JP2832726B2 - Pharmaceutical composition for suppressing gastrointestinal motility - Google Patents
Pharmaceutical composition for suppressing gastrointestinal motilityInfo
- Publication number
- JP2832726B2 JP2832726B2 JP1202557A JP20255789A JP2832726B2 JP 2832726 B2 JP2832726 B2 JP 2832726B2 JP 1202557 A JP1202557 A JP 1202557A JP 20255789 A JP20255789 A JP 20255789A JP 2832726 B2 JP2832726 B2 JP 2832726B2
- Authority
- JP
- Japan
- Prior art keywords
- acid
- gastrointestinal motility
- pharmaceutical composition
- active ingredient
- dione
- 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.)
- Expired - Lifetime
Links
- 230000005176 gastrointestinal motility Effects 0.000 title claims description 12
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 6
- 239000004480 active ingredient Substances 0.000 claims description 17
- 239000000126 substance Substances 0.000 claims description 11
- ASNFTDCKZKHJSW-REOHCLBHSA-N Quisqualic acid Chemical compound OC(=O)[C@@H](N)CN1OC(=O)NC1=O ASNFTDCKZKHJSW-REOHCLBHSA-N 0.000 claims description 8
- RPXVIAFEQBNEAX-UHFFFAOYSA-N 6-Cyano-7-nitroquinoxaline-2,3-dione Chemical compound N1C(=O)C(=O)NC2=C1C=C([N+](=O)[O-])C(C#N)=C2 RPXVIAFEQBNEAX-UHFFFAOYSA-N 0.000 claims description 5
- ASNFTDCKZKHJSW-UHFFFAOYSA-N DL-Quisqualic acid Natural products OC(=O)C(N)CN1OC(=O)NC1=O ASNFTDCKZKHJSW-UHFFFAOYSA-N 0.000 claims description 4
- 229940122459 Glutamate antagonist Drugs 0.000 claims description 4
- YEUPBRRGMWBCEB-UHFFFAOYSA-N dnqx Chemical compound O=C1C(=O)N=C2C=C([N+]([O-])=O)C([N+](=O)[O-])=CC2=N1 YEUPBRRGMWBCEB-UHFFFAOYSA-N 0.000 claims description 4
- HCZHHEIFKROPDY-UHFFFAOYSA-N kynurenic acid Chemical group C1=CC=C2NC(C(=O)O)=CC(=O)C2=C1 HCZHHEIFKROPDY-UHFFFAOYSA-N 0.000 claims description 4
- VLSMHEGGTFMBBZ-OOZYFLPDSA-M Kainate Chemical compound CC(=C)[C@H]1C[NH2+][C@H](C([O-])=O)[C@H]1CC([O-])=O VLSMHEGGTFMBBZ-OOZYFLPDSA-M 0.000 claims description 3
- HOKKHZGPKSLGJE-GSVOUGTGSA-N N-Methyl-D-aspartic acid Chemical compound CN[C@@H](C(O)=O)CC(O)=O HOKKHZGPKSLGJE-GSVOUGTGSA-N 0.000 claims description 3
- HOKKHZGPKSLGJE-UHFFFAOYSA-N N-methyl-D-aspartic acid Natural products CNC(C(O)=O)CC(O)=O HOKKHZGPKSLGJE-UHFFFAOYSA-N 0.000 claims description 3
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 3
- 239000003825 glutamate receptor antagonist Substances 0.000 claims description 3
- 238000000034 method Methods 0.000 claims description 3
- HCMBCMVOCRJSME-SCSAIBSYSA-N (2r)-2-amino-5-oxo-5-(sulfomethylamino)pentanoic acid Chemical compound OC(=O)[C@H](N)CCC(=O)NCS(O)(=O)=O HCMBCMVOCRJSME-SCSAIBSYSA-N 0.000 claims description 2
- WDVICMJSSBICSA-UHFFFAOYSA-N 1-(4-bromobenzoyl)piperazine-2,3-dicarboxylic acid Chemical compound OC(=O)C1C(C(=O)O)NCCN1C(=O)C1=CC=C(Br)C=C1 WDVICMJSSBICSA-UHFFFAOYSA-N 0.000 claims description 2
- ACIJGUBIMXQCMF-SCSAIBSYSA-N D-gamma-Glu-Gly Chemical compound OC(=O)[C@H](N)CCC(=O)NCC(O)=O ACIJGUBIMXQCMF-SCSAIBSYSA-N 0.000 claims description 2
- GHFJNBYZGVNAOV-UHFFFAOYSA-N Stizolobinate Chemical compound OC(=O)C(N)CC1=CC=C(C(O)=O)OC1=O GHFJNBYZGVNAOV-UHFFFAOYSA-N 0.000 claims description 2
- 210000005036 nerve Anatomy 0.000 claims description 2
- 235000019260 propionic acid Nutrition 0.000 claims description 2
- 230000004936 stimulating effect Effects 0.000 claims description 2
- CVOFKRWYWCSDMA-UHFFFAOYSA-N 2-chloro-n-(2,6-diethylphenyl)-n-(methoxymethyl)acetamide;2,6-dinitro-n,n-dipropyl-4-(trifluoromethyl)aniline Chemical compound CCC1=CC=CC(CC)=C1N(COC)C(=O)CCl.CCCN(CCC)C1=C([N+]([O-])=O)C=C(C(F)(F)F)C=C1[N+]([O-])=O CVOFKRWYWCSDMA-UHFFFAOYSA-N 0.000 claims 1
- 150000001875 compounds Chemical class 0.000 claims 1
- DUWWHGPELOTTOE-UHFFFAOYSA-N n-(5-chloro-2,4-dimethoxyphenyl)-3-oxobutanamide Chemical compound COC1=CC(OC)=C(NC(=O)CC(C)=O)C=C1Cl DUWWHGPELOTTOE-UHFFFAOYSA-N 0.000 claims 1
- 230000000694 effects Effects 0.000 description 4
- 230000002401 inhibitory effect Effects 0.000 description 4
- 210000002784 stomach Anatomy 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 150000003839 salts Chemical class 0.000 description 3
- 230000002269 spontaneous effect Effects 0.000 description 3
- 208000004998 Abdominal Pain Diseases 0.000 description 2
- 206010012735 Diarrhoea Diseases 0.000 description 2
- 102000018899 Glutamate Receptors Human genes 0.000 description 2
- 108010027915 Glutamate Receptors Proteins 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 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
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- 208000008469 Peptic Ulcer Diseases 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 208000037656 Respiratory Sounds Diseases 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 206010047924 Wheezing Diseases 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 2
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 230000003088 neuroexcitatory effect Effects 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- RWVIMCIPOAXUDG-UHFFFAOYSA-N 6,7-dinitro-1,4-dihydroquinoxaline-2,3-dione Chemical compound N1C(=O)C(=O)NC2=C1C=C([N+](=O)[O-])C([N+]([O-])=O)=C2 RWVIMCIPOAXUDG-UHFFFAOYSA-N 0.000 description 1
- 206010000087 Abdominal pain upper Diseases 0.000 description 1
- 206010051290 Central nervous system lesion Diseases 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- JOYRKODLDBILNP-UHFFFAOYSA-N Ethyl urethane Chemical compound CCOC(N)=O JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 206010020852 Hypertonia Diseases 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- 235000019759 Maize starch Nutrition 0.000 description 1
- 229940121948 Muscarinic receptor antagonist Drugs 0.000 description 1
- 241000700157 Rattus norvegicus Species 0.000 description 1
- KQZBVNZAEQASKU-UHFFFAOYSA-N Stizolobate Chemical compound OC(=O)C(N)CC=1C=C(C(O)=O)OC(=O)C=1 KQZBVNZAEQASKU-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical class CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 1
- 210000001015 abdomen Anatomy 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 235000011054 acetic acid Nutrition 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 150000001447 alkali salts Chemical class 0.000 description 1
- VLSMHEGGTFMBBZ-UHFFFAOYSA-N alpha-Kainic acid Natural products CC(=C)C1CNC(C(O)=O)C1CC(O)=O VLSMHEGGTFMBBZ-UHFFFAOYSA-N 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 239000003194 amino acid receptor blocking agent Substances 0.000 description 1
- 230000003042 antagnostic effect Effects 0.000 description 1
- 239000002249 anxiolytic agent Substances 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 239000000812 cholinergic antagonist Substances 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 210000003191 femoral vein Anatomy 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000007902 hard capsule Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- VLSMHEGGTFMBBZ-OOZYFLPDSA-N kainic acid Chemical compound CC(=C)[C@H]1CN[C@H](C(O)=O)[C@H]1CC(O)=O VLSMHEGGTFMBBZ-OOZYFLPDSA-N 0.000 description 1
- 229950006874 kainic acid Drugs 0.000 description 1
- 229940080428 lactose 200 mg Drugs 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 239000007923 nasal drop Substances 0.000 description 1
- 229940100662 nasal drops Drugs 0.000 description 1
- 230000001537 neural effect Effects 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 208000011906 peptic ulcer disease Diseases 0.000 description 1
- 230000002688 persistence Effects 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 230000003248 secreting effect Effects 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000000829 suppository 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
- 239000003826 tablet Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 230000001515 vagal effect Effects 0.000 description 1
Landscapes
- Quinoline Compounds (AREA)
- Pyrane Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Description
【発明の詳細な説明】 ［産業上の利用分野］ 本発明は、新規な消化管運動抑制用医薬組成物に関す
る。Description: TECHNICAL FIELD The present invention relates to a novel pharmaceutical composition for suppressing gastrointestinal motility.
［発明の背景］ 消化管運動機能異常としては、ストレスや中枢神経の
病変に伴なう迷走神経の過緊張など、過度の神経的緊張
により神経性に消化管の運動機能や分泌機能を異常に亢
進させ、腹痛、腹鳴、下痢、消化性潰瘍等を引き起こす
ことが知られている。BACKGROUND OF THE INVENTION Gastrointestinal motility abnormalities include abnormal nervous motor and secretory functions caused by excessive neural tone, such as vagal hypertonia associated with stress and central nervous system lesions. It is known to cause aggravation, causing abdominal pain, wheezing, diarrhea, peptic ulcer and the like.
これらに対する治療は、通常マイナートランキライザ
ーや抗コリン剤等が使用されてきたが、副作用の頻度が
高く、必ずしも満足できるものとは言えない。Usually, a minor tranquilizer, an anticholinergic agent, and the like have been used for the treatment of these, but the frequency of side effects is high, and it cannot be said that the treatment is always satisfactory.
本発明者らは、グルタミン酸拮抗剤であって、且つ、
グルタミン酸受容体の活性物質であるＮ−メチル−Ｄ−
アスパラギン酸、キスカル酸及びカイニン酸の神経興奮
作用をいずれも抑制し得る非選択的な拮抗様式の物質
が、優れた消化管運動抑制作用を有することを見出し本
発明を完成した。The present inventors are glutamate antagonists, and
N-methyl-D-, an active substance of glutamate receptor
The present inventors have found that a nonselective antagonistic substance capable of suppressing all of the neuroexcitatory effects of aspartic acid, quisqualic acid, and kainate has an excellent gastrointestinal motility inhibitory effect, and completed the present invention.
グルタミン酸受容体に関与する物質については種々の
検討がなされているが、これらの物質が消化管運動に対
して作用を及ぼすことは全く知られていない。Various studies have been made on substances involved in the glutamate receptor, but it is not known that these substances have any effect on gastrointestinal motility.
［問題点を解決するための手段］ 本発明は、グルタミン酸拮抗剤であって且つＮ−メチ
ル−Ｄ−アスパラギン酸、キスカル酸及びカイニン酸に
よる神経興奮作用を非選択的に抑制し得る物質を有効成
分として含有することを特徴とする消化管運動抑制用医
薬組成物である。[Means for Solving the Problems] The present invention provides a substance which is a glutamate antagonist and is capable of non-selectively suppressing the neuroexcitatory action of N-methyl-D-aspartic acid, quisqualic acid and kainate. It is a pharmaceutical composition for suppressing gastrointestinal motility, characterized in that it is contained as a component.
本発明における有効成分は、グルタミン酸拮抗剤であ
って、且つ、Ｎ−メチル−Ｄ−アスパラギン酸、キスカ
ル酸及びカイニン酸等による神経興奮作用を抑制し得る
物質である。（R.L.Johnsonら、Journal of Medicinal
Chemistry,1988,vol.31,No.11,p,2057−2066及び、J.C.
Watkins,Neurotox′88:Molecular Basis of Drug ＆ Pe
sticide Action,p.445−459参照）。本発明における有
効成分はこのような性質を有するものであればよいが、
特に好ましい物質の例としては、 ４−ヒドロキシ−２−キノリンカルボン酸、 6,7−ジニトロキノキサリン−2,3−ジオン（互変異性
体、2,3−ジヒドロキシ−6,7−ジニトロキノキサリ
ン）、 ６−シアノ−７−ニトロキノキサリン−2,3−ジオン
（互変異性体、６−シアノ−2,3−ジヒドロキシ−７−
ニトロキノキサリン）、 １−（ｐ−ブロモベンゾイル）ピペラジン−2,3−ジ
カルボン酸、 ２−アミノ−３−（６−カルボキシ−２−オキソ−2H
−ピラン−４−イル）プロパン酸、 ２−アミノ−３−（６−カルボキシ−２−オキソ−2H
−ピラン−３−イル）プロパン酸、 γ−Ｄ−グルタミルアミノメチルスルホン酸、及びγ
−Ｄ−グルタミルグリシンを挙げることができる。The active ingredient in the present invention is a substance that is a glutamate antagonist and is capable of suppressing the nerve stimulating action of N-methyl-D-aspartic acid, quisqualic acid, kainic acid, and the like. (RL Johnson et al., Journal of Medicinal
Chemistry, 1988, vol. 31, No. 11, p, 2057-2066 and JC
Watkins, Neurotox'88: Molecular Basis of Drug & Pe
sticide Action, pp. 445-459). The active ingredient in the present invention may be one having such properties,
Examples of particularly preferred substances are 4-hydroxy-2-quinolinecarboxylic acid, 6,7-dinitroquinoxaline-2,3-dione (tautomer, 2,3-dihydroxy-6,7-dinitroquinoxaline), 6-cyano-7-nitroquinoxaline-2,3-dione (tautomer, 6-cyano-2,3-dihydroxy-7-
Nitroquinoxaline), 1- (p-bromobenzoyl) piperazine-2,3-dicarboxylic acid, 2-amino-3- (6-carboxy-2-oxo-2H
-Pyran-4-yl) propanoic acid, 2-amino-3- (6-carboxy-2-oxo-2H
-Pyran-3-yl) propanoic acid, γ-D-glutamylaminomethylsulfonic acid, and γ
-D-glutamylglycine.
本発明における有効成分は、遊離体の形であってもよ
く、また、その薬理学的に許容され得る塩であってもよ
い。このような塩としては、無機酸（例、塩酸、硫酸、
燐酸）又は有機酸（例、酢酸、プロピオン酸、クエン
酸、酒石酸、リンゴ酸、シュウ酸、メタンスルホン酸）
等の塩のような酸付加塩や、ナトリウム塩、カリウム
塩、トリエチルアミン塩等のような塩基性塩が挙げられ
る。The active ingredient in the present invention may be in a free form or a pharmacologically acceptable salt thereof. Such salts include inorganic acids (eg, hydrochloric acid, sulfuric acid,
Phosphoric acid) or organic acids (eg, acetic acid, propionic acid, citric acid, tartaric acid, malic acid, oxalic acid, methanesulfonic acid)
And the like, and basic salts such as sodium salt, potassium salt, triethylamine salt and the like.
本発明における有効成分は公知の物質であり、それ自
体公知の方法により製造したり入手することができる。
例えば、４−ヒドロキシ−２−キノリンカルボン酸はWa
ld,Joullie,J.Org,Chem.31,3369（1966）、6,7−ジニト
ロキノキサリン−2,3−ジオンは東京学芸大学紀要 第
４部門、1981年、33巻、p.115−118、そして、６−シア
ノ−７−ニトロキノキサリン−2,3−ジオンは特開昭63
−83074号公報等に記載の方法により得られる。しかし
ながら、これらの物質が消化管運動抑制作用を有し消化
管運動抑制用医薬組成物の有効成分として有用であるこ
とについては知られていない。The active ingredient in the present invention is a known substance, and can be produced or obtained by a method known per se.
For example, 4-hydroxy-2-quinolinecarboxylic acid is Wa
ld, Joullie, J. Org, Chem. 31 , 3369 (1966), 6,7-dinitroquinoxaline-2,3-dione is the fourth bulletin of the bulletin of Tokyo Gakugei University, 1981, vol. 33, pp. 115-118, 6-cyano-7-nitroquinoxaline-2,3-dione is disclosed in
It can be obtained by the method described in JP-A-83074. However, it has not been known that these substances have a gastrointestinal motility inhibitory action and are useful as an active ingredient of a pharmaceutical composition for gastrointestinal motility suppression.
本発明における有効成分が優れた消化管運動抑制作用
を有することを下記の実験により示す。The following experiment shows that the active ingredient in the present invention has an excellent gastrointestinal motility inhibitory action.
［実験方法］ Wistar系雄性ラットを24時間絶食し、ウレタン（1.2g
/kg,s.c.）で麻酔した。腹部を正中線に沿って切開して
胃を露出させ、前胃に小孔を開け、小バルーンを挿入し
た。バルーンに5cmH2Oの圧負荷をかけ、15〜30分間放置
したのち、胃の自発運動をバルーンの内圧変化として圧
トランジューサーを介して測定した。[Experimental method] Male Wistar rats were fasted for 24 hours and urethane (1.2 g)
/ kg, sc). The abdomen was incised along the midline to expose the stomach, a stoma was opened in the forestomach, and a small balloon was inserted. After applying a pressure load of 5 cmH 2 O to the balloon and allowing it to stand for 15 to 30 minutes, the spontaneous movement of the stomach was measured as a change in the internal pressure of the balloon via a pressure transducer.
薬物（上記有効成分）は、生理食塩液に溶解し、NaOH
でpHを７に調整したのち、大腿静脈より投与した。The drug (active ingredient) is dissolved in physiological saline and NaOH
After adjusting the pH to 7, the solution was administered through the femoral vein.
［実験成績］ 本発明の有効成分は、いずれも低用量で胃の自発運動
を抑制させた。胃の自発運動を抑制させるための最小有
効量は、下記第１表に示す通りであった。 第 １ 表 有効成分 最小有効量（mg/kg,i,v.） Ａ 2.0 Ｂ 0.5 Ｃ ＜1.0 A:4−ヒドロキシ−２−キノリンカルボン酸、 B:6,7−ジニトロキノキサリン−2,3−ジオン、 C:6−シアノ−７−ニトロキノキサリン−2,3−ジオン、 本発明の有効成分である前記物質は、優れた消化管運
動抑制作用を有しており、腹痛、腹鳴、胃痙攣、下痢、
消化性潰瘍などの治療剤として優れた効能を有する。[Experimental results] The active ingredients of the present invention all suppressed spontaneous movement of the stomach at a low dose. The minimum effective dose for suppressing the spontaneous movement of the stomach was as shown in Table 1 below. Table 1 Active ingredient Minimum effective dose (mg / kg, i, v.) A 2.0 B 0.5 C <1.0 A: 4-hydroxy-2-quinoline carboxylic acid, B: 6,7-dinitroquinoxaline-2,3- Dione, C: 6-cyano-7-nitroquinoxaline-2,3-dione, The substance, which is an active ingredient of the present invention, has an excellent gastrointestinal motility inhibitory action, and has abdominal pain, wheezing, gastric spasm, diarrhea,
It has excellent efficacy as a therapeutic agent for peptic ulcers.
また、本発明の有効成分は、その効果の持続性が優れ
ており、投与に伴う副作用が少ない。Further, the active ingredient of the present invention has excellent persistence of the effect, and has few side effects upon administration.
本発明の有効成分は、遊離体又はその塩として投与で
きる。その投与量は、それらの何れであっても、遊離体
の量として、経口投与において一般に1mg〜1000mg/日の
範囲の量が適当である。本発明の有効成分は、経口的に
も非経口的（例、静脈内又は皮下注射、経鼻投与、直腸
投与）にも投与される。The active ingredient of the present invention can be administered as a free form or a salt thereof. Regardless of the dose, a dose in the range of generally 1 mg to 1000 mg / day for oral administration is appropriate as the amount of the free form. The active ingredient of the present invention is administered orally or parenterally (eg, intravenous or subcutaneous injection, nasal administration, rectal administration).
剤型としては、例えば、注射剤、坐剤、散剤、点鼻
剤、丸剤、錠剤、シロップ剤等であってよく、それ自体
公知の賦形剤、崩壊剤、結合剤、滑沢剤、コーティング
剤、基材、その他などと共に製剤できる。The dosage form may be, for example, injections, suppositories, powders, nasal drops, pills, tablets, syrups and the like, excipients known per se, disintegrants, binders, lubricants, It can be formulated together with coating agents, substrates, etc.
以下に実施例を示す。 Examples will be described below.
［実施例１］ 製剤例（錠剤） １錠（210mg）中に下記成分を含有する。[Example 1] Formulation example (tablet) One tablet (210 mg) contains the following components.
活性成分 40mg ラクトース 103mg でんぷん 50mg ステアリン酸マグネシウム 2mg ヒドロキシプロピルセルロース 15mg ［実施例２］ 製材例（カプセル剤） ゼラチン硬カプセル１球中に下記成分（330mg）を含
有する。Active ingredient 40 mg Lactose 103 mg Starch 50 mg Magnesium stearate 2 mg Hydroxypropylcellulose 15 mg [Example 2] Saw material (capsule) One gelatin hard capsule contains the following components (330 mg).
活性成分 20mg ラクトース 200mg でんぷん 70mg ポリビニルピロリドン 5mg 結晶セルロース 35mg ［実施例３］ 製剤例（顆粒） 顆粒1g中に下記成分を含有する。 Active ingredient 20 mg Lactose 200 mg Starch 70 mg Polyvinylpyrrolidone 5 mg Crystalline cellulose 35 mg [Example 3] Formulation example (granules) 1 g of granules contains the following components.
活性成分 100mg ラクトース 450mg トウモロコシデンプン 400mg ヒドロキシプロピルセルロース 50mg Active ingredient 100mg Lactose 450mg Maize starch 400mg Hydroxypropyl cellulose 50mg
───────────────────────────────────────────────────── フロントページの続き (51)Int.Cl.6 識別記号 ＦＩ Ａ６１Ｋ 31/495 Ａ６１Ｋ 31/495 38/00 37/02 (58)調査した分野(Int.Cl.6，ＤＢ名) A61K 45/00 A61K 31/35 A61K 31/47 A61K 31/495 A61K 31/255 A61K 31/195 A61K 37/02 ＣＡ（ＳＴＮ) ＲＥＧＩＳＴＲＹ（ＳＴＮ) ＷＰＩＤＳ（ＳＴＮ)──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. 6 identification code FI A61K 31/495 A61K 31/495 38/00 37/02 (58) Fields surveyed (Int.Cl. 6 , DB name) A61K 45 / 00 A61K 31/35 A61K 31/47 A61K 31/495 A61K 31/255 A61K 31/195 A61K 37/02 CA (STN) REGISTRY (STN) WPIDS (STN)
Claims (2)
ル−Ｄ−アスパラギン酸、キスカル酸及びカイニン酸に
よる神経興奮作用を非選択的に抑制し得る物質を有効成
分として含有することを特徴とする消化管運動抑制用医
薬組成物。1. A substance which is a glutamate antagonist and which can non-selectively inhibit the nerve stimulating action of N-methyl-D-aspartic acid, quisqualic acid and kainate as an active ingredient. A pharmaceutical composition for suppressing gastrointestinal motility.
カルボン酸、6,7−ジニトロキノキサリン−2,3−ジオ
ン、６−シアノ−７−ニトロキノキサリン−2,3−ジオ
ン、１−（ｐ−ブロモベンゾイル）ピペラジン−2,3−
ジカルボン酸、２−アミノ−３−（６−カルボキシ−２
−オキソ−2H−ピラン−４−イル）プロパン酸、２−ア
ミノ−３−（６−カルボキシ−２−オキソ−2H−ピラン
−３−イル）プロパン酸、γ−Ｄ−グルタミルアミノメ
チルスルホン酸、及びγ−Ｄ−グルタミルグリシンから
なる群から選択された化合物であることを特徴とする請
求項第１項記載の消化管運動抑制用医薬組成物。2. The method according to claim 1, wherein said substance is 4-hydroxy-2-quinoline carboxylic acid, 6,7-dinitroquinoxaline-2,3-dione, 6-cyano-7-nitroquinoxaline-2,3-dione, 1- ( (p-Bromobenzoyl) piperazine-2,3-
Dicarboxylic acid, 2-amino-3- (6-carboxy-2)
-Oxo-2H-pyran-4-yl) propanoic acid, 2-amino-3- (6-carboxy-2-oxo-2H-pyran-3-yl) propanoic acid, γ-D-glutamylaminomethylsulfonic acid, The pharmaceutical composition for suppressing gastrointestinal motility according to claim 1, which is a compound selected from the group consisting of and γ-D-glutamylglycine.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP1202557A JP2832726B2 (en) | 1989-08-03 | 1989-08-03 | Pharmaceutical composition for suppressing gastrointestinal motility |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP1202557A JP2832726B2 (en) | 1989-08-03 | 1989-08-03 | Pharmaceutical composition for suppressing gastrointestinal motility |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH0366627A JPH0366627A (en) | 1991-03-22 |
| JP2832726B2 true JP2832726B2 (en) | 1998-12-09 |
Family
ID=16459472
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP1202557A Expired - Lifetime JP2832726B2 (en) | 1989-08-03 | 1989-08-03 | Pharmaceutical composition for suppressing gastrointestinal motility |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP2832726B2 (en) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP4736268B2 (en) * | 2001-08-09 | 2011-07-27 | 東洋紡績株式会社 | Gas processing apparatus and gas processing method |
| US6986901B2 (en) | 2002-07-15 | 2006-01-17 | Warner-Lambert Company Llc | Gastrointestinal compositions |
| WO2006025551A1 (en) * | 2004-08-30 | 2006-03-09 | Takeda Pharmaceutical Company Limited | Screening method |
-
1989
- 1989-08-03 JP JP1202557A patent/JP2832726B2/en not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| JPH0366627A (en) | 1991-03-22 |
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