KR20090047851A - Treatment for autoimmune disease comprising artemisia extract - Google Patents
Treatment for autoimmune disease comprising artemisia extract Download PDFInfo
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- KR20090047851A KR20090047851A KR1020070113914A KR20070113914A KR20090047851A KR 20090047851 A KR20090047851 A KR 20090047851A KR 1020070113914 A KR1020070113914 A KR 1020070113914A KR 20070113914 A KR20070113914 A KR 20070113914A KR 20090047851 A KR20090047851 A KR 20090047851A
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- South Korea
- Prior art keywords
- cells
- extract
- mugwort extract
- autoimmune diseases
- autoimmune disease
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- Medicines Containing Plant Substances (AREA)
Abstract
본 발명은 쑥추출물을 유효성분으로 함유하는 자가면역질환 치료제에 관한 것으로, 상기 쑥추출물은 Th17 세포 분화 및 유지에 중추적인 역할을 하는 사이토카인인 p40 및 IL-17의 분비를 효과적으로 억제할 뿐 아니라, 루프스 동물모델을 포함한 다수의 자가면역질환 동물모델에서도 효과적인 치료효과를 나타내기 때문에 T세포의 비정상적인 활성으로 인해 발생하는 류마티스 관절염, 뇌척수염 및 전신 홍반성 낭창과 같은 자가면역질환의 치료제로 매우 유용하게 사용될 수 있다.The present invention relates to a therapeutic agent for autoimmune diseases containing mugwort extract as an active ingredient, the mugwort extract effectively inhibits the secretion of cytokines p40 and IL-17, which play a pivotal role in the differentiation and maintenance of Th17 cells. It is also useful as a therapeutic agent for autoimmune diseases such as rheumatoid arthritis, encephalomyelitis, and systemic lupus erythematosus caused by abnormal T-cell activity. Can be used.
쑥추출물, 자가면역질환, 류마티스 관절염, 뇌척수염, 전신 홍반성 낭창 Mugwort Extract, Autoimmune Disease, Rheumatoid Arthritis, Encephalomyelitis, Systemic Lupus Erythematosus
Description
본 발명은 쑥추출물을 유효성분으로 함유하는 자가면역질환 치료제, 즉 T세포의 비정상적인 활성으로 인해 발생하는 류마티스 관절염, 뇌척수염 및 전신 홍반성 낭창과 같은 자가면역질환 치료제에 관한 것이다.The present invention relates to a therapeutic agent for autoimmune diseases containing mugwort extract as an active ingredient, that is, to treat autoimmune diseases such as rheumatoid arthritis, encephalomyelitis and systemic lupus erythematosus caused by abnormal activity of T cells.
다양한 면역 질환 중에 자가면역질환은 현재까지 정확한 발병 원인이 밝혀지지 않았기 때문에 적절한 치료법이 없는 실정이다. 류마티스 관절염의 환자는 전체 인구의 1% 이상이 발병하는 것으로 알려져 있고, 주로 관절염 치료제와 소염 진통제, 스테로이드 등의 약물치료가 주로 사용되고 있다. Among various immune diseases, autoimmune diseases have not been found to be the proper cause because the exact cause of the disease to date. Patients with rheumatoid arthritis are known to cause more than 1% of the total population, mainly used for the treatment of arthritis, anti-inflammatory painkillers, steroids and the like.
생물학적 제제로써는 종양 괴사인자 알파(tumour necrosis factor-alpha: TNF-alpha) 저해제가 시장을 늘려가고 있으며, 수지상 세포를 이용한 치료가 시도되고 있으나 높은 의료비용이 부담으로 작용한다. As biological agents, tumor necrosis factor-alpha (TNF-alpha) inhibitors are increasing in the market, and treatment with dendritic cells is being tried, but high medical costs are burdensome.
전신 홍반성 낭창(SLE)은 병적인 자가 항체와 면역복합체에 의하여 조직 및 세포가 손상을 받는 원인 불명의 염증성 자가면역질환으로, 다른 류마티스 질환과 비슷하게 여자가 남자보다 10배 정도 많이 발생하며, 전 연령에서 발생이 가능하나 주로 가임기 연령 여성에서 많이 발생한다. Systemic lupus erythematosus (SLE) is an inflammatory autoimmune disease of unknown origin, in which tissues and cells are damaged by pathological autoantibodies and immunocomplexes.Similar to other rheumatic diseases, women develop about 10 times more than men. It can occur in age, but is most common in women of childbearing age.
흑인과 동양인이 백인보다 유병율이 높게 나타난다. SLE 환자를 위한 치료는 스테로이드 계열의 약물, 비스테로이드성 항염증제, 항말라리아제 및 면역억제제등을 사용하여 증상을 최소화하여 염증 반응을 줄이고 정상적인 신체기능을 유지할 수 있도록 하는 것이다. The prevalence of blacks and Asians is higher than that of whites. Treatment for SLE patients uses steroid-based drugs, nonsteroidal anti-inflammatory drugs, antimalarial agents and immunosuppressants to minimize symptoms and reduce inflammatory responses and maintain normal body function.
그러나 장기간 치료 시에 백내장, 골다공증, 두통, 혈압 증가 및 면역력 저하등과 같은 심각한 부작용을 야기한다. 그러므로 부작용을 최소화한 효과적인 자가면역치료제의 개발이 절실히 필요한 실정이다.However, long-term treatment causes serious side effects such as cataracts, osteoporosis, headaches, increased blood pressure and decreased immunity. Therefore, the development of effective autoimmune therapeutics with minimal side effects is urgently needed.
인체의 흉선에서 생성된 T 세포는 일련의 분화 과정을 거치면서 고유의 특성을 지닌 T 세포로 분화하게 된다. 분화를 완료한 T 세포는 그 기능에 따라 크게 1형 보조 세포(Th1)와 2형 보조 세포(Th2)로 구분된다. T cells produced in the human thymus go through a series of differentiation processes to differentiate into T cells with unique characteristics. T cells that have completed differentiation are classified into
Th1 세포의 주된 기능은 세포 매개성 면역에 관여를 하며 Th2 세포는 체액성 면역에 관여를 하고 있다. 면역계에서 이 두 세포 집단은 서로 과 활성화되지 않도록 서로 견제를 통한 면역계의 균형을 유지하고 있다. The main function of Th1 cells is involved in cell mediated immunity and Th2 cells are involved in humoral immunity. In the immune system, these two cell populations balance the immune system with each other to prevent over-activation.
그러므로 면역 질환의 대부분은 두 면역 세포간의 불균형에 기인하는 것으로 볼 수 있다. 예를 들어 Th1 세포의 활성이 비정상적으로 증가하는 경우 자가면역질환이 우세하게 나타날 수 있으며, Th2 세포의 활성이 비정상적으로 증가하는 경우 과민반응에 의한 면역질환이 발생하는 것으로 알려져 있다. Therefore, most of the immune diseases can be attributed to the imbalance between two immune cells. For example, autoimmune diseases may prevail when the activity of Th1 cells is abnormally increased, and immune diseases caused by hypersensitivity reactions are known to occur when the activity of Th2 cells is abnormally increased.
Th1 세포의 분화에 대한 최근 일련의 연구 결과, Th1 세포의 활성을 조절 할 수 있는 새로운 그룹인 조절 T세포(Treg)의 존재가 알려지면서 이를 이용한 면역질 환의 치료가 효과를 거두고 있다. Recent studies on the differentiation of Th1 cells have revealed the existence of a new group of regulatory T cells (Tregs) that can control Th1 cell activity.
Treg 세포는 비정상적으로 활성화된 면역세포의 기능을 억제하여 염증 반응을 제어하는 것으로 알려져 있다. 그러므로 Treg 세포의 활성을 증가시켜 면역질환을 치료하는 실험들이 많이 보고되고 있다. Treg cells are known to control the inflammatory response by inhibiting the function of abnormally activated immune cells. Therefore, many experiments have been reported to treat immune diseases by increasing the activity of Treg cells.
실제 본 발명자는 천연물로부터 탄닌 계열의 체불락산(chebulagic acid)을 분리하였으며, 이 성분이 Treg 세포의 분화를 증가시킴으로써 콜라젠에 의해 발생하는 류마티스 관절염에서 우수한 치료 효과를 보임을 밝혀내었다. Indeed, the present inventors have isolated tannin-based chebulagic acid from natural products, and found that this component shows an excellent therapeutic effect in rheumatoid arthritis caused by collagen by increasing the differentiation of Treg cells.
새로운 Treg 세포 그룹 외에 분화 과정에서 만들어지는 또 다른 그룹인 Th17 세포는 미분화 T세포의 분화 과정에서 Treg 세포의 분화와 유사한 과정을 거치며 형성되는 것으로 알려져 있다. In addition to the new Treg cell group, Th17 cells, another group produced during the differentiation process, are known to be formed through a process similar to the differentiation of Treg cells during the differentiation of undifferentiated T cells.
즉 Treg 세포와 Th17 세포의 분화는 공통적으로 TGF-β의 존재 하에서 이루어지지만 Treg 세포의 경우 IL-6을 필요로 하지 않는다. 그러나 Th17 세포의 경우 TGF-β와 함께 IL-6이 존재하는 상황에서 분화를 한다. 분화된 Th17 세포는 IL-17을 분비하는 것을 특징으로 한다. In other words, differentiation of Treg cells and Th17 cells occurs in the presence of TGF-β in common, but Treg cells do not require IL-6. However, Th17 cells differentiate in the presence of IL-6 with TGF-β. Differentiated Th17 cells are characterized by secreting IL-17.
그러므로 Th17 세포는 Treg 세포와는 달리 면역질환에서 보이는 염증반응의 최전방에서 관여를 하여 염증 반응의 신호를 최대화시켜 질병의 진행을 가속화시키는 것이 밝혀지고 있다. Therefore, Th17 cells, unlike Treg cells, are involved in the forefront of the inflammatory response seen in immune diseases, maximizing the signal of the inflammatory response and accelerating disease progression.
따라서, 자가면역질환 중 Treg 세포에 의해 제어되지 않는 자가면역질환에 있어서 Th17 세포 활성의 억제를 표적으로 한 자가면역질환의 치료제 개발이 크게 부각되고 있다.Therefore, the development of a therapeutic agent for autoimmune diseases, which targets the inhibition of Th17 cell activity in autoimmune diseases not controlled by Treg cells among autoimmune diseases, has been highlighted.
현재 사용되고 있는 면역질환치료제는 전통적으로 사용되어 온 사이클로스포린이나 FK506과 같이 칼슘 및 칼모듈린 의존성 단백인산화 효소인 칼시뉴린(calcineurin)에 결합하여 그 작용을 방해함으로써 T세포에서의 신호변환 경로를 차단하는 면역 억제제가 가장 많이 사용되고 있다. Currently used immunotherapeutic agents block the signal transduction pathways in T cells by binding to and interfering with the action of calcineurin, a calcium and calmodulin-dependent protein kinase, such as cyclosporine and FK506, which have been traditionally used. Immune inhibitors are the most used.
그러나 이러한 면역억제제들은 신독성, 감염, 임파종, 당뇨병, 진전(tremor), 두통, 설사, 고혈압, 오심, 신기능 장애 등의 부작용이 따르게 된다. 항체를 이용한 면역 제어로써 IL-2 수용체와 OKT 3에 대한 항체를 사용하여 T세포가 활성화되는 것을 억제하는 방법이 사용된다. However, these immunosuppressive agents are accompanied by side effects such as renal toxicity, infection, lymphoma, diabetes, tremor, headache, diarrhea, high blood pressure, nausea and renal dysfunction. As an immune control using an antibody, a method of inhibiting T cell activation using an antibody against the IL-2 receptor and
T세포의 활성화를 억제하는 방법 이외에 면역 세포로부터 분비되는 사이토카인의 양을 조절하는 생물학 제제 역시 중요한 치료법으로 인식되고 있다. 실제 자가면역질환의 치료에 있어서 체액성 면역력을 증가시키는 방법이 시도되고 있다. In addition to inhibiting T cell activation, biological agents that regulate the amount of cytokines secreted from immune cells are also recognized as important therapies. In practice, a method of increasing humoral immunity has been attempted in the treatment of autoimmune diseases.
또한, 면역 세포로부터 분비되는 사이토카인을 표적으로 한 단일클론 항체가 개발 중에 있다. 실제 종양 괴사 유전자(TNF-α)에 대한 단일클론 항체는 류마티스 관절염의 치료에 사용되고 있다. In addition, monoclonal antibodies targeting cytokines secreted from immune cells are under development. Indeed, monoclonal antibodies against tumor necrosis gene (TNF-α) have been used for the treatment of rheumatoid arthritis.
또한, IL-12/23의 구조체인 p40, IL-15 및 IL-17에 대한 단일클론 항체는 FDA의 승인을 받았거나 임상 실험 단계를 거치고 있는 중이다. 그러나 이러한 단일클론 항체는 상대적으로 고가인 관계로 보다 저렴하고 효과적인 면역 조절제의 필요성을 제시하고 있다. In addition, monoclonal antibodies against p40, IL-15 and IL-17, the structures of IL-12 / 23, are either approved by the FDA or are undergoing clinical trials. However, these monoclonal antibodies are relatively expensive, suggesting the need for cheaper and more effective immunomodulators.
현재 임상 단계인 p40이나 IL-17 단일클론 항체는 실제 Th17 세포의 분화와 유지에 가장 핵심적인 사이토카인으로 알려져 있기 때문에 이 두 사이토카인을 조 절하는 활성을 지닌 물질은 자가면역질환의 치료에 매우 효과적으로 응용될 수 있다는 것을 시사하고 있다.Since p40 and IL-17 monoclonal antibodies, which are currently in clinical stages, are known to be the most important cytokines for the differentiation and maintenance of Th17 cells, substances with activity controlling these two cytokines are very useful for the treatment of autoimmune diseases. It can be applied effectively.
한편, 쑥(Artemisia mongolica, A. asiatica, A. princeps, A. argyi 등)은 국화과(Compositae)에 속하는 다년생 초본으로서 여러나라에서 자생하고 있으며, 독특한 향기와 맛을 갖고 있다. Mugwort ( Artemisia mongolica , A. asiatica , A. princeps , A. argyi, etc.) is a perennial herb belonging to Compositae, which grows in many countries and has a unique aroma and taste.
우리나라에서는 말린 잎을 애엽이라 하며, 자궁을 온난케 하고 자궁출혈, 임신중의 출혈 등에 효과가 있다고 알려져 왔으며, 강장보혈, 부인병, 설사치료제로 쓰여 왔다(동의보감). In Korea, dried leaves are called lobars, which have been known to warm the uterus, uterine bleeding and bleeding during pregnancy, and have been used to treat tonic blood, gynecological diseases, and diarrhea.
쑥 속의 유효성분으로는 이소쿠마린(isocoumarin), 쿠마린(coumarin), 다이터펜락톤(diterpenlactone), 플라보노이드(flavonoid), 펠란드렌(phellandrene), 큐프롤(cuprol), 카디넨(cardinene) 등이 밝혀져 있다(대한약전외 생약규격집; Plants Med . 60: 437, 1994; J, Nat . Prod . 44(5): 586-7, 1981; HerbaHungarica, Tom. 24 No.2-3, 1985). The active ingredients in mugwort include isocoumarin, coumarin, dieterpenlactone, flavonoids, phellandrene, cuprol, and cardinene. (National Herb Medicine Standards; Plants Med . 60: 437, 1994; J, Nat . Prod . 44 (5): 586-7, 1981; Herba Hungarica, Tom. 24 No. 2-3, 1985).
쑥의 약리작용에 대해 살펴보면, 쑥의 물추출물은 혈액 응고시간을 현저히 연장시키며(약학회지 제28권 제2호 69-77, 1984), 쑥으로부터 추출한 플라본(flavone)은 항암효과가 있고(Tetrahedron 25(8): 1603-15, 1969; Chem . Pharm . Bull. 32(2): 723-727, 1984), 항진균활성이 있으며(J. of Chemical Ecology, 19(11), 1993), 항보체작용을 하여 숙주의 방어체제를 도와서 알러지나 염증에 효과가 있고(Chem . Pharm . Bull . 33(5): 2028-2034, 1985), 혈압강하 작용과 진정작용(Indian J. Med . Res . 60, 1972)을 한다고 보고된 바 있다. Referring to the pharmacological action of wormwood, mugwort water extract sikimyeo significantly prolong the clotting time (about Journal of claim 28 No. 2 69-77, 1984), flavones (flavone) extracted from Artemisia may have anticancer activity (Tetrahedron 25 (8): 1603-15, 1969; Chem . Pharm . Bull. 32 (2): 723-727, 1984) and have antifungal activity ( J. of Chemical Ecology , 19 (11), 1993), anti-complementation to help host defenses and to be effective in allergies and inflammation ( Chem . Pharm . Bull . 33 (5): 2028-2034, 1985), lowering blood pressure And sedation ( Indian J. Med . Res . 60, 1972).
이외의 성분으로 유파틸린(Eupatilin)이 규명되었으며, 이것의 항알러지 효과(일본 공개특허공보 소59-155314)에 대해서도 보고되어 있다. Eupatilin was identified as another component, and its anti-allergic effect (Japanese Unexamined Patent Publication No. 59-155314) has also been reported.
또한 유파틸린과 자세오시딘을 주요 성분으로 하는 위장질환 치료제가 출원되어 있으나 이러한 위장 질환에 대한 약리 효과는 위장을 구성하는 세포로부터 프로스타글란딘의 유리를 억제하는 경로가 주요한 질환 표적으로 인식되고 있으며 면역 조절 활성, 특히 Th17 세포의 분화 억제 효과에 관한 검토는 전혀 없다.In addition, there have been applied for treating gastrointestinal diseases, which are mainly composed of eupatillin and postural oscidine, but the pharmacological effect on gastrointestinal diseases is recognized as a major disease target that inhibits the release of prostaglandins from the cells of the stomach. There is no review of the activity, in particular the effect of inhibiting the differentiation of Th17 cells.
본 발명의 목적은 자가면역질환과 직접 관련된 두 가지 사이토카인인 p40과 IL-17의 분비를 효과적으로 억제하며, 자가면역질환 실험동물모델에서도 치료효과를 나타내는 자가면역질환 치료제 및 자가면역질환 개선용 건강식품을 개발하는 데에 있다.An object of the present invention is to effectively inhibit the secretion of two cytokines, p40 and IL-17, which are directly related to autoimmune diseases, and to improve autoimmune diseases and improve the health of autoimmune diseases. It is in developing food.
상기 목적을 달성하기 위하여, 본 발명은 쑥추출물을 유효성분으로 함유하는 자가면역질환 치료제을 제공한다.In order to achieve the above object, the present invention provides a therapeutic agent for autoimmune diseases containing mugwort extract as an active ingredient.
쑥추출물은 쑥잎을 C1 내지 C4의 알코올 또는 이의 수용액으로 추출하며, 상기 추출은 냉침, 환류 또는 초음파 등의 방법에 의할 수 있고, 상기 쑥추출물은 유파틸린 및 자세오시딘을 함유한다.Mugwort extract extracts mugwort leaves with alcohol of C1 to C4 or an aqueous solution thereof, and the extract may be by cold, reflux, or ultrasonic method, and the mugwort extract contains eupatillin and postiodine.
상기 자가면역질환은 류마티스 관절염, 뇌척수염 및 전신 홍반성 낭창으로 이루어진 군에서 선택된 어느 하나의 질환인 것이 바람직하다.The autoimmune disease is preferably any one selected from the group consisting of rheumatoid arthritis, encephalomyelitis and systemic lupus erythematosus.
또한, 본 발명은 쑥추출물을 유효성분으로 함유하는 자가면역질환 개선용 건강식품을 제공한다.In addition, the present invention provides a health food for improving autoimmune diseases containing wormwood extract as an active ingredient.
이하, 본 발명을 보다 상세하게 설명한다.Hereinafter, the present invention will be described in more detail.
본 발명자들은 쑥추출물이 T 세포가 TGF-β와 IL-6의 자극에 의해 분화된 Th17 세포가 분비하는 IL-17를 감소시키며, 또한 Th17 세포의 유지를 위해 필요한 항원제시세포(antigen-presenting cell)가 분비하는 IL23p40의 분비를 억제하는 활성을 갖는 것을 확인하였고, 또한 류마티스 관절염과 뇌척수염의 실험동물모델에 있어서 질병의 발병을 늦춤과 동시에 치료 효과를 보이는 것을 확인하였고, 루프스 모델에서 혈중 IL-17의 농도를 낮추는 것을 확인하였으며, 이에 본 발명을 완성하게 되었다.The present inventors have found that mugwort extract reduces IL-17 secreted by Th17 cells differentiated by TGF-β and IL-6 stimulation, and is also required for the maintenance of Th17 cells. ) Inhibited the secretion of IL23p40 secretion, and in the experimental animal model of rheumatoid arthritis and encephalomyelitis, it was confirmed that it showed a therapeutic effect at the same time as the disease onset, and blood IL-17 in the Lupus model. It was confirmed to lower the concentration of, thereby completing the present invention.
본 발명의 쑥추출물은 전체 자가면역질환 치료제 100 중량부에 대하여 0.5-50 중량부로 함유되는 것이 바람직하다. 만약, 쑥추출물이 상기 범위를 벗어나 소량으로 함유되면 약효 발생의 저하가 야기될 수 있는 반면, 다량으로 함유되면 혈액 응고 억제와 같은 부작용이 야기될 수 있다.Mugwort extract of the present invention is preferably contained in 0.5-50 parts by weight based on 100 parts by weight of the total autoimmune disease treatment. If the wormwood extract is contained in a small amount outside the above range may cause a decrease in the efficacy of the drug, while containing a large amount may cause side effects such as inhibiting blood coagulation.
또한, 본 발명에 따른 자가면역질환 치료제는 약학조성물의 제조에 통상적으로 사용하는 적절한 담체, 부형제 또는 희석제를 더 포함할 수 있다. In addition, the autoimmune disease therapeutic agent according to the present invention may further include a suitable carrier, excipient or diluent commonly used in the manufacture of a pharmaceutical composition.
본 발명에서 사용가능한 담체, 부형제 또는 희석제로는, 락토즈, 덱스트로즈, 수크로스, 솔비톨, 만니톨, 자일리톨, 에리스리톨, 말티톨, 전분, 아카시아 고무, 알지네이트, 젤라틴, 칼슘 포스페이트, 칼슘 실리케이트, 셀룰로즈, 메틸 셀룰로즈, 미정질 셀룰로스, 폴리비닐 피롤리돈, 물, 메틸히드록시벤조에이트, 프로필히드록시벤조에이트, 탈크, 마그네슘 스테아레이트 또는 광물유 등을 들 수 있다.Carriers, excipients or diluents usable in the present invention include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, Methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, mineral oil, and the like.
본 발명에 따른 자가면역질환 치료제는, 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.The therapeutic agent for autoimmune diseases according to the present invention may be formulated in the form of powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols and the like, external preparations, suppositories, and sterile injectable solutions, respectively, according to a conventional method. Can be used.
제제화할 경우에는 보통 사용하는 충진제, 증량제, 결합제, 습윤제, 붕해제, 계면활성제 등의 희석제 또는 부형제를 사용하여 조제된다. 경구투여를 위한 고형제제에는 정제, 환제, 산제, 과립제, 캡슐제 등이 포함되며, 이러한 고형제제는 상기 화합물은 적어도 하나 이상의 부형제, 예를 들면, 전분, 칼슘카보네이트(calcium carbonate), 수크로스(sucrose) 또는 락토오스(lactose), 젤라틴 등을 섞어 조제한다. When formulated, diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrating agents, and surfactants are usually used. Solid preparations for oral administration include tablets, pills, powders, granules, capsules, and the like, and the solid preparations may include at least one excipient, for example, starch, calcium carbonate, sucrose ( Prepare by mixing sucrose or lactose, gelatin, etc.
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. In addition to simple excipients, lubricants such as magnesium stearate and talc are also used. Oral liquid preparations include suspensions, solvents, emulsions, and syrups, and may include various excipients, such as wetting agents, sweeteners, fragrances, and preservatives, in addition to commonly used simple diluents such as water and liquid paraffin. .
비경구 투여를 위한 제제에는 멸균된 수용액, 비수성용제, 현탁제, 유제, 동결건조 제제, 좌제가 포함된다. 비수성용제, 현탁제로는 프로필렌글리콜(propylene glycol), 폴리에틸렌 글리콜, 올리브 오일과 같은 식물성 기름, 에틸올레이트와 같은 주사 가능한 에스테르 등이 사용될 수 있다. 좌제의 기제로는 위텝솔(witepsol), 마크로골, 트윈(tween) 61, 카카오지, 라우린지, 글리세로제라틴 등이 사용될 수 있다.Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations, suppositories. As the non-aqueous solvent and suspending agent, propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate and the like can be used. As the base of the suppository, witepsol, macrogol, tween 61, cacao butter, laurin butter, glycerogelatin and the like can be used.
본 발명에서 쑥추출물의 사용량은 환자의 나이, 성별, 체중에 따라 달라질 수 있으나, 10 내지 1000 mg/㎏의 양을 일일 1회 내지 수회 투여할 수 있다. In the present invention, the amount of mugwort extract used may vary depending on the age, sex, and weight of the patient, but may be administered once to several times daily in an amount of 10 to 1000 mg / kg.
또한, 쑥추출물의 투여량은 투여경로, 질병의 정도, 성별, 체중, 나이 등에 따라서 증감될 수 있다. 따라서, 상기 투여량은 어떠한 면으로든 본 발명의 범위를 한정하는 것은 아니다.In addition, the dosage of the mugwort extract may be increased or decreased depending on the route of administration, degree of disease, sex, weight, age, and the like. Therefore, the above dosage does not limit the scope of the present invention in any aspect.
상기 자가면역질환 치료제는 쥐, 생쥐, 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(intracerebroventricular)주사에 의해 투여될 수 있다.The autoimmune disease therapeutic agent may be administered to various mammals such as rats, mice, livestock, humans, and the like. All modes of administration can be expected, for example, by oral, rectal or intravenous, intramuscular, subcutaneous, intrauterine dural or intracerebroventricular injection.
상기 쑥추출물은 천연약재로서 안전한 물질이며, 특히 랫트에서 아주 많은 양을 경구투여하여도 급성독성을 전혀 나타내지 않는 것으로 알려져 있다.The mugwort extract is a safe substance as a natural medicine, and is known to show no acute toxicity, even if administered orally in large amounts, especially in rats.
또한, 본 발명은 쑥추출물을 유효성분으로 함유하는 자가면역질환 개선용 건강식품을 제공한다.In addition, the present invention provides a health food for improving autoimmune diseases containing wormwood extract as an active ingredient.
상기 건강식품은 쑥추출물 이외에 다른 식품 또는 식품 첨가물과 함께 사용되고, 통상적인 방법에 따라 적절하게 사용될 수 있다. 유효성분의 혼합양은 그의 사용 목적 예를들어 예방, 건강 또는 치료적 처치에 따라 적합하게 결정될 수 있다. The health food is used in conjunction with other food or food additives in addition to mugwort extract, it may be appropriately used in accordance with conventional methods. The mixed amount of the active ingredient may be appropriately determined depending on the purpose of use thereof, for example, prophylactic, health or therapeutic treatment.
상기 건강식품에 함유된 쑥추출물의 유효용량은 상기 치료제의 유효용량에 준해서 사용할 수 있으나, 건강 및 위생을 목적으로 하거나 또는 건강 조절을 목적으로 하는 장기간의 섭취의 경우에는 상기 범위 이하일 수 있으며, 유효성분은 안전성 면에서 아무런 문제가 없기 때문에 상기 범위 이상의 양으로도 사용될 수 있음은 확실하다.The effective dose of mugwort extract contained in the health food may be used in accordance with the effective dose of the therapeutic agent, but may be less than the above range in the case of long-term intake for health and hygiene purposes or health control purposes, It is evident that the active ingredient can be used in an amount above the above range because there is no problem in terms of safety.
상기 건강식품의 종류에는 특별한 제한이 없고, 예로는 육류, 소세지, 빵, 쵸코렛, 캔디류, 스넥류, 과자류, 피자, 라면, 기타 면류, 껌류, 아이스크림류를 포함한 낙농제품, 각종 스프, 음료수, 차, 드링크제, 알콜 음료 및 비타민 복합제 등을 들 수 있다.There is no particular limitation on the kind of the health food, for example, meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, gums, dairy products including ice cream, various soups, drinks, tea, Drinks, alcoholic drinks, vitamin complexes, etc. are mentioned.
또한, 본 발명의 쑥추출물은 기존의 한방에 첨가하여 복합처방함으로써 기존 한방의 약효를 월등히 증진시킬 수 있다.In addition, the mugwort extract of the present invention can further enhance the efficacy of the conventional herbal medicine by adding to the existing herbal complex prescription.
본 발명에 따른 쑥추출물은 p40 및 IL-17의 분비를 효과적으로 억제할 뿐만 아니라, 자가면역질환 동물실험모델에서도 탁월한 치료효과를 나타냄으로써 류마티스 관절염, 뇌척수염 및 전신 홍반성 낭창과 같은 자가면역질환의 치료제로써 유용하게 사용할 수 있다.Mugwort extract according to the present invention not only effectively inhibits the secretion of p40 and IL-17, but also shows an excellent therapeutic effect in animal models of autoimmune diseases, thereby treating autoimmune diseases such as rheumatoid arthritis, encephalomyelitis and systemic lupus erythematosus. It can be usefully used.
본 발명의 이해를 돕기 위하여 바람직한 실시예를 하기에 제시한다. 그러나 이러한 실시예는 본 발명을 보다 쉽게 이해하기 위하여 제공되는 것일 뿐 본 발명이 하기의 실시예에 한정되는 것은 아니다.Preferred examples are provided below to aid in the understanding of the present invention. However, these examples are only provided to more easily understand the present invention, the present invention is not limited to the following examples.
<실시예 1> 쑥추출물의 제조Example 1 Preparation of Mugwort Extract
세절한 쑥잎 100g을 100% 에탄올 1L로 상온에서 24시간 1회 추출하였고 추출여액을 감압농축한 뒤 동결건조하여 고형분 5.4g을 얻었다. 고형분은 50% 에탄올에 녹여 헥산으로 탈지한 층과 수용성 층으로 구분하였다. 100 g of fine mugwort leaves were extracted once with 24 L of 100% ethanol at room temperature for 24 hours. The filtrate was concentrated under reduced pressure and lyophilized to obtain 5.4 g of solid. Solid content was divided into a hexane-degreased layer and a water-soluble layer dissolved in 50% ethanol.
수용성 층은 클로로포름으로 분획하였으며 분리된 수용성 층은 에틸아세테이트 층과 수용성 층으로 분획하였다. 최종적으로 분획된 각층의 건조 중량은 각각 2.5g(헥산층), 1.8g(클로로포름층), 0.6g(에틸아세테이트층) 및 0.3g(수층)이었다. The water-soluble layer was fractionated with chloroform, and the separated water-soluble layer was partitioned into an ethyl acetate layer and a water-soluble layer. The dry weights of the finally fractionated layers were 2.5 g (hexane layer), 1.8 g (chloroform layer), 0.6 g (ethyl acetate layer) and 0.3 g (aqueous layer), respectively.
각 분획층의 활성 검사에서는 에틸아세테이트 층에서 가장 높은 활성을 보임 을 확인하였고, 이하의 실험예에 기재된 in vitro 및 in vivo 실험은 상기 에틸아세테이트 층으로 수행하였다. It was confirmed that the activity test of each fraction layer showed the highest activity in the ethyl acetate layer, in vitro and in vivo experiments described in the following experimental example was performed with the ethyl acetate layer.
HPLC 분석을 통해 상기 고형분 중 유파틸린의 함량은 0.84% 및 자세오시딘의 함량은 0.41%였다. 주성분 분석의 HPLC 조건은 칼럼이 Inertsil ODS-II C 4.6mm ID X 150mm L; 이동상이 1% 초산암모늄, 0.5% 초산완충액:아세토니트릴(60:40) 혼액; 유속 1ml/min; 검출은 UV, 360nm; 및 주입량이 10㎕였다.The HPLC analysis showed that the content of eupatillin in the solids was 0.84% and that of zithrodine was 0.41%. HPLC conditions of Principal Component Analysis showed that the column had Inertsil ODS-II C 4.6 mm ID × 150 mm L; Mobile phase contains 1% ammonium acetate, 0.5% acetate buffer: acetonitrile (60:40) mixture;
<실험예 1> 사이토카인 분비능 검토Experimental Example 1 Review of Cytokine Secretion Capacity
1) 염증성 사이토카인 분비능 검토1) Inflammatory cytokine secretion review
마우스로부터 유래한 J774.1 세포(5×104/well)를 96 well plate에 분주하고 25㎍/㎖ 및 50㎍/㎖의 농도로 실시예 1에서 제조한 쑥추출물을 첨가하여 30분간 배양한 뒤, LPS(1㎍/㎖)로 18시간 동안 자극한 뒤 배양액에 존재하는 IL-1β 및 IL-6의 양을 조사하였다. J774.1 cells (5 × 10 4 / well) derived from mice were dispensed into 96 well plates and incubated for 30 minutes with the addition of the mugwort extract prepared in Example 1 at concentrations of 25 µg / ml and 50 µg / ml. After stimulation with LPS (1 μg / ml) for 18 hours, the amount of IL-1β and IL-6 present in the culture was investigated.
IL-1β 및 IL-6의 양은 Biosource(Carmarilo, CA)사의 ELISA 키트를 사용하여 제조자의 지시에 따라 측정하였고, 배양액에 존재하는 IL-1β 및 IL-6의 양은 표준곡선을 통해 정량화하였다.The amounts of IL-1β and IL-6 were measured according to the manufacturer's instructions using an ELISA kit of Biosource (Carmarilo, Calif.), And the amounts of IL-1β and IL-6 present in the culture were quantified through a standard curve.
그 결과, 쑥추출물 25㎍/㎖의 농도에서도 염증성 사이토카인인 IL-1β 및 IL-6이 50% 이상 억제하는 것을 확인하였다(도 1a 및 도 1b 참조). As a result, it was confirmed that inflammatory cytokines IL-1β and IL-6 were inhibited by 50% or more even at the concentration of the mugwort extract 25㎍ / ㎖ (see Fig. 1a and 1b).
또한, 전사 수준에서 두 유전자의 변화를 살펴보기 위해 RAW264.7 세포(2×105cell/well)를 12 well plate에 분주하고 50㎍/㎖의 농도로 실시예 1에서 제조한 쑥추출물을 첨가하여 30분간 배양한 뒤, LPS(1㎍/㎖)로 3시간 동안 자극한 뒤 RNA를 분리하여 역전사 반응을 통해 cDNA를 합성하였다. In addition, RAW264.7 cells (2 × 10 5 cell / well) were dispensed into 12 well plates and the mugwort extract prepared in Example 1 was added at a concentration of 50 μg / ml to examine the change of the two genes at the transcription level. After culturing for 30 minutes, and stimulated with LPS (1㎍ / ㎖) for 3 hours, RNA was isolated to synthesize cDNA through reverse transcription reaction.
합성된 cDNA를 주형으로 RT-PCR을 통해 IL-1β 및 IL-6의 유전자 양을 조사한 결과, 단백질의 결과와 같이 유전자의 양도 줄어 있음을 확인할 수 있었다(도 2 참조).As a result of investigating the gene amounts of IL-1β and IL-6 through RT-PCR using the synthesized cDNA as a template, it was confirmed that the amount of genes was reduced as well as the result of the protein (see FIG. 2).
2) IL-23p40 분비능 검토2) IL-23p40 Secretion Review
항원제시세포로부터 유리되는 IL-23은 Th0 세포를 자극하여 Th17 세포로 분화시키는 직접적인 역할을 수행하는 것으로 알려져 있는 바, 마우스로부터 유래한 J774.1 세포(5×104/well)를 96 well plate에 분주하고 25㎍/㎖ 및 50㎍/㎖의 농도로 실시예 1에서 제조한 쑥추출물을 첨가하여 30분간 배양한 뒤, LPS(1㎍/㎖)로 18시간 동안 자극한 뒤 배양액에 존재하는 p40의 양을 조사하였다. IL-23, released from antigen-presenting cells, is known to play a direct role in stimulating Th0 cells to differentiate into Th17 cells. 96 well plates of J774.1 cells (5 × 10 4 / well) derived from mice After culturing for 30 minutes by adding the mugwort extract prepared in Example 1 at concentrations of 25 µg / ml and 50 µg / ml, and stimulating with LPS (1 µg / ml) for 18 hours, The amount of p40 was investigated.
p40의 양은 eBioscience(San Diego, CA)사의 ELISA 키트를 사용하여 제조자의 지시에 따라 측정하였다. 배양액에 존재하는 p40의 양은 표준곡선을 통해 정량화하였다.The amount of p40 was measured using the ELISA kit of eBioscience (San Diego, Calif.) according to the manufacturer's instructions. The amount of p40 present in the culture was quantified through a standard curve.
그 결과, 다른 염증성 사이토카인과 마찬가지로 쑥추출물 25㎍/㎖의 농도에서도 50% 이상 억제하는 것을 확인하였으며 이는 T 세포의 분화 과정에서 쑥추출물이 Th17 세포로의 분화를 효과적으로 억제할 수 있다는 것을 시사한다(도 3 참조). As a result, it was confirmed that as in the other inflammatory cytokines, mugwort extract inhibited more than 50% even at the concentration of mugwort extract 25㎍ / ㎖, suggesting that the mugwort extract can effectively inhibit the differentiation into Th17 cells during the differentiation of T cells. (See Figure 3).
또한, 산지가 다른 두 종류의 약재(중국 하북, 중국 운남)의 활성을 비교한 결과 역시 활성의 차이를 보이지 않음으로써 안정적인 원료의 공급도 가능한 것으 로 나타났다.In addition, as a result of comparing the activity of two kinds of medicinal herbs (Hebei, Henan, China, Yunnan, China) with different origin, it also showed that it is possible to supply stable raw materials.
<실험예 2> 루프스 동물모델 평가Experimental Example 2 Evaluation of Lupus Animal Model
쑥추출물이 실제 체내에서도 안정적인 상태로 존재하며 Th17 세포의 분화를 억제하는지를 확인하기 위하여 루프스 동물모델인 NZBW 마우스를 이용하여 검증하였다. Mugwort extract was present in a stable state in the body and was verified using NZBW mice, a Lupus animal model, to confirm whether the inhibition of Th17 cell differentiation.
생후 30주령 전후의 NZBW 마우스는 단백뇨의 발생과 함께 혈중 IL-17의 농도가 크게 증가되어 있는 것을 확인하였다. IL-17의 농도가 증가된 NZBW 마우스에 실시예 1에서 제조한 쑥추출물을 50㎎/㎏ 및 100㎎/㎏의 농도로 11일간 경구 투여하였다. NZBW mice around 30 weeks of age were found to have a significant increase in serum IL-17 levels with the development of proteinuria. Mugwort extracts prepared in Example 1 were orally administered to NZBW mice with increased IL-17 concentrations at 50 mg / kg and 100 mg / kg for 11 days.
실험 전, 투여 6일째 및 11일째에 꼬리 미정맥을 통해 채혈하여 혈청을 분리하였다. 혈청내의 IL-17의 양은 p40의 양은 eBioscience(San Diego, CA)사의 ELISA 키트를 사용하여 제조자의 지시에 따라 측정하였다. Serum was isolated by bleeding through the tail vein on
실제 증가된 IL-17은 쑥추출물을 투여한 시점에서부터 감소하기 시작하여 6일 후에는 40% 가량 감소되는 것을 보였으며 11일째 투여한 경우 50% 이상 감소되어 있는 것을 확인할 수 있었다. In fact, the increased IL-17 began to decrease from the time of administration of mugwort extract, and after 6 days, it showed a decrease of about 40%.
이는 쑥추출물이 실제 체내에서 효과적으로 작용한다는 것을 확인해 주는 것으로 실체 면역계에서 생성된 Th17 세포의 수를 조절함으로써 루프스와 같은 자가 면역 질환에 효과적 치료제라는 것을 입증한다(도 4). This confirms that wormwood extract works effectively in the body, demonstrating that it is an effective treatment for autoimmune diseases such as Lupus by controlling the number of Th17 cells produced in the body's immune system (FIG. 4).
<실험예 3> EAE 동물모델 평가Experimental Example 3 Evaluation of EAE Animal Model
뇌척수염에 대한 보호 효과를 알아보기 위해 질환 모델인 SJL 마우스에 PLP139??151 펩타이드 80㎍과 40㎍의 미코박테리움 튜버큘로시스(Mycobacterium tuberculosis)가 현탁된 200㎕의 CFA(Complete Freund`s adjuvant)를 등 쪽에 피하 주사하였다. To investigate the protective effect against encephalomyelitis, 200 μl of Complete Freund`s adjuvant containing 80 μg of PLP 139 ?? 151 peptide and 40 μg of Mycobacterium tuberculosis was suspended in SJL mice . ) Was injected subcutaneously into the dorsal side.
이와 함께 백일해 독소(pertusis toxin) 100ng을 미정맥을 통해 주사하였다. 질환 발생의 판단은 Chen Y 등(J. Clin. Invest. 116: 1317-1326, 2006)의 방법에 준하여 측정하였다. In addition, 100 ng of pertusis toxin was injected through the vein. The incidence of disease was measured according to the method of Chen Y et al. ( J. Clin. Invest. 116: 1317-1326, 2006).
추출물의 투여는 EAE(experimental allergic/autoimmune encephalomyelitis) 유도 후 일주일이 경과한 뒤 실시예 1에서 제조한 쑥추출물은 7일째부터 각각 50, 100㎎/kg의 농도로 하루 1회씩 복강 투여하면서 질병의 발생을 관찰하였다.The administration of the extract was one week after the induction of experimental allergic / autoimmune encephalomyelitis (EAE), and the mugwort extract prepared in Example 1 was intraperitoneally administered once a day at a concentration of 50 and 100 mg / kg from day 7, respectively, to develop the disease. Was observed.
도 5에 도시된 바와 같이, 두 농도에서 각각 질병의 발생이 3일에서 5일 정도 늦어지는 것을 확인할 수 있었으며 EAE 질병 지수 역시 대조군에 비해 50㎎/kg 농도에서는 30%, 100㎎/kg 농도에서는 약 50% 가까이 감소하는 것이 확인되었다. As shown in FIG. 5, it was confirmed that the incidence of the disease was delayed by 3 to 5 days at each of the two concentrations. A decrease of about 50% was observed.
따라서, 쑥추출물이 Th17 세포의 분화를 억제함으로써 뇌척수염의 발병 빈도 및 증상을 완화하는 효과가 있으며 EAE 역시 쑥추출물에 의해 치료될 수 있음을 시사한다.Therefore, mugwort extracts have an effect of alleviating the differentiation of Th17 cells to alleviate the incidence and symptoms of encephalomyelitis and suggest that EAE can also be treated by mugwort extracts.
<실험예 4> 류마티스 관절염 치료 효과 검토Experimental Example 4 Review of Rheumatoid Arthritis Treatment Effect
Th17 세포에 의해 매개되는 대표적인 자가면역질환인 류마티스 관절염에 대한 치료 효과를 알아보기 위해, 콜라젠에 의해 유도된 관절염 모델을 사용하였다. 관절염 유발은 DBA/1J 마우스에 200㎍의 bovine type II 콜라젠을 200 ㎕의CFA에 현탁하여 꼬리 부분의 말단 피하에 주사하였다. 1차 주사 후 3주 뒤에 2차 부스팅을 한 뒤 관절염 진행을 관찰하였다. To investigate the therapeutic effect of rheumatoid arthritis, a representative autoimmune disease mediated by Th17 cells, a collagen-induced arthritis model was used. Arthritis induction was injected into the terminal subcutaneous of the tail portion by suspending 200 μg of bovine type II collagen in 200 μl of CFA in DBA / 1J mice. Three weeks after the first injection, the second boost was followed by the progression of arthritis.
질병의 정도는 Lee SI 등(Arthritis & Rheumatism, 52: 345-53, 2005)의 방법에 준하여 판단하였다. 추출물의 투여는 부스팅한 다음날부터 4주간 50, 100㎎/kg의 농도로 하루 1회씩 복강 투여하면서 관절염의 진행을 조사하였다.The degree of disease was determined according to the method of Lee SI et al. ( Arthritis & Rheumatism , 52: 345-53, 2005). The administration of the extract was administered intraperitoneally once a day at a concentration of 50, 100mg / kg for 4 weeks from the day after the boosting to investigate the progress of arthritis.
다른 자가면역질환에서와 마찬가지로 쑥추출물은 50㎎/㎏의 처리군과 100㎎/㎏의 처리군 모두에서 매우 효과적으로 관절염이 유발되는 것을 억제하는 것이 확인되었다(도 6). As in other autoimmune diseases, mugwort extract was found to effectively inhibit arthritis in both 50 mg / kg and 100 mg / kg treated groups (FIG. 6).
이러한 동물질환모델에 있어서 쑥추출물은 매우 효과적으로 이상 면역 반응을 제어하는 것으로 나타났기 때문에 추출물 자체로도 자가면역질환 치료제임을 확신할 수 있다.In this animal disease model, the mugwort extract has been shown to effectively control the immune response, so the extract itself can be convinced that it is a therapeutic agent for autoimmune diseases.
이하, 본 발명의 쑥추출물을 함유하는 자가면역질환 치료제의 제제예를 설명하나, 본 발명은 이를 한정하고자 함이 아닌 단지 구체적으로 설명하고자 함이다.Hereinafter, the preparation examples of the autoimmune disease therapeutic agent containing the wormwood extract of the present invention, but the present invention is not intended to limit it, but only to explain in detail.
<제제예 1> 주사제의 제조Preparation Example 1 Preparation of Injection
실시예에서 얻어진 쑥추출물 100 mg, 소디움 메타비설파이트 3.0 ㎎, 메틸파라벤 0.8 ㎎, 프로필파라벤 0.1 ㎎ 및 주사용 멸균증류수 적량을 혼합하고 통상의 방법으로 최종 부피가 2㎖이 되도록 제조한 후, 2㎖용량의 앰플에 충전하고 멸균하여 주사제를 제조하였다.Mugwort extract 100 mg, sodium metabisulfite 3.0 mg, methyl paraben 0.8 mg, propyl paraben 0.1 mg and a sterile distilled water for injection were mixed and prepared in a conventional manner to give a final volume of 2 ml, 2 An injection was prepared by filling an ampule with an ampoules and sterilizing it.
<제제예 2> 정제의 제조Preparation Example 2 Preparation of Tablet
실시예에서 얻어진 쑥추출물 200 ㎎, 유당 100 ㎎, 전분 100 ㎎ 및 스테아린 산 마그네슘 적량을 혼합하고 통상의 정제 제조방법에 따라 타정하여 정제를 제조하였다.Mugwort extract 200 mg,
<제제예 3> 캡슐제의 제조Preparation Example 3 Preparation of Capsule
실시예에서 얻어진 쑥추출물 100 ㎎, 유당 50 ㎎, 전분 50 ㎎, 탈크 2 ㎎ 및 스테아린산 마그네슘 적량을 혼합하고 통상의 캡슐제 제조방법에 따라 젤라틴 캡슐에 충전하여 캡슐제를 제조하였다.Mugwort extract 100 mg,
<제제예 4> 건강식품의 제조Preparation Example 4 Preparation of Health Food
실시예에서 얻어진 쑥추출물 200 ㎎, 비타민 혼합물 적량(비타민 A 아세테이트 70 ㎍, 비타민 E 1.0 ㎎, 비타민 B 1 0.13 ㎎, 비타민 B 2 0.15 ㎎, 비타민 B 6 0.5 ㎎, 비타민 B 12 0.2 ㎍, 비타민 C 10 ㎎, 비오틴 10 ㎍, 니코틴산아미드 1.7 ㎎, 엽산 50 ㎍, 판토텐산 칼슘 0.5 ㎎) 및 무기질 혼합물 적량(황산제1철 1.75 ㎎, 산화아연 0.82 ㎎, 탄산마그네슘 25.3 ㎎, 제1인산칼륨 15 ㎎, 제2인산칼슘 55 ㎎, 구연산칼륨 90 ㎎, 탄산칼슘 100 ㎎, 염화마그네슘 24.8 ㎎)을 혼합한 다음 과립을 제조하고 통상의 방법에 따라 건강식품을 제조하였다.Mugwort extract 200 mg obtained in the Example, vitamin mixture (70 μg of vitamin A acetate, 1.0 mg of vitamin E, 0.13 mg of
도 1a 및 도 1b는 염증성 사이토카인인 IL-1β 및 IL-6에 관한 쑥추출물의 억제활성을 나타낸 것이고,1a and 1b shows the inhibitory activity of the mugwort extract with respect to the inflammatory cytokines IL-1β and IL-6,
도 2는 염증성 사이토카인인 IL-1β 및 IL-6에 관한 쑥추출물의 유전자 발현 억제활성을 나타낸 것이고,Figure 2 shows the gene expression inhibitory activity of the mugwort extract on the inflammatory cytokines IL-1β and IL-6,
도 3은 쑥추출물의 IL-23p40 분비 억제활성을 나타낸 것이고,Figure 3 shows the IL-23p40 secretion inhibitory activity of mugwort extract,
도 4는 쑥추출물의 루프스 치료 효과를 나타낸 것이고,Figure 4 shows the effect of lupus treatment of wormwood extract,
도 5는 쑥추출물의 뇌척수염 치료 효과를 나타낸 것이고,Figure 5 shows the effect of wormwood extract encephalomyelitis treatment,
도 6은 쑥추출물의 류마티스 관절염 치료 효과를 나타낸 것이다.Figure 6 shows the effect of wormwood extract rheumatoid arthritis treatment.
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