Nerve repair catheter and preparation method thereof

Abstract

The present invention provides a nerve repair catheter and a preparation method thereof, and relates to the technical field of medical biomaterials. The nerve repair catheter is mainly prepared from biodegradable materials by a casting method, wherein: the outer surface of the nerve repair catheter has a grooved structure, and the grooved structure can enable a large amount of muscle and vascular tissue to grow in large quantities along the grooves on the outer surface of the catheter, which is beneficial to the rapid growth and repair of tissues; at the same time, the inner surface of the nerve repair catheter also has a growth guide structure, such as longitudinal parallel grooves, which can be used to guide nerve growth, which is beneficial to the directional guidance of the proximal newly generated nerve bundles to the corresponding distal target area, thereby improving the accuracy of nerve repair. Therefore, the nerve repair catheter of the present application has a better nerve defect repair effect as a nerve defect repair body.

Description

Technical Field

[0001] The invention relates to the technical field of medical biomaterials, and in particular to a nerve repair catheter and a preparation method thereof. Background Art

[0002] The replacement and repair of peripheral nerve defects after injury has always been a global problem. Currently, the main clinical method for repairing peripheral nerve defects is autologous nerve transplantation, but the source of autologous nerves is limited, and it will cause secondary damage to the human body. The operation is difficult and it is difficult for patients to fully recover. Using artificial synthetic grafts as scaffolds to repair peripheral nerve defects has been a hot topic in the field of peripheral nerve research in recent years, hoping to replace autologous nerves to repair nerve defects.

[0003] An ideal nerve repair catheter should have the following characteristics: 1. The nerve repair catheter is biodegradable, and the degradation rate can be controlled; 2. The nerve repair catheter has certain mechanical properties and can provide growth space and mechanical strength for the nerves; 3. It has good biocompatibility and does not affect tissue activity and function; 4. It has a certain porosity, and substances can be exchanged inside and outside the nerve repair catheter.

[0004] In view of this, based on the characteristics of an ideal nerve repair catheter, the present invention uses bioabsorbable materials to prepare a nerve repair catheter. Summary of the invention

[0005] The first object of the present invention is to provide a nerve repair catheter, which has a better nerve defect repairing effect as a nerve defect repair body.

[0006] The second object of the present invention is to provide a method for preparing a nerve repair catheter.

[0007] The present invention provides a nerve repair catheter, which is mainly prepared by a biodegradable material through a casting method, wherein:

[0008] The outer surface of the nerve repair catheter has a grooved structure;

[0009] And / or, the inner surface of the nerve repair conduit has a growth guiding structure.

[0010] Furthermore, the nerve repair catheter includes a single-layer structure nerve repair catheter or a multi-layer structure nerve repair catheter;

[0011] Preferably, the multi-layer structure nerve repair catheter includes a double-layer structure nerve repair catheter or a triple-layer structure nerve repair catheter.

[0012] Furthermore, the inner diameter of the single-layer structure nerve repair catheter is 1 to 15 mm, the thickness is 0.1 to 1.5 mm, and the pore size is 0 to 30 μm;

[0013] Preferably, the inner diameter of the inner layer of the double-layer structure nerve repair catheter is 0.8-15 mm, the thickness of the inner layer is 0.08-1.5 mm, and the pore size of the inner layer is 30-200 μm; the inner diameter of the outer layer is 1.1-16.5 mm, the thickness of the outer layer is 0.1-1.5 mm, and the pore size of the outer layer is 0-30 μm;

[0014] Preferably, the inner diameter of the inner layer of the three-layer nerve repair catheter is 0.8-14.5 mm, the thickness of the inner layer is 0.06-1.5 mm, and the pore size of the inner layer is 30-200 μm; the inner diameter of the middle layer is 1.0-16 mm, the thickness of the middle layer is 0.08-1.5 mm, and the pore size of the middle layer is 50-300 μm; the inner diameter of the outer layer is 1.1-16 mm, the thickness of the outer layer is 0.06-1.5 mm, and the pore size of the outer layer is 0-30 μm.

[0015] Furthermore, the inner layer of the multi-layered nerve repair catheter is a plurality of bundles of small tubes arranged in parallel.

[0016] Preferably, the inner diameter of the multiple bundles of small tubes is 0.8-14.5 mm, the thickness is 0.01-0.8 mm, and the pore size is 30-200 um.

[0017] Furthermore, the degradable biomaterial includes at least one of polylactic acid, polycaprolactone, polyhydroxyalkanoate, polybutylene succinate, polybutylene terephthalate-adipate-butylene ester, polyvinyl alcohol, and polycarbonate.

[0018] Furthermore, positioning structures or fixing structures are provided at both ends of the nerve repair catheter.

[0019] Furthermore, the positioning structure includes at least one of a positioning hole, a positioning groove or a positioning protrusion;

[0020] Preferably, the fixing structure comprises at least one of a flare, a spike or a barb.

[0021] The present invention provides a method for preparing the above-mentioned nerve repair catheter, the preparation method comprising the following steps:

[0022] (a) dissolving a degradable biomaterial in a non-alcoholic polar solvent to obtain a solution A; then adding a porogen and stirring until the porogen is evenly distributed to obtain a pipe-making solution;

[0023] (b) immersing a cylindrical tube-making jig into the tube-making solution, so that a layer of the tube-making solution adheres to the surface of the tube-making jig, and then taking it out and letting it stand; then demolding and removing the solvent, and drying to obtain a nerve repair catheter;

[0024] Optionally, step (b) is repeated once to obtain a double-layer structure nerve repair catheter; or step (b) is repeated twice to obtain a three-layer structure nerve repair catheter.

[0025] Furthermore, the non-alcohol polar solvent includes at least one of tetrahydrofuran, ethylene dichloride, dimethyl ether or N,N-dimethylformamide.

[0026] Furthermore, the porogen includes at least one of sodium chloride, sucrose, gelatin balls, monosodium glutamate, modified cellulose, urea, polyethylene glycol, and polyvinyl pyrrolidone.

[0027] Compared with the prior art, the present invention has the following beneficial effects:

[0028] The nerve repair catheter provided by the present application is mainly prepared by a casting method using a biodegradable material, wherein: the outer surface of the nerve repair catheter has a grooved structure, and the grooved structure can allow a large amount of muscle and vascular tissue to grow in large quantities along the outer surface grooves of the catheter, which is conducive to rapid tissue growth and repair; at the same time, the inner surface of the nerve repair catheter also has a growth guide structure, such as longitudinal parallel grooves, which can be used to guide nerve growth, which is conducive to directional guidance of the proximal newborn nerve bundle to the corresponding distal target area, thereby improving the accuracy of nerve repair. Therefore, the nerve repair catheter of the present application has a better nerve defect repair effect as a nerve defect repair body.

[0029] The preparation method of the nerve repair catheter provided by the present invention comprises the following steps: firstly dissolving a degradable biomaterial in a non-alcoholic polar solvent, and then adding a porogen to prepare a tube-making solution; then immersing a cylindrical tube-making jig in the tube-making solution, so that a layer of the tube-making solution adheres to the surface of the tube-making jig, and then taking it out and letting it stand; then demolding and removing the solvent, and drying to prepare the nerve repair catheter; the preparation method adopts a tape casting method to prepare the nerve repair catheter, and has the advantages of simple processing technology and easy operation. BRIEF DESCRIPTION OF THE DRAWINGS

[0030] In order to more clearly illustrate the specific implementation methods of the present invention or the technical solutions in the prior art, the drawings required for use in the specific implementation methods or the description of the prior art will be briefly introduced below. Obviously, the drawings described below are some implementation methods of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying creative work.

[0031] Figure 1 The inner layer structure diagram of the nerve repair conduit provided by the present invention when sugar is a porogen;

[0032] Figure 2 The inner layer structure diagram of the nerve repair conduit provided by the present invention when the salt is a porogen;

[0033] Figure 3 A schematic diagram of a nerve repair catheter provided by the present invention with a plurality of positioning holes at both ends;

[0034] Figure 4 A schematic diagram of a nerve repair catheter provided by the present invention with annular grooves or annular protrusions at both ends;

[0035] Figure 5 A schematic diagram of a nerve repair catheter provided by the present invention whose fixing structure is a spike. DETAILED DESCRIPTION

[0036] The technical solution of the present invention will be clearly and completely described below in conjunction with the embodiments. Obviously, the described embodiments are part of the embodiments of the present invention, rather than all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0037] According to one aspect of the present invention, a nerve repair catheter is mainly prepared from a biodegradable material by a casting method, wherein:

[0038] The outer surface of the nerve repair catheter has a grooved structure;

[0039] And / or, the inner surface of the nerve repair conduit has a growth guiding structure.

[0040] The nerve repair catheter provided by the present application is mainly prepared by a casting method using a biodegradable material, wherein: the outer surface of the nerve repair catheter has a grooved structure, and the grooved structure can allow a large amount of muscle and vascular tissue to grow in large quantities along the outer surface grooves of the catheter, which is conducive to rapid tissue growth and repair; at the same time, the inner surface of the nerve repair catheter also has a growth guide structure, such as longitudinal parallel grooves, which can be used to guide nerve growth, which is conducive to directional guidance of the proximal newborn nerve bundle to the corresponding distal target area, thereby improving the accuracy of nerve repair. Therefore, the nerve repair catheter of the present application has a better nerve defect repair effect as a nerve defect repair body.

[0041] Regarding nerve catheters, this application also needs to explain the length of nerve repair catheters:

[0042] When the distance of the nerve defect is short, especially less than 5mm, the axon can regenerate spontaneously. In the prior art, it is generally believed that the defect that can be bridged by an inert nerve conduit without any exogenous growth factors does not exceed 10mm; the defect that can be bridged by a polymer synthetic material nerve conduit with the addition of exogenous growth factors does not exceed 30mm. The longer the distance of the nerve defect, the more difficult it is to contact and guide. Therefore, there must be a limit to the defect that can be bridged by a nerve conduit. At present, the nerve conduits in the prior art are basically suitable for bridging nerve defects below 30mm.

[0043] At the same time, according to common clinical needs, the nerve repair catheter can be made into different lengths and specifications and used directly during surgery; the nerve repair catheter can also be made into a longer length and cut for use as needed.

[0044] (1) Length range for direct use without cutting: The length range of the nerve repair catheter of the present invention is 3-70 mm. Because the clinical significance of less than 3 mm is not great; for nerve defects greater than 70 mm, even if a nerve catheter is used, it is difficult to repair the defect, and it will play a role similar to that of a nerve cap, that is, it plays a role in protecting the stump to prevent it from further deterioration. Considering the effect of nerve repair, the preferred length range of the nerve repair catheter is 5-50 mm.

[0045] (2) Use after cutting: It can also be larger than 70mm and can be cut as needed.

[0046] At the same time, it should be noted that the inner diameter of the nerve repair catheter needs to be designed according to the diameter of the autologous nerve. The sciatic nerve is relatively thick among the autologous nerves, with a diameter of nearly 10mm; the diameter of the general diameter is about 2-3mm, such as: femoral nerve, tibial nerve, common peroneal nerve, radial nerve, ulnar nerve, median nerve, etc.; the diameter of the nerve is 1-2mm, such as axillary nerve, musculocutaneous nerve, lateral brachial cutaneous nerve, lateral forearm cutaneous nerve, medial brachial cutaneous nerve, medial forearm cutaneous nerve, anterior branch of radial nerve, posterior branch, lateral femoral cutaneous nerve, obturator nerve, saphenous nerve, etc.

[0047] In a preferred embodiment of the present invention, the nerve repair catheter comprises a single-layer structure nerve repair catheter or a multi-layer structure nerve repair catheter;

[0048] Preferably, the multi-layer structure nerve repair catheter includes a double-layer structure nerve repair catheter or a triple-layer structure nerve repair catheter.

[0049] As a preferred embodiment, the nerve repair catheter can be a single-layer, double-layer or three-layer structure; specifically:

[0050] (A) The single-layer structure of the nerve repair catheter is tubular.

[0051] Total thickness: 0.1-1.5mm; (This thickness range can meet the biomechanical properties of the nerve repair catheter and match the thickness of the human body's own nerves.) The inner diameter of the single-layer nerve repair catheter is designed according to the diameter of the autologous nerve. The inner diameter of the catheter is slightly larger than the outer diameter of the autologous nerve, which is convenient for inserting the autologous nerve stump into one end of the nerve repair catheter. The inner diameter of the nerve repair catheter is 1-15mm.

[0052] The pore size of the single-layer nerve repair catheter is 0-30μm. The single-layer nerve repair catheter does not need to have holes; if holes are made, the pore size cannot be too large, and the nerve repair catheter needs to have a certain mechanical strength and can play a supporting role; the holes can facilitate the flow of oxygen and nutrients, promote nerve growth, and at the same time prevent fibroblasts, inflammatory cells, muscle and vascular tissue cells from invading the lumen of the nerve repair catheter. The lumen of the nerve repair catheter provides space for the growth of nerve cells and provides a guiding growth function.

[0053] The outer surface of the single-layer nerve repair catheter provides attachment points for tissue cells and promotes their growth; the inner surface of the single-layer nerve repair catheter provides attachment points for nerve cells and promotes their growth.

[0054] (ii) The double-layer structure of the nerve repair catheter is tubular. There are two design situations for the inner diameter and outer diameter range of the double-layer structure.

[0055] Situation 1: The outer surface of the inner layer is in close contact with the inner surface of the outer layer.

[0056] The inner diameter of the inner layer is 1-15mm, which is the same as the inner diameter range of the single-layer nerve repair catheter. It is designed according to the diameter of the autologous nerve; at the same time, in order to facilitate the insertion of the autologous nerve stump into one end of the nerve repair catheter, the inner diameter of the catheter is slightly larger than the outer diameter of the autologous nerve. The thickness of the inner layer: 0.08-1.5mm, the pore diameter: 30-200um at the largest.

[0057] The structure of the inner layer varies depending on the porogen selected during production.

[0058] Figure 1 The inner structure of the nerve repair conduit when sugar is used as a porogen;

[0059] Figure 2 This is a diagram of the inner layer structure of the nerve repair catheter when salt is used as a porogen. When salt is used as a porogen, the inner layer structure presents a honeycomb-like porous structure. When this porous structure is used, the nerve repair speed is much faster than that of the previous inner layer structure.

[0060] The inner diameter of the outer layer is 1.3-16.5mm, the thickness of the outer layer is 0.1-1.5mm, and the pore size is 0-30um at the smallest point. The outer layer has a dense structure and can prevent fibroblasts, inflammatory cells, muscle and vascular tissue cells from invading the lumen of the nerve repair catheter. The lumen of the nerve repair catheter provides space for the growth of nerve cells and provides a guiding growth function. At the same time, if there are holes in the outer layer, and the holes are not very large, and the size of the holes in the outer layer is not enough to allow fibroblasts, inflammatory cells, muscle and vascular tissue cells to invade the lumen of the nerve repair catheter, it will also play a role in allowing a certain amount of oxygen and nutrients to enter the inner layer.

[0061] The outer layer provides attachment points for tissue cells and promotes tissue growth; the inner layer provides attachment points for nerve cells and promotes nerve growth.

[0062] Situation 2: The inner outer surface of the two ends of the catheter is layered with the outer inner surface, which is convenient for inserting the autologous nerve stump, and the inner outer surface of the remaining part is tightly fitted with the outer inner surface.

[0063] It is designed according to the diameter of the autologous nerve; at the same time, in order to facilitate the insertion of the autologous nerve stump between the two layers of the nerve repair catheter, the inner diameter of the catheter should be slightly larger than the outer diameter of the inner layer of the autologous nerve.

[0064] The inner diameter of the outer layer is 1.1-16mm, the thickness is 0.1-1.5mm, and the pore size is 0-30um at the smallest point.

[0065] The inner diameter of the inner layer is 0.8-14.5mm, the thickness is 0.08-1.5mm, and the pore size is 30-200um (a honeycomb-like porous structure).

[0066] The outer layer provides attachment points for tissue cells and promotes tissue growth; the inner layer provides attachment points for nerve cells and promotes nerve growth.

[0067] (III) Three-layer structure of nerve repair catheter: It is tubular, with the outer surface of the inner layer tightly fitting with the inner surface of the middle layer, and the outer surface of the middle layer tightly fitting with the inner surface of the outer layer.

[0068] The inner diameter of the outer layer is 1.1-16mm, the thickness is 0.06-1.5mm, and the pore size is 0-30um.

[0069] The inner diameter of the middle layer is 1.0-16mm, the thickness is 0.08-1.5mm, and the pore size is 50-300um. The pore size is larger than that of the other two layers, which is convenient for the flow of nutrients.

[0070] The inner diameter of the inner layer is 0.8-14.5mm, the thickness is 0.06-1.5mm, and the pore size is 30-200um.

[0071] The autologous nerve stump is directly inserted into the innermost part of the nerve repair catheter. The outer layer provides attachment points for tissue cells to promote tissue growth; the inner layer provides attachment points for nerve cells to promote nerve growth.

[0072] In a preferred embodiment of the present invention, the inner layer of the multi-layered nerve repair catheter is a plurality of bundles of small tubes arranged in parallel.

[0073] Preferably, the inner diameter of the multiple bundles of small tubes is 0.8-14.5 mm, the thickness is 0.01-0.8 mm, and the pore size is 30-200 um.

[0074] As a preferred embodiment, compared with the three-layer structure, the thickness and pore size of the outer layer remain unchanged, and the thickness and pore size of the middle layer remain unchanged. The inner layer material is made into multiple tube bundles, among which:

[0075] The inner diameter of the outer layer is 1.1-20mm, the thickness is 0.06-1.5mm, and the pore size is 0-30um.

[0076] The inner diameter of the middle layer is 1.0-20mm, the thickness is 0.08-1.5mm, and the pore size is 50-300um. The pore size is larger than that of the other two layers, which is convenient for the flow of nutrients.

[0077] The inner layer is composed of multiple bundles of tubules arranged in parallel. The inner diameter of the tubules is 0.8-14.5mm, the thickness is 0.01-0.8mm, and the pore size is 30-200um. The nerve bundles grow in the tubules.

[0078] In a preferred embodiment of the present invention, the degradable biomaterial includes at least one of polylactic acid, polycaprolactone, polyhydroxyalkanoate, polybutylene succinate, polybutylene terephthalate-adipate-polybutylene terephthalate, polyvinyl alcohol, and polycarbonate.

[0079] In a preferred embodiment of the present invention, positioning structures or fixing structures are provided at both ends of the nerve repair catheter.

[0080] In a preferred embodiment of the present invention, the positioning structure includes at least one of a positioning hole, a positioning groove or a positioning protrusion;

[0081] Figure 3 A schematic diagram of a nerve repair catheter with a plurality of positioning holes at both ends;

[0082] Figure 4 A schematic diagram of a nerve repair catheter with annular grooves or annular protrusions at both ends;

[0083] In a preferred embodiment of the present invention, the fixing structure comprises at least one of a flare, a spike or a barb.

[0084] Figure 5 A schematic diagram of a nerve repair catheter with a spike as a fixing structure;

[0085] According to one aspect of the present invention, a method for preparing the above-mentioned nerve repair catheter comprises the following steps:

[0086] (a) dissolving a degradable biomaterial in a non-alcoholic polar solvent to obtain a solution A; then adding a porogen and stirring until the porogen is evenly distributed to obtain a pipe-making solution;

[0087] (b) immersing a cylindrical tube-making jig into the tube-making solution, so that a layer of the tube-making solution adheres to the surface of the tube-making jig, and then taking it out and letting it stand; then demolding and removing the solvent, and drying to obtain a nerve repair catheter;

[0088] Optionally, step (b) is repeated once to obtain a double-layer structure nerve repair catheter; or step (b) is repeated twice to obtain a three-layer structure nerve repair catheter.

[0089] The preparation method of the nerve repair catheter provided by the present invention comprises the following steps: firstly dissolving a degradable biomaterial in a non-alcoholic polar solvent, and then adding a porogen to prepare a tube-making solution; then immersing a cylindrical tube-making jig in the tube-making solution, so that a layer of the tube-making solution adheres to the surface of the tube-making jig, and then taking it out and letting it stand; then demolding and removing the solvent, and drying to prepare the nerve repair catheter; the preparation method adopts a tape casting method to prepare the nerve repair catheter, and has the advantages of simple processing technology and easy operation.

[0090] In a preferred embodiment of the present invention, the non-alcoholic polar solvent includes at least one of tetrahydrofuran, ethylene dichloride, dimethyl ether or N,N-dimethylformamide.

[0091] In a preferred embodiment of the present invention, the porogen includes at least one of sodium chloride, sucrose, gelatin balls, monosodium glutamate, modified cellulose, urea, polyethylene glycol, and polyvinyl pyrrolidone.

[0092] Preferably, the method for preparing a nerve repair conduit by a casting method comprises the following steps:

[0093] (I) Preparation of pipe-making solution: Dissolve the degradable biomaterial in a non-alcoholic polar solvent to prepare a degradable biomaterial solution with a concentration of 3%-70% (w / v). Then add the porogen and stir until the porogen is evenly distributed to obtain the pipe-making solution.

[0094] The porogen is sodium chloride, sucrose, gelatin balls, monosodium glutamate, modified cellulose, urea, polyethylene glycol, or polyvinyl pyrrolidone. Specific:

[0095] 1. Single layer:

[0096] The concentration range of the porogen is controlled at 0-500% (w / v). The particle size of the porogen is controlled at 0-29um. (When the porogen is in a solid state, it will expand and contract within a certain temperature range, especially sucrose.)

[0097] 2. Double layer:

[0098] Inner layer: The concentration range of the porogen is controlled at 0-500% (w / v). The particle size of the porogen is controlled at 29-199 um.

[0099] Outer layer: The concentration range of the porogen is controlled at 0-500% (w / v). The particle size of the porogen is controlled at 0-29 um.

[0100] 3. Three layers:

[0101] Outer layer: The concentration range of the porogen is controlled at 0-500% (w / v). The particle size of the porogen is controlled at 0-29 um.

[0102] Middle layer: The concentration range of the porogen is controlled at 0-500% (w / v). The particle size of the porogen is controlled at 49-299 um.

[0103] Inner layer: The concentration range of the porogen is controlled at 0-500% (w / v). The particle size of the porogen is controlled at 29-199um. The porogen is preferably 30-100um sodium chloride particles after grinding and sieving.

[0104] 4. Nerve repair catheter with a multi-bundle structure in cross section:

[0105] Outer layer: The concentration range of the porogen is controlled at 0-500% (w / v). The particle size of the porogen is controlled at 0-29 um.

[0106] Middle layer: The concentration range of the porogen is controlled at 0-500% (w / v). The particle size of the porogen is controlled at 49-299 um.

[0107] Inner layer: The concentration range of the porogen is controlled at 0-500% (w / v). The particle size of the porogen is controlled at 29-199um. The porogen is preferably 30-100um sodium chloride particles after grinding and sieving.

[0108] (ii) Pipe making: Immerse a cylindrical pipe making jig in the pipe making solution so that a layer of the pipe making solution adheres to the surface of the pipe making jig. Then, take it out of the pipe making solution and let it stand.

[0109] While standing still, the non-alcohol polar solvent in the tube-making solution attached to the surface of the tube-making jig continues to evaporate, and the initial product of the nerve repair catheter gradually takes shape.

[0110] 1. Making a single-layer nerve repair catheter:

[0111] A tube making solution is prepared to make the tube. The number of times the tube making jig is immersed, taken out and left to stand in the tube making step is adjusted according to the thickness requirement of the nerve repair catheter, that is, the thicker the nerve repair catheter is, the more times the jig is immersed, taken out and left to stand.

[0112] 2. Making double-layer or triple-layer nerve repair catheters:

[0113] According to the structural aperture requirements of different layers of the nerve repair catheter, a variety of tube making solutions are configured. The tube making fixture is immersed in and taken out of different tube making solutions in turn, and the number of immersion and removal in different tube making solutions is adjusted according to the thickness requirements of different layers.

[0114] 3. Making a nerve repair catheter with a multi-bundle structure:

[0115] (1) An inner tube body is manufactured by using a mold. After the inner tube body is formed, the inner tube body is immersed in the tube-making solution of the middle layer and the outer layer in turn to manufacture the middle layer and the outer layer.

[0116] (2) separately preparing a tube body of the outer layer + the middle layer; separately preparing a plurality of inner layer tube bodies; and inserting the plurality of inner layer tube bodies into the tube body of the outer layer + the middle layer in parallel.

[0117] (III) Demolding: peeling off the initial product of the nerve repair catheter from the above-mentioned tube making jig.

[0118] It can be directly peeled off (to facilitate direct peeling, structures such as protrusions or stripes can be provided on the surface of the fixture); it can also be peeled off after being immersed in glucose solution, pure water, water for injection or saline solution; it can also be easily peeled off by using a release agent such as polytetrafluoroethylene.

[0119] (iv) Removing the solvent: Immerse the initial product of the nerve repair catheter in glucose solution, pure water, water for injection or physiological saline until the non-alcoholic polar solvent is removed.

[0120] In the process of removing the non-alcoholic polar solvent, the porogen is also partially or completely removed. If it is partially removed, some porogens remain in the initial product of the nerve repair catheter, which does not affect the use of the nerve repair catheter in the human body. The total amount of residual non-alcoholic polar solvent is ≤ 0.1%.

[0121] (V) Drying: Dry the initial product of the nerve repair catheter until the residual moisture in the initial product of the nerve repair catheter is ≤ 0.5% for easy storage.

[0122] (VI) Post-processing: After drying, the rough edges or uneven thickness of the initial product of the nerve repair catheter are removed. Confirm that there are no bubbles, no damage, no foreign matter, and the thickness is uniform, and cut into the required size, which is the finished product of the nerve repair catheter.

[0123] At the same time, it should be noted that the advantages of the single-layer, double-layer, triple-layer or multi-bundle structure of the nerve repair catheter of the present application can be summarized as follows:

[0124] 1. One-layer structure: Dense structure (no holes or very small holes) is to prevent external fibroblasts, inflammatory cells, muscle and vascular tissue cells from growing into the lumen of the nerve conduit to hinder and inhibit nerve repair and growth.

[0125] When making holes, sufficient oxygen and nutrition are provided to the repair and growth of nerves in the catheter through numerous micropores.

[0126] 2. The structural advantage of double layer over single layer: adding an inner layer is conducive to the growth of nerve cells. There are two reasons. First, the porous structure of the inner layer (due to the different porogens selected during production, the morphology of the porous structure layer is different, among which the honeycomb porous structure made of salt is preferred, which has a faster nerve repair speed), which is convenient for nerve cell attachment and conducive to nerve cell growth; second, the holes in the inner layer facilitate the flow of oxygen and nutrients, which is conducive to the growth of nerve cells.

[0127] The double-layer outer structure is as dense as the single-layer structure and has the same function: supporting, ensuring the mechanical properties of the nerve repair catheter, blocking fibroblasts, inflammatory cells, muscle and vascular tissue cells from invading the lumen of the nerve repair catheter. The lumen of the nerve repair catheter provides space for the growth of nerve cells and provides a guiding growth function.

[0128] There are two designs of double layers. In addition to the above-mentioned beneficial effects, the second case has another beneficial effect: when the autologous nerve stump is inserted between the two layers of the nerve repair catheter, the nerve will grow along the direction between the two layers, and the guided growth effect is better than that of the first case.

[0129] When the outer layer is pore-formed, oxygen and nutrients can easily pass through the outer layer and flow into the inner layer.

[0130] 3. The structural advantage of three layers over two layers: adding a middle layer, the pore size of the middle layer is larger than that of the outer and inner layers, which facilitates the flow of nutrients and is beneficial to the growth of nerve cells.

[0131] 4. Advantages of multi-bundle structured nerve repair catheters: In addition to the beneficial effects of the outer and inner layers of the three-layer nerve repair catheter, because the inner layer is a multi-bundle tubule structure, the nerve bundles can be guided to grow in each bundle of tubules, which is conducive to directional guidance of the proximal newly generated nerve bundles to the corresponding distal target area, thereby improving the accuracy of nerve repair.

[0132] Example 1

[0133] A method for preparing a single-layer nerve repair conduit by a tape casting method comprises the following steps:

[0134] (1) Solution preparation: The polyurethane material is dissolved in tetrahydrofuran (THF) solvent to prepare 100 mL of a polyurethane solution with a concentration of 35% (w / v). Sodium chloride particles with a concentration of 250% (w / v) and a particle size of 10-20 μm after grinding and sieving are added, and the mixture is stirred until the sodium chloride particles are evenly distributed to obtain a pipe making solution.

[0135] (2) Pipe making: A cylindrical pipe making jig is immersed in the pipe making solution. After a layer of the pipe making solution adheres to the surface of the pipe making jig, the jig is taken out from the pipe making solution and allowed to stand.

[0136] While standing still, the tetrahydrofuran solvent in the tube-making solution attached to the surface of the tube-making jig evaporates continuously, and the initial product of the nerve repair catheter gradually takes shape.

[0137] (3) Demolding: Soak the above-mentioned tube-making jig in pure water until the initial product of the nerve repair catheter is peeled off from the above-mentioned tube-making jig.

[0138] (4) Removing the solvent: Immerse the initial product of the nerve repair catheter in pure water until the total amount of residual solvent in the initial product of the nerve repair catheter is ≤0.1% and the porosity is 0-200%.

[0139] (5) Drying: Dry the initial product of the nerve repair catheter until the residual moisture in the initial product of the nerve repair catheter is ≤ 0.5% for easy storage.

[0140] (6) Post-processing: After drying, remove the rough edges or uneven thickness of the initial product of the nerve repair catheter. Make sure there are no bubbles, no damage, no foreign matter, and the thickness is uniform, and cut it into the required size. Sterilize it with cobalt 60-γ rays, package it and store it, and it will be the finished product of the nerve repair catheter.

[0141] The specific test method for the performance test of the nerve repair catheter in this embodiment is as follows:

[0142] 1. Moisture residue test method: Before the test, place the hernia repair patch sample in a drying device to dry it, then adjust the trace moisture meter to the test parameters, measure the moisture content of the dry hernia repair patch, wait for the system to complete the sample analysis, record the experimental data, and test the next sample.

[0143] 2. Porosity test method: Cut the dry hernia repair patch into specified sizes as required, use thickness gauge, density balance and other measuring instruments to measure the length, width, thickness, mass and other parameters of the sample, then use the hexadecane absorption method to determine the sample mass, and finally use the porosity formula to obtain the porosity experimental value.

[0144] 3. Solvent residue test method: Use a gas chromatograph and select appropriate mobile phase, water phase, injection temperature and headspace injector test conditions according to product requirements. Weigh the dry hernia repair patch sample and dissolve it in the solvent to prepare the test solution. Then adjust the injection conditions for testing.

[0145] 4. Thickness test method: First use a measuring tool to cut a good quality dry hernia repair patch sample, then use a thickness gauge to test the sample thickness, repeat the measurement multiple times and take the average value.

[0146] 5. Tensile strength test method: First, cut the dry hernia repair patch sample to be tested into multiple specimens with appropriate width, flat edges, parallel sides and no visible defects, then turn on the tensile testing machine, set the parameters, and perform tensile testing. And perform data processing.

[0147] 6. Suture strength test method: first cut the dry hernia repair patch samples to be tested into multiple samples with appropriate width, flat edges, parallel sides and no visible defects, then use the selected specification of suture thread to sew with two needles at one end of the sample to be tested and tie a knot to fix it, sew multiple patch samples in the same way, and test the thickness of each sample with a thickness gauge, and then use a tensile testing machine to clamp the sample to be tested to test the suture strength of the suture to obtain the test data.

[0148] 7. Bursting strength test method: first cut the dry hernia repair patch sample to be tested into multiple square specimens with appropriate width, flat edges, parallel sides and no visible defects, and use a thickness gauge to test the thickness of each sample. Then turn on the tensile testing machine, clamp the sample to be tested, perform the bursting strength test, and obtain the test data.

[0149] 8. Tear strength test method: first cut the dry hernia repair patch sample to be tested into multiple samples with appropriate width, flat edges, parallel sides and no visible defects, and use a thickness gauge to test the quality of each sample. Then use a cutter to cut along the center of the sample to prepare a trouser-type sample. The edge of the cutter must be kept sharp without curling or notches. Turn on the tensile testing machine, clamp the sample to be tested, perform a tear strength test, and obtain the test data.

[0150] The test results are shown in the following table:

[0151] Table: Single-layer nerve repair catheter test results

[0152]

[0153]

[0154] Example 2

[0155] A method for preparing a double-layer nerve conduit by a tape casting method comprises the following steps:

[0156] (1) Dissolving the polyurethane material: The polyurethane material was dissolved in tetrahydrofuran (THF) solvent to prepare 100 ml of polyurethane solutions with concentrations of 35% (w / v) and 35% (w / v).

[0157] (2) Preparation of Solution 1: Grind sodium chloride and sieve out sodium chloride with a particle size of 100 μm using a sieve. The sodium chloride concentration is 250% (w / v). Add it to the prepared 35% polyurethane material solution and stir it with a magnetic force until the sodium chloride is evenly dispersed in the solution to prepare Solution 1.

[0158] (3) Preparation of Solution 2: Grind sodium chloride and sieve out sodium chloride with a particle size of 15 μm using a sieve. The sodium chloride concentration is 250% (w / v). Add it to the prepared 35% biodegradable biomaterial solution and stir with a magnetic force until the sodium chloride is evenly dispersed in the solution to prepare Solution 2.

[0159] (4) Making a large-pore inner tube: insert a cylindrical tube-making jig vertically into the solution 1 and let it stand for 5 seconds so that a layer of the tube-making solution 1 adheres to the surface of the tube-making jig. Take out the tube-making jig and let it stand for 10 minutes.

[0160] (5) Preparation of microporous outer tube: After standing for 10 minutes in the above step, vertically insert the mold into solution 2 and stand for 5 seconds, so that the surface of the tube making jig is completely covered with a layer of tube making solution 2. Take out the mold and stand for 10 minutes.

[0161] While standing still, the tetrahydrofuran solvent in the tube-making solution attached to the surface of the tube-making jig evaporates continuously, and the initial product of the nerve repair catheter gradually takes shape.

[0162] (6) Demolding: Soak the above-mentioned tube-making jig in pure water until the initial product of the nerve repair catheter is peeled off from the above-mentioned tube-making jig.

[0163] (7) Removing the solvent: Immerse the initial product of the nerve repair catheter in pure water until the total amount of residual solvent in the initial product of the nerve repair catheter is ≤0.1% and the porosity is 0-200%.

[0164] (8) Drying: Dry the initial product of the nerve repair catheter until the residual moisture in the initial product of the nerve repair catheter is ≤ 0.5% for easy storage.

[0165] (9) Post-processing: After drying, remove the rough edges or uneven thickness of the initial product of the nerve repair catheter. Make sure there are no bubbles, no damage, no foreign matter, and the thickness is uniform, and then cut it into the required size. Sterilize it with cobalt 60-γ rays, package it and store it, and it will be the finished product of the nerve repair catheter.

[0166] The performance test of the nerve repair catheter in this embodiment is carried out in the same manner as in Example 1.

[0167] The test results are shown in the following table:

[0168] Table: Test results of layer nerve repair catheter

[0169]

[0170] Example 3

[0171] A method for preparing a three-layer nerve conduit by a tape casting method comprises the following steps:

[0172] (1) Dissolving the polyurethane material: Dissolve the polyurethane material in tetrahydrofuran (THF) to prepare 100 ml of each of the polyurethane material solutions with concentrations of 35% (w / v), 35% (w / v), and 35% (w / v).

[0173] (2) Preparation of Solution 1: Grind sodium chloride and sieve out sodium chloride with a particle size of 100 μm using a sieve. The sodium chloride concentration is 250% (w / v). Add it to the prepared polyurethane solution with a concentration of 35%, and stir with a magnetic force until the sodium chloride is evenly dispersed in the solution to prepare Solution 1.

[0174] (3) Preparation of Solution 2: Grind sodium chloride and sieve out sodium chloride with a particle size of 250 μm using a sieve. The sodium chloride concentration is 250% (w / v). Add the sodium chloride to the prepared polyurethane solution with a concentration of 35%, and stir with a magnetic force until the sodium chloride is evenly dispersed in the solution to prepare Solution 2.

[0175] (4) Preparation of Solution 3: Grind sodium chloride and sieve out sodium chloride with a particle size of 15 μm. The sodium chloride concentration is 250% (w / v). Add it to the prepared polyurethane solution with a concentration of 35%, and stir with a magnetic force until the sodium chloride is evenly dispersed in the solution to prepare Solution 3.

[0176] (5) Making a middle-hole inner tube: insert a cylindrical tube-making jig vertically into the solution 1 and let it stand for 5 seconds so that a layer of the tube-making solution 1 adheres to the surface of the tube-making jig. Take out the tube-making jig and let it stand for 10 minutes.

[0177] (6) Making a large-pore transition layer tube: After the tube making jig has been left to stand for 10 minutes in the previous step, vertically insert it into Solution 2 and let it stand for 5 seconds, so that Solution 2 completely covers the surface of the mold. Take out the mold and let it stand for 10 minutes.

[0178] (7) Preparation of microporous outer tube: After the tube preparation jig has been left to stand for 10 minutes in the previous step, vertically insert it into solution 3 and let it stand for 5 seconds, so that the surface of the jig is completely covered by solution 3. Take out the jig and let it stand for 10 minutes.

[0179] While standing still, the tetrahydrofuran solvent in the tube-making solution attached to the surface of the tube-making jig evaporates continuously, and the initial product of the nerve repair catheter gradually takes shape.

[0180] (8) Demolding, solvent removal, drying, and post-treatment steps: the same as in Example 1.

[0181] The performance test of the nerve repair catheter in this embodiment is carried out in the same manner as in Example 1.

[0182] The test results are shown in the following table:

[0183] Table: Test results of three-layer nerve repair catheter

[0184]

[0185] Example 4: Making nerve repair catheters using different biodegradable materials

[0186] 4-1: A method for preparing a three-layer nerve conduit using polylactic acid biodegradable material, comprising the following steps:

[0187] (1) Dissolving polylactic acid material: dissolve polylactic acid material in dimethyl ether (DME) to prepare 100 ml of polyurethane material solution with concentrations of 35% (w / v), 35% (w / v), and 35% (w / v).

[0188] (2) Preparation of Solution 1: Grind sodium chloride and sieve out sodium chloride with a particle size of 100 μm using a sieve. The sodium chloride concentration is 250% (w / v). Add the sodium chloride to the prepared polylactic acid material solution with a concentration of 35%, and stir with a magnetic force until the sodium chloride is evenly dispersed in the solution to prepare Solution 1.

[0189] (3) Preparation of Solution 2: Grind sodium chloride and sieve out sodium chloride with a particle size of 250 μm using a sieve. The sodium chloride concentration is 250% (w / v). Add the sodium chloride to the prepared polylactic acid solution with a concentration of 35%, and stir with a magnetic force until the sodium chloride is evenly dispersed in the solution to prepare Solution 2.

[0190] (4) Preparation of Solution 3: Grind sodium chloride and sieve out sodium chloride with a particle size of 15 μm using a sieve. The sodium chloride concentration is 250% (w / v). Add the sodium chloride to the prepared polylactic acid solution with a concentration of 35%, and stir with a magnetic force until the sodium chloride is evenly dispersed in the solution to prepare Solution 3.

[0191] (5) Making a middle-hole inner tube: insert a cylindrical tube-making jig vertically into the solution 1 and let it stand for 5 seconds so that a layer of the tube-making solution 1 adheres to the surface of the tube-making jig. Take out the tube-making jig and let it stand for 10 minutes.

[0192] (6) Making a large-pore transition layer tube: After the tube making jig has been left to stand for 10 minutes in the previous step, vertically insert it into Solution 2 and let it stand for 5 seconds, so that Solution 2 completely covers the surface of the jig. Take out the mold and let it stand for 10 minutes.

[0193] (7) Preparation of microporous outer tube: After the jig has been left to stand for 10 minutes in the previous step, vertically insert it into solution 3 and leave it to stand for 5 seconds, so that the surface of the jig is completely covered by solution 3. Take out the jig and leave it to stand for 10 minutes.

[0194] While standing still, the tetrahydrofuran solvent in the tube-making solution attached to the surface of the tube-making jig evaporates continuously, and the initial product of the nerve repair catheter gradually takes shape.

[0195] (8) Demolding, solvent removal, drying, and post-treatment steps: the same as in Example 1.

[0196] The performance test of the nerve repair catheter in this embodiment is carried out in the same manner as in Example 1.

[0197] The test results are shown in the following table:

[0198] Table: Test results of nerve repair catheters made of polylactic acid

[0199]

[0200] 4-2: A method for preparing a three-layer nerve conduit using a polyhydroxyalkanoate biodegradable material, comprising the following steps:

[0201] (1) Dissolving the polyhydroxyalkanoate material: The polyhydroxyalkanoate material was dissolved in dimethyl ether (DME) to prepare 100 ml of each of 35% (w / v), 35% (w / v), and 35% (w / v) polyurethane material solutions.

[0202] (2) Preparation of Solution 1: Grind sodium chloride and sieve out sodium chloride with a particle size of 100 μm using a sieve. The sodium chloride concentration is 250% (w / v). Add the sodium chloride to the prepared polyhydroxyalkanoate material solution with a concentration of 35%, and stir with a magnetic force until the sodium chloride is evenly dispersed in the solution to prepare Solution 1.

[0203] (3) Preparation of Solution 2: Grind sodium chloride and sieve out sodium chloride with a particle size of 250 μm using a sieve. The sodium chloride concentration is 250% (w / v). Add the sodium chloride to the prepared polyhydroxyalkanoate solution with a concentration of 35%, and stir with a magnetic force until the sodium chloride is evenly dispersed in the solution to prepare Solution 2.

[0204] (4) Preparation of Solution 3: Grind sodium chloride and sieve out sodium chloride with a particle size of 15 μm. The sodium chloride concentration is 250% (w / v). Add the sodium chloride to the prepared polyhydroxyalkanoate solution with a concentration of 35%, and stir with a magnetic force until the sodium chloride is evenly dispersed in the solution to prepare Solution 3.

[0205] (5) Making a middle-hole inner tube: insert a cylindrical tube-making jig vertically into the solution 1 and let it stand for 5 seconds so that a layer of the tube-making solution 1 adheres to the surface of the tube-making jig. Take out the tube-making jig and let it stand for 10 minutes.

[0206] (6) Making a large-pore transition layer tube: After the tube making jig has been left to stand for 10 minutes in the previous step, vertically insert it into Solution 2 and let it stand for 5 seconds, so that Solution 2 completely covers the surface of the jig. Take out the mold and let it stand for 10 minutes.

[0207] (7) Preparation of microporous outer tube: After the jig has been left to stand for 10 minutes in the previous step, vertically insert it into solution 3 and leave it to stand for 5 seconds, so that the surface of the jig is completely covered by solution 3. Take out the jig and leave it to stand for 10 minutes.

[0208] While standing still, the tetrahydrofuran solvent in the tube-making solution attached to the surface of the tube-making jig evaporates continuously, and the initial product of the nerve repair catheter gradually takes shape.

[0209] (8) Demolding, solvent removal, drying, and post-treatment steps: the same as in Example 1.

[0210] The performance test of the nerve repair catheter in this embodiment is carried out in the same manner as in Example 1.

[0211] The test results are shown in the following table:

[0212] Table: Test results of nerve repair catheters made of polyhydroxyalkanoate materials

[0213]

[0214] 4-3: A method for preparing a three-layer nerve conduit using polybutylene succinate biodegradable material, comprising the following steps:

[0215] (1) Dissolving polybutylene succinate material: dissolve polybutylene succinate material in dimethyl ether (DME) to prepare 100 ml of polybutylene succinate material solution with concentrations of 35% (w / v), 35% (w / v), and 35% (w / v).

[0216] (2) Preparation of Solution 1: Grind sodium chloride and sieve out sodium chloride with a particle size of 100 μm using a sieve. The sodium chloride concentration is 250% (w / v). Add the sodium chloride to the prepared polybutylene succinate material solution with a concentration of 35%, and stir with a magnetic force until the sodium chloride is evenly dispersed in the solution to prepare Solution 1.

[0217] (3) Preparation of Solution 2: Grind sodium chloride and sieve out sodium chloride with a particle size of 250 μm using a sieve. The sodium chloride concentration is 250% (w / v). Add the sodium chloride to the prepared polybutylene succinate solution with a concentration of 35%, and stir with a magnetic force until the sodium chloride is evenly dispersed in the solution to prepare Solution 2.

[0218] (4) Preparation of Solution 3: Grind sodium chloride and sieve out sodium chloride with a particle size of 15 μm using a sieve. The sodium chloride concentration is 250% (w / v). Add the sodium chloride to the prepared polybutylene succinate solution with a concentration of 35%, and stir with a magnetic force until the sodium chloride is evenly dispersed in the solution to prepare Solution 3.

[0219] (5) Making a middle-hole inner tube: insert a cylindrical tube-making jig vertically into the solution 1 and let it stand for 5 seconds so that a layer of the tube-making solution 1 adheres to the surface of the tube-making jig. Take out the tube-making jig and let it stand for 10 minutes.

[0220] (6) Making a large-pore transition layer tube: After the tube making jig has been left to stand for 10 minutes in the previous step, vertically insert it into Solution 2 and let it stand for 5 seconds, so that Solution 2 completely covers the surface of the jig. Take out the mold and let it stand for 10 minutes.

[0221] (7) Preparation of microporous outer tube: After the jig has been left to stand for 10 minutes in the previous step, vertically insert it into solution 3 and leave it to stand for 5 seconds, so that the surface of the jig is completely covered by solution 3. Take out the jig and leave it to stand for 10 minutes.

[0222] While standing still, the tetrahydrofuran solvent in the tube-making solution attached to the surface of the tube-making jig evaporates continuously, and the initial product of the nerve repair catheter gradually takes shape.

[0223] (8) Demolding, solvent removal, drying, and post-treatment steps: the same as in Example 1.

[0224] The performance test of the nerve repair catheter in this embodiment is carried out in the same manner as in Example 1.

[0225] The test results are shown in the following table:

[0226] Table: Test results of nerve repair catheters made of polybutylene succinate material

[0227]

[0228]

[0229] 4-4: A method for preparing a three-layer nerve conduit using a biodegradable poly(butylene terephthalate-adipate) biodegradable material, comprising the following steps:

[0230] (1) Dissolving poly(butylene terephthalate)-adipate material: Dissolve the poly(butylene terephthalate)-adipate material in dimethyl ether (DME) to prepare 100 ml of each poly(butylene terephthalate)-adipate material solution with a concentration of 35% (w / v), 35% (w / v), and 35% (w / v).

[0231] (2) Preparation of Solution 1: Grind sodium chloride and sieve out sodium chloride with a particle size of 100 μm using a sieve. The sodium chloride concentration is 250% (w / v). Add the sodium chloride to the prepared poly(butylene terephthalate-adipate-glycol) material solution with a concentration of 35%, and stir with a magnetic force until the sodium chloride is evenly dispersed in the solution to prepare Solution 1.

[0232] (3) Preparation of Solution 2: Grind sodium chloride and sieve out sodium chloride with a particle size of 250 μm using a sieve. The sodium chloride concentration is 250% (w / v). Add the sodium chloride to the prepared polybutylene terephthalate-adipate-glycol solution with a concentration of 35%, and stir with a magnetic force until the sodium chloride is evenly dispersed in the solution to prepare Solution 2.

[0233] (4) Preparation of Solution 3: Grind sodium chloride and sieve out sodium chloride with a particle size of 15 μm. The sodium chloride concentration is 250% (w / v). Add the sodium chloride to the prepared polybutylene terephthalate-adipate-glycol solution with a concentration of 35%, and stir with a magnetic force until the sodium chloride is evenly dispersed in the solution to prepare Solution 3.

[0234] (5) Making a middle-hole inner tube: insert a cylindrical tube-making jig vertically into the solution 1 and let it stand for 5 seconds so that a layer of the tube-making solution 1 adheres to the surface of the tube-making jig. Take out the tube-making jig and let it stand for 10 minutes.

[0235] (6) Making a large-pore transition layer tube: After the tube making jig has been left to stand for 10 minutes in the previous step, vertically insert it into Solution 2 and let it stand for 5 seconds, so that Solution 2 completely covers the surface of the jig. Take out the mold and let it stand for 10 minutes.

[0236] (7) Preparation of microporous outer tube: After the jig has been left to stand for 10 minutes in the previous step, vertically insert it into solution 3 and leave it to stand for 5 seconds, so that the surface of the jig is completely covered by solution 3. Take out the jig and leave it to stand for 10 minutes.

[0237] While standing still, the tetrahydrofuran solvent in the tube-making solution attached to the surface of the tube-making jig evaporates continuously, and the initial product of the nerve repair catheter gradually takes shape.

[0238] (8) Demolding, solvent removal, drying, and post-treatment steps: the same as in Example 1.

[0239] The performance test of the nerve repair catheter in this embodiment is carried out in the same manner as in Example 1.

[0240] The test results are shown in the following table:

[0241] Table: Test results of nerve repair catheters made of polybutylene terephthalate-adipate material

[0242]

[0243] 4-5: A method for preparing a three-layer nerve conduit using polyvinyl alcohol biodegradable material, comprising the following steps:

[0244] (1) Dissolving the polyvinyl alcohol material: dissolve the polyvinyl alcohol material in dimethyl ether (DME) to prepare 100 ml of each polyvinyl alcohol material solution with a concentration of 35% (w / v), 35% (w / v), and 35% (w / v).

[0245] (2) Preparation of Solution 1: Grind sodium chloride and sieve out sodium chloride with a particle size of 100 μm using a sieve. The sodium chloride concentration is 250% (w / v). Add the sodium chloride to the prepared polyvinyl alcohol material solution with a concentration of 35%, and stir with a magnetic force until the sodium chloride is evenly dispersed in the solution to prepare Solution 1.

[0246] (3) Preparation of Solution 2: Grind sodium chloride and sieve out sodium chloride with a particle size of 250 μm using a sieve. The sodium chloride concentration is 250% (w / v). Add the sodium chloride to the prepared polyvinyl alcohol solution with a concentration of 35%, and stir with a magnetic force until the sodium chloride is evenly dispersed in the solution to prepare Solution 2.

[0247] (4) Preparation of Solution 3: Grind sodium chloride and sieve out sodium chloride with a particle size of 15 μm using a sieve. The sodium chloride concentration is 250% (w / v). Add the sodium chloride to the prepared polyvinyl alcohol solution with a concentration of 35%, and stir with a magnetic force until the sodium chloride is evenly dispersed in the solution to prepare Solution 3.

[0248] (5) Making a middle-hole inner tube: insert a cylindrical tube-making jig vertically into the solution 1 and let it stand for 5 seconds so that a layer of the tube-making solution 1 adheres to the surface of the tube-making jig. Take out the tube-making jig and let it stand for 10 minutes.

[0249] (6) Making a large-pore transition layer tube: After the tube making jig has been left to stand for 10 minutes in the previous step, vertically insert it into Solution 2 and let it stand for 5 seconds, so that Solution 2 completely covers the surface of the jig. Take out the mold and let it stand for 10 minutes.

[0250] (7) Preparation of microporous outer tube: After the jig has been left to stand for 10 minutes in the previous step, vertically insert it into solution 3 and leave it to stand for 5 seconds, so that the surface of the jig is completely covered by solution 3. Take out the jig and leave it to stand for 10 minutes.

[0251] While standing still, the tetrahydrofuran solvent in the tube-making solution attached to the surface of the tube-making jig evaporates continuously, and the initial product of the nerve repair catheter gradually takes shape.

[0252] (8) Demolding, solvent removal, drying, and post-treatment steps: the same as in Example 1.

[0253] The performance test of the nerve repair catheter in this embodiment is carried out in the same manner as in Example 1.

[0254] The test results are shown in the following table:

[0255] Table: Test results of nerve repair catheters made of polyvinyl alcohol

[0256]

[0257] 4-6: A method for preparing a three-layer nerve conduit using a polycarbonate biodegradable material, comprising the following steps:

[0258] (1) Dissolving polycarbonate material: dissolving the polycarbonate material in dimethyl ether (DME) solvent to prepare 100 ml of polycarbonate material solutions with concentrations of 35% (w / v), 35% (w / v), and 35% (w / v).

[0259] (2) Preparation of Solution 1: Grind sodium chloride and sieve out sodium chloride with a particle size of 100 μm using a sieve. The sodium chloride concentration is 250% (w / v). Add it to the prepared polycarbonate material solution with a concentration of 35%, and stir with a magnetic force until the sodium chloride is evenly dispersed in the solution to prepare Solution 1.

[0260] (3) Preparation of Solution 2: Grind sodium chloride and sieve out sodium chloride with a particle size of 250 μm using a sieve. The sodium chloride concentration is 250% (w / v). Add the sodium chloride to the prepared polycarbonate solution with a concentration of 35%, and stir with a magnetic force until the sodium chloride is evenly dispersed in the solution to prepare Solution 2.

[0261] (4) Preparation of Solution 3: Grind sodium chloride and sieve out sodium chloride with a particle size of 15 μm using a sieve. The sodium chloride concentration is 250% (w / v). Add the sodium chloride to the prepared polycarbonate solution with a concentration of 35%, and stir with a magnetic force until the sodium chloride is evenly dispersed in the solution to prepare Solution 3.

[0262] (5) Making a middle-hole inner tube: insert a cylindrical tube-making jig vertically into the solution 1 and let it stand for 5 seconds so that a layer of the tube-making solution 1 adheres to the surface of the tube-making jig. Take out the tube-making jig and let it stand for 10 minutes.

[0263] (6) Making a large-pore transition layer tube: After the tube making jig has been left to stand for 10 minutes in the previous step, vertically insert it into Solution 2 and let it stand for 5 seconds, so that Solution 2 completely covers the surface of the jig. Take out the mold and let it stand for 10 minutes.

[0264] (7) Preparation of microporous outer tube: After the jig has been left to stand for 10 minutes in the previous step, vertically insert it into solution 3 and leave it to stand for 5 seconds, so that the surface of the jig is completely covered by solution 3. Take out the jig and leave it to stand for 10 minutes.

[0265] While standing still, the tetrahydrofuran solvent in the tube-making solution attached to the surface of the tube-making jig evaporates continuously, and the initial product of the nerve repair catheter gradually takes shape.

[0266] (8) Demolding, solvent removal, drying, and post-treatment steps: the same as in Example 1.

[0267] The performance test of the nerve repair catheter in this embodiment is carried out in the same manner as in Example 1.

[0268] The test results are shown in the following table:

[0269] Table: Test results of nerve repair catheters made of polycarbonate materials

[0270]

[0271]

[0272] Example 5 uses non-alcohol polar solvents of different concentrations to illustrate the effect of non-alcohol polar solvent concentration on the performance of nerve repair catheters:

[0273] A method for preparing a single-layer nerve repair catheter using polyurethane biodegradable material comprises the following steps:

[0274] (1) Preparation of pipe making solution: The polyurethane biodegradable biomaterial was dissolved in the tetrahydrofuran solvents shown in the table below to prepare 100 mL of polyurethane solution with concentrations of 5% (w / v), 10% (w / v), 15% (w / v), and 20% (w / v), respectively.

[0275] Then, add ground and sieved sodium chloride particles with a concentration of 250% (w / v) and a particle size of 10-20 μm, and stir until the sodium chloride particles are evenly distributed to obtain a pipe making solution.

[0276] (2) Tube making: The cylindrical tube making jigs are immersed in the above-mentioned tube making solutions of different concentrations to prepare a plurality of nerve repair conduits. After the surface of the tube making jig is completely covered with a layer of the tube making solution, the jigs are taken out from the tube making solution and allowed to stand.

[0277] While standing still, the tetrahydrofuran solvent in the tube-making solution attached to the surface of the tube-making jig evaporates continuously, and the initial product of the nerve repair catheter gradually takes shape.

[0278] (3) Demolding, solvent removal, drying, and post-treatment steps: the same as in Example 1.

[0279] The performance test of the nerve repair catheter in this embodiment is carried out in the same manner as in Example 1.

[0280] The test results are shown in the following table:

[0281] Table: Comparative experiments with different solvent concentrations

[0282]

[0283]

[0284] It can be seen from the above table that under the same conditions, the less solvent, the thicker the tube wall and the better the mechanical properties. Example 6: Single-layer nerve repair conduits were prepared using different porogen concentrations to illustrate the effect of porogen concentration on the performance of nerve repair conduits.

[0285] A method for preparing a single-layer nerve repair catheter using polyurethane biodegradable material comprises the following steps:

[0286] (1) Preparation of pipe making solution: The polyurethane biodegradable biomaterial was dissolved in the tetrahydrofuran solvents shown in the following table to prepare 100 mL of polyurethane solution with a concentration of 35% (w / v).

[0287] Then add ground and sieved sodium chloride particles with a concentration of 0% (w / v), 10% (w / v), 40% (w / v), and 60% (w / v), with a particle size of 10-20 μm, and stir until the sodium chloride particles are evenly distributed. Then, a variety of tube-making solutions can be prepared to make multiple nerve repair catheters.

[0288] (2) Tube making: The cylindrical tube making jigs are immersed in the above-mentioned tube making solutions containing different concentrations of sodium chloride particles, so that the surface of the tube making jig is completely adhered to a layer of the tube making solution. The jigs are then taken out of the tube making solution and allowed to stand. Multiple nerve repair catheters can be made.

[0289] While standing still, the tetrahydrofuran solvent in the tube-making solution attached to the surface of the tube-making jig evaporates continuously, and the initial product of the nerve repair catheter gradually takes shape.

[0290] (3) Demolding, solvent removal, drying, and post-treatment steps: the same as in Example 1.

[0291] The performance test of the nerve repair catheter in this embodiment is carried out in the same manner as in Example 1.

[0292] The test results are shown in the following table:

[0293] Table: Comparative experiment of different porogen concentrations

[0294]

[0295] It can be seen from the above table that, when other conditions are the same: the greater the concentration of the porogen, the higher the porosity, the better the softness, and the worse the mechanical properties.

[0296] Example 7 illustrates the influence of the particle size of the porogen in each layer of the nerve repair conduit on the performance of the nerve repair conduit.

[0297] A method for preparing a single-layer nerve repair catheter using polyurethane biodegradable material comprises the following steps:

[0298] (1) Preparation of pipe-making solution: The polyurethane biodegradable biomaterial was dissolved in the tetrahydrofuran solvent shown in the following table to prepare 100 mL of polyurethane solution with a concentration of 35% (w / v).

[0299] Then add ground and sieved sodium chloride particles with a concentration of 250% (w / v), and control the particle size to be 1-10 μm, 10-50 μm, 50-100 μm, 100-200 μm, and stir until the sodium chloride particles are evenly distributed. Then, a variety of tube-making solutions can be prepared to make multiple nerve repair catheters.

[0300] (2) Tube making: The cylindrical tube making jig is immersed in the above-mentioned tube making solution containing different sodium chloride particle sizes, so that the surface of the tube making jig is completely adhered to a layer of tube making solution. Then, the jig is taken out from the tube making solution and allowed to stand. Under the condition of different sodium chloride particle sizes, multiple nerve repair catheters are made.

[0301] While standing still, the tetrahydrofuran solvent in the tube-making solution attached to the surface of the tube-making jig evaporates continuously, and the initial product of the nerve repair catheter gradually takes shape.

[0302] (3) Demolding, solvent removal, drying, and post-treatment steps: the same as in Example 1.

[0303] The performance test of the nerve repair catheter in this embodiment is carried out in the same manner as in Example 1.

[0304] The test results are shown in the following table:

[0305] Table: Comparative experiment of different porogen particle sizes

[0306]

[0307] Example 8 illustrates the influence of the thickness of the nerve repair catheter on the performance of the nerve repair catheter.

[0308] A method for preparing a single-layer nerve repair catheter using polyurethane biodegradable material comprises the following steps:

[0309] (1) Preparation of pipe making solution: The polyurethane biodegradable biomaterial was dissolved in each tetrahydrofuran solvent shown in the following table to prepare a biodegradable biomaterial solution with a concentration of 35% (w / v).

[0310] Then, add ground and sieved sodium chloride particles with a concentration of 250% (w / v), the particle size of which is controlled to be 10-20 μm, and stir until the sodium chloride particles are evenly distributed to obtain a pipe-making solution.

[0311] (2) Tube making: Immerse the cylindrical tube making jigs in the above-mentioned tube making solution, so that the surface of the tube making jig is completely covered with a layer of tube making solution, then take out the jigs and let them stand for 10 minutes. Repeat the above operation several times to make multiple nerve repair catheters with different thicknesses.

[0312] While standing still, the tetrahydrofuran solvent in the tube-making solution attached to the surface of the tube-making jig evaporates continuously, and the initial product of the nerve repair catheter gradually takes shape.

[0313] (3) Demolding, solvent removal, drying, and post-treatment steps: the same as in Example 1.

[0314] The performance test of the nerve repair catheter in this embodiment is carried out in the same manner as in Example 1.

[0315] The test results are shown in the following table:

[0316] Table: Comparative experiment of different thicknesses

[0317]

[0318] Example 9 illustrates the effect of multi-layer structure on promoting rapid nerve growth through nerve repair catheters with different structures of the present application:

[0319] 9-1 Single-layer tube structure, no holes:

[0320] (1) Preparation of pipe making solution: The polyurethane biodegradable biomaterial is dissolved in tetrahydrofuran solvent to prepare a biodegradable biomaterial solution with a concentration of 35% (w / v).

[0321] (2) Pipe making: Immerse a cylindrical pipe making jig in the above-mentioned pipe making solution until a layer of pipe making solution is completely attached to the surface of the pipe making jig. Then, take out the jig and let it stand for 10 minutes.

[0322] While standing still, the tetrahydrofuran solvent in the tube-making solution attached to the surface of the tube-making jig evaporates continuously, and the initial product of the nerve repair catheter gradually takes shape.

[0323] (3) Demolding, solvent removal, drying, and post-treatment steps: the same as in Example 1.

[0324] 9-2 Single-layer tube structure, with holes:

[0325] (1) Preparation of pipe making solution: The polyurethane biodegradable biomaterial is dissolved in tetrahydrofuran solvent to prepare a biodegradable biomaterial solution with a concentration of 35% (w / v).

[0326] Then, add ground and sieved sodium chloride particles with a concentration of 250% (w / v), the particle size of which is controlled to be 20 μm, and stir until the sodium chloride particles are evenly distributed to obtain a pipe-making solution.

[0327] (2) Pipe making: Immerse a cylindrical pipe making jig in the above-mentioned pipe making solution until a layer of pipe making solution is completely attached to the surface of the pipe making jig. Then, take out the jig and let it stand for 10 minutes.

[0328] While standing still, the tetrahydrofuran solvent in the tube-making solution attached to the surface of the tube-making jig evaporates continuously, and the initial product of the nerve repair catheter gradually takes shape.

[0329] (3) Demolding, solvent removal, drying, and post-treatment steps: the same as in Example 1.

[0330] 9-3 Double-layer tube structure, with small holes in the outer layer and holes in the inner layer (larger than the outer layer, but not too large to prevent the adhesion of nerve cells);

[0331] (1) Dissolving the polyurethane material: The polyurethane material was dissolved in tetrahydrofuran (THF) solvent to prepare 100 ml of polyurethane solutions with concentrations of 35% (w / v) and 35% (w / v).

[0332] (2) Preparation of Solution 1: Grind sodium chloride and sieve out sodium chloride with a particle size of 100 μm using a sieve. The sodium chloride concentration is 250% (w / v). Add it to the prepared 35% polyurethane material solution and stir it with a magnetic force until the sodium chloride is evenly dispersed in the solution to prepare Solution 1.

[0333] (3) Preparation of Solution 2: Grind sodium chloride and sieve out sodium chloride with a particle size of 15 μm using a sieve. The sodium chloride concentration is 250% (w / v). Add it to the prepared 35% biodegradable biomaterial solution and stir with a magnetic force until the sodium chloride is evenly dispersed in the solution to prepare Solution 2.

[0334] (4) Making a large-pore inner tube: insert a cylindrical tube-making jig vertically into the solution 1 and let it stand for 5 seconds so that a layer of the tube-making solution 1 adheres to the surface of the tube-making jig. Take out the tube-making jig and let it stand for 10 minutes.

[0335] (5) Preparation of microporous outer tube: After standing for 10 minutes in the above step, vertically insert the mold into solution 2 and stand for 5 seconds, so that the surface of the tube making jig is completely covered with a layer of tube making solution 2. Take out the mold and stand for 10 minutes.

[0336] While standing still, the tetrahydrofuran solvent in the tube-making solution attached to the surface of the tube-making jig evaporates continuously, and the initial product of the nerve repair catheter gradually takes shape.

[0337] (6) Demolding, solvent removal, drying, and post-treatment steps: the same as in Example 1.

[0338] 9-4 Three-layer tube structure, the outer layer has small holes, and the middle and inner layers have holes:

[0339] (1) Dissolving the polyurethane material: Dissolve the polyurethane material in tetrahydrofuran (THF) to prepare 100 ml of each of the polyurethane material solutions with concentrations of 35% (w / v), 35% (w / v), and 35% (w / v).

[0340] (2) Preparation of Solution 1: Grind sodium chloride and sieve out sodium chloride with a particle size of 100 μm using a sieve. The sodium chloride concentration is 250% (w / v). Add it to the prepared polyurethane solution with a concentration of 35%, and stir with a magnetic force until the sodium chloride is evenly dispersed in the solution to prepare Solution 1.

[0341] (3) Preparation of Solution 2: Grind sodium chloride and sieve out sodium chloride with a particle size of 250 μm using a sieve. The sodium chloride concentration is 250% (w / v). Add the sodium chloride to the prepared polyurethane solution with a concentration of 35%, and stir with a magnetic force until the sodium chloride is evenly dispersed in the solution to prepare Solution 2.

[0342] (4) Preparation of Solution 3: Grind sodium chloride and sieve out sodium chloride with a particle size of 15 μm. The sodium chloride concentration is 250% (w / v). Add it to the prepared polyurethane solution with a concentration of 35%, and stir with a magnetic force until the sodium chloride is evenly dispersed in the solution to prepare Solution 3.

[0343] (5) Making a middle-hole inner tube: insert a cylindrical tube-making jig vertically into the solution 1 and let it stand for 5 seconds so that a layer of the tube-making solution 1 adheres to the surface of the tube-making jig. Take out the tube-making jig and let it stand for 10 minutes.

[0344] (6) Making a large-pore transition layer tube: After the tube making jig has been left to stand for 10 minutes in the previous step, vertically insert it into Solution 2 and let it stand for 5 seconds, so that Solution 2 completely covers the surface of the mold. Take out the mold and let it stand for 10 minutes.

[0345] (7) Preparation of microporous outer tube: After the tube preparation jig has been left to stand for 10 minutes in the previous step, vertically insert it into solution 3 and let it stand for 5 seconds, so that the surface of the jig is completely covered by solution 3. Take out the jig and let it stand for 10 minutes.

[0346] While standing still, the tetrahydrofuran solvent in the tube-making solution attached to the surface of the tube-making jig evaporates continuously, and the initial product of the nerve repair catheter gradually takes shape.

[0347] (8) Demolding, solvent removal, drying, and post-treatment steps: the same as in Example 1.

[0348] 9-5 is a multi-layer tube structure, with an outer layer, a middle layer (same as 9-4), and an inner layer structure with multiple layers arranged in parallel.

[0349] The method for preparing the multi-bundle small tube structure nerve repair catheter comprises the following steps:

[0350] A solution for preparing inner layer multi-bundle nerve repair catheters is prepared, multiple inner layer tubes are prepared by a casting method, the multiple inner layer tubes are curled into bundles, and the bundles are inserted into the middle layer tubes to obtain the nerve repair catheters.

[0351] In order to demonstrate the effects of the nerve repair conduits with different structures in the present application on promoting the rapid growth of nerves, the nerve repair conduits prepared by the above 9-1, 9-2, 9-3, 9-4, and 9-5 are now subjected to effect tests, as follows:

[0352] In the same formula, the thicker the tube wall, the better the mechanical properties; in the case of the same thickness, the mechanical properties of the salt-free nerve repair catheter are the best; the less salt content, the smaller the porosity, the smaller the particle size, the better the mechanical properties; the more salt content, the higher the porosity, the larger the particle size, the worse the mechanical properties. The thicker the layer with less salt content and smaller salt particles, the better the mechanical properties and the lower the porosity.

[0353] Example 10 illustrates the effect of promoting rapid nerve growth by setting a growth guiding structure on the nerve repair catheter.

[0354] 10-1: Based on the nerve repair catheter prepared in the above Example 9-1, longitudinal grooves are set on the inner surface of the inner layer of the above nerve repair catheter to play a role in growth guidance.

[0355] 10-2: Based on the nerve repair catheter prepared in the above Example 9-2, longitudinal grooves are set on the inner surface of the inner layer of the above nerve repair catheter to play a role in growth guidance.

[0356] 10-3: Based on the nerve repair catheter prepared in the above Example 9-3, longitudinal grooves are set on the inner surface of the inner layer of the above nerve repair catheter to play a role in growth guidance.

[0357] 10-4: Based on the nerve repair catheter prepared in the above Example 9-4, longitudinal grooves are set on the inner surface of the inner layer of the above nerve repair catheter to play a role in growth guidance.

[0358] 10-5: Based on the nerve repair catheter prepared in the above embodiment 9-5, longitudinal grooves are provided on the inner surface of the inner layer of the above nerve repair catheter to play a role in growth guidance.

[0359] The nerve repair conduits prepared by the above 10-1, 10-2, 10-3, 10-4, 10-5 and the nerve repair conduits prepared by the above 9-1, 9-2, 9-3, 9-4, 9-5 were subjected to effect tests, as follows:

[0360] Compared with the nerve repair catheter prepared in Example 9, in this embodiment, a longitudinal groove structure is provided on the inner surface of the nerve repair catheter, and nerve cells grow along the extension direction of the groove structure.

[0361] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, rather than to limit it. Although the present invention has been described in detail with reference to the aforementioned embodiments, those skilled in the art should understand that they can still modify the technical solutions described in the aforementioned embodiments, or replace some or all of the technical features therein with equivalents. However, these modifications or replacements do not cause the essence of the corresponding technical solutions to deviate from the scope of the technical solutions of the embodiments of the present invention.

Claims

1. A nerve repair catheter, characterized in that: The nerve repair catheter is mainly made of biodegradable materials, wherein: the outer surface of the nerve repair catheter has a grooved structure; And / or, the inner surface of the nerve repair conduit has a growth guiding structure, and the growth guiding structure is a longitudinal groove provided on the inner surface of the inner layer of the nerve repair conduit; The nerve repair catheter is a multi-layer structure nerve repair catheter, and the multi-layer structure nerve repair catheter includes a double-layer structure nerve repair catheter or a three-layer structure nerve repair catheter; The inner diameter of the inner layer of the double-layer structure nerve repair catheter is 0.8-15 mm, the thickness of the inner layer is 0.08-1.5 mm, and the pore size of the inner layer is 30-200 μm; the inner diameter of the outer layer is 1.1-16.5 mm, the thickness of the outer layer is 0.1-1.5 mm, and the pore size of the outer layer is 0-30 μm; The inner diameter of the inner layer of the three-layer structure nerve repair catheter is 0.8-14.5 mm, the thickness of the inner layer is 0.06-1.5 mm, and the pore size of the inner layer is 30-200 μm; the inner diameter of the middle layer is 1.0-16 mm, the thickness of the middle layer is 0.08-1.5 mm, and the pore size of the middle layer is 50-300 μm; the inner diameter of the outer layer is 1.1-16 mm, the thickness of the outer layer is 0.06-1.5 mm, and the pore size of the outer layer is 0-30 μm; The method for preparing the multi-layer structure nerve repair catheter comprises the following steps: (a) dissolving a biodegradable material in a non-alcoholic polar solvent to obtain a solution A; then adding a porogen and stirring until the porogen is evenly distributed to obtain a pipe-making solution; The concentration range of the porogen in the pipe making solution is 0-500w / v; (b) immersing a cylindrical tube-making jig into the tube-making solution, so that a layer of the tube-making solution adheres to the surface of the tube-making jig, and then taking it out and letting it stand; then demolding and removing the solvent, and drying to obtain a nerve repair catheter; Repeat step (b) once to obtain a double-layer structure nerve repair catheter; or repeat step (b) twice to obtain a three-layer structure nerve repair catheter.

2. The nerve repair catheter according to claim 1, characterized in that: The inner layer of the multi-layered nerve repair catheter is a plurality of bundles of small tubes arranged in parallel; The inner diameter of the multiple bundles of small tubes is 0.8-14.5 mm, the thickness is 0.01-0.8 mm, and the pore size is 30-200 um.

3. The nerve repair catheter according to claim 1, characterized in that: The biodegradable material includes at least one of polylactic acid, polycaprolactone, polyhydroxyalkanoate, polybutylene succinate, polybutylene terephthalate-adipate-butylene ester, polyvinyl alcohol and polycarbonate.

4. The nerve repair catheter according to claim 1, characterized in that: Both ends of the nerve repair catheter are provided with positioning structures or fixing structures.

5. The nerve repair catheter according to claim 4, characterized in that: The positioning structure includes at least one of a positioning hole, a positioning groove or a positioning protrusion; The fixing structure includes at least one of a flare, a spike or a barb.

6. The nerve repair catheter according to claim 1, characterized in that: The non-alcohol polar solvent includes at least one of tetrahydrofuran, ethylene dichloride, dimethyl ether or N,N-dimethylformamide.

7. The nerve repair catheter according to claim 1, characterized in that: The porogen includes at least one of sodium chloride, sucrose, gelatin balls, monosodium glutamate, modified cellulose, urea, polyethylene glycol, and polyvinyl pyrrolidone.

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