Hydroxypropyl cellulose grafted poly (3-[N, N-dimethyl-[2-(2-methylpropyl-2-enoyloxy) ethyl] ammonium] propane-1-sulfonic acid inner salt) as well as preparation and application of hydroxypropyl cellulose grafted poly (3-[N, N-dimethyl-[2-(2-methylpropyl-2-enoyloxy) ethyl] ammonium] propane-1-sulfonic acid inner salt)

Abstract

The invention relates to the technical field of medical materials, in particular to hydroxy propyl cellulose grafted poly (3-[N, N-dimethyl-[2-(2-methylpropyl-2-enoyloxy) ethyl] ammonium] propane-1-sulfonic acid inner salt) (HPC-PSBMA) as well as a preparation method and application of the hydroxy propyl cellulose grafted poly (3-[N, N-dimethyl-[2-(2-methylpropyl-2-enoyloxy) ethyl] ammonium] propane-1-sulfonic acid inner salt). The HPC-PSBMA is composed of an HPC main chain and a hydrophilic PSBMA side chain, and when the HPC-PSBMA is used, the HPC-PSBMA is adsorbed to a base material through Van der Waals force of the HPC main chain; the side chain PSBMA contains a large amount of positive and negative charges, and surrounding water molecules can be attracted through electrostatic interaction to form a hydration layer. In addition, the electrostatic interaction between zwitterionic side chains enables HPC-PSBMA to be aggregated, and formation of a lubricating film is facilitated. The factors jointly promote adsorption of HPC-PSBMA molecules on the surface of the medical instrument, so that a stable assembly layer is formed, and the functions of reducing friction and enhancing lubrication are achieved.

Description

Technical Field

[0001] The present invention relates to the technical field of medical materials, and particularly relates to a hydroxypropyl cellulose grafted poly(3-[N,N-dimethyl-[2-(2-methylprop-2-enoyloxy)ethyl]ammonium] propane-1-sulfonate) and its preparation and application. Background Art

[0002] Interventional medical devices are a type of medical tools that enter the body through natural body cavities or surgical incisions to perform diagnostic and therapeutic operations, such as various stents, guide wires, catheters, etc. When such medical devices enter the human body, it is inevitable that there will be contact and relative movement between the surface of the device and soft tissues, and it is very likely that the tissue surface will be damaged due to friction with the device. Reducing the friction on the surface of the device can not only improve the comfort of patients during use, but also effectively prevent the risk of soft tissue damage.

[0003] Applying lubricants on the surface of the device is a common means to reduce friction. Currently, commonly used lubricants include water-soluble lubricants (such as glycerol polyethylene glycol lubricants) and oil-soluble lubricants (such as white oil, paraffin). Oil-soluble lubricants have good film-forming and lubricating properties and can significantly reduce the friction coefficient on the surface of the device, but they have selectivity for the substrate and their application range is limited; for example, white oil will penetrate into medical devices made of silicon-based polymers (such as silicone rubber), destroying the intermolecular forces of silicone rubber, resulting in the hardening and brittleness of the device and affecting the service life of the device. Water-soluble lubricants have relatively stable chemical properties of their components and will not react with substrates such as silicone rubber under normal use conditions, but their adhesion to the substrate is poor, resulting in poor lubricating performance. Summary of the Invention

[0004] In view of this, the purpose of the present invention is to provide a hydroxypropyl cellulose grafted poly(3-[N,N-dimethyl-[2-(2-methylprop-2-enoyloxy)ethyl]ammonium] propane-1-sulfonate) and its preparation and application. The hydroxypropyl cellulose grafted poly(3-[N,N-dimethyl-[2-(2-methylprop-2-enoyloxy)ethyl]ammonium] propane-1-sulfonate) provided by the present invention is water-soluble, has good adhesion to the substrate, can form a complete lubricating film, has good lubricating performance, and at the same time has good biocompatibility.

[0005] In order to achieve the above-mentioned invention purpose, the present invention provides the following technical solutions:

[0006] The present invention provides a hydroxypropyl cellulose grafted poly(3-[N,N-dimethyl-[2-(2-methylprop-2-enoyloxy)ethyl]ammonium] propane-1-sulfonate), which has the structure shown in Formula 1:

[0007]

[0008] In Formula 1, R is -H or -CH2CH(OH)CH3; the ratio of x to y is (0.05 to 0.95):(0.95 to 0.05); m is an integer between 20 and 50.

[0009] The present invention provides a method for preparing the above-mentioned hydroxypropyl cellulose grafted poly(3-[N,N-dimethyl-[2-(2-methylprop-2-enoyloxy)ethyl]ammonium] propane-1-sulfonate inner salt), which comprises the following steps:

[0010] Mix a solution of hydroxypropyl cellulose with a solution of dibromoisobutyryl bromide and carry out an esterification reaction to obtain a hydroxypropyl cellulose bromide initiator; the structural formula of the hydroxypropyl cellulose is as shown in Formula 2, and the structural formula of the hydroxypropyl cellulose bromide initiator is as shown in Formula 3: the mass ratio of the hydroxypropyl cellulose to dibromoisobutyryl bromide is (5000 to 100000):(1 to 5);

[0011]

[0012] In Formulas 2 to 3, R is -H or -CH2CH(OH)CH3;

[0013] Dissolve the hydroxypropyl cellulose bromide initiator, (3-[N,N-dimethyl-[2-(2-methylprop-2-enoyloxy)ethyl]ammonium] propane-1-sulfonate inner salt), copper bromide and an N-containing organic ligand into a polar solvent, and carry out an atom transfer radical polymerization reaction under the protection of an inert gas to obtain the hydroxypropyl cellulose grafted poly(3-[N,N-dimethyl-[2-(2-methylprop-2-enoyloxy)ethyl]ammonium] propane-1-sulfonate inner salt);

[0014] The N-containing organic ligand is tris(2-dimethylaminoethyl)amine or 2,2'-bipyridine;

[0015] The molar ratio of the hydroxypropyl cellulose bromide initiator to (3-[N,N-dimethyl-[2-(2-methylprop-2-enoyloxy)ethyl]ammonium] propane-1-sulfonate inner salt) is (2 to 4):(40 to 60);

[0016] The time of the atom transfer radical polymerization reaction is 10 to 48 h.

[0017] Preferably, the weight average molecular weight of the hydroxypropyl cellulose is 50,000 to 200,000.

[0018] Preferably, the temperature of the esterification reaction is 15 to 35 °C and the time is 6 to 48 h.

[0019] Preferably, the molar ratio of the N-containing organic ligand to copper bromide is (0.8 to 2):(0.5 to 1);

[0020] The mass ratio of the 3-[N,N-dimethyl-[2-(2-methylprop-2-enoyloxy)ethyl]ammonium] propane-1-sulfonate inner salt to cuprous bromide is (40 to 60):(0.5 to 1).

[0021] Preferably, the temperature of the atom transfer radical polymerization reaction is 20 to 35 °C.

[0022] The present invention provides a lubricant solution, comprising the hydroxypropyl cellulose grafted poly(3-[N,N-dimethyl-[2-(2-methylprop-2-enoyloxy)ethyl]ammonium] propane-1-sulfonate inner salt) described in the above solution and an aqueous solvent.

[0023] Preferably, the mass concentration of the hydroxypropyl cellulose grafted poly(3-[N,N-dimethyl-[2-(2-methylprop-2-enoyloxy)ethyl]ammonium] propane-1-sulfonate inner salt) in the lubricant solution is 0.5 to 20 mg / mL.

[0024] Preferably, the aqueous solvent includes water, physiological saline or PBS buffer solution.

[0025] The present invention provides the application of the lubricant solution described in the above solution in reducing friction of medical devices.

[0026] The present invention provides a hydroxypropyl cellulose grafted poly(3-[N,N-dimethyl-[2-(2-methylprop-2-enoyloxy)ethyl]ammonium] propane-1-sulfonate inner salt), abbreviated as HPC-PSBMA. By grafting poly(3-[N,N-dimethyl-[2-(2-methylprop-2-enoyloxy)ethyl]ammonium] propane-1-sulfonate inner salt) (abbreviated as PSBMA) onto hydroxypropyl cellulose (abbreviated as HPC), the non-lubricating HPC is transformed into a water-soluble lubricant.

[0027] In the present invention, the HPC-PSBMA is composed of an HPC main chain and a hydrophilic PSBMA side chain. When in use, the HPC-PSBMA molecules are adsorbed onto the substrate through the van der Waals force of the HPC main chain. At the same time, the PSBMA side chain contains a large number of positive and negative charges, and can attract surrounding water molecules through electrostatic interaction to form a hydration layer. In addition, the electrostatic interaction between the zwitterionic side chains (i.e., the PSBMA side chains) promotes the aggregation of HPC-PSBMA, which is beneficial to the formation of a lubricating film. Under the combined action of these factors, the adsorption of HPC-PSBMA molecules on the surface of medical devices is promoted, thereby forming a stable assembled layer and realizing the functions of reducing friction and enhancing lubrication.

[0028] In addition, the HPC-PSBMA provided by the present invention uses HPC as the main chain and exhibits good biocompatibility. Description of the Drawings

[0029] Figure 1 1H NMR spectra of HPC, HPC-Br, and HPC-PSBMA prepared in Example 1;

[0030] Figure 2 Water solubility test results of HPC, HPC-Br, and HPC-PSBMA;

[0031] Figure 3 Critical micelle concentration test results of HPC-PSBMA solution;

[0032] Figure 4 Atomic force microscopy topography of HPC-PSBMA lubricant solution at different magnifications;

[0033] Figure 5 Fluorescence photograph of HPC-PSBMA film formation on the catheter surface;

[0034] Figure 6 Column comparison chart of the average friction coefficients of HPC-PSBMA lubricant solutions with different concentrations;

[0035] Figure 7 Column comparison chart of the average friction coefficients of the lubricant solutions of Application Example 5, Comparative Example 1, and Comparative Example 2;

[0036] Figure 8 Column comparison chart of the average friction coefficients of the lubricant solutions of Application Example 5, Comparative Example 3, and Comparative Example 4;

[0037] Figure 9 Column comparison chart of the cell survival rates of the HPC-PSBMA lubricant solution of the present invention and the blank control group. Detailed implementation mode

[0038] The present invention provides an HPC-PSBMA having the structure shown in Formula 1:

[0039]

[0040] In Formula 1, R is -H or -CH2CH(OH)CH3.

[0041] In Formula 1, m is an integer between 20 and 50, and in specific embodiments, it can be 20, 25, 30, 35, 40, 45 or 50; the ratio of x to y is (0.05 - 0.95):(0.95 - 0.05), and in specific embodiments, it can be 0.05:0.95, 0.1:0.9, 0.14:0.86, 0.2:0.8, 0.3:0.7, 0.4:0.6, 0.5:0.5, 0.6:0.4, 0.7:0.3, 0.8:0.2, 0.9:0.1 or 0.95:0.05.

[0042] In the present invention, the HPC-PSBMA is composed of an HPC main chain and a hydrophilic PSBMA side chain. When in use, the HPC-PSBMA molecules are adsorbed onto the substrate through the van der Waals force of the HPC main chain. At the same time, the PSBMA side chain contains a large number of positive and negative charges, and can attract surrounding water molecules through electrostatic interaction to form a hydration layer. In addition, the electrostatic interaction between the zwitterionic side chains (i.e., the PSBMA side chains) promotes the aggregation of HPC-PSBMA, which is beneficial to the formation of a lubricating film. Under the combined action of these factors, the adsorption of HPC-PSBMA molecules on the surface of the medical device is promoted, thereby forming a stable assembly layer and realizing the functions of reducing friction and enhancing lubrication.

[0043] The present invention provides a preparation method of the above-mentioned HPC-PSBMA, comprising the following steps:

[0044] Mix a solution of hydroxypropyl cellulose with a solution of dibromoisobutyryl bromide, and carry out an esterification reaction to obtain a hydroxypropyl cellulose bromide initiator;

[0045] Dissolve the hydroxypropyl cellulose bromide initiator, (3-[N,N-dimethyl-[2-(2-methylprop-2-enoyloxy)ethyl]ammonium]propane-1-sulfonate inner salt) (abbreviated as SBMA), copper bromide and an N-containing organic ligand in a polar solvent, and carry out an atom transfer radical polymerization reaction under the protection of an inert gas to obtain the HPC-PSBMA.

[0046] In the present invention, unless otherwise specified, the raw materials used are all well-known commercially available products in the art.

[0047] The present invention mixes a solution of hydroxypropyl cellulose with a solution of dibromoisobutyryl bromide, and carries out an esterification reaction to obtain a hydroxypropyl cellulose bromide initiator.

[0048] In the present invention, the structure of the hydroxypropyl cellulose is as shown in Formula 2:

[0049] In Formula 2, R is -H or -CH2CH(OH)CH3.

[0050] In the present invention, the weight-average molecular weight of the hydroxypropyl cellulose is preferably 50,000 to 200,000, and in specific embodiments, it can be 50,000, 80,000, 100,000, 130,000, 150,000, 170,000 or 200,000.

[0051] In the present invention, the solution of the hydroxypropyl cellulose is preferably obtained by dissolving the hydroxypropyl cellulose in a polar organic solvent; the polar organic solvent is preferably dichloromethane, chloroform, tetrahydrofuran, acetonitrile or toluene; the present invention has no special requirements for the amount of the polar organic solvent, as long as it can dissolve the hydroxypropyl cellulose. In the examples of the present invention, the concentration of the solution of the hydroxypropyl cellulose can be 0.1 mol / L.

[0052] In the present invention, the solution of the dibromoisobutyryl bromide is preferably obtained by dissolving the dibromoisobutyryl bromide in a solvent, and the solvent is preferably the same as the solvent used for preparing the solution of the hydroxypropyl cellulose.

[0053] In the present invention, the molar concentration of the solution of the dibromoisobutyryl bromide is preferably 0.01 to 0.1 mol / L, and in specific embodiments, it can be 0.01, 0.05 or 0.1 mol / L.

[0054] In the present invention, the mass ratio of the hydroxypropyl cellulose to the dibromoisobutyryl bromide is (5000 - 100000):(1 - 5), preferably 50000 - 100000:1, and in specific embodiments, it can be 50000:1, 60000:1, 70000:1, 80000:1, 90000:1 or 100000:1. The present invention controls the ratio of x to y by controlling the mass ratio of the hydroxypropyl cellulose to the dibromoisobutyryl bromide.

[0055] In the present invention, the mixing of the solution of the hydroxypropyl cellulose and the solution of the dibromoisobutyryl bromide preferably includes: dropping the solution of the dibromoisobutyryl bromide into the solution of the hydroxypropyl cellulose under the condition of 0 - 5°C. In the present invention, since the dibromoisobutyryl bromide has high reactivity, especially when undergoing an esterification reaction with the hydroxypropyl cellulose, the reaction will release heat. The present invention adds the dibromoisobutyryl bromide in the form of a solution and adds it in a low-temperature environment, which can effectively control the reaction rate and prevent side reactions caused by too violent a reaction.

[0056] In the present invention, the temperature of the esterification reaction is preferably 15 - 35°C, and the time is preferably 6 - 48 h; in specific embodiments, the temperature of the esterification reaction can be 15°C, 20°C, 25°C, 30°C or 35°C, and the time of the esterification reaction can be 6 h, 12 h, 24 h, 36 h or 48 h.

[0057] After completing the esterification reaction, the present invention performs rotary evaporation on the obtained esterification system. The obtained concentrate is dispersed in water and freeze-dried to obtain a hydroxypropyl cellulose bromide initiator.

[0058] In the present invention, the structure of the hydroxypropyl cellulose bromide initiator is shown in Formula 3:

[0059]

[0060] After obtaining the hydroxypropyl cellulose bromide initiator, the present invention dissolves the hydroxypropyl cellulose bromide initiator, SBMA, cuprous bromide, and N-containing organic ligand in a polar solvent and performs an atom transfer radical polymerization reaction under an inert gas protection to obtain the HPC-PSBMA.

[0061] In the present invention, the molar ratio of the hydroxypropyl cellulose bromide initiator to SBMA is (2-4):(40-60), preferably 2:(40-60), and in specific embodiments, it can be 2:40, 2:50, or 2:60.

[0062] In the present invention, the mass ratio of SBMA to cuprous bromide is preferably (40-60):(0.5-1), preferably (40-60):1, and in specific embodiments, it can be 40:1, 45:1, 50:1, 55:1, or 60:1. In the present invention, the role of cuprous bromide is to catalyze the atom transfer radical polymerization reaction as a catalyst.

[0063] In the present invention, the molar ratio of the N-containing organic ligand to cuprous bromide is preferably (0.5-2):(0.5-1), preferably (0.5-2):1, and in specific embodiments, it can be 0.5:1, 1:1, 1.5:1, or 2:1. In the present invention, the N-containing organic ligand is 2,2'-bipyridine or tris(2-dimethylaminoethyl)amine.

[0064] In the present invention, the polar solvent preferably includes one or more of dimethyl sulfoxide, water, and alcohol solvents, and the alcohol solvent preferably includes methanol and / or ethanol. The present invention has no special requirements for the amount of the polar solvent, as long as it can completely dissolve each raw material.

[0065] In the present invention, dissolving the hydroxypropyl cellulose bromide initiator, SBMA, cuprous bromide, and N-containing organic ligand in a polar solvent preferably includes: first dissolving the hydroxypropyl cellulose bromide initiator in the polar solvent, passing an inert gas through the resulting solution to remove oxygen, then adding the cuprous bromide and N-containing organic ligand to the solution under the protection of the inert gas, and finally adding the SBMA. The present invention does not particularly require the type of inert gas; any inert gas known in the art, such as nitrogen and argon, can be used. The purpose of deoxygenation in the present invention is to prevent oxygen from quenching free radicals, causing difficulty in polymerization initiation or a sudden drop in polymerization rate, thereby avoiding the initiation of side reactions that disrupt the catalytic equilibrium. Deoxygenation ensures reaction stability and good reproducibility.

[0066] In the present invention, the temperature of the atom transfer radical polymerization reaction is preferably 20°C to 35°C, and in specific embodiments, it can be 20°C, 25°C, 30°C, or 35°C. The reaction time of the atom transfer radical polymerization reaction is 10 to 48 hours, and in specific embodiments, it can be 10 hours, 24 hours, 36 hours, or 48 hours. The present invention controls the degree of polymerization of SBMA, i.e., the value of m in Formula 1, by controlling the reaction time of the atom transfer radical polymerization reaction. In the present invention, the atom transfer radical polymerization reaction is preferably carried out under stirring conditions.

[0067] In the present invention, the nitrogen-containing organic ligand first coordinates with the copper ions in the system, then interacts with the bromine on the initiator to promote halogen atom transfer. After the bromine atom is lost, the hydroxypropyl cellulose bromine initiator generates a primary free radical, which rapidly undergoes an addition reaction with the SBMA monomer in the system, triggering atom transfer radical polymerization (ATRP). This allows monomer molecules to connect individually to the growing chain, achieving polymer chain growth and yielding HPC-PSBMA.

[0068] After the reaction time is reached, the present invention preferably exposes the reaction system to air to quench the reaction, dialyzes the resulting product system, and freeze-dries the resulting solution to obtain pure HPC-PSBMA.

[0069] In the present invention, the dialysis is preferably water dialysis, and the molecular weight cutoff of the dialysis bag used is preferably 3000-10000; the dialysis time is preferably 48-120 hours, and in a specific embodiment it is 60 hours; the present invention preferably changes the water every 4-8 hours.

[0070] The present invention provides a lubricant solution comprising the HPC-PSBMA and an aqueous solvent.

[0071] In the present invention, the aqueous solvent preferably includes water, physiological saline or PBS buffer; the water is preferably deionized water; the physiological saline is preferably physiological saline with a sodium chloride content of 0.9% by mass; and the pH value of the PBS buffer is preferably 7.4.

[0072] In the present invention, the mass concentration of HPC-PSBMA in the lubricant solution is preferably 0.5 to 20 mg / mL, and in specific embodiments, it can be 0.5 mg / mL, 1 mg / mL, 2 mg / mL, 5 mg / mL, 10 mg / mL, 15 mg / mL or 20 mg / mL. In the present invention, since HPC-PSBMA is water-soluble, it can be dissolved in an aqueous solvent to obtain a lubricant solution.

[0073] In the present invention, HPC-PSBMA in the lubricant solution preferably exists as colloidal particles; the particle size of the colloidal particles is preferably 150 to 400 nm, and in specific embodiments, it can be 150 nm, 200 nm, 250 nm, 300 nm or 400 nm.

[0074] The present invention provides the application of the lubricant solution described in the above solution in reducing friction of medical devices. The present invention does not make special requirements on the specific types of the medical devices, and any medical devices that need to reduce friction well-known in the art can be used, such as medical catheters, contact lenses, implantable devices, and medical wearable devices.

[0075] In the present invention, the material of the medical device is preferably one or more of silicone rubber, polylactic acid, polyethylene and titanium alloy, and in a specific application example, it can be polydimethylsiloxane (PDMS).

[0076] The present invention does not make special limitations on the method of reducing friction. The medical device can be directly immersed in the lubricant solution and taken out, or the spin coating or coating method can be used, and these methods well-known in the art can be used. In application, the operation method of the present invention is simple and convenient.

[0077] The following is a detailed description of a hydroxypropyl cellulose grafted poly(3-[N,N-dimethyl-[2-(2-methylprop-2-enoyloxy)ethyl]ammonium] propane-1-sulfonate inner salt) provided by the present invention and its preparation and application in combination with examples, but they should not be construed as limiting the protection scope of the present invention.

[0078] Example 1

[0079] (1) Dissolve 2.0 g of HPC (weight average molecular weight of 100,000) in a round-bottomed flask containing 140 mL of dichloromethane. Subsequently, place the solution in an ice bath. Dissolve 28 μL of dibromoisobutyryl bromide in 20 mL of dichloromethane, and then slowly add it dropwise to the flask. Stir at 25 °C for 12 h for an esterification reaction to obtain a dichloromethane solution of HPC-Br. Concentrate the reaction mixture using a rotary evaporator and redisperse it in ultrapure water. Freeze-dry the obtained solution to obtain a hydroxypropyl cellulose bromide initiator, denoted as HPC-Br.

[0080] (2) Dissolve HPC-Br in 200 mL of dimethyl sulfoxide, and introduce nitrogen gas into the solution for 30 min to remove dissolved oxygen. Subsequently, add 45 mg of cuprous bromide and 100 mg of 2,2'-bipyridine under a nitrogen atmosphere, and then add 4 g of SBMA monomer. The reactant solution is stirred at 20 °C for 24 h for atom transfer radical polymerization reaction. After reaching the reaction time, it is quenched by exposure to air. The solution is subjected to water dialysis using a dialysis bag with a molecular weight cut-off of 3500 for 60 h, and the water is changed every 4 h. Subsequently, the solution is freeze-dried to obtain pure HPC-PSBMA. Among them, the ratio of x to y is 0.95:0.05, and m is 40.

[0081] The equation for atom transfer radical polymerization reaction is shown in Reaction Scheme 1:

[0082]

[0083] Structure Characterization

[0084] The chemical structures of the products obtained in each step of Example 1 were confirmed by nuclear magnetic resonance spectroscopy. Deuterium oxide (D2O) was used as the solvent in the nuclear magnetic resonance spectroscopy. As Figure 1 shown, peaks were observed at δ = 2.7 - 5.0 ppm and δ = 1.02 ppm for untreated HPC, corresponding to the hydrogen atoms in the sugar ring and the hydrogen atoms of the hydroxypropyl group, respectively. In the spectrum of HPC-Br, a new peak appeared at δ = 1.87 ppm, which was attributed to the methyl hydrogen atoms of 2-bromoisobutyryl bromide. In the spectrum of HPC-PSBMA, the peaks labeled e-j were the hydrogen atoms on the PSBMA side chain, and the results showed that they were in line with the target structure.

[0085] Water Solubility Characterization:

[0086] Weigh appropriate amounts of HPC, HPC-Br, and HPC-PSBMA from Example 1 respectively, and dissolve them in water to prepare aqueous solutions with a concentration of 10 mg / mL each. Observe the solution state and whether the Tyndall phenomenon occurs to verify their water solubility. The results are as Figure 2 shown.

[0087] As Figure 2 can be seen, HPC-PSBMA can be completely dispersed in the aqueous solution, improving the solubility of HPC-Br.

[0088] Morphology Characterization:

[0089] The critical micelle concentration of the HPC-PSBMA solution was tested, and the results are as Figure 3 shown. As Figure 3It can be seen that when the concentration of the HPC-PSBMA solution exceeds 0.023 mg / mL, HPC-PSBMA molecules will self-assemble to form micelles. Observed by atomic force microscopy, the morphology of the micelles is roughly circular, and the size is about 230 nm (see Figure 4 ).

[0090] Film-forming performance characterization:

[0091] To label and trace the synthesized HPC-PSBMA, an HPC-PSBMA-fluorescein isothiocyanate (FITC) sample was synthesized according to the following steps: First, 0.3 g of HPC-PSBMA prepared in Example 1 was dissolved in N,N-dimethylformamide (DMF, 25 mL) at 60 °C and continuously stirred until completely dissolved. In addition, FITC fluorescein was dissolved in 5 mL of DMF and then added dropwise to the HPC-PSBMA solution. To promote the reaction, 2 - 3 drops of dibutyltin dilaurate (DBTDL) solution were added. After reacting at 100 °C for 4 hours, the product was purified by water dialysis using a dialysis membrane with a molecular weight cut-off of 12,000 for 5 days, and the water was changed every 12 h. Finally, the purified product was freeze-dried to obtain an HPC-PSBMA-FITC conjugate. After the catheter was immersed in the HPC-PSBMA-FITC solution for 30 minutes, purple fluorescence appeared under ultraviolet light irradiation, indicating that the lubricant can adsorb on the surface of the catheter and form a uniform lubricating layer (see Figure 5 ).

[0092] Example 2

[0093] Compared with Example 1, the difference is that the volume of dibromoisobutyryl bromide added is 60 μL, and the rest of the operations are the same. In the obtained HPC-PSBMA, the ratio of x to y is 0.90:0.10.

[0094] Example 3

[0095] Compared with Example 1, the difference is that the volume of dibromoisobutyryl bromide added is 200 μL, and the rest of the operations are the same. In the obtained HPC-PSBMA, the ratio of x to y is 0.86:0.14.

[0096] Application Examples 1 - 6

[0097] The HPC-PSBMA of Example 1 was dissolved in PBS buffer with a pH value of 7.4 to prepare lubricant solutions with concentrations of 0.5 mg / mL, 1 mg / mL, 2 mg / mL, 5 mg / mL, 10 mg / mL, and 20 mg / mL respectively.

[0098] Comparative Example 1

[0099] Use PBS buffer solution with a pH value of 7.4 as the lubricant solution.

[0100] Comparative Example 2

[0101] Use HPC solution as the lubricant solution, with a concentration of 10 mg / mL, and the solvent is PBS buffer solution with a pH value of 7.4.

[0102] Comparative Example 3

[0103] Commercial paraffin lubricant.

[0104] Comparative Example 4

[0105] Commercial glycerol polyethylene glycol lubricant.

[0106] Lubrication performance test

[0107] Use a CSM reciprocating friction machine to characterize the lubrication performance of Application Examples 1 - 6. Conduct friction tests under the same environment (temperature 30 °C, relative humidity 20%). The load is 1 N, 0.1 mL of lubricant solution is dropped on the surface of the PDMS sheet, and the friction test is carried out. The friction pair is a PDMS thin sheet and a PDMS small ball, and the sliding speed is 1 Hz. The results are as Figure 6 shown. As Figure 6 can be seen, at a relatively low concentration, when the concentration of HPA - PSBMA is 0.5 mg / mL, it already shows good lubrication effect, and the average friction coefficient is 0.041. As the concentration increases, the average friction coefficient gradually decreases. When the concentration is 1 mg / mL, the average friction coefficient is 0.028; when the concentration is 2 mg / mL, the average friction coefficient is 0.027; when the concentration is 5 mg / mL, the average friction coefficient is 0.025; when the concentration is 10 mg / mL, the average friction coefficient is 0.024; when the concentration is 20 mg / mL, the average friction coefficient is 0.023. When the concentration reaches 10 mg / mL, the lubrication effect reaches stability.

[0108] Use a CSM reciprocating friction machine to characterize the lubrication performance of Application Example 5 (HPC - PSBMA concentration is 10 mg / mL) and Comparative Examples 1 - 4. Conduct friction tests under the same environment (temperature 30 °C, relative humidity 20%). The load is 1 N, 0.1 mL of lubricant solution is dropped on the surface of the catheter, and the friction test is carried out. The friction pair is a catheter (made of medical silicone) and a PDMS small ball, and the sliding speed is 1 Hz. The results are as Figure 7 and Figure 8 shown. As Figure 7As shown, the average friction coefficient of PBS buffer as a lubricant is 0.403, the average friction coefficient of HPC solution as a lubricant is 0.137, and the average friction coefficient of HPC-PSBMA is 0.020. Although the HPC solution exhibits a certain lubricating effect due to the interaction between its hydroxyl groups and water molecules, the zwitterionic groups of HPC-PSBMA usually have stronger hydration properties and can form a dense hydration layer in aqueous solution, thus providing a better lubricating effect. And Figure 8 shows that the average friction coefficient of paraffin lubricant is 0.056, and the average friction coefficient of glycerol polyethylene glycol lubricant is 0.044, indicating that the HPC-PSBMA of the present invention has better lubricating performance.

[0109] Biocompatibility test

[0110] L929 mouse fibroblasts were seeded in 96-well plates at a density of 5×10 3 / well and cultured overnight in an incubator at 37 °C with a CO2 volume concentration of 5%. Subsequently, the cells were co-cultured with lubricant solutions at different mass concentrations (0.01, 0.1, 1, 5, and 10 mg / mL, composed of HPC-PSBMA prepared in Example 1 and PBS buffer with a pH value of 7.4) for 7 days as the experimental group, and the control group did not add the lubricant solution. The culture medium was changed every two days during this period. After the culture was completed, the medium containing the samples was removed, and each well was washed three times with PBS buffer. Then, 100 μL of medium containing 0.5 mg / mL MTT was added to each well, and the cells were continued to be cultured at 5% CO2 and 37 °C for 4 h. The supernatant was discarded, 100 μL of dimethyl sulfoxide was added to each well, and the wells were gently shaken for 10 minutes to dissolve the crystals. Finally, the absorbance was measured at 570 nm to evaluate the cytotoxicity of the samples. And the relative viability was calculated (relative viability % = OD value of the experimental group / mean OD value of the control group × 100). As Figure 9 shown, Figure 9 in which control is the control group, and the cell viability measured by the MTT experiment was higher than 80% at all tested concentrations (including 0.01, 0.1, 1, 5, and 10 mg / mL). These results indicate that HPC-PSBMA has good biocompatibility and can be used in in vivo applications and in biomedical devices.

[0111] The above are only the preferred embodiments of the present invention. It should be noted that for those of ordinary skill in the art, without departing from the principle of the present invention, several improvements and refinements can be made, and these improvements and refinements should also be regarded as the protection scope of the present invention.

Claims

1. A hydroxypropyl cellulose grafted with poly(3-[N,N-dimethyl-[2-(2-methylprop-2-enoyloxy)ethyl]ammonium] propane-1-sulfonate inner salt), characterized in that, It has the structure shown in Formula 1: In Formula 1, R is -H or -CH2CH(OH)CH3; the ratio of x to y is (0.05 - 0.95):(0.95 - 0.05); m is an integer between 20 and 50.

2. The preparation method of the hydroxypropyl cellulose grafted poly(3-[N,N-dimethyl-[2-(2-methylprop-2-enoyloxy)ethyl]ammonium] propane-1-sulfonate) according to claim 1, comprising the following steps: Mix the solution of hydroxypropyl cellulose with the solution of dibromoisobutyryl bromide, and carry out an esterification reaction to obtain a hydroxypropyl cellulose bromine initiator; the structural formula of the hydroxypropyl cellulose is as shown in Formula 2, and the structural formula of the hydroxypropyl cellulose bromine initiator is as shown in Formula 3: The mass ratio of the hydroxypropyl cellulose to the dibromoisobutyryl bromide is (5000 - 100000):(1 - 5); In Formulas 2 - 3, R is -H or -CH2CH(OH)CH3; Dissolve the hydroxypropyl cellulose bromine initiator, (3-[N,N-dimethyl-[2-(2-methylprop-2-enoyloxy)ethyl]ammonium] propane-1-sulfonate), copper bromide and the N-containing organic ligand into a polar solvent, and carry out an atom transfer radical polymerization reaction under the protection of an inert gas to obtain the hydroxypropyl cellulose grafted poly(3-[N,N-dimethyl-[2-(2-methylprop-2-enoyloxy)ethyl]ammonium] propane-1-sulfonate); The N-containing organic ligand is tris(2-dimethylaminoethyl)amine or 2,2'-bipyridine; The molar ratio of the hydroxypropyl cellulose bromine initiator to (3-[N,N-dimethyl-[2-(2-methylprop-2-enoyloxy)ethyl]ammonium] propane-1-sulfonate) is (2 - 4):(40 - 60); The time of the atom transfer radical polymerization reaction is 10 - 48 h.

3. The preparation method according to claim 2, characterized in that, The weight average molecular weight of the hydroxypropyl cellulose is 50,000 - 200,000.

4. The preparation method according to claim 2 or 3, characterized in that, The temperature of the esterification reaction is 15 - 35 °C, and the time is 6 - 48 h.

5. The preparation method according to claim 2, characterized in that, The molar ratio of the N-containing organic ligand to copper bromide is (0.8 - 2):(0.5 - 1); The mass ratio of the 3-[N,N-dimethyl-[2-(2-methylprop-2-enoyloxy)ethyl]ammonium] propane-1-sulfonate to copper bromide is (40 - 60):(0.5 - 1).

6. The preparation method according to claim 2 or 5, characterized in that The temperature of the atom transfer radical polymerization reaction is 20 - 35 °C.

7. A lubricant solution, characterized in that, It includes the hydroxypropyl cellulose grafted poly(3-[N,N-dimethyl-[2-(2-methylprop-2-enoyloxy)ethyl]ammonium] propane-1-sulfonate) according to claim 1 and an aqueous solvent.

8. The lubricant solution according to claim 7, wherein, The mass concentration of the hydroxypropyl cellulose grafted poly(3-[N,N-dimethyl-[2-(2-methylprop-2-enoyloxy)ethyl]ammonium] propane-1-sulfonate) in the lubricant solution is 0.5 - 20 mg / mL.

9. The lubricant solution according to claim 7 or 8, characterized in that, The aqueous solvent includes water, physiological saline or PBS buffer solution.

10. The application of the lubricant solution according to any one of claims 7 - 9 in reducing friction of medical devices.

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