High-molecular artificial heart valve and preparation method therefor

Abstract

Disclosed herein are a high-molecular artificial heart valve and a preparation method therefor, relating to the technical field of medical instruments. The high-molecular artificial heart valve comprises a frame, a skirt arranged on the surface of the frame, and valve leaflets bonded with the skirt. The preparation method therefor comprises the following steps: after the skirt is prepared on the frame, arranging a part of the valve leaflets on the surface of at least a part of the edge of the skirt, or connecting the edges of the valve leaflets with the at least a part of the skirt, and then bonding the valve leaflets with the edge of the skirt by means of interface microtreatment. The interface microtreatment is achieved by means of a polymer solution that bonds the valve leaflets with the edge of the skirt or by utilizing thermal bonding between the valve leaflets and the edge of the skirt. The valve prepared by the method has the advantages of uniform structure and high strength, effectively improving the production quality of the valve.

Description

A polymer artificial heart valve and its preparation method Technical Field

[0001] This article relates to the field of medical device technology, and in particular to a polymer artificial heart valve and a preparation method thereof. Background Art

[0002] This article claims priority to Chinese patent application number 2023117984628, filed on December 25, 2023, entitled “A method for preparing a polymer artificial heart valve composite material”, and Chinese patent application number 2023118524424, filed on December 29, 2023, entitled “A method for molding a polymer artificial heart valve”, all contents of which are incorporated herein by reference.

[0003] Transcatheter prosthetic heart valve replacement is an effective minimally invasive treatment for structural valvular heart disease. Compared to traditional open-chest surgical valve replacement, this procedure offers significant advantages such as less trauma, shorter operative time, and faster postoperative recovery, leading to rapid adoption. The prosthetic valve used in this procedure consists of artificial valve leaflets, a metal stent, and a leak-proof skirt. The leaflets and stent are attached via an attachment flange, and the skirt completely covers the stent. The leaflets of invasive prosthetic heart valves are primarily made from animal-derived tissue, such as bovine pericardium, porcine pericardium, and porcine heart valves. This is not only costly but also difficult to control for material consistency. Furthermore, due to the structural characteristics of animal-derived tissue, these leaflets can only be attached to the metal stent through manual suturing, which requires significant labor costs. The average sewing time for commercially available invasive prosthetic valves is approximately three days, and the skilled suturing technicians are highly skilled. Furthermore, manual valve sewing can make product quality difficult to control and reduce product consistency.

[0004] Polymer leaflets, with their excellent durability, compatibility, and stability, are considered promising candidates for the manufacture of next-generation invasive prosthetic heart valves. These valves are typically manufactured using either a single-piece dip-coating process or by first preparing the leaflets and skirt and then combining them for molding. Valves manufactured using single-piece dip-coating are highly efficient, but they lack the ability to tailor the material to the specific application. Separately preparing the leaflets and skirt and then suturing them together can lead to inflammation, hyperplasia, and calcification at the suture site.

[0005] In view of the above, this paper describes polymeric prosthetic heart valves and methods for their preparation that address some or all of these problems. Summary of the Invention

[0006] This article describes a method for preparing a polymer artificial heart valve, comprising the following steps:

[0007] Prepare a skirt on the bracket;

[0008] Placing a portion of the leaflet on the surface of at least a portion of the skirt or butting the edge of the leaflet against at least a portion of the skirt, wherein both the leaflet and the skirt are made of polymer materials; bonding the leaflet and the edge of the skirt together by interface micro-processing, and drying to obtain the polymer artificial heart valve;

[0009] The interface micro-processing is achieved by bonding the edges of the leaflet and the skirt with the help of a polymer B solution or by utilizing thermal bonding between the leaflet and the skirt. The polymer B solution has a viscosity of 300-300,000 centipoise and a solid content of 5-30%.

[0010] In some embodiments, the method for preparing a skirt on a stent includes directly forming a skirt integrally connected to the stent by dipping, or fixing a prefabricated skirt to the stent. The method for preparing a skirt by dipping includes the following steps: dipping the stent into a 10-20% by mass solution of polymer A, dipping and pulling at a pulling speed of 1000-1200 mm / s, drying at 50-60°C for 4-5 hours, and then dipping a second time at a pulling speed of 1000-1200 mm / s. After dipping, the stent is dried at 50-60°C for 48-60 hours to obtain the skirt on the stent surface.

[0011] In some embodiments, the method for bonding the leaflet and the skirt together using the polymer B solution is one or more of a solution dipping method, a solution dispensing method, and a solution spraying method; the thermal bonding method is one or more of a thermal welding method, a laser welding method, and an infrared welding method; and the width of the bonding area between the leaflet and the skirt is 1000-1200 μm. When the solution dipping method is used to bond the leaflet and the skirt, the pulling speed during the dipping process is 1-10000 μm / s. When the solution dispensing method is used, the glue discharge pressure is 40-60 psi; when the solution spraying method is used, the viscosity of the polymer B solution is 1-100 centipoise, and the solid content of the solution is 1-20%.

[0012] In some embodiments, the process of bonding the leaflets and the skirt is performed using a clamping mold. The clamping mold includes a support member for supporting the stent. The support member comprises a cylindrical body with a smooth outer wall. One end of the cylindrical body is provided with a plurality of recessed areas. The outer wall of the plurality of recessed areas forms a shape that matches the shape of the natural leaflets when open or closed. The outer wall of the cylindrical body is provided with a reference line, which provides a reference for aligning the stent and the support member. The clamping mold also includes a fixing member that is mounted on the exterior of the support member. The fixing member includes a base and a plurality of protrusions uniformly arranged on the base. The base is a circular ring. The protrusions are formed to protrude outward along the central axis of the base. Together, the protrusions form a "petal-shaped" structure. The edges of the protrusions away from the base form a positioning line. When the fixing member is mounted on the exterior of the support member, the reference line and the positioning line coincide. The clamping mold is made of metal, a hard polymer material, or a soft polymer material.

[0013] Furthermore, the polymer artificial heart valve prepared by the preparation method comprises:

[0014] A support; a skirt disposed on the support; and a leaflet having an edge bonded to an edge of the skirt. The skirt is made of one or more of polyethylene terephthalate, polyurethane, and a polyolefin-polyethylene terephthalate blended fabric. The leaflet is manufactured by a one-step process or a two-step process.

[0015] The one-step method comprises the following steps: forming a polymer film on the surface of the fabric in one step to produce a leaflet;

[0016] The two-step method comprises the following steps:

[0017] The fabric is immersed in a polymer C solution to obtain a fabric with impregnation layers on both sides; after the fabric with the impregnation layer is immersed in a poor solvent, it is laid flat on a substrate coated with a polymer D solution, so that the impregnation layer contacts the polymer D solution, and a coating layer is formed on the surface of one of the impregnation layers to obtain a leaflet; the contact surface of the impregnation layer and the coating layer are interlocked. The leaflet obtained by the two-step method includes: a fabric; two impregnation layers, which are respectively located on both sides of the fabric; at least one coating layer, which is located on the surface of the impregnation layer, and the contact surface of the impregnation layer and the coating layer are interlocked, and the surface roughness of the coating layer on the side away from the impregnation layer is 80-150nm. The thickness of the impregnation layer does not exceed 10μm, and the contact time of the fabric in the polymer C solution is 0.5-30min. The coating thickness of the polymer D solution is 100-1000μm. BRIEF DESCRIPTION OF THE DRAWINGS

[0018] FIG1 is a schematic diagram of the structural composition of a clamping mold and its positional relationship with a stent during the preparation of a polymer artificial heart valve in Example 1 of the present invention;

[0019] FIG2 is a schematic structural diagram of a support member for clamping the mold in FIG1 at one angle;

[0020] FIG3 is a schematic structural diagram of the support member for clamping the mold in FIG2 from another angle;

[0021] FIG4 is a schematic structural diagram of a fixing member for clamping the mold in FIG1 ;

[0022] The reference numerals are as follows:

[0023] Support member; 101, reference line; 20, bracket; 30, fixing member; 31, base; 32, bump. DETAILED DESCRIPTION

[0024] In order to make the purpose, technical solutions and advantages of this article clearer, this article is described in detail below with reference to the accompanying drawings and specific embodiments.

[0025] It should also be noted here that in order to avoid obscuring this article due to unnecessary details, the accompanying drawings only show structures and / or processing steps that are closely related to the solutions of this article, while other details that are not very relevant to this article are omitted.

[0026] In addition, it should be noted that the terms "comprises", "includes" or any other variations thereof are intended to cover non-exclusive inclusion, so that a process, method, article or apparatus that includes a series of elements includes not only those elements, but also includes other elements not explicitly listed, or also includes elements inherent to such process, method, article or apparatus.

[0027] The preparation method of the polymer artificial heart valve provided by the present invention has the following specific preparation process:

[0028] After preparing the skirt on the stent 20, a portion of the leaflet is placed on the surface of at least a portion of the skirt or the edge of the leaflet is docked with at least a portion of the skirt, and then the edge of the leaflet and the skirt are bonded together using interface micro-processing. After drying, an artificial heart valve is obtained.

[0029] When a portion of the leaflet is placed on the surface of at least a portion of the skirt, the leaflet and the skirt will contact each other. The interface micro-processing method can be achieved by bonding the edges of the leaflet and the skirt with the help of polymer B solution or by using thermal bonding between the leaflet and the skirt.

[0030] Herein, "joining" means that the edge of the leaflet and at least a portion of the skirt are aligned with each other but not in contact with each other. In this case, the interface micro-processing method is to bond the edges of the leaflet and the skirt with the help of polymer B solution.

[0031] In some embodiments, interface micro-processing can be achieved by bonding the leaflets and skirt edges together using a polymer B solution or by thermal bonding between the leaflets and skirt. The polymer B solution can be a polyurethane solution in N,N-dimethylacetamide or a SIBS solution in cyclohexane. The concentration of the polyurethane solution in N,N-dimethylacetamide is 10-20%, and the concentration of the SIBS solution in cyclohexane is 10-20%. The leaflets and skirt are bonded together using this method. The appropriate polymer B solution can be selected based on the materials of the skirt and leaflets, allowing for the production of artificial heart valves that meet the requirements of various usage environments.

[0032] In some embodiments, a method for preparing a skirt on a bracket 20 includes directly forming a skirt integrally connected to the bracket by dipping, specifically comprising the following steps: immersing the bracket 20 in a 10-20% by mass polyurethane dimethylacetamide solution, dipping and pulling at a pulling speed of 1000-1200 mm / s, drying at 50-60°C for 4-5 hours, and then dipping again at a pulling speed of 1000-1200 mm / s. After dipping, the bracket 20 is dried at 50-60°C for 48-60 hours, thereby forming a skirt on the bracket 20. The bracket 20 has a plurality of grids, which can be diamond-shaped or other shapes. The grids can be configured as needed in specific applications and are not limited thereto.

[0033] In particular, in some embodiments, the method of preparing the skirt on the bracket can also be to prepare the skirt in advance and then fix the skirt on the bracket 20. The fixing methods include sewing, gluing, etc. The specific fixing method can be selected according to needs, as long as the skirt can be fixed on the bracket 20, and this is not limited here.

[0034] In some embodiments, the solute of the polymer A solution used to prepare the skirt is a polymer such as polyethylene terephthalate (PET) and polyurethane (PU); in some embodiments, the skirt can also be a polyolefin-polyethylene terephthalate blended fabric (PO-PET) or a fabric of other polymer mixtures.

[0035] In some embodiments, the method of bonding the leaflet and the skirt together using polymer B solution is one or more of solution dipping, solution dispensing, and solution spraying, and the thermal bonding method is one or more of thermal welding, laser welding, and infrared welding. The width of the bonding area between the leaflet and the skirt is 1000-1200 μm. Those skilled in the art should understand that the width of the bonding area here is the bonding width between the leaflet and the skirt after the bonding operation is completed. This is because part of the polymer A solution will flow during the bonding process, or due to repeated bonding operations, the bonding area between the leaflet and the skirt is larger than the area when the polymer A solution and the skirt or leaflet first contact. When the leaflet and skirt are bonded by solution dipping and solution dispensing, the viscosity of the polymer B solution is 300-30,000 centipoise, the solid content of the solution is 5-30%, and the pulling speed during the dipping process is 1-10,000 μm / s. In a specific embodiment, the viscosity is 5,000-20,000 centipoise, the solid content of the solution is 10-20%, and the pulling speed is 500-2,000 μm / s. When the solution dispensing method is used, the glue discharge pressure is 40-60psi, and when the solution dipping method is used, the dipping and pulling speed is 1000-1200μm / s. It should be noted that during the bonding process, the same process can be repeated multiple times to ensure that when the leaflets and skirts are bonded together using polymer B solutions of different concentrations / viscosities, the bonding thickness is roughly the same, ensuring that the final valve strength is consistent. For polymer B solutions containing volatile solvents, they should all be dried before proceeding to the next step. Similarly, for non-solvent polymer B solution systems such as light curing and UV curing, the polymer liquid should be basically cured before proceeding to the next step.

[0036] When using a solution spraying method, the viscosity of the polymer B solution is 1-100 centipoise, and the solids content of the solution is 1-20%. In a specific embodiment, the viscosity is 5-50 centipoise, and the solids content of the solution is 3-8%. It should be noted that multiple spraying operations can be performed during the bonding process. For solvent-volatile polymer B solution systems, each spraying operation must ensure that the solution is substantially dry before the next spraying operation. For non-solvent polymer B solution systems such as those using light-curing or UV-curing methods, each spraying operation must ensure that the polymer liquid is solidified before proceeding to the next step. The spraying process can be operated manually with a handheld device or using a spray platform equipped with a visual recognition system.

[0037] In some embodiments, the material of the leaflet includes but is not limited to one or more of polyurethane (PU) and its fiber-reinforced materials, styrene-isobutylene-styrene copolymer (SIBS) and its cross-linked products, styrene-butadiene-styrene copolymer (SEBS) and its cross-linked products, silicone rubber (Q), and polytetrafluoroethylene (PTFE).

[0038] Furthermore, the leaflets used to prepare polymer prosthetic heart valves are produced using a one-step or two-step process. The one-step process includes the following steps: forming a polymer solution layer on the surface of a fabric, and then, after drying, forming a polymer film on the fabric surface, thereby producing a fiber-reinforced material that can be used as a leaflet. In particular, in some embodiments, the fabric is preferably a PET fabric, and the polymer solution is preferably a polyurethane solution; methods for forming the polymer solution layer include, but are not limited to, dipping and coating.

[0039] The two-step method includes the following steps:

[0040] The fabric is immersed in the polymer C solution and after the first drying, a fabric with impregnation layers on both sides is prepared;

[0041] Coating a polymer D solution on the substrate surface;

[0042] After immersing the fabric with the impregnated layer in a poor solvent, the fabric is laid flat on a substrate so that the impregnated layer contacts the polymer D solution. The fabric is then dried a second time to form a coating layer on the surface of one impregnated layer. The surface of the coating layer on the side away from the impregnated layer is smooth. During the drying process, under the action of the poor solvent, the contact surfaces of the impregnated layer and the coating layer become interlocked, thereby producing a leaflet (the leaflet in this step corresponds to the "polymer artificial heart valve composite material" in application number 2023117984628). It should be noted that in other embodiments, the above method can also be used to prepare a coating layer on the surface of another impregnated layer. That is, the number of coating layers in the composite material can be selected as needed.

[0043] In particular, the leaflet is produced using a two-step process, comprising:

[0044] fabric;

[0045] two impregnated layers, one on each side of the fabric;

[0046] At least one coating layer is located on the surface of the impregnation layer, and the contact surfaces of the impregnation layer and the coating layer are embedded in each other. The surface roughness of the coating layer on the side away from the impregnation layer is 80-150nm.

[0047] In some embodiments, 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.

[0048] In some embodiments, before immersing the fabric in a poor solvent, the fabric needs to be subjected to plasma treatment. The fabric treated in this way is more conducive to the poor solvent entering the interior of the fabric; wherein, the conditions of the plasma treatment are a processing power of 50-300W, a processing time of 30-300s, and a gas environment including but not limited to one of oxygen, hydrogen, air, argon, and helium.

[0049] In some embodiments, the polymer C solution is obtained by dissolving a first polymer in a first organic solvent, the mass concentration of the polymer C solution is 1-15 w / v%, and the contact time of the fabric in the polymer C solution is 0.5-30 min; the first polymer is one or more of polyurethane, polycarbonate-polyurethane copolymer, polysiloxane-polyurethane copolymer, and styrene / isobutylene 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.

[0050] In some embodiments, the first drying is performed at a temperature of 40-80° C. and for a time of 1-120 min.

[0051] In some embodiments, the polymer D solution is obtained by dissolving a second polymer in a second organic solvent, with the mass volume fraction of the polymer D solution being 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 with the same or similar properties as the impregnated layer to form the polymer D solution, the impregnated layer and the polymer D solution have better compatibility, facilitate the formation of an interlocking structure between the two, and enhance the stability within the coating and between the coating and the fabric.

[0052] In some embodiments, the second drying is performed at a temperature of 40-80° C. for a time of 6-48 hours.

[0053] In some embodiments, the thickness of the impregnation layer is less than 10 μm, and the coating thickness of the polymer D solution is 100-1000 μm. By controlling the above conditions, the coating thickness on the fabric surface can be regulated to minimize the impact of the coating on the softness of the fabric itself.

[0054] In some embodiments, methods of coating the polymer D solution include, but are not limited to, knife coating, spin coating, roller coating, and flow coating.

[0055] In some embodiments, the poor solvent includes but is not limited to water, alcohols, and ketones, such as ethanol, isopropanol, and acetone. Both the first polymer and the second polymer are not easily soluble in the poor solvent.

[0056] In some embodiments, the material of the substrate includes but is not limited to glass, metal, and silicone.

[0057] The process of bonding the leaflets to the skirt is accomplished with the aid of a clamping mold, which includes a support member 10 for supporting a stent 20. Specifically, the support member 10 is a cylindrical body with a smooth outer wall, whose structure is adapted to the stent 20, allowing the stent 20 to be sleeved onto the exterior of the support member 10. Multiple recessed areas are defined at one end of the cylindrical body. The outer walls of these recessed areas form a shape that matches the shape of the natural leaflets when open or closed, and the number of recessed areas matches the number of leaflets.

[0058] The clamping mold also includes a fixing part 30, which is sleeved on the outside of the support part 10. The fixing part 30 includes a base 31 and a plurality of protrusions 32 evenly arranged on the base 31, and the number of protrusions 32 matches the number of leaflets. The base 31 is a circular ring, and the protrusions 32 are formed by protruding outward along the central axis of the base 31. The edge lines of all protrusions 32 away from the base 31 together constitute a positioning line. The shape of the fixing part 30 is adapted to the structure of the skirt. When the support part 10 and the fixing part 30 are sleeved together, the positioning line coincides with the reference line 101. The material of the clamping mold is a metal material such as stainless steel, a hard polymer material such as polyformaldehyde, polyethylene, polytetrafluoroethylene, and a soft polymer material such as silicone rubber, natural rubber, and EPDM rubber.

[0059] In particular, a reference line 101 is provided on the outer wall of the support 10. The reference line 101 can provide a reference for aligning the stent 20 and the support 10 when the stent 20 is placed on the support 10. The reference line 101 can be used to identify whether the stent 20 is installed in the appropriate position on the support 10, ensuring that the edges of the leaflets and the skirt can be aligned after the leaflets are subsequently laid on the support. At the same time, when the fixing member 30 is placed on the support 10, the positioning line and the reference line 101 coincide with each other. At this time, the degree of overlap between the two can be used to confirm whether the edges of the skirt and the leaflets are aligned, further improving the accuracy of the bonding. In this way, when the leaflets and the skirt are bonded together, not only can the support 10 and the fixing member 30 be used to fix the two, but the fixing member 30 can also be used to protect the skirt from being dissolved and damaged by the polymer B solution, so as to facilitate the precise bonding of the leaflets and the skirt.

[0060] The polymer artificial heart valve and its preparation method are further described below with reference to specific examples:

[0061] Example 1

[0062] In this embodiment, a polymer artificial heart valve is prepared by bonding the leaflets and skirt together using a polyurethane / dimethylacetamide solution containing 20% ​​by mass of polyurethane. The model of the dipping and pulling machine used in the preparation process is SYDC-100, and the brand is Shanghai Sanyan. The bonding process is achieved with the aid of the clamping mold shown in Figures 1 to 4.

[0063] Specifically, the material of the above-mentioned clamping mold is stainless steel, and specifically includes a support member 10 and a fixing member 30 mounted on the outside of the support member 10; specifically, the support member 10 is a cylinder with a smooth outer wall, and its structure is adapted to the bracket 20 so that the bracket 20 can be mounted on the outside of the support member 10. Three recessed areas are provided at one end of the cylinder, and the shape formed by the outer walls of the three recessed areas is adapted to the shape of the natural leaflet when it is open or closed; the fixing member 30 includes a base 31 and three protrusions 32 evenly arranged on the base 31. The base 31 is a circular ring, and the protrusions 32 are formed by protruding outward along the central axis of the base 31. The structure of the protrusions 32 is shown in Figure 4. All the protrusions 32 together constitute a "petal-type" structure, and all the protrusions 32 away from the edge line of the base 31 together constitute a positioning line. Furthermore, a reference line 101 is provided on the outer wall of the support member 10. The reference line 101 is the edge line of each recessed area. The provision of the reference line 101 can provide a reference for the alignment of the support member 20 and the support member 10 when the support member 20 is mounted on the support member 10. The reference line 101 is used to identify whether the support member 20 is installed in the appropriate position of the support member 10, which is beneficial for aligning the edges of the leaflets and the skirt when the leaflets are subsequently laid on the support member 10. At the same time, when the fixing member 30 is mounted on the support member 10, the positioning line and the reference line 101 coincide with each other. At this time, the edges of the skirt and the leaflets are aligned, ensuring the accuracy of the bonding process. It should be noted that in other embodiments, the protrusion 32 can also be of other shapes, and the position of the reference line can also be adjusted as needed, as long as the leaflets can be fixed to the skirt surface on the support member. This is not limited to this.

[0064] The specific preparation method of the polymer artificial heart valve is as follows:

[0065] S1. Evenly apply a 16% polyurethane solution on the surface of the PET fabric, and after drying, laser cut the polyurethane fiber-reinforced leaflets. The leaflets are 100 microns thick and are sized to accommodate the size of the stent 20. It should be noted that in other embodiments, a two-step method can also be used to prepare the leaflets.

[0066] The stent 20 is dipped twice in a 20% by mass polyurethane / N,N-dimethylacetamide solution at a temperature of 25° C. and a pulling speed of 1000 mm / s. After one dipping, the stent is dried at 50° C. for 4 hours before the next dipping step is performed. After the second dipping step, the stent is dried at 50° C. for 48 hours to obtain a stent 20 coated with a skirt. After two dipping steps, the skirt composed of the polyurethane film can be evenly coated on the stent 20. The film thickness on the metal rod of the stent 20 can reach about 50 μm, and the film thickness between the rhombus grids of the stent 20 can reach about 100 μm, which can ensure that the skirt remains intact during use in the valve delivery device and in the human body. The stent 20 has a plurality of rhombus grids, each having a base diameter of 3.1 cm and a height of 3.6 cm.

[0067] S2. Adhere the leaflet and the skirt together by dispensing solution. The specific process is as follows: After the stent 20 covered with the skirt is placed on the support 10, the edge of the leaflet is laid on the surface of the skirt so that a part of the leaflet overlaps the skirt. The leaflet is aligned according to the reference line 101 on the surface of the support 10 so that the areas to be bonded of the leaflet and the skirt are aligned with each other. Then, the fixing member 30 is placed on the outside of the support 10. The skirt and the leaflet are fixed by a clamping mold. This can prevent the polyurethane skirt from being dissolved and damaged by the polymer solution used subsequently in subsequent operations. Then, in the continuous dispensing mode of the manual dispensing machine, the areas to be bonded of the leaflet and the skirt were bonded together using a polyurethane N,N-dimethylacetamide solution, and the width of the bonding area between the two was 1000 μm. The dispensing pressure during the dispensing process was 50 psi, and the needle moved slowly along the edge line of the leaflet during dispensing so that the areas to be bonded of the leaflet and the skirt could all be exposed to the polyurethane dimethylacetamide solution. After the dispensing was completed, the product was dried at 50°C for 4 hours. Then, the above dispensing process was repeated, and the product was dried at 50°C for 48 hours to obtain a polymer artificial heart valve.

[0068] Example 2

[0069] This embodiment prepares a polymer artificial heart valve. The dispensing machine used in this embodiment is of the brand Nordson. The structures of the clamping mold and the stent 20 used are the same as those in Example 1 and will not be repeated here. The specific preparation method includes the following steps:

[0070] S1. Pour 5 g of a 12.5% ​​by mass polyurethane dimethylacetamide solution into a 10 cm diameter Petri dish, spread evenly, and dry at 50°C for 48 hours. After film formation, laser cutting is performed to obtain a three-piece integral leaflet with a thickness of 90 μm. It should be noted that in other embodiments, a two-step method can also be used to prepare the leaflet.

[0071] The stent 20 is immersed twice in a dimethylacetamide solution of 20% by mass polyurethane, with the immersion parameters being 25° C. and the pulling speed being 1000 mm / s. After the first immersion, the stent is dried in a 50° C. environment for 4 hours, and then the above steps are repeated for a second immersion. After the immersion is completed, the stent is dried in a 50° C. environment for 48 hours to obtain a stent 20 coated with a skirt. After the two immersion processes, the skirt can be evenly coated on the stent 20. The film thickness on the metal rod of the stent 20 can reach about 50 μm, and the film thickness between the diamond grids of the stent 20 can reach about 100 μm, which can ensure that the skirt remains intact during the use of the valve delivery device and in the human body;

[0072] S2. Use solution dispensing to bond the leaflet and the skirt together. The specific process is as follows: After the bracket 20 covered with the skirt is placed on the support 10, the leaflet is laid on the support 10, and the leaflet is aligned according to the reference line 101 on the surface of the support 10 so that the edge of the leaflet is docked with the skirt, that is, the areas to be bonded of the leaflet and the skirt are aligned with each other under the support of the support 10 but do not contact each other, and then the fixing part 30 is placed on the outside of the support 10, and the skirt and the leaflet are fixed with a clamping mold, while avoiding the polymer solution used when the polyurethane skirt is bonded in subsequent operations. Liquid dissolution damage; then, a glue sprayer with a visual recognition system is used to identify and determine the glue dispensing path, and then the polymer B solution (18% by mass of polyurethane N,N-dimethylacetamide solution) is used to bond the leaflet and the skirt together. The width of the bonding area between the two is 1200μm, of which the glue dispensing path width is 1000μm. During glue dispensing, the edges of the leaflet and the skirt can all contact with the polymer B solution. After one glue dispensing is completed, it is heated at 50℃ for 4h, and then the above glue dispensing process is repeated. Then, it is dried at 50℃ for 48h to obtain a polymer artificial heart valve.

[0073] Example 3

[0074] This embodiment prepares a polymer artificial heart valve. The structures of the clamping mold and the stent 20 used are the same as those in Example 1 and will not be repeated here. The specific preparation method includes the following steps:

[0075] S1. Pour 5 g of a 20% by mass SIBS / cyclohexane solution into a 10 cm diameter Petri dish, spread evenly, and dry at 50°C for 48 h. After film formation, laser cutting is performed to obtain a three-piece integral leaflet with a thickness of 140 μm; the skirt is made of PET fabric. It should be noted that in other embodiments, the leaflet can also be prepared using a two-step process.

[0076] S2. Use PTFE sutures to sew the skirt directly onto the bracket 20, with the edge of the sewing position attached to the edge of the leaflet; place the leaflet on the surface of the skirt, and then cover the inside and outside of the leaflet with a layer of room temperature curing silicone sealant, and leave it at room temperature for 2 hours to allow the sealant to dry, and then perform the bonding operation. The specific bonding process is as follows: After the bracket 20 with the skirt is placed on the support 10, the edge of the leaflet is laid on the surface of the skirt so that a part of the leaflet overlaps with the skirt, and the leaflet is aligned according to the reference line 101 on the surface of the support 10 so that the leaflet and the skirt to be bonded are aligned with each other, and then fixed. Part 30 is sleeved on the outside of the support part 10, and the skirt and leaflets are fixed by a clamping mold, while preventing the polyurethane skirt from being dissolved and damaged by the polymer solution used for bonding in subsequent operations; then, the clamping mold with the leaflets and skirt fixed is immersed as a whole in a 20% by mass SIBS / cyclohexane solution, and the immersion and pulling speed is 1000μm / s. After the immersion is completed, it is at a temperature of 50℃ for 4h, and then the above immersion process is repeated. It is then dried at 50℃ for 48h to obtain a polymer artificial heart valve. The width of the bonding area between the leaflets and the skirt in the valve is 1000μm.

[0077] Example 4

[0078] This embodiment prepares a polymer artificial heart valve. The structure of the clamping mold used is different from that of Example 1 except for the support member 10. The structure of the support member 10 is basically the same as that of Example 1 and will not be described in detail here. The specific preparation method includes the following steps:

[0079] S1. A polyurethane solution with a concentration of 16% is evenly scraped onto the surface of the PET fabric, and after drying, it is laser cut to obtain a polyurethane fiber-reinforced leaflet with a thickness of 90 microns. It should be noted that in other embodiments, a two-step method can also be used to prepare the leaflet; the stent 20 is immersed twice in a 20% by mass polyurethane / N,N-dimethylacetamide solution, and the immersion parameters are immersion and pulling at a pulling speed of 1000 mm / s at 25°C. After one immersion, it is dried at 50°C for 4 hours, and then the next immersion process is carried out; after the second immersion is completed, it is dried at 50°C for 48 hours to obtain a stent 20 covered with a skirt; after two immersion processes, a uniform polyurethane film is formed on the surface of the stent 20, and the film thickness on the stent 20 can reach about 50 μm, and the film thickness between the rhombus grids of the stent 20 can reach about 100 μm, which can ensure that the skirt remains intact during the valve delivery device and use in the human body;

[0080] S2. Use heat welding to bond the leaflet and the skirt together. Dry the leaflet at 100°C for 6 hours before welding. The specific process is as follows: After the bracket 20 covered with the skirt is placed on the support 10, the edge of the leaflet is laid on the surface of the skirt so that a part of the leaflet overlaps the skirt, and the leaflet is aligned according to the reference line 101 on the surface of the support 10 so that the areas to be bonded of the leaflet and the skirt are aligned with each other, and then a soldering iron with a top width of 1mm is attached to the connection between the leaflet and the skirt to melt the polyurethane on the leaflet, and the molten polyurethane is used to bond the leaflet and the skirt together. During the welding process, the temperature of the soldering iron is 180°C, and the moving speed of the soldering iron is 10mm / s. After welding is completed, annealing is carried out in a constant temperature blast drying oven at 85°C for 4 hours. Then the oven is slowly cooled to room temperature, and the valve is taken out. The width of the bonding area between the leaflet and the skirt in the valve is 1000μm.

[0081] The valve performance of Examples 1 to 4 is shown in Table 1. The evaluation of valve performance is based on the industry standard (YY / T 1449.3-2016 Transcatheter Implantable Artificial Heart Valve). As can be seen from the data in Table 1, the fatigue times of the valves prepared in Examples 1 to 4 all exceeded 400 million times, and none of them failed at the end of the test. The remaining performance characteristics all met the minimum performance requirements of the industry standard.

[0082] Table 1 Comparison of valve performance obtained in Examples 1 to 4

[0083]

[0084] The above embodiments are only used to illustrate the technical solutions of this article and are not intended to limit them. Although this article has been described in detail with reference to the preferred embodiments, those skilled in the art should understand that the technical solutions of this article may be modified or replaced by equivalents without departing from the spirit and scope of the technical solutions of this article.

Claims

1. A method for preparing a polymer artificial heart valve, characterized in that: The following steps are involved: Preparing a skirt on the bracket; Placing a portion of the leaflet on the surface of at least a portion of the skirt or making the edge of the leaflet butt against at least a portion of the skirt, wherein both the leaflet and the skirt are made of polymer materials; Adhere the edges of the leaflet and the skirt together by interface micro-processing, and obtain the polymer artificial heart valve after drying; The interface micro-processing is achieved by bonding the edges of the leaflet and the skirt with the aid of a polymer B solution or by utilizing thermal bonding between the leaflet and the skirt. The polymer B solution has a viscosity of 300-300000 centipoise and a solid content of 5-30%.

2. The preparation method according to claim 1, characterized in that: The method for preparing the skirt on the bracket includes directly forming the skirt integrally connected with the bracket on the bracket by a dipping method or fixing the pre-made skirt on the bracket.

3. The preparation method according to claim 2, characterized in that: The method for preparing the skirt by dipping comprises the following steps: immersing the bracket in a polymer A solution with a mass percentage of 10-20%, dipping and pulling at a pulling speed of 1000-1200 mm / s, and drying at 50-60°C for 4-5 hours, and then dipping for the second time at a pulling speed of 1000-1200 mm / s. After the dipping is completed, the skirt is dried at 50-60°C for 48-60 hours to obtain the skirt on the surface of the bracket.

4. The preparation method according to claim 1, characterized in that: The method of bonding the leaflet and the skirt together using the polymer B solution is one or more of a solution dipping method, a solution dispensing method, and a solution spraying method; the thermal bonding method is one or more of a thermal welding method, a laser welding method, and an infrared welding method; the width of the bonding area between the leaflet and the skirt is 1000-1200 μm.

5. The preparation method according to claim 4, characterized in that: When the leaflet and the skirt are bonded by the solution dipping method, the pulling speed during the dipping process is 1-10000 μm / s.

6. The preparation method according to claim 4, characterized in that: When the solution dispensing method is adopted, the dispensing pressure is 40-60 psi; when the solution spraying method is adopted, the viscosity of the polymer B solution is 1-100 centipoise, and the solid content of the solution is 1-20%.

7. The preparation method according to claim 1, characterized in that: The process of bonding the leaflet and the skirt is carried out with the aid of a clamping mold, which includes a support member for supporting the bracket; the support member includes a cylinder with a smooth outer wall, one end of the cylinder is provided with a plurality of recessed areas, the shape formed by the outer walls of the plurality of recessed areas is adapted to the shape of the natural leaflet when it is in an open or closed state, and the outer wall of the cylinder is provided with a reference line, which is used to provide a reference for the alignment of the bracket and the support member.

8. The preparation method according to claim 7, characterized in that: The clamping mold also includes a fixing part, which is sleeved on the outside of the support part; the fixing part includes a base and a plurality of protrusions evenly arranged on the base, the base is a circular ring, and the protrusions are formed by protruding outward along the central axis direction of the base, and all the protrusions together constitute a "petal-shaped" structure; the edge lines of all the protrusions away from the base together constitute a positioning line; when the fixing part is sleeved on the outside of the support part, the reference line and the positioning line coincide.

9. The preparation method according to claim 8, characterized in that: The clamping mold is made of metal material, hard polymer material or soft polymer material.

10. A polymer artificial heart valve, characterized in that: The polymer artificial heart valve is prepared by the preparation method according to any one of claims 1 to 9, which comprises: Bracket; A skirt, which is arranged on the bracket; The edges of the petals are bonded to the edges of the skirt.

11. The polymer artificial heart valve according to claim 10, characterized in that: The skirt is made of one or more of polyethylene terephthalate, polyurethane, and polyolefin-polyethylene terephthalate blended fabric.

12. The polymer artificial heart valve according to claim 10, characterized in that: The leaflet is prepared by a one-step method or a two-step method; The one-step method comprises the following steps: forming a polymer film on the surface of the fabric in one step to obtain a leaflet; The two-step method comprises the following steps: The fabric is immersed in the polymer C solution to prepare a fabric having an impregnation layer on both sides; After immersing the fabric with the impregnation layer in a poor solvent, the fabric is laid flat on a substrate with a polymer D solution coated on the surface, so that the impregnation layer is in contact with the polymer D solution, and a coating layer is formed on the surface of one of the impregnation layers to obtain a leaflet; The contact surfaces of the impregnation layer and the coating layer are interlocked.

13. The polymer artificial heart valve according to claim 12, characterized in that: The valve leaflet prepared by the two-step method comprises: Fabric; two impregnation layers, which are respectively located on both sides of the fabric; At least one coating layer is located on the surface of the impregnation layer, and the contact surfaces of the impregnation layer and the coating layer are interlocked, and the surface roughness of the coating layer on the side away from the impregnation layer is 80-150nm.

14. The polymer artificial heart valve according to claim 12, characterized in that: The thickness of the impregnation layer does not exceed 10 μm, and the contact time of the fabric in the polymer C solution is 0.5-30 minutes.

15. The polymer artificial heart valve according to claim 12, characterized in that: The coating thickness of the polymer D solution is 100-1000 μm.

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