CN116036384B - Preparation method of self-oxygen-supply antibacterial filling and fixing material - Google Patents
Preparation method of self-oxygen-supply antibacterial filling and fixing material Download PDFInfo
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- CN116036384B CN116036384B CN202310068228.3A CN202310068228A CN116036384B CN 116036384 B CN116036384 B CN 116036384B CN 202310068228 A CN202310068228 A CN 202310068228A CN 116036384 B CN116036384 B CN 116036384B
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- solution
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- hydrogen peroxide
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- 239000000463 material Substances 0.000 title claims abstract description 87
- 238000011049 filling Methods 0.000 title claims abstract description 86
- 230000000844 anti-bacterial effect Effects 0.000 title claims abstract description 29
- 238000002360 preparation method Methods 0.000 title abstract description 16
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 claims abstract description 90
- 239000000243 solution Substances 0.000 claims abstract description 85
- 238000003756 stirring Methods 0.000 claims abstract description 64
- 229920001223 polyethylene glycol Polymers 0.000 claims abstract description 39
- 239000002202 Polyethylene glycol Substances 0.000 claims abstract description 37
- GUJOJGAPFQRJSV-UHFFFAOYSA-N dialuminum;dioxosilane;oxygen(2-);hydrate Chemical compound O.[O-2].[O-2].[O-2].[Al+3].[Al+3].O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O GUJOJGAPFQRJSV-UHFFFAOYSA-N 0.000 claims abstract description 31
- 239000003814 drug Substances 0.000 claims abstract description 31
- 229910052901 montmorillonite Inorganic materials 0.000 claims abstract description 31
- 102000016938 Catalase Human genes 0.000 claims abstract description 25
- 108010053835 Catalase Proteins 0.000 claims abstract description 25
- 238000000034 method Methods 0.000 claims abstract description 19
- 239000003242 anti bacterial agent Substances 0.000 claims abstract description 15
- 229940088710 antibiotic agent Drugs 0.000 claims abstract description 15
- 208000002565 Open Fractures Diseases 0.000 claims abstract description 10
- 238000002347 injection Methods 0.000 claims abstract description 10
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- 238000001291 vacuum drying Methods 0.000 claims abstract description 10
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- 238000001914 filtration Methods 0.000 claims abstract 4
- 229940079593 drug Drugs 0.000 claims description 30
- QIGBRXMKCJKVMJ-UHFFFAOYSA-N Hydroquinone Chemical compound OC1=CC=C(O)C=C1 QIGBRXMKCJKVMJ-UHFFFAOYSA-N 0.000 claims description 22
- 238000011068 loading method Methods 0.000 claims description 21
- 229920003229 poly(methyl methacrylate) Polymers 0.000 claims description 16
- 239000004926 polymethyl methacrylate Substances 0.000 claims description 16
- 230000003115 biocidal effect Effects 0.000 claims description 13
- 238000001035 drying Methods 0.000 claims description 12
- VVQNEPGJFQJSBK-UHFFFAOYSA-N Methyl methacrylate Chemical compound COC(=O)C(C)=C VVQNEPGJFQJSBK-UHFFFAOYSA-N 0.000 claims description 11
- 239000003999 initiator Substances 0.000 claims description 11
- GYVGXEWAOAAJEU-UHFFFAOYSA-N n,n,4-trimethylaniline Chemical compound CN(C)C1=CC=C(C)C=C1 GYVGXEWAOAAJEU-UHFFFAOYSA-N 0.000 claims description 11
- 239000000843 powder Substances 0.000 claims description 11
- 239000011248 coating agent Substances 0.000 claims description 10
- 238000000576 coating method Methods 0.000 claims description 10
- MTHSVFCYNBDYFN-UHFFFAOYSA-N diethylene glycol Chemical compound OCCOCCO MTHSVFCYNBDYFN-UHFFFAOYSA-N 0.000 claims description 9
- 238000006243 chemical reaction Methods 0.000 claims description 8
- 239000000203 mixture Substances 0.000 claims description 8
- 239000007788 liquid Substances 0.000 claims description 7
- 238000002525 ultrasonication Methods 0.000 claims description 5
- 108010059993 Vancomycin Proteins 0.000 claims description 4
- 229960001572 vancomycin hydrochloride Drugs 0.000 claims description 4
- LCTORFDMHNKUSG-XTTLPDOESA-N vancomycin monohydrochloride Chemical compound Cl.O([C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC1=C2C=C3C=C1OC1=CC=C(C=C1Cl)[C@@H](O)[C@H](C(N[C@@H](CC(N)=O)C(=O)N[C@H]3C(=O)N[C@H]1C(=O)N[C@H](C(N[C@@H](C3=CC(O)=CC(O)=C3C=3C(O)=CC=C1C=3)C(O)=O)=O)[C@H](O)C1=CC=C(C(=C1)Cl)O2)=O)NC(=O)[C@@H](CC(C)C)NC)[C@H]1C[C@](C)(N)[C@H](O)[C@H](C)O1 LCTORFDMHNKUSG-XTTLPDOESA-N 0.000 claims description 4
- 239000008118 PEG 6000 Substances 0.000 claims description 3
- 229920001030 Polyethylene Glycol 4000 Polymers 0.000 claims description 3
- 229920002584 Polyethylene Glycol 6000 Polymers 0.000 claims description 3
- 229920002594 Polyethylene Glycol 8000 Polymers 0.000 claims description 3
- 229960000479 ceftriaxone sodium Drugs 0.000 claims description 3
- XMEVHPAGJVLHIG-FMZCEJRJSA-N chembl454950 Chemical compound [Cl-].C1=CC=C2[C@](O)(C)[C@H]3C[C@H]4[C@H]([NH+](C)C)C(O)=C(C(N)=O)C(=O)[C@@]4(O)C(O)=C3C(=O)C2=C1O XMEVHPAGJVLHIG-FMZCEJRJSA-N 0.000 claims description 3
- FDRNWTJTHBSPMW-GNXCPKRQSA-L disodium;(6r,7r)-7-[[(2e)-2-(2-amino-1,3-thiazol-4-yl)-2-methoxyiminoacetyl]amino]-3-[(2-methyl-6-oxido-5-oxo-1,2,4-triazin-3-yl)sulfanylmethyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound [Na+].[Na+].S([C@@H]1[C@@H](C(N1C=1C([O-])=O)=O)NC(=O)/C(=N/OC)C=2N=C(N)SC=2)CC=1CSC1=NC(=O)C([O-])=NN1C FDRNWTJTHBSPMW-GNXCPKRQSA-L 0.000 claims description 3
- CAOOISJXWZMLBN-PPHPATTJSA-N htn0d03vrz Chemical compound Cl.C([C@@H](N1C2=C(C(C(C(O)=O)=C1)=O)C=C1F)C)OC2=C1N1CCN(C)CC1 CAOOISJXWZMLBN-PPHPATTJSA-N 0.000 claims description 3
- 229960004989 tetracycline hydrochloride Drugs 0.000 claims description 3
- 208000027418 Wounds and injury Diseases 0.000 abstract description 17
- 230000006378 damage Effects 0.000 abstract description 6
- 208000015181 infectious disease Diseases 0.000 abstract description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 29
- 239000001301 oxygen Substances 0.000 description 29
- 229910052760 oxygen Inorganic materials 0.000 description 29
- 208000014674 injury Diseases 0.000 description 18
- 230000008733 trauma Effects 0.000 description 14
- 206010052428 Wound Diseases 0.000 description 12
- 238000001338 self-assembly Methods 0.000 description 10
- 230000000694 effects Effects 0.000 description 9
- 239000004005 microsphere Substances 0.000 description 9
- 239000001257 hydrogen Substances 0.000 description 5
- 229910052739 hydrogen Inorganic materials 0.000 description 5
- 210000001519 tissue Anatomy 0.000 description 4
- 230000000740 bleeding effect Effects 0.000 description 3
- 210000004027 cell Anatomy 0.000 description 3
- 239000000017 hydrogel Substances 0.000 description 3
- 239000011159 matrix material Substances 0.000 description 3
- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 description 2
- 208000035143 Bacterial infection Diseases 0.000 description 2
- 208000008960 Diabetic foot Diseases 0.000 description 2
- 229920002148 Gellan gum Polymers 0.000 description 2
- 206010028980 Neoplasm Diseases 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 208000022362 bacterial infectious disease Diseases 0.000 description 2
- 235000010418 carrageenan Nutrition 0.000 description 2
- 239000000679 carrageenan Substances 0.000 description 2
- 229920001525 carrageenan Polymers 0.000 description 2
- 229940113118 carrageenan Drugs 0.000 description 2
- 230000001413 cellular effect Effects 0.000 description 2
- 239000006185 dispersion Substances 0.000 description 2
- 235000010492 gellan gum Nutrition 0.000 description 2
- 239000000216 gellan gum Substances 0.000 description 2
- 229920002674 hyaluronan Polymers 0.000 description 2
- 229960003160 hyaluronic acid Drugs 0.000 description 2
- 239000010954 inorganic particle Substances 0.000 description 2
- 238000006213 oxygenation reaction Methods 0.000 description 2
- 150000002978 peroxides Chemical class 0.000 description 2
- 231100000572 poisoning Toxicity 0.000 description 2
- 230000000607 poisoning effect Effects 0.000 description 2
- 210000000130 stem cell Anatomy 0.000 description 2
- 238000013268 sustained release Methods 0.000 description 2
- 239000012730 sustained-release form Substances 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- UHVMMEOXYDMDKI-JKYCWFKZSA-L zinc;1-(5-cyanopyridin-2-yl)-3-[(1s,2s)-2-(6-fluoro-2-hydroxy-3-propanoylphenyl)cyclopropyl]urea;diacetate Chemical compound [Zn+2].CC([O-])=O.CC([O-])=O.CCC(=O)C1=CC=C(F)C([C@H]2[C@H](C2)NC(=O)NC=2N=CC(=CC=2)C#N)=C1O UHVMMEOXYDMDKI-JKYCWFKZSA-L 0.000 description 2
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
- 229920000936 Agarose Polymers 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- 229920001661 Chitosan Polymers 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 206010021143 Hypoxia Diseases 0.000 description 1
- 238000002266 amputation Methods 0.000 description 1
- 230000002924 anti-infective effect Effects 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000003519 biomedical and dental material Substances 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 239000001110 calcium chloride Substances 0.000 description 1
- 229910001628 calcium chloride Inorganic materials 0.000 description 1
- 235000011148 calcium chloride Nutrition 0.000 description 1
- 235000019402 calcium peroxide Nutrition 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000005429 filling process Methods 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 230000001146 hypoxic effect Effects 0.000 description 1
- 230000005847 immunogenicity Effects 0.000 description 1
- 238000012856 packing Methods 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- 235000010413 sodium alginate Nutrition 0.000 description 1
- 239000000661 sodium alginate Substances 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/02—Inorganic 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
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/04—Macromolecular materials
- A61L31/043—Proteins; Polypeptides; Degradation products thereof
- A61L31/047—Other specific proteins or polypeptides not covered by A61L31/044 - A61L31/046
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/04—Macromolecular materials
- A61L31/048—Macromolecular materials obtained by reactions only involving carbon-to-carbon unsaturated bonds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/04—Macromolecular materials
- A61L31/06—Macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L31/16—Biologically active materials, e.g. therapeutic substances
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—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
- A61L2300/406—Antibiotics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/60—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a special physical form
- A61L2300/602—Type of release, e.g. controlled, sustained, slow
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
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- Epidemiology (AREA)
- Heart & Thoracic Surgery (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Chemical & Material Sciences (AREA)
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- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Medicinal Chemistry (AREA)
- Molecular Biology (AREA)
- Inorganic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
Abstract
Description
技术领域Technical Field
本发明属于生物医用材料制备技术领域,涉及一种自供氧抗菌填充固定材料的制备方法。The invention belongs to the technical field of biomedical material preparation, and relates to a method for preparing a self-oxygen-supplying antibacterial filling and fixing material.
背景技术Background technique
当前,各种自然灾害导致的开放性创伤患者数量增加,虽然在后期治疗时得到了丰富的医疗技术支持,但在院前急救期仍然是采用传统夹板外固定为主,对于创伤内部起到固定作用效果甚微且固定效率低下,甚至导致创伤二次损伤或造成其他问题,进而加重伤情,存在一定短板,而急救恰对于创伤后期治疗尤为重要,因此,如何更好的对创伤进行院前急救,降低急救期产生副作用的概率,改善后期治疗效果,解决创伤院前急救技术所存在的问题是目前急需攻克的问题。创伤发生后,由于环境的原因容易造成创生部位细菌感染,如果不及时进行抗菌治疗会使得创伤部位发展成化脓性伤口,情况更严重者将会休克截肢,甚至细菌严重感染扩散引起死亡,所以材料需要具备抗菌效果,另外最重要的是患者在转运途中需要保证固定部位具有一定含量的氧气,避免填充固定后氧气含量缺少导致的细菌增殖能力加快以及正常细胞缺氧性死亡,所以,发展一种可以用于创伤部位内填充固定的自供氧抗菌材料成为解决上述问题的关键。At present, the number of patients with open trauma caused by various natural disasters has increased. Although they have received rich medical technology support in the later treatment, the traditional splint external fixation is still the main method in the pre-hospital emergency treatment period. The fixation effect on the inside of the trauma is very limited and the fixation efficiency is low. It may even cause secondary injury to the trauma or other problems, which will aggravate the injury. There are certain shortcomings. Emergency treatment is particularly important for the later treatment of trauma. Therefore, how to better perform pre-hospital emergency treatment on trauma, reduce the probability of side effects during the emergency treatment period, improve the effect of later treatment, and solve the problems existing in the pre-hospital emergency treatment technology for trauma is an urgent problem to be solved. After the trauma occurs, it is easy to cause bacterial infection at the site of injury due to environmental reasons. If antibacterial treatment is not carried out in time, the site of injury will develop into a purulent wound. In more serious cases, shock and amputation will occur, and even serious bacterial infection will spread and cause death. Therefore, the material needs to have an antibacterial effect. In addition, the most important thing is that the patient needs to ensure that the fixed site has a certain amount of oxygen during transportation to avoid the accelerated bacterial proliferation ability and the hypoxic death of normal cells caused by the lack of oxygen content after filling and fixation. Therefore, the development of a self-oxygenated antibacterial material that can be used for filling and fixation in the wound site has become the key to solving the above problems.
中国发明专利《一种缓释氧气微球及其制备方法、使用方法以及在治疗糖尿病足和肿瘤疾病中的应用》(申请号202210868565.6,公开日2022.10.21,公开号CN 115212183A)公开了一种缓释氧气微球及其制备方法、使用方法以及在治疗糖尿病足和肿瘤疾病中的应用,包括内核以及包裹在内核外侧的外壳,内核包含溶有CaCl2和PVP的H2O2溶液,外壳包括水凝胶以及粘附在水凝胶表面的过氧化氢酶和干细胞,所述水凝胶采用海藻酸钠、琼脂糖、透明质酸(HA)、壳聚糖、卡拉胶(CRG)、结冷胶(GG)中一种,释放氧气的性能稳定、装载量高、流失率低,可有效解决氧气在释放过程中用量难以控制的缺点,从而在缺氧微环境中缓慢释放氧气,提高干细胞的治疗效果。但是,该释氧微球虽然具有氧气释放控制效果,但是存在初始小程度突释现象,容易造成细胞氧中毒。中国发明专利《一种缓控释氧微球及其制备方法和用途》(申请号201810174515.1,公开日2018.07.24,公开号CN 108310470 A)公开了一种缓控释氧微球及其制备方法和用途,所述的缓控释氧微球为明胶为基质的微球,在微球内部包含过氧化无机物颗粒,过氧化无机物选自CaO2、MgO2、NaCO3、SrO2、BaO2、K2O2、Na2O2。公开的缓控释氧缓释材料具有大小可控、释氧时间长、释氧时间可控、突释率低、地细胞毒性、低免疫源性、制备过程相对简单、易于工业化等优点,在骨缺损修复的临床应用中具有较大的应用前景,但是该微球仍然具有短暂的药物突释现象,容易在初始供氧阶段造成细胞氧中毒。The Chinese invention patent "A sustained-release oxygen microsphere and its preparation method, use method and application in the treatment of diabetic foot and tumor diseases" (application number 202210868565.6, publication date 2022.10.21, publication number CN 115212183A) discloses a sustained-release oxygen microsphere and its preparation method, use method and application in the treatment of diabetic foot and tumor diseases, including an inner core and an outer shell wrapped around the outer side of the inner core, the inner core containing an H2O2 solution dissolved with CaCl2 and PVP, the outer shell including a hydrogel and catalase and stem cells adhered to the surface of the hydrogel, the hydrogel using one of sodium alginate, agarose, hyaluronic acid (HA), chitosan, carrageenan (CRG), and gellan gum (GG), with stable oxygen release performance, high loading capacity and low loss rate, which can effectively solve the disadvantage that the amount of oxygen used during the release process is difficult to control, thereby slowly releasing oxygen in an oxygen-deficient microenvironment and improving the therapeutic effect of stem cells. However, although the oxygen-releasing microspheres have the effect of controlling oxygen release, there is an initial small degree of burst release phenomenon, which can easily cause cellular oxygen poisoning. The Chinese invention patent "A slow-release oxygen microsphere and its preparation method and use" (application number 201810174515.1, publication date 2018.07.24, publication number CN 108310470 A) discloses a slow-release oxygen microsphere and its preparation method and use, wherein the slow-release oxygen microspheres are microspheres with gelatin as the matrix, and the microspheres contain peroxide inorganic particles, and the peroxide inorganic particles are selected from CaO2 , MgO2 , NaCO3 , SrO2 , BaO2 , K2O2 , and Na2O2 . The disclosed controlled-release oxygen material has the advantages of controllable size, long oxygen release time, controllable oxygen release time, low burst rate, low cytotoxicity, low immunogenicity, relatively simple preparation process, and easy industrialization. It has great application prospects in clinical applications of bone defect repair. However, the microspheres still have a short-term drug burst release phenomenon, which can easily cause cellular oxygen poisoning in the initial oxygen supply stage.
由于突释所带来的负面作用例如局部浓度过高,后期释放浓度不足,不能维持稳定的治疗效果,因此设计一种具有精准零级释放动力学模型的氧气释放载体为避免突释带来的副作用具有一定的意义。另外为满足良好的抗菌效果,药物理想化释放也应满足零级释放模型以避免药物突释产生的副作用。因此,基于现阶段的急救需求,亟需制备一种理想化零级释放型供氧抗菌开放性创伤内部填充固定急救材料,具有巨大的临床应用价值。Due to the negative effects of burst release, such as excessive local concentration and insufficient later release concentration, a stable therapeutic effect cannot be maintained. Therefore, it is of certain significance to design an oxygen release carrier with a precise zero-order release kinetic model to avoid the side effects caused by burst release. In addition, in order to achieve a good antibacterial effect, the idealized release of the drug should also meet the zero-order release model to avoid the side effects of the drug burst release. Therefore, based on the current emergency needs, it is urgent to prepare an idealized zero-order release oxygen supply antibacterial open wound internal filling and fixation emergency material, which has great clinical application value.
发明内容Summary of the invention
本发明的目的是提供一种自供氧抗菌填充固定材料的制备方法,解决了现有技术在创伤院前急救时,因用于创伤部位内部填充固定急救材料不理想导致的抗感染治疗、改善以及急救效果不足的问题。The purpose of the present invention is to provide a method for preparing a self-oxygenated antibacterial filling and fixing material, which solves the problem of insufficient anti-infection treatment, improvement and first aid effects caused by unsatisfactory first aid materials used for filling and fixing the inside of the trauma site during pre-hospital first aid of trauma in the prior art.
本发明所采用的技术方案是,一种自供氧抗菌填充固定材料的制备方法,按照以下步骤具体实施:The technical solution adopted by the present invention is a method for preparing a self-oxygen-supplying antibacterial filling and fixing material, which is specifically implemented according to the following steps:
步骤1,配制双氧水溶液,将药物按照5~15mg/ml质量体积百分比溶解在双氧水溶液中,简称溶液A;配制聚乙二醇溶液,简称溶液B;配制过氧化氢酶溶液,简称溶液C;Step 1, prepare a hydrogen peroxide solution, dissolve the drug in the hydrogen peroxide solution according to a mass volume percentage of 5 to 15 mg/ml, referred to as solution A; prepare a polyethylene glycol solution, referred to as solution B; prepare a catalase solution, referred to as solution C;
步骤2,首先将蒙脱土加入溶液A中,超声均匀分散后,进行过氧化氢及药物负载搅拌,搅拌结束后抽滤,真空干燥;然后将干燥后的蒙脱土重新分散于溶液B中,进行PEG包覆搅拌,搅拌结束后抽滤,真空干燥;最后将干燥后的蒙脱土重新分散于溶液C中,进行过氧化氢酶的搭载搅拌,搅拌结束后抽滤,真空干燥;重复本步骤多次,得到载双氧水/抗生素零级释放载体;Step 2, firstly, montmorillonite is added to solution A, and after ultrasonic uniform dispersion, hydrogen peroxide and drug loading and stirring are performed, after stirring, suction is filtered, and vacuum drying is performed; then, the dried montmorillonite is redispersed in solution B, PEG coating and stirring are performed, after stirring, suction is filtered, and vacuum drying is performed; finally, the dried montmorillonite is redispersed in solution C, catalase loading and stirring are performed, after stirring, suction is filtered, and vacuum drying is performed; this step is repeated multiple times to obtain a zero-order release carrier loaded with hydrogen peroxide/antibiotics;
步骤3,将PMMA粉体、引发剂BPO以及步骤2得到的载双氧水/抗生素零级释放载体混合均匀,得到填充固定材料成分D;Step 3, mixing PMMA powder, initiator BPO and the hydrogen peroxide/antibiotic zero-order release carrier obtained in step 2 evenly to obtain a filling and fixing material component D;
步骤4,将MMA、N,N-二甲基对甲苯胺、对苯二酚混合均匀,得到填充固定材料成分E;Step 4, mixing MMA, N,N-dimethyl-p-toluidine and hydroquinone evenly to obtain a filling and fixing material component E;
步骤5,将步骤3得到的填充固定材料成分D与步骤4得到的填充固定材料成分E混合,搅拌,通过注射形式对开放性骨折部位进行填充,待填充固定材料成分D与填充固定材料成分E反应结束后,即成。Step 5, mixing the filling and fixing material component D obtained in step 3 with the filling and fixing material component E obtained in step 4, stirring, and filling the open fracture site by injection. After the reaction between the filling and fixing material component D and the filling and fixing material component E is completed, the mixture is ready.
本发明的有益效果是,包括以下优点:The beneficial effects of the present invention include the following advantages:
1)以具有吸水作用的蒙脱土为基体,采用层层自组装技术将双氧水、抗生素、PEG以及过氧化氢酶负载于蒙拓土表面。首先,蒙脱土的吸水性可以保证材料在填充过程中吸收血液组织液进而膨胀,从而使PMMA材料膨胀,膨胀产生的压应力使填充更为密实并且对周围出血组织进行压迫止血,达到填充止血双重目的;其次,层层自组装技术依靠于动态氢键将所有物质进行复合,双氧水以及抗生素在依靠浓度差进行释放,双氧水在释放时经过氧化氢酶分解产生氧气,氧气的释放可以为创伤部位自供氧保证创伤部位氧气含量充足,预防多种细菌滋生,繁殖,并且能够使伤口局部保持干燥;另外,自供氧功能可以使组织细胞得到更充足的氧气,避免在固定期间细胞缺氧性死亡,同时抗生素的释放能够对创伤部位进行广谱抗菌,避免或者对创伤部位进行预防或抗菌治疗。1) Using montmorillonite with water absorption as the matrix, hydrogen peroxide, antibiotics, PEG and catalase are loaded on the surface of montmorillonite by layer-by-layer self-assembly technology. First, the water absorption of montmorillonite can ensure that the material absorbs blood tissue fluid and then expands during the filling process, so that the PMMA material expands. The compressive stress generated by the expansion makes the filling more dense and compresses the surrounding bleeding tissue to stop bleeding, achieving the dual purpose of filling and stopping bleeding; secondly, the layer-by-layer self-assembly technology relies on dynamic hydrogen bonds to compound all substances, hydrogen peroxide and antibiotics are released by concentration difference, and hydrogen peroxide is decomposed by catalase to produce oxygen when released. The release of oxygen can provide self-oxygenation for the wound site to ensure sufficient oxygen content in the wound site, prevent the growth and reproduction of various bacteria, and keep the wound local dry; in addition, the self-oxygenation function can enable tissue cells to obtain more sufficient oxygen, avoid cell anoxic death during fixation, and the release of antibiotics can perform broad-spectrum antibacterial to the wound site, avoid or prevent or treat the wound site with antibacterial treatment.
2)所制备的氧气/抗生素释放载体是基于动态氢键制备的多层自组装体,双氧水以及抗生素在释放速率与层间的氢键崩解有关,同时利用PEG分子量作为崩解速率决定开关使得氢键的崩解受控,进而控制药物的释放,同时,PEG的崩解速率恒定,最终使氧气以及抗生素是释放呈零级释放且不受其他因素影响。2) The prepared oxygen/antibiotic release carrier is a multilayer self-assembly based on dynamic hydrogen bonds. The release rate of hydrogen peroxide and antibiotics is related to the disintegration of hydrogen bonds between layers. At the same time, the molecular weight of PEG is used as a switch to determine the disintegration rate so that the disintegration of hydrogen bonds is controlled, thereby controlling the release of drugs. At the same time, the disintegration rate of PEG is constant, so that the release of oxygen and antibiotics is zero-order and is not affected by other factors.
3)采用生物相容性良好的PMMA固定材料作为基体,一方面是因为其具有良好的生物相容性,在对创伤部位进行填充期间保证人体组织的安全性,其次PMMA材料具有一定的可塑性,可以根据创伤部位任意塑形,PMMA材料具有自固化性,固化后具有高的机械性能,在充分固定后可以保护填充部位,避免因转运途中的其他原因造成二次损伤。3) PMMA fixation material with good biocompatibility is used as the matrix. On the one hand, it has good biocompatibility and ensures the safety of human tissue during the filling of the wound site. Secondly, PMMA material has a certain plasticity and can be shaped arbitrarily according to the wound site. PMMA material is self-curing and has high mechanical properties after curing. After being fully fixed, it can protect the filling site and avoid secondary damage due to other reasons during transportation.
具体实施方式Detailed ways
本发明的自供氧抗菌填充固定材料的制备方法,按照以下步骤具体实施:The preparation method of the self-oxygen-supplying antibacterial filling and fixing material of the present invention is specifically implemented according to the following steps:
步骤1,配制双氧水溶液,将药物按照5~15mg/ml质量体积百分比溶解在双氧水溶液中,简称溶液A;配制聚乙二醇(PEG)溶液,简称溶液B;配制过氧化氢酶溶液,简称溶液C;Step 1, prepare a hydrogen peroxide solution, dissolve the drug in the hydrogen peroxide solution according to a mass volume percentage of 5 to 15 mg/ml, referred to as solution A; prepare a polyethylene glycol (PEG) solution, referred to as solution B; prepare a catalase solution, referred to as solution C;
双氧水溶液的体积分数为20~40%,聚乙二醇(PEG)溶液的浓度为75~115mg/ml,过氧化氢酶溶液的浓度为100~400μg/ml;The volume fraction of the hydrogen peroxide solution is 20-40%, the concentration of the polyethylene glycol (PEG) solution is 75-115 mg/ml, and the concentration of the catalase solution is 100-400 μg/ml;
药物选用盐酸万古霉素、盐酸左氧氟沙星、盐酸四环素或头孢曲松钠中的一种;The drug selected is one of vancomycin hydrochloride, levofloxacin hydrochloride, tetracycline hydrochloride or ceftriaxone sodium;
PEG选用PEG2000、PEG4000、PEG6000、PEG8000或PEG10000中的一个。PEG is selected from among PEG2000, PEG4000, PEG6000, PEG8000 and PEG10000.
步骤2,首先将蒙脱土加入溶液A中,超声均匀分散后,进行过氧化氢及药物负载搅拌,搅拌结束后抽滤,真空干燥;然后将一次干燥后的蒙脱土重新分散于溶液B中,进行PEG包覆搅拌,搅拌结束后抽滤,真空干燥;最后将二次干燥后的蒙脱土重新分散于溶液C中,进行过氧化氢酶的搭载搅拌,搅拌结束后抽滤,真空干燥;重复本步骤多次,利用层层自组装技术得到载双氧水/抗生素零级释放载体;Step 2, firstly, montmorillonite is added to solution A, and after ultrasonic uniform dispersion, hydrogen peroxide and drug loading and stirring are performed, after stirring, suction is filtered, and vacuum drying is performed; then, the montmorillonite after primary drying is redispersed in solution B, PEG coating and stirring are performed, after stirring, suction is filtered, and vacuum drying is performed; finally, the montmorillonite after secondary drying is redispersed in solution C, catalase loading and stirring are performed, after stirring, suction is filtered, and vacuum drying is performed; this step is repeated multiple times, and a hydrogen peroxide/antibiotic zero-order release carrier is obtained by using layer-by-layer self-assembly technology;
蒙脱土的质量为溶液A体积的20~40%,过氧化氢及药物负载搅拌的时间为1~2h,PEG包覆搅拌的时间为1~2h,过氧化氢酶搭载搅拌的时间为1~2h,重复循环次数为3~8次。The mass of montmorillonite is 20-40% of the volume of solution A, the stirring time for hydrogen peroxide and drug loading is 1-2 hours, the stirring time for PEG coating is 1-2 hours, the stirring time for catalase loading is 1-2 hours, and the number of repeated cycles is 3-8 times.
步骤3,将PMMA粉体、引发剂BPO以及步骤2得到的载双氧水/抗生素零级释放载体混合均匀,得到急救用途的填充固定材料成分D;Step 3, mixing PMMA powder, initiator BPO and the hydrogen peroxide/antibiotic zero-order release carrier obtained in step 2 evenly to obtain a filling and fixing material component D for emergency use;
其中,PMMA粉体、引发剂BPO以及载双氧水/抗生素零级释放载体三者的质量比为49.95~69.85:0.05~0.15:30~50。Among them, the mass ratio of PMMA powder, initiator BPO and hydrogen peroxide/antibiotic zero-order release carrier is 49.95-69.85:0.05-0.15:30-50.
步骤4,将MMA、N,N-二甲基对甲苯胺、对苯二酚混合均匀,得到急救用途的填充固定材料成分E;Step 4, mixing MMA, N,N-dimethyl-p-toluidine and hydroquinone evenly to obtain a filling and fixing material component E for first aid use;
其中,MMA、N,N-二甲基对甲苯胺、对苯二酚三者的质量比为96.5~99.5:0.3~3:0.1~0.5。Among them, the mass ratio of MMA, N,N-dimethyl-p-toluidine and hydroquinone is 96.5-99.5:0.3-3:0.1-0.5.
步骤5,将步骤3得到的填充固定材料成分D与步骤4得到的填充固定材料成分E按照固液比为1~2g/ml混合,搅拌,通过注射形式对开放性骨折部位进行填充,待填充固定材料成分D与填充固定材料成分E反应结束后,即可对创伤部位进行进一步的固定。Step 5, mix the filling and fixing material component D obtained in step 3 and the filling and fixing material component E obtained in step 4 at a solid-liquid ratio of 1 to 2 g/ml, stir, and fill the open fracture site by injection. After the reaction between the filling and fixing material component D and the filling and fixing material component E is completed, the trauma site can be further fixed.
本发明自供氧抗菌填充固定材料的制备方法,首先采用动态氢键层层自组装技术,将双氧水、抗生素、PEG以及过氧化氢酶负载于蒙脱土上制备成零级释放载体,其次将PMMA粉体、引发剂BPO以及载双氧水/抗生素零级释放载体混合均匀,得到填充固定材料成分D,将MMA、N,N-二甲基对甲苯胺、对苯二酚混合均匀,得到填充固定材料成分E,最后将两种成分进行混合得到零级释放型供氧抗菌开放性骨折内部填充固定急救材料,注射填塞即可对开放性骨折进行充分填充,PMMA硬化后即可对填充部位进行固定。The preparation method of the self-oxygen-supplying antibacterial filling and fixing material of the present invention comprises the following steps: firstly, hydrogen peroxide, antibiotics, PEG and catalase are loaded on montmorillonite by adopting dynamic hydrogen bond layer-by-layer self-assembly technology to prepare a zero-order release carrier; secondly, PMMA powder, initiator BPO and the zero-order release carrier loaded with hydrogen peroxide/antibiotics are evenly mixed to obtain a filling and fixing material component D; MMA, N,N-dimethyl-p-toluidine and hydroquinone are evenly mixed to obtain a filling and fixing material component E; finally, the two components are mixed to obtain a zero-order release oxygen-supplying antibacterial open fracture internal filling and fixing first aid material; the open fracture can be fully filled by injection packing, and the filled part can be fixed after PMMA hardens.
实施例1Example 1
本发明自供氧抗菌填充固定材料的制备方法,具体过程为:The preparation method of the self-oxygen-supplying antibacterial filling and fixing material of the present invention comprises the following specific steps:
步骤1,配制体积分数为20%的双氧水溶液,将药物按照5mg/ml质量体积百分比同时溶解在双氧水溶液中,简称溶液A;配制浓度为75mg/ml聚乙二醇(PEG)溶液,简称溶液B;配制浓度100μg/ml的过氧化氢酶溶液,简称溶液C;药物选用盐酸万古霉素;PEG为PEG2000;Step 1, prepare a 20% volume fraction hydrogen peroxide solution, dissolve the drug in the hydrogen peroxide solution at a mass volume percentage of 5 mg/ml, referred to as solution A; prepare a 75 mg/ml polyethylene glycol (PEG) solution, referred to as solution B; prepare a 100 μg/ml catalase solution, referred to as solution C; the drug is vancomycin hydrochloride; PEG is PEG2000;
步骤2,首先按溶液体积的20%(mg/ml),将一定质量的蒙脱土超声均匀分散于溶液A中,然后搅拌1h进行过氧化氢及药物负载,搅拌结束后抽滤,真空干燥;然后将一次干燥后的蒙脱土重新分散于溶液B中进行PEG包覆搅拌,搅拌时间为1h,搅拌结束后抽滤,真空干燥;最后将二次干燥后的蒙脱土重新分散于溶液C中进行过氧化氢酶的搭载,搅拌时间为1h,搅拌结束后抽滤,真空干燥;重复本步骤3次,利用层层自组装技术得到载双氧水/抗生素零级释放载体;Step 2, firstly, a certain mass of montmorillonite is uniformly dispersed in solution A by ultrasonic according to 20% (mg/ml) of the solution volume, and then stirred for 1 hour for hydrogen peroxide and drug loading, filtered after stirring, and vacuum dried; then the montmorillonite after the primary drying is redispersed in solution B for PEG coating and stirring, the stirring time is 1 hour, filtered after stirring, and vacuum dried; finally, the montmorillonite after the secondary drying is redispersed in solution C for catalase loading, the stirring time is 1 hour, filtered after stirring, and vacuum dried; repeat this step 3 times, and obtain a zero-order release carrier loaded with hydrogen peroxide/antibiotics by using layer-by-layer self-assembly technology;
步骤3,将PMMA粉体、引发剂BPO以及步骤2得到的载双氧水/抗生素零级释放载体按照质量比49.95:0.05:50混合均匀,得到填充固定材料成分D;Step 3, PMMA powder, initiator BPO and the hydrogen peroxide/antibiotic zero-order release carrier obtained in step 2 are mixed evenly in a mass ratio of 49.95:0.05:50 to obtain a filling and fixing material component D;
步骤4,将MMA、N,N-二甲基对甲苯胺、对苯二酚按质量比为96.5:3:0.5混合均匀,得到填充固定材料成分E;Step 4, MMA, N,N-dimethyl-p-toluidine, and hydroquinone are uniformly mixed in a mass ratio of 96.5:3:0.5 to obtain a filling and fixing material component E;
步骤5,将步骤3得到的填充固定材料成分D与步骤4得到的填充固定材料成分E按照固液比为1g/ml混合,搅拌,通过注射形式对开放性创伤部位进行填充,待填充固定材料成分D与填充固定材料成分E反应结束后,即可对创伤部位进行进一步的固定。Step 5, mix the filling and fixing material component D obtained in step 3 and the filling and fixing material component E obtained in step 4 at a solid-liquid ratio of 1g/ml, stir, and fill the open wound site by injection. After the reaction between the filling and fixing material component D and the filling and fixing material component E is completed, the wound site can be further fixed.
实施例2Example 2
本发明自供氧抗菌填充固定材料的制备方法的具体过程为:The specific process of the preparation method of the self-oxygen-supplying antibacterial filling and fixing material of the present invention is as follows:
步骤1,配制体积分数为40%的双氧水溶液,将药物按照15mg/ml质量体积百分比同时溶解在双氧水溶液中,简称溶液A;配制浓度为115mg/ml聚乙二醇(PEG)溶液,简称溶液B;配制浓度400μg/ml的过氧化氢酶溶液,简称溶液C;药物选用盐酸左氧氟沙星;PEG为PEG4000;Step 1, prepare a 40% volume fraction hydrogen peroxide solution, dissolve the drug in the hydrogen peroxide solution at a mass volume percentage of 15 mg/ml, referred to as solution A; prepare a polyethylene glycol (PEG) solution with a concentration of 115 mg/ml, referred to as solution B; prepare a catalase solution with a concentration of 400 μg/ml, referred to as solution C; the drug is levofloxacin hydrochloride; PEG is PEG4000;
步骤2,按溶液体积的40%(mg/ml),将一定质量的蒙脱土超声均匀分散于溶液A中,然后搅拌2h进行过氧化氢及药物负载,搅拌结束后抽滤,真空干燥;然后将一次干燥后的蒙脱土重新分散于溶液B中进行PEG包覆搅拌,搅拌时间为2h,搅拌结束后抽滤,真空干燥;最后将二次干燥后的蒙脱土重新分散于溶液C中进行过氧化氢酶的搭载,搅拌时间为2h,搅拌结束后抽滤,真空干燥;重复本步骤8次,利用层层自组装技术得到载双氧水/抗生素零级释放载体;Step 2, according to 40% (mg/ml) of the volume of the solution, a certain mass of montmorillonite is uniformly dispersed in solution A by ultrasonication, and then stirred for 2 hours for hydrogen peroxide and drug loading, filtered after stirring, and vacuum dried; then the montmorillonite after the primary drying is redispersed in solution B for PEG coating and stirring, the stirring time is 2 hours, filtered after stirring, and vacuum dried; finally, the montmorillonite after the secondary drying is redispersed in solution C for catalase loading, the stirring time is 2 hours, filtered after stirring, and vacuum dried; repeat this step 8 times, and obtain a zero-order release carrier loaded with hydrogen peroxide/antibiotics by using layer-by-layer self-assembly technology;
步骤3,将PMMA粉体、引发剂BPO以及步骤2得到的载双氧水/抗生素零级释放载体按照质量比69.85:0.15:30混合均匀,得到填充固定材料成分D;Step 3, PMMA powder, initiator BPO and the hydrogen peroxide/antibiotic zero-order release carrier obtained in step 2 are mixed evenly in a mass ratio of 69.85:0.15:30 to obtain a filling and fixing material component D;
步骤4,将MMA、N,N-二甲基对甲苯胺、对苯二酚按质量比为99.5:0.4:0.1混合均匀,得到填充固定材料成分E;Step 4, MMA, N,N-dimethyl-p-toluidine, and hydroquinone are mixed uniformly at a mass ratio of 99.5:0.4:0.1 to obtain a filling and fixing material component E;
步骤5,将步骤3得到的填充固定材料成分D与步骤4得到的填充固定材料成分E按照固液比为2g/ml混合,搅拌,通过注射形式对开放性骨折部位进行填充,待填充固定材料成分D与填充固定材料成分E反应结束后,即可对创伤部位进行进一步的固定。Step 5, mix the filling and fixing material component D obtained in step 3 and the filling and fixing material component E obtained in step 4 at a solid-liquid ratio of 2g/ml, stir, and fill the open fracture site by injection. After the reaction between the filling and fixing material component D and the filling and fixing material component E is completed, the trauma site can be further fixed.
实施例3Example 3
本发明自供氧抗菌填充固定材料的制备方法的具体过程为:The specific process of the preparation method of the self-oxygen-supplying antibacterial filling and fixing material of the present invention is as follows:
步骤1,配制体积分数为25%的双氧水溶液,将药物按照7.5mg/ml质量体积百分比同时溶解在双氧水溶液中,简称溶液A;配制浓度为85mg/ml聚乙二醇(PEG)溶液,简称溶液B;配制浓度200μg/ml的过氧化氢酶溶液,简称溶液C;药物选用盐酸四环素,PEG为PEG6000;Step 1, prepare a 25% volume fraction hydrogen peroxide solution, dissolve the drug in the hydrogen peroxide solution at a mass volume percentage of 7.5 mg/ml, referred to as solution A; prepare a polyethylene glycol (PEG) solution with a concentration of 85 mg/ml, referred to as solution B; prepare a catalase solution with a concentration of 200 μg/ml, referred to as solution C; the drug is tetracycline hydrochloride, and the PEG is PEG6000;
步骤2,按溶液体积的25%(mg/ml),将一定质量的蒙脱土超声均匀分散于溶液A中,然后搅拌2h进行过氧化氢及药物负载,搅拌结束后抽滤,真空干燥,然后将一次干燥后的蒙脱土重新分散于溶液B中进行PEG包覆搅拌,搅拌时间为2h,搅拌结束后抽滤,真空干燥,最后将二次干燥后的蒙脱土重新分散于溶液C中进行过氧化氢酶的搭载,搅拌时间为2h,搅拌结束后抽滤,真空干燥;重复本步骤4次,利用层层自组装技术得到载双氧水/抗生素零级释放载体;Step 2, according to 25% (mg/ml) of the volume of the solution, a certain mass of montmorillonite is uniformly dispersed in solution A by ultrasonication, and then stirred for 2 hours for hydrogen peroxide and drug loading, filtered after stirring, vacuum dried, and then the once dried montmorillonite is redispersed in solution B for PEG coating and stirring, the stirring time is 2 hours, filtered after stirring, vacuum dried, and finally the secondary dried montmorillonite is redispersed in solution C for catalase loading, the stirring time is 2 hours, filtered after stirring, and vacuum dried; repeat this step 4 times, and use layer-by-layer self-assembly technology to obtain a zero-order release carrier loaded with hydrogen peroxide/antibiotics;
步骤3,将PMMA粉体、引发剂BPO以及步骤2得到的载双氧水/抗生素零级释放载体按照质量比64.85:0.15:35混合均匀,得到填充固定材料成分D;Step 3, PMMA powder, initiator BPO and the hydrogen peroxide/antibiotic zero-order release carrier obtained in step 2 are mixed evenly in a mass ratio of 64.85:0.15:35 to obtain a filling and fixing material component D;
步骤4,将MMA、N,N-二甲基对甲苯胺、对苯二酚按质量比为98.5:1:0.5混合均匀,得到填充固定材料成分E;Step 4, MMA, N,N-dimethyl-p-toluidine, and hydroquinone are mixed uniformly at a mass ratio of 98.5:1:0.5 to obtain a filling and fixing material component E;
步骤5,将步骤3得到的填充固定材料成分D与步骤4得到的填充固定材料成分E按照固液比为1.5g/ml混合,搅拌,通过注射形式对开放性骨折部位进行填充,待填充固定材料成分D与填充固定材料成分E反应结束后,即可对创伤部位进行进一步的固定。Step 5, mix the filling and fixing material component D obtained in step 3 and the filling and fixing material component E obtained in step 4 at a solid-liquid ratio of 1.5 g/ml, stir, and fill the open fracture site by injection. After the reaction between the filling and fixing material component D and the filling and fixing material component E is completed, the trauma site can be further fixed.
实施例4Example 4
本发明自供氧抗菌填充固定材料的制备方法的具体过程为:The specific process of the preparation method of the self-oxygen-supplying antibacterial filling and fixing material of the present invention is as follows:
步骤1,配制体积分数为30%的双氧水溶液,将药物按照10mg/ml质量体积百分比同时溶解在双氧水溶液中,简称溶液A;配制浓度为115mg/ml聚乙二醇(PEG)溶液,简称溶液B;配制浓度300μg/ml的过氧化氢酶溶液,简称溶液C;药物选用头孢曲松钠,PEG为PEG8000;Step 1, prepare a 30% volume fraction hydrogen peroxide solution, dissolve the drug in the hydrogen peroxide solution at a mass volume percentage of 10 mg/ml, referred to as solution A; prepare a polyethylene glycol (PEG) solution with a concentration of 115 mg/ml, referred to as solution B; prepare a catalase solution with a concentration of 300 μg/ml, referred to as solution C; the drug is ceftriaxone sodium, and the PEG is PEG8000;
步骤2,按溶液体积的30%(mg/ml),将一定质量的蒙脱土超声均匀分散于溶液A中,然后搅拌1.5h进行过氧化氢及药物负载,搅拌结束后抽滤,真空干燥;然后将一次干燥后的蒙脱土重新分散于溶液B中进行PEG包覆搅拌,搅拌时间为2h,搅拌结束后抽滤,真空干燥;最后将二次干燥后的蒙脱土重新分散于溶液C中进行过氧化氢酶的搭载,搅拌时间为1.5h,搅拌结束后抽滤,真空干燥;重复本步骤5次,利用层层自组装技术得到载双氧水/抗生素零级释放载体;Step 2, according to 30% (mg/ml) of the volume of the solution, a certain mass of montmorillonite is uniformly dispersed in solution A by ultrasonication, and then stirred for 1.5 hours for hydrogen peroxide and drug loading, filtered after stirring, and vacuum dried; then the montmorillonite after the primary drying is redispersed in solution B for PEG coating and stirring, the stirring time is 2 hours, filtered after stirring, and vacuum dried; finally, the montmorillonite after the secondary drying is redispersed in solution C for catalase loading, the stirring time is 1.5 hours, filtered after stirring, and vacuum dried; repeat this step 5 times, and obtain a zero-order release carrier loaded with hydrogen peroxide/antibiotics by using layer-by-layer self-assembly technology;
步骤3,将PMMA粉体、引发剂BPO以及步骤2得到的载双氧水/抗生素零级释放载体按照质量比62.95:0.05:37混合均匀,得到填充固定材料成分D;Step 3, PMMA powder, initiator BPO and the hydrogen peroxide/antibiotic zero-order release carrier obtained in step 2 are mixed evenly in a mass ratio of 62.95:0.05:37 to obtain a filling and fixing material component D;
步骤4,将MMA、N,N-二甲基对甲苯胺、对苯二酚按质量比为97.5:2.1:0.4混合均匀,得到填充固定材料成分E;Step 4, MMA, N,N-dimethyl-p-toluidine, and hydroquinone are mixed uniformly at a mass ratio of 97.5:2.1:0.4 to obtain a filling and fixing material component E;
步骤5,将步骤3得到的填充固定材料成分D与步骤4得到的填充固定材料成分E按照固液比为2g/ml混合,搅拌,通过注射形式对开放性骨折部位进行填充,待填充固定材料成分D与填充固定材料成分E反应结束后,即可对创伤部位进行进一步的固定。Step 5, mix the filling and fixing material component D obtained in step 3 and the filling and fixing material component E obtained in step 4 at a solid-liquid ratio of 2g/ml, stir, and fill the open fracture site by injection. After the reaction between the filling and fixing material component D and the filling and fixing material component E is completed, the trauma site can be further fixed.
实施例5Example 5
本发明自供氧抗菌填充固定材料的制备方法的具体过程为:The specific process of the preparation method of the self-oxygen-supplying antibacterial filling and fixing material of the present invention is as follows:
步骤1,配制体积分数为35%的双氧水溶液,将药物按照15mg/ml质量体积百分比同时溶解在双氧水溶液中,简称溶液A,配制浓度为115mg/ml聚乙二醇(PEG)溶液,简称溶液B;配制浓度350μg/ml的过氧化氢酶溶液,简称溶液C;药物为盐酸万古霉素,PEG为PEG10000;Step 1, prepare a 35% volume fraction hydrogen peroxide solution, dissolve the drug in the hydrogen peroxide solution at a mass volume percentage of 15 mg/ml, referred to as solution A, prepare a 115 mg/ml polyethylene glycol (PEG) solution, referred to as solution B; prepare a 350 μg/ml catalase solution, referred to as solution C; the drug is vancomycin hydrochloride, and the PEG is PEG10000;
步骤2,按溶液体积的40%(mg/ml),将一定质量的蒙脱土超声均匀分散于溶液A中,然后搅拌2h进行过氧化氢及药物负载,搅拌结束后抽滤,真空干燥;然后将一次干燥后的蒙脱土重新分散于溶液B中进行PEG包覆搅拌,搅拌时间为2h,搅拌结束后抽滤,真空干燥;最后将二次干燥后的蒙脱土重新分散于溶液C中进行过氧化氢酶的搭载,搅拌时间为1h,搅拌结束后抽滤,真空干燥;重复本步骤7次,利用层层自组装技术得到载双氧水/抗生素零级释放载体;Step 2, according to 40% (mg/ml) of the volume of the solution, a certain mass of montmorillonite is uniformly dispersed in solution A by ultrasonication, and then stirred for 2 hours for hydrogen peroxide and drug loading, filtered after stirring, and vacuum dried; then the montmorillonite after the primary drying is redispersed in solution B for PEG coating and stirring, the stirring time is 2 hours, filtered after stirring, and vacuum dried; finally, the montmorillonite after the secondary drying is redispersed in solution C for catalase loading, the stirring time is 1 hour, filtered after stirring, and vacuum dried; repeat this step 7 times, and obtain a zero-order release carrier loaded with hydrogen peroxide/antibiotics by using layer-by-layer self-assembly technology;
步骤3,将PMMA粉体、引发剂BPO以及步骤2得到的载双氧水/抗生素零级释放载体按照质量比59.85:0.15:40混合均匀,得到填充固定材料成分D;Step 3, PMMA powder, initiator BPO and the hydrogen peroxide/antibiotic zero-order release carrier obtained in step 2 are mixed evenly in a mass ratio of 59.85:0.15:40 to obtain a filling and fixing material component D;
步骤4,将MMA、N,N-二甲基对甲苯胺、对苯二酚按质量比为96.5~99.5:0.3~3:0.1~0.5混合均匀,得到填充固定材料成分E;Step 4, MMA, N,N-dimethyl-p-toluidine, and hydroquinone are uniformly mixed in a mass ratio of 96.5-99.5:0.3-3:0.1-0.5 to obtain a filling and fixing material component E;
步骤5,将步骤3得到的填充固定材料成分D与步骤4得到的填充固定材料成分E按照固液比为1g/ml混合,搅拌,通过注射形式对开放性骨折部位进行填充,待填充固定材料成分D与填充固定材料成分E反应结束后,即可对创伤部位进行进一步的固定。Step 5, mix the filling and fixing material component D obtained in step 3 and the filling and fixing material component E obtained in step 4 at a solid-liquid ratio of 1g/ml, stir, and fill the open fracture site by injection. After the reaction between the filling and fixing material component D and the filling and fixing material component E is completed, the trauma site can be further fixed.
经实验证明,本发明制备方法得到的自供氧抗菌填充固定材料在模拟人体环境下的氧气释放以及抗生素的释放遵循零级释放动力学,避免因药物以及氧气突释导致的副作用,同时经临床实验使用后,材料的固定性、感染预防及抗菌治疗均表现良好。Experiments have shown that the oxygen release and antibiotic release of the self-oxygenated antibacterial filling and fixing material obtained by the preparation method of the present invention in a simulated human body environment follow zero-order release kinetics, avoiding side effects caused by sudden release of drugs and oxygen. At the same time, after clinical experimental use, the material's fixation, infection prevention and antibacterial treatment all performed well.
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