KR20190110206A - Phamaceutical composition for prevention or treatment of thrombosis comprising kyung-ok-go adding the silk of zea mays and pumpkin and health functional food comprising the same - Google Patents

Phamaceutical composition for prevention or treatment of thrombosis comprising kyung-ok-go adding the silk of zea mays and pumpkin and health functional food comprising the same Download PDF

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KR20190110206A
KR20190110206A KR1020180031858A KR20180031858A KR20190110206A KR 20190110206 A KR20190110206 A KR 20190110206A KR 1020180031858 A KR1020180031858 A KR 1020180031858A KR 20180031858 A KR20180031858 A KR 20180031858A KR 20190110206 A KR20190110206 A KR 20190110206A
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손호용
이만효
강석문
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재단법인 경북바이오산업연구원
안동대학교 산학협력단
경옥삼보 주식회사 농업회사법인
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Abstract

The present invention relates to a use of a restorative herb medicine prepared by adding Silk of Zea mays Linne and Cucurbita moschata. More specifically, the present invention relates to a pharmaceutical composition and health functional food for preventing or treating/ameliorating thrombosis through strong blood coagulation enzyme/factor inhibiting activity and platelet aggregation inhibiting activity by adding Silk of Zea mays Linne and Cucurbita moschata to an existing restorative herb medicine comprising Rehmannia glutinosa var. purpurea, Poria cocos, ginseng and honey as main ingredients. As being proved through an embodiment of the present specification, a restorative herb medicine having a Silk of Zea mays Linne and Cucurbita moschata as an active ingredient of a pharmaceutical composition and health functional food of the present invention: has excellent appealability by adding Silk of Zea mays Linne and Cucurbita moschata; exhibits strong antithrombotic activity by inhibiting thrombogenesis-related enzymes and blood coagulation factors; does not show hemolytic activity to human red blood cells at all; has excellent thermal stability; and does not exhibit loss in effects of inhibiting the thrombogenesis-related enzymes and the blood coagulation factors even at an acidic condition of pH 2 and within blood plasma at the same time such that the present invention is expected to be used for prevention and treatment of thrombosis such as ischemic stroke and hemorrhagic stroke through improvement of blood circulation. In addition, the active ingredient is processed into various forms such as extract, powder, pill, tablet, and the like to be taken at any time. Accordingly, the present invention is extremely useful in pharmaceutical and food industries.

Description

옥미수·호박 가미 경옥고를 유효성분으로 함유하는 혈전증의 예방 또는 치료용 약학적 조성물 및 건강 기능 식품{PHAMACEUTICAL COMPOSITION FOR PREVENTION OR TREATMENT OF THROMBOSIS COMPRISING KYUNG-OK-GO ADDING THE SILK OF ZEA MAYS AND PUMPKIN AND HEALTH FUNCTIONAL FOOD COMPRISING THE SAME}PHARMACEUTICAL COMPOSITION FOR PREVENTION OR TREATMENT OF THROMBOSIS COMPRISING KYUNG-OK-GO ADDING THE SILK OF ZEA MAYS AND PUMPKIN AND HEALTH FUNCTIONAL FOOD COMPRISING THE SAME}

본 발명은 옥미수(Silk of Zea mays Linne) 및 호박(Cucurbita moschata)을 가미하여 제조되는 경옥고의 용도에 관한 것으로서, 보다 상세하게는, 기존 생지황, 백복령, 인삼 및 벌꿀을 주성분으로 하는 경옥고에 옥미수와 호박을 가미하여 강력한 혈액 응고 효소/인자 저해 활성 및 혈소판 응집 저해 활성을 통한 혈전증의 예방 또는 치료/개선용 약학적 조성물 및 건강 기능 식품에 관한 것이다.The present invention is a silk of Zea mays Linne and Cucurbita Moschata ) relates to the use of jadeite oak prepared with the addition of oxime water and zucchini in addition to jadeite and zucchini, the main ingredient of which is the raw raw sulfur, baekbokyeong, ginseng and honey, and a strong blood coagulation enzyme / factor inhibitory activity and platelets. The present invention relates to a pharmaceutical composition for the prevention or treatment / improvement of thrombosis through agglutination inhibitory activity and a dietary supplement.

인체 구성 성분으로서의 혈액은 산소, 영양분, 노폐물의 운반 기능과 완충 작용, 체온 유지, 삼투압 조절 및 이온 평형 유지, 수분 일정 유지, 액성 조절 작용, 혈압의 유지 및 조절, 생체 방어 등 다양한 중요 기능들을 가지고 있다. 정상적인 혈액 순환은 체내에서의 혈액 응고 반응계와 혈전 용해 반응계가 상호 보완적으로 조절되면서 혈액 순환을 용이하게 하며, 이들 중 혈액 응고 반응계의 기작은 혈관벽에 혈소판이 점착, 응집하여 혈소판 혈전을 형성한 후, 혈액 응고계가 활성화되어 혈소판 응집괴를 중심으로 피브린 혈전이 형성되는 것으로 보고되어 있다. Blood as a human component has various important functions such as transporting and buffering oxygen, nutrients, and wastes, maintaining body temperature, controlling osmotic pressure and ion balance, maintaining moisture, controlling fluid, maintaining and regulating blood pressure, and defending the body. have. Normal blood circulation facilitates blood circulation as the blood coagulation reaction system and the thrombolytic reaction system in the body are complementarily regulated. Among them, the mechanism of the blood coagulation reaction system forms platelet thrombus due to the adhesion of platelets to the blood vessel walls and aggregation. In addition, it has been reported that the blood coagulation system is activated to form fibrin clots around platelet aggregates.

한편, 피브린 혈전의 생성은 수많은 혈액 응고 인자들의 여러 단계 반응을 거쳐 피브린 응고에 관여하는 트롬빈이 활성화되어, 최종적으로 피브리노겐으로부터 피브린 단량체를 생성하게 하며, 피브린 단량체들은 칼슘에 의해 중합되어, 혈소판과 내피세포에 결합하게 되며 XIII 인자에 의해 교차 결합된 피브린 폴리머를 형성하면서 영구적인 혈전을 생성하게 된다. 또한, 트롬빈은 혈소판, V 인자, VII 인자들을 활성화시켜 혈액 응고 반응을 촉진시키는 등 혈전 생성에 중추적 역할을 하게 된다. 따라서, 트롬빈의 활성 저해물질은 과다한 혈액 응고 이상으로 발생하는 다양한 혈전성 질환에 매우 유용한 예방 및 치료제로 사용될 수 있다. 한편, 내인성 혈전 생성 경로에는 XII 인자, XI 인자, XII 인자, IX 인자, X 인자의 순차적 활성화에 이은 프로트롬빈의 활성화가 최종적으로 트롬빈을 활성화하는 것으로 알려져 상기의 혈액 응고 인자의 특이적 저해 역시 중요한 혈전성 질환 치료제의 개발 타겟이 되고 있으며, 외인성 혈전 생성경로의 경우, II 인자(prothrombin), V 인자, VII 인자, X 인자의 활성화에 따른 혈전생성이 알려져 있다. 현재까지, 혈전성 질환의 예방과 치료에 헤파린, 쿠마린, 아스피린, 유로키네이즈 등의 다양한 항응고제, 항혈소판제, 혈전용해제 등이 사용되고 있으나, 이들은 가격이 매우 높을 뿐 아니라, 출혈성 부작용과 위장 장해 및 과민 반응 등으로 그 사용이 한정되고 있는 실정이다. On the other hand, the generation of fibrin thrombus is a multi-step reaction of numerous blood coagulation factors that activates thrombin, which is involved in fibrin coagulation, and finally generates fibrin monomers from fibrinogen, and the fibrin monomers are polymerized by calcium, thereby forming platelets and endothelial cells. It binds to cells and creates permanent thrombi, forming fibrin polymers cross-linked by factor XIII. In addition, thrombin plays a pivotal role in thrombus formation by activating platelets, factor V and factor VII to promote blood coagulation. Therefore, thrombin activity inhibitors can be used as a prophylactic and therapeutic agent that is very useful for various thrombotic diseases that occur due to excessive blood clotting. On the other hand, in the endogenous thrombus generation pathway, sequential activation of factor XII, factor XI, factor XII, factor IX and factor X is followed by activation of prothrombin to finally activate thrombin. It has been a development target for the treatment of sexual diseases, and in the case of exogenous thrombus generation pathway, thrombus generation is known according to the activation of factor II (prothrombin), factor V, factor VII, and factor X. To date, various anticoagulants such as heparin, coumarin, aspirin, urokinase, antiplatelet agents, thrombolytic agents, etc. have been used for the prevention and treatment of thrombotic diseases, but they are very expensive and have hemorrhagic side effects, gastrointestinal disorders and hypersensitivity. The use is limited by reaction etc.

경옥고는 인삼, 복령, 생지황, 꿀 등을 구성생약으로 하는 고형제제로 동의보감과 방약합편에 처방과 제법이 수제된 보혈강장제로, 민간에서도 허약체질 개선보약으로 널리 사용하여 왔다. 경옥고는 백삼과 백복령 분말에 생지황즙과 꿀을 넣어 장시간 가열하여 만든 고형제품으로 동의보감에 의하면 '정과 수를 채워주고 진기를 고르게 하며, 원기를 보하며 늙은이를 젊어지게 하고 모든 허손증을 보하며 온갖 병을 낫게 한다. 또 정신이 좋아지고 오장이 충실해지며, 흰머리가 다시 검어지고 빠진 이가 다시 나오면 걸음걸이가 뛰는 말과 같이 빨라지고, 하루에 두세 번 먹으면 종일토록 배고프거나 목이 마르는 일이 없다'로 기재되어 있다. 그러나, 경옥고는 원료를 혼합한 후 중탕 가열하여 고형제품으로 만드는 것으로, 제조방법이 복잡하면서 장시간의 노력이 필요한 문제점을 가지고 있으며, 쓴맛과 이취로 기호성이 낮은 문제가 있다. Gyeongokgo is a solid preparation that consists of ginseng, Bokryeong, Saenghwanghwang, honey, etc. as a constituent herbal medicine. Gyeongokgo is a solid product made by heating raw ginseng juice and honey in white ginseng and baekbokryeong powder and heating it for a long time. According to Dongbogam, 'filling tablets and water, leveling the essence, refreshing the old man, relieving the old man and all kinds of diseases To heal. In addition, the spirit is improved, the five intestines are faithful, and the gray hair is black again, and the missing person comes out again like a walking horse, and if you eat two or three times a day, you are not hungry or thirsty all day long. However, jadeite is a solid product by mixing the raw materials and heated in a hot water bath, the manufacturing method is complicated and has a problem that requires a long time, there is a problem of low palatability due to bitter taste and odor.

현재까지 경옥고와 관련된 연구는 경옥고 자체의 유용 활성 평가 및 천연물을 가미한 가미경옥고의 효능, 발효시킨 경옥고의 효능 등에 대해 집중되어 있으며, 유용 생리활성으로 면역 증강활성(이가순 외, 2013, 한국식품영양과학회지 42: 335-341), 항 피로효과(김준호, 2011, 원광대학교 박사논문; 김용안 외, 2016, 생약학회지 47: 258-263), 고혈당, 고혈압 및 염증, 위궤양 등에 대한 경옥고의 생리활성(황완균 외, 1994, 생약학회지 25: 51-58), 항치매 효과(신범영, 2011. 경희대학교 박사논문) 등에 대한 보고가 있으며, 다양한 경옥고의 항산화 효과 비교(이소연 외, 2008, The Korea journal of herbology 23: 123-136)도 이루어져 있으며, 하수오 가미 경옥고의 양모 효과(도은주 외, 2011. The Korea journal of herbology 26: 9-14)도 알려져 있다. 최근에는 경옥고를 이용한 음료(권세욱 외, 2013, 동의생리병리학회지 27: 233-238) 및 경옥고 식초 제조(박성민 외, 2009, Herbal formula science 17: 121-128)도 보고된 바 있다. Until now, researches related to jadeite have concentrated on the evaluation of useful activity of jadeite itself, the efficacy of Kamigonoe added with natural products, and the effect of fermented jadeite, and its useful physiological activity to enhance immune activity (Lee Ga-soon et al., 2013, Korea Food and Nutrition Division). 42: 335-341), Anti-Fatigue Effect (Jun Ho Kim, 2011, Ph.D., Wonkwang University; Ph.D., 2016, Korean Journal of Pharmacognosy 47: 258-263), Physiological Activity of Kyung-gogo on Hyperglycemia, Hypertension and Inflammation, and Gastric Ulcer Et al., 1994, Korean Journal of Pharmacognosy 25: 51-58), anti-dementia effects (Shin Beom-young, 2011. Kyung Hee University, Ph.D. dissertation), etc., and comparison of the antioxidant effects of various jadeite (Seoyeon Lee, 2008, The Korea journal of herbology 23 : 123-136), and the wool effect of sewage gill jadeite (Do Eun-ju et al., 2011. The Korea journal of herbology 26: 9-14). Recently, beverages using jadeite (Kwon, Se-Wook et al., 2013, Journal of Oriental Physiology and Pathology 27: 233-238) and the manufacture of jadeite vinegar (Seong-Min Park, 2009, Herbal formula science 17: 121-128) have been reported.

한편, 경옥고와 관련된 특허로는, 인삼, 복령, 생지황, 꿀을 주재료로 하는 원방 경옥고의 효율적인 제조 및 흡수 증대에 관한 특허, 원방 경옥고에 다양한 천연물, 한방재료를 가미하여 기능성과 기호성을 강화시킨 경옥고 제조에 관한 특허 및 다양한 경옥고를 섭취하기 쉽도록 음료, 플레이크, 양갱, 초콜릿 등으로 제조하는 기호성과 접근성을 증대시킨 특허로 대별할 수 있다. 먼저, 경옥고 제조 및 흡수 증대와 관련하여, 대한민국 등록특허 제10-1725187호에 경옥고 흡수를 용이하게 하기 위한 작은 입자를 가진 [경옥고의 제조방법 및 이에 따라 제조된 경옥고], 대한민국 등록특허 제10-1441744호에 미생물 발효를 통해 아미노산 함량을 증가시키는 [미생물을 이용한 발효경옥고 제조방법]이 개시되어 있으며, 다음으로, 기능성과 기호성을 증대시킨 가미경옥고와 관련하여, 대한민국 등록특허 제10-1781432호에 원방 경옥고에 단삼, 황기, 산사, 맥아 추출물을 포함하는 [약용 작물로 이루어진 고지혈증 개선용 건강식품 및 이에 의해 제조된 경옥고], 대한민국 등록특허 제10-1682637호에 기억력 개선효과가 우수한 청피를 포함하는 [청피경옥고를 유효성분으로 포함하는 신경세포보호 및 기억력개선효과를 갖는 약학 조성물 및 청피경옥고를 함유하는 기능성식품], 대한민국 등록특허 제10-1514041호에 산양삼을 첨가하여 기호도와 저장성이 우수한 [산양삼 경옥고 및 이의 제조방법], 대한민국 등록특허 제10-1198211호에 [해삼을 이용한 경옥고의 제조방법], 대한민국 등록특허 제10-1060309호에 대추를 첨가하여 관능성을 증대시킨 [대추 경옥고], 대한민국 등록특허 제10-1016195호에 천마를 첨가하여 식감과 기호성을 증대시킨 [천마경옥고 및 그 제조방법]이 개시되어 있다. 마지막으로, 경옥고를 접근성이 우수한 다양한 제품으로 제조하는 특허와 관련하여, 대한민국 등록특허 제10-1716005호에 구성 성분의 분말화로 경옥고 효능을 증대시키는 산제의 [활성성분을 다량 함유한 경옥고 산제의 제조방법], 대한민국 등록특허 제10-1454729호에 쉽게 섭취가 가능한 [활성성분을 다량 함유한 경옥고 플레이크 스낵의 제조방법], 대한민국 등록특허 제10-1404520호에 [천마경옥고를 이용한 초콜릿의 제조방법 및 상기 방법으로 제조된 초콜릿], 대한민국 등록특허 제10-0286390호에 [양갱형 경옥고 제조방법 및 그 경옥고], 대한민국 등록특허 제10-0354962호에 쉽게 섭취가 가능한 [경옥고 즉석차 및 그 제조방법], 대한민국 등록특허 제10-1153426호에 [경옥고를 이용한 음료 조성물의 제조방법 및 이를 이용한 음료 조성물]이 개시되어 있다.On the other hand, patents related to jadeite are patents related to efficient manufacture and absorption of distant jadeite, whose main ingredients are ginseng, bokyeong, raw jihwang, and honey, and jadeite which enhances functionality and palatability by adding various natural products and herbal materials to distant jadeite. Patents related to manufacturing and patents that enhance the palatability and accessibility of manufacturing various beverages, flakes, yokan, chocolate, etc. to facilitate the ingestion of various jadeite can be classified. First, in relation to the manufacture of jadeite and the increase in absorption, Korean Patent No. 10-1725187 discloses [method of preparing jadeite and jadeite prepared accordingly] having small particles for facilitating absorption of jadeite. No. 1441744 discloses a method for producing fermented crypts using microorganisms to increase the amino acid content through fermentation of microorganisms. Next, in connection with the scavenging crypts having increased functionality and palatability, Korean Patent No. 10-1781432 Far-gyeonggogo in the health food for improving hyperlipidemia comprising medicinal crops, including Dansam, Astragalus, hawthorn, malt extract, and Kyungokgo prepared by it; Korean Patent No. 10-1682637, which contains excellent skin improvement effect [Pharmaceutical composition and cheongpi jadeite containing neuronal cell protection and memory improvement effect Functional Food Containing], Addition of Goyang Ginseng to Korean Patent No. 10-1514041 [Gangok Ginseng and its manufacturing method] excellent in palatability and shelf life, Korean Patent No. 10-1198211 No. Method], [jujube gyeongokgo] by adding jujube to the Republic of Korea Patent No. 10-1060309 to increase the functionality of the jujube; Manufacturing method] is disclosed. Lastly, in relation to the patent for manufacturing jadeite into various products having excellent accessibility, Korean Patent No. 10-1716005 discloses the preparation of jadeite powder containing a large amount of active ingredient of powder to increase jadeite efficacy by powdering of components. Method], Republic of Korea Patent No. 10-1454729 [Easily ingested [Method of manufacturing a kyungok flake snack containing a large amount of active ingredient], Republic of Korea Patent No. 10-1404520 [Method of manufacturing chocolate using cheonma gyeonggo and Chocolate manufactured by the above method, Korean Patent No. 10-0286390 [Yangok-type jadeite manufacturing method and its jadeokgo], Republic of Korea Patent No. 10-0354962 can easily be ingested [Gyeongokgo instant tea and its manufacturing method] , Republic of Korea Patent No. 10-1153426 discloses a method for preparing a beverage composition using a jade jade and a beverage composition using the same.

KRKR 10-119821110-1198211 BB KRKR 10-106030910-1060309 BB KRKR 10-101619510-1016195 BB

황완균 외, 1994, 생약학회지 25: 51-58 Wan-Kyun Hwang et al., 1994, Korean Journal of Pharmacognosy 25: 51-58

본 발명은 상기와 같은 종래 기술의 문제점을 해결하기 위하여 안출된 것으로서, 본 발명에서 해결하고자 하는 과제는 기존 원방 경옥고에 옥미수 및 호박을 가미하여 옥미수와 호박이 가미된 경옥고 조성물을 제조하고, 상기 경옥고 조성물의 강력한 혈액 응고 효소/인자 저해 활성 및 혈소판 응집 저해 활성을 이용하여 상기 조성물을 혈전증의 예방 또는 치료/개선용 약학적 조성물 및 건강 기능 식품으로 제공하고자 하는 것이다.The present invention has been made in order to solve the problems of the prior art as described above, the problem to be solved in the present invention is to prepare a jadeite composition with the addition of jade water and amber by adding jade water and amber to the existing distant jadeite, By using the potent blood coagulation enzyme / factor inhibitory activity and platelet aggregation inhibitory activity of the jadeite composition to provide the composition as a pharmaceutical composition and health functional food for the prevention or treatment / improvement of thrombosis.

상기와 같은 과제를 해결하기 위하여, 본 발명은 인삼 100중량부에 대하여, 백복령 80~120중량부, 생지황 350~450중량부, 벌꿀 350~450중량부, 옥미수 1,500~1,800중량부 및 호박 600~800중량부를 혼합, 가열 추출, 여과 및 농축하여 제조되는 옥미수·호박 가미 경옥고를 유효성분으로 함유하는 혈전증의 예방 또는 치료용 약학적 조성물을 제공한다.In order to solve the above problems, the present invention with respect to 100 parts by weight of ginseng, 80 to 120 parts by weight of Baekbokyeong, 350 to 450 parts by weight of raw turmeric, 350 to 450 parts by weight of honey, 1,500 to 1,800 parts by weight of jade and pumpkin 600 Provided is a pharmaceutical composition for the prevention or treatment of thrombosis, which comprises jade water, pumpkin amber jadeite jadeite prepared by mixing, heating extraction, filtration and concentration as an active ingredient.

또한, 본 발명은 인삼 100중량부에 대하여, 백복령 80~120중량부, 생지황 350~450중량부, 벌꿀 350~450중량부, 옥미수 1,500~1,800중량부 및 호박 600~800중량부를 혼합, 가열 추출, 여과 및 농축하여 제조되는 옥미수·호박 가미 경옥고를 유효성분으로 함유하는 혈액 응고 저해제를 제공한다.In addition, the present invention is mixed with 100 to 100 parts by weight of ginseng, 80 to 120 parts by weight of Baekbokryeong, 350 to 450 parts by weight of raw sulfur, 350 to 450 parts by weight of honey, 1,500 to 1,800 parts by weight of jade and 600 to 800 parts by weight of pumpkin Provided is a blood coagulation inhibitor containing jade water, pumpkin amber jadeite jadeite prepared by extraction, filtration and concentration as an active ingredient.

또한, 본 발명은 인삼 100중량부에 대하여, 백복령 80~120중량부, 생지황 350~450중량부, 벌꿀 350~450중량부, 옥미수 1,500~1,800중량부 및 호박 600~800중량부를 혼합, 가열 추출, 여과 및 농축하여 제조되는 옥미수·호박 가미 경옥고를 유효성분으로 함유하는 혈전증의 예방 또는 개선용 건강 기능 식품을 제공한다.In addition, the present invention is mixed with 100 to 100 parts by weight of ginseng, 80 to 120 parts by weight of Baekbokryeong, 350 to 450 parts by weight of raw sulfur, 350 to 450 parts by weight of honey, 1,500 to 1,800 parts by weight of jade and 600 to 800 parts by weight of pumpkin Provided is a health functional food for the prevention or improvement of thrombosis, which contains jade water, pumpkin kamikaze jadeite, which is produced by extraction, filtration and concentration as an active ingredient.

본 발명의 약학적 조성물 및 건강 기능 식품의 유효성분으로서의 옥미수와 호박이 가미된 경옥고는, 본 명세서의 실시예를 통해 증명된 바와 같이, 옥미수 및 호박이 가미되어 관능성이 우수하면서 혈전 생성 관련 효소 저해 및 혈액 응고 인자의 저해에 의한 강력한 항혈전 활성을 나타냄과 동시에, 인간 적혈구에 대한 용혈 활성을 전혀 나타내지 않고, 열 안정성이 우수하고, pH 2의 산성 조건 및 혈장 내에서도 혈전 생성 관련 효소 및 혈액 응고인자 저해 효과의 손실이 나타나지 않으므로, 혈행 개선을 통해 허혈성 뇌졸중 및 출혈성 뇌졸중과 같은 혈전증의 예방 및 치료용으로 사용할 수 있을 것으로 기대되며, 상기 유효성분은 추출액, 분말, 환, 정 등의 다양한 형태로 가공되어 상시 복용이 가능한 형태로 조제할 수 있는 뛰어난 효과가 있으므로 제약 산업 및 식품 산업상 매우 유용한 발명인 것이다.As the active ingredient of the pharmaceutical composition and health functional food of the present invention, jadeite and zucchini added jadeite, as demonstrated through the examples of the present specification, jadeite and amber are added to have excellent functionality and generate thrombus It exhibits strong antithrombotic activity by inhibition of related enzymes and blood coagulation factor, shows no hemolytic activity against human erythrocytes, excellent thermal stability, enzymes related to thrombus generation in acidic conditions and plasma of pH 2 and Since there is no loss of the blood coagulation factor inhibitory effect, it is expected that it can be used for the prevention and treatment of thrombosis such as ischemic stroke and hemorrhagic stroke by improving blood circulation. It is processed in the form and can be prepared in a form that can be taken at all times. The industry and the food industry will be very useful inventions.

도 1은 본 발명의 옥미수·호박 가미 경옥고의 인간 혈소판 응집저해 활성을 나타낸 것이다. 1: 용매 대조구(물), 2: 아스피린(0.25mg/ml), 3: 아스피린(0.125mg/ml), 4: 기존 경옥고(6.5mg/ml), 5: 옥미수·호박 가미 경옥고(6.5mg/ml). Figure 1 shows the human platelet aggregation inhibitory activity of chalcedony amber gourd amber jadeite of the present invention. 1: solvent control (water), 2: aspirin (0.25 mg / ml), 3: aspirin (0.125 mg / ml), 4: conventional jadeite (6.5 mg / ml), 5: jade water, pumpkin amber jadeite (6.5 mg) / ml).

이하, 본 발명을 상세하게 설명한다.EMBODIMENT OF THE INVENTION Hereinafter, this invention is demonstrated in detail.

본 발명의 발명자들은 혈액 순환 기능을 개선시키는데 도움이 되는 경옥고를 제조하기 위하여, 다양한 천연물을 첨가한 가미 경옥고를 제조하던 중, 옥미수와 호박을 가미하여 제조되는 경옥고가 항혈전 활성이 매우 우수함을 확인하였다. 본 발명의 발명자들은, 다양한 비율의 옥미수와 호박을 기존 경옥고에 가미하여 옥미수·호박 가미 경옥고의 첨가 비율을 결정하였으며, 이후, 기존 경옥고와 비교하여 이화학적 특성, 유용성분 함량 분석 및 항혈전 활성을 평가하였다. 상기 옥미수와 호박이 가미된 경옥고는 인간 적혈구에 대해 용혈 활성은 전혀 나타내지 않으면서도, 열 안정성과 산 안정성이 우수한 특징을 가짐을 확인함으로써 "옥미수·호박 가미 경옥고"를 혈전증의 예방 또는 치료/개선용 약학적 조성물 및 건강 기능 식품으로 활용하고자 하였다. The inventors of the present invention, while preparing a jadeite jade added to various natural products in order to prepare a jadeite which helps to improve blood circulation function, jadeite prepared by adding jade water and amber is very good anti-thrombotic activity Confirmed. The inventors of the present invention determined the addition ratio of jade water and pumpkin amber jadeite by adding various ratios of jade water and pumpkin to the existing jadeite, and then, compared with the existing jadeite, physicochemical properties, useful component content analysis and antithrombosis Activity was evaluated. The jadeite and amber jadeite added to the erythrocytes of human erythrocytes, while showing no hemolytic activity at all, and excellent thermal stability and acid stability by confirming that "Omisu, zucchini jadeite jade" to prevent or treat thrombosis / To improve the pharmaceutical composition and health functional food.

따라서, 본 발명은 인삼 100중량부에 대하여, 백복령 80~120중량부, 생지황 350~450중량부, 벌꿀 350~450중량부, 옥미수 1,500~1,800중량부 및 호박 600~800중량부를 혼합, 가열 추출, 여과 및 농축하여 제조되는 옥미수·호박 가미 경옥고를 유효성분으로 함유하는 혈전증의 예방 또는 치료용 약학적 조성물을 제공한다.Therefore, the present invention is mixed with 100 to 100 parts by weight of ginseng, 80 to 120 parts by weight of Baekbokyeong, 350 to 450 parts by weight of raw sulfur, 350 to 450 parts by weight of honey, 1,500 to 1,800 parts by weight of jade and 600 to 800 parts by weight of pumpkin Provided is a pharmaceutical composition for the prevention or treatment of thrombosis, which contains jade water, pumpkin amber jadeite jadeite, which is prepared by extraction, filtration and concentration as an active ingredient.

또한, 본 발명은 인삼 100중량부에 대하여, 백복령 80~120중량부, 생지황 350~450중량부, 벌꿀 350~450중량부, 옥미수 1,500~1,800중량부 및 호박 600~800중량부를 혼합, 가열 추출, 여과 및 농축하여 제조되는 옥미수·호박 가미 경옥고를 유효성분으로 함유하는 혈액 응고 저해제를 제공한다.In addition, the present invention is mixed with 100 to 100 parts by weight of ginseng, 80 to 120 parts by weight of Baekbokryeong, 350 to 450 parts by weight of raw sulfur, 350 to 450 parts by weight of honey, 1,500 to 1,800 parts by weight of jade and 600 to 800 parts by weight of pumpkin Provided is a blood coagulation inhibitor containing jade water, pumpkin amber jadeite jadeite prepared by extraction, filtration and concentration as an active ingredient.

또한, 본 발명은 인삼 100중량부에 대하여, 백복령 80~120중량부, 생지황 350~450중량부, 벌꿀 350~450중량부, 옥미수 1,500~1,800중량부 및 호박 600~800중량부를 혼합, 가열 추출, 여과 및 농축하여 제조되는 옥미수·호박 가미 경옥고를 유효성분으로 함유하는 혈전증의 예방 또는 개선용 건강 기능 식품을 제공한다.In addition, the present invention is mixed with 100 to 100 parts by weight of ginseng, 80 to 120 parts by weight of Baekbokryeong, 350 to 450 parts by weight of raw sulfur, 350 to 450 parts by weight of honey, 1,500 to 1,800 parts by weight of jade and 600 to 800 parts by weight of pumpkin Provided is a health functional food for the prevention or improvement of thrombosis, which contains jade water, pumpkin kamikaze jadeite, which is produced by extraction, filtration and concentration as an active ingredient.

상기 옥미수·호박 가미 경옥고는 95℃에서 24~48시간 가열 추출하는 것이 바람직하며, 기호성을 증대시키기 위해 최종 당도를 25~30브릭스(brix)로 농축하는 것이 바람직하다. It is preferable to heat-extract 24 to 48 hours at 95 degreeC, and to concentrate the final sweetness to 25-30 brix in order to improve palatability.

바람직한 구체예로서, 본 발명의 옥미수·호박 가미 경옥고의 제조는 인삼 분말 3중량%, 백복령 분말 3중량%, 생지황 분말 12중량%, 벌꿀 12중량%, 옥미수 49중량% 및 호박 21중량%를 포함하는 혼합물을 제조하고, 상기 혼합물을 95℃에서 24~48시간 가열 추출하고, 이를 여과한 후, 26브릭스로 농축하여 제조될 수 있다. 농축액은 기존 경옥고보다 관능성이 매우 우수하였으며, 쓴맛과 시큼한 맛은 거의 느껴지지 않았다. As a preferred embodiment, the preparation of the chalcedony water of the present invention is made of 3% by weight of ginseng powder, 3% by weight of Baekbokryeong powder, 12% by weight of raw sulfur powder, 12% by weight of honey, 49% by weight of jade water and 21% by weight of pumpkin. To prepare a mixture comprising, the mixture is heat-extracted at 95 ℃ 24 ~ 48 hours, and after filtering it, it can be prepared by concentrating to 26 bricks. The concentrate was much more functional than conventional jadeite, and the bitter and sour taste was hardly felt.

위와 같이 제조된 본 발명의 옥미수·호박 가미 경옥고 조성물을 대상으로 항혈전 활성을 트롬빈 저해(Thrombin Time), 프로트롬빈 저해(Prothrombin Time) 및 혈액응고인자 저해(활성부분 트롬보플라스틴 타임, activated Partial Thromboplastin Time: aPTT) 및 혈소판 응집저해활성을 통하여 평가하였으며, 옥미수·호박 가미 경옥고는 기존 경옥고보다 매우 강력한 항응고 활성을 나타냄을 확인하였다. 또한, 인간 혈소판 응집저해 평가에서도, 옥미수·호박 가미 경옥고는 기존 경옥고와 유사한 응집활성을 나타내었다. 따라서, 옥미수·호박 가미 경옥고는 혈소판 응집 반응을 활성화 시키지 않으면서 혈전 생성을 강력하게 억제하여 혈액순환 개선에 기여함을 확인하였다. Antithrombotic activity of thrombin time, prothrombin time and blood coagulation factor inhibition (active part thromboplastin time, activated partial) Thromboplastin Time (aPTT) and platelet aggregation inhibitory activity was evaluated, and jade water, pumpkin kamikaze jadeite showed much stronger anticoagulant activity than conventional jadeite. In addition, in the evaluation of the inhibition of human platelet aggregation, jade water and zucchini-grilled jadeite showed similar coagulation activity as existing jadeite. Therefore, it was confirmed that jade water and pumpkin amber jadeite contributed to improving blood circulation by strongly inhibiting blood clot production without activating platelet aggregation reaction.

상기 바람직한 구체예로부터 제조된 옥미수·호박 가미 경옥고 조성물은 기존 경옥고와 유사한 당도를 나타내지만, 산도는 0.15%로, 기존 경옥고의 0.97~1.0%보다 낮아 관능성이 우수하였다. 또한, 기존 경옥고는 5% 농도(최종 농도 13mg/ml)에서 무첨가구에 비해 각각 1.74배, 1.00배, 1.59배 연장된 트롬빈 타임, 프로트롬빈 타임 및 에이피티 타임을 나타내어 미약한 항혈전 활성을 나타낸 반면, 옥미수·호박 가미 경옥고의 경우 5% 농도(최종 농도 13mg/ml)에서 무첨가구에 비해 각각 9.84배, 1.33배, 3.80배 연장된 트롬빈 타임, 프로트롬빈 타임 및 에이피티 타임을 나타내었다. 특히, 옥미수·호박 가미 경옥고는 7% 농도(최종 농도 18.2mg/ml)에서는 무첨가구에 비해 15배 이상 연장된 트롬빈 타임 및 에이피티 타임을 나타내었다. 또한, 옥미수·호박 가미 경옥고는 인간 적혈구에 대한 용혈활성을 나타내지 않아 급성독성을 유발하지 않음을 확인하였다. The jade water-pumpkin sapphire jadeite composition prepared from the above preferred embodiment exhibits a similar sugar content to the existing jadeite, but has an acidity of 0.15%, which is lower than 0.97-1.0% of the existing jadeite. In addition, the existing jadeite has a weak antithrombotic activity, showing 1.74 fold, 1.00 fold, 1.59 fold extended thrombin time, prothrombin time, and epitaxial time, respectively, at 5% concentration (final concentration 13 mg / ml). In the case of jade water and amber amber jadeite, the concentration of thrombin, prothrombin time, and epitaxial time were 9.84, 1.33, and 3.80 times longer than the non-added group, respectively, at 5% concentration (final concentration: 13 mg / ml). In particular, jade water and zucchini kelp jadeite showed thrombin time and apity time extended by more than 15 times at 7% concentration (final concentration 18.2mg / ml). In addition, it was confirmed that Okmisu-zucchini-grilled jadeite did not exhibit hemolytic activity against human red blood cells and did not cause acute toxicity.

본 발명의 조성물에 포함되는 옥미수·호박 가미 경옥고는 감압건조 및 동결건조, 또는 분무건조 등과 같은 통상적인 분말화 과정을 거쳐 분말로 제조될 수 있다. 옥미수·호박 가미 경옥고의 항혈전 활성 성분은 혈장 내의 다양한 분해 효소에 의하여 분해되지 않으며, 100℃의 열처리와 pH 2의 인체 위 내의 pH에서도 활성을 유지한다.The jade water, zucchini-flavored jadeite ointment included in the composition of the present invention may be prepared into a powder through a conventional powdering process such as reduced pressure drying and freeze drying or spray drying. The antithrombotic active ingredient of jade water and pumpkin amber jadeite is not decomposed by various degrading enzymes in plasma, and maintains its activity even at 100 ° C. heat treatment and pH 2 in the human stomach.

본 발명의 옥미수·호박 가미 경옥고는 혈전증과 관련된 다양한 질환들의 예방 또는 치료/개선용으로 사용될 수 있다. 상기 질환들은, 예를 들어, 동맥 혈전증으로서, 급성 심근 경색증, 가슴 통증, 호흡 곤란, 의식 소실, 허혈성 뇌졸중, 출혈성 뇌졸중, 두통, 운동 이상, 감각 이상, 성격 변화, 시력 저하, 간질 발작, 폐 혈전증, 심부정맥 혈전증, 하지 부종, 통증 및 급성 말초 동맥 폐쇄증 등을 들 수 있고, 정맥 혈전증으로서, 심부정맥 혈전증, 간문맥 혈전증, 급성 신장정맥 폐쇄증, 뇌 정맥동 혈전증 및 중심 망막정맥 폐쇄 등을 들 수 있다. The chalcedony amber amber of the present invention can be used for the prevention or treatment / improvement of various diseases related to thrombosis. The diseases are, for example, arterial thrombosis, acute myocardial infarction, chest pain, shortness of breath, loss of consciousness, ischemic stroke, hemorrhagic stroke, headache, dyskinesia, paresthesia, personality changes, decreased vision, epileptic seizures, pulmonary thrombosis , Deep vein thrombosis, lower extremity edema, pain, and acute peripheral arterial obstruction. Examples of venous thrombosis include deep vein thrombosis, portal vein thrombosis, acute renal vein occlusion, cerebral venous thrombosis, and central retinal vein occlusion.

바람직한 구체예로서, 본 발명의 옥미수·호박 가미 경옥고는 혈전증의 예방 또는 치료용 약학적 조성물의 용도로서 적용될 수 있다.As a preferred embodiment, the chalcedony amber water of the present invention can be applied as a use of a pharmaceutical composition for the prevention or treatment of thrombosis.

또한, 본 발명의 옥미수·호박 가미 경옥고는 혈액 응고 저해제 또는 항응고제의 약학적 용도로서 적용될 수 있다. In addition, the chalcedony amber gourd amber amber tiger'ogo of the present invention can be applied as a pharmaceutical use of a blood coagulation inhibitor or an anticoagulant.

상기 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. 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 be formulated in various forms such as powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols, oral formulations, injections of sterile injectable solutions, etc. It may be used orally or may be administered through various routes including intravenous, intraperitoneal, subcutaneous, rectal, topical, and the like. Such pharmaceutical compositions may further include carriers, excipients or diluents, and examples of suitable carriers, excipients or diluents that may be included include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, Starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, amorphous cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil Etc. can be mentioned. In addition, the pharmaceutical composition of the present invention may further include a filler, an anticoagulant, a lubricant, a humectant, a perfume, an emulsifier, a preservative, and the like.

본 발명의 약학적 조성물은 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. The pharmaceutical composition 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 at a reasonable benefit / risk ratio applicable to medical treatment, and an effective dose level means the type, severity, activity of the drug, Sensitivity to drug, time of administration, route of administration and rate of release, duration of treatment, factors including concurrent use of drugs, and other factors well known in the medical arts.

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 pharmaceutical compositions of the present invention may be administered as individual therapeutic agents or in combination with other therapeutic agents, may be administered sequentially or simultaneously with conventional therapeutic agents, and may be administered as single or multiple doses. Taking all of the above factors into consideration, it is important to administer an amount that can obtain the maximum effect in a minimum amount without side effects, which can be easily determined by those skilled in the art.

본 발명의 약학적 조성물에서 항혈전 활성을 갖는 성분의 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. The effective amount of the component having antithrombotic activity 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 per body weight, preferably 100 to 3,000 mg daily or every other day. It may be administered or divided into 1 to 3 times a day. However, the dosage may be increased or decreased depending on the route of administration, the severity of the disease, sex, weight, age, etc., and the above dosage does not 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(intra-cerebroventricular) 주사에 의해 투여될 수 있다. 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. The pharmaceutical composition of the present invention can be administered to a subject through various routes. All modes of administration can be expected, for example by oral, rectal or intravenous, intramuscular, subcutaneous, intrauterine dural or intra-cerebroventricular injections. As used herein, "administration" means providing a patient with any substance by any suitable method, wherein the route of administration of the pharmaceutical composition of the present invention is oral or parenteral via all common routes as long as the target tissue can be reached. Oral administration. 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. "Subject" in the present invention 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 mammals, and more preferably humans.

바람직한 구체예로서, 본 발명의 옥미수·호박 가미 경옥고는 혈전증의 예방 또는 개선용 건강 기능 식품의 용도로서 적용될 수 있다. As a preferred embodiment, the jade water, pumpkin kamikaze jadeite of the present invention can be applied as a use of a dietary supplement for the prevention or improvement of thrombosis.

본 발명의 항혈전 활성이 우수한 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. Examples of the food containing the active ingredient having excellent antithrombotic activity include various foods, beverages, gums, teas, vitamin complexes, health supplements, and the like, which are powders, granules, tablets, capsules, or beverages. Available in form.

본 발명의 활성 성분은 일반적으로 전체 식품 중량의 0.01 내지 15중량%로 가할 수 있으며, 건강음료 조성물은 100 ml를 기준으로 0.02 내지 10g, 바람직하게는 0.3 내지 1g의 비율로 가할 수 있다. The active ingredient of the present invention can generally be added at 0.01 to 15% by weight of the total food weight, the health beverage composition may be added in a ratio of 0.02 to 10g, preferably 0.3 to 1g based on 100 ml.

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. 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. 상기 향미제로는 타우마틴, 레바우디오시드 A, 글리시르히진, 사카린, 아스파르탐 등을 사용할 수 있다. 상기 향미제의 비율은 본 발명의 건강 기능 식품 100ml당 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. In addition to containing the compound as an essential ingredient in the indicated ratios, the health functional food of the present invention may contain food-acceptable food supplement additives such as natural carbohydrates and various flavoring agents as additional ingredients. Examples of the natural carbohydrates include conventional sugars such as monosaccharides such as glucose and fructose, disaccharides such as maltose and sucrose, and polysaccharides such as dextrin and cyclodextrin, and sugar alcohols such as xylitol, sorbitol, and erythritol. As the flavoring agent, tau martin, rebaudioside A, glycyrgin, saccharin, aspartame and the like can be used. The proportion of the flavoring agent is generally used from about 1 to 20 g, preferably from 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, synthetic flavors and natural flavoring agents, colorants and neutralizing agents, pectic acid and salts thereof, alginic acid and salts thereof, organic acids, protective colloids Thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohols, carbonation agents used in carbonated drinks and the like.

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 상기 활성 분획물 100 중량부 당 0.01 내지 약 20중량부의 범위에서 선택되는 것이 일반적이다.In addition, the health functional food of the present invention may contain a flesh for preparing natural fruit juice, fruit juice beverage, vegetable beverage and the like. These components can be used independently or in combination. The proportion of such additives is generally selected from the range of 0.01 to about 20 parts by weight per 100 parts by weight of the active fraction 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 with reference to Examples. The following examples are only preferred embodiments of the present invention, and the scope of the present invention is not limited to the following examples.

[[ 실시예Example ]]

실시예Example 1:  One: 옥미수Jade Water ·호박 가미 Pumpkin kamikaze 경옥고의Jadeite 조제와 이의 이화학적 특성 및 유용 성분 성분 분석  Preparation and Analysis of Physicochemical Properties and Useful Components

인삼 분말 3중량%, 백복령 분말 3중량%, 생지황 분말 12중량%, 옥미수 49중량%, 호박 21중량% 및 벌꿀 12%를 혼합하고, 이를 95℃에서 48시간 동안 가열 추출하고, 이를 여과한 후 26브릭스로 농축하여 제조한 옥미수·호박 가미 경옥고의 이화학적 특성, 유용성분 분석 및 관능성 평가 결과는 각각 표 1, 표 2 및 표 3에 나타내었다. 이때 대조군으로는 시판 경옥고를 이용하였다. 3% by weight of ginseng powder, 3% by weight of Baekbokryeong powder, 12% by weight of raw sulfur powder, 49% by weight of jade water, 21% by weight of pumpkin, and 12% of honey, which were heated and extracted at 95 ° C. for 48 hours and filtered. The results of physicochemical properties, useful component analysis and sensory evaluation of Okmisu-zucchini jadeite jadeite prepared by concentrating to 26 briquettes are shown in Table 1, Table 2 and Table 3, respectively. At this time, a commercial jadeite was used as a control.

Figure pat00001
Figure pat00001

그 결과, 표 1에 나타낸 바와 같이, 본 발명의 옥미수·호박 가미 경옥고는 시판 경옥고와 비해 1/6 정도의 산도를 나타내었으며, 낮은 명도와 황색도, 높은 적색도를 나타내었다. 그러나, 전체적인 색차는 시판 경옥고와 유사하였다. 이때, 색차 분석은 Hunter Color Difference meter(Super color SP-80 Colormeter, Tokyo Denshoku Co., Japan)를 이용하여 측정하였으며, 명도(백색 100 ~ 0 검정색), 적색도(적색 100 ~ -80 녹색), 황색도(황색 70 ~ -80 검정색)를 측정하였다. 이때, 표준백판의 색도는 L 값이 92.44, a 값이 -0.06, b 값이 1.35로 기준을 정하였으며, 시료당 3회 측정하여 평균값을 구하여 나타내었고 색차(△E)는 다음의 식을 이용하여 계산하였다.As a result, as shown in Table 1, the jade water-pumpkin kerbstone of the present invention showed an acidity of about 1/6 compared with commercial jadeite, and showed low brightness, yellowness, and high redness. However, the overall color difference was similar to that of commercial jadeite. At this time, the color difference analysis was measured using a Hunter Color Difference meter (Super color SP-80 Colormeter, Tokyo Denshoku Co., Japan), brightness (white 100 ~ 0 black), redness (red 100 ~ -80 green), Yellowness (yellow 70-80 black) was measured. At this time, the chromaticity of the standard whiteboard was set to L. 92.44, a value of -0.06, and b value of 1.35. The average value was obtained by measuring three times per sample, and the color difference (△ E) was expressed by the following equation. Calculated by

Figure pat00002
Figure pat00002

시판 경옥고 및 옥미수·호박 가미 경옥고의 총 폴리페놀, 총 플라보노이드, 총 당 및 환원당 함량을 측정하였다. 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, 총 당은 phenol-sulfuric acid법을 이용하여 정량하였다. The total polyphenols, total flavonoids, total sugars and reducing sugars contents of commercial jadeite and chalcedony amber amber jadeite were measured. The total polyphenol content was added to 400μl of the extracted sample solution, 50μl of Folin-ciocalteau, 100μl of Na 2 CO 3 saturated solution, and left at room temperature for 1 hour and absorbance at 725nm. Tannic acid was used as the standard reagent. For the total flavonoid content, each sample was extracted by stirring for 18 hours with methanol, 4 ml of 90% diethylene glycol was added to 400 µl of the filtered extract sample, 40 µl of 1N NaOH was added thereto, and the absorbance was measured at 420 nm after 1 hour of reaction at 37 ° C. Rutin was used as a standard reagent. Reducing sugar was determined by DNS method and total sugar was determined by phenol-sulfuric acid method.

Figure pat00003
Figure pat00003

그 결과, 표 2에 나타낸 바와 같이, 본 발명의 옥미수·호박 가미 경옥고는 시판 경옥고와 비해 총 폴리페놀 함량은 1.3배 높았으나, 총 플라보노이드 함량은 5.7배 높게 나타났다. 또한, 보다 낮은 환원당 함량을 나타내었다. As a result, as shown in Table 2, the total polyphenol content was 1.3 times higher than that of commercial jadeite, but the total flavonoid content was 5.7 times higher than that of commercial jadeite. It also showed a lower reducing sugar content.

한편, 본 발명의 옥미수·호박 가미 경옥고와 시판 경옥고의 관능성을 맛, 향, 목넘김 및 전체적 선호도로 평가한 결과, 시판 경옥고 대비 아주 우수한 관능성을 확인하였으며, 한약에 대해 거부감을 나타내는 청소년 및 20대 여성들도 부담감 없이 마실 수 있음을 확인하였다(표 3).On the other hand, as a result of evaluating the functionalities of the jade and zucchini jadeite and commercial jadeite in the present invention with taste, aroma, thirst, and overall preference, it was confirmed that the sensory ability was superior to that of commercial jadeite, Women in their twenties also could feel free to drink (Table 3).

Figure pat00004
Figure pat00004

실시예Example 2:  2: 옥미수Jade Water ·호박 가미 Pumpkin kamikaze 경옥고의Jadeite 혈액응고 저해활성 평가  Blood coagulation inhibitory activity evaluation

실시예 1에서 제조된 옥미수·호박 가미 경옥고의 혈액응고 저해활성(혈전생성 억제활성)을 평가하였으며, 기존에 보고된 방법(Sohn et al., 2004. Kor. J. Pharmacogn 35. 52-61; Kwon et al., 2004. J. Life Science, 14. 509-513; 류 등 2010. J. Life Science, 20. 922-928)과 동일하게, 트롬빈 타임, 프로트롬빈 타임, 에이피티 타임을 측정하여 평가하였다. 혈장은 시판 control plasma(MD Pacific Technology Co., Ltd, Huayuan Industrial Area, China)를 사용하였으며 트롬빈 타임, 프로트롬빈 타임과 에이피티티 측정법은 다음과 같은 과정으로 수행되었다.The anticoagulant inhibitory activity (thrombotic inhibitory activity) of the jade water, pumpkin amber jadeite jadeite prepared in Example 1 was evaluated, and the previously reported method (Sohn et al., 2004. Kor. J. Pharmacogn 35. 52-61 Kwon et al., 2004. J. Life Science, 14. 509-513; and R. et al. 2010. J. Life Science, 20. 922-928), measuring thrombin time, prothrombin time, and aptitime Evaluated. Plasma was used as a commercial control plasma (MD Pacific Technology Co., Ltd, Huayuan Industrial Area, China), and thrombin time, prothrombin time and activity measurements were performed as follows.

트롬빈 타임(Thrombin Time)Thrombin Time

37℃에서 0.5U 트롬빈(Sigma Co., USA) 50μl와 20 mM CaCl2 50μl, 다양한 농도의 시료 추출액 10μl를 Amelung coagulometer KC-1A(Japan)의 튜브에 혼합하여 2분간 반응시킨 후, 혈장 100μl를 첨가한 후 혈장이 응고될 때까지의 시간을 측정하였다. 대조로는 아스피린(Sigma Co., USA)을 사용하였으며, 용매 대조구로는 시료 대신 DMSO를 사용하였다. DMSO의 경우 30.5초의 응고시간을 나타내었다. 트롬빈 저해 효과는 3회 이상 반복한 실험의 평균치로 나타내었으며, 트롬빈 저해 활성은 시료 첨가시의 응고시간을 용매 대조구의 응고시간으로 나눈 값으로 나타내었다.50 μl of 0.5 U thrombin (Sigma Co., USA), 50 μl of 20 mM CaCl 2 , and 10 μl of various concentrations of the sample extract were mixed in a tube of Amelung coagulometer KC-1A (Japan) for 2 minutes, followed by 100 μl of plasma. After addition, the time until plasma coagulates was measured. Aspirin (Sigma Co., USA) was used as a control, and DMSO was used instead of the sample as a solvent control. DMSO showed a solidification time of 30.5 seconds. The thrombin inhibitory effect was expressed as the average value of the experiment repeated three or more times, and the thrombin inhibitory activity was expressed as the coagulation time when the sample was added divided by the coagulation time of the solvent control.

프로트롬빈 타임(Prothrombin Time prothrombinprothrombin time) time)

표준혈장(MD Pacific Co., China) 70μl와 다양한 농도의 시료액 10μl를 Amelung coagulometer KC-1A(Japan)의 튜브에 첨가하여 37℃에서 3분간 가온 후, 130μl의 PT reagent를 첨가하고 혈장이 응고될 때까지의 시간을 3회 반복한 실험의 평균치로 나타내었다. 대조로는 아스피린(Sigma Co., USA)을 사용하였으며, 용매 대조구로는 시료 대신 DMSO를 사용하였다. DMSO의 경우 16.7초의 응고시간을 나타내었다. 프로트롬빈 저해활성은 시료 첨가시의 응고시간을 용매 대조구의 응고시간으로 나눈 값으로 나타내었다.70 μl of standard plasma (MD Pacific Co., China) and 10 μl of various concentrations of sample solution were added to a tube of Amelung coagulometer KC-1A (Japan), warmed at 37 ° C. for 3 minutes, and then 130 μl of PT reagent was added and the plasma coagulated. The time until was expressed as the average value of the experiment repeated three times. Aspirin (Sigma Co., USA) was used as a control, and DMSO was used instead of the sample as a solvent control. DMSO showed a solidification time of 16.7 seconds. The prothrombin inhibitory activity was expressed as the coagulation time at the time of sample addition divided by the coagulation time at the solvent control.

aPTTaPTT (activated Partial (activated Partial ThromboplastinThromboplastin Time)  Time)

혈장 100μl와 다양한 농도의 시료 추출액 10μl를 Amelung coagulometer KC-1A(Japan)의 튜브에 첨가하여 37℃에서 3분간 가온한 후, 50μl의 aPTT reagent(Sigma, ALEXINTM)를 첨가하고 다시 37℃에서 3분간 배양하였다. 이후 50μl CaCl2(35mM)을 첨가한 후 혈장이 응고될 때까지의 시간을 측정하였다. 용매 대조구로는 시료 대신 DMSO를 사용하였으며, 이 경우 58.1초의 응고시간을 나타내었다. aPTT의 결과는 3회 반복한 실험의 평균치로 나타내었으며, 혈액응고인자 저해활성은 시료 첨가시의 aPTT를 용매 대조구의 aPTT로 나눈 값으로 나타내었다. 100 μl of plasma and 10 μl of various concentrations of the sample extract were added to a tube of Amelung coagulometer KC-1A (Japan), warmed at 37 ° C. for 3 minutes, and then 50 μl of aPTT reagent (Sigma, ALEXIN TM ) was added again to 3 ° C. at 37 ° C. Incubate for minutes. Since 50 μl CaCl 2 (35mM) was added to measure the time until the plasma coagulate. DMSO was used as a solvent control instead of the sample, in which case it showed a solidification time of 58.1 seconds. The results of aPTT were shown as the average value of the experiment repeated three times, and the blood coagulation factor inhibitory activity was expressed as aPTT at the time of sample addition divided by aPTT of the solvent control.

Figure pat00005
Figure pat00005

그 결과, 표 4에 나타난 바와 같이, 옥미수·호박 가미 경옥고는 동일 농도의 기존 경옥고에 비해 매우 강력한 트롬빈 저해 및 혈액응고인자 저해를 나타내어 혈전 생성을 효율적으로 저해하여 혈액순환 개선 효과를 기대할 수 있음을 확인하였다. 특히, 옥미수·호박 가미 경옥고는 뇌졸중 등의 질환에서 가장 문제되고 있는 내인성 혈전 생성(에이피티 타임으로 평가)을 효율적으로 억제할 수 있음을 확인하여, 기존의 경옥고가 가진 면역증강, 항피로 효과와 함께 강력한 항혈전 활성을 나타내어, 위장장애를 나타내는 아스피린을 대치할 수 있는 강력한 항혈전제로 개발 가능함을 제시하고 있다. As a result, as shown in Table 4, jade water and amber amber jadeite have very strong thrombin inhibition and coagulation factor inhibition compared to existing jadeite at the same concentration, which effectively inhibits blood clot production and can be expected to improve blood circulation. It was confirmed. In particular, Okmi-su and zucchini-grilled jadeite can effectively suppress endogenous thrombus formation (evaluated by epitaxial time), which is the most problematic in diseases such as stroke. In addition, it shows strong antithrombotic activity, suggesting that it can be developed as a powerful antithrombotic agent that can replace aspirin indicating gastrointestinal disorders.

실시예Example 3:  3: 옥미수Jade Water ·호박 가미 Pumpkin kamikaze 경옥고의Jadeite 인간 혈소판 응집저해활성 평가 Human platelet aggregation inhibitory activity evaluation

실시예 1에서 제조된 옥미수·호박 가미 경옥고의 인간 혈소판 응집저해활성을 평가하여 그 결과를 표 5 및 도 1에 나타내었다. 혈소판은 다양한 혈구세포와 함께 혈관을 순환하는 원반형의 작은 세포로서, 핵이 없는 대신 혈관손상보호 및 혈소판 응집과 관련된 다양한 물질을 고농도로 포함하는 cytoplasmic granule을 가지고 있으며, 혈관내벽의 손상이 나타나는 경우 응집인자들을 분비하고, 내피세포의 손상으로 노출된 collagen 등과 결합하여 1차 지혈 플러그(primary hemostatic plug)를 형성하여 혈전생성을 개시하는 중요한 세포이다. 따라서, 혈소판 응집저해는 혈전 생성을 방지하는 매우 중요한 활성이다. 혈소판 응집저해 활성은 다음의 방법에 준해 평가하였다. Human platelet aggregation inhibitory activity of the jade water, pumpkin amber jadeite jadeite prepared in Example 1 was evaluated, and the results are shown in Table 5 and FIG. 1. Platelets are discoid small cells that circulate blood vessels along with various blood cells. They have a cytoplasmic granule that contains high concentrations of various substances related to vascular damage protection and platelet aggregation instead of the nucleus. It is an important cell that secretes factors and binds collagen and the like exposed to damage of endothelial cells to form a primary hemostatic plug to initiate thrombus formation. Thus, platelet aggregation inhibition is a very important activity for preventing thrombus formation. Platelet aggregation inhibitory activity was evaluated according to the following method.

혈소판 응집저해 활성(Platelet aggregation inhibition activity)Platelet aggregation inhibition activity

혈소판은 인간 농축 혈소판을 사용하였으며, 이를 washing buffer(138mM NaCl, 2.7mM KCl, 12mM NaHCO3, 0.36mM NaH2PO4, 5.5mM Glucose, 1mM EDTA, pH 6.5)로 1회 세척하였다. 이후, suspending buffer(138mM NaCl, 2.7mM KCl, 12mM NaHCO3, 0.36mM NaH2PO4, 5.5mM Glucose, 0.49mM MgCl2, 0.25% gelatin, pH 7.4)에 재 현탁한 후, 3,000rpm에서 10분간 원심분리한 후 다시 suspending buffer에 재 현탁하였으며, 이때 혈소판 수는 4x109/ml이 되도록 조정하였다. 이후 1ml 현탁액에 2.5μl collagen을 가해 5분간 반응시키고, whole-blood aggregometer(Chrono-log, USA)를 사용하여 37℃에서 혈소판 응집을 측정하였다.Platelets were human concentrated platelets, which were washed once with washing buffer (138 mM NaCl, 2.7 mM KCl, 12 mM NaHCO 3 , 0.36 mM NaH 2 PO 4 , 5.5 mM Glucose, 1 mM EDTA, pH 6.5). After resuspending in suspending buffer (138mM NaCl, 2.7mM KCl, 12mM NaHCO 3 , 0.36mM NaH 2 PO 4 , 5.5mM Glucose, 0.49mM MgCl 2 , 0.25% gelatin, pH 7.4), and then resuspended at 3,000 rpm for 10 minutes. After centrifugation and resuspended in the suspending buffer, the platelet count was adjusted to 4x10 9 / ml. Then, 2.5 μl collagen was added to the 1 ml suspension for 5 minutes, and platelet aggregation was measured at 37 ° C. using a whole-blood aggregometer (Chrono-log, USA).

Figure pat00006
Figure pat00006

그 결과, 표 5에 나타낸 바와 같이, 용매대조구인 물을 첨가한 경우 인간 혈소판은 콜라겐 첨가에 의해 빠르고 강하게 응집이 나타났으며, 혈소판 응집저해제인 아스피린은 농도 의존적으로 혈소판 응집을 강력하게 저해하였다. 한편, 옥미수·호박 가미 경옥고는 6.5mg/ml 농도에서 기존 경옥고와 유사한 혈소판 응집도를 나타내어, 별도의 혈소판 응집문제는 야기하지 않는 것을 확인하였다. As a result, as shown in Table 5, when the solvent control water was added, human platelets were rapidly and strongly aggregated by the addition of collagen, and aspirin, a platelet aggregation inhibitor, strongly inhibited platelet aggregation in a concentration-dependent manner. On the other hand, Okmisu-pumpkin gyrite jadeite showed a platelet aggregation similar to that of existing jadeite at a concentration of 6.5mg / ml, it was confirmed that no platelet aggregation problem.

실시예Example 4:  4: 옥미수Jade Water ·호박 가미 Pumpkin kamikaze 경옥고의Jadeite 인간 적혈구 용혈 활성 평가 Human Erythrocyte Hemolytic Activity Assessment

옥미수와 호박은 오래전부터 식품 음료 및 한방재료로 사용하고 있으며, 별도의 부작용이 알려져 있지 않다. 따라서, 옥미수·호박 가미 경옥고는 별도의 특이 독성은 없을 것으로 판단된다. 옥미수·호박 가미 경옥고의 잠재적 급성 독성을 평가하기 위해 인간 적혈구 용혈 활성을 평가하였으며, 그 결과는 표 6에 나타내었다. 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.Okmisu and pumpkin have long been used as food beverages and herbal ingredients, no side effects are known. Therefore, jade water and pumpkin amber jadeite are unlikely to have any specific toxicity. Human erythrocyte hemolytic activity was assessed to assess the potential acute toxicity of jade water and pumpkin amber jadeite, and the results are shown in Table 6. The hemolytic activity was evaluated according to the previous report (Son Ho Yong, 2014, Korean J. Microbiol. Biotechnol. 42: 285 ~ 292), and 100 μl of human red blood cells washed three times with PBS was added to a 96-well microplate. 100 μl of various concentrations of the sample solution were added, followed by reaction at 37 ° C. for 30 minutes. After that, the reaction solution was centrifuged for 10 minutes (1,500 rpm) to transfer 100 μl of the supernatant to a new microtiter plate. Measured. DMSO (2%) was used as a solvent control of the sample, and Triton X-100 (1 mg / ml) was used as an experimental control for red blood cell hemolysis. Hemolytic activity was calculated using the following formula.

(( %% )) HemolysisHemolysis = [( = [( AbsAbs .S-.S- AbsAbs .C)/(.C) / ( AbsAbs .T-.T- AbsAbs .C)]×100.C)] × 100

Abs. S : 시료 첨가구의 흡광도,Abs. S: absorbance of the sample addition port,

Abs. C : DMSO 처가구의 흡광도,Abs. C: absorbance of DMSO house furniture,

AbsAbs . T : Triton X-100 . T: Triton X-100 첨가구의Addition of 흡광도. Absorbance.

Figure pat00007
Figure pat00007

먼저, 대조구로 사용된 DMSO와 증류수는 적혈구 용혈 활성이 없었으며, Triton X-100은 1mg/ml 농도에서 적혈구를 100% 용혈시킴을 확인하였다. 급성독성이 보고되어 있는, 항암제 엠포테라신 B는 0.0125 mg/ml 농도에서도 95% 이상의 적혈구 용혈활성을 나타내었다. 한편, 옥미수·호박 가미 경옥고는 기존 시판 경옥고와 마찬가지로 130mg/ml 농도에서도 용혈활성은 나타나지 않았다. First, DMSO and distilled water used as a control did not have erythrocyte hemolytic activity, Triton X-100 was confirmed that 100% hemolysis of red blood cells at a concentration of 1mg / ml. The anticancer drug emoterasin B, which has been reported to have acute toxicity, showed more than 95% erythrocyte hemolytic activity even at a concentration of 0.0125 mg / ml. On the other hand, hemolytic activity was not exhibited in jade water and pumpkin-grilled jadeite jade, even at 130 mg / ml concentration as in the existing commercial jadeite.

실시예Example 5:  5: 옥미수Jade Water ·호박 가미 Pumpkin kamikaze 경옥고의Jadeite 혈액응고 저해활성에 대한 혈장, 산 및 열 안정성 평가  Evaluation of Plasma, Acid and Thermal Stability for Inhibition of Coagulation

상기 실시예 1에서 얻은 옥미수·호박 가미 경옥고의 항응고 활성에 대한 혈장 안정성, 열 안정성 및 산 안정성을 확인하였다. 상기 옥미수·호박 가미 경옥고는 100℃에서 1시간 열 처리, pH 2(0.01M HCl)에서의 1시간 처리, 혈장에서 1시간 처리시에도 항응고 활성의 소실이 없이 우수한 활성을 유지하였다. 이상의 결과는 옥미수·호박 가미 경옥고는 기존 경옥고의 쓴맛, 신맛에 따른 낮은 관능성을 극복하고, 혈전생성을 강력히 억제하여 항혈전제로 실제적 이용이 가능함을 제시하고 있으며, 위장장애 등의 부작용이 보고된 아스피린을 보완, 대치할 수 있으리라 판단된다. Plasma stability, thermal stability, and acid stability of the anticoagulant activity of the jade water, zucchini, and amber jadeite obtained in Example 1 were confirmed. The jade water and zucchini kelp jadeite retained excellent activity without loss of anticoagulant 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. The above results suggest that Okmi-su and zucchini-grilled jadeite can overcome the low sensuality according to the bitter and sour taste of existing jadeite, and it can be effectively used as an antithrombicide by strongly inhibiting thrombogenesis, and side effects such as gastrointestinal disorders are reported. It is believed that the aspirin can be supplemented and replaced.

Claims (3)

인삼 100중량부에 대하여, 백복령 80~120중량부, 생지황 350~450중량부, 벌꿀 350~450중량부, 옥미수 1,500~1,800중량부 및 호박 600~800중량부를 혼합, 가열 추출, 여과 및 농축하여 제조되는 옥미수·호박 가미 경옥고를 유효성분으로 함유하는 혈전증의 예방 또는 치료용 약학적 조성물.100 to 100 parts by weight of ginseng, 80 to 120 parts by weight of Baekbokryeong, 350 to 450 parts by weight of raw turmeric, 350 to 450 parts by weight of honey, 1,500 to 1,800 parts by weight of jade water and 600 to 800 parts by weight of pumpkin, mixed, extracted, filtered and concentrated A pharmaceutical composition for the prevention or treatment of thrombosis, containing jade water, pumpkin amber jadeite jadeite, produced as an active ingredient. 인삼 100중량부에 대하여, 백복령 80~120중량부, 생지황 350~450중량부, 벌꿀 350~450중량부, 옥미수 1,500~1,800중량부 및 호박 600~800중량부를 혼합, 가열 추출, 여과 및 농축하여 제조되는 옥미수·호박 가미 경옥고를 유효성분으로 함유하는 혈액 응고 저해제.100 to 100 parts by weight of ginseng, 80 to 120 parts by weight of Baekbokryeong, 350 to 450 parts by weight of raw turmeric, 350 to 450 parts by weight of honey, 1,500 to 1,800 parts by weight of jade water and 600 to 800 parts by weight of pumpkin, mixed, extracted, filtered and concentrated A blood coagulation inhibitor comprising jade water, zucchini-flavored jadeite, produced as an active ingredient. 인삼 100중량부에 대하여, 백복령 80~120중량부, 생지황 350~450중량부, 벌꿀 350~450중량부, 옥미수 1,500~1,800중량부 및 호박 600~800중량부를 혼합, 가열 추출, 여과 및 농축하여 제조되는 옥미수·호박 가미 경옥고를 유효성분으로 함유하는 혈전증의 예방 또는 개선용 건강 기능 식품.100 to 100 parts by weight of ginseng, 80 to 120 parts by weight of Baekbokryeong, 350 to 450 parts by weight of raw turmeric, 350 to 450 parts by weight of honey, 1,500 to 1,800 parts by weight of jade water and 600 to 800 parts by weight of pumpkin, mixed, extracted, filtered and concentrated Health functional food for the prevention or improvement of thrombosis containing jade water, pumpkin kamikaze jadeite produced as an active ingredient.
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Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20030009560A (en) * 2003-01-06 2003-01-29 배진승 The galenical food and the maunfacuring process
KR100510239B1 (en) * 2005-07-26 2005-08-29 (주)엔돌핀에프앤비 Method for preparing a composition containing corn silk and dietary fibre
KR100989112B1 (en) * 2009-12-31 2010-10-26 권태선 Composition for medical treatment and gout prevention
KR101016195B1 (en) 2009-04-15 2011-02-22 남영제약영농조합법인 Restorative herb medicine containing Gastrodia elata and preparation methods thereof
KR101060309B1 (en) 2010-04-08 2011-08-29 충청대학 산학협력단 Restorative herb medicine with jujube and manufacturing method thereof
KR101198211B1 (en) 2010-03-12 2012-11-07 유한회사 해원 Manufacturing method of used the sea cucumbera restorative herb medicine
KR20140116301A (en) * 2013-03-22 2014-10-02 주식회사 풀무원 Composition that contains as active ingredient by the complex, pumpkin enhanced arginine effective in improving kidney function, strengthen and edema

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20030009560A (en) * 2003-01-06 2003-01-29 배진승 The galenical food and the maunfacuring process
KR100510239B1 (en) * 2005-07-26 2005-08-29 (주)엔돌핀에프앤비 Method for preparing a composition containing corn silk and dietary fibre
KR101016195B1 (en) 2009-04-15 2011-02-22 남영제약영농조합법인 Restorative herb medicine containing Gastrodia elata and preparation methods thereof
KR100989112B1 (en) * 2009-12-31 2010-10-26 권태선 Composition for medical treatment and gout prevention
KR101198211B1 (en) 2010-03-12 2012-11-07 유한회사 해원 Manufacturing method of used the sea cucumbera restorative herb medicine
KR101060309B1 (en) 2010-04-08 2011-08-29 충청대학 산학협력단 Restorative herb medicine with jujube and manufacturing method thereof
KR20140116301A (en) * 2013-03-22 2014-10-02 주식회사 풀무원 Composition that contains as active ingredient by the complex, pumpkin enhanced arginine effective in improving kidney function, strengthen and edema

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
Tae-Ho Kim 외. Journal of Ethnopharmacology. Vol. 178, 2016, pp. 172-179* *
황완균 외, 1994, 생약학회지 25: 51-58

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