CN111838669B - 治疗改善易损脏器的纳米组合物、制剂及制备方法和用途 - Google Patents
治疗改善易损脏器的纳米组合物、制剂及制备方法和用途 Download PDFInfo
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Abstract
本发明公开了一种治疗改善易损脏器的纳米组合物、制剂及制备方法和用途,所述组合物的微观结构为纳米晶结构,组合物的有效成分主要由A类和B类原料,或者A类和C类原料,或者A类、B类和C类原料组成,其中,A类原料选自烟酰胺核糖、烟酰胺单核苷酸及其盐中的一种或多种,B类原料为非黄酮类多酚化合物,C类原料为黄酮类化合物。本发明通过将烟酰胺核糖和烟酰胺核苷酸与增效活性物质复配,并通过改变形成的组合物的微观结构,在加强作用疗效的同时,从根本上改变组合物的吸收率和利用率,进而对易损脏器进行有效的治疗和改善,克服了传统应用方式所存在的不足,能够用于治疗、预防和改善与易损脏器相关的疾病,临床应用前景良好。
Description
技术领域
本发明涉及医药及保健品技术领域,特别涉及一种治疗改善易损脏器的纳米组合物、制剂及制备方法和用途。
背景技术
烟酰胺核糖(英文缩写NR)是维生素B3的一种衍生物,可以与磷酸、腺嘌呤形成烟酰胺腺嘌呤二核苷酸(辅酶I)和烟酰胺腺嘌呤二核苷酸磷酸(辅酶II),是一种重要辅酶NAD+的前体。烟酰胺核酸在人体细胞能量生成中扮演重要角色,它参与细胞内NAD(烟酰胺腺嘌呤二核苷酸,细胞能量转化的重要辅酶)的合成。烟酰胺腺嘌呤二核苷酸(NAD,也称辅酶I)是一种转递质子(更准确来说是氢离子)的辅酶,它出现在细胞很多代谢反应中,参与蛋白质、碳水化合物和脂肪等化合物的分解,如:亮氨酸脱氢酶、甲酸氨脱氢酶、葡萄糖脱氢酶催化的手性还原都需要NAD的帮助来完成整个反应,氧化反应亦是如此。随着细胞的衰老或者病变,NAD的数量就会减少。因此,补充烟酰胺核糖,提高NAD的含量,能够提高细胞的基本代谢活动,从而显著提高细胞活力,提高人体各方面的生理机能。缺乏烟酸,会产生糙皮病,表现为皮炎、舌炎、口咽、腹泻及烦躁、失眠感觉异常等症状。
烟酰胺核糖(英文缩写NR)和烟酰胺核苷酸(英文缩写NMN)的研究逐渐成为热点,科学家们发现烟酰胺核糖和单核苷酸有许多生物学功能,能显著提高细胞活力,特别是提高衰老细胞的活力。对人体的新陈代谢、免疫力、大脑功能、心血管功能等方面都有明显的改善作用,能够通过整体提升人体机能,让体内细胞处于一种新的活跃状态,达到延缓衰老的目的。
关于烟酰胺核糖和烟酰胺核苷酸的应用,主要集中在抗衰老方面,在医药、保健品、化妆品等方面均有涉及,其应用方式也主要是将烟酰胺核糖和烟酰胺核苷酸与其他原料简单混合干燥后得到可以口服或外敷的组合物,例如作为润肤霜、面膜、面膜液、保湿乳液的原料,或作为营养胶囊、抗衰老制剂的原料。然而在这些应用中,烟酰胺核糖和烟酰胺核苷酸在脏器方面的治疗和预防作用研究甚少,虽然现有研究表明烟酰胺核糖和烟酰胺核苷酸对人体的新陈代谢、免疫力、大脑功能、心血管功能等方面都有明显的改善作用,但其与其他原料混合得到的口服制剂的实际应用效果较差,主要原因是现有方法制得的口服制剂的有效活性成分吸收率和利用率低,导致不能达到治疗和预防的目的。
中国专利CN109045037A公开了一种提升辅酶Ⅰ的抗衰老组合物、制剂及其制备方法,并具体公开了该组合物包括以下原料:甲基吡啶铬、叶酸、槲皮素、白藜芦醇、烟酰胺、烟酸、可溶性镁、亮氨酸等,该组合物或制剂可以有效提高辅酶Ⅰ(NAD)水平,可以维持人类修复DNA的能力,从而延缓衰老,该组合物或制剂也是采用简单的混合干燥方法,并且还采用需要通过多步化学法替代脂化等步骤才能变成烟酰胺核苷酸,其跟传统制备方法相同,因此,虽然增加了多种具有增效作用的组分,但并没有克服传统制备方法所存在的活性成分利用率低的问题,同时,该专利技术以NAD水平作为效果指标,而NAD并不是疾病模型疗效评价指标,因此,其说明书实验部分的技术效果只能证明提高了NAD水平,而不能证明其对易损脏器的损伤有明显的改善作用。
发明内容
本发明的发明目的在于:针对上述存在的问题,提供一种可以减轻易损脏器的损伤,促进组织器官修复的纳米组合物、制剂及制备方法和用途,通过将烟酰胺核糖和/或烟酰胺核苷酸与增效活性物质复配,并通过改变形成的组合物的微观结构,在加强作用疗效的同时,从根本上改变组合物的吸收率和利用率,进而在医学上对易损脏器进行有效的治疗和改善,克服了传统应用方式所存在的不足。
本发明采用的技术方案如下:一种治疗改善易损脏器的纳米组合物,其特征在于,所述组合物的微观结构为纳米晶结构,组合物的有效成分主要由A类和B类原料,或者A类和C类原料,或者A类、B类和C类原料组成,其中,A类原料选自烟酰胺核糖、烟酰胺单核苷酸及其盐中的一种或多种,B类原料为非黄酮类多酚化合物,C类原料为黄酮类化合物。
进一步,在本发明中,黄酮类化合物和非黄酮类多酚化合物一般为小分子活性物质,主要为天然来源,大量存在与蔬菜水果中,黄酮类化合物在防治心血管疾病,如防止动脉硬化、降低血脂和胆固醇、降低血糖、舒张血管和改善血管通透性及减少冠心病发病率等方面均具有良好的效果,能够诱发癌细胞和肿瘤细胞的凋亡,发挥抗癌抗肿瘤作用;非黄酮类多酚化合物具有抗氧化、抗炎、抗癌及心血管保护等作用,其能够抑制和减轻心血管病的发生和发展,减少人体患心血管病的风险。黄酮类化合物和非黄酮类多酚化合物作为活性成分加入,对烟酰胺核糖、烟酰胺单核苷酸及其盐等物质在治疗易损脏器方面具有增强活性效果的作用,经过发明人多年试验研究发现,黄酮类化合物和非黄酮类多酚化合物能够与NR(烟酰胺核糖)形成纳米晶结构,在该结构下,能够增加制剂的口服生物利用度和增强NR治疗易损脏器的作用,相比于简单的物理混合方式制得的制剂,通过该方式制得的制剂在人体内的降解性能和增强疗效等方面更具优势,进而提高了利用率和疗效,在宏观上表现为,本发明的组合物在医学上实现对易损脏器具有明显的治疗和改善效果,可用于治疗、预防和改善与易损脏器相关的疾病,相比于传统应用方式来说,本发明的组合物临床效果表现突出,应用前景良好。
进一步,所述B类原料选自紫檀芪、白藜芦醇、姜黄素中的一种或多种,当然也可以选择其他非黄酮类多酚化合物;所述C类原料选自儿茶素、漆黄素、槲皮素、山奈酚、木樨草素、圣草酚中的一种或多种,当然,也可以选择其他黄酮类化合物。
进一步,所述组合物的纳米晶结构为纳米球结构或/和纳米线结构。
在本发明的治疗改善易损脏器的纳米组合物中,所述组合物的三类原料重量配比关系为:A类原料1-10份,B类原料0-8份,C类原料0-5份。
作为优选,所述组合物的三类原料重量配比关系为:A类原料3份,B类原料1份,C类原料2份。
在本发明中,所述组合物由A、B、C和D四类原料组成,其中,D类原料为医学或食品中可接受的辅料或辅助性成分。
本发明的治疗改善易损脏器的纳米组合物的制备方法,包括以下步骤:
S1、按照设计的重量配比称取各原料,待用;
S2、根据原料溶解特性,将各原料分别溶于水和有机溶剂如(乙醇,丙酮,或乙酸乙酯)中,然后再混合均匀后通过纳米喷雾干燥仪制备纳米粉末,即得到纳米晶结构的组合物。
进一步,在所述纳米喷雾干燥仪中,气体流量设置为110-130L/min,喷头选用4.0-7.0um,喷头温度设置为75-105℃。
通过本发明的治疗改善易损脏器的纳米组合物所制备得到的制剂,所述制剂为口服制剂,所述口服制剂为微乳口服剂、微囊口服剂、硬胶囊剂、软胶囊剂、片剂或丸剂。
本发明的治疗改善易损脏器的制剂在制备药物或保健食品中的用途,所述药物或保健食品用于治疗、预防或/和改善与易损脏器相关的疾病,特别是用于缓解减轻与易损脏器相关的病变,同时促进组织器官的修复。
综上所述,由于采用了上述技术方案,本发明的有益效果是:本发明提供的一种可以减轻易损脏器的损伤,促进组织器官修复的纳米组合物、制剂及制备方法和用途,通过将烟酰胺核糖和/或烟酰胺核苷酸与增效活性物质复配,并通过改变形成的组合物的微观结构,在加强作用疗效的同时,从根本上改变组合物的吸收率和利用率,进而在医学上对易损脏器进行有效的治疗和改善,克服了传统应用方式所存在的不足,能够用于治疗、预防和改善与易损脏器相关的疾病,缓解和减轻与易损脏器相关的病变,同时促进组织器官的修复,临床应用前景良好。
附图说明
图1实施例1制备组合物微球的扫描电镜图;
图2实施例1制备组合物微球的XRD图谱图;
图3实施例2制备组合物微球的扫描电镜图;
图4实施例3制备组合物微球的扫描电镜图;
图5实施例5制备组合物微球的扫描电镜图;
图6实施例5制备组合物微线的XRD图谱图;
图7实施例6制备组合物微线的扫描电镜图;
图8实施例7制备组合物微线的扫描电镜图。
图9实施例8口服纳米微球制剂的组织NAD+/NADH比例分布图。
图10实施例9口服纳米微线制剂的组织NAD+/NADH比例分布图。
具体实施方式
下面结合附图,对本发明作详细的说明。
为了使本发明的目的、技术方案及优点更加清楚明白,以下结合附图及实施例,对本发明进行进一步详细说明。应当理解,此处所描述的具体实施例仅仅用以解释本发明,并不用于限定本发明。
实验材料:
原料烟酰胺核糖、白藜芦醇、儿茶素、紫檀芪、姜黄素、漆黄素、山奈酚、槲皮素均为市购产品。
实施例1:纳米微球制备
组合物配比:烟酰胺核糖120mg,白藜芦醇320mg。
制备方法:将上述原料分别溶解于去离子水和乙醇中,然后再混合均匀,经纳米喷雾干燥仪喷射制备纳米粉末,其中,选用4.0μm喷头,调节气体流量110-130L/min,喷头温度75-105℃,收集喷干粉末,经扫描电镜观测其微观形态,如图1所示;经XRD检测其结晶度,如图2所示,在图2中,与两种化合物单独的结晶峰及物理混合物的结晶峰相比,纳米微球的结晶峰显著减弱,说明其微观结构为两种化合物的分子态混合,明显区别于物理混合的结构。
实施例2:纳米微球制备
组合物配比:烟酰胺核糖200mg,白藜芦醇240mg,儿茶素40mg。
制备方法:将上述原料分别溶解于去离子水和乙醇中,然后再混合均匀,经纳米喷雾干燥仪喷射制备纳米粉末,其中,选用4.0μm喷头,调节气体流量110-130L/min,喷头温度75-105℃,收集喷干粉末,经扫描电镜观测其微观形态,如图3所示。
实施例3:纳米微球制备
组合物配比:烟酰胺核糖320mg,紫檀芪160mg,儿茶素40mg。
制备方法:将上述原料分别溶解于去离子水和乙醇中,然后再混合均匀,经纳米喷雾干燥仪喷射制备纳米粉末,其中,选用5.5μm喷头,调节气体流量110-130L/min,喷头温度75-105℃,收集喷干粉末,经扫描电镜观测其微观形态,如图4所示。
实施例4:纳米微球制备
组合物配比:烟酰胺核糖320mg,姜黄素120mg。
制备方法:将上述原料分别溶解于去离子水和乙醇中,然后再混合均匀,经纳米喷雾干燥仪喷射制备纳米粉末,其中,选用5.5μm喷头,调节气体流量110-130L/min,喷头温度75-105℃,收集喷干粉末。
实施例5:纳米微线制备
组合物配比:烟酰胺核糖200mg,漆黄素120mg。
制备方法:将上述原料分别溶解于去离子水和乙醇中,然后再混合均匀,经纳米喷雾干燥仪喷射制备纳米粉末,其中,选用4.0μm喷头,调节气体流量110-130L/min,喷头温度75-105℃,收集喷干粉末,经扫描电镜观测其微观形态,如图5所示;经XRD检测其结晶度,如图6所示,在图6中,与两种化合物单独的结晶峰及物理混合物的结晶峰相比,纳米微线的结晶峰显著减弱,说明其微观结构为两种化合物的分子态混合。
实施例6:纳米微线制备
组合物配比:烟酰胺核糖160mg,山奈酚200mg,儿茶素40mg。
制备方法:将上述原料分别溶解于去离子水和乙醇中,然后再混合均匀,经纳米喷雾干燥仪喷射制备纳米粉末,其中,选用5.5μm喷头,调节气体流量110-130L/min,喷头温度75-105℃,收集喷干粉末,经扫描电镜观测其微观形态,如图7所示。
实施例7:纳米微线制备
组合物配比:烟酰胺核糖240mg,槲皮素160mg。
制备方法:将上述原料分别溶解于去离子水和乙醇中,然后再混合均匀,经纳米喷雾干燥仪喷射制备纳米粉末,其中,选用7.0μm喷头,调节气体流量110-130L/min,喷头温度75-105℃,收集喷干粉末,经扫描电镜观测其微观形态,如图8所示。
实施例8:口服纳米微球制剂的组织NAD+/NADH比例提升情况
成年雄性C57小鼠15只(购于成都达硕生物科技有限公司),22-25g,随机分为对照组、实验组1和实验组2,每组5只。各组动物灌胃给药,连续7天,实验组给药剂量为组合物重量500微克/克体重/天(实验组1采用实施例2制备的终产物,实验组2采用实施例2中三种组分等比例的物理混合物),模型组动物给生理盐水。给药结束后24小时处死动物,取心脏,脑,肝脏,肾脏,进行组织匀浆,取上清液,商用试剂盒检测各组动物不同组织中NAD+和NADH含量。所有数据都以均数±标准差表示,并行单因素方差分析,P<0.05表示差异有统计学意义。*P<0.05和**P<0.01vs.对照组。实验结果如图9所示。由图9得到,在整体上,本发明的实施例2制备的终产物经口服吸收后对动物心脏,肝脏,肾脏中NAD+/NADH比例提升效果均优于实施例2中三种组分等比例的物理混合物的效果,特别是对心脏和肝脏组织中NAD+/NADH有较优的提升效果,并由此说明,在同组分配方的情况下,采用本发明的制备方法制备得到的具有纳米晶结构的组合物的药效明显优于简单混合制成的组合物药效,即提高了活性成分的吸收率和利用率。
实施例9:口服纳米微线制剂的组织NAD+/NADH比例提升情况
成年雄性C57小鼠15只(购于成都达硕生物科技有限公司),22-25g,随机分为对照组、实验组1和实验组2,每组5只。各组动物灌胃给药,连续7天,实验组给药剂量为组合物重量500微克/克体重/天(实验组1采用实施例6制备的终产物,实验组2采用实施例6中三种组分等比例的物理混合物),模型组动物给生理盐水。给药结束后24小时处死动物,取心脏,脑,肝脏,肾脏,进行组织匀浆,取上清液,商用试剂盒检测各组动物不同组织中NAD+NADH+含量。所有数据都以均数±标准差表示,并行单因素方差分析,P<0.05表示差异有统计学意义。*代表P<0.05和**代表P<0.01vs.对照组。实验结果如图10所示,由图10得到,在整体上,本发明的实施例6制备的终产物经口服吸收后对动物心脏,脑,肝脏中NAD+/NADH比例提升效果均优于实施例6中三种组分等比例的物理混合物的效果,特别是对脑和肝脏组织中NAD+/NADH有较优的提升效果,并由此说明,在同组分配方的情况下,采用本发明的制备方法制备得到的具有纳米晶结构的组合物的药效明显优于简单混合制成的组合物药效,即提高了活性成分的吸收率和利用率。
实施例10
成年雄性SD大鼠40只(购于成都达硕生物科技有限公司),200-250g,随机分为对照组、实验组1、实验组2和实验组3,每组10只。各组动物灌胃给药,连续7天,实验组给药剂量为组合物重量350毫克/公斤体重/天(实验组1采用实施例1制备的终产物;实验组2采用实施例1中两种组分等比例的物理混合物;实验组3采用实施例5制备的终产物,实验组4采用实施例5中两种组分等比例的物理混合物),模型组动物给生理盐水。第7天给药后,麻醉动物,采用线栓大脑中动脉制备局灶性脑缺血模型,缺血30分钟后,开放再灌注24小时。完成后,处死大鼠,各组取脑组织,部分行2mm冠状切片,TTC染色后,用Image Pro图像分析软件处理分析,计算脑梗死面积;部分行组织匀浆,取上清液,商用ELISA试剂盒测定S100β及神经元特异性烯醇化酶(NSE)的含量。所有数据都以均数±标准差表示,并行单因素方差分析,P<0.05表示差异有统计学意义。*P<0.05和**P<0.01vs.对照组。实验结果如下表1所示:
表1实施例10的实验结果
由表1可以得到,与对照组相比,治疗组脑梗死面积显著减小,S100β及神经元特异性烯醇化酶的含量都有明显降低,本发明制备的纳米晶组合物制剂对脑缺血再灌注损伤具有明显的保护作用,且疗效明显优于制剂成分的物理混合,即采用本发明的纳米晶组合物制剂对脑缺血再灌注损伤的治疗效果要明显优于制剂成分的物理混合。
实施例11
成年雄性SD大鼠40只(购于成都达硕生物科技有限公司),200-250g,随机分为对照组、实验组1、实验组2和实验组3,每组10只。各组动物灌胃给药,连续7天,实验组给药剂量为组合物重量350mg/公斤体重/天(实验组1采用实施例2制备的终产物;实验组2采用实施例2中三种组分等比例的物理混合物;实验组3采用实施例6制备的终产物,实验组4采用实施例6中三种组分等比例的物理混合物),模型组动物给生理盐水。第7天给药后,麻醉动物,摘取心脏,采用Langendorff离体心脏灌注模型,缺血30分钟,开放复灌24小时。完成后,取心脏行TTC染色;取冠脉流出液,以商用ELISA试剂盒测定肌酸激酶MB(CKMB)及肌钙蛋白I(cTnI)的含量。所有数据都以均数±标准差表示,并行单因素方差分析,P<0.05表示差异有统计学意义。*P<0.05和**P<0.01vs.对照组。实验结果如下表2所示:
表2实施例11的实验结果
由表2得到,与对照组相比,治疗组心脏梗死面积显著减小,心脏射血分数显著提高,心肌细胞中肌酸激酶MB及肌钙蛋白的含量都有明显降低,本发明制备的纳米晶组合物制剂对心肌缺血再灌注损伤具有明显的保护作用,与实验组2和4相对比得到,本发明制备的纳米晶组合物制剂的疗效明显优于制剂成分的物理混合,即采用本发明的纳米晶组合物制剂对心肌缺血再灌注损伤的治疗效果要明显优于制剂成分的物理混合。
实施例12
成年雄性C57小鼠40只(购于成都达硕生物科技有限公司),22-25g,随机分为对照组、实验组1、实验组2和实验组3,每组10只。各组动物灌胃给药,连续7天,实验组给药剂量为组合物重量500微克/克体重/天(实验组1采用实施例3制备的终产物;实验组2采用实施例3中三种组分等比例的物理混合物;实验组3采用实施例6制备的终产物,实验组4采用实施例6中三种组分等比例的物理混合物),模型组动物给生理盐水。第7天给药后,麻醉动物,采用主动脉缩窄术构建心衰模型。术后8周,心脏超声检测射血分数评估心脏功能;部分行组织匀浆,取上清液,商用ELISA试剂盒测定脑钠肽(BNP)含量。所有数据都以均数±标准差表示,并行单因素方差分析,P<0.05表示差异有统计学意义。*P<0.05和**P<0.01vs.对照组。实验结果如下表3所示:
表3实施例12的实验结果
由表3得到,与对照组相比,治疗组心脏射血分数显著提高,心肌组织中脑钠肽的含量都有明显降低,本发明制备的纳米晶组合物制剂对心衰症状具有明显的改善作用,与实验组2和4相对比得到,本发明制备的纳米晶组合物制剂的疗效明显优于制剂成分的物理混合。
因此,由实施例10-12可以总结得到,本发明的纳米晶组合物制剂对易损脏器的治疗、改善和保护效果要明显优于制剂成分的物理混合,同时还可以得到,本发明的纳米晶组合物制剂能够用于治疗、预防和改善与易损脏器相关的疾病,缓解和减轻与易损脏器相关的病变,促进组织器官的修复,临床应用前景良好。
以上所述仅为本发明的较佳实施例而已,并不用以限制本发明,凡在本发明的精神和原则之内所作的任何修改、等同替换和改进等,均应包含在本发明的保护范围之内。
Claims (5)
1.一种治疗或改善易损脏器相关疾病的纳米组合物,其特征在于,所述组合物的微观结构为纳米晶结构,组合物的有效成分由A类和B类原料,或者A类和C类原料,或者A类、B类和C类原料组成,其中,A类原料选自烟酰胺核糖、烟酰胺单核苷酸及其盐中的一种或多种,B类原料选自紫檀芪、白藜芦醇、姜黄素中的一种或多种,C类原料选自儿茶素、漆黄素、槲皮素、山奈酚中的一种或多种;所述组合物的A、B和C类原料重量配比关系为:A类原料1-10份,B类原料0-8份,C类原料0-5份,其中,B类原料与C类原料不同时为0;所述组合物的制备方法包括以下步骤:
S1、按照设计的重量配比称取各原料,待用;
S2、根据原料溶解特性,将各原料分别溶于水和乙醇中,然后再混合均匀后通过纳米喷雾干燥仪制备纳米粉末,即得到纳米晶结构的组合物;
其中,在所述纳米喷雾干燥仪中,气体流量设置为110-130L/min,喷头温度设置为75-105℃,喷头大小为4.0-7.0μm。
2.如权利要求1所述的治疗或改善易损脏器相关疾病的纳米组合物,其特征在于,所述组合物的三类原料重量配比关系为:A类原料3份,B类原料1份,C类原料2份。
3.一种治疗或改善易损脏器相关疾病的制剂,其特征在于,所述制剂由权利要求1或2所述的纳米组合物制备而成,所述制剂为口服制剂,所述口服制剂为微乳口服剂、微囊口服剂、硬胶囊剂、软胶囊剂、片剂或丸剂。
4.一种如权利要求3所述的治治疗或改善易损脏器相关疾病的制剂在制备药物中的用途,其特征在于,所述药物用于治疗、预防或/和改善与易损脏器相关的疾病。
5.如权利要求4所述的用途,其特征在于,所述药物主要用于缓解减轻与易损脏器相关的病变,同时促进组织器官的修复。
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Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
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Non-Patent Citations (2)
Title |
---|
纳米喷雾干燥技术的特点及其在药物制剂领域中的应用;陈娟等;《中国新药杂志》;20171231;第26卷(第05期);519-524 * |
纳米技术在改善中药有效成分成药性中的应用;高彩芳等;《中草药》;20180628;第49卷(第12期);2754-2762 * |
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