WO2023279663A1 - 用于植入式医疗器械的表面亲水层修饰方法和应用 - Google Patents
用于植入式医疗器械的表面亲水层修饰方法和应用 Download PDFInfo
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- WO2023279663A1 WO2023279663A1 PCT/CN2021/138085 CN2021138085W WO2023279663A1 WO 2023279663 A1 WO2023279663 A1 WO 2023279663A1 CN 2021138085 W CN2021138085 W CN 2021138085W WO 2023279663 A1 WO2023279663 A1 WO 2023279663A1
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- hydrophilic layer
- medical device
- implantable medical
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- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/08—Materials for coatings
- A61L31/082—Inorganic materials
- A61L31/088—Other specific inorganic materials not covered by A61L31/084 or A61L31/086
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/20—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
- A61L2300/30—Compounds of undetermined constitution extracted from natural sources, e.g. Aloe Vera
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2400/00—Materials characterised by their function or physical properties
- A61L2400/18—Modification of implant surfaces in order to improve biocompatibility, cell growth, fixation of biomolecules, e.g. plasma treatment
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2420/00—Materials or methods for coatings medical devices
- A61L2420/02—Methods for coating medical devices
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2420/00—Materials or methods for coatings medical devices
- A61L2420/04—Coatings containing a composite material such as inorganic/organic, i.e. material comprising different phases
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2420/00—Materials or methods for coatings medical devices
- A61L2420/06—Coatings containing a mixture of two or more compounds
Definitions
- the invention belongs to the technical field of medical devices, in particular to a method and application for modifying a surface hydrophilic layer of implantable medical devices.
- Implantable medical devices are in direct contact with tissues and organs in the human body, causing mutual friction, which may cause damage to tissues and organs, make patients feel uncomfortable, and even cause a series of complications in severe cases. Therefore, improve The surface lubricity of implantable medical devices is particularly important. Surface hydrophilic modification is an effective method to improve the lubrication effect of medical devices and reduce the friction between them and tissues and organs, and it is of great significance to promote the application of implantable medical devices.
- the methods for hydrophilic treatment of the surface of medical devices mainly include: 1. By preparing a hydrogel layer on the surface of the medical device, the lubricity and hydrophilicity of the medical device are better improved. The device lacks a strong connection, and it is easy to fall off after multiple frictions, which affects the durable use of the hydrophilic layer (CN112574460A and CN107412883B); 2. By preparing the organic/inorganic hybrid composite hydrophilic layer, the hydrophilic layer is improved to a certain extent Water-based, but the material preparation is carried out in organic solvents, which affects its biological application (CN107158484A).
- the object of the present invention is to provide a surface hydrophilic layer modification method and application for implantable medical devices.
- the invention improves the lubricity of the surface of the medical device by modifying the hydrophilic layer, reduces the resistance of the medical device, reduces the damage to tissues and organs caused by implanting the medical device, reduces complications, and improves its biocompatibility.
- the first aspect of the present invention provides a surface hydrophilic layer modification method for implantable medical devices.
- the surface hydrophilic layer modification method includes plasma hydrophilic modification, hydrogel hydrophilic Modification and biological extract modification.
- Step 1a Select a water-soluble polymer with excellent biocompatibility, add a certain amount of viscous components, mix well, prepare an aqueous solution of a certain concentration, dry it into a film and soak it in a certain concentration of divalent or trivalent metal cations solution, or by changing external conditions to achieve cross-linking to obtain hydrogel;
- Step 1b Mix a water-soluble polymer with excellent biocompatibility, a cross-linking agent, an initiator, and a certain amount of viscous components to prepare an aqueous solution of a certain concentration, and cross-link into a hydrogel by ultraviolet light, heating, and radiation ;
- Step 2 Uniformly coat the hydrogel obtained in step 1a or step 1b on the surface of the medical device to prepare a hydrogel hydrophilic layer.
- the water-soluble polymer with excellent biocompatibility is selected from sodium alginate, chitosan, hyaluronic acid, elastin, polypeptide, gelatin, collagen, peptidoglycan, agar, starch, cellulose , carboxymethyl cellulose, carboxymethyl chitin, polyhydroxyethyl methacrylate, methacrylic anhydride gelatin, polymethacrylic acid, sodium polymethacrylate, polyacrylic acid, sodium polyacrylate, polyacrylamide, Polyethylacrylic acid, polypropylacrylic acid, polyvinylbenzoic acid, polyisopropylacrylamide, polylysine, poly-L-glutamic acid, polyaspartic acid, polyglycine, polyitaconic acid, poly One or more of vinyl alcohol, carboxylated polyvinyl alcohol, polyethylene oxide, polyethylene glycol, polyethylene glycol diacrylate, polyurethane, polyvinylpyrrolidone, polymaleic anhydride
- the viscous component in step 1a and step 1b is selected from any one of polydopamine, viscous protein, and medical glue, and the mass fraction of the viscous component is 0.1%-20%.
- the concentration of the aqueous solution prepared from the water-soluble polymer and the viscous component in step 1a is 0.1mmol/L-10mol/L.
- the divalent or trivalent metal cations are selected from one or more of Ca 2+ , Mg 2+ , Ba 2+ , Fe 2+ , Zn 2+ , Mn 2+ , Fe 3+ , and Al 3+ .
- the total concentration of the divalent or trivalent metal cations is 0.1mmol/L-10mol/L.
- changing the external conditions in step 1a is changing the temperature or adjusting the pH, and selecting the corresponding cross-linking method according to different reaction systems, and the range of changing the temperature is -20°C-100°C.
- the range of adjusting pH is 1-14. It is worth mentioning that the present invention includes a variety of different pH crosslinking systems, including acidic and alkaline systems, so the pH range is wide.
- the crosslinking time is 1min-24h.
- step 1b the mass fraction of the crosslinking agent is 0.1%-20%, the mass fraction of the initiator is 0.1%-20%, and the crosslinking time is 1min-24h.
- hydrophilic modification process of the biological extract lubricating layer is as follows:
- the biological extract containing hydrophilic lubricating substances is prepared into a viscous aqueous solution, and then coated on the surface of the medical device, and the coating is selected from any one of spray coating, dip coating, drop coating, spin coating and bioprinting .
- the biological extract containing hydrophilic lubricating substances is at least one selected from surface mucus of kelp, surface mucus of fish, snail mucus, aloe mucus, and mushroom liquid.
- the hydrophilic lubricating substance contained in the surface mucus of kelp is mainly mannitol
- the hydrophilic lubricating substance contained in the surface mucus of fish is mainly mucopolysaccharide
- the hydrophilic lubricating substance contained in the snail mucus is mainly mannitol.
- the lubricating substances are mainly allantoin, glycolic acid and collagen
- the hydrophilic lubricating substances contained in the aloe mucus are mainly mannan.
- the viscous aqueous solution of the biological hydrophilic lubricating substance is 0.1mmol/L-10mol/L.
- the soaking time is 1-24h.
- the plasma hydrophilic modification is at least one selected from oxygen plasma, ammonia plasma, hydrogen plasma, carbon dioxide plasma and other gas plasmas.
- the vacuum degree is -0.1 ⁇ -0.095
- the voltage is 600-800V
- the plasma surface treatment time is 1-60min.
- the plasma modification process is as follows:
- the medical device is an instrument, equipment, appliance and material directly used in the human body, and is made of gold, silver, platinum, palladium, copper, steel, tantalum, magnesium, nickel, chromium, iron , nickel-titanium alloy, cobalt-chromium alloy, gallium arsenide, titanium, polylactic acid, polyglycolic acid, polylactic acid-glycolic acid copolymer, poly ⁇ -(caprolactone), polyanhydride, polyorthoester, polyvinyl alcohol , polyethylene glycol, polyurethane, polyacrylic acid, poly-N-isopropylacrylamide, poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide), polytetrafluoroethylene, polycarbonate Ester, polyurethane, nitrocellulose, polystyrene, polyethylene, polyethylene terephthalate, polydimethylsiloxane, polyether ether ketone, silicon oxide, titanium oxide,
- contact lenses Includes contact lenses, urinary catheters, intravaginal or gastrointestinal devices (stomach tube, sigmoidoscope, colonoscope, gastroscope), endotracheal tubes, bronchoscopes, dentures, orthodontic appliances, intrauterine devices, burn tissue dressings, or Any of therapeutic instruments, laparoscopes, arthroscopes, dental filling materials, artificial muscle bonds, artificial larynx, and subperiosteal implants.
- the second aspect of the present invention provides the application of the above method for modifying the surface hydrophilic layer of an implantable medical device in biomedicine.
- the third aspect of the present invention provides a surface hydrophilic layer of an implantable medical device, which is characterized in that it is obtained by the above method for modifying the surface hydrophilic layer of an implantable medical device.
- the fourth aspect of the present invention provides an implantable medical device with a hydrophilic layer modification, which is obtained by the above-mentioned method for modifying a surface hydrophilic layer of an implantable medical device.
- the present invention provides a surface hydrophilic layer modification method and application for implantable medical devices, through plasma hydrophilic modification, or biocompatible water-soluble polymers and viscous
- the hydrogel prepared by the ingredients, or the biological extract, modifies the surface of the medical device to form a hydrophilic layer on the surface.
- the present invention has the following advantages:
- the present invention uses plasma, hydrogel, and biological extracts to modify the surface of implantable medical devices to enhance their hydrophilic properties, and it is confirmed by lubricity tests that it significantly improves the lubricity of the surface of medical devices and significantly reduces
- the resistance of medical devices during use reduces the damage to tissues and organs, thereby reducing complications, and the durability test proves that its lubrication effect has excellent durability.
- the surface hydrophilic layer modification method for implantable medical devices provided by the present invention has simple process, convenient operation, safety and environmental protection, and hydrogel modification and biological extract modification can be realized in the water phase , no need to introduce organic solvents, so it has good biocompatibility.
- the hydrogel modification provided by the present invention increases the adhesion between the hydrogel and the surface of the medical device by adding viscous components and making it evenly dispersed in the system, so that it can be tightly combined with the medical device, giving Its a certain persistence.
- the present invention selects biological extracts such as kelp surface mucus, fish surface mucus, and aloe vera mucus to treat the medical device, endows it with excellent biocompatibility, and increases the surface hydrophilic layer and the surface of the medical device. Adhesive force reduces the probability of falling off.
- Hydrophilicity test the water contact angle of the hydrophilic modified laparoscope is 20°, and the water contact angle of the unmodified laparoscope is 108°.
- Lubrication performance and durability test the coefficient of friction can be used as an important index to measure the lubrication performance of the hydrophilic layer.
- the hydrophilic modified laparoscope was fixed in the fixture of the modified stress rheometer, and a clamping force of 4 N was applied to it. Start at a constant speed and test the required pulling force. The ratio of the pulling force to the clamping force is the coefficient of friction.
- the friction coefficient of the hydrophilic modified laparoscope was reduced by 95% compared with the unmodified laparoscope, and the friction coefficient did not change significantly after multiple friction measurements.
- Hydrophilicity test the water contact angle of the hydrophilically modified gastroscope is 24°, and the water contact angle of the unmodified gastroscope is 100°.
- Lubrication performance and durability test the coefficient of friction can be used as an important index to measure the lubrication performance of the hydrophilic layer.
- the hydrophilic modified gastroscope was fixed in the fixture of the modified stress rheometer, and a clamping force of 4 N was applied to it, and the Start, test the required pulling force, the ratio of pulling force and clamping force is the coefficient of friction.
- the friction coefficient of the hydrophilic modified gastroscope was reduced by 96%. After multiple friction measurements, the friction coefficient did not change significantly.
- Hydrophilicity test the water contact angle of the artificial tendon after hydrophilic modification is 15°, and the water contact angle of the unmodified artificial tendon is 104°.
- Lubrication performance and durability test The coefficient of friction can be used as an important index to measure the lubrication performance of the hydrophilic layer.
- the hydrophilic modified artificial tendon was fixed in the fixture of the modified stress rheometer, and a clamping force of 4 N was applied to it. Start at a constant speed and test the required pulling force. The ratio of the pulling force to the clamping force is the coefficient of friction.
- the uniformly dispersed polydopamine can increase the viscosity of sodium alginate hydrogel, and then the hydrogel is taken out from the mold and evenly coated on the surface of the catheter to achieve urinary catheterization. Tubes of Hydrogel Hydrophilic Modification.
- Hydrophilicity test the water contact angle of the hydrophilic modified urinary catheter is 10°, and the water contact angle of the unmodified urinary catheter is 100°.
- Adhesion test fix the urinary catheter coated with the hydrophilic layer on a stretching machine, and test the shear adhesion strength of the hydrophilic layer and the catheter.
- the shear adhesion strength of the hydrophilic layer is 80 kPa, high
- the shear adhesion strength of commercial glue is 40 kPa.
- Lubrication performance and durability test the coefficient of friction can be used as an important index to measure the lubrication performance of the hydrophilic layer.
- the hydrophilic modified catheter was fixed in the fixture of the modified stress rheometer, and a clamping force of 4 N was applied to it , start at a constant speed, test the required pulling force, the ratio of pulling force and clamping force is the coefficient of friction.
- the coefficient of friction of the hydrophilic modified catheter was reduced by 96% compared with that of the unmodified catheter, and there was no significant change in the coefficient of friction after multiple friction measurements.
- the uniformly dispersed polydopamine increases the viscosity of the polyacrylic acid hydrogel, and then the hydrogel is taken out from the mold and evenly coated on the surface of the bronchoscope to realize the hydrogel of the bronchoscope.
- Glue hydrophilic modification
- Hydrophilicity test the water contact angle of the hydrophilic modified bronchoscope is 11°, and the water contact angle of the unmodified bronchoscope is 110°.
- Adhesion test fix the bronchoscope coated with the hydrophilic layer on a stretching machine, and test the shear adhesion strength between the hydrophilic layer and the bronchoscope.
- the shear adhesion strength of the hydrophilic layer is 76 kPa, which is higher than that of commercial products
- the shear adhesion strength of the glue is 40 kPa.
- Lubrication performance and durability test the coefficient of friction can be used as an important index to measure the lubrication performance of the hydrophilic layer.
- the hydrophilic modified bronchoscope was fixed in the fixture of the modified stress rheometer, and a clamping force of 4 N was applied to it. Start at a constant speed and test the required pulling force. The ratio of the pulling force to the clamping force is the coefficient of friction.
- the friction coefficient of the hydrophilic modified bronchoscope was reduced by 95% compared with the unmodified bronchoscope, and the friction coefficient did not change significantly after multiple friction measurements.
- the uniformly dispersed polydopamine increases the viscosity of the polyvinyl alcohol hydrogel, and then the hydrogel is taken out from the mold and evenly coated on the surface of the bronchoscope to realize the hydrogel of the bronchoscope. Hydrophilic modification of the gel.
- Hydrophilicity test the water contact angle of the hydrophilic modified bronchoscope is 9°, and the water contact angle of the unmodified bronchoscope is 102°.
- Adhesion test fix the bronchoscope coated with the hydrophilic layer on a stretching machine, and test the shear adhesion strength between the hydrophilic layer and the bronchoscope.
- the shear adhesion strength of the hydrophilic layer is 70 kPa, which is higher than that of commercial products.
- the shear adhesion strength of the glue is 40 kPa.
- Lubrication performance and durability test the coefficient of friction can be used as an important index to measure the lubrication performance of the hydrophilic layer.
- the hydrophilic modified bronchoscope was fixed in the fixture of the modified stress rheometer, and a clamping force of 4 N was applied to it. Start at a constant speed and test the required pulling force. The ratio of the pulling force to the clamping force is the coefficient of friction.
- the friction coefficient of the hydrophilic modified bronchoscope was reduced by 95% compared with the unmodified bronchoscope, and the friction coefficient did not change significantly after multiple friction measurements.
- the uniformly dispersed polydopamine increases the viscosity of the sodium alginate hydrogel, and then the hydrogel is taken out from the mold and evenly coated on the surface of the colonoscope to realize the hydrogel of the colonoscope. Hydrophilic modification of the gel.
- Hydrophilicity test the water contact angle of the hydrophilically modified colonoscope is 12°, and the water contact angle of the unmodified colonoscope is 90°.
- Adhesion test fix the colonoscope coated with the hydrophilic layer on a stretching machine, and test the shear adhesion strength between the hydrophilic layer and the colonoscope.
- the shear adhesion strength of the hydrophilic layer is 75 kPa, which is higher than that of commercial products
- the shear adhesion strength of the glue is 40 kPa.
- Lubrication performance and durability test the coefficient of friction can be used as an important index to measure the lubrication performance of the hydrophilic layer.
- the hydrophilic modified colonoscope was fixed in the fixture of the modified stress rheometer, and a clamping force of 4 N was applied to it. Start at a constant speed and test the required pulling force. The ratio of the pulling force to the clamping force is the coefficient of friction.
- the coefficient of friction of the hydrophilic modified colonoscope was reduced by 95% compared with that of the unmodified colonoscope, and there was no significant change in the coefficient of friction after multiple friction measurements.
- Mannitol was prepared into a viscous aqueous solution of 2 mol/L, the arthroscope was soaked in the mannitol mucus, soaked for 24 hours, and then taken out to obtain the arthroscope treated with the extract.
- Hydrophilicity test the water contact angle of the hydrophilic modified arthroscope is 9°, and the water contact angle of the unmodified arthroscope is 110°.
- Adhesion test After the mannitol mucus is dry, fix the arthroscope coated with mannitol mucus on a stretching machine, test the shear adhesion strength of the hydrophilic layer and the arthroscope, and the shear strength of the hydrophilic layer.
- the shear adhesion strength is 80 kPa, which is 40 kPa higher than the shear adhesion strength of commercial glue.
- Lubrication performance and durability test the coefficient of friction can be used as an important index to measure the lubrication performance of the hydrophilic layer.
- the hydrophilic modified arthroscope is fixed in the fixture of the modified stress rheometer, and a 4 N clamp is applied to it Force, start at a constant speed, test the required pulling force, the ratio of pulling force and clamping force is the coefficient of friction.
- the coefficient of friction of the hydrophilic modified arthroscope was reduced by 96% compared with the unmodified arthroscope, and there was no significant change in the coefficient of friction after multiple friction measurements.
- the fish used in the present embodiment is grass carp, but the present invention is not limited thereto, it should be pointed out that most of the fish surface has mucus material, is applicable to implementing the present invention equally, therefore all belongs to protection of the present invention scope.
- the mucopolysaccharide was prepared into a viscous aqueous solution of 2 mol/L, the gastroscope was soaked in the mucopolysaccharide mucus, soaked for 24 hours, and then taken out to obtain the gastroscope treated with the extract.
- Hydrophilicity test the water contact angle of the hydrophilically modified gastroscope is 14°, and the water contact angle of the unmodified gastroscope is 105°.
- Adhesion test After the mucopolysaccharide is dried, the gastroscope coated with mucopolysaccharide mucus is fixed on a stretching machine, and the shear adhesion strength between the hydrophilic layer and the gastroscope is tested.
- the shear adhesion strength of the hydrophilic layer is 80 kPa , 40 kPa higher than the shear adhesion strength of commercial glue.
- Lubrication performance and durability test the coefficient of friction can be used as an important index to measure the lubrication performance of the hydrophilic layer.
- the hydrophilic modified gastroscope was fixed in the fixture of the modified stress rheometer, and a clamping force of 4 N was applied to it, and the Start, test the required pulling force, the ratio of pulling force and clamping force is the coefficient of friction.
- the friction coefficient of the hydrophilic modified gastroscope was reduced by 95%. After multiple friction measurements, the friction coefficient did not change significantly.
- the mannan was prepared into a viscous aqueous solution of 2 mol/L, the arthroscope was soaked in the mannan mucus, soaked for 24 hours, and then taken out to obtain the arthroscope treated with the extract.
- Hydrophilicity test the water contact angle of the hydrophilic modified arthroscope is 10°, and the water contact angle of the unmodified arthroscope is 113°.
- Adhesion test After the kelp mucus is dry, fix the arthroscope coated with kelp mucus on a stretching machine, test the shear adhesion strength of the hydrophilic layer and the arthroscope, and the shear adhesion of the hydrophilic layer.
- the adhesion strength is 83 kPa, which is 40 kPa higher than the shear adhesion strength of commercial glue.
- Lubrication performance and durability test the coefficient of friction can be used as an important index to measure the lubrication performance of the hydrophilic layer.
- the hydrophilic modified arthroscope is fixed in the fixture of the modified stress rheometer, and a 4 N clamp is applied to it Force, start at a constant speed, test the required pulling force, the ratio of pulling force and clamping force is the coefficient of friction.
- the coefficient of friction of the hydrophilic modified arthroscope was reduced by 96% compared with the unmodified arthroscope, and there was no significant change in the coefficient of friction after multiple friction measurements.
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Abstract
本发明公开了用于植入式医疗器械的表面亲水层修饰方法和应用，属于医疗器械技术领域，其中表面亲水层修饰方法包括等离子体亲水改性、水凝胶亲水改性及生物提取物改性。本发明通过等离子亲水改性，或生物相容性的水溶性高分子与粘性成分制备的水凝胶，或生物提取物，对医疗器械表面进行改性，使其形成亲水层，能够提高生物医疗器械的表面润滑性，降低医疗器械在使用过程中产生的阻力，降低植入医疗器械对组织造成的损伤，减少并发症，提高其生物相容性，具有方法简单、润滑效果好、操作便利、安全环保等优点。本发明还公开了植入式医疗器械表面亲水层和带有亲水层修饰的植入式医疗器械。
Description
本发明属于医疗器械技术领域，尤其涉及一种用于植入式医疗器械的表面亲水层修饰方法和应用。
植入式医疗器械在人体中与组织和器官直接接触，产生相互摩擦，可能会对组织和器官造成损伤，使患者产生不适感，严重的情况下甚至有可能引发一系列并发症，因此，提高植入式医疗器械的表面润滑性尤为重要。表面亲水改性处理是提高医疗器械润滑效果、降低其与组织和器官摩擦的有效方法，对促进植入式医疗器械的应用有重要意义。
目前，对医疗器械表面亲水处理的方法主要包括：1.通过在医疗器械表面制备水凝胶层，较好地改善了医疗器械的润滑性和亲水性，但是由于水凝胶层与医疗器械缺乏有力的连接，在多次摩擦之后容易脱落，影响了亲水层的持久使用（CN112574460A和CN107412883B）；2.通过制备有机/无机杂化复合物亲水层，在一定程度上提高了亲水性，但是材料制备在有机溶剂中进行，对其生物应用产生影响（CN107158484A）。
总的来说，目前对医疗器械亲水改性处理的方法存在亲水润滑效果不持久、生物相容性不佳以及制备方法复杂等问题。因此，开发制备方法简单、润滑效果持久以及生物相容性良好的新型植入式医疗器械亲水层修饰材料的需求尤为迫切。
为了解决上述背景技术中所提出的技术问题，本发明的目的在于提供用于植入式医疗器械的表面亲水层修饰方法和应用。本发明利用亲水层修饰提高医疗器械表面的润滑性，降低医疗器械的阻力，减少植入医疗器械对组织和器官造成的损伤，减少并发症，提高其生物相容性。
本发明第一方面提供用于植入式医疗器械的表面亲水层修饰方法，在本发明的技术方案中，所述表面亲水层修饰方法包括等离子体亲水改性、水凝胶亲水改性及生物提取物改性。
具体地，所述水凝胶亲水改性的过程如下：
步骤1a：选择具有优异生物相容性的水溶性高分子，加入一定量的粘性组分，混合均匀，配制成一定浓度的水溶液，干燥成膜后浸泡在一定浓度的二价或三价金属阳离子溶液中，或通过改变外界条件实现交联得到水凝胶；
步骤1b：将具有优异生物相容性的水溶性高分子、交联剂、引发剂和一定量的粘性组分混合配制成一定浓度的水溶液，经紫外光照、加热以及辐射交联成水凝胶；
步骤2：将步骤1a或者步骤1b得到的水凝胶均匀包覆在医疗器械表面，制备水凝胶亲水层。
进一步地，所述具有优异生物相容性的水溶性高分子选自海藻酸钠、壳聚糖、透明质酸、弹性蛋白、多肽、明胶、胶原蛋白、肽聚糖、琼脂、淀粉、纤维素、羧甲基纤维素、羧甲基甲壳素、聚甲基丙烯酸羟乙酯、甲基丙烯酸酐化明胶、聚甲基丙烯酸、聚甲基丙烯酸钠、聚丙烯酸、聚丙烯酸钠、聚丙烯酰胺、聚乙基丙烯酸、聚丙基丙烯酸、聚乙烯基苯甲酸、聚异丙基丙烯酰胺、聚赖氨酸、聚L‑谷氨酸、聚天冬氨酸、聚甘氨酸、聚衣康氨酸、聚乙烯醇、羧基化聚乙烯醇、聚氧乙烯、聚乙二醇、聚乙二醇双丙烯酸酯、聚氨酯、聚乙烯吡咯烷酮、聚马来酸酐及其衍生物中的一种或多种。
进一步地，步骤1a与步骤1b中所述粘性成分选自聚多巴胺、粘性蛋白、医用胶水中的任意一种，所述粘性组分的质量分数为0.1%-20%。
进一步地，步骤1a中所述水溶性高分子与粘性组分配制成的水溶液浓度所为0 .1mmol/L‑10mol/L。所述二价或三价金属阳离子选自Ca
2+、Mg
2+、Ba
2+、Fe
2+、Zn
2+、Mn
2+、Fe
3+、Al
3+中的一种或几种。所述二价或三价金属阳离子的总浓度为0 .1mmol/L‑10mol/L。
进一步地，步骤1a中所述改变外界条件为改变温度或调节pH，根据不同的反应体系选择相应的交联方法，所述改变温度的范围是-20℃-100℃。所述调节pH的范围是1-14。值得一提的是，本发明包含多种pH交联的不同的体系，有酸性也有碱性体系，因此pH的范围较广。所述交联时间为1min-24h。
进一步地，步骤1b中所述交联剂质量分数为0.1%-20%，所述引发剂质量分数为0.1%-20%，所述交联时间为1min-24h。
具体地，所述生物提取物润滑层的亲水改性过程如下：
将含有亲水性润滑物质的生物提取物，制备成粘稠水溶液，然后涂覆在医疗器械表面，所述涂敷选自喷涂、浸涂、滴涂、旋涂和生物打印中的任一种。
所述含有亲水性润滑物质的生物提取物选自海带的表面粘液、鱼的表面粘液、蜗牛粘液、芦荟粘液、蘑菇液中的至少一种。
在本发明的技术方案中，海带的表面粘液中含有的亲水性润滑物质主要为甘露醇，鱼的表面粘液中含有的亲水性润滑物质主要为粘多糖，蜗牛粘液中含有的亲水性润滑物质主要为尿囊素、甘醇酸和骨胶原，芦荟粘液中含有的亲水性润滑物质主要为甘露聚糖。
进一步地，所述生物亲水性润滑物质的粘稠水溶液为0 .1mmol/L‑10mol/L。
进一步地，所述浸泡时间为1-24h。
具体地，所述等离子体亲水改性选自氧气等离子体、氨气等离子体、氢气等离子体、二氧化碳等离子体以及其它气体等离子体中的至少一种。
进一步地，所述真空度为-0.1~-0.095，所述电压为600-800V，所述等离子体表面处理时间为1-60min。
所述等离子改性过程如下：
用乙醇和水擦拭医疗器械的表面，氮气吹干后，将医疗器械放置于等离子体表面处理仪中，抽真空，调节电压和时间，经过等离子体表面处理使医疗器械表面产生亲水性基团。
进一步地，所述亲水性基团选自C=O羰基、-COOH羧基、−OH羟基等亲水基团中的一种或多种。
在本发明的技术方案中，所述医疗器械为直接用于人体的仪器、设备、器具及材料，由选自金、银、铂、钯、铜、钢、钽、镁、镍、铬、铁、镍钛合金、钴铬合金、砷化镓、钛、聚乳酸、聚乙醇酸、聚乳酸-羟基乙酸共聚物、聚ε-(己内酯)、聚酸酐、聚原酸酯、聚乙烯醇、聚乙二醇、聚氨酯、聚丙烯酸、聚N-异丙基丙烯酰胺、聚(环氧乙烷)-聚(环氧丙烷)-聚(环氧乙烷)、聚四氟乙烯、聚碳酸酯、聚氨酯、硝化纤维、聚苯乙烯、聚乙烯、聚对苯二甲酸乙二醇酯、聚二甲基硅氧烷、聚醚醚酮、氧化硅、氧化钛、氧化铝、氧化铌、有机硅、硅橡胶以及玻璃中的至少一种材料制备而成。包括接触镜、导尿管、阴道内或消化道器械(胃管、乙状结肠镜、结肠镜、胃镜)、气管内管、支气管镜、义齿、畸齿矫正器、宫内避孕器、烧伤组织敷料或治疗器械、腹腔镜、关节内窥镜、齿科充填材料、人工肌键、人工喉以及骨膜下植入物中的任意一种。
本发明第二方面提供上述用于植入式医疗器械的表面亲水层修饰方法在生物医学中的应用。
本发明第三方面提供一种植入式医疗器械表面亲水层，其特征在于，由上述用于植入式医疗器械的表面亲水层修饰方法获得。
本发明第四方面提供一种带有亲水层修饰的植入式医疗器械，其特征在于，由上述用于植入式医疗器械的表面亲水层修饰方法获得。
上述技术方案具有如下优点或者有益效果：本发明提供了用于植入式医疗器械的表面亲水层修饰方法和应用，通过等离子亲水改性，或生物相容性的水溶性高分子与粘性成分制备的水凝胶，或生物提取物，对医疗器械表面进行改性，使其表面形成亲水层，本发明具备以下优点：
（1）本发明利用等离子、水凝胶、生物提取物对植入式医疗器械表面进行改性，增强其亲水性能，并且通过润滑性测试证实其显著提高医疗器械表面的润滑性，显著降低使用过程中医疗器械的阻力，减少其对组织和器官造成的损伤，从而减少并发症，通过持久性测试证明其润滑效果具有优异的持久性。
（2）本发明提供的用于植入式医疗器械的表面亲水层修饰方法，过程简单、操作便利，安全环保，且水凝胶改性与生物提取物改性在水相中即可实现，无需引入有机溶剂，因此具有良好的生物相容性。
（3）本发明提供的水凝胶改性通过添加粘性组分，并使其均匀分散在体系中，增加了水凝胶与医疗器械表面的粘着力，使其与医疗器械能够紧密结合，赋予其一定的持久性。
（4）本发明选用海带的表面粘液、鱼的表面粘液和芦荟粘液等生物提取物对医疗器械进行处理，赋予其优异的生物相容性的同时，增加了表面亲水层与医疗器械表面的粘着力，减小了脱落的概率。
下述实施例仅仅是本发明的一部分实施例，而不是全部的实施例。因此，以下提供的本发明实施例中的详细描述并非旨在限制要求保护的本发明的范围，而是仅仅表示本发明的选定实施例。基于本发明的实施例，本领域技术人员在没有作出创造性劳动的前提下所获得的所有其他实施例，都属于本发明的保护范围。
实施例1
用乙醇和水擦拭腹腔镜的表面，氮气吹干后，将其放置于氧气等离子体表面处理仪中，抽真空，使真空度降为-0.1，调节电压为700V，经过等离子体表面处理2min，使腹腔镜表面产生亲水性基团，实现氧气等离子体的表面亲水改性。
亲水性测试：亲水修饰后的腹腔镜的水的接触角为20°，未经修饰的腹腔镜的水的接触角为108°。
润滑性能及持久性测试：摩擦系数可以作为衡量亲水层润滑性能的重要指标，将亲水修饰的腹腔镜固定在改装的应力流变仪的夹具中，对其施加4 N的夹持力，匀速启动，测试其所需的拉力，拉力和夹持力的比值即为摩擦系数。
亲水修饰后的腹腔镜的摩擦系数相较于未修饰的腹腔镜降低了95%，多次摩擦测量后，摩擦系数没有明显变化。
实施例2
用乙醇和水擦拭胃镜的表面，氮气吹干后，将其放置于氧气等离子体表面处理仪中，抽真空，使真空度降为-0.1，调节电压为700V，经过等离子体表面处理2min，使胃镜表面产生亲水性基团，实现氧气等离子体的表面亲水改性。
亲水性测试：亲水修饰后的胃镜的水的接触角为24°，未经修饰的胃镜的水的接触角为100°。
润滑性能及持久性测试：摩擦系数可以作为衡量亲水层润滑性能的重要指标，将亲水修饰的胃镜固定在改装的应力流变仪的夹具中，对其施加4 N的夹持力，匀速启动，测试其所需的拉力，拉力和夹持力的比值即为摩擦系数。
亲水修饰后的胃镜的摩擦系数相较于未修饰的胃镜降低了96%，多次摩擦测量后，摩擦系数没有明显变化。
实施例3
用乙醇和水擦拭人工肌腱的表面，氮气吹干后，将其放置于氧气等离子体表面处理仪中，抽真空，使真空度降为-0.1，调节电压为700V，经过等离子体表面处理2min，使人工肌腱表面产生亲水性基团，实现氧气等离子体的表面亲水改性。
亲水性测试：亲水修饰后的人工肌腱的水的接触角为15°，未经修饰的人工肌腱的水的接触角为104°。
润滑性能及持久性测试：摩擦系数可以作为衡量亲水层润滑性能的重要指标，将亲水修饰的人工肌腱固定在改装的应力流变仪的夹具中，对其施加4 N的夹持力，匀速启动，测试其所需的拉力，拉力和夹持力的比值即为摩擦系数。
亲水修饰后的人工肌腱的摩擦系数相较于未修饰的人工肌腱降低了97%，多次摩擦测量后，摩擦系数没有明显变化。
实施例4
配制质量分数为5％的海藻酸钠水溶液和质量分数为4%的多巴胺溶液，混合均匀，取5mL混合溶液均匀滴加到3
cm×1cm×200 μm的模具中，25℃下静置5h，形成均匀的膜层。随后，将膜层浸泡在0.1mol/L氯化钙溶液中完全交联24h，形成海藻酸钠水凝胶。该体系中，多巴胺氧化聚合形成聚多巴胺后，均匀分散的聚多巴胺可以增加海藻酸钠水凝胶的粘性，接着将水凝胶从模具中取出，均匀包覆在导尿管表面，实现导尿管的水凝胶亲水修饰。
亲水性测试：亲水修饰后的导尿管的水的接触角为10°，未经修饰的导尿管的水的接触角为100°。
粘附力测试：将包覆亲水层的导尿管固定在拉伸机上，测试亲水层与导尿管的剪切粘附强度，亲水层的剪切粘附强度为80 kPa，高于商品化胶水的剪切粘附强度40 kPa 。
润滑性能及持久性测试：摩擦系数可以作为衡量亲水层润滑性能的重要指标，将亲水修饰的导尿管固定在改装的应力流变仪的夹具中，对其施加4 N的夹持力，匀速启动，测试其所需的拉力，拉力和夹持力的比值即为摩擦系数。
亲水修饰后的导尿管的摩擦系数相较于未修饰的导尿管降低了96%，多次摩擦测量后，摩擦系数没有明显变化。
实施例5
配制质量分数为5％的聚丙烯酸水溶液和质量分数为4%的多巴胺溶液，混合均匀，取5mL混合溶液均匀滴加到3
cm×1cm×200 μm的模具中，25℃下静置5h，形成均匀的膜层。随后，将膜层在pH=7.2下制备聚丙烯酸水凝胶。该体系中，多巴胺氧化聚合形成聚多巴胺后，均匀分散的聚多巴胺增加聚丙烯酸水凝胶的粘性，接着将水凝胶从模具中取出，均匀包覆在支气管镜表面，实现支气管镜的水凝胶亲水修饰。
亲水性测试：亲水修饰后的支气管镜的水的接触角为11°，未经修饰的支气管镜的水的接触角为110°。
粘附力测试：将包覆亲水层的支气管镜固定在拉伸机上，测试亲水层与支气管镜的剪切粘附强度，亲水层的剪切粘附强度为76 kPa，高于商品化胶水的剪切粘附强度40 kPa 。
润滑性能及持久性测试：摩擦系数可以作为衡量亲水层润滑性能的重要指标，将亲水修饰的支气管镜固定在改装的应力流变仪的夹具中，对其施加4 N的夹持力，匀速启动，测试其所需的拉力，拉力和夹持力的比值即为摩擦系数。
亲水修饰后的支气管镜的摩擦系数相较于未修饰的支气管镜降低了95%，多次摩擦测量后，摩擦系数没有明显变化。
实施例6
配制质量分数为5％的聚乙烯醇水溶液和质量分数为4%的多巴胺溶液，混合均匀，取5mL混合溶液均匀滴加到3
cm×1cm×200 μm的模具中，25℃下静置5h，形成均匀的膜层。随后，将膜层在-4℃-60℃之间多次冻融，形成聚乙烯醇水凝胶。该体系中，多巴胺氧化聚合形成聚多巴胺后，均匀分散的聚多巴胺增加聚乙烯醇水凝胶的粘性，接着将水凝胶从模具中取出，均匀包覆在支气管镜表面，实现支气管镜的水凝胶亲水修饰。
亲水性测试：亲水修饰后的支气管镜的水的接触角为9°，未经修饰的支气管镜的水的接触角为102°。
粘附力测试：将包覆亲水层的支气管镜固定在拉伸机上，测试亲水层与支气管镜的剪切粘附强度，亲水层的剪切粘附强度为70 kPa，高于商品化胶水的剪切粘附强度40 kPa 。
润滑性能及持久性测试：摩擦系数可以作为衡量亲水层润滑性能的重要指标，将亲水修饰的支气管镜固定在改装的应力流变仪的夹具中，对其施加4 N的夹持力，匀速启动，测试其所需的拉力，拉力和夹持力的比值即为摩擦系数。
亲水修饰后的支气管镜的摩擦系数相较于未修饰的支气管镜降低了95%，多次摩擦测量后，摩擦系数没有明显变化。
实施例7
配制质量分数为5％的甲基丙烯酸羟乙酯水溶液、4%的聚乙二醇双丙烯酸酯、50μL的2,2-二乙氧基苯乙酮混合溶液以及质量分数为4%的多巴胺溶液，混合均匀，取5mL混合溶液均匀滴加到3
cm×1cm的模具中，在紫外光照下交联10min，形成甲基丙烯酸羟乙酯水凝胶。该体系中，多巴胺氧化聚合形成聚多巴胺后，均匀分散的聚多巴胺增加海藻酸钠水凝胶的粘性，接着将水凝胶从模具中取出，均匀包覆在结肠镜表面，实现结肠镜的水凝胶亲水修饰。
亲水性测试：亲水修饰后的结肠镜的水的接触角为12°，未经修饰的结肠镜的水的接触角为90°。
粘附力测试：将包覆亲水层的结肠镜固定在拉伸机上，测试亲水层与结肠镜的剪切粘附强度，亲水层的剪切粘附强度为75 kPa，高于商品化胶水的剪切粘附强度40 kPa 。
润滑性能及持久性测试：摩擦系数可以作为衡量亲水层润滑性能的重要指标，将亲水修饰的结肠镜固定在改装的应力流变仪的夹具中，对其施加4 N的夹持力，匀速启动，测试其所需的拉力，拉力和夹持力的比值即为摩擦系数。
亲水修饰后的结肠镜的摩擦系数相较于未修饰的结肠镜降低了95%，多次摩擦测量后，摩擦系数没有明显变化。
实施例8
将甘露醇制备成2mol/L的粘稠水溶液，将关节内窥镜浸泡在甘露醇粘液中，浸泡24h后取出，得到提取液处理后的关节内窥镜。
亲水性测试：亲水修饰后的关节内窥镜的水的接触角为9°，未经修饰的关节内窥镜的水的接触角为110°。
粘附力测试：待甘露醇粘液干燥后，将包覆甘露醇粘液的关节内窥镜固定在拉伸机上，测试亲水层与关节内窥镜的剪切粘附强度，亲水层的剪切粘附强度为80 kPa，高于商品化胶水的剪切粘附强度40 kPa 。
润滑性能及持久性测试：摩擦系数可以作为衡量亲水层润滑性能的重要指标，将亲水修饰的关节内窥镜固定在改装的应力流变仪的夹具中，对其施加4 N的夹持力，匀速启动，测试其所需的拉力，拉力和夹持力的比值即为摩擦系数。
亲水修饰后的关节内窥镜的摩擦系数相较于未修饰的关节内窥镜降低了96%，多次摩擦测量后，摩擦系数没有明显变化。
实施例9
本实施例中所使用的鱼类为草鱼，但本发明并非局限于此，应当指出的是，大部分的鱼类表面都有粘液物质，同样适用于实施本发明，因此都属于本发明的保护范围。
将粘多糖制备成2mol/L的粘稠水溶液，将胃镜浸泡在粘多糖粘液中，浸泡24h后取出，得到提取液处理后的胃镜。
亲水性测试：亲水修饰后的胃镜的水的接触角为14°，未经修饰的胃镜的水的接触角为105°。
粘附力测试：待粘多糖干燥后，将包覆粘多糖粘液的胃镜固定在拉伸机上，测试亲水层与胃镜的剪切粘附强度，亲水层的剪切粘附强度为80 kPa，高于商品化胶水的剪切粘附强度40 kPa 。
润滑性能及持久性测试：摩擦系数可以作为衡量亲水层润滑性能的重要指标，将亲水修饰的胃镜固定在改装的应力流变仪的夹具中，对其施加4 N的夹持力，匀速启动，测试其所需的拉力，拉力和夹持力的比值即为摩擦系数。
亲水修饰后的胃镜的摩擦系数相较于未修饰的胃镜降低了95%，多次摩擦测量后，摩擦系数没有明显变化。
实施例10
将甘露聚糖制备成2mol/L的粘稠水溶液，将关节内窥镜浸泡在甘露聚糖粘液中，浸泡24h后取出，得到提取液处理后的关节内窥镜。
亲水性测试：亲水修饰后的关节内窥镜的水的接触角为10°，未经修饰的关节内窥镜的水的接触角为113°。
粘附力测试：待海带粘液干燥后，将包覆海带粘液的关节内窥镜固定在拉伸机上，测试亲水层与关节内窥镜的剪切粘附强度，亲水层的剪切粘附强度为83 kPa，高于商品化胶水的剪切粘附强度40 kPa 。
润滑性能及持久性测试：摩擦系数可以作为衡量亲水层润滑性能的重要指标，将亲水修饰的关节内窥镜固定在改装的应力流变仪的夹具中，对其施加4 N的夹持力，匀速启动，测试其所需的拉力，拉力和夹持力的比值即为摩擦系数。
亲水修饰后的关节内窥镜的摩擦系数相较于未修饰的关节内窥镜降低了96%，多次摩擦测量后，摩擦系数没有明显变化。
以上所述仅为本发明的优选实施例，并非因此限制本发明的专利范围，凡是利用本发明说明书及附图内容所作的等效变换，或直接或间接运用在其他相关的技术领域，均同理包括在本发明的专利保护范围内。
Claims (14)
- 用于植入式医疗器械的表面亲水层修饰方法，其特征在于，所述表面亲水层修饰方法包括等离子体亲水改性、水凝胶亲水改性及生物提取物改性。
- 根据权利要求1所述的用于植入式医疗器械的表面亲水层修饰方法，其特征在于，所述水凝胶亲水改性的过程如下：步骤1a：将具有生物相容性的水溶性高分子与一定量的粘性组分混合均匀，配制成一定浓度的水溶液，干燥成膜后浸泡在二价或三价金属阳离子溶液中交联得到水凝胶，或通过改变外界条件实现交联得到水凝胶；步骤1b：将具有生物相容性的水溶性高分子、交联剂、引发剂和一定量的粘性组分粘性成分混合配制成一定浓度的水溶液，经紫外光照、加热或辐射交联成水凝胶；步骤2：将步骤1a或者步骤1b得到的水凝胶均匀包覆在医疗器械表面。
- 根据权利要求2所述的用于植入式医疗器械的表面亲水层修饰方法，其特征在于，步骤1a与步骤1b中所述具有生物相容性的水溶性高分子选自海藻酸钠、壳聚糖、透明质酸、弹性蛋白、多肽、明胶、胶原蛋白、肽聚糖、琼脂、淀粉、纤维素、羧甲基纤维素、羧甲基甲壳素、聚甲基丙烯酸羟乙酯、甲基丙烯酸酐化明胶、聚甲基丙烯酸、聚甲基丙烯酸钠、聚丙烯酸、聚丙烯酸钠、聚丙烯酰胺、聚乙基丙烯酸、聚丙基丙烯酸、聚乙烯基苯甲酸、聚异丙基丙烯酰胺、聚赖氨酸、聚L‑谷氨酸、聚天冬氨酸、聚甘氨酸、聚衣康氨酸、聚乙烯醇、羧基化聚乙烯醇、聚氧乙烯、聚乙二醇、聚乙二醇双丙烯酸酯、聚氨酯、聚乙烯吡咯烷酮、聚马来酸酐及其衍生物中的一种或多种。
- 根据权利要求2所述的用于植入式医疗器械的表面亲水层修饰方法，其特征在于，步骤1a与步骤1b中所述粘性成分选自聚多巴胺、粘性蛋白、医用胶水中的任意一种，所述粘性组分的质量分数为0.1%-20%。
- 根据权利要求2所述的用于植入式医疗器械的表面亲水层修饰方法，其特征在于，步骤1a中所述水溶性高分子与粘性组分配制成的水溶液浓度为0.1mmol/L‑10mol/L；所述二价或三价金属阳离子选自Ca 2+、Mg 2+、Ba 2+、Fe 2+、Zn 2+、Mn 2+、Fe 3+、Al 3+等的一种或多种；所述二价或三价金属阳离子的总浓度为0 .1mmol/L‑10mol/L；步骤1b中，所述水溶性高分子、交联剂、引发剂和粘性组分配制成的水溶液浓度为0.1mmol/L‑10mol/L。
- 根据权利要求2所述的用于植入式医疗器械的表面亲水层修饰方法，其特征在于，步骤1a中所述改变外界条件为改变温度或调节pH，所述温度范围为-20℃~-100℃，所述调节pH的范围是1-14，所述交联时间为1min-24h。
- 根据权利要求2所述的用于植入式医疗器械的表面亲水层修饰方法，其特征在于，步骤1b中所述交联剂质量分数为0.1%-20%，所述引发剂质量分数为0.1%-20%，所述交联时间为1min-24h。
- 根据权利要求1所述的用于植入式医疗器械的表面亲水层修饰方法，其特征在于，所述生物提取物改性过程如下：将含有亲水性润滑物质的生物提取物制备成粘稠的水溶液，然后涂覆在医疗器械表面，所述涂敷选自喷涂、浸涂、滴涂、旋涂和生物打印中的任一种；所述含有亲水性润滑物质的生物提取物选自海带的表面粘液、鱼的表面粘液、蜗牛粘液、芦荟粘液、蘑菇液中的至少一种。
- 根据权利要求8所述的用于植入式医疗器械的表面亲水层修饰方法，其特征在于，所述生物亲水性润滑物质的粘稠水溶液浓度为0.1mmol/L‑10mol/L，所述浸泡时间为1-24h。
- 根据权利要求1所述的用于植入式医疗器械的表面亲水层修饰方法，其特征在于，所述等离子体亲水改性的真空度为-0.1~-0.095，电压为600-800V，处理时间为1-60min。
- 根据权利要求1-10任一所述的用于植入式医疗器械的表面亲水层修饰方法，其特征在于，所述医疗器械由选自金、银、铂、钯、铜、钢、钽、镁、镍、铬、铁、镍钛合金、钴铬合金、砷化镓、钛、聚乳酸、聚乙醇酸、聚乳酸-羟基乙酸共聚物、聚ε-(己内酯)、聚酸酐、聚原酸酯、聚乙烯醇、聚乙二醇、聚氨酯、聚丙烯酸、聚N-异丙基丙烯酰胺、聚(环氧乙烷)-聚(环氧丙烷)-聚(环氧乙烷)、聚四氟乙烯、聚碳酸酯、聚氨酯、硝化纤维、聚苯乙烯、聚乙烯、聚对苯二甲酸乙二醇酯、聚二甲基硅氧烷、聚醚醚酮、氧化硅、氧化钛、氧化铝、氧化铌、有机硅、硅橡胶以及玻璃中的至少一种材料制备而成。
- 根据权利要求1-10任一所述的用于植入式医疗器械的表面亲水层修饰方法在生物医学中的应用。
- 一种植入式医疗器械表面亲水层，其特征在于，由权利要求1-10任一所述的用于植入式医疗器械的表面亲水层修饰方法获得。
- 一种带有亲水层修饰的植入式医疗器械，其特征在于，由权利要求1-10任一所述的用于植入式医疗器械的表面亲水层修饰方法获得。
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