CN114432505A

CN114432505A - Polyurethane material with composite water-wet coating and application thereof in interventional therapy field

Info

Publication number: CN114432505A
Application number: CN202210170150.1A
Authority: CN
Inventors: 满佳; 宋鑫忠; 张永琪; 李建勇; 李剑峰
Original assignee: Shandong University
Current assignee: Shandong University
Priority date: 2022-02-23
Filing date: 2022-02-23
Publication date: 2022-05-06
Anticipated expiration: 2042-02-23
Also published as: CN114432505B

Abstract

The invention relates to a polyurethane material with a composite water-wet coating and application thereof in the field of interventional therapy. The invention provides a method for constructing a stable composite water-wet coating on the surface of polyurethane, wherein the composite water-wet coating comprises a polydopamine-natural polymer layer and a zwitter-ion lubricating layer, and the preparation method comprises the following steps: (1) performing low-temperature plasma treatment on polyurethane to activate the surface; (2) dissolving dopamine and natural macromolecules in a trihydroxymethyl aminomethane buffer solution to serve as a modified solution, and then immersing the activated polyurethane in the modified solution to construct a polydopamine-natural macromolecule layer; (3) the modified polyurethane of the invention is ultrasonically cleaned by deionized water, the surface wettability of the modified polyurethane is obviously improved, the friction coefficient is effectively reduced, the leaching stability is good, and the modified polyurethane has great application potential in the field of biomedicine.

Description

Polyurethane material with composite water-wet coating and application thereof in interventional therapy field

Technical Field

The invention belongs to the technical field of interventional medical instruments, and particularly relates to a polyurethane material with a composite water-wet coating, a preparation method of the material and application of the material in the field of interventional therapy.

Background

The information in this background section is only for enhancement of understanding of the general background of the invention and is not necessarily to be construed as an admission or any form of suggestion that this information forms the prior art that is already known to a person of ordinary skill in the art.

In recent years, the rapid development of interventional therapy is the third most rapidly developed medical science after internal medicine and surgery, and the third most rapidly developed medical science makes up for the defects of internal and surgical technologies. Interventional therapy is a novel high-tech minimally invasive treatment technology, has the characteristics of small wound, multiple indications, definite curative effect, quick postoperative recovery and the like, and is an important development trend of future medicine. Interventional therapy is usually conducted by introducing a specific instrument into a diseased part of a human body through a natural duct or a tiny wound of the human body by using a puncture needle, a catheter and other interventional devices under the guidance and monitoring of an imaging device such as a digital subtraction angiography machine, a CT, ultrasound, magnetic resonance and the like. The vascular interventional therapy has wide application in the fields of intravascular specimen taking, angiography technology, local embolism and thrombus clearing, intravascular medicine perfusion, intravascular dilation forming intravascular stent implantation, intravascular vein filter implantation and the like. The problems of difficult catheter insertion, large resistance and the like exist in the vascular interventional operation, which are caused by poor wettability and poor friction performance of the polyurethane surface, so that the polyurethane surface with high wettability and low friction needs to be explored and constructed to expand the application field of the vascular interventional treatment and improve the safety of the interventional operation.

The construction of hydrophilic coating on the surface of interventional catheter is an effective strategy for improving wettability and reducing friction coefficient, and the existing improvement mode is as follows: (1) a layer of hydrogel coating is constructed on the surface of the catheter, but the hydrogel coating absorbs water and expands, is not suitable for a thin catheter, and has weak strength and easy shedding; (2) a hydrophilic polymer coating is constructed on the surface of the catheter by a physical and chemical adsorption method, but the coating is unstable and has poor bearing capacity; (3) the polymer molecular brush is grafted on the surface of the catheter, but the lubricating effect depends on the grafting density and the length of the polymer molecular brush, and the lubricating effect of the molecular brush on a macroscopic level is not ideal, so that the current research direction is to construct a composite lubricating coating, but the requirements of low friction, high load bearing and high stability cannot be met.

Inspired by mussels that adsorb strongly to moist surfaces, dopamine, which undergoes oxidation in alkaline solution to form complex polydopamine structures and deposits on the surface to form strong covalent and non-covalent interactions with the substrate, without expensive instruments, without complex steps and without limitations of the nature of the substrate, has a variety of functional groups, allowing further modification, has become a research focus as a new coating and binder material. Sodium alginate, also known as algin, is a natural high-molecular polysaccharide extracted from deep-sea brown algae, chitosan, also known as chitosan, is obtained by deacetylation of chitin widely existing in the nature, and has good biocompatibility and environmental protection performance, and wide application prospect in the field of biomedicine. The sulfobetaine type zwitterion has good biocompatibility, contamination resistance and wettability, and a layer of water molecule can be directionally fixed in an aqueous solution through electrostatic force and hydrogen bond energy to form a hydration membrane.

Disclosure of Invention

The invention provides a polyurethane material with a composite wet coating, wherein a natural high polymer material is fixed on the surface of polyurethane by utilizing dopamine, and then methacrylamide ethyl sulphobetaine is grafted to form the composite lubricating coating, so that the composite lubricating coating has extremely low friction coefficient, high leaching stability and strong bearing capacity, and can meet the practical application.

Based on the technical effects, the invention provides the following technical scheme:

in a first aspect of the invention, a polyurethane material with a composite water-wet coating is provided, wherein the composite water-wet coating at least comprises a polydopamine-natural polymer layer; the polydopamine-natural polymer layer is formed by connecting dopamine and natural polymers and is connected with a polyurethane material through the dopamine.

In a preferred embodiment of the first aspect, the composite water-wet coating layer further includes a zwitterionic lubricating layer formed by an arrangement of sulfobetaine zwitterionic molecular brushes, and is connected to the natural polymer through a carbon-carbon single bond.

In a second aspect of the present invention, a preparation method of the polyurethane material with the composite water-wet coating layer in the first aspect is provided, and the preparation method comprises the following steps: the method comprises the steps of treating polyurethane by using plasma for surface activation, soaking the activated polyurethane in a buffer solution of dopamine and natural macromolecules, adding a catalyst, and supplementing oxygen to deposit a dopamine-natural macromolecule layer on the surface of the polyurethane.

Firstly, in the second aspect, the barrier medium for plasma treatment is helium, the polyurethane material is modified for 15-30min under the condition of pure helium environment, and hydroxyl is introduced on the surface of the polyurethane material to be used as a subsequent reaction site; further, the voltage amplitude of the plasma processing equipment is 3-8 KV, the voltage frequency is 30-50 KHz, the duty ratio is 25% -55%, and the modulation frequency is 80-120 Hz.

Secondly, in the preparation of the natural polydopamine polymer layer according to the second aspect, the natural polymer is natural polysaccharide, preferably chitosan, a chitosan derivative or alginate; specific examples are carboxymethyl chitosan or sodium alginate; wherein the adding ratio of the dopamine to the natural polymer is 1-3: 3 to 8.

In the above preferred embodiment, the catalyst is 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide; one example of such a means of oxygen replenishment is pumping.

Based on the above preferred embodiment, the preparation of the polydopamine-natural polymer layer comprises the following specific steps:

soaking the activated polyurethane material in 1-3 mg/mL dopamine and 3-8 mg/mL carboxymethyl chitosan or sodium alginate trihydroxymethyl aminomethane-hydrochloric acid buffer solution, adjusting the pH value to 8-9 by using 1- (3-dimethylaminopropyl) -3-ethyl carbodiimide as a catalyst, and soaking for 12-48 hours at room temperature while continuously pumping oxygen vibration.

Preferably, after the preparation of the poly-dopamine-natural polymer layer is finished, the dopamine and natural polymer adsorbed on the surface of the film are also required to be removed by cleaning; specifically, the ultrasonic cleaning is performed for 30 seconds, and repeated cleaning can be performed as many times as required.

The deposition of the polydopamine-natural polymer layer can assist in improving the surface smoothing effect of the polyurethane material, and the plasma treatment plays an important role in obtaining the smooth surface. In addition, in order to obtain a denser and firmer lubricating layer, the poly-dopamine-natural polymer layer is further connected with a zwitterion lubricating layer; is formed by arranging sulfobetaine type zwitterionic molecular brushes in the following preparation mode:

and (3) immersing the polyurethane material deposited with the polydopamine-natural high molecular layer into methacryloyl ethyl sulfobetaine solution, taking ammonium ceric nitrate as an oxidation catalyst, and grafting and growing for 12-48 hours at the temperature of 45-65 ℃.

Further, the methacryl ethyl sulfobetaine solution is an aqueous solution, and the concentration is 0.01-0.2 g/mL.

Further, the grafting temperature is 50-60 ℃, and the grafting growth time is 20-28 hours.

Further, the oxidation catalyst also comprises concentrated nitric acid.

In a third aspect of the invention, the polyurethane material with the composite water-wet coating layer of the first aspect is provided for application in the field of interventional therapy.

Preferably, the application includes but is not limited to the use of the polyurethane material with the composite water-wet coating layer in the first aspect for preparing medical devices in the field of interventional therapy; further, the medical device is made of polyurethane, and specific examples include an interventional catheter, an interventional polyurethane stent and the like.

The beneficial effects of one or more technical schemes are as follows:

(1) according to the invention, active groups such as hydroxyl groups are introduced on the surface of the substrate through low-temperature plasma treatment, so that the polydopamine-natural polymer layer is more bonded with the substrate in a covalent bond mode, and the whole lubricating coating is more stable and firm.

(2) The bionic mussel dopamine adhesive fixes a natural high polymer material rich in hydroxyl on the surface of a substrate to serve as a buffer layer, bears high load, exposes polyhydroxy radicals on the surface, increases the growth density of a subsequent polyampholytic molecular brush, and improves the hydration lubrication effect.

(3) The densely grafted sulfobetaine type zwitterionic molecular brush has strong hydration, water molecules are directionally arranged inside and on the surface of a lubricating layer through electrostatic force and hydrogen bonds to form a firm hydrated lubricating layer, the friction coefficient is effectively reduced, and fibrinogen and nonspecific protein adsorption are resisted.

(4) The friction coefficient of the interventional polyurethane surface composite water lubricating coating constructed by the invention is as low as 0.03, and the interventional polyurethane surface composite water lubricating coating has the advantages of high bearing capacity and strong stability; the low friction coefficient is kept under the pressure of 0.6N, and the defects of poor wettability and high friction coefficient of the surface of the substrate are overcome; the leaching stability is good, the leaching rate is low, the leaching rate in 14 days is 0.2%, and the long-acting lubrication effect is kept; resisting the adsorption of fibrinogen and nonspecific protein, having certain antibacterial property, and ensuring the safety of clinical application.

Drawings

The accompanying drawings, which are incorporated in and constitute a part of this specification, are included to provide a further understanding of the invention, and are incorporated in and constitute a part of this specification, illustrate exemplary embodiments of the invention and together with the description serve to explain the invention and not to limit the invention.

Fig. 1 is a schematic diagram of a dopamine grafting process in the composite water-based coating according to the present invention.

FIG. 2 is a schematic diagram of the grafting process of the natural polymer in the composite water-wet coating according to the present invention.

FIG. 3 is a schematic diagram of a process for grafting a zwitterionic molecular brush in the composite water-based coating according to the invention.

FIG. 4 is a surface morphology of a hydrated lubricating coating modified intervening polyurethane of examples 1-8.

Fig. 5 shows the contact angle changes of examples 1 to 8.

FIG. 6 is a Fourier IR spectrum of the surface of the hydrated lubricating coating of examples 1-8 showing grafting.

FIG. 7 is an X-ray photoelectron spectrum of the surface of the hydrated lubricating coating of examples 1 to 8 showing the effect of grafting.

Fig. 8 is a graph showing the effect of the experiment on the leaching stability of the modified intervening polyurethane of the hydrated lubricating coating in examples 1 to 8.

Fig. 9 is a graph of the results of the friction experiments with the modified intervening polyurethane of the hydrated lubricating coatings of examples 1-8.

Detailed Description

It is to be understood that the following detailed description is exemplary and is intended to provide further explanation of the invention as claimed. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs.

It is noted that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of exemplary embodiments according to the invention. As used herein, the singular forms "a", "an" and "the" are intended to include the plural forms as well, and it should be understood that when the terms "comprises" and/or "comprising" are used in this specification, they specify the presence of stated features, steps, operations, devices, components, and/or combinations thereof, unless the context clearly indicates otherwise.

In order to make the technical solutions of the present invention more clearly understood by those skilled in the art, the technical solutions of the present invention will be described in detail below with reference to specific embodiments.

In order to realize the construction of the stable hydrated lubricating composite coating and the expression of the beneficial effects, the invention is shown in the embodiment 1 to the embodiment 8, wherein the embodiment 7 and the embodiment 8 respectively adopt sodium alginate and carboxymethyl chitosan as natural polymers to construct the stable hydrated lubricating composite coating for the interventional catheter, and the other embodiments are comparative examples. The reagents used in the invention and the abbreviations are as follows: methacryloyl ethyl Sulfobetaine (SBMA), Ceric Ammonium Nitrate (CAN), dopamine hydrochloride (DPA), Tris (hydroxymethyl) aminomethane (Tris), Sodium Alginate (SA), carboxymethyl chitosan (CMC), 1- (3-dimethylaminopropyl) -3-ethyl carbodiimide hydrochloride (EDC), concentrated nitric acid, wherein CAN and concentrated nitric acid are used as oxidation catalysts for zwitter-ion grafting, EDC is used as a catalyst for Michael addition reaction between dopamine and natural polymer materials, Tris is used for preparing a buffer solution for dissolving dopamine hydrochloride, and 1mol/L hydrochloric acid and sodium hydroxide are used for adjusting pH.

Example 1

In this example, an untreated thermoplastic polyurethane is provided as a blank control for the following example, based on an intervening thermoplastic polyurethane, pretreated as follows: cutting a 2 x 2 cm sample, ultrasonically cleaning the sample with acetone and absolute ethyl alcohol respectively, and then soaking the sample in absolute ethyl alcohol and deionized water respectively for 12 hours.

The following schemes in the examples are all carried out on the surface of the polyurethane material provided in the examples.

Example 2

(1) Under the argon atmosphere, the voltage is 5000V, the pulse frequency is 100Hz, the pulse duty ratio is 30 percent, the plasma is treated for 20 minutes, and hydroxyl active groups are introduced on the surface of the substrate.

(2) 80mL of water is measured, 8g of SBMA, 0.08g of CAN and 0.2g of concentrated nitric acid are added, the mixture is soaked for 24 hours at the temperature of 55 ℃, and the mixture is washed by deionized water for multiple times.

Example 3

(1) 80mL of water, 0.097g of Tris, hydrochloric acid to adjust the pH to 8.5, 0.19g of DPA, 0.4g of sodium alginate, 0.14g of 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride (EDC) are measured, placed at room temperature for 24 hours, washed in an ultrasonic bath with a large amount of deionized water for 30 seconds, and dried in vacuum, wherein the dopamine undergoes a Michael addition reaction with the sodium alginate in an alkaline environment and is deposited on the surface of a substrate.

Example 4

(1) 80mL of water, 0.097g of Tris, hydrochloric acid to adjust pH to 8.5, 0.19g of DPA, 0.4g of carboxymethyl chitosan, 0.14g of 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride (EDC) were measured, left at room temperature for 24 hours, washed in an ultrasonic bath with a large amount of deionized water for 30 seconds, and vacuum-dried, in which step dopamine undergoes a Michael addition reaction with carboxymethyl chitosan in an alkaline environment and is deposited on the surface of a substrate.

Example 5

(2) 80mL of water, 0.097g of Tris, hydrochloric acid to adjust the pH to 8.5, 0.19g of DPA, 0.4g of sodium alginate, 0.14g of 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride (EDC) are measured, placed at room temperature for 24 hours, washed in an ultrasonic bath with a large amount of deionized water for 30 seconds, and dried in vacuum, wherein the dopamine undergoes a Michael addition reaction with the sodium alginate in an alkaline environment and is deposited on the surface of a substrate.

Example 6

(2) 80mL of water, 0.097g of Tris, hydrochloric acid to adjust pH to 8.5, 0.19g of DPA, 0.4g of carboxymethyl chitosan, 0.14g of 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride (EDC) were measured, left at room temperature for 24 hours, washed in an ultrasonic bath with a large amount of deionized water for 30 seconds, and vacuum-dried, in which step dopamine undergoes a Michael addition reaction with carboxymethyl chitosan in an alkaline environment and is deposited on the surface of a substrate.

Example 7

(3) 80mL of water is measured, 8g of SBMA, 0.08g of CAN and 0.2g of concentrated nitric acid are added, the mixture is soaked for 24 hours at the temperature of 55 ℃, and the mixture is washed by deionized water for multiple times.

Example 8

The characterization method comprises the following steps:

coating characterization experiment: and (3) performing X-ray photoelectron spectroscopy (XPS) and Fourier infrared spectroscopy (FTIR) experiments to characterize the grafting condition of the lubricating coating on the surface of the substrate. As shown in an X-ray photoelectron spectroscopy (XPS) chart of FIG. 7, the examples 2, 3, 4, 7 and 8 have characteristic peaks of sulfur element at 167.7eV of binding energy, and the examples 2, 3, 4, 7 and 8 have characteristic peaks of S ═ O double bond at 1038cm-1 in a Fourier infrared spectrum chart of FIG. 6, so that the grafting of the methacrylethyl sulfobetaine of the examples 2, 3, 4, 7 and 8 is proved to be successful.

Surface wettability characterization experiment: the contact angle of the embodiment is measured by about 3-4 mu L of deionized water, and the wettability change before and after the lubricating coating is modified is represented. As shown in fig. 5, the wettability of each sample was improved after surface modification, with the wettability being the best in example 7.

Surface topography characterization experiment: and detecting the surface appearance and calculating the roughness of each embodiment by using a white light interferometer, and representing the surface appearance change before and after the lubricating coating is modified. As shown in fig. 4, in examples 5 and 6, which are coatings of dopamine with carboxymethyl chitosan and sodium alginate, respectively, the subsequent non-grafted zwitterion has a reduced surface roughness, indicating that dopamine and intermediates tend to form a thin and uniform coating on the surface, and the roughness generally increases after grafting zwitterion.

Stability test: and (3) taking a sample and soaking the sample in a PBS buffer solution for 14 days, and detecting the concentration of the leached zwitterion by using an ultraviolet spectrophotometer so as to represent the stability of the methacryloyl ethyl sulfobetaine in the lubricating coating. As shown in FIG. 8, example 2 is a conventional grafting method with low stability and much higher leaching rate than the composite coating of the present invention, and in addition, the stability of the composite coatings of examples 7 and 8 after plasma treatment is improved to a certain extent compared with the composite coatings without plasma treatment.

Friction test: in a friction and wear test with a normal force of 2N, the friction force is obtained, the effective friction coefficient is defined, and the surface lubrication effect is represented, as shown in FIG. 9, the long-acting friction coefficient of example 7 is lower and lower than that of the existing grafting mode.

The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention, and various modifications and changes may be made by those skilled in the art. Any modification, equivalent replacement, or improvement made within the spirit and principle of the present invention should be included in the protection scope of the present invention.

Claims

1. The polyurethane material with the composite water-wet coating is characterized in that the composite water-wet coating is a polydopamine-natural polymer layer, is formed by connecting dopamine and polymers and is connected with polyurethane through the dopamine.

2. The polyurethane material with the composite water-wet coating layer according to claim 1, wherein the composite water-wet coating layer further has a zwitterionic lubricating layer, and the zwitterionic lubricating layer is formed by arranging sulfobetaine type zwitterionic molecular brushes and is connected with the natural macromolecules through carbon-carbon single bonds.

3. The method for preparing the polyurethane material with the composite water-wet coating according to claim 1 or 2, wherein the preparation method comprises the steps of carrying out surface activation by treating polyurethane with plasma, soaking the activated polyurethane in a buffer solution of dopamine and natural macromolecules, adding a catalyst and supplementing oxygen to deposit a dopamine-natural macromolecule layer on the surface of the polyurethane.

4. The method for preparing the polyurethane material with the composite water-wet coating according to claim 3, wherein the ionization blocking medium of the plasma is helium, and the surface activation time is 15-30 min; the voltage amplitude of the plasma processing equipment is 3-8 KV, the voltage frequency is 30-50 KHz, the duty ratio is 25% -55%, and the modulation frequency is 80-120 Hz.

5. The method for preparing the polyurethane material with the composite water-wet coating according to claim 3, wherein the natural polymer is carboxymethyl chitosan or sodium alginate; wherein the adding ratio of the dopamine to the natural polymer is 1-3: 3 to 8.

6. The method for preparing the polyurethane material with the composite water-wet coating according to claim 3, wherein the catalyst is 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide; the oxygen is supplemented by pumping.

7. The method for preparing the polyurethane material with the composite water-wet coating according to any one of claims 3 to 6, wherein the poly-dopamine-natural polymer layer is prepared by the following specific steps:

soaking the activated polyurethane in a trihydroxymethyl aminomethane-hydrochloric acid buffer solution of 1-3 mg/mL dopamine and 3-8 mg/mL carboxymethyl chitosan or sodium alginate, adjusting the pH to 8-9 by using 1- (3-dimethylaminopropyl) -3-ethyl carbodiimide as a catalyst, and soaking for 12-48 hours at room temperature while continuously pumping oxygen vibration.

8. The method for preparing the polyurethane material with the composite water-wet coating according to claim 3, wherein the polydopamine-natural polymer layer is further provided with a zwitterionic lubricating layer which is formed by arranging sulfobetaine type zwitterionic molecular brushes, and the method for preparing the polyurethane material with the composite water-wet coating is as follows:

9. The method for preparing the polyurethane material with the composite water-wet coating according to claim 8, wherein the methacrylethyl sulfobetaine solution is an aqueous solution, and the concentration of the methacrylethyl sulfobetaine solution is 0.01-0.2 g/mL;

or the grafting temperature is 50-60 ℃, and the grafting growth time is 20-28 hours;

alternatively, the oxidation catalyst further comprises concentrated nitric acid.

10. The application of the polyurethane material with the composite water-wet coating layer in the field of interventional therapy, which is characterized in that the polyurethane material with the composite water-wet coating layer in the claim 1 or 2 is used for preparing a medical device in the field of interventional therapy; the medical apparatus is an interventional catheter or an interventional polyurethane stent.