WO2014044074A1 - 智能可控释放抗菌成分的牙种植体及制备方法 - Google Patents

智能可控释放抗菌成分的牙种植体及制备方法 Download PDF

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Publication number
WO2014044074A1
WO2014044074A1 PCT/CN2013/079105 CN2013079105W WO2014044074A1 WO 2014044074 A1 WO2014044074 A1 WO 2014044074A1 CN 2013079105 W CN2013079105 W CN 2013079105W WO 2014044074 A1 WO2014044074 A1 WO 2014044074A1
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dental implant
implant
film
immersed
ethanol
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PCT/CN2013/079105
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English (en)
French (fr)
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张利
胡盼
李玉宝
周名兵
胡静
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四川大学
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Publication of WO2014044074A1 publication Critical patent/WO2014044074A1/zh

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61C—DENTISTRY; APPARATUS OR METHODS FOR ORAL OR DENTAL HYGIENE
    • A61C8/00—Means to be fixed to the jaw-bone for consolidating natural teeth or for fixing dental prostheses thereon; Dental implants; Implanting tools
    • A61C8/0012—Means to be fixed to the jaw-bone for consolidating natural teeth or for fixing dental prostheses thereon; Dental implants; Implanting tools characterised by the material or composition, e.g. ceramics, surface layer, metal alloy
    • A61C8/0013—Means to be fixed to the jaw-bone for consolidating natural teeth or for fixing dental prostheses thereon; Dental implants; Implanting tools characterised by the material or composition, e.g. ceramics, surface layer, metal alloy with a surface layer, coating
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61C—DENTISTRY; APPARATUS OR METHODS FOR ORAL OR DENTAL HYGIENE
    • A61C19/00—Dental auxiliary appliances
    • A61C19/06—Implements for therapeutic treatment
    • 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
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/28—Materials for coating prostheses
    • A61L27/34—Macromolecular materials
    • 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
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • 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
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/54—Biologically active materials, e.g. therapeutic substances
    • 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
    • A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
    • A61L2300/404—Biocides, antimicrobial agents, antiseptic agents
    • 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
    • A61L2430/00—Materials or treatment for tissue regeneration
    • A61L2430/12—Materials or treatment for tissue regeneration for dental implants or prostheses

Definitions

  • the invention relates to a dental implant with an intelligent and controllable release antibacterial ingredient and a preparation method thereof.
  • dental implants that currently have antibacterial properties.
  • One is to combine the antibacterial agent in the coating on the surface of the implant and optimize the coating structure and the loading and release rate of the antibacterial agent to enable it to have longer antibacterial properties. Since the antibacterial property of the implant is mainly caused by the degradation of the coating, the antibacterial agent is continuously and slowly released. Therefore, due to the slow degradation of the coating at the initial stage of planting, the antibacterial property is weak or even has no effective antibacterial property.
  • Another type of dental implant with antibacterial properties such as Lingzhou Zhao, (Antibacterial nano-stmctured titania coating incorporated with silver nanoparticles Biomaterials.
  • the surface of the implant forms a nanotube array structure having a certain pore diameter, and then an antibacterial component or a drug such as an elemental silver or a silver compound is loaded into the nanotube, so that the antibacterial component is gradually released to achieve the antibacterial purpose.
  • an antibacterial component or a drug such as an elemental silver or a silver compound
  • the antibacterial component is released in a large amount at the initial stage of planting, and the antibacterial property of the implant is maintained for a short time.
  • the present invention firstly provides a dental implant capable of automatically controlling or releasing the antibacterial component according to changes in the environment around the implant, and satisfactorily solves the above-mentioned problems. Based on this, the present invention also provides a method for preparing the dental implant of the intelligent controllable release antibacterial ingredient.
  • the dental implant of the intelligent controllable release antibacterial component is based on the presently reported formation of a nanotubular structural layer on the surface of the dental implant and supporting an antibacterial component (preferably a simple silver or silver compound).
  • the nano-tubular structure layer on the surface of the implant is coated with a ⁇ response sensitive film formed by grafting an organic monomer component on the surface of the polyoxyethylene film or the polyethylene glycol film.
  • the organic monomer component is acrylic acid, ammonium acrylate or methacrylic acid. Acid monomer.
  • the pH-responsive sensitive membrane coated on the surface of the dental implant with the antibacterial component coated with the nano-tubular structure can change the filtration performance of the membrane pores as the pH of the surrounding environment changes.
  • SP Membrane filtration
  • the flux can be increased with the decrease of the pH value of the environment, so that the release amount of the antibacterial component in the nanotubular structure of the implant surface can be adjusted according to the change of the pH value, and the release amount of the antibacterial component can be adjusted according to the pH of the surrounding environment.
  • the “switch" effect of the automatic adjustment of the change When the implant is not inflammatory, the pH of the surrounding environment is normal neutral, the pH response of the sensitive membrane is low, and the release channel is in the corresponding “closed” “State, slow release of the antibacterial component loaded in the nanotubular structure layer on the implant surface; when the acidity of the surrounding environment is increased to pH ⁇ 7 due to inflammation around the implant, the pH response of the sensitive membrane is filtered. When the rate is increased, the release channel is in an "open” state, so that the release amount of the antibacterial component loaded in the nanotubular structure layer on the implant surface is increased, thereby A bactericidal effect.
  • the thickness of the pH-responsive sensitive film in the above structure is too thick or too thin, which has a certain influence on the release of the antibacterial component in the nanotube of the dental implant surface.
  • the thickness of the membrane is too large, although the pH of the environment around the implant can cause the release channel of the antibacterial component to be in an "open" state, but it will have a certain adverse effect on the release of the antibacterial component, and when the thickness is too large, It is easy to affect the coating strength of the film on the surface of the dental implant and is easy to fall off; if the thickness of the film is too small, when the film is unevenly coated on the surface of the dental implant, the thickness of the film is too small or even no film, which is effective It is difficult to fully and effectively exert the effect of regulating the release of antibacterial components, and it is easy to lose the antibacterial components. Therefore, the pH of the above-mentioned dental implant of the present invention is preferably 0.1 to 1.0 mm.
  • the nanotubular structure in the surface nanotubular structure layer of the dental implant of the present invention preferably has a pore diameter of 80 to 100 nm and a pore length of 0.1 to 0.5 ⁇ m.
  • a typical preparation method and process for the dental implant of the above intelligently controlled release antibacterial ingredient of the present invention can be carried out as follows:
  • the surface layer is formed with a nano-tubular structure and loaded with an antibacterial component rear dental implant substrate, which is sequentially impregnated with hydrogen peroxide and a silane coupling agent KH550 in an amount of 5 to 25 wt%, preferably 10 to 20 wt%.
  • the surface is sufficiently coated with an initiator and a coupling agent. There is not much demand for the impregnation process, and it can be carried out at room temperature.
  • the experimental reality is generally immersed in hydrogen peroxide for 5-30 min, preferably 10-20 min; in the silane coupling agent solution, it can be generally immersed for 1-5 min, preferably 2-4 min.
  • the structure in which the antibacterial component is loaded may be operated in a manner which has been reported and/or used, including the aforementioned documents, wherein the antibacterial component is preferably a compound of elemental silver or silver.
  • the molecular weight of the polyoxyethylene is from 100,000 to 7,000,000, and the molecular weight of the polyethylene glycol is in the range of 2,000 to 20,000.
  • the implant substrate after the previous treatment is immersed in an initiator solution and subjected to light treatment, and then washed with at least one of ethanol or acetone and then dried.
  • the initiator solution is an ethanol solution having a benzophenone content of 0.1-2.0 M, preferably 0.1-1.0 M; and the anaerobic condition can be carried out by conventionally introducing an inert gas such as nitrogen to avoid air.
  • the oxygen in the reaction adversely affects the polymerization caused by the radical photoinitiator system.
  • the substrate of the implant treated in the previous step is immersed in an aqueous solution of an organic monomer component having a content of 1.0 to 6.0 M, preferably 1.0 5.0 M, and the grafting reaction on the surface of the film is carried out in an anaerobic environment and under light. After the rate reaches 1% to 25% of the mass of the membrane (the reaction time is usually 0.5-5 hours), it is dried after washing to obtain the dental implant, and the organic monomer component is acrylic acid, ammonium acrylate or methyl group. Monomer of acrylic acid.
  • the method of grafting the surface of the above film can be carried out in the manner of the contents of the publication No. CN102250371A.
  • the treatment time of the initiator solution immersion in the above step 2' is generally 0.5 to 3 hours, preferably 0.5 to 1.5 hours.
  • the implant substrate after soaking with the initiator solution may be washed with ethanol or acetone, and more preferably, it is washed with an ethanol-acetone solution having an ethanol content of 40% to 60% by volume.
  • the reaction of the third step in the above preparation is preferably a surface grafting reaction to a graft ratio of 5% to 20% (the reaction time is usually 0.5 to 3.0 hours), particularly 0.5 to 1.5 hours. .
  • the experimental results show that the reaction time is further extended, although the grafting rate of the monomer can be continuously increased, but the pH response coefficient does not continue to increase after reaching the peak value.
  • the illumination condition may be irradiated by ultraviolet light or the like by means of radiation or ultraviolet light irradiation, etc., which have been reported and/or used.
  • the reaction is carried out under conditions of, for example, ultraviolet light having a wavelength of 200 to 400 nm, more preferably 300 to 400 nm, such as a conventional high-pressure mercury lamp (having a wavelength of 365 nm) to increase the reaction energy and improve the reaction efficiency.
  • the washing with a solution or water as described in the above steps may be further preferably carried out simultaneously.
  • the dental implant of the present invention is coated with a pH-responsive sensitive membrane having a "switching" function in addition to the surface nanotubular structural layer on which the antimicrobial component has been loaded, and the pH-responsive sensitive membrane can be subjected to changes in the pH of the surrounding environment. And changing the characteristics of its pore filtration performance, so that the dental implant can be caused by inflammation due to its surrounding environment.
  • the pH change, and the automatic regulation and change of the controlled release and sustained release of the antibacterial component loaded in the nanotubular structure are achieved, and the antibacterial component can be provided quickly and effectively in the occurrence of inflammation, and the effective action time of the antibacterial component is prolonged. .
  • the dental implant substrate processed into titanium material by titanium or titanium alloy material is polished and surface-polished, and then ultrasonically cleaned with absolute ethanol and deionized water. After drying at 50 ° C, anodizing process is adopted.
  • a nanotube array structure layer having a pore diameter of 80 to 100 nm and a pore length of 0.1 to 0.5 ⁇ m is formed on the surface of the implant substrate, and then ultrasonically washed with absolute ethanol and deionized water, dried, and then the implant substrate is immersed in 1 M.
  • the ultraviolet light of the high-pressure mercury lamp was irradiated for 10 minutes to form a nanotube array structure layer with nano-silver antibacterial components on the surface of the dental implant substrate (the specific operation process of this example and the following examples) References: Lingzhou Zhao, et. Antibacterial nano-structured titania coating incorporated with silver nanoparticles, Biomaterials. 2011, 32, 5706-5716).
  • the implant substrate obtained in the previous step was immersed in 30 wt% oxygen water for 5 min, and then taken out, immersed in 5 wt% of silane coupling agent KH550 for 5 min, and then immersed in polyoxyethylene 500000 at 80 ° C for immersion reaction.
  • a film having a thickness of 0.8 to 1.0 mm is formed on the surface of the implant substrate, and then taken out, washed with deionized water, and dried.
  • the implant substrate prepared in the previous step is placed in an initiator solution of an ethanol solution having a benzophenone content of 0.5 M, placed in an ultraviolet reaction chamber, and 400 W in an oxygen-free environment in which nitrogen is passed. After 1 hour of high-pressure mercury lamp irradiation, ultrasonic cleaning (150-200 W) was carried out with ethanol (acetone) having an ethanol content of 50 (v)%, and dried to constant weight.
  • the implant substrate treated in the previous step was immersed in an aqueous solution of acrylic acid monomer having a content of 3.0 M, placed in an ultraviolet reaction chamber, and purged with nitrogen in a nitrogen chamber, followed by irradiation under a UV lamp at 200-250 nm. After the film surface grafting reaction was carried out, the deionized water was washed and dried under ultrasonic conditions of 150 200 W to obtain the dental implant.
  • the dental implant matrix processed into titanium material by titanium alloy material is polished on the surface, ultrasonically cleaned with absolute ethanol and deionized water, dried at 45 °C, and then anodized.
  • Body On the surface of the substrate a nanotube array structure layer having a pore diameter of 80 to 100 nm and a pore length of 0.1 to 0.5 ⁇ m is formed, and then ultrasonically washed with anhydrous ethanol and deionized water, dried, and then the implant substrate is immersed in 0.2 ⁇ silver nitrate.
  • the solution was irradiated for 20 minutes in the ultraviolet light of the high-pressure mercury lamp for 30 minutes to form a nanotube array structure layer structure loaded with the nano silver antibacterial component on the surface of the dental implant substrate.
  • the implant substrate obtained in the previous step was immersed in 30 wt% oxygen water for 30 min, and then taken out, immersed in 5 wt% of silane coupling agent KH550 for 1 min, and then immersed in a monoepoxy polyoxyethylene at 70 ° C.
  • the reaction was carried out in 100,000, and a film having a thickness of 1.0 mm was formed on the surface of the implant substrate, and then taken out, washed with deionized water, and dried.
  • the implant substrate prepared in the previous step was placed in an initiator solution of an ethanol solution having a benzophenone content of 0.3 M, placed in an ultraviolet reaction chamber, and 400 W was used in an oxygen-free environment in which nitrogen gas was passed. After the high-pressure mercury lamp was irradiated for 0.5 hour, it was washed with ethanol under 100 150 W of ultrasonic wave and dried to constant weight.
  • ⁇ The dental implant matrix processed into titanium material by pure titanium in the current conventional manner and surface polished, ultrasonically cleaned with absolute ethanol and deionized water in sequence, dried at 60 ° C, and anodized in the implant matrix
  • the surface of the nanotube array structure layer having a pore diameter of 80 to 100 nm and a pore length of 0.1 to 0.5 ⁇ m is sequentially ultrasonically cleaned with absolute ethanol and deionized water, dried, and then the implant substrate is immersed in a 0.5 ⁇ silver nitrate solution.
  • the ultraviolet light of the high-pressure mercury lamp was irradiated for 20 min to form a nanotube array structure layer structure with a nano-silver antibacterial component on the surface of the dental implant substrate.
  • the implant substrate obtained in the previous step was immersed in 30 wt% oxygen water for 30 min, and then taken out, immersed in 25 wt% silane coupling agent KH550 for 4 min, and then immersed in polyethylene glycol 20000 at 70 °C.
  • the reaction was carried out by forming a film having a thickness of 0.1 mm on the surface of the implant substrate, and then washing it with deionized water and drying it.
  • the implant substrate prepared in the previous step was placed in an initiator solution of an ethanol solution having a benzophenone content of 1.5 M, placed in an ultraviolet reaction chamber, and 400 W was used in an oxygen-free environment under a nitrogen atmosphere. After 3 hours of high-pressure mercury lamp irradiation, it was washed with acetone under 150 200 W of ultrasonic wave and dried to constant weight.
  • ⁇ The dental implant substrate processed into titanium material by pure titanium in the current conventional manner and surface polished, ultrasonically cleaned with absolute ethanol and deionized water in sequence, dried at 25 °C, and anodized in the implant matrix.
  • the surface of the nanotube array structure layer having a pore diameter of 80 to 100 nm and a pore length of 0.1 to 0.5 ⁇ m is sequentially ultrasonically cleaned with absolute ethanol and deionized water, dried, and then the implant substrate is immersed in a 1.5 M silver nitrate solution.
  • the ultraviolet light of the high pressure mercury lamp was irradiated for 10 min to form a nanotube array structure layer structure with nano silver antibacterial component on the surface of the dental implant substrate.
  • the implant substrate obtained in the previous step was immersed in 30 wt% oxygen water for 25 min, and then taken out, immersed in 10 wt% of silane coupling agent KH550 for 2 min, and then immersed in polyethylene glycol 5000 at 70 °C.
  • the reaction was carried out by forming a film having a thickness of 0.5 mm on the surface of the implant substrate, and then washing it with deionized water and drying it.
  • the implant substrate prepared in the previous step was placed in an initiator solution of an ethanol solution having a benzophenone content of 1.0 M, placed in an ultraviolet reaction chamber, and 400 W was used in an oxygen-free environment in which nitrogen gas was passed. After the high-pressure mercury lamp was irradiated for 2 hours, it was washed with an ethanol-acetone mixed solution having an ethanol content of 50 (v)% under ultrasonic conditions of 200 250 W, and dried to constant weight.
  • the dental implant substrate processed into titanium material by pure titanium in the current conventional manner and polished on the surface, ultrasonically cleaned with absolute ethanol and deionized water in sequence, dried at 30 ° C, and anodized in the implant matrix
  • a nanotube array structure layer having a pore diameter of 80 to 100 nm and a pore length of 0.1 to 0.5 ⁇ m is formed on the surface, and then ultrasonically cleaned with absolute ethanol and deionized water, dried, and then the implant substrate is immersed in a 2 ⁇ silver nitrate solution for 30 minutes.
  • the ultraviolet light of the high-pressure mercury lamp was irradiated for 30 minutes to form a nanotube array structure layer structure with a nano silver antibacterial component on the surface of the dental implant substrate.
  • the implant substrate obtained in the previous step was immersed in 30 wt% oxygen water for 20 min, and then taken out, immersed in 10 wt% of silane coupling agent KH550 for 4 min, and then immersed in polyoxyethylene 200000 at 70 ° C for reaction. A film having a thickness of 1.0 mm was formed on the surface of the implant substrate, and then taken out, washed with deionized water, and dried.
  • the implant substrate prepared in the previous step was placed in an initiator solution of an ethanol solution having a benzophenone content of 2.0 M, placed in an ultraviolet reaction chamber, and 400 W was used in an oxygen-free environment under a nitrogen atmosphere. High-pressure mercury lamp for 3 hours Thereafter, it was washed with an ethanol-acetone mixed solution having an ethanol content of 60 (v)% under ultrasonic conditions of 200 300 W, and dried to constant weight.
  • the substrate of the implant treated in the previous step was immersed in an aqueous solution of methacrylic acid having a content of 2.0 M, placed in an ultraviolet reaction chamber, and air was purged from the nitrogen chamber, followed by irradiation under a high pressure mercury lamp for 2 hours. After the grafting reaction on the surface of the membrane, the deionized water was washed and dried under ultrasonic conditions of 200 300 W to obtain the dental implant.
  • the dental implant substrate processed into titanium material by titanium alloy is polished on the surface, ultrasonically cleaned with absolute ethanol and deionized water, dried at 25 °C, and anodized in the implant.
  • a nanotube array structure layer having a pore diameter of 80 to 100 nm and a pore length of 0.1 to 0.5 ⁇ m is formed, and then ultrasonically washed with absolute ethanol and deionized water, dried, and then the implant substrate is immersed in 0.2 ⁇ silver nitrate.
  • the solution was irradiated for 5 min in the ultraviolet light of a high-pressure mercury lamp for 5 min to form a nanotube array structure layer structure with a nano-silver antibacterial component on the surface of the dental implant substrate.
  • the implant substrate obtained in the previous step was immersed in 30 wt% oxygen water for 30 min, and then taken out, immersed in 15 wt% of silane coupling agent KH550 for 3 min, and then immersed in polyethylene glycol 2000 at 80 °C.
  • the reaction was carried out by forming a film having a thickness of 0.1 mm on the surface of the implant substrate, taking it out, washing it with deionized water, and drying it.
  • the implant substrate prepared in the previous step was placed in an initiator solution of an ethanol solution having a benzophenone content of 0.1 M, placed in an ultraviolet reaction chamber, and 400 W was used in an oxygen-free environment in which nitrogen gas was passed. After the high-pressure mercury lamp was irradiated for 0.5 hour, it was washed with a 40-% ethanol-acetone mixed solution and dried to constant weight.
  • the implant substrate after the previous step was immersed in an aqueous solution of acrylic acid having a content of 1.0 M, placed in an ultraviolet reaction chamber, and purged with nitrogen in a nitrogen purge chamber, followed by irradiation under a high pressure mercury lamp for 0.5 hour. After the surface of the membrane is grafted, the deionized water is washed and dried to obtain the dental implant.
  • the surface of the nanotube array structure layer having a pore diameter of 80 to 100 nm and a pore length of 0.1 to 0.5 ⁇ m is sequentially ultrasonically cleaned with absolute ethanol and deionized water, dried, and then the implant substrate is immersed in a 1 M silver nitrate solution for 15 minutes.
  • the nano-tube array structure layer structure with the nano-silver antibacterial component is formed on the surface of the dental implant substrate by irradiating for 15 minutes.
  • the implant substrate obtained in the previous step is immersed in 30 wt% oxygen water for 5 min, and then taken out, and then immersed in 10 wt%. After reacting for 2 minutes in the silane coupling agent KH550, it was further immersed in polyethylene glycol 2000 at 80 ° C to form a film having a thickness of 0.5 mm on the surface of the implant substrate, and then taken out, and washed with deionized water. dry.
  • the implant substrate prepared in the previous step was placed in an initiator solution of an ethanol solution having a benzophenone content of 1.0 M, placed in an ultraviolet reaction chamber, and 400 W was used in an oxygen-free environment in which nitrogen gas was passed. After the high-pressure mercury lamp was irradiated for 2.0 hours, it was washed with an ethanol-acetone mixed solution having an ethanol content of 40 (v)% under ultrasonic conditions of 150 200 W, and dried to constant weight.
  • the substrate of the implant treated in the previous step was immersed in an aqueous solution of methacrylic acid having a content of 2.0 M, placed in an ultraviolet reaction chamber, and air was purged from the nitrogen chamber, followed by irradiation under a high pressure mercury lamp for 2 hours. After the grafting reaction on the surface of the membrane, the deionized water was washed and dried under ultrasonic conditions of 150 200 W to obtain the dental implant.
  • the PBS buffer solutions with pH values of 9, 7, 5, and 3 were prepared, and the dental implant products of the above Examples 2, 3, and 5 were immersed in 10 ml of PBS solution of different pH values in a dark environment for 24 hours. After removal, the Ag + concentration in the obtained PBS solution was analyzed by atomic emission spectroscopy (AES). The results are shown in Table 1.

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Abstract

提供一种智能可控释放抗菌成分的牙种植体及制备方法。所述的牙种植体，是在牙种植体表面的纳米管状结构层中负载有抗菌成分，并在该纳米管状结构层外再被覆有在聚氧乙烯膜或聚乙二醇膜表面接枝有有机单体成分所形成的pH响应敏感膜。所述有机单体成分为丙烯酸、丙烯酸铵或甲基丙烯酸的单体。该牙种植体外层的pH响应敏感膜，可根据牙种植体植入后是否出现炎症而引致的周围环境pH的不同，对纳米管状结构中所负载的抗菌成分自动实现控释和缓释的调节，以达到最好的效果，延长抗菌成分的有效作用时间。

Description

智能可控释放抗菌成分的牙种植体及制备方法 技术领域
本发明涉及一种智能可控释放抗菌成分的牙种植体及其制备方法。
背景技术
随着种植技术的发展，牙科种植体已广泛应用于临床牙缺损的治疗。种植体植入后， 其周围常伴随产生各种并发症， 炎症感染就是其中最严重和最难治疗的并发症之一。 炎 症常可因术后周围组织的感染引起，因而种植体会时刻受到细菌感染的威胁。另一方面， 种植体炎症感染后的难愈性， 还因为细菌会在种植体周围形成一层生物膜， 以阻止宿主 的防卫和抗菌剂治疗， 而且该生物膜一旦形成将很难去除。 因此， 最有效的方法是在该 生物膜形成之前就阻止细菌在种植体表面的粘附。
为此， 目前具备抗菌性能的牙种植体主要可有两类。一类是将抗菌剂结合在涂层中 涂覆在种植体表面， 并通过优化涂层的结构和抗菌剂的载量及释放率， 以使其能具有更 长时间的抗菌性能。 由于该种植体的抗菌性主要是通过涂层的降解而使抗菌剂持续缓慢 地释放，因此在种植初期由于涂层降解的缓慢，使其抗菌性能很弱甚至无有效的抗菌性。 另一类具抗菌性能的牙种植体， 如 Lingzhou Zhao, (Antibacterial nano-stmctured titania coating incorporated with silver nanoparticles Biomaterials. 2011, 32, 5706-5716) 所艮道， 通过阳极氧化或微弧氧化等方式在种植体的表面形成具有一定孔径的纳米管阵列结构， 然后将单质银或银化合物等抗菌成分或药物负载于纳米管中， 使抗菌成分逐渐释放而达 到抗菌目的。 但由于该方式对种植体表面纳米管结构中所负载抗菌剂释放的不可控性， 导致了抗菌成分在种植的初期便大量释放， 使该种植体的抗菌性能维持的时间很短。 发明内容
针对上述情况， 本发明首先提供了一种能根据种植体周围环境的变化， 对抗菌成分 进行自动控释或缓释的牙种植体， 满意地解决了目前存在的上述问题。 在此基础上， 本 发明还提供了一种所述该智能可控释放抗菌成分的牙种植体的制备方法。
本发明智能可控释放抗菌成分的牙种植体， 是在目前已有报道的在牙种植体表面形 成纳米管状结构层并负载抗菌成分 （优选为单质银或银的化合物） 的基础上， 在牙种植 体表面的纳米管状结构层外， 再被覆有在聚氧乙烯膜或聚乙二醇膜的表面接枝有有机单 体成分所形成的 ρΗ响应敏感膜。 所说的有机单体成分为丙烯酸、 丙烯酸铵或甲基丙烯 酸的单体。
实验表明， 在牙种植体表面负载有抗菌成分的纳米管状结构层外被覆的所说 pH响 应敏感膜， 可以随周围环境 pH值的变化而改变其膜孔隙的滤通性能， SP: 膜的滤通量 可随其所处环境 pH值的降低而增加， 从而能使种植体表面纳米管状结构中的抗菌成分 释放量随 pH值的变化而得到调整， 起到抗菌成分释放量可根据周围环境 pH的变化而 自动调节的"开关"作用： 在种植体未发生炎症时， 周围环境的 pH值为正常的中性， 该 pH 响应敏感膜的孔隙滤通率较低， 释放通道处于相应的"关闭"状态， 使种植体表面纳 米管状结构层中所负载的抗菌成分释放缓慢； 当种植体周围因发生炎症而使周围环境的 酸度增大至 pH<7后， 该 pH响应敏感膜的孔隙滤通率增大， 释放通道即处于"打开"的 状态， 使种植体表面纳米管状结构层中负载的抗菌成分的释放量增加， 从而提高了杀菌 效果。
试验显示， 上述结构中所说 pH响应敏感膜的厚度太厚或太薄， 对牙种植体表面纳 米管状中抗菌成分的释放会有一定的影响。 例如， 膜的厚度过大， 尽管种植体周围环境 pH值的下降可以使抗菌成分的释放通道处于"打开"状态， 但仍会对抗菌成分的释放有 一定的不利影响， 而且厚度过大时也易影响膜在牙种植体表面的被覆结合强度而容易脱 落； 如果膜的厚度过小， 当膜在牙种植体表面的被覆不均匀的情况下， 膜的厚度太小甚 至无膜存在， 其有效调控抗菌成分释放的作用就难以充分有效发挥， 易使在抗菌成分流 失。 因此， 本发明上述牙种植体所说该 pH响应敏感膜的优选厚度为 0.1~1.0mm。
进一步， 本发明上述牙种植体中所说的其表面纳米管状结构层中的纳米管状结构， 优选为孔径为 80~100nm， 孔长为 0.1~0.5μιη。
本发明上述智能可控释放抗菌成分的牙种植体的一种典型制备方法和过程，可以按 下述方式进行：
Γ: 将表层形成有纳米管状结构并在其中负载了抗菌成分后牙种植体基体， 依次 用双氧水和含量为 5~25wt%， 优选为 10~20wt%的硅烷偶联剂 KH550的乙醇溶液浸渍， 使其表面充分被覆上引发剂和偶联剂。 浸渍过程并无过多要求， 常温下进行即可。 为达 到均匀和充分的被覆，实验现实，一般在双氧水中浸渍 5-30min，优选为 10-20min即可； 在硅烷偶联剂溶液中一般可浸渍 l-5min， 优选 2-4min。干燥后， 再浸于液态或熔融态的 聚氧乙烯或聚乙二醇中反应至在种植体基体表面形成厚度为 0.1~1.0mm的膜后取出（一 般反应时间为 5~24小时）， 水洗并干燥。 其中， 所说在牙种植体基体表面形成纳米管状 结构并在其中负载了抗菌成分，可以采用包括前述文献在内的目前已有报道和 /或使用的 方式操作， 其中的抗菌成分优选为单质银或银的化合物。 所说聚氧乙烯的分子量在 100,000—7,000,000, 聚乙二醇的分子量在 2,000〜20,000范围内都是允许和可行的。
2'： 在无氧环境下， 将上步处理后的种植体基体浸泡于引发剂溶液中并进行光照 处理， 然后用乙醇或丙酮中的至少一种清洗后干燥。 所说的引发剂溶液为二苯甲酮的含 量为 0.1-2.0M, 优选为 0.1~1.0M的乙醇溶液； 所说无氧条件， 可以采用常规通入氮气 等惰性气体的方式， 以避免空气中的氧对自由基光引发剂体系所产生的阻聚作用等不利 影响。
3'：将上步处理后的种植体基体浸入含量为 1.0~6.0M，优选为 1.0 5.0M的有机单 体成分水溶液中，在无氧环境和光照条件下进行膜表面接枝反应至接枝率达膜体质量的 1%~25% (反应时间通常为 0.5-5小时）后， 水洗后干燥， 得到所说的牙种植体， 所说的 有机单体成分为丙烯酸、 丙烯酸铵或甲基丙烯酸的单体。
上述膜表面接枝的方法， 可以参考公开号 CN102250371A等文献内容的方式进行。 实验显示， 上述第 2'步中引发剂溶液浸泡的处理时间一般为 0.5-3小时即可， 优选 为 0.5-1.5小时。 用引发剂溶液浸泡处理后的种植体基体， 可以用乙醇或丙酮进行清洗， 其中更优选的是用乙醇体积含量为 40%-60%的乙醇-丙酮溶液进行清洗。
上述制备中所说第 3'步的反应， 优选为膜表面接枝反应至接枝率为 5%-20% (反应 时间通常为 0.5-3.0小时）， 特别是 0.5-1.5小时内即可完成。 实验结果显示， 反应时间的 进一步延长， 虽可继续增加单体的接枝率， 但其 pH响应系数在达到峰值后却并不会随 之继续增加。
在上述相应的光引发聚合反应和 /或接枝反应中，所说的光照条件，可以采用目前已 有报道和 /或使用的方式采用日光或紫外光照射等方式，其中优选采用以紫外光照射的条 件进行反应， 特别是以波长为 200-400nm， 更好的是 300-400nm的紫外光， 如常用的高 压汞灯 （波长为 365nm) 照射下进行反应， 以提高反应能量， 提高反应效率。
上述各步操作中所说的用溶液或用水进行的清洗， 还可进一步优选为在同时施以
100-300W, 优选为 150 250W超声波条件下的清洗， 以提高清洗的质量和效率。
如上述，本发明的牙种植体由于在已负载了抗菌成分的表面纳米管状结构层外又被 覆了具有"开关"作用的 pH响应敏感膜，利用该 pH响应敏感膜可受周围环境 pH的变化 而改变其孔隙滤通性能的特点， 使牙种植体可以根据其周围环境是否因出现炎症而引起 的 pH变化，而实现自动调节和改变其纳米管状结构中所负载的抗菌成分的控释和缓释， 达到了能在发生炎症时迅速有效地提供抗菌成分， 并延长了抗菌成分的有效作用时间。
以下通过实施例的具体实施方式再对本发明的上述内容作进一步的详细说明。但不 应将此理解为本发明上述主题的范围仅限于以下的实例。在不脱离本发明上述技术思想 情况下， 根据本领域普通技术知识和惯用手段做出的各种替换或变更， 均应包括在本发 明的范围内。
具体实施方式
实施例 1
Γ: 以钛或钛合金材料按目前常规方式加工成钛材料的牙种植体基体并表面抛光， 依次用无水乙醇和去离子水超声清洗干净， 50°C条件下干燥后， 采用阳极氧化工艺在种 植体基体表面形成孔径为 80~100nm， 孔长为 0.1~0.5μιη的纳米管阵列结构层， 再依次 用无水乙醇和去离子水超声清洗干净， 烘干， 然后将种植体基体浸入 1M硝酸银溶液 lOmin中， 在高压汞灯的紫外光中照射 10min， 使牙种植体基体表面形成负载有纳米银 抗菌成分的纳米管阵列结构层结构 （本例及以下各例的具体操作过程， 均可参考文献： Lingzhou Zhao, et. Antibacterial nano-structured titania coating incorporated with silver nanoparticles, Biomaterials. 2011, 32, 5706-5716)。
2'： 将上步得到的种植体基体浸入 30wt% 氧水中 5min后取出， 接着浸泡于 5wt% 的硅烷偶联剂 KH550中反应 5min后， 再浸泡于 80°C的聚氧乙烯 500000中浸泡反应， 在种植体基体的表面形成厚度为 0.8~1.0mm的膜后取出， 用去离子水清洗干净， 干燥。
3'： 将上步处理后的种植体基体放入二苯甲酮含量为 0.5M 的乙醇溶液的引发剂溶 液中， 置于紫外反应箱内， 在通入氮气的无氧环境下， 用 400W的高压汞灯照射 1小时 后， 用乙醇含量为 50(v)%的乙醇 -丙酮进行超声清洗 （150~200W)， 并干燥至恒重。
4'： 将上步处理后的种植体基体浸入含量为 3.0M 的丙烯酸单体水溶液中， 放入 紫外反应箱内， 通入氮气排除箱内空气， 随后在 200-250nm紫外灯下照射反应 3小时， 进行膜表面接枝反应后， 去离子水在 150 200W超声波条件下清洗并烘干， 得到所说的 牙种植体。
实施例 2
Γ: 以钛合金材料按目前常规方式加工成钛材料的牙种植体基体并表面抛光， 依次 用无水乙醇和去离子水超声清洗干净， 45 °C条件下干燥后， 采用阳极氧化工艺在种植体 基体表面形成孔径为 80~100nm， 孔长为 0.1~0.5μιη的纳米管阵列结构层， 再依次用无 水乙醇和去离子水超声清洗干净，烘干，然后将种植体基体浸入 0.2Μ硝酸银溶液 30min 中， 在高压汞灯的紫外光中照射 20min， 使牙种植体基体表面形成负载有纳米银抗菌成 分的纳米管阵列结构层结构。
2'：将上步得到的种植体基体浸入 30wt% 氧水中 30min后取出，接着浸泡于 5wt% 的硅烷偶联剂 KH550中反应 lmin后， 再浸泡于 70°C的单环氧基聚氧乙烯 100000中反 应， 在种植体基体的表面形成厚度为 1.0mm的膜后取出， 用去离子水清洗干净， 干燥。
3'： 将上步处理后的种植体基体放入二苯甲酮含量为 0.3M 的乙醇溶液的引发剂溶 液中， 置于紫外反应箱内， 在通入氮气的无氧环境下， 用 400W的高压汞灯照射 0.5小 时后， 用乙醇在 100 150W超声波条件下清洗， 并干燥至恒重。
4'： 将上步处理后的种植体基体浸入含量为 1.0M 的丙烯酸铵的水溶液中， 放入紫 外反应箱内， 通入氮气排除箱内空气， 随后在高压汞灯下照射反应 1小时， 进行膜表面 接枝反应后， 去离子水在 100 150W超声波条件下清洗并烘干， 得到所说的牙种植体。 实施例 3
Γ: 以纯钛按目前常规方式加工成钛材料的牙种植体基体并表面抛光， 依次用无水 乙醇和去离子水超声清洗干净， 60°C条件下干燥后， 采用阳极氧化工艺在种植体基体表 面形成孔径为 80~100nm， 孔长为 0.1~0.5μιη的纳米管阵列结构层， 再依次用无水乙醇 和去离子水超声清洗干净， 烘干， 然后将种植体基体浸入 0.5Μ硝酸银溶液 15min中， 在高压汞灯的紫外光中照射 20min， 使牙种植体基体表面形成负载有纳米银抗菌成分的 纳米管阵列结构层结构。
2'：将上步得到的种植体基体浸入 30wt% 氧水中 30min后取出，接着浸泡于 25wt% 的硅烷偶联剂 KH550中反应 4min后，， 再浸泡于 70 °C的聚乙二醇 20000中反应， 在种 植体基体的表面形成厚度为 0.1mm的膜后取出， 用去离子水清洗干净， 干燥。
3'： 将上步处理后的种植体基体放入二苯甲酮含量为 1.5M 的乙醇溶液的引发剂溶 液中， 置于紫外反应箱内， 在通入氮气的无氧环境下， 用 400W的高压汞灯照射 3小时 后， 用丙酮在 150 200W超声波条件下清洗， 并干燥至恒重。
4'： 将上步处理后的种植体基体浸入含量为 5.0M的丙烯酸的水溶液中， 放入紫外 反应箱内， 通入氮气排除箱内空气， 随后在高压汞灯下照射反应 0.5小时， 进行膜表面 接枝反应后， 去离子水在 150 200W超声波条件下清洗并烘干， 得到所说的牙种植体。 实施例 4
Γ: 以纯钛按目前常规方式加工成钛材料的牙种植体基体并表面抛光， 依次用无水 乙醇和去离子水超声清洗干净， 25 °C条件下干燥后， 采用阳极氧化工艺在种植体基体表 面形成孔径为 80~100nm， 孔长为 0.1~0.5μιη的纳米管阵列结构层， 再依次用无水乙醇 和去离子水超声清洗干净， 烘干， 然后将种植体基体浸入 1.5M硝酸银溶液 15min中， 在高压汞灯的紫外光中照射 10min， 使牙种植体基体表面形成负载有纳米银抗菌成分的 纳米管阵列结构层结构。
2'：将上步得到的种植体基体浸入 30wt% 氧水中 25min后取出，接着浸泡于 10wt% 的硅烷偶联剂 KH550中反应 2min后，，再浸泡于 70°C的聚乙二醇 5000中反应，在种植 体基体的表面形成厚度为 0.5mm的膜后取出， 用去离子水清洗干净， 干燥。
3'： 将上步处理后的种植体基体放入二苯甲酮含量为 1.0M 的乙醇溶液的引发剂溶 液中， 置于紫外反应箱内， 在通入氮气的无氧环境下， 用 400W的高压汞灯照射 2小时 后， 用乙醇含量为 50(v)%的乙醇-丙酮混合溶液在 200 250W超声波条件下清洗， 并干 燥至恒重。
4'： 将上步处理后的种植体基体浸入含量为 5.0M的丙烯酸铵的水溶液中， 放入紫 外反应箱内， 通入氮气排除箱内空气， 随后在高压汞灯下照射反应 2小时， 进行膜表面 接枝反应后， 去离子水在 200 250W超声波条件下清洗并烘干， 得到所说的牙种植体。 实施例 5
Γ: 以纯钛按目前常规方式加工成钛材料的牙种植体基体并表面抛光， 依次用无水 乙醇和去离子水超声清洗干净， 30°C条件下干燥后， 采用阳极氧化工艺在种植体基体表 面形成孔径为 80~100nm， 孔长为 0.1~0.5μιη的纳米管阵列结构层， 再依次用无水乙醇 和去离子水超声清洗干净， 烘干， 然后将种植体基体浸入 2Μ硝酸银溶液 30min中， 在 高压汞灯的紫外光中照射 30min， 使牙种植体基体表面形成负载有纳米银抗菌成分的纳 米管阵列结构层结构。
2'：将上步得到的种植体基体浸入 30wt% 氧水中 20min后取出，接着浸泡于 10wt% 的硅烷偶联剂 KH550中反应 4min后，，再浸泡于 70°C的聚氧乙烯 200000中反应，在种 植体基体的表面形成厚度为 1.0mm的膜后取出， 用去离子水清洗干净， 干燥。
3'： 将上步处理后的种植体基体放入二苯甲酮含量为 2.0M 的乙醇溶液的引发剂溶 液中， 置于紫外反应箱内， 在通入氮气的无氧环境下， 用 400W的高压汞灯照射 3小时 后， 用乙醇含量为 60(v)%的乙醇-丙酮混合溶液在 200 300W超声波条件下清洗， 并干 燥至恒重。
4'： 将上步处理后的种植体基体浸入含量为 2.0M的甲基丙烯酸的水溶液中， 放入 紫外反应箱内， 通入氮气排除箱内空气， 随后在高压汞灯下照射反应 2小时， 进行膜表 面接枝反应后，去离子水在 200 300W超声波条件下清洗并烘干，得到所说的牙种植体。 实施例 6
Γ: 以钛合金按目前常规方式加工成钛材料的牙种植体基体并表面抛光， 依次用无 水乙醇和去离子水超声清洗干净， 25 °C条件下干燥后， 采用阳极氧化工艺在种植体基体 表面形成孔径为 80~100nm， 孔长为 0.1~0.5μιη的纳米管阵列结构层， 再依次用无水乙 醇和去离子水超声清洗干净， 烘干， 然后将种植体基体浸入 0.2Μ硝酸银溶液 5min中， 在高压汞灯的紫外光中照射 5min， 使牙种植体基体表面形成负载有纳米银抗菌成分的 纳米管阵列结构层结构。
2'：将上步得到的种植体基体浸入 30wt% 氧水中 30min后取出，接着浸泡于 15wt% 的硅烷偶联剂 KH550中反应 3min后，，再浸泡于 80°C的聚乙二醇 2000中反应，在种植 体基体的表面形成厚度为 0.1mm的膜后取出， 用去离子水清洗干净， 干燥。
3'： 将上步处理后的种植体基体放入二苯甲酮含量为 0.1M 的乙醇溶液的引发剂溶 液中， 置于紫外反应箱内， 在通入氮气的无氧环境下， 用 400W的高压汞灯照射 0.5小 时后， 用乙醇含量为 40( ％的乙醇-丙酮混合溶液清洗， 并干燥至恒重。
4'： 将上步处理后的种植体基体浸入含量为 1.0M的丙烯酸的水溶液中， 放入紫外 反应箱内， 通入氮气排除箱内空气， 随后在高压汞灯下照射反应 0.5小时， 进行膜表面 接枝反应后， 去离子水进行清洗并烘干， 得到所说的牙种植体。
实施例 7
Γ: 以纯钛按目前常规方式加工成钛材料的牙种植体基体并表面抛光， 依次用无水 乙醇和去离子水超声清洗干净， 25 °C条件下干燥后， 采用阳极氧化工艺在种植体基体表 面形成孔径为 80~100nm， 孔长为 0.1~0.5μιη的纳米管阵列结构层， 再依次用无水乙醇 和去离子水超声清洗干净， 烘干， 然后将种植体基体浸入 1M硝酸银溶液 15min中， 在 高压汞灯的紫外光中照射 15min， 使牙种植体基体表面形成负载有纳米银抗菌成分的纳 米管阵列结构层结构。
2'：将上步得到的种植体基体浸入 30wt% 氧水中 5min后取出，接着浸泡于 10wt% 的硅烷偶联剂 KH550中反应 2min后，，再浸泡于 80°C的聚乙二醇 2000中反应，在种植 体基体的表面形成厚度为 0.5mm的膜后取出， 用去离子水清洗干净， 干燥。
3'： 将上步处理后的种植体基体放入二苯甲酮含量为 1.0M 的乙醇溶液的引发剂溶 液中， 置于紫外反应箱内， 在通入氮气的无氧环境下， 用 400W的高压汞灯照射 2.0小 时后， 用乙醇含量为 40(v)%的乙醇-丙酮混合溶液在 150 200W超声波条件下清洗， 并 干燥至恒重。
4'： 将上步处理后的种植体基体浸入含量为 2.0M的甲基丙烯酸的水溶液中， 放入 紫外反应箱内， 通入氮气排除箱内空气， 随后在高压汞灯下照射反应 2小时， 进行膜表 面接枝反应后，去离子水在 150 200W超声波条件下清洗并烘干，得到所说的牙种植体。
配制 pH值分别为 9、 7、 5、 3的 PBS缓冲溶液， 将上述实施例 2、 3、 5的牙种植 体产品在黑暗环境下， 分别浸泡于各不同 pH值的 PBS溶液 10ml中， 24h后取出， 用 原子发射光谱 （AES) 分析所得 PBS溶液中的 Ag+浓度。 结果如表 1所示。
表 1结果清楚显示， 本发明的牙种植体， 可以随其所处周围环境 pH值的降低而自 动增加抗菌成分 （Ag+) 的释放量， 能实现对抗菌成分的智能控释目的。
表 1 牙种植体在不同 pH值 PBS溶液中的 Ag+释放量 （单位： ppm)
Figure imgf000009_0001

Claims

权利要求书
1. 智能可控释放抗菌成分的牙种植体， 在牙种植体表面的纳米管状结构层 中负载有抗菌成分， 其特征是在牙种植体纳米管状结构层外， 被覆有在聚氧乙烯 膜或聚乙二醇膜表面接枝有有机单体成分所形成的 pH响应敏感膜， 所说的有机 单体成分为丙烯酸、 丙烯酸铵或甲基丙烯酸的单体。
2. 如权利要求 1所述的牙种植体， 其特征是所说的 pH响应敏感膜厚度为 0.1〜1.0mm。
3. 如权利要求 1所述的牙种植体， 其特征是所说纳米管状结构层中的纳米 管状结构的孔径为 80〜100nm， 孔长为 0.1〜0.5μιη。
4. 如权利要求 1至 3之一所述的牙种植体， 其特征是所说纳米管状结构层 中负载的抗菌成分为银单质或银的化合物。
5. 制备权利要求 1至 4之一所述智能可控释放抗菌成分的牙种植体的方法， 其特征是按下述方式进行：
Γ : 将表层形成有纳米管状结构并在其中负载了抗菌成分的牙种植体基 体， 依次用双氧水和含量为 5〜25wt%， 优选为 10〜20wt%的硅烷偶联剂 KH550 的乙醇溶液浸渍后， 干燥， 再浸于液态或熔融态的聚氧乙烯或聚乙二醇中反应至 在种植体基体表面形成厚度为 0.1〜1.0mm的膜后取出， 水洗并干燥；
2'： 在无氧环境下， 将上步处理后的种植体基体浸泡于引发剂溶液中并进 行光照处理， 然后用乙醇或丙酮中的至少一种清洗后干燥， 所说的引发剂溶液为 二苯甲酮含量为 0.1〜2.0M， 优选为 0.1〜1.0M的乙醇溶液；
3'： 将上步处理后的种植体基体浸入含量为 1.0〜6.0M， 优选为 1.0〜5.0M 的有机单体成分水溶液中，在无氧环境和光照条件下进行膜表面接枝反应至接枝 率达膜体质量的 1%〜25%后， 水洗后干燥， 得到所说的牙种植体， 所说的有机 单体成分为丙烯酸、 丙烯酸铵或甲基丙烯酸的单体。
6. 如权利要求 5所述的制备方法， 其特征是所说第 2'步引发剂溶液的浸泡 处理时间为 0.5〜3小时， 优选为 0.5〜1.5小时。
7. 如权利要求 5所述的制备方法， 其特征是所说第 2'步引发剂溶液浸泡处 理后的种植体基体， 用乙醇体积含量为 40%〜60%的乙醇-丙酮溶液清洗。
8. 如权利要求 5所述的制备方法，其特征是所说第 3'步的反应的膜表面接 枝反应至接枝率为 5%〜20%。
9. 如权利要求 5所述的制备方法，其特征是所说的光照条件为紫外光照射， 优选波长为波长 200〜400nm的紫外光照射。
10.如权利要求 5至 9之一所述的制备方法，其特征是所说各步中的清洗为 在同时施以 100〜300W， 优选为 150〜250W超声波条件下的清洗。
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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN113952511A (zh) * 2021-09-30 2022-01-21 中山大学附属口腔医院 一种于钛基材料表面构建防污抗菌涂层的方法及其应用

Families Citing this family (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102846386B (zh) * 2012-09-19 2015-02-25 四川大学 智能可控释放抗菌成分的牙种植体及制备方法
CN106512106A (zh) * 2016-11-02 2017-03-22 北京大学口腔医学院 抗菌牙科材料及其制备方法
CN108354681A (zh) * 2018-03-08 2018-08-03 南京医科大学附属口腔医院 一种含银钛合金根管内固位、根尖封闭一体化牙胶尖
CN109589454A (zh) * 2018-11-13 2019-04-09 佛山市安齿生物科技有限公司 一种用于牙种植体或骨科器械的抗菌药物缓释系统的构建方法
CN110859997B (zh) * 2018-12-20 2020-06-23 四川大学 具有成骨-抗炎-血糖三维响应结构的牙种植体及其制备方法

Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6306422B1 (en) * 1994-02-01 2001-10-23 Caphco, Inc. Compositions and devices for controlled release of active ingredients
CN1929819A (zh) * 2004-01-30 2007-03-14 考里安国际公司 递送活性剂的快速溶解膜
CN101193627A (zh) * 2005-07-12 2008-06-04 赢创罗姆有限责任公司 部分中和的阴离子（甲基）丙烯酸酯共聚物作为包衣用于制备在降低的pH值下释放活性物质的药物剂型的应用
CN101744666A (zh) * 2010-01-01 2010-06-23 东南大学 微量元素硒缓释功能性的人工牙根及其制备方法
WO2011042897A1 (en) * 2009-10-05 2011-04-14 Yissum Research Development Company Of The Hebrew University Of Jerusalem, Ltd Liquid precursor compositions and uses thereof for a ph-dependant sustained release treatment of oral disorders
CN102202700A (zh) * 2008-09-08 2011-09-28 罗维实验室制药股份公司 聚合材料
CN102250371A (zh) * 2010-05-21 2011-11-23 张永昶 两步光接枝法制备pH敏感膜
CN102846386A (zh) * 2012-09-19 2013-01-02 四川大学 智能可控释放抗菌成分的牙种植体及制备方法

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7901462B2 (en) * 2005-06-23 2011-03-08 Depuy Products, Inc. Implants with textured surface and methods for producing the same
DE102009023459B4 (de) * 2009-06-02 2017-08-31 Aap Implantate Ag Osteosynthese mit Nanosilber
CN102383163A (zh) * 2010-08-27 2012-03-21 上海交通大学医学院附属第九人民医院 钛种植体表面可控二氧化钛纳米管仿生修饰方法及种植体

Patent Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6306422B1 (en) * 1994-02-01 2001-10-23 Caphco, Inc. Compositions and devices for controlled release of active ingredients
CN1929819A (zh) * 2004-01-30 2007-03-14 考里安国际公司 递送活性剂的快速溶解膜
CN101193627A (zh) * 2005-07-12 2008-06-04 赢创罗姆有限责任公司 部分中和的阴离子（甲基）丙烯酸酯共聚物作为包衣用于制备在降低的pH值下释放活性物质的药物剂型的应用
CN102202700A (zh) * 2008-09-08 2011-09-28 罗维实验室制药股份公司 聚合材料
WO2011042897A1 (en) * 2009-10-05 2011-04-14 Yissum Research Development Company Of The Hebrew University Of Jerusalem, Ltd Liquid precursor compositions and uses thereof for a ph-dependant sustained release treatment of oral disorders
CN101744666A (zh) * 2010-01-01 2010-06-23 东南大学 微量元素硒缓释功能性的人工牙根及其制备方法
CN102250371A (zh) * 2010-05-21 2011-11-23 张永昶 两步光接枝法制备pH敏感膜
CN102846386A (zh) * 2012-09-19 2013-01-02 四川大学 智能可控释放抗菌成分的牙种植体及制备方法

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN113952511A (zh) * 2021-09-30 2022-01-21 中山大学附属口腔医院 一种于钛基材料表面构建防污抗菌涂层的方法及其应用
CN113952511B (zh) * 2021-09-30 2023-05-09 中山大学附属口腔医院 一种于钛基材料表面构建防污抗菌涂层的方法及其应用

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