JPH07101972A - Anti-tumor agent and its production - Google Patents
Anti-tumor agent and its productionInfo
- Publication number
- JPH07101972A JPH07101972A JP27133193A JP27133193A JPH07101972A JP H07101972 A JPH07101972 A JP H07101972A JP 27133193 A JP27133193 A JP 27133193A JP 27133193 A JP27133193 A JP 27133193A JP H07101972 A JPH07101972 A JP H07101972A
- Authority
- JP
- Japan
- Prior art keywords
- salt
- formula
- cisplatin
- action
- chloroosmosenium
- 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.)
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- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
Description
【0001】[0001]
【産業上の利用分野】本発明は新規な抗腫瘍剤とその製
造方法に関する。TECHNICAL FIELD The present invention relates to a novel antitumor agent and a method for producing the same.
【0002】[0002]
【従来の技術】癌の化学療法剤としてアルキル化剤、核
酸代謝結抗剤、抗生物質及び植物アルカロイド等が用い
られており、さらに年々多数の新規抗腫瘍剤が開発され
ている。しかし、ごく一部の癌種を除いて化学療法のみ
で、完全治癒できる例は非常に少なく、一層優れた抗腫
瘍剤の出現が待望されている。従来の抗癌剤の中でもシ
スプラチン(シス−ジクロロアミンプラチナム)に代表
される白金錯体は他の薬剤が有効な効果を示さない固形
癌に卓効を示す場合があることから、白金その他の金属
元素含有化合物を対象に、抗腫瘍剤が盛んに探索されて
いる。しかし、シスプラチンをしのぐ化合物はまだ見い
出されていない。一方シスプラチン耐性細胞の出現も問
題となっている。シスプラチンの作用機作は細胞核内D
NAの修飾と考えられているが、シスプラチンを補完
し、さらに、シスプラチン耐性細胞にダメージを与える
観点からは、シスプラチンとは作用機作の異なる含金属
抗腫瘍剤の開発が重要である。下記式(II)で示される
フェロセニウム塩は細胞内の電子伝達系に影響を与える
ことが知られ(Carneyら、J. Am. Chem. Soc., 1
06, 2565 (1984) )細胞レベルでの生育抑制(Koep
fら、J. Cancer Res. Clin. Oncol., 108, 336 (198
4))と抗腫瘍剤としての有効性が明らかになっている
(Koepfら、DE3404443A1)。特に、シ
スプラチンとの同時投与における相乗効果は注目されて
いる(Neuseら、Appl. Organomet. Chem., 4, 19
(1990))。式(II)2. Description of the Related Art Alkylating agents, nucleic acid metabolism-inhibiting agents, antibiotics, plant alkaloids and the like are used as chemotherapeutic agents for cancer, and many new antitumor agents are being developed year by year. However, there are very few cases where a complete cure can be achieved with only chemotherapy except for a few cancer types, and the appearance of a better antitumor agent is desired. Among conventional anticancer agents, platinum complexes represented by cisplatin (cis-dichloroamineplatinum) may be effective for solid tumors in which other agents do not show effective effects, and thus platinum and other metal element-containing compounds. Antitumor agents are being actively searched for. However, no compound has been found that outperforms cisplatin. On the other hand, the appearance of cisplatin-resistant cells is also a problem. The mechanism of action of cisplatin is intracellular D
It is considered to be a modification of NA, but from the viewpoint of complementing cisplatin and damaging cisplatin-resistant cells, it is important to develop a metal-containing antitumor agent having a different mechanism of action from cisplatin. It is known that the ferrocenium salt represented by the following formula (II) affects the electron transport system in cells (Carney et al., J. Am. Chem. Soc., 1
06 , 2565 (1984)) Growth suppression at cell level (Koep
f et al., J. Cancer Res. Clin. Oncol., 108 , 336 (198
4)) and its effectiveness as an antitumor agent has been revealed (Koepf et al., DE 3404443A1). In particular, synergistic effects in co-administration with cisplatin have been noted (Neuse et al., Appl. Organomet. Chem., 4 , 19).
(1990)). Formula (II)
【0003】[0003]
【化2】 [Chemical 2]
【0004】(式中、X- はヘキサフルオロホスフェー
トイオン(PF6 -)、テトラフルオロボレートイオン、
ピクリン酸イオン、テトラクロロフェレートイオンなど
のアニオンである。)[0004] (wherein, X - is hexafluorophosphate ion (PF 6 -), tetrafluoroborate ion,
Anions such as picrate and tetrachloroferrate. )
【0005】[0005]
【発明が解決しようとする課題】しかしながら、このフ
ェロセニウム塩の効力も実際の治療上満足できるもので
はない。またその水溶液は中性において不安定で徐々に
分解し沈殿を生じるという欠点がある。よって、フェロ
セニウム塩と同種の作用機構が期待され、しかもこれよ
りさらに強力な癌細胞増殖抑制作用を有し、水溶液中で
安定な抗腫瘍剤の開発が待望されている。However, the efficacy of this ferrocenium salt is not satisfactory in actual treatment. Further, the aqueous solution is unstable at neutral and gradually decomposes to form a precipitate. Therefore, an action mechanism similar to that of ferrocenium salt is expected, and further, development of an antitumor agent which has a stronger cancer cell growth inhibitory action and is stable in an aqueous solution is desired.
【0006】[0006]
【課題を解決するするための手段】本発明者らは、この
ような従来の有機金属制癌剤の難点を克服するため、多
数のOs含有メタロセニウム塩を合成し試験した。その
結果、下記式(III)The present inventors have synthesized and tested a large number of Os-containing metallocenium salts in order to overcome the drawbacks of such conventional organometallic anticancer agents. As a result, the following formula (III)
【0007】[0007]
【化3】 [Chemical 3]
【0008】で示されるオスモセニウム塩そのものの癌
細胞抑制作用は微弱だったが、クロロオスモセニウム塩
としたものが水溶液からの再結晶により精製物として得
られ、それが極めて強力な癌細胞増殖抑制作用を示すこ
とを見い出し、この知見に基づき本発明をなすに至っ
た。すなわち本発明は (1)下記式(I)で表わされるクロロオスモセニウム
塩を有効成分として含有することを特徴とする抗腫瘍
剤、[0008] Although the osmosenium salt itself showed a weak inhibitory effect on cancer cells, a chloroosmosenium salt was obtained as a purified product by recrystallization from an aqueous solution, which is a very strong inhibitory agent for cancer cell growth. Based on this finding, the present invention has been completed. That is, the present invention provides: (1) an antitumor agent comprising a chloroosmosenium salt represented by the following formula (I) as an active ingredient,
【0009】[0009]
【化4】 [Chemical 4]
【0010】(式中、Yはアニオンを示す。) (2)Yのアニオンがヘキサフルオロホスフェートイオ
ン(PF6 -)、テトラフルオロボレートイオン、ピクリ
ン酸イオンであることを特徴とする(1)項記載の抗腫
瘍剤、 (3)粗クロロオスモセニウム塩の飽和水溶液を調製
し、これから再結晶により、式(I)で表わされる
(1)項記載の精製クロロオスモセニウム塩を得ること
を特徴とする抗腫瘍剤の製造方法を提供するものであ
る。[0010] (wherein, Y represents an anion.) (2) Y anions hexafluorophosphate ion (PF 6 -), tetrafluoroborate ion, characterized in that it is a picrate ion (1) term (3) A saturated aqueous solution of a crude chloroosmosenium salt is prepared and recrystallized from this to obtain a purified chloroosmosenium salt represented by the formula (I) according to item (1). The present invention provides a method for producing a characteristic antitumor agent.
【0011】本発明に用いられる上記式(I)で表わさ
れるクロロオスモセニウムカチオンに対するアニオンと
しては該カチオンを中和するに十分なアニオンで薬物学
的に許容できるものであれば特に制限はなく、上記のヘ
キサフルオロホスフェートイオンの他、テトラフルオロ
ボレートイオンやピクラートイオン等が用いられる。な
お、アンモニウムヘキサフルオロホスフェートやナトリ
ウムテトラフルオロボレートなどには本発明の式(I)
の化合物が適用される濃度範囲ではほとんど制癌活性の
ないことは確認され、本発明における癌細胞増殖抑制作
用はクロロオスモセニウムカチオンによるものと考えら
れる。The anion for the chloroosmosenium cation represented by the above formula (I) used in the present invention is not particularly limited as long as it is an anion sufficient to neutralize the cation and is pharmaceutically acceptable. In addition to the above hexafluorophosphate ion, tetrafluoroborate ion, picrate ion and the like are used. In addition, ammonium hexafluorophosphate, sodium tetrafluoroborate and the like are represented by the formula (I) of the present invention.
It was confirmed that the compound has almost no antitumor activity in the concentration range applied, and the cancer cell growth inhibitory action in the present invention is considered to be due to the chloroosmosenium cation.
【0012】本発明に係る化合物は市販のオスモセンを
塩酸の存在下に塩化第2鉄で酸化し、適当なアニオンの
塩を加えて沈殿させて合成することができる。従来オス
モセニウム塩の製造方法自体は公知である(Smith
ら、Inorg. Chem., 26, 2882(1987) )が、再結晶精製
のために有機溶媒を用いており生成物の構造は従来明ら
かではなく、本発明に係るクロロオスモセニウム塩の製
造方法は知られていない。本発明の製造方法においては
再結晶溶媒として、水を用いることを特徴とする。本発
明に係る式(I)で表わされるクロロオスモセニウム塩
の合成反応は次式で表わすことができる。The compound of the present invention can be synthesized by oxidizing commercially available osmosene with ferric chloride in the presence of hydrochloric acid, and adding a salt of a suitable anion to precipitate the compound. Conventionally, the manufacturing method itself of an osmosenium salt is known (Smith
Et al., Inorg. Chem., 26 , 2882 (1987)) uses an organic solvent for purification by recrystallization, and the structure of the product has not been clarified hitherto, and a method for producing a chloroosmosenium salt according to the present invention is disclosed. Is not known. The production method of the present invention is characterized in that water is used as a recrystallization solvent. The synthetic reaction of the chloroosmosenium salt represented by the formula (I) according to the present invention can be represented by the following formula.
【0013】[0013]
【化5】 [Chemical 5]
【0014】酸化剤は塩化第2鉄に制限されず、塩酸が
存在すれば鉄ミョウバン(FeNH4(SO4)2 ・12H
2 O)を用いてもよい。生成したオスモセニウム塩は粗
生成物として沈殿するが、本発明ではこれを通常、温度
40〜60℃においてその温度における飽和濃度(5mg
/ml 〜10mg/ml )になるように溶解させ、不溶分を濾
別後、濾液を4〜10℃に冷却放置することにより結晶
として精製クロロオスモセニウム塩として得ることがで
きる。本発明方法では水を溶媒として用いることによ
り、高純度の結晶が得られ、安価で安全であるという作
用効果を奏する。The oxidant is not limited to ferric chloride, but if hydrochloric acid is present, iron alum (FeNH 4 (SO 4 ) 2 .12H
2 O) may be used. The osmosenium salt formed precipitates as a crude product, which is usually used in the present invention at a saturated concentration (5 mg) at a temperature of 40 to 60 ° C.
/ ml to 10 mg / ml), the insoluble matter is filtered off, and the filtrate is left to cool to 4 to 10 ° C to obtain purified chloroosmosenium salt as crystals. In the method of the present invention, by using water as a solvent, high-purity crystals can be obtained, which is advantageous in that they are inexpensive and safe.
【0015】上記式(I)で表わされる化合物は優れた
抗腫瘍作用を示す。例えば、このクロロオスモセニウム
ヘキサフルオロホスフェート(式(I)中Y- はP
F6 -)は後述の実験例で示すごとく、各種の癌細胞の増
殖を強力に抑制する。この活性をIC50で比較すると、
いずれの細胞に対しても式(I)の化合物はフェロセニ
ウム塩(式(II)、ただしX- はPF6 -)よりも小さい
値を示し、より強力であるが、とりわけヒト癌細胞のU
937やCOLO320に対しては3〜5倍強力であ
る。さらに、シスプラチンと同時投与すると、それ単独
では効果の低い0.3μMのシスプラチンの制癌作用を
飛躍的に高めるという効果もある。このように、強力な
制癌作用を持つ上に、水溶液は室温で数十時間安定であ
り、フェロセニウム塩(式(II))のように次第に沈殿
を生じることもない。The compound represented by the above formula (I) exhibits an excellent antitumor action. For example, this chloroosmosenium hexafluorophosphate (Y − in the formula (I) is P
F 6 -) is as shown in the experimental examples described later, strongly inhibits the growth of a variety of cancer cells. Comparing this activity by IC 50 ,
In any cell, the compound of formula (I) shows a smaller value than the ferrocenium salt (formula (II), where X − is PF 6 − ), and is more potent, but especially U of human cancer cells.
It is 3 to 5 times stronger than 937 and COLO320. Furthermore, when co-administered with cisplatin, it has the effect of dramatically increasing the carcinostatic effect of 0.3 μM cisplatin, which is not effective by itself. Thus, in addition to having a strong anti-cancer effect, the aqueous solution is stable at room temperature for several tens of hours, and does not cause gradual precipitation unlike the ferrocenium salt (formula (II)).
【0016】式(I)で示される化合物は他の抗腫瘍剤
例えばシスプラチンから類推して任意慣用の方法で投与
用に調製することができる。従って、この発明は人体用
医薬として好適な少なくとも一種の式(I)で表わされ
る化合物又はその製剤組成物をも含有するものである。
このような組成物は任意所要の製薬用担体あるいは賦形
剤により慣用の方法で使用に供される。The compounds of formula (I) may be prepared for administration in any conventional manner by analogy with other antitumor agents such as cisplatin. Therefore, the present invention also comprises at least one compound represented by the formula (I) or a pharmaceutical composition thereof, which is suitable as a medicine for human body.
Such a composition is provided for use in a conventional manner with any required pharmaceutical carrier or excipient.
【0017】[0017]
【作用】作用機作を検討するために、酸素電極を用い培
養液中の溶存酸素の細胞による消費速度を測定した。式
(I)に包含される化合物(1)(Y- はPF6 -)の存
在下では、このO2 消費速度はコントロールに比べて4
7%に低下していた。一方、重水溶液中でアデノシンや
グアノシンと化合物(1)を混合しNMRスペクトルを
測定したが、これら核酸塩基への配位はほとんど認めら
れなかった。したがって、癌細胞増殖抑制作用は呼吸阻
害に基づくものではないかと推測されるが、この点は核
酸への結合によるシスプラチンの作用機構と異なってい
る。[Function] In order to study the mechanism of action, the consumption rate of dissolved oxygen by cells in the culture medium was measured using an oxygen electrode. In the presence of the compound (1) included in the formula (I) (Y − is PF 6 − ), the O 2 consumption rate is 4% as compared with the control.
It had dropped to 7%. On the other hand, the compound (1) was mixed with adenosine or guanosine in a heavy aqueous solution and the NMR spectrum was measured, but the coordination to these nucleic acid bases was hardly observed. Therefore, it is speculated that the cancer cell growth inhibitory action is based on respiratory inhibition, which is different from the mechanism of action of cisplatin by binding to nucleic acid.
【0018】[0018]
【実施例】次に本発明を実施例に基づきさらに詳細に説
明する。 実施例1 市販のオスモセン966mgをベンゼン70mlに溶か
し、これに4N塩酸の42mlと5.74gの塩化第2
鉄(6水和物)を加え室温で24時間激しく撹拌した。
水35mlを加え不溶分を溶解させた後、ベンゼン層を
取り除いた。ついで、水層をベンゼン50mlずつで2
回洗浄した。この水層を氷冷し、アンモニウムヘキサフ
ルオロホスフェート2.33gを含む水5mlを加え、
よく撹拌し、12時間4℃に放置した。沈殿物をろ取
し、少量の冷水で洗浄後、減圧乾燥して1.474gの
微赤色粉末を得た(収率98%)。この粗生成物1.2
gを50℃の水192mlに溶かし不溶分をろ別後、氷
冷し、式(I)の化合物(1)(Y- はPF6 -)の赤色
針状品を1.1g得た(オスモセンからの収率89
%)。分解点180℃以上。元素分析値:炭素、24.
03%;水素、2.07%;塩素、6.96%(分子式
C10H10ClOsPF6 に対する計算値は炭素23.9
8%、水素2.01%、塩素7.08%である)。この
結晶についてX線結晶解析を行い、構造を決定したとこ
ろ、その結晶学的データは以下の通りであった。 結晶形:3斜晶 格子定数:a=6.589、b=9.417、c=1
0.382Å α=84.71、β=88.30、γ=87.71° Z=2、V=640.7Å3 The present invention will be described in more detail based on the following examples. Example 1 966 mg of commercially available osmosene was dissolved in 70 ml of benzene, and 42 ml of 4N hydrochloric acid and 5.74 g of second chloride were dissolved in this solution.
Iron (hexahydrate) was added, and the mixture was vigorously stirred at room temperature for 24 hours.
After adding 35 ml of water to dissolve the insoluble matter, the benzene layer was removed. Then, the water layer is added with 50 ml of benzene for 2 times.
Washed twice. This water layer was ice-cooled, 5 ml of water containing 2.33 g of ammonium hexafluorophosphate was added,
Stir well and let stand at 4 ° C. for 12 hours. The precipitate was collected by filtration, washed with a small amount of cold water, and dried under reduced pressure to obtain 1.474 g of a slightly reddish powder (yield 98%). This crude product 1.2
g was dissolved in 192 ml of water at 50 ° C., the insoluble matter was filtered off, and the mixture was ice-cooled to obtain 1.1 g of a red needle-shaped product of the compound (1) of formula (I) (Y − is PF 6 − ). Yield from 89
%). Decomposition point 180 ° C or higher. Elemental analysis value: carbon, 24.
03%; hydrogen, 2.07%; chlorine, 6.96% (calculated value for molecular formula C 10 H 10 ClOsPF 6 is carbon 23.9.
8%, 2.01% hydrogen, 7.08% chlorine). This crystal was subjected to X-ray crystallography to determine its structure, and its crystallographic data were as follows. Crystal form: triclinic Lattice constant: a = 6.589, b = 9.417, c = 1
0.382Å α = 84.71, β = 88.30, γ = 87.71 ° Z = 2, V = 640.7Å 3
【0019】実施例2 S180マウス肉腫細胞、U937ヒト組織球性リンパ
腫細胞、HL60ヒト前骨髄性白血病細胞及びColo
320ヒト結腸腺癌細胞を5%牛胎仔血清を含むMEM
培地(S180)または10%牛胎仔血清を含むRPM
I1640培地(U937、HL60、Colo32
0)に1.07×105 個/mlの割合で懸濁し、24
ウェルマルチプレートの各ウェルに1.4mlずつ分注
した。実施例1で得た化合物(1)を1.5mM、0.
45mM、0.15mM、0.045mMまたは0.0
15mMの濃度で含む水溶液0.1mlもしくは純水の
0.1mlを各ウェルに添加し、37℃のCO2 インキ
ュベータ中で72時間培養後、細胞数をコールターカウ
ンターで計測した。細胞数対サンプル濃度の曲線からコ
ントロールの細胞数の50%になるよう増殖を抑制する
サンプル濃度(IC50 、μM)を求めた。結果を表1に
まとめた。参考のためにフェロセニウム塩(式(II)の
化合物、ただしX- はPF6 -)とオスモセニウム塩(式
(III)の化合物)についての結果も示した。この表から
明らかなように、式(I)の化合物(1)(式(I)、
ただしY-はPF6 -)はいずれの細胞に対してもフェロ
セニウム塩(式(II)、ただしX-はPF6 -)やオスモ
セニウム塩(式(III))より小さなIC50を示し、した
がって、より強力な癌細胞増殖抑制作用を持つことがわ
かる。また、急性毒性試験によれば、化合物(1)の、
マウスの半致死量は、50mg/kg 又はそれ以下であっ
た。Example 2 S180 mouse sarcoma cells, U937 human histiocytic lymph
Tumor cells, HL60 human promyelocytic leukemia cells and Colo
320 MEM containing 5% fetal bovine serum containing human colon adenocarcinoma cells
RPM containing medium (S180) or 10% fetal bovine serum
I1640 medium (U937, HL60, Colo32
0) to 1.07 × 10Five Suspended at a rate of 24 cells / ml, 24
Dispense 1.4 ml to each well of the well multiplate
did. Compound (1) obtained in Example 1 was added at 1.5 mM, 0.1 mM.
45 mM, 0.15 mM, 0.045 mM or 0.0
0.1 ml of aqueous solution containing 15 mM concentration or pure water
Add 0.1 ml to each well and CO at 37 ℃2 ink
After culturing for 72 hours in an incubator, count the number of cells by Coulter Cow
Measured. From the curve of cell number vs. sample concentration
Inhibits proliferation to 50% of control cell number
Sample concentration (IC50 , ΜM) was determined. The results are shown in Table 1.
Summarized. For reference, the ferrocenium salt (of formula (II)
Compound, but X- Is PF6 -) And osmosenium salt (formula
The results for (III) compounds are also shown. From this table
As is apparent, compound (1) of formula (I) (formula (I),
However, Y-Is PF6 -) Is a ferro for all cells
Cenium salt (formula (II), where X-Is PF6 -) Or Osmo
IC smaller than selenium salt (formula (III))50Showed and did
Therefore, it has a stronger cancer cell growth inhibitory effect.
Light In addition, according to the acute toxicity test,
The semi-lethal dose in mice is 50 mg / kg or less.
It was
【0020】[0020]
【表1】 [Table 1]
【0021】実施例3 シスプラチン0.3μMまたは1.0μMと式(I)の
化合物(1)(式(I)中Y- はPF6 -)15μMの同
時投与における細胞増殖抑制率を前記と同様に試験し
た。コントロールはシスプラチンも化合物(1)も投与
していない場合であり、表2ではこの時の細胞数を10
0で表わしてある。この表から、本発明の化合物(1)
はシスプラチンの癌細胞増殖抑制作用を2倍〜3培強に
増殖する効果のあることがわかる。Example 3 The cell growth inhibitory rate when coadministration of 0.3 μM or 1.0 μM of cisplatin and 15 μM of the compound (1) of the formula (I) (Y − in the formula (I) is PF 6 − ) is the same as above. Tested. The control was a case where neither cisplatin nor compound (1) was administered, and in Table 2, the number of cells at this time was 10
It is represented by 0. From this table, the compound (1) of the present invention
Shows that it has an effect of proliferating the cancer cell growth inhibitory action of cisplatin by 2 to 3 times more.
【0022】[0022]
【表2】 [Table 2]
【0023】実施例4 U937細胞7×106 個を血清含有RPMI培地1m
lに懸濁し、30℃において培地中の溶存酸素の減少速
度を酸素電極で測定した。一方、同数の細胞を本発明の
化合物(1)(式(I)中Y- はPF6 -)をそのIC50
の約10倍濃度(200μM)に含む培養中で1時間イ
ンキュベート後、上と同様にして酸素減少速度を測定し
たところ、化合物(1)を与えない場合の47%であっ
た。したがって、本発明の化合物(1)には細胞呼吸の
阻害作用がある。なお、シスプラチンの10μM(=I
C50×5)を用いて同様の試験を行ったが有意の呼吸阻
害は認められなかった。Example 4 7 × 10 6 U937 cells were added to 1 m of RPMI medium containing serum.
It was suspended in 1 and the rate of decrease of dissolved oxygen in the medium was measured at 30 ° C. with an oxygen electrode. On the other hand, the same number of cells was treated with the compound (1) of the present invention (wherein Y − is PF 6 − in the formula (I)) as an IC 50.
After incubating for 1 hour in a culture containing about 10 times the concentration (200 μM), the oxygen reduction rate was measured in the same manner as above, and it was 47% of that in the case where compound (1) was not given. Therefore, the compound (1) of the present invention has an inhibitory action on cell respiration. 10 μM of cisplatin (= I
A similar test was conducted using C 50 × 5), but no significant respiratory inhibition was observed.
【0024】[0024]
【発明の効果】以上のように、式(I)の精製クロロオ
スモセニウム塩を有効成分として含む本発明の抗腫瘍剤
はそれ自体強力な癌細胞増殖抑制作用を持つ上に、シス
プラチンとは作用機構を異にしシスプラチンの制癌作用
を増強するという効果を持つ。本発明の抗腫瘍剤は広範
囲の腫瘍細胞の増殖を顕著に抑制する。また本発明の製
造方法によれば、このように作用効果の優れた抗腫瘍剤
を安価にかつ安全に製造することができる。INDUSTRIAL APPLICABILITY As described above, the antitumor agent of the present invention containing the purified chloroosmosenium salt of the formula (I) as an active ingredient has a strong inhibitory effect on the growth of cancer cells, It has a different mechanism of action and has the effect of enhancing the carcinostatic action of cisplatin. The antitumor agent of the present invention remarkably suppresses the growth of a wide range of tumor cells. Further, according to the production method of the present invention, an antitumor agent having such an excellent effect can be produced inexpensively and safely.
───────────────────────────────────────────────────── フロントページの続き (72)発明者 岡 修一 茨城県つくば市東1丁目1番3 工業技術 院生命工学工業技術研究所内 (72)発明者 奥野 洋明 茨城県つくば市東1丁目1番3 工業技術 院生命工学工業技術研究所内 (72)発明者 後藤 みどり 茨城県つくば市東1丁目1番 工業技術院 物質工学工業技術研究所内 ─────────────────────────────────────────────────── ─── Continuation of the front page (72) Inventor Shuichi Oka 1-3-1, East Tsukuba, Ibaraki Industrial Technology Institute of Biotechnology, Institute of Biotechnology (72) Inventor Hiroaki Okuno 1-3-1, East Tsukuba, Ibaraki Industrial Technology Institute of Industrial Science and Technology (72) Inventor Midori Goto 1-1, Higashi, Tsukuba, Ibaraki Prefecture Institute of Industrial Science and Technology, Institute of Materials Engineering
Claims (3)
セニウム塩を有効成分として含有することを特徴とする
抗腫瘍剤。 【化1】 (式中、Yはアニオンを示す。)1. An antitumor agent comprising a chloroosmosenium salt represented by the following formula (I) as an active ingredient. [Chemical 1] (In the formula, Y represents an anion.)
ートイオン(PF6 - )、テトラフルオロボレートイオ
ン、又はピクリン酸イオンであることを特徴とする請求
項1記載の抗腫瘍剤。2. The anion of Y is hexafluorophosphine.
Toion (PF6 - ), Tetrafluoroborate io
Or a picrate ion
Item 1. The antitumor agent according to item 1.
を調製し、これから再結晶により、式(I)で表わされ
る請求項1記載の精製クロロオスモセニウム塩を得るこ
とを特徴とする抗腫瘍剤の製造方法。3. An antitumor characterized in that a saturated aqueous solution of a crude chloroosmosenium salt is prepared and then recrystallized to obtain the purified chloroosmosenium salt represented by the formula (I). Method of manufacturing agent.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP27133193A JP2500368B2 (en) | 1993-10-04 | 1993-10-04 | Antitumor agent |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP27133193A JP2500368B2 (en) | 1993-10-04 | 1993-10-04 | Antitumor agent |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP28689395A Division JP2735155B2 (en) | 1995-11-06 | 1995-11-06 | Method for producing antitumor agent comprising chloroosmosenium salt |
Publications (2)
Publication Number | Publication Date |
---|---|
JPH07101972A true JPH07101972A (en) | 1995-04-18 |
JP2500368B2 JP2500368B2 (en) | 1996-05-29 |
Family
ID=17498568
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
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JP27133193A Expired - Lifetime JP2500368B2 (en) | 1993-10-04 | 1993-10-04 | Antitumor agent |
Country Status (1)
Country | Link |
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JP (1) | JP2500368B2 (en) |
-
1993
- 1993-10-04 JP JP27133193A patent/JP2500368B2/en not_active Expired - Lifetime
Also Published As
Publication number | Publication date |
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JP2500368B2 (en) | 1996-05-29 |
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