CN109481396B - 一种富勒烯水溶液、注射剂及其制备方法 - Google Patents
一种富勒烯水溶液、注射剂及其制备方法 Download PDFInfo
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- CN109481396B CN109481396B CN201710818005.9A CN201710818005A CN109481396B CN 109481396 B CN109481396 B CN 109481396B CN 201710818005 A CN201710818005 A CN 201710818005A CN 109481396 B CN109481396 B CN 109481396B
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- fullerene
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- polyethylene glycol
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Abstract
本发明公开了一种富勒烯水溶液、注射剂及其制备方法，富勒烯水溶液溶质包括富勒烯和15‑羟基硬脂酸聚乙二醇酯，其中所述富勒烯和15‑羟基硬脂酸聚乙二醇酯质量比为(0.01‑10)：(30‑60)，具有治疗肿瘤、帕金森病、骨髓抑制剂或清除体内自由基抗衰老的作用。
Description
技术领域
本发明涉及一种富勒烯领域，尤其是涉及一种水溶性富勒烯及其制备方法
背景技术
具有笼状碳原子团簇结构的系列分子被统称为富勒烯，其是除石墨、金刚石和无定型碳之外碳元素的另一种同素异形体。富勒烯主要包括空心富勒烯、内嵌富勒烯、富勒烯衍生物及杂环富勒烯等。
富勒烯的多个P轨道构成的大π键共轭体系，使得其具有较强的接受电子的能力，因其独特的结构和理化性质，使其具有优异的清除自由基性能，被称为“自由基海绵”，同时还表现出了优异的抗氧化性能。使其在化妆品材料、生物医药等方面得到广泛关注。通过将C60嵌入表面活性剂中，C60仍可以消除细胞内的活性氧，抑制线粒体的去极化、半胱氨酸蛋白酶的激活、细胞膜上磷脂酰丝氨酸的曝光以及DNA的分裂，C60表现出了保护细胞不被氧化凋亡的作用。C60脂质体复合物通过防御UVA对皮肤结构，细胞核和胶原纤维的破坏以及向人体皮肤组织的渗透来起到抗氧化作用，是维他命C的172倍，能够亲和自由基。
现有技术中有将富勒烯C60溶于橄榄油中进行研究的报道，发现其能在不影响生理表现的情况下清除自由基并延长试验老鼠的生命，但是溶于橄榄油的富勒烯C60进入动物体内后，消化和吸收情况不是非常理想，同时，大量的油脂摄入体内后，会对体内肠道菌群产生应用，有些三高病人可能会因为摄入过多油脂而加重病情，因此直接服用油类会影响药物功效的发挥。专利WO2013/025180A1将富勒烯粉末与植物油混合，经过球磨、离心、过滤后，得到富勒烯植物油，采用直接饮用富勒烯植物油的方式来治疗疾病。口服制剂一般存在生物利用度低的问题，因此将药物制备成可注射的形式，尤其是针对癌症等恶性程度较强的病症，能更好的发挥药效治疗疾病。由于富勒烯特性，在大部分溶剂中溶解度都很差，通常溶解于芳香性溶剂中，如甲苯，氯苯等。富勒烯在水中几乎不溶解，因此，富勒烯在一般条件下难溶于水的特性制约了其在含水体系中的应用，尤其是在溶液型注射剂中应用。目前，解决富勒烯水溶性的办法主要有两大类，共价修饰和非共价修饰。其中共价修饰通过加成反应在富勒烯分子上引入氨基，羟基和/或极性侧链可改善其在水中溶解度，例如CN201210406707A使用胺基修饰富勒烯，得到富勒烯衍生物。非共价修饰在富勒烯表面引用亲水性基团以及大小合适的客体分子相包裹增大富勒烯在水中的分散性。例如CN101284660A中公开葡萄糖作为助溶物质，得到粒径在200nm左右的颗粒，CN102674312A中公开使用聚乙烯基吡咯烷酮、聚乙二醇、淀粉等助溶剂对富勒烯处理，得到粒径100-200nm的水溶性富勒烯纳米颗粒。上述专利虽然改善了富勒烯的水溶性，但是得到富勒烯粒径较大，对于注射剂来说不能够使用。CN201410088515A公开了将富勒烯粉体加入到水里利用长时间磁力和机械搅拌使粒径达到2nm，但是其利用长时间搅拌使得富勒烯外面会接上少量的水分子或者羟基进而能有很微量的溶解到水里，富勒烯在水里的浓度非常低，最高是1/1000，且长久放置会有沉淀产生。CN104983676A公开了一种水溶性富勒烯注射针剂，通过注射的方式直接将富勒烯成分输送至人体血液系统，使人体能够更快的吸收更多的富勒烯成分。富勒烯注射针剂是由重量百分比成分无菌富勒烯0.01-8％，聚氧乙基代蓖麻油45-60％，无水乙醇35-50％，用聚氧乙基代蓖麻油和无水乙醇做溶剂，能够使富勒烯充分溶解。但是该专利中其所述聚氧乙烯代蓖麻油作为乳化剂能够起到增容的效果，聚氧乙烯代蓖麻油致敏率很高，致敏机理目前尚无解释，在含量较高情况下，注射液粘度大大增加，易引起血液粥样，从而引发栓塞；并且会与常用的聚氯乙烯塑料输液器相互作用，浸出其中的邻苯二甲酸二辛酯，引起毒性；采用加入乙醇达到增溶的目的，而许多增溶剂会引起生物膜形态的改变及组织损伤；药典规定使用乙醇量最大12％，使用过多乙醇会引起药物释放过重中再沉淀，影响药物吸收利用率。
发明内容
为了解决上述技术问题，本发明的目的在于提供一种富勒烯水溶液，具有生物安全性，水中溶解度高且粒径小，能够快速吸收。
本发明的另一目的在于提供该富勒烯水溶液的制备方法，该方法简单易行，稳定性高，易于产业化生产。
本发明还有另一目的是提供含有该富勒烯水溶液的注射剂，具有低毒、低致敏性、低溶血性的能够静脉注射的注射剂。
本发明还提供了该富勒烯水溶液及其注射剂具有治疗肿瘤、帕金森病、骨髓抑制剂或清除体内自由基抗衰老的作用。
为实现上述目的，本发明是通过下述技术方案实现的：
发明人发现辅料15-羟基硬脂酸聚乙二醇酯，具有良好的生物耐受性、对富勒烯具有高溶解性，并且低毒、低致敏性、低溶血性，在含量较高情况下粘度低。采用直接静脉注射给药，作用迅速，不受pH值、酶、食物等影响，无首过效应，富勒烯直接作用于人体血液后，使得人体能够快速的吸收富勒烯，功效更好的发挥。
本发明一种技术方案，一种富勒烯水溶液，其溶质包括富勒烯和15-羟基硬脂酸聚乙二醇酯，其中所述富勒烯和15-羟基硬脂酸聚乙二醇酯质量比为(0.01-10)：(30-60)。
进一步优选，一种富勒烯水溶液，其溶质包括富勒烯粉末和15-羟基硬脂酸聚乙二醇酯，其中所述富勒烯粉末和15-羟基硬脂酸聚乙二醇酯质量比为(1-10)：(40-60)。
进一步优选，一种富勒烯水溶液，其溶质包括富勒烯和15-羟基硬脂酸聚乙二醇酯，其中所述富勒烯粉末和15-羟基硬脂酸聚乙二醇酯质量比为(4-5)：(50-60)。
本发明的富勒烯水溶液为棕黄色透明液体，其中富勒烯溶解度最高可达到3000ppm，粒径10-100nm。
优选地，上述技术方案中，所述的富勒烯为空心富勒烯和/或金属富勒烯。包括但不限于富勒烯C2n、M@C2n、M2@C2n、MA@C2n、M3N@C2n、M2C2@C2n、M2S@C2n、M2O@C2n和MxA3-xN@C2n中的任一种，其中，M和A均为金属元素，所述M和A均选自Sc、Y和镧系金属元素中的任意一种；30≤n≤60；0≤x≤3。
进一步优选所述富勒烯选择C60、C70、C76、C84一种或以上的混合物。
本发明所述的15-羟基硬脂酸聚乙二醇酯-在传统意义上是指主要为12-羟基硬脂酸和聚乙二醇通过12-羟基硬脂酸的乙氧基化获得的单酯和二酯的混合物。15-羟基硬脂酸聚乙二醇酯也称为具有α-氢-ω羟基聚(氧-1，2-乙烷二基)；12-羟基硬脂酸聚乙二醇共聚物；聚乙二醇15-羟基硬脂酸酯；聚乙二醇-15-羟基硬脂酸酯和聚乙二醇66012-羟基硬脂酸酯的12-羟基十八烷酸聚合物。在一些实施方案中，15-羟基硬脂酸聚乙二醇酯为HS15(BASFAG，Germany)。如本领域已知的，HS15由12-羟基硬脂酸的聚乙二醇单酯和二酯(即，亲脂性部分)组成，具有约30％游离的聚乙二醇(即，亲水性部分)。15-羟基硬脂酸聚乙二醇酯比吐温-80，麻油等助溶剂具有更低溶血性、低致敏性、对富勒烯高溶解性、最终注射剂粘度低，安全性高。
本发明还公开了上述富勒烯水溶液的制备方法，富勒烯与15-羟基硬脂酸聚乙二醇酯混合在一起，借助球磨机进行强力混合12-48h(优选24h)，球磨过程中控制温度在35-45度，均质，均质次数为1-7次，(优选2-5次)，最后过滤得到澄清溶液。
本发明所述的水溶液可以经口服给药，肌肉注射、皮下给药，经皮内或腹膜内给药，栓剂直肠给药或舌下含服给药。
所述的水溶液可制成药学上可接受的载体制成可接受的剂型。药学上可接受的载体以重量计可以是制剂总重量的0.1-99.9％。富勒烯油以适合药用的制剂形式存在。药用的制剂为片剂、胶囊剂、颗粒剂、丸剂、散剂、膏剂、混悬剂、注射剂、粉针剂、栓剂、霜剂、滴剂或贴剂。其中，所述片剂为糖衣片剂、薄膜衣片剂、肠溶衣片剂或缓释片剂；所述胶囊剂为硬胶囊剂、软胶囊剂、缓释胶囊剂；所述粉针剂为冻干粉针剂。
所述药物可接受的的载体选自：甘露醇、山梨醇、山梨酸或钾盐、焦亚硫酸钠、亚硫酸氢钠、硫代硫酸钠、盐酸半胱氨酸、巯基乙酸、蛋氨酸、维生素A、维生素C、维生素E、维生素D、氮酮、EDTA二钠、EDTA钙钠，一价碱金属的碳酸盐、醋酸盐、磷酸盐或其水溶液、盐酸、醋酸、硫酸、磷酸、氨基酸、氯化钠、氯化钾、乳酸钠、木糖醇、麦芽糖、葡萄糖、果糖、右旋糖苷、甘氨酸、淀粉、蔗糖、乳糖、甘露糖醇、硅衍生物、纤维素及其衍生物、藻酸盐、明胶、聚乙烯吡咯烷酮、甘油、丙二醇、乙醇、土温60-80、司班-80、蜂蜡、羊毛脂、液体石蜡、十六醇、没食子酸酯类、琼脂、三乙醇胺、碱性氨基酸、尿素、尿囊素、碳酸钙、碳酸氢钙、表面活性剂、聚乙二醇、环糊精、β－环糊精、磷脂类材料、高岭土、滑石粉、硬脂酸钙、硬脂酸镁等。
本发明的富勒烯水溶液，作为制剂形式，每剂中含有的富勒烯水溶液的有效量为0.1～1000mg，所述每剂指的是，每一制剂单位，如片剂的每片，胶囊的每粒，也可指每次服用剂量，如每次服用100mg。虽然剂量单位形式中所含活性成分的量可以变化，但一般根据所选择活性成分的效力，调节在1～1000mg范围内。
本发明的液体制剂包括溶液、悬液和乳液。例如，非胃肠道给药的注射制剂可为水或水-丙二醇溶液形式，调节其等渗度，pH等使适于活体的生理条件。液体制剂还可制成在聚乙二醇、水溶液中的溶液形式。可通过将活性成分溶解在水中，再加入适量的着色剂、调味剂、稳定剂和增稠剂，来制备口服水溶液。可将微粒化的活性成分分散在粘性物质如天然和合成胶、甲基纤维素、羧甲基纤维素钠和其它已知悬浮剂中制备适于口服的水悬液。
为了易于给药及剂量均一，将上述药物制剂配制成剂量单位形式是特别有利的。制剂的剂量单位形式指适于作为单一剂量的物理分离单位，每个单位含有产生所期望的治疗效果的计算好的预定量的活性成分。这种剂量单位形式可为包装形式，如片剂、胶囊或装在小管或小瓶中的粉剂，或装在管或瓶中的软膏、凝胶或霜剂。
本发明优选将富勒烯水溶液制成富勒烯注射剂，其包括重量百分比富勒烯水溶液30-70％，余量注射用水溶剂。
进一步优选，本发明的富勒烯注射剂，包括重量百分比富勒烯水溶液50-70％，余量注射用水溶剂。
本发明所述的注射用水溶剂主要基质为水的含溶质或不含溶质的能够用于注射的溶剂。
作为优选，所述注射用水溶剂选择生理盐水，葡萄糖注射剂、注射用水、无水乙醇中一种或以上。所述无水乙醇为USP规格无水乙醇。
进一步优选，本发明的注射用水溶剂为注射用水和无水乙醇，其体积比为(30-60)：(5-15)，优选比例为(25-38)：(8-10)。
本发明注射剂中富勒烯与15-羟基硬脂酸聚乙二醇酯的配比对其在注射用水溶剂分散性影响重大，保证富勒烯在水或乙醇介质中保持纳米形态不团聚，能够保持一定的稳定性。如果富勒烯粉末与15-羟基硬脂酸聚乙二醇酯的配比太小会影响富勒烯功效的发挥，太大会出现沉淀或悬浮状态。
所述的富勒烯注射剂还包含注射用辅料，例如PH调节剂、抗氧化剂、生物相容物质等。
所述PH调节剂选择柠檬酸、乳酸、盐酸、醋酸、磷酸、碳酸氢钠、氢氧化钠等。
本发明所述的抗氧化剂包括但不限于亚硫酸盐、抗环血酸、没食子酸丙酯、生育酚中一种或以上。
本发明所述的生物相容物质包括但不限于白蛋白，山梨醇，甘氨酸、右旋糖酐等。
本发明所述的注射液可通过静脉注射、皮下注射、肌肉注射等常规给药方式。
为了存储方便，可将注射剂冻干等工序，复溶后不影响富勒烯水溶液的分散性及溶解度。
与现有技术相比，本发明具有如下有益效果：
1、本发明采用15-羟基硬脂酸聚乙二醇酯和富勒烯充分溶解，制成的澄清浅黄褐色水溶液，稳定性强，粒径小且分布均匀，能够增强清除人体内自由基、增强机体免疫力、抗衰老、抑制肿瘤，治疗帕金森并具有显著效果。
2、利用15-羟基硬脂酸聚乙二醇酯耐高温性120℃高温不变质，终端水溶液或注射剂采用121℃高温灭菌方式进行除菌，无需昂贵的无菌制造工艺，利于产业化生产，具有极高的推广价值。
3、本发明填补了富勒烯水溶液的空白，尤其是制成水溶性的注射剂，为临床应用提供了更多选择性。
4、本发明富勒烯水溶液只引用了无毒15-羟基硬脂酸聚乙二醇酯，整个操作无需加入任何有机溶剂，富勒烯结构没有破坏，保留了富勒烯原有的生物活性。
5.HS15无致敏性，制备成HS15-富勒烯注射剂后，人体可耐受的计量较EL35注射剂要高，药效更好。
为了更好的描述本发明的有益效果，通过下述试验例来阐述
试验例一 富勒烯富勒烯水溶液的抑瘤功效
考察了富勒烯含量为1mg/ml富勒烯水溶液(按照实施例1方法制备)对小鼠肝癌肿瘤的生长抑制作用，具体如下：
动物品系：Balb/c雌鼠，5周，体重在16-20g之间；
肿瘤模型：小鼠肝癌H22瘤株；
实验分组：随机分为药物组A、药物组B和对照组C，每组6只。
给药方式：(1)向药物组A的小鼠施用1mg/ml富勒烯水溶液，静脉注射，剂量为200ul/d，连续给药10次；(2)向药物组B的小鼠施用1.2mg/ml富勒烯油组(专利WO2013/025180A1)，口服，200ml/kg/d，连续给药10次；(3)对照组C：生理盐水(Saline)；
口服；给药剂量：
实验方法：皮下接种100μL浓度为5×107/ml的H22肝癌细胞；接种24小时后开始给药，连续给药10次；实验期间每隔一天称量小鼠体重并观察肿瘤生长情况，观察至接种后15天结束实验，取小鼠肿瘤称重及测量体积，计算抑瘤率。
表1通过上述抗癌方法及抑瘤率计算得到如下结果：
| 案例 | 平均瘤重(g) | 抑瘤率 |
| A | 0.42±0.07 | 73.1％ |
| B | 0.80±0.01 | 43.6％ |
| C | 1.3±0.04 | -- |
由上表1对比可以看出，本发明的富勒烯水溶液抑制肿瘤的效率优于富勒烯油产品。
试验例二：富勒烯水溶液活体水平的化疗保护功效
动物模型：4-5周ICR小鼠，随机分为4组，每组6只，药物A组：CTX+1mg/ml富勒烯水溶液组(实施例一的注射剂)；药物B组：CTX+3mg/ml富勒烯油组(WO2013/025180A1)；对照组C：生理盐水(Saline)，实验组D；环磷酰胺(CTX)。给药方式口服，A组静脉注射，给药剂量，20ul/d：B、C、D组口服给药，给药剂量200ml/kg。小鼠皮下接种106个小鼠肝癌细胞(H22细胞)，接种5-7天后，肿瘤直径达到5mm左右时，进行实验。CTX给药量为60mg/kg小鼠体重。于肿瘤接种后第七天开始给药，作为开始实验的第一天，每天一次，连续5天，分别在第四天，第七天，第十天，第十四天和第十七天，从小鼠眼眶取血(20μl)，用血细胞自动分析仪检测血常规，其中和骨髓抑制相关的主要指标为白细胞计数(WBC)，红细胞计数(RBC)，血小板计数(PLT)，血红蛋白测定(HGB)。
实验结果：相应的检测结果如图1所示，与空白对照组相比，环磷酰胺(CTX)实验组中的小鼠中与骨髓抑制相关的指标：白细胞，红细胞，血小板，血红蛋白在小鼠体内都有着不同程度的减少，其中以白细胞的减少最为明显；而CTX+富勒烯富勒烯水溶液实验组中的小鼠，由于富勒烯的保护作用，其白细胞，红细胞，血小板，血红蛋白的量相较于环磷酰胺(CTX)实验组都有着很大程度的提高，并且随着时间的延长，相关指标越来越接近于正常小鼠的值，表明：富勒烯水溶液对于化疗药物CTX所导致的小鼠骨髓抑制有明显的保护效果。
试验例三：富勒烯富勒烯水溶液帕金森症状的改善功效
Wistar大鼠，体重180-200g。实验分5组，雌雄各半，对照组不造模，其余各组造模两周后给药，连续给药6周。富勒烯水溶液注射剂分为高剂量组(0.213mg/ml),中剂量组(0.113mg/ml)，低剂量组(0.0565mg/ml)，给药剂量为2ml，采用LPS毁损模型：阿扑吗啡(0.5mg/kg)皮下注射后能很好的模拟帕金森症状的行为学和病理改变。注射5-15分钟后诱导向健侧的旋转行为，对照组大鼠为行为变化。PD组大鼠旋转圈数随造模时间的增加而增加，给药组的大鼠旋转圈数随造模时间的延长而减少，并且高剂量组旋转圈数减少更明显。特别是高剂量组和中计量组的大鼠旋转圈数与PD组同时间相比较，第5,6周旋转天数有显著差异(P＜0.05).由表2中数据可以得出富勒烯水溶液对于LPS诱导的老年痴呆症有显著效果
表2大鼠旋转行为变化(转/分钟)
试验例四 本发明富勒烯水溶液抗衰老作用：
对于采用本发明方法所得到的HS15-C60，采用自旋捕获法(ESR)测定自由基去除效果。具体操作为：对于过氧化氢与亚铁离子反应产生的自由基，利用DMPO(5,5-二甲基-1-吡咯啉-N-氧化物)作为自旋捕获剂，检测DMPO与羟基自由基反应生成的产物DMPO-OH的信号。
实际测试中：七水合硫酸亚铁的浓度为0.4mmol/L，双氧水的质量浓度为5％，PBS的pH值为7.4，HS15-C60中C60的浓度为1mg/ML，DMPO的浓度为0.4mol/L，各取以上五种溶液50μL混合均匀后进行测试。从图4中可以看出所得HS15-富勒烯对羟基自由基的清除效率非常高。
附图说明
图1富勒烯富勒烯水溶液活体水平的化疗保护功效
图2是根据本发明的富勒烯水溶液微观结构图，
图3是根据本发明的富勒烯水溶液粒径分布图。
图4是根据本发明的富勒烯水溶液清除羟基自由基图
具体实施方式
下面结合附图，对本发明的具体实施方式进行详细描述，但应当理解本发明的保护范围并不受具体实施方式的限制。
除非另有其它明确表示，否则在整个说明书和权利要求书中，术语“包括”或其变换如“包含”或“包括有”等等将被理解为包括所陈述的元件或组成部分，而并未排除其它元件或其它组成部分。
实施例1：本发明制备富勒烯水溶液
称取300mg富勒烯C60，分散于300g HS-15中，充分搅拌均匀，然后将混合物置于球磨机中球磨24h，转速700转/分钟，球磨机温度在35-45度之间，然后将混合物均质4次，压力40MPa。最后过滤得到澄清溶液。该富勒烯C60-HS15溶液中加入注射用水，得注射剂，粒径为50nm见图3。
实施例2：本发明制备富勒烯水溶液
称取10mg富勒烯C82，分散于300g HS-15中，充分搅拌均匀，然后将混合物置于球磨机中球磨24h，转速700转/分钟，球磨机温度在35-45度之间，然后将混合物均质4次，压力40MPa。最后过滤得到澄清溶液。
实施例3：本发明制备富勒烯水溶液
称取100mg富勒烯C60，分散于600mg HS-15中，充分搅拌均匀，然后将混合物置于球磨机中球磨24h，转速700转/分钟，球磨机温度在35-45度之间，然后将混合物均质4次，压力40MPa。最后过滤得到澄清溶液。
实施例4：本发明制备富勒烯水溶液
称取100mg富勒烯C84，分散于4000mg HS-15中，充分搅拌均匀，然后将混合物置于球磨机中球磨24h，转速700转/分钟，球磨机温度在35-45度之间，然后将混合物均质4次，压力40MPa。最后过滤得到澄清溶液。
实施例5：本发明制备富勒烯水溶液
称取100mg富勒烯C76，分散于400mg HS-15中，充分搅拌均匀，然后将混合物置于球磨机中球磨24h，转速700转/分钟，球磨机温度在35-45度之间，然后将混合物均质5次，压力40MPa。最后过滤得到澄清溶液。
实施例6：本发明制备富勒烯水溶液
称取500mg富勒烯C60，分散于600mg HS-15中，充分搅拌均匀，然后将混合物置于球磨机中球磨24h，转速700转/分钟，球磨机温度在35-45度之间，然后将混合物均质7次，压力40MPa。最后过滤得到澄清溶液。
实施例7：本发明制备富勒烯注射剂
取实施例1-6任意一项富勒烯水溶液30％，注射用水70％。
实施例8：本发明制备富勒烯注射剂
取实施例1-6任意一项富勒烯水溶液70％，注射用水30％。
实施例9：本发明制备富勒烯注射剂
取实施例1-6任意一项富勒烯水溶液50％，注射用水35％，无水乙醇15％。
实施例10：本发明制备富勒烯注射剂
取实施例1-6任意一项富勒烯水溶液42％，注射用水38％，无水乙醇10％。
实施例11：本发明制备富勒烯注射剂
取实施例1-6任意一项富勒烯水溶液65％，注射用水30％，无水乙醇5％。
实施例13：本发明制备富勒烯注射剂
取实施例1-6任意一项富勒烯水溶液67％，注射用水25％，无水乙醇8％。
前述对本发明的具体示例性实施方案的描述是为了说明和例证的目的。这些描述并非想将本发明限定为所公开的精确形式，并且很显然，根据上述教导，可以进行很多改变和变化。对示例性实施例进行选择和描述的目的在于解释本发明的特定原理及其实际应用，从而使得本领域的技术人员能够实现并利用本发明的各种不同的示例性实施方案以及各种不同的选择和改变。本发明的范围意在由权利要求书及其等同形式所限定。
Claims (2)
1.一种注射剂，其特征在于，所述注射剂通过下述制备方法得到：称取300mg富勒烯C60，分散于300g HS-15中，充分搅拌均匀，然后将混合物置于球磨机中球磨24h，转速700转/分钟，球磨机温度在35-45度之间，然后将混合物均质4次，压力40MPa，最后过滤得到澄清溶液；所述澄清溶液中加入注射用水，即得所述注射剂，粒径为50nm。
2.如权利要求1所述的注射剂在制备治疗肿瘤、帕金森病、骨髓抑制剂药物中的应用或清除体内自由基抗衰老药物中的应用。
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