Artificial valve leaflet material, valve leaflet, valve and preparation method

Abstract

Disclosed in the present application are an artificial valve leaflet material, a valve leaflet, a valve and a preparation method. The artificial valve leaflet material uses polyurethane, and comprises, in the direction of thickness, an inner layer and surface layers located on two opposite sides of the inner layer, wherein the elastic modulus of polyurethane in the surface layers is larger than that of polyurethane in the inner layer. The valve leaflet material presents hydrodynamic performance, biological stability, biocompatibility, creep resistance and fatigue resistance at the same time, thereby having performance required by a heart valve.

Description

Artificial valve leaflet material, valve leaflet, valve and preparation method Technical Field

[0001] The present application relates to the technical field of medical materials, artificial valve leaflet materials, valve leaflets, valves and preparation methods. Background Art

[0002] Polyurethane materials have been widely studied for use in artificial valve leaflets, but their use also presents numerous challenges. Polyurethane molecular chains comprise hard and soft segments. Common failure causes of performance degradation in valves include oxidative degradation of the soft segments, hydrolytic degradation, fatigue (including tearing caused by bending and damage caused by stress concentration induced by surface defects), and creep elongation.

[0003] For the molecular structure of polyurethane materials, if the hard segment content is relatively high (or the urea content is high), it can effectively increase the interaction between the molecular chains, making the material structure more compact and the mechanical properties better. At the same time, as the hard segment content is high and the soft segment content is relatively low, the risk of oxidation and hydrolysis caused by the soft segment's own structure will be reduced accordingly, resulting in significant improvements in the material's biostability, fatigue resistance, creep resistance, and biocompatibility. However, at the same time, when the hard segment content is too high, the material's elastic modulus will also increase, making it difficult to meet the fluid mechanics requirements of the valve leaflet during movement when used as a valve material. Technical issues

[0004] In summary, it is difficult to use a synthetic leaflet material made of polyurethane to simultaneously take into account the fluid mechanics, biostability, biocompatibility, creep resistance and fatigue resistance to achieve the performance required by heart valves. Therefore, there is currently no commercial polyurethane material that has been successfully used in heart valves. Technical Solutions

[0005] The present application provides a synthetic leaflet material that takes into account fluid mechanics, biostability, biocompatibility, creep resistance and fatigue resistance, thereby achieving the performance required of a heart valve.

[0006] An artificial valve leaflet material comprises: the artificial valve leaflet material adopts polyurethane, and comprises an inner layer and surface layers located on two opposite sides of the inner layer in the thickness direction, wherein the elastic modulus of the surface layer polyurethane is greater than the elastic modulus of the inner layer polyurethane.

[0007] Several optional methods are also provided below, but they are not intended to be additional limitations on the above-mentioned overall solution. They are merely further supplements or optimizations. Under the premise that there are no technical or logical contradictions, each optional method can be combined separately for the above-mentioned overall solution, or multiple optional methods can be combined.

[0008] Optionally, the elastic modulus of the surface polyurethane is 10 to 60 MPa greater than that of the inner polyurethane, preferably 10 to 30 MPa.

[0009] Optionally, the elastic modulus of the surface polyurethane is 30 to 100 MPa, preferably 40 to 60 MPa.

[0010] Optionally, the elastic modulus of the inner layer polyurethane is 5 to 30 MPa, preferably 20 to 30 MPa.

[0011] Optional, oxygen permeability of the surface polyurethane ≤ 9*10 9 (cm 2 / sec*cm*Hg).

[0012] Optionally, the molecular chain structures of the surface polyurethane and the inner polyurethane meet at least one of the following conditions:

[0013] a. The hard segment content of the inner layer polyurethane material is less than that of the surface layer polyurethane;

[0014] b. The inner layer polyurethane is prepared using an alcohol chain extender, and the surface layer polyurethane is prepared using an amine chain extender;

[0015] c. The surface polyurethane has a higher degree of cross-linking than the inner polyurethane.

[0016] Optionally, the molecular chain structure of the surface polyurethane includes a hard segment and a soft segment, wherein the hard segment includes a first segment formed by isocyanate and a second segment formed by a chain extender;

[0017] The isocyanate is at least one of toluene diisocyanate (TDI), hexamethylene diisocyanate (HDI), diphenylmethane diisocyanate (MDI), naphthalene diisocyanate (NDI), terephthalate diisocyanate (PPDI), isophorone diisocyanate (IPDI), xylylene diisocyanate (XDI), and triphenylmethane triisocyanate;

[0018] The chain extender is at least one of ethylene glycol, propylene glycol, butanediol, pentanediol, hexanediol, octanediol, ethylenediamine, propylenediamine, butanediamine, pentanediamine, hexanediamine, octanediamine, and 1,3-bis(4-hydroxybutyl)-1,1,3,3-tetramethyldisiloxane (BHTD);

[0019] The soft segment raw material is at least one of DONALO T5651, DONALO T5652, polyethylene glycol (PHMO), polytetramethylene glycol (PTMO), adipic acid polyester diol, succinic acid polyester diol and polydimethylsiloxane diol.

[0020] Optionally, in the molecular chain structure of the surface polyurethane, the isocyanate is one of diphenylmethane diisocyanate, toluene diisocyanate, and hexamethylene diisocyanate.

[0021] Optionally, in the molecular chain structure of the surface polyurethane, the isocyanate is diphenylmethane diisocyanate.

[0022] Optionally, in the molecular chain structure of the surface polyurethane, the chain extender is at least one of ethylenediamine and 1,3-bis(4-hydroxybutyl)-1,1,3,3-tetramethyldisiloxane.

[0023] Optionally, in the molecular chain structure of the surface polyurethane, the chain extender is ethylenediamine and 1,3-bis(4-hydroxybutyl)-1,1,3,3-tetramethyldisiloxane.

[0024] Optionally, in the molecular chain structure of the surface polyurethane, the chain extender is ethylenediamine and 1,3-bis(4-hydroxybutyl)-1,1,3,3-tetramethyldisiloxane, and the molar ratio of ethylenediamine to 1,3-bis(4-hydroxybutyl)-1,1,3,3-tetramethyldisiloxane is 1:0.9~1.1.

[0025] Optionally, in the molecular chain structure of the surface polyurethane, the soft segment raw material is at least one of polydimethylsiloxane and polyethylene glycol.

[0026] Optionally, in the molecular chain structure of the surface polyurethane, the soft segment raw materials are polydimethylsiloxane and polyethylene glycol.

[0027] Optionally, in the molecular chain structure of the surface polyurethane, the soft segment raw materials are polydimethylsiloxane and polyethylene glycol, and the mass ratio of polydimethylsiloxane to polyethylene glycol is 3 to 6:1.

[0028] Optionally, the molecular chain structure of the inner layer polyurethane includes a hard segment and a soft segment, wherein the hard segment includes a first segment formed by isocyanate and a second segment formed by a chain extender;

[0029] The isocyanate is at least one of toluene diisocyanate (TDI), hexamethylene diisocyanate (HDI), diphenylmethane diisocyanate (MDI), naphthalene diisocyanate (NDI), terephthalate diisocyanate (PPDI), isophorone diisocyanate (IPDI), xylylene diisocyanate (XDI), and triphenylmethane triisocyanate;

[0030] The chain extender is at least one of ethylene glycol, propylene glycol, butanediol, pentanediol, hexanediol, octanediol, ethylenediamine, propylenediamine, butanediamine, pentanediamine, hexanediamine, octanediamine, and 1,3-bis(4-hydroxybutyl)-1,1,3,3-tetramethyldisiloxane (BHTD);

[0031] The soft segment raw material is at least one of DONALO T5651, DONALO T5652, polyethylene glycol (PHMO), polytetramethylene glycol (PTMO), adipic acid polyester diol, succinic acid polyester diol and polydimethylsiloxane diol.

[0032] Optionally, in the molecular chain structure of the inner layer polyurethane, the isocyanate is one of diphenylmethane diisocyanate, toluene diisocyanate, and hexamethylene diisocyanate.

[0033] Optionally, in the molecular chain structure of the inner layer polyurethane, the isocyanate is diphenylmethane diisocyanate.

[0034] Optionally, in the molecular chain structure of the inner layer polyurethane, the chain extender is at least one of ethylenediamine and 1,3-bis(4-hydroxybutyl)-1,1,3,3-tetramethyldisiloxane.

[0035] Optionally, in the molecular chain structure of the inner layer polyurethane, the chain extender is ethylenediamine and 1,3-bis(4-hydroxybutyl)-1,1,3,3-tetramethyldisiloxane.

[0036] Optionally, in the molecular chain structure of the inner layer polyurethane, the chain extender is ethylenediamine and 1,3-bis(4-hydroxybutyl)-1,1,3,3-tetramethyldisiloxane, and the molar ratio of ethylenediamine to 1,3-bis(4-hydroxybutyl)-1,1,3,3-tetramethyldisiloxane is 1:0.9~1.1.

[0037] Optionally, in the molecular chain structure of the inner layer polyurethane, the soft segment raw material is at least one of polydimethylsiloxane and polyethylene glycol.

[0038] Optionally, in the molecular chain structure of the inner layer polyurethane, the soft segment raw materials are polydimethylsiloxane and polyethylene glycol.

[0039] Optionally, in the molecular chain structure of the inner layer polyurethane, the soft segment raw materials are polydimethylsiloxane and polyethylene glycol, and the mass ratio of polydimethylsiloxane to polyethylene glycol is 3 to 6:1.

[0040] Optionally, the hard segment content of the surface polyurethane and the inner polyurethane is 30%-60%.

[0041] Optionally, the hard segment content of the surface polyurethane and the inner polyurethane is 35% to 60%.

[0042] Optionally, the isocyanate index of the surface polyurethane and the inner polyurethane is 1.0-1.1.

[0043] Optionally, the isocyanate index of the surface polyurethane and the inner polyurethane is 1.0 to 1.05.

[0044] Optionally, the isocyanate index of the surface polyurethane and the inner polyurethane is 1.0 to 1.02.

[0045] Optionally, the thickness of the artificial valve leaflet material is 75 to 210 microns.

[0046] Optionally, the thickness of the artificial valve leaflet material is 80 to 210 microns, preferably 130 to 200 microns.

[0047] Optionally, the thickness of the inner layer of polyurethane is 70 to 170 microns, and the thickness of the surface layer of polyurethane is 5 to 40 microns.

[0048] The design of the surface polyurethane material provides biostability and biocompatibility for the leaflet material. At the same time, the strong interaction between the internal soft and hard segments limits the movement of the soft segment, reduces its water and oxygen transmission capacity, protects the inner polyurethane, and improves the overall biostability of the leaflet. The design of the inner polyurethane leaflet material is to achieve the fluid performance of the leaflet. Since the inner polyurethane accounts for a higher proportion in the thickness direction, it directly determines the mechanical properties of the leaflet.

[0049] Optionally, the thickness of the inner layer of polyurethane is 70 to 170 microns, and the thickness of the surface layer of polyurethane is 10 to 40 microns.

[0050] Optionally, the thickness of the inner layer of polyurethane is 70 to 150 microns, and the thickness of the surface layer of polyurethane is 5 to 30 microns.

[0051] Optionally, the inner layer includes at least one first sublayer along the thickness direction, each first sublayer is made of the same type of polyurethane, or the elastic modulus of each first sublayer gradually increases from the inside to the outside in the thickness direction at intervals of a predetermined value.

[0052] The elastic modulus can be manipulated by using different hard segments, different chain extenders, or a combination of both. During valve opening and closing, differences in elastic modulus across the thickness create shear forces between layers, affecting their bonding strength. This shear force is directly related to differences in elastic modulus. A gradual increase in elastic modulus disperses this shear force, further improving leaflet durability.

[0053] Optionally, the elastic modulus of each first sub-layer gradually increases by 5 to 10 MPa.

[0054] Optionally, the inner layer includes 1 to 6 first sublayers, each first sublayer is divided into at least two groups, the elastic modulus of each first sublayer in the same group is the same, and the elastic modulus of each group of first sublayers gradually increases from the inside to the outside in the thickness direction at intervals of a predetermined value.

[0055] Optionally, the surface layer includes at least one second sublayer along the thickness direction, each second sublayer is made of the same type of polyurethane, or the elastic modulus of each second sublayer gradually increases from the inside to the outside in the thickness direction at intervals of a predetermined value.

[0056] The elastic modulus can be regulated by using different hard segments, different chain extenders, or a combination of the two. The elastic modulus of the outermost layer can also be regulated by surface modification and surface cross-linking to increase the elastic modulus. During the opening and closing of the valve, the difference in elastic modulus in the thickness direction will cause shear force between the layers, affecting the bonding strength between the layers. This shear force is directly related to the difference in elastic modulus. The gradual increase in elastic modulus will disperse this shear force, further improving the durability of the leaflet.

[0057] Optionally, the elastic modulus of each second sub-layer gradually increases by 5 to 10 MPa.

[0058] Optionally, the surface layer includes 2 to 4 second sublayers, each second sublayer is divided into at least two groups, the elastic modulus of each second sublayer in the same group is the same, and the elastic modulus of each group of second sublayers gradually increases from the inside to the outside in the thickness direction at intervals of a predetermined value.

[0059] Optionally, the hard segment content of the inner layer polyurethane is less than the hard segment content of the surface layer polyurethane.

[0060] Optionally, the hard segment content of the surface layer polyurethane is 45-60%, and the hard segment content of the inner layer polyurethane is 30-45%.

[0061] Optionally, the hard segments in the molecular chain structures of the surface polyurethane and the inner polyurethane are modified in one of the following ways:

[0062] A. Introducing fluorinated side chains;

[0063] B. Introduce a chain extender containing POSS groups.

[0064] Optionally, the introduction of fluorinated side chains is achieved by:

[0065] Add 3% to 10% by mass of fluorinated diisocyanate to the synthetic raw materials of polyurethane.

[0066] Optionally, the introduction of POSS groups is achieved by:

[0067] The chain extender diol having a POSS group is added in an amount of 1% to 3% by mass to the synthetic raw materials of the polyurethane.

[0068] Optionally, the inner layer polyurethane is prepared using an alcohol chain extender, and the surface layer polyurethane is prepared using an amine chain extender.

[0069] Optionally, the alcohol chain extender is at least one of ethylene glycol, propylene glycol, butanediol, pentanediol, hexanediol, octanediol, and 1,3-bis(4-hydroxybutyl)-1,1,3,3-tetramethyldisiloxane (BHTD).

[0070] Optionally, the amine chain extender is at least one of ethylenediamine, propylenediamine, butylenediamine, pentamethylenediamine, hexamethylenediamine, and octanediamine.

[0071] Optionally, the alcohol chain extender is butanediol.

[0072] Optionally, the amine chain extender is ethylenediamine.

[0073] Optionally, the alcohol chain extender is butanediol, and the amine chain extender is ethylenediamine.

[0074] Optionally, the surface polyurethane is cross-linked and modified.

[0075] Optionally, the cross-linking modification of the surface polyurethane is carried out by radiation cross-linking or chemical cross-linking.

[0076] The present application also provides a valve leaflet, which is prepared using the artificial valve leaflet material.

[0077] The present application also provides a valve, comprising:

[0078] Stent, with a blood flow channel inside;

[0079] One or more leaflets, wherein the leaflets are prepared using the artificial leaflet material.

[0080] The present application also provides a method for preparing an artificial valve leaflet material, comprising:

[0081] Step 1: immerse the mold in the first surface polyurethane solution, wait for a predetermined time, take it out, and dry it at 30-80° C. under an inert gas atmosphere to form a film;

[0082] The above step 1 is performed 1 to 9 times to obtain a first surface layer of the artificial valve leaflet material;

[0083] Step 2: immerse the mold in the inner layer polyurethane solution, take it out after staying for a predetermined time, and dry it at 30-80° C. under an inert gas atmosphere to form a film;

[0084] The above step 2 is performed 1 to 9 times to obtain the inner layer of the artificial valve leaflet material;

[0085] Step 3: Install the petal frame onto the mold, then immerse it in the second surface polyurethane solution, wait for a predetermined time, take it out, and dry it at 30-80° C. under an inert gas atmosphere to form a film;

[0086] The above step 3 is performed 1 to 9 times to obtain a second surface layer of the artificial valve leaflet material;

[0087] Step 4: demoulding by immersion in water to obtain the artificial valve leaflet material.

[0088] Several optional methods are also provided below, but they are not intended to be additional limitations on the above-mentioned overall solution. They are merely further supplements or optimizations. Under the premise that there are no technical or logical contradictions, each optional method can be combined separately for the above-mentioned overall solution, or multiple optional methods can be combined.

[0089] Optionally, the hard segment content of the surface layer polyurethane is 45-60%, and the hard segment content of the inner layer polyurethane is 30-45%.

[0090] Optionally, the inner layer polyurethane is prepared using an alcohol chain extender, and the surface layer polyurethane is prepared using an amine chain extender.

[0091] Optionally, the alcohol chain extender is at least one of ethylene glycol, propylene glycol, butanediol, pentanediol, hexanediol, octanediol, and 1,3-bis(4-hydroxybutyl)-1,1,3,3-tetramethyldisiloxane (BHTD).

[0092] Optionally, the amine chain extender is at least one of ethylenediamine, propylenediamine, butylenediamine, pentamethylenediamine, hexamethylenediamine, and octanediamine.

[0093] Optionally, the concentration of the polyurethane solution in the first surface layer is 10-30 w / v%, and the concentration of the polyurethane solution in the second surface layer is 5-15 w / v%.

[0094] Optionally, the concentration of the inner layer polyurethane solution is 10-30 w / v%.

[0095] Optionally, the solvents of the first surface polyurethane solution, the second surface polyurethane solution, and the inner polyurethane solution are each one of N,N-dimethylacetamide (DMAc), dimethylformamide (DMF), dimethyl sulfoxide (DMSO), toluene, and tetrahydrofuran (THF).

[0096] Optionally, in step 1, the drying time is 1 to 6 hours.

[0097] Optionally, in step 2, the drying time is 1 to 6 hours.

[0098] Optionally, in step 3, the drying time is 1 to 12 hours.

[0099] Optionally, in step 1, the predetermined time of staying in the first surface polyurethane solution is 5 to 10 seconds.

[0100] Optionally, in step 2, the predetermined time of staying in the inner layer polyurethane solution is 5 to 10 seconds.

[0101] Optionally, in step 3, the predetermined time of staying in the second surface polyurethane solution is 5 to 10 seconds.

[0102] The present application also provides a method for preparing an artificial valve leaflet material, comprising:

[0103] Step 1, preparing a polyurethane film with an elastic modulus of 5 to 30 MPa and a thickness of 80 to 210 microns;

[0104] Step 2: Cover the surface of the film with an isocyanate solution containing a catalyst, and react at 50-90° C. for 3-5 hours to obtain the artificial valve leaflet material.

[0105] Several optional methods are also provided below, but they are not intended to be additional limitations on the above-mentioned overall solution. They are merely further supplements or optimizations. Under the premise that there are no technical or logical contradictions, each optional method can be combined separately for the above-mentioned overall solution, or multiple optional methods can be combined.

[0106] Optionally, the molecular chain structure of the polyurethane includes a hard segment and a soft segment, wherein the hard segment includes a first segment formed by isocyanate and a second segment formed by a chain extender;

[0107] The isocyanate is at least one of toluene diisocyanate (TDI), hexamethylene diisocyanate (HDI), diphenylmethane diisocyanate (MDI), naphthalene diisocyanate (NDI), terephthalate diisocyanate (PPDI), isophorone diisocyanate (IPDI), xylylene diisocyanate (XDI), and triphenylmethane triisocyanate;

[0108] The chain extender is at least one of ethylene glycol, propylene glycol, butanediol, pentanediol, hexanediol, octanediol, ethylenediamine, propylenediamine, butanediamine, pentanediamine, hexanediamine, octanediamine, and 1,3-bis(4-hydroxybutyl)-1,1,3,3-tetramethyldisiloxane (BHTD);

[0109] The soft segment raw material is at least one of DONALO T5651, DONALO T5652, polyethylene glycol (PHMO), polytetramethylene glycol (PTMO), adipic acid polyester diol, succinic acid polyester diol and polydimethylsiloxane diol.

[0110] Optionally, in the molecular chain structure of the polyurethane, the isocyanate is one of diphenylmethane diisocyanate, toluene diisocyanate, and hexamethylene diisocyanate.

[0111] Optionally, in the molecular chain structure of the polyurethane, the isocyanate is diphenylmethane diisocyanate.

[0112] Optionally, in the molecular chain structure of the polyurethane, the chain extender is at least one of ethylenediamine and 1,3-bis(4-hydroxybutyl)-1,1,3,3-tetramethyldisiloxane.

[0113] Optionally, in the molecular chain structure of the polyurethane, the chain extender is ethylenediamine and 1,3-bis(4-hydroxybutyl)-1,1,3,3-tetramethyldisiloxane.

[0114] Optionally, in the molecular chain structure of the polyurethane, the chain extender is ethylenediamine and 1,3-bis(4-hydroxybutyl)-1,1,3,3-tetramethyldisiloxane, and the molar ratio of ethylenediamine to 1,3-bis(4-hydroxybutyl)-1,1,3,3-tetramethyldisiloxane is 1:0.9~1.1.

[0115] Optionally, in the molecular chain structure of the polyurethane, the soft segment raw material is at least one of polydimethylsiloxane and polyethylene glycol.

[0116] Optionally, in the molecular chain structure of polyurethane, the soft segment raw materials are polydimethylsiloxane and polyethylene glycol.

[0117] Optionally, in the molecular chain structure of the polyurethane, the soft segment raw materials are polydimethylsiloxane and polyethylene glycol, and the mass ratio of polydimethylsiloxane to polyethylene glycol is 3 to 6:1.

[0118] Optionally, the hard segment content of the polyurethane is 30%-60%. The hard segment content of the polyurethane is 35%-60%.

[0119] Optionally, the isocyanate index of the polyurethane is 1.0 to 1.1. The isocyanate index of the polyurethane is 1.0 to 1.05. The isocyanate index of the polyurethane is 1.0 to 1.02.

[0120] Optionally, in step 2, the surface of the film is covered with an isocyanate solution containing a catalyst, and the covering method includes at least one of immersion, coating, and spraying.

[0121] Optionally, in step 2, the surface of the film is covered with an isocyanate solution containing a catalyst, isocyanate is infiltrated within a range of 5 to 30 microns from the surface of the film, and a heating reaction is performed to induce side chain crosslinking.

[0122] Optionally, in step 2, the isocyanate in the isocyanate solution is one of HMDI, MDI, and HDI, and the solvent is at least one of cyclohexane, toluene, ethyl acetate, and cyclohexanone.

[0123] Optionally, in step 2, the concentration of the isocyanate solution is 5 wt.%-20 wt.%.

[0124] The present application provides a method for preparing an artificial valve leaflet material, comprising:

[0125] Step 1, preparing a polyurethane film with an elastic modulus of 5 to 30 MPa and a thickness of 80 to 210 microns;

[0126] Step 2: Cover the surface of the film with an isocyanate solution containing a catalyst and react at 50-90° C. for 1-3 hours;

[0127] Step 3: The product of step 2 is placed in a modifier solution and reacted at 30-50° C. for 12-24 hours to obtain the artificial valve leaflet material.

[0128] Several optional methods are also provided below, but they are not intended to be additional limitations on the above-mentioned overall solution. They are merely further supplements or optimizations. Under the premise that there are no technical or logical contradictions, each optional method can be combined separately for the above-mentioned overall solution, or multiple optional methods can be combined.

[0129] Optionally, the molecular chain structure of the polyurethane includes a hard segment and a soft segment, wherein the hard segment includes a first segment formed by isocyanate and a second segment formed by a chain extender;

[0130] The isocyanate is at least one of toluene diisocyanate (TDI), hexamethylene diisocyanate (HDI), diphenylmethane diisocyanate (MDI), naphthalene diisocyanate (NDI), terephthalate diisocyanate (PPDI), isophorone diisocyanate (IPDI), xylylene diisocyanate (XDI), and triphenylmethane triisocyanate;

[0131] The chain extender is at least one of ethylene glycol, propylene glycol, butanediol, pentanediol, hexanediol, octanediol, ethylenediamine, propylenediamine, butanediamine, pentanediamine, hexanediamine, octanediamine, and 1,3-bis(4-hydroxybutyl)-1,1,3,3-tetramethyldisiloxane (BHTD);

[0132] The soft segment raw material is at least one of DONALO T5651, DONALO T5652, polyethylene glycol (PHMO), polytetramethylene glycol (PTMO), adipic acid polyester diol, succinic acid polyester diol and polydimethylsiloxane diol.

[0133] Optionally, in the molecular chain structure of the polyurethane, the isocyanate is one of diphenylmethane diisocyanate, toluene diisocyanate, and hexamethylene diisocyanate.

[0134] Optionally, in the molecular chain structure of the polyurethane, the isocyanate is diphenylmethane diisocyanate.

[0135] Optionally, in the molecular chain structure of the polyurethane, the chain extender is at least one of ethylenediamine and 1,3-bis(4-hydroxybutyl)-1,1,3,3-tetramethyldisiloxane.

[0136] Optionally, in the molecular chain structure of the polyurethane, the chain extender is ethylenediamine and 1,3-bis(4-hydroxybutyl)-1,1,3,3-tetramethyldisiloxane.

[0137] Optionally, in the molecular chain structure of the polyurethane, the chain extender is ethylenediamine and 1,3-bis(4-hydroxybutyl)-1,1,3,3-tetramethyldisiloxane, and the molar ratio of ethylenediamine to 1,3-bis(4-hydroxybutyl)-1,1,3,3-tetramethyldisiloxane is 1:0.9~1.1.

[0138] Optionally, in the molecular chain structure of the polyurethane, the soft segment raw material is at least one of polydimethylsiloxane and polyethylene glycol.

[0139] Optionally, in the molecular chain structure of polyurethane, the soft segment raw materials are polydimethylsiloxane and polyethylene glycol.

[0140] Optionally, in the molecular chain structure of the polyurethane, the soft segment raw materials are polydimethylsiloxane and polyethylene glycol, and the mass ratio of polydimethylsiloxane to polyethylene glycol is 3 to 6:1.

[0141] Optionally, the hard segment content of the polyurethane is 30%-60%. The hard segment content of the polyurethane is 35%-60%.

[0142] Optionally, the isocyanate index of the polyurethane is 1.0 to 1.1. The isocyanate index of the polyurethane is 1.0 to 1.05. The isocyanate index of the polyurethane is 1.0 to 1.02.

[0143] Optionally, in step 2, the isocyanate in the isocyanate solution is one of HMDI, MDI, and HDI, and the solvent is one of cyclohexane, toluene, ethyl acetate, and cyclohexanone.

[0144] Optionally, in step 2, the concentration of the isocyanate solution is 5 wt.% to 20 wt.%.

[0145] Optionally, the modifier in step 3 is one of 3-aminopropyltriethoxysilane, fluorinated alcohol, sphingosine phosphorylcholine, and 3-((tert-butyldimethylsilyl)oxy)-propanol.

[0146] Optionally, the solvent of the modifier in step 3 is at least one of cyclohexane, toluene, DMF, DMAc, and DMSO.

[0147] The present application provides a method for preparing a leaflet, comprising:

[0148] Step 1: immerse the mold in the first surface polyurethane solution, wait for a predetermined time, take it out, and dry it at 30-80° C. under an inert gas atmosphere to form a film;

[0149] The above step 1 is performed 1 to 9 times to obtain a first surface layer of the artificial valve leaflet material;

[0150] Step 2: immerse the mold in the inner layer polyurethane solution, take it out after staying for a predetermined time, and dry it at 30-80° C. under an inert gas atmosphere to form a film;

[0151] The above step 2 is performed 1 to 9 times to obtain the inner layer of the artificial valve leaflet material;

[0152] Step 3: Cut into leaflet shapes and install the leaflet frame on the mold;

[0153] Step 4, then immersing it in the second surface polyurethane solution, taking it out after staying for a predetermined time, and drying it at 30-80° C. under an inert gas atmosphere to form a film;

[0154] The above step 4 is performed 1 to 9 times to obtain a second surface layer of the artificial valve leaflet material;

[0155] Step 5: Demolding by soaking in water to obtain the petals.

[0156] The present application provides a method for preparing a valve, comprising:

[0157] Step 1: immerse the mold in the first surface polyurethane solution, wait for a predetermined time, take it out, and dry it at 30-80° C. under an inert gas atmosphere to form a film;

[0158] The above step 1 is performed 1 to 9 times to obtain a first surface layer of the artificial valve leaflet material;

[0159] Step 2: immerse the mold in the inner layer polyurethane solution, take it out after staying for a predetermined time, and dry it at 30-80° C. under an inert gas atmosphere to form a film;

[0160] The above step 2 is performed 1 to 9 times to obtain the inner layer of the artificial valve leaflet material;

[0161] Step 3: Cut into leaflet shapes and install the leaflet frame on the mold;

[0162] Step 4, then immersing it in the second surface polyurethane solution, taking it out after staying for a predetermined time, and drying it at 30-80° C. under an inert gas atmosphere to form a film;

[0163] The above step 4 is performed 1 to 9 times to obtain a second surface layer of the artificial valve leaflet material;

[0164] Step 5: soaking in water and demoulding to obtain the valve.

[0165] The present invention adjusts the hard segment content and chain extender type in the surface polyurethane and the inner polyurethane, or modifies the surface of the surface polyurethane, or cross-links the surface of the surface polyurethane. Compared with the performance of the inner polyurethane, the elastic modulus of the surface polyurethane is improved, so that the molecular chain structure of the leaflet surface material has a greater force, the bonding between the molecular chains is greater, the material is tighter, it is less likely to cause defects on the leaflet surface, and the stability of the leaflet itself is improved. Through the design and modification of the surface and inner polyurethane materials, the preparation of a multi-layer composite multifunctional bionic leaflet is achieved.

[0166] Compared with the existing technology, the detailed mechanism is as follows:

[0167] 1) Compared to the softer inner layer of polyurethane material, the surface polyurethane material has an increased hard segment content, which reduces the soft segment content susceptible to oxidative hydrolysis, making it more stable. The force exerted by the hard segment on each soft segment increases, making it less likely to move and making it difficult for water and oxygen to be transported through the surface to the interior. This protects the softer inner polyurethane layer from oxidation. The restricted movement of the soft segments also reduces the possibility of relative displacement between soft segments, improving creep resistance. This results in a soft leaflet inner layer (the inner layer polyurethane material has a high soft segment content) and a leaflet surface (the surface polyurethane material has a high hard segment content) with better tolerance, enabling the preparation of a multi-layer composite multifunctional bionic leaflet.

[0168] 2) The polyurethane material of the leaflet surface layer uses some amines as chain extenders. Amines and isocyanates produce urea bonds. Urea bonds produce twice as many hydrogen bonds as urethane bonds, significantly increasing the interaction between the hard and soft segments, resulting in a stronger surface polyurethane material. Furthermore, the soft segments in the molecular structure are less mobile, making it difficult for water and oxygen to be transported through the surface to the interior, thus protecting the internal polyurethane from oxidation. Compared to the inner layer material, the surface material uses amine chain extenders, so the movement of the soft segments in the polyurethane surface material is restricted by urea bonds, reducing the possibility of relative displacement between soft segments. This effectively improves the creep resistance of the leaflet surface material, thereby effectively improving the protection of the inner layer of the leaflet, achieving the preparation of a bionic leaflet with a soft inner layer and a protected outer layer, and realizing the preparation of a multi-layer composite multifunctional bionic leaflet.

[0169] 3) By cross-linking the polyurethane material on the surface of the leaflet, the interaction force between the surface polyurethane molecular chains is greatly increased, thereby improving the strength of the leaflet surface and reducing the probability of hydrolysis of the inner layer polyurethane material with higher softness due to water and oxygen invasion. The increased interaction force between the surface polyurethane molecular chains also limits the occurrence of creep, thereby obtaining an integrated polyurethane leaflet design with effective protection tolerance on the surface and soft and flexible leaflet movement performance on the inner layer. This enables the artificial leaflet material to have better biostability, biocompatibility, creep resistance, and fatigue resistance, thereby realizing the preparation of a multi-layer composite multifunctional bionic leaflet.

[0170] 4) By introducing isocyanate into the polyurethane material of the leaflet surface and then modifying it, side chains are actually added to the main chain, which increases the steric hindrance between the chain segments. The presence of side chains weakens the mobility between chains, improves the tolerance of the surface polyurethane material, thereby reducing the ability to transmit water and oxygen inside the polyurethane and reducing creep. At the same time, the side chains tend to be distributed in the inner layer of the surface to achieve an integrated polyurethane leaflet design with soft and flexible leaflet movement performance. Therefore, it can also play a role in further protecting the interior, improve the overall biological stability, and realize the preparation of a multi-layer composite multifunctional bionic leaflet. Beneficial effects

[0171] The synthetic leaflet material provided in this application can effectively improve the tolerance of the leaflet surface by controlling the hard segment content of the surface polyurethane, the type of chain extender, grafting modification, and cross-linking, while the polyurethane of the inner layer of the leaflet is relatively soft, achieving effective and flexible movement. Since the proportion of the surface layer relative to the overall thickness of the leaflet is small, it takes into account the fluid mechanics properties, biostability, biocompatibility, creep resistance, and fatigue resistance, thereby achieving the leaflet performance required for a heart valve and realizing the preparation of a multi-layer composite multifunctional bionic leaflet. BRIEF DESCRIPTION OF THE DRAWINGS

[0172] FIG1 is a SEM image of the leaflet material prepared in Example 1 after oxidation resistance testing;

[0173] FIG2 is a SEM image of the leaflet material prepared in Example 2 after oxidation resistance testing;

[0174] FIG3 is a SEM image of the leaflet material prepared in Example 3 after oxidation resistance testing;

[0175] FIG4 is a SEM image of the leaflet material prepared in Example 4 after oxidation resistance testing;

[0176] FIG5 is a SEM image of the leaflet material prepared in Example 5 after oxidation resistance testing;

[0177] FIG6 is a SEM image of the leaflet material prepared in Example 6 after oxidation resistance testing;

[0178] FIG7 is a SEM image of the leaflet material prepared in Comparative Example 1 after oxidation resistance testing;

[0179] FIG8 is a SEM image of the leaflet material prepared in Comparative Example 2 after oxidation resistance testing;

[0180] FIG9 is a schematic diagram of the petal frame being fitted onto the mold;

[0181] FIG10 is a schematic diagram of the structure of the leaflet material. Modes for Carrying Out the Invention

[0182] 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.

[0183] In order to better describe and illustrate the embodiments of the present application, reference may be made to one or more drawings, but the additional details or examples used to describe the drawings should not be considered as limiting the scope of the invention of the present application, any of the currently described embodiments or preferred methods.

[0184] 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.

[0185] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as those 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.

[0186] As shown in Figure 10, an artificial valve leaflet material includes: the artificial valve leaflet material is made of polyurethane, and includes an inner layer 200 and a surface layer 100 located on two opposite sides of the inner layer in the thickness direction, and the elastic modulus of the surface layer polyurethane is greater than the elastic modulus of the inner layer polyurethane.

[0187] The artificial leaflet material provided in the present application adopts a multi-layer composite structure. The polyurethane located on the surface has a larger elastic modulus, while the polyurethane located on the inner layer has a smaller elastic modulus. The performance of the surface polyurethane and the inner polyurethane materials complement each other, similar to the structural design of natural leaflet leaflets. The inner layer with a smaller elastic modulus ensures the softness of the leaflet and ensures the normal opening and closing of the leaflet. The surface polyurethane has more stable biocompatibility and biostability. Moreover, since the thickness of the surface polyurethane is smaller than the overall thickness, it has little effect on the overall softness. The lower water and oxygen permeability of the surface polyurethane well protects the inner polyurethane. Therefore, the polyurethane valve with a multi-layer composite structure can take into account fluid mechanics, biostability, biocompatibility, creep resistance and fatigue resistance at the same time.

[0188] A material's biostability, fatigue resistance, biocompatibility, and creep resistance are related to its elastic modulus. Macroscopically, the elastic modulus characterizes how easily a material undergoes elastic deformation under a given stress; a higher elastic modulus indicates greater resistance to deformation. From the perspective of interatomic interactions, the elastic modulus characterizes the strength of the material's internal bonding. Therefore, a higher elastic modulus indicates greater internal bonding within the polyurethane, weaker soft segment mobility, weaker water and oxygen transport within the polyurethane, and less contact with water and oxygen within the polyurethane. Consequently, the material's biostability is relatively high. Furthermore, due to strong intermolecular forces, small molecules are trapped within the polymer, making it less likely to release small molecules that could cause immune problems, resulting in better biocompatibility. The irreversible portion of creep deformation is primarily caused by displacement between molecular chains. Stronger intermolecular forces make chain displacement more difficult, significantly improving creep resistance. As can be seen from the above, a higher elastic modulus significantly improves biostability, fatigue resistance, biocompatibility, and creep resistance. For example, in this design, because the surface polyurethane directly contacts blood, a polyurethane with a high elastic modulus is used, allowing it to simultaneously meet the requirements for biostability, fatigue resistance, biocompatibility, and creep resistance. At the same time, a polyurethane with a lower elastic modulus is used as the inner layer, providing greater flexibility (biological valves are inherently soft), thereby imparting excellent fluid dynamics to the leaflet as a whole, thereby ensuring the excellent fluid dynamics of the multilayer artificial valve leaflet material as a whole.

[0189] The creep process of a material is primarily caused by three types of deformation: general elastic deformation, hyperelastic deformation, and viscous flow. General elastic deformation results from changes in bond angles and bond lengths. The deformation is small, but it recovers immediately after the external force is removed. Hyperelastic deformation results from the gradual extension of the molecular chain through segmental motion. The deformation is much larger than general elastic deformation, and the deformation is exponentially related to time. After the external force is removed, the hyperelastic deformation can slowly recover. Viscous flow results from the relative movement between molecular chains, and the process is irreversible. Because the surface polyurethane has a higher hard segment content, contains amine chain extenders, or has been modified and cross-linked, the intermolecular forces within the surface polyurethane are increased, making relative movement between molecular chains more difficult, reducing the ability to undergo viscous flow, and improving the product's creep resistance.

[0190] In addition, since the movement of the leaflet follows the beating of the heart and requires periodic bending, the artificial leaflet material prepared is required to have good bending resistance. The design of this scheme can make the surface layer produce a larger bending deformation relative to the inner layer when the artificial leaflet material bends. The surface layer uses polyurethane with a higher elastic modulus, that is, a harder polyurethane, which is more resistant to bending, thereby improving the overall bending resistance of the artificial leaflet material.

[0191] The elastic modulus of the surface polyurethane layer is 10 to 60 MPa greater than that of the inner polyurethane layer, preferably 10 to 30 MPa.

[0192] The elastic modulus of the surface polyurethane is 30 to 100 MPa, preferably 40 to 60 MPa, and the elastic modulus of the inner polyurethane is 5 to 30 MPa, preferably 20 to 30 MPa.

[0193] The oxygen permeability of the surface polyurethane is ≤9*10 9 (cm 2 / sec*cm*Hg).

[0194] The inner layer of polyurethane does not directly contact the implant environment. Therefore, the oxygen that the inner layer of polyurethane is exposed to mainly depends on the permeability of the surface polyurethane. The worse the permeability of the surface polyurethane, the lower the water and oxygen content that the inner layer of polyurethane is exposed to, and the less likely the inner layer is to be hydrolyzed and oxidized. The transport of substances inside polyurethane is mainly through the soft segment. The substances exist in the gaps of the soft segment. During the movement of the soft segment, the substances are transferred from one side to the other. Therefore, the permeability of polyurethane depends on the content of the soft segment and the mobility of the soft segment. It is also related to the transported substance. Generally, the better the affinity, the better the compatibility, the larger the transport volume, the better the permeability. Here, the transported substance is certain, which is water (causing hydrolysis) and / or oxygen (causing oxidation). Therefore, in order to reduce the permeability of the surface polyurethane, hydrophobic soft segments, fewer soft segments, and stronger intermolecular forces are mainly selected. At the same time, in order to ensure biocompatibility, the choice of surface polyurethane soft segments is limited. Therefore, more attention is paid to reducing the hard segment content of the surface polyurethane, or enhancing the interaction between the soft and hard segments, for example, increasing urea bonds, increasing cross-linking, increasing branched chain pinning effects, etc.

[0195] Due to the influence of leaflet design on the overall performance of the leaflet, the molecular chain structure of the surface polyurethane and inner polyurethane of the prepared leaflet material is required to meet at least one of the following conditions:

[0196] a. The hard segment content of the inner layer polyurethane is less than that of the surface layer polyurethane;

[0197] b. The inner layer polyurethane is prepared using an alcohol chain extender, and the surface layer polyurethane is prepared using an amine chain extender;

[0198] c. The surface polyurethane has a higher degree of cross-linking than the inner polyurethane.

[0199] In condition b, the amine chain extender includes a single amine chain extender and also includes both an amine chain extender and an alcohol chain extender.

[0200] In condition c, the difference between the surface polyurethane and the inner polyurethane lies in the degree of cross-linking, which includes the case where the surface polyurethane is cross-linked and the inner polyurethane is not cross-linked, and also includes the case where both the surface polyurethane and the inner polyurethane are cross-linked, and the degree of cross-linking of the surface polyurethane is higher than that of the inner polyurethane. Except for the difference in degree of cross-linking, there is no significant difference in other molecular structures between the surface polyurethane and the inner polyurethane.

[0201] The three conditions a, b, and c can be met at the same time, or only two of them can be met, or only one of them can be met. If any one of the conditions a, b, and c is met, the surface polyurethane and the inner polyurethane can exhibit different elastic moduli.

[0202] The design of the surface polyurethane material provides biostability and biocompatibility for the leaflet material. At the same time, the strong interaction between the internal soft and hard segments limits the movement of the soft segment, reduces its water and oxygen transmission capacity, protects the inner polyurethane, and improves the overall biostability of the leaflet. The design of the inner polyurethane leaflet material is to achieve the fluid performance of the leaflet. Since the inner polyurethane accounts for a higher proportion in the thickness direction, it directly determines the mechanical properties of the leaflet.

[0203] The molecular chain structure of the surface polyurethane includes a hard segment and a soft segment, wherein the hard segment includes a first segment formed by isocyanate and a second segment formed by a chain extender;

[0204] The isocyanate is at least one of toluene diisocyanate (TDI), hexamethylene diisocyanate (HDI), diphenylmethane diisocyanate (MDI), naphthalene diisocyanate (NDI), terephthalate diisocyanate (PPDI), isophorone diisocyanate (IPDI), xylylene diisocyanate (XDI), and triphenylmethane triisocyanate;

[0205] The chain extender is at least one of ethylene glycol, propylene glycol, butanediol, pentanediol, hexanediol, octanediol, ethylenediamine, propylenediamine, butanediamine, pentanediamine, hexanediamine, octanediamine, and 1,3-bis(4-hydroxybutyl)-1,1,3,3-tetramethyldisiloxane (BHTD);

[0206] The soft segment raw material is at least one of DONALO T5651, DONALO T5652, polyethylene glycol (PHMO), polytetramethylene glycol (PTMO), adipic acid polyester diol, succinic acid polyester diol and polydimethylsiloxane diol.

[0207] In the molecular chain structure of the surface polyurethane, the isocyanate is one of diphenylmethane diisocyanate, toluene diisocyanate and hexamethylene diisocyanate.

[0208] In the molecular chain structure of the surface polyurethane, the isocyanate is diphenylmethane diisocyanate.

[0209] In the molecular chain structure of the surface polyurethane, the chain extender is at least one of ethylenediamine and 1,3-bis(4-hydroxybutyl)-1,1,3,3-tetramethyldisiloxane.

[0210] In the molecular chain structure of the surface polyurethane, the chain extender is ethylenediamine and 1,3-bis(4-hydroxybutyl)-1,1,3,3-tetramethyldisiloxane.

[0211] In the molecular chain structure of the surface polyurethane, the chain extender is ethylenediamine and 1,3-bis(4-hydroxybutyl)-1,1,3,3-tetramethyldisiloxane, and the molar ratio of ethylenediamine to 1,3-bis(4-hydroxybutyl)-1,1,3,3-tetramethyldisiloxane is 1:0.9-1.1.

[0212] In the molecular chain structure of the surface polyurethane, the soft segment raw material is at least one of polydimethylsiloxane and polyethylene glycol.

[0213] In the molecular chain structure of the surface polyurethane, the soft segment raw materials are polydimethylsiloxane and polyethylene glycol.

[0214] In the molecular chain structure of the surface polyurethane, the soft segment raw materials are polydimethylsiloxane and polyethylene glycol, and the mass ratio of polydimethylsiloxane to polyethylene glycol is 3 to 6:1.

[0215] The molecular chain structure of the inner layer polyurethane includes a hard segment and a soft segment, wherein the hard segment includes a first segment formed by isocyanate and a second segment formed by a chain extender;

[0216] The isocyanate is at least one of toluene diisocyanate (TDI), hexamethylene diisocyanate (HDI), diphenylmethane diisocyanate (MDI), naphthalene diisocyanate (NDI), terephthalate diisocyanate (PPDI), isophorone diisocyanate (IPDI), xylylene diisocyanate (XDI), and triphenylmethane triisocyanate;

[0217] The chain extender is at least one of ethylene glycol, propylene glycol, butanediol, pentanediol, hexanediol, octanediol, ethylenediamine, propylenediamine, butanediamine, pentanediamine, hexanediamine, octanediamine, and 1,3-bis(4-hydroxybutyl)-1,1,3,3-tetramethyldisiloxane (BHTD);

[0218] The soft segment raw material is at least one of DONALO T5651, DONALO T5652, polyethylene glycol (PHMO), polytetramethylene glycol (PTMO), adipic acid polyester diol, succinic acid polyester diol and polydimethylsiloxane diol.

[0219] In the molecular chain structure of the inner layer polyurethane, the isocyanate is one of diphenylmethane diisocyanate, toluene diisocyanate and hexamethylene diisocyanate.

[0220] In the molecular chain structure of the inner layer polyurethane, the isocyanate is diphenylmethane diisocyanate.

[0221] In the molecular chain structure of the inner layer polyurethane, the chain extender is at least one of ethylenediamine and 1,3-bis(4-hydroxybutyl)-1,1,3,3-tetramethyldisiloxane.

[0222] In the molecular chain structure of the inner layer polyurethane, the chain extender is ethylenediamine and 1,3-bis(4-hydroxybutyl)-1,1,3,3-tetramethyldisiloxane.

[0223] In the molecular chain structure of the inner layer polyurethane, the chain extender is ethylenediamine and 1,3-bis(4-hydroxybutyl)-1,1,3,3-tetramethyldisiloxane, and the molar ratio of ethylenediamine to 1,3-bis(4-hydroxybutyl)-1,1,3,3-tetramethyldisiloxane is 1:0.9-1.1.

[0224] In the molecular chain structure of the inner layer polyurethane, the soft segment raw material is at least one of polydimethylsiloxane and polyethylene glycol.

[0225] In the molecular chain structure of the inner layer polyurethane, the soft segment raw materials are polydimethylsiloxane and polyethylene glycol.

[0226] In the molecular chain structure of the inner layer polyurethane, the soft segment raw materials are polydimethylsiloxane and polyethylene glycol, and the mass ratio of polydimethylsiloxane to polyethylene glycol is 3 to 6:1.

[0227] The hard segment content of the surface polyurethane and the inner polyurethane is 30%-60%.

[0228] The hard segment content of the surface polyurethane and the inner polyurethane is 35% to 60%.

[0229] The isocyanate index of the surface polyurethane and the inner polyurethane is 1.0 to 1.1.

[0230] The isocyanate index of the surface polyurethane and the inner polyurethane is 1.0 to 1.05.

[0231] The isocyanate index of the surface polyurethane and the inner polyurethane is 1.0 to 1.02.

[0232] The thickness of the artificial valve leaflet material is 75 to 210 microns.

[0233] The thickness of the artificial valve leaflet material is 80 to 210 microns, preferably 130 to 200 microns.

[0234] The thickness of the inner layer polyurethane is 70 to 170 microns, and the thickness of the surface layer polyurethane is 5 to 40 microns.

[0235] The thickness of the inner layer polyurethane is 70 to 170 microns, and the thickness of the surface layer polyurethane is 10 to 40 microns.

[0236] The thickness of the inner layer of polyurethane is 70 to 150 microns, and the thickness of the surface layer of polyurethane is 5 to 30 microns.

[0237] Surface polyurethane is provided on two opposite sides of the inner polyurethane layer. The thickness of the surface polyurethane refers to the thickness of the surface polyurethane on one side of the inner polyurethane layer, rather than the sum of the thicknesses of the surface polyurethane on both sides of the inner polyurethane layer.

[0238] The thickness of the surface polyurethane needs to meet at least two requirements. On the one hand, it should not be too thick to adversely affect the overall softness of the artificial valve leaflet material. On the other hand, it should not be too thin to affect the effective blocking of blood oxygen in the blood environment and form effective protection for the inner layer of polyurethane.

[0239] The appropriate thickness distribution of the inner layer polyurethane and the surface layer polyurethane enables the artificial valve leaflet material as a whole to have good fluid mechanical properties and meet the requirements of biostability, biocompatibility, creep resistance and fatigue resistance.

[0240] The inner layer includes at least one first sublayer along the thickness direction, each first sublayer being made of the same polyurethane material, or having an elastic modulus that gradually increases at predetermined intervals from the inside to the outside of the thickness direction. Referring to FIG. 10 , when used in this application, "from inside to outside" refers to extending from the centerline in the thickness direction in the direction indicated by the arrow, i.e., from inside to outside.

[0241] In the thickness direction, the direction extending from the center of the artificial valve leaflet material to the outside, that is, from the inside to the outside in the thickness direction.

[0242] The elastic modulus of each first sub-layer increases gradually with an interval of 5 to 10 MPa.

[0243] The inner layer includes 1 to 6 first sublayers, each first sublayer is divided into at least two groups, the elastic modulus of each first sublayer in the same group is the same, and the elastic modulus of each group of first sublayers gradually increases from the inside to the outside in the thickness direction at intervals of a predetermined value.

[0244] The surface layer includes at least one second sublayer along the thickness direction, and each second sublayer is made of the same polyurethane material, or the elastic modulus of each second sublayer gradually increases from the inside to the outside in the thickness direction at intervals of a predetermined value.

[0245] The elastic modulus of each second sub-layer increases gradually with an interval of 5 to 10 MPa.

[0246] The surface layer includes 2 to 4 second sublayers, each second sublayer is divided into at least two groups, the elastic modulus of each second sublayer in the same group is the same, and the elastic modulus of each group of second sublayers gradually increases from the inside to the outside in the thickness direction at intervals of predetermined values.

[0247] The first sub-layer and the second sub-layer are layer structures formed based on the process during the preparation process. For example, a first sub-layer or a second sub-layer is formed by performing one dip coating and drying.

[0248] The hard segment content of the inner layer polyurethane is less than that of the surface layer polyurethane.

[0249] The surface polyurethane has a large elastic modulus, which can be achieved by increasing the hard segment content. The relatively high hard segment content increases the interaction between the molecular chains, making the material structure denser, less prone to defects, and the location of calcification deposition smaller, and the biocompatibility is relatively better. At the same time, due to the increase in the interaction between the molecular chains, the biological stability, fatigue resistance and creep resistance are also correspondingly better.

[0250] At the same time, a higher hard segment content also means a lower soft segment content. The problems of easy oxidation and hydrolysis caused by the soft segment's own structure are also reduced accordingly, and the material's biological stability, fatigue resistance, creep resistance and biocompatibility are significantly improved.

[0251] The inner layer of polyurethane has a smaller hard segment content and better softness. Under blood flushing, it has better fluid mechanics properties. The inner layer of polyurethane and the surface layer of polyurethane cooperate with each other, taking into account fluid mechanics properties, biostability, biocompatibility, creep resistance and fatigue resistance.

[0252] For polyurethane materials, a high water and oxygen content will cause oxidation and hydrolysis problems of the soft segment. In order to reduce the oxidation and hydrolysis problems of the soft segment, it is necessary to reduce the water and oxygen content inside the artificial valve leaflet material as much as possible. In terms of the use environment, the surface polyurethane is exposed to much more water and oxygen than the inner layer. The surface polyurethane has a higher hard segment content and a stronger force between molecular chains, which can better resist the entry of water and oxygen. Even if the inner layer polyurethane has a relatively high soft segment content, it is not easily exposed to water and oxygen, and the corresponding oxidation and hydrolysis problems will be significantly reduced.

[0253] The hard segment content of the surface layer polyurethane is 45-60%, and the hard segment content of the inner layer polyurethane is 30-45%.

[0254] The hard segments in the molecular chain structure of the surface polyurethane and the inner polyurethane are modified in one of the following ways:

[0255] A. Introducing fluorinated side chains;

[0256] B. Introduce a chain extender containing POSS groups.

[0257] The introduction of fluorinated side chains is achieved by:

[0258] Add 3% to 10% by mass of fluorinated diisocyanate to the synthetic raw materials of polyurethane.

[0259] The fluorinated diisocyanate is prepared using existing technology, for example, by using triisocyanate and fluorinated alcohol (for example, 4-fluorobenzyl alcohol, CAS No.: 459-56-3, or 1H,1H-perfluorododecane-1-ol, CAS No.: 423-65-4).

[0260] Fluorinated side chains can cause a pinning effect, making it difficult for the soft segments of polyurethane to move. As a result, the hardness and strength of polyurethane are improved. At the same time, fluorinated side chains can also bring about a steric effect, tending to the surface of polyurethane. Since the fluorinated groups have excellent hydrophobicity, it increases the difficulty of water invading the interior of polyurethane, thereby improving the material's resistance to hydrolysis.

[0261] The introduction of POSS groups is achieved by:

[0262] The chain extender diol having a POSS group is added in an amount of 1% to 3% by mass to the synthetic raw materials of the polyurethane.

[0263] The chain extender (diol) containing POSS groups can be: trans-cyclohexanediol heptyl-cage polysilsesquioxane, CAS No.: 408439-48-3.

[0264] A small amount of POSS groups is similar to adding inorganic fillers to polymer materials, which greatly increases the strength and wear resistance of polyurethane, while also improving the hardness. Due to the steric hindrance effect, POSS tends to be arranged on the surface of polyurethane. The siloxane in POSS provides polyurethane with excellent biostability and biocompatibility.

[0265] Modifying the hard segments in the molecular chain structure of the surface polyurethane and the inner polyurethane can increase the elastic modulus of the polyurethane and simultaneously improve the biostability and biocompatibility of the polyurethane material.

[0266] The inner layer polyurethane is prepared by using an alcohol chain extender, and the surface layer polyurethane is prepared by using an amine chain extender (which may be an amine chain extender alone or a mixture of amine and alcohol chain extenders).

[0267] The alcohol chain extender is at least one of ethylene glycol, propylene glycol, butanediol, pentanediol, hexanediol, octanediol, and 1,3-bis(4-hydroxybutyl)-1,1,3,3-tetramethyldisiloxane (BHTD).

[0268] The amine chain extender is at least one of ethylenediamine, propylenediamine, butylenediamine, pentamethylenediamine, hexamethylenediamine, and octanediamine.

[0269] The alcohol chain extender is butanediol.

[0270] The amine chain extender is ethylenediamine.

[0271] The alcohol chain extender is butanediol, and the amine chain extender is ethylenediamine.

[0272] Polyurethanes prepared using different chain extenders result in different interactions between the soft and hard segments. When using amine chain extenders, the hard segment forms urea bonds, each of which can form two hydrogen bonds with the soft segment. When using alcohol chain extenders, the hard segment forms urethane bonds, each of which can only form one hydrogen bond with the soft segment. Therefore, urea bonds provide far greater intermolecular forces than urethane bonds. Stronger intermolecular forces result in higher elastic moduli, while weaker intermolecular forces result in lower elastic moduli. Polyurethanes with higher elastic moduli are used as the surface polyurethane, while those with lower elastic modulus are used as the inner polyurethane. The surface polyurethane has stronger interactions between the soft and hard segments, resulting in a denser structure, making it difficult for external water and oxygen to penetrate, thus protecting the inner polyurethane. Furthermore, the higher interactions between the molecular chains in the surface polyurethane also limit the creep of the valve leaflet as a whole, improving the overall anti-creep performance of the valve.

[0273] At the same time, when the artificial valve leaflet bends, the degree of curvature of the surface is greater than that of the interior. Therefore, cracking usually starts from the surface. The surface polyurethane with strong inter-molecular chain forces can delay the occurrence of cracking and improve the fatigue resistance of the valve leaflet.

[0274] Since the thickness of the surface polyurethane is relatively thin, it has little effect on the overall mechanical properties of the film. Therefore, through the combination of the surface polyurethane and the inner polyurethane, the artificial valve leaflet material can have better biostability, biocompatibility, creep resistance, and fatigue resistance without affecting its own fluid properties.

[0275] The surface polyurethane is cross-linked and modified.

[0276] The inner layer of polyurethane is not cross-linked, while the surface layer of polyurethane is cross-linked separately, so that the inner and surface layers of polyurethane exhibit different properties that can cooperate with each other. Specifically, after the surface polyurethane is cross-linked, the interaction force between the molecular chains of the surface polyurethane is greatly increased, reducing the probability of water and oxygen intrusion leading to hydrolysis of the inner layer of polyurethane. The increased interaction force between the molecular chains of the surface polyurethane also limits the occurrence of creep, so that the artificial valve leaflet material has better biostability, biocompatibility, creep resistance, and fatigue resistance. Since the inner layer of polyurethane is not cross-linked, it can still maintain good fluid properties. The properties of the inner and surface polyurethanes cooperate with each other, so that the artificial valve leaflet material ultimately exhibits better biostability, biocompatibility, creep resistance, fatigue resistance and fluid properties.

[0277] The cross-linking modification of the surface polyurethane is carried out by adopting one of radiation cross-linking and chemical cross-linking.

[0278] A valve leaflet is prepared using the artificial valve leaflet material.

[0279] A valve comprising:

[0280] Stent, with a blood flow channel inside;

[0281] One or more leaflets, wherein the leaflets are prepared using the artificial leaflet material.

[0282] A method for preparing an artificial valve leaflet material, comprising:

[0283] Step 1: immerse the mold in the first surface polyurethane solution, wait for a predetermined time, take it out, and dry it at 30-80° C. under an inert gas atmosphere to form a film;

[0284] The above step 1 is performed 1 to 9 times to obtain a first surface layer of the artificial valve leaflet material;

[0285] Step 2: immerse the mold in the inner layer polyurethane solution, take it out after staying for a predetermined time, and dry it at 30-80° C. under an inert gas atmosphere to form a film;

[0286] The above step 2 is performed 1 to 9 times to obtain the inner layer of the artificial valve leaflet material;

[0287] Step 3: Install the petal frame onto the mold, then immerse it in the second surface polyurethane solution, wait for a predetermined time, take it out, and dry it at 30-80° C. under an inert gas atmosphere to form a film;

[0288] The above step 3 is performed 1 to 9 times to obtain a second surface layer of the artificial valve leaflet material;

[0289] Step 4: demoulding by immersion in water to obtain the artificial valve leaflet material.

[0290] In step 1, the first surface layer is formed by repeatedly forming the film 1 to 9 times, with each film forming a corresponding sub-layer, and each sub-layer together constitutes the first surface layer. The process of steps 2 and 3 is explained similarly.

[0291] The contact surfaces of each sub-layer are formed by contact, penetration and solidification of adjacent parts in the form of solution. Since the same material (all polyurethane) is used, the compatibility between the sub-layers is better and the interface bonding force is stronger.

[0292] The first surface polyurethane and the second surface polyurethane may be the same or different. The first surface polyurethane and the second surface polyurethane are both surface polyurethanes.

[0293] The hard segment content of the surface layer polyurethane is 45-60%, and the hard segment content of the inner layer polyurethane is 30-45%.

[0294] The inner layer polyurethane is prepared by using an alcohol chain extender, and the surface layer polyurethane is prepared by using an amine chain extender.

[0295] The alcohol chain extender is at least one of ethylene glycol, propylene glycol, butanediol, pentanediol, hexanediol, octanediol, and 1,3-bis(4-hydroxybutyl)-1,1,3,3-tetramethyldisiloxane (BHTD).

[0296] The amine chain extender is at least one of ethylenediamine, propylenediamine, butylenediamine, pentamethylenediamine, hexamethylenediamine, and octanediamine.

[0297] The concentration of the polyurethane solution of the first surface layer is 10-30 w / v%. The concentration of the polyurethane solution of the second surface layer is 5-15 w / v%.

[0298] The concentration of the inner layer polyurethane solution is 10-30 w / v%.

[0299] The solvent of the first surface layer polyurethane solution, the second surface layer polyurethane solution, and the inner layer polyurethane solution is each one of N,N-dimethylacetamide (DMAc), dimethylformamide (DMF), dimethyl sulfoxide (DMSO), toluene, and tetrahydrofuran (THF).

[0300] In step 1, the drying time is 1 to 6 hours.

[0301] In step 2, the drying time is 1 to 6 hours.

[0302] In step 3, the drying time is 1 to 12 hours.

[0303] In step 1, the predetermined time of staying in the first surface polyurethane solution is 5 to 10 seconds.

[0304] In step 2, the predetermined time of staying in the inner layer polyurethane solution is 5 to 10 seconds.

[0305] In step 3, the predetermined time of staying in the second surface polyurethane solution is 5 to 10 seconds.

[0306] A method for preparing an artificial valve leaflet material, comprising:

[0307] Step 1, preparing a polyurethane film with an elastic modulus of 5 to 30 MPa and a thickness of 80 to 210 microns;

[0308] Step 2: Cover the surface of the film with an isocyanate solution containing a catalyst, and react at 50-90° C. for 3-5 hours to obtain the artificial valve leaflet material.

[0309] The molecular chain structure of polyurethane includes a hard segment and a soft segment, wherein the hard segment includes a first segment formed by isocyanate and a second segment formed by a chain extender;

[0310] The isocyanate is at least one of toluene diisocyanate (TDI), hexamethylene diisocyanate (HDI), diphenylmethane diisocyanate (MDI), naphthalene diisocyanate (NDI), terephthalate diisocyanate (PPDI), isophorone diisocyanate (IPDI), xylylene diisocyanate (XDI), and triphenylmethane triisocyanate;

[0311] The chain extender is at least one of ethylene glycol, propylene glycol, butanediol, pentanediol, hexanediol, octanediol, ethylenediamine, propylenediamine, butanediamine, pentanediamine, hexanediamine, octanediamine, and 1,3-bis(4-hydroxybutyl)-1,1,3,3-tetramethyldisiloxane (BHTD);

[0312] The soft segment raw material is at least one of DONALO T5651, DONALO T5652, polyethylene glycol (PHMO), polytetramethylene glycol (PTMO), adipic acid polyester diol, succinic acid polyester diol and polydimethylsiloxane diol.

[0313] In the molecular chain structure of the polyurethane, the isocyanate is one of diphenylmethane diisocyanate, toluene diisocyanate and hexamethylene diisocyanate.

[0314] In the molecular chain structure of the polyurethane, the isocyanate is diphenylmethane diisocyanate.

[0315] In the molecular chain structure of the polyurethane, the chain extender is at least one of ethylenediamine and 1,3-bis(4-hydroxybutyl)-1,1,3,3-tetramethyldisiloxane.

[0316] In the molecular chain structure of the polyurethane, the chain extender is ethylenediamine and 1,3-bis(4-hydroxybutyl)-1,1,3,3-tetramethyldisiloxane.

[0317] In the molecular chain structure of the polyurethane, the chain extender is ethylenediamine and 1,3-bis(4-hydroxybutyl)-1,1,3,3-tetramethyldisiloxane, and the molar ratio of ethylenediamine to 1,3-bis(4-hydroxybutyl)-1,1,3,3-tetramethyldisiloxane is 1:0.9-1.1.

[0318] In the molecular chain structure of the polyurethane, the soft segment raw material is at least one of polydimethylsiloxane and polyethylene glycol.

[0319] In the molecular chain structure of polyurethane, the soft segment raw materials are polydimethylsiloxane and polyethylene glycol.

[0320] In the molecular chain structure of the polyurethane, the soft segment raw materials are polydimethylsiloxane and polyethylene glycol, and the mass ratio of polydimethylsiloxane to polyethylene glycol is 3 to 6:1.

[0321] The hard segment content of the polyurethane is 30%-60%. The hard segment content of the polyurethane is 35%-60%.

[0322] The isocyanate index of polyurethane is 1.0 to 1.1. The isocyanate index of polyurethane is 1.0 to 1.05. The isocyanate index of polyurethane is 1.0 to 1.02.

[0323] The surface of the film is covered with an isocyanate solution containing a catalyst. The isocyanate in the isocyanate solution reacts with the molecular chains of the polyurethane to form a cross-linked structure. That is, the same isocyanate chemically bonds with the reaction sites of the two polyurethane molecular chains to form a connection structure between the polyurethane molecular chains. The reaction temperature of the isocyanate side chain cross-linking is high and the reaction time is long.

[0324] The film can be prepared in step 1 by using existing techniques, such as dipping, hot pressing, or other forming methods.

[0325] In step 2, the surface of the film is covered with an isocyanate solution containing a catalyst, and the covering method includes at least one of immersion, coating, and spraying.

[0326] In step 2, the surface of the film is covered with an isocyanate solution containing a catalyst, the isocyanate is infiltrated within a range of 5 to 30 microns from the surface of the film, and the heating reaction is used to induce side chain crosslinking.

[0327] Isocyanate solution is infiltrated within a range of 5 to 30 microns from the film surface, and under the action of a catalyst, side chain cross-linking is initiated to form a polyurethane with a different structure from the original structure of the film within a range of 5 to 30 microns from the film surface. The polyurethane with a cross-linked structure is the surface polyurethane, and the original structure of the film inside the surface polyurethane is the inner polyurethane.

[0328] When polyurethane is infiltrated into the film surface, the penetration depth needs to be controlled within the range of 5 to 30 microns from the film surface. The penetration of isocyanate is to use a solvent to swell the polyurethane on the film surface. During the swelling process, the solvent gradually penetrates into the polyurethane molecular chains. The penetration depth is related to the type of solvent and the immersion time. At the same time, during the process of the solvent penetrating into the polyurethane molecular chains, chemical reactions are also taking place. The cross-linking of the surface layer will make the structure of the polyurethane film denser, and it will become increasingly difficult for isocyanate to penetrate deep into the polyurethane film. Therefore, the reaction rate (related to the reaction temperature) will also affect the penetration depth. The penetration depth can be controlled by optimizing the concentration of the solvent and isocyanate solution, the reaction temperature, and the reaction time.

[0329] The surface polyurethane with a cross-linked structure is difficult to dissolve in solvents. The method of first forming a film and then modifying the film surface can avoid the problem of insolubility of the cross-linked polyurethane when multi-layer coating and curing are used to form a film.

[0330] In step 2, the isocyanate in the isocyanate solution is one of HMDI, MDI, and HDI, and the solvent is at least one of cyclohexane, toluene, ethyl acetate, and cyclohexanone.

[0331] In step 2, the concentration of the isocyanate solution is 5 wt.%-20 wt.%.

[0332] After the reaction in step 2 is complete, the artificial valve leaflet material is post-processed. The post-processing includes: washing with an isocyanate solution solvent, washing with ether in sequence under an inert gas atmosphere, and finally drying.

[0333] In step 2, the solvent rinse with isocyanate solution and the ether rinse are mainly used to remove the residual isocyanate on the surface of the polyurethane.

[0334] A method for preparing an artificial valve leaflet material, comprising:

[0335] Step 1, preparing a polyurethane film with an elastic modulus of 5 to 30 MPa and a thickness of 80 to 210 microns;

[0336] Step 2: Cover the surface of the film with an isocyanate solution containing a catalyst and react at 50-90° C. for 1-3 hours;

[0337] Step 3: The product of step 2 is placed in a modifier solution and reacted at 30-50° C. for 12-24 hours to obtain the artificial valve leaflet material.

[0338] The molecular chain structure of polyurethane includes a hard segment and a soft segment, wherein the hard segment includes a first segment formed by isocyanate and a second segment formed by a chain extender;

[0339] The isocyanate is at least one of toluene diisocyanate (TDI), hexamethylene diisocyanate (HDI), diphenylmethane diisocyanate (MDI), naphthalene diisocyanate (NDI), terephthalate diisocyanate (PPDI), isophorone diisocyanate (IPDI), xylylene diisocyanate (XDI), and triphenylmethane triisocyanate;

[0340] The chain extender is at least one of ethylene glycol, propylene glycol, butanediol, pentanediol, hexanediol, octanediol, ethylenediamine, propylenediamine, butanediamine, pentanediamine, hexanediamine, octanediamine, and 1,3-bis(4-hydroxybutyl)-1,1,3,3-tetramethyldisiloxane (BHTD);

[0341] The soft segment raw material is at least one of DONALO T5651, DONALO T5652, polyethylene glycol (PHMO), polytetramethylene glycol (PTMO), adipic acid polyester diol, succinic acid polyester diol and polydimethylsiloxane diol.

[0342] In the molecular chain structure of the polyurethane, the isocyanate is one of diphenylmethane diisocyanate, toluene diisocyanate and hexamethylene diisocyanate.

[0343] In the molecular chain structure of the polyurethane, the isocyanate is diphenylmethane diisocyanate.

[0344] In the molecular chain structure of the polyurethane, the chain extender is at least one of ethylenediamine and 1,3-bis(4-hydroxybutyl)-1,1,3,3-tetramethyldisiloxane.

[0345] In the molecular chain structure of the polyurethane, the chain extender is ethylenediamine and 1,3-bis(4-hydroxybutyl)-1,1,3,3-tetramethyldisiloxane.

[0346] In the molecular chain structure of the polyurethane, the chain extender is ethylenediamine and 1,3-bis(4-hydroxybutyl)-1,1,3,3-tetramethyldisiloxane, and the molar ratio of ethylenediamine to 1,3-bis(4-hydroxybutyl)-1,1,3,3-tetramethyldisiloxane is 1:0.9-1.1.

[0347] In the molecular chain structure of the polyurethane, the soft segment raw material is at least one of polydimethylsiloxane and polyethylene glycol.

[0348] In the molecular chain structure of polyurethane, the soft segment raw materials are polydimethylsiloxane and polyethylene glycol.

[0349] In the molecular chain structure of the polyurethane, the soft segment raw materials are polydimethylsiloxane and polyethylene glycol, and the mass ratio of polydimethylsiloxane to polyethylene glycol is 3 to 6:1.

[0350] The hard segment content of the polyurethane is 30%-60%. The hard segment content of the polyurethane is 35%-60%.

[0351] The isocyanate index of polyurethane is 1.0 to 1.1. The isocyanate index of polyurethane is 1.0 to 1.05. The isocyanate index of polyurethane is 1.0 to 1.02.

[0352] In step 2, the surface of the film is covered with an isocyanate solution containing a catalyst. The isocyanate in the isocyanate solution reacts with the molecular chains of the polyurethane to form a cross-linked structure. That is, the same isocyanate chemically bonds with the reaction sites of the two polyurethane molecular chains to form a connection structure between the polyurethane molecular chains. The reaction temperature of the isocyanate side chain cross-linking is relatively high and the reaction time is relatively long.

[0353] The reaction temperature in step 2 is relatively high. In order to avoid the same type of chemical reaction from continuing to occur in step 3, the reaction temperature is lowered. When the reaction temperature is lowered, the reaction of -OH and -NCO will also slow down. In order to allow the reaction to proceed fully, the reaction time is extended.

[0354] The film can be prepared in step 1 by using existing techniques, such as dipping, hot pressing, or other forming methods.

[0355] In step 2, the film surface is covered with an isocyanate solution containing a catalyst, the isocyanate is infiltrated within a range of 5 to 30 microns from the film surface, and the side chain reaction is initiated by heating to introduce -NCO into the side chain of the polyurethane.

[0356] In step 3, the modification of the polyurethane is completed by grafting the modifier onto the -NCO group. The introduction of the modifier into the polyurethane, on the one hand, limits the mobility of the soft segment due to the steric effect of the side chain, thereby improving the strength and hardness of the polyurethane. At the same time, the side chain tends to be distributed on the surface under the guidance of the lowest energy arrangement. The excellent biostability and biocompatibility of the side chain give the polyurethane biostability and biocompatibility.

[0357] In step 2, the isocyanate in the isocyanate solution is one of HMDI, MDI, and HDI, and the solvent is one of cyclohexane, toluene, ethyl acetate, and cyclohexanone.

[0358] In step 2, the concentration of the isocyanate solution is 5 wt.% to 20 wt.%.

[0359] After the reaction in step 2 is complete, the artificial valve leaflet material is post-processed, which includes: washing with an isocyanate solution solvent and washing with ether in an inert gas atmosphere.

[0360] In step 2, the isocyanate solution solvent rinse and ether rinse are mainly used to remove residual isocyanate on the surface of the polyurethane.

[0361] In step 3, the modifier is one of 3-aminopropyltriethoxysilane, a fluorinated alcohol (e.g., 4-fluorobenzyl alcohol, CAS No. 459-56-3, 1H,1H-perfluorododecan-1-ol, CAS No. 423-65-4), sphingosine phosphocholine (CAS No. 1670-26-4), and 3-((tert-butyldimethylsilyl)oxy)-propanol).

[0362] The solvent of the modifier in step 3 is at least one of cyclohexane, toluene, DMF, DMAc, and DMSO.

[0363] A method for preparing a leaflet, comprising:

[0364] Step 1: immerse the mold in the first surface polyurethane solution, wait for a predetermined time, take it out, and dry it at 30-80° C. under an inert gas atmosphere to form a film;

[0365] The above step 1 is performed 1 to 9 times to obtain a first surface layer of the artificial valve leaflet material;

[0366] Step 2: immerse the mold in the inner layer polyurethane solution, take it out after staying for a predetermined time, and dry it at 30-80° C. under an inert gas atmosphere to form a film;

[0367] The above step 2 is performed 1 to 9 times to obtain the inner layer of the artificial valve leaflet material;

[0368] Step 3: Cut into leaflet shapes and install the leaflet frame on the mold;

[0369] Step 4, then immersing it in the second surface polyurethane solution, taking it out after staying for a predetermined time, and drying it at 30-80° C. under an inert gas atmosphere to form a film;

[0370] The above step 4 is performed 1 to 9 times to obtain a second surface layer of the artificial valve leaflet material;

[0371] Step 5: Demolding by soaking in water to obtain the petals.

[0372] A method for preparing a valve, comprising:

[0373] Step 1: immerse the mold in the first surface polyurethane solution, wait for a predetermined time, take it out, and dry it at 30-80° C. under an inert gas atmosphere to form a film;

[0374] The above step 1 is performed 1 to 9 times to obtain a first surface layer of the artificial valve leaflet material;

[0375] Step 2: immerse the mold in the inner layer polyurethane solution, take it out after staying for a predetermined time, and dry it at 30-80° C. under an inert gas atmosphere to form a film;

[0376] The above step 2 is performed 1 to 9 times to obtain the inner layer of the artificial valve leaflet material;

[0377] Step 3: Cut into leaflet shapes and install the leaflet frame on the mold;

[0378] Step 4, then immersing it in the second surface polyurethane solution, taking it out after staying for a predetermined time, and drying it at 30-80° C. under an inert gas atmosphere to form a film;

[0379] The above step 4 is performed 1 to 9 times to obtain a second surface layer of the artificial valve leaflet material;

[0380] Step 5: soaking in water and demoulding to obtain the valve.

[0381] Example 1: Introduction of isocyanate into the side chain and blocking with a modifier

[0382] A method for preparing an artificial valve leaflet comprises the following steps:

[0383] (1) A biocompatible polyurethane was prepared, wherein the polyurethane composition included 44 wt.% PDMS, 11 wt.% PHMO, 31.6 wt.% MDI, 3.2 wt.% BDO, and 10.2 wt.% BHTD.

[0384] (2) Using dimethylacetamide (DMAc) as solvent, 20 wt.% and 10 wt.% polyurethane solutions were prepared respectively.

[0385] (3) Slowly immerse the mold into a 20 wt.% polyurethane solution for 5 seconds.

[0386] (4) Dry the mold at 60°C under nitrogen atmosphere for 3 h.

[0387] (5) Repeat steps (3) and (4) six times.

[0388] (6) Put the petal frame onto the mold (see FIG9 , put the petal frame 2 onto the mold 1 ), and immerse the mold with the petal frame into a 10 wt.% polyurethane solution for 5 seconds.

[0389] (7) Dry at 60°C under nitrogen atmosphere for 6 h.

[0390] (8) Trim the leaflets, then immerse the mold in water for 4 hours and demold (the polyurethane separates from the mold after immersion in water, making demolding easy).

[0391] (9) A cyclohexane solution of diphenylmethane-4,4'-diisocyanate (MDI) was prepared to form a 10 (w / v)% cyclohexane solution.

[0392] (10) Under a nitrogen atmosphere, the leaflets were immersed in a cyclohexane solution containing MDI and reacted at 70°C for 2 h (the reaction mechanism is shown below). The leaflet surface was rinsed with cyclohexane solvent and ether in turn to remove residual isocyanate. The leaflets were stored in a dry nitrogen atmosphere until use.

[0393] (11) 3-aminopropyltriethoxysilane was dissolved in dimethylformamide (DMF) to prepare a 5 (w / v)% 3-aminopropyltriethoxysilane solution.

[0394] (12) The leaflets were immersed in 3-aminopropyltriethoxysilane solution and reacted at 40 °C for 12 h. The surface was rinsed several times with the solvent and with deionized water.

[0395] (13) The leaflet thickness is 0.19 mm.

[0396] Example 2 Chain extenders are different

[0397] A method for preparing an artificial valve leaflet comprises the following steps:

[0398] (1) preparing a surface polyurethane, wherein the surface polyurethane comprises 44 wt.% PDMS, 11 wt.% PHMO, 39.2 wt.% MDI, 5.8 wt.% EDA,

[0399] (2) Preparing an inner layer polyurethane, the components of the inner layer polyurethane include 44wt.% PDMS, 11wt.% PHMO, 37wt.% MDI, and 8.0wt.% BDO

[0400] (3) Prepare 20 wt.% inner layer polyurethane solution (using DMAc as solvent), 20 wt.% surface layer polyurethane solution (using DMAc as solvent), and 10 wt.% surface layer polyurethane solution (using DMAc as solvent).

[0401] (4) Slowly immerse the mold into a 20 wt.% surface polyurethane solution for 5 seconds.

[0402] (5) Dry the mold at 60°C under nitrogen atmosphere for 3 h.

[0403] (6) Slowly immerse the mold into the 20 wt.% inner layer polyurethane solution for 5 seconds.

[0404] (7) Dry the mold at 60°C under nitrogen atmosphere for 3 h.

[0405] (8) Repeat steps (6) and (7) four times.

[0406] (9) Put the petal frame onto the mold, and immerse the mold with the petal frame into a 10 wt.% surface polyurethane solution for 5 seconds.

[0407] (10) Dry at 60°C under nitrogen atmosphere for 6 h.

[0408] (11) Trim the petals, then immerse the mold in water for 4 hours and demold.

[0409] The process of this embodiment is simple. On the basis of the original material system, the chain extender used in the surface polyurethane is adjusted, the urea content in the surface polyurethane material is increased, and the biostability, biocompatibility, creep resistance and durability of the leaflet are greatly improved.

[0410] (12) The leaflet thickness is 0.18 mm.

[0411] Example 3: Different soft and hard segment contents

[0412] A method for preparing an artificial valve leaflet comprises the following steps:

[0413] (1) Prepare a surface polyurethane, the components of which include 44 wt.% PDMS, 11 wt.% PHMO, 32.3 wt.% MDI, 2.3 wt.% EDA, and 10.40 wt.% BHTD.

[0414] (2) Prepare an inner layer polyurethane, the components of which include 46.4 wt.% PDMS, 11.6 wt.% PHMO, 30.7 wt.% MDI, 2.0 wt.% EDA, and 9.3 wt.% BHTD.

[0415] (3) Prepare 20 wt.% inner layer polyurethane solution (using DMAc as solvent), 20 wt.% surface layer polyurethane solution (using DMAc as solvent), and 10 wt.% surface layer polyurethane solution (using DMAc as solvent).

[0416] (4) Slowly immerse the mold into a 20 wt.% surface polyurethane solution for 5 seconds.

[0417] (5) Dry the mold at 60°C under nitrogen atmosphere for 3 h.

[0418] (6) Slowly immerse the mold into the 20 wt.% inner layer polyurethane solution for 5 seconds.

[0419] (7) Dry the mold at 60°C under nitrogen atmosphere for 3 h.

[0420] (8) Repeat steps (6) and (7) four times.

[0421] (9) Put the petal frame onto the mold, and immerse the mold with the petal frame into a 10 wt.% surface polyurethane solution for 5 seconds.

[0422] (10) Dry at 60°C under nitrogen atmosphere for 6 h.

[0423] (11) Trim the petals, then immerse the mold in water for 4 hours and demold.

[0424] (12) The leaflet thickness is 0.18 mm.

[0425] Example 4 Surface cross-linking

[0426] A method for preparing an artificial valve leaflet comprises the following steps:

[0427] (1) A biocompatible polyurethane was prepared, wherein the polyurethane composition included 44 wt.% PDMS, 11 wt.% PHMO, 31.6 wt.% MDI, 3.2 wt.% BDO, and 10.2 wt.% BHTD.

[0428] (2) Prepare 20 wt.% polyurethane solution (using DMAc as solvent) and 10 wt.% polyurethane solution (using DMAc as solvent).

[0429] (3) Slowly immerse the mold into a 20 wt.% polyurethane solution for 5 seconds.

[0430] (4) Dry the mold at 60°C under nitrogen atmosphere for 3 h.

[0431] (5) Repeat steps (3) and (4) six times.

[0432] (6) Put the valve frame onto the mold, and immerse the mold with the valve frame into a 10 wt.% polyurethane solution for 5 seconds.

[0433] (7) Dry at 60°C under nitrogen atmosphere for 6 h.

[0434] (8) Trim the petals, then immerse the mold in water for 4 hours and demold.

[0435] (9) A cyclohexane solution of diphenylmethane-4,4'-diisocyanate (MDI) was prepared to form a 10 (w / v)% cyclohexane solution.

[0436] (10) Under nitrogen atmosphere, the leaflets were immersed in a cyclohexane solution containing MDI and reacted at 70 °C for 4 h. The surface was rinsed several times with the solvent and several times with deionized water.

[0437] (11) The leaflet surface thickness is 0.17 mm.

[0438] Example 5 Different chain extenders

[0439] A method for preparing an artificial valve leaflet comprises the following steps:

[0440] (1) Prepare a surface polyurethane, the composition of which includes 44 wt.% PDMS, 11 wt.% PHMO, 39.2 wt.% HDI, and 5.8 wt.% EDA.

[0441] (2) An inner layer polyurethane was prepared, wherein the components of the inner layer polyurethane included 44 wt.% PDMS, 11 wt.% PHMO, 37.0 wt.% HDI, and 8.0 wt.% BDO.

[0442] (3) Prepare 20 wt.% inner layer polyurethane solution (using DMAc as solvent), 20 wt.% surface layer polyurethane solution (using DMAc as solvent), and 10 wt.% surface layer polyurethane solution (using DMAc as solvent).

[0443] (4) Slowly immerse the mold into a 20 wt.% surface polyurethane solution for 5 seconds.

[0444] (5) Dry the mold at 60°C under nitrogen atmosphere for 3 h.

[0445] (6) Slowly immerse the mold into the 20 wt.% inner layer polyurethane solution for 5 seconds.

[0446] (7) Dry the mold at 60°C under nitrogen atmosphere for 3 h.

[0447] (8) Repeat steps (6) and (7) four times.

[0448] (9) Put the petal frame onto the mold, and immerse the mold with the petal frame into a 10 wt.% surface polyurethane solution for 5 seconds.

[0449] (10) Dry at 60°C under nitrogen atmosphere for 6 h.

[0450] (11) Trim the petals, then immerse the mold in water for 4 hours and demold.

[0451] (12) The leaflet thickness is 0.18 mm.

[0452] The process of this embodiment is simple. On the basis of the original material system, the chain extender used in the surface polyurethane is adjusted, the urea content in the surface polyurethane material is increased, and the biostability, biocompatibility, creep resistance and durability of the leaflet are greatly improved.

[0453] Example 6 Different chain extenders

[0454] A method for preparing an artificial valve leaflet comprises the following steps:

[0455] (1) Prepare a surface polyurethane, wherein the surface polyurethane comprises 5 wt.% PDMS, 50 wt.% Durain T5651, 39.2 wt.% MDI, and 5.8 wt.% EDA.

[0456] (2) An inner layer polyurethane was prepared, wherein the components of the inner layer polyurethane included 5 wt.% PDMS, 50 wt.% Durain T5651, 37.0 wt.% MDI, and 8.0 wt.% BDO.

[0457] (3) Prepare 20 wt.% inner layer polyurethane solution (using DMAc as solvent), 20 wt.% surface layer polyurethane solution (using DMAc as solvent), and 10 wt.% surface layer polyurethane solution (using DMAc as solvent).

[0458] (4) Slowly immerse the mold into a 20 wt.% surface polyurethane solution for 5 seconds.

[0459] (5) Dry the mold at 60°C under nitrogen atmosphere for 3 h.

[0460] (6) Slowly immerse the mold into the 20 wt.% inner layer polyurethane solution for 5 seconds.

[0461] (7) Dry the mold at 60°C under nitrogen atmosphere for 3 h.

[0462] (8) Repeat steps (6) and (7) four times.

[0463] (9) Put the petal frame onto the mold, and immerse the mold with the petal frame into a 10 wt.% surface polyurethane solution for 5 seconds.

[0464] (10) Dry at 60°C under nitrogen atmosphere for 6 h.

[0465] (11) Trim the petals, then immerse the mold in water for 4 hours and demold.

[0466] (12) The leaflet thickness is 0.18 mm.

[0467] The process of this embodiment is simple. On the basis of the original material system, the chain extender used in the surface polyurethane is adjusted, the urea content in the surface polyurethane material is increased, and the biostability, biocompatibility, creep resistance and durability of the leaflet are greatly improved.

[0468] Example 7: The surface layer is provided with two sub-layers

[0469] A method for preparing an artificial valve leaflet comprises the following steps:

[0470] (1) Prepare the first sub-layer polyurethane of the surface layer, wherein the components of the surface polyurethane include 5wt.% PDMS, 50wt.% Durain T5651, 39.2wt.% MDI, and 5.8wt.% EDA.

[0471] (2) Prepare the second sub-layer polyurethane of the surface layer, the components of the surface polyurethane include 4.4wt.% PDMS, 44wt.% Durain T5651, 44.8wt.% MDI, and 6.8wt.% EDA.

[0472] (3) An inner layer polyurethane was prepared, wherein the components of the inner layer polyurethane included 5 wt.% PDMS, 50 wt.% Durain T5651, 37.0 wt.% MDI, and 8.0 wt.% BDO.

[0473] (4) Prepare 20wt.% inner layer polyurethane solution (using DMAc as solvent), 8wt.% surface first sub-layer polyurethane solution (using DMAc as solvent), 8wt.% surface second sub-layer polyurethane solution (using DMAc as solvent), 15wt.% surface first sub-layer polyurethane solution (using DMAc as solvent), and 15wt.% surface second sub-layer polyurethane solution (using DMAc as solvent).

[0474] (5) Slowly immerse the mold into the 15 wt.% surface second sub-layer polyurethane solution for 5 seconds.

[0475] (6) Dry the mold at 60°C under nitrogen atmosphere for 3 h.

[0476] (7) Slowly immerse the mold into the 15 wt.% surface first sub-layer polyurethane solution for 5 seconds.

[0477] (8) Dry the mold at 60°C under nitrogen atmosphere for 3 h.

[0478] (9) Slowly immerse the mold into the 20 wt.% inner layer polyurethane solution for 5 seconds.

[0479] (10) Dry the mold at 60°C under nitrogen atmosphere for 3 h.

[0480] (11) Repeat steps (9) and (10) four times.

[0481] (12) Put the petal frame onto the mold, and immerse the mold with the petal frame into 8 wt.% surface first sub-layer polyurethane solution for 5 seconds.

[0482] (13) Dry the mold at 60°C under nitrogen atmosphere for 3 h.

[0483] (14) Immerse the mold with the valve frame into 8 wt.% surface second sub-layer polyurethane solution for 5 seconds.

[0484] (15) Dry the mold at 60 °C under nitrogen atmosphere for 6 h.

[0485] (16) Trim the petals, then immerse the mold in water for 4 hours and demold.

[0486] (17) The leaflet thickness is 0.18 mm.

[0487] Comparative Example 1

[0488] A method for preparing an artificial valve leaflet comprises the following steps:

[0489] (1) A polyurethane was prepared, wherein the polyurethane composition included 44 wt.% PDMS, 11 wt.% PHMO, 32.3 wt.% MDI, 2.3 wt.% EDA, and 10.40 wt.% BHTD.

[0490] (2) Prepare 20 wt.% polyurethane solution (using DMAc as solvent) and 10 wt.% polyurethane solution (using DMAc as solvent).

[0491] (3) Slowly immerse the mold into 18 wt.% polyurethane solution for 5 seconds.

[0492] (4) Dry the mold at 60°C under nitrogen atmosphere for 3 h.

[0493] (5) Repeat steps (3) and (4) five times.

[0494] (6) Put the valve frame onto the mold, and immerse the mold with the valve frame into 8 wt.% polyurethane solution for 5 seconds.

[0495] (7) Dry at 60°C under nitrogen atmosphere for 6 h.

[0496] (8) Trim the petals, then immerse the mold in water for 4 hours and demold.

[0497] (9) The leaflet thickness is 0.18 mm.

[0498] Comparative Example 2

[0499] A method for preparing an artificial valve leaflet comprises the following steps:

[0500] (1) A polyurethane was prepared, wherein the polyurethane composition included 44 wt.% PDMS, 11 wt.% PHMO, 31.6 wt.% MDI, 3.2 wt.% BDO, and 10.2 wt.% BHTD.

[0501] (2) Prepare 20 wt.% polyurethane solution (using DMAc as solvent) and 10 wt.% polyurethane solution (using DMAc as solvent).

[0502] (3) Slowly immerse the mold into a 22 wt.% polyurethane solution for 5 seconds.

[0503] (4) Dry the mold at 60°C under nitrogen atmosphere for 3 h.

[0504] (5) Repeat steps (3) and (4) five times.

[0505] (6) Put the valve frame onto the mold, and immerse the mold with the valve frame into a 10 wt.% polyurethane solution for 5 seconds.

[0506] (7) Dry at 60°C under nitrogen atmosphere for 6 h.

[0507] (8) Trim the petals, then immerse the mold in water for 4 hours and demold.

[0508] (9) The leaflet thickness is 0.18 mm.

[0509] Performance Characterization

[0510] The performance characterization results of Examples 1 to 7 and Comparative Examples 1 to 2 are shown in Table 1.

[0511] Table 1

[0512] The test methods for hydrolysis resistance and oxidation resistance are as follows:

[0513] The leaflet material was stored at 37°C in a 20wt.% H2O2, 0.1mol / L CoCl2, pH=5.0±0.2 solution with a strain of 150% for 90 days. If the surface morphology did not change significantly, it had excellent oxidation resistance. The excellent oxidation resistance also reflected biological stability to a certain extent. The good oxidation resistance means that defects are not easily generated on the material surface, and fatigue resistance can be guaranteed to a certain extent.

[0514] In Example 1, isocyanate was introduced into the polyurethane side chain on the leaflet surface and capped with a modifier, thereby achieving leaflet surface modification. From the results of the oxidation resistance test, the surface of Example 1 (Figure 1) was smooth and free of oxidation marks, while Comparative Example 1 (Figure 8) without surface modification had a relatively large number of cracks. This indicates that the method of introducing isocyanate into the polyurethane side chain on the leaflet surface and capping with a modifier can significantly improve the biostability of the leaflet, while fatigue performance is also greatly improved. This is related to the fact that the surface is not prone to defects after surface modification. In contrast, there was no significant change in the transvalvular pressure difference and EOA, which proves that surface modification has almost no effect on the fluid performance of the leaflet.

[0515] In Example 2, Example 5, and Example 6, polyurethane materials with different chain extenders are used in the surface and inner layers. Amines are added to the surface polyurethane as chain extenders to enhance the interaction between the hard segment and the soft segment, making the overall structure denser. While improving its own biological stability, it can also have a protective effect on the inner layer. Moreover, due to the enhancement of the interaction between the hard segment and the soft segment, the mobility of the soft segment is weakened, and the ability to transport water and oxygen to the interior is weakened, further protecting the inner layer of polyurethane. The results of the oxidation resistance test show that the surfaces of Example 2 (Figure 2), Example 5 (Figure 5), and Example 6 (Figure 6) are smooth and have no obvious cracks, which indicates that their surface oxidation resistance is greatly improved, and their surface is not prone to defects, which in turn greatly improves fatigue performance. In contrast, there is no significant change in the transvalvular pressure difference and EOA. This surface-distributed surface polyurethane has almost no effect on the fluid performance of the leaflet.

[0516] Example 3 uses polyurethane with a higher hard segment content in the surface polyurethane. The higher the hard segment content, the more hard segment force is applied to the unit soft segment, the denser the whole is, the improved biostability itself, the weaker the mobility of the soft segment, the weakened ability to transport water and oxygen to the interior, and the protection of the inner layer of polyurethane. At the same time, since the main reason for the oxidative attack of polyurethane is the soft segment, the higher the proportion of hard segments, the better the biostability, which further improves the biostability of the surface. Tiny cracks appear on the surface of Example 3 (Figure 3), but the cracks are much shallower than those on the surface of Comparative Example 1, which proves that the biostability of the leaflet is greatly improved, and its surface is not prone to defects, which in turn greatly improves fatigue performance. In contrast, there is no significant change in the transvalvular pressure difference and EOA, and the surface polyurethane distributed on the surface has almost no effect on the fluid properties of the leaflet.

[0517] In Example 4, the surface of the polyurethane is cross-linked and modified. The cross-linked polyurethane forms chemical bonds between the molecular chains. The relative movement between the soft segment molecules is more restricted, the overall appearance is denser, and the biological stability itself is improved. The weaker the mobility of the soft segment, the weaker the ability to transport water and oxygen to the interior, thereby achieving the effect of protecting the inner layer of polyurethane. The surface of Example 4 (Figure 4) is smooth and defect-free compared to Comparative Example 1 (Figure 8), which proves that the biological stability of the leaflet is greatly improved. Its surface is not prone to defects, which in turn greatly improves fatigue performance. In contrast, there is no significant change in the transvalvular pressure difference and EOA. The surface polyurethane distributed on the surface has almost no effect on the fluid performance of the leaflet.

[0518] Comparative Example 2 uses materials with a higher elastic modulus as a whole. From the results of the oxidation resistance test, its surface is very smooth, so the overall biostability and creep resistance are significantly improved. However, due to its overall hardening, the fluid performance is significantly reduced.

[0519] The technical features of the above-mentioned embodiments can be combined arbitrarily. In order to make the description concise, not all possible combinations of the technical features in the above-mentioned embodiments are described. However, as long as there is no contradiction in the combination of these technical features, they should be considered to be within the scope of this specification.

[0520] 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 present invention. It should be noted that a person skilled in the art could make various modifications and improvements without departing from the spirit of the present application, all of which fall within the scope of protection of the present application. Therefore, the scope of protection of the present patent application shall be determined by the appended claims.

Claims

1. An artificial valve leaflet material, characterized in that: include: The artificial valve leaflet material is made of polyurethane and comprises an inner layer and surface layers located at two opposite sides of the inner layer in the thickness direction. The elastic modulus of the surface layer polyurethane is greater than the elastic modulus of the inner layer polyurethane.

2. The artificial valve leaflet material according to claim 1, characterized in that: The elastic modulus of the surface polyurethane is 10 to 60 MPa greater than the elastic modulus of the inner polyurethane.

3. The artificial valve leaflet material according to claim 1, characterized in that: The elastic modulus of the surface polyurethane is 30 to 100 MPa.

4. The artificial valve leaflet material according to claim 1, characterized in that: The elastic modulus of the inner layer polyurethane is 5 to 30 MPa.

5. The artificial valve leaflet material according to claim 1, characterized in that: Oxygen permeability of surface polyurethane ≤9*10 9 (cm 2 / sec*cm*Hg).

6. The artificial valve leaflet material according to claim 1, characterized in that: The molecular chain structure of the surface polyurethane and the inner polyurethane meets at least one of the following conditions: a. The hard segment content of the inner layer polyurethane material is less than that of the surface layer polyurethane; b. The inner layer polyurethane is prepared using an alcohol chain extender, and the surface layer polyurethane is prepared using an amine chain extender; c. The surface polyurethane has a higher degree of cross-linking than the inner polyurethane.

7. The artificial valve leaflet material according to claim 1, characterized in that: The molecular chain structure of the surface polyurethane includes a hard segment and a soft segment, wherein the hard segment includes a first segment formed by isocyanate and a second segment formed by a chain extender; The isocyanate is at least one of toluene diisocyanate (TDI), hexamethylene diisocyanate (HDI), diphenylmethane diisocyanate (MDI), naphthalene diisocyanate (NDI), terephthalene diisocyanate (PPDI), isophorone diisocyanate (IPDI), xylylene diisocyanate (XDI), and triphenylmethane triisocyanate; The chain extender is at least one of ethylene glycol, propylene glycol, butanediol, pentanediol, hexanediol, octanediol, ethylenediamine, propylenediamine, butanediamine, pentanediamine, hexanediamine, octanediamine, and 1,3-bis(4-hydroxybutyl)-1,1,3,3-tetramethyldisiloxane (BHTD); The soft segment raw material is at least one of DONALO T5651, DONALO T5652, polyethylene glycol (PHMO), polytetramethylene glycol (PTMO), adipic acid polyester diol, succinic acid polyester diol and polydimethylsiloxane diol.

8. The artificial valve leaflet material according to claim 7, characterized in that: In the molecular chain structure of the surface polyurethane, the isocyanate is one of diphenylmethane diisocyanate, toluene diisocyanate and hexamethylene diisocyanate.

9. The artificial valve leaflet material according to claim 7, characterized in that: In the molecular chain structure of the surface polyurethane, the isocyanate is diphenylmethane diisocyanate.

10. The artificial valve leaflet material according to claim 7, characterized in that: In the molecular chain structure of the surface polyurethane, the chain extender is at least one of ethylenediamine and 1,3-bis(4-hydroxybutyl)-1,1,3,3-tetramethyldisiloxane.

11. The artificial valve leaflet material according to claim 7, characterized in that: In the molecular chain structure of the surface polyurethane, the chain extender is ethylenediamine and 1,3-bis(4-hydroxybutyl)-1,1,3,3-tetramethyldisiloxane.

12. The artificial valve leaflet material according to claim 7, characterized in that: In the molecular chain structure of the surface polyurethane, the chain extender is ethylenediamine and 1,3-bis(4-hydroxybutyl)-1,1,3,3-tetramethyldisiloxane, and the molar ratio of ethylenediamine to 1,3-bis(4-hydroxybutyl)-1,1,3,3-tetramethyldisiloxane is 1:0.9-1.

1.

13. The artificial valve leaflet material according to claim 7, characterized in that: In the molecular chain structure of the surface polyurethane, the soft segment raw material is at least one of polydimethylsiloxane and polyethylene glycol.

14. The artificial valve leaflet material according to claim 7, characterized in that: In the molecular chain structure of the surface polyurethane, the soft segment raw materials are polydimethylsiloxane and polyethylene glycol.

15. The artificial valve leaflet material according to claim 7, characterized in that: In the molecular chain structure of the surface polyurethane, the soft segment raw materials are polydimethylsiloxane and polyethylene glycol, and the mass ratio of polydimethylsiloxane to polyethylene glycol is 3 to 6:

1.

16. The artificial valve leaflet material according to claim 1, characterized in that: The molecular chain structure of the inner layer polyurethane includes a hard segment and a soft segment, wherein the hard segment includes a first segment formed by isocyanate and a second segment formed by a chain extender; The isocyanate is at least one of toluene diisocyanate (TDI), hexamethylene diisocyanate (HDI), diphenylmethane diisocyanate (MDI), naphthalene diisocyanate (NDI), terephthalene diisocyanate (PPDI), isophorone diisocyanate (IPDI), xylylene diisocyanate (XDI), and triphenylmethane triisocyanate; Chain extenders include ethylene glycol, propylene glycol, butanediol, pentanediol, hexanediol, octanediol, ethylenediamine, propylenediamine, butanediol At least one of amine, pentamethylenediamine, hexamethylenediamine, octanediamine, and 1,3-bis(4-hydroxybutyl)-1,1,3,3-tetramethyldisiloxane (BHTD); The soft segment raw material is at least one of DONALO T5651, DONALO T5652, polyethylene glycol (PHMO), polytetramethylene glycol (PTMO), adipic acid polyester diol, succinic acid polyester diol and polydimethylsiloxane diol.

17. The artificial valve leaflet material according to claim 16, characterized in that: In the molecular chain structure of the inner layer polyurethane, the isocyanate is one of diphenylmethane diisocyanate, toluene diisocyanate and hexamethylene diisocyanate.

18. The artificial valve leaflet material according to claim 16, characterized in that: In the molecular chain structure of the inner layer polyurethane, the isocyanate is diphenylmethane diisocyanate.

19. The artificial valve leaflet material according to claim 16, characterized in that: In the molecular chain structure of the inner layer polyurethane, the chain extender is at least one of ethylenediamine and 1,3-bis(4-hydroxybutyl)-1,1,3,3-tetramethyldisiloxane.

20. The artificial valve leaflet material according to claim 16, characterized in that: In the molecular chain structure of the inner layer polyurethane, the chain extender is ethylenediamine and 1,3-bis(4-hydroxybutyl)-1,1,3,3-tetramethyldisiloxane.

21. The artificial valve leaflet material according to claim 16, characterized in that: In the molecular chain structure of the inner layer polyurethane, the chain extender is ethylenediamine and 1,3-bis(4-hydroxybutyl)-1,1,3,3-tetramethyldisiloxane, and the molar ratio of ethylenediamine to 1,3-bis(4-hydroxybutyl)-1,1,3,3-tetramethyldisiloxane is 1:0.9-1.

1.

22. The artificial valve leaflet material according to claim 16, characterized in that: In the molecular chain structure of the inner layer polyurethane, the soft segment raw material is at least one of polydimethylsiloxane and polyethylene glycol.

23. The artificial valve leaflet material according to claim 16, characterized in that: In the molecular chain structure of the inner layer polyurethane, the soft segment raw materials are polydimethylsiloxane and polyethylene glycol.

24. The artificial valve leaflet material according to claim 16, characterized in that: In the molecular chain structure of the inner layer polyurethane, the soft segment raw materials are polydimethylsiloxane and polyethylene glycol, and the mass ratio of polydimethylsiloxane to polyethylene glycol is 3 to 6:

1.

25. The artificial valve leaflet material according to claim 1, characterized in that: The hard segment content of the surface polyurethane and the inner polyurethane is 30%-60%.

26. The artificial valve leaflet material according to claim 1, characterized in that: The hard segment content of the surface polyurethane and the inner polyurethane is 35% to 60%.

27. The artificial valve leaflet material according to claim 1, characterized in that: The isocyanate index of the surface polyurethane and the inner polyurethane is 1.0 to 1.

1.

28. The artificial valve leaflet material according to claim 1, characterized in that: The isocyanate index of the surface polyurethane and the inner polyurethane is 1.0 to 1.

05.

29. The artificial valve leaflet material according to claim 1, characterized in that: The isocyanate index of the surface polyurethane and the inner polyurethane is 1.0 to 1.

02.

30. The artificial valve leaflet material according to claim 1, characterized in that: The thickness of the artificial valve leaflet material is 75 to 210 microns.

31. The artificial valve leaflet material according to claim 1, characterized in that: The thickness of the artificial valve leaflet material is 80 to 210 microns.

32. The artificial valve leaflet material according to claim 1, characterized in that: The thickness of the inner layer polyurethane is 70 to 170 microns, and the thickness of the surface layer polyurethane is 5 to 40 microns.

33. The artificial valve leaflet material according to claim 1, characterized in that: The thickness of the inner layer polyurethane is 70 to 170 microns, and the thickness of the surface layer polyurethane is 10 to 40 microns.

34. The artificial valve leaflet material according to claim 1, characterized in that: The thickness of the inner layer polyurethane is 70 to 150 microns, and the thickness of the surface layer polyurethane is 5 to 30 microns.

35. The artificial valve leaflet material according to claim 1, characterized in that: The inner layer includes at least one first sublayer along the thickness direction, each first sublayer adopts the same type of polyurethane, or the elastic modulus of each first sublayer increases gradually from the inside to the outside in the thickness direction at intervals of a predetermined value.

36. The artificial valve leaflet material according to claim 35, characterized in that: The elastic modulus of each first sub-layer gradually increases by 5 to 10 MPa.

37. The artificial valve leaflet material according to claim 1, characterized in that: The inner layer includes 1 to 6 first sublayers, each first sublayer is divided into at least two groups, each first sublayer in the same group has the same elastic modulus, and the elastic modulus of each group of first sublayers increases gradually from inside to outside in the thickness direction at intervals of a predetermined value.

38. The artificial valve leaflet material according to claim 1, characterized in that: The surface layer includes at least one second sublayer along the thickness direction, each second sublayer adopts the same type of polyurethane, or the elastic modulus of each second sublayer increases gradually from the inside to the outside in the thickness direction at intervals of a predetermined value.

39. The artificial valve leaflet material according to claim 38, characterized in that: The elastic modulus of each second sub-layer gradually increases by 5 to 10 MPa.

40. The artificial valve leaflet material according to claim 1, characterized in that: The surface layer includes 2 to 4 second sublayers, each second sublayer is divided into at least two groups, the second sublayers in the same group have the same elastic modulus, and the elastic modulus of each group of second sublayers increases gradually from inside to outside in the thickness direction at intervals of a predetermined value.

41. The artificial valve leaflet material according to claim 1, characterized in that: The hard segment content of the inner layer polyurethane is less than that of the surface layer polyurethane.

42. The artificial valve leaflet material according to claim 41, characterized in that: The hard segment content of the surface layer polyurethane is 45-60%, and the hard segment content of the inner layer polyurethane is 30-45%.

43. The artificial valve leaflet material according to claim 1, characterized in that: The hard segments in the molecular chain structure of the surface polyurethane and the inner polyurethane are modified in one of the following ways: A. Introducing fluorinated side chains; B. Introduce a chain extender containing POSS groups.

44. The artificial valve leaflet material according to claim 43, characterized in that: The introduction of fluorinated side chains is achieved by: Add 3% to 10% by mass of fluorinated diisocyanate to the synthetic raw materials of polyurethane.

45. The artificial valve leaflet material according to claim 43, characterized in that: The introduction of POSS groups is achieved by: The chain extender diol having a POSS group is added in an amount of 1% to 3% by mass to the synthetic raw materials of the polyurethane.

46. ​​The artificial valve leaflet material according to claim 1, characterized in that: The inner layer polyurethane is prepared by using an alcohol chain extender, and the surface layer polyurethane is prepared by using an amine chain extender.

47. The artificial valve leaflet material according to claim 46, characterized in that: The alcohol chain extender is at least one of ethylene glycol, propylene glycol, butylene glycol, pentanediol, hexanediol, octanediol, and 1,3-bis(4-hydroxybutyl)-1,1,3,3-tetramethyldisiloxane (BHTD).

48. The artificial valve leaflet material according to claim 46, characterized in that: The amine chain extender is at least one of ethylenediamine, propylenediamine, butylenediamine, pentylenediamine, hexylenediamine and octanediamine.

49. The artificial valve leaflet material according to claim 46, characterized in that: The alcohol chain extender is butanediol.

50. The artificial valve leaflet material according to claim 46, characterized in that: The amine chain extender is ethylenediamine.

51. The artificial valve leaflet material according to claim 46, characterized in that: The alcohol chain extender is butanediol, and the amine chain extender is ethylenediamine.

52. The artificial valve leaflet material according to claim 1, characterized in that: The surface polyurethane is cross-linked and modified.

53. The artificial valve leaflet material according to claim 52, characterized in that: The cross-linking modification of the surface polyurethane is carried out by radiation cross-linking or chemical cross-linking.

54. A valve leaflet, characterized in that: It is prepared using the artificial valve leaflet material described in any one of claims 1 to 53.

55. A valve, characterized in that: include: The stent has a blood flow channel inside; One or more valve leaflets, wherein the valve leaflets are prepared using the artificial valve leaflet material described in any one of claims 1 to 53.

56. A method for preparing an artificial valve leaflet material according to any one of claims 1 to 53, characterized in that: include: Step 1, immersing the mold in the first surface polyurethane solution, taking it out after staying for a predetermined time, and drying it at 30-80° C. under an inert gas atmosphere to form a film; The above step 1 is performed 1 to 9 times to obtain a first surface layer of the artificial valve leaflet material; Step 2, immersing the mold in the inner layer polyurethane solution, taking it out after staying for a predetermined time, and drying it at 30-80° C. under an inert gas atmosphere to form a film; The above step 2 is performed 1 to 9 times to obtain the inner layer of the artificial valve leaflet material; Step 3, installing the valve frame on the mold, then immersing it in the second surface polyurethane solution, taking it out after staying for a predetermined time, and drying it at 30-80° C. under an inert gas atmosphere to form a film; The above step 3 is performed 1 to 9 times to obtain a second surface layer of the artificial valve leaflet material; Step 4, demoulding by immersion in water to obtain the artificial valve leaflet material.

57. The method for preparing an artificial valve leaflet material according to claim 56, characterized in that: The concentration of the polyurethane solution of the first surface layer is 10-30 w / v%. The concentration of the polyurethane solution of the second surface layer is 5-15 w / v%.

58. The method for preparing an artificial valve leaflet material according to claim 56, characterized in that: The concentration of the inner layer polyurethane solution is 10-30 w / v%.

59. The method for preparing an artificial valve leaflet material according to claim 56, characterized in that: The solvents of the first surface layer polyurethane solution, the second surface layer polyurethane solution and the inner layer polyurethane solution are each one of N,N-dimethylacetamide (DMAc), dimethylformamide (DMF), dimethyl sulfoxide (DMSO), toluene and tetrahydrofuran (THF).

60. The method for preparing an artificial valve leaflet material according to claim 56, characterized in that: In step 1, the drying time is 1 to 6 hours.

61. The method for preparing an artificial valve leaflet material according to claim 56, characterized in that: In step 1, the predetermined time of staying in the first surface polyurethane solution is 5 to 10 seconds.

62. The method for preparing an artificial valve leaflet material according to claim 56, characterized in that: In step 2, the predetermined time of staying in the inner layer polyurethane solution is 5 to 10 seconds.

63. The method for preparing an artificial valve leaflet material according to claim 56, characterized in that: In step 3, the predetermined time of staying in the second surface polyurethane solution is 5 to 10 seconds.

64. A method for preparing an artificial valve leaflet material according to any one of claims 1 to 53, characterized in that: include: Step 1, preparing a polyurethane film with an elastic modulus of 5 to 30 MPa and a thickness of 80 to 210 microns; Step 2, covering the surface of the film with an isocyanate solution containing a catalyst, reacting at 50-90° C. for 3-5 hours to obtain the artificial valve leaflet material.

65. The method for preparing an artificial valve leaflet material according to claim 64, characterized in that: In step 2, the surface of the film is covered with an isocyanate solution containing a catalyst, and the covering method includes at least one of immersion, coating, and spraying.

66. The method for preparing an artificial valve leaflet material according to claim 64, characterized in that: In step 2, the surface of the film is covered with an isocyanate solution containing a catalyst, isocyanate is infiltrated within a range of 5 to 30 microns from the surface of the film, and a heating reaction is performed to induce side chain crosslinking.

67. The method for preparing an artificial valve leaflet material according to claim 64, characterized in that: In step 2, the isocyanate in the isocyanate solution is one of HMDI, MDI, and HDI, and the solvent is at least one of cyclohexane, toluene, ethyl acetate, and cyclohexanone.

68. The method for preparing an artificial valve leaflet material according to claim 64, characterized in that: In step 2, the concentration of the isocyanate solution is 5wt.%-20wt.%.

69. A method for preparing an artificial valve leaflet material according to any one of claims 1 to 53, characterized in that: include: Step 1, preparing a polyurethane film with an elastic modulus of 5 to 30 MPa and a thickness of 80 to 210 microns; Step 2, covering the surface of the film with an isocyanate solution containing a catalyst, and reacting at 50 to 90° C. for 1 to 3 hours; Step 3, the product of step 2 is placed in a modifier solution, and reacted at 30-50° C. for 12-24 hours to obtain the artificial valve leaflet material.

70. The method for preparing an artificial valve leaflet material according to claim 69, characterized in that: In step 2, the isocyanate in the isocyanate solution is one of HMDI, MDI, and HDI, and the solvent is one of cyclohexane, toluene, ethyl acetate, and cyclohexanone.

71. The method for preparing an artificial valve leaflet material according to claim 69, characterized in that: In step 2, the concentration of the isocyanate solution is 5 wt.% to 20 wt.%.

72. The method for preparing an artificial valve leaflet material according to claim 69, characterized in that: In step 3, the modifier is one of 3-aminopropyltriethoxysilane, fluorinated alcohol, sphingosine phosphorylcholine, and 3-((tert-butyldimethylsilyl)oxy)-propanol.

73. The method for preparing an artificial valve leaflet material according to claim 69, characterized in that: The solvent of the modifier in step 3 is at least one of cyclohexane, toluene, DMF, DMAc, and DMSO.

74. A method for preparing a leaflet as claimed in claim 54, characterized in that: include: Step 1, immersing the mold in the first surface polyurethane solution, taking it out after staying for a predetermined time, and drying it at 30-80° C. under an inert gas atmosphere to form a film; The above step 1 is performed 1 to 9 times to obtain a first surface layer of the artificial valve leaflet material; Step 2, immersing the mold in the inner layer polyurethane solution, taking it out after staying for a predetermined time, and drying it at 30-80° C. under an inert gas atmosphere to form a film; The above step 2 is performed 1 to 9 times to obtain the inner layer of the artificial valve leaflet material; Step 3, cutting into the shape of the petal leaf, and installing the petal frame on the mold; Step 4, then immersing it in the second surface polyurethane solution, taking it out after staying for a predetermined time, and drying it at 30-80° C. under an inert gas atmosphere to form a film; The above step 4 is performed 1 to 9 times to obtain a second surface layer of the artificial valve leaflet material; Step 5, demoulding by soaking in water to obtain the petal.

75. A method for preparing the valve according to claim 55, characterized in that: include: Step 1, immersing the mold in the first surface polyurethane solution, taking it out after staying for a predetermined time, and drying it at 30-80° C. under an inert gas atmosphere to form a film; The above step 1 is performed 1 to 9 times to obtain a first surface layer of the artificial valve leaflet material; Step 2, immersing the mold in the inner layer polyurethane solution, taking it out after staying for a predetermined time, and drying it at 30-80° C. under an inert gas atmosphere to form a film; The above step 2 is performed 1 to 9 times to obtain the inner layer of the artificial valve leaflet material; Step 3, cutting into the shape of the petal leaf, and installing the petal frame on the mold; Step 4, then immersing it in the second surface polyurethane solution, taking it out after staying for a predetermined time, and drying it at 30-80° C. under an inert gas atmosphere to form a film; The above step 4 is performed 1 to 9 times to obtain a second surface layer of the artificial valve leaflet material; Step 5, demoulding by soaking in water to obtain the valve.

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