JPS61129124A - Antitumor agent - Google Patents

Abstract

PURPOSE:An antitumor agent comprising a specific compound including well- known benzydamine hydrochloride well-known as an anti-inflammatory agent, as an active ingredient. CONSTITUTION:A compound shown by the formula I (R1 and R2 are H, 1-4C alkyl, halogen, or methoxy; n is 1-4) is used as an antitumor agent. Especially benzydamine derivative shown by the formula II is a representative compound. the compound shown by the formula I is found to have effects or reduction in number of tumor cells, prolongation of life, and inhibition of tumor multiplica tion, etc. in tumor of animal and human, and to be useful as an antitumor agent. A dosage form for administration may be either oral or parenteral admin istration. A dose is preferably 0.1-300mg/kg/day.

Description

【発明の詳細な説明】 本発明は抗！！瘍剤に関する。[Detailed description of the invention] This invention is anti! ! Regarding cancer drugs.

本発明は、下記一般式（１）で表わされる化合物又はそ
の塩および該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。The present invention relates to a compound represented by the following general formula (1) or a salt thereof, and an antitumor agent containing the compound or a salt thereof as an active ingredient.

（式中、Ｒ１及びＲ２は夫々Ｈ１炭素数１〜４のアルキ
ル、ハロゲン又はメトキシであり、ｎは１〜４である） なお、上記一般式（１）で表わされる本発明物質の中に
は、医薬品要覧　総合新版、７０〜１０１頁、薬業時報
社（昭和５４年５月１５日出版）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も含まれる。(In the formula, R1 and R2 are each H1 alkyl having 1 to 4 carbon atoms, halogen, or methoxy, and n is 1 to 4.) Note that among the substances of the present invention represented by the above general formula (1), Also included are known substances described as substances having anti-inflammatory effects in , Pharmaceutical Handbook General New Edition, pp. 70-101, Yakugyo Jihosha (published on May 15, 1978).

本物質の代表的な化合物であるベンジダミン塩酸塩（一
般式（１）中Ｒ及びＲ２が共にＨで、ｎが３の化合物で
ある）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 benzydamine hydrochloride (a compound in which R and R2 are both H and n is 3 in general formula (1)), which is a representative compound of this substance, are as follows.

白色〜淡黄白色の結晶または結品性粉末、π奥。White to pale yellowish-white crystals or crystalline powder, π deep.

味は苦く舌をまひする。The taste is bitter and numbs the tongue.

水に極めて溶けやすく、エタノール、クロロホルムまた
は氷酢酸に溶けやすく、アセトンに溶りにくく、エーテ
ルには極めて溶けにくい。Very soluble in water, soluble in ethanol, chloroform or glacial acetic acid, sparingly soluble in acetone, very sparingly soluble in ether.

ｍ、ｐ、　　１５８〜１６１℃ １−Ｄ５ｏ（経口、マウス）５４０＃ＩｓＦ／に９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。m, p, 158-161°C 1-D5o (oral, mouse) 540#IsF/9 This substance reduces the number of tumor cells in animal or human tumors,
It has effects such as prolonging life and suppressing tumor growth, 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、緩衝錠、糖衣錠剤、カ
プセル剤、シロップ剤、乳剤、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。療剤、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. For oral use, it can take the form of powders, fine granules, granules, tablets, buffered tablets, sugar-coated tablets, capsules, syrups, emulsions, suspensions, solutions, emulsions, and the like. For parenteral use, it can be in the form of an ampule or bottle as an injection solution. It may also be in the form of a therapeutic agent or ointment.

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, disintegrating agents, etc. agents, surfactants, lubricants, dispersants, buffers, fragrances, preservatives, solubilizing agents, solvents, etc. 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ｏ、　ｏｉ〜１００重る％、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 comprised between o, oi and 100% by weight, preferably between 0.05 and 100% by weight.
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−目的投与は舌下投与を包含する。The substance is administered orally or parenterally to humans and animals. Oral-target administration includes sublingual administration.

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。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っては下記範囲外
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　０．１〜５００ａｙ／
Ｋｇ、好ましくは１〜３００Ｒｇ／に９である。１日２
〜４回に分けて投与してもよい。The dosage 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 shown below may be administered, but in general, when administering this substance to humans, Dosage is 0.1 to 500 ay/day
Kg, preferably 1 to 300 Rg/9. 1 day 2
It may be administered in ~4 divided doses.

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.

Ｓ　ａｒｃＯＩＩｌａ　−１８０＠胞１×１０６個をＩ
ＣＲ−ＪＣＬマウスの腋下部皮下に移植し、移植２４時
時間上り隔日に１０回、０．５％ＣＭＧ溶液中に溶解も
しくは懸濁させたベンジダミン塩酸塩の所定量（２００
ＩＩＪ／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。S arcOIIla -180@1 x 106 cells I
A predetermined amount of benzydamine hydrochloride dissolved or suspended in a 0.5% CMG solution (200
IIJ/Kg・times) was orally administered. On the other hand, only the CMC solution was orally administered to the control group.

移植後２５日目に！！瘍結節を摘出し、次式に従って各
群１０匹の腫瘍宙吊の平均値から増殖抑制率（１，Ｒ，
）を算出した。25th day after transplant! ! The tumor nodules were excised, and the growth inhibition rate (1, R,
) was calculated.

（１−Ｔ／Ｃ）Ｘ１００　＝　１．Ｒ，（％）Ｔ：投与
群の平均ＩＩ！瘍重中 重量対照群の平均腫瘍重量 増殖抑制率６０．４％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)X100 = 1. R, (%) T: Average II of administration group! An average tumor weight growth inhibition rate of 60.4% was obtained for the medium tumor weight control group. 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Ｊ目Ｌ］」− ベンジダミン塩酸塩１５重量部、弔シロップ８０重量部
、精製水１００重准部を加えて、経口剤とした。15 parts by weight of benzydamine hydrochloride, 80 parts by weight of funeral syrup, and 100 parts by weight of purified water were added to prepare an oral preparation.

笈ＪＬＬ乳ユ ベンジダミン塩酸塩を滅菌した生理食塩水に加えて１０
ｄの注射剤とした。Add JLL milk jubenzydamine hydrochloride to sterile saline and add 10
It was used as an injection of d.

Claims (2)

【特許請求の範囲】[Claims] （１）一般式 ▲数式、化学式、表等があります▼ （式中、Ｒ＿１及びＲ＿２は夫々Ｈ、炭素数１〜４のア
ルキル、ハロゲン又はメトキシであり、ｎは１〜４であ
る） で表わされる化合物を活性成分として含有する抗腫瘍剤
。(1) General formula ▲ There are mathematical formulas, chemical formulas, tables, etc. An antitumor agent containing a compound as an active ingredient. （２）式 ▲数式、化学式、表等があります▼ で表わされる化合物を活性成分として含有する特許請求
の範囲第１項に記載の抗腫瘍剤。(2) The antitumor agent according to claim 1, which contains a compound represented by the formula ▲ which includes mathematical formulas, chemical formulas, tables, etc. as an active ingredient.