JPS63250322A - Remedy for alimentary disease - Google Patents
Remedy for alimentary diseaseInfo
- Publication number
- JPS63250322A JPS63250322A JP8359287A JP8359287A JPS63250322A JP S63250322 A JPS63250322 A JP S63250322A JP 8359287 A JP8359287 A JP 8359287A JP 8359287 A JP8359287 A JP 8359287A JP S63250322 A JPS63250322 A JP S63250322A
- Authority
- JP
- Japan
- Prior art keywords
- remedy
- ester
- compound
- formula
- salt
- 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
- 201000010099 disease Diseases 0.000 title abstract 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title abstract 3
- 150000003839 salts Chemical class 0.000 claims abstract description 14
- 150000002148 esters Chemical class 0.000 claims abstract description 9
- -1 5-substituted tetrazol Chemical class 0.000 claims abstract description 8
- 239000004480 active ingredient Substances 0.000 claims abstract description 7
- 208000010643 digestive system disease Diseases 0.000 claims description 4
- 239000003814 drug Substances 0.000 claims description 4
- 231100000252 nontoxic Toxicity 0.000 claims description 4
- 230000003000 nontoxic effect Effects 0.000 claims description 4
- 229940124597 therapeutic agent Drugs 0.000 claims description 3
- UCMIRNVEIXFBKS-UHFFFAOYSA-N beta-alanine Chemical compound NCCC(O)=O UCMIRNVEIXFBKS-UHFFFAOYSA-N 0.000 claims description 2
- 239000000126 substance Substances 0.000 claims 1
- 150000001875 compounds Chemical class 0.000 abstract description 17
- 239000002253 acid Substances 0.000 abstract description 5
- 125000005907 alkyl ester group Chemical group 0.000 abstract description 3
- 208000007882 Gastritis Diseases 0.000 abstract description 2
- 208000007107 Stomach Ulcer Diseases 0.000 abstract description 2
- 201000005917 gastric ulcer Diseases 0.000 abstract 1
- MWYHLEQJTQJHSS-UHFFFAOYSA-N tomelukast Chemical compound C1=CC(C(C)=O)=C(O)C(CCC)=C1OCCCCC1=NNN=N1 MWYHLEQJTQJHSS-UHFFFAOYSA-N 0.000 abstract 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 10
- 208000025865 Ulcer Diseases 0.000 description 9
- 230000000694 effects Effects 0.000 description 9
- 231100000397 ulcer Toxicity 0.000 description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 8
- 229940126062 Compound A Drugs 0.000 description 7
- 238000007654 immersion Methods 0.000 description 6
- NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 description 5
- 210000002784 stomach Anatomy 0.000 description 5
- 206010002091 Anaesthesia Diseases 0.000 description 4
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Chemical compound 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 4
- 241001465754 Metazoa Species 0.000 description 4
- 230000037005 anaesthesia Effects 0.000 description 4
- 239000002775 capsule Substances 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- 230000027119 gastric acid secretion Effects 0.000 description 4
- 210000004051 gastric juice 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
- 241000700159 Rattus Species 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 206010042220 Stress ulcer Diseases 0.000 description 3
- 239000001913 cellulose Substances 0.000 description 3
- 229920002678 cellulose Polymers 0.000 description 3
- 208000000718 duodenal ulcer Diseases 0.000 description 3
- 239000008187 granular material Substances 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 230000000144 pharmacologic effect Effects 0.000 description 3
- 238000005303 weighing Methods 0.000 description 3
- 229920002261 Corn starch Polymers 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 210000001015 abdomen Anatomy 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 229940084030 carboxymethylcellulose calcium Drugs 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 239000008120 corn starch Substances 0.000 description 2
- PAFZNILMFXTMIY-UHFFFAOYSA-N cyclohexylamine Chemical compound NC1CCCCC1 PAFZNILMFXTMIY-UHFFFAOYSA-N 0.000 description 2
- 210000004211 gastric acid Anatomy 0.000 description 2
- 230000000762 glandular Effects 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical compound CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 description 2
- 230000001629 suppression Effects 0.000 description 2
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- AHLPHDHHMVZTML-BYPYZUCNSA-N L-Ornithine Chemical compound NCCC[C@H](N)C(O)=O AHLPHDHHMVZTML-BYPYZUCNSA-N 0.000 description 1
- 239000004201 L-cysteine Substances 0.000 description 1
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- HTLZVHNRZJPSMI-UHFFFAOYSA-N N-ethylpiperidine Chemical compound CCN1CCCCC1 HTLZVHNRZJPSMI-UHFFFAOYSA-N 0.000 description 1
- AHLPHDHHMVZTML-UHFFFAOYSA-N Orn-delta-NH2 Natural products NCCCC(N)C(O)=O AHLPHDHHMVZTML-UHFFFAOYSA-N 0.000 description 1
- UTJLXEIPEHZYQJ-UHFFFAOYSA-N Ornithine Natural products OC(=O)C(C)CCCN UTJLXEIPEHZYQJ-UHFFFAOYSA-N 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 241000700157 Rattus norvegicus Species 0.000 description 1
- 230000007059 acute toxicity Effects 0.000 description 1
- 231100000403 acute toxicity Toxicity 0.000 description 1
- 125000005036 alkoxyphenyl group Chemical group 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 235000001014 amino acid Nutrition 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 230000003042 antagnostic effect Effects 0.000 description 1
- 230000000767 anti-ulcer Effects 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 125000004494 ethyl ester group Chemical group 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 210000001156 gastric mucosa Anatomy 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 239000003721 gunpowder Substances 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 150000002617 leukotrienes Chemical class 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 150000004702 methyl esters Chemical class 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 229960003104 ornithine Drugs 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 210000001187 pylorus Anatomy 0.000 description 1
- 230000000452 restraining effect Effects 0.000 description 1
- DCKVNWZUADLDEH-UHFFFAOYSA-N sec-butyl acetate Chemical compound CCC(C)OC(C)=O DCKVNWZUADLDEH-UHFFFAOYSA-N 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 235000011121 sodium hydroxide Nutrition 0.000 description 1
- 210000001562 sternum Anatomy 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 238000004448 titration Methods 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 230000002747 voluntary effect Effects 0.000 description 1
- 238000005550 wet granulation Methods 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
Description
【発明の詳細な説明】
する。本発明医薬の有効成分は、下記一般式(I)で示
される 5−置換テトラゾールまたは 3−置換−α−
アミノプロピオン酸、そのエステルまたは非毒性塩であ
る。[Detailed Description of the Invention] The active ingredient of the pharmaceutical of the present invention is 5-substituted tetrazole or 3-substituted-α- represented by the following general formula (I).
Aminopropionic acid, its esters or non-toxic salts.
(式中2mは3または4
nは0または1
または2−アミノ−2−カルホキ
を意味する)
一般式(INK包含される化合物中2代表的なものは以
下の通りである。(In the formula, 2m means 3 or 4, and n means 0 or 1 or 2-amino-2-calhoki) General formula (Two representative compounds among the compounds included in INK are as follows.
5−[4−(4−アセチル−3−ヒドロキシ−2−プロ
ピルフェノキシ)ブチルコテトラゾール(化合物A)
S−[3−(4−アセチル−3−ヒドロキシ−2−プロ
ピルフェノキシ)プロピル]−L−システィン(化合物
B)
5−[3−(4−アセチル−3−ヒドロキシ−2−プロ
ピルフェノキシ)プロピルコテトラゾール
5−[3−(4−アセチル−3−ヒドロキシ−2−プロ
ピルフェノキシ)プロピルチオコテトラゾール
S−[4−(4−アセチル−3−ヒドロキシ−2−プロ
ピルフェノキシ)ブチル]−L−システィン
化合物(I)のエステルは、(I)式中カルボキシ基を
有する化合物のエステルであって、たとえば低級アルキ
ルエステル(メチルエステル、エチル エステル、フロ
ビルエステル、ブチルエステル等)、アルコキシフェニ
ル低級アルキルエステル(p−エトキシベンジルエステ
ル、p−へブチルオキシベンジル エステル等)が挙げ
られる。5-[4-(4-acetyl-3-hydroxy-2-propylphenoxy)butylcotetrazole (compound A) S-[3-(4-acetyl-3-hydroxy-2-propylphenoxy)propyl]-L- Cysteine (Compound B) 5-[3-(4-acetyl-3-hydroxy-2-propylphenoxy)propylcotetrazole 5-[3-(4-acetyl-3-hydroxy-2-propylphenoxy)propylthiocotetrazole The ester of S-[4-(4-acetyl-3-hydroxy-2-propylphenoxy)butyl]-L-cysteine compound (I) is an ester of a compound having a carboxy group in the formula (I), for example Examples include lower alkyl esters (methyl ester, ethyl ester, flobyl ester, butyl ester, etc.) and alkoxyphenyl lower alkyl esters (p-ethoxybenzyl ester, p-hebutyloxybenzyl ester, etc.).
また、非毒性塩としては、塩基または酸との塩である。In addition, non-toxic salts include salts with bases or acids.
塩基との塩としては、たとえばナトリウム、カリウムな
どの無機塩基との塩、エチルアミン、プロピルアミン、
N−エチルピペリジン、ジェタノールアミン、シクロヘ
キシルアミンなどの有機塩基との塩、リジン、オルニチ
ン等の塩基性アミノ酸との塩、アンモニウム塩等であり
、また、酸との塩としては、塩酸、硫酸。Examples of salts with bases include salts with inorganic bases such as sodium and potassium, ethylamine, propylamine,
Salts with organic bases such as N-ethylpiperidine, jetanolamine, and cyclohexylamine, salts with basic amino acids such as lysine and ornithine, ammonium salts, and salts with acids include hydrochloric acid and sulfuric acid.
リン酸、臭化水素酸などの鉱酸塩である。Mineral acid salts such as phosphoric acid and hydrobromic acid.
(従来の技術)
同公報にはこれらの化合物の医薬としての有用性につい
て、ロイコトリエン拮抗作用を有し、アレルギー性疾患
の治療剤であることが記載されている。(Prior Art) Regarding the usefulness of these compounds as medicines, the publication describes that they have leukotriene antagonistic activity and are therapeutic agents for allergic diseases.
(解決しようとする問題点および解決手段)本発明者等
は、上記一般式(1)で示される5−置換テトラゾール
または 3−置換−α−アミノプロピオン酸、そのエス
テルまたは非毒性塩の薬理活性を検討したところ2 こ
れらの化合物が胃酸分泌の抑制、エタノール潰瘍の抑制
、水浸拘束ストレス潰瘍の抑制等の作用を有し、しかも
毒性がきわめて低いことが判明した。(Problems to be Solved and Means for Solving) The present inventors have discovered that the pharmacological activity of the 5-substituted tetrazole or 3-substituted-α-aminopropionic acid represented by the above general formula (1), its ester or non-toxic salt is 2 It was found that these compounds have effects such as suppressing gastric acid secretion, suppressing ethanol ulcers, and suppressing water immersion restraint stress ulcers, and have extremely low toxicity.
つぎに、有効成分についてその薬理作用を実験方法と共
に説明する。Next, the pharmacological effects of the active ingredients will be explained along with experimental methods.
(1) 胃酸分泌九対する作用
実1験方法:
Wistar系雄性ラット(体重200g前後を用い、
H,5hay等の方法[Gastroenterolo
gy+ 5+ 43(1945)]に従い、24時間絶
食後エーテル軽麻酔下で開腹し、幽門部を結紮した。結
紮後直ちに開腹し、4時間後に動物を深麻酔により殺し
。(1) Experimental method for effect on gastric acid secretion: Male Wistar rats (weighing around 200 g were used,
H, 5hay et al. [Gastroenterolo
After fasting for 24 hours, the abdomen was opened under light anesthesia with ether, and the pyloric region was ligated according to [Gy+ 5+ 43 (1945)]. Immediately after ligation, the abdomen was opened, and 4 hours later, the animals were sacrificed by deep anesthesia.
胃液を採取した。Gastric juice was collected.
胃液量を測定後、胃液中の酸濃度は自動滴定装置(平沼
産業、 Comtite−7)を用1.−. pH7,
0までの滴定に要する0、05N苛性ソーダ水溶液の量
から計算した。胃酸分泌量は胃酸濃度と胃液量の積で表
わした。試験化合物は幽門結紮の1時間前に経口投与し
た。After measuring the amount of gastric juice, the acid concentration in the gastric juice was determined using an automatic titrator (Hiranuma Sangyo, Comtite-7). −. pH7,
It was calculated from the amount of 0.05N caustic soda aqueous solution required for titration to 0. Gastric acid secretion was expressed as the product of gastric acid concentration and gastric juice volume. Test compounds were administered orally 1 hour before pylorus ligation.
試験結果: 胃酸分泌に対する本発明化合物Aの作用を表1に示す。Test results: Table 1 shows the effect of Compound A of the present invention on gastric acid secretion.
表1
コントロール −17318,5±39.3
−化合物 A 30 10 263.8±1
7.8 17.2100 10 168.0±
40.1 47.3300 7 47.3±
6.0 85.1本発明化合物Aは1101rr/k
g以上で用量依存的にう7トの胃酸分泌を抑制し、コン
トロール群に対する抑制率ハ100111g/kgで4
73%、 3oorr1g/kgで85,1%であった
( ED、o= 103.9 mg/kg )。Table 1 Control -17318,5±39.3
-Compound A 30 10 263.8±1
7.8 17.2100 10 168.0±
40.1 47.3300 7 47.3±
6.0 85.1 Compound A of the present invention is 1101rr/k
7 g/kg or more, the secretion of gastric acid in the body was dose-dependently suppressed, and the suppression rate compared to the control group was 100,111 g/kg or more.
73% and 85.1% at 3oorr1g/kg (ED, o=103.9mg/kg).
(2) エタノール潰瘍に対する作用実験方法:
Wigtar系雄性ラット(体重200g前後)を用い
、24時間絶食18時間絶水後、無水エタノールを1m
t/ラットの割合で経口投与した。1時間後に動物を深
麻酔により殺し、胃を摘出した。(2) Effect of ethanol on ulcer Experimental method: Using male Wigtar rats (weighing around 200 g), after fasting for 24 hours and water for 18 hours, 1 m of absolute ethanol was administered.
It was administered orally at a ratio of t/rat. One hour later, the animals were sacrificed by deep anesthesia and the stomachs were removed.
胃を大溝側に沿って切り開き、腺胃部粘膜に発生した潰
瘍面積を計測し、その総和を潰瘍係数(mm2)とした
。試験化合物は、無水エタノール投与の1時間前に経口
投与した。The stomach was cut open along the major groove side, and the area of ulcers generated on the glandular gastric mucosa was measured, and the sum total was defined as the ulcer coefficient (mm2). Test compounds were administered orally 1 hour before absolute ethanol administration.
実験結果:
本発明化合物へのエタノール潰瘍(て対する効果?表2
に示した。Experimental results: Effect of the compound of the present invention on ethanol ulcers (Table 2)
It was shown to.
表2
フントロール − 5 55.0±6.
9−化合物A 3 5 40.8±9725
.810 5 25.6±4.2 53.530 5
14.0±5.8 73.5100 5 3.
0±2.] 94.5本発明化合物Aは10,30
オよびlooIIIg/kgで、用量依存的にう7トの
エタノール潰瘍を抑制しy ”D5G値は9.6 mg
7kgであった。Table 2 Funtrol - 5 55.0±6.
9-Compound A 3 5 40.8±9725
.. 810 5 25.6±4.2 53.530 5
14.0±5.8 73.5100 5 3.
0±2. ] 94.5 Compound A of the present invention is 10.30
D5G value was 9.6 mg.
It weighed 7 kg.
(3) 水浸拘束ストレス潰瘍に対する作用実験方法
:
高木らの方法 [高木敬次部ら、 Jap、J、Pha
r−macol、、 18. 9 (1968)コに従
い2体重40g前後のICR系雄性マウスを拘束金網ケ
ージに入れ。(3) Effect experimental method on water immersion restraint stress ulcers: Takagi et al.'s method [Takagi Keijibe et al., Jap, J., Pha.
r-macol,, 18. 9 (1968), two male ICR mice weighing approximately 40 g were placed in a restraining wire mesh cage.
水浸23℃の水槽中に胸骨下縁まで浸し7時間放置した
。その後動物を深麻酔で殺し、胃を摘出した。胃を大溝
側に沿って切り開き、腺胃部に発生した潰瘍面積を計測
し、その総和な潰瘍係数(mrn2)とした。試験化合
物は水浸60分前に経口投与した。The animal was immersed in water up to the lower edge of the sternum in a water tank at 23°C and left for 7 hours. The animals were then killed under deep anesthesia and the stomachs were removed. The stomach was cut open along the major groove side, and the area of ulcers occurring in the glandular stomach was measured, and the total ulcer coefficient (mrn2) was determined. Test compounds were orally administered 60 minutes before water immersion.
実験結果:
本発明化合物Bの水浸拘束ストレス潰瘍に対する作用を
表3に示した。Experimental results: Table 3 shows the effect of the compound B of the present invention on water immersion restraint stress ulcers.
表3
コントロール − 5 90±14
−化合物B30 5Z2±1.3 75.6本発
明化合物Bは3011]g/kgでマウスの水浸拘束ス
トレスを抑制し、コントロール群に対する抑制率は75
.6%であった。Table 3 Control - 5 90±14
-Compound B30 5Z2±1.3 75.6 Compound B of the present invention suppressed water immersion restraint stress in mice at 3011]g/kg, and the suppression rate compared to the control group was 75
.. It was 6%.
(効果)
以上の薬理試験の結果より2本発明の有効成分は、抗潰
瘍作用を有することが明らかであり。(Effect) From the results of the above pharmacological tests, it is clear that the two active ingredients of the present invention have anti-ulcer effects.
胃潰瘍、胃炎などの消化器系疾患の治療および予防に有
効な消化器系疾患治療剤である。It is a therapeutic agent for digestive system diseases that is effective in treating and preventing digestive system diseases such as gastric ulcers and gastritis.
本発明医薬の臨床的応用としては、自体公知の薬学的に
許容されうる担体、賦形剤などと混合した医薬組成物[
例:錠剤、カプセル、散剤。For clinical application of the pharmaceutical of the present invention, a pharmaceutical composition mixed with known pharmaceutically acceptable carriers, excipients, etc. [
Examples: tablets, capsules, powders.
顆粒剤、火剤]として主として経口的に安全に投与する
ことができる。投与量は投与対象、投与ルート、症状な
どによっても異なるが2通常成人1人当り50〜1,0
OOff@であり、これを1日2〜3回に分けて経口投
与する。つぎに処方例を示す。It can be safely administered mainly orally as granules and gunpowder. The dosage varies depending on the subject, route of administration, symptoms, etc.2, but is usually 50 to 1,0 per adult.
OOff@, which is orally administered in 2 to 3 divided doses a day. Next, a prescription example is shown.
(錠剤)
式CI+の化合物 39mg乳
糖 104mg
コーンスターチ 57ff1gヒド
ロキシグロビルセルロース 4mgカルボキ
シメチルセルロースカルシウム 41T1gステ
アリン酸マグネシウム 1■計
200 fl1g式+I+の化合物
30g、乳糖104g及びコーンスターチ57gを均一
に混合し、この混合物にヒドロキシグロビルセルロース
10%(w/v ) 水溶液4゜mlを加え、湿式造粒
法により顆粒を調製した。(Tablet) Compound of formula CI+ 39mg milk
Sugar 104mg
Corn starch 57ff1g Hydroxyglobil cellulose 4mg Carboxymethyl cellulose calcium 41T1g Magnesium stearate 1■Total
200 fl1g 30 g of the compound of formula +I+, 104 g of lactose and 57 g of corn starch were uniformly mixed, 4 mm of a 10% (w/v) hydroxyglobil cellulose aqueous solution was added to this mixture, and granules were prepared by wet granulation.
この顆粒にカルボキシメチルセルロースカルシウム4g
及びステアリン酸マグネシウム1gを加えて混合したの
ちこれを圧縮打錠して錠剤(1錠200 mg )とし
た。4g of carboxymethyl cellulose calcium in this granule
After adding and mixing 1 g of magnesium stearate, the mixture was compressed into tablets (200 mg per tablet).
処方例 2
(カプセル剤)
式(I)の化合物 30mg結晶セ
ルロース 40fl1g結晶乳糖
129rq計
200 mg上記各成分の1 、OO0倍
量をとの、常法により混合したのちゼラチンカプセルに
充填しカプセル剤(1カプセル200 ff1g )と
した。Formulation example 2 (capsule) Compound of formula (I) 30mg crystalline cellulose 40fl1g crystalline lactose
129 rq meter
200 mg of each of the above ingredients was mixed in a conventional manner with 100 times the amount, and then filled into gelatin capsules to prepare capsules (1 capsule 200 ff1g).
手続補正書
昭和62年8月を日
2、発明の名称 消化器系疾患治療剤3、補正をする
者
事件との関係 特許出願人
住 所 東京都中央区日本橋本町2丁目3番11号名
称 (667)山之内製薬株式会社
代表者森岡茂夫
4、代理人
住 所 東京都板橋区小豆沢1丁目1番8号山之内製
薬株式会社 特許部内
自発
(1)明細書第7頁末行の「水浸」を「水温」に補正す
る。Procedural amendment dated August 2, 1988; Name of the invention: Digestive system disease treatment agent 3; Relationship with the person making the amendment; Patent applicant address: 2-3-11 Nihonbashi Honmachi, Chuo-ku, Tokyo Name ( 667) Yamanouchi Pharmaceutical Co., Ltd. Representative Shigeo Morioka 4, Agent Address 1-1-8 Azukizawa, Itabashi-ku, Tokyo Yamanouchi Pharmaceutical Co., Ltd. Voluntary initiative within the Patent Department (1) "Water immersion" at the end of page 7 of the specification Correct to "water temperature".
(2)明細書第8頁下から5行の「レスを抑制」を「レ
ス潰瘍を抑制」に補正する。(2) In the 5th line from the bottom of page 8 of the specification, "Suppress Ress ulcers" is corrected to "Suppress Ress ulcers."
(3)明細書第8頁下から4行に続けて2行を改めて以
下の章句を挟入する。(3) Insert the following passage in two new lines following the fourth line from the bottom of page 8 of the specification.
「(4)毒性
本発明医薬の有効成分をラットの腹腔内に投与した場合
の急性毒性L D、oは、つぎの通りである。(4) Toxicity The acute toxicity LD,o when the active ingredient of the pharmaceutical of the present invention is administered intraperitoneally to rats is as follows.
化合物A 312.5■/kg化合物B
) 1,000 mg/kg j(4)
明細書第10頁下から3行のl’−1,000倍量を
との」を[1,000倍量をとり」に補正する。Compound A 312.5■/kg Compound B
) 1,000 mg/kg j (4)
In the third line from the bottom of page 10 of the specification, "1,000 times the amount is taken as l'-1" is corrected to "take the 1,000 times amount."
Claims (1)
キシエチル基 を意味する。) で示される5−置換テトラゾールまたは3−置換−α−
アミノプロピオン酸、そのエステルまたは非毒性塩を有
効成分とする消化器系疾患治療剤[Claims] General formula ▲ Numerical formulas, chemical formulas, tables, etc. ) 5-substituted tetrazole or 3-substituted -α-
A therapeutic agent for digestive system diseases containing aminopropionic acid, its ester or non-toxic salt as an active ingredient
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP8359287A JPS63250322A (en) | 1987-04-03 | 1987-04-03 | Remedy for alimentary disease |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP8359287A JPS63250322A (en) | 1987-04-03 | 1987-04-03 | Remedy for alimentary disease |
Publications (1)
Publication Number | Publication Date |
---|---|
JPS63250322A true JPS63250322A (en) | 1988-10-18 |
Family
ID=13806759
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP8359287A Pending JPS63250322A (en) | 1987-04-03 | 1987-04-03 | Remedy for alimentary disease |
Country Status (1)
Country | Link |
---|---|
JP (1) | JPS63250322A (en) |
-
1987
- 1987-04-03 JP JP8359287A patent/JPS63250322A/en active Pending
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP3667381B2 (en) | Antipyretic analgesic | |
EP0550083B1 (en) | Medicaments for treating inflammatory conditions or for analgesia containing a NSAID and ranitidine bismuth citrate | |
US4952410A (en) | Pharmaceutical products of moxonidine and hydrochlorothiazide | |
JPH0140009B2 (en) | ||
US5416105A (en) | Treating an arteriosclerosis with glimepiride | |
HU200684B (en) | Process for producing pharmaceutical composition comprising comt inhibitor as active ingredient and active on gastrointestinal tract | |
JP3982889B2 (en) | Pharmaceutical preparations containing ibuprofen | |
EP0017169B1 (en) | Improved anti-inflammatory combinations having reduced ulcerogenicity | |
JPS63250322A (en) | Remedy for alimentary disease | |
JP4203170B2 (en) | Pharmaceutical composition | |
JP3254712B2 (en) | Pharmaceutical composition | |
JP2900056B2 (en) | Pharmaceutical composition for prevention of gastric diseases caused by nonsteroidal anti-inflammatory drugs | |
KR970006083B1 (en) | A pharmaceutical composition for treating gastrointestinal disorders | |
KR950005869B1 (en) | Therapeutic agent for gastritis | |
RU2121347C1 (en) | Medicinal preparation | |
JPS638372A (en) | Remedy for gastritis | |
KR960011773B1 (en) | Pharmaceutical compositions for the gastric ulcer prevention and therapy | |
CA1227136A (en) | Pharmaceutical compositions containing 4-(benzofuran- 2-yl)4-oxo buten-2-oic acid and/or one of the pharmaceutically acceptable salts thereof as an active ingredient | |
JPS634806B2 (en) | ||
RU2264814C2 (en) | Antihistamine pharmaceutical composition | |
JPH02200634A (en) | Antipeptic ulcer and anti-gastritis agent | |
IE43955B1 (en) | Pharmaceutical composition and dosage units thereof | |
FR2515037A1 (en) | AS MEDICINES, CERTAIN MONO-SUBSTITUTED DERIVATIVES OF 4-PHENYL 4-OXO BUTEN-2-OIC ACID, AND THE COMPOSITIONS CONTAINING SAME | |
JPS634807B2 (en) | ||
JPS6241206B2 (en) |