Interpenetrating network polymers based on phosphorylcholine polymers, methods of making and use thereof

Abstract

The application belongs to the technical field of medical biomaterials, and particularly relates to an interpenetrating network polymer based on phosphorylcholine polymer and a preparation method and application thereof. The application provides a sequential interpenetrating network method, which comprises the following steps: preparing a monomer infiltration solution containing phosphorylcholine monomer, polyethylene glycol methacrylate, dimethylaminoethyl methacrylate, butyl methacrylate, hydroxyethyl methacrylate, ethylene glycol methacrylate, a crosslinking agent and an initiator; dipping a high-molecular polymer matrix into the monomer infiltration solution, and performing ultrasonic oscillation treatment to promote the infiltration of monomers into the interior of the matrix; and performing a polymerization reaction to obtain a final product after washing; the material prepared by the application has excellent thermal stability, excellent swelling performance, intelligent pH response drug release capacity and biocompatibility, and is suitable for the fields of biological medicine and cosmetics.

Description

Technical Field

[0001] This invention belongs to the field of medical biomaterials technology, specifically relating to interpenetrating polymer networks based on phosphorylcholine polymers, their preparation methods, and applications. Background Technology

[0002] In the field of biomedical engineering, developing materials that can mimic the characteristics of natural tissues and possess excellent biocompatibility is key to achieving efficient wound repair and targeted therapy. Interpenetrating polymer networks (IPNs) are considered ideal candidate materials due to their three-dimensional network structure, high water content, and tunable physicochemical properties. IPNs consist of two or more cross-linked but interpenetrating polymer networks, which can combine the advantages of each component to achieve synergistic and enhanced performance, resulting in materials with excellent mechanical properties and biological functions.

[0003] Among numerous bioactive polymers, phosphorylcholine polymers have attracted much attention due to their side-chain structure being similar to key components of the cell membrane phospholipid bilayer. These biomimetic materials can effectively resist non-specific protein adsorption and platelet adhesion through their zwitterionic structure, exhibiting excellent blood compatibility and antifouling ability, and have been widely studied for use in anticoagulant coatings, drug carriers, etc.

[0004] Existing single-component or simple blend hydrogels still have significant limitations in medical applications. While pure phosphorylcholine polymers have excellent biocompatibility, they often lack cell-specific recognition sites, which is not conducive to tissue integration and regeneration. Although natural collagen can promote cell adhesion, its mechanical properties are poor and it is prone to rapid degradation in physiological environments. If the two are simply physically blended, phase separation problems are often encountered, resulting in unstable material structures. Traditional cross-linking strategies may have biotoxicity, and the resulting network structures are static and rigid, unable to respond to changes in the microenvironment of the lesion site, making it difficult to achieve on-demand and precise drug release.

[0005] Therefore, there is a need in this field for a new technical solution that can combine the antifouling and biocompatibility of phosphorylcholine polymers with the cell-promoting function of natural macromolecular polymers, and endow the material with dynamic and intelligent responsive properties, so as to overcome the defects of existing materials and meet the needs of high-end biomedical materials. Summary of the Invention

[0006] One of the objectives of this invention is to provide a method for preparing interpenetrating polymer networks based on phosphorylcholine polymers, in order to solve the aforementioned technical problems. To achieve the above-mentioned technical objectives, the technical solution of the present invention is as follows: The method for preparing interpenetrating polymer networks based on phosphorylcholine polymers includes the following steps: S1. The suitable monomer and crosslinking agent are dissolved in deionized water, stirred evenly, and inert gas is introduced to remove oxygen. Ammonium persulfate is added and stirred evenly to obtain monomer permeate. S2. The polymer matrix is ​​immersed in the monomer permeation solution and treated at 10-45℃ for 5-20 min under ultrasonic oscillation conditions at a frequency of 10-55 kHz and a power density of 0.1-0.5 W / cm² to obtain a swollen polymer matrix. The swollen polymer matrix is ​​removed, excess liquid is wiped off the surface, and it is left to stand at 35-65℃ for 2-8 h under an inert atmosphere. S3. After the reaction is complete, the polymer is washed with PBS buffer and deionized water in sequence to obtain an interpenetrating network polymer based on phosphorylcholine polymer.

[0007] As a further improvement, the adaptor monomer is phosphorylcholine monomer, polyethylene glycol methacrylate, dimethylaminoethyl methacrylate, butyl methacrylate, hydroxyethyl methacrylate, and ethylene glycol methacrylate, and the crosslinking agent is N,N-methylenebisacrylamide.

[0008] As a further improvement, the polymer matrix is ​​selected from one of the following: modified collagen polymers, hyaluronic acid polymers, cellulose and its derivatives, cyclodextrin and its derivatives, organosilicon polymers, waterborne polyurethane polymers, and polyvinylpyrrolidone polymers.

[0009] As a further improvement, the phosphorylcholine monomer is at least one selected from methacryloyloxyethyl phosphorylcholine, acryloyloxyethyl phosphorylcholine, methacryloyloxypropyl phosphorylcholine, 4-(methacryloyloxy)butyl phosphorylcholine, 6-(methacryloyloxy)hexyl phosphorylcholine, and vinyl phosphorylcholine.

[0010] As a further improvement, the molar ratio of polyethylene glycol methacrylate, phosphorylcholine monomer, dimethylaminoethyl methacrylate, butyl methacrylate, hydroxyethyl methacrylate, and ethylene glycol methacrylate is 2~4:1~3:1~3:0.5~2:0.5~2:0.5~2; the molar amount of ammonium persulfate is 1.0%~1.5% of the total molar amount of the six components: polyethylene glycol methacrylate, phosphorylcholine monomer, dimethylaminoethyl methacrylate, butyl methacrylate, hydroxyethyl methacrylate, and ethylene glycol methacrylate; the number average molecular weight of the polyethylene glycol methacrylate is 200~1000 g / mol; and the molar amount of N,N-methylenebisacrylamide is 0.5%~2% of the total molar amount of the six components: polyethylene glycol methacrylate, phosphorylcholine monomer, dimethylaminoethyl methacrylate, butyl methacrylate, hydroxyethyl methacrylate, and ethylene glycol methacrylate.

[0011] As a further improvement, the polymer matrix is ​​a modified collagen polymer; the preparation method of the modified collagen polymer is as follows: collagen is dissolved in a 0.1% (v / v) acetic acid solution, cooled in an ice bath, and sodium bicarbonate buffer is slowly added dropwise to adjust the pH to 7.5-8.0 while continuously stirring to obtain a collagen solution; citric anhydride is dissolved in DMSO, slowly added to the collagen solution while continuously stirring, and the pH is adjusted to 7.9-8.1 using sodium hydroxide solution, reacted at 4°C for 2-4 h, the reaction solution is dialyzed with 0.1% acetic acid solution for 48 h, dialyzed with deionized water for 24 h, and freeze-dried to obtain modified collagen; the modified collagen is dissolved in a pH 7.4 Tris-HCl buffer, stirred and mixed to prepare a 5-10 mg / mL collagen solution, MTG enzyme is added, mixed evenly, poured into a mold, incubated at 30-37°C for 2-4 h, and washed with PBS to obtain the modified collagen polymer.

[0012] As a further improvement, the molar ratio of collagen to citric anhydride is 1:10~20; the collagen is type I collagen.

[0013] As a further improvement, the amount of MTG enzyme added is 10~15 U / g modified collagen.

[0014] Another object of the present invention is to provide an interpenetrating network polymer based on phosphorylcholine polymer prepared by the aforementioned preparation method.

[0015] Another object of the present invention is to provide the application of phosphorylcholine-based interpenetrating network polymers in the fields of biomedicine and cosmetics.

[0016] Due to the adoption of the above technical solution, the beneficial effects of the present invention are as follows: 1. The interpenetrating polymer network based on phosphorylcholine polymer prepared in this invention has excellent biocompatibility and intelligent drug release capability, combining cell membrane-mimicking phosphorylcholine polymer with a variety of functionally tunable polymer matrices. This invention introduces polyethylene glycol methacrylate (PEGMA), which synergistically resists non-specific protein adsorption with phosphorylcholine monomers. By introducing dimethylaminoethyl methacrylate (DMAEMA), the interpenetrating polymer network exhibits excellent pH response characteristics. Further introduction of butyl methacrylate (BMA), hydroxyethyl methacrylate (HEMA), and ethylene glycol methacrylate (EGMA) respectively endows the material with tunable hydrophobic and hydrophilic balance, enhanced hydrophilic water retention properties, and a denser antifouling interface, thereby synergistically improving the material's mechanical strength, drug loading capacity, and cell compatibility, significantly improving therapeutic efficacy, safety, and targeting, and the performance can be flexibly customized according to the target application.

[0017] 2. The interpenetrating network polymer based on phosphorylcholine polymer prepared in this invention has a stable three-dimensional interpenetrating structure. The core advantage of the sequential interpenetrating network preparation method is that it can achieve uniform penetration and in-situ polymerization of monomers within a variety of preset solid polymer matrices, thereby constructing a topologically entangled and structurally stable three-dimensional interpenetrating network. By controlling the crosslinking density, the intrinsic properties of the matrix, and the ratio of the two in a wide range and with precision, the diverse performance requirements of materials in different application scenarios can be met. Attached Figure Description

[0018] Figure 1 This is an ATR-FTIR result image of the modified collagen prepared in Example 1; Figure 2 This is the ATR-FTIR result of the crosslinked copolymer prepared in Comparative Example 4; Figure 3 This is a SEM scan image of the interpenetrating network polymer based on phosphorylcholine polymer prepared in Example 1; Figure 4 The graph shows the experimental results of water absorption swelling rate of the final product samples of Example 1 and Comparative Examples 1-5; Figure 5 This is a graph showing the pH-responsive drug release kinetics results of the final product samples from Example 1 and Comparative Example 2. Detailed Implementation

[0019] The technical solution of the present invention will be clearly and completely described below with reference to specific embodiments. However, those skilled in the art will understand that the embodiments described below are some embodiments of the present invention, but not all embodiments, and are only used to illustrate the present invention, and should not be regarded as limiting the scope of the present invention. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention. Where specific conditions are not specified in the embodiments, conventional conditions or manufacturer's conditions shall be followed. Where the manufacturers of reagents or instruments are not specified, they are all conventional products that can be purchased commercially.

[0020] Example 1: Preparation method of interpenetrating polymer network based on phosphorylcholine polymer. The specific preparation process is as follows: S1. Preparation of modified collagen polymer: Weigh 2.0 g of type I collagen (average molecular weight 285 kDa), dissolve it in 100 mL of pre-cooled 0.1% (v / v) acetic acid solution, stir slowly at 4 °C until dissolved, place in an ice-water bath, and add sodium bicarbonate buffer solution (pH 9.0) dropwise with slow stirring to adjust the pH to 8.0, obtaining a collagen solution; Separately, weigh 70.17 μmol of citric anhydride, dissolve it in 5 mL of dimethyl sulfoxide (DMSO), and slowly add the citric anhydride solution dropwise to the above collagen solution with continuous stirring in an ice-water bath. After the addition is complete, adjust the pH to 8.1 using sodium hydroxide solution, and react at 4 °C. After 4 hours of reaction, the reaction solution was transferred to a dialysis bag with a molecular weight cutoff of 8000-14000 Da. It was dialyzed with 0.1% acetic acid solution for 48 hours, followed by dialysis with deionized water for 24 hours. The dialyzed solution was freeze-dried to obtain modified collagen. The modified collagen was dissolved in Tris-HCl buffer at pH 7.4, stirred and mixed to prepare a 5 mg / mL collagen solution. MTG enzyme (transglutaminase) was added at a concentration of 10 U / g modified collagen. After mixing evenly, the solution was poured into a mold and incubated at 30°C for 2 hours. The solution was washed three times with PBS to obtain the modified collagen polymer. The reaction equation for collagen and citric anhydride is shown below: ; The ATR-FTIR results of the modified collagen prepared in this embodiment are shown in the figure below. Figure 1 As shown.

[0021] S2. Accurately weigh 12 mmol of polyethylene glycol methacrylate (PEGMA, Mn=200 g / mol), 8 mmol of methacryloyloxyethyl phosphorylcholine (MPC), 8 mmol of dimethylaminoethyl methacrylate (DMAEMA), 4 mmol of butyl methacrylate (BMA), 4 mmol of hydroxyethyl methacrylate (HEMA), 4 mmol of ethylene glycol methacrylate (EGMA), and 0.2 mmol of N,N-methylenebisacrylamide. Dissolve them in a three-necked flask containing 100 mL of deionized water. Stir for 15 min to make it homogeneous, and then pass in an inert gas to remove oxygen for 30 min. Add 0.4 mmol of ammonium persulfate as an initiator and stir for 5 min to obtain the monomer permeate. S3. The modified collagen polymer was immersed in the monomer permeation solution and treated at 30°C for 10 min under ultrasonic oscillation at a frequency of 20 kHz and a power density of 0.1 W / cm² to obtain a swollen polymer matrix. The swollen polymer matrix was removed, excess liquid was wiped off the surface, and it was allowed to stand at 65°C for 4 h under an inert atmosphere. After the reaction was completed, it was washed three times with PBS buffer and deionized water to obtain an interpenetrating network polymer based on phosphorylcholine polymer.

[0022] Example 2: Preparation method of interpenetrating polymer network based on phosphorylcholine polymer. The specific preparation process is as follows: S1. Preparation of modified collagen polymer: Weigh 2.0 g of type I collagen (average molecular weight 285 kDa), dissolve it in 100 mL of pre-cooled 0.1% (v / v) acetic acid solution, stir slowly at 4 °C until dissolved, place in an ice-water bath, and add sodium bicarbonate buffer solution (pH 9.0) dropwise with slow stirring to adjust the pH to 7.5, obtaining a collagen solution; Separately, weigh 140.34 μmol of citric anhydride, dissolve it in 5 mL of dimethyl sulfoxide (DMSO), and slowly add the citric anhydride solution dropwise to the above collagen solution with continuous stirring in an ice-water bath. After the addition is complete, adjust the pH to 7.9 using sodium hydroxide solution. The reaction was carried out at 4℃ for 2 hours. After the reaction, the reaction solution was transferred to a dialysis bag with a molecular weight cutoff of 8000~14000 Da. The solution was dialyzed with 0.1% acetic acid solution for 48 hours and then dialyzed with deionized water for 24 hours. The dialyzed solution was freeze-dried to obtain modified collagen. The modified collagen was dissolved in Tris-HCl buffer at pH 7.4, stirred and mixed to prepare a collagen solution of 10 mg / mL. MTG enzyme was added at a concentration of 15 U / g modified collagen. After mixing evenly, the solution was poured into a mold and incubated at 37℃ for 4 hours. The solution was washed twice with PBS to obtain the modified collagen polymer. S2. Accurately weigh 20 mmol of polyethylene glycol methacrylate (PEGMA, Mn=1000 g / mol), 10 mmol of methacryloyloxyethyl phosphorylcholine (MPC), 10 mmol of dimethylaminoethyl methacrylate (DMAEMA), 5 mmol of butyl methacrylate (BMA), 5 mmol of hydroxyethyl methacrylate (HEMA), 5 mmol of ethylene glycol methacrylate (EGMA), and 1.1 mmol of N,N-methylenebisacrylamide. Dissolve them in a three-necked flask containing 100 mL of deionized water. Stir for 15 min to make it homogeneous. Purge with inert gas to remove oxygen for 30 min. Add 0.825 mmol of ammonium persulfate as an initiator and stir for 5 min to obtain the monomer permeate. S3. The modified collagen polymer was immersed in the monomer permeation solution and treated at 15°C for 15 min under ultrasonic oscillation at a frequency of 40 kHz and a power density of 0.5 W / cm² to obtain a swollen polymer matrix. The swollen polymer matrix was removed, excess liquid was wiped off the surface, and it was allowed to stand at 50°C for 6 h under an inert atmosphere. After the reaction was completed, it was washed three times with PBS buffer and deionized water to obtain an interpenetrating polymer network based on phosphorylcholine polymer.

[0023] Example 3: Preparation method of interpenetrating polymer network based on phosphorylcholine polymer. The specific preparation process is as follows: S1. Dissolve 12 mmol of polyethylene glycol methacrylate, 9 mmol of acryloyloxyethyl phosphorylcholine, 9 mmol of dimethylaminoethyl methacrylate, 6 mmol of butyl methacrylate, 6 mmol of hydroxyethyl methacrylate, 6 mmol of ethylene glycol methacrylate, and 0.48 mmol of N,N-methylenebisacrylamide in a three-necked flask containing 100 mL of deionized water. Stir for 15 min to make it homogeneous, and then purge with inert gas to remove oxygen for 30 min. Add 0.48 mmol of ammonium persulfate as an initiator and stir for 5 min to obtain the monomer permeate. S2. The aqueous polyurethane polymer was immersed in the monomer permeate solution and treated at 30°C for 20 min under ultrasonic oscillation at a frequency of 20 kHz and a power density of 0.1 W / cm² to obtain a swollen polymer matrix. The swollen polymer matrix was removed, excess liquid was wiped off the surface, and it was allowed to stand at 65°C for 2 h under an inert atmosphere. After the reaction was completed, it was washed three times with PBS buffer and deionized water to obtain an interpenetrating polymer network based on phosphorylcholine polymer.

[0024] Example 4: Preparation method of interpenetrating polymer network based on phosphorylcholine polymer. The specific preparation process is as follows: S1. Dissolve 20 mmol of polyethylene glycol methacrylate, 10 mmol of methacryloyloxypropylphosphonic choline, 10 mmol of dimethylaminoethyl methacrylate, 10 mmol of butyl methacrylate, 10 mmol of hydroxyethyl methacrylate, 10 mmol of ethylene glycol methacrylate, and 0.70 mmol of N,N-methylenebisacrylamide in a three-necked flask containing 100 mL of deionized water. Stir for 15 min to make it homogeneous, and then purge with inert gas to remove oxygen for 30 min. Add 0.875 mmol of ammonium persulfate as an initiator, stir for 5 min, and obtain the monomer permeate. S2. The hyaluronic acid polymer was immersed in the monomer permeation solution and treated at 10°C for 20 min under ultrasonic oscillation at a frequency of 55 kHz and a power density of 0.3 W / cm² to obtain a swollen polymer matrix. The swollen polymer matrix was removed, excess liquid was wiped off the surface, and it was allowed to stand at 65°C for 4 h under an inert atmosphere. After the reaction was completed, it was washed three times with PBS buffer and deionized water to obtain an interpenetrating network polymer based on phosphorylcholine polymer.

[0025] Example 5: Preparation method of interpenetrating polymer network based on phosphorylcholine polymer. The specific preparation process is as follows: S1. Dissolve 20 mmol of polyethylene glycol methacrylate, 10 mmol of vinyl phosphorylcholine, 10 mmol of dimethylaminoethyl methacrylate, 10 mmol of butyl methacrylate, 20 mmol of hydroxyethyl methacrylate, 20 mmol of ethylene glycol methacrylate, and 0.90 mmol of N,N-methylenebisacrylamide in a three-necked flask containing 100 mL of deionized water. Stir for 15 min to make it homogeneous, and then purge with inert gas to remove oxygen for 30 min. Add 0.90 mmol of ammonium persulfate as an initiator and stir for 5 min to obtain the monomer permeate. S2. The cellulose derivative, namely sodium carboxymethyl cellulose hydrogel, was immersed in the monomer permeate and treated at 35°C for 10 min under ultrasonic oscillation at a frequency of 20 kHz and a power density of 0.2 W / cm² to obtain a swollen polymer matrix. The swollen polymer matrix was removed, excess liquid was wiped off the surface, and it was allowed to stand at 65°C for 6 h under an inert atmosphere. After the reaction was completed, it was washed three times with PBS buffer and deionized water to obtain an interpenetrating polymer network based on phosphorylcholine polymer.

[0026] Example 6: Preparation method of interpenetrating polymer network based on phosphorylcholine polymer. The specific preparation process is as follows: S1. Dissolve 20 mmol of polyethylene glycol methacrylate, 10 mmol of methacryloyloxyethyl phosphorylcholine, 10 mmol of dimethylaminoethyl methacrylate, 20 mmol of butyl methacrylate, 10 mmol of hydroxyethyl methacrylate, 20 mmol of ethylene glycol methacrylate, and 0.90 mmol of N,N-methylenebisacrylamide in a three-necked flask containing 100 mL of deionized water. Stir for 15 min to make it homogeneous, and then purge with inert gas to remove oxygen for 30 min. Add 0.90 mmol of ammonium persulfate as an initiator and stir for 5 min to obtain the monomer permeate. S2. The cyclodextrin derivative, namely the hydroxypropyl-β-cyclodextrin inclusion complex membrane, was immersed in the monomer permeate and treated at 40°C for 10 min under ultrasonic oscillation at a frequency of 45 kHz and a power density of 0.4 W / cm² to obtain a swollen polymer matrix. The swollen polymer matrix was removed, excess liquid was wiped off the surface, and it was allowed to stand at 55°C for 4 h under an inert atmosphere. After the reaction was completed, it was washed three times with PBS buffer and deionized water to obtain an interpenetrating polymer network based on phosphorylcholine polymer.

[0027] Example 7: Preparation method of interpenetrating polymer network based on phosphorylcholine polymer. The specific preparation process is as follows: S1. Dissolve 20 mmol of polyethylene glycol methacrylate, 10 mmol of methacryloyloxyethyl phosphorylcholine, 10 mmol of dimethylaminoethyl methacrylate, 20 mmol of butyl methacrylate, 20 mmol of hydroxyethyl methacrylate, 10 mmol of ethylene glycol methacrylate, and 0.45 mmol of N,N-methylenebisacrylamide in a three-necked flask containing 100 mL of deionized water. Stir for 15 min to make it homogeneous, and then purge with an inert gas to remove oxygen for 30 min. Add 0.90 mmol of ammonium persulfate as an initiator and stir for 5 min to obtain the monomer permeate. S2. After hydrophilic pretreatment of the organosilicon polymer, namely polydimethylsiloxane elastomer, it is immersed in monomer permeation solution and treated at 30℃ for 10 min under ultrasonic oscillation conditions at a frequency of 50 kHz and a power density of 0.4 W / cm² to obtain a swollen polymer matrix. The swollen polymer matrix is ​​taken out, excess liquid on the surface is wiped off, and it is allowed to stand at 60℃ for 4 h under an inert atmosphere. After the reaction is completed, it is washed three times with PBS buffer and deionized water to obtain an interpenetrating network polymer based on phosphorylcholine polymer.

[0028] Example 8: Preparation method of interpenetrating polymer network based on phosphorylcholine polymer. The specific preparation process is as follows: S1. Dissolve 10 mmol of 4-(methacryloyloxy)butylphosphocholine, 20 mmol of polyethylene glycol methacrylate, 10 mmol of dimethylaminoethyl methacrylate, 10 mmol of butyl methacrylate, 10 mmol of hydroxyethyl methacrylate, 10 mmol of ethylene glycol methacrylate, and 0.70 mmol of N,N-methylenebisacrylamide in a three-necked flask containing 100 mL of deionized water. Stir for 15 min to make it homogeneous, and then purge with inert gas to remove oxygen for 30 min. Add 0.875 mmol of ammonium persulfate as an initiator and stir for 5 min to obtain the monomer permeate. S2. The polyvinylpyrrolidone polymer was immersed in the monomer permeation solution and treated at 45°C for 5 min under ultrasonic oscillation at a frequency of 10 kHz and a power density of 0.5 W / cm² to obtain a swollen polymer matrix. The swollen polymer matrix was removed, excess liquid was wiped off the surface, and it was allowed to stand at 35°C for 8 h under an inert atmosphere. After the reaction was completed, it was washed three times with PBS buffer and deionized water to obtain an interpenetrating polymer network based on phosphorylcholine polymer.

[0029] Comparative Example 1: The preparation method of the interpenetrating polymer network based on phosphorylcholine polymer differs from Example 1 in that PEGMA was not used. The specific preparation process is as follows: S1. Preparation of modified collagen polymer: Weigh 2.0 g of type I collagen (average molecular weight 285 kDa), dissolve it in 100 mL of pre-cooled 0.1% (v / v) acetic acid solution, stir slowly at 4 °C until dissolved, place in an ice-water bath, and add sodium bicarbonate buffer solution (pH 9.0) dropwise with slow stirring to adjust the pH to 8.0, obtaining a collagen solution; Separately, weigh 70.17 μmol of citric anhydride, dissolve it in 5 mL of dimethyl sulfoxide (DMSO), and slowly add the citric anhydride solution dropwise to the above collagen solution with continuous stirring in an ice-water bath. After the addition is complete, adjust the pH to 8.1 using sodium hydroxide solution. The reaction was carried out at 4℃ for 4 hours. After the reaction, the reaction solution was transferred to a dialysis bag with a molecular weight cutoff of 8000~14000 Da. The solution was dialyzed with 0.1% acetic acid solution for 48 hours and then dialyzed with deionized water for 24 hours. The dialyzed solution was freeze-dried to obtain modified collagen. The modified collagen was dissolved in Tris-HCl buffer at pH 7.4, stirred and mixed to prepare a collagen solution of 5 mg / mL. MTG enzyme was added at a concentration of 10 U / g modified collagen. After mixing evenly, the solution was poured into a mold and incubated at 30℃ for 4 hours. The solution was washed three times with PBS to obtain the modified collagen polymer. S2. Accurately weigh 8 mmol of methacryloyloxyethyl phosphorylcholine (MPC), 8 mmol of dimethylaminoethyl methacrylate (DMAEMA), 4 mmol of butyl methacrylate (BMA), 4 mmol of hydroxyethyl methacrylate (HEMA), 4 mmol of ethylene glycol methacrylate (EGMA), and 0.14 mmol of N,N-methylenebisacrylamide. Dissolve them in a three-necked flask containing 100 mL of deionized water. Stir for 15 min to make it homogeneous, and then pass in an inert gas to remove oxygen for 30 min. Add 0.28 mmol of ammonium persulfate as an initiator, stir for 5 min, and obtain the monomer permeate. S3. The modified collagen polymer was immersed in the monomer permeation solution and treated at 30°C for 10 min under ultrasonic oscillation at a frequency of 20 kHz and a power density of 0.1 W / cm² to obtain a swollen polymer matrix. The swollen polymer matrix was removed, excess liquid was wiped off the surface, and it was allowed to stand at 65°C for 4 h under an inert atmosphere. After the reaction was completed, it was washed three times with PBS buffer and deionized water to obtain an interpenetrating network polymer based on phosphorylcholine polymer.

[0030] Comparative Example 2 describes the preparation method of an interpenetrating polymer network based on phosphorylcholine polymers. The difference from Example 1 is that DMAEMA was not used. The specific preparation process is as follows: S1. Preparation of modified collagen polymer: Weigh 2.0 g of type I collagen (average molecular weight 285 kDa), dissolve it in 100 mL of pre-cooled 0.1% (v / v) acetic acid solution, stir slowly at 4 °C until dissolved, place in an ice-water bath, and add sodium bicarbonate buffer solution (pH 9.0) dropwise with slow stirring to adjust the pH to 8.0, obtaining a collagen solution; Separately, weigh 70.17 μmol of citric anhydride, dissolve it in 5 mL of dimethyl sulfoxide (DMSO), and slowly add the citric anhydride solution dropwise to the above collagen solution with continuous stirring in an ice-water bath. After the addition is complete, adjust the pH to 8.1 using sodium hydroxide solution. The reaction was carried out at 4℃ for 4 hours. After the reaction, the reaction solution was transferred to a dialysis bag with a molecular weight cutoff of 8000~14000 Da. The solution was dialyzed with 0.1% acetic acid solution for 48 hours and then dialyzed with deionized water for 24 hours. The dialyzed solution was freeze-dried to obtain modified collagen. The modified collagen was dissolved in Tris-HCl buffer at pH 7.4, stirred and mixed to prepare a collagen solution of 5 mg / mL. MTG enzyme was added at a concentration of 10 U / g modified collagen. After mixing evenly, the solution was poured into a mold and incubated at 30℃ for 4 hours. The solution was washed three times with PBS to obtain the modified collagen polymer. S2. Accurately weigh 12 mmol of polyethylene glycol methacrylate (PEGMA, Mn=200 g / mol), 8 mmol of methacryloxyethyl phosphorylcholine (MPC), 4 mmol of butyl methacrylate (BMA), 4 mmol of hydroxyethyl methacrylate (HEMA), 4 mmol of ethylene glycol methacrylate (EGMA), and 0.16 mmol of N,N-methylenebisacrylamide. Dissolve them in a three-necked flask containing 100 mL of deionized water. Stir for 15 min to make it homogeneous, and then pass in an inert gas to remove oxygen for 30 min. Add 0.32 mmol of ammonium persulfate as an initiator and stir for 5 min to obtain the monomer permeate. S3. The modified collagen polymer was immersed in the monomer permeation solution and treated at 30°C for 10 min under ultrasonic oscillation at a frequency of 20 kHz and a power density of 0.1 W / cm² to obtain a swollen polymer matrix. The swollen polymer matrix was removed, excess liquid was wiped off the surface, and it was allowed to stand at 65°C for 4 h under an inert atmosphere. After the reaction was completed, it was washed three times with PBS buffer and deionized water to obtain an interpenetrating network polymer based on phosphorylcholine polymer.

[0031] Comparative Example 3: The preparation method of the interpenetrating polymer network based on phosphorylcholine polymer differs from that of Example 1 in that step S3 does not involve ultrasonic oscillation. The specific preparation process is as follows: S1. Preparation of modified collagen polymer: Weigh 2.0 g of type I collagen (average molecular weight 285 kDa), dissolve it in 100 mL of pre-cooled 0.1% (v / v) acetic acid solution, stir slowly at 4 °C until dissolved, place in an ice-water bath, and add sodium bicarbonate buffer solution (pH 9.0) dropwise with slow stirring to adjust the pH to 8.0, obtaining a collagen solution; Separately, weigh 70.17 μmol of citric anhydride, dissolve it in 5 mL of dimethyl sulfoxide (DMSO), and slowly add the citric anhydride solution dropwise to the above collagen solution with continuous stirring in an ice-water bath. After the addition is complete, adjust the pH to 8.1 using sodium hydroxide solution. The reaction was carried out at 4℃ for 4 hours. After the reaction, the reaction solution was transferred to a dialysis bag with a molecular weight cutoff of 8000~14000 Da. The solution was dialyzed with 0.1% acetic acid solution for 48 hours and then dialyzed with deionized water for 24 hours. The dialyzed solution was freeze-dried to obtain modified collagen. The modified collagen was dissolved in Tris-HCl buffer at pH 7.4, stirred and mixed to prepare a collagen solution of 5 mg / mL. MTG enzyme was added at a concentration of 10 U / g modified collagen. After mixing evenly, the solution was poured into a mold and incubated at 30℃ for 4 hours. The solution was washed three times with PBS to obtain the modified collagen polymer. S2. Accurately weigh 12 mmol of polyethylene glycol methacrylate (PEGMA, Mn=200 g / mol), 8 mmol of methacryloyloxyethyl phosphorylcholine (MPC), 8 mmol of dimethylaminoethyl methacrylate (DMAEMA), 4 mmol of butyl methacrylate (BMA), 4 mmol of hydroxyethyl methacrylate (HEMA), 4 mmol of ethylene glycol methacrylate (EGMA), and 0.2 mmol of N,N-methylenebisacrylamide. Dissolve them in a three-necked flask containing 100 mL of deionized water. Stir for 15 min to make it homogeneous, and then pass in an inert gas to remove oxygen for 30 min. Add 0.4 mmol of ammonium persulfate as an initiator and stir for 5 min to obtain the monomer permeate. S3. The modified collagen polymer is immersed in the monomer permeation solution for 30 min to obtain a swollen polymer matrix. The swollen polymer matrix is ​​removed, excess liquid is wiped off the surface, and it is left to stand at 65°C for 4 h under an inert atmosphere. After the reaction is completed, it is washed three times with PBS buffer and deionized water to obtain an interpenetrating network polymer based on phosphorylcholine polymer.

[0032] Comparative Example 4 describes a method for preparing an interpenetrating polymer network based on phosphorylcholine polymers. The difference from Example 1 is that only polyethylene glycol methacrylate (PEGMA), methacryloyloxyethyl phosphorylcholine (MPC), dimethylaminoethyl methacrylate (DMAEMA), butyl methacrylate (BMA), hydroxyethyl methacrylate (HEMA), and ethylene glycol methacrylate (EGMA) are used for crosslinking polymerization. The specific preparation process is as follows: Accurately weigh 12 mmol of polyethylene glycol methacrylate (PEGMA, Mn=200 g / mol), 8 mmol of methacryloxyethyl phosphorylcholine (MPC), 8 mmol of dimethylaminoethyl methacrylate (DMAEMA), 4 mmol of butyl methacrylate (BMA), 4 mmol of hydroxyethyl methacrylate (HEMA), 4 mmol of ethylene glycol methacrylate (EGMA), and 0.2 mmol of N,N-methylenebisacrylamide. Dissolve them in a three-necked flask containing 100 mL of deionized water. Stir for 15 min to homogenize, and then purge with an inert gas for 30 min to remove oxygen. Add 0.4 mmol of ammonium persulfate as an initiator, stir for 5 min, and let stand at 65 °C for 4 h under an inert atmosphere. After the reaction is complete, wash three times with PBS buffer and deionized water to obtain the crosslinked copolymer.

[0033] Comparative Example 5 describes a method for preparing an interpenetrating polymer network based on phosphorylcholine polymers. The difference from Example 1 is that it does not contain butyl methacrylate (BMA), hydroxyethyl methacrylate (HEMA), and ethylene glycol methacrylate (EGMA). The specific preparation process is as follows: S1. Preparation of modified collagen polymer: Weigh 2.0 g of type I collagen (average molecular weight 285 kDa), dissolve it in 100 mL of pre-cooled 0.1% (v / v) acetic acid solution, stir slowly at 4 °C until dissolved, place in an ice-water bath, and add sodium bicarbonate buffer solution (pH 9.0) dropwise with slow stirring to adjust the pH to 8.0, obtaining a collagen solution; Separately, weigh 70.17 μmol of citric anhydride, dissolve it in 5 mL of dimethyl sulfoxide (DMSO), and slowly add the citric anhydride solution dropwise to the above collagen solution with continuous stirring in an ice-water bath. After the addition is complete, adjust the pH to 8.1 using sodium hydroxide solution. The reaction was carried out at 4℃ for 4 hours. After the reaction, the reaction solution was transferred to a dialysis bag with a molecular weight cutoff of 8000~14000 Da. The solution was first dialyzed with 0.1% acetic acid solution for 48 hours, and then dialyzed with deionized water for 24 hours. The dialyzed solution was freeze-dried to obtain modified collagen. The modified collagen was dissolved in Tris-HCl buffer at pH 7.4, stirred and mixed to prepare a collagen solution of 5 mg / mL. MTG enzyme was added at a concentration of 10 U / g modified collagen. After mixing evenly, the solution was poured into a mold and incubated at 30℃ for 2 hours. The solution was washed three times with PBS to obtain the modified collagen polymer. S2. Accurately weigh 12 mmol of polyethylene glycol methacrylate (PEGMA, Mn=200 g / mol), 8 mmol of methacryloyloxyethyl phosphorylcholine (MPC), 8 mmol of dimethylaminoethyl methacrylate (DMAEMA), and 0.14 mmol of N,N-methylenebisacrylamide. Dissolve them in a three-necked flask containing 100 mL of deionized water. Stir for 15 min to make it homogeneous, and then pass in an inert gas to remove oxygen for 30 min. Add 0.28 mmol of ammonium persulfate as an initiator and stir for 5 min to obtain the monomer permeate. S3. The modified collagen polymer was immersed in the monomer permeation solution and treated at 30°C for 10 min under ultrasonic oscillation at a frequency of 20 kHz and a power density of 0.1 W / cm² to obtain a swollen polymer matrix. The swollen polymer matrix was removed, excess liquid was wiped off the surface, and it was allowed to stand at 65°C for 4 h under an inert atmosphere. After the reaction was completed, it was washed three times with PBS buffer and deionized water to obtain an interpenetrating network polymer based on phosphorylcholine polymer.

[0034] Performance testing: (1) ATR-FTIR detection The modified collagen prepared in Example 1 and the crosslinked copolymer prepared in Comparative Example 4 were analyzed using attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR).

[0035] The results are as follows Figure 1 and Figure 2 As shown; where, Figure 1 The image shows the ATR-FTIR results of the modified collagen prepared in Example 1. Figure 2 ATR-FTIR image of the crosslinked copolymer prepared in Comparative Example 4; from Figure 1 It can be seen from this that 1600cm -1 The C=O peaks around 1580 cm⁻¹ represent peptide bonds and are characteristic absorption peaks of collagen. -1 The peak represents the asymmetric stretching vibration of the carboxylate group, at 1395 cm⁻¹. -1 These two peaks represent the symmetric vibration peaks of the carboxylate group, and they are key evidence of the successful modification of citric anhydride.

[0036] from Figure 2 It can be seen from this that 1635cm -1 The characteristic peak at 1725 cm⁻¹, indicating the absence of C=C bonds, suggests that all monomers participated in the polymerization reaction; -1 C=O peak, 1085 cm⁻¹ -1 The P=O peak and 1152 cm⁻¹ -1 The COC peak is very obvious; 949 cm⁻¹ -1 The location should be N. + (CH 3 ) 3 The stretching vibration peak at 2800 cm⁻¹ confirmed the existence of MPC; -1 The large peak at that location belongs to the characteristic peaks of CN and CH.

[0037] (2) SEM After drying the sample prepared in Example 1, its cross-section was sputtered with gold, and its microstructure was observed using a scanning electron microscope (SEM).

[0038] The results are as follows Figure 3 As shown, the interpenetrating network polymer prepared in Example 1 exhibits a uniform, continuous and interconnected three-dimensional porous structure with dense pore walls; this indicates that the copolymer network and the collagen network form good interpenetration, thereby producing a significant synergistic structural enhancement effect.

[0039] (3) Thermogravimetric analysis Thermogravimetric analysis was performed on the samples obtained in Examples 1-8 and Comparative Examples 1-5 under a nitrogen atmosphere to examine the thermal stability of the samples. The temperature at which the sample mass loss was 5% was recorded. The experimental results are shown in Table 1. Table 1 Thermogravimetric analysis results of the samples As can be seen from Table 1, the interpenetrating network polymers prepared in Examples 1-8 of the present invention have higher thermal stability than the samples prepared in Comparative Examples 1-5. The above results indicate that the phosphorylcholine copolymer network obtained by the sequential interpenetrating network preparation method described in the present invention forms a stable and compact interpenetrating structure with the modified collagen polymer matrix. In Comparative Example 1, the absence of PEGMA not only affected the hydrophilicity and antifouling properties of the phosphorylcholine network, but also disrupted its synergistic effect with the phosphorylcholine units and the uniformity of network crosslinking, resulting in weakened network structural integrity and reduced thermal stability. In Comparative Example 2, the lack of DMAEMA reduced the thermal stability of the material, indicating that DMAEMA is a key factor in enhancing the bonding force between the two networks and improving the thermal stability of the material. In Comparative Example 3, without ultrasonic assistance, the uniformity of the polymer monomer penetration into the matrix was insufficient, resulting in local defects or incomplete interpenetration in the final interpenetrating network, failing to achieve the optimal structural reinforcement effect, thus affecting thermal stability. Comparative Example 4, using only a single network structure, exhibited the worst thermal stability, indicating that the thermal stability of simple crosslinked copolymers is limited, while the formation of an interpenetrating structure can produce a significant synergistic reinforcement effect. The interpenetrating network greatly improves the thermal stability of the material through molecular-level entanglement and interaction. The thermal stability of Comparative Example 5 was significantly lower than that of the examples, and even lower than that of Comparative Examples 1 and 2, indicating that the introduction of BMA, HEMA, and EGMA was not a simple monomer superposition, but rather significantly improved the structural integrity of the interpenetrating network through synergistic effects.

[0040] (4) Water absorption and swelling The water absorption and swelling rates of Examples 1 and Comparative Examples 1-5 were determined using a gravimetric method. Samples of the same size were used for the experiment, and the initial weight was recorded as W0. These samples were then immersed in physiological saline at pH 7.4 and 37°C. At each preset time point (0.5h, 1h, 2h, 4h, 8h), the samples were removed, the surface moisture was wiped dry with absorbent paper, and the weight was recorded as Wt. Swelling curves were plotted for analysis, and the results are as follows: Figure 4 As shown; by Figure 4 The swelling kinetics curves showed that the swelling equilibrium time for several samples was 4–8 hours. Therefore, we immersed the samples from Examples 1, 3–8, and Comparative Examples 1–5 in PBS at pH 6.0 and pH 7.4 for 8 hours until swelling equilibrium was reached, and then calculated the swelling rate. The formula for calculating the swelling rate is: Swelling rate (%) = (Wt - W0) / W0 × 100%; the experimental results are shown in Table 2. Table 2 Equilibrium swelling ratio of samples at different pH values As can be seen from Table 2, the swelling ratio of the sample in Example 1 at pH 6.0 is significantly higher than that at pH 7.4, indicating that the sample in the example has a clear pH response. The mechanism is the protonation of DMAEMA units under acidic conditions and the resulting enhanced electrostatic repulsion and relaxation of the network structure. The data from Comparative Example 1 show that the hydrophilic segments of PEGMA effectively enhance the hydration capacity of the interpenetrating network, which is the basis for obtaining a suitable swelling rate. The swelling rates of Comparative Example 2 are very low and show no significant difference at different pH levels, proving that DMAEMA is the key to regulating pH-responsive swelling behavior. In Comparative Example 3, without ultrasonic assistance, the monomer permeate cannot diffuse evenly and fully into the interior of the polymer matrix, and a structurally complete and high-performance interpenetrating network polymer cannot be formed, thus failing to fully utilize the pH-responsiveness of DMAEMA. Compared with Comparative Example 4, Example 1 has a higher pH response amplitude, indicating that the interpenetrating network structure can provide stronger swelling performance. The results of Comparative Example 5 show that BMA, HEMA, and EGMA can work synergistically with DMAEMA, making the transformation of the network structure more significant and thorough during pH response, thereby achieving a higher response swelling amplitude.

[0041] (5) Anti-protein adsorption Bovine serum albumin (BSA) was used as a model protein to evaluate the anti-protein adsorption capacity of the samples prepared in Examples 1, 3-8, and Comparative Example 1. 100 mg of each sample was taken and fully swelled and equilibrated using phosphate buffer (pH 7.4). The swollen samples were then transferred to a BSA solution (1.0 mg / mL), with each sample soaked separately. The BSA solution was uniformly 2 mL. The samples were incubated at 37°C with shaking for 2 hours. After incubation, the supernatant was collected, and the concentration of BSA in the solution (C1) was measured using a micro-concentration assay kit (BCA method). The BSA adsorption capacity per unit mass of sample (Q) was calculated using the following formula: Q (μg / mg) = (C0 - C1) * V / M; Where Q represents the amount of BSA adsorbed per unit mass of sample, C0 is the initial concentration of 1.0 mg / mL, C1 is the concentration of BSA after the experiment, V is the volume of the BSA solution of 2.0 mL, and M is the original weight of the gel of 100 mg. The experimental results are shown in Table 3: Table 3 Results of anti-protein adsorption test As can be seen from Table 3, the interpenetrating polymer network prepared by the present invention has excellent anti-protein adsorption capacity. The BSA adsorption amount of Examples 1 and 3-8 is lower than that of Comparative Example 1. This anti-protein adsorption effect is due to the synergistic effect of MPC and PEGMA. The phosphorylcholine group of MPC can form a strong hydration layer through its zwitterionic structure, while the long chain of PEGMA constructs a barrier on the surface through steric hindrance effect and dynamic hydration, thereby greatly blocking the non-specific adsorption of proteins on the surface.

[0042] (6) pH-responsive drug release kinetics Preparation of drug-loaded samples: Doxorubicin hydrochloride (DOX) was used as the test drug for the experiment. The samples prepared in Example 1 and Comparative Example 2 were immersed in a pH 5.5 buffer solution containing doxorubicin hydrochloride at a concentration of 1.0 mg / mL. The samples were incubated at 4°C with gentle shaking in the dark for 12 h. After that, the pH of the drug solution in which the samples were immersed was slowly adjusted to 7.4, and the samples were immersed for another 10 min. After that, the gel was removed and rinsed with phosphate buffer solution at pH 7.4, followed by rinsing with deionized water to remove surface salts and drugs. The drug-loaded samples were then placed at 4°C for later use.

[0043] Take 200 mg of drug-loaded sample, blot dry with filter paper, and immerse in an Erlenmeyer flask containing 50 mL of pH 7.4 PBS. Place in a 37°C constant temperature water bath. At predetermined time points (0.5 h, 1 h, 2 h, 4 h, 8 h), take 3.0 mL of the immersion solution and immediately add 3.0 mL of fresh pH 7.4 PBS at the same temperature. At 8 h, remove all release medium and replace with 50 mL of preheated fresh pH 6.0 PBS. Continue incubation under the same conditions. At predetermined time points (9 h, 10 h, 12 h, 24 h), take immersion solution samples and add an equal volume of fresh pH 6.0 PBS. After appropriate dilution of the samples at each time point, drug concentration is detected using UV-Vis spectrophotometry. The cumulative drug release at each time point is calculated, analyzed, and plotted. The results are shown below. Figure 5 As shown.

[0044] from Figure 5As can be seen, the sample prepared in Example 1 exhibits pH responsiveness, indicating that DMAEMA is the core functional monomer for achieving pH-responsive drug release in the sample of Example 1. The protonation and deprotonation transitions of its tertiary amine group directly regulate the cross-linked network structure, thereby achieving on-demand drug release. In a neutral pH environment, the tertiary amine group of DMAEMA is in a deprotonated state with a strong electron cloud density. At this time, the tertiary amine group forms stable ionic bonds with the carboxyl groups in the modified collagen matrix, which significantly enhances the entanglement between the copolymer network and the collagen matrix network, ultimately forming a dense three-dimensional network structure with high cross-linking density and small pore size. When the ambient pH drops to 6.0, the tertiary amine group of DMAEMA undergoes a protonation reaction, causing it to lose its original electron cloud density. The ionic bonds between it and the carboxyl groups break in large numbers due to charge repulsion. The breaking of ionic bonds directly leads to a weakening of the binding effect of the cross-linked network, a significant reduction in cross-linking density, and a gradual loosening of the originally dense cross-linked network with an enlarged pore size, resulting in a significant reduction in the diffusion resistance of drug molecules.

[0045] The above results indicate that the tertiary amine group of DMAEMA is the key to endowing the material with pH responsiveness. Its protonation state transition under different pH environments directly regulates the crosslinking density and pore size of the interpenetrating network, thereby enabling differential drug release in normal tissues and drug-requiring sites.

[0046] (7) Stability of cosmetics Experimental tests were conducted to determine whether the prepared interpenetrating polymer network, as a functional ingredient, had any impact on the stability of cosmetics after being added to the cosmetic formulation.

[0047] The polymers prepared in Examples 1, 3-8, Comparative Examples 1 and 4 were used in the experiments. The samples were soaked in PBS at pH 7.4 for 1 hour, homogenized, and then prepared into a uniform aqueous dispersion with a solid content of 10%. A representative anti-aging serum was prepared: glycerin (5%), niacinamide (3%), sodium hyaluronate (0.5%), decanoic acid triglyceride (5%), squalane (3%), vitamin E acetate (1%), with the remainder made up with deionized water.

[0048] The blank control group consisted of the aforementioned anti-aging serum. The experimental group consisted of homogeneous aqueous dispersions prepared from samples of Examples 1, 3-8, Comparative Examples 1 and 4, mixed with the aforementioned anti-aging serum and homogenized to prepare test samples with a solid content of 0.5%. All test samples were placed at 25°C and 60% relative humidity. Appearance was observed at the beginning and the third month (observing for layering, precipitation, oil separation, or discoloration under natural light), and pH values ​​were measured. The results are shown in Table 4. Table 4 Results of Cosmetic Stability Tests As shown in Table 4, all samples exhibited a homogeneous emulsion at the initial time point, without any stratification, precipitation, or oil separation, and the pH value was approximately 6.50. After standing for 3 months, the samples in Example 1 still showed a homogeneous emulsion phenomenon, and the pH did not change significantly, indicating that the interpenetrating polymer network of the present invention can be adapted to cosmetic formulation systems and can play a role in physical stabilization. However, the samples in Comparative Example 1 showed slight precipitation after standing for 3 months, indicating that the lack of hydrophilic PEGMA with long-chain spatial stabilizing effect reduced the hydrophilicity of the polymer network and its dispersion stability in the formulation. The samples in Comparative Example 4 showed obvious stratification, indicating that in complex cosmetic emulsion systems, the single network structure cannot form a sufficiently stable support framework, easily aggregates at the oil-water interface, or cannot effectively prevent the fusion of emulsion droplets, leading to complete separation of the oil phase and water phase, thus lacking acid buffering capacity, resulting in the largest overall pH value decrease in the samples.

[0049] Experimental results show that cosmetic formulations containing the interpenetrating network polymer of the present invention exhibit excellent physical stability during long-term storage, good compatibility with cosmetic systems, and can effectively maintain the homogeneity of the system.

[0050] (8) Transdermal absorption of cosmetics Experimental tests were conducted to determine whether the prepared interpenetrating polymer network, as a functional ingredient, had any impact on the transdermal absorption performance of the cosmetics after being added to the cosmetic formulation.

[0051] The polymers prepared in Examples 1-8 were used in the experiments. The samples were soaked in PBS at pH 7.4 for 1 hour, homogenized, and then prepared into a uniform aqueous dispersion with a solid content of 10%. A representative anti-aging serum was prepared: glycerin (5%), niacinamide (3%), sodium hyaluronate (0.5%), decanoic acid triglyceride (5%), squalane (3%), and vitamin E acetate (1%), with the remainder made up with deionized water. The blank control group consisted of the above anti-aging serum, while the experimental group consisted of a mixture of the uniform aqueous dispersion prepared in Example 1 and the above anti-aging serum, homogenized, and then prepared into a test sample with a solid content of 0.5%.

[0052] The transdermal absorption performance of the samples was detected using the Franz vertical diffusion cell method. The test model used was a Strat-M artificial skin membrane. The transdermal capacity of samples from Examples 1-8 and the blank control group was evaluated. The receiving cell was filled with physiological saline containing 30% ethanol as the receiving solution and maintained at a constant temperature of 37°C. 200 mg of samples from Examples 1-8 were evenly applied to the supply cell. After 24 hours, all the receiving solution was collected, and the concentrations of nicotinamide and vitamin E acetate in the receiving solution were measured. The cumulative permeation over 24 hours was recorded. The experimental results are shown in Table 5. Table 5 Results of transdermal absorption detection of cosmetics As can be seen from Table 5, the transdermal absorption performance of the samples in Examples 1-8 was significantly better than that of the blank control group. This result indicates that the interpenetrating network polymers in Examples 1-8 are beneficial to the transdermal absorption of cosmetic ingredients and improve the transdermal efficiency of water-soluble (nicotinamide) and fat-soluble (vitamin E acetate) ingredients. The experimental results prove that adding the interpenetrating network polymers prepared in this invention as functional ingredients to cosmetic formulations can break through the penetration bottleneck of traditional formulations and achieve efficient delivery of active ingredients.

[0053] The specific embodiments of the present invention described above do not constitute a limitation on the scope of protection of the present invention. Any other corresponding changes and modifications made in accordance with the technical concept of the present invention should be included within the scope of protection of the claims of the present invention.

Claims

1. A method for preparing an interpenetrating polymer network based on phosphorylcholine polymers, characterized in that, Includes the following steps: S1. The adaptor monomer and crosslinking agent are dissolved in deionized water, stirred evenly, and an inert gas is introduced to remove oxygen. Ammonium persulfate is added and stirred evenly to obtain a monomer permeate. The adaptor monomer is phosphorylcholine monomer, polyethylene glycol methacrylate, dimethylaminoethyl methacrylate, butyl methacrylate, hydroxyethyl methacrylate, and ethylene glycol methacrylate. S2. The polymer matrix is ​​immersed in a monomer permeation solution and treated at 10-45℃ for 5-20 minutes under ultrasonic oscillation conditions at a frequency of 10-55kHz and a power density of 0.1-0.5W / cm² to obtain a swollen polymer matrix. The swollen polymer matrix is ​​removed, excess liquid is wiped off the surface, and it is left to stand at 35-65℃ for 2-8 hours under an inert atmosphere. The polymer matrix is ​​selected from one of the following: modified collagen polymer, hyaluronic acid polymer, cellulose and its derivatives, cyclodextrin and its derivatives, organosilicon polymer, waterborne polyurethane polymer, and polyvinylpyrrolidone polymer. S3. After the reaction is complete, the polymer is washed with PBS buffer and deionized water in sequence to obtain an interpenetrating network polymer based on phosphorylcholine polymer.

2. The method for preparing the interpenetrating polymer network based on phosphorylcholine polymer according to claim 1, characterized in that, The phosphorylcholine monomer is at least one of methacryloyloxyethyl phosphorylcholine, acryloyloxyethyl phosphorylcholine, methacryloyloxypropyl phosphorylcholine, 4-(methacryloyloxy)butyl phosphorylcholine, 6-(methacryloyloxy)hexyl phosphorylcholine, and vinyl phosphorylcholine.

3. The method for preparing the interpenetrating polymer network based on phosphorylcholine polymer according to claim 1, characterized in that, The molar ratio of polyethylene glycol methacrylate, phosphorylcholine monomer, dimethylaminoethyl methacrylate, butyl methacrylate, hydroxyethyl methacrylate, and ethylene glycol methacrylate is 2~4:1~3:1~3:0.5~2:0.5~2:0.5~2; the molar amount of ammonium persulfate is 1.0%~1.5% of the total molar amount of the six components: polyethylene glycol methacrylate, phosphorylcholine monomer, dimethylaminoethyl methacrylate, butyl methacrylate, hydroxyethyl methacrylate, and ethylene glycol methacrylate; the number average molecular weight of the polyethylene glycol methacrylate is 200~1000 g / mol; and the molar amount of N,N-methylenebisacrylamide is 0.5%~2% of the total molar amount of the six components: polyethylene glycol methacrylate, phosphorylcholine monomer, dimethylaminoethyl methacrylate, butyl methacrylate, hydroxyethyl methacrylate, and ethylene glycol methacrylate.

4. The method for preparing the interpenetrating polymer network based on phosphorylcholine polymer according to claim 1, characterized in that, The polymer matrix is ​​a modified collagen polymer. The modified collagen polymer is prepared as follows: collagen is dissolved in a 0.1% (v / v) acetic acid solution, cooled in an ice bath, and sodium bicarbonate buffer is slowly added dropwise to adjust the pH to 7.5-8.0 while continuously stirring to obtain a collagen solution; citric anhydride is dissolved in DMSO, slowly added to the collagen solution while continuously stirring, and the pH is adjusted to 7.9-8.1 using sodium hydroxide solution. The reaction is carried out at 4°C for 2-4 hours. The reaction solution is dialyzed with 0.1% acetic acid solution for 48 hours, dialyzed with deionized water for 24 hours, and freeze-dried to obtain modified collagen. The modified collagen was dissolved in Tris-HCl buffer at pH 7.4, stirred and mixed to prepare a collagen solution of 5-10 mg / mL. MTG enzyme was added, and the mixture was poured into a mold and incubated at 30-37°C for 2-4 hours. The mixture was then washed with PBS to obtain the modified collagen polymer.

5. The method for preparing the interpenetrating polymer network based on phosphorylcholine polymer according to claim 4, characterized in that, The molar ratio of collagen to citric anhydride is 1:10~20; the collagen is type I collagen.

6. The method for preparing the interpenetrating polymer network based on phosphorylcholine polymer according to claim 4, characterized in that, The amount of MTG enzyme added is 10~15 U / g modified collagen.

7. An interpenetrating polymer network based on phosphorylcholine polymers, characterized in that, The interpenetrating network polymer is prepared by the preparation method according to any one of claims 1 to 6.

8. The application of the phosphorylcholine-based interpenetrating polymer network according to claim 7 in the fields of biomedicine and cosmetics.

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