Polyurethane urea thermoplastic elastomer composite material

Abstract

The invention relates to a copolymer chain segment as shown in a formula I and a polyurethane urea thermoplastic elastomer composite material which comprises the copolymer chain segment as shown in the formula I and a divalent compound (such as diisocyanate), a chain extender and polysiloxane glycol. Also disclosed herein are methods of producing the copolymer segments of Formula I, and possible uses of the composites in forming biomaterials for articles, including medical devices, such as implants, heart valves, and drug delivery devices.

Description

TECHNICAL FIELD

[0001] The present application belongs to the technical field of polymer synthesis and biomedical materials, and particularly relates to a polyurethane urea thermoplastic elastomer composite material and a preparation method thereof. More particularly, the present application provides a block copolymer segment based on specific soft segment structure design, which is formed by the synergistic reaction of a diisocyanate compound, a chain extender, and a polyol amine macromolecular / supramolecular polymer, to form an elastomer material with an optimized phase separation structure. The material system is particularly suitable for manufacturing biomedical devices such as implantable medical devices, artificial organs, and controlled-release drug delivery systems. BACKGROUND

[0002] With the development of biomedical engineering, there is an increasing demand for elastomer materials with excellent mechanical properties and biocompatibility. Thermoplastic polyurethane and its derivative polyurea have been widely used in the field of medical devices such as cardiovascular stents, artificial heart valves, and artificial skin due to their adjustable soft and hard segment ratio and good processing performance. However, traditional polyurethane and polyurea materials have the following technical bottlenecks: (1) incomplete phase separation: the high thermodynamic compatibility between conventional polyol soft segments (such as polyether / polyester type) and hard segments leads to insufficient microphase separation, directly affecting the creep resistance and long-term stability of the material; (2) lack of biological activity: the existing polyurethane material has a limited range of surface energy adjustment, making it difficult to achieve specific interaction with biological tissues, which can easily lead to fibrous capsule formation and calcification after implantation; (3) insufficient mechanical adaptability: polyurea materials have higher hardness, but their elongation at break is usually less than 300%, which cannot meet the dynamic mechanical requirements of flexible implants such as artificial heart valves; (4) ordinary composite materials are new materials constructed by physical combination of two or more materials. Materials constructed by physical combination are prone to porosity / bubble, delamination (poor interlayer bonding), uneven fiber distribution, inclusions, and other defects during manufacturing, and are prone to impact damage, surface delamination or matrix cracking, fatigue damage, gradual debonding of fiber-matrix interface under cyclic loading, and environmental aging and thermal residual stress during use.

[0003] Chinese patent CN108290992A describes a polyurethane urea material with excellent properties, good mechanical properties and biological properties. However, after the valve is formed, the material punching appears stress concentration phenomenon, resulting in significant decrease in physical properties. In order to meet the urgent demand for implantable elastomer materials in the biomedical field, it is of great significance to develop a thermoplastic polyurethane-polyurea synthetic composite material with adjustable ratio of two hard segments (urea bond and urethane) and more excellent mechanical and biological properties.

[0004] The disclosure relates to chemically linked macromolecular diols, macromolecular diamines, and macromolecular diols and amines with chain length control, and containing one or more chemically distinct moieties within the polymer backbone. These chain length controlled macromolecular diols and diamines can be used to formulate polyurethane-polyureas for biomedical and non-biomedical applications. SUMMARY

[0005] In view of the above, the present application provides a polyurethane urea thermoplastic elastomer composite material, which has excellent mechanical adjustable performance and biological performance, so as to meet the urgent needs of modern biomedical field for implant elastomer materials.

[0006] To achieve the above object, the present application adopts the following technical scheme: A copolymer segment having a structure shown in Formula I: ; wherein A1, A2 are independently selected from hydrogen, hydroxyl or amino; The monomer of B1 is selected from diol, diamine or alcohol amine; The monomer of B2 is selected from alcohol amine; The diol is selected from siloxane diol, alkane diol, carbonate diol or ester diol; The diamine is selected from siloxane diamine, alkane diamine, carbonate diamine or ester diamine; The alcohol amine is selected from siloxane alcohol amine, alkane alcohol amine, carbonate alcohol amine or ester alcohol amine; The monomer of C1, C2 is independently selected from alkane dihalogen compound, ether dihalogen compound, aromatic dihalogen compound, ester dihalogen compound or siloxane dihalogen compound; The substituent group D in the present application 1 , D 2 is a divalent linking group containing the following groups: urea linking group -NH-CO-NH- and / or carbamate group -NH-COO-, and the monomer is diisocyanate.

[0007] The carbamate linking group can be generated by reacting a hydroxyl-containing compound with diisocyanate. The urea linking group can be generated by reacting an amine-containing compound (e.g., a macromolecular diamine) with diisocyanate.

[0008] Examples of suitable diisocyanates include aliphatic, cyclic or aromatic diisocyanates, such as 1,4-diisocyanatobutane, 1,12-diisocyanatododecane, 1,6-diisocyanatohexane, 1,8-diisocyanatooctane, 4,4'- methylenedi-phenyl diisocyanate (MDI), 4,4'-methylenebis(cyclohexyl diisocyanate) (H12MDI), p-phenylene diisocyanate (p-PDI), m-phenylene diisocyanate (m-PDI), trans- cyclohexane-1,4-diisocyanate (CHDI), or a mixture of cis and trans isomers, 1,6- hexamethylene diisocyanate (HDI), 2,4-toluene diisocyanate (2,4-TDI) or its isomer (e.g. 2,6-toluene diisocyanate (2,6-TDI)), or mixtures thereof, p-tetramethylxylene diisocyanate (p-TMXDI), isophorone diisocyanate or m-tetramethylxylene diisocyanate (m-TMXDI), or 1,5- diisocyanatobenzene (NDI).

[0009] m is selected from an integer from 1 to 10; n is selected from an integer from 0 to 10; E is a moiety of Formula A or Formula B;

[0010] wherein R2, R3, R5 and R6 are each independently selected from hydrogen or an optionally substituted linear, branched or cyclic, saturated and unsaturated C1-C6 hydrocarbyl group; R1 and R4 are each independently selected from a linear, branched or cyclic, saturated and unsaturated hydrocarbylene group, optionally interrupted by one or more heteroatoms independently selected from O, N and S; x is an integer from 1 to 50;

[0011] wherein R7 and R8 are each independently selected from a linear, branched or cyclic, saturated or unsaturated hydrocarbylene group, a monocyclic, polycyclic or fused ring, carbocyclic and heterocyclic, substituted or unsubstituted aromatic group; y is an integer from 1 to 60; z is an integer from 1 to 60.

[0012] As a preference, the siloxane diol is a dimethylsiloxane diol, the siloxane diamine is a dimethylsiloxane diamine, and the siloxane diol amine is a dimethylsiloxane diol amine; As a preference, the alkane diol, alkane diamine, alkane diol amine, are each independently selected from a C2-C20 linear, branched or cyclic, saturated and unsaturated hydrocarbyl diol, diamine or diol amine; As a preference, the carbonate diols, carbonate diamines, carbonate diol amines are independently selected from linear, branched or cyclic, saturated and unsaturated C2-C20 carbonate diols, diamines or diol amines. As a preference, the ester diols, ester diamines, ester diol amines are independently selected from linear, branched or cyclic, saturated and unsaturated C2-C20 ester diols, diamines or diol amines.

[0013] The present application further provides a polyurethane urea composite material comprising the following monomers: at least one copolymer segment of Formula I, a diisocyanate, a polysiloxane diol, and one or more chain extenders.

[0014] As a preference, the diisocyanate is selected from 1,4-diisocyanatobutane, 1,12-diisocyanatododecane, 1,6-diisocyanatohexane, 1,8-diisocyanatooctane, 4,4'-methylene diphenyl diisocyanate, 4,4'-methylenebis(cyclohexyl) diisocyanate, p-phenylene diisocyanate, m-phenylene diisocyanate, trans-cyclohexane-1,4-diisocyanate or a mixture of cis and trans isomers, 1,6-hexylene diisocyanate, 2,4-toluene diisocyanate, 2,6-toluene diisocyanate, p-tetramethyl xylene diisocyanate, isophorone diisocyanate and m-tetramethyl xylene diisocyanate, 1,6-diisocyanatohexane, 1,3-bis(1-isocyanato-1-methylethyl) benzene and 1,5-diisocyanatonaphthalene.

[0015] As a preference, the at least one chain extender is selected from C1-12 alkane diols, C1-12 alkane diamines and C1-12 alkane diol amines.

[0016] As a more preference, the at least one chain extender is selected from 1,4-butanediol, 1,6-hexanediol, 1,8-octanediol, 1,9-nonanediol, 1,10-decanediol 1,4-cyclohexanedimethanol, p-xyleneglycol, 1,4-bis(2-hydroxyethoxy)benzene, 1,12-dodecanediol, 1,3 bis-(4-hydroxybutyl) 1,1,3,3-tetramethyldisiloxane, 1,2-ethanediamine, ethanolamine, 1,4-butanediamine, 1,3-propanediamine, 1,3 bis-(3-aminopropyl) tetramethyldisiloxane and 1,3 bis-(3-aminobutyl) tetramethyldisiloxane.

[0017] The present application also provides a medical device consisting entirely or partially of the polyurethane or polyurethane urea elastomeric material of the present application.

[0018] The medical device is selected from cardiac pacemakers, defibrillators, catheters, heart valves, cardiac assist devices, artificial blood vessels, implantable prostheses, cannulas, external devices, artificial organs, pacemaker leads, defibrillator leads, blood pumps, balloon pumps, arteriovenous shunts, biosensors, cell encapsulation membranes, drug delivery devices, wound dressings, artificial joints, orthopedic implants, and soft tissue substitutes. A heart valve is preferred.

[0019] The present invention also provides a method for preparing the composite material, which involves using the Formula I segment, adding diisocyanate, reacting with polysiloxane diol, and then adding a chain extender to extend the chain.

[0020] The present invention also provides a method for preparing a heart valve, using the aforementioned composite material, employing a spin coater, and performing a homogenization operation, a film spinning operation, and a drying operation; subsequently repeating the above operations continuously until a polymer film is obtained, and shaping the film into the shape and size of a heart valve.

[0021] the term Regarding the definitions provided herein, unless otherwise stated or implied by the context, the defined terms and wording include the meanings provided. Unless otherwise clearly stated or obvious from the context, the following terms and wording do not exclude the meaning of the terms or wording as would be understood by one of skill in the art. Definitions are provided to aid in describing particular embodiments and are not intended to limit the claimed invention, as the scope of the invention is limited only by the claims. Furthermore, unless the context requires otherwise, singular terms shall include plural terms, and plural terms shall include singular terms.

[0022] In this invention, the term "polyurethane" refers to a polymer chain comprising a urethane (-NH-COO-) bond containing a linking monomer or "macromonomer" unit. Polyurethane can be produced by reacting a molecule containing at least two isocyanate functional groups with other molecules containing at least two alcohol groups (hydroxyl groups).

[0023] In this invention, the term "polyurea" refers to a polymer chain containing urea bonds (-NH-CO-NH-) linking monomer or "macromonomer" units. Polyureas can be produced by reacting molecules containing at least two isocyanate groups with other molecules containing at least two amine groups.

[0024] In this invention, the term "polyurethane urea" refers to a polymer chain containing both urethane and urea linking groups.

[0025] In this invention, the term "macromolecular diol with chain length regulated" refers to a polymer material containing two hydroxyl groups generated by the polymerization reaction of small diol molecules of different chain lengths with small dihalogen molecules, and the chain length is a calculated value. The term "macromolecular diamine with chain length regulated" refers to a polymer material containing two amino groups generated by the polymerization reaction of small diamine molecules of different chain lengths with small dihalogen molecules, and the chain length is a calculated value. The term "macromolecular diolamine with chain length regulated" refers to a polymer material containing one amino group and one hydroxyl group generated by the polymerization reaction of small diolamine molecules of different chain lengths with small dihalogen molecules, and the chain length is a calculated value. The term "macromonomer" refers to a polymer having at least one polymerizable group (e.g., hydroxyl group) capable of reacting with another compound (e.g., diisocyanate).

[0026] In this specification, aspects and components of the invention may be listed in scope form. Scope forms are included for convenience and should not be construed as rigid limitations on the scope of the invention. Therefore, the description of scopes should be considered as specifically disclosing all possible sub-scopes and individual numerical values ​​within those scopes, unless otherwise specifically indicated. For example, describing a scope such as 1-5 should be considered as specifically disclosing sub-scopes such as 1-3, 1-4, 1-5, 2-4, 2-5, 3-5, etc., and individual values ​​and fractional values ​​(unless integers are required) within the cited scope, such as 1, 2, 3, 4, 5, 5.5, and 6. This applies to other scopes, regardless of the width of the disclosed scope. Where specific values ​​are required, these will be indicated in this specification.

[0027] In this invention, the term "hydrocarbon group" refers to a substituted straight-chain, branched, or cyclic, saturated or unsaturated hydrocarbon group.

[0028] The term "alkyl" refers to a straight-chain, branched, or monocyclic or polycyclic alkyl group, such as C10. 1-18 Alkyl or C 3-8 Cycloalkyl. For example, "C 1-18 "alkyl" and "C" 3-8 "Cycloalkyl" refers to an alkyl group having 1-18 carbon atoms or a cycloalkyl group having 3-8 carbon atoms.

[0029] Those skilled in the art will understand that the term "C" 1-18"Alkyl" refers to an alkyl group having 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, or 18 carbon atoms, or a range containing any two of these integers and including 1-2, 1-3, 1-4, 1-5, 1-6, 1-7, 1-8, 1-9, 1-10, 1-11, 1-12, 1-13, 1-14, 1-15, 1-16, 1-17, or 1-18 carbon atoms. Examples of straight-chain and branched alkyl groups include optionally substituted ones: methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, pentyl, isopentyl, sec-pentyl, 1,2-dimethylpropyl, 1,1-dimethylpropyl, pentyl, hexyl, hexyl, 4-methylpentyl, 1-methylpentyl, 2-methylpentyl, 3-methylpentyl, 1 1-Dimethylbutyl, 2,2-Dimethylbutyl, 3,3-Dimethylbutyl, 1,2-Dimethylbutyl, 1,3-Diethylbutyl, 1,2,2-Trimethylpropyl, or 1,1,2-Trimethylpropyl, heptyl, 5-methylhexyl, 1-methylhexyl, 2,2-Dimethylpentyl, 3,3-Dimethylpentyl, 4,4-Dimethylpentyl, 1,2-Dimethylpentyl, 1,3-Dimethylpentyl, 1,4-Dimethylpentyl, 1,2,3-Trimethylbutyl, 1,1,2-Trimethylbutyl, 1,1,3-Trimethylbutyl, octyl, 6-Methylheptyl, 1-Methylheptyl, and 1,1,3,3-Tetramethylbutyl, nonyl, 1-,2-,3- ,4-,5-,6- or 7-methyloctyl, 1-,2-,3-,4- or 5-ethylheptyl, 1-,2- or 3-propylhexyl, decyl, 1-,2-,3-,4-,5-,6-,7- or 8-methylnonyl, 1-,2-,3-,4-,5- or 6-ethyloctyl, 1-,2-,3- or 4-propylheptyl, undecyl, 1-,2-,3-,4-,5-,6-,7-,8- or 9-methyldecyl, 1-,2-,3-,4-,5-,6- or 7-ethylnonyl, 1-,2-,3-,4- or 5-propyloctyl, 1-,2- or 3-butylheptyl, 1-pentylhexyl, dodecyl, 1-,2-,3- ,4-,5-,6-,7-,8-,9- or 10-methylundecyl, 1-,2-,3-,4-,5-,6-,7- or 8-ethyldecyl, 1-,2-,3-,4-,5- or 6-propylnonyl, 1-,2-,3- or 4-butyloctyl, 1-,2-pentylheptyl, tridecyl, tetradecyl, pentadecyl, hexadecyl, heptadecanyl or octadecyl.

[0030] Those skilled in the art will understand that the term "C" 3-8"Cycloalkyl" refers to a cycloalkyl group having 3, 4, 5, 6, 7, or 8 carbon atoms, or a range containing any two of these integers and including 3-4, 3-5, 3-6, 3-7, 3-8, 4-5, 4-6, 4-7, 4-8, 5-6, 5-7, 5-8, 6-7, 6-8, or 7-8 carbon atoms. Examples of cycloalkyl groups include optionally substituted cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, or cyclooctyl.

[0031] The term "alkenyl" refers to a group formed from a straight-chain, branched, monocyclic or polycyclic olefin containing the alkene bond as defined above, such as C 2-18 alkenyl or C 3-8 Cycloalkenyl. "C" 2-18 "Alkenyl" or "C" 3-8 "Cycloalkenyl" refers to alkenyl or cycloalkenyl groups having 2-18 carbon atoms or 3-8 carbon atoms, respectively.

[0032] Those skilled in the art will understand that the term "C" 2-18 "Alkenyl" refers to an alkenyl group having 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, or 18 carbon atoms, or a range containing any two of these integers, and including alkenyl groups with 2-3, 2-4, 2-5, 2-6, 2-7, 2-8, 2-9, 2-10, 2-11, 2-12, 2-13, 2-14, 2-15, 2-16, 2-17, or 2-18 carbon atoms. Those skilled in the art will understand that the term "C"... 3-8 "Cycloalkenyl" refers to a cycloalkenyl group having 3, 4, 5, 6, 7, or 8 carbon atoms, or a range containing any two of these integers and including 3-4, 3-5, 3-6, 3-7, 3-8, 4-5, 4-6, 4-7, 4-8, 5-6, 5-7, 5-8, 6-7, 6-8, or 7-8 carbon atoms. Examples of alkenyl and cycloalkenyl groups include optionally substituted: vinyl, allyl, 1-methylvinyl, butenyl, isobutenyl, 3-methyl-2-butenyl, 1-pentenyl, cyclopentenyl, 1-methyl-cyclopentenyl, 1-hexenyl, 3-hexenyl, cyclohexenyl, 1-heptenyl, 3-heptenyl, 1-octenyl, cyclooctenyl, 1,3-butadienyl, 1,4-pentadienyl, 1,3-cyclopentadienyl, 1 ,3-hexadienyl, 1,4-hexadienyl, 1,3-cyclohexadienyl, 1,4-cyclohexadienyl, 1,3-cycloheptadienyl, 1,3,5-cycloheptadienyl and 1,3,5,7-cyclooctatetraenyl.

[0033] The term "alkynyl" refers to a group formed from straight-chain, branched, or monocyclic or polycyclic alkynes, such as C. 2-18 alkynyl or C 3-8Cycloalkynyl. Examples of alkynyl groups include optionally substituted ones: ethynyl, 1-propynyl, 1- and 2-butynyl, 2-methyl-2-propynyl, 2-pentynyl, 3-pentynyl, 4-pentynyl, 2-hexynyl, 3-hexynyl, 4-hexynyl, 5-hexynyl, 10-undecynyl, 4-ethyl-1-octyyn-3-yl, 7-dodecynyl, 9-dodecynyl, 10-dodecynyl, 3-methyl-2-dodecyn-3-yl, 2-tetrazynyl, 11-tetrazynyl, 3-tetradecynyl, 7-heptadecynyl, and 3-octadecynyl.

[0034] The term "aryl" refers to a single, polynuclear, conjugated, and fused aromatic hydrocarbon residue. Examples of aryl groups include optionally substituted ones: phenyl, biphenyl, terphenyl, tetraphenyl, phenoxyphenyl, naphthyl, tetrahydronaphthyl, anthracel, dihydroanthrayl, benzoanthrayl, dibenzoanthrayl, and phenanthryl.

[0035] The term "heterocyclic group" refers to a monocyclic or polycyclic heterocyclic group containing at least one heteroatom selected from nitrogen, sulfur, and oxygen. Suitable heterocyclic groups include optionally substituted: N-containing heterocyclic groups, such as unsaturated 3-6 membered heterocyclic groups containing 1-4 nitrogen atoms, such as pyrroloyl, pyrrolinyl, imidazolyl, pyrazolyl, pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, triazolyl, or tetrazolyl; saturated 3-6 membered heterocyclic groups containing 1-4 nitrogen atoms, such as pyrrolidinyl, imidazolyl, piperidinyl, or piperazinyl; unsaturated condensed heterocyclic groups containing 1-5 nitrogen atoms, such as indolyl, isoyindolyl, dihydroindolyl, benzimidazolyl, quinolinyl, isoquinolinyl, indolyl, benzotriazolyl, or tetrazolpyridazinyl; unsaturated 3-6 membered heterocyclic groups containing oxygen atoms, such as pyranyl or furanyl; unsaturated 3-6 membered heterocyclic groups containing 1-2 sulfur atoms, for example... Examples include thiophene groups; unsaturated 3-6 membered heterocyclic groups containing 1-2 oxygen atoms and 1-3 nitrogen atoms, such as oxazolyl, isoxazolyl, or oxadiazolyl; saturated 3-6 membered heterocyclic groups containing 1-2 oxygen atoms and 1-3 nitrogen atoms, such as morpholino; unsaturated condensed heterocyclic groups containing 1-2 oxygen atoms and 1-3 nitrogen atoms, such as benzoxazolyl or benzodiazolyl; unsaturated 3-6 membered heterocyclic groups containing 1-2 sulfur atoms and 1-3 nitrogen atoms, such as thiazolyl or thiadiazolyl; saturated 3-6 membered heterocyclic groups containing 1-2 sulfur atoms and 1-3 nitrogen atoms, such as thiadiazolyl; and unsaturated condensed heterocyclic groups containing 1-2 sulfur atoms and 1-3 nitrogen atoms, such as benzothiazolyl or benzothiadiazolyl.

[0036] In this invention, "optionally substituted" means that it may or may not be further substituted by one or more groups selected from the following: oxygen, nitrogen, sulfur, alkyl, alkenyl, alkynyl, aryl, halogen, haloalkyl, haloalkenyl, haloalkynyl, haloaryl, hydroxyl, alkoxy, alkenyloxy, alkynyloxy, aryloxy, carboxyl, benzyloxy, haloalkoxy, haloalkenyloxy, haloalkynyloxy, haloaryloxy, nitro, nitroalkyl, nitroalkenyl, nitroalkynyl, nitroaryl, nitroheterocyclic, azide The following groups are included: alkylamino, alkenylamino, alkynylamino, arylamino, benzylamino, acyl, alkenyl acyl, alkynyl acyl, aryl acyl, acylamino, acyloxy, aldehyde, alkylsulfonyl, arylsulfonyl, alkylsulfonylamino, arylsulfonylamino, alkylsulfonyloxy, arylsulfonyloxy, heterocyclic, heterocyclic oxy, heterocyclic amino, halogenated heterocyclic, alkylsulfinyl, arylcyclosulfinyl, alkoxycarbonyl, aryloxycarbonyl, mercapto, alkylthio, arylthio, or acylthio. It should be understood that the term "optionally substituted" may also be referred to as "substituted or unsubstituted".

[0037] The molecular weight of the block copolymer segments of Formula I according to any of the embodiments described above can be about 400-6000, or about 400-4000, or about 800-1600. Unless otherwise stated, the term "molecular weight" in this invention refers to the number average molecular weight (Mn) of a particular polymer.

[0038] These tensile strengths can be measured using standard industrial methods, such as methods adapted from ASTM standard methods for thin plastic sheets (e.g., ASTM D882-02). In a further example, the method may involve films, for example, about 200-300 micrometers, tested using the ASTM D 882-02 method.

[0039] Examples of conditions under which tensile strength can be measured using the ASTM D 882-02 method are: (1) Use a dumbbell-shaped sample with a length of 75 mm, a width of 13 mm at each end, and a width of 4 mm at the narrowest part in the center (with a constant width over a length of at least 15 mm); and (2) Use an Instron 5565 equipped with a static load pool of ±100N and calibrated with Instron Bluehill 2 (version 2.35) software.

[0040] For tensile tests under dry conditions, the sample can be: (1) Fix the upper and lower clamps (e.g., Instron clamps) so that the gap between the clamps is 10 mm; (2) Stretch a 10 mm section of the membrane at a rate of 50 mm / min until the membrane breaks; (3) Perform at least three repetitions, such as three, four or five repetitions.

[0041] In this invention, the polydispersity index (PDI) of the thermoplastic polyurethane-polyurethane urea elastomer material can be ≤3.00. For example, the PDI of the thermoplastic polyurethane-polyurethane urea elastomer material can be ≤2.50, ≤2.00, or ≤1.50.

[0042] In one embodiment, a single block copolymer segment of Formula I is used in the formulation of the thermoplastic polyurethane-polyurethane urea elastomer material.

[0043] In another embodiment, two different block copolymer segments of Formula I are used in the formulation of the thermoplastic polyurethane-polyurethane urea elastomer material.

[0044] diisocyanate Examples of suitable diisocyanates include, but are not limited to, aliphatic, cyclic, or aromatic diisocyanates, such as 1,4-diisocyanate butane, 1,12-diisocyanate dodecane, 1,6-diisocyanate hexane, 1,8-diisocyanate octane, 4,4′-methylene diphenyl diisocyanate (MDI), 4,4′-methylene bis(cyclohexyl diisocyanate) (H12MDI), p-phenylene diisocyanate (p-PDI), m-phenylene diisocyanate (m-PDI), and trans-cyclohexane-1,4 -Diisocyanate (CHDI), or a mixture of cis and trans isomers, 1,6-hexanediisocyanate (HDI), 2,4-toluenediisocyanate (2,4-TDI) or its isomers (e.g., 2,6-toluenediisocyanate (2,6-TDI)), or mixtures thereof, p-tetramethylxylenediisocyanate (p-TMXDI), isophorone diisocyanate or m-tetramethylxylenediisocyanate (m-TMXDI), or 1,5-diisocyanate naphthalene (NDI).

[0045] In one embodiment, the diisocyanate is MDI.

[0046] Chain extender The formation of thermoplastic polyurethane-polyurethane urea elastomer materials includes at least one chain extender as described in this invention. The chain extender is a chain extender having two functional groups per molecule that can react with the isocyanate group, such as a diol, diamine, or diolamine.

[0047] The molecular weight of the chain extender can be less than or equal to 400. Alternatively, the molecular weight of the chain extender can be from about 800 to about 1600. In another embodiment, the molecular weight of the chain extender can be from about 400 to about 4000.

[0048] The chain extender may be selected from diols, diamines, or diolamine chain extenders. In one embodiment, at least one chain extender is a diol.

[0049] Examples of diol chain extenders include, but are not limited to, C1-12 alkyldiols, such as: 1,4-butanediol, 1,6-hexanediol, 1,8-octanediol, 1,9-nonanediol and 1,10-decanediol, 1,4-cyclohexanediol, p-xylene glycol, 1,4-bis(2-hydroxyethoxy)benzene, 1,12-dodecanediol and 1,3-bis-(4-hydroxybutyl)1,1,3,3-tetramethyldisiloxane.

[0050] In one embodiment, at least one chain extender is a diamine. Suitable diamine chain extenders include C1-12 alkyl diamines, such as 1,2-ethylenediamine, 1,3-propanediamine, 1,4-butanediamine, 1,3-bis-(3-aminopropyl)tetramethyldisiloxane, or 1,3-bis-(3-aminobutyl)tetramethyldisiloxane.

[0051] The range of hard segments within thermoplastic polyurethane-polyurethane urea (wt% (determined by the percentage of the weight of the linking compound (e.g., diisocyanate) + chain extender) relative to the total weight of polyurethane / polyurethane urea) can be about 20-60 wt%. Examples include: about 30-60 wt%, or about 40-60 wt%, about 50-60 wt%, and about 40-50 wt%.

[0052] In one embodiment, only one chain extender is used in the formation of the thermoplastic polyurethane-polyurethane urea elastomer material.

[0053] In one embodiment, two chain extenders are used in the formation of thermoplastic polyurethane or polyurethane urea elastomer materials.

[0054] The "post-perforation attenuation" mentioned in this invention specifically refers to the reduction in the mechanical properties of a material after perforation. Since the sutures are most susceptible to damage after a heart valve is sutured to a stent, this invention focuses on testing the attenuation of the mechanical properties of the thin-film material after perforation.

[0055] Products used for medical applications.

[0056] Thermoplastic polyurethane or polyurethane urea elastomer materials as defined herein can be used as biomaterials. The term "biomaterial" is used in its broadest sense and refers to materials used in situations where they come into contact with the cells and / or bodily fluids of living animals or humans.

[0057] This document discloses an article of manufacture that is a medical device, comprising wholly or partially of a thermoplastic polyurethane-polyurethane urea elastomer material as defined herein. In one embodiment, the article of manufacture as a medical device is an implant.

[0058] Examples of medical devices include: pacemakers, defibrillators, catheters, heart valves, cardiac assist devices, artificial blood vessels, implantable prostheses, cannulas, external devices, artificial organs, pacemaker leads, defibrillator leads, blood pumps, balloon pumps, arteriovenous shunts, biosensors, cell encapsulation membranes, drug delivery devices, wound dressings, artificial joints, orthopedic implants, or soft tissue substitutes.

[0059] In one embodiment, the article is a medical device used in cardiovascular applications, such as an article involving one or more of the following: aortic valve, mitral valve, pulmonary valve, and / or tricuspid valve.

[0060] The thermoplastic polyurethane-polyurethane urea elastomer materials used in the manufacture of medical devices herein should be acceptable for use on or within a recipient (e.g., a human). For example, the thermoplastic polyurethane-polyurethane urea elastomer material should be able to contact the recipient's tissues without excessive toxicity, irritation, allergic reactions, or other potential complications, in accordance with a reasonable benefit / risk ratio determined by a skilled medical professional or veterinarian.

[0061] It should be understood that in some cases, the thermoplastic polyurethane-polyurethane urea elastomer materials described herein may not be used on or within a recipient (e.g., a human), but may be used in the preparation of thermoplastic polyurethane-polyurethane urea elastomer materials that are acceptable for use in medical devices.

[0062] The recipient of the medical device described in this article may be a human being, male or female.

[0063] Alternatively, the recipient of the medical device described herein may be a non-human animal. “Non-human animals” or “non-human animals” means the animal kingdom excluding humans, and includes both male and female vertebrates and invertebrates, including warm-blooded animals, including mammals (including but not limited to primates, dogs, cats, cattle, pigs, sheep, goats, mice, guinea pigs, horses, or other species of the Bovidae, Capricornae, Equidae, Canidae, Felidae, Rodentia, or Muridae families), birds, insects, reptiles, fish, and amphibians.

[0064] The recipient of the medical device described herein is referred to in this invention along with the interchangeable terms “patient,” “recipient,” “individual,” and “experimental subject.” These four terms are used interchangeably and refer to any human or non-human animal as defined herein (unless otherwise specified).

[0065] Compared with the prior art, the advantages of the present invention are: 1. The material of the present invention exhibits minimal mechanical property degradation after perforation, making it less prone to damage when used as a heart valve and sutured onto a stent.

[0066] 2. The material of the present invention has low cytotoxicity, which is conducive to the adhesion and growth of epithelial cells, thereby solving the problem of easy calcification of heart valves in the prior art. Attached Figure Description

[0067] The above and / or additional aspects and advantages of the present invention will become apparent and readily understood from the description of the embodiments taken in conjunction with the following drawings, in which: Figure 1 The 6-PHMO prepared in Example 3 1 H NMR spectrum; Figure 2 6-PAHO prepared in Example 8 1 H NMR spectrum; Figure 3 6-PHMDA prepared in Example 13 1 H NMR spectrum; Figure 4 GPC plots for 2NO-FW40, 12NO-FW40, and SiPUU; Figure 5 Stress-strain diagrams for various mechanical properties of 2NO-FW40; Figure 6 Stress-strain diagrams for various mechanical properties of 12NO-FW40; Figure 7 Stress-strain diagrams for various mechanical properties of SiPUU; Figure 8 Schematic diagram of attenuation test after material is drilled Figure 9 The attenuation stress-strain diagram after drilling a single hole in 2NO-FW40; Figure 10 The attenuation stress-strain diagram after drilling a single hole in 12NO-FW40; Figure 11 The diagram shows the attenuation stress-strain pattern after drilling a single hole in a SiPUU. Figure 12 The attenuation stress-strain diagram after drilling two holes in 2NO-FW40; Figure 13 The attenuation stress-strain diagram after drilling two holes in 12NO-FW40; Figure 14 The attenuation stress-strain diagram after drilling two holes in SiPUU; Figure 15 Fluorescence images of cell adhesion experiments for 2NO-FW40, 12NO-FW40, and SiPUU materials.

[0068] Example

[0069] raw materials Some of the chemicals mentioned in the specification (including the examples below) can be obtained from the suppliers indicated in Table 1. It should be noted that chemicals not specifically mentioned in this invention can be purchased from suppliers.

[0070] Table 1. Suppliers of the selected compounds disclosed in the examples

[0071] process To better understand the synthesis steps of an adjustable chain length thermoplastic polyurethane-polyurethane urea elastomer material disclosed in this specification, the synthesis flow of some embodiments is shown below: It should be understood that the monomers in the following process can be arbitrarily replaced to synthesize the target compound. The carbon chain length of the monomers includes, but is not limited to, the lengths mentioned in the process and in this specification, so as to achieve the purpose of controllable chain length.

[0072] Process 1: Polydiol macromolecules after chain length adjustment (taking Example 3 as an example)

[0073] Process 2: Polyalkyl alcoholamine macromolecules after chain length adjustment (taking Example 8 as an example)

[0074] Step 3: Polyalkylene diamine macromolecules after chain length adjustment (taking Example 13 as an example)

[0075] Process 4: One-pot synthesis of polyurethane urea thermoplastic elastomer composite material (taking 2NO-FW40 in Example 18 as an example)

[0076] Example 1

[0077] Synthesis of 2-PHMO with chain length adjusted: Before the reaction begins, place the 500mL Shrek flasks and magnetic flasks required for the synthesis in a vacuum oven at 105°C. o After drying at C for ten minutes, remove the bottle and add 1,2-ethylene glycol (0.621 g, 10 mmol), 1,2-dibromoethane (1.785 g, 9.5 mmol), and sodium tert-butoxide (1.922 g, 20 mmol) dissolved in 100 mL of anhydrous tetrahydrofuran. Heat at 80 °C under a nitrogen atmosphere. oThe reaction was carried out at C for 24 hours. After the reaction was completed, the precipitate was poured into methanol while still hot, filtered and dried to obtain pure 2-PHMO.

[0078] Example 2 Synthesis of 4-PHMO with chain length adjusted: Before the reaction began, the 500 mL Shrek flasks required for the synthesis were dried in a vacuum oven at 105 °C for ten minutes. Then, 1,4-butanediol (0.912 g, 10 mmol), 1,4-dibromobutane (2.051 g, 9.5 mmol), and sodium tert-butoxide (2.764 g, 20 mmol) were added to the flasks and dissolved in 100 mL of anhydrous tetrahydrofuran. The reaction was carried out at 80 °C for 24 hours under a nitrogen atmosphere. After the reaction was completed, the precipitate was poured into methanol while hot, filtered, and dried to obtain pure 4-PHMO.

[0079] Example 3 Synthesis of 6-PHMO with chain length adjusted: Before the reaction begins, place the 500mL Shrek flasks and magnetic flasks required for the synthesis in a vacuum oven at 105°C. o After drying at C for ten minutes, remove the product and add 1,6-hexanediol (1.182 g, 10 mmol), 1,6-dibromohexane (2.318 g, 9.5 mmol), and sodium tert-butoxide (1.922 g, 20 mmol) to the flask. Dissolve the 1,6-hexanediol in 100 mL of anhydrous tetrahydrofuran and react at 80 °C for 24 hours under a nitrogen atmosphere. After the reaction is complete, pour the precipitate into methanol while hot, filter and dry to obtain pure 6-PHMO.

[0080] Example 4 Synthesis of 8-PHMO with chain length adjusted: Before the reaction began, the 500 mL Shrek flasks used in the synthesis were dried in a vacuum oven at 105 °C for ten minutes. Then, 1,8-octanediol (1.462 g, 10 mmol), 1,8-dibromooctane (2.720 g, 9.5 mmol), and sodium tert-butoxide (1.922 g, 20 mmol) were dissolved in 100 mL of anhydrous tetrahydrofuran. The reaction was carried out at 80 °C for 24 hours under a nitrogen atmosphere. After the reaction was completed, the precipitate was poured into methanol while hot. After filtration and drying, pure 8-PHMO was obtained.

[0081] Example 5

[0082] Synthesis of 12-PHMO with chain length adjusted: Before the reaction began, the 500 mL Shrek flasks required for the synthesis were dried in a vacuum oven at 105 °C for ten minutes. Then, 1,12-dodecanediol (2.023 g, 10 mmol), 1,12-dibromododecane (3.117 g, 9.5 mmol), and sodium tert-butoxide (1.922 g, 20 mmol) were dissolved in 100 mL of anhydrous tetrahydrofuran. The reaction was carried out at 80 °C for 24 hours under a nitrogen atmosphere. After the reaction was completed, the precipitate was poured into methanol while hot. After filtration and drying, pure 12-PHMO was obtained.

[0083] Example 6 Synthesis of 2-PAHO with chain length adjusted: Before the reaction began, the 500 mL Shrek flasks required for the synthesis were dried in a vacuum oven at 105 °C for ten minutes. Then, ethanolamine (0.611 g, 10 mmol), 1,2-dibromoethane (1.785 g, 9.5 mmol), and potassium carbonate (1.922 g, 20 mmol) were added to the flasks and dissolved in 100 mL of anhydrous tetrahydrofuran. The reaction was carried out at 80 °C for 24 hours under a nitrogen atmosphere. After the reaction was completed, the precipitate was poured into methanol while hot. After filtration and drying, pure 2-PAHO was obtained.

[0084] Example 7 Synthesis of 4-PAHO with chain length adjusted Before the reaction began, the 500 mL Shrek flasks required for the synthesis were dried in a vacuum oven at 105 °C for ten minutes. Then, 4-amino-1-butanol (0.891 g, 10 mmol), 1,4-dibromobutane (2.051 g, 9.5 mmol), and potassium carbonate (1.922 g, 20 mmol) were added to the flasks and dissolved in 100 mL of anhydrous tetrahydrofuran. The reaction was carried out at 80 °C for 24 hours under a nitrogen atmosphere. After the reaction was completed, the precipitate was poured into methanol while hot. After filtration and drying, pure 4-PAHO was obtained.

[0085] Example 8 Synthesis of 6-PAHO with chain length adjusted: Before the reaction began, the 500 mL Shrek flasks required for the synthesis were dried in a vacuum oven at 105 °C for ten minutes. Then, 6-amino-1-hexanol (1.172 g, 10 mmol), 1,6-dibromohexane (2.318 g, 9.5 mmol), and potassium carbonate (1.922 g, 20 mmol) were added to the flasks and dissolved in 100 mL of anhydrous tetrahydrofuran. The reaction was carried out at 80 °C for 24 hours under a nitrogen atmosphere. After the reaction was completed, the precipitate was poured into methanol while hot. After filtration and drying, pure 6-PAHO was obtained.

[0086] Example 9 Synthesis of 8-PAHO with chain length adjusted Before the reaction began, the 500 mL Shrek flasks required for the synthesis were dried in a vacuum oven at 105 °C for ten minutes. Then, 8-amino-1-octanol (1.4524 g, 10 mmol), 1,8-dibromooctane (2.720 g, 9.5 mmol), and potassium carbonate (1.922 g, 20 mmol) were added to the flasks and dissolved in 100 mL of anhydrous tetrahydrofuran. The reaction was carried out at 80 °C for 24 hours under a nitrogen atmosphere. After the reaction was completed, the precipitate was poured into methanol while hot. After filtration and drying, pure 8-PAHO was obtained.

[0087] Example 10 Synthesis of 12-PAHO with chain length adjusted Before the reaction began, the 500 mL Shrek flasks used in the synthesis were dried in a vacuum oven at 105 °C for ten minutes. Then, 12-amino-1-n-dodecanool (2.014 g, 10 mmol), 1,12-dibromododecane (3.281 g, 9.5 mmol), and potassium carbonate (1.922 g, 20 mmol) were added to the flasks and dissolved in 100 mL of anhydrous tetrahydrofuran. The reaction was carried out at 80 °C for 24 hours under a nitrogen atmosphere. After the reaction was completed, the precipitate was poured into methanol while hot. After filtration and drying, pure 12-PAHO was obtained.

[0088] Example 11 Synthesis of 2-PHMDA with chain length adjusted Before the reaction began, the 500 mL Shrek flasks required for the synthesis were dried in a vacuum oven at 105 °C for ten minutes. Then, under ice-water bath conditions, ethylenediamine (0.601 g, 10 mmol), 1,2-dibromoethane (1.785 g, 9.5 mmol), and potassium carbonate (1.922 g, 20 mmol) were added to the flasks and dissolved in 100 mL of anhydrous tetrahydrofuran. After the reaction stabilized, the mixture was reacted at 80 °C for 24 hours under a nitrogen atmosphere. After the reaction was completed, the mixture was poured into methanol while hot to precipitate the product. After filtration and drying, pure 2-PHMDA was obtained.

[0089] Example 12 Synthesis of 4-PHMDA with chain length adjusted Before the reaction began, the 500 mL Shrek flasks required for the synthesis were dried in a vacuum oven at 105 °C for ten minutes. Then, under ice-water bath conditions, 1,4-butanediamine (0.882 g, 10 mmol), 1,4-dibromobutane (2.051 g, 9.5 mmol), and potassium carbonate (1.922 g, 20 mmol) were added to the flasks and dissolved in 100 mL of anhydrous tetrahydrofuran. After the reaction stabilized, the reaction was carried out at 80 °C for 24 hours under a nitrogen atmosphere. After the reaction was completed, the precipitate was poured into methanol while hot, filtered, and dried to obtain pure 4-PHMDA.

[0090] Example 13 Synthesis of 6-PHMDA with chain length adjusted Before the reaction began, the 500 mL Shrek flasks required for the synthesis were dried in a vacuum oven at 105 °C for ten minutes. Then, under ice-water bath conditions, 1,6-hexanediamine (1.162 g, 10 mmol), 1,6-dibromohexane (2.318 g, 9.5 mmol), and potassium carbonate (1.922 g, 20 mmol) were added to the flasks and dissolved in 100 mL of anhydrous tetrahydrofuran. After the reaction stabilized, the reaction was carried out at 80 °C for 24 hours under a nitrogen atmosphere. After the reaction was completed, the precipitate was poured into methanol while hot, filtered, and dried to obtain pure 6-PHMDA.

[0091] Example 14 Synthesis of 8-PHMDA with chain length adjusted Before the reaction began, the 500 mL Shrek flasks used for the synthesis were dried in a vacuum oven at 105 °C for ten minutes. Then, under ice-water bath conditions, 1,8-octanediamine (1.4426 g, 10 mmol), 1,8-dibromooctane (2.720 g, 9.5 mmol), and potassium carbonate (1.922 g, 20 mmol) were added to the flasks and dissolved in 100 mL of anhydrous tetrahydrofuran. After the reaction stabilized, the mixture was reacted at 80 °C for 24 hours under a nitrogen atmosphere. After the reaction was completed, the mixture was poured into methanol while hot to precipitate the product. After filtration and drying, pure 8-PHMDA was obtained.

[0092] Example 15 Synthesis of 12-PHMDA with chain length adjusted Before the reaction began, the 500 mL Shrek flasks and magnetic flasks required for the synthesis were dried in a vacuum oven at 105 °C for ten minutes. Then, under ice-water bath conditions, 1,12-dodecanediamine (2.004 g, 10 mmol), 1,12-dibromododecane (3.281 g, 9.5 mmol), and potassium carbonate (1.922 g, 20 mmol) were added to the flasks and dissolved in 100 mL of anhydrous tetrahydrofuran. After the reaction stabilized, the reaction was carried out at 80 °C for 24 hours under a nitrogen atmosphere. After the reaction was completed, the precipitate was poured into methanol while hot, filtered, and dried to obtain pure 12-PHMDA.

[0093] Table 2 presents the monomer characteristics after chain length adjustment. Table 2. Monomer molecular weight information after chain length adjustment

[0094] Example 16 One-pot preparation of polyurethane-urea thermoplastic elastomer composite material 2O-FW40 with chain segment length adjustment Place 100.0 g of pre-dried 2-PHMO into a three-necked round-bottom flask equipped with a magnetic stirrer. Place the flask in an oil bath at 80°C. Add 17.53 g of molten MDI into an adding funnel and stir over 1 minute to add 2-PHMO. Allow the reaction mixture to react further under a nitrogen atmosphere for two hours before use.

[0095] Subsequently, 8.5 g of the above prepolymer, 7.29 g of MDI, and 10.0 g of α,ω-bis-(6-hydroxyethoxypropyl)polydimethylsiloxane were weighed and rapidly added to a three-necked round-bottom flask equipped with a mechanical stirrer using a feeding funnel, and stirred thoroughly to combine. After complete addition, the reaction mixture was heated to 80°C under nitrogen protection and stirred continuously for 2 hours. Then, 2.41 g of 1,3-bis(4-hydroxybutyl)tetramethyldisiloxane was used to extend the chain of the prepolymer, and the reaction was continued to be stirred under nitrogen atmosphere for 2 hours. The reaction mixture was then cooled to 0°C, and 178 mL of anhydrous DMAc was added and stirred thoroughly to dissolve, yielding a transparent prepolymer solution. 0.521 g of EDA was dissolved in 3 mL of DMAc and added dropwise to the reaction mixture using a dropping funnel, stirring slowly until all EDA was added. Stirring continued for 30 minutes until the chain extender had reacted completely and the solution viscosity increased. The reaction mixture was then heated to 80 °C and stirred until the reaction was complete and a clear solution was obtained. The reaction progress was monitored by FTIR, and the reaction was found to have a viscosity of 2270 cm⁻¹. -1 The disappearance of the absorption peak indicates that the reaction is complete. The 2O-FW40 solution was transferred to a screw-cap glass bottle under a nitrogen atmosphere and stored at room temperature.

[0096] Based on the above reaction conditions, by simply replacing the soft block 2-PHMO with 4-PHMO, 6-PHMO, 8-PHMO and 12-PHMO, polyurethane urea thermoplastic elastomer composites 4O-FW40, 6O-FW40, 8O-FW40 and 12O-FW40 with chain length adjustment were obtained.

[0097] Example 17 One-pot preparation of polyurethane-urea thermoplastic elastomer composite material 2NO-FW40 with chain segment length adjustment Place 100g of pre-dried 2-PAHO into a three-necked round-bottom flask equipped with a magnetic stirrer. Place the flask in an oil bath at 80°C. Add 17.53g of molten MDI into an adding funnel and stir over 1 minute to add 2-PAHO. Allow the reaction mixture to react further under a nitrogen atmosphere for two hours before use.

[0098] Subsequently, 8.5 g of the above prepolymer, 7.29 g of MDI, and 10.0 g of α,ω-bis-(6-hydroxyethoxypropyl)polydimethylsiloxane were weighed and rapidly added to a three-necked round-bottom flask equipped with a mechanical stirrer using a feeding funnel, and stirred thoroughly to combine. After complete addition, the reaction mixture was heated to 80°C under nitrogen protection and stirred continuously for 2 hours. Then, 2.41 g of 1,3-bis(4-hydroxybutyl)tetramethyldisiloxane was used to extend the chain of the prepolymer, and the reaction was continued to be stirred under nitrogen atmosphere for 2 hours. The reaction mixture was then cooled to 0°C, and 178 mL of anhydrous DMAc was added and stirred thoroughly to dissolve, yielding a transparent prepolymer solution. 0.521 g of EDA was dissolved in 3 mL of DMAc and added dropwise to the reaction mixture using a dropping funnel, stirring slowly until all EDA was added. Stirring continued for 30 minutes until the chain extender had reacted completely and the solution viscosity increased. The reaction mixture was then heated to 80°C and stirred until the reaction was complete, yielding a clear solution. The reaction progress was monitored by FTIR, and a value of 2270 cm⁻¹ was observed. -1 The disappearance of the absorption peak indicates that the reaction is complete. The 2NO-FW40 solution was transferred to a screw-cap glass bottle under a nitrogen atmosphere and stored at room temperature.

[0099] Based on the above reaction conditions, by simply replacing the soft block 2-PAHO with 4-PAHO, 6-PAHO, 8-PAHO and 12-PAHO, polyurethane urea thermoplastic elastomer composites 4NO-FW40, 6NO-FW40, 8NO-FW40 and 12NO-FW40 with adjusted chain lengths were obtained.

[0100] Example 18 One-pot preparation of polyurethane-urea thermoplastic elastomer composite material 2N-FW40 with chain segment length adjustment Place 100g of pre-dried 2-PHMDA into a three-necked round-bottom flask equipped with a magnetic stirrer. Place the flask in an oil bath at 80°C. Add 17.53g of molten MDI into an adding funnel and stir over 1 minute to add 2-PHMDA. Allow the reaction mixture to react further under a nitrogen atmosphere for two hours before use.

[0101] Subsequently, 8.5 g of the above prepolymer, 7.29 g of MDI, and 10.0 g of α,ω-bis-(6-hydroxyethoxypropyl)polydimethylsiloxane were weighed and rapidly added to a three-necked round-bottom flask equipped with a mechanical stirrer using a feeding funnel, and stirred thoroughly to combine. After complete addition, the reaction mixture was heated to 80°C under nitrogen protection and stirred continuously for 2 hours. Then, 2.41 g of 1,3-bis(4-hydroxybutyl)tetramethyldisiloxane was used to extend the chain of the prepolymer, and the reaction was continued to be stirred under nitrogen atmosphere for 2 hours. The reaction mixture was then cooled to 0°C, and 178 mL of anhydrous DMAc was added and stirred thoroughly to dissolve, yielding a transparent prepolymer solution. 0.521 g of EDA was dissolved in 3 mL of DMAc and added dropwise to the reaction mixture using a dropping funnel, stirring slowly until all EDA was added. Stirring continued for 30 minutes until the chain extender had reacted completely and the solution viscosity increased. The reaction mixture was then heated to 80 °C and stirred until the reaction was complete and a clear solution was obtained. The reaction progress was monitored by FTIR, and the reaction was found to have a viscosity of 2270 cm⁻¹. -1 The disappearance of the absorption peak indicates that the reaction is complete. The 2N-FW40 solution was transferred to a screw-cap glass bottle under a nitrogen atmosphere and stored at room temperature.

[0102] Based on the above reaction conditions, by simply replacing the soft block 2-PHMDA with 4-PHMDA, 6-PHMDA, 8-PHMDA and 12-PHMDA, polyurethane urea thermoplastic elastomer composites 4N-FW40, 6N-FW40, 8N-FW40 and 12N-FW40 with chain length adjustment were obtained.

[0103] Comparative Example 1: SiPUU Addition Synthesis Method SiPUU was synthesized with reference to CN108290992A.

[0104] Synthetic urethane-linked poly(epoxyhexane) (PHMO-u-PHMO) PHMO was dried and degassed by heating at 105 °C under vacuum (0.1 torr) for approximately 15 hours until the moisture content was below 200 ppm, as determined by Karl Fisher titration. All glassware used in the experiment was dried overnight at 105 °C before use. Accurately weighed molten 4,4'-methylene diphenyl diisocyanate (MDI) (7.18 g) was placed in a round-bottom flask equipped with a mechanical stirrer, dropping funnel, and nitrogen inlet. The flask was then placed in an oil bath at 80 °C. Pre-dried PHMO (40.00 g) was weighed and added to the MDI over 20-minute intervals with stirring. The reaction mixture was allowed to react further for approximately 2 hours until all isocyanate was consumed, as determined by the absence of 2275 cm⁻¹. -1 The IR absorption at that location provides proof.

[0105] In a flask, precisely weighed PHMO-u-PHMO (10.00 g) prepared according to the method of Example 1 and α,ω-bis(hydroxyethoxypropyl)polydimethylsiloxane (PDMS) (MW950, 40.00 g) were mixed and degassed under vacuum (0.1 torr) at 80 °C for 2 hours. MDI (22.94 g) was precisely weighed into a round-bottom flask equipped with a mechanical stirrer, a dropping funnel, and a nitrogen inlet. The flask was then placed in an oil bath at 80 °C. Over a period of 30 minutes, the mixture of PHMO-u-PHMO and PDMS was slowly added to the MDI in the flask with stirring using a dropping funnel. After the addition was complete, the reaction mixture was heated at 80 °C with stirring under nitrogen for 2 hours. Then, using a syringe, anhydrous N'N-dimethylacetamide (DMAc, 500 mL) was added to the reaction mixture, and the mixture was stirred for 5 minutes until a clear solution was obtained. The solution was cooled to 0°C in an ice bath, and 1,3-bis-(3-aminopropyl)tetramethyldisiloxane (BAPD, 10.40 g), dissolved in anhydrous DMAc (25 mL), was added dropwise to the prepolymer solution in the flask with stirring. After the addition was complete, the polymer solution was heated to 90°C over a period of 3 hours and then transferred to a Schott flask.

[0106] Example 19 Mechanical property tests of various nitrogen-oxygen-carbon block-siloxane composite-bonded polyurethane-urea thermoplastic elastomers under different film-forming methods: To investigate the effects of different film-forming methods on the mechanical properties of materials, we used three different film-forming methods to test their mechanical properties, and finally determined a relatively superior film-forming method through comparison.

[0107] Film formation method 1: The obtained polymer solution was added into a tetrafluoroethylene dish mold, placed in a nitrogen circulating oven, and the solvent was slowly evaporated at 60°C until it was completely evaporated. Then it was placed in a 60°C vacuum oven and left overnight at a vacuum of 0.1 torr to remove residual solvent, resulting in a polymer film with an area of ​​80mm × 150mm and a thickness of 0.5mm. After equilibration at room temperature, the next step of the experiment was carried out.

[0108] Film formation method two: The obtained polymer solution was added into a tetrafluoroethylene dish mold, placed in a 60°C vacuum oven, and the solvent was removed under a vacuum of 0.1 torr to obtain a polymer film with an area of ​​80 mm × 150 mm and a thickness of 0.5 mm. After being placed at room temperature for equilibration, the next step of the experiment was carried out.

[0109] Film formation method three: In a cleanroom, a spin coater was prepared in advance. A clean silicon wafer was placed on the spin coater and vacuum adsorption was activated. Then, a pipette was used to pick up the degassed polymer solution and perform a spin coating operation at 500 rpm for 8 seconds, a spin coating operation at 3000 rpm for 40 seconds, and a drying operation at 6000 rpm for 20 seconds. The above operations were then repeated until a polymer film with an area of ​​80 mm × 150 mm and a thickness of 0.5 mm was obtained. After equilibration at room temperature, the next step of the experiment was carried out.

[0110] The polymer film was placed on a stamping machine and cut into dumbbell-shaped stretch standard strips using a standard die. The strips were 75 mm long, 13 mm wide at both ends, 4 mm wide at the narrower center, 25 mm long, and 0.5 mm thick.

[0111] We selected two materials, 2NO-FW40 and 12NO-FW40, with N:C ratios of 1:4 and 1:24, respectively, to test their mechanical properties in order to explore a more suitable film formation method. As a comparison, we selected SiPUU, the material in Patent Comparative Example 1, and first tested the molecular weight of the three materials respectively.

[0112] Table 3. Molecular weights of 2NO-FW40, 12NO-FW40, and SiPUU

[0113] Next, mechanical property tests were conducted. At room temperature, dumbbell-shaped tensile standard specimens were fixed to the upper and lower clamps of a universal tensile testing machine. The clamp gap was the narrowest part of the specimen's center. The initial gauge length was 10 mm, and the tensile speed was 50 mm / min until the specimen broke, at which point the tensile test ended. Tensile standard specimens for 2NO-FW40, 12NO-FW40, and SiPUU were obtained using three different film-forming methods, and the test data (maximum force, tensile strength, elongation at break, elastic modulus, and maximum deformation) are shown in Tables 4-6.

[0114] Table 4. Mechanical Properties Tests of 2NO-FW40

[0115] Table 5. Mechanical Properties Tests of 12NO-FW40

[0116] Table 6. Mechanical Properties Tests of SiPUU

[0117] Experimental comparisons show that among the three film-laying methods, the spline obtained by method three has the best performance. Appropriately increasing the proportion of nitrogen atoms in the material's molecular chain can significantly improve the material's various mechanical properties.

[0118] Example 20 Post-drilling degradation test of various nitrogen-oxygen-carbon ratio block-siloxane composite-bonded polyurethane-urea thermoplastic elastomer composites under different film formation methods: The dumbbell-shaped standard tensile specimens of 2NO-FW40, 12NO-FW40 and SiPUU materials were laser-pierced at the center of the original gauge length using an LPKF laser cutter with a laser power of 1.5W and 50 cuts until a 0.3mm diameter hole was cut. The attenuation test was then performed on the specimen material after single-hole drilling, i.e., the various mechanical properties of the material were tested on a universal tensile testing machine.

[0119] Table 7. Attenuation test of 2NO-FW40 after single-hole drilling

[0120] Note: The attenuation rate after drilling is calculated based on the result of Method 3, which yields the best mechanical properties before and after drilling.

[0121] Attenuation rate = (Parameter before drilling - Parameter after drilling) / Parameter before drilling × 100%.

[0122] Table 8. Attenuation test of 12NO-FW40 after single-hole drilling

[0123] Note: The attenuation rate after drilling is calculated based on the result of Method 3, which yields the best mechanical properties before and after drilling.

[0124] Attenuation rate = (Parameter before drilling - Parameter after drilling) / Parameter before drilling × 100%.

[0125] Table 9. SiPUU Single-Hole Drilling Attenuation Test

[0126] Note: The attenuation rate after drilling is calculated based on the result of Method 3, which yields the best mechanical properties before and after drilling.

[0127] Attenuation rate = (Parameter before drilling - Parameter after drilling) / Parameter before drilling × 100%.

[0128] Next, to further highlight the actual strength of the material as a sewn valve, two 0.3 mm diameter holes were uniformly cut at the center of the original gauge length of the dumbbell-shaped standard tensile specimens of 2NO-FW40, 12NO-FW40 and SiPUU materials, with a hole spacing of 1.2 mm. The attenuation test after double-hole drilling of the specimen material was carried out, that is, the various mechanical properties of the material were tested on a universal tensile testing machine.

[0129] Table 10. Attenuation test after dual-hole drilling of 2NO-FW40

[0130] Note: The attenuation rate after drilling is calculated based on the result of Method 3, which yields the best mechanical properties before and after drilling.

[0131] Attenuation rate = (Parameter before drilling - Parameter after drilling) / Parameter before drilling × 100%.

[0132] Table 11. Attenuation test after dual-hole drilling of 12NO-FW40

[0133] Note: The attenuation rate after drilling is calculated based on the result of Method 3, which yields the best mechanical properties before and after drilling.

[0134] Attenuation rate = (Parameter before drilling - Parameter after drilling) / Parameter before drilling × 100%.

[0135] Table 12. SiPUU Attenuation Test After Dual-Hole Drilling

[0136] Note: The attenuation rate after drilling is calculated based on the result of Method 3, which yields the best mechanical properties before and after drilling.

[0137] Attenuation rate = (Parameter before drilling - Parameter after drilling) / Parameter before drilling × 100%.

[0138] Experimental comparisons revealed that among the three film-laying methods, method three yielded the best spline performance. Appropriately increasing the nitrogen atom ratio in the material molecular chain can significantly improve the material's mechanical properties and post-drilling attenuation. 2NO-FW40 and 12NO-FW40 showed lower performance degradation in the post-drilling attenuation test, while SiPUU showed a larger performance degradation. Furthermore, 2NO-FW40 and 12NO-FW40 outperformed SiPUU in all aspects of mechanical properties, mechanical properties, and post-drilling attenuation.

[0139] Example 21 Mechanical property tests of various nitrogen-oxygen-carbon ratio block-siloxane composite-bonded polyurethane-urea thermoplastic elastomer composites: The experimental data from Examples 16-18 demonstrate that the samples obtained using film formation method three have relatively good performance. Therefore, we then used standard samples prepared using film formation method three to conduct mechanical property tests on 2O-FW40, 4O-FW40, 6O-FW40, 8O-FW40, 12O-FW40, 4NO-FW40, 6NO-FW40, 8NO-FW40, 2N-FW40, 4N-FW40, 6N-FW40, 8N-FW40, and 12N-FW40 as follows: Table 13. Characteristic information of polyurethane urea thermoplastic elastomer composites after chain length adjustment.

[0140] Example 22 Cell adhesion assays of 2NO-FW40, 12NO-FW40, and SiPUU: 2NO-FW40, 12NO-FW40, and SiPUU were cut into 5 mm diameter, 0.5 mm thick circular standard samples. The discs were soaked in alcohol for 15 min, washed five times with ultrapure water, and then soaked in D-PBS. After preparing the cells, the discs were placed at the bottom of a 96-well plate. Human endothelial cells (HUVEC-T1, Cell Resource Center, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences) were cultured and passaged at least twice, and cells in the logarithmic growth phase were harvested at 1 × 10⁻⁶ cells / well. 4 Cells were seeded at a density per well. Separate groups were set up for the material cell group and a negative control (culture medium) group. After 48 hours of culture, fluorescent dye was added according to the instructions of the Calein / PI cell viability and cytotoxicity assay kit. After cell incubation, the cells were observed and photographed using a dual-disc fluorescence confocal microscope to observe cell death results. Dead cells were labeled with red fluorescence (PI), and live cells were labeled with green fluorescence (Calcein).

[0141] The cell adhesion data of 2NO-FW40, 12NO-FW40, and SiPUU were obtained after fluorescence quantification, as shown in Table 14. It was found that the cell viability of the 2NO-FW40 and 12NO-FW40 groups was high, both above 95%, with endothelial cells adhering easily and evenly, indicating good cell condition. In contrast, the cell viability of the SiPUU group was low, at only 58.70%, with endothelial cells adhering but unevenly distributed, and significant apoptosis. Therefore, 2NO-FW40 and 12NO-FW40 exhibit superior anti-cell adhesion and cell activity compared to SiPUU.

[0142] Table 14. Fluorescence Quantification Table for Cell Adhesion Assay

[0143] Obviously, the above embodiments are merely illustrative examples for clear explanation and are not intended to limit the implementation. Those skilled in the art will recognize that other variations or modifications can be made based on the above description. It is neither necessary nor possible to exhaustively list all possible implementations here. However, obvious variations or modifications derived therefrom are still within the scope of protection of this invention.

Claims

1. A copolymer segment having the structure shown in Formula I: ； in, A1 and A2 are independently selected as hydrogen, hydroxyl, or amino; The monomer of B1 is selected from diols, diamines, or alkanolamines; The monomer of B2 is selected from alcohol amines; The diol is selected from siloxane diols, alkane diols, carbonate diols, or ester diols; The diamine is selected from siloxane diamines, alkane diamines, carbonate diamines, or ester diamines; The alkanolamine is selected from siloxane alkanolamines, alkane alkanolamines, carbonate alkanolamines, or ester alkanolamines; The monomers of C1 and C2 are independently selected from alkane dihalogenated compounds, ether dihalogenated compounds, aromatic dihalogenated compounds, ester dihalogenated compounds, or siloxane dihalogenated compounds. Substituent D 1 D 2 It is a divalent linker containing the following groups: urea linker group -NH-CO-NH- and / or carbamate group -NH-COO-, D 1 D 2 The monomer is a diisocyanate; m is selected from integers from 1 to 10; n is an integer selected from 0 to 10; E is a part of formula A or formula B; ； R2, R3, R5 and R6 are each independently selected from hydrogen or optionally substituted straight-chain, branched or cyclic, saturated and unsaturated C1-C6 hydrocarbon groups. R1 and R4 are respectively independent of each other straight-chain, branched or cyclic, saturated and unsaturated alkylene groups, which are optionally separated by one or more heteroatoms independently selected from O, N and S. x is an integer from 1 to 50; ； R7 and R8 are independently selected from straight-chain, branched or cyclic, saturated or unsaturated alkylene groups, monocyclic, polycyclic or fused-ring, carbocyclic and heterocyclic, substituted or unsubstituted aromatic groups. y is an integer from 1 to 60; z is an integer from 1 to 60.

2. The copolymer segment according to claim 1, wherein the siloxane diol is dimethylsiloxane diol, the siloxane diamine is dimethylsiloxane diamine, and the siloxane diolamine is dimethylsiloxane diolamine; The alkane diols, alkane diamines, and alkane diolamines are independently selected from C2-C20 straight-chain, branched, or cyclic, saturated, and unsaturated hydrocarbon diols, diamines, or diolamines. The carbonate diols, carbonate diamines, and carbonate diolamines are independently selected from straight-chain, branched, or cyclic, saturated and unsaturated C2-C20 carbonate diols, diamines, or diolamines. The ester diols, ester diamines, and ester diolamines are independently selected from straight-chain, branched, or cyclic, saturated and unsaturated C2-C20 ester diols, diamines, or diolamines.

3. A polyurethane urea composite material comprising the following monomers: At least one copolymer segment of Formula I according to any one of claims 1-2, a diisocyanate, a polysiloxane diol, and one or more chain extenders.

4. The composite material according to claim 3, wherein the diisocyanate is selected from 1,4-diisocyanate butane, 1,12-diisocyanate dodecane, 1,6-diisocyanate hexane, 1,8-diisocyanate octane, 4,4′-methylene diphenyl diisocyanate, 4,4′-methylene bis(cyclohexyl) diisocyanate, p-phenylene diisocyanate, m-phenylene diisocyanate, trans-cyclohexane-1,4-diisocyanate or a mixture of cis and trans isomers, 1,6-hexene diisocyanate, 2,4-toluene diisocyanate, 2,6-toluene diisocyanate, p-tetramethylxylene diisocyanate, isophorone diisocyanate and m-tetramethylxylene diisocyanate, 1,6-diisocyanate hexane, 1,3-bis(1-isocyanate-1-methylethyl)benzene and 1,5-diisocyanate naphthalene.

5. The composite material according to claim 3, wherein the at least one chain extender is selected from C1-12 alkyldiol, C1-12 alkyldiamine and C1-12 alkyldiolamine.

6. The composite material according to claim 3, wherein the at least one chain extender is selected from 1,4-butanediol, 1,6-hexanediol, 1,8-octanediol, 1,9-nonanediol, 1,10-decanediol, 1,4-cyclohexanediol, p-xylene glycol, 1,4-bis(2-hydroxyethoxy)benzene, 1,12-dodecanediol, 1,3-bis-(4-hydroxybutyl)1,1,3,3-tetramethyldisiloxane, 1,2-ethylenediamine, ethanolamine, 1,4-butanediamine, 1,3-propanediamine, 1,3-bis-(3-aminopropyl)tetramethyldisiloxane, and 1,3-bis-(3-aminobutyl)tetramethyldisiloxane.

7. A medical device comprising, wholly or partially, the polyurethane or polyurethane urea elastomer material of any one of claims 3-6.

8. The medical device according to claim 7, wherein the medical device is selected from cardiac pacemakers, defibrillators, catheters, heart valves, cardiac assist devices, artificial blood vessels, implantable prostheses, cannulas, external devices, artificial organs, pacemaker leads, defibrillator leads, blood pumps, balloon pumps, arteriovenous shunts, biosensors, cell encapsulation membranes, drug delivery devices, wound dressings, artificial joints, orthopedic implants, and soft tissue substitutes.

9. The medical device according to claim 7, wherein the medical device is a heart valve.

10. A method for preparing the medical device according to claim 9, characterized in that, Using the composite material according to any one of claims 3-6, a spin coater is used to perform a homogenization operation, a film spinning operation, and a drying operation; the above operations are then repeated continuously until a polymer film is obtained, and the film is formed into the shape and size of a heart valve.

11. A method for preparing the composite material according to any one of claims 3-6, characterized in that, Using the I-segment of claim 1 or 2, diisocyanate is added, and after the polysiloxane diol reaction, a chain extender is added to extend the chain.

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