CN1304314A - 贯叶金丝桃提取物及其制剂 - Google Patents
贯叶金丝桃提取物及其制剂 Download PDFInfo
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- CN1304314A CN1304314A CN99807127A CN99807127A CN1304314A CN 1304314 A CN1304314 A CN 1304314A CN 99807127 A CN99807127 A CN 99807127A CN 99807127 A CN99807127 A CN 99807127A CN 1304314 A CN1304314 A CN 1304314A
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- extract
- extraction
- acid
- hypericum perforatum
- hyperforine
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- 239000000284 extract Substances 0.000 title claims abstract description 58
- 244000141009 Hypericum perforatum Species 0.000 title claims abstract description 13
- 235000017309 Hypericum perforatum Nutrition 0.000 title claims abstract description 13
- 239000000203 mixture Substances 0.000 title claims description 5
- 238000009472 formulation Methods 0.000 title description 3
- 150000002148 esters Chemical class 0.000 claims abstract description 7
- 230000001476 alcoholic effect Effects 0.000 claims abstract description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 33
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 26
- IWBJJCOKGLUQIZ-HQKKAZOISA-N hyperforin Chemical compound OC1=C(CC=C(C)C)C(=O)[C@@]2(CC=C(C)C)C[C@H](CC=C(C)C)[C@](CCC=C(C)C)(C)[C@]1(C(=O)C(C)C)C2=O IWBJJCOKGLUQIZ-HQKKAZOISA-N 0.000 claims description 20
- 229940005608 hypericin Drugs 0.000 claims description 17
- SSKVDVBQSWQEGJ-UHFFFAOYSA-N pseudohypericin Natural products C12=C(O)C=C(O)C(C(C=3C(O)=CC(O)=C4C=33)=O)=C2C3=C2C3=C4C(C)=CC(O)=C3C(=O)C3=C(O)C=C(O)C1=C32 SSKVDVBQSWQEGJ-UHFFFAOYSA-N 0.000 claims description 17
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- BTXNYTINYBABQR-UHFFFAOYSA-N hypericin Chemical compound C12=C(O)C=C(O)C(C(C=3C(O)=CC(C)=C4C=33)=O)=C2C3=C2C3=C4C(C)=CC(O)=C3C(=O)C3=C(O)C=C(O)C1=C32 BTXNYTINYBABQR-UHFFFAOYSA-N 0.000 claims description 16
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- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 9
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- -1 aliphatic ester Chemical class 0.000 claims 1
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- KZNIFHPLKGYRTM-UHFFFAOYSA-N apigenin Chemical compound C1=CC(O)=CC=C1C1=CC(=O)C2=C(O)C=C(O)C=C2O1 KZNIFHPLKGYRTM-UHFFFAOYSA-N 0.000 description 2
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- URAYPUMNDPQOKB-UHFFFAOYSA-N triacetin Chemical compound CC(=O)OCC(OC(C)=O)COC(C)=O URAYPUMNDPQOKB-UHFFFAOYSA-N 0.000 description 2
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- XFZJEEAOWLFHDH-UHFFFAOYSA-N (2R,2'R,3R,3'R,4R)-3,3',4',5,7-Pentahydroxyflavan(48)-3,3',4',5,7-pentahydroxyflavan Natural products C=12OC(C=3C=C(O)C(O)=CC=3)C(O)CC2=C(O)C=C(O)C=1C(C1=C(O)C=C(O)C=C1O1)C(O)C1C1=CC=C(O)C(O)=C1 XFZJEEAOWLFHDH-UHFFFAOYSA-N 0.000 description 1
- RTHCYVBBDHJXIQ-MRXNPFEDSA-N (R)-fluoxetine Chemical compound O([C@H](CCNC)C=1C=CC=CC=1)C1=CC=C(C(F)(F)F)C=C1 RTHCYVBBDHJXIQ-MRXNPFEDSA-N 0.000 description 1
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- DKPFZGUDAPQIHT-UHFFFAOYSA-N Butyl acetate Natural products CCCCOC(C)=O DKPFZGUDAPQIHT-UHFFFAOYSA-N 0.000 description 1
- 229920002785 Croscarmellose sodium Polymers 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- ZZZCUOFIHGPKAK-UHFFFAOYSA-N D-erythro-ascorbic acid Natural products OCC1OC(=O)C(O)=C1O ZZZCUOFIHGPKAK-UHFFFAOYSA-N 0.000 description 1
- 241000790917 Dioxys <bee> Species 0.000 description 1
- 229940123457 Free radical scavenger Drugs 0.000 description 1
- 244000068988 Glycine max Species 0.000 description 1
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- 240000005342 Hypericum chinense Species 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
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- 229920002565 Polyethylene Glycol 400 Polymers 0.000 description 1
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- CWEZAWNPTYBADX-UHFFFAOYSA-N Procyanidin Natural products OC1C(OC2C(O)C(Oc3c2c(O)cc(O)c3C4C(O)C(Oc5cc(O)cc(O)c45)c6ccc(O)c(O)c6)c7ccc(O)c(O)c7)c8c(O)cc(O)cc8OC1c9ccc(O)c(O)c9 CWEZAWNPTYBADX-UHFFFAOYSA-N 0.000 description 1
- MOJZMWJRUKIQGL-FWCKPOPSSA-N Procyanidin C2 Natural products O[C@@H]1[C@@H](c2cc(O)c(O)cc2)Oc2c([C@H]3[C@H](O)[C@@H](c4cc(O)c(O)cc4)Oc4c3c(O)cc(O)c4)c(O)cc(O)c2[C@@H]1c1c(O)cc(O)c2c1O[C@@H]([C@H](O)C2)c1cc(O)c(O)cc1 MOJZMWJRUKIQGL-FWCKPOPSSA-N 0.000 description 1
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- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
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- JCCZVLHHCNQSNM-UHFFFAOYSA-N [Na][Si] Chemical compound [Na][Si] JCCZVLHHCNQSNM-UHFFFAOYSA-N 0.000 description 1
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- JGVDBODXXHHCJH-UHFFFAOYSA-N butyl acetate;ethyl acetate Chemical compound CCOC(C)=O.CCCCOC(C)=O JGVDBODXXHHCJH-UHFFFAOYSA-N 0.000 description 1
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- 235000013773 glyceryl triacetate Nutrition 0.000 description 1
- IPCSVZSSVZVIGE-UHFFFAOYSA-N hexadecanoic acid Chemical compound CCCCCCCCCCCCCCCC(O)=O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 1
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 1
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- JLFNLZLINWHATN-UHFFFAOYSA-N pentaethylene glycol Chemical compound OCCOCCOCCOCCOCCO JLFNLZLINWHATN-UHFFFAOYSA-N 0.000 description 1
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- 150000008442 polyphenolic compounds Chemical class 0.000 description 1
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- HGVVOUNEGQIPMS-UHFFFAOYSA-N procyanidin Chemical compound O1C2=CC(O)=CC(O)=C2C(O)C(O)C1(C=1C=C(O)C(O)=CC=1)OC1CC2=C(O)C=C(O)C=C2OC1C1=CC=C(O)C(O)=C1 HGVVOUNEGQIPMS-UHFFFAOYSA-N 0.000 description 1
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Classifications
-
- 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
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/38—Clusiaceae, Hypericaceae or Guttiferae (Hypericum or Mangosteen family), e.g. common St. Johnswort
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/78—Separation; Purification; Stabilisation; Use of additives
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- Health & Medical Sciences (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medical Informatics (AREA)
- Epidemiology (AREA)
- Mycology (AREA)
- Microbiology (AREA)
- Botany (AREA)
- Biotechnology (AREA)
- Alternative & Traditional Medicine (AREA)
- Neurosurgery (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Psychiatry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pain & Pain Management (AREA)
- Medicines Containing Plant Substances (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Cosmetics (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Extraction Or Liquid Replacement (AREA)
Abstract
贯叶金丝桃的提取物,它可以通过用不溶于水的C1-C5醇的酯类分馏该植物的含水醇、醇或丙酮提取物得到的。
Description
本发明涉及贯叶金丝桃的提取物及其制剂，其中的贯叶金丝桃提取物可以通过不溶于水的C1-C5醇的酯类分馏该植物的含水醇、醇或丙酮提取物得到。
贯叶金丝桃开花的顶部含有许多类结构不同的物质，这些物质能够直接或间接作用于中枢神经系统。
实际上，人们早已知道贯叶金丝桃含有一系列的活性化合物如金丝桃素、贯叶金丝桃素和双黄酮，它们对动物和人具有抗抑郁和抗焦虑活性。这些化合物的作用机理是不相同的：抗MAO作用，对五羟色胺释放的作用，这些将在下文作详细描述，以及对苯二氮受体的活性。由于在文献中的所报道的对照数据，金丝桃素的活性已经讨论过很长时间。
最近，用体内药理模型已经证实有争论的金丝桃素抗抑郁活性。实际上，这早已被证实，即当有贯叶金丝桃提取物中所含的二聚原花青素存在下服用金丝桃素时，它具有活性(第45届药用植物研究组织年会，1997年9月7-12日，Regensburg，德国，V.Butterwecke等，摘要号011)。
最近贯叶金丝桃素已成为许多研究的目标，这些研究使贯叶金丝桃素作为抗抑郁药可能起了重要作用；由中请人所进行的试验证实了该分子具有类似于五羟色胺的活性。其他认为重要的组分是双黄酮，来自于为天然苯二氮类结构的芹菜甙元，这些报道见“天然存在的苯二氮类结构、分布和功能”，I.Izquierdo和J.Medicine Eds,1993，第33页。
这些产物，尤其是贯叶金丝桃素，在通常的提取和存放条件下是很不稳定的；按照WO97/13489(Schwabe)，贯叶金丝桃素在贯叶金丝桃素的水-醇提取物中的含量在几周后几乎下降为零。
按照WO97/13489，为了得到贯叶金丝桃素固定含量的稳定提取物，提取、纯化和存放应当在抗氧化剂如维生素C及其酯、硫酸化氨基酸等的存在下进行。
EP0599307(Schwabe)公开了通过聚乙烯吡咯烷酮和其他化学物质去除金丝桃素，金丝桃素起着所不希望的光敏作用；该专利公开了不使用抗氧化剂得到了至少5％贯叶金丝桃素含量的提取物。
比较甲醇的常规提取物或Commission E专题论文所述的那些与按照EP0599307和WO97/13489制备的提取物之间的药理和临床数据是没有意义的。另一方面，贯叶金丝桃素的常规提取物经验证含有大量黄酮及其他显著对提取物活性起作用的物质，其中所述的黄酮是潜在的自由基清除剂，因此对易氧化的物质来说是天然的稳定剂。
现在已经发现稳定的，特别是具有活性的贯叶金丝桃素的提取物，它含有对药理活性起作用的主要化合物，具体是金丝桃素、贯叶金丝桃素、黄酮类和呫吨酮，它可以通过这样的方法制得，该方法包括下列步骤：a)用醇或丙酮提取贯叶金丝桃的开花顶部；b)过滤该提取液并浓缩；c)用水或水/醇混合物稀释步骤b)中得到的浓缩物；d)用脂肪族的酯类提取步骤c)得到的含水混合液；e)把步骤d)得到的酯类提取液过滤并蒸发至干；并且，任选，f)用有机酸的含水乙醇溶液溶解并在40℃以下的温度蒸发该溶剂。
优选实现本发明的方法是用甲醇或乙醇进行第一次提取(步骤a)，药材与溶剂的重量/体积比在1∶2到1∶20的范围内，优选为1∶2到1∶10的范围内，温度在室温到溶剂的回流温度范围内，优选在室温至40℃。
用于步骤c)的脂肪族的酯类例如为乙酸乙酯、乙酸甲酯或乙酸丁酯；乙酸乙酯是最佳的。
用所述酯类提取是在用等体积的水或用体积比为1∶2到1∶5范围内的醇/水混合液处理浓缩的醇或丙酮提取液之后进行。
含水混合液与酯的体积比不是很严格的，能够在较宽的范围变化，但通常在1∶0.5到1∶2的范围内。
最好用新配制的等份溶剂重复进行提取，一般至少三次。
实现任选的步骤f)是把步骤e)中的浓缩物溶解在有机酸的95％乙醇溶液中，其中的有机酸如柠檬酸、苹果酸、乙酰天冬氨酸或磷酸。
按照M.Brolis等，色谱层析杂志，825(1998),9-16所分析的，当使用自然的植物生物量时，本发明所得到的提取物含有5-20％(重量)的贯叶金丝桃素，而当使用选择的植物生物量时可得到含量为10-50％(重量)的贯叶金丝桃素。在两种情况中，金丝桃素的总含量高于0.5％，而双黄酮是以1-2％(重量)的含量存在的。这种含量的较大差异取决于收集植物的时间、开花顶部的种子含量和该生物量中所存在的茎含量。
与总提取物相比，在各种用来评价抗抑郁和焦虑作用的药理模型中该提取物出人意料地具有较高活性，并且不需要进一步的特殊处理随着时间的推移活性是稳定的。
而且，本发明的方法不需要进一步处理就能够提供稳定的提取物。该提取物应当用任何方式遮光以避免光解。
所得到的提取物对五羟色胺(5-HT)的抑制和多巴胺(DA)的摄取具有下列活性。表Ⅰ-按照实施例1制备的贯叶金丝桃素的提取物对抑制3H 5-HT和3H DA摄取的作用。
IC50μg/ml物质 3H DA 3H 5-HT醇提取物 4.05±0.93 28.0±1.7己烷提取物 0.86±0.02 3.08±0.62实施例1 0.32±0.04 2.72±1.1贯叶金丝桃素 1.54±0.23 4.75±0.79金丝桃素 ＞50 ＞50假-金丝桃素 1.40±0.13 27.0±1.10
这些数据清楚地表明本发明的提取物具有高于贯叶金丝桃素和其他已知提取物好几倍的功效。
在体内试验中，本发明的提取物已经显示出了比已知产品高的活性，这些已知产品主要是由醇、甲醇、己烷提取物，含有或不含金丝桃素组成；而且该提取物已经证实具有较高的可重复生产性和随着时间作用的稳定性。为了在体内试验中证实抗抑郁作用，我们选择了逃逸缺陷进展试验和按照文献中已知模型在喜好酒精的Sardinia鼠上的乙醇消耗抑制试验。
在逃逸缺陷进展试验中，本发明的提取物出人意料地显示出比已知提取物高的活性和与已知药物如米帕明的相当活性。在该试验中，把小鼠固定并使其接受柔和、短暂、不可避免的电击50分钟(预试验)。24小时后，在动物的尾部试验动物避开相同刺激的能力，在这种情况下逃逸是不可能的。在30次刺激中平均一只小鼠有26次逃逸(自然对照)，而接受过预试验刺激的动物仅有1-3次脱逸(ED对照)。由预试验所诱发的高反应性没有在用抗抑郁药如米帕明或氟西汀提前治疗1-3周的小鼠中出现。在把小鼠暴露给不可避免的压力前1小时，给小鼠口服贯叶金丝桃素提取物会产生对逃逸试验的反应性有一定增加，如果提前治疗进行1-2周时，这种增加还有提高。表Ⅱ贯叶金丝桃素提取物在2周预试验的逃逸试验中对小鼠的抗抑郁作用。物质 剂量/mg/kg 逃逸数贯叶金丝桃醇提取物 1000 16.6±2.8己烷提取物 600 17.2±1.6实施例1 200 23.3±0.4实施例1 100 18.3±0.2实施例1 50 13.3±0.4对照ed -- 1.6±0.1自然对照 -- 24.1±0.1统计分析：Kruskal-Wallis 无参数ANOVA KW=13.462 p=0.0012贯叶金丝桃醇提取物对自然 p＜0.01实施例1提取的贯叶金丝桃提取物200mg/kg对自然 n.s.自然对AND p＜0.01
在按照文献已知的步骤对Sardinia小鼠的醇消耗的减少(这是抑郁和焦虑的标志)试验中，在服用3天后，与对照相比，本发明的提取物诱发了醇消耗下降75％且更倾向饮用水，而用甲醇或己烷提取物治疗后醇消耗的下降分别是30和40％。
本发明的提取物能够包括在口服制剂中，如备用溶液、软或硬明胶胶囊、片剂和控释片。在制剂中提取物的剂量在常用剂型中10到100mg/剂量和在控释制剂中高达300mg的范围内，在这种情况优选剂量是每天300mg/剂量。
以下实施例用来更详细地说明本发明。实施例1：作为活性成分的标准的贯叶金丝桃干燥提取物的制备
在25L容量的提取罐中用4×15L的甲醇提取4kg的贯叶金丝桃开花顶部。在真空下把合并的甲醇提取液浓缩到2.5L；用等体积的水稀释该浓缩物，然后用3×1.5L乙酸乙酯反向提取。过滤有机相并在真空下浓缩至干。把残余物溶于2g柠檬酸的1.3升95％乙醇溶液中。然后在真空下在不高于40℃把该有机相蒸干得到0.32kg棕黄色提取物，其含有20％的贯叶金丝桃素、0.9％的总金丝桃素(金丝桃素加假金丝桃素)和1％的双芹菜甙元。实施例2：作为活性成分的标准的贯叶金丝桃提取物的制备
收集并在不高于60℃的温度下机械干燥60kg的贯叶金丝桃开花顶部，在柔和回流下用4×20体积的丙酮提取。过滤合并的提取液以除去生物量的残余物，然后在真空下浓缩至干得到3kg提取物，该提取物含有0.4％的总金丝桃素和大约25％的贯叶金丝桃素。把该提取物悬浮在10L甲醇/水 3∶7的混合液中并用乙酸丁酯反向提取从而完成在多酚类中的抽提，用硅胶的薄层层析检查抽提，洗脱用乙酸乙酯/甲醇/H2O 100∶13.5∶10。除去水相，而把有机相在Na2SO4上干燥并在真空下不高于40℃的温度下浓缩至干得到1.6kg的干燥提取物，它含有0.7％的总金丝桃素，大约40％的贯叶金丝桃素和1.4％的双黄酮。实施例3：作为活性成分的标准的贯叶金丝桃多成分提取物的制备
收集并在不高于60℃的温度下机械干燥60kg的贯叶金丝桃开花顶部，用98％的甲醇连续提取直到可提取物提完；把甲醇提取液浓缩到30L并用等体积的水稀释浓缩液，在稀释过程中滤除不溶物；用3×30L水饱和的乙酸乙酯提取清澈的溶液，然后在Na2SO4上干燥并在真空下除去溶剂得到3.8kg的棕色提取物，它含有25％的贯叶金丝桃素、1.2％的总金丝桃素和1.2％的二聚物双黄酮。实施例4：含有实施例1制备的贯叶金丝桃的亲脂性提取物的溶液实施例1制备的贯叶金丝桃提取物 10.0g甘草酸铵 0.5g1,2-丙二醇 35.0g70％山梨醇溶液 25.0g纯化水 适量至100ml实施例5：含有实施例2制备的贯叶金丝桃提取物的包衣片实施例2制备的贯叶金丝桃提取物 300.00mg大豆多糖 54.75mg乳糖 46.00mg交联羧甲基纤维素 40.00mg钠-硅二氧化验室 20.00mg聚乙烯吡咯烷酮 5.00mg滑石 2.50mg硬脂酸镁 1.75mg包衣：羟丙基甲基纤维素 10.00mg滑石 8.50mg二氧化钛 5.00mg三醋汀 2.00mg聚山梨酯80 0.50mg氧化铁红 1.00mg
实施例6：软胶囊实施例1的贯叶金丝桃提取物 100mg单棕榈酸蔗糖 100mg聚乙二醇400 220mg甘油 15mg纯化水 15mg.
Claims (11)
1．制备贯叶金丝桃提取物的方法，它包括：a)用醇或丙酮提取贯叶金丝桃的开花顶部；b)过滤该提取液并浓缩；c)用水或水/醇混合物稀释步骤b)中得到的浓缩物；d)用脂肪族的酯类提取步骤c)得到的含水混合液；e)把步骤d)得到的酯类提取液过滤并蒸发至干；并且，任选，f)用有机酸的含水乙醇溶液溶解并在40℃以下的温度蒸发该溶剂。
2．根据权利要求1所述的方法，其中用甲醇或乙醇进行步骤a)的提取。
3．根据权利要求1所述的方法，其中用丙酮进行步骤a)的提取。
4．根据权利要求1所述的方法，其中用甲醇或乙醇进行步骤c)的稀释。
5．根据权利要求1-4中任选的一个所述的方法，其中步骤d)中所用的脂肪族酯类选自于乙酸乙酯、乙酸甲酯或乙酸丁酯。
6．根据权利要求5所述的方法，其中使用乙酸乙酯。
7．根据权利要求1所述的方法，其中任选的步骤f)的溶解在选自于在95％乙醇溶液中的柠檬酸、苹果酸、乙酰天冬氨酸或磷酸的有机酸中进行。
8．由权利要求1-7的方法得到的贯叶金丝桃提取物。
9．按照权利要求8所述的提取物，它含有10-50％(重量)的贯叶金丝桃素、高于0.5％(重量)的总金丝桃素及含量为1-2％(重量)的双黄酮类。
10．含有权利要求8或9的提取物作活性成分的药物组合物。
11．权利要求8或9的提取物在制备抗抑郁药方面的用途。
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| CN109044999A (zh) * | 2018-10-15 | 2018-12-21 | 上海市第六人民医院 | 贯叶金丝桃素在制备促进白色脂肪棕色化并且提高棕色脂肪活性的药物中的用途 |
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| ES2159270B1 (es) * | 2000-03-06 | 2002-04-01 | Asac Compania De Biotecnologia | Oleorresina de hypericum perforatum l., procedimiento de obtencion y usos. |
| AT408835B8 (de) * | 2000-05-23 | 2002-07-25 | Andreas Dipl Ing Dr Kubin | Präparation von hypericin gebunden an polyvinylpyrrolidon (pvp) verschiedenen polymerisations- und vernetzungsgrades |
| DE10213571A1 (de) * | 2002-03-26 | 2003-10-23 | Lichtwer Pharma Ag | Pflanzenextrakte und deren Anwendung |
| US20060115556A1 (en) * | 2004-12-01 | 2006-06-01 | Foulger Sidney W | Nutritional supplement drink containing xanthone extracts |
| US20060115555A1 (en) * | 2004-12-01 | 2006-06-01 | Foulger Sidney W | Nutritional supplements containing xanthone extracts |
| PT103377B (pt) * | 2005-11-02 | 2008-04-15 | Ineti Inst Nac De Engenharia E | Extratos de espécies de hypericum l. para utilização no tratamento de tuberculose persistente |
| FR2908996A1 (fr) * | 2005-11-25 | 2008-05-30 | R & D Pharma | Nouveau procede d'extraction de principes actifs et l'utilisation de ceux-ci en therapeutique |
| FR2908997B1 (fr) * | 2005-11-25 | 2014-03-14 | R Et D Pharma | Nouvelles compositions therapeutiques et le procede de production des principes actifs |
| US20080267899A1 (en) * | 2007-04-30 | 2008-10-30 | Mr. Hamit Leskaj | Plant extract composition for hair growth |
| ITMI20080316A1 (it) | 2008-02-27 | 2009-08-28 | Aboca Spa | Impiego di estratti di hypericum perforatum nel trattamento del dolore neuropatico |
| US7974647B2 (en) * | 2008-05-16 | 2011-07-05 | Mediatek Inc. | Mobile apparatus and method of timing synchronization |
| RU2541134C2 (ru) * | 2012-12-06 | 2015-02-10 | Федеральное Государственное Бюджетное Образовательное Учреждение Высшего Профессионального Образования "Дагестанский Государственный Технический Университет" (Дгту) | Способ получения сухого растительного экстракта зверобоя продырявленного |
| CN114053752A (zh) * | 2021-11-18 | 2022-02-18 | 西安天一生物技术股份有限公司 | 一种利用溶剂脱除贯叶连翘提取物中苯并芘的方法 |
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| DE19646977A1 (de) * | 1995-09-29 | 1998-01-15 | Schwabe Willmar Gmbh & Co | Stabiler Extrakt aus Hypericum perforatum L., Verfahren zu seiner Herstellung und pharmazeutische Zubereitungen |
| DE19818001C1 (de) * | 1998-04-22 | 1999-08-05 | Plantamed Arzneimittel Gmbh | Verfahren zur schonenden Gewinnung von Extraktfraktionen aus Hypericum, diese enthaltende pharmazeutische Zubereitungen und Verwendung derselben |
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- 1999-06-04 BR BR9910941-7A patent/BR9910941A/pt not_active IP Right Cessation
- 1999-06-04 PL PL99344695A patent/PL344695A1/xx unknown
- 1999-06-04 WO PCT/EP1999/003881 patent/WO1999064027A1/en not_active Application Discontinuation
- 1999-06-04 CN CN99807127A patent/CN1304314A/zh active Pending
- 1999-06-04 AU AU45070/99A patent/AU754161B2/en not_active Ceased
-
2000
- 2000-11-30 US US09/725,938 patent/US6428820B2/en not_active Expired - Fee Related
- 2000-12-07 NO NO20006229A patent/NO20006229L/no not_active Application Discontinuation
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101744890A (zh) * | 2008-12-08 | 2010-06-23 | 上海四埃美微科技有限公司 | 一种贯叶连翘提取物中金丝桃素的精制的方法 |
| CN109044999A (zh) * | 2018-10-15 | 2018-12-21 | 上海市第六人民医院 | 贯叶金丝桃素在制备促进白色脂肪棕色化并且提高棕色脂肪活性的药物中的用途 |
Also Published As
| Publication number | Publication date |
|---|---|
| IT1301678B1 (it) | 2000-07-07 |
| ITMI981311A1 (it) | 1999-12-10 |
| PL344695A1 (en) | 2001-11-19 |
| KR20010052636A (ko) | 2001-06-25 |
| HUP0102213A3 (en) | 2002-12-28 |
| NO20006229D0 (no) | 2000-12-07 |
| NO20006229L (no) | 2000-12-07 |
| JP2002517455A (ja) | 2002-06-18 |
| US20010000326A1 (en) | 2001-04-19 |
| MXPA00012178A (es) | 2003-09-25 |
| WO1999064027A1 (en) | 1999-12-16 |
| SK18702000A3 (sk) | 2001-09-11 |
| BR9910941A (pt) | 2001-03-06 |
| US6428820B2 (en) | 2002-08-06 |
| CA2334625A1 (en) | 1999-12-16 |
| HUP0102213A2 (hu) | 2002-03-28 |
| IL140150A0 (en) | 2002-02-10 |
| AU754161B2 (en) | 2002-11-07 |
| EP1089746A1 (en) | 2001-04-11 |
| AU4507099A (en) | 1999-12-30 |
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