Preparation method of rapid and stable polymer brush coating based on intermediate layer wetting regulation and control

Abstract

The invention belongs to the field of medical care, and provides a preparation method of a rapid and stable polymer brush coating based on intermediate layer wetting regulation, which comprises the following steps: immersing a base material in an organic solution containing a hydrophobic initiator, heating to a preset temperature, and keeping the temperature, so that the hydrophobic initiator enters the base material to obtain the base material with the initiator; dipping the base material with the initiator in a mixed solution of waterborne polyurethane and polyethylene glycol diacrylate, and carrying out photo-initiation polymerization to form a loose WPU / PEGDA layer on the surface of the base material, namely the base material on which the WPU / PEGDA layer grows; and immersing the substrate on which the WPU / PEGDA layer grows into an aqueous solution containing a polymer brush monomer, and carrying out photo-initiation polymerization to form a polymer brush coating, thereby obtaining the polymer brush coating. The prepared polymer brush coating has the advantages of high biocompatibility, strong stability, strong lubricity and adhesion resistance, can be rapidly prepared, and has a huge application prospect in various medical devices.

Description

Technical Field

[0001] The present invention belongs to the field of medical care technology, and specifically relates to a method for preparing a fast and stable polymer brush coating based on intermediate layer wettability regulation, and the application of the coating in medical care fields such as blood contact catheters and urinary catheters. Background Art

[0002] The information disclosed in this background technology section is only intended to enhance the understanding of the overall background of the invention, and should not necessarily be regarded as an admission or any form of suggestion that the information constitutes the prior art already known to a person skilled in the art.

[0003] Implantable medical devices generally face important needs for lubrication and anti-adhesion. For example, in clinical treatment, urinary catheters need to frequently contact body tissues for a long or short period of time. Their weak lubrication properties cause patients to feel varying degrees of burning pain each time they are inserted or removed, which can easily cause corresponding mucosal damage and even tissue inflammation. The non-fouling properties of catheters also make them susceptible to the attachment of adhesins and extracellular polysaccharides, which in turn cause the formation of bacterial aggregates and biofilms, ultimately leading to urinary tract infections in patients. According to statistics, more than 75% of urinary tract infections in nephrology and urology are caused by catheters. In addition, implantable catheters that come into contact with blood are more likely to induce a coagulation response, leading to the formation of thrombosis and related complications. Therefore, efficient and reliable lubrication and anti-adhesion coating technology has attracted widespread attention. Polymer brush coatings are considered to have important prospects for meeting the needs of surface lubrication and anti-adhesion properties by virtue of their controllable chemical configurations and structural properties.

[0004] However, there are still some problems that hinder the application of polymer brush coatings, such as long grafting time and poor stability. Because common medical catheter materials such as polyurethane are highly hydrophobic, during the preparation of polymer brush coatings, it is difficult for hydrophilic polymer brush materials to get close enough to the substrate to initiate growth, which greatly limits the growth rate of the polymer brush and may lead to unevenness of the polymer brush coating. Summary of the invention

[0005] In order to solve the above problems, the present invention provides a fast and stable preparation method of zwitterionic polymer brushes based on the wettability regulation of the intermediate layer. First, the substrate is immersed in an organic solution of a hydrophobic initiator to allow the initiator to enter the interior of the substrate. Then, the substrate is immersed in a mixed solution of waterborne polyurethane and polyethylene glycol diacrylate, and ultraviolet irradiation is initiated to form an intermediate layer on the surface of the substrate, which is entangled with the base network (such as Figure 1 Finally, the substrate with the intermediate layer grown is immersed in an aqueous solution containing polymer brush monomers and irradiated with ultraviolet light to induce the growth of polymer brushes. This method can quickly prepare a stable polymer brush coating.

[0006] In order to achieve the above object, the present invention adopts the following technical solution:

[0007] The first aspect of the present invention provides a method for preparing a fast and stable polymer brush coating based on the wettability regulation of an intermediate layer, comprising:

[0008] The substrate is immersed in an organic solution containing a hydrophobic initiator, heated to a preset temperature and kept warm, so that the hydrophobic initiator enters the interior of the substrate, thereby obtaining a substrate with an initiator;

[0009] The substrate with the initiator is immersed in a mixed solution of waterborne polyurethane and polyethylene glycol diacrylate, and light-initiated polymerization is performed to form a loose WPU / PEGDA layer on the surface of the substrate, that is, a substrate with a WPU / PEGDA layer grown thereon;

[0010] The substrate with the WPU / PEGDA layer grown thereon is immersed in an aqueous solution containing a polymer brush monomer, and light-initiated polymerization is performed to form a polymer brush coating.

[0011] According to the coating bonding theory, the present invention selects water-based polyurethane and polyethylene glycol diacrylate to form an intermediate layer that is entangled with the base network, so that the polymer brush can be quickly and firmly bonded to the base material to obtain strong lubrication performance. Research has found that: compared with other polymer materials, water-based polyurethane and polyurethane substrates have certain similar groups, and the two can be combined more tightly, thereby improving the bonding strength between the water-based polyurethane layer polyethylene glycol diacrylate layer used as a wettability regulator and the substrate. Polyethylene glycol diacrylate has two carbon-carbon double bond structures and can be used as a cross-linking agent to improve the cross-linking strength between the water-based polyurethane and the polyethylene glycol diacrylate layer. On the other hand, the polyethylene glycol structure in polyethylene glycol diacrylate has a strong hydrophilicity, which can improve the wettability of the surface.

[0012] In some embodiments, the substrate is thermoplastic polyurethane or polyetheretherketone.

[0013] In some embodiments, the hydrophobic initiator is selected from at least one of benzophenone, aromatic diazonium salts, and acetophenone derivatives.

[0014] In some embodiments, in the organic solution containing the hydrophobic initiator, the concentration of the hydrophobic initiator is 0.01-0.5 g / mL.

[0015] In some embodiments, the organic solvent is selected from at least one of anhydrous ethanol and acetone.

[0016] In some embodiments, the preset temperature is 40-70°C;

[0017] In some embodiments, the insulation time is 0.2-5h.

[0018] The WPU / PEGDA layer formed by the present invention is entangled with the base network. In order to achieve a better effect, the present invention studies the amount of WPU and PEGDA. In some embodiments, the content of WPU in the mixed solution of waterborne polyurethane and polyethylene glycol diacrylate is 5-40%;

[0019] In some embodiments, the content of PEGDA is 5-40%.

[0020] In some embodiments, the polyethylene glycol diacrylate is selected from at least one of PEGDA200, PEGDA400, and PEGDA600.

[0021] In some embodiments, the synthesis of the WPU / PEGDA layer is performed under ultraviolet light irradiation, the light source is an LED ultraviolet curing lamp, the power is 1000W, and the synthesis time is 5-80 minutes;

[0022] In some embodiments, the polymer brush monomer is selected from at least one of sulfobetaine zwitterionic materials, polyethylene glycol, carboxybetaine zwitterionic materials, phosphorylcholine zwitterionic materials, acrylic acid, and acrylamide.

[0023] In some embodiments, the substrate on which the WPU / PEGDA layer is grown is immersed in an aqueous solution containing a polymer brush monomer and subjected to ultraviolet irradiation to initiate the growth of the polymer brush. The ultraviolet irradiation time is 10-80 minutes.

[0024] In some embodiments, the solution concentration of the polymer brush monomer is 0.01-0.3 g / mL;

[0025] In some embodiments, after the preparation of the polymer brush coating, it needs to be immersed in PBS buffer for 7-10 days, and the PBS solution is replaced every 1-1.5 days to fully remove the initiator and unreacted zwitterionic monomer solution, thereby obtaining a polymer brush coating with high biocompatibility, strong stability, strong lubricity and anti-adhesion.

[0026] The second aspect of the present invention provides a fast and stable polymer brush coating based on the wettability regulation of the intermediate layer prepared by the above method. The method of the present invention can quickly prepare a stable, strong lubricating and anti-adhesive polymer brush coating, which has great application prospects in various medical devices.

[0027] The third aspect of the present invention provides the use of the above-mentioned fast and stable polymer brush coating based on the wettability regulation of the intermediate layer in the preparation of medical catheters or in the biomedical field.

[0028] Beneficial Effects of the Invention

[0029] (1) The preparation method of the polymer brush coating provided by the present invention can rapidly graft highly hydrophilic polymer brushes onto the surface of a hydrophobic substrate, and it takes only about 40 minutes to rapidly reduce the surface water contact angle to 20°.

[0030] (2) The polymer brush coating prepared by the preparation method of the polymer brush coating provided by the present invention has strong stability and can withstand 7 hours of ultrasound without being destroyed.

[0031] (3) The polymer brush coating prepared by the preparation method of the polymer brush coating provided by the present invention has strong lubricating properties. The friction coefficient of the surface after coating modification is as low as 0.0054, achieving a super-slip effect.

[0032] (4) The polymer brush coating prepared by the preparation method of the polymer brush coating provided by the present invention has a strong lubricating property that is sustainable and can maintain a good lubricating effect after repeated wetting and drying.

[0033] (5) The polymer brush coating prepared by the preparation method of the polymer brush coating provided by the present invention has strong anti-adhesion properties and can effectively resist the adhesion of proteins, cells and bacteria.

[0034] (6) The preparation method of the polymer brush coating provided by the present invention has strong universality and can quickly prepare the polymer brush coating on the surface of various substrates. BRIEF DESCRIPTION OF THE DRAWINGS

[0035] The accompanying drawings constituting a part of the present invention are used to provide a further understanding of the present invention, and the exemplary embodiments of the present invention and their description are used to explain the present invention and do not constitute improper limitations on the present invention.

[0036] Figure 1 It is a schematic diagram of the main operation flow of the present invention;

[0037] Figure 2 This is the infrared spectrum test of each stage in the polymer brush modification process of Example 2;

[0038] Figure 3 The water contact angles at various times during the polymer brush modification process of Example 1 and Example 2;

[0039] Figure 4 The stability test results of Example 2 are shown below:

[0040] Figure 5 This is the lubrication effect test of Example 2;

[0041] Figure 6 The change of friction coefficient after ultrasonic and repeated drying in Example 2;

[0042] Figure 7 The protein adhesion test results of the surface of Example 2;

[0043] Figure 8 The protein adhesion test results of the surface of Example 2;

[0044] Fig. 9 The anticoagulant effect of the catheter prepared in Example 3;

[0045] Fig.10 The water contact angles of each surface before and after modification with polymer brush coating in Example 4. DETAILED DESCRIPTION

[0046] It should be noted that the following detailed descriptions are exemplary and are intended to provide further explanation of the present invention. Unless otherwise specified, all technical and scientific terms used in the present invention have the same meanings as those commonly understood by those skilled in the art to which the present invention belongs.

[0047] The present invention will be further described in detail below in conjunction with specific embodiments. It should be noted that the specific embodiments are intended to explain the present invention rather than to limit it.

[0048] In order to realize the construction of the stable hydrated lubricating composite coating of the present invention and the performance of the beneficial effects, the present invention makes Examples 1-4, wherein Example 1 is a conventional photoinitiated polymer brush preparation method as a control example, Example 2 is a polymer brush coating grafted by the present method on a TPU sheet substrate, Example 3 is a TPU catheter grafted with a polymer brush coating by the present method, and Example 4 is a polymer brush coating grafted on the surface of ultra-high molecular weight polyethylene (UMHWPE), polyetheretherketone, (PEEK) polycarbonate (PC), polyvinyl chloride (PVC), and polyoxymethylene (POM) by the present method. The reagents used in the present invention and their abbreviations are as follows: thermoplastic polyurethane (TPU), waterborne polyurethane (WPU), methacryloylethyl sulfobetaine (SBMA), benzophenone (BP), polyethylene glycol diacrylate (PEGDA400).

[0049] In the following examples, the sulfobetaine zwitterionic material monomer is SBMA.

[0050] Example 1

[0051] In this embodiment, a conventional method for preparing a photoinitiated polymer brush is provided as a control example for the following embodiments. The specific preparation scheme is to immerse the TPU in a 0.2 g / mL BP anhydrous ethanol solution, heat it to 55°C, and keep it warm for 5 hours. Then, the TPU substrate with BP is immersed in an aqueous solution containing 0.1 g / mL of sulfobetaine zwitterionic material monomer for ultraviolet irradiation, thereby initiating the growth of the polymer brush. The light source is an LED ultraviolet curing lamp with a power of 1000 W, and the irradiation time is 0.5, 1, 2, 3, 4, 5, and 6 hours, respectively.

[0052] Example 2

[0053] This example provides an example of a polymer brush prepared by the method of the present invention.

[0054] The specific method is to immerse a sheet (3cm*3cm*0.2cm) of TPU into a 0.2g / mL BP anhydrous ethanol solution, heat it to 55°C, and keep it warm for 5 hours to allow the hydrophobic initiator to enter the interior of the substrate.

[0055] The TPU substrate with BP was then immersed in a mixed aqueous solution of WPU and PEGDA, where the content of WPU and PEGDA was 15%. UV irradiation was then performed to form a loose WPU / PEGDA layer on the surface of the substrate, which was entangled with the base network. The UV irradiation time was 10 minutes.

[0056] Finally, the substrate with the WPU / PEGDA layer grown was immersed in an aqueous solution containing 0.1 g / mL of sulfobetaine zwitterionic material monomer for ultraviolet irradiation to induce the growth of polymer brushes. The light source was an LED ultraviolet curing lamp with a power of 1000 W, and the irradiation time was 5, 10, 20, 30, 40, 50, and 60 minutes, respectively.

[0057] Example 3

[0058] The specific method is to immerse a TPU catheter with an inner diameter of 1.4 mm into a BP anhydrous ethanol solution with a content of 0.2 g / mL, heat it to 55°C, and keep it warm for 5 hours to allow the hydrophobic initiator to enter the interior of the substrate.

[0059] The TPU catheter with BP was then immersed in a mixed aqueous solution of WPU and PEGDA, wherein the content of WPU and PEGDA was 15%. UV irradiation was then performed to form a loose WPU / PEGDA layer on the surface of the substrate, which was entangled with the base network. The UV irradiation time was 10 minutes.

[0060] Finally, the TPU catheter with the WPU / PEGDA layer grown on it was immersed in an aqueous solution containing 0.1 g / mL of sulfobetaine zwitterionic material monomer for ultraviolet irradiation to induce the growth of the polymer brush. The light source was an LED ultraviolet curing lamp with a power of 1000 W and the irradiation time was 60 minutes.

[0061] Example 4

[0062] The method is used to brush the polymer grafted on the surface of ultra-high molecular weight polyethylene (UMHWPE), polyetheretherketone (PEEK), polycarbonate (PC), polyvinyl chloride (PVC), and polyoxymethylene (POM).

[0063] The specific method is to immerse a sheet-shaped (3cm*3cm*0.2cm) substrate into a 0.2g / mL BP anhydrous ethanol solution, heat it to 55°C, and keep it warm for 5 hours to allow the hydrophobic initiator to enter the interior of the substrate.

[0064] The substrate with BP was then immersed in a mixed aqueous solution of WPU and PEGDA, where the content of WPU and PEGDA was 15%. UV irradiation was then performed to form a loose WPU / PEGDA layer on the surface of the substrate, which was entangled with the base network. The UV irradiation time was 10 minutes.

[0065] Finally, the substrate with the WPU / PEGDA layer grown was immersed in an aqueous solution containing 0.1 g / mL of sulfobetaine zwitterionic material monomer for ultraviolet irradiation to induce the growth of the polymer brush. The light source was an LED ultraviolet curing lamp with a power of 1000 W and the irradiation time was 60 minutes.

[0066] Characterization methods:

[0067] Fourier infrared spectroscopy test: Fourier infrared spectroscopy test was performed on the sample in the grafting process of Example 2, wherein PSBMA is the sample obtained when the irradiation time in Example 2 is 60 minutes. Figure 2 As shown in the figure, after the WPU / PEGDA layer grows on the TPU surface, the substrate surface is at 2916 cm -1 A characteristic peak appeared at 1660 cm -1 The characteristic peak at 1038.5 cm indicates that WPU is fixed on the surface. After PSBMA polymer brush grafting, quaternary amine groups and sulfonic acid groups are introduced. -1 This proves that the PSBMA polymer brush coating can be prepared on the surface of TPU substrate by this method, and the preparation process is in line with expectations.

[0068] Comparison of polymer brush grafting speed: The changes in the surface water contact angle during the preparation of SBMA polymer brushes at different irradiation times in Example 1 and Example 2 were recorded respectively. Figure 3 As shown, in Example 1, the initiation grafting speed of PSBMA is slow after the BP initiator is embedded in the TPU surface. The water contact angle of the surface can only be reduced to about 20° after 6 hours of ultraviolet irradiation. In Example 2, after a loose WPU / PEGDA layer is formed on the surface, the grafting speed of the PSBMA polymer brush is significantly improved, and the surface water contact angle can be reduced to 20° within 40 minutes, which is nearly 90% faster. This proves that the grafting of the PSBMA polymer brush based on the WPU / PEGDA layer to regulate the wetting gradient proposed in this method can significantly reduce the grafting time.

[0069] Stability test: The coatings prepared in Example 1 and Example 2 were immersed in deionized water for ultrasonic treatment (power of 360W), and the amount of SBMA released in the deionized water was detected. Figure 4 As shown in Figure 2, the polymer brush coating of Example 2 (irradiation time is 60 minutes) has a shedding amount of less than 7.5 ug / cm during 7 hours of ultrasound. 2 , and after 3 hours, the shedding amount almost stopped increasing. In contrast, the shedding amount of the polymer brush coating in Example 1 (irradiation time was 6 hours) continued to increase, reaching 20ug / cm after 7 hours of ultrasound. 2 .

[0070] Friction test: A friction test was conducted using a rheometer at a normal force of 1 N and a shear rate of 30 r / min to obtain the friction force and define the effective friction coefficient to characterize the lubrication effect of each embodiment. Figure 5 As shown, the friction coefficient of the TPU surface is 0.2678. The grafting of the PSBMA polymer brush in Example 2 leads to a rapid decrease in the friction coefficient. In Example 2, the friction coefficient of the PSBMA polymer brush coating with a grafting time of 20 minutes is reduced to 0.0715, while the friction coefficient of the PSBMA polymer brush coating with a grafting time of 40 minutes is reduced to about 0.01, and the lubrication effect is good.

[0071] Lubrication stability test: The coating prepared in Example 2 (irradiation time of 60 minutes) was repeatedly dried (10 times) and ultrasonically treated (360W, 7h), and then the friction coefficient was measured using a rheometer at a normal force of 0.5N and a shear rate of 30r / min. The results are shown in Figure 2. Figure 6 As shown, neither ultrasonic treatment nor repeated drying can significantly increase the friction coefficient of Example 2.

[0072] Anti-protein adhesion test: Protein adhesion test was performed on the coating prepared in Example 2 (irradiation time was 60 minutes) and TPU material using proteins such as fibrinogen, bovine serum albumin, and lysozyme. Figure 7 As shown, the amount of protein adhesion on the surface of Example 2 is much lower than that on the TPU surface.

[0073] Protein adhesion test: A fibrinogen-modified AFM probe was used to test the protein adhesion of the coating prepared in Example 2 (irradiation time was 60 minutes) and the TPU surface. Figure 8 As shown, the protein adhesion of the surface of Example 2 is much lower than that of the TPU surface.

[0074] Coating application test: The coated catheter prepared in Example 3 and the uncoated catheter were subjected to a blood circulation test. The blood source was commercially available anticoagulated pig blood (sodium citrate anticoagulation blood collection tubes were used to collect fresh pig blood at a ratio of 1:9). Before the blood circulation test, the anticoagulated pig blood was calcified to restore its coagulation properties. The calcification operation was to add calcium chloride to the anticoagulated pig blood, and the amount added was added at a ratio of anticoagulated pig blood: 1M calcium chloride solution = 100:5. A peristaltic pump was used during the test, with a rotation speed of 20 rpm and an average blood flow rate of 6 cm / s in the tube.

[0075] Test results such as Fig. 9 As shown, many adherent clots formed on the inner wall of the uncoated TPU tube after 4 hours of blood circulation. In contrast, the catheter of Example 3 modified by the PSBMA polymer brush coating grafted by the WPU / PEGDA layer remained unobstructed and no thrombus was observed. It can also be found in the SEM image that the surface of the catheter of Example 3 with coating is smooth, while the surface of the uncoated TPU tube has been covered with a large number of thrombi. This shows that the coating preparation method provided by the present invention can make the surface have an excellent lubricating effect, and can also effectively resist the adhesion of blood components such as proteins and platelets, thereby achieving an anti-coagulation effect.

[0076] Study on the universality of the coating preparation method. In Example 4, the water contact angle of the substrate before and after coating preparation was tested. The results are shown in Fig.10 As shown in the figure, the surface wettability of each substrate is significantly improved after coating modification, and the water contact angle is generally reduced by about 60°.

[0077] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. For those skilled in the art, the present invention may have various modifications and variations. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention shall be included in the protection scope of the present invention.

Claims

1. A method for preparing a fast and stable polymer brush coating based on intermediate layer wettability regulation, characterized in that: include: The substrate is immersed in an organic solution containing a hydrophobic initiator, heated to a preset temperature and kept warm, so that the hydrophobic initiator enters the interior of the substrate, thereby obtaining a substrate with an initiator; The substrate with the initiator is immersed in a mixed solution of waterborne polyurethane and polyethylene glycol diacrylate, and light-initiated polymerization is performed to form a loose WPU / PEGDA layer on the surface of the substrate, that is, a substrate with a WPU / PEGDA layer grown thereon; The substrate with the WPU / PEGDA layer grown thereon is immersed in an aqueous solution containing a polymer brush monomer, and light-initiated polymerization is performed to form a polymer brush coating.

2. The method for preparing a fast and stable polymer brush coating based on intermediate layer wettability control according to claim 1, characterized in that: The substrate is thermoplastic polyurethane or polyetheretherketone.

3. The method for preparing a fast and stable polymer brush coating based on intermediate layer wettability control according to claim 1, characterized in that: The hydrophobic initiator is selected from at least one of benzophenone, aromatic diazonium salts and acetophenone derivatives.

4. The method for preparing a fast and stable polymer brush coating based on intermediate layer wettability control according to claim 1, characterized in that: In the organic solution containing the hydrophobic initiator, the concentration of the hydrophobic initiator is 0.01-0.5 g / mL.

5. The method for preparing a fast and stable polymer brush coating based on intermediate layer wettability control according to claim 1, characterized in that: The preset temperature is 40-70°C; Or, the insulation time is 0.2-5h.

6. The method for preparing a fast and stable polymer brush coating based on intermediate layer wettability control according to claim 1, characterized in that: In the mixed solution of waterborne polyurethane and polyethylene glycol diacrylate, the content of WPU is 5-40%; Alternatively, the content of PEGDA is 5-40%.

7. The method for preparing a fast and stable polymer brush coating based on intermediate layer wettability control according to claim 1, characterized in that: The polymer brush monomer is selected from at least one of sulfobetaine zwitterionic materials, polyethylene glycol, carboxybetaine zwitterionic materials, phosphorylcholine zwitterionic materials, acrylic acid, and acrylamide.

8. The method for preparing a fast and stable polymer brush coating based on intermediate layer wettability control according to claim 1, characterized in that: The solution concentration of the polymer brush monomer is 0.01-0.3 g / mL; Alternatively, after the polymer brush coating is prepared, it needs to be immersed in PBS buffer for 7-10 days, and the PBS solution is replaced every 1-1.5 days.

9. A fast and stable polymer brush coating based on intermediate layer wettability regulation prepared by the method described in any one of claims 1 to 8.

10. Use of the fast and stable polymer brush coating based on intermediate layer wettability regulation as claimed in claim 9 in the preparation of medical catheters or in the biomedical field.

Images