KR20030068608A - Pharmaceutical Composition Comprising Cumambrin A for Lowering Level of Blood Glucose - Google Patents

Pharmaceutical Composition Comprising Cumambrin A for Lowering Level of Blood Glucose Download PDF

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KR20030068608A
KR20030068608A KR1020020008065A KR20020008065A KR20030068608A KR 20030068608 A KR20030068608 A KR 20030068608A KR 1020020008065 A KR1020020008065 A KR 1020020008065A KR 20020008065 A KR20020008065 A KR 20020008065A KR 20030068608 A KR20030068608 A KR 20030068608A
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cumambrin
pharmaceutical composition
blood glucose
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cumambrine
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백현숙
박영미
성혜영
전숙자
홍용근
박기훈
양민석
박윤배
이종록
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경상남도
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
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    • A23LFOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/105Plant extracts, their artificial duplicates or their derivatives
    • AHUMAN NECESSITIES
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    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
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    • AHUMAN NECESSITIES
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    • A23VINDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00Food compositions, function of food ingredients or processes for food or foodstuffs
    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23VINDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2200/00Function of food ingredients
    • A23V2200/30Foods, ingredients or supplements having a functional effect on health
    • A23V2200/328Foods, ingredients or supplements having a functional effect on health having effect on glycaemic control and diabetes

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Abstract

PURPOSE: Provided is a pharmaceutical composition comprising cumambrin A or a Chryanthenum boreale M. extract containing cumambrin A as an active ingredient for lowering blood glucose level. The cumambrin A is also used as a health supplement food and a food additive. CONSTITUTION: A pharmaceutical composition for lowering blood glucose level is characteristically composed of cumambrin A or a Chryanthenum boreale M. extract containing cumambrin A, and pharmaceutically acceptable carrier.

Description

큐맘브린 A를 함유하는 혈당강하용 의약 조성물 {Pharmaceutical Composition Comprising Cumambrin A for Lowering Level of Blood Glucose}Pharmaceutical Composition Comprising Cumambrin A for Lowering Level of Blood Glucose}

본 발명은 혈당을 강하시키는데 유용한 큐맘브린 A(cumambrin A) 및 유효 성분으로서 큐맘브린 A를 함유하는 산국 추출물의 의약 조성물에 관한 것이다.The present invention relates to a pharmaceutical composition of cumambrin A, which is useful for lowering blood sugar, and an acid extract containing cumambrin A as an active ingredient.

현재 사용되고 있는 합성 혈당강하제로서는 환자의 증상에 따라 췌장의 β-세포에서 이미 만들어진 인슐린의 분비를 촉진시키는 설포닐우레아(Sulfonylurea) 계열 약물, 포도당과 같은 단당류의 흡수를 억제하며 포도당의 이용을 증가시키고 간에서 포도당의 생성을 억제시키는 비구아나이드(Biguanide) 계열 약물, 인슐린의 내성을 감소시키고 인슐린 작용을 증가시키는 시글리타존(Ciglitazone) 계열 약물, 인슐린의 활성을 증가시키는 트리글리타존(Triglitazone) 계열 약물 그리고 글루카곤 길항제등이 사용되고 있다. 그러나 알려진 이들 약제는 일반적으로 약한 활성을 나타내거나, 빈번한 부작용을 일으킨다는 결점을 가지고 있다.Synthetic hypoglycemic agents currently used include the use of sulfonylurea-based drugs that promote the secretion of insulin already made by the pancreatic β-cells according to the symptoms of the patient, inhibit the absorption of monosaccharides such as glucose, increase glucose utilization, Biguanide-based drugs that inhibit the production of glucose in the liver, Ciglitazone-based drugs that reduce insulin resistance and increase insulin action, Triglitazone-based drugs that increase insulin activity, and Glucagon antagonists are used. However, these known agents generally have the drawback of showing weak activity or causing frequent side effects.

예를 들면, 비구아나이드계열 약물은 유산증(lactic acidosis)에 기인한 심각한 부작용을 가지고 있으며, 설포닐우레아 계열 약물은 단순히 췌장에서 이미 만들어진 인슐린의 분비만 촉진시키므로 인슐린의 활성과 수용체에 문제가 있는 비인슐린 의존성 당뇨병 환자의 치료에는 한계가 있는 것으로 알려져 있다.For example, biguanide-based drugs have serious side effects due to lactic acidosis, and sulfonylurea-based drugs only promote the secretion of insulin already made in the pancreas, which is a problem that affects insulin activity and receptors. There is a known limitation in the treatment of insulin-dependent diabetics.

상술한 바와 같이, 알려진 당뇨병 치료제는 이들의 부작용과 약리효과의 한계 때문에 투여 방법을 고려하여 한정적으로 사용하고 있다.As described above, known antidiabetic agents are limited in consideration of their administration method due to their side effects and limitations of pharmacological effects.

따라서 안전성이 보장되는 천연자원으로 부터 혈당강하제를 개발하는 것은 매우 중요한 의미를 지닌다.Therefore, it is very important to develop hypoglycemic agents from natural resources with safety.

본 발명은 상기 언급한 기존 혈당강하제의 부작용이 감소된, 큐맘브린 A 또는 유효 성분으로서 큐맘브린 A를 함유하는 산국 추출물을 함유하는 혈당강하용 의약 조성물, 건강 보조 식품 및 식품 첨가물을 제공하는데 그 목적이 있다.The present invention provides a pharmaceutical composition for lowering blood glucose, a dietary supplement, and a food additive containing cumumbrin A or an acid extract containing cumambrin A as an active ingredient, wherein the side effects of the aforementioned conventional hypoglycemic agents are reduced. There is this.

도 1은 큐맘브린 A의1H-NMR 스펙트럼.1 is a 1 H-NMR spectrum of cumambrin A. FIG.

도 2는 스트랩토조토신으로 유발된 당뇨병 쥐에서 큐맘브린 A를 유효 성분으로 함유하는 산국 추출물의 혈당강하 효과를 나타낸 그래프.Figure 2 is a graph showing the hypoglycemic effect of acid extracts containing cumambrin A as an active ingredient in diabetic rats induced with straptozotocin.

본 발명자들은 상기 목적을 달성하고자 연구를 거듭한 결과, 산국으로부터 분리된 큐맘브린 A 또는 유효 성분으로서 큐맘브린 A를 함유하는 산국 추출물의 의약리학적 및 영양학적 용도를 개발하기 위하여 큐맘브린 A의 약리효과 및 안전성을 조사해 본 결과, 당뇨병에서 현저한 혈당강하 작용을 나타내고 있어 큐맘브린 A 또는 유효 성분으로서 큐맘브린 A를 함유하는 산국 추출물이 혈당강하용 의약은 물론, 건강 보조 식품 및 식품 첨가물로 사용될 수 있음을 확신하고, 본 발명을 완성하게 되었다.The present inventors have conducted research to achieve the above object, and as a result, pharmacological pharmacology of cumambrine A for the development of pharmacological and nutritional use of cumambrine A isolated from acidic country or cuminbrine A containing cumambrine A as an active ingredient Investigation of the effects and safety has shown a significant hypoglycemic activity in diabetes mellitus, can be used as cumulbrine A or acid extract containing cumambrine A as an active ingredient, as a dietary supplement and food additives, as well as drugs for hypoglycemia It is convinced that the present invention has been completed.

본 발명의 첫 번째 목적은 큐맘브린 A 또는 유효 성분으로서 큐맘브린 A를 함유하는 산국 추출물, 및 약제학적으로 허용되는 담체를 포함하는 혈당강하용 의약 조성물을 제공하는 것이다.A first object of the present invention is to provide a pharmaceutical composition for lowering blood sugar, which comprises cumumbrin A or an acid extract containing cumambrin A as an active ingredient, and a pharmaceutically acceptable carrier.

본 발명의 두 번째 목적은 유효 성분으로서 큐맘브린 A를 함유하는 산국 추출물을 함유하는 혈당강하용 건강 보조 식품을 제공하는 것이다.A second object of the present invention is to provide a hypoglycemic dietary supplement containing an acid extract containing cumam brine A as an active ingredient.

본 발명의 세 번째 목적은 유효 성분으로서 큐맘브린 A를 함유하는 산국 추출물을 함유하는 혈당강하용 식품 첨가물을 제공하는 것이다.A third object of the present invention is to provide a blood glucose lowering food additive containing an acid extract containing cumumbrin A as an active ingredient.

본 발명에 따라 산국 (Chrysanthemum borealeM.)으로부터 분리된 물질은 혈당강하 효과를 나타낸다. 이 물질은 5원고리, 7원고리 및 5원고리로 이루어진 구아노라이드 세스퀴터펜 락톤구조를 가지고 있는 큐맘브린 A로 밝혀져 있으며, Haruna, M 등의 문헌[Phytochemistry20, 2583, 1981]에 의해 크리산세뮴 코로나리움(Chrysanthemum coronarium)에서 분리된 것으로 처음보고 되었으며, 그 후 Douglas E. A. R. 등의 문헌[Phytochemistry31, 2165, 1992]에 의해 에리오세팔루스 펑츌라투스 (Eriocephalus punctulatus)에서 분리된 것으로 보고되고 있다. 산국에서는 본 발명자에 의해 최초로 큐맘브린 A가 분리되었으며, 고혈압 치료 효과가 있는 것으로 알려졌다 (대한민국 특허 출원 제2000-6958호 참조).The substance isolated from Chrysanthemum boreale M. according to the invention exhibits a hypoglycemic effect. This material is 5-membered ring, 7-membered ring and five won has been shown to kyumam Dublin A having a guano fluoride sesquioleate terpene lactone structure consisting of a ring, Haruna, Cri by the literature [Phytochemistry 20, 2583, 1981], such as M It was first reported as isolated from Chrysanthemum coronarium and has since been reported to be isolated from Eriocephalus punctulatus by Douglas EAR et al. ( Phytochemistry 31, 2165, 1992). . In the production country, the cumambrin A was first isolated by the present inventors, and it is known that it has an antihypertensive effect (see Korean Patent Application No. 2000-6958).

큐맘브린 A를 함유하는 산국은 국화과의 다년생 식물로서 산이나 밭둑에서 자라며, 높이는 1 ∼ 1.5m로서 많은 가지가 갈라진다. 잎은 길이 5 ∼ 7 cm에서 깊게 5개로 갈라지며, 뒷면에 부드러운 털이 있다. 지름 1 ∼ 1.5 cm 정도의 노란 꽃을 9 ∼ 10 월에 피운다.Mountain country containing cumam brine A is a perennial plant of Asteraceae, grows on mountain or field bank, and its height is 1 ~ 1.5m and many branches are split. The leaves are divided into 5 deep at 5 ~ 7 cm in length with soft hairs on the back. Yellow flowers about 1-1.5 cm in diameter bloom in September-October.

큐맘브린 A는 건조 분쇄된 산국의 꽃잎과 잎을 환류 하에 클로로포름 혹은 에틸아세테이트 극성 수준을 갖는 용매로 장시간 (약 24시간) 동안 수회 반복 추출한다. 여과된 추출액을 감압농축시켜 조추출물을 얻는다. 이 농축물을 유기·생리 활성 물질의 통상적인 정제 방법 중 하나인 유기용매의 농도구배를 사용한 실리카-겔 칼럼 크로마토그래피로 정제하여 큐맘브린 A를 얻는다. 필요에 따라 크로마토그래피 조건을 달리하여 더욱 정제된 추출물을 얻을 수 있다.Cumambrin A is repeatedly extracted several times over a long period of time (about 24 hours) with a solvent having a chloroform or ethyl acetate polarity level under reflux of the petals and leaves of the dry ground acid. The filtered extract was concentrated under reduced pressure to obtain a crude extract. This concentrate is purified by silica-gel column chromatography using a concentration gradient of an organic solvent, which is one of the usual purification methods for organic and physiologically active substances, to obtain cumambrine A. If necessary, chromatographic conditions may be changed to obtain a more purified extract.

분리된 큐맘브린 A는 자외선 스펙트럼, 적외선 스펙트럼, 핵자기공명분광(1H NMR,13C NMR, DEPT 90, 135,1H-13C COSY,1H-1H COSY)스펙트럼, 질량스펙트럼 데이터 및 기타 이화학적 데이터를 분석·종합한 결과, 5원고리, 7원고리 및 5원고리가 순서대로 융합되어 이루어져 있는 하기 화학식 1의 구아노라이드 세스퀴터펜 락톤구조를 갖는 것으로 밝혀져 있다. 하기 화학식 1에서 화합물 체계는 J. Williams의 J. A. C. S. 제 106호, 4895 ∼ 4902 페이지(1984)에 기재되어 있는 방식에 따른 것이다.Isolated cumambrin A is characterized by ultraviolet spectrum, infrared spectrum, nuclear magnetic resonance spectroscopy ( 1 H NMR, 13 C NMR, DEPT 90, 135, 1 H- 13 C COZY, 1 H- 1 H COZY) spectrum, mass spectrum data and As a result of analyzing and synthesizing other physicochemical data, it has been found to have a guanolide sesquiterpene lactone structure of the following Chemical Formula 1 in which five ring, seven ring and five ring are fused in order. The compound system in Formula 1 is according to the manner described in J. Williams, JACS 106, 4895-4902 (1984).

본 발명은 당대사성 질환의 예방 및 치료를 위해 큐맘브린 A를 함유하는 의약 조성물의 활성을 조사함으로써, 영양학적 및 의·약리학적 적용 가능성을 확인하였다.The present invention confirmed the nutritional and medical and pharmacological applicability by investigating the activity of a pharmaceutical composition containing cumambrine A for the prevention and treatment of glycemic metabolic diseases.

순수분리된 큐맘브린 A 또는 유효 성분으로서 큐맘브린 A를 함유하는 산국 추출물의 혈당강하 작용에 대한 효과를 조사한 결과, 스트렙토조토신 (STZ)의 투여에 의해 유발된 당뇨병 쥐의 혈당을 감소시키는 탁월한 기능을 나타내었으며, 이의 작용은 농도 의존적인 경향을 나타내었다. 또한, 혈당강하 작용 후 초기 혈당으로 회복되는데 최소한 24시간 정도가 소요되었으며 회복되는 경향은 투여 농도에 관계없이 같은 경향을 나타내었다.Investigation of the effect on the hypoglycemic effect of purely isolated cumambrine A or acid extract containing cumambrine A as an active ingredient resulted in an excellent function of reducing blood sugar levels in diabetic rats induced by administration of streptozotocin (STZ). Its action showed a concentration-dependent trend. In addition, it took at least 24 hours to recover the initial blood glucose after the hypoglycemic action, and the tendency to recover was the same regardless of the administration concentration.

상술한 바와 같이, 본원 발명에서는 큐맘브린 A 또는 유효 성분으로서 큐맘브린 A를 함유하는 산국 추출물이 혈당을 강하시킬 수 있음을 확인하였다.As described above, in the present invention, it was confirmed that acid extracts containing cumambrin A or cumambrin A as an active ingredient can lower blood sugar.

혈당강하 활성을 갖는 큐맘브린 A를 포함하는 본 발명의 의약 조성물은 선행 기술 분야에서 흔히 사용되고 있는, 경구 또는 비경구로 투여할 수 있는 여러 형태로 제형화할 수 있으며, 당분야에 널리 알려진 통상적인 방법 및 공정 기술을 이용하여 큐맘브린 A를 포함하는 건강 보조 식품 및 식품 첨가물로도 제조할 수 있다.The pharmaceutical composition of the present invention comprising cumambrine A having hypoglycemic activity may be formulated in various forms that can be administered orally or parenterally, which are commonly used in the art, and are well known in the art and Process technology can also be used to make dietary supplements and food additives, including cumambrine A.

큐맘브린 A 추출물은 약제학적 또는 식용으로 허용가능한 담체인 결합제 (예, 폴리비닐 피롤리돈, 하이드록시 프로필 셀롤로오즈), 붕해제 (예, 카르복시 메틸 셀룰로오스 칼슘, 전분 글리콜산 나트륨), 희석제 (예, 옥수수 전분, 유당, 콩기름, 결정 셀룰로오스, 만니톨), 활택제 (예, 스테아린산 미그네슘, 탈크), 감미제 (예, 백당, 과당, 솔비톨, 아스파탐), 안정제 (카르복시 메틸 셀룰로오스 나트륨, 알파 또는 베타 싸이클로 덱스트린, 비타민 C, 구연산, 백납), 보존제 (예, 파라옥시 안식향산 메틸, 파라옥시 안식향산 프로필, 안식향산 나트륨) 및 향료 (예, 에틸바닐린, 마스킹 후레바, 멘톨후라보노, 허브향)와 혼합하여, 정제, 시럽제, 캅셀제, 연질 캅셀제, 액제 또는 주사제와 같은 제제 및 다양한 식음료용으로 제조될 수 있다.Cumambrin A extract can be used as a pharmaceutical or edible acceptable carrier for binding agents (e.g. polyvinyl pyrrolidone, hydroxy propyl cellulose), disintegrants (e.g. carboxy methyl cellulose calcium, sodium starch glycolate), diluents ( Eg corn starch, lactose, soybean oil, crystalline cellulose, mannitol), glidants (e.g. magnesium stearate, talc), sweeteners (e.g. white sugar, fructose, sorbitol, aspartame), stabilizers (sodium carboxymethyl cellulose, alpha or Mixed with beta-cyclodextrin, vitamin C, citric acid, white lead), preservatives (e.g. methyl paraoxy benzoate, paraoxy benzoic acid propyl, sodium benzoate) and flavorings (e.g. ethyl vanillin, masking flavor, menthol flavono, herbal flavor) Thus, it can be prepared for preparations such as tablets, syrups, capsules, soft capsules, liquids or injections, and various food and beverages.

<제제예><Example

제제 1: 정제Formulation 1: Tablet

큐맘브린 A 1 내지 100 mg, 락토즈 77 mg, 결정성 셀룰로오스 15 mg, 옥수수 전분 7 mg을 완전히 혼합한 다음, 혼합물은 회전식 타정기로 타정하여 직경이 7 mm 및 15 mm이고 중량이 150, 200, 250, 500 mg인 정제를 수득한다.After thoroughly mixing 1-100 mg of cumambrine A, 77 mg lactose, 15 mg crystalline cellulose and 7 mg corn starch, the mixture was compressed into a rotary tableting machine, 7 mm and 15 mm in diameter, weighing 150, 200, 250, 500 mg tablets are obtained.

제제 2: 시럽제Formulation 2: Syrup

큐맘브린 A 1 내지 100 mg, 정제당 30 g, 70w/v% D-소르비톨 25 g, 에틸 p-히드록시벤조에이트 0.03 g을 온수 60 ml에 용해시킨다. 용액을 냉각시킨 후 글리세롤 0.15 g 및 96% 에탄올 0.5 g 중의 향미제 0.2 g 용액을 가한다. 전체 혼합물을 물로 희석하여 100 ml로 만든다.Dissolve 1 to 100 mg of cumambrine A, 30 g per tablet, 25 g of 70w / v% D-sorbitol and 0.03 g of ethyl p-hydroxybenzoate in 60 ml of warm water. After the solution is cooled, a solution of 0.2 g of flavor in 0.15 g of glycerol and 0.5 g of 96% ethanol is added. The whole mixture is diluted with water to 100 ml.

제제 3: 주사용 액제Formulation 3: Injectable Liquid

큐맘브린 A 1 내지 100 mg을 8% 프로필렌글리콜에 용해시켜 1 ml로 만든다.Dissolve 1-100 mg of cumambrine A in 8 ml propylene glycol to make 1 ml.

큐맘브린 A의 투여량은 투여 방식 및 경로, 복용자의 연령, 체중 및 건강, 증상의 상태 및 정도와 같은 요소에 따라 상이할 수 있다. 혈당강하에 이용하기 위하여, 본 발명의 화합물은 예를 들어 체중 1 kg 당 약 1 내지 100 mg의 유효 성분 투여량으로 일일 경구 투여할 수 있다. 통상적으로 일일 1 내지 3 회 분할 투여 또는 서방성 제제로 300 내지 500 mg/kg/일, 최대 1000 mg/kg/일의 투여량이 원하는 약리학적 효과를 달성하는데 효과적이다.Dosage of cumambrine A may vary depending on factors such as the mode and route of administration, the age, weight and health of the recipient, the condition and extent of symptoms. For use in hypoglycemia, the compounds of the present invention can be administered orally daily, for example, at an active ingredient dosage of about 1 to 100 mg per kg of body weight. Typically dosages of 300 to 500 mg / kg / day, up to 1000 mg / kg / day in 1 to 3 divided doses or sustained release formulations are effective to achieve the desired pharmacological effect.

이하, 본 발명을 실시예를 들어 더욱 상세히 설명하고자 한다. 그러나, 이들 실시예에 의해 본 발명의 범위를 제한하고자 하는 것은 아니다.Hereinafter, the present invention will be described in more detail with reference to Examples. However, these examples are not intended to limit the scope of the present invention.

<실시예><Example>

<실시예 1: 산국으로부터 유효 성분으로서 큐맘브린 A를 함유하는 추출물 분리>Example 1 Isolation of Extract Containing Cumambrin A as Active Ingredient from Country of Origin

그늘에서 잘 말리고 잘게 부순 산국 전초(全草) 1 kg에 90% 에탄올(주정) 10 L를 넣고, 35∼40℃에서 7일간 추출하였다. 여과한 추출액을 40℃에서 감압하에 농축시켜 추출액 부피가 1.5 L 되도록 하였다. 농축한 추출액에 물 1 L를 넣고 1시간동안 진탕시켰다. 추출액을 원심분리(5000 rpm)시켜 상등액과 침전물로 분리하였다. 분리된 침전물에 30% 에탄올 1 L을 넣고 30분간 진탕시킨 후 원심분리시켰다. 침전물을 여과 분리하고, 진공 건조시켜 유효 성분으로서 86 g의 큐맘브린 A를 함유하는 산국 추출물을 얻었다.10 L of 90% ethanol (alcohol) was added to 1 kg of dried starch outpost, which was dried well in the shade, and extracted at 35-40 ° C. for 7 days. The filtered extract was concentrated at 40 ° C. under reduced pressure so that the volume of the extract was 1.5 L. 1 L of water was added to the concentrated extract and shaken for 1 hour. The extract was centrifuged (5000 rpm) to separate the supernatant and precipitate. 1 L of 30% ethanol was added to the separated precipitate, followed by shaking for 30 minutes, followed by centrifugation. The precipitate was separated by filtration and dried in vacuo to give an acid extract containing 86 g of cumambrine A as an active ingredient.

상기 실시예는 산국 전초에만 국한되는 것이 아니다. 이 실시예를 산국의 꽃잎, 줄기, 잎 등 산국 부위별로 적용하여 얻을 수도 있다.The above embodiment is not limited to the country outpost. This embodiment can also be obtained by applying the country of origin, such as petals, stems, leaves.

<실시예 2: 유효 성분으로서 큐맘브린 A를 함유하는 산국 추출물의 혈당강하효과>Example 2: Hypoglycemic Effect of Acid Extracts Containing Cumambrine A as Active Ingredient

도 2에서 볼 수 있는 바와 같이 유효 성분으로서 큐맘브린 A를 함유하는 산국 추출물은 스트렙토조토신 (STZ)으로 유발된 당뇨병 쥐의 혈당을, 투여 후 30분 경부터 감소시키기 시작하여 투여 후 6 내지 7시간 경에 최대 강하 효과 (470±25→170±17 mg/dl)를 보였으며, 7시간 경과 후부터 서서히 회복하여 24시간 경에 초기의 혈당으로 회복됨으로써 작용 지속시간이 12시간 이상이었다. 또한 혈당강하 작용의 경향은 농도 의존적인 경향을 나타내었다. 또한, 1 그램/체중 킬로그램을 투여했을 때 혈당강하효과는 초기에는 100 밀리그램/체중 킬로그램을 투여했을 때보다 신속하고 강한 혈당강하 효과를 보였지만 저혈당증 유도는 동반되지 않았다.As can be seen in Figure 2, the acid extract containing cumambrin A as an active ingredient begins to reduce the blood sugar of streptozotocin (STZ) -induced diabetic rats from 30 minutes after administration, and 6 to 7 after administration. The maximum dropping effect (470 ± 25 → 170 ± 17 mg / dl) was observed over time, and after 7 hours, it gradually recovered and returned to the initial blood sugar at 24 hours. In addition, the hypoglycemic activity tended to be concentration dependent. In addition, the hypoglycemic effect when administered 1 gram / kilogram body weight initially showed a faster and stronger hypoglycemic effect than when administered 100 mg / kilogram body weight, but did not induce hypoglycemia.

<실시예 3: 큐맘브린 A의 세포독성검사>Example 3 Cytotoxicity Test of Cumambrin A

큐맘브린 A의 세포독성을 검사하기 위하여, 큐맘브린 A를 투여한 쥐에서 혈액 분석을 행하였다. 하기 표 1에 기재된 바와 같이 본 발명의 큐맘브린 A는 독성 효과를 나타내지 않았다.To test the cytotoxicity of cumambrin A, blood analysis was performed in mice administered cumumbrin A. As shown in Table 1, cumambrin A of the present invention did not show a toxic effect.

정상 범위Normal range 대조군Control 5mg/kg5mg / kg 10mg/kg10mg / kg 20mg/kg20mg / kg 5+5+10mg/kg5 + 5 + 10mg / kg TPTP 5.8-8.0g/dl5.8-8.0g / dl 7.1±0.277.1 ± 0.27 6.8±0.396.8 ± 0.39 6.8±0.26.8 ± 0.2 5.9±0.45.9 ± 0.4 6±06 ± 0 ALBALB 3.3-5.0g/dl3.3-5.0g / dl 3.8±0.093.8 ± 0.09 4.0±0.464.0 ± 0.46 4.1±0.34.1 ± 0.3 3.6±0.33.6 ± 0.3 3.5±03.5 ± 0 GLOGLO 2.0-3.6g/dl2.0-3.6 g / dl 3.2±0.163.2 ± 0.16 3.3±0.153.3 ± 0.15 3.2±0.343.2 ± 0.34 3.6±0.043.6 ± 0.04 3.5±03.5 ± 0 T-BILT-BIL 0.2-1.20.2-1.2 0.2±0.040.2 ± 0.04 0.2±0.040.2 ± 0.04 0.2±0.040.2 ± 0.04 0.2±00.2 ± 0 0.2±00.2 ± 0 D-BILD-BIL 0-0.50-0.5 0.27±0.020.27 ± 0.02 0.1±0.10.1 ± 0.1 0.1±0.080.1 ± 0.08 0.1±0.050.1 ± 0.05 0.1±00.1 ± 0 I-BILI-BIL 0.1-1.20.1-1.2 0.3±0.070.3 ± 0.07 0.3±0.140.3 ± 0.14 0.3±0.110.3 ± 0.11 0.2±0.050.2 ± 0.05 0.1±00.1 ± 0 GOTGOT 5-40유닛5-40 units 19.7±2.4419.7 ± 2.44 35.3±2.3835.3 ± 2.38 40.0±1.040.0 ± 1.0 39.3±3.3839.3 ± 3.38 26.5±3.526.5 ± 3.5 GPTGPT 3-35유닛3-35 units 14.3±4.4414.3 ± 4.44 22.8±2.1322.8 ± 2.13 26.0±2.026.0 ± 2.0 16.5±2.2516.5 ± 2.25 14±114 ± 1 LDHLDH 100-450유닛100-450 units 328.7±16.44328.7 ± 16.44 423.8±23.75423.8 ± 23.75 354.3±28.38354.3 ± 28.38 360.5±21.5360.5 ± 21.5 355±2.4355 ± 2.4 ALPALP 70-280유닛70-280 units 113.0±10.0113.0 ± 10.0 132.0±7.5132.0 ± 7.5 165.0±21.0165.0 ± 21.0 141.0±14.5141.0 ± 14.5 111±9111 ± 9 BUNBUN 10-20mg/dl10-20mg / dl 16.3±2.2216.3 ± 2.22 14.5±2.014.5 ± 2.0 15.6±3.1915.6 ± 3.19 18.5±3.9818.5 ± 3.98 18.5±3.218.5 ± 3.2 CRECRE 0.4-1.50.4-1.5 0.8±0.040.8 ± 0.04 0.7±00.7 ± 0 0.6±0.20.6 ± 0.2 0.8±0.080.8 ± 0.08 0.7±00.7 ± 0 GLUGLU 70-110mg/dl70-110mg / dl 90.0±3.3390.0 ± 3.33 91.5±691.5 ± 6 85.8±5.8885.8 ± 5.88 90.8±5.7590.8 ± 5.75 87.5±4.587.5 ± 4.5 TP: 트립토판, ALB: 알부민, GLO: 글리옥살라제, BIL: 빌리루빈,GOT 및 GPT: 간독성을 나타내는 지표, LDH: 젖산 탈수소 효소,ALP: 알칼린 포스파타제, BUN: 혈중 요소 질소, CRE: 크리아틴, GLU: 포도당TP: tryptophan, ALB: albumin, GLO: glyoxalase, BIL: bilirubin, GOT and GPT: indicators of hepatotoxicity, LDH: lactic acid dehydrogenase, ALP: alkaline phosphatase, BUN: urea nitrogen in blood, CRE: creatine , GLU: Glucose

이상에서 상세히 설명하고 입증한 바와 같이, 본 발명은 큐맘브린 A 또는 유효 성분으로서 큐맘브린 A를 함유하는 산국 추출물을 이용하여 혈당을 강하시킬 수 있음을 밝혔다. 특히 이 물질은 저혈당으로의 유도를 유발하지 않으며, 체내에서 가역적인 대사를 받음으로써 조직독성이 없는 것으로 나타났다. 이러한 작용은 기존의 혈당강하제의 부작용이 없는 혈당강하제, 건강 보조 식품 및 식품 첨가물로서의 용도를 제공한다.As described and demonstrated in detail above, the present invention was found to be able to lower blood sugar by using cumumbrin A or acid extract containing cumambrin A as an active ingredient. In particular, it did not induce hypoglycemia and was shown to be non-histotoxic by undergoing reversible metabolism in the body. This action provides use as a hypoglycemic agent, dietary supplement and food additive without the side effects of conventional hypoglycemic agents.

Claims (1)

큐맘브린 A 또는 큐맘브린 A 함유 산국 추출물, 및 약제학적으로 허용되는 담체를 포함하는 혈당강하용 의약 조성물.A pharmaceutical composition for lowering blood sugar, which comprises cumam brine A or cumam brine A-containing acid extract, and a pharmaceutically acceptable carrier.
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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN106333981A (en) * 2015-07-17 2017-01-18 中山大学 Anti-obesity drug containing wild chrysanthemum flower extract
CN106692125A (en) * 2015-07-17 2017-05-24 中山大学 Anti-diabetic drug containing wild chrysanthemum flower extract

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN106333981A (en) * 2015-07-17 2017-01-18 中山大学 Anti-obesity drug containing wild chrysanthemum flower extract
CN106692125A (en) * 2015-07-17 2017-05-24 中山大学 Anti-diabetic drug containing wild chrysanthemum flower extract

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