JPH06122623A - Antineoplastic agent - Google Patents
Antineoplastic agentInfo
- Publication number
- JPH06122623A JPH06122623A JP27205392A JP27205392A JPH06122623A JP H06122623 A JPH06122623 A JP H06122623A JP 27205392 A JP27205392 A JP 27205392A JP 27205392 A JP27205392 A JP 27205392A JP H06122623 A JPH06122623 A JP H06122623A
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- formula
- hydroxychalcone
- chalcone
- chalcone compound
- chemical
- Prior art date
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- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
Description
【０００１】[0001]
【産業上の利用分野】本発明は、抗腫瘍剤に関し、詳し
くは、カルコン化合物を有効成分として含有し、腫瘍細
胞増殖抑制作用及び発ガンプロモーター抑制作用を有す
る抗腫瘍剤を提供するものである。TECHNICAL FIELD The present invention relates to an antitumor agent, and more specifically to an antitumor agent containing a chalcone compound as an active ingredient and having a tumor cell growth inhibitory action and a carcinogenic promoter inhibitory action. .
【０００２】[0002]
【従来の技術】生薬中に存在するフラボノイド類（例え
ばクエルセチン、アピゲニン、リクイリチゲニン等）
が、腫瘍細胞増殖抑制作用あるいは発ガンプロモーター
抑制作用を有することが報告されている。BACKGROUND OF THE INVENTION Flavonoids present in crude drugs (for example, quercetin, apigenin, liquiritigenin, etc.)
However, it has been reported to have a tumor cell growth inhibitory action or a cancer promoter inhibitory action.
【０００３】しかし、これらの化合物は生薬より抽出、
分離し、さらに精製しなければならない。また、化学合
成により得ようとすると、数段階の工程が必要であり、
合成法によっては一旦カルコン誘導体を作り、それを閉
環させる必要がある。However, these compounds are extracted from crude drugs,
It must be separated and further purified. In addition, when trying to obtain it by chemical synthesis, several steps are required,
Depending on the synthetic method, it is necessary to make a chalcone derivative once and then close it.
【０００４】[0004]
【発明が解決しようとする課題】上述したように、従来
の方法でフラボノイド化合物を得るには、複雑な作業あ
るいは多段階の工程が必要である。As described above, in order to obtain a flavonoid compound by the conventional method, complicated work or multi-step process is required.
【０００５】本発明は、上記観点からなされたものであ
り、複雑な作業を必要とせず、短い工程で有効な化合物
を得ることを課題とする。The present invention has been made from the above viewpoint, and an object thereof is to obtain an effective compound in a short process without requiring complicated work.
【０００６】[0006]
【課題を解決するための手段】本発明者は、上記課題を
解決するために、生薬中に存在し抗腫瘍活性を有する物
質を検索している過程で、新彊甘草抽出物に含まれるリ
コカルコンＡが有効であることを見出し、さらにその関
連化合物でより効力が高く、合成も行いやすいカルコン
を鋭意探索した結果、有効な化合物を開発することに成
功し、本発明に至った。[Means for Solving the Problems] In order to solve the above problems, the present inventor has searched for a substance having an antitumor activity which is present in a herbal medicine, and in the process of lycochalcone contained in Shinji licorice extract. As a result of finding that A is effective and further searching for chalcone which is more effective and easier to synthesize with its related compound, we succeeded in developing an effective compound and reached the present invention.
【０００７】すなわち本発明は化１で表されるカルコン
化合物を有効成分として含有する抗腫瘍剤、及び化８で
表されるリコカルコンＡを有効成分として含有する抗腫
瘍剤である。That is, the present invention is an antitumor agent containing the chalcone compound represented by Chemical formula 1 as an active ingredient, and an antitumor agent containing lycochalcone A represented by Chemical formula 8 as an active ingredient.
【０００８】以下、本発明を詳細に説明する。 ＜１＞本発明に用いるカルコン化合物 上述したように、本発明の抗腫瘍剤は、化９で表される
カルコン化合物、あるいはリコカルコンＡを有効成分と
して含有するものである。The present invention will be described in detail below. <1> Chalcone Compound Used in the Present Invention As described above, the antitumor agent of the present invention contains the chalcone compound represented by Chemical formula 9 or lycochalcone A as an active ingredient.
【０００９】[0009]
【化９】 [Chemical 9]
【００１０】但し、式中Ｒは−ＯＨ又は−ＣＨ3を、Ｒ1
は−Ｈ、−ＯＨ、−ＯＣＨ3、−ＣＨ3のいずれかを、Ｒ
2は−Ｈ又は−ＣＨ3をそれぞれ表す。上記カルコン化合
物としては、化２で表される３−ハイドロキシカルコ
ン、化３で表される３，３’−ジハイドロキシカルコ
ン、化４で表される３’−メトキシ−３−ハイドロキシ
カルコン、化５で表される３’−メチル−３−ハイドロ
キシカルコン、化６で表される３’−ハイドロキシ−３
−メチルカルコン、化７で表される３−ハイドロキシ−
４’−メチルカルコン等が挙げられる。However, in the formula, R represents --OH or --CH 3 and R 1
Is -H, -OH, -OCH 3, one of the -CH 3, R
2 respectively represent -H or -CH 3. Examples of the chalcone compound include 3-hydroxychalcone represented by Chemical formula 2, 3,3′-dihydroxychalcone represented by Chemical formula 3, 3′-methoxy-3-hydroxychalcone represented by Chemical formula 4, and Chemical formula 5 3'-methyl-3-hydroxychalcone represented by the formula, 3'-hydroxy-3 represented by the formula 6
-Methylchalcone, 3-hydroxy represented by Chemical formula 7
4'-methyl chalcone and the like can be mentioned.
【００１１】本発明に用いるカルコン化合物及びリコカ
ルコンＡは、必要に応じてその塩として提供することも
可能である。例えば、ナトリウム塩、カリウム塩等が例
示できる。The chalcone compound and lycochalcone A used in the present invention can be provided as salts thereof, if necessary. For example, sodium salt, potassium salt and the like can be exemplified.
【００１２】尚、３’−メチル−３−ハイドロキシカル
コン、３’−ハイドロキシ−３−メチルカルコンは新規
化合物である。以下に、３’−メチル−３−ハイドロキ
シカルコンの物性を示す。3'-Methyl-3-hydroxychalcone and 3'-hydroxy-3-methylchalcone are novel compounds. The physical properties of 3'-methyl-3-hydroxychalcone are shown below.
【００１３】 融点 ： １０６〜１０７℃ 質量スペクトル ％Int ｍ／ｚ ２３８（Ｍ+） （base） ｍ／ｚ ２３７ （59.0） ｍ／ｚ １４７ （22.0） ｍ／ｚ １１９ （28.3） 高分解能質量スペクトル 計算値 ： ２３８．０９９４ 測定値 ： ２３８．０９９４Melting point: 106-107 ° C. Mass spectrum% Int m / z 238 (M + ) (base) m / z 237 (59.0) m / z 147 (22.0) m / z 119 (28.3) High-resolution mass spectrum calculation Value: 238.0994 Measured value: 238.0994
【００１４】＜２＞本発明に用いるカルコン化合物の製
法 上記カルコン化合物は、すべて常法による化学合成で得
られる。以下に製造法を示す。<2> Method for Producing Chalcone Compound Used in the Present Invention All the above chalcone compounds can be obtained by chemical synthesis by a conventional method. The manufacturing method is shown below.
【００１５】化１０に示すように、目的化合物に必要な
官能基を有するアセトフェノンと、同じく必要な官能基
を有するベンズアルデヒドをクライゼン−シュミット縮
合させることにより、前記カルコン化合物が得られる。
尚、官能基の種類に応じて、必要に応じてその官能基に
保護を行い縮合させた後、脱保護し目的化合物を得る。As shown in Chemical formula 10, the chalcone compound can be obtained by Claisen-Schmidt condensation of acetophenone having a functional group necessary for the target compound and benzaldehyde having a functional group necessary for the target compound.
Depending on the type of the functional group, the functional group may be protected and condensed if necessary, and then deprotected to obtain the target compound.
【００１６】[0016]
【化１０】 [Chemical 10]
【００１７】但し、Ｒ1は−Ｈ、−ＯＨ、−ＯＣＨ3又は
−ＣＨ3、Ｒ2は−Ｈ、−ＯＨ又は−ＣＨ3を表す。次
に、製造法の一例として、３’−メチル−３−ハイドロ
キシカルコンの製造例を示す。However, R 1 represents —H, —OH, —OCH 3 or —CH 3 , and R 2 represents —H, —OH or —CH 3 . Next, a production example of 3′-methyl-3-hydroxychalcone will be shown as an example of the production method.
【００１８】ｍ−ハイドロキシベンズアルデヒド５ｇを
アセトニトリル１５０ｍｌに溶解し、更に１８−クラウ
ン−６−エーテル１ｇ及びクロルジメチルエーテル５ｍ
ｌを加え、室温でしばらく撹伴した後、無水炭酸カリウ
ム２５ｇを撹拌しながら加え、一時間反応を続けた。5 g of m-hydroxybenzaldehyde was dissolved in 150 ml of acetonitrile, and further 1 g of 18-crown-6-ether and 5 m of chlorodimethyl ether.
l was added, and the mixture was stirred at room temperature for a while, 25 g of anhydrous potassium carbonate was added with stirring, and the reaction was continued for 1 hour.
【００１９】反応液を濾過した後、濾液を減圧濃縮し、
ジエチルエーテル−水で分配し、エーテル層を分取し
た。得られたエーテル層を硫酸ナトリウムを用いて６時
間乾燥させた後、硫酸ナトリウムを濾過除去し、溶媒を
４０℃以下で留去した。得られた残渣をシリカゲルクロ
マトグラフィー（溶媒 ヘキサン：酢酸エチル＝９：
１）により分離し、ｍ−メトキシメトキシベンズアルデ
ヒド５．５ｇを得た。After filtering the reaction solution, the filtrate is concentrated under reduced pressure,
The mixture was partitioned with diethyl ether-water, and the ether layer was separated. The obtained ether layer was dried with sodium sulfate for 6 hours, sodium sulfate was removed by filtration, and the solvent was distilled off at 40 ° C or lower. The obtained residue was chromatographed on silica gel (solvent hexane: ethyl acetate = 9:
Separation according to 1) gave 5.5 g of m-methoxymethoxybenzaldehyde.
【００２０】このようにして得られたｍ−メトキシメト
キシベンズアルデヒド５．５ｇとｍ−メチルアセトフェ
ノン４．５ｇをエタノール４０ｍｌに溶解し、更に２５
％水酸化カリウム水溶液２０ｍｌを加え、室温にて２４
時間撹拌した。5.5 g of m-methoxymethoxybenzaldehyde thus obtained and 4.5 g of m-methylacetophenone were dissolved in 40 ml of ethanol, and further dissolved in 25 ml.
% Potassium hydroxide aqueous solution 20ml, at room temperature 24
Stir for hours.
【００２１】反応終了後、反応液をＩＮ ＨＣｌで中和
し、減圧濃縮した後に、ジエテルエーテル−水で分配
し、エーテル層を硫酸ナトリウムを用いて６時間乾燥さ
せた。乾燥後、硫酸ナトリウムを濾過除去し、溶媒を４
０℃以下で留去した後、残渣をシリカゲルカラムクロマ
トグラフィー（展開溶媒 ヘキサン：酢酸エチル＝４：
１）により分離し、３−メトキシメトキシ−３’−メチ
ルカルコンを得た。After the reaction was completed, the reaction solution was neutralized with IN HCl, concentrated under reduced pressure, partitioned with diethyl ether-water, and the ether layer was dried with sodium sulfate for 6 hours. After drying, the sodium sulfate was removed by filtration, and the solvent was added to 4
After distilling off at 0 ° C. or lower, the residue was subjected to silica gel column chromatography (developing solvent hexane: ethyl acetate = 4:
Separation by 1) gave 3-methoxymethoxy-3'-methylchalcone.
【００２２】得られた３−メトキシメトキシ−３’−メ
チルカルコン３ｇをメタノール６０ｍｌに溶解し、３Ｎ
−ＨＣｌ ２０ｍｌを加え、３０分間煮沸還流を行っ
た。反応終了後、反応液を減圧濃縮し、ジエテルエーテ
ル−水で分配し、エーテル層を硫酸ナトリウムで乾燥さ
せた。3 g of the obtained 3-methoxymethoxy-3'-methylchalcone was dissolved in 60 ml of methanol to obtain 3N.
-HCI 20ml was added and it boiled and refluxed for 30 minutes. After completion of the reaction, the reaction solution was concentrated under reduced pressure, partitioned with diethyl ether-water, and the ether layer was dried over sodium sulfate.
【００２３】硫酸ナトリウムを濾過除去し、溶媒を留去
した後、残渣を少量のメタノールに溶解し、オクタデシ
ルシリル（ＯＤＳ）カラムを用いて高速液体クロマトグ
ラフィー（溶媒 メタノール：水＝７５：２５）により
分取した。カルコン化合物の検出は、２５４ｎｍで吸光
度を測定することにより行った。得られた画分をメタノ
ール：水にて再結晶させることにより、３’−メチル−
３−ハイドロキシカルコン１．５ｇを得た。After sodium sulfate was removed by filtration and the solvent was distilled off, the residue was dissolved in a small amount of methanol and subjected to high performance liquid chromatography (solvent methanol: water = 75: 25) using an octadecylsilyl (ODS) column. I collected it. Detection of the chalcone compound was performed by measuring the absorbance at 254 nm. By recrystallizing the obtained fraction with methanol: water, 3'-methyl-
1.5 g of 3-hydroxychalcone was obtained.
【００２４】＜３＞本発明の抗腫瘍剤 本発明の抗腫瘍剤は、上記カルコン化合物あるいはリコ
カルコンＡから選ばれる１種又はそれ以上を有効成分と
して含有するものであり、剤型、製法は特に問わず、常
法により製造される。<3> Antitumor Agent of the Present Invention The antitumor agent of the present invention contains, as an active ingredient, one or more selected from the above chalcone compound or lycochalcone A, and its formulation and manufacturing method are particularly Regardless, it is manufactured by a conventional method.
【００２５】例えば、製剤上許容される無害の一種、或
は数種の賦形剤、例えば、乳糖、バレイショデンプン、
炭酸カルシウム、又はアルギン酸ナトリウム等を配剤し
た散剤、顆粒剤、錠剤、カプセル剤等とすることができ
る。また、注射剤とする場合は、溶媒は注射用蒸留水、
又はポリエチレングリコール等が使用され、或はこれに
分散剤を添加してもよい。For example, one or several non-toxic pharmaceutically acceptable excipients such as lactose, potato starch,
It can be made into powders, granules, tablets, capsules and the like in which calcium carbonate, sodium alginate or the like is dispensed. Also, when preparing an injection, the solvent is distilled water for injection,
Alternatively, polyethylene glycol or the like is used, or a dispersant may be added thereto.
【００２６】投与方法としては、経口、非経口のいずれ
も選択できる。投与量は、患者の年齢、症状等により異
なるが、一般には経口投与では成人１人１日当り、カル
コン化合物の量として、０．０１〜１００ｍｇの範囲で
用いることにより、所期の効果が期待できる。また、非
経口の場合の投与量は成人１人１日当り上記経口投与の
６０％の量が適当である。The method of administration may be oral or parenteral. The dose varies depending on the age, symptoms, etc. of the patient, but generally, by oral administration, the desired effect can be expected by using the amount of the chalcone compound in the range of 0.01 to 100 mg per adult per day. . In the case of parenteral administration, 60% of the above oral administration per adult per day is appropriate.
【００２７】[0027]
【作用】以下に、本発明に用いるカルコン化合物の作用
を示す。 ＜腫瘍細胞増殖抑制作用＞本発明に用いるカルコン化合
物及びリコカルコンＡが、イン・ビトロにおける各種腫
瘍細胞の増殖を抑制するか否かを指標として、腫瘍細胞
増殖抑制作用の評価を行った。The action of the chalcone compound used in the present invention will be described below. <Tumor Cell Proliferation Inhibitory Action> The tumor cell proliferation inhibitory action was evaluated by using as an index whether the chalcone compound and lycochalcone A used in the present invention inhibit the proliferation of various tumor cells in vitro.
【００２８】（１）胃癌に対する効果 ヒト胃癌ＨＧＣ−２７細胞を直径３．５ｃｍのディシュ
に播いて培養を行い、培養１日後にこの培養液中に化２
〜７で表される各カルコン化合物、あるいはリコカルコ
ンＡを１μｇ/ｍｌの濃度になるように添加した。(1) Effect on gastric cancer Human gastric cancer HGC-27 cells were sown on a dish having a diameter of 3.5 cm and cultured, and after 1 day of culturing, the cells were transformed into this culture medium.
Each of the chalcone compounds represented by ~ 7 or lycochalcone A was added so as to have a concentration of 1 µg / ml.
【００２９】３日間培養を続けた後、細胞数を測定し、
増殖抑制率を算出した。結果を表１に示す。After culturing for 3 days, the number of cells was measured,
The growth inhibition rate was calculated. The results are shown in Table 1.
【００３０】[0030]
【表１】 [Table 1]
【００３１】いずれのカルコン化合物も、強い増殖抑制
効果を示すことが明かとなった。その中でも３’−メチ
ル−３−ハイドロキシカルコンが最も効力が強かった。It was revealed that each of the chalcone compounds exhibited a strong antiproliferative effect. Among them, 3'-methyl-3-hydroxychalcone was most effective.
【００３２】（２）ＨＧＣ−２７細胞の増殖に及ぼす
３’−メチル−３−ハイドロキシカルコンの作用 ＨＧＣ−２７細胞を直径３．５ｃｍのディシュに播き、
培養１日後、種々の濃度の３’−メチル−３−ハイドロ
キシカルコンを添加し、さらに１〜４日間培養を行った
後、細胞数を測定した。結果を図１に示した。(2) Effect of 3'-methyl-3-hydroxychalcone on proliferation of HGC-27 cells HGC-27 cells were seeded on a dish having a diameter of 3.5 cm,
After 1 day of culture, various concentrations of 3'-methyl-3-hydroxychalcone were added, and the cells were further cultured for 1 to 4 days, and then the number of cells was measured. The results are shown in Fig. 1.
【００３３】３’−メチル−３−ハイドロキシカルコン
は、濃度依存的にＨＧＣ−２７細胞の増殖を抑制し、処
理後３日目におけるＩＤ50は約０．５μｇ/ｍｌである
ことが判明した（図１）。It was found that 3'-methyl-3-hydroxychalcone suppressed the proliferation of HGC-27 cells in a concentration-dependent manner, and the ID 50 on the third day after the treatment was about 0.5 μg / ml ( (Fig. 1).
【００３４】また１μｇ/ｍｌの濃度でも本カルコン化
合物は、ＨＧＣ−２７細胞の増殖を完全に抑制し、その
効力は少なくとも４日間継続した（図２）。The chalcone compound completely suppressed the proliferation of HGC-27 cells even at a concentration of 1 μg / ml, and its efficacy was continued for at least 4 days (FIG. 2).
【００３５】（３）種々のヒト腫瘍細胞に対する３’−
メチル−３−ハイドロキシカルコンの作用 子宮頸癌由来ＨｅＬａ細胞、神経芽細胞腫由来ＧＯＴＯ
細胞および膵癌由来ＰＡＮＣ−１細胞を直径３．５ｃｍ
のディシュに４×１０４4個ずつ播き、培養を行った。
１日後、それぞれの培養液に化合物（４）を１μｇ/の
濃度になるように添加し、３日間培養を継続し細胞数を
測定した。結果を表２に示す。(3) 3'- for various human tumor cells
Action of methyl-3-hydroxychalcone HeLa cells derived from cervical cancer, GOTO derived from neuroblastoma
Cells and pancreatic cancer-derived PANC-1 cells with a diameter of 3.5 cm
4 × 10 4 cells were seeded on each dish and cultured.
After 1 day, the compound (4) was added to each culture solution to a concentration of 1 μg /, and the culture was continued for 3 days to measure the number of cells. The results are shown in Table 2.
【００３６】[0036]
【表２】 [Table 2]
【００３７】以上の結果から、３’−メチル−３−ハイ
ドロキシカルコンは、いずれのヒト腫瘍細胞に対しても
増殖抑制効果を示すことがわかった。From the above results, it was found that 3'-methyl-3-hydroxychalcone exhibited a growth inhibitory effect on any human tumor cells.
【００３８】＜２＞発ガンプロモーター抑制効果 発ガンプロモーターには種々の物質が知られており、そ
の中でも１２−Ｏ−テトラデカノイルフォルボール−１
３−アセテート（ＴＰＡ）は最も強力なものの一つであ
る。<2> Inhibitory effect of carcinogenic promoter Various substances are known as carcinogenic promoters, and among them, 12-O-tetradecanoylphorbol-1.
3-acetate (TPA) is one of the most powerful.
【００３９】ＴＰＡの作用機序の全貌は現在でもなお不
明であるが、細胞のリン脂質代謝の亢進は、発ガンプロ
モーションにつながる重要な要因の一つであると考えら
れており、ＴＰＡの作用を抑制する化合物の多くのもの
が、ＴＰＡによる発癌プロモーションを阻止し、腫瘍の
発生を効率よく低下させることが明確になっている。Although the entire mechanism of action of TPA is still unknown at present, the enhancement of phospholipid metabolism in cells is considered to be one of the important factors leading to carcinogenic promotion, and the action of TPA It has been clarified that many of the compounds that suppress the tumorigenesis block the carcinogenic promotion by TPA and efficiently reduce the tumorigenesis.
【００４０】そこで今回開発したカルコン化合物の抗プ
ロモーター作用の指標として、ＴＰＡによる細胞のリン
脂質代謝亢進を抑制する効力を測定した。ＴＰＡによっ
て引き起こされる、細胞のリン脂質合成亢進をカルコン
化合物が抑制する作用について培養細胞を用いたイン・
ビトロの系で検定した。Therefore, as an index of the anti-promoter action of the chalcone compound developed this time, the efficacy of suppressing the phospholipid metabolism promotion of cells by TPA was measured. The effect of chalcone compounds on the inhibition of phospholipid synthesis enhancement of cells caused by TPA
The test was performed in vitro.
【００４１】被験化合物を５μｇ/ｍｌの濃度になるよ
うにＨｅＬａ細胞培養液中に添加した。対照には、主実
験に用いたのと同量の溶媒のみを添加した。１時間後に
ＴＰＡ（５０ｎＭ）及び放射性無機リン酸32Ｐｉを加
え、さらに４時間培養を続けた。その後細胞のリン脂質
を抽出し、放射活性を測定し、ＴＰＡによって促進され
た放射活性取り込みをどれほど抑制したかを算出した。
結果を表３に示す。The test compound was added to the HeLa cell culture medium at a concentration of 5 μg / ml. For the control, only the same amount of solvent used in the main experiment was added. After 1 hour, TPA (50 nM) and radioactive inorganic phosphate 32 Pi were added, and the culture was continued for another 4 hours. Then, the phospholipids of the cells were extracted, the radioactivity was measured, and it was calculated how much the radioactivity uptake promoted by TPA was suppressed.
The results are shown in Table 3.
【００４２】[0042]
【表３】 [Table 3]
【００４３】いずれのカルコン化合物も、ＴＰＡによっ
て亢進する32Ｐｉ取り込みを抑制することが明かとなっ
た。その中でも３’−メチル−３−ハイドロキシカルコ
ンは、特に強力な抗プロモーター活性を持つことが判明
した。It was revealed that all chalcone compounds suppressed the 32 Pi uptake promoted by TPA. Among them, 3'-methyl-3-hydroxychalcone was found to have a particularly strong antipromoter activity.
【００４４】[0044]
【実施例】以下に、本発明の実施例を説明する。EXAMPLES Examples of the present invention will be described below.
【００４５】[0045]
【製剤例１】錠剤 １錠当り５ｍｇのカルコン化合物を含有する錠剤を以下
のようにして製造する。 （製法）カルコン化合物の結晶を粉砕し、それに乳糖及
び澱粉を加え混合する。１０％の澱粉のりを上記の混合
体に加え、撹拌し顆粒を製造する。乾燥後粒径を約８５
０ミクロンに製粒し、これにタルク及びステアリン酸マ
グネシウムを混合し、打錠する。[Formulation Example 1] Tablet A tablet containing 5 mg of chalcone compound per tablet is produced as follows. (Production method) Crystals of the chalcone compound are crushed, and lactose and starch are added thereto and mixed. 10% starch paste is added to the above mixture and stirred to produce granules. Particle size after drying is about 85
Granulate to 0 micron, mix with talc and magnesium stearate and tablet.
【００４６】[0046]
【製剤例２】カプセル剤 １カプセル当り２０ｍｇのカルコン化合物を含有するカ
プセル剤を以下のようにして製造する。 （製法）カルコン化合物をよく粉砕し、澱粉、乳糖及び
ステアリン酸マグネシウムを加え、充分に混合した後カ
プエルに充填する。[Formulation Example 2] Capsule A capsule containing 20 mg of chalcone compound per capsule is produced as follows. (Manufacturing method) The chalcone compound is well pulverized, starch, lactose and magnesium stearate are added, mixed well, and then filled in a capel.
【００４７】[0047]
【製剤例３】注射液 注射液を、以下のようにして製造する。 （製法）カルコン化合物を、マクロゴール４０００及び
塩化ナトリウムの処方量を含む蒸留水に溶解させ、ｐＨ
を７．０付近に調整した後アンプルに充填熔封する。[Formulation Example 3] Injection solution An injection solution is produced as follows. (Manufacturing method) The chalcone compound is dissolved in distilled water containing Macrogol 4000 and a prescribed amount of sodium chloride to adjust the pH.
After adjusting to around 7.0, fill and seal the ampoule.
【００４８】[0048]
【発明の効果】本発明の抗腫瘍剤は、強い腫瘍細胞増殖
抑制効果、及び抗発ガンプロモーター活性を併せ持って
いる。この効果により、癌の予防及び治療など癌に対す
る総合的な対策を可能になる。The antitumor agent of the present invention has both a strong tumor cell growth inhibitory effect and an anticarcinogenic promoter activity. This effect enables comprehensive measures against cancer such as prevention and treatment of cancer.
【図１】 カルコン化合物濃度に対する腫瘍細胞抑制作
用の変化を示す図FIG. 1 is a graph showing changes in tumor cell inhibitory effect on chalcone compound concentration.
【図２】 カルコン化合物存在下での腫瘍細胞の増殖抑
制を示す図FIG. 2 is a diagram showing suppression of tumor cell growth in the presence of a chalcone compound.
Claims (8)
分として含有する抗腫瘍剤。 【化１】 但し、式中Ｒは−ＯＨ又は−ＣＨ3を、Ｒ1は−Ｈ、−Ｏ
Ｈ、−ＯＣＨ3、−ＣＨ3のいずれかを、Ｒ2は−Ｈ又は
−ＣＨ3をそれぞれ表す。1. An antitumor agent containing the chalcone compound represented by Chemical formula 1 as an active ingredient. [Chemical 1] However, in the formula, R is —OH or —CH 3 , and R 1 is —H, —O.
H, -OCH 3, one of -CH 3, R 2 represents respectively -H or -CH 3.
３−ハイドロキシカルコンである請求項１記載の抗腫瘍
剤。 【化２】 2. The antitumor agent according to claim 1, wherein the chalcone compound is 3-hydroxychalcone represented by Chemical formula 2. [Chemical 2]
３，３’−ジハイドロキシカルコンである請求項１記載
の抗腫瘍剤。 【化３】 3. The antitumor agent according to claim 1, wherein the chalcone compound is 3,3′-dihydroxychalcone represented by Chemical formula 3. [Chemical 3]
３’−メトキシ−３−ハイドロキシカルコンである請求
項１記載の抗腫瘍剤。 【化４】 4. The antitumor agent according to claim 1, wherein the chalcone compound is 3′-methoxy-3-hydroxychalcone represented by Chemical formula 4. [Chemical 4]
３’−メチル−３−ハイドロキシカルコンである特許請
求の範囲第１項に記載の抗腫瘍剤。 【化５】 5. The antitumor agent according to claim 1, wherein the chalcone compound is 3′-methyl-3-hydroxychalcone represented by Chemical formula 5. [Chemical 5]
３’−ハイドロキシ−３−メチルカルコンである請求項
１記載の抗腫瘍剤。 【化６】 6. The antitumor agent according to claim 1, wherein the chalcone compound is 3′-hydroxy-3-methylchalcone represented by Chemical formula 6. [Chemical 6]
ハイドロキシ−４’−メチルカルコンである特許請求の
範囲第１項に記載の抗腫瘍剤。 【化７】 7. A chalcone compound represented by Chemical formula 3
The antitumor agent according to claim 1, which is hydroxy-4'-methylchalcone. [Chemical 7]
分として含有する抗腫瘍剤。 【化８】 8. An antitumor agent containing Lycochalcone A represented by Chemical formula 8 as an active ingredient. [Chemical 8]
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP27205392A JPH06122623A (en) | 1992-10-09 | 1992-10-09 | Antineoplastic agent |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP27205392A JPH06122623A (en) | 1992-10-09 | 1992-10-09 | Antineoplastic agent |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH06122623A true JPH06122623A (en) | 1994-05-06 |
Family
ID=17508457
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP27205392A Pending JPH06122623A (en) | 1992-10-09 | 1992-10-09 | Antineoplastic agent |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH06122623A (en) |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2001046110A3 (en) * | 1999-12-23 | 2002-02-21 | Univ Georgia Res Found | Chalcone and its analogs as agents for the inhibition of angiogenesis and related disease states |
| FR2826549A1 (en) * | 2001-06-28 | 2003-01-03 | Roquette Freres | PROCESS FOR THE PREPARATION OF A COMPRESSED EDULCORANT TABLET AND A COMPRESSED EDULCORANT THUS OBTAINED |
| FR2841784A1 (en) * | 2002-07-08 | 2004-01-09 | Genfit S A | COMPOSITION BASED ON SUBSTITUTED 1,3-DIPHENYLPROP-2EN-1-ONE DERIVATIVES, PREPARATION AND USES |
| JP2004503503A (en) * | 2000-06-13 | 2004-02-05 | ラトガーズ，ザ ステイト ユニバーシティ | Hydroxylated chalcone compounds with antitumor activity extracted from licorice root |
| KR100564811B1 (en) * | 2004-11-17 | 2006-03-27 | 천승훈 | Licochalcone e and anticancer composition comprising the same |
| US7566737B2 (en) | 2002-07-08 | 2009-07-28 | Genfit | Combinations of substituted 1,3-diphenylprop-2-en-1-one derivatives with other therapeutically active ingredients |
| CN109966275A (en) * | 2017-12-11 | 2019-07-05 | 北京芳草园生物科技有限公司 | Quinoid chalcone compound application in preparation of anti-tumor drugs |
-
1992
- 1992-10-09 JP JP27205392A patent/JPH06122623A/en active Pending
Cited By (19)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7432303B2 (en) | 1999-12-23 | 2008-10-07 | J. Phillip Bowen | Chalcone and its analogs as agents for the inhibition of angiogenesis and related disease states |
| US6462075B1 (en) | 1999-12-23 | 2002-10-08 | The University Of Georgia Research Foundation, Inc. | Chalcone and its analogs as agents for the inhibition of angiogensis and related disease states |
| US7872029B2 (en) | 1999-12-23 | 2011-01-18 | Bowen J Phillip | Chalcone and its analogs as agents for the inhibition of angiogenesis and related disease states |
| WO2001046110A3 (en) * | 1999-12-23 | 2002-02-21 | Univ Georgia Res Found | Chalcone and its analogs as agents for the inhibition of angiogenesis and related disease states |
| US6906105B2 (en) | 1999-12-23 | 2005-06-14 | J. Phillip Bowen | Chalcone and its analogs as agents for the inhibition of angiogenesis and related disease states |
| JP2004503503A (en) * | 2000-06-13 | 2004-02-05 | ラトガーズ，ザ ステイト ユニバーシティ | Hydroxylated chalcone compounds with antitumor activity extracted from licorice root |
| FR2826549A1 (en) * | 2001-06-28 | 2003-01-03 | Roquette Freres | PROCESS FOR THE PREPARATION OF A COMPRESSED EDULCORANT TABLET AND A COMPRESSED EDULCORANT THUS OBTAINED |
| WO2003001925A3 (en) * | 2001-06-28 | 2003-04-17 | Roquette Freres | Method for preparing a sweetening tablet and resulting sweetening tablet |
| EA012699B1 (en) * | 2002-07-08 | 2009-12-30 | Женфит | Composition based on substituted 1,3-diphenylprop-2-en-1-one derivatives and use thereof |
| US7566737B2 (en) | 2002-07-08 | 2009-07-28 | Genfit | Combinations of substituted 1,3-diphenylprop-2-en-1-one derivatives with other therapeutically active ingredients |
| US7632870B2 (en) | 2002-07-08 | 2009-12-15 | Genfit | Composition based on substituted 1,3-diphenylprop-2-en-1-one derivatives, preparation and uses thereof |
| WO2004005243A3 (en) * | 2002-07-08 | 2004-04-22 | Genfit | Composition based on substituted 1,3-diphenylprop-2-en-1-one derivatives |
| FR2841784A1 (en) * | 2002-07-08 | 2004-01-09 | Genfit S A | COMPOSITION BASED ON SUBSTITUTED 1,3-DIPHENYLPROP-2EN-1-ONE DERIVATIVES, PREPARATION AND USES |
| US7943661B2 (en) | 2002-07-08 | 2011-05-17 | Genfit | Substituted 1,3-diphenylprop-2-en-1-one derivatives and preparation and uses thereof |
| US8058308B2 (en) | 2002-07-08 | 2011-11-15 | Genfit | Substituted 1,3-diphenylprop-2-en-1-one derivatives, preparation and uses thereof |
| US8106097B2 (en) | 2002-07-08 | 2012-01-31 | Genfit | Composition based on substituted 1,3-diphenylprop-2-en-1-one derivatives, preparation and uses thereof |
| KR100564811B1 (en) * | 2004-11-17 | 2006-03-27 | 천승훈 | Licochalcone e and anticancer composition comprising the same |
| CN109966275A (en) * | 2017-12-11 | 2019-07-05 | 北京芳草园生物科技有限公司 | Quinoid chalcone compound application in preparation of anti-tumor drugs |
| CN109966275B (en) * | 2017-12-11 | 2021-11-30 | 谷冲医药(北京)股份有限公司 | Application of quinoid chalcone compound in preparation of antitumor drugs |
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