CN113398337A - Spinal internal fixation device containing artificial bone carrier implanted with antituberculosis drugs in sustained release manner - Google Patents

Spinal internal fixation device containing artificial bone carrier implanted with antituberculosis drugs in sustained release manner Download PDF

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Publication number
CN113398337A
CN113398337A CN202110698560.9A CN202110698560A CN113398337A CN 113398337 A CN113398337 A CN 113398337A CN 202110698560 A CN202110698560 A CN 202110698560A CN 113398337 A CN113398337 A CN 113398337A
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drug
artificial bone
fixation device
rifampicin
internal fixation
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孙雯雯
张青
范琳
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Shanghai Pulmonary Hospital
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Shanghai Pulmonary Hospital
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/54Biologically active materials, e.g. therapeutic substances
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B17/00Surgical instruments, devices or methods, e.g. tourniquets
    • A61B17/56Surgical instruments or methods for treatment of bones or joints; Devices specially adapted therefor
    • A61B17/58Surgical instruments or methods for treatment of bones or joints; Devices specially adapted therefor for osteosynthesis, e.g. bone plates, screws, setting implements or the like
    • A61B17/68Internal fixation devices, including fasteners and spinal fixators, even if a part thereof projects from the skin
    • A61B17/70Spinal positioners or stabilisers ; Bone stabilisers comprising fluid filler in an implant
    • A61B17/7001Screws or hooks combined with longitudinal elements which do not contact vertebrae
    • A61B17/7002Longitudinal elements, e.g. rods
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B17/00Surgical instruments, devices or methods, e.g. tourniquets
    • A61B17/56Surgical instruments or methods for treatment of bones or joints; Devices specially adapted therefor
    • A61B17/58Surgical instruments or methods for treatment of bones or joints; Devices specially adapted therefor for osteosynthesis, e.g. bone plates, screws, setting implements or the like
    • A61B17/68Internal fixation devices, including fasteners and spinal fixators, even if a part thereof projects from the skin
    • A61B17/70Spinal positioners or stabilisers ; Bone stabilisers comprising fluid filler in an implant
    • A61B17/7049Connectors, not bearing on the vertebrae, for linking longitudinal elements together
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02Prostheses implantable into the body
    • A61F2/30Joints
    • A61F2/44Joints for the spine, e.g. vertebrae, spinal discs
    • A61F2/4455Joints for the spine, e.g. vertebrae, spinal discs for the fusion of spinal bodies, e.g. intervertebral fusion of adjacent spinal bodies, e.g. fusion cages
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/02Inorganic materials
    • A61L27/12Phosphorus-containing materials, e.g. apatite
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/14Macromolecular materials
    • A61L27/18Macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02Prostheses implantable into the body
    • A61F2/30Joints
    • A61F2002/30001Additional features of subject-matter classified in A61F2/28, A61F2/30 and subgroups thereof
    • A61F2002/30621Features concerning the anatomical functioning or articulation of the prosthetic joint
    • A61F2002/30622Implant for fusing a joint or bone material
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L2300/00Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/10Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing inorganic materials
    • A61L2300/112Phosphorus-containing compounds, e.g. phosphates, phosphonates
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L2300/00Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/40Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
    • A61L2300/404Biocides, antimicrobial agents, antiseptic agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L2300/00Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/40Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
    • A61L2300/412Tissue-regenerating or healing or proliferative agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L2300/00Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/60Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a special physical form
    • A61L2300/602Type of release, e.g. controlled, sustained, slow
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L2430/00Materials or treatment for tissue regeneration
    • A61L2430/02Materials or treatment for tissue regeneration for reconstruction of bones; weight-bearing implants

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  • Health & Medical Sciences (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Neurology (AREA)
  • Transplantation (AREA)
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  • Oral & Maxillofacial Surgery (AREA)
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  • Heart & Thoracic Surgery (AREA)
  • Molecular Biology (AREA)
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Abstract

The invention discloses a spinal internal fixation device containing a drug slow-release implantation artificial bone carrier, which comprises fixing screws arranged at intervals and a connecting rod for connecting the two fixing screws, wherein tuberculosis treatment drugs are arranged inside the fixing screws and/or inside the connecting rod, drug passing holes for releasing the tuberculosis treatment drugs are arranged on the outer walls of the fixing screws and the outer wall of the connecting rod, positioning devices for fixing the tuberculosis treatment drugs are arranged inside the fixing screws and inside the connecting rod, and the tuberculosis treatment drugs comprise a slow-release drug carrier, isoniazid, rifampicin and streptomycin.

Description

Spinal internal fixation device containing artificial bone carrier implanted with antituberculosis drugs in sustained release manner
Technical Field
The invention relates to the technical field of medical treatment, in particular to a spinal internal fixation device containing an artificial bone carrier implanted with antituberculosis drugs in a sustained-release manner.
Background
Osteoarticular tuberculosis is a specific bone-and-joint infection caused by mycobacterium tuberculosis, accounting for about five to ten percent of systemic tuberculosis infections, with spinal tuberculosis being the most common form. Antituberculosis drugs are the basis for the treatment of osteoarticular tuberculosis.
Methods for treating osteoarticular tuberculosis can be broadly divided into medicinal systemic treatment and local surgical treatment. The purpose of surgical treatment is mainly to remove dead bones and tuberculous abscesses to relieve nerve compression and maintain spinal stability. However, although the surgical operation can remove local tuberculosis focus, the tuberculosis infection can not be completely and completely removed, and postoperative patients still need to take antituberculosis drugs for a long time. The drug therapy is the treatment basis of the osteoarticular tuberculosis, and the traditional drug therapy can be divided into oral administration, intramuscular injection, intravenous drip and the like. The above methods all reach the focus through blood circulation to achieve the purpose of killing tubercle bacillus, but the pathogenesis of osteoarticular tuberculosis determines that tubercle bacillus forms a large amount of pus, cheese-like necrotic tissues, dead bones and hardened bones at the focus, and the disorder of local pathological structures causes insufficient blood supply of the focus, so that the medicament cannot reach the Minimum Inhibitory Concentration (MIC) of the tubercle bacillus in the tuberculosis focus, namely the effective bactericidal concentration, and the continuous low medicament concentration even induces the occurrence of medicament resistance. At present, a Chinese patent No. CN104107086B discloses a pedicle screw with a drug dosage accurate slow release function, which has a certain drug dosage slow release function, but the patent utilizes a body temperature-memory alloy control as a starting and releasing control device, the slow release time is short, when the body temperature-memory alloy control works, the body temperature-memory alloy control can completely release the drug in a short time, a drug-carrying system can not stably release the drug for a long time, the drug concentration can not be stably formed at a tuberculosis focus for a long time, mycobacterium tuberculosis can not be thoroughly killed, and even drug resistance is induced.
Disclosure of Invention
The present invention is directed to solving the above-mentioned problems by providing an internal spinal fixation device comprising an artificial bone carrier into which an anti-tubercular drug is slowly released.
The technical problem solved by the invention can be realized by adopting the following technical scheme:
the utility model provides a spinal internal fixation device who contains artifical bone carrier is implanted in slow release of antituberculosis medicine, includes the set screw that the interval set up and connect two set screw's connecting rod, its characterized in that, set screw inside and/or the inside tuberculosis treatment medicine that is provided with of connecting rod, set screw outer wall and connecting rod outer wall are provided with the medicine hole of crossing that supplies the release of tuberculosis treatment medicine, set screw inside and the inside positioner that is used for fixed tuberculosis treatment medicine that sets up of connecting rod, tuberculosis treatment medicine includes slow-release medicine carrier, isoniazid, rifampin, streptomycin.
In a preferred embodiment of the present invention, the sustained-release drug carrier comprises PLGA, a polylactic-co-glycolic acid polymer.
In a preferred embodiment of the present invention, the weight ratio of streptomycin, isoniazid, rifampin, PLGA, PVA is 240-: 35-45: 55-65: 90-110: 550-650.
In a preferred embodiment of the present invention, the weight ratio of streptomycin, isoniazid, rifampin, PLGA, PVA is 250: 40: 60: 100: 600.
in a preferred embodiment of the invention, the tuberculosis treatment drug is prepared by a double emulsion solvent volatilization method, and comprises the following steps:
1) weighing streptomycin, isoniazid, rifampicin, polylactic-co-glycolic acid polymer PLGA and polyvinyl alcohol PVA according to the weight ratio;
2) dissolving isoniazid and streptomycin in distilled water, and fully and uniformly oscillating to form an internal water phase;
3) dissolving polyvinyl alcohol PVA in distilled water, and heating in boiling water to dissolve completely;
4) putting rifampicin in dichloromethane to fully dissolve to form an oil phase;
5) after the preparation of the materials is finished, putting the materials into a refrigerator to be cooled to be ice-cold, and storing the materials in the dark as far as possible in the whole process;
6) pouring the oil phase into the aqueous phase, shaking with smashing the appearance and dissolving, pouring the mixed solution that makes into polyvinyl alcohol PVA solution fast, wrapping up the container with black plastic paper, avoiding rifampicin to see light and decomposing, then rapid mixing, whether take a small amount of solution to observe under the microscope after a period and have the microballon to generate, continuously stir 2-4 hours, wait that dichloromethane volatilizees totally, stop the stirring, with centrifuge centrifugal washing, filter parallel freeze drying handles, the low temperature preservation of keeping out of the sun.
In a preferred embodiment of the invention, the tuberculosis treatment drug is prepared by a double emulsion solvent volatilization method, and comprises the following steps:
1) weighing 250mg of streptomycin, 40mg of isoniazide, 60mg of rifampicin, 100mg of polylactic-co-glycolic acid polymer PLGA and polyvinyl alcohol PVA600mg according to the weight ratio;
2) dissolving isoniazid and streptomycin in 2ml of distilled water, and fully and uniformly oscillating by using a vortex oscillator to form an internal water phase;
3) dissolving polyvinyl alcohol PVA in 30ml of distilled water, and heating the solution in boiling water until the solution is fully dissolved;
4) putting rifampicin in 3ml dichloromethane to fully dissolve to form an oil phase;
5) after the preparation of the materials is finished, putting the materials into a refrigerator with the temperature of 4 ℃ for cooling to be cold, and storing the materials in the dark as far as possible in the whole process;
6) pouring the water phase into the oil phase, shaking with the ultrasonic crusher and dissolving for 1 minute, pouring the prepared mixed solution into polyvinyl alcohol PVA solution fast, wrapping the container with black plastic paper, avoiding rifampicin to see light and decompose, adding magnetic stirrer and stirring fast, the rotational speed is 2000rpm/min, take a small amount of solution after 30 minutes and observe under the microscope whether there is the microballon to generate, stir 3 hours continuously, wait that dichloromethane volatilizes completely, stop the stirring, centrifuge centrifugal washing, filter and freeze-dry the processing parallelly, keep in the dark place at low temperature.
In a preferred embodiment of the present invention, the positioning device comprises compression springs disposed inside the fixing screw and inside the connecting rod, and a pressing plate connected to the compression springs, the pressing plate pressing the tuberculosis treatment drug so that the tuberculosis treatment drug is always located at one side of the drug passing hole.
In a preferred embodiment of the invention, both the fixation screw and the connecting rod are made of tricalcium phosphate β -TCP composite.
In a preferred embodiment of the invention, the compression spring and the tablet are both made of tricalcium phosphate beta-TCP composite.
By adopting the technical scheme, the anti-tuberculosis drug can be slowly and durably released through the artificial bone drug loading, the local drug concentration is increased, meanwhile, the focal local bone defect can be repaired, the osseous fusion is promoted, and the sustained release of weeks and even months can be maintained by controlling the local release speed of the tuberculosis treatment drug.
Drawings
In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings used in the description of the embodiments or the prior art will be briefly described below, it is obvious that the drawings in the following description are only some embodiments of the present invention, and for those skilled in the art, other drawings can be obtained according to the drawings without creative efforts.
Fig. 1 is a schematic structural diagram of an embodiment of the present invention.
Detailed Description
In order to make the technical means, the creation characteristics, the achievement purposes and the effects of the invention easy to understand, the invention is further explained below.
Referring to fig. 1, the spinal internal fixation device including the slow release implantation of the anti-tuberculosis drug into the artificial bone carrier includes fixing screws 100 arranged at intervals and a connecting rod 200 connecting the two fixing screws 100, wherein the two fixing screws 100 are distributed at both sides of a tuberculosis focus a of the spinal 1. The set screw 100 and the connecting rod 200 are both made of tricalcium phosphate beta-TCP composite. The tricalcium phosphate beta-TCP composite material is a degradable biological material with excellent biocompatibility and good biomechanical property, can provide elements such as calcium, phosphorus and the like for the formation of new bones while degrading, promotes the formation of the new bones, and is widely applied to the field of biomedicine, particularly tissue engineering research. Tricalcium phosphate beta-TCP composite material is an ideal bone repair material.
The tuberculosis treatment drug 300 is disposed inside the set screw 100 and/or inside the connection rod 200. The interior of the fixing screw 100 and the interior of the connecting rod 200 in this embodiment are provided with tuberculosis treatment drugs 300. The outer walls of the fixing screw 100 and the connecting rod 200 are provided with drug passing holes 400 for releasing the tuberculosis treatment drug 300. The tuberculosis treatment drug 300 comprises a slow release drug carrier, isoniazid, rifampicin and streptomycin, wherein the slow release drug carrier comprises polylactic-co-glycolic acid polymer PLGA, and the polylactic-co-glycolic acid polymer PLGA has the advantages of large drug loading capacity, long drug release time, adjustable degradation time and the like. Streptomycin (Sm), Isoniazid (INH) and Rifampicin (RFP) are three first-line antituberculosis drugs commonly used in clinic at present, streptomycin is more commonly used for intraoperative local spraying by orthopedists, and isoniazid and rifampicin are the most effective first-line antituberculosis drugs.
The weight ratio of streptomycin, isoniazid, rifampicin, polylactic-co-glycolic acid polymer PLGA and polyvinyl alcohol PVA is 240-: 35-45: 55-65: 90-110: 550-650, the weight ratio of streptomycin, isoniazid, rifampin, poly (lactic-co-glycolic acid) polymer PLGA and polyvinyl alcohol PVA in this example is 250: 40: 60: 100: 600.
the tuberculosis treatment medicine in the embodiment is prepared by a double-emulsion solvent volatilization method, and comprises the following steps:
1) weighing 250mg of streptomycin, 40mg of isoniazide, 60mg of rifampicin, 100mg of polylactic-co-glycolic acid polymer PLGA and polyvinyl alcohol PVA600mg according to the weight ratio;
2) dissolving isoniazid and streptomycin in 2ml of distilled water, and fully and uniformly oscillating by using a vortex oscillator to form an internal water phase;
3) dissolving polyvinyl alcohol PVA in 30ml of distilled water, and heating the solution in boiling water until the solution is fully dissolved;
4) putting rifampicin in 3ml dichloromethane to fully dissolve to form an oil phase;
5) after the preparation of the materials is finished, putting the materials into a refrigerator with the temperature of 4 ℃ for cooling to be cold, and storing the materials in the dark as far as possible in the whole process;
6) pouring the water phase into the oil phase, shaking with the ultrasonic crusher and dissolving for 1 minute, pouring the prepared mixed solution into polyvinyl alcohol PVA solution fast, wrapping the container with black plastic paper, avoiding rifampicin to see light and decompose, adding magnetic stirrer and stirring fast, the rotational speed is 2000rpm/min, take a small amount of solution after 30 minutes and observe under the microscope whether there is the microballon to generate, stir 3 hours continuously, wait that dichloromethane volatilizes completely, stop the stirring, centrifuge centrifugal washing, filter and freeze-dry the processing parallelly, keep in the dark place at low temperature.
The positioning device 500 for fixing the tuberculosis treatment medicine 300 is arranged inside the fixing screw 100 and the connecting rod 200, the positioning device 500 comprises a compression spring 510 arranged inside the fixing screw 100 and the connecting rod 200 and a pressing sheet 520 connected with the compression spring 510, along with the slow release of the tuberculosis treatment medicine 300, the size of the tuberculosis treatment medicine 300 is smaller and smaller, the tuberculosis treatment medicine 300 is easy to shift, and the pressing sheet 520 can compress the tuberculosis treatment medicine 300, so that the tuberculosis treatment medicine 300 is always positioned on one side of the medicine passing hole 400. The compression spring 510 and the tablet 520 in this embodiment are both made of tricalcium phosphate beta-TCP composite.
The invention can slowly and durably release the antituberculosis drug through the artificial bone drug loading, increases the local drug concentration, can repair the local bone defect of the focus, promotes the osseous fusion, and can maintain the sustained release for weeks and even months by controlling the local release speed of the tuberculosis treatment drug.
The invention has the following effects:
in a new zealand rabbit spinal tuberculosis model constructed by selecting a mycobacterium tuberculosis H37Rv standard strain in earlier stage research, compared with an artificial bone without a medicament, the artificial bone loaded with streptomycin, isoniazid and rifampicin can play a better role in bone fusion and bone repair and reconstruction while performing local slow-release treatment on a rabbit spinal tuberculosis focus, and can heal well in 12 weeks; after 12 weeks, the high performance liquid chromatography is used for detecting the local drug concentration of muscle tissues within 10mm around the drug sustained-release material, and the local concentrations of the 3 drugs are found to be 10 times higher than the minimum bacteriostatic concentration, so that the antituberculosis drugs in the material can be stably released for a long time and can be kept at effective bactericidal concentrations locally, and higher local drug concentrations can be still achieved even in 12 weeks.
The foregoing shows and describes the general principles and broad features of the present invention and advantages thereof. It will be understood by those skilled in the art that the present invention is not limited to the embodiments described above, which are described in the specification and illustrated only to illustrate the principle of the present invention, but that various changes and modifications may be made therein without departing from the spirit and scope of the present invention, which fall within the scope of the invention as claimed. The scope of the invention is defined by the appended claims and equivalents thereof.

Claims (9)

1. Contain slow-release fixing device in backbone of artificial bone carrier is implanted to antituberculosis medicine, including the set screw that the interval set up and connect two set screw's connecting rod, its characterized in that, set screw inside and/or the inside tuberculosis treatment medicine that is provided with of connecting rod, set screw outer wall and connecting rod outer wall are provided with the medicine hole of crossing that supplies the release of tuberculosis treatment medicine, set screw inside and the inside positioner that is used for fixed tuberculosis treatment medicine that sets up of connecting rod, tuberculosis treatment medicine includes slow-release medicine carrier, isoniazid, rifampin, streptomycin.
2. The spinal internal fixation device comprising an artificial bone carrier for the sustained release implantation of an antituberculous drug according to claim 1, wherein said sustained release carrier comprises PLGA.
3. The spinal internal fixation device comprising the artificial bone carrier for slow release implantation of anti-tubercular drugs in claim 2, wherein the weight ratio of streptomycin, isoniazid, rifampicin, PLGA, PVA is 240-: 35-45: 55-65: 90-110: 550-650.
4. The spinal internal fixation device comprising the artificial bone carrier for the slow release implantation of the antituberculous drug into the bone according to claim 3, wherein the weight ratio of streptomycin, isoniazid, rifampicin, poly (lactic-co-glycolic acid) polymer PLGA, polyvinyl alcohol PVA is 250: 40: 60: 100: 600.
5. the spinal internal fixation device containing the antituberculous drug slow-release implantation artificial bone carrier according to claim 3, wherein the tuberculosis treatment drug is prepared by a double emulsion solvent evaporation method, comprising the following steps:
1) weighing streptomycin, isoniazid, rifampicin, polylactic-co-glycolic acid polymer PLGA and polyvinyl alcohol PVA according to the weight ratio;
2) dissolving isoniazid and streptomycin in distilled water, and fully and uniformly oscillating to form an internal water phase;
3) dissolving polyvinyl alcohol PVA in distilled water, and heating in boiling water to dissolve completely;
4) putting rifampicin in dichloromethane to fully dissolve to form an oil phase;
5) after the preparation of the materials is finished, putting the materials into a refrigerator to be cooled to be ice-cold, and storing the materials in the dark as far as possible in the whole process;
6) pouring the oil phase into the aqueous phase, shaking with smashing the appearance and dissolving, pouring the mixed solution that makes into polyvinyl alcohol PVA solution fast, wrapping up the container with black plastic paper, avoiding rifampicin to see light and decomposing, then rapid mixing, whether take a small amount of solution to observe under the microscope after a period and have the microballon to generate, continuously stir 2-4 hours, wait that dichloromethane volatilizees totally, stop the stirring, with centrifuge centrifugal washing, filter parallel freeze drying handles, the low temperature preservation of keeping out of the sun.
6. The spinal internal fixation device containing the antituberculous drug slow-release implantation artificial bone carrier according to claim 5, wherein the tuberculosis treatment drug is prepared by a double emulsion solvent evaporation method, comprising the following steps:
1) weighing 250mg of streptomycin, 40mg of isoniazide, 60mg of rifampicin, 100mg of polylactic-co-glycolic acid polymer PLGA and polyvinyl alcohol PVA600mg according to the weight ratio;
2) dissolving isoniazid and streptomycin in 2ml of distilled water, and fully and uniformly oscillating by using a vortex oscillator to form an internal water phase;
3) dissolving polyvinyl alcohol PVA in 30ml of distilled water, and heating the solution in boiling water until the solution is fully dissolved;
4) putting rifampicin in 3ml dichloromethane to fully dissolve to form an oil phase;
5) after the preparation of the materials is finished, putting the materials into a refrigerator with the temperature of 4 ℃ for cooling to be cold, and storing the materials in the dark as far as possible in the whole process;
6) pouring the water phase into the oil phase, shaking with the ultrasonic crusher and dissolving for 1 minute, pouring the prepared mixed solution into polyvinyl alcohol PVA solution fast, wrapping the container with black plastic paper, avoiding rifampicin to see light and decompose, adding magnetic stirrer and stirring fast, the rotational speed is 2000rpm/min, take a small amount of solution after 30 minutes and observe under the microscope whether there is the microballon to generate, stir 3 hours continuously, wait that dichloromethane volatilizes completely, stop the stirring, centrifuge centrifugal washing, filter and freeze-dry the processing parallelly, keep in the dark place at low temperature.
7. The spinal internal fixation device containing an artificial bone carrier for slow release implantation of an antituberculous drug according to claim 1, wherein the positioning means comprises compression springs disposed inside the fixing screw and inside the connecting rod and a pressing plate connected to the compression springs, the pressing plate presses the tuberculous therapeutic drug so that the tuberculous therapeutic drug is always located at one side of the drug passing hole.
8. The spinal internal fixation device comprising an artificial bone carrier for the slow release implantation of an anti-tubercular drug according to claim 1, wherein the fixation screw and the connection rod are both made of tricalcium phosphate β -TCP composite.
9. The spinal internal fixation device comprising an artificial bone carrier for the sustained release implantation of an antituberculous drug according to claim 7, wherein the compression spring and the compression plate are both made of tricalcium phosphate β -TCP composite.
CN202110698560.9A 2021-06-23 2021-06-23 Spinal internal fixation device containing artificial bone carrier implanted with antituberculosis drugs in sustained release manner Pending CN113398337A (en)

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Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1571663A (en) * 2001-10-19 2005-01-26 伊莱利利公司 Dosage forms, devices and methods of treatment
US20100015196A1 (en) * 2008-07-16 2010-01-21 Warsaw Orthopedic, Inc. Drug Depot Implantable Within a Joint
CN102188756A (en) * 2011-05-12 2011-09-21 天津市海河医院 Preparation method of medicated slow-release degradable bone scaffold
CN111329624A (en) * 2020-04-27 2020-06-26 滨州医学院烟台附属医院 Local automatic continuous administration supporting rod for femoral head necrosis

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1571663A (en) * 2001-10-19 2005-01-26 伊莱利利公司 Dosage forms, devices and methods of treatment
US20100015196A1 (en) * 2008-07-16 2010-01-21 Warsaw Orthopedic, Inc. Drug Depot Implantable Within a Joint
CN102188756A (en) * 2011-05-12 2011-09-21 天津市海河医院 Preparation method of medicated slow-release degradable bone scaffold
CN111329624A (en) * 2020-04-27 2020-06-26 滨州医学院烟台附属医院 Local automatic continuous administration supporting rod for femoral head necrosis

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