Implantable material, artificial prosthesis, artificial heart valve, valve leaflet prefabricated product and preparation method

Abstract

The invention discloses an implantable material, an artificial prosthesis, an artificial heart valve and a preparation method, and the preparation method of the implantable material comprises the following steps: S100, providing a polymeric membrane; step S200, carrying out swelling treatment on the polymeric membrane; and step S300, keeping the polymeric membrane in a predetermined three-dimensional shape and carrying out drying treatment to obtain the implantable material. Swelling treatment is carried out on the polymeric membrane in a three-dimensional shape, molecular chain segment movement in the membrane can be increased, and secondary shaping can be carried out under the condition that no internal stress exists, so that stress distribution of materials is improved, the deformation quantity in the valve movement period is reduced, meanwhile, the uniformity of the thickness of the membrane is considered, and degradation caused by high temperature is reduced.

Description

Implantable material, artificial prosthesis, artificial heart valve, leaflet preform and preparation method Technical Field

[0001] The present application relates to the field of artificial valve technology, and in particular to implantable materials, artificial prostheses, artificial heart valves, leaflet prefabricated products, and preparation methods. Background Art

[0002] Polymer materials are increasingly being used as prosthetic materials in artificial prostheses. Taking heart valves as an example, polymer materials can be applied to parts such as the leaflets or skirts. However, although such implantable polymer material devices have good biocompatibility, they face the problem of insufficient fatigue performance. For example, the polymer leaflets are prone to tearing at the center of the free edge with large deformation or at the connection with the stent.

[0003] Some existing technologies use stereolithography to prepare devices and optimize the stress and strain of materials. Two commonly used methods include dip coating on the mold surface and hot pressing in the mold cavity.

[0004] Dip coating involves applying a polymer solution to the three-dimensional mold surface. As the polymer solution evaporates, it solidifies on the mold surface, forming a three-dimensional polymer membrane. However, due to the three-dimensional mold shape, gravity causes the polymer solution to flow on the mold surface, making it difficult to control the thickness of the membrane at different locations. This ultimately affects the uniformity and consistency of the membrane, and consequently, the fatigue performance and yield rate of the valve.

[0005] Hot-press molding involves forming a three-dimensional diaphragm by melting a polymer within the cavities of a male and female mold. This method typically requires heating the polymer to temperatures above 190°C. At high temperatures, the polymer degrades to varying degrees, reducing its molecular weight and even producing toxic small molecules. This, in turn, affects the valve's biological, mechanical, and aging properties. Technical Solutions

[0006] The present application provides a method for preparing an implantable material, comprising the following steps:

[0007] Step S100, providing a polymer film;

[0008] Step S200, performing swelling treatment on the polymer film;

[0009] Step S300 , maintaining the polymer film in a predetermined three-dimensional shape and performing a drying process to obtain the implantable material.

[0010] The implantable material can be applied to an artificial heart valve, that is, the present application provides a method for preparing an artificial heart valve material.

[0011] Optionally, the method for preparing the polymer film includes:

[0012] Dissolving the raw material in a first solvent to prepare a solution with a mass percent concentration of 3% to 40%;

[0013] forming a film on the surface of the mold using the solution;

[0014] The polymer film is then obtained by drying.

[0015] Optionally, the raw material is at least one of polyurethane, polyolefin, polysiloxane, polyvinyl alcohol, and Pebax.

[0016] Optionally, the first solvent is selected from a good solvent for the raw material, for example, at least one selected from DMAc, DMF, tetrahydrofuran, DMSO, toluene, cyclohexane, xylene, and dichloromethane.

[0017] Optionally, the drying temperature is 25-80° C. The drying time is 1-48 hours, for example, 6-24 hours.

[0018] Optionally, inert gas protection is used during the drying.

[0019] Optionally, the thickness of the polymer film is 0.1-0.6 mm, preferably 0.1-0.3 mm.

[0020] Optionally, the polymer membrane is a tubular structure, and each leaflet corresponds to a portion of a side wall of the tubular structure.

[0021] Optionally, the cylindrical structure is a prefabricated integral structure, and the swelling treatment and the drying treatment are performed under the cylindrical structure.

[0022] Optionally, the polymer film is prefabricated into a sheet structure, and then the sheet structure is rolled up so that two opposite sides are fixed to each other to form a cylindrical structure.

[0023] Optionally, the swelling treatment and drying treatment of the polymer film are carried out in a sheet-like structure, and then formed into a cylindrical structure after completion.

[0024] Optionally, the polymer film has a predetermined three-dimensional shape with a bending portion, and the swelling treatment is performed on at least the bending portion or on the entire polymer film.

[0025] Optionally, the polymer film is maintained in a predetermined three-dimensional shape when the polymer film is subjected to a swelling treatment; or the polymer film is maintained in a predetermined three-dimensional shape after the polymer film is subjected to a swelling treatment.

[0026] Optionally, before performing the swelling treatment on the polymer film, the polymer film is first mounted on a mold matching the predetermined three-dimensional shape, and then a treatment liquid for swelling is injected into the mold.

[0027] Optionally, during the swelling treatment, the treated area is immersed in a treatment liquid that is a poor solvent for the polymer film, such as a second solvent or an aqueous solution of the second solvent, wherein the second solvent is selected from at least one of ethanol, propanol, isopropanol, tetrahydrofuran, acetone, and toluene, and the total concentration of the second solvent in the aqueous solution is greater than or equal to 30% by mass.

[0028] Optionally, the polymer membrane is partially or entirely subjected to swelling treatment until the volume change rate of the treated portion is 0.1%-10%.

[0029] Optionally, the swelling treatment time is 0.1-24 hours, for example 0.1-12 hours.

[0030] Optionally, a mold is used to support at least one side of the polymer film to maintain a predetermined three-dimensional shape.

[0031] Optionally, the drying temperature is 25-80° C. and the drying time is 0.5-48 hours, for example, 1-16 hours.

[0032] Optionally, an inert gas atmosphere may be used during the drying process.

[0033] Optionally, during the drying process, the predetermined three-dimensional shape of the polymer film is always maintained, for example, the mold always supports the polymer film, or the predetermined three-dimensional shape of the polymer film is maintained only in a partial period of time.

[0034] Optionally, the drying process includes a relatively early stage and a late stage, and the predetermined three-dimensional shape of the polymer film is maintained at least in the early stage, wherein the early stage accounts for at least 15% of the entire drying process time.

[0035] Optionally, the leaflet has a relative open shape and a closed shape under the action of fluid, as well as a transition shape during the switching process, and the predetermined three-dimensional shape corresponds to the closed shape or the transition shape of the leaflet.

[0036] Optionally, the opening area corresponding to the leaflet in the artificial heart valve in the open shape is S1, and the opening area corresponding to the leaflet in the transition shape is S2, and the percentage of S2 to S1 is greater than 0 and less than or equal to 85%.

[0037] The present application also provides an implantable material and an artificial heart valve material, each of which uses a polymer film, and at least a portion of the polymer film is pre-shaped into a three-dimensional shape.

[0038] The implantable material and artificial heart valve material can be obtained by using the preparation method of the present application.

[0039] The present application also provides an artificial prosthesis and an artificial heart valve. At least a portion of the artificial prosthesis is made of the implantable material described above. The artificial heart valve comprises a stent and leaflets connected to the stent, wherein the leaflets are made of the artificial heart valve material described in the present application.

[0040] The present application also provides a method for preparing the artificial heart valve, wherein the artificial heart valve comprises a stent and a plurality of leaflets connected to the stent, and the method comprises:

[0041] Providing a polymer film for preparing a leaflet;

[0042] performing a swelling treatment on the polymer film;

[0043] Maintaining the polymer film in a predetermined three-dimensional shape and performing a drying process;

[0044] The dried polymer film is installed on the stent to obtain the artificial heart valve.

[0045] Optionally, before the dried polymer film is mounted as a leaflet on the stent, the polymer film is cut according to the contour shape of the leaflet in any step.

[0046] Optionally, the leaflet is mounted to the stent before the swelling treatment or after the drying treatment.

[0047] Optionally, multiple leaflets are prepared separately and then mounted on the stent.

[0048] Optionally, after the multiple leaflets are prepared separately, they are first connected end to end in sequence to form a cylindrical structure, and then installed on the bracket.

[0049] Optionally, the multiple leaflets form an integrated structure.

[0050] The present application also provides a method for preparing the artificial heart valve, wherein the artificial heart valve comprises a stent and a plurality of leaflets connected to the stent, and the method comprises:

[0051] providing a polymer film having a leaflet-shaped contour;

[0052] installing the polymer membrane on the bracket and performing a swelling treatment on the polymer membrane;

[0053] The artificial heart valve is obtained by maintaining the predetermined three-dimensional shape of the polymer film and performing a drying process together with the stent.

[0054] Optionally, the artificial heart valve further includes a covering connected to the stent, and the covering is made of the artificial heart valve material.

[0055] Optionally, the covering membrane and the leaflet are separately connected or are an integral structure.

[0056] Optionally, the stent is in a radially deformable cylindrical shape with a blood flow channel inside. The leaflets are located on the inner side of the stent to control the blood flow channel, and the covering is located on the blood flow inflow side of the leaflets.

[0057] Optionally, the coating is located on the radial inner side and / or outer side of the stent.

[0058] Optionally, the method further includes heat treating the artificial heart valve at a temperature of 80° C. to 160° C., using an inert gas shield, and for a time of 0.5 to 4 hours.

[0059] The present application also provides a leaflet preform of an artificial heart valve, wherein the leaflet preform is cylindrical and comprises a plurality of leaflets connected end to end in sequence. Beneficial effects

[0060] In this application, swelling the polymer film in a three-dimensional shape increases the movement of molecular segments within the film, allowing for secondary shaping without internal stress. This improves material stress distribution while maintaining uniform film thickness and minimizing degradation caused by high temperatures. BRIEF DESCRIPTION OF THE DRAWINGS

[0061] FIG1 is a flow chart of the preparation method of the implantable material of the present application;

[0062] 2 to 6 are schematic diagrams showing the principles of different implementations for preparing artificial heart valves. Modes for Carrying Out the Invention

[0063] The following will be combined with the drawings in the embodiments of this application to clearly and completely describe the technical solutions in the embodiments of this application. Obviously, the embodiments described are only part of the embodiments of this application, not all of the embodiments. Based on the embodiments in this application, all other embodiments obtained by ordinary technicians in this field without making creative efforts are within the scope of protection of this application.

[0064] It should be noted that when a component is referred to as being "connected" to another component, it may be directly connected to the other component or there may be an intermediate component. When a component is referred to as being "disposed on" another component, it may be directly disposed on the other component or there may be an intermediate component.

[0065] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by those skilled in the art to which this application pertains. The terms used herein in the specification of this application are for the purpose of describing specific embodiments only and are not intended to limit this application. The term "and / or" as used herein includes any and all combinations of one or more of the associated listed items.

[0066] Unless otherwise specified, solution concentrations mentioned below are by mass (weight) percentage. If no solvent is mentioned in a solution, the solvent is water. The artificial prosthesis and implantable materials in each embodiment are described using the field of artificial heart valves as an example, but are not strictly limited thereto. For example, the artificial prosthesis may be an artificial heart valve, and the implantable material may be the leaflets, skirt, or auxiliary materials of the artificial heart valve.

[0067] An embodiment of the present application provides a method for preparing an implantable material. The implantable material can be specifically applied to an artificial heart valve, that is, a method for preparing an artificial heart valve material is also provided.

[0068] Referring to Figure 1, the preparation method includes the following steps:

[0069] Step S100, providing a polymer film;

[0070] Step S200, performing swelling treatment on the polymer film;

[0071] In step S300 , the polymer film is maintained in a predetermined three-dimensional shape and dried to obtain an implantable material.

[0072] The polymer membrane in step S100 can be made of biocompatible polymer materials in conventional technology. In combination with the characteristics of artificial heart valves that require long-term periodic movement, this application uses at least one raw material selected from polyurethane, polyolefin, polysiloxane, polyvinyl alcohol, and Pebax. Its better elasticity is also particularly suitable for interventional implantation. During interventional delivery, artificial prostheses generally require radial compression, and the relative deformation position between the polymer material and the stent generates internal stress of traction or even deformation. Better elasticity can absorb stress and reduce the risk of local damage.

[0073] One embodiment of the present application also provides a method for preparing a polymer film, including:

[0074] Dissolving the raw material in a first solvent to prepare a solution with a mass percent concentration of 3% to 40%;

[0075] The solution is evaporated on the mold surface to form a film, which is then dried to obtain a polymer film.

[0076] The first solvent is a good solvent for the raw material. For polyurethane, for example, the first solvent is selected from at least one of DMAc, DMF, DMSO, tetrahydrofuran, toluene, cyclohexane, xylene, and dichloromethane. Depending on the subsequent application, the molding surface provided by the mold can be flat or curved. When using a curved surface, a regular shape such as a cylinder is preferred to ensure uniform thickness, particularly the inner or outer surface of a rotating body. The mold can be rotated during film formation to overcome uneven thickness caused by gravity.

[0077] Application to the mold surface can be achieved by spraying, brushing, pouring, or other methods. Drying conditions, for example, are at a temperature of 25-80°C. Drying time is 1-48 hours, for example, 6-24 hours. An inert gas blanket, such as nitrogen, can also be used during drying. Depending on the intended use of the implant material, the polymer film thickness can range from 0.1-0.6 mm, with a preferred thickness for applications in artificial heart valves being 0.1-0.3 mm.

[0078] In combination with the spatial characteristics of the leaflets in artificial heart valves or similar structures, the prepared polymer film has a cylindrical structure, and each leaflet corresponds to a part of the side wall of the cylindrical structure. Multiple leaflets can be formed at one time, which also reduces the workload of reconnecting the leaflets. The cylindrical structure can be a prefabricated integral structure, that is, formed using the surface of a rotating body mold. In the subsequent process, the cylindrical structure is subjected to swelling and drying treatment.

[0079] The polymer membrane can also be prefabricated into a sheet structure, i.e. a flat membrane. The subsequent swelling and drying processes are carried out in the sheet state. After completion, the sheet structure is curled so that the two opposite sides are fixed to each other to form a cylindrical structure, and then cut and installed on the bracket.

[0080] The polymer film provided in step S100 needs to be shaped according to a predetermined three-dimensional shape. There will be bending parts in the predetermined three-dimensional shape. The bending parts can be relatively smooth curved surfaces or folds with a more obvious trend. The swelling treatment is at least targeted at the bending parts. This does not mean that all bending parts need to be swelled. It can be implemented according to the expected performance requirements. For the convenience of operation, the entire polymer film and even the mold can be placed in the swelling system.

[0081] When the polymer film is subjected to swelling treatment, the polymer film can be maintained in a predetermined three-dimensional shape by using mold support or other means, and then swelling can be performed; it can also be performed first, that is, no three-dimensional shaping is performed during swelling, but after step S200, the polymer film is maintained in a predetermined three-dimensional shape and dried.

[0082] Before swelling the polymer membrane, the polymer membrane is first placed in a mold that matches the predetermined three-dimensional shape, and then the treatment liquid for swelling is injected into the mold. The mold can have a reserved injection hole, and the entire mold can also be immersed.

[0083] The polymer film after swelling treatment, or the polymer film together with the mold, is dried, that is, the solvent molecules in the polymer film system are removed, so that the entire polymer film, or at least the bending part, is in a state of uniform stress distribution, thereby improving the fatigue resistance of the bending part.

[0084] To address the problem of poor fatigue resistance of polymers, the present application performs three-dimensional shaping when there is no internal stress in the entire polymer film or at least in the bent parts. When applied to artificial heart valves, the stress distribution of the leaflets can be optimized and the maximum deformation of the leaflets can be reduced. The thickness of the leaflets is controllable, and there is no problem of high-temperature degradation during the preparation process, thereby improving the fatigue resistance of the valve.

[0085] Compared to existing dip-coating 3D molding, the product in this application boasts controllable thickness and no batch variability, significantly improving the yield rate of finished products. Compared to existing hot press molding, the pre-molding mold structure is simpler, and the process eliminates the need for high-temperature melting, preventing polymer degradation. This reduces biocompatibility risks and increases the lifespan of polymer materials.

[0086] During the swelling treatment, the part to be treated is soaked in a treatment liquid, which is the second solvent or an aqueous solution of the second solvent.

[0087] The second solvent is selected from at least one of ethanol, propanol, isopropanol, tetrahydrofuran, acetone, and toluene. When an aqueous solution of the second solvent is used, the total concentration of the second solvent in the aqueous solution is greater than or equal to 30% by mass, for example, 30% to 90%, or even 40% to 80%.

[0088] The polymer membrane is partially or entirely swollen until the volume change rate of the treated part is 0.1%-30%, such as 0.1-15%, and another example is 5-10%. The swelling time can also be more intuitively controlled, for example, the swelling treatment time is 0.1-24h, such as 0.1~12h, such as 1~10h, and another example is 2~8h.

[0089] In order to eliminate the stress at the bent part, the predetermined three-dimensional shape must be maintained during swelling, drying and shaping. For example, in one embodiment, a mold is used to support at least one side (thickness direction) of the polymer film, and the polymer film is adhered to the mold surface through gravity, clamps, etc. The mold can also be a snap-fit ​​structure, that is, it encloses a mold cavity and restricts both sides of the polymer film at the same time.

[0090] In order to facilitate the drying process after swelling is completed, the mold can be selected to be non-fully enclosed, for example, only one side of the polymer film is fully supported, and the other side is fixed at multiple points or edge clamped.

[0091] The drying temperature in step S300 is 25-80° C., for example, 40-60° C. The drying process may be carried out under an inert gas such as nitrogen, and the drying time is 0.5-48 hours, for example, 1-16 hours, or 2-6 hours.

[0092] During the drying process, the predetermined three-dimensional shape of the polymer film is always maintained, for example, the mold always supports the polymer film, or the predetermined three-dimensional shape of the polymer film is only maintained for part of the time period, that is, the mold supports the polymer film for part of the time period.

[0093] The support force that maintains the three-dimensional shape only for a part of the time period can be released during the drying process. For example, after the polymer film has been dried for a period of time, it can basically maintain the configuration. At this time, removing the mold can speed up the volatilization process of the residual volatiles and improve the overall efficiency. For example, the entire drying process includes a relatively early and late period. In one embodiment, the mold supports the polymer film at least in the early period, wherein the early period accounts for at least 15% of the entire drying process time, such as 20~60%. Taking the total drying time of 6 hours as an example, the polymer film is always bound and supported by the mold for the first 3 hours, and the polymer film and the mold are in a separated state for the next 3 hours. However, it is not strictly required that there is no support. The polymer film is still supported by hanging, flat placement, multi-point support, etc., but it is no longer in full-surface contact.

[0094] The predetermined three-dimensional shape must be implemented in conjunction with product design. For example, the leaflets, under the action of fluid, have relative open and closed shapes, as well as transitional shapes during the transition process. The predetermined three-dimensional shape corresponds to the closed or transitional shape of the leaflets. In one embodiment, a transitional shape is preferred, and its shape characteristics can be described by its opening area. For example, the opening area corresponding to the leaflet in the open shape of a prosthetic heart valve is S1, and the opening area corresponding to the leaflet in the transitional shape is S2. The percentage of S2 to S1 is greater than 0 and less than or equal to 85%. A value of 0 indicates a closed shape.

[0095] In the transitional shape, the leaflet's extreme bending angle is significantly reduced during the opening and closing cycle, whether it tends towards an open shape or a closed shape, which greatly reduces the deformation amount during the leaflet movement process, thereby increasing the number of bending times and extending the service life.

[0096] Based on the above preparation method, corresponding implantable materials can be obtained, specifically artificial heart valve materials. Regarding their application, they can be further processed to obtain artificial prostheses and artificial heart valves. At least a portion of the artificial prosthesis is made of the implantable material.

[0097] In addition to the polymer membrane as the main part, the implantable material of the present application may also contain partial or overall reinforcing fabric as needed. The reinforcing fabric can be directly embedded in the process of synthesizing the polymer membrane, or the film can be formed on the reinforcing fabric by dipping or other methods. At this time, the reinforcing fabric can also be understood as a mold to support the shape of the polymer membrane without affecting subsequent swelling or drying operations.

[0098] The following multiple embodiments take artificial heart valves as an example, especially artificial heart valves that can be delivered through catheter intervention, specifically including a stent and leaflets connected to the stent, the stent is made of memory material such as nickel-titanium alloy, and is a radially deformable cylindrical structure as a whole, with a hollow area on the side wall, for example, formed by laser cutting or weaving, a blood flow channel is located inside the stent, and the leaflets are connected inside the stent, and multiple leaflets cooperate with each other to control the degree of opening and closing of the blood flow channel, and the leaflets can use the artificial heart valve material of the present application. The artificial heart valve material can also be used to process a coating, which is located on the blood inflow side of the leaflet and can be located on the radial inside and / or outside of the stent to maintain sealing, prevent peripheral leakage, and provide safety protection. The coating on the inside of the stent is connected to the leaflet as a separate body or as an integrated structure, and the coating on the outside of the stent can also be formed by rolling up the inner coating.

[0099] Based on this, an embodiment of the present application further provides a method for preparing an artificial heart valve, the artificial heart valve comprising a stent and a plurality of leaflets connected to the stent, the preparation method comprising:

[0100] Providing a polymer film for preparing a leaflet;

[0101] The polymer film is maintained in a predetermined three-dimensional shape and at least the bent portion is subjected to a swelling treatment. After the swelling treatment, the polymer film is maintained in the three-dimensional shape and dried. Alternatively, the polymer film may be directly swollen and then maintained in the predetermined three-dimensional shape and dried.

[0102] The dried polymer film is mounted on a stent to obtain an artificial heart valve.

[0103] The preparation of the polymer membrane, as well as the swelling and drying processes, can be combined with the previous description and will not be further elaborated. Before the dried polymer membrane is mounted on the stent as a leaflet, the membrane can be cut according to the leaflet's contour at any step. This can be done either before cutting and then shaping (including swelling and drying processes), or after shaping and then cutting.

[0104] As for the installation timing of the leaflets, they can be installed on the stent before the swelling treatment or after the drying treatment. Since there are multiple leaflets, the multiple leaflets can be prepared separately (including shaping) and then installed on the stent. Alternatively, the multiple leaflets can be prepared separately, and then connected end to end in sequence to form a cylindrical structure, and then installed on the stent. Of course, an integrated structure can be adopted between the multiple leaflets, that is, they are cut from the same piece of polymer film and kept connected to each other. For example, in one embodiment, a leaflet preform of an artificial heart valve is also provided, which is cylindrical and includes multiple leaflets connected end to end in sequence.

[0105] The leaflet preform is obtained by swelling and drying a cylindrical polymer film. The polymer film can also be pre-cut according to the leaflet contour or cut after being shaped.

[0106] Regarding mounting the leaflets on the stent before the swelling treatment, one embodiment further provides a method for preparing an artificial heart valve, the artificial heart valve comprising a stent and a plurality of leaflets connected to the stent, the preparation method comprising:

[0107] providing a polymer film having a leaflet-shaped contour;

[0108] Mounting the polymer film on a support, maintaining the polymer film in a predetermined three-dimensional shape and performing swelling treatment on at least the bent portion;

[0109] After the swelling treatment, the three-dimensional shape of the polymer film is maintained and the stent is dried to obtain an artificial heart valve.

[0110] Alternatively, the polymer membrane may be directly swollen after being mounted on the support, and then maintained in a predetermined three-dimensional shape using a mold, followed by drying.

[0111] After the artificial heart valve is assembled, it can be heat treated at a temperature of 80-160°C, for example, 120-140°C under inert gas protection, and for a time of 0.5-4 hours, for example, 2 hours.

[0112] The following provides a number of specific embodiments in combination with specific parameters, taking an artificial heart valve as an example, such as a valve in a position such as the aortic valve.

[0113] Example 1

[0114] Dissolve polyurethane in DMAc to form a 10 wt% polyurethane solution. Pour 10 mL of the polyurethane solution into a flat mold (e.g., a 50 mm x 50 mm metal box). Bake the mold at 60°C for 12 hours to form a polyurethane film with a thickness of 0.2 mm.

[0115] Part (a) in Figure 2 shows a leaflet semi-finished product (corresponding to a single leaflet) obtained by laser cutting a polyurethane film according to a predetermined contour shape. The leaflet semi-finished product is placed in a mold with a three-dimensional configuration, which has a support surface adapted to the predetermined three-dimensional shape. The mold and the leaflet semi-finished product are immersed in a 50wt% ethanol solution for 2 hours to complete the swelling treatment.

[0116] After the swelling treatment, the mold together with the leaflet semi-finished product is dried in a dry nitrogen atmosphere at 60°C for 2 hours. The leaflet semi-finished product is taken out, that is, the leaflet semi-finished product is separated from the mold and further dried for 2 hours to obtain the leaflet, see part (b) of Figure 2.

[0117] Multiple leaflets are connected to form a cylindrical structure, as shown in part (c) of Figure 2, and then sutured to a stent to obtain an artificial heart valve, as shown in part (d) of Figure 2. Of course, the relative posture of the leaflets and the stent should be adapted to the predetermined three-dimensional shape.

[0118] Example 2

[0119] A 0.2 mm polyurethane film was prepared in the same manner as in Example 1.

[0120] Referring to parts (a) to (b) of FIG3 , a polyurethane film is laser-cut into a leaflet semi-finished product (corresponding to a single leaflet) according to a predetermined contour shape, and multiple leaflets are connected to each other to form a cylindrical structure, which is then sutured to a stent to obtain an artificial heart valve prefabricated product.

[0121] The artificial heart valve preform is placed in a three-dimensional mold. The mold is roughly cylindrical and extends into the stent to support the leaflet part in a predetermined three-dimensional shape, as shown in part (c) of Figure 3. The mold and the artificial heart valve preform are immersed in a 50wt% ethanol solution for 2 hours to complete the swelling treatment.

[0122] After the swelling treatment, the mold together with the artificial heart valve preform was dried in a dry nitrogen atmosphere at 60° C. for 2 h.

[0123] The artificial heart valve preform obtained is further subjected to heat treatment. The artificial heart valve preform is heated to 120° C. in a dry nitrogen atmosphere and maintained for 2 hours; and then slowly cooled to room temperature.

[0124] Example 3

[0125] A 0.2 mm polyurethane film was prepared in the same manner as in Example 1.

[0126] The polyurethane film is laser cut according to a predetermined contour shape to obtain a leaflet semi-finished product which is connected to each other and can be cut into a plurality of leaflets. The leaflet semi-finished products are connected end to end to form a cylindrical structure.

[0127] The cylindrical structure is placed in a mold with a three-dimensional configuration. The mold is roughly cylindrical. The cylindrical structure is sleeved on the outer periphery of the mold and is placed together with the mold in an 80 wt % ethanol solution and immersed for 1 hour.

[0128] After swelling, the leaflet semi-finished product, along with the mold, is dried in a dry nitrogen atmosphere at 60°C for 2 hours. The leaflet semi-finished product is then separated from the mold and dried for another 2 hours to produce a conjoined multi-leaflet assembly, as shown in Figure 4 (a). This can then be mounted on a stent to produce an artificial heart valve, as shown in Figure 4 (b).

[0129] Example 4

[0130] Polyurethane was dissolved in DMF to form a 15 wt% polyurethane solution. 60 mL of this 15 wt% polyurethane solution was poured into a flat mold (150 mm x 150 mm metal box). The mold was then baked at 60°C in a dry nitrogen atmosphere for 8 hours. This formed a 0.2 mm thick polyurethane film, as shown in Figure 5 (a).

[0131] The polyurethane film is placed in the mold. Taking three leaflets as an example, the mold has at least three adjacent mold cavities to form three leaflets at a time, as shown in part (b) of Figure 5. The polyurethane film and the mold are placed in a 50wt% isopropyl alcohol solution and soaked for 0.5h.

[0132] The mold is removed and dried at 50°C for 5 hours. This results in a pre-formed, integrated membrane (sheet-shaped and containing three leaflets). Excessive portions are trimmed and the membrane is rolled into a tube, as shown in Figure 5 (c). The first and last leaflets are sewn together to form a tube, which is then mounted on a stent to create the artificial heart valve.

[0133] Alternatively, heat treatment may be performed by heating the artificial heart valve to 120° C. in a dry nitrogen atmosphere, maintaining the temperature for 2 hours, and then slowly cooling the temperature to room temperature.

[0134] Example 5

[0135] Dissolve polyurethane in DMF to form a 15wt% polyurethane solution; provide a cylindrical mold according to the size requirements of the valve product, one end of which is connected to a power source, such as a motor that can rotate at a constant speed, and evenly apply the prepared polyurethane solution to the outer or inner surface of the mold (if the mold is a hollow structure, its inner surface can be used as the molding surface), keep the mold rotating at a constant speed around its own axis (the axis is placed horizontally), and dry it at 50°C for 2h; repeat the above dipping and drying process 5 times; finally dry it for 24h; after separation from the mold, a polymer cylinder with uniform thickness is formed, as shown in part (a) of Figure 6, with a cylinder wall thickness of 0.2mm.

[0136] The polymer cylinder was placed into another pre-molded mold that matched the three-dimensional shape of the leaflet, and the pre-molded mold was placed in a 30 wt% aqueous solution of tetrahydrofuran and soaked for 0.5 h.

[0137] The preformed mold is removed and dried at 40°C for 6 hours. This results in a preformed, integrated membrane (cylindrical and including three leaflets) as shown in Figure 6 (b). Excessive portions are trimmed to obtain the integrated leaflets, which are then secured to the stent to create the artificial heart valve.

[0138] The obtained artificial heart valve was further heat-treated by heating it to 140° C. in a dry nitrogen atmosphere and maintaining it for 0.5 h; and then slowly cooling it to room temperature.

[0139] Example 6

[0140] Dissolve polyurethane in DMF to form a 15wt% polyurethane solution; provide a cylindrical mold according to the size requirements of the valve product, one end of which is connected to a power source, such as a motor that can rotate at a constant speed, and evenly apply the prepared polyurethane solution to the outer or inner surface of the mold. Keep the mold rotating at a constant speed around its own axis (the axis is placed horizontally) and dry it at 50°C for 2 hours; repeat the above dipping and drying process 5 times; finally dry it for 24 hours; after separation from the mold, a polymer cylinder with uniform thickness is formed, and the cylinder wall thickness is 0.2mm.

[0141] The polymer cylinder is placed in a 70 wt% ethanol aqueous solution and soaked for 2 hours. The swollen polymer cylinder is then placed in another pre-molded mold that matches the three-dimensional shape of the leaflet.

[0142] The pre-formed mold is dried at 40°C for 6 hours to obtain a pre-formed integrated membrane (cylindrical and including three leaflets). The excess parts are trimmed to obtain the integrated leaflets, which are then fixed to the stent to obtain the artificial heart valve.

[0143] Heat treatment was performed by heating the artificial heart valve to 150°C in a dry nitrogen atmosphere, maintaining it for 0.5 h, and then slowly cooling it to room temperature.

[0144] Example 7

[0145] Dissolve polyurethane in DMAc to form a 10 wt% polyurethane solution. Pour 10 mL of the polyurethane solution into a flat mold (e.g., a 50 mm x 50 mm metal box). Bake the mold at 60°C for 12 hours to form a 0.2 mm thick polyurethane film.

[0146] The leaflet semi-finished product (corresponding to a single leaflet) is laser-cut from a polyurethane film according to a predetermined contour. This semi-finished leaflet is then placed in a three-dimensional mold with a male and female cavity. The mold is closed, with an opening in the cavity and a support surface adapted to the predetermined three-dimensional shape. A 50% propanol solution is injected into the cavity through the opening and allowed to soak for 3 hours to complete the swelling process.

[0147] After the swelling treatment, the propanol solution was poured out and the mixture was dried at 60°C for 4 hours. The mold was opened and the mixture was dried at 60°C for 3 hours to obtain the petals.

[0148] Multiple leaflets are connected to each other to form a cylindrical structure, which is then sutured to a stent to obtain an artificial heart valve. The relative posture of the leaflets and the stent should adapt to the predetermined three-dimensional shape.

[0149] Control group 1

[0150] Dissolve polyurethane in DMAc to form a 10 wt% polyurethane solution. Pour 10 mL of the polyurethane solution into a flat mold (e.g., a 50 mm x 50 mm metal box). Bake the mold at 60°C for 12 hours to form a 0.2 mm thick polyurethane film.

[0151] Control group 2

[0152] 1g of polyurethane solid was placed in a mold with a 50x50mm inner cavity and a height of 0.25mm. The mold was preheated at 210°C for 5 minutes. The pressure was then increased to 1000 psi and maintained for 1 minute. This molding process resulted in a 0.21mm thick membrane.

[0153] Experimental Group 1

[0154] Dissolve polyurethane in DMAc to form a 10 wt% polyurethane solution. Pour 10 mL of this solution into a flat mold (e.g., a 50 mm x 50 mm metal box). Place the mold in a 60°C oven for 12 hours to form a 0.2 mm thick polyurethane film. Secure the membrane to the mold and soak the mold and membrane in a 50 wt% ethanol solution for 2 hours to complete the swelling process. After swelling, dry the mold and the leaflet preform at 60°C for 2 hours in a dry nitrogen atmosphere to obtain the membrane material.

[0155] Performance Comparison

[0156] The breaking strength, elongation at break and suture force of the polyurethane membrane were tested. The test results are shown in Table 1 below.

[0157] Table 1 Performance test results

[0158] Group Breaking strength (MPa) Breaking elongation (%) Sample thickness (mm) Suture force (N) Control group 138.32612.310.205.02 Control group 235.64589.340.214.72 Experimental group 138.53654.320.205.08

[0159] The results from Control Groups 1 and 2 show a slight decrease in the membrane's breaking strength, elongation at break, and suture force after hot pressing. The pressure during hot pressing induces residual stress within the membrane or reduces the material's molecular weight. Comparing the data from Control Group 1 and Experimental Group 1, there are no significant differences in the mechanical properties of the materials after pre-forming. This suggests that pre-forming effectively improves the uniformity and pass rate of leaflet thickness without compromising the membrane's mechanical strength.

[0160] Table 2 Comparison of fluid dynamics properties

[0161]

[0162] Comparative Example 1

[0163] Polyurethane is dissolved in DMAc to form a 10 wt% polyurethane solution. 10 mL of this solution is poured into a flat mold (e.g., a 50 mm x 50 mm metal box). The mold is then baked at 60°C for 12 hours to form a 0.2 mm thick polyurethane film. The polyurethane film is then laser-cut to create the desired leaflet and skirt shape. These are then sewn and mounted onto a stent to create the polymer valve.

[0164] The fluid dynamics results show no significant differences between the various examples, indicating that the order and form of the swelling treatment have little impact on the fluid dynamics performance of the final valve. However, the effective opening area in Comparative Example 1 is reduced, likely due to the large number of leaflet bending variations during opening, resulting in a reduced leaflet opening area. Regurgitation in Comparative Example 1 increases due to increased leakage caused by incomplete leaflet fitting. The transvalvular pressure differential in Comparative Example 1 increases significantly, as the leaflet bending deformation increases during the opening and closing process, placing greater stress on the leaflets and leading to a significant increase in transvalvular pressure differential.

[0165] According to the relevant ISO5840 standards, the fatigue resistance of Examples 1 to 7 and Comparative Example 1 was measured, and the final test results are as follows:

[0166] Example 1: 240 million times, no tearing occurred, and the pores at the seams were relatively large;

[0167] Example 2: 210 million times, tearing at the seam;

[0168] Example 3: 280 million times, no tearing occurred, and the pores at the seams were relatively large;

[0169] Example 4: After 440 million cycles, the leaflet tip was worn out; there was no change at the suture line.

[0170] Example 5: 480 million times, the free edge of the leaflet was torn; there was no change at the suture line;

[0171] Example 6: 450 million times, the free edge of the leaflet was torn; there was no change at the suture line;

[0172] Example 7: 250 million times, no tearing occurred, and the pores at the seams were relatively large;

[0173] Comparative Example 1: 120 million times, the tip of the leaflet was torn, the bend of the leaflet was torn, and there were large gaps at the valve sutures.

[0174] The above results show that the valves prepared in Examples 1-3 and 7 have no tears in the active area of ​​the leaflets, but their fatigue life is affected by the suture part; the results of Examples 4-6 have excellent fatigue performance, which shows that the valve has significantly improved the stress distribution in the active area of ​​the leaflets through swelling and pre-forming, and the life of the leaflets in the active area is longer than that of Comparative Example 1. The leaflets of Comparative Example 1 have multiple tears at the tip and bend. Therefore, the swelling-pre-forming method of the embodiment can effectively avoid the fatigue problem at the bend of the leaflets while ensuring the uniformity of the material thickness.

[0175] The technical features of the above-described embodiments may be combined in any manner. To simplify the description, not all possible combinations of the technical features in the above-described embodiments are described. However, as long as no contradiction exists between these combinations of technical features, they should be considered to be within the scope of this specification. When technical features of different embodiments are embodied in the same drawing, it can be deemed that the drawing also discloses examples of combinations of the various embodiments involved.

[0176] The above-described embodiments merely represent several implementation methods of the present application. While the descriptions are relatively specific and detailed, they should not be construed as limiting the scope of the patent application. It should be noted that a person skilled in the art may make various modifications and improvements without departing from the spirit of the present application, and such modifications and improvements are all within the scope of protection of the present application.

Claims

1. A method for preparing an implantable material, characterized in that: The steps include: Step S100, providing a polymer film; Step S200, performing swelling treatment on the polymer film; Step S300 , maintaining the polymer film in a predetermined three-dimensional shape and performing a drying process to obtain the implantable material.

2. The method for preparing an implantable material according to claim 1, wherein: The preparation method of the polymer film comprises: Dissolving the raw material in a first solvent to prepare a solution with a mass percent concentration of 3% to 40%; forming a film on the surface of the mold using the solution; The polymer film is then obtained by drying.

3. The method for preparing an implantable material according to claim 2, wherein: The raw material is at least one of polyurethane, polyolefin, polysiloxane, polyvinyl alcohol, and Pebax; and the first solvent is selected from a good solvent of the raw material.

4. The method for preparing an implantable material according to claim 2, wherein: The first solvent is at least one of DMAc, DMF, tetrahydrofuran, DMSO, toluene, cyclohexane, xylene, and dichloromethane.

5. The method for preparing an implantable material according to claim 2, wherein: The drying temperature is 25-80° C., and the drying time is 1-48 hours.

6. The method for preparing an implantable material according to claim 2, wherein: Inert gas protection is used during the drying.

7. The method for preparing an implantable material according to claim 1, wherein: The thickness of the polymer film is 0.1-0.6 mm.

8. The method for preparing an implantable material according to claim 1, wherein: The polymer film is a cylindrical structure, and the swelling treatment and the drying treatment are carried out in the cylindrical structure; the cylindrical structure is a prefabricated integral structure or the polymer film is first prefabricated into a sheet structure, and then the sheet structure is curled so that two opposite sides are fixed to each other to form a cylindrical structure.

9. The method for preparing an implantable material according to claim 1, wherein: The swelling and drying of the polymer film are carried out in a sheet-like structure, and then formed into a cylindrical structure.

10. The method for preparing an implantable material according to claim 1, wherein: The polymer film has a predetermined three-dimensional shape with a bent portion, and the swelling treatment is performed to swell at least the bent portion or the entire polymer film.

11. The method for preparing an implantable material according to claim 1, wherein: The polymer film is maintained in a predetermined three-dimensional shape while the polymer film is subjected to a swelling treatment; or the polymer film is maintained in a predetermined three-dimensional shape after the polymer film is subjected to a swelling treatment.

12. The method for preparing an implantable material according to claim 1, wherein: Before performing the swelling treatment on the polymer film, the polymer film is firstly mounted on a mold matching the predetermined three-dimensional shape, and then a treatment liquid for swelling is injected into the mold.

13. The method for preparing an implantable material according to claim 1, wherein: In the swelling treatment, the portion to be treated is immersed in a treatment liquid, which is a poor solvent for the polymer film.

14. The method for preparing an implantable material according to claim 1, wherein: During the swelling treatment, the treated area is soaked in a treatment liquid, wherein the treatment liquid is a second solvent or an aqueous solution of the second solvent, wherein the second solvent is selected from at least one of ethanol, propanol, isopropanol, tetrahydrofuran, acetone, and toluene, and the total concentration of the second solvent in the aqueous solution is greater than or equal to 30% by mass.

15. The method for preparing an implantable material according to claim 1, wherein: The polymer film is partially or entirely swollen until the volume change rate of the treated portion is 0.1%-10%.

16. The method for preparing an implantable material according to claim 1, wherein: The swelling treatment time is 0.1 to 24 hours.

17. The method for preparing an implantable material according to claim 1, wherein: A mold is used to support at least one side of the polymer film so as to maintain a predetermined three-dimensional shape.

18. The method for preparing an implantable material according to claim 1, wherein: The drying temperature is 25-80° C., and the drying time is 0.5-48 hours.

19. The method for preparing an implantable material according to claim 1, wherein: The drying process is carried out under inert gas protection.

20. The method for preparing an implantable material according to claim 1, wherein: During the drying process, the predetermined three-dimensional shape of the polymer film is always maintained.

21. The method for preparing an implantable material according to claim 1, wherein: The drying process includes a relatively early stage and a late stage, and the predetermined three-dimensional shape of the polymer film is maintained at least in the early stage, wherein the early stage accounts for at least 15% of the entire drying process time.

22. An implantable material, characterized in that Obtained by the preparation method of the implantable material according to any one of claims 1 to 21.

23. The implantable material according to claim 22, wherein The implantable material is a leaflet in an artificial heart valve; the leaflet has a relative open shape and a closed shape under the action of fluid, as well as a transition shape during the switching process, and the predetermined three-dimensional shape corresponds to the closed shape or transition shape of the leaflet.

24. The implantable material according to claim 23, wherein The opening area corresponding to the leaflet in the open shape is S1, and the opening area corresponding to the leaflet in the transition shape is S2, and the percentage of S2 to S1 is greater than 0 and less than or equal to 85%.

25. An artificial prosthesis, characterized in that: The implantable material according to claim 22 is used.

26. An artificial heart valve, characterized in that: It comprises a stent and a leaflet connected to the stent, wherein the leaflet is made of the implantable material according to claim 23 or 24.

27. The artificial heart valve according to claim 26, wherein The artificial heart valve further comprises a covering connected to the stent, wherein the covering is made of the implantable material; The covering membrane and the leaflet are connected separately or as an integral structure.

28. The artificial heart valve according to claim 27, wherein The stent is in the shape of a radially deformable tube with a blood flow channel inside. The leaflets are located inside the stent to control the blood flow channel, and the covering is located on the blood inflow side of the leaflets.

29. A method for preparing an artificial heart valve, characterized in that: The artificial heart valve comprises a stent and a plurality of leaflets connected to the stent. The preparation method of the artificial heart valve comprises: Providing a polymer film for preparing a leaflet; performing a swelling treatment on the polymer film; Maintaining the polymer film in a predetermined three-dimensional shape and performing a drying process; The dried polymer film is installed on the stent to obtain the artificial heart valve.

30. The method for preparing an artificial heart valve according to claim 29, wherein: The method further includes cutting the polymer film according to the contour shape of the leaflet in any step before installing the dried polymer film as a leaflet to the stent.

31. The method for preparing an artificial heart valve according to claim 29, wherein: The leaflet is mounted on the stent before the swelling process or after the drying process.

32. The method for preparing an artificial heart valve according to claim 29, wherein: After the multiple leaflets are prepared, they are first connected end to end in sequence to form a cylindrical structure, and then installed on the bracket.

33. The method for preparing an artificial heart valve according to claim 29, wherein: The multiple leaflets form an integrated structure.

34. A method for preparing an artificial heart valve, characterized in that: The artificial heart valve comprises a stent and a plurality of leaflets connected to the stent. The preparation method of the artificial heart valve comprises: providing a polymer film having a leaflet-shaped contour; installing the polymer membrane on the bracket and performing a swelling treatment on the polymer membrane; The artificial heart valve is obtained by maintaining the predetermined three-dimensional shape of the polymer film and performing a drying process together with the stent.

35. The method for preparing an artificial heart valve according to claim 34, wherein: The artificial heart valve further includes a covering connected to the stent, and the covering is made of the artificial heart valve material.

36. The method for preparing an artificial heart valve according to claim 35, wherein: The covering membrane and the leaflet are connected separately or as an integral structure.

37. The method for preparing an artificial heart valve according to claim 35, wherein: The stent is in the shape of a radially deformable tube with a blood flow channel inside. The leaflets are located inside the stent to control the blood flow channel, and the covering is located on the blood inflow side of the leaflets.

38. The method for preparing an artificial heart valve according to claim 35, wherein: The coating is located on the radial inner side and / or outer side of the stent.

39. The method for preparing an artificial heart valve according to claim 34, wherein: The method further includes heat-treating the artificial heart valve at a temperature of 80-160° C., using inert gas protection during the heat treatment, and a heat treatment time of 0.5-4 hours.

40. A leaflet preform of an artificial heart valve, characterized in that: The leaflet preform is cylindrical and includes a plurality of leaflets connected end to end in sequence. The leaflet is prepared using the implantable material according to claim 23 or 24.

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