CN104740692B - Fixation implant and preparation method thereof in a kind of bone - Google Patents

Fixation implant and preparation method thereof in a kind of bone Download PDF

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Publication number
CN104740692B
CN104740692B CN201310751790.2A CN201310751790A CN104740692B CN 104740692 B CN104740692 B CN 104740692B CN 201310751790 A CN201310751790 A CN 201310751790A CN 104740692 B CN104740692 B CN 104740692B
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China
Prior art keywords
bone
fixation implant
layer
medicine
matrix
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Expired - Fee Related
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CN201310751790.2A
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Chinese (zh)
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CN104740692A (en
Inventor
耿芳
张隽
潘礼存
林忠
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SUHZOU HEALTH MEDICAL TREATMENT APPARATUS CO Ltd
Shanghai Microport Orthopedics Co Ltd
Original Assignee
SUHZOU HEALTH MEDICAL TREATMENT APPARATUS CO Ltd
Shanghai Microport Orthopedics Co Ltd
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Application filed by SUHZOU HEALTH MEDICAL TREATMENT APPARATUS CO Ltd, Shanghai Microport Orthopedics Co Ltd filed Critical SUHZOU HEALTH MEDICAL TREATMENT APPARATUS CO Ltd
Priority to CN201310751790.2A priority Critical patent/CN104740692B/en
Priority to PCT/CN2014/090076 priority patent/WO2015101099A1/en
Publication of CN104740692A publication Critical patent/CN104740692A/en
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Publication of CN104740692B publication Critical patent/CN104740692B/en
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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
    • A61L31/00Materials 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
    • A61L31/14Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L31/16Biologically active materials, e.g. therapeutic substances
    • 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
    • A61L31/00Materials 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
    • A61L31/04Macromolecular materials
    • A61L31/06Macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
    • 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
    • A61L31/00Materials 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
    • A61L31/08Materials for coatings
    • A61L31/10Macromolecular materials
    • 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
    • A61L2300/406Antibiotics
    • 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
    • A61L2420/00Materials or methods for coatings medical devices
    • A61L2420/08Coatings comprising two or more layers

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Surgery (AREA)
  • Vascular Medicine (AREA)
  • Epidemiology (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Medicinal Chemistry (AREA)
  • Molecular Biology (AREA)
  • Materials For Medical Uses (AREA)
  • Medicinal Preparation (AREA)

Abstract

The present invention relates to medical instruments field.Specifically, the present invention relates to fixation implant in a kind of bone and preparation method thereof.The Fracture internal fixaiion implant is using Biodegradable polymer material as matrix, and matrix surface is loaded with medication coat, and the medication coat is double-decker, is slow releasing medicinal nitride layer close to the first layer of matrix, is quick-release hydrophilic layer in the second layer of first layer appearance.Fixation implant has antibacterial, absorbable, fixed triple functions in the bone of the present invention.

Description

Fixation implant and preparation method thereof in a kind of bone
Technical field
The invention belongs to medical instruments field.Specifically, the present invention relates to fixation implant and its preparation in a kind of bone Method.
Background technology
Fixation implant is typically made up of the higher metal alloy of rigidity and intensity in traditional bone, and such as stainless steel, titanium are closed Gold etc..Metal has good biocompatibility and high intensity and anti-fatigue performance.But these common metal non-degradables are inhaled Receive, fix in synthetism, be drawn off, it is necessary to carry out second operation after union.Meanwhile, also there is Elastic Modulus for Metals far high In the modulus of elasticity of bone, the normal stress environment of skeleton healing can be destroyed, stress-shielding effect occurs, not only hindering bone The quick formation of folding part position poroma, also results in the complication such as osteoporosis, refracture can be also caused when serious.In addition, implantation Metallic weapon can influence patient to carry out the inspection such as CT or MRI, so as to influence surgical quality.
Resorbable polymeric materials such as PGA, PLA, polycaprolactone etc., due to good biocompatibility And degradability and be widely used.Load position can not rise bone inner fixing member prepared by such high polymer material in skeleton To the effect of traditional bone inner fixing member, and with the healing of fracture, fixation implant is degradable in such bone is absorbed by the body, Taken out without second operation.Moreover, modulus of elasticity is closer to skeleton modulus of elasticity, be conducive to union, also will not shadow Ring patient and carry out the inspection such as CT or MRI.In addition, resorbable polymeric materials have very powerful plasticity, allow its root According to different use position random-shapings and it is repeatable it is moulding use, and it is moulding after can be fitted with required position " seamless ".
However, either metal or high molecular degradable material, orthopaedics implant surgery is postoperative all exist it is a certain proportion of Cases of infection, the incidence of disease especially for such as open fracture bacterium infection is it is reported that up to 30%.And for treatment implantation phase It is also very challenging process while being one expensive, lasting for the infection of pass.Most common treatment method All implants are taken out including long-term antibiotic medication and second operation.Certainly, it is right in actual clinical application In prevention infection generally by the way of systemic drug intake, but because postoperative surgical region blood transports not good, it is difficult in respective area Domain forms effective germ killing drugs concentration.Therefore, local bacteriostatic slow-released system is paid attention to.Topical remedy's slow-released system can be in short-term Interior reach bacteriocidal concentration hundreds and thousands of times, and finite concentration is maintained to the predetermined time.In open wound operation, because of sense Contaminate in the bone surgery that the second operation caused, patients with multiple injuries operation, patient of the resistance that has a delicate constitution difference etc. easily infect Application prospect is huge.
As can be seen here, fixation implant has two key issues in bone, and one is material, and the use of absorbable material is bone The development trend of section's implant;Another is the infection problems of implant.After fixation implant implants in orthopaedics, occur There is certain ratio in the possibility of infection, fixation implant surgical infection rate is up to 30% in especially open bone.
The content of the invention
In order to solve the above problems, the present invention provides fixation implant in a kind of novel antibacterial bone.It is fixed in absorbable to plant Enter thing surface and prepare antibacterials coating, realize fixed and antibacterial dual-use function.Antimicrobial coating is bilayer, can effectively realize early stage Quick release simultaneously can keep long-term sustained release effect of drugs.
The present invention provides fixation implant in a kind of bone, and it is using Biodegradable polymer material as matrix, matrix surface It is loaded with medication coat.
According to the present invention, medication coat is double-decker, is slow releasing medicinal nitride layer close to the first layer (bottom) of matrix, to protect Hold long-term sustained release effect of drugs;It is quick-release hydrophilic layer in the second layer (top layer) of first layer appearance, effectively to realize that early stage is quick Release.
According to the present invention, the material of matrix includes the absorbable matrix material commonly used in orthopaedics implant, particularly can The high polymer material of degraded, preferably PGA, PLA and/or polycaprolactone etc..
According to the present invention, slow releasing medicinal nitride layer includes pharmaceutical carrier and medicine, and the mass ratio of preferred agents carrier and medicine is 10:1-1:1, including any numerical point in the range of this.
According to the present invention, pharmaceutical carrier includes the degradable macromolecule material that sustained release purpose can be achieved known to field of medicaments Material, degradable polylactic acid-based high polymer material, preferably PLA, poly lactic-co-glycolic acid particularly known to field of medicaments Copolymer etc., more preferably PLA, particularly preferred weight average molecular weight are 20,000-30,000 PLA, the Weight-average molecular Measuring scope includes any numerical point in the range of this.
According to the present invention, medicine is antibacterials, and preferred antibiotics, specifically aminoglycoside antibiotics are for example celebrated big Mycin, TOB etc.;Or polypeptide antibiotics, such as vancomycin;Or fluoquinolone antibiotics, such as Ciprofloxacin Deng;And any one or more of the medicine are combined.The medicine is selected according to different indications.
According to the present invention, quick-release hydrophilic layer includes the quality of hydrophilic carrier and medicine, preferred hydrophilic carrier and medicine Than for 1:10-3:1, including any numerical point in the range of this.
According to the present invention, hydrophilic carrier is selected from the hydrophily load that quick release purpose can be achieved known to field of medicaments Body, such as gelatin, hyaluronic acid or chitosan, preferably clear matter acid.
According to the present invention, the drugloading rate of slow releasing medicinal nitride layer is 1.0-3.0mg/cm2.Can be according to coating structure difference adjustment institute Drugloading rate is stated, in 1-6 months adjacent tissue can be kept to produce the purpose more than medicine MIC concentration to reach.
According to the present invention, the thickness of slow releasing medicinal nitride layer is 10-50 μm.The thickness of the slow releasing medicinal nitride layer can be by this area skill Art personnel are adjusted as needed.
According to the present invention, the drugloading rate of hydrophilic coating is 1.0-6.0mg/cm2.Can be according to coating structure difference adjustment institute Drugloading rate is stated, to reach that burst size reaches minimal inhibitory concentration in 1-3 days(MIC)Hundred times of the above object.
According to the present invention, the thickness of hydrophilic coating is 5-30 μm.The thickness of the hydrophilic coating can be by this area skill Art personnel are adjusted as needed.
The present invention also provides a kind of preparation method of fixation implant in bone, comprises the following steps:
1)High-strength, high-ductility, absorbable, the sheet material of Biodegradable high-molecular, bar etc. are prepared using mould pressing technology, then It is machined to matrix (including plate, nail, rod and other types);Or matrix is prepared using injection molding technology;
2)Prepare drug containing and pharmaceutical carrier (antibiotic with degradable high polymer material, gelatin, hyaluronic acid etc. mix) Mixed solution;
3)Using spray applicator, the mixed solution is sprayed in matrix surface, or use dipping process by the base Body is immersed in mixed solution.
According to the present invention, include first layer in absorbable interior fixation implant matrix surface spraying carried with antibiotics coating and spray With second layer spraying.
According to the present invention, first layer spraying is that the spray coating liquor formed after pharmaceutical carrier is mixed with medicine sprays to matrix table On face, including atomizing pressure 10-12.5psi, spray time 20-50s, interval time 3-5min, spraying number of times 10-25 times.
According to the present invention, second layer spraying is that the spray coating liquor formed after hydrophilic carrier is mixed with medicine sprays to bottom On.
According to the present invention, dip-coating is similar with spraying, and the wherein dip-coating residence time is 1-3S, and dip-coating speed is 0.5-50mm/ Min, dip-coating number of times is 1-5 times, and interval time is 3-30min.
According to the present invention, after spraying or dip-coating are fully completed, dried under vacuum drying chamber, until sample constant weight.
Because pharmaceutical carrier and matrix material performance are approached, anchoring strength of coating is high.Drug release period can be according to coating Structure difference adjustment, at 1-3 days, interior burst size reached more than hundred times of minimal inhibitory concentration (MIC), effectively realized that initial stage is a large amount of The killing action of bacterium, especially for the removal of bacterial biof iotalm, and can keep adjacent tissue generation to exceed in 1-6 months Medicine MIC concentration, keeps permanently effective antibacterial action.Also different releases can be prepared by adjusting coated carrier and medicament contg Speed antimicrobial product, and select different product type, including hone lamella, nail, rod etc. according to different indications.
Fixation implant has antibacterial, absorbable, fixed triple functions in the bone of the present invention.In absorbable interior fixed implantation Thing surface prepares antibacterials coating, and antimicrobial coating is bilayer, and bond strength is high, can effectively realize early stage quick release and can protect Hold long-term sustained release effect of drugs.Antimicrobial coating can discharge tissue of the antibacterials near implant, and local concentration can reach most Effectively being sterilized into hundred to thousands of times for small Mlc, eliminates infection, and control again does not influence fracture to be cured in the range of toxic reaction Close.
Brief description of the drawings
Fig. 1 is antibacterial absorbable-bone plate design sketch.
Fig. 2 shows antibacterial effect contrast of the absorbable-bone plate before and after coating.
Fig. 3 is sample coatings structural representation.
Embodiment
For a further understanding of the present invention, the preferred scheme of the present invention is described below in conjunction with embodiment.These Description is merely illustrative the feature and advantage of fixation implant and preparation method thereof in bone of the present invention, is not intended to limit the present invention Protection domain.
Embodiment 1
Absorbable bar is prepared using mould pressing technology, nail is then machined to.Prepare Poly(D,L-lactide-co-glycolide (PLGA)With the mixed solution of vancomycin(PLGA and vancomycin ratio are 10:1), it is fitted into spray test machine spraying batch can Spray on the hone lamella that preceding working procedure is prepared, atomizing pressure 11psi, spray time 40s, interval time 5min, spray number of times 12 times.The second layer(Top layer)It is to prepare quick release hydrophilic layer, carrier uses hyaluronic acid, is equipped with the hyalomitome that concentration is 0.1% Aqueous acid, medicine is 1 with hyaluronic acid mass ratio:10, spray atomizing pressure 11psi, spray time 30s, interval time 4min, spraying number of times 10 times.Dried after the completion of spraying under vacuum drying chamber, to sample constant weight.
Embodiment 2
Absorbable sheet material is prepared using mould pressing technology, small-sized four hole hone lamella is then machined to(As shown in Figure 2).Prepare poly- The mixed solution of lactic acid and gentamicin(PLA and gentamicin ratio are 2:1), it is fitted into spray test machine spraying batch can Spray on the hone lamella that preceding working procedure is prepared, atomizing pressure 10psi, spray time 20s, interval time 3min, spray number of times 10 times.The second layer(Top layer)It is to prepare quick release hydrophilic layer, carrier uses hyaluronic acid, is equipped with the hyalomitome that concentration is 0.1% Aqueous acid, medicine is 1 with hyaluronic acid mass ratio:10, spray atomizing pressure 11psi, spray time 30s, interval time 4min, spraying number of times 15 times.Dried 3 days under vacuum drying chamber after the completion of spraying, to sample constant weight.
Embodiment 3
Bioabsorbable interference screw is prepared using injection molding technology, the mixed solution of PLA and TOB is then prepared(PLA It is 3 with TOB ratio:1), it is fitted into spray test machine spraying batch can and sprays on the nail that preceding working procedure is prepared, mist Change pressure 12psi, spray time 20s, interval time 5min, spraying number of times 15 times.The second layer(Top layer)It is to prepare quick release Hydrophilic layer, carrier uses gelatin, is equipped with the aqueous gelatin solution that concentration is 0.15%, and medicine is 1 with gelatin mass ratio:10, use Dipping process, the dip-coating residence time is 3s, and dip-coating speed is 20mm/min, and dip-coating number of times is 3 times, and interval time is 30min, leaching Dried 3 days under vacuum drying chamber after the completion of painting, to sample constant weight.
Effect example
The absorbable-bone plate of the present invention, its surface tool antimicrobial coating, can effectively discharge medicine and realize antibacterial functions.
Fig. 1 is antibacterial absorbable-bone plate design sketch.
Antibacterial effect compares figures of the Fig. 2 for absorbable-bone plate of the invention before and after coating, uses staphylococcus aureus Carry out antibacterial experiment.Test result indicates that, absorbable-bone plate prepares antibacterial effect after drug-carried coat and substantially, greatly antibacterial occurs Circle, and do not carry and overgrow with staphylococcus aureus around medicine hone lamella.
The explanation of above example is only intended to the core concept for helping to understand the present invention.It should be pointed out that for this area Those of ordinary skill for, under the premise without departing from the principles of the invention, can also to the present invention bone in fixation implant And preparation method thereof carry out some improvement and modification, but these improve and modification to also fall into the claims in the present invention claimed In the range of.

Claims (18)

1. fixation implant in a kind of bone, it is characterised in that using Biodegradable polymer material as matrix, matrix surface is loaded with Medication coat, medication coat is double-decker, and the first layer close to matrix is slow releasing medicinal nitride layer, in the second layer of first layer appearance For quick-release hydrophilic layer, the quick-release hydrophilic layer includes hydrophilic carrier.
2. fixation implant in bone as claimed in claim 1, it is characterised in that the material of matrix is degradable macromolecule material Material.
3. fixation implant in bone as claimed in claim 2, it is characterised in that degradable high polymer material is PGA, gathered Lactic acid and/or polycaprolactone.
4. fixation implant in bone as claimed in claim 1, it is characterised in that slow releasing medicinal nitride layer includes pharmaceutical carrier and medicine The quality of thing, wherein pharmaceutical carrier and medicine is 10 than scope:1-1:1.
5. fixation implant in bone as claimed in claim 4, it is characterised in that pharmaceutical carrier is PLA, PGA, gathered The degradable high polymer material of lactic acid and/or polycaprolactone.
6. fixation implant in bone as claimed in claim 5, it is characterised in that pharmaceutical carrier is PLA.
7. fixation implant in bone as claimed in claim 6, it is characterised in that the weight average molecular weight range of PLA is 20, 000-30,000。
8. fixation implant in the bone as any one of claim 4-7, it is characterised in that medicine is antibiotic.
9. fixation implant in bone as claimed in claim 8, it is characterised in that medicine is aminoglycoside antibiotics, is such as celebrated Big mycin, TOB etc.;Or polypeptide antibiotics, such as vancomycin;Or fluoquinolone antibiotics, such as sand of ring third Star, or it is any one or more compound.
10. fixation implant in bone as claimed in claim 1, it is characterised in that quick-release hydrophilic layer also includes medicine, wherein parent The quality of aqueous carrier and medicine is 1 than scope:10-3:1.
11. fixation implant in bone as claimed in claim 1, it is characterised in that hydrophilic carrier is selected from gelatin, hyaluronic acid Or chitosan.
12. fixation implant in bone as claimed in claim 11, it is characterised in that hydrophilic carrier is hyaluronic acid.
13. fixation implant in bone as claimed in claim 1, it is characterised in that the drugloading rate of slow releasing medicinal nitride layer is 1.0- 3.0mg/cm2
14. fixation implant in bone as claimed in claim 1, it is characterised in that the thickness of slow releasing medicinal nitride layer is 10-50 μm.
15. fixation implant in bone as claimed in claim 1, it is characterised in that the drugloading rate of hydrophilic layer is 1.0- 6.0mg/cm2
16. fixation implant in bone as claimed in claim 1, it is characterised in that the thickness of hydrophilic layer is 5-30 μm.
17. the preparation method of fixation implant in a kind of bone as claimed in claim 1, it is characterised in that preparation method includes The following steps:
1) sheet material of Biodegradable high-molecular, bar are prepared using mould pressing technology, is then machined to described matrix;Or use Injection molding technology prepares described matrix;
2) mixed solution of drug containing carrier and medicine is prepared;
3) spray applicator is used, in mixed solution described in described matrix surface spraying, or dipping process is used by the base Body is immersed in mixed solution.
18. preparation method as claimed in claim 17, it is characterised in that the atomizing pressure 10-12.5psi of spraying, during spraying Between 20-50s, interval time 3-5min, spraying number of times 10-25 times;The dip-coating residence time is 1-3S, and dip-coating speed is 0.5- 50mm/min, dip-coating number of times is 1-5 times, and interval time is 3-30min.
CN201310751790.2A 2013-12-31 2013-12-31 Fixation implant and preparation method thereof in a kind of bone Expired - Fee Related CN104740692B (en)

Priority Applications (2)

Application Number Priority Date Filing Date Title
CN201310751790.2A CN104740692B (en) 2013-12-31 2013-12-31 Fixation implant and preparation method thereof in a kind of bone
PCT/CN2014/090076 WO2015101099A1 (en) 2013-12-31 2014-10-31 Intraosseous fixation implant and preparation method therefor

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Application Number Priority Date Filing Date Title
CN201310751790.2A CN104740692B (en) 2013-12-31 2013-12-31 Fixation implant and preparation method thereof in a kind of bone

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CN104740692B true CN104740692B (en) 2017-09-05

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CN107754022A (en) * 2017-11-10 2018-03-06 辽宁垠艺生物科技股份有限公司 A kind of medication coat and preparation method thereof
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CN110151290A (en) * 2018-02-12 2019-08-23 香港科能有限公司 The implantation material of releasable medicaments and manufacture and application method
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CN113134114B (en) * 2021-04-25 2022-12-02 中国人民解放军总医院第八医学中心 Anti-infection coating capable of being constructed immediately in operation and preparation method and application thereof
CN113616855A (en) * 2021-08-05 2021-11-09 苏州大学 Medicine storage implant and preparation method thereof
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