JPH0528690B2 - - Google Patents
Info
- Publication number
- JPH0528690B2 JPH0528690B2 JP25128184A JP25128184A JPH0528690B2 JP H0528690 B2 JPH0528690 B2 JP H0528690B2 JP 25128184 A JP25128184 A JP 25128184A JP 25128184 A JP25128184 A JP 25128184A JP H0528690 B2 JPH0528690 B2 JP H0528690B2
- Authority
- JP
- Japan
- Prior art keywords
- substance
- weight
- formula
- administration
- antitumor 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.)
- Expired - Lifetime
Links
- 239000002246 antineoplastic agent Substances 0.000 claims description 6
- 239000004480 active ingredient Substances 0.000 claims description 4
- 150000001875 compounds Chemical class 0.000 claims description 3
- 150000003839 salts Chemical class 0.000 claims description 2
- 239000000126 substance Substances 0.000 description 12
- 206010028980 Neoplasm Diseases 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 4
- 238000009472 formulation Methods 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- UKNGDQSYPNBJAO-UHFFFAOYSA-N Tiaramide hydrochloride Chemical compound Cl.C1CN(CCO)CCN1C(=O)CN1C(=O)SC2=CC=C(Cl)C=C21 UKNGDQSYPNBJAO-UHFFFAOYSA-N 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 208000006268 Sarcoma 180 Diseases 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 230000009036 growth inhibition Effects 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- 238000002054 transplantation Methods 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- -1 5-chloro-2-oxo-3-benzothiazolinyl Chemical group 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 241000854711 Shinkai Species 0.000 description 1
- 125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 description 1
- 239000003708 ampul Substances 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 210000001099 axilla Anatomy 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 235000019658 bitter taste Nutrition 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- DZGCGKFAPXFTNM-UHFFFAOYSA-N ethanol;hydron;chloride Chemical compound Cl.CCO DZGCGKFAPXFTNM-UHFFFAOYSA-N 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 230000007721 medicinal effect Effects 0.000 description 1
- 230000009965 odorless effect Effects 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 239000008213 purified water Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000012439 solid excipient Substances 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000007940 sugar coated tablet Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 230000004614 tumor growth Effects 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Thiazole And Isothizaole Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Description
【発明の詳細な説明】 本発明は抗腫瘍剤に関する。[Detailed description of the invention] The present invention relates to antitumor agents.
具体的には、本発明は、式：
で表わされる化合物又はその塩を活性成分として
含有する抗腫瘍剤に関する。 Specifically, the present invention provides the formula: The present invention relates to an antitumor agent containing a compound represented by the formula or a salt thereof as an active ingredient.
なお、上記式で表わされる本発明物質は、新開
医薬品覧（第２版、1981年、薬業時報社）、日本
医療薬日本医薬品集（第５版、1979年、薬業時報
社）等に、抗炎症作用を有する物質として記載さ
れている公知物質である。 The substance of the present invention represented by the above formula is listed in the Shinkai Pharmaceutical List (2nd edition, 1981, Yakugyo Jihosha), the Japan Pharmaceutical Collection of Medical Drugs (5th edition, 1979, Yakugyo Jihosha), etc. , is a known substance described as having an anti-inflammatory effect.
本物質の代表的な化合物である４−［（５−クロ
ロ−２−オキソ−３−ベンゾチアゾリニル）アセ
チル］−１−ピペラジン エタノール塩酸塩の物
理化学的性質及び毒性は次の通りである。 The physicochemical properties and toxicity of 4-[(5-chloro-2-oxo-3-benzothiazolinyl)acetyl]-1-piperazine ethanol hydrochloride, which is a representative compound of this substance, are as follows. .
分子式 C15H18ClN3O3S・HCl
分子量 392.31
白色の結晶性粉末、無臭、苦味、
水にやや溶けやすく、メタノールまたはエタ
ノールに溶けにくく、エーテルまたはベンゼン
にはほとんど溶けない。Molecular formula C 15 H 18 ClN 3 O 3 S・HCl Molecular weight 392.31 White crystalline powder, odorless, bitter taste, slightly soluble in water, slightly soluble in methanol or ethanol, almost insoluble in ether or benzene.
m.p.約265℃（分解）
水溶液（１→20）のPHは約４、pKaは約6.1
である。mp approx. 265℃ (decomposition) The pH of the aqueous solution (1→20) is approx. 4, and the pKa is approx. 6.1
It is.
LD50（経口、マウス） 564mg／Kg
本物質は、動物又はヒトの腫瘍における腫瘍細
胞数の減少、延命、腫瘍増殖抑制等の効果を有
し、抗腫瘍剤として有用である。LD 50 (oral, mouse) 564mg/Kg This substance has effects such as reducing the number of tumor cells, prolonging life, and inhibiting tumor growth in animal or human tumors, and is useful as an antitumor agent.
本物質を抗腫瘍剤として用いる場合、症状に応
じて薬効を得るのに十分な量の有効成分が含有さ
れた投薬単位形で提供することができる。その形
態としては経口用として散剤、細粒剤、顆粒剤、
錠剤、緩衝剤、糖衣錠剤、カプセル剤、シロツプ
剤、丸剤、懸濁剤、液剤、乳剤などの形態をとり
得る。非経口用として注射液としてのアンプル、
ビンなどの形態をとり得る。座剤、軟膏の形態で
もよい。 When the present substance is used as an antitumor agent, it can be provided in a dosage unit form containing a sufficient amount of the active ingredient to obtain a medicinal effect depending on the symptom. Its forms include powder, fine granules, and granules for oral use.
It can take the form of tablets, buffers, sugar-coated tablets, capsules, syrups, pills, suspensions, solutions, emulsions and the like. Ampoule as injection solution for parenteral use,
It can take the form of a bottle, etc. It may also be in the form of suppositories or ointments.
本物質は単独又は製薬上許容し得る希釈剤及び
他の薬剤と混合して用いてもよく、希釈剤として
固体、液体、半固体の賦形剤、増量剤、結合剤、
湿潤化剤、崩壊剤、表面活性剤、滑沢剤、分散
剤、緩衝剤、香料、保存料、溶解補助剤、溶剤等
が使用され得る。 The substance may be used alone or in admixture with pharmaceutically acceptable diluents and other agents, including solid, liquid, or semi-solid excipients, fillers, binders,
Wetting agents, disintegrants, surfactants, lubricants, dispersants, buffers, fragrances, preservatives, solubilizing agents, solvents, and the like may be used.
本物質を製剤の形で用いる場合、製剤中に活性
成分は一般に0.01〜100重量％、好ましくは0.05
〜80重量％含まれる。 When the substance is used in the form of a formulation, the active ingredient in the formulation is generally 0.01 to 100% by weight, preferably 0.05%.
Contains ~80% by weight.
本物質は人間及び動物に経口的または非経口的
に投与される。経口的投与は舌下投与を包含す
る。非経口的投与は注射投与（例えば皮下、筋
肉、静脈注射、点滴）、直腸投与などを含む。塗
布してもよい。 The substance is administered orally or parenterally to humans and animals. Oral administration includes sublingual administration. Parenteral administration includes injection administration (eg, subcutaneous, intramuscular, intravenous injection, infusion), rectal administration, and the like. May be applied.
本物質の投与量は動物か人間により、また年
齢、個人差、病状などに影響されるので場合によ
つては下記範囲外量を投与する場合もあるが、一
般に人間を対象とする場合、本物質の投与量は１
日当り0.1〜1000mg／Kg、好ましくは１〜300mg／
Kgである。１日２〜４回に分けて投与してもよ
い。 The dose of this substance depends on whether it is an animal or a human, and is influenced by age, individual differences, medical conditions, etc. In some cases, doses outside the range below may be administered, but in general, when administering to humans, The dose of the substance is 1
0.1-1000mg/Kg per day, preferably 1-300mg/
Kg. It may be administered in divided doses 2 to 4 times a day.
以下、実施例により本発明をさらに説明する。 The present invention will be further explained below with reference to Examples.
実施例 １
本物質のSarcoma−180に対する抗腫瘍効果
Sarcoma−180細胞１×106個をICR−JCLマウ
スの腋下部皮下に移植し、移植24時間後より隔日
に10回、0.5％CMC溶液中に溶解もしくは懸濁さ
せた４−［（５−クロロ−２−オキソ−３−ベンゾ
チアゾリニル）アセチル］−１−ピペラジン エ
タノール塩酸塩の所定量（100mg／Kg・回）を経
口投与した。一方、対照群にはCMC溶液のみを
経口投与した。Example 1 Antitumor effect of this substance against Sarcoma-180 1 x 10 6 Sarcoma-180 cells were subcutaneously transplanted into the lower axilla of ICR-JCL mice, and 10 times every other day starting 24 hours after transplantation in 0.5% CMC solution. A predetermined amount (100 mg/Kg/times) of 4-[(5-chloro-2-oxo-3-benzothiazolinyl)acetyl]-1-piperazine ethanol hydrochloride dissolved or suspended in ethanol was administered orally. On the other hand, only the CMC solution was orally administered to the control group.
移植後25日目に腫瘍結節を摘出し、次式に従つ
て各群10匹の腫瘍重量の平均値から増殖抑制率
（I.R.）を算出した。 Tumor nodules were excised on the 25th day after transplantation, and the growth inhibition rate (IR) was calculated from the average tumor weight of 10 animals in each group according to the following formula.
（１−Ｔ／Ｃ）×100＝I.R.（％）
Ｔ：投与群の平均腫瘍重量
Ｃ：対照群の平均腫瘍重量
増殖抑制率41.0％の結果を得た。この結果から
明らかな如く、本物質は腫瘍縮少効果を有し、抗
腫瘍剤として有効であることが確認された。(1-T/C)×100=IR (%) T: Average tumor weight of the administration group C: Average tumor weight of the control group A growth inhibition rate of 41.0% was obtained. As is clear from these results, it was confirmed that this substance has a tumor reduction effect and is effective as an antitumor agent.
製剤化例 １
４−［（５−クロロ−２−オキソ−３−ベンゾチ
アゾリニル）アセチル］−１−ピペラジン エタ
ノール塩酸塩1.5重量部、単シロツプ8.0重量部、
精製水100重量部を加えて、経口剤とした。Formulation Example 1 4-[(5-chloro-2-oxo-3-benzothiazolinyl)acetyl]-1-piperazine 1.5 parts by weight of ethanol hydrochloride, 8.0 parts by weight of single syrup,
100 parts by weight of purified water was added to prepare an oral preparation.
製剤化例 ２
４−［（５−クロロ−２−オキソ−３−ベンゾチ
アゾリニル）アセチル］−１−ピペラジン エタ
ノール塩酸塩を滅菌した生理食塩水に加えて10ml
の注射剤とした。Formulation Example 2 Add 4-[(5-chloro-2-oxo-3-benzothiazolinyl)acetyl]-1-piperazine ethanol hydrochloride to sterilized physiological saline and add 10 ml.
It was made into an injection.
Claims (1)
含有する抗腫瘍剤。[Claims] 1 Formula: An antitumor agent containing the compound represented by or a salt thereof as an active ingredient.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP25128184A JPS61129127A (en) | 1984-11-28 | 1984-11-28 | Antitumor agent |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP25128184A JPS61129127A (en) | 1984-11-28 | 1984-11-28 | Antitumor agent |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS61129127A JPS61129127A (en) | 1986-06-17 |
| JPH0528690B2 true JPH0528690B2 (en) | 1993-04-27 |
Family
ID=17220464
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP25128184A Granted JPS61129127A (en) | 1984-11-28 | 1984-11-28 | Antitumor agent |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS61129127A (en) |
-
1984
- 1984-11-28 JP JP25128184A patent/JPS61129127A/en active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| JPS61129127A (en) | 1986-06-17 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JPH0430924B2 (en) | ||
| JPH0559892B2 (en) | ||
| JPH07277964A (en) | Antitumor agent | |
| JPH0528690B2 (en) | ||
| HUP0203790A2 (en) | Use of compositions containing 6-methoxy-2-naphthylacetic acid prodrugs for treating inflammation | |
| JPH0548207B2 (en) | ||
| JPH03502802A (en) | Antiemetic ergoline derivative | |
| JPH0324446B2 (en) | ||
| JPS61129121A (en) | Antitumor agent | |
| JPS61129128A (en) | Antitumor agent | |
| JPH0528704B2 (en) | ||
| JP2545279B2 (en) | Thrombocytopenia preventive and therapeutic agent | |
| JPH0442368B2 (en) | ||
| JPH0329766B2 (en) | ||
| WO1995020388A1 (en) | Anti-hiv drugs | |
| JPH0120128B2 (en) | ||
| JPH0344049B2 (en) | ||
| JPH0425933B2 (en) | ||
| JPH0528687B2 (en) | ||
| JP2843944B2 (en) | Bile medicine | |
| JPH0649648B2 (en) | Antitumor agent containing acetic acid derivative | |
| JPH0735329B2 (en) | Antitumor agent containing acetic acid derivative | |
| JPH072633B2 (en) | Antitumor agent containing acetic acid derivative | |
| JPH072634B2 (en) | Antitumor agent containing acetic acid derivative | |
| JPH1160483A (en) | Tnf production inhibitor |