CN113230416A - 一种石墨炔纳米制剂及其制备方法与在制备治疗帕金森病药物中的应用 - Google Patents
一种石墨炔纳米制剂及其制备方法与在制备治疗帕金森病药物中的应用 Download PDFInfo
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Abstract
本发明公开了一种石墨炔纳米制剂及其制备方法与在制备治疗帕金森病药物中的应用。所述石墨炔纳米制剂包括表面修饰有聚乙二醇的石墨炔纳米片以及二甲胺四环素。所述石墨炔纳米片具有较高的比表面积,且表面呈负电性,易于实现对药物的负载。此外,石墨炔纳米片具有较高的光热转换能力,可在近红外光照下产热,从而增加血脑屏障的渗透性,且该纳米递药系统具有光控释能力,可提高具有神经保护作用的二甲胺四环素的脑部递送效率,改善其抗帕金森病疗效。
Description
技术领域
本发明属于医药材料应用领域,具体涉及一种石墨炔纳米制剂及其制备方法与在制备治疗帕金森病药物中的应用。
背景技术
神经退行性疾病为人类健康带来了巨大威胁,其中,帕金森病作为第二大神经退行性疾病,随着人口的老龄化,其发病率也将进一步升高,然而,目前临床中却缺少有效的治疗方法,迫切需要研发新型抗帕金森病药物。而由于血脑屏障的存在,药物分子难以顺利进入脑部,到达病灶区域,这为抗帕金森病药物的研发带来了巨大的挑战。
纳米技术应用于帕金森病药物的研发有益于增加药物分子的跨血脑屏障能力,具有广阔的前景及应用价值。近年来的研究表明,短暂地提升脑部温度可安全、无伤、可逆地增加血脑屏障的渗透性,而许多纳米材料都具备光热转换能力,在近红外光照射(NIR)下都可产热,同时,这些纳米材料还具备药物负载能力,因此,以具有光热转换能力的纳米材料负载药物注入体内,并对脑部施加近红外光照,可安全、高效地实现药物的跨血脑屏障递送。
碳基二维纳米材料GDY具备比表面积大、π-π共轭、表面呈负电荷等特征,这些特点使其具有较强的药物负载能力,此外GDY还具备较高的光热转换能力,因此,有望实现药物的高效跨血脑屏障递送。
发明内容
本发明的第一目的在于,提供一种石墨炔纳米制剂的制备方法。
本发明的第二目的在于,提供通过上述石墨炔纳米制剂的制备方法得到的石墨炔纳米制剂。
本发明的第三目的在于,提供上述石墨炔纳米制剂在制备治疗帕金森病药物中的应用。
为实现上述目的,本发明采取的技术方案为:
一种石墨炔纳米制剂的制备方法,包括如下步骤:
S1、PEG-GDY的制备:
(1)向GDY水溶液中加入两端分别连接甲基与氨基的聚乙二醇(PEG)水溶液,搅拌状态下反应;
(2)所得反应产物离心处理,以水洗涤沉淀并重悬,即得PEG-GDY溶液;
S2、MN-PEG-GDY的制备:
(1)向PEG-GDY溶液中投入MN水溶液,避光搅拌状态下反应;
(2)所得反应产物离心处理,即得MN-PEG-GDY。
上述方法中,MN是指二甲胺四环素,GDY是指石墨炔纳米片,PEG-GDY是指表面修饰有聚乙二醇的石墨炔纳米片,MN-PEG-GDY是指负载有二甲胺四环素的石墨炔纳米制剂。
步骤S1中,所述的GDY优选粒径为80-120nm、厚度为5-6nm的GDY;更优选为通过如下方法制备得到的GDY:将石墨炔水溶液8-12℃下超声处理40-50h,超声产物10000-15000rpm离心4-6min,即得GDY;最优选为通过如下方法制备得到的GDY:将石墨炔水溶液10℃下超声处理48h,超声产物12000rpm离心5min,即得GDY。
所述的石墨炔优选通过如下方法制备得到:
(1)43.6mg六[(三甲基硅烷基)乙炔基]苯与15mL含有0.4mmol四丁基氟化铵的四氢呋喃在8℃下搅拌反应10min;
(2)向反应产物中加入10mL乙酸乙酯,并以卤水洗涤反应产物,随后加入20g无水硫酸钠除水;
(3)真空干燥(2)所得产物,并将干燥产物按每10mg产物对应25mL吡啶的比例分散于吡啶中,随后将所得溶液缓慢加入充满氮气的铜箔中,搅拌反应2天;
(4)以丙酮与二甲基甲酰胺反复洗涤铜箔;
(5)剥离铜箔表面薄膜,并依次在80℃的2M氢氧化钠、2M盐酸、2M氢氧化钠中过夜回流,即获得所述的石墨炔。
步骤S1中,所述的聚乙二醇的分子量优选为2000~4000Da。
步骤S1中,所述的GDY水溶液优选浓度为0.5-2mg/mL的GDY水溶液。
步骤S1中,所述的聚乙二醇水溶液优选浓度为0.5-2mg/mL的聚乙二醇水溶液。
步骤S1中,所述的GDY水溶液和聚乙二醇水溶液的配比,优选为体积比1:1-3;更优选为1:2。
步骤S1中,所述的离心处理的条件优选为转速10000-15000rpm离心4-6min;更优选为转速12000rpm离心5min。
步骤S2中,所述的PEG-GDY溶液优选浓度为0.5-2mg/mL的PEG-GDY溶液;更优选浓度为1mg/mL的PEG-GDY溶液。
步骤S2中,所述的MN水溶液优选浓度为0.5-2mg/mL的MN水溶液;更优选浓度为1mg/mL的MN水溶液。
步骤S2中,所述的PEG-GDY溶液和MN水溶液的配比,优选为体积比1:0.5-3;更优选为1:1。
一种石墨炔纳米制剂,通过上述制备方法制备得到。
上述石墨炔纳米制剂在制备治疗治疗帕金森病药物中的应用。
上述石墨炔纳米制剂在制备逆转多巴胺能神经元丢失药物中的应用。
所述的多巴胺能神经元丢失是MPTP诱导形成的症状。
所述的应用中,所述药物的剂型优选为注射剂。所述药物MN-PEG-GDY通过可静脉注射到体内。
使用过程中,可以H2O对MN-PEG-GDY进行稀释。
上述应用中,所述药物的用量以MN定量,按每kg给药对象施加MN的剂量为2-4mg计,更优选为3mg/kg计。
相比于现有技术,本发明的有益效果为:
(1)提供了一种GDY纳米制剂的制备方法。MN对帕金森病具有治疗作用,且其分子结构中具有氨基基团,在水中易发生质子化反应,使其具备正电性,因此易于被表面呈负电性的GDY负载,共同构成可高效治疗帕金森病的纳米制剂。
(2)GDY较大的比表面积、π-π共轭及表面具有负电荷的特点,使其相比于传统纳米制剂具有更高的药物负载能力。
(3)GDY的光热效应可安全、无伤、可逆地增加血脑屏障的渗透性,改善脑部递药效率。
(4)MN-PEG-GDY具有光控释能力,可提高具有神经保护作用的二甲胺四环素的脑部递送效率,改善其抗帕金森病疗效。
(5)GDY或PEG-GDY的浓度到达50μg/mL,SH-Sy5y细胞的存活率仍大于80%;MN-PEG-GDY+NIR组小鼠的血常规、肝功、肾功均在正常范围内;本发明MN-PEG-GDY+NIR策略的安全性高。
附图说明
图1为本发明实例1制备的GDY的表征结果图;其中,A为GDY的粒径分布,B为GDY与PEG-GDY的Zeta电势,C为GDY的透射电镜成像,D为GDY的原子力显微镜成像及其厚度分析,E、F为GDY的为能量色散X射线能谱图,G为PEG-GDY的拉曼图谱,H为PEG-GDY在水与血清中的稳定性。
图2为本发明实例2对PEG-GDY光热行为检测结果图;其中,A为PEG-GDY在不同介质中的成像,B为梯度浓度的PEG-GDY经NIR照射后的升温行为,C为125μg/mL的PEG-GDY经1W/cm2NIR照射5min时的温度改变,D为125μg/mL的PEG-GDY的光热转换效率,E为PEG-GDY的光热稳定性考察。
图3为本发明实例3制备的MN-PEG-GDY的表征结果图;其中,A为MN在365nm处的吸光度-浓度标准曲线,B为PEG-GDY对MN的载药率,C为PEG-GDY对MN的载药量,D为MN-PEG-GDY的释药行为。
图4为实施实例4中PEG-GDY作为药物载体的体外评价结果图;其中,A为PEG-GDY对SH-Sy5y细胞的毒性评价,B为不同时间下SH-Sy5y细胞对Cy7-PEG-GDY的摄取成像,C为不同时间下SH-Sy5y细胞对Cy7-PEG-GDY的摄取量,D为SH-Sy5y对不同浓度的Cy7-PEG-GDY的摄取量。
图5为实施实例5中PEG-GDY作为药物载体的跨血脑屏障评价结果图;其中,A为Cy7-PEG-GDY在NIR下的血脑屏障渗透率,B为经近红外光照后,bEnd.3细胞的跨内皮电阻。
图6为实施实例6中Cy7-PEG-GDY在体内各脏器的分布图。
图7为实施实例7中MN-PEG-GDY对PD模型小鼠的行为学影响结果图;其中,A、B为爬杆实验结果,C、D为转棒实验结果,E、G为旷场实验结果。
图8为实施实例7中,MN-PEG-GDY对PD模型小鼠脑部的TH阳性神经元存活率及多巴胺及其代谢物的影响结果图;其中,A、B为TH阳性神经元的免疫荧光成像及其定量分析,C-E为纹状体中多巴胺及其代谢产物的定量分析。
图9为实施实例8中,对MN-PEG-GDY的安全性评价结果图;其中,A为对小鼠各脏器的H&E染色,B为对小鼠的血常规检测,C为对小鼠的肝功、肾功检测。
图10为本发明石墨炔纳米制剂的制备及其突破血脑屏障递送药物示意图。
具体实施方式
下面结合实施例及附图对本发明作进一步详细的描述,但本发明的实施方式不限于此。
除非另有定义,本发明中所使用的所有科学和技术术语具有与本发明涉及技术领域的技术人员通常理解的相同的含义。
为了对本发明的技术特征、目的和有益效果有更加清楚的理解,现对本发明的技术方案进行以下详细说明,但不能理解为对本发明的可实施范围的限定。
实施例1
本发明的一种实施例,本实施例提供一种GDY及PEG-GDY的制备方法,其制备方法为:
(1)石墨炔制备:
43.6mg六[(三甲基硅烷基)乙炔基]苯与15mL含有0.4mmol四丁基氟化铵的四氢呋喃溶液在8℃下搅拌反应10min,随后加入10mL乙酸乙酯,以卤水洗涤反应产物,并加入20g无水硫酸钠干燥。随后,将所得产物在真空条件下室温干燥至溶剂挥发完全,并按每10mg产物对应25mL吡啶的比例分散于吡啶中,所得溶液缓慢加入充满氮气的铜箔中,搅拌反应2天,此时,铜箔表面将出现石墨炔薄膜。随后用10mL丙酮和10mL二甲基甲酰胺洗涤铜箔,并将石墨炔薄膜从铜箔上剥离,依次在80℃的2M氢氧化钠、2M盐酸、2M氢氧化钠中过夜回流反应。将所得石墨炔固体离心后10mL水重悬,并用超纯水和丙酮依次洗涤(每次10mL),最后室温真空浓缩待用。
(2)GDY制备
将所得石墨炔按1mg石墨炔与1mL水混合后,在10℃条件下300W超声破碎48h,随后将产物以12000rpm转速离心5min,所得产物即为GDY,重悬于水中,待用。
(3)PEG-GDY制备
取1mL GDY水溶液(1mg/mL)加入2mL两端分别连接甲基与氨基的聚乙二醇(PEG,分子量为2000Da)溶液(1mg/mL),过夜(8-16h)搅拌,随后,将反应产物在12000rpm转速下离心5min,以水洗涤反应产物并重悬于水中,即得PEG-GDY溶液。
由图1可见,PEG-GDY的平均粒径约为100nm,厚度为5-6nm,Zeta电势为-17.4mV。由X射线光电子能谱可见,284.0eV处的特征峰为碳原子的1s轨道,283.6eV与284.2eV处的特征峰表明体系存在sp2与sp杂化轨道,说明该体系中存在碳碳双键与碳碳单键,此外,286.0eV处的峰表明PEG-GDY体系存在轻微的被氧化。拉曼光谱中,1366,1574及1900-2200cm-1处的峰表明所合成的PEG-GDY的成功合成。此外,将PEG-GDY在37℃条件下分别保存于水与FBS中一周,其粒径未发生较大改变,说明PEG-GDY在水与FBS中的稳定性良好。
实施例2
本发明的一种实施例,本实施例提供一种PEG-GDY的光热行为。配制梯度浓度的PEG-GDY溶液(15.6μg/mL,31.3μg/mL,62.5μg/mL,125μg/mL)。将梯度浓度的PEG-GDY溶液分别置于透明的石英皿中,以1W/cm2强度的808nm近红外光照射5min,并分别记录其温度变化,此外,其光热转换系数约为32%,计算公式如下:
η=(hA△Tmax–Q)/I(1-10-Aλ)
式中,η为光热转换效率,h是分散的光热的传热系数,A是容器的表面积,△Tmax是近红外光照下的最大温度提升,I为光照强度,-A808为PEG-GDY在近红外光照射下的吸光度,Q是纯分散液体吸收的热量。
如图2E所示,PEG-GDY在经5次近红外光照(光照条件同上)后,其光热行为并未发生较大变化,因此,PEG-GDY具有较好的光热稳定性。
实施例3
本发明的一种实施例,本实施例提供一种PEG-GDY负载MN的方法。首先配制不同比例MN水溶液(3.91μg/mL,7.81μg/mL,15.6μg/mL,31.3μg/mL,62.5μg/mL),以紫外可见光分光光度计分别测定365nm处的吸光度,绘制浓度-吸光度标准曲线。取1mg浓度为1mg/mL的PEG-GDY水溶液浓度为1mg/mL,按PEG-GDY水溶液与MN水溶液的体积比分别为1:0.5、1:1、1:2、1:3加入浓度1mg/mL的MN水溶液,过夜搅拌,并以12000rpm的转速离心5min,即得MN-PEG-GDY,并测定上清液中MN含量,计算载药率与载药量。由图3B和3C所示,MN的载药率随投料比的增加而减小,而载药量则随投料比的增加而增大,优选地,选择投料比为1:1制备MN-PEG-GDY。
将所得MN-PEG-GDY分别溶于37℃水与PBS中,并分别对比其在有无近红外光照(808nm,1W/cm2)下的药物释放行为,并在结束光照后以12000rpm转速离心5min,测定上清液中的MN含量,以此计算MN的释药量。如图3D所示,近红外光照可促进MN-PEG-GDY的释药行为。
实施例4
本发明的一种实施例,本实施例提供一种GDY或PEG-GDY的细胞毒性作用及SH-Sy5y细胞(ATCC)对其的摄取行为。
细胞毒性作用
将SH-Sy5y细胞以5000/室的浓度接种于96孔板中,并分别以0,1,2,5,10,20,50,100μg/mL浓度的GDY或PEG-GDY孵化细胞,24h后,加入10μL CCK-8试剂,在37℃下孵化2h,随后以酶标仪测定培养液在450nm下的的吸光度。并以以下公式计算细胞存活率:
细胞存活率=(Acell-Ablank)/(A0-Ablank)×100%
其中,Acell为包含GDY或PEG-GDY的培养液在450nm处的吸光度,A0为正常培养液在450nm处的吸光度,Ablank为空白对照。
如图4A所示,即便GDY或PEG-GDY的浓度到达50μg/mL,SH-Sy5y细胞的存活率仍大于80%,说明该纳米载体的安全性较高。
细胞摄取作用
以Cy7标记的PEG-GDY孵化SH-Sy5y细胞,分别在1,2,4h时以含有DAPI的多聚甲醛固定细胞,并以共聚焦显微镜成像。此外,以流式测定SH-Sy5y细胞对不同浓度Cy7-PEG-GDY(0,10,20,30,40,50,100μg/mL)及20μg/mL的Cy7-PEG-GDY在不同时间点(0,0.5,1,2,3,6,9,12h)的摄取量。Cy7-PEG-GDY制备方法如下:1mL GDY溶液(1mg/mL)加入2mL一端接有氨基的Cy7-PEG(1mg/mL)溶液中,避光过夜搅拌,随后以12000rpm转速离心5min,离心产物重悬于水中,即得。
如图4B-图4D所示,即便在10μg/mL浓度下,SH-Sy5y细胞依然对Cy7-PEG-GDY存在较高的摄取量,而随着Cy7-PEG-GDY浓度的升高,SH-Sy5y细胞对其的摄取量趋于饱和。
实施例5
本发明的一种实施例,本实施例说明由GDY介导的光热作用可有效地在体外模型中增加血脑屏障渗透性。以bEnd.3细胞(ATCC)接种于Transwell中建立体外血脑屏障模型,当跨膜电阻达到200Ω·cm2时视为血脑屏障模型完成。将10μg的Cy7-PEG或Cy7-PEG-GDY加入上室孵化4h,并对Cy-PEG-GDY组施加强度为1W/cm2的NIR 5min(808nm),随后,分别以紫外可见光分光光度计测定上室在756nm处的吸光度,并以以下公式计算渗透率:
渗透率(%)=(C0-Cs)/C0×100%
其中,C0与Cs分别为孵化前后Cy7在上室中的浓度。
如图5所示,Cy7-PEG-GDY组在施加NIR后显著增加了Cy7的渗透率,且bEnd.3细胞层的膜电位在光照前后并无显著改变,说明由GDY介导的光热效应可安全、有效地增加血脑屏障的渗透性。
实施例6
本发明的一种实施例,本实施例提供一种PEG-GDY纳米载体在体内的分布。所用小鼠为C57BL/6,将小鼠分无NIR组与NIR组。向小鼠尾静脉注射Cy7-PEG-GDY,给药剂量为5mg/kg,给药6h后,脱颈处死小鼠,并取出其脑、心、肝、脾、肺、肾,检测其各脏器内的荧光强度。其中,光照组小鼠在尾静脉注射后30min,向其脑部施加NIR(808nm,1W/cm2,5min)。如图6所示,NIR组小鼠脑部的荧光聚集显著大于无光照组,说明由GDY介导的光热作用有助于增加血脑屏障的渗透性。
实施例7
本发明的一种实施例,本实施例提供一种MN-PEG-GDY纳米制剂的体内抗帕金森药效评价。将小鼠随机分为6组,分别为Control组、MPTP组、L-DOPA(左旋多巴)组、MN组、MN-PEG-GDY组、MN-PEG-GDY+NIR组,除Control组外,其余各组都进行帕金森病造模,造模方法为:每隔两小时向小鼠腹腔注射MPTP溶液,共注射四次,每次给药剂量为18mg/kg。造模完成后,各组分别接受不同治疗方式,治疗周期为8天,其中,L-DOPA组每隔两天尾静脉注射25mg/kg的L-DOPA溶液,MN组、MN-PEG-GDY组、MN-PEG-GDY+NIR组分别每隔两天尾静脉注射3mg/kg的MN溶液、MN-PEG-GDY溶液(以MN定量),其中,光照组在给药30min后施加808nm的NIR(1W/cm2,5min)。为评价药效,对各组小鼠进行行为学评价,分别为爬杆试验、转棒试验、旷场试验。爬杆试验所用杆为表面粗糙、直径为1cm,高度为50cm,分别记录小鼠扭头时间及爬至杆底时间。转棒试验所用转棒直径为7cm,转速设置为20r/min,记录小鼠在2min内的首次掉落时间及总共掉落次数。旷场试验所用旷场为60cm×60cm×40cm,测试时间为10min,记录活动总路程及平均速度。如图7所示,MN-PEG-GDY+NIR组的小鼠行为学评价与Control组及L-DOPA组相似。
取各组小鼠的脑组织进行冰冻切片,并对黑质区域进行免疫荧光,检测TH阳性神经元的数量。如图8A-8B所示,与MPTP组相比,MN-PEG-GDY+NIR组显著增加了TH阳性神经元的数量,与Control组及L-DOPA组相似,说明MN-PEG-GDY+NIR策略可有效改善由MPTP引起的神经毒性。此外,取纹状体,分别对其中的多巴胺及其代谢产物进行定量分析,结果如图8C-图8E所示,MN-PEG-GDY+NIR组同样展现出了良好的抗帕金森疗效。
实施例8
本发明的一种实施例,本实施例提供一种MN-PEG-GDY+NIR策略的安全性评价。取实施例7小鼠,解剖,分别取其心、肝、脾、肺、肾,对这些主要脏器进行H&E染色。如图9A所示,MN-PEG-GDY+NIR组小鼠的H&E染色并未观察到组织损伤现象。此外,对各组小鼠的血、肝、肾进行分析,如图9B-图9C所示,MN-PEG-GDY+NIR组小鼠的血常规、肝功、肾功均在正常范围内,说明MN-PEG-GDY+NIR策略的安全性较高。
上述实施例为本发明较佳的实施方式,但本发明的实施方式并不受上述实施例的限制,其他的任何未背离本发明的精神实质与原理下所作的改变、修饰、替代、组合、简化,均应为等效的置换方式,都包含在本发明的保护范围之内。
Claims (10)
1.一种石墨炔纳米制剂的制备方法,其特征在于:包括如下步骤:
S1、PEG-GDY的制备:
(1)向GDY水溶液中加入两端分别连接甲基与氨基的聚乙二醇水溶液,搅拌状态下反应;
(2)所得反应产物离心处理,以水洗涤沉淀并重悬,即得PEG-GDY溶液;
S2、MN-PEG-GDY的制备:
(1)向PEG-GDY溶液中投入MN水溶液,避光搅拌状态下反应;
(2)所得反应产物离心处理,即得MN-PEG-GDY;
其中,MN是指二甲胺四环素,GDY是指石墨炔纳米片,PEG-GDY是指表面修饰有聚乙二醇的石墨炔纳米片,MN-PEG-GDY是指负载有二甲胺四环素的石墨炔纳米制剂。
2.根据权利要求1所述的石墨炔纳米制剂的制备方法,其特征在于:
步骤S1中,所述的GDY选取粒径为80-120nm、厚度为5-6nm的GDY;通过如下方法制备得到:将石墨炔水溶液8-12℃下超声处理40-50h,超声产物10000-15000rpm离心4-6min,即得GDY。
3.根据权利要求1所述的石墨炔纳米制剂的制备方法,其特征在于:
步骤S1中,所述的聚乙二醇的分子量为2000~4000Da;
步骤S1中,所述的GDY水溶液是浓度为0.5-2mg/mL的GDY水溶液;
步骤S1中,所述的聚乙二醇水溶液是浓度为0.5-2mg/mL的聚乙二醇水溶液;
步骤S1中,所述的GDY水溶液和聚乙二醇水溶液的配比为体积比1:1-3;
步骤S1中,所述的离心处理的条件为转速10000-15000rpm离心4-6min;
步骤S2中,所述的PEG-GDY溶液是浓度为0.5-2mg/mL的PEG-GDY溶液;
步骤S2中,所述的MN水溶液是浓度为0.5-2mg/mL的MN水溶液;
步骤S2中,所述的PEG-GDY溶液和MN水溶液的配比为体积比1:0.5-3。
4.根据权利要求1所述的石墨炔纳米制剂的制备方法,其特征在于:
步骤S1中,所述的GDY水溶液和聚乙二醇水溶液的配比为体积比1:2;
步骤S1中,所述的离心处理的条件为转速12000rpm离心5min;
步骤S2中,所述的PEG-GDY溶液是浓度为1mg/mL的PEG-GDY溶液;
步骤S2中,所述的MN水溶液优是浓度为1mg/mL的水MN溶液;
步骤S2中,所述的PEG-GDY溶液和MN水溶液的配比为体积比为1:1。
5.根据权利要求1所述的石墨炔纳米制剂的制备方法,其特征在于:
所述的石墨炔通过如下方法制备得到:
(1)43.6mg六[(三甲基硅烷基)乙炔基]苯与15mL含有0.4mmol四丁基氟化铵的四氢呋喃在8℃下搅拌反应10min;
(2)向反应产物中加入10mL乙酸乙酯,并以卤水洗涤反应产物,随后加入20g无水硫酸钠除水;
(3)真空干燥(2)所得产物,并将干燥产物按每10mg产物对应25mL吡啶的比例分散于吡啶中,随后将所得溶液缓慢加入充满氮气的铜箔中,搅拌反应2天;
(4)以丙酮与二甲基甲酰胺反复洗涤铜箔;
(5)剥离铜箔表面薄膜,并依次在80℃的2M氢氧化钠、2M盐酸、2M氢氧化钠中过夜回流,即获得所述的石墨炔。
6.一种石墨炔纳米制剂,其特征在于:通过权利要求1-5任一项所述的方法制备得到。
7.权利要求6所述的石墨炔纳米制剂在制备治疗治疗帕金森病药物中的应用。
8.权利要求6所述的石墨炔纳米制剂在制备逆转多巴胺能神经元丢失药物中的应用。
9.根据权利要求8所述的应用,其特征在于:
所述的多巴胺能神经元丢失是MPTP诱导形成的症状。
10.根据权利要求8或9所述的应用,其特征在于:
所述药物的用量以MN定量,按每kg给药对象施加MN的剂量为2-4mg计。
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