CN115819671A - Copolymer containing NVP structure and application thereof in lubricating coating for interventional catheter - Google Patents

Abstract

The invention discloses a copolymer containing NVP structure, which is characterized in that it is formed by copolymerization of two monomers, one of the monomers is NVP, and the other monomer is catechol and double bond structure in the structure. substituted alkenes. Also disclosed is its application as a lubricating coating for interventional catheters, as well as the corresponding lubricating coating mixture for interventional catheters and interventional catheters. The copolymer containing NVP structure provided by the present invention, when in contact with water or water in blood, interstitial fluid, etc., will quickly absorb water to produce lubricating properties, reducing the friction on the surface of the catheter to 1/10 or even lower than the original, thereby producing Lubricating effect, and in continuous friction, it can withstand repeated friction and maintain low friction. Compared with polyvinylpyrrolidone that does not contain catechol structure but contains NVP structure, the number of frictions that can be tolerated is increased by 5 Times or even more, showing a better degree of firmness.

Description

Copolymer Containing NVP Structure and Its Application in Lubricant Coating for Intervention Catheter

technical field

The invention relates to a copolymer containing NVP structure and its application as a lubricating coating for interventional catheters, belonging to the technical field of medical devices.

Background technique

Interventional therapy is based on the original lumens of the human body such as blood vessels, trachea, esophagus, urethra, etc., through guide wires, catheters, etc. to establish access channels, and then treat local lesions. The specific methods used include ablation, dilation, Embolization or even resection. In interventional therapy devices, the guide wire is often a metal wire made of stainless steel, nickel-titanium alloy and other materials, while the catheter is often made of various nylon, polyolefin, polyurethane and other materials. When the guide wire or catheter enters the cavity, it will rub against the cavity wall, which may cause a series of reactions such as damage to the cavity wall and even spasm, which is often not conducive to treatment. Therefore, such interventional devices often need to have a low coefficient of friction to reduce friction. In addition to optimizing the catheter material itself and using materials with a lower friction coefficient as much as possible, the use of coating technology to provide lubricity and reduce the friction coefficient between the catheter and the lumen wall is the most important means.

Now commonly used coating materials include polyvinylpyrrolidone (PVP), polymers polymerized from vinylpyrrolidone (NVP), polyacrylic acid and its copolymers, polyacrylamide, sodium alginate, hyaluronic acid, polyethylene glycol Alcohol, etc., of which PVP is mostly used in practice, which can significantly reduce the friction coefficient between the catheter and the lumen wall. However, it is not resistant to repeated use, and the coefficient of friction will decrease rapidly under the condition of repeated use. Therefore, finding a kind of coating material that not only has a good lubricating effect, but also can be used repeatedly for a long time has become the current key.

Contents of the invention

The object of the present invention is to provide a type of copolymer based on vinylpyrrolidone (NVP) monomer, which has hydrophilicity and can be dissolved in water and alcohol solvents. Dissolve this type of copolymer and other additives in an alcoholic solvent to obtain a coating solution, which is then coated on the surface of the catheter and cured and dried to form a coating surface. When in contact with water, it quickly absorbs water to produce good lubricity and wear resistance Sex, play a lubricating role.

The object of the present invention is achieved through the following technical solutions:

A copolymer containing NVP structure is characterized in that it is formed by copolymerization of two monomers, one of which is NVP, and the other monomer is a substituted olefin containing both catechol and double bond structure in the structure.

Preferably, its structure is shown in general formula (I):

Wherein R is an alkyl group, an ester group or an amido group;

m/(m+n)>0.5;

The molecular weight of the copolymer is between 10 million and 2 million.

Preferably, the molecular weight of the copolymer is 50,000-1.5 million.

Preferably, the molecular weight of the copolymer is 600,000-1.5 million.

Preferably, m/(m+n)>0.8.

Preferably, the R is a methylene group, an acetyl ester group or an acetamide group.

The invention also discloses the application of the above-mentioned copolymer containing the NVP structure in the lubricating coating for interventional catheters.

The invention also discloses a lubricating coating for an intervention catheter, which is characterized in that it includes the above-mentioned copolymer containing the NVP structure and a solvent.

Preferably, the mass-volume concentration of the copolymer containing NVP structure is 1-20%.

Preferably, the solvent is water, or a mixture of water and alcoholic solvents.

Preferably, a leveling agent and a stabilizer are also included, and the sum of the mass concentrations of the leveling agent and the stabilizer does not exceed 1%.

The invention also discloses the preparation method of the above-mentioned copolymer containing NVP structure, which is characterized in that the step is to dissolve the NVP monomer in a solvent, then add a substituted olefin containing catechol and a double bond structure in the structure, and stir After uniformity, the initiator is added to carry out the copolymerization reaction, and the copolymer is obtained after purification.

Available solvents include but are not limited to water, alcohol solvents such as methanol, ethanol, isopropanol, etc., ketone solvents such as acetone, methyl ethyl ketone, etc. and other specific conditions to choose; the available reaction temperature is between 40-100°C, the reaction time generally takes several hours to tens of hours, the more optimal time is 2-24 hours, and the more optimal time is 6-12 hours.

For purification, conventional purification methods, such as dialysis or precipitation washing, can be used to remove residual small molecules.

The invention also discloses an interventional catheter, the surface of which is provided with a coating, which is obtained by coating the solution of a copolymer containing NVP on the surface of the catheter and drying to remove the solvent. The thickness of the coating is about 1-50 μm. The preferred thickness is 5-20 μm. Heating is required during drying. The heating temperature is higher than room temperature but not more than 60°C. The preferred temperature is 50±5°C. At this temperature, the solvent is gradually volatilized and removed to form a coating on the surface of the catheter. And need to avoid contact with water during storage.

The copolymer containing the NVP structure provided by the present invention, and the coating solution formed based on the series of copolymers, form a coating on the surface of the catheter. When the coating contacts water, blood, tissue fluid, etc., it will quickly absorb water and produce Lubricating properties, the friction on the surface of the catheter is reduced to 1/10 or even lower than the original, thereby producing a lubricating effect, and in continuous friction, it can withstand repeated friction and maintain low friction, and does not contain catechin Compared with polyvinylpyrrolidone with phenolic structure but containing NVP structure, the friction coefficient that can be tolerated is increased by 5 times or more, showing a better degree of firmness. The introduction of monomers containing catechol structure enables this low-friction state to last longer and show a better degree of firmness. It has a significant intentional effect on reducing friction during interventional therapy, reducing damage to human cavity due to friction, and improving the experience of patients and medical staff during treatment.

The present invention obtains copolymers through the copolymerization of NVP and different monomers. In addition to utilizing the hydrophilic characteristics of PVP to bring lubricating properties, the introduction of comonomers can enhance the adhesion to the substrate to obtain better hydrophilicity. The abrasion resistance and firmness of the coating can be used to obtain a lubricating coating for intervention catheters, and the invention also provides a preparation and application method for coatings based on these copolymers.

Description of drawings

Fig. 1 is the general structural formula of the copolymer containing NVP structure.

Fig. 2 is a schematic diagram of the structure of a monomer containing both catechol and a double bond structure.

Fig. 3 is the structural formula of typical monomer containing catechol and double bond structure at the same time, and wherein box part is the embodiment of R in Fig. 2, (a) is 4-allyl catechol, (b) is 3,4-dihydroxyphenethyl acrylate, (c) is dopamine methacrylamide.

Figure 4 shows the friction test results of the dry coating.

Fig. 5 is the friction force result measured after the coating in Example 1 absorbs water.

Fig. 6 is the friction force result measured after the coating in Example 2 absorbs water.

Fig. 7 is the friction force result measured after the coating in Comparative Example 1 absorbs water.

Specific implementation method:

The present invention will be further described below in conjunction with the examples, but the description of the examples does not create any limitation on the protection scope of the present invention.

Fig. 1 is the structural general formula of the copolymer containing NVP structure of the present invention, and Fig. 2 is wherein a monomer contains catechol and the structural representation of the substituted olefin of double bond structure simultaneously, and several typical monomers are as shown in Fig. 3 As shown, the boxes on the structural formulas of each monomer are Rs of different structures.

Example 1: 11.1g (0.1mol) of commercially available NVP monomer, with a purity >99%, was dissolved in 20mL of pure water, 1.5g (0.01mol) of 4-allyl catechol was added, stirred to dissolve evenly, and added 0.1 mL of 30% hydrogen peroxide was gradually heated to 50±5°C for 4 hours, and the system gradually became viscous. The above system was put into a dialysis bag with a molecular weight cut-off of 3500 and dialyzed with pure water for 24 hours. During this period, the water was changed several times to remove residual small molecules. After completion, it was lyophilized to obtain a white solid. The total molecular weight of the finished product is about 800,000, of which NVP accounts for about 90%.

Dissolve the above white solid polymer in 95% ethanol solution at a concentration of 5%, add 0.2% TegoFlow 370 leveling agent, 0.05% concentration of antioxidant 1010, stir and dissolve evenly. Immerse the nylon catheter in the solution for 1 minute, take it out and dry it until there is no visible surface solvent, hang it in an oven at 50±5°C for 1 hour, and obtain a catheter coated with a hydrophilic solution coating. There was no apparent macroscopic coating on this catheter, and friction was checked dry, similar to uncoated catheters, with no significant difference. The friction force measured by the friction tester with a load of 1Kg is about 150gf, as shown in Figure 4.

The catheter coated with the coating was immersed in water for 30 seconds, taken out to measure the friction force, and it was found that the friction force had been reduced to 0.3gf, showing obvious lubricating properties. Using the friction tester to repeatedly test the reciprocating friction, it was observed that the friction force on the surface of the catheter gradually increased in the later stage, but before that, the catheter showed significant low friction and high lubrication characteristics, and could support reciprocating cycles up to 40 times. Can maintain friction below 5gf (Figure 5).

Example 2: Similar to Example 1, but the second monomer used is 3,4-dihydroxyphenylethyl acrylate, the amount is 1g (5mmol), after polymerization, a white solid powder similar to Example 1 is obtained , with a molecular weight of about 1 million, of which NVP accounts for about 95%. Dissolve it in 85% isopropanol at a concentration of 3% to form a solution, apply it on the catheter, and measure the friction force after absorbing water. After 40 cycles of friction, it can still be lower than 1gf, (as shown in Figure 6) .

Example 3: Similar to Example 1, but the second monomer used is dopamine methacrylamide in an amount of 1 g (5 mmol). After polymerization, a white solid powder similar to Example 1 is obtained, with a molecular weight of about 800,000. NVP accounts for about 95%. It is soluble in ethanol-water mixed solvent, prepared into a 4% concentration solution and coated on the catheter, and the coating is obtained after drying. After absorbing water, the friction force of 1Kg load is lower than 2gf.

Comparative example 1: As a comparative example, use commercially available PVP with a molecular weight of 1.3 million, dissolve it in 90% isopropanol solution at a concentration of 5%, add 0.2% Tego Flow 370 leveling agent, 0.05% concentration of anti Oxygen agent 1010, stirred and dissolved evenly, coated on the catheter, measured friction after absorption, the initial friction was lower than 2gf, but after 6 cycles, the friction has risen to about 100gf, after about 20 cycles, the friction has been Recovered to about 150gf.

The above-mentioned embodiments are only to illustrate the technical concept and characteristics of the present invention. Equivalent changes or modifications made in the spirit shall fall within the protection scope of the present invention.

Claims (15)

1. A copolymer containing NVP structure is characterized in that it is formed by copolymerization of two monomers, one of the monomers is NVP, and the other monomer is a substituted olefin containing catechol and double bond structure in the structure . 2. The copolymer containing NVP structure according to claim 1, characterized in that its structure is as shown in general formula (I):

(I) Wherein R is an alkyl group, an ester group or an amido group; m/(m+n)>0.5; The molecular weight of the copolymer is between 10 million and 2 million. 3. The copolymer containing NVP structure according to claim 2, characterized in that the molecular weight of the copolymer is between 50,000 and 1,500,000. 4. The copolymer containing NVP structure according to claim 2, characterized in that the molecular weight of the copolymer is between 600,000 and 1,500,000. 5. The copolymer containing NVP structure according to claim 2, characterized in that m/(m+n)>0.8. 6. The copolymer containing NVP structure according to claim 1, characterized in that said R is a methylene group, an acetyl ester group or an acetamide group. 7. The application of the copolymer containing the NVP structure described in any one of claims 1-6 in lubricating coatings for interventional catheters. 8. A lubricating coating mixture for an interventional catheter, characterized in that it comprises the copolymer containing the NVP structure described in any one of claims 1-6, and a solvent. 9. The lubricating coating mixture for interventional catheter according to claim 8, characterized in that the mass-volume concentration of the copolymer containing NVP structure is 1-20%. 10. The lubricating coating mixture for interventional catheters according to claim 8, characterized in that the solvent is water, or a mixture of water and alcohol solvents. 11. The lubricating coating mixture for interventional catheter according to claim 8, characterized in that it also includes a leveling agent and a stabilizing agent, and the sum of the mass concentrations of the leveling agent and the stabilizing agent is no more than 1%. 12. An interventional catheter, characterized in that a coating is provided on its surface, and the coating is the lubricating coating mixture for an interventional catheter according to any one of claims 8-11. 13. The interventional catheter according to claim 12, characterized in that the surface coating is formed by applying the lubricating coating mixture for the interventional catheter and then drying to remove the solvent. 14. The interventional catheter according to claim 13, characterized in that the thickness of the coating is 1-50 μm. 15. The interventional catheter according to claim 13, characterized in that the thickness of the coating is 5-20 μm.

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