Vinyl pyrrolidone copolymer as well as preparation method and application thereof

Abstract

The invention relates to a vinyl pyrrolidone copolymer as well as a preparation method and application thereof, and belongs to the technical field of high polymer materials. The vinyl pyrrolidone copolymer is prepared from the following raw materials: N-vinyl pyrrolidone, a hydrophilic monomer containing carboxyl, an antibacterial monomer containing a quaternary ammonium salt group and a degradable monomer containing an ester bond. The vinyl pyrrolidone copolymer provided by the invention has excellent biocompatibility, antibacterial property and controllable degradability, and well meets the multi-dimensional requirements of medical materials or daily chemical products.

Description

Technical Field

[0001] This invention relates to the field of polymer materials technology, and in particular to a vinylpyrrolidone copolymer, its preparation method, and its application. Background Technology

[0002] Polyvinyl pyrrolidone (PVP), a homopolymer of N-vinyl-2-pyrrolidone (NVP), has been widely used in pharmaceuticals and daily chemicals due to its excellent water solubility, biocompatibility, and film-forming properties. However, existing PVP materials suffer from limited functionality: pure PVP lacks antibacterial activity, easily leading to microbial growth in medical settings; its capacity for loading hydrophobic drugs is also weak, limiting its application as a drug carrier; furthermore, the degradation rate of conventional PVP is difficult to control, potentially posing a risk of metabolic accumulation during in vivo application.

[0003] To address these issues, existing technologies often employ copolymerization of NVP with acrylic monomers. However, the biocompatibility of these copolymers is easily affected by carboxyl groups, and the improvement in antibacterial properties is limited. Additionally, introducing antibacterial components through physical blending to enhance antibacterial performance suffers from uneven dispersion and easy precipitation, resulting in poor material stability.

[0004] Therefore, developing a vinylpyrrolidone copolymer that combines excellent biocompatibility, controllable degradation, and high-efficiency antibacterial properties has become an urgent problem to be solved. Summary of the Invention

[0005] To address the aforementioned technical problems, this invention provides a vinylpyrrolidone copolymer, its preparation method, and its applications. The vinylpyrrolidone copolymer exhibits excellent biocompatibility, antibacterial properties, and controllable degradation, effectively meeting the diverse needs of medical materials and daily chemical products.

[0006] To achieve this objective, the present invention adopts the following technical solution:

[0007] In a first aspect, the present invention provides a vinylpyrrolidone copolymer, wherein the raw materials for preparing the vinylpyrrolidone copolymer include N-vinylpyrrolidone, a hydrophilic monomer containing a carboxyl group, an antibacterial monomer containing a quaternary ammonium salt group, and a biodegradable monomer containing an ester bond.

[0008] This invention optimizes the design of raw materials for preparing vinylpyrrolidone copolymers. Using NVP as the core monomer, it combines it with hydrophilic monomers containing carboxyl groups, antibacterial monomers containing quaternary ammonium salt groups, and biodegradable monomers containing ester bonds. This achieves the design of the molecular structure of vinylpyrrolidone copolymers, thus breaking through the single-function limitations of traditional vinylpyrrolidone copolymers. It integrates biocompatibility (NVP, acrylic acid), antibacterial properties (quaternary ammonium salt), and controllable degradation (ester monomers) into the same molecular structure, solving the multi-dimensional needs of medical materials or daily chemical products and effectively expanding the application boundaries of NVP-based polymers.

[0009] The following are preferred technical solutions of the present invention, but are not intended to limit the technical solutions provided by the present invention. The purpose and beneficial effects of the present invention can be better achieved and realized through the following preferred technical solutions.

[0010] As a preferred embodiment of the present invention, the raw materials for preparing the vinylpyrrolidone copolymer include the following components in parts by weight:

[0011] 30-50 parts of N-vinylpyrrolidone;

[0012] 10-20 parts of hydrophilic monomers containing carboxyl groups;

[0013] 10-20 parts of antibacterial monomers containing quaternary ammonium salt groups;

[0014] 5-10 parts of biodegradable monomers containing ester bonds.

[0015] This invention designs the raw materials for preparing vinylpyrrolidone copolymers. By using a combination of specific amounts of N-vinylpyrrolidone, hydrophilic monomers containing carboxyl groups, antibacterial monomers containing quaternary ammonium salt groups, and biodegradable monomers containing ester bonds, the resulting vinylpyrrolidone copolymers can possess excellent biocompatibility, antibacterial properties, and biodegradability.

[0016] Furthermore, when the content of antibacterial monomers containing quaternary ammonium salt groups is too low, the antibacterial properties of the resulting vinylpyrrolidone copolymers are insufficient. When the content is too high, the antibacterial properties of the resulting vinylpyrrolidone copolymers no longer increase significantly, but instead the proportion of other monomers decreases accordingly, thereby affecting the structure of the resulting vinylpyrrolidone copolymers and their compatibility with other drugs. This leads to a decrease in the degradation performance of the vinylpyrrolidone copolymers, and the increased content increases production costs and reduces economic benefits.

[0017] The weight parts of N-vinylpyrrolidone in the raw materials for preparing vinylpyrrolidone copolymers provided by the present invention can be 30 parts, 32 parts, 35 parts, 38 parts, 40 parts, 42 parts, 45 parts, 48 ​​parts or 50 parts, as well as specific values ​​between the above points. Due to space limitations and for the sake of brevity, the present invention will not exhaustively list the specific values ​​included in the range.

[0018] The weight percentage of the hydrophilic monomer containing a carboxyl group in the raw materials for preparing the vinylpyrrolidone copolymers provided by this invention can be 10 parts, 11 parts, 12 parts, 13 parts, 14 parts, 15 parts, 16 parts, 17 parts, 18 parts, 19 parts, or 20 parts, as well as specific values ​​between the above-mentioned values. Due to space limitations and for the sake of brevity, this invention will not exhaustively list the specific values ​​included in the range.

[0019] The weight percentage of the antibacterial monomer containing quaternary ammonium salt groups in the raw materials for preparing the vinylpyrrolidone copolymers provided by the present invention can be 10 parts, 11 parts, 12 parts, 13 parts, 14 parts, 15 parts, 16 parts, 17 parts, 18 parts, 19 parts, or 20 parts, as well as specific values ​​between the above-mentioned values. Due to space limitations and for the sake of brevity, the present invention will not exhaustively list the specific values ​​included in the range.

[0020] The weight percentage of the biodegradable monomer containing ester bonds in the raw materials for preparing the vinylpyrrolidone copolymers provided by this invention can be 5 parts, 5.5 parts, 6 parts, 6.5 parts, 7 parts, 7.5 parts, 8 parts, 8.5 parts, 9 parts, 9.5 parts, or 10 parts, as well as specific values ​​between the above-mentioned values. Due to space limitations and for the sake of brevity, this invention will not exhaustively list the specific values ​​included in the range.

[0021] Preferably, the carboxyl-containing hydrophilic monomer includes acrylic acid and / or methacrylic acid monomers.

[0022] Preferably, the antibacterial monomer containing quaternary ammonium salt groups includes any one or a combination of at least two of dimethyl diallyl ammonium chloride, diethyl diallyl ammonium chloride, allyl trimethyl ammonium chloride, acryloyloxyethyl trimethyl ammonium chloride, or methacryloyloxyethyl trimethyl ammonium chloride.

[0023] Preferably, the ester-containing biodegradable monomer includes polyethylene glycol diacrylate (PEGDA).

[0024] Preferably, the weight average molecular weight of the ester-containing biodegradable monomer is 200-400, for example, it can be 200, 220, 250, 280, 300, 320, 350, 380 or 400, as well as specific values ​​between the above values. Due to space limitations and for the sake of brevity, the present invention will not exhaustively list the specific values ​​included in the range.

[0025] This invention optimizes the weight-average molecular weight of ester-containing biodegradable monomers, thereby improving the biodegradability of the resulting vinylpyrrolidone copolymers and producing water-soluble multifunctional polymeric materials with excellent degradation performance. When the weight-average molecular weight is low, the end groups are more reactive and prone to side reactions, affecting the structure of the resulting vinylpyrrolidone copolymers and consequently their degradation efficiency. Furthermore, the purification of ester-containing biodegradable monomers with lower weight-average molecular weights is more difficult. Conversely, when the weight-average molecular weight is high, the activity of the biodegradable monomers is lower, resulting in fewer monomers copolymerized onto the vinylpyrrolidone molecules and a poorer degradation effect.

[0026] Preferably, the raw materials for preparing the vinylpyrrolidone copolymer also include an initiator.

[0027] Preferably, the initiator in the raw materials for preparing the vinylpyrrolidone copolymer is 0.2-2 parts by weight, for example, 0.2 parts, 0.5 parts, 0.8 parts, 1 part, 1.2 parts, 1.5 parts, 1.8 parts or 2 parts, and specific values ​​between the above points. Due to space limitations and for the sake of brevity, the present invention will not exhaustively list the specific values ​​included in the range.

[0028] Preferably, the initiator includes persulfate initiators and / or azo initiators.

[0029] Preferably, the persulfate initiator includes ammonium persulfate and / or potassium persulfate.

[0030] Preferably, the azo initiator includes azobisisobutyram hydrochloride (V-50), azobisisobutyramidazoline hydrochloride (VA-044), or azobisisobutyramic acid metal salt.

[0031] Preferably, the azobis(4-cyanopentarate) metal salt comprises 4,4'-azobis(4-cyanopentarate sodium salt).

[0032] Preferably, the raw materials for preparing the vinylpyrrolidone copolymer further include a solvent, wherein the solvent includes water. Preferably, the solvent in the raw materials for preparing the vinylpyrrolidone copolymer is 100-200 parts by weight, for example, 100 parts, 110 parts, 120 parts, 130 parts, 140 parts, 150 parts, 160 parts, 170 parts, 180 parts, 190 parts, or 200 parts, as well as specific values ​​between the above values. Due to space limitations and for the sake of brevity, the present invention will not exhaustively list the specific values ​​included in the range.

[0033] In a second aspect, the present invention provides a method for preparing vinylpyrrolidone copolymers as described in the first aspect, the method comprising the following steps:

[0034] The vinylpyrrolidone copolymer is obtained by polymerizing N-vinylpyrrolidone, a hydrophilic monomer containing a carboxyl group, an antibacterial monomer containing a quaternary ammonium salt group, and a biodegradable monomer containing an ester bond.

[0035] Preferably, the polymerization reaction is carried out at a temperature of 70-80°C for 4-6 hours.

[0036] Wherein, 70-80℃ can be 70℃, 71℃, 72℃, 73℃, 74℃, 75℃, 76℃, 77℃, 78℃, 79℃ or 80℃, and 4-6 h can be 4 h, 4.2 h, 4.5 h, 4.8 h, 5 h, 5.2 h, 5.5 h, 5.8 h or 6 h, as well as specific point values ​​between the above point values. Due to space limitations and for the sake of brevity, this invention will not exhaustively list the specific point values ​​included in the range.

[0037] Preferably, the polymerization reaction is carried out in a solvent, which includes water.

[0038] Preferably, the polymerization reaction is carried out in a protective gas atmosphere, the protective gas including any one or a combination of at least two of nitrogen, argon or helium.

[0039] Preferably, the polymerization reaction is carried out under an initiator, which includes persulfate initiators and / or azo initiators.

[0040] Preferably, the temperature of the system before the initiator is added is 60-65°C, for example, it can be 60°C, 61°C, 62°C, 63°C, 64°C or 65°C, as well as specific values ​​between the above points. Due to space limitations and for the sake of brevity, the present invention will not exhaustively list the specific values ​​included in the range.

[0041] Preferably, the initiator is added in batches.

[0042] It should be noted that the batch-addition method of the initiator in this invention can effectively eliminate residues, not only accelerating the reaction rate of the monomer but also making the polymerization reaction more thorough and complete. Furthermore, in this invention, to ensure faster and more uniform mixing of the added initiator with the reaction solution, the initiator can be dissolved in a small amount of solvent to prepare a solution (exemplarily including but not limited to 0.1 g of initiator pre-dissolved in 1 g of solvent) before being added to the reaction system.

[0043] Preferably, a polymeric liquid is obtained after the polymerization reaction is completed.

[0044] Preferably, the mass percentage of N-vinylpyrrolidone in the polymer solution is <0.1%, for example, it can be 0.01%, 0.02%, 0.03%, 0.04%, 0.05%, 0.06%, 0.07%, 0.08%, or 0.09%, as well as specific values ​​between the above values. Due to space limitations and for the sake of brevity, the present invention will not exhaustively list the specific values ​​included in the range.

[0045] It should be noted that the mass percentage of N-vinylpyrrolidone in the polymer polymerization liquid of the present invention is detected by liquid chromatography to detect the degree of completion of the polymerization reaction. When the mass percentage of N-vinylpyrrolidone is less than 0.1%, the polymerization reaction is considered to be complete.

[0046] Preferably, the polymerization reaction further includes a post-processing step.

[0047] Preferably, the post-processing method includes dialysis of the polymer solution through a dialysis bag followed by drying.

[0048] Preferably, the molecular weight cutoff of the dialysis bag is 10,000 Da.

[0049] In this invention, by using dialysis bags for dialysis, unreacted monomers and impurities in the preparation of vinylpyrrolidone copolymers can be removed, thereby improving the purity of the product.

[0050] It should be noted that there is no special limitation on the dialysis time in this invention, and it can be adjusted according to the actual situation, including but not limited to dialysis for 48-84 hours.

[0051] Preferably, the drying method includes freeze drying.

[0052] Specifically, the preparation method of the vinylpyrrolidone copolymer includes the following steps:

[0053] N-vinylpyrrolidone (NVP), a hydrophilic monomer containing a carboxyl group, an antibacterial monomer containing a quaternary ammonium salt group, and a biodegradable monomer containing an ester bond are mixed with a solvent and heated to 60-65°C under a protective gas atmosphere. An initiator is added and the temperature is controlled at 70-80°C for 4-6 hours to obtain a polymeric polymer solution. The polymeric polymer solution is dialyzed through a dialysis bag (molecular weight cutoff 10000 Da) and then freeze-dried to obtain the vinylpyrrolidone copolymer.

[0054] The method for preparing vinylpyrrolidone copolymers provided by this invention uses aqueous phase polymerization, which effectively avoids organic solvent pollution, and the reaction system is green, efficient, economical and environmentally friendly.

[0055] Thirdly, the present invention provides a water-soluble multifunctional polymer material, wherein the raw materials for preparing the water-soluble multifunctional polymer material include a targeting monomer and a vinylpyrrolidone copolymer as described in the first aspect.

[0056] Preferably, the mass ratio of the targeting monomer to the water-soluble polymer copolymer is (1-1.5):1, wherein (1-1.5) can be, for example, 1, 1.05, 1.1, 1.15, 1.2, 1.25, 1.3, 1.35, 1.4, 1.45 or 1.5, and specific values ​​between the above values. Due to space limitations and for the sake of brevity, the present invention will not exhaustively list the specific values ​​included in the range.

[0057] This invention designs the content of each raw material component in the preparation raw materials of vinylpyrrolidone copolymers, and then adjusts the mass ratio of vinylpyrrolidone copolymers to target monomers. This enables the customization of degradation rate, antibacterial activity and targeting, thus making the resulting water-soluble multifunctional polymer material suitable for different medical scenarios (such as short-term dressings and long-term drug carriers), with strong practicality.

[0058] Preferably, the targeting monomer comprises aminophenylboronic acid or aminophenylboronic ester.

[0059] Fourthly, the present invention provides a method for preparing a water-soluble multifunctional polymer material as described in the third aspect, the method comprising the following steps:

[0060] The water-soluble multifunctional polymer material is obtained by amidation reaction of the target monomer with a vinylpyrrolidone copolymer.

[0061] It should be noted that, in this invention, if the target monomer is aminophenylboronic acid, in order to avoid the generation of byproducts due to the instability of the boric acid group, it is necessary to protect the boric acid group in aminophenylboronic acid before carrying out the amidation reaction. There are no special limitations on the method of protecting the boric acid group in aminophenylboronic acid, and exemplary methods include but are not limited to: using pinacol to carry out an esterification reaction with aminophenylboronic acid to form a cyclic pinacol ester.

[0062] Preferably, the temperature of the amidation reaction is 30-40°C, for example, it can be 30°C, 31°C, 32°C, 33°C, 34°C, 35°C, 36°C, 37°C, 38°C, 39°C or 40°C, as well as specific values ​​between the above points. Due to space limitations and for the sake of brevity, the present invention will not exhaustively list the specific values ​​included in the range.

[0063] Preferably, the amidation reaction time is 2-3 h, for example, it can be 2 h, 2.1 h, 2.2 h, 2.3 h, 2.4 h, 2.5 h, 2.6 h, 2.7 h, 2.8 h, 2.9 h or 3 h, as well as specific values ​​between the above points. Due to space limitations and for the sake of brevity, the present invention will not exhaustively list the specific values ​​included in the range.

[0064] Preferably, the pH of the amidation reaction system is 5.5-6, for example, it can be 5.5, 5.6, 5.7, 5.8, 5.9 or 6, as well as specific values ​​between the above values. Due to space limitations and for the sake of brevity, the present invention will not exhaustively list the specific values ​​included in the range.

[0065] Preferably, the amidation reaction is carried out in a medium.

[0066] Preferably, the medium comprises water.

[0067] Preferably, the amidation reaction is followed by an ester hydrolysis reaction.

[0068] In this invention, the boronic acid groups of aminophenylboronic ester are removed by hydrolysis through an ester hydrolysis reaction, thereby giving the resulting water-soluble multifunctional polymer material excellent targeting properties.

[0069] Preferably, the ester hydrolysis reaction is carried out in an acidic system with a pH of 4.0-4.5.

[0070] It should be noted that the acidic system of this invention refers to adjusting the pH of the system after the amidation reaction to 4.0-4.5 using an acid solution. There are no specific limitations on the choice of acid solution in this invention, but exemplary examples include, but are not limited to, a 0.1 mol / L dilute hydrochloric acid solution.

[0071] Preferably, the ester hydrolysis reaction takes 6-8 hours.

[0072] Preferably, the ester hydrolysis reaction further includes a post-treatment step.

[0073] Preferably, the post-treatment method after the ester hydrolysis reaction includes dialysis and drying.

[0074] Preferably, the dialysis is performed in a dialysis bag, and the molecular weight cutoff of the dialysis bag is 10,000 Da.

[0075] In this invention, unreacted monomers and impurities from the preparation of water-soluble multifunctional polymer materials can be removed by using dialysis bags.

[0076] Preferably, the drying method includes freeze drying.

[0077] Specifically, the preparation method of the water-soluble multifunctional polymer material includes:

[0078] After mixing vinylpyrrolidone copolymers, targeting monomers, and media, the reaction was carried out at 30-40℃ with the pH adjusted to 5.5-6 for 2-3 h. The pH was then adjusted to 4.0-4.5 and stirring was continued for 6-8 h. Afterward, the mixture was dialyzed through a dialysis bag (molecular weight cutoff of 10000 Da) and freeze-dried to obtain the water-soluble multifunctional polymer material.

[0079] Fifthly, the present invention provides the application of the water-soluble multifunctional polymer material as described in the third aspect in the preparation of medical dressings, drug carriers, biosensor coatings, or cell culture scaffolds.

[0080] Compared with the prior art, the present invention has at least the following beneficial effects:

[0081] (1) The raw materials for preparing vinylpyrrolidone copolymers provided by the present invention use NVP as the core monomer. By combining it with hydrophilic monomers containing carboxyl groups, antibacterial monomers containing quaternary ammonium salt groups, and degradable monomers containing ester bonds, the molecular structure of vinylpyrrolidone copolymers is designed, thereby breaking through the single-function limitation of traditional vinylpyrrolidone copolymers. Biocompatibility (NVP, acrylic acid), antibacterial properties (quaternary ammonium salts) and controllable degradation (ester monomers) are integrated into the same molecular structure, solving the multi-dimensional needs of medical materials or daily chemical products, and effectively expanding the application boundaries of NVP-based polymers.

[0082] (2) Furthermore, the present invention utilizes carboxyl groups for molecular modification, thereby effectively introducing the target monomer into vinylpyrrolidone copolymers to form a water-soluble multifunctional polymer material that possesses excellent biocompatibility, controllable degradation (degradation rate of 7-46%), high-efficiency antibacterial properties (antibacterial rate ≥62%), and drug loading capacity. Through further optimization of specific polymer monomers and their contents, the resulting water-soluble multifunctional polymer material can achieve an antibacterial rate of ≥76%, up to 99% or more, and a degradation rate of ≥40%, thereby enabling the water-soluble multifunctional polymer material to be well applied in fields such as medical dressings, drug carriers, biosensor coatings, and cell culture scaffolds. Detailed Implementation

[0083] To facilitate understanding of the present invention, the following embodiments are provided. Those skilled in the art should understand that these embodiments are merely illustrative and should not be construed as limiting the scope of the invention.

[0084] Unless otherwise specified, the materials and equipment involved in the following detailed embodiments are all conventional materials and equipment in the art and will not affect the technical effects of the present invention.

[0085] Unless otherwise specified, all reagents and raw materials used in the following examples and comparative examples are commercially available products. Some raw material information is as follows:

[0086] Polyethylene glycol diacrylate A (PEGDA-200), polyethylene glycol diacrylate B (PEGDA-400) and polyethylene glycol diacrylate C (PEGDA-600) were all purchased from Aladdin.

[0087] Example 1

[0088] This embodiment provides a vinylpyrrolidone copolymer and its preparation method, the preparation method comprising the following steps:

[0089] 40 g of N-vinylpyrrolidone (NVP), 20 g of acrylic acid, 20 g of methacryloyloxyethyltrimethylammonium chloride, 10 g of polyethylene glycol diacrylate A, and 150 g of deionized water were mixed and heated to 60°C in a water bath under nitrogen protection. 0.5 g of initiator V-50 (dissolved in 5 g of deionized water) was added, and the reaction was carried out for 60 min. The temperature was then maintained at 75°C for 4 h. During this period, 0.1 g of V-50 was added every 1 h to carry out the residue elimination reaction until the NVP residue was less than 0.1%. After cooling, a polymer solution was obtained. The polymer solution was dialyzed through a dialysis bag (molecular weight cutoff 10000 Da) for 72 h and then freeze-dried to obtain a white flocculent vinylpyrrolidone copolymer.

[0090] Example 2

[0091] This embodiment provides a vinylpyrrolidone copolymer and its preparation method, the preparation method comprising the following steps:

[0092] 30 g of N-vinylpyrrolidone (NVP), 20 g of acrylic acid, 15 g of methacryloyloxyethyltrimethylammonium chloride, 5 g of polyethylene glycol diacrylate A, and 100 g of deionized water were mixed and heated to 62 °C in a water bath under nitrogen protection. 0.5 g of potassium persulfate (dissolved in 5 g of deionized water) was added as an initiator. After reacting for 60 min, the temperature was controlled at 70 °C and maintained for 5 h. During this period, 0.1 g of potassium persulfate was added every 1 h to carry out the residue elimination reaction until the NVP residue was less than 0.1%. After cooling, a polymer solution was obtained. The polymer solution was dialyzed through a dialysis bag (molecular weight cutoff 10000 Da) for 72 h and then freeze-dried to obtain a white flocculent vinylpyrrolidone copolymer.

[0093] Example 3

[0094] This embodiment provides a vinylpyrrolidone copolymer and its preparation method, the preparation method comprising the following steps:

[0095] 35 g of N-vinylpyrrolidone (NVP), 15 g of acrylic acid, 10 g of N,N-dimethylallylammonium chloride, 10 g of polyethylene glycol diacrylate A, and 150 g of deionized water were mixed and heated to 60°C in a water bath under nitrogen protection. 0.1 g of initiator V-50 (dissolved in 1 g of deionized water) was added, and the mixture was reacted for 60 min. The temperature was then maintained at 75°C for 4 h, with 0.05 g of V-50 added every h to eliminate residual NVP until the NVP residue was below 0.1%. After cooling, a polymer solution was obtained. The polymer solution was dialyzed through a dialysis bag (molecular weight cutoff 10000 Da) for 72 h and then freeze-dried to obtain a white flocculent vinylpyrrolidone copolymer.

[0096] Example 4

[0097] This embodiment provides a vinylpyrrolidone copolymer and its preparation method, the preparation method comprising the following steps:

[0098] 50 g of N-vinylpyrrolidone (NVP), 10 g of methacrylic acid, 20 g of methacryloyloxyethyltrimethylammonium chloride, 8 g of polyethylene glycol diacrylate A, and 200 g of deionized water were mixed and heated to 65°C in a water bath under nitrogen protection. 0.8 g of initiator V-044 (dissolved in 8 g of deionized water) was added, and the mixture was reacted for 60 min. The temperature was then maintained at 75°C for 6 h, with 0.2 g of V-044 added every 1 h to eliminate residual NVP until the NVP residue was less than 0.1%. After cooling, a polymer solution was obtained. The polymer solution was dialyzed through a dialysis bag (molecular weight cutoff 10000 Da) for 72 h and then freeze-dried to obtain a white flocculent vinylpyrrolidone copolymer.

[0099] Example 5

[0100] This embodiment provides a vinylpyrrolidone copolymer and its preparation method. The only difference between this embodiment and Example 1 is that polyethylene glycol diacrylate A in Example 1 is replaced with an equal mass of polyethylene glycol diacrylate. All other raw materials, contents, and preparation methods are the same as in Example 1.

[0101] Example 6

[0102] This embodiment provides a vinylpyrrolidone copolymer and its preparation method. The only difference between this embodiment and Example 1 is that polyethylene glycol diacrylate A in Example 1 is replaced with an equal mass of polyethylene glycol diacrylate B. All other raw materials, contents, and preparation methods are the same as in Example 1.

[0103] Example 7

[0104] This embodiment provides a vinylpyrrolidone copolymer and its preparation method. The only difference between this embodiment and Example 1 is that polyethylene glycol diacrylate A in Example 1 is replaced with an equal mass of polyethylene glycol diacrylate C. All other raw materials, contents, and preparation methods are the same as in Example 1.

[0105] Example 8

[0106] This embodiment provides a vinylpyrrolidone copolymer and its preparation method. The only difference between this embodiment and Example 1 is that the content of methacryloyloxyethyltrimethylammonium chloride in Example 1 is adjusted from 20 g to 8 g. All other raw materials, contents and preparation methods are the same as in Example 1.

[0107] Example 9

[0108] This embodiment provides a vinylpyrrolidone copolymer and its preparation method. The only difference between this embodiment and Example 1 is that the content of methacryloyloxyethyltrimethylammonium chloride in Example 1 is adjusted from 20 g to 10 g. All other raw materials, contents and preparation methods are the same as in Example 1.

[0109] Example 10

[0110] This embodiment provides a vinylpyrrolidone copolymer and its preparation method. The only difference between this embodiment and Example 1 is that the content of methacryloyloxyethyltrimethylammonium chloride in Example 1 is adjusted from 20 g to 15 g. All other raw materials, contents and preparation methods are the same as in Example 1.

[0111] Example 11

[0112] This embodiment provides a vinylpyrrolidone copolymer and its preparation method. The only difference between this embodiment and Example 1 is that the content of methacryloyloxyethyltrimethylammonium chloride in Example 1 is adjusted from 20 g to 25 g. All other raw materials, contents and preparation methods are the same as in Example 1.

[0113] Comparative Example 1

[0114] This comparative example provides a vinylpyrrolidone copolymer and its preparation method. The only difference between this example and Example 1 is that methacryloyloxyethyltrimethylammonium chloride is not added in Example 1. All other raw materials, contents and preparation methods are the same as in Example 1.

[0115] Comparative Example 2

[0116] This comparative example provides a vinylpyrrolidone copolymer and its preparation method. The only difference between this example and Example 1 is that polyethylene glycol diacrylate A is not added in Example 1. All other raw materials, contents and preparation methods are the same as in Example 1.

[0117] Application Example 1

[0118] This application example provides a water-soluble multifunctional polymer material and its preparation method, the preparation method comprising the following steps:

[0119] 100 g of vinylpyrrolidone copolymer (Example 1), 120 g of pinacol 3-aminophenylboronic acid, and 500 g of deionized water were mixed and reacted at 35°C to adjust the pH to 5.8 for 2.5 h. Then, 0.1 mol / L dilute hydrochloric acid solution was added to adjust the pH to 4.3 and stirring was continued for 7 h. After that, the mixture was dialyzed through a dialysis bag (molecular weight cutoff 10000 Da) and freeze-dried to obtain the water-soluble multifunctional polymer material.

[0120] Application Example 2

[0121] This application example provides a water-soluble multifunctional polymer material and its preparation method, the preparation method comprising the following steps:

[0122] 100 g of vinylpyrrolidone copolymer (Example 2), 130 g of pinacol 4-aminophenylboronic acid, and 500 g of deionized water were mixed and reacted at 30°C to adjust the pH to 5.5 for 2.2 h. Then, 0.1 mol / L dilute hydrochloric acid solution was added to adjust the pH to 4.0 and stirring was continued for 6 h. After that, the mixture was dialyzed through a dialysis bag (molecular weight cutoff 10000 Da) and freeze-dried to obtain the water-soluble multifunctional polymer material.

[0123] Application Example 3

[0124] This application example provides a water-soluble multifunctional polymer material and its preparation method, the preparation method comprising the following steps:

[0125] 100 g of vinylpyrrolidone copolymer (Example 3), 100 g of pinacol 3-aminophenylboronic acid, and 500 g of deionized water were mixed and reacted at 35°C to adjust the pH to 5.8 for 2.5 h. Then, 0.1 mol / L dilute hydrochloric acid solution was added to adjust the pH to 4.3 and stirring was continued for 7 h. After that, the mixture was dialyzed through a dialysis bag (molecular weight cutoff 10000 Da) and freeze-dried to obtain the water-soluble multifunctional polymer material.

[0126] Application Example 4

[0127] This application example provides a water-soluble multifunctional polymer material and its preparation method, the preparation method comprising the following steps:

[0128] 100 g of vinylpyrrolidone copolymer (Example 4), 150 g of pinacol 3-aminophenylboronic acid, and 500 g of deionized water were mixed and reacted at 40°C to adjust the pH to 6.0 for 3 h. Then, 0.1 mol / L dilute hydrochloric acid solution was added to adjust the pH to 4.5 and stirring was continued for 8 h. After that, the mixture was dialyzed through a dialysis bag (molecular weight cutoff 10000 Da) and freeze-dried to obtain the water-soluble multifunctional polymer material.

[0129] Application Example 5-11 and Comparative Application Example 1-2

[0130] This application example provides a water-soluble multifunctional polymer material and its preparation method. The only difference between this application example and application example 1 is that the vinylpyrrolidone copolymer (Example 1) in application example 1 is replaced with an equal mass of vinylpyrrolidone copolymer (Examples 5-11, Comparative Examples 1-2). All other raw materials, contents and preparation methods are the same as in application example 1.

[0131] The performance of the water-soluble multifunctional polymer materials provided in corresponding use case 1-11 and comparative application example 1-2 was tested using the following methods / standards:

[0132] (1) Antibacterial performance: In accordance with GB / T 21510-2008 standard, water-soluble multifunctional polymer materials were co-cultured with bacterial solution, and the antibacterial rate was calculated by counting the number of surviving colonies and comparing with the blank group; the bacteria used for testing were Escherichia coli, purchased from Shanghai Zeye Biotechnology ZY-39500.

[0133] (2) Degradability: Referring to GB / T 16886.13-2022 standard, phosphate buffered saline (PBS) with pH 7.4 was used as the simulated body fluid. 10 mg of water-soluble multifunctional polymer material was placed in 50 mL of simulated body fluid and cultured at 37℃ and 50 r / min. After 30 days, the sample was taken out and freeze-dried to constant weight. The degradation rate was calculated by the formula "degradation rate = (initial mass - degraded mass) / initial mass × 100%".

[0134] The test results are shown in Table 1.

[0135] Table 1

[0136]

[0137] According to the test results in Table 1:

[0138] (1) As can be seen from Application Examples 1 to 11, the water-soluble multifunctional polymer material obtained by molecular modification of the vinylpyrrolidone copolymer provided by the present invention after carboxyl group modification can have excellent biocompatibility, controllable degradation, high efficiency antibacterial and drug loading capacity, with an antibacterial rate of ≥62% and a degradation rate of 17-46%.

[0139] (2) A comparison of Application Example 1 with Application Examples 5-7 shows that when the molecular weight of the biodegradable monomer containing ester bonds is low (Application Example 5) and high (Application Example 7), the degradation rate of the obtained water-soluble multifunctional polymer material is significantly reduced. This indicates that by optimizing the molecular weight of the biodegradable monomer containing ester bonds, the present invention can further improve the biodegradability of the obtained water-soluble multifunctional polymer material. Furthermore, a comparison of Application Examples 1-11 with Comparative Application Example 2 shows that when no biodegradable monomer containing ester bonds is added, the degradation performance of the obtained water-soluble multifunctional polymer material is poor, with a degradation rate of only 13.4%.

[0140] (3) By comparing Application Example 1 with Application Examples 8-11, it can be seen that when the content of antibacterial monomers containing quaternary ammonium salt groups is low (Application Example 8), the antibacterial rate of the obtained water-soluble multifunctional polymer material decreases and the antibacterial performance deteriorates. When the content of antibacterial monomers containing quaternary ammonium salt groups is high (Application Example 11), the antibacterial rate of the obtained water-soluble multifunctional polymer material decreases. That is, within a certain range, even if the content of antibacterial monomers containing quaternary ammonium salt groups is increased, the antibacterial performance of the obtained water-soluble multifunctional polymer material no longer improves. Instead, the structure of the obtained vinylpyrrolidone copolymer is affected by the decrease in the proportion of other monomers, resulting in a slight decrease in its degradation rate. This shows that the present invention can further improve the antibacterial performance of the obtained water-soluble multifunctional polymer material by controlling the content of antibacterial monomers containing quaternary ammonium salt groups. Furthermore, by comparing Application Examples 1-11 with Comparative Application Example 1, it can be seen that when no antibacterial monomer containing quaternary ammonium salt groups is added, the antibacterial performance of the resulting water-soluble multifunctional polymer material is poor, with an antibacterial rate of only 15.0%, which means that a good antibacterial effect cannot be achieved.

[0141] In summary, this invention uses NVP as the core monomer and copolymerizes it with a carboxyl-containing hydrophilic monomer and a quaternary ammonium salt-containing antibacterial monomer to form a vinylpyrrolidone copolymer. After molecular modification with carboxyl groups, the resulting water-soluble multifunctional polymer material possesses excellent biocompatibility, controllable degradation, high-efficiency antibacterial properties, and drug loading capacity. Furthermore, by selecting specific polymerizing monomers and their contents, the resulting water-soluble multifunctional polymer material can achieve an antibacterial rate ≥76%, reaching up to 99%, and a degradation rate ≥40%.

[0142] The above description is only a specific embodiment of the present invention, but the protection scope of the present invention is not limited thereto. Those skilled in the art should understand that any changes or substitutions that can be easily conceived by those skilled in the art within the technical scope disclosed in the present invention fall within the protection and disclosure scope of the present invention.

Claims

1. A vinylpyrrolidone copolymer, characterized in that, The raw materials for preparing the vinylpyrrolidone copolymers include N-vinylpyrrolidone, hydrophilic monomers containing carboxyl groups, antibacterial monomers containing quaternary ammonium salt groups, and biodegradable monomers containing ester bonds.

2. The vinylpyrrolidone copolymer according to claim 1, characterized in that, The raw materials for preparing the vinylpyrrolidone copolymer include the following components in parts by weight: 30-50 parts of N-vinylpyrrolidone; 10-20 parts of hydrophilic monomers containing carboxyl groups; 10-20 parts of antibacterial monomers containing quaternary ammonium salt groups; 5-10 parts of biodegradable monomers containing ester bonds.

3. The vinylpyrrolidone copolymer according to claim 1 or 2, characterized in that, The carboxyl-containing hydrophilic monomers include acrylic acid and / or methacrylic acid monomers; The antibacterial monomer containing quaternary ammonium salt groups includes any one or a combination of at least two of dimethyl diallyl ammonium chloride, diethyl diallyl ammonium chloride, allyl trimethyl ammonium chloride, acryloyloxyethyl trimethyl ammonium chloride, or methacryloyloxyethyl trimethyl ammonium chloride. The ester-containing biodegradable monomers include polyethylene glycol diacrylate; The weight-average molecular weight of the ester-containing biodegradable monomer is 200-400.

4. The vinylpyrrolidone copolymer according to claim 1 or 2, characterized in that, The raw materials for preparing the vinylpyrrolidone copolymer also include an initiator; The initiator in the raw materials for preparing the vinylpyrrolidone copolymer is 0.2-2 parts by weight; The initiator includes persulfate initiators and / or azo initiators; The persulfate initiator includes ammonium persulfate and / or potassium persulfate; The azo initiators include azobisisobutyram hydrochloride, azobisisobutyramidazole hydrochloride, or azobisisobutyramidazole metal salt; The raw materials for preparing the vinylpyrrolidone copolymer also include a solvent, which includes water; The solvent in the raw materials for preparing the vinylpyrrolidone copolymer is 100-200 parts by weight.

5. A method for preparing a vinylpyrrolidone copolymer as described in any one of claims 1-4, characterized in that, The preparation method includes the following steps: The vinylpyrrolidone copolymer is obtained by polymerizing N-vinylpyrrolidone, a hydrophilic monomer containing a carboxyl group, an antibacterial monomer containing a quaternary ammonium salt group, and a biodegradable monomer containing an ester bond.

6. The method for preparing vinylpyrrolidone copolymers according to claim 5, characterized in that, The polymerization reaction is carried out at a temperature of 70-80℃ for 4-6 hours. The polymerization reaction is carried out in a solvent, including water; The polymerization reaction is carried out in a protective gas atmosphere, which includes any one or a combination of at least two of nitrogen, argon or helium; The polymerization reaction is carried out under the initiator, which includes persulfate initiators and / or azo initiators; The temperature of the system before the initiator is added is 60-65℃, and the initiator is added in batches. After the polymerization reaction is completed, a polymeric polymer solution is obtained, wherein the mass percentage of N-vinylpyrrolidone in the polymeric polymer solution is <0.1%; The polymerization reaction is completed and a post-processing step is also included. The post-processing method includes dialysis of the polymer solution through a dialysis bag followed by drying. The molecular weight cutoff of the dialysis bag is 10,000 Da.

7. A water-soluble multifunctional polymer material, characterized in that, The raw materials for preparing the water-soluble multifunctional polymer material include a targeting monomer and a vinylpyrrolidone copolymer as described in any one of claims 1-4.

8. The water-soluble multifunctional polymer material according to claim 7, characterized in that, The mass ratio of the target monomer to the water-soluble polymer copolymer is (1-1.5):1; The targeting monomer includes aminophenylboronic acid or aminophenylboronic ester.

9. A method for preparing a water-soluble multifunctional polymer material as described in claim 7 or 8, characterized in that, The preparation method includes the following steps: The target monomer is subjected to an amidation reaction with a vinylpyrrolidone copolymer to obtain the water-soluble multifunctional polymer material. The amidation reaction is carried out at a temperature of 30-40℃ for 2-3 hours. The pH of the system for the amidation reaction is 5.5-6; The amidation reaction is carried out in a medium, which includes water; The amidation reaction is followed by an ester hydrolysis reaction step; The ester hydrolysis reaction is carried out in an acidic system with a pH of 4.0-4.

5. The ester hydrolysis reaction takes 6-8 hours; The ester hydrolysis reaction is followed by a post-treatment step, which includes dialysis and drying.

10. The application of the water-soluble multifunctional polymer material as described in claim 7 or 8 in the preparation of medical dressings, drug carriers, biosensor coatings, or cell culture scaffolds.

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