KR20080003318A - Gastrointestinal motor activation regulator - Google Patents
Gastrointestinal motor activation regulator Download PDFInfo
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- KR20080003318A KR20080003318A KR1020077021585A KR20077021585A KR20080003318A KR 20080003318 A KR20080003318 A KR 20080003318A KR 1020077021585 A KR1020077021585 A KR 1020077021585A KR 20077021585 A KR20077021585 A KR 20077021585A KR 20080003318 A KR20080003318 A KR 20080003318A
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- nausea
- gastrointestinal motility
- regulator
- motor activation
- revitalization
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- 230000004913 activation Effects 0.000 title abstract description 4
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- 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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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/14—Prodigestives, e.g. acids, enzymes, appetite stimulants, antidyspeptics, tonics, antiflatulents
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Abstract
Description
본 발명은 메틸메티오닌설포늄클로라이드(MMSC)의 새로운 약효에 의거하는 소화관 운동 부활 조정제에 관한 것이다.The present invention relates to a gastrointestinal kinetic activation modulator based on the novel efficacy of methylmethioninesulfonium chloride (MMSC).
최근, 소화관 운동 기능의 저하는 만성 위염, 역류성 식도염, 복부 부정수소 혹은 가성 장폐색 등의 여러 가지의 위장장해를 가져오는 질병의 일종으로 이해, 인식되게 되었다. 그 때문에 소화관의 운동 기능을 활력화시킬 수 있는 약물을 포함하는 의약은 상기 만성 위염 등의 위장장해를 해소 혹은 완화시킬 수 있는 의약, 즉 소화관 운동 부활 조정제로서 이용 가능하다고 인식되게 되었다.Recently, a decrease in the functioning of the gastrointestinal motility has been understood and recognized as a kind of disease causing various gastrointestinal disorders such as chronic gastritis, reflux esophagitis, abdominal hydrogen or pseudointestinal obstruction. For this reason, it is recognized that a medicine containing a drug capable of activating the exercise function of the digestive tract can be used as a medicine that can relieve or alleviate the gastrointestinal disorders such as chronic gastritis, that is, as a regulator for reactivating the digestive tract.
이 소화관 운동 부활 조정제의 예로서는, 시사프라이드(비특허문헌 1, 2)와 메토클로프라마이드(비특허문헌 3, 4) 등이 알려져 있다. 또한 생약성분의 일종인 창출(蒼朮)에도 이 소화관 운동 부활 조정효과가 있는 것이 알려져 있다(비특허문헌 5).Cisaprides (non-patent documents 1, 2), metoclopramide (non-patent documents 3, 4), and the like are known as examples of this digestive tract exercise revitalization regulator. In addition, it is known that the production of herbal medicines has an effect of adjusting the digestive tract reactivation effect (Non Patent Literature 5).
그러나, 메토클로프라마이드에는 항-도파민 작용에 의한 추체외로 증상이, 시사프라이드에는 파킨슨 증상이 각각 부작용으로서 보고되고 있으며, 그 밖에도, 심실성 부정맥이나 과민증 등의 부작용도 확인되고 있다. 또 창출은 생약성분으로서 온화한 효력을 나타내지만, 반면에, 약리작용이 충분하다고는 말하기 어렵다.However, metoclopramide has been reported as an extrapyramidal symptom due to anti-dopamine action and Parkinson's symptom as a cisapride, respectively, and side effects such as ventricular arrhythmias and hypersensitivity have also been confirmed. In addition, creation has a mild effect as an herbal ingredient, on the other hand, it is difficult to say that the pharmacological action is sufficient.
[비특허문헌1] Schuurkes,J.A.J.,et al., 1985년, J. Pharmacol. Exp. Ther., 제234권, 제775쪽.[Non-Patent Document 1] Schuurkes, J. A. J., et al., 1985, J. Pharmacol. Exp. Ther., Vol. 234, p. 775.
[비특허문헌2] Schuurkes,J.A.J.,et al., 1984년, Gastrointestinal Motility, Roman, C., 제95쪽, MTP 프레스, Lancaster.[Non-Patent Document 2] Schuurkes, J.A.J., et al., 1984, Gastrointestinal Motility, Roman, C., page 95, MTP press, Lancaster.
[비특허문헌3] 후쿠하라 타케시 외: 일평활근지, 1966년, 제2권, 제1호, 제15쪽, [PP11038][Non-Patent Document 3] Takeshi, Fukuhara et al .: One Smooth Muscle, 1966, Vol. 2, No. 1, page 15, [PP11038]
[비특허문헌4] 쿠마다 시게아츠시 외: 약학연구, 1968년, 제39권, 제2호, 제44쪽, [PP11550][Non-Patent Document 4] Shigeatsu City, Kumada et al .: Pharmaceutical Research, 1968, Vol. 39, No. 2, page 44, [PP11550]
[비특허문헌5] 제14개정 일본약전해설서, 2001년, D-674∼677쪽[Non-Patent Document 5] The 14th Revision of the Japanese Pharmacopoeia, 2001, pp. D-674-677
발명이 해결하고자 하는 과제Problems to be Solved by the Invention
본 발명의 목적은 소화관 운동 부활 조정작용을 가지는 새로운 의약을 제공하는 것에 있다.Disclosure of Invention An object of the present invention is to provide a new medicament having a coordination effect on digestive tract movement.
과제를 해결하기 위한 수단Means to solve the problem
본 발명자들은 의외로 위점막 수복제로 알려진 메틸메티오닌설포늄클로라이드(MMSC)가 소화관 운동 부활 조정작용을 가지고 있는 것을 발견하고, 본 발명을 완성하였다.The inventors have discovered that methylmethioninesulfonium chloride (MMSC), which is surprisingly known as gastric mucosal repair agent, has a function of regulating digestive tract motility and completed the present invention.
즉, 본 발명은 MMSC를 포함하는 소화관 운동 부활 조정제에 관한 것이다. 또 본 발명은 트림, 구역질, 오심 혹은 구토의 억제, 또는 조기 포만감, 체증, 소화불량, 위부ㆍ복부 팽만감 혹은 식욕부진의 해소를 위한, MMSC을 함유하는 소화관 운동 부활 조정제도 제공한다.That is, the present invention relates to a gastrointestinal motility revitalization regulator comprising MMSC. The present invention also provides a gastrointestinal motility modulator containing MMSC for suppressing burping, nausea, nausea or vomiting, or for relieving premature satiety, congestion, indigestion, stomach and abdominal bloating or loss of appetite.
발명의 효과Effects of the Invention
본 발명의 소화관 운동 부활 조정제는 생약성분인 창출에 비해서 약리작용이 강하여 유효성이 우수하다. 한편, MMSC에는 항-도파민 작용이나 시사프라이드나 메토클로프라마이드에 인정되는 추체외로 증상이나 파킨슨 증상 등의 중추신경계의 부작용, 다른 부작용 등은 보고되지 않고 있다. 따라서 MMSC를 함유하는 의약은 높은 약리작용과 안전성을 구비한 소화관 운동 부활 조정제로서 이용할 수 있다.Digestive tract exercise reactivation regulator of the present invention has a strong pharmacological action compared to the creation of the herbal ingredient is excellent in effectiveness. On the other hand, MMSCs do not report anti-dopamine action, extrapyramidal symptoms or other side effects of central nervous system such as Parkinson's symptoms recognized by cisapride or metoclopramide. Therefore, a medicament containing MMSC can be used as a modulator of digestive tract exercise revitalization with high pharmacological action and safety.
발명을 실시하기 위한 최선의 형태Best Mode for Carrying Out the Invention
MMSC는 1959년에 판매가 시작된 의약으로, 주로 위점막 수복제로서, 혹은 만성 간질병에 있어서의 간기능의 개선을 위해서 사용되어 왔지만, MMSC가 소화관 운동 부활 조정 작용을 가지며, 따라서 소화관 운동 부활 조정제가 될 수 있는 것에 대해서는, 지금까지는 보고된 바나 시사된 바도 없었다. 본 발명은 이 MMSC의 새로운 용도를 제공하는 것이다.MMSC is a drug that was launched in 1959 and has been used primarily as a gastric mucosal repair or to improve liver function in chronic epilepsy, but MMSC has a role in regulating gastrointestinal motility. As far as possible, nothing has been reported or suggested. The present invention provides a new use of this MMSC.
본 발명에서 사용하는 MMSC는, 예를 들면 요네자와하마리약품공업(주)에서 시판되고 있는 것을 사용하여도 좋고, 또 일본 특허공보 S36-13209호에 기재된 방법에 따라서 합성하여 사용하여도 좋다.MMSC used by this invention may use what is marketed by Yonezawa Hamari Pharmaceutical Co., Ltd., for example, and may synthesize | combine and use it according to the method of Unexamined-Japanese-Patent No. S36-13209.
또한, 본 발명의 소화관 운동 부활 조정제는 MMSC의 단신의 형태, 또는 의약상 허용되는 담체나 다른 의약성분, 부형제, 결합제, 붕해제, 활택제, 착색제, 교미제 등을 포함하는 의약조성물의 형태로서도 사용할 수 있다.In addition, the gastrointestinal motility modulator of the present invention is also in the form of a short form of MMSC or a pharmaceutical composition containing a pharmaceutically acceptable carrier or other pharmaceutical ingredients, excipients, binders, disintegrants, lubricants, colorants, copulation agents, etc. Can be used.
부형제로서는 락토스, 전분류, 결정 셀룰로오스, 슈크로스, 만니톨, 경질 무수규산 등을 들 수 있다. 결합제로서는 하이드록시프로필메틸셀룰로오스, 하이드록시프로필셀룰로오스, 젤라틴, 알파화 전분, 폴리비닐피롤리돈, 폴리비닐알코올, 풀루란 등을 들 수 있다. 붕해제로서는 카멜로오스, 카멜로오스칼슘, 크로스카멜로오스나트륨, 크로스포비돈, 옥수수 전분, 저치환도 하이드록시프로필셀룰로오스 등을 들 수 있다. 활택제로서는 스테아르산마그네슘, 탈크 등을 들 수 있다. 착색제로서는 타르 색소, 삼이산화철 등을 들 수 있다. 교미제로서는 스테비어, 아스파르탐, 향료 등을 들 수 있다.Examples of the excipient include lactose, starch, crystalline cellulose, sucrose, mannitol, hard silicic anhydride, and the like. Examples of the binder include hydroxypropyl methyl cellulose, hydroxypropyl cellulose, gelatin, alpha starch, polyvinylpyrrolidone, polyvinyl alcohol, pullulan and the like. Examples of the disintegrant include cameloose, cameloose calcium, croscarmellose sodium, crospovidone, corn starch, low-substituted hydroxypropyl cellulose and the like. Examples of the lubricants include magnesium stearate and talc. As a coloring agent, a tar pigment | dye, iron trioxide, etc. are mentioned. Examples of the mating agent include stevia, aspartame, fragrance, and the like.
본 발명의 소화관 운동 부활 조정제는 목적에 따라서 분말제, 과립제, 정제, 츄어블정, 필름 코팅정, 당의정, 드링크제, 연캡슐제, 경캡슐제, 젤리제 등의 제형으로 제조하여 사용할 수 있다. 특히, 분말제, 과립제, 정제, 필름 코팅정의 제형으로 제조하여 사용하는 것이 바람직하다.Digestive tract exercise revitalization regulator of the present invention can be prepared and used in the form of powders, granules, tablets, chewable tablets, film coated tablets, dragees, drinks, soft capsules, hard capsules, jellys and the like according to the purpose. In particular, it is preferable to prepare and use in the form of powder, granules, tablets, film-coated tablets.
MMSC를 소화관 운동 부활 조정제로서 사용하는 경우의 투여량은 제형, 질병의 정도, 환자의 연령 등의 요소에 의존하지만, 보통 성인에 대해서 MMSC를 30∼3000㎎/일 정도, 특히 150∼225㎎/일 정도를 투여하는 것이 바람직하다.Dosage when using MMSCs as a modulator of gastrointestinal motility depends on factors such as dosage form, disease severity, age of the patient, etc., but usually about 30-3000 mg / day, especially 150-225 mg / day, for adults. It is preferable to administer about a day.
본 발명의 소화관 운동 부활 조정제는 후술하는 실시예에서 나타내듯이, 장관 수송율을 향상시키는 작용을 가지고 있다. 따라서 본 발명의 소화관 운동 부활 조정제는 장관 내용물의 체류에 기인하는 만성 위염, 역류성 식도염, 복부 부정수소 혹은 가성 장폐색 등의 여러 가지의 증상을 해소할 수 있다. 또, 본 발명은 장관 수송율을 향상시키는 것에 의해서, 장관 내용물의 체류가 원인이 되는 트림, 구역질, 오심, 구토, 조기 포만감, 체증, 소화불량, 위부ㆍ복부 팽만감 및 식욕부진 등의 증상, 특히 과음 혹은 과식에 의해 발생하는 이것들의 증상을 효과적으로 억제 혹은 해소할 수 있다. 게다가, 장관 수송율을 향상시켜, 장관 내용물의 체류를 해소하는 것에 의해서 소화촉진을 촉진시킬 수 있다.The gastrointestinal motility revitalization regulator of the present invention has the effect of improving the intestinal transport rate, as shown in Examples described later. Therefore, the gastrointestinal motility revitalization modulator of the present invention can solve various symptoms such as chronic gastritis, reflux esophagitis, abdominal hydrogen or pseudointestinal obstruction caused by retention of intestinal contents. In addition, the present invention improves the rate of intestinal transport, thereby causing symptoms such as burping, nausea, nausea, vomiting, premature satiety, congestion, indigestion, stomach and abdominal bloating, and loss of appetite caused by intestinal contents retention, in particular It can effectively suppress or eliminate these symptoms caused by heavy drinking or overeating. In addition, it is possible to promote digestion promotion by improving the intestinal transport rate and relieving the retention of intestinal contents.
이하에, 약리시험예, 제조예를 이용해서 본 발명을 구체적으로 설명하지만, 본 발명이 이들에 한정되는 것은 아니다.Hereinafter, the present invention will be described in detail using pharmacological test examples and production examples, but the present invention is not limited thereto.
하기 시험방법에 따라서, 장관 수송능에 영향을 주는 피험물질의 효과를 검토하였다.According to the following test method, the effect of the test substance on the intestinal transport ability was examined.
실시예 1Example 1
시험 전일에 절식시킨 5주령의 ddy계 웅성 마우스에, 0.5% 메틸셀룰로오스(이하, 'MC' 라고 한다)에 현탁시킨 메틸메티오닌설포늄클로라이드(1000㎎/㎏, 3000㎎/㎏)을 경구투여 하고, 15분 후에 활성탄소분말 현탁액을 경구투여 하였다. 또한 그 30분 후에 동물을 경추탈구로 죽이고, 유문부에서 회맹부까지의 장관을 적출하였다. 피험물질의 장관 수송능은 유문부에서의 탄소분말의 이동거리를 장관의 전체길이로 나누고, 장관 수송율로서 나타냈다. 또한 동일한 시험을 창출 건조 엑스S(300㎎/㎏, 원생약 환산량으로 3000㎎/㎏)에 대해서 수행하였다. 시험결과를 표 1에 나타내었다.Five-week-old male mice fasted the day before the test were orally administered with methylmethionine sulfonium chloride (1000 mg / kg, 3000 mg / kg) suspended in 0.5% methyl cellulose (hereinafter referred to as 'MC'). After 15 minutes, the activated carbon powder suspension was orally administered. After 30 minutes, the animal was killed by a cervical dislocation, and an intestine from the pyloric to the parliament was removed. The intestinal transport capacity of the test substance was expressed as the intestinal transport rate by dividing the moving distance of carbon powder in the pyloric region by the total length of the intestine. The same test was also performed on dry DX (300 mg / kg, 3,000 mg / kg in terms of the crude drug equivalent). The test results are shown in Table 1.
이상과 같이, MMSC의 투여에 의해 장관 수송율의 향상이 확인되고, 용량 의존적인 소화관 운동 부활 조정 작용이 확인되었다.As mentioned above, administration of MMSC confirmed the improvement of intestinal transport rate, and the dose-dependent gut exercise reactivation adjustment effect was confirmed.
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| KR101100901B1 (en) * | 2009-04-09 | 2012-01-02 | 주식회사 씨티네트웍스 | A sensing adapter |
| US10509185B2 (en) | 2016-04-27 | 2019-12-17 | Huawei Technologies Co., Ltd. | Optical connector with photodetector, adaptor for optical connector, and system |
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| JP4627574B2 (en) * | 1999-05-18 | 2011-02-09 | 進 黒澤 | Gastrointestinal motility improver |
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| KR101100901B1 (en) * | 2009-04-09 | 2012-01-02 | 주식회사 씨티네트웍스 | A sensing adapter |
| US10509185B2 (en) | 2016-04-27 | 2019-12-17 | Huawei Technologies Co., Ltd. | Optical connector with photodetector, adaptor for optical connector, and system |
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