CN114010651A - 一种改进型异槲皮苷及其制备方法和应用 - Google Patents
一种改进型异槲皮苷及其制备方法和应用 Download PDFInfo
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Abstract
本发明公开了一种改进型异槲皮苷及其制备方法和应用,改进型异槲皮苷包括异槲皮苷‑白蛋白结合体或异槲皮苷脂质体;并分别提供了异槲皮苷‑白蛋白结合体和异槲皮苷脂质体的制备方法;还提供了改进型异槲皮苷的应用,改进型异槲皮苷应用于预防和治疗中风及心脑血管疾病药物中。本发明通过改变异槲皮苷剂型,显著改善了异槲皮苷的溶解性、提高了异槲皮苷的体内生物利用度,从而明显提高了异槲皮苷对中风及相关心脑血管疾病的治疗效果。
Description
技术领域
本发明涉及改进型异槲皮苷技术领域,具体为一种改进型异槲皮苷及其制备方法和应用。
背景技术
异槲皮苷具有抗氧化、抗肿瘤、降血压、降血脂、抗炎、镇痛、抗病毒和抗抑郁等生物活性,常被用作辅助药物或药物有效成分给药,以异槲皮苷为原料合成的enzymaticallymodified isoquercetin(EMIQ)是一种新型的多用途食品添加剂,具有优质的抗氧化和着色特性,其安全性已获美国食品药品监督管理局的认证。文献报道显示异槲皮苷对中风等心脑血管疾病具有一定的改善效果,但现有的异槲皮苷在对中风等心脑血管疾病的治疗上依然存在着一定的不足,就比如:异槲皮苷水溶性差、体内生物利用度低等缺点致其治疗效果有限,难以应用于临床治疗。
针对上述问题,急需在原有异槲皮苷的基础上进行创新设计。
发明内容
本发明的目的在于提供一种改进型异槲皮苷及其制备方法和应用,通过改变异槲皮苷剂型(异槲皮苷与白蛋白结合/异槲皮苷脂质体包裹),显著改善了异槲皮苷的溶解性、提高了异槲皮苷的体内生物利用度,从而明显提高了异槲皮苷对中风及相关心脑血管疾病的治疗效果,以解决上述背景技术提出的现有问题。
为实现上述目的,本发明提供如下技术方案:一种改进型异槲皮苷,包括异槲皮苷-白蛋白结合体或异槲皮苷脂质体,效果比未改进的异槲皮苷显著提升。
本发明还提供了异槲皮苷-白蛋白结合体的制备方法,其具体步骤如下:
S1:将BSA用去离子水配成0.05mol/L的储备液,将异槲皮苷用DMSO配成0.05mol/L的储备液;
S2:将BSA储备液和异槲皮苷储备液加去离子水涡流震荡混合使最终浓度为0.005mol/L;
S3:制得的混合液经荧光光谱检测没有荧光峰。
本发明还提供了异槲皮苷脂质体的制备方法,其具体步骤如下:
S1:称取异槲皮苷、胆固醇、大豆磷脂,药脂比为1:24,胆固醇与大豆磷脂质量比为1:8,将物料置于250mL的茄形瓶中,并加入无水乙醇溶解;
S2:置于旋转蒸发仪,设定适合的水浴温度,旋蒸至无水乙醇完全回收后,茄形瓶内壁形成一层淡黄色均匀薄膜;
S3:加入5%的葡萄糖缓冲液50mL,摇晃至均匀混合,于50℃下水浴加热旋转30min,将溶液转移至烧杯中,超声分散5min,得到浅黄绿色的均一溶液,过0.45μm微孔滤膜,得到异槲皮苷脂质体;
S4:在此条件下制备的异槲皮苷脂质体包封率为100-110%,载药量为4-5%。
本发明还提供了上述改进型异槲皮苷应用于预防和治疗中风及心脑血管疾病药物中。
与现有技术相比,本发明的有益效果是:该改进型异槲皮苷及其制备方法和应用,通过实验可知,改进型异槲皮苷对氧糖剥夺再灌注(OGD/R)大鼠神经元的细胞活力改善和LDH释放抑制效果均显著好于异槲皮苷;改进型异槲皮苷对中动脉栓塞再灌注(MCAO/R)大鼠神经行为学评分、脑组织细胞损伤、神经元损伤改善效果显著好于异槲皮苷;改进型异槲皮苷对永久中动脉栓塞(pMCAO)大鼠神经行为学评分、脑组织细胞损伤、神经元损伤改善效果显著好于异槲皮苷。本发明通过改变异槲皮苷剂型(异槲皮苷与白蛋白结合/异槲皮苷脂质体包裹),显著改善了异槲皮苷的溶解性、提高了异槲皮苷的体内生物利用度,从而明显提高了异槲皮苷对中风及相关心脑血管疾病的治疗效果。
附图说明
图1为本发明异槲皮苷、相同载药量异槲皮苷白蛋白结合体及异槲皮苷脂质体对大鼠原代皮层神经元氧糖剥夺再灌注损伤的改善程度值示意图;
图2为本发明异槲皮苷、相同载药量异槲皮苷白蛋白结合体及异槲皮苷脂质体对大鼠缺血性脑损伤后神经功能的改善程度值示意图;
图3为本发明异槲皮苷、相同载药量异槲皮苷白蛋白结合体及异槲皮苷脂质体对大鼠缺血性脑损伤后大脑皮层细胞的保护作用示意图;
图4为本发明异槲皮苷、相同载药量异槲皮苷白蛋白结合体及异槲皮苷脂质体对大鼠缺血性脑损伤后大脑皮层神经元的保护作用示意图。
具体实施方式
下面将结合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。
本发明提供一种技术方案:改进型异槲皮苷为异槲皮苷-白蛋白结合体或异槲皮苷脂质体。
异槲皮苷-白蛋白结合体的制备方法,其具体步骤如下:
S1:将BSA用去离子水配成0.05mol/L的储备液,将异槲皮苷用DMSO配成0.05mol/L的储备液;
S2:将BSA储备液和异槲皮苷储备液加去离子水涡流震荡混合使最终浓度为0.005mol/L;
S3:制得的混合液经检测荧光光谱检测没有荧光峰。
异槲皮苷脂质体的制备方法,其具体步骤如下:
S1:称取异槲皮苷、胆固醇、大豆磷脂,药脂比为1:24,胆固醇与大豆磷脂质量比为1:8,将物料置于250mL的茄形瓶中,并加入无水乙醇溶解;
S2:置于旋转蒸发仪,设定适合的水浴温度,旋蒸至无水乙醇完全回收后,茄形瓶内壁形成一层淡黄色均匀薄膜;
S3:加入5%的葡萄糖缓冲液50mL,摇晃至均匀混合,于50℃下水浴加热旋转30min,将溶液转移至烧杯中,超声分散5min,得到浅黄绿色的均一溶液,过0.45μm微孔滤膜,得到异槲皮苷脂质体;
S4:在此条件下制备的异槲皮苷脂质体包封率为100-110%,载药量为4-5%。
上述改进型异槲皮苷应用于预防和治疗中风及心脑血管疾病药物中,效果比未改进的异槲皮苷显著提升。
下面进行异槲皮苷-白蛋白结合体(Isoquercetin-BSA)、异槲皮苷脂质体(Isoquercetin-Liposome)与异槲皮苷(Isoquercetin)的作用效果对比实验:
实验1
将异槲皮苷-白蛋白结合体、异槲皮苷脂质体、异槲皮苷分别作用于氧糖剥夺再灌注损伤(OGD/R)的大鼠原代皮层神经元,控制变量仅为异槲皮苷的三种不同剂型,其他条件均相同,研究三种不同剂型的异槲皮苷对大鼠原代皮层神经元氧糖剥夺再灌注损伤(OGD/R)的影响,观察大鼠神经元的细胞活力改善和LDH释放抑制效果,并绘制成柱状图,结果如图1所示,由图1可知,图a表示细胞活力(n=8),图b表示LDH释放(n=8);与Control组比较,###p<0.001;与OGD/R组比较,*p<0.05,**p<0.01,***p<0.001。则异槲皮苷-白蛋白结合体、异槲皮苷脂质体对氧糖剥夺再灌注(OGD/R)大鼠神经元的细胞活力改善和抑制LDH释放效果均显著好于异槲皮苷。
实验2
将异槲皮苷-白蛋白结合体、异槲皮苷脂质体、异槲皮苷分别作用于中动脉栓塞再灌注(MCAO/R)大鼠,控制变量仅为异槲皮苷的三种不同剂型,其他条件均相同,研究三种不同剂型的异槲皮苷对中动脉栓塞再灌注大鼠缺血性脑损伤后神经功能的影响,对大鼠神经行为学进行评分,如图2a所示;研究三种不同剂型的异槲皮苷对中动脉栓塞再灌注大鼠缺血性脑损伤的保护作用,观察大鼠脑组织细胞损伤(通过H&E染色检测),如图3a、3b所示;研究三种不同剂型的异槲皮苷对中动脉栓塞再灌注大鼠缺血性脑损伤的保护作用,观察大鼠神经元损伤(通过Nissl染色检测),如图4a、4b所示;图2a表示在大鼠脑缺血再灌注模型(MCAO/R)上,异槲皮苷的不同剂型对缺血性再灌注脑损伤大鼠神经行为的影响(n=8);图3a表示在大鼠脑缺血再灌注模型(MCAO/R)上,异槲皮苷的不同剂型对大鼠缺血性脑损伤后大脑皮层细胞的保护作用;图3b表示损伤细胞比例统计结果(n=6);图4a表示在大鼠脑缺血再灌注模型(MCAO/R)上,异槲皮苷的不同剂型对大鼠缺血性脑损伤后大脑皮层神经元的保护作用;图4b表示损伤神经元比例统计结果(n=6)。与sham组比较,###p<0.001;与MCAO/R组比较,*p<0.05,**p<0.01,***p<0.001。由图2a、3a、3b、4a、4b可知,异槲皮苷-白蛋白结合体、异槲皮苷脂质体对中动脉栓塞再灌注(MCAO/R)大鼠神经行为学评分、脑组织细胞损伤、神经元损伤改善效果显著好于异槲皮苷。
实验3
将异槲皮苷-白蛋白结合体、异槲皮苷脂质体、异槲皮苷分别作用于永久中动脉栓塞再灌注(pMCAO)大鼠,控制变量仅为异槲皮苷的三种不同剂型,其他条件均相同,研究研究三种不同剂型的异槲皮苷对永久中动脉栓塞再灌注大鼠的影响,对大鼠神经行为学进行评分,如图2b所示;研究三种不同剂型的异槲皮苷对永久中动脉栓塞再灌注大鼠缺血性脑损伤的保护作用,观察大鼠脑组织细胞损伤(通过H&E染色检测),如图3c、3d所示;研究三种不同剂型的异槲皮苷对永久中动脉栓塞再灌注大鼠缺血性脑损伤的保护作用,观察大鼠神经元损伤(通过Nissl染色检测),如图4c、4d所示;图2b表示在大鼠永久脑缺血模型(pMCAO)上,异槲皮苷不同剂型对永久脑缺血大鼠神经行为的影响(n=8);图3c表示在大鼠永久脑缺血模型(pMCAO)上,异槲皮苷不同剂型对缺血性脑损伤后大脑皮层细胞的保护作用;图3d表示损伤细胞比例统计结果(n=6);图4c表示在大鼠永久脑缺血模型(pMCAO)上,异槲皮苷不同剂型对缺血性脑损伤后大脑皮层神经元的保护作用;图4d表示损伤神经元比例统计结果(n=6)。与sham组比较,###p<0.001;与pMCAO组比较,*p<0.05,**p<0.01,***p<0.001。由图2b、3c、3d、4c、4d可知,异槲皮苷-白蛋白结合体、异槲皮苷脂质体对永久中动脉栓塞再灌注(pMCAO)大鼠神经行为学评分、脑组织细胞损伤、神经元损伤改善效果显著好于异槲皮苷。
以上实施例仅用以说明本发明的技术方案,而非对其限制;尽管参照前述实施例对本发明进行了详细的说明,本领域的普通技术人员应当理解:其依然可以对前述各实施例所记载的技术方案进行修改,或者对其中部分技术特征进行等同替换;而这些修改或者替换,并不使相应技术方案的本质脱离本发明各实施例技术方案的内容和范围。
Claims (4)
1.一种改进型异槲皮苷,其特征在于,包括异槲皮苷-白蛋白结合体或异槲皮苷脂质体。
2.一种根据权利要求1所述的改进型异槲皮苷的制备方法,其特征在于,用于制备所述异槲皮苷-白蛋白结合体,其具体步骤如下:
S1:将BSA用去离子水配成0.05mol/L的储备液,将异槲皮苷用DMSO配成0.05mol/L的储备液;
S2:将BSA储备液和异槲皮苷储备液加去离子水涡流震荡混合使最终浓度为0.005mol/L;
S3:制得的混合液经荧光光谱检测没有荧光峰。
3.一种根据权利要求1所述的改进型异槲皮苷的制备方法,其特征在于,用于制备所述异槲皮苷脂质体,其具体步骤如下:
S1:称取异槲皮苷、胆固醇、大豆磷脂,药脂比为1:24,胆固醇与大豆磷脂质量比为1:8,将物料加入到250mL的茄形瓶中,并加入无水乙醇溶解;
S2:置于旋转蒸发仪,设定适合的水浴温度,旋蒸至无水乙醇完全回收后,茄形瓶内壁形成一层淡黄色均匀薄膜;
S3:加入5%的葡萄糖缓冲液50mL,摇晃至均匀混合,于50℃下水浴加热旋蒸30min,将溶液转移至烧杯中,超声分散5min,得到浅黄绿色的均一溶液,过0.45μm微孔滤膜,得到异槲皮苷脂质体;
S4:在此条件下制备的异槲皮苷脂质体包封率为100-110%,载药量为4-5%。
4.一种根据权利要求1所述的改进型异槲皮苷的应用,其特征在于,所述改进型异槲皮苷应用于预防和治疗中风及心脑血管疾病药物中。
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