KR20020083246A - Ganoderma applanatum extract for the therapy of diabetic diseases - Google Patents

Ganoderma applanatum extract for the therapy of diabetic diseases Download PDF

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KR20020083246A
KR20020083246A KR1020010022643A KR20010022643A KR20020083246A KR 20020083246 A KR20020083246 A KR 20020083246A KR 1020010022643 A KR1020010022643 A KR 1020010022643A KR 20010022643 A KR20010022643 A KR 20010022643A KR 20020083246 A KR20020083246 A KR 20020083246A
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extract
ganoderma applanatum
diabetic
diabetes
present
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KR100416399B1 (en
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이형규
박형섭
양승돈
손달훈
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한국생명공학연구원
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/06Fungi, e.g. yeasts
    • A61K36/07Basidiomycota, e.g. Cryptococcus
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/08Solutions
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/14Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
    • A61K2236/10Preparation or pretreatment of starting material
    • A61K2236/15Preparation or pretreatment of starting material involving mechanical treatment, e.g. chopping up, cutting or grinding
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
    • A61K2236/30Extraction of the material
    • A61K2236/33Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones

Abstract

PURPOSE: The use of a Ganoderma applanatum extract prepared by extraction of Ganoderma applanatum in one organic solvent of lower alcohol, water or acetone as an agent for prevention and treatment of diabetes mellitus is provided. The extract can strongly inhibit weight gain while having excellent an effect on reducing blood sugar levels. CONSTITUTION: Ganoderma applanatum is extracted in lower alcohol, water or acetone and then concentrated under reduced pressure or freeze dried. The effective amount of the Ganoderma applanatum extract is 10 to 1,500mg, preferably 50 to 500mg, and a pharmaceutical composition for prevention and treatment of diabetes mellitus contains the Ganoderma applanatum extract and a pharmaceutically acceptable salt or an excipient and is formulated into an oily or aqueous solution, suspension or emulsion, extract, powder, granule, tablet or capsule.

Description

당뇨질환의 예방 또는 치료용 잔나비불로초버섯 추출물{Ganoderma applanatum extract for the therapy of diabetic diseases}Ganoderma applanatum extract for the therapy of diabetic diseases}

본 발명은 당뇨질환의 예방 또는 치료용 잔나비불로초버섯 추출물에 관한 것으로서, 더욱 상세하게는 잔나비불로초버섯을 저급 알콜, 물, 아세톤 중 어느 하나의 유기용매로 추출하여 얻어지는 본 발명 잔나비불로초버섯 추출물이 갖는 항당뇨질환 물질로서의 용도에 관한 것이다.The present invention relates to an extract of Janna bulbulo vinegar mushroom for the prevention or treatment of diabetic diseases, and more particularly, to the zanabibulo vinegar mushroom extract of the present invention obtained by extracting zanabi bulo vinegar mushroom with any one of an organic solvent of lower alcohol, water or acetone. It relates to the use as an antidiabetic substance.

잔나비불로초버섯은 다년생으로 자루가 없으며 목질화되어 있다. 크기는 6∼60㎝의 넓이에 5∼10㎝의 두께를 가지고 있고, 중앙이 약간 볼록한 반원형이며, 단단한 표면은 회색 또는 밤색을 띤다. 포자는 ㎜당 4∼6개가 있고, 6∼9.5 × 5.7㎛의 타원형 모양이며, 색깔은 흰색 또는 담황색인데 손상을 입으면 담갈색으로변하고 알칼리에 의해 검은색으로 변하며 말리면 담황색으로 변한다. 이 버섯은 활엽수나 침엽수, 예를 들어 자작나무, 단풍나무, 너도밤나무, 홰나무 등에서 기생한다. 이 버섯은 우리나라를 비롯하여 일본, 중국, 캐나다 등 세계적으로 널리 분포한다. 중국에서는 이 버섯을 식도암 치료를 위한 민간약으로 사용한 사실도 있다.Jan Butterfly Bulchocho mushrooms are perennial, without sacks, and woody. The size is 6 ~ 60cm wide, 5 ~ 10cm thick, semiconvex with slightly convex center, and hard surface is gray or brown. Spores 4-6 per mm, 6-9.5 × 5.7㎛ oval-shaped, white or light yellow, when damaged, it turns light brown, black by alkali, and light yellow when dried. The mushrooms are parasitic in hardwoods and conifers, such as birch, maple, beech and beech. This mushroom is widely distributed in Korea, Japan, China and Canada. In China, the mushrooms have been used as a folk medicine for the treatment of esophageal cancer.

본 발명의 잔나비불로초버섯의 성분과 생리활성에 대하여 그 동안의 연구를 살펴보면, 트리테르페노이드(triterpenoid) 성분(T. Nishitoba 등, Phytochemistry 28(1), 193-197 (1989); K.H. Gan 등,J. Nat. Prod.61, 1421-1422 (1998); J. Protiva 등,Coll. Czech. Chem. Comm.45, 2710-2713 (1980)), 트리테르펜(triterpene) 성분의 항암프로모터(anti-tumour promoter) 활성(Chairul 등, Phytochemistry 30(12), 4105-4109 (1991); Phytochemistry 35(5), 1305-1308 (1994)) 등이 보고되었고, 다당체 디-글루칸(D-glucan)의 항암활성(T. Mizuno 등, Bull. Fac. Agr. Shizuoka Univ. 31, 49-64 (1981); T. Usui 등, Carbohydrate Res. 115, 273-280 (1983))과 수용성 물질의 항바이러스 작용(S.K. Eo 등, Arch. Pharm. Res. 24(1), 74-78 (2001))과 면역반응에 대한 효과(Y.S. Kim 등, Kor. J. Pharmacogn. 25(4), 348-355 (1994)) 등이 발표되었다. 그 외에도 잔나비불로초버섯의 물추출물의 항생물질 병용효과(Y.S. Kim 등, Yakhak Hoeji 38(6), 742-748 (1994)), 인터페론 병용효과에 의한 항바이러스 작용(J.H. Kim 등, Yakhak Hoeji 43(4), 464-468 (1999), S.S. Jung 등, Yakhak Hoeji 43(4), 464-468 (1999)) 등도 보고된 바 있다. 그러나, 당뇨질환과 관련한 잔나비불로초버섯의 용도에 대해서는 전혀 보고된 바 없다.Looking at the research of the components and physiological activity of the Xavier bulbucho mushroom of the present invention, triterpenoid component (T. Nishitoba et al., Phytochemistry 28 (1), 193-197 (1989); KH Gan et al. , J. Nat. Prod. 61, 1421-1422 (1998); J. Protiva et al. , Coll. Czech.Chem . Comm. 45, 2710-2713 (1980)), anti-cancer promoters of triterpene components (anti -tumour promoter) activity (Chairul et al., Phytochemistry 30 (12), 4105-4109 (1991); Phytochemistry 35 (5), 1305-1308 (1994)) and the like have been reported, and the polysaccharide di-glucan (D-glucan) Anti-cancer activity (T. Mizuno et al., Bull. Fac. Agr. Shizuoka Univ. 31, 49-64 (1981); T. Usui et al., Carbohydrate Res. 115, 273-280 (1983)) and antiviral action of water-soluble substances (SK Eo et al., Arch. Pharm. Res. 24 (1), 74-78 (2001)) and effects on immune responses (YS Kim et al., Kor. J. Pharmacogn. 25 (4), 348-355 (1994) )) And so on. In addition, the antimicrobial effect of the water extract of Janna Bulbulocho mushrooms (YS Kim et al., Yakhak Hoeji 38 (6), 742-748 (1994)), and the antiviral effect of the interferon combination effect (JH Kim et al., Yakhak Hoeji 43 ( 4), 464-468 (1999), SS Jung et al., Yakhak Hoeji 43 (4), 464-468 (1999)). However, there have been no reports of the use of Janna Bulbulo mushrooms in connection with diabetes.

당뇨병은 대표적인 성인성 대사질환으로 세계인구의 5%가 걸려있으며, 그로 인한 인명적, 경제적 손실은 실로 막대하다. 당뇨병 환자의 대부분은 경구용 치료제를 복용하고 있으나, 현재까지 안전한 치료제가 개발되어 있지 않은 실정이다. 인슐린 저항성(insulin resistance)이 가장 중요한 기전적 원인으로 알려져 있지만, 정확한 기전은 아직 확실하지 않으며, 다만 유전적인 소인과 환경의 복합적인 원인이 작용하는 것으로 밝혀져 있다. 당뇨병은 전세계적으로 3번째로 심각한 질병으로 2010년까지 약 2억5천만명의 당뇨병환자가 예상되며, 국내의 경우에도 계속적인 증가가 예견되고 있다. 국내 사망원인 중 7번째로 높으며, 여러 가지 합병증으로 생명이 5∼10년 단축된다고 보고되어 있다. 전체 당뇨병 환자의 90% 이상을 차지하고 있는 인슐린비의존성 당뇨병은 수명연장, 서양화된 식생활 및 생활방식에 의하여 급속히 증가하고 있다. 간, 근육, 지방조직과 같은 인슐린 표적세포의 인슐린 저항성과 췌장 베타세포에서 분비되는 인슐린의 상대적 결핍이 발병의 두 축을 이루는 것으로 알려져 있다. 그러나, 당뇨병은 기전이 복잡한 대사성 질환으로 약을 평생 복용해야 하므로 독성이 없는 약물의 개발이 필수적이나 아직 어려운 것이 현실이다.Diabetes is a representative adult metabolic disease, affecting 5% of the world's population, resulting in huge human and economic losses. Most diabetics are taking oral treatments, but no safe treatments have been developed. Insulin resistance is known to be the most important mechanism, but the exact mechanism is not yet clear, but a combination of genetic predisposition and environment has been found to work. Diabetes is the third most serious disease in the world, and about 250 million people with diabetes are expected by 2010, and the increase is expected in Korea. It is the 7th highest cause of death in Korea, and it is reported that life is shortened by 5 to 10 years due to various complications. Insulin-independent diabetes, which accounts for more than 90% of all diabetics, is rapidly increasing due to extended life, westernized diet and lifestyle. Insulin resistance of insulin target cells such as liver, muscle and adipose tissue and relative deficiency of insulin secreted from pancreatic beta cells are known to be two axes of the onset. However, diabetes is a complex metabolic disease with complicated mechanisms, so the drug must be taken for a lifetime, but the development of non-toxic drugs is essential but still difficult.

당뇨병의 가장 흔한 합병증인 당뇨성 말초신경증은 10년 이상 진행된 당뇨병의 50% 정도에서 그 증세를 보이기 시작한다. 그 초기 증상은 손, 특히 발의 감각 이상으로 시작되어 심한 통증이 계속되다가, 감각 상실과 함께 말초자율신경의 손상으로 혈류장애가 나타난다. 더 진행되면 통증이 없는 궤양과 감염이 나타나고심한 경우 손상된 사지의 절단이 필요한 경우도 있으며 급성인 경우 패혈증을 유발하여 생명이 위독한 경우까지 갈 수 있는 심각한 합병증이다. 당뇨성 말초신경증의 발생기전은 많은 연구에도 불구하고 아직 확실치 않다. 치료방법을 보면, 궁극적으로 말초신경증을 비롯한 여러 당뇨합병증의 치료제는 없다. 적극적인 혈당조절과 고지혈증, 고콜레스테롤, 과체중, 흡연 및 음주 등 위험인자의 제거가 합병증의 발생을 어느 정도 예방하거나 지연시키는 것으로 알려져 있지만, 일단 발생한 합병증을 치료하는 약물은 현재로서는 존재하지 않는다. 한편, 합병증의 발생을 지연하거나 예방할 수 있는 약물의 개발이 국내외 여러 연구기관에서 진행 중이지만 아직 임상에 쓰이는 것은 없다.Diabetic peripheral neuropathy, the most common complication of diabetes, begins to manifest in about 50% of diabetes that has progressed over 10 years. The initial symptoms begin with paresthesia of the hands, especially the feet, and continue with severe pain, resulting in impaired sensation and impairment of the peripheral autonomic nerves resulting in blood flow disorders. Further progression may result in painless ulcers and infections, and in severe cases, amputation of the damaged limbs may be necessary. The mechanism of development of diabetic peripheral neuropathy is not yet clear despite many studies. In terms of treatment, ultimately, there is no cure for various diabetic complications including peripheral neuropathy. Active glycemic control and elimination of risk factors such as hyperlipidemia, high cholesterol, overweight, smoking and drinking have been known to prevent or delay the occurrence of complications to some extent, but there are no drugs to treat complications once they occur. On the other hand, the development of drugs that can delay or prevent the occurrence of complications are in progress at various research institutes at home and abroad, but there is no clinical use.

본 발명자들은 상기와 같은 점들을 감안하여 안출한 것으로 독성이 없는 천연물질인 잔나비불로초버섯으로부터 버섯추출물을 추출하고, 이 버섯추출물의 당뇨병 또는 당뇨합병증에 대한 예방 또는 치료 효과를 규명함으로써 본 발명을 달성하였다.The present inventors have achieved the present invention by extracting the mushroom extract from the zanbibulocho mushroom, which is a non-toxic natural substance devised in view of the above points, and identifying the preventive or therapeutic effect of the mushroom extract on diabetes or diabetic complications. It was.

따라서, 본 발명의 목적은 독성이 없는 당뇨질환 예방 또는 치료용 잔나비불로초버섯 추출물을 제공함에 있다.Accordingly, it is an object of the present invention to provide an extract of Janna Bulbulocho mushroom for the prevention or treatment of non-toxic diabetes diseases.

본 발명의 상기 목적은 잔나비불로초버섯을 저급 알콜, 물, 아세톤 중 어느 하나의 유기용매로 추출하고, 상기 추출액을 감압농축 또는 냉동건조하여 잔나비불로초버섯 추출물을 제조하고, 상기 추출물의 당뇨병 또는 당뇨합병증에 대한 치료효과를 규명함으로써 달성하였다.The object of the present invention is to extract the Xavier bulgaro mushrooms with any one of the lower alcohol, water, acetone organic solvent, and the extract is concentrated under reduced pressure or lyophilized to prepare a Zannabibulo vinegar mushroom extract, diabetic or diabetic complications of the extract Achieved by identifying the therapeutic effect on

이하, 본 발명의 구성을 상세히 설명한다.Hereinafter, the configuration of the present invention will be described in detail.

도 1은 본 발명 잔나비불로초버섯 추출물이 당뇨합병증 모델동물의 좌골운동신경 전도속도 저하를 억제하는 효과를 나타낸 그래프이다.1 is a graph showing the effect of inhibiting the sciatic nerve nerve conduction rate decrease of the present invention Jangabibulocho mushroom extract in diabetic complication model animal.

본 발명에서는 잔나비불로초버섯을 저급 알코올 또는 물로 추출하거나 상기 과정에 더하여 증류수에 현탁하고 유기 용매로 추출하여 얻은 당뇨질환의 예방 또는 치료에 효능이 있는 잔나비불로초버섯 추출물을 제공한다. 상기 유기 용매로는 클로로포름, 에틸아세테이트, 아세톤 또는 알코올을 사용할 수 있다.In the present invention, it is extracted with low alcohol or water or low-alcohol or mushrooms in addition to the above process is suspended in distilled water and extracted with an organic solvent to provide an Xavier bulbulo mushroom extract that is effective in the prevention or treatment of diabetes diseases. As the organic solvent, chloroform, ethyl acetate, acetone or alcohol may be used.

본 발명 버섯추출물은 당뇨를 비롯한 당뇨합병증의 예방제, 치료제 및 치료보조제로 유용하게 사용될 수 있는데, 구체적으로 비만성 당뇨병, 인슐린의존성 당뇨병, 인슐린비의존성 당뇨병, 당뇨합병증 등을 포함하는 다양한 난치성, 만성질환이 포함된다.The mushroom extract of the present invention can be usefully used as a prophylactic, therapeutic and therapeutic aid for diabetic complications including diabetes, specifically, various intractable and chronic diseases including obesity diabetes mellitus, insulin dependent diabetes mellitus, insulin independent diabetes mellitus, diabetic complications and the like. This includes.

본 발명의 항당뇨질환용 약학적 조성물은 약학적으로 허용 가능한 담체 또는 부형제를 이용하여 제제화함으로써 단위 용량 형태로 제조되거나 또는 다용량 용기 내에 내입시켜 제조될 수 있다.The pharmaceutical composition for antidiabetic disease of the present invention may be prepared in unit dose form or formulated using a pharmaceutically acceptable carrier or excipient or incorporated into a multi-dose container.

이때, 제제 형태는 오일 또는 수성 매질 중의 용액, 현탁액 또는 유화액 형태, 엑스제, 분말제, 과립제, 정제 또는 캅셀제 형태일 수 있으며, 분산제, 현탁제 또는 안정화제를 더 함유할 수 있다.In this case, the form of the preparation may be in the form of a solution, suspension or emulsion in an oil or aqueous medium, in the form of extracts, powders, granules, tablets or capsules, and may further contain a dispersant, suspending or stabilizing agent.

본 발명에 따른 유효성분의 인체 투여량은 체내에서 활성성분의 흡수도, 불활성화율 및 배설속도, 환자의 연령, 성별 및 상태, 치료할 질병의 중증정도 등에따라 적절히 선택되나, 일반적으로 성인의 경우 10∼1500mg, 바람직하게는 50∼500mg이다. 따라서 본 발명의 단위투여형 제제는 전술한 유효량 범위를 고려하여 본 발명의 활성물질을 5∼500mg의 함량이 되도록 제조한다. 바람직하게는 10∼200 mg을 함유하도록 제형화하는 것이 좋다. 이렇게 제형화된 단위투여형 제제는 필요에 따라 약제의 투여를 감시하거나 관찰하는 전문가의 판단과 개인의 요구에 따라 전문화된 투약법을 사용하거나, 일정한 시간 간격으로 투여할 수 있으며, 바람직하게는 하루에 1회 내지 3회 투여할 수 있다.The human dose of the active ingredient according to the present invention is appropriately selected depending on the absorption rate, inactivation rate and excretion rate of the active ingredient in the body, the age, sex and condition of the patient, the severity of the disease to be treated, but in general 10 1500 mg, Preferably it is 50-500 mg. Therefore, the unit dosage form of the present invention is prepared in an amount of 5 to 500 mg of the active substance of the present invention in consideration of the above-mentioned effective amount range. Preferably it is formulated to contain 10-200 mg. The unit dosage form so formulated may be administered at regular intervals, using specialized dosing regimens, preferably per day, according to the discretion of the expert to monitor or observe the administration of the drug as needed and to the needs of the individual. It can be administered once to three times.

본 발명의 항당뇨질환용 추출물에 대하여 독성 실험을 실시하였다. 본 발명 버섯추출물을 마우스(군당 10마리)에 각각 경구투여한 후 30일 동안 관찰하여 사망률을 측정하였다. 이때, 본 발명의 약학적 조성물은 1,000mg/kg, 500mg/kg의 2단계로 투여하였고, 50% 치사량(LD50)은 1,000mg/kg 이상이었다. 이 결과는 기보고된 마우스의 복강투여에 의한 급성독성이 5,000mg/kg 이상이었다는 문헌(Y.S. Kim 등, Kor. J. Pharmacogn. 25(4), 348-355 (1994); Y.S. Kim 등, Yakhak Hoeji 38(6), 756-762 (1994))의 결과와 일치하였다.Toxicity test was performed on the extract for antidiabetic disease of the present invention. The mushroom extract of the present invention was orally administered to mice (10 mice per group) and observed for 30 days to determine mortality. At this time, the pharmaceutical composition of the present invention was administered in two stages of 1,000 mg / kg, 500 mg / kg, 50% lethal dose (LD 50 ) was more than 1,000 mg / kg. These results indicate that the reported acute toxicity of the mice intraperitoneally was 5,000 mg / kg or more (YS Kim et al., Kor. J. Pharmacogn. 25 (4), 348-355 (1994); YS Kim et al., Yakhak) Hoeji 38 (6), 756-762 (1994)).

이하, 본 발명의 구체적인 방법을 실시예를 들어 상세히 설명하고자 하지만 본 발명의 권리범위는 이들 실시예에만 한정되는 것은 아니다.Hereinafter, the specific method of the present invention will be described in detail with reference to Examples, but the scope of the present invention is not limited only to these Examples.

실시예 1 : 잔나비불로초버섯으로부터 추출물 제조Example 1 Preparation of Extract from Janna Butterfly

시료인 잔나비불로초버섯을 건조시킨 후 1㎜ 크기로 분쇄하였다. 상기 분쇄물 300g을 취하여 환류냉각 장치에서 가온하면서 70℃에서 5ℓ의 메탄올로 3회 반복 추출하였다. 상기 추출액을 감압농축하여 최종 산물인 잔나비불로초버섯 추출물 10g을 얻었다.After drying, the sample was a butterfly butterfly mushrooms and ground to 1mm size. 300 g of the pulverized product was taken and extracted three times with 5 L of methanol at 70 DEG C while warming in a reflux condenser. The extract was concentrated under reduced pressure to obtain 10 g of Xavier bulgarocho mushroom extract, which was the final product.

또 다른 방법으로 메탄올 대신 증류수를 사용할 경우에는 버섯 분쇄물 300g을 취하여 6ℓ의 증류수로 2시간씩 끓여서 3회 반복 추출하였다. 상기 추출액을 냉동건조하여 최종 산물인 잔나비불로초버섯 추출물 21g을 얻었다.In another method, when distilled water was used instead of methanol, 300 g of the mushroom grounds were taken, and boiled with 6 L of distilled water for 2 hours, and extracted three times. The extract was freeze-dried to obtain 21 g of Xavier bulgarocho mushroom extract, which is a final product.

실시예 2 :Example 2: 당뇨병 모델동물에 대한 잔나비불로초버섯 추출물의 효과Effect of Xavier Butterfly Mushroom Extract on Diabetic Model Animals

렙틴(leptin)을 만드는 ob 유전자의 변이로 인하여 자연발생적으로 비만과 당뇨병를 수반하는 동물로 비만, 당뇨병, 비만형 당뇨병의 연구 및 시험에 일반적으로 사용되는 동물인 ob mouse (Lep ob )를 본 실시예의 모델동물로 사용하였다. 구체적으로, 평균 혈당치가 230mg/dl 내외인 8∼10 주령된 ob mouse (Lep ob )를 선별하여 사용하였다.Due to mutations in the ob gene that makes leptin, the animal is naturally associated with obesity and diabetes, and an ob mouse ( Lep ob ), an animal commonly used for the study and test of obesity, diabetes, and obesity type diabetes, is a model of this embodiment. Used as an animal. Specifically, 8-10 week old ob mouse ( Lep ob ) with an average blood glucose level of about 230 mg / dl was selected and used.

상기 실시예 1에 따라 제조된 잔나비불로초버섯 추출물은 0.5%의 CMC(carboxymethyl cellurose)를 사용하여 막사발에 갈아서 혼탁액으로 사용하였으며, 0.5%의 CMC는 음성 대조군으로도 사용하였다. 양성 대조군으로는 현재 임상적으로 사용되고 있는 약물인 Rasiglitazone (10mg/kg/ml)을 사용하였다.The Xanabulbulocho mushroom extract prepared according to Example 1 was used as a turbid solution by grinding in a membrane bowl using 0.5% CMC (carboxymethyl cellurose), 0.5% CMC was also used as a negative control. As a positive control, Rasiglitazone (10mg / kg / ml), a drug currently used clinically, was used.

투약 하루 전에 모든 개체의 혈당을 Glucose Analyzer II(Beckman Instrument 사)를 사용하여 측정하였다. 상기 시료들은 매일 투여하였으며, 혈당은 투여 5일 후에 상기와 동일한 방법으로 측정하였다.One day before dosing, blood glucose of all subjects was measured using Glucose Analyzer II (Beckman Instrument). The samples were administered daily, and blood glucose was measured in the same manner as above 5 days after administration.

양성 대조약물인 Rosiglitazone은 체중을 증가시키는 부작용이 있는 것으로 보고되어 있으므로, 이에 대비한 결과를 보기 위하여 혈액 채취와 함께 동물의 체중을 투여후 5일에 각각 측정하여 체중의 변화 관찰하였다.Rosiglitazone, a positive control drug, has been reported to have side effects of weight gain. Therefore, the weight of the animals was measured at the 5th day after the administration of blood and the change of body weight was observed in order to compare the results.

그 결과를 하기 표 1에 나타내었다.The results are shown in Table 1 below.

잔나비불로초버섯 추출물의 항당뇨 효과Anti-diabetic Effect of Xinavibulocho Mushroom Extract 혈중 포도당Blood glucose 체중weight 혈당치(mg/dl)Blood glucose level (mg / dl) 감소율(%)% Reduction 체중변화(g)Weight change (g) 변화율(%)% Change 대조군(vehicle)Control 235±42.25235 ± 42.25 -- 1.37±0.711.37 ± 0.71 -- Rasiglitazone(10mg/kg/ml)Rasiglitazone (10 mg / kg / ml) 134±10.98134 ± 10.98 42.942.9 1.45±1.021.45 ± 1.02 +35.9+35.9 버섯추출물(0.7mg/kg/ml)Mushroom Extract (0.7mg / kg / ml) 172±12.45172 ± 12.45 26.826.8 0.92±0.580.92 ± 0.58 -32.8-32.8

실시예 3 :Example 3: 당뇨합병증 모델동물에 대한 잔나비불로초버섯 추출물의 효과Effect of Xavier Butterfly Mushroom Extract on Diabetic Complication Model Animals

흰쥐에 당뇨병을 유발한 후 일정 기간동안 주어진 조건에서 유지하면 여러 가지 당뇨합병증이 유발되는데, 당뇨성 말초신경증의 경우에도 이 모델을 가장 많이 사용한다. 상기 모델에 있어서 당뇨성 말초신경증의 증상 중 가장 먼저 나타나는 것은 좌골운동신경 전도속도(Sciatic Motor Nerve Conduction Velocity)의 저하이다. 본 실시예에서는 대표적인 당뇨합병증인 당뇨성 말초신경증의 정도를 가장 정확하게 진단할 수 있는 좌골운동신경 전도속도를 정량적으로 측정함으로써 당뇨합병증에 대한 본 발명 잔나비불로초버섯 추출물의 효능을 규명하였다.Diabetes induces a number of diabetic complications in rats after a period of induction and for a period of time. The first symptom of diabetic peripheral neuropathy in this model is a decrease in sciatic motor neuron conduction velocity. In this example, the efficacy of the present invention of the present invention, Zannabibulocho mushroom extract for diabetic complications was quantitatively measured by quantitatively measuring the sciatic motor conduction rate that can most accurately diagnose the degree of diabetic peripheral neuropathy, a typical diabetic complication.

8 주령된 수컷 S-D 백서에 65mg/kg의 스트렙토조토신을 복강투여하고, 1 주 후 요당을 확인하였다. 상기 요당을 확인 한 당뇨병 쥐를 본 발명 잔나비불로초버섯 추출물 투여군과 대조군으로 나누어, 케이지(cage) 당 2 마리씩 넣어 관리하였다. 잔나비불로초버섯 추출물은 1일 1회 경구투여하였다. 약물 투여와 당뇨 유지 기간은 8주로 하였으며, 마지막 날 좌골운동신경 전도속도를 측정하였다.Eight weeks-old male S-D rats were intraperitoneally administered with 65 mg / kg of streptozotocin, and urine glucose was checked one week later. Diabetic rats confirming the urine glucose were divided into the present invention butterfly butterfly mushroom extract administration group and the control group, two animals per cage (cage) were administered. Xanabibulocho mushroom extract was administered orally once a day. The duration of drug administration and diabetes was 8 weeks and the sciatic nerve conduction velocity was measured on the last day.

8 주 유지한 당뇨병 쥐에 Ppentothal(40mg/kg, i.p.)을 복강주사하여 마취시킨 후, 한쪽 하지 대퇴부를 절개하여 좌골신경을 노출시켰다. 좌골신경이 척추로부터 나오는 시작부위(proximal point)와 말단부위(distal point)에 각각 자극전극을 꽂고, 발바닥 근육(plantar muscle)에는 측정전극을 꽂았다. 시작부위 자극시 측정전극에서 기록되는 활동전압까지의 잠복기에서 말단부위 자극시 활동전압까지의 잠복기를 뺀 값을 시작부위에서 말단부위까지의 신경전도에 걸리는 시간으로 잡았다. 시작부위와 말단부위 사이의 거리를 상기에서 계산한 시간으로 나누면 좌골운동신경 전도속도가 되는데, 이를 m/sec로 표시하였다. 본 발명 잔나비불로초버섯 추출물이 당뇨합병증 모델동물의 좌골운동신경 전도속도 저하를 억제하는 효과를 도 1에 나타내었다.Diabetic rats maintained for 8 weeks were intraperitoneally injected with Ppentothal (40 mg / kg, i.p.), and then one inferior thigh was cut to expose the sciatic nerve. Stimulation electrodes were inserted at the proximal and distal points of the sciatic nerve from the spine, and measurement electrodes were inserted at the plantar muscle. Subtracting the incubation period from the starting voltage to the active voltage recorded by the measuring electrode at the starting stimulus, the time taken for the nerve conduction from the starting region to the distal end was subtracted. Dividing the distance between the start and the distal end by the time calculated above is the sciatic nerve conduction velocity, which is expressed in m / sec. Figure 1 shows the effect of inhibiting the sciatic nerve nerve conduction slowing rate of the present invention Jangnabulocho mushroom extract in diabetic complications model animals.

이상, 상기 실시예에서 설명한 바와 같이 본 발명의 잔나비불로초버섯 추출물은 비만성 당뇨병 모델동물에서 혈당저하 효과가 우수할 뿐만 아니라, 비만과 기존 약물(Rasiglitazone)의 부작용으로 나타나는 체중 증가를 강하게 억제할 수 있으며, 만성 당뇨질환의 대표적인 합병증인 당뇨성 말초신경증에서 좌골운동신경 전도속도의 저하를 현저하게 억제할 수 있으므로, 본 발명은 당뇨병 및 당뇨합병증환자의 질환 치료와 관련한 의약 산업상 매우 유용한 발명인 것입니다.As described above, as described in the above embodiment, the Janna Bulbulocho mushroom extract of the present invention not only has an excellent hypoglycemic effect in obese diabetic model animals, but also strongly inhibits weight gain caused by side effects of obesity and conventional drugs (Rasiglitazone). In addition, the present invention is a very useful invention in the pharmaceutical industry related to the treatment of diseases of diabetic and diabetic complications because it can significantly suppress the decrease in the sciatic nerve conduction rate in diabetic peripheral neuropathy, a typical complication of chronic diabetes diseases. .

Claims (1)

유기용매를 사용하여 잔나비불로초버섯(Ganoderma applanatum)으로부터 추출한 잔나비불로초버섯 추출물을 유효성분으로 함유함을 특징으로 하는 당뇨병 또는 당뇨합병증 치료용 약학적 조성물.Pharmaceutical composition for the treatment of diabetes mellitus or diabetic complications, characterized in that it comprises an extract of Jangnabulo Bulchocho mushrooms extracted from Ganoderma applanatum using an organic solvent as an active ingredient.
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KR101969433B1 (en) * 2018-10-12 2019-04-17 김병천 Composition comprising product of two stage cultivation using Ganoderma applanatum and Ceriporia lacerata K1 mycelium for preventing or treating diabetes mellitus
KR101981571B1 (en) * 2018-10-12 2019-05-24 김병천 Composition comprising product of two stage cultivation using Ganoderma applanatum and Ceriporia lacerata K1 mycelium for preventing or treating hepatic injury

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KR101969433B1 (en) * 2018-10-12 2019-04-17 김병천 Composition comprising product of two stage cultivation using Ganoderma applanatum and Ceriporia lacerata K1 mycelium for preventing or treating diabetes mellitus
KR101981571B1 (en) * 2018-10-12 2019-05-24 김병천 Composition comprising product of two stage cultivation using Ganoderma applanatum and Ceriporia lacerata K1 mycelium for preventing or treating hepatic injury

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