CN109223712A - 氟比洛芬酯注射用乳剂及其制备方法 - Google Patents
氟比洛芬酯注射用乳剂及其制备方法 Download PDFInfo
- Publication number
- CN109223712A CN109223712A CN201811175197.7A CN201811175197A CN109223712A CN 109223712 A CN109223712 A CN 109223712A CN 201811175197 A CN201811175197 A CN 201811175197A CN 109223712 A CN109223712 A CN 109223712A
- Authority
- CN
- China
- Prior art keywords
- shear
- injection
- phase
- mixed
- preparation
- 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.)
- Granted
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 76
- 229950005941 flurbiprofen axetil Drugs 0.000 title claims abstract description 76
- 239000000839 emulsion Substances 0.000 title claims abstract description 69
- 238000002347 injection Methods 0.000 title claims abstract description 67
- 239000007924 injection Substances 0.000 title claims abstract description 67
- 238000002360 preparation method Methods 0.000 title claims abstract description 35
- 239000006071 cream Substances 0.000 claims abstract description 63
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 59
- 210000003022 colostrum Anatomy 0.000 claims abstract description 36
- 235000021277 colostrum Nutrition 0.000 claims abstract description 36
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 34
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 17
- 239000003381 stabilizer Substances 0.000 claims abstract description 15
- 239000008215 water for injection Substances 0.000 claims abstract description 14
- 230000003204 osmotic effect Effects 0.000 claims abstract description 12
- 239000003995 emulsifying agent Substances 0.000 claims abstract description 10
- 239000002904 solvent Substances 0.000 claims abstract description 9
- 239000003921 oil Substances 0.000 claims description 75
- 235000019198 oils Nutrition 0.000 claims description 75
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 24
- 239000011265 semifinished product Substances 0.000 claims description 14
- 230000001954 sterilising effect Effects 0.000 claims description 13
- 239000003549 soybean oil Substances 0.000 claims description 12
- 235000012424 soybean oil Nutrition 0.000 claims description 12
- 238000011049 filling Methods 0.000 claims description 10
- 238000007789 sealing Methods 0.000 claims description 10
- JQWAHKMIYCERGA-UHFFFAOYSA-N (2-nonanoyloxy-3-octadeca-9,12-dienoyloxypropoxy)-[2-(trimethylazaniumyl)ethyl]phosphinate Chemical group CCCCCCCCC(=O)OC(COP([O-])(=O)CC[N+](C)(C)C)COC(=O)CCCCCCCC=CCC=CCCCCC JQWAHKMIYCERGA-UHFFFAOYSA-N 0.000 claims description 9
- ZWZWYGMENQVNFU-UHFFFAOYSA-N Glycerophosphorylserin Natural products OC(=O)C(N)COP(O)(=O)OCC(O)CO ZWZWYGMENQVNFU-UHFFFAOYSA-N 0.000 claims description 6
- JLPULHDHAOZNQI-ZTIMHPMXSA-N 1-hexadecanoyl-2-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCC\C=C/C\C=C/CCCCC JLPULHDHAOZNQI-ZTIMHPMXSA-N 0.000 claims description 5
- 229940083466 soybean lecithin Drugs 0.000 claims description 5
- LRYZPFWEZHSTHD-HEFFAWAOSA-O 2-[[(e,2s,3r)-2-formamido-3-hydroxyoctadec-4-enoxy]-hydroxyphosphoryl]oxyethyl-trimethylazanium Chemical class CCCCCCCCCCCCC\C=C\[C@@H](O)[C@@H](NC=O)COP(O)(=O)OCC[N+](C)(C)C LRYZPFWEZHSTHD-HEFFAWAOSA-O 0.000 claims description 4
- 235000021355 Stearic acid Nutrition 0.000 claims description 4
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 claims description 4
- 229930006000 Sucrose Natural products 0.000 claims description 4
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 claims description 4
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 claims description 4
- 239000004006 olive oil Substances 0.000 claims description 4
- 235000008390 olive oil Nutrition 0.000 claims description 4
- 239000008117 stearic acid Substances 0.000 claims description 4
- 239000005720 sucrose Substances 0.000 claims description 4
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 claims description 4
- PORPENFLTBBHSG-MGBGTMOVSA-N 1,2-dihexadecanoyl-sn-glycerol-3-phosphate Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP(O)(O)=O)OC(=O)CCCCCCCCCCCCCCC PORPENFLTBBHSG-MGBGTMOVSA-N 0.000 claims description 3
- OIQOAYVCKAHSEJ-UHFFFAOYSA-N 2-[2,3-bis(2-hydroxyethoxy)propoxy]ethanol;hexadecanoic acid;octadecanoic acid Chemical compound OCCOCC(OCCO)COCCO.CCCCCCCCCCCCCCCC(O)=O.CCCCCCCCCCCCCCCCCC(O)=O OIQOAYVCKAHSEJ-UHFFFAOYSA-N 0.000 claims description 3
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 claims description 3
- 229930195725 Mannitol Natural products 0.000 claims description 3
- 239000002253 acid Substances 0.000 claims description 3
- 239000004615 ingredient Substances 0.000 claims description 3
- 239000000594 mannitol Substances 0.000 claims description 3
- 235000010355 mannitol Nutrition 0.000 claims description 3
- 239000002609 medium Substances 0.000 claims description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims 2
- TZCPCKNHXULUIY-RGULYWFUSA-N 1,2-distearoyl-sn-glycero-3-phosphoserine Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@H](COP(O)(=O)OC[C@H](N)C(O)=O)OC(=O)CCCCCCCCCCCCCCCCC TZCPCKNHXULUIY-RGULYWFUSA-N 0.000 claims 1
- 229910021529 ammonia Inorganic materials 0.000 claims 1
- 125000001095 phosphatidyl group Chemical group 0.000 claims 1
- 239000003814 drug Substances 0.000 abstract description 21
- 229940079593 drug Drugs 0.000 abstract description 20
- 230000001804 emulsifying effect Effects 0.000 abstract description 9
- 230000008685 targeting Effects 0.000 abstract description 9
- 238000005538 encapsulation Methods 0.000 abstract description 6
- 238000005516 engineering process Methods 0.000 abstract description 5
- 238000007667 floating Methods 0.000 description 29
- 230000000052 comparative effect Effects 0.000 description 28
- 238000009826 distribution Methods 0.000 description 18
- 238000000034 method Methods 0.000 description 16
- 239000000047 product Substances 0.000 description 15
- 239000002245 particle Substances 0.000 description 12
- 239000000243 solution Substances 0.000 description 12
- 235000013336 milk Nutrition 0.000 description 10
- 239000008267 milk Substances 0.000 description 10
- 210000004080 milk Anatomy 0.000 description 10
- -1 aldehyde ketone Chemical class 0.000 description 9
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 9
- 238000001914 filtration Methods 0.000 description 9
- 210000003205 muscle Anatomy 0.000 description 9
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 8
- 229910052731 fluorine Inorganic materials 0.000 description 8
- 239000011737 fluorine Substances 0.000 description 8
- 239000012085 test solution Substances 0.000 description 8
- 238000012360 testing method Methods 0.000 description 7
- 210000001519 tissue Anatomy 0.000 description 7
- 241000700159 Rattus Species 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 229960002390 flurbiprofen Drugs 0.000 description 6
- BHAAPTBBJKJZER-UHFFFAOYSA-N p-anisidine Chemical compound COC1=CC=C(N)C=C1 BHAAPTBBJKJZER-UHFFFAOYSA-N 0.000 description 6
- 230000001105 regulatory effect Effects 0.000 description 6
- 238000002835 absorbance Methods 0.000 description 5
- 150000002148 esters Chemical class 0.000 description 5
- SYTBZMRGLBWNTM-UHFFFAOYSA-N flurbiprofen Chemical compound FC1=CC(C(C(O)=O)C)=CC=C1C1=CC=CC=C1 SYTBZMRGLBWNTM-UHFFFAOYSA-N 0.000 description 5
- 230000008569 process Effects 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- 229960000935 dehydrated alcohol Drugs 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 210000004185 liver Anatomy 0.000 description 4
- 210000000056 organ Anatomy 0.000 description 4
- 230000003647 oxidation Effects 0.000 description 4
- 238000007254 oxidation reaction Methods 0.000 description 4
- 210000000952 spleen Anatomy 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 229960000583 acetic acid Drugs 0.000 description 3
- 238000010790 dilution Methods 0.000 description 3
- 239000012895 dilution Substances 0.000 description 3
- 230000000857 drug effect Effects 0.000 description 3
- 239000003480 eluent Substances 0.000 description 3
- 238000004945 emulsification Methods 0.000 description 3
- 210000002216 heart Anatomy 0.000 description 3
- 229960001680 ibuprofen Drugs 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 210000003734 kidney Anatomy 0.000 description 3
- 210000004072 lung Anatomy 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- 150000002978 peroxides Chemical class 0.000 description 3
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 206010028980 Neoplasm Diseases 0.000 description 2
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 2
- 229930003427 Vitamin E Natural products 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- YZXBAPSDXZZRGB-DOFZRALJSA-N arachidonic acid Chemical compound CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(O)=O YZXBAPSDXZZRGB-DOFZRALJSA-N 0.000 description 2
- 230000015556 catabolic process Effects 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 238000006731 degradation reaction Methods 0.000 description 2
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 2
- 239000012153 distilled water Substances 0.000 description 2
- 238000009513 drug distribution Methods 0.000 description 2
- 238000003255 drug test Methods 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 description 2
- 239000012362 glacial acetic acid Substances 0.000 description 2
- 239000004519 grease Substances 0.000 description 2
- 239000002960 lipid emulsion Substances 0.000 description 2
- 150000002632 lipids Chemical class 0.000 description 2
- 239000002075 main ingredient Substances 0.000 description 2
- 239000003002 pH adjusting agent Substances 0.000 description 2
- MHZZQFJGUZUBCN-UHFFFAOYSA-N propan-2-ol;2,2,4-trimethylpentane Chemical compound CC(C)O.CC(C)CC(C)(C)C MHZZQFJGUZUBCN-UHFFFAOYSA-N 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 2
- 235000019345 sodium thiosulphate Nutrition 0.000 description 2
- 238000004659 sterilization and disinfection Methods 0.000 description 2
- 238000004448 titration Methods 0.000 description 2
- 229940046009 vitamin E Drugs 0.000 description 2
- 235000019165 vitamin E Nutrition 0.000 description 2
- 239000011709 vitamin E Substances 0.000 description 2
- AYIRNRDRBQJXIF-NXEZZACHSA-N (-)-Florfenicol Chemical group CS(=O)(=O)C1=CC=C([C@@H](O)[C@@H](CF)NC(=O)C(Cl)Cl)C=C1 AYIRNRDRBQJXIF-NXEZZACHSA-N 0.000 description 1
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 1
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
- 102000013392 Carboxylesterase Human genes 0.000 description 1
- 108010051152 Carboxylesterase Proteins 0.000 description 1
- JZNWSCPGTDBMEW-UHFFFAOYSA-N Glycerophosphorylethanolamin Natural products NCCOP(O)(=O)OCC(O)CO JZNWSCPGTDBMEW-UHFFFAOYSA-N 0.000 description 1
- HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 239000005642 Oleic acid Substances 0.000 description 1
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 1
- 235000021314 Palmitic acid Nutrition 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 102000004005 Prostaglandin-endoperoxide synthases Human genes 0.000 description 1
- 108090000459 Prostaglandin-endoperoxide synthases Proteins 0.000 description 1
- 229920005654 Sephadex Polymers 0.000 description 1
- 239000012507 Sephadex™ Substances 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- ATBOMIWRCZXYSZ-XZBBILGWSA-N [1-[2,3-dihydroxypropoxy(hydroxy)phosphoryl]oxy-3-hexadecanoyloxypropan-2-yl] (9e,12e)-octadeca-9,12-dienoate Chemical compound CCCCCCCCCCCCCCCC(=O)OCC(COP(O)(=O)OCC(O)CO)OC(=O)CCCCCCC\C=C\C\C=C\CCCCC ATBOMIWRCZXYSZ-XZBBILGWSA-N 0.000 description 1
- AWUCVROLDVIAJX-UHFFFAOYSA-N alpha-glycerophosphate Natural products OCC(O)COP(O)(O)=O AWUCVROLDVIAJX-UHFFFAOYSA-N 0.000 description 1
- 230000036592 analgesia Effects 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 229940114079 arachidonic acid Drugs 0.000 description 1
- 235000021342 arachidonic acid Nutrition 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 238000005352 clarification Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- ZPWVASYFFYYZEW-UHFFFAOYSA-L dipotassium hydrogen phosphate Chemical compound [K+].[K+].OP([O-])([O-])=O ZPWVASYFFYYZEW-UHFFFAOYSA-L 0.000 description 1
- 238000002296 dynamic light scattering Methods 0.000 description 1
- 238000005265 energy consumption Methods 0.000 description 1
- 229940031098 ethanolamine Drugs 0.000 description 1
- LYCAIKOWRPUZTN-UHFFFAOYSA-N ethylene glycol Natural products OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 1
- 210000003191 femoral vein Anatomy 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 239000010419 fine particle Substances 0.000 description 1
- 238000011010 flushing procedure Methods 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 238000000265 homogenisation Methods 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 230000008676 import Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 235000013372 meat Nutrition 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 239000004005 microsphere Substances 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- HZAXFHJVJLSVMW-UHFFFAOYSA-N monoethanolamine hydrochloride Natural products NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 1
- 230000009854 mucosal lesion Effects 0.000 description 1
- WQEPLUUGTLDZJY-UHFFFAOYSA-N n-Pentadecanoic acid Natural products CCCCCCCCCCCCCCC(O)=O WQEPLUUGTLDZJY-UHFFFAOYSA-N 0.000 description 1
- IPCSVZSSVZVIGE-UHFFFAOYSA-N n-hexadecanoic acid Natural products CCCCCCCCCCCCCCCC(O)=O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 1
- VMPITZXILSNTON-UHFFFAOYSA-N o-anisidine Chemical compound COC1=CC=CC=C1N VMPITZXILSNTON-UHFFFAOYSA-N 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 230000036407 pain Effects 0.000 description 1
- 230000000149 penetrating effect Effects 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 150000008104 phosphatidylethanolamines Chemical class 0.000 description 1
- 238000005375 photometry Methods 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 230000002980 postoperative effect Effects 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 238000002203 pretreatment Methods 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- OLBCVFGFOZPWHH-UHFFFAOYSA-N propofol Chemical compound CC(C)C1=CC=CC(C(C)C)=C1O OLBCVFGFOZPWHH-UHFFFAOYSA-N 0.000 description 1
- 229960004134 propofol Drugs 0.000 description 1
- 150000003180 prostaglandins Chemical class 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000002390 rotary evaporation Methods 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 239000012047 saturated solution Substances 0.000 description 1
- 238000002798 spectrophotometry method Methods 0.000 description 1
- 238000013112 stability test Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 229960004274 stearic acid Drugs 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 238000003354 tissue distribution assay Methods 0.000 description 1
- 238000009827 uniform distribution Methods 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- 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
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/192—Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid
-
- 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
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
-
- 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
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
-
- 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
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/24—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids
-
- 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
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
-
- 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
- A61K9/10—Dispersions; Emulsions
- A61K9/107—Emulsions ; Emulsion preconcentrates; Micelles
-
- 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
- A61K9/10—Dispersions; Emulsions
- A61K9/107—Emulsions ; Emulsion preconcentrates; Micelles
- A61K9/1075—Microemulsions or submicron emulsions; Preconcentrates or solids thereof; Micelles, e.g. made of phospholipids or block copolymers
-
- 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]
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Molecular Biology (AREA)
- Biophysics (AREA)
- Dispersion Chemistry (AREA)
- Dermatology (AREA)
- Biochemistry (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Emergency Medicine (AREA)
- Medicinal Preparation (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
Description
Ke | 20min | 30min | 40min | 60min | |
实施例1 | 0.27 | 无明显漂油 | 无明显漂油 | 无明显漂油 | 轻微漂油 |
实施例2 | 0.28 | 无明显漂油 | 无明显漂油 | 无明显漂油 | 轻微漂油 |
实施例3 | 0.37 | 无明显漂油 | 无明显漂油 | 无明显漂油 | 轻微漂油 |
实施例4 | 0.18 | 无明显漂油 | 无明显漂油 | 无明显漂油 | 轻微漂油 |
实施例5 | 0.15 | 无明显漂油 | 无明显漂油 | 无明显漂油 | 轻微漂油 |
对比例1 | 0.63 | 无明显漂油 | 轻微漂油 | 轻微分层 | 明显分层、破乳 |
对比例2 | 0.72 | 无明显漂油 | 轻微漂油 | 轻微分层 | 明显分层、破乳 |
对比例3 | 0.65 | 无明显漂油 | 轻微漂油 | 轻微分层 | 明显分层、破乳 |
Claims (10)
Priority Applications (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201811175197.7A CN109223712B (zh) | 2018-10-10 | 2018-10-10 | 氟比洛芬酯注射用乳剂及其制备方法 |
PCT/CN2019/072562 WO2020073559A1 (zh) | 2018-10-10 | 2019-01-21 | 氟比洛芬酯注射用乳剂及其制备方法 |
US16/652,388 US11839590B2 (en) | 2018-10-10 | 2019-01-21 | Flurbiprofen axetil emulsion for injection and preparation method thereof |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201811175197.7A CN109223712B (zh) | 2018-10-10 | 2018-10-10 | 氟比洛芬酯注射用乳剂及其制备方法 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN109223712A true CN109223712A (zh) | 2019-01-18 |
CN109223712B CN109223712B (zh) | 2020-06-02 |
Family
ID=65055397
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201811175197.7A Active CN109223712B (zh) | 2018-10-10 | 2018-10-10 | 氟比洛芬酯注射用乳剂及其制备方法 |
Country Status (3)
Country | Link |
---|---|
US (1) | US11839590B2 (zh) |
CN (1) | CN109223712B (zh) |
WO (1) | WO2020073559A1 (zh) |
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2020073559A1 (zh) * | 2018-10-10 | 2020-04-16 | 武汉大安制药有限公司 | 氟比洛芬酯注射用乳剂及其制备方法 |
CN111296730A (zh) * | 2020-03-06 | 2020-06-19 | 广州市食品工业研究所有限公司 | 一种稳定性好的叶黄素纳米乳液及其制备方法 |
CN111671718A (zh) * | 2020-06-04 | 2020-09-18 | 山西普德药业有限公司 | 一种氟比洛芬酯注射液及其制备方法 |
CN112586742A (zh) * | 2020-12-15 | 2021-04-02 | 山东永春堂集团有限公司 | 一种元宝枫油乳剂的制备方法 |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1720031A (zh) * | 2002-12-06 | 2006-01-11 | 株式会社大塚制药工场 | 含丙泊酚的脂肪乳剂 |
CN102512367A (zh) * | 2011-12-26 | 2012-06-27 | 西安力邦制药有限公司 | 新型二十二碳六烯酸(dha)脂肪乳制剂配方和制备方法 |
CN102670502A (zh) * | 2012-05-17 | 2012-09-19 | 北京阜康仁生物制药科技有限公司 | S(+)-氟比洛芬酯注射乳剂 |
CN102988291A (zh) * | 2012-12-13 | 2013-03-27 | 哈药集团技术中心 | 一种氟比洛芬酯脂肪乳注射液组合物及其制备方法 |
Family Cites Families (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE3722540A1 (de) * | 1987-07-08 | 1989-01-19 | Fresenius Ag | Fettemulsion, verfahren zu ihrer herstellung und ihre verwendung |
CN104188905B (zh) | 2014-08-28 | 2016-08-24 | 河北一品制药有限公司 | 一种稳定的氟比洛芬酯微纳米乳液及其制备方法 |
CN104434901B (zh) | 2014-11-12 | 2016-03-02 | 桂林澳林制药有限责任公司 | 一种氟比洛芬酯的药物组合物 |
CN104922065B (zh) | 2015-06-11 | 2018-01-02 | 北京蓝丹医药科技有限公司 | 一种稳定的氟比洛芬酯药物组合物 |
WO2018146829A1 (ja) * | 2017-02-07 | 2018-08-16 | キユーピー株式会社 | 脂肪乳剤、及びその製造方法、脂肪乳剤の安定性を向上させる方法、並びに脂肪乳剤の安定性向上剤 |
CN109223712B (zh) * | 2018-10-10 | 2020-06-02 | 武汉大安制药有限公司 | 氟比洛芬酯注射用乳剂及其制备方法 |
-
2018
- 2018-10-10 CN CN201811175197.7A patent/CN109223712B/zh active Active
-
2019
- 2019-01-21 US US16/652,388 patent/US11839590B2/en active Active
- 2019-01-21 WO PCT/CN2019/072562 patent/WO2020073559A1/zh active Application Filing
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1720031A (zh) * | 2002-12-06 | 2006-01-11 | 株式会社大塚制药工场 | 含丙泊酚的脂肪乳剂 |
CN102512367A (zh) * | 2011-12-26 | 2012-06-27 | 西安力邦制药有限公司 | 新型二十二碳六烯酸(dha)脂肪乳制剂配方和制备方法 |
CN102670502A (zh) * | 2012-05-17 | 2012-09-19 | 北京阜康仁生物制药科技有限公司 | S(+)-氟比洛芬酯注射乳剂 |
CN102988291A (zh) * | 2012-12-13 | 2013-03-27 | 哈药集团技术中心 | 一种氟比洛芬酯脂肪乳注射液组合物及其制备方法 |
Non-Patent Citations (3)
Title |
---|
董广金: "10%静注脂肪乳的制备与性质考察", 《中国优秀硕士学位论文全文数据库医药卫生科技辑》 * |
郭建彬,等: "分步乳化法在制备乳化石蜡中的应用", 《科技风》 * |
陆军,等: "氟比洛芬酯脂微球注射液的制备及质量研究", 《天津药学》 * |
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2020073559A1 (zh) * | 2018-10-10 | 2020-04-16 | 武汉大安制药有限公司 | 氟比洛芬酯注射用乳剂及其制备方法 |
CN111296730A (zh) * | 2020-03-06 | 2020-06-19 | 广州市食品工业研究所有限公司 | 一种稳定性好的叶黄素纳米乳液及其制备方法 |
CN111671718A (zh) * | 2020-06-04 | 2020-09-18 | 山西普德药业有限公司 | 一种氟比洛芬酯注射液及其制备方法 |
CN112586742A (zh) * | 2020-12-15 | 2021-04-02 | 山东永春堂集团有限公司 | 一种元宝枫油乳剂的制备方法 |
Also Published As
Publication number | Publication date |
---|---|
WO2020073559A1 (zh) | 2020-04-16 |
US11839590B2 (en) | 2023-12-12 |
CN109223712B (zh) | 2020-06-02 |
US20210220303A1 (en) | 2021-07-22 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN109223712A (zh) | 氟比洛芬酯注射用乳剂及其制备方法 | |
Tarr et al. | Enhanced intestinal absorption of cyclosporine in rats through the reduction of emulsion droplet size | |
CN106420610B (zh) | 一种离子液体微乳及其应用 | |
CN103110579B (zh) | 前列地尔注射剂 | |
JP2012006931A (ja) | 疎水性治療剤の改善された送達のための組成物および方法 | |
CN109310643A (zh) | 含甘油脂肪酸酯衍生物或丙二醇脂肪酸酯衍生物的度他雄胺和他达拉非复合制剂及包含其的口服胶囊制剂 | |
CN102085185B (zh) | 无痛和低注射刺激的新型丙泊酚脂肪乳制剂配方和制备方法 | |
CN104644553B (zh) | 一种丹参酮ⅱa微乳制剂、丹参酮ⅱa微乳凝胶制剂以及它们的制备方法 | |
CN102526065B (zh) | 一种治疗心脑血管疾病的复方注射制剂及其制备方法 | |
CN105963254B (zh) | 一种辅酶q10药物组合物及其制备工艺 | |
CN101524459A (zh) | 一种大蒜素和大蒜油水包油型亚微乳剂及其制备方法 | |
CN108309954A (zh) | 一种茶多酚的卵磷脂基反六角相液晶药剂及制备方法 | |
CN104958257B (zh) | 一种隐丹参酮皮肤角质类脂体制剂及其制备方法 | |
CN104523591B (zh) | 无致敏性、无痛丙泊酚脂肪微乳冻干制剂配方和制备方法 | |
CN107095799B (zh) | 复合脂质体及其制备方法和应用 | |
CN109758423A (zh) | 使用维生素k1脂肪乳注射液治疗凝血功能障碍的方法 | |
CN100408033C (zh) | 银杏内酯b的脂肪乳剂及其制备方法 | |
CN1965805A (zh) | 辅酶q10亚微乳注射液及制备方法 | |
CN103330678A (zh) | 一种丹皮酚微海绵制剂及其制备方法 | |
CA3002387A1 (en) | Isotretinoin formulations and uses thereof | |
CN109806226A (zh) | 维生素k1脂肪乳注射液的用途 | |
CN109602706A (zh) | 一种阿魏酸纳米结构脂质载体及其制备方法 | |
CN112190574A (zh) | 神经酰胺磷脂复合物及其制备方法和应用 | |
CN105919974B (zh) | 鲑鱼降钙素磷脂复合物及其脂质纳米粒和制备方法 | |
CN105943606B (zh) | 一种用于治疗脑缺血的药物组合物及其制备方法 |
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 | ||
CP03 | Change of name, title or address | ||
CP03 | Change of name, title or address |
Address after: 430000 Jinyin Lake Ecological Park, Dongxihu District, Wuhan City, Hubei Province Patentee after: Yuanda Life Science (Wuhan) Co.,Ltd. Address before: 430040 Jinyin Lake Ecological Park, Dongxihu District, Wuhan City, Hubei Province Patentee before: WUHAN DOCAN PHARMACEUTICAL Co.,Ltd. |
|
PE01 | Entry into force of the registration of the contract for pledge of patent right |
Denomination of invention: Emulsion for flurbiprofen axetil injection and its preparation method Effective date of registration: 20220224 Granted publication date: 20200602 Pledgee: Wuhan area branch of Hubei pilot free trade zone of Bank of China Ltd. Pledgor: Yuanda Life Science (Wuhan) Co.,Ltd. Registration number: Y2022420000043 |
|
PE01 | Entry into force of the registration of the contract for pledge of patent right | ||
PC01 | Cancellation of the registration of the contract for pledge of patent right |
Date of cancellation: 20230403 Granted publication date: 20200602 Pledgee: Wuhan area branch of Hubei pilot free trade zone of Bank of China Ltd. Pledgor: Yuanda Life Science (Wuhan) Co.,Ltd. Registration number: Y2022420000043 |
|
PC01 | Cancellation of the registration of the contract for pledge of patent right | ||
CP03 | Change of name, title or address |
Address after: 430000 No.1 Xiaoxiang West Road, Dongxihu District, Wuhan City, Hubei Province Patentee after: Yuanda Medical Nutrition Science (Wuhan) Co.,Ltd. Country or region after: China Address before: 430000 Jinyin Lake Ecological Park, Dongxihu District, Wuhan City, Hubei Province Patentee before: Yuanda Life Science (Wuhan) Co.,Ltd. Country or region before: China |
|
CP03 | Change of name, title or address |