JPH0381219A - Remedy for gastric mucosal disorder - Google Patents
Remedy for gastric mucosal disorderInfo
- Publication number
- JPH0381219A JPH0381219A JP21794389A JP21794389A JPH0381219A JP H0381219 A JPH0381219 A JP H0381219A JP 21794389 A JP21794389 A JP 21794389A JP 21794389 A JP21794389 A JP 21794389A JP H0381219 A JPH0381219 A JP H0381219A
- Authority
- JP
- Japan
- Prior art keywords
- gastric mucosal
- taurine
- ammonia
- remedy
- active ingredient
- 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
- 230000002496 gastric effect Effects 0.000 title claims abstract description 30
- XOAAWQZATWQOTB-UHFFFAOYSA-N taurine Chemical compound NCCS(O)(=O)=O XOAAWQZATWQOTB-UHFFFAOYSA-N 0.000 claims abstract description 46
- 229960003080 taurine Drugs 0.000 claims abstract description 23
- 239000004480 active ingredient Substances 0.000 claims abstract description 11
- 239000003814 drug Substances 0.000 claims description 11
- 229940124597 therapeutic agent Drugs 0.000 claims description 9
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 abstract description 36
- 229910021529 ammonia Inorganic materials 0.000 abstract description 18
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 18
- 230000000694 effects Effects 0.000 abstract description 8
- 208000028867 ischemia Diseases 0.000 abstract description 6
- 206010019280 Heart failures Diseases 0.000 abstract description 3
- 208000027119 bilirubin metabolic disease Diseases 0.000 abstract description 3
- 230000004217 heart function Effects 0.000 abstract description 3
- 208000036796 hyperbilirubinemia Diseases 0.000 abstract description 3
- 230000003908 liver function Effects 0.000 abstract description 3
- 206010023129 Jaundice cholestatic Diseases 0.000 abstract 1
- 201000005267 Obstructive Jaundice Diseases 0.000 abstract 1
- 230000001747 exhibiting effect Effects 0.000 abstract 1
- 230000005764 inhibitory process Effects 0.000 abstract 1
- 208000035475 disorder Diseases 0.000 description 16
- 241000590002 Helicobacter pylori Species 0.000 description 8
- 210000002784 stomach Anatomy 0.000 description 8
- 208000007882 Gastritis Diseases 0.000 description 7
- 102000003896 Myeloperoxidases Human genes 0.000 description 6
- 108090000235 Myeloperoxidases Proteins 0.000 description 6
- 230000017531 blood circulation Effects 0.000 description 6
- 208000025865 Ulcer Diseases 0.000 description 5
- 210000004369 blood Anatomy 0.000 description 5
- 239000008280 blood Substances 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 5
- 231100000397 ulcer Toxicity 0.000 description 5
- 210000000440 neutrophil Anatomy 0.000 description 4
- 241000700159 Rattus Species 0.000 description 3
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 239000004202 carbamide Substances 0.000 description 3
- 210000001156 gastric mucosa Anatomy 0.000 description 3
- 241000167854 Bourreria succulenta Species 0.000 description 2
- 229920002261 Corn starch Polymers 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- 208000007107 Stomach Ulcer Diseases 0.000 description 2
- OUUQCZGPVNCOIJ-UHFFFAOYSA-M Superoxide Chemical compound [O-][O] OUUQCZGPVNCOIJ-UHFFFAOYSA-M 0.000 description 2
- 102000019197 Superoxide Dismutase Human genes 0.000 description 2
- 108010012715 Superoxide dismutase Proteins 0.000 description 2
- 108010046334 Urease Proteins 0.000 description 2
- 210000000941 bile Anatomy 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- 235000019693 cherries Nutrition 0.000 description 2
- 239000008120 corn starch Substances 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000000796 flavoring agent Substances 0.000 description 2
- 235000013355 food flavoring agent Nutrition 0.000 description 2
- 235000003599 food sweetener Nutrition 0.000 description 2
- 201000005917 gastric ulcer Diseases 0.000 description 2
- 210000001035 gastrointestinal tract Anatomy 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
- 239000000463 material Substances 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 230000000414 obstructive effect Effects 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 239000002504 physiological saline solution Substances 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 230000037390 scarring Effects 0.000 description 2
- 229910052717 sulfur Inorganic materials 0.000 description 2
- 239000003765 sweetening agent Substances 0.000 description 2
- 244000215068 Acacia senegal Species 0.000 description 1
- 229920001817 Agar Polymers 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
- 206010002091 Anaesthesia Diseases 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- 240000004160 Capsicum annuum Species 0.000 description 1
- 235000008534 Capsicum annuum var annuum Nutrition 0.000 description 1
- 235000007862 Capsicum baccatum Nutrition 0.000 description 1
- QDHHCQZDFGDHMP-UHFFFAOYSA-N Chloramine Chemical compound ClN QDHHCQZDFGDHMP-UHFFFAOYSA-N 0.000 description 1
- JOYRKODLDBILNP-UHFFFAOYSA-N Ethyl urethane Chemical compound CCOC(N)=O JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 1
- 206010061164 Gastric mucosal lesion Diseases 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- 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 1
- 244000246386 Mentha pulegium Species 0.000 description 1
- 235000016257 Mentha pulegium Nutrition 0.000 description 1
- 235000004357 Mentha x piperita Nutrition 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 229920000881 Modified starch Polymers 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 102000004316 Oxidoreductases Human genes 0.000 description 1
- 108090000854 Oxidoreductases Proteins 0.000 description 1
- 229920001800 Shellac Polymers 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
- 229930006000 Sucrose Natural products 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- WBWWGRHZICKQGZ-UHFFFAOYSA-N Taurocholic acid Natural products OC1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(=O)NCCS(O)(=O)=O)C)C1(C)C(O)C2 WBWWGRHZICKQGZ-UHFFFAOYSA-N 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- 108010093894 Xanthine oxidase Proteins 0.000 description 1
- 102100033220 Xanthine oxidase Human genes 0.000 description 1
- 210000001015 abdomen Anatomy 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 239000000205 acacia gum Substances 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-N acrylic acid group Chemical group C(C=C)(=O)O NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 239000012752 auxiliary agent Substances 0.000 description 1
- 244000309466 calf Species 0.000 description 1
- 239000001728 capsicum frutescens Substances 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 230000001364 causal effect Effects 0.000 description 1
- 239000007958 cherry flavor Substances 0.000 description 1
- 235000019416 cholic acid Nutrition 0.000 description 1
- 239000002812 cholic acid derivative Substances 0.000 description 1
- 150000001842 cholic acids Chemical class 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 208000023652 chronic gastritis Diseases 0.000 description 1
- 230000037326 chronic stress Effects 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 231100000433 cytotoxic Toxicity 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 238000006114 decarboxylation reaction Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 238000007323 disproportionation reaction Methods 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 230000000857 drug effect Effects 0.000 description 1
- 208000000718 duodenal ulcer Diseases 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 210000003191 femoral vein Anatomy 0.000 description 1
- 235000010855 food raising agent Nutrition 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 238000012812 general test Methods 0.000 description 1
- 235000001050 hortel pimenta Nutrition 0.000 description 1
- QWPPOHNGKGFGJK-UHFFFAOYSA-N hypochlorous acid Chemical compound ClO QWPPOHNGKGFGJK-UHFFFAOYSA-N 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000008595 infiltration Effects 0.000 description 1
- 238000001764 infiltration Methods 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000000302 ischemic effect Effects 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- XMGQYMWWDOXHJM-UHFFFAOYSA-N limonene Chemical compound CC(=C)C1CCC(C)=CC1 XMGQYMWWDOXHJM-UHFFFAOYSA-N 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- 239000003094 microcapsule Substances 0.000 description 1
- 210000004400 mucous membrane Anatomy 0.000 description 1
- 210000004165 myocardium Anatomy 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 231100000957 no side effect Toxicity 0.000 description 1
- 239000007968 orange flavor Substances 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 230000007310 pathophysiology Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 210000001539 phagocyte Anatomy 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
- 230000010410 reperfusion Effects 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 229940081974 saccharin Drugs 0.000 description 1
- 235000019204 saccharin Nutrition 0.000 description 1
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 239000004208 shellac Substances 0.000 description 1
- ZLGIYFNHBLSMPS-ATJNOEHPSA-N shellac Chemical compound OCCCCCC(O)C(O)CCCCCCCC(O)=O.C1C23[C@H](C(O)=O)CCC2[C@](C)(CO)[C@@H]1C(C(O)=O)=C[C@@H]3O ZLGIYFNHBLSMPS-ATJNOEHPSA-N 0.000 description 1
- 229940113147 shellac Drugs 0.000 description 1
- 235000013874 shellac Nutrition 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 230000035882 stress Effects 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 238000012353 t test Methods 0.000 description 1
- WBWWGRHZICKQGZ-GIHLXUJPSA-N taurocholic acid Chemical compound C([C@@H]1C[C@H]2O)[C@@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@@H]([C@@H](CCC(=O)NCCS(O)(=O)=O)C)[C@@]2(C)[C@H](O)C1 WBWWGRHZICKQGZ-GIHLXUJPSA-N 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
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- 229940116362 tragacanth Drugs 0.000 description 1
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Abstract
Description
【発明の詳細な説明】
本発明は、タウリンを有効成分とする胃粘膜障害治療剤
に関する。DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a therapeutic agent for gastric mucosal disorders containing taurine as an active ingredient.
近年、腸管が虚血状態に陥ると、スーパーオキシドアニ
オン（０）及び過酸化水素（口２０２）の生成、並びに
ミエロペルオキシダーゼ（ＭＰＯ）の活性が増大し、そ
れらが細胞障害性に作用することが報告されている。例
えば、０」、グランジャーら（＾ｃｔａ Ｐｈｙｓｉｏ
ｌ ５ｃａｎｄ １９８Ｂ、 ５ｕｐｐ１．５４８：４
７〜６３〉は、小腸において虚血再潅流（１ｓｃｈｅｉ
ｉａ −ｒｅｐｅｒｆｕｓｉｏｎ）下にキサンチンオキ
シダーゼが活性化され、増加したＯ旦が粘膜の微小循環
系を障害することを報告している。In recent years, it has been shown that when the intestinal tract becomes ischemic, the production of superoxide anion (0) and hydrogen peroxide (202) and the activity of myeloperoxidase (MPO) increase, which can have a cytotoxic effect. It has been reported. For example, 0'', Granger et al.
l 5cand 198B, 5upp1.548:4
7-63> ischemia reperfusion (1 schei
It has been reported that xanthine oxidase is activated under (ia-reperfusion), and the increased oxygen impairs the mucosal microcirculatory system.
一方、Ｏ；の別の発生源として、好中球由来のＮ＾ＤＰ
Ｈオキシダーゼからの経路が重要視されている。０５は
不均化又はスーパーオキシドジスムターゼ（ＳＯＤ）の
触媒作用によって口２０２に変化するが、その後、Ｈ２
Ｏ２は好中球のミエロペルオキシダーゼ（ＭＰＯ）の存
在下にて（ｌ の酸化を引き起し、次亜塩素酸（口０
ＣＪ）を生成することが証明されている（Ｃ，Ｓ、フー
トら、Ｎａｔｕｒｅ ３０１．７１５ （１９８３）
） 。胃を含む消化管粘膜固有層には、好中球を含む食
細胞が多く存在し、前記ＭＰＯの存在が報告されている
。口ＯＣｆは、反応性が強く、生体においてはアンモニ
アと反応して強力な細胞障害性を示すクロラミン（ＮＨ
２Ｏ〉となり組織障害性を発揮する。On the other hand, N^DP derived from neutrophils is another source of O;
The pathway from H oxidase is emphasized. 05 is transformed into 202 by dismutation or superoxide dismutase (SOD) catalysis, but then H2
In the presence of neutrophil myeloperoxidase (MPO), O2 causes the oxidation of (L) and hypochlorous acid (MPO).
(C, S, Foote et al., Nature 301.715 (1983)
). The lamina propria of the gastrointestinal tract, including the stomach, contains many phagocytes including neutrophils, and the presence of the MPO has been reported. OCf is highly reactive and contains chloramine (NH), which reacts with ammonia and exhibits strong cytotoxicity in living organisms.
2O〉 and exhibits tissue-damaging properties.
近年、キャンピロバクター・ピロリ（鉦肚ｕ虹ｂａＣｔ
ｅｒ 肛江坦）と慢性活動性胃炎、胃潰瘍、十二指腸
潰瘍との因果関係が推定されており、特に胃炎に関して
は、キャンピロバクター・ピロリがその原因であること
が証明されている（ Ｊ、 Ｒ，ナレンとＢ、Ｊ、ｖ−
シアル、 Ｌａｎｃｅｔ ｉ、 １２７３ （１９８３
））。In recent years, Campylobacter pylori
It is presumed that there is a causal relationship between chronic active gastritis, gastric ulcer, and duodenal ulcer, and Campylobacter pylori has been proven to be the cause of gastritis (J, R , Naren and B, J, v-
Sial, Lancet i, 1273 (1983
)).
ヒト胃には、０〜５０ｍＨのアンモニアの存在が認めら
れている。このアンモニアは、感染したキャンピロバク
ター・ピロリ由来のウレアーゼにより生体内の尿素から
生成されることは、キャンピロバクター・ピロリの存在
する胃にアンモニアが高いこと、キャンピロバクター・
ピロリの存在する胃に尿素を投与すると急速にアンモニ
アに変化すること等により証明されている（Ｂ、Ｊ、マ
ーシアルら、Ｌａｎｃｅｔ ｉ、 ９６５ （１９８６
））。The presence of ammonia at 0 to 50 mH is recognized in the human stomach. This ammonia is produced from urea in the body by urease derived from infected Campylobacter pylori, which means that ammonia is high in the stomach where Campylobacter pylori is present.
This has been proven by the fact that when urea is administered to the stomach where pylori is present, it rapidly changes to ammonia (B, J., Marcial et al., Lancet I, 965 (1986
)).
このように、キャンピロバクター・ピロリによる胃粘膜
障害の病態生理の一つとしてアンモニアとの関係が重要
視されており、従って、アンモニア障害を抑制する薬剤
は、臨床的に胃粘膜障害の治療剤として有用であると考
えられる。Thus, the relationship with ammonia is considered important as one of the pathophysiology of gastric mucosal disorders caused by Campylobacter pylori, and therefore, drugs that suppress ammonia disorders are clinically considered therapeutic agents for gastric mucosal disorders. It is considered to be useful as a.
本発明は、アンモニア、虚血等のストレスによる胃粘膜
障害に対して、タウリンが強力な障害抑制作用を有する
ことを見出すことによって完成されたものであり、タウ
リンを有効成分とする胃粘膜障害治療剤を提供すること
を目的としている。The present invention was completed by discovering that taurine has a strong inhibitory effect on gastric mucosal disorders caused by stress such as ammonia and ischemia, and provides treatment for gastric mucosal disorders using taurine as an active ingredient. The aim is to provide a drug.
タウリンは、仔牛の胆汁中から発見されたと言われる含
硫アミノ酸（２−アミノエタンスルホンＭ）で、ヒトを
含め各種動物の体内に存在し、生体内ではシスティン酸
の脱炭酸によって生成される。Taurine is a sulfur-containing amino acid (2-aminoethanesulfone M) said to have been discovered in the bile of calves, and is present in the bodies of various animals, including humans, and is produced in vivo by decarboxylation of cystic acid.
特に心筋内に最も豊富に存在すると言われ、胆汁中では
各種のコール酸と縮合した形態のタウロコール酸として
存在している。タウリンのしＤ５ｏ値は約７０００■／
旬以上（マウス経口）であり、極めて低毒性の物質であ
る。In particular, it is said to be most abundant in the myocardium, and in bile it is present in the form of taurocholic acid condensed with various cholic acids. Taurine's D5o value is approximately 7000■/
It is a substance that is more than suitable for use (orally administered to mice) and has extremely low toxicity.
タウリンは、従来、口内性心不全に対する心機能の改善
剤及び高ビリルビン血症（閉塞性黄痕を除く）における
肝機能の改善剤として使用されてきたが、本発明の如き
胃粘膜障害に対する障害抑制作用については全く知られ
ていなかった。Taurine has conventionally been used as an agent for improving cardiac function in oral heart failure and as an agent for improving liver function in hyperbilirubinemia (excluding obstructive yellow scarring), but taurine has been used as an agent for improving cardiac function in cases of oral heart failure and as an agent for improving liver function in hyperbilirubinemia (excluding obstructive yellow scarring). Nothing was known about its effects.
本発明は、タウリンを有効成分とする胃粘膜障害治療剤
を提供するものである。The present invention provides a therapeutic agent for gastric mucosal disorders containing taurine as an active ingredient.
本発明における「胃粘膜障害」とは、胃炎及び胃潰瘍を
示し、より詳細には、胃炎はキャンピロバクター・ピロ
リに感染した好中球浸潤の強い活動性慢性胃炎、慢性ス
トレス胃炎及び急性胃炎を示す。 さらにまた、本発明
の胃粘膜障害治療剤は上記の胃粘膜障害に対する予防薬
として使用することも可能である。In the present invention, "gastric mucosal disorder" refers to gastritis and gastric ulcer, and more specifically, gastritis includes active chronic gastritis with strong neutrophil infiltration infected with Campylobacter pylori, chronic stress gastritis, and acute gastritis. show. Furthermore, the therapeutic agent for gastric mucosal disorders of the present invention can also be used as a prophylactic agent against the above-mentioned gastric mucosal disorders.
本発明の胃粘膜障害治療剤の有効成分であるタウリンの
有効使用量は１〜５０００■、好ましくは５〜１５００
Ｒｇの範囲である。The effective amount of taurine, which is the active ingredient of the therapeutic agent for gastric mucosal disorders of the present invention, is 1 to 5000 μl, preferably 5 to 1500 μl.
This is the range of Rg.
この有効成分は、例えば、錠剤、カプセル剤、エリキシ
ル剤、マイクロカプセル剤又は懸濁液剤の形態で使用し
得る。The active ingredient can be used, for example, in the form of tablets, capsules, elixirs, microcapsules or suspensions.
本発明の有効成分として使用するタウリンは、胃粘膜障
害の治療や予防を必要とする患者に対して、患者当たり
５〜１５００１１ｇの用量範囲で一般に数回に分けて１
日当たり２０〜２００００１１ｇの全日用量で経口投与
することができる。タウリンの投与量は病気の重さ、患
者の体重及び当業者が認めるその他の因子によって変化
させることができる。The taurine used as the active ingredient of the present invention is generally administered in doses ranging from 5 to 150,011 g per patient in several doses for patients who require treatment or prevention of gastric mucosal disorders.
It can be administered orally at a total daily dose of 20-2000011 g per day. The dosage of taurine can vary depending on the severity of the disease, the weight of the patient, and other factors recognized by those skilled in the art.
本発明の胃粘膜障害治療剤の有効成分として使用するタ
ウリン、医薬上許容し得るタウリンの塩又はこれらの混
和物的５〜１５００Ｒｇは、医薬上許容し得るベヒクル
、担体、賦形剤、結合剤、防腐剤、安定剤、香味剤など
とともに一般的に認められた製薬実施に要求される単位
用量形態で混和される。Taurine, a pharmaceutically acceptable salt of taurine, or a mixture of 5 to 1,500 Rg thereof used as an active ingredient in the therapeutic agent for gastric mucosal disorders of the present invention may be present in a pharmaceutically acceptable vehicle, carrier, excipient, or binder. , preservatives, stabilizers, flavoring agents, etc., in unit dosage form as required by generally accepted pharmaceutical practice.
これらの組成物又は製剤における活性物質の量は、指示
された範囲の適当な用量が得られるように決められる。The amount of active substance in these compositions or preparations is determined to provide a suitable dosage within the indicated range.
錠剤、カプセル剤などに混和することができる具体的な
助剤は以下に示すものである。トラガント、アラビアゴ
ム、コーンスターチ又はゼラチンのような結合剤：微品
性セルロースのような賦形剤：コーンスターチ、前ゼラ
チン化デンプン、アルギン酸などのような膨化剤；ステ
アリン酸マグネシウムのような潤滑剤：ショ糖、乳糖又
はサッカリンのような甘味剤：ペパーミント、アカモノ
油又はチェリーのような香味剤。調剤単位形態がカプセ
ルである場合には、上記のタイプの材料にさらに油脂の
ような液状担体を含有させることができる。種々の他の
材料も、被覆剤として、又は調剤単位の物理的形態を別
の方法で変化させるために存在させることができる。例
えば、錠剤はシェラツク、砂糖又はその両方で被覆する
ことができる。シロップ又はエリキシルは、活性化合物
、甘味剤としてショ糖、防腐剤としてメチルパラベン及
びプロピルパラベン、色素並びにチェリー又はオレンジ
香味のような香味剤を含有させ得る。Specific auxiliary agents that can be mixed into tablets, capsules, etc. are shown below. Binders such as tragacanth, gum arabic, corn starch or gelatin; Excipients such as microcellulose; Leavening agents such as corn starch, pre-gelatinized starch, alginic acid etc.; Lubricants such as magnesium stearate: Sweetening agents such as sugar, lactose or saccharin; Flavoring agents such as peppermint, red pepper oil or cherry. When the dosage unit form is a capsule, materials of the above type can further include a liquid carrier such as an oil or fat. Various other materials can also be present as coatings or to otherwise modify the physical form of the dosage unit. For example, tablets may be coated with shellac, sugar or both. A syrup or elixir may contain the active compound, sucrose as a sweetening agent, methyl and propylparabens as preservatives, a dye and flavoring, such as cherry or orange flavor.
本発明の胃粘膜障害治療剤は、タウリンを有効成分とす
るために、副作用がほとんどなく大量投与が可能である
だけでなく、虚血、アンモニアなどに起因する胃粘膜障
害の抑制に顕著な効果を有している。Since the therapeutic agent for gastric mucosal disorders of the present invention contains taurine as an active ingredient, it not only has almost no side effects and can be administered in large quantities, but also has remarkable effects on suppressing gastric mucosal disorders caused by ischemia, ammonia, etc. have.
以下の実施例によって、本発明をさらに具体的に説明す
る。The present invention will be explained in more detail with reference to the following examples.
実施例
２４時時間量のＳＤ系雄性ラット（２５０ｇ）をウレタ
ン麻酔下にて用い −、Ａ、マーセリューら（ａａｓｔ
ｒｏｅｎｔｅｒｏ＋ｏｏｙ ６４．１１３０〜１１３５
（１９７３））の方法に従ってｉｎ ＶｉｔｒＯチェン
バー（Ｃ’ｈａｌｂｅｉｒ）を作製した。即ち、ラット
腹部を正中切開した後、胃を引出し、血管神経を温存し
、前背部より胃体部にかけてＩｎし、アクリル製チェン
バーに固定した。Example 2 A 4-hour dose of SD male rats (250 g) was used under urethane anesthesia.
roentero+ooy 64.1130-1135
(1973)) in VitrO chambers (C'halbeir) were prepared. That is, after making a midline incision in the rat's abdomen, the stomach was pulled out, the vascular nerves were preserved, the stomach was injected from the anterior dorsal region to the body of the stomach, and the stomach was fixed in an acrylic chamber.
チェンバー内の胃粘膜は２ｍの生理食塩水で満タシ、胃
粘膜電位差（ｐｏｔｅｎｔｉａｌ ｄｉＮｅｒｅｎｃｅ
）及び胃粘膜血流（ｂｌｏｏｄ ｆｌｏｗ）を連続測定
した。胃粘膜電位差測定は、アガーブリッジを用い、関
電極はチェンバー内に、不関電極は皮下に設置しミリボ
ルトメーターにて連続測定した。また胃粘膜血流測定は
、レーザー血流計（Ｐｅｒｉｆｌｕｘ）を用い、チェン
バー上から、定位固定装置（Ｎａｒｉｓｉｇｅ）にてブ
０−べを粘膜面に直角にあてて測定した。なお、得られ
た結果の平均値は、５ｔｕｄｅｎｔ’ｓ−ｔ ｔｅｓｔ
にて比較検討した。The gastric mucosa in the chamber was filled with 2 m of physiological saline, and the gastric mucosal potential difference (potential diNerence)
) and gastric mucosal blood flow were continuously measured. The gastric mucosal potential difference was measured using an agar bridge, with the interested electrode placed in the chamber and the indifferent electrode subcutaneously, and continuous measurement was made with a millivoltmeter. Gastric mucosal blood flow was measured using a laser blood flow meter (Periflux) by placing a probe perpendicular to the mucosal surface from above the chamber with a stereotaxic device (Narisige). The average value of the obtained results is 5student's-t test
A comparative study was conducted.
胃粘膜電位差及び胃粘膜血流が安定した後、胃粘膜障害
治療剤の薬剤効果に関する一般的な試験方法に基づいて
以下の実験を行った。After the gastric mucosal potential difference and gastric mucosal blood flow were stabilized, the following experiment was conducted based on a general test method for the drug effect of a therapeutic agent for gastric mucosal disorders.
（Ｂ） アンモニア−虚血モデルに対するタラッ
ト大腿静脈より脱血を行い、胃粘膜血流を低下させ、３
０ｍＨアンモニア（生理食塩水中〉をチェンバー内に投
与し、投与後１時間後までの胃粘膜電位差及び胃粘膜血
流を測定した。アンモニア投与１時間後、実態顕微鏡に
て、赤色に変化した胃粘膜部分の面積を測定し、潰瘍係
数（単位間２〉とした。(B) In the ammonia-ischemia model, blood was removed from the Talat femoral vein to reduce gastric mucosal blood flow;
0 mH ammonia (in physiological saline) was administered into the chamber, and the gastric mucosal potential difference and gastric mucosal blood flow were measured up to 1 hour after administration.1 hour after ammonia administration, gastric mucosa that had turned red was observed using a stereoscopic microscope. The area of the part was measured and defined as an ulcer coefficient (unit interval 2).
一方、２５０ ｉＭタウリン２ｄをチェンバー内に３０
分前に投与した群に対し同様の脱血及びアンモニア投与
を行い、その効果を観察した。On the other hand, add 30 iM taurine 2d to the chamber.
Similar blood removal and ammonia administration were performed for the group that had been administered minutes before, and the effects were observed.
その結果、脱血処置を行ったラットに対し、チェンバー
内に３０ａ＋Ｈアンモニアを投与すると、胃粘膜電位差
は直ちに著明に低下、し、電位差の値は、１時間後にお
いてアンモニア投与前の値（１００％）の７２％となり
、また明らかな肉眼的胃粘膜病変が認められた。このと
き、潰瘍係数は１２．６±９．２１ｍ１＋２であった。As a result, when 30a+H ammonia was administered into the chamber of a rat that had undergone blood removal treatment, the gastric mucosal potential difference immediately decreased markedly, and after 1 hour, the value of the potential difference changed to the value before ammonia administration (100 %), and clear macroscopic gastric mucosal lesions were observed. At this time, the ulcer index was 12.6±9.21 m1+2.
これに対し、タウリン前処置群において、脱血処置及び
３０ｍＭアンモニアを投与した場合、１時間後の電位差
の低下率はアンモニア投与前の値（１００％）の１０８
％となり、また潰瘍係数は２．５±３．０層２に低下し
、肉眼的病変ともほぼ完全に抑制された。即ち、上記結
果は、虚血プラス低濃度アンモニアに起因する胃粘膜障
害が、タウリン前処置により完全に抑制されることを示
している。In contrast, in the taurine pretreatment group, when blood was removed and 30mM ammonia was administered, the rate of decrease in potential difference after 1 hour was 108% of the value (100%) before ammonia administration.
%, and the ulcer index decreased to 2.5±3.0 layer 2, and macroscopic lesions were almost completely suppressed. That is, the above results indicate that gastric mucosal damage caused by ischemia plus low concentration ammonia is completely inhibited by taurine pretreatment.
さらに別の群に対し、脱血処置並びにチェンバー内に２
００ｊｌｙ／ｄｌの尿素１ｄ及びウレアーゼ活性２００
ＩＵ／−のキャンピロバクター・ピロリ１ｄを投与し
、その後の胃粘膜の変化について検討した。In addition, another group was treated with blood removal and two
00jly/dl urea 1d and urease activity 200
IU/- of Campylobacter pylori 1d was administered, and subsequent changes in the gastric mucosa were examined.
その結果、キャンピロバクター・ピロリをチェンバー内
に投与した群において、１時間後の潰瘍係数は３２±９
ｊＩ１１２となった。一方、２５０ ｍＭタウリン２ｄ
を３０分前に前投与した群において、１時間後の潰瘍係
数は５±３ａ＃＋２となり、肉眼的胃粘膜障害に対し有
意の抑制効果が認められた。As a result, in the group in which Campylobacter pylori was administered into the chamber, the ulcer index after 1 hour was 32 ± 9.
It became jI112. Meanwhile, 250 mM taurine 2d
In the group pre-administered 30 minutes before, the ulcer index after 1 hour was 5±3a#+2, indicating a significant suppressive effect on macroscopic gastric mucosal damage.
Claims (1)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP1217943A JP2642198B2 (en) | 1989-08-24 | 1989-08-24 | Gastric mucosal disorder treatment |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP1217943A JP2642198B2 (en) | 1989-08-24 | 1989-08-24 | Gastric mucosal disorder treatment |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH0381219A true JPH0381219A (en) | 1991-04-05 |
| JP2642198B2 JP2642198B2 (en) | 1997-08-20 |
Family
ID=16712139
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP1217943A Expired - Lifetime JP2642198B2 (en) | 1989-08-24 | 1989-08-24 | Gastric mucosal disorder treatment |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP2642198B2 (en) |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1997038685A1 (en) * | 1996-04-12 | 1997-10-23 | Haeussinger Dieter | Use of an osmolyte in the preparation of a medicament for treating complications resulting from ischemia |
| US5796690A (en) * | 1994-04-26 | 1998-08-18 | Nec Corporation | Disc controller with improved data sync and re-sync mark detection |
| US5880098A (en) * | 1996-04-12 | 1999-03-09 | Pharmacia & Upjohn Aktiebolag | Therapeutic treatment |
| JPH11322617A (en) * | 1998-05-07 | 1999-11-24 | Tokiwa Yakuhin Kogyo Kk | Pharmaceutical composition for prevention and treatment of gastric ulcer, containing extract of chicken or oyster |
| JPH11343244A (en) * | 1998-03-30 | 1999-12-14 | Taisho Pharmaceut Co Ltd | Oral composition |
| EP1635799B1 (en) * | 2003-06-23 | 2009-08-05 | BELLUS Health (International) Limited | Pharmaceutical formulations of amyloid inhibiting compounds |
-
1989
- 1989-08-24 JP JP1217943A patent/JP2642198B2/en not_active Expired - Lifetime
Non-Patent Citations (2)
| Title |
|---|
| J.BIOL.CHEM.=1984 * |
| J.CLIN.MICRO.=1988 * |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5796690A (en) * | 1994-04-26 | 1998-08-18 | Nec Corporation | Disc controller with improved data sync and re-sync mark detection |
| WO1997038685A1 (en) * | 1996-04-12 | 1997-10-23 | Haeussinger Dieter | Use of an osmolyte in the preparation of a medicament for treating complications resulting from ischemia |
| US5880098A (en) * | 1996-04-12 | 1999-03-09 | Pharmacia & Upjohn Aktiebolag | Therapeutic treatment |
| JPH11343244A (en) * | 1998-03-30 | 1999-12-14 | Taisho Pharmaceut Co Ltd | Oral composition |
| JPH11322617A (en) * | 1998-05-07 | 1999-11-24 | Tokiwa Yakuhin Kogyo Kk | Pharmaceutical composition for prevention and treatment of gastric ulcer, containing extract of chicken or oyster |
| EP1635799B1 (en) * | 2003-06-23 | 2009-08-05 | BELLUS Health (International) Limited | Pharmaceutical formulations of amyloid inhibiting compounds |
| EP2127648A1 (en) * | 2003-06-23 | 2009-12-02 | BELLUS Health (International) Limited | Pharmaceutical formulations of amyloid inhibiting compounds |
Also Published As
| Publication number | Publication date |
|---|---|
| JP2642198B2 (en) | 1997-08-20 |
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