Degradable medical itaconic acid polyurethane material, preparation method and application thereof

Abstract

The application discloses a degradable medical itaconic acid polyurethane material and a preparation method and application thereof. The degradable medical itaconic acid polyurethane material has the structure shown in the following formula: R1 is a residue of a hydroxyl-terminated itaconic acid diol oligomer, R2 is a residue of a polyester diol, D is a residue of a diisocyanate, B is a residue of a linear diol, and n is a positive integer of 5-12. The preparation method comprises the following steps: performing esterification reaction and polycondensation reaction on itaconic acid, a short-chain diol, a polymerization inhibitor and a first catalyst to prepare a hydroxyl-terminated itaconic acid diol oligomer; then performing microwave prepolymerization reaction on the hydroxyl-terminated itaconic acid diol oligomer, a polyester diol, a diisocyanate, a solvent and a second catalyst, and continuously performing chain extension reaction on the hydroxyl-terminated itaconic acid diol oligomer by adding a linear diol to prepare the degradable medical itaconic acid polyurethane material. The itaconic acid polyurethane material prepared by the application has the properties of degradability, excellent mechanical property, stable thermodynamics and good biocompatibility.

Description

Technical Field

[0001] This invention belongs to the field of bio-based polymer materials technology, specifically relating to a biodegradable medical itaconic acid polyurethane material, its preparation method, and its application. Background Technology

[0002] Polyurethane, also known as polyurethane (PU), is an important polymer compound. It is produced by the addition polymerization reaction of diisocyanates containing at least two active groups with polyols. Polyurethane possesses a structure containing both soft and hard segments, with covalent bonds between them, resulting in a microphase-separated structure. This characteristic allows for structural adjustments to the polyurethane structure by modifying the soft and hard segment components or adding other fillers, thereby obtaining products with desired properties. In the 1830s, Dr. Bayer of Germany first invented polyurethane fiber (spandex fiber). After ninety years of development, numerous new soft and hard segment structures have emerged in polyurethane, giving it wider performance tunability and diversifying its product forms. Polyurethane foams, fibers, adhesives, and other products are widely used in interior decoration, road engineering, and drug delivery, demonstrating its widespread presence and product diversity.

[0003] By rationally designing the structure of polyurethane materials, biocompatible polyurethane materials can be obtained. Furthermore, subsequent modification methods can endow polyurethane with more functions. CN117599260A discloses the preparation and application of a medical polyurethane foam with anti-inflammatory function. First, polyurethane foam is prepared, and then particulate matter capable of decomposing reactive oxygen species is introduced into the foam body. Using an in-situ reduction reaction, reactive oxygen species are catalyzed to decompose into water and oxygen, thereby inhibiting the occurrence of inflammatory responses. It can be applied in medical fields such as sealing and filling, and hemostasis, but it does not possess certain biodegradability. CN118165190A discloses a method for surface functionalization modification of medical polyurethane materials. First, a diisocyanate-terminated polyurethane prepolymer is prepared, and then it is covalently grafted with dihydroxybenzophenone compounds under photoinitiation conditions to prepare a polyurethane material, thereby functionalizing the surface of the medical polyurethane material. However, its polyurethane matrix structure lacks innovation.

[0004] With the popularization of the concept of "green chemistry," the design approach of using petroleum-based raw materials to prepare polyurethane materials is no longer widely adopted. Furthermore, the extensive use of petroleum-based raw materials leads to serious environmental problems such as a shortage of environmentally friendly resources. Using bio-based resources to prepare polyurethane materials has become a new approach to achieve a greener and more environmentally friendly design and fabrication of polyurethane structures.

[0005] Therefore, how to prepare a new technology for polyurethane materials with degradable properties and good biocompatibility has been a long-term goal for researchers in the industry. Summary of the Invention

[0006] The main objective of this invention is to provide a biodegradable medical itaconic acid polyurethane material and its preparation method, so as to overcome the shortcomings of the prior art.

[0007] Another object of the present invention is to provide the application of the aforementioned biodegradable medical itaconic acid polyurethane material.

[0008] To achieve the aforementioned objectives, the technical solution adopted by this invention includes:

[0009] This invention provides a biodegradable medical itaconic acid polyurethane material having the structure shown in formula (I):

[0010]

[0011] Wherein, R1 is a residue of the hydroxyl-terminated itaconic acid diol oligomer, R2 is a residue of the polyester diol, D is a residue of the diisocyanate, B is a residue of the linear diol, and n is a positive integer from 5 to 12.

[0012] This invention also provides a method for preparing a biodegradable medical itaconic acid polyurethane material, comprising:

[0013] An esterification reaction and a polycondensation reaction are carried out on a first mixed reaction system containing itaconic acid, short-chain diol, polymerization inhibitor and first catalyst to obtain hydroxyl-terminated itaconic acid diol oligomer.

[0014] A second mixed reaction system containing itaconic acid diol oligomer, polyester diol, diisocyanate, solvent and a second catalyst is subjected to microwave prepolymerization reaction, and then a straight-chain diol is added to continue the chain extension reaction to obtain a biodegradable medical itaconic acid polyurethane material.

[0015] This invention also provides a biodegradable medical itaconic acid polyurethane material prepared by the aforementioned method.

[0016] This invention also provides the application of the aforementioned biodegradable medical itaconic acid polyurethane material in the preparation of medical implants.

[0017] Accordingly, this invention also provides a method for preparing a vascular transplant tubular material, which includes: preparing the vascular transplant tubular material by electrospinning the biodegradable medical itaconic acid polyurethane material.

[0018] Compared with the prior art, the beneficial effects of the present invention are at least as follows:

[0019] 1) This invention utilizes the active carboxyl structure of bio-based itaconic acid to synthesize hydroxyl-terminated itaconic acid diol oligomers, which, together with polyester diol, serve as the soft segment structure of polyurethane. The resulting itaconic acid polyurethane material exhibits degradability, excellent mechanical properties, stable thermodynamics, and good biocompatibility.

[0020] 2) The overall performance of the itaconic acid polyurethane material prepared by this invention is no less than that of pure commercial soft segment polyurethane material, and the material has an appropriate contact angle size to reduce adverse reactions such as bioadhesion. A new strategy for biodegradable medical implant polyurethane material is proposed. Attached Figure Description

[0021] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments recorded in the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0022] Figure 1 This is a schematic diagram of the synthesis process of the itaconic acid diol oligomer obtained in Example 1 of the present invention;

[0023] Figure 2 This is a schematic diagram of the synthesis process of the biodegradable medical itaconic acid polyurethane material prepared in Example 1 of the present invention;

[0024] Figure 3 This is a tensile property curve of the biodegradable medical itaconic acid polyurethane material prepared in Example 1 of the present invention;

[0025] Figure 4a and Figure 4b These are Masson and H&E staining images of tissues implanted in the body 30 days after the biodegradable medical itaconic acid polyurethane material in Example 1 of this invention.

[0026] Figure 5 This is the infrared spectrum of the biodegradable medical itaconic acid polyurethane material prepared in Example 1 of this invention;

[0027] Figure 6 This is a schematic diagram illustrating the biodegradability of the biodegradable medical itaconic acid polyurethane material prepared in Example 2 of the present invention. Detailed Implementation

[0028] In view of the problems existing in the prior art, after long-term research and a large number of experiments, the inventors of this case have proposed a biodegradable medical itaconic acid polyurethane material, which is prepared using itaconic acid raw materials from biomass. This itaconic acid polyurethane material has degradable properties, excellent mechanical properties, stable thermodynamics and good biocompatibility.

[0029] Itaconic acid (IA), one of the 12 highest value-added biomass chemicals listed by the U.S. Department of Energy, has one unsaturated double bond and two carboxyl groups in its structure. It is chemically active and can undergo various reactions such as addition, esterification, and polymerization. It also has anti-inflammatory, antibacterial, and antiviral effects, so it has great potential for use in the preparation of biomedical materials.

[0030] To facilitate understanding of the present invention, it will be described in more detail below. However, it should be understood that the present invention can be implemented in many different forms and is not limited to the embodiments or examples described herein. Rather, these embodiments or examples are provided to make the disclosure of the present invention more thorough and complete.

[0031] As one aspect of the technical solution of the present invention, a biodegradable medical itaconic acid polyurethane material has the structure shown in formula (I):

[0032]

[0033] In formula (I), R1 is a residue of the hydroxyl-terminated itaconic acid diol oligomer, R2 is a residue of the polyester diol, D is a residue of the diisocyanate, B is a residue of the linear diol chain extender, and n is a positive integer, ranging from 5 to 12.

[0034] In some embodiments, R1 is a residue of an itaconic acid diol oligomer prepared from itaconic acid and a short-chain diol.

[0035] Furthermore, the short-chain diol may include any one or more combinations of 1,2-ethylene glycol, 1,3-propanediol, 1,4-butanediol, 1,5-pentanediol, 1,6-hexanediol, etc., but is not limited thereto.

[0036] In structural formula (I), R1 is a hydroxyl-terminated itaconic acid diol oligomer residue, and R2 is a polyester diol residue. The polyester portion of this invention adopts a binary soft segment structure. The introduction of the itaconic acid oligomer diol portion creates a structure with side double bonds in the overall structure, which alters the thermodynamics and surface wettability of the material. For example, compared to polycaprolactone diol, the glass transition temperature of the material in this invention is higher, and the contact angle is larger.

[0037] Itaconic acid possesses one unsaturated double bond and two carboxyl groups, exhibiting highly reactive chemical properties and capable of undergoing various reactions such as addition, esterification, and polymerization. Utilizing the reactive carboxyl groups of itaconic acid to react with the hydroxyl groups of short-chain diols yields hydroxyl-terminated itaconic acid diol oligomers, providing a structural basis for the synthesis of itaconic acid polyurethanes. Furthermore, itaconic acid polyurethane materials prepared using itaconic acid diol oligomers possess a range of advantages, including being environmentally friendly and biodegradable.

[0038] In some implementations, R2 is derived from polyester glycol, which may include, but is not limited to, any one or a combination of two or more of polycaprolactone glycol, polyethylene glycol, and hexamethylene adipate.

[0039] Furthermore, the number-average molecular weight of the polyester diol is 500 to 2000.

[0040] In some implementations, B is derived from a straight-chain diol, which may include, but is not limited to, any one or a combination of two or more of 1,3-propanediol, 1,4-butanediol, 1,5-pentanediol, and 1,6-hexanediol. The use of a straight-chain diol in this invention enhances flexibility.

[0041] In some embodiments, D is derived from diisocyanates, which may include, but are not limited to, any one or more combinations of diphenylmethane diisocyanate, isophorone diisocyanate, terephthalic diisocyanate, 1,5-naphthalene diisocyanate, toluene diisocyanate and dicyclohexyl diisocyanate.

[0042] In some embodiments, the biodegradable medical itaconic acid polyurethane material includes soft segments containing residues of itaconic acid diol oligomers and polyester diols, and hard segments containing residues of diisocyanates and linear diols.

[0043] Furthermore, the soft segment content in the biodegradable medical itaconic acid polyurethane material is 50-70 wt%. When the soft segment content is high, the product has greater flexibility, and the binary aliphatic long-chain structure provides a certain degree of flexibility. When the ratio of itaconic acid diol oligomer to polyester diol in the soft segment increases, its overall flexibility will decrease due to the side double bonds in the itaconic acid diol oligomer.

[0044] Furthermore, the mass percentage of itaconic acid diol oligomer in the soft segment containing the residues of itaconic acid diol oligomer and the residues of polyester diol is 25% to 65%.

[0045] In some embodiments, the biodegradable medical itaconic acid polyurethane material of the present invention has a wide adjustable range, with a tensile modulus of 5 to 80 MPa, a tensile strength of 8.0 to 33.8 MPa, and an elongation at break of 170 to 500%.

[0046] As one aspect of the technical solution of this invention, a method for preparing a biodegradable medical itaconic acid polyurethane material includes:

[0047] An esterification reaction and a polycondensation reaction are carried out on a first mixed reaction system containing itaconic acid, short-chain diol, polymerization inhibitor and first catalyst to obtain hydroxyl-terminated itaconic acid diol oligomer.

[0048] A second mixed reaction system containing itaconic acid diol oligomer, polyester diol, diisocyanate, solvent and a second catalyst is subjected to microwave prepolymerization reaction, and then a straight-chain diol is added to continue the chain extension reaction to obtain a biodegradable medical itaconic acid polyurethane material.

[0049] In some more specific preferred embodiments, the preparation method of the biodegradable medical itaconic acid polyurethane material includes the following steps:

[0050] Step 1: Mix itaconic acid with short-chain diol, add polymerization inhibitor and first catalyst, and prepare hydroxyl-terminated itaconic acid diol oligomer through a two-step method of esterification and polycondensation, and then dry it.

[0051] Step 2: Polyester glycol is added to the itaconic acid diol oligomer dried in Step 1 as a binary soft segment structure system. At the same time, diisocyanate, solvent and second catalyst are added. After microwave prepolymerization for a period of time, straight-chain diol is added to continue the chain extension reaction to obtain the biodegradable medical itaconic acid polyurethane material.

[0052] In some implementations, in step 1, the short-chain diol may include any one or a combination of two or more of 1,2-ethylene glycol, 1,3-propanediol, 1,4-butanediol, 1,5-pentanediol, and 1,6-hexanediol, but is not limited thereto.

[0053] The itaconic acid diol oligomer of the present invention is prepared by solvent-free melt polycondensation.

[0054] In some implementations, in step 1, the polymerization inhibitor may include any one or a combination of two or more of 4-methoxyphenol, hydroquinone, o-methylhydroquinone, p-hydroxyanisole, etc., but is not limited thereto.

[0055] Furthermore, in step 1, the first catalyst may include any one or a combination of two or more of stannous chloride dihydrate, p-benzenesulfonic acid hydrate, zinc acetate dihydrate, etc., but is not limited to this.

[0056] In some implementation schemes, in step 1, the molar ratio of itaconic acid to short-chain diol is in the range of 1:1.1 to 1:1.3.

[0057] Furthermore, the amount of the polymerization inhibitor is 0.4% to 0.8% of the molar amount of itaconic acid.

[0058] Furthermore, the amount of the first catalyst is 0.1 to 0.3% of the molar amount of itaconic acid.

[0059] In some implementation schemes, in step 1, the temperature of the esterification reaction is 120–150°C, and the reaction time is 8–10 hours.

[0060] In some implementation schemes, in step 1, the temperature of the polycondensation reaction is 170–180°C, and the reaction time is 1–4 hours.

[0061] In some implementations, in step 2, the polyester diol may include any one or a combination of two or more of polycaprolactone diol, polyethylene glycol, and polyhexyl adipate, but is not limited thereto. The polyester diol is preferably polycaprolactone diol, which, together with itaconic acid diol oligomers, serves as the binary soft segment structural portion of the polyurethane backbone.

[0062] Furthermore, the number-average molecular weight of the polyester diol is 500 to 2000.

[0063] In some embodiments, step 2 may include, but is not limited to, any one or a combination of two or more of diphenylmethane diisocyanate, isophorone diisocyanate, terephthalic diisocyanate, 1,5-naphthalene diisocyanate, toluene diisocyanate, and dicyclohexyl diisocyanate. The diisocyanate is preferably diphenylmethane diisocyanate, toluene diisocyanate, etc.

[0064] In some embodiments, the amount of isocyanate is calculated based on the hydroxyl content of a mixture of itaconic acid glycol oligomer, polyester glycol, and linear diol, and the total isocyanate index of the system is 1.05 to 1.10.

[0065] In some implementations, in step 2, the straight-chain diol may include any one or a combination of two or more of 1,3-propanediol, 1,4-butanediol, 1,5-pentanediol, and 1,6-hexanediol, but is not limited thereto.

[0066] Furthermore, the solvent may include, but is not limited to, N,N-dimethylformamide.

[0067] In some embodiments, in step 2, the second catalyst may include amine compounds and / or organometallic compounds, preferably including but not limited to any one or a combination of two or more of dibutyltin dilaurate, stannous octoate, and stannous isooctanoate.

[0068] In some implementation schemes, in step 2, the molar ratio of the itaconic acid diol oligomer to the polyester diol is in the range of 1:2 to 2:1.

[0069] Furthermore, the amount of the second catalyst is 1% to 2% of the total mass of the second mixed reaction system.

[0070] In some implementation schemes, in step 2, the mass ratio of the combination of linear diol and diisocyanate to the combination of itaconic acid diol oligomer and polyester diol is 5:5 to 7:3. In other words, the mass ratio of linear diol as chain extender and diisocyanate as hard segment structure to soft segment structure (itaconic acid diol oligomer and polyester diol) is in the range of 5:5 to 7:3.

[0071] In some implementation schemes, in step 2, the temperature of the microwave prepolymerization reaction is 60-70°C, and the time of the microwave prepolymerization reaction is 20-40 minutes.

[0072] In some implementation schemes, in step 2, the temperature of the chain extension reaction is 60-80°C, and the reaction time is 40-70 min.

[0073] Considering the performance of the polyurethane product, this invention uses a stepwise method instead of a one-pot method to prepare the biodegradable medical itaconic acid polyurethane material.

[0074] In the process of preparing biodegradable medical itaconic acid polyurethane materials, hydroxyl-terminated itaconic acid diol oligomers, polyester diols, and linear diols all need to be dehydrated before the reaction.

[0075] As one aspect of the technical solution of the present invention, it involves a biodegradable medical itaconic acid polyurethane material prepared by the aforementioned preparation method.

[0076] Furthermore, this invention uses itaconic acid diol oligomers as the soft segment structure of polyurethane. Degradation and biological experiments have demonstrated that the prepared itaconic acid polyurethane material has degradability, excellent mechanical properties, stable thermodynamic properties, and good biocompatibility.

[0077] As one aspect of the technical solution of the present invention, it relates to the application of the aforementioned biodegradable medical itaconic acid polyurethane material in the preparation of medical implants.

[0078] Furthermore, the medical implant may be a vascular graft tubular object, but is not limited to this.

[0079] The itaconic acid polyurethane material prepared by this invention has comprehensive performance comparable to that of pure commercial soft segment polyurethane material, and the material has an appropriate contact angle size that can reduce adverse reactions such as bioadhesion. This invention proposes a new strategy for biodegradable medical implant polyurethane material.

[0080] As one aspect of the technical solution of the present invention, it relates to a method for preparing a vascular transplant tubular object, which includes: preparing a small-diameter vascular transplant tubular object by electrospinning the biodegradable medical itaconic acid polyurethane material.

[0081] Specifically, the process conditions for the electrospinning technology include: a spinning solution concentration of 20-30%, a voltage of 12-17KV, a receiver distance of 12-18cm, and an injection rate of 0.8-1.2mL / h.

[0082] In summary, this invention utilizes the active carboxyl group structure of bio-based itaconic acid to synthesize hydroxyl-terminated itaconic acid diol oligomers, which, together with polyester diol as the soft segment structure of polyurethane, produce itaconic acid polyurethane materials with degradable properties, excellent mechanical properties, stable thermodynamics, and good biocompatibility.

[0083] To make the objectives, technical solutions, and advantages of this invention clearer, the invention will be further described in detail below with reference to embodiments. It should be understood that the specific embodiments described herein are merely illustrative and not intended to limit the invention. Modifications or equivalent substitutions made by those skilled in the art based on their understanding of the technical solutions of this invention, without departing from the spirit and scope of the invention, should be covered within the protection scope of this invention.

[0084] All raw materials used in the following specific implementation methods were purchased from the market.

[0085] Example 1

[0086] Step 1: Weigh 65.1 g (0.5 mol) itaconic acid and 50.7 g (0.56 mol) 1,4-butanediol into a three-necked flask. Simultaneously add 0.24 g (0.5% mol relative to itaconic acid) of hydroquinone as a polymerization inhibitor to protect the double bonds, and 0.2 g (0.16% mol relative to itaconic acid) of SnCl2·2H2O as the first catalyst. Purge with nitrogen, attach a stir bar and condenser, and esterify at 150°C for 10 h. Then remove the condenser and nitrogen, and condense under vacuum at 180°C for 2-3 h. Dissolve the crude product in chloroform, precipitate the oligomers with a large amount of methanol or ethanol, allow to stand and separate the layers, then rotary evaporate the lower layer to remove the solvent, thus obtaining the itaconic acid-butanediol oligomer. The synthesis process and product structure are as follows. Figure 1 As shown.

[0087] Step 2, weigh 3.13g of itaconic acid butylene glycol oligomer and 4.5g of polycaprolactone diol (n IABDo :n PCLThe mixture (1:2) was placed in a straight-necked three-necked flask as a di-polyol structure (for the mono-soft segment structure, only one diol was weighed out), and 6.42g of diphenylmethane diisocyanate was used as the hard segment structure of the polyurethane, with an isocyanate index of 1.1. Simultaneously, 70-80g of N,N-dimethylformamide was added as the reaction solvent and 0.09g of dibutyltin dilaurate as the second catalyst. The straight-necked three-necked flask was then placed in a microwave reactor, purged with nitrogen, and equipped with a mechanical stirrer and reflux condenser. The prepolymerization reaction was carried out at 60℃ for 30 min, followed by the addition of 1.21g of 1,3-propanediol, and a chain extension reaction was performed at 70℃ for 50 min. After the reaction was complete, the reaction solution was poured into a PTFE plate or petri dish and placed on a 70℃ hot plate to evaporate the solvent, forming a biodegradable medical itaconic acid polyurethane material. The synthesis process and product structure are as follows. Figure 2 As shown, its infrared spectrum is as follows Figure 5 As shown.

[0088] The prepared itaconic acid polyurethane material was cut into dumbbell-shaped tensile specimens and tested using a universal tensile testing machine according to international standard ISO 527-1:2012. The results showed that... Figure 3 As shown, the itaconic acid polyurethane material prepared in this embodiment has a tensile modulus of 37.8 MPa, a tensile strength of 33.8 MPa, and an elongation at break of 480%, while also exhibiting good biocompatibility.

[0089] In this embodiment, the Masson and H&E staining images of the tissue 30 days after implantation of the biodegradable medical itaconic acid polyurethane material are as follows: Figure 4a and Figure 4b As shown.

[0090] Example 2

[0091] The preparation method of Example 1 was followed, except that the ratio of hard segment Hs (total mass of isocyanate and linear diol): soft segment Ss (total mass of itaconic acid oligomer and polyester diol) = 5:5 was replaced with Hs:Ss = 6:4, resulting in itaconic acid polyurethane material. After testing its various properties using the same method, it was found that the prepared itaconic acid polyurethane material has a tensile modulus of 25.6 MPa, a tensile strength of 22.9 MPa, and an elongation at break of 460%, while also exhibiting good biocompatibility. Figure 6 This is a schematic diagram illustrating the biodegradability of the biodegradable medical itaconic acid polyurethane material prepared in this embodiment.

[0092] Example 3

[0093] The preparation method of Example 1 was followed, except that the ratio of hard segment Hs (total mass of isocyanate and linear diol): soft segment Ss (total mass of itaconic acid oligomer and polyester diol) = 5:5 was replaced with Hs:Ss = 7:3, resulting in itaconic acid polyurethane material. After testing its various properties using the same method, it was found that the prepared itaconic acid polyurethane material has a tensile modulus of 16.4 MPa, a tensile strength of 9 MPa, and an elongation at break of 340%, while also exhibiting good biocompatibility.

[0094] Example 4

[0095] The preparation method of Example 1 was followed, except that 1 part of itaconic acid diol oligomer was replaced with 2 parts to obtain itaconic acid polyurethane material. Its various properties were tested by the same method as above and it was found that the prepared itaconic acid polyurethane material has a tensile modulus of 30.5 MPa, a tensile strength of 31.9 MPa, and an elongation at break of 500%, and also has good biocompatibility.

[0096] Example 5

[0097] The preparation method of Example 1 was followed, except that 1 part of N,N-dimethylformamide solvent was replaced with 0.5 parts to obtain itaconic acid polyurethane material. Its various properties were tested by the same method as above and it was found that the prepared itaconic acid polyurethane material has a tensile modulus of 34.2 MPa, a tensile strength of 33.5 MPa, and an elongation at break of 500%, and also has good biocompatibility.

[0098] Example 6

[0099] The preparation method of Example 1 was followed, except that 1 part of N,N-dimethylformamide solvent was replaced with 1.2 parts to obtain itaconic acid polyurethane material. Its various properties were tested by the same method as above and it was found that the prepared itaconic acid polyurethane material has a tensile modulus of 27.2 MPa, a tensile strength of 25.4 MPa, and an elongation at break of 460%, and also has good biocompatibility.

[0100] Example 7

[0101] The preparation method of Example 1 was followed, except that 1,4-butanediol in the first step was replaced with 1,6-hexanediol, the molar ratio of itaconic acid to 1,6-hexanediol was 1:1.1, the amount of polymerization inhibitor accounted for 0.4% of the molar amount of itaconic acid, the amount of the first catalyst SnCl2·2H2O accounted for 0.1% of the molar amount of itaconic acid, the esterification reaction was carried out at 120℃ for 9 hours, and the condensation reaction was carried out at 170℃ under vacuum for 4 hours to obtain itaconic acid polyurethane material. After testing its various properties using the same method, it was found that the prepared itaconic acid polyurethane material had a tensile modulus of 28.4 MPa, a tensile strength of 26.9 MPa, and an elongation at break of 530%, and also had good biocompatibility.

[0102] Example 8

[0103] The preparation method of Example 1 was followed, except that the polymerization inhibitor in the first step was changed to 4-methoxyphenol, the molar ratio of itaconic acid to 1,6-hexanediol was 1:1.3, the amount of polymerization inhibitor accounted for 0.8% of the molar amount of itaconic acid, the amount of the first catalyst SnCl2·2H2O accounted for 0.3% of the molar amount of itaconic acid, the esterification reaction was carried out at 140℃ for 8 hours, and the condensation reaction was carried out at 175℃ under vacuum for 1 hour to obtain itaconic acid polyurethane material. The properties of the prepared itaconic acid polyurethane material were tested by the same method as above and it was found that the tensile modulus of the prepared itaconic acid polyurethane material was 24.3 MPa, the tensile strength was 21.8 MPa, the elongation at break was 460%, and it also had good biocompatibility.

[0104] Example 9

[0105] The preparation method of Example 1 was followed, except that the SnCl2·2H2O catalyst in the first step was replaced with p-benzenesulfonic acid hydrate to obtain itaconic acid polyurethane material. Its various properties were tested by the same method as above and it was found that the prepared itaconic acid polyurethane material has a tensile modulus of 25.8 MPa, a tensile strength of 27.3 MPa, and an elongation at break of 550%, and also has good biocompatibility.

[0106] Example 10

[0107] The preparation method of Example 1 is followed, except that the isocyanate in the second step is replaced with dicyclohexyl diisocyanate to obtain itaconic acid polyurethane material. Its various properties are tested by the same method as above. It is found that the prepared itaconic acid polyurethane material has a tensile modulus of 14.9 MPa, a tensile strength of 16.2 MPa, and an elongation at break of 490%, and also has good biocompatibility.

[0108] Example 11

[0109] The preparation method of Example 1 was followed, except that the linear diol in the second step was replaced with 1,4-butanediol, the molar ratio of itaconic acid diol oligomer to polycaprolactone diol was 2:1, the second catalyst was tin isooctanoate, and the amount of the second catalyst was 2% of the total mass of the second mixed reaction system. Itaconic acid polyurethane material was obtained. Its various properties were tested by the same method as above. It was found that the prepared itaconic acid polyurethane material had a tensile modulus of 28.6 MPa, a tensile strength of 30.2 MPa, and an elongation at break of 520%, and also had good biocompatibility.

[0110] Example 12

[0111] The preparation method of Example 1 was followed, except that the isocyanate index in the second step was changed to 1.05 to obtain itaconic acid polyurethane material. Its various properties were tested by the same method as above and it was found that the prepared itaconic acid polyurethane material has a tensile modulus of 26.2 MPa, a tensile strength of 23.8 MPa, and an elongation at break of 440%, and also has good biocompatibility.

[0112] Example 13

[0113] The preparation method of Example 1 was followed, except that the second catalyst in the second step was changed to stannous octoate, and the amount was 1% of the total mass of the second mixed reaction system. The microwave prepolymerization reaction was carried out at 70°C for 20 min, and the chain extension reaction was carried out at 80°C for 40 min to obtain itaconic acid polyurethane material. Its various properties were tested by the same method as above and it was found that the prepared itaconic acid polyurethane material had a tensile modulus of 30.1 MPa, a tensile strength of 32.9 MPa, and an elongation at break of 520%, and also had good biocompatibility.

[0114] Example 14

[0115] The preparation method of Example 1 was followed, except that the polyester glycol in the second step was replaced with polyethylene glycol. The product underwent microwave prepolymerization at 65°C for 40 min and chain extension reaction at 60°C for 70 min to obtain itaconic acid polyurethane material. Its various properties were tested using the same method as above, and it was found that the prepared itaconic acid polyurethane material has a tensile modulus of 22.6 MPa, a tensile strength of 21.5 MPa, and an elongation at break of 450%, while also exhibiting good biocompatibility.

[0116] Comparative Example 1

[0117] The difference between this comparative example and the preparation method of Example 1 is that: n IABDo :n PCL =1:2 replaced with n IABDo :n PCL=1:3, itaconic acid polyurethane was obtained. Its various properties were tested using the same method as above. It was found that itaconic acid polyurethane has a tensile modulus of 12MPa, a tensile strength of 14.3MPa, and an elongation at break of 280%. The mechanical properties were lower than those in Example 1. The reason is that the difference in the proportion of components between polycaprolactone and itaconic acid oligomer is too large, which affects the arrangement of molecular chain segments.

[0118] Comparative Example 2

[0119] The difference between this comparative example and the preparation method of Example 1 is that: n IABDo :n PCL =1:2 replaced with n IABDo :n PCL The ratio of itaconic acid to polyurethane was 3:1. Its properties were tested using the same method as above. Itaconic acid polyurethane exhibited a tensile modulus of 9.8 MPa, a tensile strength of 11.3 MPa, and an elongation at break of 210%. The mechanical properties were lower than those of Example 1. This is because the itaconic acid oligomer has a side double bond structure compared to polycaprolactone diol, which increases steric hindrance. Excessive itaconic acid components can affect the connection and entanglement of molecular chains.

[0120] Comparative Example 3

[0121] The difference between this comparative example and the preparation method of Example 1 is that: based on n IABDo :n PCL =1:2 replaced with n IABDO :n PCL The ratio of polycaprolactone to itaconic acid oligomer was 1:4. After testing its various properties using the same method, itaconic acid polyurethane was found to have a tensile modulus of 8.9 MPa. This is because the large difference in the ratio of polycaprolactone to itaconic acid oligomer affects the arrangement of molecular chain segments.

[0122] Comparative Example 4

[0123] The difference between this comparative example and the preparation method of Example 1 is that the binary soft segment structure was replaced with a single itaconic acid oligomer to obtain itaconic acid polyurethane. After testing its various properties using the same method, itaconic acid polyurethane was found to have a tensile modulus of 12.1 MPa, a tensile strength of 18.8 MPa, and an elongation at break of 330%. The mechanical properties are lower than those of Example 1. This is because the itaconic acid oligomer has a side double bond structure compared to polycaprolactone diol, which increases steric hindrance and affects the connection and entanglement of molecular chains.

[0124] Application examples

[0125] Weigh 5g of the polyurethane film prepared in Example 1, cut it into small pieces, place it in a transparent sample bottle, add 9.3g of DMF, stir at 70℃ for 2h, and prepare an electrospinning solution with a concentration of 25-35%. The spinning parameters are: voltage range of 10KV-16KV, flow rate of 0.9-1ml / h, receiver roller speed of 285 rpm, and spinning receiving distance of 15-20cm, to prepare a vascular graft tubular structure.

[0126] In addition, the inventors of this case also conducted experiments with other raw materials and conditions listed in this specification, referring to the aforementioned embodiments, and similarly obtained a biodegradable medical itaconic acid polyurethane material with degradable properties, excellent mechanical properties, stable thermodynamics and good biocompatibility.

[0127] The technical features of the above embodiments can be combined in any way. For the sake of brevity, not all possible combinations of the technical features in the above 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.

[0128] The embodiments described above are merely examples of several implementations of the present invention, and while the descriptions are relatively specific and detailed, they should not be construed as limiting the scope of the invention. It should be noted that those skilled in the art can make various modifications and improvements without departing from the concept of the present invention, and these modifications and improvements all fall within the scope of protection of the present invention.

Claims

1. A method for preparing a biodegradable medical itaconic acid polyurethane material, characterized in that, include: A first mixed reaction system comprising itaconic acid, a short-chain diol, a polymerization inhibitor, and a first catalyst is subjected to esterification and polycondensation reactions to obtain hydroxyl-terminated itaconic acid diol oligomers. The short-chain diol is selected from any one or a combination of two or more of 1,2-ethylene glycol, 1,3-propanediol, 1,4-butanediol, 1,5-pentanediol, and 1,6-hexanediol. The polymerization inhibitor is selected from any one or a combination of two or more of 4-methoxyphenol, hydroquinone, o-methylhydroquinone, and p-hydroxyanisole. The molar ratio of itaconic acid to the short-chain diol is 1:1.1 to 1:1.

3. The esterification reaction is carried out at a temperature of 120-150°C for 8-10 hours. The polycondensation reaction is carried out at a temperature of 170-180°C for 1-4 hours. A microwave prepolymerization reaction is carried out on a second mixed reaction system comprising itaconic acid diol oligomer, polyester diol, diisocyanate, solvent, and a second catalyst. Then, a linear diol is added to continue the chain extension reaction, yielding a biodegradable medical itaconic acid polyurethane material. The polyester diol is selected from any one or a combination of two or more of polycaprolactone diol, polyethylene glycol, and polyhexyl adipate. The linear diol is selected from any one or a combination of two or more of 1,3-propanediol, 1,4-butanediol, 1,5-pentanediol, and 1,6-hexanediol. The diisocyanate is selected from diphenylmethane diisocyanate and isoflavone diisocyanate. The product comprises any one or a combination of two or more of the following: ketone diisocyanate, terephthalic diisocyanate, 1,5-naphthalene diisocyanate, toluene diisocyanate, and dicyclohexyl diisocyanate; the molar ratio of the itaconic acid diol oligomer to the polyester diol is 1:2 to 2:1, and the mass ratio of the combination of the linear diol and diisocyanate to the combination of the itaconic acid diol oligomer and the polyester diol is 5:5 to 7:3; the microwave prepolymerization reaction temperature is 60 to 70°C, and the microwave prepolymerization reaction time is 20 to 40 minutes; the chain extension reaction temperature is 60 to 80°C, and the chain extension reaction time is 40 to 70 minutes. The biodegradable medical itaconic acid polyurethane material has the structure shown in formula (I): ； Equation (I); Wherein, R1 is the residue of the itaconic acid diol oligomer prepared from itaconic acid and short-chain diol; R2 is the residue of polyester diol; D is the residue of diisocyanate; B is the residue of linear diol; and n is a positive integer from 5 to 12.

2. The preparation method according to claim 1, characterized in that: The number-average molecular weight of the polyester diol is 500-2000.

3. The preparation method according to claim 1, characterized in that: The biodegradable medical itaconic acid polyurethane material includes soft segments containing residues of itaconic acid diol oligomers and polyester diol residues, and hard segments containing residues of diisocyanate and linear diol residues; the content of soft segments in the biodegradable medical itaconic acid polyurethane material is 50~70wt%.

4. The preparation method according to claim 3, characterized in that: The mass percentage of itaconic acid diol oligomer in the soft segment is 25% to 65%.

5. The preparation method according to claim 1, characterized in that: The biodegradable medical itaconic acid polyurethane material has a tensile modulus of 5~80MPa, a tensile strength of 8.0~33.8MPa, and an elongation at break of 170~500%.

6. The preparation method according to claim 1, characterized in that: The first catalyst is selected from any one or a combination of two or more of stannous chloride dihydrate, p-benzenesulfonic acid hydrate, and zinc acetate dihydrate.

7. The preparation method according to claim 1, characterized in that: The amount of the polymerization inhibitor is 0.4-0.8% of the molar amount of itaconic acid.

8. The preparation method according to claim 1, characterized in that: The amount of the first catalyst is 0.1 to 0.3% of the molar amount of itaconic acid.

9. The preparation method according to claim 1, characterized in that: The solvent is N,N-dimethylformamide.

10. The preparation method according to claim 1, characterized in that: The second catalyst is selected from any one or a combination of two or more of dibutyltin dilaurate, stannous octoate, and stannous isooctanoate.

11. The preparation method according to claim 1, characterized in that: The amount of the second catalyst is 1% to 2% of the total mass of the second mixed reaction system.

12. The preparation method according to claim 1, characterized in that: The amount of diisocyanate used is calculated based on the hydroxyl content of the mixture of itaconic acid diol oligomer, polyester diol and linear diol, with an isocyanate index of 1.05 to 1.

10.

13. A biodegradable medical itaconic acid polyurethane material prepared by any one of claims 1-12.

14. The application of the biodegradable medical itaconic acid polyurethane material of claim 13 in the preparation of medical implants, wherein the medical implant is a vascular transplant tubular structure.

15. A method for preparing a tubular vascular graft, characterized in that, include: The biodegradable medical itaconic acid polyurethane material of claim 13 is used to prepare a vascular transplant tubular material by electrospinning technology.

16. The preparation method according to claim 15, characterized in that, The process conditions for the electrospinning technology include: a spinning solution concentration of 20-30%, a voltage of 12-17KV, a receiver distance of 12-18cm, and an injection rate of 0.8-1.2mL / h.

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