Injectable polyurethane material as well as preparation method and application thereof

Abstract

The invention provides an injectable polyurethane material as well as a preparation method and application thereof, and belongs to the field of injectable materials. The injectable polyurethane material has a cross-linked polyurethane structure and hydrophilicity, and the injectable polyurethane material is formed by polymerizing a polyethylene glycol-diisocyanate prepolymer, a cross-linking agent and a chain extender; the cross-linking agent has a structure as shown in a formula 1, and the chain extender has a structure as shown in a formula 2. The injectable polyurethane material can be formed by specifically adopting a cross-linking agent containing Schiff base and a chain extender taking catechol as a side group, and introducing the cross-linking agent containing Schiff base and the chain extender taking catechol as a side group into a polyurethane network. In the cross-linked hydrophilic polyurethane disclosed by the invention, the pH response capability of Schiff base can be utilized, and controllable injection can be realized through secondary processing; the mechanical property is good, and application is facilitated. # imgabs0 #

Description

Technical Field

[0001] The present invention relates to the field of injectable materials, and particularly to an injectable polyurethane material, a preparation method thereof, and an application thereof. Background Art

[0002] In the fields of biochemistry and medicine, injectable materials such as adhesives, fillers, wound dressings and other application products; there are currently two main injection mechanisms, including: shear thinning and in-situ gelation. Among them, the principle of shear thinning is generally that the material will undergo chain dissociation and orientation after being subjected to shear force, so that the viscosity of the material decreases and it can be injected through a syringe; after injection, the disappearance of the shear force allows the molecular chains to be reassembled and restored. Shear-thinning materials are sensitive to shear force, and their network structure usually contains a large number of physical interactions, so they often show instability and weak strength. Such materials are usually composed of natural polymers, such as polysaccharides, polypeptides, gelatin, etc. Not only do the polymers themselves have poor mechanical properties and poor chemical modification properties, but there are also risks of immunogenicity and deterioration. In addition, due to the poor fluidity of the material after leaving the injection needle, it is difficult to achieve sufficient filling and bonding in some narrow parts.

[0003] In-situ gelation is to inject a precursor at the target site, and cause the polymerization and curing of the precursor through an in-situ chemical reaction. The chemical reactions involved are usually free radical polymerization initiated by photothermal and addition reactions with a relatively fast reaction rate. In-situ gel materials form a polymer network through the chemical reaction of the precursor. Such precursors usually consist of monomers or prepolymers containing active groups, such as substances with groups such as double bonds and isocyanate groups. Therefore, such materials are not stable before polymerization and have certain potential toxicity; and during polymerization, they often face uncontrollable curing and ineffective polymerization caused by the failure of reaction sites. In addition, when used under some physiological conditions, photothermal-initiated polymerization will face limitations of 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 the complexity of the operation.

[0004] There are also other schemes for realizing injection through pH regulation, mainly by introducing groups such as sulfonic acid and carboxylic acid into the side groups of polymer molecular chains, so as to lose protons under alkaline conditions and form anionic polyelectrolytes; or introducing amines (primary, secondary, tertiary amines) on the main chain and side groups, so as to obtain protons under acidic conditions and form cationic polyelectrolytes. The formed anionic or cationic polyelectrolytes can be dissolved or dispersed in water, so as to be injected through a needle. The strategy of converting a polymer into a polyelectrolyte that is more compatible with water by means of pH regulation can achieve injection, but its mechanical properties are poor. Summary of the Invention

[0005] To solve the above-mentioned drawbacks of existing injectable materials, the present invention provides an injectable polyurethane material, its preparation method and its application. The injectable material provided by the present invention has good mechanical properties and an injection ability with a controllable reaction rate.

[0006] The present invention provides an injectable polyurethane material, which has a crosslinked polyurethane structure and hydrophilicity. The injectable polyurethane material is formed by polymerizing 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;

[0007]

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

[0009] In an embodiment of the present invention, the average molecular weight of the polyethylene glycol structure in the polyethylene glycol-diisocyanate prepolymer is 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 returns to an elastic state in an injection environment with a pH value ≥ 7.

[0011] The present invention provides a preparation method of the injectable polyurethane material as described above, including:

[0012] Reacting a diisocyanate with polyethylene glycol in a solvent to obtain a polyethylene glycol-diisocyanate prepolymer; then adding a crosslinking agent having a structure of formula 1 and a chain extender having a structure of formula 2 for polymerization, and removing the solvent after the polymerization is completed 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, and 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 to 80 °C, and the time is 1 to 3 h.

[0015] In an embodiment 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 temperature of the polymerization is 60-80 °C and the time is 15-30 h; after removing the solvent, it is soaked in water to reach equilibrium, and thus obtained.

[0017] The present invention provides the application of the injectable polyurethane material as described above as a binder, filler or wound dressing.

[0018] In an embodiment of the present invention, the injectable polyurethane material realizes underwater injection in a pH-responsive manner.

[0019] The present invention designs and synthesizes a novel injectable polyurethane material, which is a crosslinked hydrophilic polyurethane. Specifically, a crosslinking agent containing a Schiff base (the structure is shown in Formula 1, abbreviated as DDIMB) and a chain extender with catechol as a side group (the structure is shown in Formula 2) are used, and the two are introduced into the polyurethane network to form the injectable polyurethane material. In the present invention, this crosslinked hydrophilic polyurethane can utilize the pH-responsive ability of the Schiff base to achieve controllable injection through secondary processing; moreover, it has good mechanical properties and is conducive to application.

[0020] For existing injectable polyelectrolyte materials, due to the need for specific structures and numbers of groups, the regulation range of the network structure is relatively narrow, and they cannot be mixed with polymers with reactive 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, due to their significant affinity for water, they usually directly dissolve in water or are dispersed in water in the form of micelles, resulting in instability underwater and unable to perform underwater injection.

[0021] The injectable polyurethane material described in the present invention is a pH-responsive hydrophilic material, which can achieve good mechanical properties and a controllable curing process, and can perform underwater injection at the same time. Description of the Drawings

[0022] In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the following will briefly introduce the drawings required for the embodiments. It should be understood that the following drawings only show some embodiments of the present invention, and therefore should not be regarded as limiting the scope. For those of ordinary skill in the art, without creative efforts, other related drawings can also be obtained based on these drawings.

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

[0024] Figure 2 It is the loss factor and physical diagram before and after sample injection in Example 2 of this application;

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

[0026] Figure 4 It is the shear modulus curve graph of the samples in Example 3 of the present application at different pH values and different times;

[0027] Figure 5 It is the adhesion situation of the samples in Example 4 of the present application to various materials and animal organs;

[0028] Figure 6 It is the adhesion strength test result of Example 4 of the present application;

[0029] Figure 7 It is the stress-strain diagram of the samples in Example 1 and Example 5 of the present application;

[0030] Figure 8 It is the application effect diagram of the samples in Example 6 of the present application;

[0031] Figure 9 It is the application effect diagram of the samples in Example 9 of the present application;

[0032] Figure 10 It is the application effect diagram of the samples in Example 10 of the present application. Detailed implementation manners

[0033] In order to more clearly understand the technical features, objectives, and effects of the present invention, the technical solutions of the present invention will be described in detail below in conjunction with specific embodiments. The described embodiments are only a part of the embodiments of the present invention, rather than all of the embodiments.

[0034] The present invention provides an injectable polyurethane material, which has a crosslinked polyurethane structure and hydrophilicity. The injectable polyurethane material is formed by polymerizing 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 the present invention has good mechanical properties and an injectable ability with a controllable reaction rate, and has a wide application prospect.

[0037] The injectable polyurethane material described in the embodiments of the present invention is a crosslinked hydrophilic polyurethane, and the crosslinked polyurethane structure thereof mainly includes a molecular chain formed by polycondensation of polyethylene glycol and diisocyanate. In the embodiments of the present invention, this type of polymer (fully named polyurethane, containing -NH-CO-O- groups) is selected as the injection material because it has advantages such as molecular designability, easy modification, adjustable mechanics, and good biocompatibility, and is a promising injectable polymer.

[0038] That is, the injectable polyurethane material is formed by polymerizing a polyethylene glycol-diisocyanate prepolymer, a crosslinking agent, and a chain extender. Among them, polyethylene glycol reacts with diisocyanate to form a prepolymer, denoted as a polyethylene glycol-diisocyanate prepolymer including a polyethylene glycol structure and a diisocyanate structure.

[0039] In the embodiments of the present invention, the average molecular weight of the polyethylene glycol and its structure is preferably 300 to 4000, more preferably 600 to 2500. And, the diisocyanate structure is preferably aliphatic, more preferably a hexamethylene diisocyanate structure, a dicyclohexylmethane diisocyanate structure, or an isophorone diisocyanate structure.

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

[0041]

[0042] The polyurethane hydrophilic crosslinking network of the injectable polyurethane material described in the embodiments of the present 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 known as 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 the Chinese name is N-(1,3-dihydroxypropyl-2)-4-(((1,3-dihydroxypropyl-2)imino)methyl)benzamide. The structure of the chain extender involved is as shown in Formula 2, and further is DHHM (fully named N-(3,4-dihydroxyphenethyl)-3-hydroxy-2-(hydroxymethyl)-2-methylpropanamide, N-(3,4-dihydroxybenzyl)-3-hydroxy-2-(hydroxymethyl)-2-methylpropanamide; the single bond in the following formula represents methyl CH3):

[0043]

[0044] The injectable polyurethane material is an elastic material, which can be acid hydrolyzed in an acidic aqueous solution, and its state will change from an elastic state to a viscous state. In the viscous state, it can be injected; in an injection environment with pH≥7, it can be restored, that is, it changes back from the viscous state to the elastic state to complete the injection. Among them, the state of the polyurethane material is determined by the loss factor. Specifically, during the acid hydrolysis process, the Schiff base structure of DDIMB will decompose into amino and aldehyde groups under acidic conditions and can be restored under neutral conditions (confirmed by in-situ nuclear magnetic resonance).

[0045] In the embodiment of the present invention, the above response process of the injectable polyurethane material is pH-regulated. During the recovery process, the recovery time can be regulated by adjusting the pH of the injection environment, that is, the higher the pH value, the shorter the recovery time, and the so-called curing time is shorter. Therefore, controllable injection can be achieved. Further, the material of the present invention can be injected underwater.

[0046] In the crosslinked hydrophilic polyurethane material described above, in addition to containing a pH-responsive Schiff base structure, it also contains a catechol structure; hydrophobic interactions and π-π interactions will occur between the catechol structures, and these two physical interactions can jointly regulate the mechanical properties of the polyurethane with the dynamic chemical crosslinking provided by DDIMB.

[0047] The present invention provides a preparation method of the injectable polyurethane material as described above, including:

[0048] Reacting a diisocyanate with polyethylene glycol in a solvent to obtain a polyethylene glycol-diisocyanate prepolymer; then adding a crosslinking agent having the structure of formula 1 and a chain extender having the structure of formula 2 for polymerization, and removing the solvent after the polymerization is completed to obtain the injectable polyurethane material;

[0049]

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

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

[0052] Subsequently, in the embodiment of the present invention, DDIMB and DHHM were added to the above reaction system for polymerization (specifically, a solution dissolved with DDIMB and DHHM can be added). After the polymerization was completed, the solvent was removed, and after soaking and equilibration in water, a crosslinked hydrophilic polyurethane was obtained, which is the injectable polyurethane material described above.

[0053] The structures and main functions of DDIMB and DHHM in the embodiments of the present invention are as described above; they can be synthesized by conventional methods. Among them, DDIMB can be prepared by reacting p-formylbenzoic acid with 2-amino-1,3-propanediol; DHHM can be synthesized using 2,2'-dihydroxymethylpropionic acid and the like as raw materials. The molar ratio of the crosslinking agent DDIMB to polyethylene glycol is preferably 0.5-1:1, and the molar ratio of the chain extender to polyethylene glycol is preferably 1-2:1.

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

[0055] The present invention provides the application of the injectable polyurethane material as described above as an adhesive, filler or wound dressing; preferably, the injectable polyurethane material realizes underwater injection in a pH-responsive manner. The injectable polyurethane material prepared in the embodiment of the present invention has a Schiff base structure, a catechol structure, and a hydrophilic group structure that are pH-responsive, and has good mechanical properties and realizes controllable injection through secondary processing.

[0056] In some embodiments, the catechol structure of the injectable polyurethane material provides hydrophobic interaction and π-π interaction, thereby endowing the polyurethane with the ability of self-healing and self-adhesion. Combining the injectable ability mentioned above, this crosslinked hydrophilic polyurethane can be used as an adhesive and a filler. First, the adhesion ability possessed by the polyurethane itself can adhere to the surfaces of various objects; second, after acidolysis, the polyurethane can fill irregular surfaces and can achieve filling and sealing after recovery.

[0057] In other embodiments, based on the biological activity of catechol, this crosslinked hydrophilic polyurethane has the functions of rapid hemostasis and promoting wound healing, and can be used as a hemostatic wound dressing and a wound dressing for promoting healing.

[0058] To better illustrate the present invention, further examples are given below through embodiments. In the embodiments, all the original reagents and materials can be obtained commercially, and the 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 under stirring, and then N-hydroxysuccinimide (6.0 g) was added to the reaction system. The reaction was carried out at 25 °C for 12 h. After the reaction was completed, deionized water (500 mL) was added and allowed to stand for 2 h. The filter residue was collected by filtration and dried in vacuo. The completely dried filter residue (2.0 g) was dissolved in DMSO (10 mL), and after stirring, it was added to a solution of 2-amino-1,3-propanediol / DMSO (2.0 g / 10 mL). Anhydrous magnesium sulfate (2.0 g) was added, and the reaction was carried out at 25 °C for 12 h. After the reaction was completed, the filtrate was filtered and collected, and the crude product was recrystallized from methanol after distillation under reduced pressure. Finally, the precipitate was filtered, collected, and dried in vacuo to obtain white powdered DDIMB with a final yield of 62%.

[0060] The synthesis of DHHM is as follows: 2,2'-bis(hydroxymethyl)propionic acid (2.0 g) and concentrated sulfuric acid (200 μL) were dissolved in acetone (100 mL), and the reaction was carried out at 25 °C for 12 h. After the reaction was completed, triethylamine (1.0 mL) was added to the above reaction solution and stirring was continued for 30 min to neutralize the solution. Then acetone was removed by rotary evaporation, and the crude product was completely dissolved in dichloromethane (30 mL), and then washed with deionized water (20 mL) and separated by liquid-liquid extraction three times. The organic phase was taken, anhydrous magnesium sulfate was added, and after 30 min, filtration and rotary evaporation were carried out to finally obtain a concentrated pale yellow solution. The pale yellow solution was redissolved in dichloromethane (20 mL), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (4.0 g) and N-hydroxysuccinimide (2.5 g) were added, and the reaction was carried out at 25 °C for 12 h. After the reaction was completed, it was washed with deionized water (20 mL) and separated by liquid-liquid extraction three times. The organic phase was taken, anhydrous magnesium sulfate was added, and after 30 min, filtration and rotary evaporation were carried out to finally obtain a white solid. The white solid was dissolved in dichloromethane / methanol (15 mL / 15 mL), dopamine hydrochloride (4.0 g) and triethylamine (2.0 mL) were added, and the reaction was carried out at 25 °C under a nitrogen atmosphere for 12 h. After the reaction was completed, the above solution was concentrated, then deionized water (100 mL) was added and allowed to stand for 2 h. After filtration, collection, and drying in vacuo, a brown solid was obtained. The brown solid was dissolved in methanol (20 mL), trifluoroacetic acid (1.7 g) was added, and the reaction was carried out at 25 °C under a nitrogen atmosphere for 12 h. All the solvent was removed by rotary evaporation and dried in a vacuum oven for 24 h to obtain pure DHHM; the yield was 50%.

[0061] Example 1:

[0062] According to Figure 1For the shown process flow, first dissolve 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 denoted as PEG1000) in 10 mL of N,N'-dimethylformamide (DMF). After adding 0.89 g of isophorone diisocyanate (IPDI) and 10 μL of dibutyltin dilaurate (DBTDL), react at 70 °C for 2 h to obtain a prepolymer solution system (this is step 1).

[0063] Then, in step 2, add 5 mL of a DMF solution containing 0.24 g of DDIMB and 0.11 g of DHHM to the above system, and continue to react at 70 °C for 20 h to obtain a polyurethane solution. After removing the solvent, soak it in water until equilibrium is reached, and the obtained injectable polyurethane material sample is denoted as DDIMB / DHHM / 1000_1 / 0.5.

[0064] The obtained injectable polyurethane material sample is in an elastic state in an environment with pH = 7, while in an acidic environment with pH = 3, it is in a viscous state and can be injected; that is, controllable injection is achieved through a pH-responsive secondary processing form.

[0065] Example 2:

[0066] According to Figure 2 , take 0.2 g of DDIMB / DHHM / 1000_1 / 0.5 and place it in a syringe equipped with a 20G flat needle. At this time, it is not injectable.

[0067] Then add 3 mL of acetic acid aqueous solution with pH = 3.0 to the syringe, acidolyze for 30 min, and then drain all the liquid. The acidolyzed DDIMB / DHHM / 1000_1 / 0.5 can be injected through the needle to the target position (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 form.

[0068] Figure 2 also shows the loss factor of the polyurethane material sample under some environments; use a rotational rheometer to test the loss factor. The rheometer is equipped with a stainless steel plate rotor with a diameter of 25 mm and a temperature-controlled quartz substrate. Place the sample on the substrate and move the rotor to a position 1.5 mm away from the substrate, and use a scraper to remove the extruded sample. Apply a strain of 1% in the frequency sweep test from 0.1 to 100 rad·s -1 to obtain the loss factor curve. Figure 2 In, the curves of different colors represent the loss factor curves of the acidolyzed polyurethane after being soaked in deionized water for different times. As the soaking time prolongs, the loss factor gradually decreases, indicating that the polyurethane gradually changes from a viscous state to an elastic state; it is confirmed that the polyurethane gradually recovers under the condition of pH = 7.

[0069] Figure 3 These are the in-situ NMR results of the DDIMB and DHHM mixture. First, DDIMB and DHHM were strictly mixed and dissolved in DMSO-d6 according to a molar ratio of 1 / 0.5. The corresponding ratio mixture of DDIMB and DHHM was used to equivalently replace DDIMB / DHHM / 1000_1 / 0.5, aiming to avoid the influence of other hydrogen atoms in the polyurethane on the judgment of chemical structure changes. After adding an aqueous acetic acid solution for acidolysis, it was found in the NMR of the mixture that the intensity of the corresponding peak of the active hydrogen on the carbon in the Schiff base decreased at 8.35 ppm, and the intensity of the characteristic peak of the hydrogen atoms on the benzene ring in DDIMB decreased. At the same time, a characteristic peak of the active hydrogen on the carbonyl carbon appeared at 10.1 ppm, accompanied by the appearance of a characteristic peak of the hydrogen atoms on the benzene ring shifting to a higher frequency. All of the above indicate that the Schiff base undergoes partial cleavage and forms benzaldehyde and amino groups. After the mixture was completely freeze-dried, DMSO-d6 was added again for dissolution and restoration. Finally, the active hydrogen on the carbonyl carbon disappeared, and the Schiff base was reformed. The NMR of the restored mixture was the same as that before acidolysis.

[0070] According to Figure 3 , during the acidolysis process, the chemical structure change of this crosslinked hydrophilic polyurethane from an elastic state to a viscous state was determined. The Schiff base structure of DDIMB will decompose into amino and aldehyde groups under acidic conditions and can be restored under neutral conditions.

[0071] Example 3:

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

[0073] And Figure 4 These are the shear modulus curves at different pH values and different times. The higher the pH value, the shorter the recovery time, that is, the so-called curing time is shorter; the present invention can achieve controllable injection.

[0074] Test using a rotational rheometer at 1% strain and 1 rad·s -1 to obtain Figure 4 . Among them, different pH values refer to the recovery at different pH values, that is, the acidolyzed polyurethane was immersed in deionized water with different pH values for testing. As the environmental pH increases, the recovery degree at the same time point improves. Therefore, the time and degree of re-crosslinking can be arbitrarily controlled by changing the pH during the recovery period.

[0075] Example 4:

[0076] Take 0.5 g of DDIMB / DHHM / 1000_1 / 0.5 and directly adhere it to the surfaces of various materials (without the acidolysis process, and the materials are used in the form of patches). See Figure 5 It has good adhesion to wood, glass, polypropylene, stainless steel, rubber, and animal tissues (heart, liver, stomach, lung, kidney), etc.

[0077] According to Figure 5 , this polyurethane has good adhesion effects on materials and animal organs of different materials. Moreover, it can follow the bending of the finger and has good compliance.

[0078] Quantitatively test the adhesion strength of the materials of different materials in Figure 5 . The test method is the lap joint test method as shown in Figure 6 (the obtained adhesion strength is the lap joint strength); the results are shown in Figure 6 , and the adhesion strengths are different.

[0079] Example 5:

[0080] According to the steps of Example 1, prepare the polyurethane material sample DDIMB / DHHM / 1000_1 / 0.25, with the difference that the molar ratio of DDIMB / DHHM is 1:0.25.

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

[0082] Conduct mechanical property tests on each sample. The results are shown in Figure 7 ; the obtained injectable material has good mechanical properties.

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

[0084] Example 6:

[0085] Take 0.2 g of DDIMB / DHHM / 1000_1 / 0.5 and put it into a syringe equipped with a 20G flat-angle needle. Add 3 mL of acetic acid aqueous solution with pH = 3.0 and acidolyze for 30 min. Then drain all the liquid, and inject the acidolyzed DDIMB / DHHM / 1000_1 / 0.5 into the bleeding site of the rat liver through the needle. Hemostasis is achieved within 1 min. The pH of the blood is about 7.4, which can provide a recovery environment, and at the same time, catechol will accelerate blood coagulation.

[0086] Make a 0.5-cm incision in the rat liver with a scalpel, inject polyurethane at the incision site, and take pictures at different times. The results are shown in Figure 8 . In the figure, the control group corresponds to making an incision without any further treatment; after injecting polyurethane at the incision site, hemostasis is achieved within 1 minute, while the control group without any treatment takes 5 minutes to stop bleeding.

[0087] Example 7:

[0088] Dissolve 2.0 g of polyethylene glycol (PEG2000) with a molecular weight of 2000 g / mol in 15 mL of dimethyl sulfoxide (DMSO). Add 0.51 g of hexamethylene diisocyanate (HDI) and 10 μL of DBTDL, and react at 70 °C for 2 h. Then, add 5 mL of a DMSO solution containing 0.20 g of DDIMB and 0.18 g of DHHM, and continue to react at 70 °C for 20 h to obtain a polyurethane solution. After removing the solvent, soak it in water until equilibrium is reached, and the sample is denoted as DDIMB / DHHM / 2000_1 / 1.

[0089] Example 8:

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

[0091] Example 9:

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

[0093] Inject the acidolyzed polyurethane (pH = 3) into the star-shaped area, and after recovery, complete filling of the area is achieved. The results are shown in Figure 9 ; indicating its potential to fill irregular parts and wounds. The polyurethane material of the present invention can fill irregular surfaces and can achieve filling and sealing after recovery.

[0094] Example 10:

[0095] Take 0.5 g of DDIMB / DHHM / 2000_1 / 1 and place it in a syringe equipped with a 20G flat-angle needle. Add 5 mL of acetic acid aqueous solution with pH = 3.0 and hydrolyze for 30 min. Then drain all the liquid. The hydrolyzed DDIMB / DHHM / 2000_1 / 1 is injected into the skin defect site of the rat through the needle, and slowly infiltrated and rinsed with 10 mL of normal saline. Then bandage the wound. After 9 days, the wound area is significantly lower than that of the experimental group rinsed only with normal saline.

[0096] Cut out a wound of about 1 cm on the rat epidermis, inject the hydrolyzed polyurethane into the wound, and use the normal saline group as a control. Take pictures of the wound recovery at different days and count the wound area. The results are shown in Figure 10 . The results show that the wound treated with this polyurethane has a faster recovery rate.

[0097] As can be seen from the above examples, from the aspects of injection materials and injection mechanism, the crosslinked hydrophilic polyurethane of the structure described in the present invention can utilize the pH-responsive ability of Schiff base to achieve controllable underwater injection through secondary processing. Moreover, it has good mechanical properties and can be used as adhesives, fillers or wound dressings, etc., and has broad application prospects.

[0098] The above examples are only used to illustrate the technical features and implementation process of the present invention, rather than limiting the technical solutions of the present invention. It should be pointed out that for those of ordinary skill in the art, the present invention can still be modified or equivalently replaced, and any modification or replacement that does not depart from the principle of the present invention is covered by the protection of the present invention.

Claims

1. An injectable polyurethane material, characterized in that: The injectable polyurethane material has a cross-linked polyurethane structure and hydrophilicity, and 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; 2. The injectable polyurethane material according to claim 1, characterized in that: The average molecular weight of the polyethylene glycol structure in the polyethylene glycol-diisocyanate prepolymer is 300-4000, and the diisocyanate structure is aliphatic.

3. The injectable polyurethane material according to claim 2, characterized in that: The average molecular weight of the polyethylene glycol structure in the polyethylene glycol-diisocyanate prepolymer is 600-2500, 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 to 3, characterized in that: The injectable polyurethane material is in a viscous state in an acidic aqueous solution and recovers to an elastic state in an injection environment with a pH value of ≥7.

5. The method for preparing an injectable polyurethane material according to any one of claims 1 to 4, characterized in that: include: The diisocyanate and polyethylene glycol are reacted in a solvent to obtain a polyethylene glycol-diisocyanate prepolymer; then a cross-linking agent having a structure of Formula 1 and a chain extender having a structure of Formula 2 are added to carry out polymerization, and after the polymerization is completed, the solvent is removed to obtain the injectable polyurethane material; 6. The preparation method according to claim 5, characterized in that: The reaction of the diisocyanate and the polyethylene glycol is carried out in the presence of an organic tin catalyst, which is dibutyltin dilaurate or dioctyltin diisooctanoate; the solvent is N,N'-dimethylformamide or dimethyl sulfoxide; the temperature of the reaction of the diisocyanate and the polyethylene glycol is 60-80°C and the time is 1-3 hours.

7. The preparation method according to claim 6, characterized in that: The mass ratio of the cross-linking agent to the polyethylene glycol is 0.1-0.15:1, and the mass ratio of the chain extender to the polyethylene glycol is 0.05-0.1:

1.

8. The preparation method according to claim 7, characterized in that: The polymerization temperature is 60-80° C. and the polymerization time is 15-30 hours. After removing the solvent, the mixture is immersed in water for equilibrium to obtain the product.

9. Use of the injectable polyurethane material according to any one of claims 1 to 4 as an adhesive, filler or wound dressing.

10. The use according to claim 9, characterized in that: The injectable polyurethane material is injected underwater in a pH-responsive manner.

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