CN115475285A - 有梯度释药功能的双载药胶原基屏障膜及制备方法和应用 - Google Patents
有梯度释药功能的双载药胶原基屏障膜及制备方法和应用 Download PDFInfo
- Publication number
- CN115475285A CN115475285A CN202211184186.1A CN202211184186A CN115475285A CN 115475285 A CN115475285 A CN 115475285A CN 202211184186 A CN202211184186 A CN 202211184186A CN 115475285 A CN115475285 A CN 115475285A
- Authority
- CN
- China
- Prior art keywords
- drug
- collagen
- solution
- loaded
- barrier membrane
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 102000008186 Collagen Human genes 0.000 title claims abstract description 77
- 108010035532 Collagen Proteins 0.000 title claims abstract description 77
- 229920001436 collagen Polymers 0.000 title claims abstract description 77
- 239000012528 membrane Substances 0.000 title claims abstract description 59
- 239000003814 drug Substances 0.000 title claims abstract description 58
- 229940079593 drug Drugs 0.000 title claims abstract description 56
- 230000004888 barrier function Effects 0.000 title claims abstract description 48
- 238000002360 preparation method Methods 0.000 title claims abstract description 16
- 238000011068 loading method Methods 0.000 title claims abstract description 10
- 239000000693 micelle Substances 0.000 claims abstract description 34
- -1 dialdehyde polysaccharide Chemical class 0.000 claims abstract description 21
- 229920001282 polysaccharide Polymers 0.000 claims abstract description 21
- 239000005017 polysaccharide Substances 0.000 claims abstract description 21
- 229940124599 anti-inflammatory drug Drugs 0.000 claims abstract description 19
- 239000002260 anti-inflammatory agent Substances 0.000 claims abstract description 17
- 229940124350 antibacterial drug Drugs 0.000 claims abstract description 14
- 239000003431 cross linking reagent Substances 0.000 claims abstract description 9
- 125000003172 aldehyde group Chemical group 0.000 claims abstract description 8
- 238000004132 cross linking Methods 0.000 claims abstract description 6
- 238000006243 chemical reaction Methods 0.000 claims abstract description 4
- 239000002262 Schiff base Substances 0.000 claims abstract description 3
- 150000004753 Schiff bases Chemical class 0.000 claims abstract description 3
- 239000000243 solution Substances 0.000 claims description 93
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 36
- 239000008367 deionised water Substances 0.000 claims description 25
- 229910021641 deionized water Inorganic materials 0.000 claims description 25
- ZNZYKNKBJPZETN-WELNAUFTSA-N Dialdehyde 11678 Chemical compound N1C2=CC=CC=C2C2=C1[C@H](C[C@H](/C(=C/O)C(=O)OC)[C@@H](C=C)C=O)NCC2 ZNZYKNKBJPZETN-WELNAUFTSA-N 0.000 claims description 17
- 238000000034 method Methods 0.000 claims description 16
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 15
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 15
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 12
- VFLDPWHFBUODDF-FCXRPNKRSA-N curcumin Chemical compound C1=C(O)C(OC)=CC(\C=C\C(=O)CC(=O)\C=C\C=2C=C(OC)C(O)=CC=2)=C1 VFLDPWHFBUODDF-FCXRPNKRSA-N 0.000 claims description 12
- 238000004108 freeze drying Methods 0.000 claims description 11
- 239000000839 emulsion Substances 0.000 claims description 10
- 229920001661 Chitosan Polymers 0.000 claims description 9
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 9
- HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 claims description 9
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 9
- 229960001680 ibuprofen Drugs 0.000 claims description 9
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 8
- 102000000503 Collagen Type II Human genes 0.000 claims description 8
- 108010041390 Collagen Type II Proteins 0.000 claims description 8
- 230000003110 anti-inflammatory effect Effects 0.000 claims description 8
- 239000000203 mixture Substances 0.000 claims description 8
- 230000000844 anti-bacterial effect Effects 0.000 claims description 7
- 239000000463 material Substances 0.000 claims description 7
- SGKRLCUYIXIAHR-AKNGSSGZSA-N (4s,4ar,5s,5ar,6r,12ar)-4-(dimethylamino)-1,5,10,11,12a-pentahydroxy-6-methyl-3,12-dioxo-4a,5,5a,6-tetrahydro-4h-tetracene-2-carboxamide Chemical compound C1=CC=C2[C@H](C)[C@@H]([C@H](O)[C@@H]3[C@](C(O)=C(C(N)=O)C(=O)[C@H]3N(C)C)(O)C3=O)C3=C(O)C2=C1O SGKRLCUYIXIAHR-AKNGSSGZSA-N 0.000 claims description 6
- FFTVPQUHLQBXQZ-KVUCHLLUSA-N (4s,4as,5ar,12ar)-4,7-bis(dimethylamino)-1,10,11,12a-tetrahydroxy-3,12-dioxo-4a,5,5a,6-tetrahydro-4h-tetracene-2-carboxamide Chemical compound C1C2=C(N(C)C)C=CC(O)=C2C(O)=C2[C@@H]1C[C@H]1[C@H](N(C)C)C(=O)C(C(N)=O)=C(O)[C@@]1(O)C2=O FFTVPQUHLQBXQZ-KVUCHLLUSA-N 0.000 claims description 6
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 claims description 6
- 102000001187 Collagen Type III Human genes 0.000 claims description 6
- 108010069502 Collagen Type III Proteins 0.000 claims description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 6
- 239000004098 Tetracycline Substances 0.000 claims description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 6
- 229960001138 acetylsalicylic acid Drugs 0.000 claims description 6
- 229940109262 curcumin Drugs 0.000 claims description 6
- 235000012754 curcumin Nutrition 0.000 claims description 6
- 239000004148 curcumin Substances 0.000 claims description 6
- VFLDPWHFBUODDF-UHFFFAOYSA-N diferuloylmethane Natural products C1=C(O)C(OC)=CC(C=CC(=O)CC(=O)C=CC=2C=C(OC)C(O)=CC=2)=C1 VFLDPWHFBUODDF-UHFFFAOYSA-N 0.000 claims description 6
- 229960003722 doxycycline Drugs 0.000 claims description 6
- 238000007710 freezing Methods 0.000 claims description 6
- 230000008014 freezing Effects 0.000 claims description 6
- 239000007788 liquid Substances 0.000 claims description 6
- 229960004023 minocycline Drugs 0.000 claims description 6
- 229910052757 nitrogen Inorganic materials 0.000 claims description 6
- 229960002180 tetracycline Drugs 0.000 claims description 6
- 229930101283 tetracycline Natural products 0.000 claims description 6
- 235000019364 tetracycline Nutrition 0.000 claims description 6
- 150000003522 tetracyclines Chemical class 0.000 claims description 6
- 229920002134 Carboxymethyl cellulose Polymers 0.000 claims description 5
- 229920000858 Cyclodextrin Polymers 0.000 claims description 5
- 239000001768 carboxy methyl cellulose Substances 0.000 claims description 5
- 235000010948 carboxy methyl cellulose Nutrition 0.000 claims description 5
- 239000008112 carboxymethyl-cellulose Substances 0.000 claims description 5
- 238000001914 filtration Methods 0.000 claims description 5
- 239000011259 mixed solution Substances 0.000 claims description 5
- 239000000178 monomer Substances 0.000 claims description 5
- 239000000843 powder Substances 0.000 claims description 5
- 238000002390 rotary evaporation Methods 0.000 claims description 5
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 claims description 5
- 238000003756 stirring Methods 0.000 claims description 5
- 238000009210 therapy by ultrasound Methods 0.000 claims description 5
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 claims description 4
- 239000002202 Polyethylene glycol Substances 0.000 claims description 4
- 239000003960 organic solvent Substances 0.000 claims description 4
- 229920000747 poly(lactic acid) Polymers 0.000 claims description 4
- 229920001610 polycaprolactone Polymers 0.000 claims description 4
- 229920001223 polyethylene glycol Polymers 0.000 claims description 4
- 229920000642 polymer Polymers 0.000 claims description 4
- 102000012422 Collagen Type I Human genes 0.000 claims description 3
- 108010022452 Collagen Type I Proteins 0.000 claims description 3
- 239000011148 porous material Substances 0.000 claims description 3
- 102000004266 Collagen Type IV Human genes 0.000 claims description 2
- 108010042086 Collagen Type IV Proteins 0.000 claims description 2
- 229920002085 Dialdehyde starch Polymers 0.000 claims description 2
- 239000000679 carrageenan Substances 0.000 claims description 2
- 229920001525 carrageenan Polymers 0.000 claims description 2
- 235000010418 carrageenan Nutrition 0.000 claims description 2
- 229940113118 carrageenan Drugs 0.000 claims description 2
- WIIZWVCIJKGZOK-RKDXNWHRSA-N chloramphenicol Chemical compound ClC(Cl)C(=O)N[C@H](CO)[C@H](O)C1=CC=C([N+]([O-])=O)C=C1 WIIZWVCIJKGZOK-RKDXNWHRSA-N 0.000 claims description 2
- 229960005091 chloramphenicol Drugs 0.000 claims description 2
- 229960002152 chlorhexidine acetate Drugs 0.000 claims description 2
- 229960000905 indomethacin Drugs 0.000 claims description 2
- CGIGDMFJXJATDK-UHFFFAOYSA-N indomethacin Chemical compound CC1=C(CC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 CGIGDMFJXJATDK-UHFFFAOYSA-N 0.000 claims description 2
- 238000002156 mixing Methods 0.000 claims description 2
- 229960005489 paracetamol Drugs 0.000 claims description 2
- 229920001606 poly(lactic acid-co-glycolic acid) Polymers 0.000 claims description 2
- 239000004632 polycaprolactone Substances 0.000 claims description 2
- 229920002643 polyglutamic acid Polymers 0.000 claims description 2
- MCSINKKTEDDPNK-UHFFFAOYSA-N propyl propionate Chemical compound CCCOC(=O)CC MCSINKKTEDDPNK-UHFFFAOYSA-N 0.000 claims 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 claims description 2
- 229960003767 alanine Drugs 0.000 claims 1
- 125000003277 amino group Chemical group 0.000 claims 1
- 238000001471 micro-filtration Methods 0.000 claims 1
- 239000010409 thin film Substances 0.000 claims 1
- 230000007547 defect Effects 0.000 abstract description 13
- 230000006870 function Effects 0.000 abstract description 10
- 206010061218 Inflammation Diseases 0.000 abstract description 5
- 238000006731 degradation reaction Methods 0.000 abstract description 5
- 230000008901 benefit Effects 0.000 abstract description 4
- 230000015556 catabolic process Effects 0.000 abstract description 4
- 230000004054 inflammatory process Effects 0.000 abstract description 3
- 238000007634 remodeling Methods 0.000 abstract description 3
- 230000003115 biocidal effect Effects 0.000 abstract description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 abstract description 2
- 230000001737 promoting effect Effects 0.000 abstract 1
- 210000000988 bone and bone Anatomy 0.000 description 16
- 230000013632 homeostatic process Effects 0.000 description 5
- 102000004169 proteins and genes Human genes 0.000 description 5
- 108090000623 proteins and genes Proteins 0.000 description 5
- 230000003013 cytotoxicity Effects 0.000 description 4
- 231100000135 cytotoxicity Toxicity 0.000 description 4
- 239000002245 particle Substances 0.000 description 4
- 230000008929 regeneration Effects 0.000 description 4
- 238000011069 regeneration method Methods 0.000 description 4
- 210000001519 tissue Anatomy 0.000 description 4
- 150000001299 aldehydes Chemical class 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 238000002513 implantation Methods 0.000 description 3
- 201000001245 periodontitis Diseases 0.000 description 3
- 210000004872 soft tissue Anatomy 0.000 description 3
- SXRSQZLOMIGNAQ-UHFFFAOYSA-N Glutaraldehyde Chemical compound O=CCCCC=O SXRSQZLOMIGNAQ-UHFFFAOYSA-N 0.000 description 2
- 229940024606 amino acid Drugs 0.000 description 2
- 150000001413 amino acids Chemical class 0.000 description 2
- 230000001580 bacterial effect Effects 0.000 description 2
- 230000033228 biological regulation Effects 0.000 description 2
- 230000000903 blocking effect Effects 0.000 description 2
- 230000010478 bone regeneration Effects 0.000 description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
- 239000002131 composite material Substances 0.000 description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- 210000000963 osteoblast Anatomy 0.000 description 2
- 230000003239 periodontal effect Effects 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 230000008439 repair process Effects 0.000 description 2
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- 239000005057 Hexamethylene diisocyanate Substances 0.000 description 1
- 229920000954 Polyglycolide Polymers 0.000 description 1
- 241000191967 Staphylococcus aureus Species 0.000 description 1
- 238000003917 TEM image Methods 0.000 description 1
- 208000008312 Tooth Loss Diseases 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 244000052616 bacterial pathogen Species 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 238000006065 biodegradation reaction Methods 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000002308 calcification Effects 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 230000012292 cell migration Effects 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000010382 chemical cross-linking Methods 0.000 description 1
- 230000001186 cumulative effect Effects 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- RRAMGCGOFNQTLD-UHFFFAOYSA-N hexamethylene diisocyanate Chemical compound O=C=NCCCCCCN=C=O RRAMGCGOFNQTLD-UHFFFAOYSA-N 0.000 description 1
- 230000007365 immunoregulation Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000028709 inflammatory response Effects 0.000 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- 230000000813 microbial effect Effects 0.000 description 1
- 210000000214 mouth Anatomy 0.000 description 1
- 239000002086 nanomaterial Substances 0.000 description 1
- 229920005615 natural polymer Polymers 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- 230000035764 nutrition Effects 0.000 description 1
- 238000002464 physical blending Methods 0.000 description 1
- 229920001553 poly(ethylene glycol)-block-polylactide methyl ether Polymers 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 230000002522 swelling effect Effects 0.000 description 1
- 230000017423 tissue regeneration Effects 0.000 description 1
Images
Classifications
-
- 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
- A61L31/044—Collagen
-
- 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
- A61L31/042—Polysaccharides
-
- 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
-
- 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
- A61L31/146—Porous materials, e.g. foams or sponges
-
- 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
- A61L31/148—Materials at least partially resorbable by the body
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/404—Biocides, antimicrobial agents, antiseptic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- 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
-
- 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
- A61L2300/41—Anti-inflammatory agents, e.g. NSAIDs
-
- 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
Abstract
本发明公开了一种有梯度释药功能的双载药胶原基屏障膜及制备方法和应用，以胶原为基材，采用纳米胶束技术将两种具有免疫稳态调节功能的抗菌抗炎药物引入屏障膜中。采用无生物毒性的双醛多糖作为交联剂，通过胶原氨基与双醛多糖的醛基发生席夫碱交联反应构建多孔胶原基屏障膜。本发明的优点是：双醛多糖交联的胶原基屏障膜，具有较高的机械强度、可控的降解速率、良好的生物相容性和组织贴合性，纳米胶束载药技术赋予屏障膜抗菌、抗炎和促进炎症消退的免疫稳态重塑功能，并实现抗菌药物的快速释放以及抗炎药物的长效缓释的梯度释放性能，解决了现有胶原基屏障膜所存在的技术缺陷。
Description
技术领域
本发明涉及生物医用材料技术领域，具体而言涉及一种有梯度释药功能的双载药胶原基屏障膜及制备方法和应用，为具有较强机械性能、可控生物降解速率、双药梯度释放且具有免疫稳态调节功能的多孔胶原基骨缺损修复屏障膜。
背景技术
随着人们生活水平的不断提高，牙齿种植的需求量正处于高速增长期。牙槽骨是牙种植和口腔功能修复重建的基础，牙槽骨缺损是牙种植面临的巨大挑战。引导性骨组织再生术(Guided bone regeneration，GBR)是目前最有效的牙槽骨缺损重建技术，其原理是在软组织与骨缺损区之间放置阻隔软组织细胞的屏障膜，为成骨细胞提供优势生长的三维空间，实现骨缺损的自主性再生。与其他屏障膜相比，胶原膜在骨缺损修复方面具有其独特的优势，目前临床上使用的屏障膜有75％以上是胶原膜。胶原具有抗原性弱、生物相容性好、植入体内无排异反应、与组织亲和力强等独特的生物学活性；而且具有生物可降解性，植入体内后会慢慢降解释放大量的氨基酸，为骨再生提供充足的营养。此外胶原还可刺激诱导成骨细胞的增殖分化，具有引导骨组织再生和防止骨不连的作用。
然而，目前使用的胶原膜存在机械强度低、降解速度快以及缺乏抗菌抗炎活性等缺点，无法适应牙周炎以及牙槽骨缺损患处的微环境，从而无法实现最佳的牙槽骨重建效果。研究者们通过交联、添加无机纳米材料或与其他高分子共混等方式来改善胶原膜的机械性能。化学交联常用的交联剂戊二醛可以提高胶原膜机械性能，但在膜降解过程中戊二醛会缓慢释放，引起炎症反应和钙化作用。交联剂1-(3-二甲氨基丙基)-3-乙基碳二亚胺盐酸盐和六亚甲基二异氰酸酯的细胞毒性相对较低，但会降低胶原膜诱导骨组织再生的能力。研究发现，双醛多糖作为大分子醛类交联剂与蛋白质分子之间会形成复杂的互穿网络结构，克服了小分子醛类交联剂的溶出和细胞毒性问题；双醛多糖交联可以显著提高蛋白材料的机械性能，控制其降解速度和吸水溶胀性；此外，双醛多糖交联不会影响蛋白质分子链上亲水性基团羟基和羧基的数量，双醛多糖分子本身也含有大量的羟基和羧基，不会降低蛋白材料的亲水性和组织贴附能力。
牙周炎是造成牙槽骨缺损和成人失牙的主要原因。牙周炎是由牙菌斑微生物感染引起的牙周局部免疫稳态失衡造成的炎症性反应，从组织破坏到组织再生是一个从局部免疫稳态失衡到免疫稳态重塑的过程。理想状态下，屏障膜在发挥软组织阻隔作用的同时，持续缓释具有抗菌及免疫调节效应的药物成分，诱导良好的局部免疫微环境产生，将更有利于牙周组织的快速稳定再生。而目前大部分屏障膜负载的药物采用简单的掺杂方式，会导致药物的突释，不能起到长效抗炎杀菌的功能，同时局部药物浓度过高会产生一定的细胞毒性导致局部菌群失调。
因此，构建一种具有一定机械强度和生物相容性，且贴合牙槽骨重建周期进行梯度释药维持免疫稳态的胶原基屏障膜具有重要的应用前景。
发明内容
本发明针对现有技术的缺陷，提供了一种有梯度释药功能的双载药胶原基屏障膜及制备方法和应用。
本发明以胶原为基材，采用双醛多糖作为交联剂，通过胶原氨基与双醛多糖的醛基发生席夫碱交联反应构建多孔胶原基屏障膜。采用纳米胶束技术将两种具有免疫稳态调节功能的抗菌抗炎药物引入屏障膜中，赋予屏障膜抗菌、抗炎和促进炎症消退的免疫稳态重塑功能，并实现抗菌药物的快速释放以及抗炎药物的长效缓释的梯度释放性能，解决了现有胶原基屏障膜所存在的技术缺陷。
为了实现以上发明目的，本发明采取的技术方案如下：
(1)载药胶束溶液的制备：将5～50质量份两亲性聚合物单体和1质量份抗炎药物溶于1～5体积份的有机溶剂制备油相，在0～40℃下超声1～5min使样品充分溶解。将油相加入20体积份的去离子水中，以500～13000rpm的转速高速匀质2～10min获得乳液，将乳液在30～60℃下进行旋转蒸发，直至溶液挥发完全，加入5～20体积份的去离子水复溶，采用0.22～0.80μm的微孔滤膜过滤器对所得溶液进行过滤，最后冷冻干燥获得载抗炎药纳米胶束。将所得的载抗炎药纳米胶束粉末溶于去离子水中得到质量浓度为0.01％～2％的载抗炎药胶束溶液备用。
(2)胶原基屏障膜的制备：将胶原溶于0.1～1M的醋酸溶液中得到质量分数为0.1％～2％的胶原溶液，将抗菌药物溶于去离子水中得到质量浓度为0.01％～2％的抗菌药物溶液。将抗菌药物溶液加入胶原溶液中，使抗菌药物的最终质量浓度为0.005％～1％，将载抗炎药胶束溶液加入胶原溶液中，使载抗炎药胶束溶液的最终质量浓度为0.005％～1％，冰浴下搅拌2～24h使其混合均匀。使用0.25～3M的氢氧化钠溶液调节载药胶原溶液pH至5～8。将醛基含量为0.5～5mmol/g的双醛多糖溶于去离子水中，得到质量浓度为0.05％～1％的双醛多糖溶液。在冰浴下将1体积份双醛多糖溶液缓慢加入到10～50体积份的胶原溶液中，然后将混合溶液倒入模具中，在液氮中冷冻30～240S后冷冻干燥得到双载药胶原基屏障膜。
作为优选，所述两亲性聚合物为壳聚糖(CS)-聚己内酯(PCL)、聚乙二醇(PEG)-聚丙交酯(PLA)、PEG-胆固醇(Chol)、PEG-聚乙交酯(PGA)、PEG-聚(乙交酯-co-丙交酯)(PLGA)中任意一种或几种的混合物。
作为优选，所述有机溶剂为乙醇、甲醇、二氯甲烷、丙酮、乙酸乙酯、甲苯中的任意一种或几种的混合物。
作为优选，所述抗炎药物为阿司匹林、对乙酰氨基酚、布洛芬、姜黄素、吲哚美辛中的任意一种。
作为优选，所述抗菌药物为ε-聚耐氨酸、米诺环素、氯霉素、醋酸氯己定、四环素、多西环素中的任意一种。
作为优选，所述胶原为Ⅰ型胶原、Ⅱ型胶原、Ⅲ型胶原、Ⅳ型胶原中的任意一种。
作为优选，所述双醛多糖为双醛淀粉、双醛环糊精、双醛羧甲基纤维素、双醛壳聚糖、双醛卡拉胶中的任意一种。
本发明获得的产物，作为梯度释药的载药材料。
与现有技术相比，本发明的优点在于：
(1)本发明以天然高分子为原材料，制备的多孔胶原基骨缺损修复屏障膜具有较高的机械强度、可控的降解速率、良好的生物相容性和组织贴合性；
(2)本发明采用双醛多糖作为交联剂避免了小分子醛类交联剂的细胞毒性问题，在不影响胶原本身生物相容性的基础上，提高了胶原基屏障膜的机械性能。
(3)本发明采用纳米胶束技术包载抗炎药物，物理共混方式掺入抗菌药物，可以实现抗菌药物快速释放，抗炎药物长效缓释的梯度递送效果，更好地顺应了牙槽骨缺损重建的微环境变化。
附图说明
图1(A)为实施例载药胶束的TEM图片；
图1(B)为实施例载药胶束的TEM粒径统计；
图1(C)为实施例载药胶束的DLS粒径分布统计；
图2(A)为实施例多孔胶原膜的SEM图片；
图2(B)为实施例多孔胶原膜的SEM孔径分布统计；
图3为实施例纯胶原膜与复合屏障膜对大肠杆菌和金黄色葡萄球菌的细菌渗透实验SEM图片；
图4为实施例抗炎药物与抗菌药物累积释放动力学曲线。
具体实施方式
为使本发明的目的、技术方案及优点更加清楚明白，以下列举实施例，对本发明做进一步详细说明。
实施例1
(1)载药胶束溶液的制备：将10质量份PEG-PLA单体和1质量份阿司匹林溶于3体积份的丙酮制备油相，在30℃下超声1min使样品充分溶解。将油相加入20体积份的去离子水中，以5000rpm的转速高速匀质4min获得乳液，将乳液在45℃下进行旋转蒸发，直至溶液挥发完全，加入10体积份的去离子水复溶，采用0.45μm的微孔滤膜过滤器对所得溶液进行过滤，最后冷冻干燥获得载阿司匹林纳米胶束。将所得的载阿司匹林纳米胶束粉末溶于去离子水中得到质量浓度为0.5％的载阿司匹林胶束溶液备用。
(2)胶原基屏障膜的制备：将Ⅰ型胶原溶于0.5M的醋酸溶液中得到质量分数为0.8％的Ⅰ型胶原溶液，将米诺环素溶于去离子水中得到质量浓度为0.5％的米诺环素溶液。将米诺环素溶液加入Ⅰ型胶原溶液中，使米诺环素的最终质量浓度为0.1％，将载阿司匹林胶束溶液加入Ⅰ型胶原溶液中，使载阿司匹林胶束溶液的最终质量浓度为0.1％，冰浴下搅拌12h使其混合均匀。使用0.25M的氢氧化钠溶液调节载药胶原溶液pH至5。将醛基含量为2mmol/g的双醛壳聚糖溶于去离子水中，得到质量浓度为0.3％的双醛壳聚糖溶液。在冰浴下将1体积份双醛壳聚糖溶液缓慢加入到10体积份的Ⅰ型胶原溶液中，然后将混合溶液倒入模具中，在液氮中冷冻60S后冷冻干燥得到双载药胶原基屏障膜。
实施例2
(1)载药胶束溶液的制备：将5质量份PEG-Chol单体和1质量份布洛芬溶于2体积份的二氯甲烷制备油相，在20℃下超声3min使样品充分溶解。将油相加入20体积份的去离子水中，以10000rpm的转速高速匀质5min获得乳液，将乳液在35℃下进行旋转蒸发，直至溶液挥发完全，加入10体积份的去离子水复溶，采用0.80μm的微孔滤膜过滤器对所得溶液进行过滤，最后冷冻干燥获得载布洛芬纳米胶束。将所得的载布洛芬纳米胶束粉末溶于去离子水中得到质量浓度为1％的载布洛芬胶束溶液备用。
(2)胶原基屏障膜的制备：将Ⅱ型胶原溶于0.1M的醋酸溶液中得到质量分数为0.5％的Ⅱ型胶原溶液，将四环素溶于去离子水中得到质量浓度为1％的四环素溶液。将四环素溶液加入Ⅱ型胶原溶液中，使四环素的最终质量浓度为0.05％，将载布洛芬胶束溶液加入Ⅱ型胶原溶液中，使载布洛芬胶束溶液的最终质量浓度为0.05％，冰浴下搅拌8h使其混合均匀。使用1M的氢氧化钠溶液调节载药胶原溶液pH至6。将醛基含量为4mmol/g的双醛环糊精溶于去离子水中，得到质量浓度为0.5％的双醛环糊精溶液。在冰浴下将1体积份双醛环糊精溶液缓慢加入到50体积份的Ⅱ型胶原溶液中，然后将混合溶液倒入模具中，在液氮中冷冻100S后冷冻干燥得到双载药胶原基屏障膜。
实施例3
(1)载药胶束溶液的制备：将20质量份PEG-PGA单体和1质量份姜黄素溶于5体积份的甲醇制备油相，在0℃下超声5min使样品充分溶解。将油相加入20体积份的去离子水中，以8000rpm的转速高速匀质5min获得乳液，将乳液在45℃下进行旋转蒸发，直至溶液挥发完全，加入10体积份的去离子水复溶，采用0.22μm的微孔滤膜过滤器对所得溶液进行过滤，最后冷冻干燥获得载姜黄素纳米胶束。将所得的载姜黄素纳米胶束粉末溶于去离子水中得到质量浓度为2％的载姜黄素胶束溶液备用。
(2)胶原基屏障膜的制备：将Ⅲ型胶原溶于0.5M的醋酸溶液中得到质量分数为1％的胶原溶液，将多西环素溶于去离子水中得到质量浓度为2％的多西环素溶液。将多西环素溶液加入Ⅲ型胶原溶液中，使多西环素的最终质量浓度为0.04％，将载姜黄素胶束溶液加入Ⅲ型胶原溶液中，使载抗炎药胶束溶液的最终质量浓度为0.04％，冰浴下搅拌24h使其混合均匀。使用2M的氢氧化钠溶液调节载药胶原溶液pH至7。将醛基含量为5mmol/g的双醛羧甲基纤维素溶于去离子水中，得到质量浓度为0.5％的双醛羧甲基纤维素溶液。在冰浴下将1体积份双醛羧甲基纤维素溶液缓慢加入到40体积份的Ⅲ型胶原溶液中，然后将混合溶液倒入模具中，在液氮中冷冻180S后冷冻干燥得到双载药胶原基屏障膜。
本发明提供以下实验数据：
如图1(A)到图1(C)所示，所制备的纳米胶束呈近球形，颗粒分布较为均匀且具有良好的分散性，粒径分布在50nm附近，且对抗炎药物成功包载。
如图2(A)到图2(B)所示，所示，所制备的屏障膜呈现均匀的多孔，孔径分布在70μm附近，为细胞迁移和增殖提供了空间。
如图3所示，与纯胶原膜相比，加入了药物的复合屏障膜，膜表面无活细菌附着，说明该屏障膜可以有效杀死致病菌。
如图4所示，A为抗菌药物，可在15d内快速释放90％的药物，B为抗炎药物，可以缓慢释放长达2个月，表明该体系可实现药物的梯度多级释放。
本领域的普通技术人员将会意识到，这里所述的实施例是为了帮助读者理解本发明的实施方法，应被理解为本发明的保护范围并不局限于这样的特别陈述和实施例。本领域的普通技术人员可以根据本发明公开的这些技术启示做出各种不脱离本发明实质的其它各种具体变形和组合，这些变形和组合仍然在本发明的保护范围内。
Claims (10)
1.有梯度释药功能的双载药胶原基屏障膜的制备方法，其特征在于，包括以下步骤：
采用乳化-薄膜挥发法制备载抗炎药纳米载药胶束，然后将载抗炎药纳米载药胶束溶液与抗菌药物溶液与胶原溶液混合均匀后，以无生物毒性的双醛多糖作为交联剂，通过双醛多糖的醛基与胶原的氨基之间的席夫碱反应进行交联，最后通过液氮冷冻、冷冻干燥得到双载药胶原基屏障膜。
2.根据权利要求1所述的一种有梯度释药功能的双载药胶原基屏障膜的制备方法，其特征在于，具体包括如下步骤：
(1)载药胶束溶液的制备：将5～50质量份两亲性聚合物单体和1质量份抗炎药物溶于1～5体积份的有机溶剂制备油相，在0～40℃下超声1～5min使样品充分溶解；将油相加入20体积份的去离子水中，以500～13000rpm的转速高速匀质2～10min获得乳液，将乳液在30～60℃下进行旋转蒸发，直至溶液挥发完全，加入5～20体积份的去离子水复溶，采用0.22～0.80μm的微孔滤膜过滤器对所得溶液进行过滤，最后冷冻干燥获得载抗炎药纳米胶束；将所得的载抗炎药纳米胶束粉末溶于去离子水中得到质量浓度为0.01％～2％的载抗炎药胶束溶液备用；
(2)胶原基屏障膜的制备：将胶原溶于0.1～1M的醋酸溶液中得到质量分数为0.1％～2％的胶原溶液，将抗菌药物溶于去离子水中得到质量浓度为0.01％～2％的抗菌药物溶液；将抗菌药物溶液加入胶原溶液中，使抗菌药物的最终质量浓度为0.005％～1％，将载抗炎药胶束溶液加入胶原溶液中，使载抗炎药胶束溶液的最终质量浓度为0.005％～1％，冰浴下搅拌2～24h使其混合均匀；使用0.25～3M的氢氧化钠溶液调节载药胶原溶液pH至5～8；将醛基含量为0.5～5mmol/g的双醛多糖溶于去离子水中，得到质量浓度为0.05％～1％的双醛多糖溶液；在冰浴下将1体积份双醛多糖溶液缓慢加入到10～50体积份的胶原溶液中，然后将混合溶液倒入模具中，在液氮中冷冻30～240S后冷冻干燥得到双载药胶原基屏障膜。
3.根据权利要求2所述的一种有梯度释药功能的双载药胶原基屏障膜的制备方法，其特征在于：所述两亲性聚合物为壳聚糖(CS)-聚己内酯(PCL)、聚乙二醇(PEG)-聚丙交酯(PLA)、PEG-胆固醇(Chol)、PEG-聚乙交酯(PGA)、PEG-聚(乙交酯-co-丙交酯)(PLGA)中任意一种或几种的混合物。
4.根据权利要求2所述的一种有梯度释药功能的双载药胶原基屏障膜的制备方法，其特征在于：所述有机溶剂为乙醇、甲醇、二氯甲烷、丙酮、乙酸乙酯、甲苯中的任意一种或几种的混合物。
5.根据权利要求2所述的一种有梯度释药功能的双载药胶原基屏障膜的制备方法，其特征在于：所述抗炎药物为阿司匹林、对乙酰氨基酚、布洛芬、姜黄素、吲哚美辛中的任意一种。
6.根据权利要求2所述的一种有梯度释药功能的双载药胶原基屏障膜的制备方法，其特征在于：所述抗菌药物为ε-聚耐氨酸、米诺环素、氯霉素、醋酸氯己定、四环素、多西环素中的任意一种。
7.根据权利要求2所述的一种有梯度释药功能的双载药胶原基屏障膜的制备方法，其特征在于：所述胶原为Ⅰ型胶原、Ⅱ型胶原、Ⅲ型胶原、Ⅳ型胶原中的任意一种。
8.根据权利要求2所述的一种有梯度释药功能的双载药胶原基屏障膜的制备方法，其特征在于：所述双醛多糖为双醛淀粉、双醛环糊精、双醛羧甲基纤维素、双醛壳聚糖、双醛卡拉胶中的任意一种。
9.根据权利要求1到8任一项制备方法所得的一种有梯度释药功能的双载药胶原基屏障膜。
10.根据权利要求9所述的一种具有梯度释药功能的双载药胶原基屏障膜的应用，其特征在于，用于载药材料。
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202211184186.1A CN115475285A (zh) | 2022-09-27 | 2022-09-27 | 有梯度释药功能的双载药胶原基屏障膜及制备方法和应用 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202211184186.1A CN115475285A (zh) | 2022-09-27 | 2022-09-27 | 有梯度释药功能的双载药胶原基屏障膜及制备方法和应用 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN115475285A true CN115475285A (zh) | 2022-12-16 |
Family
ID=84394188
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202211184186.1A Pending CN115475285A (zh) | 2022-09-27 | 2022-09-27 | 有梯度释药功能的双载药胶原基屏障膜及制备方法和应用 |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN115475285A (zh) |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1529653A (zh) * | 2001-05-16 | 2004-09-15 | �й���ѧԺ���ݻ�ѧ�о��� | 可生物降解和/或可生物吸收纤维制品及其在医学领域的应用 |
| CN101094613A (zh) * | 2003-11-10 | 2007-12-26 | 血管技术国际股份公司 | 医用植入物和抗瘢痕形成剂 |
| CN104096272A (zh) * | 2013-04-03 | 2014-10-15 | 中国科学院化学研究所 | 用于手术后抗感染的复合静电纺丝纳米纤维膜疝修补片及其制备方法 |
| CN112043867A (zh) * | 2019-06-05 | 2020-12-08 | 四川大学 | 一种异构双层多孔胶原基骨缺损修复屏障膜及其制备方法 |
| CN113018261A (zh) * | 2021-03-15 | 2021-06-25 | 四川大学 | 一种具有多重释药功能的载药纳米胶束及其制备方法 |
| CN113577376A (zh) * | 2021-08-10 | 2021-11-02 | 四川大学 | 一种双重载药多糖基自愈合水凝胶及其制备方法 |
-
2022
- 2022-09-27 CN CN202211184186.1A patent/CN115475285A/zh active Pending
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1529653A (zh) * | 2001-05-16 | 2004-09-15 | �й���ѧԺ���ݻ�ѧ�о��� | 可生物降解和/或可生物吸收纤维制品及其在医学领域的应用 |
| CN101094613A (zh) * | 2003-11-10 | 2007-12-26 | 血管技术国际股份公司 | 医用植入物和抗瘢痕形成剂 |
| CN104096272A (zh) * | 2013-04-03 | 2014-10-15 | 中国科学院化学研究所 | 用于手术后抗感染的复合静电纺丝纳米纤维膜疝修补片及其制备方法 |
| CN112043867A (zh) * | 2019-06-05 | 2020-12-08 | 四川大学 | 一种异构双层多孔胶原基骨缺损修复屏障膜及其制备方法 |
| CN113018261A (zh) * | 2021-03-15 | 2021-06-25 | 四川大学 | 一种具有多重释药功能的载药纳米胶束及其制备方法 |
| CN113577376A (zh) * | 2021-08-10 | 2021-11-02 | 四川大学 | 一种双重载药多糖基自愈合水凝胶及其制备方法 |
Non-Patent Citations (2)
| Title |
|---|
| LIU XIAOCHEN: "One-step treatment of periodontitis based on a core-shell micelle-in-nanofiber membrane with time-programmed drug release", JOURNAL OF CONTROLLED RELEASE * |
| 刘肖晨: "负载不同胶束纳米纤维膜的构建及其体外抗炎作用比较研究", 口腔颌面外科杂志 * |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Chen et al. | Dynamic covalent constructed self-healing hydrogel for sequential delivery of antibacterial agent and growth factor in wound healing | |
| Taheri et al. | Physical, mechanical and wound healing properties of chitosan/gelatin blend films containing tannic acid and/or bacterial nanocellulose | |
| Rad et al. | Fabrication and characterization of PCL/zein/gum arabic electrospun nanocomposite scaffold for skin tissue engineering | |
| EP3317326B1 (fr) | Procédé de fabrication d'hydrogel à base de chitosan et de polyélectrolytes chargés négativement et matériau poreux alvéolaire issu dudit hydrogel | |
| Fonseca-Santos et al. | An overview of carboxymethyl derivatives of chitosan: Their use as biomaterials and drug delivery systems | |
| Ye et al. | Development of gelatin/bacterial cellulose composite sponges as potential natural wound dressings | |
| CA2625875C (en) | Encapsulation system | |
| Zhao et al. | In situ cross-linked polysaccharide hydrogel as extracellular matrix mimics for antibiotics delivery | |
| Batista et al. | Alginate: Pharmaceutical and medical applications | |
| Dwivedi et al. | Nanofibre based smart pharmaceutical scaffolds for wound repair and regenerations | |
| US20070248642A1 (en) | Foam and use thereof | |
| Wu et al. | Chitosan-based polyelectrolyte complex scaffolds with antibacterial properties for treating dental bone defects | |
| Habibi et al. | A bilayer mupirocin/bupivacaine-loaded wound dressing based on chitosan/poly (vinyl alcohol) nanofibrous mat: Preparation, characterization, and controlled drug release | |
| Chen et al. | Porous polydroxyalkanoates (PHA) scaffolds with antibacterial property for oral soft tissue regeneration | |
| Zafar et al. | Role of crosslinkers for synthesizing biocompatible, biodegradable and mechanically strong hydrogels with desired release profile | |
| Wei et al. | Polypropylene composite hernia mesh with anti-adhesion layer composed of PVA hydrogel and liposomes drug delivery system | |
| Manna et al. | Recent update on alginate based promising transdermal drug delivery systems | |
| Pang et al. | Gallic acid-grafted chitosan antibacterial hydrogel incorporated with polydopamine-modified hydroxyapatite for enhancing bone healing | |
| CN115475285A (zh) | 有梯度释药功能的双载药胶原基屏障膜及制备方法和应用 | |
| Prabu et al. | Antimicrobial drug release scaffolds of natural and synthetic biodegradable polymers | |
| Oh et al. | Photodynamic graphene oxide combined alginate hydrogel for controlled drug release | |
| Naghibzadeh | Nanofibers for Skin Regeneration. | |
| da Silveira et al. | Biopolymer membranes for dentistry applications | |
| Magagula et al. | Biopolymer-based biodegradable biomaterials for in vivo and in vitro biomedical applications | |
| Wang et al. | In vitro and in vivo studies of a collagen-based scaffold carrying PLGA microspheres for sustained release of epidermal growth factor in skin regeneration |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20221216 |