CN114668789A - 木香精油在制备治疗脑癌药物或健康产品中的用途 - Google Patents
木香精油在制备治疗脑癌药物或健康产品中的用途 Download PDFInfo
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Abstract
本发明公开了一种木香精油的用途，即中药木香精油在制备治疗脑癌药物或健康产品中的应用；本发明中药木香精油在制备治疗脑癌药物或健康产品中的用途归功于木香精油显著抑制人脑瘤癌细胞、神经母瘤癌细胞的作用，IC50分别为9.4±0.51、28.46±2.57mg/mL，与木香精油的现有药物或健康产品的用途完全不同。与目前治疗脑癌的药物和健康产品相比，木香中药精油具有抑制人脑瘤癌细胞和神经母瘤癌细胞的作用，且具有良好的脂溶性，易于通过血脑屏障，因此具有提高或改善的毒理学安全性、提高或改善的代谢稳定，较长的半衰期和较小的副作用的特点。
Description
技术领域
本发明涉及医药领域，尤其涉及一种木香精油在制备治疗脑癌药物或健康产品中的用途。
背景技术
颅内肿瘤亦称为脑瘤或脑癌，是中枢神经系统最常见的疾病之一。虽然脑癌在各类癌症中所占比例仅占2％，但因其治疗难度过大而被大众周知。其中脑癌根据发病原因分为发生于脑组织、脑膜、颅神经、垂体、血管及残余胚胎组织等的原发性肿瘤及由身体其他部位的恶性肿瘤转移或侵入颅内的继发性肿瘤两类。目前脑癌的主要治疗手段为手术、放射治疗或化学治疗相结合，但治疗过后这种恶性肿瘤患者的预后和生存率水平依旧很差。尽管近些年来对于脑癌疾病和病症的检测、治疗技术不断进步，但由于发生脑癌的病因不明、治疗难度大，因脑癌所导致的死亡人数仍在持续上升，脑癌相关的疾病和病症问题亟待解决。因此，非常有必要发现新型有效的治疗或预防脑癌疾病和病症的活性分子。
木香(Aucklandia lappa Decne.)(Saussurea lappa Clarke)为菊科风毛菊属多年生高大本草植物，以其根茎入药，具有解除平滑肌痉挛、降压、抗菌、抗病毒、芳香健胃、行气止痛等功效。木香作为药用始载于《神农本草经》，列为上品。此外，菊科植物土木香(Inula helenium L.)、川木香(Vladimiria souliei)或厚叶木香(V.berardioides)、菜木香(V.edulis)、膜缘木香(V.forrestiis)、木里木香(V.muliensis.)、越西木香(V.denticulatai)以及藏木香(Inula racemosa)、总状土木香(I.racemosa)、美叶藏菊(Dolomiaea calophylla)等为木香的近缘种。
木香含有丰富的挥发油，其中以倍半萜类化合物为主。迄今，文献主要报道了木香精油具有抗肝癌、解痉、免疫调节、抗氧化、抗菌、抗寄生虫等生物活性。但是，迄今为止，尚未有文献报道木香精油具有治疗或预防脑癌的报道。
发明内容
本发明的目的在于针对现有技术的不足，提供木香精油在制备治疗脑癌药物或健康产品中的用途。
为实现上述目的，本发明采用如下技术方案：一种木香精油在制备治疗脑癌药物或健康产品中的用途。
进一步地，所述木香精油为菊科植物木香Aucklandia lappa Decne.(Saussurealappa Clarke)、土木香(Inula helenium L.)、藏木香(Inula racemosa)、川木香(Vladimiria souliei)、厚叶木香(V.berardioides)、菜木香(V.edulis)、膜缘木香(V.forrestiis)、木里木香(V.muliensis.)、越西木香(V.denticulatai)、美叶藏菊(Dolomiaea calophylla)的根、茎叶部位、果实或花絮提取的挥发性成分。
本发明所述的用途是将木香中药精油作为制备治疗脑癌药物或健康产品的有效成分，还可以加入一种或多种药物或健康产品上可接受的辅料，并可将药物制成片剂、丸剂、胶囊剂、颗粒剂、微囊片剂、混悬剂、滴丸、口服液体、注射剂、气雾剂、栓剂、皮下给药剂型中的任何一种。
所述健康产品可以为化妆品、食品、保健食品、消字号产品中的任何一种。
在本发明之前尚未发现上述木香中药精油具有抑制人脑瘤癌细胞(SF-767)和神经母瘤癌细胞(SH-SY5Y)的增值作用；也尚未发现上述木香中药精油治疗脑癌或以其为原料制备药物制剂或健康产品用于治疗脑癌疾病和病症的报道。
本发明的有益效果是：本发明首次发现木香精油具有抑制人脑瘤癌细胞(SF-767)和神经母瘤癌细胞(SH-SY5Y)增值的作用。与目前治疗脑癌的药物和健康产品相比，所述木香中药精油具有抑制人脑瘤癌细胞(SF-767)和神经母瘤癌细胞(SH-SY5Y)的作用，且具有良好的脂溶性，易于通过血脑屏障，因此具有提高或改善的毒理学安全性(即毒性降低)、提高或改善的代谢稳定，较长的半衰期或较小的副作用的特点，同时产生类似或提高的生物活性(药效)。制备的药物或健康产品可用于治疗脑癌疾病和病症。
附图说明
图1是木香精油对人脑瘤癌细胞(SF-767)抑制增殖活性示意图；
图2是木香精油对神经母瘤癌细胞(SH-SY5Y)抑制增殖活性示意图。
具体实施方式
为进一步公开而不是限制本发明，以下结合实例对本发明进一步的详细说明。下面结合附图和实施例对本发明作进一步详细说明，但本发明保护范围不局限于所述内容，实施例中方法如无特殊说明的采用常规方法，使用的试剂如无特殊说明的使用常规市售试剂或按常规方法配制的试剂。
本发明所述可药用载体包括但不限于碳酸钙、磷酸钙、硫酸钙、蔗糖、葡萄糖、乳糖、果糖、木糖醇、山梨醇、淀粉、淀粉糊、纤维素衍生物、明胶、聚乙烯吡咯烷酮、氯化钠、糊精、硬脂酸、硬脂酸镁、硬脂酸钙、植物油、聚乙二醇、无菌磷酸盐缓冲盐水、盐水、林格氏溶液以及它们的组合。
本发明所述口服剂型包括但不局限于固体口服剂型(如肠溶衣片、滴丸、口服片、咀嚼片、颗粒剂、粉末或胶囊)或液体口服剂型(如糖浆或酊剂)。此外，本发明中的木香中药精油还可以添加到食物和饮料中，用于口服施用。此外，本发明中的木香中药精油也可以配制成口香糖，以促进口服递送和吸收。
本发明所述的非口服剂型包括但不局限于通过注射或其他全身途径给药，所述其它全身途径例如经皮施用或经粘膜施用(例如经鼻、舌下、口含、经阴道或直肠，通过栓剂)。其他施用途径(例如可在兽医应用中使用的)包括肠内和胃肠外递送，包括肌肉、皮下或髓内注射，以及鞘内注射、直接脑室注射、静脉内注射、腹膜内注射、鼻内注射或眼球内注射。
本发明涉及的木香中药精油也可与其他药物活性成分联用，以制备其他的新药物组合物。
本发明的木香中药精油或其组合用以缓解脑癌症状的证实性疗效和治疗相关活性，是通过细胞模型试验进行证实的。
本发明木香中药精油或其组合的治疗作用、良好的药物代谢参数和通常无毒性使得本发明化合物成为用于治疗上述病症的理想药物和健康产品。
实施例1
采集产自云南省丽江市的云木香部，阴干干燥，将得到的干燥云木香根使用水冷式增速高效流水粉碎机粉碎，随后过药典标准筛3号筛，得到粉碎后云木香样品；将粉碎后的1kg云木香粉末放置于10L圆底烧瓶中，浸泡时间为0.1h，加水量为7L，振摇混匀，回流提取，提取时间为3h；收集回流液，用乙酸乙酯萃取3次，随后用无水硫酸钠干燥除水，获得云木香精油，得率为0.20％。
实施例2
采集产自云南省丽江市的云木香部，阴干干燥，将得到的干燥云木香根使用水冷式增速高效流水粉碎机粉碎，随后过药典标准筛3号筛，得到粉碎后云木香样品；将粉碎后的1kg云木香粉末放置于10L圆底烧瓶中，浸泡时间为1h，加水量为7L，振摇混匀，回流提取，提取时间为5h；收集回流液，用乙酸乙酯萃取3次，随后用无水硫酸钠干燥除水，获得云木香精油，得率为0.25％。
实施例3
采集产自云南省丽江市的云木香部，阴干干燥，将得到的干燥云木香根使用水冷式增速高效流水粉碎机粉碎，随后过药典标准筛3号筛，得到粉碎后云木香样品；将粉碎后的1kg云木香粉末放置于10L圆底烧瓶中，浸泡时间为2h，加水量为7L，振摇混匀，回流提取，提取时间为7h；收集回流液，用乙酸乙酯萃取3次，随后用无水硫酸钠干燥除水，获得云木香精油，得率为0.26％。
实施例4
采集产自云南省丽江市的云木香部，阴干干燥，将得到的干燥云木香根使用水冷式增速高效流水粉碎机粉碎，随后过药典标准筛3号筛，得到粉碎后云木香样品；将粉碎后的云木香粉末放置于10L圆底烧瓶中，浸泡时间为1h，加水量为8L，振摇混匀，回流提取，提取时间为3h；收集回流液，用乙酸乙酯萃取3次，随后用无水硫酸钠干燥除水，获得云木香精油，得率为0.20％。
实施例5
采集产自云南省丽江市的云木香部，阴干干燥，将得到的干燥云木香根使用水冷式增速高效流水粉碎机粉碎，随后过药典标准筛3号筛，得到粉碎后云木香样品；将粉碎后的1kg云木香粉末放置于10L圆底烧瓶中，浸泡时间为2h，加水量为8L，振摇混匀，回流提取，提取时间为5h；收集回流液，用乙酸乙酯萃取3次，随后用无水硫酸钠干燥除水，获得云木香精油，得率为0.27％。
实施例6
采集产自云南省丽江市的云木香部，阴干干燥，将得到的干燥云木香根使用水冷式增速高效流水粉碎机粉碎，随后过药典标准筛3号筛，得到粉碎后云木香样品；将粉碎后的1kg云木香粉末放置于10L圆底烧瓶中，浸泡时间为0h，加水量为8L，振摇混匀，回流提取，提取时间为7h；收集回流液，用乙酸乙酯萃取3次，随后用无水硫酸钠干燥除水，获得云木香精油，得率为0.32％。
实施例7
采集产自云南省丽江市的云木香部，阴干干燥，将得到的干燥云木香根使用水冷式增速高效流水粉碎机粉碎，随后过药典标准筛3号筛，得到粉碎后云木香样品；将粉碎后的1kg云木香粉末放置于10L圆底烧瓶中，浸泡时间为2h，加水量为9L，振摇混匀，回流提取，提取时间为3h；收集回流液，用乙酸乙酯萃取3次，随后用无水硫酸钠干燥除水，获得云木香精油，得率为0.12％。
实施例8
采集产自云南省丽江市的云木香部，阴干干燥，将得到的干燥云木香根使用水冷式增速高效流水粉碎机粉碎，随后过药典标准筛3号筛，得到粉碎后云木香样品；将粉碎后的1kg云木香粉末放置于10L圆底烧瓶中，浸泡时间为0h，加水量为9L，振摇混匀，回流提取，提取时间为5h；收集回流液，用乙酸乙酯萃取3次，随后用无水硫酸钠干燥除水，获得云木香精油，得率为0.09％。
实施例9
采集产自云南省丽江市的云木香部，阴干干燥，将得到的干燥云木香根使用水冷式增速高效流水粉碎机粉碎，随后过药典标准筛3号筛，得到粉碎后云木香样品；将粉碎后的1kg云木香粉末放置于10L圆底烧瓶中，浸泡时间为1h，加水量为9L，振摇混匀，回流提取，提取时间为7h；
(3)收集回流液，用乙酸乙酯萃取3次，随后用无水硫酸钠干燥除水，获得云木香精油，得率为0.20％。
实施例10
以精油得率为评价指标，选择浸泡时间、加水量和提取时间为考察因素，最终确定最优的提取方案为：浸泡时间位为0h、加水量为8L、提取时间为7h，云木香精油得油率高达0.32％。
实施例11
以实施例6制备得到的得油率最高的云木香精油进行GC-MS分析。所含组分按质量百分比计为去氢木香内酯(dehydrocostus lactone)(>80％)、木香烃内酯(costunolide)(>7％)、(+)-川木香内酯((+)-Mokkolactone)(>1％)、dehydrosaussurea lactone(>1％)和(+)-香橙烯((+)-Aromadendrene)(>0.2％)，具体的分析结果见表1。
表1：木香精油的GC-MS分析
实施例12：木香精油抑制人脑瘤癌细胞(SF-767)增殖实验
将预制好的云木香精油稀释为8个浓度(128,64,32,16,8,4,2,1mg/ml)。将SF-767细胞培养至对数生长期，胰酶消化，接种于96孔板(每孔200PL)，于培养箱，37℃，5％C02培养，待其融合度达到70-80％后，吸除培养液，每孔加100PL相应培养基配制的不同等比浓度的本发明云木香精油溶液，继续培养72h，然后每孔添加20PL的MTT溶液(5mg/mL)后继续孵育4h，去除培养液，每孔加入200uL二甲基亚砜，震荡5min，与490nm波长处测定样品吸光度，为防止样品本身影响，将相应培养基设置为调零孔，并以样品溶剂代替样品作为对照。
由图1可知，加入不同稀释比例的精油后，人脑瘤癌细胞的存活率明显降低，IC50为9.4±0.51mg/mL，说明云木香精油对人脑瘤癌细胞增殖产生明显的抑制作用。
实施例13：木香精油抑制神经母瘤癌细胞(SH-SY5Y)增殖实验
将预制好的云木香精油稀释为8个浓度(128,64,32,16,8,4,2,1mg/ml)。将SH-SY5Y细胞培养至对数生长期，胰酶消化，接种于96孔板(每孔200PL)，于培养箱，37℃，5％C02培养，待其融合度达到70-80％后，吸除培养液，每孔加100PL相应培养基配制的不同等比浓度的本发明云木香精油溶液，继续培养72h，然后每孔添加20PL的MTT溶液(5mg/mL)后继续孵育4h，去除培养液，每孔加入200uL二甲基亚砜，震荡5min，与490nm波长处测定样品吸光度，为防止样品本身影响，将相应培养基设置为调零孔，并以样品溶剂代替样品作为对照。
由图2可知，加入不同稀释比例的精油后，神经母瘤癌细胞的存活率明显降低，IC50为28.46±2.57mg/mL，说明云木香精油对神经母瘤癌细胞增殖产生一定的抑制作用。
上述实施例用来解释说明本发明，而不是对本发明进行限制，在本发明的精神和权利要求的保护范围内，对本发明做出的任何修改和改变，都落入本发明的保护范围。
Claims (2)
1.一种木香精油在制备治疗脑癌药物或健康产品中的用途。
2.根据权利要求1所述的用途，其特征在于，所述木香精油为菊科植物木香、土木香、藏木香、川木香、厚叶木香、菜木香、膜缘木香、木里木香、越西木香、美叶藏菊的根、茎叶部位、果实或花絮提取的挥发性成分。
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