JPH04360829A - Antiulcer agent containing 3-phenylpropenal derivative as active ingredient - Google Patents
Antiulcer agent containing 3-phenylpropenal derivative as active ingredientInfo
- Publication number
- JPH04360829A JPH04360829A JP3136460A JP13646091A JPH04360829A JP H04360829 A JPH04360829 A JP H04360829A JP 3136460 A JP3136460 A JP 3136460A JP 13646091 A JP13646091 A JP 13646091A JP H04360829 A JPH04360829 A JP H04360829A
- Authority
- JP
- Japan
- Prior art keywords
- active ingredient
- ulcer
- antiulcer agent
- methoxycinnamaldehyde
- agent 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.)
- Granted
Links
- 239000003699 antiulcer agent Substances 0.000 title claims abstract description 13
- 239000004480 active ingredient Substances 0.000 title claims abstract description 12
- KJPRLNWUNMBNBZ-QPJJXVBHSA-N (E)-cinnamaldehyde Chemical class O=C\C=C\C1=CC=CC=C1 KJPRLNWUNMBNBZ-QPJJXVBHSA-N 0.000 title description 3
- KKVZAVRSVHUSPL-UHFFFAOYSA-N o-methoxycinnamic aldehyde Natural products COC1=CC=CC=C1C=CC=O KKVZAVRSVHUSPL-UHFFFAOYSA-N 0.000 claims description 19
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 abstract description 20
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 abstract description 8
- 208000025865 Ulcer Diseases 0.000 abstract description 8
- 231100000397 ulcer Toxicity 0.000 abstract description 8
- -1 alkyl ketone Chemical class 0.000 abstract description 7
- 238000000605 extraction Methods 0.000 abstract description 5
- 241001465754 Metazoa Species 0.000 abstract description 4
- 150000001875 compounds Chemical class 0.000 abstract description 4
- 239000000284 extract Substances 0.000 abstract description 4
- 239000003960 organic solvent Substances 0.000 abstract description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 abstract description 3
- 235000014113 dietary fatty acids Nutrition 0.000 abstract description 3
- 239000000194 fatty acid Substances 0.000 abstract description 3
- 229930195729 fatty acid Natural products 0.000 abstract description 3
- 208000008469 Peptic Ulcer Diseases 0.000 abstract description 2
- 239000003463 adsorbent Substances 0.000 abstract description 2
- 125000001931 aliphatic group Chemical group 0.000 abstract description 2
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 abstract description 2
- 239000012141 concentrate Substances 0.000 abstract description 2
- 239000000741 silica gel Substances 0.000 abstract description 2
- 229910002027 silica gel Inorganic materials 0.000 abstract description 2
- 238000001256 steam distillation Methods 0.000 abstract description 2
- HGINCPLSRVDWNT-UHFFFAOYSA-N Acrolein Chemical compound C=CC=O HGINCPLSRVDWNT-UHFFFAOYSA-N 0.000 abstract 2
- 239000008989 cinnamomi cortex Substances 0.000 abstract 2
- 208000011906 peptic ulcer disease Diseases 0.000 abstract 1
- KKVZAVRSVHUSPL-GQCTYLIASA-N Cassiastearoptene Chemical compound COC1=CC=CC=C1\C=C\C=O KKVZAVRSVHUSPL-GQCTYLIASA-N 0.000 description 15
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
- 244000080208 Canella winterana Species 0.000 description 7
- 235000008499 Canella winterana Nutrition 0.000 description 7
- 230000000767 anti-ulcer Effects 0.000 description 7
- 229940017545 cinnamon bark Drugs 0.000 description 7
- 239000003826 tablet Substances 0.000 description 7
- 230000000694 effects Effects 0.000 description 6
- 239000003814 drug Substances 0.000 description 5
- 239000008187 granular material Substances 0.000 description 5
- 229940079593 drug Drugs 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- 229920002261 Corn starch Polymers 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- FHRSHSOEWXUORL-HDJSIYSDSA-N cetraxate Chemical compound C1C[C@@H](C[NH3+])CC[C@@H]1C(=O)OC1=CC=C(CCC([O-])=O)C=C1 FHRSHSOEWXUORL-HDJSIYSDSA-N 0.000 description 3
- 229950009533 cetraxate Drugs 0.000 description 3
- 239000008120 corn starch Substances 0.000 description 3
- 229940099112 cornstarch Drugs 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 238000000926 separation method Methods 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 244000215068 Acacia senegal Species 0.000 description 2
- 244000223760 Cinnamomum zeylanicum Species 0.000 description 2
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- 229920000084 Gum arabic Polymers 0.000 description 2
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- 239000000205 acacia gum Substances 0.000 description 2
- 235000010489 acacia gum Nutrition 0.000 description 2
- 231100000215 acute (single dose) toxicity testing Toxicity 0.000 description 2
- 238000011047 acute toxicity test Methods 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 description 2
- 235000017803 cinnamon Nutrition 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 235000011852 gelatine desserts Nutrition 0.000 description 2
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 2
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 239000012669 liquid formulation Substances 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- 238000007911 parenteral administration Methods 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 210000002784 stomach Anatomy 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- ZORQXIQZAOLNGE-UHFFFAOYSA-N 1,1-difluorocyclohexane Chemical compound FC1(F)CCCCC1 ZORQXIQZAOLNGE-UHFFFAOYSA-N 0.000 description 1
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
- 241000251468 Actinopterygii Species 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- 206010042220 Stress ulcer Diseases 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- YKTSYUJCYHOUJP-UHFFFAOYSA-N [O--].[Al+3].[Al+3].[O-][Si]([O-])([O-])[O-] Chemical compound [O--].[Al+3].[Al+3].[O-][Si]([O-])([O-])[O-] YKTSYUJCYHOUJP-UHFFFAOYSA-N 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- 231100000403 acute toxicity Toxicity 0.000 description 1
- 230000007059 acute toxicity Effects 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000000843 anti-fungal effect Effects 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 239000006286 aqueous extract Substances 0.000 description 1
- 239000003125 aqueous solvent Substances 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- KJPRLNWUNMBNBZ-UHFFFAOYSA-N cinnamic aldehyde Natural products O=CC=CC1=CC=CC=C1 KJPRLNWUNMBNBZ-UHFFFAOYSA-N 0.000 description 1
- 229940117916 cinnamic aldehyde Drugs 0.000 description 1
- 239000003240 coconut oil Substances 0.000 description 1
- 235000019864 coconut oil Nutrition 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 235000008504 concentrate Nutrition 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 210000002249 digestive system Anatomy 0.000 description 1
- IJKVHSBPTUYDLN-UHFFFAOYSA-N dihydroxy(oxo)silane Chemical compound O[Si](O)=O IJKVHSBPTUYDLN-UHFFFAOYSA-N 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 208000000718 duodenal ulcer Diseases 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 238000005194 fractionation Methods 0.000 description 1
- 241000411851 herbal medicine Species 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 229960001375 lactose Drugs 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 1
- 235000012239 silicon dioxide Nutrition 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000001593 sorbitan monooleate Substances 0.000 description 1
- 235000011069 sorbitan monooleate Nutrition 0.000 description 1
- 229940035049 sorbitan monooleate Drugs 0.000 description 1
- 235000013599 spices Nutrition 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000008174 sterile solution Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Landscapes
- Medicines Containing Plant Substances (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
Description
【産業上の利用分野】本発明は３−フェニルプロペナー
ル誘導体を有効成分とする新規な抗潰瘍剤に関する。BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a novel anti-ulcer agent containing a 3-phenylpropenal derivative as an active ingredient.
【従来の技術および発明が解決しようとする課題】従来
より数多くの抗潰瘍剤が開発されてきたが、新規かつ有
用な抗潰瘍剤は常に求められている。ケイヒは漢方薬、
生薬製剤のみならず香辛料として世界中で用いられてい
る生薬である。また、代表的な芳香性健胃薬であるにも
かかわらず、その消化器系に対する薬理学的な研究報告
は少ない。ケイヒの水抽出エキスおよびケイヒに含まれ
るシンナムアルデヒドにストレス潰瘍モデルに対し有効
であることが報告されている［Ｐｌａｎｔａ ｍｅｄｉ
ｃａ，５２，４４０（１９８６），Ｃｈｅｍ．Ｐｈａｒ
ｍ．Ｂｕｌｌ．２３，９４１（１９７５）］が、他の抗
潰瘍作用成分に関する報告はない。ケイヒに含まれてい
る３−（２−メトキシフェニール）プロペナール［慣用
名 ｏ−メトキシシンナムアルデヒド（ ｏ−ｍｅｔｈ
ｏｘｙｃｉｎｎａｍａｌｄｅｈｙｄｅ）、以下この慣用
名でいう］に抗カビ作用をもつとの報告がなされている
［真菌誌，１９，１７２（１９７８）］。しかし、この
ものに抗潰瘍作用をもつことは従来知られていなかった
。BACKGROUND OF THE INVENTION Although many anti-ulcer agents have been developed, new and useful anti-ulcer agents are always in demand. Keihi is a Chinese herbal medicine.
It is a crude drug that is used all over the world not only in crude drug preparations but also as a spice. In addition, although it is a typical aromatic stomachic, there are few pharmacological research reports on its digestive system. It has been reported that the aqueous extract of cinnamon bark and cinnamaldehyde contained in cinnamon bark are effective against stress ulcer models [Planta medi
ca, 52, 440 (1986), Chem. Phar
m. Bull. 23,941 (1975)], but there are no reports regarding other anti-ulcer active ingredients. 3-(2-methoxyphenyl)propenal [common name o-methoxycinnamaldehyde (o-meth)] contained in cinnamon
It has been reported that oxycinnamaldehyde (hereinafter referred to by this common name) has an antifungal effect [Mycology Journal, 19, 172 (1978)]. However, it was not previously known that this substance had anti-ulcer effects.
【課題を解決するための手段】本発明者らは天然物の中
に、医薬品として開発可能な素材を見い出すことを目的
として、実験動物を用いた種々の病態モデルにおいてス
クリーニング試験を行ってきた。この過程において、抗
潰瘍実験モデルに対しケイヒに含まれる ｏ−メトキシ
シンナムアルデヒドに著明な抗潰瘍作用のあることを見
い出し、本発明を完成した。すなわち本発明は ｏ−メ
トキシシンナムアルデヒドを有効成分として含有する抗
潰瘍剤に関する。ｏ−メトキシシンナムアルデヒドは化
学式[Means for Solving the Problems] The present inventors have conducted screening tests in various pathological models using experimental animals with the aim of finding materials among natural products that can be developed as pharmaceuticals. During this process, we discovered that o-methoxycinnamaldehyde contained in cinnamon bark has a significant anti-ulcer effect on an anti-ulcer experimental model, and completed the present invention. That is, the present invention relates to an antiulcer agent containing o-methoxycinnamaldehyde as an active ingredient. o-Methoxycinnamaldehyde has the chemical formula
【化１】
を有する化合物である。ケイヒからの ｏ−メトキシシ
ンナムアルデヒドの単離は、まず低級アルキルケトン、
低級アルコール、低級脂肪酸エステル、低級脂肪族エー
テル等の有機溶剤で抽出し、ついでこの抽出液の濃縮物
をシリカゲル、アルミナ等を吸着剤とするカラムクロマ
トグラフィーに付すことにより行うことができる。低級
アルキルケトンとしては例えばアセトン、メチルエチル
ケトン等が、低級アルコールとしては例えばメタノール
、エタノール等が、低級脂肪酸エステルとしては、例え
ば酢酸エチル等が、低級脂肪族エーテルとしては例えば
エチルエーテル、イソプロピルエーテル等が用いられる
。
なお、有機溶剤による抽出操作にかえて、水蒸気蒸留に
よっても達成できる。ケイヒからの抽出分離例を参考例
に示す。本発明の抗潰瘍剤は ｏ−メトキシシンナムア
ルデヒドを有効成分として含有する。抗潰瘍剤の剤形は
限定的でなく、錠剤、カプセル剤、粉末剤、顆粒剤また
は経口的もしくは非経口的投与用の無菌溶液もしくは懸
濁液のような液状製剤の形であることができる。錠剤、
顆粒剤、粉末剤は必要に応じて本発明の有効成分を経口
投与するのに適しており、顆粒剤、粉末剤は必要に応じ
てカプセル剤として投与形態とすることができる。経口
投与用固形剤は慣用の製剤添加剤、例えば賦形剤（無水
ケイ酸、合成ケイ酸アルミニウム、乳糖、コーンスター
チ、微結晶セルロース等）、結合剤（アラビアゴム、ゼ
ラチン、ポリビニルピロリドン、ヒドロキシプロピルセ
ルロース等）、滑沢剤（ステアリン酸マグネシウム、タ
ルク、無水ケイ酸等）、崩壊剤（コーンスターチ、カル
ボキシメチルセルロースカルシウム等）等を含有するこ
とができる。錠剤は常法に従ってコーティングしてもよ
い。
経口用液状製剤は水性もしくは油性の懸濁液、溶液、シ
ロップ等の形態にすればよいが、また使用に先だって適
当な溶剤で再溶解し得る乾燥物であってもよい。このよ
うな液状製剤は普通に用いられる製剤添加剤、例えば水
、乳化剤（レシチン、ソルビタンモノオレート等）、分
散安定剤（カルボキシメチルセルロースナトリウム、ゼ
ラチン等）、非水性溶剤（ココナッツ油、落花生油等）
、酸化防止剤、着色剤、香味料等を含有することができ
る。非経口投与に用いるために ｏ−メトキシシンナム
アルデヒドを無菌溶剤中に溶解もしくは懸濁させて液状
製剤を得てもよい。溶液には常用の緩衝剤、等張化剤、
溶解補助剤などを含有させ得る。本発明の ｏ−メトキ
シシンナムアルデヒドを有効成分とする抗潰瘍剤はヒト
および動物の潰瘍、特に消化性潰瘍の治療および予防に
有効である。該化合物の有効量または投与量は潰瘍の程
度、患者の体質等の因子に応じて変動するが、一般にい
えば投与量は成人一人当たり１０〜５００ｍｇの範囲が
適当である。It is a compound having the following formula. To isolate o-methoxycinnamaldehyde from cinnamon, first a lower alkyl ketone,
This can be carried out by extracting with an organic solvent such as a lower alcohol, a lower fatty acid ester, or a lower aliphatic ether, and then subjecting the concentrated extract to column chromatography using silica gel, alumina, or the like as an adsorbent. Examples of lower alkyl ketones include acetone and methyl ethyl ketone; examples of lower alcohols include methanol and ethanol; examples of lower fatty acid esters include ethyl acetate; and examples of lower aliphatic ethers include ethyl ether and isopropyl ether. It will be done. Note that instead of the extraction operation using an organic solvent, it can also be achieved by steam distillation. An example of extraction and separation from cinnamon bark is shown as a reference example. The antiulcer agent of the present invention contains o-methoxycinnamaldehyde as an active ingredient. The dosage form of the anti-ulcer agent is not limited and can be in the form of a tablet, capsule, powder, granule or liquid preparation such as a sterile solution or suspension for oral or parenteral administration. . tablet,
Granules and powders are suitable for oral administration of the active ingredient of the present invention, and granules and powders can be made into capsules, if necessary. Solid preparations for oral administration contain conventional pharmaceutical additives, such as excipients (anhydrous silicic acid, synthetic aluminum silicate, lactose, cornstarch, microcrystalline cellulose, etc.), binders (gum arabic, gelatin, polyvinylpyrrolidone, hydroxypropyl cellulose, etc.). etc.), lubricants (magnesium stearate, talc, silicic anhydride, etc.), disintegrants (corn starch, calcium carboxymethyl cellulose, etc.), and the like. Tablets may be coated according to conventional methods. Oral liquid preparations may be in the form of aqueous or oily suspensions, solutions, syrups, etc., but may also be in the form of dry products that can be redissolved in an appropriate solvent prior to use. Such liquid formulations contain commonly used formulation additives, such as water, emulsifiers (lecithin, sorbitan monooleate, etc.), dispersion stabilizers (sodium carboxymethyl cellulose, gelatin, etc.), non-aqueous solvents (coconut oil, peanut oil, etc.)
, antioxidants, colorants, flavorings, etc. For use in parenteral administration, o-methoxycinnamaldehyde may be dissolved or suspended in a sterile solvent to obtain a liquid formulation. The solution contains commonly used buffers, tonicity agents,
It may contain a solubilizing agent and the like. The anti-ulcer agent of the present invention containing o-methoxycinnamaldehyde as an active ingredient is effective in treating and preventing ulcers, particularly peptic ulcers, in humans and animals. The effective amount or dosage of the compound varies depending on factors such as the degree of ulcer and the constitution of the patient, but generally speaking, the appropriate dosage is in the range of 10 to 500 mg per adult.
【実施例】ケイヒからの ｏ−メトキシシンナムアルデ
ヒドの抽出分離を参考例に、 ｏ−メトキシシンナムア
ルデヒドの抗潰瘍作用、急性毒性試験及び製剤例を実施
例に示す。
参考例（ケイヒからの抽出分離例）
ケイヒ５ｋｇをアセトン２５ｌに浸漬し、時々振り混ぜ
ながら３日間放置した。抽出液を減圧濃縮してエキス２
３０ｇを得た。これを５ｋｇのシリカゲルカラムクロマ
トグラフィー［シリカゲル６０、メルク社製、展開溶媒
：ベンゼン／アセトン＝１１／１（容量比）］に付して
分画した。目的物を含有する分画を合わせて濃縮し、再
クロマトグラフィーを行うことにより ｏ−メトキシシ
ンナムアルデヒドを得た。物理恒数および機器分析の結
果より、得られた成分は ｏ−メトキシシンナムアルデ
ヒドであることを確認した。
実施例１（抗潰瘍活性（ＨＣｌ／エタノール潰瘍））２
４時間絶食したＷｉｓｔａｒ系雄性ラット（体重２５０
〜２８０ｇ）に６０％エタノールと１５０ｍＭ ＨＣ
ｌからなるＨＣｌ／エタノール溶液をラット一匹当たり
１．５ｍｌ経口投与し、１時間後エーテル致死せしめた
。胃を摘出して２％ホルマリン１０ｍｌを胃内に入れて
１５分間固定した後、大弯にそって切り開き損傷の長さ
（ｍｍ）を測定した。一匹当たりの損傷の長さの合計を
潰瘍係数とした。
検体は５％アラビアゴム末で懸濁液とし、それぞれをＨ
Ｃｌ／エタノール投与の１時間前に経口投与した。コン
トロール群と検体投与群との潰瘍係数の差をコントロー
ル群の潰瘍係数で除して抑制率を算出した。結果を表１
に示す。[Example] Taking the extraction and separation of o-methoxycinnamaldehyde from cinnamon bark as a reference example, the anti-ulcer effect, acute toxicity test and formulation examples of o-methoxycinnamaldehyde are shown in the example. Reference Example (extraction and separation example from cinnamon bark) 5 kg of cinnamon bark was immersed in 25 liters of acetone and left for 3 days with occasional shaking. Concentrate the extract under reduced pressure to obtain Extract 2
30g was obtained. This was subjected to 5 kg of silica gel column chromatography [silica gel 60, manufactured by Merck & Co., Ltd., developing solvent: benzene/acetone = 11/1 (volume ratio)] for fractionation. Fractions containing the target product were combined, concentrated, and rechromatographed to obtain o-methoxycinnamaldehyde. From the results of physical constants and instrumental analysis, it was confirmed that the obtained component was o-methoxycinnamaldehyde. Example 1 (Anti-ulcer activity (HCl/ethanol ulcer)) 2
Wistar male rats (body weight 250
~280g) with 60% ethanol and 150mM HC
Each rat was orally administered 1.5 ml of an HCl/ethanol solution consisting of 1.5 ml of HCl/ethanol solution, and was sacrificed with ether after 1 hour. The stomach was removed, 10 ml of 2% formalin was put into the stomach and fixed for 15 minutes, and then an incision was made along the greater curvature to measure the length (mm) of the injury. The total length of lesions per animal was defined as the ulcer index. The samples were suspended in 5% gum arabic powder, and each
It was administered orally 1 hour before Cl/ethanol administration. The inhibition rate was calculated by dividing the difference in ulcer coefficient between the control group and the sample administration group by the ulcer coefficient of the control group. Table 1 shows the results.
Shown below.
【表１】
─────────────────────────
────────── 検体
用量 動物数 潰瘍係数１）
抑制率 備考
（ｍｇ／ｋｇ） （匹）
（％）──────
─────────────────────────
──── コントロール −
６ １３２．７±１２．２
− ｏ−メトキシシンナムアルテ゛ヒト゛
２５ ５ ６．８±１．７
＊ ９４．９ 本発明
５０
６ ０．０±０．０＊ １００．０
本発明 塩酸セトラキサート２）
３００ ５ ５．５±
２．２＊ ９５．９ 比較例─────
─────────────────────────
───── ＊ｐ＜０．０１
１）数値は１群の平均値±標準誤差を示す。
２）塩酸セトラキサート（ｃｅｔｒａｘａｔｅ ｈｙｄ
ｒｏｃｈｌｏｒｉｄｅ）[Table 1] ──────────────────────────
────────── Specimen
Dose Number of animals Ulcer index 1)
Suppression rate Notes
(mg/kg) (fish)
(%)──────
──────────────────────────
──── Control −
6 132.7±12.2
- o-Methoxycinnamalterine human
25 5 6.8±1.7
*94.9 This invention
50
6 0.0±0.0* 100.0
Present invention Cetraxate hydrochloride 2)
300 5 5.5±
2.2* 95.9 Comparative example─────
──────────────────────────
────── *p<0.01 1) Values indicate the mean value ± standard error of one group. 2) Cetraxate hydrochloride (cetraxate hydr)
rochloride)
【化２】
は代表的抗潰瘍剤である。
実施例２（急性毒性）
ｄｄ−Ｙ系雄マウス（体重２３〜２７ｇ）１群１０匹を
用いて単回経口投与による急性毒性試験を行った。本発
明の有効成分である ｏ−メトキシシンナムアルデヒド
のＬＤ５０値は２０００ｍｇ／ｋｇより大であり、有効
量にくらべて高い安全性が確認された。
実施例３（経口投与に適した薬剤（錠剤））以下の成分
を混和し、得られた混合物を打錠器で形成することによ
り錠剤を製造する。
錠剤当たりの量（ｍｇ） ｏ−メ
トキシシンナムアルデヒド ２５
コーンスターチ
２０ ヒドロキシプロピルセルロース
３ ステアリン酸マグネシウ
ム ２ 乳糖
適量─────────────────
────── 計
１５０実施例４
（経口投与に適した薬剤（顆粒剤））以下の成分をとり
、常法に従って顆粒剤を製造する。[Chemical formula 2] is a typical anti-ulcer agent. Example 2 (Acute Toxicity) An acute toxicity test was conducted by single oral administration using 1 group of 10 dd-Y male mice (body weight 23-27 g). The LD50 value of o-methoxycinnamaldehyde, which is the active ingredient of the present invention, was greater than 2000 mg/kg, confirming high safety compared to the effective dose. Example 3 (Medicine (tablet) suitable for oral administration) Tablets are manufactured by mixing the following ingredients and forming the resulting mixture in a tablet press.
Amount per tablet (mg) o-methoxycinnamaldehyde 25
corn starch
20 Hydroxypropylcellulose
3 Magnesium stearate 2 Lactose
Appropriate amount──────────────────
────── Total
150 Example 4
(Drug suitable for oral administration (granules)) Prepare granules using the following ingredients according to a conventional method.
【発明の効果】従来、抗潰瘍作用が知られていなかった
ｏ−メトキシシンナムアルデヒドを有効成分とする抗
潰瘍剤を提供する。[Effects of the Invention] The present invention provides an anti-ulcer agent containing o-methoxycinnamaldehyde as an active ingredient, whose anti-ulcer effect has not been known so far.
Claims (1)
ペナールを有効成分として含有する抗潰瘍剤。1. An antiulcer agent containing 3-(2-methoxyphenyl)propenal as an active ingredient.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP03136460A JP3102908B2 (en) | 1991-06-07 | 1991-06-07 | Anti-ulcer agent containing 3-phenylpropenal derivative as active ingredient |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP03136460A JP3102908B2 (en) | 1991-06-07 | 1991-06-07 | Anti-ulcer agent containing 3-phenylpropenal derivative as active ingredient |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH04360829A true JPH04360829A (en) | 1992-12-14 |
| JP3102908B2 JP3102908B2 (en) | 2000-10-23 |
Family
ID=15175635
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP03136460A Expired - Fee Related JP3102908B2 (en) | 1991-06-07 | 1991-06-07 | Anti-ulcer agent containing 3-phenylpropenal derivative as active ingredient |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP3102908B2 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US11427538B2 (en) * | 2017-04-28 | 2022-08-30 | Kyoto University | Organic tellurium compound, method for producing same, living radical polymerization initiator, method for producing vinyl polymer, and vinyl polymer |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP4349435B2 (en) | 2007-05-28 | 2009-10-21 | パナソニック電工株式会社 | Oscillating motion device |
-
1991
- 1991-06-07 JP JP03136460A patent/JP3102908B2/en not_active Expired - Fee Related
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US11427538B2 (en) * | 2017-04-28 | 2022-08-30 | Kyoto University | Organic tellurium compound, method for producing same, living radical polymerization initiator, method for producing vinyl polymer, and vinyl polymer |
Also Published As
| Publication number | Publication date |
|---|---|
| JP3102908B2 (en) | 2000-10-23 |
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