CN107412883B - A kind of hydrophilic super slippery coating for the surface of medical equipment and preparation method thereof - Google Patents

Abstract

The invention provides a hydrophilic super-slippery coating used on the surface of a medical device and a preparation method thereof. The hydrophilic super-slippery coating includes a bottom layer and a surface layer, and uses the principle of similarity and compatibility to firmly combine the bottom layer with the substrate. Utilize the chemical bond and intermolecular force formed by ultraviolet grafting to firmly connect the surface layer and the bottom layer. Using dipping-lifting technology, the surface of the medical device is first immersed in the bottom layer solution, and partially cured by ultraviolet radiation; then the partially cured bottom layer of the medical device is dipped in the top coat, and after complete curing under ultraviolet light, the top layer Evenly and stably distributed on the bottom layer. The hydrophilic super-slip coating of the present invention can be quickly cured under ultraviolet light, and the obtained hydrophilic coating has excellent lubricity and durability, and can effectively reduce friction and damage to tissues during insertion. The raw material of water super slippery coating is easy to get and the price is low.

Description

A kind of hydrophilic super slippery coating for the surface of medical equipment and preparation method thereof

technical field

The invention belongs to the field of medical devices, and relates to a hydrophilic super-slip coating and a preparation method thereof.

Background technique

Interventional medicine is a low-invasive or minimally invasive technology. It has become one of the three major clinical medicines alongside surgery and internal medicine. Imaging equipment and interventional devices are the pillars of interventional medicine.

Lubricity is one of the most important properties of interventional devices (catheters, guide wires). When inserting or pulling out of the human body, the surface of these instruments is required to be lubricated, so as to reduce damage and adhesion to the tissue and relieve the pain of the patient. At present, there are two ways to solve the problem of lubricity, one is to use lubricating oil, but the lubricity obtained by this treatment method is poor, it is difficult to last and it is not conducive to operation. One is to form a lubricious hydrophilic coating on the surface of the device.

Since the interventional device moves in the body and stays for a period of time, the hydrophilic coating on the interventional device must take into account both hydrophilic lubrication and stability, that is, the coating must not fall off after repeated friction and maintain good comprehensive performance. Usually, hydrophilic compounds can be immobilized by means of chemical bond connection or physical entanglement, and such technologies are gradually being widely used.

At present, there are very few hydrophilic super-slip coating products used on the surface of medical devices in China, and most of these products are monopolized by foreign countries.

Contents of the invention

Aiming at the problems existing in the prior art, the invention provides a hydrophilic super-slip coating for the surface of a medical device and a preparation method thereof.

The technical scheme of the invention is: a hydrophilic super-slip coating includes a bottom layer and a surface layer, and the two layers are connected by chemical bonds and intermolecular forces. The bottom layer is a cross-linked network structure, which is a connecting layer that provides bonding cross-linking points for the surface layer, and is obtained by dipping the surface of the medical device into the primer coating and curing by ultraviolet light. The surface layer is a hydrophilic layer, which is a hydrogel coating with an interpenetrating network structure, and is obtained by dipping the surface of the medical device coated with the bottom layer into the surface layer coating and curing by ultraviolet light. The base layer and the base material are firmly bonded using the principle of similarity and compatibility.

The primer is composed of urethane acrylate, active diluent, first photoinitiator and first organic solvent. The mass ratio of polyurethane acrylate to reactive diluent is 1:0.1-10, the first photoinitiator is 2%-8% of the total mass of the primer after curing, and the mass of the first organic solvent is 70% of the total mass of the primer -99%.

The surface coating is composed of monomers and/or polymers with two or more photopolymerizable functional groups, biocompatible hydrophilic polymers, a second photoinitiator and a second organic solvent. The mass ratio of monomers and/or polymers with functional groups to biocompatible hydrophilic polymers is 1:0.1-10, and the second photoinitiator is 0.5%-5% of the total mass of the surface coating after curing, The mass of the second organic solvent is 60%-99% of the total mass of the surface coating.

The preparation method of above-mentioned hydrophilic super slippery coating, comprises the following steps:

The first step is to prepare the primer

1.1) Preparation of polyurethane acrylate prepolymer

Method 1: Under mechanical stirring, add diisocyanate and acrylate hydroxyester into the reactor, react at 15-60°C for 2-24h to obtain the intermediate; then raise the temperature to 60-90°C, add polyether/ester binary Alcohol and catalyst stannous octoate react for 1-24 hours under the action of stannous octoate to obtain polyurethane acrylate prepolymer.

Method 2: Under mechanical stirring, add diisocyanate and polyether/ester diol into the reactor, react at 60-90°C for 1-24h to obtain an intermediate; then cool down to 15-60°C, add acrylic acid hydroxyl Catalyst and stannous octoate react for 2-24 hours under the action of stannous octoate to obtain polyurethane acrylate prepolymer.

The diisocyanate described in the two methods includes: one of 2,4-toluene diisocyanate, isophorone diisocyanate, hexamethylene-1,6-diisocyanate, and diphenylmethane diisocyanate. The hydroxy acrylate includes: one or more of hydroxyethyl (meth)acrylate, hydroxypropyl (meth)acrylate, and hydroxybutyl (meth)acrylate. The polyether/ester diols include: one or more of polyethylene glycol, polypropylene glycol, polytetrahydrofuran diol, polycarbonate diol, polycaprolactone diol, number average molecular weight In the range of 200-200000.

1.2) Dissolve the urethane acrylate prepolymer, reactive diluent and first photoinitiator in the first organic solvent, and stir for 1-2 hours in the dark at room temperature to form a transparent and uniform film with a viscosity of 1-10 mm ² /s The bottom layer solution, namely obtains the bottom layer paint. The mass ratio of described urethane acrylate and reactive diluent is

1: (0.1-10); the first photoinitiator is 2%-8% of the total mass of the primer after curing, and the quality of the first organic solvent is 70%-99% of the total mass of the primer.

Described reactive diluent is selected from one or both of tripropylene glycol diacrylate, polyethylene glycol diacrylate, 1,6-hexanediol diacrylate, pentaerythritol tripropionate, pentaerythritol tetraacrylate more than one species. The first organic solvent is selected from one or more of water, ethanol, isopropanol, acetone, butanone, and ethyl acetate. The first photoinitiator is selected from 2-hydroxyl-4'(2-hydroxyethoxy)-2-methylpropiophenone (Irgacure 2959), 1-hydroxycyclohexyl phenylacetone (Irgacure 184), 2 -Hydroxy-2methyl-1-phenylacetone (Irgacure 1173), 2-methyl-1-[4-(methylthiophenyl)-2morpholino-1-propanone] (Irgacure 907), 2 -Phenylbenzyl-2-dimethylamine-1-(4-morpholinebenzylphenyl)butanone (Irgacure 369), phenylbis(2,4,6-trimethylbenzoyl)phosphine oxide ( One or more of Irgacure 819), benzophenone, etc.

The second step is to prepare the top coat

Dissolve monomers and/or polymers with two or more photopolymerizable functional groups, biocompatible hydrophilic polymers, and a second photoinitiator in a second organic solvent, and stir in the dark at room temperature After 1-2 hours, a transparent and uniform surface layer solution with a viscosity of 17-55 mm ² /s is formed to obtain the surface layer coating. The mass ratio of the monomer and/or polymer with the functional group to the biocompatible hydrophilic polymer is 1:(0.1-10), and the second photoinitiator is 0.5% of the total mass of the surface coating after curing. %-5%, the mass of the second organic solvent is 60%-99% of the total mass of the surface coating.

The monomers and/or polymers with two or more photopolymerizable functional groups are selected from unsaturated esters and unsaturated ethers such as tripropylene glycol diacrylate, polyethylene glycol diacrylate ester, 1,6-hexanediol diacrylate, pentaerythritol tripropionate, pentaerythritol tetraacrylate. The biocompatible hydrophilic polymer is selected from polyvinylpyrrolidone, polyvinyl alcohol, polyurethane, polyethylene glycol, sodium polyacrylate, polyacrylamide, polyacrylic acid-acrylamide partial sodium salt, starch, fiber One or two or more of glycosides, alginic acid, hyaluronic acid, chitosan, and collagen; the number-average molecular weight of the hydrophilic polymer is in the range of 2,000-5,000,000. The second organic solvent is selected from one or more of water, ethanol, isopropanol, acetone, butanone, and ethyl acetate. The second photoinitiator is selected from 2-hydroxyl-4'(2-hydroxyethoxy)-2-methylpropiophenone (Irgacure 2959), 1-hydroxycyclohexyl phenylacetone (Irgacure 184), 2 -Hydroxy-2methyl-1-phenylacetone (Irgacure 1173), 2-methyl-1-[4-(methylthiophenyl)-2morpholino-1-propanone] (Irgacure907), 2- Phenylbenzyl-2-dimethylamine-1-(4-morpholinebenzylphenyl)butanone (Irgacure 369), phenylbis(2,4,6-trimethylbenzoyl)phosphine oxide (Irgacure 819), one or more of benzophenone, etc.

The third step is to prepare a hydrophilic super slippery coating

Apply the primer on the surface of the medical device, irradiate with ultraviolet light for 1-60s, and form a primer on the surface of the medical device after the primer is cured, then apply the top coat on the bottom, irradiate with ultraviolet light for 60-360s, and the top coat Cured to form a hydrophilic super-slip coating on the surface of medical devices. The ultraviolet energy density is 10mw/cm ² -120mw/cm ² .

The coating method is a dipping-pulling method, the dipping time is 1-30s, and the pulling speed is 5-150mm/min. Both the bottom layer and the surface layer are solidified by rotating, and the rotating speed is 3-60rpm/min.

The beneficial effects of the present invention are:

The hydrophilic super-slip coating and its preparation method of the present invention, by constructing a double-layer (bottom layer and surface layer) coating system, the bottom layer is used as an intermediate connection layer, on the one hand, relying on the force generated by similar compatibility to firmly adhere to the base material On the one hand, it provides bonding and cross-linking points for the surface layer. And because the same component is contained in the primer and the top coat, the intermolecular forces produced by the similar compatibility of the two layers are combined more firmly. The hydrophilic coating has both excellent hydrophilic lubricating properties and excellent adhesion.

The invention utilizes the ultraviolet curing technology, can shorten the curing time to several minutes, greatly increases the production efficiency, and is beneficial to reduce the production cost.

The present invention is a layer of transparent film in dry state, which is convenient for packaging and storage.

Detailed ways

In order to make the technical solutions and advantages of the present invention clearer, the following examples are used to further describe in detail, but this does not represent a limitation to this patent.

Prepare the example

Preparation of urethane acrylate prepolymer 1

Add 10.45g of 2,4-toluene diisocyanate and 30g of polytetrahydrofuran 1000 (number-average molecular weight: 1000) into the reactor, mechanically stir at 60°C for 4 hours to obtain an intermediate, lower the temperature to 40°C, and add 7.69g of ( Hydroxybutyl methacrylate and 0.077 g of stannous octoate were reacted for 3 hours to obtain urethane acrylate prepolymer 1.

Preparation of urethane acrylate prepolymer 2

Add 10.45g of 2,4-toluene diisocyanate and 7.69g of hydroxybutyl (meth)acrylate into the reactor, mechanically stir at 40°C for 3 hours to obtain an intermediate prepolymer, raise the temperature to 60°C, and add 60g of polytetrahydrofuran 2000 (the number average molecular weight is 2000) and 0.077g of stannous octoate were reacted for 6 hours to obtain the polyurethane acrylate prepolymer 2.

Preparation of urethane acrylate prepolymer 3

Add 13.34g of isophorone diisocyanate and 60g of polyethylene glycol 2000 into the reactor, mechanically stir at 60°C for 6h to obtain an intermediate prepolymer, cool down to 40°C, and add 7.809g of hydroxyethyl methacrylate and 0.078g of stannous octoate were reacted for 3h to obtain urethane acrylate prepolymer 3.

Preparation of urethane acrylate prepolymer 4

Add 13.34 g of isophorone diisocyanate and 30 g of polyethylene glycol 1000 into the reactor, mechanically stir at 60°C for 4 hours to obtain an intermediate prepolymer, cool down to 40°C, and add 7.809g of hydroxyethyl methacrylate and 0.078g of stannous octoate were reacted for 3h to obtain urethane acrylate prepolymer 4.

The following examples 1-3 all adopt the urethane acrylate prepared in the preparation example as the reaction raw material.

Example 1

(1) Polyurethane acrylate prepolymer 1, polyethylene glycol dipropionate 1000 (obtained by polyethylene glycol capping with a number average molecular weight of 1000), Irgacure 2959 are dissolved in a mixed solvent of ethanol and deionized water , stirring at room temperature for 1-2h in the dark to obtain a primer; wherein the mass ratio of polyurethane acrylate to polyethylene glycol dipropionate 1000 is 2:1, Irgacure 2959 accounts for 5% of the total mass of the primer after curing, ethanol Water accounts for 94% of the mass of the primer.

Dissolve polyethylene glycol diacrylate 1000, polyethylene glycol 20000 (number-average molecular weight: 20000), and Irgacure2959 in deionized water, and stir at room temperature for 1-2 hours in the dark to obtain a surface coating; wherein polyethylene glycol diacrylate The mass ratio of ester 1000 to polyethylene glycol 20000 is 1:4, the photoinitiator is 3% of the total mass of the surface coating after curing, and the deionized water accounts for 80% of the surface coating.

(2) Apply the primer to the surface of the medical device, irradiate with ultraviolet light for 10s, and then apply the topcoat on the cured primer, and cure with ultraviolet light for 300s. The desired coating can be obtained on the surface of the medical device.

Lubricity test: Place the medical device coated with a hydrophilic coating on a self-made modified universal testing machine, one end is fixed in a fixture that applies a holding force, and the other end is connected to a sensor. The test is performed at room temperature. The holding force is 5N, and the test medium for water. Compared with the uncoated sample, the difference in friction value reflects the hydrophilic lubrication performance of the hydrophilic coating.

Persistence test: repeatedly test the lubrication performance, and the reproducibility of friction reflects the durability and wear resistance of the hydrophilic coating.

The test results show that: after the hydrophilic coating is prepared on the surface of the medical device in this implementation example, the friction amplitude is reduced by more than 95%, indicating that the coating has excellent lubricity. After multiple frictions, the friction amplitude reduction is still greater than 95%. %, indicating that the coating has excellent durability and wear resistance.

Example 2

(1) Polyurethane acrylate prepolymer 2, pentaerythritol tetraacrylate, and benzophenone are dissolved in ethanol, and stirred at room temperature in the dark for 1-2h to obtain a primer; wherein the mass ratio of polyurethane acrylate to pentaerythritol tetraacrylate The ratio is 1:1, the photoinitiator is 5% of the total mass of the primer after curing, and ethanol accounts for 85% of the mass of the primer.

Dissolve pentaerythritol tetraacrylate, polyvinylpyrrolidone K30 (number average molecular weight 45000-58000), benzophenone, and Irgacure 1173 in ionized water, and stir at room temperature for 1-2 hours in the dark to obtain a top coat; wherein pentaerythritol tetraacrylate The mass ratio to polyvinylpyrrolidone is 3:1, and deionized water accounts for 85% of the surface coating.

(2) Apply the primer to the surface of the medical device, irradiate with ultraviolet light for 20s, then apply the topcoat on the cured primer, and cure with UV for 320s. The desired coating can be obtained on the surface of the medical device.

In this example, the test method of lubricity and durability is the same as that of Example 1, and the test results show that after the hydrophilic coating is prepared on the surface of the medical device in this example, the magnitude of friction decreases by more than 95%, indicating that the coating has excellent After multiple frictions, the friction reduction is still greater than 95%, indicating that the coating has excellent durability and wear resistance.

Example 3

(1) Dissolve urethane acrylate prepolymer 3, polyethylene glycol diacrylate 600, and benzophenone in ethanol, and stir at room temperature in the dark for 1-2 hours to obtain a primer; wherein urethane acrylate and polyethylene glycol The mass ratio of alcohol diacrylate 600 is 1:1, benzophenone is 4% of the cured primer, and ethanol accounts for 75% of the primer mass.

Dissolve polyethylene glycol diacrylate 600, polyacrylic acid-acrylamide partial sodium salt, and benzophenone in a mixed solvent of ionized water and ethanol, and stir at room temperature for 1-2 hours in the dark to obtain a top coat; The mass ratio of alcohol diacrylate 600 to polyacrylic acid-acrylamide partial sodium salt is 1:4, the photoinitiator is 4% of the total mass of the surface coating after curing, and deionized water and ethanol account for 93% of the surface coating. The mass ratio of ionized water to ethanol is 1:1.

The partial sodium salt of polyacrylic acid-acrylamide is a product of Sigma-Aldrich with a number average molecular weight of 150,000.

(2) Apply the primer to the surface of the medical device, irradiate with ultraviolet light for 15s, then apply the topcoat on the cured primer, and cure with UV for 360s. The desired coating can be obtained on the surface of the medical device.

In this example, the test method of lubricity and durability is the same as that of Example 1, and the test results show that after the hydrophilic coating is prepared on the surface of the medical device in this example, the magnitude of friction decreases by more than 95%, indicating that the coating has excellent After multiple frictions, the friction reduction is still greater than 95%, indicating that the coating has excellent durability and wear resistance.

Claims (8)

1. A hydrophilic super-slip coating for the surface of a medical instrument is characterized by comprising a bottom layer and a surface layer, wherein the two layers are connected through a chemical bond formed by ultraviolet grafting and intermolecular force; the bottom layer is of a cross-linked network structure, is used for providing a connecting layer of bonding cross-linking points for the surface layer, is obtained by dipping the surface of the medical instrument in the bottom layer coating and performing ultraviolet curing; the surface layer is a hydrophilic layer, is a hydrogel coating with an interpenetrating network structure, is obtained by dipping the surface of the medical instrument coated with the bottom layer in the surface layer coating and performing ultraviolet curing;

The primer consists of polyurethane acrylate, a reactive diluent, a first photoinitiator and a first organic solvent;

The surface layer coating consists of monomers and/or polymers with two or more than two photopolymerization functional groups, a biocompatible hydrophilic polymer, a second photoinitiator and a second organic solvent;

The viscosity of the bottom coating is 1-10mm²The mass ratio of the polyurethane acrylate to the reactive diluent is 1:0.1-10, the mass of the first photoinitiator is 2% -8% of the total mass of the primer after curing, and the mass of the first organic solvent is 70% -99% of the total mass of the primer;

The viscosity of the surface coating is 17-55mm²And/or the mass ratio of the monomer with the functional group and/or the polymer to the biocompatible hydrophilic polymer is 1:0.1-10, the mass of the second photoinitiator is 0.5-5% of the total mass of the surface layer coating after curing, and the mass of the second organic solvent is 60-99% of the total mass of the surface layer coating.

2. A method for preparing a hydrophilic ultra-slip coating according to claim 1, characterized by the steps of:

First, preparing a primer

1.1) preparation of a urethane acrylate prepolymer

The method comprises the following steps: after uniformly mixing diisocyanate and hydroxyl acrylate, reacting for 2-24h at 15-60 ℃ to obtain an intermediate; heating to 60-90 ℃, adding polyether/ester dihydric alcohol and a catalyst stannous octoate, and reacting for 1-24h to obtain a polyurethane acrylate prepolymer;

The second method comprises the following steps: reacting diisocyanate and polyether/ester dihydric alcohol at 60-90 ℃ for 1-24h to obtain an intermediate; cooling to 15-60 ℃, adding hydroxyl acrylate and stannous octoate serving as a catalyst, and reacting for 2-24 hours to obtain a polyurethane acrylate prepolymer;

1.2) dissolving the polyurethane acrylate prepolymer, the reactive diluent and the first photoinitiator in a first organic solvent, and stirring at room temperature in the dark for 1-2 hours to form a bottom layer solution, thus obtaining a bottom layer coating; the mass ratio of the polyurethane acrylate to the reactive diluent is 1: 0.1-10; the first photoinitiator accounts for 2-8% of the total mass of the primer after curing, and the first organic solvent accounts for 70-99% of the total mass of the primer;

Second, preparing a top coating

Dissolving a monomer and/or polymer with more than two functional groups capable of performing photopolymerization, a biocompatible hydrophilic polymer and a second photoinitiator in a second organic solvent, and stirring at room temperature in the dark for 1-2 hours to form a surface layer solution, thereby obtaining a surface layer coating; the mass ratio of the monomer with the functional group and/or the polymer to the biocompatible hydrophilic polymer is 1:0.1-10, the mass of the second photoinitiator is 0.5-5% of the total mass of the surface layer coating after curing, and the mass of the second organic solvent is 60-99% of the total mass of the surface layer coating;

The monomer and/or polymer with more than two functional groups capable of carrying out photopolymerization is selected from unsaturated esters and unsaturated ethers including tripropylene glycol diacrylate, polyethylene glycol diacrylate, 1, 6-hexanediol diacrylate, pentaerythritol triacrylate and pentaerythritol tetraacrylate;

Thirdly, preparing a hydrophilic ultra-smooth coating

Coating the primer on the surface of the medical instrument, radiating ultraviolet for 1-60 s, and curing the primer to form a primer on the surface of the medical instrument; coating the surface layer coating on the bottom layer, radiating the surface layer coating for 60-360 seconds by ultraviolet light, and curing the surface layer coating to form a hydrophilic ultra-smooth coating on the surface of the medical instrument; the ultraviolet energy density is 10mw/cm²～120mw/cm²。

3. The method of claim 2, wherein the diisocyanate in the two methods of preparing the urethane acrylate prepolymer in the first step 1.1) comprises: one of 2, 4-toluene diisocyanate, isophorone diisocyanate, hexamethylene-1, 6-diisocyanate, and diphenylmethane diisocyanate; the acrylic acid hydroxyl ester comprises: one or more of hydroxyethyl (meth) acrylate, hydroxypropyl (meth) acrylate and hydroxybutyl (meth) acrylate; the polyether/ester dihydric alcohol comprises: one or more of polyethylene glycol, polypropylene glycol, polytetrahydrofuran diol, polycarbonate diol and polycaprolactone diol, and the number average molecular weight is 200-200000.

4. the method for preparing a hydrophilic ultra-smooth coating according to claim 3, characterized in that the reactive diluent in the first step 1.2) is one or more selected from the group consisting of tripropylene glycol diacrylate, polyethylene glycol diacrylate, 1, 6-hexanediol diacrylate, pentaerythritol triacrylate, and pentaerythritol tetraacrylate.

5. The method of claim 4, wherein the biocompatible hydrophilic polymer in the second step is selected from one or more of polyvinylpyrrolidone, polyvinyl alcohol, polyurethane, polyethylene glycol, sodium polyacrylate, polyacrylamide, sodium polyacrylate-acrylamide moiety, starch, cellulose, alginic acid, hyaluronic acid, chitosan, and collagen, and the number average molecular weight of the hydrophilic polymer is in the range of 2000-5000000.

6. The method for preparing the hydrophilic ultra-smooth coating according to claim 5, wherein the first organic solvent and the second organic solvent are respectively one or more than two selected from ethanol, isopropanol, acetone, butanone and ethyl acetate.

7. the method of claim 6, wherein the first and second photoinitiators are selected from the group consisting of 2-hydroxy-4' (2-hydroxyethoxy) -2-methylpropiophenone, 1-hydroxycyclohexylphenylacetone, 2-hydroxy-2-methyl-1-phenylpropanone, 2-methyl-1- [4- (methylthiophenyl) -2 morpholinyl-1-propanone ], 2-phenylbenzyl-2-dimethylamine-1- (4-morpholinylbenzylphenyl) butanone, phenylbis (2,4, 6-trimethylbenzoyl) phosphine oxide, and benzophenone.

8. The method for preparing the hydrophilic ultra-smooth coating according to claim 7, wherein the coating mode in the third step is a dipping-pulling mode, the dipping time is 1-30s, and the pulling speed is 5-150 mm/min; and thirdly, curing the bottom layer and the surface layer in a rotating mode, wherein the rotating speed is 3-60 rpm/min.