KR102567159B1 - Extract of Ligularia fischeriof as α-glucosidase inhibitor - Google Patents
Extract of Ligularia fischeriof as α-glucosidase inhibitor Download PDFInfo
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- KR102567159B1 KR102567159B1 KR1020200177845A KR20200177845A KR102567159B1 KR 102567159 B1 KR102567159 B1 KR 102567159B1 KR 1020200177845 A KR1020200177845 A KR 1020200177845A KR 20200177845 A KR20200177845 A KR 20200177845A KR 102567159 B1 KR102567159 B1 KR 102567159B1
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- Prior art keywords
- bear
- chloroform
- present
- stink
- diabetes
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- 229940077274 Alpha glucosidase inhibitor Drugs 0.000 title description 3
- 239000003888 alpha glucosidase inhibitor Substances 0.000 title description 3
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- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/105—Plant extracts, their artificial duplicates or their derivatives
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, 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
- A23L3/00—Preservation of foods or foodstuffs, in general, e.g. pasteurising, sterilising, specially adapted for foods or foodstuffs
- A23L3/40—Preservation of foods or foodstuffs, in general, e.g. pasteurising, sterilising, specially adapted for foods or foodstuffs by drying or kilning; Subsequent reconstitution
- A23L3/44—Freeze-drying
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/28—Asteraceae or Compositae (Aster or Sunflower family), e.g. chamomile, feverfew, yarrow or echinacea
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- A—HUMAN NECESSITIES
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- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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Abstract
본 발명은 곰취(Ligularia fischeri) 클로로포름 분획물을 유효성분으로 포함하는 당뇨 예방 및 치료용 조성물에 관한 것이다. 본 발명은 곰취를 70%주정 용매로 추출한 뒤 헥산, 클로로포름, 에틸 아세테이트, 부탄올을 이용하여 분획한 분획물의 알파-글루코시다제(α-glucosidase) 활성 저해효과를 비교한 결과, 클로로포름 분획물이 알파-글루코시다제(α-glucosidase)활성 저해효과가 가장 우수한 바, 본 발명은 당뇨병 치료 및 예방 용도로 유용하게 이용할 수 있는 효과가 있다. 본 발명의 방법으로 제조된 곰취 분획물은 당뇨병 치료 및 예방 위한 약학적 조성물, 식품 조성물로 유용하게 이용할 수 있는 효과가 있다. The present invention relates to a composition for preventing and treating diabetes comprising a chloroform fraction of bear stink ( Ligularia fischeri ) as an active ingredient. In the present invention, as a result of comparing the α-glucosidase activity inhibitory effect of fractions obtained by extracting bear stink with 70% alcohol solvent and fractionating using hexane, chloroform, ethyl acetate, and butanol, the chloroform fraction was found to be alpha- Glucosidase (α-glucosidase) activity inhibitory effect is the most excellent, the present invention has an effect that can be usefully used for the treatment and prevention of diabetes. The bear odor fraction prepared by the method of the present invention can be usefully used as a pharmaceutical composition or food composition for the treatment and prevention of diabetes.
Description
본 발명은 알파-글루코시다제에 대한 억제활성을 갖는 곰취(Ligularia fischeri) 추출물 및 이의 용도에 관한 것이다.The present invention relates to an extract of bear stink ( Ligularia fischeri ) having inhibitory activity against alpha-glucosidase and its use.
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 (microangiopathy), 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 plasma glucose levels in humans and mammals. This abnormal sugar level increases the level of hemoglobin in plasma, resulting in chronic hyperglycemia. ), atherosclerosis, microangiopathy, kidney disease, heart disease, diabetic retinopathy and other eye diseases.
진성 당뇨병(Diabetes mellitus)은 두가지 유형으로 특징지워지는데, 인슐린 의존형인 I형 당뇨병(insulin dependentdiabetes, IDDM)은 혈액 내의 글루코스 조절 호르몬인 인슐린(Insulin)의 분비 결핍으로 야기되며, 주로 10 내지 20대의 젊은 연령층에서 발병되기 때문에 소아당뇨병(juvenile diabetes)이라 불리우기도 한다. Ⅱ형 당뇨병(non-insulin dependent diabetes, NIDDM)은 주로 40대 이후에 발병되며, 우리나라 당뇨병 환자의 대부분을 차지한다. 제 Ⅰ형과는 달리 성인형 당뇨병이라 불리우며 발병 원인은 아직 명확히 밝혀져 있지 않으나, 유전적인 요인과 환경적 요소가 함께 관여되어 발생하는 것으로 알려졌다. 제 Ⅱ형 당뇨병의 병인으로 췌장베타세포에서 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), which is an insulin-dependent type, is caused by a secretion deficiency of insulin, a glucose-regulating hormone in the blood, and mainly affects young people in their 10s to 20s It is also called juvenile diabetes because it develops in all age groups. Type Ⅱ diabetes (non-insulin dependent diabetes, NIDDM) mainly occurs after the age of 40, and accounts for most of the diabetic patients in Korea. Unlike type I, it is called adult type diabetes, and the cause of the onset is not yet clear, but it is known that genetic and environmental factors are involved together. As the pathogenesis of type II diabetes, both impaired insulin secretion in pancreatic beta cells and defects in insulin action (insulin resistance) in target cells are observed.
현재 제 Ⅱ형 당뇨병 및 인슐린 저항성 같은 합병증에 사용되는 제제로는 5 종류의 화합물군, 즉 비구아니드(biguanides), 티아졸리딘디온 (thiazolidinediones), 설포닐우레아(sulfonylureas), 벤조산(benzoic acid) 유도체 화합물 및 α-글루코시다제 저해제(α-glucosidase inhibitor) 등이 사용되고 있으며, 이중 메트포민(metformin)과 같은 비구아니드 화합물은 과도한 혈액내 글루코네오제네시스(gluconeogenesis)를 예방하는 것으로 알려져 있다. 티아졸리딘디온 화합물은 말초 신경의 글루코스 소비율을 증가시키는 작용을 하는 것으로 생각되며, 톨부타미드(tolbutamide) 및 글리부리드(glyburide)와 같은 설포닐우레아, 레파글리니드(repaglinide) 화합물과 같은 벤조산 유도체 및 아카보스(acarbose)와 같은 α-글루코시다제 저해제는 인슐린 분비를 자극하여 혈장 글루코스를 낮추는 작용을 한다.There are five groups of compounds currently used for complications such as type II diabetes and insulin resistance: biguanides, thiazolidinediones, sulfonylureas, and benzoic acid. Derivative compounds and α-glucosidase inhibitors are used, and among them, biguanide compounds such as metformin are known to prevent excessive blood gluconeogenesis. Thiazolidinedione compounds are thought to act to increase the rate of glucose consumption of peripheral nerves, sulfonylureas such as tolbutamide and glyburide, and benzoic acids such as repaglinide compounds. α-glucosidase inhibitors such as derivatives and acarbose act to lower plasma glucose by stimulating insulin secretion.
한편, 곰취(Ligularia fischeri)는 국화과 곰취속에 속하는 여러해 살이 풀로서, 높이가 약 1 미터 정도까지 자란다. 깊은 산의 산비탈 풀밭의 약간 습한곳에서 자생하며, 이의 뿌리 줄기는 짧고 굵고 가늘고 긴 수염뿌리가 많이 나 있다. 심장형의 뿌리잎은 잎자루가 길고 가장자리에는 톱니가 나 있다. 보통 여름철 7~9월에 줄기 윗부분에 노란색 꽃이 촘촘히 모여 피는데 가장자리의 혀꽃은 5~9개가 나 있다. 최근에는 항암작용이 있는 것으로 밝혀져 건강식품으로도 가치가 높으며 진해, 거담, 진통, 혈액순환 촉진제로 이용된다. On the other hand, bear odor ( Ligularia fischeri ) is a perennial plant belonging to the genus Asteraceae and grows to about 1 meter in height. It grows wild in a slightly humid place in the hillside grass of a deep mountain, and its rhizome is short, thick, thin, and has many long beard roots. Heart-shaped radical leaves have long petioles and sawtooth edges. Usually, in summer, from July to September, yellow flowers are densely gathered on the upper part of the stem, and there are 5 to 9 tongue flowers on the edge. Recently, it has been found to have anti-cancer activity, so it is highly valued as a health food, and is used as an antitussive, expectorant, pain reliever, and blood circulation promoter.
그리고, 곰취에 당뇨 및 이에 의한 질환의 억제, 개선, 및 치료를 위해 유용하다고 1020090047638 A 부분에 나와있지만, 본 발명과 차이점은 본 발명은 곰취 추출물을 분획했을 때 클로로포름 분획물에서 알파-글루코시다제(α-glucosidase) 저해 활성이 뛰어난 효능을 나타냈다. In addition, it is stated in part A of 1020090047638 that bear stink is useful for suppressing, improving, and treating diabetes and diseases caused by it, but the difference from the present invention is that when the bear stink extract is fractionated, the alpha-glucosidase ( α-glucosidase) showed excellent efficacy in inhibitory activity.
이에 본 발명자들은 곰취 추출물의 클로로포름 분획물이 알파-글루코시다제(α-glucosidase) 저해 활성 억제를 위해 효능이 있음을 확인하고 본 발명을 완성하게 되었다.Accordingly, the present inventors confirmed that the chloroform fraction of the bear stinger extract was effective for inhibiting α-glucosidase inhibitory activity and completed the present invention.
1020090047638 A 1020090047638 A
본 발명의 목적은 곰취(Ligularia fischeri) 클로로포름 분획물을 유효성분으로 포함하는 당뇨병 예방 및 개선용 식품 조성물을 제공하는 것이다.An object of the present invention is to provide a food composition for the prevention and improvement of diabetes comprising a chloroform fraction of Ligularia fischeri as an active ingredient.
본 발명의 목적은 곰취(Ligularia fischeri) 클로로포름 분획물을 유효성분으로 포함하는, 당뇨병 예방, 개선 또는 치료에서 알파-글루코시다제(α-glucosidase) 활성을 억제하기 위한 약학적 조성물 제공 하는 것이다.An object of the present invention is to provide a pharmaceutical composition containing a chloroform fraction of Ligularia fischeri as an active ingredient for inhibiting α-glucosidase activity in preventing, improving or treating diabetes.
곰취(Ligularia fischeri) 클로로포름 분획물을 유효성분으로 포함하는 당뇨병 예방 또는 치료용 약학적 조성물 제공 하는 것이다.To provide a pharmaceutical composition for preventing or treating diabetes comprising a chloroform fraction of Ligularia fischeri as an active ingredient.
실험관 내에서 곰취 에탄올 추출물의 클로로포름 분획물을 시료에 처리하는 단계;를 포함하는 알파-글루코시다제 활성을 억제하는 방법을 제공 하는 것이다.It is to provide a method for inhibiting alpha-glucosidase activity, including treating the sample with the chloroform fraction of the ethanol extract of bear stipea in vitro.
본 발명은 곰취(Ligularia fischeri) 클로로포름 분획물을 유효성분으로 포함하는 당뇨병 예방 및 개선용 식품 조성물을 제공한다.The present invention provides a food composition for the prevention and improvement of diabetes comprising a chloroform fraction of Ligularia fischeri as an active ingredient.
본 발명은 곰취(Ligularia fischeri) 클로로포름 분획물을 유효성분으로 포함하는, 당뇨병 예방, 개선 또는 치료에서 알파-글루코시다제(α-glucosidase) 활성을 억제하기 위한 약학적 조성물 제공한다.The present invention provides a pharmaceutical composition for inhibiting α-glucosidase activity in preventing, improving or treating diabetes, comprising a chloroform fraction of bear stink ( Ligularia fischeri ) as an active ingredient.
본 발명은 곰취(Ligularia fischeri) 클로로포름 분획물을 유효성분으로 포함하는 당뇨병 예방 또는 치료용 약학적 조성물 제공한다.The present invention provides a pharmaceutical composition for preventing or treating diabetes comprising a chloroform fraction of Ligularia fischeri as an active ingredient.
본 발명은 실험관 내에서 곰취 에탄올 추출물의 클로로포름 분획물을 시료에 처리하는 단계;를 포함하는 알파-글루코시다제 활성을 억제하는 방법을 제공한다.The present invention provides a method for inhibiting alpha-glucosidase activity, comprising treating a sample with the chloroform fraction of the ethanol extract of bear stipea in vitro.
본 발명은 곰취를 70%주정 용매로 추출한 뒤 헥산, 클로로포름, 에틸 아세테이트, 부탄올을 이용하여 분획한 분획물의 알파-글루코시다제(α-glucosidase) 활성 저해효과를 비교한 결과, 클로로포름 분획물이 알파-글루코시다제(α-glucosidase)활성 저해효과가 가장 우수한 바, 본 발명의 곰취 클로로포름 분획물은 당뇨병 치료 및 예방 용도로 유용하게 이용할 수 있는 효과가 있다.In the present invention, as a result of comparing the α-glucosidase activity inhibitory effect of fractions obtained by extracting bear stink with 70% alcohol solvent and fractionating using hexane, chloroform, ethyl acetate, and butanol, the chloroform fraction was found to be alpha- Since it has the best inhibitory effect on α-glucosidase activity, the chloroform fraction of bear stinger of the present invention can be usefully used for the treatment and prevention of diabetes.
도 1은 곰취 분획물 제조방법을 나타낸 도이다.
도 2는 곰취 주정 추출물의 분획물의 알파-글루코시다제(α-glucosidase) 활성 저해효과를 측정을 타나낸 도이다.1 is a diagram showing a method for preparing a bear odor fraction.
Figure 2 is a diagram showing the measurement of the α-glucosidase activity inhibitory effect of the fractions of the extract of bear chinensis alcohol.
본 발명은 곰취 클로로포름 분획물을 유효성분으로 포함하는 당뇨병 예방 및 치료용 약학적 조성물을 제공한다.The present invention provides a pharmaceutical composition for preventing and treating diabetes comprising a chloroform fraction of bear odor as an active ingredient.
상기 분획물은 물,C1 내지 C4의 저급 알코올 및 저급 알코올 수용액으로 이루어진 군에서 선택된 용매로 추출되는 것일 수 있으며, 보다 바람직하게는 에탄올 추출물, 60% 내지 80%의 에탄올 추출물 또는 70% 에탄올 추출물의 클로로포름 분획물에 관한 것이다.The fraction may be extracted with a solvent selected from the group consisting of water, C1 to C4 lower alcohol and lower alcohol aqueous solution, more preferably ethanol extract, 60% to 80% ethanol extract or 70% chloroform of ethanol extract It's about fractions.
본 발명에서, 클로로포름 분획물은 에탄올로 곰취를 추출한 후, 헥산, 클로로포름, 에틸아세테이트 및 n-부탄올 분획물로 순차적으로 분획할 수 있고, 이 중, 클로로포름 분획물일 수 있다. In the present invention, the chloroform fraction may be sequentially fractionated into hexane, chloroform, ethyl acetate, and n-butanol fractions after extracting bear odor with ethanol, and among them, the chloroform fraction may be used.
상기 추출물은 곰취와 용매를 1:10의 부피비로 추출할 수 있다.The extract may be extracted with bear stink and the solvent at a volume ratio of 1:10.
상기 추출물은 곰취의 잎, 줄기, 뿌리, 열매 및 씨앗으로 이루어진 군으로부터 선택된 부위로 추출된 것일 수 있다.The extract may be extracted from a part selected from the group consisting of leaves, stems, roots, fruits and seeds of bear stink.
상기 조성물은 알파-글루코시다제(α-glucosidase) 활성 억제할 수 있어, 이를 당뇨병의 예방, 개선 또는 치료에 유용하게 사용할 수 있고, 당뇨병 예방 및 치료에 있어서, 알파-글루코시다제(α-glucosidase) 활성 억제에 대한 용도로 이용될 수 있다.The composition can inhibit alpha-glucosidase activity, so it can be usefully used for the prevention, improvement or treatment of diabetes, and in the prevention and treatment of diabetes, alpha-glucosidase (α-glucosidase) ) can be used for activity inhibition.
본 발명의 약학 조성물에는 유효성분 이외에 보조제(adjuvant)를 추가로 포함할 수 있다. 상기 보조제는 당해 기술분야에 알려진 것이라면 어느 것이나 제한 없이 사용할 수 있으나, 예를 들어 프로인트(Freund)의 완전 보조제 또는 불완전 보조제를 더 포함하여 그 면역성을 증가시킬 수 있다. The pharmaceutical composition of the present invention may further include an adjuvant in addition to the active ingredient. As long as the adjuvant is known in the art, any one may be used without limitation, but, for example, Freund's complete adjuvant or incomplete adjuvant may be further included to increase immunity.
본 발명에 따른 약학 조성물은 유효성분을 약학적으로 허용된 담체에 혼입시킨 형태로 제조될 수 있다. 여기서, 약학적으로 허용된 담체는 제약 분야에서 통상 사용되는 담체, 부형제 및 희석제를 포함한다. 본 발명의 약학 조성물에 이용할 수 있는 약학적으로 허용된 담체는 이들로 제한되는 것은 아니지만, 락토스, 덱스트로스, 수크로스, 솔비톨, 만니톨, 자일리톨, 에리스리톨, 말티톨, 전분, 아카시아 고무, 알지네이트, 젤라틴, 칼슘 포스페이트, 칼슘 실리케이트, 셀룰로스, 메틸 셀룰로스, 폴리비닐 피롤리돈, 물, 메틸히드록시벤조에이트, 프로필히드록시벤조에이트, 탈크, 마그네슘 스테아레이트 및 광물유를 들 수 있다.The pharmaceutical composition according to the present invention may be prepared in the form of incorporating the active ingredient into a pharmaceutically acceptable carrier. Here, the pharmaceutically acceptable carrier includes carriers, excipients and diluents commonly used in the pharmaceutical field. Pharmaceutically acceptable carriers usable in the pharmaceutical composition of the present invention include, but are not limited to, lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, gum acacia, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil.
본 발명의 약학 조성물은 각각 통상의 방법에 따라 산제, 과립제, 정제, 캡슐제, 현탁액, 에멀전, 시럽, 에어로졸 등의 경구형 제형, 외용제, 좌제 또는 멸균 주사용액의 형태로 제형화하여 사용될 수 있다.The pharmaceutical composition of the present invention may be formulated and used in the form of oral formulations such as powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols, external preparations, suppositories or sterile injection solutions according to conventional methods, respectively. .
제제화할 경우에는 통상 사용하는 충진제, 증량제, 결합제, 습윤제, 붕해제, 계면활성제 등의 희석제 또는 부형제를 사용하여 조제될 수 있다. 경구투여를 위한 고형제제에는 정제, 환제, 산제, 과립제, 캡슐제 등이 포함되며, 그러한 고형 제제는 유효성분에 적어도 하나 이상의 부형제, 예를 들면 전분, 칼슘 카르보네이트, 수크로스, 락토오스, 젤라틴 등을 섞어 조제될 수 있다. 또한, 단순한 부형제 이외에 마그네슘 스테아레이트, 탈크 같은 윤활제들도 사용될 수 있다. 경구투여를 위한 액상 제제로는 현탁제, 내용액제, 유제, 시럽제 등이 해당되는데, 일반적으로 사용되는 희석제인 물, 리퀴드 파라핀 이외에 여러 가지 부형제, 예를 들면 습윤제, 감미제, 방향제, 보존제 등이 포함될 수 있다. 비경구 투여를 위한 제제에는 멸균된 수용액, 비수용성용제, 현탁제, 유제, 동결건조 제제 및 좌제가 포함된다. 비수용성용제, 현탁제로는 프로필렌 글리콜, 폴리에틸렌 글리콜, 올리브유와 같은 식물성 기름, 에틸올레이트와 같은 주사 가능한 에스테르 등이 사용될 수 있다. 좌제의 기제로는 위텝솔(witepsol), 트윈(tween) 61, 카카오지, 라우린지, 글리세로젤라틴 등이 사용될 수 있다.When formulated, it may be prepared using diluents or excipients such as commonly used fillers, extenders, binders, wetting agents, disintegrants, and surfactants. Solid preparations for oral administration include tablets, pills, powders, granules, capsules, etc., and such solid preparations contain at least one or more excipients such as starch, calcium carbonate, sucrose, lactose, and gelatin in addition to active ingredients. It can be prepared by mixing etc. In addition to simple excipients, lubricants such as magnesium stearate and talc may also be used. Liquid preparations for oral administration include suspensions, solutions for oral administration, emulsions, syrups, etc. In addition to commonly used diluents such as water and liquid paraffin, various excipients such as wetting agents, sweeteners, aromatics, and preservatives may be included. can Formulations for parenteral administration include sterilized aqueous solutions, non-aqueous solvents, suspensions, emulsions, freeze-dried formulations and suppositories. Propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate may be used as non-aqueous solvents and suspending agents. As a base for suppositories, witepsol, tween 61, cacao paper, laurin paper, glycerogelatin, and the like may be used.
본 발명에 따른 약학 조성물은 개체에 다양한 경로로 투여될 수 있다. 투여의 모든 방식이 예상될 수 있는데, 예를 들면 경구, 정맥, 근육, 피하, 복강내 주사에 의해 투여될 수 있다.The pharmaceutical composition according to the present invention can be administered to a subject by various routes. All modes of administration are contemplated, eg oral, intravenous, intramuscular, subcutaneous, intraperitoneal injection.
본 발명에 따른 약학 조성물의 투여량은 개체의 연령, 체중, 성별, 신체 상태 등을 고려하여 선택된다. 상기 약학 조성물 중 포함되는 유효성분의 농도는 대상에 따라 다양하게 선택할 수 있음은 자명하며, 바람직하게는 약학 조성물에 0.01 ~ 5,000 ㎍/ml의 농도로 포함되는 것이다. 그 농도가 0.01 ㎍/ml 미만일 경우에는 약학 활성이 나타나지 않을 수 있고, 5,000 ㎍/ml를 초과할 경우에는 인체에 독성을 나타낼 수 있다.The dosage of the pharmaceutical composition according to the present invention is selected in consideration of the age, weight, sex, and physical condition of the subject. It is obvious that the concentration of the active ingredient included in the pharmaceutical composition can be variously selected according to the subject, and is preferably included in the pharmaceutical composition at a concentration of 0.01 to 5,000 μg/ml. If the concentration is less than 0.01 μg/ml, pharmacological activity may not appear, and if the concentration exceeds 5,000 μg/ml, toxicity to the human body may be exhibited.
상기 약학 조성물은 다양한 경구 또는 비경구 투여 형태로 제형화될 수 있다.The pharmaceutical composition may be formulated into various oral or parenteral dosage forms.
경구 투여용 제형으로는 예를 들면 정제, 환제, 경질, 연질 캅셀제, 액제, 현탁제, 유화제, 시럽제, 과립제 등이 있는데, 이들 제형은 유효성분 이외에 희석제(예: 락토즈, 덱스트로즈, 수크로즈, 만니톨, 솔비톨, 셀룰로즈 및/또는 글리신), 활택제(예: 실리카, 탈크, 스테아르산 및 그의 마그네슘 또는 칼슘염 및/ 또는 폴리에틸렌 글리콜)를 추가로 포함할 수 있다. 또한, 상기 정제는 마그네슘 알루미늄 실리케이트, 전분 페이스트, 젤라틴, 트라가칸스, 메틸셀룰로즈, 나트륨 카복시메틸셀룰로즈 및/또는 폴리비닐피롤리딘과 같은 결합제를 함유할 수 있으며, 경우에 따라 전분, 한천, 알긴산 또는 그의 나트륨 염과 같은 붕해제 또는 비등 혼합물 및/또는 흡수제, 착색제, 향미제 및 감미제를 함유할 수 있다. 상기 제형은 통상적인 혼합, 과립화 또는 코팅 방법에 의해 제조될 수 있다.Formulations for oral administration include, for example, tablets, pills, hard and soft capsules, solutions, suspensions, emulsifiers, syrups, granules, etc. chlorose, mannitol, sorbitol, cellulose and/or glycine), lubricants such as silica, talc, stearic acid and magnesium or calcium salts thereof and/or polyethylene glycol. In addition, the tablet may contain a binder such as magnesium aluminum silicate, starch paste, gelatin, tragacanth, methylcellulose, sodium carboxymethylcellulose and/or polyvinylpyrrolidine, and in some cases starch, agar, alginic acid or a disintegrant or effervescent mixture, such as its sodium salt, and/or absorbents, colorants, flavors, and sweeteners. The formulation may be prepared by conventional mixing, granulating or coating methods.
또한, 비경구 투여용 제형의 대표적인 것은 주사용 제제이며, 주사용 제제의 용매로서 물, 링거액, 등장성 생리식염수 또는 현탁액을 들 수 있다. 상기 주사용 제제의 멸균 고정 오일은 용매 또는 현탁 매질로서 사용할 수있으며 모노-, 디-글리세라이드를 포함하여 어떠한 무자극성 고정오일도 이러한 목적으로 사용될 수 있다.In addition, a typical formulation for parenteral administration is an injection formulation, and water, Ringer's solution, isotonic physiological saline or suspension may be used as a solvent for the injection formulation. Sterile fixed oils of the above injectable preparations may be used as a solvent or suspending medium, and any bland fixed oil may be used for this purpose, including mono- and di-glycerides.
또한, 상기 주사용 제제는 올레산과 같은 지방산을 사용할 수 있다.In addition, the formulation for injection may use a fatty acid such as oleic acid.
본 발명은 곰취(Ligularia fischeri) 추출물 또는 이의 분획물을 유효성분으로 포함하는 당뇨 예방 또는 개선용 의약외품 조성물을 제공할 수 있다.The present invention may provide a quasi-drug composition for preventing or improving diabetes comprising an extract of Ligularia fischeri or a fraction thereof as an active ingredient.
또한, 본 발명은 곰취(Ligularia fischeri) 클로로프롬 분획물을 유효성분으로 포함하는 당뇨 예방 또는 개선용 식품 조성물을 제공할 수 있다.In addition, the present invention can provide a food composition for prevention or improvement of diabetes comprising a chloroform fraction of Ligularia fischeri as an active ingredient.
본 발명의 식품 조성물은 유효성분을 함유하는 것 외에 통상의 식품 조성물과 같이 여러 가지 향미제 또는 천연 탄수화물 등을 추가 성분으로서 함유할 수 있다.In addition to containing the active ingredient, the food composition of the present invention may contain various flavoring agents or natural carbohydrates as additional ingredients like conventional food compositions.
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 향미제는 천연 향미제 (타우마틴), 스테비아 추출물(예를 들어 레바우디오시드 A, 글리시르히진 등) 및 합성 향미제 (사카린, 아스파르탐 등)를 유리하게 사용할 수 있다. 본 발명의 식품 조성물은 상기 약학적 조성물과 동일한 방식으로 제제화되어 기능성 식품으로 이용하거나, 각종 식품에 첨가할 수 있다. 본 발명의 조성물을 첨가할 수 있는 식품으로는 예를 들어, 음료류, 육류, 초코렛, 식품류, 과자류, 피자, 라면, 기타 면류, 껌류, 사탕류, 아이스크림류, 알코올 음료류, 비타민 복합제 및 건강보조식품류 등이 있다.Examples of the aforementioned natural carbohydrates include monosaccharides such as glucose, fructose, and the like; disaccharides such as maltose, sucrose and the like; and polysaccharides such as conventional sugars such as dextrins and cyclodextrins, and sugar alcohols such as xylitol, sorbitol and erythritol. As the flavoring agents described above, natural flavoring agents (thaumatin), stevia extracts (eg rebaudioside A, glycyrrhizin, etc.) and synthetic flavoring agents (saccharin, aspartame, etc.) can advantageously be used. The food composition of the present invention can be formulated in the same way as the pharmaceutical composition and used as a functional food or added to various foods. Foods to which the composition of the present invention can be added include, for example, beverages, meat, chocolate, foods, confectionery, pizza, ramen, other noodles, gum, candy, ice cream, alcoholic beverages, vitamin complexes and health supplements, etc. there is
또한 상기 식품 조성물은 유효성분인 추출물 외에 여러 가지 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, 탄산음료에 사용되는 탄산화제 등을 함유할 수 있다. 그밖에 본 발명의 식품 조성물은 천연 과일 쥬스 및 과일 쥬스 음료 및 야채 음료의 제조를 위한 과육을 함유할 수 있다.In addition, the food composition, in addition to the active ingredient extract, various nutrients, vitamins, minerals (electrolytes), flavors such as synthetic flavors and natural flavors, colorants and enhancers (cheese, chocolate, etc.), pectic acid and its salts, Alginic acid and its salts, organic acids, protective colloidal thickeners, pH adjusting agents, stabilizers, preservatives, glycerin, alcohol, carbonating agents used in carbonated beverages, and the like may be contained. In addition, the food composition of the present invention may contain fruit flesh for preparing natural fruit juice, fruit juice beverages, and vegetable beverages.
본 발명의 기능성 식품 조성물은, 정제,캅셀, 분말, 과립, 액상, 환 등의 형태로 제조 및 가공될 수 있다. 본 발명에서 '건강기능성 식품 조성물'이라 함은 건강기능식품에 관한 법률 제6727호에 따른 인체에 유용한 기능성을 가진 원료나 성분을 사용하여 제조 및 가공한 식품을 말하며, 인체의 구조 및 기능에 대하여 영양소를 조절하거나 생리학적 작용 등과 같은 보건용도에 유용한 효과를 얻을 목적으로 섭취하는 것을 의미한다. 본 발명의 건강기능식품은 통상의 식품 첨가물을 포함할 수 있으며, 식품 첨가물로서의 적합 여부는 다른 규정이 없는 한, 식품의약품안전청에 승인된 식품 첨가물 공전의 총칙 및 일반시험법 등에 따라 해당 품목에 관한 규격 및 기준에 의하여 판정한다. 상기 '식품 첨가물 공전'에 수재된 품목으로는 예를 들어, 케톤류, 글리신, 구연산칼슘, 니코틴산, 계피산 등의 화학적 합성물; 감색소, 감초추출물, 결정셀룰로오스, 고량색소, 구아검 등의 천연첨가물; L-글루타민산나트륨 제제, 면류첨가알칼리제, 보존료 제제, 타르색소제제 등의 혼합제제류 등을 들 수 있다. 예를 들어, 정제 형태의 건강기능식품은 본 발명의 유효성분을 부형제, 결합제, 붕해제 및 다른 첨가제와 혼합한 혼합물을 통상의 방법으로 과립화한 다음, 활택제 등을 넣어 압축성형하거나, 상기 혼합물을 직접 압축 성형할 수 있다. 또한 상기 정제 형태의 건강기능식품은 필요에 따라 교미제 등을 함유할 수도 있다. 캅셀 형태의 건강기능식품 중 경질 캅셀제는 통상의 경질 캅셀에 본 발명의 유효성분을 부형제 등의 첨가제와 혼합한 혼합물을 충진하여 제조할 수 있으며, 연질 캅셀제는 본 발명의 유효성분을 부형제 등의 첨가제와 혼합한 혼합물을 젤라틴과 같은 캅셀기제에 충진하여 제조할 수 있다. 상기 연질 캅셀제는 필요에 따라 글리세린 또는 소르비톨 등의 가소제, 착색제, 보존제 등을 함유할 수 있다. 환 형태의 건강기능식품은 본 발명의 유효성분과 부형제, 결합제, 붕해제 등을 혼합한 혼합물을 기존에 공지된 방법으로 성형하여 조제할 수 있으며, 필요에 따라 백당이나 다른 제피제로 제피할 수 있으며, 또는 전분, 탈크와 같은 물질로 표면을 코팅할 수도 있다. 과립 형태의 건강기능식품은 본 발명의 유효성분의 부형제, 결합제, 붕해제 등을 혼합한 혼합물을 기존에 공지된 방법으로 입상으로 제조할 수 있으며, 필요에 따라 착향제, 교미제 등을 함유할 수 있다.The functional food composition of the present invention may be prepared and processed in the form of tablets, capsules, powders, granules, liquids, pills, and the like. In the present invention, 'health functional food composition' refers to a food manufactured and processed using raw materials or ingredients having useful functionality for the human body according to Health Functional Food Act No. 6727, and the structure and function of the human body It refers to intake for the purpose of obtaining useful effects for health purposes such as regulating nutrients or physiological functions. The health functional food of the present invention may contain ordinary food additives, and the suitability as a food additive is determined according to the general rules of the Food Additive Code and General Test Methods approved by the Food and Drug Administration, unless otherwise specified. It is judged according to standards and standards. Examples of the items listed in the 'Food Additive Code' include, for example, chemical compounds such as ketones, glycine, calcium citrate, nicotinic acid, and cinnamic acid; natural additives such as persimmon pigment, licorice extract, crystalline cellulose, kaoliang pigment, and guar gum; and mixed preparations such as sodium L-glutamate preparations, noodle-added alkali preparations, preservative preparations, and tar color preparations. For example, a health functional food in the form of a tablet is obtained by granulating a mixture obtained by mixing the active ingredient of the present invention with an excipient, a binder, a disintegrant, and other additives in a conventional manner, and then adding a lubricant or the like to compression molding, or as described above. The mixture can be directly compression molded. In addition, the health functional food in the form of a tablet may contain a flavoring agent and the like as needed. Among health functional foods in the form of capsules, hard capsules can be prepared by filling a mixture in which the active ingredient of the present invention is mixed with additives such as excipients in a normal hard capsule. It can be prepared by filling the mixture mixed with gelatin in a capsule base. The soft capsule may contain a plasticizer such as glycerin or sorbitol, a colorant, a preservative, and the like, if necessary. The health functional food in the form of a pill can be prepared by molding a mixture of the active ingredient of the present invention mixed with an excipient, a binder, a disintegrant, etc. by a conventionally known method, and can be coated with sucrose or other coating agent if necessary, Alternatively, the surface may be coated with a material such as starch or talc. Health functional food in the form of granules can be prepared in granular form by a conventionally known method of mixing the active ingredient of the present invention with excipients, binders, disintegrants, etc., and, if necessary, flavoring agents, flavoring agents, etc. can
이하 본 발명을 실시예에 의하여 더욱 상세하게 설명한다. 이들 실시예는 단지 본 발명을 보다 구체적으로 설명하기 위한 것으로, 본 발명의 범위가 이들 실시예에 국한되지 않는다는 것은 당업계에서 통상의 지식을 가진 자에게 있어서 자명할 것이다.Hereinafter, the present invention will be described in more detail by examples. These examples are merely for explaining the present invention in more detail, and it will be apparent to those skilled in the art that the scope of the present invention is not limited to these examples.
<실시예 1><Example 1>
본 발명의 곰취 추출물 제조Preparation of bear odor extract of the present invention
곰취 지상부(2018년 강원도 평창군 수확)를 동결건조기 (PVTFD 50R, Ilshinbio, Seoul, KOREA)에서 건조하여 분말화 하였다. 추출을 위해 건조된 곰취 지상부 50 g을 70% 주정(v/v)(시료와 용매비율 1:10)로 실온에서 24 시간 동안 3번 반복 추출하였다. 추출용액은 여과해서 농축하고 동결 건조하였다. 각 추출물은 100 mg/mL의 농도로 디메틸설폭시드(Dimethylsulfoxide, DMSO, Sigma-Aldrich, St. Louis, MO, USA)에 녹여 희석하여 사용하였다.The above-ground parts of bear sting (harvested in Pyeongchang-gun, Gangwon-do in 2018) were dried in a freeze dryer (PVTFD 50R, Ilshinbio, Seoul, KOREA) and powdered. For extraction, 50 g of dried aerial parts of bear stinger were repeatedly extracted with 70% alcohol (v/v) (1:10 ratio of sample to solvent) at room temperature for 24 hours for 3 times. The extract solution was concentrated by filtration and freeze-dried. Each extract was dissolved in dimethylsulfoxide (DMSO, Sigma-Aldrich, St. Louis, MO, USA) at a concentration of 100 mg/mL and diluted before use.
<실시예 2><Example 2>
본 발명 곰취 분획물 제조 방법Method for producing bear odor fraction of the present invention
곰취 추출물의 순차적 용매 분획은 70% 주정 추출물 1 g을 물 200 mL에 재 용해한 후 분획깔데기 (separatory funnel)에 넣고 헥산(hexane), 클로로포름(chloroform), 에틸 아세테이트(ethyl acetate), 물표준 n-부탄올(water standard n-butanol)의 순서로 가하여 분획하였다. 분획 후 남은 물층을 포함하여 5개의 분획물은 감압농축 후 디메틸설폭시드(DMSO)에 재 용해하여 시료로 사용하였다. 각 용매별 수율은 n-부탄올(n-butanol) 16.0%, 헥산(hexane) 2.0%, 클로로포름(chloroform) 3.0%, 에틸 아세테이트(ethyl acetate) 4.0%, 물 64.0%로 확인되었다.(도 1 참조)For the sequential solvent fractionation of bear stinger extract, 1 g of 70% alcohol extract was re-dissolved in 200 mL of water, put into a separatory funnel, and hexane, chloroform, ethyl acetate, and water standard n- Butanol (water standard n-butanol) was added in order to fractionate. Five fractions, including the water layer remaining after fractionation, were concentrated under reduced pressure, re-dissolved in dimethyl sulfoxide (DMSO), and used as samples. The yield of each solvent was confirmed as 16.0% of n-butanol, 2.0% of hexane, 3.0% of chloroform, 4.0% of ethyl acetate, and 64.0% of water (see FIG. 1). )
<실시예 3><Example 3>
본 발명의 곰취 에탄올 추출물의 클로로포름 분획물의 알파-글루코시다제 억제 효과 확인Confirmation of Alpha-Glucosidase Inhibitory Effect of the Chloroform Fraction of the Ethanol Extract of Gomchidae of the Present Invention
본 발명 곰취 분획물의 알파-글루코시다제(α-glucosidase) 억제 효과를 평가하기 위하여 알파-글루코시다제(α-glucosidase) 활성 비색 분석 키트(biovision, Milpitas,CA, USA)를 이용하였다. 1/10으로 희석한 Sample을 각 well에 10ul씩 넣고, 분석 완충액을 60ul을 첨가 후 10ul의 알파-글루코시다제(α-glucosidase)를 첨가하여 실온에서 빛을 차단하여 30분간 반응시켰다. 그 후 20ul 알파-글루코시다제(α-glucosidase) 기질 혼합물을 각 well에 첨가한 후 microplate reader(Biotek, Winooski, VT, USA)로 410nm에서 40분간 키넥트 모드(kminetic mode)로 흡광도를 측정하였다. In order to evaluate the α-glucosidase inhibitory effect of the bear odor fraction of the present invention, an α-glucosidase activity colorimetric assay kit (biovision, Milpitas, CA, USA) was used. 10ul of the sample diluted by 1/10 was added to each well, 60ul of the assay buffer was added, and 10ul of alpha-glucosidase was added, followed by reaction at room temperature by blocking light for 30 minutes. Then, 20ul alpha-glucosidase (α-glucosidase) substrate mixture was added to each well, and then the absorbance was measured in a kinetic mode at 410 nm for 40 minutes with a microplate reader (Biotek, Winooski, VT, USA). .
이의 결과, 곰취 분획물의 헥산, 클로로포름, 에틸 아세테이트, 부탄올을 이용하여 분획한 분획물들의 알파-글루코시다제(α-glucosidase) 활성 저해효과를 측정하였을때, 곰취 클로로포름 분획물의 활성이 가장 우수하였으며 양성대조군인 아카보즈(acarbose)보다도 저해율이 가장 높음을 확인하였다(도 2 참조).As a result, when the α-glucosidase activity inhibitory effect of the fractions fractionated using hexane, chloroform, ethyl acetate, and butanol of the bear odor fraction was measured, the activity of the bear odor chloroform fraction was the highest and the positive control group It was confirmed that the inhibition rate was the highest than that of acarbose (see FIG. 2).
이제까지 본 발명에 대하여 그 바람직한 실시예들을 중심으로 살펴보았다. 본 발명이 속하는 기술 분야에서 통상의 지식을 가진 자는 본 발명이 본 발명의 본질적인 특성에서 벗어나지 않는 범위에서 변형된 형태로 구현될 수 있음을 이해할 수 있을 것이다. 그러므로 개시된 실시예들은 한정적인 관점이 아니라 설명적인 관점에서 고려되어야 한다. 본 발명의 범위는 전술한 설명이 아니라 특허청구범위에 나타나 있으며, 그와 동등한 범위 내에 있는 모든 차이점은 본 발명에 포함된 것으로 해석되어야 할 것이다.So far, the present invention has been looked at with respect to its preferred embodiments. Those skilled in the art to which the present invention pertains will be able to understand that the present invention can be implemented in a modified form without departing from the essential characteristics of the present invention. Therefore, the disclosed embodiments should be considered from an illustrative rather than a limiting point of view. The scope of the present invention is shown in the claims rather than the foregoing description, and all differences within the equivalent scope will be construed as being included in the present invention.
Claims (12)
상기 곰취 지상부 클로로포름 분획물은 곰취의 지상부를 70%에탄올로 추출한 후, 클로로포름으로 분획한 것인, 조성물.A food composition for the prevention and improvement of diabetes comprising a chloroform fraction of the aerial part of bear odor as an active ingredient,
The chloroform fraction of the aerial part of the bear stink is obtained by extracting the aerial part of the bear stink with 70% ethanol and then fractionating it with chloroform.
상기 추출은 곰취와 용매를 1:10의 부피비로 추출하는 것인, 조성물.According to claim 1,
Wherein the extraction is to extract bear odor and the solvent at a volume ratio of 1:10.
상기 분획물은 알파-글루코시다제(α-glucosidase) 활성 억제하는 것인, 조성물According to claim 1,
Wherein the fraction inhibits alpha-glucosidase activity, composition
상기 곰취 지상부 클로로포름 분획물은 곰취의 지상부를 70%에탄올로 추출한 후, 클로로포름으로 분획한 것인, 조성물.A pharmaceutical composition for inhibiting α-glucosidase activity in the prevention, improvement or treatment of diabetes, comprising a chloroform fraction of the aerial parts of bear stink bug as an active ingredient,
The chloroform fraction of the aerial part of the bear stink is obtained by extracting the aerial part of the bear stink with 70% ethanol and then fractionating it with chloroform.
상기 곰취 지상부 클로로포름 분획물은 곰취의 지상부를 70%에탄올로 추출한 후, 클로로포름으로 분획한 것인, 조성물.A pharmaceutical composition for the prevention or treatment of diabetes comprising a chloroform fraction of the aerial part of bear odor as an active ingredient,
The chloroform fraction of the aerial part of the bear stink is obtained by extracting the aerial part of the bear stink with 70% ethanol and then fractionating it with chloroform.
상기 곰취 지상부 클로로포름 분획물은 곰취의 지상부를 70%에탄올로 추출한 후, 클로로포름으로 분획한 것인, 방법.A method for inhibiting alpha-glucosidase activity, comprising treating a sample with a chloroform fraction of the aerial part of bear stinger in a test tube,
The chloroform fraction of the aerial part of the bear stink is obtained by extracting the aerial part of the bear stink with 70% ethanol and then fractionating it with chloroform.
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박상현 외 7인. PC12 신경세포에서 고당 및 과산화수소로 유도된 산화적 스트레스에 대한 곰취 추출물의 효과. 한국식품과학회지. Vol. 48, No. 5, pp. 508~514(2016) |
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