An injectable polyurethane material, a method for preparing the same and use thereof

Abstract

This invention provides an injectable polyurethane material, its preparation method, and its applications, belonging to the field of injectable materials. The injectable polyurethane material has a cross-linked polyurethane structure and hydrophilicity. It is formed by polymerizing a polyethylene glycol-diisocyanate prepolymer, a cross-linking agent, and a chain extender. The cross-linking agent has a structure of Formula 1, and the chain extender has a structure of Formula 2. Specifically, this invention can employ a cross-linking agent containing a Schiff base and a chain extender with catechol as a side group, introducing both into a polyurethane network to form the injectable polyurethane material. In this invention, this cross-linked hydrophilic polyurethane can utilize the pH-responsiveness of the Schiff base to achieve controlled injection through secondary processing; moreover, it has good mechanical properties, facilitating its application.

Description

Technical Field

[0001] This invention relates to the field of injectable materials, and particularly to an injectable polyurethane material, its preparation method, and its applications. Background Technology

[0002] In the fields of biochemistry and medicine, injectable materials, such as adhesives, fillers, and wound dressings, are used in various applications. Currently, there are two main injection mechanisms: shear thinning and in-situ gelation. Shear thinning generally works by causing chain dissociation and orientation in materials under shear force, resulting in a decrease in viscosity and allowing injection. After injection, the disappearance of the shear force allows the molecular chains to reassemble and recover. Shear-thinning materials are sensitive to shear force, and their network structure typically contains numerous physical interactions, often exhibiting instability and weak strength. These materials are usually composed of natural polymers, such as polysaccharides, peptides, and gelatin. Not only do these polymers have poor mechanical properties and limited chemical modification capabilities, but they also pose risks of immunogenicity and degradation. Furthermore, due to their poor flowability after leaving the injection needle, they are difficult to fully fill and bond in narrow areas.

[0003] In-situ gels involve injecting precursors into the target site, causing the precursors to polymerize and solidify through in-situ chemical reactions. The chemical reactions involved are typically photothermal-initiated free radical polymerization and fast-reaction addition reactions. In-situ gel materials form polymer networks through the chemical reaction of precursors. These precursors are usually composed of monomers or prepolymers containing active groups, such as substances with double bonds or isocyanate groups. Therefore, these materials are unstable before polymerization and have potential toxicity. Furthermore, during polymerization, they often face uncontrollable solidification and ineffective polymerization due to the failure of reaction sites. In addition, under certain physiological conditions, photothermal-initiated polymerization faces limitations in accessibility and thermal damage; addition reaction polymerization requires thorough mixing of two or more components before use, and must be used immediately after mixing, otherwise the processing window will be missed, increasing operational complexity.

[0004] Other methods involve pH-controlled injection, primarily by introducing sulfonic acid or carboxylic acid groups into the side groups of the polymer molecular chain, causing it to lose protons under alkaline conditions and form anionic polyelectrolytes; or by introducing amines (primary, secondary, and tertiary amines) into the main chain and side groups, causing it to gain protons under acidic conditions and form cationic polyelectrolytes. The resulting anionic or cationic polyelectrolytes can dissolve or disperse in water, allowing for injection via a needle. While converting the polymer into a more water-compatible polyelectrolyte through pH control enables injection, it results in poorer mechanical properties. Summary of the Invention

[0005] To address the aforementioned shortcomings of existing injectable materials, this invention provides an injectable polyurethane material, its preparation method, and its applications. The injectable material provided by this invention possesses excellent mechanical properties and injection capability with controllable reaction rates.

[0006] This invention provides an injectable polyurethane material having a crosslinked polyurethane structure and hydrophilicity. The injectable polyurethane material is formed by polymerization of polyethylene glycol-diisocyanate prepolymer, crosslinking agent, and chain extender. The crosslinking agent has a structure of Formula 1, and the chain extender has a structure of Formula 2.

[0007]

[0008] In an embodiment of the present invention, the polyethylene glycol structure in the polyethylene glycol-diisocyanate prepolymer has an average molecular weight of 300 to 4000, and the diisocyanate structure is aliphatic.

[0009] In embodiments of the present invention, the polyethylene glycol structure in the polyethylene glycol-diisocyanate prepolymer has an average molecular weight of 600 to 2500, and the diisocyanate structure is a hexamethylene diisocyanate structure, a dicyclohexylmethane diisocyanate structure, or an isophorone diisocyanate structure.

[0010] In an embodiment of the present invention, the injectable polyurethane material is in a viscous state in an acidic aqueous solution and recovers its elastic state in an injection environment with a pH value ≥ 7.

[0011] This invention provides a method for preparing the injectable polyurethane material as described above, comprising:

[0012] Diisocyanate and polyethylene glycol are reacted in a solvent to obtain polyethylene glycol-diisocyanate prepolymer; then a crosslinking agent having the structure of Formula 1 and a chain extender having the structure of Formula 2 are added for polymerization; after polymerization is completed, the solvent is removed to obtain the injectable polyurethane material.

[0013]

[0014] In an embodiment of the present invention, the reaction of the diisocyanate with polyethylene glycol is carried out in the presence of an organotin catalyst, wherein the organotin catalyst is dibutyltin dilaurate or dioctyltin diisooctanoate; the solvent is N,N'-dimethylformamide or dimethyl sulfoxide; the reaction temperature of the diisocyanate with polyethylene glycol is 60-80°C and the time is 1-3 hours.

[0015] In embodiments of the present invention, the mass ratio of the crosslinking agent to polyethylene glycol is 0.1 to 0.15:1, and the mass ratio of the chain extender to polyethylene glycol is 0.05 to 0.1:1.

[0016] In an embodiment of the present invention, the polymerization temperature is 60-80°C and the time is 15-30 hours; after removing the solvent, the mixture is soaked in water to reach equilibrium, and the desired product is obtained.

[0017] This invention provides the use of injectable polyurethane materials as adhesives, fillers, or wound dressings as described above.

[0018] In an embodiment of the present invention, the injectable polyurethane material is injected underwater via a pH-responsive method.

[0019] This invention designs and synthesizes a novel injectable polyurethane material, which is a cross-linked hydrophilic polyurethane. Specifically, it employs a cross-linking agent containing a Schiff base (structure shown in Formula 1, abbreviated as DDIMB) and a chain extender with catechol as a side group (structure shown in Formula 2), and introduces both into a polyurethane network to form the injectable polyurethane material. In this invention, this cross-linked hydrophilic polyurethane can utilize the pH-responsiveness of the Schiff base to achieve controlled injection through secondary processing; moreover, it has good mechanical properties, which is beneficial for applications.

[0020] Existing injectable polyelectrolyte materials have a narrow range of network structure control due to the need for specific structures and numbers of groups, and they cannot be mixed with polymers containing trans groups. For example, monomers or polymers with carboxyl groups cannot be used together with monomers or polymers containing amino groups. Moreover, after being converted into polyelectrolytes, they usually dissolve directly in water or disperse in water in the form of micelles due to their significant affinity for water, resulting in underwater instability and making underwater injection impossible.

[0021] The injectable polyurethane material described in this invention is a pH-responsive hydrophilic material that can achieve good mechanical properties and a controllable curing process while also being capable of underwater injection. Attached Figure Description

[0022] To more clearly illustrate the technical solutions of the embodiments of the present invention, the accompanying drawings used in the embodiments will be briefly introduced below. It should be understood that the following drawings only show some embodiments of the present invention and should not be regarded as a limitation of the scope. For those skilled in the art, other related drawings can be obtained based on these drawings without creative effort.

[0023] Figure 1 This is a schematic diagram of the preparation process in Example 1 of this application;

[0024] Figure 2 The loss factor and physical images of the sample before and after injection in Example 2 of this application are shown.

[0025] Figure 3 The in-situ NMR spectrum of the DDIMB and DHHM mixture in Example 2 of this application;

[0026] Figure 4 This is a graph showing the shear modulus curves of the sample at different pH values ​​and times in Example 3 of this application;

[0027] Figure 5 This shows the adhesion of various materials to animal organs in the sample of Example 4 of this application;

[0028] Figure 6 The adhesion strength test results are from Example 4 of this application;

[0029] Figure 7 Stress-strain diagrams of the samples from Examples 1 and 5 of this application;

[0030] Figure 8 This is an application effect diagram of the sample in Example 6 of this application;

[0031] Figure 9 This is an application effect diagram of the sample in Example 9 of this application;

[0032] Figure 10 This is a diagram showing the application effect of the sample in Example 10 of this application. Detailed Implementation

[0033] To provide a clearer understanding of the technical features, objectives, and effects of the present invention, the technical solution of the present invention will now be described in detail with reference to specific embodiments. The described embodiments are only some embodiments of the present invention, and not all embodiments.

[0034] This invention provides an injectable polyurethane material having a crosslinked polyurethane structure and hydrophilicity. The injectable polyurethane material is formed by polymerization of a polyethylene glycol-diisocyanate prepolymer, a crosslinking agent, and a chain extender. The crosslinking agent has a structure of Formula 1, and the chain extender has a structure of Formula 2.

[0035]

[0036] The injectable polyurethane material provided by this invention has good mechanical properties and controllable injection capability, and has broad application prospects.

[0037] The injectable polyurethane material described in this invention is a cross-linked hydrophilic polyurethane, whose cross-linked polyurethane structure mainly comprises molecular chains formed by the condensation polymerization of polyethylene glycol and diisocyanate. This invention selects polyurethane (full name polyurethane, containing -NH-CO-O- groups) as the injection material because it possesses advantages such as molecular designability, ease of modification, mechanical tunability, and good biocompatibility, making it a promising polymer for injection.

[0038] That is, the injectable polyurethane material is formed by polymerization of polyethylene glycol-diisocyanate prepolymer, crosslinking agent and chain extender, wherein polyethylene glycol reacts with diisocyanate to form a prepolymer, which is referred to as polyethylene glycol-diisocyanate prepolymer including polyethylene glycol structure and diisocyanate structure.

[0039] The average molecular weight of the polyethylene glycol and its structure described in the embodiments of the present invention is preferably 300-4000, more preferably 600-2500. Furthermore, the diisocyanate structure is preferably aliphatic, more preferably hexamethylene diisocyanate, dicyclohexylmethane diisocyanate, or isophorone diisocyanate.

[0040] In some embodiments, the structure of the polyethylene glycol-diisocyanate prepolymer is shown below:

[0041]

[0042] The hydrophilic crosslinking network of the injectable polyurethane material described in this embodiment of the invention includes: a crosslinking agent structure containing a Schiff base and a chain extender structure containing a catechol group. That is, the crosslinking agent involved contains a Schiff base group (-RC=N-, also called a Schiff base group) and a crosslinkable group, as shown in Formula 1; the crosslinking agent can be abbreviated as DDIMB, which is the abbreviation of N-(1,3-dihydroxypropan-2-yl)-4-(((1,3-dihydroxypropan-2-yl)imino)methyl)benzamide, and its Chinese name is N-(1,3-dihydroxypropyl-2)-4-(((1,3-dihydroxypropyl-2)imino)methyl)benzamide. The chain extender involved has the structure shown in Formula 2, and is further represented by DHHM (full name N-(3,4-dihydroxyphenethyl)-3-hydroxy-2-(hydroxymethyl)-2-methylpropanamide, N-(3,4-dihydroxyphenethyl)-3-hydroxy-2-(hydroxymethyl)-2-methylpropanamide; the single bond in the following formula is represented by methyl CH3):

[0043]

[0044] The injectable polyurethane material is an elastic material that can be acid-hydrolyzed in acidic aqueous solutions, changing its state from elastic to viscous. In its viscous state, it can be injected. Under injection conditions with pH ≥ 7, it can recover, returning from a viscous state to an elastic state, thus completing the injection. The state of this polyurethane material is determined by a loss factor. Specifically, during acid hydrolysis, the Schiff base structure of DDIMB decomposes into amino and aldehyde groups under acidic conditions, and can recover under neutral conditions (confirmed by in-situ NMR).

[0045] The response process of the injectable polyurethane material described in this embodiment of the invention is pH-controlled. During the recovery process, the recovery time can be controlled by adjusting the pH of the injection environment; that is, the higher the pH value, the shorter the recovery time, and thus the shorter the curing time. Therefore, controllable injection can be achieved. Furthermore, the material of this invention can be injected underwater.

[0046] The cross-linked hydrophilic polyurethane material contains not only pH-responsive Schiff base structures but also catechol structures. Hydrophobic interactions and π-π interactions occur between the catechol structures. These two physical interactions, together with the dynamic chemical cross-linking provided by DDIMB, can regulate the mechanical properties of the polyurethane.

[0047] This invention provides a method for preparing the injectable polyurethane material as described above, comprising:

[0048] Diisocyanate and polyethylene glycol are reacted in a solvent to obtain polyethylene glycol-diisocyanate prepolymer; then a crosslinking agent having the structure of Formula 1 and a chain extender having the structure of Formula 2 are added for polymerization; after polymerization is completed, the solvent is removed to obtain the injectable polyurethane material.

[0049]

[0050] In this embodiment of the invention, polyethylene glycol (PEG) is dissolved in a solvent, and a diisocyanate and preferably a catalyst are added to carry out a polycondensation reaction. The average molecular weight of the PEG is preferably 300–4000, more preferably 600–2500, and further preferably 1000–2000. The diisocyanate is preferably an aliphatic diisocyanate, more preferably hexamethylene diisocyanate (HDI), dicyclohexylmethane diisocyanate (HMDI), or isophorone diisocyanate (IPDI), and further preferably HDI or IPDI, which is beneficial for improving the biocompatibility and mechanical properties of the material.

[0051] The preferred catalyst is an organotin catalyst, which facilitates the reaction. The organotin catalyst is preferably dibutyltin dilaurate (DBTDL) or dioctyltin diisooctanoate, more preferably DBTDL; the solvent is N,N'-dimethylformamide (DMF) or dimethyl sulfoxide (DMSO). Specifically, the catalyst dosage is 0.2% to 2% (mass ratio) of the added solute. The reaction temperature of the diisocyanate with polyethylene glycol is 60 to 80°C, preferably 65 to 75°C; the reaction time is 1 to 3 hours, preferably 2 hours. Furthermore, the PEG / diisocyanate ratio is 1 / 2 to 1 / 4 (molar ratio); the molecular weight of the resulting prepolymer is 500 to 5000.

[0052] Subsequently, in this embodiment of the invention, DDIMB and DHHM are added to the above reaction system for polymerization (specifically, a solution containing DDIMB and DHHM can be added). After polymerization is completed, the solvent is removed, and the mixture is soaked in water to reach equilibrium to obtain a cross-linked hydrophilic polyurethane, which is the injectable polyurethane material.

[0053] The structures and main functions of DDIMB and DHHM described in this invention embodiment are as previously stated; they can be synthesized using conventional methods. DDIMB can be prepared by reacting p-formylbenzoic acid and 2-amino-1,3-propanediol; DHHM can be synthesized using 2,2'-dimethylolpropionic acid and other raw materials. The preferred molar ratio of the crosslinking agent DDIMB to polyethylene glycol is 0.5–1:1, and the preferred molar ratio of the chain extender to polyethylene glycol is 1–2:1.

[0054] In this embodiment of the invention, polymerization reaction can be carried out at a temperature of 60-80°C, and the reaction time is preferably 15-30 h, further preferably 20 h, to obtain a crosslinked polyurethane solution; the solvent in the solution is removed, and then it is soaked in water until equilibrium is reached (the mass no longer changes), thus obtaining the product.

[0055] This invention provides the application of the injectable polyurethane material as an adhesive, filler, or wound dressing, as described above; preferably, the injectable polyurethane material is pH-responsive for underwater injection. The injectable polyurethane material prepared in the embodiments of this invention has a pH-responsive Schiff base structure, a catechol structure, and a hydrophilic group structure, etc., exhibiting good mechanical properties and controllable injection achieved through secondary processing.

[0056] In some embodiments, the catechol structure of the injectable polyurethane material provides hydrophobic interactions and π-π interactions, thereby endowing the polyurethane with self-healing and self-adhesive capabilities. Combined with the aforementioned injectability, this cross-linked hydrophilic polyurethane can be used as an adhesive and filler. First, the polyurethane's inherent adhesive properties allow it to adhere to various object surfaces; second, after acid hydrolysis, the polyurethane can fill irregular surfaces, and after recovery, it can achieve both filling and sealing.

[0057] In other embodiments, based on the bioactivity of catechol, the cross-linked hydrophilic polyurethane has the functions of rapid hemostasis and promoting wound healing, and can be used as a hemostatic wound dressing and a wound healing promoting dressing.

[0058] To better illustrate the present invention, further examples are provided below. In the examples, all original reagents and materials are commercially available, and experimental methods without specific experimental conditions are conventional methods and conditions well known in the art.

[0059] The synthesis of DDIMB is as follows: p-Formylbenzoic acid (5.0 g) was completely dissolved in DMF (50 mL). 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (13.0 g) was slowly added to the above solution with stirring, followed by N-hydroxysuccinimide (6.0 g). The reaction was carried out at 25 °C for 12 h. After the reaction was complete, deionized water (500 mL) was added, and the mixture was allowed to stand for 2 h. The residue was then filtered and dried under vacuum. The completely dried residue (2.0 g) was dissolved in DMSO (10 mL), stirred, and then added to a 2-amino-1,3-propanediol / DMSO (2.0 g / 10 mL) solution. Anhydrous magnesium sulfate (2.0 g) was added, and the reaction was carried out at 25 °C for 12 h. After the reaction was complete, the mixture was filtered, and the filtrate was collected. The crude product was recrystallized from methanol after vacuum distillation. Finally, the precipitate was filtered, collected, and vacuum dried to obtain white powdered DDIMB with a final yield of 62%.

[0060] The synthesis of DHHM was as follows: 2,2'-di(hydroxymethyl)propionic acid (2.0 g) and concentrated sulfuric acid (200 μL) were dissolved in acetone (100 mL), and the mixture was reacted at 25 °C for 12 h. After the reaction was complete, triethylamine (1.0 mL) was added to the above reaction solution and the mixture was stirred for 30 min to neutralize the solution. Then, the acetone was removed by rotary evaporation, and the crude product was completely dissolved in dichloromethane (30 mL). The solution was then washed three times with deionized water (20 mL). Anhydrous magnesium sulfate was added to the organic phase, and after 30 min, the mixture was filtered and rotary evaporated to obtain a concentrated pale yellow solution. This pale yellow solution was redissolved in dichloromethane (20 mL), and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (4.0 g) and N-hydroxysuccinimide (2.5 g) were added. The mixture was reacted at 25 °C for 12 h. After the reaction was complete, the mixture was washed three times with deionized water (20 mL). Anhydrous magnesium sulfate was added to the organic phase, and after 30 min, the mixture was filtered and rotary evaporated to obtain a white solid. This white solid was dissolved in dichloromethane / methanol (15 mL / 15 mL), and dopamine hydrochloride (4.0 g) and triethylamine (2.0 mL) were added. The mixture was reacted at 25 °C under a nitrogen atmosphere for 12 h. After the reaction was complete, the solution was concentrated, and then deionized water (100 mL) was added. The mixture was allowed to stand for 2 h, filtered, collected, and vacuum dried to obtain a brown solid. This brown solid was dissolved in methanol (20 mL), and trifluoroacetic acid (1.7 g) was added. The mixture was reacted at 25 °C under a nitrogen atmosphere for 12 h. All solvent was removed by rotary evaporation, and the mixture was dried in a vacuum oven for 24 h to obtain pure DHHM; yield 50%.

[0061] Example 1:

[0062] according to Figure 1The steps shown are as follows: First, 2.0 g of polyethylene glycol with a molecular weight of 1000 g / mol (polyethylene glycol with a molecular weight of 1000 g / mol is represented as PEG1000) is dissolved in 10 mL of N,N'-dimethylformamide (DMF). Then, 0.89 g of isophorone diisocyanate (IPDI) and 10 μL of dibutyltin dilaurate (DBTDL) are added, and the mixture is reacted at 70 °C for 2 h to obtain the prepolymer solution system (this is step 1).

[0063] Then, in step 2, 5 mL of a DMF solution containing 0.24 g DDIMB and 0.11 g DHHM was added to the above system, and the reaction was continued at 70 °C for 20 h to obtain a polyurethane solution. After removing the solvent, the solution was soaked in water until equilibrium was reached. The resulting injectable polyurethane material sample was denoted as DDIMB / DHHM / 1000_1 / 0.5.

[0064] The resulting injectable polyurethane material sample is in an elastic state at pH=7 and in a viscous state at pH=3, thus it can be injected; that is, controllable injection is achieved through a secondary processing method based on pH response.

[0065] Example 2:

[0066] according to Figure 2 Take 0.2g of DDIMB / DHHM / 1000_1 / 0.5 and put it into a syringe equipped with a 20G flat-angle needle. Do not inject at this time.

[0067] Add 3 mL of acetic acid aqueous solution with pH=3.0 to the syringe and acidify for 30 min. Then drain all the liquid. The acidified DDIMB / DHHM / 1000_1 / 0.5 can be injected into the target location through the needle (it is injectable at this time). After the injection is completed, the sample can be placed in an environment with pH=7 for 5 min to restore its elastic shape.

[0068] Figure 2 The study also shows the loss factor of the polyurethane material sample under certain conditions; the loss factor was tested using a rotational rheometer equipped with a 25 mm diameter stainless steel flat rotor and a temperature-controlled quartz substrate. The sample was placed on the substrate and the rotor was moved to a position 1.5 mm from the substrate; the extruded sample was then removed using a scraper. The results were obtained in the range of 0.1–100 rad·s. -1 A 1% strain was applied during the frequency scanning test to obtain the loss factor curve. Figure 2 In the diagram, the curves of different colors represent the loss factor curves obtained by immersing the acid-hydrolyzed polyurethane in deionized water for different times. As the immersion time increases, the loss factor gradually decreases, indicating that the polyurethane gradually changes from a viscous state to an elastic state; this confirms that the polyurethane gradually recovers under the condition of pH=7.

[0069] Figure 3 These are the in-situ NMR results of a mixture of DDIMB and DHHM. First, DDIMB and DHHM were dissolved in DMSO-d6 at a strict molar ratio of 1 / 0.5. This DDIMB / DHHM mixture was used to equivalently replace DDIMB / DHHM / 1000_1 / 0.5, to avoid the influence of other hydrogen atoms in the polyurethane on the assessment of chemical structure changes. After acid hydrolysis with acetic acid, the NMR of the mixture showed a decrease in the intensity of the active hydrogen peak at 8.35 ppm on the carbon of the Schiff base, and a decrease in the intensity of the characteristic peak of hydrogen atoms on the benzene ring in DDIMB. Simultaneously, a characteristic peak of active hydrogen on the carbonyl carbon appeared at 10.1 ppm, accompanied by the appearance of characteristic peaks of hydrogen atoms on the benzene ring shifting to higher frequencies. All of these indicate that the Schiff base underwent partial cleavage, forming benzaldehyde and an amino group. After the mixture was completely freeze-dried, DMSO-d6 was added again to dissolve and restore it. Eventually, the active hydrogen on the carbonyl carbon disappeared, and the Schiff base reformed. The NMR of the restored mixture was the same as that before acid hydrolysis.

[0070] according to Figure 3 During the acid hydrolysis process, the chemical structural change of this cross-linked hydrophilic polyurethane from an elastic state to a viscous state was determined. Under acidic conditions, the Schiff base structure of DDIMB decomposes into amino and aldehyde groups, which can be restored under neutral conditions.

[0071] Example 3:

[0072] Take 0.2g of DDIMB / DHHM / 1000_1 / 0.5 and put it into a syringe equipped with a 20G flat-angle needle. Add 3mL of pH=3.0 acetic acid aqueous solution for acidification for 30min. Then drain all the liquid. The acidified DDIMB / DHHM / 1000_1 / 0.5 can be injected into the target location through the needle. After the injection, place the sample in an environment of pH=10 for 1min to restore its elastic shape.

[0073] and, Figure 4 These are shear modulus curves at different pH values ​​and times. The higher the pH value, the shorter the recovery time, also known as the curing time; this invention enables controlled injection.

[0074] Using a rotational rheometer at 1% strain, 1 rad·s -1 The following test was conducted, and the results were obtained. Figure 4 The different pH values ​​refer to the recovery process at different pH levels, which involves immersing the acid-hydrolyzed polyurethane in deionized water with varying pH values ​​for testing. As the ambient pH increases, the degree of recovery at the same time point improves; therefore, the time and extent of re-crosslinking can be arbitrarily controlled by altering the pH during the recovery period.

[0075] Example 4:

[0076] Apply 0.5g of DDIMB / DHHM / 1000_1 / 0.5 directly to the surface of various materials (no acid hydrolysis process; materials are used in patch form). See [link / reference]. Figure 5 It exhibits good adhesion to wood, glass, polypropylene, stainless steel, rubber, and animal tissues (heart, liver, stomach, lungs, kidneys).

[0077] according to Figure 5 This polyurethane exhibits excellent adhesion to various materials and animal organs. Furthermore, it conforms well to the curves of the fingers.

[0078] right Figure 5 Quantitative tests were conducted on the adhesion strength of different materials, and the test methods are as follows: Figure 6 The overlap test method shown (the obtained adhesion strength is the overlap strength); see results. Figure 6 The adhesion strength varies.

[0079] Example 5:

[0080] Following the steps of Example 1, a polyurethane material sample DDIMB / DHHM / 1000_1 / 0.25 was prepared, the difference being that the molar ratio of DDIMB / DHHM was 1:0.25.

[0081] The control group was DDIMB / DHHM / 1000_1 / 0.

[0082] Mechanical properties were tested on each sample, and the results are shown in [reference needed]. Figure 7 The resulting injectable material has good mechanical properties.

[0083] Compared to existing injectable materials (elongation at break less than 300% and fracture strength less than 100 kPa), the mechanical properties of this application are at a higher level (elongation at break can reach 680% and fracture strength 280 kPa).

[0084] Example 6:

[0085] 0.2g of DDIMB / DHHM / 1000_1 / 0.5 was placed in a syringe equipped with a 20G flat-angle needle. 3mL of pH 3.0 acetic acid aqueous solution was added for acidification for 30 minutes. All the liquid was then drained. The acidified DDIMB / DHHM / 1000_1 / 0.5 was injected into the bleeding site of the rat liver through the needle, achieving hemostasis within 1 minute. The blood pH was approximately 7.4, providing a recovery environment, while catechol accelerated clotting.

[0086] A 0.5 cm incision was made in the liver of a rat using a scalpel, and polyurethane was injected into the wound. Photos were taken at different time points; the results are shown below. Figure 8 The control group in the figure received no treatment after the wound was opened; after polyurethane was injected into the wound, hemostasis was achieved within 1 minute, while the control group, which received no treatment, required 5 minutes to achieve hemostasis.

[0087] Example 7:

[0088] 2.0 g of polyethylene glycol (PEG2000) with a molecular weight of 2000 g / mol was dissolved in 15 mL of dimethyl sulfoxide (DMSO). 0.51 g of hexamethylene diisocyanate (HDI) and 10 μL of DBTDL were added, and the mixture was reacted at 70 °C for 2 h. Then, 5 mL of a DMSO solution containing 0.20 g of DDIMB and 0.18 g of DHHM was added, and the reaction was continued at 70 °C for 20 h to obtain a polyurethane solution. After removing the solvent, the solution was immersed in water until equilibrium was reached. The sample was labeled DDIMB / DHHM / 2000_1 / 1.

[0089] Example 8:

[0090] Take 0.2g of DDIMB / DHHM / 2000_1 / 1 and put it into a syringe equipped with a 20G flat-angle needle. Add 3mL of trifluoroacetic acid aqueous solution with pH=3.0 and acidify for 10min. Then drain all the liquid. The acidified DDIMB / DHHM / 2000_1 / 1 can be injected into the target location through the needle. After the injection, place the sample in an environment with pH=7 and allow it to recover for 5min.

[0091] Example 9:

[0092] Take 0.2g of DDIMB / DHHM / 2000_1 / 1 and put it into a syringe equipped with a 20G flat-angle needle. Add 3mL of hydrochloric acid aqueous solution with pH=4.0 and acidify for 15min. Then drain all the liquid. The acidified DDIMB / DHHM / 2000_1 / 1 can be injected into the target location through the needle. After the injection, place the sample in an environment with pH=7 to recover for 5min.

[0093] The acid-hydrolyzed polyurethane (pH=3) was injected into the star-shaped region, and after recovery, the region was completely filled. See the results below. Figure 9 This demonstrates its potential to fill irregular areas and wounds. The polyurethane material of this invention can fill irregular surfaces and achieve filling and sealing after restoration.

[0094] Example 10:

[0095] 0.5g of DDIMB / DHHM / 2000_1 / 1 was placed in a syringe equipped with a 20G flat-angle needle, and 5mL of pH 3.0 acetic acid aqueous solution was added for acidification for 30 minutes. All the liquid was then drained. The acidified DDIMB / DHHM / 2000_1 / 1 was injected into the skin defect of rats through the needle, and the wound was slowly rinsed with 10mL of physiological saline. The wound was then bandaged. After 9 days, the wound area was significantly smaller than that of the experimental group that was only rinsed with physiological saline.

[0096] A 1cm incision was made in the skin of the rats, and acid-hydrolyzed polyurethane was injected into the wound. A saline group was used as a control. Wound healing was photographed at different time points, and the wound area was statistically analyzed. Results are shown below. Figure 10 The results showed that wounds treated with this polyurethane healed faster.

[0097] As can be seen from the above embodiments, from both the aspects of injection materials and injection mechanism, the cross-linked hydrophilic polyurethane structure of the present invention can utilize the pH-responsive capability of Schiff bases to achieve controllable underwater injection through secondary processing. Furthermore, it exhibits good mechanical properties and can be used as an adhesive, filler, or wound dressing, etc., showing broad application prospects.

[0098] The above examples are only used to illustrate the technical features and implementation process of the present invention, and are not intended to limit the technical solutions of the present invention. It should be noted that those skilled in the art can still make modifications or equivalent substitutions to the present invention without departing from the principle of the present invention, and all such modifications or substitutions are covered by the protection of the present invention.

Claims

1. An injectable polyurethane material, characterized in that, Having a cross-linked polyurethane structure and hydrophilicity, the injectable polyurethane material is formed by polymerization of polyethylene glycol-diisocyanate prepolymer, cross-linking agent and chain extender; the cross-linking agent has a structure of Formula 1 and the chain extender has a structure of Formula 2. The polyethylene glycol-diisocyanate prepolymer is formed by reacting polyethylene glycol with diisocyanate; the mass ratio of the crosslinking agent to polyethylene glycol is 0.1~0.15:1, and the mass ratio of the chain extender to polyethylene glycol is 0.05~0.1:

1. Formula 1, Formula 2.

2. The injectable polyurethane material according to claim 1, characterized in that, The polyethylene glycol-diisocyanate prepolymer has an average molecular weight of 300-4000 and an aliphatic diisocyanate structure.

3. The injectable polyurethane material according to claim 2, characterized in that, The polyethylene glycol-diisocyanate prepolymer has an average molecular weight of 600-2500 for the polyethylene glycol structure, and the diisocyanate structure is a hexamethylene diisocyanate structure, a dicyclohexylmethane diisocyanate structure, or an isophorone diisocyanate structure.

4. The injectable polyurethane material according to any one of claims 1-3, characterized in that, The injectable polyurethane material is viscous in an acidic aqueous solution and recovers its elastic state in an injection environment with a pH value ≥ 7.

5. The method for preparing the injectable polyurethane material according to any one of claims 1-4, characterized in that, include: Diisocyanate and polyethylene glycol are reacted in a solvent to obtain polyethylene glycol-diisocyanate prepolymer; then a crosslinking agent having the structure of Formula 1 and a chain extender having the structure of Formula 2 are added for polymerization; after polymerization is completed, the solvent is removed to obtain the injectable polyurethane material. The mass ratio of the crosslinking agent to polyethylene glycol is 0.1~0.15:1, and the mass ratio of the chain extender to polyethylene glycol is 0.05~0.1:

1. Formula 1, Formula 2.

6. The preparation method according to claim 5, characterized in that, The reaction of diisocyanate with polyethylene glycol is carried out in the presence of an organotin catalyst, wherein the organotin catalyst is dibutyltin dilaurate or dioctyltin diisooctanoate; the solvent is N,N'-dimethylformamide or dimethyl sulfoxide; the reaction temperature of diisocyanate with polyethylene glycol is 60~80℃ and the time is 1~3h.

7. The preparation method according to claim 6, characterized in that, The polymerization temperature is 60~80℃ and the time is 15~30h; after removing the solvent, the material is soaked in water to reach equilibrium, thus obtaining the injectable polyurethane material.

8. The use of the injectable polyurethane material as described in any one of claims 1-4 as an adhesive, filler, or in the preparation of wound dressings.

9. The application according to claim 8, characterized in that, The injectable polyurethane material is injected underwater via a pH-responsive method.

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