KR20190055785A - Ginsenoside composition for treating, improving, or preventing inflammatory disease, and method for preparing the same - Google Patents
Ginsenoside composition for treating, improving, or preventing inflammatory disease, and method for preparing the same Download PDFInfo
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- KR20190055785A KR20190055785A KR1020190054841A KR20190054841A KR20190055785A KR 20190055785 A KR20190055785 A KR 20190055785A KR 1020190054841 A KR1020190054841 A KR 1020190054841A KR 20190054841 A KR20190054841 A KR 20190054841A KR 20190055785 A KR20190055785 A KR 20190055785A
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- ginsenoside
- composition
- arthritis
- treatment
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Classifications
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- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
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- A61K36/258—Panax (ginseng)
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- A—HUMAN NECESSITIES
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- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
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- A61K31/7034—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
- A61K31/704—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin
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- A—HUMAN NECESSITIES
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- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2200/00—Function of food ingredients
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
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Abstract
Description
본 발명은 진세노사이드 조성물 및 그의 제조방법에 관한 것으로, 더욱 상세하게는 기존의 인삼 진세노사이드를 대사시켜 생리활성이 이전과는 다른 새로운 조성물들을 얻으며, 이를 통해 염증성 질환에 대한 예방 및 치료에도 효과가 있는 조성물을 얻는 방법에 관한 것이다.The present invention relates to a ginsenoside composition and a method for producing the same, and more particularly, to obtain a new composition having a different physiological activity than before by metabolizing the existing ginseng ginsenoside, through which it is also used in the prevention and treatment of inflammatory diseases. It relates to a method of obtaining a composition that works.
인삼 또는 홍삼의 주요 생리 활성 성분이 포함된 사포닌 성분은 타 식물에서 발견되는 사포닌과 화학 구조가 상이한 바, 이를 특별히 인삼(Ginseng) 배당체 (Glycoside)란 의미로 진세노사이드(ginsenoside)라 명명되고 있다. 이와 같은 진세노사이드는 아글리콘(aglycone)의 구조에 따라 프로토파낙사이다이올계 (Protopanaxadiol-type), 프로토파낙사트라이올계 (Protopanaxatriol-type), 및 올레아놀린산계 (Oleanolic acid-type) 진세노사이드 등 세 가지로 분류될 수 있다. 이러한 세 그룹은 다시, 화합물 구조 중 고리의 C-3, C-6 및 C-20 위치의 글라이코시딕 결합 (glycoside bond)에 의해 부착되는 당 부위 (sugar moieties (aglycones))의 위치 및 수에 따라 분류되는데, 그 중 Rg1, Re, Rb1, Rc 및 Rb2 는 전체 사포닌의 90% 이상을 차지하는 메이저 진세노사이드 (major ginsenoside)이고 (Park, 2004), 이들은 큰 사이즈로 인하여 인체에 경구 투여되는 경우, 직접 흡수되기 어렵다고 알려져 있다. 따라서, 이러한 메이저 진세노사이드들은, 생체 시험(in vivo test)에서 생리적 활성을 효과적으로 나타내기 위하여, 당을 제거 (deglycosylated)하는 전환과정이 요구된다 (Tawab et al., 2003; Akao et al.,1998). 한편, 최근 수십 년간 Rg3, Rh2 및 화합물 K(compound K)등 마이너 형태(minor form)를 갖는 진세노사이드들의 뛰어난 약리효능이 밝혀지고 있다. 이러한 연구결과가 발표됨에 따라 보다 우수한 약리 작용을 갖는 진세노사이드들 F2, Rg3, Rh1, Rh2 및 화합물 K(compound K, C-K), Gyp17, Rg3, C-Mc1, C-Mx1, F2 등 미량의 마이너 진세노사이드들(minor ginsenosides)에 대한 많은 연구가 이루어지고 있으며, 이러한 마이너 형태를 갖는 특정 진세노사이드의 함량 비율을 증가시킬 수 있는 방법이 요구되고 있는 실정이다.The saponin component, which contains the main physiologically active ingredients of ginseng or red ginseng, has a chemical structure different from that of saponins found in other plants, and it is specifically named as ginsenoside in the sense of Ginseng glycoside. . Such ginsenosides are Protopanaxadiol-type, Protopanaxatriol-type, and oleanolic acid-type ginsenosides according to the structure of aglycone. It can be classified into three categories: These three groups are again the position and number of sugar moieties (aglycones) attached by glycoside bonds at the C-3, C-6 and C-20 positions of the ring in the compound structure. Among them, Rg1, Re, Rb1, Rc, and Rb2 are major ginsenosides, which account for more than 90% of the total saponin (Park, 2004), and these are orally administered to the human body due to their large size. In this case, it is known that it is difficult to be absorbed directly. Therefore, these major ginsenosides require a conversion process that removes sugar (deglycosylated) in order to effectively exhibit physiological activity in an in vivo test (Tawab et al., 2003; Akao et al., 1998). On the other hand, in recent decades, excellent pharmacological efficacy of ginsenosides having minor forms such as Rg3, Rh2 and compound K (compound K) has been revealed. As these research results are published, trace amounts of ginsenosides F2, Rg3, Rh1, Rh2 and compounds K (compound K, CK), Gyp17, Rg3, C-Mc1, C-Mx1, F2, etc. There are many studies on minor ginsenosides, and there is a demand for a method capable of increasing the content ratio of a specific ginsenoside having such a minor form.
미량의 사포닌인 마이너 진세노사이드들을 생산하기 위한 방법으로 화학적 분해 방법 (De Mayo 등, canad. J. Chem., 43, 2033, 1965), 효소적 방법 (Kitagawa등, Terahedron Letters, 30, 2283, 1974), 및 배당체 합성을 이용한 방법 (제10-2005-0007250호) 등이 제시되어 왔으나, 상기와 같은 방법들은 1) 제조 공정상 여러 단계를 거쳐야 하거나, 2) 제조과정에서 목적하는 성분이 소실되며, 3) 식용에 부적합한 촉매를 사용하거나, 4) 낮은 수율을 나타내어 여전히 대량생산에 한계가 존재하여 왔다. Chemical decomposition method (De Mayo et al., canad. J. Chem., 43, 2033, 1965), enzymatic method (Kitagawa et al., Terahedron Letters, 30, 2283, as a method for producing minor ginsenosides, which is a trace amount of saponin). 1974), and a method using the synthesis of glycosides (No. 10-2005-0007250), etc., have been proposed, but such methods 1) require several steps in the manufacturing process, or 2) the desired component is lost in the manufacturing process. And, 3) using a catalyst that is not suitable for food, or 4) showing a low yield, there has still been a limit to mass production.
특히 효소적 방법 중, 사용될 수 있는 효소의 종류로 진세노사이드 글라이코시데이즈 (ginsenoside glycosidase), α-L-아라비노피라노시데이즈 (α-arabinopyranosidase), α-L-아라비노퓨라노시데이즈 (α-L-arabinofuranosidase), α-L-람노시데이즈 (α-L-rhamnosidase)와 같은 효소가 Rb1, Rb2, Rc 및 Re와 같은 메이저 진세노사이드들을 생전환(biotransformation)함이 보고되고 있다. 즉, 인삼으로부터 추출한 사포닌들은 대부분 Rg1, Re, Rb1, Rb2, Rc 및 Rb3 등의 복합 사포닌들로 형성되어 있어 글라이코시딕 결합에 의해 결합되어 있는 당들의 부착 수, 종류와 위치 등이 상이하여 여러 가지 효소들이 다량 요구되고 있는 실정이다. In particular, among the enzymatic methods, the types of enzymes that can be used include ginsenoside glycosidase, α-L-arabinopyranosidase, and α-L-arabinofuranosidase. It has been reported that enzymes such as (α-L-arabinofuranosidase) and α-L-rhamnosidase biotransform major ginsenosides such as Rb1, Rb2, Rc and Re. . That is, the saponins extracted from ginseng are mostly formed of complex saponins such as Rg1, Re, Rb1, Rb2, Rc and Rb3, so the number, type and location of sugars bound by glycosidic bonds are different. There is a situation in which a large amount of various enzymes are required.
본 발명의 목적은 자연상태의 인삼에 포함되어 있는 메이저 사포닌인 진세노사이드를 특정 아미노산 서열을 갖는 진세노사이드 글라이코시데이즈로 생물 전환하여 총 진세노사이드 함량이 현저히 높고, 총 진세노사이드 중 생리활성이 높은 마이너 사포닌의 함량이 높은 인삼 추출물을 유효성분으로 포함하는 염증성 질환의 치료, 개선 또는 예방용 진세노사이드 조성물을 제공하는 데 있다.It is an object of the present invention to bioconvert ginsenoside, a major saponin contained in natural ginseng, to ginsenoside glycosides having a specific amino acid sequence, so that the total ginsenoside content is remarkably high, among the total ginsenosides. It is to provide a ginsenoside composition for the treatment, improvement or prevention of inflammatory diseases comprising a ginseng extract having a high content of minor saponins having a high physiological activity as an active ingredient.
본 발명의 일 측면에 따르면,According to an aspect of the present invention,
총 진세노사이드 함량이 30 ~ 70중량% 함유되고, 상기 총 진세노사이드 중량에 대하여 Rg3 함량이 0.01 ~ 4중량% 함유된 인삼 추출물을 유효성분으로 포함하는 염증성 질환의 치료, 개선 또는 예방용 진세노사이드 조성물이 제공된다.Ginseng for the treatment, improvement or prevention of inflammatory diseases containing ginseng extract containing 30 to 70% by weight of total ginsenosides and 0.01 to 4% by weight of Rg3 content relative to the total ginsenosides weight as an active ingredient A cenoside composition is provided.
상기 진세노사이드 조성물은 총 진세노사이드 중량에 대하여 Gyp17, Rg3, C-Mc1, C-Mx1 및 F2 중에서 선택된 어느 하나가 2 내지 30중량% 함유된 것일 수 있다.The ginsenoside composition may contain 2 to 30% by weight of any one selected from Gyp17, Rg3, C-Mc1, C-Mx1 and F2 based on the total ginsenoside weight.
상기 진세노사이드 조성물은 총 진세노사이드 중량에 대하여 Gyp17, Rg3, C-Mc1, C-Mx1 및 F2의 중량의 합이 30 내지 80중량%인 것을 특징으로 한다.The ginsenoside composition is characterized in that the sum of the weights of Gyp17, Rg3, C-Mc1, C-Mx1 and F2 is 30 to 80% by weight based on the total ginsenoside weight.
상기 진세노사이드 조성물은 염증성 치료 또는 예방용 약학 조성물, 또는 염증성 질환 개선 또는 예방용 식품 조성물일 수 있다.The ginsenoside composition may be a pharmaceutical composition for treating or preventing inflammatory, or a food composition for improving or preventing inflammatory disease.
상기 염증성 질환은 염증성 피부질환, 크론병, 궤양성 대장염, 복막염, 골수염, 봉소염, 뇌막염, 뇌염, 췌장염, 외상 유발 쇼크, 기관지 천식, 알레르기성 비염, 낭포성 섬유증, 뇌졸중, 급성 기관지염, 만성 기관지염, 골관절염, 통풍, 척추관절병증, 강직성 척추염, 장질환 척추염, 연소자성 관절병증, 연소자성 강직성 척추염, 반응성 관절병증, 감염성 관절염, 전신성 홍반성 루푸스, 재귀열, 건선, 후-감염성 관절염, 임균성 관절염, 결핵성 관절염, 바이러스성 관절염, 진균성 관절염, 매독성 관절염, 류마티스성 다발성근육통, 관절 세포 동맥염, 칼슘 결정 침착 관절병증, 비-관절 류마티즘, 점액낭염, 건초염, 및 혈색소증 중에서 선택된 어느 하나일 수 있다.The inflammatory diseases include inflammatory skin disease, Crohn's disease, ulcerative colitis, peritonitis, osteomyelitis, cellulitis, meningitis, encephalitis, pancreatitis, trauma-induced shock, bronchial asthma, allergic rhinitis, cystic fibrosis, stroke, acute bronchitis, chronic bronchitis, Osteoarthritis, gout, spondyloarthropathy, ankylosing spondylitis, intestinal spondylitis, juvenile arthritis, juvenile ankylosing spondylitis, reactive arthritis, infectious arthritis, systemic lupus erythematosus, recursive fever, psoriasis, post-infectious arthritis, gonococcal arthritis, tuberculosis Arthritis, viral arthritis, fungal arthritis, syphilitic arthritis, rheumatoid polymyalgia, joint cell arteritis, calcium crystallization arthritis, non-articular rheumatism, bursitis, tendonitis, and hemoglobin.
본 발명의 다른 하나의 측면에 따르면,According to another aspect of the present invention,
(a) 인삼을 물, 탄소수 1-4의 저급 알코올, 또는 상기 저급 알코올과 물과의 혼합용매로 추출하여 인삼 추출물을 제조하는 단계; 및 (b) 상기 인삼 추출물을 서열번호 1의 아미노산 서열로 이루어진 진세노사이드 글라이코시데이즈로 효소 처리하는 단계;를 포함하는 인삼 추출물을 유효성분으로 포함하는 염증성 질환의 치료, 개선 또는 예방용 진세노사이드 조성물의 제조방법이 제공된다.(a) extracting ginseng with water, a lower alcohol having 1-4 carbon atoms, or a mixed solvent of the lower alcohol and water to prepare a ginseng extract; And (b) enzymatic treatment of the ginseng extract with ginsenoside glycosides consisting of the amino acid sequence of SEQ ID NO: 1; Jin for the treatment, improvement or prevention of inflammatory diseases comprising a ginseng extract as an active ingredient A method of preparing a cenoside composition is provided.
상기 효소 처리에 따라 진세노사이드 Re, Rb1, Rc, Rb2, Rb3 및 Rd 중에서 선택된 1종 이상이 Gyp17, Rg3, C-Mc1, C-Mx1 및 F2 중에서 선택된 1종 이상으로 전부 또는 부분적으로 생물전환 될 수 있다.According to the enzyme treatment, at least one selected from ginsenosides Re, Rb1, Rc, Rb2, Rb3 and Rd is all or partially bioconverted to at least one selected from Gyp17, Rg3, C-Mc1, C-Mx1 and F2. Can be.
본 발명의 인삼 추출물을 유효성분으로 포함하는 염증성 질환의 치료, 개선 또는 예방용 진세노사이드 조성물은 자연상태의 인삼에 포함되어 있는 메이저 사포닌인 진세노사이드를 특정 아미노산 서열을 갖는 진세노사이드 글라이코시데이즈로 생물 전환하여 총 진세노사이드 함량이 현저히 높고, 총 진세노사이드 중 마이너 사포닌 함량을 증가시켜 생리활성을 높여 항산화, 항염증, 항노화 기능성을 향상시킬 수 있다.The ginsenoside composition for the treatment, improvement or prevention of inflammatory diseases comprising the ginseng extract of the present invention as an active ingredient contains ginsenoside, a major saponin contained in natural ginseng, and ginsenoside glycosides having a specific amino acid sequence. By bioconversion to Sidase, the total ginsenoside content is remarkably high, and the physiological activity is increased by increasing the minor saponin content of the total ginsenosides, thereby improving antioxidant, anti-inflammatory, and anti-aging functions.
도 1은 진세노사이드 사이즈 마커들을 나타낸 것이다.
도 2는 반응 전 진세노사이드 성분을 나타낸 HPLC 분석결과이다.
도 3은 진세노사이드 글라이코시데이즈와 반응 후 진세노사이드 성분을 나타낸 HPLC 분석결과이다.
도 4는 실시예 1의 진세노사이드 조성물에 대한 세포 독성 시험 결과이다.
도 5는 실시예 1의 진세노사이드 조성물에 대한 TNF-α 발현 측정 시험 결과이다.
도 6은 실시예 1의 진세노사이드 조성물에 대한 IL-6 발현 측정 시험 결과이다.
도 7은 실시예 1의 진세노사이드 조성물에 대한 산화질소(nitric oxide, NO)의 생성 억제 측정 시험 결과이다.
도 8은 본 발명에 사용된 진세노사이드 글라이코시데이즈의 아미노산 서열이다.1 shows ginsenoside size markers.
2 is an HPLC analysis result showing the ginsenoside component before the reaction.
3 is an HPLC analysis result showing ginsenoside components after reaction with ginsenoside glycosides.
4 is a result of a cytotoxicity test for the ginsenoside composition of Example 1.
5 is a test result of TNF-α expression measurement for the ginsenoside composition of Example 1.
6 is an IL-6 expression measurement test result for the ginsenoside composition of Example 1.
7 is a measurement test result of the inhibition of production of nitric oxide (NO) for the ginsenoside composition of Example 1. FIG.
8 is an amino acid sequence of ginsenoside glycosidase used in the present invention.
본 발명은 다양한 변환을 가할 수 있고 여러 가지 실시예를 가질 수 있는 바, 특정 실시예들을 도면에 예시하고 상세한 설명에 상세하게 설명하고자 한다. 그러나, 이는 본 발명을 특정한 실시 형태에 대해 한정하려는 것이 아니며, 본 발명의 사상 및 기술 범위에 포함되는 모든 변환, 균등물 내지 대체물을 포함하는 것으로 이해되어야 한다. 본 발명을 설명함에 있어서 관련된 공지 기술에 대한 구체적인 설명이 본 발명의 요지를 흐릴 수 있다고 판단되는 경우 그 상세한 설명을 생략한다.Since the present invention can apply various transformations and have various embodiments, specific embodiments are illustrated in the drawings and will be described in detail in the detailed description. However, this is not intended to limit the present invention to a specific embodiment, it should be understood to include all conversions, equivalents, and substitutes included in the spirit and scope of the present invention. In describing the present invention, when it is determined that a detailed description of a related known technology may obscure the subject matter of the present invention, a detailed description thereof will be omitted.
이하, 본 발명의 염증성 질환의 치료, 개선 또는 예방용 진세노사이드 조성물에 대해 설명하도록 한다.Hereinafter, the ginsenoside composition for the treatment, improvement or prevention of inflammatory diseases of the present invention will be described.
본 발명의 진세노사이드 조성물은 총 진세노사이드 함량이 30 ~ 70중량% 함유되고, 상기 총 진세노사이드 중량에 대하여 Rg3 함량이 0.01 ~ 4중량% 함유된 인삼 추출물을 유효성분으로 포함하는 것을 특징으로 한다.The ginsenoside composition of the present invention comprises a ginseng extract containing a total ginsenoside content of 30 to 70% by weight, and an Rg3 content of 0.01 to 4% by weight based on the total ginsenoside weight as an active ingredient. It is done.
상기 진세노사이드 조성물은 총 진세노사이드 중량에 대하여 Gyp17, Rg3, C-Mc1, C-Mx1 및 F2 중에서 선택된 어느 하나가 2 내지 30중량% 함유된 것이 바람직하다.The ginsenoside composition preferably contains 2 to 30% by weight of any one selected from Gyp17, Rg3, C-Mc1, C-Mx1 and F2 based on the total ginsenoside weight.
상기 진세노사이드 조성물은 총 진세노사이드 중량에 대하여 Gyp17, Rg3, C-Mc1, C-Mx1 및 F2의 중량의 합이 30 내지 80중량%인 것이 바람직하다.In the ginsenoside composition, it is preferable that the sum of the weights of Gyp17, Rg3, C-Mc1, C-Mx1 and F2 is 30 to 80% by weight based on the total ginsenoside weight.
상기 진세노사이드 조성물은 염증성 질환 치료 또는 예방용 약학 조성물, 또는 염증성 질환 개선 또는 예방용 식품 조성물일 수 있다.The ginsenoside composition may be a pharmaceutical composition for treating or preventing inflammatory diseases, or a food composition for improving or preventing inflammatory diseases.
상기 염증성 질환은 염증성 피부질환, 크론병, 궤양성 대장염, 복막염, 골수염, 봉소염, 뇌막염, 뇌염, 췌장염, 외상 유발 쇼크, 기관지 천식, 알레르기성 비염, 낭포성 섬유증, 뇌졸중, 급성 기관지염, 만성 기관지염, 골관절염, 통풍, 척추관절병증, 강직성 척추염, 장질환 척추염, 연소자성 관절병증, 연소자성 강직성 척추염, 반응성 관절병증, 감염성 관절염, 전신성 홍반성 루푸스, 재귀열, 건선, 후-감염성 관절염, 임균성 관절염, 결핵성 관절염, 바이러스성 관절염, 진균성 관절염, 매독성 관절염, 류마티스성 다발성근육통, 관절 세포 동맥염, 칼슘 결정 침착 관절병증, 비-관절 류마티즘, 점액낭염, 건초염, 혈색소증 등일 수 있으나, 본 발명의 범위가 여기에 한정되지 않는다.The inflammatory diseases include inflammatory skin disease, Crohn's disease, ulcerative colitis, peritonitis, osteomyelitis, cellulitis, meningitis, encephalitis, pancreatitis, trauma-induced shock, bronchial asthma, allergic rhinitis, cystic fibrosis, stroke, acute bronchitis, chronic bronchitis, Osteoarthritis, gout, spondyloarthropathy, ankylosing spondylitis, intestinal spondylitis, juvenile arthritis, juvenile ankylosing spondylitis, reactive arthritis, infectious arthritis, systemic lupus erythematosus, recursive fever, psoriasis, post-infectious arthritis, gonococcal arthritis, tuberculosis Arthritis, viral arthritis, fungal arthritis, syphilitic arthritis, rheumatoid polymyalgia, joint cell arteritis, calcium crystallization arthritis, non-joint rheumatism, bursitis, tendonitis, hemoglobin, etc. Not limited.
이하, 본 발명의 염증성 질환의 치료, 개선 또는 예방용 진세노사이드 조성물의 제조방법에 대래 설명하도록 한다.Hereinafter, a method of preparing a ginsenoside composition for treating, improving or preventing inflammatory diseases according to the present invention will be described.
먼저, 인삼을 물, 탄소수 1-4의 저급 알코올, 또는 상기 저급 알코올과 물과의 혼합용매로 추출하여 인삼 추출물을 제조한다(단계 a). First, ginseng is extracted with water, a lower alcohol having 1-4 carbon atoms , or a mixed solvent of the lower alcohol and water to prepare a ginseng extract (step a).
본 발명에서 이용되는 추출용매는 물, 탄소수 1-4의 저급 알코올, 상기 저급 알코올과 물과의 혼합용매를 사용하는 것이 바람직하나, 본 발명의 범위가 여기에 한정되지 않으며, 아세톤, 에틸 아세테이트, 클로로포름, 부틸아세테이트, 1,3-부틸렌글리콜, 헥산, 디에틸에테르 등을 사용할 수도 있다.The extraction solvent used in the present invention is preferably water, a lower alcohol having 1-4 carbon atoms, and a mixed solvent of the lower alcohol and water, but the scope of the present invention is not limited thereto, and acetone, ethyl acetate, Chloroform, butyl acetate, 1,3-butylene glycol, hexane, diethyl ether, and the like can also be used.
본 명세서에서 사용되는 용어 ‘추출물’은 당업계에서 조추출물(crude extract)로 통용되는 의미를 갖지만, 광의적으로는 추출물을 추가적으로 분획(fractionation)한 분획물도 포함할 수 있다. 또한, 감압 증류 및 동결 건조, 또는 분무 건조 등과 같은 추가적인 과정에 의해 분말 상태로 제조될 수 있다.The term “extract” as used herein has a meaning commonly used as a crude extract in the art, but may include a fraction obtained by additionally fractionating the extract. Further, it may be prepared in a powder state by an additional process such as distillation under reduced pressure and freeze drying, or spray drying.
이후, 상기 인삼 추출물을 서열번호 1의 아미노산 서열로 이루어진 진세노사이드 글라이코시데이즈로 효소 처리한다(단계 b). Thereafter, the enzyme-treated ginseng extract in the jinse industrial grade articles lycopene during Days consisting of the amino acid sequence of SEQ ID NO: 1 (step b).
상기 진세노사이드 글라이코시데이즈의 아미노산 서열은 도 7에 나타낸 바와 같다.The amino acid sequence of the ginsenoside glycosidase is as shown in FIG. 7.
상기 효소 처리에 따라 진세노사이드 Re, Rb1, Rc, Rb2, Rb3 및 Rd 중에서 선택된 1종 이상이 Gyp17, Rg3, C-Mc1, C-Mx1 및 F2 중에서 선택된 1종 이상으로 전부 또는 부분적으로 생물전환 될 수 있다.According to the enzyme treatment, at least one selected from ginsenosides Re, Rb1, Rc, Rb2, Rb3 and Rd is all or partially bioconverted to at least one selected from Gyp17, Rg3, C-Mc1, C-Mx1 and F2. Can be.
이에 따라 인삼 추출물 내의 진세노사이드 함량이 3 내지 7배로 현저히 높아질 뿐 아니라, 총 진세노사이드 중 생리활성이 높은 마이너형 사포닌 즉 Gyp17, Rg3, C-Mc1, C-Mx1 및 F2이 생성됨으로써 항산화, 항염증, 항노화 기능성을 현저히 향상시킬 수 있다.Accordingly, the ginsenoside content in the ginseng extract is significantly increased by 3 to 7 times, as well as the generation of minor saponins having high physiological activity among the total ginsenosides, such as Gyp17, Rg3, C-Mc1, C-Mx1 and F2, and thereby antioxidant, Anti-inflammatory and anti-aging functions can be remarkably improved.
한편, 본 명세서에서 용어 ‘유효성분으로 포함하는’이란 진세노사이드 조성물의 효능 또는 활성을 달성하는 데 충분한 양을 포함하는 것을 의미한다. 본 발명의 한 구체예에서, 본 발명의 조성물 내에서 진세노사이드 조성물은 예를 들어, 0.001 mg/kg 이상, 바람직하게는 0.1 mg/kg 이상, 보다 바람직하게는 1 mg/kg 이상, 보다 더 바람직하게는 10 mg/kg 이상 포함된다. 진세노사이드 조성물은 천연물로서 과량 투여하여도 인체에 부작용이 없으므로 본 발명의 조성물 내에 포함되는 진세노사이드 조성물의 양적 상한은 당업자가 적절한 범위 내에서 선택하여 실시할 수 있다.Meanwhile, in the present specification, the term “including as an active ingredient” means including an amount sufficient to achieve the efficacy or activity of the ginsenoside composition. In one embodiment of the present invention, the ginsenoside composition in the composition of the present invention is, for example, 0.001 mg/kg or more, preferably 0.1 mg/kg or more, more preferably 1 mg/kg or more, even more. Preferably it contains 10 mg/kg or more. Since the ginsenoside composition is a natural product and does not have side effects on the human body even if it is administered in an excessive amount, the upper limit of the quantity of the ginsenoside composition included in the composition of the present invention can be selected and implemented within an appropriate range by a person skilled in the art.
본 발명의 약학 조성물은 상기 유효 성분 이외에 약학으로 적합하고 생리학적으로 허용되는 보조제를 사용하여 제조될 수 있으며, 상기 보조제로는 부형제, 붕해제, 감미제, 결합제, 피복제, 팽창제, 윤활제, 활택제 또는 향미제 등을 사용할 수 있다.In addition to the active ingredients, the pharmaceutical composition of the present invention may be prepared using a physiologically acceptable auxiliary agent, and the auxiliary agent includes an excipient, a disintegrant, a sweetener, a binder, a coating agent, an expanding agent, a lubricant, and a lubricant. Alternatively, flavoring agents and the like can be used.
상기 약학 조성물은 투여를 위해서 상기 기재한 유효 성분 이외에 추가로 약학으로 허용 가능한 담체를 1종 이상 포함하여 약학 조성물로 바람직하게 제제화할 수 있다.For administration, the pharmaceutical composition may contain one or more pharmaceutically acceptable carriers in addition to the above-described active ingredients, and may be preferably formulated into a pharmaceutical composition.
상기 약학 조성물의 제제 형태는 과립제, 산제, 정제, 피복정, 캡슐제, 좌제, 액제, 시럽, 즙, 현탁제, 유제, 점적제 또는 주사 가능한 액제 등이 될 수 있다. 예를 들어, 정제 또는 캡슐제의 형태로의 제제화를 위해, 유효 성분은 에탄올, 글리세롤, 물 등과 같은 경구, 무독성의 약학으로 허용 가능한 불활성 담체와 결합될 수 있다. 또한, 원하거나 필요한 경우, 적합한 결합제, 윤활제, 붕해제 및 발색제 또한 혼합물로 포함될 수 있다. 적합한 결합제는 이에 제한되는 것은 아니나, 녹말, 젤라틴, 글루코스 또는 베타-락토오스와 같은 천연 당, 옥수수 감미제, 아카시아, 트래커캔스 또는 소듐올레이트와 같은 천연 및 합성 검, 소듐 스테아레이트, 마그네슘 스테아레이트, 소듐 벤조에이트, 소듐 아세테이트, 소듐 클로라이드 등을 포함한다. 붕해제는 이에 제한되는 것은 아니나, 녹말, 메틸 셀룰로스, 아가, 벤토니트, 잔탄 검 등을 포함한다.The formulation form of the pharmaceutical composition may be granules, powders, tablets, coated tablets, capsules, suppositories, solutions, syrups, juices, suspensions, emulsions, drops, or injectable solutions. For example, for formulation in the form of tablets or capsules, the active ingredient may be combined with an oral, non-toxic pharmaceutically acceptable inert carrier such as ethanol, glycerol, water, and the like. In addition, if desired or necessary, suitable binders, lubricants, disintegrants and coloring agents may also be included in the mixture. Suitable binders are, but are not limited to, natural sugars such as starch, gelatin, glucose or beta-lactose, corn sweeteners, natural and synthetic gums such as acacia, trackcacanth or sodium oleate, sodium stearate, magnesium stearate, sodium Benzoate, sodium acetate, sodium chloride, and the like. Disintegrants include, but are not limited to, starch, methyl cellulose, agar, bentonite, xanthan gum, and the like.
액상 용액으로 제제화되는 조성물에 있어서 허용 가능한 약학 담체로는, 멸균 및 생체에 적합한 것으로서, 식염수, 멸균수, 링거액, 완충 식염수, 알부민 주사용액, 덱스트로즈 용액, 말토 덱스트린 용액, 글리세롤, 에탄올 및 이들 성분 중 1 성분 이상을 혼합하여 사용할 수 있으며, 필요에 따라 항산화제, 완충액, 정균제 등 다른 통상의 첨가제를 첨가할 수 있다. 또한 희석제, 분산제, 계면활성제, 결합제 및 윤활제를 부가적으로 첨가하여 수용액, 현탁액, 유탁액 등과 같은 주사용 제형, 환약, 캡슐, 과립 또는 정제로 제제화할 수 있다.As acceptable pharmaceutical carriers for compositions formulated as liquid solutions, sterilization and biocompatible solutions, saline, sterile water, Ringer's solution, buffered saline, albumin injection solution, dextrose solution, maltodextrin solution, glycerol, ethanol, and these One or more of the components may be mixed and used, and other conventional additives such as antioxidants, buffers, and bacteriostatic agents may be added as necessary. In addition, diluents, dispersants, surfactants, binders, and lubricants may be additionally added to prepare injection formulations such as aqueous solutions, suspensions, emulsions, etc., pills, capsules, granules, or tablets.
본 발명의 약학 조성물은 경구 또는 비경구로 투여할 수 있고, 비경구 투여인 경우에는 정맥 내 주입, 피하 주입, 근육 주입, 복강 주입, 경피 투여 등으로 투여할 수 있으며, 바람직하게는 경구 투여이다.The pharmaceutical composition of the present invention may be administered orally or parenterally, and in the case of parenteral administration, it may be administered by intravenous injection, subcutaneous injection, intramuscular injection, intraperitoneal injection, transdermal administration, etc., preferably oral administration.
본 발명의 약학 조성물의 적합한 투여량은 제제화 방법, 투여 방식, 환자의 연령, 체중, 성, 병적 상태, 음식, 투여 시간, 투여 경로, 배설 속도 및 반응 감응성과 같은 요인들에 의해 다양하며, 보통으로 숙련된 의사는 소망하는 치료 또는 예방에 효과적인 투여량을 용이하게 결정 및 처방할 수 있다. 본 발명의 바람직한 구현 예에 따르면, 본 발명의 약학 조성물의 1일 투여량은 0.0001-10 g/㎏이다.A suitable dosage of the pharmaceutical composition of the present invention varies depending on factors such as formulation method, mode of administration, age, weight, sex, pathological condition, food, administration time, route of administration, excretion rate and response sensitivity of the patient, and is usually As such, a skilled physician can easily determine and prescribe an effective dosage for the desired treatment or prophylaxis. According to a preferred embodiment of the present invention, the daily dosage of the pharmaceutical composition of the present invention is 0.0001-10 g/kg.
본 발명의 약학 조성물은 당해 발명이 속하는 기술분야에서 통상의 지식을 가진 자가 용이하게 실시할 수 있는 방법에 따라, 약학으로 허용되는 담체 및/또는 부형제를 이용하여 제제화 함으로써 단위 용량 형태로 제조되거나 또는 다용량 용기 내에 내입시켜 제조될 수 있다. 이때 제형은 오일 또는 수성 매질중의 용액, 현탁액 또는 유화액 형태이거나 엑스제, 분말제, 과립제, 정제 또는 캅셀제 형태일 수도 있으며, 분산제 또는 안정화제를 추가적으로 포함할 수 있다.The pharmaceutical composition of the present invention is prepared in unit dosage form by formulating using a pharmaceutically acceptable carrier and/or excipient according to a method that can be easily carried out by a person skilled in the art, or It can be manufactured by being enclosed in a multi-volume container. In this case, the formulation may be in the form of a solution, suspension or emulsion in an oil or aqueous medium, or may be in the form of an extract, powder, granule, tablet or capsule, and may additionally include a dispersant or a stabilizer.
본 발명에 따른 식품 조성물은 기능성 식품으로 이용하거나, 각종 식품에 첨가할 수 있다. 본 발명의 조성물을 첨가할 수 있는 식품으로는 예를 들어, 음료류, 알코올 음료류, 과자류, 다이어트바, 유제품, 육류, 초코렛, 피자, 빵류 라면, 기타 면류, 껌류, 아이스크림류, 비타민 복합제, 건강보조식품류 등이 있다.The food composition according to the present invention can be used as a functional food or added to various foods. Foods to which the composition of the present invention can be added include, for example, beverages, alcoholic beverages, confectionery, diet bars, dairy products, meat, chocolate, pizza, ramen noodles, other noodles, gums, ice creams, vitamin complexes, health supplements. There are foods.
본 발명의 식품 조성물은 유효성분으로서 진세노사이드 조성물 뿐만 아니라, 식품 제조 시에 통상적으로 첨가되는 성분을 포함할 수 있으며, 예를 들어, 단백질, 탄수화물, 지방, 영양소, 조미제 및 향미제를 포함한다. 상술한 탄수화물의 예는 모노사카라이드, 예를 들어, 포도당, 과당 등; 디사카라이드, 예를 들어 말토스, 슈크로스, 올리고당 등; 및 폴리사카라이드, 예를 들어 덱스트린, 사이클로덱스트린 등과 같은 통상적인 당 및 자일리톨, 소르비톨, 에리트리톨 등의 당알콜이다. 향미제로서 천연 향미제 [타우마틴, 스테비아 추출물 (예를 들어 레바우디오시드 A, 글리시르히진 등]) 및 합성 향미제(사카린, 아스파르탐 등)를 사용할 수 있다. 예컨대, 본 발명의 식품 조성물이 드링크제와 음료류로 제조되는 경우에는 진세노사이드 조성물 이외에 구연산, 액상과당, 설탕, 포도당, 초산, 사과산, 과즙, 및 각종 식물 추출액 등을 추가로 포함시킬 수 있다.The food composition of the present invention may include a ginsenoside composition as an active ingredient, as well as an ingredient commonly added during food production, and, for example, include proteins, carbohydrates, fats, nutrients, flavoring agents, and flavoring agents. do. Examples of the aforementioned carbohydrates include monosaccharides such as glucose, fructose, and the like; Disaccharides such as maltose, sucrose, oligosaccharides, and the like; And polysaccharides, for example, common sugars such as dextrin and cyclodextrin, and sugar alcohols such as xylitol, sorbitol, and erythritol. As flavoring agents, natural flavoring agents [taumatin, stevia extract (eg, rebaudioside A, glycyrrhizin, etc.]) and synthetic flavoring agents (saccharin, aspartame, etc.) can be used. For example, when the food composition of the present invention is made of drinks and beverages, in addition to the ginsenoside composition, citric acid, liquid fructose, sugar, glucose, acetic acid, malic acid, fruit juice, and various plant extracts may be further included.
*본 발명은 진세노사이드 조성물을 유효성분으로 포함하는 건강기능식품을 제공한다. 건강기능식품이란, 진세노사이드 조성물을 음료, 차류, 향신료, 껌, 과자류 등의 식품소재에 첨가하거나, 캡슐화, 분말화, 현탁액 등으로 제조한 식품으로, 이를 섭취할 경우 건강상 특정한 효과를 가져오는 것을 의미하나, 일반 약품과는 달리 식품을 원료로 하여 약품의 장기 복용 시 발생할 수 있는 부작용 등이 없는 장점이 있다. 이와 같이 하여 얻어지는 본 발명의 건강기능식품은, 일상적으로 섭취하는 것이 가능하기 때문에 매우 유용하다. 이와 같은 건강기능식품에 있어서의 진세노사이드 조성물의 첨가량은, 대상인 건강기능식품의 종류에 따라 달라 일률적으로 규정할 수 없지만, 식품 본래의 맛을 손상시키지 않는 범위에서 첨가하면 되며, 대상 식품에 대하여 통상 0.01 내지 50 중량%, 바람직하기로는 0.1 내지 20 중량%의 범위이다. 또한, 환제, 과립제, 정제 또는 캡슐제 형태의 건강기능식품의 경우에는 통상 0.1 내지 100 중량% 바람직하기로는 0.5 내지 80 중량%의 범위에서 첨가하면 된다. 한 구체예에서, 본 발명의 건강기능식품은 환제, 정제, 캡슐제 또는 음료의 형태일 수 있다.* The present invention provides a health functional food comprising a ginsenoside composition as an active ingredient. Health functional foods are foods prepared by adding a ginsenoside composition to food materials such as beverages, teas, spices, chewing gums, confectionery, or encapsulating, powdering, and suspending, and when ingested, they have a specific effect on health. It means coming, but unlike general drugs, it has the advantage of not having side effects that may occur when taking the drug for a long time by using food as a raw material. The health functional food of the present invention obtained in this way is very useful because it can be consumed on a daily basis. The amount of ginsenoside composition added in such health functional foods cannot be uniformly regulated depending on the type of health functional food to be targeted, but can be added within the range that does not damage the original taste of the food. It is usually in the range of 0.01 to 50% by weight, preferably 0.1 to 20% by weight. In addition, in the case of health functional foods in the form of pills, granules, tablets or capsules, it is usually added in the range of 0.1 to 100% by weight, preferably 0.5 to 80% by weight. In one embodiment, the health functional food of the present invention may be in the form of a pill, tablet, capsule or beverage.
[실시예][Example]
실시예Example 1: One: 진세노사이드Ginsenoside 생물전환 Biotransformation
인삼은 홍미삼을 구입(대동고려삼, 대한민국)하여 에탄올을 이용하여 사포닌을 추출하였다. 추출한 사포닌은 3차 정제수를 이용하여 용해하였으며, 반응은 50 mM 포스페이트 버퍼 (phosphate buffer, pH 7.0) 용액 속에 서열번호 1의 아미노산 서열로 이루어진 진세노사이드 글라이코시데이즈:기질 = 1:4,000 (몰비, Molar Ratio) 비로 첨가하여 37 ℃ 쉐이킹 인큐베이터(shaking incubator)에서 하루 동안 실시하였다. 반응 완료 후 로타리 이베퍼레이터(rotary evaporator, R300, BUCHI)를 이용하여 최초 반응 용량 대비 30~50 %로 농축하였다. 농축물은 다시 동량의 n-부탄올을 첨가하여 혼합하고 원심분리기를 이용하여 원심 분리하고, 상청액만을 별도 분리하여 저온 진공상태에서 원심분리에 의해 용매를 기화시켰다 (Speed Vac. Drying). 건조된 반응물들은 믹서기(Mixer)를 이용하여 분말화하였으며 분말화 후 60℃ 건조기에서 48시간 동안 별도로 건조하였다. For ginseng, red rice ginseng was purchased (Daedong Korea Ginseng, Korea) and saponin was extracted using ethanol. The extracted saponin was dissolved using tertiary purified water, and the reaction was ginsenoside glycosidase consisting of the amino acid sequence of SEQ ID NO: 1 in a 50 mM phosphate buffer (pH 7.0) solution: substrate = 1: 4,000 (molar ratio , Molar Ratio) was added at a ratio and carried out for one day in a shaking incubator at 37°C. After completion of the reaction, it was concentrated to 30-50% of the initial reaction volume using a rotary evaporator (R300, BUCHI). The concentrate was mixed with the same amount of n-butanol again, and then centrifuged using a centrifuge. Only the supernatant was separated and the solvent was evaporated by centrifugation in a low-temperature vacuum state (Speed Vac. Drying). The dried reactants were powdered using a mixer, and after powdering, they were separately dried in a dryer at 60° C. for 48 hours.
[시험예][Test Example]
시험예Test example 1: 생물전환 확인 1: Confirmation of biotransformation
실시예 1에 따라 별도로 건조한 반응물은 HPLC (High Performance Liquid Chromatography)를 이용하여 조성물 분석하였다. 도 1은 진세노사이드 사이즈 마커들을 나타낸 것이다. 또한, 상기 진세노사이드 글라이코시데이즈와 반응 전의 진세노사이드 성분을 아래의 표 1과 도 2에 나타내었으며, 진세노사이드 글라이코시데이즈와 반응 후의 진세노사이드 성분을 아래의 표 2와 도 3에 나타내었다.Separately dried reactants according to Example 1 were analyzed for the composition using High Performance Liquid Chromatography (HPLC). 1 shows ginsenoside size markers. In addition, the ginsenoside components before the reaction with ginsenoside glycosides are shown in Tables 1 and 2 below, and the ginsenoside components after the reaction with ginsenoside glycosides are shown in Table 2 below. It is shown in 3.
이에 따르면, 인삼 추출물 내의 진세노사이드 함량이 11.65%에서 47.96%로 4배 이상 증가하였을 뿐 아니라, 진세노사이드의 조성을 살펴보면, 메이저 사포닌으로부터 마이너 사포닌인 Gyp17, Rg3, C-Mc1, C-Mx1 및 F2로 생물전환이 이루어져 진세노사이드의 성분이 크게 변화하였음을 확인할 수 있다.According to this, the ginsenoside content in the ginseng extract increased more than four times from 11.65% to 47.96%, and looking at the composition of ginsenosides, minor saponins Gyp17, Rg3, C-Mc1, C-Mx1 and It can be seen that the composition of ginsenosides changed significantly due to biotransformation to F2.
시험예Test example 2: 2: 진세노사이드Ginsenoside 효능 시험 Efficacy test
실시예 2에 따라 제조된 사포닌 시료를 이용하여 항산화, 항염증 및 항노화 효능에 관한 시험관 내(in vitro) 실험을 진행하였다.Using the saponin sample prepared according to Example 2, in vitro (in vitro ) experiments were carried out.
(1) 세포 독성(Cytotoxicity) 시험(1) Cytotoxicity test
대식세포 RAW264.7에 LPS(lipopolysaccharide)를 1㎍/㎖ 처리한 것과 처리하지 않은 것을 각각 96-웰 플레이트에 1×104개 세포/웰이 되도록 분주하여 8시간 동안 배양하였다. 배양 후 새로운 배양액(10% FBS(fetal bovine serum)와 1% 페니실린(penicillin)이 함유되어 있는 DMEM(Eagle's minimal essential medium) 배지)으로 교체하고, 실시예 1의 진세노사이드 조성물을 각각 1.3, 2.5, 5, 10㎍/㎖로 처리하고 24시간 동안 배양하였다. 배양 후 각 웰에 10㎕의 WST 용액을 첨가한 후 세포 배양기에서 30분간 반응 시킨 후 450㎚에서 흡광도의 변화를 측정하여 대조군에 대한 세포 생존율을 백분율로 표시하였고, 그 결과를 도 4에 나타내었다. 이에 따르면, 실시예 1의 진세노사이드 복합체의 처리에 의해 세포 생존율이 높아지므로 세포 독성은 없는 것으로 확인되었다.Macrophage RAW264.7 treated with 1 μg/ml of LPS (lipopolysaccharide) and untreated were dispensed into a 96-well plate at 1×10 4 cells/well, and cultured for 8 hours. After incubation, a new culture solution (Eagle's minimal essential medium (DMEM) medium containing 10% FBS (fetal bovine serum) and 1% penicillin) was replaced, and the ginsenoside composition of Example 1 was 1.3 and 2.5, respectively. , 5, 10 ㎍ / ㎖ and incubated for 24 hours. After incubation, 10 µl of WST solution was added to each well, and then reacted for 30 minutes in a cell incubator, and the change in absorbance at 450 nm was measured to indicate the cell viability relative to the control as a percentage, and the results are shown in FIG. 4. . According to this, it was confirmed that there was no cytotoxicity because the cell viability was increased by the treatment of the ginsenoside complex of Example 1.
(2) TNF-α 발현 측정(2) TNF-α expression measurement
상기 방법과 동일하게 LPS를 처리 또는 무처리한 RAW264.7 세포를 배양하고, 배양액과 세포를 1㎖ 튜브에 넣고 원심 분리한 후, 상청액을 수득하고 루미넥스(luminex) 키트를 통해 TNF-α의 양을 측정하고 그 결과를 도 5에 나타내었다. 이에 따르면, 진세노사이드 복합체의 처리량이 증가할수록 TNF-α의 생성이 감소하는 것으로 나타났다.In the same manner as in the above method, RAW264.7 cells treated with or without LPS were cultured, and the culture medium and cells were placed in a 1 ml tube and centrifuged. Then, a supernatant was obtained and TNF-α was The amount was measured and the results are shown in FIG. 5. According to this, it was found that the production of TNF-α decreased as the throughput of the ginsenoside complex increased.
(3) IL-6 발현 측정(3) IL-6 expression measurement
TNF-α 발현 측정과 동일한 방법으로 IL-6 발현을 측정하여 그 결과를 도 6에 나타내었다. 이에 따르면, 진세노사이드 복합체의 처리량이 1.3 ㎍/㎖인 것부터 IL-6의 생성이 크게 감소하는 것으로 나타났다.IL-6 expression was measured by the same method as TNF-α expression measurement, and the results are shown in FIG. 6. According to this, it was found that the production of IL-6 was significantly reduced from 1.3 µg/ml of the ginsenoside complex.
(4) 산화질소(nitric oxide, NO)의 생성 억제 측정(4) Measurement of inhibition of formation of nitric oxide (NO)
상기 방법과 동일하게 얻은 배양액을 NO 검출 키트(Nitric oxide detection kit, Intron Biotechnology, Korea)를 이용하여 산화질소 생성을 측정하여 그 결과를 도 7에 나타내었다. 이에 따르면, 실시예 1의 진세노사이드 조성물의 처리량에 의존적으로 산화질소의 생성량이 감소하였으므로 항염증 효능이 우수함을 확인할 수 있었다.The culture solution obtained in the same manner as the above method was measured for nitric oxide production using a NO detection kit (Intron Biotechnology, Korea), and the results are shown in FIG. 7. According to this, it was confirmed that the amount of nitric oxide produced was reduced depending on the treatment amount of the ginsenoside composition of Example 1, so that the anti-inflammatory effect was excellent.
이상, 본 발명의 실시예들에 대하여 설명하였으나, 해당 기술 분야에서 통상의 지식을 가진 자라면 특허청구범위에 기재된 본 발명의 사상으로부터 벗어나지 않는 범위 내에서, 구성 요소의 부가, 변경, 삭제 또는 추가 등에 의해 본 발명을 다양하게 수정 및 변경시킬 수 있을 것이며, 이 또한 본 발명의 권리범위 내에 포함된다고 할 것이다.In the above, the embodiments of the present invention have been described, but those of ordinary skill in the art will add, change, delete or add components within the scope not departing from the spirit of the present invention described in the claims. Various modifications and changes can be made to the present invention by means of the like, and it will be said that this is also included within the scope of the present invention.
<110> BEESEN Bio. Co., Ltd. <120> GINSENOSIDE COMPOSITION FOR TREATING, IMPROVING, OR PREVENTING INFLAMMATORY DISEASE, AND METHOD FOR PREPARING THE SAME <130> HPC-7597 <160> 1 <170> KoPatentIn 3.0 <210> 1 <211> 421 <212> PRT <213> Artificial Sequence <220> <223> 6MT BGL167 <400> 1 Thr Pro Met Thr Asn Pro Phe Pro Gln Asp Phe Leu Trp Gly Val Ala 1 5 10 15 Thr Ala Gly His Gln Val Glu Gly Asn Asn Val Asn Ser Asp Val Trp 20 25 30 Phe Leu Glu His Leu Pro Gly Thr Ile Phe Ala Glu Pro Ser Gly Asp 35 40 45 Ala Val Asp His Tyr His Arg Tyr Arg Glu Asp Ile Ala Leu Ile Ala 50 55 60 Gly Leu Gly Phe Thr Ser Tyr Arg Phe Ser Val Glu Trp Ala Arg Ile 65 70 75 80 Glu Pro Glu Glu Gly His Phe Ser Val Ala Ala Leu Asp His Tyr Lys 85 90 95 Arg Val Leu Glu Ala Cys Arg Glu His Gly Leu Thr Pro Val Val Thr 100 105 110 Phe His His Phe Ala Ser Pro Leu Trp Leu Leu Arg Ser Gly Gly Trp 115 120 125 Glu Gly Glu Arg Thr Pro Glu Leu Phe Ala Arg Tyr Cys Gly Arg Val 130 135 140 Met Ala His Leu Gly Asp Leu Ile Gly Val Ala Cys Thr Leu Asn Glu 145 150 155 160 Pro Asn Leu Pro Trp Leu Leu Glu Ser Phe Gly Ala Gly Gly Glu Ala 165 170 175 Pro Glu Asn Arg Gly Lys Val Pro Met Trp Ala Ala Ala Ala Gln Arg 180 185 190 Leu Gly Val Asp Ala Ser Thr Val Ala Pro Phe Trp Phe Cys Ser Thr 195 200 205 Glu Ala Gly Phe Asn Val Lys Leu Ala Ala His Lys Ala Ala Thr Glu 210 215 220 Ala Ile Lys Ala Trp Arg Pro Asp Leu Arg Val Gly Trp Thr Leu Ala 225 230 235 240 Asn Ser Asp Ile Gln Ser Val Pro Gly Gly Glu Glu Ile Ala Ala Gln 245 250 255 Val Arg Arg Asp Val Asn Glu Arg Phe Leu Glu Ala Ser Arg Gly Asp 260 265 270 Asp Phe Val Gly Ile Gln Thr Tyr Gly Arg Thr Val Tyr Gly Pro Asp 275 280 285 Gly His Ala Pro Ala Pro Glu Gly Val Ala Val Asn Gln Met Gly Trp 290 295 300 Glu Ile Tyr Pro Gln Ala Leu Glu Ala Thr Ile Arg Glu Ala Trp Arg 305 310 315 320 Val Ala Gly Ile Pro Val Met Val Thr Glu Asn Gly Leu Ala Thr Glu 325 330 335 Asp Asp Thr Gln Arg Val Ala Tyr Leu Arg Thr Ala Val Asp Gly Val 340 345 350 Ala Ser Cys Leu Ala Asp Gly Ile Asp Val Arg Gly Tyr Ile Ala Trp 355 360 365 Thr Ala Phe Asp Asn Phe Glu Trp Ala Ala Gly Tyr Gly Pro Lys Phe 370 375 380 Gly Leu Ile Ala Val Asp Arg Ser Thr Gln Glu Arg Thr Pro Lys Glu 385 390 395 400 Ser Ala Arg Trp Leu Gly Asn Phe Ala Arg Gln Gln Ala Pro Ala Glu 405 410 415 Ala Pro Gln Pro Ala 420 <110> BEESEN Bio. Co., Ltd. <120> GINSENOSIDE COMPOSITION FOR TREATING, IMPROVING, OR PREVENTING INFLAMMATORY DISEASE, AND METHOD FOR PREPARING THE SAME <130> HPC-7597 <160> 1 <170> KoPatentIn 3.0 <210> 1 <211> 421 <212> PRT <213> Artificial Sequence <220> <223> 6MT BGL167 <400> 1 Thr Pro Met Thr Asn Pro Phe Pro Gln Asp Phe Leu Trp Gly Val Ala 1 5 10 15 Thr Ala Gly His Gln Val Glu Gly Asn Asn Val Asn Ser Asp Val Trp 20 25 30 Phe Leu Glu His Leu Pro Gly Thr Ile Phe Ala Glu Pro Ser Gly Asp 35 40 45 Ala Val Asp His Tyr His Arg Tyr Arg Glu Asp Ile Ala Leu Ile Ala 50 55 60 Gly Leu Gly Phe Thr Ser Tyr Arg Phe Ser Val Glu Trp Ala Arg Ile 65 70 75 80 Glu Pro Glu Glu Gly His Phe Ser Val Ala Ala Leu Asp His Tyr Lys 85 90 95 Arg Val Leu Glu Ala Cys Arg Glu His Gly Leu Thr Pro Val Val Thr 100 105 110 Phe His His Phe Ala Ser Pro Leu Trp Leu Leu Arg Ser Gly Gly Trp 115 120 125 Glu Gly Glu Arg Thr Pro Glu Leu Phe Ala Arg Tyr Cys Gly Arg Val 130 135 140 Met Ala His Leu Gly Asp Leu Ile Gly Val Ala Cys Thr Leu Asn Glu 145 150 155 160 Pro Asn Leu Pro Trp Leu Leu Glu Ser Phe Gly Ala Gly Gly Glu Ala 165 170 175 Pro Glu Asn Arg Gly Lys Val Pro Met Trp Ala Ala Ala Ala Gln Arg 180 185 190 Leu Gly Val Asp Ala Ser Thr Val Ala Pro Phe Trp Phe Cys Ser Thr 195 200 205 Glu Ala Gly Phe Asn Val Lys Leu Ala Ala His Lys Ala Ala Thr Glu 210 215 220 Ala Ile Lys Ala Trp Arg Pro Asp Leu Arg Val Gly Trp Thr Leu Ala 225 230 235 240 Asn Ser Asp Ile Gln Ser Val Pro Gly Gly Glu Glu Ile Ala Ala Gln 245 250 255 Val Arg Arg Asp Val Asn Glu Arg Phe Leu Glu Ala Ser Arg Gly Asp 260 265 270 Asp Phe Val Gly Ile Gln Thr Tyr Gly Arg Thr Val Tyr Gly Pro Asp 275 280 285 Gly His Ala Pro Ala Pro Glu Gly Val Ala Val Asn Gln Met Gly Trp 290 295 300 Glu Ile Tyr Pro Gln Ala Leu Glu Ala Thr Ile Arg Glu Ala Trp Arg 305 310 315 320 Val Ala Gly Ile Pro Val Met Val Thr Glu Asn Gly Leu Ala Thr Glu 325 330 335 Asp Asp Thr Gln Arg Val Ala Tyr Leu Arg Thr Ala Val Asp Gly Val 340 345 350 Ala Ser Cys Leu Ala Asp Gly Ile Asp Val Arg Gly Tyr Ile Ala Trp 355 360 365 Thr Ala Phe Asp Asn Phe Glu Trp Ala Ala Gly Tyr Gly Pro Lys Phe 370 375 380 Gly Leu Ile Ala Val Asp Arg Ser Thr Gln Glu Arg Thr Pro Lys Glu 385 390 395 400 Ser Ala Arg Trp Leu Gly Asn Phe Ala Arg Gln Gln Ala Pro Ala Glu 405 410 415 Ala Pro Gln Pro Ala 420
Claims (6)
상기 인삼 추출물은 진세노사이드인 Gyp17, Rg3, C-Mc1, C-Mx1 및 F2을 포함하고,
상기 인삼 추출물의 총 진세노사이드 함량이 30 ~ 70중량%이고, 상기 총 진세노사이드 중량에 대하여 Gyp17, Rg3, C-Mc1, C-Mx1 및 F2 각각의 함량이 2 내지 30중량%인 인삼 추출물을 유효성분으로 포함하는 염증성 질환의 치료, 개선 또는 예방용 진세노사이드 조성물.The ginseng extract is an enzyme-treated ginsenoside glycosidase consisting of the amino acid sequence of SEQ ID NO: 1,
The ginseng extract comprises ginsenosides Gyp17, Rg3, C-Mc1, C-Mx1 and F2,
Wherein the ginseng extract has a total ginsenoside content of 30 to 70 wt% and a content of each of Gyp17, Rg3, C-Mc1, C-Mx1 and F2 is 2 to 30 wt% based on the total ginsenoside weight As an active ingredient, a ginsenoside composition for the treatment, improvement or prevention of an inflammatory disease.
상기 진세노사이드 조성물은 총 진세노사이드 중량에 대하여 Gyp17, Rg3, C-Mc1, C-Mx1 및 F2의 중량의 합이 30 내지 80중량%인 것을 특징으로 하는 인삼 추출물을 유효성분으로 포함하는 염증성 질환의 치료, 개선 또는 예방용 진세노사이드 조성물.The method according to claim 1,
The ginsenoside composition according to claim 1, wherein the sum of the weights of Gyp17, Rg3, C-Mc1, C-Mx1 and F2 is 30 to 80% by weight based on the total ginsenoside weight. A ginsenoside composition for the treatment, improvement or prevention of diseases.
상기 진세노사이드 조성물은 염증성 질환 치료 또는 예방용 약학 조성물인 것을 특징으로 하는 인삼 추출물을 유효성분으로 포함하는 진세노사이드 조성물.The method according to claim 1,
Wherein the ginsenoside composition is a pharmaceutical composition for the treatment or prevention of an inflammatory disease, comprising a ginsenoside extract as an active ingredient.
상기 진세노사이드 조성물은 염증성 질환 개선 또는 예방용 식품 조성물인 것을 특징으로 하는 인삼 추출물을 유효성분으로 포함하는 진세노사이드 조성물.The method according to claim 1,
Wherein the ginsenoside composition is a food composition for improving or preventing an inflammatory disease, comprising a ginsenoside extract as an active ingredient.
상기 염증성 질환은 염증성 피부질환, 크론병, 궤양성 대장염, 복막염, 골수염, 봉소염, 뇌막염, 뇌염, 췌장염, 외상 유발 쇼크, 기관지 천식, 알레르기성 비염, 낭포성 섬유증, 뇌졸중, 급성 기관지염, 만성 기관지염, 골관절염, 통풍, 척추관절병증, 강직성 척추염, 장질환 척추염, 연소자성 관절병증, 연소자성 강직성 척추염, 반응성 관절병증, 감염성 관절염, 전신성 홍반성 루푸스, 재귀열, 건선, 후-감염성 관절염, 임균성 관절염, 결핵성 관절염, 바이러스성 관절염, 진균성 관절염, 매독성 관절염, 류마티스성 다발성근육통, 관절 세포 동맥염, 칼슘 결정 침착 관절병증, 비-관절 류마티즘, 점액낭염, 건초염, 및 혈색소증 중에서 선택된 어느 하나인 것을 특징으로 하는 인삼 추출물을 유효성분으로 포함하는 염증성 질환의 치료, 개선 또는 예방용 진세노사이드 조성물.The method according to claim 1,
Wherein said inflammatory disease is selected from the group consisting of inflammatory skin diseases, Crohn's disease, ulcerative colitis, peritonitis, osteomyelitis, meningitis, meningitis, encephalitis, pancreatitis, trauma-induced shock, bronchial asthma, allergic rhinitis, cystic fibrosis, stroke, acute bronchitis, Osteoarthritis, gouty arthritis, systemic lupus erythematosus, recurrent fever, psoriasis, post-infectious arthritis, gonococcal arthritis, tuberculosis, osteoarthritis, osteoarthritis, gout, spondyloarthropathies, ankylosing spondylitis, Wherein the composition is any one selected from the group consisting of arthritis, viral arthritis, fungal arthritis, rheumatoid arthritis, rheumatoid multiple myalgia, arthropathic arthritis, calcium crystalloid arthropathy, non-articular rheumatism, bursitis, For the Treatment, Improvement or Prevention of Inflammatory Diseases Containing Extracts as Active Ingredients Side composition.
(b) 상기 인삼 추출물을 서열번호 1의 아미노산 서열로 이루어진 진세노사이드 글라이코시데이즈(ginsenoside glycosidase)로 효소 처리하는 단계;를 포함하고,
상기 효소 처리에 따라 진세노사이드 Re, Rb1, Rc, Rb2, Rb3 및 Rd 중에서 선택된 1종 이상이 Gyp17, Rg3, C-Mc1, C-Mx1 및 F2로 부분적으로 생물전환되는 것을 특징으로 하는 인삼 추출물을 유효성분으로 포함하는 염증성 질환의 치료, 개선 또는 예방용 진세노사이드 조성물의 제조방법.
(a) preparing ginseng extract by extracting ginseng with water, a lower alcohol having 1-4 carbon atoms, or a mixed solvent of the lower alcohol and water; And
(b) enzymatically treating the ginseng extract with ginsenoside glycosidase comprising the amino acid sequence of SEQ ID NO: 1,
Wherein at least one selected from ginsenosides Re, Rb1, Rc, Rb2, Rb3 and Rd is partially biotransformed into Gyp17, Rg3, C-Mc1, C-Mx1 and F2 according to the enzyme treatment. Or a pharmaceutically acceptable salt thereof, as an active ingredient, for the treatment, amelioration or prevention of an inflammatory disease.
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