KR100891488B1 - The pharmaceutical composition containing effective ingredient of Achillea for prevent and treat of hepatitis B virus - Google Patents
The pharmaceutical composition containing effective ingredient of Achillea for prevent and treat of hepatitis B virus Download PDFInfo
- Publication number
- KR100891488B1 KR100891488B1 KR1020070012139A KR20070012139A KR100891488B1 KR 100891488 B1 KR100891488 B1 KR 100891488B1 KR 1020070012139 A KR1020070012139 A KR 1020070012139A KR 20070012139 A KR20070012139 A KR 20070012139A KR 100891488 B1 KR100891488 B1 KR 100891488B1
- Authority
- KR
- South Korea
- Prior art keywords
- yarrow
- achillea
- aai
- extract
- hepatitis
- Prior art date
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- 241000722941 Achillea Species 0.000 title claims description 7
- 241000700721 Hepatitis B virus Species 0.000 title abstract description 23
- 239000004615 ingredient Substances 0.000 title description 2
- 240000000073 Achillea millefolium Species 0.000 claims abstract description 142
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- 208000002672 hepatitis B Diseases 0.000 claims abstract description 23
- 239000004480 active ingredient Substances 0.000 claims abstract description 17
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Abstract
본 발명은 톱풀의 유효성분을 함유하는 B형 간염 예방 및 치료용 약학적 조성물에 관한 것으로서, 아칠리아 속 식물의 추출물, 이의 불용성 침전물 및 이의 활성분획은 B형 간염 바이러스 복제를 저해하며, 세포 독성이 없는 안정한 물질이므로 B형 간염 예방 및 치료용 약학적 조성물로 유용하게 이용될 수 있다.The present invention relates to a pharmaceutical composition for preventing and treating hepatitis B containing an active ingredient of yarrow, the extract of the plant of the genus Achilles, its insoluble precipitate and its active fraction inhibits hepatitis B virus replication, cytotoxicity Since it is a stable substance, it can be usefully used as a pharmaceutical composition for preventing and treating hepatitis B.
아칠리아, 톱풀, B형 간염. Alicia, yarrow, hepatitis B.
Description
도 1은 톱풀의 추출물(AA) 및 불용성 침전물(AAI)을 얻는 과정을 설명한 모식도이다.1 is a schematic diagram illustrating a process of obtaining an extract (AA) and an insoluble precipitate (AAI) of yarrow.
도 2는 톱풀의 불용성 침전물(AAI)로부터 분획(AAI-1, AAI-2, AAI-3)을 얻는 과정을 나타낸 모식도와 음이온 교환 크로마토그래피 결과이다.Figure 2 is a schematic diagram showing the process of obtaining fractions (AAI-1, AAI-2, AAI-3) from the insoluble precipitate (AAI) of the yarrow.
도 3은 톱풀의 활성 분획(AAI-2)의 구성 성분의 분석 결과이다.Figure 3 shows the results of the analysis of the components of the active fraction of yarrow (AAI-2).
도 4는 톱풀의 활성 분획(AAI-2)의 유기산 조성 측정 결과이다.4 is a result of measuring the organic acid composition of the active fraction (AAI-2) of the yarrow.
도 5는 톱풀의 추출물(AA)로부터 에탄올 처리시 활성 분획(AAI-2)의 수득량을 나타낸 모식도이다.5 is a schematic diagram showing the yield of the active fraction (AAI-2) during ethanol treatment from the extract (AA) of the yarrow.
도 6는 톱풀의 추출물(AA), 이의 불용성 침전물(AAI) 및 이의 활성 분획(AAI-2)의 B형 바이러스 e 항원의 생성 억제를 측정한 그래프이다:FIG. 6 is a graph measuring inhibition of the production of type B virus e antigens of extract of AA, its insoluble precipitate (AAI) and its active fraction (AAI-2):
(A) 톱풀의 추출물(AA);(A) extract of yarrow (AA);
(B) 톱풀의 불용성 침전물(AAI); 및(B) insoluble precipitate of yarrow (AAI); And
(C) 톱풀의 불용성 침전물로부터 분리된 분획(AAI-1, AAI-2, AAI-3).(C) Fractions isolated from insoluble precipitate of yarrow (AAI-1, AAI-2, AAI-3).
본 발명은 톱풀의 유효성분을 함유하는 B형 간염 예방 및 치료용 약학적 조성물에 관한 것으로, 더욱 상세하게는 톱풀의 추출물, 이의 불용성 침전물 및 이의 활성 성분을 포함하는 B형 간염 예방 및 치료용 약학적 조성물에 관한 것이다.The present invention relates to a pharmaceutical composition for preventing and treating hepatitis B containing an active ingredient of yarrow, and more particularly, to a pharmaceutical composition for preventing and treating hepatitis B comprising an extract of yarrow, an insoluble precipitate thereof, and an active ingredient thereof. To a red composition.
사람의 B형 간염 바이러스(HBV)는 급성 및 만성 간염을 유발하여, 자기제어성 급성 간염, 전격성 간염 또는 만성 활동성 간염 등의 병으로 진전될 수 있다. 만성 활동성 간염은 발전되어 간경변 및 간암 등을 유발하고, 간부전을 동반하는 심각한 급성으로 악화될 수 있다(Brechot., J. Hepatol., 4, 269-279, 1987). 만성 간염에 감염되었을 때 대부분의 환자들은 지속성 또는 활동성 간염 증세를 보이는 반면 일부 환자들은 증세를 보이지 않는다. 상기 바이러스성 간염의 발병 기전이나 유발인자는 아직까지 명확히 밝혀지지 않은 실정이다. B형 간염 바이러스가 일으킨 간 손상은 숙주의 면역세포가 매개한다는 일부 증거가 제시된 이래(Milich, D. R. et al ., J. Immunol ., 143, 3141-3147, 1989) 간세포 괴사를 유발하는 바이러스 항원과 특정 B세포 및 T 세포의 면역 반응 및 바이러스 단백질의 직접적인 세포 발병 기전 또는 종양 발병 기전에 대한 연구가 집중적으로 이루어졌다(R. Zschke, O. et al ., Nature, 348, 252-254, 1990). 그러나 여전히 환자마다 다양 하게 나타나는 임상경로의 원인은 분명하지 않다.Human hepatitis B virus (HBV) causes acute and chronic hepatitis, which can progress to diseases such as self-controlling acute hepatitis, blunt hepatitis or chronic active hepatitis. Chronic active hepatitis develops, causes cirrhosis and liver cancer, and can be acutely acute with liver failure (Brechot., J. Hepatol ., 4, 269-279, 1987). When infected with chronic hepatitis, most patients show persistent or active hepatitis, while some do not. The pathogenesis or causative factors of the viral hepatitis are not clear yet. Since some evidence has been shown that liver damage caused by the hepatitis B virus is mediated by the host's immune cells (Milich, DR et. al . , J. Immunol . , 143, 3141-3147, 1989) Intensive studies have been conducted on the pathogenic mechanisms of viral antigens that cause hepatocellular necrosis, immune responses of certain B and T cells, and direct or pathogenic mechanisms of viral proteins (R. Zschke). , O. et al ., Nature , 348, 252-254, 1990). However, the causes of the clinical pathways that still vary from patient to patient are not clear.
B형 간염은 그 증세의 심각성 때문에 그 치료에 많은 관심을 갖고 연구되어져 왔다. 현재 몇몇 약물과 백신이 개발되고 또 임상 전실험과 임상 실험에서 좋은 평가를 받았으나 실제 치료제로 적용된 약은 거의 없는 상태로 지금까지 B형 간염 바이러스(HBV)성 간염 환자에게 시행되는 유일한 치료법은 인체 면역 체계에 의존하는 것이다. HBV에 대한 인체 면역 작용은 HBV 입자를 제거하지만 다른 한편으로는 간세포를 파괴하기 때문에 이러한 면역 작용의 부작용으로 치명적인 질환이 유발되기도 한다. 또한 이러한 문제는 질병의 진행을 예측하기 어렵게 하므로 빠르고 효율적인 간염 치료를 위해서는 항바이러스 요법과 면역 치료법을 복합적으로 사용하는 것이 바람직하다. 즉, 바이러스성 간염의 치료된 간세포는 T 임파구(cytotoxic T lymphocyte, CTL)에 의해 파괴되고, 파괴된 간세포에서 방출된 바이러스 입자는 바이러스에 대한 중화 항체를 제거하여 간세포로의 재감염도 막으면서 바이러스의 증식도 억제하여야 한다. Hepatitis B has been studied with great interest in its treatment because of its severity. Currently, several drugs and vaccines have been developed and have received good reviews in preclinical and clinical trials, but few drugs have been applied as actual therapeutics. To date, the only treatment for hepatitis B virus (HBV) hepatitis patients is human immunity. It depends on the system. Human immune action against HBV removes HBV particles, but on the other hand destroys hepatocytes, so side effects of these immune actions can lead to fatal diseases. In addition, since these problems make it difficult to predict disease progression, it is desirable to use a combination of antiviral therapy and immunotherapy for fast and efficient hepatitis treatment. In other words, treated hepatocytes of viral hepatitis are destroyed by cytotoxic T lymphocytes (CTLs), and virus particles released from the destroyed hepatocytes remove the neutralizing antibodies to the virus to prevent reinfection of the hepatocytes. Proliferation should also be suppressed.
B형 간염 바이러스 복제시 3개(c, s, e 항원)의 주요 항원이 만들어지는데 c(core) 항원은 구조적 항원 결정체이며 s(surface) 항원은 바이러스 표면 단백질에 의해 나타나는 항원 결정체이다. e 항원은 B형 간염 바이러스 감염 여부를 알아내는 혈액에서의 표시물질이다. e 항원은 B형 간염의 번식에 필수 조건은 아니며 B형간염 바이러스의 생활사에서의 역할은 아직 확실히 밝혀져 있지 않다. 그러나 e 항원의 유전자가 유사 동물 바이러스에서 보존된 것으로 미루어 볼 때 상기 항원이 중요한 역할을 수행하리라는 것이 추측되고 있다. 따라서 e 항원은 바이러 스를 제거하기 위한 면역학적인 목표물로서, 특히 숙주가 바이러스를 제거하는데 중요한 역할을 한다(Pignatelli, M. et al., J. Hepal . 4, 15-16. 1987)Hepatitis B virus replication produces three major antigens (c, s and e antigens), the c (core) antigen is a structural antigen crystal and the s (surface) antigen is an antigenic crystal that is represented by viral surface proteins. The e antigen is a marker in the blood to detect hepatitis B virus infection. The e antigen is not a prerequisite for the propagation of hepatitis B and its role in the life history of the hepatitis B virus is not yet clear. However, it is speculated that the antigen plays an important role in view of the conserved gene of the e antigen. Thus, the e antigen is an immunological target for removing viruses, and in particular plays an important role in removing the virus from the host (Pignatelli, M. et al., J. Hepal . 4, 15-16. 1987).
B형 간염 바이러스(HBV)에 의한 만성 간염은 전 세계적으로 약 3억의 인구가 감염되어 있어 세계적인 의료 관심의 대항이 되어 왔으나, 대부분의 바이러스 질환에서와 마찬가지로 항 HBV 의약품도 개발되어 사용되는 제품이 많지 않아 임상 의사들이 간염 등을 치료하는데 곤란을 겪고 있다. 실제로 바이러스학은 상당히 발전되어 HBV를 포함한 인체에 질병을 일으키는 대부분 바이러스의 증식 과정이 잘 밝혀져 있는데, 현재는 이를 토대로 병원성 바이러스에 대한 치료제를 개발하려는 경쟁이 치열해지고 있다. 지금까지 사용된 항바이러스 제제는 주로 뉴클레오타이드 유도체(nucleotide analogue)를 이용하여 개발된 제품이지만, 이외에도 천연물로부터 새로운 물질을 얻어 항바이러스 제제를 생산 할 수 있다면, 제약산업 뿐만 아니라 다른 생물학 분야에도 광범위하게 이용될 것으로 보인다. Chronic hepatitis caused by hepatitis B virus (HBV) has been around the world's medical interests due to the infection of about 300 million people worldwide.However, as in most viral diseases, anti-HBV medicines have been developed and used. Not many clinicians are having trouble treating hepatitis. Indeed, virology has advanced so much that the proliferation of most viruses that cause disease in humans, including HBV, is well documented, and now there is a lot of competition to develop therapeutics for pathogenic viruses. The antiviral agents used so far have mainly been developed using nucleotide analogues, but if they can be produced from natural substances and produce antiviral agents, they are widely used not only in the pharmaceutical industry but also in other biological fields. Seems to be.
최근 식물유래 천연물이 B형 간염 바이러스의 복제 또는 라이프 싸이클(life cycle)의 각 단계를 억제하여 항바이러스 효과를 찾으려하는 시도가 많이 일어나고 있다. 그러나 구체적인 항바이러스 물질에 대한 분리 및 작용 기작에 대하여는 현재까지 명확하게 밝혀진 것이 없는 실정이다. Recently, many attempts have been made to find antiviral effects by inhibiting each step of the hepatitis B virus replication or life cycle. However, the mechanism of isolation and action on specific antiviral substances has not been clearly understood to date.
톱풀(Achillea alpina L)은 국화과에 속하는 식물로서, 한약재명으로는 일지호(一枝蒿)라고 불리우며 가새풀, 배암세, 배암체라고 불리기도 한다. 형태학적으로 국화과에 속하는 톱풀은 형태학적으로 다음과 같은 특징을 지니고 있다. 잎은 어긋나며 잎자루는 없고 끝이 둔하며 길이 6-10 cm, 폭은 7-15 mm로서 밑부분이 원줄기를 얼싸안고 빗살처럼 갈라지며 열편은 긴 타원상 창모양으로서 뾰족한 톱니가 있고 갈라지지 않은 중앙열편은 나비 1-3 mm이다. 열매인 수과는 길이 3 mm, 폭은 1 mm로서 양끝이 납작하고 털이 없다. 꽃은 7-10월에 피며 홍색이나 백색이고 직경 7-9 mm로서 가지 끝과 원줄기 끝의 산방꽃차례에 달리고 꽃차례받침은 구상 종형이며 길이와 폭이 각각 5 mm로서 털이 약간 있고 포조각은 2줄로 배열되며 외편이 보다 짧고 긴 타원형이다. 암꽃은 5-7개이며, 꽃부리는 길이가 3.5-4.5mm, 폭은 2.5-3 mm이고, 통 모양의 부위는 길이 1.5 mm이며, 양성화의 꽃부리는 길이가 2.3 mm 이다. 줄기는 높이가 50-110 cm이고 곧게 자라며 한곳에서 여러대가 자란다. 밑 부분에는 털이 없고 윗부분에는 털이 많다. 땅속줄기는 옆으로 뻗고 잔뿌리가 많이 뻗는다. 한국, 일본, 사할린, 만주, 중국 북부, 시베리아, 캄차카에 분포하고 전국의 산야에서 흔히 분포한다. 숙근성 여러해살이풀로 관하식물의 형태를 띄며, 높이는 50-110 cm이다. 7월과 8월 사이에 수확한 꽃과 5월과 6월 사이에 수확한 잎을 사용하여 추출한다. 함유성분으로는 에테르오일, 플라빈, 아줄렌(Azulen, 탄수화물의 일종, 특히 케모마일의 에테르오일에 함유되어 있다. 톱풀은 성질이 따뜻하고 맛은 약간 쓰며, 심경, 간경, 폐경에 작용한다. 피를 잘 돌게 하고 풍을 없애며 아픔을 멎게 하고 독을 푼다. 특히 뱀에 물렸을 때 날것을 짓찧어서 물린 부위에 붙이면 부기가 내리고 독이 빠진다. 서양톱풀은 간세포에서 담즙이 잘 나오도록 하며 항균작용과 염증완화 작용이 있다. 또한 수렴작용을 하기도 하고 경련을 해소하는 작용을 하기도 한다. 서양톱풀은 식용부인이나 위장장애 그리고 위장의 가벼운 경련증상에 좋은 효과가 있다. 외용으로는 여성의 하복부에 통증이 수반되는 신경성 경련과 월경통을 해소하는데 좌욕의 재료로 이용할 수 있으며, 간의 만성질환에 따뜻한 습포를 대면 오른쪽 상복부에 나타나는 복부 팽만감을 완화할 수 있다. Yarrow ( Achillea alpina L) is a plant belonging to the Asteraceae family. Morphologically belonging to the Asteraceae family, Yarrow has the following characteristics. Leaves are alternate, no petioles, dull, 6-10 cm long, 7-15 mm wide, with the lower part enclosing the main stem and split like combs. The lobes are long oval-shaped lanceolate with pointed sawtooth and unbranched center. Lobes are 1-3 mm in width. Fruit is a fruit, 3 mm long, 1 mm wide, flat on both ends and hairless. Flowers bloom in July-October, red or white, 7-9 mm in diameter, hang on the end of branch and main stem, and inflorescences are globose, 5 mm in length and width, with a few hairs and two pieces of shells arranged. The outer side is shorter and longer oval. Female flowers 5-7, beak 3.5-4.5mm long, 2.5-3 mm wide, tubular part 1.5mm long, and peduncle is 2.3 mm long. Stems are 50-110 cm high, grow straight, and grow several in one place. There is no hair at the bottom and there is a lot of hair at the top. Underground stem extends to the side and many roots are extended. It is distributed in Korea, Japan, Sakhalin, Manchuria, northern China, Siberia, and Kamchatka, and it is common in the mountains and mountains of the country. It is a perennial herbaceous plant, shaped like a plant, with a height of 50-110 cm. Extracted using flowers harvested between July and August and leaves harvested between May and June. Consists of ether oils, flavin and azulene (Azulen, a kind of carbohydrates, especially chemomile ether oil.) Yarrow is warm in nature and slightly bitter, and works on heart, liver and menopause. It turns well, removes the wind, relieves pain and squeezes the poison, especially when the snake bites, crushes the raw material and attaches it to the bite area so that swelling and venom are lost. It also acts as a convergent and relieving spasm Yarrow is effective for edible women, gastrointestinal disorders and mild cramps in the stomach. It can be used as a material for the left bath to relieve cramps and dysmenorrhea. Tana can alleviate bloating.
이에 본 발명자들은 톱풀(Achilla) 속 식물의 추출물 및 그의 유효성분이 B형 간염 바이러스의 예방 및 치료에 효과적임을 확인함으로써 본 발명을 완성하였다.The present inventors completed the present invention by confirming that the extract of the plant of the genus Achilla and its active ingredient is effective in the prevention and treatment of hepatitis B virus.
본 발명은 아칠리아(Achillea)속 식물의 추출물, 이의 불용성 침전물 또는 이의 활성분획을 유효성분으로 포함하는 간염 예방 및 치료용 약학적 조성물을 제공한다.The present invention provides a pharmaceutical composition for preventing and treating hepatitis comprising an extract of the genus Achillea , an insoluble precipitate thereof or an active fraction thereof as an active ingredient.
상기 목적을 달성하기 위하여, 본 발명은 아칠리아속 식물의 추출물(AA), 상기 추출물을 저급 알코올에 용해하여 생성된 불용성 침전물(AAI) 또는 상기 불용성 침전물(AAI)을 크로마토그래피를 이용하여 분리한 활성 분획(AAI-2)을 유효성분으로 함유하는 B형 간염 예방 및 치료용 약학적 조성물을 제공한다.In order to achieve the above object, the present invention is to extract the insoluble precipitate (AAI) or the insoluble precipitate (AAI) produced by dissolving the extract (AA), the extract in a lower alcohol of the genus Achilles plants It provides a pharmaceutical composition for the prevention and treatment of hepatitis B containing the active fraction (AAI-2) as an active ingredient.
또한, 본 발명은 상기 약학적 조성물을 유효성분으로 함유하는 B형 간염 치료제를 제공한다.The present invention also provides a hepatitis B therapeutic agent containing the pharmaceutical composition as an active ingredient.
또한, 본 발명은 아칠리아속 식물의 추출물(AA), 상기 추출물을 저급 알코올에 용해하여 생성된 불용성 침전물(AAI) 또는 상기 불용성 침전물(AAI)을 크로마토그래피를 이용하여 분리한 활성 분획(AAI-2)을 유효성분으로 함유하는 B형 간염 예방용 건강식품을 제공한다.In addition, the present invention is an extract of AA genus (AA), an insoluble precipitate (AAI) produced by dissolving the extract in a lower alcohol or the active fraction (AAI-) separated by chromatography using an insoluble precipitate (AAI). Provides a hepatitis B preventive health food containing 2) as an active ingredient.
아울러, 아칠리아속 식물로부터 항 B형 간염 바이러스 성분을 포함하는 약학적 조성물 제조 방법을 제공한다.In addition, the present invention provides a method for preparing a pharmaceutical composition comprising an anti-hepatitis B virus component from the genus Acilia.
이하 본 발명을 상세히 설명한다.Hereinafter, the present invention will be described in detail.
본 발명은 아칠리아속 식물의 추출물(AA)을 유효성분으로 함유하는 B형 간염 예방 및 치료용 약학적 조성물을 제공한다.The present invention provides a pharmaceutical composition for the prevention and treatment of hepatitis B containing an extract of the genus Achilles plants (AA) as an active ingredient.
상기 아칠리아속 식물로는 큰톱풀(Achilla ptarmica subsp. macrocephala var. angustifolia Heim), 큰톱풀[Achillea acuminata (Lebeb.) Sch. Bio], 큰톱풀(Achillea acuminata Freyn), 톱풀(Achillea alpina L.), 붉은톱풀[Achillea alpina subsp. rhodoptarmica (Nakai) Kitam], 산톱풀[Achillea alpina var, discoidea (Regal) Kitam], 서양톱풀(Achillea millefolium L.), 털톱풀[Achillea millefolium var. setacea (Waldst & Koch)], 큰톱풀(Achillea ptarmica L.), 큰톱풀[Achillea ptarmica var. acuminata (Ledeb.) Heim], 산톱풀(Achillea ptarmicoides Naxim.), 붉은톱풀(Achilla rhodoptarmica Nakai), 털톱풀(Achilla setacea Waldst & Kit), 톱풀(Achillea sibirica Ledet.), 및 산톱풀(Achillea sibirica Var. discoidea Regal)인 것을 특징으로 한다. 본 발명의 추출물(AA)은 물, 알코올 또는 이들의 혼합용매를 추출용매를 이용하는 것이 바람직하며, 알코올로는 C1 내지 C4 저급 알코올을 이용하는 것이 바람직하며, 저급 알코올로는 에탄올 또는 메탄올을 이용하는 것이 바람직하다. 본 발명의 실시예에서는 톱풀(Achillea alpina)을 열수 추출하였다. 열수 추출시 증류수를 건조된 톱풀 분량에 1 내지 10배 첨가하여 추출하는 것이 바람직하며, 2배 첨가하여 추출하는 것이 더욱 바람직하다. 또한 50 내지 100℃에서 추출하는 것이 바람직하며, 60℃에서 추출하는 것이 더욱 바람직하에 한정되는 것은 아니다. 아울러 추출 회수는 1 내지 5회인 것이 바람직하며, 2회 반복 추출하는 것이 더욱 바람직하나 이에 한정되는 것은 아니다. 상기 톱풀의 추출물(AA)을 이용하여 B형 간염 바이러스 e 항원의 생성에 미치는 영향을 조사한 결과, 낮은 농도로 처리하여도 e 항원의 활성을 감소시킴을 확인하였다(도 6a 참조). Examples of the genus Acyl include Achilla ptarmica subsp. Macrocephala var. Angustifolia Heim , and Achillea acuminata (Lebeb.) Sch. Bio ], yarrow ( Achillea acuminata Freyn ), yarrow ( Achillea alpina L. ), red yarrow [ Achillea alpina subsp. rhodoptarmica (Nakai) Kitam ], mountain yarrow [ Achillea alpina var, discoidea (Regal) Kitam ], yarrow ( Achillea millefolium L. ), yarrow [ Achillea millefolium var. setacea (Waldst & Koch) ], Yarrow ( Achillea ptarmica L. ), Yarrow [ Achillea ptarmica var. acuminata (Ledeb.) Heim], mountain yarrow (Achillea ptarmicoides Naxim.), red yarrow (Achilla rhodoptarmica Nakai), Hair yarrow (Achilla setacea Waldst & Kit), yarrow (Achillea sibirica Ledet.), and acid Yarrow (Achillea sibirica Var discoidea Regal ). Extract (AA) of the present invention is preferably water, alcohol or a mixed solvent thereof using an extraction solvent, it is preferable to use a C 1 to C 4 lower alcohol, alcohol using ethanol or methanol as a lower alcohol It is preferable. In an embodiment of the present invention, yarrow ( Achillea alpina ) was extracted with hot water. During hot water extraction, distilled water is preferably extracted by adding 1 to 10 times the amount of dried yarrow, and more preferably by adding 2 times. Moreover, it is preferable to extract at 50-100 degreeC, and to extract at 60 degreeC is not limited to a more preferable thing. In addition, the number of extraction is preferably 1 to 5 times, more preferably two times extraction is not limited thereto. As a result of investigating the effect on the production of hepatitis B virus e antigen using the extract (AA) of the yarrow, it was confirmed that even if the treatment at a low concentration reduced the activity of the e antigen (see Figure 6a).
또한, 본 발명은 상기 아칠리아속 식물의 추출물(AA)을 저급 알코올에 용해하여 생성된 불용성 침전물(AAI)을 유효성분으로 함유하는 간염 예방 및 치료용 약학적 조성물을 제공한다.In addition, the present invention provides a pharmaceutical composition for preventing and treating hepatitis, which contains an insoluble precipitate (AAI) produced by dissolving the extract of the genus Achilles plant (AA) in a lower alcohol.
본 발명의 불용성 침전물(AAI)은 상기 제조된 아칠리아속 식물의 추출물(AA)을 대상으로 저급 알코올로 용해하여 수득할 수 있으며, 상기 저급 알코올은 메탄 올인 것이 바람직하다. 본 발명의 실시예에서는 상기 추출물(AA)을 100% 메탄올로 용해한 후 원심분리를 수행하여 가용성 분획(AAS)와 불용성 침전물(AAI)을 분리하여 수득하였다. 수득된 불용성 침전물(AAI)을 이용하여 B형 간염 바이러스 e 항원의 생성에 미치는 영향을 조사한 결과, 낮은 농도로 처리하여도 e 항원의 활성을 감소시킴을 확인하였다(도 6b 참조). Insoluble precipitate (AAI) of the present invention can be obtained by dissolving the extract (AA) of the Achilles plants prepared above with a lower alcohol, the lower alcohol is preferably methanol. In the embodiment of the present invention was obtained by dissolving the extract (AA) in 100% methanol and centrifugation to separate the soluble fraction (AAS) and insoluble precipitate (AAI). As a result of investigating the effect on the production of hepatitis B virus e antigen by using the obtained insoluble precipitate (AAI), it was confirmed that the activity of e antigen is reduced even at low concentrations (see Fig. 6b).
또한, 본 발명은 상기 불용성 침전물(AAI)을 크로마토그래피를 이용하여 분획한 분획(AAI-1, AAI-2, AAI-3) 중 AAI-2를 유효성분으로 함유하는 간염 예방 및 치료용 약학적 조성물을 제공한다.In addition, the present invention is a pharmaceutical for preventing and treating hepatitis containing AAI-2 as an active ingredient in fractions (AAI-1, AAI-2, AAI-3) fractionated by chromatography of the insoluble precipitate (AAI). To provide a composition.
본 발명자들은 상기 불용성 침전물(AAI)을 크로마토그래피를 이용하여 활성 분획을 수득하였다. 상기 크로마토그래피로는 음이온 교환 크로마토그래피이며, DEAE-셀룰로오스 레진을 이용하는 것이 바람직하다. 본 발명의 본 발명자들은 0.1 M, 0.3 M, 0.5 M NaCl 및 1 N NaOH를 이용하여 이온 세기에 따른 활성 분획을 수득하였다. 그 결과 3개의 활성분획(AAI-1, AAI-2, AAI-3)을 수득하였다(도 2 참조). 상기 3개의 활성 분획을 이용하여 B형 간염 바이러스 e 항원의 생성에 미치는 영향을 조사한 결과, AAI-1, AAI-2, AAI-3 모두 e 항원의 활성을 감소시켰으며, 이 중 AAI-2는 양성 대조군과 같은 효과를 가지고 e 항원의 활성을 감소시킴을 확인하였다(도 6c 참조). 본 발명의 활성 분획(AAI-2)은 만노오스, 갈락토오스 및 글루코오스와 같은 당으로 구성되어 있으며(도 3 참조), 유기산 조성 측정 결과 주요 유기산으로 옥살산으로 구성되어 있음을 확인하였다(도 4 참조). We obtained the active fraction by chromatography on the insoluble precipitate (AAI). As said chromatography, it is anion exchange chromatography, and it is preferable to use DEAE-cellulose resin. The inventors of the present invention obtained the active fraction according to the ionic strength using 0.1 M, 0.3 M, 0.5 M NaCl and 1 N NaOH. As a result, three active fractions (AAI-1, AAI-2, AAI-3) were obtained (see FIG. 2). As a result of investigating the effect on the production of hepatitis B virus e antigen using the three active fractions, all of the AAI-1, AAI-2, AAI-3 reduced the e antigen activity, of which AAI-2 It was confirmed to reduce the activity of the e antigen with the same effect as the positive control (see Figure 6c). The active fraction of the present invention (AAI-2) is composed of sugars such as mannose, galactose, and glucose (see FIG. 3), and the organic acid composition was confirmed to be composed of oxalic acid as the main organic acid (see FIG. 4).
본 발명의 간염 예방 및 치료용 약학적 조성물은 상기 톱풀 추출물(AA), 이의 불용성 침전물(AAI) 및 활성 분획(AAI-2)에서 하나 이상을 선택적으로 함유할 수 있으며, 상기 성분에 추가로 동일 또는 유사한 기능을 나타내는 유효성분을 1종 이상 함유할 수 있다.The pharmaceutical composition for the prevention and treatment of hepatitis of the present invention may optionally contain one or more in the yarrow extract (AA), its insoluble precipitate (AAI) and active fraction (AAI-2), and in addition to the above components Or it may contain one or more active ingredients exhibiting similar functions.
본 발명의 톱풀 추출물(AA), 이의 불용성 추출물(AAI) 및 활성 분획(AAI-2)은 임상 투여 시에 경구 또는 비경구로 투여가 가능하며 일반적인 의약품 제제의 형태로 사용될 수 있다. 즉, 본 발명의 간염 예방 및 치료용 약학적 조성물은 실제 임상 투여 시에 경구 및 비경구의 여러 가지 제형으로 투여될 수 있는데, 제제화할 경우에는 보통 사용하는 충진제, 증량제, 결합제, 습윤제, 붕해제 및 계면활성제 등의 희석제 또는 부형제를 사용하여 조제된다. 경구 투여를 위한 고형 제제에는 정제, 환제, 산제, 과립제 및 캡슐제 등이 포함되며, 이러한 고형 제제는 본 발명의 약학적 조성물에 적어도 하나 이상의 부형제 예를 들면, 전분, 탄산칼슘, 수크로스, 락토오스 및 젤라틴 등을 섞어 조제된다. 또한 단순한 부형제 이외에 마그네슘 스티레이트 탈크 같은 윤활제들도 사용된다. 경구 투여를 위한 액상 제제로는 현탁제, 내용액제, 유제 및 시럽제 등이 해당되는데 흔히 사용되는 단순 희석제인 물, 리퀴드 파라핀 이외에 여러 가지 부형제, 예를 들면 습윤제, 감미제, 방향제 및 보존제 등이 포함될 수 있다. 비경구 투여를 위한 제제에는 멸균된 수용액, 비수성용제, 현탁제, 유제, 동결건조제제 및 좌제가 포함된다. 비수성용제와 현탁용제로는 프로필렌글리콜, 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, 글리세롤 및 젤라틴 등이 사용될 수 있다. 본 발명의 약학적 조성물은 비경구 투여시 피하주사, 정맥주사 또는 근육내 주사를 통할 수 있다. Yarrow extract (AA), its insoluble extract (AAI) and active fraction (AAI-2) of the present invention can be administered orally or parenterally during clinical administration and can be used in the form of general pharmaceutical formulations. That is, the pharmaceutical composition for preventing and treating hepatitis of the present invention may be administered in various oral and parenteral dosage forms in actual clinical administration, and when formulated, the commonly used fillers, extenders, binders, wetting agents, disintegrants and It is prepared using diluents or excipients such as surfactants. Solid preparations for oral administration include tablets, pills, powders, granules and capsules, and the like, which may be used in the pharmaceutical composition of the present invention at least one excipient such as starch, calcium carbonate, sucrose, lactose And gelatin etc. are mixed and prepared. In addition to simple excipients, lubricants such as magnesium styrate talc are also used. Liquid preparations for oral administration include suspensions, solutions, 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. have. Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations and suppositories. As the non-aqueous solvent and the suspension solvent, 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, glycerol and gelatin may be used. The pharmaceutical composition of the present invention may be via subcutaneous injection, intravenous injection or intramuscular injection during parenteral administration.
투약 단위는, 예를 들면 개별 투약량의 1, 2, 3 또는 4배를 함유하거나 또는 1/2, 1/3 또는 1/4배를 함유할 수 있다. 개별 투약량은 바람직하기로는 유효 약물이 1회에 투여되는 양을 함유하며, 이는 통상 1일 투여량의 전부, 1/2, 1/3 또는 1/4배에 해당한다. 본 발명의 약학적 조성물의 유효용량은 0.0001 ~ 10 g/㎏이고, 바람직하기로는 0.0001 g ~ 5 g/kg이며, 하루 1~6회 투여될 수 있다.Dosage units may contain, for example, one, two, three or four times the individual dosage, or they may contain 1/2, 1/3 or 1/4 times. The individual dosage preferably contains an amount in which the effective drug is administered at one time, which usually corresponds to all, 1/2, 1/3 or 1/4 times the daily dose. The effective dose of the pharmaceutical composition of the present invention is 0.0001 to 10 g / kg, preferably 0.0001 g to 5 g / kg, may be administered 1 to 6 times a day.
본 발명의 간염 예방 및 치료용 약학적 조성물을 랫트에 경구 투여하여 독성 실험을 수행한 결과, 경구 투여 독성시험에 의한 50% 치사량(LD50)은 적어도 5 g/kg 이상인 안전한 물질로 판단된다. 본 발명의 간염 예방 및 치료용 약학적 조성물은 B형 간염의 예방 및 치료를 위하여 단독으로, 또는 수술, 호르몬 치료, 화학 치료 및 생물학적 반응 조절제를 사용하는 방법들과 병용하여 사용할 수 있다.As a result of toxicity experiments by orally administering the pharmaceutical composition for preventing and treating hepatitis of the present invention, 50% lethal dose (LD 50 ) by oral administration toxicity test is determined to be a safe substance of at least 5 g / kg or more. The pharmaceutical composition for preventing and treating hepatitis B of the present invention may be used alone or in combination with methods using surgery, hormone therapy, chemotherapy and biological response modifiers for the prevention and treatment of hepatitis B.
또한, 본 발명은 아칠리아속 식물의 추출물(AA), 상기 추출물을 저급 알코올에 용해하여 생성된 불용성 침전물(AAI) 또는 상기 불용성 침전물(AAI)을 크로마토그래피를 이용하여 분리한 활성 분획(AAI-2)을 유효성분으로 함유하는 간염 예방용 건강식품을 제공한다.In addition, the present invention is an extract of AA genus (AA), an insoluble precipitate (AAI) produced by dissolving the extract in a lower alcohol or the active fraction (AAI-) separated by chromatography using an insoluble precipitate (AAI). Provides a hepatitis preventive health food containing 2) as an active ingredient.
본 발명의 아칠리아속 식물의 추출물(AA), 상기 추출물을 저급 알코올에 용 해하여 생성된 불용성 침전물(AAI) 또는 상기 불용성 침전물(AAI)을 크로마토그래피를 이용하여 분리한 활성 분획(AAI-2)을 식품 첨가물로 사용할 경우, 상기 아칠리아속 식물의 추출물(AA), 상기 추출물을 저급 알코올에 용해하여 생성된 불용성 침전물(AAI) 또는 상기 불용성 침전물(AAI)을 크로마토그래피를 이용하여 분리한 활성 분획(AAI-2)을 그대로 첨가하거나 다른 식품 또는 식품 성분과 함께 사용될 수 있고, 통상적인 방법에 따라 적절하게 사용될 수 있다. 또한 아칠리아속 식물의 추출물(AA)에 에탄올을 용하여 활성 분획(AAI-2)를 수득할 수 있으며, 상기 에탄올의 농도는 30 내지 90%인 것이 바람직하다. 유효 성분의 혼합양은 사용 목적(예방, 건강 또는 치료적 처치)에 따라 적합하게 결정될 수 있다. 일반적으로, 식품 또는 음료의 제조시에 본 발명의 약학적 조성물은 원료에 대하여 15 중량부 이하, 바람직하게는 10 중량부 이하의 양으로 첨가된다. 그러나 건강 및 위생을 목적으로 하거나 또는 건강 조절을 목적으로 하는 장기간의 섭취의 경우에는 상기 양은 상기 범위 이하일 수 있으며, 안전성 면에서 아무런 문제가 없기 때문에 유효성분은 상기 범위 이상의 양으로도 사용될 수 있다.Extract (AA) of the genus Achilles plant of the present invention, the active fraction obtained by dissolving the extract in lower alcohol (AAI) or the insoluble precipitate (AAI) using chromatography (AAI-2) ) Is used as a food additive, the activity of the insoluble precipitate (AAI) or the insoluble precipitate (AAI) produced by dissolving the extract of the genus Aalicia, the extract in a lower alcohol using chromatography Fraction (AAI-2) may be added as such or used with other foods or food ingredients, and may be appropriately used according to conventional methods. In addition, the active fraction (AAI-2) may be obtained by using ethanol in the extract of the genus Achilles (AA), and the concentration of the ethanol is preferably 30 to 90%. The mixed amount of the active ingredient may be suitably determined depending on the purpose of use (prevention, health or therapeutic treatment). Generally, in the preparation of food or beverages, the pharmaceutical compositions of the present invention are added in an amount of up to 15 parts by weight, preferably up to 10 parts by weight based on the raw materials. However, in the case of long-term intake for health and hygiene or health control purposes, the amount may be below the above range, and the active ingredient may be used in an amount above the above range because there is no problem in terms of safety.
상기 식품의 종류에는 특별한 제한은 없다. 상기 물질을 첨가할 수 있는 식품의 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 등이 있으며, 통상적인 의미에서의 건강식품을 모두 포함한다.There is no particular limitation on the kind of food. Examples of the food to which the substance can be added include dairy products including meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, gums, ice cream, various soups, drinks, tea, drinks, Alcoholic beverages and vitamin complexes, and the like and include all of the health foods in the conventional sense.
본 발명의 건강음료 조성물은 통상의 음료와 같이 여러 가지 향미제 또는 천 연 탄수화물 등을 추가 성분으로서 함유할 수 있다. 상술한 천연 탄수화물은 포도당, 과당과 같은 모노사카라이드, 말토스, 슈크로스와 같은 디사카라이드, 및 덱스트린, 사이클로덱스트린과 같은 폴리사카라이드, 자일리톨, 소르비톨, 에리트리톨 등의 당알콜이다. 감미제로서는 타우마틴, 스테비아 추출물과 같은 천연 감미제나, 사카린, 아스파르탐과 같은 합성 감미제 등을 사용할 수 있다. 상기 천연 탄수화물의 비율은 본 발명의 약학적 조성물 100 ㎖당 일반적으로 약 0.01~0.04 g, 바람직하게는 약 0.02~0.03 g 이다.The health beverage composition of the present invention may contain various flavors, natural carbohydrates, and the like as additional components, as in general beverages. The above-mentioned natural carbohydrates are glucose, monosaccharides such as fructose, disaccharides such as maltose and sucrose, and polysaccharides such as dextrin and cyclodextrin, sugar alcohols such as xylitol, sorbitol and erythritol. As the sweetening agent, natural sweetening agents such as tautin and stevia extract, synthetic sweetening agents such as saccharin and aspartame, and the like can be used. The ratio of the natural carbohydrate is generally about 0.01 to 0.04 g, preferably about 0.02 to 0.03 g per 100 ml of the pharmaceutical composition of the present invention.
상기 외에 본 발명의 아칠리아속 식물의 추출물(AA), 상기 추출물을 저급 알코올에 용해하여 생성된 불용성 침전물(AAI) 또는 상기 불용성 침전물(AAI)을 크로마토그래피를 이용하여 분리한 활성 분획(AAI-2)은 여러가지 영양제, 비타민, 전해질, 풍미제, 착색제, 펙트산 및 그의 염, 알긴산 및 그의 염, 유기산, 보호성 콜로이드 증점제, pH 조절제, 안정화제, 방부제, 글리세린, 알콜, 탄산 음료에 사용되는 탄산화제 등을 함유할 수 있다. 그밖에 본 발명의 아칠리아속 식물의 추출물(AA), 상기 추출물을 저급 알코올에 용해하여 생성된 불용성 침전물(AAI) 또는 상기 불용성 침전물(AAI)은 천연 과일쥬스, 과일쥬스 음료 및 야채 음료의 제조를 위한 과육을 함유할 수 있다. 이러한 성분은 독립적으로 또는 조합하여 사용할 수 있다. 이러한 첨가제의 비율은 크게 중요하진 않지만 본 발명의 혈당 강하용 조성물 100 중량부 당 0.01~0.1 중량부의 범위에서 선택되는 것이 일반적이다.In addition to the extract of the genus Achilles plants of the present invention, the insoluble precipitate (AAI) or the insoluble precipitate (AAI) produced by dissolving the extract in lower alcohol using chromatography (AAI- 2) is used in various nutrients, vitamins, electrolytes, flavors, colorants, pectic acid and salts thereof, alginic acid and salts thereof, organic acids, protective colloidal thickeners, pH regulators, stabilizers, preservatives, glycerin, alcohols, carbonated drinks Carbonating agent and the like. In addition, the extract of AA genus plants of the present invention, the insoluble precipitate (AAI) or the insoluble precipitate (AAI) produced by dissolving the extract in a lower alcohol is prepared for the production of natural fruit juice, fruit juice beverage and vegetable beverage. May contain pulp. These components can be used independently or in combination. Although the ratio of such an additive is not critical, it is generally selected from the range of 0.01 to 0.1 parts by weight per 100 parts by weight of the blood glucose lowering composition.
아울러 본 발명은 아칠리아속 식물로부터 항 B형 간염 바이러스 성분을 포함 하는 약학적 조성물 제조 방법을 제공한다.In addition, the present invention provides a method for preparing a pharmaceutical composition comprising an anti-hepatitis B virus component from the genus Acilia.
상기 제조방법은 하기와 같다: 1) 건조한 아칠리아속 식물 시료를 열수 추출하는 단계; 2) 단계 1)의 아칠리아속 식물의 열수 추출물을 감압농축하는 단계; 3) 단계 2)의 감압농축액을 물, 저급 알코올 또는 이들의 혼합물에 용해시키는 단계; 4) 단계 3)의 용해물은 가용성 분획과 불용성 침전물로 분리하는 단계; 5) 단계 4)의 불용성 침전물은 크로마토그래피 방법을 통해 활성 분획을 수득하는 단계.The preparation method is as follows: 1) extracting hot water from a dry acyl plant sample; 2) depressurizing the hydrothermal extract of the genus Acyl plant of step 1); 3) dissolving the vacuum concentrate of step 2) in water, lower alcohol or a mixture thereof; 4) separating the lysate of step 3) into a soluble fraction and an insoluble precipitate; 5) Insoluble precipitate of step 4) is obtained by the chromatography method to obtain an active fraction.
상기 제조 방법에 있어서, 단계 1)의 아칠리아속 식물은 큰톱풀(Achilla ptarmica subsp. macrocephala var . angustifolia Heim), 큰톱풀[Achillea acuminata (Lebeb.) Sch . Bio], 큰톱풀(Achillea acuminata Freyn), 톱풀(Achillea alpina L.), 붉은톱풀[Achillea alpina subsp . rhodoptarmica ( Nakai ) Kitam], 산톱풀[Achillea alpina var , discoidea ( Regal ) Kitam], 서양톱풀(Achillea millefolium L.), 털톱풀[Achillea millefolium var . setacea ( Waldst & Koch )], 큰톱풀(Achillea ptarmica L.), 큰톱풀[Achillea ptarmica var . acuminata (Ledeb.) Heim], 산톱풀(Achillea ptarmicoides Naxim.), 붉은톱풀(Achilla rhodoptarmica Nakai), 털톱풀(Achilla setacea Waldst & Kit), 톱풀(Achillea sibirica Ledet .), 및 산톱풀(Achillea sibirica Var . discoidea Regal)인 것을 특징으로 한다.In the above production method, the genus Acyl plants of step 1) may be Achilla ptarmica subsp. macrocephala var . angustifolia Heim ), A chillea acuminata (Lebeb.) Sch . Bio , Achillea acuminata Freyn ), Yarrow ( Achillea alpina L. ), Yarrow [A chillea alpina subsp . rhodoptarmica ( Nakai ) Kitam ], Yarrow [ Achillea alpina var , discoidea ( Regal ) Kitam ], Yarrow ( Achillea millefolium L. ), Yarrow [ Achillea millefolium var . setacea ( Waldst & Koch ) ], Yarrow ( Achillea ptarmica L. ), yarrow [ Achillea ptarmica var . acuminata (Ledeb.) Heim ], Achillea ptarmicoides Naxim .), Red yarrow ( Achilla rhodoptarmica Nakai ), yarrow ( Achilla setacea Waldst & Kit ), yarrow ( Achillea sibirica Ledet . ), And mountain yarrow ( Achillea) sibirica Var . discoidea Regal ).
상기 제조 방법에 있어서, 단계 3)의 저급 알코올은 메탄올 또는 에탄올인 것을 특징으로 하며, 상기 물과 저급 알코올의 혼합물은 30 내지 90% 에탄올인 것을 특징으로 한다. In the preparation method, the lower alcohol of step 3) is methanol or ethanol, and the mixture of water and lower alcohol is 30 to 90% ethanol.
상기 제조 방법에 있어서, 단계 4)의 분리 방법은 원심분리 방법인 것을 특징으로 한다. In the above production method, the separation method of step 4) is characterized in that the centrifugation method.
상기 제조 방법에 있어서, 크로마토그래피는 DEAE-셀룰로오스 레진을 이용한 음이온 교환 크로마토그래피인 것을 특징으로 한다. 상기 활성분획은 0.1 내지 0.5 M NaCl을 이용하여 분획하는 것이 바람직하며, 0.2 내지 0.4 M NaCl의 농도로 분획되는 것이 더욱 바람직하며, 0.3 M NaCl의 농도로 분획되는 것이 가장 바람직하다.In the above production method, the chromatography is characterized in that the anion exchange chromatography using DEAE-cellulose resin. The active fraction is preferably fractionated using 0.1 to 0.5 M NaCl, more preferably fractionated to a concentration of 0.2 to 0.4 M NaCl, and most preferably fractionated to a concentration of 0.3 M NaCl.
상기 제조방법은 하기와 같다: 1) 건조한 아칠리아속 식물 시료를 열수 추출하는 단계; 2) 단계 1)의 아칠리아속 식물의 열수 추출물을 감압농축하는 단계; 3) 단계 2)의 감압농축물을 크로마토그래피 방법을 통해 활성 분획을 수득하는 단계. The preparation method is as follows: 1) extracting hot water from a dry acyl plant sample; 2) depressurizing the hydrothermal extract of the genus Acyl plant of step 1); 3) obtaining an active fraction of the vacuum concentrate of step 2) by chromatography.
상기 제조 방법에 있어서, 단계 1)의 아칠리아속 식물은 큰톱풀(Achilla ptarmica subsp . macrocephala var . angustifolia Heim), 큰톱풀[Achillea acuminata ( Lebeb .) Sch . Bio], 큰톱풀(Achillea acuminata Freyn), 톱풀(Achillea alpina L.), 붉은톱풀[Achillea alpina subsp . rhodoptarmica ( Nakai ) Kitam], 산톱풀[Achillea alpina var , discoidea ( Regal ) Kitam], 서양톱풀(Achillea millefolium L.), 털톱풀[Achillea millefolium var . setacea ( Waldst & Koch )], 큰톱풀(Achillea ptarmica L.), 큰톱풀[Achillea ptarmica var . acuminata (Ledeb.) Heim], 산톱풀(Achillea ptarmicoides Naxim.), 붉은톱풀(Achilla rhodoptarmica Nakai), 털톱풀(Achilla setacea Waldst & Kit), 톱풀(Achillea sibirica Ledet .), 및 산톱풀(Achillea sibirica Var . discoidea Regal)인 것을 특 징으로 한다. In the above production method, the genus Acyl plants of step 1) may be Achilla ptarmica subsp . macrocephala var . angustifolia Heim ), A chillea acuminata ( Lebeb .) Sch . Bio , Achillea acuminata Freyn ), Yarrow ( Achillea alpina L. ), Yarrow [A chillea alpina subsp . rhodoptarmica ( Nakai ) Kitam ], Yarrow [ Achillea alpina var , discoidea ( Regal ) Kitam ], Achillea millefolium L. ), yarrow [ Achillea millefolium var . setacea ( Waldst & Koch ) ], Yarrow ( Achillea ptarmica L. ), yarrow [ Achillea ptarmica var . acuminata (Ledeb.) Heim ], Achillea ptarmicoides Naxim .), Red yarrow ( Achilla rhodoptarmica Nakai ), yarrow ( Achilla setacea Waldst & Kit ), yarrow ( Achillea sibirica Ledet . ), And mountain yarrow ( Achillea) sibirica Var . discoidea Regal ).
상기 제조 방법에 있어서, 단계 3)의 크로마토그래피는 DEAE-셀룰로오스 레진을 이용한 음이온 교환 크로마토그래피인 것을 특징으로 한다. In the above production method, the chromatography of step 3) is characterized in that the anion exchange chromatography using DEAE-cellulose resin.
상기 제조 방법에 있어서, 단계 3)의 활성분획은 0.1 내지 0.5 M NaCl을 이용하여 분획하는 것이 바람직하며, 0.2 내지 0.4 M NaCl의 농도로 분획되는 것이 더욱 바람직하며, 0.3 M NaCl의 농도로 분획되는 것이 가장 바람직하다. In the preparation method, the active fraction of step 3) is preferably fractionated using 0.1 to 0.5 M NaCl, more preferably fractionated to a concentration of 0.2 to 0.4 M NaCl, fractionated to a concentration of 0.3 M NaCl Most preferred.
이하, 본 발명을 실시예, 비교예, 실험예 및 제제예에 의하여 상세히 설명한다.Hereinafter, the present invention will be described in detail by Examples, Comparative Examples, Experimental Examples, and Formulation Examples.
단, 하기 실시예, 비교예, 실험예 및 제제예는 본 발명을 구체적으로 예시하는 것이며, 본 발명의 내용이 실시예, 실험예 및 제제예에 의해 한정되는 것은 아니다.However, the following Examples, Comparative Examples, Experimental Examples, and Formulation Examples specifically illustrate the present invention, and the content of the present invention is not limited to Examples, Experimental Examples, and Formulation Examples.
<실시예 1> 톱풀(Achillea alpina)의 주요 성분 분석Example 1 Analysis of Main Components of Yarrow ( Achillea alpina )
본 발명자들은 톱풀(일지호, Achillea alpina)의 주요성분을 분석하기 위하여 톱풀의 추출물을 표 1의 조건으로 한국 기초과학 지원 연구원에서 실시하였다.The inventors carried out the extract of the yarrow under the conditions of Table 1 in Korea Research Institute of Basic Science to analyze the main components of the yarrow (Ilji, Achillea alpina ).
그 결과, 푸코오스(fucose), 갈락토오스(glactose), 글루코오스(glucose) 및 만노오스(mannose) 등이 주요 성분으로 분석되었다(표 2).As a result, fucose, galactose, glucose and mannose were analyzed as major components (Table 2).
<실시예 2> 톱풀(Achillea alpina) 추출물(AA) 및 불용성 침전물(AAI) 제조Example 2 Preparation of Achillea alpina Extract (AA) and Insoluble Precipitate (AAI)
건조된 1 Kg의 톱풀 시료에 증류수 2 ℓ를 가한 후 60℃에서 7시간동한 2회 반복 추출한 후 회전 감압농축기로 추출액을 농축, 건조시켜 건조 분말 260 g을 수득하였으며 “AA"라 명명하였다. 이중 100 g의 건조 분말에 100% 메탄올 1 ℓ를 가하여 용해시킨 후, 10,000 rpm, 15분 동안 Soovall SS-34 원심분리기를 이용하여 메탄올에 용해된 분획(AAS)과 용해되지 않은 불용성 침전물을 분리하여 수득하였으며, 상기 불용성 침전물 44.3 g을 “AAI"라 명명하였다(도 1). 2 L of distilled water was added to the dried 1 Kg of yarrow sample, followed by repeated extraction for 7 hours at 60 ° C., and the extract was concentrated and dried using a rotary vacuum concentrator to obtain 260 g of dry powder, which was named “AA”. One liter of 100% methanol was dissolved in 100 g of the dry powder, and the fractions dissolved in methanol (AAS) and insoluble precipitates were separated using a Soovall SS-34 centrifuge for 10,000 rpm for 15 minutes. 44.3 g of this insoluble precipitate was named “AAI” (FIG. 1).
<실시예 3> 톱풀로부터의 항 B형 감염 바이러스 활성 성분 분리Example 3 Isolation of Anti-B Infectious Virus Active Ingredient from Yarrow
실시예 2에서 제조한 불용성 침전물(AAI)은 음이온 교환 크로마토그래피 레진(anion exchange chromatography resin)인 DEAE-셀룰로오스(celulose)에 충전한 후 증류수로 충분히 세척한 다음 0.1 M NaCl, 0.3 M NaCl, 0.5 M NaCl, 마지막으로 1 N NaOH로 용출시켜 이온 세기에 따른 활성분획을 수득하였다. The insoluble precipitate (AAI) prepared in Example 2 was charged with DEAE-cellulose, anion exchange chromatography resin, and washed well with distilled water, followed by 0.1 M NaCl, 0.3 M NaCl, 0.5 M Elution with NaCl, finally 1 N NaOH to give an active fraction according to the ionic strength.
그 결과, 3개의 분획을 수득하였으며, 0.1 M NaCl를 이용하여 수득한 분획을 “AAI-1"이라 명명하였고, 0.3 M NaCl을 이용하여 수득한 분획을 “AAI-2"라 명명하였으며, 1 N NaOH을 이용하여 수득한 분획을 “AAI-3"이라 명명하였다(도 2).As a result, three fractions were obtained, the fraction obtained using 0.1 M NaCl was named “AAI-1”, and the fraction obtained using 0.3 M NaCl was named “AAI-2”, 1 N The fraction obtained using NaOH was named “AAI-3” (FIG. 2).
<실시예 4> 톱풀로부터의 항 B형 감염 바이러스 활성 분획(AAI-2)의 주요 성분 분석Example 4 Analysis of Major Components of Anti-B Infectious Virus Active Fraction (AAI-2) from Yarrow
톱풀로부터 분리한 항 B형 감염 바이러스 활성 분획(AAI-2)의 주요 성분은 실시예 1과 같은 방법으로 수행하였다.The main component of the anti-B-infected virus active fraction (AAI-2) isolated from the yarrow was carried out in the same manner as in Example 1.
그 결과, 만노오스, 갈락토오스 및 글루코오스와 같은 당으로 구성되어 있음을 확인하였다(도 3). 또한, 유기산 조성 측정 결과 옥살산(oxalic acid)이 주요 유기산임을 확인하였다(도 4).As a result, it was confirmed that it is composed of sugars such as mannose, galactose and glucose (Fig. 3). In addition, the organic acid composition measurement results confirmed that oxalic acid (oxalic acid) is the main organic acid (Fig. 4).
<실시예 5> 톱풀 추출물(AA)로부터의 항 B형 감염 바이러스 활성 분획(AAI-2)의 수득 함량 조사Example 5 Investigation of the Yield Content of the Anti-B Infectious Virus Active Fraction (AAI-2) from Yarrow Extract (AA)
본 발명자들은 톱풀 추출물 그대로 건상식품에 이용하기 위하여, 에탄올을 이용하여 톱풀 추출물(AA)로부터 항 B형 감염 바이러스 활성 분획(AAI-2)의 수득시 함량을 조사하였다. The present inventors investigated the amount of the extract of the anti-B-infected virus active fraction (AAI-2) from the yarrow extract (AA) using ethanol in order to use the yarrow extract as a dry food.
본 발명자들은 톱풀 추출물(AA) 2 g으로 50%, 65% 및 80% 에탄올을 이용하여 항 B형 감염 바이러스 활성분획을 수득하였다(도 5). 상기 활성 분획을 실시예 4와 동일한 방법으로 분석한 결과, AAI-2와 동일한 성분임이 확인되었다. We obtained anti-type B virus active fraction using 50%, 65% and 80% ethanol with 2 g of yarrow extract (AA) (FIG. 5). The active fraction was analyzed in the same manner as in Example 4, and found to be the same component as AAI-2.
AA를 200 ㎖씩 가하여 50% 에탄올을 이용한 경우, 501 mg을 수득하였으며, 최종적으로 24 mg의 AAI-2를 수득하였다. 65% 에탄올의 경우, 522 mg을 수득하였으며, 최종적으로 43 mg의 AAI-2를 수득하였다. 80% 에탄올의 경우, 547 mg을 수득하였으며, 최종적으로 67 mg의 AAI-2를 수득하였다(도 5). 수득 방법으로는 음이온 교환 크로마토그래피 레진인 DEAE-Cellulose를 이용하여 0.1M NaCl, 0.3 M NaCl(AAI-2)로 용출시켜 이온 세기에 따라 활성분획을 수득하였다. 그 결과, 80%의 에탄올을 이용할 때 수율이 가장 좋은 것을 확인하였으며, 수율 측정 결과는 하기의 표 3과 같다.200 mL of AA was added to give 501 mg when using 50% ethanol, and finally 24 mg of AAI-2 was obtained. For 65% ethanol, 522 mg were obtained, finally 43 mg of AAI-2. For 80% ethanol, 547 mg were obtained, finally 67 mg of AAI-2 (FIG. 5). As an obtaining method, an active fraction was obtained by eluting with 0.1 M NaCl and 0.3 M NaCl (AAI-2) using DEAE-Cellulose, an anion exchange chromatography resin. As a result, it was confirmed that the best yield when using 80% ethanol, the yield measurement results are shown in Table 3 below.
<< 실험예Experimental Example 1> 톱풀 추출물( 1> Yarrow Extract ( AAAA ), 이의 불용성 침전물(), Its insoluble precipitate ( AAIAAI ) 및 톱풀에서 분리한 항 B형 감염 바이러스 활성분획() And active fraction of anti-B infection virus isolated from yarrow AAIAAI -1, -One, AAIAAI -2, -2, AAIAAI -3)의 항 간염 -3) anti-hepatitis 바이bye 러스 활성 측정Russ activity measurement
본 발명의 아칠리아속 식물의 추출물(AA), 이의 불용성 침전물(AAI) 및 이로부터 분리된 활성분획(AAI-1, AAI-2, AAI-3)이 B형 간염 바이러스에 대한 항 간염 바이러스 활성에 미치는 영향을 조사하기 위하여, 인간 간 조직 유래의 동물세포에 농도별로 톱풀 추출물(AA), 이의 불용성 침전물(AAI) 및 이의 활성분획(AAI-2)을 처리한 후, e항원 생성 억제 효과를 살펴보았다.Anti-hepatitis Virus Activity against Hepatitis B Viruses of Extracts (AA), Insoluble Precipitates thereof (AAI) and Active Fractions (AAI-1, AAI-2, AAI-3) In order to investigate the effect on the animal cells derived from human liver tissue, treatment with yarrow extract (AA), its insoluble precipitate (AAI) and its active fraction (AAI-2) at different concentrations, I looked at it.
<1-1> 2.2.15. 세포의 배양<1-1> 2.2.15. Cell culture
상기 활성을 조사하기 위하여, 인간의 간 조직에서 유래된 HepG2 세포(human hepatoblastoma cell)에 B형 간염 바이러스의 유전자가 삽입되어 있어 B형 간염 바이러스의 e 항원(HBeAg)을 배지로 생산하는 2.2.15. 세포주(Keui Ueda et al ., Virology 169, 213-21, 1989)를 이용하였다. 2.2.15. 세포는 지름 10 cm 페트리디쉬에 4 ㎍/㎖ 겐타마이신(gentamicin, Sigma, USA)과 10% 열처리된 우태아 혈청(Fetal bovine serum, Gibco, USA)이 첨가된 MEM 배지(Gibco, USA)를 사용하여 37℃, 5% CO2 배양기에서 배양하였다. 상기 조건으로 증식시켜 세포 단층이 형성되면 3~4일 간격으로 트립신을 처리하여 계대하였다.In order to investigate the activity, the hep B2 gene (human hepatoblastoma cell) derived from human liver tissue is inserted into the gene of hepatitis B virus 2.2.15 to produce the e antigen (HBeAg) of hepatitis B virus as a medium. . Cell line (Keui Ueda et al ., Virology 169, 213-21, 1989). 2.2.15. Cells were treated with MEM medium (Gibco, USA) supplemented with 4 μg / ml gentamicin (gentamicin, Sigma, USA) and 10% heat treated fetal bovine serum (Gibco, USA) in a 10 cm diameter petri dish. Incubated in a 37%, 5% CO2 incubator. When the cell monolayer was formed by proliferation under the above conditions, it was passaged by trypsin treatment at intervals of 3 to 4 days.
<1-2> B형 간염 바이러스 e 항원의 생성 저해 효과 측정<1-2> Measurement of the inhibitory effect of hepatitis B virus e antigen production
B형 간염 바이러스 e 항원의 생성 저해 효과는 B형 간염 항원 진단용 시약(Enzygnost HBeAg monoclonai, Behring, Germany)을 이용하여 효소면역 측정법을 실시하였다. 상기 실험예 1-1에서 배양된 2.2.15 세포를 24-웰 플레이트에서 웰당 2 × 104개의 농도로 FBS가 포함되지 않은 MEM 배지 배양액 100 ㎕와 함께 분주하였고 37℃, 5% CO2 배양기에서 24시간 동안 배양한 농도별로 톱풀 추출물(AA), 이의 불용성 침전물(AAI) 및 이의 활성분획(AAI-1, AAI-2, AAI-3)을 1.25, 2.5, 5.0 및 10.0 ㎍/㎖ 농도로 처리하였다. 톱풀 추출물(AA), 이의 불용성 침전물(AAI) 및 이의 활성분획(AAI-1, AAI-2, AAI-3)을 처리한지 48시간이 지난 다음 배양액만을 취하고 이 배양액을 1,500 rpm으로 5분 동안 원심분리하여 세포 분리물을 제거하였다. 이 때 얻은 상층 배양액만을 B형 간염 항원(HBeAg)에 대한 모노클로날 항체(HBeAb)가 도말되어 있는 진단시약 플레이트에 100 ㎕로 분주한 다음 37℃ 배양기에 1시간 동안 방치하여 B형 간염 항원과의 2차 결합이 이루어지도록 하였다. 결합되지 않은 항체는 인산 완충용액으로 3회 세척하여 제거하였으며 퍼옥시다아제에 의해 발색반응을 일으키는 TMB(tetramethyl benzidine dihydrochloride) 기질이 포함된 용액을 100 ㎕로 분주하여 발색 반응을 유도하였다. 반응이 완료된 진단시약 플레이트는 450 nm에서의 흡광 정도를 측정하여 e 항원의 변화를 평가하였다.The inhibitory effect of the hepatitis B virus e antigen production was measured by enzyme immunoassay using a reagent for diagnosing hepatitis B antigen (Enzygnost HBeAg monoclonai, Behring, Germany). 2.2.15 cells cultured in Experimental Example 1-1 were dispensed with 100 μl of MEM medium without FBS at a concentration of 2 × 10 4 per well in a 24-well plate at 37 ° C. and 5% CO 2 incubator. Treatment with yarrow extract (AA), its insoluble precipitate (AAI) and its active fraction (AAI-1, AAI-2, AAI-3) at concentrations of 1.25, 2.5, 5.0 and 10.0 μg / ml It was. After 48 hours of treatment with the extract of AA, its insoluble precipitate (AAI) and its active fractions (AAI-1, AAI-2, AAI-3), only the culture medium was taken and the culture was centrifuged at 1,500 rpm for 5 minutes. Isolation removes cell isolates. Only the supernatant obtained at this time was dispensed in 100 μl onto a diagnostic reagent plate coated with monoclonal antibody (HBeAb) against hepatitis B antigen (HBeAg), and left in a 37 ° C. incubator for 1 hour. The secondary bond of was made. Unbound antibody was washed three times with phosphate buffer, and 100 μl of a solution containing tetramethyl benzidine dihydrochloride (TMB) substrate, which was developed by peroxidase, was used to induce a color reaction. The diagnostic reagent plate was completed to evaluate the change of e antigen by measuring the degree of absorption at 450 nm.
그 결과, 톱풀 추출물(AA) 및 이의 불용성 침전물(AAI)은 모두 0.1 ㎍/㎖의 농도만으로도 세포 외부로 분비되는 e 항원의 생성을 급격히 저하시킴으로써 항간염 바이러스 활성을 나타냄을 알 수 있다(도 6). As a result, it can be seen that both the extract of the yarrow (AA) and its insoluble precipitate (AAI) exhibited anti-hepatitis virus activity by rapidly lowering the production of e antigen secreted outside the cells even at a concentration of 0.1 μg / ml (FIG. 6). ).
또한 본 발명의 활성 분획(AAI-1, AAI-2 및 AAI-3)의 경우, AAI-2 및 AAI-3 활성 분획이 효과적으로 항간염 바이러스 활성을 나타내었으며, 이 중 AAI-2 활성 분획이 표준물질과 동일한 간염 항원 감소능력을 보임을 확인하였다(도 7). In addition, in the active fractions of the present invention (AAI-1, AAI-2 and AAI-3), the AAI-2 and AAI-3 active fractions effectively showed anti-hepatitis virus activity, of which AAI-2 active fractions were the standard. It was confirmed that the same hepatitis antigen reduction ability as the material (Fig. 7).
본 발명자들은 HepG2 2.2.15 세포에서 e-항원 생성을 50% 방해하는 약물 농도(IC50)를 결정하여 표 4에 나타내었다.We determined the drug concentration (IC 50 ) that inhibits e-antigen production by 50% in HepG2 2.2.15 cells and is shown in Table 4.
<< 실험예Experimental Example 2> 톱풀 추출물( 2> yarrow extract ( AAAA ), 불용성 침전물(), Insoluble precipitate ( AAIAAI ) 및 이의 활성분획() And its active fraction ( AAIAAI -2)의 세포 독성 검사-2) cytotoxicity test
상기한 실시예로부터 분리된 추출물(AA), 불용성 침전물(AAI) 및 이의 활성 분획(AAI-2)의 활성을 검증하여 세포내 미치는 독성을 확인하기 위하여 공지의 방법(Korba, B, E, et al ., 19, 55-70, 1992)을 이용하여 세포 독성을 하기와 같이 조사하였다. Known methods (Korba, B, E, et ) to verify the toxicity of the extract (AA), insoluble precipitate (AAI) and its active fraction (AAI-2) isolated from the above-described examples to determine the toxicity in the cells al . , 19, 55-70, 1992), the cytotoxicity was investigated as follows.
24-웰 플레이트에 웰당 2 X 104개의 세포를 100 ㎕ 부피로 첨가하고 37℃ 배양기에서 24시간 동안 배양한 다음 여러 농도의 아칠리아 추출물(AA), 불용성 추출물(AAI) 및 이의 활성 분획(AAI-2)를 3일 동안 세포주에 처리하였다. 배양액을 제거하고 20 ㎕의 염색 용액[테트라졸리움 화합물(tetrazolium compound), 염(inner salt) 및 페나진에톨설페이트(phenazine ethosulfate)]을 분주하고 1시간 동안 배양기에서 반응시켰다. 이후 인산 완충용액으로 2회 세척하여 여분의 염색 용액을 제거하고 20 ㎕의 정착용액[50% 에탄올, 1% 차가운 아세트산(glacial acetic acid)]을 가하여 30분 동안 교반시켰다. 510 nm에서의 흡광도를 스펙트로포토메터로 측정하였며 추출물이 첨가되지 않은 음성 대조군 세포의 흡광도와 비교하여 50%의 흡광도 감소를 유발하는 추출물의 농도를 CC50(50% 세포독성 농도 : cytotoxic concentration)으로 결정하였으며, 그 결과를 하기 표 5에 나타내었다.100 μl volume of 2 × 10 4 cells per well was added to a 24-well plate and incubated for 24 hours in a 37 ° C. incubator, followed by various concentrations of alicia extract (AA), insoluble extract (AAI) and its active fraction (AAI). -2) were treated with the cell line for 3 days. The culture was removed and 20 μl of staining solution (tetrazolium compound, inner salt and phenazine ethosulfate) was dispensed and reacted in the incubator for 1 hour. After washing twice with phosphate buffer to remove the extra dye solution, 20 μl of fixation solution [50% ethanol, 1% cold acetic acid] was added and stirred for 30 minutes. The absorbance at 510 nm was measured with spectrophotometer and the concentration of the extract, which caused 50% decrease in absorbance compared to the absorbance of the negative control cells without the extract, was determined by CC 50 (50% cytotoxic concentration). It was determined as, and the results are shown in Table 5.
<< 실험예Experimental Example 3> 톱풀 추출물( 3> yarrow extract ( AAAA ), 톱풀의 불용성 침전물(), Insoluble precipitate of yarrow ( AAIAAI ) 및 활성분획() And active fraction ( AAIAAI -2)의 경구투여 급성 독성실험-2) Oral administration of acute toxicity test
본 발명자들은 톱풀 추출물(AA), 톱풀의 불용성 침전물(AAI) 및 활성분획(AAI-2)의 급성 독성을 알아보기 위하여 하기와 같은 실험을 수행하였다. 6주령의 특정병원부재(SPF) SD계 랫트를 사용하여 급성독성실험을 실시하였다. 톱풀 추출물(AA), 톱풀의 불용성 침전물(AAI) 및 활성분획(AAI-2)은 각각 0.5% 메틸셀룰로오스 용액에 현탁하여 5 g/kg/15 ㎖의 용량으로 단회 경구 투여하였다. 실험물질 투여 후 동물의 폐사 여부, 임상 증상, 체중 변화를 관찰하여 혈액학적 검사와 혈액 생화학적 검사를 실시하였으며, 부검하여 육안으로 복강장기와 흉강장기의 이상 여부를 관찰하였다. The present inventors conducted the following experiments to determine the acute toxicity of the extract of AA, the insoluble precipitate (AAI) and the active fraction (AAI-2) of the yarrow. Acute toxicity test was performed using 6-week-old SPF SD rats. Yarrow extract (AA), insoluble precipitate of yarrow (AAI) and active fraction (AAI-2) were each suspended orally administered in 0.5% methylcellulose solution at a dose of 5 g / kg / 15 ml. Hematology and blood biochemical tests were performed by observing the mortality, clinical symptoms, and weight changes of the animals after the administration of the test substance.
실험 결과, 실험물질을 투여한 모든 동물에서 특기할 만한 임상증상이나 폐사된 동물은 없었으며, 체중변화, 혈액검사, 혈액생화학검사, 부검소견 등에서도 독성 변화는 관찰되지 않았다. As a result, no significant clinical symptoms or dead animals were noted in all animals treated with the test substance, and no toxic changes were observed in weight changes, blood tests, blood biochemistry tests, and autopsy findings.
그 결과, 랫트에서 5 g/kg까지 독성 변화를 나타내지 않으며, 경구 투여 최소 치사량 (LD50)은 5 g/kg 이상인 안전한 물질로 판명되었다. As a result, the rats showed no toxicity change up to 5 g / kg, and the minimum lethal dose (LD 50 ) for oral administration was found to be a safe substance of 5 g / kg or more.
하기에 본 발명의 조성물을 위한 제제예를 예시한다.Examples of preparations for the compositions of the present invention are illustrated below.
<< 제제예Formulation example 1> : 약학적 제제의 제조 1>: Preparation of pharmaceutical preparation
1. 산제의 제조1. Preparation of powder
톱풀 추출물(AA), 톱풀의 불용성 침전물(AAI) Yarrow Extract (AA), insoluble precipitate of Yarrow (AAI)
또는 그의 활성분획(AAI-2) 2 gOr 2 g of its active fraction (AAI-2)
유당 1 g1 g lactose
상기의 성분을 혼합하고 기밀포에 충진하여 산제를 제조하였다.The above ingredients were mixed and filled in airtight cloth to prepare a powder.
2. 정제의 제조2. Preparation of Tablets
톱풀 추출물(AA), 톱풀의 불용성 침전물(AAI) Yarrow Extract (AA), insoluble precipitate of Yarrow (AAI)
또는 그의 활성분획(AAI-2) 100 ㎎Or 100 mg of active fraction thereof (AAI-2)
옥수수전분 100 ㎎
유 당 100 ㎎
스테아린산 마그네슘 2 ㎎2 mg magnesium stearate
상기의 성분을 혼합한 후, 통상의 정제의 제조방법에 따라서 타정하여 정제를 제조하였다.After mixing the above components, tablets were prepared by tableting according to a conventional method for producing tablets.
3. 캡슐제의 제조3. Preparation of Capsule
톱풀 추출물(AA), 톱풀의 불용성 침전물(AAI) Yarrow Extract (AA), insoluble precipitate of Yarrow (AAI)
또는 그의 활성분획(AAI-2) 100 ㎎Or 100 mg of active fraction thereof (AAI-2)
옥수수전분 100 ㎎
유 당 100 ㎎
스테아린산 마그네슘 2 ㎎2 mg magnesium stearate
상기의 성분을 혼합한 후, 통상의 캡슐제의 제조방법에 따라서 젤라틴 캡슐에 충전하여 캡슐제를 제조하였다.After mixing the above components, the capsule was prepared by filling in gelatin capsules according to the conventional method for producing a capsule.
4. 환의 제조4. Manufacture of rings
톱풀 추출물(AA), 톱풀의 불용성 침전물(AAI) Yarrow Extract (AA), insoluble precipitate of Yarrow (AAI)
또는 그의 활성분획(AAI-2) 1 gOr 1 g of its active fraction (AAI-2)
유당 1.5 gLactose 1.5 g
글리세린 1 g1 g of glycerin
자일리톨 0.5 gXylitol 0.5 g
상기의 성분을 혼합한 후, 통상의 방법에 따라 1환 당 4 g이 되도록 제조하였다.After mixing the above components, it was prepared to be 4 g per ring in a conventional manner.
5. 과립의 제조5. Preparation of Granules
톱풀 추출물(AA), 톱풀의 불용성 침전물(AAI) Yarrow Extract (AA), insoluble precipitate of Yarrow (AAI)
또는 그의 활성분획(AAI-2) 150 ㎎Or 150 mg of its active fraction (AAI-2)
대두추출물 50 ㎎Soy extract 50 mg
포도당 200 ㎎Glucose 200 mg
전분 600 ㎎Starch 600 mg
상기의 성분을 혼합한 후, 30% 에탄올 100 ㎎을 첨가하여 섭씨 60℃에서 건조하여 과립을 형성한 후 포에 충진하였다.After mixing the above components, 100 mg of 30% ethanol was added and dried at 60 ° C. to form granules, which were then filled into fabrics.
<< 제제예Formulation example 2> : 식품의 제조 2>: Manufacture of food
본 발명의 톱풀 추출물(AA), 톱풀의 불용성 침전물(AAI) 또는 그의 활성분획(AAI-2)을 포함하는 식품들을 다음과 같이 제조하였다.Food products containing the extract of the present invention (AA), insoluble precipitate (AAI) of the yarrow or the active fraction thereof (AAI-2) was prepared as follows.
1. 조리용 양념의 제조1. Preparation of Cooking Seasonings
본 발명의 톱풀 추출물(AA), 톱풀의 불용성 침전물(AAI) 또는 그의 활성분획(AAI-2)을 20~95 중량부로 건강 증진용 조리용 양념을 제조하였다.20 to 95 parts by weight of the extract of the present invention (AA), insoluble precipitate (AAI) of the yarrow or its active fraction (AAI-2) was prepared for cooking spices for health promotion.
2. 토마토 케찹 및 소스의 제조2. Preparation of Tomato Ketchup and Sauce
본 발명의 톱풀 추출물(AA), 톱풀의 불용성 침전물(AAI) 또는 그의 활성분획(AAI-2) 0.2~1.0 중량부를 토마토 케찹 또는 소스에 첨가하여 건강 증진용 토마토 케찹 또는 소스를 제조하였다.Health promotion tomato ketchup or sauce was prepared by adding 0.2-1.0 parts by weight of the extract of the yarrow extract (AA), insoluble precipitate of the yarrow (AAI) or its active fraction (AAI-2) to tomato ketchup or sauce.
3. 밀가루 식품의 제조3. Manufacturing of Flour Foods
본 발명의 톱풀 추출물(AA), 톱풀의 불용성 침전물(AAI) 또는 그의 활성분획(AAI-2) 0.5~5.0 중량부를 밀가루에 첨가하고, 이 혼합물을 이용하여 빵, 케이크, 쿠키, 크래커 및 면류를 제조하여 건강 증진용 식품을 제조하였다.0.5 to 5.0 parts by weight of the yarrow extract (AA) of the present invention, an insoluble precipitate of yarrow (AAI) or an active fraction thereof (AAI-2) is added to the flour, and bread, cake, cookies, crackers and noodles are prepared using this mixture. To prepare a health promoting food.
4. 스프 및 육즙(gravies)의 제조4. Preparation of soups and gravy
본 발명의 톱풀 추출물(AA), 톱풀의 불용성 침전물(AAI) 또는 그의 활성분획(AAI-2) 0.1~5.0 중량부를 스프 및 육즙에 첨가하여 건강 증진용 육가공 제품, 면류의 수프 및 육즙을 제조하였다.0.1 to 5.0 parts by weight of yarrow extract (AA), insoluble precipitate of yarrow (AAI) or active fraction thereof (AAI-2) of the present invention was added to soups and broth to prepare meat products for health promotion, soups and broths of noodles. .
5. 그라운드 비프(ground beef)의 제조5. Preparation of Ground Beef
본 발명의 톱풀 추출물(AA), 톱풀의 불용성 침전물(AAI) 또는 그의 활성분획(AAI-2)물 10 중량부를 그라운드 비프에 첨가하여 건강 증진용 그라운드 비프를 제조하였다.10 parts by weight of the yarrow extract (AA), insoluble precipitate (AAI) of the yarrow or the active fraction (AAI-2) of the present invention was added to the ground beef to prepare a ground beef for health promotion.
6. 유제품(dairy products)의 제조6. Manufacture of Dairy Products
본 발명의 톱풀 추출물(AA), 톱풀의 불용성 침전물(AAI) 또는 그의 활성분획(AAI-2) 5~10 중량부를 우유에 첨가하고, 상기 우유를 이용하여 버터 및 아이스크림과 같은 다양한 유제품을 제조하였다.5 to 10 parts by weight of the extract of the present invention (AA), insoluble precipitate of yarrow (AAI) or its active fraction (AAI-2) was added to milk, and various dairy products such as butter and ice cream were prepared using the milk. .
7. 선식의 제조7. Manufacture of wire
현미, 보리, 찹쌀, 율무를 공지의 방법으로 알파화시켜 건조시킨 것을 배전한 후 분쇄기로 입도 60 메쉬의 분말로 제조하였다.Brown rice, barley, glutinous rice, and yulmu were alphad by a known method, and then dried and roasted to prepare a powder having a particle size of 60 mesh.
검정콩, 검정깨, 들깨도 공지의 방법으로 쪄서 건조시킨 것을 배전한 후 분쇄기로 입도 60 메쉬의 분말로 제조하였다.Black beans, black sesame seeds, and perilla were also steamed and dried by a known method, and then ground to a powder having a particle size of 60 mesh.
본 발명의 톱풀 추출물(AA), 톱풀의 불용성 침전물(AAI) 또는 그의 활성분획(AAI-2)을 진공 농축기에서 감압농축하고, 분무, 열풍건조기로 건조하여 얻은 건조물을 분쇄기로 입도 60 메쉬로 분쇄하여 건조분말을 얻었다.The yarrow extract (AA) of the present invention, the insoluble precipitate (AAI) of the yarrow or its active fraction (AAI-2) was concentrated under reduced pressure in a vacuum concentrator, and the dried product obtained by drying with a spray or a hot air dryer is pulverized to a particle size of 60 mesh. To obtain a dry powder.
상기에서 제조한 곡물류, 종실류 및 톱풀 추출물(AA), 톱풀의 불용성 침전물(AAI) 또는 그의 활성분획(AAI-2)의 건조분말을 다음의 비율로 배합하여 제조하였다.Cereals, seeds and yarrow extract (AA), insoluble precipitate (AAI) of yarrow or dry powder of active fraction (AAI-2) prepared above were formulated in the following ratio.
곡물류(현미 30 중량부, 율무 15 중량부, 보리 20 중량부),Cereals (30 parts by weight brown rice, 15 parts by weight brittle, 20 parts by weight of barley),
종실류(들깨 7 중량부, 검정콩 8 중량부, 검정깨 7 중량부),Seeds (7 parts by weight perilla, 8 parts by weight black beans, 7 parts by weight black sesame seeds),
톱풀 추출물(AA), 톱풀의 불용성 침전물(AAI) 또는 그의 활성분획(AAI-2)의 건조분말(3 중량부),Dry powder (3 parts by weight) of yarrow extract (AA), insoluble precipitate of yarrow (AAI) or active fraction thereof (AAI-2),
영지(0.5 중량부),Ganoderma lucidum (0.5 parts by weight),
지황(0.5 중량부)Foxglove (0.5 part by weight)
<< 제제예Formulation example 3> : 음료의 제조 3>: Manufacture of beverage
1. 탄산음료의 제조1. Preparation of carbonated drinks
설탕 5~10%, 구연산 0.05~0.3%, 카라멜 0.005~0.02%, 비타민 C 0.1~1%의 첨가물을 혼합하고, 여기에 79~94%의 정제수를 섞어서 시럽을 만들고, 상기 시럽을 85~98℃에서 20~180초간 살균하여 냉각수와 1:4의 비율로 혼합한 다음 탄산가스를 0.5~0.82%를 주입하여 본 발명의 톱풀 추출물(AA), 톱풀의 불용성 침전물(AAI) 또는 그의 활성분획(AAI-2)을 함유하는 탄산음료를 제조하였다.5-10% of sugar, 0.05-0.3% citric acid, 0.005-0.02% caramel, 0.1-1% of vitamin C are mixed, and 79-94% purified water is mixed to make syrup, and the syrup is 85-98 Sterilize at 20 ° C. for 180 seconds, mix with cooling water at a ratio of 1: 4, and then inject 0.5 to 0.82% of carbon dioxide gas to extract yarrow extract (AA), insoluble precipitate of yarrow (AAI), or an active fraction thereof. A carbonated beverage containing AAI-2) was prepared.
2. 건강음료의 제조2. Manufacture of health drinks
액상과당(0.5%), 올리고당(2%), 설탕(2%), 식염(0.5%), 물(75%)과 같은 부재료와 본 발명의 톱풀 추출물(AA), 톱풀의 불용성 침전물(AAI) 또는 그의 활성분획(AAI-2)을 균질하게 배합하여 순간 살균을 한 후 이를 유리병, 패트병 등 소포장 용기에 포장하여 건강음료를 제조하였다.Substances such as liquid fructose (0.5%), oligosaccharides (2%), sugars (2%), salts (0.5%), water (75%) and the extract of the present invention (AA), insoluble precipitates of yarrow (AAI) Alternatively, the active fraction (AAI-2) was homogeneously blended and instant sterilized, and then packaged in a small packaging container such as a glass bottle or a plastic bottle to prepare a health beverage.
3. 야채쥬스의 제조3. Preparation of Vegetable Juice
본 발명의 톱풀 추출물(AA), 톱풀의 불용성 침전물(AAI) 또는 그의 활성분획(AAI-2) 5 g을 토마토 또는 당근 쥬스 1,000 ㎖에 가하여 건강 증진용 야채쥬스를 제조하였다.Vegetable juice for health promotion was prepared by adding 5 g of yarrow extract (AA) of the present invention, insoluble precipitate of yarrow (AAI) or its active fraction (AAI-2) to 1,000 ml of tomato or carrot juice.
4. 과일쥬스의 제조4. Preparation of Fruit Juice
본 발명의 톱풀 추출물(AA), 톱풀의 불용성 침전물(AAI) 또는 그의 활성분획(AAI-2) 1 g을 사과 또는 포도 쥬스 1,000㎖ 에 가하여 건강 증진용 과일쥬스를 제조하였다.Health promotion fruit juice was prepared by adding 1 g of yarrow extract (AA) of the present invention, an insoluble precipitate of yarrow (AAI) or an active fraction thereof (AAI-2) to 1,000 ml of apple or grape juice.
본 발명의 톱풀의 추출물, 이의 불용성 침전물 및 활성 분획은 B형 간염 바이러스 e 항원의 생성을 저해하며 독성이 없으므로 B형 간염 예방 및 치료용 약학적 조성물로 유용하게 이용될 수 있다.The extract of the yarrow of the present invention, its insoluble precipitate and active fraction inhibits the production of hepatitis B virus e antigen and can be useful as a pharmaceutical composition for hepatitis B prevention and treatment because it is not toxic.
Claims (31)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR1020070012139A KR100891488B1 (en) | 2007-02-06 | 2007-02-06 | The pharmaceutical composition containing effective ingredient of Achillea for prevent and treat of hepatitis B virus |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR1020070012139A KR100891488B1 (en) | 2007-02-06 | 2007-02-06 | The pharmaceutical composition containing effective ingredient of Achillea for prevent and treat of hepatitis B virus |
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| KR20080073473A KR20080073473A (en) | 2008-08-11 |
| KR100891488B1 true KR100891488B1 (en) | 2009-04-01 |
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| CN106324120A (en) * | 2016-08-09 | 2017-01-11 | 西藏藏医学院 | Volatile component measuring method for Tibetan medicine heracleum millefolium diels |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| JP2004231986A (en) * | 2003-01-28 | 2004-08-19 | Ishifuku Metal Ind Co Ltd | Apparatus for manufacturing uniformly spherical metal and manufacturing method therefor |
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| JP2004231986A (en) * | 2003-01-28 | 2004-08-19 | Ishifuku Metal Ind Co Ltd | Apparatus for manufacturing uniformly spherical metal and manufacturing method therefor |
Non-Patent Citations (2)
| Title |
|---|
| Phythotherapy research 20(7), pp. 546-551, 2006 |
| 천연물화학연구법, 민음사, pp. 16-23, 1986 |
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