Degradable polyurethane as well as preparation method and application thereof

Abstract

The invention belongs to the technical field of polyurethane, and relates to a polyurethane material as well as a preparation method and application thereof. The biodegradable polyurethane has a structure as shown in a formula (1). The polyurethane provided by the invention has controllable degradation performance and excellent mechanical properties, so that the use requirements of different application scenes are met. # imgabs0 #

Description

Technical Field

[0001] The invention belongs to the technical field of polyurethane and relates to a polyurethane material and a preparation method and application thereof. Background Art

[0002] With the rapid development of the plastics industry, plastics are increasingly used in different industries and fields. At the same time, the degradability of plastics has also received more and more attention. Degradable plastic products can reduce the degree of environmental pollution and promote the sustainable development of the environment. Thermoplastic polyurethane elastomer (TPU) has been widely used in many fields due to its high strength, high wear resistance, wide hardness range, and wide processing temperature. At present, the annual consumption of polyurethane elastomers can reach 20 million tons, but polyurethane elastomers are not easy to degrade in nature and are difficult to recycle. At the end of their service life, they are often incinerated or landfilled, which poses environmental pollution problems. Therefore, adhering to the concept of green and environmentally friendly development, the biodegradability of polyurethane elastomers and the bio-based source of raw materials have received extensive attention from academia and industry.

[0003] Typical linear TPU is a multi-block thermoplastic elastomer generated by the reaction of polymer diol, diisocyanate and small molecule diol or diamine. According to the mobility of the chain segment, the microphase generated by the polymer diol is generally called the soft segment, which gives the polyurethane elasticity; the microphase generated by the isocyanate and small molecule diol or diamine is called the hard segment, which provides mechanical strength for the polyurethane.

[0004] At present, for the development of biodegradability of TPU, related research mainly adopts replacing the soft segment components with biodegradable polymer polyols, such as vegetable oil-based polyols, polyester polyols, etc. CN116355174A uses polycarbonate degradable polyols as soft segments, but the main chain contains a benzene ring structure, which causes the material to have potential biological toxicity and a long degradation cycle. CN113968954A introduces polylactic acid / polybutylene terephthalate-adipate / polyester polyol blocks into the polyester polyol system to make the soft segment of TPU degrade quickly, but the elongation at break of the product obtained in this way is generally low, which is limited in some application fields. CN117510774A synthesizes polyurethane based on PGA diol and PPC diol, but the degradation rate of the final synthetic product is uncontrollable. In summary, the degradation rate of soft-segment degradable TPU can be controlled in a very limited range, and it is still difficult to meet the needs of practical application scenarios such as drug release, plastic surgery, and tissue engineering. In particular, it is difficult to achieve the goal of flexibly controlling the degradation rate of the material over a large range to match the growth rates of different tissues.

[0005] The improvement of the hard segment degradation rate is mainly achieved by selecting a small molecule chain extender or a degradable diisocyanate containing an easily degradable group. CN113195197A designs a chain extender with a degradable group for polyurethanes with a high hard segment content (30-60%), but does not clearly regulate the degradation rate. CN113603852A synthesizes undecylenic acid diol and undecylenic acid diol chain extenders containing different hanging chain lengths. The polyurethane prepared by reacting the chain extender with polyol as a raw material contains hanging chains, which reduces the crystallinity of the polyurethane and thus improves the degradation efficiency, but the mechanical strength of the corresponding polyurethane material is low. CN108059706A selects lysine diisocyanate to synthesize polycaprolactone-based polyurethane, but while giving the hard segment degradability, it often causes damage to mechanical properties, thermal stability, biocompatibility, etc. Therefore, how to achieve a balance between the degradation performance of polyurethane materials and other properties such as mechanical properties, and give polyurethane good mechanical properties and flexibly regulated degradation performance, is still a problem that needs to be urgently solved. Summary of the invention

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

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

[0008]

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

[0010] In a second aspect, the method for preparing biodegradable polyurethane provided by the present invention comprises the following steps:

[0011] S1. subjecting an isocyanate and a macromolecular polyol to a nucleophilic addition reaction, wherein the macromolecular polyol is selected from at least one of a polyester polyol, a polyether polyol and a polycarbonate polyol having a number average molecular weight of 1 kDa to 8 kDa, to obtain a double-ended isocyanate-terminated polyurethane prepolymer;

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

[0013] In a third aspect, the present invention provides applications of the above-mentioned biodegradable polyurethane in the fields of medicine and packaging.

[0014] The key of the present invention is to select a macromolecular polyol with a specific molecular weight as the soft segment of the polyurethane, and adopt a two-step method (prepolymer method) to first end-cap the macromolecular polyol with isocyanate, and then use a chain extender containing polyglycolic acid polyol to carry out a chain extension reaction, so that the chemical composition and structure of the polyurethane can be changed, so that the obtained polyurethane structure is orderly and has higher regularity, and the degradable segment is located at the hard segment position of the polyurethane and is evenly distributed in the hard segment, and the soft segment and the hard segment are precisely arranged in segments, so that the polyurethane is customized and designed, and its degradation rate can be effectively regulated, thereby giving the polyurethane controllable degradation performance and excellent mechanical properties to meet the use requirements of different application scenarios. In addition, the characteristics of the biodegradable polyurethane provided by the present invention are particularly beneficial for the development of materials that can be partially degraded, completely degraded or nearly completely degraded within a specific time range, and are particularly suitable for scenes where degradation treatment is required after the polyurethane material fails. BRIEF DESCRIPTION OF THE DRAWINGS

[0015] Figure 1 The hydrogen nuclear magnetic resonance spectra of the degradable polyurethanes synthesized in Examples 1 to 4 and the polyurethane synthesized in Comparative Example 1;

[0016] Figure 2 Degradation curves of the degradable polyurethanes synthesized in Examples 1 to 4 and the polyurethanes synthesized in Comparative Examples 1 to 2;

[0017] Figure 3 Degradation curves of the degradable polyurethanes synthesized in Example 1 and Example 7 and the polyurethanes synthesized in Comparative Example 1 and Comparative Example 3;

[0018] Figure 4 The hydrogen nuclear magnetic resonance spectra of the residues after long-term degradation of the degradable polyurethane synthesized in Example 1 and the polyurethane synthesized in Comparative Example 1;

[0019] Figure 5 The GPC curves of the degradable polyurethane synthesized in Example 1 and the polyurethane synthesized in Comparative Example 1 before degradation and the residue after long-term degradation;

[0020] Figure 6 The DSC curves of the first cooling and second heating of the degradable polyurethane synthesized in Example 1 and the polyurethane synthesized in Comparative Example 1 before degradation and the residue after long-term degradation, as well as the polycaprolactone diol used. DETAILED DESCRIPTION

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

[0022]

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

[0024] In the present invention, R1 is derived from isocyanate, that is, a residue formed at the isocyanate end after a nucleophilic addition reaction between an isocyanate and a macromolecular polyol. The type of the isocyanate is not particularly limited, and may be any of various existing compounds having an isocyanate functionality of 2 or more, and specific examples thereof include, but are 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 the present invention, R2 is derived from polyglycolic acid polyol or a combination of polyglycolic acid polyol and small molecule diol and / or small molecule diamine, that is, a residue formed at the end of the chain extender after the chain extender (polyglycolic acid polyol or a combination of polyglycolic acid polyol and small molecule diol and / or small molecule diamine) reacts with isocyanate. That is, R2 may be entirely derived from polyglycolic acid polyol, partially derived from polyglycolic acid polyol and the remainder from small molecule diol, partially derived from polyglycolic acid polyol and the remainder from small molecule diamine, or partially derived from polyglycolic acid polyol and the remainder from a combination of small molecule diol and small molecule diamine. In addition, the molar proportion of polyglycolic acid polyol 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 therebetween. The molar proportion here refers to the ratio of the molar amount of polyglycolic acid polyol in R2 to the total molar amount of polyglycolic acid polyol and small molecule diol and small molecule diamine. When the proportion of polyglycolic acid polyol in R2 is controlled at 20-100%, the degradation performance of the obtained polyurethane is better.

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

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

[0028] In the present invention, the type of the small molecule diamine is not particularly limited, and is preferably a C2-C5 diamine, specifically at least one of ethylenediamine, propylenediamine and butylenediamine.

[0029] In the present invention, R3 is derived from a macromolecular polyol, that is, a residue formed at the end of the macromolecular polyol after a nucleophilic addition reaction between the macromolecular polyol and isocyanate. The macromolecular polyol is selected from at least one of polyester polyols, polyether polyols and polycarbonate polyols. Compared to polyurethanes in which R3 is derived from other polyols, when R3 is derived from a flexible polyester polyol such as polycaprolactone polyol and polybutylene adipate polyol, the mechanical properties of the resulting polyurethane can be significantly improved. 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 therebetween.

[0030] In the present invention, n≥1, and specifically can 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. In addition, 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 therebetween.

[0031] The biodegradable polyurethane provided by the present invention can be degraded 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 degradation at 20-45°C for 12 months is generally more than 20%, for example, it can be 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100% or any value therebetween.

[0032] The biodegradable polyurethane obtained by using a component containing polyglycolic acid polyol as a chain extender provided by the present invention has higher ultimate tensile strength than the polyurethane obtained by using a component not containing polyglycolic acid polyol as a chain extender, and 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 preparation method of the biodegradable polyurethane provided by the present invention comprises the following steps:

[0034] S1. subjecting isocyanate and macromolecular polyol to a nucleophilic addition reaction to obtain a diisocyanate-terminated polyurethane prepolymer;

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

[0036] In the present invention, the macromolecular polyol is selected from at least one of polyester polyol, polyether polyol and polycarbonate polyol, wherein 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 therebetween.

[0037] In the present invention, in step S1, the molar ratio of isocyanate in the isocyanate to hydroxyl in the macromolecular polyol is preferably (1.1-2.5):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 therebetween.

[0038] In the present invention, in step S2, the molar ratio of the total content of hydroxyl groups in the macromolecular polyol and hydroxyl groups and amine groups in the chain extender to the isocyanate 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 therebetween.

[0039] In the present invention, the chain extender is a polyglycolic acid polyol or a composition of a polyglycolic acid polyol and a small molecule diol and / or a small molecule diamine. That is, the chain extender can be all polyglycolic acid polyol, a part of it can be polyglycolic acid polyol and the rest can be a small molecule diol, a part of it can be polyglycolic acid polyol and the rest can be a small molecule diamine, or a part of it can be polyglycolic acid polyol and the rest can be a composition of a small molecule diol and a small molecule diamine. In addition, the molar proportion 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 therebetween. When the molar proportion of polyglycolic acid polyol in the chain extender is controlled at 20 to 100%, the resulting polyurethane has better degradation performance.

[0040] In the present invention, the polyglycolic acid polyol can be obtained commercially or prepared according to various existing methods. In a preferred embodiment, the polyglycolic acid polyol is prepared according to the following method: glycolide is subjected to a ring-opening polymerization reaction in the presence of an initiator and a catalyst. In addition, before the polyglycolic acid polyol is reacted as a chain extender component, it is preferably dehydrated by vacuum drying. The vacuum drying conditions can specifically include a temperature of 60 to 100° C. and a time of 12 to 48 hours. The initiator is generally a small molecule diol, and specifically at least one of ethylene glycol, propylene glycol and butanediol can be listed. The catalyst is generally a metal organic compound, and specifically stannous octoate (Sn(Oct)2) and / or dibutyltin dilaurate can be listed. The molar ratio of the initiator to glycolide is preferably 1: (1 to 20), such as 1: 1, 1: 3, 1: 5, 1: 8, 1: 10, 1: 12, 1: 15, 1: 18, 1: 20 or any value therebetween. The molar ratio of the catalyst to the initiator is preferably 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 therebetween. The conditions for the ring-opening polymerization reaction preferably 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 therebetween; and a time of 0.5-6h, such as 0.5h, 0.8h, 1h, 1.2h, 1.5h, 1.8h, 2h, 2.5h, 3h, 3.5h, 4h, 4.5h, 5h, 5.5h, 6h or any value therebetween. In addition, the ring-opening polymerization reaction can be carried out in the presence of an organic solvent. The organic solvent can be at least one of toluene, dioxane, N,N-dimethylformamide (DMF), dimethyl sulfoxide (DMSO), etc., preferably toluene and / or dioxane. During the ring-opening polymerization reaction, the reaction system can be protected or purged with an inert gas to ensure isolation of water and oxygen that are unfavorable to the ring-opening reaction, to avoid the generation of by-products due to the presence of water or oxygen, thereby increasing the molecular weight of the reaction product and the reaction yield.

[0041] In the present invention, the conditions of the nucleophilic addition reaction preferably include a temperature of 70 to 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 therebetween; a time of 1 to 3h, such as 1h, 1.5h, 2h, 2.5h, 3h or any value therebetween. Furthermore, the nucleophilic addition reaction is preferably carried out in the presence of a catalyst. The catalyst is generally a metal organic compound, specifically exemplified by stannous octoate (Sn(Oct)2) and / or dibutyltin dilaurate.

[0042] In the present invention, the conditions of the chain extension reaction preferably include a temperature of 70 to 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 therebetween; and a time of 12 to 36h, such as 12h, 14h, 16h, 18h, 20h, 24h, 28h, 30h, 32h, 36h or any value therebetween.

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

[0044] In the present invention, after the chain extension reaction is completed, the unreacted monomers, initiators and catalysts in the obtained reaction products can be separated from the polymer by dissolving them in a non-solvent for the polymer such as water, methanol, etc., and the polymer can be purified by dialysis, centrifugation, filtration, etc.

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

[0046] The specific application modes of the biodegradable polyurethane provided by the present invention can be listed as follows:

[0047] Application 1: Soft tissue filling materials can be made through microsphere technology, and tissue repair membrane materials can also be made through electrospinning technology.

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

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

[0050] Application 4: A composite of degradable polyurethane and metal material or polymer material, made into a structure, composition and shape suitable for blood vessels, veins, esophagus, bile duct, trachea, bronchi, small intestine, large intestine, urethra, ureter or other fragments close to tubular channels, specifically including but not limited to vascular stents, tracheal stents, bronchial stents, urethral stents, esophageal stents, bile duct stents, ureteral stricture stents, stents for small intestine, and stents for large intestine.

[0051] Application 5: Medical devices or beauty products made of degradable polyurethane can add commercially available or publicly available peptides, proteins, active ingredients and drugs to polyurethane materials according to clinical needs, including anti-proliferation, anti-migration, anti-angiogenesis, anti-inflammatory, anti-inflammatory, cell growth inhibition, cytotoxicity or anti-thrombotic physiologically active drugs, including but not limited to growth factors, carnosine, collagen peptides, heparin, insulin-like growth factor, astaxanthin, etc.

[0052] The technical scheme of the present invention will be further described in detail below in conjunction with specific embodiments. It should be understood that the following embodiments are only exemplary descriptions and explanations 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 included in the scope that the present invention is intended to protect.

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

[0054] In Example 1, anhydrous toluene was dried with sodium / benzophenone and heated under reflux for 2 hours to obtain the obtained product. Glycolide monomer was purified by recrystallization of ethyl acetate three times.

[0055] In the following examples and comparative examples, by nuclear magnetic resonance hydrogen spectrum ( 1 H NMR) to characterize the chemical structure of the product; 1 The H NMR spectrum was determined 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 determined 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 polyol

[0057] The reaction bottle was evacuated three times to fill it with nitrogen atmosphere, and 2.0g glycolide and 4mL anhydrous toluene were added to the reaction bottle under nitrogen protection. After the glycolide was completely dissolved, 248mg initiator ethylene glycol and 40mg catalyst Sn(Oct)2 were added to the reaction bottle in sequence under N2 protection using a pipette. The reaction bottle was sealed and reacted in an oil bath at 110°C for 1h. After the reaction was completed, the reaction bottle was cooled and precipitated with methanol. The volume ratio of methanol to the reaction solution was 10:1. 8mL hexafluoroisopropanol was added to the precipitated product and ultrasonically dissolved and then precipitated with methanol. Finally, the product was washed with methanol 3 times and dried in a 60°C vacuum oven for 24h to obtain polyglycolic acid polyol. The number average molecular weight of the synthesized polyglycolic acid polyol was 500 calculated by hydrogen nuclear magnetic resonance spectrum.

[0058] Preparation Example 2: Preparation of polyglycolic acid polyol

[0059] The reaction bottle was evacuated three times to fill it with nitrogen atmosphere, and 2.0g glycolide and 4mL anhydrous toluene were added to the reaction bottle under nitrogen protection. After the glycolide was completely dissolved, 68mg initiator ethylene glycol and 20mg catalyst Sn(Oct)2 were added to the reaction bottle in sequence under N2 protection using a pipette. The reaction bottle was sealed and reacted in an oil bath at 110°C for 2.5h. After the reaction was completed, the reaction bottle was cooled and precipitated with methanol. The volume ratio of methanol to the reaction solution was 10:1. 8mL hexafluoroisopropanol was added to the precipitated product and ultrasonically dissolved and then precipitated with methanol. Finally, the product was washed with methanol 3 times and dried in a 60°C vacuum oven for 24h to obtain polyglycolic acid polyol. The number average molecular weight of the synthesized polyglycolic acid polyol was 1800 calculated by hydrogen nuclear magnetic resonance spectrum.

[0060] Example 1: Preparation of biodegradable polyurethane (PUGA)

[0061] Take 500mg of polyglycolic acid polyol (number average molecular weight of 500Da) in a reaction bottle, vacuum dry it in an oil bath at 80℃ for 1h, then add 4mL of ultra-dry DMSO and stir to dissolve the polyglycolic acid polyol chain extender to obtain a chain extender solution. Weigh 2g of polycaprolactone diol (number average molecular weight of 2000Da) and add it to another reaction bottle. After vacuum drying in an oil bath at 80℃ for 30min, replace it with a nitrogen atmosphere. Under nitrogen purge, take 8mL of ultra-dry DMSO, 355μL of diisocyanate (HDI), and 10μL of Sn(Oct)2 and add them to the reaction bottle in sequence. Then seal the reaction bottle and react at 90℃ for 2h. After the reaction is completed, add the chain extender solution to the reaction bottle containing the polyurethane prepolymer and seal it at 90℃ for 16h. After the reaction is completed, the reaction liquid is cooled to room temperature, the product is separated and purified, and vacuum dried to obtain biodegradable polyurethane (PUGA). The product was identified by hydrogen nuclear magnetic resonance spectrum, and the test results ( Figure 1 ) can confirm that PUGA was successfully synthesized; its number average molecular weight was 27 kDa as characterized by GPC.

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

[0063] 400 mg of polyglycolic acid polyol (number average molecular weight of 500 Da) was placed in a reaction bottle, vacuum dried in an oil bath at 80 ° C for 1 h, and then 4 mL of ultra-dry DMSO was added to dissolve the polyglycolic acid polyol chain extender to obtain a chain extender solution. 2 g of polycaprolactone diol (number average molecular weight of 2000 Da) was weighed and added to another reaction bottle, vacuum dried in an oil bath at 80 ° C for 30 min, and then replaced with a nitrogen atmosphere. Under nitrogen purge, 8 mL of ultra-dry DMSO, 355 μL of diisocyanate (HDI), and 10 μL of Sn (Oct) 2 were added to the reaction bottle in sequence, and then the reaction bottle was sealed and reacted at 70 ° C for 3 h. After the reaction was completed, the polyglycolic acid polyol chain extender solution was added to the reaction bottle containing the polyurethane prepolymer, and sealed at 70 ° C for 0.5 h, and then 18 mg of 1,4-butanediol (BDO) was taken and mixed with 1 mL of ultra-dry DMSO and added to the reaction bottle for 16 h. After the reaction is completed, the reaction solution is cooled to room temperature, the product is separated and purified, and vacuum dried to obtain biodegradable polyurethane (0.8PUGA). The product is identified by nuclear magnetic resonance hydrogen spectrum, and the test results ( Figure 1 ) can confirm that 0.8PUGA was successfully synthesized; its number average molecular weight was 27kDa as characterized by GPC.

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

[0065] 300 mg of polyglycolic acid polyol (number average molecular weight of 500 Da) was placed in another reaction bottle, vacuum dried in an oil bath at 80 ° C for 1 hour, and then 4 mL of ultra-dry DMSO was added to dissolve the polyglycolic acid polyol chain extender to obtain a chain extender solution. 2 g of polycaprolactone diol (number average molecular weight of 2000 Da) was weighed and added to another reaction bottle, vacuum dried in an oil bath at 80 ° C for 30 minutes, and then replaced with a nitrogen atmosphere. Under nitrogen purge, 8 mL of ultra-dry DMSO, 355 μL of diisocyanate (HDI), and 10 μL of Sn (Oct) 2 were added to the reaction bottle in sequence, and then the reaction bottle was sealed and reacted at 110 ° C for 1 hour. After the reaction was completed, the chain extender solution was added to the reaction bottle containing the polyurethane prepolymer, and the reaction was sealed at 110 ° C for 0.5 hours. Another 36 mg of BDO was taken and mixed with 1 mL of ultra-dry DMSO and added to the reaction bottle for 16 hours. After the reaction is completed, the reaction solution is cooled to room temperature, the product is separated and purified, and vacuum dried to obtain biodegradable polyurethane (0.6PUGA). The product is identified by nuclear magnetic resonance hydrogen spectrum, and the test results ( Figure 1 ) can confirm that 0.6PUGA was successfully synthesized; its number average molecular weight was 26kDa as characterized by GPC.

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

[0067] 200 mg of polyglycolic acid polyol (number average molecular weight of 500 Da) was placed in another reaction bottle, vacuum dried in an oil bath at 80 ° C for 1 hour, and then 4 mL of ultra-dry DMSO was added to dissolve the polyglycolic acid polyol chain extender to obtain a chain extender solution. 2 g of polycaprolactone diol (number average molecular weight of 2000 Da) was weighed and added to another reaction bottle, vacuum dried in an oil bath at 80 ° C for 30 minutes, and then replaced with a nitrogen atmosphere. Under nitrogen purge, 8 mL of ultra-dry DMSO, 355 μL of diisocyanate (HDI), and 10 μL of Sn (Oct) 2 were added to the reaction bottle in sequence, and then the reaction bottle was sealed and reacted at 90 ° C for 2 hours. After the reaction was completed, the polyglycolic acid polyol chain extender solution was added to the reaction bottle containing the polyurethane prepolymer, and the reaction was sealed at 90 ° C for 0.5 hours. Another 54.1 mg of BDO was taken and mixed with 1 mL of ultra-dry DMSO and added to the reaction bottle for 16 hours. After the reaction is completed, the reaction solution is cooled to room temperature, the product is separated and purified, and vacuum dried to obtain biodegradable polyurethane (0.4PUGA). The product is identified by nuclear magnetic resonance hydrogen spectrum, and the test results ( Figure 1 ) can confirm that 0.4PUGA was successfully synthesized; its number average molecular weight was 26kDa as characterized 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 of 2000Da) was replaced by the same molar amount of dihydroxy polytetrahydrofuran (number average molecular weight of 2000Da), and the other conditions were the same as those of Example 1 to obtain biodegradable polyurethane (PTMG-PUGA). The product was identified by hydrogen nuclear magnetic resonance spectrum, and the test results confirmed that PTMG-PUGA was successfully synthesized; GPC characterized its number average molecular weight as 18kDa.

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

[0071] Biodegradable polyurethane was prepared according to the method of Example 1, except that the polyglycolic acid polyol (number average molecular weight of 500Da) was replaced by the same weight of polyglycolic acid polyol (number average molecular weight of 1800Da), and the other conditions were the same as those of Example 1 to obtain biodegradable polyurethane (PUGAˋ). The product was identified by hydrogen nuclear magnetic resonance spectroscopy, and the test results confirmed that PUGAˋ was successfully synthesized; GPC characterized its number average molecular weight as 24kDa.

[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 of 2000Da) was replaced by polybutylene adipate diol (number average molecular weight of 2000Da) in the same molar amount, and the other conditions were the same as those of Example 1 to obtain biodegradable polyurethane (PBA-PUGA). The product was identified by hydrogen nuclear magnetic resonance spectroscopy, and the test results confirmed that PBA-PUGA was successfully synthesized; GPC characterized its number average molecular weight as 27kDa.

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

[0075] Take 90.1 mg of BDO and add 2 mL of ultra-dry DMSO to shake and mix to obtain a DMSO solution of BDO. Weigh 2 g of polycaprolactone diol (number average molecular weight is 2000 Da) and add it to another reaction bottle, and replace it with a nitrogen atmosphere after vacuum drying in an 80°C oil bath for 30 minutes. Under nitrogen purge, take 8 mL of ultra-dry DMSO, 355 μL of HDI, and 10 μL of Sn(Oct)2 and add them to the reaction bottle in sequence. Then seal the reaction bottle and react at 70°C for 3 hours. After the reaction is completed, add the DMSO solution of BDO to the reaction bottle containing the polyurethane prepolymer, seal it and react in an 80°C oil bath for 8 hours. After the reaction is completed, wait for the reaction liquid to cool to room temperature, separate and purify the product, and vacuum dry it to obtain polyurethane (PU). The product was identified by hydrogen nuclear magnetic resonance spectroscopy, and the test results ( Figure 1 ) can confirm that the polyurethane was successfully synthesized; its number average molecular weight was 26 kDa as characterized by GPC.

[0076] Comparative Example 2: Preparation of biodegradable polyurethane (DPUGA)

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

[0078] Take 500mg of polyglycolic acid polyol (number average molecular weight of 500Da) in a reaction bottle, vacuum dry it in an oil bath at 80℃ for 1h, add 4mL of ultra-dry DMSO and stir to dissolve the polyglycolic acid polyol chain extender to obtain a chain extender solution. Weigh 2g of polycaprolactone diol (number average molecular weight of 2000Da) and add it to another reaction bottle, vacuum dry it in an oil bath at 80℃ for 30min, then replace it with a nitrogen atmosphere. Under nitrogen purge, take 8mL of ultra-dry DMSO, 355μL of diisocyanate (HDI), 10μL of Sn(Oct)2 and the chain extender solution and add them to the reaction bottle in sequence, seal it and react at 90℃ for 18h. After the reaction is completed, wait for the reaction solution to cool to room temperature, separate and purify the product, and vacuum dry it to obtain a 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 of 2000Da) was replaced by polybutylene adipate diol (number average molecular weight of 2000Da) in the same molar amount, and the other conditions were the same as those of Comparative Example 1 to obtain biodegradable polyurethane (PBA-PU). The product was identified by hydrogen nuclear magnetic resonance spectrum, and the test results confirmed that PBA-PU was successfully synthesized; GPC characterized its number average molecular weight as 27kDa.

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

[0082] The polyurethane obtained in Examples 1 to 7 and Comparative Examples 1 to 3 was dissolved in hexafluoroisopropanol and cast into an ultra-flat dish with a diameter of 8 cm. After the solvent was 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 microns was obtained by using a hot press at 100°C and 0.5 MPa. The polyurethane film was made into dumbbell-shaped strips by a punching machine, and the tensile properties of Examples 1 to 7 and Comparative Examples 1 to 3 were characterized at a tensile rate of 100 mm / min on a universal tensile testing machine. The tensile strength and elongation at break of Examples 1 to 7 and Comparative Examples 1 to 3 are shown in Table 1. It can be seen from Table 1 that after the introduction of the polyglycolic acid chain extender, the tensile strength of Examples 1 to 4 was increased by 6 to 124% relative to Comparative Example 1, and the elongation at break could be increased by up to 58%; the tensile strength of Examples 1 to 4 was increased by 35 to 186% relative to Comparative Example 2, and the elongation at break could be increased by up to 130%. This shows that the polyglycolic acid chain extender effectively improves the mechanical properties of polyurethane. In addition, the tensile strength of Example 1 is increased by 74% relative to that of Example 5, and the elongation at break of Example 1 is increased by 26% relative to that of Example 5; the tensile strength of Example 7 is increased by 90% relative to that of Comparative Example 3, and the elongation at break of Example 7 is increased by 101% relative to that of Comparative Example 3. It can be seen that when the macromolecular polyol is a flexible polyester polyol, the mechanical properties of the obtained polyurethane can be significantly improved. The tensile strength of Example 1 is increased by 44% relative to that of Example 6, and the elongation at break of Example 1 is increased by 32% relative to that of Example 6. It can be seen that when the number average molecular weight of the polyglycolic acid polyol is controlled at 200 to 500 Da, the mechanical property enhancement effect is better.

[0083] Table 1 Characterization of tensile properties of Examples 1 to 7 and Comparative Examples 1 to 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 performance of polyurethane

[0086] The degradation performance of polyurethane was characterized by in vitro enzyme-catalyzed hydrolysis test. The enzyme solution prepared by Pseudomonas cepacia lipase and phosphate buffer solution with pH=7.2-7.4 was used as the medium for in vitro degradation. The polyurethanes synthesized in Examples 1-7 and Comparative Examples 1-3 were made into square film samples with a side length of 5 mm and a thickness of 150 microns. Three parallel experiments were set up for each group. The enzyme degradation solution was replaced every 2 days to maintain the activity of the enzyme. After a certain period of degradation, the samples were taken out, washed with deionized water, dried, weighed, and the mass loss rate was calculated. The results of Examples 1-4 and Comparative Examples 1-2 are shown in Table 1. Figure 2 The results of Example 1, Example 7, Comparative Example 1 and Comparative Example 3 are shown in Figure 3 .from Figure 2 It can be seen that after the introduction of the polyglycolic acid chain extender, the degradation rate of Examples 1 to 4 within 24 days increased by 80 to 179% relative to that of Comparative Example 1; the degradation rate of Example 1 within 24 days increased by 61% relative to that of Comparative Example 2. Figure 3 It can be seen that the degradation rate of Example 7 within 24 days is increased by 178% relative to that of Comparative Example 3. This indicates that the polyglycolic acid chain extender effectively improves the degradation performance of polyurethane. In addition, the degradation rate of Example 6 within 24 days is 30%. After calculation, the degradation rate of Example 1 is increased by 40% relative to that of Example 6. It can be seen that when the number average molecular weight of the polyglycolic acid polyol is controlled at 200-500 Da, the degradation effect is better.

[0087] Test Example 3: Characterization of polyurethane degradation products

[0088] The residues after long-term in vitro enzymatic hydrolysis of Example 1 and Comparative Example 1 were characterized by H NMR spectrum, gel permeation chromatography and differential scanning calorimetry. The H NMR spectrum of the residues after degradation is shown in Figure 4 The GPC curves of the products before degradation and the residues after long-term degradation are shown in Figure 5 The DSC curves of the products before degradation and the residues after long-term degradation as well as the first cooling and second heating of the polycaprolactone diol used are shown in Figure 6 . Figure 5 and Figure 6 PCL2k in the above example represents a polycaprolactone diol having 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 the mass loss rate of PUGA (Example 1) after 54 days of degradation has reached 95%, the molecular weight of the degradation residue is close to the molecular weight of the polycaprolactone diol used, and the melting point and crystallization temperature of the degradation residue are close to the melting point and crystallization temperature of the polycaprolactone diol used, indicating that PUGA has been completely degraded into fragments derived from the soft segment polycaprolactone diol, proving that the polyglycolic acid polyol segment is located between the polycaprolactone segments and forms low molecular weight residues by hydrolysis and cleavage; the mass loss rate of PU (Comparative Example 1) after 112 days of degradation reaches 50%, the molecular weight of the degradation residue is slightly lower than the molecular weight of PU before degradation, the melting point and crystallization temperature of the degradation residue are close to the melting point and crystallization temperature before degradation, indicating that PU is only partially degraded and the degradation residue is still a polyurethane with a higher molecular weight.

[0089] Although the embodiments of the present invention have been shown and described above, it is to be understood that the above embodiments are exemplary and are not to be construed as limitations on the present invention. A person skilled in the art may change, modify, replace and modify the above embodiments within the scope of the present invention without departing from the principles and intent of the present invention.

Claims

1. A biodegradable polyurethane, characterized in that: The biodegradable polyurethane has a structure shown in formula (1): R1 is derived from isocyanate; R2 is derived from polyglycolic acid polyol or a combination of polyglycolic acid polyol and small molecule diol and / or small molecule diamine, and the number average molecular weight of the polyglycolic acid polyol is less than 3000Da; R3 is derived from a macromolecular polyol, and the macromolecular polyol is selected from at least one of polyester polyols, polyether polyols and polycarbonate polyols with a number average molecular weight of 1kDa to 8kDa; n≥1.

2. The biodegradable polyurethane according to claim 1, characterized in that 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 butanediol; the small molecule diamine is selected from at least one of ethylenediamine, propylenediamine and butanediamine.

3. The biodegradable polyurethane according to claim 1, characterized in that: The molar proportion of R2 derived from polyglycolic acid polyol is 20 to 100%.

4. The biodegradable polyurethane according to claim 1, characterized in that The number average molecular weight of the biodegradable polyurethane is 10 kDa to 100 kDa.

5. The method for preparing the biodegradable polyurethane according to any one of claims 1 to 4, characterized in that: The method comprises the following steps: S1. subjecting an isocyanate and a macromolecular polyol to a nucleophilic addition reaction, wherein the macromolecular polyol is selected from at least one of a polyester polyol, a polyether polyol and a polycarbonate polyol having a number average molecular weight of 1 kDa to 8 kDa, to obtain a double-ended isocyanate-terminated polyurethane prepolymer; S2. The polyurethane prepolymer is subjected to a chain extension reaction using polyglycolic acid polyol or a combination of polyglycolic acid polyol and a small molecule diol and / or a small molecule diamine as a chain extender to obtain a biodegradable polyurethane.

6. The method for preparing biodegradable polyurethane according to claim 5, characterized in that: In step S1, the molar ratio of isocyanate in the isocyanate to hydroxyl in the macromolecular polyol is (1.1-2.5):

1.

7. The method for preparing biodegradable polyurethane according to claim 5, characterized in that: In step S2, the molar ratio of the total content of hydroxyl groups in the macromolecular polyol and hydroxyl groups and amine groups in the chain extender to isocyanate in isocyanate is (0.95-1.05):1; the molar proportion of polyglycolic acid polyol in the chain extender is 20-100%.

8. The method for preparing biodegradable polyurethane according to claim 5, characterized in that: The conditions of the nucleophilic addition reaction include a temperature of 70 to 110° C. and a time of 1 to 3 hours.

9. The method for preparing biodegradable polyurethane according to claim 5, characterized in that: The conditions of the chain extension reaction include a temperature of 70 to 110° C. and a time of 12 to 36 hours.

10. Use of the biodegradable polyurethane according to any one of claims 1 to 4 in the fields of medicine and packaging.

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