve the drainage efficiency by lowering the temperature, the mechanical properties and anti-cell adhesion properties are significantly reduced.

[0059] 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 glaucoma drainage tube, characterized in that: It comprises a drainage tube body (1) and a drainage channel (2) arranged in the drainage tube body (1); wherein the drainage tube body (1) comprises an LCST type volume phase change layer (11).

2. The glaucoma drainage tube according to claim 1, characterized in that: The drainage tube body (1) further comprises a UCST type volume phase change layer (12) coated on the outside of the LCST type volume phase change layer (11).

3. The glaucoma drainage tube according to claim 1, characterized in that: The LCST type volume phase change layer (11) is prepared by cross-linking copolymerization of N-isopropylacrylamide, hydroxyethyl methacrylate and methyl acrylate.

4. The glaucoma drainage tube according to claim 3, characterized in that: The preparation method of the LCST type volume phase change layer (11) is as follows: N-isopropylacrylamide, hydroxyethyl methacrylate, methyl acrylate, a crosslinking agent, an initiator and water are mixed, and the mixture is illuminated under ultraviolet light to obtain the LCST type volume phase change layer (11).

5. The glaucoma drainage tube according to claim 4, characterized in that: The molar ratio of the N-isopropylacrylamide, the hydroxyethyl methacrylate, the methyl acrylate, the crosslinking agent and the initiator is (40-60):(20-30):(20-30):100:

1.

6. The glaucoma drainage tube according to claim 4, characterized in that: The volume phase change critical temperature of the LCST type volume phase change layer (11) is 36°C.

7. The glaucoma drainage tube according to any one of claims 2 to 6, characterized in that: The UCST type volume phase change layer (12) is prepared by cross-linking copolymerization of N-acryloyl glycinamide and maleic anhydride modified mitomycin.

8. The glaucoma drainage tube according to claim 7, characterized in that: The preparation method of the UCST type volume phase change layer (12) is as follows: N-acryloyl glycinamide, maleic anhydride modified mitomycin, a crosslinking agent, an initiator and water are mixed, and the mixture is illuminated under ultraviolet light to obtain the UCST type volume phase change layer (12).

9. The glaucoma drainage tube according to claim 8, characterized in that: The molar ratio of the N-acryloyl glycinamide, the maleic anhydride-modified mitomycin, the crosslinking agent, and the initiator is (80-100): (5-15): 100:

1.

10. The glaucoma drainage tube according to claim 8, characterized in that: The volume phase change critical temperature of the UCST type volume phase change layer (12) is 18°C.

11. The glaucoma drainage tube according to claim 10, characterized in that: The UCST type volume phase change layer (12) is half-covered on the outside of the LCST type volume phase change layer (11).

12. The glaucoma drainage tube according to claim 11, characterized in that: The UCST type volume phase change layer (12) is a sawtooth structure or a strip structure.

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