RU2185188C2 - Фармацевтические композиции - Google Patents
Фармацевтические композиции Download PDFInfo
- Publication number
- RU2185188C2 RU2185188C2 RU99121398/14A RU99121398A RU2185188C2 RU 2185188 C2 RU2185188 C2 RU 2185188C2 RU 99121398/14 A RU99121398/14 A RU 99121398/14A RU 99121398 A RU99121398 A RU 99121398A RU 2185188 C2 RU2185188 C2 RU 2185188C2
- Authority
- RU
- Russia
- Prior art keywords
- fatty acid
- cyclosporin
- drug according
- capsule
- present
- Prior art date
Links
- 239000008194 pharmaceutical composition Substances 0.000 title 1
- 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 abstract description 80
- 108010036949 Cyclosporine Proteins 0.000 claims abstract description 80
- 239000000203 mixture Substances 0.000 claims abstract description 79
- 229960001265 ciclosporin Drugs 0.000 claims abstract description 73
- 229930182912 cyclosporin Natural products 0.000 claims abstract description 71
- 229930105110 Cyclosporin A Natural products 0.000 claims abstract description 59
- 238000002360 preparation method Methods 0.000 claims abstract description 42
- 239000003814 drug Substances 0.000 claims abstract description 33
- 235000014113 dietary fatty acids Nutrition 0.000 claims abstract description 29
- 239000000194 fatty acid Substances 0.000 claims abstract description 29
- 229930195729 fatty acid Natural products 0.000 claims abstract description 29
- 239000004094 surface-active agent Substances 0.000 claims abstract description 29
- RUOJZAUFBMNUDX-UHFFFAOYSA-N propylene carbonate Chemical compound CC1COC(=O)O1 RUOJZAUFBMNUDX-UHFFFAOYSA-N 0.000 claims abstract description 18
- 150000004665 fatty acids Chemical class 0.000 claims abstract description 17
- 239000000126 substance Substances 0.000 claims abstract description 14
- 150000001875 compounds Chemical class 0.000 claims abstract description 13
- 239000000314 lubricant Substances 0.000 claims abstract description 13
- LDVVTQMJQSCDMK-UHFFFAOYSA-N 1,3-dihydroxypropan-2-yl formate Chemical compound OCC(CO)OC=O LDVVTQMJQSCDMK-UHFFFAOYSA-N 0.000 claims abstract description 11
- 150000003138 primary alcohols Chemical class 0.000 claims abstract description 9
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 claims abstract description 9
- 150000002148 esters Chemical class 0.000 claims abstract description 3
- 239000002775 capsule Substances 0.000 claims description 57
- 229940079593 drug Drugs 0.000 claims description 32
- 239000002202 Polyethylene glycol Substances 0.000 claims description 25
- 229920001223 polyethylene glycol Polymers 0.000 claims description 25
- -1 fatty acid ester Chemical class 0.000 claims description 17
- 239000013543 active substance Substances 0.000 claims description 11
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical group C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 claims description 8
- 150000004667 medium chain fatty acids Chemical class 0.000 claims description 5
- XZIIFPSPUDAGJM-UHFFFAOYSA-N 6-chloro-2-n,2-n-diethylpyrimidine-2,4-diamine Chemical compound CCN(CC)C1=NC(N)=CC(Cl)=N1 XZIIFPSPUDAGJM-UHFFFAOYSA-N 0.000 claims description 4
- 239000004359 castor oil Substances 0.000 claims description 4
- 235000019438 castor oil Nutrition 0.000 claims description 4
- 238000000576 coating method Methods 0.000 claims description 4
- 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 claims description 4
- 229940035044 sorbitan monolaurate Drugs 0.000 claims description 4
- 229920001214 Polysorbate 60 Polymers 0.000 claims description 3
- 239000011248 coating agent Substances 0.000 claims description 3
- RZRNAYUHWVFMIP-KTKRTIGZSA-N 1-oleoylglycerol Chemical group CCCCCCCC\C=C/CCCCCCCC(=O)OCC(O)CO RZRNAYUHWVFMIP-KTKRTIGZSA-N 0.000 claims description 2
- 229920003171 Poly (ethylene oxide) Polymers 0.000 claims description 2
- 239000008172 hydrogenated vegetable oil Substances 0.000 claims description 2
- RZRNAYUHWVFMIP-UHFFFAOYSA-N monoelaidin Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC(O)CO RZRNAYUHWVFMIP-UHFFFAOYSA-N 0.000 claims description 2
- FBUKVWPVBMHYJY-UHFFFAOYSA-N nonanoic acid Chemical compound CCCCCCCCC(O)=O FBUKVWPVBMHYJY-UHFFFAOYSA-N 0.000 claims description 2
- 238000003860 storage Methods 0.000 abstract description 9
- 230000000694 effects Effects 0.000 abstract description 5
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 34
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 31
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 30
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 18
- 238000001816 cooling Methods 0.000 description 16
- 239000004014 plasticizer Substances 0.000 description 14
- 235000011187 glycerol Nutrition 0.000 description 13
- 108010010803 Gelatin Proteins 0.000 description 12
- 239000000839 emulsion Substances 0.000 description 12
- 239000008273 gelatin Substances 0.000 description 12
- 229920000159 gelatin Polymers 0.000 description 12
- 235000019322 gelatine Nutrition 0.000 description 12
- 235000011852 gelatine desserts Nutrition 0.000 description 12
- 238000004519 manufacturing process Methods 0.000 description 10
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- 239000007901 soft capsule Substances 0.000 description 9
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
- 239000000047 product Substances 0.000 description 8
- 241000283973 Oryctolagus cuniculus Species 0.000 description 7
- 230000008859 change Effects 0.000 description 7
- 239000012141 concentrate Substances 0.000 description 6
- 239000007903 gelatin capsule Substances 0.000 description 6
- 238000000034 method Methods 0.000 description 6
- 230000035515 penetration Effects 0.000 description 6
- 238000004513 sizing Methods 0.000 description 6
- 239000007788 liquid Substances 0.000 description 5
- 239000000654 additive Substances 0.000 description 4
- 238000009835 boiling Methods 0.000 description 4
- 125000004432 carbon atom Chemical group C* 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 239000008280 blood Substances 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- GVJHHUAWPYXKBD-UHFFFAOYSA-N d-alpha-tocopherol Natural products OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 3
- 238000005538 encapsulation Methods 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- 238000002054 transplantation Methods 0.000 description 3
- 235000015112 vegetable and seed oil Nutrition 0.000 description 3
- 239000008158 vegetable oil Substances 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 108010069514 Cyclic Peptides Proteins 0.000 description 2
- 102000001189 Cyclic Peptides Human genes 0.000 description 2
- 229920001213 Polysorbate 20 Polymers 0.000 description 2
- 150000001413 amino acids Chemical class 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- 230000003110 anti-inflammatory effect Effects 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- FMMOOAYVCKXGMF-MURFETPASA-N ethyl linoleate Chemical compound CCCCC\C=C/C\C=C/CCCCCCCC(=O)OCC FMMOOAYVCKXGMF-MURFETPASA-N 0.000 description 2
- 229940031016 ethyl linoleate Drugs 0.000 description 2
- 230000001506 immunosuppresive effect Effects 0.000 description 2
- FMMOOAYVCKXGMF-UHFFFAOYSA-N linoleic acid ethyl ester Natural products CCCCCC=CCC=CCCCCCCCC(=O)OCC FMMOOAYVCKXGMF-UHFFFAOYSA-N 0.000 description 2
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 2
- 210000000056 organ Anatomy 0.000 description 2
- 239000002957 persistent organic pollutant Substances 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 229940113115 polyethylene glycol 200 Drugs 0.000 description 2
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 2
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 2
- 229920000136 polysorbate Polymers 0.000 description 2
- 238000001556 precipitation Methods 0.000 description 2
- 239000008213 purified water Substances 0.000 description 2
- 150000004671 saturated fatty acids Chemical class 0.000 description 2
- 238000007789 sealing Methods 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- 210000003462 vein Anatomy 0.000 description 2
- 239000003643 water by type Substances 0.000 description 2
- MEJYDZQQVZJMPP-ULAWRXDQSA-N (3s,3ar,6r,6ar)-3,6-dimethoxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan Chemical compound CO[C@H]1CO[C@@H]2[C@H](OC)CO[C@@H]21 MEJYDZQQVZJMPP-ULAWRXDQSA-N 0.000 description 1
- 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
- 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
- CYSGHNMQYZDMIA-UHFFFAOYSA-N 1,3-Dimethyl-2-imidazolidinon Chemical compound CN1CCN(C)C1=O CYSGHNMQYZDMIA-UHFFFAOYSA-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
- JNODDICFTDYODH-UHFFFAOYSA-N 2-hydroxytetrahydrofuran Chemical compound OC1CCCO1 JNODDICFTDYODH-UHFFFAOYSA-N 0.000 description 1
- HIQIXEFWDLTDED-UHFFFAOYSA-N 4-hydroxy-1-piperidin-4-ylpyrrolidin-2-one Chemical compound O=C1CC(O)CN1C1CCNCC1 HIQIXEFWDLTDED-UHFFFAOYSA-N 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N 4-hydroxybenzoic acid Chemical compound OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 208000023275 Autoimmune disease Diseases 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 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 description 1
- 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 description 1
- LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 1
- OYHQOLUKZRVURQ-HZJYTTRNSA-N Linoleic acid Chemical compound CCCCC\C=C/C\C=C/CCCCCCCC(O)=O OYHQOLUKZRVURQ-HZJYTTRNSA-N 0.000 description 1
- 206010025476 Malabsorption Diseases 0.000 description 1
- 208000004155 Malabsorption Syndromes Diseases 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 206010029155 Nephropathy toxic Diseases 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- 229920000604 Polyethylene Glycol 200 Polymers 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical class O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 229910000831 Steel Inorganic materials 0.000 description 1
- 229930003427 Vitamin E Natural products 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000006978 adaptation Effects 0.000 description 1
- VRAIHTAYLFXSJJ-UHFFFAOYSA-N alumane Chemical compound [AlH3].[AlH3] VRAIHTAYLFXSJJ-UHFFFAOYSA-N 0.000 description 1
- 208000007502 anemia Diseases 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 206010003246 arthritis Diseases 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 210000001185 bone marrow Anatomy 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 210000004087 cornea Anatomy 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- XXJWXESWEXIICW-UHFFFAOYSA-N diethylene glycol monoethyl ether Chemical compound CCOCCOCCO XXJWXESWEXIICW-UHFFFAOYSA-N 0.000 description 1
- 229940075557 diethylene glycol monoethyl ether Drugs 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 230000035622 drinking Effects 0.000 description 1
- 230000001804 emulsifying effect Effects 0.000 description 1
- 210000003238 esophagus Anatomy 0.000 description 1
- LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
- 229940093471 ethyl oleate Drugs 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 210000004907 gland Anatomy 0.000 description 1
- 210000002216 heart Anatomy 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 208000014951 hematologic disease Diseases 0.000 description 1
- 229960002897 heparin Drugs 0.000 description 1
- 229920000669 heparin Polymers 0.000 description 1
- TZMQHOJDDMFGQX-UHFFFAOYSA-N hexane-1,1,1-triol Chemical compound CCCCCC(O)(O)O TZMQHOJDDMFGQX-UHFFFAOYSA-N 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 230000008105 immune reaction Effects 0.000 description 1
- 208000027866 inflammatory disease Diseases 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 229940074928 isopropyl myristate Drugs 0.000 description 1
- XUGNVMKQXJXZCD-UHFFFAOYSA-N isopropyl palmitate Chemical compound CCCCCCCCCCCCCCCC(=O)OC(C)C XUGNVMKQXJXZCD-UHFFFAOYSA-N 0.000 description 1
- 229940075495 isopropyl palmitate Drugs 0.000 description 1
- 210000003734 kidney Anatomy 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
- 235000020778 linoleic acid Nutrition 0.000 description 1
- OYHQOLUKZRVURQ-IXWMQOLASA-N linoleic acid Natural products CCCCC\C=C/C\C=C\CCCCCCCC(O)=O OYHQOLUKZRVURQ-IXWMQOLASA-N 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 201000004792 malaria Diseases 0.000 description 1
- 239000001525 mentha piperita l. herb oil Substances 0.000 description 1
- 239000004530 micro-emulsion Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 230000007694 nephrotoxicity Effects 0.000 description 1
- 231100000417 nephrotoxicity Toxicity 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- WWZKQHOCKIZLMA-UHFFFAOYSA-N octanoic acid Chemical compound CCCCCCCC(O)=O WWZKQHOCKIZLMA-UHFFFAOYSA-N 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 239000005022 packaging material Substances 0.000 description 1
- 235000019477 peppermint oil Nutrition 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 235000019271 petrolatum Nutrition 0.000 description 1
- 229940124531 pharmaceutical excipient Drugs 0.000 description 1
- 239000008180 pharmaceutical surfactant Substances 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
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 229940063122 sandimmune Drugs 0.000 description 1
- 201000004409 schistosomiasis Diseases 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 210000003491 skin Anatomy 0.000 description 1
- 239000007886 soft shell capsule Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 230000003595 spectral effect Effects 0.000 description 1
- 239000010959 steel Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000004781 supercooling Methods 0.000 description 1
- 201000000596 systemic lupus erythematosus Diseases 0.000 description 1
- 229930003799 tocopherol Natural products 0.000 description 1
- 235000010384 tocopherol Nutrition 0.000 description 1
- 229960001295 tocopherol Drugs 0.000 description 1
- 239000011732 tocopherol Substances 0.000 description 1
- 238000005809 transesterification reaction Methods 0.000 description 1
- 150000003626 triacylglycerols Chemical class 0.000 description 1
- LADGBHLMCUINGV-UHFFFAOYSA-N tricaprin Chemical compound CCCCCCCCCC(=O)OCC(OC(=O)CCCCCCCCC)COC(=O)CCCCCCCCC LADGBHLMCUINGV-UHFFFAOYSA-N 0.000 description 1
- 235000019165 vitamin E Nutrition 0.000 description 1
- 239000011709 vitamin E Substances 0.000 description 1
- 229940046009 vitamin E Drugs 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
- GVJHHUAWPYXKBD-IEOSBIPESA-N α-tocopherol Chemical compound OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 0.000 description 1
Images
Classifications
-
- 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
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
-
- 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
-
- 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
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/4841—Filling excipients; Inactive ingredients
- A61K9/4858—Organic compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Immunology (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Transplantation (AREA)
- Molecular Biology (AREA)
- Dispersion Chemistry (AREA)
- Biophysics (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Gastroenterology & Hepatology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR1997/8750 | 1997-03-14 | ||
| KR1019970008750A KR19980073479A (ko) | 1997-03-14 | 1997-03-14 | 사이클로스포린-함유 연질캅셀제 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| RU99121398A RU99121398A (ru) | 2001-12-27 |
| RU2185188C2 true RU2185188C2 (ru) | 2002-07-20 |
Family
ID=19499792
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| RU99121398/14A RU2185188C2 (ru) | 1997-03-14 | 1998-03-12 | Фармацевтические композиции |
Country Status (24)
| Country | Link |
|---|---|
| EP (1) | EP0969857A1 (cs) |
| JP (1) | JP3748573B2 (cs) |
| KR (2) | KR19980073479A (cs) |
| CN (1) | CN1161150C (cs) |
| AR (1) | AR012054A1 (cs) |
| AU (1) | AU741923B2 (cs) |
| BR (1) | BR9808324A (cs) |
| CA (1) | CA2283901A1 (cs) |
| CO (1) | CO4940404A1 (cs) |
| CZ (1) | CZ324399A3 (cs) |
| DE (1) | DE19882184T1 (cs) |
| GB (1) | GB2337703A (cs) |
| HU (1) | HUP0001515A3 (cs) |
| ID (1) | ID23531A (cs) |
| IL (1) | IL131703A0 (cs) |
| MY (1) | MY118614A (cs) |
| NO (1) | NO994436L (cs) |
| PE (1) | PE59499A1 (cs) |
| PL (1) | PL335729A1 (cs) |
| RU (1) | RU2185188C2 (cs) |
| SK (1) | SK123299A3 (cs) |
| TR (1) | TR199902229T2 (cs) |
| WO (1) | WO1998041225A1 (cs) |
| ZA (1) | ZA982117B (cs) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB2380674B (en) * | 1998-03-06 | 2003-05-28 | Novartis Ag | Emulsion preconcentrates containing cyclosporin or a macrolide |
| US7203158B2 (en) * | 2000-12-06 | 2007-04-10 | Matsushita Electric Industrial Co., Ltd. | OFDM signal transmission system, portable terminal, and e-commerce system |
| GB0526419D0 (en) * | 2005-12-23 | 2006-02-08 | Cyclacel Ltd | Formulation |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0711550A1 (en) * | 1994-11-09 | 1996-05-15 | Hanmi Pharm. Ind. Co., Ltd. | Cyclosporin-containing soft capsule compositions |
| GB2295546A (en) * | 1994-11-21 | 1996-06-05 | Biogal Gyogyszergyar | Composition comprising Cyclosporin and a Vitamin E derivative |
| US5589455A (en) * | 1994-12-28 | 1996-12-31 | Hanmi Pharm. Ind. Co., Ltd. | Cyclosporin-containing soft capsule compositions |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6465627B2 (en) * | 1995-07-28 | 2002-10-15 | The Regents Of The University Of California | DAX-1 protein, methods for production and use thereof |
| NZ280689A (en) * | 1995-12-15 | 1997-08-22 | Bernard Charles Sherma Sherman | Pharmaceutical composition comprising a cyclosporipharmaceutical composition comprising a cyclosporin; a tocol, tocopherol or tocotrienol; and propylen; a tocol, tocopherol or tocotrienol; and propylene carbonate or polyethylene glycol ne carbonate or polyethylene glycol |
| CZ292378B6 (cs) * | 1996-06-19 | 2003-09-17 | Novartis Ag | Přípravek obsahující cyklosporin a způsob jeho přípravy |
| KR0183449B1 (ko) * | 1996-06-19 | 1999-05-01 | 한스 루돌프 하우스, 니콜 케르커 | 사이클로스포린-함유 연질캅셀제 |
-
1997
- 1997-03-14 KR KR1019970008750A patent/KR19980073479A/ko not_active Ceased
-
1998
- 1998-03-12 CZ CZ993243A patent/CZ324399A3/cs unknown
- 1998-03-12 GB GB9921495A patent/GB2337703A/en not_active Withdrawn
- 1998-03-12 CA CA002283901A patent/CA2283901A1/en not_active Abandoned
- 1998-03-12 SK SK1232-99A patent/SK123299A3/sk unknown
- 1998-03-12 KR KR1019997008022A patent/KR20000075940A/ko not_active Ceased
- 1998-03-12 EP EP98912470A patent/EP0969857A1/en not_active Withdrawn
- 1998-03-12 RU RU99121398/14A patent/RU2185188C2/ru not_active IP Right Cessation
- 1998-03-12 WO PCT/EP1998/001432 patent/WO1998041225A1/en not_active Application Discontinuation
- 1998-03-12 BR BR9808324-4A patent/BR9808324A/pt not_active Application Discontinuation
- 1998-03-12 CN CNB988033569A patent/CN1161150C/zh not_active Expired - Fee Related
- 1998-03-12 PE PE1998000174A patent/PE59499A1/es not_active Application Discontinuation
- 1998-03-12 MY MYPI98001086A patent/MY118614A/en unknown
- 1998-03-12 HU HU0001515A patent/HUP0001515A3/hu unknown
- 1998-03-12 DE DE19882184T patent/DE19882184T1/de not_active Withdrawn
- 1998-03-12 ZA ZA982117A patent/ZA982117B/xx unknown
- 1998-03-12 ID IDW990997A patent/ID23531A/id unknown
- 1998-03-12 TR TR1999/02229T patent/TR199902229T2/xx unknown
- 1998-03-12 AU AU67293/98A patent/AU741923B2/en not_active Ceased
- 1998-03-12 JP JP54011298A patent/JP3748573B2/ja not_active Expired - Fee Related
- 1998-03-12 IL IL13170398A patent/IL131703A0/xx unknown
- 1998-03-12 PL PL98335729A patent/PL335729A1/xx unknown
- 1998-03-13 AR ARP980101125A patent/AR012054A1/es not_active Application Discontinuation
- 1998-03-13 CO CO98014254A patent/CO4940404A1/es unknown
-
1999
- 1999-09-13 NO NO994436A patent/NO994436L/no not_active Application Discontinuation
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0711550A1 (en) * | 1994-11-09 | 1996-05-15 | Hanmi Pharm. Ind. Co., Ltd. | Cyclosporin-containing soft capsule compositions |
| GB2295546A (en) * | 1994-11-21 | 1996-06-05 | Biogal Gyogyszergyar | Composition comprising Cyclosporin and a Vitamin E derivative |
| US5589455A (en) * | 1994-12-28 | 1996-12-31 | Hanmi Pharm. Ind. Co., Ltd. | Cyclosporin-containing soft capsule compositions |
Also Published As
| Publication number | Publication date |
|---|---|
| WO1998041225A1 (en) | 1998-09-24 |
| SK123299A3 (en) | 2000-02-14 |
| CN1250378A (zh) | 2000-04-12 |
| KR19980073479A (ko) | 1998-11-05 |
| JP3748573B2 (ja) | 2006-02-22 |
| AU6729398A (en) | 1998-10-12 |
| EP0969857A1 (en) | 2000-01-12 |
| NO994436D0 (no) | 1999-09-13 |
| NO994436L (no) | 1999-09-13 |
| TR199902229T2 (xx) | 1999-12-21 |
| CA2283901A1 (en) | 1998-09-24 |
| MY118614A (en) | 2004-12-31 |
| ZA982117B (en) | 1998-09-14 |
| GB9921495D0 (en) | 1999-11-17 |
| PE59499A1 (es) | 1999-07-05 |
| PL335729A1 (en) | 2000-05-08 |
| JP2000514831A (ja) | 2000-11-07 |
| KR20000075940A (ko) | 2000-12-26 |
| HUP0001515A3 (en) | 2000-10-30 |
| DE19882184T1 (de) | 2000-02-10 |
| CN1161150C (zh) | 2004-08-11 |
| CO4940404A1 (es) | 2000-07-24 |
| GB2337703A (en) | 1999-12-01 |
| AU741923B2 (en) | 2001-12-13 |
| IL131703A0 (en) | 2001-03-19 |
| CZ324399A3 (cs) | 1999-12-15 |
| ID23531A (id) | 2000-04-27 |
| AR012054A1 (es) | 2000-09-27 |
| HUP0001515A2 (hu) | 2000-09-28 |
| BR9808324A (pt) | 2000-05-16 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US5589455A (en) | Cyclosporin-containing soft capsule compositions | |
| RU2181055C2 (ru) | Препараты, содержащие циклоспорин, в виде капсул с мягким покрытием | |
| EP0813876B1 (en) | Cyclosporin-containing soft capsule preparations | |
| US5958876A (en) | Cyclosporin-containing pharmaceutical compositions | |
| RU2185188C2 (ru) | Фармацевтические композиции | |
| AU753018B2 (en) | Cyclosporin-containing soft capsule preparations | |
| AU722285B2 (en) | Cyclosporin-containing soft capsule preparations | |
| MXPA99008438A (en) | Pharmaceutical compositions | |
| HK1010492B (en) | Cyclosporin-containing soft capsule preparations | |
| HK1006780B (en) | Cyclosporin-containing soft capsule preparations | |
| AU1944200A (en) | Cyclosporin-containing soft capsule preparations |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MM4A | The patent is invalid due to non-payment of fees |
Effective date: 20060313 |