JP5857143B2 - Anti-ulcer composition - Google Patents
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- JP5857143B2 JP5857143B2 JP2015022804A JP2015022804A JP5857143B2 JP 5857143 B2 JP5857143 B2 JP 5857143B2 JP 2015022804 A JP2015022804 A JP 2015022804A JP 2015022804 A JP2015022804 A JP 2015022804A JP 5857143 B2 JP5857143 B2 JP 5857143B2
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- lactic acid
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- acid bacteria
- nsaids
- ulcer
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- 239000000203 mixture Substances 0.000 title description 10
- 230000000767 anti-ulcer Effects 0.000 title description 6
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 claims description 43
- 241000894006 Bacteria Species 0.000 claims description 23
- 239000004310 lactic acid Substances 0.000 claims description 21
- 235000014655 lactic acid Nutrition 0.000 claims description 21
- GYDJEQRTZSCIOI-LJGSYFOKSA-N tranexamic acid Chemical compound NC[C@H]1CC[C@H](C(O)=O)CC1 GYDJEQRTZSCIOI-LJGSYFOKSA-N 0.000 claims description 16
- 229960000401 tranexamic acid Drugs 0.000 claims description 16
- 239000008194 pharmaceutical composition Substances 0.000 claims description 12
- 239000003907 antipyretic analgesic agent Substances 0.000 claims description 6
- 229940121363 anti-inflammatory agent Drugs 0.000 claims description 5
- 239000002260 anti-inflammatory agent Substances 0.000 claims description 5
- 230000003110 anti-inflammatory effect Effects 0.000 claims description 3
- 230000001754 anti-pyretic effect Effects 0.000 claims description 2
- 230000003637 steroidlike Effects 0.000 claims description 2
- 230000036592 analgesia Effects 0.000 claims 1
- 239000002221 antipyretic Substances 0.000 claims 1
- CGIGDMFJXJATDK-UHFFFAOYSA-N indomethacin Chemical compound CC1=C(CC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 CGIGDMFJXJATDK-UHFFFAOYSA-N 0.000 description 16
- 230000006378 damage Effects 0.000 description 13
- 230000002496 gastric effect Effects 0.000 description 13
- 208000025865 Ulcer Diseases 0.000 description 9
- 239000003814 drug Substances 0.000 description 8
- 229960000905 indomethacin Drugs 0.000 description 8
- 231100000397 ulcer Toxicity 0.000 description 8
- 230000000694 effects Effects 0.000 description 6
- 229940079593 drug Drugs 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- 241001465754 Metazoa Species 0.000 description 4
- 241000700159 Rattus Species 0.000 description 4
- 208000027418 Wounds and injury Diseases 0.000 description 4
- 238000009472 formulation Methods 0.000 description 4
- 210000001156 gastric mucosa Anatomy 0.000 description 4
- 208000014674 injury Diseases 0.000 description 4
- 239000003826 tablet Substances 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 2
- 239000003699 antiulcer agent Substances 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 208000035475 disorder Diseases 0.000 description 2
- 239000004615 ingredient 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
- 229920000609 methyl cellulose Polymers 0.000 description 2
- 239000001923 methylcellulose Substances 0.000 description 2
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 2
- -1 sazapyrine Chemical compound 0.000 description 2
- 210000002784 stomach Anatomy 0.000 description 2
- 229940124597 therapeutic agent Drugs 0.000 description 2
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 1
- 241000193830 Bacillus <bacterium> Species 0.000 description 1
- 241000193749 Bacillus coagulans Species 0.000 description 1
- 241000186016 Bifidobacterium bifidum Species 0.000 description 1
- 241000186012 Bifidobacterium breve Species 0.000 description 1
- 101000957724 Catostomus commersonii Corticoliberin-1 Proteins 0.000 description 1
- 206010008570 Chloasma Diseases 0.000 description 1
- 229920002785 Croscarmellose sodium Polymers 0.000 description 1
- 201000004624 Dermatitis Diseases 0.000 description 1
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 1
- 206010060891 General symptom Diseases 0.000 description 1
- 208000032843 Hemorrhage Diseases 0.000 description 1
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
- HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 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
- 208000003351 Melanosis Diseases 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- SKZKKFZAGNVIMN-UHFFFAOYSA-N Salicilamide Chemical compound NC(=O)C1=CC=CC=C1O SKZKKFZAGNVIMN-UHFFFAOYSA-N 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- 229960001138 acetylsalicylic acid Drugs 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 230000003266 anti-allergic effect Effects 0.000 description 1
- 229940124599 anti-inflammatory drug Drugs 0.000 description 1
- 208000010668 atopic eczema Diseases 0.000 description 1
- 229940054340 bacillus coagulans Drugs 0.000 description 1
- 229940002008 bifidobacterium bifidum Drugs 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 208000034158 bleeding Diseases 0.000 description 1
- 230000000740 bleeding effect Effects 0.000 description 1
- 238000009395 breeding Methods 0.000 description 1
- 230000001488 breeding effect Effects 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000002537 cosmetic Substances 0.000 description 1
- 229960001681 croscarmellose sodium Drugs 0.000 description 1
- 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 description 1
- 239000000551 dentifrice Substances 0.000 description 1
- 229960001193 diclofenac sodium Drugs 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- SBNKFTQSBPKMBZ-UHFFFAOYSA-N ethenzamide Chemical compound CCOC1=CC=CC=C1C(N)=O SBNKFTQSBPKMBZ-UHFFFAOYSA-N 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 239000007902 hard capsule Substances 0.000 description 1
- 230000023597 hemostasis Effects 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- 229960001680 ibuprofen Drugs 0.000 description 1
- 238000005286 illumination Methods 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 229940066544 lactobacillus sporogenes Drugs 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 229960002373 loxoprofen Drugs 0.000 description 1
- YMBXTVYHTMGZDW-UHFFFAOYSA-N loxoprofen Chemical compound C1=CC(C(C(O)=O)C)=CC=C1CC1C(=O)CCC1 YMBXTVYHTMGZDW-UHFFFAOYSA-N 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 229960003511 macrogol Drugs 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- 229960002216 methylparaben Drugs 0.000 description 1
- 239000000820 nonprescription drug Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 150000003180 prostaglandins Chemical class 0.000 description 1
- 229960000581 salicylamide Drugs 0.000 description 1
- JGMJQSFLQWGYMQ-UHFFFAOYSA-M sodium;2,6-dichloro-n-phenylaniline;acetate Chemical compound [Na+].CC([O-])=O.ClC1=CC=CC(Cl)=C1NC1=CC=CC=C1 JGMJQSFLQWGYMQ-UHFFFAOYSA-M 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 208000003265 stomatitis Diseases 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000008399 tap water Substances 0.000 description 1
- 235000020679 tap water Nutrition 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 230000036269 ulceration Effects 0.000 description 1
- 210000001215 vagina Anatomy 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 239000008215 water for injection Substances 0.000 description 1
- 230000004584 weight gain Effects 0.000 description 1
- 235000019786 weight gain Nutrition 0.000 description 1
- 230000002087 whitening effect Effects 0.000 description 1
Description
本発明は、非ステロイド性解熱鎮痛消炎剤による胃粘膜障害を軽減した医薬組成物に関する。 The present invention relates to a pharmaceutical composition that reduces gastric mucosal damage caused by a nonsteroidal antipyretic analgesic / antiinflammatory agent.
非ステロイド性解熱鎮痛消炎剤(以下、NSAIDsと称することがある)は、プロスタグランジン生合成の抑制作用に基づく鎮痛・抗炎症・解熱作用を有する。そのため必然的に胃粘膜が障害され、潰瘍形成にいたる副作用を有することが知られている。 Non-steroidal antipyretic analgesic / anti-inflammatory agents (hereinafter sometimes referred to as NSAIDs) have analgesic / anti-inflammatory / antipyretic effects based on the inhibitory action of prostaglandin biosynthesis. Therefore, it is known that the gastric mucosa is inevitably damaged and has side effects leading to ulceration.
トラネキサム酸は、抗プラスミン剤として抗出血、抗アレルギー、抗炎症作用などを有し、出血・湿疹・口内炎・肝斑の内服治療薬として医療用医薬品(例えば、非特許文献1参照)やOTC医薬品(例えば、非特許文献2参照)で使用されている。また、止血用として薬用歯磨剤や、美白等の目的で薬用化粧品にも配合されている。 Tranexamic acid has anti-bleeding, anti-allergic, anti-inflammatory effects, etc. as an antiplasmin agent, and is a medical drug (for example, see Non-Patent Document 1) or an OTC drug as an internal medicine for bleeding, eczema, stomatitis, or melasma (See, for example, Non-Patent Document 2). It is also blended in medicated dentifrices for hemostasis and medicinal cosmetics for the purpose of whitening.
有胞子性乳酸菌は、胞子形成をした乳酸菌(Lactobacillus sporogenes)であり、嫌気性条件で乳酸菌の顔、好気性条件ではBacillus属の顔を持つユニークな菌である。分類学的にはBacillus coagulansであり(非特許文献3参照)、通常の乳酸菌と同様に整腸剤として配合されている(例えば、非特許文献2参照)。 Spore-forming lactic acid bacteria are spore-forming lactic acid bacteria (Lactobacillus sporogenes), which are unique bacteria having a lactic acid bacteria face under anaerobic conditions and a Bacillus face under aerobic conditions. Taxonomically, it is Bacillus coagulans (see Non-Patent Document 3), and is formulated as an intestinal adjuster in the same manner as ordinary lactic acid bacteria (see Non-Patent Document 2).
有胞子性乳酸菌が抗潰瘍作用を有することは知られていないが、乳酸菌12菌株について酢酸潰瘍による抗潰瘍効果を調べた結果、Bifidobacterium bifidum の1菌株とBifidobacterium breveの2菌株に抗潰瘍作用が認められたことが報告されている(非特許文献4参照)。 Although it is not known that spore-forming lactic acid bacteria have anti-ulcer activity, as a result of examining the anti-ulcer effect of acetic acid ulcer on 12 lactic acid bacteria strains, 1 strain of Bifidobacterium bifidum and 2 strains of Bifidobacterium breve have anti-ulcer activity It has been reported (see Non-Patent Document 4).
これまでに、トラネキサム酸や有胞子性乳酸菌の抗潰瘍作用は知られておらず、トラネキサム酸と有胞子性乳酸菌を配合した医薬組成物も知られていない。更に、当該配合によってNSAIDsによる胃粘膜障害が軽減されることを記載又は示唆したものは見当たらない。 Until now, the anti-ulcer action of tranexamic acid and spore-forming lactic acid bacteria has not been known, and a pharmaceutical composition containing tranexamic acid and spore-forming lactic acid bacteria has not been known. Furthermore, there is no description or suggestion that gastric mucosal damage caused by NSAIDs is reduced by the formulation.
本発明の課題はNSAIDsによる胃粘膜障害を顕著に軽減する新たな医薬組成物の提供である。 An object of the present invention is to provide a new pharmaceutical composition that significantly reduces gastric mucosal damage caused by NSAIDs.
本発明者らは鋭意研究を実施した結果、NSAIDsと有胞子性乳酸菌を併用した場合には、胃粘膜障害が増悪されること、しかし、NSAIDs、トラネキサム酸及び有胞子性乳酸菌を同時併用すると、胃粘膜障害が顕著に軽減され、潰瘍が抑制されるという驚くべき事実を見出し、本発明を完成するに至った。 As a result of intensive studies, the inventors have found that gastric mucosal damage is exacerbated when NSAIDs and spore-forming lactic acid bacteria are used in combination, but when NSAIDs, tranexamic acid and spore-forming lactic acid bacteria are used together, The inventors have found the surprising fact that gastric mucosal damage is remarkably reduced and ulcers are suppressed, and the present invention has been completed.
すなわち、本発明は、以下の(1)〜(4)を提供するものである。
(1):トラネキサム酸及び有胞子性乳酸菌を含有する医薬組成物。
(2):胃粘膜障害治療剤である(1)に記載の医薬組成物。
(3):潰瘍治療剤である(1)に記載の医薬組成物。及び、
(4):非ステロイド性解熱鎮痛消炎剤によって引き起こされる胃粘膜障害及び/又は潰瘍の治療剤である(1)〜(3)のいずれか1に記載の医薬組成物。
That is, the present invention provides the following (1) to (4).
(1): A pharmaceutical composition comprising tranexamic acid and spore-forming lactic acid bacteria.
(2): The pharmaceutical composition according to (1), which is a therapeutic agent for gastric mucosal disorder.
(3) The pharmaceutical composition according to (1), which is an ulcer treatment agent. as well as,
(4) The pharmaceutical composition according to any one of (1) to (3), which is a therapeutic agent for gastric mucosal disorder and / or ulcer caused by a nonsteroidal antipyretic analgesic / antiinflammatory agent.
非ステロイド性解熱鎮痛消炎剤(NSAIDs)を投与するにあたり、本発明のトラネキサム酸と有胞子性乳酸菌を含有する医薬組成物を併用すると、NSAIDsによる胃粘膜障害を抑制するので、抗潰瘍剤として有用である。 When administering non-steroidal antipyretic analgesic / anti-inflammatory drugs (NSAIDs), the combined use of the pharmaceutical composition containing tranexamic acid of the present invention and spore-forming lactic acid bacteria suppresses gastric mucosal damage caused by NSAIDs and is useful as an antiulcer agent. It is.
本発明のトラネキサム酸は第15改正日本薬局方に収載されており、有胞子性乳酸菌は日本薬局方外医薬品規格2002に収載されている。 Tranexamic acid of the present invention is listed in the 15th revised Japanese Pharmacopoeia, and sporic lactic acid bacteria are listed in the Japanese Pharmacopoeia Standard 2002.
本発明の組成物の1回投与量における、トラネキサム酸及び有胞子性乳酸菌の含有量は特に制限はないが、それぞれ、5〜2000mg及び0.1〜400mgで、好ましくは、それぞれ、10〜1200mg及び1〜100mgである。 The contents of tranexamic acid and spore-forming lactic acid bacteria in a single dose of the composition of the present invention are not particularly limited, but are 5 to 2000 mg and 0.1 to 400 mg, respectively, preferably 10 to 1200 mg, respectively. And 1 to 100 mg.
本発明におけるNSAIDsとしては、例えば、アスピリン、イブプロフェン、エテンザミド、ロキソプロフェンナトリウム、ジクロフェナクナトリウム、サザピリン、サリチルアミド、インドメタシン等を挙げることができる。 Examples of NSAIDs in the present invention include aspirin, ibuprofen, etenzamide, loxoprofen sodium, diclofenac sodium, sazapyrine, salicylamide, indomethacin and the like.
本発明の組成物は、常法に従って製剤されるが、投与方法に合わせて、各薬剤を別々に製剤してもよい。 The composition of the present invention is formulated according to a conventional method, but each drug may be formulated separately according to the administration method.
本発明の組成物等は、例えば、錠剤、カプセル剤、顆粒剤、散剤、液剤若しくはシロップ剤等の経口投与用組成物である。本発明の組成物には、必要に応じて、乳糖、結晶セルロース、ヒドロキシプロピルセルロース等の賦形剤、ステアリン酸マグネシウム等の滑沢剤、マクロゴール等の結合剤、クロスカルメロースナトリウム等の崩壊剤、メチルパラベン等の安定剤を適宜添加することができ、さらに、通常使用される、甘味料、酸味料、香料等の矯味矯臭剤や、希釈剤等の添加剤を用いることもできる。 The composition of the present invention is a composition for oral administration such as a tablet, capsule, granule, powder, liquid or syrup. In the composition of the present invention, if necessary, excipients such as lactose, crystalline cellulose, hydroxypropylcellulose, lubricants such as magnesium stearate, binders such as macrogol, disintegration of croscarmellose sodium and the like A stabilizer such as an agent and methylparaben can be added as appropriate, and a commonly used flavoring agent such as a sweetener, acidulant and fragrance, and an additive such as a diluent can also be used.
以下に、試験例及び製剤例を挙げて本発明を更に具体的に説明するが、本発明はこれらに限定されるものではない。 Hereinafter, the present invention will be described more specifically with reference to test examples and formulation examples, but the present invention is not limited thereto.
(製剤例1)ハードカプセル剤 (Formulation Example 1) Hard capsule
上記成分及び分量をとり、日局製剤総則「カプセル剤」の項に準じてカプセルを製造する。 Taking the above ingredients and amounts, capsules are produced according to the section “General Capsules” of the Japanese Pharmacopoeia.
(製剤例2)錠剤 (Formulation example 2) Tablet
上記成分及び分量をとり、日局製剤総則「錠剤」の項に準じて錠剤を製造する。なお、所望により剤皮を塗布する。 Taking the above ingredients and amounts, tablets are produced according to the section “General Tablet Preparation Guidelines”. If desired, a coating is applied.
(試験例)抗潰瘍効果試験
(1)被検物質
インドメタシンはSigma-Aldrich製のものを、トラネキサム酸及び有胞子性乳酸菌は第一三共プロファーマ製のものを使用した。
被験物質はメチルセルロース(和光純薬工業製)を注射用水(大塚製薬製)に溶解した0.5%メチルセルロース溶液中に懸濁させて調製した。
(Test example) Anti-ulcer effect test (1) Test substance Indomethacin was manufactured by Sigma-Aldrich, and tranexamic acid and spore-forming lactic acid bacteria were manufactured by Daiichi Sankyo Propharma.
The test substance was prepared by suspending methylcellulose (manufactured by Wako Pure Chemical Industries) in a 0.5% methylcellulose solution dissolved in water for injection (manufactured by Otsuka Pharmaceutical).
(2)使用動物
Crl:CD雄性ラット5週齢(日本チャールスリバー)を使用した。動物は温度21−27℃、湿度35−75%、照明時間7−19時に制御されたラット飼育室内で個別飼育した。固形試料(オリエンタル酵母工業ラット用固形飼料、CRF-1)及び水道水を自由に摂取させ、1週間予備飼育した後、毛並、体重増加などの一般症状の良好な動物を選別して供試した。
(2) Animals used Crl: CD male rats 5 weeks old (Nippon Charles River) were used. The animals were individually housed in a rat breeding room controlled at a temperature of 21-27 ° C., a humidity of 35-75%, and an illumination time of 7-19. A solid sample (oriental yeast industrial rat chow, CRF-1) and tap water were freely ingested and pre-bred for 1 week, after which animals with good general symptoms such as fur and weight gain were selected and tested. .
(3)試験方法
24時間以上絶食したラットに、フレキシブル胃管を装着したディスポーザブルシリンジを用いて、被験物質を経口投与した。なお、被験物質はスターラーを用いて撹拌しながら使用した。
被験薬投与後5時間後に、頚椎脱臼により動物を安楽死させ、速やかに胃を摘出し、内部に生理食塩液を10mL 充填後、2%ホルマリンに浸して翌日まで固定した。固定した胃を大弯に沿って切開し、デジタルノギスを用いて胃粘膜における傷害の長さを測定した。なお、個体の胃粘膜における傷害の長さは、長径を計測し、総和を算出した。
(3) Test method A test substance was orally administered to a rat fasted for 24 hours or more using a disposable syringe equipped with a flexible gastric tube. The test substance was used with stirring using a stirrer.
Five hours after administration of the test drug, the animals were euthanized by cervical dislocation, the stomach was quickly removed, 10 mL of physiological saline was filled therein, and then immersed in 2% formalin and fixed until the next day. The fixed stomach was incised along the large vagina and the length of injury in the gastric mucosa was measured using a digital caliper. The length of the injury in the gastric mucosa of the individual was calculated by measuring the major axis and calculating the sum.
(4)試験結果
NSAIDs(インドメタシン)の投与による、胃粘膜における傷害の長さの総和(潰瘍長、mm)の結果を表3に示す。表3には、NSAIDsにトラネキサム酸、又は有胞子乳酸菌を各々投与した場合、及び、NSAIDsにトラネキサム酸と有胞子乳酸菌を同時に投与した場合の結果を示した。なお、いずれの投与群も1群9匹であり、潰瘍長(mm)はその平均値で示した。
(4) Test results Table 3 shows the results of the total length of injury (ulcer length, mm) in the gastric mucosa by administration of NSAIDs (indomethacin). Table 3 shows the results when tranexamic acid or spore lactic acid bacteria were respectively administered to NSAIDs, and when tranexamic acid and spore lactic acid bacteria were simultaneously administered to NSAIDs. Each administration group had 9 mice per group, and the ulcer length (mm) was shown as an average value.
表3に示したように、インドメタシンにトラネキサム酸を併用しても、インドメタシンによる胃粘膜傷害の軽減作用はほとんどみられなかった。また、インドメタシンに有胞子性乳酸菌を併用した場合には、インドメタシンによる胃粘膜傷害を増悪させる結果であった。 As shown in Table 3, even when tranexamic acid was used in combination with indomethacin, the effect of reducing gastric mucosal damage by indomethacin was hardly observed. Further, when indomethacin was used in combination with spore-forming lactic acid bacteria, the gastric mucosal damage caused by indomethacin was exacerbated.
一方、インドメタシンにトラネキサム酸及び有胞子性乳酸菌を同時併用すると、胃粘膜傷害の長さが顕著に短くなることが判明した。 On the other hand, it was found that when tranexamic acid and spore-forming lactic acid bacteria were used in combination with indomethacin, the length of gastric mucosal injury was significantly shortened.
以上の結果から、トラネキサム酸と有胞子性乳酸菌を含有する医薬組成物は、NSAIDsによる胃粘膜障害を著しく軽減し、潰瘍を抑制することがわかった。 From the above results, it was found that the pharmaceutical composition containing tranexamic acid and spore-forming lactic acid bacteria significantly reduced gastric mucosal damage caused by NSAIDs and suppressed ulcers.
本発明の医薬組成物は、NSAIDsによる潰瘍を抑制するので、抗潰瘍剤として利用できる。 Since the pharmaceutical composition of the present invention suppresses ulcers caused by NSAIDs, it can be used as an anti-ulcer agent.
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