CA1340519C - Nucleosides antiviraux - Google Patents

Nucleosides antiviraux

Info

Publication number: CA1340519C
Authority: CA; Canada
Prior art keywords: deoxythymidine; azido; treatment; prophylaxis; human
Prior art date: 1985-03-16
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

CA000616284A

Other languages

English (en)

Inventor

David Walter Barry

Sandra Nusinoff Lehrman

Phillip Allen Furman

Martha Heider St Clair

Janet Litster Rideout

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.)

Wellcome Foundation Ltd

Original Assignee

Wellcome Foundation Ltd

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.)

1985-03-16

Filing date

1992-01-13

Publication date

1999-04-27

1985-03-16 Priority claimed from GB858506869A external-priority patent/GB8506869D0/en

1985-05-09 Priority claimed from GB858511774A external-priority patent/GB8511774D0/en

1985-09-17 Priority claimed from US06/776,899 external-priority patent/US4724232A/en

1985-09-27 Priority claimed from GB858523881A external-priority patent/GB8523881D0/en

1986-02-12 Priority claimed from GB868603450A external-priority patent/GB8603450D0/en

1988-01-20 Priority claimed from CA000556981A external-priority patent/CA1303032C/fr

1992-01-13 Application filed by Wellcome Foundation Ltd filed Critical Wellcome Foundation Ltd

1992-01-13 Priority to CA000616284A priority Critical patent/CA1340519C/fr

1999-04-27 Application granted granted Critical

1999-04-27 Publication of CA1340519C publication Critical patent/CA1340519C/fr

2006-03-14 Anticipated expiration legal-status Critical

Status Expired - Fee Related legal-status Critical Current

Links

230000000840 anti-viral effect Effects 0.000 title description 4
239000002777 nucleoside Substances 0.000 title 1
125000003835 nucleoside group Chemical group 0.000 title 1
HBOMLICNUCNMMY-XLPZGREQSA-N zidovudine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](N=[N+]=[N-])C1 HBOMLICNUCNMMY-XLPZGREQSA-N 0.000 claims abstract description 68
238000011282 treatment Methods 0.000 claims abstract description 41
238000011321 prophylaxis Methods 0.000 claims abstract description 31
239000000203 mixture Substances 0.000 claims description 53
241000282414 Homo sapiens Species 0.000 claims description 40
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 claims description 26
208000015181 infectious disease Diseases 0.000 claims description 24
239000003814 drug Substances 0.000 claims description 19
208000030507 AIDS Diseases 0.000 claims description 18
239000002552 dosage form Substances 0.000 claims description 13
206010020460 Human T-cell lymphotropic virus type I infection Diseases 0.000 claims description 12
241000714260 Human T-lymphotropic virus 1 Species 0.000 claims description 10
238000004519 manufacturing process Methods 0.000 claims description 10
239000008194 pharmaceutical composition Substances 0.000 claims description 10
206010001513 AIDS related complex Diseases 0.000 claims description 8
210000001744 T-lymphocyte Anatomy 0.000 claims description 8
230000009385 viral infection Effects 0.000 claims description 7
208000005074 Retroviridae Infections Diseases 0.000 claims description 6
208000031886 HIV Infections Diseases 0.000 claims description 5
208000037357 HIV infectious disease Diseases 0.000 claims description 5
208000033519 human immunodeficiency virus infectious disease Diseases 0.000 claims description 5
230000036436 anti-hiv Effects 0.000 claims description 3
230000000798 anti-retroviral effect Effects 0.000 claims description 2
239000003937 drug carrier Substances 0.000 claims 9
208000005599 HTLV-I Infections Diseases 0.000 claims 5
208000007687 HTLV-II Infections Diseases 0.000 claims 5
208000031957 HIV carrier Diseases 0.000 claims 2
241001430294 unidentified retrovirus Species 0.000 abstract description 13
239000004480 active ingredient Substances 0.000 description 41
210000004027 cell Anatomy 0.000 description 36
238000009472 formulation Methods 0.000 description 34
241000725303 Human immunodeficiency virus Species 0.000 description 27
230000000694 effects Effects 0.000 description 21
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 16
150000001875 compounds Chemical class 0.000 description 15
241000700605 Viruses Species 0.000 description 13
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 13
239000000243 solution Substances 0.000 description 12
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 11
239000003826 tablet Substances 0.000 description 11
239000004615 ingredient Substances 0.000 description 10
102000004190 Enzymes Human genes 0.000 description 8
108090000790 Enzymes Proteins 0.000 description 8
102100034343 Integrase Human genes 0.000 description 8
WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 8
108010092799 RNA-directed DNA polymerase Proteins 0.000 description 8
239000002775 capsule Substances 0.000 description 8
229940079593 drug Drugs 0.000 description 8
235000019359 magnesium stearate Nutrition 0.000 description 8
235000013855 polyvinylpyrrolidone Nutrition 0.000 description 8
229920000036 polyvinylpyrrolidone Polymers 0.000 description 8
229940069328 povidone Drugs 0.000 description 8
108020004414 DNA Proteins 0.000 description 7
GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 7
206010028980 Neoplasm Diseases 0.000 description 7
239000008101 lactose Substances 0.000 description 7
239000007788 liquid Substances 0.000 description 7
238000000034 method Methods 0.000 description 7
WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 6
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
208000032839 leukemia Diseases 0.000 description 6
241001529936 Murinae Species 0.000 description 5
239000000969 carrier Substances 0.000 description 5
238000002474 experimental method Methods 0.000 description 5
210000002845 virion Anatomy 0.000 description 5
LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 4
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
210000004369 blood Anatomy 0.000 description 4
239000008280 blood Substances 0.000 description 4
238000013270 controlled release Methods 0.000 description 4
230000000120 cytopathologic effect Effects 0.000 description 4
235000011187 glycerol Nutrition 0.000 description 4
238000000338 in vitro Methods 0.000 description 4
239000000843 powder Substances 0.000 description 4
229940080313 sodium starch Drugs 0.000 description 4
239000000829 suppository Substances 0.000 description 4
239000000725 suspension Substances 0.000 description 4
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
206010038997 Retroviral infections Diseases 0.000 description 3
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
230000037396 body weight Effects 0.000 description 3
239000003795 chemical substances by application Substances 0.000 description 3
238000007906 compression Methods 0.000 description 3
230000006835 compression Effects 0.000 description 3
NHVNXKFIZYSCEB-XLPZGREQSA-N dTTP Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)[C@@H](O)C1 NHVNXKFIZYSCEB-XLPZGREQSA-N 0.000 description 3
238000007907 direct compression Methods 0.000 description 3
238000011049 filling Methods 0.000 description 3
239000000796 flavoring agent Substances 0.000 description 3
239000007903 gelatin capsule Substances 0.000 description 3
239000008187 granular material Substances 0.000 description 3
229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 3
238000007918 intramuscular administration Methods 0.000 description 3
239000002245 particle Substances 0.000 description 3
ZJAOAACCNHFJAH-UHFFFAOYSA-N phosphonoformic acid Chemical compound OC(=O)P(O)(O)=O ZJAOAACCNHFJAH-UHFFFAOYSA-N 0.000 description 3
208000024891 symptom Diseases 0.000 description 3
238000002560 therapeutic procedure Methods 0.000 description 3
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 2
CTPDSKVQLSDPLC-UHFFFAOYSA-N 2-(oxolan-2-ylmethoxy)ethanol Chemical compound OCCOCC1CCCO1 CTPDSKVQLSDPLC-UHFFFAOYSA-N 0.000 description 2
235000003911 Arachis Nutrition 0.000 description 2
244000105624 Arachis hypogaea Species 0.000 description 2
241000713838 Avian myeloblastosis virus Species 0.000 description 2
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 2
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 2
108010010803 Gelatin Proteins 0.000 description 2
108010078851 HIV Reverse Transcriptase Proteins 0.000 description 2
241000598436 Human T-cell lymphotropic virus Species 0.000 description 2
241000714259 Human T-lymphotropic virus 2 Species 0.000 description 2
241000701085 Human alphaherpesvirus 3 Species 0.000 description 2
235000010643 Leucaena leucocephala Nutrition 0.000 description 2
240000007472 Leucaena leucocephala Species 0.000 description 2
TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
229910021380 Manganese Chloride Inorganic materials 0.000 description 2
GLFNIEUTAYBVOC-UHFFFAOYSA-L Manganese chloride Chemical compound Cl[Mn]Cl GLFNIEUTAYBVOC-UHFFFAOYSA-L 0.000 description 2
208000001388 Opportunistic Infections Diseases 0.000 description 2
PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
206010041660 Splenomegaly Diseases 0.000 description 2
229930006000 Sucrose Natural products 0.000 description 2
CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
206010043376 Tetanus Diseases 0.000 description 2
MKUXAQIIEYXACX-UHFFFAOYSA-N aciclovir Chemical compound N1C(N)=NC(=O)C2=C1N(COCCO)C=N2 MKUXAQIIEYXACX-UHFFFAOYSA-N 0.000 description 2
239000007864 aqueous solution Substances 0.000 description 2
235000019445 benzyl alcohol Nutrition 0.000 description 2
IQFYYKKMVGJFEH-UHFFFAOYSA-N beta-L-thymidine Natural products O=C1NC(=O)C(C)=CN1C1OC(CO)C(O)C1 IQFYYKKMVGJFEH-UHFFFAOYSA-N 0.000 description 2
230000015572 biosynthetic process Effects 0.000 description 2
239000007963 capsule composition Substances 0.000 description 2
210000003169 central nervous system Anatomy 0.000 description 2
230000034994 death Effects 0.000 description 2
231100000517 death Toxicity 0.000 description 2
230000003247 decreasing effect Effects 0.000 description 2
239000006185 dispersion Substances 0.000 description 2
239000000839 emulsion Substances 0.000 description 2
235000019634 flavors Nutrition 0.000 description 2
239000012634 fragment Substances 0.000 description 2
239000008273 gelatin Substances 0.000 description 2
229920000159 gelatin Polymers 0.000 description 2
235000019322 gelatine Nutrition 0.000 description 2
235000011852 gelatine desserts Nutrition 0.000 description 2
239000011521 glass Substances 0.000 description 2
238000009396 hybridization Methods 0.000 description 2
235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 2
239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 2
UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 2
238000000099 in vitro assay Methods 0.000 description 2
238000001802 infusion Methods 0.000 description 2
238000002347 injection Methods 0.000 description 2
239000007924 injection Substances 0.000 description 2
229940079322 interferon Drugs 0.000 description 2
238000001990 intravenous administration Methods 0.000 description 2
235000010445 lecithin Nutrition 0.000 description 2
239000000787 lecithin Substances 0.000 description 2
229940067606 lecithin Drugs 0.000 description 2
210000000265 leukocyte Anatomy 0.000 description 2
229960003511 macrogol Drugs 0.000 description 2
239000011565 manganese chloride Substances 0.000 description 2
235000002867 manganese chloride Nutrition 0.000 description 2
239000003550 marker Substances 0.000 description 2
239000000155 melt Substances 0.000 description 2
238000000465 moulding Methods 0.000 description 2
239000006072 paste Substances 0.000 description 2
201000003450 persistent generalized lymphadenopathy Diseases 0.000 description 2
239000000047 product Substances 0.000 description 2
230000000750 progressive effect Effects 0.000 description 2
239000008213 purified water Substances 0.000 description 2
230000010076 replication Effects 0.000 description 2
-1 s Species 0.000 description 2
239000000523 sample Substances 0.000 description 2
WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 2
235000010234 sodium benzoate Nutrition 0.000 description 2
239000004299 sodium benzoate Substances 0.000 description 2
239000011780 sodium chloride Substances 0.000 description 2
239000007787 solid Substances 0.000 description 2
239000000600 sorbitol Substances 0.000 description 2
241000894007 species Species 0.000 description 2
238000003756 stirring Methods 0.000 description 2
238000007920 subcutaneous administration Methods 0.000 description 2
239000005720 sucrose Substances 0.000 description 2
230000004083 survival effect Effects 0.000 description 2
239000007916 tablet composition Substances 0.000 description 2
238000012360 testing method Methods 0.000 description 2
239000002562 thickening agent Substances 0.000 description 2
229940104230 thymidine Drugs 0.000 description 2
210000001519 tissue Anatomy 0.000 description 2
230000000699 topical effect Effects 0.000 description 2
238000013518 transcription Methods 0.000 description 2
230000035897 transcription Effects 0.000 description 2
235000011178 triphosphate Nutrition 0.000 description 2
239000001226 triphosphate Substances 0.000 description 2
UNXRWKVEANCORM-UHFFFAOYSA-N triphosphoric acid Chemical compound OP(O)(=O)OP(O)(=O)OP(O)(O)=O UNXRWKVEANCORM-UHFFFAOYSA-N 0.000 description 2
230000003612 virological effect Effects 0.000 description 2
239000008215 water for injection Substances 0.000 description 2
238000005550 wet granulation Methods 0.000 description 2
OYEWYBHHEPLOBZ-CVJICSNFSA-N (2S,4S,5S)-4-azido-5-(hydroxymethyl)-2-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolane-2-carboxylic acid Chemical compound CC1=CN(C(=O)NC1=O)[C@]2(C[C@@H]([C@H](O2)CO)N=[N+]=[N-])C(=O)O OYEWYBHHEPLOBZ-CVJICSNFSA-N 0.000 description 1
HBOMLICNUCNMMY-UHFFFAOYSA-N 1-[4-azido-5-(hydroxymethyl)oxolan-2-yl]-5-methylpyrimidine-2,4-dione Chemical compound O=C1NC(=O)C(C)=CN1C1OC(CO)C(N=[N+]=[N-])C1 HBOMLICNUCNMMY-UHFFFAOYSA-N 0.000 description 1
OKQHSIGMOWQUIK-UHFFFAOYSA-N 2-[(2-aminopurin-9-yl)methoxy]ethanol Chemical compound NC1=NC=C2N=CN(COCCO)C2=N1 OKQHSIGMOWQUIK-UHFFFAOYSA-N 0.000 description 1
BDZHKUAKSMWSAJ-UHFFFAOYSA-N 2-chloro-n,n-diethyl-1,1,2-trifluoroethanamine Chemical compound CCN(CC)C(F)(F)C(F)Cl BDZHKUAKSMWSAJ-UHFFFAOYSA-N 0.000 description 1
YLDCUKJMEKGGFI-QCSRICIXSA-N 4-acetamidobenzoic acid;9-[(2r,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-3h-purin-6-one;1-(dimethylamino)propan-2-ol Chemical compound CC(O)CN(C)C.CC(O)CN(C)C.CC(O)CN(C)C.CC(=O)NC1=CC=C(C(O)=O)C=C1.CC(=O)NC1=CC=C(C(O)=O)C=C1.CC(=O)NC1=CC=C(C(O)=O)C=C1.O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(NC=NC2=O)=C2N=C1 YLDCUKJMEKGGFI-QCSRICIXSA-N 0.000 description 1
WOVKYSAHUYNSMH-RRKCRQDMSA-N 5-bromodeoxyuridine Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(Br)=C1 WOVKYSAHUYNSMH-RRKCRQDMSA-N 0.000 description 1
244000144730 Amygdalus persica Species 0.000 description 1
241000416162 Astragalus gummifer Species 0.000 description 1
206010003591 Ataxia Diseases 0.000 description 1
238000011725 BALB/c mouse Methods 0.000 description 1
WOVKYSAHUYNSMH-UHFFFAOYSA-N BROMODEOXYURIDINE Natural products C1C(O)C(CO)OC1N1C(=O)NC(=O)C(Br)=C1 WOVKYSAHUYNSMH-UHFFFAOYSA-N 0.000 description 1
108091003079 Bovine Serum Albumin Proteins 0.000 description 1
208000014644 Brain disease Diseases 0.000 description 1
208000014912 Central Nervous System Infections Diseases 0.000 description 1
229920002785 Croscarmellose sodium Polymers 0.000 description 1
241000450599 DNA viruses Species 0.000 description 1
108010014303 DNA-directed DNA polymerase Proteins 0.000 description 1
102000016928 DNA-directed DNA polymerase Human genes 0.000 description 1
102000004163 DNA-directed RNA polymerases Human genes 0.000 description 1
108090000626 DNA-directed RNA polymerases Proteins 0.000 description 1
208000016192 Demyelinating disease Diseases 0.000 description 1
206010012305 Demyelination Diseases 0.000 description 1
206010013887 Dysarthria Diseases 0.000 description 1
208000032274 Encephalopathy Diseases 0.000 description 1
239000001856 Ethyl cellulose Substances 0.000 description 1
ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 1
102000004678 Exoribonucleases Human genes 0.000 description 1
108010002700 Exoribonucleases Proteins 0.000 description 1
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 1
UYTPUPDQBNUYGX-UHFFFAOYSA-N Guanine Natural products O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 description 1
241000282412 Homo Species 0.000 description 1
238000012404 In vitro experiment Methods 0.000 description 1
102000014150 Interferons Human genes 0.000 description 1
108010050904 Interferons Proteins 0.000 description 1
102000000588 Interleukin-2 Human genes 0.000 description 1
108010002350 Interleukin-2 Proteins 0.000 description 1
HLFSDGLLUJUHTE-SNVBAGLBSA-N Levamisole Chemical compound C1([C@H]2CN3CCSC3=N2)=CC=CC=C1 HLFSDGLLUJUHTE-SNVBAGLBSA-N 0.000 description 1
206010025323 Lymphomas Diseases 0.000 description 1
229920003091 Methocel™ Polymers 0.000 description 1
229920000168 Microcrystalline cellulose Polymers 0.000 description 1
229920000881 Modified starch Polymers 0.000 description 1
241000713869 Moloney murine leukemia virus Species 0.000 description 1
241000699670 Mus sp. Species 0.000 description 1
239000007832 Na2SO4 Substances 0.000 description 1
206010035664 Pneumonia Diseases 0.000 description 1
235000006040 Prunus persica var persica Nutrition 0.000 description 1
241000700159 Rattus Species 0.000 description 1
IWUCXVSUMQZMFG-AFCXAGJDSA-N Ribavirin Chemical compound N1=C(C(=O)N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 IWUCXVSUMQZMFG-AFCXAGJDSA-N 0.000 description 1
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
108091008874 T cell receptors Proteins 0.000 description 1
102000016266 T-Cell Antigen Receptors Human genes 0.000 description 1
108010046075 Thymosin Proteins 0.000 description 1
102000007501 Thymosin Human genes 0.000 description 1
229920001615 Tragacanth Polymers 0.000 description 1
206010058874 Viraemia Diseases 0.000 description 1
108020005202 Viral DNA Proteins 0.000 description 1
238000010521 absorption reaction Methods 0.000 description 1
231100000230 acceptable toxicity Toxicity 0.000 description 1
229960004150 aciclovir Drugs 0.000 description 1
230000009471 action Effects 0.000 description 1
239000003963 antioxidant agent Substances 0.000 description 1
235000006708 antioxidants Nutrition 0.000 description 1
210000003719 b-lymphocyte Anatomy 0.000 description 1
230000004888 barrier function Effects 0.000 description 1
230000008901 benefit Effects 0.000 description 1
239000011230 binding agent Substances 0.000 description 1
230000036765 blood level Effects 0.000 description 1
210000001185 bone marrow Anatomy 0.000 description 1
229940098773 bovine serum albumin Drugs 0.000 description 1
210000004556 brain Anatomy 0.000 description 1
229950004398 broxuridine Drugs 0.000 description 1
239000000872 buffer Substances 0.000 description 1
201000011510 cancer Diseases 0.000 description 1
230000001413 cellular effect Effects 0.000 description 1
230000007541 cellular toxicity Effects 0.000 description 1
230000001684 chronic effect Effects 0.000 description 1
229940110456 cocoa butter Drugs 0.000 description 1
235000019868 cocoa butter Nutrition 0.000 description 1
230000002860 competitive effect Effects 0.000 description 1
230000006957 competitive inhibition Effects 0.000 description 1
239000007891 compressed tablet Substances 0.000 description 1
208000004209 confusion Diseases 0.000 description 1
239000006071 cream Substances 0.000 description 1
235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 description 1
239000001767 crosslinked sodium carboxy methyl cellulose Substances 0.000 description 1
235000013365 dairy product Nutrition 0.000 description 1
238000011161 development Methods 0.000 description 1
239000008121 dextrose Substances 0.000 description 1
239000003085 diluting agent Substances 0.000 description 1
239000001177 diphosphate Substances 0.000 description 1
XPPKVPWEQAFLFU-UHFFFAOYSA-J diphosphate(4-) Chemical compound [O-]P([O-])(=O)OP([O-])([O-])=O XPPKVPWEQAFLFU-UHFFFAOYSA-J 0.000 description 1
235000011180 diphosphates Nutrition 0.000 description 1
201000010099 disease Diseases 0.000 description 1
231100000676 disease causative agent Toxicity 0.000 description 1
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
239000007884 disintegrant Substances 0.000 description 1
206010013395 disorientation Diseases 0.000 description 1
239000002270 dispersing agent Substances 0.000 description 1
239000003651 drinking water Substances 0.000 description 1
235000020188 drinking water Nutrition 0.000 description 1
230000000857 drug effect Effects 0.000 description 1
238000001035 drying Methods 0.000 description 1
241001493065 dsRNA viruses Species 0.000 description 1
239000007904 elastic gelatin capsule Substances 0.000 description 1
238000010828 elution Methods 0.000 description 1
230000008029 eradication Effects 0.000 description 1
125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
235000019325 ethyl cellulose Nutrition 0.000 description 1
229920001249 ethyl cellulose Polymers 0.000 description 1
239000000284 extract Substances 0.000 description 1
238000001914 filtration Methods 0.000 description 1
239000006260 foam Substances 0.000 description 1
235000013355 food flavoring agent Nutrition 0.000 description 1
235000003599 food sweetener Nutrition 0.000 description 1
229960005102 foscarnet Drugs 0.000 description 1
239000000499 gel Substances 0.000 description 1
IVSXFFJGASXYCL-UHFFFAOYSA-N guanine Chemical compound O=C1NC(N)=NC2=NC=N[C]21 IVSXFFJGASXYCL-UHFFFAOYSA-N 0.000 description 1
229940116364 hard fat Drugs 0.000 description 1
WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
230000002519 immonomodulatory effect Effects 0.000 description 1
210000000987 immune system Anatomy 0.000 description 1
238000010348 incorporation Methods 0.000 description 1
230000006698 induction Effects 0.000 description 1
239000003701 inert diluent Substances 0.000 description 1
239000003112 inhibitor Substances 0.000 description 1
230000005764 inhibitory process Effects 0.000 description 1
230000000266 injurious effect Effects 0.000 description 1
238000010253 intravenous injection Methods 0.000 description 1
229960001614 levamisole Drugs 0.000 description 1
239000007937 lozenge Substances 0.000 description 1
239000000314 lubricant Substances 0.000 description 1
210000004698 lymphocyte Anatomy 0.000 description 1
210000002540 macrophage Anatomy 0.000 description 1
229910001629 magnesium chloride Inorganic materials 0.000 description 1
206010025482 malaise Diseases 0.000 description 1
230000036210 malignancy Effects 0.000 description 1
230000007246 mechanism Effects 0.000 description 1
238000002483 medication Methods 0.000 description 1
238000002844 melting Methods 0.000 description 1
230000008018 melting Effects 0.000 description 1
239000012528 membrane Substances 0.000 description 1
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
229940016286 microcrystalline cellulose Drugs 0.000 description 1
235000019813 microcrystalline cellulose Nutrition 0.000 description 1
239000008108 microcrystalline cellulose Substances 0.000 description 1
238000002156 mixing Methods 0.000 description 1
150000004712 monophosphates Chemical class 0.000 description 1
238000010172 mouse model Methods 0.000 description 1
239000002324 mouth wash Substances 0.000 description 1
238000007911 parenteral administration Methods 0.000 description 1
235000010603 pastilles Nutrition 0.000 description 1
239000008188 pellet Substances 0.000 description 1
210000005259 peripheral blood Anatomy 0.000 description 1
239000011886 peripheral blood Substances 0.000 description 1
210000005105 peripheral blood lymphocyte Anatomy 0.000 description 1
230000002085 persistent effect Effects 0.000 description 1
238000009520 phase I clinical trial Methods 0.000 description 1
239000008363 phosphate buffer Substances 0.000 description 1
229940080469 phosphocellulose Drugs 0.000 description 1
230000036470 plasma concentration Effects 0.000 description 1
229920003023 plastic Polymers 0.000 description 1
239000004033 plastic Substances 0.000 description 1
229920001592 potato starch Polymers 0.000 description 1
230000003389 potentiating effect Effects 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
230000001681 protective effect Effects 0.000 description 1
239000011541 reaction mixture Substances 0.000 description 1
230000000717 retained effect Effects 0.000 description 1
238000010839 reverse transcription Methods 0.000 description 1
230000002441 reversible effect Effects 0.000 description 1
229960000329 ribavirin Drugs 0.000 description 1
HZCAHMRRMINHDJ-DBRKOABJSA-N ribavirin Natural products O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1N=CN=C1 HZCAHMRRMINHDJ-DBRKOABJSA-N 0.000 description 1
YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 description 1
229960001860 salicylate Drugs 0.000 description 1
230000001568 sexual effect Effects 0.000 description 1
238000007493 shaping process Methods 0.000 description 1
229910052938 sodium sulfate Inorganic materials 0.000 description 1
235000011152 sodium sulphate Nutrition 0.000 description 1
210000004989 spleen cell Anatomy 0.000 description 1
239000007921 spray Substances 0.000 description 1
229910001220 stainless steel Inorganic materials 0.000 description 1
239000010935 stainless steel Substances 0.000 description 1
239000008223 sterile water Substances 0.000 description 1
239000000126 substance Substances 0.000 description 1
239000006228 supernatant Substances 0.000 description 1
FIAFUQMPZJWCLV-UHFFFAOYSA-N suramin Chemical compound OS(=O)(=O)C1=CC(S(O)(=O)=O)=C2C(NC(=O)C3=CC=C(C(=C3)NC(=O)C=3C=C(NC(=O)NC=4C=C(C=CC=4)C(=O)NC=4C(=CC=C(C=4)C(=O)NC=4C5=C(C=C(C=C5C(=CC=4)S(O)(=O)=O)S(O)(=O)=O)S(O)(=O)=O)C)C=CC=3)C)=CC=C(S(O)(=O)=O)C2=C1 FIAFUQMPZJWCLV-UHFFFAOYSA-N 0.000 description 1
229960005314 suramin Drugs 0.000 description 1
239000004094 surface-active agent Substances 0.000 description 1
239000000375 suspending agent Substances 0.000 description 1
239000003765 sweetening agent Substances 0.000 description 1
238000003786 synthesis reaction Methods 0.000 description 1
229940124597 therapeutic agent Drugs 0.000 description 1
LCJVIYPJPCBWKS-NXPQJCNCSA-N thymosin Chemical compound SC[C@@H](N)C(=O)N[C@H](CO)C(=O)N[C@H](CC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(=O)N[C@H](C(C)C)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](C(C)C)C(=O)N[C@H](CO)C(=O)N[C@H](CO)C(=O)N[C@H](CCC(O)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@H]([C@H](C)O)C(=O)N[C@H](C(C)C)C(=O)N[C@H](CCCCN)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N[C@H](CCC(O)=O)C(=O)N[C@H](CCCCN)C(=O)N[C@H](CCCCN)C(=O)N[C@H](CCC(O)=O)C(=O)N[C@H](C(C)C)C(=O)N[C@H](C(C)C)C(=O)N[C@H](CCC(O)=O)C(=O)N[C@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@H](CCC(O)=O)C(O)=O LCJVIYPJPCBWKS-NXPQJCNCSA-N 0.000 description 1
238000011200 topical administration Methods 0.000 description 1
231100000331 toxic Toxicity 0.000 description 1
230000002588 toxic effect Effects 0.000 description 1
238000002723 toxicity assay Methods 0.000 description 1
235000010487 tragacanth Nutrition 0.000 description 1
239000000196 tragacanth Substances 0.000 description 1
229940116362 tragacanth Drugs 0.000 description 1
238000013519 translation Methods 0.000 description 1
125000002264 triphosphate group Chemical group [H]OP(=O)(O[H])OP(=O)(O[H])OP(=O)(O[H])O* 0.000 description 1
230000029812 viral genome replication Effects 0.000 description 1

Landscapes

Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

CA000616284A 1985-03-16 1992-01-13 Nucleosides antiviraux Expired - Fee Related CA1340519C (fr)

Priority Applications (1)

Application Number	Priority Date	Filing Date	Title
CA000616284A CA1340519C (fr)	1985-03-16	1992-01-13	Nucleosides antiviraux

Applications Claiming Priority (12)

Application Number	Priority Date	Filing Date	Title
GB858506869A GB8506869D0 (en)	1985-03-16	1985-03-16	Antiviral compound
GB8506869		1985-03-16
GB8511774		1985-05-09
GB858511774A GB8511774D0 (en)	1985-05-09	1985-05-09	Antiviral compounds
GB776899		1985-09-17
US06/776,899 US4724232A (en)	1985-03-16	1985-09-17	Treatment of human viral infections
GB858523881A GB8523881D0 (en)	1985-09-27	1985-09-27	Antiviral compounds
GB8523881		1985-09-27
GB868603450A GB8603450D0 (en)	1986-02-12	1986-02-12	Antiviral compounds
GB8603450		1986-02-12
CA000556981A CA1303032C (fr)	1985-03-16	1988-01-20	Nucleosides antiviraux
CA000616284A CA1340519C (fr)	1985-03-16	1992-01-13	Nucleosides antiviraux

Related Parent Applications (1)

Application Number	Title	Priority Date	Filing Date
CA000556981A Division CA1303032C (fr)	1985-03-16	1988-01-20	Nucleosides antiviraux

Publications (1)

Publication Number	Publication Date
CA1340519C true CA1340519C (fr)	1999-04-27

Family

ID=33425751

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA000616284A Expired - Fee Related CA1340519C (fr)	1985-03-16	1992-01-13	Nucleosides antiviraux

Country Status (1)

Country	Link
CA (1)	CA1340519C (fr)

1992
- 1992-01-13 CA CA000616284A patent/CA1340519C/fr not_active Expired - Fee Related

Legal Events

Date	Code	Title	Description
2007-04-27	MKLA	Lapsed

Publication	Publication Date	Title
EP0291633B1 (fr)	1992-11-04	Utilisation de la 3'azido-3'-déoxythymidine pour le traitement ou la prophylaxie des infections humaines à rétrovirus
AU622950B2 (en)	1992-04-30	Therapeutic nucleosides
US5071983A (en)	1991-12-10	Therapeutic nucleosides
EP0317128B1 (fr)	1995-12-20	Pyrimidine Nucléosides Anti-HIV
US4920210A (en)	1990-04-24	2,6-diaminopurine-9-β-D-2',3'-dideoxyribofuranoside
EP0306597B1 (fr)	1994-11-02	Nucléosides antiviraux
EP0594223B1 (fr)	2000-03-01	Combination de nucléosides thérapeutiques et d'autre agents thérapeutiques.
CA1340519C (fr)	1999-04-27	Nucleosides antiviraux
JPS61257925A (ja)	1986-11-15	抗ウイルスヌクレオシド
CA1303032C (fr)	1992-06-09	Nucleosides antiviraux
IE56505B1 (en)	1991-08-14	Antiviral nucleosides
IL85096A (en)	1994-02-27	Use of 3'-azido-3'- deoxythymidine in the treatment of prophylaxis of human retrovirus infection
WO1988009332A1 (fr)	1988-12-01	Nucleosides a usage therapeutique
CA1327005C (fr)	1994-02-15	Nucleosides therapeutiques
CA1336821C (fr)	1995-08-29	Nucleosides pour usage therapeutique
EP0294113A1 (fr)	1988-12-07	Nucléosides thérapeutiques
NZ224007A (en)	1991-04-26	3'-azido-3'-deoxythymidine derivatives as antiviral agents
HU197209B (en)	1989-03-28	Process for producing pharmaceutical compositions containing 3'-azido-3'-deoxytimidine of antiviral activity againt human retrovirus
EP0544668A1 (fr)	1993-06-09	-6-fluoro-9-(2,3-didesoxy-b-d-glycero-pentofuranosyl)-9h-purines ainsi que leur emploi en tant qu'agents antiviraux