JPH01135718A - Radiation damage treatment drug - Google Patents
Radiation damage treatment drugInfo
- Publication number
- JPH01135718A JPH01135718A JP28964887A JP28964887A JPH01135718A JP H01135718 A JPH01135718 A JP H01135718A JP 28964887 A JP28964887 A JP 28964887A JP 28964887 A JP28964887 A JP 28964887A JP H01135718 A JPH01135718 A JP H01135718A
- Authority
- JP
- Japan
- Prior art keywords
- compound
- radiation
- radiation damage
- disorder
- therapeutic agent
- 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
- 230000005855 radiation Effects 0.000 title claims abstract description 22
- 239000003814 drug Substances 0.000 title claims abstract description 9
- 229940079593 drug Drugs 0.000 title 1
- 229940124597 therapeutic agent Drugs 0.000 claims abstract description 8
- 150000003839 salts Chemical class 0.000 claims abstract description 4
- 230000003449 preventive effect Effects 0.000 claims description 8
- 229940126062 Compound A Drugs 0.000 abstract description 17
- NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 abstract description 17
- 230000000694 effects Effects 0.000 abstract description 7
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 6
- 150000001875 compounds Chemical class 0.000 abstract description 4
- 231100000419 toxicity Toxicity 0.000 abstract description 3
- 230000001988 toxicity Effects 0.000 abstract description 3
- 208000005623 Carcinogenesis Diseases 0.000 abstract description 2
- 208000018522 Gastrointestinal disease Diseases 0.000 abstract description 2
- 230000001154 acute effect Effects 0.000 abstract description 2
- 239000011230 binding agent Substances 0.000 abstract description 2
- 230000036952 cancer formation Effects 0.000 abstract description 2
- 239000002775 capsule Substances 0.000 abstract description 2
- 231100000504 carcinogenesis Toxicity 0.000 abstract description 2
- 230000001684 chronic effect Effects 0.000 abstract description 2
- 230000004064 dysfunction Effects 0.000 abstract description 2
- 239000008187 granular material Substances 0.000 abstract description 2
- 230000003394 haemopoietic effect Effects 0.000 abstract description 2
- 238000002347 injection Methods 0.000 abstract description 2
- 239000007924 injection Substances 0.000 abstract description 2
- 239000000546 pharmaceutical excipient Substances 0.000 abstract description 2
- 239000000843 powder Substances 0.000 abstract description 2
- 239000006188 syrup Substances 0.000 abstract description 2
- 235000020357 syrup Nutrition 0.000 abstract description 2
- 239000003826 tablet Substances 0.000 abstract description 2
- DYEFUKCXAQOFHX-UHFFFAOYSA-N Ebselen Chemical compound [se]1C2=CC=CC=C2C(=O)N1C1=CC=CC=C1 DYEFUKCXAQOFHX-UHFFFAOYSA-N 0.000 abstract 1
- 230000002411 adverse Effects 0.000 abstract 1
- 208000035475 disorder Diseases 0.000 abstract 1
- 230000036737 immune function Effects 0.000 abstract 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 4
- 241000699670 Mus sp. Species 0.000 description 4
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 4
- 239000001768 carboxy methyl cellulose Substances 0.000 description 3
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 241000700159 Rattus Species 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 108010024636 Glutathione Proteins 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- UFULAYFCSOUIOV-UHFFFAOYSA-N cysteamine Chemical class NCCS UFULAYFCSOUIOV-UHFFFAOYSA-N 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000000779 depleting effect Effects 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 229960003180 glutathione Drugs 0.000 description 1
- 208000026278 immune system disease Diseases 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
Landscapes
- 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、２−フェニル−１，２−ベンゾイソセレナゾ
ール−３（２Ｈ）−オン（以下、化合物Ａと称す）又は
その生理学的許容塩を含有する放射線障害の予防及び治
療剤に関する。Detailed Description of the Invention <Industrial Application Fields> The present invention relates to 2-phenyl-1,2-benziisoselenazol-3(2H)-one (hereinafter referred to as compound A) or its physiologically tolerable compound. The present invention relates to a preventive and therapeutic agent for radiation damage containing a salt.
〈従来の技術）
放射線障害の予防に関しては、放射線の被曝を避ける消
極的方法が基本である。そして、実験的には生体内の酸
素を欠乏させると放射線障害が予防されることが知られ
ている。しかし、このような方法は実際には用いること
が出来ない。(Prior Art) Regarding the prevention of radiation damage, passive methods of avoiding radiation exposure are fundamental. It has been experimentally known that depleting the body of oxygen can prevent radiation damage. However, such a method cannot be used in practice.
又、システアミン訪導体のなかには放射線障害の予防作
用を示す誘導体がある。しかしながら、これらの化合物
は毒性面で十分満足できるものではない、従って、放射
線障害については、治療効果に優れ且つ安全性の高い薬
剤の開発が望まれている。Further, among the cysteamine derivatives, there are derivatives that exhibit preventive effects against radiation damage. However, these compounds are not fully satisfactory in terms of toxicity.Therefore, there is a desire for the development of highly safe and highly effective therapeutic agents for radiation damage.
又、化合物Ａが有する作用としてはグルタチオンペルオ
キシダーゼ様抗酸化作用および抗炎症作用が知られてい
る（バイオケミカル ）１−マコロジーＶｏ１．３３
Ｎｏ、２０３２３５−３２３９． ３２４１−３２４５
（１９８４））、シかしながら、これらの作用は放射線
障害の予防および治療に直接結びつ（ものではない。In addition, Compound A is known to have glutathione peroxidase-like antioxidant action and anti-inflammatory action (Biochemical) 1-Macology Vol. 1.33
No, 203235-3239. 3241-3245
(1984)), but these effects are not directly linked to the prevention and treatment of radiation damage.
〈発明が解決しようとする問題点〉
本発明者らは、新規な放射線障害の予防及び治療剤を開
発すべく鋭意検討した結果、化合物Ａが優れた放射線障
害の予防及び治療効果を有することを見い出し、本発明
を完成した。<Problems to be Solved by the Invention> As a result of intensive studies aimed at developing a novel preventive and therapeutic agent for radiation damage, the present inventors have found that Compound A has excellent preventive and therapeutic effects on radiation damage. Heading, the invention was completed.
（発明の構成〉
本発明は、化合物Ａ又はその生理学的許容塩を含有する
放射線障害の予防及び治療剤に関するものである。(Structure of the Invention) The present invention relates to a preventive and therapeutic agent for radiation damage containing Compound A or a physiologically acceptable salt thereof.
本発明にかかわる放射線障害としては急性原爆症および
慢性原爆症等をあげることができ、該障害の具体例とし
ては放射線障害にかかわる消化管障害、造血機能障害、
免疫機能障害、発癌等をあげることができる。Radiation damage related to the present invention includes acute atomic bomb disease and chronic atomic bomb disease, and specific examples of such damage include gastrointestinal disorders related to radiation damage, hematopoietic dysfunction,
Examples include immune dysfunction and carcinogenesis.
本発明の医薬にかかわる製剤としては、錠剤、カプセル
剤、散剤、顆粒剤、シロップ剤、注射剤等をあげること
ができ、これらの製剤は化合物Ａに賦形剤、結合剤、崩
壊剤、溶解剤等の添加剤を組み合わせて公知の製剤技術
を用いることにより製造することができる。製剤の具体
的処方例を以下に示す。Preparations related to the pharmaceutical of the present invention include tablets, capsules, powders, granules, syrups, injections, etc., and these preparations include Compound A, excipients, binders, disintegrants, and dissolving agents. It can be manufactured by combining additives such as agents and using known formulation techniques. Specific formulation examples of the preparation are shown below.
錠剤：
化合物Ａ ５０ ｍｇカルボキシ
メチルセルロース ２５ ｍｇでんぷん
５ ｍｇ結晶セルロース ４０
ｍｇステアリン酸マグネシウム ２ ｍｇ計
１２２ ｍｇ化合物Ａ
は通常経口又は非経口投与され、その投与量は、経口投
与の場合成人１人当たり １００〜２０００ｍｇ／日、
好ましくは２００〜１０００ｍｇ／日の範囲であり、患
者の症状に応じて適宜増減すればよい。Tablet: Compound A 50 mg carboxymethyl cellulose 25 mg starch
5 mg crystalline cellulose 40
mg magnesium stearate 2 mg meter
122 mg Compound A
is usually administered orally or parenterally, and the dosage is 100 to 2000 mg/day per adult for oral administration.
It is preferably in the range of 200 to 1000 mg/day, and may be increased or decreased as appropriate depending on the patient's symptoms.
化合物Ａの毒性は、マウスおよびラットに経口又は腹腔
内投与で検討した結果、下記のＬＤｇｏ （ｍｇ／ｋｇ
）値で示されているように極めて低毒性のものであり、
又高用量投与時の所見についても副作用的に問題となる
ものはなんら認められなかった。The toxicity of Compound A was investigated by oral or intraperitoneal administration to mice and rats.
) has extremely low toxicity as shown by the value.
Also, no problematic side effects were observed during high-dose administration.
表１ 急性毒性
動物種 投与経路 ＬＤ５０ （ｍｇ／ｋｇ）
マウス ｐ、ｏ、 ＞ ６８１０ｉ、
ｐ、 ７４０
ラット ｐ、ｏ、 ＞ ８８１０ｉ、
ｐ、 ５８０
〈発明の効果〉
化合物Ａは放射線照射モデルにおけるマウスの死亡率を
有意に抑制した。従って、化合物Ａは放射線障害の予防
及び治療剤として優れ且つ安全性の高い化合物である。Table 1 Acutely toxic animal species Administration route LD50 (mg/kg)
Mouse p, o, > 6810i,
p, 740 rat p, o, > 8810i,
p, 580 <Effects of the Invention> Compound A significantly suppressed the mortality rate of mice in the radiation irradiation model. Therefore, Compound A is an excellent and highly safe compound as a preventive and therapeutic agent for radiation damage.
以下、本発明を更に実施例により説明するが、本発明は
これに限定されるものではない。EXAMPLES Hereinafter, the present invention will be further explained with reference to Examples, but the present invention is not limited thereto.
実施例
射線照射に伴なう死亡率に対する化合物Ａの処呈
雌性ＢＤＦ、マウス（日本チャールスリバー社、８週令
）に化合物Ａの０．銚カルボキシメチルセルロース懸濁
液を３Ｏｎ＋ｇ／ｋｇまたは３ｏｏｍｇ／ｋｇの投与量
で経口ゾンデを用い２４時間間隔で２回強制的に経口投
与した。対照群には０．５＊カルボキシメチルセルロー
ス液（以下、０．５ＸＣＭＣ）のみを強制的に経口投与
した。２回目の投与直後に６０ＯＲのＸ線をマウスに照
射し、以後毎日生死を判定した。試験は１群６匹で行な
った。結果を表−１に示した。Example Treatment of Compound A on Mortality Associated with Radiation Irradiation Female BDF mice (Japan Charles River Co., Ltd., 8 weeks old) were treated with Compound A at 0.5%. The carboxymethylcellulose suspension was forcibly administered twice at 24-hour intervals using an oral probe at a dose of 3On+g/kg or 3oomg/kg. To the control group, only 0.5*carboxymethylcellulose solution (hereinafter referred to as 0.5XCMC) was forcibly administered orally. Immediately after the second administration, the mice were irradiated with 60OR X-rays, and thereafter, survival or death was determined every day. The test was conducted with 6 animals per group. The results are shown in Table-1.
表−１
＊：Ｘ線照射１２日及び１８日自復の０．５Ｘ ＣＭＣ
投与群と化合物Ａ ３００ｍｇ／ｋｇ投与群とにおいて
、Ｆｉｓｃｈｅｒの直接検定法を用い検定した結果、６
＊の危険率で有意差を認めた。Table-1 *: 0.5X CMC after 12 days of X-ray irradiation and 18 days of recovery
As a result of testing using Fischer's direct test method in the administration group and the compound A 300 mg/kg administration group, 6
*A significant difference was observed in the risk rate.
上記の結果から明らかなように対照群（０，５９６ＣＭ
Ｇ投与群）では１２日自社全匹死亡したが３００ｍｇ／
ｋｇ投与した群では６匹中４匹生存していた。従って、
化合物Ａが優れた放射線防護効果、即ち、放射線障害、
の予防及び治療効果を有することが確認された。As is clear from the above results, the control group (0,596CM
G administration group), all the animals died on the 12th, but 300mg/
In the group administered with 4 kg, 4 out of 6 animals survived. Therefore,
Compound A has an excellent radiation protection effect, that is, radiation damage,
It was confirmed that it has preventive and therapeutic effects.
Claims (1)
３（２Ｈ）−オンまたはその生理学的許容塩を含有する
放射線障害の予防および治療剤1,2-phenyl-1,2-benzisoselenazole-
Preventive and therapeutic agent for radiation damage containing 3(2H)-one or a physiologically acceptable salt thereof
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP28964887A JPH01135718A (en) | 1987-11-18 | 1987-11-18 | Radiation damage treatment drug |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP28964887A JPH01135718A (en) | 1987-11-18 | 1987-11-18 | Radiation damage treatment drug |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH01135718A true JPH01135718A (en) | 1989-05-29 |
Family
ID=17745958
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP28964887A Pending JPH01135718A (en) | 1987-11-18 | 1987-11-18 | Radiation damage treatment drug |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH01135718A (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1996033712A1 (en) * | 1995-04-25 | 1996-10-31 | Daiichi Pharmaceutical Co., Ltd. | Remedy for acquired immunodeficiency syndrome |
| US7671211B1 (en) | 1999-03-31 | 2010-03-02 | Arne Holmgren | Substrates for thioredoxin reductase |
| US10058542B1 (en) | 2014-09-12 | 2018-08-28 | Thioredoxin Systems Ab | Composition comprising selenazol or thiazolone derivatives and silver and method of treatment therewith |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5632422A (en) * | 1979-08-27 | 1981-04-01 | Mochida Pharmaceut Co Ltd | Preventive and remedy for disorder caused by active oxygen in living body |
| JPS6150693A (en) * | 1984-08-14 | 1986-03-12 | Kawasaki Steel Corp | Treatment of waste water at time of preparation of purified coke oven gas |
-
1987
- 1987-11-18 JP JP28964887A patent/JPH01135718A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5632422A (en) * | 1979-08-27 | 1981-04-01 | Mochida Pharmaceut Co Ltd | Preventive and remedy for disorder caused by active oxygen in living body |
| JPS6150693A (en) * | 1984-08-14 | 1986-03-12 | Kawasaki Steel Corp | Treatment of waste water at time of preparation of purified coke oven gas |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1996033712A1 (en) * | 1995-04-25 | 1996-10-31 | Daiichi Pharmaceutical Co., Ltd. | Remedy for acquired immunodeficiency syndrome |
| US7671211B1 (en) | 1999-03-31 | 2010-03-02 | Arne Holmgren | Substrates for thioredoxin reductase |
| US10058542B1 (en) | 2014-09-12 | 2018-08-28 | Thioredoxin Systems Ab | Composition comprising selenazol or thiazolone derivatives and silver and method of treatment therewith |
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