CA2536206C - Pharmaceutical products comprising bisphosphonates - Google Patents
Pharmaceutical products comprising bisphosphonates Download PDFInfo
- Publication number
- CA2536206C CA2536206C CA2536206A CA2536206A CA2536206C CA 2536206 C CA2536206 C CA 2536206C CA 2536206 A CA2536206 A CA 2536206A CA 2536206 A CA2536206 A CA 2536206A CA 2536206 C CA2536206 C CA 2536206C
- Authority
- CA
- Canada
- Prior art keywords
- container
- product according
- bisphosphonate
- solution
- acid
- 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.)
- Expired - Fee Related
Links
- 229940122361 Bisphosphonate Drugs 0.000 title claims abstract description 61
- 150000004663 bisphosphonates Chemical class 0.000 title claims abstract description 57
- 239000000825 pharmaceutical preparation Substances 0.000 title claims abstract description 16
- 229940127557 pharmaceutical product Drugs 0.000 title claims abstract description 13
- 229920003023 plastic Polymers 0.000 claims abstract description 52
- 239000004033 plastic Substances 0.000 claims abstract description 47
- 239000000463 material Substances 0.000 claims abstract description 24
- 239000000047 product Substances 0.000 claims description 67
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 60
- XRASPMIURGNCCH-UHFFFAOYSA-N zoledronic acid Chemical group OP(=O)(O)C(P(O)(O)=O)(O)CN1C=CN=C1 XRASPMIURGNCCH-UHFFFAOYSA-N 0.000 claims description 54
- 238000004659 sterilization and disinfection Methods 0.000 claims description 43
- 229960004276 zoledronic acid Drugs 0.000 claims description 40
- 239000000203 mixture Substances 0.000 claims description 38
- -1 polypropylene Polymers 0.000 claims description 31
- 230000001954 sterilising effect Effects 0.000 claims description 28
- 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 23
- 229930195725 Mannitol Natural products 0.000 claims description 23
- 239000000594 mannitol Substances 0.000 claims description 23
- 235000010355 mannitol Nutrition 0.000 claims description 23
- 238000000034 method Methods 0.000 claims description 21
- 239000003795 chemical substances by application Substances 0.000 claims description 20
- 230000008569 process Effects 0.000 claims description 19
- 239000001509 sodium citrate Substances 0.000 claims description 19
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical group O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 claims description 17
- 238000001802 infusion Methods 0.000 claims description 16
- 150000003839 salts Chemical class 0.000 claims description 16
- 238000005406 washing Methods 0.000 claims description 16
- 239000002158 endotoxin Substances 0.000 claims description 15
- 238000004519 manufacturing process Methods 0.000 claims description 14
- 239000007857 degradation product Substances 0.000 claims description 13
- WRUUGTRCQOWXEG-UHFFFAOYSA-N pamidronate Chemical compound NCCC(O)(P(O)(O)=O)P(O)(O)=O WRUUGTRCQOWXEG-UHFFFAOYSA-N 0.000 claims description 13
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 12
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims description 12
- 238000011049 filling Methods 0.000 claims description 12
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical group C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 10
- 239000004743 Polypropylene Substances 0.000 claims description 10
- 229960003978 pamidronic acid Drugs 0.000 claims description 10
- 229920001155 polypropylene Polymers 0.000 claims description 10
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 claims description 9
- 239000006227 byproduct Substances 0.000 claims description 9
- 229910052708 sodium Inorganic materials 0.000 claims description 9
- 239000011734 sodium Substances 0.000 claims description 9
- 230000036512 infertility Effects 0.000 claims description 7
- 229920000642 polymer Polymers 0.000 claims description 7
- 238000001212 derivatisation Methods 0.000 claims description 6
- 150000007530 organic bases Chemical class 0.000 claims description 6
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 claims description 5
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 claims description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 5
- 238000010668 complexation reaction Methods 0.000 claims description 5
- 229960004063 propylene glycol Drugs 0.000 claims description 5
- 239000011347 resin Substances 0.000 claims description 5
- 229920005989 resin Polymers 0.000 claims description 5
- 239000000600 sorbitol Substances 0.000 claims description 5
- 239000004698 Polyethylene Substances 0.000 claims description 4
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical group [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 claims description 4
- 239000011888 foil Substances 0.000 claims description 4
- 229920000573 polyethylene Polymers 0.000 claims description 4
- 238000004366 reverse phase liquid chromatography Methods 0.000 claims description 4
- 239000001488 sodium phosphate Substances 0.000 claims description 4
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 claims description 4
- 229910000162 sodium phosphate Inorganic materials 0.000 claims description 3
- 235000000346 sugar Nutrition 0.000 claims description 3
- 150000002148 esters Chemical class 0.000 claims description 2
- 238000004128 high performance liquid chromatography Methods 0.000 claims description 2
- 238000004255 ion exchange chromatography Methods 0.000 claims description 2
- 229910000160 potassium phosphate Inorganic materials 0.000 claims description 2
- 235000011009 potassium phosphates Nutrition 0.000 claims description 2
- 239000001632 sodium acetate Substances 0.000 claims description 2
- 235000017281 sodium acetate Nutrition 0.000 claims description 2
- 239000006172 buffering agent Substances 0.000 claims 4
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims 3
- 239000012611 container material Substances 0.000 claims 3
- WKBPZYKAUNRMKP-UHFFFAOYSA-N 1-[2-(2,4-dichlorophenyl)pentyl]1,2,4-triazole Chemical compound C=1C=C(Cl)C=C(Cl)C=1C(CCC)CN1C=NC=N1 WKBPZYKAUNRMKP-UHFFFAOYSA-N 0.000 claims 1
- 229920002633 Kraton (polymer) Polymers 0.000 claims 1
- 238000005251 capillar electrophoresis Methods 0.000 claims 1
- HLWRUJAIJJEZDL-UHFFFAOYSA-M sodium;2-[2-[bis(carboxymethyl)amino]ethyl-(carboxymethyl)amino]acetate Chemical compound [Na+].OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC([O-])=O HLWRUJAIJJEZDL-UHFFFAOYSA-M 0.000 claims 1
- 239000000243 solution Substances 0.000 abstract description 80
- 239000003978 infusion fluid Substances 0.000 abstract description 3
- 239000008215 water for injection Substances 0.000 description 46
- 239000002253 acid Substances 0.000 description 28
- 235000002639 sodium chloride Nutrition 0.000 description 23
- 238000009472 formulation Methods 0.000 description 22
- 239000008364 bulk solution Substances 0.000 description 19
- 238000003756 stirring Methods 0.000 description 19
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
- 239000011521 glass Substances 0.000 description 16
- 239000004411 aluminium Substances 0.000 description 13
- 229910052782 aluminium Inorganic materials 0.000 description 13
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 13
- 239000004615 ingredient Substances 0.000 description 13
- 239000008186 active pharmaceutical agent Substances 0.000 description 12
- 229940088679 drug related substance Drugs 0.000 description 12
- 238000002360 preparation method Methods 0.000 description 12
- 239000002585 base Substances 0.000 description 11
- 238000013329 compounding Methods 0.000 description 11
- 239000011148 porous material Substances 0.000 description 11
- 230000009467 reduction Effects 0.000 description 10
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 9
- 229910001220 stainless steel Inorganic materials 0.000 description 8
- 239000010935 stainless steel Substances 0.000 description 8
- 229960005391 zoledronic acid anhydrous Drugs 0.000 description 8
- FUXFIVRTGHOMSO-UHFFFAOYSA-N (1-hydroxy-2-imidazol-1-yl-1-phosphonoethyl)phosphonic acid;hydrate Chemical compound O.OP(=O)(O)C(P(O)(O)=O)(O)CN1C=CN=C1 FUXFIVRTGHOMSO-UHFFFAOYSA-N 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 7
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 7
- 239000000546 pharmaceutical excipient Substances 0.000 description 7
- 238000012360 testing method Methods 0.000 description 7
- 229950011303 zoledronic acid monohydrate Drugs 0.000 description 7
- 238000003556 assay Methods 0.000 description 6
- 230000015556 catabolic process Effects 0.000 description 6
- 238000006731 degradation reaction Methods 0.000 description 6
- 239000002552 dosage form Substances 0.000 description 6
- 238000002347 injection Methods 0.000 description 6
- 239000007924 injection Substances 0.000 description 6
- 239000002245 particle Substances 0.000 description 6
- 235000011121 sodium hydroxide Nutrition 0.000 description 6
- 238000003860 storage Methods 0.000 description 6
- 238000001514 detection method Methods 0.000 description 5
- 238000011020 pilot scale process Methods 0.000 description 5
- 239000002244 precipitate Substances 0.000 description 5
- FGBXDQWECLPOGZ-UHFFFAOYSA-N [Na].O.O.O.O.O.[Na] Chemical compound [Na].O.O.O.O.O.[Na] FGBXDQWECLPOGZ-UHFFFAOYSA-N 0.000 description 4
- 125000000217 alkyl group Chemical group 0.000 description 4
- 150000001768 cations Chemical class 0.000 description 4
- 230000008859 change Effects 0.000 description 4
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 4
- 238000012545 processing Methods 0.000 description 4
- 239000011780 sodium chloride Substances 0.000 description 4
- 235000010356 sorbitol Nutrition 0.000 description 4
- HRXKRNGNAMMEHJ-UHFFFAOYSA-K trisodium citrate Chemical compound [Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O HRXKRNGNAMMEHJ-UHFFFAOYSA-K 0.000 description 4
- PMXAPNNYCFBALB-UHFFFAOYSA-N (1-hydroxy-1-phosphono-3-pyrrolidin-1-ylpropyl)phosphonic acid Chemical compound OP(=O)(O)C(P(O)(O)=O)(O)CCN1CCCC1 PMXAPNNYCFBALB-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 208000006386 Bone Resorption Diseases 0.000 description 3
- QXNVGIXVLWOKEQ-UHFFFAOYSA-N Disodium Chemical class [Na][Na] QXNVGIXVLWOKEQ-UHFFFAOYSA-N 0.000 description 3
- 208000037147 Hypercalcaemia Diseases 0.000 description 3
- MPBVHIBUJCELCL-UHFFFAOYSA-N Ibandronate Chemical compound CCCCCN(C)CCC(O)(P(O)(O)=O)P(O)(O)=O MPBVHIBUJCELCL-UHFFFAOYSA-N 0.000 description 3
- 206010028980 Neoplasm Diseases 0.000 description 3
- 208000010191 Osteitis Deformans Diseases 0.000 description 3
- 208000001132 Osteoporosis Diseases 0.000 description 3
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 3
- IIDJRNMFWXDHID-UHFFFAOYSA-N Risedronic acid Chemical compound OP(=O)(O)C(P(O)(O)=O)(O)CC1=CC=CN=C1 IIDJRNMFWXDHID-UHFFFAOYSA-N 0.000 description 3
- DKJJVAGXPKPDRL-UHFFFAOYSA-N Tiludronic acid Chemical compound OP(O)(=O)C(P(O)(O)=O)SC1=CC=C(Cl)C=C1 DKJJVAGXPKPDRL-UHFFFAOYSA-N 0.000 description 3
- 230000002378 acidificating effect Effects 0.000 description 3
- 125000003277 amino group Chemical group 0.000 description 3
- 230000024279 bone resorption Effects 0.000 description 3
- 239000011575 calcium Substances 0.000 description 3
- 235000015165 citric acid Nutrition 0.000 description 3
- 229920001577 copolymer Polymers 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 229940126534 drug product Drugs 0.000 description 3
- 238000011156 evaluation Methods 0.000 description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 3
- 230000000148 hypercalcaemia Effects 0.000 description 3
- 239000012535 impurity Substances 0.000 description 3
- 238000011065 in-situ storage Methods 0.000 description 3
- 150000002500 ions Chemical class 0.000 description 3
- 238000002386 leaching Methods 0.000 description 3
- 239000011777 magnesium Substances 0.000 description 3
- 229910052700 potassium Inorganic materials 0.000 description 3
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- 238000011084 recovery Methods 0.000 description 3
- 229920006395 saturated elastomer Polymers 0.000 description 3
- 159000000000 sodium salts Chemical class 0.000 description 3
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- 230000004580 weight loss Effects 0.000 description 3
- OGSPWJRAVKPPFI-UHFFFAOYSA-N Alendronic Acid Chemical compound NCCCC(O)(P(O)(O)=O)P(O)(O)=O OGSPWJRAVKPPFI-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
- DBVJJBKOTRCVKF-UHFFFAOYSA-N Etidronic acid Chemical compound OP(=O)(O)C(O)(C)P(O)(O)=O DBVJJBKOTRCVKF-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
- 208000027868 Paget disease Diseases 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
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- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 2
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- 239000004809 Teflon Substances 0.000 description 2
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- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
- NPLHDPAQRZJWHX-UHFFFAOYSA-N [5,5-bis(diethoxyphosphoryl)-1,4-dihydropyrazol-3-yl]-phenylmethanone Chemical compound N1C(P(=O)(OCC)OCC)(P(=O)(OCC)OCC)CC(C(=O)C=2C=CC=CC=2)=N1 NPLHDPAQRZJWHX-UHFFFAOYSA-N 0.000 description 2
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- 239000012632 extractable Substances 0.000 description 2
- RULHPTADXJPDSN-UHFFFAOYSA-M hydron;tetrahexylazanium;sulfate Chemical compound OS([O-])(=O)=O.CCCCCC[N+](CCCCCC)(CCCCCC)CCCCCC RULHPTADXJPDSN-UHFFFAOYSA-M 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 2
- 208000030915 hypercalcemia disease Diseases 0.000 description 2
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- 159000000001 potassium salts Chemical class 0.000 description 2
- VWDWKYIASSYTQR-UHFFFAOYSA-N sodium nitrate Chemical compound [Na+].[O-][N+]([O-])=O VWDWKYIASSYTQR-UHFFFAOYSA-N 0.000 description 2
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- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 2
- SOBHUZYZLFQYFK-UHFFFAOYSA-K trisodium;hydroxy-[[phosphonatomethyl(phosphonomethyl)amino]methyl]phosphinate Chemical compound [Na+].[Na+].[Na+].OP(O)(=O)CN(CP(O)([O-])=O)CP([O-])([O-])=O SOBHUZYZLFQYFK-UHFFFAOYSA-K 0.000 description 2
- 239000011701 zinc Substances 0.000 description 2
- HDTRYLNUVZCQOY-UHFFFAOYSA-N α-D-glucopyranosyl-α-D-glucopyranoside Natural products OC1C(O)C(O)C(CO)OC1OC1C(O)C(O)C(O)C(CO)O1 HDTRYLNUVZCQOY-UHFFFAOYSA-N 0.000 description 1
- RDFHOSXBGDLRQF-UHFFFAOYSA-N (2-anilino-1-phosphono-2-sulfanylideneethyl)phosphonic acid Chemical compound OP(O)(=O)C(P(O)(O)=O)C(=S)NC1=CC=CC=C1 RDFHOSXBGDLRQF-UHFFFAOYSA-N 0.000 description 1
- FBSQLNMIJFINOJ-UHFFFAOYSA-N (2-imidazol-1-yl-1-phosphonoethyl)phosphonic acid Chemical compound OP(O)(=O)C(P(O)(O)=O)CN1C=CN=C1 FBSQLNMIJFINOJ-UHFFFAOYSA-N 0.000 description 1
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- QFMZQPDHXULLKC-UHFFFAOYSA-N 1,2-bis(diphenylphosphino)ethane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)CCP(C=1C=CC=CC=1)C1=CC=CC=C1 QFMZQPDHXULLKC-UHFFFAOYSA-N 0.000 description 1
- LCOBNBPKWCKAKF-UHFFFAOYSA-N 1-[3,6-dihydroxy-2,4-bis(phenylmethoxy)phenyl]ethanone Chemical compound OC1=C(OCC=2C=CC=CC=2)C(C(=O)C)=C(O)C=C1OCC1=CC=CC=C1 LCOBNBPKWCKAKF-UHFFFAOYSA-N 0.000 description 1
- HLNJFEXZDGURGZ-UHFFFAOYSA-M 1-methylpyridin-1-ium;iodide Chemical class [I-].C[N+]1=CC=CC=C1 HLNJFEXZDGURGZ-UHFFFAOYSA-M 0.000 description 1
- OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 description 1
- QWENRTYMTSOGBR-UHFFFAOYSA-N 1H-1,2,3-Triazole Chemical compound C=1C=NNN=1 QWENRTYMTSOGBR-UHFFFAOYSA-N 0.000 description 1
- SLRMQYXOBQWXCR-UHFFFAOYSA-N 2154-56-5 Chemical group [CH2]C1=CC=CC=C1 SLRMQYXOBQWXCR-UHFFFAOYSA-N 0.000 description 1
- NSPMIYGKQJPBQR-UHFFFAOYSA-N 4H-1,2,4-triazole Chemical compound C=1N=CNN=1 NSPMIYGKQJPBQR-UHFFFAOYSA-N 0.000 description 1
- YLKRUSPZOTYMAT-YFKPBYRVSA-N 6-hydroxy-L-dopa Chemical compound OC(=O)[C@@H](N)CC1=CC(O)=C(O)C=C1O YLKRUSPZOTYMAT-YFKPBYRVSA-N 0.000 description 1
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- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
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- A61K31/00—Medicinal preparations containing organic active ingredients
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/66—Phosphorus compounds
- A61K31/662—Phosphorus acids or esters thereof having P—C bonds, e.g. foscarnet, trichlorfon
- A61K31/663—Compounds having two or more phosphorus acid groups or esters thereof, e.g. clodronic acid, pamidronic acid
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- A—HUMAN NECESSITIES
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- 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
- A61K47/12—Carboxylic acids; Salts or anhydrides thereof
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- 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
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Physical Education & Sports Medicine (AREA)
- Organic Chemistry (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Rheumatology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Dermatology (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Oncology (AREA)
- Inorganic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Medical Preparation Storing Or Oral Administration Devices (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US50440203P | 2003-09-18 | 2003-09-18 | |
| US60/504,402 | 2003-09-18 | ||
| PCT/EP2004/010470 WO2005025551A2 (en) | 2003-09-18 | 2004-09-17 | Pharmaceutical products comprising bisphosphonates |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2536206A1 CA2536206A1 (en) | 2005-03-24 |
| CA2536206C true CA2536206C (en) | 2010-08-24 |
Family
ID=34312464
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2536206A Expired - Fee Related CA2536206C (en) | 2003-09-18 | 2004-09-17 | Pharmaceutical products comprising bisphosphonates |
Country Status (23)
| Country | Link |
|---|---|
| US (1) | US7932241B2 (OSRAM) |
| EP (1) | EP1663314A2 (OSRAM) |
| JP (1) | JP4802096B2 (OSRAM) |
| KR (1) | KR101015718B1 (OSRAM) |
| CN (1) | CN1852739A (OSRAM) |
| AR (1) | AR045670A1 (OSRAM) |
| AU (1) | AU2004271731B2 (OSRAM) |
| BR (1) | BRPI0414562A (OSRAM) |
| CA (1) | CA2536206C (OSRAM) |
| CO (1) | CO5680461A2 (OSRAM) |
| EC (1) | ECSP066419A (OSRAM) |
| IL (1) | IL173766A (OSRAM) |
| IS (1) | IS8351A (OSRAM) |
| MA (1) | MA28078A1 (OSRAM) |
| MY (1) | MY141763A (OSRAM) |
| NO (1) | NO20061682L (OSRAM) |
| NZ (1) | NZ545343A (OSRAM) |
| PE (1) | PE20050468A1 (OSRAM) |
| RU (1) | RU2358739C2 (OSRAM) |
| TN (1) | TNSN06084A1 (OSRAM) |
| TW (1) | TWI345977B (OSRAM) |
| WO (1) | WO2005025551A2 (OSRAM) |
| ZA (1) | ZA200601209B (OSRAM) |
Families Citing this family (25)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| MY141763A (en) | 2003-09-18 | 2010-06-30 | Novartis Ag | Pharmaceutical products comprising bisphosphonates |
| US20050119230A1 (en) * | 2003-09-18 | 2005-06-02 | Alexandra Glausch | Pharmaceutical products comprising bisphosphonated |
| WO2008059059A1 (en) * | 2006-11-17 | 2008-05-22 | Besins Healthcare | Pharmaceutical compositions comprising a bisphosphonate compound |
| EP1923049A1 (en) * | 2006-11-17 | 2008-05-21 | Besins Healthcare | Pharmaceutical compositions comprising a bisphosphonate compound |
| FI3345607T3 (fi) * | 2006-12-29 | 2022-11-30 | Menetelmiä luun kasvun muuttamiseksi antamalla SOST- tai WISE-antagonistia tai antagonistia | |
| JP5607408B2 (ja) * | 2009-04-03 | 2014-10-15 | 帝人ファーマ株式会社 | アレンドロン酸含有注射剤 |
| US20160016982A1 (en) | 2009-07-31 | 2016-01-21 | Thar Pharmaceuticals, Inc. | Crystallization method and bioavailability |
| US9169279B2 (en) | 2009-07-31 | 2015-10-27 | Thar Pharmaceuticals, Inc. | Crystallization method and bioavailability |
| KR101813728B1 (ko) | 2009-07-31 | 2017-12-29 | 그뤼넨탈 게엠베하 | 결정화 방법 및 생체이용률 |
| US8882740B2 (en) * | 2009-12-23 | 2014-11-11 | Stryker Trauma Gmbh | Method of delivering a biphosphonate and/or strontium ranelate below the surface of a bone |
| EP2363111A1 (en) | 2010-03-01 | 2011-09-07 | Combino Pharm, S.L. | Stable pharmaceutical composition comprising bisphosphonate |
| WO2011132826A1 (en) * | 2010-04-19 | 2011-10-27 | Snu R&Db Foundation | Transdermal drug delivery system and pharmaceutical composition for preventing or treating bone diseases |
| WO2012071517A2 (en) | 2010-11-24 | 2012-05-31 | Thar Pharmaceuticals, Inc. | Novel crystalline forms |
| EP2712611A1 (en) * | 2012-09-27 | 2014-04-02 | B. Braun Melsungen AG | Stabilized aqueous compositions of neuromuscular blocking agents |
| RU2506085C1 (ru) * | 2013-01-30 | 2014-02-10 | Федеральное бюджетное учреждение науки "Государственный научный центр вирусологии и биотехнологии "Вектор" (ФБУН ГНЦ ВБ "Вектор") | Тетраэтил-2-(2,2,6,6-тетраметилпиперидин-4-иламино)-этилен-1,1-бисфосфонат, обладающий противоопухолевой активностью |
| CN104721132B (zh) * | 2013-12-21 | 2018-05-18 | 石药集团恩必普药业有限公司 | 一种唑来膦酸注射液及其制备方法 |
| US10098813B2 (en) * | 2014-09-03 | 2018-10-16 | Sun Pharmaceutical Industries Limited | Perfusion dosage form |
| GB201505347D0 (en) * | 2015-03-27 | 2015-05-13 | Salupont Consulting Ltd | Sterilisation of s-nitrosothiols |
| CN108261393B (zh) * | 2015-09-27 | 2020-10-27 | 山东则正医药技术有限公司 | 一种含有唑来膦酸的注射用药物组合物 |
| WO2017138023A1 (en) | 2016-02-09 | 2017-08-17 | Sun Pharmaceutical Industries Ltd. | Perfusion system |
| US10195218B2 (en) | 2016-05-31 | 2019-02-05 | Grunenthal Gmbh | Crystallization method and bioavailability |
| CN111655291A (zh) * | 2017-08-28 | 2020-09-11 | 阿斯德拉有限责任公司 | 环糊精在涉及磷脂失调的疾病和病症中的用途 |
| JP2020535235A (ja) * | 2017-09-28 | 2020-12-03 | アスデラ エルエルシー | リン脂質の調節異常が関与する疾患および障害におけるシクロデキストリンの使用 |
| CN110161168B (zh) * | 2018-02-12 | 2022-12-20 | 四川科伦药物研究院有限公司 | 唑来膦酸及其杂质的高效液相色谱检测方法 |
| JP7704740B2 (ja) | 2019-09-16 | 2025-07-08 | アムジエン・インコーポレーテツド | 薬物送達デバイスの外部滅菌の方法 |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0275821B1 (de) * | 1986-11-21 | 1992-02-26 | Ciba-Geigy Ag | Neue substituierte Alkandiphosphonsäuren |
| JP3672342B2 (ja) * | 1994-09-26 | 2005-07-20 | アステラス製薬株式会社 | ビスホスホン酸又はその誘導体を含有する注射液とその安定化方法、及び注射液アンプル |
| FR2740686B1 (fr) * | 1995-11-03 | 1998-01-16 | Sanofi Sa | Formulation pharmaceutique lyophilisee stable |
| GB0012209D0 (en) * | 2000-05-19 | 2000-07-12 | Novartis Ag | Organic compounds |
| AU2001293473A1 (en) | 2000-09-18 | 2002-03-26 | Mayne Pharma International Pty Ltd | Diphosphonate solutions |
| US6709674B2 (en) | 2001-05-02 | 2004-03-23 | Gensia Sicor Pharmaceuticals, Inc. | Injectable pamidronate disodium |
| CA2372450A1 (en) * | 2001-05-10 | 2001-09-19 | Pharmaceutical Partners Of Canada Inc. | Liquid injectable formulation of disodium pamidronate |
| MY141763A (en) | 2003-09-18 | 2010-06-30 | Novartis Ag | Pharmaceutical products comprising bisphosphonates |
-
2004
- 2004-09-15 MY MYPI20043727A patent/MY141763A/en unknown
- 2004-09-16 PE PE2004000900A patent/PE20050468A1/es not_active Application Discontinuation
- 2004-09-16 AR ARP040103333A patent/AR045670A1/es unknown
- 2004-09-17 TW TW093128260A patent/TWI345977B/zh not_active IP Right Cessation
- 2004-09-17 US US10/570,339 patent/US7932241B2/en not_active Expired - Fee Related
- 2004-09-17 EP EP04765362A patent/EP1663314A2/en not_active Ceased
- 2004-09-17 CA CA2536206A patent/CA2536206C/en not_active Expired - Fee Related
- 2004-09-17 WO PCT/EP2004/010470 patent/WO2005025551A2/en not_active Ceased
- 2004-09-17 AU AU2004271731A patent/AU2004271731B2/en not_active Ceased
- 2004-09-17 BR BRPI0414562-3A patent/BRPI0414562A/pt not_active Application Discontinuation
- 2004-09-17 JP JP2006526598A patent/JP4802096B2/ja not_active Expired - Lifetime
- 2004-09-17 NZ NZ545343A patent/NZ545343A/en not_active IP Right Cessation
- 2004-09-17 RU RU2006112596/15A patent/RU2358739C2/ru not_active IP Right Cessation
- 2004-09-17 CN CNA2004800269883A patent/CN1852739A/zh active Pending
- 2004-09-17 KR KR1020067005455A patent/KR101015718B1/ko not_active Expired - Fee Related
-
2006
- 2006-02-10 ZA ZA200601209A patent/ZA200601209B/en unknown
- 2006-02-16 IL IL173766A patent/IL173766A/en not_active IP Right Cessation
- 2006-03-13 IS IS8351A patent/IS8351A/is unknown
- 2006-03-13 EC EC2006006419A patent/ECSP066419A/es unknown
- 2006-03-17 TN TNP2006000084A patent/TNSN06084A1/en unknown
- 2006-03-21 CO CO06027690A patent/CO5680461A2/es unknown
- 2006-03-27 MA MA28895A patent/MA28078A1/fr unknown
- 2006-04-12 NO NO20061682A patent/NO20061682L/no not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| AU2004271731B2 (en) | 2008-07-24 |
| RU2006112596A (ru) | 2007-11-10 |
| IL173766A0 (en) | 2006-07-05 |
| US20070015736A1 (en) | 2007-01-18 |
| JP2007505861A (ja) | 2007-03-15 |
| MA28078A1 (fr) | 2006-08-01 |
| NZ545343A (en) | 2010-08-27 |
| KR20060087568A (ko) | 2006-08-02 |
| JP4802096B2 (ja) | 2011-10-26 |
| AU2004271731A1 (en) | 2005-03-24 |
| MY141763A (en) | 2010-06-30 |
| PE20050468A1 (es) | 2005-10-03 |
| CN1852739A (zh) | 2006-10-25 |
| TW200522969A (en) | 2005-07-16 |
| IS8351A (is) | 2006-03-13 |
| KR101015718B1 (ko) | 2011-02-22 |
| AR045670A1 (es) | 2005-11-02 |
| TNSN06084A1 (en) | 2007-10-03 |
| NO20061682L (no) | 2006-06-14 |
| ZA200601209B (en) | 2007-04-25 |
| IL173766A (en) | 2012-10-31 |
| EP1663314A2 (en) | 2006-06-07 |
| CA2536206A1 (en) | 2005-03-24 |
| ECSP066419A (es) | 2006-09-18 |
| BRPI0414562A (pt) | 2006-11-07 |
| WO2005025551A3 (en) | 2006-01-12 |
| TWI345977B (en) | 2011-08-01 |
| RU2358739C2 (ru) | 2009-06-20 |
| WO2005025551A2 (en) | 2005-03-24 |
| CO5680461A2 (es) | 2006-09-29 |
| US7932241B2 (en) | 2011-04-26 |
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Legal Events
| Date | Code | Title | Description |
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| EEER | Examination request | ||
| MKLA | Lapsed |
Effective date: 20170918 |