Drainage disc with shape memory surface pattern, preparation method and drainage valve

Abstract

The invention provides a drainage disc with a shape memory surface pattern, a preparation method and a drainage valve, and relates to the technical field of medical devices for eyes, the drainage disc is made of shape memory polymer, the drainage disc has an initial shape and a temporary shape, the initial shape comprises a groove structure facing the direction of the eyes, and the temporary shape comprises a groove structure facing the direction of the eyes. The temporary shape comprises a flat structure, the temporary shape is configured to be converted into the initial shape from the flat structure under temperature stimulation, and the cell surface morphology of the eye is restrained through the groove structure. The drainage disc is made of the shape memory polymer material, the drainage disc made of the shape memory polymer material recovers to the initial shape under temperature stimulation, the drainage disc with the groove structure is formed, the groove structure generates surface appearance constraint on eye cells, formation of scar tissue is reduced, and therefore the eye cells can be effectively protected. And the operation success rate of implanting the glaucoma drainage device is improved.

Description

Technical Field

[0001] The present invention relates to the technical field of eye medical devices, and in particular to a drainage disk with a shape memory surface pattern, a preparation method and a drainage valve. Background Art

[0002] Glaucoma is the leading cause of irreversible blindness worldwide, and lowering intraocular pressure is its primary treatment. For refractory glaucoma, glaucoma drainage valve implantation is currently the main treatment method at home and abroad, but the success rate of this implantation is low, mainly because scars are easily formed around the drainage valve, and the formation of this scar involves a complex and dynamic cascade process, including four stages: coagulation, inflammation, proliferation, and remodeling of damaged tissue. Specifically, scar formation around the drainage valve is caused by inflammatory cell activation and activation, proliferation, and extracellular matrix secretion of Tenon's capsule fibroblasts, which increases the outflow resistance of aqueous humor in the filtration area and causes increased intraocular pressure. As the first stage of foreign body reaction, the inflammatory stage plays a leading role in wound healing and tissue regeneration, and its severity and duration are related to the degree of scarring. If the early M1 macrophages fail to transform into the M2 phenotype at a specific time point (3-4d) and continue to secrete proinflammatory cytokines, chronic inflammation and scar formation will occur. The proliferation phase is another key stage of wound healing, during which fibroblasts proliferate, activate, and produce ECM. Myofibroblasts are a type of smooth muscle-like contractile cell derived from fibroblasts and are the key triggers of implant-induced fibrotic responses, leading to positive feedback and dense scar formation. Therefore, in order to reduce postoperative scar formation, it is crucial to explore new methods for regulating cell behavior. Summary of the invention

[0003] The problem solved by the present invention is how to solve the problem of scarring of the filtration area caused by implantation of a glaucoma drainage valve.

[0004] To solve the above problems, the present invention provides a drainage disk with a shape memory surface pattern for use in the eye, wherein the drainage disk is made of a shape memory polymer, and has an initial shape and a temporary shape, wherein the initial shape includes a groove structure facing the eye, and the temporary shape includes a flat structure, and the temporary shape is configured to be transformed from the flat structure to the initial shape under temperature stimulation, and the groove structure is used to achieve constraint on the cell surface morphology of the eye.

[0005] Furthermore, the temperature is 40-42°C.

[0006] The advantage of the drainage disc with a shape memory surface pattern described in the present invention over the prior art is that the present invention uses a shape memory polymer material to make a drainage disc, and can implant a drainage disc with a temporary shape and a flat structure into the eye. When a temperature stimulus is given at an appropriate time, the drainage disc made of the shape memory polymer material is restored to its initial shape under the temperature stimulus, forming a drainage disc with a groove structure. The groove structure exerts surface morphology constraints on eye cells, and achieves superior use of the body's own immune repair ability to regulate the inflammatory response of biomaterials. Moreover, under temperature stimulation, the drainage disc realizes the transformation between the initial shape and the temporary shape, and the operation is simple. The deformable surface pattern can effectively regulate the phenotypic conversion of inflammatory cells in the eye, inhibit the proliferation and activation of fibroblasts, induce the distribution of deposited collagen, and control the directional arrangement and growth morphology of cells, which can not only regulate the phenotypic conversion of macrophages but also promote wound healing, reduce the formation of scar tissue, and improve the surgical success rate of glaucoma drainage device implantation.

[0007] The present invention also provides a method for preparing the drainage disk having a shape memory surface pattern as described above, comprising the following steps:

[0008] Step S1: designing a pattern of a groove structure, and photolithography the pattern on a template to obtain a groove structure template;

[0009] Step S2: fully mix the shape memory polymer, hydrogel and curing agent, remove bubbles, pour them onto the groove structure template, heat and cure them, and separate them to obtain the groove structure drainage disk in its initial shape.

[0010] Furthermore, in step S1, the grooves in the groove structure are arranged in parallel and uniformly, wherein the width of the grooves is 5 μm-20 μm; the spacing between the grooves is 10 μm-20 μm; and the depth of the grooves is 2 μm-5 μm.

[0011] Furthermore, in step S2, the shape memory polymer includes at least one of polylactic acid, polycaprolactone or polyurethane.

[0012] Furthermore, in step S2, the hydrogel includes a shape memory hydrogel made of at least one of gelatin, acrylamide, hyaluronic acid, polyvinyl alcohol, chitosan, and agar.

[0013] Further, in step S2, the curing agent includes a thermal initiator and a photoinitiator; the thermal initiator includes a persulfide; the photoinitiator includes 2-hydroxy-2-methyl-1-phenyl-1-propanone, 2-hydroxy-4′-(2-hydroxyethoxy)-2-methylpropiophenone or phenyl-2,4,6-trimethylbenzoyl lithium phosphonate.

[0014] The advantage of the method for preparing a drainage disc with a shape memory surface pattern described in the present invention over the prior art is that the preparation method of the present invention requires fewer types of raw materials, has simple steps, and is easy to operate. The drainage disc prepared by the preparation method of the present invention can effectively regulate the phenotypic conversion of inflammatory cells in the eye, induce the distribution of fibroblasts and deposited collagen, control the directional arrangement and growth morphology of cells, regulate the phenotypic conversion of macrophages, promote wound healing, reduce the formation of scar tissue, and improve the surgical success rate of glaucoma drainage device implantation.

[0015] The present invention also provides a drainage valve with a shape memory surface pattern, comprising a drainage tube and a connection structure connected in sequence, and a drainage disk made based on any of the above-mentioned methods for preparing a drainage disk with a shape memory surface pattern.

[0016] Furthermore, the connection structure includes a base portion and a shielding portion, wherein the shielding portion is arranged at one end of the base portion facing the eye direction and is arranged close to the tube opening of the drainage tube.

[0017] Furthermore, a through hole is provided on the shielding portion, and one end of the through hole is arranged toward the eye.

[0018] The advantages of the drainage valve with a shape memory surface pattern described in the present invention over the prior art are the same as the advantages of the preparation method of the drainage disc with a shape memory surface pattern described in the present invention over the prior art, which will not be repeated here. In addition, the drainage valve with a shape memory surface pattern for glaucoma is easy to disinfect, package and transport, and is a low-cost, convenient and feasible glaucoma drainage device. BRIEF DESCRIPTION OF THE DRAWINGS

[0019] Figure 1 Schematic diagram of the preparation process of the drainage disk with a shape memory surface pattern in an embodiment of the present invention;

[0020] Figure 2 is a flow chart of a method for preparing a drainage disk having a shape memory surface pattern in an embodiment of the present invention;

[0021] Figure 3 This is a schematic diagram of the working process of the drainage valve with a shape memory surface pattern in Example 1 of the present invention;

[0022] Figure 4 Schematic diagram of the connection structure of a drainage valve with a shape memory surface pattern in an embodiment of the present invention.

[0023] Description of reference numerals:

[0024] 1-drainage tube; 21-base; 22-shielding portion; 23-through hole; 24-connecting rod. DETAILED DESCRIPTION

[0025] 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.

[0026] Combination Figure 3 As shown, an embodiment of the present invention provides a drainage disk with a shape memory surface pattern, which is used for the eye. The drainage disk is made of a shape memory polymer. The drainage disk has an initial shape and a temporary shape. The initial shape includes a groove structure facing the eye, and the temporary shape includes a flat structure. The temporary shape is configured to change from the flat structure to the initial shape under temperature stimulation, and the groove structure is used to achieve constraint on the cell surface morphology of the eye.

[0027] The drainage disk in this embodiment is provided with a groove structure toward the eye. In order to realize the regulation function of the surface morphology constraint on the cells, the groove structure is designed to be regularly arranged stripe-shaped grooves according to the characteristics of macrophages and fibroblasts, such as Figure 1 and Figure 3 As shown, the striped groove structure helps to transform macrophages from M1 phenotype to M2 phenotype at the appropriate time point, reducing postoperative inflammation; at the same time, the groove structure can control the directional arrangement and growth morphology of cells, inhibit the excessive proliferation and activation of Tenon capsule fibroblasts, induce uniform collagen deposition, and thus achieve the role of surface morphology constraint. By simulating the ever-changing physiological conditions during the healing process, the wound healing response is actively adjusted, wound healing is promoted, foreign body reactions and scar formation are reduced, and the incidence of scarring in the filtration area after glaucoma drainage valve surgery is reduced. Compared with static biomaterials that cannot simulate ever-changing physiological conditions, the drainage disc in the embodiment of the present invention uses the surface morphology of biomaterials to achieve dynamic regulation, which is closer to the dynamic characteristics of wound healing and tissue regeneration, and is more conducive to reducing scar formation.

[0028] The drainage disc with a shape memory surface pattern described in the embodiment of the present invention is made of a shape memory polymer material. The drainage disc with a temporary shape and a flat structure can be implanted into the eye. Temperature stimulation is given at an appropriate time, so that the drainage disc made of the shape memory polymer material is transformed into the initial shape under the temperature stimulation, forming a drainage disc with a groove structure. The groove structure exerts surface morphology constraints on the eye cells, and achieves superior use of the body's own immune repair ability to regulate the inflammatory response of the biomaterial. Moreover, under temperature stimulation, the drainage disc realizes the transformation between the initial shape and the temporary shape, and the operation is simple. The deformable surface pattern can control the directional arrangement and growth morphology of the cells, effectively regulate the phenotypic conversion of the inflammatory cells in the eye, inhibit the proliferation and activation of fibroblasts and the deposition of collagen, and can both regulate the phenotypic conversion of macrophages and promote wound healing, reduce the formation of scar tissue, and improve the surgical success rate of glaucoma drainage device implantation.

[0029] In some specific embodiments, the temperature is 40-42° C. Thus, the induction factor close to the human body temperature is used, which will not cause damage to the eyes, and the temperature is suitable for realization and precise control, reducing the difficulty of application.

[0030] Combination Figure 1 and Figure 2 The embodiment of the present invention further provides a method for preparing the drainage disk having a shape memory surface pattern as described above, comprising the following steps:

[0031] Step S1: designing a pattern of a groove structure, and photolithography the pattern on a template to obtain a groove structure template;

[0032] Step S2: fully mix the shape memory polymer, hydrogel and curing agent, remove bubbles, pour them onto the groove structure template, heat and cure them, and separate them to obtain a groove structure drainage disk in its original shape.

[0033] Specifically, the template in step S1 can be made of polydimethylsiloxane, which is conducive to molding. Figure 1 In the above figure, a is a template.

[0034] Specifically, in step S2, the shape memory polymer and hydrogel are mixed and dissolved uniformly, and then a curing agent is added. Through the designed groove structure pattern, a drainage disk is prepared, and the drainage disk is in an initial shape. If it is needed, the surface of the groove structure is processed to form a flat structure. After it is in a temporary shape, it is placed in the corresponding position of the eye and waits for later regulation. Figure 1 b in the figure shows the shape memory polymer mixture poured onto the groove structure template, and c shows the groove structure drainage plate in the initial shape after separation.

[0035] The method for preparing a drainage disk with a shape memory surface pattern described in an embodiment of the present invention requires few types of raw materials, has simple steps, and is easy to operate. The drainage disk prepared by the preparation method of the present invention can control the directional arrangement and growth morphology of cells, effectively regulate the phenotypic conversion of inflammatory cells in the eye, inhibit the proliferation and activation of fibroblasts and the deposition of collagen, regulate the phenotypic conversion of macrophages, promote wound healing, reduce the formation of scar tissue, and improve the success rate of glaucoma drainage device implantation.

[0036] In some specific embodiments, in step S1, the grooves in the groove structure are arranged in parallel and uniformly, wherein the width of the grooves is 5 μm-20 μm; the spacing between the grooves is 10 μm-20 μm; and the depth of the grooves is 2 μm-5 μm.

[0037] Specifically, in order to better realize the regulatory function of surface morphology constraints on cells, the optimal groove width, spacing and depth are designed according to the characteristics of macrophages and fibroblasts to control the arrangement direction and growth morphology of cells, induce uniform collagen deposition, inhibit the excessive proliferation of Tenon capsule fibroblasts and extracellular matrix secretion, realize dynamic regulation of the surface morphology of biomaterials, reduce foreign body reactions and scar formation, and reduce the incidence of scarring in the filtration area after glaucoma drainage valve surgery.

[0038] In some specific embodiments, in step S2, the shape memory polymer includes at least one of polylactic acid, polycaprolactone or polyurethane.

[0039] Therefore, experimental materials are easily available and widely selected, which is conducive to the industrial production of drainage trays.

[0040] In some specific embodiments, in step S2, the hydrogel includes a shape memory hydrogel made of at least one of gelatin, acrylamide, hyaluronic acid, polyvinyl alcohol, chitosan, and agar.

[0041] Thus, a wide range of hydrogels can be selected, which is beneficial for the preparation of drainage trays.

[0042] In some specific embodiments, in step S2, the curing agent includes a thermal initiator and a photoinitiator; the thermal initiator includes a persulfide; the photoinitiator includes 2-hydroxy-2-methyl-1-phenyl-1-propanone, 2-hydroxy-4′-(2-hydroxyethoxy)-2-methylpropiophenone or phenyl-2,4,6-trimethylbenzoyl lithium phosphonate.

[0043] Specifically, the persulfide thermal initiator includes common thermal initiators such as ammonium persulfate and potassium persulfate. The curing agent has a wide range of choices and is of various types, which is conducive to the preparation and performance control of the drainage disk.

[0044] Based on the above embodiment of the drain plate, the present invention also provides another method for preparing a drain plate with a shape memory surface pattern:

[0045] Specifically, gelatin and polyvinyl alcohol are dissolved in deionized water, and the mixture is heated to 80°C to completely dissolve gelatin and polyvinyl alcohol, and at the same time, a first network of gelatin is formed; a photoinitiator cystine bisacrylamide is added to the solution. The prepared gelatin and polyvinyl alcohol solution is poured onto a silicon wafer template with a surface microstructure, and then the solution is placed in a refrigerator at -18°C to freeze, and cystine bisacrylamide and polyvinyl alcohol are cross-linked by ultraviolet light while maintaining the frozen state to form a second network; at the same time, a hydrogel with a surface microstructure is formed; the frozen hydrogel is placed at room temperature and thawed, and the physical cross-linking of polyvinyl alcohol is promoted by multiple freeze-thaw cycles to increase the mechanical properties of the hydrogel. At the same time, due to the cross-linking of cystine bisacrylamide and polyvinyl alcohol, the morphology of the surface microstructure can be maintained; the patterned gelatin / polyvinyl alcohol hydrogel is peeled off from the silicon wafer template to complete the manufacturing process, and a drainage disk with a shape memory surface pattern is obtained. The mass ratio of gelatin to polyvinyl alcohol described in this embodiment is 1: (9.9-11.1). The temporary shape can be obtained by flattening the surface of the drainage disk at 40°C, and the temporary shape can also return to the initial shape by itself under the temperature stimulation of 40-42°C. Although the temperature conditions of the preparation are different, they are all relatively easy to achieve preparation conditions, and the steps are simple and easy to operate, which is conducive to the large-scale production of the drainage disk.

[0046] like Figure 3 As shown, the present invention also provides a drainage valve with a shape memory surface pattern, comprising a drainage tube 1 connected in sequence, a connection structure and a drainage disk made based on the preparation method of the drainage disk with a shape memory surface pattern described in any one of the above items.

[0047] The advantages of the drainage valve with a shape memory surface pattern described in the embodiment of the present invention over the prior art are the same as the advantages of the preparation method of the drainage disc with a shape memory surface pattern described in the embodiment of the present invention over the prior art, which will not be repeated here. In addition, the drainage valve with a shape memory surface pattern for glaucoma is easy to disinfect, package and transport, and is a low-cost, convenient and feasible glaucoma drainage device.

[0048] In some specific embodiments, the connection structure includes a base portion 21 and a shielding portion 22 , wherein the shielding portion 22 is disposed at one end of the base portion 21 facing the eye and is disposed close to the tube opening of the drainage tube 1 .

[0049] Specifically, Figure 4As shown, the base 21 is connected to the drainage tube 1. The base 21 is a rectangular parallelepiped, and a connecting rod is provided at one end facing the drainage plate for connecting the drainage plate. Preferably, there are four connecting rods 24, which are respectively arranged at the four inner corners of the rectangular parallelepiped base 21 to achieve a fixed connection with the end of the drainage plate. This is more conducive to achieving a stable connection between the drainage plate and the base 21 of the connection structure.

[0050] In some specific embodiments, a through hole 23 is provided on the shielding portion 22, and one end of the through hole 23 is arranged toward the eye.

[0051] Specifically, sutures can be passed through the through hole 23 to achieve connection with the sclera at the equator of the eyeball, which effectively solves the problem that materials with low modulus and toughness cannot be effectively fixed, and is conducive to improving the success rate of the operation.

[0052] Example 1

[0053] A drainage valve with a shape memory surface pattern comprises a drainage tube 1, a connection structure and a drainage disc based on the above-mentioned which are connected in sequence, specifically:

[0054] Step 1: Preparation of drainage tube: construct a three-dimensional structural model of the drainage tube, use medical-grade silicone raw materials, and print the drainage tube according to the three-dimensional structure by a 3D printing method to prepare a hollow tubular structure with a length of 6 mm, an inner diameter of 0.3 mm, and an outer diameter of 0.6 mm;

[0055] Step 2: Preparation of connection structure: Construct a three-dimensional structural model of the connection structure, use medical grade silicone raw materials, and print the connection structure according to the three-dimensional structure by 3D printing method. The connection structure is divided into three parts: the first part is the base 21, which is a rectangular structure with a specific length of 8mm, a width of 3mm, and a thickness of 2mm. Its function is to serve as a base, one side of which is connected to the drainage tube and the other side is connected to the drainage disk. Both ends of the base 21 have through holes 23 with a diameter of 0.3mm, and the suture can pass through the through holes 23 to connect the drainage valve The second part is a connecting rod 24, which is a cylindrical structure with a length of 1 mm and a diameter of 0.3 mm. The connecting rod 24 is connected to the four corners of the base 21 respectively, and its function is to connect the shape memory drainage disk and the base 21; the third part is a shielding part 22, which is a rectangular parallelepiped structure with a length of 8 mm, a width of 3 mm, and a thickness of 0.5 mm. Its function is to cover the opening end of the drainage disk of the drainage tube 1, play a role in fixing and shielding the drainage tube 1, prevent the growth of scar tissue, and reduce the probability of blockage of the tube opening;

[0056] Step 3: Drainage tray preparation

[0057] Step S1: designing a pattern of a groove structure, and photolithography the pattern on a template to obtain a groove structure template;

[0058] Step S2: fully mixing the shape memory polymer, the hydrogel and the curing agent, removing bubbles, pouring them onto the groove structure template, and separating them after heating and curing to obtain the groove structure drainage plate in the initial shape; the drainage plate has a width of 8 mm, a length of 10 mm and a thickness of 2 mm;

[0059] The drainage disc with the pattern is subjected to a surface shaping treatment to obtain a temporary structure with a smooth surface. Finally, a drainage valve with a shape memory surface pattern is obtained by connection.

[0060] Although the present invention is disclosed as above, the protection scope of the present invention is not limited thereto. Those skilled in the art may make various changes and modifications without departing from the spirit and scope of the present invention, and these changes and modifications will fall within the protection scope of the present invention.

Claims

1. A drainage disc with a shape memory surface pattern, for use in the eye, characterized in that: The drainage disk is made of a shape memory polymer and has an initial shape and a temporary shape. The initial shape includes a groove structure facing the eye, and the temporary shape includes a flat structure. The temporary shape is configured to be transformed from the flat structure to the initial shape under temperature stimulation, and the groove structure is used to achieve constraint on the cell surface morphology of the eye.

2. The drain plate with a shape memory surface pattern according to claim 1, characterized in that: The temperature is 40-42°C.

3. A method for preparing a drainage plate having a shape memory surface pattern as claimed in claim 1 or 2, characterized in that: The steps include: Step S1: designing a pattern of a groove structure, and photolithography the pattern on a template to obtain a groove structure template; Step S2: fully mix the shape memory polymer, the hydrogel and the curing agent, remove the bubbles, pour them onto the groove structure template, heat and cure them, and separate them to obtain a drainage disk in its initial shape.

4. The method for preparing a drain plate having a shape memory surface pattern according to claim 3, characterized in that: In step S1, the grooves in the groove structure are arranged in parallel and uniformly, wherein the width of the grooves is 5 μm-20 μm; the spacing between the grooves is 10 μm-20 μm; and the depth of the grooves is 2 μm-5 μm.

5. The method for preparing a drain plate having a shape memory surface pattern according to claim 3, characterized in that: In step S2, the shape memory polymer includes at least one of polylactic acid, polycaprolactone or polyurethane.

6. The method for preparing a drain plate having a shape memory surface pattern according to claim 3, characterized in that: In step S2, the hydrogel includes a shape memory hydrogel made of at least one of gelatin, acrylamide, hyaluronic acid, polyvinyl alcohol, chitosan, and agar.

7. The method for preparing a drain plate having a shape memory surface pattern according to claim 3, characterized in that: In step S2, the curing agent includes a thermal initiator and a photoinitiator; the thermal initiator includes a persulfide; the photoinitiator includes 2-hydroxy-2-methyl-1-phenyl-1-propanone, 2-hydroxy-4′-(2-hydroxyethoxy)-2-methylpropiophenone or phenyl-2,4,6-trimethylbenzoyl lithium phosphonate.

8. A drainage valve having a shape memory surface pattern, characterized in that: The invention comprises a drainage tube and a connection structure connected in sequence and a drainage plate made by the preparation method of the drainage plate with a shape memory surface pattern according to any one of claims 3 to 7.

9. The drainage valve with a shape memory surface pattern according to claim 8, characterized in that: The connecting structure comprises a base portion and a shielding portion. The shielding portion is arranged at one end of the base portion facing the eye direction and is arranged close to the tube opening of the drainage tube.

10. The drainage valve with a shape memory surface pattern according to claim 9, characterized in that: The shielding portion is provided with a through hole, and one end of the through hole is arranged toward the eye.

Images