CN110054629A - 一种杜鹃花酸生物碱离子盐及其制备方法与应用 - Google Patents
一种杜鹃花酸生物碱离子盐及其制备方法与应用 Download PDFInfo
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Abstract
本发明公开了一种杜鹃花酸生物碱离子盐及其制备方法与应用,在低氧条件下,向溶解有杜鹃花酸的溶液中添加生物碱进行中和反应制得所述杜鹃花酸生物碱离子盐。所述溶解有杜鹃花酸的溶液的制备过程如下:在30~50℃下向溶剂中添加杜鹃花酸;优选地,所述杜鹃花酸的添加操作是在40℃温水浴中进行的。本发明方案制得的杜鹃花酸生物碱离子盐可应用于保湿剂、抗癌剂或抑菌剂的制备中。本发明方案制得的杜鹃花酸生物碱离子盐不仅溶解性更好,且各项功能均有所增强。
Description
技术领域
本发明涉及有机合成领域,具体涉及一种杜鹃花酸生物碱离子盐及其制备方法与应用。
背景技术
杜鹃花酸,又称壬二酸,具有良好的抗菌性,可用作食品防腐剂。在漱口用品中使用有利于龋齿的防治,在香皂中使用可避免皂体表面的开裂。对皮肤有较好的渗透性,膏霜类化妆品中使用可增加皮肤的吸收功能。有多种药效,在皮肤病膏药中可用。有亮肤和增白功能。杜鹃花酸或其锌盐与维生素B6配伍用于护发品,适用于男性内分泌较旺盛的男性荷尔蒙型脱发症的治疗,并同时能够刺激头发生长。杜鹃花原液是一种针对易生粉刺、痘痘的油性肌肤,快速去除粉刺、暗疮、痘痘,解决青春痘反复发作问题,并收紧毛孔,消除痘印的植物原液。作为一种天然植物提取液,杜鹃花原液性质温和,无刺激性,祛痘效果明显,是最新一代的祛痘药物。
生物碱是存在于自然界中的一类含氮的碱性有机化合物,有似碱的性质。大多数生物碱具有复杂的环状结构,有着显著的生物活性,目前研究表明,生物碱通常对中枢神经系统具有解热、镇痛、抗惊厥、稳定神经等作用;对心血管系统具有明显的负性频率和正性肌力的作用,有防治动脉粥样硬化、减轻心肌损伤的功能;对消化系统能够起到抗肝损伤、抗纤维化的效果;除此之外还具有抗肿瘤、抗肝癌的效果。
苦参碱和左旋肉碱是两种较为常见的生物碱。其中,苦参碱是从苦参中提取出来的一种生物碱,已报道苦参碱具有多种药理作用,包括抗炎、免疫调节等。此外,苦参碱具有利尿、抗病原体、抗氧化、改善肝功能等功效,对免疫系统具有调节作用,同时可抗过敏、抗菌。左旋肉碱是一种促使脂肪转化为能量的类氨基酸,红色肉类是左旋肉碱的主要来源,其对人体无毒副作用。不同类型的日常饮食已经含有5-100毫克的左旋肉碱,但一般人每天只能从膳食中摄入50毫克,素食者摄入更少。左旋肉碱的主要生理功能是促进脂肪转化成能量,服用左旋肉碱能够在减少身体脂肪、降低体重的同时,不减少水分和肌肉。因此,苦参碱和左旋肉碱均具有良好的生理活性。
然而,苦参碱和左旋肉碱等生物碱或杜鹃花酸由于在水中的溶解度较小,使得其应用范围受到一定的限制,因此,若能提升其溶解度,将可进一步扩大其应用范围。
发明内容
本发明所要解决的第一个技术问题是:提供一种能够提升杜鹃花酸及生物碱水溶性的杜鹃花酸生物碱离子盐的制备方法。
本发明所要解决的第二个技术问题是:提供一种上述方法制得的杜鹃花酸生物碱离子盐。
本发明所要解决的第三个技术问题是:提供一种上述杜鹃花酸生物碱离子盐的应用。
为了解决上述第一个技术问题,本发明采用的技术方案为:一种杜鹃花酸生物碱离子盐的制备方法,包括以下步骤:在低氧条件下,向溶解有杜鹃花酸的溶液中添加生物碱进行中和反应制得所述杜鹃花酸生物碱离子盐。
进一步地,所述溶解有杜鹃花酸的溶液的制备过程如下:在30~50℃下向溶剂中添加杜鹃花酸;优选地,所述杜鹃花酸的添加操作是在40℃温水浴中进行的。
进一步地,所述低氧条件为氮气氛围或惰性气体氛围。
优选地,所述溶剂为去离子水。
进一步地,所述生物碱包括苦参碱或左旋肉碱。
进一步地,所述杜鹃花酸与生物碱的摩尔比为1:(1.8~2.2);优选地,所述摩尔比为1:(1.9~2.1)。
进一步地,添加苦参碱时反应体系的温度为30~60℃;优选地,所述反应体系温度为35~45℃;最优选地,所述反应体系温度为40℃。添加完成后,可在常温下进行反应。
进一步地,所述中和反应的时间为9~16h;优选为12~13h。
进一步地,所述制备方法还包括对得到的混合溶液进行通过重结晶进行分离提纯,并对重结晶后的产物进行抽滤和干燥处理;所述干燥温度为45~65℃,时间为36~48h;优选地,干燥温度为50~55℃,时间为42-48h。
本发明的有益效果在于:本发明方案能够成功制得杜鹃花酸生物碱离子盐,制得的杜鹃花酸生物碱离子盐不仅溶解性更好,且各项功能均有所增强;本发明方案的制备方法,操作简便,后处理方便且所得产物纯度好,收率高;可采用去离子水作为溶剂,安全无害。
为了解决上述第二个技术问题,本发明采用的技术方案为:一种通过上述方法制备而得的杜鹃花酸生物碱离子盐。
本发明的有益效果在于:本发明方案的杜鹃花酸生物碱离子盐不仅具有良好的保湿、杀菌、抗癌效果,还具有去角质和促进皮肤新陈代谢的作用。
为了解决上述第三个技术问题,本发明采用的技术方案为:一种上述杜鹃花酸生物碱离子盐在保湿剂、抗癌剂或抑菌剂的制备中的应用。
本发明的有益效果在于:本发明方案的杜鹃花酸生物碱离子盐可作为保湿剂、抗癌剂和祛痘杀菌剂广泛添加于保健食品或化妆品中。
附图说明
图1为本发明实施例1制得的产物的核磁共振氢谱图;
图2为本发明实施例1制得的产物的核磁共振碳谱图;
图3为本发明实施例1制得的产物的红外谱图;
图4为本发明实施例1制得的产物的TG-DSC-DTG谱图;
图5为本发明实施例2制得的产物的核磁共振氢谱图;
图6为本发明实施例2制得的产物的核磁共振碳谱图;
图7为本发明实施例2制得的产物的红外谱图;
图8为本发明实施例2制得的产物的TG-DSC-DTG谱图。
具体实施方式
为详细说明本发明的技术内容、所实现目的及效果,以下结合实施方式并配合附图予以说明。
本发明的实施例一为:一种杜鹃花酸生物碱离子盐的制备方法,包括以下步骤:
S1、溶液配制及反应条件设定:
称取1.88g杜鹃花酸(10mmol),加入20ml去离子水,通入N2,使反应全程在N2氛围下进行,将反应容器置于温水浴(40℃)中,使温度保持在40℃,将反应容器遮光处理,保证反应在避光条件下进行。
S2、杜鹃花酸苦参碱离子盐的制备:
称取4.96g苦参碱(20mmol),杜鹃花酸与苦参碱的摩尔比为1:2,少量多次快速加入反应容器中(通常以3~5次2min内加完为宜,本实施例中,分4次将苦参碱加入到溶液中),添加过程中以40℃温水浴维持反应体系的温度。添加完毕后,撤去温水浴,在常温(20~35℃间均可,本实施例中为25℃)避光惰性气体条件下反应12h。反应完毕后,对所得反应产物进行重结晶,经过抽滤后,在真空干燥箱中50℃下干燥48h即得到杜鹃花酸苦参碱离子盐(收率95.82%,纯度99.55%)。取制得的杜鹃花酸苦参碱离子盐用核磁共振仪、红外光谱仪及热重分析仪(Thermal Gravimetric Analyzer)进行表征,得到的核磁共振氢谱图、核磁共振碳谱图、红外光谱图和热重-差示扫描量热-微分热重(Thermal Gravimetric-Differential Scanning Calorimetry-Differential Thermogravimetry,TG-DSC-DTG)谱图分别如图1、2、3和4所示。从图1-4可以看出,已成功制得了结构式正确的杜鹃花酸苦参碱离子盐。
本发明的实施例二为:一种杜鹃花酸生物碱离子盐的制备方法,包括以下步骤:
S1、溶液配制及反应条件设定:
称取1.88g杜鹃花酸(10mmol),加入20mL去离子水,通入N2,使反应全程在N2氛围下进行,将反应容器置于温水浴(40℃)中,使温度保持在40℃,将反应容器遮光处理,保证反应在避光条件下进行。
S2、杜鹃花酸左旋肉碱离子盐的制备:
称取20mmol左旋肉碱3.22g,杜鹃花酸和左旋肉碱的摩尔比为1:2,少量多次快速加入反应容器中,保证N2氛围及添加过程中实时温度为40-45℃。添加完毕后,撤去温水浴,在常温避光惰性气体条件下反应12h。反应完毕后,对所得反应产物进行重结晶,经过抽滤后,在真空干燥箱中50℃下干燥48h即得到杜鹃花酸左旋肉碱离子盐(收率:96.74%,纯度99.69%)。其核磁共振氢谱图、核磁共振碳谱图、红外谱图和TG-DSC-DTG谱图分别如图5、图6、图7和图8所示。从图5-8可以看出,已成功制得了结构式正确的杜鹃花酸左旋肉碱离子盐。
抑菌活性测试:
取上述实施例1和2制得的杜鹃花酸生物碱离子盐进行抑菌活性实验,以杜鹃花酸、苦参碱、左旋肉碱分别作为对照例1、对照例2和对照例3,具体操作如下:
1、供试菌种
市购沙门氏菌、金黄色葡萄球菌、霉菌酵母菌、大肠杆菌和枯草杆菌。
2、菌液配制
取已分离提线的二次传代的供试菌株,接种于1ml的培养基中,培养6h,血细胞计数板读数,再用普通肉汤培养基稀释至106,供用。
3、最小抑菌浓度(MIC)测定
将96微孔板经紫外线消毒4小时后,每排第1孔加入样品原液50μl,第2至11孔加入样品原液依次对数倍稀释,第1至11孔中每孔中加入上述步骤配制的菌液培养基至100μl,最后一孔为仅加菌液培养基的对照,并做阴性(培养基加菌悬液)对照,盖上96微孔板盖并用封口膜将四周包好,以保持水分并防止外界污染,包好的96微孔板于37℃恒温培养箱中静置培养24h后,用酶标仪测595nm处吸光值,并求得抑制率,平行测定3次。
抑制率(%)=(溶剂对照孔OD595nm-样品孔OD595nm)/(溶剂对照孔OD595nm-空白对照孔OD595nm)*100%。
结果如下表1所示:
表1各化合物对细菌的抑制率(MIC,mg/ml)
从上表可以看出,将实施例1~2制得的杜鹃花酸生物碱离子盐用于抗菌活性筛选,其对金黄色葡萄球菌、大肠杆菌、枯草杆菌、沙门氏菌、霉菌酵母菌等具有显著的活性。
左旋肉碱本身有促进代谢的作用,为了验证该杜鹃花酸左旋肉碱离子盐经表皮吸收能够更好地促进新陈代谢,从而降低脂肪含量和增强肌肉比例,通过体内生物实验验证该作用。
在实验中,经表皮注射杜鹃花酸左旋肉碱离子盐(100mg/kg体重)和不受热量限制(25%)的影响大鼠前肢抓地力(g/kg)表格如下表2所示(取雄性白化病大鼠48只,分为四组(n=12只/组)其中,CR:卡路里控制5天,25%的饵料进食;CAR1:左旋肉碱补充5天,剂量为68mg/kg;CAR2:杜鹃花酸左旋肉碱离子盐补充5天,剂量为100mg/kg):
表2大鼠前肢抓地力实验数据统计表
注:以上表达式为平均值±标准差(n=12)。
从上表2可以看出,制备成杜鹃花酸左旋肉碱离子盐后相对于等物质的量的左旋肉碱,在促进新陈代谢方面有得到进一步地增强。
综上所述,本发明提供的一种杜鹃花酸生物碱离子盐及其制备方法与应用,本发明方案的反应条件温和,制备条件及所需仪器均简便可得,便于工业化扩大生产,具有良好的工业应用前景;制备成离子盐后,离子盐的各项性能相对于原杜鹃花酸或生物碱均有所增强。
以上所述仅为本发明的实施例,并非因此限制本发明的专利范围,凡是利用本发明说明书及附图内容所作的等同变换,或直接或间接运用在相关的技术领域,均同理包括在本发明的专利保护范围内。
Claims (10)
1.一种杜鹃花酸生物碱离子盐的制备方法,其特征在于:包括以下步骤:在低氧条件下,向溶解有杜鹃花酸的溶液中添加生物碱进行中和反应制得所述杜鹃花酸生物碱离子盐。
2.根据权利要求1所述的杜鹃花酸生物碱离子盐的制备方法,其特征在于:所述溶解有杜鹃花酸的溶液的制备过程如下:在30~50℃下向溶剂中添加杜鹃花酸;优选地,所述杜鹃花酸的添加操作是在40℃温水浴中进行的。
3.根据权利要求2所述的杜鹃花酸生物碱离子盐的制备方法,其特征在于:所述溶剂为去离子水。
4.根据权利要求1所述的杜鹃花酸生物碱离子盐的制备方法,其特征在于:所述生物碱包括苦参碱或左旋肉碱。
5.根据权利要求1所述的杜鹃花酸生物碱离子盐的制备方法,其特征在于:所述杜鹃花酸与生物碱的摩尔比为1:(1.8~2.2);优选地,所述摩尔比为1:(1.9~2.1)。
6.根据权利要求1所述的杜鹃花酸生物碱离子盐的制备方法,其特征在于:添加苦参碱时反应体系的温度为30~60℃;优选地,所述反应体系温度为35~45℃;最优选地,所述反应体系温度为40℃。
7.根据权利要求1所述的杜鹃花酸生物碱离子盐的制备方法,其特征在于:所述中和反应的时间为9~16h;优选为12~13h。
8.根据权利要求1所述的杜鹃花酸生物碱离子盐的制备方法,其特征在于:所述制备方法还包括对得到的混合溶液进行通过重结晶进行分离提纯,并对重结晶后的产物进行抽滤和干燥处理;所述干燥温度为45~65℃,时间为36~48h;优选地,干燥温度为50~55℃,时间为42-48h。
9.一种通过如权利要求1-8任一项所述的方法制备而得的杜鹃花酸生物碱离子盐。
10.一种如权利要求9所述的杜鹃花酸生物碱离子盐在保湿剂、抗癌剂或抑菌剂的制备中的应用。
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Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN112079842A (zh) * | 2020-09-18 | 2020-12-15 | 哈尔滨工业大学(深圳) | 一种依托度酸离子盐及其制备方法与应用 |
Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20040156873A1 (en) * | 2003-02-10 | 2004-08-12 | Gupta Shyam K. | Topically Bioavailable Acne and Rosacea Treatment Compositions |
WO2004082628A2 (en) * | 2003-03-17 | 2004-09-30 | Yu Ruey J | Improved bioavailability and improved delivery of acidic pharmaceutical drugs |
WO2005049633A1 (en) * | 2003-11-03 | 2005-06-02 | Cognis Ip Management Gmbh | Acyl ribonucleosides and acyl deoxyribonucleosides |
WO2006022899A2 (en) * | 2004-08-12 | 2006-03-02 | King Industries, Inc. | Organometallic compositions and coating compositions |
WO2007000001A2 (en) * | 2005-06-27 | 2007-01-04 | Nabriva Therapeutics Forschungs Gmbh | Pleuromutilin salts with salicylic acid, azelaic acid, sebacic acid and diclofenac |
US20070269537A1 (en) * | 2003-02-10 | 2007-11-22 | Bioderm Research | Skin Condition Improvement Including Acne, Rosacea, and Topical Wounds by Artemisia Annua Extract via Iron Siderophore Trojan Horse Delivery System |
CN109481367A (zh) * | 2018-12-21 | 2019-03-19 | 深圳市萱嘉生物科技有限公司 | 一种精华液及其制备方法 |
-
2019
- 2019-03-27 CN CN201910238982.0A patent/CN110054629A/zh active Pending
Patent Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20040156873A1 (en) * | 2003-02-10 | 2004-08-12 | Gupta Shyam K. | Topically Bioavailable Acne and Rosacea Treatment Compositions |
US20070269537A1 (en) * | 2003-02-10 | 2007-11-22 | Bioderm Research | Skin Condition Improvement Including Acne, Rosacea, and Topical Wounds by Artemisia Annua Extract via Iron Siderophore Trojan Horse Delivery System |
WO2004082628A2 (en) * | 2003-03-17 | 2004-09-30 | Yu Ruey J | Improved bioavailability and improved delivery of acidic pharmaceutical drugs |
WO2005049633A1 (en) * | 2003-11-03 | 2005-06-02 | Cognis Ip Management Gmbh | Acyl ribonucleosides and acyl deoxyribonucleosides |
WO2006022899A2 (en) * | 2004-08-12 | 2006-03-02 | King Industries, Inc. | Organometallic compositions and coating compositions |
WO2007000001A2 (en) * | 2005-06-27 | 2007-01-04 | Nabriva Therapeutics Forschungs Gmbh | Pleuromutilin salts with salicylic acid, azelaic acid, sebacic acid and diclofenac |
CN109481367A (zh) * | 2018-12-21 | 2019-03-19 | 深圳市萱嘉生物科技有限公司 | 一种精华液及其制备方法 |
Non-Patent Citations (2)
Title |
---|
INES C.B.等: "Packing Interactions and Physicochemical Properties of Novel Multcomponent crystal Forms of the Anti-Inflammatary Azelaic Acid Studied by X-ray and Solid-State NMR", 《CRYSTAL GROWTH & DESIGN》 * |
LILIANA C.TOME等: "Bioactive transparent films based on polysaccharides and cholinium carboxylate ionic liquids", 《GREEN CHEMISTRY》 * |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN112079842A (zh) * | 2020-09-18 | 2020-12-15 | 哈尔滨工业大学(深圳) | 一种依托度酸离子盐及其制备方法与应用 |
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