KR100926798B1 - Antioxidant composition containing hispidin derivatives from the culture broth of fungi Phellinus and Inonotus spp. - Google Patents
Antioxidant composition containing hispidin derivatives from the culture broth of fungi Phellinus and Inonotus spp. Download PDFInfo
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- KR100926798B1 KR100926798B1 KR1020080029821A KR20080029821A KR100926798B1 KR 100926798 B1 KR100926798 B1 KR 100926798B1 KR 1020080029821 A KR1020080029821 A KR 1020080029821A KR 20080029821 A KR20080029821 A KR 20080029821A KR 100926798 B1 KR100926798 B1 KR 100926798B1
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- South Korea
- Prior art keywords
- mushroom
- inonotus
- antioxidant
- phellinus
- formula
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Abstract
본 발명은 페리너스 속 버섯 또는 이노노투스 속 버섯의 균사체 배양물로부터 분리된 히스피딘 유사체를 포함하는 항산화 조성물에 관한 것으로서, 더욱 상세하게는 페리너스 속(Phellinus sp.) 버섯 또는 이노노투스 속(Inonotus sp.) 버섯의 균사체 배양물로부터 분리된 항산화 화합물들, 즉 3,14-비히스피디닐(3,14-bihispidinyl), 하이폴로민 B(hypholomine B), 1,1-디스티릴피릴에탄(1,1-distyrylpyrylethan)이 수퍼옥사이드 라티칼 소거 효과, ABTS 라디칼 소거 효과 및 DPPH 라디칼 소거 효과를 나타내어 항산화 활성이 있음을 밝히고, 이들 화합물이 유효성분으로 함유되어 암을 비롯하여 동맥경화, 관절염, 뇌졸중, 파킨슨병, 알츠하이머병, 자가면역질환 등의 각종 질병에 대한 예방 및 치료와 피부 노화 억제를 위한 의약품, 화장품 소재, 기능성 식품, 또는 식품첨가물로서 유용한 항산화 조성물에 관한 것이다.The present invention relates to an antioxidant composition comprising a hispidine analogue isolated from a mycelium culture of the genus Perinus or Inotus mushroom, and more specifically, the genus Phellinus sp . ( Inonotus sp . ) Antioxidant compounds isolated from mycelial cultures of mushrooms, namely 3,14-bihispidinyl, hypholomine B, 1,1-distyrylpyryl Ethane (1,1-distyrylpyrylethan) exhibits superoxide radical scavenging effect, ABTS radical scavenging effect, and DPPH radical scavenging effect, showing antioxidant activity, and these compounds are included as active ingredients, including cancer, arteriosclerosis, arthritis, As a medicine, cosmetic material, functional food, or food additive for the prevention and treatment of various diseases such as stroke, Parkinson's disease, Alzheimer's disease, autoimmune disease, etc. It relates to useful antioxidant compositions.
페리너스 속(Phellinus sp.) 버섯, 이노노투스 속(Inonotus sp.) 버섯, 하이폴로민 B, 1,1-디스티릴피릴에탄, 3,14-비히스피디닐 Perinus sp. Mushroom, Inonotus sp. Mushroom, Hypolomin B, 1,1-Distyrylpyrylethane, 3,14-bihispidinyl
Description
본 발명은 페리너스 속 버섯 또는 이노노투스 속 버섯의 균사체 배양물로부터 분리된 히스피딘 유사체를 포함하는 항산화 조성물에 관한 것으로서, 더욱 상세하게는 페리너스 속(Phellinus sp.) 버섯 또는 이노노투스 속(Inonotus sp.) 버섯의 균사체 배양물로부터 분리된 항산화 화합물들, 즉 3,14-비히스피디닐(3,14-bihispidinyl), 하이폴로민 B(hypholomine B), 1,1-디스티릴피릴에탄(1,1-distyrylpyrylethan)이 수퍼옥사이드 라티칼 소거 효과, ABTS 라디칼 소거 효과 및 DPPH 라디칼 소거 효과를 나타내어 항산화 활성이 있음을 밝히고, 이들 화합물이 유효성분으로 함유되어 암을 비롯하여 동맥경화, 관절염, 뇌졸중, 파킨슨병, 알츠하이머병, 자가면역질환 등의 각종 질병에 대한 예방 및 치료와 피부 노화 억제를 위한 의약품, 화장품 소재, 기능성 식품, 또는 식품첨가물로서 유용한 항산화 조성물에 관한 것이다.The present invention relates to an antioxidant composition comprising a hispidine analogue isolated from a mycelium culture of the genus Perinus or Inotus mushroom, and more specifically, the genus Phellinus sp . ( Inonotus sp . ) Antioxidant compounds isolated from mycelial cultures of mushrooms, namely 3,14-bihispidinyl, hypholomine B, 1,1-distyrylpyryl Ethane (1,1-distyrylpyrylethan) exhibits superoxide radical scavenging effect, ABTS radical scavenging effect, and DPPH radical scavenging effect, showing antioxidant activity, and these compounds are included as active ingredients, including cancer, arteriosclerosis, arthritis, As a medicine, cosmetic material, functional food, or food additive for the prevention and treatment of various diseases such as stroke, Parkinson's disease, Alzheimer's disease, autoimmune disease, etc. It relates to useful antioxidant compositions.
인간의 몸은 산소를 최종 전자수용체로 하는 호흡을 통해 에너지를 획득한다. 그러나 이와 같이 생명유지에 절대적으로 필요한 산소이지만 안정한 분자상태인 기저 삼중항산소가 각종 물리적, 화학적, 환경적 요인 등에 의하여 수퍼옥사이드 라디칼(O2 -), 하이드록실 라디칼(HOㆍ), 과산화수소(H2O2), 일중항산소(1O2)와 같은 반응성이 매우 큰 자유 라디칼 또는 활성산소(reactive oxygen species)로 전환되면 생체에 치명적인 산소독성을 일으키는 양면성을 지니고 있다. 즉, 이들 활성산소는 세포 구성성분들인 지질, 단백질, 당, DNA 등에 대하여 비선택적, 비가역적인 파괴작용을 함으로써 암을 비롯하여 동맥경화, 관절염, 뇌졸중, 파킨슨병, 알츠하이머병, 자가면역질환 등의 각종 질병 원인으로 작용함은 물론이고 노화 원인으로 작용하는 것으로 알려져 있다. 따라서, 활성산소를 제거시키거나 유리 라디칼 생성을 억제시키는 항산화 물질들은 과량 생성된 활성산소에 의해 발생한 암을 비롯하여 동맥경화, 관절염, 뇌졸중, 파킨슨병, 알츠하이머병, 자가면역질환 등의 각 질병의 예방 및 치료와 피부 노화억제를 목적으로 이용될 수 있다[Hajieva, P.; Behl, C. Antioxidant as a potential therapy against age-related neurodegenerative diseases: amyloid Beta toxicity and Alzheimer's disease. Curr. Pharm. Des. 12(6): 699-704. 2006. Cherubini, A.; Vigna, G. B.; Zuliani, G.; Ruggiero, C.; Senin, U.; Fellin, R. Role of antioxidants in atherosclerosis. Curr. Pharm. Des. 11((16): 2017-2032. 2005. Zhao, B. Natural antioxidants for neurodegenerative diseases. Mol. Neurobiol. 31: 283-293, 2005. Murakami, A.; Ohigashi, H. Cancer-preventive antioxidants that attenuate free radical generation by inflammatory cells. Biol. Chem. 387: 387-392. 2006]. The human body acquires energy through breathing, which uses oxygen as the final electron acceptor. However, oxygen, which is absolutely necessary for life support, is a basic triplet oxygen in stable molecular state due to various physical, chemical and environmental factors such as superoxide radical (O 2 − ), hydroxyl radical (HO ·), and hydrogen peroxide (H). 2 O 2 ), when converted to highly reactive free radicals or reactive oxygen species such as singlet oxygen ( 1 O 2 ) has a double-sided to cause fatal oxygen toxicity to the living body. That is, these free radicals are non-selective and irreversible destructive action on cell components lipids, proteins, sugars, DNA, etc., such as cancer, arteriosclerosis, arthritis, stroke, Parkinson's disease, Alzheimer's disease, autoimmune diseases It is known to act as a cause of disease as well as to cause aging. Therefore, antioxidants that remove free radicals or inhibit free radical production include cancers caused by excessively produced free radicals, as well as prevention of diseases such as arteriosclerosis, arthritis, stroke, Parkinson's disease, Alzheimer's disease, and autoimmune diseases. And for the purpose of treatment and skin aging [Hajieva, P .; Behl, C. Antioxidant as a potential therapy against age-related neurodegenerative diseases: amyloid Beta toxicity and Alzheimer's disease. Curr. Pharm. Des. 12 (6): 699-704. 2006. Cherubini, A .; Vigna, GB; Zuliani, G .; Ruggiero, C .; Senin, U .; Fellin, R. Role of antioxidants in atherosclerosis. Curr. Pharm. Des. 11 ((16): 2017-2032. 2005. Zhao, B. Natural antioxidants for neurodegenerative diseases.Mol. Neurobiol. 31: 283-293, 2005. Murakami, A .; Ohigashi, H. Cancer-preventive antioxidants that attenuate free radical generation by inflammatory cells.Biol. Chem. 387: 387-392. 2006].
지금까지 알려진 합성 항산화제로는 BHA(Butylated hydroxy anisole), BHT(Butylated hydroxy toluene) 및 NDGA(Nordihydro-guaiaretic acid) 등이 있으며, 천연 항산화제로는 수퍼옥시다이드 디뮤스타제, 퍼옥시다아제, 카탈라아제, 글루타치온 퍼옥시다아제 등의 항산화 효소와 비타민 E, 비타민 C, 글루타치온 등의 비효소적 항산화 물질이 있다. 그러나, 합성 항산화제는 생체 내에서 독성을 나타내어 알러지와 종양을 발생시킬 수 있으며, 온도에 약해 한번 열을 가하면 쉽게 파괴되는 단점이 있다. 반면에 천연 항산화제는 합성 항산화제에 비교하여 생체에 안전한 장점은 있지만, 그 효과가 약하다는 단점이 있다. 따라서, 항산화 활성이 탁월하고 보다 생체에 안전한 새로운 천연 항산화제의 개발이 절실히 요구되고 있다. 실제로 자유 라디칼을 소거할 수 있는 천연 항산화제 개발을 통하여 암을 비롯하여 동맥경화, 관절염, 뇌졸중, 파킨슨병, 알츠하이머병, 자가면역질환 등의 각 질병에 대한 치료제 및 노화 억제제로 이용하고자 하는 노력은 계속적으로 있어 왔다.Synthetic antioxidants known to date include butylated hydroxy anisole (BHA), butylated hydroxy toluene (BHT), and nordihydro-guaiaretic acid (NDGA) .Natural antioxidants include superoxidide dimustase, peroxidase, catalase, and glutathione. Antioxidant enzymes such as peroxidase and non-enzymatic antioxidants such as vitamin E, vitamin C and glutathione. However, synthetic antioxidants are toxic in vivo and can cause allergies and tumors. On the other hand, natural antioxidants have the advantages of being safe to the living body compared to synthetic antioxidants, but have the disadvantage of their weakness. Therefore, there is an urgent need for the development of new natural antioxidants that are excellent in antioxidant activity and safer in vivo. Indeed, the development of natural antioxidants capable of scavenging free radicals has led to continued efforts to use them as therapeutic agents and aging inhibitors for cancer, arteriosclerosis, arthritis, stroke, Parkinson's disease, Alzheimer's disease and autoimmune diseases. I have been.
최근 웰빙 열풍과 함께 건강식품으로 각광받고 있는 버섯은 식용뿐만 아니라 의약품으로 이용되고 있다. 버섯은 고등균류(Higher fungi) 중 담자균아 강(Basidiomycotina)과 자낭균아강(Ascomycotina) 및 불완전균류(Imperfect fungi)에서 균사체가 영양대사를 한 결과 대사산물이 축적된 자실체의 형태로 나타나는 것으로 지구상에는 20,000 여종이 존재하는 것으로 알려져 있고 우리나라에는 68과 261속 992종이 보고 되어 있으며, 이 중 328종이 식용 및 약용버섯으로 알려져 있다. 버섯의 약리효과는 항암, 혈중 콜레스테롤 저하, 혈압 강하, 항바이러스, 면역 증강, 항균, 인터페론 유도 효과 등이 알려져 있으며, 지금까지 알려진 약용 버섯들은 다당체에 의한 항암활성이 주류를 이룬다. 상기와 같은 버섯의 약리효과는 버섯의 항산화 활성에 의해 유추될 수 있는 것으로 판단된다.Recently, mushrooms, which have been spotlighted as health foods along with the well-being fever, are being used as medicines as well as food. Mushrooms appear in the form of fruiting bodies where metabolites accumulate as a result of nutritional metabolism in Bacillidiomycotina, Ascomycotina and Imperfect fungi among higher fungi. It is known that there are about 20,000 species and 992 species of 68 and 261 genera are reported in Korea, and 328 of them are known as edible and medicinal mushrooms. The pharmacological effects of the mushrooms are known to be anti-cancer, lowering blood cholesterol, lowering blood pressure, antiviral, immune boosting, antibacterial, interferon-inducing effect, so far known medicinal mushrooms are the main anticancer activity of the polysaccharide. It is believed that the pharmacological effect of the mushroom can be inferred by the antioxidant activity of the mushroom.
특히, 가장 많이 사용되고 있는 약용 버섯인 상황버섯(Phellinus linteus)과, 차가 버섯(Inonotus obliquus)은 그 약효로 인해 의약품 및 건강 식품으로 잘 알려져 있다. 페리너스 속과 이노노투스 속에 속하는 이들 버섯들은 공통적으로 노란색의 색소를 생산하며, 이들 색소는 버섯의 다양한 생리활성과 관련되어 있을 것으로 추정되고 있다. 본 연구는 상기와 같은 노란색 색소로부터 신규한 항산화 화합물 펠리닌 A, B 및 C를 분리하였다. 또한, 본 발명에서 밝힌 화합물들에 대한 항산화 활성은 어느 문헌에서도 밝혀진 바 없다.In particular, the most used medicinal mushrooms ( Phellinus linteus ) and chaga ( Inonotus obliquu s) are well known as medicines and health foods due to their efficacy. These mushrooms, belonging to the genus Perinus and Innotus, commonly produce yellow pigments, which are believed to be related to the various physiological activities of the mushrooms. The present study isolated the novel antioxidant compounds pelinin A, B and C from the yellow pigment. In addition, the antioxidant activity of the compounds identified in the present invention has not been found in any literature.
이에, 본 발명자들은 페리너스(Phellinus) 속 버섯 예를 들면, 상황버섯(Phellinus linteus), 찔레버섯(Phellinus ribis) 및 이노노투스(Inonotus) 속 버섯 예를 들면, 차가버섯(Inonotus obliquus), 기와층버섯(Inonotus xeranticus)에 속하는 버섯균주의 배양액으로부터 항산화 활성을 나타내는 화합물을 탐색하여 항산화 활성 물질을 분리, 정제하여 구조를 결정한 결과, 활성 물질은 펠리닌 A(phellinin A), 펠리닌 B(phellinin B, 펠리닌 B1↔펠리닌 B2)와 펠리닌 C(phellinin C)로 명명된 신규 화합물들과 이미 알려진 바 있는 3,14-비히스피디닐(3,14-bihispidinyl), 하이폴로민 B(hypholomine B), 1,1-디스티릴피릴에탄(1,1-distyrylpyrylethan)을 동정하고 규명하였고, 각 버섯 균주에서 공통적으로 상기 화합물들이 생산되었고, 이들에 대한 항산화 활성을 확인하여 동맥경화, 암, 관절염, 뇌졸중, 파킨슨병, 알츠하이머병, 자가면역질환 등의 각 질병의 예방 및 치료와 피부 노화 억제를 목적으로 이용할 수 있음을 밝힘으로써 본 발명을 완성하게 되었다.Accordingly, the inventors of the present invention, the mushrooms of the genus Phellinus , for example, Phellinus linteus , Phellinus ribis and mushrooms of the genus Inonotus , for example, chaga ( Inonotus obliquus ), roof tiles From the cultures of mushroom strains belonging to Inonotus xeranticus , the compounds showing antioxidant activity were searched to determine their structure by separating and purifying the antioxidant active substances. As a result, the active substances were called phellinin A and phellinin B. B, novel compounds named fellin B1 ↔ pellinine B2) and phellinin C, as well as 3,14-bihispidinyl, and hypolomin B (also known as hypholomine B) and 1,1-distyrylpyrylethanol were identified and identified, and these compounds were produced in common in each mushroom strain, and their antioxidant activity was confirmed by confirming their antioxidant activity against atherosclerosis, cancer, Arthritis, Stroke, Parkinson , Alzheimer's disease, by identifying that can be used for the purpose of preventing and treating skin aging and inhibition of each disease, such as autoimmune diseases, thereby completing the present invention.
따라서, 본 발명은 3,14-비히스피디닐(3,14-bihispidinyl), 하이폴로민 B(hypholomine B) 및 1,1-디스티릴피릴에탄(1,1-distyrylpyrylethan) 중에서 선택된 1종 이상의 히스피딘 유사체를 유효성분으로 함유하는 항산화 조성물을 제공하는데 그 목적이 있다.Accordingly, the present invention provides at least one selected from 3,14-bihispidinyl, hypopolmine B, and 1,1-distyrylpyrylethan. It is an object to provide an antioxidant composition containing a hispidine analog as an active ingredient.
본 발명은 다음 화학식 4, 5 및 6으로 표시되는 히스피딘 유사체 중에서 선택된 1종 또는 2종 이상을 유효성분으로 함유하는 항산화 조성물을 또 다른 특징으로 한다.The present invention is another feature of the antioxidant composition containing one or two or more selected from the hispidine analogs represented by the following formulas (4), (5) and (6) as an active ingredient.
이와 같은 본 발명을 더욱 상세히 설명하면 다음과 같다.Referring to the present invention in more detail as follows.
본 발명은 페리너스 속(Phellinus sp.) 버섯 또는 이노노투스 속(Inonotus sp.) 버섯의 균사체 배양물로부터 분리된 항산화 화합물들, 즉 3,14-비히스피디닐(3,14-bihispidinyl), 하이폴로민 B(hypholomine B), 1,1-디스티릴피릴에탄(1,1-distyrylpyrylethan), 펠리닌 A(phellinin A), 펠리닌 B(phellinin B, 펠리닌 B1↔펠리닌 B2) 및 펠리닌 C(phellinin C)가 수퍼옥사이드 라티칼 소거 효과, ABTS 라디칼 소거 효과 및 DPPH 라디칼 소거 효과를 나타내어 항산화 활성이 있음을 밝히고 있어, 암을 비롯하여 동맥경화, 관절염, 뇌졸중, 파킨슨병, 알츠하이머병, 자가면역질환 등의 각종 질병에 대한 예방 및 치료와 피부 노화 억제를 위한 의약품, 화장품 소재, 기능성 식품, 또는 식품첨가물로서 유용한 페리너스 속 버섯 또는 이노노투스 속 버섯 균사체 배양물로부터 분리된 항산화 화합물에 관한 것이다.The present invention relates to antioxidant compounds isolated from mycelial culture of Phellinus sp . Or Inonotus sp . Mushrooms, namely 3,14-bihispidinyl. Hypolomine B, 1,1-distyrylpyrylethan, phellinin A, phellinin B, pelinin B1 ↔ pelinin B2, and Phellinin C has superoxide radical scavenging effect, ABTS radical scavenging effect, and DPPH radical scavenging effect, indicating that it has antioxidant activity, including cancer, arteriosclerosis, arthritis, stroke, Parkinson's disease, Alzheimer's disease, Antioxidant compounds isolated from mushroom mycelium cultures of Perinus or Inototus mushrooms useful as medicines, cosmetic materials, functional foods or food additives for the prevention and treatment of various diseases such as autoimmune diseases and skin aging. About The.
본 발명이 특징으로 하는 페리너스 속 및 이노노투스 속 버섯을 알콜류를 이용하여 표면 소독한 후, 무균상자에서 멸균된 칼을 이용하여 소독된 버섯 조직의 절편을 분리하여 포테이토-덱스트로즈 아가 배지에 올려놓은 후 일정 기간동안 배양하여 균사를 확보한다. 또한, 버섯 포자로부터 직접 발아를 통하여 균사를 확보할 수 있다. 이 같은 방법의 유효성을 입증하기 위하여 본 발명에서는 페리너스 속 버섯을 대표하여 상황버섯(Phellinus linteus KCTC 10975BP)과, 이노노투스 속 버섯을 대표하여 기와층버섯(Inonotus xeranticus KCTC 10976BP)을 실험에 사용하였으며, 이 외에도 페리너스 속 균주로서 페리너스 리비스(Phellinus ribis), 페리너스 이그니아리우스(Phellinus igniarius) 페리너스 바우미(Phellinus baumii), 페리너스 로부스투스(Phellinus robustus), 페리너스 포필리우스(Phellinus popilius)와 이노노투스 속 균주로서 이노노투스 오블리쿼스(Inonotus obliquus) 등은 상기 상황버섯과 기와층버섯의 분리과정과 동일하게 수행하면 동일한 화합물을 얻을 수 있음을 확인할 수 있다.After sterilizing the mushrooms of the genus Perinus and Inototus using an alcohol, the sections of the sterilized mushroom tissue are separated using a sterilized knife in a sterile box. After placing it on, incubate for a certain period to secure mycelia. In addition, it is possible to secure mycelia through germination directly from mushroom spores. In order to prove the effectiveness of the method, the present invention uses a situation mushroom ( Phellinus linteus KCTC 10975BP) on behalf of the genus Perinus and a tile layer mushroom ( Inonotus xeranticus KCTC 10976BP) on behalf of the genus Inonotus for the experiment. In addition, the strains of the genus Perinus are Phellinus ribis and Perinus igliarius igniarius ) Phellinus baumii , Phellinus robustus , Phellinus popilius and Inonotus strains, Inonotus obliquus obliquus ) and the like can be seen that the same compound can be obtained by performing the same process as the separation of the situation mushroom and tile layer mushroom.
균사체 배양물로부터 활성물질을 분리하기 위해서는 균사체 배양물을 클로로포름류, 에틸아세테이트류 등의 유기 용매에 의하여 추출, 물의 분배, 컬럼크로마토그래피 등 유용성분의 분리 및 추출에 이용되는 공지의 방법을 단독 또는 적합하게 조합하여 용이하게 얻을 수 있다. 조추출물은 필요에 따라서 상법에 따라서 더욱 정제할 수 있다. In order to separate the active substance from the mycelium culture, the mycelium culture is extracted by an organic solvent such as chloroform and ethyl acetate, water distribution, separation of useful components such as column chromatography, and extraction alone or by a known method. It can obtain easily combining suitably. The crude extract can be further purified according to a commercial method as needed.
본 발명에서는 페리너스(Phellinus) 속 버섯 또는 이노노투스(Inonotus) 속 버섯 균주의 배양물을 사용한다. 본 발명에 따른 이들 균주의 배양물과 이 배양물로부터 활성물질로서 히스피딘 유도체를 효율적으로 분리할 수 있는 바람직한 방법은 다음과 같다: In the present invention, a culture of mushrooms of the genus Perhellus ( Phellinus ) or Inonotus ( Inonotus ) is used. Cultures of these strains according to the present invention and the preferred method for efficiently separating hispidine derivatives as active substances from the cultures are as follows:
본 발명은The present invention
1) 페리너스 속(Phellinus sp.) 버섯 또는 이노노투스 속(Inonotus sp.) 버섯 자실체를 표면 소독 후, 멸균한 상태에서 균주를 확보한 다음, 포테이토-덱스트로즈 함유 배지를 이용하여 25 ~ 30 ℃에서 7 ~ 20일간 진탕 배양하여 배양물을 얻는 단계;1) After surface disinfection of Phellinus sp. Mushroom or Inonotus sp. Mushroom fruiting body, the strains were secured in sterilized state, and then 25 ~ 25 using potato-dextrose-containing medium. Shaking culture at 30 ° C. for 7-20 days to obtain a culture;
2) 상기 배양물을 탄소수 1 내지 6의 지방족 알콜 또는 탄소수 5 내지 10의 지방족 탄화수소의 용매로 추출하여 용매 추출물을 얻는 단계; 및2) extracting the culture with a solvent of aliphatic alcohol having 1 to 6 carbon atoms or aliphatic hydrocarbon having 5 to 10 carbon atoms to obtain a solvent extract; And
3) 상기 용매 추출물에 메탄올로 세파덱스 LH-20 컬럼 크로마토그래피를 수행하고 다시 60~80% 메탄올 수용액으로 세파덱스 LH-20 컬럼 크로마토그래피를 실시하여 활성 분획물을 얻은 후, 활성 분획물에 대하여 40~60% 메탄올 수용액을 사용하여 RP-TLC를 수행하여 3,14-비히스피디닐(3,14-bihispidinyl)를 분리한다. 3) Sepadex LH-20 column chromatography with methanol was performed on the solvent extract, and then Sepadex LH-20 column chromatography was performed with 60-80% aqueous methanol solution to obtain an active fraction. RP-TLC was performed using 60% aqueous methanol solution to separate 3,14-bihispidinyl.
또한, 본 발명은In addition, the present invention
1) 페리너스 속(Phellinus sp.) 버섯 또는 이노노투스 속(Inonotus sp.) 버섯 자실체를 표면 소독 후, 멸균한 상태에서 균주를 확보한 다음, 포테이토-덱스트로즈 함유 배지를 이용하여 25 ~ 30 ℃에서 7 ~ 20일간 진탕 배양하여 배양물을 얻는 단계;1) After surface disinfection of Phellinus sp. Mushroom or Inonotus sp. Mushroom fruiting body, the strain was secured in sterilized state, and then 25 ~ 25 Shaking culture at 30 ° C. for 7-20 days to obtain a culture;
2) 상기 배양물을 탄소수 1 내지 6의 지방족 알콜 또는 탄소수 5 내지 10의 지방족 탄화수소의 용매로 추출하여 용매 추출물을 얻는 단계; 및2) extracting the culture with a solvent of aliphatic alcohol having 1 to 6 carbon atoms or aliphatic hydrocarbon having 5 to 10 carbon atoms to obtain a solvent extract; And
3) 상기 용매 추출물에 메탄올로 세파덱스 LH-20 컬럼 크로마토그래피를 수행하고 다시 60~80% 메탄올 수용액으로 세파덱스 LH-20 컬럼 크로마토그래피를 실시하여 활성 분획물을 얻은 후, 활성 분획물에 대하여 60~80% 메탄올 수용액을 사용하여 RP-TLC를 실시하여 하이폴로민 B(hypholomine B)를 분리한다. 또는, 상기 활성 분획물에 고속 액체 크로마토그래피(preparative HPLC)를 40~60% 메탄올(0.04% TFA)을 전개용매로 하여 하이폴로민 B(hypholomine B)를 분리할 수 있다.3) Sepadex LH-20 column chromatography with methanol was performed on the solvent extract, and Sepadex LH-20 column chromatography was performed with 60-80% aqueous methanol solution to obtain an active fraction. RP-TLC was performed using 80% aqueous methanol solution to separate hypolomine B. Alternatively, hypochloromine B may be separated by high-performance liquid chromatography (preparative HPLC) using 40-60% methanol (0.04% TFA) as a developing solvent.
본 발명은The present invention
1) 페리너스 속(Phellinus sp.) 버섯 또는 이노노투스 속(Inonotus sp.) 버섯 자실체를 표면 소독 후, 멸균한 상태에서 균주를 확보한 다음, 포테이토-덱스트로즈 함유 배지를 이용하여 25 ~ 30 ℃에서 7 ~ 20일간 진탕 배양하여 배양물을 얻는 단계;1) After surface disinfection of Phellinus sp. Mushroom or Inonotus sp. Mushroom fruiting body, the strain was secured in sterilized state, and then 25 ~ 25 Shaking culture at 30 ° C. for 7-20 days to obtain a culture;
2) 상기 배양물을 탄소수 1 내지 6의 지방족 알콜 또는 탄소수 5 내지 10의 지방족 탄화수소의 용매로 추출하여 용매 추출물을 얻는 단계; 및2) extracting the culture with a solvent of aliphatic alcohol having 1 to 6 carbon atoms or aliphatic hydrocarbon having 5 to 10 carbon atoms to obtain a solvent extract; And
3) 상기 용매 추출물에 메탄올로 세파덱스 LH-20 컬럼 크로마토그래피를 수행하고 다시 60~80% 메탄올 수용액으로 세파덱스 LH-20 컬럼 크로마토그래피를 실시하여 활성 분획물을 얻은 후, 활성 분획물에 85~95% 메탄올 수용액을 전개용매로 RP-TLC를 실시하여 1,1-디스티릴피릴에탄(1,1-distyrylpyrylethan)을 분리한다. 또한, 상기 활성 분획물에 40~60% 메탄올(0.04% TFA)을 전개용매로 고속 액체 크 로마토그래피(preparative HPLC)를 수행하여 1,1-디스티릴피릴에탄을 분리할 수 있다.3) Sepadex LH-20 column chromatography with methanol was performed on the solvent extract, and Sepadex LH-20 column chromatography was again performed with 60-80% aqueous methanol solution to obtain an active fraction, and then 85-95 to the active fraction. 1,1-distyrylpyrylethanol was separated by performing RP-TLC with a% methanol aqueous solution as a developing solvent. In addition, the active fraction may be subjected to high performance liquid chromatography (preparative HPLC) with 40 to 60% methanol (0.04% TFA) as a developing solvent to separate 1,1-distyrylpyrylethane.
본 발명은The present invention
1) 페리너스 속(Phellinus sp.) 버섯 또는 이노노투스 속(Inonotus sp.) 버섯 자실체를 표면 소독 후, 멸균한 상태에서 균주를 확보한 다음, 포테이토-덱스트로즈 함유 배지를 이용하여 25 ~ 30 ℃에서 7 ~ 20일간 진탕 배양하여 배양물을 얻는 단계;1) After surface disinfection of Phellinus sp. Mushroom or Inonotus sp. Mushroom fruiting body, the strains were secured in sterilized state, and then 25 ~ 25 using potato-dextrose-containing medium. Shaking culture at 30 ° C. for 7-20 days to obtain a culture;
2) 상기 배양물을 탄소수 1 내지 6의 지방족 알콜 또는 탄소수 5 내지 10의 지방족 탄화수소의 용매로 추출하여 용매 추출물을 얻는 단계; 및2) extracting the culture with a solvent of aliphatic alcohol having 1 to 6 carbon atoms or aliphatic hydrocarbon having 5 to 10 carbon atoms to obtain a solvent extract; And
3) 상기 용매 추출물에 메탄올로 세파덱스 LH-20 컬럼 크로마토그래피를 수행하고 다시 60~80% 메탄올 수용액으로 세파덱스 LH-20 컬럼 크로마토그래피를 실시하여 활성 분획물을 얻은 후, 활성 분획물에 40 ~ 90%의 메탄올 수용액을 용매로 C-18 세팍 카트리지(sepak catridge)로 분획하여 85~95% 메탄올 수용액으로 용출된 분획에서 펠리닌 A(phellinin A)를 분리한다.3) Sepadex LH-20 column chromatography with methanol was performed on the solvent extract, and Sepadex LH-20 column chromatography was again performed with 60-80% aqueous methanol solution to obtain an active fraction. The aqueous methanol solution of% was fractionated with a C-18 Sepak cartridge (solpak catridge) as a solvent to separate the phellinin A from the fraction eluted with 85 ~ 95% methanol solution.
본 발명은The present invention
1) 페리너스 속(Phellinus sp.) 버섯 또는 이노노투스 속(Inonotus sp.) 버섯 자실체를 표면 소독 후, 멸균한 상태에서 균주를 확보한 다음, 포테이토-덱스트로즈 함유 배지를 이용하여 25 ~ 30 ℃에서 7 ~ 20일간 진탕 배양하여 배양물을 얻는 단계;1) After surface disinfection of Phellinus sp. Mushroom or Inonotus sp. Mushroom fruiting body, the strain was secured in sterilized state, and then 25 ~ 25 Shaking culture at 30 ° C. for 7-20 days to obtain a culture;
2) 상기 배양물을 탄소수 1 내지 6의 지방족 알콜 또는 탄소수 5 내지 10의 지방족 탄화수소의 용매로 추출하여 용매 추출물을 얻는 단계; 및2) extracting the culture with a solvent of aliphatic alcohol having 1 to 6 carbon atoms or aliphatic hydrocarbon having 5 to 10 carbon atoms to obtain a solvent extract; And
3) 상기 용매 추출물에 메탄올로 세파덱스 LH-20 컬럼 크로마토그래피를 수행하고 다시 60~80% 메탄올 수용액으로 세파덱스 LH-20 컬럼 크로마토그래피를 실시하여 활성 분획물을 얻은 후, 활성 분획물에 40 ~ 90%의 메탄올 수용액으로 C-18 세팍 카트리지(sepak catridge)를 사용하여 분획한 다음, 60 ~ 70%의 메탄올 수용액 분획물을 60~80% 메탄올 수용액으로 세파덱스 LH-20 컬럼 크로마토그래피를 실시하여 펠리닌 B(phellinin B, 펠리닌 B1↔펠리닌 B2)를 분리한다. 3) Sepadex LH-20 column chromatography with methanol was performed on the solvent extract, and Sepadex LH-20 column chromatography was again performed with 60-80% aqueous methanol solution to obtain an active fraction. Fractionated using a C-18 Sepak cartridge with aqueous methanol solution of%, and then fractionated 60-70% aqueous methanol solution with Sephadex LH-20 column chromatography with 60-80% aqueous methanol solution. Separate B (phellinin B, pelinin B1 ↔ pelinin B2).
본 발명은The present invention
1) 페리너스 속(Phellinus sp.) 버섯 또는 이노노투스 속(Inonotus sp.) 버섯 자실체를 표면 소독 후, 멸균한 상태에서 균주를 확보한 다음, 포테이토-덱스트로즈 함유 배지를 이용하여 25 ~ 30 ℃에서 7 ~ 20일간 진탕 배양하여 배양물을 얻는 단계;1) After surface disinfection of Phellinus sp. Mushroom or Inonotus sp. Mushroom fruiting body, the strain was secured in sterilized state, and then 25 ~ 25 Shaking culture at 30 ° C. for 7-20 days to obtain a culture;
2) 상기 배양물을 탄소수 1 내지 6의 지방족 알콜 또는 탄소수 5 내지 10의 지방족 탄화수소의 용매로 추출하여 용매 추출물을 얻는 단계; 및2) extracting the culture with a solvent of aliphatic alcohol having 1 to 6 carbon atoms or aliphatic hydrocarbon having 5 to 10 carbon atoms to obtain a solvent extract; And
3) 상기 용매 추출물에 메탄올로 세파덱스 LH-20 컬럼 크로마토그래피를 수행하고 다시 60~80% 메탄올 수용액으로 세파덱스 LH-20 컬럼 크로마토그래피를 실시하여 활성 분획물을 얻은 후, 활성 분획물에 40 ~ 90%의 메탄올 수용액으로 C-18 세팍 카트리지(sepak catridge)를 사용하여 분획한 다음, 60 ~ 70%의 메탄올 수용액 분획물을 60~80% 메탄올 수용액으로 세파덱스 LH-20 컬럼 크로마토그래피를 실시하여 펠리닌 C(Phellinin C)를 분리한다. 3) Sepadex LH-20 column chromatography with methanol was performed on the solvent extract, and Sepadex LH-20 column chromatography was again performed with 60-80% aqueous methanol solution to obtain an active fraction. Fractionated using a C-18 Sepak cartridge with aqueous methanol solution of%, and then fractionated 60-70% aqueous methanol solution with Sephadex LH-20 column chromatography with 60-80% aqueous methanol solution. Separate C (Phellinin C).
상기 분리방법에 각각의 2) 단계에서 사용되는 용매로는 바람직하게 메탄올, 에탄올, 아세톤, 프로판올, 에틸아세테이트 등이 적합하다.The solvent used in each step 2) in the separation method is preferably methanol, ethanol, acetone, propanol, ethyl acetate and the like.
또한, 본 발명의 화합물은 버섯 성분의 분리 추출에 이용되는 공지의 방법을 단독 또는 적합하게 조합하여 얻을 수 있다. In addition, the compound of the present invention can be obtained by combining a known method used for separate extraction of mushroom components alone or in a suitable combination.
이렇게 얻어진 화합물들의 물리화학적 특성은 다음과 같다. The physical and chemical properties of the compounds thus obtained are as follows.
모든 화합물은 노란색의 분말로 획득되었다.All compounds were obtained as a yellow powder.
상기 화합물의 분자식을 결정하기 위하여 ESI-mass를 측정한 결과, 3,14-비히스피디닐은 분자식 C26H18O10, 분자량 490이었으며, 하이폴로민 B는 분자식 C26H18O10, 분자량 490, 1,1-디스티릴피릴에탄은 분자식 C28H22O10 , 분자량 518, 펠리닌 A는 분자식 C33H20O13, 분자량 448, 펠리닌 B는 분자식 C18H18O6, 분자량 330, 펠리닌 C는 분자식 C19H20O6, 분자량 344로 각각 결정되었다.As a result of measuring the ESI-mass to determine the molecular formula of the compound, 3,14-bihispidinyl was the molecular formula C 26 H 18 O 10 , molecular weight 490, the hypolomine B is the molecular formula C 26 H 18 O 10 ,
UV 스펙트럼을 측정한 결과 이들 화합물 모두 250 nm 부근 및 370 ~ 390 nm에서 최대 흡수피크를 나타내었다.The UV spectra measured the maximum absorption peaks at all of these compounds at around 250 nm and at 370-390 nm.
NMR 결과와 상기의 물리화학적 특성을 근거로 분리된 화합물들의 화학구조를 해석하였다.Based on the NMR results and the physicochemical properties, the chemical structures of the isolated compounds were analyzed.
본 발명에 따른 화합물들은 1) 크산틴/크산틴 옥시다아제 효소계를 이용한 수퍼옥사이드 라디칼, 2) ABTS 라디칼, 3) DPPH 라디칼을 이용하여 항산화 물질로 알려져 있는 카페인산(caffeic acid), BHA, 트롤록스(trolox)와 비교하여 항산화 활성을 나타내었다. Compounds according to the invention are 1) superoxide radicals using xanthine / xanthine oxidase enzyme system, 2) ABTS radicals, 3) caffeic acid, BHA, trolox ( compared with trolox).
이러한 항산화 활성으로부터 암을 비롯하여 동맥경화, 관절염, 뇌졸중, 파킨슨병, 알츠하이머병, 자가면역질환 등의 각종 질병에 대한 예방 및 치료와 피부 노화 억제를 위한 의약품, 화장품 소재 또는 식품으로 적용가능하다.From these antioxidant activities, it is applicable to medicines, cosmetic materials or foods for the prevention and treatment of various diseases such as cancer, arteriosclerosis, arthritis, stroke, Parkinson's disease, Alzheimer's disease, autoimmune diseases and skin aging.
따라서, 본 발명에서는 페리너스 속(Phellinus sp.) 버섯 또는 이노노투스 속(Inonotus sp.) 버섯의 균사체 배양물로부터 얻은 3,14-비히스피디닐(3,14-bihispidinyl), 하이폴로민 B(hypholomine B), 1,1-디스티릴피릴에탄(1,1-distyrylpyrylethan), 펠리닌 A(phellinin A), 펠리닌 B(phellinin B, 펠리닌 B1↔펠리닌 B2) 및 펠리닌 C(phellinin C) 중에서 선택된 1종 또는 2종 이상을 유효성분으로 함유하는 항산화 조성물을 포함한다.Therefore, in the present invention, 3,14-bihispidinyl, hypolomin obtained from the mycelium culture of Phellinus sp . Or Inonotus sp . Hypholomine B, 1,1-distyrylpyrylethan, phellinin A, phellinin B, pelinin B1↔pellin B2, and pelinin C phellinin C) includes an antioxidant composition containing one or two or more selected from among active ingredients.
또한, 본 발명의 페리너스 속(Phellinus sp.) 버섯 또는 이노노투스 속(Inonotus sp.) 버섯의 균사체 배양물로부터 얻은 3,14-비히스피디닐(3,14-bihispidinyl), 하이폴로민 B(hypholomine B), 1,1-디스티릴피릴에탄(1,1-distyrylpyrylethan), 펠리닌 A(phellinin A), 펠리닌 B(phellinin B, 펠리닌 B1↔펠리닌 B2) 및 펠리닌 C(phellinin C) 각각에 대하여 급성 독성을 시험한 결과, 50% 치사량(LD50)은 적어도 1 g/kg 이상인 것으로 나타나 매우 안전한 물질임을 알 수 있었다.In addition, 3,14-bihispidinyl, hyperpolamine obtained from the mycelium culture of the Phellinus sp . Mushroom or Inonotus sp . Mushroom of the present invention . Hypholomine B, 1,1-distyrylpyrylethan, phellinin A, phellinin B, pelinin B1↔pellin B2, and pelinin C Acute toxicity testing of each phellinin C) showed that 50% lethal dose (LD 50 ) was at least 1 g / kg, indicating a very safe substance.
본 발명의 항산화 화합물들을 의약으로 사용하는 경우에는 1 ~ 600 mg/kg을 성인에게 1일에 투여할 수 있으며, 추출물을 사용하는 경우에는 추출물을 증발시켜 그 잔사를 기준으로 10 ~ 100 mg/kg을 1회 내지 수회로 나누어 투여할 수 있다. 본 발명의 항산화 화합물에 무기 또는 유기의 담체를 가하여, 고체, 반고체 또는 액상의 형태로 경구 또는 비경구 투여할 수 있다.In case of using the antioxidant compounds of the present invention as a medicament, 1 to 600 mg / kg may be administered to adults per day, and in case of using the extract, the extract is evaporated to 10 to 100 mg / kg based on the residue. It can be administered once or divided into several times. Inorganic or organic carriers may be added to the antioxidant compounds of the present invention and administered orally or parenterally in solid, semisolid or liquid form.
경구 투여를 위한 제제로서는 정제(錠劑), 환제(丸劑), 과립제(顆粒劑), 연·경 캡슐제, 산제, 세립제, 분제, 유탁제(乳濁濟), 시럽제, 펠렛제 등을 들 수가 있다. 본 발명의 약학적 조성물은 경구 투여용 제형으로 정제 및 캡슐 등의 제형으로 제제하기 위해 락토오스, 사카로오스, 솔비톨, 만니톨, 전분, 아밀로펙틴, 셀룰로오스 또는 젤라틴과 같은 결합제; 디칼슘 포스페이트와 같은 부형제; 옥수수 전분 또는 고구마 전분과 같은 붕괴제; 스테아린산 마그네슘, 스테아린산 칼슘, 스테아릴푸마르산 나트륨 또는 폴리에틸렌글리콜 왁스와 같은 윤활유가 함유된다. 캡슐제형의 경우는 상기에서 언급한 물질 이외에도 지방유와 같은 액체 담체를 함유한다.Examples of preparations for oral administration include tablets, pills, granules, soft and hard capsules, powders, fine granules, powders, emulsions, syrups and pellets. There is a number. The pharmaceutical composition of the present invention is a formulation for oral administration, such as lactose, saccharose, sorbitol, mannitol, starch, amylopectin, cellulose or gelatin for preparation in formulations such as tablets and capsules; Excipients such as dicalcium phosphate; Disintegrants such as corn starch or sweet potato starch; Lubricants such as magnesium stearate, calcium stearate, sodium stearyl fumarate or polyethylene glycol wax. Capsules contain liquid carriers, such as fatty oils, in addition to the substances mentioned above.
비경구 투여를 위한 제재로는 주사제, 점적제, 수액(輸液), 연고, 로션, 스프레이, 현탁제, 유제(乳劑), 유제(油濟), 좌제(坐劑) 등을 들 수가 있다. 본 발명의 유효성분을 제제화하기 위해서는 상법에 따라서 실시하면 용이하게 제제화할 수 있으며, 계면활성제, 부형제, 착색료, 향신료, 보존료, 안정제, 완충제, 현탁제, 기타 상용하는 보조제를 적당히 물과 혼합하여 용액 또는 현탁액으로 제조하고 이를 앰플 또는 바이알의 단위 투여형으로 제제화하여 사용하면 된다.Preparations for parenteral administration include injections, drops, fluids, ointments, lotions, sprays, suspensions, emulsions, emulsions, suppositories, and the like. In order to formulate the active ingredient of the present invention, it can be easily formulated according to the conventional method. A surfactant, an excipient, a coloring agent, a spice, a preservative, a stabilizer, a buffer, a suspending agent, and other commonly used auxiliaries are mixed with water as appropriate. Or prepared in suspension and formulated into unit dosage forms of ampoules or vials.
이하, 실시예를 들어 본 발명을 상세히 기술할 것이나 본 발명의 범위를 이들 실시예에 의해 한정되는 것은 아니다.Hereinafter, the present invention will be described in detail with reference to Examples, but the scope of the present invention is not limited to these Examples.
실시예Example 1: One: 페리너스Perinus 속 또는 Genus or 이노노투스Innotus 속 버섯 균주의 분리 및 배양 Isolation and Culture of Genus Mushroom Strains
상황버섯(Phellinus linteus KCTC 10975BP) 균주 또는 기와층버섯(Inonotus xeranticus KCTC 10976BP) 균주 버섯 자실체를 70% 에탄올 수용액으로 표면 소독한 후 무균상자에서 멸균된 칼을 이용하여 버섯 절편을 분리한 후 포테이토-덱스트로즈 아가 배지에서 20일간 배양하여 균주를 확보하였다. 또한, 각 버섯 자실체로부터 분리한 포자를 포테이토-덱스트로즈 아가 배지 상에서 발아하여 균주를 확보할 수 있다. 확보된 균주는 포테이토-덱스트로즈를 함유한 배지를 이용하여 27 ℃에서 14일간 진탕 배양하였다. Phellinus linteus KCTC 10975BP strain or Inonotus xeranticus KCTC 10976BP strain The mushroom fruit body was surface sterilized with 70% ethanol solution, and then the mushroom slices were separated using a sterile knife in a sterile box and then potato-dex Strains were obtained by culturing in Troz agar medium for 20 days. In addition, spores isolated from each mushroom fruiting body can be germinated on potato-dextrose agar medium to secure strains. The obtained strain was shaken for 14 days at 27 ℃ using a medium containing potato-dextrose.
실시예Example 2: 버섯 균사체 추출물의 활성 2: Activity of Mushroom Mycelia Extract 분획물의Fraction 제조 Produce
상기 실시예 1의 배양물을 에틸아세테이트로 추출하고 메탄올을 사용하여 세파덱스 LH-20 컬럼 크로마토그래피를 수행하고, 다시 70% 메탄올 수용액을 사용하여 세파덱스 LH-20 컬럼 크로마토그래피를 실시하여 활성 분획물을 얻었다. The culture of Example 1 was extracted with ethyl acetate and subjected to Sephadex LH-20 column chromatography using methanol, followed by Sepadex LH-20 column chromatography using 70% aqueous methanol solution to prepare an active fraction. Got.
실시예Example 3: 3,14- 3: 3,14- 비히스피디닐(3,14-bihispidinyl)의Of bisspidinyl (3,14-bihispidinyl) 제조 Produce
상기 실시예 2에서 얻은 활성 분획물에 대하여 50% 메탄올 수용액을 사용하여 RP-TLC를 수행하여 Rf값 0.56에서 다음 화학식 4로 표시되는 3,14-비히스피디닐(3,14-bihispidinyl)를 3 mg 분리하였다. The active fraction obtained in Example 2 was subjected to RP-TLC using an aqueous 50% methanol solution to obtain 3,14-bihispidinyl (3,14-bihispidinyl) represented by the following
[화학식 4][Formula 4]
① 성상 : 노란색의 분말① Appearance: Yellow powder
② 분자량 : 490② Molecular Weight: 490
③ 분자식 : C26H18O10 ③ Molecular Formula: C 26 H 18 O 10
④ 질량분석 스펙트럼 : ESIMS m/z 489 [M-H]-, m/z 513 [M+Na]+ ④ Mass spectrometry spectrum: ESIMS m / z 489 [MH] - , m / z 513 [M + Na] +
⑤ 자외선흡수스펙트럼 : UV λmax (MeOH) 250, 373 nm⑤ UV absorption spectrum: UV λ max (MeOH) 250, 373 nm
⑥ 수소핵자기공명스펙트럼 : ppm (400MHz, CD3OD) 6.25 (s), 6.64 (d, J = 15.9 Hz), 7.36 (d, J = 15.9 Hz), 7.05 (d, J = 1.5 Hz), 6.78 (d, J = 8.4 Hz), 6.97 (dd, J = 1.5, 8.4 Hz), 6.09 (s), 6.56 (d, J = 15.9 Hz), 7.22 (d, J = 15.9 Hz), 7.23 (s), 6.66 (s) ⑥ Hydrogen nuclear magnetic resonance spectrum: ppm (400MHz, CD 3 OD) 6.25 (s), 6.64 (d, J = 15.9 Hz), 7.36 (d, J = 15.9 Hz), 7.05 (d, J = 1.5 Hz), 6.78 (d, J = 8.4 Hz), 6.97 (dd, J = 1.5, 8.4 Hz), 6.09 (s), 6.56 (d, J = 15.9 Hz), 7.22 (d, J = 15.9 Hz), 7.23 (s ), 6.66 (s)
실시예 4: 하이폴로민 B(hypholomine B)의 제조Example 4: Preparation of Hypholomine B
상기 실시예 2에서 얻은 활성 분획물에 대하여 70% 메탄올 수용액을 사용하여 RP-TLC를 실시하여 Rf값 0.4에서 다음 화학식 5로 표시되는 하이폴로민 B(hypholomine B)를 5 mg 분리하였다. 또는 고속 액체 크로마토그래 피(preparative HPLC)를 50% 메탄올(0.04% TFA)를 전개용매로 하여 체류시간 38분에서 분리할 수 있다.The active fraction obtained in Example 2 was subjected to RP-TLC using an aqueous 70% methanol solution to separate 5 mg of hypolomine B (hypholomine B) represented by the following
[화학식 5][Formula 5]
① 성상 : 노란색의 분말① Appearance: Yellow powder
② 분자량 : 490② Molecular Weight: 490
③ 분자식 : C26H18O10 ③ Molecular Formula: C 26 H 18 O 10
④ 질량분석 스펙트럼 : ESIMS m/z 513 [M+Na]+ ④ Mass Spectrometry Spectrum: ESIMS m / z 513 [M + Na] +
⑤ 자외선흡수스펙트럼 : UV λmax (MeOH) 257, 388 nm⑤ UV absorption spectrum: UV λ max (MeOH) 257, 388 nm
⑥ 수소핵자기공명스펙트럼 : ppm (500MHz, CD3OD) 4.30 (d, J = 6.4 Hz), 5.77 (d, J = 6.4 Hz), 6.08 (s), 6.40 (s), 6.67 (d, J = 16.0 Hz), 6.72 (dd, J = 2.0, 8.0 Hz), 6.78 (d, J = 8.4 Hz), 6.79 (d, J = 8.0 Hz), 6.80 (d, J = 2.0 Hz), 6.96 (d, J = 8.4, 2.0 Hz), 7.05 (d, J = 2.0 Hz), 7.38 (d, J = 16.0 Hz) ⑥ Hydrogen nuclear magnetic resonance spectrum: ppm (500MHz, CD 3 OD) 4.30 (d, J = 6.4 Hz), 5.77 (d, J = 6.4 Hz), 6.08 (s), 6.40 (s), 6.67 (d, J = 16.0 Hz), 6.72 (dd, J = 2.0, 8.0 Hz), 6.78 (d, J = 8.4 Hz), 6.79 (d, J = 8.0 Hz), 6.80 (d, J = 2.0 Hz), 6.96 (d , J = 8.4, 2.0 Hz), 7.05 (d, J = 2.0 Hz), 7.38 (d, J = 16.0 Hz)
⑦ 탄소핵자기공명스펙트럼 : ppm (100MHz, CD3OD)⑦ Carbon Magnetic Resonance Spectrum: ppm (100MHz, CD 3 OD)
162.5 (C-2), 99.7 (C-3), 174.5 (C-4), 96.0 (C-5), 165.6 (C-6), 116.9 (C-7), 138.8 (C-8), 128.6 (C-9), 115.0 (C-10). 146.8 (C-11), 149.1 (C-12), 116.9 (C-13), 122.4 (C-14), 167.8 (C-2'), 91.0 (C-3'), 173.2 (C-4'), 103.5 (C-5'), 163.6 (C-6'), 53.4 (C-7'), 92.8 (C-8'), 131.5 (C-9'), 118.9 (C-10'), 116.9 (C-11'), 147.6 (C-12'), 146.9 (C-13'), 113.8 (C-14') 162.5 (C-2), 99.7 (C-3), 174.5 (C-4), 96.0 (C-5), 165.6 (C-6), 116.9 (C-7), 138.8 (C-8), 128.6 (C-9), 115.0 (C-10). 146.8 (C-11), 149.1 (C-12), 116.9 (C-13), 122.4 (C-14), 167.8 (C-2 '), 91.0 (C-3'), 173.2 (C-4 ' ), 103.5 (C-5 '), 163.6 (C-6'), 53.4 (C-7 '), 92.8 (C-8'), 131.5 (C-9 '), 118.9 (C-10'), 116.9 (C-11 '), 147.6 (C-12'), 146.9 (C-13 '), 113.8 (C-14')
실시예 5: 1,1-디스티릴피릴에탄(1,1-distyrylpyrylethan)의 제조Example 5: Preparation of 1,1-distyrylpyrylethane
상기 실시예 2에서 얻은 활성 분획물을 90% 메탄올 수용액을 전개용매로 RP-TLC를 실시하여 Rf값 0.6에서 다음 화학식 6에 나타낸 1,1-디스티릴피릴에탄(1,1-distyrylpyrylethan)을 5 mg 분리하였다. 또는 고속 액체 크로마토그래피(preparative HPLC)를 50% 메탄올(0.04% TFA)를 전개용매로 하여 체류시간 62분에서 분리할 수 있다.The active fraction obtained in Example 2 was subjected to RP-TLC with 90% aqueous methanol solution as a developing solvent, and 5 mg of 1,1-distyrylpyrylethanol (1,1-distyrylpyrylethan) represented by the following
[화학식 6][Formula 6]
① 성상 : 노란색의 분말① Appearance: Yellow powder
② 분자량 : 518② Molecular Weight: 518
③ 분자식 : C28H22O10 ③ Molecular Formula: C 28 H 22 O 10
④ 질량분석 스펙트럼 : HRESIMS m/z 519.1287 [M+H]+ ④ Mass Spectrometry Spectrum: HRESIMS m / z 519.1287 [M + H] +
⑤ 자외선흡수스펙트럼 : UV λmax (MeOH)(logε) 253, 387 nm⑤ UV absorption spectrum: UV λ max (MeOH) (logε) 253, 387 nm
⑥ 적외선흡수스펙트럼 : IR (KBr) νmax 3430, 1650, 1550 cm-1 ⑥ Infrared Absorption Spectrum: IR (KBr) ν max 3430, 1650, 1550 cm -1
⑦ 수소핵자기공명스펙트럼 : ppm (500MHz, CD3OD) 6.13 (s), 6.51 (d, J = 16.5 Hz), 7.24 (d, J = 16.5 Hz), 7.00 (d, J = 1.8 Hz), 6.75 (d, J = 8.7 Hz), 6.89 (dd, J = 1.8, 8.7 Hz), 6.13 (s), 6.51 (d, J = 16.5 Hz), 7.24 (d, J = 16.5 Hz), 7.00 (d, J = 1.8 Hz), 6.75 (d, J = 8.7 Hz), 6.89 (dd, J = 1.8, 8.7 Hz), 4.79 (q, J = 7.6 Hz), 1.58 (d, J = 7.6 Hz) ⑦ Hydrogen nuclear magnetic resonance spectrum: ppm (500MHz, CD 3 OD) 6.13 (s), 6.51 (d, J = 16.5 Hz), 7.24 (d, J = 16.5 Hz), 7.00 (d, J = 1.8 Hz), 6.75 (d, J = 8.7 Hz), 6.89 (dd, J = 1.8, 8.7 Hz), 6.13 (s), 6.51 (d, J = 16.5 Hz), 7.24 (d, J = 16.5 Hz), 7.00 (d , J = 1.8 Hz), 6.75 (d, J = 8.7 Hz), 6.89 (dd, J = 1.8, 8.7 Hz), 4.79 (q, J = 7.6 Hz), 1.58 (d, J = 7.6 Hz)
실시예Example 6: 6: 펠리닌Pelinin A( A ( phellininphellinin A)의 제조 A) manufacture
상기 실시예 2에서 얻은 활성 분획물을 40 ~ 90%의 메탄올 수용액을 용매로 C-18 세팍 카트리지(sepak catridge)로 분획하여 90% 메탄올 용리액으로 용출된 분획에서 다음 화학식 1로 표시되는 펠리닌 A(phellinin A) 17 mg을 분리하였다[도 1, 도 2 참조]. The active fractions obtained in Example 2 were fractionated with 40 to 90% methanol aqueous solution using a solvent C-18 Sepak cartridge (sepak catridge) and eluted with 90% methanol eluent. phellinin A) 17 mg was isolated (see FIG. 1, FIG. 2).
[화학식 1][Formula 1]
① 성상 : 노란색의 분말① Appearance: Yellow powder
② 분자량 : 448② Molecular Weight: 448
③ 분자식 : C33H20O13 ③ Molecular Formula: C 33 H 20 O 13
④ 질량분석 스펙트럼 : ESIMS m/z 447 [M-H]- ④ Mass Spectrometry Spectrum: ESIMS m / z 447 [M − H] −
⑤ 자외선흡수스펙트럼 : UV λmax (MeOH) 257, 391 nm⑤ UV absorption spectrum: UV λ max (MeOH) 257, 391 nm
⑥ 적외선흡수스펙트럼 : IR (KBr) νmax 3430, 1650, 1550 cm-1 ⑥ Infrared Absorption Spectrum: IR (KBr) ν max 3430, 1650, 1550 cm -1
⑦ 수소핵자기공명스펙트럼 : ppm (400MHz, CD3OD) 6.14 (s), 6.59 (d, J = 16.0 Hz), 7.30 (d, J = 16.0 Hz), 7.02 (d, J = 2.0 Hz), 7.77 (d, J = 8.4 Hz), 6.95 (dd, J = 2.0, 8.4 Hz), 6.40 (d, J = 16.0 Hz), 5.46 (d, J = 16.0 Hz), 1.42 (s), 1.35 (m), 1.57 (m), 1.50 (m), 1.60 (m), 1.65 (m), 1.93 (m). 1.50 (m), 1.19 (m), 1.45 (m), 0.91 (s), 0.81 (s), 4.55 (m), 4.79 (m) ⑦ Hydrogen nuclear magnetic resonance spectrum: ppm (400MHz, CD 3 OD) 6.14 (s), 6.59 (d, J = 16.0 Hz), 7.30 (d, J = 16.0 Hz), 7.02 (d, J = 2.0 Hz), 7.77 (d, J = 8.4 Hz), 6.95 (dd, J = 2.0, 8.4 Hz), 6.40 (d, J = 16.0 Hz), 5.46 (d, J = 16.0 Hz), 1.42 (s), 1.35 (m ), 1.57 (m), 1.50 (m), 1.60 (m), 1.65 (m), 1.93 (m). 1.50 (m), 1.19 (m), 1.45 (m), 0.91 (s), 0.81 (s), 4.55 (m), 4.79 (m)
⑧ 탄소핵자기공명스펙트럼 : ppm (100MHz, CD3OD) 163.9 (C2), 99.4 (C3), 166.7 (C4), 101.1 (C5), 161.4 (C6), 116.8 (C7), 137.4 (C8), 128.9 (C9), 114.9 (C10), 146.8 (C11), 148.8 (C12), 116.6 (C13), 122.1 (C14), 117.4 (C1'), 125.9 (C2'), 84.5 (C3'), 41.6 (C4'), 21.5 (C5'), 55.4 (C6'), 150.4 (C7'), 33.4 (C8'), 24.7 (C9'), 37.2 (C10'), 35.8 (C11'), 28.8 (C12'), 26.7 (C13'), 110.0 (C14'), 27.8 (C15')⑧ Carbon Magnetic Resonance Spectrum: ppm (100MHz, CD 3 OD) 163.9 (C2), 99.4 (C3), 166.7 (C4), 101.1 (C5), 161.4 (C6), 116.8 (C7), 137.4 (C8), 128.9 (C9), 114.9 (C10), 146.8 (C11), 148.8 (C12), 116.6 (C13), 122.1 (C14), 117.4 (C1 '), 125.9 (C2'), 84.5 (C3 '), 41.6 ( C4 '), 21.5 (C5'), 55.4 (C6 '), 150.4 (C7'), 33.4 (C8 '), 24.7 (C9'), 37.2 (C10 '), 35.8 (C11'), 28.8 (C12 ' ), 26.7 (C13 '), 110.0 (C14'), 27.8 (C15 ')
실시예Example 7: 7: 펠리닌Pelinin B( B ( phellininphellinin B)의 제조 B) manufacture
상기 실시예 2에서 얻은 활성 분획물을 40 ~ 90%의 메탄올 수용액으로 C-18 세팍 카트리지(sepak catridge)를 사용하여 분획한 다음, 60 ~ 70%의 메탄올 수용액 분획물을 70% 메탄올 수용액으로 세파덱스 LH-20 컬럼 크로마토그래피를 실시하여 프렉션(fraction) 21-25를 농축하여 펠리닌 B(화학식 2a:펠리닌 B1↔화학식 2b:펠리닌 B2) 4 mg을 분리하였다[도 3, 도 4 참조].The active fraction obtained in Example 2 was fractionated with 40-18% aqueous methanol solution using a C-18 Sepak cartridge, and then 60-70% aqueous methanol fractions were separated with Sephadex LH with 70% aqueous methanol solution. Fraction 21-25 was concentrated by -20 column chromatography to separate 4 mg of pellinine B (Formula 2a: Pelinin B1 ↔ Formula 2b: Pelinin B2) [see FIGS. 3 and 4]. .
[화학식 2a][Formula 2a]
[화학식 2b][Formula 2b]
① 성상 : 노란색의 분말① Appearance: Yellow powder
② 분자량 : 330② Molecular Weight: 330
③ 분자식 : C18H18O6 ③ Molecular Formula: C 18 H 18 O 6
④ 질량분석 스펙트럼 : ESIMS m/z 329 [M-H]-, 353 [M+Na]+ ④ Mass Spectrometry Spectrum: ESIMS m / z 329 [MH] - , 353 [M + Na] +
⑤ 자외선흡수스펙트럼 : UV λmax (MeOH) 258, 375 nm⑤ UV absorption spectrum: UV λ max (MeOH) 258, 375 nm
⑥ 적외선흡수스펙트럼 : IR (KBr) νmax 3430, 1650, 1550 cm-1 ⑥ Infrared Absorption Spectrum: IR (KBr) ν max 3430, 1650, 1550 cm -1
⑦ 수소핵자기공명스펙트럼 : ppm (500MHz, CD3OD) 6.13 (s), 6.51 (d, J = 16.5 Hz), 7.24 (d, J = 16.5 Hz), 7.00 (d, J = 1.8 Hz), 6.75 (d, J = 8.7 Hz), 6.89 (dd, J = 1.8, 8.7 Hz), 2.81 (m), 2.15 (dd), 1.99 (dd), 1.55 (s), 1.39 (d) ⑦ Hydrogen nuclear magnetic resonance spectrum: ppm (500MHz, CD 3 OD) 6.13 (s), 6.51 (d, J = 16.5 Hz), 7.24 (d, J = 16.5 Hz), 7.00 (d, J = 1.8 Hz), 6.75 (d, J = 8.7 Hz), 6.89 (dd, J = 1.8, 8.7 Hz), 2.81 (m), 2.15 (dd), 1.99 (dd), 1.55 (s), 1.39 (d)
실시예Example 8: 8: 펠리닌Pelinin C( C ( PhellininPhellinin C)의 제조 C) manufacture
상기 실시예 2에서 얻은 활성 분획물을 40 ~ 90%의 메탄올 수용액으로 C-18 세팍 카트리지(sepak catridge)를 사용하여 분획한 다음, 60 ~ 70%의 메탄올 수용액 분획물을 70% 메탄올 수용액으로 세파덱스 LH-20 컬럼 크로마토그래피를 실시하여 프렉션(fraction) 30-34를 농축하여 다음 화학식 3으로 표시되는 펠리닌 C(Phellinin C) 3 mg을 분리하였다[도 5, 도 6 참조]. The active fraction obtained in Example 2 was fractionated with 40-18% aqueous methanol solution using a C-18 Sepak cartridge, and then 60-70% aqueous methanol fractions were separated with Sephadex LH with 70% aqueous methanol solution. Fraction 30-34 was concentrated by -20 column chromatography to separate 3 mg of pelletin C (Phellinin C) represented by the following Chemical Formula 3 (see FIGS. 5 and 6).
[화학식 3][Formula 3]
① 성상 : 노란색의 분말① Appearance: Yellow powder
② 분자량 : 344② Molecular Weight: 344
③ 분자식 : C19H20O6 ③ Molecular Formula: C 19 H 20 O 6
④ 질량분석 스펙트럼 : ESIMS m/z 343 [M-H]-, 367 [M+Na]+ ④ Mass Spectrometry Spectrum: ESIMS m / z 343 [MH] - , 367 [M + Na] +
⑤ 자외선흡수스펙트럼 : UV λmax (MeOH) 255, 381 nm⑤ UV absorption spectrum: UV λ max (MeOH) 255, 381 nm
⑥ 적외선흡수스펙트럼 : IR (KBr) νmax 3430, 1650, 1550 cm-1 ⑥ Infrared Absorption Spectrum: IR (KBr) ν max 3430, 1650, 1550 cm -1
⑦ 수소핵자기공명스펙트럼 : ppm (500MHz, CD3OD) 6.13 (s), 6.51 (d, J = 16.5 Hz), 7.24 (d, J = 16.5 Hz), 7.00 (d, J = 1.8 Hz), 6.75 (d, J = 8.7 Hz), 6.89 (dd, J = 1.8, 8.7 Hz), 2.81 (m), 2.15 (dd), 1.99 (dd), 1.55 (s), 1.39 (d) 3.28 (s) ⑦ Hydrogen nuclear magnetic resonance spectrum: ppm (500MHz, CD 3 OD) 6.13 (s), 6.51 (d, J = 16.5 Hz), 7.24 (d, J = 16.5 Hz), 7.00 (d, J = 1.8 Hz), 6.75 (d, J = 8.7 Hz), 6.89 (dd, J = 1.8, 8.7 Hz), 2.81 (m), 2.15 (dd), 1.99 (dd), 1.55 (s), 1.39 (d) 3.28 (s)
시험예Test Example 1: One: 수퍼옥사이드Superoxide 라디칼Radical 소거 효과 Elimination effect
본 화합물들의 수퍼옥사이드 라디칼 소거능을 조사하기 위하여, 96 웰 마이크로플레이트의 웰당 포타슘 포스페이트 버퍼(50 mM, pH 7.8)에 용해시킨, 크산틴(xanthine, 0.5 mM), NBT(nitrobluetetrazolium, 0.1 mM) 1:1 혼합용액 75 ㎕, DMSO(dimethylsulfoxide)에 항산화 화합물 각 농도의 시료 5 ㎕를 넣은 후 1 unit/㎖의 크산틴 옥시다아제(xanthine oxidase) 25 ㎕를 첨가하여 37 ℃에서 30분간 반응시켰다. 다음 수학식 1로부터 자유 라디칼 소거 활성(%)을 산출하였다. 양성 대조군으로는 비타민 E, 카페인산, BHA를 사용하였다. 수퍼옥사이드 라디칼 소거 활성은 시료를 넣지 않은 대조구에 비하여 흡광도 값을 50% 감소시키는 시료의 농도를 IC50으로 하여 다음 표 1에 나타내었다.To investigate the superoxide radical scavenging ability of the compounds, xanthine (0.5 mM), NBT (nitrobluetetrazolium, 0.1 mM) 1: dissolved in potassium phosphate buffer (50 mM, pH 7.8) per well of a 96 well microplate. 1 75 μl of a mixed solution and 5 μl of a sample of each concentration of an antioxidant compound were added to DMSO (dimethylsulfoxide), and then 25 μl of 1 unit / ml xanthine oxidase was added thereto, followed by reaction at 37 ° C. for 30 minutes. The free radical scavenging activity (%) was calculated from the following equation (1). As a positive control, vitamin E, caffeic acid, and BHA were used. The superoxide radical scavenging activity is shown in Table 1 below, with the concentration of IC 50 decreasing the absorbance value by 50% compared to the control without the sample.
다음 수학식 1에서 A는 본 발명의 화합물을 첨가하지 않은 시험군의 흡광도, B는 본 발명의 화합물을 첨가한 시험군의 흡광도이다.In the
시험예Test Example 2: 2: ABTSABTS 라디칼Radical 소거 효과 Elimination effect
본 화합물들의 ABTS 라디칼 소거 활성을 조사하기 위하여 95 ㎕의 ABTS 라디칼 cation 용액에 5 ㎕ 시료를 넣어 실온에서 5분간 방치 후 마이크로플레이트 리더(microplate reader)로 734 nm에서 흡광도를 측정하여 시료를 넣지 않은 대조구와 비교하였다. 농도별로 각각 활성을 측정하였으며, 50% 소거 활성을 나타내는 농도를 트롤록스(Trolox)의 상대치(TEAC, Trolox equivalen antioxidant capacity)로 다음 수학식 2에 의하여 계산하고, 양성 대조군인 카페인산, BHA와 비교하여 다음 표 1에 나타내었다.In order to investigate the ABTS radical scavenging activity of the compounds, 5 μl sample was added to 95 μl of ABTS radical cation solution, and left at room temperature for 5 minutes, and then the absorbance was measured at 734 nm using a microplate reader. Compared with. The activity was measured for each concentration, and the concentration showing 50% scavenging activity was calculated by the following equation (2) as the relative value of Trolox (Trolox equivalen antioxidant capacity), and the positive controls caffeic acid and BHA and In comparison, it is shown in Table 1 below.
시험예Test Example 3: 3: DPPHDPPH 라디칼Radical 소거 효과 Elimination effect
본 화합물들의 DPPH 라디칼 소거 활성을 측정하기 위하여, 마이크로플레이트 웰당 95 ㎕의 150 μM의 DPPH 용액과 시료 5 ㎕를 넣고 실온에서 20분간 방치한 후 마이크로플레이트 리더로 517 nm에서 흡광도를 측정하여 시료를 넣지 않은 대조구 와 비교하여 소거 활성을 나타내었다. 농도별로 각각 활성을 측정하였으며, TEAC를 상기 수학식 2에 의하여 계산하고, 양성 대조군인 카페인산, BHA와 비교하여 다음 표 1에 나타내었다.In order to measure DPPH radical scavenging activity of the compounds, 5 μl of 95 μl of 150 μM DPPH solution and 5 μl of sample per microplate well were added and allowed to stand at room temperature for 20 minutes, and then the sample was measured by measuring the absorbance at 517 nm using a microplate reader. Scavenging activity was shown in comparison with the control. The activity was measured for each concentration, and the TEAC was calculated by
상기 표 1에서 볼 수 있듯이, 본 발명에 따른 버섯 균사체 배양물로부터 분리된 항산화 화합물의 자유 라디칼 소거 활성을 조사한 결과, 화합물들은 양성 대조구인 카페이산, BHA와 비슷한 소거 활성을 나타내었다. As shown in Table 1, the free radical scavenging activity of the antioxidant compound isolated from the mushroom mycelium culture according to the present invention, the compounds showed similar scavenging activity similar to the positive control caffeic acid, BHA.
시험예Test Example 4: 4: 랫트에On the rat 대한 About 비경구투여Parenteral administration 급성 독성 시험 Acute Toxicity Test
페리너스 속 또는 이노노투스 속 버섯 균사체 배양물로부터 분리한 화학식 1 내지 6의 화합물의 급성 독성을 알아보기 위하여 다음과 같은 실험을 수행하였다.In order to determine the acute toxicity of the compounds of
6주령의 특정병원부재(SPF) SD계 랫트를 사용하여 급성독성실험을 실시하였다. 화학식 1 내지 6의 화합물 각각을 10 ml의 생리식염수에 현탁하여 1 g/kg의 용량으로 상기 랫트 2 마리의 전경골근(anterior tibialis)에 근육 내 주사 투여하였다. 시험물질 투여 후 동물의 폐사여부, 임상증상, 체중변화를 관찰하고 혈액학적 검사와 혈액 생화학적 검사를 실시하였으며, 부검하여 육안으로 복강장기와 흉강장기의 이상 여부를 관찰하였다. 시험결과, 시험물질을 투여한 모든 동물에서 특기할 만한 임상증상이나 폐사된 동물은 없었으며, 체중변화, 혈액검사, 혈액생화학 검사, 부검소견 등에서도 독성변화는 관찰되지 않았다. 이상의 결과 화학식 1 내지 6의 화합물 각각은 랫트에서 1 g/kg까지 독성변화를 나타내지 않으며 비경구 투여 최소치사량(LD50)은 1 g/kg 이상인 안전한 물질로 판단되었다.Acute toxicity test was performed using 6-week-old SPF SD rats. Each compound of
제제예 1: 시럽제의 제조Formulation Example 1 Preparation of Syrup
화학식 1 내지 6의 항산화 화합물 또는 약학적으로 허용되는 그의 염을 유효성분으로 2%(중량/부피) 함유하는 시럽은 다음과 같은 방법으로 제조하였다. A syrup containing 2% (weight / volume) of the antioxidant compound of
화학식 1 내지 6의 항산화 화합물의 산부가염, 사카린, 당을 온수 80 g에 용해시켰다. 이 용액을 냉각시킨 후, 여기에 글리세린, 사카린, 향미료, 에탄올, 소르브산 및 증류수로 이루어진 용액을 제조하여 혼합하였다. 이 혼합물에 물을 첨가하여 100 ㎖가 되게 하였다. 상기 부가염은 실시예에 의한 다른 염으로 대치시킬 수 있다.Acid addition salts, saccharin and sugars of the antioxidant compounds of
상기 시럽제의 구성성분은 다음과 같다.The components of the syrup are as follows.
유효성분 ················ 2 gActive ingredient ············· 2 g
사카린 ················ 0.8 gSaccharin 0.8 g
당 ················ 25.4 g25.4 g of sugar
글리세린 ················ 8.0 gGlycerin 8.0 g
향미료 ················ 0.04 gSpices ················ 0.04 g
에탄올 ················ 4.0 gEthanol 4.0 g
소르브산 ················ 0.4 g0.4 g of sorbic acid
증류수 ················ 정량Distilled water ··············
제제예Formulation example 2: 정제의 제조 2: preparation of tablets
화학식 1 내지 6의 항산화 화합물 또는 약학적으로 허용되는 그의 염을 유효성분으로 함유하는 정제는 다음과 같은 방법으로 제조한다.Tablets containing an antioxidant compound of
유효성분 250 g을 락토오스 175.9 g, 감자전분 180 g 및 콜로이드성 규산 32 g과 혼합하였다. 이 혼합물에 10% 젤라틴 용액을 첨가시킨 후, 분쇄해서 14 메쉬체를 통과시켰다. 이것을 건조시키고 여기에 감자전분 160 g, 활석 50 g 및 스테아린산 마그네슘 5 g을 첨가해서 얻은 혼합물을 정제로 만들었다. 250 g of active ingredient was mixed with 175.9 g of lactose, 180 g of potato starch, and 32 g of colloidal silicic acid. 10% gelatin solution was added to the mixture, which was then ground and passed through a 14 mesh sieve. It was dried and the mixture obtained by adding 160 g of potato starch, 50 g of talc and 5 g of magnesium stearate was made into a tablet.
제제예 3: 주사액제의 제조Formulation Example 3: Preparation of Injection
화학식 1 내지 6의 항산화 화합물 또는 약학적으로 허용되는 그의 염을 유효성분으로 함유하는 주사액제는 다음과 같은 방법으로 제조하였다. Injection solution containing an antioxidant compound of
유효성분 1 g, 염화나트륨 0.6 g 및 아스코르브산 0.1 g을 증류수에 용해시켜서 100 ㎖을 만들었다. 이 용액을 병에 넣고 20 ℃에서 30 분간 가열하여 멸균시켰다.1 g of the active ingredient, 0.6 g of sodium chloride and 0.1 g of ascorbic acid were dissolved in distilled water to make 100 ml. The solution was bottled and sterilized by heating at 20 ° C. for 30 minutes.
이상에서 상세히 살펴본 바와 같이, 페리너스 속 또는 이노노투스 속 버섯 균사체 배양물로부터 얻어진 상기 화합물들은 자유라디칼을 강하게 소거하는 항산화 활성이 있음을 밝히고 있어, 암을 비롯하여 동맥경화, 관절염, 뇌졸중, 파킨슨병, 알츠하이머병, 자가면역질환 등의 각종 질병에 대한 예방 및 치료와 피부 노화 억제를 위한 식품, 화장품 및 의약품의 소재로서 산업적으로 널리 이용될 수 있다.As discussed in detail above, the compounds obtained from the fungus of the genus Mushroom or genus Innotus have been shown to have an antioxidant activity that strongly eliminates free radicals, including cancer, arteriosclerosis, arthritis, stroke, Parkinson's disease. It can be widely used industrially as a material of food, cosmetics and medicines for the prevention and treatment of various diseases such as Alzheimer's disease, autoimmune diseases, and skin aging.
도 1은 펠리닌 A의 1H NMR 스펙트럼이다.1 is a 1 H NMR spectrum of fellin A. FIG.
도 2는 펠리닌 A의 13C NMR 스펙트럼이다.Figure 2 is a 13 C NMR spectrum of Felinin A.
도 3은 펠리닌 B의 1H NMR 스펙트럼이다.Figure 3 is a 1 H NMR spectrum of Felinin B.
도 4는 펠리닌 B의 13C NMR 스펙트럼이다.Figure 4 is a 13 C NMR spectrum of Felinin B.
도 5는 펠리닌 C의 1H NMR 스펙트럼이다.Figure 5 is a 1 H NMR spectrum of Felinin C.
도 6은 펠리닌 C의 1H-1H COSY 스펙트럼이다.Figure 6 is a 1 H- 1 H COSY spectrum of Felinin C.
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KR20130078395A (en) * | 2011-12-30 | 2013-07-10 | 박형진 | A composition comprising extract of a mushroom, phellinus igniarius, for prevention and treatment of multiple sclerosis and other autoimmune diseases |
KR101713166B1 (en) | 2011-12-30 | 2017-03-07 | 박형진 | A composition comprising extract of a mushroom, Phellinus igniarius, for prevention and treatment of multiple sclerosis and other autoimmune diseases |
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