WO2015108323A1 - Procédé de préparation d'un extrait d'artemisia sp. ayant une teneur en substance dangereuse réduite pour traiter une maladie gastrique et intestinale - Google Patents

Procédé de préparation d'un extrait d'artemisia sp. ayant une teneur en substance dangereuse réduite pour traiter une maladie gastrique et intestinale Download PDF

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Publication number
WO2015108323A1
WO2015108323A1 PCT/KR2015/000360 KR2015000360W WO2015108323A1 WO 2015108323 A1 WO2015108323 A1 WO 2015108323A1 KR 2015000360 W KR2015000360 W KR 2015000360W WO 2015108323 A1 WO2015108323 A1 WO 2015108323A1
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WIPO (PCT)
Prior art keywords
leaf
activated carbon
extract
ethanol
benzopyrene
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PCT/KR2015/000360
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English (en)
Korean (ko)
Inventor
김순회
손미원
전준호
박형근
한상덕
최상진
차봉진
이전평
최나영
홍성민
조성열
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동아에스티 주식회사
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Publication of WO2015108323A1 publication Critical patent/WO2015108323A1/fr

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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/28Asteraceae or Compositae (Aster or Sunflower family), e.g. chamomile, feverfew, yarrow or echinacea
    • A61K36/282Artemisia, e.g. wormwood or sagebrush
    • AHUMAN NECESSITIES
    • A63SPORTS; GAMES; AMUSEMENTS
    • A63FCARD, BOARD, OR ROULETTE GAMES; INDOOR GAMES USING SMALL MOVING PLAYING BODIES; VIDEO GAMES; GAMES NOT OTHERWISE PROVIDED FOR
    • A63F9/00Games not otherwise provided for
    • A63F9/30Capturing games for grabbing or trapping objects, e.g. fishing games
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00Drugs for disorders of the alimentary tract or the digestive system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/04Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
    • AHUMAN NECESSITIES
    • A63SPORTS; GAMES; AMUSEMENTS
    • A63FCARD, BOARD, OR ROULETTE GAMES; INDOOR GAMES USING SMALL MOVING PLAYING BODIES; VIDEO GAMES; GAMES NOT OTHERWISE PROVIDED FOR
    • A63F9/00Games not otherwise provided for
    • A63F9/24Electric games; Games using electronic circuits not otherwise provided for
    • 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
    • AHUMAN NECESSITIES
    • A63SPORTS; GAMES; AMUSEMENTS
    • A63FCARD, BOARD, OR ROULETTE GAMES; INDOOR GAMES USING SMALL MOVING PLAYING BODIES; VIDEO GAMES; GAMES NOT OTHERWISE PROVIDED FOR
    • A63F2250/00Miscellaneous game characteristics
    • A63F2250/14Coin operated
    • A63F2250/142Coin operated with pay-out or rewarding with a prize

Definitions

  • the present invention relates to a method for preparing a leaf extract, which can maintain the efficacy of treating gastrointestinal diseases while reducing the content of benzopyrene, a harmful substance in leaf extract.
  • Benzo [a] pyrene is a yellow crystalline solid belonging to the group of polyaromatic hydrocarbons (PAHs), and since it is produced by incomplete combustion at temperatures between 300 and 600 ° C., there are a variety of pollutants.
  • PAHs polyaromatic hydrocarbons
  • Benzopyrene is more problematic due to its long retention period and its high toxicity.It is an endocrine barrier and carcinogen, which is included in the priority list for risk assessment of CODEX (International Food Standards Commission) and JECFA (FAOWHO Joint Food Additives Expert Committee). It has become a target material of global interest.
  • the International Cancer Institute (IARC) recently upgraded benzopyrene to Group 1 human carcinogen. In foods, there is a problem with benzopyrene. Recently, the detection of benzopyrene in edible oils such as olive oil has become a social problem in Korea.
  • the leaf extract is used as a gastritis remedy for gastric mucosa regeneration by promoting prostaglandin production, HSP, VEGF and EGF production, promoting mucus secretion and gastric mucosa, protecting gastric mucosa and promoting healing of damaged gastric cells.
  • Korea Patent Publication No. 10-1000951, Republic of Korea Patent Publication No. 2009-0088343 and the like is known to be extracted and manufactured using a solvent belonging to ICH Guideline Class 3, such as alcohol and isopropyl alcohol.
  • leaf extracts are enriched with raw leaf herbals, benzopyrene, which is a harmful substance among leaf extracts, has affinity for organic solvents such as ethanol and isopropyl alcohol, which are used for extracting active ingredients such as eufatlin and zodiacine. High in some contaminated herbal medicines Benzopyrene may be included as the leaf extract.
  • Benzopyrene which may be present in trace amounts in leaf extracts, is very low in daily intake, and the amount exposed to the human body is much smaller than when ingested with other Chinese medicines or foods. There is a potential for unsupported risk. Therefore, the removal of benzopyrene in the leaf extract is an important task to be accomplished by those skilled in the art.
  • Active carbon is a special carbon that is mainly activated by using coconut shell, wood, and coal as a raw material, and is a collection of amorphous carbon with fine pore size of micropore in the process of activation.
  • Raw materials for activated carbon can be roughly classified into vegetable, animal, mineral and industrial waste, and minerals can be classified into coal and petroleum.
  • vegetable raw materials are used for the production of powdered activated carbon, and charcoal, coconut shell, coal, and the like are used for producing granular activated carbon.
  • Adsorption theory of activated carbon refers to a phenomenon in which certain components of gas or liquid are concentrated at the solid-liquid, gas-liquid, and liquid-liquid interface. Adsorption is usually classified into physical adsorption and chemical adsorption according to the type of adsorption. The force that dominates the physical adsorption is the van der Waals force, and the force that dominates the chemical adsorption is the chemical bonding force such as ionic bond or covalent bond. In the case of physical adsorption, solutes adhere to the adsorbent surface when the attraction of molecules between the solute and the adsorbent is greater than the attraction between the solute and the solvent.
  • the present invention overcomes the shortcomings of the conventional manufacturing method in which the benzopyrene derived from the crude drug is converted to the extract during the preparation of the lobar extract, and selectively maintains only the content of the harmful substance benzopyrene while maintaining the contents of the active ingredients eupatillin and zodiacine. It is an object of the present invention to provide a method for producing a leaf extract, which shows a gastrointestinal disease treatment effect equivalent to that of the extract when it is not treated with activated carbon.
  • the present invention relates to a method for producing a leafy leaf extract for treating gastrointestinal diseases in which the leaflet leaf extract of leaflet leaves with ethanol or propanol is reduced in the amount of harmful substances using activated carbon.
  • the leaf extract according to the present invention should have the following characteristics.
  • the present invention uses activated carbon to reduce the content of benzopyrene derived from the leaf of the leaf, leaf extracts treated with activated carbon with 0.1 to 20% (w / w) relative to the weight of leaf of the leaf, while significantly reducing the content of benzopyrene, eupatini, There is no significant change in the content of postural osdine, which shows the effect of treating the gastrointestinal diseases of the leaf extracts of the same level as the untreated activated carbon.
  • the content of benzopyrene as a harmful substance is reduced by about 99% (w / w) so that almost no benzopyrene remains in the leaf extract, Compared with unactivated charcoal, eufattylin and postiosidine were slightly decreased, but the gastrointestinal disease treatment effect was found to be equivalent.
  • leaf extract using 30 to 100% (w / w) activated carbon compared to the weight of leaf leaves can remove all of the harmful benzopyrene, but the active ingredient eupatillin, postiosidine also shows a large content change in the present invention Excluded from the category of.
  • the present invention is characterized by using 0.1 to 20% (w / w) activated carbon relative to the weight of the leaf of the leaf, preferably from 0.1 to 5% (w / w) activated carbon.
  • Leaf leaf in the present invention can be extracted with ethanol or propanol, ethanol is not changed in the benzopyrene content reduction ability in the range of 70 ⁇ 100% (v / v) concentration when activated carbon filtration process, 95% (v / v) Ethanol is preferred.
  • Propanol also uses 1-propanol or 2-propanol with a 100% (v / v) concentration.
  • the present invention provides a method for reducing the benzopyrene content by using 0.1 ⁇ 20% (w / w) activated carbon compared to the weight of the leaf of the leaf leaf extract ethanol or propanol.
  • the process of reducing benzopyrene in the leaf extract can be treated during the extraction of the leaf of the leaf, the treatment before the extraction of the leaf of the leaf, or the leaf of the leaf extract can be treated after re-dissolution.
  • the step of processing during extraction of the leaf of the leaf is to extract the leaf of the leaf with a solvent to remove the benzopyrene by circulating filtration using a column filled with activated carbon, the process of extracting the leaf of the leaf before the leaf is leaf After filtration and solvent extraction, the column packed with activated carbon was filtered to remove benzopyrene, and the treatment process after concentration and re-dissolution of the leaf extract was carried out by solvent extraction of the leaf of the leaf, and the extract obtained by concentration under reduced pressure was extracted. It is a method of removing benzopyrene by circulating filtration using a column filled with activated carbon after redissolution with a solvent.
  • the benzopyrene reduction rate and the amount of eupatylin and oseosidine, which are active ingredients of the leaves, can be similarly obtained in all solvents.
  • the present invention overcomes the shortcomings of the conventional manufacturing method in which the benzopyrene derived from the original drug is transferred to the extract during the preparation of the leaf extract, the benzopyrene content is reduced and the content of the active substance is maintained to provide a method for producing the leaf extract having medicinal effects .
  • 1 is a graph showing the content of benzopyrene, eupatillin, and postiosidine compared to untreated activated carbon of the leaf extract.
  • Figure 2 is a graph showing the inhibition of gastric lesions of the leaf extract according to the activated carbon filter process compared to the activated carbon untreated leaf extract.
  • the following examples extract the leaflets with 70% (v / v), 80% (v / v), 85 (v / v), 90% (v / v) and 100% (v / v) ethanol.
  • active carbon 5% (w / w) compared to the crude drug as in Example 3 to prepare a leaf extract according to the present invention.
  • 100 g of fine leaf leaves were immersed in 800 ml of 90% (v / v) ethanol at room temperature for 20 hours, and circulated by filtration using a column filled with 5 g of activated carbon, and then the residue was again 800 ml of 90% (v / v) ethanol. After 4 hours of cooling, the column filled with 5 g of activated carbon was filtered through a column. The combined filtrates were concentrated under reduced pressure to obtain about 5 g of soft extract.
  • the following example extracts leaflets with 100% (v / v) 1-propanol and 100% (v / v) 2-propanol instead of extractant ethanol and activated carbon 5% (w) / w) to prepare a leaf extract according to the present invention.
  • 100 g of fine leaf leaves were immersed in 800 ml of 95% (v / v) ethanol at room temperature for 20 hours, and circulated by using a column filled with 100 g of activated carbon, and then the residue was again 800 ml of 95% (v / v) ethanol. After 4 hours of cooling and circulating filtration using a column filled with 100g of activated carbon. The combined filtrates were concentrated under reduced pressure to obtain about 5 g of soft extract.
  • 100 g of fine leaf leaves were immersed in 800 ml of 95% (v / v) ethanol at room temperature for 20 hours, and circulated through a column filled with 30 g of activated carbon, and the residue was again filtered into 800 ml of 95% (v / v) ethanol. After 4 hours of cooling, the column was filled with 30 g of activated carbon and filtered through a column. The combined filtrates were concentrated under reduced pressure to obtain about 5 g of soft extract.
  • the larvae extract (Comparative Examples 1 to 3) using activated carbon 30 ⁇ 100% (w / w) compared to the original drug can remove all benzopyrene, but it is an active ingredient Tilin and postiosidine also showed large content changes.
  • Examples 1 to 5 according to the present invention can be seen that there is no significant change in the content of eupatillin, and postiosidine while showing a benzopyrene reduction effect.
  • Example 5 it can be seen that even if the amount of activated carbon compared to the original drug using 0.1% (w / w) benzopyrene is reduced by about 80% (w / w).
  • Comparative Examples 2 and 3 can remove all of the amount of benzopyrene, but the active ingredients, eupatilin, and postiosidine also showed a large content change, so that the effect of inhibiting gastric bleeding lesions was negligible
  • the present invention when using 0.1% (w / w) to 20% (w / w) of activated carbon compared to the original drug, while reducing the benzopyrene, a harmful substance compared to the activated carbon untreated group, the effect of inhibiting gastric bleeding lesions It can be seen that.
  • the activated carbon filtration process in the present invention does not have a difference between application time points.
  • Comparative evaluation was performed for each solvent. Examples 3 and 8 to 14 were compared among the examples extracted using the activated carbon filtration process. Comparative Example 8, which was not treated with activated carbon, was used as a control. Each soft extract was evaluated using high performance liquid chromatography (HPLC) and the results are shown in Table 4.

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  • Natural Medicines & Medicinal Plants (AREA)
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Abstract

La présente invention concerne un procédé de préparation d'un extrait d'Artemisia sp., extrait de feuilles d'Artemisia sp. avec de l'éthanol ou du propanol, pour traiter une maladie gastrique et intestinale, qui réduit une teneur en substance dangereuse en utilisant du charbon actif. Le procédé de préparation d'un extrait d'Artemisia sp. selon la présente invention utilise du charbon actif, de manière à réduire le benzo[a]pyrène dérivé d'un produit médicinal à base d'herbes brutes de manière à produire l'extrait d'Artemisia sp. avec une sécurité augmentée et sans changements de l'effet médicinal. Par conséquent, l'extrait d'Artemisia sp. préparé par le procédé de préparation selon la présente invention peut réduire efficacement le benzo[a]pyrène, qui est la substance dangereuse, tout en conservant un effet médicinal.
PCT/KR2015/000360 2014-01-15 2015-01-14 Procédé de préparation d'un extrait d'artemisia sp. ayant une teneur en substance dangereuse réduite pour traiter une maladie gastrique et intestinale WO2015108323A1 (fr)

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KR1020140005082A KR20150085330A (ko) 2014-01-15 2014-01-15 유해물질의 함량을 저감시킨 위장질환 치료용 애엽 추출물의 제조방법
KR10-2014-0005082 2014-01-15

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KR102414382B1 (ko) 2015-12-18 2022-06-30 대원제약주식회사 벤조피렌이 저감된 애엽 추출물의 제조방법
CN108786745A (zh) * 2018-06-08 2018-11-13 张守 一种基于艾杆活性炭的粉体材料及其用途
CN117160412B (zh) * 2023-10-08 2024-02-27 宁波绿之健药业有限公司 一种用于艾叶提取用的改性活性炭的制备方法和应用

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KR20060002639A (ko) * 2004-07-03 2006-01-09 동아제약주식회사 혈액응고 억제성분이 제거된 애엽 추출물, 이의 제조방법및 이를 유효성분으로 함유하는 약학적 조성물
KR20090080459A (ko) * 2008-01-21 2009-07-24 김경희 약초를 이용한 어,패류 양식수 또는 보관수 제조방법
KR20090088343A (ko) * 2008-02-14 2009-08-19 지엘팜텍 주식회사 고함량의 유파틸린을 함유하는 쑥 추출물

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KR20060002639A (ko) * 2004-07-03 2006-01-09 동아제약주식회사 혈액응고 억제성분이 제거된 애엽 추출물, 이의 제조방법및 이를 유효성분으로 함유하는 약학적 조성물
KR20090080459A (ko) * 2008-01-21 2009-07-24 김경희 약초를 이용한 어,패류 양식수 또는 보관수 제조방법
KR20090088343A (ko) * 2008-02-14 2009-08-19 지엘팜텍 주식회사 고함량의 유파틸린을 함유하는 쑥 추출물

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