KR20040080641A - Composition comprising an extract of Euonymus alatus for prevention and treatment of diabetes - Google Patents
Composition comprising an extract of Euonymus alatus for prevention and treatment of diabetes Download PDFInfo
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- KR20040080641A KR20040080641A KR1020030015509A KR20030015509A KR20040080641A KR 20040080641 A KR20040080641 A KR 20040080641A KR 1020030015509 A KR1020030015509 A KR 1020030015509A KR 20030015509 A KR20030015509 A KR 20030015509A KR 20040080641 A KR20040080641 A KR 20040080641A
- Authority
- KR
- South Korea
- Prior art keywords
- extract
- euonymus
- arrowwood
- polar solvent
- diabetes
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Abstract
Description
본 발명은 혈당강하활성이 있는 화살나무(Euonymus alatus(THUNB.) SIEB.) 조추출물 또는 극성용매 가용추출물을 함유한 당뇨병 예방 및 치료용 조성물에 관한 것이다.The present invention relates to a composition for preventing and treating diabetes containing crude extract of Euonymus alatus (THUNB.) SIEB. Or a polar solvent soluble extract having hypoglycemic activity.
당뇨병(Diabetes)은 인간 및 포유류에서 나타나는 비정상적으로 높은 혈장내의 당(glucose) 수치에 의해 발생하는 질환으로서, 이 비정상적인 당 수치는 혈장내의 헤모글로빈(hemoglobiin)의 수치를 높히게 되며, 만성적인 고혈당증 (hyperglycemia), 아테롬성 동맥경화증(atherosclerosis), 미세혈관병증 (microang iopathy), 신장 질환, 심장 질환, 당뇨병성 망막증(diabetic retinopathy) 및 다른 안과 질환과 같은 일련의 합병증을 야기하게 된다.Diabetes is a disease caused by abnormally high levels of glucose in humans and mammals, which increases the level of hemoglobiin in plasma and chronic hyperglycemia (hyperglycemia). ), A series of complications such as atherosclerosis, microang iopathy, kidney disease, heart disease, diabetic retinopathy and other eye diseases.
진성 당뇨병(Diabetes mellitus)은 두가지 유형으로 특징지워지는데, 인슐린 의존형인 1형 당뇨병(insulin dependent diabetes, IDDM)은 혈액 내의 포도당 조절 호르몬인 인슐린(Insulin)의 분비 결핍으로 야기되며, 주로 10 내지 20대의 젊은연령층에서 발병되기 때문에 소아당뇨병(juvenile diabetes)이라 불리우기도 한다. 2형 당뇨병(non-insulin dependent diabetes, NIDDM)은 주로 40대 이후에 발병되며, 우리나라 당뇨병 환자의 대부분을 차지한다. 제 1형과는 달리 성인형 당뇨병이라 불리우며 발병 원인은 아직 명확히 밝혀져 있지 않으나, 유전적인 요인과 환경적 요소가 함께 관여되어 발생하는 것으로 알려졌다. 제 2형 당뇨병의 병인으로 췌장 베타세포에서 인슐린 분비의 장애와 표적세포에서 인슐린 작용의 결함(인슐린 저항성)이 모두 관찰되는데, 이중 어떠한 변화가 일차적 중요성을 갖는지는 아직 확실하지 않다.Diabetes mellitus is characterized by two types: insulin dependent diabetes (IDDM) is caused by a deficiency of insulin, a glucose-regulating hormone in the blood, mainly in the 10s to 20s. It is called juvenile diabetes because it occurs in younger ages. Type 2 diabetes (non-insulin dependent diabetes, NIDDM) usually occurs after the age of 40, and occupies most of the diabetic patients in Korea. Unlike type 1, it is called adult-type diabetes and the cause of the disease is not clear yet, but it is known that it is caused by genetic factors and environmental factors. The etiology of type 2 diabetes has been observed in both pancreatic beta cells with impaired insulin secretion and defective insulin action (insulin resistance) in target cells, but it is not yet clear which changes are of primary importance.
현재 제 2형 당뇨병 및 인슐린 저항성 같은 합병증에 사용되는 제제로는 5 종류의 화합물군, 즉 비구아니드(biguanides), 티아졸리딘디온 (thiazolidined iones), 설포닐요소(sulfonylureas), 벤조산(benzoic acid) 유도체 화합물 및 α-글루코시다제 저해제(α-glucosidase inhibitor) 등이 사용되고 있으며, 이중 메트포민(metformin)과 같은 비구아니드 화합물은 간에서 당신생 과정 (gluconeogene sis)에 작용을 나타내어 혈당을 조절하는 것으로 알려지고 있는 약물이다. 티아졸리딘디온 화합물은 말초 신경의 포도당 이용율을 증가시키는 작용을 하는 것으로 생각되며, 톨부타미드(tolbutamide) 및 글리부리드(glyburide)와 같은 설포닐요소, 레파글리니드(repaglinide) 화합물과 같은 벤조산 유도체는 인슐린 분비를 자극하여 혈중 포도당를 낮추는 작용을 하는 반면 아카보스(acarbose)와 같은 α-글루코시다제 저해제는 소장에서 탄수화물의 분해를 차단하여 식후 혈당을 조절하는 약물이다.Agents currently used for complications such as type 2 diabetes and insulin resistance include five groups of compounds: biguanides, thiazolidined iones, sulfonylureas, and benzoic acid. Derivative compounds and α-glucosidase inhibitors are used. Among these, biguanide compounds, such as metformin, act on the gluconeogene sis in the liver to regulate blood glucose. It is a known drug. Thiazolidinedione compounds are thought to act to increase glucose utilization in peripheral nerves, benzoic acids such as sulfonylureas, repaglinide compounds such as tolbutamide and glyburide Derivatives stimulate insulin secretion to lower blood glucose, whereas α-glucosidase inhibitors such as acarbose are drugs that control post-prandial blood sugar by blocking the breakdown of carbohydrates in the small intestine.
상기의 설포닐요소 화합물은 인슐린 의존형인 제 1형 당뇨병 환자에게는 투여할 수 없으며, 비인슐린 의존형인 제 2형 당뇨병 환자는 인슐린 분비를 감소하게 되고, 여성 환자에게 비정상적인 태아 출생, 유산(abortion) 및 사산(stillbirth)과 같은 부작용을 야기할 수 있다. 추가적으로, 대부분의 설포닐요소 화합물은 설포닐요소의 대사작용으로 인해 간 및 신장 기능에 장애가 있는 환자에게는 조심스럽게 투여해야 한다.The sulfonylurea compound may not be administered to insulin-dependent type 1 diabetic patients, and non-insulin-dependent type 2 diabetic patients may decrease insulin secretion and abnormal fetal birth, abortion, and May cause side effects such as stillbirth. In addition, most sulfonylurea compounds should be administered carefully to patients with impaired liver and kidney function due to the metabolism of sulfonylurea.
메트포민과 같은 비구아니드 함유 제제의 메카니즘은 확실하게 규명되지는 않았으나, 비구아니드 화합물은 췌장의 인슐린 분비를 증가시킬 수 없음에도 불구하고 설포닐요소보다 더 효과적으로 혈당을 강하하고 저혈당 유발의 빈도도 낮다. 그러나 투여 초기에 구역질, 구토, 설사 및 발진 등을 야기할 수 있으며, 치명적인 유산혈증(lactic acidosis)과 같은 부작용을 야기할 수 있으므로, 미국내에서는 임상실험용 시약으로만 사용가능하다.Although the mechanism of biguanide-containing preparations such as metformin has not been elucidated, although biguanide compounds are unable to increase pancreatic insulin secretion, they lower blood sugar levels more effectively than sulfonylurea and also induce hypoglycemia. low. However, it can cause nausea, vomiting, diarrhea and rash at the beginning of administration, and can cause side effects such as fatal lactic acidosis, so it can only be used as a clinical reagent in the United States.
설포닐요소 및 비구아니드 함유 제제들은 상기와 같은 결점 및 부작용을 가지고 있으므로, 낮은 부작용 및 높은 안전성을 갖는 탁월한 혈당강하제가 필요한 실정이다.Since sulfonylurea and biguanide-containing preparations have the above disadvantages and side effects, there is a need for an excellent hypoglycemic agent having low side effects and high safety.
본 발명에 사용된 화살나무(참빗나무,Euonymus alatus(THUNB.) SIEB.)는 무환자나무목 노박덩굴과의 낙엽관목으로, 한국, 일본, 사할린, 중국 지역에 분포한다. 어린잎은 나물로 하고 가지의 날개를 귀전우(鬼剪羽)라고 한다. 잎에는 에피프리에델라놀(epifriedelanol), 프리에델린(friedelin), 퀘르세틴(quercetin), 둘시톨(dulcitol)이 함유되어있다. 종자유에는 포화지방산(20%), 올레인산, 리놀산,리놀렌산, 카프릭산 및 안식향산 등이 함유되어 있다. 한방에서는 지혈, 구어혈, 통경에 사용한다. Arrowwood used in the present invention (Truewood, Euonymus alatus (THUNB.) SIEB.) Is a deciduous shrub with a lone tree, Novak, and is distributed in Korea, Japan, Sakhalin and China. Young leaves are herbs and the wings of branches are called earheads. The leaves contain epipriedelanol, priedelin, quercetin and dulcitol. Seed oil contains saturated fatty acids (20%), oleic acid, linoleic acid, linolenic acid, capric acid and benzoic acid. Oriental medicine is used for hemostasis, gore blood, pain.
이에 본 연구자는 부작용이 없으며 안전한 천연 제제를 이용한 당뇨병 질환 치료제를 개발하기 위하여 화살나무 극성용매 가용추출물을 분리하여 내당능시험 (oral glucose tolerance test, OGTT)과 스트렙토조토신 유발 당뇨 흰쥐에서 항당뇨활성이 있음을 확인하였고, 혈당 및 뇨당을 감소시킴을 확인하여, 당뇨 질환에 탁월한 치료 및 예방 효능이 있음을 확인하여 본 발명을 완성하였다.In this regard, the present inventors have no side effects and anti-diabetic activity in oral glucose tolerance test (OGTT) and streptozotocin-induced diabetic rats was isolated by extracting the polar solvent-soluble extracts from arrowwood to develop a safe natural drug for diabetic disease It was confirmed that the reduction in blood sugar and urine glucose, and confirmed that the excellent therapeutic and prophylactic efficacy for diabetes diseases to complete the present invention.
본 발명의 목적은 화살나무의 추출물을 함유하는 당뇨병 질환의 예방 및 치료에 효과적인 약학조성물 및 건강 기능 식품을 제공하는 것이다.It is an object of the present invention to provide a pharmaceutical composition and a dietary supplement that is effective for the prevention and treatment of diabetes diseases containing the extract of arrowwood.
도 1 은 ICR 마우스에 화살나무의 에탄올 추출물을 용량별로 경구투여하였을 때, 혈당에 미치는 효과를 나타낸 도이고,1 is a diagram showing the effect on blood glucose when oral administration of the ethanol extract of arrowwood to ICR mice by dose,
도 2 는 상기 도 1에서 0분부터 90분까지의 용량별 각 포도당 반응 곡선하 면적을 나타낸 도이고,Figure 2 is a diagram showing the area under each glucose response curve for each dose from 0 minutes to 90 minutes in Figure 1,
도 3 은 화살나무 추출물의 에탄올 추출물, 물분획물 및 에테르 분획물을 경구투여하였을 때, 혈당에 미치는 효과를 나타낸 도이고,3 is a diagram showing the effect on blood glucose when oral administration of ethanol extract, water fraction and ether fraction of arrowwood extract,
도 4 는 상기 도 3에서 0분부터 90분까지의 시료당 포도당 반응 곡선하 면적을 나타낸 도이고,Figure 4 is a diagram showing the area under the glucose response curve per sample from 0 to 90 minutes in Figure 3,
도 5 는 화살나무 추출물의 물분획물을 용량별로 경구투여하였을 때, 혈당에 미치는 효과를 나타낸 도이고,5 is a diagram showing the effect on blood glucose when orally administered water fractions of the arrowwood extract,
도 6 은 상기 도 5에서 0분부터 90분까지의 용량별 각 포도당 반응 곡선하 면적을 나타낸 도이고,Figure 6 is a diagram showing the area under each glucose response curve for each dose from 0 minutes to 90 minutes in Figure 5,
도 7 은 스트렙토조토신-유도 당뇨병 흰쥐에서의 화살나무 추출물이 체중에 미치는 효과를 나타낸 도이고,7 is a diagram showing the effect of arrowwood extract on body weight in streptozotocin-induced diabetic rats,
도 8 은 스트렙토조토신-유도 당뇨병 흰쥐에서의 화살나무 추출물이 혈당에 미치는 효과를 나타낸 도이다.8 is a diagram showing the effect of arrowwood extract on blood glucose in streptozotocin-induced diabetic rats.
상기 목적을 달성하기 위하여, 본 발명은 혈당저하 활성이 있는 화살나무의 조추출물 또는 극성용매가용추출물을 함유하는 당뇨병 및 당뇨성질환 예방 및 치료용 조성물을 제공한다.In order to achieve the above object, the present invention provides a composition for preventing and treating diabetes mellitus and diabetic disease containing crude extract or polar solvent soluble extract of arrowwood with hypoglycemic activity.
상기 화살나무 조추출물은 물, 메탄올, 에탄올 등과 같은 극성용매 및 이들의 혼합용매, 바람직하게는 70% 에탄올혼합용매에 가용한 추출물이 바람직하다.The crude extract of arrowwood is preferably an extract available in a polar solvent such as water, methanol, ethanol and the like, and a mixed solvent thereof, preferably a 70% ethanol mixed solvent.
또한, 상기 화살나무의 극성용매가용추출물은 상기 조추출물로부터 비극성용매가용부를 제거하고 남은 물, 메탄올, 에탄올 등과 같은 극성용매 및 이들의 혼합용매, 바람직하게는 물에 가용한 추출물을 포함한다.In addition, the polar solvent soluble extract of the arrowwood includes a polar solvent such as water, methanol, ethanol and the like remaining after removing the non-polar solvent soluble portion from the crude extract and a mixture thereof, preferably an extract available in water.
상기 비극성용매 가용부는 에틸아세테이트, 클로로포름, 헥산, 에테르 등과 같은 비극성용매, 또는 이들의 혼합용매, 바람직하게는 에테르 용매에 가용한 추출물을 포함한다.The nonpolar solvent soluble part includes an extract which is soluble in a nonpolar solvent such as ethyl acetate, chloroform, hexane, ether, or a mixed solvent thereof, preferably an ether solvent.
상기 화살나무는 참빗나무(Euonymus alatus(THUNB.) SIEB.), 좀참빗살나무 (Euonymus bungeanusMAXIM.), 참빗살나무(E. sieboldianusBLUME) 등의 식물을 포함한다.The sapling tree includes plants such as Euonymus alatus (THUNB.) SIEB., Euonymus bungeanus MAXIM., And E. sieboldianus BLUME.
상기 화살나무의 조추출물 및 극성용매 가용 추출물을 분리하는 방법은 하기와 같다.The method of separating the crude extract and the polar solvent soluble extract of the arrowwood is as follows.
이하, 본 발명을 더욱 상세히 설명한다.Hereinafter, the present invention will be described in more detail.
본 발명의 화살나무의 조추출물은,The crude extract of the arrow tree of the present invention,
건조하여 파쇄한 화살나무 무게(㎏)의 약 1 내지 20배의 부피, 바람직하게는 5 내지 10배의 물, 메탄올, 에탄올과 같은 극성용매 또는 이들의 혼합용매를 가한 후, 20 내지 100℃, 바람직하게는 40 내지 60℃, 약 1시간 내지 3일, 바람직하게는 1시간 내지 1일동안, 1회 내지 5회 열수추출, 초음파 추출, 환류냉각추출 등의 추출방법에 의하여 추출 후 여과하고 감압건조 또는 동결건조하여, 본 발명의 화살나무 조추출물을 수득할 수 있다.About 1 to 20 times the volume of the dried and crushed arrowwood (kg), preferably 5 to 10 times water, a polar solvent such as methanol or ethanol or a mixed solvent thereof, and then 20 to 100 ° C., Preferably 40 to 60 ℃, about 1 hour to 3 days, preferably for 1 hour to 1 day, filtered by extraction method such as hot water extraction, ultrasonic extraction, reflux cooling extraction once or five times and reduced pressure By drying or lyophilization, the arrowwood crude extract of the present invention can be obtained.
또한, 본 발명의 화살나무 극성용매 가용추출물은, 상기의 조추출물을 물, 메탄올, 에탄올과 같은 극성용매 또는 이들의 혼합용매에 용해시켜, 동량의 에테르, 에틸아세테이트, 클로로포름, 헥산과 같은 비극성용매를 가한 후, 1시간 내지48시간동안 분획을 하여 극성용매가용층 및 비극성용매가용층을 각각 수득하여 감압건조후 동결건조하여 수득될 수 있다.In addition, the arrowwood polar solvent soluble extract of the present invention, the crude extract is dissolved in a polar solvent such as water, methanol, ethanol or a mixed solvent thereof, the same amount of non-polar solvent such as ether, ethyl acetate, chloroform, hexane After the addition, the mixture was fractionated for 1 hour to 48 hours to obtain a polar solvent soluble layer and a non-polar solvent soluble layer, respectively.
상기 분리된 화살나무 극성용매가용추출물을 가지고 내당능시험 (oral glucose tolerance test, OGTT)과 스트렙토조토신 유발 당뇨 흰쥐에서의 시험에서 항당뇨활성이 있음을 확인하였고, 혈당 및 뇨당을 감소시켜 당뇨 질환에 탁월한 치료 및 예방 효능이 있음을 알 수 있었다.It was confirmed that the anti-diabetic activity was tested in the glucose tolerance test (OGTT) and streptozotocin-induced diabetic rats with the isolated polar solvent-soluble extract of arrowwood, and reduced the blood sugar and urine glucose to diabetic disease It was found to have excellent therapeutic and prophylactic effects.
본 발명은 상기 제법으로 제조된 화살나무의 극성용매 가용추출물을 유효성분으로 함유하는 혈당강하용 조성물을 제공한다.The present invention provides a blood glucose lowering composition containing the polar solvent soluble extract of arrowwood prepared by the above method as an active ingredient.
본 발명은 상기 제법으로 제조된 화살나무 극성용매 가용추출물을 유효성분으로 함유하는 당뇨병 및 당뇨성 질환 예방 및 치료용 약학 조성물을 제공한다.The present invention provides a pharmaceutical composition for the prevention and treatment of diabetes mellitus and diabetic disease containing the arrowwood polar solvent soluble extract prepared by the above method as an active ingredient.
추가적으로, 본 발명의 화살나무 극성용매 가용추출물을 함유하는 혈당강하용 조성물, 당뇨병 및 당뇨성 질환 예방 및 치료용 약학조성물은, 조성물 총 중량에 대하여 상기 추출물을 0.1 내지 50 중량 %로 포함한다.In addition, the composition for lowering blood glucose, the pharmaceutical composition for preventing and treating diabetes mellitus and diabetic diseases, containing the arrow-tree polar solvent soluble extract of the present invention comprises 0.1 to 50% by weight of the extract based on the total weight of the composition.
특히 상기 당뇨성 질환은 당뇨병이 만성적으로 진행되면서 당뇨병으로부터 유발되는 퇴행성 합병증인 당뇨성 망막증, 당뇨성 신경증, 신장병, 죽상 동맥경화증, 심근 장해, 피부 장해, 당뇨성 발 증후군 및 말초혈관 질병 등의 합병증도 포함된다.In particular, the diabetic diseases are complications such as diabetic retinopathy, diabetic neuropathy, nephropathy, atherosclerosis, myocardial disorders, skin disorders, diabetic foot syndrome, and peripheral vascular diseases as diabetes progresses chronically. Also included.
본 발명의 화살나무 극성용매가용추출물을 포함하는 조성물은 약학적 조성물의 제조에 통상적으로 사용하는 적절한 담체, 부형제 및 희석제를 더 포함할 수 있다.The composition comprising the arrowwood polar solvent soluble extract of the present invention may further comprise suitable carriers, excipients and diluents commonly used in the manufacture of pharmaceutical compositions.
본 발명의 극성용매가용추출물을 포함하는 조성물에 포함될 수 있는 담체, 부형제 및 희석제로는, 락토즈, 덱스트로즈, 수크로스, 솔비톨, 만니톨, 자일리톨, 에리스리톨, 말티톨, 전분, 아카시아 고무, 알지네이트, 젤라틴, 칼슘 포스페이트, 칼슘 실리케이트, 셀룰로즈, 메틸 셀룰로즈, 미정질 셀룰로스, 폴리비닐 피롤리돈, 물, 메틸히드록시벤조에이트, 프로필히드록시벤조에이트, 탈크, 마그네슘 스테아레이트 및 광물유를 들 수 있다.Carriers, excipients and diluents that may be included in the composition comprising the polar solvent soluble extract of the present invention include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, Gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil.
본 발명에 따른 추출물을 포함하는 조성물은, 각각 통상의 방법에 따라 산제, 과립제, 정제, 캡슐제, 현탁액, 에멀젼, 시럽, 에어로졸 등의 경구형 제형, 외용제, 좌제 및 멸균 주사용액의 형태로 제형화하여 사용될 수 있다.Compositions comprising extracts according to the invention are formulated in the form of powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols and the like, oral preparations, suppositories and sterile injectable solutions, respectively, according to conventional methods. Can be used.
본 발명의 추출물의 사용량은 환자의 나이, 성별, 체중에 따라 달라질 수 있으나, 일반적으로 0.01 내지 500mg/㎏의 양, 바람직하게는 0.1 내지 100mg/㎏의 양을 일일 1회 내지 수회로 나누어 투여할 수 있다. 또한 그 추출물의 투여량은 투여경로, 질병의 정도, 성별, 체중, 나이 등에 따라서 증감될 수 있다. 따라서, 상기 투여량은 어떠한 면으로든 본 발명의 범위를 한정하는 것은 아니다.The amount of the extract of the present invention may vary depending on the age, sex, and weight of the patient, but in general, an amount of 0.01 to 500 mg / kg, preferably 0.1 to 100 mg / kg, may be administered once or several times a day. Can be. In addition, the dosage of the extract can be increased or decreased depending on the route of administration, the degree of disease, sex, weight, age and the like. Therefore, the above dosage does not limit the scope of the present invention in any aspect.
본 발명의 약학 조성물은 쥐, 생쥐, 가축, 인간 등의 포유동물에 다양한 경로로 투여될 수 있다. 투여의 모든 방식은 예상될 수 있는데, 예를 들면, 경구, 직장 또는 정맥, 근육, 피하, 자궁내 경막 또는 뇌혈관내 (intracerebroventricular) 주사에 의해 투여될 수 있다.The pharmaceutical composition of the present invention can be administered to mammals such as rats, mice, livestock, humans by various routes. All modes of administration can be expected, for example by oral, rectal or intravenous, intramuscular, subcutaneous, intrauterine dural or intracerebroventricular injection.
또한 본 발명의 화살나무 극성용매 가용추출물은 기타 식품의 주, 부원료 및 식품첨가제로서 사용이 가능하다.In addition, the arrowwood polar solvent soluble extract of the present invention can be used as a main, secondary raw material and food additive of other foods.
또한 본 발명은 화살나무 극성용매 가용추출물 및 식품학적으로 허용 가능한 식품 보조 첨가제를 포함하는 혈당 강하 및 당뇨병 예방을 위한 건강기능식품을 제공한다.In another aspect, the present invention provides a health functional food for the prevention of blood sugar lowering and diabetes, including the arrow-tree polar solvent soluble extract and a food supplement acceptable food supplement.
본 발명의 추출물을 포함하는 조성물은 당뇨병 예방 및 치료를 위한 약제, 식품 및 음료 등에 다양하게 이용될 수 있다. 본 추출물을 첨가할 수 있는 식품으로는, 예를 들어, 각종 식품류, 음료, 껌, 차, 비타민 복합제, 건강기능식품류 등이 있다.The composition comprising the extract of the present invention may be used in various ways, such as drugs, food and beverages for the prevention and treatment of diabetes. Examples of the food to which the present extract can be added include various foods, beverages, gums, teas, vitamin complexes, and health functional foods.
본 발명의 추출물 자체는 독성 및 부작용은 거의 없으므로 예방 목적으로 장기간 복용시에도 안심하고 사용할 수 있는 약제이다.Extract itself of the present invention is a drug that can be used with confidence even for long-term administration for the purpose of prevention because there is little toxicity and side effects.
본 발명의 상기 추출물은 당뇨병의 예방을 목적으로 식품 또는 음료에 첨가될 수 있다.The extract of the present invention may be added to food or beverage for the purpose of preventing diabetes.
본 발명의 건강 음료 조성물은 필수 성분으로서 상기 추출물을 함유하는 외에는 액체성분에는 특별한 제한점은 없으며, 통상의 음료와 같이 여러가지 향미제 또는 천연 탄수화물 등을 추가 성분으로서 함유할 수 있다. 상술한 천연 탄수화물의 예는 모노사카라이드, 예를 들어, 포도당, 과당 등; 디사카라이드, 예를 들어 말토스, 슈크로스 등; 및 폴리사카라이드, 예를 들어 덱스트린, 시클로덱스트린 등과 같은 통상적인 당, 및 자일리톨, 소르비톨, 에리트리톨 등의 당알콜이다. 상술한 것 이외의 향미제로서 천연 향미제(타우마틴, 스테비아 추출물(예를 들어 레바우디오시드 A, 글리시르히진등) 및 합성 향미제(사카린, 아스파르탐 등)를 유리하게 사용할 수 있다. 상기 천연 탄수화물의 비율은 본 발명의 조성물 100 ㎖당 일반적으로 약 1 내지 20 g, 바람직하게는 약 5 내지 12 g이다.The health beverage composition of the present invention is not particularly limited in the liquid component except for containing the extract as an essential ingredient, and may contain various flavors or natural carbohydrates, etc., as additional ingredients, as in ordinary beverages. Examples of the above-mentioned natural carbohydrates include monosaccharides such as glucose, fructose and the like; Disaccharides such as maltose, sucrose and the like; And conventional sugars such as polysaccharides such as dextrin, cyclodextrin, and sugar alcohols such as xylitol, sorbitol, and erythritol. As flavoring agents other than those mentioned above, natural flavoring agents (tauumatin, stevia extract (for example, rebaudioside A, glycyrrhizin, etc.) and synthetic flavoring agents (saccharin, aspartame, etc.) can be advantageously used. The proportion of said natural carbohydrates is generally about 1-20 g, preferably about 5-12 g per 100 ml of the composition of the present invention.
상기 외에 본 발명의 조성물은 여러가지 영양제, 비타민, 광물(전해질), 합성 풍미제 및 천연 풍미제 등의 풍미제, 착색제 및 중진제(치즈, 초콜릿 등), 펙트산 및 그의 염, 알긴산 및 그의 염, 유기산, 보호성 콜로이드 증점제, pH 조절제, 안정화제, 방부제, 글리세린, 알콜, 탄산 음료에 사용되는 탄산화제 등을 함유할 수 있다. 그밖에 본 발명의 조성물들은 천연 과일 쥬스 및 과일 쥬스 음료 및 야채 음료의 제조를 위한 과육을 함유할 수 있다. 이러한 성분은 독립적으로 또는 조합하여 사용할 수 있다. 이러한 첨가제의 비율은 그렇게 중요하진 않지만 본 발명의 조성물 100 중량부 당 0 내지 약 20 중량부의 범위에서 선택되는 것이 일반적이다.In addition to the above, the composition of the present invention includes various nutrients, vitamins, minerals (electrolytes), flavors such as synthetic flavors and natural flavors, coloring and neutralizing agents (such as cheese and chocolate), pectic acid and salts thereof, alginic acid and salts thereof. , Organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohols, carbonation agents used in carbonated beverages, and the like. The compositions of the present invention may also contain pulp for the production of natural fruit juices and fruit juice beverages and vegetable beverages. These components can be used independently or in combination. The proportion of such additives is not so critical but is generally selected from the range of 0 to about 20 parts by weight per 100 parts by weight of the composition of the present invention.
본 발명은 다음의 실시예에 의거하여 더욱 상세히 설명되나, 본 발명이 이에 의해 제한되지는 않는다.The present invention is described in more detail based on the following examples, although the present invention is not limited thereto.
참고예. 통계 처리Reference example. Statistical processing
모든 실험의 결과들은 평균 ±표준편차로 나타내었고 통계 처리는 스튜던트 티-테스트(Student t-test)를 실시하여 p<0.05를 기준으로 유의성 여부를 판정하였다(*은 P<0.05, **는 P<0.01, ***는 P<0.001 로 대조군과 유의적으로 다름을 의미함).The results of all experiments were expressed as mean ± standard deviation and statistical processing was performed by Student's t-test to determine the significance based on p <0.05 (* is P <0.05, ** is P <0.01, *** means P <0.001, which is significantly different from the control).
실시예 1. 화살나무 조추출물 제조Example 1 Preparation of Arrowwood Crude Extract
화살나무 샘플을 한국 토종약초연구소에서 공급 받아 사용하였다. 음건하여잘 말린 화살나무 가루 400 g을 70% 에탄올 3L로 4시간씩 2회에 걸쳐 냉각기가 달린 수욕상에서 추출한 후, 추출액을 여과지(Whatman type 2)로 여과하고, 감압 건조한 후 동결건조하여 18g의 분말의 수득하였으며, 이를 하기 실험에 사용하였다.Arrowwood samples were supplied from the Korean Institute of Herbal Medicine. After extracting 400 g of dried and dried arrowwood powder with 3L of 70% ethanol twice over 4 hours in a water bath with a cooler, the extract was filtered through a filter paper (Whatman type 2), dried under reduced pressure, and lyophilized to dryness. A powder was obtained, which was used for the following experiment.
실시예 2. 화살나무 극성용매 가용추출물(2-1) 제조Example 2. Preparation of arrowwood polar solvent soluble extract (2-1)
상기 에탄올 추출물 18 g을 동량의 물과 에테르에 용해시킨 후 12시간 분획여두에 방치하여 얻은 물 분획과 에테르 분획을 동결 건조하여 각각을 물분획물(2-1) 12.8 g(처음 사용한 화살나무 400 g의 6.4%), 에테르분획물 (2-2) 4 g(처음 사용한 화살나무 400 g의 2%) 얻었다. 모든 시료는 4℃에 보관하였으며 실험시 증류수에 녹여 바로 실험에 사용하였다.After dissolving 18 g of the ethanol extract in the same amount of water and ether, the mixture was freeze-dried from the water fraction and the ether fraction obtained by standing in a fractional filter for 12 hours, respectively, 12.8 g of the water fraction (2-1) (400 g of the first arrow tree). 6.4%), ether fraction (2-2) was obtained 4g (2% of the 400 g of the first arrow). All samples were stored at 4 ℃ and dissolved in distilled water at the time of experiment immediately used in the experiment.
실험예 1. 화살나무 추출물의 경구 내당능 시험(Oral Glucose Tolerance Test, OGTT)Experimental Example 1. Oral Glucose Tolerance Test (OGTT) of Arrow Extract
1-1. 실험동물1-1. Laboratory animals
5주령의 ICR 마우스를 구입(대한바이오링크, 충북음성)하여 본 실험실에서 1주일간 적응시킨 후 1차 증류수에 녹인 시료를 각각 경구 투여하였다. 실험동물은 습도 50%, 온도 24~26℃로 유지되는 동물 사육장에서 사육하였으며 물은 자유롭게 섭취할 수 있도록 공급하였다.Five-week-old ICR mice were purchased (Dae Biolink, Chungbuk Negative), and were acclimated for one week in the laboratory, and then orally administered samples dissolved in primary distilled water. The experimental animals were bred in animal kennels maintained at a humidity of 50% and a temperature of 24 ~ 26 ℃, and water was supplied for free intake.
실험 전 실험동물은 12~13시간동안 절식시킨 후, 안와 채혈하여 얻어진 혈액으로부터 혈중의 포도당 농도를 측정한 후, 각 동물군을 10마리씩 대조군, 양성 대조 약물군, 시료 투여군으로 나누었다.Before the experiment, the animals were fasted for 12 to 13 hours, the blood glucose levels were measured from the blood obtained by orbital blood collection, and each animal group was divided into a control group, a positive control drug group, and a sample administration group.
1-2. 경구 내당능시험1-2. Oral glucose tolerance test
실험 시작 30분 전에 준비된 실시예 1 및 2의 화살나무 시료를 500 mg/kg, 1000 mg/kg, 2000 mg/kg의 농도로 경구 투여한 후, 0분의 시점에서 각 군마다 포도당(1.5 g/kg, Sigma사)을 투여하고 투여와 동시인 0분에서 안와채혈을 하고 계속해서 30분, 60분, 90분에 안와채혈을 하여 혈당을 측정해 봄으로써 혈당변화를 관찰하였다. 실험동물의 안와정맥으로부터 헤파린(heparin)이 처리된 모세관을 사용하여 혈액을 채취하였다. 채취한 혈액은 5000 rpm, 4℃에서 5분간 원심 분리(Microcentrifuge 5417R, Eppendorf사, Germany)하여 실험에 사용하였다. 혈중 포도당은 글루코스 옥시다제 방법(glucose oxidase method, Trinder, Sigma Diagnostic, St.Louis, MO) (Kakkar R. et al.;Life Sci.,60(9), pp667-679, 1997)에 의해 측정하였다.Samples of arrowwood samples of Examples 1 and 2 prepared 30 minutes before the start of the experiment were orally administered at concentrations of 500 mg / kg, 1000 mg / kg, and 2000 mg / kg, followed by glucose (1.5 g) in each group at the time point of 0 minutes. / kg, Sigma) and the orbital blood collection at 0 minutes concurrent with the administration and the orbital blood collection at 30 minutes, 60 minutes, and 90 minutes to measure the blood glucose changes were observed. Blood was collected from heparin-treated capillaries from orbital veins of experimental animals. The collected blood was centrifuged at 5000 rpm and 4 ° C. for 5 minutes (Microcentrifuge 5417R, Eppendorf, Germany) and used for the experiment. Blood glucose was measured by the glucose oxidase method (Trinder, Sigma Diagnostic, St. Louis, MO) (Kakkar R. et al . ; Life Sci. , 60 (9) , pp667-679, 1997). .
도 1과 도 2는 화살나무의 70% 에탄올 추출물을 500 mg/kg, 1000 mg/kg, 2000 mg/kg의 농도로 하여 용량 의존적 경향을 나타내는지 알아보기 위하여 시행한 실험결과로, OGTT 실험 결과에 의해 얻어진 혈당 변화와 곡선하 면적을 나타낸 것이다. 1000 mg/kg과 2000 mg/kg의 농도에서 유의성이 나타남을 볼 수 있다. 각 농도의 시료 투여 후 곡선하 면적의 감소가 각각 6.5%, 19.8%, 19.3%를 나타내었고, 용량의존적인 혈당강하활성을 보여주었으나, 1000 mg/kg과 2000 mg/kg 농도간에 큰 차이는 나타나지 않았다.1 and 2 are experimental results conducted to determine whether the 70% ethanol extract of arrowwood shows a dose-dependent tendency with the concentration of 500 mg / kg, 1000 mg / kg, 2000 mg / kg, OGTT test results Shows the change in blood sugar and the area under the curve. It can be seen that the significance is shown at the concentration of 1000 mg / kg and 2000 mg / kg. The decrease in the area under the curve was 6.5%, 19.8%, and 19.3% after the administration of the sample at each concentration, and dose-dependent hypoglycemic activity was shown, but there was a big difference between 1000 mg / kg and 2000 mg / kg concentrations. Did not appear.
도 3과 도 4는 화살나무를 에테르와 물층으로 분획하여 얻어진 화살나무 분획물을 가지고 분획된 양(물 700 mg/kg, 에테르 300 mg/kg)을 고려하여 그 농도에 맞게 OGTT를 시행한 결과에 의해 얻어진 혈당 변화 및 곡선하 면적을 나타낸 것이다. 그림에서 보는 바와 같이 물층 700 mg/kg 용량은 70% 에탄올 1 g/kg 용량을 투여한 그룹과 비교시 거의 같은 혈당강하 활성을 나타내어, 대부분의 혈당강하 활성 성분은 물층으로 이송됨을 알 수 있었다. 따라서 이후 실험에서는 물 층을 이용하여 용량의존적인 실험을 진행하였다.3 and 4 are the results of the OGTT according to the concentration in consideration of the fraction (700 mg / kg water, 300 mg / kg ether) fraction with the arrowwood fraction obtained by dividing the arrowwood into ether and water layer. The change in blood glucose and the area under the curve are shown. As shown in the figure, the 700 mg / kg water layer showed almost the same hypoglycemic activity as compared to the group administered 1 g / kg of 70% ethanol, indicating that most of the hypoglycemic active ingredients were transferred to the water layer. Therefore, in subsequent experiments, a dose-dependent experiment was conducted using the water layer.
도 5와 도 6은 활성 분획물을 함유하는 화살나무의 물층을 250 mg/kg, 500 mg/kg, 700 mg/kg의 농도로 나누어 OGTT를 시행한 결과에 의해 얻어진 혈당 변화와 곡선하 면적을 나타낸 것이다. 양성대조 약물로 글리메피리드(glimepiride)를 사용하였다. 그림 6에서 보듯이 용량의존적으로 화살나무 극성용매 가용추출물이 혈당상승을 억제함을 알 수 있었다.5 and 6 show the blood glucose change and the area under the curve obtained by OGTT by dividing the water layer of the arrowwood containing the active fraction into concentrations of 250 mg / kg, 500 mg / kg and 700 mg / kg. will be. Glimepiride was used as a positive control drug. As shown in Figure 6, the dose-dependent polar solvent soluble extract suppressed the blood glucose increase.
하기의 표 1은 OGTT 실험에서 0분과 30분의 혈장내 인슐린 농도를 나타낸 것이다. 500 mg/kg과 700 mg/kg의 화살나무를 투여한 군은 대조군에 비해 인슐린 수치가 0분에서 각각 1.2배 및 1.6배, 30분에서 1.2배 및 1.3배 가량 상승되어 나타났으며 700mg/kg의 화살나무를 투여한 군과 양성대조약물인 글리메피리드 (glimepiride)를 투여한 군에서 인슐린치가 유의적으로 상승됨을 볼 수 있었다.Table 1 below shows the plasma insulin concentration at 0 and 30 minutes in the OGTT experiment. In the group administered 500 mg / kg and 700 mg / kg arrowwood, insulin levels were increased 1.2 times and 1.6 times at 0 minutes and 1.2 times and 1.3 times at 30 minutes, respectively, compared to the control group. Insulin levels were significantly increased in the group administered with the arrow tree and the group administered the glimepiride, a positive control drug.
실험예 2. 다중 저용량 스트렙토조토신-유도 당뇨병 랫트(Multiple Low Dose Streptozotocin-induced Diabetic Rat)에서 화살나무 활성 분획물의 항당뇨 활성 검색Experimental Example 2. Screening of antidiabetic activity of arrowwood active fractions in Multiple Low Dose Streptozotocin-induced Diabetic Rats
2-1. 실험동물2-1. Laboratory animals
150-160 g 무게의 수컷 스프라그-도올리 랫트(Spraque-Dawley rat)를 대한바이오링크로부터 구입하여 본 실험실에서 1 주일간 적응시킨 후 1차 증류수에 녹인 실시예 시료를 각각 경구 투여하였다. 실험 동물은 습도 50%, 온도 24~26℃로 유지되는 동물 사육장에서 사육하였으며 물은 자유롭게 섭취할 수 있도록 공급하였다. 무작위적으로 SD 랫트를 나누어 정상대조군(normal control, NC), 당뇨성 대조군(diabetic control, DC), 동시 처리군(co-treatment group, CO) 와 후처리군(post-treatment group, POST)으로 분리하였다.Male Spraque-Dawley rats weighing 150-160 g were purchased from Daehan Biolink and adapted for 1 week in the laboratory, followed by oral administration of sample samples dissolved in primary distilled water. Experimental animals were bred in animal kennels maintained at a humidity of 50% and a temperature of 24 ~ 26 ℃, and water was supplied for free intake. Randomly divided SD rats were divided into normal control (NC), diabetic control (DC), co-treatment group (CO) and post-treatment group (POST). Separated.
2-2. 식이 및 음수 섭취 변화 측정2-2. Measure changes in dietary and negative intake
각 실험군은 5일간 100 mM 구연산완충액(citrate buffer)에 25 mg/kg의 농도로 스트렙토조토신(streptozotocin)을 녹여 복강 투여하였다. 구연산 완충액을 투여받은 랫트를 대조군으로 하였으며 후처리군은 당뇨가 유도된 (혈당치가 240 mg/㎗ 이상) 시점부터 투여를 시작하였다. 본 실험에서는 300 mg/kg의 농도의 화살나무가 복강투여 되었다. 혈당과 체중은 5일마다 6시간의 절식 후에 측정하였으며 시료의 투여를 마친 시점에서 식이 및 음수량을 측정하였다.Each experimental group was intraperitoneally administered with streptozotocin (streptozotocin) at a concentration of 25 mg / kg in 100 mM citric acid buffer (citrate buffer) for 5 days. Rats receiving citric acid buffer were used as a control group, and the post-treatment group started administration from the time when diabetes was induced (blood glucose level of 240 mg / dL or more). In this experiment, 300 mg / kg arrowhead was intraperitoneally administered. Blood glucose and body weight were measured after 6 hours of fasting every 5 days, and diet and drinking volume were measured at the end of the administration of the sample.
하기 표 2는 실험이 진행된 3주 후에 얻어진 식이 및 음수량의 변화를 나타낸 것이다. 정상 대조군은 실험이 진행되는 동안 큰 변화를 나태내지 않은 반면, 당뇨 대조군은 유의적으로 식이 및 음수량의 섭취가 상승됨을 나타냈다. 동시 처리군과 후처리군의 경우 당뇨 대조군에 비해 식이 및 음수량의 섭취가 감소되어 있음을 볼 수 있었다.Table 2 below shows the changes in dietary and negative amounts obtained after 3 weeks of the experiment. The normal control group did not show significant changes during the experiment, whereas the diabetic control group showed a significant increase in dietary and negative intake. In the simultaneous treatment group and the post-treatment group, the intake of dietary and drinking water was reduced compared to the diabetic control group.
2-3. 체중 및 혈당 변화 측정2-3. Body weight and blood sugar change measurement
도 7은 체중 변화를 나타낸 것이다. 스트렙토조토신(25 mg/kg)을 투여한 실험동물군은 투여하지 않은 동물군에 비해 체중이 늘지 않고 오히려 약간 감소하는 경향을 나타내었다. 실험 진행 후 15일 되는 시점에서 당뇨 대조군과 처리군간에 큰 차이는 보이지 않았지만 동시 처리군과 후처리군의 경우 체중이 약간 상승함을 나타냈다. 도 8는 혈중 포도당의 변화를 나타낸 것이다. 실험이 진행되는 동안 당뇨 대조군의 혈당은 다른 군에 비해 높은 수치를 유지하였고 동시 처리군의 경우 시료 투여 시점 3주 후부터는 혈당이 상승을 억제하는 것으로 나타났다. 20일째에 동시 처리군(258.0 ± 80.0, P<0.05)은 당뇨 대조군(402.3 ± 42.6)에 비해 유의적으로 낮은 수치를 나타냈으며 후처리군의 경우에도 20일이 지난 시점에 혈당이 많이 감소되어 있음이 나타났다(288.3 ± 56.8, P=0.0532).7 shows the weight change. The experimental animal group treated with streptozotocin (25 mg / kg) showed no tendency to gain weight but rather decreased slightly compared to the untreated animal group. At 15 days after the experiment, there was no significant difference between the diabetic control group and the treatment group, but the weight gain was slightly increased in the simultaneous treatment group and the post-treatment group. 8 shows the change in blood glucose. During the experiment, the blood glucose level of the diabetic control group was higher than that of the other groups, and the blood glucose level of the diabetic control group was suppressed from 3 weeks after the administration of the sample. On the 20th day, the co-treated group (258.0 ± 80.0, P <0.05) showed significantly lower values than the diabetic control group (402.3 ± 42.6). Yes (288.3 ± 56.8, P = 0.0532).
표 3은 실험 종료시의 공복시 혈당과 체중을 나타낸 것이다. 정상 대조군에 비해 당뇨 대조군의 공복시 혈당이 확연하게 상승되어 있음이 나타났다. 이에 반면, 당뇨 대조군에 비해 동시 처리군과 후처리군의 공복시 혈당은 크게 감소되어 있었다. 체중의 변화에 있어서는 당뇨 대조군에 비해 동시 처리군과 후처리군의 체중이 유의적으로 증가되어 있음을 보였다.Table 3 shows fasting blood glucose and body weight at the end of the experiment. Fasting blood glucose of the diabetic control group was significantly higher than that of the normal control group. On the other hand, fasting blood glucose was significantly decreased in the simultaneous and post-treatment groups compared to the diabetic control group. In the change of body weight, the body weight of the simultaneous treatment group and the post-treatment group was significantly increased compared to the diabetic control group.
실험예 3. 뇨 채취 분석 (Urine sampling)Experimental Example 3. Urine sampling
실험 종료 시점에서 랫트를 24시간 동안 대사장(metabolic cage)에 넣어 요 중 포도당을 측정하기 위하여 요를 받아 포도당 측정 키트(Trinder, Sigma사)로 당뇨를 측정하였다.At the end of the experiment, rats were placed in a metabolic cage for 24 hours to receive urine to measure glucose in the urine, and diabetes was measured using a glucose measurement kit (Trinder, Sigma).
표 4는 투여 종료 후 요 중 포도당의 농도를 나타낸 것이다. 정상 대조군에 비해 당뇨 대조군의 요 중 포도당의 농도가 확연하게 상승되어 있음이 나타났다. 당뇨 대조군에 비해 동시 처리군(5.8 ± 0.5)은 낮은 수치를 나타내었으며 후처리군 (10.6 ± 1.4)에서는 큰 변화를 보이지 않았다.Table 4 shows the urine glucose concentration after the end of the administration. Compared with the normal control group, the urine glucose level in the diabetic control group was significantly increased. Compared to the diabetic control group, the simultaneous treatment group (5.8 ± 0.5) showed lower values and the post-treatment group (10.6 ± 1.4) did not show any significant change.
실험예 4. 신장 비대 지수(Kidney Hypertrophy Index) 측정Experimental Example 4. Measurement of Kidney Hypertrophy Index
투여 종료 시점에 랫트를 희생시켜 신장비대(kidney hypertrophy)를 측정하기 위하여, 신장을 제거하여 체중, 신장무게를 측정한 후, 신장비대율(%, 전체 체중에 대한 신장의 무게 백분율)을 계산하였다.In order to measure kidney hypertrophy at the end of dosing, rats were sacrificed to measure kidney hypertrophy, and the kidneys were removed to measure their weight and weight, and then the percent kidney ratio (%, weight percentage of total weight to total weight) was calculated.
표 5는 투여 종료 후, 신장비대 결과를 그룹간 비교한 것이다. 정상 대조군에 비해 당뇨 대조군의 신장비대는 높은 수치를 나타내었고 당뇨 대조군에 비해 동시 처리군과 후처리군은 각각 11.6%와 10.2%로 낮은 수치를 나타내어 신장 비대가 개선된 것으로 사료된다.Table 5 compares the results of renal hypertrophy between groups after the end of the administration. The renal hypertrophy of the diabetic control group was higher than that of the normal control group and the renal hypertrophy of the diabetic control group was 11.6% and 10.2%, respectively.
실험예 5. 급성독성시험Experimental Example 5. Acute Toxicity Test
1. 경구투여1. Oral administration
ICR계 마우스와 스프라그 도올리 랫트를 각각 10마리씩 4군으로 나누어 본 발명의 화살나무 물추출물을 각각 500, 725, 1000 및 5000 ㎎/㎏의 용량으로 경구 투여한 후 2주간 독성여부를 관찰한 결과 4군 모두에서 사망한 예가 한 마리도 없었고 외견상 대조군과 별다른 증상을 찾아볼 수 없었다.ICR-based mice and Sprague-Dawley rats were divided into four groups of 10 rats each, followed by oral administration of arrowwood water extracts of the present invention at doses of 500, 725, 1000 and 5000 mg / kg, respectively. As a result, none of the four groups died, and no symptoms were apparent from the control group.
2. 복강투여2. Intraperitoneal administration
ICR계 마우스(몸무게 25 ± 5 g)와 스프라그 도올리 랫트를 각각 10마리씩 4군으로 나누어 본 발명의 화살나무 물추출물을 각각 25, 250, 500 및 725 ㎎/㎏의 용량으로 복강투여한 후 24시간 동안 독성여부를 관찰한 결과 4군 모두에서 사망한 예가 한 마리도 없었고 외견상 대조군과 별다른 증상을 찾아볼 수 없었다. 실험 결과, 본 발명의 개다래 추출물은 급성독성이 거의 없음이 확인되었다.ICR mice (weight 25 ± 5 g) and Sprague dooli rats were divided into four groups of 10 rats each, followed by intraperitoneal administration of the arrowwood extract of the present invention at doses of 25, 250, 500 and 725 mg / kg, respectively. For 24 hours, no toxicities were observed in all four groups and no symptoms were apparent from the control group. As a result, it was confirmed that the extract of the present invention of the present invention has little acute toxicity.
하기의 상기 약학적 제제의 제제 예를 설명하나, 이는 본 발명을 한정하고자 함이 아닌 단지 구체적으로 설명하고자 함이다.Examples of the formulations of the above pharmaceutical formulations are described below, but are not intended to limit the present invention but to explain in detail only.
제제예 1. 주사제제의 제조Formulation Example 1 Preparation of Injection
실시예 2 화살나무 물추출물....................100㎎Example 2 Arrowwood extract ..... 100 mg
소디움 메타비설파이트........................3.0㎎Sodium metabisulfite ........ 3.0mg
메틸파라벤...................................0.8㎎Methylparaben ............... 0.8 mg
프로필파라벤.................................0.1㎎Propylparaben ...................... 0.1 mg
주사용 멸균증류수...........................적량Sterile distilled water for injection ..............
상기의 성분을 혼합하고 통상의 방법으로 2㎖로 한 후, 2㎖ 용량의 앰플에 충전하고 멸균하여 주사제를 제조한다.The above ingredients are mixed and made into 2 ml by a conventional method, and then filled into 2 ml ampoules and sterilized to prepare an injection.
제제예 2. 정제의 제조Formulation Example 2 Preparation of Tablet
실시예 2 화살나무 물추출물..................200㎎Example 2 Arrowwood Water Extract ... 200 mg
유당........................................100㎎Lactose 100 mg
전분........................................100㎎Starch .............................. 100 mg
스테아린산 마그네슘.........................적량Magnesium Stearate ...............
상기의 성분을 혼합하고 통상의 정제의 제조방법에 따라서 타정하여 정제를 제조한다.The above components are mixed and tableted according to a conventional method for producing tablets to produce tablets.
제제예 3. 캡슐제의 제조Formulation Example 3 Preparation of Capsule
실시예 2 화살나무 물추출물.................100㎎Example 2 Arrowwood Water Extract ... 100 mg
유당........................................50㎎Lactose 50 mg
전분........................................50㎎Starch ........................................ 50 mg
탈크........................................2㎎Talc ........................................ 2mg
스테아린산마그네슘......................... 적량Magnesium Stearate ...............
상기의 성분을 혼합하고 통상의 캡슐제의 제조방법에 따라서 젤라틴 캡슐에 충전하여 캡슐제를 제조한다.Capsules are prepared by mixing the above ingredients and filling into gelatin capsules according to a conventional method for preparing capsules.
제제예 4. 액제의 제조Formulation Example 4 Preparation of Liquid
실시예 2 화살나무 물추출물.................1000㎎Example 2 Arrowwood Water Extract...
설탕........................................20gSugar .................................. 20g
이성화당....................................20gIsomerized sugar ......................................... 20 g
레몬향......................................적량Lemon Flavor ......................
정제수를 가하여 전체........................100㎖Purified water is added to the whole ........... 100ml
상기의 성분을 통상의 액제의 제조방법에 따라서 혼합하고 100㎖의 갈색병에 충전하고 멸균시켜서 액제를 제조한다.The above components are mixed according to a conventional method for preparing a liquid, filled into a 100 ml brown bottle, and sterilized to prepare a liquid.
본 발명에 따른 화살나무의 극성용매가용추출물은 OGTT 시험, 스트렙토조토신 유도 당뇨 랫트에서 항당뇨활성을 보이고, 혈당 및 뇨당을 유의성있게 감소시켜 당뇨병 질환의 예방 및 치료에 효과적으로 사용할 수 있다.The polar solvent soluble extract of the arrowwood according to the present invention shows antidiabetic activity in the OGTT test, streptozotocin-induced diabetic rats, and can be effectively used for the prevention and treatment of diabetes diseases by significantly reducing blood glucose and urine glucose.
Claims (7)
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Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR100796457B1 (en) * | 2006-05-29 | 2008-01-21 | 경희대학교 산학협력단 | A composition comprising mixed herbal extract for the prevention and treatment of diabetes mellitus |
US20110027305A1 (en) * | 2009-08-03 | 2011-02-03 | Dai Han Pharm. Do., Ltd. | Composition Comprising an Extract of Herbal Combination Thereof for Preventing and Treating Diabetes Mellitus |
-
2003
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Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR100796457B1 (en) * | 2006-05-29 | 2008-01-21 | 경희대학교 산학협력단 | A composition comprising mixed herbal extract for the prevention and treatment of diabetes mellitus |
US20110027305A1 (en) * | 2009-08-03 | 2011-02-03 | Dai Han Pharm. Do., Ltd. | Composition Comprising an Extract of Herbal Combination Thereof for Preventing and Treating Diabetes Mellitus |
CN101987169A (en) * | 2009-08-03 | 2011-03-23 | 大韩药品工业株式会社 | Composition comprising an extract of herbal combination thereof for preventing and treating diabetes mellitus |
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