CN116687869B - 一种双载体的氟比洛芬酯纳米载药材料及其制备方法 - Google Patents
一种双载体的氟比洛芬酯纳米载药材料及其制备方法 Download PDFInfo
- Publication number
- CN116687869B CN116687869B CN202310678158.3A CN202310678158A CN116687869B CN 116687869 B CN116687869 B CN 116687869B CN 202310678158 A CN202310678158 A CN 202310678158A CN 116687869 B CN116687869 B CN 116687869B
- Authority
- CN
- China
- Prior art keywords
- flurbiprofen axetil
- carrier
- nano
- double
- solution
- 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.)
- Active
Links
- ALIVXCSEERJYHU-UHFFFAOYSA-N Flurbiprofen axetil Chemical compound FC1=CC(C(C)C(=O)OC(OC(C)=O)C)=CC=C1C1=CC=CC=C1 ALIVXCSEERJYHU-UHFFFAOYSA-N 0.000 title claims abstract description 85
- 229950005941 flurbiprofen axetil Drugs 0.000 title claims abstract description 85
- 239000000463 material Substances 0.000 title claims abstract description 68
- 238000002360 preparation method Methods 0.000 title claims abstract description 19
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 30
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims abstract description 24
- 238000003756 stirring Methods 0.000 claims abstract description 18
- 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 claims abstract description 14
- 229920002674 hyaluronan Polymers 0.000 claims abstract description 14
- 229960003160 hyaluronic acid Drugs 0.000 claims abstract description 14
- 239000004372 Polyvinyl alcohol Substances 0.000 claims abstract description 13
- 229920002451 polyvinyl alcohol Polymers 0.000 claims abstract description 13
- 229920001606 poly(lactic acid-co-glycolic acid) Polymers 0.000 claims abstract description 11
- 239000000843 powder Substances 0.000 claims abstract description 11
- 239000007787 solid Substances 0.000 claims abstract description 11
- IBVAQQYNSHJXBV-UHFFFAOYSA-N adipic acid dihydrazide Chemical compound NNC(=O)CCCCC(=O)NN IBVAQQYNSHJXBV-UHFFFAOYSA-N 0.000 claims abstract description 7
- 238000004108 freeze drying Methods 0.000 claims abstract description 6
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 claims abstract description 6
- 229920000053 polysorbate 80 Polymers 0.000 claims abstract description 6
- 238000005303 weighing Methods 0.000 claims abstract description 6
- 238000009210 therapy by ultrasound Methods 0.000 claims abstract description 5
- 239000003814 drug Substances 0.000 claims description 63
- 229940079593 drug Drugs 0.000 claims description 39
- 239000000243 solution Substances 0.000 claims description 33
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 19
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 14
- 238000011068 loading method Methods 0.000 claims description 14
- 239000011259 mixed solution Substances 0.000 claims description 14
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 12
- 239000000969 carrier Substances 0.000 claims description 12
- 238000000502 dialysis Methods 0.000 claims description 12
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims description 10
- 238000006243 chemical reaction Methods 0.000 claims description 10
- 230000009977 dual effect Effects 0.000 claims description 10
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 9
- 235000019441 ethanol Nutrition 0.000 claims description 8
- 238000000034 method Methods 0.000 claims description 8
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 6
- 229920001577 copolymer Polymers 0.000 claims description 5
- 239000008367 deionised water Substances 0.000 claims description 5
- 229910021641 deionized water Inorganic materials 0.000 claims description 5
- NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 claims description 4
- 239000011780 sodium chloride Substances 0.000 claims description 3
- JALUUBQFLPUJMY-UHFFFAOYSA-N 2-(4-phenylphenyl)propanoic acid Chemical compound C1=CC(C(C(O)=O)C)=CC=C1C1=CC=CC=C1 JALUUBQFLPUJMY-UHFFFAOYSA-N 0.000 claims description 2
- 229950003588 axetil Drugs 0.000 claims description 2
- 238000003287 bathing Methods 0.000 claims 1
- 230000000694 effects Effects 0.000 abstract description 11
- 239000002539 nanocarrier Substances 0.000 abstract description 9
- 231100000331 toxic Toxicity 0.000 abstract description 4
- 230000002588 toxic effect Effects 0.000 abstract description 4
- 238000012360 testing method Methods 0.000 description 21
- 210000004027 cell Anatomy 0.000 description 15
- 239000000523 sample Substances 0.000 description 14
- 239000002086 nanomaterial Substances 0.000 description 11
- 208000002193 Pain Diseases 0.000 description 7
- 230000036407 pain Effects 0.000 description 7
- 230000001988 toxicity Effects 0.000 description 7
- 231100000419 toxicity Toxicity 0.000 description 7
- 229960002390 flurbiprofen Drugs 0.000 description 6
- 230000005764 inhibitory process Effects 0.000 description 6
- 239000003607 modifier Substances 0.000 description 6
- 230000003013 cytotoxicity Effects 0.000 description 5
- 231100000135 cytotoxicity Toxicity 0.000 description 5
- 238000002474 experimental method Methods 0.000 description 5
- -1 flurbiprofen ester Chemical class 0.000 description 5
- 230000005012 migration Effects 0.000 description 5
- 238000013508 migration Methods 0.000 description 5
- 239000000203 mixture Substances 0.000 description 5
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 4
- 230000002401 inhibitory effect Effects 0.000 description 4
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 4
- 230000002829 reductive effect Effects 0.000 description 4
- IZTQOLKUZKXIRV-YRVFCXMDSA-N sincalide Chemical compound C([C@@H](C(=O)N[C@@H](CCSC)C(=O)NCC(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(N)=O)NC(=O)[C@@H](N)CC(O)=O)C1=CC=C(OS(O)(=O)=O)C=C1 IZTQOLKUZKXIRV-YRVFCXMDSA-N 0.000 description 4
- 238000003860 storage Methods 0.000 description 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 108010087230 Sincalide Proteins 0.000 description 3
- 230000009286 beneficial effect Effects 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 238000010609 cell counting kit-8 assay Methods 0.000 description 3
- 230000003833 cell viability Effects 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 231100000263 cytotoxicity test Toxicity 0.000 description 3
- 230000002900 effect on cell Effects 0.000 description 3
- SYTBZMRGLBWNTM-UHFFFAOYSA-N flurbiprofen Chemical compound FC1=CC(C(C(O)=O)C)=CC=C1C1=CC=CC=C1 SYTBZMRGLBWNTM-UHFFFAOYSA-N 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 239000002245 particle Substances 0.000 description 3
- 230000002195 synergetic effect Effects 0.000 description 3
- 206010067484 Adverse reaction Diseases 0.000 description 2
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 2
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 2
- 102000004005 Prostaglandin-endoperoxide synthases Human genes 0.000 description 2
- 108090000459 Prostaglandin-endoperoxide synthases Proteins 0.000 description 2
- 238000003917 TEM image Methods 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 230000006838 adverse reaction Effects 0.000 description 2
- 230000036592 analgesia Effects 0.000 description 2
- 239000012876 carrier material Substances 0.000 description 2
- 230000012292 cell migration Effects 0.000 description 2
- 229910052802 copper Inorganic materials 0.000 description 2
- 239000010949 copper Substances 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 238000007865 diluting Methods 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 239000000975 dye Substances 0.000 description 2
- 239000012535 impurity Substances 0.000 description 2
- 208000014674 injury Diseases 0.000 description 2
- 239000004310 lactic acid Substances 0.000 description 2
- 235000014655 lactic acid Nutrition 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 231100001083 no cytotoxicity Toxicity 0.000 description 2
- 238000007747 plating Methods 0.000 description 2
- 229920000642 polymer Polymers 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- 101800005151 Cholecystokinin-8 Proteins 0.000 description 1
- 102400000888 Cholecystokinin-8 Human genes 0.000 description 1
- 206010012735 Diarrhoea Diseases 0.000 description 1
- 208000010201 Exanthema Diseases 0.000 description 1
- 206010061459 Gastrointestinal ulcer Diseases 0.000 description 1
- 229920002683 Glycosaminoglycan Polymers 0.000 description 1
- 206010018999 Haemorrhage subcutaneous Diseases 0.000 description 1
- 208000032843 Hemorrhage Diseases 0.000 description 1
- 208000004454 Hyperalgesia Diseases 0.000 description 1
- 208000035154 Hyperesthesia Diseases 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 206010022067 Injection site haemorrhage Diseases 0.000 description 1
- 206010028813 Nausea Diseases 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 206010033557 Palpitations Diseases 0.000 description 1
- 208000003251 Pruritus Diseases 0.000 description 1
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 1
- 229910000831 Steel Inorganic materials 0.000 description 1
- 102000003929 Transaminases Human genes 0.000 description 1
- 108090000340 Transaminases Proteins 0.000 description 1
- COQLPRJCUIATTQ-UHFFFAOYSA-N Uranyl acetate Chemical compound O.O.O=[U]=O.CC(O)=O.CC(O)=O COQLPRJCUIATTQ-UHFFFAOYSA-N 0.000 description 1
- 206010047700 Vomiting Diseases 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 238000005299 abrasion Methods 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 239000012932 acetate dye Substances 0.000 description 1
- PQLVXDKIJBQVDF-UHFFFAOYSA-N acetic acid;hydrate Chemical compound O.CC(O)=O PQLVXDKIJBQVDF-UHFFFAOYSA-N 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 230000001070 adhesive effect Effects 0.000 description 1
- 230000003444 anaesthetic effect Effects 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 239000012620 biological material Substances 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 238000001516 cell proliferation assay Methods 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 239000000084 colloidal system Substances 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 239000007857 degradation product Substances 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 238000009792 diffusion process Methods 0.000 description 1
- 210000002249 digestive system Anatomy 0.000 description 1
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 238000004043 dyeing Methods 0.000 description 1
- 239000003792 electrolyte Substances 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 201000005884 exanthem Diseases 0.000 description 1
- 210000002744 extracellular matrix Anatomy 0.000 description 1
- 238000001506 fluorescence spectroscopy Methods 0.000 description 1
- 229920001002 functional polymer Polymers 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
- 229910052737 gold Inorganic materials 0.000 description 1
- 239000010931 gold Substances 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 230000007803 itching Effects 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 239000007791 liquid phase Substances 0.000 description 1
- 230000001050 lubricating effect Effects 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 238000005374 membrane filtration Methods 0.000 description 1
- 230000037353 metabolic pathway Effects 0.000 description 1
- 238000001000 micrograph Methods 0.000 description 1
- 239000004005 microsphere Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- 229910000403 monosodium phosphate Inorganic materials 0.000 description 1
- 235000019799 monosodium phosphate Nutrition 0.000 description 1
- 239000002103 nanocoating Substances 0.000 description 1
- 239000002114 nanocomposite Substances 0.000 description 1
- 230000008693 nausea Effects 0.000 description 1
- 231100000956 nontoxicity Toxicity 0.000 description 1
- 229960002378 oftasceine Drugs 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 229940094443 oxytocics prostaglandins Drugs 0.000 description 1
- 239000003973 paint Substances 0.000 description 1
- 239000000123 paper Substances 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 230000002980 postoperative effect Effects 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 150000003180 prostaglandins Chemical class 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 206010037844 rash Diseases 0.000 description 1
- 239000013558 reference substance Substances 0.000 description 1
- 230000000630 rising effect Effects 0.000 description 1
- 238000005464 sample preparation method Methods 0.000 description 1
- 239000012488 sample solution Substances 0.000 description 1
- 238000001878 scanning electron micrograph Methods 0.000 description 1
- 229910052710 silicon Inorganic materials 0.000 description 1
- 239000010703 silicon Substances 0.000 description 1
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 1
- 210000000278 spinal cord Anatomy 0.000 description 1
- 238000005507 spraying Methods 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 239000010959 steel Substances 0.000 description 1
- 230000003637 steroidlike Effects 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 239000004753 textile Substances 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- 230000008673 vomiting Effects 0.000 description 1
- 239000002023 wood Substances 0.000 description 1
- 230000029663 wound healing Effects 0.000 description 1
- 238000000733 zeta-potential measurement Methods 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/19—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles lyophilised, i.e. freeze-dried, solutions or dispersions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
- A61K31/22—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
- A61K31/222—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin with compounds having aromatic groups, e.g. dipivefrine, ibopamine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/34—Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Epidemiology (AREA)
- Inorganic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Emergency Medicine (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
本发明公开了一种双载体的氟比洛芬酯纳米载药材料及其制备方法,按以下步骤进行制备:S1:用己二酸二酰肼对透明质酸进行化学修饰,制备固体粉末HA‑ADH;S2:制备HA‑PLGA;S3:制备双载体的氟比洛芬酯纳米载药材料:称取氟比洛芬酯溶于无水乙醇中,再加入步骤S2制得的HA‑PLGA、吐温80和二氯甲烷搅拌20min;再加入l1.5wt%的聚乙烯醇溶液,冰浴,200W超声20min后继续搅拌8h,透析后冻干得到双载体的氟比洛芬酯纳米载药材料,为固体粉末状。本发明制得的双载体的氟比洛芬酯纳米载药材料具备良好的稳定性,且毒副作用较低。
Description
技术领域
本发明涉及纳米复合材料技术领域,特别涉及一种双载体的氟比洛芬酯纳米载药材料及其制备方法。
背景技术
氟比洛芬酯(Flurbiprofen axetil),是氟比洛芬的前体药物,用于手术后及各种癌症的镇痛。氟比洛芬酯注射液是一种非甾体类靶向镇痛药,通过在脊髓和外周抑制环氧化酶(COX)减少前列腺素的合成,降低手术创伤引起的痛觉过敏状态。脂微球制剂药效更强,起效更迅速,持续时间更长,且不易引起胃黏膜损伤等不良反应。其用于术后镇痛,优点在于没有中枢抑制作用,不影响处于麻醉状态患者的苏醒,可在术后立即使用。
现有的氟比洛芬酯在应用时,受到存储条件的影响,稳定性和安全性无法得到保证。由于氟比洛芬酯为酯类化合物,在存放过程中易水解生成杂质氟比洛芬,从而导致有效成分含量降低,杂质含量上升,影响其有效性和安全性。另外,氟比洛芬酯注射液在使用中存在一些难以避免的毒副作用,且不良反应发生几率较大,如:注射部位疼痛及皮下出血;循环系统血压上升、心悸;皮肤偶见瘙痒、皮疹等过敏反应;消化系统出现恶心呕吐、转氨酶升高、腹泻、胃肠道溃疡出血等,这是氟比洛芬酯类药物亟需改进的一大问题。
聚乳酸-羟基乙酸共聚物(poly(lactic-co-glycolic acid),PLGA)由两种单体--乳酸和羟基乙酸随机聚合而成,是一种可降解的功能高分子有机化合物,具有良好的生物相容性、无毒、良好的成囊和成膜的性能,被广泛应用于制药、医用工程材料和现代化工业领域。PLGA的降解产物是乳酸和羟基乙酸,同时也是人代谢途径的副产物,所以当它应用在医药和生物材料中时不会有毒副作用。
透明质酸(HA)是细胞外基质中广泛存在的蛋白多糖成分,具有良好的生物相容性,有望成为理想的缓释、控释药物载体材料。透明质酸是一种酸性粘多糖,以其独特的分子结构和理化性质在机体内显示出多种重要的生理功能,如润滑关节,调节血管壁的通透性,调节蛋白质,水电解质扩散及运转,促进创伤愈合等。
聚乙烯醇(PVA)是一种用途相当广泛的水溶性高分子聚合物。PVA具有独特的强力粘接性、皮膜柔韧性、平滑性、耐油性、耐溶剂性、保护胶体性、气体阻绝性、而磨性以及经特殊处理具有的耐水性,还被大量用于生产涂料、粘合剂、纸品加工剂、乳化剂、分散剂薄膜等产品。应用范围遍及纺织、食品、医药、建筑、木材加工、造纸、印刷、农业、钢铁、高分子化工等行业。
发明内容
为了克服现有技术的不足,本发明目的是提供一种双载体的氟比洛芬酯纳米载药材料的制备方法,该制备方法工艺简单,且制得的双载体的氟比洛芬酯纳米载药材料相比氟比洛芬酯原药毒副作用较低。
为了达到上述目的,本发明采用以下技术方案:
本发明提供一种双载体的氟比洛芬酯纳米载药材料的制备方法,包括以下步骤:
S1:用己二酸二酰肼对透明质酸进行化学修饰,制备固体粉末HA-ADH;
S2:制备HA-PLGA:将聚乳酸-羟基乙酸共聚物溶于二甲基亚砜、1,2-二氯乙烷和N-羟基丁二酰亚胺的混合溶液中充分搅拌,然后加入步骤S1制得的HA-ADH搅拌12h,待反应停止后透析得到HA-PLGA;
S3:制备双载体的氟比洛芬酯纳米载药材料:称取氟比洛芬酯溶于无水乙醇中,再加入步骤S2制得的HA-PLGA、吐温80和二氯甲烷搅拌20min;再加入l1.5wt%的聚乙烯醇溶液,冰浴,200W超声20min后继续搅拌8h,透析后冻干得到双载体的氟比洛芬酯纳米载药材料,为固体粉末状。
相比于现有技术,本发明通过制备双载体的纳米包载材料对氟比洛芬酯进行包覆,提高了氟比洛芬酯的稳定性,且制得的双载体的氟比洛芬酯纳米载药材料在细胞实验、迁移实验和荧光实验中均表现出较低的毒性,使其应用范围有望得到拓展。
进一步地,步骤S1包括以下步骤:
S11:称取透明质酸溶解于去离子水中,再加入己二酸二酰肼在室温下搅拌10min;
S12:待反应停止后,用50%的盐酸溶液调节混合溶液pH值至4.8,再加入乙醇溶液混合搅拌10min;
S13:称取1,2-二氯乙烷加入混合溶液中,并通过50%的盐酸溶液保持混合溶液pH值为4.8,反应2h;反应停止之后用20%的NaOH溶液将混合溶液pH值提升至7;
S14:将混合溶液透析后冻干得到固体粉末HA-ADH。
优选地,步骤S1中,透明质酸、去离子水、己二酸二酰肼、乙醇溶液、1,2-二氯乙烷的用量比为100mg:20mL:10mmol:20mL:1mmol。
优选地,步骤S2中,聚乳酸-羟基乙酸共聚物、二甲基亚砜、1,2-二氯乙烷、N-羟基丁二酰亚胺和HA-ADH的用量比为200mg:5mL:15μm:15μm:5mg;步骤S3中,氟比洛芬酯、无水乙醇、吐温80、二氯甲烷和聚乙烯醇溶液的用量比为200g:10mL:11.3μL:6.25mL:33mL。
优选地,各个步骤中的搅拌速度均为300r/min。
优选地,步骤S14中,透析步骤为:采用截留分子量为7000的透析带透析3天,第一天采用100mM的NaCl溶液透析,第二天采用体积百分比浓度为25%的乙醇溶液透析,第三天采用纯水透析。
优选地,步骤S2和步骤S3的透析均采用截留分子量为7000的透析带纯水透析3天。
本发明还提供如上所述制备方法制备得到的双载体的氟比洛芬酯纳米载药材料。
进一步地,所述双载体的氟比洛芬酯纳米载药材料载药率为33.86%。
与现有技术相比,本发明具有以下有益效果:通过PLGA和HA双载体,并以PVA作为修饰物,使制得的双载体的氟比洛芬酯纳米载药材料具备良好的稳定性,对储存条件要求较低;同时由于双载体和修饰物材料的协同作用,氟比洛芬酯纳米载药材料的毒性相比于氟比洛芬酯纯药也大幅降低,对患者更为友好,在镇痛的同时不会增加更多的痛苦和风险,也有利于氟比洛芬酯应用范围的拓展。
附图说明
图1为本发明的双载体的氟比洛芬酯纳米载药材料合成原理示意图;
图2为实施例1制得的双载体的氟比洛芬酯纳米载药材料的TEM图;
图3为实施例1制得的双载体的氟比洛芬酯纳米载药材料的SEM图;
图4为实施例1制得的双载体的氟比洛芬酯纳米载药材料的电位曲线图;
图5为测试例2的细胞毒性实验空载组测试结果柱状图;
图6为测试例2的细胞毒性实验材料组测试结果柱状图;
图7为测试例2的细胞毒性实验纯药组测试结果柱状图;
图8为测试例3得到的荧光图;
图9为测试例4得到的迁移实验显微镜图像;
图10为测试例4得到的迁移实验数据柱状图。
以下结合附图与具体实施例对本发明作进一步说明。
具体实施方式
以下实施例所用到的原料及试剂来源信息如表1所示:
表1原料及试剂来源
下面通过具体实施例以及附图对本发明作进一步阐释,但是本发明的技术方案不以具体实施例为限。
实施例1氟比洛芬酯纳米载药材料的制备
S1:制备固体粉末HA-ADH:称量100mgHA于50ml烧杯中,加入去离子水20mL使其完全溶解,再加入10mmolADH在室温300r/min的速度下搅拌10min。停止反应后用50%盐酸调节pH至4.8,再加入20ml乙醇(50%v/v)混合搅拌30min。称量1mmolEDC直接加入溶液,并通过加入盐酸保持和pH为4.8,反应2h。反应停之后用20%NaOH将溶液PH提升至7。反应溶液用透析带(MWCO为7000)透析3天,第一天100mM NaCl溶液,第二天25%(v/v)乙醇溶液,第三天纯水透析。再将溶液-80℃冷冻干燥得固体粉末HA-ADH。
S2:制备HA-PLGA:称量200mgPLGA于100mL烧杯中,加入5mlDMSO,15umolEDC和15umolNHS充分搅拌,溶液中加入5mgHA-ADH搅拌12h,反应停之后,溶液用透析带(MWCO为7000)纯水透析3天,得到HA-PLGA。
S3:制备氟比洛芬酯纳米载药材料:称量200mg氟比洛芬酯于100ml烧杯中,10mL无水乙醇使其完全溶解,再加入HA-PLGA,11.3μL吐温80和6.25mL二氯甲烷(DCM)搅拌20min。再加入33ml1.5wt%PVA溶液,冰浴200w超声20min,后继续搅拌过夜。7000Mv纯水透析,-80℃冷冻干燥得固体粉末。
请参阅图1,本发明采用PLGA和HA作为双载体,并采用PVA作为修饰物,使制得的双载体的氟比洛芬酯纳米载药材料具备良好的稳定性。同时由于双载体和修饰物材料的协同作用,氟比洛芬酯纳米载药材料的毒性相比于氟比洛芬酯纯药也大幅降低,对患者更为友好,在镇痛的同时不会增加患者更多的痛苦和风险,也有利于氟比洛芬酯应用范围的拓展。
测试例1双载体的氟比洛芬酯纳米载药材料的表征
采用负染制样方法对实施例1制得的双载体的氟比洛芬酯纳米载药材料进行制样并在透射电子显微镜下观察:将样品稀释至1mg/mL,取10uL滴于铜网上静置10min后吸走多余样品,再滴10uL醋酸双氧铀染液滴于原铜网,静置1min后吸走多余染液,晾干即可上镜观察。
请参阅图2,其为实施例1制得的双载体的氟比洛芬酯纳米载药材料的TEM图。从图中可以看出,制得的双载体的氟比洛芬酯纳米载药材料颗粒均匀,分散度好,粒径约为300nm,达到纳米载药材料标准。
ZETA电位测定:取约1mg样品,置于5mL离心管中,加入2mL水,超声分散5min。取1mL上层溶液,缓慢加入样品池中,避免样品池内出现气泡。采用马尔文激光粒度仪ZS90进行测试,仪器预热30min;启动测试软件,选择Zeta测试程序,选择水为溶剂,25℃下预热30s后测定,每个样品平行测定3次。
请参阅图3,经测定,实施例1制得的双载体的氟比洛芬酯纳米载药材料电位均值为-30.6mV,处于相对稳定的区间内,且主要带负电。可见制得的双载体的氟比洛芬酯纳米载药材料稳定性较好,且与细胞结合效果良好。
扫描电镜观察:将冷藏保存的样品取出,超声10min后滴在硅片上自然干燥,干燥后粘贴在样品台后喷金,最后进电镜观察。
请参阅图4,可以观察到在扫描电镜下,实施例1制得的双载体的氟比洛芬酯纳米载药材料形态大致为棒状。
测试例2双载体的氟比洛芬酯纳米载药材料对HaCaT细胞的毒性测定
采用CCK-8检测增殖法,使用细胞计数试剂盒(CCK-8;美仑)测定双载体的氟比洛芬酯纳米载药材料,先取100微升细胞悬液(5X104细胞/毫升;Hacat细胞的来源:尚恩生物,货号:SNL-163,细胞培养方法:10%FBS+DMEM(货号:MA0212-Dec-28H))接种于96孔板,分别加入3种药物:第1组空载组(即PLGA+HA+PVA):不同浓度的空载;第2组纳米材料组:不同浓度的PLGA+HA+PVA+氟比洛芬酯;第3组纯药组:不同浓度的氟比洛芬酯;其中,空载组浓度与纳米材料组一致,纳米材料组和纯药组浓度以含氟比洛芬酯量计算,即相同浓度下的纳米材料组和纯药组是指二者含氟比洛芬酯的量相同。在37℃条件下分别培养24h、48h、72h,然后每孔加入CCK-8试剂(10微升),得到的混合物在37℃条件下培养50分钟。记录混合物在450nm处的吸光度并计数细胞活力。
结果如图5~7所示,可以看出,空载组对HaCaT细胞几乎无抑制作用,24h时250~500ug/ml的浓度和72h时125~500ug/ml的浓度的纳米材料组的对细胞抑制作用强于空载组,但对细胞均无明显抑制作用;而24h时62~500ug/ml的浓度的纯药对细胞的抑制作用强于空载组和材料组,且对细胞有明显抑制作用。可见,24h和72h时空载组和纳米材料组均几乎无细胞毒性,而纯药组在24h时有明显细胞毒性,72h时则几乎无细胞毒性,原因可能是氟比洛芬酯纯药在24小时左右就完成分解了。综合三组的情况可以看出,双载体的氟比洛芬酯纳米载药材料相比氟比洛芬酯对HaCaT细胞的毒性更为微弱,安全性较强;且其作用时间相比氟比洛芬酯纯药较长,具备一定的缓释性能。
测试例3双载体的氟比洛芬酯纳米载药材料对HaCaT细胞的荧光测试
采用以下步骤进行荧光测试:
第一天,铺板:6孔板20万个/孔,HaCaT;
第二天,给药:分组:①空白组;②纳米材料组:PLGA+HA+PVA+氟比洛芬酯;浓度:139.2μg/mL;③纯药组:氟比洛芬酯;浓度:47.13μg/mL
第三天,分别用PI、AM染色观察荧光:(1)吸去培养基;(2)PBS洗2-3次;(3)加入染液15min;(4)PBS洗2-3次;(5)观察拍照。试剂盒为碧云天-Calcein/PI细胞活性与细胞毒性检测试剂盒(货号:MA0361)。
如图8所示,空白组与材料组细胞存活率无显著性差异;而纯药组相比空白组和材料组细胞存活率较低,表明该纳米材料在139.2μg/mL浓度下细胞毒性不强,而氟比洛芬酯纯药则有较强的细胞毒性。
测试例4双载体的氟比洛芬酯纳米载药材料对HaCaT细胞的迁移实验
进一步采用以下方法进行迁移实验:具体步骤为:
第一天铺板:6孔板30万/孔,HaCaT;
第二天:加药:
分组:
①空白组:DMEM;
②纳米材料组:PLGA+HA+PVA+氟比洛芬酯
浓度:139.2μg/mL(浓度选择是按照CCK8数据作散点图,根据回归线方程选取细胞活力百分之80时的给药浓度,请参阅图6);
③纯药组:氟比洛芬酯
浓度:47.13μg/mL(浓度选择是根据纳米药物给药浓度的氟比洛芬酯载药量(请参阅测试例5,载药率为33.86%),使纯药组和材料组含氟比洛芬酯的量一致)。
结果如图9和图10所示,可以看出,该浓度下材料组抑制细胞迁移效果不明显,而纯药组抑制细胞迁移较明显。可见,相比于氟比洛芬酯纯药,双载体的氟比洛芬酯纳米载药材料对HaCaT细胞的抑制作用较弱,毒性较低,安全性较高。
测试例5双载体的氟比洛芬酯纳米载药材料载药率测试
采用高效液相法对实施例1制得的氟比洛芬酯纳米载药材料进行载药率测试,实验条件为:
仪器:岛津LC-20AD
色谱柱:Ultimate Plus-C18 4.6*150mm 5um
磷酸缓冲液:1mol/L磷酸二氢钠溶液1.3ml与0.5mol/L磷酸氢二钠32.5ml,用水稀释至1000ml,调PH=8.00
流动相:乙腈-0.3%乙酸水=65-35
流速:1.0ml/min
柱温:30
检测波长:254nm
进样量:5uL
样品配置:
对照溶液:精密称取对照品(氟比洛芬酯纯药)适量,加DMSO溶解稀释至各浓度(20,40,60,80,100ug/ml)
样品溶液:精密称取实施例1制得的双载体的氟比洛芬酯纳米载药材料2.0mg,加1.0ml二氯甲烷,超声30min,精密移取200ul上述溶液,加800ul甲醇,摇匀,过膜,即得。
表2载药率测试数据表
经过测试,如表2所示,双载体的氟比洛芬酯纳米载药材料的载药率为33.86%,达到较高水平。
相比于现有技术,本发明通过采用PLGA和HA双载体,并采用PVA作为修饰物,对氟比洛芬酯进行包覆,使制得的双载体的氟比洛芬酯纳米载药材料具备良好的稳定性,对储存条件的要求较低。同时由于双载体和修饰物材料的协同作用,氟比洛芬酯纳米载药材料的毒性相比于氟比洛芬酯纯药也有明显降低,对患者更为友好,在镇痛的同时不会增加更多的痛苦和风险,也有利于氟比洛芬酯应用范围的拓展。此外,在细胞毒性实验中还可以看出制得的双载体的氟比洛芬酯纳米载药材料具有一定的缓释性能,这也为其进一步拓宽应用范围提供了可能性。
本发明并不局限于上述实施方式,如果对本发明的各种改动或变型不脱离本发明的精神和范围,倘若这些改动和变型属于本发明的权利要求和等同技术范围之内,则本发明也意图包含这些改动和变动。
Claims (6)
1.一种双载体的氟比洛芬酯纳米载药材料的制备方法,其特征在于,包括以下步骤:
S1:用己二酸二酰肼对透明质酸进行化学修饰,制备固体粉末HA-ADH;
S2:制备HA-PLGA:将聚乳酸-羟基乙酸共聚物溶于二甲基亚砜、1,2-二氯乙烷和N-羟基丁二酰亚胺的混合溶液中充分搅拌,然后加入步骤S1制得的HA-ADH搅拌12h,待反应停止后透析得到HA-PLGA;
S3:制备双载体的氟比洛芬酯纳米载药材料:称取氟比洛芬酯溶于无水乙醇中,再加入步骤S2制得的HA-PLGA、吐温80和二氯甲烷搅拌20min;再加入1.5wt%的聚乙烯醇溶液,冰浴,200W超声20min后继续搅拌8h,透析后冻干得到双载体的氟比洛芬酯纳米载药材料,为固体粉末状;
步骤S1包括以下步骤:
S11:称取透明质酸溶解于去离子水中,再加入己二酸二酰肼在室温下搅拌10min;
S12:待反应停止后,用50%的盐酸溶液调节混合溶液pH值至4.8,再加入乙醇溶液混合搅拌10min;
S13:称取1,2-二氯乙烷加入混合溶液中,并通过50%的盐酸溶液保持混合溶液pH值为4.8,反应2h;反应停止之后用20%的NaOH溶液将混合溶液pH值提升至7;
S14:将混合溶液透析后冻干得到固体粉末HA-ADH;
步骤S1中,透明质酸、去离子水、己二酸二酰肼、乙醇溶液、1,2-二氯乙烷的用量比为100mg:20mL:10mmol:20mL:1mmol;
步骤S2中,聚乳酸-羟基乙酸共聚物、二甲基亚砜、1,2-二氯乙烷、N-羟基丁二酰亚胺和HA-ADH的用量比为200mg:5mL:15μmol:15μmol:5mg;步骤S3中,氟比洛芬酯、无水乙醇、吐温80、二氯甲烷和聚乙烯醇溶液的用量比为200mg:10mL: 11.3μL:6.25 mL: 33mL。
2.根据权利要求1所述的双载体的氟比洛芬酯纳米载药材料的制备方法,其特征在于:搅拌速度均为300r/min。
3.根据权利要求1所述的双载体的氟比洛芬酯纳米载药材料的制备方法,其特征在于:步骤S14中,透析步骤为:采用截留分子量为7000的透析袋透析3天,第一天采用100mM的NaCl溶液透析,第二天采用体积百分比浓度为25%的乙醇溶液透析,第三天采用纯水透析。
4.根据权利要求1所述的双载体的氟比洛芬酯纳米载药材料的制备方法,其特征在于:步骤S2和步骤S3的透析均采用截留分子量为7000的透析袋纯水透析3天。
5.一种根据权利要求1~4任一项所述的制备方法制得的双载体的氟比洛芬酯纳米载药材料。
6.根据权利要求5所述双载体的氟比洛芬酯纳米载药材料,其特征在于:所述双载体的氟比洛芬酯纳米载药材料载药率为33.86%。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202310678158.3A CN116687869B (zh) | 2023-06-08 | 2023-06-08 | 一种双载体的氟比洛芬酯纳米载药材料及其制备方法 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202310678158.3A CN116687869B (zh) | 2023-06-08 | 2023-06-08 | 一种双载体的氟比洛芬酯纳米载药材料及其制备方法 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN116687869A CN116687869A (zh) | 2023-09-05 |
CN116687869B true CN116687869B (zh) | 2024-03-22 |
Family
ID=87825185
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202310678158.3A Active CN116687869B (zh) | 2023-06-08 | 2023-06-08 | 一种双载体的氟比洛芬酯纳米载药材料及其制备方法 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN116687869B (zh) |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN116585488B (zh) * | 2023-05-08 | 2024-02-23 | 广东省第二人民医院(广东省卫生应急医院) | 一种罗哌卡因纳米载药材料及其制备方法 |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH11222425A (ja) * | 1997-10-27 | 1999-08-17 | Ss Pharmaceut Co Ltd | 関節疾患治療用関節内投与製剤 |
CN102911380A (zh) * | 2012-10-29 | 2013-02-06 | 北京爱美客生物科技有限公司 | 透明质酸与生物可降解高分子改性材料及制备方法 |
CN113795246A (zh) * | 2019-05-06 | 2021-12-14 | 福多兹制药公司 | 用于治疗关节疼痛和炎症的可注射缓释制剂 |
-
2023
- 2023-06-08 CN CN202310678158.3A patent/CN116687869B/zh active Active
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH11222425A (ja) * | 1997-10-27 | 1999-08-17 | Ss Pharmaceut Co Ltd | 関節疾患治療用関節内投与製剤 |
CN102911380A (zh) * | 2012-10-29 | 2013-02-06 | 北京爱美客生物科技有限公司 | 透明质酸与生物可降解高分子改性材料及制备方法 |
CN113795246A (zh) * | 2019-05-06 | 2021-12-14 | 福多兹制药公司 | 用于治疗关节疼痛和炎症的可注射缓释制剂 |
Non-Patent Citations (1)
Title |
---|
Guided bone regeneration by poly(lactic-co-glycolic acid) grafted hyaluronic acid bi-layer films for periodontal barrier applications;Park, JK等;《ACTA BIOMATERIALIA》;第5卷(第9期);3394-3403 * |
Also Published As
Publication number | Publication date |
---|---|
CN116687869A (zh) | 2023-09-05 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
TWI306869B (en) | Amphiphilic block copolymers and nano particles comprising the same | |
CN116687869B (zh) | 一种双载体的氟比洛芬酯纳米载药材料及其制备方法 | |
Wang et al. | Preparation and pH controlled release of polyelectrolyte complex of poly (l-malic acid-co-d, l-lactic acid) and chitosan | |
US9283190B2 (en) | Highly efficient and long-acting slow-release formulation of poorly soluble drugs and preparation method thereof | |
US20100254939A1 (en) | Graft copolymers as drug delivery systems | |
CN113197843A (zh) | 一种多巴胺涂覆的纤维素纳米晶-琼脂糖载药水凝胶及其制备方法 | |
CN111407740A (zh) | 一种超声可激活释放药物的白蛋白纳米粒子、其制备方法及应用 | |
Liang et al. | 5-Fluorouracil-loaded self-assembled pH-sensitive nanoparticles as novel drug carrier for treatment of malignant tumors | |
CN111763315A (zh) | 一种新型聚酯化合物与其为载体的纳米药物及该药物的应用 | |
CN108503718B (zh) | 一种羟烷基淀粉偶联物及其制备方法和应用 | |
CN110585136A (zh) | 一种负载蛋白多肽的生物素修饰三甲基壳聚糖纳米粒及其制备方法 | |
CN107049950B (zh) | 一种环糊精聚合物载药囊泡的制备方法 | |
US11191728B2 (en) | Method of preparing degradable and environment responsive composite microgels | |
Sarkar et al. | Modified alginates in drug delivery | |
CN115969992A (zh) | 一种用于重塑肿瘤免疫微环境的苯硼酸共聚物及其应用 | |
Karimi et al. | Amphotericin-B and vancomycin-loaded chitosan nanofiber for antifungal and antibacterial application | |
Chan et al. | Regulation of particle morphology of pH-dependent poly (ε-caprolactone)-poly (γ-glutamic acid) micellar nanoparticles to combat breast cancer cells | |
CN112807443B (zh) | 一种多重协同的抗菌纳米前药 | |
US11623968B2 (en) | Method for preparation of xanthan gum copolymer nanomicelles | |
CN114524932A (zh) | 双亲性三嵌段聚氨基酸共聚物、中间体、制备及应用 | |
Lee et al. | Biomaterials Science | |
Movaffagh et al. | Preparation and in vitro evaluation of injectable formulations of levothyroxine sodium using in situ forming hydrogel temperature-responsive systems based on PLA-PEG-PLA and PLGA-PEG-PLGA triblock copolymers | |
WO2020088306A1 (zh) | 一种用于胰岛素口服递送的聚电解质复合物 | |
Zhou et al. | Fabrication and in vitro drug release study of microsphere drug delivery systems based on amphiphilic poly-α, β-[N-(2-hydroxyethyl)-l-aspartamide]-g-poly (l-lactide) graft copolymers | |
CN108434120B (zh) | 一种口服胰岛素纳米颗粒及其制备方法 |
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 | ||
GR01 | Patent grant | ||
GR01 | Patent grant |