KR100404443B1 - Pharmaceutical composition for treating gastritis and peptic ulcer - Google Patents
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- KR100404443B1 KR100404443B1 KR1019960045162A KR19960045162A KR100404443B1 KR 100404443 B1 KR100404443 B1 KR 100404443B1 KR 1019960045162 A KR1019960045162 A KR 1019960045162A KR 19960045162 A KR19960045162 A KR 19960045162A KR 100404443 B1 KR100404443 B1 KR 100404443B1
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Abstract
Description
본 발명은 위염과 위궤양 및 십이지장궤양 등 소화성궤양 치료제용 의약 조성물에 관한 것으로서, 본 발명의 의약 조성물은 쑥(Artemisia asiatica, A. mongolica, A. princeps, A. argyi) 추출물 그리고 위산분비억제효과를 나타내는 H2저해제, 프로톤펌프 저해제 또는 공격인자 역확산방지 및 헬리코박터 필로리 (Helicobacter pylori) 억제작용을 나타내는 콜로이드성 비스무스 화합물 등의 위염 및 소화성궤양 치료제용 약물로 이루어지며 위산에 의한 지속적 병소자극 및 동통에 대한 억제작용과 점액분비와 내인성 프로스타글란딘 합성촉진을 통한 위장관병변 치유 촉진작용을 동시에 나타내어 위염 및 소화성궤양 치료시 상승적 작용을 나타낸다.The present invention relates to a pharmaceutical composition for the treatment of peptic ulcer such as gastritis, gastric ulcer and duodenal ulcer, wherein the pharmaceutical composition of the present invention comprises extracts of Artemisia asiatica, A. mongolica, A. princeps, and A. argyi and gastric acid secretion inhibitory effect represents H 2 inhibitors, proton pump inhibitors or attack factor despread prevention and H. pylori (Helicobacter pylori) colloidal showing the inhibitory functional bismuth compounds such as gastritis and peptic ulcer therapeutic agent composed of a drug constantly lesions irritation and pain caused by gastric acid for And gastrointestinal tract lesion healing by promoting mucin secretion and endogenous prostaglandin synthesis, and exhibits a synergistic effect in the treatment of gastritis and peptic ulcer.
위는 식도를 통하여 들어온 음식물을 저장하고 소화되기 쉽게 잘게 부수며, 십이지장으로 음식물을 보내는 것을 조절하여 췌장효소의 분비와 조화를 이루어 효율적인 소화와 흡수가 되도록 하는 장기이다. 위는 음식물이 들어오면 이를 소화시키기 위해 강한 산인 위산을 분비하는데, 이때 점막보호층이 위산에 의해 위점막이손상받지 않도록 작용한다. 여러종류의 원인에 의해 위산의 분비가 항진되거나 위점막 보호층이 손상되었을 때 염증이 생기게 된다. 이 염증성 병변이 위점막에 한정되어 있을 때를 위염, 위점막을 뚫고 점막하조직과 근육층까지 궤양을 형성했을 때를 위궤양이라 한다. 또한 십이지장에서의 궤양을 십이지장궤양이라고 하며, 위궤양과 십이지장궤양을 소화성궤양으로 통칭하고 있다.The stomach is a long-term organ that stores the food from the esophagus, breaks it down easily, and controls the sending of food to the duodenum, thereby enabling efficient digestion and absorption by secretion and harmony of the pancreatic enzyme. The stomach secretes stomach acid, which is strong acid to digest when food comes in. At this time, the mucous membrane protects the gastric mucosa from being damaged by stomach acid. Inflammation occurs when the secretion of gastric acid is enhanced by various causes or when the gastric mucosal protective layer is damaged. When the inflammatory lesion is confined to the gastric mucosa, it is called gastric ulcer, when gastritis, ulcer formation through the gastric mucosa and submucosal tissue and muscle layer. Duodenal ulcers are called duodenal ulcers, and ulcers and duodenal ulcers are collectively called peptic ulcers.
이와같이 소화성 궤양이 공격인자의 항진이나 방어인자의 약화에 의해 유발된다고 하여, 이를 밸런스이론(Balance Theory)이라고 한다 (Gastroenterology pp. 420, 1963). 공격인자 중에는 위산, 소염제, 세균감염 등이 있고 방어인자에는 점액, 세포재생, 알칼리분비 등이 있다. 최근에는 공격인자 중 헬리코박터 필로리라는 세균의 감염이 중요한 원인으로 지목되고 있다 (Scan J. Gastroenterol 26(suppl) 6, 1991).This is called Balance Theory because peptic ulcers are caused by aggravation of attack factors or weakening of protective factors (Gastroenterology pp. 420, 1963). Among the attack factors, there are gastric acid, antiinflammatory agents, bacterial infection, and defense factors include mucus, cell regeneration, and alkaline secretion. Recently, Helicobacter pylori has been identified as an important cause of bacterial infection among the attack factors (Scan J. Gastroenterol 26 (suppl) 6, 1991).
위염과 소화성궤양의 치료제로는 제산제 (antacid), 산분비억제 목적의 H2저해제와 프로톤펌프저해제 (proton pump inhibitor), 또는 위점막보호제 등이 주류를 이루고 있으며, 최근 헬리코박터 필로리를 제거할 목적으로 항생제의 사용이 도입되고 있다. 제산제의 특징은 속효성이며 (New Eng J Med 298: 1041, 1978), 위내의 pH를 상승시켜 펩신 (pepsin)의 활성을 저하시킴으로써 약효를 나타낸다(New Eng J Med 274: 921, 1966). 그러나 무기물질 투여에 의해 변비 (J Int Med Res 6(suppl) 11, 1978), 설사 (Hepatogastroenterol 29: 135, 1982), 대사성 알칼로시스 (alkalosis) (Am J Dig Dis 11:413, 1966), 요로결석증 (Gastroenterologie21(suppl) 117, 1983) 등과 같은 부작용이 보고되어 있으며, 최근에는 제산제에 의한 산반동 (acid rebound) 현상 등이 문제시되고 있다(J Clin Gastroenterol 15(1): 37, 1992).Antacids, H 2 inhibitors and proton pump inhibitors, or gastric mucosal protective agents, which are used for the inhibition of acid secretion, are mainly used as therapeutic agents for gastritis and peptic ulcer. Recently, for the purpose of removing Helicobacter pylori The use of antibiotics has been introduced. The antacid is characterized by its short duration (New Eng J Med 298: 1041, 1978) and its efficacy by lowering the pH of the stomach to lower the activity of pepsin (New Eng J Med 274: 921, 1966). However, administration of inorganic substances has been associated with constipation (J Int Med Res 6 (suppl) 11, 1978), diarrhea (Hepatogastroenterol 29: 135, 1982), metabolic alkalosis (Am J Dig Dis 11: 413, 1966) (J Clin Gastroenterol 15 (1): 37, 1992). Recently, there has been a problem of acid rebound due to antacids (Gastroenterologie 21 (suppl) 117, 1983).
1977년 씨메티딘 (cimetidine)이 발매되면서부터 소화성궤양의 본격적 치료가 시작되었다고 볼 수 있다 (J Int Med Res 17(suppl) 9A, 1989). H2저해제인 씨메티딘의 유용성이 알려지면서 수종의 유도체가 개발되었는데 그 중 라니티딘(ranitidine), 파모티딘 (famotidine), 록사티딘 (roxatidine), 니자티딘(nizatidine) 등은 치료기간의 단축을 특징으로 임상에서 우수한 항궤양 효과를 나타내고 있으나 (Meth Find Exp Clin Pharmacol 11(suppl 1) 87, 1989, N Eng J Med 323: 1672, 1990), 투여종료후 높은 재발율이 문제시 되고 있다 (Drug Intell Clin Pharm 21: 493, 1987, Gut 30: 449, 1989). 이런 원인은 이들 공격인자 억제제에 의해 치유된 재생점막과 점막하조직이 정상 조직에 비해 약한 구조를 갖고 있어 약물투여 중지후에 다시 위산 등 공격인자에 쉽게 손상을 받기 때문인 것으로 알려져 있다 (J Clin Gastroenterol 11(suppl 1) S34, 1989).In 1977, when cimetidine was first released, a full-fledged treatment for peptic ulcers began (J Int Med Res 17 (suppl 9A, 1989)). As the availability of the H 2 inhibitor, cimetidine, has been known, a number of derivatives have been developed, including ranitidine, famotidine, roxatidine, nizatidine, (Meth Find Exp Exp Clin Pharmacol 11 (suppl 1) 87, 1989, N Eng J Med 323: 1672, 1990). However, a high recurrence rate has been a problem after administration Drug Intell Clin Pharm 21: 493, 1987, Gut 30: 449, 1989). This is because the mucous membrane and submucosal tissues healed by these attack factor inhibitors are weaker than normal tissues, and they are easily damaged by attack factors such as acidosis after drug administration (J Clin Gastroenterol 11 suppl 1) S34, 1989).
비교적 최근에 개발된 프로톤펌프 저해제로 오메프라졸 (omeprazole)과 란소프라졸 (lansoprazol) 등이 있으며, 위벽세포에서의 산분비를 최종단계에서 저해하여 강력한 산분비억제 효과를 나타내는 것으로 알려져 있으나 (Yale J Biol Med 65: 649, 1992), 이들 약제에 의한 궤양치유 환자에서도 재발율은 감소되지 않고 있으며, 연변, 설사, 발열, 두통, 피로감 등의 부작용이 보고되고 있다.A relatively recently developed proton pump inhibitor, omeprazole and lansoprazol, are known to inhibit acid secretion in the gastric wall cells at the final stage (Yale J Biol Med 65 : 649, 1992). The recurrence rate has not been reduced in patients with ulcer healing due to these agents, and side effects such as Yanbyeon, diarrhea, fever, headache and fatigue have been reported.
그러므로 위산분비억제를 목적으로 H2저해제와 프로톤펌프 저해제만을 사용할 경우 소화성궤양의 치료에 있어 가장 중요한 재발율 억제효과를 기대할 수 없다.Therefore, when H 2 inhibitor and proton pump inhibitor alone are used for the inhibition of gastric acid secretion, the most important inhibitory effect on recurrence of peptic ulcer is not expected.
위점막보호제의 경우 일반적으로 속효성이 적고 복용량이 많으며, 비교적 장기간 복용해야 하는 단점이 있으나 공격인자 억제제와는 다르게 재생점막이 정상과 유사하게 회복되는 것으로 알려져 있다 (Folia Pharmacol Japon 92: 389, 1988). 소화성궤양 재발의 원인으로는 현재 헬리코박터 필로리와 비스테로이드성 소염제가 중요한 역할을 하는 것으로 알려져 있는데 (Scan J Gastroenterol 26(suppl): 6, 1991) 이들 공격인자의 공격에 저항할 수 있도록 치유조직의 구조적 정상화 등 숙주요인 (host factor)의 회복도가 재발율을 낮추는데 매우 중요하다. 그러므로 소화성궤양의 치유기간 단축 뿐 아니라 재발율도 낮추는 즉, 궤양치유의 질 (quality of ulcer healing)을 향상시킬 수 있는 치료법의 도입이 절실한 상태이다.In the case of the gastric mucosal protective agent, it is known that the mucosal protective agent generally has a low short-acting effect, has a high dosage, and should be taken for a relatively long period of time. However, . Helicobacter pylori and non-steroidal anti-inflammatory drugs are known to play an important role in the recurrence of peptic ulcer (Scan J Gastroenterol 26 (suppl): 6, 1991) The recovery of the host factor, such as structural normalization, is very important for lowering the recurrence rate. Therefore, it is urgent to introduce treatment that can reduce the recurrence rate as well as shortening the duration of peptic ulcer healing, that is, improving the quality of ulcer healing.
본 발명자들은 위염 및 소화성궤양 치료제의 개발을 위하여 연구하고 있으며, 쑥 추출물이 위염 및 소화성궤양 치료효과가 있음을 발견하고 특허출원한 바 있다.The present inventors have been studying for the development of a therapeutic agent for gastritis and peptic ulcer, and found that the mugwort extract has an effect of treating gastritis and peptic ulcer, and has filed a patent application.
쑥은 국화과 (Compositae)에 속하는 다년생 초본식물로서 독특한 향기와 맛을 가지고 있다. 어린 잎은 식용으로서 쑥떡 등에 이용되어 왔고, 한방에서는 자궁을 따스하게 하여 자궁출혈, 임신중의 출혈 등에 효과가 있다고 알려져 있으며, 강장보혈, 부인병, 설사치료제로 쓰여 왔다 (東醫寶鑑). 쑥의 약리작용을 살펴보면,쑥의 물추출물은 혈액응고시간을 연장시키며 (약학회지 28(2): 69-77, 1984), 쑥으로부터 추출한 플라본 (flavone)은 항암활성이 있다고 보고되었으며 (Chem. Pharm. Bull. 32(2): 723, 1984), 혈소판응집 억제작용 (Zhongguo Zhongyao Zazhi, 17(6): 353, 1992), 항알러지효과 (Chem. Pharm. Bull. 39(8): 2077-2081 1991) 등도 보고된 바 있다.Mugwort is a perennial herbaceous plant belonging to Compositae and has a unique aroma and taste. Young leaves have been used for food such as mugwort cake and have been known to be effective for bleeding of uterus and bleeding during pregnancy by warming the uterus in one room, and it has been used as a treatment for hypertension, gynecological diseases and diarrhea (东 醫 寶 鑑). As the pharmacological action of mugwort, the water extract of mugwort prolongs blood coagulation time (Pharmacology Journal 28 (2): 69-77, 1984). Flavone extracted from mugwort has been reported to have anticancer activity (Chem. Pharm. Bull. 39 (8): 2077-7, 1992), platelet aggregation inhibitory action (Zhongguo Zhongyao Zazhi, 17 (6) 2081, 1991).
본 발명자 등은 쑥에 대한 집중적인 연구를 계속해 오고 있으며, 특히 우리나라 자생쑥의 약효를 밝히기 위해 노력하여 오던 중, 쑥으로부터 상기한 약리작용 외에 위점막보호 효과가 있음을 발견하고 쑥 추출물 (product by process) 및 이 추출물의 위장질환 치료제로서의 용도를 특허출원한 바 있다 (특허출원 제 95-21957호). 또한 쑥으로부터 자세오시딘 (jaceosidin)과 유파틸린 (eupatilin)을 분리하고, 이 유파틸린과 자세오시딘이 위장질환 치료제로서 효과가 있음을 밝혔으며 (특허출원 제 94-147호, 제 94-39337호), 현재까지 특효약이 없는 것으로 알려진 염증성 장질환에 대해서도 유효함을 밝힌 바 있다 (특허출원 제 96-28230호).The inventors of the present invention have continued intensive research on mugwort. Especially, while trying to clarify the medicinal properties of native mugwort, the inventors found that mugwort has a gastric mucosal protective effect other than the above-mentioned pharmacological action, (Patent Application No. 95-21957), and the use of the extract as a therapeutic agent for gastrointestinal diseases (Patent Application No. 95-21957). In addition, jaceosidin and eupatilin were separated from mugwort, and it was found that this oil tiline and posture oocidine were effective as therapeutic agents for gastrointestinal diseases (Patent Application No. 94-147, 94-39337 (Patent Application No. 96-28230), which has been known to be effective against inflammatory bowel disease, which is known to have no specific drug.
본 발명자들은 계속된 연구를 통해, 쑥 추출물이 위산분비에는 영향을 미치지 않으며, 점액분비를 촉진하는 등 점막보호효과를 나타냄을 발견하였으며, 본 출원인에 의해 이미 특허출원된 바와 같이 쑥 추출물 (특허출원 제 95-21957호)이 자체로서 위염 및 소화성궤양에 대한 치료효과를 나타낼 뿐만 아니라 종래의 위염 및 소화성궤양 치료제용 약물인 위산분비 억제제인 H2차단제 및 프로톤펌프 저해제와 콜로이드성 비스무스 화합물과 병용할 경우 매우 우수한 상승적 치료효과(synergy)를 나타냄을 발견하고 본 발명을 완성하였다.The inventors of the present invention found through continuous research that mugwort extract does not affect gastric acid secretion and exhibits a mucosal protective effect such as promoting mucus secretion. As described in the patent application already filed by the present applicant, 95-21957) itself not only shows therapeutic effects on gastritis and peptic ulcer, but also can be used in combination with H 2 blocker and proton pump inhibitor, which are gastric acid secretion inhibitors, which are drugs for gastritis and peptic ulcer treatment, and colloidal bismuth compound The present invention provides a synergistic synergistic effect.
본 발명은 쑥 추출물과 위염 및 소화성궤양 치료제용 약물로 이루어지는 의약 조성물에 관한 것이다.The present invention relates to a pharmaceutical composition comprising mugwort extract, a drug for treating gastritis and peptic ulcer, and the like.
본 발명의 위염 및 소화성궤양 치료제용 약물에는 H2차단제, 프로톤펌프 저해제 및 콜로이드성 비스무스 화합물이 포함될 수 있다.The drug for treating gastritis and peptic ulcer of the present invention may include an H 2 blocker, a proton pump inhibitor and a colloidal bismuth compound.
본 발명의 의약 조성물은 쑥 추출물과 H2차단제로 구성될 수 있다.The pharmaceutical composition of the present invention may be composed of mugwort extract and H 2 blocker.
본 발명의 의약 조성물은 쑥 추출물과 프로톤펌프 저해제로 구성될 수 있다.The pharmaceutical composition of the present invention may be composed of mugwort extract and proton pump inhibitor.
본 발명의 의약 조성물은 쑥 추출물과 콜로이드성 비스무스 화합물로 구성될 수 있다.The pharmaceutical composition of the present invention may be composed of mugwort extract and colloidal bismuth compound.
본 발명에 사용되는 H2차단제에는 파모티딘, 라니티딘, 씨메티딘 등이 포함될 수 있으며, 프로톤펌프 저해제에는 오메프라졸이 포함될 수 있으며, 콜로이드성 비스무스 화합물에는 비스무스 섭시트레이트가 포함될 수 있다.The H 2 blocking agent used in the present invention may include famotidine, ranitidine, cimetidine, etc. The proton pump inhibitor may include omeprazole, and the colloidal bismuth compound may include a bismuth supercritical rate.
본 발명에 사용된 쑥 추출물의 제조방법은 본 발명의 출원인이 기출원한 특허출원(특허출원 제 95-22957호)에 상세히 기록되어 있으며, 그 내용은 다음의 참고예와 같이 요약될 수 있다.The method for producing the mugwort extract used in the present invention is described in detail in a patent application (Patent Application No. 95-22957) filed by the applicant of the present invention, the contents of which can be summarized as follows.
<참고예 1>≪ Reference Example 1 &
세절한 쑥잎 100g을 70% 에탄올 1l로 상온에서 24시간씩 2회 냉침하고 추출여액을 감압농축한 후 동결건조하여 고형분 10.8g을 얻는다. 고형분 중 유파틸린의 함량은 0.449%, 자세오시딘의 함량은 0.277%였다.100 g of dried wormwood leaves are frozen twice with 1 l of 70% ethanol for 24 hours at room temperature, and the extracted filtrate is concentrated under reduced pressure and lyophilized to obtain a solid content of 10.8 g. The content of milk tilline was 0.449% and the content of postural osteine was 0.277%.
<참고예 2><Reference Example 2>
세절한 쑥잎 100g을 70% 에탄올 1l로 4시간씩 2회 환류추출하고 추출여액을 감압농축한 후 동결건조하여 고형분 16.2g을 얻는다. 고형분중 유파틸린의 함량은 0.412%, 자세오시딘의 함량은 0.225%였다.100 g of the fine wormwood leaves are refluxed twice with 4 liters of 70% ethanol for 4 hours. The extract is concentrated under reduced pressure and lyophilized to obtain a solid content of 16.2 g. The content of milk tilline was 0.412% and the content of postural osteine was 0.225%.
<참고예 3><Reference Example 3>
세절한 쑥잎 100g을 70% 에탄올 1l로 상온에서 4시간씩 2회 초음파 추출하고 추출여액을 감압농축한 후 동결건조하여 고형분 12.8g을 얻는다. 고형분중 유파틸린의 함량은 0.443%, 자세오시딘의 함량은 0.252%였다.100 g of dried wormwood is ultrasonically extracted with 1 l of 70% ethanol for 4 hours at room temperature for 2 hours, and the extracted filtrate is concentrated under reduced pressure and lyophilized to obtain a solid content of 12.8 g. The content of milk tiline was 0.443% and the content of postural osteine was 0.252%.
<참고예 4><Reference Example 4>
세절한 쑥잎 100g을 90% 에탄올 1l로 상온에서 24시간씩 2회 냉침하고 추출여액을 감압농축한 후 동결건조하여 고형분 7.2g을 얻는다. 고형분중 유파틸린의 함량은 0.734%, 자세오시딘의 함량은 0.513% 였다.100 g of the fine wormwood leaves are frozen twice with 1 liter of 90% ethanol for 24 hours at room temperature, and the extracted filtrate is concentrated under reduced pressure and lyophilized to obtain 7.2 g of a solid. The content of milk tilline was 0.734% and the content of posture osteine was 0.513%.
<참고예 5><Reference Example 5>
세절한 쑥잎 100g을 90% 에탄올 1l로 4시간씩 2회 환류추출하고 추출여액을 감압농축한 후 동결건조하여 고형분 13.4g을 얻는다. 고형분 중 유파틸린의 함량은 0.823%, 자세오시딘의 함량은 0.493%였다.100 g of the fine wormwood leaves are refluxed for 2 hours with 1 l of 90% ethanol for 4 hours. The extract is concentrated under reduced pressure and lyophilized to obtain a solid content of 13.4 g. The content of milk tiline was 0.823% and the content of posture osteine was 0.493% in the solid contents.
<참고예 6><Reference Example 6>
세절한 쑥잎 100g을 90% 에탄올 1l로 상온에서 4시간씩 2회 초음파추출하고추출여액을 감압농축한 후 동결건조하여 고형분 9.7g을 얻는다. 고형분중 유파틸린의 함량은 0.896%, 자세오시딘의 함량은 0.487%였다.100 g of the wormwood leaves are ultrasonically extracted twice with 1 l of 90% ethanol for 4 hours at room temperature. The extract is concentrated under reduced pressure and lyophilized to obtain 9.7 g of a solid. The content of milk tiline and porcine osteidine in solid contents were 0.896% and 0.487%, respectively.
<참고예 7><Reference Example 7>
세절한 쑥잎 100g을 95% 에탄올 1l로 상온에서 24시간씩 2회 냉침하고 추출여액을 감압농축한 후 동결건조하여 고형분 5.0g을 얻는다. 고형분중 유파틸린의 함량은 1.010%, 자세오시딘의 함량은 0.640%였다.100 g of dried wormwood leaves are cooled with 1 l of 95% ethanol at room temperature for 24 hours twice, and the extracted filtrate is concentrated under reduced pressure and lyophilized to obtain 5.0 g of a solid. The content of milk tilline was 1.010% and the content of posture osteine was 0.640%.
<참고예 8><Reference Example 8>
세절한 쑥잎 100g을 95% 에탄올 1l로 4시간씩 2회 환류추출하고 추출여액을 감압농축한 후 동결건조하여 고형분 10.3g을 얻는다. 고형분중 유파틸린의 함량은 0.994%, 자세오시딘의 함량은 0.565%였다.100 g of the fine wormwood leaves are refluxed for 2 hours with 1 l of 95% ethanol for 4 hours. The extracted filtrate is concentrated under reduced pressure and lyophilized to obtain a solid content of 10.3 g. Among the solids, the content of milk tilline was 0.994% and the content of postural osteine was 0.565%.
<참고예 9><Reference Example 9>
세절한 쑥잎 100g을 95% 에탄올 1l로 상온에서 4시간씩 2회 초음파 추출하고 추출여액을 감압농축한 후 동결건조하여 고형분 9.7g을 얻는다. 고형분중 유파틸린의 함량은 0.987%, 자세오시딘의 함량은 0.534%였다.100 g of the fine wormwood leaves are ultrasonically extracted with 1 l of 95% ethanol for 4 hours at room temperature for 2 hours, and the extracted filtrate is concentrated under reduced pressure and lyophilized to obtain a solid content of 9.7 g. The content of milk tiline was 0.987% and the content of posture oystin was 0.534%.
<참고예 10><Reference Example 10>
세절한 쑥잎 100g을 100% 에탄올 1l로 상온에서 24시간씩 2회 냉침하고 추출여액을 감압농축한 후 동결건조하여 고형분 5.2g을 얻는다. 고형분중 유파틸린의 함량은 1.284%, 자세오시딘의 함량은 0.649%였다.100 g of the fine wormwood leaves are cooled with 1 l of 100% ethanol for 24 hours at room temperature for 2 hours, and the extracted filtrate is concentrated under reduced pressure and freeze-dried to obtain 5.2 g of a solid. The content of milk tiline was 1.284% and the content of posture osteine was 0.649%.
<참고예 11><Reference Example 11>
세절한 쑥잎 100g을 100% 에탄올 1l로 4시간씩 2회 환류추출하고 추출여액을감압농축한 후 동결건조하여 고형분 8.9g을 얻는다. 고형분중 유파틸린의 함량은 1.129%, 자세오시딘의 함량은 0.638%였다.100 g of the fine wormwood leaves are refluxed with 1 l of 100% ethanol for 4 hours twice, and the extracted filtrate is concentrated under reduced pressure and lyophilized to obtain a solid content of 8.9 g. In the solids, the content of milk tiline was 1.129% and the content of porcine oystine was 0.638%.
<참고예 12><Reference Example 12>
세절한 쑥잎 100g을 100% 에탄올 1l로 상온에서 4시간씩 2회 초음파 추출하고 추출여액을 감압농축한 후 동결건조하여 고형분 7.1g을 얻는다. 고형분중 유파틸린의 함량은 0.978%, 자세오시딘의 함량은 0.541%였다.100 g of dried wormwood leaves are ultrasonically extracted with 1 l of 100% ethanol for 4 hours at room temperature. The extract is concentrated under reduced pressure and lyophilized to obtain 7.1 g of a solid. The content of milk tilline was 0.978% and the content of posture osteine was 0.541% in the solid contents.
<참고예 13><Reference Example 13>
세절한 쑥잎 100g을 95% 에탄올 800ml로 상온에서 24시간씩 2회 냉침하고 추출여액을 1/150로 감압농축한 후 유당 7.0g, 옥수수전분 3.0g을 가하여 연합하고 20메쉬 체를 통과시켜 과립화한 다음 80℃에서 열풍건조하여 고형분 14.8g을 얻는다. 고형분중 유파틸린의 함량은 0.429%, 자세오시딘의 함량은 0.231%였다.100 g of dried wormwood leaves were cooled with 800 ml of 95% ethanol for 24 hours at room temperature, and the extracted filtrate was concentrated under reduced pressure to 1/150, and then 7.0 g of lactose and 3.0 g of corn starch were added thereto and passed through a 20- Followed by hot air drying at 80 DEG C to obtain a solid content of 14.8 g. The content of milk tilline was 0.429% and the content of posture osteine was 0.231%.
<참고예 14><Reference Example 14>
세절한 쑥잎 100g을 95% 에탄올 800ml로 상온에서 24시간씩 2회 냉침하고 추출여액을 1/100로 감압농축한 후 텍스트린 0.5g을 고르게 분산시킨 다음 분무건조하여 고형분 13.9g을 얻는다. 고형분중 유파틸린의 함량은 0.417%, 자세오시딘의 함량은 0.277%였다.100 g of dried wormwood leaves are cooled with 800 ml of 95% ethanol for 24 hours at room temperature twice, and the extracted filtrate is concentrated under reduced pressure to 1/100, then 0.5 g of texturin is evenly dispersed and then spray dried to obtain 13.9 g of solid content. The content of milk tilline was 0.417% and the content of postural osteine was 0.277% in the solid contents.
<참고예 15>≪ Referential Example 15 >
세절한 쑥잎 100g을 95% 에탄올 800ml로 상온에서 24시간씩 2회 냉침하고 추출여액을 감압농축한 후 동결건조하여 고형분 5.0g을 얻는다. 고형분중 유파틸린의 함량은 1.312%, 자세오시딘의 함량은 0.667%였다.100 g of dried wormwood leaves are cooled with 800 ml of 95% ethanol at room temperature for 24 hours twice, and the extracted filtrate is concentrated under reduced pressure and lyophilized to obtain 5.0 g of a solid. Among the solids, the content of milk tiline was 1.312% and the content of porcine oysteine was 0.667%.
<참고예 16><Reference Example 16>
세절한 쑥잎 100g을 물 1,000ml로 상온에서 24시간씩 2회 냉침하고 여액은 버린다. 추출잔사에 100% 에탄올 700ml를 가하고 24시간 냉침하여 여과하고 다시 70% 에탄올 700ml를 가하고 24시간 냉침하여 여과한다. 추출여액을 합하여 감압농축한 후 동결건조하여 고형분 4.7g을 얻는다. 고형분중 유파틸린의 함량은 1.274%, 자세오시딘의 함량은 0.673%였다.100 g of the fine wormwood leaves are cooled with 1,000 ml of water twice at room temperature for 24 hours, and the filtrate is discarded. 700 ml of 100% ethanol is added to the extracted residue, the mixture is cooled for 24 hours, filtered, and 700 ml of 70% ethanol is added. The extracted filtrate was combined, concentrated under reduced pressure, and then lyophilized to obtain a solid content of 4.7 g. The content of milk tiline was 1.274% and the content of posture osteine was 0.673%.
이하 인위적으로 유도된 위염 및 소화성궤양 동물모델에서 쑥 추출물과 H2저해제, 프로톤펌프 저해제 또는 콜로이드성 비스무스 화합물로 이루어지는 의약 조성물이 위염 및 소화성궤양 치료의 질 (quality)에 미치는 영향을 실시예 에 의거 상세히 설명하고자 한다. 본 발명의 실시예는 본 발명의 내용을 예시하는 것일 뿐, 본 발명의 내용이 이들에 의해 한정되는 것은 아니다.The effect of the pharmaceutical composition comprising the mugwort extract, the H 2 inhibitor, the proton pump inhibitor or the colloidal bismuth compound on the quality of gastric and peptic ulcer treatment in an artificially induced gastritis and peptic ulcer animal model is shown in the examples I will explain in detail. The embodiments of the present invention are illustrative of the contents of the present invention, and the contents of the present invention are not limited thereto.
I. 약효시험I. Drug test
상기한 참고예에서 얻은 쑥 추출물과 H2저해제, 프로톤펌프 저해제 또는 클로이드성 비스무스 화합물로 이루어지는 의약 조성물이 위염 및 소화성궤양 치료의 질에 미치는 상승작용확인은 상승작용검정에 널리 사용되는 통계법인 오카베(Okabe)법 (Pharmacometrics 12: 759, 1976)과 최근 새롭게 알려진 통계검정법 라스카(Laska)법 (Biometrics 50: 834, 1994)을 이용하였다.The ascertaining effect of the pharmaceutical composition comprising the mugwort extract, the H 2 inhibitor, the proton pump inhibitor or the cystic bismuth compound on the quality of treatment of gastritis and peptic ulcer obtained in the above Referential Example can be confirmed by the statistical method of Okabe The Okabe method (Pharmacometrics 12: 759, 1976) and the recently introduced statistical test method Laska method (Biometrics 50: 834, 1994) were used.
오카베법에서의 상승작용 검증은 각 약물을 단독투여시 발생하는 궤양발생율(incidence)을 곱하여 얻어지는 값이 약물병용시 얻어지는 발생율보다클 경우 상승작용이 발생한 것으로 판정하며, 본 실시예에서의 각 약물의 용량은 50%의 유효율을 나타내는 ED50치를 사용하였다. 라스카법에서의 상승작용검정은 각 약물의 ED50을 구한 다음 아래의 각 군중 제 1군에서의 약효가 편측 t검정 (one-side Student t-test)시 제 2,3군에 비해 유의하게 높을 경우 상승효과로 인정한다.The synergy test in the Okabe method is judged to be a synergistic effect when the value obtained by multiplying the incidence of ulcers occurring when each drug is administered alone is greater than the incidence rate obtained when the drug is used in combination. An ED 50 value indicating a 50% effective dose was used. The synergistic assays in the Laskar method were significantly higher than those of the second and third groups in the one-side Student t-test for each drug group in the first group after obtaining the ED 50 of each drug It is recognized as a synergistic effect.
제1군 : 약물 A, B 병용군(약물 A의 1/2 ED50+ 약물 B의 1/2 ED50)Group 1: Drug A, B combined use group (ED 50 of the drug A 1/2 + 1/2 Drug ED 50 of B)
제2군 : 약물 A투여군(약물 A의 1/2 ED50+ 약물 B의 1/2 ED50×1/r), r=0.25(기대치)Group 2: Drug A administered group (1/2 ED 50 of drug A + 1/2 ED 50 x 1 / r of drug B), r = 0.25 (expected value)
제3군 : 약물 B투여군(약물 A의 1/2 ED50× r + 약물 B의 1/2 ED50), r=0.25(기대치)Group 3: Drug B treated group (1/2 ED 50 x r of drug A + 1/2 ED 50 of drug B), r = 0.25 (expected value)
<실시예 1> 쑥 추출물과 HExample 1: Mugwort extract and H 22 저해제와의 상승작용Synergism with inhibitors
인도메타신(indomethacin)에 의한 위병변에 대해 상기한 라스카법(Biometrics 50: 834, 1994)을 이용하여 H2저해제와 쑥 추출물과의 상승작용을 검토하였다. H2저해제로는 파모티딘, 라니티딘 및 씨메티딘을 사용하였다. 7주령의 웅성 랫드를 24시간 동안 절식한 다음 각 약물을 경구투여하고 1시간후에 인도메타신 40mg/kg을 경구투여하였다. 인도메타신 투여후 6시간에 모든 동물을 도살하여 위를 적출하고 궤양면적으로 계측한 다음 상승작용을 확인하였다. 시험결과는 표 1∼3과 같다.The synergistic action of the H 2 inhibitor with the mugwort extract was examined using the Laskar method (Biometrics 50: 834, 1994) for indomethacin-induced gastric lesions. Famotidine, ranitidine and cimetidine were used as H 2 inhibitors. Seven weeks old male rats were fasted for 24 hours, and oral administration of each drug was followed by oral administration of indomethacin 40 mg / kg 1 hour later. All animals were slaughtered 6 hours after the administration of indomethacin, the stomach was excised and the ulcer area was measured and ascertained. The test results are shown in Tables 1 to 3.
쑥 추출물과 파모티딘으로 이루어지는 의약 조성물이 인도메타신 유발 위궤양에 미치는 상승작용은 표 1에, 쑥 추출물과 라니티딘으로 이루어지는 의약 조성물이 미치는 상승작용은 표 2에, 쑥 추출물과 씨메티딘으로 이루어지는 의약 조성물이 미치는 상승작용은 표 3에 나타내었다.The synergistic action of the medicinal composition comprising mugwort extract and famotidine on the indomethacin-induced gastric ulcer is shown in Table 1, and the synergistic action of the medicinal composition comprising mugwort extract and ranitidine is shown in Table 2. The synergistic action of the mugwort extract and cimetidine The synergistic action of the pharmaceutical composition is shown in Table 3.
[표 1][Table 1]
인도메타신유발 위궤양에 대한 쑥 추출물과 파모티딘의 상승작용-라스카법Synergism between Mugwort extract and famotidine on indomethacin-induced gastric ulcer
[표 2][Table 2]
인도메타신유발 위궤양에 대한 쑥 추출물과 라니티딘의 상승작용-라스카법Synergistic Action of Mugwort Extract and Ranitidine on Indomethacin-Induced Gastric Ulcer
[표 3][Table 3]
인도메타신유발 위궤양에 대한 쑥 추출물과 씨메티딘의 상승작용Synergistic Effect of Mugwort Extract and Cimetidine on Indomethacin-Induced Gastric Ulcer
상기 표 1, 표 2, 표 3에서 알 수 있는 바와 같이 쑥 추출물과 파모티딘, 쑥 추출물과 라니티딘, 쑥 추출물과 씨메티딘으로 이루어지는 의약 조성물은 인도메타신으로 유발한 위궤양 모델에서 뛰어난 상승효과를 나타냄을 알 수 있다.As can be seen from Tables 1, 2 and 3, the pharmaceutical composition comprising mugwort extract, famotidine, mugwort extract, lanitidine, mugwort extract and cimetidine showed excellent synergistic effect in the indomethacin- . ≪ / RTI >
또한 동일한 인도메타신 위궤양모델에서 상기한 오카베법(Pharmacometrics12: 759, 1976)에 의한 쑥 추출물과 파모티딘과의 상승작용을 표 4에 나타내었다.The synergistic action of mugwort extract and famotidine by the above-mentioned Okabe method (Pharmacometrics 12: 759, 1976) in the same indomethacin gastric ulcer model is shown in Table 4.
[표 4][Table 4]
인도메타신유발 위궤양에 대한 쑥 추출물과 파모티딘의 상승작용-오카베법Synergistic action of mothi extract and famotidine on indomethacin-induced gastric ulcer - Okabe method
상기 표 4에서 알 수 있는 바와 같이 쑥 추출물과 파모티딘으로 이루어지는 의약 조성물은 모든 용량군에서 인도메타신으로 유발한 위궤양 모델에서 뛰어난 효과를 나타냄을 알 수 있다.As can be seen from the above Table 4, the pharmaceutical composition comprising mugwort extract and famotidine shows excellent effects in the indomethacin-induced gastric ulcer model in all dose groups.
<실시예 2> 쑥 추출물과 프로톤펌프 저해제와의 상승작용Example 2 Synergistic Effect of Mugwort Extract and Proton Pump Inhibitor
무수에탄올 (absolute ethanol)에 의한 위병변에 대해 상기한 오카베법(Pharmacometrics 12: 759, 1976)을 이용하여 대표적 프로톤펌프 저해제인 오메프라졸 (omeprazole)과 쑥 추출물과의 상승작응을 검토하였다. 7주령의 웅성랫드를 24시간동안 절식한 다음 각 약물을 경구투여하고 1시간후에 무수에탄올을 마리당 1.5ml로 경구투여하였다. 에탄올 투여 1시간 후에 모든 동물을 도살하여 위를 적출하고 병변면적을 계측한 다음 상승작용을 확인하였다. 시험결과는 표 5에 나타내었다.The uptake of omeprazole and mugwort extract, which are representative proton pump inhibitors, was investigated using the above-mentioned Okabe method (Pharmacometrics 12: 759, 1976) for absolute ethanol-induced gastric lesions. Seven-week-old male rats were fasted for 24 hours and each drug was orally administered. After 1 hour, anhydrous ethanol was orally administered at 1.5 ml per mouse. After 1 hour of ethanol administration, all animals were slaughtered and the stomach was excised and the lesion area was measured and ascertained synergy. The test results are shown in Table 5.
[표 5][Table 5]
무수에탄올유발 위병변에 대한 쑥 추출물과 오메프라졸의 상승작용-오카베법Synergistic Action of Mugwort Extract and Omeprazole on Anhydrous Ethanol-Induced Gastric Lesions - Okabe Method
상기 표 5에서 볼 수 있는 바와 같이, 쑥 추출물과 오프라메졸로 이루어지는 의약 조성물은 모든 용량군에서 무수에탄올로 유발한 위병변 부위를 상승적으로 축소시키고, 병변 발현율을 상승적으로 감소시킴을 알 수 있다.As can be seen from Table 5, it can be seen that the pharmaceutical compositions comprising mugwort extract and Oprameseol synergistically reduce gastric lesion sites induced by anhydrous ethanol in all the dose groups and synergistically decrease lesion expression rates.
<실시예 3> 쑥 추출물과 콜로이드성 비스무스 화합물과의 상승작용Example 3 Synergism between Mugwort Extract and Colloidal Bismuth Compound
에탄올-염산 (ethanol-HCl)에 의한 위병변에 대해 상기한 오카베법(Pharmacometrics 12: 759, 1976)을 이용하여 대표적 콜로이드성 비스무스 화합물(colloidal bismuth)인 비스무스 섭시트레이트 (bismuth subcitrate)와 쑥 추출물과의 상승작용을 검토하였다. 7주령의 웅성 랫드를 24시간 동안 절식한 다음 각 약물을 경구투여하고 1시간후에 에탄올-염산 혼합액을 마리당 1.0ml로 경구투여하였다. 에탄올-염산투여 1시간 후에 모든 동물을 도살하여 위를 적출하고 병변면적을 계측한 다음 상승작용을 확인하였다. 시험결과는 표 6에 나타내었다.The colloidal bismuth bismuth subcitrate and the mugwort extract were prepared by using the above-mentioned Okabe method (Pharmacometrics 12: 759, 1976) for stomach lesions by ethanol-HCl. . Seven weeks old male rats were fasted for 24 hours and each drug was orally administered. After 1 hour, the ethanol / hydrochloric acid mixture was orally administered at 1.0 ml per mouse. One hour after the administration of ethanol-hydrochloric acid, all animals were slaughtered and the stomach was excised and the area of the lesion was measured to confirm the synergy. The test results are shown in Table 6.
[표 6][Table 6]
에탄올-염산유발 위병변에 대한 쑥 추출물과 비스무스섭시트레이트의 상승작용-오카베법Synergistic Effect of Mugwort Extract and Bismuth Supercritice on Ethanol-Hydrochloric Acid-Induced Gastric Lesions-Okabe Method
상기 표 6에서 알 수 있는 바와 같이, 쑥 추출물과 비스무스 섭시트레이트로 이루어지는 의약 조성물은 모든 용량군에서 에탄올-염산으로 유발한 위궤양 면적을 상승적으로 축소시키고 병변 발현율을 상승적으로 감소시킴을 알 수 있다.As can be seen from Table 6, it can be seen that the pharmaceutical compositions comprising mugwort extract and bismuth suppository rate synergistically reduce the area of gastric ulcer caused by ethanol-hydrochloric acid in all dose groups and synergistically decrease the lesion expression rate .
Ⅱ. 궤양치유의 질에 미치는 쑥 추출물의 영향Ⅱ. Effect of Mugwort Extract on the Quality of Ulcer Healing
<실시예 4> 쑥추츨물과 H≪ Example 4 > 22 저해제와의 상승작용Synergism with inhibitors
실험적 아만성 궤양모델로 가장 널리 이용되는 초산-유발 위궤양의 치유의 질 (quality of ulcer healing)에 미치는 쑥 추출물의 영향을 조사하였다. 초산에 의한 위궤양 모델은 표준적 시험법에 의거 (Gastroenterology 95: 636, 1988), 6주령의 랫드를 마취시킨 후 개복하여 위장장막에 초산을 접촉시킨 후 다시 봉합하여 작성하였다. 궤양유발 1일 후부터 1일 1회 4주간 약물을 경구투여하였으며, 약물투여 2주 및 4주에 각 군의 일부를 부검하여 위를 적출하고 궤양치유정도를 평가하고 (Gastroenterologica japonica 17(6): 530, 1982, J Clin Gastroenterol 13(suppl 1): S42, 1991), 크러스칼-월리스 (Cruskal-Wallis) 분산분석후 던(Dunn)테스트를 통해 다중비교를 하였다. 시험결과는 표 7 및 표 8과 같다.The effects of mugwort extract on the quality of ulcer healing of acetic acid - induced gastric ulcer, the most widely used experimental subchronic ulcer model, were investigated. The gastric ulcer model by acetic acid was prepared by anesthetizing 6-week-old rats according to the standard method (Gastroenterology 95: 636, 1988), contacting acetic acid to the gastrointestinal membranes and then suturing again. After the first day of ulcer induction, the drug was orally administered once a day for 4 weeks. At 2 and 4 weeks after the drug administration, a portion of each group was autopsied to excise the stomach and evaluate the ulcer healing level (Gastroenterologica japonica 17 (6) 530, 1982, J Clin Gastroenterol 13 (suppl 1): S42, 1991) and Dunn test after Cruskal-Wallis ANOVA. The test results are shown in Table 7 and Table 8.
[표 7][Table 7]
약물투여 2주의 궤양치유정도Drug administration 2 weeks Severity of ulcer healing
[표 8][Table 8]
약물투여 4주의 궤양치유정도Drug administration 4 weeks Severity of ulcer healing
상기 표 7 및 표 8에서 알 수 있는 바와 같이 약물투여 2주에 재생점막의 파스-알시안블루 (PAS-AB)염색도 및 궤양저부의 섬유화정도에서 대조군에 비해 라니티딘 단독투여군에서는 유의한 개선효자를 나타내지 않았으나 참고예 15의 쑥 추출물 투여군과 쑥 추출물 및 라니티딘의 병용투여군에서는 점막충실도 및 섬유화 정도에서 유의한 회복성을 나타내었다. 또한 재생점막의 성숙도를 나타내는 파스-알시안블루 염색에서도 유의성은 없었으나 대조군에 비해 파스염색성이 강해 성숙도가 높은 것으로 나타났다. 투여 4주후에 평가한 조직소견에서 치유된 궤양저부의 섬유화 (세포치밀도)정도는 각 군간 차이를 나타내지 않았으나 궤양저부의 혈관신생 (vasculization)정도와 재생점막의 정상화 (normalization)정도는 쑥 추출물 투여군과 쑥 추출물 및 라니티딘 병용군에서 대조군에 대비하여 유의한 회복도를 나타내었다.As can be seen in Tables 7 and 8, the PAS-AB staining of the regenerated mucosa at 2 weeks after administration of the drug and the degree of fibrosis at the bottom of the ulcer were significantly improved in ranitidine alone group But the mugwort extract-treated group and the mugwort extract-treated ranitidine group of Reference Example 15 showed significant mucosal fidelity and fibrosis recovery. In addition, there was no significant difference in PAS-Alcian blue staining, indicating maturity of regenerated mucosa, but maturity was high due to strong PAS staining compared with control. The degree of fibrosis (cell density) of the healed ulcer bottom at 4 weeks after administration was not different between the groups, but the degree of vasculization and normalization of regenerated mucosa at the bottom of ulcer And mugwort extract and ranitidine showed a significant recovery in comparison with the control group.
이상과 같은 결과는 쑥 추출물이 다양한 위염 및 소화성궤양의 동물모델에 비해 H2저해제, 프로톤펌프 저해제 또는 콜로이드성 비스무스 화합물과 병용시 상승적으로 약효를 나타냄을 의미하며, 이들 약제와 쑥 추출물을 병용함으로써 우수한 치료효과와 숙주요인 회복도증가에 따른 재발율억제 뿐만 아니라 복용량의 감소 등에 의해 전술한 이들 약제의 부작용도 경감시키는 등 안전하고 유용한 소화성궤양 치료법의 도입이 가능함을 의미한다.These results indicate that the mugwort extract exhibits a synergistic effect when used in combination with an H 2 inhibitor, a proton pump inhibitor or a colloidal bismuth compound in comparison with an animal model of gastritis and peptic ulcer. By combining these drugs with mugwort extract It is possible to introduce safe and useful peptic ulcer treatment such as reduction of recurrence rate due to excellent therapeutic effect and recovery of host factors as well as reduction of side effects of these drugs by decreasing dose.
이하 본 발명에 따르는 제제실시예로써 본 발명을 구체화하고자 한다. 본 발명의 내용이 이들 제제실시예에 의해 한정되는 것은 아니며, 제제실시예는 여러 가지 변형이 가능하다.Hereinafter, the present invention will be described as an example of the formulation according to the present invention. The contents of the present invention are not limited to these formulation examples, and the formulation examples can be modified in various ways.
<제제실시예 1> 연질캅셀제의 제조≪ Formulation Example 1 > Preparation of soft capsule
약전 제제총칙중 연질캅셀의 제법에 따라 1 캅셀중 다음의 성분함량이 함유되도록 제조한다.In accordance with the general procedure for the preparation of soft capsules, one capsule contains the following ingredients.
95% 에탄올 냉침 쑥 추출물 125.0 mg95% Ethanol wormwood extract 125.0 mg
파모티딘 10.0 mgFamotidine 10.0 mg
콩기름 182.0 mgSoybean oil 182.0 mg
황납 42.5 mgYellow phosphorus 42.5 mg
야자경화유 127.5 mgPalm kernel oil 127.5 mg
대두인지질 21.0 mgSoybean phospholipids 21.0 mg
젤라틴 211.0 mgGelatin 211.0 mg
글리세린 65.0 mgGlycerin 65.0 mg
디-소르비톨 76.0 mgDi-sorbitol 76.0 mg
파라옥시안식향산메칠 0.56 mgP-hydroxybenzoate 0.56 mg
파라옥시안식향산프로필 0.88 mgP-hydroxybenzoic acid propyl ester 0.88 mg
메칠바닐린 0.56 mg0.56 mg of methyl vanillin
황색 203호 적 량Yellow color 203
<제제실시예 2> 캅셀제의 제조≪ Formulation Example 2 > Preparation of capsule
다음의 원료를 균질하게 혼합하여 1캅셀에 550mg이 함유되도륵 충진한다.The following ingredients are mixed homogeneously and filled in one capsule containing 550 mg.
95% 에탄올 냉침 추출물 125.0 mg95% ethanol cold extract Extract 125.0 mg
오메프라졸 장용과립 170.0 mg (오메프라졸로서 15mg)Omeprazole enteric granules 170.0 mg (15mg as omeprazole)
옥수수전분 170.0 mgCorn starch 170.0 mg
스테아린산마그네슘 2.0 mgMagnesium stearate 2.0 mg
< 제제실시예 3 > 캅셀제의 제조≪ Formulation Example 3 > Preparation of capsule
다음의 원료를 균질하게 혼합하여 1캅셀에 550mg이 함유되도록 충전한다.The following ingredients are mixed homogeneously and filled in one capsule to contain 550 mg.
100% 에탄올 냉침 쑥 추출물 125.0 mg100% Ethanol wormwood extract 125.0 mg
비스무스 섭시트레이트 170.0 mgBismuth subsidence rate 170.0 mg
옥수수전분 83.0 mgCorn starch 83.0 mg
유당 170.0 mgLactose 170.0 mg
스테아린산마그네슘 2.0 mgMagnesium stearate 2.0 mg
< 제제실시예 4 > 정제의 제조≪ Formulation Example 4 > Preparation of tablets
다음의 원료를 균질하게 혼합하여 습식과립법으로 과립화하고 스테아린산마그네슘을 가하여 후혼합한 후 1정이 450mg이 되도록 타정한다.The following ingredients are mixed homogeneously and granulated by a wet granulation method. Magnesium stearate is added to the mixture, which is then mixed to be tableted so that one tablet is 450 mg.
95% 에탄올 냉침 쑥 추출물 125.0 mg95% Ethanol wormwood extract 125.0 mg
라니티딘 50.0 mgRanitidine 50.0 mg
옥수수전분 85.0 mgCorn starch 85.0 mg
유당 170.0 mgLactose 170.0 mg
엘-하이드록시프로필셀룰로오스 12.0 mgEl-hydroxypropylcellulose 12.0 mg
폴리비닐피롤리돈 90 6.0 mgPolyvinylpyrrolidone 90 6.0 mg
에탄올 적 량Ethanol quantity
--------------------------------------------------------------------------------------
스테아린산마그네슘 2.0 mgMagnesium stearate 2.0 mg
본 발명의 의약 조성물은 쑥 추출물 그리고 위염 및 소화성궤양 치료제용 약물로 이루어지며 위염 및 소화성궤양에 대해 치료효과가 뛰어나며, 각각의 약제에 의한 유효성보다 훨씬 우수한 상승적 약효를 나타낸다.The pharmaceutical composition of the present invention is composed of mugwort extract, a drug for treating gastritis and peptic ulcer, and has excellent therapeutic effect on gastritis and peptic ulcer, and exhibits synergistic effect far superior to that of each drug.
또한 쑥 추출물은 궤양치유 과정에 있어 재생점막의 성숙도 및 정상화를 촉진하고 병변부위에 혈관신생을 증가시키는 등 점막보호효과를 나타내어 병변부위의 회복을 도와주므로, 본 발명의 의약 조성물은 H2저해제, 프로톤펌프 저해제에 의한 소화성궤양치료시 문제가 되는 재발율을 억제하며, 치료기간을 단축시킨다. 또한 쑥 추출물은 식용으로도 사용되는 등 부작용이 적으며, H2저해제, 프로톤펌프 저해제, 또는 콜로이드성 비스무스 화합물과 병용시 이들 약제의 복용량을 감소시킴으로써 본 발명의 의약 조성물은 부작용이 감소된 더욱더 안전한 의약 조성물이다.In addition, the mugwort extract promotes the maturation and normalization of the regenerated mucosa in the ulcer healing process and increases mucosal protection such as increasing the angiogenesis in the lesion area, thereby helping the lesion to recover. Thus, the pharmaceutical composition of the present invention can be used as an H 2 inhibitor, It inhibits the recurrence rate, which is a problem in peptic ulcer treatment by proton pump inhibitors, and shortens the treatment period. In addition, the mugwort extract has little side effects such as being used for edible purposes, and by reducing the dose of these drugs when used in combination with an H 2 inhibitor, a proton pump inhibitor, or a colloidal bismuth compound, the pharmaceutical composition of the present invention is more safe Lt; / RTI >
Claims (5)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR1019960045162A KR100404443B1 (en) | 1996-10-10 | 1996-10-10 | Pharmaceutical composition for treating gastritis and peptic ulcer |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR1019960045162A KR100404443B1 (en) | 1996-10-10 | 1996-10-10 | Pharmaceutical composition for treating gastritis and peptic ulcer |
Publications (2)
| Publication Number | Publication Date |
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| KR19980026654A KR19980026654A (en) | 1998-07-15 |
| KR100404443B1 true KR100404443B1 (en) | 2004-04-14 |
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| Application Number | Title | Priority Date | Filing Date |
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| KR1019960045162A KR100404443B1 (en) | 1996-10-10 | 1996-10-10 | Pharmaceutical composition for treating gastritis and peptic ulcer |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR101085970B1 (en) * | 2008-11-25 | 2011-11-22 | 정시남 | Composition for prevention or treatment of gastrointestinal disease containing a coumarin derivative |
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| KR100379189B1 (en) * | 2000-12-14 | 2003-04-08 | 학교법인고려중앙학원 | Agents for gastroenteric disorder by Helicobacter pylori and screening method thereof |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR0127777B1 (en) * | 1994-01-06 | 1998-04-01 | 이은방 | Antigastritic and antiulcer containing eqpatilin |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR0127777B1 (en) * | 1994-01-06 | 1998-04-01 | 이은방 | Antigastritic and antiulcer containing eqpatilin |
Non-Patent Citations (3)
| Title |
|---|
| Korean J. Food Sci. Technol. 이선화 외, 1995, 27(4), p598~604 * |
| 서울여자대학교 박사청구논문, 장혜옥, 1992 * |
| 한국영양학회지, 이지연, 이상선, 1996, 29(6), p608~614 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR101085970B1 (en) * | 2008-11-25 | 2011-11-22 | 정시남 | Composition for prevention or treatment of gastrointestinal disease containing a coumarin derivative |
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| KR19980026654A (en) | 1998-07-15 |
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