JPWO2006129479A1 - Gastrointestinal composition - Google Patents
Gastrointestinal composition Download PDFInfo
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- JPWO2006129479A1 JPWO2006129479A1 JP2007518901A JP2007518901A JPWO2006129479A1 JP WO2006129479 A1 JPWO2006129479 A1 JP WO2006129479A1 JP 2007518901 A JP2007518901 A JP 2007518901A JP 2007518901 A JP2007518901 A JP 2007518901A JP WO2006129479 A1 JPWO2006129479 A1 JP WO2006129479A1
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- 230000002496 gastric effect Effects 0.000 title claims abstract description 26
- 239000000203 mixture Substances 0.000 title claims abstract description 23
- MYGVPKMVGSXPCQ-JEDNCBNOSA-N Methylmethionine sulfonium salt Chemical compound [Cl-].C[S+](C)CC[C@H](N)C(O)=O MYGVPKMVGSXPCQ-JEDNCBNOSA-N 0.000 claims abstract description 31
- 206010036790 Productive cough Diseases 0.000 claims abstract description 16
- 208000024794 sputum Diseases 0.000 claims abstract description 16
- 210000003802 sputum Anatomy 0.000 claims abstract description 16
- 206010000060 Abdominal distension Diseases 0.000 claims abstract description 10
- 206010047700 Vomiting Diseases 0.000 claims abstract description 10
- 201000006549 dyspepsia Diseases 0.000 claims abstract description 10
- 230000004596 appetite loss Effects 0.000 claims abstract description 9
- 208000019017 loss of appetite Diseases 0.000 claims abstract description 9
- 235000021266 loss of appetite Nutrition 0.000 claims abstract description 9
- 210000002784 stomach Anatomy 0.000 claims abstract description 9
- 230000008673 vomiting Effects 0.000 claims abstract description 9
- 206010028813 Nausea Diseases 0.000 claims abstract description 8
- 230000008693 nausea Effects 0.000 claims abstract description 8
- 206010015137 Eructation Diseases 0.000 claims abstract description 7
- 208000027687 belching Diseases 0.000 claims abstract description 5
- 210000001035 gastrointestinal tract Anatomy 0.000 claims description 10
- 206010020710 Hyperphagia Diseases 0.000 claims description 3
- 230000003213 activating effect Effects 0.000 claims description 2
- 230000029087 digestion Effects 0.000 claims description 2
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- 235000019512 sardine Nutrition 0.000 description 1
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Classifications
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- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
- A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
- A61K31/198—Alpha-amino acids, e.g. alanine or edetic acid [EDTA]
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/28—Asteraceae or Compositae (Aster or Sunflower family), e.g. chamomile, feverfew, yarrow or echinacea
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- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
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- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/28—Asteraceae or Compositae (Aster or Sunflower family), e.g. chamomile, feverfew, yarrow or echinacea
- A61K36/284—Atractylodes
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- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/08—Drugs for disorders of the alimentary tract or the digestive system for nausea, cinetosis or vertigo; Antiemetics
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- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
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- A—HUMAN NECESSITIES
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- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
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- A—HUMAN NECESSITIES
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Abstract
本発明は、胃腸薬としての効果が著しく増強された胃腸薬を提供する。メチルメチオニンスルホニウムクロライドおよび蒼朮を含む胃腸薬組成物、特に、げっぷ、はきけ、悪心もしくは嘔吐の抑制、又は胸つかえ、もたれ、消化不良、胃部・腹部膨満感もしくは食欲不振の解消のための胃腸薬組成物。The present invention provides a gastrointestinal drug with significantly enhanced effects as a gastrointestinal drug. Gastrointestinal composition comprising methylmethioninesulfonium chloride and sputum, especially gastrointestinal for the suppression of belching, scalding, nausea or vomiting, or chest gripping, leaning, indigestion, stomach / abdominal fullness or loss of appetite Drug composition.
Description
本発明は、メチルメチオニンスルホニウムクロライド（ＭＭＳＣ）及び蒼朮を含む、効力が顕著に増強された胃腸薬組成物に関する。 The present invention relates to a gastrointestinal composition with significantly enhanced efficacy comprising methylmethionine sulfonium chloride (MMSC) and sputum.
一般に胃腸薬とは、食べ過ぎ、胸やけ、もたれ、胃痛、吐き気、嘔吐などの症状を緩和する作用を示し、胃腸を健康な状態に維持するあるいは健康な状態に回復するために広く用いられている医薬であり、消化薬、健胃薬、制酸薬、複合胃腸薬、胃腸鎮痛鎮痙薬などに細分類される。 Gastrointestinal drugs are generally used to relieve symptoms such as overeating, heartburn, leaning, stomach pain, nausea and vomiting, and are widely used to maintain or restore the gastrointestinal tract to a healthy state. This medicine is subdivided into digestive drugs, stomachic medicines, antacids, compound gastrointestinal drugs, gastrointestinal analgesics and antispasmodics.
メチルメチオニンスルホニウムクロライド（ＭＭＳＣ）は、荒れた胃粘膜を修復する作用を有することから、胃腸薬、特に複合胃腸薬の一成分として広く利用されている。また、蒼朮（ソウジュツ）は、ホソバオケラ（Atractylodes lancea De Candolle）またはAtractylodes chinensis Koidzumiの根茎であり、古来生薬として認知され、主に健胃消化薬や止瀉整腸薬などとして利用されてきている（非特許文献１）。しかしながら、両者を配合した医薬組成物、特に胃腸薬は、これまでのところ、存在していない。 Methyl methionine sulfonium chloride (MMSC) is widely used as a component of gastrointestinal drugs, particularly complex gastrointestinal drugs, because it has an action of repairing rough gastric mucosa. In addition, sardine is a rhizome of Atractylodes lancea De Candolle or Atractylodes chinensis Koidzumi, and is recognized as an ancient herbal medicine, and has been mainly used as a gastrointestinal digestive and anti-enteric agent ( Non-patent document 1). However, so far, there is no pharmaceutical composition containing both, particularly a gastrointestinal drug.
本発明の目的は、従来の胃腸薬に比べて有効性が顕著に高められた新たな胃腸薬組成物を提供するものである。 An object of the present invention is to provide a new gastrointestinal drug composition with significantly improved effectiveness compared to conventional gastrointestinal drugs.
本発明者らは、胃粘膜修復剤として知られるメチルメチオニンスルホニウムクロライド（ＭＭＳＣ）と、健胃消化薬あるいは止瀉整腸薬として知られている蒼朮とを組み合わせて使用すると、顕著な消化管の運動賦活化作用を示し、その結果、げっぷ、はきけ、悪心もしくは嘔吐の抑制、又は胸つかえ、もたれ、消化不良、胃部・腹部膨満感もしくは食欲不振の解消などの胃腸薬としての効果が飛躍的に高まることを見いだし、本発明を完成した。 When the present inventors use a combination of methylmethionine sulfonium chloride (MMSC), which is known as a gastric mucosal repair agent, and sputum, which is known as a healthy gastrointestinal or antistatic antienteric agent, Exhibits exercise stimulating effects, and as a result, the effects of gastrointestinal drugs such as suppression of burping, scalding, nausea or vomiting, or chest hold, leaning, indigestion, stomach / abdominal fullness or loss of appetite As a result, the present invention has been completed.
すなわち、本発明は、ＭＭＳＣ及び蒼朮を含む胃腸薬組成物を提供する。また本発明は、げっぷ、はきけ、悪心もしくは嘔吐の抑制、又は胸つかえ、もたれ、消化不良、胃部・腹部膨満感もしくは食欲不振の解消のためのＭＭＳＣ及び蒼朮を含む胃腸薬組成物に関する。 That is, the present invention provides a gastrointestinal composition comprising MMSC and sputum. The present invention also relates to a gastrointestinal composition comprising MMSC and sputum for suppressing belching, scalding, nausea or vomiting, or chest relief, leaning, indigestion, gastric / abdominal bloating or loss of appetite.
本発明である胃腸薬組成物は、ＭＭＳＣあるいは蒼朮をそれぞれ単独で使用しても得ることのできない相乗的に高められた消化管の運動賦活化作用によって、ＭＭＳＣが有しているげっぷ、はきけ、悪心もしくは嘔吐の抑制、又は胸つかえ、もたれ、消化不良、胃部・腹部膨満感もしくは食欲不振の解消などの効果が顕著に高められるという効果を奏する。 The gastrointestinal composition according to the present invention has a synergistically enhanced gastrointestinal motility activation action that cannot be obtained by using MMSC or sputum alone, respectively, so that MMSC has a burp, The effects of suppressing nausea or vomiting, or holding the chest, leaning, indigestion, feeling of fullness of stomach / abdomen or loss of appetite are remarkably enhanced.
ＭＭＳＣは、１９５９年に販売が開始された医薬であり、主に胃粘膜修復剤として、あるいは慢性肝疾患における肝機能の改善のために用いられてきた。しかし、ＭＭＳＣと蒼朮が併用して使用されることによって顕著な消化管の運動賦活化作用を示し、その結果、げっぷ、はきけ、悪心もしくは嘔吐の抑制効果、又は胸つかえ、もたれ、消化不良、胃部・腹部膨満感もしくは食欲不振の解消効果が、ＭＭＳＣを単独で使用した場合に比べて顕著に高められることについては、これまでのところ報告も示唆もない。 MMSC is a medicine that was launched in 1959 and has been used mainly as a gastric mucosal repair agent or for improving liver function in chronic liver disease. However, when used in combination with MMSC and sputum, it shows a significant gastrointestinal motility activation effect, and as a result, suppresses belching, scalding, nausea or vomiting, or chest hold, leaning, indigestion, To date, there has been no report or suggestion that the effect of relieving stomach / abdominal bloating or loss of appetite can be significantly enhanced compared to using MMSC alone.
また、蒼朮に関しても、消化管の運動を亢進する機能は知られていた（非特許文献１）ものの、ＭＭＳＣとの併用によってかかる機能が相乗的に増強され、その結果、ＭＭＳＣと蒼朮を含む胃腸薬組成物としての効果が相乗的に高められることについては、これまでのところ報告も示唆もない。 As for sputum, the function of enhancing the movement of the gastrointestinal tract has been known (Non-patent Document 1), but the function is synergistically enhanced by the combined use with MMSC, and as a result, the gastrointestinal tract including MMSC and sputum There has been no report or suggestion so far about synergistic enhancement of the effect as a pharmaceutical composition.
本発明は、従来組み合わされて使用されることのなかったＭＭＳＣと蒼朮との併用によって、それぞれ単独の使用では達成されない相乗的に高められた効果を有する胃腸薬組成物を提供するものである。 The present invention provides a gastrointestinal composition that has a synergistically enhanced effect that cannot be achieved by using MMSC and sputum, which have not been used in combination in the past, each of which is not achieved by use alone.
本発明の胃腸薬組成物は、後述する実施例において示されるように、腸管輸送率で表される消化管の運動を賦活化させる作用を有している。その効果は、ＭＭＳＣ、蒼朮それぞれ単独で使用したときに認められる効果の合算よりも有意に高く、相乗的に作用して消化管の運動を賦活化していることが認められる。 The gastrointestinal composition of the present invention has an action of activating the movement of the digestive tract represented by the intestinal tract transport rate, as shown in Examples described later. The effect is significantly higher than the sum of the effects observed when MMSC and cocoon are used alone, and it is recognized that they act synergistically to activate gastrointestinal motility.
以下の推論に拘束されるものではないが、本発明においては、かかる消化管運動の相乗的な賦活化によって、腸管内容物の滞留を原因とするげっぷ、はきけ、嘔吐、胸つかえ、もたれ、消化不良、胃部・腹部膨満感ならびに食欲不振などの症状、特に飲み過ぎもしくは食べ過ぎによって生じるこれらの症状が、ＭＭＳＣあるいは蒼朮を単独で使用する場合に比べて、顕著に改善されているものと推察される。また、消化管運動の相乗的な賦活化によって、腸管内容物の滞留が解消され、消化促進をより強く促すこともできる。 Although not bound by the following reasoning, in the present invention, by synergistic activation of such gastrointestinal motility, burping, scalding, vomiting, chest gripping, leaning due to retention of intestinal contents, Symptoms such as indigestion, stomach and abdominal bloating, and loss of appetite, especially those caused by excessive drinking or eating, are markedly improved compared to using MMSC or sputum alone. Inferred. In addition, the synergistic activation of gastrointestinal motility eliminates the retention of intestinal contents and can promote the promotion of digestion more strongly.
本発明で使用するＭＭＳＣは、例えば米沢浜理薬品工業（株）から市販されているものを利用してもよく、また特公昭３６−１３２０９号公報に記載された方法に従って合成し、使用してもよい。また、蒼朮についても、生薬成分として広く流通し使用されているものを入手し、使用すればよい。 The MMSC used in the present invention may be, for example, those commercially available from Yonezawa Hamari Pharmaceutical Co., Ltd., or synthesized and used according to the method described in Japanese Patent Publication No. 36-13209. Also good. As for koji, what is widely distributed and used as a crude drug component may be obtained and used.
ＭＭＳＣと蒼朮の配合比とこれらの相乗作用については、重量比でＭＭＳＣ：蒼朮（原生薬換算）が９部：８部〜３部：５００部、特に１部：２部〜１部：５部である場合において、併用による相乗的な効果を特に強く発揮させることができる。またＭＭＳＣと蒼朮の組成物中の配合量は、それぞれ胃腸薬組成物として配合可能な量の範囲から、前期の配合比を満足させる量をそれぞれ決定して使用すればよい。 As for the blending ratio of MMSC and koji and their synergistic effect, the weight ratio of MMSC: koji (in terms of drug substance) is 9 parts: 8 parts to 3 parts: 500 parts, particularly 1 part: 2 parts to 1 part: 5 parts. In this case, the synergistic effect of the combined use can be exerted particularly strongly. Further, the blending amounts in the MMSC and sputum compositions may be determined and used in amounts that satisfy the blending ratio of the previous period from the range of amounts that can be blended as the gastrointestinal composition.
また、本発明の胃腸薬組成物は、ＭＭＳＣと蒼朮の他に、医薬上許容される担体や他の医薬成分、賦形剤、結合剤、崩壊剤、滑沢剤、着色剤、矯味剤等を含む医薬組成物の形態としても使用することができる。 In addition to MMSC and sputum, the gastrointestinal composition of the present invention includes pharmaceutically acceptable carriers and other pharmaceutical ingredients, excipients, binders, disintegrants, lubricants, coloring agents, flavoring agents, etc. Can also be used in the form of a pharmaceutical composition comprising
賦形剤としては、乳糖、デンプン類、結晶セルロース、蔗糖、マンニトール、軽質無水ケイ酸等が挙げられる。結合剤としては、ヒドロキシプロピルメチルセルロース、ヒドロキシプロピルセルロース、ゼラチン、アルファー化デンプン、ポリビニルピロリドン、ポリビニルアルコール、プルラン等が挙げられる。崩壊剤としては、カルメロース、カルメロースカルシウム、クロスカルメロースナトリウム、クロスポビドン、トウモロコシ澱粉、低置換度ヒドロキシプロピルセルロース等が挙げられる。滑沢剤としては、ステアリン酸マグネシウム、タルク等が挙げられる。着色剤としては、タール色素、三二酸化鉄等が挙げられる。矯味剤としてはステビア、アスパルテーム、香料等が挙げられる。 Examples of the excipient include lactose, starches, crystalline cellulose, sucrose, mannitol, light anhydrous silicic acid and the like. Examples of the binder include hydroxypropylmethylcellulose, hydroxypropylcellulose, gelatin, pregelatinized starch, polyvinylpyrrolidone, polyvinyl alcohol, pullulan and the like. Examples of the disintegrant include carmellose, carmellose calcium, croscarmellose sodium, crospovidone, corn starch, and low-substituted hydroxypropylcellulose. Examples of the lubricant include magnesium stearate and talc. Examples of the colorant include tar pigments and iron sesquioxide. Examples of the corrigent include stevia, aspartame, and fragrances.
本発明の胃腸薬組成物は、目的に応じて散剤、顆粒剤、錠剤、チュアブル錠、フィルムコーティング錠、糖衣錠、ドリンク剤、軟カプセル剤、硬カプセル剤、ゼリー剤等の剤型に製造して使用することができる。特に、散剤、顆粒剤、錠剤、フィルムコーティング錠の剤型に製造して使用することが好ましい。 The gastrointestinal composition of the present invention is produced in dosage forms such as powders, granules, tablets, chewable tablets, film-coated tablets, sugar-coated tablets, drinks, soft capsules, hard capsules, jelly agents, etc. according to the purpose. Can be used. In particular, it is preferable to manufacture and use in the dosage form of a powder, a granule, a tablet, and a film coating tablet.
また、ＭＭＳＣ及び蒼朮を含む胃腸薬組成物のヒトに対する投与量としては、剤型、疾患の程度、患者の年齢等の要素に依存するが、通常成人に対してＭＭＳＣを基本として３０〜３０００ｍｇ／日程度、特に１００〜２２５ｍｇ／日程度を投与すればよく、かかる投与量にあわせて、蒼朮の投与量を決定することができる。 The dose of a gastrointestinal composition containing MMSC and sputum to humans depends on factors such as the dosage form, the degree of disease, the age of the patient, etc., but usually 30 to 3000 mg / day based on MMSC for adults. About a day, particularly about 100 to 225 mg / day may be administered, and the dose of sputum can be determined according to such a dose.
以下に、実施例を用いて本発明を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 in detail with reference to examples, but the present invention is not limited thereto.
試験前日に絶食した５週齢のｄｄＹ系雄性マウスに、０．５％メチルセルロース（以下ＭＣという）に懸濁したメチルメチオニンスルホニウムクロライド（１０００ｍｇ／ｋｇ、以下Ｍという）、ソウジュツ乾燥エキスＳ（３００ｍｇ／ｋｇ、原生薬換算量として３０００ｍｇ／ｋｇ。以下Ｓという。）及びそれらの混合物（以下Ｍ＋Ｓという）を経口投与し、その15分後に活性炭素末懸濁液を経口投与した。さらにその30分後に動物を頚椎脱臼にてと殺し、幽門部から回盲部までの腸管を摘出した。被験物質の腸管輸送能は、幽門部からの炭素末の移動距離を腸管の全長で除し、腸管輸送率として表した。 Five-week-old ddY male mice fasted on the day before the test were treated with methylmethionine sulfonium chloride (1000 mg / kg, hereinafter referred to as M) suspended in 0.5% methylcellulose (hereinafter referred to as MC), dried dried extract S (300 mg / day). kg, 3000 mg / kg as the amount of drug substance (hereinafter referred to as S) and a mixture thereof (hereinafter referred to as M + S) were orally administered, and 15 minutes later, the activated carbon powder suspension was orally administered. Further 30 minutes later, the animals were killed by cervical dislocation, and the intestinal tract from the pylorus to the ileocecal region was removed. The intestinal transport ability of the test substance was expressed as the intestinal transport rate by dividing the movement distance of the carbon powder from the pylorus by the total length of the intestinal tract.
試験結果を表１に示す。
腸管輸送率は、ＭＣを投与したコントロール群で48.5%、Ｍ群で69.0%、Ｓ群で53.0%、Ｍ＋Ｓ群で76.2%であった。コントロール群の腸管輸送率を１とした時のＭ＋Ｓ群の腸管輸送率の割合は1.57であり、単味群の積の1.55（1.42×1.09）に比べて大きく、相乗効果ありと判定された。このことから、本発明が消化管運動機能を促進し、その結果、げっぷ、はきけ、悪心もしくは嘔吐の抑制、又は胸つかえ、もたれ、消化不良、胃部・腹部膨満感もしくは食欲不振の解消などにおいて顕著に増強された胃腸薬組成物として非常に有用であることが明らかとなった。 The intestinal transport rate was 48.5% in the control group administered with MC, 69.0% in the M group, 53.0% in the S group, and 76.2% in the M + S group. The ratio of the intestinal tract transport rate of the M + S group when the intestinal tract transport rate of the control group was 1, was 1.57, which was larger than the simple group product of 1.55 (1.42 × 1.09), and was judged to have a synergistic effect. From this, the present invention promotes the gastrointestinal motility function, and as a result, suppresses belching, scalding, nausea or vomiting, or chest gripping, leaning, indigestion, stomach / abdominal bloating or loss of appetite, etc. Was found to be very useful as a gastrointestinal composition that was significantly enhanced.
賦形剤として乳糖を用い、常法の湿式造粒法によってＭＭＳＣを含む顆粒を造粒した後、常法により圧縮成形して１錠当たり２５ｍｇのＭＭＳＣを含む錠剤Aを製造した。また、同様にして１錠当たり２５ｍｇのＭＭＳＣならびに １２ｍｇ（原生薬換算）の蒼朮を含む錠剤Ｂを製造した。 Granules containing MMSC were granulated by a conventional wet granulation method using lactose as an excipient, and then compression-molded by a conventional method to produce tablet A containing 25 mg of MMSC per tablet. Similarly, Tablet B containing 25 mg of MMSC and 12 mg (in terms of active ingredient) per tablet was produced.
胃について一定の腹部不定愁訴を訴える２０〜５０代のボランティア男性１０名を無作為に選抜し、５名づつの２群（Ａ群ならびにＢ群）に分けた。Ａ群に対しては錠剤Ａを、Ｂ群には錠剤Ｂを、それぞれ３日間連続して毎食後２錠づつ服用したときの、服用前・中・後における不定愁訴の症状の推移をアンケート形式で回答してもらった。この結果を表２に示す。
表２から明らかなように、本発明の胃腸薬組成物を服用したＢ群において、腹部不定愁訴の症状の顕著な改善効果が確認された。
As is apparent from Table 2, in group B taking the gastrointestinal composition of the present invention, a remarkable improvement effect on the symptoms of abdominal indefinite complaints was confirmed.
Claims (5)
The gastrointestinal composition according to claim 1 for activating the motor function of the digestive tract.
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| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
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| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |