KR101967173B1 - Composition comprising compounds isolated from Morus alba for preventing or treating of inflammatory disease - Google Patents
Composition comprising compounds isolated from Morus alba for preventing or treating of inflammatory disease Download PDFInfo
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- KR101967173B1 KR101967173B1 KR1020170078969A KR20170078969A KR101967173B1 KR 101967173 B1 KR101967173 B1 KR 101967173B1 KR 1020170078969 A KR1020170078969 A KR 1020170078969A KR 20170078969 A KR20170078969 A KR 20170078969A KR 101967173 B1 KR101967173 B1 KR 101967173B1
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- Prior art keywords
- compound
- composition
- mulberry
- inflammatory
- preventing
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Abstract
본 발명은 뽕나무로부터 분리된 화합물을 포함하는 염증성 질환의 예방 또는 치료용 조성물 또는 염증성 질환의 예방 또는 개선용 건강기능식품에 관한 것으로, 상기 뽕나무 유래 화합물은 NO, iNOS 및 COX-2의 생성을 저해하는 효과가 우수하여 염증성 질환의 예방 또는 치료용 조성물 또는 염증성 질환의 예방 또는 개선용 건강기능식품으로 유용하게 사용될 수 있다.The present invention relates to a composition for preventing or treating an inflammatory disease comprising a compound isolated from mulberry or a health functional food for preventing or ameliorating an inflammatory disease. The mulberry-derived compound inhibits the production of NO, iNOS and COX-2 And is useful as a composition for preventing or treating an inflammatory disease or a health functional food for preventing or ameliorating an inflammatory disease.
Description
본 발명은 뽕나무(Morus alba)로부터 분리한 화합물을 유효성분으로 포함하는 염증성 질환의 예방 또는 치료용 조성물에 관한 것이다.The invention mulberry (Morus The present invention relates to a composition for preventing or treating an inflammatory disease, which comprises a compound isolated from alba as an active ingredient.
염증 반응(inflammation)은 조직(세포)의 손상이나 외부감염원(박테리아, 곰팡이, 바이러스, 다양한 종류의 알레르기 유발물질)에 감염되었을 때, 각종 염증 매개인자 및 면역세포가 관련되어 효소의 활성화, 염증매개물질 분비, 체액 침윤, 세포 이동, 조직 파괴 등의 복합적인 생리적 반응과 홍반, 부종, 발열, 통증 등의 외적 증상을 나타낸다. 정상인 경우의 염증반응은 외부감염원을 제거하고 손상된 조직을 재생하여 생명체 기능 회복 작용을 하지만, 항원이 제거되지 않거나 내부물질이 원인이 되어 염증반응이 과도하거나 지속적으로 일어나는 경우에는 오히려 점막손상을 촉진하고, 일부에서는 류마티스 관절염, 골다공증, 패혈증, 혈관 질환, 암 등을 유도한다(Lawrence, T. et al., Nat. Rev. Immunol., 2, 787-795, 2002).Inflammation (inflammation) is caused by damage to tissues (cells) or infection with external infectious agents (bacteria, fungi, viruses, various allergens), various inflammatory mediators and immune cells are involved, Complex physiological responses such as substance secretion, fluid infiltration, cell migration, and tissue destruction, and external symptoms such as erythema, edema, fever, and pain. In the normal case, the inflammatory reaction removes the external infectious agent and regenerates the damaged tissue to regenerate the organism's function. However, when the antigen is not removed or the internal substance causes the inflammatory reaction to occur excessively or continuously, , And some induce rheumatoid arthritis, osteoporosis, sepsis, vascular disease, and cancer (Lawrence, T. et al., Nat. Rev. Immunol., 2, 787-795, 2002).
염증 반응은 상처, 미생물 감염 등에 대항하는 숙주의 방어기제에 따른 병리학적인 기작 중 가장 중요한 반응이지만, 지속적이고 과도한 염증반응은 조직을 손상시킨다. 대식세포(macrophage)는 이러한 염증 반응을 조절하는 가장 대표적인 면역세포로서, 활성화된 대식세포는 TNF-α(tumor necrosis factor-α), IL-6(interleukin-6) 및 IL-1β와 같은 다양한 염증성 매개체를 생성하고, iNOS(inducible nitric oxide synthase)와 COX-2(cyclooxygenase-2)를 합성하여 NO(nitric oxide) 및 PGE2(prostaglandin E2)를 생성한다(Jin, H. J. et al., J Ethnopharmacol., 127(3), 589-595, 2010; Laskin, D. L. et al., Annu. Rev. Pharmacol. Toxicol., 51, 267-288, 2011).Inflammatory responses are the most important pathological mechanism of host defense mechanisms against scarring, microbial infection, but persistent and excessive inflammation damage tissue. The macrophage is the most typical immune cell that regulates this inflammatory response. The activated macrophages are various inflammatory cells such as TNF-alpha (tumor necrosis factor-alpha), IL-6 (interleukin-6) And induces nitric oxide (NO) and prostaglandin E2 (PGE2) by synthesizing iNOS (inducible nitric oxide synthase) and COX-2 (cyclooxygenase-2) (Jin, HJ et al., J Ethnopharmacol. 127 (3), 589-595, 2010; Laskin, DL et al., Annu Rev. Pharmacol., Toxicol., 51, 267-288, 2011).
NO는 생리학적으로 매우 중요한 항상성 조절자이며, 장내 세균과 종양을 제거하고 혈압을 조절하거나 신경 전달을 매개하는 등의 다양한 역할을 한다. 그러나 염증이 발생하면 염증 관련 세포의 iNOS 발현량이 증가하여 다량의 NO가 생성되며, 과도하게 생성된 NO에 의해 조직 손상, 유전자 변이, 신경 손상 등이 발생하고, 혈관 투과성이 증가되어 부종이 유발된다. 염증 반응이 일어나면 대식세포의 COX-2에 의해 PGE2가 생성되는데 이것은 통증과 발열에 주로 관여하는 염증 인자이다(Wang, M. T. et al., Cancer Metastasis Rev., 26(3-4), 525-534, 2007). NO is a physiologically important homeostatic regulator and plays a variety of roles, such as eliminating intestinal bacteria and tumors, regulating blood pressure, or mediating neurotransmission. However, when inflammation occurs, the amount of iNOS expressed in the inflammation-related cells is increased to produce a large amount of NO. Excessively generated NO causes tissue damage, genetic mutation, nerve damage, and increases vascular permeability and induces edema . When inflammatory reaction occurs, PGE2 is produced by macrophage COX-2, which is an inflammatory factor mainly involved in pain and fever (Wang, MT et al., Cancer Metastasis Rev., 26 (3-4), 525-534 , 2007).
최근 질병을 예방 또는 치료할 수 있는 기능은 식품이나 식물체도 가지고 있다는 것이 보고되고 있고, 보다 건강하고 오래 살고자 하는 인류의 필요에 따라, 세계적으로 다양한 자원으로부터 다양한 생리기능을 가진 물질을 탐색하는 연구가 활발히 진행되고 있으며, 그 중에서도 특히 식물자원에 포함된 화합물에 많은 관심이 집중되고 있다(Lee, S. E. et al., J Medicinal Crop Sci., 12, 73-78, 2004).Recently, it has been reported that foods and plants have the function of preventing or treating diseases. In order to meet the needs of humans who want to live healthier and longer lives, researches to search for substances having diverse physiological functions from various resources worldwide (Lee, SE et al., J Medicinal Crop Sci., 12, 73-78, 2004).
뽕나무(Morus alba)는 쌍떡잎식물 쐐기풀목 뽕나무과 뽕나무속에 속한 낙엽 교목 또는 관목을 총칭하며, 동뽕나무, 몽고뽕나무, 꾸지뽕나무, 산뽕나무 등이 이에 속한다. 높이는 3~4미터이며, 잎은 어긋나고 끝이 뾰족한 달걀 모양인데 가장 자리에 톱니가 있다. 주로 잎은 누에의 사료로 사용하며, 나무껍질은 염료, 목재는 가구재로 사용한다. Morus alba ) are collectively termed deciduous trees or shrubs belonging to the genus Chrysanthemum bisporus and the mulberry trees of the dicotyledonous plant Nettleia, including the mulberry trees, Mongolian mulberry trees, cucumber trees and mountain mulberry trees. It is 3-4 meters high, with an oval leaf shape with a pointed end with sawtooth at its edge. Leaves are mainly used for silkworm feed, bark for wood, wood for furniture.
잎에는 플라보노이드 성분인 루틴(rutin), 퀘르세틴(quercetin), 이소퀘르세틴(isoquercetin), 모라세틴(moracetin) 등이 함유되어 있으며, 뿌리껍질에는 쿠마론 성분인 움벨리페론(umbelliferone), 스코폴레틴(scopoletin), 플라보노이드 성분인 모루신(morusin), 멀베린(mullberrin), 멀베로크로멘(mullberrochromene), 시클로멀베린(cyclomullberrin) 등이 함유되어 있으며, 상지(어린가지)에는 탄닌(tannin), 수크로스(sucrose), 프룩토스(fructose), 스타키오스(stachyose), 글루코스(glucose), 말토오스(maltose), 아라비노스(arabinose), 자일로스(xylose)와 플라보노이드 성분인 멀베린(mullberrin), 멀베로크로멘(mullberrochromene), 시클로멀베린(cyclomullberrin) 등이 함유되어있다(배기환, 한국의약용식물, 교학사, 73, 2000; 김창민 외, 중약대사전, 도서출판정담, 2824, 1998).The leaves contain rutin, quercetin, isoquercetin and moracetin, which are flavonoid components, and the root shell contains umbelliferone, umbelliferone, scopoletin), flavonoid components morusin, mullberrin, mullberrochromene and cyclomullberrin. The upper branch contains tannins, water, The present invention relates to a method for the production of a medicament for the treatment and / or prophylaxis of a disease or condition selected from the group consisting of sucrose, fructose, stachyose, glucose, maltose, arabinose, xylose and flavonoids mullberrin, Mullberrochromene, cyclomullberrin, etc. (Bae Ki-hwan, Korean Medicinal Plants, Korean Association of Pharmacists, 73, 2000; Kim Changmin et al., Chinese Medicine Dictionary, Book Publishing Agency, 2824, 1998).
뽕나무의 잎은 상엽이라 하여 발열, 감창, 두통, 해수, 각기 등의 증상에 치료 효과가 있으며, 뽕나무의 껍질은 상백피라 하여 해열, 이뇨, 소종, 기관지염의 치료 효과가 있고, 뽕나무의 어린 가지는 상지라 하여 풍으로 인한 소양증과 건조, 사지 경련, 숨이 막히는 증상 등에 치료 효과가 있다. The leaves of the mulberry are the upper leaves and have a therapeutic effect on symptoms such as fever, torture, headache, seawater and each other. The bark of mulberry is called bark bark and has the therapeutic effect of fever, diuretic, It is effective for the treatment of pruritus, dryness, cramps and breathlessness due to wind.
한편, 뽕나무 유래 화합물을 포함하는 염증성 질환의 치료용 조성물과 관련된 선행문헌으로서, 한국등록특허 제10-1672138호에는 꾸지뽕나무로부터 분리된 쿠드라플라바논 D 또는 스텝포제닌을 유효성분으로 포함하는 염증성 질환의 예방 및 치료용 조성물을 개시하였으며, 한국등록특허 제10-1438543호에는 항염증, 항노화 기능성 옥시레스베라트롤, 트란스-레스베라트롤 및 모라신이 함유된 뽕나무 가지추출물의 제조방법을 개시하였고, 한국등록특허 제10-1223146호에는 뽕나무 추출물을 활용한 알레르기 및 대장염증 질환 치료 효능을 가지는 약학적 조성물 및 기능성 식품 조성물을 개시하였다. 그러나, 본 발명의 뽕나무 잎 유래 화합물인 10-옥소모르니그롤 F, 6-게라닌 아피게닌 및 멀베라놀이 염증성 질환에 대한 치료 효과가 있음을 확인한 이전 보고는 아직 없다. On the other hand, as a prior art related to a composition for the treatment of inflammatory diseases including mulberry-derived compounds, Korean Patent Registration No. 10-1672138 discloses a composition for treating inflammatory diseases including inflammatory diseases including curdraplavanone D or stepogenin, Korean Patent No. 10-1438543 discloses a method for producing an extract of mulberry tree containing anti-inflammatory, anti-aging functional oxiresveratrol, trans-resveratrol and morasin, 10-1223146 discloses a pharmaceutical composition and a functional food composition having an effect of treating allergies and inflammatory diseases of the colon using mulberry extract. However, there is no previous report confirming the therapeutic effect of the mulberry leaf-derived compounds of the present invention, 10-oxomoroniglore F, 6-galanin apigenin and mulberolone in inflammatory diseases.
본 발명의 목적은 뽕나무(Morus alba)로부터 분리한 화합물의 NO, iNOS, COX-2의 생성 저해 효과를 통해 염증성 질환의 예방 또는 치료용 조성물 또는 염증성 질환의 예방 또는 개선용 건강기능식품을 제공하는 데에 있다.An object of the present invention is mulberry (Morus alba ), the composition for preventing or treating an inflammatory disease or the health functional food for preventing or ameliorating an inflammatory disease through the inhibitory effect on the formation of NO, iNOS and COX-2.
본 발명은 뽕나무(Morus alba)로부터 분리한 하기 화학식 1의 10-옥소모르니그롤 F(화합물 1), 6-게라닌 아피게닌(화합물 2) 및 멀베라놀(화합물 3)로 이루어진 군에서 선택되는 1종 이상의 화합물을 유효성분으로 포함하는 것을 특징으로 하는 염증성 질환의 예방 또는 치료용 약학 조성물에 관한 것으로, 상기 염증성 질환은 알레르기성 질환, 염증성 장질환, 전신성 홍반성낭창, 염증성 콜라겐 혈관 질환, 사구체신염, 염증성 피부 질환, 유육종증, 망막염, 위염, 간염, 장염, 관절염, 편도선염, 인후염, 기관지염, 폐렴, 췌장염, 패혈증 및 신장염으로 이루어진 군에서 선택되는 질환이다. The invention mulberry (Morus alba) to a separation in case of 10-oxo formula (I) from geurol F (Compound 1), 6-Guerra non Bahia genin (Compound 2) and far vera play (Compound 3) is valid for at least one compound selected from the group consisting of Wherein the inflammatory disease is selected from the group consisting of allergic diseases, inflammatory bowel disease, systemic lupus erythematosus, inflammatory collagen vascular disease, glomerulonephritis, inflammatory skin diseases, Sarcoidosis, retinitis, gastritis, hepatitis, enteritis, arthritis, tonsillitis, sore throat, bronchitis, pneumonia, pancreatitis, sepsis and nephritis.
[화학식 1][Chemical Formula 1]
상기 10-옥소모르니그롤 F(화합물 1), 6-게라닌 아피게닌(화합물 2) 및 멀베라놀(화합물 3)은, 뽕나무 추출물로부터 얻을 수 있으며, 상기 뽕나무 추출물은 뽕나무의 가지, 잎, 꽃, 뿌리, 열매 등의 뽕나무 유래의 모든 것을 이용하여 제조할 수 있으나, 뽕나무의 가지를 사용하는 것이 바람직하다. The 10-oxomonoglycol F (compound 1), 6-geranin apigenin (compound 2) and mulberanol (compound 3) can be obtained from the mulberry extract, and the mulberry extract can be obtained from the branches, leaves, , Root, fruit, etc., but it is preferable to use branches of mulberry.
또한, 상기 뽕나무 추출물은 뽕나무의 가지 또는 줄기를 C1 내지 C4의 알코올 또는 이들의 혼합용액을 용매로 하여 추출할 수 있으며, 상기 C1 내지 C4의 알코올은 메탄올, 에탄올, 프로판올, 이소프로판올, 부탄올 및 이소부탄올로 이루어진 군에서 선택될 수 있다. In addition, the mulberry extract may be extracted from the branches or stems of mulberry with a C1 to C4 alcohol or a mixed solution thereof as a solvent. The C1 to C4 alcohols may be extracted from methanol, ethanol, propanol, isopropanol, butanol and isobutanol ≪ / RTI >
상기 뽕나무 추출물로부터 화합물 1 내지 3을 추출하기 위해서는 당분야의 통상적인 방법으로서 상기 뽕나무의 물, C1 내지 C4의 알코올 또는 이들의 혼합용액 추출물을 물에 녹인 후에 유기용매로 재분획한 분획물일 수 있다. 상기 유기용매로는 n-헥산, 에틸아세테이트 및 n-부탄올 등을 사용할 수 있으며, 상기 유기용매를 1종 이상 선택하여 추가적으로 분획하거나, 또는, 상기 유기용매를 조합하여 순차적으로 분획한 다음, 크로마토그래피를 이용하여 정제할 수 있다. 또한, 상기 추출물 또는 이의 분획물의 추출시간은 특별히 제한되는 것은 아니나, 10분 내지 1일 이내에 추출하는 것이 바람직하며, 추출용 기기로는 통상의 추출기기, 초음파분쇄추출기 또는 분획기를 이용할 수 있다. In order to extract the compounds 1 to 3 from the mulberry extract, it may be a fraction obtained by dissolving the water of mulberry, the alcohol of C1 to C4 or a mixed solution thereof in water, and then fractionating it with an organic solvent . As the organic solvent, n-hexane, ethyl acetate, n-butanol, etc. may be used. One or more kinds of the organic solvent may be selected and further fractionated, or the organic solvent may be sequentially combined, And the like. The extraction time of the extract or the fraction thereof is not particularly limited, but it is preferably extracted within 10 minutes to 1 day. As the extraction apparatus, a conventional extraction apparatus, an ultrasonic pulverization extractor, or a fractionator may be used.
한편, 상기 뽕나무 추출물을 상법에 따라, 유기용매(알코올, 에테르, 아세톤 등)에 의한 추출, 헥산과 물의 분배, 크로마토그래피에 의한 방법 등, 식물체 성분의 분리 추출에 이용되는 공지의 방법을 단독 또는 적합하게 조합한 방법을 이용하여 분획 또는 정제함으로서 본 발명의 화합물 1 내지 3을 얻을 수 있다. On the other hand, the known method used for the separation and extraction of plant components, such as extraction with an organic solvent (alcohol, ether, acetone, etc.), distribution of hexane and water, The compounds 1 to 3 of the present invention can be obtained by fractionation or purification using a suitably combined method.
상기 크로마토그래피는 실리카겔 컬럼 크로마토그래피(silica gel column chromatography), HP-20 컬럼 크로마토그래피(HP-20 column chromatography), LH-20 컬럼 크로마토그래피(LH-20 column chromatography), RP-18 컬럼 크로마토그래피(RP-18 column chromatography), 이온교환수지 크로마토그래피(ion exchange resin chromatography), 중압 액체 크로마토그래피(medium pressure liquid chromatography), 박층 크로마토그래피(thin layer chromatography), 실리카겔 진공 액체 크로마토그래피(silica gel vacuum liquid chromatography) 및 고성능 액체 크로마토그래피(high performance liquid chromatography) 등에서 선택하여 사용할 수 있다.The above chromatography was carried out by silica gel column chromatography, HP-20 column chromatography, LH-20 column chromatography, RP-18 column chromatography RP-18 column chromatography, ion exchange resin chromatography, medium pressure liquid chromatography, thin layer chromatography, silica gel vacuum liquid chromatography ) And high-performance liquid chromatography (HPLC).
한편, 본 발명의 화합물은 당해 기술 분야에서 통상적인 방법에 따라 합성될 수 있으며, 약학적으로 허용 가능한 염으로 제조될 수도 있다.Meanwhile, the compound of the present invention can be synthesized according to a conventional method in the art, and can also be prepared as a pharmaceutically acceptable salt.
본 발명에 따른 약학 조성물은 일반적으로 사용되는 약학적으로 허용 가능한 담체와 함께 적합한 형태로 제형화될 수 있다. 약학적으로 허용 가능이란 생리학적으로 허용되고 인간에게 투여될 때, 통상적으로 위장 장애, 현기증 등과 같은 알레르기 반응 또는 이와 유사한 반응을 일으키지 않는 조성물을 말한다. The pharmaceutical composition according to the present invention can be formulated into a suitable form together with a commonly used pharmaceutically acceptable carrier. Pharmaceutically acceptable means a composition that is physiologically acceptable and does not normally cause an allergic reaction such as gastrointestinal disorder, dizziness, or the like when administered to humans, or a similar reaction.
또한, 상기 약학 조성물은 각각 통상의 방법에 따라 산제, 과립제, 정제, 캡슐제, 현탁액, 에멀젼, 시럽, 에어로졸 등의 경구형 제형, 외용제, 좌제 및 멸균 주사용액의 형태로 제형화하여 사용될 수 있다. 상기 약학 조성물에 포함될 수 있는 담체, 부형제 및 희석제로는 락토오스, 덱스트로즈, 수크로스, 소르비톨, 만니톨, 자일리톨, 에리스리톨, 말티톨, 전분, 아라비아 고무, 알지네이트, 젤라틴, 칼슘 포스페이트, 칼슘 실리케이트, 셀룰로오스, 메틸 셀룰로오스, 미결정셀룰로오스, 폴리비닐 피롤리돈, 물, 파라옥시벤조산메틸, 파라옥시벤조산프로필, 탈크, 스테아르산마그네슘 및 광물유를 포함할 수 있으나, 이에 한정되는 것은 아니다. 제제화할 경우에는 보통 사용하는 충진제, 안정화제, 결합제, 붕해제, 계면활성제 등의 희석제 또는 부형제를 사용하여 조제된다. 경구투여를 위한 고형제제에는 정제, 환제, 산제, 과립제, 캡슐제 등이 포함되며, 이러한 고형제제는 본 발명의 화합물에 적어도 하나 이상의 부형제, 예를 들면, 전분, 탄산칼슘, 수크로스 또는 락토오스, 젤라틴 등을 섞어 조제된다. 또한 단순한 부형제 이외에 마그네슘 스테아레이트, 탈크 같은 윤활제들도 사용된다. 경구를 위한 액상 제제로는 현탁제, 내용액제, 유제, 시럽제 등이 해당되는데 흔히 사용되는 단순희석제인 물, 리퀴드 파라핀 이외에 여러 가지 부형제, 예를 들면 습윤제, 감미제, 방향제, 보존제 등이 포함될 수 있다. 비경구 투여를 위한 제제에는 멸균된 수용액, 비수성용제, 현탁제, 유제, 동결건조 제제, 좌제가 포함된다. 비수성용제, 현탁제로는 프로필렌글리콜, 폴리에틸렌글리콜, 올리브 오일과 같은 식물성 기름, 에틸올레이트와 같은 주사 가능한 에스테르 등이 사용될 수 있다. 좌제의 기제로는 위텝솔(witepsol), 마크로골, 트윈(tween) 61, 카카오지, 라우린지, 글리세로제라틴 등이 사용될 수 있다. The pharmaceutical compositions may be formulated in the form of powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols and the like, external preparations, suppositories and sterilized injection solutions according to a conventional method . Examples of carriers, excipients and diluents that can be contained in the pharmaceutical composition include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, gum arabic, alginate, gelatin, calcium phosphate, calcium silicate, But are not limited to, methylcellulose, microcrystalline cellulose, polyvinylpyrrolidone, water, methyl paraoxybenzoate, propylparaxybenzoate, talc, magnesium stearate and mineral oil. In the case of formulation, it is prepared using diluents or excipients such as fillers, stabilizers, binders, disintegrants, surfactants and the like which are usually used. Solid formulations for oral administration include tablets, pills, powders, granules, capsules and the like, which may contain at least one excipient, such as starch, calcium carbonate, sucrose or lactose, Gelatin and the like. In addition to simple excipients, lubricants such as magnesium stearate and talc are also used. Examples of the liquid preparation for oral use include suspensions, solutions, emulsions, and syrups. In addition to water and liquid paraffin, simple diluents commonly used, various excipients such as wetting agents, sweeteners, fragrances, preservatives and the like may be included . Formulations for parenteral administration include sterilized aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations, and suppositories. Examples of the suspending agent include propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate, and the like. Examples of the suppository base include witepsol, macrogol, tween 61, cacao butter, laurin, glycerogelatin and the like.
본 발명에 개시된 화학식 1의 화합물을 유효성분으로 포함하는 약학 조성물은 쥐, 가축, 인간 등의 포유동물에 다양한 경로로 투여될 수 있다. 투여의 모든 방식은 예상될 수 있는데, 예를 들면, 경구, 직장 또는 정맥, 근육, 피하, 자궁내 경막 또는 뇌혈관내 주사에 의해 투여될 수 있다. 투여량은 치료받을 대상의 연령, 성별, 체중, 치료할 특정 질환 또는 병리 상태, 질환 또는 병리 상태의 심각도, 투여시간, 투여경로, 약물의 흡수, 분포 및 배설률, 사용되는 다른 약물의 종류 및 처방자의 판단 등에 따라 달라질 것이다. 이러한 인자에 기초한 투여량 결정은 당업자의 수준 내에 있으며, 일반적으로 투여량은 0.01㎎/㎏/일 내지 대략 2000㎎/㎏/일의 범위이다. 더 바람직한 투여량은 1㎎/㎏/일 내지 500㎎/㎏/일이다. 투여는 하루에 한번 투여할 수도 있고, 수회 나누어 투여할 수 있다. 상기 투여량은 어떠한 면으로든 본 발명의 범위를 한정하는 것은 아니다. The pharmaceutical composition comprising the compound of formula (I) as an active ingredient of the present invention can be administered to mammals such as rats, livestock, and humans in various routes. All modes of administration may be expected, for example, by oral, rectal or intravenous, intramuscular, subcutaneous, intra-uterine dural or intracerebral injection. The dosage will depend on the age, sex, body weight, the particular disease or condition being treated, the severity of the disease or condition, the time of administration, the route of administration, the absorption, distribution and excretion of the drug, It depends on judgment. Dosage determinations based on these factors are within the level of ordinary skill in the art and generally the dosage ranges from 0.01 mg / kg / day to approximately 2000 mg / kg / day. A more preferable dosage is 1 mg / kg / day to 500 mg / kg / day. The administration may be carried out once a day or divided into several doses. The dose is not intended to limit the scope of the invention in any way.
또한, 본 발명은 뽕나무로부터 분리한 상기 화학식 1의 화합물 군에서 선택되는 1종 이상의 화합물 및 식품학적으로 허용 가능한 식품보조 첨가제를 포함하는 염증성 질환의 예방 또는 개선용 건강기능식품을 제공한다. The present invention also provides a health functional food for preventing or ameliorating an inflammatory disease comprising at least one compound selected from the group of compounds of the formula (1) isolated from mulberry and a pharmaceutically acceptable food-aid additive.
상기 화합물은 본 발명의 건강기능식품에 0.001~50 중량%로 하여 첨가될 수 있다. 본 발명의 건강기능식품은 정제, 캡슐제, 환제 또는 액제 등의 형태를 포함하며, 본 발명의 화합물을 첨가할 수 있는 식품으로는, 예를 들어, 각종 식품류, 음료, 껌, 차, 비타민 복합제 등이 있다.The compound may be added to the health functional food of the present invention in an amount of 0.001 to 50% by weight. The health functional food of the present invention includes forms such as tablets, capsules, pills, and liquids, and examples of foods to which the compound of the present invention can be added include various foods, beverages, gums, tea, vitamins .
또 다른 일면에 있어서, 본 발명은 하기 화학식 2의 신규 화합물 10-옥소모르니그롤 F(화합물 1)를 제공한다.In another aspect, the present invention provides a novel compound 10-oxomonoglycol F (compound 1) of the following formula 2:
[화학식 2](2)
본 발명은 뽕나무로부터 분리된 화합물을 포함하는 염증성 질환의 예방 또는 치료용 조성물 또는 염증성 질환의 예방 또는 개선용 건강기능식품에 관한 것으로, 상기 뽕나무 유래 화합물은 NO, iNOS 및 COX-2의 생성을 저해하는 효과가 우수하여 염증성 질환의 예방 또는 치료용 조성물 또는 염증성 질환의 예방 또는 개선용 건강기능식품으로 유용하게 사용될 수 있다.The present invention relates to a composition for preventing or treating an inflammatory disease comprising a compound isolated from mulberry or a health functional food for preventing or ameliorating an inflammatory disease. The mulberry-derived compound inhibits the production of NO, iNOS and COX-2 And is useful as a composition for preventing or treating an inflammatory disease or a health functional food for preventing or ameliorating an inflammatory disease.
도 1은 본 발명의 화합물 1 내지 3이 농도 의존적으로 iNOS 및 COX-2의 생성을 저해하는 효과가 있음을 확인한 결과이다. 1 shows the results of confirming that the compounds 1 to 3 of the present invention have an effect of inhibiting the production of iNOS and COX-2 in a concentration-dependent manner.
이하 본 발명의 바람직한 실시예를 상세히 설명하기로 한다. 그러나 본 발명은 여기서 설명되는 실시예에 한정되지 않고 다른 형태로 구체화될 수도 있다. 오히려, 여기서 소개되는 내용이 철저하고 완전해지고, 당업자에게 본 발명의 사상을 충분히 전달하기 위해 제공하는 것이다. Hereinafter, preferred embodiments of the present invention will be described in detail. However, the present invention is not limited to the embodiments described herein but may be embodied in other forms. Rather, the intention is to provide an exhaustive, complete, and complete disclosure of the principles of the invention to those skilled in the art.
<< 실시예Example 1. 뽕나무 유래 화합물의 분리> 1. Isolation of mulberry-derived compounds>
본 발명에서 사용된 뽕나무(Morus alba L.)의 건조된 가지는 대구 약령시 한약재도매시장에서 구입하였다. The mulberry ( Morus alba L.) was purchased from the wholesale market of medicinal herbs in Daegu.
건조된 뽕나무 가지 9.8㎏을 20ℓ 메탄올(3회×20ℓ)로 추출하고, 상기 과정에서 얻은 메탄올 추출액을 감압 농축하여 용매를 제거함으로써 710g의 메탄올 추출물을 얻었다. 이후, 상기 메탄올 추출물에 물 4ℓ로 현탁한 다음, n-헥산(5ℓ×3회), 에틸아세테이트(5ℓ×3회) 및 n-부탄올(5ℓ×3회)로 순차적으로 분획하여 n-헥산 분획물(140.7g), 에틸아세테이트 분획물(123.8g) 및 n-부탄올 분획물(70g)과 마지막으로 물 분획물(365.5g)을 얻었다.9.8 kg of dried mulberry branches were extracted with 20 L of methanol (3 times 20 L), and the methanol extract obtained in the above procedure was concentrated under reduced pressure to remove the solvent, thereby obtaining 710 g of methanol extract. Then, the methanol extract was suspended in 4 L of water and then sequentially fractionated with n-hexane (5
상기 분획물 중 에틸아세테이트 분획물을 클로로포름:메탄올(50:1 to 0:1, each 10ℓ)의 농도구배 용출 조건에 따른 크로마토그래피(컬럼크기: 80×12㎝, 입자크기: 63-200㎛, Merck)로 분획하여 TLC 패턴에 따른 12개의 소분획물(Fr.1~12)을 얻었다. The ethyl acetate fraction in the fractions was subjected to chromatography (column size: 80 × 12 cm, particle size: 63-200 μm, Merck) according to concentration gradient elution conditions of chloroform: methanol (50: 1 to 0: To obtain 12 small fractions (Fr.1 to 12) according to the TLC pattern.
상기 12개의 소분획물 중 Fr.10(22.0g)을 이용하여, 헥산:에틸아세테이트(4:1)의 용출 조건으로 실리카겔 컬럼 크로마토그래피(컬럼크기: 60×6.5㎝)하여 4개의 소분획물(Fr.10-1~10-4)을 얻었다. 또한, 상기 4개의 소분획물 중 Fr.10-3을 헥산:아세톤(6:1 to 0:1)의 농도구배 용출 조건에 따른 실리카겔 컬럼 크로마토그래피(컬럼크기: 60×3.5㎝)하여 본 발명의 화합물 1(20㎎) 및 2(3㎎)를 얻었다.Four small fractions Fr (10.0 g) were fractionated on silica gel column chromatography (column size: 60 x 6.5 cm) using elution conditions of hexane: ethyl acetate (4: 1) . 10-1 to 10-4) were obtained. Of the four small fractions, Fr.10-3 was subjected to silica gel column chromatography (column size: 60 x 3.5 cm) according to a gradient elution gradient of hexane: acetone (6: 1 to 0: 1) Compound 1 (20 mg) and 2 (3 mg) were obtained.
다음으로, 상기 12개의 소분획물 중 Fr.8을 헥산:아세톤(5:1 to 0:1)의 농도구배 용출 조건에 따른 실리카겔 컬럼 크로마토그래피(컬럼크기: 60×3.5㎝)하여 본 발명의 화합물 3(20㎎)을 얻었다.Next, among the 12 small fractions, Fr.8 was subjected to silica gel column chromatography (column size: 60 x 3.5 cm) according to a concentration gradient elution gradient of hexane: acetone (5: 1 to 0: 1) 3 (20 mg).
상기 과정을 통해 얻은 화합물 1 내지 3의 물리화학적 특성은 하기 기재된 바와 같다.The physicochemical properties of the compounds 1 to 3 obtained through the above process are as described below.
화합물 1. 10-Compound 1. 10- 옥소모르니그롤Oxomonoglycol F F
10-oxomornigrol F;10-oxomorphol F;
노란 비결정 분말; Yellow amorphous powder;
UV λ max (acetone) 335nm;UV ? Max (acetone) 335 nm;
IR (KBr) νmax 3329 (OH), 1743 (CO), 1448, 1111 cm-1;IR (KBr)? Max 3329 (OH), 1743 (CO), 1448, 1111 cm -1 ;
1H 및 13C NMR(CD3OCD3) 데이터는 하기 표 1 참고; 1 H and 13 C NMR (CD 3 OCD 3 ) data are shown in Table 1 below;
HRESIMS m/z 459.1418 [M+Na]+ (calcd for C25H24O7Na, 459.1420). HRESIMS m / z 459.1418 [M + Na] + (calcd for C 25 H 24 O 7 Na, 459.1420).
화합물 2. 6-
6-geranin apigenin;6-geranin apigenin;
노란 비결정 분말;Yellow amorphous powder;
1H 및 13C NMR(CD3OCD3) 데이터는 하기 표 2 참고; 1 H and 13 C NMR (CD 3 OCD 3 ) data are shown in Table 2 below;
b Overlapped with other signal a 1 H-NMR (400 MHz) and 13 C-NMR (100 MHz): in CD 3 OCD 3
b Overlapped with other signal
화합물 3.
mulberranol;mulberranol;
노란 비결정 분말;Yellow amorphous powder;
1H 및 13C NMR(CD3OCD3) 데이터는 하기 표 3 참고; 1 H and 13 C NMR (CD 3 OCD 3 ) data are shown in Table 3 below;
b Overlapped with other signal a 1 H-NMR (400 MHz) and 13 C-NMR (100 MHz): in CD 3 OCD 3
b Overlapped with other signal
<< 실험예Experimental Example 1. 세포 배양> 1. Cell culture>
본 발명의 뽕나무로부터 분리된 화합물에 대한 항염증 활성을 측정하기 위해 사용된 세포의 배양 조건은 하기와 같다. The culture conditions of the cells used for measuring the anti-inflammatory activity of the compound isolated from mulberry of the present invention are as follows.
마우스 대식세포인 RAW 264.7 세포를 10% FBS(fetal bovine serum, heat-inactivated), 페니실린(100units/㎖), 스트렙토마이신(100㎍/㎖)이 포함된 DMEM(Dulbecco's Modified Essential Medium) 배지에서 37℃, 5% CO2의 습윤 조건으로 배양하였다. 이후, 상기 배양된 세포에 본 발명의 화합물 1 내지 3을 0~10㎍/㎖의 농도로 첨가하여 4시간 동안 사전 배양하였다. Mouse macrophages RAW 264.7 cells were cultured in DMEM (Dulbecco's Modified Essential Medium) medium containing 10% FBS (fetal bovine serum, heat-inactivated), penicillin (100 units / ml) and streptomycin , And 5% CO 2 . Then, the compounds 1 to 3 of the present invention were added to the cultured cells at a concentration of 0 to 10 μg / ml and preincubated for 4 hours.
<< 실험예Experimental Example 2. 세포생존율 확인- 2. Identification of cell viability - MTTMTT assay> assay>
상기 실험예 1에서, 본 발명의 화합물 1 내지 3(0.5-25μM) 또는 대조군(무처리군)이 처리되어 배양된 RAW 264.7 세포(1×105 cells/㎖)에 1㎍/㎖ 농도의 LPS(Sigma Chemical Co., St. Louis, MO)를 처리하거나 또는 무처리한 다음, 24시간 동안 배양하였다. 이후, 배양액에 MTT 시약 50㎕를 더한 뒤, 37℃에서 4시간 동안 추가 반응하였다. 상기 과정을 통해 생성된 포마잔 결정(formazan crystal)은 DMSO에 녹여 570㎚에서의 흡광도를 측정하였으며, 이때, LPS를 처리한 대조군(무처리군)을 100%로 하고, 하기 수식으로 계산하여 표 4에 나타내었다. In Experimental Example 1, RAW 264.7 cells (1 × 10 5 cells / ml) treated with the compounds of the present invention 1 to 3 (0.5 to 25 μM) or the control group (untreated group) (Sigma Chemical Co., St. Louis, MO) were treated or not treated and then cultured for 24 hours. Then, 50 μl of the MTT reagent was added to the culture, followed by further reaction at 37 ° C for 4 hours . The formazan crystal produced in the above procedure was dissolved in DMSO and the absorbance at 570 nm was measured. At this time, the control group (untreated group) treated with LPS was determined as 100% Respectively.
[수식][Equation]
상기 표 4를 참고하면, 뽕나무로부터 분리한 본 발명의 화합물 1 내지 3의 세포생존율이 90% 이상으로 나타나, 대식세포에 세포독성을 나타내지 않는 것임을 확인할 수 있었다. Referring to Table 4, it was confirmed that the cell survival rate of the compounds 1 to 3 of the present invention isolated from mulberry was 90% or more, indicating no cytotoxicity to macrophages.
<< 실험예Experimental Example 3. NO 생성 저해 확인> 3. Confirmation of inhibition of NO production>
RAW 264.7 세포의 상등액을 이용하여 아질산염(nitrite)을 측정하고, 이로부터 NO 생성량을 분석하여, 본 발명의 화합물이 NO 생성에 미치는 영향을 확인하였다.Nitrite was measured using a supernatant of RAW 264.7 cells and the amount of NO produced was analyzed to determine the effect of the compound of the present invention on NO production.
상기 실험예 1에서, 본 발명의 화합물 1 내지 3(0-25μM) 또는 양성대조군(celastrol)이 처리되어 배양된 RAW 264.7 세포(1×105 cells/㎖)에 1㎍/㎖ 농도의 LPS(Sigma Chemical Co., St. Louis, MO)로 처리하거나 또는 무처리한 다음, 24시간 동안 배양하였다. 이후, 세포 배양액의 상등액(100㎕)과 그리스 시약(100㎕)을 혼합하여 570㎚에서의 흡광도를 측정한 다음, 이로부터 NO 생성 저해 활성을 분석하여 표 5에 나타내었다.In Experimental Example 1, RAW 264.7 cells (1 × 10 5 cells / ml) treated with the compounds of the present invention 1 to 3 (0-25 μM) or a positive control (celastrol) Sigma Chemical Co., St. Louis, MO) or untreated and then cultured for 24 hours. Thereafter, the supernatant (100 μl) of the cell culture broth and the grease reagent (100 μl) were mixed and the absorbance at 570 nm was measured. From this, the NO production inhibitory activity was analyzed and shown in Table 5.
상기 표 5의 결과를 참고하면, 염증이 유발된 대식세포에 본 발명의 화합물 1 내지 3을 처리하는 경우, NO의 생성을 저해하는 활성이 우수함을 확인할 수 있었다.Referring to the results shown in Table 5, it was confirmed that when the compounds of the present invention 1 to 3 were treated with inflammation-induced macrophages, the activity of inhibiting NO production was excellent.
<< 실험예Experimental Example 4. 4. 웨스턴Western 블랏Blat 분석(Western blot analysis)> Western blot analysis>
상기 실험예 1의 조건으로 배양된 RAW 264.7 세포에 차가운 세포 파쇄 용액(50mM Tris-HCl, pH 7.5, 1% Nonidet P-40, 1mM EDTA, 1mM phenylmethylsulfonyl fluoride, 1㎍/㎖ leupeptin, 1mM sodium vanadate, 150mM NaCl)을 더하여 단백질을 추출하였으며, 상기 과정에서 추출된 단백질 50㎍을 취하여 SDS-PAGE(sodium dodecyl sulfatepolyacrylamide gel electrophoresis)를 실시한뒤, PVDF(polyvinylidene difluoride membrane, Millipore, Bedford, MA, USA)에 전이하였다. 상기 멤브레인을 5% 탈지유(skim milk)로 블록킹(blocking)한 후, 1차 항체(iNOS 및 COX-2, Santa Cruz, CA, USA; α-tubulin, Sigma) 반응을 진행하였다. 이후, HRP(horseradish peroxidase)가 포함된 2차 항체로 반응한 뒤, ECL 시약(enhanced chemiluminescence, Amersham Pharmacia Biotec, Buckinghamshire, UK)을 첨가하여 단백질이 전이된 멤브레인의 분석을 실시하여 도 1에 나타내었다.To the RAW 264.7 cells cultured under the conditions of Experimental Example 1, cold cell disruption solution (50 mM Tris-HCl, pH 7.5, 1% Nonidet P-40, 1 mM EDTA, 1 mM phenylmethylsulfonyl fluoride, 1 μg / ml leupeptin, 1 mM sodium vanadate, Protein was extracted by adding 150mM NaCl and subjected to sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) using 50 μg of the extracted protein. Then, PVDF (polyvinylidene difluoride membrane, Millipore, Bedford, Mass., USA) Respectively. The membrane was blocked with 5% skim milk and reacted with primary antibodies (iNOS and COX-2, Santa Cruz, CA, USA; α-tubulin, Sigma). After the reaction with a secondary antibody containing HRP (horseradish peroxidase), an ECL reagent (enhanced chemiluminescence, Amersham Pharmacia Biotec, Buckinghamshire, UK) was added to analyze the protein-transferred membrane. .
도 1의 결과를 참고하면, LPS가 처리된 대식세포에 본 발명의 화합물을 처리하는 경우, 염증 관련 인자인 iNOS 및 COX-2의 발현을 농도 의존적으로 저해하여, 염증성 질환의 예방 또는 치료용 조성물로 유용하게 사용될 수 있음을 확인할 수 있었다.1, when the compound of the present invention is treated on macrophages treated with LPS, the expression of iNOS and COX-2, which are inflammation-related factors, is inhibited in a concentration-dependent manner, and a composition for preventing or treating inflammatory diseases It can be used effectively.
<< 실험예Experimental Example 5. 독성실험> 5. Toxicity test>
실험예Experimental Example 5-1. 급성독성 5-1. Acute toxicity
본 발명의 화합물 1 또는 3을 단기간에 과량을 섭취하였을 시 급성적(24시간 이내)으로 동물체내에 미치는 독성을 조사하고, 치사율을 결정하기 위하여 본 실험을 수행하였다. 일반적인 마우스인 ICR 마우스 계통 20마리를 대조군은 10마리, 실험군은 10마리씩 배정하였다. 대조군에는 아무것도 투여하지 않았으며, 실험군은 본 발명의 화합물 1 또는 3을 2.0g/㎏(일반적인 동물실험에서 사용되는 양의 50배 정도)의 농도로 경구 투여하였다. 투여 24시간 후에 각각의 치사율을 조사한 결과, 대조군과 2.0g/㎏ 농도의 본 발명의 화합물 1 또는 3을 투여한 실험군은 모두 생존하였다. This experiment was conducted to investigate the toxicity of the compound of the
실험예Experimental Example 5-2. 5-2. 실험군Experimental group 및 대조군의 장기 및 조직 독성 실험 And control organ organs and tissue toxicity experiments
C57BL/6J 생쥐를 대상으로 동물의 각 장기(조직)에 미치는 영향을 조사하기 위하여 본 발명의 화합물 1 또는 3을 투여한 실험군과 용매만을 투여한 대조군의 동물들로부터 8주 후 혈액을 채취하여 GPT(glutamate-pyruvate transferase) 및 BUN(Blood Urea Nitrogen)의 혈액 내 농도를 Select E(Vital Scientific NV, Netherland) 기기를 이용하여 측정하였다. 그 결과, 간독성과 관계있는 것으로 알려진 GPT와 신장독성과 관계있는 것으로 알려진 BUN의 경우, 대조군과 비교하여 실험군은 별다른 차이를 보이지 않았다. 또한, 각 동물로부터 간과 신장을 절취하여 통상적인 조직절편 제작과정을 거쳐 광학현미경으로 조직학적 관찰을 시행하였으며 특이한 이상이 관찰되지 않았다. To examine the effects of C57BL / 6J mice on the organs (tissues) of the animals, blood samples were collected from the experimental group administered with the
<< 제제예Formulation example 1. 약학적 제제> 1. Pharmaceutical preparations>
제제예Formulation example 1-1. 1-1. 산제의Sanje 제조 Produce
본 발명의 화합물 1 또는 3을 2g, 유당 1g을 혼합하고 기밀포에 충진하여 산제를 제조하였다.2 g of the
제제예Formulation example 1-2. 정제의 제조 1-2. Manufacture of tablets
본 발명의 화합물 1 또는 3을 100㎎, 미결정셀룰로오스 100㎎, 유당수화물 60㎎, 저치환도히드록시프로필셀룰로오스 20mg 및 스테아르산마그네슘 2㎎을 혼합한 후 통상의 정제의 제조방법에 따라서 타정하여 정제를 제조하였다.100 mg of
제제예Formulation example 1-3. 캡슐제의 제조 1-3. Preparation of capsules
본 발명의 화합물 1 또는 3을 100㎎, 미결정셀룰로오스 100㎎, 유당수화물 60㎎, 저치환도히드록시프로필셀룰로오스 20mg 및 스테아르산마그네슘 2㎎을 혼합한 후 통상의 캡슐제 제조방법에 따라 상기의 성분을 혼합하고 젤라틴 캡슐에 충전하여 캡슐제를 제조하였다.100 mg of
제제예Formulation example 1-4. 주사제의 제조 1-4. Injection preparation
본 발명의 화합물 1 또는 3을 10㎎, 주사용 멸균 증류수 적량 및 pH 조절제 적량을 혼합한 후 통상의 주사제의 제조방법에 따라 1 앰플당(2㎖) 상기의 성분 함량으로 제조하였다.10 mg of the
<< 제제예Formulation example 2. 식품 제조> 2. Food Manufacturing>
제제예Formulation example 2-1. 조리용 양념의 제조 2-1. Manufacture of cooking seasonings
본 발명의 화합물 1 또는 3을 조리용 양념에 1 중량%로 첨가하여 건강 증진용 조리용 양념을 제조하였다.
제제예Formulation example 2-2. 밀가루 식품의 제조 2-2. Manufacture of flour food products
본 발명의 화합물 1 또는 3을 밀가루에 0.1 중량%로 첨가하고, 이 혼합물을 이용하여 빵, 케이크, 쿠키, 크래커 및 면류를 제조하여 건강 증진용 식품을 제조하였다.The
제제예Formulation example 2-3. 2-3. 스프soup 및 육즙(gravies)의 제조 And gravies
본 발명의 화합물 1 또는 3을 스프 및 육즙에 0.1 중량%로 첨가하여 건강 증진용 수프 및 육즙을 제조하였다.The health promotion soup and the juice were prepared by adding the
제제예Formulation example 2-4. 유제품(dairy products)의 제조 2-4. Manufacture of dairy products
본 발명의 화합물 1 또는 3을 우유에 0.1 중량%로 첨가하고, 상기 우유를 이용하여 버터 및 아이스크림과 같은 다양한 유제품을 제조하였다.
제제예Formulation example 2-5. 야채주스 제조 2-5. Vegetable juice manufacturing
0.5g의 본 발명의 화합물 1 또는 3을 토마토주스 또는 당근주스 1,000㎖에 가하여 건강 증진용 야채주스를 제조하였다. 0.5 g of the compound of the
제제예Formulation example 2-6. 과일주스 제조 2-6. Manufacture of fruit juice
0.1g의 본 발명의 화합물 1 또는 3을 사과주스 또는 포도주스 1,000㎖에 가하여 건강 증진용 과일주스를 제조하였다.0.1 g of the compound of the
Claims (6)
[화학식 1]
[Chemical Formula 1]
상기 조성물은 약제학적으로 허용되는 담체, 부형제 또는 희석제를 추가하여 약제학적 투여형으로 제형화되는 것을 특징으로 하는 알레르기 질환, 염증성 장질환, 전신성 홍반성낭창, 사구체신염, 피부 염증 질환, 유육종증, 망막염, 위염, 간염, 장염, 관절염, 편도선염, 인후염, 기관지염, 폐렴, 췌장염, 패혈증 및 신장염으로 이루어진 군에서 선택되는 염증성 질환의 예방 또는 치료용 약학 조성물.The method according to claim 1,
Wherein the composition is formulated into a pharmaceutical dosage form by addition of a pharmaceutically acceptable carrier, excipient or diluent, wherein the composition is formulated into a pharmaceutical dosage form, wherein the composition is formulated into a pharmaceutical dosage form comprising a pharmaceutically acceptable carrier, excipient or diluent. , Inflammatory diseases selected from the group consisting of gastritis, hepatitis, enteritis, arthritis, tonsillitis, sore throat, bronchitis, pneumonia, pancreatitis, sepsis and nephritis.
[화학식 1]
[Chemical Formula 1]
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