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CN109045368A - A kind of medical high-strength degree high tenacity absorbable composite biomaterial - Google Patents

A kind of medical high-strength degree high tenacity absorbable composite biomaterial Download PDF

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Publication number
CN109045368A
CN109045368A CN201810726129.9A CN201810726129A CN109045368A CN 109045368 A CN109045368 A CN 109045368A CN 201810726129 A CN201810726129 A CN 201810726129A CN 109045368 A CN109045368 A CN 109045368A
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composite biomaterial
medical
strength
toughness
absorbable composite
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Pending
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CN201810726129.9A
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Chinese (zh)
Inventor
贾占奎
杨锦建
李松超
姚文诚
孙科
丁亚飞
金志波
郝钢
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First Affiliated Hospital of Zhengzhou University
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First Affiliated Hospital of Zhengzhou University
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Priority to CN201810726129.9A priority Critical patent/CN109045368A/en
Publication of CN109045368A publication Critical patent/CN109045368A/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
    • A61L31/04Macromolecular 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
    • A61L31/02Inorganic materials
    • A61L31/022Metals or alloys
    • 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
    • A61L31/02Inorganic materials
    • A61L31/028Other inorganic materials not covered by A61L31/022 - A61L31/026
    • 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
    • A61L31/042Polysaccharides
    • 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
    • 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
    • A61L31/148Materials at least partially resorbable by the body
    • 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
    • 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
    • A61L2300/102Metals or metal compounds, e.g. salts such as bicarbonates, carbonates, oxides, zeolites, silicates
    • A61L2300/104Silver, e.g. silver sulfadiazine
    • 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

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

Abstract

The present invention provides a kind of medical high-strength degree high tenacity absorbable composite biomaterial, chemical component contains by mass percentage: nanometer β-Ca3(PO4)210%~15%, chitosan 6%~12%, nano-silver thread 2.5%~4.0%, surplus are polylactic acid;Preparation process of the present invention are as follows: through heat-die compaction at the processing temperature of hot moulding is 75~250 DEG C, and the pressure of hot moulding is 2~10MPa after mixing raw material;Composite biological material prepared by the present invention has the characteristics that intensity height, good toughness, antibacterial, good biocompatibility, has self-bone grafting and osteoacusis active, can be made into various orthopedic fixer tools.

Description

A kind of medical high-strength degree high tenacity absorbable composite biomaterial
Technical field
The invention belongs to medical new material technology field, in particular to a kind of medical high-strength degree high tenacity can absorb compound life Object material.
Background technique
Bone fixation means are the implantation intracorporal medical devices of people, are the treatment indispensable medical instrument of orthopaedic disease, mesh There are three types of preceding common internal fixation device part implantation materials: metal material, inorganic non-metallic and molecular absorbable material.Gold Belong to material there is needing to carry out higher second operation taking-up, elasticity modulus, stress-shielding effect, internal foreign matter, nothing Machine is nonmetallic and molecular absorbable material becomes current internal fixation device part widely used biomaterial in implantation material.
Tricalcium phosphate [Ca3(PO4)2] there is chemical composition similar with inorganic phase in bone, it is that most common biology is compound The filler of material, Chinese patent (CN1403167) and United States Patent (USP) (US5981619) once disclose tricalcium phosphate polymer are added In obtain the preferable Biocomposite material of mechanical property.Tricalcium phosphate can be special in implantation interfacial initiation as bone renovating material Biologically, chemical bonding can be formed between material and osseous tissue interface, induce the reparation and regeneration of bone.
Polylactic acid (PLLA) is a kind of novel biodegradable material, have good mechanical property, biocompatibility, It is degradable and be absorbed, but polylactic acid inactive, and its acid degradation products can cause internal inflammatory reaction, cause office The damage of portion's tissue.
Chitosan (CS) is that the chitin (chitin) being widely present by nature is obtained by deacetylation, chemistry Entitled Chitosan (1-4) -2- amino-B-D glucose, biological functionality and compatibility, the blood of this natural polymer The excellent performances such as liquid phase capacitive, safety, microbic resolvability are by pharmaceuticals industry extensive concern;Chitosan is a kind of degradable Natural biological polysaccharide has the effects that promote blood coagulation and wound healing;Chitosan and human-body biological compatibility are good, but lack bone Conduction and bone-inducting active;But chitosan exclusive use mechanical property is undesirable, especially in vivo under wet condition due to inhaling Aqueous to cause very much mechanical strength loss by force quickly, catabolite is Glucosamine, is in alkalescent.
But no matter which kind of inorganic non-metallic material or molecular absorbable material all exist tenacity it is low, can not be with metal The deficiency that material is mentioned in the same breath.
Domestic number of patent application is 201210255385.7 to disclose a kind of absorbable composite biomaterial and its preparation side Method, application No. is 201210524447.X to disclose a kind of absorbable bone screw and its preparation method and application, by both skills The bone anchor of art preparation deposits intensity in use and the low problem of toughness, and part thereof does not fully recover in patient When occur as soon as the accidents such as fracture, abrasion.
Summary of the invention
To solve the above-mentioned problems, the invention reside in by nanometer-Ca3(PO4)2, polylactic acid, chitosan, nano-silver thread phase In conjunction with, a kind of medical high-strength degree high tenacity absorbable composite biomaterial is provided, have intensity height, good toughness, antibacterial, biofacies Capacitive is good, have the characteristics that self-bone grafting and osteoacusis is active.
Based on object above, the present invention provides a kind of medical high-strength degree high tenacity absorbable composite biomaterials, special Sign is, described its chemical component of medical high-strength degree high tenacity absorbable composite biomaterial is by mass percentage are as follows: receives Rice β-Ca3(PO4)210%~15%, chitosan 6%~12%, nano-silver thread 2.5%~4.0%, surplus are polylactic acid.
Nanometer β-the Ca3(PO4)2Partial size be 40~100nm, be in nano-scale particle.
The partial size of the chitosan is 80~320 μm.
The polylactic acid is average molecular weight 1 × 105~7 × 105L-lactic acid.
The diameter of the nano-silver thread is 50~100nm.
Further, a kind of medical high-strength degree high tenacity absorbable composite biomaterial is made by following steps:
By the nanometer β-Ca of formula ratio3(PO4)2, chitosan, nano-silver thread, polylactic acid mixed, then through hot moulding It is made;The processing temperature of hot moulding is 75~250 DEG C, and the pressure of hot moulding is 2~10MPa.
Innovative characteristics of the invention are as follows: metal material, inorganic non-metallic material, organic material are combined, prepare one Kind medical high-strength degree high tenacity absorbable composite biomaterial has intensity height, good toughness, antibacterial, good biocompatibility, has The features such as self-bone grafting and active osteoacusis, can be made into various orthopedic fixer tools.
Nano-silver thread in the present invention not only has antibacterial action, also largely enhances the intensity of material and tough Property;Nano beta-Ca3(PO4)2With good bioactivity and degradability, a large amount of phosphoric acid for being released in degradation process The deposition of osteoid apatite mineral can be formed in situ in radical ion and calcium ion, is conducive in internal orthopedic fixer tool degradation process The regeneration of bone tissue;The porous structure formed after chitosan fast degradation is conducive to growing into for bone tissue, the weak base of degradation product Property can neutralize the acidity of polylactic acid degradation product.
Detailed description of the invention
Fig. 1 is medical high-strength degree high tenacity absorbable composite biomaterial SEM prepared by the embodiment of the present invention 3.
Specific embodiment
Principles and features of the present invention are described with reference to embodiments, listed give an actual example is served only for explaining this hair It is bright, not limit the scope of the invention.
Embodiment 1:
1) ingredient: by mass percentage are as follows: the nanometer β-Ca of partial size 40nm3(PO4)210%, 150 μm of partial size of shell is poly- The nano-silver thread 3.0% of sugar 12%, diameter 60nm, surplus are molecular weight 5 × 105L-lactic acid;
2) raw material prepared being placed in mold, is heated to 150 DEG C of progress hot mouldings, the pressure of hot moulding is 5MPa, Pressure maintaining 30min;
3) Mechanics Performance Testing;
4) 50mm × 50mm × 10mm test piece antibacterial experiment: is made through anhydrous second in the composite biological material prepared Alcohol, deionized water ultrasonic cleaning, each 8min are then placed in 75% alcoholic solution of volume fraction and sterilize 45min.Testing bacterium is Staphylococcus aureus.The test plate (panel) after disinfection is put into culture dish first, addition 50mL bacteria suspension, static gas wave refrigerator 2h, so that Bacterium is sufficiently sticked;The bacterium that surface porosity is sticked is rinsed out with PBS solution later, is rinsed 3 times altogether;Answering after will be flushed It closes biomaterial test plate (panel) to put into 50mLPBS solution, sonic oscillation 3min rinses out the bacterium of surface adhesion.It will contain later There is the PBS solution of surface adhesion bacterium to take 5mL, be uniformly layered on plate, plate is put into 37 DEG C of constant temperature incubation 12h is cultivated in case, observation calculates clump count.
5) bone-inducting active is tested: 100mm × 100mm × 5mm test piece is made in the composite biological material prepared, Neonate rat Calvarial osteoblast is inoculated in test piece, inoculum density is 300/mm2, with the new life for being 10% containing volume fraction The DMEM culture medium culture of cow's serum, every 1d change liquid, cultivate 3d and 5d respectively, and then MTT 0.1mL, 37 DEG C of cultures are added in every hole 4h inhales and abandons supernatant, then DMSO 0.5mL is added in every hole, and absorbance is measured at wavelength 490nm with microplate reader.
Embodiment 2:
1) ingredient: by mass percentage are as follows: the nanometer β-Ca of partial size 80nm3(PO4)212%, 300 μm of partial size of shell is poly- The nano-silver thread 4.0% of sugar 9%, diameter 100nm, surplus are molecular weight 6 × 105L-lactic acid;
2) raw material prepared being placed in mold, is heated to 190 DEG C of progress hot mouldings, the pressure of hot moulding is 8MPa, Pressure maintaining 30min;
3) Mechanics Performance Testing;
4) it antibacterial experiment: is carried out by embodiment 1;
5) bone-inducting active is tested: being carried out by embodiment 1.
Embodiment 3:
1) ingredient: by mass percentage are as follows: the nanometer β-Ca of partial size 100nm3(PO4)215%, 200 μm of partial size of shell The nano-silver thread 3.5% of glycan 10%, diameter 75nm, surplus are molecular weight 5 × 105L-lactic acid;
2) raw material prepared being placed in mold, is heated to 205 DEG C of progress hot mouldings, the pressure of hot moulding is 10MPa, Pressure maintaining 30min;
3) Mechanics Performance Testing;
4) it antibacterial experiment: is carried out by embodiment 1;
5) bone-inducting active is tested: being carried out by embodiment 1.
Comparative example 1:
1) ingredient: by mass percentage are as follows: the nanometer β-Ca of partial size 100nm3(PO4)215%, 200 μm of partial size of shell Glycan 10%, surplus are molecular weight 5 × 105L-lactic acid;
2) raw material prepared being placed in mold, is heated to 205 DEG C of progress hot mouldings, the pressure of hot moulding is 10MPa, Pressure maintaining 30min;
3) Mechanics Performance Testing;
4) it antibacterial experiment: is carried out by embodiment 1;
5) bone-inducting active is tested: being carried out by embodiment 1.
Comparative example 2:
1) ingredient: by mass percentage are as follows: the nano-silver thread of the chitosan 10%, diameter 75nm that 200 μm of partial size 3.5%, surplus is molecular weight 5 × 105L-lactic acid;
2) raw material prepared being placed in mold, is heated to 205 DEG C of progress hot mouldings, the pressure of hot moulding is 10MPa, Pressure maintaining 30min;
3) Mechanics Performance Testing;
4) it antibacterial experiment: is carried out by embodiment 1;
5) bone-inducting active is tested: being carried out by embodiment 1.
Embodiment and comparative example obtains that the results are shown in Table 1.
Table 1
Examples detailed above shows: composite biological material intensity height prepared by the present invention, has antibiotic property and self-bone grafting at good toughness Active (embodiment 1,2,3);Be not added with nano-silver thread composite biological material intensity and poor toughness, without antibiotic property (comparative example 1); It is not added with a nanometer β-Ca3(PO4)2Composite biological material bone-inducting active it is poor (comparative example 2).
The above embodiments merely illustrate the technical concept and features of the present invention, and its object is to allow person skilled in the art Scholar cans understand the content of the present invention and implement it accordingly, and it is not intended to limit the scope of the present invention.It is all according to the present invention Equivalent change or modification made by Spirit Essence, should be covered by the protection scope of the present invention.

Claims (7)

1.一种医用高强度高韧性可吸收复合生物材料,其特征在于,其化学成分按质量百分比计为:纳米β-Ca3(PO4)2 10%~15%、壳聚糖6%~12%、纳米银线2.5%~4.0%,余量为聚乳酸。1. A medical high-strength high-toughness absorbable composite biomaterial is characterized in that its chemical composition is calculated by mass percentage: nanometer β-Ca 3 (PO 4 ) 2 10%~15%, chitosan 6%~ 12%, nano-silver wire 2.5%-4.0%, and the balance polylactic acid. 2.根据权利要求1所述的医用高强度高韧性可吸收复合生物材料,其特征在于,将配方量的纳米β-Ca3(PO4)2、壳聚糖、纳米银线、聚乳酸进行混合,然后经热模压制成形。2. The medical high-strength and high-toughness absorbable composite biomaterial according to claim 1 is characterized in that, the nano-β-Ca 3 (PO 4 ) 2 , chitosan, nano-silver wire, and polylactic acid Mixed and then pressed into shape by hot molding. 3.根据权利要求1所述的医用高强度高韧性可吸收复合生物材料,其特征在于,所述的纳米β-Ca3(PO4)2的粒径为40~100nm。3. The medical high-strength and high-toughness absorbable composite biomaterial according to claim 1, characterized in that the particle size of the nanometer β-Ca 3 (PO 4 ) 2 is 40-100 nm. 4.根据权利要求1所述的医用高强度高韧性可吸收复合生物材料,其特征在于,所述的壳聚糖的粒径为80~320μm。4. The medical high-strength and high-toughness absorbable composite biomaterial according to claim 1, characterized in that the particle size of the chitosan is 80-320 μm. 5.根据权利要求1所述的医用高强度高韧性可吸收复合生物材料,其特征在于,所述的纳米银线的直径为50~100nm。5. The medical high-strength and high-toughness absorbable composite biomaterial according to claim 1, characterized in that the diameter of the silver nanowires is 50-100 nm. 6.根据权利要求1所述的医用高强度高韧性可吸收复合生物材料,其特征在于,所述的聚乳酸为平均分子量在1×105~7×105的左旋聚乳酸。6. The medical high-strength and high-toughness absorbable composite biomaterial according to claim 1, characterized in that the polylactic acid is L-polylactic acid with an average molecular weight of 1×10 5 -7×10 5 . 7.根据权利要求1和2所述的医用高强度高韧性可吸收复合生物材料,其特征在于,热模压的加工温度为75~250℃,热模压的压力为2~10MPa。7. The medical high-strength and high-toughness absorbable composite biomaterial according to claims 1 and 2, characterized in that the processing temperature of hot molding is 75-250° C., and the pressure of hot molding is 2-10 MPa.
CN201810726129.9A 2018-07-04 2018-07-04 A kind of medical high-strength degree high tenacity absorbable composite biomaterial Pending CN109045368A (en)

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