JPH03181420A - Antiviral agent - Google Patents
Antiviral agentInfo
- Publication number
- JPH03181420A JPH03181420A JP32034089A JP32034089A JPH03181420A JP H03181420 A JPH03181420 A JP H03181420A JP 32034089 A JP32034089 A JP 32034089A JP 32034089 A JP32034089 A JP 32034089A JP H03181420 A JPH03181420 A JP H03181420A
- Authority
- JP
- Japan
- Prior art keywords
- oligosaccharide
- antiviral agent
- salt
- residue
- galactose
- 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.)
- Pending
Links
- 239000003443 antiviral agent Substances 0.000 title claims abstract description 15
- 229920001542 oligosaccharide Polymers 0.000 claims abstract description 46
- 150000002482 oligosaccharides Chemical class 0.000 claims abstract description 45
- 239000004480 active ingredient Substances 0.000 claims abstract description 11
- 150000003839 salts Chemical class 0.000 claims abstract description 9
- 125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 claims abstract description 7
- 125000002791 glucosyl group Chemical group C1([C@H](O)[C@@H](O)[C@H](O)[C@H](O1)CO)* 0.000 claims abstract description 6
- 125000004043 oxo group Chemical group O=* 0.000 claims abstract description 3
- 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 abstract description 8
- 241000700605 Viruses Species 0.000 abstract description 8
- 230000002401 inhibitory effect Effects 0.000 abstract description 8
- 239000008101 lactose Substances 0.000 abstract description 8
- 208000030507 AIDS Diseases 0.000 abstract description 5
- 150000001875 compounds Chemical class 0.000 abstract description 4
- 102000005936 beta-Galactosidase Human genes 0.000 abstract description 3
- 108010005774 beta-Galactosidase Proteins 0.000 abstract description 3
- 230000035755 proliferation Effects 0.000 abstract description 2
- 230000001180 sulfating effect Effects 0.000 abstract description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 abstract 2
- 208000035473 Communicable disease Diseases 0.000 abstract 1
- 229910006069 SO3H Inorganic materials 0.000 abstract 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 abstract 1
- WQZGKKKJIJFFOK-PHYPRBDBSA-N alpha-D-galactose Chemical compound OC[C@H]1O[C@H](O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-PHYPRBDBSA-N 0.000 abstract 1
- 230000003013 cytotoxicity Effects 0.000 abstract 1
- 231100000135 cytotoxicity Toxicity 0.000 abstract 1
- 201000010099 disease Diseases 0.000 abstract 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract 1
- 230000001747 exhibiting effect Effects 0.000 abstract 1
- 230000002538 fungal effect Effects 0.000 abstract 1
- 229930182830 galactose Natural products 0.000 abstract 1
- 235000014655 lactic acid Nutrition 0.000 abstract 1
- 239000004310 lactic acid Substances 0.000 abstract 1
- 230000003612 virological effect Effects 0.000 abstract 1
- 210000004027 cell Anatomy 0.000 description 13
- 239000000203 mixture Substances 0.000 description 13
- 238000006243 chemical reaction Methods 0.000 description 12
- 238000000034 method Methods 0.000 description 8
- XTHPWXDJESJLNJ-UHFFFAOYSA-N sulfurochloridic acid Chemical compound OS(Cl)(=O)=O XTHPWXDJESJLNJ-UHFFFAOYSA-N 0.000 description 8
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- 239000002904 solvent Substances 0.000 description 5
- -1 sulfate ester Chemical class 0.000 description 5
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- 206010028980 Neoplasm Diseases 0.000 description 4
- 201000011510 cancer Diseases 0.000 description 4
- 239000002552 dosage form Substances 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- NBTMNFYXJYCQHQ-UHFFFAOYSA-N (2,3,4,5,6-pentasulfooxycyclohexyl) hydrogen sulfate Chemical compound OS(=O)(=O)OC1C(OS(O)(=O)=O)C(OS(O)(=O)=O)C(OS(O)(=O)=O)C(OS(O)(=O)=O)C1OS(O)(=O)=O NBTMNFYXJYCQHQ-UHFFFAOYSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 230000000840 anti-viral effect Effects 0.000 description 3
- 230000005779 cell damage Effects 0.000 description 3
- 208000037887 cell injury Diseases 0.000 description 3
- 238000007796 conventional method Methods 0.000 description 3
- 239000013078 crystal Substances 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 239000000796 flavoring agent Substances 0.000 description 3
- 235000013355 food flavoring agent Nutrition 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
- 230000035484 reaction time Effects 0.000 description 3
- 150000004043 trisaccharides Chemical class 0.000 description 3
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 2
- 208000009746 Adult T-Cell Leukemia-Lymphoma Diseases 0.000 description 2
- 208000016683 Adult T-cell leukemia/lymphoma Diseases 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 208000031886 HIV Infections Diseases 0.000 description 2
- 208000037357 HIV infectious disease Diseases 0.000 description 2
- 241000222068 Sporobolomyces <Sporidiobolaceae> Species 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- 201000006966 adult T-cell leukemia Diseases 0.000 description 2
- 150000003863 ammonium salts Chemical class 0.000 description 2
- 230000001580 bacterial effect Effects 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 230000000120 cytopathologic effect Effects 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 235000021255 galacto-oligosaccharides Nutrition 0.000 description 2
- 150000003271 galactooligosaccharides Chemical class 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 208000033519 human immunodeficiency virus infectious disease Diseases 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 150000002772 monosaccharides Chemical class 0.000 description 2
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 238000005670 sulfation reaction Methods 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- 229920002683 Glycosaminoglycan Polymers 0.000 description 1
- 239000004378 Glycyrrhizin Substances 0.000 description 1
- SQUHHTBVTRBESD-UHFFFAOYSA-N Hexa-Ac-myo-Inositol Natural products CC(=O)OC1C(OC(C)=O)C(OC(C)=O)C(OC(C)=O)C(OC(C)=O)C1OC(C)=O SQUHHTBVTRBESD-UHFFFAOYSA-N 0.000 description 1
- 241000714260 Human T-lymphotropic virus 1 Species 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 206010061598 Immunodeficiency Diseases 0.000 description 1
- 208000029462 Immunodeficiency disease Diseases 0.000 description 1
- 229920000057 Mannan Polymers 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- FYUNWJFIWFVVBT-UHFFFAOYSA-H S(=O)(=O)([O-])[O-].[K+].[K+].[K+].[K+].[K+].[K+].S(=O)(=O)([O-])[O-].S(=O)(=O)([O-])[O-] Chemical compound S(=O)(=O)([O-])[O-].[K+].[K+].[K+].[K+].[K+].[K+].S(=O)(=O)([O-])[O-].S(=O)(=O)([O-])[O-] FYUNWJFIWFVVBT-UHFFFAOYSA-H 0.000 description 1
- 229920002125 Sokalan® Polymers 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 208000036142 Viral infection Diseases 0.000 description 1
- 229930003270 Vitamin B Natural products 0.000 description 1
- 231100000215 acute (single dose) toxicity testing Toxicity 0.000 description 1
- 238000011047 acute toxicity test Methods 0.000 description 1
- 108010025925 alarin Proteins 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 235000011114 ammonium hydroxide Nutrition 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000036436 anti-hiv Effects 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 238000009835 boiling Methods 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
- 239000008116 calcium stearate Substances 0.000 description 1
- 235000013539 calcium stearate Nutrition 0.000 description 1
- 229940041514 candida albicans extract Drugs 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- XTHPWXDJESJLNJ-UHFFFAOYSA-M chlorosulfate Chemical compound [O-]S(Cl)(=O)=O XTHPWXDJESJLNJ-UHFFFAOYSA-M 0.000 description 1
- 230000001112 coagulating effect Effects 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 238000004891 communication Methods 0.000 description 1
- 210000000805 cytoplasm Anatomy 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 229960002086 dextran Drugs 0.000 description 1
- 229960000633 dextran sulfate Drugs 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 238000002651 drug therapy Methods 0.000 description 1
- 238000000921 elemental analysis Methods 0.000 description 1
- 239000012156 elution solvent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 125000002519 galactosyl group Chemical group C1([C@H](O)[C@@H](O)[C@@H](O)[C@H](O1)CO)* 0.000 description 1
- LPLVUJXQOOQHMX-UHFFFAOYSA-N glycyrrhetinic acid glycoside Natural products C1CC(C2C(C3(CCC4(C)CCC(C)(CC4C3=CC2=O)C(O)=O)C)(C)CC2)(C)C2C(C)(C)C1OC1OC(C(O)=O)C(O)C(O)C1OC1OC(C(O)=O)C(O)C(O)C1O LPLVUJXQOOQHMX-UHFFFAOYSA-N 0.000 description 1
- 229960004949 glycyrrhizic acid Drugs 0.000 description 1
- UYRUBYNTXSDKQT-UHFFFAOYSA-N glycyrrhizic acid Natural products CC1(C)C(CCC2(C)C1CCC3(C)C2C(=O)C=C4C5CC(C)(CCC5(C)CCC34C)C(=O)O)OC6OC(C(O)C(O)C6OC7OC(O)C(O)C(O)C7C(=O)O)C(=O)O UYRUBYNTXSDKQT-UHFFFAOYSA-N 0.000 description 1
- 235000019410 glycyrrhizin Nutrition 0.000 description 1
- LPLVUJXQOOQHMX-QWBHMCJMSA-N glycyrrhizinic acid Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@H](O[C@@H]1O[C@@H]1C([C@H]2[C@]([C@@H]3[C@@]([C@@]4(CC[C@@]5(C)CC[C@@](C)(C[C@H]5C4=CC3=O)C(O)=O)C)(C)CC2)(C)CC1)(C)C)C(O)=O)[C@@H]1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O LPLVUJXQOOQHMX-QWBHMCJMSA-N 0.000 description 1
- 230000007813 immunodeficiency Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 229960000367 inositol Drugs 0.000 description 1
- CDAISMWEOUEBRE-GPIVLXJGSA-N inositol Chemical compound O[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@H](O)[C@@H]1O CDAISMWEOUEBRE-GPIVLXJGSA-N 0.000 description 1
- 238000004255 ion exchange chromatography Methods 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 231100001083 no cytotoxicity Toxicity 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 231100000572 poisoning Toxicity 0.000 description 1
- 230000000607 poisoning effect Effects 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 239000004584 polyacrylic acid Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- CDAISMWEOUEBRE-UHFFFAOYSA-N scyllo-inosotol Natural products OC1C(O)C(O)C(O)C(O)C1O CDAISMWEOUEBRE-UHFFFAOYSA-N 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- UDYFLDICVHJSOY-UHFFFAOYSA-N sulfur trioxide pyridine complex Chemical compound O=S(=O)=O.C1=CC=NC=C1 UDYFLDICVHJSOY-UHFFFAOYSA-N 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 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
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000008399 tap water Substances 0.000 description 1
- 235000020679 tap water Nutrition 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 235000019156 vitamin B Nutrition 0.000 description 1
- 239000011720 vitamin B Substances 0.000 description 1
- 150000003722 vitamin derivatives Chemical class 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 210000005253 yeast cell Anatomy 0.000 description 1
- 239000012138 yeast extract Substances 0.000 description 1
Landscapes
- Saccharide Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
【発明の詳細な説明】
（産業上の利用分野）
本発明は、特定のオリゴ糖誘導体及びその塩を有効成分
として含有する抗ウィルス剤に関するものであり、これ
は、ウィルス性疾患の治療や予防等に好適に使用できる
。Detailed Description of the Invention (Field of Industrial Application) The present invention relates to an antiviral agent containing a specific oligosaccharide derivative and its salt as an active ingredient. It can be suitably used for etc.
（従来の技術）
これまで、抗ウイルス効果をもつ化合物が多数報告され
ており、また近年、特に世界的な広がりを見せ始めた後
天性免疫不全症候群（ＡＩＤＳ）の病原ウィルス（ｌｌ
ｕｍａｎ Ｉｍｍｕｎｏｄｅｆｉｃｉｅｎｃｙ Ｖｉｒ
ｕｓ。(Prior Art) Many compounds with antiviral effects have been reported, and in recent years, the pathogenic virus (III) of acquired immunodeficiency syndrome (AIDS), which has begun to spread worldwide, has been reported.
uman Immunodeficiency Vir
us.
ＨＩＶ）に対して抗ウイルス効果を示す化合物の探索が
活発に行われている。それらの例として。The search for compounds that exhibit antiviral effects against HIV is actively underway. As an example of them.
ポリアクリル酸及びデキストランサルフェート等［Ｄｅ
ＳｏｍｅｒＰ、ら；ジャーナル・オブ・ピロロジー（
Ｊ、 Ｖｉｒｏｌ、） １９６８． ２． ８７８．同
誌１９６８． ２゜８８６：］、スラミン（Ｄｅ Ｃ１
ａｒｃｑ Ｂ、 ：カンサー・レター（Ｃａｎｃｅｒ
Ｌｅｔｔｅｒ） １９７９． ８． ９ ： Ｍｉｔｓ
ｕｙａＨ，う；サイエンス（Ｓｃｉｅｎｃｅ） （ワシ
ントン・デイ−・シー）１９Ｂ４，２２６．１？２１．
エバンス・ブルー（：Ｒａ１ｚａｒｉｎｉ Ｊ、ら
；インターナショナル−ジャーナル・オブ・カンサー（
Ｉｎｔ、Ｊ、 Ｃａｎｃｅｒ）１９８６．３？、４５１
Ｌ アラリンカルボン酸〔Ｂａ１ｚａｒｉｎｉ Ｊ、
ら；バイオケミカル・アンド・バイオフイジイカル・リ
サーチ・コミュニケーション（Ｂｉｏｃｈｅｍ、Ｂｉｏ
ｐｈｙｓ、 Ｒｅｓ、Ｃｏｍｍｕｎ、）１９８６ 、
１３６゜６４，１．３°−アジド−２′、３”−ジデ
オキシチミジン（ＡＺＴ） ［Ｍｉｔｓｕｙａ Ｈ，ら
；プロシーディング・ナショナル・アカデミ−・オブ・
サイエンス（Ｐｒｏｃ、 Ｎａｔｉ、 Ａｃａｄ、 Ｓ
ｃｉ、Ｕ、Ｓ、Ａ、） １９８６． ８３． １９１１
〕、グリチルリチン（伊藤正彦ら；第３４回日本ライス
ル学会総会講演要旨集１９８６． Ｐ ７０）。Polyacrylic acid and dextran sulfate etc. [De
SomerP, et al.; Journal of Pyrology (
J, Virol, ) 1968. 2. 878. Same magazine 1968. 2゜886: ], Suramin (De C1
arcq B, :Cancer Letter
Letter) 1979. 8. 9: Mits
Science (Washington DC) 19B4, 226.1?21.
Evans Blue (: Ra1zarini J, et al.; International Journal of Cancer)
Int, J, Cancer) 1986.3? , 451
L alarin carboxylic acid [Ba1zarini J,
et al; Biochemical and Biophysical Research Communication (Biochem, Bio
phys, Res, Commun,) 1986,
136°64,1.3°-azido-2′,3”-dideoxythymidine (AZT) [Mitsuya H, et al.; Proceedings National Academy of Sciences
Science (Proc, Nati, Acad, S
ci, U, S, A,) 1986. 83. 1911
], glycyrrhizin (Masahiko Ito et al.; Abstracts of the 34th Annual Meeting of the Japanese Lysl Society, 1986. P. 70).
グルチルリチン硫酸塩（特開昭６３−２４３０９３号公
報）、デキストラン、キシロフラナン及びリボフラナン
の硫酸エステル〔Ｎａｋａｓｈｉｍａ Ｈ，ら；日本ジ
ャーナル・カンサー・リサーチ（Ｊａｐａｎ Ｊ。Glucyrrhizin sulfate (JP-A-63-243093), sulfate esters of dextran, xylofuranan and ribofuranan [Nakashima H, et al.; Japan Journal Cancer Research (Japan J.
Ｃａｎｃｅｒ Ｒｅｓ、） １９８７．７８． １１６
４：ｌ 、マンナン硫酸エステル（特開昭６４−５２７
２３号公報）。Cancer Res, ) 1987.78. 116
4:l, mannan sulfate ester (JP-A-64-527
Publication No. 23).
単糖及び三糖誘導体（特開平１−１４９７３０号公報）
、天然ムコ多糖類の硫酸エステル（特開昭６３−４５２
２３号公報）等が報告されている。Monosaccharides and trisaccharide derivatives (JP-A-1-149730)
, natural mucopolysaccharide sulfate ester (JP-A-63-452
Publication No. 23) etc. have been reported.
（発明が解決しようとする課題）
しかしながら、これらの抗ウィルス剤は、その抗ウイル
ス効果が十分なものでないという問題があった。(Problems to be Solved by the Invention) However, these antiviral agents have a problem in that their antiviral effects are not sufficient.
本発明は、上記のような従来技術の問題を克服するもの
で、実用上優れた抗ウィルス剤を提供することを目的と
するものである。The present invention overcomes the problems of the prior art as described above, and aims to provide a practically excellent antiviral agent.
（課題を解決するための手段）
本発明者らは、このような課題を解決するために鋭意検
討した結果、特定のオリゴ糖誘導体が従来の抗ウィルス
剤に比べ有効性にすぐれていることを見出し、この知見
に基づいて本発明をなすに至った。(Means for Solving the Problems) As a result of intensive studies to solve these problems, the present inventors have found that certain oligosaccharide derivatives are more effective than conventional antiviral agents. Based on this finding, the present invention has been made.
すなわち２本発明は、一般式Ｇａｐ−（Ｇａｌｎ−Ｇｌ
ｃＣただし９式中Ｇａｊ？はガラクトース残基、Ｇｊ２
ｃはグルコース残基、ｎは１〜４の整数をそれぞれ表す
。）で示されるオリゴ糖に、少なくとも１個のスルホ基
（−３○３Ｈ）が、ガラクトース残基あるいはグルコー
ス残基のオキソ基（−〇−）を介して結合されているオ
リゴ糖誘導体又はその塩を有効成分とする抗ウィルス剤
を要旨とするものである。That is, 2 the present invention is based on the general formula Gap-(Galn-Gl
cC However, Gaj in formula 9? is a galactose residue, Gj2
c represents a glucose residue, and n represents an integer of 1 to 4, respectively. ) An oligosaccharide derivative or a salt thereof, in which at least one sulfo group (-3○3H) is bonded to the oligosaccharide represented by ) via an oxo group (-○-) of a galactose residue or a glucose residue The gist is an antiviral agent containing as an active ingredient.
以下１本発明の詳細な説明する。The present invention will be explained in detail below.
本発明で用いられるオリゴ糖としては、上記の一般式中
、ｎが１〜４．すなわち、３〜６糖類であれば、特に限
定されるものでなく、又これらのオリゴ糖のうちどれか
１種類が単独でもあってもあるいは任意の二種以上の組
合せからなるオリゴ糖の混合物であってもよい。As the oligosaccharide used in the present invention, in the above general formula, n is 1 to 4. In other words, it is not particularly limited as long as it is a trisaccharide to hexasaccharide, and any one of these oligosaccharides may be used alone or a mixture of two or more oligosaccharides may be used. There may be.
また１本発明で用いられるオリゴ糖における糖残基間の
結合様式としては、特に限定されるものではなく、β−
１，３結合、β−１．４結合、β−■。Furthermore, the bonding mode between sugar residues in the oligosaccharide used in the present invention is not particularly limited, and β-
1,3 bond, β-1.4 bond, β-■.
６結合等どのようなものでもよい。Any type of bond such as 6 bonds may be used.
本発明の抗ウィルス剤の有効成分であるオリコ糖誘導体
としては、上記したオリゴ糖に、少なくとも■個のスル
ホ基（−３○３Ｈ）が、ガラクトース残基あるいはグル
コース残基のオキソ基（−〇−）を介して結合されてい
ればよく、結合されるスルホ基の個数あるいは結合位置
には特に限定されるものではない。The oligosaccharide derivative that is the active ingredient of the antiviral agent of the present invention is such that the oligosaccharide described above has at least -), and there are no particular limitations on the number or bonding positions of the sulfo groups to be bonded.
上記したオリゴ糖誘導体は、必要に応じて薬理的に許容
し得る塩であってもよく１例えばスルホ基がカリウム、
ナトリウム等のアルカリ金属塩あるいはアンモニウム塩
になっていてもよい。これらの塩は常法によって容易に
製造することができる。The above oligosaccharide derivative may be a pharmacologically acceptable salt if necessary. For example, the sulfo group may be potassium,
It may be an alkali metal salt such as sodium or an ammonium salt. These salts can be easily produced by conventional methods.
本発明の抗ウィルス剤の有効成分であるオリコ糖誘導体
又はその塩を製造するには、まず、上記したようなオリ
ゴ糖を製造し９次いで得られたオリゴ糖をサルフェート
化するという方法が採用できる。In order to produce the oligosaccharide derivatives or salts thereof that are the active ingredients of the antiviral agent of the present invention, a method can be adopted in which the oligosaccharides as described above are first produced and then the obtained oligosaccharides are sulfated. .
上記したようなオリゴ糖を製造するには、ラクトースに
β−ガラクトシダーゼあるいは乳糖資化能を有する酵母
菌体を作用させるという公知の方法が採用できる。これ
らの方法は、特公昭５８２０２６６号公報、特開昭６３
−１８５３７３号公報及び中村ら；生物化学実験法１９
．澱粉・関連糖質実験法（学会出版センター）Ｐ２Ｓ５
等に記載されている方法に従えばよい。その−例として
は、以下のようにすることができる。In order to produce the above-mentioned oligosaccharides, a known method can be employed in which lactose is treated with β-galactosidase or yeast cells capable of assimilating lactose. These methods are described in Japanese Patent Publication No. 5820266 and Japanese Patent Application Laid-open No. 63
-185373 Publication and Nakamura et al.; Biochemical Experimental Methods 19
．． Starch and related carbohydrate experimental methods (Society Publishing Center) P2S5
You can follow the method described in, etc. An example of this can be as follows.
乳糖４０重量％水溶液に、市販酵素β−ガラクトシダー
ゼ（例えば、新日本化学社製Ｓｕｍｙｌａｃｔ■）を３
．３ｍｇ％になるように添加し、ｐＨを約５に調整後、
約４０℃で４時間反応させることにより。A commercially available enzyme β-galactosidase (for example, Sumylact■ manufactured by Shin Nihon Kagaku Co., Ltd.) was added to a 40% by weight lactose aqueous solution.
．． After adding it to 3 mg% and adjusting the pH to about 5,
By reacting at about 40°C for 4 hours.
ガラクトシル基の転移生成物であるオリゴ糖を製造する
ことができる。Oligosaccharides, which are transfer products of galactosyl groups, can be produced.
このようにして得られたオリゴ糖の３〜６糖類の構成比
及び結合様式の構成比は、ラクトース濃度、酵素量１反
応時間９反応温度等の反応条件によって変化し、これら
の反応条件を適当な条件に設定することにより、任意の
種類及び結合様式のオリゴ糖を得ることができる。The composition ratio of trisaccharides to hexasaccharides and the composition ratio of the binding mode of the oligosaccharide thus obtained vary depending on reaction conditions such as lactose concentration, enzyme amount, reaction time, reaction temperature, etc., and these reaction conditions can be adjusted as appropriate. By setting appropriate conditions, oligosaccharides of any type and binding mode can be obtained.
例えば、酵素量を増やし反応時間を長くすると。For example, if you increase the amount of enzyme and lengthen the reaction time.
５及び６糖類の構成比を高くさせるとともに、β−１，
３結合、β−１，６結合の結合様式の割合を木きくさせ
ることができる。In addition to increasing the composition ratio of pentasaccharides and hexasaccharides, β-1,
The ratio of bonding modes of 3 bonds and β-1,6 bonds can be adjusted.
このようにして得られたオリゴ糖を反応液から分離する
には１周知の方法が採用でき２例えば。In order to separate the oligosaccharide obtained in this way from the reaction solution, a well-known method can be used, for example.
活性炭カラムクロマトグラフィーを用いることができる
。Activated carbon column chromatography can be used.
以上のようにして得られたオリゴ糖は、各種類のオリゴ
糖に単離された後、あるいは二種以上混合されたそのま
まで次のサルフェート化反応に用いることができる。The oligosaccharides obtained as described above can be used in the next sulfation reaction after being isolated into various types of oligosaccharides, or as a mixture of two or more types.
サルフェート化反応としては２周知の方法が採用でき１
例えば、ピリジン中でオリゴ糖に過剰量のクロル硫酸を
加えればよい。また、この条件で反応が激しい場合には
、クロル硫酸を１．２−ジクロロエタンやクロロホルム
といった溶媒に混ぜ。2. Well-known methods can be used for the sulfation reaction.1
For example, an excess amount of chlorosulfate may be added to the oligosaccharide in pyridine. If the reaction is intense under these conditions, mix chlorosulfuric acid with a solvent such as 1,2-dichloroethane or chloroform.
これに、オリゴ糖と塩基としてのピリジン等が加えられ
ているジメチルスルホキシド（ＤＭＳ○）又は、ジメチ
ルホルムアミド（ＤＭＦ）溶液を滴下するという混合溶
媒系で反応を行うこともできる。ここで用いられる２種
類の溶媒は、１つはその溶媒中でクロル硫酸が安定であ
ればよく、もう１つは、オリゴ糖が溶ける極性溶媒であ
ればよい。The reaction can also be carried out in a mixed solvent system in which a dimethyl sulfoxide (DMS○) or dimethyl formamide (DMF) solution to which an oligosaccharide and a base such as pyridine are added is added dropwise. The two types of solvents used here may be one as long as chlorosulfuric acid is stable therein, and the other as long as it is a polar solvent in which the oligosaccharide can be dissolved.
そして、さらにこれら２種類の溶媒は、互いに混ざり合
うものであればよい。また９反応温度としては、室温で
も水浴中での冷却下でもよく、用いる溶媒の沸点と融点
の間であればよい。反応時間としては９反応温度が低く
、温和な条件では長くなるが２通常２時間で十分に反応
は終了する。Further, these two types of solvents may be used as long as they are miscible with each other. Further, the reaction temperature may be room temperature or cooling in a water bath, as long as it is between the boiling point and melting point of the solvent used. As for the reaction time, 9 the reaction temperature is low and the reaction takes a long time under mild conditions, but the reaction is usually completed within 2 hours.
上記したクロル硫酸以外のサルフェート化剤としては、
ピペリジン−Ｎ−硫酸〔特開昭６１−１３０３０１号公
報、特開昭６１−１３０３０２号公報及びに、 ｔｌａ
ｔａｎａｋａら；ジャーナル・メディカル・ケミストリ
ー（Ｊ、 Ｍｅｄ、Ｃｈｅｍ） １９８７． ３０．
８１０〕あるいはサルファトリオキサイド−ピリジン（
３０３・ＣｓＨｓＮ） ［：ＢａｕｍｇａｌｔｅｎＰ、
；ベリッヒテ（Ｂｅｒ、） １９２６． ５９． １
１６０〕等が挙げられる。Sulfating agents other than the above-mentioned chlorosulfuric acid include:
Piperidine-N-sulfuric acid [JP-A-61-130301, JP-A-61-130302, and tla
Tanaka et al.; Journal Medical Chemistry (J, Med, Chem) 1987. 30.
810] or sulfur trioxide-pyridine (
303・CsHsN) [:BaumgaltenP,
; Berichte (Ber,) 1926. 59. 1
160] etc.
このようにして得られた反応液からオリゴ糖誘導体を単
離するには１通常使用される手段、・例えば、抽出、イ
オン交換クロマトグラフィー、再結晶、薄層クロマトグ
ラフィー等の方法を、単独または組合せて採用すればよ
い。To isolate the oligosaccharide derivative from the reaction solution obtained in this way, 1. Usually used means, such as extraction, ion exchange chromatography, recrystallization, thin layer chromatography, etc., can be used alone or They can be used in combination.
本発明の抗ウィルス剤の有効成分であるオリゴ糖誘導体
又はその塩は、エイズの原因ウィルスであるＨＩＶを感
染させたＭＴ−４細胞（成人Ｔ細胞白血病の原因ウィル
スであるＨＴＬＶ−１陽性細胞株）の細胞障害に対して
、すぐれた抑制効果を示す。The oligosaccharide derivative or its salt, which is the active ingredient of the antiviral agent of the present invention, is used in MT-4 cells (HTLV-1 positive cell line, the causative virus of adult T-cell leukemia) infected with HIV, the virus that causes AIDS. ) exhibits excellent inhibitory effects on cell damage.
本発明の抗ウィルス剤は、その使用目的に応じて種々の
投与形態９例えば錠剤、乳剤、カプセル剤、頚粒剤、液
剤、注射剤、シロップ剤、軟膏剤等に製剤化することが
できる。これらの製剤化方法としては９周知の方法が採
用でき１例えば、経口用固形製剤を調製するには、有効
成分に賦形剤及び必要に応じて結合剤、崩壊剤、滑沢剤
２Ｍ色剤、矯味剤、矯臭剤等を加えた後、常法により錠
剤、丸剤、カプセル剤、顆粒剤などに作成することがで
きる。また、液状製剤を調製するには、有効成分に矯味
剤、安定化剤等を加えたのち、常法により液剤、注射剤
などに作成することができる。The antiviral agent of the present invention can be formulated into various dosage forms such as tablets, emulsions, capsules, granules, solutions, injections, syrups, and ointments depending on the purpose of use. 9 Well-known methods can be used to formulate these formulations.1 For example, to prepare solid oral preparations, the active ingredients are combined with excipients and, if necessary, a binder, a disintegrant, a lubricant, and a 2M coloring agent. After adding flavoring agents, flavoring agents, etc., tablets, pills, capsules, granules, etc. can be prepared by conventional methods. In addition, in order to prepare a liquid preparation, a flavoring agent, a stabilizer, etc. are added to the active ingredient, and then a liquid preparation, an injection preparation, etc. can be prepared by a conventional method.
本発明の抗ウィルス剤の投与形態中に配合される有効成
分の含有量としては、使用目的、症状あるいは剤形等に
より一定ではないが、一般には。The content of the active ingredient contained in the dosage form of the antiviral agent of the present invention varies depending on the purpose of use, symptoms, dosage form, etc., but in general.
１〜８５（ｌｖ／Ｗ）％カ望マシイ。1 to 85 (lv/w)% strength.
本発明の抗ウィルス剤の一日当たりの投与量は使用目的
、症状、病状、投与回数１年齢１体重あるいは剤形等に
より一定ではないが１通常、有効成分が体重ＩＫｇ当た
り０．１〜１０００ｍｇとなるようにするのが望ましい
。The daily dosage of the antiviral agent of the present invention is not constant depending on the purpose of use, symptoms, medical conditions, number of doses, age, body weight, dosage form, etc.1 Usually, the active ingredient is 0.1 to 1000 mg per IKg of body weight. It is desirable to do so.
（実施例） 以下１本発明を実施例により具体的に説明する。(Example) The present invention will be specifically explained below using examples.
参考例１
下記組成の培地を３０Ａ容ジャーファーメンタ−に入れ
殺菌した。Reference Example 1 A medium having the following composition was placed in a 30 A jar fermenter and sterilized.
乳糖 ４０００ｇ
酵母エキス ６０ｇ
ＫＨ２Ｐ０． ２０ ｇＭ、ＳＯ，・７
Ｈ２０１０ｇ
ビタミンＢ＋ ６０ｍｇビタミン
Ｂｓ ６０ｍｇ水
２ＯＡ次に、同組成の培地で２８
℃で９６時間前培養したスポロボロミセス・シンギュラ
ス（３ｐｏｒｏｂｏｌｏｍｙｃｅｓ ｓｉｎｇｕｌａｒ
ｉｓ）ＡＴＣＣ２４１９３菌株１１を接種して、ｐＨ３
，５７，温度２８℃１通気量２Ｑ ｊｉ！ ／ｍｉｎ、
インペラー回転数４０ Ｏｒ、ｐｏｍ、で９６時間培
養を行った。Lactose 4000g Yeast extract 60g KH2P0. 20 gM, SO, 7
H2010g Vitamin B+ 60mg Vitamin Bs 60mg water
2OA, then 28 in a medium with the same composition.
3. Sporobolomyces singular precultured at ℃ for 96 hours.
is) inoculated with ATCC24193 strain 11 and adjusted to pH 3
,57,Temperature 28℃ 1 Airflow 2Q ji! /min,
Culture was performed for 96 hours at an impeller rotation speed of 40 Or, pom.
培養終了後α−ラバル社製遠心機ＬＡＰＸ ２０２型で
遠心分離を行って湿菌体２．３ｋｇを得た。After completion of the culture, centrifugation was performed using a centrifuge model LAPX 202 manufactured by α-Laval to obtain 2.3 kg of wet bacterial cells.
実施例１
（ａ） オリゴ糖の製造
４００ｇの乳糖に、参考例１で得たスポロボロミセス・
シンギュラスＡＴＣＣ２４１９３菌株の湿菌体３０ｇを
加え、更に水道水を加え１１とした。この液を５５℃に
保温し、ｐＨ４，５で２日間反応を行った。反応終了後
の液の遠心上澄液５０−を１０１容活性炭カラムにかけ
、エタノールを溶出溶媒としてガラクトオリゴ糖３．８
ｇを単離した。このガラクトオリゴ糖を１３Ｃ−ＮＭＲ
により分析したところ、○−β−Ｄ−ガラクトピラノシ
ルー（１→４）−〇−β−Ｄ−ガラクトピラノシルー（
１→４）−Ｄ−グルコースであった。Example 1 (a) Production of oligosaccharide Sporobolomyces obtained in Reference Example 1 was added to 400 g of lactose.
30 g of wet bacterial cells of Singulus ATCC24193 strain were added, and tap water was further added to make a total of 11. This solution was kept at 55°C and reacted at pH 4.5 for 2 days. After the completion of the reaction, 50 - centrifuged supernatant liquid was applied to a 101 volume activated carbon column, and 3.8 g of galacto-oligosaccharide was added using ethanol as an elution solvent.
g was isolated. 13C-NMR of this galactooligosaccharide
When analyzed by
1→4)-D-glucose.
ら）オリゴ糖誘導体の製造
（ａ）で得られたオリゴ糖粉末１．３ｇをジメチルスル
ホキシド（ＤＭＳ○）５０ｍｆに溶解し、さらにピリジ
ンｌｒｄを加えた。このＤＭＳ○溶液を、クロル硫酸５
−を加えた１、２−ジクロロエタン５〇−中に攪拌下、
冷却しながら徐々に滴下した。室温にて一晩攪拌した後
、溶媒を留去し、油状の残留物をシリカゲル・クロマト
（クロロホルム／メタノール＝５／１）にて精製し、
オリゴ糖誘導体を含む両分にアンモニア水を加えてｐＨ
を８とし。(a) Production of oligosaccharide derivatives 1.3 g of the oligosaccharide powder obtained in (a) was dissolved in 50 mf of dimethyl sulfoxide (DMS○), and pyridine lrd was added. Add this DMS○ solution to chlorosulfuric acid
- in 1,2-dichloroethane 50- with stirring,
It was gradually added dropwise while cooling. After stirring overnight at room temperature, the solvent was distilled off, and the oily residue was purified using silica gel chromatography (chloroform/methanol = 5/1).
Add ammonia water to both parts containing oligosaccharide derivatives to adjust the pH.
Let's take it as 8.
析出した結晶を凝集後、酢酸エチルで洗浄し、結晶０．
８ｇを得た。After coagulating the precipitated crystals, the crystals were washed with ethyl acetate and the crystals were 0.
8g was obtained.
ここで得られたオリゴ糖誘導体を元素分析及び３Ｃ−Ｎ
ＭＲで分析したところ、３糖のオリゴ糖に１１個のスル
ホ基の結合した下記のような構造のものが主成分であっ
た。The oligosaccharide derivative obtained here was subjected to elemental analysis and 3C-N
MR analysis revealed that the main component was a trisaccharide oligosaccharide with 11 sulfo groups bonded to it with the following structure.
〔Ｒはスルホ基（−３○３Ｈ）のアンモニウム塩である
。〕
（Ｃ） オリゴ糖誘導体の薬理効果試験成人Ｔ細胞白
血病の原因ウィルスの陽性細胞株であるＭＴ−４細胞に
、エイズの原因ウィルスであるＨＩＶを感染させると、
細胞質内にＨＩＶの抗原タンパク質が出現し、細胞のＤ
ＮＡ合或が抑制され、細胞変性効果（ＣＰＥ）により、
感染細胞が死滅していく現象を利用して、抗ＨＩＶ効果
を判定する方法により試験した。[R is an ammonium salt of a sulfo group (-3○3H). (C) Pharmacological effect test of oligosaccharide derivatives When MT-4 cells, a cell line positive for the virus that causes adult T-cell leukemia, are infected with HIV, the virus that causes AIDS,
HIV antigen protein appears in the cytoplasm, and the cell's D
NA association is suppressed and due to cytopathic effect (CPE),
The anti-HIV effect was tested using the phenomenon that infected cells die.
つまり、ＭＴ−４細胞にＨＩＶを感染させた後。That is, after infecting MT-4 cells with HIV.
所定の濃度になるようにら）で得られたオリゴ糖誘導体
を添加し、６日間培養した。６日後に生存細胞数を観察
することにより、ＨＩＶ感染による細胞障害がどの程度
抑制されるかを測定した。The oligosaccharide derivative obtained in 1) was added to the mixture to a predetermined concentration, and the mixture was cultured for 6 days. By observing the number of viable cells after 6 days, the extent to which cell damage caused by HIV infection was suppressed was determined.
この実験は、 Ｈａｒａｄａ Ｓ、ら；サイエンス（３
ｃｉｅｎｃｅＨ９８５，２２９，５６３〜５６６に記載
された方法に従って行った。This experiment was carried out by Harada S, et al. Science (3
It was carried out according to the method described in Science H985, 229, 563-566.
対照薬としては、単糖の硫酸化物であるイノシトール６
硫酸６カリウム塩（米国シグマ社製）を用いた。The control drug was inositol 6, a sulfated monosaccharide.
Hexapotassium sulfate salt (manufactured by Sigma, USA) was used.
得られた結果を第１図に示した。第１図中の■はＨＩＶ
感染のＭＴ−４細胞に対する効果を示し。The results obtained are shown in FIG. ■ in Figure 1 indicates HIV
The effect of infection on MT-4 cells is shown.
また７口はＨＩＶ非感染のＭＴ−４細胞に対する効果を
示す。In addition, 7 cells show the effect on MT-4 cells not infected with HIV.
第１図より、対照のイノシトール６硫酸塩が２゜５ ｍ
ｇ ／ ｍ１以上でＨＴＶ障害抑制効果が認められたの
に対し、オリゴ糖誘導体では０．５ｍｇ／−以上の濃度
と、イノシトール６硫酸塩の１１５の低濃度でも抑制効
果をもつことがわかる。また、１０ｍｇ／ｍＩ！の濃度
でも細胞毒性を示さず、有効濃度幅が広い。From Figure 1, the control inositol hexasulfate was 2°5 m
While the inhibitory effect on HTV damage was observed at concentrations of 0.5 mg/ml or more, oligosaccharide derivatives were found to have inhibitory effects even at concentrations as low as 115 for inositol hexasulfate and at concentrations of 0.5 mg/- or higher. Also, 10mg/mI! It exhibits no cytotoxicity even at concentrations of
（ｄ） 急性毒性試験結果
上記オリゴ糖誘導体をマウスについて４００〜２５００
ｍｇ／Ｋｇの範囲で非経口投与（静注及び復往）した
ところ、中毒例及び致死例は見られなかった。従って、
上記オリゴ糖誘導体は極めて低毒性であった。(d) Acute toxicity test results
When administered parenterally (intravenously and reciprocally) in the mg/Kg range, no cases of poisoning or death were observed. Therefore,
The above oligosaccharide derivative had extremely low toxicity.
（ｅ） 製剤化
上記オリゴ糖誘導体カリウム塩２０ｇ、デンプン３８ｇ
、乳糖４０ｇ及びステアリン酸カルシウム２ｇを十分に
混合した後、これを打錠機にかけ１錠５００ｍｇの錠剤
を成型した。得られた錠剤１錠には上記オリゴ糖誘導体
カリウム塩が１００ｍｇ含有されていた。(e) Formulation 20 g of potassium salt of the above oligosaccharide derivative, 38 g of starch
After thoroughly mixing 40 g of lactose and 2 g of calcium stearate, the mixture was put into a tablet machine to form tablets each weighing 500 mg. One tablet obtained contained 100 mg of the oligosaccharide derivative potassium salt.
（発明の効果）
本発明の薬物は、極めて微量でウィルスの増殖を十分に
抑制するので、ウィルス感染症の進行と発症の阻止、治
療および予防を目的とする薬物療法において極めて有効
な手段として使用に供することができる。(Effects of the Invention) The drug of the present invention sufficiently suppresses the proliferation of viruses in extremely small amounts, so it can be used as an extremely effective means in drug therapy aimed at inhibiting, treating, and preventing the progression and onset of viral infections. It can be provided to
第１図は、ＨＩＶ感染による細胞障害に対するオリゴ糖
誘導体の抑制効果をイノシトール６硫酸塩（従来の技術
）と比較した図である。FIG. 1 is a diagram comparing the inhibitory effect of oligosaccharide derivatives on cell damage caused by HIV infection with that of inositol hexasulfate (prior art).
Claims (1)
ＳＯ＿３Ｈ）が、ガラクトース残基あるいはグルコース
残基のオキソ基（−Ｏ−）を介して結合されているオリ
ゴ糖誘導体又はその塩を有効成分とする抗ウィルス剤。(1) An oligosaccharide represented by the following general formula Gal-(Gal)_n-Glc (wherein, Gal represents a galactose residue, Glc represents a glucose residue, and n represents an integer from 1 to 4, respectively.) , at least one sulfo group (-
An antiviral agent containing as an active ingredient an oligosaccharide derivative or a salt thereof in which SO_3H) is bonded via an oxo group (-O-) of a galactose residue or a glucose residue.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP32034089A JPH03181420A (en) | 1989-12-08 | 1989-12-08 | Antiviral agent |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP32034089A JPH03181420A (en) | 1989-12-08 | 1989-12-08 | Antiviral agent |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH03181420A true JPH03181420A (en) | 1991-08-07 |
Family
ID=18120388
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP32034089A Pending JPH03181420A (en) | 1989-12-08 | 1989-12-08 | Antiviral agent |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH03181420A (en) |
-
1989
- 1989-12-08 JP JP32034089A patent/JPH03181420A/en active Pending
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