Degradable polyurethane and preparation method and application thereof

Abstract

The application belongs to the technical field of polyurethane, and relates to a kind of polyurethane material and its preparation method and application.The biodegradable polyurethane has the structure shown in formula (1).The polyurethane provided by the application has controllable degradation performance and excellent mechanical properties to meet the use requirements of different application scenarios.

Description

Technical Field

[0001] This invention belongs to the field of polyurethane technology, and relates to a polyurethane material, its preparation method, and its application. Background Technology

[0002] With the rapid development of the plastics industry, plastics are being used more and more widely in various industries and fields. Simultaneously, the biodegradability of plastics is receiving increasing attention, as biodegradable plastic products can reduce environmental pollution and promote sustainable environmental development. Thermoplastic polyurethane elastomers (TPUs) have been widely used in numerous fields due to their high strength, high wear resistance, wide hardness range, and wide processing temperature. Currently, the annual consumption of polyurethane elastomers reaches 20 million tons. However, polyurethane elastomers are not easily degraded in nature and are difficult to recycle. At the end of their service life, they are often disposed of through incineration or landfill, posing environmental pollution problems. Therefore, adhering to the concept of green and environmentally friendly development, the biodegradability of polyurethane elastomers and the bio-based sourcing of raw materials have received widespread attention from academia and industry.

[0003] Typical linear TPU is a multi-block thermoplastic elastomer formed by the reaction of polymeric diols, diisocyanates, and small-molecule diols or diamines. Based on the mobility of the chain segments, the microphase formed by the polymeric diol is generally called the soft segment, which imparts elasticity to the polyurethane; the microphase formed by the isocyanate and the small-molecule diol or diamine is called the hard segment, which provides mechanical strength to the polyurethane.

[0004] Currently, research on the development of biodegradability of TPU mainly involves replacing the soft segment components with biodegradable polymer polyols, such as vegetable oil-based polyols and polyester polyols. CN116355174A uses a polycarbonate-degradable polyol as the soft segment, but the presence of a benzene ring structure in the main chain leads to potential biotoxicity and a long degradation cycle. CN113968954A introduces polylactic acid / polybutylene terephthalate / polyester polyol blocks into the polyester polyol system, enabling rapid degradation of the TPU soft segment; however, products obtained using this method generally have low elongation at break, limiting their application in some areas. CN117510774A synthesized a polyurethane based on PGA glycol and PPC glycol, but the degradation rate of the final synthesized product was uncontrollable. In summary, the degradation rate of soft segment biodegradable TPU has a very limited adjustable range, making it difficult to meet the needs of practical applications such as drug release, plastic surgery, and tissue engineering. In particular, it is difficult to achieve the goal of flexibly controlling the degradation rate over a wide range to match different tissue growth rates.

[0005] The improvement of hard segment degradation rate is mainly achieved by selecting small molecule chain extenders containing easily degradable groups or degradable diisocyanates. CN113195197A designed a chain extender with degradable groups for polyurethanes with a high hard segment content (30-60%), but did not explicitly control the degradation rate. CN113603852A synthesized undecenoic acid diol and undecenoic acid diol chain extenders with different dangling chain lengths. The polyurethane prepared by reacting the chain extender with polyol as a raw material contains dangling chains, which reduces the crystallinity of polyurethane and thus improves degradation efficiency, but the mechanical strength of the corresponding polyurethane material is low. CN108059706A synthesized polycaprolactone-based polyurethane using lysine diisocyanate, but while imparting hard segment degradability, it often leads to damage to mechanical properties, thermal stability, and biocompatibility. Therefore, how to achieve a balance between the degradation performance and mechanical properties and other properties of polyurethane materials, and endow polyurethanes with good mechanical properties and flexibly controllable degradation performance, remains an urgent problem to be solved. Summary of the Invention

[0006] The present invention aims to provide a polyurethane material with controllable degradation performance and excellent mechanical properties, as well as its preparation method and application.

[0007] In a first aspect, the biodegradable polyurethane provided by the present invention has the structure shown in formula (1):

[0008]

[0009] R1 is derived from isocyanate; R2 is derived from polyglycolic acid polyol or a composition of polyglycolic acid polyol with a small molecule diol and / or a small molecule diamine, wherein the number average molecular weight of the polyglycolic acid polyol is less than 3000 Da; R3 is derived from macromolecular polyol, wherein the macromolecular polyol is selected from at least one of polyester polyol, polyether polyol and polycarbonate polyol with a number average molecular weight of 1 kDa to 8 kDa; n ≥ 1.

[0010] Secondly, the method for preparing biodegradable polyurethane provided by the present invention includes the following steps:

[0011] S1. A nucleophilic addition reaction is carried out between isocyanate and macromolecular polyol, wherein the macromolecular polyol is selected from at least one of polyester polyol, polyether polyol and polycarbonate polyol with a number average molecular weight of 1kDa to 8kDa, to obtain a polyurethane prepolymer with isocyanate-terminated ends.

[0012] S2. The polyurethane prepolymer is subjected to a chain extension reaction using polyglycolic acid polyol or a combination of polyglycolic acid polyol with small molecule diol and / or small molecule diamine as a chain extender to obtain biodegradable polyurethane.

[0013] Thirdly, the present invention provides the application of the above-mentioned biodegradable polyurethane in the medical and packaging fields.

[0014] The key to this invention lies in selecting macromolecular polyols with specific molecular weights as the soft segments of polyurethane, and employing a two-step method (prepolymer method) to first end-cap the macromolecular polyols with isocyanate, followed by a chain extension reaction using a chain extender containing polyglycolic acid polyol. This alters the chemical composition and structure of the polyurethane, resulting in a more ordered and regular polyurethane structure. Simultaneously, the degradable segments are located in the hard segments of the polyurethane and are uniformly distributed within them. This precise segmentation and arrangement of soft and hard segments allows for customized polyurethane design, effectively controlling its degradation rate. This endows the polyurethane with controllable degradation performance and excellent mechanical properties to meet the needs of various application scenarios. Furthermore, the biodegradable polyurethane characteristics provided by this invention are particularly advantageous for developing materials that can partially, completely, or nearly completely degrade within a specific timeframe, especially suitable for scenarios requiring degradation treatment after the functional failure of polyurethane materials. Attached Figure Description

[0015] Figure 1 The images show the proton NMR spectra of the biodegradable polyurethanes synthesized in Examples 1-4 and the polyurethane synthesized in Comparative Example 1.

[0016] Figure 2 The degradation curves are shown for the biodegradable polyurethanes synthesized in Examples 1-4 and the polyurethanes synthesized in Comparative Examples 1-2.

[0017] Figure 3 The degradation curves are for the biodegradable polyurethanes synthesized in Examples 1 and 7, and the polyurethanes synthesized in Comparative Examples 1 and 3.

[0018] Figure 4 The images show the 1H NMR spectra of the biodegradable polyurethane synthesized in Example 1 and the residues of the polyurethane synthesized in Comparative Example 1 after long-term degradation.

[0019] Figure 5 The GPC curves are shown for the pre-degradation products and long-term degradation residues of the biodegradable polyurethane synthesized in Example 1 and the polyurethane synthesized in Comparative Example 1.

[0020] Figure 6 The images show the pre-degradation products and long-term degradation residues of the biodegradable polyurethane synthesized in Example 1 and the polyurethane synthesized in Comparative Example 1, as well as the DSC curves of the polycaprolactone diol used during the first cooling and second heating cycles. Detailed Implementation

[0021] The biodegradable polyurethane provided by this invention has the structure shown in formula (1):

[0022]

[0023] R1 is derived from isocyanate; R2 is derived from polyglycolic acid polyol or a composition of polyglycolic acid polyol with a small molecule diol and / or a small molecule diamine, wherein the number average molecular weight of the polyglycolic acid polyol is less than 3000 Da; R3 is derived from macromolecular polyol, wherein the macromolecular polyol is selected from at least one of polyester polyol, polyether polyol and polycarbonate polyol with a number average molecular weight of 1 kDa to 8 kDa; n ≥ 1.

[0024] In this invention, R1 originates from isocyanate, that is, the residue formed at the isocyanate end after a nucleophilic addition reaction between an isocyanate and a macromolecular polyol. The type of isocyanate is not particularly limited and can be any existing isocyanate compound with a functionality of 2 or higher, including but not limited to at least one of hexamethylene diisocyanate (HDI), lysine diisocyanate (LDI), toluene diisocyanate (TDI), diphenylmethane diisocyanate (MDI), isophorone diisocyanate (IPDI), and 4,4'-dicyclohexylmethane diisocyanate (HMDI).

[0025] In this invention, R2 originates from polyglycolic acid polyol or a composition of polyglycolic acid polyol with a small molecule diol and / or a small molecule diamine, that is, from the residues formed at the end of the chain extender after the reaction of the chain extender (polyglycolic acid polyol or a composition of polyglycolic acid polyol with a small molecule diol and / or a small molecule diamine) and isocyanate. Specifically, R2 can be entirely derived from polyglycolic acid polyol, partially derived from polyglycolic acid polyol with the remainder derived from a small molecule diol, partially derived from polyglycolic acid polyol with the remainder derived from a small molecule diamine, or partially derived from polyglycolic acid polyol with the remainder derived from a composition of a small molecule diol and a small molecule diamine. Furthermore, the molar percentage of polyglycolic acid polyols in R2 is preferably 20%–100%, such as 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 100%, or any value between them. Here, molar percentage refers to the proportion of the molar amount of polyglycolic acid polyols in R2 to the total molar amount of polyglycolic acid polyols, small molecule diols, and small molecule diamines. When the proportion of polyglycolic acid polyols in R2 is controlled between 20% and 100%, the resulting polyurethane exhibits better degradation performance.

[0026] In this invention, the number-average molecular weight of the polyglycolic acid polyol is below 3000 Da, more preferably below 2000 Da, even more preferably below 1500 Da, more preferably below 1000 Da, and most preferably between 200 and 500 Da. Specifically, it can be 200 Da, 250 Da, 300 Da, 350 Da, 400 Da, 450 Da, 500 Da, or any value between them. The inventors of this invention have discovered that when the number-average molecular weight of the polyglycolic acid polyol is controlled below 3000 Da, the microstructure of the polyurethane can be effectively controlled, allowing it to be uniformly embedded in the hard segment structure of the polyurethane, thereby endowing the polyurethane with controllable degradation performance and excellent mechanical properties. When the number-average molecular weight of the polyglycolic acid polyol is controlled between 200 and 500 Da, the degradation rate is faster and the mechanical property enhancement effect is better.

[0027] In this invention, the type of small molecule diol is not particularly limited, but is preferably a C2 to C5 diol, specifically including at least one of ethylene glycol, propylene glycol and butanediol.

[0028] In this invention, the type of small molecule diamine is not particularly limited, but is preferably a C2 to C5 diamine, such as at least one of ethylenediamine, propylenediamine and butanediamine.

[0029] In this invention, R3 originates from a macromolecular polyol, specifically a residue formed at the end of the macromolecular polyol after a nucleophilic addition reaction between the macromolecular polyol and an isocyanate. The macromolecular polyol is selected from at least one of polyester polyols, polyether polyols, and polycarbonate polyols. Compared to polyurethanes where R3 originates from other polyols, the mechanical properties of the resulting polyurethane are significantly improved when R3 originates from a flexible polyester polyol such as polycaprolactone polyol or polybutylene adipate polyol. The number-average molecular weight of the macromolecular polyol is 1 kDa to 8 kDa, such as 1 kDa, 2 kDa, 3 kDa, 4 kDa, 5 kDa, 6 kDa, 7 kDa, 8 kDa, or any value between them.

[0030] In this invention, n ≥ 1, and can specifically be 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 100, etc. Furthermore, the number-average molecular weight of the biodegradable polyurethane is preferably 10 kDa to 100 kDa, such as 10 kDa, 15 kDa, 20 kDa, 25 kDa, 30 kDa, 35 kDa, 40 kDa, 45 kDa, 50 kDa, 55 kDa, 60 kDa, 65 kDa, 70 kDa, 75 kDa, 80 kDa, 85 kDa, 90 kDa, 95 kDa, 100 kDa, or any value between them.

[0031] The biodegradable polyurethane provided by this invention can degrade at 20–45°C. The degradation time of the biodegradable polyurethane is preferably less than 36 months, more preferably less than 24 months, more preferably less than 12 months, more preferably less than 6 months, and most preferably less than 3 months. Under the conditions of ASTM F1635, the mass loss of the biodegradable polyurethane after 12 months of degradation at 20–45°C is generally greater than 20%, for example, it can be 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, or any value between them.

[0032] The biodegradable polyurethane obtained by using a component containing polyglycolic acid polyol as a chain extender provided by the present invention has a higher ultimate tensile strength than polyurethane obtained by using a component without polyglycolic acid polyol as a chain extender. The ratio of the two is preferably 50% or more, more preferably 100% or more, more preferably 150% or more, more preferably 200% or more, more preferably 350% or more, more preferably 400% or more, more preferably 450% or more, and most preferably 500% or more.

[0033] The method for preparing biodegradable polyurethane provided by this invention includes the following steps:

[0034] S1. A nucleophilic addition reaction is carried out between isocyanate and macromolecular polyol to obtain a polyurethane prepolymer with isocyanate-terminated ends;

[0035] S2. The polyurethane prepolymer is subjected to a chain extension reaction using polyglycolic acid polyol or a combination of polyglycolic acid polyol with small molecule diol and / or small molecule diamine as a chain extender to obtain biodegradable polyurethane.

[0036] In this invention, the macromolecular polyol is selected from at least one of polyester polyols, polyether polyols, and polycarbonate polyols. The number-average molecular weight of the macromolecular polyol is 1 kDa to 8 kDa, such as 1 kDa, 2 kDa, 3 kDa, 4 kDa, 5 kDa, 6 kDa, 7 kDa, 8 kDa, or any value between them.

[0037] In this invention, in step S1, the molar ratio of isocyanate in the isocyanate to hydroxyl in the macromolecular polyol is preferably (1.1 to 2.5):1, such as 1.1:1, 1.3:1, 1.5:1, 1.7:1, 1.9:1, 2.1:1, 2.3:1, 2.5:1 or any value between them.

[0038] In this invention, in step S2, the molar ratio of the total content of hydroxyl groups in the macromolecular polyol and the total content of hydroxyl and amino groups in the chain extender to the molar ratio of isocyanate groups in the isocyanate is preferably (0.95-1.05):1, such as 0.95:1, 0.96:1, 0.97:1, 0.98:1, 0.99:1, 1:1, 1.01:1, 1.02:1, 1.03:1, 1.04:1, 1.05:1 or any value between them.

[0039] In this invention, the chain extender is a polyglycolic acid polyol or a composition of a polyglycolic acid polyol with a small molecule diol and / or a small molecule diamine. That is, the chain extender can be entirely composed of polyglycolic acid polyol, a portion of polyglycolic acid polyol with the remainder being a small molecule diol, a portion of polyglycolic acid polyol with the remainder being a small molecule diamine, or a portion of polyglycolic acid polyol with the remainder being a combination of a small molecule diol and a small molecule diamine. Furthermore, the molar percentage of polyglycolic acid polyol in the chain extender is preferably 20% to 100%, such as 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 100%, or any value between these values. When the molar percentage of polyglycolic acid polyol in the chain extender is controlled between 20% and 100%, the resulting polyurethane exhibits superior degradation performance.

[0040] In this invention, the polyglycolic acid polyol can be commercially available or prepared using various existing methods. In a preferred embodiment, the polyglycolic acid polyol is prepared by ring-opening polymerization of glycolide in the presence of an initiator and a catalyst. Furthermore, the polyglycolic acid polyol is preferably dehydrated by vacuum drying before reacting as a chain extender component. The vacuum drying conditions may specifically include a temperature of 60–100°C and a time of 12–48 h. The initiator is generally a small-molecule diol, specifically including at least one of ethylene glycol, propylene glycol, and butanediol. The catalyst is generally an organometallic compound, specifically including stannous octoate (Sn(Oct)₂) and / or dibutyltin dilaurate. The molar ratio of the initiator to glycolide is preferably 1:(1–20), such as 1:1, 1:3, 1:5, 1:8, 1:10, 1:12, 1:15, 1:18, 1:20, or any value between them. The preferred molar ratio of catalyst to initiator is 1:(30-80), such as 1:30, 1:35, 1:40, 1:45, 1:50, 1:55, 1:60, 1:65, 1:70, 1:75, 1:80, or any value between them. The preferred conditions for the ring-opening polymerization reaction include a temperature of 60-120°C, such as 60°C, 65°C, 70°C, 75°C, 80°C, 85°C, 90°C, 95°C, 100°C, 105°C, 110°C, 115°C, 120°C, or any value between them; and a time of 0.5-6 h, such as 0.5 h, 0.8 h, 1 h, 1.2 h, 1.5 h, 1.8 h, 2 h, 2.5 h, 3 h, 3.5 h, 4 h, 4.5 h, 5 h, 5.5 h, 6 h, or any value between them. Furthermore, the ring-opening polymerization reaction can be carried out in the presence of an organic solvent. Examples of such organic solvents include at least one selected from toluene, dioxane, N,N-dimethylformamide (DMF), and dimethyl sulfoxide (DMSO), with toluene and / or dioxane being preferred. During the ring-opening polymerization reaction, the reaction system can be protected or purged with an inert gas to ensure the isolation of water and oxygen, which are detrimental to the ring-opening reaction, and to avoid the formation of byproducts due to the presence of water or oxygen, thereby increasing the molecular weight of the reaction product and the reaction yield.

[0041] In this invention, the conditions for the nucleophilic addition reaction preferably include a temperature of 70–110°C, such as 70°C, 75°C, 80°C, 85°C, 90°C, 95°C, 100°C, 105°C, 110°C, or any value between them; and a time of 1–3 h, such as 1 h, 1.5 h, 2 h, 2.5 h, 3 h, or any value between them. Furthermore, the nucleophilic addition reaction is preferably carried out in the presence of a catalyst. The catalyst is generally an organometallic compound, specifically exemplified by stannous octoate (Sn(Oct)₂) and / or dibutyltin dilaurate.

[0042] In this invention, the chain extension reaction conditions preferably include a temperature of 70–110°C, such as 70°C, 75°C, 80°C, 85°C, 90°C, 95°C, 100°C, 105°C, 110°C or any value between them; and a time of 12–36 h, such as 12 h, 14 h, 16 h, 18 h, 20 h, 24 h, 28 h, 30 h, 32 h, 36 h or any value between them.

[0043] In this invention, the nucleophilic addition reaction and chain extension reaction can be carried out in the presence of an organic solvent. The organic solvent may include at least one of toluene, dioxane, N,N-dimethylformamide (DMF), and dimethyl sulfoxide (DMSO), preferably dimethyl sulfoxide.

[0044] In this invention, after the chain extension reaction is completed, the unreacted monomers, initiators and catalysts in the resulting reaction products can be separated from the polymer by dissolving them in non-solvents of the polymer such as water and methanol, and the polymer can be purified by dialysis, centrifugation, filtration and other methods.

[0045] Furthermore, the present invention also provides the application of the biodegradable polyurethane in the medical and packaging fields.

[0046] Specific applications of the biodegradable polyurethane provided by this invention can be listed below:

[0047] One application is that it can be made into soft tissue filling materials using microsphere technology, and it can also be made into tissue repair membranes using electrospinning technology.

[0048] Application 2: It can be processed into tissue filling materials or tissue engineering scaffold materials with different shapes through thermoplastic molding, 3D printing, melt extrusion stretching and other processing methods.

[0049] Application 3: Apply the above-mentioned spheres, membranes, molded parts, 3D printing materials, etc., to biomedical and cosmetic products, including but not limited to biodegradable coated cartilage repair scaffolds, implantable devices, implantable artificial organs, contact artificial organs, stents, interventional catheters, medical dressings, organ assist devices, etc.

[0050] Application 4: Biodegradable polyurethane composites with metal or polymer materials can be used to create structures, compositions, and shapes suitable for blood vessels, veins, esophagus, bile ducts, trachea, bronchi, small intestine, large intestine, urethra, ureter, or other segments near tubular passages. These include, but are not limited to, vascular stents, tracheal stents, bronchial stents, urethral stents, esophageal stents, biliary stents, ureteral stricture stents, stents for the small intestine, and stents for the large intestine.

[0051] Application 5: Medical devices or cosmetic products made of biodegradable polyurethane can incorporate commercially available or publicly disclosed peptides, proteins, active ingredients, and drugs into the polyurethane material according to clinical needs. These include physiologically active drugs with anti-proliferation, anti-migration, anti-angiogenesis, anti-inflammatory, anti-inflammatory, cell growth inhibition, cytotoxic, or anti-thrombotic effects, including but not limited to growth factors, carnosine, collagen peptides, heparin, insulin-like growth factor, astaxanthin, etc.

[0052] The technical solution of the present invention will be further described in detail below with reference to specific embodiments. It should be understood that the following embodiments are merely illustrative and explanatory of the present invention, and should not be construed as limiting the scope of protection of the present invention. All technologies implemented based on the above content of the present invention are covered within the scope of protection intended by the present invention.

[0053] Unless otherwise stated, the raw materials and reagents used in the following examples are commercially available products or can be prepared by known methods.

[0054] In Example 1, anhydrous toluene was dried with sodium benzoate and refluxed for 2 hours. The glycolide monomer was purified three times by recrystallization from ethyl acetate.

[0055] In the following examples and comparative examples, the hydrogen nuclear magnetic resonance (NMR) spectrum was used to measure the nuclear magnetic resonance (NMR) spectrum. 1 Characterize the chemical structure of the product using 1H NMR; 1 1H NMR spectroscopy was performed by dissolving the product in deuterated trifluoroacetic acid (D-TFA). The molecular weight of the product was characterized by gel permeation chromatography (GPC), and the GPC curve was obtained by dissolving the product in N,N-dimethylformamide (DMF). The thermal properties of the product were characterized by differential scanning calorimetry (DSC).

[0056] Preparation Example 1: Preparation of Polyglycolic Acid Polyols

[0057] The reaction flask was evacuated three times to fill it with a nitrogen atmosphere. Under nitrogen protection, 2.0 g of glycolide and 4 mL of anhydrous toluene were added to the flask. After the glycolide was completely dissolved, 248 mg of ethylene glycol initiator and 40 mg of Sn(Oct)₂ catalyst were added sequentially to the flask under N₂ protection using a pipette. The reaction flask was sealed and reacted in an oil bath at 110 °C for 1 h. After the reaction was completed, the flask was cooled and precipitated with methanol at a volume ratio of 10:1. The precipitate was dissolved in 8 mL of hexafluoroisopropanol by sonication, and then precipitated again with methanol. Finally, the product was washed three times with methanol and dried in a vacuum oven at 60 °C for 24 h to obtain polyglycolic acid polyol. The number average molecular weight of the synthesized polyglycolic acid polyol was calculated to be 500 by 1H NMR spectroscopy.

[0058] Preparation Example 2: Preparation of Polyglycolic Acid Polyols

[0059] The reaction flask was evacuated three times to fill it with a nitrogen atmosphere. Under nitrogen protection, 2.0 g of glycolide and 4 mL of anhydrous toluene were added to the flask. After the glycolide was completely dissolved, 68 mg of ethylene glycol initiator and 20 mg of Sn(Oct)₂ catalyst were added sequentially to the flask under N₂ protection using a pipette. The reaction flask was sealed and reacted in an oil bath at 110 °C for 2.5 h. After the reaction was completed, the flask was cooled and precipitated with methanol at a volume ratio of 10:1. The precipitate was dissolved in 8 mL of hexafluoroisopropanol by sonication and then precipitated again with methanol. Finally, the product was washed three times with methanol and dried in a vacuum oven at 60 °C for 24 h to obtain polyglycolic acid polyol. The number average molecular weight of the synthesized polyglycolic acid polyol was calculated to be 1800 by 1H NMR spectroscopy.

[0060] Example 1: Preparation of Biodegradable Polyurethane (PUGA)

[0061] 500 mg of polyglycolic acid polyol (number average molecular weight 500 Da) was placed in a reaction flask and dried under vacuum in an oil bath at 80 °C for 1 h. Then, 4 mL of ultra-dry DMSO was added and stirred to dissolve the polyglycolic acid polyol chain extender, yielding a chain extender solution. 2 g of polycaprolactone diol (number average molecular weight 2000 Da) was weighed and added to another reaction flask. After drying under vacuum in an oil bath at 80 °C for 30 min, the atmosphere was replaced with nitrogen. Under nitrogen purging, 8 mL of ultra-dry DMSO, 355 μL of diisocyanate (HDI), and 10 μL of Sn(Oct)₂ were added sequentially to the reaction flask. The flask was then sealed and reacted at 90 °C for 2 h. After the reaction was complete, the chain extender solution was added to a reaction flask containing polyurethane prepolymer and reacted at 90 °C for 16 h. After the reaction was complete, the reaction solution was cooled to room temperature, the product was separated and purified, and then dried under vacuum to obtain biodegradable polyurethane (PUGA). The product was identified by 1H NMR spectroscopy, and the detection results were... Figure 1 The successful synthesis of PUGA was confirmed; its number-average molecular weight was 27 kDa, as determined by GPC.

[0062] Example 2: Preparation of biodegradable polyurethane (0.8 PUGA)

[0063] 400 mg of polyglycolic acid polyol (number average molecular weight 500 Da) was placed in a reaction flask and dried under vacuum in an oil bath at 80 °C for 1 h. Then, 4 mL of ultra-dry DMSO was added and stirred to dissolve the polyglycolic acid polyol chain extender, yielding a chain extender solution. 2 g of polycaprolactone diol (number average molecular weight 2000 Da) was weighed and added to another reaction flask. After drying under vacuum in an oil bath at 80 °C for 30 min, the atmosphere was replaced with nitrogen. Under nitrogen purging, 8 mL of ultra-dry DMSO, 355 μL of diisocyanate (HDI), and 10 μL of Sn(Oct)2 were added sequentially to the reaction flask. The reaction flask was then sealed and reacted at 70 °C for 3 h. After the reaction was complete, the polyglycolic acid polyol chain extender solution was added to a reaction flask containing polyurethane prepolymer and reacted at 70 °C for 0.5 h. Then, 18 mg of 1,4-butanediol (BDO) was added to the reaction flask after shaking and mixing with 1 mL of ultra-dry DMSO, and the reaction was carried out for 16 h. After the reaction was complete, the reaction solution was cooled to room temperature, the product was separated and purified, and then vacuum dried to obtain biodegradable polyurethane (0.8 PUGA). The product was identified by 1H NMR spectroscopy, and the detection results were as follows (…). Figure 1 The successful synthesis of 0.8 PUGA was confirmed; its number-average molecular weight was 27 kDa, as determined by GPC.

[0064] Example 3: Preparation of biodegradable polyurethane (0.6PUGA)

[0065] Take 300 mg of polyglycolic acid polyol (number average molecular weight of 500 Da) in another reaction flask, dry it under vacuum in an oil bath at 80 °C for 1 h, then add 4 mL of ultra-dry DMSO and stir to dissolve the polyglycolic acid polyol chain extender to obtain a chain extender solution. Weigh 2 g of polycaprolactone diol (number average molecular weight of 2000 Da) and add it to another reaction flask. Dry it under vacuum in an oil bath at 80 °C for 30 min, then replace it with a nitrogen atmosphere. Under nitrogen purging, add 8 mL of ultra-dry DMSO, 355 μL of diisocyanate (HDI), and 10 μL of Sn(Oct)2 to the reaction flask in sequence. Then seal the reaction flask and react at 110 °C for 1 h. After the reaction is complete, add the chain extender solution to the reaction flask containing polyurethane prepolymer, and seal and react at 110 °C for 0.5 h. Then take 36 mg of BDO and mix it with 1 mL of ultra-dry DMSO by shaking, add it to the reaction flask and react for 16 h. After the reaction was complete, the reaction solution was cooled to room temperature, the product was separated and purified, and then vacuum dried to obtain biodegradable polyurethane (0.6 PUGA). The product was identified by 1H NMR spectroscopy, and the detection results were as follows (…). Figure 1 The successful synthesis of 0.6 PUGA was confirmed; its number-average molecular weight was 26 kDa, as determined by GPC.

[0066] Example 4: Preparation of biodegradable polyurethane (0.4 PUGA)

[0067] Take 200 mg of polyglycolic acid polyol (number average molecular weight of 500 Da) in another reaction flask, dry it under vacuum in an oil bath at 80 °C for 1 h, then add 4 mL of ultra-dry DMSO and stir to dissolve the polyglycolic acid polyol chain extender to obtain a chain extender solution. Weigh 2 g of polycaprolactone diol (number average molecular weight of 2000 Da) and add it to another reaction flask. Dry it under vacuum in an oil bath at 80 °C for 30 min, then replace it with a nitrogen atmosphere. Under nitrogen purging, add 8 mL of ultra-dry DMSO, 355 μL of diisocyanate (HDI), and 10 μL of Sn(Oct)2 to the reaction flask in sequence. Then seal the reaction flask and react at 90 °C for 2 h. After the reaction is complete, add the polyglycolic acid polyol chain extender solution to the reaction flask containing polyurethane prepolymer, and seal and react at 90 °C for 0.5 h. Then, take 54.1 mg of BDO and mix it with 1 mL of ultra-dry DMSO by shaking, add it to the reaction flask, and react for 16 h. After the reaction was complete, the reaction solution was cooled to room temperature, the product was separated and purified, and then vacuum dried to obtain biodegradable polyurethane (0.4 PUGA). The product was identified by 1H NMR spectroscopy, and the detection results were as follows (…). Figure 1 The successful synthesis of 0.4 PUGA was confirmed; its number-average molecular weight was 26 kDa, as determined by GPC.

[0068] Example 5: Preparation of biodegradable polyurethane (PTMG-PUGA)

[0069] Biodegradable polyurethane was prepared according to the method of Example 1, except that polycaprolactone diol (number average molecular weight 2000 Da) was replaced with the same molar amount of dihydroxy polytetrahydrofuran (number average molecular weight 2000 Da), while the other conditions were the same as in Example 1, resulting in biodegradable polyurethane (PTMG-PUGA). The product was identified by 1H NMR spectroscopy, and the results confirmed the successful synthesis of PTMG-PUGA; its number average molecular weight was 18 kDa as determined by GPC.

[0070] Example 6: Preparation of biodegradable polyurethane (PUGAˋ)

[0071] Biodegradable polyurethane was prepared according to the method of Example 1, except that the polyglycolic acid polyol (number average molecular weight of 500 Da) was replaced with the same amount of polyglycolic acid polyol (number average molecular weight of 1800 Da) in the same proportions by weight. All other conditions were the same as in Example 1, resulting in biodegradable polyurethane (PUGAˋ). The product was identified by 1H NMR spectroscopy, and the results confirmed the successful synthesis of PUGAˋ. GPC characterization showed its number average molecular weight to be 24 kDa.

[0072] Example 7: Preparation of biodegradable polyurethane (PBA-PUGA)

[0073] Biodegradable polyurethane was prepared according to the method of Example 1, except that polycaprolactone diol (number average molecular weight 2000 Da) was replaced with the same molar amount of polybutylene adipate diol (number average molecular weight 2000 Da), while the other conditions were the same as in Example 1, resulting in biodegradable polyurethane (PBA-PUGA). The product was identified by 1H NMR spectroscopy, and the results confirmed the successful synthesis of PBA-PUGA; its number average molecular weight was determined to be 27 kDa by GPC characterization.

[0074] Comparative Example 1: Preparation and Characterization of Polyurethane (PU)

[0075] 90.1 mg of BDO was added to 2 mL of ultra-dry DMSO and shaken to obtain a BDO DMSO solution. 2 g of polycaprolactone diol (number average molecular weight 2000 Da) was weighed and added to another reaction flask. After vacuum drying in an oil bath at 80 °C for 30 min, the atmosphere was replaced with nitrogen. Under nitrogen purging, 8 mL of ultra-dry DMSO, 355 μL of HDI, and 10 μL of Sn(Oct)₂ were added sequentially to the reaction flask. The flask was then sealed and reacted at 70 °C for 3 h. After the reaction was complete, the BDO DMSO solution was added to a reaction flask containing polyurethane prepolymer, sealed, and reacted in an oil bath at 80 °C for 8 h. After the reaction was complete, the reaction solution was cooled to room temperature, the product was separated and purified, and then vacuum dried to obtain polyurethane (PU). The product was identified by 1H NMR spectroscopy. The detection results were as follows (…). Figure 1 The successful synthesis of polyurethane was confirmed; its number-average molecular weight was 26 kDa, as determined by GPC.

[0076] Comparative Example 2: Preparation of Biodegradable Polyurethane (DPUGA)

[0077] Biodegradable polyurethane was prepared according to the method in Example 1, except that all raw materials were fed in one step. The specific steps are as follows:

[0078] 500 mg of polyglycolic acid polyol (number average molecular weight 500 Da) was placed in a reaction flask and dried under vacuum in an oil bath at 80 °C for 1 h. Then, 4 mL of ultra-dry DMSO was added and stirred to dissolve the polyglycolic acid polyol chain extender, yielding a chain extender solution. 2 g of polycaprolactone diol (number average molecular weight 2000 Da) was weighed and added to another reaction flask. After drying under vacuum in an oil bath at 80 °C for 30 min, the atmosphere was replaced with nitrogen. Under nitrogen purging, 8 mL of ultra-dry DMSO, 355 μL of diisocyanate (HDI), 10 μL of Sn(Oct)2, and the chain extender solution were sequentially added to the reaction flask, sealed, and reacted at 90 °C for 18 h. After the reaction was complete, the reaction solution was cooled to room temperature, the product was separated and purified, and then dried under vacuum to obtain the reference biodegradable polyurethane (DPUGA).

[0079] Comparative Example 3: Preparation of Polyurethane (PBA-PU)

[0080] Biodegradable polyurethane was prepared according to the method of Comparative Example 1, except that polycaprolactone diol (number average molecular weight 2000 Da) was replaced with the same molar amount of polybutylene adipate diol (number average molecular weight 2000 Da), while the other conditions were the same as in Comparative Example 1, resulting in biodegradable polyurethane (PBA-PU). The product was identified by 1H NMR spectroscopy, and the results confirmed the successful synthesis of PBA-PU; its number average molecular weight was determined to be 27 kDa by GPC characterization.

[0081] Test Example 1: Characterization of the tensile properties of polyurethane

[0082] The polyurethanes obtained in Examples 1-7 and Comparative Examples 1-3 were dissolved in hexafluoroisopropanol and cast into ultrapenetrating dishes with a diameter of 8 cm. After the solvent had completely evaporated, the polymer film was placed between PTFE films, and a polyurethane film with a diameter of 10 cm and a thickness of 150 micrometers was obtained using a hot press at 100°C and 0.5 MPa. The polyurethane film was formed into dumbbell-shaped strips using a stamping machine, and the tensile properties of Examples 1-7 and Comparative Examples 1-3 were characterized on a universal tensile testing machine at a tensile rate of 100 mm / min. The tensile strength and elongation at break of Examples 1-7 and Comparative Examples 1-3 are shown in Table 1. As can be seen from Table 1, after introducing the polyglycolic acid chain extender, the tensile strength of Examples 1-4 increased by 6-124% compared to Comparative Example 1, and the elongation at break increased by up to 58%; the tensile strength of Examples 1-4 increased by 35-186% compared to Comparative Example 2, and the elongation at break increased by up to 130%. This indicates that the polyglycolic acid chain extender effectively improved the mechanical properties of polyurethane. Furthermore, the tensile strength of Example 1 was increased by 74% compared to Example 5, and the elongation at break of Example 1 was increased by 26% compared to Example 5; the tensile strength of Example 7 was increased by 90% compared to Comparative Example 3, and the elongation at break of Example 7 was increased by 101% compared to Comparative Example 3. This demonstrates that when the macromolecular polyol is a flexible polyester polyol, the mechanical properties of the resulting polyurethane can be significantly improved. The tensile strength of Example 1 was increased by 44% compared to Example 6, and the elongation at break of Example 1 was increased by 32% compared to Example 6. This indicates that when the number average molecular weight of the polyglycolic acid polyol is controlled between 200 and 500 Da, the mechanical property enhancement effect is even better.

[0083] Table 1. Tensile property characterization of Examples 1-7 and Comparative Examples 1-3

[0084] sample Tensile strength (MPa) Elongation at break (%) Example 1 30.0 1508.6 Example 2 19.8 1147.3 Example 3 14.2 1023.9 Example 4 15.3 914.9 Example 5 17.2 1199.7 Example 6 20.9 1143.6 Example 7 27.8 1193.2 Comparative Example 1 13.4 855.6 Comparative Example 2 10.5 655.9 Comparative Example 3 14.6 595.1

[0085] Test Example 2: Characterization of the Degradation Properties of Polyurethane

[0086] The degradation performance of polyurethane was characterized by in vitro enzymatic hydrolysis. An enzyme solution prepared from *Pseudomonas cepacia* lipase and a phosphate buffer solution at pH 7.2–7.4 was used as the in vitro degradation medium. The polyurethanes synthesized in Examples 1–7 and Comparative Examples 1–3 were prepared into square film samples with sides of 5 mm and a thickness of 150 μm. Three parallel experiments were set up for each group. The enzyme degradation solution was changed every two days to maintain enzyme activity. After degradation for a certain period, the samples were removed, washed with deionized water, dried, weighed, and the mass loss rate was calculated. The results for Examples 1–4 and Comparative Examples 1–2 are shown below. Figure 2 The results of Examples 1, 7, Comparative Example 1, and Comparative Example 3 are shown in the figure. Figure 3 .from Figure 2 It can be seen that after introducing the polyglycolic acid chain extender, the degradation rate of Examples 1-4 within 24 days increased by 80-179% compared to Comparative Example 1; the degradation rate of Example 1 within 24 days increased by 61% compared to Comparative Example 2. Figure 3 It can be seen that the degradation rate of Example 7 within 24 days was 178% higher than that of Comparative Example 3. This indicates that the polyglycolic acid chain extender effectively improves the degradation performance of polyurethane. Furthermore, the degradation rate of Example 6 within 24 days was 30%. Calculations show that the degradation rate of Example 1 was 40% higher than that of Example 6. Therefore, it is evident that the degradation effect is better when the number average molecular weight of the polyglycolic acid polyol is controlled between 200 and 500 Da.

[0087] Test Example 3: Characterization of Degradation Products of Polyurethane

[0088] The residues after long-term in vitro enzymatic hydrolysis of Examples 1 and Comparative Example 1 were characterized by 1H NMR spectroscopy, gel permeation chromatography, and differential scanning calorimetry. The 1H NMR spectra of the residues after degradation are shown in the figure. Figure 4 GPC curves of pre-degradation products and long-term degradation residues are shown in [reference needed]. Figure 5 The DSC curves of the pre-degradation products, the residues after long-term degradation, and the polycaprolactone diol used, after one cooling and two heating cycles, are shown in the figure. Figure 6 . Figure 5 and Figure 6 In this context, PCL2k represents polycaprolactone diol with a number average molecular weight of 2000 used in the examples and comparative examples. Figure 4 , Figure 5 and Figure 6It can be seen that PUGA (Example 1) had a mass loss rate of 95% after 54 days of degradation. The molecular weight of the degradation residue was close to that of the polycaprolactone diol used. The melting point and crystallization temperature of the degradation residue were also close to those of the polycaprolactone diol used. This indicates that PUGA had been completely degraded into fragments derived from the soft segment of polycaprolactone diol. This proves that the polyglycolic acid polyol segments are located between the polycaprolactone segments and form low molecular weight residues through hydrolysis. PU (Comparative Example 1) had a mass loss rate of 50% after 112 days of degradation. The molecular weight of the degradation residue was slightly lower than that of PU before degradation. The melting point and crystallization temperature of the degradation residue were close to those of PU before degradation. This indicates that PU was only partially degraded, and the degradation residue was still polyurethane with a higher molecular weight.

[0089] Although embodiments of the present invention have been shown and described above, it is understood that the above embodiments are exemplary and should not be construed as limiting the present invention. Those skilled in the art can make changes, modifications, substitutions and variations to the above embodiments within the scope of the present invention without departing from the principles and spirit of the present invention.

Claims

1. A process for the preparation of a biodegradable polyurethane, characterized in that, The method comprises the following steps: S1. carrying out nucleophilic addition reaction between isocyanate and macromolecular polyol selected from at least one of polyester polyol, polyether polyol and polycarbonate polyol with number average molecular weight of 1kDa-8kDa, to obtain double-end isocyanate-terminated polyurethane prepolymer; S2. carrying out chain extension reaction between polyurethane prepolymer and polyglycolic acid polyol or combination of polyglycolic acid polyol, small molecule diol and / or small molecule diamine as chain extender, to obtain biodegradable polyurethane.

2. The method of producing a biodegradable polyurethane according to claim 1, characterized by, In step S1, the molar ratio of isocyanate in the isocyanate to hydroxyl in the macromolecular polyol is (1.1-2.5):

1.

3. The method of producing a biodegradable polyurethane according to claim 1, characterized by, In step S2, the molar ratio of total content of hydroxyl in the macromolecular polyol and hydroxyl and amine in the chain extender to isocyanate in the isocyanate is (0.95-1.05):1; the molar ratio of polyglycolic acid polyol in the chain extender is 20-100%.

4. The method of producing a biodegradable polyurethane according to claim 1, characterized by, The conditions of the nucleophilic addition reaction include temperature of 70-110℃ and time of 1-3h.

5. The method of producing a biodegradable polyurethane according to claim 1, characterized by, The conditions of the chain extension reaction include temperature of 70-110℃ and time of 12-36h.

6. The method of producing a biodegradable polyurethane according to claim 1, characterized by, The isocyanate is selected from at least one of hexamethylene diisocyanate, lysine diisocyanate, toluene diisocyanate, diphenylmethane diisocyanate, isophorone diisocyanate and 4,4'-dicyclohexylmethane diisocyanate; the small molecule diol is selected from at least one of ethylene glycol, propylene glycol and butylene glycol; and the small molecule diamine is selected from at least one of ethylenediamine, propylenediamine and butylenediamine.

7. The method of producing a biodegradable polyurethane according to claim 1, characterized by, The biodegradable polyurethane has number average molecular weight of 10kDa-100kDa.

8. Biodegradable polyurethane prepared by the method of any one of claims 1-7.

9. Application of the biodegradable polyurethane of claim 8 in medical and packaging fields.

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