CA1329548C - Preparation de liposomes et antibiotique - Google Patents

Preparation de liposomes et antibiotique

Info

Publication number: CA1329548C
Authority: CA; Canada
Prior art keywords: liposomes; aminoglycoside; lipid; drug; gentamicin
Prior art date: 1985-06-26
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.): Expired - Fee Related

Application number

CA000616438A

Other languages

English (en)

Inventor

Marcel B. Bally

Lois E. Bolcsak

Pieter R. Cullis

Andrew S. Janoff

Lawrence D. Mayer

Robert P. Link

Jo Ann Jedrusiak

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.)

Elan Pharmaceuticals LLC

Original Assignee

Liposome Co Inc

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.)

1985-06-26

Filing date

1992-07-13

Publication date

1994-05-17

1987-01-13 Priority claimed from CA000527232A external-priority patent/CA1314481C/fr

1992-07-13 Application filed by Liposome Co Inc filed Critical Liposome Co Inc

1992-07-13 Priority to CA000616438A priority Critical patent/CA1329548C/fr

1994-05-17 Application granted granted Critical

1994-05-17 Publication of CA1329548C publication Critical patent/CA1329548C/fr

2007-01-13 Anticipated expiration legal-status Critical

Status Expired - Fee Related legal-status Critical Current

Links

238000002360 preparation method Methods 0.000 title description 27
230000003115 biocidal effect Effects 0.000 title description 3
229940126575 aminoglycoside Drugs 0.000 claims abstract description 128
239000002502 liposome Substances 0.000 claims abstract description 111
150000002632 lipids Chemical class 0.000 claims abstract description 73
238000000034 method Methods 0.000 claims abstract description 68
239000003814 drug Substances 0.000 claims abstract description 29
229940079593 drug Drugs 0.000 claims abstract description 28
239000008346 aqueous phase Substances 0.000 claims abstract description 22
239000002904 solvent Substances 0.000 claims abstract description 21
239000000463 material Substances 0.000 claims abstract description 15
239000003960 organic solvent Substances 0.000 claims abstract description 14
125000002795 guanidino group Chemical group C(N)(=N)N* 0.000 claims abstract description 10
241000145525 Spinach latent virus Species 0.000 claims abstract description 9
238000001704 evaporation Methods 0.000 claims abstract description 9
230000000087 stabilizing effect Effects 0.000 claims abstract description 7
239000012455 biphasic mixture Substances 0.000 claims abstract description 3
230000001804 emulsifying effect Effects 0.000 claims abstract description 3
229930182566 Gentamicin Natural products 0.000 claims description 25
CEAZRRDELHUEMR-URQXQFDESA-N Gentamicin Chemical compound O1[C@H](C(C)NC)CC[C@@H](N)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](NC)[C@@](C)(O)CO2)O)[C@H](N)C[C@@H]1N CEAZRRDELHUEMR-URQXQFDESA-N 0.000 claims description 25
229960002518 gentamicin Drugs 0.000 claims description 25
230000008569 process Effects 0.000 claims description 22
239000000203 mixture Substances 0.000 claims description 21
238000001035 drying Methods 0.000 claims description 9
DNYGXMICFMACRA-UHFFFAOYSA-N gentamicin C1A Natural products O1C(CNC)CCC(N)C1OC1C(O)C(OC2C(C(NC)C(C)(O)CO2)O)C(N)CC1N DNYGXMICFMACRA-UHFFFAOYSA-N 0.000 claims description 5
UOZODPSAJZTQNH-UHFFFAOYSA-N Paromomycin II Natural products NC1C(O)C(O)C(CN)OC1OC1C(O)C(OC2C(C(N)CC(N)C2O)OC2C(C(O)C(O)C(CO)O2)N)OC1CO UOZODPSAJZTQNH-UHFFFAOYSA-N 0.000 claims description 4
URWAJWIAIPFPJE-UHFFFAOYSA-N Rickamicin Natural products O1CC(O)(C)C(NC)C(O)C1OC1C(O)C(OC2C(CC=C(CN)O2)N)C(N)CC1N URWAJWIAIPFPJE-UHFFFAOYSA-N 0.000 claims description 4
229930192786 Sisomicin Natural products 0.000 claims description 4
229960001192 bekanamycin Drugs 0.000 claims description 4
VEGXETMJINRLTH-BOZYPMBZSA-N gentamycin C1a Chemical compound O1C[C@@](O)(C)[C@H](NC)[C@@H](O)[C@H]1O[C@@H]1[C@@H](O)[C@H](O[C@@H]2[C@@H](CC[C@@H](CN)O2)N)[C@@H](N)C[C@H]1N VEGXETMJINRLTH-BOZYPMBZSA-N 0.000 claims description 4
229960000318 kanamycin Drugs 0.000 claims description 4
SBUJHOSQTJFQJX-NOAMYHISSA-N kanamycin Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CN)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](N)[C@H](O)[C@@H](CO)O2)O)[C@H](N)C[C@@H]1N SBUJHOSQTJFQJX-NOAMYHISSA-N 0.000 claims description 4
229930182823 kanamycin A Natural products 0.000 claims description 4
229930182824 kanamycin B Natural products 0.000 claims description 4
SKKLOUVUUNMCJE-FQSMHNGLSA-N kanamycin B Chemical compound N[C@@H]1[C@@H](O)[C@H](O)[C@@H](CN)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](N)[C@H](O)[C@@H](CO)O2)O)[C@H](N)C[C@@H]1N SKKLOUVUUNMCJE-FQSMHNGLSA-N 0.000 claims description 4
229960001914 paromomycin Drugs 0.000 claims description 4
UOZODPSAJZTQNH-LSWIJEOBSA-N paromomycin Chemical compound N[C@@H]1[C@@H](O)[C@H](O)[C@H](CN)O[C@@H]1O[C@H]1[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](N)C[C@@H](N)[C@@H]2O)O[C@@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O2)N)O[C@@H]1CO UOZODPSAJZTQNH-LSWIJEOBSA-N 0.000 claims description 4
229960005456 sisomicin Drugs 0.000 claims description 4
URWAJWIAIPFPJE-YFMIWBNJSA-N sisomycin Chemical compound O1C[C@@](O)(C)[C@H](NC)[C@@H](O)[C@H]1O[C@@H]1[C@@H](O)[C@H](O[C@@H]2[C@@H](CC=C(CN)O2)N)[C@@H](N)C[C@H]1N URWAJWIAIPFPJE-YFMIWBNJSA-N 0.000 claims description 4
UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical group CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 claims description 4
229960000707 tobramycin Drugs 0.000 claims description 4
NLVFBUXFDBBNBW-PBSUHMDJSA-N tobramycin Chemical compound N[C@@H]1C[C@H](O)[C@@H](CN)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](N)[C@H](O)[C@@H](CO)O2)O)[C@H](N)C[C@@H]1N NLVFBUXFDBBNBW-PBSUHMDJSA-N 0.000 claims description 4
CEAZRRDELHUEMR-CAMVTXANSA-N (2r,3r,4r,5r)-2-[(1s,2s,3r,4s,6r)-4,6-diamino-3-[(2r,3r,6s)-3-amino-6-[(1r)-1-(methylamino)ethyl]oxan-2-yl]oxy-2-hydroxycyclohexyl]oxy-5-methyl-4-(methylamino)oxane-3,5-diol Chemical compound O1[C@H]([C@@H](C)NC)CC[C@@H](N)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](NC)[C@@](C)(O)CO2)O)[C@H](N)C[C@@H]1N CEAZRRDELHUEMR-CAMVTXANSA-N 0.000 claims description 3
229930183998 Lividomycin Natural products 0.000 claims description 3
229960004821 amikacin Drugs 0.000 claims description 3
LKCWBDHBTVXHDL-RMDFUYIESA-N amikacin Chemical compound O([C@@H]1[C@@H](N)C[C@H]([C@@H]([C@H]1O)O[C@@H]1[C@@H]([C@@H](N)[C@H](O)[C@@H](CO)O1)O)NC(=O)[C@@H](O)CCN)[C@H]1O[C@H](CN)[C@@H](O)[C@H](O)[C@H]1O LKCWBDHBTVXHDL-RMDFUYIESA-N 0.000 claims description 3
XUFIWSHGXVLULG-JYDJLPLMSA-N gentamycin C2 Chemical compound O1C[C@@](O)(C)[C@H](NC)[C@@H](O)[C@H]1O[C@H]1[C@@H](O)[C@H](O[C@@H]2[C@@H](CC[C@H](O2)[C@@H](C)N)N)[C@@H](N)C[C@H]1N XUFIWSHGXVLULG-JYDJLPLMSA-N 0.000 claims description 3
229950003076 lividomycin Drugs 0.000 claims description 3
DBLVDAUGBTYDFR-SWMBIRFSSA-N lividomycin A Chemical compound O([C@@H]1[C@@H](N)C[C@@H](N)[C@H](O)[C@H]1O[C@@H]1O[C@H](CO)[C@H]([C@H]1O)O[C@H]1O[C@H]([C@H]([C@H](O)[C@H]1N)O[C@@H]1[C@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)CN)[C@H]1O[C@H](CO)[C@@H](O)C[C@H]1N DBLVDAUGBTYDFR-SWMBIRFSSA-N 0.000 claims description 3
229960000808 netilmicin Drugs 0.000 claims description 3
ZBGPYVZLYBDXKO-HILBYHGXSA-N netilmycin Chemical compound O([C@@H]1[C@@H](N)C[C@H]([C@@H]([C@H]1O)O[C@@H]1[C@]([C@H](NC)[C@@H](O)CO1)(C)O)NCC)[C@H]1OC(CN)=CC[C@H]1N ZBGPYVZLYBDXKO-HILBYHGXSA-N 0.000 claims description 3
229960003485 ribostamycin Drugs 0.000 claims description 3
229930190553 ribostamycin Natural products 0.000 claims description 3
NSKGQURZWSPSBC-NLZFXWNVSA-N ribostamycin Chemical compound N[C@H]1[C@H](O)[C@@H](O)[C@H](CN)O[C@@H]1O[C@@H]1[C@@H](O[C@H]2[C@@H]([C@@H](O)[C@H](CO)O2)O)[C@H](O)[C@@H](N)C[C@H]1N NSKGQURZWSPSBC-NLZFXWNVSA-N 0.000 claims description 3
NSKGQURZWSPSBC-UHFFFAOYSA-N ribostamycin A Natural products NC1C(O)C(O)C(CN)OC1OC1C(OC2C(C(O)C(CO)O2)O)C(O)C(N)CC1N NSKGQURZWSPSBC-UHFFFAOYSA-N 0.000 claims description 3
150000003467 sulfuric acid derivatives Chemical class 0.000 claims description 3
201000001178 Bacterial Pneumonia Diseases 0.000 claims description 2
229960003704 framycetin Drugs 0.000 claims description 2
PGBHMTALBVVCIT-VCIWKGPPSA-N framycetin Chemical group N[C@@H]1[C@@H](O)[C@H](O)[C@H](CN)O[C@@H]1O[C@H]1[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](N)C[C@@H](N)[C@@H]2O)O[C@@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CN)O2)N)O[C@@H]1CO PGBHMTALBVVCIT-VCIWKGPPSA-N 0.000 claims description 2
229930076781 gentamycin C1 Natural products 0.000 claims description 2
229960005322 streptomycin Drugs 0.000 claims description 2
208000035473 Communicable disease Diseases 0.000 claims 2
208000015181 infectious disease Diseases 0.000 claims 2
239000008194 pharmaceutical composition Substances 0.000 claims 1
229910019142 PO4 Inorganic materials 0.000 description 56
235000021317 phosphate Nutrition 0.000 description 56
239000010452 phosphate Substances 0.000 description 52
NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 51
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 13
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 12
150000003013 phosphoric acid derivatives Chemical class 0.000 description 12
239000000843 powder Substances 0.000 description 12
239000002585 base Substances 0.000 description 11
229910001868 water Inorganic materials 0.000 description 11
150000003839 salts Chemical class 0.000 description 9
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
150000001875 compounds Chemical class 0.000 description 8
RDEIXVOBVLKYNT-VQBXQJRRSA-N (2r,3r,4r,5r)-2-[(1s,2s,3r,4s,6r)-4,6-diamino-3-[(2r,3r,6s)-3-amino-6-(1-aminoethyl)oxan-2-yl]oxy-2-hydroxycyclohexyl]oxy-5-methyl-4-(methylamino)oxane-3,5-diol;(2r,3r,4r,5r)-2-[(1s,2s,3r,4s,6r)-4,6-diamino-3-[(2r,3r,6s)-3-amino-6-(aminomethyl)oxan-2-yl]o Chemical compound OS(O)(=O)=O.O1C[C@@](O)(C)[C@H](NC)[C@@H](O)[C@H]1O[C@@H]1[C@@H](O)[C@H](O[C@@H]2[C@@H](CC[C@@H](CN)O2)N)[C@@H](N)C[C@H]1N.O1C[C@@](O)(C)[C@H](NC)[C@@H](O)[C@H]1O[C@@H]1[C@@H](O)[C@H](O[C@@H]2[C@@H](CC[C@H](O2)C(C)N)N)[C@@H](N)C[C@H]1N.O1[C@H](C(C)NC)CC[C@@H](N)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](NC)[C@@](C)(O)CO2)O)[C@H](N)C[C@@H]1N RDEIXVOBVLKYNT-VQBXQJRRSA-N 0.000 description 7
230000002209 hydrophobic effect Effects 0.000 description 7
239000012071 phase Substances 0.000 description 7
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
239000012528 membrane Substances 0.000 description 6
229910052757 nitrogen Inorganic materials 0.000 description 6
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 5
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 5
239000000872 buffer Substances 0.000 description 5
238000001125 extrusion Methods 0.000 description 5
230000008014 freezing Effects 0.000 description 5
238000007710 freezing Methods 0.000 description 5
239000007788 liquid Substances 0.000 description 5
150000003904 phospholipids Chemical class 0.000 description 5
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
241001465754 Metazoa Species 0.000 description 4
230000008020 evaporation Effects 0.000 description 4
239000010408 film Substances 0.000 description 4
239000000499 gel Substances 0.000 description 4
150000002337 glycosamines Chemical class 0.000 description 4
150000002500 ions Chemical class 0.000 description 4
-1 phosphate salt Chemical class 0.000 description 4
230000036515 potency Effects 0.000 description 4
230000002829 reductive effect Effects 0.000 description 4
239000000243 solution Substances 0.000 description 4
235000000346 sugar Nutrition 0.000 description 4
230000001988 toxicity Effects 0.000 description 4
231100000419 toxicity Toxicity 0.000 description 4
230000007704 transition Effects 0.000 description 4
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
238000012424 Freeze-thaw process Methods 0.000 description 3
QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 3
230000002411 adverse Effects 0.000 description 3
238000000502 dialysis Methods 0.000 description 3
239000006185 dispersion Substances 0.000 description 3
229930195733 hydrocarbon Natural products 0.000 description 3
150000002430 hydrocarbons Chemical class 0.000 description 3
238000001990 intravenous administration Methods 0.000 description 3
125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 description 3
239000002243 precursor Substances 0.000 description 3
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 3
230000001681 protective effect Effects 0.000 description 3
239000011780 sodium chloride Substances 0.000 description 3
CMXPERZAMAQXSF-UHFFFAOYSA-M sodium;1,4-bis(2-ethylhexoxy)-1,4-dioxobutane-2-sulfonate;1,8-dihydroxyanthracene-9,10-dione Chemical compound [Na+].O=C1C2=CC=CC(O)=C2C(=O)C2=C1C=CC=C2O.CCCCC(CC)COC(=O)CC(S([O-])(=O)=O)C(=O)OCC(CC)CCCC CMXPERZAMAQXSF-UHFFFAOYSA-M 0.000 description 3
150000008163 sugars Chemical class 0.000 description 3
230000001225 therapeutic effect Effects 0.000 description 3
230000000699 topical effect Effects 0.000 description 3
239000002691 unilamellar liposome Substances 0.000 description 3
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 3
WEEMDRWIKYCTQM-UHFFFAOYSA-N 2,6-dimethoxybenzenecarbothioamide Chemical compound COC1=CC=CC(OC)=C1C(N)=S WEEMDRWIKYCTQM-UHFFFAOYSA-N 0.000 description 2
AWBXTNNIECFIHT-XZQQZIICSA-N 2-[(1r,2r,3s,4r,5r,6s)-3-(diaminomethylideneamino)-4-[(2r,3r,4r,5s)-3-[(2s,3s,4s,5r,6s)-4,5-dihydroxy-6-(hydroxymethyl)-3-(methylamino)oxan-2-yl]oxy-4-formyl-4-hydroxy-5-methyloxolan-2-yl]oxy-2,5,6-trihydroxycyclohexyl]guanidine;2-[(1r,2r,3s,4r,5r,6s)-3-( Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](CO)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](N=C(N)N)[C@H](O)[C@@H](N=C(N)N)[C@H](O)[C@H]1O.CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](N=C(N)N)[C@H](O)[C@@H](N=C(N)N)[C@H](O)[C@H]1O AWBXTNNIECFIHT-XZQQZIICSA-N 0.000 description 2
JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 2
RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 2
241000894006 Bacteria Species 0.000 description 2
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 2
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241000714177 Murine leukemia virus Species 0.000 description 2
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240000000220 Panda oleosa Species 0.000 description 2
235000016496 Panda oleosa Nutrition 0.000 description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
241000534944 Thia Species 0.000 description 2
XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
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LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 2
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238000007918 intramuscular administration Methods 0.000 description 2
229930190071 lycoside Natural products 0.000 description 2
238000004519 manufacturing process Methods 0.000 description 2
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
229960004927 neomycin Drugs 0.000 description 2
239000002953 phosphate buffered saline Substances 0.000 description 2
WTJKGGKOPKCXLL-RRHRGVEJSA-N phosphatidylcholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCC=CCCCCCCCC WTJKGGKOPKCXLL-RRHRGVEJSA-N 0.000 description 2
230000036470 plasma concentration Effects 0.000 description 2
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239000004417 polycarbonate Substances 0.000 description 2
230000003389 potentiating effect Effects 0.000 description 2
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241000894007 species Species 0.000 description 2
229960002385 streptomycin sulfate Drugs 0.000 description 2
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239000000725 suspension Substances 0.000 description 2
238000004448 titration Methods 0.000 description 2
229930003799 tocopherol Natural products 0.000 description 2
239000011732 tocopherol Substances 0.000 description 2
230000014616 translation Effects 0.000 description 2
150000003626 triacylglycerols Chemical class 0.000 description 2
VMPHSYLJUKZBJJ-UHFFFAOYSA-N trilaurin Chemical compound CCCCCCCCCCCC(=O)OCC(OC(=O)CCCCCCCCCCC)COC(=O)CCCCCCCCCCC VMPHSYLJUKZBJJ-UHFFFAOYSA-N 0.000 description 2
DUXYWXYOBMKGIN-UHFFFAOYSA-N trimyristin Chemical compound CCCCCCCCCCCCCC(=O)OCC(OC(=O)CCCCCCCCCCCCC)COC(=O)CCCCCCCCCCCCC DUXYWXYOBMKGIN-UHFFFAOYSA-N 0.000 description 2
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CA000616438A 1985-06-26 1992-07-13 Preparation de liposomes et antibiotique Expired - Fee Related CA1329548C (fr)

Priority Applications (1)

Application Number	Priority Date	Filing Date	Title
CA000616438A CA1329548C (fr)	1985-06-26	1992-07-13	Preparation de liposomes et antibiotique

Applications Claiming Priority (12)

Application Number	Priority Date	Filing Date	Title
US74916185A	1985-06-26	1985-06-26
US749,161		1985-06-26
US75242385A	1985-07-05	1985-07-05
US752,423		1985-07-05
US80054585A	1985-11-21	1985-11-21
US800,545		1985-11-21
US94639186A	1986-12-23	1986-12-23
US94639886A	1986-12-23	1986-12-23
US946,398		1986-12-23
US946,391		1986-12-23
CA000527232A CA1314481C (fr)	1986-12-23	1987-01-13	Preparation a base de lipodomes et antibiotique
CA000616438A CA1329548C (fr)	1985-06-26	1992-07-13	Preparation de liposomes et antibiotique

Related Parent Applications (1)

Application Number	Title	Priority Date	Filing Date
CA000527232A Division CA1314481C (fr)	1985-06-26	1987-01-13	Preparation a base de lipodomes et antibiotique

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CA1329548C true CA1329548C (fr)	1994-05-17

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CA000616438A Expired - Fee Related CA1329548C (fr)	1985-06-26	1992-07-13	Preparation de liposomes et antibiotique

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1992
- 1992-07-13 CA CA000616438A patent/CA1329548C/fr not_active Expired - Fee Related

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Date	Code	Title	Description
2006-05-17	MKLA	Lapsed
2023-05-26	MKLA	Lapsed	Effective date: 20060517

Publication	Publication Date	Title
EP0498471B1 (fr)	1996-08-14	Liposomes contenant un guanidino-aminoglycoside
US5409704A (en)	1995-04-25	Liposomes comprising aminoglycoside phosphates and methods of production and use
EP0191824B1 (fr)	1993-10-27	Encapsulement d'agents antineoplastiques dans des liposomes
US5874104A (en)	1999-02-23	Treatment of systemic fungal infections with phospholipid particles encapsulating polyene antibiotics
US6406713B1 (en)	2002-06-18	Methods of preparing low-toxicity drug-lipid complexes
US5077056A (en)	1991-12-31	Encapsulation of antineoplastic agents in liposomes
US5616334A (en)	1997-04-01	Low toxicity drug-lipid systems
US5736155A (en)	1998-04-07	Encapsulation of antineoplastic agents in liposomes
HK1007494B (en)	1999-04-16	Encapsulation of antineoplastic agents in liposomes
CA1308025C (fr)	1992-09-29	Composition de phospholipide
EP0282405B2 (fr)	1998-07-22	Systèmes médicament-lipide à basse toxicité
AU2788689A (en)	1989-05-02	Polyene macrolide pre-liposomal powders
CA1329548C (fr)	1994-05-17	Preparation de liposomes et antibiotique
EP0393145A1 (fr)	1990-10-24	Vesiculation spontanee de liposomes multilamellaires
US5043107A (en)	1991-08-27	Preparation small unilamellar vesicles including polyene antifungal antibiotics
AU641532B2 (en)	1993-09-23	Liposome preparation and antibiotic
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