JPS63215629A - Antistress ulcer agent - Google Patents
Antistress ulcer agentInfo
- Publication number
- JPS63215629A JPS63215629A JP62049143A JP4914387A JPS63215629A JP S63215629 A JPS63215629 A JP S63215629A JP 62049143 A JP62049143 A JP 62049143A JP 4914387 A JP4914387 A JP 4914387A JP S63215629 A JPS63215629 A JP S63215629A
- Authority
- JP
- Japan
- Prior art keywords
- alkenylsalicylic
- formula
- acid
- leaves
- antistress
- 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.)
- Granted
Links
- 230000002180 anti-stress Effects 0.000 title claims abstract description 7
- 208000025865 Ulcer Diseases 0.000 title abstract description 6
- 231100000397 ulcer Toxicity 0.000 title abstract description 6
- 239000002253 acid Substances 0.000 claims abstract description 11
- 125000003342 alkenyl group Chemical group 0.000 claims abstract description 4
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 3
- 206010042220 Stress ulcer Diseases 0.000 claims description 9
- 208000000718 duodenal ulcer Diseases 0.000 claims description 9
- 239000000126 substance Substances 0.000 claims description 2
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 abstract description 6
- 150000001875 compounds Chemical class 0.000 abstract description 6
- 239000003814 drug Substances 0.000 abstract description 4
- 239000007788 liquid Substances 0.000 abstract description 4
- 235000008100 Ginkgo biloba Nutrition 0.000 abstract description 3
- 239000007787 solid Substances 0.000 abstract description 3
- 230000007059 acute toxicity Effects 0.000 abstract description 2
- 231100000403 acute toxicity Toxicity 0.000 abstract description 2
- 239000002775 capsule Substances 0.000 abstract description 2
- 239000008187 granular material Substances 0.000 abstract description 2
- 239000000203 mixture Substances 0.000 abstract description 2
- 230000002265 prevention Effects 0.000 abstract description 2
- 239000006188 syrup Substances 0.000 abstract description 2
- 235000020357 syrup Nutrition 0.000 abstract description 2
- 235000011201 Ginkgo Nutrition 0.000 abstract 1
- 241000218628 Ginkgo Species 0.000 abstract 1
- 238000007796 conventional method Methods 0.000 abstract 1
- 238000009472 formulation Methods 0.000 abstract 1
- 239000002075 main ingredient Substances 0.000 abstract 1
- 230000000694 effects Effects 0.000 description 5
- 238000002360 preparation method Methods 0.000 description 4
- 241000700159 Rattus Species 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 2
- 244000194101 Ginkgo biloba Species 0.000 description 2
- 238000002451 electron ionisation mass spectrometry Methods 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 239000012046 mixed solvent Substances 0.000 description 2
- 230000000704 physical effect Effects 0.000 description 2
- 238000010898 silica gel chromatography Methods 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 210000001015 abdomen Anatomy 0.000 description 1
- 230000000895 acaricidal effect Effects 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- ZPEIMTDSQAKGNT-UHFFFAOYSA-N chlorpromazine Chemical compound C1=C(Cl)C=C2N(CCCN(C)C)C3=CC=CC=C3SC2=C1 ZPEIMTDSQAKGNT-UHFFFAOYSA-N 0.000 description 1
- 229960001076 chlorpromazine Drugs 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- ZKQFHRVKCYFVCN-UHFFFAOYSA-N ethoxyethane;hexane Chemical compound CCOCC.CCCCCC ZKQFHRVKCYFVCN-UHFFFAOYSA-N 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 238000005194 fractionation Methods 0.000 description 1
- 210000004907 gland Anatomy 0.000 description 1
- 239000002035 hexane extract Substances 0.000 description 1
- 238000007654 immersion Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- GBMDVOWEEQVZKZ-UHFFFAOYSA-N methanol;hydrate Chemical compound O.OC GBMDVOWEEQVZKZ-UHFFFAOYSA-N 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 239000002831 pharmacologic agent Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- -1 troches Substances 0.000 description 1
- 208000037911 visceral disease Diseases 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Plant Substances (AREA)
Abstract
Description
【発明の詳細な説明】
〔産業上の利用分野〕
本発明はストレスに起因する潰瘍の予防並びに治療に用
いられ・る薬剤に関する。DETAILED DESCRIPTION OF THE INVENTION [Field of Industrial Application] The present invention relates to a drug used for the prevention and treatment of ulcers caused by stress.
一般式〔Ｉ〕で表される６−アルケニルサリチル酸はイ
チョウ（Ｇｉｎｋｐｏ ｂｉｌｏｂａ Ｌ、 ）の葉
等に多く含まれる化合物であり、その構造は、アナリテ
ィカル・ケミストリイ（Ａｎａｌ、 ｃｈｅｗ、）。6-Alkenylsalicylic acid represented by the general formula [I] is a compound that is abundantly contained in leaves of Ginkgo biloba (Ginkpo biloba L.), and its structure is similar to that of Analytical Chemistry (Anal, Chew, ).
並、 ７３９ （１９６８）に報告されている。It is reported in Parallel, 739 (1968).
また、上記化合物は抗菌作用〔特開昭５６−８３４１６
号公報〕、殺ダニ作用〔ジャーナル・オブ・ケミカル・
エコロジイ（Ｊ、Ｃｈｅｍ、Ｅｃｏｌ、） 。In addition, the above compound has antibacterial activity [JP-A-56-83416
No. Publication], Acaricidal Effect [Journal of Chemical
Ecology (J, Chem, Ecol,).
則、 ７１３ （１９８４）） 、抗腫瘍作用〔日本生
薬学会第３３回年会講演要旨集Ｐ２Ｂ （１９８６）３
等の生理作用を示すことが知られている。Regulations, 713 (1984)), Antitumor Effect [Collection of Abstracts of the 33rd Annual Meeting of the Japanese Society of Herbal Pharmaceutical Sciences P2B (1986) 3
It is known to exhibit physiological effects such as
しかしながら、内臓疾患に対する薬理効果は明らかにさ
れていない。However, its pharmacological effects on visceral diseases have not been clarified.
一方、ストレス潰瘍に効果を示す化合物は数多く知られ
ているが、本発明の６−アルケニルサリチル酸に抗スト
レス潰瘍作用が認められたという報告はない。On the other hand, although many compounds are known that are effective against stress ulcers, there is no report that the 6-alkenylsalicylic acid of the present invention has an anti-stress ulcer effect.
本発明者等はイチョウ葉中に含まれる薬理活性成分を明
らかにする目的で研究を進める中で、２種の６−アルケ
ニルサリチル酸が抗ストレス潰瘍活性を有することを見
出し本発明を完成するに至った。While proceeding with research aimed at elucidating the pharmacologically active ingredients contained in ginkgo biloba, the present inventors discovered that two types of 6-alkenylsalicylic acids have anti-stress ulcer activity, leading to the completion of the present invention. Ta.
即ち、本発明は一般式〔Ｉ〕で表される６−アルケニル
サリチル酸を含有してなる抗ストレス潰瘍剤である。That is, the present invention is an anti-stress ulcer agent containing 6-alkenylsalicylic acid represented by general formula [I].
Ｈ
（式中、ＲはＣｌ５Ｈ１９又はＣｌＪ１３の直鎖アルケ
ニル基を示す。）
本発明の抗ストレス潰瘍剤の主成分である６−アルケニ
ルサリチル酸は、例えばイチョウ（且兆Ｂ３ ｂｉｌ
ｏｂａ Ｌ、 ）の葉をメタノールで抽出し、得られる
抽出液をヘキサンで分配抽出し、ヘキサン抽出物をシリ
カゲルカラムクロマトグラフィーに付し、ヘキサン−エ
ーテルの混合溶媒で溶出してくるフラクシヨンより得る
ことが出来る。H (wherein, R represents a straight chain alkenyl group of Cl5H19 or ClJ13).
Oba L.) leaves are extracted with methanol, the resulting extract is partitioned and extracted with hexane, the hexane extract is subjected to silica gel column chromatography, and the fraction is obtained from the fraction eluted with a mixed solvent of hexane-ether. I can do it.
このようにして得られる６−アルケニルサリチル酸は側
鎖のアルケニル基がＣｌ５Ｈ！９のもの（以下（１−ａ
）と記す）とＣｌ４３３のもの（以下（１−ｂ）と記す
）の混合物であるが、これらを更に逆相のシリカゲルカ
ラムクロマトグラフィーに付し、水−メタノール（５：
９５）の混合溶媒で溶出分画すれば単一成分に分離、精
製することができる。In the 6-alkenylsalicylic acid obtained in this way, the alkenyl group in the side chain is Cl5H! 9 (hereinafter (1-a)
)) and Cl433 (hereinafter referred to as (1-b)), these were further subjected to reverse phase silica gel column chromatography, and water-methanol (5:
It can be separated and purified into single components by elution and fractionation with a mixed solvent of 95).
（１−ａ）の主な物性値を以下に示す。The main physical property values of (1-a) are shown below.
分子式： ＣｚｔｌｂｎＯ＋
ＥＩ−ＭＳ ： ｍ／ Ｚ ３４６（Ｍ”）’ＨＮＭＲ
（ＣＤＣＩり ：δ１０．９７（ＩＨ，ｂｒｓ） 、
７．３６（ＩＨ。Molecular formula: CztlbnO+ EI-MS: m/Z 346(M”)'HNMR
(CDCI: δ10.97 (IH, brs),
7.36 (IH.
ｔ、Ｊ−８，５）、６．８７（ｉｎ、ａｄ、Ｊ・８．５
．１．２）、６．７７（ＩＨ，ｄｄ、、ｒ−８，５，１
，２） 、５．３４（２Ｈ，ｔ。t, J-8,5), 6.87 (in, ad, J・8.5
．． 1.2), 6.77 (IH, dd,, r-8,5,1
, 2) , 5.34 (2H, t.
Ｊ＝４．５）、２．９８（２■、ｔ、Ｊ＝７．３）、２
．０１（４Ｈ。J=4.5), 2.98 (2■, t, J=7.3), 2
．． 01 (4H.
ｏ＋）、１．６０（２Ｈ，ｍ）、１．２９（１７Ｈ，ｍ
） 、０．８９（３Ｂ、 ｔ、 Ｊ＝６．９） ｐｐｎ
＋”ＣＮＭＲ（ＣＤＣＩｓ） ：δ１７５．３．１６３
．２．１４７．３．１３５．０．１２９．６．１２９．
５．１２２．４．１１５．６．１１０．１．３６．４．
３１．９．２９．７．２９．６．２９．５．２９．４．
２９．３．２９．２．２７．１．２６．９．２２．３．
１４．０ ｐｐｍ（Ｉ−ｂ）の主な物性値を以下に示す
。o+), 1.60 (2H, m), 1.29 (17H, m
), 0.89 (3B, t, J=6.9) ppn
+”CNMR (CDCIs): δ175.3.163
．． 2.147.3.135.0.129.6.129.
5.122.4.115.6.110.1.36.4.
31.9.29.7.29.6.29.5.29.4.
29.3.29.2.27.1.26.9.22.3.
The main physical property values of 14.0 ppm (I-b) are shown below.
分子式： ＣｚＪ！ｓＯ＋
ＥＩ−ＭＳ ： ｍ／ Ｚ ３７４（Ｍ”）’ＨＮＭ
Ｒ（ＣＤＣＩり ：６１０．９６（ＩＨ，ｂｒｓ）
、７．３６（ＩＨ。Molecular formula: CzJ! sO+ EI-MS: m/Z 374(M”)'HNM
R (CDCI: 610.96 (IH, brs)
, 7.36 (IH.
ｔ、Ｊ・８．５）、６．８７（ＩＨ，ｄｄ、Ｊ−８，５
，１，２） 、６．７７（ＬＨ，ｄｄ、Ｊ・８．５．
１．２） 、５．３４（２Ｈ，ｔ。t, J-8.5), 6.87 (IH, dd, J-8,5
, 1, 2), 6.77 (LH, dd, J・8.5.
1.2), 5.34 (2H, t.
Ｊ＝４．５）、２．９８（２Ｈ，ｔ、 Ｊ−７，３）、
２．０２（４Ｂ。J=4.5), 2.98 (2H,t, J-7,3),
2.02 (4B.
ｍ）、１．６１（２Ｈ，ｍ）、１．２７（２１１１，ｍ
） 、０．８９（３Ｈ，ｔ、 Ｊ、６．９） ｐｐｍ
”ＣＮＭＲ（ＣＤＣｈ） ：δ１７５．８．１６３．１
．１４７．４．１３５．１．１２９．５．１２９．４．
１２２．４．１１５．６．１１０．１．３６．４．３１
．９．２９．７．２９．６．２９．５．２９．４．２９
．３．２７．２．２６．９．２２．３．１４．０ ｐｐ
ｎ＋
〔実施例〕
次に一般式〔Ｉ〕で表わされる６−アルケニルサリチル
酸のストレス潰瘍に対する作用について実施例により説
明する。m), 1.61 (2H, m), 1.27 (2111, m
), 0.89 (3H, t, J, 6.9) ppm "CNMR (CDCh): δ175.8.163.1
．． 147.4.135.1.129.5.129.4.
122.4.115.6.110.1.36.4.31
．． 9.29.7.29.6.29.5.29.4.29
．． 3.27.2.26.9.22.3.14.0pp
n+ [Example] Next, the effect of 6-alkenylsalicylic acid represented by general formula [I] on stress ulcers will be explained using examples.
実施例１
２４時間絶食後の雄性ラットに被験薬物として、Ｔｗｅ
ｅｎ８０の０．５％水溶液に（１−ｂ）を懸濁した液を
経口投与し、３０分後にこのラットを金網によって拘束
し、２５℃の水に胸部まで水浸した。Example 1 Twe was administered as a test drug to male rats after 24-hour fasting.
A suspension of (1-b) in a 0.5% aqueous solution of en80 was orally administered, and 30 minutes later, the rat was restrained with a wire mesh and immersed up to the chest in water at 25°C.
１６時間後、ラットを開腹して胃を摘出し１％ホルマリ
ンで固定した後これを切開し腺背部の損傷の長径の和を
潰瘍指数とした。After 16 hours, the abdomen of the rat was opened, the stomach was removed, fixed with 1% formalin, and then incised, and the sum of the long diameters of the lesions on the back of the gland was defined as the ulcer index.
（１−ｂ）の対照群に対する潰瘍発生抑制率は２５及び
５０＋＋＋ｇ／ｋｇの経口投与でそれぞれ４７．７１％
であり有意な抑制効果を示した。対照薬として用いたク
ロルプロマジンの抑制率は２０ａ＋ｇ／ｋｇの経口投与
で６３％であった。The ulcer incidence inhibition rate of (1-b) compared to the control group was 47.71% for oral administration of 25 and 50+++g/kg, respectively.
showed a significant inhibitory effect. The inhibition rate of chlorpromazine used as a control drug was 63% when administered orally at 20a+g/kg.
実施例２
実施例１と同じ拘束水浸ストレス潰瘍法を用い、化合物
ＣＩ−ａ）の抑制効果を調べた。１０及び３０ｍｇ／ｋ
ｇでの抑制率はそれぞれ２８．５４％であった。Example 2 Using the same restrained water immersion stress ulcer method as in Example 1, the inhibitory effect of compound CI-a) was investigated. 10 and 30mg/k
The inhibition rate in g was 28.54%, respectively.
以上のように本発明の６−アルケニルサリチル酸は優れ
た抗ストレス潰瘍作用を示すことが認められた。As described above, the 6-alkenylsalicylic acid of the present invention was found to exhibit excellent anti-stress ulcer effects.
また２００ｍｇ／ｋｇの腹腔内投与及び３００＋ｗｇ／
ｋｇの経口投与での死亡例はなく、急性毒性は低いと考
えられる。Also, 200 mg/kg intraperitoneal administration and 300+wg/
There were no cases of death following oral administration of 1 kg, and acute toxicity is considered to be low.
従って、本発明の６−アルケニルサリチル酸はその有効
且つ非毒性量を含有する組成物の形で、ストレス潰瘍の
予防または改善を目的とする医薬品として用いることが
出来、例えば経口剤としては、錠剤、カプセル剤、トロ
ーチ剤、顆粒剤、散剤等の固体製剤あるいは水剤、シロ
ップ剤等の液剤として用いることが出来る。そしてこれ
ら各種の製剤は慣用の無機又は存機の、或いは固体又は
液体の医薬製剤用担体を用いて公知の方法で製造するこ
とができる。Therefore, the 6-alkenylsalicylic acid of the present invention can be used in the form of a composition containing an effective and non-toxic amount as a pharmaceutical for the purpose of preventing or improving stress ulcers. For example, as an oral preparation, tablets, It can be used as solid preparations such as capsules, troches, granules, and powders, or liquid preparations such as solutions and syrups. These various preparations can be manufactured by known methods using conventional inorganic, organic, solid, or liquid carriers for pharmaceutical preparations.
Claims (1)
含有してなる抗ストレス潰瘍剤。 ▲数式、化学式、表等があります▼（ I ） （式中、ＲはＣ＿１＿５Ｈ＿２＿９、又はＣ＿１＿７Ｈ
＿３＿３の直鎖アルケニル基を示す。）[Scope of Claims] An anti-stress ulcer agent containing 6-alkenylsalicylic acid represented by the general formula [I]. ▲There are mathematical formulas, chemical formulas, tables, etc.▼ (I) (In the formula, R is C_1_5H_2_9 or C_1_7H
_3_3 shows a straight chain alkenyl group. )
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP62049143A JPH0788306B2 (en) | 1987-03-04 | 1987-03-04 | Anti-stress ulcer agent |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP62049143A JPH0788306B2 (en) | 1987-03-04 | 1987-03-04 | Anti-stress ulcer agent |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS63215629A true JPS63215629A (en) | 1988-09-08 |
| JPH0788306B2 JPH0788306B2 (en) | 1995-09-27 |
Family
ID=12822864
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP62049143A Expired - Lifetime JPH0788306B2 (en) | 1987-03-04 | 1987-03-04 | Anti-stress ulcer agent |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH0788306B2 (en) |
-
1987
- 1987-03-04 JP JP62049143A patent/JPH0788306B2/en not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| JPH0788306B2 (en) | 1995-09-27 |
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