JPH0338280B2 - - Google Patents

Info

Publication number: JPH0338280B2
Authority: JP; Japan
Prior art keywords: cyclosporin; ser; meleu; residue; formula
Prior art date: 1981-01-09
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.): Expired - Lifetime

Application number

JP57002187A

Other languages

English (en)

Japanese (ja)

Other versions

JPS57140753A (en

Inventor

Boringeru Piitoro

Yakobu Berushuteruri Yohan

Kooberu Hansu

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Sandoz AG

Original Assignee

Sandoz AG

Priority date (The priority date 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 date listed.)

1981-01-09

Filing date

1982-01-08

Publication date

1991-06-10

1982-01-08 Application filed by Sandoz AG filed Critical Sandoz AG

1982-08-31 Publication of JPS57140753A publication Critical patent/JPS57140753A/ja

1991-06-10 Publication of JPH0338280B2 publication Critical patent/JPH0338280B2/ja

Status Granted legal-status Critical Current

Links

229960001265 ciclosporin Drugs 0.000 claims description 67
229930182912 cyclosporin Natural products 0.000 claims description 62
108010036949 Cyclosporine Proteins 0.000 claims description 53
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 claims description 52
229930105110 Cyclosporin A Natural products 0.000 claims description 40
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 7
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 6
125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 6
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
239000004480 active ingredient Substances 0.000 claims description 3
229960003444 immunosuppressant agent Drugs 0.000 claims description 2
230000001861 immunosuppressant effect Effects 0.000 claims description 2
239000003018 immunosuppressive agent Substances 0.000 claims description 2
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 51
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 45
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 24
239000000203 mixture Substances 0.000 description 22
238000000034 method Methods 0.000 description 21
239000000243 solution Substances 0.000 description 16
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 15
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 15
108010036941 Cyclosporins Proteins 0.000 description 14
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 11
239000000047 product Substances 0.000 description 11
239000000741 silica gel Substances 0.000 description 11
229910002027 silica gel Inorganic materials 0.000 description 11
150000001875 compounds Chemical class 0.000 description 10
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
239000007788 liquid Substances 0.000 description 9
238000004519 manufacturing process Methods 0.000 description 9
239000003480 eluent Substances 0.000 description 8
108090000765 processed proteins & peptides Proteins 0.000 description 8
239000002904 solvent Substances 0.000 description 8
238000004587 chromatography analysis Methods 0.000 description 7
125000004430 oxygen atom Chemical group O* 0.000 description 7
239000008194 pharmaceutical composition Substances 0.000 description 7
239000002609 medium Substances 0.000 description 6
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 5
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 5
230000003110 anti-inflammatory effect Effects 0.000 description 5
239000000284 extract Substances 0.000 description 5
238000005984 hydrogenation reaction Methods 0.000 description 5
238000010189 synthetic method Methods 0.000 description 5
238000012360 testing method Methods 0.000 description 5
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
206010003246 arthritis Diseases 0.000 description 4
230000015572 biosynthetic process Effects 0.000 description 4
239000002285 corn oil Substances 0.000 description 4
235000005687 corn oil Nutrition 0.000 description 4
-1 cyclosporins A Natural products 0.000 description 4
238000000855 fermentation Methods 0.000 description 4
230000004151 fermentation Effects 0.000 description 4
239000001963 growth medium Substances 0.000 description 4
230000001506 immunosuppresive effect Effects 0.000 description 4
239000004615 ingredient Substances 0.000 description 4
235000015097 nutrients Nutrition 0.000 description 4
239000004006 olive oil Substances 0.000 description 4
235000008390 olive oil Nutrition 0.000 description 4
125000006239 protecting group Chemical group 0.000 description 4
239000011734 sodium Substances 0.000 description 4
238000003786 synthesis reaction Methods 0.000 description 4
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
241000894006 Bacteria Species 0.000 description 3
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
150000001413 amino acids Chemical class 0.000 description 3
239000008346 aqueous phase Substances 0.000 description 3
238000007385 chemical modification Methods 0.000 description 3
150000002148 esters Chemical class 0.000 description 3
210000004698 lymphocyte Anatomy 0.000 description 3
239000012074 organic phase Substances 0.000 description 3
239000011541 reaction mixture Substances 0.000 description 3
239000000725 suspension Substances 0.000 description 3
235000015112 vegetable and seed oil Nutrition 0.000 description 3
239000008158 vegetable oil Substances 0.000 description 3
229920001817 Agar Polymers 0.000 description 2
239000001715 Ammonium malate Substances 0.000 description 2
MTCFGRXMJLQNBG-UWTATZPHSA-N D-Serine Chemical compound OC[C@@H](N)C(O)=O MTCFGRXMJLQNBG-UWTATZPHSA-N 0.000 description 2
229930195711 D-Serine Natural products 0.000 description 2
WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
241000700159 Rattus Species 0.000 description 2
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 description 2
239000008272 agar Substances 0.000 description 2
125000000539 amino acid group Chemical group 0.000 description 2
KGECWXXIGSTYSQ-UHFFFAOYSA-N ammonium malate Chemical compound [NH4+].[NH4+].[O-]C(=O)C(O)CC([O-])=O KGECWXXIGSTYSQ-UHFFFAOYSA-N 0.000 description 2
235000019292 ammonium malate Nutrition 0.000 description 2
239000007864 aqueous solution Substances 0.000 description 2
238000007796 conventional method Methods 0.000 description 2
239000003814 drug Substances 0.000 description 2
238000009472 formulation Methods 0.000 description 2
239000011521 glass Substances 0.000 description 2
239000008103 glucose Substances 0.000 description 2
125000005456 glyceride group Chemical group 0.000 description 2
238000000227 grinding Methods 0.000 description 2
230000005764 inhibitory process Effects 0.000 description 2
230000002906 microbiologic effect Effects 0.000 description 2
239000003921 oil Substances 0.000 description 2
235000019198 oils Nutrition 0.000 description 2
239000002245 particle Substances 0.000 description 2
239000000546 pharmaceutical excipient Substances 0.000 description 2
229940124531 pharmaceutical excipient Drugs 0.000 description 2
230000000144 pharmacologic effect Effects 0.000 description 2
BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
239000002243 precursor Substances 0.000 description 2
238000007363 ring formation reaction Methods 0.000 description 2
229920006395 saturated elastomer Polymers 0.000 description 2
238000000926 separation method Methods 0.000 description 2
235000017557 sodium bicarbonate Nutrition 0.000 description 2
235000002639 sodium chloride Nutrition 0.000 description 2
239000011780 sodium chloride Substances 0.000 description 2
229910052938 sodium sulfate Inorganic materials 0.000 description 2
235000011152 sodium sulphate Nutrition 0.000 description 2
239000007787 solid Substances 0.000 description 2
230000003381 solubilizing effect Effects 0.000 description 2
238000003756 stirring Methods 0.000 description 2
239000013589 supplement Substances 0.000 description 2
230000001225 therapeutic effect Effects 0.000 description 2
238000006257 total synthesis reaction Methods 0.000 description 2
238000005809 transesterification reaction Methods 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 1
TYFOVYYNQGNDKH-KCLVVAEESA-N (3s,6s,9s,12r,15s,18s,21s,24s,30s,33s)-30-ethyl-33-[(1r)-1-hydroxy-2-methylhexyl]-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-undecazacyclotritriacontane-2,5,8,11,14,17,20,23,26, Chemical compound CCCCC(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](CC)NC1=O TYFOVYYNQGNDKH-KCLVVAEESA-N 0.000 description 1
UCOQITKXMNKTKF-MXGZYYNMSA-N (3s,6s,9s,12r,15s,18s,21s,24s,30s,33s)-33-[(e,1r,2r)-1-hydroxy-2-methylhex-4-enyl]-1,4,7,10,12,15,19,25,28,30-decamethyl-6,9,18,24-tetrakis(2-methylpropyl)-3,21-di(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacontane-2,5,8,11,14,17,20,23 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)NC1=O UCOQITKXMNKTKF-MXGZYYNMSA-N 0.000 description 1
ZNVBEWJRWHNZMK-SYOLRUPNSA-N (3s,6s,9s,12r,15s,18s,21s,24s,30s,33s)-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)-3,21,30-tri(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacontane-2,5,8,11,14,17,20,2 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(C)C)NC1=O ZNVBEWJRWHNZMK-SYOLRUPNSA-N 0.000 description 1
ZMKGDQSIRSGUDJ-VSROPUKISA-N (3s,6s,9s,12r,15s,18s,21s,24s,30s,33s)-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)-30-propyl-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacontane-2,5,8,11,14,1 Chemical compound CCC[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 ZMKGDQSIRSGUDJ-VSROPUKISA-N 0.000 description 1
AZUYLZMQTIKGSC-UHFFFAOYSA-N 1-[6-[4-(5-chloro-6-methyl-1H-indazol-4-yl)-5-methyl-3-(1-methylindazol-5-yl)pyrazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]prop-2-en-1-one Chemical compound ClC=1C(=C2C=NNC2=CC=1C)C=1C(=NN(C=1C)C1CC2(CN(C2)C(C=C)=O)C1)C=1C=C2C=NN(C2=CC=1)C AZUYLZMQTIKGSC-UHFFFAOYSA-N 0.000 description 1
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
235000019489 Almond oil Nutrition 0.000 description 1
208000023275 Autoimmune disease Diseases 0.000 description 1
DWRXFEITVBNRMK-UHFFFAOYSA-N Beta-D-1-Arabinofuranosylthymine Natural products O=C1NC(=O)C(C)=CN1C1C(O)C(O)C(CO)O1 DWRXFEITVBNRMK-UHFFFAOYSA-N 0.000 description 1
UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
108010062580 Concanavalin A Proteins 0.000 description 1
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 1
206010018910 Haemolysis Diseases 0.000 description 1
SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 1
238000005481 NMR spectroscopy Methods 0.000 description 1
ZMKGDQSIRSGUDJ-UHFFFAOYSA-N NVa2 cyclosporine Natural products CCCC1NC(=O)C(C(O)C(C)CC=CC)N(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)C1=O ZMKGDQSIRSGUDJ-UHFFFAOYSA-N 0.000 description 1
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LFYJSSARVMHQJB-QIXNEVBVSA-N bakuchiol Chemical compound CC(C)=CCC[C@@](C)(C=C)\C=C\C1=CC=C(O)C=C1 LFYJSSARVMHQJB-QIXNEVBVSA-N 0.000 description 1
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239000000543 intermediate Substances 0.000 description 1
229910052740 iodine Inorganic materials 0.000 description 1
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210000003734 kidney Anatomy 0.000 description 1
229910052943 magnesium sulfate Inorganic materials 0.000 description 1
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125000002950 monocyclic group Chemical group 0.000 description 1
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230000007935 neutral effect Effects 0.000 description 1
125000004433 nitrogen atom Chemical group N* 0.000 description 1
229940049964 oleate Drugs 0.000 description 1
ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
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229920001281 polyalkylene Polymers 0.000 description 1
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229920000573 polyethylene Polymers 0.000 description 1
229920001223 polyethylene glycol Polymers 0.000 description 1
229920005862 polyol Polymers 0.000 description 1
150000003077 polyols Chemical class 0.000 description 1
238000002360 preparation method Methods 0.000 description 1
238000004321 preservation Methods 0.000 description 1
230000002265 prevention Effects 0.000 description 1
230000035755 proliferation Effects 0.000 description 1
230000000069 prophylactic effect Effects 0.000 description 1
238000000746 purification Methods 0.000 description 1
238000001953 recrystallisation Methods 0.000 description 1
238000011160 research Methods 0.000 description 1
238000012827 research and development Methods 0.000 description 1
210000003491 skin Anatomy 0.000 description 1
229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
241000894007 species Species 0.000 description 1
230000003393 splenic effect Effects 0.000 description 1
230000000638 stimulation Effects 0.000 description 1
239000000454 talc Substances 0.000 description 1
229910052623 talc Inorganic materials 0.000 description 1
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
229940104230 thymidine Drugs 0.000 description 1
230000001988 toxicity Effects 0.000 description 1
231100000419 toxicity Toxicity 0.000 description 1
150000003626 triacylglycerols Chemical class 0.000 description 1
UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 1
239000012138 yeast extract Substances 0.000 description 1

Landscapes

Peptides Or Proteins (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

JP57002187A 1981-01-09 1982-01-08 Novel cyclosporine Granted JPS57140753A (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
GB8100566		1981-01-09

Publications (2)

Publication Number	Publication Date
JPS57140753A JPS57140753A (en)	1982-08-31
JPH0338280B2 true JPH0338280B2 (sh)	1991-06-10

Family

ID=10518881

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
JP57002187A Granted JPS57140753A (en)	1981-01-09	1982-01-08	Novel cyclosporine

Country Status (1)

Country	Link
JP (1)	JPS57140753A (sh)

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
CH667274A5 (de) *	1984-03-23	1988-09-30	Sandoz Ag	Cyclosporine, ihre herstellung und diese enthaltende pharmazeutische zusammensetzungen.
CA2518265A1 (en) *	2003-03-17	2004-09-30	Albany Molecular Research, Inc.	Novel cyclosporins
US7361636B2 (en) *	2004-10-06	2008-04-22	Amr Technology, Inc.	Cyclosporin alkynes and their utility as pharmaceutical agents

1982
- 1982-01-08 JP JP57002187A patent/JPS57140753A/ja active Granted

Also Published As

Publication number	Publication date
JPS57140753A (en)	1982-08-31

Publication	Publication Date	Title
EP0056782B1 (en)	1984-08-01	Novel cyclosporins
CA1247546A (en)	1988-12-28	Cyclosporins
US4764503A (en)	1988-08-16	Novel cyclosporins
AU649277B2 (en)	1994-05-19	Improvements in or relating to organic compounds
US5284826A (en)	1994-02-08	0-hydroxyethyl and acyloxyethyl derivatives of [ser]8 cyclosporins
CA1129359A (en)	1982-08-10	Cyclosporin derivatives, their production and pharmaceutical compositions containing them
US4914188A (en)	1990-04-03	Novel 6-position cyclosporin analogs as non-immunosuppressive antagonists of cyclosporin binding to cyclophilin
EP0414632B1 (en)	1996-10-23	Cyclosporin derivatives
JPH0338280B2 (sh)	1991-06-10
GB2227244A (en)	1990-07-25	Immunosuppressive fluorinated cyclosporin analogs
AU596071B2 (en)	1990-04-26	Novel cyclosporins
JPH02184699A (ja)	1990-07-19	“８−アミノ酸”に改良のある新規シクロスポリン誘導体