KR101975018B1 - Composition for lowering cholesterol comprising a mixture culture of Ginseng Berry-Auricularia auricula mycelia - Google Patents
Composition for lowering cholesterol comprising a mixture culture of Ginseng Berry-Auricularia auricula mycelia Download PDFInfo
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- KR101975018B1 KR101975018B1 KR1020170086335A KR20170086335A KR101975018B1 KR 101975018 B1 KR101975018 B1 KR 101975018B1 KR 1020170086335 A KR1020170086335 A KR 1020170086335A KR 20170086335 A KR20170086335 A KR 20170086335A KR 101975018 B1 KR101975018 B1 KR 101975018B1
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- ginseng fruit
- ginseng
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
본 발명은 인삼열매-목이버섯 균사체 혼합 배양물로 이루어지거나 이를 유효성분으로 포함하는 콜레스테롤 저하용 조성물을 제공한다. 본 발명에 따른 인삼열매-목이버섯 균사체 혼합 배양물은 인삼열매의 처리 및 혼합 배양 과정에 의해 희귀 진세노사이드의 함량이 증가하고 목이버섯 균사체 고유의 생리활성 성분을 동시에 포함하기 때문에 우수한 콜레스테롤 저하 효능을 갖는다. 따라서, 본 발명에 따른 인삼열매-목이버섯 균사체 혼합 배양물은 비만, 지방간, 제2형 당뇨, 고중성지방혈증, 고콜레스테롤혈증, 고지혈증, 이상지질혈증, 동맥경화증 또는 상기 질환들 중 적어도 2개 이상이 동시다발적으로 발생하는 대사증후군 등을 예방, 개선 또는 치료하는데에 유용한 기능성 식의약 소재로 사용될 수 있다.The present invention provides a composition for lowering cholesterol comprising or consisting of a mixed culture of a ginseng fruit-thistle mushroom mycelium. The mixed culture of ginseng fruit-thistle mushroom mycelium according to the present invention increases the content of rare ginsenoside by the treatment of the ginseng fruit and the mixed culture process, and simultaneously contains the physiologically active ingredient peculiar to the thistle mushroom mycelium, Respectively. Therefore, the mixed culture of ginseng fruit-thistle mushroom mycelium according to the present invention can be used for the treatment of obesity, fatty liver, type 2 diabetes, hypertriglyceridemia, hypercholesterolemia, hyperlipidemia, dyslipidemia, arteriosclerosis, Or more can be used as a functional food material useful for preventing, improving or treating metabolic syndrome which occurs simultaneously.
Description
본 발명은 콜레스테롤 저하용 조성물에 관한 것으로서, 본 발명의 조성물은 인삼열매 유래 기질과 목이버섯 균사체의 혼합 배양에 의해 얻은 산물로 이루어지거나 이를 유효성분으로 포함하는 것을 특징으로 한다.The present invention relates to a composition for lowering cholesterol, and the composition of the present invention is characterized by comprising a product obtained by mixed cultivation of a ginseng fruit-derived substrate and a mycelium of mycelium, or as an effective ingredient.
인삼(Panax ginseng C.A. Meyer)은 한반도가 원산인 우리나라의 특유의 약용식물로 2,000여년 전부터 널리 사용되어 왔다. 인삼의 반복적인 습열 처리와 건조를 거쳐 제조한 홍삼은 약효가 뛰어난 미량 진세노사이드가 새롭게 생성되어 인삼과는 다른 활성을 나타낸다. 인삼의 생리 활성에 대한 연구로부터 인삼의 여러 약리적 효과들은 주로 그 핵심성분인 인삼 특유의 사포닌, 즉 진세노사이드(ginsenoside) 때문인 것으로 알려져 있다. 진세노사이드는 탄소 수가 30개인 triterpene 골격에 글루코스, 아라비노스, 람노스 등 당이 붙어 있는 배당체 구조이며 그 골격에 따라 protopanaxadiol(PPD) 계열과 protopanaxatriol(PPT) 계열로 구분된다. 다른 배당체들과 마찬가지로 인삼 배당체인 진세노사이드는 섭취 후 소화과정에서 장관에 존재하는 미생물이 보유한 분해효소에 의해 당을 제거하는 탈당과정을 거쳐야 체내 흡수가 용이하다. 식약처 조사 결과 한국인의 상당수는 장관에 당 분해효소의 활성이 없거나 매우 약하여 인삼의 효능을 제대로 제공받지 못하는 것으로 보고되었다.Ginseng (Panax ginseng C.A. Meyer) is a Korean medicinal herb that is native to the Korean peninsula and has been widely used for over 2,000 years. Red ginseng, which has been produced by repeated heat treatment and drying of ginseng, has a new activity of ginsenoside which is different from ginseng. From the studies on the physiological activity of ginseng, various pharmacological effects of ginseng are known to be mainly due to saponin, ginsenoside, which is a key ingredient of ginseng. Ginsenoside is a glycoside structure with a sugar number of 30 in the triterpene skeleton, such as glucose, arabinose and rhamnose. Depending on its structure, it is divided into protopanaxadiol (PPD) and protopanaxatriol (PPT). Like other glycosides, ginsenoside, which is a ginseng glycoside, is easily absorbed through the process of elimination of sugar by the degrading enzyme of microorganisms present in the digestive tract during ingestion. A large number of Koreans have reported that the enzymes in the intestinal tract have no activity or are so weak that they do not receive the efficacy of ginseng.
따라서 개인 간의 진세노사이드 흡수율 및 효능의 차이를 최소화시키고 진세노사이드의 효과를 극대화시키기 위해서는 고분자 배당체를 섭취 전에 저분자화 시켜 체내 흡수율을 높이는 것이 바람직하며 이에 대한 연구가 다양하게 이루어지고 있다. 예를 들면, 최근 열 처리, 산/염기 처리 등의 물리적 화학적 처리법보다는, 반응에 따른 다양한 전환이 가능하고 특정 저분자 배당체를 선택적으로 생산할 수 있는 미생물이나 효소를 이용한 생물학적 처리방법에 관한 연구가 활발하게 이루어지고 있다. 지금까지 이들 진세노사이드를 연구하는데는 주로 인삼의 지하부인 뿌리를 이용하여 왔다. 그러나 최근 연구를 통해 인삼 지하부인 인삼근 외에도 인삼 엽 및 인삼열매 등 지상부에도 진세노사이드의 함량이 높은 것으로 알려졌다(Attele AS et al, Biochem Pharmacol, 58; 1685-1693, 1999). 인삼은 대개 4~6년근을 수확하여 건삼, 홍삼 및 이를 이용한 각종 제품들로 상품화되며, 그 과정에서의 인삼의 잎과 열매는 폐기물로 취급되어 왔다.Therefore, in order to maximize the effect of ginsenoside, it is desirable to increase the absorption rate of the ginsenoside by low molecular weight before ingestion of the ginsenoside. For example, recent research on biological treatment methods using microorganisms or enzymes capable of various conversions according to the reaction and selectively producing specific low molecular weight glycosides, rather than physical and chemical treatment methods such as heat treatment and acid / base treatment . Until now, studies on these ginsenosides have mainly used roots of ginseng underground. However, recent research has shown that ginsenosides are also found in the upper parts of ginseng leaves and ginseng fruits in addition to the ginseng undergrowths of ginseng (Attele AS et al, Biochem Pharmacol, 58, 1685-1693, 1999). Ginseng is usually harvested for 4-6 years, and it is commercialized as ginseng, red ginseng and various products using it. In the process, ginseng leaves and fruits have been treated as waste.
인삼열매는 조 사포닌 함량이 중량 g 당 240㎎ 이상으로 6년근 인삼의 중량 g당 80㎎에 비해 3배 정도 높아 사포닌 생산에 좋은 자원으로 평가된다. 그러나 인삼 재배농가에서는 6년근 재배 시 인삼근의 성장을 촉진하고 종자를 확보하기 위해 4년생 때 종자를 수확하고 3년생, 5년생, 6년생 때는 종자를 받지 않고 꽃대뿐 아니라 줄기부터 원천적으로 모두 제거하여 연간 3천여 톤의 열매가 버려지고 있다. 인삼근의 진세노사이드는 재배토양과 기후조건에 따라 성분을 달리하는 반면 인삼열매의 경우 조성과 함량 차이가 적은 것으로 알려져 있다. 인삼열매는 높은 사포닌 함량으로 인해 최근 음료 등으로 개발되고 있고 인삼열매 추출물은 남성 성기능 개선(대한민국 등록특허 제10-1241050호), 파킨슨병/알츠하이머 예방 및 치료(대한민국 등록특허 제10-1581497호), 제2형 당뇨병 치료(대한민국 등록특허 제10-1484502호)와 관련된 여러 활성을 가지는 것으로 보고되고 있다. 최근 인삼열매로부터 활성 효과가 뛰어난 사포닌을 회수하는 방법이 연구되고 있다. 예를 들어, 대한민국 등록특허 제10-1330935호에는 인삼열매로부터 과육을 탈피하여 인삼과육액을 제조하는 단계; 상기 인삼과육액을 초음파에 30분 내지 2시간 동안 방치하여 인삼열매 과육 성분을 용출시킨 후 원심분리하는 단계; 상기 원심분리된 상층액을 여과하는 단계; 및 상기 여과액을 분자량 1000 내지 2000 크기로 한외여과하여 물, 이온성 물질 및 수용성 저분자 물질을 제거하고 15 내지 30%로 농축액을 수득하는 단계를 포함하는 것을 특징으로 하는 진세노사이드 Re가 강화된 인삼열매 추출물의 제조방법이 개시되어 있다. 또한, 대한민국 등록특허공보 제10-1416669호에는 1 중량부의 인삼 열매를 5~300 중량부의 증류수에 넣고, 35분~45분 범위 내의 시간 동안 90℃~110℃ 범위 내의 온도에서 초음파 처리하는 단계; 및 상기 초음파 처리한 인삼 열매를 감압하에 농축시키고 동결 건조하는 단계;를 포함하여, 진세노사이드 Rg2, Rg3, Rh1, Rk1 및 F4의 함량을 증가시키는 것을 특징으로 하는 인삼 열매 제제의 제조방법이 개시되어 있다. 또한, 대한민국 등록특허 제10-1051519호에는 인삼열매를 증숙한 후 인삼열매의 수분함량이 12±3%가 되도록 건조하여 분쇄하는 단계와; 상기 분쇄된 인삼열매 분말을 수용성 용매 또는 수용성 용매와 유기 용매가 혼합된 용매에 용해시켜 알파-갈락토시다제, 펙티나제, 셀룰라제, 락타제 중에서 선택된 1종 또는 2종 이상과 효소 반응시키는 단계와; 상기 효소반응된 조성물에 EM(Effective Micro-organisms) 발효함초액을 혼합하여 추출하는 단계를 포함함을 특징으로 인삼열매 추출물의 제조방법이 개시되어 있다. 또한, 대한민국 등록특허 제10-1182741호에는 Aspergillus niger KCCM 11239 균주 유래의 분자량 123 kDa 이며 최적 온도안정성 70℃, 최적 PH 안정성 4.0인 β-glucosidase 효소를 이용함을 특징으로 하는 인삼 사포닌 성분 ginsenoside Rb1 을 Rd, F2 및 Rg3으로 생물전환하는 방법이 개시되어 있다. 또한, 대한민국 등록특허 제10-0443411호에는 페니실리움 속 또는 유박테리움 속 유래 베타글리코시다제(β-glycosidase)를 이용하여 진세노사이드 Re 또는 진세노사이드 Rg1으로부터 진세노사이드 F1을 제조하는 방법이 개시되어 있다.Ginseng fruit is more than 240 mg per gram of crude saponin, which is three times higher than 80 mg per g of 6-year-old ginseng, which is a good resource for saponin production. However, in ginseng cultivator, seeds were harvested at the age of 4 years to promote the growth of ginseng roots at the time of cultivation for 6 years, and at the end of 3, 5, and 6 years, 3,000 tons of fruit are being abandoned annually. Ginsenoside of ginseng root is different according to cultivation soil and climatic conditions, while ginseng fruit is known to have little difference in composition and content. The ginseng fruit has recently been developed as a beverage due to its high saponin content. The ginseng fruit extract has been shown to improve male sexual function (Korean Patent No. 10-1241050), Parkinson's disease / Alzheimer's disease prevention and treatment (Korean Patent No. 10-1581497) , And
최근 소득수준이 높아짐에 따라 식생활 문화에 있어서 고칼로리 식품의 섭취가 늘어 비만 및 각종 성인질환 발병율이 높아지고 있다. 성인성 질환을 유발시키는 요인 중에서도 가장 주된 요인은 동물성 지방의 과다한 섭취로 인한 혈중 고콜레스테롤로서 고지혈증, 동맥경화증, 지질 관련 대사증후군과 같은 질환의 위험 지표가 된다. 콜레스테롤 저하 효능을 갖는 기능성 소재로는 홍국, 버섯 균사체 등이 있다. 홍국(red yeast rice, red koji)은 붉은색의 사상균인 모나스커스(Monascus)속의 균을 곡류에 접종하여 제조한 것으로서, 홍국균이 생성하는 2차 대사산물인 메비놀린[혹은 로바스타틴(lovastatin), 모나콜린(monacolin) K, 또는 메바코르(mevacor)로 표시됨]이 콜레스테롤 생합성효소인 HMG-CoA(3-hydroxy-methyl-3- glutaryl-coenzyme) 환원효소를 강력하게 저해하여 혈중지질 농도를 감소시키고 콜레스테롤 합성을 억제한다는 등의 각종 기능성이 보고되고 있으며(Wang IK et al., J. Agri. Food Chem. 48: 3183-3189 2000; Endo A. et al., J. Antibiotechnol. 38: 420-422 1985; Manzoni M & Rollini M. App. Microbiol. Biotechnol. 58: 555-564 2002; Wei W. et al., J. Nutri. Biochem. 14: 314-318 2003), 이로 인해 홍국균이 크게 주목을 받고 있다. 또한, 목이버섯은 식약처에 의해 장 건강을 개선하는 효능이 인정된 소재로서 그 외에도 항당뇨, 항산화, 콜레스테롤 저하 효능을 갖는 것으로 알려져 있다.As the recent income level increases, the intake of high-calorie foods increases in the dietary culture, and the incidence of obesity and various adult diseases is increasing. Among the factors causing adult diseases, the most important factor is hyperlipidemia of blood due to excessive intake of animal fat, which is a risk index for diseases such as hyperlipidemia, arteriosclerosis and lipid-related metabolic syndrome. Functional materials having cholesterol lowering effect include red yeast and mushroom mycelium. Red yeast rice (red koji) is a red yeast rice produced by inoculating a grain of the genus Monascus, which is a red mold, into the cereals. It is produced by the second metabolite produced by Hong Kook-gum, mebynolin (lovastatin, Monacolin K or mevacor] strongly inhibits HMG-CoA (3-hydroxy-methyl-3-glutaryl-coenzyme) reductase, which is a cholesterol biosynthesis enzyme, (Wang IK et al., J. Agri. Food Chem. 48: 3183-3189 2000; Endo A. et al., J. Antibiotechnol. 38: 420-422 1985 Manzoni M & Rollini M. App. Microbiol. Biotechnol. 58: 555-564 2002; Wei W. et al., J. Nutri. Biochem. 14: 314-318 2003) . In addition, throat mushroom is a substance recognized as improving the intestinal health by a pharmacopeia, and it is known that it has anti-diabetic, antioxidant and cholesterol-lowering effects.
본 발명은 종래의 기술적 배경하에서 도출된 것으로서, 본 발명의 목적은 인삼열매 유래 기질을 기반으로 콜레스테롤 저하용 조성물을 제공하는데에 있다.The present invention has been made under the background of the prior art, and an object of the present invention is to provide a composition for lowering cholesterol based on a ginseng fruit-derived substrate.
본 발명자들은 인삼열매가 희귀 진세노사이드를 생산하는데 필요한 유효 기질인 진세노사이드 Rd와 Rd 등을 충분히 보유하고 있다는 점, 인삼열매를 증숙 가공에 의해 전처리하고 인삼열매에 존재하는 진세노사이드를 특정 효소 단독 또는 특정 효소들의 조합으로 처리하면 다양한 희귀 진세노사이드를 높은 함량으로 생산할 수 있다는 점을 확인하였다. 또한, 본 발명자들은 인삼열매 유래 기질을 홍국 또는 목이버섯 균사체와 혼합 배양하여 얻은 산물이 우수한 콜레스테롤 저하 효능을 가지며 다양한 생리활성 성분을 포함하고 있기 때문에 의약품 소재 또는 건강기능식품 소재로서의 활용 가치가 매우 크다는 점을 확인하고 본 발명을 완성하였다.The present inventors have found that ginseng fruit has a sufficient amount of ginsenosides Rd and Rd, which are effective substrates for producing rare ginsenoside, that the ginseng fruit is pretreated by steam milling and the ginsenoside present in ginseng fruit is identified It has been confirmed that the treatment with a single enzyme or a combination of specific enzymes can produce a variety of rare ginsenosides in high content. Further, the inventors of the present invention found that the product obtained by mixing the substrate derived from ginseng fruit with the mycelia of Hong jung or throat mushroom has an excellent cholesterol-lowering effect and contains various physiologically active ingredients, so that it is very useful value as a medicine material or health functional food material And the present invention has been completed.
상기 목적을 해결하기 위하여 본 발명은 인삼열매-목이버섯 균사체 혼합 배양물로 이루어지거나 이를 유효성분으로 포함하는 콜레스테롤 저하용 조성물을 제공한다. 상기 인삼열매-목이버섯 균사체 혼합 배양물은 인삼열매 유래 기질을 목이버섯 균사체와 혼합하고 배양하여 얻은 산물이다. 또한, 상기 인삼열매 유래 기질은 인삼열매 착즙액, 인삼열매 추출액, 인삼열매 과육 착즙액 또는 인삼열매 과육 추출액에서 선택되거나 인삼열매 착즙액, 인삼열매 추출액, 인삼열매 과육 착즙액, 인삼열매 과육 추출액 또는 이들의 농축액과 효소와의 반응에 의해 얻은 산물에서 선택된다. 또한, 상기 효소는 베타-글루코시다아제(β-glucosidase), 헤미셀룰라아제(hemicellulase) 또는 이들의 혼합 효소에서 선택된다.In order to solve the above-mentioned problems, the present invention provides a composition for lowering cholesterol comprising a mixed culture of ginseng fruit-thistle mushroom mycelium or containing it as an active ingredient. The mixed culture of the ginseng fruit-thistle mushroom mycelium is a product obtained by mixing ginseng fruit-derived substrate with thymus mycelia and culturing. The ginseng fruit-derived substrate may be selected from ginseng fruit juice extract, ginseng fruit extract, ginseng fruit pulp extract or ginseng fruit pulp extract, or ginseng fruit juice extract, ginseng fruit extract, ginseng fruit pulp extract, ginseng fruit pulp extract or And the products obtained by the reaction of these concentrates with enzymes. In addition, the enzyme is selected from beta-glucosidase, hemicellulase, or a mixed enzyme thereof.
본 발명에 따른 인삼열매-목이버섯 균사체 혼합 배양물은 인삼열매의 처리 및 혼합 배양 과정에 의해 희귀 진세노사이드의 함량이 증가하고 목이버섯 균사체 고유의 생리활성 성분을 동시에 포함하기 때문에 우수한 콜레스테롤 저하 효능을 갖는다. 따라서, 본 발명에 따른 인삼열매-목이버섯 균사체 혼합 배양물은 비만, 지방간, 제2형 당뇨, 고중성지방혈증, 고콜레스테롤혈증, 고지혈증, 이상지질혈증, 동맥경화증 또는 상기 질환들 중 적어도 2개 이상이 동시다발적으로 발생하는 대사증후군 등을 예방, 개선 또는 치료하는데에 유용한 기능성 식의약 소재로 사용될 수 있다.The mixed culture of ginseng fruit-thistle mushroom mycelium according to the present invention increases the content of rare ginsenoside by the treatment of the ginseng fruit and the mixed culture process, and simultaneously contains the physiologically active ingredient peculiar to the thistle mushroom mycelium, Respectively. Therefore, the mixed culture of ginseng fruit-thistle mushroom mycelium according to the present invention can be used for the treatment of obesity, fatty liver,
도 1은 성숙 인삼열매 착즙 농축액을 정제 DT-BGL 및 정제 CS-BGL과 반응시켰을 때 반응 생성물 내 진세노사이드의 함량 변화를 나타낸 것이다.
도 2는 성숙 인삼열매를 상압(게이지 압력으로 환산하면 0 atm에 해당함; 절대압력 = 대기압(1 atm) + 게이지 압력) 및 다양한 온도 조건에서 스팀으로 15시간 증숙 가공하였을 때 인삼열매 착즙액의 사포닌 수율 변화를 나타낸 것이다.
도 3은 성숙 인삼열매를 다양한 압력 조건 및 60℃의 온도 조건에서 스팀으로 15시간 증숙 가공하였을 때 인삼열매 착즙액의 사포닌 수율 변화를 나타낸 것이다.Figure 1 shows the content of ginsenosides in the reaction product when the juice concentrate of matured ginseng fruit was reacted with purified DT-BGL and purified CS-BGL.
FIG. 2 is a graph showing the effect of the saponin content of ginseng fruit juice on the matured ginseng fruit when steamed for 15 hours under various pressures (atmospheric pressure (1 atm) + gauge pressure) at normal pressure (equivalent to 0 atm in terms of gauge pressure) Yield change.
FIG. 3 shows changes in saponin yield of ginseng fruit juice when matured ginseng was steamed for 15 hours under various pressure conditions and temperature conditions of 60 ° C.
이하, 본 발명에서 사용한 용어를 설명한다.Hereinafter, terms used in the present invention will be described.
본 발명에서 사용되는 용어인 "희귀 진세노사이드"는 인삼에 미량으로 존재하거나 별도의 물리적, 화학적 또는 생물학적 처리를 통해 새롭게 생성된 진세노사이드를 모두 포함하는 개념이다.As used herein, the term " rare ginsenoside " is a concept that includes all of ginsenosides that are present in trace amounts in ginseng or that are newly produced through separate physical, chemical, or biological treatments.
본 발명에서 사용되는 용어 "배양물"이란 미생물을 공지의 액체 배지 또는 고체 배지에서 배양시켜 수득한 산물을 의미하여, 미생물이 포함되는 개념이다.The term " culture product " used in the present invention means a product obtained by culturing a microorganism in a known liquid medium or solid medium, and includes a microorganism.
본 발명에서 사용되는 용어 "약학적으로 허용가능한" 및 "식품학적으로 허용가능한"이란 생물체를 상당히 자극하지 않고 투여 활성 물질의 생물학적 활성 및 특성을 저해하지 않는 것을 의미한다.As used herein, the terms " pharmaceutically acceptable " and " pharmaceutically acceptable " are intended to mean not significantly irritating the organism and not interfering with the biological activity and properties of the administered active substance.
본 발명에서 사용되는 용어 "예방"은 본 발명의 조성물의 투여로 특정 질환의 증상을 억제하거나 진행을 지연시키는 모든 행위를 의미한다.As used herein, the term " prophylactic " means any act that inhibits the symptoms of a particular disease or delays its progress by administration of the composition of the present invention.
본 발명에서 사용되는 용어 "치료"는 본 발명의 조성물의 투여로 특정 질환의 증상을 호전 또는 이롭게 변경시키는 모든 행위를 의미한다.The term " treatment " as used herein refers to any action that improves or alleviates the symptoms of a particular disease upon administration of the composition of the present invention.
본 발명에서 사용되는 용어 "개선"은 치료되는 상태와 관련된 파라미터, 예를 들면 증상의 정도를 적어도 감소 또는 완화시키는 모든 행위를 의미한다.As used herein, the term " improvement " means any action that at least diminishes or alleviates the parameters associated with the condition being treated, for example, the severity of the condition.
본 발명에서 사용되는 용어 "투여"는 임의의 적절한 방법으로 개체에 소정의 본 발명의 조성물을 제공하는 것을 의미한다. 이때, 개체는 본 발명의 조성물을 투여하여 특정 질환의 증상이 호전될 수 있는 질환을 가진 인간, 원숭이, 개, 염소, 돼지 또는 쥐 등 모든 동물을 의미한다.The term " administering " as used herein is meant to provide any desired composition of the invention to an individual by any suitable method. The term " individual " means any animal such as a human, a monkey, a dog, a goat, a pig, or a mouse having a disease in which symptoms of a specific disease can be improved by administering the composition of the present invention.
본 발명에서 사용되는 용어 "약학적으로 유효한 양"은 의학적 치료에 적용 가능한 합리적인 수혜 또는 위험 비율로 질환을 치료하기에 충분한 양을 의미하며, 이는 개체의 질환의 종류, 중증도, 약물의 활성, 약물에 대한 민감도, 투여 시간, 투여 경로 및 배출비율, 치료기간, 동시에 사용되는 약물을 포함한 요소 및 기타 의학 분야에 잘 알려진 요소에 따라 결정될 수 있다.The term " pharmaceutically effective amount " as used herein means an amount sufficient to treat a disease at a reasonable benefit or risk rate applicable to medical treatment, including the type of disease, severity, activity of the drug, The time of administration, the route and rate of excretion of the drug, the duration of the treatment, factors including drugs used simultaneously and other factors well known in the medical arts.
본 발명에서 사용되는 용어 "조성물"은 2가지 이상의 성분이 균일하게 혼합되어 있는 상태의 물질을 의미하며, 완제품뿐만 아니라 완제품 제조를 위한 중간 소재를 포함하는 개념이다.The term " composition " as used in the present invention means a material in which two or more components are uniformly mixed, and includes not only an article but also an intermediate material for producing an article.
이하, 본 발명을 구체적으로 설명한다.Hereinafter, the present invention will be described in detail.
본 발명은 인삼열매 유래 기질을 기반으로 하는 콜레스테롤 저하용 조성물에 관한 것이다. 본 발명의 일 예에 따른 콜레스테롤 저하용 조성물은 인삼열매-목이버섯 균사체 혼합 배양물로 이루어지거나 이를 유효성분으로 포함한다. 또한, 상기 인삼열매-목이버섯 균사체 혼합 배양물은 인삼열매 유래 기질을 목이버섯 균사체와 혼합하고 배양하여 얻은 산물이다.The present invention relates to a composition for lowering cholesterol based on a ginseng fruit-derived substrate. The composition for lowering cholesterol according to one embodiment of the present invention comprises or is contained as an active ingredient in a mixed culture of ginseng fruit-thistle mushroom mycelium. In addition, the mixed culture of the ginseng fruit-thistle mushroom mycelium is a product obtained by mixing ginseng fruit-derived substrate with thymus mycelia and culturing.
인삼열매 유래 기질Ginseng fruit-derived substrate
본 발명에서 인삼열매 유래 기질은 인삼열매로부터 얻은 진세노사이드 함유 기질을 의미한다. 상기 인삼열매 유래 기질은 인삼열매 착즙액, 인삼열매 추출액, 인삼열매 과육 착즙액 또는 인삼열매 과육 추출액에서 선택될 수 있다. 또한, 상기 인삼열매 유래 기질은 희귀 진세노사이드의 함량을 고려할 때 바람직하게는 인삼열매 착즙액, 인삼열매 추출액, 인삼열매 과육 착즙액, 인삼열매 과육 추출액 또는 이들의 농축액과 효소와의 반응에 의해 얻은 산물에서 선택될 수 있다. 상기 효소는 베타-글루코시다아제(β-glucosidase), 헤미셀룰라아제(hemicellulase) 또는 이들의 혼합 효소에서 선택될 수 있다.In the present invention, a substrate derived from ginseng fruit means a ginsenoside-containing substrate obtained from ginseng fruit. The ginseng fruit-derived substrate may be selected from ginseng fruit juice extract, ginseng fruit extract, ginseng fruit pulp juice extract or ginseng fruit pulp extract. In consideration of the content of rare ginsenoside, the ginseng fruit-derived substrate is preferably selected from the group consisting of ginseng fruit juice extract, ginseng fruit extract, ginseng fruit pulp juice extract, ginseng fruit pulp extract, Can be selected from the obtained products. The enzyme may be selected from beta-glucosidase, hemicellulase, or a mixed enzyme thereof.
상기 인삼열매의 공급원인 인삼은 품종, 원산지 등이 특별히 제한되지 않는다. 예를 들어 상기 인삼열매는 고려인삼의 청경, 연풍, 선풍, 청선, 천량, 고풍, 금풍, 선원, 선향 등과 같이 다양한 품종에서 선택되는 인삼의 열매를 사용할 수 있고 삼칠삼, 전칠삼, 미국삼, 중국삼, 베트남삼, 죽절삼 등과 같이 다양한 원산지에서 선택되는 인삼을 열매를 사용할 수도 있다.The ginseng as a source of the ginseng fruit is not particularly limited in terms of the variety, origin, and the like. For example, the ginseng fruit may be selected from various kinds of ginseng such as Korean ginseng, Korean ginseng, Korean ginseng, Chinese ginseng, American ginseng, Chinese ginseng, Chinese ginseng , Vietnamese samphire, and mandarin oranges can be used.
또한, 상기 인삼열매는 미성숙 열매 또는 성숙 열매에서 선택될 수 있으며, 인삼열매에 존재하는 진세노사이드의 조성비를 고려할 대 성숙 열매인 것이 바람직하다.In addition, the ginseng fruit may be selected from immature fruit or mature fruit, and it is preferable that the ginseng fruit is a mature fruit considering the composition ratio of ginsenoside present in the ginseng fruit.
또한, 상기 인삼열매는 다양한 희귀 진세노사이드의 생성 및 함량 증가를 고려할 때 바람직하게는 증숙 가공에 의해 전처리된 것이다. 상기 증숙 가공에 의한 인삼열매의 전처리는 인삼열매를 0.4~1 atm의 게이지 압력 및 50~70℃의 온도 조건에서 스팀으로 2~24 hr 동안 처리하는 것으로 구성되는 것이 바람직하고 사포닌 수율을 고려할 때 인삼열매를 0.5~1 atm의 게이지 압력 및 55~70℃의 온도 조건에서 스팀으로 10~20 hr 동안 처리하는 것으로 구성되는 것이 더 바람직하다.In addition, the ginseng fruit is preferably pretreated by the steaming process in consideration of the production of various rare ginsenosides and the increase of the content. The pretreatment of the ginseng fruit by the steaming process preferably comprises treating the fruit of ginseng with steam at a gauge pressure of 0.4 to 1 atm and a temperature of 50 to 70 ° C for 2 to 24 hours and considering the saponin yield, It is more preferable that the fruit is treated with steam at a gauge pressure of 0.5 to 1 atm and at a temperature of 55 to 70 DEG C for 10 to 20 hours.
또한, 상기 베타-글루코시다아제(β-glucosidase)는 인삼열매에 존재하는 진세노사이드의 희귀 진세노사이드로의 전환시 반응 효율 및 생성되는 희귀 진세노사이드의 생리 활성과 다양성 등을 고려할 때 베타-글루코시다아제(β-glucosidase)는 클로스트리디움 스테르코라리움(Clostridium stercorarium)에서 유래하는 것이 바람직하고, 클로스트리디움 스테르코라리움 아종 스테르코라리움(Clostridium stercorarium subsp. stercorarium) DSM 8532 균주로부터 유래하는 것이 더 바람직하다. 상기 클로스트리디움 스테르코라리움 아종 스테르코라리움(Clostridium stercorarium subsp. stercorarium) DSM 8532 균주로부터 유래하는 베타-글루코시다아제(β-glucosidase)는 서열번호 1의 아미노산 서열로 구성된다.In addition, considering the reaction efficiency and the physiological activity and diversity of the rare ginsenosides in the conversion of ginsenoside present in ginseng fruit to rare ginsenosides, the beta-glucosidase is a beta-glucosidase, -Glucosidase is preferably derived from Clostridium stercorarium and is preferably derived from Clostridium stercorarium subsp. Stercorarium DSM 8532 strain Is more preferable. The β-glucosidase derived from the Clostridium stercorarium subsp. Stercorarium strain DSM 8532 is composed of the amino acid sequence of SEQ ID NO: 1.
또한, 상기 헤미셀룰라아제(hemicellulase)는 식물 세포벽 구성성분인 자일란, β-1,3-1,4-글루칸, 자일로글루칸, 글루코만난 등을 분해하는 효소에서 선택되며, 바람직하게는 자일라나아제(xylanase), 갈락타나아제(galactanase), 만나나아제(mannanase) 또는 아라비나아제(arabinase)로부터 선택되는 1종 이상으로 구성되고, 인삼열매에 존재하는 진세노사이드에 대한 기질 이용성과 희귀 진세노사이드의 전환 효율 그리고 베타-글루코시다아제(β-glucosidase)와의 조합에 의한 상승 작용 등을 고려할 때 자일라나아제(xylanase)와 갈락타나아제(galactanase)의 조합인 것이 바람직하다.In addition, the hemicellulase is selected from enzymes that decompose plant cell wall components xylan, β-1,3-1,4-glucan, xyloglucan, glucomannan and the like, preferably xylanase ), Galactanase, mannanase, or arabinase, and is characterized in that the substrate availability to the ginsenosides present in the ginseng fruit and that of the rare ginsenosides A combination of xylanase and galactanase is preferable in view of the conversion efficiency and the synergistic action by combination with beta-glucosidase.
또한, 상기 베타-글루코시다아제(β-glucosidase)와 헤미셀룰라아제(hemicellulase)의 혼합 효소에서 베타-글루코시다아제(β-glucosidase) 대 헤미셀룰라아제(hemicellulase)의 혼합 중량비는 크게 제한되지 않으며, 예를 들어 0.1:99.9 내지 99.9:0.1에서 선택될 수 있다. 다만, 효소 처리에 의한 희귀 진세노사이드의 함량 증가 수준을 고려할 때 상기 베타-글루코시다아제(β-glucosidase) 대 헤미셀룰라아제(hemicellulase)의 혼합 중량비는 1:4 내지 4:1인 것이 바람직하다.In addition, the mixing weight ratio of beta-glucosidase to hemicellulase in the mixed enzyme of beta-glucosidase and hemicellulase is not limited to a great extent, May be selected from 0.1: 99.9 to 99.9: 0.1. However, it is preferable that the mixing weight ratio of β-glucosidase to hemicellulase is 1: 4 to 4: 1 in consideration of the increased level of rare ginsenoside by enzyme treatment.
또한, 상기 인삼열매 유래 기질은 효소와의 반응에 의해 Rg1, Rg2, Rg3, Rh1, Rh2, F2, Compound Mc, Compound K 또는 Compound Y에서 선택되는 1종 이상의 희귀 진세노사이드가 반응 전에 비해 증가하고, 바람직하게는 Rg3, Rh1, Rh2, F2, Compound Mc, Compound K 또는 Compound Y에서 선택되는 1종 이상의 희귀 진세노사이드가 반응 전에 비해 증가하는 것을 특징으로 한다.In addition, the ginseng fruit-derived substrate has at least one rare ginsenoside selected from Rg1, Rg2, Rg3, Rh1, Rh2, F2, Compound Mc, Compound K or Compound Y, , Preferably at least one rare ginsenoside selected from Rg3, Rh1, Rh2, F2, Compound Mc, Compound K or Compound Y is increased compared to before the reaction.
목이버섯 균사체Throat mushroom mycelium
목이버섯((Auricularia auricula - judae)은 담자균류 목이과의 버섯으로서 자실체의 지름은 3~12㎝이며 종 모양 또는 귀 모양으로 아교질이고 맥상의 주름이 있다. 목이버섯의 균사체(Mycelia)는 포자가 발아하면서 생성된 균사가 서로 얽힌 집합체로서, 포자를 소정의 배지에서 배양하여 제조할 수 있다. 목이버섯 균사체는 주요 생리활성 성분으로 베타-글루칸(β-Glucan) 등을 포함한다.Thirsty mushroom (( Auricularia auricula - judae ) is a fungus belonging to the fungus family. It has a diameter of 3 ~ 12㎝ and has a bell - shaped or ear - like shape. Mycelia of mycelia of the thymus can be produced by culturing the spores in a predetermined medium, which is an aggregate of mycelia formed by germination of spores. The thymus mushroom mycelium is a major physiologically active ingredient and includes beta-glucan and the like.
인삼열매 유래 기질과 목이버섯 균사체의 혼합 배양Mixed culture of ginseng fruit-derived substrate and thrips mushroom mycelium
본 발명의 다른 예에서 콜레스테롤 저하용 조성물의 유효성분인 인삼열매-목이버섯 균사체 혼합 배양물은 인삼열매 유래 기질을 목이버섯 균사체와 혼합하고 배양하여 얻은 산물이다. 이때, 상기 인삼열매 유래 기질과 목이버섯 균사체의 혼합 중량비는 크게 제한되지 않으며 바람직하게는 1:9 내지 5:5에서 선택되고 2:8 내지 4:6에서 선택된다. 또한, 인삼열매 유래 기질과 목이버섯 균사체의 혼합 배양 온도는 20~30℃에서 선택되고, 배양 시간은 48~72 hr에서 선택될 수 있다.In another example of the present invention, a mixed culture of a ginseng fruit-thistle mushroom mycelium, which is an effective ingredient of a composition for lowering cholesterol, is a product obtained by mixing ginseng fruit-derived substrate with thymus mushroom mycelium. At this time, the mixing weight ratio of the ginseng fruit-derived substrate and the thymus mushroom mycelium is not particularly limited, is preferably selected from 1: 9 to 5: 5, and is selected from 2: 8 to 4: 6. Also, the mixed culture temperature of the ginseng fruit-derived substrate and the thymus mushroom mycelium is selected at 20 to 30 ° C, and the incubation time can be selected from 48 to 72 hr.
본 발명의 조성물은 사용 목적 내지 양상에 따라 약학 조성물, 식품 첨가제, 식품 조성물(특히 건강기능식품) 또는 사료 첨가제 등으로 구체화될 수 있다. 또한, 유효성분인 인삼열매-홍국 혼합 배양물 또는 인삼열매-목이버섯 균사체 혼합 배양물 등의 함량도 조성물의 구체적인 형태, 사용 목적 내지 양상에 따라 다양한 범위에서 조정될 수 있다.The composition of the present invention may be formulated into a pharmaceutical composition, a food additive, a food composition (particularly, a health functional food), a feed additive, or the like depending on the intended use or aspect. The content of ginseng fruit-red flounder mixed culture, ginseng fruit-thistle mushroom mycelial mixed culture, etc., which is an effective ingredient, can also be adjusted in various ranges depending on the specific form of the composition, the purpose of use, and the manner.
본 발명에 따른 약학 조성물에서 유효성분의 함량은 크게 제한되지 않으며, 예를 들어 조성물 총 중량을 기준으로 0.01~99 중량%, 바람직하게는 0.5~50 중량%, 더 바람직하게는 1~30 중량%일 수 있다. 또한, 본 발명에 따른 약학 조성물은 유효성분 외에 약학적으로 허용가능한 담체, 부형제 또는 희석제와 같은 첨가제를 더 포함할 수 있다. 본 발명의 약학 조성물에 포함될 수 있는 담체, 부형제 및 희석제로는 락토즈, 덱스트로즈, 수크로스, 솔비톨, 만니톨, 자일리톨, 에리스리톨, 말티톨, 전분, 아카시아 고무, 알지네이트, 젤라틴, 칼슘 포스페이트, 칼슘 실리케이트, 셀룰로즈, 메틸 셀룰로즈, 미정질 셀룰로스, 폴리비닐 피롤리돈, 물, 메틸히드록시벤조에이트, 프로필히드록시벤조에이트, 탈크, 마그네슘 스테아레이트 및 광물유를 들 수 있다. 또한, 본 발명의 약학 조성물은 콜레스테롤 저하 효능을 갖는 공지의 유효성분을 1종 이상 더 함유할 수 있다. 본 발명의 약학 조성물은 통상의 방법에 의해 경구 투여를 위한 제형 또는 비경구 투여를 위한 제형으로 제제화될 수 있고, 제제화할 경우 보통 사용하는 충진제, 증량제, 결합제, 습윤제, 붕해제, 계면활성제 등의 희석제 또는 부형제를 사용하여 조제될 수 있다. 경구 투여를 위한 고형 제제에는 정제, 환제, 산제, 과립제, 캡슐제 등이 포함되며, 이러한 고형 제제는 유효성분에 적어도 하나 이상의 부형제 예를 들면, 전분, 칼슘카보네이트(Calcium carbonate), 수크로스(Sucrose), 락토오스(Lactose) 또는 젤라틴 등을 섞어 조제될 수 있다. 또한, 단순한 부형제 이외에 마그네슘 스티레이트 탈크 같은 윤활제들도 사용될 수 있다. 경구 투여를 위한 액상 제제로는 현탁제, 내용액제, 유제 및 시럽제 등이 해당되는데 흔히 사용되는 단순희석제인 물, 리퀴드 파라핀 이외에 여러 가지 부형제, 예를 들면 습윤제, 감미제, 방향제, 보존제 등이 포함될 수 있다. 비경구 투여를 위한 제제에는 멸균된 수용액, 비수성용제, 현탁제, 유제, 동결건조제제, 좌제가 포함될 수 있다. 비수성용제, 현탁용제로는 프로필렌글리콜(Propylene glycol), 폴리에틸렌 글리콜, 올리브 오일과 같은 식물성 기름, 에틸올레이트와 같은 주사 가능한 에스테르 등이 사용될 수 있다. 좌제의 기제로는 위텝솔(witepsol), 마크로골, 트윈(tween) 61, 카카오지, 라우린지, 글리세로제라틴 등이 사용될 수 있다. 더 나아가 당 분야의 적정한 방법으로 또는 Remington's Pharmaceutical Science(최근판), Mack Publishing Company, Easton PA에 개시되어 있는 방법을 이용하여 각 질환에 따라 또는 성분에 따라 바람직하게 제제화할 수 있다. 본 발명의 약학 조성물은 목적하는 방법에 따라 인간을 포함한 포유류에 경구 투여되거나 비경구 투여될 수 있으며, 비경구 투여 방식으로는 피부 외용, 복강내주사, 직장내주사, 피하주사, 정맥주사, 근육내 주사 또는 흉부내 주사 주입방식 등이 있다. 본 발명의 약학 조성물의 투여량은 약학적으로 유효한 양이라면 크게 제한되지 않으며, 환자의 체중, 연령, 성별, 건강상태, 식이, 투여시간, 투여방법, 배설율 및 질환의 중증도에 따라 그 범위가 다양하다. 본 발명의 약학 조성물의 통상적인 1일 투여량은 크게 제한되지 않으나 바람직하게는 유효성분을 기준으로 할 때 0.1 내지 3000 ㎎/㎏이고, 더 바람직하게는 1 내지 2000 ㎎/㎏이며, 하루 1회 또는 수회로 나누어 투여될 수 있다.The content of the active ingredient in the pharmaceutical composition according to the present invention is not particularly limited and is, for example, 0.01 to 99% by weight, preferably 0.5 to 50% by weight, more preferably 1 to 30% by weight, Lt; / RTI > In addition, the pharmaceutical composition according to the present invention may further contain, in addition to the active ingredient, an additive such as a pharmaceutically acceptable carrier, excipient or diluent. Examples of carriers, excipients and diluents that can be included in the pharmaceutical composition of the present invention include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate , Cellulose, methylcellulose, microcrystalline cellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil. In addition, the pharmaceutical composition of the present invention may further contain one or more known active ingredients having cholesterol-lowering activity. The pharmaceutical composition of the present invention can be formulated into a formulation for oral administration or parenteral administration by a conventional method, and can be formulated into a pharmaceutical composition such as a filler, an extender, a binder, a wetting agent, a disintegrant, Diluents or excipients. Solid formulations for oral administration include tablets, pills, powders, granules, capsules and the like, which may contain at least one excipient such as starch, calcium carbonate, sucrose ), Lactose, gelatin and the like. In addition to simple excipients, lubricants such as magnesium stearate talc may also be used. Liquid preparations for oral administration include suspensions, solutions, emulsions and syrups. Various excipients such as wetting agents, sweeteners, fragrances, preservatives and the like may be included in addition to water and liquid paraffin, which are simple diluents commonly used. have. Formulations for parenteral administration may include sterile aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations, and suppositories. Propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate, and the like can be used as the non-aqueous solvent and suspension agent. Examples of the suppository base include witepsol, macrogol, tween 61, cacao butter, laurin, glycerogelatin and the like. Further, it can be suitably formulated according to each disease or ingredient, using appropriate methods in the art or by the method disclosed in Remington's Pharmaceutical Science (recent edition), Mack Publishing Company, Easton PA. The pharmaceutical composition of the present invention may be administered orally or parenterally to a mammal including a human according to a desired method. Examples of the parenteral administration method include external dermal application, intraperitoneal injection, intramuscular injection, subcutaneous injection, intravenous injection, Intravenous injection or intra-thoracic injection. The dosage of the pharmaceutical composition of the present invention is not limited as long as it is a pharmacologically effective amount and is not limited as long as it depends on the body weight, age, sex, health condition, diet, administration time, administration method, excretion rate, Varies. The typical daily dose of the pharmaceutical composition of the present invention is not particularly limited, but is preferably 0.1 to 3000 mg / kg, more preferably 1 to 2000 mg / kg, based on the active ingredient, once a day Or may be administered in divided doses.
또한, 본 발명에 따른 식품 조성물에서 유효성분의 함량은 조성물 총 중량을 기준으로 0.01~99 중량%, 바람직하게는 0.1~50 중량%, 더 바람직하게는 0.5~25 중량%이나, 이에 한정되는 것은 아니다. 본 발명의 식품 조성물은 환제, 분말, 과립, 침제, 정제, 캡슐, 또는 액제 등의 형태를 포함하며, 구체적인 식품의 예로는 육류, 소시지, 빵, 초콜릿, 캔디류, 스넥류, 과자류, 피자, 라면, 기타 면류, 껌류, 아이스크림류를 포함한 낙농제품, 각종 스프, 음료수, 차, 기능수, 드링크제, 알코올음료 및 비타민 복합제 등이 있으며, 통상적인 의미에서의 건강기능식품을 모두 포함한다. 본 발명의 식품 조성물은 유효성분 외에 식품학적으로 허용 가능한 담체, 여러 가지 향미제 또는 천연 탄수화물 등을 추가 성분으로서 함유할 수 있다. 또한, 본 발명의 식품 조성물은 여러 가지 영양제, 비타민, 전해질, 풍미제, 착색제, 펙트산 및 그의 염, 알긴산 및 그의 염, 유기산, 보호성 콜로이드 증점제, pH 조절제, 안정화제, 방부제, 글리세린, 알코올, 탄산음료에 사용되는 탄산화제 등을 함유할 수 있다. 그 밖에 본 발명의 식품 조성물은 천연 과일주스, 과일주스 음료 및 야채 음료의 제조를 위한 과육을 함유할 수 있다. 이러한 성분들은 독립적으로 또는 혼합하여 사용할 수 있다. 상술한 천연 탄수화물은 포도당, 과당과 같은 모노사카라이드, 말토스, 수크로스와 같은 디사카라이드, 및 덱스트린, 사이클로덱스트린과 같은 폴리사카라이드, 자일리톨, 소르비톨, 에리트리톨 등의 당알코올이다. 향미제로는 타우마틴, 스테비아 추출물과 같은 천연 향미제나 사카린, 아스파르탐과 같은 합성 향미제 등을 사용할 수 있다.The content of the active ingredient in the food composition according to the present invention is 0.01 to 99% by weight, preferably 0.1 to 50% by weight, more preferably 0.5 to 25% by weight based on the total weight of the composition, no. The food composition of the present invention may be in the form of a pill, a powder, a granule, an infusion, a tablet, a capsule, or a liquid preparation. Examples of the food include meat, sausage, bread, chocolate, candy, snack, Other noodles, gums, dairy products including ice cream, various soups, drinks, tea, functional water, drinks, alcoholic beverages and vitamin complexes. In addition to the active ingredient, the food composition of the present invention may contain a pharmaceutically acceptable carrier, various flavors or natural carbohydrates as an additional ingredient. In addition, the food composition of the present invention can be used as a food composition containing various nutrients, vitamins, electrolytes, flavors, colorants, pectic acids and salts thereof, alginic acid and its salts, organic acids, protective colloid thickeners, pH adjusters, stabilizers, preservatives, , A carbonating agent used in carbonated drinks, and the like. In addition, the food composition of the present invention may contain flesh for the production of natural fruit juices, fruit juice drinks and vegetable drinks. These components may be used independently or in combination. The above-mentioned natural carbohydrates are sugar alcohols such as monosaccharides such as glucose and fructose, disaccharides such as maltose and sucrose, polysaccharides such as dextrin and cyclodextrin, and xylitol, sorbitol and erythritol. Natural flavors such as tau Martin and stevia extract, and synthetic flavors such as saccharin and aspartame may be used as the flavor.
이하, 본 발명을 실시예를 통하여 보다 구체적으로 설명한다. 다만, 하기 실시예는 본 발명의 기술적 특징을 명확하게 예시하기 위한 것일 뿐 본 발명의 보호범위를 한정하는 것은 아니다.Hereinafter, the present invention will be described in more detail with reference to examples. However, the following examples are intended to clearly illustrate the technical features of the present invention and do not limit the scope of protection of the present invention.
1. 인삼열매 착즙액의 제조 및 진세노사이드 조성 분석1. Preparation of juice of ginseng fruit and analysis of ginsenoside composition
포천지역 농가로부터 7월 말에 채취한 미성숙 인삼열매 1종과 8월 말에 채취한 성숙 인삼열매 1종을 각각 40㎏씩 공급받아, 종자를 제거하지 않은 상태로 압착하여 인삼열매 착즙액을 제조하였다. 상기 미성숙 인삼열매는 표피가 주로 초록색을 띠어 GBG(ginseng berry green)로 명명하고 성숙 인삼열매는 표피가 완연한 적색을 나타내어 GBR(ginseng berry red)로 명명한다. 이후, 인삼 착즙액을 15배 정도 농축하여 고형분 농도가 약 60 브릭스(brix)인 인삼열매 착즙 농축액을 제조하였다.One of the immature ginseng fruits collected at the end of July and one of the mature ginseng fruits collected at the end of August from the farms in Pocheon area were supplied with 40 kg of each, and the seeds were squeezed without removing the seeds to produce ginseng fruit juice Respectively. The above-mentioned immature ginseng fruit is named GBG (ginseng berry green) with the epidermis being mainly green, and ginseng berry red is named GBR (ginseng berry red) because the mature ginseng fruit has a reddish color. Then, the ginseng juice was concentrated about 15 times to prepare a concentrate of ginseng fruit juice having a solid concentration of about 60 brix.
인삼열매 착즙 농축액 10g씩을 메탄올에 5배수로 희석하고, 0.2 ㎛ membrane filter로 여과하여 얻은 여과액을 고성능액체크로마토그래피(HPLC) 분석용 시료로 사용하였다. 하기에 HPLC 분석 조건을 나타내었다.10 g of juice concentrate of ginseng fruit juice was diluted with
* 전체 시스템 : Agilent 1200 HPLC 시스템* Complete system: Agilent 1200 HPLC system
* 검출기 및 분석 파장 : UV detector, 203㎚* Detector and analysis wavelength: UV detector, 203 nm
* 이동상 용매 : Acetonitrile (용매 A)와 물 (용매 B)* Mobile phase solvent: Acetonitrile (solvent A) and water (solvent B)
* 이동상 용매의 농도 구배 : 용매 A의 비율을 초기 25%로 시작하고 총 45분에 걸쳐 100%가 될 때가지 점진적으로 증가시킴* Concentration gradient of mobile phase solvent: The ratio of solvent A starts at the initial 25% and progressively increases until it reaches 100% over a total of 45 minutes.
* 표준품 : Facechem사와 Sigma사에서 구매하여 사용* Standard: purchased from Facechem and Sigma
하기 표 1은 GBG 착즙 농축액과 GBR 착즙 농축액의 진세노사이드 조성을 HPLC로 분석한 결과이다. GBG 착즙 농축액과 GBR 착즙 농축액의 총 진세노사이드 함량은 각각 중량 g 당 135.34㎎ 및 174.32㎎ 이었다. GBG 착즙 농축액에서는 진세노사이드 Rd 함량이 가장 높았고, GBR 착즙 농축액에서는 진세노사이드 Re 함량이 가장 높게 나타났다. 이후 실험에서는 효소 반응의 기질로 GBR 착즙 농축액을 사용하였다.Table 1 below shows the results of HPLC analysis of the ginsenoside composition of GBG juice concentrate and GBR juice concentrate. The total ginsenoside content of the GBG juice concentrate and the GBR juice concentrate was 135.34 mg and 174.32 mg per g, respectively. The content of ginsenoside Rd was the highest in GBG juice concentrate and the content of ginsenoside Re was the highest in GBR juice concentrate. In the subsequent experiments, a GBR juice concentrate was used as a substrate for the enzyme reaction.
2. 재조합 베타-글루코시다아제(β-2. Recombinant beta-glucosidase (&bgr; glucosidaseglucosidase )의 )of 클로닝Cloning 및 생산 And production
(1) Dictyoglomus turgidum DSM 6724 균주 유래 재조합 베타-글루코시다아제의 클로닝 및 생산(1) Dictyoglomus Cloning and production of recombinant beta-glucosidase derived from turgidum DSM 6724 strain
Dictyoglomus turgidum DSM 6724 균주 유래 재조합 베타-글루코시다아제(GenBank 번호 : ACK415480; 'DT-BGL'로 명명함) DNA를 공지된 Lee 등((Biotechnol. Lett. 2012, 34(9): 1679)의 방법으로 클로닝하고 형질전환 균주에서 발현시켰다. 이후, 형질전환 균주를 시트레이트-인산 완충액에 희석하고 초음파를 이용하여 파쇄한 후, 원심분리하여 DT-BGL 발현 상등액을 수거하였다. 상기 상등액을 펩티드 태그로 정제하여 정제 DT-BGL을 얻었다. 후술하는 실험에서 DT-BGL 발현 상등액 및 정제 DT-BGL을 선택적으로 사용하였다. DT-BGL은 최적 반응 조건에서 기질인 진세노사이드 Rb1로부터 Rd, F2, Compound K를 거쳐 APPD를 생산하고, 기질인 진세노사이드 Rb2로부터 Compound Y를 생산하며 기질인 진세노사이드 Rc로부터 Compound Mc를 생산한다. DT-BGL의 최적 반응조건은 시트레이트-인산 완충액 50mM, pH 5.5, 반응온도 80℃이다. Dictyoglomus DNA of the turgidum DSM 6724 strain-derived recombinant beta-glucosidase (GenBank number: ACK415480; dubbed DT-BGL) was prepared by the method of Lee et al. (Biotechnol. Lett. 2012, 34 (9): 1679) Then, the transformant strain was diluted with citrate-phosphate buffer, disrupted using ultrasonic waves, and centrifuged to collect DT-BGL expression supernatant. The supernatant was purified with a peptide tag The DT-BGL expression supernatant and the purified DT-BGL were selectively used in the experiments described below. DT-BGL was synthesized from the ginsenoside Rb1 as the substrate, Rd, F2, and Compound K, And the compound Mc from the substrate Ginsenoside Rc The optimal reaction conditions for DT-BGL were: citrate-
(2) 클로스트리디움 스테르코라리움 아종 스테르코라리움(Clostridium stercorarium subsp. stercorarium) DSM 8532 균주 유래 재조합 베타-글루코시다아제의 클로닝 및 생산(2) Cloning and production of recombinant beta-glucosidase derived from Clostridium stercorarium subsp. Stercorarium DSM 8532 strain
클로스트리디움 스테르코라리움 아종 스테르코라리움(Clostridium stercorarium subsp. stercorarium) DSM 8532 균주 유래 재조합 베타-글루코시다아제(GenBank 번호 : AGC67337; 'CS-BGL'로 명명함)는 서열번호 1의 아미노산 서열로 구성되며 Dictyoglomus turgidum DSM 6724 균주 유래 재조합 베타-글루코시다아제 DT-BGL과 아미노산 서열 상동성 차이가 67%이다. 서열번호 2의 염기서열로 구성된 CS-BGL DNA 단편를 중합효소연쇄반응(PCR)으로 증폭하여 확보하였다. 중합효소연쇄반응(PCR)에 사용된 프라이머는 아래와 같으며, 클로닝을 위해 제한효소 NheI과 XhoI을 사용하였다. Clostridium stercorarium subsp. Stercorarium DSM 8532 strain recombinant beta-glucosidase (GenBank number: AGC67337; designated 'CS-BGL') is an amino acid of SEQ ID NO: 1 Dictyoglomus The amino acid sequence homology difference with turgidum DSM 6724 strain-derived recombinant beta-glucosidase DT-BGL is 67%. A CS-BGL DNA fragment consisting of the nucleotide sequence of SEQ ID NO: 2 was amplified by polymerase chain reaction (PCR). The primers used for the PCR were as follows. For the cloning, restriction enzymes NheI and XhoI were used.
Forward primer : 5' -CGGCGCTAGCGTAATACCAATTGTTGCAAGAGTGTC - 3'Forward primer: 5 '-CGGCGCTAGCGTAATACCAATTGTTGCAAGAGTGTC-3'
Reverse primer : 5' - AGTACTCGAGAGCCTGTTCAGCTTTTCCTCGTTCAGTTCC - 3‘Reverse primer: 5 '- AGTACTCGAGAGCCTGTTCAGCTTTTCCTCGTTCAGTTCC -3'
중합효소연쇄반응(PCR)에 사용된 주형 DNA는 다음과 같은 방법으로 확보하였다. 클로스트리디움 스테르코라리움 아종 스테르코라리움(Clostridium stercorarium subsp. stercorarium) DSM 8532 균주를 한천 농도가 15g/ℓ인 Clostridium medium(DSM medium No. 255)에서 접종하고 혐기 조건에서 2일 동안 배양하여 집락을 형성시켰다. 이후, Clostridium medium(DSM medium No. 255) 5㎖가 수용된 vial(Wheaton, 10㎖ 용량)에 질소를 치환하여 산소를 제거한 후 클로스트리디움 스테르코라리움 아종 스테르코라리움(Clostridium stercorarium subsp. stercorarium) DSM 8532 균주의 집락을 접종하고 밀봉한 후 60℃의 온도 및 150 rpm의 교반 조건하에서 30시간 동안 배양하였다. 배양액을 원심분리하여 세포를 회수하고, genomic DNA isolation kit(Bioneer)를 사용하여 회수된 세포로부터 주형 DNA를 확보하였다.The template DNA used in the PCR was obtained by the following method. Clostridium stercorarium subsp. Stercorarium strain DSM 8532 was inoculated in Clostridium medium (DSM medium No. 255) at an agar concentration of 15 g / l and cultured for 2 days in anaerobic condition Colonies were formed. After removing oxygen by replacing nitrogen with vial (Wheaton, 10 ml capacity) containing 5 ml of Clostridium medium (DSM medium No. 255), Clostridium stercorarium ( Clostridium stercorarium) subsp. stercorarium DSM 8532 colonies were inoculated and sealed, and then cultured for 30 hours at a temperature of 60 ° C and a stirring condition of 150 rpm. Cells were recovered by centrifuging the culture, and template DNA was obtained from the recovered cells using a genomic DNA isolation kit (Bioneer).
중합효소연쇄반응(PCR)은 Phusion® High-Fidelity DNA Polymerase kit(NEB)를 사용하여 수행하였고 98℃에서 2분 동안 predenaturation을 실시한 후, denaturation 98℃, 10초; annealing 55℃, 30초; extention 72℃, 130초를 1 cycle로 하여 총 30 cycle을 수행하고 최종적으로 72℃에서 10분 동안 반응시켰다. 이후, agarose gel 전기영동상에서 증폭된 DNA 단편을 확인하고, DNA 단편을 elution 한 후 gel elution kit(Qiagen)를 이용하여 분리하였다. 분리한 DNA 단편을 NheI과 XhoI 제한 효소로 절단한 후 동일한 제한 효소로 처리한 pET-24a 벡터(Novagen)에 cloning 하고 염기서열을 확인하였다. CS-BGL가 클로닝된 pET-24a vector를 pCSBG 플라스미드로 명명하고 상기 플라스미드 50ng을 electroporation을 통해 대장균 ER2566 균주에 형질전환 후 LB-kanamycin 한천 배지에서 단일 집락을 획득하였다. 이후, 획득한 단일 집락을 kanamycin의 농도가 50㎍/㎖인 LB broth에 접종하고 하룻밤 동안 배양하고 이를 종균으로 사용하였다. 상기 종균을 kanamycin의 농도가 50㎍/㎖인 LB broth 500㎖에 접종하고, 37℃의 shaking incubator에서 230 rpm으로 교반배양하면서 배양액의 흡광도(Optical density at 600㎚)가 0.5에 도달하였을 때 IPTG를 최종 농도가 1mM이 되도록 첨가하여 목적 효소의 발현을 유도하고 16℃의 온도 및 150 rpm의 교반 조건에서 15시간 동안 추가로 배양하였다. 배양이 완료된 후, 형질전환 균주의 배양액을 3000rpm에서 20분 동안 원심분리하여 세포를 회수하고, 회수한 세포를 생리식염수로 20회 세척한 후 시트레이트-인산 완충액에 희석하였다. 이후, sonicator(Branson, model 100)를 이용하여 희석된 세포를 파쇄하고, 세포 파쇄액을 14,000 rpm으로 20분 동안 원심분리하여 비가용성 단백질 부분을 제거하고 CS-BGL 발현 상등액을 수거하였다. 또한, 상기 상등액을 pET-24a 벡터에 포함된 히스티딘 태그로 정제하여 정제 CS-BGL을 얻었다. 정제 시 metal ion affinity chromatography(IMAC) cartridge (Bio-Rad)와 immidazole을 사용하였고, 정제 CS-BGL은 시트레이트-인산 완충액에 가용화시킨 후 후술하는 실험에 사용하였다.Polymerase chain reaction (PCR) was performed using the Phusion® High-Fidelity DNA Polymerase kit (NEB), predenaturation at 98 ° C for 2 minutes, denaturation at 98 ° C for 10 seconds; annealing 55 캜, 30 sec; Extension A total of 30 cycles were performed at 72 ° C for 130 seconds as one cycle, and the reaction was finally performed at 72 ° C for 10 minutes. After amplification of the DNA fragments on the agarose gel electrophoresis, the DNA fragments were eluted and then separated by gel elution kit (Qiagen). The isolated DNA fragment was digested with NheI and XhoI restriction enzymes and cloned into pET-24a vector (Novagen) treated with the same restriction enzymes and the nucleotide sequence was confirmed. The pET-24a vector in which CS-BGL was cloned was designated as pCSBG plasmid, and 50 ng of the plasmid was transformed into E. coli ER2566 strain by electroporation and single colonies were obtained in LB-kanamycin agar medium. Then, the obtained single colonies were inoculated into LB broth having a kanamycin concentration of 50 μg / ml and cultured overnight, and used as seeds. The seeds were inoculated into 500 ml of LB broth at a concentration of 50 μg / ml of kanamycin and stirred at 230 rpm in a shaking incubator at 37 ° C. When the optical density at 600 nm reached 0.5, IPTG The final concentration was 1 mM to induce the expression of the target enzyme and further cultured for 15 hours at a temperature of 16 DEG C and a stirring condition of 150 rpm. After the cultivation was completed, the culture medium of the transformant was centrifuged at 3000 rpm for 20 minutes to recover the cells. The recovered cells were washed with
3. 재조합 베타-글루코시다아제에 의한 희귀 진세노사이드의 함량 증대3. Increased content of rare ginsenosides by recombinant beta-glucosidases
시트레이트-인산 완충액(50mM, pH 5.5)에 앞에서 수득한 GBR 착즙 농축액 1g을 넣고 여기에 효소 발현 상등액 2㎖(총 단백질 양은 4㎎임)를 넣은 후 65℃에서 1시간 동안 반응시켰다. 반응 생성물의 진세노사이드 조성을 HPLC로 분석하였고, 그 결과를 하기 표 2에 나타내었다.1 g of the GBR juice concentrate obtained above was added to citrate-phosphate buffer (50 mM, pH 5.5), and 2 ml of the enzyme-expressed supernatant (total amount of protein: 4 mg) was added thereto and reacted at 65 ° C for 1 hour. The ginsenoside composition of the reaction product was analyzed by HPLC and the results are shown in Table 2 below.
Gin Senocide classification
상기 표 2에서 보이는 바와 같이 베타-글루코시다아제 CS-BGL은 진세노사이드 Rh1, Compound MC, Compound Y, Compound K의 생성량 측면에서 베타-글루코시다아제 DT-BGL과 유사하였다. 그러나, 베타-글루코시다아제 CS-BGL은 베타-글루코시다아제 DT-BGL에 비해 진세노사이드 Rg3 및 Rh2를 새롭게 생성시켰고, 진세노사이드 Rg1 및 F2의 생성량도 매우 높았다. 또한, 베타-글루코시다아제 CS-BGL에 의해 기질인 진세노사이드 Rb1은 모두 분해되었고, 진세노사이드 Rd의 함량은 오히려 증가한 것에 비추어볼 때 베타-글루코시다아제 CS-BGL의 반응속도는 PPD(protopanaxadiol) 계열의 진세노사이드에 대해 높은 것으로 보인다. 또한, 베타-글루코시다아제 CS-BGL과의 반응에 의해 진세노사이드 Re의 반응 생성물인 Rg1의 함량이 증가한 것으로 보아, 베타-글루코시다아제 CS-BGL은 PPT(protopanaxatriol) 계열의 진세노사이드 20번 탄소 위치에 존재하는 글루코스를 분해하는 것으로 추정된다.As shown in Table 2, beta-glucosidase CS-BGL was similar to beta-glucosidase DT-BGL in terms of the amount of ginsenoside Rh1, Compound MC, Compound Y and Compound K produced. However, beta-glucosidase CS-BGL newly produced ginsenosides Rg3 and Rh2 as compared to beta-glucosidase DT-BGL, and the amount of ginsenosides Rg1 and F2 was also very high. In addition, since the content of ginsenoside Rb1, which is a substrate, was completely degraded by beta-glucosidase CS-BGL, the content of ginsenoside Rd was rather increased, and the reaction rate of beta-glucosidase CS- protopanaxadiol) family of ginsenosides. In addition, the content of Rg1, which is a reaction product of ginsenoside Re, was increased by the reaction with beta-glucosidase CS-BGL. As a result, beta-glucosidase CS-BGL was found to contain protopanaxatriol (PPT) It is presumed that the glucose present at the carbon position is decomposed.
이를 보다 명확히 확인하기 위해 효소 발현 상등액 대신 정제 DT-BGL 및 정제 CS-BGL을 사용하여 효소 발현 상등액과 동일한 조건으로 반응시켰고 반응 생성물의 미량 진세노사이드인 Rg1, Rg2, Rg3, Rh1, Rh2 및 F2의 함량을 비교하였다. 도 1은 성숙 인삼열매 착즙 농축액을 정제 DT-BGL 및 정제 CS-BGL과 반응시켰을 때 반응 생성물내 진세노사이드의 함량 변화를 나타낸 것이다. 도 1에서 보이는 바와 같이 성숙 인삼열매 착즙 농축액은 정제 CS-BGL과 반응하였을 때 진세노사이드 Rg3 및 Rh1의 함량이 각각 반응전보다 8배 및 2배 이상 증가하였다. 또한, 정제 CS-BGL은 정제 DT-BGL에 비해 진세노사이드 Rh2 및 F2를 새롭게 생성시켰고, 다른 미량 진세노사이드 생성량도 더 높은 것으로 나타났다. 결과적으로 베타-글루코시다아제 CS-BGL은 인삼열매 착즙 농축액 내 진세노사이드와 반응하여 미량 진세노사이드의 함량을 골고루 증가시킬 수 있는 것으로 판단된다.Rg1, Rg2, Rg3, Rh1, Rh2 and F2 of the reaction product were reacted under the same conditions as the enzyme expression supernatant using purified DT-BGL and purified CS-BGL in place of the enzyme expression supernatant. Were compared. Figure 1 shows the content of ginsenosides in the reaction product when the juice concentrate of matured ginseng fruit was reacted with purified DT-BGL and purified CS-BGL. As shown in FIG. 1, the content of ginsenosides Rg3 and Rh1 in the juice concentrate of mature ginseng juice was 8 times and 2 times higher than that in the case of the reaction with purified CS-BGL, respectively. In addition, purified CS-BGL produced more ginsenosides Rh2 and F2 than purified DT-BGL, and the other trace ginsenosides produced were also higher. As a result, it is considered that beta-glucosidase CS-BGL can react with ginsenoside in the concentrate of ginseng fruit juice concentrate to increase the content of trace ginsenoside evenly.
4. 4. 헤미셀룰라아제에Hemicellulase 의한 희귀 진세노사이드의 함량 증대 Increased content of rare ginsenosides by
시트레이트-인산 완충액(50mM, pH 5.5)에 앞에서 수득한 GBR 착즙 농축액 1g을 넣고 여기에 상업적 효소인 헤미셀룰라아제 2㎖를 넣은 후 35℃에서 1시간 동안 반응시켰다. 반응 생성물의 진세노사이드 조성을 HPLC로 분석하였고, 그 결과를 하기 표 3에 나타내었다. 상기 상업적 효소인 헤미셀룰라아제는 자일라나아제(xylanase)와 갈락타나아제(galactanase)로 구성되어 있고, 일본 기업인 Amno사의 제품이다.1 g of the GBR juice concentrate obtained above was added to citrate-phosphate buffer (50 mM, pH 5.5), 2 ml of hemicellulase as a commercial enzyme was added thereto, and the mixture was reacted at 35 ° C for 1 hour. The ginsenoside composition of the reaction product was analyzed by HPLC and the results are shown in Table 3 below. The hemicellulase, which is a commercial enzyme, is composed of xylanase and galactanase, and is a product of Japanese company Amno.
상기 표 3에서 보이는 바와 같이 헤미셀룰라아제는 아라비노스 또는 자일로스가 함유된 진세노사이드 Rb2, Rb3, Rc 또는 R2를 분해하여 진세노사이드 Rd, Rh1 또는 Compound Mc 등의 함량을 증가시키는데에 효과가 있었다. 또한, 헤미셀룰라아제는 진세노사이드 R2를 모두 분해시켜 진세노사이드 Rh1으로 전환시켰고, 그 결과 Rh1이 반응 후 약 3.2배 증가하였다. 또한, GBR 착즙 농축액과 헤미셀룰라아제의 반응 후 진세노사이드 Re의 반응 산물인 진세노사이드 Rg1 및 Rg2의 함량이 각각 1.3배씩 증가하였다. 또한, GBR 착즙 농축액과 헤미셀룰라아제의 반응 후 진세노사이드 Rc는 Compound Mc로 30% 이상 전환되었다. 또한, 헤미셀룰라아제는 GBR 착즙 농축액 내 진세노사이드 Rb2 및 Rb3를 각각 23% 및 50.8% 정도 분해하였고, 진세노사이드 Rb1을 약 30% 이상 분해하여 모두 Rd로 전환시켰다. 결론적으로, 헤미셀룰라아제는 종래 효소 처리로 분해가 어려운 진세노사이드의 아라비노스나 자일로스를 효과적으로 분해하여 인삼열매 착즙 농축액 내 다양한 미량 진세노사이드 함량을 유의적으로 증가시킬 수 있다.As shown in Table 3, hemicellulase was effective in decomposing ginsenosides Rb2, Rb3, Rc, or R2 containing arabinose or xylose to increase contents of ginsenoside Rd, Rh1 or Compound Mc . In addition, the hemicellulase completely decomposed ginsenoside R2 and converted it into ginsenoside Rh1. As a result, Rh1 increased about 3.2 times after the reaction. In addition, the content of ginsenosides Rg1 and Rg2, which are reaction products of ginsenoside Re, increased by 1.3 times after the reaction of GBR juice concentrate and hemicellulase. In addition, after the reaction of GBR juice concentrate with hemicellulase, ginsenoside Rc was converted to Compound Mc by more than 30%. Hemicellulase also decomposed ginsenosides Rb2 and Rb3 in GBR juice concentrate by 23% and 50.8%, respectively, and decomposed more than 30% of ginsenoside Rb1 into all Rd. In conclusion, hemicellulase effectively decomposes arabinose and xylose of ginsenoside, which is difficult to degrade by conventional enzyme treatment, and can significantly increase various trace ginsenoside contents in ginseng fruit juice concentrate.
5. 베타-글루코시다아제와 5. Beta-glucosidase and 헤미셀룰라아제의Hemicellulase 혼합 효소에 의한 희귀 진세노사이드의 함량 증대 Increased content of rare ginsenosides by mixed enzymes
시트레이트-인산 완충액(50mM, pH 5.5)에 앞에서 수득한 GBR 착즙 농축액 1g을 넣고 여기에 베타-글루코시다아제와 헤미셀룰라아제의 혼합 효소 2㎖를 넣은 후 65℃에서 1시간 동안 반응시켰다. 반응 생성물의 진세노사이드 조성을 HPLC로 분석하였고, 그 결과를 하기 표 4에 나타내었다. 상기 베타-글루코시다아제는 CS-BGL 발현 상등액이다. 또한, 상기 상업적 효소인 헤미셀룰라아제는 자일라나아제(xylanase)와 갈락타나아제(galactanase)로 구성되어 있고, 일본 기업인 Amno사의 제품이다. 하기 표 4에서 보이는 바와 같이 베타-글루코시다아제와 헤미셀룰라아제의 혼합 효소는 GBR 착즙 농축액 내 미량 진세노사이드 함량을 현저하게 증가시켰다. 이는 혼합 효소가 PPD 계열의 진세노사이드와 PPT 계열의 진세노사이드를 모두 기질로 사용하고 골고루 분해한 것에서 기인하는 것으로 판단된다.1 g of the GBR juice concentrate obtained above was added to citrate-phosphate buffer (50 mM, pH 5.5), and 2 ml of a mixed enzyme of beta-glucosidase and hemicellulase was added thereto, followed by reaction at 65 ° C for 1 hour. The ginsenoside composition of the reaction product was analyzed by HPLC and the results are shown in Table 4 below. The beta-glucosidase is a CS-BGL expression supernatant. The hemicellulase, which is a commercial enzyme, is composed of xylanase and galactanase, and is a product of Amno, a Japanese company. As shown in Table 4 below, the mixed enzyme of beta-glucosidase and hemicellulase significantly increased the content of trace ginsenosides in the GBR juice concentrate. It is considered that the mixed enzyme was caused by the decomposition of both the PPD series of ginsenosides and the PPT series of ginsenosides both as substrates and evenly.
* 혼합 효소 1 : 베타-글루코시다아제와 헤미셀룰라아제의 혼합 중량비가 1:4임Mixed enzyme 1: Mixed weight ratio of beta-glucosidase to hemicellulase is 1: 4
* 혼합 효소 2 : 베타-글루코시다아제와 헤미셀룰라아제의 혼합 중량비가 1:1임Mixed Enzyme 2: Mixture weight ratio of 1: 1 beta-glucosidase to hemicellulase
* 혼합 효소 3 : 베타-글루코시다아제와 헤미셀룰라아제의 혼합 중량비가 4:1임Mixed enzyme 3: Mixture weight ratio of beta-glucosidase to hemicellulase is 4: 1
6. 6. 증숙Steam 가공(Steaming Steaming proceeprocee )에 의한 희귀 진세노사이드의 함량 증대) To increase the content of rare ginsenosides
(1) 사포닌 수율을 기준으로 한 최적 증숙 가공 조건 확립(1) Establishment of optimal steaming process conditions based on saponin yield
미성숙 인삼열매 또는 성숙 인삼열매를 소정의 압력 및 소정의 온도 조건에서 스팀으로 15시간 증숙 가공한 후 압착하여 인삼열매 착즙액을 제조하였다. 이후, 인삼열매 착즙액을 농축하고 고성능액체크로마토그래피(HPLC)를 이용하여 사포닌 함량을 분석하였다.The immature ginseng fruit or the mature ginseng fruit was steamed for 15 hours under a predetermined pressure and a predetermined temperature condition, and pressed to produce a ginseng fruit juice. Then, the sap of the ginseng fruit juice was concentrated and analyzed for its saponin content by high performance liquid chromatography (HPLC).
도 2는 성숙 인삼열매를 상압(게이지 압력으로 환산하면 0 atm에 해당함; 절대압력 = 대기압(1 atm) + 게이지 압력) 및 다양한 온도 조건에서 스팀으로 15시간 증숙 가공하였을 때 인삼열매 착즙액의 사포닌 수율 변화를 나타낸 것이다. 도 2에서 사포닌 수율은 증숙 가공 온도 조건이 60℃였을 때를 100%로 하여 상대적으로 나타낸 것이다. 도 2에서 보이는 바와 같이 증숙 가공 온도 조건이 50~70℃였을 때 인삼열매 착즙액의 사포닌 수율이 가장 높게 나타났다.FIG. 2 is a graph showing the effect of the saponin content of ginseng fruit juice on the matured ginseng fruit when steamed for 15 hours under various pressures (atmospheric pressure (1 atm) + gauge pressure) at normal pressure (equivalent to 0 atm in terms of gauge pressure) Yield change. In FIG. 2, the saponin yield is shown as 100% when the steaming temperature is 60 ° C. As shown in FIG. 2, the saponin yield of the juice of ginseng fruit juice was highest when the boiling temperature was 50 to 70 ° C.
도 3은 성숙 인삼열매를 다양한 압력 조건 및 60℃의 온도 조건에서 스팀으로 15시간 증숙 가공하였을 때 인삼열매 착즙액의 사포닌 수율 변화를 나타낸 것이다. 도 3에서 X축의 기압은 게이지 압력을 나타낸다. 또한, 도 3에서 사포닌 수율은 증숙 가공 압력 조건이 상압(게이지 압력으로 환산하면 0 atm에 해당함; 절대압력 = 대기압(1 atm) + 게이지 압력)이였을 때를 100%로 하여 상대적으로 나타낸 것이다. 도 3에서 보이는 바와 같이 증숙 가공 압력 조건이 게이지 압력을 기준으로 0.4~1 atm일 때 인삼열매 착즙액의 사포닌 수율이 가장 높게 나타났다.FIG. 3 shows changes in saponin yield of ginseng fruit juice when matured ginseng was steamed for 15 hours under various pressure conditions and temperature conditions of 60 ° C. In Fig. 3, the air pressure on the X axis represents the gauge pressure. In FIG. 3, the saponin yield is expressed as 100% when the boiling pressure condition is atmospheric pressure (equivalent to 0 atm in terms of gauge pressure, absolute pressure = atmospheric pressure (1 atm) + gauge pressure). As shown in FIG. 3, the saponin yield of the ginseng fruit juice was highest when the boiling pressure was 0.4 to 1 atm based on the gauge pressure.
도 2 내지 도 3으로부터 사포닌 수율을 기준으로 한 인삼열매의 최적 증숙 가공 조건은 50~70℃의 온도, 0.4~1 atm의 게이지 압력 및 2~24 hr의 처리 시간인 것으로 확인되었다. 본 발명의 인삼열매 증숙 가공은 상대적으로 저온에서 실시되므로 기존의 고온 증숙 가공에 비해 벤조피렌과 같은 유해성분은 감소하고 희귀 진세노사이드의 함량은 증가한다.From FIGS. 2 to 3, it was confirmed that the optimal processing conditions of the ginseng fruit on the basis of the saponin yield were a temperature of 50 to 70 DEG C, a gauge pressure of 0.4 to 1 atm and a treatment time of 2 to 24 hr. Since the processing of ginseng berries according to the present invention is carried out at a relatively low temperature, harmful components such as benzopyran are reduced and the content of rare ginsenosides is increased compared to the conventional high-temperature steaming process.
(2) 최적 증숙 가공 조건으로 전처리된 인삼열매 착즙액의 진세노사이드 조성 분석(2) Ginsenoside composition analysis of ginseng fruit juice pretreated with optimal steaming conditions
미성숙 인삼열매 또는 성숙 인삼열매를 1 atm의 게이지 압력 및 60℃의 온도 조건에서 스팀으로 15시간 증숙 가공한 후 압착하여 인삼열매 착즙액을 제조하였다. 이후, 인삼열매 착즙액을 농축하고 고성능액체크로마토그래피(HPLC)를 이용하여 사포닌 함량을 분석하였고 그 결과를 하기 표 5에 나타내었다.Immature ginseng fruit or mature ginseng fruit was steamed for 15 hours at a gauge pressure of 1 atm and temperature of 60 ℃, and pressed to produce ginseng fruit juice. Then, the sap of the ginseng fruit was concentrated and analyzed for its saponin content by high performance liquid chromatography (HPLC). The results are shown in Table 5 below.
상기 표 5에서 보이는 바와 같이 증숙 가공된 인삼열매는 증숙 가공 전에 비해 Rg1, Rg2, Rg3, Rh1, Rh2, F1, F2와 같은 희귀 진세노사이드 함량이 크게 증가하였다.As shown in Table 5, the ginsenoside contents such as Rg1, Rg2, Rg3, Rh1, Rh2, F1 and F2 of the ginseng fruit were significantly increased compared to those before the boiling.
7. 인삼열매-7. Ginseng fruit - 홍국Hongkuk 혼합 배양물, 인삼열매-목이버섯 균사체 혼합 배양물 등의 제조 및 활성 성분 분석 Mixed culture, preparation of mixed culture of ginseng fruit-throat mushroom mycelium and analysis of active ingredient
(1) 홍국의 제조(1) Production of red yeast
한국종균협회(Korean Federation of Culture Collections, KFCC)의 부설 균주기탁 및 보존기관인 한국미생물보존센터(Korean Culture Center of Microorganisms, KCCM)로부터 Monascus pilosus IFO 4480(기탁번호 KCCM 60396 균주와 동일한 균주임)을 분양받았다. 홍국균 균주인 Monascus pilosus IFO 4480(기탁번호 KCCM 60396 균주와 동일한 균주임)를 PDA 배지(potato dextrose agar medium; Difco, MI, USA)에서 30℃의 온도로 8일 동안 배양하고 포자 및 균사체를 액체 배지에 현탁하여 홍국균 포자 현탁액을 제조하였다. 이후, 121℃에서 30분 동안 고압증기멸균 처리하여 증자한 백미를 자연 방냉 후 홍국균 포자 현탁액을 건조 균체량으로 환산하여 0.2g/㎏의 양으로 접종하고 30℃의 온도 및 80%의 습도 조건에서 18일 동안 배양하여 홍국을 제조하였다. 홍국 제조 과정에서 홍국균 배양체 덩어리를 1일에 2번씩 흔들어 주어 덩어리 형성을 방지하였다.From the Korean Culture Center of Microorganisms (KCCM), a deposit and conservation organization of the Korean Federation of Culture Collections (KFCC), Monascus pilosus IFO 4480 (same strain as KCCM 60396 strain). Monascus pilosus IFO 4480 (the same strain as KCCM 60396 strain) was cultured in a potato dextrose agar medium (Difco, MI, USA) at a temperature of 30 ° C for 8 days, and the spore and mycelium were suspended in a liquid medium, Spore suspension. Thereafter, the white rice grown by high pressure steam sterilization treatment at 121 ° C for 30 minutes was spontaneously cooled, and the sprout suspension of Hongwook gonococci was inoculated in an amount of 0.2 g / kg in terms of dry cell weight. For 12 days. During the production of Hongkuk, the Hongkuk culture broth was shaken twice a day to prevent lump formation.
(2) 인삼열매-홍국 혼합 배양물의 제조(2) Preparation of ginseng fruit-red yeast mixed culture
상기에서 제조한 홍국 700g 및 최적 증숙 가공 조건(1 atm의 게이지 압력 및 60℃의 온도에서 15시간 처리)으로 전처리된 성숙 인삼열매 착즙 농축액 300g을 균일하게 혼합하고 30℃의 온도 및 70%의 습도 조건에서 약 30시간 동안 배양하여 인삼열매-홍국 혼합 배양물을 제조하였다.300 g of the red ginseng fruit juice concentrate prepared as above and 300 g of the mature ginseng fruit juice concentrate pretreated with optimal steaming conditions (treated at a gauge pressure of 1 atm and a temperature of 60 ° C for 15 hours) were uniformly mixed and heated at a temperature of 30 ° C. and a humidity of 70% For 30 hours to prepare a ginseng fruit - red yeast mixed culture.
(3) 목이버섯 균사체의 제조(3) Preparation of mycelia of throat mushroom
목이버섯의 포자 배양액을 PDA 배지(potato dextrose agar medium; Difco, MI, USA)에 접종하고 4℃에서 보존하면서 3개월 마다 계대배양 하였다. 목이버섯 포자가 충분히 배양된 한천 배지로부터 목이버섯 포자가 형성된 부분을 1㎝×1㎝의 크기로 약 10개 정도 절단하여 분리하고 액체 배지(pH 5.0)에 넣고 회전식 진탕 배양기에서 25℃의 온도 및 130 rpm의 조건으로 약 7일 동안 종균 배양하였다. 이후, 종균 배양액을 미리 제조한 액체 배지(글루코스 20g/L, MgSO4·7H2O 0.5 g/L, KH2PO4 0.46 g/L, K2HPO4 1 g/L, 효모추출물 2 g/L, 펩톤 2 g/L; 멸균하기 전 pH는 5.0임)에 5%(v/v)의 양으로 접종하고 회전식 진탕 배양기에서 25℃의 온도 및 120 rpm의 조건으로 약 10일 동안 배양하여 목이버섯 균사체를 제조하였다.The spore culture of the thymus mushroom was inoculated into PDA medium (Difco, MI, USA) and stored at 4 ° C and subcultured every 3 months. From the agar medium which had been sufficiently cultivated, about 10 pieces of the spore mushroom spores were cut and separated into liquid medium (pH 5.0), and the mixture was incubated at 25 ° C And seed culture was carried out for about 7 days under the condition of 130 rpm. Thereafter, the culture medium of the seed culture was cultured in a liquid medium (glucose 20 g / L, MgSO 4 .7H 2 O 0.5 g / L, KH 2 PO 4 0.46 g / L, K 2 HPO 4 1 g / L, yeast extract 2 g / L) and peptone (2 g / L; pH before sterilization was 5.0) in an amount of 5% (v / v) and incubated for about 10 days at 25 ° C. and 120 rpm in a rotary shaking incubator Mushroom mycelia were prepared.
(4) 인삼열매-목이버섯 균사체 혼합 배양물의 제조(4) Preparation of mixed culture of ginseng fruit-thymus mushroom mycelium
상기에서 제조한 목이버섯 균사체 700g 및 최적 증숙 가공 조건(1 atm의 게이지 압력 및 60℃의 온도에서 15시간 처리)으로 전처리된 성숙 인삼열매 착즙 농축액 300g을 균일하게 혼합하고 25℃의 온도 및 120 rpm의 조건으로 약 60시간 동안 배양하여 인삼열매-목이버섯 균사체 혼합 배양물을 제조하였다.700 g of the mushroom mycelia prepared above and 300 g of the mature ginseng fruit juice concentrate which had been pretreated with the optimal steaming processing conditions (treatment at 1 atm gauge pressure and temperature of 60 ° C. for 15 hours) were uniformly mixed and heated at 25 ° C. and 120 rpm For about 60 hours to prepare a mixed culture of ginseng fruit-thistle mushroom mycelium.
(5) 모나콜린 K의 함량 분석(5) Analysis of content of monocholin K
시료 0.2g에 추출 용매로 100% methanol 1㎖를 넣고 25℃에서 20분간 sonication 한 후 8,000×g에서 10분간 원심분리하여 상등액을 수득하였다. 또한, 원심분리에 의해 얻은 침전물에 1㎖의 추출 용매를 첨가하여 위와 동일한 방법으로 모나콜린-K를 추출하였으며 5회 반복하여 최종 추출물 5㎖를 수득하였다. 이후, 추출물을 syringe filter로 여과하고 여과된 추출물 10㎕를 HPLC 장치에 주입하여 아래와 같은 조건으로 분석하였다.To 0.2 g of the sample was added 1 ml of 100% methanol as an extraction solvent, sonicated at 25 ° C for 20 minutes, and then centrifuged at 8,000 × g for 10 minutes to obtain a supernatant. In addition, 1 mL of the extraction solvent was added to the precipitate obtained by centrifugation, monacolin-K was extracted in the same manner as above, and repeated 5 times to obtain 5 mL of the final extract. Then, the extract was filtered with a syringe filter, and 10 μl of the filtered extract was injected into an HPLC apparatus and analyzed under the following conditions.
* 분석 칼럼 : Merck LiChrospher 100 RP-18* Analysis Column:
* 전개 용매 : acetonitrile : 0.1% trifluoacetic acid (60:40)* Developing solvent: acetonitrile: 0.1% trifluoacetic acid (60:40)
* 전개 유속 : 1㎖/min* Developed flow rate: 1 ml / min
이후, 분석 결과를 표준 모나콜린-K(Sigma-aldrich Co., USA)와 비교하여 각각의 시료에 함유되어 있는 비활성형 모나콜린-K(Lactone form)의 양을 측정하였다.Thereafter, the results were compared with a standard monocholine-K (Sigma-aldrich Co., USA) to determine the amount of the inactive monacolin-K (Lactone form) contained in each sample.
(6) 베타-글루칸 함량 분석(6) Analysis of beta-glucan content
액체 배양 시료를 10,447×g에서 20분간 원심분리하여 얻은 침전물을 수득하고 건조하여 농축하였다. 이후, 침전물 100 g에 추출 용매로 2,000 ㎖의 증류수를 넣고 100℃의 중탕으로 24시간 동안 추출한 후 원심분리하여 상등액을 수득하였다. 또한, 원심분리 후 남은 잔사에 추출 용매로 다시 2,000 ㎖의 증류수를 넣고 100℃의 중탕으로 24시간 동안 추출하였고, 총 3회 반복추출하여 추출액을 수득하였다. 이후, 추출액을 감압 농축하여 농축액 100 ㎖를 수득하였다. 이후, 농축액의 온도를 4℃로 유지시키고 여기에 -20℃로 빙냉시킨 300 ㎖ 에탄올을 넣고 4시간 동안 4℃에서 방치하였다. 이후, 농축액으로부터 침전물을 분리하고 Beta-glucan assay kit(Megazyme.co)를 이용하여 베타-글루칸(β-Glucan)의 함량을 측정하였다.The liquid culture sample was centrifuged at 10,447 x g for 20 minutes to obtain a precipitate, which was dried and concentrated. Then, 2,000 ml of distilled water was added as an extraction solvent to 100 g of the precipitate, and the mixture was extracted with a hot bath at 100 ° C for 24 hours, followed by centrifugation to obtain a supernatant. Further, 2,000 ml of distilled water was further added as an extraction solvent to the remaining residue after centrifugation, and the mixture was extracted with a hot bath at 100 ° C for 24 hours, and extracted three times to obtain an extract. Thereafter, the extract was concentrated under reduced pressure to obtain 100 ml of a concentrated solution. Thereafter, the temperature of the concentrate was maintained at 4 캜, 300 ml ethanol ice-cooled at -20 캜 was added thereto, and the mixture was allowed to stand at 4 캜 for 4 hours. Then, the precipitate was separated from the concentrate and the content of β-glucan was measured using a Beta-glucan assay kit (Megazyme. Co.).
(7) 혼합 배양물의 활성 성분 분석 결과(7) Analysis of active components of mixed cultures
하기 표 6에 홍국, 인삼열매-홍국 혼합 배양물, 목이버섯 균사체, 인삼열매-목이버섯 균사체 혼합 배양물에 함유된 활성 성분 분석 결과를 나타내었다.Table 6 shows the results of the analysis of the active ingredients contained in the mixed cultures of red ginseng, ginseng fruit-red ginseng mixed culture, throat mushroom mycelium, and ginseng fruit-thistle mushroom mycelium.
(㎎/㎏)Mona Colin K
(Mg / kg)
(㎎/㎏)Total saponin
(Mg / kg)
(㎎/L)Beta-glucan
(Mg / L)
상기 표 6에서 보이는 바와 같이 인삼열매-홍국 혼합 배양물 또는 인삼열매-목이버섯 균사체 혼합 배양물에서 모나콜린 K, 사포닌, 베타-글루칸과 같은 다양한 활성 성분이 생성되었다.As shown in Table 6, various active ingredients such as monacolin K, saponin, and beta-glucan were produced in a mixed culture of ginseng fruit-red flounder mixed culture or ginseng fruit-thistle mushroom mycelium.
8. 8. 홍국Hongkuk , 인삼열매-, Ginseng fruit - 홍국Hongkuk 혼합 배양물, 목이버섯 균사체, 인삼열매-목이버섯 균사체 혼합 배양물, 인삼열매- Mixed culture, mycelium of mushroom, mixed culture of ginseng fruit - thistle mushroom mycelium, ginseng fruit - 홍국Hongkuk -목이버섯 균사체 혼합 배양물의 혈중 콜레스테롤 저하 효능 확인을 위한 in-vivo 실험- In-vivo experiment for checking cholesterol lowering effect of mixed culture of mycelia
SD rat를 구입하여 1주일간 기본 식이 만을 공급하여 사육실 환경에 적응시켰다. 기본 식이는 5L79 Rat/Mouse Formula 18%(PMI Nutrition LLC, Po Box 19798 Brentwood Mo63144, USA)로 crude porotein(minimum) 18%, crude fat(minimum 5%, fiber(maximum) 5%, ash(maximum) 8%, carbohydrate 64%인 것을 사용하였다. 사육실 온도는 22±2℃, 습도는 60±5%로 조정하였고, 명암 주기(light-dark cycle)는 12시간 단위로 조절하였다.SD rats were purchased and adapted to the feeding environment by feeding only basic diets for 1 week. The crude diet contained crude porothe- tan (minimum) 18%, crude fat (minimum 5%,
이후, 1주일간 환경에 적응시킨 실험동물을 무작위로 선택하여 한 군당 6마리씩 총 8개의 군으로 나누고 정상 식이군을 제외한 나머지 실험군의 실험동물에 1% cholesterol과 0.25% sodium cholate를 함유한 고 콜레스테롤 식이를 4주간 급여하여 고지혈증을 유발시켰다. 정상 식이군의 실험 동물에는 기본 식이를 급여하였다. 이후 각 실험군의 실험동물에게 1주일간 약물 시료를 1% Tween-80에 녹인 다음 10 ㎎/㎏ b.w의 용량으로 경구 투여하였다. 각 실험군에 투여한 약물 시료는 다음과 같다.Thereafter, animals were randomly selected to be environmentally adapted for 1 week, divided into 8 groups of 6 animals per group. In the experimental animals except for the normal diet group, high cholesterol diet containing 1% cholesterol and 0.25% sodium cholate For 4 weeks to induce hyperlipemia. The animals in the normal diet group were fed a basic diet. Then, drug samples were dissolved in 1% Tween-80 for 1 week and then administered orally at a dose of 10 ㎎ / ㎏ bw. Drug samples administered to each experimental group were as follows.
* 정상 식이군 : 약물 시료를 투여하지 않고 기본 식이만을 급여함* Normal diet group: Only basic diet is fed without drug sample
* 양성 대조군 : 고 콜레스테롤 식이를 섭취시킨 후 약물 시료로 콜레스테롤 저하 약물인 프로부콜(probucol)을 투여함* Positive Control: After taking a high cholesterol diet, the patient is given cholesterol lowering drug, probucol.
* A군 : 고 콜레스테롤 식이를 섭취시킨 후 약물 시료로 홍국을 투여함* Group A: Red ginseng is administered as a drug sample after high cholesterol diet
* B군 : 고 콜레스테롤 식이를 섭취시킨 후 약물 시료로 인삼열매-홍국 혼합 배양물을 투여함* Group B: After taking high cholesterol diet, ginseng fruit-red mixed culture was administered as a drug sample.
* C군 : 고 콜레스테롤 식이를 섭취시킨 후 약물 시료로 목이버섯 균사체를 투여함* Group C: After taking a high cholesterol diet, mycelium of throat mushroom was administered as a drug sample.
* D군 : 고 콜레스테롤 식이를 섭취시킨 후 약물 시료로 인삼열매-목이버섯 균사체 혼합 배양물을 투여함* Group D: After taking high cholesterol diet, mixed culture of ginseng fruit-throat and mushroom mycelium was administered as a drug sample.
* E군 : 고 콜레스테롤 식이를 섭취시킨 후 약물 시료로 인삼열매-홍국-목이버섯 균사체 혼합 배양물을 투여함* Group E: After ingesting high cholesterol diet, mixed culture of ginseng fruit - red ginseng - thymus mushroom mycelium was administered as a drug sample
* 인삼열매-홍국-목이버섯 균사체 혼합 배양물 : 인삼열매-홍국 혼합 배양물 및 인삼열매-목이버섯 균사체 혼합 배양물을 동량으로 혼합하여 제조함* Mixed culture of ginseng fruit - red ginseng - thymus mushroom mycelium: mixed ginseng fruit - red ginseng mixed culture and ginseng fruit - thistle mushroom mycelium mixed culture
투여실험이 끝난 후 rat을 CO2로 가볍게 마취시키고 복부대동맥으로부터 혈액을 채취하고 실온에서 30분간 방치한 후 3,000 rpm에서 10분간 원심분리하여 혈청을 분리하였다. 이후, 혈청 중 HDL-C(high density lipoprotein cholesterol)의 함량을 Noma 등의 효소법에 의하여 조제된 kit(sigma, USA)를 사용하여 측정하였고 LDL-C(low density lipoprotein cholesterol)의 함량을 Fridewald 등의 방법에 따라 산출하였다. 하기 표 7에 약물 시료가 실험동물의 혈중 콜레스테롤 함량에 미치는 결과를 나타내었다.After the administration, the rats were lightly anesthetized with CO 2 , the blood was collected from the abdominal aorta, left at room temperature for 30 minutes, and centrifuged at 3,000 rpm for 10 minutes to separate the serum. The content of high density lipoprotein cholesterol (HDL-C) in serum was measured using a kit (Sigma, USA) prepared by the enzyme method such as Noma and the content of LDL-C (low density lipoprotein cholesterol) Method. Table 7 shows the results of the drug samples on the blood cholesterol content of the experimental animals.
상기 표 7에서 보이는 바와 같이 인삼열매-홍국 혼합 배양물 및 인삼열매-목이버섯 균사체 혼합 배양물은 각각 홍국 및 목이버섯 균사체에 비해 실험동물의 콜레스테롤을 더 감소시켰고 인삼열매-홍국-목이버섯 균사체 혼합 배양물의 경우 실험동물의 콜레스테롤을 현저하게 감소시켰다.As shown in Table 7, the mixed cultures of the ginseng fruit-red flounder mixed cultures and the ginseng fruit-thistle mushroom mycelial cultures further reduced the cholesterol of the experimental animals compared with the mycelia of the red and thrips mushrooms, respectively, and the ginseng fruit-red ginseng- In the case of the culture, the cholesterol of the experimental animals was remarkably reduced.
9. 인삼열매-9. Ginseng fruit - 홍국Hongkuk 혼합 배양물, 인삼열매-목이버섯 균사체 혼합 배양물의 Mixed culture, ginseng fruit-throat mushroom mycelial mixed culture 헤미셀룰라아제Hemicellulase 처리에 의한 희귀 진세노사이드의 함량 변화 Changes in the content of rare ginsenosides by treatment
시트레이트-인산 완충액(50mM, pH 5.5)에 앞에서 제조한 인삼열매-홍국 혼합 배양물 또는 인삼열매-목이버섯 균사체 혼합 배양물 1g을 넣고 여기에 상업적 효소인 헤미셀룰라아제 2㎖를 넣은 후 35℃에서 1시간 동안 반응시켰다. 반응 생성물의 진세노사이드 조성을 HPLC로 분석하였고, 그 결과를 하기 표 8 및 표 9에 나타내었다. 상기 상업적 효소인 헤미셀룰라아제는 자일라나아제(xylanase)와 갈락타나아제(galactanase)로 구성되어 있고, 일본 기업인 Amno사의 제품이다.To the citrate-phosphate buffer solution (50 mM, pH 5.5), 1 g of the mixed culture of the ginseng fruit-red ginseng mixture or the ginseng fruit-thistle mushroom mycelium prepared above was added and 2 ml of hemicellulase, a commercial enzyme, was added thereto. And reacted for 1 hour. The ginsenoside composition of the reaction product was analyzed by HPLC and the results are shown in Tables 8 and 9 below. The hemicellulase, which is a commercial enzyme, is composed of xylanase and galactanase, and is a product of Japanese company Amno.
이상에서와 같이 본 발명을 상기의 실시예를 통해 설명하였지만 본 발명이 반드시 여기에만 한정되는 것은 아니며 본 발명의 범주와 사상을 벗어나지 않는 범위 내에서 다양한 변형실시가 가능함은 물론이다. 따라서, 본 발명의 보호범위는 특정 실시 형태로 국한되는 것이 아니며, 본 발명에 첨부된 특허청구의 범위에 속하는 모든 실시 형태를 포함하는 것으로 해석되어야 한다.While the present invention has been particularly shown and described with reference to exemplary embodiments thereof, it is to be understood that the invention is not limited to the disclosed exemplary embodiments, but, on the contrary, is intended to cover various modifications and equivalent arrangements included within the spirit and scope of the appended claims. Accordingly, the scope of protection of the present invention is not limited to the specific embodiments but should be construed as including all embodiments belonging to the claims attached hereto.
<110> Global Hub Co., Ltd. <120> Composition for lowering cholesterol comprising a mixture culture of Ginseng Berry-Auricularia auricula mycelia <130> DP-17-467 <160> 2 <170> KoPatentIn 3.0 <210> 1 <211> 794 <212> PRT <213> Unknown <220> <223> beta-glucosidase derived from Clostridium stercorarium subsp. stercorarium DSM 8532 <400> 1 Met Val Ile Pro Ile Val Ala Arg Val Ser Glu Lys Val Ile Ile Tyr 1 5 10 15 Tyr Ala Gly Thr Val Tyr Glu Asn Leu Asn Asp Lys Gly Ile Thr Gly 20 25 30 Val Ile Lys Met Gln Arg Asp Ile Lys Lys Ile Ile Ser Gln Met Thr 35 40 45 Leu Glu Glu Lys Ala Ser Leu Cys Ser Gly Leu Asp Ala Trp Asn Leu 50 55 60 Lys Ser Val Glu Arg Leu Gly Ile Pro Ser Ile Met Val Ser Asp Gly 65 70 75 80 Pro His Gly Leu Arg Lys Glu Thr Thr Asp Pro Thr Asp Pro Gly Lys 85 90 95 Lys Thr Thr Val Pro Ala Thr Cys Phe Pro Thr Ala Val Gly Leu Ala 100 105 110 Ser Ser Trp Asn Arg Glu Leu Val Glu Lys Val Gly Ala Ala Leu Gly 115 120 125 Glu Glu Cys Gln Ala Glu Gly Ile Ala Val Leu Leu Gly Pro Gly Thr 130 135 140 Asn Ile Lys Arg Ser Pro Leu Cys Gly Arg Asn Phe Glu Tyr Phe Ser 145 150 155 160 Glu Asp Pro Tyr Leu Ser Ser Glu Met Ala Ala Ser His Ile Lys Gly 165 170 175 Val Gln Ser Arg Gly Val Gly Thr Ser Leu Lys His Phe Ala Ala Asn 180 185 190 Asn Gln Glu His Arg Arg Met Ser Val Asp Ala Val Ile Asp Glu Arg 195 200 205 Thr Leu Arg Glu Ile Tyr Leu Ala Ser Phe Glu Gly Ala Val Lys Lys 210 215 220 Ala Lys Pro Trp Thr Ile Met Cys Ser Tyr Asn Arg Val Asn Gly Glu 225 230 235 240 Tyr Ala Ser Glu Asn Lys Phe Leu Leu Thr Asp Val Leu Arg Asn Glu 245 250 255 Trp Gly Phe Glu Gly Ile Val Val Ser Asp Trp Gly Ala Val Asn Glu 260 265 270 Arg Val Lys Gly Leu Glu Ala Gly Leu Asp Leu Glu Met Pro Ser Ser 275 280 285 Phe Gly Ile Gly Asp Gln Lys Ile Val Glu Ala Val Lys Lys Gly Glu 290 295 300 Leu Pro Glu Glu Val Leu Asp Arg Thr Val Glu Arg Ile Leu Asn Leu 305 310 315 320 Ile Phe Lys Ala Val Asp Asn Arg Lys Glu Asn Ala Gly Tyr Asp Arg 325 330 335 Glu Ala His His Lys Leu Ala Arg Glu Ala Ala Arg Glu Cys Met Val 340 345 350 Leu Leu Lys Asn Glu Asp Lys Ile Leu Pro Leu Arg Lys Gln Gly Thr 355 360 365 Ile Ala Val Ile Gly Glu Phe Ala Lys Arg Pro Arg Tyr Gln Gly Gly 370 375 380 Gly Ser Ser His Val Asn Pro Thr Ile Met Asp Ser Pro Tyr Glu Glu 385 390 395 400 Ile Lys Lys Ser Ala Gly Asn Asn Ala Asp Val Ile Tyr Ala Gln Gly 405 410 415 Tyr Phe Ile Glu Lys Asp Glu Pro Asp Glu Lys Leu Leu Glu Glu Ala 420 425 430 Lys Gln Ala Ala Leu Lys Ala Asp Val Ala Val Ile Phe Ala Gly Leu 435 440 445 Pro Glu His Tyr Glu Cys Glu Gly Tyr Asp Arg Gln His Met Arg Met 450 455 460 Pro Glu Ser His Cys Thr Leu Ile Glu Glu Val Ala Lys Val Gln Pro 465 470 475 480 Asn Val Val Val Val Leu Cys Asn Gly Ser Pro Val Glu Met Pro Trp 485 490 495 Ile Asp Lys Val Lys Gly Leu Leu Glu Ala Tyr Leu Gly Gly Gln Ala 500 505 510 Met Gly Gly Ala Ile Ala Asp Leu Leu Phe Gly Asp Ala Asn Pro Ser 515 520 525 Gly Lys Leu Ala Glu Thr Phe Pro Lys Gln Leu Ser Asp Asn Pro Ser 530 535 540 Tyr Leu Asn Phe Pro Gly Glu Gly Asp Arg Val Glu Tyr Arg Glu Gly 545 550 555 560 Ile Phe Val Gly Tyr Arg Tyr Tyr Asp Lys Lys Asn Met Glu Pro Leu 565 570 575 Phe Pro Phe Gly Tyr Gly Leu Ser Tyr Thr Thr Phe Glu Tyr Gly Asp 580 585 590 Leu Lys Ile Ser Arg Lys Glu Ile Ser Asp Asn Glu Thr Val Thr Val 595 600 605 Ser Val Lys Val Lys Asn Thr Gly Asp Met Ala Gly Lys Glu Ile Val 610 615 620 Gln Leu Tyr Val Arg Asp Ile Glu Ser Ser Val Ile Arg Pro Glu Lys 625 630 635 640 Glu Leu Lys Gly Phe Glu Lys Val Glu Leu Lys Pro Gly Glu Glu Lys 645 650 655 Thr Val Val Phe Glu Leu Asp Lys Arg Ala Phe Ala Tyr Tyr Asn Thr 660 665 670 Gly Ile Arg Asp Trp His Val Glu Thr Gly Glu Phe Glu Ile Leu Ile 675 680 685 Gly Arg Ser Ser Arg Asp Ile Val Leu Lys Asp Lys Ile Phe Val Lys 690 695 700 Ser Thr Val Thr Ile Lys Lys Pro Val Asp Arg Asn Thr Leu Val Gly 705 710 715 720 Asp Leu Leu Ser Asp Arg Val Leu Glu Pro Val Phe Arg Glu Phe Ile 725 730 735 Ile Asn Glu Ile Lys Asn Arg Tyr Leu Leu Asp Leu Leu Glu Asn Glu 740 745 750 Asp Lys Ser Leu Leu Ser Val Trp Met Arg Tyr Thr Pro Leu Arg Ser 755 760 765 Leu Ala Asn Ser Thr Gly Gly Glu Leu Asn Glu Glu Lys Leu Asn Arg 770 775 780 Leu Ile Asp Thr Leu Asn Ala Asn Ile Lys 785 790 <210> 2 <211> 2385 <212> DNA <213> Unknown <220> <223> DNA fragment encoding beta-glucosidase derived from Clostridium stercorarium subsp. stercorarium DSM 8532 <400> 2 gtggtaatac caattgttgc aagagtgtct gagaaagtta taatttatta tgccggaacg 60 gtttacgaaa atttgaacga taaaggcata acaggagtga taaaaatgca aagggacatc 120 aaaaaaatta tttcacaaat gacgctggaa gaaaaggcga gcttatgctc gggccttgac 180 gcctggaacc ttaaaagcgt agaacgtttg ggcattccgt ccattatggt atctgacggc 240 ccccatggtc tcagaaaaga gacaacggat cccactgatc ccggtaagaa aaccactgtc 300 ccggccacat gtttccccac tgcggttggc cttgcaagct catggaaccg tgaactggtg 360 gagaaagtag gcgccgcatt gggggaagaa tgccaggctg aaggaatagc agtgcttctt 420 gggccgggaa ccaatataaa acgttcccct ctttgcggaa gaaactttga atatttttcg 480 gaagacccgt acctttcttc ggagatggca gcaagccata taaaaggagt gcagagccgg 540 ggagtgggga cgtccctgaa gcattttgcg gcaaataacc aggaacaccg cagaatgagc 600 gtggatgcgg taattgacga aagaacgctg cgtgaaattt acctcgccag tttcgaaggg 660 gcggttaaaa aggcgaagcc gtggacgatc atgtgttcat acaacagggt aaacggcgag 720 tatgcatctg aaaataaatt tctgttaaca gatgtactga gaaatgaatg gggttttgaa 780 ggcattgtgg tatccgactg gggagcggtg aatgagaggg taaagggact ggaagccgga 840 cttgatcttg aaatgccgtc aagcttcggt attggagacc aaaaaatagt tgaagccgta 900 aagaagggtg agctgcccga agaggtattg gacagaaccg ttgaaaggat acttaattta 960 atttttaaag cggtggataa caggaaagaa aatgccggat atgaccggga agctcatcac 1020 aaactggcca gagaagcggc aagggagtgc atggtgctgc ttaagaacga ggacaaaata 1080 cttccgctta ggaagcaggg aaccatagcc gtaataggcg aatttgctaa aagaccacgg 1140 tatcagggcg gaggaagctc ccatgtaaat cccacaatca tggatagtcc atatgaagaa 1200 atcaaaaaat cagcgggaaa caatgcagat gttatatatg cgcaaggtta ttttattgaa 1260 aaggacgagc cagatgaaaa actcctggag gaagcaaagc aggcggcgct gaaggcagat 1320 gtcgccgtga tatttgcagg gcttcccgag cattatgaat gcgagggcta tgaccgtcag 1380 catatgagaa tgcccgaaag ccactgcacg cttatcgaag aagtggcgaa agtacaaccc 1440 aatgtggtgg tggtattatg caacggttca ccggtggaga tgccgtggat tgacaaagtg 1500 aagggattgc tggaggctta cctgggcgga caagccatgg gcggagccat tgccgatctt 1560 ctgttcggag acgccaatcc cagcgggaag ctcgccgaga ctttcccgaa acagttaagc 1620 gataaccctt catatttgaa ttttcccggg gaaggggaca gggttgaata cagggaaggc 1680 atattcgtgg gctacaggta ttatgacaaa aagaatatgg aaccgctgtt cccgttcgga 1740 tacgggctca gctacactac gtttgagtac ggcgatctga aaataagcag gaaagaaata 1800 tctgataacg aaacggtgac tgtgagcgta aaggttaaga ataccggaga tatggcgggt 1860 aaggagattg tgcagcttta cgtaagggat attgaaagct cggtaataag accggagaag 1920 gaactgaagg gttttgaaaa agttgaactt aagcccggcg aggaaaaaac ggtggtgttt 1980 gaacttgaca agagggcgtt tgcttattac aacaccggta taagggactg gcatgttgaa 2040 accggtgaat ttgagatttt aataggcaga tcctcaaggg acatagtgct taaagacaag 2100 atattcgtca aatcaaccgt taccataaaa aaaccggtgg acagaaacac gctggtgggg 2160 gatttgcttt ctgatcgggt tcttgagcct gtattcagag agtttattat taacgagata 2220 aaaaacaggt acttgttgga tttactggag aacgaggata aatccctcct gagtgtgtgg 2280 atgaggtata ctcctctgcg ttcattggcg aacagtacgg gtggggaact gaacgaggaa 2340 aagctgaaca ggctgattga tacactgaat gcaaatatta aataa 2385 <110> Global Hub Co., Ltd. <120> Composition for lowering cholesterol comprising a mixture culture of Ginseng Berry-Auricularia auricula mycelia <130> DP-17-467 <160> 2 <170> KoPatentin 3.0 <210> 1 <211> 794 <212> PRT <213> Unknown <220> <223> beta-glucosidase derived from Clostridium stercorarium subsp. stercorarium DSM 8532 <400> 1 Met Val Ile Pro Ile Val Ala Arg Val Ser Glu Lys Val Ile Ile Tyr 1 5 10 15 Tyr Ala Gly Thr Val Tyr Glu Asn Leu Asn Asp Lys Gly Ile Thr Gly 20 25 30 Val Ile Lys Met Gln Arg Asp Ile Lys Lys Ile Ser Ser Gln Met Thr 35 40 45 Leu Glu Glu Lys Ala Ser Leu Cys Ser Gly Leu Asp Ala Trp Asn Leu 50 55 60 Lys Ser Val Glu Arg Leu Gly Ile Pro Ser Ile Met Val Ser Asp Gly 65 70 75 80 Pro His Gly Leu Arg Lys Glu Thr Thr Asp Pro Thr Asp Pro Gly Lys 85 90 95 Lys Thr Thr Val Ala Thr Cys Phe Pro Thr Ala Val Gly Leu Ala 100 105 110 Ser Ser Trp Asn Arg Glu Leu Val Glu Lys Val Gly Ala Ala Leu Gly 115 120 125 Glu Cys Gln Ala Glu Gly Ile Ala Val Leu Leu Gly Pro Gly Thr 130 135 140 Asn Ile Lys Arg Ser Pro Leu Cys Gly Arg Asn Phe Glu Tyr Phe Ser 145 150 155 160 Glu Asp Pro Tyr Leu Ser Ser Glu Met Ala Ala Ser His Ile Lys Gly 165 170 175 Val Gln Ser Arg Gly Val Gly Thr Ser Leu Lys His Phe Ala Ala Asn 180 185 190 Asn Gln Glu His Arg Arg Met Ser Val Asp Ala Val Ile Asp Glu Arg 195 200 205 Thr Leu Arg Glu Ile Tyr Leu Ala Ser Phe Glu Gly Ala Val Lys Lys 210 215 220 Ala Lys Pro Trp Thr Ile Met Cys Ser Tyr Asn Arg Val Asn Gly Glu 225 230 235 240 Tyr Ala Ser Glu Asn Lys Phe Leu Leu Thr Asp Val Leu Arg Asn Glu 245 250 255 Trp Gly Phe Glu Gly Ile Val Val Ser Asp Trp Gly Ala Val Asn Glu 260 265 270 Arg Val Lys Gly Leu Glu Ala Gly Leu Asp Leu Glu Met Pro Ser Ser 275 280 285 Phe Gly Ile Gly Asp Gln Lys Ile Val Glu Ala Val Lys Lys Gly Glu 290 295 300 Leu Pro Glu Glu Val Leu Asp Arg Thr Val Glu Arg Ile Leu Asn Leu 305 310 315 320 Ile Phe Lys Ala Val Asp Asn Arg Lys Glu Asn Ala Gly Tyr Asp Arg 325 330 335 Glu Ala His His Lys Leu Ala Arg Glu Ala Ala Arg Glu Cys Met Val 340 345 350 Leu Leu Lys Asn Glu Asp Lys Ile Leu Pro Leu Arg Lys Gln Gly Thr 355 360 365 Ile Ala Val Ile Gly Glu Phe Ala Lys Arg Pro Arg Tyr Gln Gly Gly 370 375 380 Gly Ser Ser His Val Asn Pro Thr Ile Met Asp Ser Pro Tyr Glu Glu 385 390 395 400 Ile Lys Lys Ser Ala Gly Asn Asn Ala Asp Val Ile Tyr Ala Gln Gly 405 410 415 Tyr Phe Ile Glu Lys Asp Glu Pro Asp Glu Lys Leu Leu Glu Glu Ala 420 425 430 Lys Gln Ala Ala Leu Lys Ala Asp Val Ala Val Ile Phe Ala Gly Leu 435 440 445 Pro Glu His Tyr Glu Cys Glu Gly Tyr Asp Arg Gln His Met Arg Met 450 455 460 Pro Glu Ser His Cys Thr Leu Ile Glu Glu Val Ala Lys Val Gln Pro 465 470 475 480 Asn Val Val Val Leu Cys Asn Gly Ser Pro Val Glu Met Pro Trp 485 490 495 Ile Asp Lys Val Lys Gly Leu Leu Gly Aly Tyr Leu Gly Gly Gln Ala 500 505 510 Met Gly Gly Ala Ile Ala Asp Leu Leu Phe Gly Asp Ala Asn Pro Ser 515 520 525 Gly Lys Leu Ala Glu Thr Phe Pro Lys Gln Leu Ser Asp Asn Pro Ser 530 535 540 Tyr Leu Asn Phe Pro Gly Glu Gly Asp Arg Val Glu Tyr Arg Glu Gly 545 550 555 560 Ile Phe Val Gly Tyr Arg Tyr Tyr Asp Lys Lys Asn Met Glu Pro Leu 565 570 575 Phe Pro Phe Gly Tyr Gly Leu Ser Tyr Thr Thr Phe Glu Tyr Gly Asp 580 585 590 Leu Lys Ile Ser Arg Lys Glu Ile Ser Asp Asn Glu Thr Val Thr Val 595 600 605 Ser Val Lys Val Lys Asn Thr Gly Asp Met Ala Gly Lys Glu Ile Val 610 615 620 Gln Leu Tyr Val Arg Asp Ile Glu Ser Ser Val Ile Arg Pro Glu Lys 625 630 635 640 Glu Leu Lys Gly Phe Glu Lys Val Glu Leu Lys Pro Gly Glu Glu Lys 645 650 655 Thr Val Phe Glu Leu Asp Lys Arg Ala Phe Ala Tyr Tyr Asn Thr 660 665 670 Gly Ile Arg Asp Trp His Val Glu Thr Gly Glu Phe Glu Ile Leu Ile 675 680 685 Gly Arg Ser Ser Arg Asp Ile Val Leu Lys Asp Lys Ile Phe Val Lys 690 695 700 Ser Thr Val Thr Ile Lys Lys Pro Val Asp Arg Asn Thr Leu Val Gly 705 710 715 720 Asp Leu Leu Ser Asp Arg Val Leu Glu Pro Val Phe Arg Glu Phe Ile 725 730 735 Ile Asn Glu Ile Lys Asn Arg Tyr Leu Leu Asp Leu Leu Glu Asn Glu 740 745 750 Asp Lys Ser Leu Leu Ser Val Trp Met Arg Tyr Thr Pro Leu Arg Ser 755 760 765 Leu Ala Asn Ser Thr Gly Gly Glu Leu Asn Glu Glu Lys Leu Asn Arg 770 775 780 Leu Ile Asp Thr Leu Asn Ala Asn Ile Lys 785 790 <210> 2 <211> 2385 <212> DNA <213> Unknown <220> <223> DNA fragment encoding beta-glucosidase derived from Clostridium stercorarium subsp. stercorarium DSM 8532 <400> 2 gtggtaatac caattgttgc aagagtgtct gagaaagtta taatttatta tgccggaacg 60 gtttacgaaa atttgaacga taaaggcata acaggagtga taaaaatgca aagggacatc 120 aaaaaaatta tttcacaaat gacgctggaa gaaaaggcga gcttatgctc gggccttgac 180 gcctggaacc ttaaaagcgt agaacgtttg ggcattccgt ccattatggt atctgacggc 240 ccccatggtc tcagaaaaga gacaacggat cccactgatc ccggtaagaa aaccactgtc 300 ccggccacat gtttccccac tgcggttggc cttgcaagct catggaaccg tgaactggtg 360 gagaagtag gcgccgcatt gggggaagaa tgccaggctg aaggaatagc agtgcttctt 420 gggccgggaa ccaatataaa acgttcccct ctttgcggaa gaaactttga atatttttcg 480 gaagacccgt acctttcttc ggagatggca gcaagccata taaaaggagt gcagagccgg 540 ggagtgggga cgtccctgaa gcattttgcg gcaaataacc aggaacaccg cagaatgagc 600 gtggatgcgg taattgacga aagaacgctg cgtgaaattt acctcgccag tttcgaaggg 660 gcggttaaaa aggcgaagcc gtggacgatc atgtgttcat acaacagggt aaacggcgag 720 tatgcatctg aaaataaatt tctgttaaca gatgtactga gaaatgaatg gggttttgaa 780 ggcattgtgg tatccgactg gggagcggtg aatgagaggg taaagggact ggaagccgga 840 cttgatcttg aaatgccgtc aagcttcggt attggagacc aaaaaatagt tgaagccgta 900 aagaagggtg agctgcccga agaggtattg gacagaaccg ttgaaaggat acttaattta 960 atttttaaag cggtggataa caggaaagaa aatgccggat atgaccggga agctcatcac 1020 aaactggcca gagaagcggc aagggagtgc atggtgctgc ttaagaacga ggacaaaata 1080 cttccgctta ggaagcaggg aaccatagcc gtaataggcg aatttgctaa aagaccacgg 1140 tatcagggcg gaggaagctc ccatgtaaat cccacaatca tggatagtcc atatgaagaa 1200 atcaaaaaat cagcgggaaa caatgcagat gttatatatg cgcaaggtta ttttattgaa 1260 aaggacgagc cagatgaaaa actcctggag gaagcaaagc aggcggcgct gaaggcagat 1320 gtcgccgtga tatttgcagg gcttcccgag cattatgaat gcgagggcta tgaccgtcag 1380 catatgagaa tgcccgaaag ccactgcacg cttatcgaag aagtggcgaa agtacaaccc 1440 aatgtggtgg tggtattatg caacggttca ccggtggaga tgccgtggat tgacaaagtg 1500 aagggattgc tggaggctta cctgggcgga caagccatgg gcggagccat tgccgatctt 1560 ctgttcggag acgccaatcc cagcgggaag ctcgccgaga ctttcccgaa acagttaagc 1620 gataaccctt catatttgaa ttttcccggg gaaggggaca gggttgaata cagggaaggc 1680 atattcgtgg gctacaggta ttatgacaaa aagaatatgg aaccgctgtt cccgttcgga 1740 tacgggctc gctacactac gtttgagtac ggcgatctga aaataagcag gaaagaaata 1800 tctgataacg aaacggtgac tgtgagcgta aaggttaaga ataccggaga tatggcgggt 1860 aaggagattg tgcagcttta cgtaagggat attgaaagct cggtaataag accggagaag 1920 gaactgaagg gttttgaaaa agttgaactt aagcccggcg aggaaaaaac ggtggtgttt 1980 gaacttgaca agagggcgtt tgcttattac aacaccggta taagggactg gcatgttgaa 2040 accggtgaat ttgagatttt aataggcaga tcctcaaggg acatagtgct taaagacaag 2100 atattcgtca aatcaaccgt taccataaaa aaaccggtgg acagaaacac gctggtgggg 2160 gatttgcttt ctgatcgggt tcttgagcct gtattcagag agtttattat taacgagata 2220 aaaaacaggt acttgttgga tttactggag aacgaggata aatccctcct gagtgtgtgg 2280 atgaggtata ctcctctgcg ttcattggcg aacagtacgg gtggggaact gaacgaggaa 2340 aagctgaaca ggctgattga tacactgaat gcaaatatta aataa 2385
Claims (9)
상기 인삼열매-목이버섯 균사체 혼합 배양물은 인삼열매 유래 기질을 목이버섯 균사체와 1:9 내지 5:5의 중량비로 혼합하고 배양하여 얻은 산물이고,
상기 인삼열매-홍국 혼합 배양물은 인삼열매 유래 기질을 홍국균 또는 홍국과 혼합하고 배양하여 얻은 산물이고,
상기 인삼열매 유래 기질은 인삼열매 착즙액, 인삼열매 추출액 또는 이들의 농축액에서 선택되거나 인삼열매 착즙액, 인삼열매 추출액 또는 이들의 농축액과 효소와의 반응에 의해 얻은 산물에서 선택되고,
상기 효소는 베타-글루코시다아제(β-glucosidase), 헤미셀룰라아제(hemicellulase) 또는 이들의 혼합 효소에서 선택되는 것을 특징으로 하는 콜레스테롤 저하용 조성물.
A mixed culture of ginseng fruit-throat mushroom mycelium and a mixed culture of ginseng fruit-red ginseng root, or a composition comprising these as an active ingredient,
The mixed culture of the ginseng fruit-thistle mushroom mycelium is a product obtained by mixing the ginseng fruit-derived substrate with the thymus mushroom mycelium at a weight ratio of 1: 9 to 5: 5,
The ginseng fruit-red flounder mixed culture is a product obtained by mixing ginseng fruit-derived substrate with red ginseng or red yeast,
Wherein the substrate derived from ginseng fruit is selected from the extracts of ginseng fruit juice, extracts of ginseng fruit, or concentrates thereof, or products obtained by reaction of ginseng fruit juice extract, ginseng fruit extract or concentrates thereof with an enzyme,
Wherein the enzyme is selected from beta-glucosidase, hemicellulase, or a mixed enzyme thereof.
The composition for lowering cholesterol according to claim 1, wherein the ginseng fruit is mature fruit.
The composition for lowering cholesterol according to claim 1, wherein the beta-glucosidase is derived from Clostridium stercorarium .
4. The composition for lowering cholesterol according to claim 3, wherein the beta-glucosidase is an amino acid sequence of SEQ ID NO: 1.
The hemicellulase according to claim 1, wherein the hemicellulase is at least one selected from the group consisting of xylanase, galactanase, mannanase, and arabinase. Wherein the cholesterol-lowering composition is a composition for reducing cholesterol.
The composition for lowering cholesterol according to claim 1, wherein the weight ratio of the β-glucosidase to the hemicellulase is 1: 4 to 4: 1.
The ginseng fruit-derived substrate according to claim 1, wherein the ginseng fruit-derived substrate comprises at least one rare ginsenoside selected from Rg1, Rg2, Rg3, Rh1, Rh2, F2, Compound Mc, Wherein the cholesterol-lowering agent is added to the composition.
The composition for lowering cholesterol according to claim 1, wherein the ginseng fruit is pretreated by boiling.
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