JPH02275819A - Antiviral agent on aids virus - Google Patents
Antiviral agent on aids virusInfo
- Publication number
- JPH02275819A JPH02275819A JP34012089A JP34012089A JPH02275819A JP H02275819 A JPH02275819 A JP H02275819A JP 34012089 A JP34012089 A JP 34012089A JP 34012089 A JP34012089 A JP 34012089A JP H02275819 A JPH02275819 A JP H02275819A
- Authority
- JP
- Japan
- Prior art keywords
- aids
- hiv
- antiviral agent
- acid
- effective
- 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 8
- 241000700605 Viruses Species 0.000 title claims description 15
- 208000030507 AIDS Diseases 0.000 claims abstract description 20
- 239000002253 acid Substances 0.000 claims abstract description 9
- 239000004480 active ingredient Substances 0.000 claims abstract description 4
- 230000000840 anti-viral effect Effects 0.000 abstract description 6
- 208000015181 infectious disease Diseases 0.000 abstract description 5
- 125000000129 anionic group Chemical group 0.000 abstract description 2
- 210000004369 blood Anatomy 0.000 abstract description 2
- 239000008280 blood Substances 0.000 abstract description 2
- 230000037396 body weight Effects 0.000 abstract description 2
- 231100000331 toxic Toxicity 0.000 abstract description 2
- 230000002588 toxic effect Effects 0.000 abstract description 2
- 241000725303 Human immunodeficiency virus Species 0.000 abstract 2
- 150000001875 compounds Chemical class 0.000 abstract 1
- 210000005260 human cell Anatomy 0.000 abstract 1
- 238000002560 therapeutic procedure Methods 0.000 abstract 1
- 210000004027 cell Anatomy 0.000 description 10
- 241000713340 Human immunodeficiency virus 2 Species 0.000 description 8
- 230000002401 inhibitory effect Effects 0.000 description 8
- 230000000694 effects Effects 0.000 description 6
- 102100034343 Integrase Human genes 0.000 description 5
- 108010092799 RNA-directed DNA polymerase Proteins 0.000 description 5
- 241001430294 unidentified retrovirus Species 0.000 description 4
- 230000000120 cytopathologic effect Effects 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 101900297506 Human immunodeficiency virus type 1 group M subtype B Reverse transcriptase/ribonuclease H Proteins 0.000 description 2
- 239000000427 antigen Substances 0.000 description 2
- 102000036639 antigens Human genes 0.000 description 2
- 108091007433 antigens Proteins 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 208000002672 hepatitis B Diseases 0.000 description 2
- -1 nasal preparations Substances 0.000 description 2
- 230000003612 virological effect Effects 0.000 description 2
- 206010001985 Amoebic colitis Diseases 0.000 description 1
- 201000002909 Aspergillosis Diseases 0.000 description 1
- 208000036641 Aspergillus infections Diseases 0.000 description 1
- 108020004414 DNA Proteins 0.000 description 1
- 208000001388 Opportunistic Infections Diseases 0.000 description 1
- 206010035664 Pneumonia Diseases 0.000 description 1
- 241000384942 Premna serratifolia Species 0.000 description 1
- 206010039491 Sarcoma Diseases 0.000 description 1
- 208000000389 T-cell leukemia Diseases 0.000 description 1
- 208000028530 T-cell lymphoblastic leukemia/lymphoma Diseases 0.000 description 1
- 210000001744 T-lymphocyte Anatomy 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 230000036436 anti-hiv Effects 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000002784 cytotoxicity assay Methods 0.000 description 1
- 231100000263 cytotoxicity test Toxicity 0.000 description 1
- 230000007850 degeneration Effects 0.000 description 1
- WZRZTHMJPHPAMU-UHFFFAOYSA-L disodium;(3e)-3-[(4-amino-3-sulfonatophenyl)-(4-amino-3-sulfophenyl)methylidene]-6-imino-5-methylcyclohexa-1,4-diene-1-sulfonate Chemical compound [Na+].[Na+].C1=C(S([O-])(=O)=O)C(=N)C(C)=CC1=C(C=1C=C(C(N)=CC=1)S([O-])(=O)=O)C1=CC=C(N)C(S(O)(=O)=O)=C1 WZRZTHMJPHPAMU-UHFFFAOYSA-L 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 241001493065 dsRNA viruses Species 0.000 description 1
- 238000000684 flow cytometry Methods 0.000 description 1
- 201000005787 hematologic cancer Diseases 0.000 description 1
- 208000024200 hematopoietic and lymphoid system neoplasm Diseases 0.000 description 1
- 208000006454 hepatitis Diseases 0.000 description 1
- 231100000283 hepatitis Toxicity 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 231100001231 less toxic Toxicity 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 229940037525 nasal preparations Drugs 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 230000002250 progressing effect Effects 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- NQLVQOSNDJXLKG-UHFFFAOYSA-N prosulfocarb Chemical compound CCCN(CCC)C(=O)SCC1=CC=CC=C1 NQLVQOSNDJXLKG-UHFFFAOYSA-N 0.000 description 1
- 230000010076 replication Effects 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 230000001629 suppression Effects 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
- 208000011580 syndromic disease Diseases 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 230000007442 viral DNA synthesis Effects 0.000 description 1
Landscapes
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
Description
【発明の詳細な説明】
［産業上の利用分野］
本発明は、現在までに治療法が知られていないエイズの
原因ウィルスに対して有効な抗ウィルス剤に関する。DETAILED DESCRIPTION OF THE INVENTION [Industrial Application Field] The present invention relates to an antiviral agent that is effective against the virus that causes AIDS, for which no treatment is known so far.
［従来の技術］
抗ウィルス作用を有するウィルス剤は、アラ−ニー（Ａ
ｒｓ−Ａ）、アシクロビール（Ａｃｙｃｌｏｗｉｔ）な
どのようにウィルスのＤＮＡ合成阻害作用のもの、レト
ロウィルスなどの逆転写酵素の阻害作用をもつスラミン
（！ｆｎｒｇｍｉｎ）、リバビリン（Ｒｉｂｕｉｒｉｎ
）、ニーゼット・ティー （ＡｚＴ、 Ａｔｉｄｏｔｈ
７ｍｉｄｉｎｅ）などが知られている。[Prior art] A viral agent with antiviral action is Arani (A
rs-A), Acyclowit, etc., which have an inhibitory effect on viral DNA synthesis, suramin (!fnrgmin), which has an inhibitory effect on reverse transcriptase, such as retroviruses, and Ribuirin.
), Kneesed Tea (AzT, Atidoth)
7midine) etc. are known.
レトロウィルスは、ＲＮＡからＤＮＡへの転写を逆転写
酵素で行なうＲＮＡウィルスである。エイズ（Ａ Ｉ
Ｄ Ｓ （Ａｃｑｕｉｒｅｄ Ｉｍｍｕｎｅ Ｄｅｆｉ
ｃｉｅｎｃ７Ｓ７ｎｄｒｏｍｅ ：後天性免疫不全症候
群）］原因ウィルスはレトロウィルスであって、ＨＴＬ
Ｖ−［［（Ｈｕｍａｎ Ｔ ｃｅｌＪ Ｌ７ｍｐｈｏｔ
ｒｏｐｂｉｅ Ｖｉｒｕｓ） 、ＬＡＶ（Ｌ７ｍｐｈｚ
ｄｅｎｏｐｇｔｂｙ ｔｓｓｏｃｉａｔｅｄ Ｖｉｒｕ
ｓ）またはＨＩ Ｖ （ｈｍａｎ １ｕｉｕｉｏｄｅｆ
ｉｃｉｅｎｃ７ ｖｉｒｕｓ） と呼ばれる。Retroviruses are RNA viruses that use reverse transcriptase to transcribe RNA into DNA. AIDS (AI)
D S (Acquired Immune Defi
cienc7S7ndrome: Acquired Immune Deficiency Syndrome)] The causative virus is a retrovirus, and HTL
V-[[(Human T celJ L7mphot
ropbie Virus), LAV (L7mphz
denopgtby tssociated Viru
s) or HIV (hman 1uiuiodef
icienc7 virus).
エイズは、生体の免疫低下により、カボシ肉腫、カリニ
肺炎、カンシタ感染、アスペルギルス感染、アメーバ大
腸炎などの日和見感染により生じるもので、現在までに
ＡＺＴはＨＩＶの増殖を抑える薬剤として知られている
に過ぎない。AIDS is caused by opportunistic infections such as Kabosi's sarcoma, carinii pneumonia, Cancissa infection, Aspergillus infection, and amoebic colitis due to a weakened body's immune system, and AZT is currently known as a drug that suppresses the proliferation of HIV. Not too much.
エイズ原因ウィルスの感染後、ＡＣ（Ａｓ７ｍｐｔｏｍ
１目ｃ Ｃｅｒｒｉｅｔ）からＡＲＣ（ＡＩＤＳ Ｒｅ
１ａｔｃｄ Ｃｏｍｐｌｅｘ）を経てエイズとなること
が知られている。After infection with the AIDS-causing virus, AC (As7mptom)
1st c Cerriet) to ARC (AIDS Re
1atcd Complex), which leads to AIDS.
［発明が解決しようとする問題点］
抗ウィルス物質として、逆転写酵素の阻害物質として作
用するものは、正常な細胞群に対する毒性、生体への副
作用が強く、投与による延命作用の他に生体の衰弱が生
じる。[Problems to be solved by the invention] Antiviral substances that act as inhibitors of reverse transcriptase are toxic to normal cell groups and have strong side effects on living organisms, and in addition to prolonging life when administered, they also have adverse effects on living organisms. Weakness occurs.
本発明は、毒性の少ない逆転写酵素の阻害作用およびそ
の他のメカニズムを持つ物質により、ＡＲＣへの進展、
エイズの治療およびエイズ原因ウィルスの細胞への感染
を抑制し、エイズへの到達を阻害する治療剤を提供する
ことを目的とするものである。The present invention aims to promote the development of ARC by using a substance that has a less toxic reverse transcriptase inhibitory effect and other mechanisms.
The purpose of this invention is to treat AIDS and to provide a therapeutic agent that suppresses the infection of cells by the virus that causes AIDS and prevents the development of AIDS.
［問題点を解決するための手段］
本発明は、フクシン酸を有効成分とするエイズ原因ウィ
ルスに対する抗ウィルス剤である。[Means for Solving the Problems] The present invention is an antiviral agent against the AIDS-causing virus, which contains fuchsic acid as an active ingredient.
本発明に用いられるフクシン酸はアニオン染料であって
、下記の化学構造を有するものである。Fuchsic acid used in the present invention is an anionic dye and has the following chemical structure.
Ｈ２
その投与量は、１６μｍでＨＩ Ｖの抗ウィルス作用が
みられたことよりヒト血中でも同程度で有効と考えられ
、体重６０ｋｇあたり２■〜１ｇの投与で効果が期待で
きる。Since the antiviral effect of H2 was observed at 16 μm, it is considered to be effective at the same level in human blood, and an effect can be expected with administration of 2 to 1 g per 60 kg of body weight.
本抗ウイルス剤中には安定化剤などを含んでもよく、剤
型としては、注射剤、カプセル剤、経鼻剤、座薬、経口
薬、軟膏剤など、種々の形態のものが用いられる。The antiviral agent may contain a stabilizer and the like, and various dosage forms are used, such as injections, capsules, nasal preparations, suppositories, oral preparations, and ointments.
［実 験 例］
（Ａ）ヒトＴ細胞系（Ｈｕｍａｎ Ｔ４ Ｌ７ｍｐｂ
ｏｃ７ｆｅ Ｌｉｎｅ）
ＭＴ−４、ＨＵＴ−７８を培養し、ＨＩＶタイプ１ （
ＨＩＶ−１） 、ＨＩＶタイプ２（ＨＩＶ−２）などの
エイズ原因ウィルスを感染させ、Ａｎｔｉ−ＨＩＶアッ
セイとして、エイズ原因ウィルスの複製（ｒｅｐｌｉｃ
ａｔｉｏｎ）を細胞の変性（ｃ７ｔｏｐｘｔｈｏｇｅｎ
ｆｃｉｔ７）で検討した。また、ウィルス抗原をフロー
サイトメトリーで解析した。[Experimental example] (A) Human T cell line (Human T4 L7mpb
oc7fe Line) MT-4 and HUT-78 were cultured, and HIV type 1 (
HIV type 2 (HIV-1), HIV type 2 (HIV-2), and other AIDS-causing viruses are infected, and the replication of the AIDS-causing virus is detected as an Anti-HIV assay.
ation) and cell degeneration (c7topxthogen).
fcit7). In addition, viral antigens were analyzed by flow cytometry.
さらに、細胞毒性検定（Ｃ７ｔｏｔｏｘｉｃｉ１７ ａ
ｓｓａ７）はＬＳ１２１０、ＦＭ３Ａ、Ｒａｊ ｉ、Ｍ
ｏ ｌ ｔ／４ＦＸＣＥＭなどの細胞を用いて、バルザ
リニ（Ｂａｌｘｘｒｉｎｉ）による方法［Ｂａ１ｚａｒ
ｉｎｉ、 Ｊ５．ＤｅＣＩｅｒｃｑ、 Ｅ、 丁ｏｒ
ｒｅｎｃｅ、 Ｐ、Ｆ、、 ）ｌｅｒｌｅｓ、Ｍ、
Ｐ、Ｐｉｒｋ。In addition, cytotoxicity assay (C7toxic17a
ssa7) is LS1210, FM3A, Raji, M
The method according to Balzarini [Ba1zar
ini, J5. DeCIercq, E, Dingor
rence, P, F,,)lerles, M,
P, Pirk.
Ｊ、Ｓ、、 Ｓｃｈｍｉｄｌ、 Ｃ，Ｌ、、 Ｓ
ｈｕｇａｒ、 Ｄ、、Ｂａｒｔ、 Ｐ、Ｊ、。J.S., Schmidl, C.L., S.
hugar, D., Bart, P.J.
Ｊｏｎｅｓ、 Ａ、Ｓ、、 Ｙｅｒｈｅｌｓ［、Ｇ
、 ｌｎｄ Ｗａｌｋｅｒ、 ＲｏＴ。Jones, A.S., Yerhels[,G.
, lnd Walker, RoT.
（１９８２） Ｂｉｏｃｈｅｎ＋、 Ｐｂａｔｎ＋ａｃ
ｏｌ、 ３１．１０８９−１０９５．およびＢｇｌｓａ
ｒｉｎｉ、 Ｊ、、旧ｔｓｕｙｌ、 Ｈ，、ＤｅＣｌ
ｅｒｃｑ、 Ｅ。(1982) Biochen+, Pbatn+ac
ol, 31.1089-1095. and Bglsa
rini, J., former tsuyl, H., DeCl
ercq, E.
ｓｏｄ Ｂｒｏｄｅｒ、 Ｓ、 （１９８６） Ｂ
ｉｏｃｈｅｍ、 Ｂｉｏｐｈ７ｓ、 Ｒｅｓ。sod Broder, S. (1986) B
iochem, Bioph7s, Res.
ｏｍｍｕｎ、 １３６． ６４−７１． ）で行なっ
た。ommun, 136. 64-71. ).
逆転写酵素とウィルスの吸着についても検討した。Adsorption of reverse transcriptase and viruses was also investigated.
（Ｂ）エイズ原因ウィルス感染細胞に対するフクシン酸
の効果
エイズ原因ウィルスであるＨＩＶ−１に対する抑制効果
は、細胞変性（ＣＰ Ｅ）の完全抑制については１２５
μｍ、ＥＤ５．は４２．ｃｚｍ（表−１）、ＨＩ Ｖ−
２に対してはそのＥ Ｄ ｓ ａが６３μｍであった。(B) Effect of fuchsic acid on cells infected with the AIDS-causing virus The inhibitory effect on HIV-1, the AIDS-causing virus, is 125
μm, ED5. is 42. czm (Table-1), HIV-
2, its E D sa was 63 μm.
さらにＨＩＶ抗原の抑制は２５μｍ、ＥＤ５ｏは１６μ
ｍであった。Furthermore, the suppression of HIV antigen is 25 μm, and the ED5o is 16 μm.
It was m.
以下余白
表Ｉ ＭＴ−４とＨＵＴ−７８細胞に対するフクシン
の酸の抵ＨＩＶ効果
ａ ５０％抗ウィルス効果
ｂ ５Ｇ％細胞変性作用
Ｃ選択値（ｓｅｌｅｃｔｉｙｅ １ｎｄｅｘ）ｄ Ａ
ｕｒｉｎｔｒｉｃａｒｂｏｒ７１ｉｃ ａｃｉｄ第１図
にフクシン酸の細胞変性阻止効果を示す。Margin Table I Below: HIV-resistant effect of fuchsin acid on MT-4 and HUT-78 cells a 50% antiviral effect b 5G% cytopathic effect C selection value (selectiye 1ndex) d A
urintric acid Figure 1 shows the cytopathic inhibitory effect of fuchsic acid.
ＡはＨＩＶ−１とＭＴ−４細胞、ＢはＨＩ Ｖ−２とＭ
Ｔ−４細胞である。A: HIV-1 and MT-4 cells, B: HIV-2 and M
They are T-4 cells.
第２図にＨＩＶ−１の逆転写酵素の抑制効果を示す。FIG. 2 shows the inhibitory effect of HIV-1 reverse transcriptase.
［発明の効果コ
本発明の抗ウィルス剤は、ＡＲＣへの進展、エイズの治
療およびエイズ原因ウィルスの細胞への感染の抑制に有
効である。[Effects of the Invention] The antiviral agent of the present invention is effective in progressing to ARC, treating AIDS, and suppressing infection of cells by the virus that causes AIDS.
また、ＨＩＶ−２への抗ウィルス作用も認められること
より、他のレトロウィルスが原因とされるＡＴＬ （Ａ
ｄｕｌｔ Ｔ ｃｅｌｌ Ｌｅｕｋｅｍｉａ）、Ｈａｉ
ｒ１７ Ｃｅ１ｌ Ｌｅｕｋｅｍｉａなどの造血器腫瘍
にも効果が期待できる。さらに、ＨＢＶ（Ｂ型肝炎）
、ｎｏｎ Ａ ｎｏｎ Ｂ肝炎にも効果がある。In addition, since antiviral effects against HIV-2 have been observed, ATL (ATL), which is thought to be caused by other retroviruses, is
dult T cell Leukemia), Hai
It is also expected to be effective against hematopoietic tumors such as r17 Ce11 Leukemia. Furthermore, HBV (hepatitis B)
It is also effective against non-A and non-B hepatitis.
第１図はフクシン酸の細胞変性阻止効果を示し、■はウ
ィルス感染ＭＴ−４細胞、口はＭＴ−４細胞（コントロ
ール）を示す。また第２図はＨＩＶ−１の逆転写酵素の
抑制効果を示す。FIG. 1 shows the cytopathic inhibitory effect of fuchsic acid, where ■ indicates virus-infected MT-4 cells and the opening indicates MT-4 cells (control). Furthermore, FIG. 2 shows the inhibitory effect on HIV-1 reverse transcriptase.
Claims (1)
に対する抗ウィルス剤。(1) An antiviral agent against the AIDS-causing virus containing fuchsic acid as an active ingredient.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP34012089A JPH02275819A (en) | 1988-12-28 | 1989-12-28 | Antiviral agent on aids virus |
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP63-332327 | 1988-12-28 | ||
| JP33232788 | 1988-12-28 | ||
| JP34012089A JPH02275819A (en) | 1988-12-28 | 1989-12-28 | Antiviral agent on aids virus |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH02275819A true JPH02275819A (en) | 1990-11-09 |
Family
ID=26574155
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP34012089A Pending JPH02275819A (en) | 1988-12-28 | 1989-12-28 | Antiviral agent on aids virus |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH02275819A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2010189314A (en) * | 2009-02-18 | 2010-09-02 | Masami Moriyama | Pernasal administration adjuvant inducing iga antibody |
-
1989
- 1989-12-28 JP JP34012089A patent/JPH02275819A/en active Pending
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2010189314A (en) * | 2009-02-18 | 2010-09-02 | Masami Moriyama | Pernasal administration adjuvant inducing iga antibody |
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