Preparation method of polymer artificial heart valve composite material

Abstract

The invention provides a preparation method of a polymer artificial heart valve composite material, which comprises the following steps: immersing a fabric with a first polymer layer on the surface into a poor solvent, and paving the fabric on a substrate, so that when the first polymer layer is in contact with a second polymer solution, the first polymer layer is only slightly dissolved; forming a coating formed by embedding the first polymer layer and the second polymer layer on the surface of the fabric under the action that the poor solvent prevents the second polymer solution from entering the fabric; meanwhile, after the fabric is immersed in the poor solvent, the adsorption of the fabric to the second polymer solution is reduced, so that the fabric is kept flat in the composite material, the internal structure of the composite material is uniform, and the stability of the composite material is enhanced. By means of the mode, the polymer artificial heart valve composite material which is uniform in internal structure and smooth and flat in surface is prepared.

Description

Technical Field

[0001] The present invention relates to the technical field of medical devices, and particularly to a preparation method of a polymer artificial heart valve composite material. Background Art

[0002] In existing research, the leaflet materials of textile-based artificial heart valves are generally pure fabrics composed of polymer fibers / yarns or materials compounded with fabric bases. However, pure fabrics have problems such as leakage, easy structural deformation, and rough surfaces that are prone to thrombus formation. For the composite materials obtained by combining with polymers, the leakage amount is reduced, the structural stability is improved, and the roughness is improved, which has advantages over pure fabrics in the blood use environment. However, when preparing a polymer layer on the fabric surface, due to the low mechanical strength of the fabric itself, it is easy to cause uneven internal structure of the composite material, resulting in poor material performance.

[0003] In the prior art, in a patent document with the application number CN202111316032.9, the publication date of May 9, 2023, and the title of "A Polymer Valve, Valve Assembly and Its Preparation Method", by preparing a transition layer and a coating on the base layer and using the chemical bonding action between the base layer and the transition layer, and between the transition layer and the coating to combine the various layer structures together, the stability of the material is good. However, the above method of combining the layers by using the chemical bonding action between the layer structures has strict requirements for material selection, and it is difficult to control the smoothness of the material surface, increasing the difficulty of preparation, so it is not suitable for mass production.

[0004] In view of this, it is necessary to design an improved preparation method of a polymer artificial heart valve composite material to solve the above problems. Summary of the Invention

[0005] The purpose of the present invention is to provide a preparation method of a polymer artificial heart valve composite material.

[0006] To achieve the above invention purpose, the present invention provides a preparation method of a polymer artificial heart valve composite material, including the following steps:

[0007] Immerse the fabric in the first polymer solution, and after the first drying, obtain a fabric with the first polymer layer on both sides;

[0008] Coat the second polymer solution on the surface of a smooth substrate;

[0009] After dipping the fabric with the first polymer layer into a poor solvent, a second polymer layer is formed on the surface of at least one of the first polymer layers: the fabric is laid flat on a substrate, and one of the first polymer layers on the fabric surface is brought into contact with the second polymer solution; after secondary drying, a second polymer layer is formed on the surface of one of the first polymer layers, and the surface of the second polymer layer away from the first polymer layer is smooth. The poor solvent can promote the interpenetration of the contact surfaces of the first polymer layer and the second polymer layer.

[0010] Preferably, the mass concentration of the first polymer solution is 1-15 w / v%; the thickness of the first polymer layer is less than 10 μm.

[0011] Preferably, the mass volume fraction of the second polymer solution is 5-30%; the coating thickness of the second polymer solution is 100-1000 μm.

[0012] Preferably, the poor solvent is water, alcohols or ketones.

[0013] Preferably, the first polymer solution is obtained by dissolving a first polymer in a first organic solvent. The first polymer is one or more of polyurethane, polycarbonate-polyurethane copolymer, polysiloxane-polyurethane copolymer, styrene / isobutene copolymer; the first organic solvent is one or more of N,N-dimethylformamide, N,N-dimethylacetamide, dimethyl sulfoxide, tetrahydrofuran, dioxane, chloroform, dichloromethane, hexafluoroisopropanol, dioxolane.

[0014] Preferably, the second polymer solution is obtained by dissolving a second polymer in a second organic solvent. The second polymer is one or more of polyurethane, polycarbonate-polyurethane copolymer, polysiloxane-polyurethane copolymer, styrene / isobutene copolymer, and the second organic solvent is one or more of N,N-dimethylformamide, N,N-dimethylacetamide, dimethyl sulfoxide, tetrahydrofuran, dioxane, chloroform, dichloromethane, hexafluoroisopropanol, dioxolane.

[0015] Preferably, before dipping the fabric into the first polymer solution, the fabric needs to be subjected to plasma treatment. The conditions of the plasma treatment are: treatment power 50-300 W, treatment time 30-300 s, and the gas environment is one of oxygen, hydrogen, air, argon, helium.

[0016] Furthermore, the present invention also prepares a polymer artificial heart valve composite material by using the above preparation method of the polymer artificial heart valve composite material.

[0017] Specifically, the polymer artificial heart valve composite material includes:

[0018] Fabric;

[0019] Two first polymer layers, which are respectively disposed on both sides of the fabric;

[0020] At least one second polymer layer, which is disposed on the surface of at least one of the first polymer layers, and the contact surfaces of the first polymer layer and the second polymer layer are interlocked, and the surface roughness of the side of the second polymer layer away from the first polymer layer is 80 - 150 nm.

[0021] In particular, the polymer artificial heart valve composite material prepared by the present invention can be applied in the field of heart valves.

[0022] The beneficial effects of the present invention are as follows:

[0023] 1. For the preparation method of the polymer artificial heart valve composite material provided by the present invention, after immersing the fabric with the first polymer layer on its surface into a poor solvent, it is then laid flat on a substrate to make the first polymer layer contact with the second polymer solution. Since the first polymer layer will be slightly soluble when contacting the second polymer solution after being immersed in the poor solvent, and the poor solvent can, to a certain extent, hinder the penetration of the second polymer solution into the fabric interior, keeping the fabric flat in the composite material, ensuring the uniform internal structure of the composite material, and enhancing the stability of the composite material. Under the combined action of the above two, it promotes the interlocking between the first polymer layer and the second polymer layer, making the two layer structures stably connected together.

[0024] 2. For the preparation method of the polymer artificial heart valve composite material provided by the present invention, by using a substrate with a relatively low surface roughness and further preparing a second polymer layer on the fabric surface, it ensures that the surface of the prepared composite material is flat and smooth. When using this material as a valve material, it reduces the possibility of deposition of blood cells, etc. on it, effectively avoiding the occurrence of thrombus phenomenon. In particular, the present invention also precisely controls the thickness of the coating by regulating the concentrations of the two polymer solutions and the coating thickness of the second polymer, ensuring that the composite material has good opening and closing properties. Description of the Drawings

[0025] Figure 1 It is the surface electron micrograph of the composite material prepared in Example 1 of the present invention;

[0026] Figure 2 It is the cross-sectional electron micrograph of the composite material prepared in Example 1 of the present invention;

[0027] Figure 3 It is the cross-sectional electron micrograph of the composite material prepared in Comparative Example 1 of the present invention;

[0028] Figure 4Cross-sectional electron micrograph of the composite material prepared in Comparative Example 2 of the present invention. Detailed implementation manners

[0029] In order to make the objectives, technical solutions and advantages of the present invention clearer, the present invention will be described in detail below with reference to the accompanying drawings and specific embodiments.

[0030] Here, it should also be noted that in order to avoid obscuring the present invention due to unnecessary details, only the structures and / or processing steps closely related to the solution of the present invention are shown in the drawings, while other details less related to the present invention are omitted.

[0031] In addition, it should also be noted that the term "comprising", "including" or any other variant thereof is intended to cover non-exclusive inclusion, so that a process, method, article or device including a series of elements not only includes those elements, but also includes other elements not expressly listed, or further includes elements inherent to such process, method, article or device.

[0032] One aspect of the present invention provides a polymer artificial heart valve composite material, comprising:

[0033] Fabric;

[0034] Two first polymer layers, which are respectively disposed on both sides of the fabric;

[0035] At least one second polymer layer, which is disposed on the surface of the first polymer layer, and the contact surfaces of the first polymer layer and the second polymer layer are interlocked, and the surface roughness of the side of the second polymer layer away from the first polymer layer is 80 - 150 nm.

[0036] On the other hand, the present invention also provides a preparation method of the above polymer artificial heart valve composite material, comprising the following steps:

[0037] Immerse the fabric in the first polymer solution, and after the first drying, obtain a fabric with the first polymer layer on both sides;

[0038] Coat the second polymer solution on the surface of the substrate;

[0039] After dipping the fabric with the first polymer layer into a poor solvent, it is laid flat on a substrate to make the first polymer layer contact with the second polymer solution, and then dried for the second time to form a second polymer layer on the surface of the first polymer layer. The surface of the second polymer layer away from the first polymer layer is smooth. During the drying process, under the action of the poor solvent, the contact surface between the first polymer layer and the second polymer layer is interpenetrated, and a polymer artificial heart valve composite material is obtained. It should be noted that in some other embodiments, the second polymer layer can also be prepared on the surface of another first polymer layer by the above method, that is, the number of the second polymer layers in the composite material can be selected according to needs.

[0040] Preferably, the fabric is a woven fabric, a knitted fabric or a non-woven fabric; the material of the fabric is one or more of polyester, polyethylene, polypropylene, polyamide and polyvinyl chloride.

[0041] Preferably, before dipping the fabric into the poor solvent, the fabric needs to be treated by plasma. The fabric treated in this way is more conducive to the poor solvent entering the interior of the fabric; among them, the conditions for plasma treatment are a treatment power of 50-300 W, a treatment time of 30-300 s, and the gas environment includes but is not limited to one of oxygen, hydrogen, air, argon, and helium.

[0042] Preferably, the first polymer solution is obtained by dissolving the first polymer in the first organic solvent. The mass concentration of the first polymer solution is 1-15 w / v%. The contact time of the fabric in the first polymer solution is 0.5-30 min; the first polymer is one or more of polyurethane, polycarbonate-polyurethane copolymer, polysiloxane-polyurethane copolymer, and styrene / isobutene copolymer, and the first organic solvent is one or more of N,N-dimethylformamide, N,N-dimethylacetamide, dimethyl sulfoxide, tetrahydrofuran, dioxane, chloroform, dichloromethane, hexafluoroisopropanol, and dioxolane.

[0043] Preferably, the temperature of the first drying is 40-80 °C and the time is 1-120 min.

[0044] Preferably, the second polymer solution is obtained by dissolving a second polymer in a second organic solvent, and the mass-volume fraction of the second polymer solution is 5-30%; the second polymer is one or more of polyurethane, polycarbonate-polyurethane copolymer, polysiloxane-polyurethane copolymer, and styrene / isobutylene copolymer, and the second organic solvent is one or more of N,N-dimethylformamide, N,N-dimethylacetamide, dimethyl sulfoxide, tetrahydrofuran, dioxane, chloroform, dichloromethane, hexafluoroisopropanol, and dioxolane. In the above process, by selecting a polymer that is the same as or similar in properties to the first polymer layer to form the second polymer solution, better compatibility is achieved between the first polymer layer and the second polymer solution, which is conducive to forming an interpenetrating structure between the two, enhancing the stability inside the coating and between the coating and the fabric.

[0045] Preferably, the temperature of the second drying is 40-80 °C and the time is 6-48 h.

[0046] Preferably, the thickness of the first polymer layer is below 10 μm, and the coating thickness of the second polymer solution is 100-1000 μm. By controlling the above conditions, the coating thickness on the fabric surface can be regulated, and the influence of the coating on the softness of the fabric itself can be minimized as much as possible.

[0047] Preferably, the methods for coating the second polymer solution include, but are not limited to, knife coating, spin coating, roll coating, and flow coating.

[0048] Preferably, the poor solvents include, but are not limited to, water, alcohols, and ketones, such as ethanol, isopropanol, and acetone, and both the first polymer and the second polymer are not easily soluble in the poor solvent.

[0049] Preferably, the substrate material includes, but is not limited to, glass, metal, and silica gel.

[0050] The following further illustrates the preparation method of the polymer artificial heart valve composite material proposed by the present invention in combination with specific examples:

[0051] Example 1

[0052] The polyester woven fabric used in this example was purchased from Suzhou Zhixian Technology Co., Ltd.

[0053] In this example, a polymer artificial heart valve composite material was prepared. The specific preparation method includes the following steps:

[0054] S1: After subjecting the polyester woven fabric to plasma treatment, it was immersed in a tetrahydrofuran solution of polyurethane with a concentration of 10 w / v% (i.e., the mass of the solute per unit volume of the solution) for 3 min, taken out and dried at 60 °C for 5 min to obtain a fabric with a first polymer layer on both surfaces;

[0055] S2: Using the spin coating method, a dimethyl sulfoxide solution of polyurethane with a mass - volume fraction of 15% was coated on a glass substrate; the fabric with the first polymer layer was immersed in ethanol and taken out, then laid flat on the above - treated glass substrate and dried at 70 °C for 12 h to form a second polymer layer on one side of the fabric with the first polymer layer. Then, the other side of the fabric with the first polymer layer was laid flat on the glass substrate coated with the dimethyl sulfoxide solution of polyurethane with a mass - volume fraction of 15% and dried at 70 °C for 12 h to prepare a second polymer layer on the other side of the fabric with the first polymer layer, obtaining a polymer artificial heart valve composite material.

[0056] The electron micrograph of the composite material prepared in this example is as Figure 1 and 2 shown. It can be seen from the figure that the surface of the composite material is flat and smooth, and the internal structure of the composite material is uniform, and no obvious interfacial delamination appears inside the coating.

[0057] To explore the stiffness and roughness of the composite material prepared in this example, the following method was used for testing. First, the composite material and the fabric were cut into circular pieces with a diameter of 40 mm, and then placed on a paper softness tester to measure the four angles of the circular pieces respectively, and calculate the average value of stiffness; then the composite material and the fabric were cut into square pieces with a size of 1 cm×1 cm, fixed on the electron microscope stage through conductive glue, and put into the electron microscope chamber for microscopic observation; select the roughness test field of view, start the 3Droughness plug - in, conduct roughness testing, and calculate the average value of surface roughness Ra.

[0058] Examples 2 to 5

[0059] The differences between Examples 2 to 5 and Example 1 are only that: the concentration of the first polymer solution is different from that of Example 1, and the other steps are basically the same as those of Example 1, so they will not be elaborated here. The performance comparisons of the composite materials prepared under the first polymer solution concentrations and corresponding conditions in Examples 1 to 5 are shown in Table 1. It can be seen from the table that as the concentration of the first polymer solution increases, the increase amplitude of the fabric stiffness also increases. The reason is that as the polymer solution concentration increases, the amount of polymer loaded on the fabric increases.

[0060] Table 1 Performance comparison of the composite materials prepared under the first polymer solution concentrations and corresponding conditions in Examples 1 to 5

[0061]

[0062]

[0063] Examples 6 to 9

[0064] Examples 6 to 9 are different from Example 1 only in that: the concentration of the second polymer solution is different from that in Example 1, and the other steps are basically the same as those in Example 1, which will not be elaborated here. The performance comparison of the composite materials prepared under the concentration of the second polymer solution and the corresponding conditions in Example 1 and Examples 6 to 9 is shown in Table 2. It can be seen from the table that as the polymer concentration increases, the stiffness of the composite material gradually increases (i.e., the softness gradually decreases), while the surface roughness gradually decreases.

[0065] Table 2 Performance comparison of the composite materials prepared under the concentration of the second polymer solution and the corresponding conditions in Example 1 and Examples 6 to 9

[0066]

[0067] Examples 10 to 13

[0068] Examples 10 to 13 are different from Example 1 only in that: the coating thickness of the second polymer solution is different from that in Example 1, and the other steps are basically the same as those in Example 1, which will not be elaborated here. The performance comparison of the composite materials prepared under the coating thickness of the second polymer solution and the corresponding conditions in Example 1 and Examples 10 to 13 is shown in Table 3. It can be seen from the table that within the coating thickness range of the second polymer solution given in the present invention, composite materials with both softness and low surface roughness can be prepared.

[0069] Table 3 Performance comparison of the composite materials prepared under the coating thickness of the second polymer solution and the corresponding conditions in Example 1 and Examples 10 to 13

[0070]

[0071] Comparative Example 1

[0072] Comparative Example 1 is different from Example 1 only in that: the composite material is not prepared by the method of first preparing the first polymer layer on the fabric surface in Example 1 and then contacting it with the second polymer solution on the substrate surface. Instead, the second polymer solution is first coated on the substrate surface, then the first polymer solution is coated, and finally the fabric is placed on the surface of the first polymer solution. The coating thickness of the second polymer solution and the usage amount of the first polymer solution in Comparative Example 1 are the same as those in Example 1, and the other process parameters are basically the same as those in Example 1, which will not be elaborated here.

[0073] The cross-sectional electron micrograph of the composite material prepared by the above method is as Figure 3 shown, and comparing it with Figure 2By comparison, it can be seen that no obvious delamination appears inside the coating in the figure, but the fabric in the composite material is uneven. The reason is as follows: When preparing by the method of Comparative Example 1, since the first polymer layer is not formed on the surface of the fabric, the fabric still remains soft on the surface. When contacting with the polymer solution, as the solution penetrates into the fabric interior, the fabric collapses to a certain extent; while in Example 1, the first polymer layer is first prepared on the surface of the fabric, and after being immersed in the poor solvent, it is then laid flat on the substrate. Since the surface of the fabric is modified by the first polymer layer and has a certain strength, and after being immersed in the poor solvent, it will have a certain softness, avoiding the collapse of the fabric caused by the penetration of the second polymer solution into the fabric interior after placing the fabric on the substrate. Under the above two effects, a composite material with a uniform internal structure is obtained, endowing the material with stability.

[0074] Comparative Example 2

[0075] The difference between Comparative Example 2 and Example 1 lies in that: the fabric is not immersed in the poor solvent but laid flat on the surface of the substrate. The specific preparation process is as follows: The second polymer solution is coated on the substrate, and then the fabric with the first polymer layer formed on its surface is laid flat on the substrate. The coating amount of the second polymer solution and the thickness of the first polymer layer are the same as those in Example 1, and other process parameters are basically the same as those in Example 1, which will not be elaborated here.

[0076] The cross-sectional electron micrograph of the composite material prepared in Comparative Example 2 is as Figure 4 shown. Comparing it with Figure 2 it can be seen that obvious delamination appears inside the coating of the composite material prepared in Comparative Example 2, the fabric in the composite material is uneven, and there are voids between the fabric and the coating. The reason is as follows: In the preparation process of Example 1, the presence of the poor solvent can not only effectively promote the precipitation and curing of the second polymer in the second polymer solution on the surface of the first polymer, but also promote the fusion of the precipitated second polymer with the first polymer layer, finally forming a structure in which the first polymer layer and the second polymer layer are intercalated with each other, and there is almost no interface between the two layer structures; while when the fabric with the first polymer layer is not treated with the poor solvent, the second polymer solution directly contacts the first polymer layer, and it is easy to introduce air bubbles and an obvious contact interface between the two.

[0077] The above embodiments are only used to illustrate the technical solutions of the present invention and not to limit them. Although the present invention has been described in detail with reference to the preferred embodiments, those of ordinary skill in the art should understand that the technical solutions of the present invention can be modified or equivalently replaced without departing from the spirit and scope of the technical solutions of the present invention.

Claims

1. A preparation method of a composite material for a polymeric artificial heart valve, characterized in that, It includes the following steps: Immerse the fabric in the first polymer solution, and after the first drying, obtain a fabric with the first polymer layers on both sides; Coat the second polymer solution on the surface of a smooth substrate; After immersing the fabric with the first polymer layer in a poor solvent, form a second polymer layer on the surface of at least one of the first polymer layers: lay the fabric flat on the substrate so that one of the first polymer layers on the fabric surface contacts the second polymer solution; then after the second drying, form a second polymer layer on the surface of one of the first polymer layers, and the surface of the second polymer layer away from the first polymer layer is smooth, and the poor solvent can promote the interpenetration of the contact surfaces of the first polymer layer and the second polymer layer.

2. The preparation method of the polymer artificial heart valve composite material according to claim 1, characterized in that, The mass concentration of the first polymer solution is 1-15 w / v%; the thickness of the first polymer layer is below 10 μm.

3. The preparation method of the polymer artificial heart valve composite material according to claim 2, characterized in that, The mass-volume fraction of the second polymer solution is 5-30%; the coating thickness of the second polymer solution is 100-1000 μm.

4. The preparation method of the polymer artificial heart valve composite material according to claim 3, characterized in that, The poor solvent is water, alcohols or ketones.

5. The preparation method of the polymer artificial heart valve composite material according to claim 2, wherein The first polymer solution is obtained by dissolving a first polymer in a first organic solvent, and the first polymer is one or more of polyurethane, polycarbonate-polyurethane copolymer, polysiloxane-polyurethane copolymer, styrene / isobutylene copolymer; the first organic solvent is one or more of N,N-dimethylformamide, N,N-dimethylacetamide, dimethyl sulfoxide, tetrahydrofuran, dioxane, chloroform, dichloromethane, hexafluoroisopropanol, dioxolane.

6. The preparation method of the polymer artificial heart valve composite material according to claim 5, characterized in that, The second polymer solution is obtained by dissolving a second polymer in a second organic solvent, and the second polymer is one or more of polyurethane, polycarbonate-polyurethane copolymer, polysiloxane-polyurethane copolymer, styrene / isobutylene copolymer, and the second organic solvent is one or more of N,N-dimethylformamide, N,N-dimethylacetamide, dimethyl sulfoxide, tetrahydrofuran, dioxane, chloroform, dichloromethane, hexafluoroisopropanol, dioxolane.

7. The preparation method of the polymer artificial heart valve composite material according to claim 6, characterized in that, Before immersing the fabric in the first polymer solution, the fabric needs to be subjected to plasma treatment, and the conditions of the plasma treatment are: treatment power 50-300 W, treatment time 30-300 s, and the gas environment is one of oxygen, hydrogen, air, argon, helium.

8. A polymer artificial heart valve composite material prepared by the preparation method according to any one of claims 1-7.

9. The polymer artificial heart valve composite material according to claim 8, wherein, It includes: Fabric; Two first polymer layers, which are respectively arranged on both sides of the fabric; At least one second polymer layer, which is arranged on the surface of at least one of the first polymer layers, and the contact surfaces of the first polymer layer and the second polymer layer are interpenetrated, and the surface roughness of the side of the second polymer layer away from the first polymer layer is 80-150 nm.

10. Use of the polymer artificial heart valve composite material according to claim 8 or 9 in the preparation of a heart valve.

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