CN1310624A - 药物组合物和化妆品组合物的萃取方法 - Google Patents
药物组合物和化妆品组合物的萃取方法 Download PDFInfo
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/11—Pteridophyta or Filicophyta (ferns)
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/96—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
- A61K8/97—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from algae, fungi, lichens or plants; from derivatives thereof
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- A61K8/97—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from algae, fungi, lichens or plants; from derivatives thereof
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- A61K2236/30—Extraction of the material
- A61K2236/33—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
- A61K2236/331—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using water, e.g. cold water, infusion, tea, steam distillation or decoction
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Abstract
本发明涉及一种从植物材料中萃取化合物的方法,其中将植物材料的尺寸减小,然后用溶剂萃取。根据本发明,用液冷冻植物材料,然后在冷冻条件下减小植物材料的尺寸。根据两个重要的实施方案,植物材料来自银杏树,特别是新鲜的树叶,而水用作溶剂。本发明还涉及含有用本发明的方法制得的化合物作为活性组分的药物制剂和化妆品制剂。
Description
本发明涉及一种从植物材料中萃取化合物的方法，在这一方法中，将植物材料的尺寸减小，用溶剂进行萃取处理，然后从含有所述化合物的溶剂中分离不溶解的部分。
这类方法是十分古老的。其例子是茶叶的泡制和药酒的制备。在这两种情况下，通常从含有所述化合物的溶剂中分离不溶解的部分。例如用过滤或离心分离进行这一操作。
已知方法的缺点在于，或多或少的活性化合物留在分离后的不溶部分中。
本发明的一个目的是提供一种第一段中描述的方法，用这一方法可提高活性化合物的产率。
为此，该法的特征在于，用液化的气体将植物材料冷冻，并用溶剂萃取以前，在冷冻条件下将它的尺寸减小。
在这一方法中，使植物材料有效地疏松，从而保证有更高的产率百分数。液氮十分适用于这一目的，因为它是惰性的(无氧化性)和廉价的。
EP 0477968公开了一种通过在40-100℃下用丙酮水溶液、C1-C3链烷醇水溶液或无水甲醇处理树叶来制备银杏树萃取物的方法。在除去固体部分以后，用硫酸铵、甲乙酮处理这一溶液，然后用高级链烷醇萃取生成的萃取物。在几个另外的步骤以后，制得含有20％(重量)以上黄苷、2.5-4.4％(重量)银杏苦内酯A、B、C和J以及2.0-4.0％(重量)％白果内酯的萃取物。所述的萃取方法是很费力的。
EP 0431535公开了一种由银杏树叶制备萃取物的方法，它基本上与上述方法相当。此外，铅盐用于进一步的转化。由于这一原因，这一萃取方法也是很费力的，而且由于使用了铅化合物，对环境和人类健康都是有害的。
根据一重要的实施方案，植物材料选自银杏树和蛇足石杉的植物部分。
这样的植物材料可用本发明概述的方法很好地萃取，得到药物上高品质的溶液。可从银杏树的植物部分萃取出银杏苦内酯和类黄酮。可从蛇足石杉的植物部分分离出Huberazine。所有这些化合物都具有有意义的药物性质，
所使用的银杏树最优选的植物部分是新鲜的树叶，它们在处理以前先经过短时间干燥，水用作溶剂。
令人吃惊的是，已证明这一方法使用较少的加工步骤，就可制得更纯的产物。在本申请中，术语水应理解为主要由水组成的液体，它可含有直到10％的水溶性醇或酮，例如丙酮。水也可含有盐，盐可防止不希望的化合物溶解和/或促进这样的化合物沉淀。水也可含有酶类，它们可削弱植物材料的细胞结构。虽然pH值可在宽范围内变化，但它通常小于7。为了提高类黄酮的含量，经萃取的树叶可再次用水洗涤，将水完全混溶的有机溶剂加到水中，例如40％丙酮。从银杏树叶制备萃取物在本专业是已知的。就这一制备来说，将银杏树叶干燥，此后用含有一些水的醇或酮萃取它们。为了制得有足够高活性化合物含量的产物，另外的费力精制步骤是必要的，从而使生产费用增加。
为了制得高品级的产物，应从1-15年的银杏树、优选3-10年的银杏树、最优选5年的银杏树得到它的植物部分。
为了制得有适合银杏苦内酯/类黄酮比(例如1∶4或更高)的制品，水的pH值为4-7。
为了进一步提高产率，在减小尺寸以后加入酶例如纤维酶来使细胞壁破坏是有好处的。
然后用水优选进行最长3小时的萃取。
为了确保高的纯度，萃取处理宜在10-60、优选20-40℃下进行。
为制得含有所述化合物并有长的贮存期限的组合物，一个有利的实施方案涉及干燥含有所述组合物的溶液，可方便地用喷雾干燥或冷冻干燥法进行干燥。
宜从含有所述化合物的溶剂中除去溶剂，并用另外的溶剂萃取残留物。
在这一方法中，有可能制得含有所述化合物的更纯制剂。为了萃取银杏，可方便地使用甲基异丁基酮(MIK)或叔丁基醚(TBE)。
根据上述，本发明还涉及两种制剂。
本发明特别涉及一种药物制剂，它含有根据本发明的方法制得的化合物的活性组分以及药物上可接受的赋形剂或载体。
这样的药物试剂例如可用于治疗早老性痴呆病患者、长期接触有机溶剂等引起的各种症状的患者。本发明的药物制剂可以任何形式给药，特别是口服给药或胃肠给药是药优选的。
本发明还涉及一种化妆品制剂，它含有根据本发明的方法制得的化合物组成的活性组分和化妆上可接受的局部载体。
这样的化妆品制剂可有助于使皮肤保持年青和柔软。
现借助以下例证性实施方案来说明本发明。
实施例Ⅰ
在采集72小时内，将10克银杏叶与液氮(3毫升)接触。用瓷研钵将银杏叶粉碎。然后加入100毫升水以及1∶1000 W/V的UltrazymAFP-L和Cellubrix L(Novo Noridsk Ferment Ltd.,瑞士)；将它在50℃和pH值5.5下培养2小时，同时混合，随后在pH值4-5下萃取。通过在大筛目过滤器上过滤，然后例如在0.2微米亲水过滤器上进行微过滤，随后冷冻干燥的方法，从固体部分中分离出含有银杏苦内酯和类黄酮作为活性组分的液体(萃取物A)。
实施例Ⅱ
重复实施Ⅰ中描述的方法。在上述相同的方法中，用40％丙酮溶液萃取由萃取得取的残留物1小时，随后冷冻干燥(萃取物B)。
将水加到冷冻干燥的萃取物A和B中(0.1克萃取物/毫升水)。用(1∶1v/v)甲基异丁基酮(MIK)或叔丁基醚(TBE)萃取制得的溶液。这样的萃取重复2次，并将每一溶剂的留分合并。用薄膜蒸发器蒸发溶剂。
因为完全除去MIK是困难的，在蒸发以后将残留物溶于3∶2的丙酮和水的混合物(首先加入丙酮直到残留物完全溶解，然后在50℃和声化处理下逐步加入水)。随后蒸去丙酮，将水溶液冷冻干燥。
用HPLC(高压液相色谱)分析生成的残留物。使用150×3毫米ODS-3 Inertsil 5色谱柱(chrompack)。用甲醇/水(用于银杏苦内酯)或甲醇/缓冲剂55/45 v/v(用于类黄酮)作为移动相，用1毫升/分进行Isocratic洗提。缓冲剂组合物：1.2克/升磷酸二氢铵/磷酸，pH值为2.5。
白果内酯、银杏苦内酯A和B的保留时间：4.9、9.0和10.1。用折射指数检测仪测定。
类黄酮槲皮素、山柰酚和Isorametine的保留时间为8.9、15.5和16.9。在360纳米处检测。数据列入表Ⅰ
表Ⅰ
| 处理 | 银杏苦内酯 | 类黄酮*) | |
| ⅠⅡ | 水水/丙酮 | (1,57)(1,20) | (0,44)(1,04) |
| ⅢⅣ | Ⅰ+MIKⅡ+MIK | 115(35,8)19,9(30,8) | 50,8(15,8)24,5(38) |
| 合计 | 134,9 | 75,3 | |
| Ⅴ | Ⅰ+TBE | 79,4(51,1) | 15,4(9,9) |
| Ⅵ | Ⅱ+TBE | 14,0(41,3) | 5,6(16,5) |
| 合计 | 93,4 | 21 |
上表表明，用MIK和TBE萃取使产物的纯度提高。用MIK萃取使产率更高，而如果希望银杏苦内酯的产率相对于类黄酯更高，那么用TBE萃取是有用的。
Claims (13)
1．一种从植物材料中萃取化合物的方法，其中使植物材料的尺寸减小，然后用溶剂进行萃取处理，此后从含有所述化合物的溶剂中分离不溶的部分，其特征在于，用液化的气体冷冻植物材料，并在溶剂萃取以前在冷冻条件下使植物的尺寸减小。
2．根据权利要求1的方法，其特征在于，植物材料选自银杏树和Huperzia serrata的植物部分。
3．根据权利要求2的方法，其特征在于，银杏树的植物部分为新鲜的树叶，而水用作溶剂。
4．根据权利要求2或3的方法，其特征在于，银杏树的植物部分由1-15年的、优选3-10年的、最优选5年的银杏树得到。
5．根据权利要求3或4的方法，其特征在于，水的pH值为4-7
6．根据权利要求2-5中一项的方法，其特征在于，减小尺寸后将酶加入以便使细胞壁破坏。
7．根据权利要求3-6中一项的方法，其特征在于，水的萃取进行最多3小时。
8．根据权利要求3-7中一项的方法，其特征在于，在10-60、优选20-40℃下进行萃取处理。
9．根据上述权利要求中一项的方法，其特征在于，将得到的萃取物进行微过滤。
10．根据上述权利要求中一项的方法，其特征在于，通常用喷雾干燥或冷冻干燥法将含有所述化合物的溶液进行干燥。
11．根据上述权利要求中一项的方法，其特征在于，从含有所述化合物的溶剂中除去溶剂，随后用另外的溶剂萃取。
12．一种含有用上述权利要求中一项的方法制得的化合物作为活性组分以及药物上可接受的赋形剂或载体的药物制剂。
13．一种含有用上述权利中一项的方法制得的化合物作为活性组分以及化妆上可接受的局部载体的化妆品组合物。
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| DE (1) | DE69915290T2 (zh) |
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| ES (1) | ES2217770T3 (zh) |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN109954292A (zh) * | 2017-12-25 | 2019-07-02 | 山东坦途农业科技有限公司 | 药材的提取工艺 |
| CN110997151A (zh) * | 2017-05-26 | 2020-04-10 | C·巴罗纳 | 植物材料的低温分离 |
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| WO2006026713A2 (en) * | 2004-08-31 | 2006-03-09 | Tracie Martyn International, Llc | Topical benfotiamine and pyridoxamine compositions |
| US11541329B2 (en) | 2021-01-29 | 2023-01-03 | Vitalis Extraction Technology Inc. | Liquid carbon dioxide and cosolvent biomass extraction method and system |
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| SU440394A1 (ru) * | 1972-08-10 | 1974-08-25 | Институт Ботаники Им.В.Л.Комарова Ан Азербайджанской Сср | Способ получени красител из сырь растительного происхождени |
| IL81000A0 (en) * | 1985-12-20 | 1987-03-31 | Angio Medical Corp | Method for obtaining substances from animal or plants |
| US4831133A (en) * | 1987-05-01 | 1989-05-16 | Allelix, Inc. | Extraction of alkaloids of Catharanthus roseus tissue |
| DE3940091A1 (de) * | 1989-12-04 | 1991-06-06 | Schwabe Willmar Gmbh & Co | Extrakt aus blaettern von ginkgo biloba, verfahren zu seiner herstellung und den extrakt enthaltende arzneimittel |
| DE4030758A1 (de) * | 1990-09-28 | 1992-04-02 | Schwabe Willmar Gmbh & Co | Extrakt aus blaettern von ginkgo biloba, insbesondere zur intravenoesen injektion oder infusion, verfahren zu seiner herstellung und den extrakt enthaltende ampullenpraeparate |
| US5352777A (en) * | 1990-12-26 | 1994-10-04 | Pioneer Hi-Bred International, Inc. | DNA isolation from animal cells |
| JPH0690723A (ja) * | 1992-09-14 | 1994-04-05 | Kanpou Iyaku Kenkyu Shinko Zaidan | 杜仲飲料の製造方法 |
| JP3518882B2 (ja) * | 1993-11-12 | 2004-04-12 | ダイセル化学工業株式会社 | イチョウエキス及びその製造法 |
| CN1125725A (zh) * | 1994-12-28 | 1996-07-03 | 中国科学院上海药物研究所 | 一类海克林碱衍生物及它的用途 |
| JPH08208496A (ja) * | 1995-02-03 | 1996-08-13 | Akihiro Nagashima | 成分抽出用植物加工方法 |
| US5965438A (en) * | 1995-06-07 | 1999-10-12 | Phyton, Inc. | Cryopreservation of plant cells |
| CN1167153A (zh) * | 1997-06-27 | 1997-12-10 | 武汉大学 | 银杏发根的转化及其无性繁殖系的建立 |
| WO1999020291A2 (en) * | 1997-10-23 | 1999-04-29 | Pharmaprint, Inc. | Pharmaceutical grade ginkgo biloba |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN110997151A (zh) * | 2017-05-26 | 2020-04-10 | C·巴罗纳 | 植物材料的低温分离 |
| CN110997151B (zh) * | 2017-05-26 | 2021-12-21 | C·巴罗纳 | 植物材料的低温分离 |
| CN109954292A (zh) * | 2017-12-25 | 2019-07-02 | 山东坦途农业科技有限公司 | 药材的提取工艺 |
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| DE69915290T2 (de) | 2005-03-24 |
| CN1160088C (zh) | 2004-08-04 |
| US6759065B1 (en) | 2004-07-06 |
| EP1087780B1 (en) | 2004-03-03 |
| KR20010052992A (ko) | 2001-06-25 |
| JP2002518337A (ja) | 2002-06-25 |
| ES2217770T3 (es) | 2004-11-01 |
| DK1087780T3 (da) | 2004-07-12 |
| ATE260668T1 (de) | 2004-03-15 |
| WO1999065504A1 (en) | 1999-12-23 |
| DE69915290D1 (de) | 2004-04-08 |
| KR100703242B1 (ko) | 2007-04-20 |
| AU4657699A (en) | 2000-01-05 |
| EP1087780A1 (en) | 2001-04-04 |
| NL1009437C2 (nl) | 1999-12-21 |
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