KR20220005153A - Pharmaceutical composition comprising the ethylacetate fraction of root ethanol extract of cannabis sativa l.as an effective component for prevention or treatment of diabetes and health functional food comprising the same - Google Patents
Pharmaceutical composition comprising the ethylacetate fraction of root ethanol extract of cannabis sativa l.as an effective component for prevention or treatment of diabetes and health functional food comprising the same Download PDFInfo
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- KR20220005153A KR20220005153A KR1020200082612A KR20200082612A KR20220005153A KR 20220005153 A KR20220005153 A KR 20220005153A KR 1020200082612 A KR1020200082612 A KR 1020200082612A KR 20200082612 A KR20200082612 A KR 20200082612A KR 20220005153 A KR20220005153 A KR 20220005153A
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- hemp
- extract
- root
- diabetes
- health functional
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Classifications
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- 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)
-
- 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
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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
-
- 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
Description
본 발명은 대마 뿌리(Root of Cannabis sativa L.) 추출물을 유효성분으로 함유하는 당뇨병(diabetes)의 예방 또는 치료용 약학적 조성물 및 건강 기능 식품에 관한 것으로서, 보다 구체적으로는, 대마 뿌리 에탄올 추출물의 헥센 분획물 또는 에틸아세테이트 분획물을 유효성분으로 함유하는 알파-글루코시다아제(α-glucosidase) 저해를 통한 당뇨병의 예방 또는 치료/개선용 약학적 조성물 및 건강 기능 식품에 관한 것이다.The present invention relates to a pharmaceutical composition for the prevention or treatment of diabetes mellitus and a health functional food containing an extract of cannabis sativa L. as an active ingredient, and more particularly, to a ethanol extract of hemp root It relates to a pharmaceutical composition and health functional food for preventing or treating/improving diabetes through α-glucosidase inhibition containing a hexene fraction or an ethyl acetate fraction as an active ingredient.
현대인에게 가장 흔한 질병중 하나인 당뇨병은 인슐린의 분비량이 부족하거나 정상적인 기능이 이루어지지 않는 등의 대사질환의 일종으로서 혈중 포도당 농도가 높은 것이 특징이며, 고혈당으로 인하여 여러 증상 및 징후를 일으킨다. 당뇨병은 제1형과 제2형으로 구분되는데, 제1형 당뇨병은 유전적 영향에 의해 인슐린을 전혀 생산하지 못하는 것이 원인이 되어 발생하며, 제2형 당뇨병은 인슐린 기능이 떨어져 인슐린 저항성(insulin resistance)이 원인으로 알려져 있다. 특히, 제2형 당뇨병은 식생활의 서구화에 따른 고열량, 고지방, 고단백의 식단, 운동부족, 스트레스 등 환경적인 요인이 크게 작용하는 것으로 알려져 있다. 당뇨병의 치료를 위해서는 제1형 당뇨병의 경우에는 인슐린 주사가 필수적이며, 제2형 당뇨병의 경우에는 생활습관 교정 및 약물치료가 필요하며, 대표적으로 인슐린 분비 촉진제(예, 레파글리나이드, 미티글이나이드) 및 소장에서의 탄수화물 흡수 지연제[글루코바이: 성분명-아카보즈(acarbose), 베이슨: 성분명-보글리보스(voglibose)] 등이 이용되고 있다. Diabetes mellitus, one of the most common diseases among modern people, is a type of metabolic disease such as insufficient insulin secretion or failure to function normally. Diabetes mellitus is divided into type 1 and type 2, type 1 diabetes is caused by the inability to produce insulin at all due to genetic influence, and type 2 diabetes is caused by poor insulin function and insulin resistance (insulin resistance) ) is known to be the cause. In particular, it is known that environmental factors such as high calorie, high fat, and high protein diet, lack of exercise, and stress play a major role in type 2 diabetes due to westernization of diet. For the treatment of diabetes, insulin injection is essential in the case of type 1 diabetes, and lifestyle modification and drug treatment are required in the case of type 2 diabetes. nide) and a carbohydrate absorption delaying agent in the small intestine [Glucoby: ingredient name-acarbose, Basin: ingredient name-voglibose], etc. are being used.
한편, 대마(Cannabis sativa L.)는 삼과의 한해살이풀로서 줄기 껍질을 삼베로 만들어 의복, 신발, 공예품으로 이용하고, 줄기 속대는 종이, 건축재, 씨앗은 식품 및 약용으로 사용하여 왔다. 또한, 대마씨 기름은 오일 및 화장품으로 이용하는 매우 귀중한 식물 자원이다. 대마의 씨앗 껍질, 꽃봉오리 및 잎에는 환각 성분인 THC(Tetrahydrocanabinol)를 포함하여 환각제로 오용되기도 하였다. On the other hand, cannabis ( Cannabis sativa L.) is an annual plant of the Hemp family, and the stem bark is made of hemp and used for clothes, shoes, and crafts, and the stem inner material has been used for paper, building materials, and seeds for food and medicine. In addition, hemp seed oil is a very valuable plant resource used as an oil and cosmetic. Hemp seed husks, buds and leaves contain THC (Tetrahydrocanabinol), a hallucinogen, and have been misused as hallucinogens.
대마의 원산지는 중앙아시아이며, 현재는 전 세계 다양한 지역에서 재배하고 있다. 한방에서는 대마의 뿌리를 대마근이라 하여 어혈을 풀고 난산을 치료하며 석림(결석)이 나오게 하는데 사용하였으며, 대마의 줄기껍질(마피)은 타박상, 소변 곤란, 창통을 치료하는데 사용하였으며, 대마잎(대마초)은 천식, 진통, 마취 및 이뇨제로 사용하여 왔다. 또한, 대마꽃(마화)은 마비증상, 가려움증 치료, 대마 꽃이삭(마분)은 난산, 변비, 통풍 및 불면 치료에 사용하여 왔다. 한편, 대마씨는 한방에서는 마자인으로 부르며, 난치성 변비, 소갈증, 각종 통증 질환, 월경불순, 피부 질환 및 이질 등에 사용하며, 최근에는 신경염증 억제 및 신경세포 보호 활성 등이 알려져 있다. The origin of hemp is Central Asia, and it is now cultivated in various regions around the world. In oriental medicine, the root of cannabis is called hemp root, and it is used to relieve eohyeol, treat dysentery, and to produce stone lime (stone). cannabis) has been used as an asthma, analgesic, anesthetic, and diuretic. In addition, hemp flower (hemp flower) has been used for the treatment of paralysis and itchiness, and hemp flower ear (chaff) has been used to treat difficult childbirth, constipation, gout, and insomnia. On the other hand, hemp seeds are called mazain in oriental medicine, and are used for intractable constipation, small thirst, various pain diseases, menstrual irregularities, skin diseases, and dysentery.
대마 씨앗(마자인) 껍질의 환각성분(THC)을 탈각한 헴프씨드는 최근 건강식품으로 이용되고 있으며 고소하면서도 부드러운 식감을 가지고 있어 여타의 견과류와 유사한 맛을 나타내면서 단백질, 필수 아미노산 및 미네랄 함량이 높아 영양적으로 우수하며, 지방 함량이 25~35%로 높아 압착, 추출하여 식용유로도 이용되고 있다. 또한, 헴프씨드의 오일은 알파-리놀렌산(Alpha-Linolenic Acid; ALA)과 감마-리놀렌산(Gamma-Linolenic Acid; GLA) 등의 다가 불포화 지방산(Polyunsaturated fatty acid) 등이 풍부하여, 콜레스테롤 감소, 혈관염증 완화, 피부 질환, 아토피 감소 효과가 우수하다고 알려져 있다. Hemp seeds, which are peeled of the hallucinogenic component (THC) of the hemp seed (mazain) husk, are recently used as a health food. It is nutritionally excellent and has a high fat content of 25 to 35%, so it is used as cooking oil by pressing and extracting. In addition, hemp seed oil is rich in polyunsaturated fatty acids such as Alpha-Linolenic Acid (ALA) and Gamma-Linolenic Acid (GLA), thereby reducing cholesterol and vascular inflammation. It is known to be excellent in alleviating, reducing skin diseases and atopy.
대마와 관련된 연구는 대부분이 헴프씨드와 잎에 집중되어 있다. 헴프씨드와 관련된 연구로는 지방산 분석(Koh DH, 1990, Korean J Food Nutr 3: 201-206), 헴프씨드의 항산화 활성 펩타이드(Lu RR, 등, 2010. Food Chem 123: 1210-1218), 항고혈압성 펩타이드(Girgih AT 등, 2014. J. Funct Foods 6: 384-394), 신경세포 항염증 및 보호(Zhou Y 등, 2018. Phytochem Lett 23: 57-61) 등의 활성이 알려져 있다. 또한, 헴프씨드 섭취에 의한 인지기능의 개선(배길준 외, 2015, Journal of Korean Medicine Rehabilitation 25: 1-15) 및 아토피 피부염 완화(박신희, 2018, 조선대학교 박사논문)도 알려져 있다. 또한, 혈전증과 관련하여 헴프씨드를 식이로 공급한 경우 렛트에서의 혈소판 응집저해 활성이 보고(Richard MN 등, 2007, Journal of thrombosis and haemostasis, 5: 424-425)된 바 있으나, 이는 헴프씨드의 linoleic acid(LA) 및 alpha-linolenic acid(ALA) 등의 다가불포화지방산에 의한 것으로 알려져 있다. 헴프씨드와 관련된 특허로는 대한민국 등록특허 제10-1844849호 [헴프씨드 오일과 케나프씨드 오일을 함유하는 복합 조성물 및 그 제조 방법], 제10-1828217호 [대마씨 및 광천수를 배지로 한 동충하초 배양 및 생육방법], 제10-1492976호 [대마씨 성분이 함유된 면 및 그 제조방법], 제10-1886421호 [대마씨를 이용한 두부제조방법], 제10-2030923호 [햄프씨드를 이용한 두부형태의 가공식품 및 그 제조방법], 제10-1921331호 [대마씨를 함유한 육개장 칼국수와 그 제조방법], 제10-1820836호 [대마씨앗을 이용한 과립의 제조방법], 제10-1811000호 [청삼 종실유 및 그의 제조방법], 제10-0829997호 [청삼 종실유의 제조방법 및 그에 의해 제조된 청삼 종실유], 제10-0829999호 [청삼 종실유의 4급 아민염 제조방법 및 그에 의해 제조된 청삼 종실유의 4급 아민염], 제10-1871343호 [탈모 방지 비누의 제조방법], 제10-2011349호 [항고혈압 활성이 개선된 혼합 씨앗즙] 및 일본특허 JP-0044143 [PRODUCTION OF MISO CONTAINING THRESHED HEMPSEED]가 개시되어 있다. 또한, 대한민국 공개특허 제10-2012-0111125호 [마자인 추출물을 포함하는 신장암 치료용 조성물 및 건강 기능성 식품], 제10-2012-0111126호 [마자인 추출물을 포함하는 췌장암 치료용 조성물 및 건강 기능성 식품], 제10-2010-0008541호 [괄루인 또는 마자인 추출물을 함유하는 인간 중간엽 줄기세포의 지방세포로의 분화 촉진용 조성물]이 공개되어 있으며, 제10-2019-0066702호 [대마씨 음료 및 그 제조방법], 제10-2019-0068982호 [대마씨에서 단백질 및/또는 지방을 추출하는 방법], 제10-2019-0087701호 [시린이 방지용 대마씨유와 참마를 함유하는 치약조성물], 제10-2019-0066701호 [대마씨 탈각을 위한 전처리 방법], 제10-2017-0128028호 [대마씨를 함유하는 기능성 국수와 기능성 국수의 제조방법], 제10-2014-0081966호 [초임계유체를 이용한 청삼 종실유의 추출방법 및 그에 의해 제조된 청삼 종실유], 제10-2014-0081967호 [청삼 종실유를 함유한 아토피 피부 개선 기능성 화장품 조성물], 제10-2016-0014963호 [헴프팩 및 이의 제조방법], 제10-2013-0076658호 [한약밥 처방명과 당뇨밥]이 공개되어 있으며, 국제특허 WO-9531176 [COSMETIC PRODUCT CONTAINING HEMPSEED OIL AND METHOD FOR MANUFACTURING THE SAME], WO-0180358 [AGENT FOR PROMOTING HAIR GROWTH AND METHOD FOR PREPARING SAME]이 공개되어 있다. Most of hemp-related research has focused on hemp seeds and leaves. Studies related to hemp seeds include fatty acid analysis (Koh DH, 1990, Korean J Food Nutr 3: 201-206), hemp seed antioxidant activity peptide (Lu RR, et al., 2010. Food Chem 123: 1210-1218), anti- Activities such as hypertensive peptide (Girgih AT et al., 2014. J. Funct Foods 6: 384-394) and neuronal anti-inflammatory and protective (Zhou Y et al., 2018. Phytochem Lett 23: 57-61) are known. In addition, improvement of cognitive function by ingestion of hemp seeds (Kiljun Bae et al., 2015, Journal of Korean Medicine Rehabilitation 25: 1-15) and relief of atopic dermatitis (Shinhee Park, 2018, Chosun University doctoral thesis) are also known. In addition, in relation to thrombosis, platelet aggregation inhibitory activity was reported in rats when hemp seeds were fed in the diet (Richard MN et al., 2007, Journal of thrombosis and haemostasis, 5: 424-425), but this It is known to be caused by polyunsaturated fatty acids such as linoleic acid (LA) and alpha-linolenic acid (ALA). Patents related to hemp seeds include Korean Patent Registration Nos. 10-1844849 [Composite composition containing hemp seed oil and kenaf seed oil and manufacturing method thereof], No. 10-1828217 [Cordyceps with hemp seeds and mineral water as a medium. Cultivation and growth method], No. 10-1492976 [Noodles containing hemp seeds and manufacturing method thereof], No. 10-1886421 [Method for manufacturing tofu using hemp seeds], No. 10-2030923 [Tofu using hemp seeds Processed food in the form of processed food and its manufacturing method], No. 10-1921331 [Yukgaejang Kalguksu containing hemp seeds and its manufacturing method], No. 10-1820836 [Manufacturing method of granules using hemp seeds], No. 10-1811000 [ Cheongsam seed oil and production method thereof], Nos. 10-0829997 [Method for producing Cheongsam seed oil and cheongsam seed oil prepared thereby], Nos. 10-0829999 [Method for producing quaternary amine salt of Cheongsam seed oil and prepared by the same] Quaternary amine salt of cheongsam seed oil], No. 10-1871343 [Production method of anti-hair loss soap], No. 10-2011349 [Mixed seed juice with improved antihypertensive activity] and Japanese Patent JP-0044143 [PRODUCTION OF MISO CONTAINING] THRESHED HEMPSEED]. In addition, Korean Patent Laid-Open Nos. 10-2012-0111125 [Composition and Health Functional Food for Treatment of Kidney Cancer Containing Sojain Extract], No. 10-2012-0111126 [Composition and Health for Pancreatic Cancer Treatment Containing Sojain Extract] Functional food], No. 10-2010-0008541 [Composition for promoting the differentiation of human mesenchymal stem cells into adipocytes containing an extract of gualruin or yamjain] is disclosed, and No. 10-2019-0066702 [Hemp seed Beverage and its manufacturing method], No. 10-2019-0068982 [Method for extracting protein and/or fat from hemp seeds], No. 10-2019-0087701 [Toothpaste composition containing hemp seed oil and yam for preventing sore throat ], No. 10-2019-0066701 [Pre-treatment method for hemp seed shelling], No. 10-2017-0128028 [Method for producing functional noodles and functional noodles containing hemp seeds], No. 10-2014-0081966 [Second] Extraction method of cheongsam seed oil using critical fluid and cheongsam seed oil prepared thereby], No. 10-2014-0081967 [Functional cosmetic composition for improving atopic skin containing cheongsam seed oil], No. 10-2016-0014963 [Hemp Pack and its manufacturing method], No. 10-2013-0076658 [Oriental medicinal rice prescription name and diabetic rice] are published, and international patents WO-9531176 [COSMETIC PRODUCT CONTAINING HEMPSEED OIL AND METHOD FOR MANUFACTURING THE SAME], WO-0180358 [ AGENT FOR PROMOTING HAIR GROWTH AND METHOD FOR PREPARING SAME] has been released.
대마 잎에 대한 국내 연구는 매우 제한적이며, 환각제로 오용될 수 있어 법적으로 사용이 규제되고 있다. 반면, 외국의 경우 대마잎을 이용한 다양한 의약용 제품들이 개발되고 있으며, 다양한 칸나비노이드(cannabinoids) 성분 분리(Bakro F. et al., 2020. J Sep Sci. doi: 10.1002/jssc.201900822; Nagy DU et al., 2019. Chem Biodivers. 16: e1800562), 불면증 개선 및 뇌전증 치료 연구가 진행되어 있다(Choi S. et al., 2020. J Clin Neurophysiol. 37: 39-49). 기타 알려진 생리활성으로는 살충효과(Ahmed M. et al, 2020, Sci Rep. 10: 522.), 주변부 신경 손상(Peripheral nerve injury) 회복 효과(Aziz N. et al., 2019. Pak J Pharm Sci. 32 (Supplementary): 785-792), 혈중 콜레스테롤 저하 효과(Guo T. et al., 2018. Food Funct. 9: 6608-6617), 항생제 내성 세균 MRSA에 대한 항균 활성(Chakraborty S. et al., 2018. J Integr Med. 16: 350-357), 조직괴사 유도 활성(Shoyama Y et al., 2008, Plant Signal Behav. 3: 1111-1112), 암세포 증식억제 활성(Suzuki M. et al., 2017. Nat Prod Commun. 12: 759-761) 등이 보고되고 있다. Domestic studies on hemp leaves are very limited, and their use is regulated by law because they can be misused as hallucinogens. On the other hand, in foreign countries, various medicinal products using hemp leaves are being developed, and various cannabinoids are separated (Bakro F. et al., 2020. J Sep Sci. doi: 10.1002/jssc.201900822; Nagy DU et al., 2019. Chem Biodivers. 16: e1800562), insomnia improvement and epilepsy treatment studies are ongoing (Choi S. et al., 2020. J Clin Neurophysiol. 37: 39-49). Other known physiological activities include insecticidal effect (Ahmed M. et al, 2020, Sci Rep. 10: 522.), peripheral nerve injury recovery effect (Aziz N. et al., 2019. Pak J Pharm Sci) 32 (Supplementary): 785-792), blood cholesterol lowering effect (Guo T. et al., 2018. Food Funct. 9: 6608-6617), antimicrobial activity against antibiotic-resistant bacterium MRSA (Chakraborty S. et al. , 2018. J Integr Med. 16: 350-357), tissue necrosis inducing activity (Shoyama Y et al., 2008, Plant Signal Behav. 3: 1111-1112), cancer cell proliferation inhibitory activity (Suzuki M. et al., 2017. Nat Prod Commun. 12: 759-761) and the like have been reported.
대마 잎과 관련된 특허로는 대한민국 등록특허 제10-1714345호에 [정유 혼합물을 포함하는 미용학적 또는 피부학적 조성물 및 특히 민감성 또는 민감화 피부 관리에 사용되는 이의 용도]가 개시되어 있으며, 공개특허 제10-2018-0002839호에 [대마초 오일의 수소화], 제10-2017-0080608호에 [대마초 추출물 및 이의 제조 및 사용 방법], 제10-2019-0025485호에 [칸나비스 사티바 (CANNABIS SATIVA)로부터 칸나비크로메닉산 신타아제], 제10-2016-0141755호에 [단백질-결합된 칸나비노이드 조성물], 제10-2014-0037124호에 [신경병증성 통증의 치료에 사용하기 위한 칸나비노이드]가 알려져 있으며, 미국특허 US-20200060111에 [METHOD OF PRODUCTION OF PHYTOCANNABINOIDS FOR USE IN MEDICAL TREATMENTS], US-20190167749에 [THE OLEO GEL COMPOSITION AND DELIVERY SYSTEM WITH ACTIVE COMPOUNDS FROM CANNABIS SATIVA AND MENTHA ARVENSIS FOR REDUCTION OF INFLAMMATION AND PAIN IN DEEP TISSUES]가 공개되어 있다.As a patent related to cannabis leaf, Korean Patent Registration No. 10-1714345 [a cosmetic or dermatological composition containing an essential oil mixture and its use especially for sensitive or sensitive skin care] is disclosed, and Patent Publication No. 10 - From 2018-0002839 [Hydrogenation of cannabis oil], in No. 10-2017-0080608 [Cannabis extract and methods for its preparation and use], in No. 10-2019-0025485 [from CANNABIS SATIVA) Cannabichromenic acid synthase], in No. 10-2016-0141755 [protein-bound cannabinoid composition], in No. 10-2014-0037124 [Cannabinoids for use in the treatment of neuropathic pain ] is known, in US Patent US-20200060111 [METHOD OF PRODUCTION OF PHYTOCANNABINOIDS FOR USE IN MEDICAL TREATMENTS], US-20190167749 [THE OLEO GEL COMPOSITION AND DELIVERY SYSTEM WITH ACTIVE COMPOUNDS FROM CANNABIS SATIVA AND MENTHA ARVENSIS FOR PAIN IN DEEP TISSUES] has been released.
대마 줄기와 관련된 연구는 Muslo 등의 대마 hemp fiber 최적 생산을 위한 생육조건 및 대마종에 대한 연구(Muslo 등, 2019, Frontires in Plant Sci. doi: 10.3389/fpls.2018.01702)가 유일하다. The only study related to cannabis stems is Muslo et al.’s study on growth conditions and cannabis species for optimal production of hemp hemp fiber (Muslo et al., 2019, Frontires in Plant Sci. doi: 10.3389/fpls.2018.01702).
또한, 한방에서 어혈을 풀고 난산을 치료하며 석림(결석)이 나오게 하는데 사용하고 있는 대마 뿌리(대마근)에 대한 연구로는 뿌리 추출물에서 10종의 cannabinoids 화합물[trans-Δ9-tetrahydrocannabinol, cannabidiol, cannabigerol, cannabichromene, tetrahydrocannabivarian, cannabinol, (-)-trans-Δ8-tetrahydrocannabinol, cannabidiolic acid, cannabigerolic acid, and Δ9-tetrahydrocannabinolic acid-A]이 최근 확인되었으며(Gul. W 등, 2018, Plant Med. 84: 267-271), 뿌리의 대량 생산을 위한 부정근 배양(Wrobel T 등, 2018. Biotechnol. Lett. 40: 445-454), 뿌리에서 cannabisativine 알카로이드 분리(Turner CE 등, 1976. . Pharm. Sci. 65: 1084-1085)가 보고되어 있으며, 민간에서 통풍, 통증, 염증, 피부 화상, 구토, 감염, 성병 치료에 사용되어 왔다(Ryz N.R. 등 , 2017. Cannabis & Cannabinoid Res. 2.1: DOI: 10.1089/can.2017.0028). In addition, in the study of hemp root (cannabis root), which is used in oriental medicine to relieve eohyeol, treat dystonia, and produce stone stones, 10 kinds of cannabinoids compounds [trans-Δ9-tetrahydrocannabinol, cannabidiol, cannabigerol] , cannabichromene, tetrahydrocannabivarian, cannabinol, (-)-trans-Δ8-tetrahydrocannabinol, cannabidiolic acid, cannabigerolic acid, and Δ9-tetrahydrocannabinolic acid-A] were recently identified (Gul. W et al., 2018, Plant Med. 84: 267- 271), atypical root culture for mass production of roots (Wrobel T et al., 2018. Biotechnol. Lett. 40: 445-454), isolation of cannabisativine alkaloids from roots (Turner CE et al., 1976. . Pharm. Sci. 65: 1084- 1085) has been reported, and has been used in folklore to treat gout, pain, inflammation, skin burns, vomiting, infection, and sexually transmitted diseases (Ryz NR et al., 2017. Cannabis & Cannabinoid Res. 2.1: DOI: 10.1089/can.2017.0028). .
대마 뿌리와 관련된 특허로는 대한민국 공개특허 제10-2020-0064942호에 대마뿌리 추출물 및 대마씨 외종피 추출물을 혼합한 대마추출물을 유효성분으로 함유하는 [노화방지용 화장료 조성물]이 공개되어 있을 뿐, 현재까지 대마 뿌리의 강력한 항당뇨 활성에 대한 연구논문이나 특허는 없는 실정이다. As a patent related to hemp root, Korean Patent Publication No. 10-2020-0064942 discloses [Anti-aging cosmetic composition] containing as an active ingredient a hemp extract mixed with a hemp root extract and a hemp seed exoskeleton extract. So far, there are no research papers or patents on the potent antidiabetic activity of hemp root.
본 발명은 상기와 같은 종래 기술의 문제점을 해결하기 위하여 안출된 것으로서, 본 발명에서 해결하고자 하는 과제는 대마 뿌리 추출물을 유효성분으로 함유하는 당뇨병의 예방 또는 치료/개선용 약학적 조성물 및 건강 기능 식품을 제공하고자 하는 것이다.The present invention has been devised to solve the problems of the prior art as described above, and the problem to be solved in the present invention is a pharmaceutical composition for preventing or treating/improving diabetes and a health functional food containing hemp root extract as an active ingredient is intended to provide.
상기와 같은 과제를 해결하기 위하여, 본 발명은 대마(Cannabis sativa L.) 뿌리 추출물을 유효성분으로 함유하는 당뇨병의 예방 또는 치료용 약학적 조성물을 제공한다.In order to solve the above problems, the present invention provides a pharmaceutical composition for the prevention or treatment of diabetes containing an extract of Cannabis sativa L. root as an active ingredient.
상기 대마 뿌리 추출물은 대마 뿌리 에탄올 추출물의 헥센 분획물 또는 에틸아세테이트 분획물인 것이 바람직하다.The hemp root extract is preferably a hexene fraction or an ethyl acetate fraction of an ethanol extract of hemp root.
또한, 본 발명은 대마(Cannabis sativa L.) 뿌리 추출물을 유효성분으로 함유하는 당뇨병의 예방 또는 개선용 건강 기능 식품을 제공한다.In addition, the present invention provides a health functional food for preventing or improving diabetes containing the cannabis (Cannabis sativa L.) root extract as an active ingredient.
상기 대마 뿌리 추출물은 대마 뿌리 에탄올 추출물의 헥센 분획물 또는 에틸아세테이트 분획물인 것이 바람직하다.The hemp root extract is preferably a hexene fraction or an ethyl acetate fraction of an ethanol extract of hemp root.
본 발명의 당뇨병의 예방 또는 치료용 약학적 조성물 및 건강 기능 식품의 유효성분으로서의 대마(Cannabis sativa L.) 뿌리 추출물은, 본 명세서의 실시예를 통해 증명된 바와 같이, 당뇨병의 예방 또는 치료/개선용 의약품 및 건강 기능 식품으로 사용할 수 있는 뛰어난 효과가 있다. 뿐만 아니라, 본 발명의 대마(Cannabis sativa L.) 뿌리 추출물 및 이의 활성 분획물은 열 안정성이 우수하고, pH 2의 산성조건 및 혈장 내에서도 전분분해효소 저해 활성의 손실이 나타나지 않아, 액상, 분말, 환, 정 등의 다양한 형태로 손쉽게 가공될 수 있어 제약 산업 및 식품 산업상 매우 유용하게 이용될 수 있다. The cannabis sativa L. root extract as an active ingredient of the pharmaceutical composition for preventing or treating diabetes and a health functional food of the present invention, as demonstrated through the examples of the present specification, prevents or treats/improves diabetes It has excellent effects that can be used as pharmaceuticals and health functional foods. In addition, the cannabis ( Cannabis sativa L.) root extract and active fraction thereof of the present invention have excellent thermal stability, and no loss of starchase inhibitory activity even under acidic conditions of pH 2 and plasma, liquid, powder, pill Since it can be easily processed into various shapes such as tablets, tablets, etc., it can be very usefully used in the pharmaceutical and food industries.
이하, 본 발명을 상세하게 설명한다. Hereinafter, the present invention will be described in detail.
본 발명의 발명자들은 대마의 항당뇨 효능을 검정하기 위하여, 일정 방법으로 대마 뿌리, 줄기 및 종자(헴프씨드) 추출물을 조제하고, 이의 β-amylase 및 α-glucosidase에 대한 저해활성을 평가한 결과, 대마(Cannabis sativa L.) 뿌리 추출물과 이의 헥센 분획물 및 에틸아세테이트 분획물에서 강력한 α-glucosidase 효소 저해활성을 확인하였다. 상기 활성 분획물은 인간 적혈구에 대해 용혈활성은 나타내지 않으면서도, 열 안정성과 산 안정성이 우수한 특징을 가짐을 확인함으로써 상기 추출물 및 분획물을 당뇨병의 예방 또는 치료/개선용 약학적 조성물 및 건강 기능 식품으로 활용하고자 하였다.The inventors of the present invention prepared hemp root, stem and seed (hemp seed) extracts by a certain method in order to test the antidiabetic efficacy of hemp, and evaluated their inhibitory activity on β-amylase and α-glucosidase, Strong α-glucosidase enzyme inhibitory activity was confirmed in Cannabis sativa L. root extract and its hexene fraction and ethyl acetate fraction. By confirming that the active fraction has excellent thermal stability and acid stability while not exhibiting hemolytic activity against human red blood cells, the extract and fraction are used as pharmaceutical compositions and health functional foods for preventing or treating/improving diabetes mellitus wanted to
따라서, 본 발명은 대마(Cannabis sativa L.) 뿌리 추출물을 유효성분으로 함유하는 당뇨병의 예방 또는 치료용 약학적 조성물을 제공한다.Accordingly, the present invention provides a pharmaceutical composition for preventing or treating diabetes mellitus containing a cannabis (Cannabis sativa L.) root extract as an active ingredient.
상기 대마 뿌리 추출물은 대마 뿌리 에탄올 추출물의 헥센 분획물 또는 에틸아세테이트 분획물인 것이 바람직하다.The hemp root extract is preferably a hexene fraction or an ethyl acetate fraction of an ethanol extract of hemp root.
또한, 본 발명은 대마(Cannabis sativa L.) 뿌리 추출물을 유효성분으로 함유하는 당뇨병의 예방 또는 개선용 건강 기능 식품을 제공한다.In addition, the present invention provides a health functional food for preventing or improving diabetes containing the cannabis (Cannabis sativa L.) root extract as an active ingredient.
상기 대마 뿌리 추출물은 대마 뿌리 에탄올 추출물의 헥센 분획물 또는 에틸아세테이트 분획물인 것이 바람직하다.The hemp root extract is preferably a hexene fraction or an ethyl acetate fraction of an ethanol extract of hemp root.
이하에서는, 본 발명의 대마(Cannabis sativa L.) 뿌리 추출물의 제조 방법 및 효능 실험 등을 보다 구체적으로 설명한다.Hereinafter, a method for preparing a cannabis sativa L. root extract of the present invention and an efficacy test will be described in more detail.
본 발명은 대마의 다양한 부위로부터 용매 추출을 통해 추출물을 조제하는 단계; 상기 추출물의 항당뇨 활성 평가 단계; 대마 뿌리 추출물의 순차적 유기용매 분획물을 조제하는 단계; 상기 분획물들의 항당뇨 활성 평가 단계; 및 안정성 조사 단계를 포함한다.The present invention comprises the steps of preparing an extract through solvent extraction from various parts of cannabis; Antidiabetic activity evaluation step of the extract; preparing sequential organic solvent fractions of the hemp root extract; Evaluating the antidiabetic activity of the fractions; and a stability investigation step.
본 발명의 조성물에 포함되는 "대마 뿌리 추출물"은 대마의 뿌리를 유기용매로 추출하는 단계 및 상기 추출액을 0.06mm 이하의 여과망을 사용하여 여과하고, 이를 감압농축하는 단계에 의해 수득될 수 있다. "Hemp root extract" included in the composition of the present invention can be obtained by extracting the hemp root with an organic solvent, filtering the extract using a filtration network of 0.06 mm or less, and concentrating it under reduced pressure.
본 발명에서 사용되는 유기용매는 물(냉수, 열수), 헥센, 메틸렌클로라이드, 아세톤, 주정, 탄소수 1~4의 무수 또는 함수 저급 알코올(메탄올, 에탄올, 주정, 프로판올, 부탄올 등), 상기 저급알코올과 물과의 혼합용매 등을 이용할 수 있으며, 열수 또는 95% 에탄올 추출이 바람직하다.The organic solvent used in the present invention is water (cold water, hot water), hexene, methylene chloride, acetone, alcohol, anhydrous or hydrous lower alcohol having 1 to 4 carbon atoms (methanol, ethanol, alcohol, propanol, butanol, etc.), the lower alcohol A mixed solvent of and water, etc. can be used, and hot water or 95% ethanol extraction is preferable.
상기 에탄올 추출물은 헥센, 에틸아세테이트 및 부탄올의 유기용매로 순차 또는 각각 분획하여 헥센 분획물, 에틸아세테이트 분획물 및 부탄올 분획물 및 물 잔류물을 추가적으로 수득할 수 있다.The ethanol extract may be sequentially or individually fractionated with an organic solvent of hexene, ethyl acetate and butanol to additionally obtain a hexene fraction, an ethyl acetate fraction and a butanol fraction and a water residue.
본 발명의 대마 뿌리 추출물은 감압건조 및 동결건조, 또는 분무건조 등과 같은 통상적인 분말화 과정을 거쳐 분말로 제조될 수 있다. 이들은 혈장 내의 다양한 분해효소에 분해되지 않으며, 100℃의 열처리와 pH 2의 인체 위 내의 pH에서도 활성을 유지한다.The cannabis root extract of the present invention may be prepared as a powder through a conventional powdering process such as drying under reduced pressure, freeze drying, or spray drying. They are not degraded by various degrading enzymes in plasma, and they maintain activity even at 100°C heat treatment and at pH 2 in the human stomach.
본 발명의 대마 뿌리 추출물은 강력한 α-glucosidase에 대한 전분 분해효소 저해활성을 나타내어, 제1형 당뇨병, 제2형 당뇨병 또는 당뇨병성 망막증, 당뇨병성 신증 등과 같은 당뇨 합병증 등의 예방 및 치료/개선과 관련되는 약학적 조성물 및 건강 기능 식품의 소재로 사용될 수 있다.The cannabis root extract of the present invention exhibits a strong inhibitory activity of starch degrading enzyme against α-glucosidase, thereby preventing, treating/improving, It can be used as a material for related pharmaceutical compositions and health functional foods.
바람직한 구체예로서, 본 발명의 항당뇨 조성물은 약학적 조성물의 용도로서 적용될 수 있다.In a preferred embodiment, the antidiabetic composition of the present invention can be applied as a pharmaceutical composition use.
본 발명의 유효 성분을 포함하는 약학적 조성물은 각각의 사용 목적에 맞게 통상의 방법에 따라 산제, 과립제, 정제, 캡슐제, 현탁제, 에멀젼, 시럽, 에어로졸 등의 경구 제형, 멸균 주사용액의 주사제 등 다양한 형태로 제형화하여 사용할 수 있으며, 경구 투여하거나 정맥 내, 복강 내, 피하, 직장, 국소 투여 등을 포함한 다양한 경로를 통해 투여될 수 있다.The pharmaceutical composition comprising the active ingredient of the present invention can be prepared according to a conventional method according to the purpose of use. Oral formulations such as powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols, etc., and injections of sterile injection solutions It can be formulated and used in various forms, such as oral administration, or administered through various routes including intravenous, intraperitoneal, subcutaneous, rectal, topical administration, and the like.
이러한 약학적 조성물에는 추가적으로 담체, 부형제 또는 희석제 등이 더 포함될 수 있으며, 포함될 수 있는 적합한 담체, 부형제 또는 희석제의 예로는 락토오스, 덱스트로오스, 수크로오스, 솔비톨, 만니톨, 자일리톨, 에리쓰리톨, 말티톨, 전분, 아카시아 고무, 알지네이트, 젤라틴, 칼슘 포스페이트, 칼슘 실리케이트, 셀룰로스, 메틸 셀룰로스, 비정질 셀룰로스, 폴리비닐 피롤리돈, 물, 메틸하이드록시벤조에이트, 프로필하이드록시벤조에이트, 탈크, 마그네슘 스테아레이트 및 광물유 등을 들 수 있다. 또한, 본 발명의 약학적 조성물은 충전제, 항응집제, 윤활제, 습윤제, 향료, 유화제, 방부제 등을 추가로 더 포함할 수도 있다.The pharmaceutical composition may additionally include a carrier, excipient or diluent, and the like, and examples of suitable carriers, excipients or diluents that may be included include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, Starch, gum acacia, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, amorphous cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil and the like. In addition, the pharmaceutical composition of the present invention may further include a filler, an anti-agglomeration agent, a lubricant, a wetting agent, a flavoring agent, an emulsifier, a preservative, and the like.
바람직한 구체예로서, 경구 투여를 위한 고형 제제에는 정제, 환제, 산제, 과립제, 캡슐제 등이 포함되며, 이러한 고형 제제는 상기 약학적 조성물에 적어도 하나 이상의 부형제, 예를 들면, 전분, 탄산칼슘, 수크로오스, 락토오스, 젤라틴 등을 혼합하여 제형화한다. 또한, 단순한 부형제 이외에 마그네슘 스테아레이트, 탈크 등과 같은 윤활제가 사용될 수도 있다.In a preferred embodiment, solid preparations for oral administration include tablets, pills, powders, granules, capsules, and the like, and such solid preparations include at least one excipient in the pharmaceutical composition, for example, starch, calcium carbonate, It is formulated by mixing sucrose, lactose, gelatin, and the like. In addition to simple excipients, lubricants such as magnesium stearate, talc and the like may be used.
바람직한 구체예로서, 경구용 액상 제제로는 현탁제, 내용액제, 유제, 시럽제 등이 예시될 수 있으며, 흔히 사용되는 단순 희석제인 물, 액체 파라핀 이외에 여러 가지 부형제, 예를 들면, 습윤제, 감미제, 방향제, 보존제 등이 포함될 수 있다.As a preferred embodiment, the oral liquid formulation may include suspensions, solutions, emulsions, syrups, etc., and various excipients, for example, wetting agents, sweetening agents, in addition to water and liquid paraffin, which are commonly used simple diluents, Perfumes, preservatives, and the like may be included.
바람직한 구체예로서, 비경구 투여를 위한 제제에는 멸균된 수용액제, 비수성용제, 현탁제, 유제, 동결건조제, 좌제 등을 예시할 수 있다. 비수성용제, 현탁제에는 프로필렌글리콜, 폴리에틸렌글리콜, 올리브 오일과 같은 식물성 기름, 에틸올레이트와 같은 주사 가능한 에스테르 등이 포함될 수 있다. 주사제에는 용해제, 등장화제, 현탁화제, 유화제, 안정화제, 방부제 등과 같은 종래의 첨가제가 포함될 수 있다.As a preferred embodiment, sterile aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-drying agents, suppositories, etc. can be exemplified as formulations for parenteral administration. Non-aqueous solvents and suspensions may include propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate. Injections may contain conventional additives such as solubilizing agents, isotonic agents, suspending agents, emulsifying agents, stabilizing agents, and preservatives.
본 발명의 유효 성분은 약제학적으로 유효한 양으로 투여한다. 본 발명에서, "약제학적으로 유효한 양"은 의학적 치료에 적용 가능한 합리적인 수혜/위험 비율로 질환을 치료하기에 충분한 양을 의미하며, 유효 용량 수준은 환자의 질환의 종류, 중증도, 약물의 활성, 약물에 대한 민감도, 투여 시간, 투여 경로 및 배출 비율, 치료 기간, 동시 사용되는 약물을 포함한 요소 및 기타 의학 분야에 잘 알려진 요소에 따라 결정될 수 있다. 본 발명의 약학적 조성물은 개별 치료제로 투여하거나 다른 치료제와 병용하여 투여될 수 있고, 종래의 치료제와 순차적으로 또는 동시에 투여될 수 있으며, 단일 또는 다중 투여될 수 있다. 상기한 요소들을 모두 고려하여 부작용 없이 최소한의 양으로 최대 효과를 얻을 수 있는 양을 투여하는 것이 중요하며, 이는 당업자에 의해 용이하게 결정될 수 있다.The active ingredient of the present invention is administered in a pharmaceutically effective amount. In the present invention, "pharmaceutically effective amount" means an amount sufficient to treat a disease with a reasonable benefit/risk ratio applicable to medical treatment, and the effective dose level is determined by the type, severity, activity of the drug, and the type of disease in the patient; Sensitivity to the drug, time of administration, route of administration and excretion rate, duration of treatment, factors including concomitant drugs and other factors well known in the medical field. The pharmaceutical composition of the present invention may be administered as an individual therapeutic agent or may be administered in combination with other therapeutic agents, may be administered sequentially or simultaneously with conventional therapeutic agents, and may be administered singly or multiple times. In consideration of all of the above factors, it is important to administer an amount that can obtain the maximum effect with a minimum amount without side effects, which can be easily determined by those skilled in the art.
바람직한 구체예로서, 본 발명의 약학적 조성물에서 유효성분의 유효량은 환자의 나이, 성별, 체중에 따라 달라질 수 있으며, 일반적으로는 체중 ㎏ 당 1 내지 5,000mg, 바람직하게는 100 내지 3,000mg을 매일 또는 격일 투여하거나 1일 1 내지 3회로 나누어 투여할 수 있다. 그러나, 투여 경로, 질병의 중증도, 성별, 체중, 연령 등에 따라서 증감될 수 있으므로 상기 투여량이 어떠한 방법으로도 본 발명의 범위를 한정하는 것은 아니다.In a preferred embodiment, the effective amount of the active ingredient in the pharmaceutical composition of the present invention may vary depending on the age, sex, and weight of the patient, and generally 1 to 5,000 mg, preferably 100 to 3,000 mg per kg of body weight daily Alternatively, it may be administered every other day or divided into 1 to 3 times a day. However, since it may increase or decrease depending on the route of administration, disease severity, sex, weight, age, etc., the dosage is not intended to limit the scope of the present invention in any way.
본 발명의 약학적 조성물은 다양한 경로를 통하여 대상에 투여될 수 있다. 투여의 모든 방식은 예상될 수 있는데, 예를 들면, 경구, 직장 또는 정맥, 근육, 피하, 자궁내 경막 또는 뇌혈관 내(intracerebroventricular) 주사에 의해 투여될 수 있다.The pharmaceutical composition of the present invention may be administered to a subject through various routes. Any mode of administration can be envisaged, for example, by oral, rectal or intravenous, intramuscular, subcutaneous, intrauterine dural or intracerebroventricular injection.
본 발명에서 "투여"는 임의의 적절한 방법으로 환자에게 소정의 물질을 제공하는 것을 의미하며, 본 발명의 약학적 조성물의 투여 경로는 목적 조직에 도달할 수 있는 한 일반적인 모든 경로를 통하여 경구 또는 비경구 투여될 수 있다. 또한, 본 발명의 조성물은 유효성분을 표적 세포로 전달할 수 있는 임의의 장치를 이용해 투여될 수도 있다.In the present invention, "administration" means providing a predetermined substance to a patient by any suitable method, and the administration route of the pharmaceutical composition of the present invention is oral or parenteral through all general routes as long as it can reach the target tissue. It can be administered orally. In addition, the composition of the present invention may be administered using any device capable of delivering an active ingredient to a target cell.
본 발명에서 "대상"은, 특별히 한정되는 것은 아니지만, 예를 들어, 인간, 원숭이, 소, 말, 양, 돼지, 닭, 칠면조, 메추라기, 고양이, 개, 마우스, 쥐, 토끼 또는 기니아 피그를 포함하고, 바람직하게는 포유류, 보다 바람직하게는 인간을 의미한다.In the present invention, the "subject" is not particularly limited, but includes, for example, humans, monkeys, cattle, horses, sheep, pigs, chickens, turkeys, quails, cats, dogs, mice, rats, rabbits or guinea pigs. and preferably a mammal, more preferably a human.
바람직한 구체예로서, 본 발명의 항당뇨 조성물은 건강 기능 식품의 용도로서 적용될 수도 있다.In a preferred embodiment, the antidiabetic composition of the present invention may be applied as a health functional food.
본 발명의 건강 기능 식품은 당뇨병의 예방 또는 개선에 효과적인 식품 및 음료 등에 다양하게 이용될 수 있다. 본 발명의 유효성분을 포함하는 식품으로는, 예를 들어, 각종 식품류, 음료, 껌, 차, 비타민 복합제, 건강보조 식품류 등이 있고, 분말, 과립, 정제, 캡슐 또는 음료인 형태로 사용할 수 있다.The health functional food of the present invention can be used in various ways, such as food and beverage effective for preventing or improving diabetes. Foods containing the active ingredient of the present invention include, for example, various foods, beverages, gums, tea, vitamin complexes, health supplements, and the like, and may be used in powder, granule, tablet, capsule or beverage form. .
본 발명의 유효성분은 일반적으로 전체 식품 중량의 0.01 내지 15중량%로 가할 수 있으며, 건강음료 조성물은 100ml를 기준으로 0.02 내지 10g, 바람직하게는 0.3 내지 1g의 비율로 가할 수 있다.In general, the active ingredient of the present invention may be added in an amount of 0.01 to 15% by weight of the total food weight, and the health drink composition may be added in a ratio of 0.02 to 10g, preferably 0.3 to 1g, based on 100ml.
본 발명의 건강 기능 식품은 지시된 비율로 필수 성분으로서 상기 화합물을 함유하는 것 외에 식품학적으로 허용 가능한 식품보조 첨가제, 예컨대, 천연 탄수화물 및 다양한 향미제 등을 추가 성분으로서 함유할 수 있다. The health functional food of the present invention may contain, as an additional ingredient, in addition to containing the above compound as an essential ingredient in the indicated ratio, a food pharmaceutically acceptable food supplement additive, such as natural carbohydrate and various flavoring agents.
상기 천연 탄수화물의 예로는 포도당, 과당 등의 단당류, 말토오스, 수크로오스 등의 이당류 및 덱스트린, 시클로덱스트린 등의 다당류와 같은 통상적인 당 및 자일리톨, 소르비톨, 에리쓰리톨 등의 당알코올이 있다. Examples of the natural carbohydrate include monosaccharides such as glucose and fructose, disaccharides such as maltose and sucrose, and common sugars such as polysaccharides such as dextrin and cyclodextrin, and sugar alcohols such as xylitol, sorbitol, and erythritol.
상기 향미제로는 타우마틴, 레바우디오시드 A 또는 글리시르히진과 같은 스테비아 등의 천연 향미제 및 사카린, 아스파르탐 등의 합성 향미제를 사용할 수 있다. 상기 천연 탄수화물의 비율은 본 발명의 건강 기능 식품 100ml 당 일반적으로 약 1 내지 20g, 바람직하게는 약 5 내지 12g을 사용한다. 상기 외에 본 발명의 건강 기능 식품은 여러 가지 영양제, 비타민, 광물, 합성 풍미제 및 천연 풍미제 등의 풍미제, 착색제 및 중진제, 펙트산 및 그의 염, 알긴산 및 그의 염, 유기산, 보호성 콜로이드 증점제, pH 조절제, 안정화제, 방부제, 글리세린, 알코올, 탄산음료에 사용되는 탄산화제 등을 함유할 수 있다. 그 밖에 본 발명의 건강 기능 식품은 천연 과일 주스 및 과일 주스 음료 및 야채 음료 등의 제조를 위한 과육을 함유할 수도 있다. 이러한 성분은 독립적으로 또는 조합하여 사용할 수 있다. 이러한 첨가제의 비율은 본 발명의 유효성분 100중량부 당 0.01 내지 약 20중량부의 범위에서 선택되는 것이 일반적이다.As the flavoring agent, a natural flavoring agent such as stevia, such as taumatine, rebaudioside A, or glycyrrhizin, and a synthetic flavoring agent such as saccharin and aspartame may be used. The ratio of the natural carbohydrate is generally about 1 to 20 g, preferably about 5 to 12 g per 100 ml of the health functional food of the present invention. In addition to the above, the health functional food of the present invention includes various nutrients, vitamins, minerals, flavoring agents such as synthetic and natural flavoring agents, colorants and thickeners, pectic acid and its salts, alginic acid and its salts, organic acids, protective colloids It may contain thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohol, carbonation agents used in carbonated beverages, and the like. In addition, the health functional food of the present invention may contain natural fruit juice, fruit juice, and fruit for the production of fruit juice drinks and vegetable drinks. These components may be used independently or in combination. The ratio of these additives is generally selected in the range of 0.01 to about 20 parts by weight per 100 parts by weight of the active ingredient of the present invention.
이하에서는 실시예를 통하여 본 발명을 더욱 상세하게 설명한다. 하기 실시예는 본 발명의 바람직한 일 구체예일 뿐이며, 본 발명의 권리범위가 하기 실시예의 범위로 한정되는 것은 아니다.Hereinafter, the present invention will be described in more detail through examples. The following examples are only preferred embodiments of the present invention, and the scope of the present invention is not limited to the scope of the following examples.
[실시예][Example]
실시예 1: 대마의 다양한 부위로부터 에탄올 추출물 제조 및 이들의 유용성분 분석 Example 1: Preparation of ethanol extracts from various parts of cannabis and analysis of useful components thereof
2019년 경북 안동에서 재배된 대마 줄기 및 뿌리와, 2018년 수확한 국내 시판 대마 종자(헴프씨드)를 구입하여 에탄올 추출물을 조제하였다. 구체적으로는, 각각의 시료에 대해 10배의 95% 에탄올을 가하고, 상온에서 2회 반복 추출한 후 추출액을 모아 필터링한 후, 감압 농축하여 분말로 제조하여 에탄올 추출물을 제조하였다. 대마의 다양한 부위 추출물의 추출 수율과 이들의 유용성분 분석 결과는 표 1에 나타내었다. Hemp stems and roots grown in Andong, Gyeongsangbuk-do in 2019, and domestic hemp seeds harvested in 2018 were purchased and an ethanol extract was prepared. Specifically, 10 times 95% ethanol was added to each sample, extracted twice at room temperature, the extract was collected, filtered, and concentrated under reduced pressure to prepare a powder to prepare an ethanol extract. The extraction yields of extracts from various parts of cannabis and the results of analysis of their useful components are shown in Table 1.
[표 1] 대마의 다양한 부위 추출물의 추출효율 및 추출물들의 유용성분 분석[Table 1] Extraction efficiency of extracts from various parts of cannabis and analysis of useful components of extracts
먼저, 대마 종자와 줄기의 경우, 수율이 9.4~9.8%로 높게 나타났으나, 뿌리 추출물은 1.4% 수율을 보여 매우 낮은 수율을 보였다. 이는 줄기와 뿌리의 구성성분에서 큰 차이가 있음을 의미하고 있다. 추출물들의 유용성분 분석을 위해 총 폴리페놀, 총 플라보노이드, 총당 및 환원당 함량을 측정하였다. 이때, 총 폴리페놀 함량은 추출 검액 400μl에 50μl의 Folin-ciocalteau, 100μl의 Na2CO3 포화용액을 넣고, 실온에서 1시간 방치한 후 725nm에서 흡광도를 측정하였다. 표준시약으로는 tannic acid를 사용하였다. 총 플라보노이드 함량은 각각의 시료를 18시간 메탄올 교반 추출하고, 여과한 추출 검액 400μl에 90% diethylene glycol 4ml를 첨가하고, 다시 1N NaOH 40μl를 넣고 37℃에서 1시간 반응 후 420nm에서 흡광도를 측정하였다. 표준시약으로는 rutin을 사용하였다. 환원당은 DNS법으로, 총당은 phenol-sulfuric acid법을 이용하여 정량하였다. First, in the case of hemp seeds and stems, the yield was high as 9.4~9.8%, but the root extract showed a very low yield, showing a yield of 1.4%. This means that there is a big difference in the composition of the stem and the root. To analyze the useful components of the extracts, total polyphenols, total flavonoids, total sugars and reducing sugar contents were measured. At this time, for the total polyphenol content, 50 μl of Folin-ciocalteau and 100 μl of Na 2 CO 3 saturated solution were added to 400 μl of the extraction sample solution, and the absorbance was measured at 725 nm after standing at room temperature for 1 hour. As a standard reagent, tannic acid was used. For the total flavonoid content, each sample was extracted with methanol for 18 hours, 4 ml of 90% diethylene glycol was added to 400 μl of the filtered extraction sample, 40 μl of 1N NaOH was added, and the absorbance was measured at 420 nm after reaction at 37° C. for 1 hour. As a standard reagent, rutin was used. Reducing sugar was quantified by DNS method and total sugar was quantified by phenol-sulfuric acid method.
표 1에 나타낸 바와 같이, 폴리페놀 함량은 뿌리 추출물에서 가장 높은 14.3mg/g을 보인 반면, 종자 추출물은 0.8mg/g으로 매우 낮았다. 총 플라보노이드 함량은 줄기 추출물에서 가장 높은 3.8mg/g을 보인 반면, 뿌리 및 종자 추출물은 2.1~2.7mg/g으로 상대적으로 낮은 함량을 보였다. 총당 함량의 경우, 뿌리 추출물(153.5mg/g)과 줄기 추출물(120.0mg/g)에서 높은 함량을 보였으나, 종자 추출물은 12.0mg/g의 낮은 함량을 보였다. 환원당 함량에서도 줄기 추출물(49.9mg/g), 뿌리 추출물(41.1mg/g)이 종자 추출물(12.6mg/g)보다 높은 함량을 보였다. 따라서, 종자(헴프씨드)가 다량의 지질 및 단백질을 가진 반면, 대마 줄기 및 뿌리는 다량의 파이토케미컬(Phytochemical)을 가지고 있음을 확인하였다. As shown in Table 1, the polyphenol content was the highest in the root extract at 14.3 mg/g, while the seed extract was very low at 0.8 mg/g. The total flavonoid content was the highest in the stem extract at 3.8 mg/g, while the root and seed extract showed a relatively low content of 2.1 to 2.7 mg/g. As for the total sugar content, the root extract (153.5 mg/g) and the stem extract (120.0 mg/g) showed a high content, but the seed extract showed a low content of 12.0 mg/g. In terms of reducing sugar content, stem extract (49.9 mg/g) and root extract (41.1 mg/g) showed higher content than seed extract (12.6 mg/g). Therefore, it was confirmed that the seeds (hemp seeds) had a large amount of lipids and proteins, while the hemp stems and roots had a large amount of phytochemicals.
실시예 2: 다양한 부위의 대마 추출물의 항당뇨 활성 평가 Example 2: Evaluation of antidiabetic activity of cannabis extracts of various sites
실시예 1의 다양한 부위의 대마 추출물의 항당뇨 활성을 평가하였으며, in-vitro β-amylase 저해활성 및 α-glucosidase 저해활성을 평가하여 나타내었다.The antidiabetic activity of the hemp extract of various parts of Example 1 was evaluated, and the in-vitro β-amylase inhibitory activity and the α-glucosidase inhibitory activity were evaluated.
먼저, β-amylase(4-alpha-D-glucan maltohydrolase) 저해활성은 시료 2.5μl와 50mM phosphate buffer(pH 6.8)로 희석한 α-amylase(0.25U/ml) 25μl를 혼합하여 37℃에서 10분간 1차 반응한 후, 0.5% soluble starch(Samchun Chemicals Co., Korea) 25μl를 가하여 37℃에서 10분간 2차 반응한 후, 100℃에서 5분간 가열하여 반응을 정지시켰으며, 반응액에 150μl의 DNS(3,5-dinitrosalicylic acid, Sigma Co., st. Louis, USA) 용액을 가하여 100℃에서 5분간 가열하여 발색한 후, 상온에서 방냉하였다. 발색액은 540nm에서 흡광도를 측정하여 저해율을 계산하였다. First, β-amylase (4-alpha-D-glucan maltohydrolase) inhibitory activity was measured by mixing 2.5 μl of sample and 25 μl of α-amylase (0.25 U/ml) diluted with 50 mM phosphate buffer (pH 6.8) at 37°C for 10 minutes. After the first reaction, 25 μl of 0.5% soluble starch (Samchun Chemicals Co., Korea) was added and the second reaction was performed at 37° C. for 10 minutes, and then the reaction was stopped by heating at 100° C. for 5 minutes, and 150 μl of the reaction solution was added. A solution of DNS (3,5-dinitrosalicylic acid, Sigma Co., St. Louis, USA) was added, heated at 100° C. for 5 minutes to develop color, and then allowed to cool at room temperature. The inhibition rate was calculated by measuring the absorbance at 540 nm of the color developer.
저해율 (%) = [1-(시료 첨가구 효소활성/대조구 첨가구 효소활성)] x 100Inhibition rate (%) = [1-(enzyme activity in the sample addition group/enzyme activity in the control group)] x 100
α-glucosidase 저해활성은 pNPG(p-nitrophenol glucoside; Sigma Co., USA)를 이용하여 평가하였으며, 시료 2.5μl와 50mM Sodium acetate buffer(pH 5.6)로 희석한 α-glucosidase(0.25U/ml) 25μl를 혼합하여 37℃에서 10분간 1차 반응하고, 1mM pNPG 용액 25μl를 가하여 60℃에서 10분간 2차 반응하였다. 이후, 1M NaOH 25μl를 가하여 반응을 정지시키고, 405nm에서 흡광도를 측정하여 저해율을 계산하였다. α-glucosidase inhibitory activity was evaluated using pNPG (p-nitrophenol glucoside; Sigma Co., USA), 2.5 μl of sample and 25 μl of α-glucosidase (0.25 U/ml) diluted with 50 mM sodium acetate buffer (pH 5.6) was mixed and reacted first at 37°C for 10 minutes, and then 25 μl of 1 mM pNPG solution was added, followed by a second reaction at 60°C for 10 minutes. Then, 25 μl of 1M NaOH was added to stop the reaction, and the absorbance was measured at 405 nm to calculate the inhibition rate.
저해율 (%) = [1-(시료 첨가구 효소활성/대조구 첨가구 효소활성)] x 100Inhibition rate (%) = [1-(enzyme activity in the sample addition group/enzyme activity in the control group)] x 100
[표 2] 대마의 다양한 부위 추출물의 항당뇨 활성[Table 2] Antidiabetic activity of extracts from various parts of cannabis
표 2에 나타낸 바와 같이, 임상에서 당뇨병 치료제로 사용하고 있는 acarbose는 농도 의존적으로 강력한 β-amylase 저해활성 및 α-glucosidase 저해활성을 나타내었다. 본 발명의 대마 추출물의 경우, 줄기 추출물에서는 0.5mg/ml 농도에서 7.1%의 β-amylase 저해가 확인되었으나, α-glucosidase 저해활성은 2.9%로 상대적으로 미약하였다. 반면, 뿌리 및 헴프씨드 추출물의 경우, β-amylase 저해활성은 없었으나, α-glucosidase 저해활성은 각각 6.1% 및 14.5%의 우수한 저해 활성을 나타내었다.As shown in Table 2, acarbose, which is used as a treatment for diabetes in clinical practice, showed strong β-amylase inhibitory activity and α-glucosidase inhibitory activity in a concentration-dependent manner. In the case of the hemp extract of the present invention, 7.1% of β-amylase inhibition was confirmed in the stem extract at a concentration of 0.5 mg/ml, but the α-glucosidase inhibitory activity was relatively weak at 2.9%. On the other hand, in the case of root and hemp seed extracts, there was no β-amylase inhibitory activity, but α-glucosidase inhibitory activity showed excellent inhibitory activity of 6.1% and 14.5%, respectively.
실시예 3: 다양한 부위의 대마 추출물의 인간 적혈구 용혈 활성Example 3: Human erythrocyte hemolytic activity of cannabis extracts from various sites
대마의 줄기, 뿌리 및 헴프씨드 에탄올 추출물의 급성독성 가능성을 평가하기 위해 인간 적혈구 용혈 활성을 평가하였으며, 그 결과는 표 3에 나타내었다.In order to evaluate the acute toxicity potential of ethanol extracts of stems, roots and hemp seeds of cannabis, human erythrocyte hemolytic activity was evaluated, and the results are shown in Table 3.
이때, 용혈 활성은 기존의 보고(손호용, 2014년. Korean J. Microbiol. Biotechnol. 42: 285-292)에 준해 평가하였으며, 간단하게는 PBS로 3회 수세한 인간 적혈구 100μl를 96-well microplate에 가하고 다양한 농도의 시료용액 100μl를 가한 다음 37℃에서 30분간 반응시켰으며, 이후, 반응액을 10분간 원심분리(1,500rpm)하여 상등액 100μl를 새로운 microtiter plate로 옮긴 후 용혈에 따른 헤모글로빈 유출 정도를 414nm에서 측정하였다. 시료의 용매 대조구로는 DMSO(2%)를 사용하였으며, 적혈구 용혈을 위한 실험 대조구로는 Triton X-100(1mg/ml)를 사용하였다. 용혈 활성은 다음의 수식을 이용하여 계산하였다.At this time, hemolytic activity was evaluated according to an existing report (Ho-Yong Son, 2014. Korean J. Microbiol. Biotechnol. 42: 285-292), and 100 μl of human red blood cells washed three times with PBS was simply added to a 96-well microplate. 100 μl of sample solutions of various concentrations were added, followed by reaction at 37° C. for 30 minutes. After that, the reaction solution was centrifuged (1,500 rpm) for 10 minutes, and 100 μl of the supernatant was transferred to a new microtiter plate. was measured in DMSO (2%) was used as a solvent control of the sample, and Triton X-100 (1mg/ml) was used as an experimental control for hemolysis of red blood cells. Hemolytic activity was calculated using the following formula.
[표 3] 대마 부위별 추출물의 인간 적혈구 용혈 활성[Table 3] Human red blood cell hemolytic activity of extracts from each part of cannabis
먼저, 대조구로 사용된 DMSO와 물은 용혈 활성이 없었으며, triton X-100은 1mg/ml 농도에서 적혈구를 100% 용혈시킴을 확인하였다. 또한, 항암제, 항진균제로 사용되고 있는 amphotericin B의 경우 0.025mg/ml 농도에서 50% 이상 적혈구를 용혈시킴을 확인하였다. 한편, 대마 줄기 및 대마 뿌리 추출물은 1mg/ml 농도까지 전혀 적혈구 용혈현상이 나타나지 않아 급성독성 및 적혈구 용혈 활성은 없음을 확인하였으며, 대마씨(헴프씨드) 추출물의 경우 1mg/ml 농도에서 90% 이상의 용혈활성을 나타내었다. 특히, 대마씨 추출물은 0.25mg/ml 농도에서도 72%의 적혈구 용혈을 나타내어, 향후 헴프씨드 에탄올 추출물의 이용은 용도에 따라 사용량을 제한할 필요가 있음을 제시하고 있다. 본 발명에서는 용혈활성을 전혀 나타내지 않으면서도 우수한 α-glucosidase 저해활성을 나타내는 대마 뿌리 추출물을 당뇨병(특히 제2형 당뇨병)의 예방 및 치료/개선에 사용하고자 뿌리 추출물을 대량 제조하였다. 특히 대마 뿌리는 현재까지 특이한 용도가 없이 폐기되고 있는 실정이므로, 이를 이용한 경제적인 유용물질 생산재료로 이용가능하다. First, DMSO and water used as controls had no hemolytic activity, and it was confirmed that triton X-100 hemolyzed red blood cells 100% at a concentration of 1 mg/ml. In addition, in the case of amphotericin B, which is used as an anticancer agent and antifungal agent, it was confirmed that more than 50% of red blood cells were hemolyzed at a concentration of 0.025 mg/ml. On the other hand, hemp stem and hemp root extracts did not show any red blood cell hemolysis at a concentration of 1 mg/ml, confirming that there was no acute toxicity and hemolytic activity. It showed hemolytic activity. In particular, hemp seed extract showed 72% hemolysis of red blood cells even at a concentration of 0.25 mg/ml, suggesting that the use of hemp seed ethanol extract in the future needs to be limited depending on the intended use. In the present invention, a cannabis root extract exhibiting excellent α-glucosidase inhibitory activity without showing any hemolytic activity was prepared in large quantities to be used for the prevention, treatment/improvement of diabetes (especially type 2 diabetes). In particular, since the hemp root is being discarded without a specific use to date, it can be used as an economical material for producing useful substances using it.
실시예 4: 대마 뿌리 추출물의 순차적 유기용매 분획물의 제조 및 이들의 유용성분 분석 Example 4: Preparation of Sequential Organic Solvent Fractions of Hemp Root Extract and Analysis of Their Useful Components
실시예 1에서 조제된 대마 뿌리 에탄올 추출물을 대상으로 헥센, 에틸아세테이트, 부탄올로 순차적 유기용매 분획하였으며, 최종적으로 물 잔류물을 회수하였다. 이들의 분획효율과 성분 분석 결과는 표 4에 나타내었다. The ethanol extract of hemp root prepared in Example 1 was subjected to sequential organic solvent fractionation with hexene, ethyl acetate, and butanol, and finally the water residue was recovered. Their fractionation efficiency and component analysis results are shown in Table 4.
[표 4] 대마 뿌리 에탄올 추출물의 분획물의 수율 및 유용성분 분석[Table 4] Analysis of yield and useful components of fractions of hemp root ethanol extract
표 4에 나타낸 바와 같이, 대마 뿌리 에탄올 추출물 중 가장 많은 부분은 에틸아세테이트 분획(45.6%)로 이행되었으며, 부탄올 분획물, 헥센 분획물 및 물 잔류물 순으로 추출효율이 높게 나타났다. 따라서, 대마 뿌리 추출물은 상당량의 지용성 성분을 포함하고 있음을 확인하였다. 대마 뿌리 에탄올 추출효율과 분획효율을 고려하면, 에틸아세테이트 분획물은 대마 뿌리 100g당 0.64g을 회수할 수 있을 것으로 예측되었다. 한편, 총 폴리페놀 및 총 플라보노이드 함량 분석 결과, 에틸아세테이트 분획물에서 가장 높은 폴리페놀 함량(48.5mg/g) 및 플라보노이드 함량(19.5mg/g)을 나타내었다. 이는 물 잔류물에 비해 11배 높은 폴리페놀 함량 및 2.8배 높은 플라보노이드 함량이었다. 따라서, 대마 뿌리 추출물의 에틸아세테이트 분획물은 다양한 생리활성을 나타내리라 예상되었으며, 실제 분석결과, 상기 분획물은 강력한 항산화 활성 및 nitrite 소거능을 나타내었다. 따라서, 대마 뿌리 추출물의 에틸아세테이트 분획물은 우수한 항산화 활성, 발암억제 활성을 나타내어 항당뇨 활성에 부가적으로 기여하리라 예상된다.As shown in Table 4, the largest portion of the hemp root ethanol extract was transferred to the ethyl acetate fraction (45.6%), and the extraction efficiency was high in the order of the butanol fraction, the hexene fraction, and the water residue. Therefore, it was confirmed that the hemp root extract contained a significant amount of fat-soluble components. Considering the ethanol extraction efficiency and fractionation efficiency of hemp root, it was predicted that 0.64 g of ethyl acetate fraction could be recovered per 100 g of hemp root. On the other hand, as a result of analysis of total polyphenol and total flavonoid content, the ethyl acetate fraction showed the highest polyphenol content (48.5 mg/g) and flavonoid content (19.5 mg/g). This was an 11-fold higher polyphenol content and a 2.8-fold higher flavonoid content compared to the water residue. Therefore, the ethyl acetate fraction of the hemp root extract was expected to exhibit various physiological activities, and as a result of actual analysis, the fraction exhibited strong antioxidant activity and nitrite scavenging ability. Therefore, it is expected that the ethyl acetate fraction of the hemp root extract will additionally contribute to the antidiabetic activity by exhibiting excellent antioxidant and carcinogenic activity.
실시예 5: 대마 뿌리 에탄올 추출물의 순차적 유기용매 분획물의 항당뇨 활성 Example 5: Antidiabetic Activity of Sequential Organic Solvent Fractions of Hemp Root Ethanol Extract
실시예 4에서 조제된 대마 뿌리 추출물의 순차적 유기용매 분획물의 항당뇨 활성을 실시예 2의 방법과 동일하게 평가하였으며, 그 결과는 표 5에 나타내었다. The antidiabetic activity of the sequential organic solvent fractions of the hemp root extract prepared in Example 4 was evaluated in the same manner as in Example 2, and the results are shown in Table 5.
[표 5] 대마 뿌리 추출물의 순차적 유기용매 분획물의 항당뇨 활성[Table 5] Antidiabetic activity of sequential organic solvent fractions of hemp root extract
표 5에 나타낸 바와 같이, 대마 뿌리 추출물의 분획물은 0.5mg/ml 농도에서 양호한 α-glucosidase 저해활성을 보였으며, 특히, 헥센 분획물과 에틸아세테이트 분획물은 각각 15.3% 및 12.5%의 저해를 보여 에탄올 추출물보다 2.0~2.5배 강력한 항당뇨 활성을 나타내었으며, 이러한 항당뇨 활성은 농도의존적으로 나타났다. As shown in Table 5, the fraction of the hemp root extract showed good α-glucosidase inhibitory activity at a concentration of 0.5 mg/ml. In particular, the hexene fraction and the ethyl acetate fraction showed inhibition of 15.3% and 12.5%, respectively, and the ethanol extract It exhibited 2.0-2.5 times stronger antidiabetic activity, and this antidiabetic activity was concentration-dependent.
실시예 6: 대마 뿌리 에탄올 추출물의 활성 분획물의 인간 적혈구 용혈 활성Example 6: Human Erythrocyte Hemolytic Activity of Active Fractions of Hemp Root Ethanol Extract
대마 뿌리의 경우, 한방에서 마자근으로 불리며 통풍, 통증, 염증, 피부 화상, 구토, 감염, 성병 치료 등 다양한 약용 용도로 사용되어 왔다. 그러나, 대마 뿌리 추출물의 분획물들에 대한 안전성이 객관적으로 평가된 바 없으므로 이들 분획물의 급성독성 가능성을 평가하기 위해 인간 적혈구 용혈 활성을 실시예 3의 방법으로 평가하였다.In the case of hemp root, it is called jaja root in oriental medicine and has been used for various medicinal purposes such as gout, pain, inflammation, skin burns, vomiting, infection, and treatment of sexually transmitted diseases. However, since the safety of the fractions of the hemp root extract has not been objectively evaluated, the hemolytic activity of human erythrocytes was evaluated by the method of Example 3 to evaluate the acute toxicity potential of these fractions.
[표 6] 대마 뿌리 추출물의 활성 분획물의 인간 적혈구 용혈 활성[Table 6] Human erythrocyte hemolytic activity of active fractions of hemp root extract
표 6에 나타낸 바와 같이, 대조구로 사용된 DMSO와 물은 용혈 활성이 없었으며, triton X-100은 1mg/ml 농도에서 적혈구를 100% 용혈시킴을 확인하였다. 또한, 항암제, 항진균제로 사용되고 있는 amphotericin B의 경우 0.025mg/ml 농도에서 50% 이상 적혈구를 용혈시킴을 확인하였다. As shown in Table 6, DMSO and water used as controls had no hemolytic activity, and it was confirmed that triton X-100 hemolyzed red blood cells 100% at a concentration of 1 mg/ml. In addition, in the case of amphotericin B, which is used as an anticancer agent and antifungal agent, it was confirmed that more than 50% of red blood cells were hemolyzed at a concentration of 0.025 mg/ml.
한편, 대마 뿌리 추출물 및 이의 에틸아세테이트 분획물, 부탄올 분획물 및 물 잔류물은 1mg/ml 농도까지 전혀 적혈구 용혈현상이 나타나지 않아 급성독성 및 적혈구 용혈 활성은 없음을 확인하였고, 대마 뿌리 추출물의 헥센 분획물은 1mg/ml 농도에서 17.2%의 비교적 낮은 용혈활성을 확인하였다. 이러한 결과는 본 발명의 대마 뿌리 에탄올 추출물의 헥센 분획물과 에틸아세테이트 분획물이 용혈 활성이 없거나 미약하여 아스피린과 같은 부작용이 나타나는 항혈전제를 안전하게 대치할 수 있음을 제시하고 있다. On the other hand, the hemp root extract and its ethyl acetate fraction, butanol fraction and water residue did not show any red blood cell hemolysis at a concentration of 1 mg/ml, confirming that acute toxicity and hemolytic activity were absent. The hexene fraction of the hemp root extract was 1 mg A relatively low hemolytic activity of 17.2% was confirmed at the /ml concentration. These results suggest that the hexene fraction and the ethyl acetate fraction of the hemp root ethanol extract of the present invention can safely replace antithrombotic agents that have side effects such as aspirin because they have no or weak hemolytic activity.
실시예 7: 대마 뿌리 에탄올 추출물 및 이의 활성 분획물의 혈장, 산 및 열 안정성 평가 Example 7: Evaluation of Plasma, Acid and Thermal Stability of Hemp Root Ethanol Extract and its Active Fraction
상기 실시예 1 및 4에서 얻은 대마 뿌리 에탄올 추출물과 이의 헥센 분획물 및 에틸아세테이트 분획물을 대상으로 항당뇨 활성에 대한 혈장 안정성, 열 안정성 및 산 안정성을 확인하였다. 상기 추출물 및 분획물들은 100℃에서 1시간 열 처리, pH 2(0.01M HCl)에서의 1시간 처리, 혈장에서 1시간 처리시에도 α-glucosidase 저해활성의 감소가 나타나지 않았다. 따라서, 대마 줄기 에탄올 추출물 및 이의 헥센 분획물과 에틸아세테이트 분획물은 내산성, 내열성을 가진 항당뇨 활성 물질을 포함하고 있음을 확인하여 실제적 이용 가능성이 높다고 판단하였다.Plasma stability, thermal stability, and acid stability for antidiabetic activity were confirmed for the hemp root ethanol extract, hexene fraction, and ethyl acetate fraction obtained in Examples 1 and 4 above. The extracts and fractions did not show any decrease in α-glucosidase inhibitory activity even after 1 hour heat treatment at 100° C., 1 hour treatment at pH 2 (0.01 M HCl), and 1 hour treatment in plasma. Therefore, it was confirmed that the hemp stem ethanol extract and its hexene fraction and ethyl acetate fraction contained an antidiabetic active substance having acid resistance and heat resistance, and thus it was judged that the practical use was high.
<연구 과제><Research Project>
본 발명의 모든 내용은 아래 연구과제의 연구 성과임을 확인합니다.It is confirmed that all contents of the present invention are the research results of the following research projects.
과제번호: 2020-0250Assignment number: 2020-0250
주관 : 안동시청Organizer: Andong City Hall
연구관리전문기관 : 안동대학교 산학협력단Research management institution: Andong University Industry-University Cooperation Foundation
연구과제명 : 안동대마(Hemp)상용화를 위한 연구용역Research project name: Research service for commercialization of Andong hemp (Hemp)
기여율 : 100%Contribution rate: 100%
연구기간 : 2020. 6. 12 ~ 2021. 1. 11Research period: 2020. 6. 12 ~ 2021. 1. 11
주관기관 : 안동대학교 Organized by : Andong University
실제 연구수행기관 : 안동대학교 식품영양학과 Actual research institute: Department of Food and Nutrition, Andong University
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| De Angelis et al., 2014, PLoS One, 29;9(9):e108282 |
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