Hydrogel testicular prosthesis based on zwitterionic polymer and preparation method of hydrogel testicular prosthesis

Abstract

The invention relates to the technical field of medical biological materials, in particular to a hydrogel testicular prosthesis based on a zwitterionic polymer and a preparation method of the hydrogel testicular prosthesis. The hydrogel testicular prosthesis based on the zwitterionic polymer is prepared from a raw material system comprising a zwitterionic monomer, N-acryloyl urea amine and N-acryloyl glycinamide. The hydrogel testicular prosthesis based on the zwitterionic polymer has excellent stability and mechanical properties, can meet actual application requirements, and can be applied to the fields of veterinary medicine and the like.

Description

Technical Field

[0001] The present invention relates to the technical field of medical biomaterials, and in particular to a hydrogel testicular prosthesis based on zwitterionic polymers and a preparation method thereof. Background Art

[0002] In modern veterinary medicine, castration or neutering of male animals involves removing their testicles to cut off gonadal hormone production and prevent testicular diseases such as orchitis, testicular torsion, and testicular tumors. However, orchiectomy not only results in the loss of a male animal's physical organs but also creates psychological deficiencies. Testicular prostheses can, to some extent, compensate for these physical and psychological deficiencies in orchiectomized males.

[0003] A testicular prosthesis is a device that can be implanted in the scrotum of a male animal and resembles a testicle. Currently, most testicular prostheses on the market are made of silicone rubber. While these materials can meet certain aesthetic and tactile requirements, the helical nature of the silicone rubber molecules in silicone rubber results in very low polarity and strong hydrophobicity. This results in poor affinity with tissues, making them prone to adverse reactions after implantation and resulting in poor biocompatibility.

[0004] As an emerging biomaterial, hydrogels exhibit good biocompatibility due to their high water content, softness, and structure similar to biological tissue. Therefore, hydrogels are considered potential candidates to replace silicone rubber. However, due to their high water content, hydrogels may swell, leak, or degrade after prolonged implantation, resulting in insufficient stability.

[0005] Therefore, developing a testicular prosthesis for animals with excellent stability is an urgent problem to be solved in this field. Summary of the Invention

[0006] The present invention provides a zwitterionic polymer-based hydrogel testicular prosthesis, which is prepared from a raw material system including zwitterionic monomers, N-acryloylureaamine and N-acryloylglycineamide, and has excellent stability and mechanical properties.

[0007] The present invention also provides a method for preparing a zwitterionic polymer-based hydrogel testicular prosthesis, by which the zwitterionic polymer-based hydrogel testicular prosthesis having excellent stability and mechanical properties can be prepared.

[0008] The first aspect of the present application provides a zwitterionic polymer-based hydrogel testis prosthesis prepared from a raw material system comprising a zwitterionic monomer, N-acryloyl urea amine and N-acryloyl glycine amide, the zwitterionic monomer being any one of compounds shown in formula (1), formula (2), formula (3), formula (4), formula (5), formula (6): Formula (1), Formula (2), Formula (3), Formula (4), Formula (5), Formula (6); The chemical structural formula of the N-acryloyl urea amine is shown in formula (7): Formula (7); The chemical structural formula of the N-acryloyl glycine amide is shown in formula (8): Formula (8).

[0009] The zwitterionic polymer-based hydrogel testis prosthesis as described above, in the raw material system, the mass ratio of the N-acryloyl urea amine, the N-acryloyl glycine amide and the zwitterionic monomer is (1-3):(1-3):(0.1-2).

[0010] The second aspect of the present application provides a preparation method of the zwitterionic polymer-based hydrogel testis prosthesis, comprising the following steps: The zwitterionic monomer, N-acryloyl urea amine and N-acryloyl glycine amide are dissolved in a mixed solvent, a photoinitiator is added and stirring treatment is performed, to obtain a mixed solution; The mixed solution is poured into a mold, irradiation is performed under light, and then demolding is performed, to obtain a colloid; The colloid is soaked in a buffer solution and reaches swelling equilibrium, to obtain the zwitterionic polymer-based hydrogel testis prosthesis.

[0011] The preparation method of the zwitterionic polymer-based hydrogel testis prosthesis as described above, the mass ratio of the N-acryloyl urea amine, the N-acryloyl glycine amide and the zwitterionic monomer is (1-3):(1-3):(0.1-2).

[0012] In the above-mentioned method for preparing a hydrogel testicular prosthesis based on zwitterionic polymers, the amount of the photoinitiator in the mixed solution is 1% to 5% of the total amount of N-acryloylureaamine, N-acryloylglycineamide and zwitterionic monomers.

[0013] In the above-mentioned method for preparing a hydrogel testicular prosthesis based on a zwitterionic polymer, the photoinitiator is at least one of 2-hydroxy-2-methyl-1-phenyl-1-propanone, 2-hydroxy-4′-(2-hydroxyethoxy)-2-methylpropiophenone, and lithium phenyl (2,4,6-trimethylbenzoyl) phosphate.

[0014] In the above-mentioned method for preparing a hydrogel testicular prosthesis based on zwitterionic polymers, in the mixed solution, the ratio of the total mass of N-acryloylureaamine, N-acryloylglycineamide and zwitterionic monomer to the mass of the mixed solvent is 0.3 to 1.5.

[0015] In the above-mentioned method for preparing the hydrogel testicular prosthesis based on zwitterionic polymers, the mixed solvent is formed by mixing the following components by volume: 60% to 80% deionized water and 20% to 40% dimethyl sulfoxide.

[0016] In the above-mentioned method for preparing a hydrogel testicular prosthesis based on zwitterionic polymers, the light is ultraviolet light with a wavelength of 100nm to 400nm or blue light with a wavelength of 400nm to 500nm, and the irradiation time is 600s to 3600s.

[0017] In the above-mentioned method for preparing the hydrogel testicular prosthesis based on zwitterionic polymer, the soaking time is 48 hours to 120 hours and the temperature is 20° C. to 40° C.

[0018] The beneficial technical effects of the present invention include at least: The zwitterionic polymer-based hydrogel testicular prosthesis provided by the present invention is prepared from a raw material system including zwitterionic monomers, N-acryloylureaamine, and N-acryloylglycineamide. The zwitterionic polymer-based hydrogel testicular prosthesis has excellent stability and mechanical properties. First, compared with testicular prostheses made of traditional silicone rubber materials, the zwitterionic polymer-based hydrogel testicular prosthesis provided by the present invention has good biocompatibility, which helps improve the affinity of the zwitterionic polymer-based hydrogel testicular prosthesis with body tissues and reduce adverse reactions after implantation. Second, the zwitterionic polymer-based hydrogel testicular prosthesis has excellent stability, which helps improve the long-term effect and safety of the zwitterionic polymer-based hydrogel testicular prosthesis and reduces the frequency of replacement or repair. Third, the zwitterionic polymer-based hydrogel testicular prosthesis has excellent mechanical properties (0.19-0.32 MPa), which match the modulus of natural testicles, can effectively withstand external pressure and impact, and avoid deformation or damage of the prosthesis after implantation. BRIEF DESCRIPTION OF THE DRAWINGS

[0019] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the following briefly introduces the drawings required for use in the embodiments or the description of the prior art. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying any creative work.

[0020] Figure 1 is the H NMR spectrum of N-acryloylureaamine (NASC) in the present invention; Figure 2 is the H NMR spectrum of N-acryloylglycinamide (NAGA) in the present invention; Figure 3 is the H NMR spectrum of 2-((2-hydroxy-3-(methacryloyloxy)propyl)dimethylamino)acetate (CB-OH) in the present invention; Figure 4 This is an appearance diagram of the zwitterionic polymer-based hydrogel testicular prosthesis in Example 1 of the present invention; Figure 5 Schematic diagram of the molecular chain of the zwitterionic polymer-based hydrogel testicular prosthesis in Example 1 of the present invention; Figure 6 : is the swelling curve of the zwitterionic polymer-based hydrogel testicular prosthesis in Example 1 of the present invention; Figure 7 : is the swelling curve of the zwitterionic polymer-based hydrogel testicular prosthesis in Example 2 of the present invention; Figure 8: is the swelling curve of the zwitterionic polymer-based hydrogel testicular prosthesis in Example 3 of the present invention; Figure 9 : is the swelling curve of the zwitterionic polymer-based hydrogel testicular prosthesis in Example 4 of the present invention; Figure 10 : is the swelling curve of the zwitterionic polymer-based hydrogel testicular prosthesis in Example 5 of the present invention; Figure 11 : is the swelling curve of the zwitterionic polymer-based hydrogel testicular prosthesis in Example 6 of the present invention; Figure 12 : is the swelling curve of the zwitterionic polymer-based hydrogel testicular prosthesis in Example 7 of the present invention; Figure 13 : is the swelling curve of the zwitterionic polymer-based hydrogel testicular prosthesis in Example 8 of the present invention; Figure 14 This is the swelling curve of the zwitterionic polymer-based hydrogel testicular prosthesis in Comparative Example 1 of the present invention; Figure 15 This is the swelling curve of the zwitterionic polymer-based hydrogel testicular prosthesis in Comparative Example 2 of the present invention; Figure 16 This is the swelling curve of the zwitterionic polymer-based hydrogel testicular prosthesis in Comparative Example 3 of the present invention. DETAILED DESCRIPTION

[0021] To make the objectives, technical solutions, and advantages of the present invention more clear, the technical solutions in the embodiments of the present invention will be clearly and completely described below in conjunction with the embodiments of the present invention. Obviously, the described embodiments are part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making creative efforts shall fall within the scope of protection of the present invention.

[0022] Unless otherwise specified, the raw materials and reagents used in the following examples can be obtained from commercial sources; the processes used, unless otherwise specified, are conventional processes in the art.

[0023] The first aspect of the present invention provides a hydrogel testicular prosthesis based on a zwitterionic polymer, which is prepared from a raw material system including a zwitterionic monomer, N-acryloylureaamine and N-acryloylglycinamide, wherein the zwitterionic monomer is any one of the compounds represented by formula (1), formula (2), formula (3), formula (4), formula (5) and formula (6): Formula (1) Formula (2) Formula (3) Formula (4) Formula (5) Formula (6); The chemical structure of the N-acryloylureaamine is shown in formula (7): Formula (7); The chemical structure of the N-acryloylglycine amide is shown in formula (8): Formula (8).

[0024] In the present invention, the zwitterionic monomer refers to a monomer having both positive and negative charges.

[0025] The present invention facilitates the preparation of a hydrogel testicular prosthesis based on a zwitterionic polymer with excellent stability and mechanical properties by subjecting a raw material system including the zwitterionic monomer, N-acryloylureaamine and N-acryloylglycinamide to a polymerization reaction.

[0026] In a specific embodiment, in the above raw material system, the mass ratio of N-acryloylureaamine, N-acryloylglycineamide and zwitterionic monomer is (1-3): (1-3): (0.1-2), for example, the mass ratio of N-acryloylureaamine, N-acryloylglycineamide and zwitterionic monomer is 1:1:0.1, 1:1:1, 1:1:1.5, 1:1:2, 2:2:1, 2:2:0.1, etc.

[0027] When the mass ratio of N-acryloylureaamine, N-acryloylglycineamide, and zwitterionic monomer in the above-mentioned raw material system is within the above-mentioned range, the zwitterionic monomer can undergo a polymerization reaction with N-acryloylureaamine and N-acryloylglycineamide, thereby facilitating the preparation of a hydrogel testicular prosthesis based on a zwitterionic polymer.

[0028] Furthermore, in the above raw material system, the mass ratio of N-acryloylureaamine, N-acryloylglycineamide and zwitterionic monomer may be preferably 2:2:1.

[0029] When the mass ratio of N-acryloylureaamine, N-acryloylglycineamide and zwitterionic monomer in the above-mentioned raw material system is 2:2:1, N-acryloylureaamine, N-acryloylglycineamide and zwitterionic monomer can be fully polymerized, which is conducive to the preparation of a hydrogel testicular prosthesis based on zwitterionic polymer with excellent stability and mechanical properties.

[0030] A second aspect of the present invention provides a method for preparing the above-mentioned zwitterionic polymer-based hydrogel testicular prosthesis, comprising the following steps: Dissolving a zwitterionic monomer, N-acryloylureaamine and N-acryloylglycinamide in a mixed solvent, adding a photoinitiator and stirring to obtain a mixed solution; The mixed liquid is poured into a mold, irradiated under light, and then demoulded to obtain a colloid; The colloid is immersed in a buffer solution and reaches swelling equilibrium to obtain a hydrogel testicular prosthesis based on zwitterionic polymer.

[0031] The present invention does not impose any particular limitation on the specific material of the mold, and the mold can be selected according to actual needs. In some embodiments, the mold can be a polydimethylsiloxane mold.

[0032] The present invention does not particularly limit the specific sources of the raw materials and reagents used to prepare the hydrogel testicular prosthesis based on zwitterionic polymers. They can be purchased through commercial channels or prepared by methods known in the art.

[0033] The present invention does not impose any particular limitation on the specific amount of the buffer solution, which can be selected according to actual needs.

[0034] Specifically, the present invention first dissolves N-acryloylureaamine, N-acryloylglycineamide and zwitterionic monomers in a mixed solvent to obtain a mixed solution, then adds a photoinitiator to the mixed solution and stirs it to obtain a second mixed solution. The function of the photoinitiator is to initiate a polymerization reaction during the subsequent irradiation under light, and the stirring is to fully dissolve the photoinitiator in the mixed solution and obtain a uniformly mixed second mixed solution; the stirred second mixed solution is poured into a mold, and then the mixed solution is irradiated under light to induce a polymerization reaction of N-acryloylureaamine, N-acryloylglycineamide and zwitterionic monomers. After the polymerization reaction is completed, a colloidal substance is obtained, and the colloidal substance is removed from the mold, i.e., demolded, to obtain a colloid; the colloid is immersed in a buffer solution. The colloid absorbs water and expands due to the immersion, and finally reaches a swelling equilibrium, thereby obtaining a hydrogel testicular prosthesis based on zwitterionic polymers with excellent stability and mechanical properties.

[0035] The principle of the present invention is explained as follows: N-acryloylureaamine, N-acryloylglycineamide and zwitterionic monomers all contain a carbon-carbon double bond (C=C) in their structures. N-acryloylureaamine, N-acryloylglycineamide and zwitterionic monomers can undergo free radical polymerization to form polymer molecular chains, which are then cross-linked by hydrogen bonds to form a three-dimensional network structure, thereby forming a hydrogel.

[0036] The process of the above-mentioned polymerization reaction is as follows: the photoinitiator generates active free radicals after being exposed to light. The active free radicals attack the carbon-carbon double bond (C=C) of the double-bond monomer (N-acryloylureaamine, N-acryloylglycineamide and zwitterionic monomer), breaking the π bond to form monomer free radicals. The monomer free radicals react with new monomer molecules (N-acryloylureaamine, N-acryloylglycineamide and zwitterionic monomers) to form longer chain free radicals through the breaking of the double bond.

[0037] In a specific embodiment, the mass ratio of the N-acryloylureaamine, the N-acryloylglycineamide and the zwitterionic monomer is (1-3): (1-3): (0.1-2), and preferably 2:2:1.

[0038] When the mass ratio of N-acryloylureaamine, N-acryloylglycineamide and zwitterionic monomer is within the above range, the zwitterionic monomer can undergo polymerization reaction with N-acryloylureaamine and N-acryloylglycineamide, thereby facilitating the preparation of a hydrogel testicular prosthesis based on zwitterionic polymer.

[0039] In a specific embodiment, in the mixed solution, the amount of the photoinitiator is 1% to 5% of the total amount of N-acryloylureaamine, N-acryloylglycineamide and zwitterionic monomer.

[0040] When the amount of the photoinitiator in the mixed liquid is the parameter of the total amount of N-acryloylureaamine, N-acryloylglycineamide and zwitterionic monomer within the above range, the N-acryloylureaamine, N-acryloylglycineamide, zwitterionic monomer and photoinitiator in the second mixed liquid can be better matched, so that the polymerization reaction can proceed more fully, thereby facilitating the preparation of a hydrogel testicular prosthesis based on zwitterionic polymers with excellent stability and mechanical properties.

[0041] In a specific embodiment, the photoinitiator is at least one of 2-hydroxy-2-methyl-1-phenyl-1-propanone, 2-hydroxy-4′-(2-hydroxyethoxy)-2-methylpropiophenone, and phenyl (2,4,6-trimethylbenzoyl) lithium phosphate, preferably 2-hydroxy-2-methyl-1-phenyl-1-propanone.

[0042] When the above substances are selected as photoinitiators, they can promote the polymerization reaction between N-acryloylureaamine, N-acryloylglycineamide and zwitterionic monomers in the mixed solution, which is beneficial to the subsequent preparation of a hydrogel testicular prosthesis based on zwitterionic polymers with excellent stability and mechanical properties.

[0043] In a specific embodiment, in the mixed solution, the ratio of the total mass of N-acryloylureaamine, N-acryloylglycineamide and zwitterionic monomer to the mass of the mixed solvent is 0.3 to 1.5.

[0044] The mixed solvent is prepared by mixing the following components by volume percentage: 60% to 80% deionized water and 20% to 40% dimethyl sulfoxide, preferably 70% deionized water and 30% dimethyl sulfoxide.

[0045] When the parameter of the ratio of the total mass of N-acryloylureaamine, N-acryloylglycineamide, and zwitterionic monomer to the mass of the mixed solvent in the above-mentioned mixed liquid is within the above-mentioned range, and when the mixed solvent composed of the above-mentioned deionized water and dimethyl sulfoxide is selected, the solubility of N-acryloylureaamine, N-acryloylglycineamide, and zwitterionic monomer in the mixed solvent can be controlled, thereby preparing hydrogel testicular prostheses based on zwitterionic polymers with different mechanical properties.

[0046] In a specific embodiment, the light is ultraviolet light with a wavelength of 100 nm to 400 nm or blue light with a wavelength of 400 nm to 500 nm, and the irradiation time is 600 s to 3600 s.

[0047] When the parameters of the above-mentioned light are selected for irradiation and the irradiation time are within the above-mentioned range, the photoinitiator can be effectively excited to generate free radicals, thereby initiating a sufficient polymerization reaction between N-acryloylureaamine, N-acryloylglycineamide and zwitterionic monomers, which is conducive to the preparation of a hydrogel testicular prosthesis based on zwitterionic polymers.

[0048] In a specific embodiment, the soaking time is 48 hours to 120 hours and the temperature is 20 to 40°C.

[0049] When the parameters of immersion time and temperature are within the above ranges, the colloid is allowed to fully absorb water and reach swelling equilibrium, thereby obtaining a zwitterionic polymer-based hydrogel testicular prosthesis with excellent stability and mechanical properties.

[0050] In one embodiment, the buffer solution comprises a phosphate buffer solution.

[0051] The present invention is further described below through specific examples.

[0052] The carboxybetaine urea acrylate (CBUIA) used in the following examples was synthesized according to the method for synthesizing CBUIA in the reference (Lowhysteresis zwitterionic supramolecular polymer ion-conductive elastomers with anti-freezing properties, high stretchability, and self-adhesion for flexible electronic devices, Materials Horizons, 6, 33-36 (2023)); carboxybetaine urethane acrylate (CBUTA) was synthesized according to the method for synthesizing CBUTA in the reference (An Injectable Self-Crosslinked Wholly Supramolecular Polyzwitterionic Hydrogel for Regulating Microenvironment to Boost Infected Diabetic Wound Healing, Advanced Functional Materials, 11, 2628-2642 (2024)).

[0053] Preparation of N-acryloylureaamine (NASC): 12.7 g of ureaamine hydrochloride, 12 mL of deionized water and 67.2 mL of potassium carbonate solution (2 mol / L) were added to a round-bottom flask in sequence under ice bath conditions, and then 36 mL of ice ether was added to obtain a mixture solution; 11.4 g of acryloyl chloride was dissolved in 48 mL of ether to obtain an ether solution containing acryloyl chloride, and then the ether solution containing acryloyl chloride was slowly dripped into the above mixture solution, and the mixture solution was stirred with a magnetic stirrer during the dripping process and the whole process was kept in an ice bath environment; after the ether solution containing acryloyl chloride was added, a mixed solution was obtained; the mixed solution was placed under ice bath conditions The mixture was stirred for 4 hours, during which a large amount of white precipitate was produced. After the reaction, the mixture was filtered to remove the solvent and retain the white precipitate. The white precipitate was then washed by centrifugation with cold water, the supernatant was removed, and the lower precipitate was retained to obtain a crude product. The crude product was transferred to a round-bottom flask, deionized water was added, and the mixture was heated at 95°C for 3 hours, followed by centrifugation. The supernatant after centrifugation was transferred to a freeze-drying box, cooled to room temperature, and then transferred to a -50°C refrigerator for freezing. Finally, the mixture was freeze-dried to obtain a white pure product, N-acryloylureaamine (NASC). The nuclear magnetic hydrogen spectrum of NASC is shown in FIG. Figure 1As shown, the chemical structure of NASC is as follows:

[0054] Preparation of N-acryloylglycinamide (NAGA): Weigh 6.30 g of glycineamide hydrochloride powder into a 250 mL single-necked round-bottom flask. Then, place the single-necked round-bottom flask in an ice-water bath. Measure 6 mL of deionized water, 33.6 mL of a 2 mol / L potassium carbonate aqueous solution, and 18 mL of anhydrous ether and add them to the single-necked round-bottom flask in sequence. Stir in an ice-water bath until the glycineamide hydrochloride powder is completely dissolved. 24 mL of anhydrous ether was added to a 50 mL constant pressure dropping funnel, and 5.7 mL of acryloyl chloride was added to obtain diluted acryloyl chloride. Under stirring in an ice-water bath, the knob of the constant pressure dropping funnel was adjusted to slowly dropwise add the diluted acryloyl chloride to the round-bottom flask. After the addition was complete, the ice-water bath was maintained and the stirring reaction was continued for 4 h to obtain a reaction solution. The reaction solution was adjusted to pH 2 with a 2 mol / L dilute hydrochloric acid solution, and the reaction solution was repeatedly extracted three times with 50 mL of anhydrous ether, retaining the aqueous phase to remove the organic phase (anhydrous ether) and organic impurities (such as acrylate) in the reaction solution, thereby obtaining an extracted aqueous phase; The aqueous reaction solution after extraction was adjusted to pH = 7 with a 2 mol / L NaOH solution, frozen in an ultra-low temperature refrigerator, and freeze-dried to obtain a crude product (white powder) containing inorganic salts (such as NaCl, KCl, etc.); the crude product was added to 200 mL of a mixed solvent (anhydrous ethanol and anhydrous methanol were prepared in a volume ratio of 4:1) and vigorously stirred to fully disperse the crude product in the mixed solvent to obtain a mixture; thereafter, the insoluble matter in the mixture was removed by suction filtration to obtain a filtrate, and the filtrate was subjected to rotary evaporation at 35°C to obtain a concentrate, which was then placed in a -20°C refrigerator for recrystallization for 20 minutes and then suction filtered to obtain a white product; The white product was vacuum dried to obtain purified N-acryloylglycineamide (NAGA). The H NMR spectrum of NAGA is as follows: Figure 2 As shown, the chemical structure of NAGA is as follows:

[0055] Preparation of 2-((2-hydroxy-3-(methacryloyloxy)propyl)dimethylamino)acetate (CB-OH): 9.37 g of sarcosine tert-butyl ester hydrochloride was dissolved in 60 mL of water and neutralized with 5 g of sodium bicarbonate to obtain sarcosine tert-butyl ester; the sarcosine tert-butyl ester was extracted with 60 mL of dichloromethane, and the solvent was evaporated to obtain 7.4 g of purified sarcosine tert-butyl ester; 7.4 g of purified sarcosine tert-butyl ester, 10.39 mL of glycidyl methacrylate, 0.4 g of magnesium sulfate, and 20 mL of dichloromethane were reacted at 60° C. under nitrogen protection for 60 hours to obtain a reaction product; the reaction product was filtered to remove insoluble magnesium sulfate to obtain a filtrate; the filtrate was mixed with 140 mL of iodomethane (the volume ratio of iodomethane to filtrate was 4: 1) A methylation reaction is performed to form white CB-OH-tBu crystals; the CB-OH-tBu crystals are washed with ether and vacuum dried, then dissolved in trifluoroacetic acid (TFA) for 2 hours to completely deprotect the tBu group to obtain a product, which is precipitated in ether and dissolved in water, and stirred with an ion exchange resin at 0°C for 30 minutes to obtain a filtrate containing CB-OH; finally, the filtrate containing CB-OH is washed three times with dichloromethane and lyophilized to obtain a white powder, namely 2-((2-hydroxy-3-(methacryloyloxy)propyl)dimethylamino)acetate (CB-OH). The H NMR spectrum of CB-OH is as follows: Figure 3 As shown, the chemical structure of CB-OH is as follows:

[0056] Example 1 The method for preparing a hydrogel testicular prosthesis based on a zwitterionic polymer provided in this embodiment includes the following steps: (1) 2 g of N-acryloylureaamine (NASC), 2 g of N-acryloylglycinamide (NAGA) and 1 g of 2-((2-hydroxy-3-(methacryloyloxy)propyl)dimethylamino)acetate (CB-OH) were dissolved in 10 g of a mixed solvent (the mixed solvent was a mixture of 70% deionized water and 30% dimethyl sulfoxide by volume), and then 23.5 μL of 2-hydroxy-2-methyl-1-phenyl-1-propanone (CAS No.: 7473-98-5) was added and stirred thoroughly to obtain a uniform mixed solution.

[0057] (2) The mixed liquid was poured into a polydimethylsiloxane mold, irradiated under ultraviolet light with a wavelength of 310 nm for 3600 s, and then demolded to obtain a colloid.

[0058] (3) Soak the colloid in a phosphate buffer solution at 37°C for 72 hours until it reaches swelling equilibrium. Figure 4 The hydrogel testicular prosthesis based on zwitterionic polymers is shown in FIG. Figure 5 shown.

[0059] Example 2 The preparation method of the hydrogel testicular prosthesis based on zwitterionic polymer provided in this embodiment is basically the same as that in Example 1, except that: (1) 1 g of 2-((2-hydroxy-3-(methacryloyloxy)propyl)dimethylamino)acetate (CB-OH) was replaced with 0.1 g of 2-((2-hydroxy-3-(methacryloyloxy)propyl)dimethylamino)acetate (CB-OH).

[0060] Example 3 The preparation method of the hydrogel testicular prosthesis based on zwitterionic polymer provided in this embodiment is basically the same as that in Example 1, except that: (1) 1 g of 2-((2-hydroxy-3-(methacryloyloxy)propyl)dimethylamino)acetate (CB-OH) was replaced with 2 g of 2-((2-hydroxy-3-(methacryloyloxy)propyl)dimethylamino)acetate (CB-OH).

[0061] Example 4 The preparation method of the hydrogel testicular prosthesis based on zwitterionic polymer provided in this embodiment is basically the same as that in Example 1, except that: 2-((2-hydroxy-3-(methacryloyloxy)propyl)dimethylamino)acetate (CB-OH) was replaced with carboxybetaine urea acrylate (CBUIA). The chemical structure of CBUIA is as follows:

[0062] Example 5 The preparation method of the hydrogel testicular prosthesis based on zwitterionic polymer provided in this embodiment is basically the same as that in Example 1, except that: 2-((2-hydroxy-3-(methacryloyloxy)propyl)dimethylamino)acetate (CB-OH) was replaced with carboxybetaine urethane acrylate (CBUTA). The chemical structure of CBUTA is as follows:

[0063] Example 6 The preparation method of the hydrogel testicular prosthesis based on zwitterionic polymer provided in this embodiment is basically the same as that in Example 1, except that: Replace 2-((2-hydroxy-3-(methacryloyloxy)propyl)dimethylamino)acetate (CB-OH) with carboxybetaine acrylamide (CBAA). The chemical structure of CBAA is as follows:

[0064] Example 7 The preparation method of the hydrogel testicular prosthesis based on zwitterionic polymer provided in this embodiment is basically the same as that in Example 1, except that: 2-((2-hydroxy-3-(methacryloyloxy)propyl)dimethylamino)acetate (CB-OH) was replaced with 2-methacryloyloxyethylphosphorylcholine (MPC). The chemical structure of MPC is as follows:

[0065] Example 8 The preparation method of the hydrogel testicular prosthesis based on zwitterionic polymer provided in this embodiment is basically the same as that in Example 1, except that: Replace 2-((2-hydroxy-3-(methacryloyloxy)propyl)dimethylamino)acetate (CB-OH) with carboxylic acid betaine (CBMA). The chemical structure of CBMA is as follows:

[0066] Comparative Example 1 The preparation method of the hydrogel testicular prosthesis based on zwitterionic polymer provided in this comparative example includes the following steps: (1) 2 g of N-acryloylureaamine (NASC), 2 g of N-acryloylglycinamide (NAGA) and 1 g of 2-((2-hydroxy-3-(methacryloyloxy)propyl)dimethylamino)acetate (CB-OH) were dissolved in 10 g of a mixed solvent (the mixed solvent was a mixture of 70% deionized water and 30% dimethyl sulfoxide by volume), and then 27.8 μL of 2-hydroxy-4′-(2-hydroxyethoxy)-2-methylpropiophenone (CAS No.: 106797-53-9) was added and stirred thoroughly to obtain a uniform mixture.

[0067] (2) The mixed liquid was poured into a polydimethylsiloxane mold, irradiated under ultraviolet light with a wavelength of 310 nm for 3600 s, and then demolded to obtain a colloid.

[0068] (3) The colloid was immersed in a phosphate buffer solution at a temperature of 37°C for 72 hours. After the swelling equilibrium was reached, a hydrogel testicular prosthesis based on zwitterionic polymer was obtained.

[0069] Comparative Example 2 The preparation method of the hydrogel testicular prosthesis based on zwitterionic polymer provided in this comparative example includes the following steps: (1) 2 g of N-acryloylureaamine (NASC), 2 g of N-acryloylglycinamide (NAGA) and 1 g of 2-((2-hydroxy-3-(methacryloyloxy)propyl)dimethylamino)acetate (CB-OH) were dissolved in 10 g of a mixed solvent (the mixed solvent was a mixture of 70% deionized water and 30% dimethyl sulfoxide by volume), and then 0.5 g of phenyl (2,4,6-trimethylbenzoyl) lithium phosphate (CAS No.: 85073-19-4) was added and stirred thoroughly to obtain a uniform mixed solution.

[0070] (2) The mixed liquid was poured into a polydimethylsiloxane mold, irradiated under ultraviolet light with a wavelength of 310 nm for 3600 s, and then demolded to obtain a colloid.

[0071] (3) The colloid was immersed in a phosphate buffer solution at a temperature of 37°C for 72 hours. After the swelling equilibrium was reached, a hydrogel testicular prosthesis based on zwitterionic polymer was obtained.

[0072] Comparative Example 3 (without addition of N-acryloylglycinamide and N-acryloylureaamine) The preparation method of the hydrogel testicular prosthesis based on zwitterionic polymer provided in this embodiment is basically the same as that in Example 1, except that: (1) Dissolve 1 g of 2-((2-hydroxy-3-(methacryloyloxy)propyl)dimethylamino)acetate (CB-OH) in 5 g of pure water, then add 23.5 μL of 2-hydroxy-2-methyl-1-phenyl-1-propanone (CAS No.: 7473-98-5) and stir thoroughly to obtain a uniform mixture.

[0073] Comparative Example 4 (without adding N-acryloylglycineamide) The preparation method of the hydrogel testicular prosthesis based on zwitterionic polymer provided in this comparative example is basically the same as that in Example 1, except that: (1) 2 g of N-acryloylureaamine (NASC) and 1 g of 2-((2-hydroxy-3-(methacryloyloxy)propyl)dimethylamino)acetate (CB-OH) were dissolved in 10 g of a mixed solvent (the mixed solvent was a mixture of 70% deionized water and 30% dimethyl sulfoxide by volume), and then 23.5 μL of 2-hydroxy-2-methyl-1-phenyl-1-propanone (CAS No.: 7473-98-5) was added and stirred thoroughly to obtain a uniform mixed solution.

[0074] During the preparation of the hydrogel testicular prosthesis based on zwitterionic polymer in this comparative example, the inventors found that the uniform mixed solution in this comparative example could not form a gel, and therefore no subsequent performance test was performed.

[0075] Comparative Example 5 (without adding N-acryloyl urea amine) The preparation method of the zwitterionic polymer-based hydrogel testis prosthesis provided in the present comparative example is basically the same as that in Example 1, except that: (1) 2 g of N-acryloylglycine amide (NAGA) and 1 g of 2-((2-hydroxy-3- (methacryloyloxy) propyl) dimethylamino) acetate (CB-OH) were dissolved in 10 g of a mixed solvent (the mixed solvent was mixed by 70% deionized water and 30% dimethyl sulfoxide by volume percentage), then 23.5 μL of 2-hydroxy-2-methyl-1-phenyl-1-propanone (CAS No.: 7473-98-5) was added and subjected to thorough stirring treatment to obtain a uniform mixture.

[0076] During the preparation of the zwitterionic polymer-based hydrogel testis prosthesis in the present comparative example, the inventors found that the uniform mixture in the present comparative example could not be gelled, so no subsequent performance test was performed.

[0077] Comparative Example 6 The preparation method of the zwitterionic polymer-based hydrogel testis prosthesis provided in the present comparative example is basically the same as that in Example 1, except that: (1) 2 g of N-acryloylglycine amide (NAGA) and 1 g of 2-((2-hydroxy-3- (methacryloyloxy) propyl) dimethylamino) acetate (CB-OH) were dissolved in 10 g of a mixed solvent (the mixed solvent was mixed by 70% deionized water and 30% dimethyl sulfoxide by volume percentage), then 23.5 μL of 2-hydroxy-2-methyl-1-phenyl-1-propanone (CAS No.: 7473-98-5) was added and subjected to thorough stirring treatment to obtain a uniform mixture.

[0078] During the preparation of the zwitterionic polymer-based hydrogel testis prosthesis in the present comparative example, the inventors found that the uniform mixture in the present comparative example could not be gelled, so no subsequent performance test was performed.

[0079] Performance test 1. Mechanical properties The zwitterionic polymer-based hydrogel testis prostheses in Examples 1-8 and Comparative Examples 1-3 of the present application were subjected to the following tests, and the test results are shown in Tables 1 and 2. Strength (MPa): The test method was in accordance with the national standard GB / T 528-2009.

[0080] Table 1 Test results

[0081] Table 2 Test results

[0082] As can be seen from Tables 1 and 2, the zwitterionic polymer-based hydrogel testicular prosthesis provided in the embodiments of the present invention has excellent mechanical properties (strength can reach 0.32 MPa).

[0083] 2. Stability The zwitterionic polymer-based hydrogel testicular prostheses of Examples 1-8 of the present invention and Comparative Examples 1-3 were subjected to stability tests. The specific method was as follows: 1 gram (g) of the zwitterionic polymer-based hydrogel testicular prostheses was immersed in PBS buffer, and the time-mass swelling curve was recorded and the swelling ratio was calculated (the calculation results are shown in Tables 3 and 4) to evaluate the stability of the zwitterionic polymer-based hydrogel testicular prostheses. Swelling ratio = swelling equilibrium mass / initial mass.

[0084] Table 3 Swelling ratio

[0085] Table 4 Swelling ratio

[0086] The lower the swelling ratio, the better the stability of the material. Figure 6-Figure 16 As shown in Tables 3 and 4, the zwitterionic polymer-based hydrogel testicular prostheses provided in Examples 1-8 and Comparative Examples 1-2 reached swelling equilibrium within 24 hours, while the zwitterionic polymer-based hydrogel testicular prostheses provided in Comparative Example 3 reached swelling equilibrium within 120 hours and maintained constant mass over a long period of time. The swelling ratios of the zwitterionic polymer-based hydrogel testicular prostheses in Examples 1-8 were all lower than those in the Comparative Examples, indicating that the zwitterionic polymer-based hydrogel testicular prostheses provided in Examples 1-8 were more stable in PBS buffer than those in the Comparative Examples. These results demonstrate that the zwitterionic polymer-based hydrogel testicular prostheses provided in Examples 1-8 have excellent stability.

[0087] In summary, the zwitterionic polymer-based hydrogel testicular prosthesis provided in the embodiments of the present invention has excellent stability and mechanical properties, can meet practical application requirements, and can be applied in fields such as veterinary medicine.

[0088] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, rather than to limit it. Although the present invention has been described in detail with reference to the above embodiments, those skilled in the art should understand that they can still modify the technical solutions described in the above embodiments, or replace some or all of the technical features therein with equivalents. However, these modifications or replacements do not cause the essence of the corresponding technical solutions to deviate from the scope of the technical solutions of the embodiments of the present invention.

Claims

1. A hydrogel testicular prosthesis based on zwitterionic polymers, characterized in that: It is prepared from a raw material system including a zwitterionic monomer, N-acryloylureaamine and N-acryloylglycinamide, wherein the zwitterionic monomer is any one of the compounds represented by formula (1), formula (2), formula (3), formula (4), formula (5) and formula (6): Formula (1) Formula (2) Formula (3) Formula (4) Formula (5) Formula (6); The chemical structure of the N-acryloylureaamine is shown in formula (7): Formula (7); The chemical structure of the N-acryloylglycine amide is shown in formula (8): Formula (8).

2. The zwitterionic polymer-based hydrogel testicular prosthesis according to claim 1, characterized in that In the raw material system, the mass ratio of the N-acryloylureaamine, the N-acryloylglycineamide and the zwitterionic monomer is (1-3): (1-3): (0.1-2).

3. A method for preparing a zwitterionic polymer-based hydrogel testicular prosthesis according to claim 1 or 2, characterized in that: The steps include: Dissolving a zwitterionic monomer, N-acryloylureaamine and N-acryloylglycinamide in a mixed solvent, adding a photoinitiator and stirring to obtain a mixed solution; The mixed liquid is poured into a mold, irradiated under light, and then demoulded to obtain a colloid; The colloid is immersed in a buffer solution and reaches swelling equilibrium to obtain the hydrogel testicular prosthesis based on the zwitterionic polymer.

4. The method for preparing a zwitterionic polymer-based hydrogel testicular prosthesis according to claim 3, wherein: The mass ratio of the N-acryloylureaamine, the N-acryloylglycineamide and the zwitterionic monomer is (1-3): (1-3): (0.1-2).

5. The method for preparing a zwitterionic polymer-based hydrogel testicular prosthesis according to claim 3, characterized in that: In the mixed solution, the amount of the photoinitiator is 1% to 5% of the total amount of N-acryloylureaamine, N-acryloylglycineamide and zwitterionic monomer.

6. The method for preparing a zwitterionic polymer-based hydrogel testicular prosthesis according to claim 3, wherein: The photoinitiator is at least one of 2-hydroxy-2-methyl-1-phenyl-1-propanone, 2-hydroxy-4′-(2-hydroxyethoxy)-2-methylpropiophenone, and phenyl (2,4,6-trimethylbenzoyl) lithium phosphate.

7. The method for preparing a zwitterionic polymer-based hydrogel testicular prosthesis according to claim 3, characterized in that: In the mixed solution, the ratio of the total mass of N-acryloylureaamine, N-acryloylglycineamide and zwitterionic monomer to the mass of the mixed solvent is 0.3 to 1.

5.

8. The method for preparing a zwitterionic polymer-based hydrogel testicular prosthesis according to claim 3, wherein: The mixed solvent is prepared by mixing the following components in volume percentage: 60% to 80% deionized water and 20% to 40% dimethyl sulfoxide.

9. The method for preparing a zwitterionic polymer-based hydrogel testicular prosthesis according to claim 3, wherein: The light is ultraviolet light with a wavelength of 100nm to 400nm or blue light with a wavelength of 400nm to 500nm, and the irradiation time is 600s to 3600s.

10. The method for preparing a zwitterionic polymer-based hydrogel testicular prosthesis according to claim 3, characterized in that: The soaking time is 48 hours to 120 hours, and the temperature is 20° C. to 40° C.

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