Polymer product coated with hydrogel layer on surface as well as preparation method and application of polymer product

Abstract

The invention relates to the technical field of polymers, and provides a polymer product coated with a hydrogel layer on the surface as well as a preparation method and application of the polymer product. The polymer product with the surface coated with the hydrogel layer comprises a polymer base material and the hydrogel layer coated on the surface of the polymer base material, the hydrogel layer comprises a natural polymer cross-linked network, and the natural polymer cross-linked network is formed by cross-linking polymerizable natural polymers grafted on the surface of the polymer base material. According to the polymer product with the surface coated with the hydrogel layer, the surface of the polymer base material is coated with the hydrogel layer which is uniform in thickness and excellent in biocompatibility, and the polymer product can be used in the field of preparation of medical instruments with high requirements for lubricating performance.

Description

Technical Field

[0001] The present invention relates to the technical field of polymers, and more specifically, to a polymer article with a hydrogel layer coated on its surface, a preparation method thereof, and an application thereof. Background Art

[0002] Polymer materials usually have excellent mechanical properties and weather resistance and are also widely used in the field of medical materials. However, their lubricity and biocompatibility are poor, which can cause pain and rejection reactions to patients. To improve the lubricity of medical devices, a hydrogel or polymer coating can be coated on the surface of the medical device by dipping, spraying, etc. to obtain a super-slippery surface. In addition, active substances such as noble metals, metal oxides, and antibacterial peptides can be embedded in the hydrogel or polymer coating to achieve the purpose of antibacterial. However, the mechanical strength of the coating obtained by physical methods and the bonding strength with the substrate are not high enough. In recent years, the method of modifying the surface of medical devices by chemical grafting has received extensive attention. The chemical grafting method uses an initiator embedded on the surface of the substrate to initiate the polymerization of hydrophilic monomers on the surface of the substrate, and a relatively thin hydrogel coating can be obtained to improve the lubricity and encapsulate a small amount of antibacterial agent or drug. Commonly used hydrophilic monomers are acrylamide and acrylic acid, which have relatively large biological toxicity and are not easy to be completely removed when remaining in the hydrogel. In addition, medical devices often have precise and complex structures, and it is difficult to prepare a hydrogel coating with a uniform thickness on a complex surface through a mold. Therefore, how to prepare a hydrogel coating with high bonding strength, good biocompatibility, and uniform thickness on the surface of medical devices with any shape is still a major challenge. Summary of the Invention

[0003] The purpose of the present invention is to provide a polymer article with a hydrogel layer coated on its surface and a preparation method thereof, so as to solve the technical problems in the prior art that it is difficult to prepare a hydrogel coating with a uniform thickness on the surface of polymer articles with any shape and the biocompatibility of the hydrogel coating is not ideal.

[0004] To achieve the above purpose, the technical solution adopted by the present invention is:

[0005] In the first aspect, the present invention provides a polymer article with a hydrogel layer coated on its surface, including a polymer substrate and a hydrogel layer coated on the surface of the polymer substrate; the hydrogel layer includes a natural polymer cross-linked network, and the natural polymer cross-linked network is cross-linked by polymerizable natural polymers grafted on the surface of the polymer substrate.

[0006] According to some embodiments of the present invention, the polymerizable natural polymer includes a double-bond modified natural polymer. Generally, a water-soluble double-bond modified natural polymer is selected.

[0007] According to some embodiments of the present invention, the polymerizable natural polymer includes at least one of methacryloyl gelatin and methacryloyl hyaluronic acid.

[0008] According to some embodiments of the present invention, the methacryloyl gelatin has a molecular weight of 30,000 - 90,000 and a substitution degree of 30% - 90%.

[0009] According to some embodiments of the present invention, the methacryloyl hyaluronic acid has a molecular weight of 30,000 - 50,000 and a substitution degree of 25% - 40%.

[0010] Methacryloyl gelatin refers to the product obtained by substituting the amino groups in gelatin with methacryloyl groups, and the substitution degree refers to the percentage of amino groups in gelatin substituted by methacryloyl groups.

[0011] Methacryloyl hyaluronic acid refers to the product obtained by substituting the hydroxyl groups in hyaluronic acid with methacryloyl groups, and the substitution degree refers to the percentage of hydroxyl groups in hyaluronic acid substituted by methacryloyl groups.

[0012] According to some embodiments of the present invention, the polymer substrate has extractable hydrogen atoms.

[0013] According to some embodiments of the present invention, the polymer substrate includes at least one of polyamide, polyester, polyolefin, and polyvinyl chloride.

[0014] According to some embodiments of the present invention, the polymer substrate includes at least one of nylon, polyethylene terephthalate, polyethylene, polypropylene, polyurethane, and polyvinyl chloride.

[0015] According to some embodiments of the present invention, the polymer substrate is of any shape.

[0016] According to some embodiments of the present invention, the thickness of the hydrogel layer is 50 - 250 μm. The hydrogel layer coated on the surface of the polymer product provided by the present invention has a relatively thick thickness, which can not only improve the lubricity of the medical device, but also better achieve drug loading.

[0017] In a second aspect, the present invention provides a method for preparing the polymer product with a hydrogel layer coated on the surface as described in the first aspect, including:

[0018] S1. Swelling the surface of the polymer substrate with a photoinitiator solution and drying;

[0019] S2. Immersing the polymer substrate in a hydrogel precursor solution, where the hydrogel precursor solution contains a polymerizable natural polymer and an optional crosslinking agent;

[0020] S3. The grafting reaction of the photoinitiable natural polymer occurs on the surface of the polymer substrate and the crosslinking reaction occurs between the photoinitiable natural polymers, resulting in a polymer article with a hydrogel layer coated on the surface.

[0021] In the present invention, swelling the surface of the polymer substrate with a photoinitiator solution can be achieved by covering the surface of the polymer substrate with the photoinitiator solution by means of coating, spraying, etc. and keeping it for a period of time, or by immersing the polymer substrate in the photoinitiator solution for a period of time. Before swelling, the polymer substrate can be cleaned with a solvent, treated with plasma, corona or ozone.

[0022] It is relatively easy to prepare a hydrogel layer with a relatively thick thickness on the surface of a flat polymer substrate, and the coating thickness can be controlled by adjusting the coating process to form a relatively thick and uniform hydrogel layer on the surface of the polymer substrate. However, if the shape of the polymer substrate is not regular, especially with relatively fine structures, it is simply impossible to form a hydrogel layer with a relatively thick and uniform thickness on the surface of the polymer substrate by the coating process. The preparation method provided by the present invention can immerse the polymer substrate in the hydrogel precursor solution, so that the photoinitiable natural polymer is grafted onto the surface of the polymer substrate under the action of ultraviolet light and crosslinked, and a hydrogel layer with a relatively thick and uniform thickness and excellent biocompatibility can be prepared on the surface of polymer substrates in various forms.

[0023] In the present invention, the crosslinking reaction between the photoinitiable natural polymers is initiated by the photoinitiator embedded on the surface of the substrate and can also be strengthened by additionally adding a crosslinking agent. Relatively speaking, adding a crosslinking agent to the hydrogel precursor solution is more conducive to preparing a hydrogel layer with a relatively thicker thickness on the surface of the polymer substrate.

[0024] According to some embodiments of the present invention, the ultraviolet light used to initiate the grafting reaction can select various common ultraviolet light sources, such as high-pressure or low-pressure mercury lamps, cold cathode tubes, black lights, ultraviolet light-emitting diodes, ultraviolet lasers and flashlights, and preferably a light source with a main wavelength of 200-400 nm.

[0025] According to some embodiments of the present invention, the photoinitiator is a photoinitiator for Norrish II type reaction.

[0026] According to some embodiments of the present invention, the photoinitiator is selected from at least one of benzophenone, substituted benzophenone, thioxanthone, anthraquinone, benzoylformate, camphorquinone.

[0027] According to some embodiments of the present invention, the photoinitiator is selected from at least one of benzophenone, 4-methylbenzophenone, 3,3'-dimethyl-4-methoxybenzophenone, benzophenone-2-formyl(tetraethoxy)acrylate, benzophenone-2-methyl formate, 2-isopropylthioxanthone, 2-isopropylthioxanthone, 2,4-diethylthioxanthone, and benzil.

[0028] According to some embodiments of the present invention, the solvent of the photoinitiator solution is an organic solvent that can swell the polymer substrate, and is preferably selected from at least one of aliphatic hydrocarbons, aromatic hydrocarbons, halogenated hydrocarbons, ketones, alcohols, and ethers.

[0029] In the present invention, the photoinitiator is a Norrish II type photoinitiator that is soluble in the above solvent.

[0030] According to some embodiments of the present invention, the crosslinking agent contains at least two polymerizable double bonds.

[0031] According to some embodiments of the present invention, the crosslinking agent is selected from at least one of methylene bisacrylamide, polyethylene glycol diacrylate, tripropylene glycol diacrylate, and ethylene glycol dimethacrylate.

[0032] According to some embodiments of the present invention, the swelling treatment time is 2 to 10 min.

[0033] According to some embodiments of the present invention, the reaction time of the grafting reaction is 5 to 30 min.

[0034] According to some embodiments of the present invention, the irradiation intensity of the ultraviolet light is 300 to 800 mW / cm 2 , and the irradiation time is 10 to 40 min.

[0035] According to some embodiments of the present invention, the content of the photoinitiator in the photoinitiator solution is 5 to 20 wt%.

[0036] According to some embodiments of the present invention, the content of the polymerizable natural polymer in the hydrogel precursor solution is 2 to 15 wt%, and the mass of the crosslinking agent is 0 to 5% of the mass of the polymerizable natural polymer.

[0037] In a third aspect, the present invention provides the use of the polymer article with a surface-coated hydrogel layer described in the first aspect or the polymer article with a surface-coated hydrogel layer prepared by the preparation method described in the second aspect in medical devices, especially medical devices with high lubricity.

[0038] The beneficial effects of the present invention are at least as follows:

[0039] The polymer article with a surface-coated hydrogel layer provided by the present invention has a hydrogel layer with uniform thickness and excellent biocompatibility coated on the surface of the polymer substrate, and can be used for preparing medical devices with high requirements for lubrication performance. Detailed implementation manners

[0040] In order to make the technical problems, technical solutions and beneficial effects to be solved by the present invention clearer and more understandable, the present invention will be further described in detail below in conjunction with specific implementation manners. It should be understood that the specific implementation manners described here are only used to explain this patent in detail and do not limit the protection scope of the present invention in any way.

[0041] Unless otherwise defined, the technical terms used in the following examples have the same meanings as commonly understood by those skilled in the art to which the present invention belongs. The reagents used in the following examples are all conventional biochemical reagents unless otherwise specified; the raw materials, instruments and equipment used in the following examples can all be obtained through market purchase or can be obtained by existing methods; the reagent dosages are all the dosages of reagents in conventional experimental operations unless otherwise specified; the experimental methods are all conventional methods unless otherwise specified.

[0042] In the examples and comparative examples of the present invention, all reagents are obtained through commercial channels.

[0043] Example 1

[0044] Take a nylon sheet (2 cm × 8 cm) with a thickness of 2 mm, clean it successively with ethanol and water and dry it with N 2 air flow to obtain a clean substrate surface. Prepare an isopropyl alcohol solution of benzophenone with a concentration of 10 wt%, immerse the nylon sheet in the solution for swelling, take it out after 5 minutes and dry it with N 2 air flow. Add 10 g of methacryloyl gelatin (Xi'an Ruixi Biotechnology Co., Ltd., molecular weight 30,000, substitution degree 90%) and 0.3 g of methylene bisacrylamide to 100 g of deionized water to prepare a hydrogel precursor solution. Immerse the swollen and dried nylon sheet in the hydrogel precursor solution, turn on the ultraviolet light source (wavelength 365 nm), and the ultraviolet irradiation intensity is 300 mW / cm 2 , irradiate for 20 minutes. Take out the nylon sheet from the solution and rinse the surface with deionized water to obtain a nylon sheet with a surface-coated hydrogel layer.

[0045] Example 2

[0046] Take a polyvinyl chloride sheet (2 cm × 8 cm) with a thickness of 2 mm, clean it successively with ethanol and water and dry it with N 2Air drying was performed to obtain a clean substrate surface. A 15 wt% benzophenone acetone solution was prepared, and the polyvinyl chloride sheet was immersed in the solution for swelling. After 5 minutes, the sheet was taken out and washed with N 2 Air flow drying. Add 8g of methacryloyl hyaluronic acid (Xi'an Ruixi Biological, molecular weight 30,000, degree of substitution 30%) and 0.4g of polyethylene glycol diacrylate (molecular weight 10,000) to 100g of deionized water to obtain a hydrogel precursor solution. Immerse the swollen and dried polyvinyl chloride sheet in the hydrogel precursor solution, turn on the ultraviolet light source (wavelength 365nm), and the ultraviolet irradiation intensity is 300mW / cm 2 The polyvinyl chloride sheet was taken out from the solution and the surface was washed with deionized water to obtain a polyvinyl chloride sheet with a hydrogel layer on the surface.

[0047] Example 3

[0048] Take a 2 mm thick polyethylene sheet (2 cm × 8 cm), wash it with ethanol and water, and 2 Air flow drying was performed to obtain a clean substrate surface. A 15 wt% 4-methylbenzophenone toluene solution was prepared, and the polyethylene sheet was immersed in the solution for swelling. After 5 min, the sheet was taken out and washed with N 2 Air drying. Add 6 g of methacryloyl gelatin (Xi'an Qiyue Biotechnology Co., Ltd., molecular weight 60,000, degree of substitution 80%) and 0.24 g of polyethylene glycol diacrylate (molecular weight 4,000) to 100 g of deionized water to obtain a hydrogel precursor solution. Immerse the swollen and dried polyethylene sheet in the hydrogel precursor solution, turn on the ultraviolet light source (wavelength 365 nm), and the ultraviolet irradiation intensity is 300 mW / cm 2 The polyethylene sheet was taken out from the solution and the surface was washed with deionized water to obtain a polyethylene sheet with a hydrogel layer on the surface.

[0049] Example 4

[0050] The preparation method of the nylon sheet with a surface coated with a hydrogel layer is similar to that of Example 1, except that 0.3 g of methylenebisacrylamide is not added when preparing the hydrogel precursor solution.

[0051] Comparative Example 1

[0052] Take a 2 mm thick nylon sheet (2 cm × 8 cm), wash it with ethanol and water, and 2Air drying was performed to obtain a clean substrate surface. 10 g of methacryloyl gelatin (Xi'an Ruixi Biotechnology Co., Ltd., molecular weight 30,000, substitution degree 90%) and 0.3 g of methylenebisacrylamide were added to 100 g of deionized water to prepare a hydrogel precursor solution. The nylon sheet was immersed in the hydrogel precursor solution, and the ultraviolet light source (wavelength 365 nm) was turned on. The ultraviolet irradiation intensity was 300 mW / cm 2 and irradiated for 20 min. The nylon sheet was taken out of the solution and the surface was rinsed with deionized water, and a nylon sheet with a hydrogel layer coated on the surface was not obtained.

[0053] Comparative Example 2

[0054] A nylon sheet with a thickness of 2 mm (2 cm × 8 cm) was taken, and it was successively cleaned with ethanol and water and dried with N 2 Air drying was performed to obtain a clean substrate surface. An isopropanol solution of benzophenone with a concentration of 10 wt% was prepared, and the nylon sheet was immersed in the solution for swelling. After 5 min, it was taken out and dried with N 2 Air drying. 20 g of acrylamide and 0.8 g of methylenebisacrylamide were added to 100 g of deionized water to prepare a hydrogel precursor solution. The swollen and dried nylon sheet was immersed in the hydrogel precursor solution, and the ultraviolet light source (wavelength 365 nm) was turned on. The ultraviolet irradiation intensity was 300 mW / cm 2 and irradiated for 20 min. The nylon sheet was taken out of the solution and the surface was rinsed with deionized water, and a nylon sheet with a hydrogel layer coated on the surface was obtained.

[0055] Comparative Example 3

[0056] A nylon sheet with a thickness of 2 mm (2 cm × 8 cm) was taken, and it was successively cleaned with ethanol and water and dried with N 2 Air drying was performed to obtain a clean substrate surface. An isopropanol solution of benzophenone with a concentration of 10 wt% was prepared, and the nylon sheet was immersed in the solution for swelling. After 5 min, it was taken out and dried with N 2 Air drying. 20 g of acrylamide and 5 g of gelatin were added to 100 g of deionized water to prepare a hydrogel precursor solution. The swollen and dried nylon sheet was immersed in the hydrogel precursor solution, and the ultraviolet light source (wavelength 365 nm) was turned on. The ultraviolet irradiation intensity was 300 mW / cm 2 and irradiated for 20 min. The nylon sheet was taken out of the solution and the surface was rinsed with deionized water, and a nylon sheet with a hydrogel layer coated on the surface was obtained.

[0057] Evaluation of hydrogel layer thickness and roughness

[0058] The thickness and roughness of the hydrogel layer on the surface of the polymer products prepared in each example and comparative example were measured. The measurement method was as follows: The polymer substrate coated with the hydrogel layer on the surface was immersed in an aqueous solution containing a hydrophilic fluorescent reagent for swelling, and its thickness and roughness were tested with a ZEISS laser confocal microscope LSM 900MAT.

[0059] The results are shown in the following table:

[0060] Group Hydrogel layer thickness (μm) Roughness (μm) Example 1 50 0.09 Example 2 81 0.05 Example 3 65 0.07 Example 4 18 0.15 Comparative Example 1 / / Comparative Example 2 38 0.12 Comparative Example 3 47 0.09

[0061] Biocompatibility evaluation of the hydrogel layer

[0062] Mouse fibroblast L929 cells were cultured on the polymer material for 2 days, and the relative growth rate (RGR) of the cells was detected by the Cell Counting Kit-8 (CCK8) method to evaluate the biocompatibility of the hydrogel-modified polymer material. The higher the RGR, the better the cell activity and the lower the cytotoxicity of the tested reagent or material. Conversely, the lower the RGR, the worse the cell activity and the higher the cytotoxicity of the tested reagent or material.

[0063] The results of the relative cell growth rate of the hydrogel layer on the surface of the polymer products prepared in each example and comparative example are shown in the following table:

[0064] Group Relative cell proliferation rate (%) Example 1 98％ Example 2 99％ Example 3 98％ Example 4 97％ Comparative Example 1 / Comparative Example 2 90％ Comparative Example 3 92％

[0065] It can be seen from the above test results that the polymer product with a hydrogel layer coated on the surface provided by the present invention has good lubricity (low roughness) and biocompatibility.

[0066] It should be noted that the above-described embodiments are only used to explain the present invention and do not constitute any limitation to the present invention. The present invention has been described by referring to typical embodiments, but it should be understood that the words used therein are descriptive and explanatory words rather than limiting words. Modifications can be made to the present invention within the scope of the claims of the present invention as provided, and the present invention can be revised without departing from the scope and spirit of the present invention. Although the present invention described therein relates to specific methods, materials, and embodiments, it does not mean that the present invention is limited to the specific examples disclosed therein. On the contrary, the present invention can be extended to all other methods and applications with the same function.

Claims

1. A polymer article with a hydrogel layer coated on its surface, characterized in that, it includes a polymer substrate and a hydrogel layer coated on the surface of the polymer substrate; the hydrogel layer includes a natural polymer cross-linked network, and the natural polymer cross-linked network is cross-linked by polymerizable natural polymers grafted on the surface of the polymer substrate.

2. The polymer article according to claim 1, characterized in that, the polymerizable natural polymer includes a double-bond modified natural polymer; preferably, the polymerizable natural polymer includes at least one of methacryloyl gelatin and methacryloyl hyaluronic acid.

3. The polymer article according to claim 1 or 2, characterized in that, the polymer substrate has extractable hydrogen atoms; preferably, the polymer substrate includes at least one of polyamide, polyester, polyolefin, and polyvinyl chloride; more preferably, the polymer substrate includes at least one of nylon, polyethylene terephthalate, polyethylene, polypropylene, polyurethane, and polyvinyl chloride.

4. The polymer article according to any one of claims 1-3, characterized in that, the thickness of the hydrogel layer is 50-250 μm.

5. A method for preparing the polymer article according to any one of claims 1-4, characterized in that, it includes: S1. Swelling the surface of the polymer substrate with a photoinitiator solution and drying; S2. Immersing the polymer substrate in a hydrogel precursor solution, and the hydrogel precursor solution contains polymerizable natural polymers and an optional cross-linking agent; S3. Using ultraviolet light to initiate the grafting reaction of polymerizable natural polymers on the surface of the polymer substrate and the cross-linking reaction between polymerizable natural polymers to obtain a polymer article with a hydrogel layer coated on its surface.

6. The preparation method according to claim 5, characterized in that, the photoinitiator is a photoinitiator for Norrish II type reaction; preferably, the photoinitiator is selected from at least one of benzophenone, substituted benzophenone, thioxanthone, anthraquinone, benzoylformate, and camphorquinone; more preferably, the photoinitiator is selected from at least one of benzophenone, 4-methylbenzophenone, 3,3'-dimethyl-4-methoxybenzophenone, benzophenone-2-formyl(tetraethoxy)acrylate, benzophenone-2-formate methyl ester, 2-isopropylthioxanthone, 2-isopropylthioxanthone, 2,4-diethylthioxanthone, and benzil.

7. The preparation method according to claim 5 or 6, characterized in that, the solvent of the photoinitiator solution is an organic solvent that can swell the polymer substrate, preferably selected from at least one of aliphatic hydrocarbons, aromatic hydrocarbons, halogenated hydrocarbons, ketones, alcohols, and ethers.

8. The preparation method according to any one of claims 5-7, characterized in that, the cross-linking agent contains at least two polymerizable double bonds; preferably, the cross-linking agent is selected from at least one of methylene bisacrylamide, polyethylene glycol diacrylate, tripropylene glycol diacrylate, and ethylene glycol dimethacrylate.

9. The preparation method according to any one of claims 5-8, characterized in that, the reaction time of the grafting reaction is 5-30 min; And / or, the irradiation intensity of the ultraviolet light is 300-800 mW / cm 2 , and the irradiation time is 10-40 min; And / or, the content of the photoinitiator in the photoinitiator solution is 5-20 wt%; And / or, the content of the polymerizable natural polymer in the hydrogel precursor solution is 2-15 wt%, and the mass of the crosslinking agent is 0-5% of the mass of the polymerizable natural polymer.

10. Use of the polymer article with a surface-coated hydrogel layer according to any one of claims 1-4 or the polymer article with a surface-coated hydrogel layer prepared by the preparation method according to any one of claims 5-9 in a medical device, especially a highly lubricious medical device.