KR100315001B1 - Herbal Medicine for the Treatment of Diabetes Mellitus Containing Enteric Bellflower Extract - Google Patents
Herbal Medicine for the Treatment of Diabetes Mellitus Containing Enteric Bellflower Extract Download PDFInfo
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- KR100315001B1 KR100315001B1 KR1019980026635A KR19980026635A KR100315001B1 KR 100315001 B1 KR100315001 B1 KR 100315001B1 KR 1019980026635 A KR1019980026635 A KR 1019980026635A KR 19980026635 A KR19980026635 A KR 19980026635A KR 100315001 B1 KR100315001 B1 KR 100315001B1
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- South Korea
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- bellflower
- extract
- jangsaeng
- herbal
- herbal medicine
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- DJPJACADAIGMKF-CTELNEMLSA-N polygalacin-D Natural products O=C(O[C@H]1[C@@H](O[C@H]2[C@H](O)[C@@H](O)[C@@H](O[C@H]3[C@H](O)[C@@H](O[C@@]4(O)[C@H](O)[C@@](O)(CO)CO4)[C@H](O)CO3)[C@H](C)O2)[C@@H](O)[C@@H](O)CO1)[C@@]12[C@H](O)C[C@@]3(C)[C@@]4(C)[C@@H]([C@]5(C)[C@H]([C@@](CO)(C)[C@@H](O[C@H]6[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O6)[C@@H](O)C5)CC4)CC=C3[C@@H]1CC(C)(C)CC2 DJPJACADAIGMKF-CTELNEMLSA-N 0.000 description 1
- DSHSDWSTXKYPEQ-UHFFFAOYSA-N polygalacin-D2 Natural products OC1C(O)C(OC2C(C(OC3C(C(O)(CO)CO3)O)C(O)CO2)O)C(C)OC1OC1C(O)C(O)COC1OC(=O)C1(C(CC2(C)C3(C)CCC4C5(CO)C)O)CCC(C)(C)CC1C2=CCC3C4(C)CC(O)C5OC(C1O)OC(CO)C(O)C1OC1OC(CO)C(O)C(O)C1O DSHSDWSTXKYPEQ-UHFFFAOYSA-N 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 210000003240 portal vein Anatomy 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 208000008128 pulmonary tuberculosis Diseases 0.000 description 1
- 238000010298 pulverizing process Methods 0.000 description 1
- 239000001397 quillaja saponaria molina bark Substances 0.000 description 1
- 208000023504 respiratory system disease Diseases 0.000 description 1
- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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)
- A61K36/34—Campanulaceae (Bellflower family)
- A61K36/346—Platycodon
-
- 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
- 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
-
- 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
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
-
- 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
- A23V2200/00—Function of food ingredients
- A23V2200/30—Foods, ingredients or supplements having a functional effect on health
- A23V2200/328—Foods, ingredients or supplements having a functional effect on health having effect on glycaemic control and diabetes
Abstract
본 발명은 다양한 생리활성을 갖고 있는 20년근 이상의 다년생 도라지(이하 ‘장생도라지’)의 열수 및 유기용매 추출물 또는 이들 추출물에 허용가능한 다른 생약재 또는 생약재 추출물을 선택적으로 혼합한 당뇨병 치료제에 관한 것이다. 본 발명의 장생도라지 추출물은 항균활성, 지질대사개선작용, 혈당강하작용, 암세포접착저해활성, 면역증강작용, 항관절염작용 등에 있어서 기존 약제나 2∼4년근의 일반도라지에 비하여 월등한 효과를 가진다.The present invention relates to a therapeutic agent for diabetes mellitus, which selectively mixes hot water and organic solvent extracts of perennial bellflowers (hereinafter, 'Jangsaeng bellflower') having various physiological activities or other herbal or herbal extracts that are acceptable to these extracts. Jangsaeng Bellflower Extract of the present invention has superior effects compared to conventional drugs or general bellflower of 2-4 years old in antimicrobial activity, lipid metabolism improving action, hypoglycemic action, cancer cell adhesion inhibitory activity, immune enhancing action, anti-arthritis effect, etc. .
Description
발명의 분야Field of invention
본 발명은 대한민국 특허 제45791호의 ‘다년생도라지 재배법’에 따라 생산된 20년근 이상의 장생도라지(長桔)의 다양한 약리적 효능에 기초하여 장생도라지 추출물로 제조되는 당뇨병 치료제로서의 용도에 관한 것이다.The present invention relates to the use as a therapeutic agent for diabetes, which is prepared from Jangsaeng Bellflower Extract based on various pharmacological effects of Jangsaeng Bellflower (長 20) over 20 years old produced according to the “perennial bellflower cultivation method” of Korean Patent No. 45791.
발명의 배경Background of the Invention
도라지(길경 Platycodon grandiflourum A. DC)는 배농, 거담, 기관지염, 천식, 소염 등의 호흡기계질환에 사용되어온 생약제로서 도라지가 배합되어 있는 한방 처방은 동의보감에 273건, 방약합편에 49건이 수록되어 있을 정도로 다양한 약리작용을 가지고 있는 것으로 알려져 있다.Bellflower (Gilkyung Platycodon grandiflourum A. DC) is a herbal medicine used for respiratory diseases such as drainage, expectoration, bronchitis, asthma, and anti-inflammatory, which contains 273 herbal medicines and 49 medical medicines. It is known to have a variety of pharmacological action.
도라지의 주요 약리성분은 테르펜계 사포닌(프레티코틴 A, C, D, D6, 폴리갈라신 D, D2등 18종)으로서 뿌리의 약 2%를 차지하고 있다. 동물실험에서 테르펜계 사포닌은 용혈, 국소자극, 진해, 거담작용, 중추신경억제작용(진정, 진통, 해열효과), 급 ·만성 염증에 대한 항염증작용, 항알레르기, 항궤양 및 위액분비억제작용, 혈관을 확장하여 혈압을 낮추는 항콜린작용, 혈당강하작용, 콜레스테롤 대사개선작용등이 있는 것으로 밝혀졌다〔Igarashi, K., Sogoigaku, 3, 1(1951) 및 이은방, 생약학회지, 5, 49(1974)〕. 또한 알파-스피나스테롤, 스티그마스트-7-엔올, 알파-스피나스테롤글루코시드 등과 같은 스테로이드계 화합물과 이눌린, 플레티코디딘, 베튤린과 같은 다당류도 단리되었다.The major pharmacological component of bellflower is terpene-based saponins (prestigotin A, C, D, D 6 , polygalacin D, D 2 and 18 species), accounting for about 2% of the root. In animal experiments, terpene-based saponins are hemolytic, localized, antitussive, expectorant, central nervous inhibitory (sedative, analgesic, antipyretic), anti-inflammatory against acute and chronic inflammation, anti-allergic, anti-ulcer and gastric secretion , Anticholinergic to lower blood pressure by expanding blood vessels, lowering blood sugar, improving cholesterol metabolism [Igarashi, K., Sogoigaku, 3, 1 (1951) and Lee Eun-bang, Journal of Pharmacognosy, 5, 49 (1974 )]. In addition, steroidal compounds such as alpha-spinasterol, stigmas-7-enol, alpha-spinasterol glucoside and the like and polysaccharides such as inulin, platicodidine and betulin were also isolated.
이외에 도라지의 열수 및 에탄올 추출물은 곰팡이의 아프라톡신을 억제하며 〔Hitokoto, H., Morozumi, S., Wake, T., Sakai, S. and Ueno, I., Mycopathologia, 66, 161(1979)〕, 이눌린(inulin) 분획은 식균작용을 가지며 〔Nagao, T., Matsuda, H., Nambo, K, and Kubo, M., Shoyakugaku Zasshi, 40, 367(1986)〕, 과당중합체인 이눌린은 고형암과 복수암에 대한 항종양효능이 있다고 알려져 있다 〔Naga, T., Matsuda, H., Makata, K., Namba and Kubo, M., Shoyakugaku Zasshi, 40, 375(1986)〕.In addition, the hot water and ethanol extract of bellflower inhibits the fungal apratoxin [Hitokoto, H., Morozumi, S., Wake, T., Sakai, S. and Ueno, I., Mycopathologia, 66, 161 (1979) ], The inulin fraction has phagocytosis [Nagao, T., Matsuda, H., Nambo, K, and Kubo, M., Shoyakugaku Zasshi, 40, 367 (1986)], the inulin, a fructose polymer, is a solid cancer It is known to have antitumor efficacy against cancer and ascites (Naga, T., Matsuda, H., Makata, K., Namba and Kubo, M., Shoyakugaku Zasshi, 40, 375 (1986)).
이러한 도라지의 약리적 성질을 이용한 발명으로 일본특허공개 제60-89427호는 도라지의 70% 메탄올 추출물중의 이눌린 분획이 ICR 마우스의 복수암과 고형암에 대한 억제효능이 각각 31∼39%, 32∼44%로 나타났고, 화학요법제인 마이토마이신과 병용투여시 고형암을 61%까지 억제할 수 있을 뿐만 아니라 마이토마이신의 부작용인 체중감소와 백혈구수의 저하를 억제시킬 수 있다고 개시되어 있다. 이러한 도라지의 우수한 항종양 활성으로 인하여 일본특허공개 2-17292l호는 도라지로부터 이눌린을 분리하는 많은 난점을 개선하고자 도라지의 조직 배양물로부터 얻어진 이눌린을 이용하여 Enrlich 복수암 세포주에 투여하여 50%의 종양억제율과 140∼145%의 생명연명율을 얻은 발명의 효과를 개시하고 있다. 일본특허공개 제3-264534호는 알코올흡수 억제물질로서 40% 길경엑기스를 개시하고 있다.According to the invention utilizing the pharmacological properties of the bellflower, Japanese Patent Laid-Open No. 60-89427 discloses that the inulin fraction in 70% methanol extract of bellflower has 31-39% and 32-44, respectively, inhibitory effects against ascites and solid cancers in ICR mice. In combination with the chemotherapeutic drug mitomycin, it is shown that not only can suppress solid cancer by 61% but also suppress the side effects of mitomycin, such as weight loss and white blood cell count. Due to the excellent anti-tumor activity of the bellflower, Japanese Patent Laid-Open No. 2-17292l was administered to Enrlich ascites cancer cell line using inulin obtained from tissue culture of bellflower to improve many difficulties in separating inulin from bellflower. Disclosed are the effects of the invention that result in inhibition rates and life-expansion rates of 140-145%. Japanese Patent Laid-Open No. 3-264534 discloses a 40% long-light extract as an alcohol absorption inhibitor.
현재 한국, 중국, 일본 등에서 도라지가 함유된 한방제제는 30여종이 시판되고 있는데, 오약순기산, 통기환, 순기원 등은 중풍, 관절염 등의 치료제로서, 안심원과 천왕보심단은 고혈압, 뇌질환 등의 치료제로서, 자모연조 엑기스는 기관지염, 폐결핵, 늑막염 등의 치료제로서, 만옥단은 고혈압, 동맥경화, 당뇨병 등의 치료제로서 각각 이용되고 있다. 이외의 도라지를 함유한 한방제제는 천식, 거담, 배농, 진해 등과 같은 기관지 관련 질병에 사용되고 있다.Currently, about 30 kinds of herbal medicines containing bellflower are sold in Korea, China, Japan, etc., and five kinds of herbal medicines such as five-Yam Soon Ki-san, Tong-hwan, and Soon-gi-won are treatments for stroke, arthritis, etc. As a therapeutic agent for, Jamomile extract is used as a therapeutic agent for bronchitis, pulmonary tuberculosis, pleurisy and the like, and manokdan is used as a therapeutic agent for hypertension, arteriosclerosis and diabetes, respectively. Other herbal preparations containing bellflower are used for bronchial diseases such as asthma, expectoration, drainage, and Jinhae.
그러나 지금까지 상기 한방제제와 실험에 사용되어 왔던 도라지는 4∼5년 이상 재배하면 뿌리가 썩어버리기 때문에 2∼4년생 도라지들이었다. 최근 제45791호로 특허된 ‘다년생 도라지 재배방법’에 의하여 생산된 20년근 이상의 다년생 장생도라지는 특허보호 생약재로서 판매용 한방제제로 전혀 사용되지 않고 있다.However, the bellflowers, which have been used in the herbal medicine and experiments until now, were grown for two to four years because the roots decayed when grown for more than four to five years. More than 20 years of perennial Jangsaeng Doraji produced by the method of cultivating perennial bellflower, which was recently patented as No. 45791, is a patent protected herbal medicine and is not used as a herbal medicine for sale.
따라서 본 발명자들은 2∼4년근의 일반도라지에 비하여 장생도라지가 약리작용에 있어서 현저히 우수한 점을 이용하여 이를 건강보조식품 및 한방제제 등의 약제로서의 용도를 개발하기에 이르렀다.Therefore, the present inventors have developed the use as a medicinal supplement such as health supplements and herbal medicines by utilizing the fact that Jangsaeng Bellflower is significantly superior in pharmacological action compared to the common bellflower of 2-4 years old.
본 발명의 목적은 2∼4년근의 일반도라지에 비하여 우수한 약리작용과 생리활성효능을 가지는 장생도라지의 한방제제로서의 용도를 제공하기 위한 것이다.An object of the present invention is to provide the use as a herbal medicine of Jang Saeng Doraji having excellent pharmacological action and physiological activity compared to the common bellflower of 2-4 years old.
본 발명의 다른 목적은 장생도라지 추출물을 이용한 항균제를 제공하기 위한 것이다.Another object of the present invention is to provide an antimicrobial agent using Jangsaeng Bellflower Extract.
본 발명의 또 다른 목적은 생체내에서 독성이 없으며 다른 부작용이 없는 한방제제를 제공하기 위한 것이다.It is another object of the present invention to provide an herbal preparation that is nontoxic in vivo and has no other side effects.
본 발명의 상기 목적 및 기타의 목적들은 하기 설명되는 본 발명에 의하여 모두 달성될 수 있다.The above and other objects of the present invention can be achieved by the present invention described below.
본 발명은 장생도라지를 분말로 제조한 다음, 이를 열수추출하거나 유기용매를 이용하여 추출하여 제조된 추출액을 혈당강하제 또는 당뇨병 치료제로 사용하는 용도에 관한 발명이다. 하기에서는 일반도라지와 장생도라지의 구성물질 및 약리작용의 차이에 대하여 상세히 살펴본다.The present invention relates to the use of an extract prepared by preparing Jangsaeng Doraji as a powder and then extracting it using hot water extraction or an organic solvent as a hypoglycemic agent or a diabetic agent. In the following, the difference between the constituents and pharmacological action of the common bellflower and Jangsaeng bellflower will be examined in detail.
일반도라지와 장생도라지는 일반 성분중 수분, 조지방, 무기염 등에 있어서 큰 차이가 없다. 식이섬유의 총량 및 조사포닌 양은 22년근에서 각각 3.1% 및 0.4%로 높게 검출된다. 도라지의 구성 당성분중 이눌린의 총함량은 70∼73 mg/g으로 거의 변화가 없었으나 이눌린의 구성 당성분인 프락토스(fluctose)의 중합도에 큰 차이가 있다. 즉 장생도라지에서는 G-F2와 G-F3의 함량이 높고 일반도라지에서는 G-F5에서 G-F8의 함량이 상대적으로 높게 나타나 이눌린의 구조에 상당한 차이가 있슴이 밝혀졌다. 상기에서 G는 글루코스이고, F는 프락토스로서 이눌린의 구성성분을 나타낸 것이며 숫자는 프락토스의 개수를 나타낸 것이다. 이와 같이 이눌린의 과당중합도는 도라지의 재배년수가 증가할수록 과당수가 작은 올리고프락토스가 높게 검출된다. 이러한 결과는 일반도라지에 비하여 장생도라지가 고혈압, 기관지,당뇨병 등에 효능이 우수한 임상실험 결과와 관련이 있는 것으로 추측된다.Common Bellflower and Jangsaeng Bellflower have no big difference in moisture, crude fat, mineral salt, etc. among common ingredients. The total amount of dietary fiber and the amount of irradiated phononine were detected as high as 3.1% and 0.4% at 22 years old, respectively. The total content of inulin in the constituent sugar components of the bellflower was almost unchanged from 70 to 73 mg / g, but there was a big difference in the degree of polymerization of fructose, the constituent sugar component of inulin. I.e. the higher the content of the Jang Saeng Doraji GF 2 and GF 3 shows the content of the general bellflower GF 8 relatively higher in GF 5 has been found that if asked a significant difference in the structure of inulin. In the above, G is glucose, F is fructose, which represents a component of inulin, and the number represents the number of fructose. As such, the fructose degree of fructose is detected with higher oligofractose with a lower fructose as the number of years of cultivation increases. These results are inferred to be related to the results of clinical trials that Jangsaeng Bellflower is superior to hypertension, bronchus, diabetes, etc.
무기염으로서 칼슘(Ca), 마그네슘(Mg), 구리(Cu)의 함량이 일반도라지에 비하여 장생도라지에서 3∼10배 높게 검출된다.As inorganic salts, the contents of calcium (Ca), magnesium (Mg), and copper (Cu) are detected 3 to 10 times higher in Jangsaeng Bellflower than the common bellflower.
일반도라지와 장생도라지를 80% 에탄올과 30% 메탄올로 추출하여 HPLC로 분석하여 보면 각각 한 개와 두 개의 피크가 함량의 차이가 나타난다. 장생도라지에만 많이 존재하는 이 피크를 다시 극성도에 따라 용매로 분획하여 생리활성을 조사한 결과 석유에테르와 디에틸에테르 분획물에서 효과가 인정되어 여러 기기분석을 통하여 구조분석하였을 때 스테로이드계 물질임이 판명되었다 〔하시봉, 석사학위논문, 경상대학교 (1996)〕.General and Jangsaeng bellflowers were extracted with 80% ethanol and 30% methanol, and analyzed by HPLC. The peaks, which are present only in Jangsaeng Doraji, were divided into solvents according to their polarity, and their physiological activities were examined. The effects were recognized in the petroleum ether and diethyl ether fractions. [Hashibong, Master Thesis, Gyeongsang National University (1996)].
장생도라지는 일반도라지와 구성성분에 있어서 상당한 차이가 있을 뿐만 아니라 항균활성, 지방대사개선작용, 암세포접착저해활성, 면역증강작용, 형당강하작용, 혈당강하작용 등의 약리적효능에 있어서도 일반도라지에 비하여 월등히 우수하다.Jangsaeng Doraji not only has a significant difference in the composition and composition, but also in pharmacological effects such as antibacterial activity, fat metabolism improvement, cancer cell adhesion inhibitory activity, immunopotentiation, hypoglycemic action, hypoglycemic action, etc. Excellent
장생도라지의 80% 에탄올과 30% 메탄올추출물은 자유라디칼 소거작용과 항진균작용이 있으며 세포독성이 없다. 장생도라지는 일반도라지에 비하여 광범위하고 우수한 항균스펙트럼을 보인다. 장생도라지의 에탄올 추출물은 세균에 대해서는 5 mg/ml, 진균류에 대해서는 2.5∼10 mg/ml 농도의 최소저해농도(MIC) 값을 나타낸다. 항균활성물질은 50℃, 95% 에탄올 농도에서 가장 용이하게 추출된다. 장생도라지의 95% 에탄올 추출물을 다시 용매로 분획하였을 때 부탄올 분획에서 항균활성이 가장 높은 것으로 나타나는데 이것은 사포닌 성분에 기인되는 것으로 추측되고,다른 용매분획에서도 활성이 검출되는 것을 보아 항균활성물질이 2개 이상인 것으로 추론된다. 장생도라지의 항균활성물질들 중에 에틸아세테이트 분획물에서 분리되어 여러 기기를 사용하여 구조분석을 한 결과 글리세릴 리놀레이트임이 규명되었다.80% ethanol and 30% methanol extract of Jangsaeng Doraji has free radical scavenging and antifungal activity and no cytotoxicity. Jangsaeng Bellflower shows broader and superior antibacterial spectrum than the common bellflower. Ethanol extract of Jangsaeng Doraji has a minimum inhibitory concentration (MIC) value of 5 mg / ml for bacteria and 2.5-10 mg / ml for fungi. Antimicrobial actives are most easily extracted at 50 ° C. and 95% ethanol concentration. When the 95% ethanol extract of Jangsaeng Doraji was again fractionated with solvents, the butanol fraction showed the highest antimicrobial activity, which is believed to be due to the saponin component, and the activity was detected in other solvent fractions. It is inferred to be abnormal. Among the antimicrobial active substances of Jangsaeng Doraji, it was isolated from ethyl acetate fraction and analyzed by structural analysis using several instruments. It was identified as glyceryl linoleate.
또한 고지혈증 유발쥐에 장생도라지 분말 또는 추출물을 식이시킬 경우 혈청과 간장의 혈당 및 지질함량이 현저하게 감소된다. 특히 장생도라지 분말 5% 식이군에서는 혈청과 간장중의 총콜레스테롤과 중성지질의 농도가 현저히 감소되고 이때 동맥경화지수도 장생도라지로 처리하지 않은 대조군에 비하여 낮게 나타난다. 이런 결과는 고콜레스테롤증 또는 고지혈증 예방 및 치료에 장생도라지의 처방가능성을 제시해 주고 있다.In addition, the blood glucose and lipid content of serum and liver are significantly reduced when dieting Jangsaeng Dorage powder or extract in hyperlipidemic rats. In particular, the 5% diet of Jangsaeng Doraji powder significantly reduced the concentrations of total cholesterol and neutral lipids in serum and liver, and the arteriosclerosis index was also lower than that of the control group that was not treated with Jangsaeng Doraji. These results suggest the possibility of prescribing Jangsaeng Doraji in the prevention and treatment of hypercholesterolemia or hyperlipidemia.
본 발명의 장생도라지 추출물은 혈당, 혈청, 간장 등의 지질개선효과가 일반도라지에 비하여 우수하여 당뇨병 치료에도 유용하다. 장생도라지 추출물은 체내에서 혈청 총콜레스테롤 및 LDL의 농도를 상당한 수준으로 감소시키며 혈청 HDL-콜레스테롤 농도는 증가시키는 작용을 한다. 혈청 유리콜레스테롤, 콜레스테롤 에스테르, 중성지질 및 인지질의 농도 또한 낮은 수준으로 감소시키며 동맥경화지수도 낮아진다.Jangsaeng bellflower extract of the present invention is effective in the treatment of diabetes mellitus is superior to the general bellflower lipids, such as blood sugar, serum, liver. Jangsaeng Doraji extract acts to significantly reduce serum total cholesterol and LDL levels in the body and increase serum HDL-cholesterol levels. Serum free cholesterol, cholesterol esters, triglycerides and phospholipids are also reduced to low levels and atherosclerosis is low.
장생도라지 추출물을 암세포주에 처리하게 되면 암세포접착저해활성이 우수하게 나타난다. 장생도라지 메탄올 추출물을 B16-F1 생쥐 멜라노마 세포에 처리하여 라미닌(laminin)의 결합력을 측정하여 보면 추출물의 농도가 0.125 mg/ml 이상이 되면 암세포주에서 100% 암세포접착저해활성이 나타나게 된다. 이로써 장생도라지 추출물이 암전이를 낮은 농도에서도 저해할 수 있음을 알 수 있다.When Jangsaeng Doraji extract is treated to cancer cell lines, the cancer cell adhesion inhibitory activity is excellent. When Jangsaeng Doraji methanol extract was treated to B16-F1 mouse melanoma cells to measure the binding force of laminin (laminin) when the concentration of the extract is more than 0.125 mg / ml will show 100% cancer cell adhesion inhibitory activity in cancer cell lines. It can be seen that Jangsaeng Doraji extract can inhibit cancer metastasis even at low concentrations.
또한 장생도라지 추출물을 용매의 극성에 따라 분획하여 면역증강기능을 조사하여 보면 수용액층에서 가장 우수한 효과가 나타난다. 이 수용액층을 HPLC 분석한 결과 이눌린의 프락토스 중합도가 20개 이하의 이눌린 분획에서 가장 우수한 면역증강활성이 검출된다. 장생도라지가 일반도라지에 비하여 면역증강활성이 5배이상 높은 결과는 이눌린의 프락토스 중합도와 밀접한 상관성이 있는 것으로 추측된다.In addition, the extract of Jangsaeng Doraji extract according to the polarity of the solvent to investigate the immune enhancing function shows the best effect in the aqueous layer. HPLC analysis of this aqueous layer showed the best immunostimulating activity in the inulin fraction of 20 inulin fructose polymerization. It is estimated that Jangsaeng Doraji correlates with inulin's fructose polymerization.
장생도라지 추출물은 부종의 저해성능이 있으므로 류마티스 관절염과 같은 염증성 질환의 치료에도 사용될 수 있다. 기존의 부종 저해약제인 프레디졸론 (predisolone)에 비등한 부종저해활성을 나타낸다. 장생도라지의 효능을 상승시킬 수 있는 허용가능한 생약재 또는 생약재 추출물을 혼합시키면 상승작용으로 인하여 부종의 억제활성이 더 높아진다.Jangsaeng Doraji extract can be used for the treatment of inflammatory diseases such as rheumatoid arthritis because it has the ability to inhibit edema. It shows edema inhibitory activity similar to that of predisolone, an edema inhibitor. Incorporation of an acceptable herbal medicine or herbal extract that can enhance the efficacy of Jangsaeng Dorage will increase the inhibitory activity of edema due to synergy.
본 발명에서는 이러한 우수한 장생도라지의 약리활성을 이용한 약제를 제공한다. 본 발명의 약제로 제공될 수 있는 장생도라지 추출물은 이 분야에서 통상적으로 사용되는 방법에 따라 제조된다. 장생도라지 추출물은 통상 열수추출물 또는 유기용매추출물을 들 수 있으며 이러한 추출물들은 단독으로 사용될 수도 있으며 생약재를 첨가하여 제조될 수도 있다.The present invention provides a drug using the excellent pharmacological activity of Jangsaeng Doraji. Jangsaeng Doraji extract which can be provided as a medicament of the present invention is prepared according to methods commonly used in the art. Jangsaeng Doraji extract can usually include hot water extract or organic solvent extract, these extracts may be used alone or may be prepared by adding a herbal medicine.
일반적으로 장생도라지 분말은 수분의 함량이 5%이하가 되도록 장생도라지를 건조하고 이를 분쇄한 다음, 입자크기가 0.6mm이하인 것을 선별하여 제조된다. 열수추출물은 장생도라지 분말에 약 5∼10배의 물을 첨가하고 90∼100℃의 온도에서 4∼6시간동안 2회 추출하여 얻은 여과액 에 허용가능한 생약재 또는 생약재 추출물을 선택적으로 첨가하여 제조된다. 유기용매 추출물의 경우에는 장생도라지 분말에 약 3배의 유기용매를 첨가하고 실온에서 2회 추출하여 얻어진 여과액을 감압농축하여 추출물에 허용가능한 생약재 또는 생약재 추출물을 선택적으로 첨가하여 제조된다.Generally, Jangsaeng Bellflower powder is prepared by drying Jangsaeng Bellflower so as to have a moisture content of 5% or less, pulverizing it, and then selecting a particle size of 0.6mm or less. The hot water extract is prepared by adding about 5-10 times of water to Jangsaeng Bellflower powder and selectively adding an acceptable herbal or herbal extract to the filtrate obtained by extracting twice for 4-6 hours at a temperature of 90-100 ° C. . In the case of the organic solvent extract, about three times the organic solvent is added to Jangsaeng Bellflower powder, and the filtrate obtained by extracting twice at room temperature is concentrated under reduced pressure to be prepared by selectively adding an acceptable herbal or herbal extract to the extract.
상기 유기용매로는 알코올이 사용될 수 있으며 메탄올, 에탄올 등이 바람직하게 사용될 수 있다. 허용가능한 생약재로는 창출, 산사자, 원지, 하수오, 백복령, 사상자를 등이 있다.Alcohol may be used as the organic solvent, and methanol, ethanol, or the like may be preferably used. Acceptable herbal medicines include creation, mountain lions, gardens, sewage, baekbokyeong, and casualties.
본 발명의 장생도라지 추출물들은 식품위생법상 또는 약재학적으로 허용가능한 보형제를 이용하는 공지의 방법으로 건강보조식품화 또는 제제화되어 단위 용량 형태 또는 다용량 용기에 내압시킬 수 있다. 건강보조식품 또는 제제형태는 수성액, 현탁액 또는 유화액 형태이거나 엑기스제, 분말제, 과립제, 정제, 캅셀제 형태일 수 있으며, 통상의 분산제, 현탁제 또는 안정화제를 함유할 수 있다.Jangsaeng Doraji extracts of the present invention may be formulated or formulated as a dietary supplement in a known manner using food hygiene or pharmacologically acceptable prostheses and pressurized into unit dosage forms or multi-dose containers. The dietary supplement or formulation may be in the form of an aqueous solution, suspension or emulsion, or may be in the form of extracts, powders, granules, tablets, capsules, and may contain conventional dispersants, suspensions or stabilizers.
본 발명은 하기의 실시예에 의하여 구체화될 것이며, 하기 실시예는 본 발명을 예시하기 위한 것으로, 본 발명의 범위를 제한하고자 하는 것은 아니다.The present invention will be embodied by the following examples, which are intended to illustrate the invention and are not intended to limit the scope of the invention.
실시예Example
실시예 1 : 장생도라지 추출물 한방제제 제조Example 1 Preparation of Jangsaeng Bellflower Extract Herbal Medicine
장생도라지를 수분함량 5% 이하로 건조시켜 분쇄한 다음 입자의 크기가 0.6mm이하 되게 선별하여 분말로 제조한다. 장생도라지 분말에 대하여 10배의 물을 넣어 90-100℃에서 4-6시간동안 2회 추출하고 여과액을 포장하여 액상제품을 제조하였다. 또한 여과액을 더 농축하여 엑기스제, 분말제, 과립제, 캅슐제 및 환형 한방제제를 제조하였다.Jangsaeng bellflower is dried to a moisture content of 5% or less, pulverized, and sorted to a particle size of 0.6 mm or less to prepare a powder. 10 times of water was added to Jangsaeng Bellflower powder and extracted twice at 4-100 hours at 90-100 ° C. to prepare a liquid product. In addition, the filtrate was further concentrated to prepare an extract, powder, granules, capsules and cyclic herbal medicines.
에탄올 추출물은 장생도라지 1kg을 분쇄하여 실온에서 에탄올 4L로 2일간 2회 추출하고 여과액을 모아 감압농축하여 125g의 추출물을 얻었다. 이 추출물을 이용하여 엑기스제, 분말제, 과립제, 캅슐제 및 환형 한방제제를 제조하였다.The ethanol extract was ground 1kg of Jangsaeng Bellflower, extracted twice with 4L of ethanol at room temperature for 2 days, and the filtrate was collected and concentrated under reduced pressure to obtain 125g of extract. The extract was used to prepare extracts, powders, granules, capsules and cyclic herbal medicines.
상기 장생도라지 추출물은 효능을 상승시키고자 창출, 산사자, 원지, 하수오, 백복령, 사상자 등과 같은 허용가능한 생약재 또는 상기와 같은 방법으로 추출, 농축한 생약재 추출물을 첨가하여 제조될 수 있다.The extract of Jangsaeng Doraji may be prepared by adding an acceptable herbal medicine such as creation, mountain lion, raw paper, sewage, baekbokyeong, casualty and the like, or extract and concentrated herbal medicine extract as described above to increase the efficacy.
실시예 2 :Example 2:
장생도라지추출물이 당뇨성 횐쥐의 혈당 및 지질성분에 미치는 영향 Effect of Jangsaeng Bellflower Extract on Blood Glucose and Lipid Components in Diabetic Rats
체중이 70±5g이고 4주일된 Sprague Dawley계 흰쥐에 알록산 모노히드레이 트(l5mg/kg B.W/day)를 복강내 주사(I.P. injection)하여 당뇨병 흰쥐가 되도록 하였다. 실험동물은 난괴법에 따라 6마리씩 A, B, 및 C의 3개 군으로 나누어 3주간 각 실험군의 식이에 따라 자유로이 섭취시켰다. A군에는 일반사료만을 급이하고(대포군), B군은 6년근 도라지 추출물을 혼합시킨 사료를 급이하고, C군은 장생도라지 (22년근) 추출물을 혼합시킨 사료를 급이하였다. 효과를 비교하기 위하여 체중이 70±5g이고 4주일된 정상적인 흰쥐 6마리(D군)에 일반사료를 급이하였다. 실험에 사용된 도라지 추출물은 동결건조된 도라지 200g에 물을 첨가하여 1L로 한 후 700ml로 농축시키고, 그 잔사에 다시 물 800ml을 넣고 300ml가 될 때까지 열수추출하여 제조하였다. 실험사육 3주간의 최종일에는 7시간 질식시킨 후 에테르 마취하에 심장채혈법으로 채혈하였고 간강은 0.9% 생리식염수로 문맥을 통하여 관류 탈혈한 후 여과지로써 물기를 제거하였으며, 혈액은 약 1시간 정도 빙수중에 방치한 후 3,000rpm에서 15분간 원심분리하여 혈청을 얻었다. 상기 혈청과 간장에서의 혈당, 콜레스테롤, 중성지질(트리글리세라이드), 인지질, AST(aspartate aminotransferase), ALT(alanine aminotransferase) 및 LDH(lactate dehydrogenase)를 측정하여, 그 결과는 표1에 기재하였다. 이들 혈당, 콜레스테롤, 지질, 및 효소활성은 이 분야의 통상으로 사용되는 측정용 kit 시약을 이용하여 측정하였다.Four-week-old Sprague Dawley rats weighed 70 ± 5 g were treated with I.P.injection of alloxane monohydrate (l 5 mg / kg B.W / day) to make diabetic rats. Experimental animals were divided into three groups, A, B, and C, six by the egg mass method, and freely ingested according to the diet of each experimental group for three weeks. Group A was fed only general feed (Daepo group), group B was fed feed mixed with 6 years old bellflower extract, and group C was fed feed mixed with Jangsaeng Bellflower (22 years old) extract. To compare the effects, normal diets were fed to 6 normal rats (group D) weighing 70 ± 5 g and 4 weeks old. The bellflower extract used in the experiment was prepared by adding water to 200 g of lyophilized bellflower, making it 1L and concentrating to 700ml. Then, 800ml of water was added to the residue, followed by hot water extraction until it became 300ml. On the last day of 3 weeks of experimental breeding, after choking for 7 hours, blood was collected by cardiac sampling under ether anesthesia. The liver cavity was perfused with 0.9% physiological saline through the portal vein, and then drained by filter paper. Blood was kept in ice water for about 1 hour. After standing, centrifuged at 3,000 rpm for 15 minutes to obtain a serum. Blood glucose, cholesterol, triglyceride (triglyceride), phospholipid, aspartate aminotransferase (AST), alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) in serum and liver were measured, and the results are shown in Table 1. These blood glucose, cholesterol, lipids, and enzyme activity were measured using a kit kit for measurement commonly used in the art.
상기 표 1에 기재된 바와 같이 혈당농도는 알록산 투여군(A, B 및 C군)이 알록산을 투여하지 아니한 D군에 비하여 유의적으로 높았으나 대조군인 A군에 비해서 도라지 추출물로 처리된 B군과 C군이 낮았으며 특히 장생도라지 추출물로 처리된 C군이 가장 낮았다.As shown in Table 1, the blood glucose concentration was significantly higher in the oxalose group (A, B, and C groups) than the D group which did not receive the oxalate, but was treated with bellflower extract compared to the control group A group. And C group were low, especially C group treated with Jangsaeng Doraji extract.
혈청 총콜레스테롤 및 LDL의 농도는 A군에 비해 B군과 C군이 낮았으며, 이중 C군이 더욱 낮아 알록산을 투여하지 않은 D군에 가장 가까운 수치를 나타내었다. 혈청 HDL-콜레스테롤 농도는 A군에 비해 도라지 추출액 급여군(B 및 C군)에서 높게 나타났으며 이중 C군이 더 높은 수치를 가져 알록산을 투여하지 않은 D군에 가장 가까운 것으로 나타났다. 동맥경화지수는 A군에 비해 B군과 C군이 낮았다. 혈청 유리콜레스테롤, 콜레스테롤 에스테르, 중성지질 및 인지질의 농도는 A군에 비해 전 실험군에서 유의적으로 낮았다. 간장중 전체 콜레스테롤, 중성지질 및 인지질의 함량은 A군에 비해 전 실험군에서 유의적으로 낮았다. 혈청 AST, ALT 및 LDH 효소활성은 A군이 가장 높았으며 다른 실험군들은 비교적 낮았다. 이상의 결과에서 도라지 추출액이 혈당, 혈청 및 간장의 지질개선에 효과가 있는 것으로 나타났으며, 특히 장생 도라지 추출액이 더욱 효과적인 것으로 나타났다.Serum total cholesterol and LDL concentrations were lower in group B and C than group A. Among them, group C was lower than group D, which was not treated with alloxan. Serum HDL-cholesterol concentration was higher in the bellflower extract group (B and C) than in group A. Among these groups, group C had higher values, which was closest to group D without administration of alloxan. Atherosclerosis index was lower in group B and C than group A. Serum free cholesterol, cholesterol esters, triglycerides and phospholipids were significantly lower in all experimental groups than in group A. The contents of total cholesterol, triglyceride and phospholipids in liver were significantly lower in all experimental groups than in group A. Serum AST, ALT and LDH enzyme activities were highest in group A and relatively low in other experimental groups. From the above results, the bellflower extract was found to be effective in improving lipids of blood sugar, serum and liver, and especially the Jangsaeng Bellflower extract was more effective.
본 발명의 20년근 이상의 장생도라지 추출물로 제조된 한방제제는 2∼4년근의 일반도라지에 비하여 약리작용과 생리활성효능이 우수하며, 혈청이나 간장에서 혈당강하작용이나 지질대사개선작용에 있어서 일반도라지에 비하여 월등히 우수하다. 본 발명의 장생도라지로 제조된 당뇨병 치료제는 생체내에서 독성이 없으며 다른 부작용이 없는 발명의 효과도 가진다.Herbal preparations made with Jangsaeng Doraji extracts of more than 20 years of the present invention have excellent pharmacological and physiological activities as compared to the general bellflowers of 2-4 years old, and the common bellflower in hypoglycemic activity or lipid metabolism improvement in serum or liver It is much better than that. Diabetes treatment agent prepared with Jang Saeng Doraji of the present invention is non-toxic in vivo and has the effect of the invention without other side effects.
본 발명의 단순한 변형 내지 변경은 이 분야의 통상의 지식을 가진 자에 의하여 용이하게 실시될 수 있으며, 이러한 변형이나 변경은 모두 본 발명의 영역에포함되는 것으로 볼 수 있다.Simple modifications and variations of the present invention can be readily made by those skilled in the art, and all such modifications or changes can be seen to be included in the scope of the present invention.
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KR100446978B1 (en) * | 2002-04-26 | 2004-09-01 | 강원도 | Liquid Type Tea Composition for Dropping Blood Sugar Level Using Volunteer |
KR101778142B1 (en) | 2015-11-26 | 2017-09-13 | 주식회사 장생도라지 | Old Platycodon Composit Composition Enhanced Antidiabetic Activity |
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US6902748B1 (en) * | 1999-12-22 | 2005-06-07 | Jang Saeng Doraji Co., Ltd | Medicines manufactured from old platycodon extracts |
KR100550465B1 (en) * | 2003-07-22 | 2006-02-08 | 정혜광 | old platycodon extracts for prevention angiogenesis associated with growth and metastasis of cancer cells |
KR100541248B1 (en) * | 2003-07-22 | 2006-01-11 | 주식회사 장생도라지 | old platycodon extracts for prevention of cancer metastasis |
KR101333123B1 (en) * | 2011-05-20 | 2013-11-26 | 이혜경 | Preparation Method of Cooking Syrup Comprising Extract of Platycodon grandiflorum |
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KR100446978B1 (en) * | 2002-04-26 | 2004-09-01 | 강원도 | Liquid Type Tea Composition for Dropping Blood Sugar Level Using Volunteer |
KR101778142B1 (en) | 2015-11-26 | 2017-09-13 | 주식회사 장생도라지 | Old Platycodon Composit Composition Enhanced Antidiabetic Activity |
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