A hydrogel testicular prosthesis based on zwitterionic polymer and its preparation method

Abstract

This invention relates to the field of medical biomaterials technology, and more particularly to a hydrogel testicular prosthesis based on a zwitterionic polymer and its preparation method. The hydrogel testicular prosthesis based on the zwitterionic polymer is prepared from a raw material system comprising a zwitterionic monomer, N-acryloylureaamine, and N-acryloylglycine. This hydrogel testicular prosthesis based on the zwitterionic polymer exhibits excellent stability and mechanical properties, meeting practical application requirements and applicable to fields such as veterinary medicine.

Description

Technical Field

[0001] This invention relates to the field of medical biomaterials technology, and in particular to a hydrogel testicular prosthesis based on zwitterionic polymers and its preparation method. Background Technology

[0002] In modern veterinary medicine, castration or sterilization of male animals refers to the removal of the testes to interrupt the secretion of sex hormones, thereby preventing testicular diseases (such as orchitis, testicular torsion, and testicular tumors). However, for male animals, orchiectomy not only results in the loss of a physiological organ but also causes psychological distress. The advent of testicular prostheses can, to some extent, compensate for the physiological and psychological deficiencies experienced by orchiectomized males.

[0003] A testicular prosthesis is a prosthesis that resembles a testis and can be implanted into the scrotum of a male animal. Most testicular prostheses on the market are currently made of silicone rubber. While silicone rubber prostheses can meet certain requirements for appearance and feel, the silicone rubber molecules are helical and have very low polarity, exhibiting strong hydrophobicity. This results in poor affinity with body tissues, making them prone to adverse reactions after implantation and leading to poor biocompatibility.

[0004] Hydrogels, as an emerging biomaterial, exhibit good biocompatibility due to their high water content, softness, and structure similar to biological tissues. Therefore, hydrogels are considered potential candidates to replace silicone rubber. However, due to their high water content, hydrogels may experience swelling, leakage, or degradation after prolonged implantation, leading to 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] This invention provides a hydrogel testicular prosthesis based on zwitterionic polymers. The hydrogel testicular prosthesis is prepared from a raw material system including zwitterionic monomers, N-acryloylureaamine and N-acryloylglycine, and has excellent stability and mechanical properties.

[0007] The present invention also provides a method for preparing a hydrogel testicular prosthesis based on zwitterionic polymers, which can be used to prepare the above-mentioned hydrogel testicular prosthesis based on zwitterionic polymers with excellent stability and mechanical properties.

[0008] A first aspect of the present invention provides a hydrogel testicular prosthesis based on a zwitterionic polymer, which is prepared from a raw material system comprising a zwitterionic monomer, N-acryloylureaamine and N-acryloylglycine, wherein the zwitterionic monomer is any one of the compounds shown in formula (1), formula (2), formula (3), formula (4), formula (5) and formula (6):

[0009] Equation (1)

[0010] Equation (2),

[0011] Equation (3)

[0012] Equation (4)

[0013] Equation (5),

[0014] Equation (6);

[0015] The chemical structural formula of the N-acryloylureaamine is shown in formula (7):

[0016] Equation (7);

[0017] The chemical structural formula of the N-acryloylglycine is shown in formula (8):

[0018] Equation (8).

[0019] In the above-mentioned hydrogel testicular prosthesis based on zwitterionic polymer, the mass ratio of N-acryloylurea, N-acryloylglycine and zwitterionic monomer in the raw material system is (1-3):(1-3):(0.1-2).

[0020] A second aspect of the present invention provides a method for preparing the aforementioned hydrogel testicular prosthesis based on zwitterionic polymers, comprising the following steps:

[0021] A zwitterionic monomer, N-acryloylureaamine and N-acryloylglycine were dissolved in a mixed solvent, a photoinitiator was added and the mixture was stirred to obtain a mixed solution;

[0022] The mixture is poured into a mold, irradiated under light, and then demolded to obtain a colloid.

[0023] The colloid is immersed in a buffer solution and swells to reach equilibrium, thus obtaining the hydrogel testicular prosthesis based on zwitterionic polymers.

[0024] In the preparation method of the hydrogel testicular prosthesis based on zwitterionic polymer as described above, the mass ratio of N-acryloylurea, N-acryloylglycine and zwitterionic monomer is (1-3):(1-3):(0.1-2).

[0025] In the preparation method of the hydrogel testicular prosthesis based on zwitterionic polymers as described above, the amount of photoinitiator in the mixture is 1% to 5% of the total amount of N-acryloylurea, N-acryloylglycine and zwitterionic monomers.

[0026] In the preparation method of the hydrogel testicular prosthesis based on zwitterionic polymers as described above, the photoinitiator is at least one of 2-hydroxy-2-methyl-1-phenyl-1-propanone, 2-hydroxy-4′-(2-hydroxyethoxy)-2-methylphenylpropanone, and lithium phenyl (2,4,6-trimethylbenzoyl)phosphate.

[0027] In the preparation method of the hydrogel testicular prosthesis based on zwitterionic polymers as described above, the ratio of the total mass of N-acryloylurea, N-acryloylglycine and zwitterionic monomers to the mass of the mixed solvent in the mixture is 0.3 to 1.5.

[0028] The preparation method of the hydrogel testicular prosthesis based on zwitterionic polymer as described above, wherein the mixed solvent is composed of the following components by volume percentage: 60%–80% deionized water and 20%–40% dimethyl sulfoxide.

[0029] In the preparation method of hydrogel testicular prostheses based on zwitterionic polymers as described above, 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.

[0030] In the preparation method of hydrogel testicular prostheses based on zwitterionic polymers as described above, the soaking time is 48h to 120h and the temperature is 20℃ to 40℃.

[0031] The beneficial technical effects of the present invention include at least the following:

[0032] The hydrogel testicular prosthesis based on zwitterionic polymers provided by this invention is prepared from a raw material system comprising zwitterionic monomers, N-acryloylureaamine, and N-acryloylglycine. This zwitterionic polymer-based hydrogel testicular prosthesis exhibits excellent stability and mechanical properties. Firstly, compared to testicular prostheses made from traditional silicone rubber materials, the zwitterionic polymer-based hydrogel testicular prosthesis provided by this invention has good biocompatibility, which is beneficial for improving the affinity between the zwitterionic polymer-based hydrogel testicular prosthesis and body tissues, reducing adverse reactions after implantation. Secondly, the zwitterionic polymer-based hydrogel testicular prosthesis has excellent stability, which is beneficial for improving the long-term effectiveness and safety of the zwitterionic polymer-based hydrogel testicular prosthesis, reducing the frequency of replacement or repair. Thirdly, the zwitterionic polymer-based hydrogel testicular prosthesis has excellent mechanical properties (0.19-0.32 MPa), matching the modulus of natural testes, and can effectively withstand external pressure and impact, preventing deformation or damage to the prosthesis after implantation. Attached Figure Description

[0033] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0034] Figure 1 The image shows the 1H NMR spectrum of N-acryloylureaamine (NASC) in this invention.

[0035] Figure 2 The image shows the 1H NMR spectrum of N-acryloylglycine (NAGA) in this invention.

[0036] Figure 3 The 1H NMR spectrum of 2-((2-hydroxy-3-(methacryloyloxy)propyl)dimethylamino)acetate (CB-OH) in this invention;

[0037] Figure 4 This is an external image of the hydrogel testicular prosthesis based on zwitterionic polymer in Embodiment 1 of the present invention;

[0038] Figure 5 This is a schematic diagram of the molecular chain of the hydrogel testicular prosthesis based on zwitterionic polymer in Embodiment 1 of the present invention;

[0039] Figure 6 The swelling curve of the hydrogel testicular prosthesis based on zwitterionic polymer in Example 1 of this invention;

[0040] Figure 7 The swelling curve of the hydrogel testicular prosthesis based on zwitterionic polymer in Example 2 of this invention;

[0041] Figure 8 The swelling curve of the hydrogel testicular prosthesis based on zwitterionic polymer in Example 3 of this invention;

[0042] Figure 9 The swelling curve of the hydrogel testicular prosthesis based on zwitterionic polymer in Example 4 of this invention;

[0043] Figure 10 The swelling curve of the hydrogel testicular prosthesis based on zwitterionic polymer in Example 5 of this invention;

[0044] Figure 11 The swelling curve of the hydrogel testicular prosthesis based on zwitterionic polymer in Example 6 of this invention;

[0045] Figure 12 The swelling curve of the hydrogel testicular prosthesis based on zwitterionic polymer in Example 7 of this invention;

[0046] Figure 13 The swelling curve of the hydrogel testicular prosthesis based on zwitterionic polymer in Example 8 of this invention;

[0047] Figure 14 The swelling curve of the hydrogel testicular prosthesis based on zwitterionic polymer in Comparative Example 1 of this invention is shown.

[0048] Figure 15 The swelling curve of the hydrogel testicular prosthesis based on zwitterionic polymer in Comparative Example 2 of this invention is shown.

[0049] Figure 16 The swelling curve of the hydrogel testicular prosthesis based on zwitterionic polymer in Comparative Example 3 of this invention is shown. Detailed Implementation

[0050] To make the objectives, technical solutions, and advantages of this invention clearer, the technical solutions in the embodiments of this invention will be clearly and completely described below in conjunction with the embodiments of this invention. Obviously, the described embodiments are only some embodiments of this invention, not all embodiments. Based on the embodiments of this invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of this invention.

[0051] Unless otherwise specified, the raw materials and reagents used in the following examples are commercially available; and the processes used are conventional processes in the art.

[0052] A first aspect of the present invention provides a hydrogel testicular prosthesis based on a zwitterionic polymer, which is prepared from a raw material system comprising a zwitterionic monomer, N-acryloylureaamine and N-acryloylglycine, wherein the zwitterionic monomer is any one of the compounds shown in formula (1), formula (2), formula (3), formula (4), formula (5) and formula (6):

[0053] Equation (1)

[0054] Equation (2),

[0055] Equation (3)

[0056] Equation (4)

[0057] Equation (5),

[0058] Equation (6);

[0059] The chemical structural formula of the N-acryloylureaamine is shown in formula (7):

[0060] Equation (7);

[0061] The chemical structural formula of the N-acryloylglycine is shown in formula (8):

[0062] Equation (8).

[0063] In this invention, the aforementioned zwitterionic monomer refers to a monomer that carries both positive and negative charges.

[0064] This invention utilizes a polymer system comprising the aforementioned zwitterionic monomers, N-acryloylureaamine, and N-acryloylglycine to facilitate the preparation of hydrogel testicular prostheses based on zwitterionic polymers that possess excellent stability and mechanical properties.

[0065] In one specific embodiment, the mass ratio of N-acryloylureaamine, N-acryloylglycineamide, and zwitterionic monomer in the above raw material system 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.

[0066] When the mass ratio of N-acryloylurea, N-acryloylglycine and zwitterionic monomer in the above raw material system is within the above range, the zwitterionic monomer can undergo a polymerization reaction with N-acryloylurea and N-acryloylglycine, which is beneficial for preparing hydrogel testicular prostheses based on zwitterionic polymers.

[0067] Furthermore, in the above raw material system, the mass ratio of N-acryloylureaamine, N-acryloylglycineamide and zwitterionic monomer can preferably be 2:2:1.

[0068] When the mass ratio of N-acryloylurea, N-acryloylglycine and zwitterionic monomer in the above raw material system is 2:2:1, N-acryloylurea, N-acryloylglycine and zwitterionic monomer can fully undergo polymerization reaction, which is beneficial to preparing hydrogel testicular prostheses based on zwitterionic polymers with excellent stability and mechanical properties.

[0069] A second aspect of the present invention provides a method for preparing the above-mentioned hydrogel testicular prosthesis based on zwitterionic polymers, comprising the following steps:

[0070] A zwitterionic monomer, N-acryloylureaamine and N-acryloylglycine were dissolved in a mixed solvent, a photoinitiator was added and the mixture was stirred to obtain a mixed solution;

[0071] The mixture is poured into a mold, exposed to light, and then demolded to obtain a colloid.

[0072] The colloid is immersed in a buffer solution and swells to reach equilibrium, thus obtaining a hydrogel testicular prosthesis based on zwitterionic polymers.

[0073] The present invention does not impose any particular limitation on the specific material of the mold, and the material can be selected according to actual needs. In some embodiments, the mold can be a polydimethylsiloxane mold.

[0074] The present invention does not impose any particular limitation on the specific sources of the raw materials and reagents used in the preparation of hydrogel testicular prostheses based on zwitterionic polymers. They can be purchased through commercial channels or prepared by methods known in the art.

[0075] The present invention does not impose a specific limit on the amount of buffer solution used, and can be selected according to actual needs.

[0076] Specifically, this invention first dissolves N-acryloylurea, N-acryloylglycine, and zwitterionic monomers in a mixed solvent to obtain a mixed solution. Next, a photoinitiator is added to the mixed solution and stirred to obtain a second mixture. The photoinitiator is used to initiate the polymerization reaction during subsequent light irradiation. Stirring ensures the photoinitiator is fully dissolved in the mixed solution and a homogeneous second mixture is obtained. The stirred second mixture is poured into a mold and then irradiated under light to initiate the polymerization reaction of N-acryloylurea, N-acryloylglycine, and zwitterionic monomers. After the polymerization reaction is complete, a gel-like substance is obtained. The gel-like substance is removed from the mold to obtain a colloid. The colloid is then immersed in a buffer solution. Through immersion, the colloid absorbs water and swells, eventually reaching swelling equilibrium, resulting in a hydrogel testicular prosthesis based on a zwitterionic polymer that possesses both excellent stability and mechanical properties.

[0077] The principle of the present invention is explained as follows: N-acryloylurea, N-acryloylglycine and zwitterionic monomers all contain a carbon-carbon double bond (C=C) in their structure. N-acryloylurea, N-acryloylglycine and zwitterionic monomers can undergo free radical polymerization to form polymer molecular chains, and form a three-dimensional network structure through hydrogen bonding to form a hydrogel.

[0078] The polymerization process described above is as follows: When the photoinitiator is exposed to light, it generates active free radicals. These active free radicals attack the carbon-carbon double bonds (C=C) of the double-bonded monomers (N-acryloylurea, N-acryloylglycine, and zwitterionic monomers), causing the π bonds to break and forming monomer free radicals. These monomer free radicals react with new monomer molecules (N-acryloylurea, N-acryloylglycine, and zwitterionic monomers) to form longer chain free radicals through the breaking of double bonds.

[0079] In one specific embodiment, the mass ratio of the above-mentioned N-acryloylureaamine, the above-mentioned N-acryloylglycineamide and the above-mentioned zwitterionic monomer is (1-3):(1-3):(0.1-2), which is preferably 2:2:1.

[0080] When the mass ratio of N-acryloylurea, N-acryloylglycine and zwitterionic monomer is within the above range, the zwitterionic monomer can undergo a polymerization reaction with N-acryloylurea and N-acryloylglycine, which is beneficial for preparing hydrogel testicular prostheses based on zwitterionic polymers.

[0081] In one specific embodiment, the amount of photoinitiator in the above mixture is 1% to 5% of the total amount of N-acryloylureaamine, N-acryloylglycineamide and zwitterionic monomer.

[0082] When the amount of photoinitiator in the mixture is within the range of the parameters for the total amount of N-acryloylurea, N-acryloylglycine, and zwitterionic monomers, the N-acryloylurea, N-acryloylglycine, zwitterionic monomers, and photoinitiator in the second mixture can be better matched, allowing the polymerization reaction to proceed more fully. This is beneficial for preparing hydrogel testicular prostheses based on zwitterionic polymers that have both excellent stability and mechanical properties.

[0083] In one specific embodiment, the photoinitiator is at least one of 2-hydroxy-2-methyl-1-phenyl-1-propanone, 2-hydroxy-4′-(2-hydroxyethoxy)-2-methylphenylpropanone, and lithium phenyl (2,4,6-trimethylbenzoyl)phosphate, preferably 2-hydroxy-2-methyl-1-phenyl-1-propanone.

[0084] When the above-mentioned substances are selected as photoinitiators, they can promote the polymerization reaction between N-acryloylurea, N-acryloylglycine and zwitterionic monomers in the mixture, which is beneficial to the subsequent preparation of hydrogel testicular prostheses based on zwitterionic polymers with excellent stability and mechanical properties.

[0085] In one specific embodiment, the ratio of the total mass of N-acryloylureaamine, N-acryloylglycineamide, and zwitterionic monomers to the mass of the mixed solvent in the above mixture is 0.3 to 1.5.

[0086] The above-mentioned mixed solvent is composed of 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.

[0087] When the ratio of the total mass of N-acryloylurea, N-acryloylglycine and zwitterionic monomers to the mass of the mixed solvent in the above mixture is within the above range, and when the mixed solvent composed of the above deionized water and dimethyl sulfoxide is selected, the solubility of N-acryloylurea, N-acryloylglycine and zwitterionic monomers in the mixed solvent can be controlled, thereby preparing hydrogel testicular prostheses based on zwitterionic polymers with different mechanical properties.

[0088] In one specific embodiment, 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.

[0089] When the above-mentioned light is selected for irradiation and the irradiation time is within the above-mentioned range, the photoinitiator can be effectively excited to generate free radicals, thereby initiating a full polymerization reaction between N-acryloylureaamine, N-acryloylglycineamide and zwitterionic monomers, which is beneficial for preparing hydrogel testicular prostheses based on zwitterionic polymers.

[0090] In one specific embodiment, the soaking time is 48h to 120h and the temperature is 20 to 40°C.

[0091] When the soaking time and temperature parameters are within the above range, it is to allow the colloid to fully absorb water and reach swelling equilibrium, so as to obtain a hydrogel testicular prosthesis based on zwitterionic polymer that has both excellent stability and mechanical properties.

[0092] In one specific embodiment, the buffer solution comprises a phosphate buffer solution.

[0093] The present invention will be further described below through specific embodiments.

[0094] The carboxybetaine urea acrylate (CBUIA) used in the following examples was synthesized according to the method described 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)); the carboxybetaine carbamate acrylate (CBUTA) was synthesized according to the method described 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)).

[0095] Preparation of N-acryloylureaamine (NASC):

[0096] 12.7 g of ureaamine hydrochloride, 12 mL of deionized water, and 67.2 mL of potassium carbonate solution (2 mol / L) were added sequentially to a round-bottom flask under ice bath conditions. Then, 36 mL of ice-cold diethyl ether was added to obtain a mixed solution. 11.4 g of acryloyl chloride was dissolved in 48 mL of diethyl ether to obtain an acryloyl chloride-containing ether solution. This acryloyl chloride-containing ether solution was then slowly added dropwise to the above mixed solution, with the mixture stirred using a magnetic stirrer throughout the process, all under ice bath conditions. After the acryloyl chloride-containing ether solution had been added, a mixed solution was obtained. The mixed solution was then placed under ice bath conditions. Stirring continued for 4 hours, during which a large amount of white precipitate was generated. After the reaction was complete, the mixture was filtered to remove the solvent, retaining the white precipitate. The white precipitate was then washed with cold water by centrifugation, the supernatant was removed, and the lower precipitate was retained to obtain the 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 was transferred to a lyophilization box, cooled to room temperature, and then frozen at -50°C. Finally, it was freeze-dried to obtain the white, pure product, N-acryloylureamine (NASC). The 1H NMR spectrum of NASC is shown below. Figure 1 As shown, the chemical structural formula of NASC is as follows:

[0097]

[0098] Preparation of N-acryloylglycine (NAGA):

[0099] Weigh 6.30 g of glycine hydrochloride powder and add it to a 250 mL single-necked round-bottom flask. Then, place the single-necked round-bottom flask in an ice-water bath and add 6 mL of deionized water, 33.6 mL of 2 mol / L potassium carbonate aqueous solution and 18 mL of anhydrous diethyl ether to the single-necked round-bottom flask in sequence. Stir in the ice bath until the glycine hydrochloride powder is completely dissolved.

[0100] Add 24 mL of anhydrous diethyl ether to a 50 mL constant pressure dropping funnel, and add 5.7 mL of acryloyl chloride to obtain diluted acryloyl chloride. Under ice-water bath stirring conditions, adjust the knob of the constant pressure dropping funnel to slowly add the diluted acryloyl chloride dropwise to a round bottom flask. After the addition is complete, maintain the ice-water bath environment and continue stirring the reaction for 4 hours to obtain the reaction solution.

[0101] The reaction solution was adjusted to pH 2 with a 2 mol / L dilute hydrochloric acid solution, and then extracted three times with 50 mL of anhydrous diethyl ether. The aqueous phase was retained to remove the organic phase (anhydrous diethyl ether) and organic impurities (such as acrylates) in the aqueous phase, thus obtaining the extracted aqueous phase.

[0102] The aqueous phase reaction solution after extraction was adjusted to pH=7 with a 2 mol / L NaOH solution, frozen in an ultra-low temperature freezer, and then 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 stirred vigorously to ensure that the crude product was fully dispersed in the mixed solvent to obtain a mixture. Then, the insoluble matter in the mixture was removed by vacuum filtration to obtain a filtrate. The filtrate was then subjected to rotary evaporation at 35 °C to obtain a concentrated solution. The concentrated solution was then placed in a -20 °C freezer for recrystallization for 20 min and then filtered to obtain a white product.

[0103] The white product was dried under vacuum to obtain purified N-acryloylglycine (NAGA). The 1H NMR spectrum of NAGA is shown below. Figure 2 As shown, the chemical structural formula of NAGA is as follows:

[0104]

[0105] Preparation of 2-((2-hydroxy-3-(methacryloyloxy)propyl)dimethylamino)acetate (CB-OH):

[0106] 9.37 g of tert-butyl sarcosine hydrochloride was dissolved in 60 mL of water and neutralized with 5 g of sodium bicarbonate to obtain tert-butyl sarcosine. The tert-butyl sarcosine was extracted with 60 mL of dichloromethane, and the solvent was then evaporated to obtain 7.4 g of purified tert-butyl sarcosine. The 7.4 g of purified tert-butyl sarcosine, 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 h to obtain the reaction product. The reaction product was filtered to remove insoluble magnesium sulfate, yielding a filtrate. The filtrate was mixed with 140 mL of iodomethane (the volume ratio of iodomethane to filtrate was 4:1). 1) A methylation reaction was performed to form white CB-OH-tBu crystals. The CB-OH-tBu crystals were washed with diethyl ether, dried under vacuum, and then dissolved in trifluoroacetic acid (TFA) for 2 hours to completely deprotect the tBu groups, yielding the product. The product was precipitated in diethyl ether, 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 was washed three times with dichloromethane and lyophilized to obtain a white powder, namely 2-((2-hydroxy-3-(methacryloyloxy)propyl)dimethylamino)acetate (CB-OH). The 1H NMR spectrum of CB-OH is shown below. Figure 3 As shown, the chemical structural formula of CB-OH is as follows:

[0107]

[0108] Example 1

[0109] The method for preparing a hydrogel testicular prosthesis based on zwitterionic polymers provided in this embodiment includes the following steps:

[0110] (1) Dissolve 2g of N-acryloylurea (NASC), 2g of N-acryloylglycine (NAGA) and 1g of 2-((2-hydroxy-3-(methacryloyloxy)propyl)dimethylamino)acetate (CB-OH) in 10g of mixed solvent (which is a mixture of 70% deionized water and 30% dimethyl sulfoxide by volume percentage), then add 23.5μL of 2-hydroxy-2-methyl-1-phenyl-1-propanone (CAS No.: 7473-98-5) and stir thoroughly to obtain a homogeneous mixture.

[0111] (2) Pour the mixture into a polydimethylsiloxane mold, irradiate it under ultraviolet light with a wavelength of 310 nm for 3600 s, and then demold to obtain a colloid.

[0112] (3) The colloid is immersed in a phosphate buffer solution at 37°C for 72 hours until swelling equilibrium is reached, and then the product is obtained. Figure 4 The hydrogel testicular prosthesis based on zwitterionic polymers shown is illustrated in the schematic diagram of its molecular chain. Figure 5 As shown.

[0113] Example 2

[0114] The preparation method of the hydrogel testicular prosthesis based on zwitterionic polymers provided in this embodiment is basically the same as that in Example 1, except that:

[0115] (1) Replace 1g of 2-((2-hydroxy-3-(methacryloyloxy)propyl)dimethylamino)acetate (CB-OH) with 0.1g of 2-((2-hydroxy-3-(methacryloyloxy)propyl)dimethylamino)acetate (CB-OH).

[0116] Example 3

[0117] The preparation method of the hydrogel testicular prosthesis based on zwitterionic polymers provided in this embodiment is basically the same as that in Example 1, except that:

[0118] (1) Replace 1g of 2-((2-hydroxy-3-(methacryloyloxy)propyl)dimethylamino)acetate (CB-OH) with 2g of 2-((2-hydroxy-3-(methacryloyloxy)propyl)dimethylamino)acetate (CB-OH).

[0119] Example 4

[0120] The preparation method of the hydrogel testicular prosthesis based on zwitterionic polymers provided in this embodiment is basically the same as that in Example 1, except that:

[0121] Replace 2-((2-hydroxy-3-(methacryloyloxy)propyl)dimethylamino)acetate (CB-OH) with carboxybenzene urea acrylate (CBUIA). The chemical structure of CBUIA is as follows:

[0122]

[0123] Example 5

[0124] The preparation method of the hydrogel testicular prosthesis based on zwitterionic polymers provided in this embodiment is basically the same as that in Example 1, except that:

[0125] Replace 2-((2-hydroxy-3-(methacryloyloxy)propyl)dimethylamino)acetate (CB-OH) with carboxybenzene carbamate acrylate (CBUTA). The chemical structure of CBUTA is as follows:

[0126]

[0127] Example 6

[0128] The preparation method of the hydrogel testicular prosthesis based on zwitterionic polymers provided in this embodiment is basically the same as that in Example 1, except that:

[0129] Replace 2-((2-hydroxy-3-(methacryloyloxy)propyl)dimethylamino)acetate (CB-OH) with carboxybetaine acrylamide (CBAA). The chemical structure of CBAA is as follows:

[0130]

[0131] Example 7

[0132] The preparation method of the hydrogel testicular prosthesis based on zwitterionic polymers provided in this embodiment is basically the same as that in Example 1, except that:

[0133] Replace 2-((2-hydroxy-3-(methacryloyloxy)propyl)dimethylamino)acetate (CB-OH) with 2-methacryloyloxyethylphosphorylcholine (MPC). The chemical structure of MPC is as follows:

[0134]

[0135] Example 8

[0136] The preparation method of the hydrogel testicular prosthesis based on zwitterionic polymers provided in this embodiment is basically the same as that in Example 1, except that:

[0137] Replace 2-((2-hydroxy-3-(methacryloyloxy)propyl)dimethylamino)acetate (CB-OH) with carboxylic acid betaine (CBMA). The chemical structure of CBMA is as follows:

[0138]

[0139] Comparative Example 1

[0140] The method for preparing a hydrogel testicular prosthesis based on zwitterionic polymers provided in this comparative example includes the following steps:

[0141] (1) Dissolve 2g of N-acryloylurea (NASC), 2g of N-acryloylglycine (NAGA) and 1g of 2-((2-hydroxy-3-(methacryloyloxy)propyl)dimethylamino)acetate (CB-OH) in 10g of mixed solvent (which is a mixture of 70% deionized water and 30% dimethyl sulfoxide by volume percentage), then add 27.8μL of 2-hydroxy-4′-(2-hydroxyethoxy)-2-methylphenylacetone (CAS No.: 106797-53-9) and stir thoroughly to obtain a homogeneous mixture.

[0142] (2) Pour the mixture into a polydimethylsiloxane mold, irradiate it under ultraviolet light with a wavelength of 310 nm for 3600 s, and then demold to obtain a colloid.

[0143] (3) The colloid is soaked in a phosphate buffer solution at 37°C for 72 hours. After swelling equilibrium is reached, a hydrogel testicular prosthesis based on zwitterionic polymer is obtained.

[0144] Comparative Example 2

[0145] The method for preparing a hydrogel testicular prosthesis based on zwitterionic polymers provided in this comparative example includes the following steps:

[0146] (1) Dissolve 2g of N-acryloylurea (NASC), 2g of N-acryloylglycine (NAGA) and 1g of 2-((2-hydroxy-3-(methacryloyloxy)propyl)dimethylamino)acetate (CB-OH) in 10g of mixed solvent (which is a mixture of 70% deionized water and 30% dimethyl sulfoxide by volume percentage), then add 0.5g of phenyl (2,4,6-trimethylbenzoyl)lithium phosphate (CAS No.: 85073-19-4) and stir thoroughly to obtain a homogeneous mixture.

[0147] (2) Pour the mixture into a polydimethylsiloxane mold, irradiate it under ultraviolet light with a wavelength of 310 nm for 3600 s, and then demold to obtain a colloid.

[0148] (3) The colloid is soaked in a phosphate buffer solution at 37°C for 72 hours. After swelling equilibrium is reached, a hydrogel testicular prosthesis based on zwitterionic polymer is obtained.

[0149] Comparative Example 3 (without N-acryloylglycine and N-acryloylurea)

[0150] The preparation method of the hydrogel testicular prosthesis based on zwitterionic polymers provided in this embodiment is basically the same as that in Example 1, except that:

[0151] (1) Dissolve 1g of 2-((2-hydroxy-3-(methacryloyloxy)propyl)dimethylamino)acetate (CB-OH) in 5g of pure water, then add 23.5μL of 2-hydroxy-2-methyl-1-phenyl-1-propanone (CAS No.: 7473-98-5) and stir thoroughly to obtain a homogeneous mixture.

[0152] Comparative Example 4 (without N-acryloylglycine)

[0153] The preparation method of the hydrogel testicular prosthesis based on zwitterionic polymers provided in this comparative example is basically the same as that in Example 1, except that:

[0154] (1) Dissolve 2g of N-acryloylurea (NASC) and 1g of 2-((2-hydroxy-3-(methacryloyloxy)propyl)dimethylamino)acetate (CB-OH) in 10g of mixed solvent (which is a mixture of 70% deionized water and 30% dimethyl sulfoxide by volume percentage), then add 23.5μL of 2-hydroxy-2-methyl-1-phenyl-1-propanone (CAS No.: 7473-98-5) and stir thoroughly to obtain a homogeneous mixture.

[0155] During the preparation of the zwitterionic polymer-based hydrogel testicular prosthesis in this comparative example, the inventors discovered that the uniform mixture in this comparative example could not form a gel, therefore no subsequent performance tests were conducted.

[0156] Comparative Example 5 (without N-acryloylureaamine)

[0157] The preparation method of the hydrogel testicular prosthesis based on zwitterionic polymers provided in this comparative example is basically the same as that in Example 1, except that:

[0158] (1) Dissolve 2g of N-acryloylglycine (NAGA) and 1g of 2-((2-hydroxy-3-(methacryloyloxy)propyl)dimethylamino)acetate (CB-OH) in 10g of mixed solvent (which is a mixture of 70% deionized water and 30% dimethyl sulfoxide by volume percentage), then add 23.5μL of 2-hydroxy-2-methyl-1-phenyl-1-propanone (CAS No.: 7473-98-5) and stir thoroughly to obtain a homogeneous mixture.

[0159] During the preparation of the zwitterionic polymer-based hydrogel testicular prosthesis in this comparative example, the inventors discovered that the uniform mixture in this comparative example could not form a gel, therefore no subsequent performance tests were conducted.

[0160] Comparative Example 6

[0161] The preparation method of the hydrogel testicular prosthesis based on zwitterionic polymers provided in this comparative example is basically the same as that in Example 1, except that:

[0162] (1) Dissolve 2g of N-acryloylurea (NASC), 2g of N-acryloylglycine (NAGA) and 5g of 2-((2-hydroxy-3-(methacryloyloxy)propyl)dimethylamino)acetate (CB-OH) in 10g of mixed solvent (which is a mixture of 70% deionized water and 30% dimethyl sulfoxide by volume percentage), then add 23.5μL of 2-hydroxy-2-methyl-1-phenyl-1-propanone (CAS No.: 7473-98-5) and stir thoroughly to obtain a homogeneous mixture.

[0163] During the preparation of the homogeneous mixture in this comparative example, the inventors discovered that the mixture of N-acryloylureaamine (NASC), N-acryloylglycine (NAGA) and 2-((2-hydroxy-3-(methacryloyloxy)propyl)dimethylamino)acetic acid ester could not be completely dissolved, and the homogeneous mixture could not form a gel. Therefore, no subsequent performance tests were conducted.

[0164] Performance testing

[0165] 1. Mechanical properties

[0166] The following tests were performed on the hydrogel testicular prostheses based on zwitterionic polymers in Examples 1-8 and Comparative Examples 1-3 of the present invention, and the test results are shown in Table 1 and Table 2.

[0167] Strength (MPa): The test method is in accordance with the national standard GB / T 528-2009.

[0168] Table 1 Test Results

[0169]

[0170] Table 2 Test Results

[0171]

[0172] As shown in Tables 1 and 2, the hydrogel testicular prosthesis based on zwitterionic polymers provided in the embodiments of the present invention has excellent mechanical properties (strength up to 0.32 MPa).

[0173] 2. Stability

[0174] The stability of the hydrogel testicular prostheses based on zwitterionic polymers in Examples 1-8 and Comparative Examples 1-3 of the present invention was tested. The specific method is as follows: 1 gram (g) of the hydrogel testicular prosthesis based on zwitterionic polymers was immersed in PBS buffer, the time-mass swelling curve was recorded and the swelling ratio was calculated (the calculation results are shown in Tables 3 and 4), so as to evaluate the stability of the hydrogel testicular prostheses based on zwitterionic polymers.

[0175] Swelling ratio = equilibrium swelling mass / initial mass.

[0176] Table 3 Swelling Ratio

[0177]

[0178] Table 4 Swelling Ratio

[0179]

[0180] A lower swelling ratio indicates better material stability. Figures 6-16 As shown in Tables 3-4, the hydrogel testicular prostheses based on zwitterionic polymers provided in Examples 1-8 and Comparative Examples 1-2 reached swelling equilibrium within 24 hours, while the hydrogel testicular prosthesis based on zwitterionic polymers provided in Comparative Example 3 reached swelling equilibrium within 120 hours, and maintained constant mass over a long period. The swelling ratios of the hydrogel testicular prostheses based on zwitterionic polymers in Examples 1-8 were all lower than those in the comparative examples, indicating that the stability of the hydrogel testicular prostheses based on zwitterionic polymers provided in the examples of the present invention in PBS buffer is higher than that in the comparative examples. These results demonstrate that the hydrogel testicular prostheses based on zwitterionic polymers provided in the examples of the present invention possess excellent stability.

[0181] In summary, the hydrogel testicular prosthesis based on zwitterionic polymers provided in this invention has excellent stability and mechanical properties, which can meet the needs of practical applications and can be applied to fields such as veterinary medicine.

[0182] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, and not to limit them; although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some or all of the technical features; and these modifications or substitutions 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, The hydrogel testicular prosthesis is prepared by a method comprising the following steps: dissolving N-acryloylurea, N-acryloylglycine and zwitterionic monomers in a mixed solvent at a mass ratio of (1-3):(1-3):(0.1-2), adding a photoinitiator and stirring to obtain a mixture; pouring the mixture into a mold, irradiating it under light, and then demolding it to obtain a colloid; immersing the colloid in a buffer solution until swelling equilibrium is reached to obtain the final product. The zwitterionic monomer is any one of the compounds shown in formula (1), formula (2), formula (3), formula (4), formula (5), and formula (6): Equation (1) Equation (2), Equation (3) Equation (4) Equation (5), Equation (6); The chemical structural formula of the N-acryloylureaamine is shown in formula (7): Equation (7); The chemical structural formula of the N-acryloylglycine is shown in formula (8): Equation (8); The photoinitiator is 2-hydroxy-2-methyl-1-phenyl-1-propanone.

2. A method for preparing a hydrogel testicular prosthesis based on zwitterionic polymers as described in claim 1, characterized in that, Includes the following steps: N-Acryloylureaamine, N-Acryloylglycineamide and zwitterionic monomers were dissolved in a mixed solvent at a mass ratio of (1-3):(1-3):(0.1-2), a photoinitiator was added and the mixture was stirred to obtain a mixed solution; the photoinitiator was 2-hydroxy-2-methyl-1-phenyl-1-propanone. The mixture is poured into a mold, irradiated under light, and then demolded to obtain a colloid. The colloid is immersed in a buffer solution and swells to reach equilibrium, thus obtaining the hydrogel testicular prosthesis based on zwitterionic polymers.

3. The method for preparing a hydrogel testicular prosthesis based on zwitterionic polymers according to claim 2, characterized in that, In the mixture, the amount of photoinitiator is 1% to 5% of the total amount of N-acryloylurea, N-acryloylglycine and zwitterionic monomer.

4. The method for preparing a hydrogel testicular prosthesis based on zwitterionic polymers according to claim 2, characterized in that, In the mixture, the ratio of the total mass of N-acryloylureaamine, N-acryloylglycineamide, and zwitterionic monomers to the mass of the mixed solvent is 0.3 to 1.

5.

5. The method for preparing a hydrogel testicular prosthesis based on zwitterionic polymers according to claim 2, characterized in that, The mixed solvent is composed of the following components by volume percentage: 60%–80% deionized water and 20%–40% dimethyl sulfoxide.

6. The method for preparing a hydrogel testicular prosthesis based on zwitterionic polymers according to claim 2, characterized in that, The light is ultraviolet light with a wavelength of 100nm to 400nm, and the irradiation time is 600s to 3600s.

7. The method for preparing a hydrogel testicular prosthesis based on zwitterionic polymers according to claim 2, characterized in that, The soaking time is 48h to 120h, and the temperature is 20℃ to 40℃.

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