JPS62174020A - Remedy for acute gastritis - Google Patents
Remedy for acute gastritisInfo
- Publication number
- JPS62174020A JPS62174020A JP61237091A JP23709186A JPS62174020A JP S62174020 A JPS62174020 A JP S62174020A JP 61237091 A JP61237091 A JP 61237091A JP 23709186 A JP23709186 A JP 23709186A JP S62174020 A JPS62174020 A JP S62174020A
- Authority
- JP
- Japan
- Prior art keywords
- methyl
- active ingredient
- acute gastritis
- parts
- pge2
- 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
Links
- 208000007882 Gastritis Diseases 0.000 title claims abstract description 18
- XSGQFHNPNWBVPT-VFXMVCAWSA-N 15-methyl-15R-PGE2 Chemical compound CCCCC[C@@](C)(O)\C=C\[C@H]1[C@H](O)CC(=O)[C@@H]1C\C=C/CCCC(O)=O XSGQFHNPNWBVPT-VFXMVCAWSA-N 0.000 claims abstract description 15
- 239000004480 active ingredient Substances 0.000 claims abstract description 8
- 239000003814 drug Substances 0.000 claims description 13
- 229940124597 therapeutic agent Drugs 0.000 claims description 7
- 239000000843 powder Substances 0.000 abstract description 7
- 150000001875 compounds Chemical class 0.000 abstract description 6
- 239000001913 cellulose Substances 0.000 abstract description 5
- 229920002678 cellulose Polymers 0.000 abstract description 5
- 239000002775 capsule Substances 0.000 abstract description 3
- 230000001120 cytoprotective effect Effects 0.000 abstract description 3
- 230000027119 gastric acid secretion Effects 0.000 abstract description 3
- 229920002472 Starch Polymers 0.000 abstract description 2
- 239000008107 starch Substances 0.000 abstract description 2
- 235000019698 starch Nutrition 0.000 abstract description 2
- 239000007858 starting material Substances 0.000 abstract description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 abstract 2
- 239000002671 adjuvant Substances 0.000 abstract 1
- 238000007796 conventional method Methods 0.000 abstract 1
- 230000002401 inhibitory effect Effects 0.000 abstract 1
- 235000014655 lactic acid Nutrition 0.000 abstract 1
- 239000004310 lactic acid Substances 0.000 abstract 1
- 230000002688 persistence Effects 0.000 abstract 1
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- 230000000694 effects Effects 0.000 description 11
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 8
- 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 8
- 230000006378 damage Effects 0.000 description 8
- 230000002496 gastric effect Effects 0.000 description 8
- 239000008101 lactose Substances 0.000 description 8
- 150000004667 medium chain fatty acids Chemical class 0.000 description 7
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 7
- 229920002261 Corn starch Polymers 0.000 description 6
- 230000001154 acute effect Effects 0.000 description 6
- 239000008120 corn starch Substances 0.000 description 6
- 239000008187 granular material Substances 0.000 description 6
- 238000002360 preparation method Methods 0.000 description 6
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 5
- 229960002986 dinoprostone Drugs 0.000 description 5
- 229940079593 drug Drugs 0.000 description 5
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 5
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 5
- 238000004519 manufacturing process Methods 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- 241000700159 Rattus Species 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 208000027418 Wounds and injury Diseases 0.000 description 4
- 235000010980 cellulose Nutrition 0.000 description 4
- 210000001156 gastric mucosa Anatomy 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
- 235000010355 mannitol Nutrition 0.000 description 4
- 201000010099 disease Diseases 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 230000003628 erosive effect Effects 0.000 description 3
- 208000014674 injury Diseases 0.000 description 3
- 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 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 230000009858 acid secretion Effects 0.000 description 2
- 229940069428 antacid Drugs 0.000 description 2
- 239000003159 antacid agent Substances 0.000 description 2
- 230000002467 anti-pepsin effect Effects 0.000 description 2
- 208000010643 digestive system disease Diseases 0.000 description 2
- 231100000673 dose–response relationship Toxicity 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 239000007902 hard capsule Substances 0.000 description 2
- 230000003902 lesion Effects 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- XEYBRNLFEZDVAW-UHFFFAOYSA-N prostaglandin E2 Natural products CCCCCC(O)C=CC1C(O)CC(=O)C1CC=CCCCC(O)=O XEYBRNLFEZDVAW-UHFFFAOYSA-N 0.000 description 2
- 230000001681 protective effect Effects 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 239000007901 soft capsule Substances 0.000 description 2
- 239000005995 Aluminium silicate Substances 0.000 description 1
- 239000004375 Dextrin Substances 0.000 description 1
- 229920001353 Dextrin Polymers 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 125000002575 PGE2 group Chemical group 0.000 description 1
- 208000008469 Peptic Ulcer Diseases 0.000 description 1
- 108091006629 SLC13A2 Proteins 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-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
- 235000012211 aluminium silicate Nutrition 0.000 description 1
- 229940035674 anesthetics Drugs 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000002429 anti-coagulating effect Effects 0.000 description 1
- 239000012752 auxiliary agent Substances 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 229940084030 carboxymethylcellulose calcium Drugs 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 208000023652 chronic gastritis Diseases 0.000 description 1
- 231100000749 chronicity Toxicity 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 235000019425 dextrin Nutrition 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 102000038379 digestive enzymes Human genes 0.000 description 1
- 108091007734 digestive enzymes Proteins 0.000 description 1
- 229960001342 dinoprost Drugs 0.000 description 1
- XEYBRNLFEZDVAW-ARSRFYASSA-N dinoprostone Chemical compound CCCCC[C@H](O)\C=C\[C@H]1[C@H](O)CC(=O)[C@@H]1C\C=C/CCCC(O)=O XEYBRNLFEZDVAW-ARSRFYASSA-N 0.000 description 1
- 238000007907 direct compression Methods 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 229940088598 enzyme Drugs 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 210000004211 gastric acid Anatomy 0.000 description 1
- 210000004051 gastric juice Anatomy 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 239000003193 general anesthetic agent Substances 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 238000006317 isomerization reaction Methods 0.000 description 1
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 210000005037 parasympathetic nerve Anatomy 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- -1 sucrose fatty acid ester Chemical class 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000002636 symptomatic treatment Methods 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 239000003204 tranquilizing agent Substances 0.000 description 1
- 230000002936 tranquilizing effect Effects 0.000 description 1
- 238000011282 treatment Methods 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/45—Non condensed piperidines, e.g. piperocaine having oxo groups directly attached to the heterocyclic ring, e.g. cycloheximide
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
【発明の詳細な説明】
の−１
本発明は、医薬、特に急性胃炎の治療剤に関するもので
ある。DETAILED DESCRIPTION OF THE INVENTION (1) The present invention relates to a medicament, particularly a therapeutic agent for acute gastritis.
１末立笠潴
本発明化合物の１５（Ｒ）−１５−メチル−プロスタグ
ランジンＥ２（以下ｒ１５ （Ｒ）−１５−メチル−Ｐ
ＧＥ２」という）が、胃酸分泌抑制作用、及び細胞保護
（サイトプロテクション）作用ををすることは既知であ
る。即ち、現在、消化性潰瘍治療剤として研究が行われ
いる〔特開昭５１−１１２５０８号公報、ダイジェステ
ィブ・ディジーズイズ・エンド・サイエンスイズ（Ｄｉ
ｇｅｓｔｉｖｅ Ｄｉｓｅａｓｅｓ ａｎｄ ５ｃｉ
ｅｎｃｅｓ） ２Ａ（５）＋３８１ （１９７９）、
ガツト（Ｇｕｔ） ２１２Ｊ７２８ （１９８１）〕
。15(R)-15-methyl-prostaglandin E2 (r15(R)-15-methyl-P) of the compound of the present invention
It is known that GE2) has a gastric acid secretion suppressing effect and a cytoprotective effect. That is, research is currently being conducted as a therapeutic agent for peptic ulcers [Japanese Unexamined Patent Publication No. 51-112508, Digestive Diseases End Sciences (Digestive Diseases End Sciences)].
gestive Diseases and 5ci
ences) 2A(5)+381 (1979),
Gut 212J728 (1981)]
.
胃炎は、通常、病因論的あるいは臨床的に急性胃炎と慢
性胃炎に分けて論じられており、各々独立した別個の疾
患単位と考えるのが妥当であるとされている。一般に急
性胃炎とは、内因性及び外因性の刺激により急激に発症
する胃粘膜の炎症性病変のことを言い、比較的短期間の
経過て治ゆするものであり、原則として慢性化への移行
はないとされている。Gastritis is usually discussed etiologically or clinically as acute gastritis and chronic gastritis, and it is considered appropriate to consider each as an independent and distinct disease unit. In general, acute gastritis refers to an inflammatory lesion of the gastric mucosa that develops rapidly due to endogenous or exogenous stimuli.It heals after a relatively short period of time, and as a general rule, the disease progresses to chronicity. It is said that there is no such thing.
本発明は上記の意味での急性胃炎の治療剤の提供を目的
としている。The present invention aims to provide a therapeutic agent for acute gastritis in the above sense.
ｌｌ ≦ よ” 。ll ≦ .
従来、急性胃炎に対しては、その対症療法の一つとして
制酸剤、副交感神経遮断剤、抗ペプシン剤、粘膜麻酔剤
、粘膜保護剤、総合消化酵素剤、精神安定剤等が用いら
れてきた。しかしながら、例えば、制酸剤の場合は酸に
よる痛みの消失には著効を示すが、酸分泌を抑制する作
用はなく、又、抗ペプシン剤の場合は副作用として抗血
液凝固作用を有する等、各々欠点を何する。Conventionally, antacids, parasympathetic nerve blockers, antipepsin agents, mucosal anesthetics, mucosal protectants, general digestive enzymes, tranquilizers, etc. have been used as symptomatic treatments for acute gastritis. Ta. However, for example, antacids are highly effective in eliminating pain caused by acid, but do not have the effect of suppressing acid secretion, and anti-pepsin drugs have anti-coagulant effects as a side effect. What are the drawbacks of each?
以上のように急性胃炎に対しては多数の薬剤が使用され
てきているが、現時点でその効果が確認されているもの
は少ない。そこで、急性胃炎に対して何効且つ副作用の
少ない薬剤の登場が期待されていた。As mentioned above, a large number of drugs have been used to treat acute gastritis, but at present only a few have been confirmed to be effective. Therefore, the emergence of a drug that is effective against acute gastritis and has fewer side effects has been expected.
本発明の目的は、従来品に見られた欠陥ををさない優れ
た急性胃炎治療剤を提供することにある。An object of the present invention is to provide an excellent therapeutic agent for acute gastritis that does not have the defects found in conventional products.
、ｊ ｆ −ための：・
本発明者は、」１記の目的を達成すべく種々研究、検討
した結果、実験動物において、該１５（Ｒ）−１５−メ
チル−ＰＧＥ２を前処理することにより、各種急性胃粘
膜惹起物質による急性胃炎の発生を強く抑制する効果を
見い出し、本発明を完成させるに至った。, j f -: As a result of various studies and examinations to achieve the purpose stated in 1., the present inventors have determined that by pre-treating the 15(R)-15-methyl-PGE2 in experimental animals, They have discovered the effect of strongly suppressing the occurrence of acute gastritis caused by various acute gastric mucosa-inducing substances, and have completed the present invention.
即ち、本発明は、１５（Ｒ）−１５−メチル−ＰＧＥ２
を有効成分として含有することを特徴とする急性胃炎治
療剤である。That is, the present invention provides 15(R)-15-methyl-PGE2
This is a therapeutic agent for acute gastritis characterized by containing as an active ingredient.
本発明においてを効成分として用いることのできる１５
（Ｒ）−１５−メチル−ＰＧＥ２は、特公昭５２−２５
号公報に記載の既知物質であり、１５（Ｒ）−１５−メ
チル−プロスタグランジンＦ２（以下ｒ１５ （Ｒ）
−１５−メチル−ＰＧＦ２」という）を出発物質とする
反応によって製造出来る。15 that can be used as an active ingredient in the present invention
(R)-15-methyl-PGE2 is
15(R)-15-methyl-prostaglandin F2 (r15 (R)
-15-methyl-PGF2) as a starting material.
次に、本物質を急性胃炎治療剤として適用するための製
剤化について説明する。Next, formulation of this substance for use as a therapeutic agent for acute gastritis will be explained.
本物質は胃酸によって異性化を起こし、活性体となって
薬効を発揮することから、製剤としては、経口可能なも
のが望ましい。Since this substance undergoes isomerization in the presence of stomach acid and becomes an active form, which exhibits medicinal efficacy, it is desirable that the preparation be one that can be taken orally.
本物質は、常法により補助剤とともに医薬として用いら
れる担体と混合して、カプセル、散剤、細粒剤、顆粒剤
、錠剤、液剤、懸濁剤、乳剤、ドライシロップとするこ
とができる。これらの場合の医薬用担体としては、例え
ば、乳糖、デンプン、結晶セルロース、ステアリン酸マ
グネシウム、Ｄ−マンニトール、ヒドロキシプロピルセ
ルロース、デキストリン、白糖、カオリン、炭酸カルシ
ウム、タルク、ショ糖脂肪酸エステル、カルボキシメチ
ルセルロースカルシウム、カルボキシメチルセルロース
ナトリウム、中鎖脂肪酸トリグリセライド等が好ましい
。This substance can be mixed with a pharmaceutically acceptable carrier together with auxiliary agents in a conventional manner to form capsules, powders, fine granules, granules, tablets, solutions, suspensions, emulsions, and dry syrups. Pharmaceutical carriers in these cases include, for example, lactose, starch, crystalline cellulose, magnesium stearate, D-mannitol, hydroxypropyl cellulose, dextrin, white sugar, kaolin, calcium carbonate, talc, sucrose fatty acid ester, carboxymethyl cellulose calcium. , sodium carboxymethyl cellulose, medium chain fatty acid triglyceride, and the like are preferred.
本則の投与量は、対象が動物かヒトにより、又、年令、
個人差、病状等に影響されるが、酸分泌を抑制する量よ
り少ない量、即ち、細胞保護作用を発揮する量であれば
よく、一般に１日量として、−ご−
成人１人当たり、０．１〜１００μｇ１好ましくは１〜
５０μｇ１さらに好ましくは２〜３０μｇを３〜４回に
分けて経口剤として投与する。The basic dosage depends on whether the subject is an animal or a human, and on age and age.
Although it is influenced by individual differences, medical conditions, etc., it is sufficient that the amount is smaller than the amount that suppresses acid secretion, that is, the amount that exerts a cell protective effect.Generally, the daily dose is 0.00000 for each adult. 1 to 100 μg 1 preferably 1 to 100 μg
50 μg, more preferably 2 to 30 μg, is administered in 3 to 4 divided doses as an oral preparation.
創ｊ
本発明化合物は、胃酸分泌抑制作用、細胞保護作用等を
仔し、急性胃炎の治療に適している。Wound j The compound of the present invention has a gastric acid secretion suppressing effect, a cell protective effect, etc., and is suitable for the treatment of acute gastritis.
本発明化合物は細胞保護作用及び強い胃液分泌抑制作用
を有するＰＧＥ２の持つ欠点、即ち、生物学的半減期が
極めて短かいということを克服したものである。つまり
、ＰＧＥ２の１５位にメチル基を導入することによって
、ＰＧ代謝酵素から保護し、作用の持続化をはかったも
のである。The compound of the present invention overcomes the disadvantage of PGE2, which has a cytoprotective effect and a strong gastric juice secretion suppressing effect, that is, it has an extremely short biological half-life. That is, by introducing a methyl group into the 15th position of PGE2, it is protected from PG metabolic enzymes and its action is prolonged.
又、本発明化合物である１５（Ｒ）−１５−メチル−Ｐ
ＧＥ２（２体）は、胃酸により、そのエピマ一体である
８体に変化し、その作用が増強されることが知られてい
る。In addition, the compound of the present invention, 15(R)-15-methyl-P
It is known that GE2 (2 forms) changes into 8 forms, which are its epimers, by gastric acid, and its action is enhanced.
以下に、実験例、および実施例を示すが、本発明はこれ
に限定されるものではない。Experimental examples and examples are shown below, but the present invention is not limited thereto.
実験例１
［無水エタノール誘発胃粘膜障害試験コ２４時間絶食、
１８時間絶木の雄ＳＤ系ラットに無水エタノール （１
ｍｌ／ｈｅａｄ） を経口投与し、１時間後に胃粘膜
上の損傷の長さを測定し、その総和をもってびらん指数
（ｍｍ） とした。１５（Ｒ）−１５−メチル−ＰＧ
Ｅ２はエタノール投与３０分前に経口投与した。その結
果、表１に示したように、１５（Ｒ）−１５−メチル−
ＰＧＥ２はエタノール投与による胃病変の発生を用量依
存的に抑制し、ＥＤ５ｏ値は０．３〜１μｇ／ｋｇ と
推定された。Experimental Example 1 [Anhydrous ethanol-induced gastric mucosal damage test: 24-hour fasting,
Absolute ethanol (1
ml/head) was orally administered, and 1 hour later, the length of damage on the gastric mucosa was measured, and the sum total was defined as the erosion index (mm). 15(R)-15-methyl-PG
E2 was orally administered 30 minutes before ethanol administration. As a result, as shown in Table 1, 15(R)-15-methyl-
PGE2 suppressed the occurrence of gastric lesions due to ethanol administration in a dose-dependent manner, and the ED5o value was estimated to be 0.3-1 μg/kg.
尚、試験は盲検法で実施した。The test was conducted in a blinded manner.
表１
ラットにおける無水エタノール誘発急性胃粘膜の効果
＊＊ ：ｐ＜Ｏ，Ｏｆ、 ＊本末 ：Ｐ＜０．
００１尚、前記の抑制率は次式を用いて算出した。Table 1 Absolute ethanol-induced acute gastric mucosal effects in rats**: p<O, Of, *End of book: P<0.
001 The above-mentioned inhibition rate was calculated using the following formula.
Ｘ １００
コントロール群のびらん指数 （％）実験
例２
［０，６Ｎ ＨＣＩ、 ０．２Ｎ ＮａＯＨ，２５％
ＮａＣ１誘発胃粘膜障害試験］
４８時間絶食、２４時間絶木の雄Ｓ、Ｄ系ラットに、０
．６Ｎ ＨＣＩ、 ０．２Ｎ ＮａＯＨおよび２５％Ｎ
ａＣ］ 溶液を各々１ｍｌ／ｈｅａｄの割合で経口投与
した。投与１時間後に胃粘膜上の損傷の長さを測定し、
その総和を持ってびらん指数（ｍｍ）とした。X 100 Erosion index of control group (%) Experimental example 2 [0.6N HCI, 0.2N NaOH, 25%
NaC1-induced gastric mucosal damage test] 0
．． 6N HCI, 0.2N NaOH and 25%N
aC] Each solution was orally administered at a rate of 1 ml/head. One hour after administration, the length of damage on the gastric mucosa was measured,
The total sum was taken as the erosion index (mm).
１５（Ｒ）−１５−メチル−ＰＧＥ２は惹起物質投与３
０分前に経口投与した。尚、試験はいずれも盲検法で実
施した。15(R)-15-methyl-PGE2 is induced substance administration 3
Administered orally 0 minutes before administration. All tests were conducted in a blinded manner.
その結果、表２．３．４に示したように、１５（Ｒ）−
１５−メチル−ＰＧＥ２はこれら薬物による急性胃粘膜
障害の発生を用量依存的に抑制し、ＥＤ５ｏ値は０．６
ＮＨＣ１で３〜１０ μｇ／ｋｇ 。As a result, as shown in Table 2.3.4, 15(R)-
15-Methyl-PGE2 suppresses the occurrence of acute gastric mucosal damage caused by these drugs in a dose-dependent manner, with an ED5o value of 0.6.
3-10 μg/kg for NHC1.
０、２Ｎ ＮａＯＨおよび２５％ＮａＣｌ では１〜３
μｇ／ｋ ｇ と推定された。1-3 for 0,2N NaOH and 25% NaCl
It was estimated to be μg/kg.
表２
ラットにおける０、 １３Ｎ ＨＣＩ 誘発急性胃粘膜
障害に対する１５（Ｒ）＝１５−メチル−ＰＧＥ２の効
果
＊＊、：ｐ＜Ｑ、ｏｉ、 零＊＊ ：Ｐ＜０．００１
表３
ラットにおける０、 ２Ｎ ＮａＯＨ誘発急性胃粘膜障
害に対する１５（Ｒ）−１５−メチル−ＰＧＥ２の効果
木本＊ ：ｐ＜ｏ、 ｏｏｉ
＝１０−
表４
ラットにおける２５％ＮａＣｌ 誘発急性胃粘膜障害に
対する１５（Ｒ）−１５−メチル−ＰＧＥ２の効果
実施例１
［軟カプセル剤の製造］
１５（Ｒ）−１５−メチル−ＰＧＥ２０．００５部中鎖
脂肪酸トリグリセライド ９９．９９５部（部は
特記しない限り重量を示す）
１５（Ｒ）−１５−メチル−ＰＧＥ２を中鎖脂肪酸トリ
グリセライドに溶解し、これをロータリー法によって軟
カプセルに製した。Table 2 Effect of 15(R)=15-methyl-PGE2 on 0, 13N HCI-induced acute gastric mucosal injury in rats**: p<Q, oi, zero**: P<0.001
Table 3 Effect of 15(R)-15-methyl-PGE2 on 0, 2N NaOH-induced acute gastric mucosal injury in rats Kimoto*: p<o, ooi = 10- Table 4 25% NaCl-induced acute gastric mucosal injury in rats Effect of 15(R)-15-methyl-PGE2 on Example 1 [Manufacture of soft capsules] 20.005 parts of 15(R)-15-methyl-PGE Medium chain fatty acid triglyceride 99.995 parts (unless otherwise specified) Weight is shown) 15(R)-15-methyl-PGE2 was dissolved in medium chain fatty acid triglyceride, and this was made into soft capsules by a rotary method.
実施例２
［硬カプセル剤の製造コ
１５（Ｒ）−１５−メチル−ＰＧＥ２０．００５部中鎖
脂肪酸トリグリセライド ９９．９９５部１５（
Ｒ）−１５−メチル−ＰＧＥ２を中鎖脂肪酸トリグリセ
ライドに溶解し、これを日周４号カプセルに充填し、接
合部をシールして硬カプセルに製した。Example 2 [Production of hard capsules] 15(R)-15-methyl-PGE 20.005 parts Medium chain fatty acid triglyceride 99.995 parts 15 (
R)-15-methyl-PGE2 was dissolved in medium-chain fatty acid triglyceride, and this was filled into a No. 4 diurnal capsule, and the joint was sealed to make a hard capsule.
実施例３
［散剤の製造コ
１５（Ｒ）−１５−メチル−ＰＧＥ２０．０１部トウモ
ロコシデンプン １００．００部乳糖
８９９．９９部１５（Ｒ）−１５−メチル
−ＰＧＥ２、乳糖、トウモロコシデンプンを各々篩遇し
た後、混合し散剤とした。Example 3 [Production of powder] 15(R)-15-methyl-PGE 20.01 parts Corn starch 100.00 parts Lactose
899.99 parts of 15(R)-15-methyl-PGE2, lactose, and corn starch were each sieved and mixed to form a powder.
実施例４
［細粒剤の製造コ
１５（Ｒ）−１５−メチル−ＰＧＥ２０．低部乳糖
４２０．００部結晶セルロース
ｉｏｏ、 ｏｏ部Ｄ−マンニトール
４４７．９９部ヒドロキシプロピルセルロース
３２．００部先ず、１５（Ｒ）−１５−メチル−ＰＧ
Ｅ２ とＤ−マンニトールを用いて主薬の１００倍散を
作った後、これに乳糖、結晶セルロース、残りのＤ−マ
ンニトールを加えて混合し、５％ヒドロキシプロピルセ
ルロース溶液をバインダーとして造粒し、細粒剤とした
。Example 4 [Production of fine granules] 15(R)-15-methyl-PGE20. low lactose
420.00 parts crystalline cellulose
ioo, oo part D-mannitol
447.99 parts hydroxypropyl cellulose
32.00 parts First, 15(R)-15-methyl-PG
After making a 100% powder of the main drug using E2 and D-mannitol, lactose, crystalline cellulose, and the remaining D-mannitol were added and mixed, and the powder was granulated using a 5% hydroxypropyl cellulose solution as a binder. It was made into granules.
実施例５
［顆粒剤の製造コ
１５（Ｒ）−１５−メチル−ＰＧＥ２０．０１部乳糖
８３９．９９部トウモロコシデンプン
１５０．００部ヒドロキシプロピルセルロ
ース １０．０ｎ１５（Ｒ）−１５−メチル−Ｐ Ｇ
Ｅ、、とヒドロキシプロピルセルロースを、５０％エ
タノール溶液と成し、混合した乳糖、トウモロコシデン
プンに加えて造粒・乾燥し、篩過にて１２ｍｅ ｓ ｈ
通過、６０ｍｅｓｈ不通過のものを顆粒剤とした。Example 5 [Production of granules] 15(R)-15-methyl-PGE 20.01 parts lactose
839.99 parts Corn starch 150.00 parts Hydroxypropyl cellulose 10.0n15(R)-15-methyl-PG
E, and hydroxypropyl cellulose were made into a 50% ethanol solution, added to the mixed lactose and corn starch, granulated and dried, and filtered through a sieve for 12 me h.
Those that passed through but did not pass through 60 mesh were made into granules.
１２一
実施例６
［錠剤の製造コ
１５（Ｒ）−１５−メチル−ＰＧＥ２０．００５部乳糖
９４．０００部トウモロコシデン
プン ３４．０００部結晶セルロース
２０．９９５部ステアリン酸マグネシウム
１．０００部先ず、１５（Ｒ）−１５−メチ
ル−ＰＧＥ２とトウモロコシデンプンの混合によって、
１０％主薬倍散末を作り、これに他の原料を混合し、直
接打錠により、直径７．０ｍｍ錠剤とした。121 Example 6 [Preparation of tablets] 15(R)-15-methyl-PGE 20.005 parts Lactose 94.000 parts Corn starch 34.000 parts Crystalline cellulose
20.995 parts Magnesium stearate 1.000 parts First, by mixing 15(R)-15-methyl-PGE2 and corn starch,
A 10% active ingredient powder was prepared, other raw materials were mixed with this, and tablets with a diameter of 7.0 mm were made by direct compression.
実施例７
［液剤の製造コ
１５（Ｒ）−１５−メチル−ＰＧＥ２０．００１部中鎖
脂肪酸トリグリセライド ９９．９９９部１５（Ｒ
）−１５−メチル−ＰＧＥ２を中鎖脂肪酸トリグリセラ
イドに溶解することにより、液剤とした。Example 7 [Preparation of liquid preparation 20.001 parts of 15(R)-15-methyl-PGE 99.999 parts of medium chain fatty acid triglyceride 15(R)
)-15-methyl-PGE2 was dissolved in medium-chain fatty acid triglyceride to prepare a liquid preparation.
Claims (1)
を有効成分として含有することを特徴とする急性胃炎治
療剤。15(R)-15-methyl-prostaglandin E_2
A therapeutic agent for acute gastritis characterized by containing as an active ingredient.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP22348385 | 1985-10-09 | ||
| JP60-223483 | 1985-10-09 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPS62174020A true JPS62174020A (en) | 1987-07-30 |
Family
ID=16798838
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP61237091A Pending JPS62174020A (en) | 1985-10-09 | 1986-10-07 | Remedy for acute gastritis |
Country Status (2)
| Country | Link |
|---|---|
| JP (1) | JPS62174020A (en) |
| KR (1) | KR870003785A (en) |
-
1986
- 1986-10-07 JP JP61237091A patent/JPS62174020A/en active Pending
- 1986-10-08 KR KR1019860008453A patent/KR870003785A/en not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| KR870003785A (en) | 1987-05-04 |
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