A degradable polyurethane elastomer with shape recovery at body temperature and a method of making the same

Abstract

The application discloses a preparation method of a degradable polyurethane elastomer with shape recovery at body temperature. In the application, polyglyceryl sebacate (PGS) and polyglycol sebacate prepolymers are used as soft segments of polyurethane, and isocyanate cross-linking reaction is used to obtain a shape memory polyurethane material. The polyglycol sebacate used in the application has strong crystallinity, and the polyglyceryl sebacate has relatively poor crystallinity. By properly adjusting the proportion of the two, the original shape can be recovered at body temperature. The mixture of the polyglyceryl sebacate and the polyglycol sebacate with certain biocompatibility is used as the soft segment, and the mixture has good degradability and biocompatibility. The mixture can be naturally decomposed in biological applications, is non-toxic, and makes the synthesized polyurethane have wide application prospects in medical implants and shape recovery in vivo.

Description

Technical Field

[0001] This invention relates to a biodegradable polyurethane elastomer that can recover its shape at body temperature and its preparation method, belonging to the field of polymer biomaterials technology. Background Technology

[0002] Shape memory polymers (SMPs) are a class of smart materials capable of remembering temporary shapes and recovering their original shape in response to external stimuli. This is primarily manifested in their deformability and shape recovery, essentially their memory function—a cycle of "memorizing the initial state - fixing the deformation - recovering the initial state." In recent years, they have shown great application potential in medical devices, aerospace, and flexible electronics. The ability to recover shape at body temperature means these materials can be used in medical implants, biomedicine, and other applications requiring shape recovery within or near body temperature. As a smart material, shape memory polymers (SMPs) can change their shape in response to various stimuli, such as temperature, light, electricity, magnetism, and pH. To date, SMPs have been widely used in biomedical devices, such as cardiovascular stents, drug-eluting stents, sutures, aneurysm treatment devices, clot removal devices, controlled drug release matrices, tissue engineering, and bone tissue engineering. Among these, shape memory polyurethane (SMPU) has shown many advantages in biomedical device applications due to its excellent biocompatibility, biodegradability, wide shape recovery temperature range, and shape recovery rate.

[0003] Traditional polyurethane elastomers are typically synthesized from non-degradable monomers, resulting in their non-degradability. For medical implants, this non-degradability necessitates secondary surgery for removal, causing significant inconvenience. Therefore, the development of a fully degradable polyurethane elastomer has become an important goal. Selecting degradable monomers or polymers as raw materials ensures that the material can decompose in the natural biological environment after use and is non-toxic. Simultaneously, by controlling the structure to keep its shape transition temperature around body temperature, it can meet the performance design requirements of various intelligent medical implants. Therefore, developing a biodegradable polyurethane that can be implanted in the body and whose shape can recover at body temperature, along with its preparation method, is of great significance in this field. Summary of the Invention

[0004] The purpose of this invention is to address the limitations of traditional shape memory polyurethane materials being non-degradable and to meet the needs of specific application fields. This invention provides a degradable polyurethane elastomer whose shape can be restored at body temperature and its preparation method. The preparation method uses polyglycerol sebate (PGS) and polydiol sebate prepolymers as the soft segments of polyurethane and obtains the shape memory polyurethane material through an isocyanate crosslinking reaction.

[0005] To achieve the above objectives, the present invention provides a biodegradable polyurethane elastomer whose shape can recover at body temperature. The biodegradable polyurethane elastomer is prepared by using poly(glycerol sebate) prepolymer (PGS) and poly(diol sebate) prepolymer as the soft segments of the polyurethane via an isocyanate crosslinking reaction. The biodegradable polyurethane elastomer contains a chemical structural formula or chemical structural fragment as shown in Formula I.

[0006]

[0007] In Formula I, x, y, and z represent the average degree of polymerization, with values ​​of x≤1000, y≤1000, and z≤1000, respectively; R1 is selected from at least one of phenyl, methylene diphenyl, cyclohexyl, methylene dicyclohexyl, and C4-C8 alkyl groups; R2 is H or a polymer chain (the polymer chain refers to the ester polymer chain formed by the hydroxyl group in glycerol and sebacic acid); m is an integer between 1 and 10; the polyurethane elastomer achieves its original shape recovery at body temperature by adjusting the ratio of polyglycerol sebacic acid prepolymer (PGS) and polydiol sebacic acid prepolymer.

[0008] Preferably, the raw materials also include a chain extender.

[0009] Preferably, the chain extender is a diol and / or a diamine-based small molecule chain extender; the diol-based small molecule chain extender is at least one selected from 1,4-butanediol, ethylene glycol, and propylene glycol; the diamine-based small molecule chain extender is at least one selected from ethylenediamine, propylenediamine, and butanediamine.

[0010] The present invention also provides a method for preparing the above-mentioned biodegradable polyurethane elastomer, comprising: mixing poly(glycerol sebacic acid) prepolymer (PGS) and poly(diol sebacic acid) prepolymer as raw materials, dissolving them in an organic solvent, and then adding a catalyst and isocyanate to carry out a crosslinking reaction under heating conditions to prepare the biodegradable polyurethane elastomer.

[0011] The chemical reaction equation for the reaction of poly(succinate) glycerol prepolymer and polyethylene glycol sebacic acid ester prepolymer with dicyclohexylmethane diisocyanate (4,4'-methylenebis(cyclohexyl isocyanate)) is as follows:

[0012]

[0013] The chemical reaction equation for the crosslinking of poly(succinate) glycerol prepolymer and polyethylene glycol sebacic acid ester prepolymer with dicyclohexylmethane diisocyanate (4,4'-methylenebis(cyclohexyl isocyanate)) using ethylenediamine as a chain extender is as follows:

[0014]

[0015] Preferably, the mass ratio of glycerol to sebacic acid in the polysaccharide glycerol resin prepolymer is 1:10-10:1.

[0016] Preferably, the diol in the polydiol sebacate prepolymer is at least one selected from ethylene glycol, 1,3-propanediol and 1,4-butanediol, 1,6-hexanediol, 1,10-decanediol and 2,3-butanediol;

[0017] And / or, the molecular weight of the polydiol sebacic acid ester prepolymer is between 1,000 and 10,000;

[0018] And / or, the molecular weight of the polysaccharide glycerol prepolymer is between 1,000 and 10,000.

[0019] Preferably, the isocyanate is at least one of the following: aromatic isocyanate MDI (4,4'-methylenebis(phenylisocyanate)), 1,4-Phenyldiisocyanate, and aliphatic isocyanate H12-MDI 4,4'-methylenebis(cyclohexyl isocyanate), 1,4-Cyclohexanediisocyanate, and 1,6-Hexanediisocyanate, with the chemical formula shown below:

[0020]

[0021] Preferably, the mass ratio of the polysaccharide glycerol resin prepolymer to the polydiol sebacate prepolymer is 1:9-9:1;

[0022] And / or, the heating reaction is carried out at a temperature of 40-100°C for a time of 0.5-8 hours.

[0023] Preferably, the organic solvent is at least one of the following organic solvents: toluene, dimethyl sulfoxide (DMSO), tetrahydrofuran, N,N-dimethylformamide (DMF), N,N-dimethylacetamide (DMAC), and methyl isobutyl ketone (MIBK);

[0024] And / or, the catalyst is at least one of dibutyltin dilaurate, stannous octoate, and bismuth neodecanoate;

[0025] Preferably, the amount of catalyst used is 0.005-0.05 wt% of the total amount of all materials.

[0026] Preferably, it further includes adding a chain extender to carry out a further crosslinking reaction to improve the mechanical properties of the biodegradable polyurethane elastomer.

[0027] Technical principle of the invention:

[0028] In this invention, the polyurethane elastomer is a block polymer composed of two polymeric materials with different glass transition temperatures. In one molecule, two or more components are not completely miscible, leading to phase separation. The portion with the lower glass transition temperature is called the soft segment, and the portion with the higher glass transition temperature is called the hard segment. In this invention, polyester polyol serves as the soft segment, and isocyanate and chain extender serve as the hard segment. Generally, the soft segment is an amorphous segment acting as the reversible phase for shape memory, while the hard segment is a crystalline segment acting as the physical crosslinking point acting as the stationary phase. The soft segment of polyurethane has a significant impact on its glass transition temperature. The polydiol sebacic acid ester used in this invention has strong crystallinity, while polysaccharide glycerol has relatively poor crystallinity. By appropriately adjusting the ratio of the two, it is possible to restore its original shape at body temperature.

[0029] This invention uses a mixture of polysaccharide glycerol and polydiol sebaccharide, which have certain biocompatibility, as the soft segment. It has good degradability and biocompatibility, and can decompose naturally in biological applications. It is non-toxic, which makes the synthesized polyurethane have broad application prospects in medical implants and in the restoration of shape in the body.

[0030] The chemical structure of polyurethane has a significant impact on its performance. In this invention, polysaccharide glycerol with a high number of hydroxyl groups is used as one of the soft segments. Its abundant hydroxyl groups and ester bonds on the surface endow it with certain hydrophilicity and rapid degradation ability, resulting in a significantly higher hydrolysis rate compared to traditional polyurethanes synthesized from long-chain polyesters or polyethers. Simultaneously, due to its increased degradation rate, it exhibits a certain surface erosion mechanism, where large polymer molecules rapidly degrade into smaller molecules and are peeled off from the surface. This avoids the mass loss caused by bulk erosion in traditional biodegradable polyurethanes, which lags far behind its performance loss.

[0031] Compared with the prior art, the present invention has the following beneficial effects:

[0032] (1) The shape memory polyurethane biodegradable elastomer prepared by the present invention has good environmental friendliness. The polyester material is completely biodegradable, which means that it can decompose in the natural environment. Especially for medical implants, it can avoid secondary removal.

[0033] (2) In this invention, shape memory polyurethane is made from raw materials that are biodegradable and biocompatible, giving it good non-toxicity and medical application prospects.

[0034] (3) In this invention, polysaccharide glycerol is used as a polymer monomer. Polysaccharide glycerol has a large number of hydroxyl groups and ester bonds, which greatly improves its hydrolysis rate and exhibits a certain surface erosion mechanism, thus avoiding the mass loss caused by the bulk erosion of traditional biodegradable polyurethane which is far behind its performance loss.

[0035] (4) The present invention introduces a highly crystalline biodegradable segment of polydiol sebacic acid ester, which enables the polyurethane to quickly return to its original shape at body temperature. This gives it potential advantages in the medical field and biomedical applications, such as for use in biodegradable scaffolds, sutures, implants or medical devices. Attached Figure Description

[0036] Figure 1 This is an exemplary synthetic route for preparing a biodegradable polyurethane elastomer that can recover its shape at body temperature, as described in this invention. Detailed Implementation

[0037] To make the present invention more apparent and understandable, preferred embodiments are described in detail below with reference to the accompanying drawings.

[0038] The reagents used in the following embodiments of the present invention are all commercially available products.

[0039] The polysaccharide glycerol polyester polyol used in the following embodiments of the present invention is a polysaccharide glycerol polyester prepolymer, which is a prepolymer (molecular weight 3000) formed by the preliminary polymerization of sebacic acid monomer (molecular weight 202) and glycerol monomer (molecular weight 92), with some unreacted hydroxyl groups remaining in the glycerol monomer; similarly, the polydiol sebacic acid ester polyol is a polydiol sebacic acid ester prepolymer (molecular weight 3000).

[0040] Example 1

[0041] A method for preparing a fully biodegradable polyurethane elastomer that can recover its shape at body temperature includes the following steps:

[0042] (1) Weigh 10g of polysaccharide glycerol polyester polyol and 10g of polydiol sebaccharide polyol and add them to the reaction vessel.

[0043] (2) Add 40g of dimethylacetamide (DMACs) to dissolve the polyester polyol mixture.

[0044] (3) Introduce 0.05% bismuth neodecanoate and stir until homogeneous.

[0045] (4) Heat to 55°C and add 10 g of H12-MDI (4,4'-methylenebis(cyclohexylisocyanate)), and stir under nitrogen for 2 h.

[0046] (5) Cool to 40°C.

[0047] (6) Prepare 1 gram of ethylenediamine in an Erlenmeyer flask and dissolve it in 40.0 grams of dimethylacetamide solution.

[0048] (7) Add the solution dropwise into the prepolymer solution in the reaction vessel using a dropping funnel while stirring vigorously.

[0049] (8) When adding ethylenediamine solution, check the viscosity to see if an additional amount of solution is needed.

[0050] (9) After polymerization is complete, add 2g of 1,4-butanediol dissolved in 5g of dimethylacetamide and react for 1h.

[0051] (10) After removing the solvent, a biodegradable polyurethane with a body temperature-dependent shape is obtained.

[0052] Testing showed that the polyurethane prepared above could recover 90% of its shape after 1 minute at 37°C and 99% after 2 minutes. Furthermore, after 12 weeks of degradation in PBS solution, the resin showed stable weight loss with a cumulative loss of 70%, demonstrating strong degradability and shape recovery at body temperature.

[0053] Example 2

[0054] A method for preparing a fully biodegradable polyurethane elastomer that can recover its shape at body temperature includes the following steps:

[0055] (1) Weigh 10g of polysaccharide glycerol polyester polyol and 10g of polydiol sebaccharide polyol and add them to the reaction vessel.

[0056] (2) Add 40g of dimethylacetamide (DMACs) to dissolve the polyester polyol mixture.

[0057] (3) Heat to 55°C and add 20 g of H12-MDI, and stir under nitrogen for 30 min to obtain the prepolymer.

[0058] (4) Introduce 0.05% bismuth neodecanoate and stir at 55°C for 2 hours for further polymerization and crosslinking.

[0059] (5) Prepare 1 gram of ethylenediamine in an Erlenmeyer flask and dissolve it in 40.0 grams of dimethylacetamide solution.

[0060] (6) Add the solution dropwise to the prepolymer solution in the reaction vessel using a dropping funnel while stirring vigorously.

[0061] (7) When adding ethylenediamine solution, check the viscosity to see if an additional amount of solution is needed.

[0062] (8) After polymerization is complete, add 2g of 1,4-butanediol dissolved in 5g of dimethylacetamide and react for 1h.

[0063] (9) After removing the solvent, a biodegradable polyurethane with a body temperature-dependent shape is obtained.

[0064] Testing showed that the polyurethane prepared above could recover 95% of its shape after 2 minutes at 37°C. Furthermore, after 15 weeks of degradation in PBS solution, the resin showed stable weight loss with a cumulative loss of up to 50%, demonstrating strong degradability and shape recovery at body temperature.

[0065] Example 3

[0066] A method for preparing a fully biodegradable polyurethane elastomer that can recover its shape at body temperature includes the following steps:

[0067] (1) Weigh 10g of polysaccharide glycerol polyester polyol and 10g of polydiol sebaccharide polyol and add them to the reaction vessel.

[0068] (2) Add 40g DMF to dissolve the polyester polyol mixture.

[0069] (3) Introduce 0.05% bismuth neodecanoate as a catalyst and stir until homogeneous.

[0070] (4) Heat to 55°C and add 15 g of H12-MDI, and stir under nitrogen for 5 h.

[0071] (5) After removing the solvent, a biodegradable polyurethane with a body temperature-dependent shape is obtained.

[0072] Testing showed that the polyurethane prepared above could recover 70% of its shape after 1 minute at 37°C and 90% after 2 minutes. Furthermore, after 10 weeks of degradation in PBS solution, the resin showed a cumulative degradation mass of 80%, demonstrating strong degradability and shape recovery even at body temperature.

[0073] Example 4

[0074] A method for preparing a fully biodegradable polyurethane elastomer that can recover its shape at body temperature includes the following steps:

[0075] (1) Weigh 20g of polysaccharide glycerol polyester polyol and 10g of polydiol sebaccharide polyol and add them to the reaction vessel.

[0076] (2) Add 80g of dimethylacetamide (DMACs) to dissolve the polyester polyol mixture.

[0077] (3) Introduce 0.05% bismuth neodecanoate and stir until homogeneous.

[0078] (4) Heat to 55°C and add 30 g of H12-MDI, and stir under nitrogen for 6 h.

[0079] (5) After removing the solvent, a biodegradable polyurethane with a body temperature-dependent shape is obtained.

[0080] Testing showed that the polyurethane prepared above could recover 90% of its shape after 3 minutes at 37°C. Furthermore, after 10 weeks of degradation in PBS solution, the resin showed stable weight loss, with a cumulative loss of 60%, demonstrating strong degradability and shape recovery at body temperature.

[0081] The above description is merely a preferred embodiment of the present invention and is not intended to limit the present invention in any form or substance. It should be noted that those skilled in the art can make several improvements and additions without departing from the present invention, and these improvements and additions should also be considered within the scope of protection of the present invention.

Claims

1. A biodegradable polyurethane elastomer that recovers its shape at body temperature, characterized in that, The biodegradable polyurethane elastomer is prepared by using polyglycerol sebacate prepolymer (PGS) and polydiol sebacate prepolymer as soft segments of polyurethane via an isocyanate crosslinking reaction. The biodegradable polyurethane elastomer contains a chemical structural formula or chemical structural fragment as shown in Formula I. Formula I; In Formula I, x, y, and z represent the average degree of polymerization, with values ​​of x≤1000, y≤1000, and z≤1000, respectively; R1 is selected from at least one of phenyl, methylene diphenyl, cyclohexyl, methylene dicyclohexyl, and C4-C8 alkyl groups; R2 is H; and m is an integer between 1 and 10.

2. The biodegradable polyurethane elastomer as described in claim 1, characterized in that, The raw materials also include chain extenders.

3. The biodegradable polyurethane elastomer as described in claim 2, characterized in that, The chain extender is a diol and / or a diamine-based small molecule chain extender; the diol-based small molecule chain extender is at least one of 1,4-butanediol, ethylene glycol, and propylene glycol; the diamine-based small molecule chain extender is at least one of ethylenediamine, propylenediamine, and butanediamine.

4. The method for preparing the biodegradable polyurethane elastomer according to any one of claims 1 to 3, characterized in that, include: A biodegradable polyurethane elastomer was prepared by mixing polyglycerol sebacate prepolymer (PGS) and polydiol sebacate prepolymer, dissolving them in an organic solvent, and then adding a catalyst and isocyanate under heating conditions to carry out a crosslinking reaction.

5. The preparation method according to claim 4, characterized in that, The mass ratio of glycerol to sebacic acid in the polysaccharide prepolymer (PGS) is 1:10-10:

1.

6. The preparation method according to claim 4, characterized in that, The diol in the polydiol sebacic acid ester prepolymer is at least one selected from ethylene glycol, 1,3-propanediol, 1,4-butanediol, 1,6-hexanediol, 1,10-decyl alcohol, and 2,3-butanediol. And / or, the molecular weight of the polydiol sebacic acid ester prepolymer is between 1,000 and 10,000; And / or, the molecular weight of the polysaccharide glycerol prepolymer is between 1,000 and 10,000.

7. The preparation method according to claim 4, characterized in that, The isocyanate is at least one of the following: aromatic isocyanate 4,4'-diphenylmethane diisocyanate, terephthalic diisocyanate, and aliphatic isocyanate dicyclohexylmethane diisocyanate, 1,4-cyclohexyl diisocyanate, and 1,6-hexyl diisocyanate.

8. The preparation method according to claim 4, characterized in that, The mass ratio of the polyglycerol sebacate prepolymer (PGS) to the polydiol sebacate prepolymer is 1:9-9:1; And / or, the reaction is carried out at a temperature of 40-100°C for a time of 0.5-8 hours.

9. The preparation method according to claim 4, characterized in that, The organic solvent is at least one selected from toluene, dimethyl sulfoxide, tetrahydrofuran, N,N-dimethylformamide, N,N-dimethylacetamide, and methyl isobutyl ketone; And / or, the catalyst is at least one of dibutyltin dilaurate, stannous octoate, and bismuth neodecanoate.

10. The preparation method according to claim 4, characterized in that, Also includes: Chain extenders are added to further crosslink the reaction, thereby improving the mechanical properties of biodegradable polyurethane elastomers.

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