JPS60199815A - Pharmaceutical containing gallic acid derivative - Google Patents
Pharmaceutical containing gallic acid derivativeInfo
- Publication number
- JPS60199815A JPS60199815A JP5598484A JP5598484A JPS60199815A JP S60199815 A JPS60199815 A JP S60199815A JP 5598484 A JP5598484 A JP 5598484A JP 5598484 A JP5598484 A JP 5598484A JP S60199815 A JPS60199815 A JP S60199815A
- Authority
- JP
- Japan
- Prior art keywords
- gallic acid
- acid derivative
- present
- pharmaceutical
- pharmaceutical containing
- 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
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- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
Description
【発明の詳細な説明】
本発明は没食子酸誘導体を含有する血小板凝集抑制剤お
よび抗アレルギー剤に関する。DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a platelet aggregation inhibitor and an antiallergic agent containing gallic acid derivatives.
本発明者はかねてよりインドネシア産植物ｐｈｙ−１１
ａｎｔｈｕｓ ｎ１ｒｕｒｉ Ｌからの抽出物の医薬へ
の応用について種々の検討をおこなってきたが、その−
成分である没食子酸エチルに特殊な医薬活性があること
を知った。そこで、さらに他の没食子酸誘導体の医薬活
性について検討をおこなったところ、著しい血小板凝集
抑制作用および抗アレルギー作用のあることを知り本発
明を完成するに至った。The present inventor has been working on the Indonesian plant phy-11 for some time.
Various studies have been conducted on the application of extracts from anthus n1ruri L to medicine, but the
I learned that the ingredient ethyl gallate has special medicinal activity. Therefore, when we further investigated the medicinal activity of other gallic acid derivatives, we found that they have a remarkable platelet aggregation inhibiting effect and antiallergic effect, leading to the completion of the present invention.
すなわち本発明の目的は特定の没食子酸誘導体を含有す
る血小板凝集抑制剤および抗アレルギー剤の提供である
。That is, an object of the present invention is to provide a platelet aggregation inhibitor and an antiallergic agent containing a specific gallic acid derivative.
以下に本発明を説明する。The present invention will be explained below.
本発明に係る物質は式
（式中、Ｒは一〇、Ｈ，、−ｎ−Ｃ４Ｈｇ 、 −ｎ−
Ｃ６Ｈ１，。The substance according to the present invention has the formula (wherein R is 10, H,, -n-C4Hg, -n-
C6H1,.
−ｎ−Ｃ８Ｈ１７，−ｎ−Ｃ，ｏＨ２，、−ｎ−ＣＩ２
Ｈ２１−ｎ−Ｃ，、Ｈ２ｇ。-n-C8H17, -n-C,oH2,, -n-CI2
H21-n-C,, H2g.
を表わす）
によって示される没食子酸誘導体である。これらの物質
は、従来公知の物質であり、各物質については、下記に
列挙する文献（１）〜１１０の記述が９本発明における
説明として引用される。is a gallic acid derivative represented by These substances are conventionally known substances, and for each substance, the descriptions in Documents (1) to 110 listed below are cited as explanations in the present invention.
（１） Ｈ，Ｃ，Ｂｉｄｄｌｅ；Ｊ、Ａ、Ｃ，Ｓ、 ３
５９６（２） Ｗ、 Ｇ、 Ｃｈｒｉｓｔｉａｎｓｅｎ
； Ｊ、Ａ、Ｃ，Ｓ、 ４８１３５８〜６５（１９２
６）（３） Ｓ、Ｇ、Ｍｏｒｒｉｓｅｔａｌ；Ｊ、Ａ、
Ｃ，８，６８５００〜１（１９４６）（４） Ｓ、Ｇ、
Ｍｏｒｒｉｓｅｔａｌ；Ｊ、Ａ、Ｃ，Ｓ、６８５００〜
１（１９４６）（５） Ｋ、Ｊ、Ｈ，ｖａｎＳｌｕｉｓ
；ＦｏｏｄＭａｎｕｆ、２６９９〜１０１（１９５１）
（６） Ｋ、Ｊ、Ｈ，ｖａｎＳｌｕｉｓ；ＦｏｏｄＭａ
ｎｕｆ、２６９９〜１０１（１９５１）（７） Ｓ、Ｇ
、 Ｍｏｒｒｉｓ ｅｔ ａｌ ； Ｊ、Ａ、Ｃ，Ｓ、
６８５００〜１ （１９４６）（８） Ｓ、Ｇ、Ｍｏ
ｒｒｉｓｅｔａｌ；Ｊ、Ａ、Ｃ，Ｓ、６８５００〜１（
１９４６）（９） Ｓ、Ｇ、Ｍｏｒｒｉｓｅｔａｌ；Ｊ
、Ａ、Ｃ，５６８５００〜１（１９４６）（１０） Ｊ
ａｐａｎＫｏｋａｉ ７５２３，４０５本発明に係る物
質は後記実験例によって示されるごとく血小板凝集抑制
作用を有する。従って。(1) H, C, Biddle; J, A, C, S, 3
596(2) W, G, Christiansen
; J, A, C, S, 481358-65 (192
6) (3) S, G, Morrisetal; J, A,
C, 8, 68500-1 (1946) (4) S, G.
Morrisetal; J, A, C, S, 68500~
1 (1946) (5) K, J, H, vanSluis
; Food Manuf, 2699-101 (1951)
(6) K, J, H, vanSluis; FoodMa
nuf, 2699-101 (1951) (7) S, G
, Morris et al; J.A.C.S.
68500-1 (1946) (8) S, G, Mo
rrisetal; J, A, C, S, 68500-1 (
1946) (9) S, G, Morrisetal; J
, A, C, 568500-1 (1946) (10) J
apanKokai 7523,405 The substance according to the present invention has a platelet aggregation inhibiting effect as shown by the experimental examples described later. Therefore.
本発明物質は血小板凝集抑制剤として脳梗塞、−過性脳
虚血発作、心筋硬塞、狭心症、末梢動脈閉塞症９人工透
析において使用される。また本発明物質は後記実験例に
おいて５−リポキシゲナーゼ阻害作用を有することが判
明し、従って抗アレルギー剤として喘息、炎症において
使用される。The substance of the present invention is used as a platelet aggregation inhibitor in cerebral infarction, hyperischemic attack, myocardial infarction, angina pectoris, and peripheral arterial occlusion 9 artificial dialysis. Furthermore, the substance of the present invention was found to have a 5-lipoxygenase inhibitory effect in the experimental examples described later, and therefore is used as an antiallergic agent in asthma and inflammation.
本発明血小板凝集抑制剤および本発明抗アレルギー剤は
経口投与される。経口投与を便ならしめるための適当な
賦形剤１例えば乳糖、デンプン。The platelet aggregation inhibitor of the present invention and the antiallergic agent of the present invention are orally administered. Suitable excipients for fecalizing oral administration, such as lactose, starch.
ヒドロキシプロピルセルロース、カルボキンメチルセル
ロース、タルク、ステアリン酸カルシウム等は自由に選
択すればよく１本発明を限定するものではない。Hydroxypropylcellulose, carboquine methylcellulose, talc, calcium stearate, etc. may be freely selected and do not limit the present invention.
経口用量は例えば１日０．０５〜１．Ｏｇが適当である
。Oral dosage is, for example, 0.05-1. Og is suitable.
また本発明物質はマウスにおいてｐ、ｏ ３００ ｍｇ
７ｋｇで毒性が現われない。In addition, the substance of the present invention has a p,o concentration of 300 mg in mice.
Toxicity does not appear at 7kg.
以下の実験例によって本発明に係る物質の医薬効果につ
いて説明する。The following experimental examples will explain the medicinal effects of the substances according to the present invention.
実験例１ 試料と方法 試料として本発明に係る没食子酸誘導体をとりあげた。Experimental example 1 Samples and methods A gallic acid derivative according to the present invention was taken as a sample.
雄性家兎（白色在来種１体重２．５〜３ ｋｙ ）の耳
静脈あるいは頚動脈から、 ３．１３％クエン酸ナトリ
ウム入り、ポリエチレン製注射器で採血をした。採取し
た血液を２００Ｘ＆、 １５分間の遠心により、血小板
浮遊面１ｉ（ＰＲＰ）を分取した。Blood was collected from the ear vein or carotid artery of male domestic rabbits (white native breed, weight 2.5-3 ky) using a polyethylene syringe containing 3.13% sodium citrate. The collected blood was centrifuged at 200X for 15 minutes to collect platelet floating surface 1i (PRP).
試料を２００μｉ ／Ｉｎｅの濃度になるように生理食
塩水または０．１％ＤＭＳＯ含有生理食塩水に溶解し、
そ（Ｄ２５ｐｅをＰＲＰｏ、２ ｌ ニ加え、３７℃、
３分間インキュベー） Ｌ、、１．５ｍＭアラキドン酸
２５μｌ添加し。Dissolve the sample in physiological saline or physiological saline containing 0.1% DMSO to a concentration of 200μi/Ine,
(Add D25pe to PRPo, 2 l, 37℃,
Incubate for 3 minutes) Add 25 μl of 1.5 mM arachidonic acid.
凝集を惹起した。凝集は、 Ｂｏｒｎの比濁法にもとづ
き、 ａｇｇｒｅｇｏｍｅｔθｒで測定した。（アラキ
ドン酸終濃度１５０μＭ、試料終濃度２０μＭ）試料の
凝集抑制効果は、試料を含有しないとき（コントロール
）の凝集抑制率を０％とし、コントロールに対する抑制
率で判定した。caused aggregation. Aggregation was measured using an aggregomet θr based on Born's turbidimetry. (Arachidonic acid final concentration 150 μM, sample final concentration 20 μM) The aggregation inhibition effect of the sample was determined by the inhibition rate relative to the control, with the aggregation inhibition rate when no sample was contained (control) being 0%.
結果
結果を表１に示す。表１は、アラキドン酸０度１５０μ
Ｍにおける試料２０μＭでの血小板凝集抑制効果を示す
。表１より９本発明に係る物質は、没食子酸プロピルに
比較して強い血小板凝集抑制効果を有することが判明す
る。Results The results are shown in Table 1. Table 1 shows arachidonic acid 0 degrees 150μ
The figure shows the platelet aggregation inhibitory effect of a sample of 20 μM in M. Table 1 shows that the substance according to the present invention has a stronger platelet aggregation inhibiting effect than propyl gallate.
実験例２ 試料と方法 試料として本発明に係る没食子酸誘導体をとりあげた。Experimental example 2 Samples and methods A gallic acid derivative according to the present invention was taken as a sample.
１ ｒｎＭ−ＥＤＴＡ 、 ２ ｍＭ ＧＳＨ、２５０
ｍＭ−８ｕｃｒｏｓｅを含有する５０ ｍＭ リン酸緩
衝液（ＰＨ７，４）に、ラット好塩基性白血病細胞（Ｒ
ＢＬ−１）をｌＸｌ０’個／ｍｌとなるよう懸濁した。1 rnM-EDTA, 2mM GSH, 250
Rat basophil leukemia cells (R
BL-1) was suspended at lXl0' cells/ml.
この懸濁液を水冷化、超音波処理（２０Ｗ、１０秒、５
回）シ、細胞破砕液を得た。This suspension was water-cooled and ultrasonicated (20W, 10 seconds, 5
2) A cell lysate was obtained.
細胞破砕液０．５ ｍｌに試料、アラキドン酸、塩化カ
ルシウム溶液を加え、３７℃、５分間反応させた（試料
；０，１μＭ、１μＭ、１０μＭ、アラキドン酸； ２
００μＭ、塩化カルシウム； ２ｍＭ）。A sample, arachidonic acid, and a calcium chloride solution were added to 0.5 ml of the cell disruption solution, and the mixture was reacted at 37°C for 5 minutes (sample; 0.1 μM, 1 μM, 10 μM, arachidonic acid; 2
00 μM, calcium chloride; 2 mM).
飽和食塩溶液２００μ６．２Ｎ−ギ酸溶液５０μｌを加
工、クロロホルム／メタノール混ｉ（４：１．／ｖ）２
００μｌで抽出した。その５０μｅをシリカゲル薄層板
にスポットし、ジエチルエーテル／石油エーテル／酢酸
（８５： １５ ： ０．１． Ｖ／ｖ）で展開した。Process 200 μl of saturated salt solution 6.2N-50 μl of formic acid solution, mix chloroform/methanol (4:1./v) 2
Extracted with 00 μl. 50 μe thereof was spotted on a thin silica gel plate and developed with diethyl ether/petroleum ether/acetic acid (85:15:0.1. V/v).
オートラジオグラフィーにより、５−ＨＥＴＥのスポッ
トを確認した後、相当する部分をかきとり。After confirming the 5-HETE spot by autoradiography, the corresponding area was scraped off.
液体シンチレーションカウンターでカウントした。Counts were performed using a liquid scintillation counter.
５−ＨＥＴＥ生成阻害率（５−リポキシゲナーゼ阻害率
）は、以下の式により算出した。The 5-HETE production inhibition rate (5-lipoxygenase inhibition rate) was calculated using the following formula.
なお、５−ＨＥＴＥおよび５−ＨＥＴＥ生成阻害率（５
−リポキシゲナーゼ阻害率）については、下記文献の記
述が説明として参照される。In addition, 5-HETE and 5-HETE production inhibition rate (5
- lipoxygenase inhibition rate), the descriptions in the following documents are referred to for explanation.
「プロスタグランディンの生化学」室田誠逸編東京化学
問人 Ｐ、２０〜２４ ・ Ｐ、９９〜１１４結果
結果を表２に示す。表２は、試料ｏ、ｉμＭ、１μＭ。"Biochemistry of Prostaglandins" Edited by Seiichi Murota, Tokyo Kagakujin, P, 20-24, P, 99-114 Results The results are shown in Table 2. Table 2 shows samples o, iμM, and 1μM.
１０μＭにおける５ −ＨＥＴＥ産生抑制効果を示す。The effect of suppressing 5-HETE production at 10 μM is shown.
表２より９本発明に係る物質は、 ＢＷ７５５Ｇに比較
して強い抗５−リポキシゲナーゼ活性を有することが判
明する。From Table 2, it is found that the 9 substances according to the present invention have stronger anti-5-lipoxygenase activity than BW755G.
表２
以下に記載する実施例をもって本発明をさらに具体的に
説明する。Table 2 The present invention will be explained in more detail with reference to the following examples.
実施例 １
没食子酸ｎ−デシルエステル１００．９ 、微結晶セル
ロース５０ｇ、）ウモロコシデンプン５０１９ ヲ混合
し、常法により散剤となし１本発明血小板凝集抑制剤と
する。Example 1 100.9 g of gallic acid n-decyl ester, 50 g of microcrystalline cellulose, and 5019 g of corn starch were mixed and prepared into a powder by a conventional method to prepare a platelet aggregation inhibitor of the present invention.
実施例２
没食子酸ｎ−ラウリルエステル１００ ｇ、乳糖１ｏｏ
ｙ、結晶セルロース９９＆、ＣＭＣカルシウム６０９を
混合し１次にステアリン酸カルシウム１ｇを８０メツシ
ユ篩を通して均等に混和し、打錠して１錠当り１８０
ｍｙの錠剤となし１本発明抗アレルギー剤とする。Example 2 Gallic acid n-lauryl ester 100 g, lactose 1oo
y, crystalline cellulose 99 & CMC calcium 609 are mixed, firstly 1 g of calcium stearate is mixed evenly through an 80 mesh sieve, and tableted to give 180 g of calcium stearate per tablet.
My tablet and pear 1 are used as the antiallergic agent of the present invention.
特許出願人 工−ザイ株式会社patent applicant Ko-zai Co., Ltd.
Claims (1)
６Ｈ，、。 −ｎ−０８Ｈ，、、−ｎ−ＣＩＪＩ２１ 、−ｎ−Ｃ，
２Ｈ２，、−ｎ−Ｃ：、、Ｈ２，。 を表わず） によって示される没食子酸誘導体を薬効成分として含有
する血小板凝集抑制剤 （２、特許請求の範囲第一項記載の没食子酸誘導体を薬
効成分として含有する抗アレルギー剤(1) Formula (wherein R is -CJi, -n-C4H,, -n-C
6H,. -n-08H,, -n-CIJI21, -n-C,
2H2,,-n-C:,,H2,. A platelet aggregation inhibitor containing a gallic acid derivative as a medicinal ingredient (2. An anti-allergic agent containing a gallic acid derivative as set forth in claim 1 as a medicinal ingredient)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP5598484A JPS60199815A (en) | 1984-03-26 | 1984-03-26 | Pharmaceutical containing gallic acid derivative |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP5598484A JPS60199815A (en) | 1984-03-26 | 1984-03-26 | Pharmaceutical containing gallic acid derivative |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPS60199815A true JPS60199815A (en) | 1985-10-09 |
Family
ID=13014344
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP5598484A Pending JPS60199815A (en) | 1984-03-26 | 1984-03-26 | Pharmaceutical containing gallic acid derivative |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS60199815A (en) |
-
1984
- 1984-03-26 JP JP5598484A patent/JPS60199815A/en active Pending
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