CN114702467B - 金凤花芳香化cassane二萜类化合物、提取方法及应用 - Google Patents
金凤花芳香化cassane二萜类化合物、提取方法及应用 Download PDFInfo
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- -1 Aromatic cassane diterpenoid compound Chemical class 0.000 title claims abstract description 22
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- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 138
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- SRCZQMGIVIYBBJ-UHFFFAOYSA-N ethoxyethane;ethyl acetate Chemical compound CCOCC.CCOC(C)=O SRCZQMGIVIYBBJ-UHFFFAOYSA-N 0.000 claims description 7
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- WBKFWQBXFREOFH-UHFFFAOYSA-N dichloromethane;ethyl acetate Chemical compound ClCCl.CCOC(C)=O WBKFWQBXFREOFH-UHFFFAOYSA-N 0.000 description 1
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- A01N37/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids
- A01N37/10—Aromatic or araliphatic carboxylic acids, or thio analogues thereof; Derivatives thereof
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- A—HUMAN NECESSITIES
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- A01N37/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids
- A01N37/36—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids containing at least one carboxylic group or a thio analogue, or a derivative thereof, and a singly bound oxygen or sulfur atom attached to the same carbon skeleton, this oxygen or sulfur atom not being a member of a carboxylic group or of a thio analogue, or of a derivative thereof, e.g. hydroxy-carboxylic acids
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- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
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- A01N37/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids
- A01N37/42—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids containing within the same carbon skeleton a carboxylic group or a thio analogue, or a derivative thereof, and a carbon atom having only two bonds to hetero atoms with at the most one bond to halogen, e.g. keto-carboxylic acids
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- A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
- A01N43/02—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms
- A01N43/04—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with one hetero atom
- A01N43/06—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with one hetero atom five-membered rings
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Abstract
本发明公开了金凤花芳香化cassane二萜类化合物、提取方法及应用,包括将金凤花的茎粉碎,于醇类中热回流提取得到总浸膏;以乙酸乙酯萃取总浸膏,得到的乙酸乙酯萃取相经反复柱层析制得。本发明的化合物制备方法简单,制备得到的化合物或其药学上可接受的盐可用于制备抗菌剂制剂,经实验证明,本发明的化合物对植物菌,如猕猴桃溃疡病菌、蜡状芽孢杆菌具有较好的抗菌活性,对病原菌,如和金黄色葡萄球菌同样具有良好的抗菌活性,对环境、人、畜及其它有益生物安全。
Description
技术领域
本发明属于天然药物化学领域,具体涉及金凤花芳香化cassane二萜类化合物、提取方法及应用。
背景技术
豆科云实属植物(Caesalpinia)全属约100种,广泛分布于热带和亚热带地区,我国有17种,主要分布于西南至南部地区。据文献报道,该属植物化学成分丰富,主要有二萜、三萜、倍半萜、生物碱、皂苷、糖苷等化合物,其中cassane二萜为该属的特征性成分且具有广泛的药理活性,在抗菌、抗疟疾、抗炎和抗肿瘤等多个方面发挥着重要作用,但是目前针对芳香化cassane二萜报道较少,且未见该类二萜的抗菌活性相关报道,现仍急需进一步研究其功能活性成分,以便更好地开发其药用价值。
发明内容
针对上述现有技术的不足与缺陷,本发明的目的在于,提供一种金凤花芳香化cassane二萜类化合物、提取方法及应用。
为了达到上述目的,本申请采用如下技术方案予以实现:本发明提供一种金凤花芳香化cassane二萜类化合物,具有式1~式12所示的结构中的任意一种或多种:
一种金凤花芳香化cassane二萜类化合物的提取方法,包括将金凤花的茎粉碎,于醇类中热回流提取得到总浸膏;以乙酸乙酯萃取总浸膏,得到的乙酸乙酯萃取相经反复柱层析,即得。
更进一步的,所述的醇类包括甲醇和乙醇。
更进一步的,所述的提取方法具体包括:
将金凤花的茎阴干后粉碎到30目,于甲醇中加热回流提取得提取液,将提取液减压浓缩回收甲醇,得粗浸膏,以乙酸乙酯萃取粗浸膏,得到乙酸乙酯萃取相;
乙酸乙酯萃取相以氯仿或丙酮溶解后用硅胶进行柱层析划段粗分,以氯仿/丙酮体系进行梯度洗脱,所述氯仿/丙酮体系梯度洗脱的体积比依次为1:0、9:1、8:2、7:3、1:1和0:1;以硫酸乙醇溶液为显色剂,根据TLC显色合并相似馏分得到8个组分EA1~EA8;
其中,EA2组分用硅胶柱层析后,以石油醚/乙酸乙酯体系进行梯度洗脱,所述石油醚/乙酸乙酯体系洗脱的浓度依次为体积比30:1、25:1、20:1和10:1,根据极性大小得到8个组分2A-2H;
组分2C依次进行正向硅胶色谱柱、RP-C18反向色谱柱和Sephadx-LH20凝胶色谱柱分离,得到化合物4和5;
组分2D中析出晶体,经甲醇反复重结晶纯化得到化合物2;
组分2D的洗液依次经正向色谱柱、Sephadx-LH20凝胶色谱柱和RP-C18反向色谱柱层析分离,得到化合物3和9;
组分2E分别经RP-C18反向色谱柱、正向硅胶色谱柱和Sephadx-LH20凝胶色谱柱分离,得到化合物1和10;
组分EA3用正向硅胶柱层析,以石油醚-乙酸乙酯体系进行粗分,根据极性大小得到9个组分69A-69G,所述石油醚-乙酸乙酯体系的体积比依次为7:1、5:1、3:1和1:1;
组分69D经RP-C18半制备液相后,再经RP-C18色谱柱和Sephadx-LH20色谱柱层析,得到化合物8,所述RP-C18半制备液相使用的溶剂条件为体积浓度依次为20%、40%、60%、80%和100%的甲醇;
组分69F依次经体积比为1:1的氯仿-甲醇凝胶柱、RP-C18色谱柱和高效液相色谱制备柱得到化合物11和12;
组分69G依次经RP-C18色谱柱和Sephadx-LH20凝胶柱层析后得到化合物6;
组分EA-4经正向硅胶柱层析粗分后,根据极性大小得到组分1a-1g;组分1a采用MCI柱梯度洗脱,所述MCI柱梯度洗脱的甲醇体积浓度依次为20%、40%、60%、80%和100%;60%甲醇段再经Sephadx-LH20柱层析纯化得到化合物7。
本发明还公开了金凤花芳香化cassane二萜类化合物或其药学上可接受的盐用于制备抗菌剂制剂的应用。
更进一步的,所述抗菌剂制剂用于猕猴桃溃疡病菌、蜡状芽孢杆菌和金黄色葡萄球菌的防治。
更进一步的,所述抗菌剂制剂为加入药学上可接受的辅料按常规工艺制备成药学上可接受的制剂,所述药学上可接受的制剂为固体制剂或液体制剂。
更进一步的,所述固体制剂包括颗粒剂、胶囊剂、片剂、丸剂;所述液体制剂包括注射制剂。
更进一步的,在所述的抗菌剂制剂中,按质量百分比计,金凤花芳香化cassane二萜类化合物或其药学上可接受的盐的含量为2%~8%。
本发明与现有技术相比,有益的技术效果是:
本发明的化合物制备方法简单,制备得到的化合物或其药学上可接受的盐可用于制备抗菌剂制剂,经实验证明,本发明的化合物对植物菌,如猕猴桃溃疡病菌、蜡状芽孢杆菌具有较好的抗菌活性,对病原菌,如和金黄色葡萄球菌同样具有良好的抗菌活性,对环境、人、畜及其它有益生物安全。采用本发明的化合物制得的抗菌剂制剂可以通过口服、鼻吸入、直肠或肠胃外给药的方式施用,可将其制成常规的固体制剂、液体制剂或注射用的溶液等,优选为片剂、胶囊和注射剂。
附图说明
附图是用来提供对本公开的进一步理解,并且构成说明书的一部分,与下面的具体实施方式一起用于解释本公开,但并不构成对本公开的限制。在附图中:
图1是本发明化合物的具体分离路线图。
具体实施方式
下面将结合本发明实施例中的附图,对本发明实施例中的技术方案进行清楚、完整地描述,显然,所描述的实施例仅仅是本发明一部分实施例,而不是全部的实施例。基于本发明中的实施例,本领域普通技术人员在没有做出创造性劳动前提下所获得的所有其他实施例,都属于本发明保护的范围。
本公开的化合物可以通过多种技术获得,如化学合成方法;又如从其他云实属植物中提取获得,提取方法可以通过多种已知技术中的任一种,如:超临界流体萃取、溶剂(乙醇、甲醇、丙酮等)热回流提取、溶剂(乙醇、甲醇、丙酮等)渗滤法等。
在本公开中所用的金凤花于2019年5月采集于云南省西双版纳,经中国科学院昆明植物研究所王泽欢博士鉴定。
需要说明的是,在本发明中,根据TLC显色合并相似馏分得到8个组分,经石油醚/乙酸乙酯体系进行梯度洗脱得到的组分2A-2H,以石油醚-乙酸乙酯体系进行粗分得到的组分69A-69G,各组分均依据极性大小流出顺序进行命名,即极性小的先流出,极性大的后流出,结合TLC显色情况将相似组分进行合并后得到。
本发明的实施例中生物活性测定结果和生理生化实验结果证明,金凤花芳香化cassane二萜类化合物均具有抗菌活性。本领域技术人员将理解,生物活性测定结果和生理生化实验结果确立了金凤花芳香化cassane二萜类化合物作为抗菌剂的一般效用。
为了更好的理解发明的实质,下面用实施例来详细说明发明的技术内容,但发明并不局限于这些实施例。
实施例1:
本实施例公开了一种金凤花芳香化cassane二萜类化合物,该化合物具有式1~式12所示的结构中的任意一种或其组合:
化合物1-12的物理和光谱数据如下:
化合物1:无色针状结晶;CD(MeOH)λmax(Δε):191(+44.8),190(-36.6);UV(MeOH)λmax(logε)207(0.78)nm;IR(KBr)νmax 3494,2931,2384,2311,1724cm-1;HR-ESI-MS m/z 557.21478[M+Na]+[calcd for C31H34O8Na,557.21479];1H and 13C NMR数据见表-1。
化合物2:无色针状结晶;CD(MeOH)λmax(Δε):228(+57.9),251(-36.2);UV(MeOH)λmax(logε)215(3.87)nm;IR(KBr)νmax 3495,2929,2384,2311,1706cm-1;HR-ESI-MS m/z471.17795[M+Na]+(calcd for C27H28O6Na,471.17781);1H and 13C NMR数据见表-1。
化合物3:白色无定形粉末;CD(MeOH)λmax(Δε):191(+13.9),193(-7.9);UV(MeOH)λmax(logε)207(0.65)nm;IR(KBr)νmax 3735,3554,3535,3515,2931,2385,2312,1719cm-1;HR-ESI-MS m/z 499.20929[M+Na]+(calcd forC29H32O6Na,499.20911);1H and 13C NMR数据见表-2。
化合物4:白色无定形粉末;CD(MeOH)λmax(Δε):191(+12.5),221(-6.7);UV(MeOH)λmax(logε)218(4.39)nm;IR(KBr)νmax 3554,2927,2862,2386,2312,1709cm-1;HR-ESI-MS m/z 467.21942[M+Na]+(calcd for C29H32O4Na,467.21928);1H and 13C NMR数据见表-2。
化合物5:白色无定形粉末;CD(MeOH)λmax(Δε):278(+4.5),191(-19.2);UV(MeOH)λmax(logε)214(1.23)nm;IR(KBr)νmax3737,3598,3556,3514,3338,2927,2859,2383,2311,1705cm-1.HR-ESI-MS m/z441.20383[M+Na]+(calcd for C27H30O4Na,441.20363);1H and 13C NMR数据见表-3。
化合物6:棕色无定形粉末;CD(MeOH)λmax(Δε):190(+13.9),196(-3.6);UV(MeOH)λmax(logε)190(4.27)nm;IR(KBr)νmax3435,2928,2362,1708cm-1;HR-ESI-MS m/z 531.19801[M+Na]+(calcd for C29H32O8Na,531.19828);1Hand 13C NMR数据见表-3。
化合物7:白色无定形粉末;CD(MeOH)λmax(Δε):191(+14.5),221(-36.7);UV(MeOH)λmax(logε)219(2.10)nm;IR(KBr)νmax3392,2940,2877,2326,1731cm-1;HR-ESI-MS m/z 565.20380[M+Na]+(calcd for C29H30O10Na,565.20497)1H and 13C NMR数据见表-4。
化合物8:白色无定形粉末;CD(MeOH)λmax(Δε):238(+42.3),205(-18.5);UV(MeOH)λmax(logε)202(2.53)nm;IR(KBr)νmax 3365,2928,2384,2311,1716cm-1;HR-ESI-MS m/z 657.26697[M+Na]+(calcd for C36H42O10Na,657.26702);1H and 13C NMR数据见表-4。
化合物9:白色无定形粉末;CD(MeOH)λmax(Δε):191(+2.11),236(-40.1);UV(MeOH)λmax(logε)201(1.77)nm;IR(KBr)νmax 3397,2929,2868,2600,2547,2388,2309,1713cm-1;HR-ESI-MS m/z 431.25583[M+Na]+(calcd forC27H36O3Na,431.25567);1H and 13C NMR数据见表-5。
化合物10:白色无定形粉末;CD(MeOH)λmax(Δε):190(+7.8),234(-19.5);UV(MeOH)λmax(logε)227(1.71)nm;IR(KBr)νmax3514,2922,2856,2571,2384,2312,1742cm-1;HR-ESI-MS m/z 463.24551[M+Na]+(calcd forC27H36O5Na,463.24550);1H and 13C NMR数据见表-5。
化合物11:白色无定形粉末;CD(MeOH)λmax(Δε):190(+20.0),193(-8.8);UV(MeOH)λmax(logε)201(1.63)nm;IR(KBr)νmax 3454,2928,2860,2383,2311,1715cm-1;HR-ESI-MS m/z 509.25119[M+Na]+(calcd for C28H38O7Na,509.25097);1H and 13C NMR数据见表-6。
化合物12:无色油状;UV(MeOH)λmax(logε)230(0.71)nm;HR-ESI-MS m/z 429.22223[M+H]+(calcd for C25H33O6 429.22299);1H and13C NMR数据见表-6。
表-1化合物1和2的1H和13C-NMR数据
表-2化合物3和4的1H和13C-NMR数据
表-3化合物5和6的1H,13C-NMR数据
表-4化合物7和8的1H,13C-NMR数据
表-5化合物9和10的1H,13C-NMR数据
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表-6化合物11和12的1H,13C-NMR数据
注:上述核磁数据均采用Bruker DRX-500MHz核磁共振仪测定。
实施例2
如图1所示,本实施例公开了金凤花芳香化cassane二萜类化合物的提取方法,具体包括:
将金凤花的茎阴干,粉碎到30目,于甲醇中加热回流三次提取得提取液,将提取液减压浓缩回收甲醇得到浸膏,重复减压浓缩五次后,合并浸膏后得到总浸膏。
总浸膏用适量水分散,分别用乙酸乙酯、正丁醇各萃取五次(v/v 1:1),分别合并萃取液,减压浓缩,得到乙酸乙酯相(400g)。
乙酸乙酯萃取相以氯仿或丙酮溶解后用硅胶进行柱层析划段粗分,以氯仿/丙酮体系进行梯度洗脱,所述氯仿/丙酮体系梯度洗脱的溶剂体积比依次为1:0、9:1、8:2、7:3、1:1和0:1;以硫酸乙醇溶液为显色剂,根据TLC显色合并相似馏分得到8个组分EA1~EA8,且EA1~EA8的极性顺序由小到大;
其中,EA2组分用硅胶柱层析后,以石油醚/乙酸乙酯体系进行梯度洗脱,所述石油醚/乙酸乙酯体系洗脱的体积比依次为30:1、25:1、20:1和10:1,根据极性大小得到8个组分2A-2H,且组分2A-2H的极性顺序由小到大;
组分2C依次进行正向硅胶色谱柱、RP-C18反向色谱柱和Sephadx-LH20凝胶色谱柱(甲醇)分离,分别得化合物4和5;其中正向硅胶色谱柱采用二氯甲烷-乙酸乙酯体系进行洗脱,溶剂体积比为50:1、40:1、30:1、10:1和0:1;RP-C18反向色谱柱以甲醇-水体系洗脱,体积比为3:2、2:1、3:1和1:0;
组分2D中析出晶体,通过甲醇反复重结晶纯化得到化合物2;
组分2D的洗液依次经正向色谱柱、Sephadx-LH20(丙酮)和RP-C18柱层析分离,得到化合物3和9,其中,正向色谱柱所采用的正己烷-乙酸乙酯体系的溶剂体积比为20:1、15:1、10:1和5:1,RP-C18柱采用的丙酮-水体系的溶剂体积比为1:1、3:2、2:1;
组分2E分别经RP-C18柱、正向硅胶色谱柱和Sephadx-LH20凝胶柱(丙酮)分离后,得到化合物1和10,其中RP-C18柱以甲醇-水为洗脱溶剂,溶剂体积比为2:1、3:1和1:0,正向硅胶色谱柱采用石油醚-乙酸乙酯体系进行洗脱,体积比依次为15:1、12:1、8:1、5:1;
组分EA3用正向硅胶柱层析,以石油醚-乙酸乙酯体系进行粗分,根据极性大小得到7个组分69A-69G,且组分69A-69G的极性顺序由小到大,所述石油醚-乙酸乙酯体系的溶剂体积比依次为7:1、5:1、3:1和1:1;
组分69D经RP-C18半制备液相后再经RP-C18柱和Sephadx-LH20(丙酮)柱层析得到化合物8,其中,半制备时以梯度甲醇为溶剂,体积浓度依次为20%、40%、60%、80%和100%,RP-C18柱以甲醇-水为洗脱溶剂,体积比为2:1、3:1、4:1、1:0;
组分69F依次经凝胶色谱柱、RP-C18柱和高效液相色谱制备得到化合物11和12,其中,凝胶色谱采用氯仿-甲醇洗脱体系,体积比为1:1,RP-C18柱以甲醇-水为洗脱溶剂,溶剂体积比为3:1、4:1、5:1、1:0,高效液相色谱制备以98%甲醇为溶剂、流速为2ml/min;
组分69G先经RP-C18柱,洗脱溶剂为丙酮-水体系,体积比为4:1、5:1、6:1、1:0,再经Sephadx-LH20凝胶柱(丙酮)柱层析后得到化合物6;
组分EA-4经正向硅胶柱层析粗分后得到组分1a-1g;组分1a采用MCI柱梯度洗脱,所述MCI柱梯度洗脱的甲醇体积浓度依次为20%、40%、60%、80%和100%;60%甲醇段再经Sephadx-LH20(丙酮)柱层析纯化得到化合物7。
实施例3
采用实施例2公开的制备方法得到的化合物的抗菌活性检测:
1、供试菌株:猕猴桃溃疡病菌(Pseudomonas syringae pv.Actinidae,Psa)、蜡状芽孢杆菌(Bacillus cereus)和金黄色葡萄球菌(Staphylococcus aureus)。上述菌种均以甘油管保藏,从-80℃冰箱中取出,预先在新鲜无菌LB培养基中连续活化两次后使用。
2、活性测试方法:将细菌接种于LB培养基活化,放在37℃,170rpm/min的摇床上振荡培养至对数生长期。用LB培养基稀释菌液至2×10^6CFU/mL,取培养好的菌液加入无菌96孔板,每孔100μl。用LB培养基稀释样品及对照药至200μM。将供试化合物分别溶于DMSO配制成200mM的母液,用LB培养基将母液稀释至200μM,于96孔板中每孔中加入100μL已稀释的样品溶液,在37℃培养箱中静置培养12~14h后,观察菌体生长情况。每个样品设立三组平行,以含0.5%DMSO的LB培养基作为阴性对照,以常用抗菌药庆大霉素和环丙沙星为阳性对照,同时设置空白对照组。结合初筛结果,进一步对有显示出抑菌活性的供试化合物连续二倍稀释设置一系列浓度梯度(1.56~100μM)进行复筛。细菌在96孔板LB培养基中生长,一段时间后由于量大会产生白色沉淀,有菌生长的孔呈混浊状,底部出现沉淀,无沉淀生长的孔所对应的化合物的浓度即为最小抑菌浓度。最后,用酶标仪测试波长600nm下对应的吸光度值,以验证MIC值(最低抑菌浓度)的准确性。活性数据见表-7。
表-7化合物1-12的抑菌活性数据
表7中的数据说明化合物1-7对猕猴桃溃疡病菌、蜡状芽孢杆菌和金黄色葡萄球菌均显示出不同程度的抑菌作用。其中,以化合物2和3的抑菌效果最为显著,尤其是对蜡状芽孢杆菌和金黄色葡萄球菌,其MIC值为6.25μM,而对猕猴桃溃疡病菌抑制活性中等,MIC值分别为25和12.5μM。
同时,化合物6对蜡状芽孢杆菌也显示出显著的抗菌活性,MIC值为6.25μM。根据上述结果,化合物2、3、6抑菌效果明显,可以作为抗菌剂用于上述病菌感染的防治。
实施例4:
本实施例公开了一种片剂,该片剂包括实施例1公开的化合物中的任意一种,还包括乳糖、淀粉和硬脂酸镁。
制备方法为:将化合物、乳糖和淀粉混合,用丙二醇均匀湿润,把湿润后的混合物过筛并干燥,再过筛,加入硬脂酸镁,然后将混合物压片,每片重250mg,化合物含量为10mg。
制得的片剂用作抗菌剂,治疗病菌感染。日剂量可为0.01~10mg/kg体重,优选0.1~5mg/kg体重,可以一次或多次施用。
实施例5:
本实施例公开了一种安瓿剂,该安瓿剂由实施例1公开的化合物中的一种或多种与丙二醇混合得到,芳香化cassane二萜类化合物的含量为2%~8%;
制备方法:实施例1-2所得任一种化合物溶解于3毫升丙二醇中,过滤,将所得溶液在无菌条件下装入安瓿瓶中即得。
制得的安瓿剂用作抗菌剂,治疗病菌感染。日剂量可为0.01~10mg/kg体重,优选0.1~5mg/kg体重,可以一次或多次施用。
实施例6:
本实施例公开了一种胶囊剂,该胶囊剂包括实施例1公开的化合物10mg,乳糖187mg,硬脂酸镁3mg;
制备方法:将化合物与助剂混合,过筛,均匀混合,把得到的混合物装入硬明胶胶囊,每个胶囊重200mg,活性成分含量为10mg。日剂量可为0.01~10mg/kg体重,优选0.1~5mg/kg体重,可以一次或多次施用。
胶囊剂用作抗菌剂,治疗病菌感染。
以上结合附图详细描述了本公开的优选实施方式,但是,本公开并不限于上述实施方式中的具体细节,在本公开的技术构思范围内,可以对本公开的技术方案进行多种简单变型,这些简单变型均属于本公开的保护范围。
另外需要说明的是,在上述具体实施方式中所描述的各个具体技术特征,在不矛盾的情况下,可以通过任何合适的方式进行组合,为了避免不必要的重复,本公开对各种可能的组合方式不再另行说明。
此外,本公开的各种不同的实施方式之间也可以进行任意组合,只要其不违背本公开的思想,其同样应当视为本公开所公开的内容。
Claims (9)
1.一种金凤花芳香化cassane二萜类化合物,其特征在于,具有式7、式8、式10和式11所示结构中的任意一种或多种:
2.如权利要求1所述的金凤花芳香化cassane二萜类化合物的提取方法,其特征在于,包括将金凤花的茎粉碎,于醇类中热回流提取得到总浸膏;以乙酸乙酯萃取总浸膏,得到的乙酸乙酯萃取相经反复柱层析,即得。
3.如权利要求2所述的金凤花芳香化cassane二萜类化合物的提取方法,其特征在于,所述的醇类包括甲醇和乙醇。
4.如权利要求2所述的金凤花芳香化cassane二萜类化合物的提取方法,其特征在于,所述的提取方法具体包括:
将金凤花的茎阴干后粉碎到30目,于甲醇中加热回流提取得提取液,将提取液减压浓缩回收甲醇,得粗浸膏,以乙酸乙酯萃取粗浸膏,得到乙酸乙酯萃取相;
乙酸乙酯萃取相以氯仿或丙酮溶解后用硅胶进行柱层析划段粗分,以氯仿/丙酮体系进行梯度洗脱,所述氯仿/丙酮体系梯度洗脱的体积比依次为1:0、9:1、8:2、7:3、1:1和0:1;以硫酸乙醇溶液为显色剂,根据TLC显色合并相似馏分得到8个组分EA1~EA8;
其中,EA2组分用硅胶柱层析后,以石油醚/乙酸乙酯体系进行梯度洗脱,所述石油醚/乙酸乙酯体系洗脱的浓度依次为体积比30:1、25:1、20:1和10:1,根据极性大小得到8个组分2A-2H;
组分2E分别经RP-C18反向色谱柱、正向硅胶色谱柱和Sephadx-LH20凝胶色谱柱分离,得到化合物10;
组分EA3用正向硅胶柱层析,以石油醚-乙酸乙酯体系进行粗分,根据极性大小得到9个组分69A-69G,所述石油醚-乙酸乙酯体系的体积比依次为7:1、5:1、3:1和1:1;
组分69D经RP-C18半制备液相后,再经RP-C18色谱柱和Sephadx-LH20色谱柱层析,得到化合物8,所述RP-C18半制备液相使用的溶剂条件为体积浓度依次为20%、40%、60%、80%和100%的甲醇;
组分69F依次经体积比为1:1的氯仿-甲醇凝胶柱、RP-C18色谱柱和高效液相色谱制备柱得到化合物11;
组分EA-4经正向硅胶柱层析粗分后,根据极性大小得到组分1a-1g;组分1a采用MCI柱梯度洗脱,所述MCI柱梯度洗脱的甲醇体积浓度依次为20%、40%、60%、80%和100%;60%甲醇段再经Sephadx-LH20柱层析纯化得到化合物7。
5.权利要求1中所述的金凤花芳香化cassane二萜类化合物或其药学上可接受的盐用于制备抗菌剂制剂的应用。
6.如权利要求5所述的应用,其特征在于,所述抗菌剂制剂用于猕猴桃溃疡病菌、蜡状芽孢杆菌和金黄色葡萄球菌的防治。
7.如权利要求5所述的应用,其特征在于,所述抗菌剂制剂为加入药学上可接受的辅料按常规工艺制备成药学上可接受的制剂,所述药学上可接受的制剂为固体制剂或液体制剂。
8.如权利要求7所述的应用,其特征在于,所述固体制剂为颗粒剂、胶囊剂、片剂、丸剂;所述液体制剂为注射制剂。
9.如权利要求7所述的应用,其特征在于,在所述的抗菌剂制剂中,按质量百分比计,金凤花芳香化cassane二萜类化合物或其药学上可接受的盐的含量为2%~8%。
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