JPH01157993A - Novel platinum (ii) complex and malignant tumor remedy - Google Patents
Novel platinum (ii) complex and malignant tumor remedyInfo
- Publication number
- JPH01157993A JPH01157993A JP62316448A JP31644887A JPH01157993A JP H01157993 A JPH01157993 A JP H01157993A JP 62316448 A JP62316448 A JP 62316448A JP 31644887 A JP31644887 A JP 31644887A JP H01157993 A JPH01157993 A JP H01157993A
- Authority
- JP
- Japan
- Prior art keywords
- present
- complex
- compound
- platinum
- remedy
- 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
- 201000011510 cancer Diseases 0.000 title claims abstract description 8
- HRGDZIGMBDGFTC-UHFFFAOYSA-N platinum(2+) Chemical compound [Pt+2] HRGDZIGMBDGFTC-UHFFFAOYSA-N 0.000 title claims abstract 4
- 239000003814 drug Substances 0.000 claims description 13
- 229940124597 therapeutic agent Drugs 0.000 claims description 8
- 239000004480 active ingredient Substances 0.000 claims description 3
- 239000000126 substance Substances 0.000 claims 2
- 150000001875 compounds Chemical class 0.000 abstract description 19
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 abstract description 17
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 abstract description 5
- 239000000463 material Substances 0.000 abstract 1
- CXLGNJCMPWUZKM-UHFFFAOYSA-N oxane-4-carbaldehyde Chemical compound O=CC1CCOCC1 CXLGNJCMPWUZKM-UHFFFAOYSA-N 0.000 abstract 1
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 25
- 229910052697 platinum Inorganic materials 0.000 description 11
- 241000699670 Mus sp. Species 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- 229940079593 drug Drugs 0.000 description 5
- 230000000259 anti-tumor effect Effects 0.000 description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 206010029155 Nephropathy toxic Diseases 0.000 description 3
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- 230000000694 effects Effects 0.000 description 3
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- 241000699666 Mus <mouse, genus> Species 0.000 description 2
- 206010028980 Neoplasm Diseases 0.000 description 2
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 2
- DVQHYTBCTGYNNN-UHFFFAOYSA-N azane;cyclobutane-1,1-dicarboxylic acid;platinum Chemical compound N.N.[Pt].OC(=O)C1(C(O)=O)CCC1 DVQHYTBCTGYNNN-UHFFFAOYSA-N 0.000 description 2
- 238000000921 elemental analysis Methods 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
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- 150000003057 platinum Chemical class 0.000 description 2
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- 244000215068 Acacia senegal Species 0.000 description 1
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- 229920000945 Amylopectin Polymers 0.000 description 1
- 206010051779 Bone marrow toxicity Diseases 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 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
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- 238000011765 DBA/2 mouse Methods 0.000 description 1
- 239000004278 EU approved seasoning Substances 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- 239000004354 Hydroxyethyl cellulose Substances 0.000 description 1
- 229920000663 Hydroxyethyl cellulose Polymers 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
- 101100498160 Mus musculus Dach1 gene Proteins 0.000 description 1
- 208000002231 Muscle Neoplasms Diseases 0.000 description 1
- 206010033128 Ovarian cancer Diseases 0.000 description 1
- 206010061535 Ovarian neoplasm Diseases 0.000 description 1
- 239000005662 Paraffin oil Substances 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 239000004372 Polyvinyl alcohol Substances 0.000 description 1
- 229920002472 Starch Polymers 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
- 229930006000 Sucrose Natural products 0.000 description 1
- 238000000862 absorption spectrum Methods 0.000 description 1
- 239000000205 acacia gum Substances 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- VJHCJDRQFCCTHL-UHFFFAOYSA-N acetic acid 2,3,4,5,6-pentahydroxyhexanal Chemical compound CC(O)=O.OCC(O)C(O)C(O)C(O)C=O VJHCJDRQFCCTHL-UHFFFAOYSA-N 0.000 description 1
- 231100000215 acute (single dose) toxicity testing Toxicity 0.000 description 1
- 238000011047 acute toxicity test Methods 0.000 description 1
- 230000009876 antimalignant effect Effects 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 238000001479 atomic absorption spectroscopy Methods 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 231100000366 bone marrow toxicity Toxicity 0.000 description 1
- 239000006172 buffering agent Substances 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
- 239000002775 capsule Substances 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- YMHQVDAATAEZLO-UHFFFAOYSA-N cyclohexane-1,1-diamine Chemical compound NC1(N)CCCCC1 YMHQVDAATAEZLO-UHFFFAOYSA-N 0.000 description 1
- 229940127089 cytotoxic agent Drugs 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
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- 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
- 210000004392 genitalia Anatomy 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
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- 235000011187 glycerol Nutrition 0.000 description 1
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007951 isotonicity adjuster Substances 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 150000004682 monohydrates Chemical class 0.000 description 1
- 201000002077 muscle cancer Diseases 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 235000019422 polyvinyl alcohol Nutrition 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
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- 239000007940 sugar coated tablet Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
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- 230000002381 testicular Effects 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 239000004408 titanium dioxide Substances 0.000 description 1
- 235000010215 titanium dioxide Nutrition 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
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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、新規白金■錯体およびそれを有効成分とする
悪性腫瘍治療剤に関する。DETAILED DESCRIPTION OF THE INVENTION <Industrial Application Field> The present invention relates to a novel platinum complex and a therapeutic agent for malignant tumors containing the same as an active ingredient.
〈従来の技術〉
悪性腫瘍の化学療法は、近年シスージアンミンージクロ
ログラチナム■（以下、ＣＤＤＰと略す）の適用で飛躍
的な進歩をとげた。すなわち、ＣＤＤＰは、それまで化
学療法剤での治療が難しかった卵巣癌や精巣筋などの性
器癌に著効を示したためである。しかしながら、ＣＤＤ
Ｐには腎毒性や骨髄毒性などの重篤な副作用があり、臨
床使用上の問題点となっている。<Prior Art> Chemotherapy for malignant tumors has made dramatic progress in recent years with the application of cissudiammine-dichlorogratinum (hereinafter abbreviated as CDDP). That is, this is because CDDP has shown remarkable efficacy against genital cancers such as ovarian cancer and testicular muscle cancer, which were previously difficult to treat with chemotherapeutic agents. However, C.D.D.
P has serious side effects such as nephrotoxicity and bone marrow toxicity, which is a problem in clinical use.
一方、特にＤ Ｌ Ｆ （ｄｏｓｅ ｌｉｎｉｔｉｎｇ
ｆａｃｔｏｒ）となっている腎毒性を改善すべく、様
々な研究が重ねられ、シス−ジアンミン−１，１−シク
ロブタンジ力ルボキシレイトプラチナム■〈以下、ＣＢ
ＤＣＡと略す）、シス−ジアンミン−〇、〇−−グリコ
レイトプラチナム■なとの第二世代白金錯体が開発され
た（特開昭５６−１５４４９３号公報など）。On the other hand, especially D L F (dose lining
In order to improve the nephrotoxicity that has become a factor in
Second-generation platinum complexes such as DCA) and cis-diammine-〇,〇-glycolateplatinum have been developed (Japanese Patent Application Laid-Open No. 154493/1983, etc.).
〈発明が解決しようとする問題点〉
しかしながら、これらの化合物は、腎毒性こそ弱いもの
の、抗腫瘍活性がＣＤＤＰはど高くはない。このため、
抗腫瘍作用が強くかつ、毒性が弱い白金錯体の開発が望
まれている。<Problems to be Solved by the Invention> However, although these compounds have weak nephrotoxicity, their antitumor activity is not as high as that of CDDP. For this reason,
It is desired to develop platinum complexes that have strong antitumor effects and low toxicity.
本発明の目的は、強い抗ｍ瘍活性を有し、かつ毒性が弱
いという両条件を満足する新規白金■錯体を提供するこ
とにあり、さらにかかる両条件を満足する悪性腫瘍治療
剤を提供することにある。The object of the present invention is to provide a novel platinum complex that satisfies both the requirements of having strong anti-malignant activity and low toxicity, and further to provide a therapeutic agent for malignant tumors that satisfies both of these requirements. There is a particular thing.
く問題点を解決するための手段〉 上記目的は、以下の本発明により達成される。Means to solve problems〉 The above object is achieved by the present invention as described below.
すなわち、本発明は、下記式（＾）
で示される新規白金■錯体（以下、本発明化合物と略す
）および上記式（Ａ）で示される新規白金■錯体を有効
成分とする悪性腫瘍治療剤である。That is, the present invention provides a malignant tumor therapeutic agent containing a novel platinum complex represented by the following formula (^) (hereinafter referred to as the compound of the present invention) and a novel platinum complex represented by the above formula (A) as active ingredients. be.
本発明化合物は、３，４−ジヒドロ−２，２−ジメチル
−４−オキソ−２Ｈ−ビラン−６−カルボン酸（Ｂ）と
ジヒドロキソジアミノシクロヘキサン白金■（Ｃ）（以
下、ジアミノシクロヘキサンをｄａｃｈと略す）から合
成することができる。The compound of the present invention comprises 3,4-dihydro-2,2-dimethyl-4-oxo-2H-bilane-6-carboxylic acid (B) and dihydroxodiaminocyclohexane platinum (C) (hereinafter, diaminocyclohexane is referred to as dach). can be synthesized from (omitted).
（Ｃ） （Ｂ）
すなわち、ジヒドロキソｄａｃｈ白金■（Ｃ）の含水エ
タノール溶液と、３，４−ジヒドロ−２゜２−ジメチル
−４−オキソ−２Ｈ−ビラン−６−カルボン酸（Ｂ）を
反応させることにより合成することができる６反応は常
温、常圧下にジヒドロキソｄａｃｈ白金■（Ｃ）と３，
４−ジヒドロ−２，２−ジメチル−４−オキソ−２Ｈ−
ビラン−６−カルボン酸［Ｂ）を含水エタノール溶液中
で混合することにより実施できる。このようにして得ら
れた本発明化合物（八）は、アコ錯体として水を含む場
合があるが、アコ錯体も本発明化合物の範囲に含まれる
。(C) (B) That is, a water-containing ethanol solution of dihydroxodach platinum (C) is reacted with 3,4-dihydro-2゜2-dimethyl-4-oxo-2H-bilane-6-carboxylic acid (B). 6 reactions can be synthesized by combining dihydroxodach platinum (C) and 3,
4-dihydro-2,2-dimethyl-4-oxo-2H-
This can be carried out by mixing bilane-6-carboxylic acid [B) in an aqueous ethanol solution. The compound (8) of the present invention thus obtained may contain water as an aco complex, but the aco complex is also included within the scope of the compound of the present invention.
本発明化合物の原料であるジヒドロキソｄａａｈ白金■
（Ｃ）は、上記式（Ｃ）で示される化合物であり、〔Ｐ
ｔ（トランス−１−ｄａｃｈ）（ＯＨ）２）、（Ｐｔｌ
ランス−ｄ−ｄａｃｈ）（ＯＨ）２）および〔Ｐｔ（シ
ス−ｄａｃｈ）（ＯＨ）２）の三種の異性体が存在する
。Dihydroxo daah platinum, which is the raw material for the compound of the present invention
(C) is a compound represented by the above formula (C), [P
t(trans-1-dach)(OH)2), (Ptl
There are three isomers: lance-d-dach)(OH)2) and [Pt(cis-dach)(OH)2).
ジヒドロキソｄａｃｈ白金■（Ｃ）は次の方法により合
成することができる。Dihydroxodach platinum (C) can be synthesized by the following method.
（Ｄ）
（Ｅ）
＋２ＡｇＣ！
（Ｃ）
本発明化合物の有効量を含む治療剤を臨床において投与
する場合、経口または非経口経路により投与される。そ
の剤形は、錠剤、糖衣錠、火剤、カプセル剤、散剤、ト
ローチ剤、液剤、串刺、注射剤などを包含し、これらは
、医薬上許容される賦形剤（ｅｘｃｉｐｉｅｎｔ ）を
配合して製造される。賦形剤としては次のようなものを
例示することができる。乳糖、ショ糖、ブドウ糖、ソル
ビトール、マンニトール、ばれいしょでんぷん、アミロ
ペクチン、その他各種でんぷん、セルローズ誘導体く例
えば、カルボキシメチルセルローズ、ハイドロキシエチ
ルセルローズなど）、ゼラチン、ステアリン酸マグネシ
ウム、ポリビニルアルコール、ステアリン酸カルシウム
、ポリエチレングリコールワックス、アラビアゴム、タ
ルク、二酸化チタン、オリーブ油、ピーナツ油、ゴマ油
などの植物油、パラフィン油、中性脂肪基剤、エタノー
ル、プロピレングリコール、生理食塩水、滅菌水、グリ
セリン、着色剤、調味剤、濃厚剤、安定剤、等張剤、緩
衝剤などおよびその池医薬上許容される賦形剤。(D) (E) +2AgC! (C) When a therapeutic agent containing an effective amount of the compound of the present invention is administered clinically, it is administered by oral or parenteral route. The dosage forms include tablets, sugar-coated tablets, gunpowders, capsules, powders, lozenges, liquids, skewers, injections, etc., and these are prepared by incorporating pharmaceutically acceptable excipients. be done. Examples of excipients include the following. Lactose, sucrose, glucose, sorbitol, mannitol, potato starch, amylopectin, various other starches, cellulose derivatives (e.g. carboxymethyl cellulose, hydroxyethyl cellulose, etc.), gelatin, magnesium stearate, polyvinyl alcohol, calcium stearate, polyethylene glycol wax , gum arabic, talc, titanium dioxide, vegetable oils such as olive oil, peanut oil, and sesame oil, paraffin oil, neutral fat base, ethanol, propylene glycol, physiological saline, sterile water, glycerin, coloring agents, seasonings, and thickening agents. , stabilizers, isotonic agents, buffering agents and the like and pharmaceutically acceptable excipients.
本発明の治療剤は、本発明化合物をｏ、ｏｏｉ〜８５重
量％、好ましくは０．００５〜６０重量％含有すること
ができる。The therapeutic agent of the present invention may contain o,ooi to 85% by weight, preferably 0.005 to 60% by weight of the compound of the present invention.
本発明の治療剤の投与量は、主として症状により左右さ
れるが、１８成人体重あたり０．００５〜２００■、好
ましくは０．０１〜５０■である。The dosage of the therapeutic agent of the present invention mainly depends on the symptoms, but is 0.005 to 200 cm, preferably 0.01 to 50 cm per 18 adult body weight.
〈実施例〉 以下、実施例により本発明を具体的に説明する。<Example> Hereinafter, the present invention will be specifically explained with reference to Examples.
実施例１
〔Ｐｔ（トランス−ｊ！−ｄａｃｈ）（ＯＨ）２）の含
水エタノール溶液１０．５ＧＩＩ（３，７５ミリモル）
に、３，４−ジヒドロ−２，２−ジメチル−４−オキソ
−２Ｈ−ビラン−６−カルボン酸１．４０ｇのエタノー
ル溶液１０ｍ１を滴下した。室温で一晩撹拌し、析出物
を濾過した。水洗、酢酸エチル洗浄を繰り返したのち、
４０’Ｃで減圧乾燥し、黄色！５）木状のビス（３，４
−ジヒドロ−２゜２−ジメチル−４−オキソ−２Ｈ−ビ
ラン−６−カルポキシラト）（トランス−λ−ｄａｃｈ
）白金■錯体の１水和物（以下、本発明化合物Ａ１と称
する）を１．８０＋ｒ得た。この錯体のＩＲを第１図に
、また、融点と元素分析値を以下に示す（ｐｔは原子吸
光分析により求めた）。Example 1 [Pt(trans-j!-dach)(OH)2] aqueous ethanol solution 10.5 GII (3.75 mmol)
To this, 10 ml of an ethanol solution containing 1.40 g of 3,4-dihydro-2,2-dimethyl-4-oxo-2H-bilane-6-carboxylic acid was added dropwise. Stir overnight at room temperature and filter the precipitate. After repeated washing with water and ethyl acetate,
Dry under reduced pressure at 40'C, yellow! 5) Wooden screws (3, 4
-dihydro-2゜2-dimethyl-4-oxo-2H-bilane-6-carpoxylate) (trans-λ-dach
) 1.80+r of platinum complex monohydrate (hereinafter referred to as the compound A1 of the present invention) was obtained. The IR of this complex is shown in FIG. 1, and the melting point and elemental analysis values are shown below (pt was determined by atomic absorption spectrometry).
融点 ２０８．８〜２１２．２℃
元素分析値（％）（Ｃ２２Ｈ３２Ｎ２０ａ Ｐｔ −Ｈ
２Ｏとして）
実施例２
ＣＤＦ＋マウス（雄性、６週齢、１群６〜１０匹使用）
腹腔内にＤＢＡ／２マウスで継代したマウス白血病細胞
Ｌ１２１０ １０５個を移植した。移植日を０日として
、１８目、５日日、９白目の計３回本発明化合物（Ａ１
）を被検薬として腹腔的投与した。本実験の比較薬とし
てはＣＢＤＣＡ、ＣＤＤＰを用いた。各薬剤は０゜０５
％“Ｔｗｅｅｎ ８０”溶液に溶解または懸濁して使用
した。Ｌ１２１０移植マウスに対する白金錯体の抗腫瘍
作用の効果判定は、以下の式により求められるＴ／ＣＩ
、ならびに３０日０における生存マウス数によって行っ
た。Melting point 208.8~212.2℃ Elemental analysis value (%) (C22H32N20a Pt -H
Example 2 CDF+ mice (male, 6 weeks old, 6-10 mice per group)
105 L1210 mouse leukemia cells passaged in DBA/2 mice were intraperitoneally transplanted. The compound of the present invention (A1
) was administered intraperitoneally as the test drug. CBDCA and CDDP were used as comparative drugs in this experiment. Each drug is 0°05
It was used by dissolving or suspending it in a % Tween 80 solution. The effectiveness of the antitumor effect of the platinum complex on L1210-implanted mice was determined by T/CI determined by the following formula.
, and the number of surviving mice at day 30.
結果を表１に示す。The results are shown in Table 1.
表 １
表１に示す結果から明らかなように、本発明化合物（Ａ
１）は、２５■／ ｋｇ投投与−おいて３４９％のＴ／
Ｃ値を示し、３０日１においての生存マウスも３／６で
あった。これは明らかにＣＤＤＰおよびＣＢＤＣＡより
も強力な抗腫瘍作用であるといえる。Table 1 As is clear from the results shown in Table 1, the compound of the present invention (A
1) is 349% T/kg at 25 kg/kg administration.
C value was shown, and the number of surviving mice on day 30 was also 3/6. This clearly shows a stronger antitumor effect than CDDP and CBDCA.
実施例３
本発明化合物（Ａ１）のマウスにおける急性毒性試験を
ＣＤＤＰを対照として行った。Ｓ（ｃ：ＩｃＲマウス（
雄性；５週齢）の腹腔内に本発明化合物（Ａ１）を被検
薬として投与した。Example 3 An acute toxicity test of the compound (A1) of the present invention in mice was conducted using CDDP as a control. S (c: IcR mouse (
The compound (A1) of the present invention was intraperitoneally administered to a male (5 weeks old) as a test drug.
被検薬は０．０５％“Ｔｗｅｅｎ ８０”溶液に溶解ま
たは懸濁して用いた。投与後１４日口の死亡率からしＤ
５ｏ値を算出した。The test drug was dissolved or suspended in a 0.05% "Tween 80" solution. Mortality rate 14 days after administration Karashi D
The 5o value was calculated.
その結果を表２に示す。The results are shown in Table 2.
表 ２
表２に示す結果から明らかなように、本発明化合物（Ａ
１）はＣＤＤＰに比べ、低毒性である。Table 2 As is clear from the results shown in Table 2, the compound of the present invention (A
1) has lower toxicity than CDDP.
〈発明の効果〉
本発明の化合物は、強い抗Ｓ瘍活性を有し、かつ毒性も
弱く、悪性腫瘍治療剤として有効である。<Effects of the Invention> The compounds of the present invention have strong anti-S tumor activity and low toxicity, and are effective as therapeutic agents for malignant tumors.
第１図は実施例１で得られた本発明化合物（Ａ１）の赤
外吸収スペクトルを示す。FIG. 1 shows the infrared absorption spectrum of the compound (A1) of the present invention obtained in Example 1.
Claims (2)
瘍治療剤。(2) A therapeutic agent for malignant tumors containing a novel platinum (II) complex represented by the following formula (A) ▲Mathematical formulas, chemical formulas, tables, etc.▼...(A) as an active ingredient.
Priority Applications (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP62316448A JPH01157993A (en) | 1987-12-14 | 1987-12-14 | Novel platinum (ii) complex and malignant tumor remedy |
| PCT/JP1988/001137 WO1989004318A1 (en) | 1987-11-11 | 1988-11-11 | Platinum complex and therapeutic agent for malignant tumor |
| EP19880909832 EP0345356A4 (en) | 1987-11-11 | 1988-11-11 | Platinum complex and therapeutic agent for malignant tumor |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP62316448A JPH01157993A (en) | 1987-12-14 | 1987-12-14 | Novel platinum (ii) complex and malignant tumor remedy |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH01157993A true JPH01157993A (en) | 1989-06-21 |
Family
ID=18077201
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP62316448A Pending JPH01157993A (en) | 1987-11-11 | 1987-12-14 | Novel platinum (ii) complex and malignant tumor remedy |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH01157993A (en) |
-
1987
- 1987-12-14 JP JP62316448A patent/JPH01157993A/en active Pending
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