AU609242B2 - Cyclosporin compositions - Google Patents
Cyclosporin compositions Download PDFInfo
- Publication number
- AU609242B2 AU609242B2 AU28853/89A AU2885389A AU609242B2 AU 609242 B2 AU609242 B2 AU 609242B2 AU 28853/89 A AU28853/89 A AU 28853/89A AU 2885389 A AU2885389 A AU 2885389A AU 609242 B2 AU609242 B2 AU 609242B2
- Authority
- AU
- Australia
- Prior art keywords
- cyclosporin
- acid
- composition according
- glyceride
- fatty 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
Links
- 229930182912 cyclosporin Natural products 0.000 title claims description 92
- PMATZTZNYRCHOR-CGLBZJNRSA-N Cyclosporin A Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O PMATZTZNYRCHOR-CGLBZJNRSA-N 0.000 title claims description 87
- 108010036949 Cyclosporine Proteins 0.000 title claims description 87
- 229930105110 Cyclosporin A Natural products 0.000 title claims description 84
- 229960001265 ciclosporin Drugs 0.000 title claims description 84
- 239000000203 mixture Substances 0.000 title claims description 49
- 235000014113 dietary fatty acids Nutrition 0.000 claims description 41
- 229930195729 fatty acid Natural products 0.000 claims description 41
- 239000000194 fatty acid Substances 0.000 claims description 41
- WWZKQHOCKIZLMA-UHFFFAOYSA-N octanoic acid Chemical compound CCCCCCCC(O)=O WWZKQHOCKIZLMA-UHFFFAOYSA-N 0.000 claims description 36
- 150000004665 fatty acids Chemical class 0.000 claims description 30
- 239000000839 emulsion Substances 0.000 claims description 28
- 229960002446 octanoic acid Drugs 0.000 claims description 18
- 239000005635 Caprylic acid (CAS 124-07-2) Substances 0.000 claims description 17
- 125000005456 glyceride group Chemical group 0.000 claims description 17
- GHVNFZFCNZKVNT-UHFFFAOYSA-N decanoic acid Chemical compound CCCCCCCCCC(O)=O GHVNFZFCNZKVNT-UHFFFAOYSA-N 0.000 claims description 16
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 claims description 14
- 125000004432 carbon atom Chemical group C* 0.000 claims description 9
- 239000005632 Capric acid (CAS 334-48-5) Substances 0.000 claims description 8
- 239000008194 pharmaceutical composition Substances 0.000 claims description 7
- 239000002253 acid Substances 0.000 claims description 5
- OEOIWYCWCDBOPA-UHFFFAOYSA-N 6-methyl-heptanoic acid Chemical compound CC(C)CCCCC(O)=O OEOIWYCWCDBOPA-UHFFFAOYSA-N 0.000 claims description 4
- 239000012736 aqueous medium Substances 0.000 claims description 4
- FGKJLKRYENPLQH-UHFFFAOYSA-N isocaproic acid Chemical compound CC(C)CCC(O)=O FGKJLKRYENPLQH-UHFFFAOYSA-N 0.000 claims description 4
- FBUKVWPVBMHYJY-UHFFFAOYSA-N nonanoic acid Chemical compound CCCCCCCCC(O)=O FBUKVWPVBMHYJY-UHFFFAOYSA-N 0.000 claims description 4
- OBETXYAYXDNJHR-UHFFFAOYSA-N alpha-ethylcaproic acid Natural products CCCCC(CC)C(O)=O OBETXYAYXDNJHR-UHFFFAOYSA-N 0.000 claims description 3
- OBETXYAYXDNJHR-SSDOTTSWSA-M (2r)-2-ethylhexanoate Chemical compound CCCC[C@@H](CC)C([O-])=O OBETXYAYXDNJHR-SSDOTTSWSA-M 0.000 claims description 2
- JNSSVMGPTZYYIW-UHFFFAOYSA-N 2-chloro-6-methyl-1-oxidopyridin-1-ium Chemical compound CC1=CC=CC(Cl)=[N+]1[O-] JNSSVMGPTZYYIW-UHFFFAOYSA-N 0.000 claims description 2
- 239000005643 Pelargonic acid Substances 0.000 claims description 2
- OAOABCKPVCUNKO-UHFFFAOYSA-N isodecanoic acid Natural products CC(C)CCCCCCC(O)=O OAOABCKPVCUNKO-UHFFFAOYSA-N 0.000 claims description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 24
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 21
- 238000002360 preparation method Methods 0.000 description 17
- 239000000243 solution Substances 0.000 description 17
- 239000003921 oil Substances 0.000 description 14
- 235000019198 oils Nutrition 0.000 description 14
- 108010036941 Cyclosporins Proteins 0.000 description 13
- 239000004094 surface-active agent Substances 0.000 description 10
- 238000012360 testing method Methods 0.000 description 10
- 239000002504 physiological saline solution Substances 0.000 description 8
- GHBFNMLVSPCDGN-UHFFFAOYSA-N rac-1-monooctanoylglycerol Chemical compound CCCCCCCC(=O)OCC(O)CO GHBFNMLVSPCDGN-UHFFFAOYSA-N 0.000 description 8
- 239000002904 solvent Substances 0.000 description 8
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 8
- HQPMKSGTIOYHJT-UHFFFAOYSA-N ethane-1,2-diol;propane-1,2-diol Chemical compound OCCO.CC(O)CO HQPMKSGTIOYHJT-UHFFFAOYSA-N 0.000 description 7
- 229920001993 poloxamer 188 Polymers 0.000 description 7
- 239000004359 castor oil Substances 0.000 description 6
- 235000019438 castor oil Nutrition 0.000 description 6
- 238000009472 formulation Methods 0.000 description 6
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 6
- 150000001875 compounds Chemical class 0.000 description 5
- 238000002474 experimental method Methods 0.000 description 5
- 239000002245 particle Substances 0.000 description 5
- 238000000926 separation method Methods 0.000 description 5
- 208000024891 symptom Diseases 0.000 description 5
- 235000019483 Peanut oil Nutrition 0.000 description 4
- 239000004006 olive oil Substances 0.000 description 4
- 235000008390 olive oil Nutrition 0.000 description 4
- 239000000312 peanut oil Substances 0.000 description 4
- 208000011580 syndromic disease Diseases 0.000 description 4
- 150000003626 triacylglycerols Chemical class 0.000 description 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- -1 fatty acid triglycerides Chemical class 0.000 description 3
- 230000001506 immunosuppresive effect Effects 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 210000001519 tissue Anatomy 0.000 description 3
- GEUKOOCPPICVTB-SMOCYEBVSA-N (3s,6s,9s,12r,15s,18s,21s,24s,30s)-33-[(1r,2r)-1-hydroxy-2-methylhexyl]-1,4,7,10,12,15,19,25,28-nonamethyl-6,9,18,24-tetrakis(2-methylpropyl)-3,21,30-tri(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacontane-2,5,8,11,14,17,20,23,26,29,32- Chemical compound CCCC[C@@H](C)[C@@H](O)C1N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C(=O)[C@H](C(C)C)NC1=O GEUKOOCPPICVTB-SMOCYEBVSA-N 0.000 description 2
- JTOKYIBTLUQVQV-QRVTZXGZSA-N (3s,6s,9s,12r,15s,18s,21s,24s,30s,33s)-30-[(1r)-1-hydroxyethyl]-33-[(e,1r,2r)-1-hydroxy-2-methylhex-4-enyl]-1,4,7,10,12,15,19,25,28-nonamethyl-6,9,18,24-tetrakis(2-methylpropyl)-3,21-di(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacontan Chemical compound C\C=C\C[C@@H](C)[C@@H](O)[C@@H]1N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C(=O)[C@H]([C@@H](C)O)NC1=O JTOKYIBTLUQVQV-QRVTZXGZSA-N 0.000 description 2
- PZNPLUBHRSSFHT-RRHRGVEJSA-N 1-hexadecanoyl-2-octadecanoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCCCC(=O)O[C@@H](COP([O-])(=O)OCC[N+](C)(C)C)COC(=O)CCCCCCCCCCCCCCC PZNPLUBHRSSFHT-RRHRGVEJSA-N 0.000 description 2
- MHPUGCYGQWGLJL-UHFFFAOYSA-N 5-methyl-hexanoic acid Chemical compound CC(C)CCCC(O)=O MHPUGCYGQWGLJL-UHFFFAOYSA-N 0.000 description 2
- JTOKYIBTLUQVQV-UHFFFAOYSA-N Cyclosporin C Natural products CC=CCC(C)C(O)C1N(C)C(=O)C(C(C)C)N(C)C(=O)C(CC(C)C)N(C)C(=O)C(CC(C)C)N(C)C(=O)C(C)NC(=O)C(C)NC(=O)C(CC(C)C)N(C)C(=O)C(C(C)C)NC(=O)C(CC(C)C)N(C)C(=O)CN(C)C(=O)C(C(C)O)NC1=O JTOKYIBTLUQVQV-UHFFFAOYSA-N 0.000 description 2
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- ARIWANIATODDMH-UHFFFAOYSA-N Lauric acid monoglyceride Natural products CCCCCCCCCCCC(=O)OCC(O)CO ARIWANIATODDMH-UHFFFAOYSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 210000001124 body fluid Anatomy 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 108010019248 cyclosporin C Proteins 0.000 description 2
- 108010040781 dihydrocyclosporin D Proteins 0.000 description 2
- POULHZVOKOAJMA-UHFFFAOYSA-N dodecanoic acid Chemical compound CCCCCCCCCCCC(O)=O POULHZVOKOAJMA-UHFFFAOYSA-N 0.000 description 2
- 239000003995 emulsifying agent Substances 0.000 description 2
- 239000012530 fluid Substances 0.000 description 2
- MNWFXJYAOYHMED-UHFFFAOYSA-N heptanoic acid Chemical compound CCCCCCC(O)=O MNWFXJYAOYHMED-UHFFFAOYSA-N 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 239000008213 purified water Substances 0.000 description 2
- 238000003127 radioimmunoassay Methods 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000008347 soybean phospholipid Substances 0.000 description 2
- 238000009210 therapy by ultrasound Methods 0.000 description 2
- VLPFTAMPNXLGLX-UHFFFAOYSA-N trioctanoin Chemical compound CCCCCCCC(=O)OCC(OC(=O)CCCCCCC)COC(=O)CCCCCCC VLPFTAMPNXLGLX-UHFFFAOYSA-N 0.000 description 2
- 235000015112 vegetable and seed oil Nutrition 0.000 description 2
- 239000008158 vegetable oil Substances 0.000 description 2
- KILNVBDSWZSGLL-KXQOOQHDSA-N 1,2-dihexadecanoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCCCCCCCCC KILNVBDSWZSGLL-KXQOOQHDSA-N 0.000 description 1
- RZRNAYUHWVFMIP-KTKRTIGZSA-N 1-oleoylglycerol Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC(O)CO RZRNAYUHWVFMIP-KTKRTIGZSA-N 0.000 description 1
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
- 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 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- LKUNXBRZDFMZOK-GFCCVEGCSA-N Capric acid monoglyceride Natural products CCCCCCCCCC(=O)OC[C@H](O)CO LKUNXBRZDFMZOK-GFCCVEGCSA-N 0.000 description 1
- 108010069514 Cyclic Peptides Proteins 0.000 description 1
- 102000001189 Cyclic Peptides Human genes 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- 239000001828 Gelatine Substances 0.000 description 1
- 208000005100 Herpetic Keratitis Diseases 0.000 description 1
- 206010020864 Hypertrichosis Diseases 0.000 description 1
- 239000005639 Lauric acid Substances 0.000 description 1
- 108010038807 Oligopeptides Proteins 0.000 description 1
- 102000015636 Oligopeptides Human genes 0.000 description 1
- 206010073938 Ophthalmic herpes simplex Diseases 0.000 description 1
- 241000283977 Oryctolagus Species 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- HFHDHCJBZVLPGP-RWMJIURBSA-N alpha-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO HFHDHCJBZVLPGP-RWMJIURBSA-N 0.000 description 1
- 125000000539 amino acid group Chemical group 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 230000000843 anti-fungal effect Effects 0.000 description 1
- 230000001741 anti-phlogistic effect Effects 0.000 description 1
- 230000002421 anti-septic effect Effects 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000003125 aqueous solvent Substances 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 210000004240 ciliary body Anatomy 0.000 description 1
- 239000006184 cosolvent Substances 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 235000019961 diglycerides of fatty acid Nutrition 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000004945 emulsification Methods 0.000 description 1
- 230000001804 emulsifying effect Effects 0.000 description 1
- 210000002615 epidermis Anatomy 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 201000010884 herpes simplex virus keratitis Diseases 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- 239000001788 mono and diglycerides of fatty acids Substances 0.000 description 1
- RZRNAYUHWVFMIP-UHFFFAOYSA-N monoelaidin Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC(O)CO RZRNAYUHWVFMIP-UHFFFAOYSA-N 0.000 description 1
- 201000006417 multiple sclerosis Diseases 0.000 description 1
- 231100000344 non-irritating Toxicity 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 239000003002 pH adjusting agent Substances 0.000 description 1
- 239000002304 perfume Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- 229920001281 polyalkylene Polymers 0.000 description 1
- 229920005862 polyol Polymers 0.000 description 1
- 150000003077 polyols Chemical class 0.000 description 1
- 229920002503 polyoxyethylene-polyoxypropylene Polymers 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000012797 qualification Methods 0.000 description 1
- 230000008085 renal dysfunction Effects 0.000 description 1
- 229940063122 sandimmune Drugs 0.000 description 1
- 230000035807 sensation Effects 0.000 description 1
- 239000003549 soybean oil Substances 0.000 description 1
- 235000012424 soybean oil Nutrition 0.000 description 1
- 238000001694 spray drying Methods 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 230000001839 systemic circulation Effects 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 238000005809 transesterification reaction Methods 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 208000018464 vernal keratoconjunctivitis Diseases 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
Classifications
-
- 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
- A61K47/14—Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
- A61K38/12—Cyclic peptides, e.g. bacitracins; Polymyxins; Gramicidins S, C; Tyrocidins A, B or C
- A61K38/13—Cyclosporins
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Dispersion Chemistry (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- General Chemical & Material Sciences (AREA)
- Biophysics (AREA)
- Molecular Biology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Gastroenterology & Hepatology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Immunology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
Applications Claiming Priority (6)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP1912588 | 1988-01-29 | ||
| JP63-19125 | 1988-01-29 | ||
| JP63-111639 | 1988-05-10 | ||
| JP11163988 | 1988-05-10 | ||
| JP63183127A JP2632010B2 (ja) | 1988-01-29 | 1988-07-22 | シクロスポリン製剤 |
| JP63-183127 | 1988-07-22 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| AU2885389A AU2885389A (en) | 1989-08-03 |
| AU609242B2 true AU609242B2 (en) | 1991-04-26 |
Family
ID=27282507
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU28853/89A Expired AU609242B2 (en) | 1988-01-29 | 1989-01-27 | Cyclosporin compositions |
Country Status (8)
| Country | Link |
|---|---|
| US (1) | US4990337A (enExample) |
| EP (1) | EP0327280B1 (enExample) |
| AU (1) | AU609242B2 (enExample) |
| CA (1) | CA1326995C (enExample) |
| DE (1) | DE68900991D1 (enExample) |
| ES (1) | ES2033086T3 (enExample) |
| GR (1) | GR3004611T3 (enExample) |
| HK (1) | HK35697A (enExample) |
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| US7081445B2 (en) * | 1989-02-20 | 2006-07-25 | Novartis Ag | Cyclosporin galenic forms |
| US5294604A (en) * | 1989-12-20 | 1994-03-15 | The Government Of The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Method of treating ocular diseases by periocular administration of cyclosporine A or G |
| ES2119748T3 (es) * | 1990-03-23 | 1998-10-16 | Yoshitomi Pharmaceutical | Composicion farmaceutica que contiene un farmaco ligeramente soluble en agua. |
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| CZ291237B6 (cs) † | 1993-04-20 | 2003-01-15 | Novartis Ag | Farmaceutický přípravek pro orální podání obsahující cyklosporin A |
| DE4322826A1 (de) * | 1993-07-08 | 1995-01-12 | Galenik Labor Freiburg Gmbh | Pharmazeutisches Präparat |
| US20020099067A1 (en) * | 1993-07-08 | 2002-07-25 | Ulrich Posanski | Pharmaceutical compositions for sparingly soluble therapeutic agents |
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| AU715165B2 (en) | 1994-11-03 | 2000-01-20 | Novartis Ag | Novel cyclosporine preparation forms for oral administration of simple composition and high bio-availability, and process for producing them |
| US5824638A (en) * | 1995-05-22 | 1998-10-20 | Shire Laboratories, Inc. | Oral insulin delivery |
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| US5962019A (en) * | 1995-08-25 | 1999-10-05 | Sangstat Medical Corporation | Oral cyclosporin formulations |
| US5827822A (en) * | 1996-03-25 | 1998-10-27 | Sangstat Medical Corporation | Cyclosporin a formulations as nanoparticles |
| US5766629A (en) | 1995-08-25 | 1998-06-16 | Sangstat Medical Corporation | Oral cyclosporin formulations |
| EP0760237A1 (en) * | 1995-08-30 | 1997-03-05 | Cipla Limited | Oil-in-water microemulsions |
| DE19544507B4 (de) | 1995-11-29 | 2007-11-15 | Novartis Ag | Cyclosporin enthaltende Präparate |
| CZ288631B6 (cs) * | 1996-01-18 | 2001-08-15 | Galena, A. S. | Léčivé přípravky s obsahem cyklosporinu |
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| US5660858A (en) * | 1996-04-03 | 1997-08-26 | Research Triangle Pharmaceuticals | Cyclosporin emulsions |
| CN1303985C (zh) | 1996-08-22 | 2007-03-14 | Rtp药品公司 | 含有水不溶性物质微粒的组合物及其制备法 |
| US7255877B2 (en) * | 1996-08-22 | 2007-08-14 | Jagotec Ag | Fenofibrate microparticles |
| US6465016B2 (en) | 1996-08-22 | 2002-10-15 | Research Triangle Pharmaceuticals | Cyclosporiine particles |
| EP0988046B1 (en) | 1997-01-30 | 2004-09-15 | Novartis AG | Oil-free pharmaceutical compositions containing cyclosporin a |
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| US6187747B1 (en) | 1997-09-08 | 2001-02-13 | Panacea Biotech Limited | Pharmaceutical composition comprising cyclosporin |
| US6008191A (en) * | 1997-09-08 | 1999-12-28 | Panacea Biotec Limited | Pharmaceutical compositions containing cyclosporin |
| IN188719B (enExample) * | 1997-09-08 | 2002-11-02 | Panacea Biotec Ltd | |
| US6346511B1 (en) | 1997-09-08 | 2002-02-12 | Panacea Biotec Limited | Pharmaceutical composition comprising cyclosporin |
| JP4761093B2 (ja) | 1997-12-10 | 2011-08-31 | シクロスポリン セラポイティクス リミテッド | オメガ−３脂肪酸油を含む医薬組成物 |
| DE19810655A1 (de) * | 1998-03-12 | 1999-09-16 | Univ Eberhard Karls | Arzneimittel mit einem Gehalt an Ciclosporin |
| US6979456B1 (en) | 1998-04-01 | 2005-12-27 | Jagotec Ag | Anticancer compositions |
| US8415329B1 (en) | 1998-05-29 | 2013-04-09 | Jagotec Ag | Thermoprotected compositions and process for terminal steam sterilization of microparticle preparations |
| EP0976394A1 (en) * | 1998-07-30 | 2000-02-02 | Biosearch Italia S.p.A. | New injectable formulations |
| HUP0105089A3 (en) | 1998-11-20 | 2002-09-30 | Skyepharma Canada Inc | Compositions containing the active ingredient in form dispersible phospholipid stabilized microparticles |
| MXPA01005884A (es) | 1998-12-11 | 2002-04-24 | Pharmasolutions Inc | Composiciones auto-emulsionantes para medicamentos escasamente solubles en agua. |
| US6447806B1 (en) | 1999-02-25 | 2002-09-10 | Novartis Ag | Pharmaceutical compositions comprised of stabilized peptide particles |
| US6057289A (en) * | 1999-04-30 | 2000-05-02 | Pharmasolutions, Inc. | Pharmaceutical composition comprising cyclosporin in association with a carrier in a self-emulsifying drug delivery system |
| IL148685A0 (en) * | 1999-09-21 | 2002-09-12 | Rtp Pharma Inc | Surface modified particulate compositions of biologically active substances |
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| AU2127400A (en) * | 1999-11-02 | 2001-05-14 | Cipla Limited | A pharmaceutical composition for the administration of water-insoluble pharmaceutically active substances and process for preparation thereof |
| US7732404B2 (en) * | 1999-12-30 | 2010-06-08 | Dexcel Ltd | Pro-nanodispersion for the delivery of cyclosporin |
| GB0008785D0 (en) * | 2000-04-10 | 2000-05-31 | Novartis Ag | Organic compounds |
| AU2001255515A1 (en) * | 2000-09-20 | 2002-04-02 | Skyepharma Canada Inc. | Stabilised fibrate microparticles |
| US8586094B2 (en) * | 2000-09-20 | 2013-11-19 | Jagotec Ag | Coated tablets |
| RU2317067C2 (ru) * | 2001-10-19 | 2008-02-20 | Изотехника Инк. | Микроэмульсионный предконцентрат аналога циклоспорина |
| US6979672B2 (en) | 2002-12-20 | 2005-12-27 | Polichem, S.A. | Cyclosporin-based pharmaceutical compositions |
| US20050059583A1 (en) | 2003-09-15 | 2005-03-17 | Allergan, Inc. | Methods of providing therapeutic effects using cyclosporin components |
| US7151085B2 (en) * | 2004-11-15 | 2006-12-19 | Allergan, Inc. | Therapeutic methods using cyclosporine components |
| US7135455B2 (en) * | 2004-11-15 | 2006-11-14 | Allergan, Inc | Methods for the therapeutic use of cyclosporine components |
| PL1885342T3 (pl) | 2005-03-21 | 2016-10-31 | Inhibitor krystalizacji i jego zastosowanie w kapsułkach żelatynowych | |
| GB2451811A (en) | 2007-08-09 | 2009-02-18 | Ems Sa | Delivery composition for solubilising water-insoluble pharmaceutical active ingredients |
| TR201909840T4 (tr) | 2011-03-11 | 2019-07-22 | Beth Israel Deaconess Medical Ct Inc | Anti-CD40 antikorları ve kullanımları. |
| EP3197865A1 (en) | 2014-09-26 | 2017-08-02 | The Chemours Company FC, LLC | Sulfonated fluorinated, non-fluorinated or partially fluorinated urethanes |
| JP6976931B2 (ja) | 2015-09-04 | 2021-12-08 | プリマトープ・セラピューティクス・インコーポレイテッド | ヒト化抗ｃｄ４０抗体及びその使用 |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE149197C (enExample) * | 1902-10-24 | |||
| US2865859A (en) * | 1956-11-09 | 1958-12-23 | Irwin I Lubowe | Solubilizing of mineral, vegetable, animal oils for cosmetic, pharmaceutical and industrial purposes |
| US3678149A (en) * | 1970-01-26 | 1972-07-18 | Samuel J Prigal | Method of enhancing the action of a medicament |
| FI65914C (fi) * | 1978-03-07 | 1984-08-10 | Sandoz Ag | Foerfarande foer framstaellning av farmaceutiska kompositionerinnehaollande cyklosporin a |
| CH641356A5 (en) * | 1979-02-27 | 1984-02-29 | Sandoz Ag | Pharmaceutical compositions containing cyclosporin |
| JPS5921613A (ja) * | 1982-07-28 | 1984-02-03 | Takeda Chem Ind Ltd | 直腸投与製剤 |
| DE3372705D1 (en) * | 1982-04-30 | 1987-09-03 | Takeda Chemical Industries Ltd | Pharmaceutical composition and its use |
| US4659696A (en) * | 1982-04-30 | 1987-04-21 | Takeda Chemical Industries, Ltd. | Pharmaceutical composition and its nasal or vaginal use |
| US4474751A (en) * | 1983-05-16 | 1984-10-02 | Merck & Co., Inc. | Ophthalmic drug delivery system utilizing thermosetting gels |
| BE897724A (fr) * | 1983-09-09 | 1984-01-02 | Mallien Denis | Systeme de communication selective, bidirectionnelle, par radio, entre un poste de commande et plusieurs postes de travail |
| DE3339236A1 (de) * | 1983-10-28 | 1985-05-09 | Bayer Ag | Arzneimittelzubereitung |
| US4612193A (en) * | 1983-12-23 | 1986-09-16 | Del Laboratories, Inc. | Sty ointment and method of using the same |
| US4722914A (en) * | 1984-05-30 | 1988-02-02 | Motorola Inc. | Method of making a high density IC module assembly |
| EP0170623B1 (en) * | 1984-08-02 | 1990-11-28 | Sandoz Ag | Novel pharmaceutical use of (nva)2-cyclosporine |
| US4649047A (en) * | 1985-03-19 | 1987-03-10 | University Of Georgia Research Foundation, Inc. | Ophthalmic treatment by topical administration of cyclosporin |
| US4839342A (en) * | 1987-09-03 | 1989-06-13 | University Of Georgia Research Foundation, Inc. | Method of increasing tear production by topical administration of cyclosporin |
-
1989
- 1989-01-27 EP EP89300856A patent/EP0327280B1/en not_active Expired
- 1989-01-27 CA CA000589378A patent/CA1326995C/en not_active Expired - Lifetime
- 1989-01-27 DE DE8989300856T patent/DE68900991D1/de not_active Expired - Lifetime
- 1989-01-27 AU AU28853/89A patent/AU609242B2/en not_active Expired
- 1989-01-27 ES ES198989300856T patent/ES2033086T3/es not_active Expired - Lifetime
-
1990
- 1990-04-12 US US07/511,992 patent/US4990337A/en not_active Expired - Lifetime
-
1992
- 1992-05-18 GR GR920400935T patent/GR3004611T3/el unknown
-
1997
- 1997-03-20 HK HK35697A patent/HK35697A/en not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| DE68900991D1 (de) | 1992-04-23 |
| AU2885389A (en) | 1989-08-03 |
| GR3004611T3 (enExample) | 1993-04-28 |
| ES2033086T3 (es) | 1993-03-01 |
| EP0327280A1 (en) | 1989-08-09 |
| US4990337A (en) | 1991-02-05 |
| HK35697A (en) | 1997-03-27 |
| CA1326995C (en) | 1994-02-15 |
| EP0327280B1 (en) | 1992-03-18 |
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Legal Events
| Date | Code | Title | Description |
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| PC | Assignment registered |
Owner name: NOVARTIS AG Free format text: FORMER OWNER WAS: SANKYO COMPANY LIMITED |