JPH0544925B2 - - Google Patents
Info
- Publication number
- JPH0544925B2 JPH0544925B2 JP63220346A JP22034688A JPH0544925B2 JP H0544925 B2 JPH0544925 B2 JP H0544925B2 JP 63220346 A JP63220346 A JP 63220346A JP 22034688 A JP22034688 A JP 22034688A JP H0544925 B2 JPH0544925 B2 JP H0544925B2
- Authority
- JP
- Japan
- Prior art keywords
- formula
- virus
- alizarin
- compound
- antiretroviral
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
- -1 dicarboxymethylaminomethyl Chemical group 0.000 claims description 7
- 229940124522 antiretrovirals Drugs 0.000 claims description 6
- 239000003903 antiretrovirus agent Substances 0.000 claims description 6
- 239000004480 active ingredient Substances 0.000 claims description 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
- 150000003839 salts Chemical class 0.000 claims description 3
- 150000004345 1,2-dihydroxyanthraquinones Chemical class 0.000 claims description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 2
- 125000000542 sulfonic acid group Chemical group 0.000 claims description 2
- RGCKGOZRHPZPFP-UHFFFAOYSA-N alizarin Chemical compound C1=CC=C2C(=O)C3=C(O)C(O)=CC=C3C(=O)C2=C1 RGCKGOZRHPZPFP-UHFFFAOYSA-N 0.000 description 15
- 241000700605 Viruses Species 0.000 description 14
- 150000001875 compounds Chemical class 0.000 description 14
- 230000000694 effects Effects 0.000 description 12
- 210000004027 cell Anatomy 0.000 description 10
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 10
- 239000000203 mixture Substances 0.000 description 10
- 241001430294 unidentified retrovirus Species 0.000 description 9
- 102100034343 Integrase Human genes 0.000 description 7
- 108010092799 RNA-directed DNA polymerase Proteins 0.000 description 7
- 239000008187 granular material Substances 0.000 description 7
- 238000002360 preparation method Methods 0.000 description 7
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- 239000001768 carboxy methyl cellulose Substances 0.000 description 6
- 229920002678 cellulose Polymers 0.000 description 6
- 239000001913 cellulose Substances 0.000 description 6
- 235000010980 cellulose Nutrition 0.000 description 6
- 238000002347 injection Methods 0.000 description 6
- 239000007924 injection Substances 0.000 description 6
- PWIGYBONXWGOQE-UHFFFAOYSA-N alizarin complexone Chemical compound O=C1C2=CC=CC=C2C(=O)C2=C1C=C(CN(CC(O)=O)CC(=O)O)C(O)=C2O PWIGYBONXWGOQE-UHFFFAOYSA-N 0.000 description 5
- 230000000798 anti-retroviral effect Effects 0.000 description 5
- 239000002775 capsule Substances 0.000 description 5
- 235000019359 magnesium stearate Nutrition 0.000 description 5
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 4
- 241001107098 Rubiaceae Species 0.000 description 4
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 4
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 4
- 229940105329 carboxymethylcellulose Drugs 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 230000002401 inhibitory effect Effects 0.000 description 4
- BBNQQADTFFCFGB-UHFFFAOYSA-N purpurin Chemical compound C1=CC=C2C(=O)C3=C(O)C(O)=CC(O)=C3C(=O)C2=C1 BBNQQADTFFCFGB-UHFFFAOYSA-N 0.000 description 4
- RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 4
- 235000012239 silicon dioxide Nutrition 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 3
- 229920002261 Corn starch Polymers 0.000 description 3
- 241000196324 Embryophyta Species 0.000 description 3
- 206010020460 Human T-cell lymphotropic virus type I infection Diseases 0.000 description 3
- 241000714260 Human T-lymphotropic virus 1 Species 0.000 description 3
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 241000714474 Rous sarcoma virus Species 0.000 description 3
- 229920002472 Starch Polymers 0.000 description 3
- 229930006000 Sucrose Natural products 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 239000011575 calcium Substances 0.000 description 3
- 229910052791 calcium Inorganic materials 0.000 description 3
- 238000007796 conventional method Methods 0.000 description 3
- 239000008120 corn starch Substances 0.000 description 3
- 229940099112 cornstarch Drugs 0.000 description 3
- 238000012258 culturing Methods 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 239000012153 distilled water Substances 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 3
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 3
- 108020004999 messenger RNA Proteins 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 230000035755 proliferation Effects 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 239000008107 starch Substances 0.000 description 3
- 235000019698 starch Nutrition 0.000 description 3
- 239000005720 sucrose Substances 0.000 description 3
- 208000009746 Adult T-Cell Leukemia-Lymphoma Diseases 0.000 description 2
- 208000016683 Adult T-cell leukemia/lymphoma Diseases 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
- 241000287828 Gallus gallus Species 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
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- 108091034057 RNA (poly(A)) Proteins 0.000 description 2
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 2
- 201000006966 adult T-cell leukemia Diseases 0.000 description 2
- HFVAFDPGUJEFBQ-UHFFFAOYSA-M alizarin red S Chemical compound [Na+].O=C1C2=CC=CC=C2C(=O)C2=C1C=C(S([O-])(=O)=O)C(O)=C2O HFVAFDPGUJEFBQ-UHFFFAOYSA-M 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- 229940084030 carboxymethylcellulose calcium Drugs 0.000 description 2
- 239000003086 colorant Substances 0.000 description 2
- 238000000748 compression moulding Methods 0.000 description 2
- 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 2
- 235000014113 dietary fatty acids Nutrition 0.000 description 2
- 239000007884 disintegrant Substances 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 238000001125 extrusion Methods 0.000 description 2
- 239000000194 fatty acid Substances 0.000 description 2
- 229930195729 fatty acid Natural products 0.000 description 2
- 210000002950 fibroblast Anatomy 0.000 description 2
- 239000000796 flavoring agent Substances 0.000 description 2
- 235000013355 food flavoring agent Nutrition 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- 239000001341 hydroxy propyl starch Substances 0.000 description 2
- 235000013828 hydroxypropyl starch Nutrition 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 208000032839 leukemia Diseases 0.000 description 2
- 239000000314 lubricant Substances 0.000 description 2
- 210000001161 mammalian embryo Anatomy 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- VBHKTXLEJZIDJF-UHFFFAOYSA-N quinalizarin Chemical compound C1=CC(O)=C2C(=O)C3=C(O)C(O)=CC=C3C(=O)C2=C1O VBHKTXLEJZIDJF-UHFFFAOYSA-N 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 2
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 2
- 239000003381 stabilizer Substances 0.000 description 2
- 239000000829 suppository Substances 0.000 description 2
- 239000004094 surface-active agent Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- 239000001226 triphosphate Substances 0.000 description 2
- 235000011178 triphosphate Nutrition 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
- 230000009385 viral infection Effects 0.000 description 2
- 238000005303 weighing Methods 0.000 description 2
- JLPULHDHAOZNQI-ZTIMHPMXSA-N 1-hexadecanoyl-2-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCC\C=C/C\C=C/CCCCC JLPULHDHAOZNQI-ZTIMHPMXSA-N 0.000 description 1
- 244000215068 Acacia senegal Species 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 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
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 241000598436 Human T-cell lymphotropic virus Species 0.000 description 1
- 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 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 239000000020 Nitrocellulose Substances 0.000 description 1
- 206010039491 Sarcoma Diseases 0.000 description 1
- 241000580858 Simian-Human immunodeficiency virus Species 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- 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 1
- 102000004357 Transferases Human genes 0.000 description 1
- 108090000992 Transferases Proteins 0.000 description 1
- 108010067390 Viral Proteins Proteins 0.000 description 1
- 208000036142 Viral infection Diseases 0.000 description 1
- 241000713325 Visna/maedi virus Species 0.000 description 1
- 240000008042 Zea mays Species 0.000 description 1
- 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 1
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 1
- YKTSYUJCYHOUJP-UHFFFAOYSA-N [O--].[Al+3].[Al+3].[O-][Si]([O-])([O-])[O-] Chemical compound [O--].[Al+3].[Al+3].[O-][Si]([O-])([O-])[O-] YKTSYUJCYHOUJP-UHFFFAOYSA-N 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 239000000205 acacia gum Substances 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- ZOJBYZNEUISWFT-UHFFFAOYSA-N allyl isothiocyanate Chemical compound C=CCN=C=S ZOJBYZNEUISWFT-UHFFFAOYSA-N 0.000 description 1
- CEGOLXSVJUTHNZ-UHFFFAOYSA-K aluminium tristearate Chemical compound [Al+3].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CEGOLXSVJUTHNZ-UHFFFAOYSA-K 0.000 description 1
- 229940024546 aluminum hydroxide gel Drugs 0.000 description 1
- 229940063655 aluminum stearate Drugs 0.000 description 1
- SMYKVLBUSSNXMV-UHFFFAOYSA-K aluminum;trihydroxide;hydrate Chemical compound O.[OH-].[OH-].[OH-].[Al+3] SMYKVLBUSSNXMV-UHFFFAOYSA-K 0.000 description 1
- 239000003708 ampul Substances 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000000840 anti-viral effect Effects 0.000 description 1
- 239000003899 bactericide agent Substances 0.000 description 1
- 235000001465 calcium Nutrition 0.000 description 1
- CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 1
- 235000013539 calcium stearate Nutrition 0.000 description 1
- 239000008116 calcium stearate Substances 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 210000000349 chromosome Anatomy 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 239000002299 complementary DNA Substances 0.000 description 1
- 238000007906 compression Methods 0.000 description 1
- 230000006835 compression Effects 0.000 description 1
- 239000012059 conventional drug carrier Substances 0.000 description 1
- 235000005822 corn Nutrition 0.000 description 1
- 235000005687 corn oil Nutrition 0.000 description 1
- 239000002285 corn oil Substances 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 235000019325 ethyl cellulose Nutrition 0.000 description 1
- 229920001249 ethyl cellulose Polymers 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 238000005469 granulation Methods 0.000 description 1
- 230000003179 granulation Effects 0.000 description 1
- 238000009396 hybridization Methods 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N hydrochloric acid Substances Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- 239000008172 hydrogenated vegetable oil Substances 0.000 description 1
- KQSBZNJFKWOQQK-UHFFFAOYSA-N hystazarin Natural products O=C1C2=CC=CC=C2C(=O)C2=C1C=C(O)C(O)=C2 KQSBZNJFKWOQQK-UHFFFAOYSA-N 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 238000005342 ion exchange Methods 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000000865 liniment Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000012669 liquid formulation Substances 0.000 description 1
- 229940031703 low substituted hydroxypropyl cellulose Drugs 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 229960003511 macrogol Drugs 0.000 description 1
- HCWCAKKEBCNQJP-UHFFFAOYSA-N magnesium orthosilicate Chemical compound [Mg+2].[Mg+2].[O-][Si]([O-])([O-])[O-] HCWCAKKEBCNQJP-UHFFFAOYSA-N 0.000 description 1
- 239000000391 magnesium silicate Substances 0.000 description 1
- 229910052919 magnesium silicate Inorganic materials 0.000 description 1
- 235000019792 magnesium silicate Nutrition 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 239000008164 mustard oil Substances 0.000 description 1
- 229920001220 nitrocellulos Polymers 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
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- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
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- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
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- 102000004169 proteins and genes Human genes 0.000 description 1
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- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 229940083466 soybean lecithin Drugs 0.000 description 1
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- 235000012424 soybean oil Nutrition 0.000 description 1
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Landscapes
- Medicines Containing Plant Substances (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Description
［産業上の利用分野］
本発明は、レトロウイルスに起因する各種ウイ
ルス性患者の治療に有効な抗レトロウイルス剤に
関するものである。
［従来の技術および課題］
従来、ウイルスの感染を防止すする手段として
ワクチンの接種による方法が一般的にとられてい
た。
科学技術の発展に伴つて、一部のウイルスに対
してその増殖を抑制する薬剤の開発がすすめられ
ている。
ウイルスのうち、特に最近問題となつている後
天免疫症候群（AIDS）を引き起こす、HIV
（Human Immu deficiency Virus）、成人Ｔ細胞
白血病を引き起こすHTLV−Ｉ（成人Ｔ細胞白血
病ウイルス）等はウイルスのうちレトロウイルス
として知られている。
レトロウイルスはウイルス粒子内に、RNA依
存DNA合成酵素（以下、逆転写酵素と称する）
を含むウイルスであり、以下のようにして増殖し
ている。
宿主細胞に感染後、まずRNAが逆転写酵素
によりDNAに転写される。
このDNAが宿主細胞染色体に組み込まれ、
次いで宿主細胞のRNA合成酵素によつて
mRNAが合成される。
このmRNAにより各種のウイルス蛋白が生
成される。
上記mRNAにより形成された蛋白とゲノム
RNAが結合し、子ウイルスとなつて細胞外に
出る。
このレトロウイルスに起因するヒトの疾病に画
期的な治療効果を有する薬剤は従来存在しておら
ず、そのような薬剤の開発が望まれていた。
［課題を解決するための手段］
本発明者等は種々の植物成分について、抗レト
ロウイルス効果に関する研究を行つた結果、アカ
ネ科植物アカネの赤色色素であるアリザリン
（１，２−ジヒドロキシアンスラキノン）および
その誘導体にに抗レトロウイルス効果のあること
を見いし、本発明を完成するに至つた。
すなわち本発明は、下記式
（式中、R1、R2およびR3は同一または異なつ
て、水素原子または水酸基を表し、R4は水素原
子、スルホン酸基またはジカルボキシメチルアミ
ノメチル基を表す）で表されるアリザン誘導体お
よびその薬理学的に許容しうる塩（以下、式の化
合物と称する）を有効成分とする抗レトロウイル
ス剤である。
式の化合物は、色素としては知られているが、
抗ウイルス効果、特に抗レトロウイルス効果を有
することは従来全く知られていなかつたことであ
る。
本発明の抗レトロウイルス剤の有効成分である
式の化合物は、アカネ科植物アカネより抽出分離
することが容易なアリザリンをそのまま用いる
か、このアリザリンを原料として容易にその誘導
体を得ることができるが、試薬として市販されて
いるものを用いることもきる。
式の化合物の具体例を示すと下記の如くであ
る。
[Industrial Field of Application] The present invention relates to an antiretroviral agent effective in treating patients with various viral infections caused by retroviruses. [Prior Art and Problems] Conventionally, vaccination has generally been used as a means of preventing virus infection. With the development of science and technology, the development of drugs that suppress the proliferation of some viruses is progressing. Among viruses, HIV causes acquired immune syndrome (AIDS), which has recently become a problem.
(Human Immu deficiency Virus), HTLV-I (Adult T-cell leukemia virus), which causes adult T-cell leukemia, and the like are known as retroviruses among viruses. Retroviruses contain RNA-dependent DNA synthase (hereinafter referred to as reverse transcriptase) within their virus particles.
It is a virus containing After infecting a host cell, RNA is first transcribed into DNA by reverse transcriptase. This DNA is integrated into the host cell chromosome,
then by host cell RNA synthase
mRNA is synthesized. Various viral proteins are produced from this mRNA. Protein and genome formed by the above mRNA
The RNA binds and becomes a child virus that exits the cell. There has been no drug that has an innovative therapeutic effect on human diseases caused by this retrovirus, and the development of such a drug has been desired. [Means for Solving the Problems] The present inventors conducted research on the antiretroviral effects of various plant ingredients and found that alizarin (1,2-dihydroxyanthraquinone), which is a red pigment of Rubiaceae, a plant belonging to the Rubiaceae family. and its derivatives have antiretroviral effects, leading to the completion of the present invention. That is, the present invention provides the following formula (In the formula, R 1 , R 2 and R 3 are the same or different and represent a hydrogen atom or a hydroxyl group, and R 4 represents a hydrogen atom, a sulfonic acid group or a dicarboxymethylaminomethyl group) It is an antiretroviral agent containing as an active ingredient a pharmacologically acceptable salt thereof (hereinafter referred to as a compound of the formula). The compound of the formula is known as a pigment, but
It was previously unknown that it had an antiviral effect, especially an antiretroviral effect. The compound of the formula, which is the active ingredient of the antiretroviral agent of the present invention, can be obtained by directly using alizarin, which is easily extracted and separated from Rubiaceae, a plant belonging to the Rubiaceae family, or by using this alizarin as a raw material to easily obtain a derivative thereof. It is also possible to use commercially available reagents. Specific examples of compounds of the formula are as follows.
【表】
［発明の効果］
本発明の抗レトロウイルス剤が抗レトロウイル
ス効果を有することについて実験例を挙げて説明
する。
実験例 １
＜逆転写酵素活性に及ぼす影響＞
以下の組成の反応混合液を調製した。
Γ逆転写酵素（Rous associated virus−２、
宝酒造製） ２単位／ml
Γテンプレート・プライマー複合体としてのポ
リアデニル酸・オリゴチミジル酸複合体［ポリ
アデニル酸polyrA（フアルマシア製）、オリゴ
チミジル酸pdT12-18（フアルマシア製）］
10μｇ／ml
Γトリス塩酸酸（PH8.3） 50mM
Γ塩化カリウム 50mM
Γ塩化マグネシウム 10mM
Γ［3H］デオキシチミジン三リン酸（40Ci／
mmol）（1.0mCi／ml） 0.2μM
Γデオキシチミジン三リン酸 9.8μM
Γ精製水 適量
＊１単位とは、逆転写酵素が37℃、10分間dNTP
（デオキシ核酸三リン酸）1nmolを消費する比活
性単位である。
この反応混合液50μｌを37℃、30分間反応さ
せた。
反応産物DNMの定量はイオン交換濾紙法を用
い、［3H］デオキシチミジン三リン酸のDNAへ
の放射活性の取り込みをベツクマン・シンチレー
シヨンカウンターで測定して、逆転写酵素活性と
し、各被験物における50％阻害濃度（IC50）を算
出した。その結果を第１表に示す。[Table] [Effects of the Invention] The fact that the antiretroviral agent of the present invention has an antiretroviral effect will be explained with reference to experimental examples. Experimental Example 1 <Influence on Reverse Transcriptase Activity> A reaction mixture having the following composition was prepared. Γ reverse transcriptase (Rous associated virus-2,
(manufactured by Takara Shuzo) 2 units/ml Polyadenylic acid/oligothymidylic acid complex as a Γ template/primer complex [polyadenylic acid polyrA (manufactured by Pharmacia), oligothymidylic acid pdT 12-18 (manufactured by Pharmacia)]
10μg/ml ΓTris-hydrochloric acid (PH8.3) 50mM ΓPotassium chloride 50mM ΓMagnesium chloride 10mM Γ[ 3H ]deoxythymidine triphosphate (40Ci/
mmol) (1.0mCi/ml) 0.2μM Γdeoxythymidine triphosphate 9.8μM Γpurified water Appropriate amount
(Deoxynucleic acid triphosphate) It is a specific activity unit that consumes 1 nmol. 50 μl of this reaction mixture was reacted at 37° C. for 30 minutes. The reaction product DNM was quantified using the ion-exchange filter paper method, and the incorporation of radioactivity of [ 3H ]deoxythymidine triphosphate into DNA was measured using a Beckman scintillation counter, which was determined as reverse transcriptase activity. The 50% inhibitory concentration (IC 50 ) was calculated. The results are shown in Table 1.
【表】
実験例 ２
＜ラウス肉腫ウイルス(RSV)による初代ニワトリ
胚繊維芽細胞形質転換に対する抑制効果＞
24穴マイクロプレートに１穴当たり3.5×105細
胞の初代ニワトリ胚繊維芽細胞をいれ、37℃、５
％CO2下で６時間培養した。培養後、この細胞に
RSV・SR−Ａ株、感染多重度（M.O.I）約2.0×
10-4および各被験物質を加え、２時間培養した
後、細胞を洗浄し、更に各被験物質と寒天培地を
加え、37℃、５％CO2下で８日間培養した後、そ
のフオーカス数を測定した。
その結果をIC50で示したのが、第２表である。[Table] Experimental Example 2 <Suppressive effect on transformation of primary chicken embryo fibroblasts by Rous sarcoma virus (RSV)> Place 3.5 x 10 5 primary chicken embryo fibroblasts per well in a 24-well microplate, and °C, 5
Cultured for 6 hours under % CO2 . After culturing, this cell
RSV/SR-A strain, multiplicity of infection (MOI) approximately 2.0×
After adding 10 -4 and each test substance and incubating for 2 hours, the cells were washed, each test substance and agar medium were added, and after culturing for 8 days at 37°C and 5% CO 2 , the focus number was determined. It was measured. Table 2 shows the results in terms of IC50 .
【表】
実験例１および２の結果から本発明の抗レトロ
ウイルス剤の有効成分である式の化合物は、逆転
写酵素活性阻害作用に基づく抗レトロウイルス効
果を有することが確認された。
すなわち式の化合物は、レトロウイルスの増殖
において必要な逆転写酵素活性を阻害することに
より、その増殖を抑制するものであるから、レト
ロウイルスであればいかなるウイルスにも適用す
ることができる。
レトロウイルスの具体例としては、白血病ウイ
ルス、肉腫ウイルス、乳癌ウイルス、ビスナウイ
ルス、マエデイウイルス、HIV、HTLV−Ｉ等
が挙げられる。
更に、式の化合物は逆転移酵素活性を阻害する
だけでなく、レトロウイルス感染細胞のレトロウ
イルス産生能を抑制する作用を有する。
以下にその実験例を示す。
実験例 ３
〈MT−２培養細胞における成人ヒト白血病
ウイルス（HTLV−Ｉ）産生に対する抑制効
果〉
24穴マイクロプレートに１穴当たり１×105細
胞のMT−２細胞と各被験物質をいれ、４日間培
養した。培養後、各穴のMT−２浮遊液を遠心分
離し、その上清をフエノール抽出してHTLV−
ＩのRNAを得た。このRNAと既知量のHTLV
−IcDNAをニトロセルロース紙にブツトし、32P
標識HTLV−IcDNAをプローブとしたハイブリ
ダイゼーシヨン法による比較定量を行い、コント
ロールに対するウイルス産生量との比較から被験
物質の抑制率を算出した。
その結果を抑制率（％）で示したのが、第３表
である。[Table] From the results of Experimental Examples 1 and 2, it was confirmed that the compound of the formula, which is the active ingredient of the antiretroviral agent of the present invention, has an antiretroviral effect based on the inhibitory effect on reverse transcriptase activity. That is, the compound of the formula suppresses the proliferation of retroviruses by inhibiting the reverse transcriptase activity necessary for their proliferation, and therefore can be applied to any retrovirus. Specific examples of retroviruses include leukemia virus, sarcoma virus, breast cancer virus, Visna virus, Maedi virus, HIV, HTLV-I, and the like. Furthermore, the compound of the formula not only inhibits reverse transferase activity but also has the effect of suppressing the ability of retrovirus-infected cells to produce retroviruses. An experimental example is shown below. Experimental Example 3 <Suppressive effect on adult human leukemia virus (HTLV-I) production in cultured MT-2 cells> MT-2 cells and each test substance were placed in a 24-well microplate at a rate of 1 x 105 cells per hole, Cultured for 1 day. After culturing, the MT-2 suspension in each well was centrifuged, the supernatant was extracted with phenol, and HTLV-
RNA of I was obtained. This RNA and a known amount of HTLV
−I cDNA was printed onto nitrocellulose paper and 32 P
Comparative quantification was performed using a hybridization method using labeled HTLV-IcDNA as a probe, and the inhibition rate of the test substance was calculated from the comparison with the amount of virus produced relative to the control. Table 3 shows the results in terms of inhibition rate (%).
【表】
実験例３の結果から式の化合物のレトロウイル
ス感染細胞のレトロウイルス産生能抑制効果が認
められた。
また、アリザリンおよびアリザリンレツトＳ
は、マウスにおける静脈内投与でのLD50がそれ
ぞれ120mg／Kg、70mg／Kgと高いことが知られて
おり、式の化合物は、極めて毒性が低く安全性の
高いものであることがわかる。
次に、式の化合物の投与量および製剤化につい
て説明する。
式の化合物はそのまま、あるいは慣用の製剤担
体と共に動物および人に投与することができる。
投与形態としては、特に限定がなく、必要に応じ
適宜選択として使用され、錠剤、カプセル剤、顆
粒剤、細粒剤、散剤等の径口剤、注射剤、坐剤等
の非経口剤が挙げられる。
経口剤として所期の効果を発揮するためには、
患者の年令、体重、疾患の程度により異なるが、
通常成人で式の化合物の質量として0.1〜６ｇを、
１日数回にわけての服用が適当と思われる。
本発明において錠剤、カプセル剤、顆粒剤等の
経口剤は、例えばデンプン、乳糖、白糖、マンニ
ツト、カルボキシメチルセルロース、コーンスタ
ーチ、無機塩類等を用いて常法に従って製造され
る。
この種の製剤には、適宜前記賦形剤の他に、結
合剤、崩壊剤、界面活性剤、滑尺剤、流動性促進
剤、矯味剤、着色剤、香料等を使用することがで
きる。それぞれの具体例は以下に示す如くであ
る。
［結合剤］
デンプン、テキストリン、アラビアゴム末、ゼ
ラチン、ヒドロキシプロピルスターチ、メチルセ
ルロース、カルボキシメチルセルロースナトリウ
ム、ヒドロキシプロピピルセルロース、結晶セル
ロース、エチルセルロース、ポリビニルピロリド
ン、マクロゴール。
［崩壊剤］
デンプン、ヒドロキシプロピルスターチ、カル
ボキシメチルセルロスナトリウム、カルボキシメ
チルセルロースカルシウム、カルボキシルメチル
セルロース、低置換ヒドロキシプロピルセルロー
ス。
［界面活性剤］
ラウリル硫酸ナトリウム、大豆レシチン、シヨ
糖脂肪酸エステル、ポリソルベート80。
［滑沢剤］
タルク、ロウ類、水素添加植物油、シヨ糖脂肪
酸エステル、ステアリン酸マグネシウム、ステア
リン酸カルシウム、ステアリン酸アルミニウム、
ポリエチレングリコル。
［流動性促進剤］
軽質無水ケイ酸、乾燥水酸化アルミニウムゲ
ル、合成ケイ酸アルミニウム、ケイ酸マグネシウ
ム。
また式の化合物へは、懸濁液、エマルジヨン
剤、シロツプ剤、エリキシル剤としても投与する
ことができ、これらの各種剤形には、矯味矯臭
剤、着色剤を含有してもよい。
非経口剤として所期の効果を発揮するために
は、患者の年令、体重、疾患の程度により異なる
が、通常成人で式の化合物の重量として１日１〜
100mgまでの静注、点滴静注、皮下注射、筋肉注
射が適当と思われる。
この非経口剤は常法に従つて製造され、希釈剤
として一般に注射用蒸留水、生理食塩水、ブドウ
糖水溶液、注射用植物油、ゴマ油、ラツカセイ
油、ダイズ油、トウモロコシ油、プロピレングリ
コール、ポリエチレングリコール等を用いること
ができる。さらに必要に応じて、殺菌剤、防腐
剤、安定剤を加えてもよい。また、この非経口剤
は安定性の点から、バイアル等に充填後冷凍し、
通常の凍結乾燥技術により水分を除去し、使用直
前に凍結乾燥物から液剤を再調製することもでき
る。更に、必要に応じて適宜、等張化剤、安定
剤、防腐剤、無痛化剤等を加えても良い。
その他の非経口剤としては、外用液剤、軟膏等
の塗布剤、直腸内投与のための坐剤等が挙げら
れ、常法に従つて製造される。
実施例 １
コーンスターチ 44ｇ
結晶セルロース 40ｇ
カルボキシメチルセルロースカルシウム ５ｇ
軽質無水ケイ酸 ５ｇ
ステアリン酸マグネシウム 0.5ｇアリザリン 10ｇ
計 100ｇ
上記の処方に従つて〜を均一に混合し、打
錠機にて圧縮成型して一錠200mgの錠剤を得た。
この錠剤一錠には、アリザリン20mgが含有され
ており、成人１日５〜７錠を数回にわけて服用す
る。
実施例 ２
結晶セルロース 84.5ｇ
ステアリン酸マグネシウム 0.5ｇ
カルボキシメチルセルロースカルシウム ５ｇアリザリンコンプレキソン 10ｇ
計 100ｇ
上記の処方に従つて、およびの一部を均
一に混合し、圧縮成型した後、粉砕し、および
の残量を加えて混合し、打錠機にて圧縮成型し
て一錠200mgの錠剤を得た。
この錠剤一錠には、アリザリンコンプレキソン
20mgが含有されており、成人１日５〜７錠を数回
にわけて服用する。
実施例 ３
結晶セルロース 34.5ｇ
10％ヒドロキシプロピルセルロースエタノー
ル溶液 50ｇ
カルボキシメチルセルロースカルシウム ５ｇ
ステアリン酸マグネシウム 0.5ｇアリザリンレツドＳ 10ｇ
計 100ｇ
上記の処方に従つて+、およびを均一に混
合し、常法によりねつ和し、押し出し造粒機によ
り造粒し、乾燥・解砕した後、およびを混合
し、打錠機にて圧縮成型して一錠200mgの錠剤を
得た。
この錠剤一錠には、アリザリンレツドS20mgが
含有されており、成人１日５〜７錠を数回にわけ
て服用する。
実施例 ４
コーンスターチ 84ｇ
ステアリン酸マグネシウム 0.5ｇ
カルボキシチルセルロースカルシウム ５ｇ
軽質無水ケイ酸 0.5ｇキナリザリン 10ｇ
計 100ｇ
上記の処方に従つて〜を均一に混合し、圧
縮成型機にて圧縮成型後、破砕機により粉砕機に
て圧縮成型後、破砕機により粉砕し、篩別して顆
粒剤を得た。
この顆粒剤１ｇには、キナリザリン100mgが含
有されており、成人１日１〜2.5ｇを数回にわて
け服用する。
実施例 ５
結晶セルロース 55ｇ
10％ヒドロキシプロピルセルロースエタノー
ル溶液 35ｇプルプリン 10ｇ
計 100ｇ
上記の処方に従つて〜を均一に混合し、ね
つ和した。押し出し造粒機により造粒後、乾燥
し、篩別して顆粒剤を得た。
この顆粒剤１ｇには、プルプリン100mgが含有
されており、成人１日１〜2.5ｇを数回にわけて
服用する。
実施例 ６
コーンターチ 89.5ｇ
軽質無水ケイ酸 0.5ｇアリザリンコンプレキソン 10ｇ
計 100ｇ
上記の処方に従つて〜を均一に混合し、
200mgを２号カプセルに充填した。
このカプセル剤１カプセルには、アリザリンコ
ンプレキソン20mgが含有されており、成人１日５
〜７カプセルを数回にわけて服用する。
実施例 ７
注射用蒸留水 適量
ブドウ糖 200mgアリザリンコンプレキソン 10mg
全量 15ml
注射用蒸留水におよびを溶解させた後、５
mlのアンプルに注入し、121℃で15分間加圧滅菌
を行つて注射剤を得た。[Table] From the results of Experimental Example 3, it was observed that the compound of the formula had an inhibitory effect on the ability of retrovirus-infected cells to produce retroviruses. Also, alizarin and alizarin let S
is known to have a high LD 50 of 120 mg/Kg and 70 mg/Kg, respectively, when administered intravenously in mice, indicating that the compound of the formula has extremely low toxicity and high safety. Next, the dosage and formulation of compounds of formula will be described. The compounds of the formula can be administered to animals and humans neat or with conventional pharmaceutical carriers.
The dosage form is not particularly limited and may be selected as needed, and may include parenteral preparations such as tablets, capsules, granules, fine granules, powders, etc., injections, and suppositories. It will be done. In order to exert the desired effect as an oral agent,
Although it varies depending on the patient's age, weight, and severity of the disease,
Normally, for an adult, the mass of the compound of the formula is 0.1 to 6 g,
It seems appropriate to take it several times a day. In the present invention, oral preparations such as tablets, capsules, and granules are manufactured according to conventional methods using, for example, starch, lactose, sucrose, mannitol, carboxymethyl cellulose, cornstarch, inorganic salts, and the like. In addition to the excipients mentioned above, binders, disintegrants, surfactants, lubricating agents, fluidity promoters, flavoring agents, coloring agents, fragrances, and the like can be appropriately used in this type of preparation. Specific examples of each are shown below. [Binder] Starch, texturin, gum arabic powder, gelatin, hydroxypropyl starch, methylcellulose, sodium carboxymethylcellulose, hydroxypropylcellulose, crystalline cellulose, ethylcellulose, polyvinylpyrrolidone, macrogol. [Disintegrant] Starch, hydroxypropyl starch, sodium carboxymethyl cellulose, calcium carboxymethyl cellulose, carboxymethyl cellulose, low substituted hydroxypropyl cellulose. [Surfactant] Sodium lauryl sulfate, soybean lecithin, sucrose fatty acid ester, polysorbate 80. [Lubricant] Talc, waxes, hydrogenated vegetable oil, sucrose fatty acid ester, magnesium stearate, calcium stearate, aluminum stearate,
Polyethylene glycol. [Fluidity promoter] Light anhydrous silicic acid, dry aluminum hydroxide gel, synthetic aluminum silicate, magnesium silicate. The compound of the formula can also be administered as a suspension, emulsion, syrup, or elixir, and these various dosage forms may contain flavoring agents and coloring agents. In order to exert the desired effect as a parenteral agent, it is usually necessary for an adult to take 1 to 10% of the weight of the compound of the formula per day, although it varies depending on the age, weight, and severity of the disease of the patient.
Intravenous injections, intravenous drips, subcutaneous injections, and intramuscular injections of up to 100 mg are considered appropriate. This parenteral preparation is manufactured according to a conventional method, and diluents generally include distilled water for injection, physiological saline, aqueous glucose solution, vegetable oil for injection, sesame oil, mustard oil, soybean oil, corn oil, propylene glycol, polyethylene glycol, etc. can be used. Furthermore, a bactericide, a preservative, and a stabilizer may be added as necessary. In addition, from the standpoint of stability, this parenteral preparation is frozen after being filled into vials, etc.
The liquid formulation can also be reconstituted from the lyophilizate immediately prior to use by removing moisture by conventional lyophilization techniques. Furthermore, isotonizing agents, stabilizers, preservatives, soothing agents, etc. may be added as appropriate. Other parenteral preparations include liquid preparations for external use, liniments such as ointments, and suppositories for intrarectal administration, which are manufactured according to conventional methods. Example 1 Cornstarch 44g Crystalline cellulose 40g Carboxymethyl cellulose calcium 5g Light anhydrous silicic acid 5g Magnesium stearate 0.5g Alizarin 10g Total 100g Mix ~ uniformly according to the above recipe, compress and mold using a tablet machine to form one tablet. Obtained 200mg tablets. Each tablet contains 20 mg of alizarin, and adults should take 5 to 7 tablets a day in several doses. Example 2 Crystalline cellulose 84.5g Magnesium stearate 0.5g Calcium carboxymethyl cellulose 5g Alizarin complexone 10g Total 100g According to the above recipe, a part of and was mixed uniformly, compression molded, and crushed, and the remaining of and was The mixture was added and mixed, and compressed using a tablet machine to obtain tablets each weighing 200 mg. This tablet contains Alizarin Complexone
It contains 20 mg, and adults should take 5 to 7 tablets a day in several doses. Example 3 Crystalline cellulose 34.5g 10% hydroxypropylcellulose ethanol solution 50g Carboxymethylcellulose calcium 5g Magnesium stearate 0.5g Alizarin Red S 10g Total 100g According to the above recipe, + and were mixed uniformly and mixed in a conventional manner. The mixture was mixed, and then granulated using an extrusion granulator, dried and crushed, and then compressed using a tablet machine to obtain tablets each weighing 200 mg. Each tablet contains 20 mg of Alizarin Red S, and adults should take 5 to 7 tablets a day in several doses. Example 4 Cornstarch 84g Magnesium stearate 0.5g Calcium carboxytyl cellulose 5g Light anhydrous silicic acid 0.5g Quinalizarin 10g Total 100g Mix ~ uniformly according to the above recipe, compress and mold with a compression molding machine, and then crush with a crusher After compression molding using a crusher, the mixture was crushed using a crusher and sieved to obtain granules. 1 g of this granule contains 100 mg of quinalizarin, and adults should take 1 to 2.5 g in several doses a day. Example 5 Crystalline cellulose 55g 10% hydroxypropylcellulose ethanol solution 35g Purpurin 10g Total 100g ~ were mixed uniformly according to the above recipe and were made into a paste. After granulation using an extrusion granulator, the mixture was dried and sieved to obtain granules. 1 g of this granule contains 100 mg of purpurin, and adults should take 1 to 2.5 g per day in several doses. Example 6 Corn tarch 89.5g Light anhydrous silicic acid 0.5g Alizarin complexone 10g Total 100g Mix ~ uniformly according to the above recipe,
200 mg was filled into No. 2 capsules. Each capsule contains 20 mg of alizarin complexone, which is 5 mg per day for adults.
Take ~7 capsules in several doses. Example 7 Distilled water for injection Appropriate amount Glucose 200 mg Alizarin complexone 10 mg Total amount 15 ml After dissolving and in distilled water for injection,
The mixture was injected into a ml ampoule and autoclaved at 121°C for 15 minutes to obtain an injection.
Claims (1)
て、水素原子または水酸基を表し、R4は水素原
子、スルホン酸基またはジカルボキシメチルアミ
ノメチル基を表す）で表されるアリザリン誘導体
およびその薬理学的に許容しうる塩を有効成分と
する抗レトロウイルス剤。[Claims] 1. The following formula Alizarin derivative represented by (wherein R 1 , R 2 and R 3 are the same or different and represent a hydrogen atom or a hydroxyl group, and R 4 represents a hydrogen atom, a sulfonic acid group or a dicarboxymethylaminomethyl group) and an antiretroviral agent containing a pharmacologically acceptable salt thereof as an active ingredient.
Priority Applications (6)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP63220346A JPH0269415A (en) | 1988-09-05 | 1988-09-05 | Anti-retrovirus agent |
| AT88907791T ATE87204T1 (en) | 1987-12-10 | 1988-09-12 | ANTI-RETROVIRAL DRUG. |
| PCT/JP1988/000919 WO1989005141A1 (en) | 1987-12-10 | 1988-09-12 | Anti-retroviral drug |
| DE8888907791T DE3879688T2 (en) | 1987-12-10 | 1988-09-12 | ANTI-RETROVIRAL MEDICINAL PRODUCT. |
| EP88907791A EP0348509B1 (en) | 1987-12-10 | 1988-09-12 | Anti-retroviral drug |
| KR1019890701470A KR920003577B1 (en) | 1987-12-10 | 1988-09-12 | Anti-retroviral drug |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP63220346A JPH0269415A (en) | 1988-09-05 | 1988-09-05 | Anti-retrovirus agent |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH0269415A JPH0269415A (en) | 1990-03-08 |
| JPH0544925B2 true JPH0544925B2 (en) | 1993-07-07 |
Family
ID=16749701
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP63220346A Granted JPH0269415A (en) | 1987-12-10 | 1988-09-05 | Anti-retrovirus agent |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH0269415A (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH02270824A (en) * | 1989-04-13 | 1990-11-05 | Snow Brand Milk Prod Co Ltd | Reverse transcriptase inhibitor |
-
1988
- 1988-09-05 JP JP63220346A patent/JPH0269415A/en active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| JPH0269415A (en) | 1990-03-08 |
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