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KR101703352B1 - Artemisia extract - Google Patents

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KR101703352B1
KR101703352B1 KR1020090001258A KR20090001258A KR101703352B1 KR 101703352 B1 KR101703352 B1 KR 101703352B1 KR 1020090001258 A KR1020090001258 A KR 1020090001258A KR 20090001258 A KR20090001258 A KR 20090001258A KR 101703352 B1 KR101703352 B1 KR 101703352B1
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butanol
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왕훈식
박준상
오진섭
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지엘팜텍주식회사
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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    • A61K36/28Asteraceae or Compositae (Aster or Sunflower family), e.g. chamomile, feverfew, yarrow or echinacea
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    • A61K2236/33Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
    • A61K2236/50Methods involving additional extraction steps
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Abstract

본 발명은 탄소수 4의 알코올류로 추출하여 얻은 애엽 추출물에 대한 것으로서, 기존 기술에 비해 별도의 제거 공정을 추가하지 않더라도 혈액응고억제 물질이 완전히 제거된 애엽 추출물에 대한 것이다.The present invention relates to a lobule extract obtained by extracting with alcohol having 4 carbon atoms and a lecithin extract in which blood coagulation inhibitor is completely removed even if a separate elimination step is not added as compared with the conventional art.

애엽(Artemisia), 애엽 추출물(Artemisia extract), 알코올(alcohol) Artemisia, Artemisia extract, alcohol,

Description

애엽 추출물{ARTEMISIA EXTRACT}{ARTEMISIA EXTRACT}

쑥(Artemisia mongolica, A. asiatica, A. princeps var. orientalis, A. argyi, A. montana 등)은 국화과에 속하는 다년생 약초로서 예로부터 강장보혈, 부인병, 설사치료제로 사용되어 왔으며 규명된 화학성분으로서 이소쿠마린, 쿠마린, 디테르펜락톤 등이 있으며 유파틸린, 자세오시딘 등의 플라보이노이드 성분 등도 확인되었다.대한약전외 한약(생약)규격집에서는 상기 쑥의 잎 및 어린줄기를 일컬어 애엽(艾葉, Artemisiae argyi Herb)이라 지칭하고 있다. 이 중 플라보노이드 성분인 유파틸린(eupatilin)은 항알러지 효과(일본 공개특허공보 소59-155314호)가 알려진 바 있으며 최근 국내에서 위장질환 치료제로서의 효용성에 대해서도 밝혀진 바 있다. (대한민국 특허등록 127777) 더불어, 또 다른 플라보노이드 성분인 자세오시딘(jaseocidin) 역시 동일한 위장질환 치료제로서 사용 가능함이 특허로 등록된 바 있다. (대한민국 특허등록 181751) Artemisia mongolica, A. asiatica, A. princeps var. Orientalis, A. argyi, A. montana, etc.) is a perennial herb belonging to Asteraceae and has been used as an agent for the treatment of gynecological diseases, gynecological diseases and diarrhea And the flavanoids such as yupatilin and oriental ostidine were also identified in the Korean Pharmacopoeia Specification of Chinese medicine (herbal medicine). Also, the leaves and young stems of the mugwort were also called "叶葉, Artemisiae argyi Herb). Among them, eupatilin, which is a flavonoid component, has been known to have an antiallergic effect (Japanese Patent Laid-Open Publication No. 59-155314), and its utility as a therapeutic agent for gastrointestinal diseases has recently been disclosed in Korea. (Korean Patent Registration No. 127777) In addition, another flavonoid component, jaseocidin, is also registered as a patent that can be used as a therapeutic agent for the same gastrointestinal diseases. (Korean Patent Registration No. 181751)

한편, 대한민국 특허등록 181751에서는, 쑥으로부터 정제한 유파틸린 또는 자세오시딘의 항위염 효과에 비해 쑥 추출물 자체의 항위염 효과가 더욱 뛰어나 해당 추출물 중 미지의 물질들이 항위염 효과를 상승시키는 것으로 추정 기술하고 있다.대한민국 특허공개 2006-0002639에서는, 쑥에 함유되어 있는 혈액응고억제 성분 즉, 쿠마린(coumarin)류 특히, 디쿠마롤(Dicoumarol) 성분이 추출 과정에서 포함된다고 적시하고 있다.On the other hand, Korean Patent Registration No. 181751 discloses that the antagonistic effect of mugwort extract itself is more excellent than the antitumor effect of refined mugwort-infused oil tilline or oriental osidine, Korean Patent Laid-Open Publication No. 2006-0002639 discloses that the blood coagulation inhibitory component contained in mugwort, that is, coumarin, especially Dicoumarol, is contained in the extraction process.

선행기술에 기술된 바와 같이 디쿠마롤은 소량의 투약으로도 혈소판 수를 급격히 감소시킬 수 있고 간독성도 보고된 바 있어 의학적 용도로 사용할지라도 매우 신중을 기해 투약되어야 하는 성분에 해당한다. 더욱이, 위염 또는 위궤양 환자는 위장 손상에 의한 위출혈이 동반되는 경우가 허다하므로 이 같은 성분은 반드시 제거되어야만 약효 증가를 더욱 기대할 수 있다 하겠다. 또한, 상기 선행기술에서는, 기존의 대한민국 특허등록 181751에 따른 알코올 또는 알코올 수용액 추출물에서는 이 성분의 제거가 용이하지 않음을 적시하고 있으며 이를 제거할 수 있는 방법으로서, 1) 애엽 잎을 알코올 또는 알코올 수용액으로 추출하는 단계(단계1), 2) 상기 단계1에서 얻어진 추출물에 알칼리 용액을 첨가하고 80℃에서 1시간 이상 반응시키는 단계(단계2), 3) 상기 단계2에서 얻어진 추출물에 산성 용액을 첨가하여 중화시키는 단계(단계3) 및 4) 상기 단계3에서 얻어진 추출물을 감압농축한 후 동결건조하는 단계(단계4)를 포함하는 제조방법을 제공하고 있다. 즉, 선행기술에 단계2 및 단계3의 알칼리 처리 및 이의 중화 과정을 포함시킴으로써 디쿠마롤 성분을 용이하게 제거할 수 있음을 알 수 있다.본 발명에서는 기존 추출법과 달리 추출 용매를 에탄올에서 탄소수 4(C4)의 알코올류로 치환할 경우, 별도의 추가 제거 공정을 거치지 않더라도, 혈액응고억제성분인 디쿠마롤이 포함되지 않는 것을 발견하여 본 발명을 완성하였다.As described in the prior art, decumarol is a component that can be used with great care even though it can be used for medical purposes because it can dramatically reduce the platelet count even with small doses and has reported hepatotoxicity. In addition, patients with gastritis or gastric ulcer are more likely to have gastrointestinal bleeding due to gastrointestinal damage. In the above-mentioned prior art, it is stated that the alcohol or alcohol aqueous solution extract according to the conventional Korean Patent Registration No. 181751 does not easily remove this component. As a method for removing this component, 1) (Step 1); 2) adding an alkali solution to the extract obtained in step 1 and reacting at 80 ° C for 1 hour or more (step 2); 3) adding an acidic solution to the extract obtained in step 2 (Step 3); and 4) lyophilizing the extract obtained in step 3 after concentration under reduced pressure (step 4). That is, it can be seen that the dicumarol component can be easily removed by including alkali treatment of steps 2 and 3 and its neutralization process in the prior art. Unlike the conventional extraction method, in the present invention, (C4), it does not contain decumarol, which is a blood coagulation inhibiting component, even without a separate additional removal step, thereby completing the present invention.

본 발명은 별도의 제거공정을 거치지 않더라도 혈액응고성분인 디쿠마롤이 포함되지 않는 애엽 추출물을 확보하는 것을 목적으로 한다.It is an object of the present invention to provide a lyocyte extract which does not contain a coagulant component, which is a blood coagulation component, even though a separate removal step is not performed.

본 발명은 애엽을 탄소수 4의 알코올류 예컨대, 2-부탄올(이소부탄올), 1-부탄올(n-부탄올), 2-메칠-1-프로판올(sec-부탄올) 등으로 추출, 농축한 애엽 추출물에 대한 것으로 추출, 농축 과정에서 혈액응고억제 물질 즉, 디쿠마롤을 제거하기 위한 별도의 공정을 포함시키지 않더라도 디쿠마롤을 함유하지 않는 것을 특징으로 한다.본 발명에 사용되는 애엽은 황해쑥(Artemisia argyi), 쑥(A. princeps var. orientalis, A. asiatica), 산쑥(A. montana), 참쑥(A. mongolica) 및 대한약전외 한약(생약)규격집에 정의된 동속식물을 포함한다. 본 발명에서 사용되는 탄소수 4의 알코올류는 2-부탄올, 1-부탄올, 2-메칠-1-프로판올을 포함한다.본 발명은, 애엽에 상기 탄소수 4의 알코올류를 가해 통상의 생약추출법 즉, 침지법, 환류법을 통해 추출하여 이를 적절한 방법으로 여과한 뒤 별도의 추가 공정 없이 바로 농축하여 애엽 추출물을 최종 확보한다.침지법을 사용하는 경우, 애엽에 상기 용매를 가해 충분한 시간 동안 침지하고 이를 적절한 방법으로 여과한 뒤 감압농축하여 추출물을 획득한다.The present invention relates to a method of extracting and extracting a leaf from an extract of a leaf, which is extracted and concentrated with an alcohol having 4 carbon atoms, such as 2-butanol (isobutanol), 1-butanol (n-butanol), 2-methyl- The present invention is characterized in that it does not contain decumaryl, even if it does not contain a blood coagulation inhibitor, that is, a separate process for removing the decumarol in the extraction and concentration process. The lobes used in the present invention are Artemisia A. montana, A. mongolica, and the Korean Pharmacopoeia (herbal medicines) Specification, for example, A. argini, A. argini, A. princeps var. orientalis, A. asiatica. The present invention relates to a method of extracting alcohol from a mixture of an alcohol having 4 carbon atoms and a conventional method for extracting medicines, that is, The leaching solution is immersed in the solution for a sufficient period of time after adding the solvent to the solution of the leaching solution, After appropriate filtration, the filtrate is concentrated under reduced pressure to obtain an extract.

본 발명을 통해 별도의 추가 제거공정을 포함하지 않더라도 혈액응고억제성 분이 포함되지 않는 애엽 추출물을 확보할 수 있다.Through the present invention, it is possible to secure a lyophilized extract which does not contain a blood coagulation inhibitor even if it does not include a separate additional removal step.

<실시예1>&Lt; Example 1 >

애엽 (Artemisia princeps Pamp. var. orientalis) 300g에 2-부탄올 2500mL을 가해 약 24시간 동안 침지추출하고 이를 80℃로 가열, 진공여과한다. 잔사에 2-부탄올 1300mL을 추가하여 약 24시간 동안 침지추출하고 동일 공정을 거쳐 여과한 뒤 이전 여과추출물과 합친다. 이를 원심분리여과하여 쑥 추출물 15.7g을 얻었다. (수득율 약 20:1)To 300 g of Artemisia princeps Pamp. Var. Orientalis, 2500 mL of 2-butanol is added, and the mixture is immersed for about 24 hours. The mixture is heated to 80 캜 and vacuum filtered. To the residue was added 1300 mL of 2-butanol, followed by immersion extraction for about 24 hours, filtering through the same process, and combining with the previous filtrate. This was centrifuged and filtered to obtain 15.7 g of Mugwort extract. (Yield about 20: 1)

<실시예2>&Lt; Example 2 >

애엽 (Artemisia princeps Pamp. var. orientalis) 300g에 1-부탄올 2500mL을 가해 약 24시간 동안 침지추출하고 이를 80℃로 가열, 진공여과한다. 잔사에 1-부탄올 1300mL을 추가하여 약 24시간 동안 침지추출하고 동일 공정을 거쳐 여과한 뒤 이전 여과추출물과 합친다. 이를 원심분리여과하여 쑥 추출물 15.5g을 얻었다. (수득율 약 20:1)To 300 g of Artemisia princeps Pamp. Var. Orientalis, 2500 mL of 1-butanol is added and the mixture is immersed for about 24 hours. The mixture is heated to 80 캜 and vacuum filtered. 1-butanol (1300 mL) was added to the residue, and the mixture was immersed for about 24 hours, filtered through the same process, and then combined with the previous filtrate. This was centrifuged and filtered to obtain 15.5 g of Mugwort extract. (Yield about 20: 1)

<실시예3>&Lt; Example 3 >

애엽 (Artemisia princeps Pamp. var. orientalis) 300g에 2-메칠-1-프로판올 2500mL을 가해 약 24시간 동안 침지추출하고 이를 80℃로 가열, 진공여과한다. 잔사에 2-메칠-1-프로판올 1300mL을 추가하여 약 24시간 동안 침지추출하고 동일 공정을 거쳐 여과한 뒤 이전 여과추출물과 합친다. 이를 원심분리여과하여 쑥 추출물 15.5g을 얻었다. (수득율 약 20:1)To 300 g of Artemisia princeps Pamp. Var. Orientalis, 2500 mL of 2-methyl-1-propanol is added, and the mixture is immersed and extracted for about 24 hours. To the residue was added 1300 mL of 2-methyl-1-propanol, followed by immersion extraction for about 24 hours, filtration through the same process, and combining with the previous filtrate. This was centrifuged and filtered to obtain 15.5 g of Mugwort extract. (Yield about 20: 1)

<실험예1> 추출용매에 따른 유파틸린, 자세오시딘 및 디쿠마롤 함량EXPERIMENTAL EXAMPLE 1 [0041] The contents of the milk tiller, the postural oocidine and the dicumarol

상기 실시예에 따른 추출물 중 약효발현 지표물질인 유파틸린 및 자세오시딘과 혈액응고억제 성분인 디쿠마롤의 함유량은 다음과 같다.Among the extracts according to the above examples, the content of the drug efficacy indicator oil substances, that is, the content of dipyrrhin, the positional osteidine and the blood coagulation inhibiting component, is as follows.

실시예
Example
성분함량Ingredient content
유파틸린Yupatiline 자세오시딘Posture osidine 디쿠마롤Dicumarol 실시예 1Example 1 1.95%1.95% 0.99%0.99% 비검출Non-detection 실시예 2Example 2 2.92%2.92% 1.48%1.48% 비검출Non-detection 실시예 3Example 3 0.60%0.60% 0.32%0.32% 비검출Non-detection

즉, 약효발현 성분으로 알려진 유파틸린 및 자세오시딘을 함유하면서도 혈액응고억제 성분인 디쿠마롤이 전혀 검출되지 않는 결과를 나타내었다.In other words, it was found that no dicumarol, which is a blood coagulation inhibiting component, was contained in the solution containing ephedrine and postural oocyte, which are known as active ingredients.

도 1은 디쿠마롤 표준품의 크로마토그램이다.Figure 1 is a chromatogram of a standard product of Dicumarol.

도 2는 실시예 1에 따른 애엽의 2-부탄올 추출물의 크로마토그램이다.2 is a chromatogram of the 2-butanol extract of the leaf of Example 1;

도 3는 실시예 2에 따른 애엽의 1-부탄올 추출물의 크로마토그램이다.3 is a chromatogram of the 1-butanol extract of the leaf of Example 2;

도 4는 실시예 3에 따른 애엽의 2-메틸-1-프로판올 추출물의 크로마토그램이다.4 is a chromatogram of the 2-methyl-1-propanol extract of the leaf of Example 3.

도 5는 도 1내지 4를 겹쳐서 확대한 크로마토그램이다.FIG. 5 is a chromatogram obtained by overlapping and enlarging FIGS. 1 to 4. FIG.

Claims (4)

삭제delete 삭제delete 삭제delete 2-부탄올, 1-부탄올 및 2-메칠-1-프로판올로 이루어지는 군으로부터 선택되는 탄소수 4의 알코올류로 애엽을 추출하는 공정; 및A step of extracting leaflets with an alcohol having 4 carbon atoms selected from the group consisting of 2-butanol, 1-butanol and 2-methyl-1-propanol; And 상기 추출물을 여과, 농축하는 공정을 포함하는 애엽 추출물의 제조방법으로서, 별도의 디쿠마롤 제거 공정을 포함하지 않는 것을 특징으로 하는 디쿠마롤 비함유 애엽 추출물의 제조방법.A method for producing a lyophilized extract, which comprises a step of filtering and concentrating the extract, wherein the lyocarol-free lyocyte extract is free from a step of removing a decumarole.
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