KR102218529B1 - Composition comprising Salvia miltiorrhiza and red ginseng biotransformation extract for improving, preventing and treating of cardiovascular disease - Google Patents
Composition comprising Salvia miltiorrhiza and red ginseng biotransformation extract for improving, preventing and treating of cardiovascular disease Download PDFInfo
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- KR102218529B1 KR102218529B1 KR1020190086666A KR20190086666A KR102218529B1 KR 102218529 B1 KR102218529 B1 KR 102218529B1 KR 1020190086666 A KR1020190086666 A KR 1020190086666A KR 20190086666 A KR20190086666 A KR 20190086666A KR 102218529 B1 KR102218529 B1 KR 102218529B1
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- extract
- red ginseng
- ginseng
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- enzyme
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Abstract
본 발명은 단삼(Salvia miltiorrhiza) 생물전환 추출물 및 홍삼(red ginseng) 생물전환 추출물을 포함하는 심혈관계 질환 예방 또는 치료용 조성물에 관한 것으로서, 상기 단삼 추출물 및 홍삼 추출물에 효소처리 후 트리코데르마 레에세이(Trichoderma reesei) 배양액을 반응시켜 제조한 생물전환 복합추출물은 내피세포의 활성을 높이고 염증을 억제하는 효과가 있으므로, 이를 효과적으로 심혈관계 질환의 예방 또는 치료에 이용할 수 있다.The present invention relates to a composition for preventing or treating cardiovascular diseases comprising a Salvia miltiorrhiza biotransformation extract and a red ginseng biotransformation extract, wherein the trichoderma reessay after enzymatic treatment of the dansam extract and red ginseng extract (Trichoderma reesei) Since the biotransformation complex extract prepared by reacting the culture medium has the effect of increasing the activity of endothelial cells and inhibiting inflammation, it can be effectively used for the prevention or treatment of cardiovascular diseases.
Description
본 발명은 단삼(Salvia miltiorrhiza) 생물전환 추출물 및 홍삼(red ginseng) 생물전환 추출물을 포함하는 심혈관계 질환의 개선, 예방 또는 치료용 조성물에 관한 것으로서, 더욱 상세하게는 단삼 추출물 및 홍삼 추출물에 효소처리 후 트리코데르마 레에세이(Trichoderma reesei) 배양액을 반응시켜 제조한, 심혈관계 질환의 개선에 효과가 있는 생물전환 복합추출물에 관한 것이다.The present invention relates to a composition for the improvement, prevention or treatment of cardiovascular diseases comprising a Salvia miltiorrhiza bioconversion extract and a red ginseng biotransformation extract, and more particularly, an enzyme treatment on a dansam extract and a red ginseng extract It relates to a biotransformation complex extract that is effective in improving cardiovascular disease, prepared by reacting a culture medium of Trichoderma reesei.
심혈관계 질환은 현대사회에서 암과 더불어 2대 사망원인으로 꼽힌다. 만약 대한민국이 2017년에 개정된 미국 심장학회 권고치 기준에 따른다면, 국민의 절반인 약 2,600만명이 고혈압 환자가 된다고 한다.Cardiovascular disease is one of the two major causes of death along with cancer in modern society. If the Republic of Korea follows the standards of the American Heart Association revised in 2017, about 26 million people, or half of the people, will become hypertensive.
심장과 혈관과 관련된 질환에는 고혈압, 뇌경색, 뇌출혈, 동맥경화, 심근경색 등이 있으나 이들 질환의 원인은 매우 다양하고 복합적이다. 고혈압의 치료 목표는 고혈압에 의한 혈관, 뇌, 심장, 신장, 간장 등의 합병증을 막아 건강하게 생활할 수 있도록 하는 것으로, 치료제도 중요하지만 평소 기능을 건강하게 유지하고, 이미 기능이 떨어졌다면 속히 기능을 개선시키고, 더 나아가 예방을 할 수 있는 건강기능식품 조성물이 더욱 중요하며 시급한 실정이다.Diseases related to heart and blood vessels include high blood pressure, cerebral infarction, cerebral hemorrhage, arteriosclerosis, and myocardial infarction, but the causes of these diseases are very diverse and complex. The goal of treatment for hypertension is to prevent complications such as blood vessels, brain, heart, kidney, and liver caused by high blood pressure so that you can live a healthy life.The treatment is also important, but it is important to keep your usual function healthy, and if the function has already fallen, it will function quickly. The health functional food composition that can improve and further prevent it is more important and urgent.
미국 심장학회에서는 고혈압 기준을 130으로 낮추었고 이는 초기부터 더 적극적으로 혈압을 관리하는 것이 건강에 매우 중요하다는 것을 보여준 것이라고 알렸다.The American Heart Association lowered the high blood pressure standard to 130, which it said showed that managing blood pressure more actively from the beginning is very important to health.
그러나 일반적으로 고혈압 치료제는 한번 복용하면 평생 복용해야 하는 경우가 대부분이며, 많은 부작용들이 보고되고 있다. 따라서 이러한 질환은 사전에 예방하고 기능을 개선시키는 것이 매우 필요하다.However, in general, hypertension treatments are usually required to be taken for a lifetime once taken, and many side effects have been reported. Therefore, it is very necessary to prevent these diseases in advance and improve their function.
현재 사용되고 있는 주요 혈압강하 치료제들의 부작용은 다음과 같다. 이뇨제계 고혈압약은 저칼슘혈증, 고뇨산증, 고혈당, 고지혈증, 성기능장해, 고칼륨혈증 등을 유발하고, 교감신경차단계 혈압강하제는 성기능 장해, 갈증, 우울증, 기립성 저혈압, 서맥, 천식, 심부전 등이 나타난다. 혈관 확장계 혈압 강하약은, 빈맥, 협심증, 무력감, 다뇨, 홍조, 두통, 서맥 등이 나타난다. 안지오텐신 II 저해제는 급속한 신기능저하, 뇨독증, 심부전 등의 부작용이 나타나며, 5-HT 수용체 차단제는 두통, 입마름, 오심, 현기증, 발진, 소양감, 미각이상, 발열, 백혈구 감소, 신부전증, 관절통 등을 유발한다. 또한 고지혈증에 사용되는 스타틴계열 약물 역시, 근무력, 뇌기능저하, 코엔자임 q10 생성 저하, 간장애 등 부작용이 보고되고 있다. The side effects of major antihypertensive drugs currently in use are as follows. Diuretic hypertension drugs cause hypocalcemia, hyperuricemia, hyperglycemia, hyperlipidemia, sexual dysfunction, hyperkalemia, etc., and sympathetic hypertension-lowering drugs are sexual dysfunction, thirst, depression, orthostatic hypotension, bradycardia, asthma, heart failure. Light appears. Vasodilator blood pressure lowering drugs, tachycardia, angina, weakness, polyuria, flushing, headache, bradycardia and the like appear. Angiotensin II inhibitors have side effects such as rapid decline in renal function, uremia, and heart failure, and 5-HT receptor blockers cause headache, dry mouth, nausea, dizziness, rash, itching, taste disorders, fever, leukocyte reduction, kidney failure, joint pain, etc. do. In addition, statin drugs used for hyperlipidemia have also reported side effects such as myasthenia, decreased brain function, decreased coenzyme q10 production, and liver failure.
또한 현재 시중에 나와 있는 혈압조절 및 콜레스테롤 관련 기능식품들은 주로 코엔자임 q10, 정어리, 사탕수수인 폴리코사놀, 오메가 3 정도이나 모두 근본적인 개선에는 한계가 많다. 그 이유로는 오메가 3는 최근 연구발표에 의하면 효과가 유의하지 않다고 보고되었고, 코엔자임 q10은 항산화제이며, 폴리코사놀은 LDL콜레스테롤을 떨어뜨린다고 하나 콜레스테롤이 심혈관 건강에 해롭다는 보고는 오류가 많다는 사실이 지적되고 있으며, 오히려 콜레스테롤은 인체에 매우 필요한 중요한 물질로 알려지고 있다.In addition, blood pressure control and cholesterol-related functional foods currently on the market are mainly coenzyme q10, sardines, sugar cane policosanol, and omega 3, but all of them have limitations in fundamental improvement. For that reason, it is reported that omega 3 has no significant effect according to a recent research publication, coenzyme q10 is an antioxidant, and policosanol lowers LDL cholesterol, but it is pointed out that there are many errors in reporting that cholesterol is harmful to cardiovascular health. Rather, cholesterol is known as an important substance very necessary for the human body.
심혈관의 기능이 나빠지는 근본적인 이유는 내피세포의 손상으로부터 시작된다. 내피세포의 손상은 여러 이유에서 유발되나, 주요 원인으로는 산화에 의한 만성염증 및 그로 인한 손상, 고혈당으로 인한 혈액의 탁도 증가, 대식세포의 혈관세포점착, 세포노화 등을 꼽을 수 있다.The fundamental reason for the deterioration of cardiovascular function starts with damage to endothelial cells. Damage to endothelial cells is caused by various reasons, but the main causes include chronic inflammation and damage caused by oxidation, increased blood turbidity due to hyperglycemia, vascular cell adhesion of macrophages, and cell aging.
혈관의 95%는 모세혈관이며, 혈관세포의 손상 및 노화로 인해 혈관의 탄력성이 떨어지고, 혈전 및 프라그가 혈관에 쌓이게 되면 점차 혈류의 흐름이 지체되기 시작하며, 심장은 혈류의 흐름을 더욱 강하게 하기 위해 혈압을 높이게 된다. 혈관의 압력이 높아짐에 따라 혈관의 손상은 다시 가속화되는 악순환에 빠진다.95% of blood vessels are capillaries, and the elasticity of blood vessels decreases due to damage and aging of blood vessel cells, and when blood clots and plaques accumulate in the blood vessels, the blood flow gradually begins to retard, and the heart strengthens the blood flow. To increase blood pressure. As the pressure in the blood vessels increases, the damage to the blood vessels enters a vicious circle that accelerates again.
그러므로 혈관의 세포가 건강해지고, 혈액의 탁도 개선으로 혈행이 개선된다면 혈압이 자연스럽게 정상적으로 조절되고, 각종 심혈관 건강의 개선이 근본적으로 이루어질 수 있을 것이다.Therefore, if blood vessel cells become healthy and blood circulation is improved by improving blood turbidity, blood pressure is naturally regulated and various cardiovascular health improvements can be fundamentally achieved.
이러한 목적을 달성하기 위해 본 발명진은 식품공전에 등재된 식품 원료 중 전통적으로 심혈관 관련 기능 개선에 탁월한 약재인 인삼(홍삼)과 단삼을 선별하였다.To achieve this purpose, the present inventors selected ginseng (red ginseng) and sweet ginseng, which are traditionally excellent medicinal materials for improving cardiovascular function, among food ingredients registered in the Food Code.
홍삼은 이미 자체로 혈행 개선과 항산화 효과로 기능성을 인정받았으며, 단삼은 중국 전통 약재서적인 본초강목, 신농본초경에서 어혈제거(탁한피 제거) 및 혈압강하, 심혈관 기능에 가장 좋은 상약으로 인정받고 있다. 단삼의 주요 생리활성 물질인 살비논산 b는 혈전분해 및 항산화 효과가 크며, 혈관내피세포에 여러 염증 물질들이 달라붙는 것을 예방함으로써 혈관세포를 보호하는 것으로 알려져 있다.Red ginseng has already been recognized for its function of improving blood circulation and antioxidant effects, and Danseng is recognized as the best medicine for removing blood stagnation (removing turbid blood), lowering blood pressure, and cardiovascular function in traditional Chinese herbal medicines, herbal medicine, and new herbal medicine. . Salbinonic acid b, which is the main physiologically active substance of Dansam, has great thrombolytic and antioxidant effects, and is known to protect vascular cells by preventing various inflammatory substances from sticking to vascular endothelial cells.
홍삼(인삼)의 주요 생리활성 물질인 사포닌은 약리활성이 매우 우수하여 다른 식물에서 발견되는 사포닌과는 별도로 진세노사이드라고 부른다. 진세노사이드는 담마란(dammarane) 골격을 갖는 배당체에 일종의 화학구조상 R1, R2, R3 위치에 결합된 당의 종류 및 개수에 따라 디올계(Protopanaxadiol; PPD)와 트리올계(Protopanaxatriol; PPT)의 진세노사이드 등으로 분류된다. Saponin, the main physiologically active substance of red ginseng (ginseng), has excellent pharmacological activity, so it is called ginsenoside separately from saponins found in other plants. Ginsenosides are ginsenosides of diol-based (Protopanaxadiol; PPD) and triol-based (Protopanaxatriol; PPT) depending on the type and number of sugars bonded to the R1, R2, and R3 positions in a kind of glycoside having a dammarane skeleton. They are classified as side, etc.
그러나 진세노사이드가 체내에 흡수되기 위해서는 디올계 진세노사이드는 20-O-β-D-[0005] 글루코피라노실-20(S)-프로토파낙사디올(20-O-β-D-glucopyranosyl-20(S)-protopanaxa-diol, FGM 1, 이하, ‘화합물 K(Compound K)’라 함)로, 그리고 트리올계 진세노사이드는 20(S)-프로토파낙사트리올(20(S)-protopanaxatriol, FGM 4)로 분해된 후 체내에 흡수되면서 효능을 발휘하는데 열이나 산, 압력, 소화효소 등에 의해서는 소량만 흡수될 뿐이다. 최근 연구결과에 따르면 인삼 사포닌이 이러한 최종산물로 전환할 때 장내미생물이 필요하다고 밝혀졌다.However, for ginsenosides to be absorbed into the body, the diol-based ginsenosides are 20-O-β-D-[0005] glucopyranosyl-20(S)-protopanaxadiol (20-O-β-D-glucopyranosyl). -20(S)-protopanaxa-diol, FGM 1, hereinafter referred to as'Compound K'), and triol-based ginsenosides are 20(S)-protopanaxa-diol (20(S)) After being decomposed into -protopanaxatriol, FGM 4), it is absorbed into the body to exert its efficacy, but only a small amount is absorbed by heat, acid, pressure, digestive enzymes, etc. Recent research has shown that ginseng saponins require intestinal microbes to convert into these end products.
경구 복용한 사포닌이 컴파운드 K로 전환되어 흡수되려면 장내 미생물에 의해 분해되어야 하는데 일반인들 중 인분을 조사해 추정한 연구에서 정상인 중 30%는 사포닌을 대사할 수 있는 균이 전혀 없고, 비록 균이 있는 나머지 70% 중에도 대사 능력에 차이가 있어 디올계와 트리올계 사포닌을 모두 정상적으로 대사 할 수 있는 사람은 소수에 지나지 않았다.In order for saponin taken orally to be converted to compound K and be absorbed, it must be decomposed by intestinal microbes. In a study estimated by investigating human content among the general population, 30% of normal people do not have any bacteria that can metabolize saponin, although the remaining bacteria are present. Among 70%, there are differences in metabolic ability, so only a few people can metabolize both diol-based and triol-based saponins normally.
경희대 약학대학의 연구발표에 따르면, 건강한 성인 남자 24명을 대상으로 한 경구섭취실험에서 진세노사이드 1 mg 당 0.2 ng/mL의 컴파운드 K 최대 혈중 농도를 보이고, 경구섭취 컴파운드 K 1 mg당 15 ng/mL의 최대 혈중 농도를 보여 약 75배의 컴파운드 K 혈중 농도 차이를 나타내고 있다. 이로부터 일반 진세노사이드의 컴파운드 K 전환율이 장 속에서 매우 낮음을 알 수 있다. 또한 Rb1 등 주요 진세노사이드 자체의 체내 흡수율은 1% 미만으로 알려져 있다.According to a study published by Kyunghee University College of Pharmacy, a maximum blood concentration of Compound K of 0.2 ng/mL per 1 mg of ginsenoside was shown in an oral intake experiment of 24 healthy male adults, and 15 ng per mg of oral Compound K. The maximum blood concentration of /mL was shown, indicating a difference of about 75 times the compound K blood concentration. From this, it can be seen that the compound K conversion rate of general ginsenoside is very low in the intestine. In addition, it is known that the absorption rate of major ginsenosides such as Rb1 in the body is less than 1%.
이런 면에서 이미 외부에서 장내 미생물로 발효를 완료하여, 개인의 대사 기능에 관계없이 인삼의 유효성분을 흡수할 수 있는 형태로 전환시킴으로써, 누구나 효과를 볼 수 있는 컴파운드 K 강화 인삼 또는 홍삼 농축액을 개발하는 것은 매우 바람직하다고 볼 수 있다.In this regard, by already completing fermentation with intestinal microbes from the outside and converting it into a form that can absorb the active ingredients of ginseng regardless of the individual's metabolic function, we developed a compound K-fortified ginseng or red ginseng concentrate that anyone can benefit from. It can be considered very desirable to do.
인삼의 사포닌 성분 중 상기 진세노사이드 컴파운드 K의 수율을 개선하기 위한 선행기술로서 한국등록특허 제10-1409761호(2014.06.13)에서는 3종의 효소를 혼합 사용하여 컴파운드 K로 전환시키는 방법을 개시한 바 있으나, 전환과정 중 Rd와 F2에서 전환이 정지되어 컴파운드 K의 전환율이 너무 낮았다. 한국공개특허 제10-2016-0076851호(2016.07.01)에서는 1종의 효소와 사이톨레이즈(Cytolase) PCL5를 혼합하여 컴파운드 K로 전환시키는 방법을 게시한 바 있으나 상기와 같은 전환과정에 관련한 이유로 컴파운드 K의 전환율이 낮았다.As a prior art for improving the yield of the ginsenoside compound K among the saponin components of ginseng, Korean Patent Registration No. 10-1409761 (2014.06.13) discloses a method of converting to compound K by mixing three kinds of enzymes. However, the conversion rate of Compound K was too low because the conversion was stopped at Rd and F2 during the conversion process. Korean Patent Laid-Open Publication No. 10-2016-0076851 (2016.07.01) discloses a method of converting to compound K by mixing one enzyme and cytolase PCL5, but for reasons related to the above conversion process. The conversion rate of compound K was low.
단삼은 꿀풀과(Lamiaceae) 단삼속(genus Salvia)에 속하는 식물이며, 현재까지 110여 개 이상의 성분이 분리되어 각종 약리활성에 관한 연구가 진행 중이다. 단삼의 주요 성분 중 살비논산 B(salvianolic acid B)는 혈압 강하, 알츠하이머 예방, 항산화 효과, 간세포 보호, 항암효과, 만성염증완화 등 다양한 약리활성을 지닌 물질로 평가되었다. 독일 아벤티스(aventis)사의 연구에 따르면 살비논산 B를 포함한 단삼이 고혈압 약제보다 우수한 효과를 나타냈다고 보고한 바도 있다. 또한 싱가폴 국립대학 가정의학과에서는 단삼의 간암 억제효과 및 간암세포 세포사멸(Apoptosis) 유도를 실험적으로 증명하였으며, 그 외 다수의 연구진들의 연구들에 의하면 살비논산 A(salvianolic acid A)의 유방암 억제효과, 탄쉬논의 항암효과를 갖는다.Dansam is a plant belonging to the genus Salvia of the Lamiaceae family, and more than 110 components have been isolated so far, and studies on various pharmacological activities are ongoing. Salvianolic acid B, among the main ingredients of Dansam, has been evaluated as a substance with various pharmacological activities such as lowering blood pressure, preventing Alzheimer's, antioxidant effect, hepatocyte protection, anticancer effect, and alleviating chronic inflammation. According to a study by German Aventis (Aventis), it has also been reported that Salbinonic Acid B-containing Danseng has a superior effect than hypertension drugs. In addition, the Department of Family Medicine at the National University of Singapore has experimentally proved the inhibitory effect of single ginseng on liver cancer and induction of hepatocellular apoptosis (Apoptosis). According to studies by many other researchers, the inhibitory effect of salvianolic acid A on breast cancer, It has anticancer effect of tanshinone.
기존의 살비논산 B는 열수 추출, 혹은 에탄올 추출로 얻었으나, 본 발명에서는 발효공정을 추가하여 살비논산 B의 수율 증가를 획득하였고, 또한 살비논산 B의 활성도 역시 증가하는 결과를 획득하였다.Existing salbinonic acid B was obtained by hot water extraction or ethanol extraction, but in the present invention, a fermentation process was added to obtain an increase in the yield of salbinonic acid B, and the activity of salbinonic acid B was also increased.
단삼의 생물전환기술을 이용한 가공형태는 선행된 전례가 없으며, 특히 홍삼과 혼합하여 복합 생물전환 반응을 수행한 공정은 새로운 제조방법이다. 또한 특정 비율의 홍삼과 단삼의 복합 반응은 홍삼 반응시 생성되는 컴파운드 K의 용해도를 개선시켜 체내 흡수율 증가가 기대되고 있다.There is no precedent for the processing type using the bioconversion technology of Danseng. In particular, the process of performing a complex bioconversion reaction by mixing with red ginseng is a new manufacturing method. In addition, the complex reaction of red ginseng and sweet ginseng in a specific ratio improves the solubility of compound K generated during the red ginseng reaction and is expected to increase the absorption rate in the body.
기존 선행 특허 10-0341368은 단삼과 삼칠을 물과 에탄올로 추출하고 그 추출물에 용뇌를 섞어 만든 심혈관 질환 치료제가 있으며, 또한 다른 특허 10-0327894 (2013년에 소멸) 역시 단삼과 삼칠의 혼합 추출물을 포함하는 고혈압 치료 및 콜레스테롤 저하 조성물이 있으나 단순히 물과 에탄올로 추출한 조성물이다. Existing patent 10-0341368 is a cardiovascular disease treatment made by extracting Dansam and Samchil with water and ethanol and mixing the extract with Dragonbrain, and another patent 10-0327894 (disappeared in 2013) also uses a mixed extract of Dansam and Samchil. There is a composition for treating hypertension and lowering cholesterol, but it is simply a composition extracted with water and ethanol.
더욱이 단삼 및 삼칠근 추출물의 심혈관 관련 기능 개선 작용과 관련하여서는 이미 위 선행특허 출원일 이전에 반포된 간행물인 Am. J. Chin. Med., vol. 14. pp. 145-152 (1986)에 삼칠근과 단삼의 추출물이 알비노 렛트와 토끼에서 혈압저하작용과 이들 추출물이 심혈관 시스템에 유효한 효과가 있음이 게재되었고, Zhongguo Zhong Xi Yi, Jie He Za Zhi, vol. 17. no. 5, pp. 292-294 (1997. 5)에는 단삼, 삼칠근을 포함하는 조성물이 혈압 강하작용이 공지된 바 있다.Moreover, regarding the improvement of cardiovascular-related functions of extracts of Dansam and Samchil-geun, Am. J. Chin. Med., vol. 14. pp. 145-152 (1986) reported that the extracts of Samchil-geun and Danseng were effective in reducing blood pressure in albino rats and rabbits and that these extracts had an effective effect on the cardiovascular system, Zhongguo Zhong Xi Yi, Jie He Za Zhi, vol. 17. no. 5, pp. In 292-294 (1997. 5), a composition containing Dansam and Samchil muscle has been known to lower blood pressure.
또한 칭화대 연구발표에 따르면 인삼과 단삼의 혼합 추출물이 각각의 단일 추출물에 비해 동맥경화 개선에 시너지가 있었다. 그러나 고혈압에 대한 정보는 전혀 나타나 있지 않았다.In addition, according to the research publication of Tsinghua University, the mixed extract of ginseng and sweet ginseng had synergies in improving arteriosclerosis compared to each single extract. However, there was no information on hypertension.
이에 본 발명자들은 단삼(Salvia miltiorrhiza) 및 홍삼(red ginseng) 추출물에 효소처리 후 미생물 배양액을 반응시켜 제조한 생물전환 복합추출물에서 컴파운드 K 및 살비논산 B의 함량이 높게 나타나고, 내피세포의 활성 촉진 및 염증 억제 효과 또한 월등히 우수한 것을 확인하였다. Accordingly, the present inventors found that the contents of compound K and salbinonic acid B are high in the biotransformation complex extract prepared by reacting a microbial culture solution after enzyme treatment with extracts of Salvia miltiorrhiza and red ginseng, and promoting endothelial cell activity and It was confirmed that the inhibitory effect on inflammation was also remarkably excellent.
이에, 본 발명의 목적은 단삼 생물전환 추출물 및 홍삼 생물전환 추출물을 포함하는 심혈관계 질환 예방 또는 치료용 약학 조성물을 제공하는 것이다.Accordingly, an object of the present invention is to provide a pharmaceutical composition for preventing or treating cardiovascular diseases comprising a biotransformation extract of dansam and red ginseng biotransformation extract.
본 발명의 다른 목적은 다음 단계를 포함하는, 단삼 생물전환 추출물 및 홍삼 생물전환 추출물을 포함하는 심혈관계 질환 예방 또는 치료용 약학 조성물의 제조방법을 제공하는 것이다:Another object of the present invention is to provide a method for preparing a pharmaceutical composition for the prevention or treatment of cardiovascular diseases comprising the following steps:
단삼 추출물 및 홍삼 추출물에 양조 효소를 첨가하여 단삼 효소반응물 및 홍삼 효소반응물을 제조하는 효소처리 단계; 및Enzymatic treatment step of preparing a sweet ginseng enzyme reaction product and a red ginseng enzyme reaction product by adding a brewing enzyme to the sweet ginseng extract and the red ginseng extract; And
상기 단삼 효소반응물 및 홍삼 효소반응물에 미생물 배양액을 반응시켜 단삼 생물전환 추출물 및 홍삼 생물전환 추출물을 제조하는 생물전환 단계.A bioconversion step of reacting a microbial culture solution with the enzyme reaction product of Dansam and the enzyme reaction of red ginseng to prepare a bioconversion extract and a bioconversion extract of red ginseng.
본 발명의 또 다른 목적은 단삼 생물전환 추출물 및 홍삼 생물전환 추출물을 포함하는 심혈관계 질환 개선용 식품 조성물을 제공하는 것이다. Another object of the present invention is to provide a food composition for improving cardiovascular disease comprising a biotransformation extract of dansam and red ginseng biotransformation extract.
본 발명의 또 다른 목적은 다음 단계를 포함하는, 단삼 생물전환 추출물 및 홍삼 생물전환 추출물을 포함하는 심혈관계 질환 개선용 식품 조성물의 제조방법을 제공하는 것이다:Another object of the present invention is to provide a method for preparing a food composition for improving cardiovascular diseases comprising the biotransformation extract and red ginseng biotransformation extract comprising the following steps:
단삼 추출물 및 홍삼 추출물에 양조 효소를 첨가하여 단삼 효소반응물 및 홍삼 효소반응물을 제조하는 효소처리 단계; 및Enzymatic treatment step of preparing a sweet ginseng enzyme reaction product and a red ginseng enzyme reaction product by adding a brewing enzyme to the sweet ginseng extract and the red ginseng extract; And
상기 단삼 효소반응물 및 홍삼 효소반응물에 미생물 배양액을 반응시켜 단삼 생물전환 추출물 및 홍삼 생물전환 추출물을 제조하는 생물전환 단계.A bioconversion step of reacting a microbial culture solution with the enzyme reaction product of Dansam and the enzyme reaction of red ginseng to prepare a bioconversion extract and a bioconversion extract of red ginseng.
본 발명의 또 다른 목적은 단삼 생물전환 추출물 및 홍삼 생물전환 추출물의 심혈관계 질환 예방 또는 치료 용도에 관한 것이다.Another object of the present invention relates to the use of the biotransformation extract and red ginseng biotransformation extract to prevent or treat cardiovascular diseases.
본 발명은 단삼(Salvia miltiorrhiza) 생물전환 추출물 및 홍삼(red ginseng) 생물전환 추출물을 포함하는 심혈관계 질환 예방 또는 치료용 조성물에 관한 것으로, 본 발명자들은 본 발명에 따른 조성물에서 컴파운드 K 및 살비논산 B의 함량이 높게 나타나고, 내피세포의 활성 촉진 및 염증 억제 효과 또한 월등히 우수함을 확인하였다.The present invention relates to a composition for preventing or treating cardiovascular diseases comprising a Salvia miltiorrhiza biotransformation extract and a red ginseng biotransformation extract, the inventors of the present invention in the composition according to the present invention, compound K and salbinonic acid B It was confirmed that the content of was high, and the effect of promoting the activation of endothelial cells and inhibiting inflammation was also excellent.
이하 본 발명을 더욱 자세히 설명하고자 한다.Hereinafter, the present invention will be described in more detail.
본 발명의 일 양태는 단삼 생물전환 추출물 및 홍삼 생물전환 추출물을 포함하는 심혈관계 질환 예방 또는 치료용 약학 조성물이다.One aspect of the present invention is a pharmaceutical composition for preventing or treating cardiovascular diseases comprising a biotransformation extract of dansam and red ginseng biotransformation extract.
단삼 생물전환 추출물 및 홍삼 생물전환 추출물은 각각 생물전환 공정을 실시하여 추출물을 제조한 후 혼합할 수 있고, 단삼 및 홍삼 추출물을 생물전환 공정을 실시하여 제조한 것을 이용할 수도 있다.The bioconversion extract and red ginseng bioconversion extract may be mixed after preparing the extract by performing a bioconversion process, respectively, and those prepared by performing the bioconversion process of the extracts of sweet ginseng and red ginseng may be used.
본 명세서상의 용어 "생물전환(biotransformation 또는 bioconversion)"이란, 생물의 생리적 기능을 이용해 첨가된 물질을 화학적으로 변형된 형태로 전환시키는 과정을 의미하고, 구체적으로, 생체의 기능 또는 생체가 가지고 있는 생촉매의 기능을 이용하여 새로운 신생물 제품을 생산하거나, 기존 화학합성공정에 의해 합성 및 생산되고 있는 기존 화학제품을 신생물 제품으로 대체하고자 하는 기술을 의미한다.The term "biotransformation or bioconversion" as used herein refers to a process of converting an added substance into a chemically modified form by using the physiological function of an organism, and specifically, a function of a living body or a living body possessed by a living body. It refers to a technology that uses the function of a catalyst to produce new neoplastic products or to replace existing chemical products synthesized and produced by the existing chemical synthesis process with neoplastic products.
상기 심혈관계 질환은 고혈압, 혈액순환장애 및 동맥경화로 이루어진 군으로부터 선택되는 것일 수 있으나, 이에 한정되는 것은 아니다.The cardiovascular disease may be selected from the group consisting of high blood pressure, blood circulation disorder, and arteriosclerosis, but is not limited thereto.
상기 조성물은 단삼 및 홍삼 복합효소반응물에 미생물 배양액을 첨가하여 제조된 것일 수 있고, 상기 미생물 배양액은 트리코데르마 레에세이(Trichoderma reesei), 아스퍼질러스 오리제(Aspergillus oryzae), 비피도박테리움 롱검(Bifidobacterium longum) 또는 락토바실러스 람노서스(Lactobacillus rhamnosus)로 이루어진 군으로부터 선택되는 1종 이상의 균주의 배양액인 것일 수 있으며, 예를 들어, 트리코데르마 레에세이 균주의 배양액인 것일 수 있으나, 이에 한정되는 것은 아니다.The composition may be prepared by adding a microbial culture solution to a complex enzyme reaction of sweet ginseng and red ginseng, and the microbial culture solution is Trichoderma reesei , Aspergillus oryzae , Bifidobacterium long gum ( Bifidobacterium longum ) or Lactobacillus rhamnosus ( Lactobacillus rhamnosus ) It may be a culture medium of one or more strains selected from the group consisting of, for example, it may be a culture medium of the Trichoderma reessay strain, but is limited thereto. It is not.
본 명세서상의 용어 "효소반응물"은 본 발명에서 제시하는 효소처리 공정을 수행한 결과물을 의미한다.The term "enzyme reactant" in the present specification refers to a result of performing the enzyme treatment process presented in the present invention.
상기 단삼 및 홍삼 복합효소반응물은 단삼 추출물 및 홍삼 추출물에 양조 효소를 첨가하여 제조되는 것일 수 있고, 펙티네이즈(Pectinase) 및 아라비네이즈(Arabinase)로 이루어진 군으로부터 선택되는 1종 이상의 효소, 또는 이를 발현하는 균주를 단삼 추출물 및 홍삼 추출물에 첨가하여 제조되는 것일 수 있으며, 예를 들어, 펙티네이즈 및 아라비네이즈, 또는 이를 동시 발현하는 균주를 단삼 추출물 및 홍삼 추출물에 첨가하여 제조되는 것일 수 있으나, 이에 한정되는 것은 아니다.The single ginseng and red ginseng complex enzyme reactant may be prepared by adding a brewing enzyme to the ginseng extract and red ginseng extract, and at least one enzyme selected from the group consisting of pectinase and arabinase, or expressing the same It may be prepared by adding the strain to the sweet ginseng extract and the red ginseng extract, for example, pectinase and arabinase, or may be prepared by adding a strain expressing the same to the sweet ginseng extract and the red ginseng extract, but limited thereto. It does not become.
본 명세서 상의 용어 "양조 효소"는 발효 공정에 의해 생산되는 주류의 생산 공정 상에 사용되는 효소를 의미하며, 보다 더 구체적으로는 저온 발효 공정 상에 사용될 수 있는 발효 효소들을 의미한다. 시판되는 양조 효소로서 Gluc Gin, Ginjou-koji, tome-koji 등을 구체적인 예로 들 수 있다.The term "brewing enzyme" as used herein refers to an enzyme used in the production process of alcoholic beverages produced by a fermentation process, and more specifically means fermentation enzymes that can be used in a low temperature fermentation process. Specific examples of commercially available brewing enzymes include Gluc Gin, Ginjou-koji, and tome-koji.
본 발명의 양조 효소는 앞선 실시 단계들을 통해 얻어진 결과물 100 중량부를 기준으로 1 내지 10 중량부, 더 구체적으로는 2 내지 8 중량부, 보다 더 구체적으로는 3 내지 7 중량부, 보다 더 구체적으로는 4 내지 6 중량부를 추가하여 상온보다 비교적 높은 온도에서 반응시킬 수 있다. 구체적으로 예를 들면, 25℃ 내지 55℃, 30℃ 내지 55℃, 35℃ 내지 55℃, 40℃ 내지 55℃, 45℃ 내지 55, 또는 48℃ 내지 52℃의 온도에서 반응시킬 수 있다. 반응 시간은 30분 내지 수시간 정도가 적당하며, 구체적으로 예를 들면, 30분 내지 6시간, 더 구체적으로 1시간 내지 5시간, 보다 더 구체적으로 2시간 내지 4시간 동안 반응시킬 수 있다.The brewing enzyme of the present invention is 1 to 10 parts by weight, more specifically 2 to 8 parts by weight, more specifically 3 to 7 parts by weight, and even more specifically, based on 100 parts by weight of the result obtained through the previous implementation steps. By adding 4 to 6 parts by weight, it can be reacted at a temperature relatively higher than room temperature. Specifically, for example, it may be reacted at a temperature of 25°C to 55°C, 30°C to 55°C, 35°C to 55°C, 40°C to 55°C, 45°C to 55°C, or 48°C to 52°C. The reaction time is suitably about 30 minutes to several hours, specifically, for example, 30 minutes to 6 hours, more specifically 1 hour to 5 hours, and even more specifically 2 hours to 4 hours.
본 발명의 일 구현예에서, 상기 단삼 및 홍삼 복합효소반응물은 단삼 추출물 및 홍삼 추출물에 펙티네이즈 및 아라비네이즈, 또는 아스페르길루스 니제르(Aspergillus niger var) 균주를 첨가하여 제조될 수 있다.In one embodiment of the present invention, the sweet ginseng and red ginseng complex enzyme reactant may be prepared by adding pectinase and arabinase, or Aspergillus niger var strain to the sweet ginseng extract and red ginseng extract.
상기 단삼 및 홍삼 복합효소반응물은 단삼 추출물 및 홍삼 추출물의 중량비를 1:9 내지 9:1, 1:9 내지 7:3, 1:9 내지 6:4, 1:9 내지 5:5, 3:7 내지 9:1, 3:7 내지 7:3 또는 3:7 내지 6:4로 포함하는 것일 수 있고, 예를 들어, 3:7 내지 5:5로 포함하는 것일 수 있으나, 이에 한정되는 것은 아니다.The single ginseng and red ginseng complex enzyme reactants are 1:9 to 9:1, 1:9 to 7:3, 1:9 to 6:4, 1:9 to 5:5, 3: It may be included in 7 to 9:1, 3:7 to 7:3 or 3:7 to 6:4, for example, it may be included in 3:7 to 5:5, but is limited thereto no.
상기 단삼 및 홍삼 복합효소반응물은 단삼 추출물 및 홍삼 추출물에 각각 효소처리 공정을 실시하여 수득한 효소반응물을 혼합하여 제조할 수 있고, 단삼 추출물 및 홍삼 추출물을 혼합한 복합추출물에 효소처리 공정을 실시하여 제조할 수도 있다.The sweet ginseng and red ginseng complex enzyme reactants can be prepared by mixing the enzyme reactants obtained by performing an enzyme treatment process on the sweet ginseng extract and the red ginseng extract, respectively, and by performing an enzyme treatment process on the complex extract obtained by mixing the sweet ginseng extract and the red ginseng extract. It can also be manufactured.
상기 단삼 추출물은 30 내지 80%(w/w), 30 내지 75%(w/w), 30 내지 70%(w/w), 30 내지 65%(w/w), 30 내지 60%(w/w), 30 내지 55%(w/w), 40 내지 80%(w/w), 40 내지 75%(w/w), 40 내지 70%(w/w), 40 내지 65%(w/w) 또는 40 내지 60%(w/w)의 에탄올을 용매로 하여 수득되는 것일 수 있고, 예를 들어, 40 내지 55%(w/w)의 에탄올을 용매로 하여 수득되는 것일 수 있으나, 이에 한정되는 것은 아니다.The Dansam extract is 30 to 80% (w/w), 30 to 75% (w/w), 30 to 70% (w/w), 30 to 65% (w/w), 30 to 60% (w /w), 30 to 55% (w/w), 40 to 80% (w/w), 40 to 75% (w/w), 40 to 70% (w/w), 40 to 65% (w /w) or 40 to 60% (w / w) of ethanol may be obtained as a solvent, for example, 40 to 55% (w / w) of ethanol may be obtained as a solvent, It is not limited thereto.
상기 홍삼 추출물은 30 내지 80%(w/w), 30 내지 75%(w/w), 30 내지 70%(w/w), 30 내지 65%(w/w), 30 내지 60%(w/w), 30 내지 55%(w/w), 40 내지 80%(w/w), 40 내지 75%(w/w), 40 내지 70%(w/w), 40 내지 65%(w/w) 또는 40 내지 60%(w/w)의 에탄올을 용매로 하여 수득되는 것일 수 있고, 예를 들어, 40 내지 55%(w/w)의 에탄올을 용매로 하여 수득되는 것일 수 있으나, 이에 한정되는 것은 아니다.The red ginseng extract is 30 to 80% (w / w), 30 to 75% (w / w), 30 to 70% (w / w), 30 to 65% (w / w), 30 to 60% (w /w), 30 to 55% (w/w), 40 to 80% (w/w), 40 to 75% (w/w), 40 to 70% (w/w), 40 to 65% (w /w) or 40 to 60% (w / w) of ethanol may be obtained as a solvent, for example, 40 to 55% (w / w) of ethanol may be obtained as a solvent, It is not limited thereto.
상기 조성물은 살비논산 B(salvianolic acid B) 및 컴파운드(compound) K을 포함하는 것일 수 있다.The composition may include salvianolic acid B and compound K.
본 발명의 다른 양태는 다음 단계를 포함하는, 단삼 생물전환 추출물 및 홍삼 생물전환 추출물을 포함하는 심혈관계 질환 예방 또는 치료용 약학 조성물의 제조방법이다:Another aspect of the present invention is a method of preparing a pharmaceutical composition for preventing or treating cardiovascular diseases comprising the biotransformation extract and red ginseng biotransformation extract comprising the following steps:
단삼 추출물 및 홍삼 추출물에 양조 효소를 첨가하여 단삼 효소반응물 및 홍삼 효소반응물을 제조하는 효소처리 단계; 및Enzymatic treatment step of preparing a sweet ginseng enzyme reaction product and a red ginseng enzyme reaction product by adding a brewing enzyme to the sweet ginseng extract and the red ginseng extract; And
상기 단삼 효소반응물 및 홍삼 효소반응물에 미생물 배양액을 반응시켜 단삼 생물전환 추출물 및 홍삼 생물전환 추출물을 제조하는 생물전환 단계.A bioconversion step of reacting a microbial culture solution with the enzyme reaction product of Dansam and the enzyme reaction of red ginseng to prepare a bioconversion extract and a bioconversion extract of red ginseng.
상기 방법은 효소처리 단계 이후에 양조 효소를 불활성화 시키는 불활성화 단계를 추가적으로 포함할 수 있다. 상술한 바와 같은 불활성화 단계의 실시에 의해 컴파운드 K가 프로토파낙사디올(protopanaxadiol; PPD)로 전환되는 것을 방지할 수 있다.The method may further include an inactivation step of inactivating the brewing enzyme after the enzyme treatment step. Compound K can be prevented from being converted to protopanaxadiol (PPD) by performing the inactivation step as described above.
상기 양조 효소는 펙티네이즈 및 아라비네이즈로 이루어진 군으로부터 선택되는 1종 이상의 효소일 수 있고, 양조 효소 대신 펙티네이즈 및 아라비네이즈로 이루어진 군으로부터 선택되는 1종 이상의 효소를 발현하는 균주를 첨가하여 효소처리를 수행할 수 있다.The brewing enzyme may be one or more enzymes selected from the group consisting of pectinase and arabinase, and instead of the brewing enzyme, a strain expressing one or more enzymes selected from the group consisting of pectinase and arabinase is added to treat enzymes. You can do it.
상기 심혈관계 질환은 고혈압, 혈액순환장애 및 동맥경화로 이루어진 군으로부터 선택되는 것일 수 있다.The cardiovascular disease may be selected from the group consisting of hypertension, blood circulation disorder, and arteriosclerosis.
단삼 추출물을 제조함에 있어서, 단삼의 뿌리를 취하고 이를 상온에서 정제수로 깨끗이 세척 및 건조 후 파쇄하되, 이 때 40 내지 50 메쉬(mesh) 사이의 크기가 되도록 하는 것이 바람직하다. 입자의 크기가 작을수록 추출은 용이하나, 여과 과정이 어려워지기 때문이다.In preparing the Danseng extract, the roots of Danseng are taken and crushed after washing and drying with purified water at room temperature, but at this time, it is preferable to have a size of between 40 and 50 mesh. This is because the smaller the particle size, the easier extraction is, but the filtration process becomes difficult.
용매는 파쇄한 분말 무게의 10 내지 20배의 50% 에탄올을 사용하는 것이 바람직하다. 또는 정제수 추출단계와 에탄올 추출단계를 순차적으로 수행할 수 있으나 최종 수율에 큰 영향을 미치지는 않는다. 또한 추출 시 온도는 55 내지 60℃ 사이에서 수행하는 것이 바람직하다. 단삼의 약리성분들 중에 열에 약한 성분들이 존재하기 때문이다. 추출물은 60℃를 넘기지 않는 조건하에서 30 brix까지 감압 농축시켜 이용할 수 있다.It is preferable to use 50% ethanol of 10 to 20 times the weight of the crushed powder as the solvent. Alternatively, the purified water extraction step and the ethanol extraction step may be sequentially performed, but it does not significantly affect the final yield. In addition, it is preferable to perform extraction at a temperature between 55 and 60°C. This is because some of the pharmacological ingredients of Dansam are weak to heat. The extract can be used by concentrating under reduced pressure to 30 brix under conditions not exceeding 60°C.
홍삼 추출물을 제조함에 있어서, 홍삼, 홍미삼 및 백삼을 사용할 수 있으며 4년근 이상의 미삼을 사용하는 것이 바람직하다. 홍삼 추출 시에는 홍삼 무게의 10 내지 20배의 에탄올을 사용한다고 알려져 있으므로 진세노사이드의 추출 수율을 최대로 하기 위해서는 홍삼 무게의 20배의 에탄올을 사용하는 것이 바람직하다. 에탄올 추출은 3차에 걸쳐 수행할 수도 있으나 2차에 걸쳐 수행하는 것이 바람직하다.In preparing the red ginseng extract, red ginseng, red ginseng and white ginseng may be used, and it is preferable to use 4 years or more of ginseng. When extracting red ginseng, it is known that ethanol of 10 to 20 times the weight of red ginseng is used. Therefore, in order to maximize the extraction yield of ginsenoside, it is preferable to use ethanol of 20 times the weight of red ginseng. Ethanol extraction may be performed three times, but is preferably carried out two times.
상기 효소처리 단계는 펙티네이즈 및 아라비네이즈, 또는 펙티네이즈 및 아라비네이즈를 동시 발현하는 균주를 단삼 추출물 및 홍삼 추출물에 첨가하여 제조되는 것일 수 있으나, 이에 한정되는 것은 아니다.The enzymatic treatment step may be prepared by adding pectinase and arabinase, or a strain expressing pectinase and arabinase at the same time, to a sweet ginseng extract and a red ginseng extract, but is not limited thereto.
본 발명의 일 구현예에서, 상기 단삼 및 홍삼 복합효소반응물은 단삼 추출물 및 홍삼 추출물에 펙티네이즈 및 아라비네이즈, 또는 아스페르길루스 니제르(Aspergillus niger var) 균주를 첨가하여 제조될 수 있다.In one embodiment of the present invention, the sweet ginseng and red ginseng complex enzyme reactant may be prepared by adding pectinase and arabinase, or Aspergillus niger var strain to the sweet ginseng extract and red ginseng extract.
효소처리 단계 수행을 위하여 에탄올 추출 시의 중량과 같아지도록 정제수를 첨가할 수 있으나, 이에 한정되는 것은 아니다. 효소의 투여량은 단삼 또는 홍삼 분말 중량의 1 내지 2%일 수 있으며 3%를 넘지 않도록 하는 것이 바람직하다.In order to perform the enzyme treatment step, purified water may be added so as to be the same as the weight at the time of ethanol extraction, but is not limited thereto. The dosage of the enzyme may be 1 to 2% of the weight of the sweet ginseng or red ginseng powder, and it is preferable not to exceed 3%.
상기 효소처리 단계는 20 내지 50℃, 20 내지 45℃, 20 내지 42℃, 28 내지 50℃, 28 내지 45℃, 28 내지 42℃, 32 내지 50℃, 32 내지 45℃, 32 내지 42℃, 40 내지 50℃, 또는 40 내지 45℃, 예를 들어, 40 내지 42℃에서 수행되는 것일 수 있으나, 이에 한정되는 것은 아니다.The enzyme treatment step is 20 to 50 ℃, 20 to 45 ℃, 20 to 42 ℃, 28 to 50 ℃, 28 to 45 ℃, 28 to 42 ℃, 32 to 50 ℃, 32 to 45 ℃, 32 to 42 ℃, It may be performed at 40 to 50°C, or 40 to 45°C, for example, 40 to 42°C, but is not limited thereto.
살비논산 B는 열에 취약하기 때문에 60℃ 이상의 조건에서 효소처리 단계를 수행할 경우 그 양이 급격히 감소할 수 있고, 따라서 60℃ 이하의 저온 조건에서 효소처리 단계를 수행 시 수율을 올릴 수 있다. 단, 40℃ 미만의 온도 조건에서는 반응 시간이 오래 걸릴 수 있다.Since salbinonic acid B is vulnerable to heat, when the enzyme treatment step is performed at a temperature of 60°C or higher, its amount may decrease rapidly, and thus, when the enzyme treatment step is performed at a low temperature condition of 60°C or less, the yield can be increased. However, the reaction time may take a long time under a temperature condition of less than 40°C.
상기 효소처리 단계는 16 내지 36시간, 16 내지 32시간, 16 내지 30시간, 16 내지 25시간, 18 내지 36시간, 18 내지 32시간, 18 내지 30시간, 18 내지 25시간, 20 내지 36시간, 20 내지 32시간 또는 20 내지 30시간, 예를 들어, 20 내지 25시간 동안 수행되는 것일 수 있으나, 이에 한정되는 것은 아니다.The enzyme treatment step is 16 to 36 hours, 16 to 32 hours, 16 to 30 hours, 16 to 25 hours, 18 to 36 hours, 18 to 32 hours, 18 to 30 hours, 18 to 25 hours, 20 to 36 hours, It may be performed for 20 to 32 hours or 20 to 30 hours, for example, 20 to 25 hours, but is not limited thereto.
상기 단삼 및 홍삼 복합효소반응물은 혼합하는 데 있어서, 충분히 교반하여 완전히 섞이도록 하는 것이 바람직하다. 단삼 추출물 및 홍삼 추출물의 중량비를 1:9 내지 9:1, 1:9 내지 7:3, 1:9 내지 6:4, 1:9 내지 5:5, 3:7 내지 9:1, 3:7 내지 7:3 또는 3:7 내지 6:4로 포함하는 것일 수 있고, 예를 들어, 3:7 내지 5:5로 포함하는 것일 수 있으나, 이에 한정되는 것은 아니다.In mixing the sweet ginseng and red ginseng complex enzyme reactants, it is preferable to sufficiently agitate them so that they are completely mixed. The weight ratio of the sweet ginseng extract and the red ginseng extract is 1:9 to 9:1, 1:9 to 7:3, 1:9 to 6:4, 1:9 to 5:5, 3:7 to 9:1, 3: 7 to 7:3 or 3:7 to 6:4 may be included, for example, may be included in 3:7 to 5:5, but is not limited thereto.
상기 생물전환 단계에 있어서, 미생물 배양액은 트리코데르마 레에세이, 아스퍼질러스 오리제, 비피도박테리움 롱검 또는 락토바실러스 람노서스로 이루어진 군으로부터 선택되는 1종 이상의 균주의 배양액인 것일 수 있으며, 예를 들어, 트리코데르마 레에세이 균주의 배양액인 것일 수 있으나, 이에 한정되는 것은 아니다.In the biotransformation step, the microbial culture medium may be a culture medium of one or more strains selected from the group consisting of Trichoderma reessay, Aspergillus oris, Bifidobacterium longum, or Lactobacillus rhamnosus, for example For example, it may be a culture medium of the Trichoderma Reessay strain, but is not limited thereto.
상기 단삼 및 홍삼 복합효소반응물의 100 중량부에 대하여 미생물 배양액은 1 내지 5 중량부를 첨가하고, 40 내지 45℃에서 50 내지 80시간 동안 반응시키는 것일 수 있으며, 이후 70 내지 100℃에서 40 내지 80분 동안 가열하여 생물전환공정을 종료시키는 것일 수 있으나, 이에 한정되는 것은 아니다.Microbial culture solution may be added 1 to 5 parts by weight, and reacted at 40 to 45°C for 50 to 80 hours, and then at 70 to 100°C for 40 to 80 minutes with respect to 100 parts by weight of the Dansam and Red Ginseng complex enzyme reactants. While heating may be performed to terminate the bioconversion process, it is not limited thereto.
본 발명의 또 다른 양태는 단삼 생물전환 추출물 및 홍삼 생물전환 추출물을 포함하는 심혈관계 질환 개선용 식품 조성물이다.Another aspect of the present invention is a food composition for improving cardiovascular disease comprising a biotransformation extract of dansam and red ginseng biotransformation extract.
상기 단삼 생물전환 추출물 및 홍삼 생물전환 추출물은 각각 생물전환 공정을 실시하여 추출물을 제조한 후 혼합할 수 있고, 단삼 및 홍삼 추출물을 생물전환 공정을 실시하여 제조한 것을 이용할 수도 있다.The single ginseng bioconversion extract and the red ginseng bioconversion extract may be mixed after preparing an extract by performing a bioconversion process, respectively, and those prepared by performing a bioconversion process of a single ginseng and red ginseng extract may be used.
상기 단삼 생물전환 추출물 및 홍삼 생물전환 추출물은 단삼 효소반응물 및 홍삼 효소반응물에 미생물 배양액을 첨가하여 제조된 것일 수 있다.The single ginseng bioconversion extract and red ginseng bioconversion extract may be prepared by adding a microbial culture solution to a single ginseng enzyme reaction product and a red ginseng enzyme reaction product.
상기 심혈관계 질환은 고혈압, 혈액순환장애 및 동맥경화로 이루어진 군으로부터 선택되는 것일 수 있다.The cardiovascular disease may be selected from the group consisting of hypertension, blood circulation disorder, and arteriosclerosis.
상기 단삼 및 홍삼 복합효소반응물은 단삼 추출물 및 홍삼 추출물에 양조 효소를 첨가하여 제조되는 것일 수 있고, 펙티네이즈 및 아라비네이즈로 이루어진 군으로부터 선택되는 1종 이상의 효소, 또는 이를 발현하는 균주를 단삼 추출물 및 홍삼 추출물에 첨가하여 제조되는 것일 수 있으며, 예를 들어, 펙티네이즈 및 아라비네이즈, 또는 이를 동시 발현하는 균주를 단삼 추출물 및 홍삼 추출물에 첨가하여 제조되는 것일 수 있으나, 이에 한정되는 것은 아니다.The sweet ginseng and red ginseng complex enzyme reactant may be prepared by adding a brewing enzyme to the sweet ginseng extract and red ginseng extract, and at least one enzyme selected from the group consisting of pectinase and arabinase, or a strain expressing the same may be used as a sweet ginseng extract and It may be prepared by adding to the red ginseng extract, for example, pectinase and arabinase, or a strain expressing the same may be added to the sweet ginseng extract and the red ginseng extract, but is not limited thereto.
본 발명의 일 구현예에서, 상기 단삼 및 홍삼 복합효소반응물은 단삼 추출물 및 홍삼 추출물에 펙티네이즈 및 아라비네이즈, 또는 아스페르길루스 니제르 균주를 첨가하여 제조될 수 있다.In one embodiment of the present invention, the sweet ginseng and red ginseng complex enzyme reactant may be prepared by adding pectinase and arabinase, or Aspergillus niger strain to the sweet ginseng extract and red ginseng extract.
상기 단삼 및 홍삼 복합효소반응물은 단삼 추출물 및 홍삼 추출물의 중량비를 1:9 내지 9:1, 1:9 내지 7:3, 1:9 내지 6:4, 1:9 내지 5:5, 3:7 내지 9:1, 3:7 내지 7:3 또는 3:7 내지 6:4로 포함하는 것일 수 있고, 예를 들어, 3:7 내지 5:5로 포함하는 것일 수 있으나, 이에 한정되는 것은 아니다.The single ginseng and red ginseng complex enzyme reactants are 1:9 to 9:1, 1:9 to 7:3, 1:9 to 6:4, 1:9 to 5:5, 3: It may be included in 7 to 9:1, 3:7 to 7:3 or 3:7 to 6:4, for example, it may be included in 3:7 to 5:5, but is limited thereto no.
상기 단삼 및 홍삼 복합효소반응물은 단삼 추출물 및 홍삼 추출물에 각각 효소처리 공정을 실시하여 수득한 효소반응물을 혼합하여 제조할 수 있고, 단삼 추출물 및 홍삼 추출물을 혼합한 복합추출물에 효소처리 공정을 실시하여 제조할 수도 있다.The sweet ginseng and red ginseng complex enzyme reactants can be prepared by mixing the enzyme reactants obtained by performing an enzyme treatment process on the sweet ginseng extract and the red ginseng extract, respectively, and by performing an enzyme treatment process on the complex extract obtained by mixing the sweet ginseng extract and the red ginseng extract. It can also be manufactured.
상기 단삼 추출물은 30 내지 80%(w/w), 30 내지 75%(w/w), 30 내지 70%(w/w), 30 내지 65%(w/w), 30 내지 60%(w/w), 30 내지 55%(w/w), 40 내지 80%(w/w), 40 내지 75%(w/w), 40 내지 70%(w/w), 40 내지 65%(w/w) 또는 40 내지 60%(w/w)의 에탄올을 용매로 하여 수득되는 것일 수 있고, 예를 들어, 40 내지 55%(w/w)의 에탄올을 용매로 하여 수득되는 것일 수 있으나, 이에 한정되는 것은 아니다.The Dansam extract is 30 to 80% (w/w), 30 to 75% (w/w), 30 to 70% (w/w), 30 to 65% (w/w), 30 to 60% (w /w), 30 to 55% (w/w), 40 to 80% (w/w), 40 to 75% (w/w), 40 to 70% (w/w), 40 to 65% (w /w) or 40 to 60% (w / w) of ethanol may be obtained as a solvent, for example, 40 to 55% (w / w) of ethanol may be obtained as a solvent, It is not limited thereto.
상기 홍삼 추출물은 30 내지 80%(w/w), 30 내지 75%(w/w), 30 내지 70%(w/w), 30 내지 65%(w/w), 30 내지 60%(w/w), 30 내지 55%(w/w), 40 내지 80%(w/w), 40 내지 75%(w/w), 40 내지 70%(w/w), 40 내지 65%(w/w) 또는 40 내지 60%(w/w)의 에탄올을 용매로 하여 수득되는 것일 수 있고, 예를 들어, 40 내지 55%(w/w)의 에탄올을 용매로 하여 수득되는 것일 수 있으나, 이에 한정되는 것은 아니다.The red ginseng extract is 30 to 80% (w / w), 30 to 75% (w / w), 30 to 70% (w / w), 30 to 65% (w / w), 30 to 60% (w /w), 30 to 55% (w/w), 40 to 80% (w/w), 40 to 75% (w/w), 40 to 70% (w/w), 40 to 65% (w /w) or 40 to 60% (w / w) of ethanol may be obtained as a solvent, for example, 40 to 55% (w / w) of ethanol may be obtained as a solvent, It is not limited thereto.
상기 미생물 배양액은 트리코데르마 레에세이, 아스퍼질러스 오리제, 비피도박테리움 롱검 또는 락토바실러스 람노서스로 이루어진 군으로부터 선택되는 1종 이상의 균주의 배양액인 것일 수 있으며, 예를 들어, 트리코데르마 레에세이 균주의 배양액인 것일 수 있으나, 이에 한정되는 것은 아니다.The microbial culture medium may be a culture medium of one or more strains selected from the group consisting of Trichoderma reessay, Aspergillus oris, Bifidobacterium longum, or Lactobacillus rhamnosus, for example, Trichoderma It may be a culture medium of the Reessay strain, but is not limited thereto.
본 발명의 또 다른 양태는 다음 단계를 포함하는, 단삼 생물전환 추출물 및 홍삼 생물전환 추출물을 포함하는 심혈관계 질환 개선용 식품의 제조방법이다:Another aspect of the present invention is a method for preparing a food for improving cardiovascular diseases comprising the biotransformation extract and red ginseng biotransformation extract comprising the following steps:
단삼 추출물 및 홍삼 추출물에 양조 효소를 첨가하여 단삼 효소반응물 및 홍삼 효소반응물을 제조하는 효소처리 단계; 및Enzymatic treatment step of preparing a sweet ginseng enzyme reaction product and a red ginseng enzyme reaction product by adding a brewing enzyme to the sweet ginseng extract and the red ginseng extract; And
상기 단삼 효소반응물 및 홍삼 효소반응물에 미생물 배양액을 반응시켜 단삼 생물전환 추출물 및 홍삼 생물전환 추출물을 제조하는 생물전환 단계.A bioconversion step of reacting a microbial culture solution with the enzyme reaction product of Dansam and the enzyme reaction of red ginseng to prepare a bioconversion extract and a bioconversion extract of red ginseng.
상기 방법은 효소처리 단계 이후에 양조 효소를 불활성화 시키는 불활성화 단계를 추가적으로 포함할 수 있다. 상술한 바와 같은 불활성화 단계의 실시에 의해 컴파운드 K가 전환되는 것을 방지할 수 있다.The method may further include an inactivation step of inactivating the brewing enzyme after the enzyme treatment step. Conversion of compound K can be prevented by performing the inactivation step as described above.
상기 양조 효소는 펙티네이즈 및 아라비네이즈로 이루어진 군으로부터 선택되는 1종 이상의 효소일 수 있고, 양조 효소 대신 펙티네이즈 및 아라비네이즈로 이루어진 군으로부터 선택되는 1종 이상의 효소를 발현하는 균주를 첨가하여 효소처리를 수행할 수 있다.The brewing enzyme may be one or more enzymes selected from the group consisting of pectinase and arabinase, and instead of the brewing enzyme, a strain expressing one or more enzymes selected from the group consisting of pectinase and arabinase is added to treat enzymes. You can do it.
상기 심혈관계 질환은 고혈압, 혈액순환장애 및 동맥경화로 이루어진 군으로부터 선택되는 것일 수 있으나, 이에 한정되는 것은 아니다.The cardiovascular disease may be selected from the group consisting of high blood pressure, blood circulation disorder, and arteriosclerosis, but is not limited thereto.
상기 효소처리 단계는 펙티네이즈 및 아라비네이즈, 또는 펙티네이즈 및 아라비네이즈를 동시 발현하는 균주를 단삼 추출물 및 홍삼 추출물에 첨가하여 제조되는 것일 수 있으나, 이에 한정되는 것은 아니다.The enzymatic treatment step may be prepared by adding pectinase and arabinase, or a strain expressing pectinase and arabinase at the same time, to a sweet ginseng extract and a red ginseng extract, but is not limited thereto.
본 발명의 일 구현예에서, 상기 단삼 및 홍삼 복합효소반응물은 단삼 추출물 및 홍삼 추출물에 펙티네이즈 및 아라비네이즈, 또는 아스페르길루스 니제르(Aspergillus niger var) 균주를 첨가하여 제조될 수 있다.In one embodiment of the present invention, the sweet ginseng and red ginseng complex enzyme reactant may be prepared by adding pectinase and arabinase, or Aspergillus niger var strain to the sweet ginseng extract and red ginseng extract.
상기 효소처리 단계는 20 내지 50℃, 20 내지 45℃, 20 내지 42℃, 28 내지 50℃, 28 내지 45℃, 28 내지 42℃, 32 내지 50℃, 32 내지 45℃, 32 내지 42℃, 40 내지 50℃, 또는 40 내지 45℃, 예를 들어, 40 내지 42℃에서 수행되는 것일 수 있으나, 이에 한정되는 것은 아니다.The enzyme treatment step is 20 to 50 ℃, 20 to 45 ℃, 20 to 42 ℃, 28 to 50 ℃, 28 to 45 ℃, 28 to 42 ℃, 32 to 50 ℃, 32 to 45 ℃, 32 to 42 ℃, It may be performed at 40 to 50°C, or 40 to 45°C, for example, 40 to 42°C, but is not limited thereto.
상기 효소처리 단계는 16 내지 36시간, 16 내지 32시간, 16 내지 30시간, 16 내지 25시간, 18 내지 36시간, 18 내지 32시간, 18 내지 30시간, 18 내지 25시간, 20 내지 36시간, 20 내지 32시간 또는 20 내지 30시간, 예를 들어, 20 내지 25시간 동안 수행되는 것일 수 있으나, 이에 한정되는 것은 아니다.The enzyme treatment step is 16 to 36 hours, 16 to 32 hours, 16 to 30 hours, 16 to 25 hours, 18 to 36 hours, 18 to 32 hours, 18 to 30 hours, 18 to 25 hours, 20 to 36 hours, It may be performed for 20 to 32 hours or 20 to 30 hours, for example, 20 to 25 hours, but is not limited thereto.
상기 단삼 및 홍삼 복합효소반응물은 단삼 추출물 및 홍삼 추출물의 중량비를 1:9 내지 9:1, 1:9 내지 7:3, 1:9 내지 6:4, 1:9 내지 5:5, 3:7 내지 9:1, 3:7 내지 7:3 또는 3:7 내지 6:4로 포함하는 것일 수 있고, 예를 들어, 3:7 내지 5:5로 포함하는 것일 수 있으나, 이에 한정되는 것은 아니다.The single ginseng and red ginseng complex enzyme reactants are 1:9 to 9:1, 1:9 to 7:3, 1:9 to 6:4, 1:9 to 5:5, 3: It may be included in 7 to 9:1, 3:7 to 7:3 or 3:7 to 6:4, for example, it may be included in 3:7 to 5:5, but is limited thereto no.
상기 미생물 배양액은 트리코데르마 속 균주의 배양액인 것일 수 있으며, 예를 들어, 트리코데르마 레에세이, 아스퍼질러스 오리제, 비피도박테리움 롱검 또는 락토바실러스 람노서스로 이루어진 군으로부터 선택되는 1종 이상의 균주의 배양액인 것일 수 있으며, 예를 들어, 트리코데르마 레에세이 균주의 배양액인 것일 수 있으나, 이에 한정되는 것은 아니다.The microbial culture medium may be a culture medium of a strain of the genus Trichoderma, for example, one selected from the group consisting of Trichoderma reessay, Aspergillus oris, Bifidobacterium longum, or Lactobacillus rhamnosus It may be a culture solution of the above strain, for example, may be a culture solution of the Trichoderma Reessay strain, but is not limited thereto.
본 발명은 단삼(Salvia miltiorrhiza) 생물전환 추출물 및 홍삼(red ginseng) 생물전환 추출물을 포함하는 심혈관계 질환 예방 또는 치료용 조성물에 관한 것으로서, 상기 단삼 추출물 및 홍삼 추출물에 효소처리 후 트리코데르마 레에세이(Trichoderma reesei) 배양액을 반응시켜 제조한 생물전환 복합추출물은 내피세포의 활성을 높이고 염증을 억제하는 효과가 있으므로, 이를 효과적으로 심혈관계 질환의 예방 또는 치료에 이용할 수 있다.The present invention relates to a composition for preventing or treating cardiovascular diseases comprising a Salvia miltiorrhiza biotransformation extract and a red ginseng biotransformation extract, wherein the trichoderma reessay after enzymatic treatment of the dansam extract and red ginseng extract ( Trichoderma reesei ) Since the biotransformation complex extract prepared by reacting the culture medium has the effect of increasing the activity of endothelial cells and suppressing inflammation, it can be effectively used for the prevention or treatment of cardiovascular diseases.
도 1은 본 발명의 실시예에 따른 생물전환 복합추출물 제조공정을 나타내는 다이어그램이다.
도 2는 본 발명의 실시예에 따른 생물전환 복합추출물의 컴파운드(Compound) K 함량분석실험의 고성능 액체 크로마토그래피(high-performance liquid chromatography; HPLC) 데이터를 나타낸 그래프이다.
도 3은 본 발명의 실시예에 따른 생물전환 복합추출물의 내피세포 활성에 대한 MTT 분석 결과를 나타낸 그래프이다.
도 4는 본 발명의 실시예에 따른 생물전환 복합추출물의 IL-6 발현 억제 효과에 관한 ELISA 실험 결과를 나타낸 그래프이다.
도 5는 본 발명의 실시예에 따른 생물전환 복합추출물의 IL-8 발현 억제 효과에 관한 ELISA 실험 결과를 나타낸 그래프이다.
도 6은 본 발명의 실시예에 따른 생물전환 복합추출물의 TNF-α 발현 억제 효과에 관한 ELISA 실험 결과를 나타낸 그래프이다.
도 7은 본 발명의 실시예에 따른 생물전환 복합추출물의 DPPH 라디칼(radical) 소거능 실험 결과를 나타낸 그래프이다.
도 8은 본 발명의 실시예에 따른 생물전환 복합추출물의 ABTs 라디칼 소거능 실험 결과를 그래프로 나타낸 그래프이다.
도 9는 본 발명의 실시예에 따른 생물전환 복합추출물의 LDL 산화(oxidation) 억제 활성 측정 실험 결과를 나타낸 그래프이다.
도 10은 본 발명의 실시예에 따른 생물전환 복합추출물의 ox-LDL 업테이크(up take) 억제 활성 측정 실험 결과를 나타낸 그림이다.
도 11은 본 발명의 실시예에 따른 단삼 추출물 및 단삼 생물전환 복합추출물의 혈압조절 효과를 나타낸 그래프이다.
도 12는 본 발명의 실시예에 따른 홍삼 추출물 및 홍삼 생물전환 복합추출물의 혈압조절 효과를 나타낸 그래프이다.
도 13은 본 발명의 실시예에 따른 단삼 및 홍삼 효소반응물 및 단삼 및 홍삼 생물전환 복합추출물의 혈압조절 효과를 나타낸 그래프이다.1 is a diagram showing a manufacturing process of a bioconversion complex extract according to an embodiment of the present invention.
2 is a graph showing high-performance liquid chromatography (HPLC) data of a compound K content analysis experiment of a bioconversion complex extract according to an embodiment of the present invention.
3 is a graph showing the results of MTT analysis on endothelial cell activity of a biotransformation complex extract according to an embodiment of the present invention.
4 is a graph showing the results of an ELISA experiment on the inhibitory effect of IL-6 expression of a biotransformation complex extract according to an embodiment of the present invention.
5 is a graph showing the results of an ELISA experiment on the effect of inhibiting IL-8 expression of a biotransformation complex extract according to an embodiment of the present invention.
6 is a graph showing the results of an ELISA experiment on the inhibitory effect of TNF-α expression of the biotransformation complex extract according to an embodiment of the present invention.
7 is a graph showing the DPPH radical scavenging ability test results of the bioconversion complex extract according to an embodiment of the present invention.
8 is a graph showing the experimental results of ABTs radical scavenging ability of a bioconversion complex extract according to an embodiment of the present invention.
9 is a graph showing the results of an experiment for measuring LDL oxidation inhibitory activity of a bioconversion complex extract according to an embodiment of the present invention.
10 is a diagram showing the results of an experiment for measuring ox-LDL uptake inhibitory activity of a bioconversion complex extract according to an embodiment of the present invention.
11 is a graph showing the blood pressure control effect of the Dansam extract and the Dansam bioconversion complex extract according to an embodiment of the present invention.
12 is a graph showing the blood pressure control effect of red ginseng extract and red ginseng bioconversion complex extract according to an embodiment of the present invention.
13 is a graph showing the blood pressure control effect of the enzyme reaction products of sweet ginseng and red ginseng and the bioconversion complex extract of sweet ginseng and red ginseng according to an embodiment of the present invention.
이하, 본 발명을 하기의 실시예에 의하여 더욱 상세히 설명한다. 그러나 이들 실시예는 본 발명을 예시하기 위한 것일 뿐이며, 본 발명의 범위가 이들 실시예에 의하여 한정되는 것은 아니다.Hereinafter, the present invention will be described in more detail by the following examples. However, these examples are for illustrative purposes only, and the scope of the present invention is not limited by these examples.
본 명세서 전체에 걸쳐, 특정 물질의 농도를 나타내기 위하여 사용되는 "%"는 별도의 언급이 없는 경우, 고체/고체는 (중량/중량)%, 고체/액체는 (중량/부피)%, 그리고 액체/액체는 (부피/부피)%이다.Throughout this specification, "%" used to indicate the concentration of a specific substance is (weight/weight)% for solids/solids, (weight/volume)% for solids/liquids, and Liquid/liquid is (vol/vol)%.
실시예 1: 생물전환 복합추출물의 제조Example 1: Preparation of biotransformation complex extract
1-1. 단삼 효소반응물의 제조1-1. Preparation of enzyme reaction product of Danshen
단삼의 뿌리 50 kg을 구입하여, 정제수로 잔존 토양을 제거하여 깨끗하게 세척 후 40 내지 50℃에서 온풍 건조하여 파쇄하였다. 파쇄된 단삼근 분말 45 kg에 대하여, 50% 에탄올을 900 L 첨가하여 55℃에서 72시간 동안 추출함으로써 에탄올 추출물을 제조하고, 이를 여과 없이 30 brix까지 감압 농축하였다.50 kg of the roots of Danseng were purchased, the residual soil was removed with purified water, washed, and then crushed by drying with warm air at 40 to 50°C. With respect to 45 kg of the crushed ginseng root powder, 900 L of 50% ethanol was added and extracted for 72 hours at 55°C to prepare an ethanol extract, which was concentrated under reduced pressure to 30 brix without filtration.
이후 정제수를 첨가하여 10배 희석하고, 희석액에 Gluc gin(제조사: Higusi Moyashi, 효소종류: Pectinase and Arabinase, 효소생산 미생물: Aspergillus niger var)을 희석액 중량 대비 2 내지 3% 첨가하였다. 상기 반응은 50 내지 55℃에서 24시간 동안 수행하였다.Then, purified water was added to dilute 10 times, and Gluc gin (manufacturer: Higusi Moyashi, enzyme type: Pectinase and Arabinase, enzyme producing microorganism: Aspergillus niger var) was added 2 to 3% by weight of the diluted solution. The reaction was carried out at 50 to 55° C. for 24 hours.
반응물은 90℃에서 1시간 동안 가열하여 잔존효소를 불활성화시키고, 반응물을 30 brix까지 감압 농축하였다. 농축액에서 생리활성물질인 살비논산 B(salvianolic acid B)의 함량을 분석한 후 결과에 따라 최종 농도가 2 mg/ml 이 되도록 정제수로 희석하였다.The reaction product was heated at 90° C. for 1 hour to inactivate the residual enzyme, and the reaction product was concentrated under reduced pressure to 30 brix. After analyzing the content of the physiologically active substance salvianolic acid B in the concentrate, it was diluted with purified water so that the final concentration was 2 mg/ml.
1-2. 홍삼 효소반응물의 제조1-2. Preparation of red ginseng enzyme reactant
실시예 1-1과 동일하게 수행하되, 단삼 대신 홍삼을 이용하여 제조하였다. 농축액에서는 Rb1의 최종 농도가 2 mg/ml 이 되도록 정제수로 희석하였다.It was carried out in the same manner as in Example 1-1, but was prepared using red ginseng instead of sweet ginseng. In the concentrate, it was diluted with purified water so that the final concentration of Rb1 was 2 mg/ml.
1-3. 트리코데르마 레에세이 배양액의 제조1-3. Preparation of Trichoderma Reessay culture solution
트리코데르마 레에세이(Trichoderma reesei) 균주를 30℃ 액체 배지(YM broth: Yeast Extract 3 g, Malt Extract 3 g, Peptone 5 g, Dextrose 10 g을 정제수 1 리터에 녹임)에서 24시간 동안 배양한 후, 원심분리를 통하여 상층액을 취하고, 염석법(salting out)을 1회 수행하고 얻은 반응액을 여과하여(pore size 0.22 ㎛) 배양액을 얻었다.After incubating the Trichoderma reesei strain in a 30°C liquid medium (YM broth: Yeast Extract 3 g, Malt Extract 3 g, Peptone 5 g, Dextrose 10 g dissolved in 1 liter of purified water) for 24 hours , The supernatant was taken through centrifugation, salting out was performed once, and the obtained reaction solution was filtered (pore size 0.22 µm) to obtain a culture solution.
1-4. 단삼 및 홍삼 생물전환 복합추출물의 제조1-4. Preparation of bioconversion complex extracts of sweet and red ginseng
실시예 1-1 및 1-2의 효소반응물을 0:10, 3:7, 4:6, 5:5, 6:4, 7:3 및 10:0의 다양한 중량비로 혼합하였다. 이후 단삼 및 홍삼의 효소반응물 100 중량부 대비 실시예 1-3의 트리코데르마 레에세이(Trichoderma reesei)의 배양액 2 중량부를 첨가하여 40 내지 45℃에서 72시간 동안 반응시켜 생물전환하였다. 이후 반응물을 90℃에서 1시간 동안 가열함으로써 잔존효소를 불활성화시키고 생물전환공정을 종료시켰다. 상기 제조된 단삼 및 홍삼 생물전환 복합추출물을 40 내지 50℃로 냉각한 후 퍼라이트(perlite)를 이용하여 여과하였다. 상기 여과액은 70 brix까지 감압 농축하여 최종 결과물(hyperfree)을 수득하였다.The enzyme reaction products of Examples 1-1 and 1-2 were mixed in various weight ratios of 0:10, 3:7, 4:6, 5:5, 6:4, 7:3 and 10:0. Thereafter, 2 parts by weight of the culture solution of Trichoderma reesei of Example 1-3 was added to 100 parts by weight of the enzyme reaction products of sweet ginseng and red ginseng, followed by reaction at 40 to 45° C. for 72 hours to bioconvert. Thereafter, the reaction was heated at 90° C. for 1 hour to inactivate the residual enzyme and terminate the bioconversion process. The prepared sweet ginseng and red ginseng bioconversion complex extract was cooled to 40 to 50°C, and then filtered using perlite. The filtrate was concentrated under reduced pressure to 70 brix to obtain a final product (hyperfree).
실시예 2: 단삼 및 홍삼 생물전환 복합추출물의 컴파운드 K 함량 확인Example 2: Confirmation of compound K content of bioconversion complex extracts of sweet ginseng and red ginseng
본 발명의 실시예에 따라 제조된 단삼 및 홍삼 생물전환 복합추출물과, 효소처리 공정 및 생물전환 공정 중 어느 것도 진행하지 않은 복합추출물을 각각 100배 희석하여 아래 표 1과 같은 조건으로 고성능 액체 크로마토그래피(high-performance liquid chromatography, HPLC)를 통하여 컴파운드 K의 함량을 비교하였다.High-performance liquid chromatography under the conditions shown in Table 1 below by diluting the complex extracts for bioconversion of sweet ginseng and red ginseng prepared according to an embodiment of the present invention, and the complex extracts that have not undergone any of the enzyme treatment and bioconversion processes, respectively. The content of compound K was compared through (high-performance liquid chromatography, HPLC).
도 2에서 확인할 수 있듯이, 생물전환공정을 진행하지 않은 경우의 효소반응물에서는 컴파운드 K가 확인되지 않았고, 상기 방법을 통하여 생물전환공정을 수행한 단삼 및 홍삼 생물전환 복합추출물 에서는 17.3 mg/g의 컴파운드 K 함량이 확인되었다.As can be seen in FIG. 2, compound K was not confirmed in the enzyme reaction product when the bioconversion process was not performed, and 17.3 mg/g of the compound in the bioconversion complex extract of sweet ginseng and red ginseng which was subjected to the bioconversion process through the above method. The K content was confirmed.
실시예 3: 단삼 및 홍삼 생물전환 복합추출물에서의 내피세포 활성 효과 확인Example 3: Confirmation of the effect of endothelial cell activity in the bioconversion complex extract of sweet ginseng and red ginseng
미리 24 웰 플레이트(well plate)에 웰 당 20,000 개의 내피세포를(Human Umbilical Vein Endothelial Cells, Single Donor, LONZA) 분주한 다음 CO2 인큐베이터(incubator)에서 EGM-2 배지를 사용하여 24시간 동안 배양한 후, 배양한 내피세포에 실시예 1-4에서 준비한 단삼과 홍삼의 조성을 달리한 시료들을 처리하였다.In advance, 20,000 endothelial cells per well (Human Umbilical Vein Endothelial Cells, Single Donor, LONZA) were dispensed in a 24-well plate, and then cultured for 24 hours using EGM-2 medium in a CO 2 incubator. Thereafter, the cultured endothelial cells were treated with samples having different compositions of sweet ginseng and red ginseng prepared in Example 1-4.
이 때 각 단계별 시료들은 각각 50배로 희석하여 각 웰에 투여하고, 24시간 동안 추가 배양하였다. 각 웰의 배지 성분은 버리고 남은 세포들을 MTT 분석법을 사용하여 대조군(Control)의 세포생존율(cell viability)을 기준으로 하여 다른 실험군들의 세포생존율을 퍼센트로 나타내었다.At this time, each step sample was diluted 50 times, administered to each well, and further cultured for 24 hours. The media components of each well were discarded and the remaining cells were expressed as percentages of the cell viability of the other experimental groups based on the cell viability of the control group using the MTT assay.
도 3에서 확인할 수 있듯이, 해당 농도에서 각각의 시료들은 혈관내피세포에 대하여 독성을 보이지 않았을 뿐만 아니라 오히려 세포의 활성 유도에 도움이 되었다.As can be seen in FIG. 3, each sample at the corresponding concentration did not show toxicity to vascular endothelial cells, but rather helped induce cell activity.
실시예 4: 단삼 및 홍삼 생물전환 복합추출물에서의 내피세포 염증 억제 효과 확인Example 4: Confirmation of the endothelial cell inflammation inhibition effect in the biotransformation complex extract of sweet ginseng and red ginseng
24 웰 플레이트에 웰 당 20,000 개의 내피세포를 분주한 다음 CO2 인큐베이터에서 24시간 동안 배양한 후, 염증유발 대조군으로서 LPS를 첨가한 다음 24시간 동안 추가로 배양하였고, 상기와 같은 방법으로 제조된 단삼 및 홍삼 생물전환 복합추출물 및 생물전환 기술이 적용되지 않은 단삼 및 홍삼 효소반응물을 준비하였다.After dispensing 20,000 endothelial cells per well in a 24-well plate and incubating for 24 hours in a CO 2 incubator, LPS was added as an inflammation-inducing control, followed by additional culture for 24 hours, and Danseng prepared in the same manner as above. And red ginseng biotransformation complex extracts and sweet ginseng and red ginseng enzyme reactants to which bioconversion technology was not applied were prepared.
두 종류의 실험군은 각각 단삼과 홍삼의 함량비를 달리하여 각 웰에 0.5 ml씩(배지 9.5 ml) 투여하고, 다시 24시간 동안 배양한 후 각 실험군의 세포배양액을 모아, 염증을 유발한 내피세포에서의 대표적인 염증 바이오마커(inflammation bio-maker)인 인터류킨(Interleukin) 6과 인터류킨 8의 분비 농도 변화를 ELISA법으로 측정하여 염증 완화 효과 유무를 분석하였다.Each of the two experimental groups was administered 0.5 ml (9.5 ml of medium) to each well at different content ratios of sweet and red ginseng, and cultured again for 24 hours, and then the cell culture solution of each experimental group was collected and endothelial cells causing inflammation. The changes in the secretion concentrations of
도 4, 5 및 표 2에서 확인할 수 있듯이, 효소처리 공정 및 생물전환 공정 중 어느 것도 진행하지 않은 복합추출물을 처리한 실험군에서, 대조군에 비하여 IL-6 및 IL-8의 발현량이 약 5 내지 20% 감소하였고 특히 단삼과 홍삼 추출물의 비율이 4:6 또는 5:5인 경우에 다른 비율로 적용한 경우에 비해 발현량이 현저하게 감소하였다.As can be seen in Figures 4, 5 and Table 2, in the experimental group treated with the complex extract in which neither of the enzyme treatment process nor the bioconversion process proceeded, the expression levels of IL-6 and IL-8 were about 5 to 20 compared to the control group. % Decreased, and in particular, when the ratio of sweet ginseng and red ginseng extract was 4:6 or 5:5, the expression level decreased significantly compared to the case of applying other ratios.
Il-8 발현량 (%)Biotransformation Complex Extract
Il-8 expression level (%)
그러나 모든 비율의 단삼 및 홍삼 생물전환 복합추출물에서 적게는 20%, 많게는 50% 이상 IL-6 및 IL-8의 발현량이 감소하였으며, 특히 생물전환 공정을 수행한 경우가 그렇지 않은 경우보다 IL-6 및 IL-8의 발현량이 두드러지게 높았다.단삼 및 홍삼 생물전환 복합추출물의 비율은 4:6 인 경우 가장 높은 IL-6 및 IL-8 발현 억제를 보였으며, 이는 두 추출물에 포함된 약리 활성 성분들이 서로 시너지 효과를 나타냈기 때문인 것으로 보인다.However, the expression levels of IL-6 and IL-8 decreased by at least 20%, and at most 50% or more in all ratios of the single ginseng and red ginseng biotransformation complex extracts, especially when the bioconversion process was performed compared to the other cases. And IL-8 expression levels were remarkably high. When the ratio of the biotransformation complex extract of sweet and red ginseng was 4:6, the highest inhibition of IL-6 and IL-8 expression was shown, which is a pharmacologically active ingredient contained in both extracts. This seems to be because they showed synergies with each other.
실시예 5: 단삼 및 홍삼 생물전환 복합추출물의 TNF-α 발현 억제 효과 확인Example 5: Confirmation of TNF-α expression inhibitory effect of biotransformation complex extract of sweet ginseng and red ginseng
24 웰 플레이트에 웰 당 20,000 개의 RAW264.7 세포를 분주한 다음 CO2 인큐베이터에서 24시간 동안 배양한 후, 염증유발 대조군으로서 LPS를 첨가한 다음 24시간 동안 추가로 배양하였고, 상기와 같은 방법으로 제조된 단삼 및 홍삼 생물전환 복합추출물과 효소처리 공정 및 생물전환 공정 중 어느 것도 진행하지 않은 복합추출물을 준비하였다.After dispensing 20,000 RAW264.7 cells per well into a 24-well plate, incubating for 24 hours in a CO 2 incubator, LPS was added as an inflammation-inducing control, and then further cultured for 24 hours, prepared in the same manner as above. The prepared sweet and red ginseng bioconversion complex extract and the enzyme treatment and bioconversion complex extract were prepared.
두 종류의 실험군에서 각각 단삼과 홍삼의 조성비를 달리 설정하여 각 웰에 0.5 ml씩(배지 9.5 ml)투여하고, 다시 24시간 동안 배양한 후 각 실험군의 세포배양액을 모아, 염증을 유발한 내피세포에서의 대표적인 염증 바이오마커인 TNF-α(tumor necrosis factor-alpha) 분비 농도 변화를 ELISA 법으로 측정하여 염증 완화 효과 유무를 실험하였다.In the two experimental groups, the composition ratios of single ginseng and red ginseng were set differently, and 0.5 ml (9.5 ml of medium) was administered to each well, and after culturing for 24 hours, the cell culture solution of each experimental group was collected, and the endothelial cells causing inflammation The change in the secretion concentration of TNF-α (tumor necrosis factor-alpha), a representative inflammatory biomarker in, was measured by ELISA to test the presence or absence of the inflammation alleviating effect.
도 6 및 표 3에서 확인할 수 있듯이, 상기 실시예 4에서와 거의 유사한 형태의 결과가 도출되었다.As can be seen in Fig. 6 and Table 3, a result of a form almost similar to that in Example 4 was derived.
먼저 단삼 및 홍삼 복합추출물 실험군에서는 모든 구간에서 TNF-α 발현양이 20% 이상 감소하였고 특히 4:6, 5:5 비율의 조성비에서 가장 많은 감소량을 보였다. 단삼 및 홍삼 생물전환 복합추출물의 경우에는 모든 실험군에서 50% 이상 TNF-α 발현양이 감소한 것을 확인하였으며, 특별하게는 4:6의 비율을 적용한 시료에서 가장 많은 감소량을 보였다.First, in the experimental group of sweet ginseng and red ginseng extracts, the amount of TNF-α expression decreased by more than 20% in all sections, and the most decreased in the composition ratio of 4:6 and 5:5. In the case of the biotransformation complex extract of sweet ginseng and red ginseng, it was confirmed that the amount of TNF-α expression decreased by 50% or more in all experimental groups, and in particular, the most decreased amount in the sample to which the ratio of 4:6 was applied.
실시예 6: 단삼 및 홍삼 생물전환 복합추출물의 DPPH 라디칼 소거능 측정Example 6: Measurement of DPPH radical scavenging ability of bioconversion complex extracts of sweet ginseng and red ginseng
DPPH(1,1-diphenyl-2-picrylhydrazyl, sigma) 라디칼 소거활성은 Blois방법을 사용하여 측정하였다. DPPH 0.15 mM을 에탄올 원액(absolute ethanol) 100 mL에 용해한 후, 50% 에탄올 용액을 대조군으로 하여 517 nm에서 DPPH용액의 흡광도를 약 1.0이 되도록 희석하여 사용하였다.DPPH (1,1-diphenyl-2-picrylhydrazyl, sigma) radical scavenging activity was measured using the Blois method. After dissolving 0.15 mM DPPH in 100 mL of absolute ethanol, a 50% ethanol solution was used as a control, and the absorbance of the DPPH solution at 517 nm was diluted to about 1.0.
상기 방법으로 제조된 단삼 및 홍삼 복합추출물과 단삼 및 홍삼 생물전환 복합추출물을 각각 100배 희석하여 시료로 만들었다. 각 시료 0.5 mL에 DPPH 용액 5 mL을 혼합하여 정확히 3분 동안 반응시키고 UV-1601(UV-visible spectrophotometer)를 이용하여 517 nm에서 흡광도를 측정한 후 하기 수학식 1을 통하여 RSA(radical scavenging activity, %)로 나타내었다.The sweet ginseng and red ginseng complex extracts and the sweet ginseng and red ginseng bioconversion complex extracts prepared by the above method were diluted 100 times to prepare samples. 5 mL of DPPH solution was mixed with 0.5 mL of each sample, reacted for exactly 3 minutes, and absorbance was measured at 517 nm using UV-1601 (UV-visible spectrophotometer), and then RSA (radical scavenging activity, %).
<수학식 1><Equation 1>
DPPH radical scavenging activity (%)=(1-As/Ac)×100DPPH radical scavenging activity (%)=(1-As/Ac)×100
(여기서 As: Absorbance of group with sample, Ac: Absorbance of group without sample이다.)(Here, As: Absorbance of group with sample, Ac: Absorbance of group without sample.)
도 7 및 표 4에서 확인할 수 있듯이, 단삼 및 홍삼 복합추출물의 DPPH 라디칼 소거능 결과는 5:5, 6:4(단삼:홍삼)의 중량비에서 최대 약 80%의 전자 공여능을 보였으며, 다른 혼합비율에서도 개별 추출물보다 높은 활성을 보이고 있다. 또한 단삼 및 홍삼 생물전환 복합추출물의 경우에도 마찬가지로 5:5, 6:4 비율에서 가장 높은 라디컬 소거 능력을 보였으며, 단삼 및 홍삼 복합추출물에 비해 작게는 20%에서 높게는 35% 가량의 소거 능력의 차이를 보였다.As can be seen in Figure 7 and Table 4, DPPH radical scavenging activity results of the complex extract of sweet ginseng and red ginseng showed an electron donating ability of up to about 80% at a weight ratio of 5:5, 6:4 (dansam: red ginseng), and different mixing ratios Also shows higher activity than individual extracts. Also, in the case of bioconversion complex extracts of sweet ginseng and red ginseng, similarly, it showed the highest radical scavenging ability at the ratio of 5:5 and 6:4. There was a difference in ability.
DPPH 라디칼 소거능 (%)Complex extract
DPPH radical scavenging activity (%)
이는 단삼 및 홍삼의 DPPH 라디컬 소거능에 관한 여러 연구와도 일치하는 부분이고, 생물전환 공정이 포함되는 것이 소거능을 상당 부분 향상시킨다고 볼 수 있으며, 특히 적절한 중량비로 적용함에 따라 상승효과를 유도할 수 있다.This is consistent with several studies on the DPPH radical scavenging activity of single ginseng and red ginseng, and it can be seen that the inclusion of a bioconversion process significantly improves the scavenging ability. have.
실시예 7: 단삼 및 홍삼 생물전환 복합추출물의 ABTs radical 소거능 측정Example 7: Measurement of ABTs radical scavenging ability of bioconversion complex extracts of sweet and red ginseng
ABTS 라디칼 소거능은 Pellegrini N 등(1999)의 방법에 따라 측정하였다. 상기 실시예 6과 같은 방법으로 제조한 시료 100 uL에 0.1 M 포스페이트 버퍼(phosphate buffer, pH 5.0) 100 uL와 10 mM 과산화수소(hydrogen peroxide) 20 uL를 가하고 37℃에서 5분 동안 예비반응 시켰다. ABTS radical scavenging ability was measured according to the method of Pellegrini N et al. (1999). To 100 uL of the sample prepared in the same manner as in Example 6, 100 uL of 0.1 M phosphate buffer (pH 5.0) and 20 uL of 10 mM hydrogen peroxide were added and pre-reacted at 37°C for 5 minutes.
반응물에 1.25 mM의 ABTS와 과산화효소(peroxidase, 1 U/mL)를 각각 30 uL씩 넣은 후 다시 37℃에서 10분 동안 반응시켰다. 반응물은 405 nm의 멀티플레이트 리더(Multiplate Reader. Sunrise RC/TS/TS Color-TC/TW/BC/6Filter, Tecan Austria GmbH, Grφdig, Austria)를 이용하여 흡광도를 측정하였고 하기 수학식 2에 의해 소거능을 계산하였다. 무처리구의 경우에는 시료 대신 DMSO를 사용하였다.30 uL each of 1.25 mM ABTS and peroxidase (1 U/mL) were added to the reaction mixture, and then reacted again at 37°C for 10 minutes. The reactant was measured for absorbance using a 405 nm multi-plate reader (Multiplate Reader. Sunrise RC/TS/TS Color-TC/TW/BC/6Filter, Tecan Austria GmbH, Grφdig, Austria), and scavenging ability according to Equation 2 below. Was calculated. In the case of the untreated group, DMSO was used instead of the sample.
<수학식 2><Equation 2>
ABTS radical scavenging activity (%)=(1-As/Ac)×100ABTS radical scavenging activity (%)=(1-As/Ac)×100
(여기서 As: Absorbance of group with sample, Ac: Absorbance of group without sample이다.)(Here, As: Absorbance of group with sample, Ac: Absorbance of group without sample.)
도 8 및 표 5에서 확인할 수 있듯이, ABTS 소거능 측정 결과는 실시예 6의 DPPH 소거능과 거의 유사하게 도출되었다.As can be seen in Figure 8 and Table 5, ABTS scavenging ability measurement results were derived almost similar to the DPPH scavenging ability of Example 6.
먼저 단삼 및 홍삼 효소반응물의 경우 모든 경우의 시료에서 60% 이상의 소거능을 보여주었고, 특히 4:6 비율에서 가장 높게 나타났고, 단삼 또는 홍삼 단일 효소반응물(0:10 또는 10:0)에 비해 약 20% 정도 소거능이 높은 결과를 보여준다. 그런데 단삼 및 홍삼 생물전환 복합추출물의 경우 전반적으로 모두 80% 이상의 높은 소거능을 보였으며, 생물전환공정이 앞선 결과와 마찬가지로 4:6의 중량비에서 최고의 소거능을 보였다. 실시예 6 및 실시예 7을 통하여 추측해 볼 때, 생물전환 공정이 수행됨으로써 항산화효과가 극대화된다는 것을 짐작할 수 있었다.First, the enzyme reactants of sweet ginseng and red ginseng showed more than 60% scavenging ability in all samples, especially 4:6. It was the highest in the ratio, and showed a result of about 20% higher scavenging ability than a single enzyme reactant (0:10 or 10:0) of single ginseng or red ginseng. However, in the case of bioconversion complex extracts of sweet and red ginseng, both showed high scavenging activity of 80% or more overall, and the bioconversion process showed the best scavenging activity at a weight ratio of 4:6, as in the previous results. When inferred through Examples 6 and 7, it was possible to guess that the antioxidant effect was maximized by performing the bioconversion process.
실시예 8: 단삼 및 홍삼 생물전환 복합추출물의 LDL 산화 억제 활성 측정Example 8: Measurement of LDL oxidation inhibitory activity of bioconversion complex extracts of sweet ginseng and red ginseng
LDL 산화 억제 활성 측정 실험은 LDL(1 mg/ml final conc.)과 상기 과정을 통하여 얻은 복합 단삼 및 홍삼 생물전환 복합추출물을 각기 종류별로 50배 희석하고(final conc.) 혼합하여 교반한 후 황산제이구리(CuSO4 10 uM)를 첨가한 후 다시 37℃에서 90분 동안 반응시켰다. 반응물의 흡광도는 234 nm의 멀티플레이트 리더를 이용하여 측정하였고 대조군인 프로부콜(probucol)의 값과 비교하여 상대적인 값으로 나타내었다.LDL oxidation inhibitory activity measurement experiment was conducted by diluting LDL (1 mg/ml final conc.) and the bioconversion complex extract obtained through the above process by 50 times for each type (final conc.), mixing, stirring, and sulfuric acid. After adding cupric (CuSO 4 10 uM), it was reacted again at 37°C for 90 minutes. The absorbance of the reactant was measured using a 234 nm multi-plate reader and expressed as a relative value compared with the value of the control, probucol.
도 9 및 표 6에서 확인할 수 있듯이, 단삼 또는 홍삼 단일 효소반응물이 약 30%의 억제능을 보였으며, 다른 모든 실험군에서는 60%를 상회하는 억제 활성을 보였다.As can be seen in Fig. 9 and Table 6, the single enzyme reaction of single ginseng or red ginseng showed an inhibitory activity of about 30%, and all other experimental groups showed inhibitory activity exceeding 60%.
특히 중량비가 4:6에 해당하는 실험군에서는 프로부콜과 거의 동일한 억제 활성을 보였다. 이는 앞서 나타난 항산화능 측정과도 유사한 결과이며, 동맥경화에 있어서 약리활성의 발휘를 기대해 볼 수 있다.In particular, the experimental group corresponding to the weight ratio of 4:6 showed almost the same inhibitory activity as probucol. This is a result similar to the measurement of antioxidant activity previously shown, and it can be expected to exhibit pharmacological activity in arteriosclerosis.
실시예 9: 단삼 및 홍삼 생물전환 복합추출물의 ox-LDL 유입 억제 활성 측정Example 9: Measurement of ox-LDL influx inhibitory activity of bioconversion complex extracts of sweet ginseng and red ginseng
24웰 플레이트에 웰 당 20,000 개의 내피세포를 분주한 다음 CO2 인큐베이터에서 24시간 동안 배양한 후, 형광물질이 표지된 LDL을 사용하여, 실시예 8에서와 같은 방법으로 반응물을 제조하였다. 상기 반응물은 24웰에 각각 100 ul씩 첨가하여 3시간 동안 추가로 배양하였고, 형광현미경을 이용하여 사진을 분석하였다.After dispensing 20,000 endothelial cells per well in a 24-well plate, incubating for 24 hours in a CO 2 incubator, a reactant was prepared in the same manner as in Example 8 using LDL labeled with a fluorescent substance. The reactants were added to each of 24 wells by 100 ul and incubated for an additional 3 hours, and the photographs were analyzed using a fluorescence microscope.
도 10에서 확인할 수 있듯이, 대조군에서는 상당량의 LDL이 내피세포 안으로 유입된데 비하여, 단삼:홍삼의 중량비를 4:6, 5:5 및 6:4로 한 시료에서는 LDL이 거의 세포내로 유입되지 않은 것으로 확인할 수 있었다.As can be seen in FIG. 10, in the control group, a significant amount of LDL was introduced into the endothelial cells, whereas in the sample in which the weight ratio of Dansam: red ginseng was 4:6, 5:5 and 6:4, LDL was hardly introduced into the cells. It could be confirmed.
실시예 10: 단삼 및 홍삼 생물전환 복합추출물 복용 시 혈압 변화의 확인Example 10: Confirmation of changes in blood pressure when taking a bioconversion complex extract of sweet ginseng and red ginseng
고혈압 환자 총 30명을 여섯 그룹으로 나누어 각 그룹에 상기 방법으로 제조된 단삼 추출물, 홍삼 추출물, 단삼 및 홍삼 복합추출물(단삼:홍삼=4:6), 단삼 생물전환 추출물(단삼:홍삼=10:0), 홍삼 생물전환 추출물(단삼:홍삼=0:10), 단삼 및 홍삼 생물전환 복합추출물(단삼:홍삼=4:6)을 20일 동안 매일 1.5 g씩 복용시키면서 혈압의 변화를 관찰하고 투여 전과 투여 후 매일 같은 시간에 측정한 수축기 혈압, 이완기 혈압 및 맥박을 측정하였다. 이때 각 실험군에서 가장 큰 차이를 보이거나 가장 작은 차이를 보이는 두가지 경우는 배제하여, 각 실험군에서 3명의 데이터를 명시하였다.A total of 30 hypertensive patients were divided into six groups, and each group was divided into a single ginseng extract, a red ginseng extract, a single ginseng and a red ginseng complex extract (danseng: red ginseng = 4:6), a single ginseng bioconversion extract (danseng: red ginseng = 10: 0), red ginseng bioconversion extract (danseng: red ginseng = 0:10), sweet ginseng and red ginseng bioconversion complex extract (danseng: red ginseng = 4:6), taking 1.5 g daily for 20 days to observe and administer changes in blood pressure Systolic blood pressure, diastolic blood pressure, and pulse rate were measured before and after administration at the same time every day. At this time, the two cases showing the largest difference or the smallest difference in each experimental group were excluded, and the data of three persons in each experimental group were specified.
도 11 내지 13에서 확인할 수 있듯이, 투여 직후부터 완만한 혈압 강하에 따른 혈압 조절효과가 관찰되었으며, 모든 환자에서 혈압강하 효과가 관찰되었고, 적정혈압 이하로는 강하되지 않았으므로 혈압조절에도 유효한 것으로 판단하였다.As can be seen in FIGS. 11 to 13, the blood pressure control effect according to the gentle drop in blood pressure was observed immediately after administration, and the blood pressure lowering effect was observed in all patients, and it was determined to be effective for blood pressure control as it did not drop below the appropriate blood pressure. I did.
도 11에서 확인할 수 있는 단삼 추출물, 및 단삼 생물전환 추출물의 차이 및 도 12에서 확인할 수 있는 홍삼 추출물, 및 홍삼 생물전환 추출물의 차이는 거의 없거나 아주 작은 차이로 나타나는 것에 비해, 도 13에서 확인할 수 있는 단삼 및 홍삼 복합추출물, 및 단삼 및 홍삼 생물전환 복합추출물의 경우 복용 전후 혈압 강하 차이가 크게 나타나며, 특히 생물전환 복합추출물의 경우에서 확연한 혈압강하 효과를 확인할 수 있다.The difference between the Dansam extract and Dansam bioconversion extract that can be found in FIG. 11, and the difference between the red ginseng extract and the red ginseng bio-conversion extract that can be confirmed in FIG. In the case of sweet ginseng and red ginseng complex extract, and sweet ginseng and red ginseng bioconversion complex extract, there is a large difference in blood pressure lowering before and after administration, and in particular, it can be confirmed that the blood pressure lowering effect is evident in the case of bioconversion complex extract.
Claims (16)
상기 단삼 생물전환 추출물 및 홍삼 생물전환 추출물은 단삼 추출물 및 홍삼 추출물에 양조 효소를 첨가한 후 제조되는 단삼 효소반응물 및 홍삼 효소반응물에 트리코데르마 레에세이(Trichoderma reesei) 배양액을 첨가하여 제조된 것이고,
상기 심혈관계 질환은 고혈압, 혈액순환장애 및 동맥경화로 이루어진 군으로부터 선택되는 것인 약학 조성물.
As a pharmaceutical composition for preventing or treating cardiovascular diseases comprising a Salvia miltiorrhiza bioconversion extract and a red ginseng bioconversion extract,
The single ginseng bioconversion extract and red ginseng bioconversion extract are prepared by adding a culture solution of Trichoderma reesei to a single ginseng enzyme reaction product and a red ginseng enzyme reaction product prepared after adding a brewing enzyme to the single ginseng extract and the red ginseng extract,
The cardiovascular disease is a pharmaceutical composition selected from the group consisting of hypertension, blood circulation disorder and arteriosclerosis.
단삼 추출물 및 홍삼 추출물에 양조 효소를 첨가하여 단삼 효소반응물 및 홍삼 효소반응물을 제조하는 효소처리 단계; 및
상기 단삼 효소반응물 및 홍삼 효소반응물에 트리코데르마 레에세이(Trichoderma reesei) 배양액을 반응시켜 단삼 생물전환 추출물 및 홍삼 생물전환 추출물을 제조하는 생물전환 단계.A method for preparing a pharmaceutical composition for preventing or treating cardiovascular diseases, comprising the following steps: Salvia miltiorrhiza bioconversion extract and red ginseng bioconversion extract, wherein the cardiovascular disease is hypertension, blood circulation disorder And the manufacturing method selected from the group consisting of atherosclerosis:
Enzymatic treatment step of preparing a sweet ginseng enzyme reaction product and a red ginseng enzyme reaction product by adding a brewing enzyme to the sweet ginseng extract and the red ginseng extract; And
A bioconversion step of reacting a culture solution of Trichoderma reesei with the enzyme reaction product of Danseng and the enzyme reaction of red ginseng to prepare a bioconversion extract of Dansam and a bioconversion extract of red ginseng.
상기 단삼 생물전환 추출물 및 홍삼 생물전환 추출물은 단삼 추출물 및 홍삼 추출물에 양조 효소를 첨가한 후 제조되는 단삼 효소반응물 및 홍삼 효소반응물에 트리코데르마 레에세이(Trichoderma reesei) 배양액을 첨가하여 제조된 것이고,
상기 심혈관계 질환은 고혈압, 혈액순환장애 및 동맥경화로 이루어진 군으로부터 선택되는 것인 식품 조성물.
As a food composition for improving cardiovascular diseases comprising a Salvia miltiorrhiza bioconversion extract and a red ginseng bioconversion extract,
The single ginseng bioconversion extract and red ginseng bioconversion extract are prepared by adding a culture solution of Trichoderma reesei to a single ginseng enzyme reaction product and a red ginseng enzyme reaction product prepared after adding a brewing enzyme to the single ginseng extract and the red ginseng extract,
The cardiovascular disease is a food composition selected from the group consisting of hypertension, blood circulation disorder and arteriosclerosis.
단삼 추출물 및 홍삼 추출물에 양조 효소를 첨가하여 단삼 효소반응물 및 홍삼 효소반응물을 제조하는 효소처리 단계; 및
상기 단삼 효소반응물 및 홍삼 효소반응물에 트리코데르마 레에세이(Trichoderma reesei) 배양액을 반응시켜 단삼 생물전환 추출물 및 홍삼 생물전환 추출물을 제조하는 생물전환 단계. Salvia miltiorrhiza ( Salvia miltiorrhiza ) biotransformation extract and red ginseng (red ginseng) a method of manufacturing food for improving cardiovascular disease including bioconversion extract, wherein the cardiovascular disease is hypertension, blood circulation disorder and arteriosclerosis The manufacturing method that is selected from the group consisting of:
Enzymatic treatment step of preparing a sweet ginseng enzyme reaction product and a red ginseng enzyme reaction product by adding a brewing enzyme to the sweet ginseng extract and the red ginseng extract; And
A bioconversion step of reacting a culture solution of Trichoderma reesei with the enzyme reaction product of Danseng and the enzyme reaction of red ginseng to prepare a bioconversion extract of Dansam and a bioconversion extract of red ginseng.
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