Medical repair material, preparation method and medical transplantation bag

Abstract

The invention relates to the technical field of biomedical treatment, in particular to a medical repair material, a preparation method and a medical transplantation bag. The method comprises the following steps: providing a piezoelectric elastomer and polylactic acid fibers; a solution obtained by mixing dichloromethane and N, N-dimethylformamide is used as a first solution; dichloromethane is used as a second solution; providing a first injector, dissolving a piezoelectric elastomer in a first solution, and adding the solution into the first injector; providing a second injector, adding the second solution into the second injector, and dissolving the piezoelectric elastomer in the second solution; the first injector and the second injector are subjected to electrostatic spinning treatment, so that the piezoelectric fiber film is discharged out of the output end of the first injector, and the fiber skeleton is discharged out of the output end of the second injector; and after the piezoelectric fiber film is attached to the fiber skeleton, sequentially carrying out drying treatment and annealing treatment to obtain the medical repair material. The problem that an existing piezoelectric material is high in modulus and can be well attached to an organ in the organ transplantation process is solved.

Description

[Technical field]

[0001] The present invention relates to the field of biomedical technology, and in particular to a medical repair material, a preparation method and a medical transplant bag. [Background technology]

[0002] Piezoelectric materials have been found to accelerate the healing of wounds, muscles and tendon defects through effective in situ electrical stimulation. Therefore, they are widely used in the medical field as biomedical materials.

[0003] In the prior art, when transplanting an organ, it is usually necessary to apply electrical stimulation to the nerve tissue in the organ to promote the recovery of organ function. Piezoelectric materials can be made into monitors, which can not only continuously monitor the physiological parameters of the organ during organ transplantation, but also help doctors monitor the status of the transplanted organ in real time. In addition, the monitor can also release electrical signals to stimulate the nerves of the organ to promote the recovery of organ function.

[0004] However, the elastic modulus of the piezoelectric material in the prior art is relatively high, which means that the monitor can only monitor and provide electrical signals during the organ transplantation process, and cannot be better attached to the organ to help the organ transplantation. Therefore, it is particularly important to find a material that can not only attach to the organ to help the organ transplantation, but also monitor and repair the organ. [Summary of the invention]

[0005] In order to solve the problem that the existing piezoelectric material has a high modulus and forms a good adhesion with the organ during the organ transplantation process, the present invention provides a medical repair material, a preparation method and a medical transplantation bag.

[0006] In order to solve the above technical problems, the present invention provides the following technical solutions: a method for preparing a medical repair material, comprising the following steps:

[0007] Providing piezoelectric elastomers and polylactic acid fibers;

[0008] Providing a dichloromethane solution and an N,N-dimethylformamide solution, and using a solution obtained by mixing the dichloromethane and the N,N-dimethylformamide as a first solution;

[0009] providing a dichloromethane solution, using dichloromethane as a second solution;

[0010] The piezoelectric elastomer is dissolved in a first solution and subjected to an electrospinning process to form a piezoelectric fiber film, and the polylactic acid fiber is dissolved in a second solution and subjected to an electrospinning process to form a fiber skeleton;

[0011] The piezoelectric fiber film is attached to the fiber skeleton and then subjected to drying and annealing treatments in sequence to obtain the medical repair material.

[0012] Preferably, the elastic modulus of the medical repair material is 0.1-3Mpa.

[0013] Preferably, providing the piezoelectric elastomer comprises the following steps:

[0014] providing butanediol, lactic acid, sebacic acid and itaconic acid as raw materials;

[0015] The raw materials are mixed and reacted to obtain a preformed elastomer;

[0016] The prefabricated elastomer is dissolved by chlorinated hydrocarbon, and then precipitated and dried to obtain the piezoelectric elastomer.

[0017] Preferably, the molar ratio of hydroxyl groups to carboxyl groups in the preformed elastomer is (1.5-1):1, and the molar ratio of itaconic acid to carboxyl groups in the preformed elastomer is 1:(8-12).

[0018] Preferably, the mixing reaction of the raw materials specifically comprises:

[0019] The raw materials are mixed and reacted at a first temperature for a first time, and then the temperature is raised to a second temperature for a second time.

[0020] After reacting at the second temperature for a second time, the temperature is lowered to a third temperature, and after the temperature is lowered, a catalyst is added to react for a third time to obtain a prefabricated elastomer;

[0021] Among them, the second temperature>the first temperature>the third temperature.

[0022] Preferably, the piezoelectric elastomer is obtained after sequentially undergoing precipitation and drying processes, specifically comprising:

[0023] Adding excess cold methanol to the solution after the prefabricated elastomer is dissolved, the solution is allowed to stand and filtered in sequence to obtain a precipitated sample, and the precipitated sample is dried at 50-60° C. to obtain the piezoelectric elastomer.

[0024] Preferably, attaching the piezoelectric fiber film to the fiber skeleton specifically includes:

[0025] providing a first syringe, providing a second syringe and a collector;

[0026] Dissolving the piezoelectric elastomer in the first solution and then adding the solution into the first syringe;

[0027] Dissolving polylactic acid fiber in the second solution and adding the solution into the second syringe;

[0028] The first syringe and the second syringe simultaneously perform electrostatic spinning under the action of a voltage of 10 to 12 kV, and the discharged piezoelectric fiber film adheres to the surface of the discharged fiber skeleton in the collector;

[0029] The piezoelectric fiber film and the fiber skeleton are both mesh structures.

[0030] Preferably, the steps of sequentially performing drying and annealing to obtain the medical repair material include:

[0031] The fiber skeleton with the piezoelectric fiber film attached thereto is dried as a preform, and then annealed at 130° C. to 140° C. for 50 to 60 minutes. The annealed preform is cooled to room temperature to obtain a medical repair material.

[0032] In order to solve the above technical problems, the present invention provides another technical solution as follows: a medical repair material is prepared by the above-mentioned preparation method of the medical repair material.

[0033] In order to solve the above technical problems, the present invention provides another technical solution as follows: a medical transplant bag, comprising a main body and at least two connecting wires, the main body is provided with a signal input port and a signal output port, the connecting wires are used to connect the signal input port with an external monitoring device and to connect the signal output port with an external monitoring device, and the material of the main body is the above-mentioned medical repair material.

[0034] Compared with the prior art, the medical repair material, preparation method and medical transplant bag provided by the present invention have the following beneficial effects:

[0035] 1. A method for preparing a medical repair material provided in an embodiment of the present invention comprises the following steps:

[0036] Providing piezoelectric elastomers and polylactic acid fibers;

[0037] Providing a dichloromethane solution and an N,N-dimethylformamide solution, and using a solution obtained by mixing the dichloromethane and the N,N-dimethylformamide as a first solution;

[0038] providing a dichloromethane solution, using dichloromethane as a second solution;

[0039] The piezoelectric elastomer is dissolved in a first solution and subjected to an electrospinning process to form a piezoelectric fiber film, and the polylactic acid fiber is dissolved in a second solution and subjected to an electrospinning process to form a fiber skeleton;

[0040] The piezoelectric fiber film is attached to the fiber skeleton and then subjected to drying and annealing treatments in sequence to obtain the medical repair material.

[0041] The medical repair material can provide effective in-situ electricity to stimulate the surface of the organ to be transplanted, and the stimulated organ can repair itself. Furthermore, the piezoelectric fiber film provides the characteristic of low elastic modulus, so that the medical repair material can be well attached to the surface of the organ to be transplanted. And the medical repair material prepared in this embodiment also has a monitoring function, and only needs to be connected to the external monitoring equipment by telecommunication. When the medical repair material is attached to the surface of the organ to be transplanted, it can continuously receive the physiological status information of the organ in the process of generating piezoelectric signals, and transmit the physiological status information to the external monitoring equipment.

[0042] 2. The elastic modulus of the medical repair material in the embodiment of the present invention is 0.1-3Mpa. The elastic modulus of the medical repair material in this embodiment is lower than that of the existing piezoelectric material, so that it has better flexibility and better tensile properties, and can be more easily attached to the surface of the organ to be transplanted. In addition, the piezoelectric elastomer prepared from the above material and the medical repair material prepared together with the provided polylactic acid fiber have good biodegradability and biocompatibility.

[0043] 3. Providing a piezoelectric elastic body in an embodiment of the present invention comprises the following steps:

[0044] providing butanediol, lactic acid, sebacic acid and itaconic acid as raw materials;

[0045] The raw materials are mixed and reacted to obtain a preformed elastomer;

[0046] The prefabricated elastomer is dissolved by chlorinated hydrocarbon, and then precipitated and dried to obtain the piezoelectric elastomer.

[0047] The participation of lactic acid and itaconic acid in the copolymerization reaction makes the piezoelectric effect of the piezoelectric elastomer even stronger. Sebacic acid and butanediol in this example can provide a long straight carbon chain, that is, a long flexible chain segment, which helps to lower the glass transition temperature of the product to reduce the elastic modulus of the piezoelectric elastomer. The C=C double bond in itaconic acid can provide a curing cross-linking site for the piezoelectric elastomer during the copolymerization process. During the later heat treatment, the curing cross-linking sites can make the piezoelectric elastomer have a network structure, and the network structure further reduces the modulus of the piezoelectric elastomer.

[0048] 4. The molar ratio of hydroxyl and carboxyl in the prefabricated elastomer in the embodiment of the present invention is (1.5-1):1, and the molar ratio of itaconic acid and carboxyl in the prefabricated elastomer is 1:(8-12). This embodiment selectively sets the molar ratio of hydroxyl and carboxyl, and the molar ratio of itaconic acid and carboxyl, so that the prepared piezoelectric elastomer has not only a lower elastic modulus, but also better piezoelectric properties. This solves the problem in the prior art that flexible materials and piezoelectric materials are mixed, resulting in the piezoelectric material not being able to have both piezoelectric properties and flexibility.

[0049] 5. In the embodiment of the present invention, the raw materials are mixed and reacted, specifically comprising:

[0050] The raw materials are mixed and reacted at a first temperature for a first time, and then the temperature is raised to a second temperature for a second time.

[0051] After reacting at the second temperature for a second time, the temperature is lowered to a third temperature, and after the temperature is lowered, a catalyst is added to react for a third time to obtain a prefabricated elastomer;

[0052] The second temperature is greater than the first temperature and greater than the third temperature. The prefabricated elastomer with a lower modulus is obtained by selectively controlling the temperature.

[0053] 6. The piezoelectric elastomer obtained by sequentially performing precipitation and drying treatments in the embodiment of the present invention specifically comprises:

[0054] Excessive cold methanol is added to the solution after the prefabricated elastomer is dissolved, and then the solution is allowed to stand and filtered in sequence to obtain a precipitated sample. The precipitated sample is dried at 50-60° C. to obtain the piezoelectric elastomer. The operation is simple.

[0055] 7. In the embodiment of the present invention, attaching the piezoelectric fiber film to the fiber skeleton specifically includes:

[0056] providing a first syringe, providing a second syringe and a collector;

[0057] Dissolving the piezoelectric elastomer in the first solution and then adding the solution into the first syringe;

[0058] Dissolving polylactic acid fiber in the second solution and adding the solution into the second syringe;

[0059] The first syringe and the second syringe simultaneously perform electrostatic spinning under the action of a voltage of 10 to 12 kV, and the discharged piezoelectric fiber film adheres to the surface of the discharged fiber skeleton in the collector;

[0060] The piezoelectric fiber film and the fiber skeleton are both mesh structures.

[0061] The polylactic acid fiber is a skeleton structure, which can provide a certain support strength. The piezoelectric fiber film provides piezoelectric properties and low elastic modulus. The final medical repair material has good bending and stretching properties, which can solve the problems of insufficient flexibility and poor adhesion to the kidney of existing implants.

[0062] 8. In the embodiment of the present invention, the drying treatment and the annealing treatment are sequentially performed to obtain the medical repair material, which comprises:

[0063] The fiber skeleton with the piezoelectric fiber film attached is dried as a preform, and then annealed at 130°C to 140°C for 50 to 60 minutes, and the annealed preform is cooled to room temperature to obtain a medical repair material. The obtained medical repair material is simple and convenient to operate, and the formed medical repair material has good bending and stretching properties.

[0064] 9. The embodiment of the present invention also provides a medical repair material, which has the same beneficial effects as the preparation method of the above-mentioned medical repair material, and will not be described in detail here.

[0065] 10. The embodiment of the present invention also provides a medical transplant bag, which has the same beneficial effects as the preparation method of the above-mentioned medical repair material, and will not be described in detail here.

Brief Description of the Drawings

[0066] Figure 1 It is a schematic flow chart of a method for preparing a medical repair material provided in the first embodiment of the present invention.

[0067] Figure 2 It is a schematic structural diagram of a piezoelectric fiber film and a fiber skeleton of a medical repair material provided by the first embodiment of the present invention.

[0068] Figure 3a It is a schematic diagram showing the effect of the mass ratio of the co-spun yarn of polylactic acid fiber and piezoelectric elastomer on the piezoelectric properties of the finally formed medical repair material in the present invention.

[0069] Figure 3b It is a schematic diagram of the therapeutic effect of the medical repair material provided by the present invention when applied in the field of kidney transplantation.

[0070] Figure 4a This is a schematic diagram of the therapeutic effect of the medical repair material provided by the present invention in the field of ureteral repair. Figure 1 .

[0071] Figure 4b This is a schematic diagram of the therapeutic effect of the medical repair material provided by the present invention in the field of ureteral repair. Figure 2 .

[0072] Figure 4c This is schematic diagram three of the therapeutic effect of the medical repair material provided by the present invention when applied in the field of ureteral repair.

[0073] Figure 5 It is a schematic structural diagram of a medical transplant bag provided by the third embodiment of the present invention.

[0074] Description of the accompanying drawings:

[0075] 1. Medical transplant bags;

[0076] 11. Main body; 12. Connection line; 13. Signal input port; 14. Signal output port. [Specific implementation method]

[0077] In order to make the purpose, technical solution and advantages of the present invention more clearly understood, the present invention is further described in detail below in conjunction with the accompanying drawings and implementation examples. It should be understood that the specific embodiments described herein are only used to explain the present invention and are not intended to limit the present invention.

[0078] In the embodiments provided by the present invention, it should be understood that "B corresponding to A" means that B is associated with A, and B can be determined according to A. However, it should also be understood that determining B according to A does not mean determining B only according to A, and B can also be determined according to A and / or other information.

[0079] It should be understood that the "one embodiment" or "an embodiment" mentioned throughout the specification means that the specific features, structures or characteristics related to the embodiment are included in at least one embodiment of the present invention. Therefore, "in one embodiment" or "in an embodiment" appearing throughout the specification does not necessarily refer to the same embodiment. In addition, these specific features, structures or characteristics can be combined in one or more embodiments in any suitable manner. Those skilled in the art should also be aware that the embodiments described in the specification are all optional embodiments, and the actions and modules involved are not necessarily required for the present invention.

[0080] In various embodiments of the present invention, it should be understood that the size of the serial numbers of the above-mentioned processes does not mean the necessary order of execution. The execution order of each process should be determined by its function and internal logic, and should not constitute any limitation on the implementation process of the embodiments of the present invention.

[0081] The flow chart and block diagram in the accompanying drawings of the present invention illustrate the possible architecture, function and operation of the system, method and computer program product according to various embodiments of the present application. In this regard, each box in the flow chart or block diagram can represent a module, a program segment or a part of a code, and the module, the program segment or a part of the code contains one or more executable instructions for realizing the specified logical function. It should also be noted that in some alternative implementations, the functions marked in the box can also occur in a sequence different from that marked in the accompanying drawings. For example, two boxes represented in succession can actually be executed substantially in parallel, and they can sometimes be executed in the opposite order, which is determined based on the functions involved. It should be particularly noted that each box in the block diagram and / or flow chart, and the combination of the boxes in the block diagram and / or flow chart can be implemented by a dedicated hardware-based system that performs a specified function or operation, or can be implemented by a combination of dedicated hardware and computer instructions.

[0082] Piezoelectric materials have been found to accelerate the healing of wounds, muscles and tendon defects through effective in situ electrical stimulation. Therefore, they are widely used in the medical field as biomedical materials.

[0083] In the prior art, when transplanting an organ, it is usually necessary to apply electrical stimulation to the nerve tissue in the organ to promote the recovery of organ function. Piezoelectric materials can be made into monitors, which can not only continuously monitor the physiological parameters of the organ during organ transplantation, but also help doctors monitor the status of the transplanted organ in real time. In addition, the monitor can also release electrical signals to stimulate the nerves of the organ to promote the recovery of organ function.

[0084] The elastic modulus of the piezoelectric material in the prior art is relatively high, which means that the monitor can only monitor and provide electrical signals during the organ transplantation process, and cannot be better attached to the organ to help the organ transplantation. Therefore, it is particularly important to find a material that can not only attach to the organ to help the organ transplantation, but also monitor and repair the organ.

[0085] See also Figure 1 The first embodiment of the present invention provides a method for preparing a medical repair material, comprising the following steps:

[0086] S1, providing a piezoelectric elastomer and polylactic acid fiber;

[0087] S2, providing a dichloromethane solution and an N, N-dimethylformamide solution, and using a solution obtained by mixing the dichloromethane and the N, N-dimethylformamide as a first solution;

[0088] S3, providing a dichloromethane solution, using dichloromethane as the second solution;

[0089] S4, dissolving the piezoelectric elastomer in the first solution and performing an electrospinning process to form a piezoelectric fiber film, and dissolving the polylactic acid fiber in the second solution and performing an electrospinning process to form a fiber skeleton;

[0090] S5, attaching the piezoelectric fiber film to the fiber skeleton and then performing drying and annealing treatments in sequence to obtain a medical repair material.

[0091] Understandably, traditional medical monitors are usually in the form of thin films. First, during organ transplantation, the surface of human organs is not flat, and it is difficult for the monitor to be easily attached to the surface of the organ. In addition, the elastic modulus of the existing monitors made of piezoelectric materials is low, that is, the monitor itself has a certain strength. If the monitor is forcibly attached to the surface of the organ, it will also cause damage to the organ to be transplanted. Therefore, it is particularly important to seek a medical repair material that has a low elastic modulus so that it can fit well with human organs in the biomedical field, such as the surface of the skin, wound surface, muscle, defective tendon, ureter, urethra, bladder or the surface of the organ to be transplanted.

[0092] In this embodiment, a piezoelectric elastomer and polylactic acid fiber are first provided. It should be understood that the piezoelectric elastomer itself has a low elastic modulus, so that the medical repair material prepared using this raw material also has a low elastic modulus, so that it has good bending and stretching properties when used in the biomedical field, and can solve the problem of insufficient flexibility of existing implants or monitors and poor adhesion to the organ to be transplanted. Among them, the polylactic acid fiber is a skeleton structure, which can provide a certain support strength.

[0093] Specifically, in this embodiment, a dichloromethane solution and an N, N-dimethylformamide solution are provided, a solution mixed with dichloromethane and N, N-dimethylformamide is used as the first solution, and the piezoelectric elastomer is dissolved in the first solution for electrostatic spinning to form a piezoelectric fiber film. It should be understood that the piezoelectric fiber film formed by electrostatic spinning has a mesh structure. Further, a dichloromethane solution is provided, and dichloromethane is used as the second solution; polylactic acid fiber is dissolved in the second solution for electrostatic spinning to form a fiber skeleton. The fiber skeleton formed by electrostatic spinning has a mesh structure. Further, the piezoelectric fiber film with a mesh structure is attached to the fiber skeleton with a mesh structure and dried and annealed in sequence to obtain a medical repair material. Among them, the piezoelectric fiber film can achieve effective coverage of the polylactic acid fiber skeleton, and provide nodes at the junction of the fiber skeleton to convert weak mechanical vibrations into global vibrations of the fiber film. In addition, the piezoelectric fiber film has piezoelectric properties, so during the vibration process, the medical repair material prepared by the piezoelectric fiber film can provide effective in-situ electricity to stimulate the surface of the organ to be transplanted, and the stimulated organ can repair itself. Furthermore, the piezoelectric fiber film provides the characteristic of low elastic modulus, so that the medical repair material can be well attached to the surface of the organ to be transplanted. And the medical repair material prepared in this embodiment also has a monitoring function, and only needs to be connected to the external monitoring equipment by telecommunication. When the medical repair material is attached to the surface of the organ to be transplanted, it can continuously receive the physiological status information of the organ in the process of generating piezoelectric signals, and transmit the physiological status information to the external monitoring equipment.

[0094] For example, renal ischemia-reperfusion injury is an inevitable kidney damage process during kidney transplantation, which seriously damages the quality of transplanted kidneys and causes clinical adverse reactions such as delayed recovery of transplanted kidney function and rejection reactions. However, there is currently no clear effective treatment for renal ischemia-reperfusion in clinical practice. Specifically, the medical repair material prepared by the method provided in this embodiment can be applied to the field of kidney transplantation. The piezoelectric fiber film in the medical repair material can achieve effective coverage of the polylactic acid fiber skeleton, and provide nodes at the junction of the fiber skeleton to convert weak mechanical vibrations into global vibrations of the fiber film, which can provide weak electrical stimulation locally and in situ in the kidney in real time, and promote the repair of renal tubules in renal ischemia-reperfusion injury; on the other hand, the medical repair material has good bending and stretching properties, which can solve the problems of insufficient flexibility of existing implants and poor adhesion to the kidney.

[0095] Specifically, the elastic modulus of the medical repair material is 0.1-3Mpa. It can be understood that the elastic modulus of the medical repair material in this embodiment is lower than that of the existing piezoelectric material, so that it has better flexibility and better tensile properties, and can be more easily applied to the surface of the organ to be transplanted. In addition, the piezoelectric elastomer prepared from the above materials and the medical repair material prepared together with the provided polylactic acid fiber have good biodegradability and biocompatibility. When it is coated on the outer surface of the organ, it has no harmful stimulation to the organ, or when it is used for the repair of wounds, muscles, and defective tendons, it has no harmful stimulation to the receptor after implantation, and can be completely degraded within a certain period of time without the need for removal.

[0096] Further, providing the piezoelectric elastomer comprises the following steps:

[0097] S11, providing butanediol, lactic acid, sebacic acid and itaconic acid as raw materials;

[0098] S12, mixing and reacting the raw materials to obtain a prefabricated elastomer;

[0099] S13, dissolving the prefabricated elastomer with chlorinated hydrocarbons, and then sequentially performing precipitation and drying processes to obtain a piezoelectric elastomer.

[0100] It can be understood that the raw materials of the piezoelectric elastomer in this embodiment are prepared by copolymerization of butanediol (BDO), lactic acid (LA), sebacic acid (SA) and itaconic acid (IA). Lactic acid and itaconic acid can provide C=O double bonds to enhance the piezoelectric properties of the piezoelectric elastomer. In addition, the participation of lactic acid and itaconic acid in the copolymerization reaction makes the piezoelectric effect of the piezoelectric elastomer even greater. If lactic acid is directly used for polymerization to form polylactic acid, although it has good piezoelectric properties, its modulus is high, and the final product prepared cannot be well applied to the surface of organ transplantation. Sebacic acid and butanediol in this example can provide long straight carbon chains, that is, provide a long flexible chain segment, which helps to reduce the glass transition temperature of the product to reduce the elastic modulus of the piezoelectric elastomer, so that the piezoelectric elastomer can have a good deformation ability, so that when the piezoelectric elastomer is subjected to external forces, the piezoelectric elastomer can deform in response to the forces. Among them, the C=C double bonds in itaconic acid can provide curing crosslinking sites for the piezoelectric elastomer during the copolymerization process. In the later stage of electrospinning, the solidified cross-linking sites can make the piezoelectric fiber film present a network structure, and the network structure further reduces the modulus of the piezoelectric fiber film.

[0101] Therefore, the piezoelectric elastomer prepared from the raw material has a lower elastic modulus, and the medical repair material prepared from the piezoelectric elastomer is easier to adhere to the surface of the organ to be transplanted.

[0102] Specifically, the molar ratio of hydroxyl groups to carboxyl groups in the preformed elastomer is (1.5-1):1, and the molar ratio of itaconic acid to carboxyl groups in the preformed elastomer is 1:(8-12).

[0103] Preferably, the molar ratio of hydroxyl to carboxyl in the prefabricated elastomer is 1.1:1. The hydroxyl groups are mainly provided by alcohols, such as hydroxyl groups on butanediol and lactic acid. The carboxyl groups are mainly provided by acids, such as lactic acid, sebacic acid and itaconic acid. Since the boiling point of alcohols is slightly lower than that of acids, alcohols are more likely to produce vaporized products when reacting at high temperatures, resulting in an imbalance in the ratio of alcohol and acid in the reaction. Therefore, in this embodiment, a higher proportion of alcohol is selectively designed, which is beneficial to avoid the imbalance of alcohol and acid in the process of preparing piezoelectric elastomers.

[0104] Preferably, the molar ratio of itaconic acid to carboxyl in the prefabricated elastomer is 1:10. Because the C=C double bond in itaconic acid can provide a curing crosslinking site for the piezoelectric elastomer during the copolymerization process. The curing crosslinking site helps to make the piezoelectric fiber film present a mesh structure, so that the modulus of the piezoelectric fiber film is further reduced. If the amount of itaconic acid is too low, the C=C double bond provided by itaconic acid cannot provide sufficient curing crosslinking sites, resulting in the inability to form a mesh structure. If the amount of itaconic acid is too high, thermal oxidation occurs under high temperature reaction, causing itaconic acid to crosslink in advance. That is, the piezoelectric elastomer formed by it has been crosslinked before the electrospinning process, and the piezoelectric fiber film with a mesh structure cannot be formed during the electrospinning process, resulting in the inability to be made into a medical repair material.

[0105] It should be understood that in order to obtain lower flexibility, traditional piezoelectric materials usually use flexible materials and piezoelectric materials for mixing. However, the flexible material itself does not have piezoelectric properties, so if the two materials are directly mixed, the piezoelectric properties of the piezoelectric material will be reduced. Therefore, the traditional mixing method has the problem that both piezoelectric properties and flexibility cannot be achieved at the same time. In this embodiment, by selectively selecting the reaction monomer, lactic acid and itaconic acid can provide C=O double bonds to enhance the piezoelectric properties of the piezoelectric elastomer. Sebacic acid and butanediol can be used to provide long straight carbon chains to reduce the elastic modulus, and the C=C double bonds in itaconic acid can be used to provide curing crosslinking sites for the piezoelectric elastomer during the copolymerization process. The final piezoelectric fiber film has a mesh structure and reduces the elastic modulus. Finally, in the process of preparing medical repair materials, the piezoelectric elastomer is selected to be electrostatically spun into a piezoelectric fiber film with a mesh structure. Compared with the traditional dense film. After electrospinning, it will be fibrous, and the piezoelectric fiber film formed into a mesh structure after cross-linking has a lower elastic modulus and better adhesion. Therefore, the medical repair material prepared in this embodiment can be better attached to the organ to be transplanted.

[0106] It should be noted that, in this embodiment, by selectively setting the molar ratio of hydroxyl group to carboxyl group, and the molar ratio of itaconic acid to carboxyl group, the prepared piezoelectric elastomer has not only a lower elastic modulus, but also better piezoelectric properties. This solves the problem in the prior art that the piezoelectric material cannot have both piezoelectric properties and flexibility due to mixing flexible materials and piezoelectric materials.

[0107] Specifically, the mixing reaction of the raw materials specifically includes:

[0108] S121, mixing the raw materials, reacting them at a first temperature for a first time, and then heating them to a second temperature for a second time.

[0109] S122, reacting at the second temperature for a second time, then cooling to a third temperature, and after the cooling is completed, adding a catalyst and reacting for a third time to obtain a prefabricated elastomer;

[0110] Among them, the second temperature>the first temperature>the third temperature.

[0111] It should be understood that in the process of preparing piezoelectric elastomers by copolymerization of raw materials butanediol, lactic acid, sebacic acid and itaconic acid, the control of reaction conditions is extremely important. Specifically, after the raw materials are mixed under a nitrogen atmosphere, the mixture can be heated to a second temperature for a second time after reacting at a first temperature for a first time. The first temperature is 125°C to 130°C, and the first time is 40min to 1h. After the temperature treatment, the second temperature is 175°C to 180°C, and the second time is 1.8min to 2h. It should be understood that after the raw materials are mixed, the monomers in the raw materials themselves will undergo homopolymerization, resulting in poor copolymerization. After the temperature treatment, the temperature increase can cause the monomers that undergo homopolymerization to decompose back to the monomer state, preventing the homopolymerization from proceeding, thereby avoiding the occurrence of homopolymerization. Further, after reacting at the second temperature for a second time, the temperature is lowered to a third temperature, and after the temperature reduction is completed, a catalyst is added to react for a third time to obtain a prefabricated elastomer. Among them, the third temperature is 100°C to 105°C. The third time is 7.5 to 8h. Cooling can adapt the reaction temperature of the catalyst to accelerate the copolymerization reaction. The catalyst can be selected from 0.1% tetrabutyl titanate (TBT) and 0.1% inhibitor. Preferably, after the cooling is completed and the catalyst is added to continue the reaction, the pressure of the reaction environment can be reduced to a vacuum environment (300Pa) and react for 8 hours. And the temperature can be appropriately increased during the reaction to increase the speed of the reaction, so as to complete the copolymerization of the raw materials as soon as possible to prepare the prefabricated elastomer.

[0112] Furthermore, in the above step S13, obtaining the piezoelectric elastomer after sequential precipitation and drying treatment specifically includes:

[0113] After adding an excess of cold methanol to the solution after the prefabricated elastomer is dissolved, the solution is allowed to stand and filtered in turn to obtain a precipitated sample, and the precipitated sample is dried at 50-60°C to obtain a piezoelectric elastomer. It is understandable that after the prefabricated elastomer is prepared, the solution after the prefabricated elastomer is dissolved can be used, wherein the solution is a chlorinated hydrocarbon solution. For example, the solution can be a dichloromethane or trichloromethane solution. It should be understood that the solution can fully dissolve the prefabricated elastomer, which is convenient for removing the raw monomers and oligomers that are not involved in the polymerization in the prefabricated elastomer. Further, after dissolution, an excess of cold methanol can be added to the solution, and the solution is allowed to stand and precipitate first, and the precipitated sample can be obtained by filtering after precipitation. Further, the precipitated sample can be dried at 50-60°C to obtain an uncrosslinked piezoelectric elastomer, which is simple to operate.

[0114] Specifically, in the above step S5, attaching the piezoelectric fiber film to the fiber skeleton specifically includes:

[0115] S51, providing a first syringe, providing a second syringe and a collector;

[0116] S52, dissolving the piezoelectric elastomer in the first solution and adding the solution into the first syringe;

[0117] S53, dissolving the polylactic acid fiber in the second solution and adding the solution into the second syringe;

[0118] S54, the first syringe and the second syringe simultaneously perform electrostatic spinning under the action of a voltage of 10 to 12 kV, and the discharged piezoelectric fiber film adheres to the surface of the discharged fiber skeleton in the collector;

[0119] The piezoelectric fiber film and the fiber skeleton are both mesh structures.

[0120] Specifically, the first syringe and the second syringe are both composed of a roller, a piston and a needle tip. A needle tip is arranged at one end of the roller and a piston is arranged at the other end. The roller is used to contain liquid, and a channel connected to the needle tip is arranged on its inner wall. The piston can move in the roller to push the liquid to be discharged from the needle tip through the channel.

[0121] Exemplarily, 0.6g of piezoelectric elastomer is provided to be dissolved in 6mL of dichloromethane (DSC), and the dichloromethane is stirred at room temperature for 12h to obtain a uniform solution. The uniform solution is transferred to a second syringe of 10mL, the needle tip is connected to a high-voltage power supply, and the drum is grounded. The flow rate of the solution in the second syringe is set to 1mL / h, the distance between the syringe needle and the collector is set to 15cm, the voltage value is set to 11.5kV, and the piston is pushed to start spinning to discharge the fiber skeleton. Further, 0.6g of piezoelectric elastomer is provided to be dissolved in a mixed solution of 6mL of dichloromethane (DSC) and N, N-dimethylformamide (DMF), and the mixed solution is stirred at room temperature for 12h to obtain a uniform solution. The uniform solution is transferred to a first syringe of 10mL, the needle tip is connected to a high-voltage power supply, and the drum is grounded. The flow rate of the solution in the first syringe was set to 1 mL / h, the distance between the syringe needle and the collector was set to 15 cm, the voltage value was set to 11.5 kV, and the piston was pushed to start spinning and discharge the piezoelectric fiber film so that the discharged piezoelectric fiber film adhered to the surface of the fiber skeleton.

[0122] Please join us Figure 2 , Figure 2 The thicker mesh fibers are fiber skeletons, and the thinner mesh fibers are piezoelectric fiber films. The fiber skeletons and piezoelectric fiber films make the prepared medical repair materials have lower elastic modulus and better tensile strength.

[0123] It should be noted that the electrospinning process can be performed by the first syringe and the second syringe at the same time, or the first syringe can be used to perform electrospinning first, and then the second syringe can be used to perform electrospinning first. The second syringe can also be used to perform electrospinning first, and then the first syringe can be used to perform electrospinning first. As long as the final result is that the piezoelectric fiber film is attached to the surface of the fiber skeleton, the specific process is not limited.

[0124] It can be understood that the collector is used to collect the fiber skeleton and piezoelectric fiber film of the mesh structure. The formed piezoelectric fiber film and fiber skeleton are both mesh structures. The piezoelectric fiber film is attached to the surface of the fiber skeleton, and the polylactic acid fiber is a skeleton structure, which can provide a certain support strength. The piezoelectric fiber film provides piezoelectric properties and low elastic modulus. The final medical repair material has good bending and stretching properties, which can solve the problems of insufficient flexibility of existing implants and poor adhesion to the kidney.

[0125] Specifically, the mass ratio of the polylactic acid fiber and the piezoelectric elastomer co-spun yarn in this embodiment ranges from (1:1) to (2:1). The mass ratio of the polylactic acid fiber and the piezoelectric elastomer co-spun yarn is preferably 2:1. Figure 3a , Figure 3a The effect of the mass ratio of polylactic acid fiber and piezoelectric elastomer co-spun yarn on the piezoelectric properties of the final medical repair material is shown. For example, when polylactic acid fiber: piezoelectric elastomer (P: L) = 1:0. That is, without adding piezoelectric elastomer, the voltage generated by the medical repair material is 6.6mV. Polylactic acid fiber: piezoelectric elastomer (P: L) = 2:1. The voltage generated by the medical repair material is 16.6mV. Polylactic acid fiber: piezoelectric elastomer (P: L) = 1:1. The voltage generated by the medical repair material is 7.9mV. Polylactic acid fiber: piezoelectric elastomer (P: L) = 1:2. That is, without adding piezoelectric elastomer, the voltage generated is 12.8mV. Therefore, the mass ratio of polylactic acid fiber and piezoelectric elastomer co-spun yarn is reasonably set so that the final medical repair material has good piezoelectric properties.

[0126] Furthermore, in the above step S5, sequentially performing drying treatment and annealing treatment to obtain the medical repair material includes:

[0127] The fiber skeleton with the piezoelectric fiber film attached thereto is dried as a preform, and then annealed at 130° C. to 140° C. for 50 to 60 minutes. The annealed preform is cooled to room temperature to obtain a medical repair material.

[0128] For example, after electrospinning, the fiber skeleton with the piezoelectric fiber film attached can be taken out from the collector as a preform, and the preform is dried and annealed at 140°C for 60 minutes, and then cooled to room temperature to obtain a medical repair material. The operation is simple and convenient, and the formed medical repair material has good bending and stretching properties.

[0129] In order to solve the above technical problems, the second embodiment of the present invention further provides a medical repair material, which is prepared by the above-mentioned preparation method of the medical repair material.

[0130] It should be understood that the medical repair material provided in this embodiment has a lower elastic modulus, so that it has good bending and stretching properties when used in the biomedical field, and can solve the problem that the existing implants or monitors are not flexible enough and have poor adhesion to the transplanted organs. Exemplarily, it can be used in the field of kidney transplantation to promote the repair of renal tubules in renal ischemia-reperfusion injury. In addition, it can also be used in the medical field of accelerating the healing of wounds, muscle and tendon defects, and its application range is wide.

[0131] See also Figure 3b , Figure 3b This is a schematic diagram of the therapeutic effect of the medical repair material applied in the field of kidney transplantation, where sham is the blank group, IRI is the defect reperfusion injury (kidney injury), and IRI+ES is the recovery effect of the medical repair material after injury. H&E and PAS represent two different staining methods. The more blanks there are, the more necrosis there is in the glomeruli and tubules. It can be seen that on the first day, the kidneys that used the medical repair material were severely damaged, and on the second day, the kidneys that did not use the medical repair material began to be damaged, while the kidneys that used the medical repair material began to be repaired. On the seventh day, the kidneys that did not use the medical repair material were severely damaged, while the kidneys that used the medical repair material were basically repaired. It can be seen that the medical repair material provided in this embodiment can be used to repair transplanted organs, such as kidneys.

[0132] See also Figure 4a , Figure 4aThis is a schematic diagram of the therapeutic effect of medical repair materials in the field of ureteral repair. The vertical coordinates of the three line graphs all represent the number of radionuclides accumulated in the kidney, while the horizontal coordinates represent time. The control group represents the radionuclides accumulation in the left and right kidneys of patients when they are normal. It can be seen that under normal conditions, both kidneys maintain a high level, and the radionuclides show a slight downward trend over time. In the patient ureteral stenosis group, it can be clearly seen that the number of radionuclides accumulated in the left kidney is low due to ureteral stenosis. When the medical repair material is applied to ureteral stenosis, the number of radionuclides accumulated in the left kidney increases due to the electrical stimulation provided by the medical repair material, and the phenomenon of ureteral stenosis is alleviated. The bar graph represents the level of human glomerular filtration rate when the medical repair material is applied to ureteral repair. Sham represents the blank group, which represents the glomerular filtration rate in the human body of the patient in a healthy state. US represents the ureteral stenosis group, and US+ES represents the medical repair material applied to the ureteral stenosis group. It can be seen that under the effect of medical repair materials, the glomerular filtration rate is significantly improved. In addition, it is obvious that there is a statistical difference between the data without the application of medical repair materials and the data with the application of medical repair materials.

[0133] Please also read Figure 4b , Figure 4b This is a schematic diagram of the therapeutic effect of medical repair materials in the field of ureteral repair. The blank group represents the thickness of the ureteral epithelial cells of patients in a healthy state. US represents the ureteral stenosis group, and US+ES represents the medical repair material applied to the ureteral stenosis group. It can be seen that under the action of the medical repair material, the thickness of the ureteral epithelial cells is significantly reduced. In addition, there is no statistical difference in the data of the thickness of the ureteral epithelial cells between the blank group and the medical repair material, and then there is a significant statistical difference in the data of the thickness of the ureteral epithelial cells between the blank group and the medical repair material and the non-medical repair material. It should be noted that the lack of statistical difference means that the difference between the two groups of data does not reach the statistically significant level, that is, the difference does not have enough evidence to support the hypothesis proposed, which may be due to sampling errors rather than research factors. This does not mean that the two groups of data are exactly the same, but that the difference does not reach the statistically significant level.

[0134] Please combine Figure 4c , Figure 4cIt is a schematic diagram of the therapeutic effect of medical repair materials in the field of ureteral repair. The blank group represents the amount of collagen deposition in the patient in a healthy state. US represents the amount of collagen deposition in the ureteral stenosis group, and US+ES represents the amount of collagen deposition in the ureteral stenosis group with medical repair materials. It can be seen that the thickness of collagen deposition is significantly reduced under the action of medical repair materials. In addition, there is no statistical difference in the data of collagen deposition in the blank group and the ureter with medical repair materials applied, and then there is a significant statistical difference in the data of collagen deposition in the blank group and the ureter with medical repair materials applied and the data of collagen deposition in the ureteral stenosis without medical repair materials applied. It should be understood that after the medical repair material is applied to ureteral stenosis, the thickness of ureteral epithelial cells is significantly reduced, indicating that the patient's ureter is not so obstructed and the degree of fibrosis is lighter. In addition, the significant reduction in the thickness of collagen deposition also reduces the degree of fibrosis of the surface ureter, which is helpful for the repair of ureteral trauma in patients.

[0135] It should be noted that the medical repair material provided in this embodiment can be applied to the fields of skin wound repair, muscle repair, defective tendon repair, ureter repair, urethra repair, bladder repair or organ repair to be transplanted. Its application range is relatively wide. It can fill the gap in the existing medical field that lacks corresponding means to repair human organs, such as ureter, urethra repair, bladder or kidney to be transplanted.

[0136] The medical repair material provided in the embodiment of the present invention has the same beneficial effects as the above-mentioned method for preparing the medical repair material, which will not be described in detail here.

[0137] In order to solve the above technical problems, the third embodiment of the present invention further provides a medical transplant bag 1, including a main body 11 and at least two connecting lines 12, the main body 11 is provided with a signal input port 13 and a signal output port 14, the connecting line 12 is used to connect the signal input port 13 with an external monitoring device and to connect the signal output port 14 with an external monitoring device, and the material of the main body 11 is the above-mentioned medical repair material.

[0138] It can be understood that when the medical transplant bag 1 is attached to the surface of the organ to be transplanted, it can continuously receive the physiological state information of the organ in the process of generating piezoelectric signals, and convert the physiological state information into electrical signals. The signal input port 13 and the signal output port 14 are electrically connected to the external monitoring device through the connecting line 12, and the signal output port 14 is connected to the external monitoring device. The electrical signal connecting line 12 is transmitted to the external monitoring device, so that the doctor can monitor the patient in real time.

[0139] The medical transplant bag 1 provided in the embodiment of the present invention has the same beneficial effects as the above-mentioned method for preparing a medical repair material, which will not be described in detail here.

[0140] The above is a detailed introduction to a medical repair material, a preparation method and a medical transplant bag disclosed in an embodiment of the present invention. Specific examples are used herein to illustrate the principle and implementation mode of the present invention. The description of the above embodiments is only used to help understand the method of the present invention and its core idea. At the same time, for a person skilled in the art, according to the idea of ​​the present invention, there will be changes in the specific implementation mode and the scope of application. In summary, the content of this specification should not be understood as a limitation on the present invention. Any modifications, equivalent substitutions and improvements made within the principles of the present invention should be included in the protection scope of the present invention.

Claims

1. A method for preparing a medical repair material, characterized in that: The following steps are involved: Providing piezoelectric elastomers and polylactic acid fibers; Providing a dichloromethane solution and an N,N-dimethylformamide solution, and using a solution obtained by mixing the dichloromethane and the N,N-dimethylformamide as a first solution; providing a dichloromethane solution, using dichloromethane as a second solution; The piezoelectric elastomer is dissolved in a first solution and subjected to an electrospinning process to form a piezoelectric fiber film, and the polylactic acid fiber is dissolved in a second solution and subjected to an electrospinning process to form a fiber skeleton; The piezoelectric fiber film is attached to the fiber skeleton and then subjected to drying and annealing treatments in sequence to obtain the medical repair material.

2. The method for preparing the medical repair material according to claim 1, characterized in that: The elastic modulus of the medical repair material is 0.1-3 Mpa.

3. The method for preparing the medical repair material according to claim 1, characterized in that: Providing a piezoelectric elastomer comprises the following steps: providing butanediol, lactic acid, sebacic acid and itaconic acid as raw materials; The raw materials are mixed and reacted to obtain a preformed elastomer; The prefabricated elastomer is dissolved by chlorinated hydrocarbon, and then precipitated and dried to obtain the piezoelectric elastomer.

4. The method for preparing the medical repair material according to claim 3, characterized in that: The molar ratio of hydroxyl group to carboxyl group in the preformed elastomer is (1.5-1):1, and the molar ratio of itaconic acid to carboxyl group in the preformed elastomer is 1:(8-12).

5. The method for preparing the medical repair material according to claim 3, characterized in that: The mixing reaction of the raw materials specifically comprises: The raw materials are mixed and reacted at a first temperature for a first time, and then the temperature is raised to a second temperature for a second time. After reacting at the second temperature for a second time, the temperature is lowered to a third temperature, and after the temperature is lowered, a catalyst is added to react for a third time to obtain a prefabricated elastomer; Among them, the second temperature>the first temperature>the third temperature.

6. The method for preparing a piezoelectric fiber film according to claim 3, characterized in that: The piezoelectric elastomer obtained after sequential precipitation and drying treatments specifically includes: Adding excess cold methanol to the solution after the prefabricated elastomer is dissolved, the solution is allowed to stand and filtered in sequence to obtain a precipitated sample, and the precipitated sample is dried at 50-60° C. to obtain the piezoelectric elastomer.

7. The method for preparing the medical repair material according to claim 1, characterized in that: Attaching the piezoelectric fiber film to the fiber skeleton specifically includes: providing a first syringe, providing a second syringe and a collector; Dissolving the piezoelectric elastomer in the first solution and then adding the solution into the first syringe; Dissolving polylactic acid fiber in the second solution and adding the solution into the second syringe; The first syringe and the second syringe simultaneously perform electrostatic spinning under the action of a voltage of 10 to 12 kV, and the discharged piezoelectric fiber film adheres to the surface of the discharged fiber skeleton in the collector; The piezoelectric fiber film and the fiber skeleton are both mesh structures.

8. The method for preparing the medical repair material according to claim 1, characterized in that: The drying process and annealing process are performed in sequence to obtain the medical repair material including: The fiber skeleton with the piezoelectric fiber film attached thereto is dried as a preform, and then annealed at 130° C. to 140° C. for 50 to 60 minutes. The annealed preform is cooled to room temperature to obtain a medical repair material.

9. A medical repair material, characterized in that: The medical repair material is prepared by the preparation method of the medical repair material according to any one of claims 1 to 8.

10. A medical transplant bag, characterized in that: It comprises a main body and at least two connecting wires, wherein the main body is provided with a signal input port and a signal output port, wherein the connecting wires are used to connect the signal input port with an external monitoring device and to connect the signal output port with an external monitoring device, and wherein the material of the main body is the medical repair material described in claim 9.

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