JP2009528276A5 - - Google Patents

Info

Publication number

JP2009528276A5

JP2009528276A5 JP2008554395A JP2008554395A JP2009528276A5 JP 2009528276 A5 JP2009528276 A5 JP 2009528276A5 JP 2008554395 A JP2008554395 A JP 2008554395A JP 2008554395 A JP2008554395 A JP 2008554395A JP 2009528276 A5 JP2009528276 A5 JP 2009528276A5

Authority

JP

Japan

Prior art keywords

rapamycin

liquid formulation

pharmaceutically acceptable

formulation

liquid

Prior art date

2007-02-09

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

• Espacenet
• Global Dossier
• Discuss

• 239000012669 liquid formulation Substances 0.000 claims 42
• 229960002930 sirolimus Drugs 0.000 claims 39
• QFJCIRLUMZQUOT-HPLJOQBZSA-N sirolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 QFJCIRLUMZQUOT-HPLJOQBZSA-N 0.000 claims 31
• ZAHRKKWIAAJSAO-UHFFFAOYSA-N rapamycin Natural products COCC(O)C(=C/C(C)C(=O)CC(OC(=O)C1CCCCN1C(=O)C(=O)C2(O)OC(CC(OC)C(=CC=CC=CC(C)CC(C)C(=O)C)C)CCC2C)C(C)CC3CCC(O)C(C3)OC)C ZAHRKKWIAAJSAO-UHFFFAOYSA-N 0.000 claims 27
• 239000013543 active substance Substances 0.000 claims 14
• 238000000034 method Methods 0.000 claims 14
• 238000009472 formulation Methods 0.000 claims 13
• 239000000203 mixture Substances 0.000 claims 13
• 150000003839 salts Chemical class 0.000 claims 10
• -1 AP23841 Chemical compound 0.000 claims 9
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims 9
• 239000003814 drug Substances 0.000 claims 9
• 239000001301 oxygen Substances 0.000 claims 9
• 229910052760 oxygen Inorganic materials 0.000 claims 9
• 229940124597 therapeutic agent Drugs 0.000 claims 9
• 150000002148 esters Chemical class 0.000 claims 8
• 239000007788 liquid Substances 0.000 claims 8
• 238000002360 preparation method Methods 0.000 claims 7
• 239000007789 gas Substances 0.000 claims 6
• 239000000651 prodrug Substances 0.000 claims 6
• 229940002612 prodrug Drugs 0.000 claims 6
• HKVAMNSJSFKALM-GKUWKFKPSA-N Everolimus Chemical compound C1C[C@@H](OCCO)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 HKVAMNSJSFKALM-GKUWKFKPSA-N 0.000 claims 5
• QJJXYPPXXYFBGM-LFZNUXCKSA-N Tacrolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1\C=C(/C)[C@@H]1[C@H](C)[C@@H](O)CC(=O)[C@H](CC=C)/C=C(C)/C[C@H](C)C[C@H](OC)[C@H]([C@H](C[C@H]2C)OC)O[C@@]2(O)C(=O)C(=O)N2CCCC[C@H]2C(=O)O1 QJJXYPPXXYFBGM-LFZNUXCKSA-N 0.000 claims 5
• CBPNZQVSJQDFBE-FUXHJELOSA-N Temsirolimus Chemical compound C1C[C@@H](OC(=O)C(C)(CO)CO)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 CBPNZQVSJQDFBE-FUXHJELOSA-N 0.000 claims 5
• 229960005167 everolimus Drugs 0.000 claims 5
• KASDHRXLYQOAKZ-ZPSXYTITSA-N pimecrolimus Chemical compound C/C([C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@]2(O)O[C@@H]([C@H](C[C@H]2C)OC)[C@@H](OC)C[C@@H](C)C/C(C)=C/[C@H](C(C[C@H](O)[C@H]1C)=O)CC)=C\[C@@H]1CC[C@@H](Cl)[C@H](OC)C1 KASDHRXLYQOAKZ-ZPSXYTITSA-N 0.000 claims 5
• 229960005330 pimecrolimus Drugs 0.000 claims 5
• 229960001967 tacrolimus Drugs 0.000 claims 5
• QJJXYPPXXYFBGM-SHYZHZOCSA-N tacrolimus Natural products CO[C@H]1C[C@H](CC[C@@H]1O)C=C(C)[C@H]2OC(=O)[C@H]3CCCCN3C(=O)C(=O)[C@@]4(O)O[C@@H]([C@H](C[C@H]4C)OC)[C@@H](C[C@H](C)CC(=C[C@@H](CC=C)C(=O)C[C@H](O)[C@H]2C)C)OC QJJXYPPXXYFBGM-SHYZHZOCSA-N 0.000 claims 5
• 229960000235 temsirolimus Drugs 0.000 claims 5
• CGTADGCBEXYWNE-JUKNQOCSSA-N zotarolimus Chemical compound N1([C@H]2CC[C@@H](C[C@@H](C)[C@H]3OC(=O)[C@@H]4CCCCN4C(=O)C(=O)[C@@]4(O)[C@H](C)CC[C@H](O4)C[C@@H](/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C3)OC)C[C@H]2OC)C=NN=N1 CGTADGCBEXYWNE-JUKNQOCSSA-N 0.000 claims 5
• 229950009819 zotarolimus Drugs 0.000 claims 5
• 102000018679 Tacrolimus Binding Proteins Human genes 0.000 claims 4
• 108010027179 Tacrolimus Binding Proteins Proteins 0.000 claims 4
• 239000011261 inert gas Substances 0.000 claims 4
• OUNADCPYEMRCEK-AHTHDSRYSA-N (1R,9S,12S,15R,16E,18R,19R,21R,23S,24Z,26E,28E,32S,35R)-1,18-dihydroxy-12-[(2R)-1-[(1S,3R,4R)-4-hydroxy-3-methoxycyclohexyl]propan-2-yl]-19-methoxy-15,17,21,23,29,35-hexamethyl-11,36-dioxa-4-azatricyclo[30.3.1.04,9]hexatriaconta-16,24,26,28-tetraene-2,3,10,14,20-pentone Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2CC\C(C)=C\C=C\C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 OUNADCPYEMRCEK-AHTHDSRYSA-N 0.000 claims 3
• 102000000521 Immunophilins Human genes 0.000 claims 3
• 108010016648 Immunophilins Proteins 0.000 claims 3
• 125000002619 bicyclic group Chemical group 0.000 claims 3
• 150000001875 compounds Chemical class 0.000 claims 3
• 150000005690 diesters Chemical group 0.000 claims 3
• KPUWHANPEXNPJT-UHFFFAOYSA-N disiloxane Chemical compound [SiH3]O[SiH3] KPUWHANPEXNPJT-UHFFFAOYSA-N 0.000 claims 3
• 239000003755 preservative agent Substances 0.000 claims 3
• IIACRCGMVDHOTQ-UHFFFAOYSA-M sulfamate Chemical compound NS([O-])(=O)=O IIACRCGMVDHOTQ-UHFFFAOYSA-M 0.000 claims 3
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims 2
• 102000001493 Cyclophilins Human genes 0.000 claims 2
• 108010068682 Cyclophilins Proteins 0.000 claims 2
• MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims 2
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims 2
• 229920002565 Polyethylene Glycol 400 Polymers 0.000 claims 2
• 239000002202 Polyethylene glycol Substances 0.000 claims 2
• 239000002253 acid Substances 0.000 claims 2
• 239000011248 coating agent Substances 0.000 claims 2
• 238000000576 coating method Methods 0.000 claims 2
• 229910001882 dioxygen Inorganic materials 0.000 claims 2
• 208000030533 eye disease Diseases 0.000 claims 2
• 229910052756 noble gas Inorganic materials 0.000 claims 2
• 229920001223 polyethylene glycol Polymers 0.000 claims 2
• 230000002335 preservative effect Effects 0.000 claims 2
• 231100000331 toxic Toxicity 0.000 claims 2
• 230000002588 toxic effect Effects 0.000 claims 2
• 208000005590 Choroidal Neovascularization Diseases 0.000 claims 1
• 206010060823 Choroidal neovascularisation Diseases 0.000 claims 1
• 206010010744 Conjunctivitis allergic Diseases 0.000 claims 1
• 206010055665 Corneal neovascularisation Diseases 0.000 claims 1
• 206010012689 Diabetic retinopathy Diseases 0.000 claims 1
• 208000003556 Dry Eye Syndromes Diseases 0.000 claims 1
• 206010013774 Dry eye Diseases 0.000 claims 1
• 208000010412 Glaucoma Diseases 0.000 claims 1
• 208000001344 Macular Edema Diseases 0.000 claims 1
• 206010025415 Macular oedema Diseases 0.000 claims 1
• 208000014139 Retinal vascular disease Diseases 0.000 claims 1
• 208000007014 Retinitis pigmentosa Diseases 0.000 claims 1
• 206010052779 Transplant rejections Diseases 0.000 claims 1
• 206010046851 Uveitis Diseases 0.000 claims 1
• 206010064930 age-related macular degeneration Diseases 0.000 claims 1
• 208000002205 allergic conjunctivitis Diseases 0.000 claims 1
• 230000033115 angiogenesis Effects 0.000 claims 1
• 239000003963 antioxidant agent Substances 0.000 claims 1
• 230000003078 antioxidant effect Effects 0.000 claims 1
• 208000024998 atopic conjunctivitis Diseases 0.000 claims 1
• 201000005667 central retinal vein occlusion Diseases 0.000 claims 1
• 201000000159 corneal neovascularization Diseases 0.000 claims 1
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 1
• 208000002780 macular degeneration Diseases 0.000 claims 1
• 201000010230 macular retinal edema Diseases 0.000 claims 1
• 229910052757 nitrogen Inorganic materials 0.000 claims 1
• 229940071643 prefilled syringe Drugs 0.000 claims 1
• 208000004644 retinal vein occlusion Diseases 0.000 claims 1