CN111714453A - 一种抗菌胶束及其制备方法 - Google Patents
一种抗菌胶束及其制备方法 Download PDFInfo
- Publication number
- CN111714453A CN111714453A CN202010608997.4A CN202010608997A CN111714453A CN 111714453 A CN111714453 A CN 111714453A CN 202010608997 A CN202010608997 A CN 202010608997A CN 111714453 A CN111714453 A CN 111714453A
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- China
- Prior art keywords
- micelle
- antibacterial
- phenylalanine
- quaternary ammonium
- ammonium salt
- Prior art date
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Abstract
本发明涉及一种抗菌胶束及其制备方法,属于药物制剂技术领域。该抗菌胶束按重量百分比计,包括如下组份:L‑苯丙氨酸季铵盐8‑15%,余量为水,还可以包含活性成分0.1‑3%、皮肤外用制剂中可接受的辅料4‑22%。该抗菌胶束中含有L‑苯丙氨酸季铵盐,季铵盐基团使得L‑苯丙氨酸季铵盐带正电荷,通过静电引力,吸附于带负电荷的微生物细胞表面,在长烷基取代链的推动下,穿透细胞膜,并通过静电引力与细胞膜中的磷脂双分子层及其它负电物质结合,破坏细胞膜,引起内容物释放,最终微生物死亡,达到抗菌的目的。该抗菌胶束制备方法简单,易操作,且成本低,适合工业化生产。
Description
技术领域
本发明属于药物制剂技术领域,具体涉及一种抗菌胶束及其制备方法。
背景技术
聚合物胶束是由合成的两亲性嵌段共聚物在水中自由组装形成的一种热力学稳定的胶体溶液。其中,两亲性嵌段共聚物由疏水片段和亲水片段组成,并且亲水片段体积一般大于疏水片段,两亲性嵌段共聚物可以在水中自发形成核壳结构,疏水片段形成胶束内核,亲水片段形成胶束外壳。由于这种独特的化学结构,在水溶液中能够形成具有球形的内核-外壳结构的共聚物胶束,其内核作为疏水性药物的容器,将药物增溶在内部,降低其毒副作用,外壳则对药物起保护作用,提高药物的稳定性,并且达到缓释作用,同时通过胶束的表面修饰可以达到靶向作用。
细菌感染对人类健康构成了严重威胁,而传统抗生素治疗可能导致如胃病等一系列副作用,并且抗生药物的滥用将导致耐药菌的出现。因此,亟需发展提高抗生素抗菌效率的新方法。而胶束具有很好的耐药性,并且可以通过靶向性,精准病灶部位给药,不会对其他部位产生不良作用,除此之外,还能减少药物用量。目前越来越多研究旨在胶束上含有的抗菌多肽链段能够有效杀死细菌,在很大程度上提高胶束的抗菌效率。
发明内容
有鉴于此,本发明的目的之一在于提供一种抗菌胶束;目的之二在于提供一种抗菌胶束的制备方法。
为达到上述目的,本发明提供如下技术方案:
1、一种抗菌胶束,按重量百分比计,所述抗菌胶束包括如下组份:L-苯丙氨酸季铵盐8-15%,余量为水。
优选的,按重量百分比计,所述抗菌胶束还包括活性成分0.1-3%。
优选的,所述活性成分包括依沙吖啶、依托度酸、酮洛芬、普拉洛芬、氟比洛芬、美洛昔康、阿克他利、舒林酸、塞来昔布、噻洛芬酸、替诺昔康、萘普生、吡罗昔康、联苯乙酸、阿西美辛、安吡昔康、氨芬酸、布洛芬、扎托洛芬、双氯芬酸、吲哚美辛、莫苯唑酸、洛索洛芬、氯苯扎利或氯诺昔康中的至少一种。
优选的,按重量百分比计,所述抗菌胶束还包括皮肤外用制剂中可接受的辅料4-22%。
优选的,所述辅料包括保湿剂、增稠剂和防腐剂;所述保湿剂占所述抗菌胶束总重量的3-10%,所述增稠剂占所述抗菌胶束总重量的0.1-2%,所述防腐剂占所述抗菌胶束总重量的1-10%。
优选的,所述保湿剂为1,3-丁二醇、1,3-丙二醇、乳酸钠、甘油、羟乙基脲、透明质酸钠、甲壳素、甲壳素衍生物或植物多糖提取物中的至少一种;所述增稠剂为聚丙烯酸酯交联聚合物-6、丙烯酸羟乙酯/丙烯酰二甲基牛磺酸钠共聚物、聚丙烯酸钠、聚丙烯酸类聚合物、黄原胶或羟乙基纤维素中的至少一种;所述防腐剂为苯氧基乙醇、对羟基苯甲酸甲酯、对羟基苯甲酸丙酯或山梨醇中的至少一种。
优选的,所述L-苯丙氨酸季铵盐按如下方法制备:
(1)在-4-0℃下,将L-苯丙氨酸溶于辛醇、十四醇或十六醇中,然后滴入二氯亚砜,于25-28℃下以200-500rpm的速度搅拌反应2-3d后固液分离,将获得的固相物质I用乙醚洗涤,制得L-苯丙氨酸酯盐,所述L-苯丙氨酸溶于辛醇、二氯亚砜与辛醇、十四醇或十六醇的质量体积比为0.5-2:1-2:10-15,g:mL:mL;
(2)将步骤(1)中制得的L-苯丙氨酸酯盐和碳酸钾溶解于乙腈中,再加入溴乙烷,混匀后升温至90-95℃后以200-500rpm的速度搅拌反应12-24h,然后去除过量的碳酸钾和乙腈后固液分离,将获得的固相物质II用乙醚洗涤,制得L-苯丙氨酸季铵盐,所述L-苯丙氨酸酯盐、碳酸钾、乙腈与溴乙烷的质量体积比为1-3:1-1.5:10-20:4-6。
优选地,步骤(1)和步骤(2)中,所述乙醚洗涤的次数均为3-5次。
2、所述的一种抗菌胶束的制备方法,所述方法如下:
A、将皮肤外用制剂中可接受的辅料溶于PBS缓冲液中,获得溶液I;
B、将L-苯丙氨酸季铵盐和活性成分加入二氯甲烷和甲醇的混合液中,混匀后旋转蒸发至所述混合液挥发,形成一层透明薄膜,再加入步骤A中的溶液I,超声至所述透明薄膜溶解,以100-300rpm的速度搅拌6-12h,过滤后得固相物质III,将所述固相物质III冷冻干燥后溶于水,即可。
优选的,步骤A中,所述PBS缓冲液的浓度为0.01mol/L,pH=7.4。
优选的,步骤B中,所述二氯甲烷和甲醇的体积比为3-5:1。
优选的,步骤B中,所述混匀后旋转蒸发具体为:混匀后于40-50℃下以100-200rpm的速度旋转蒸发。
优选的,步骤B中,所述冷冻干燥后溶于水具体为:对冷冻干燥后的产物中各组分含量进行测试,然后根据对抗菌胶束中各组分含量的实际需求设定所述产物和水的用量,将所述产物溶于水,即可。
本发明的有益效果在于:本发明提供了一种抗菌胶束及其制备方法,该抗菌胶束中含有L-苯丙氨酸季铵盐,季铵盐基团使得L-苯丙氨酸季铵盐带正电荷,通过静电引力,吸附于带负电荷的微生物细胞表面,在长烷基取代链的推动下,穿透细胞膜,并通过静电引力与细胞膜中的磷脂双分子层及其它负电物质结合,破坏细胞膜,引起内容物释放,最终微生物死亡,达到抗菌的目的。L-苯丙氨酸季铵盐中除了季铵盐基团发挥抗菌作用外,其含有的长链烷基能够进一步提升其抗菌作用,因为长链烷基能够增加季铵盐基团的疏水性作用,从而增强其对细胞膜稳定性的破坏作用,提升其对细胞膜的溶解能力,而这样又能进一步导致细胞膜中产生更大的自由体积,更大的自由体积又能够容纳更长的长链烷基,如此,不断的增强季铵盐基团的抗菌作用。在制备该抗菌胶束过程中,将溶液I与透明薄膜混合,通过控制搅拌转速和时间,最终可以形成大小均匀的抗菌胶束。该抗菌胶束制备方法简单,易操作,且成本低,适合工业化生产。
本发明的其他优点、目标和特征在某种程度上将在随后的说明书中进行阐述,并且在某种程度上,基于对下文的考察研究对本领域技术人员而言将是显而易见的,或者可以从本发明的实践中得到教导。本发明的目标和其他优点可以通过下面的说明书来实现和获得。
附图说明
为了使本发明的目的、技术方案和优点更加清楚,下面将结合附图对本发明作优选的详细描述,其中:
图1为在4℃冷藏避光条件下,7天内对比实施例1中空白胶束和实施例1中抗菌胶束粒径变化结果图;
图2为在4℃冷藏避光条件下,7天内实施例1中抗菌胶束中活性物质含量的变化结果图;
图3为实施例1至实施例3中抗菌胶束的体外释放性能测试结果图。
具体实施方式
以下通过特定的具体实例说明本发明的实施方式,本领域技术人员可由本说明书所揭露的内容轻易地了解本发明的其他优点与功效。本发明还可以通过另外不同的具体实施方式加以实施或应用,本说明书中的各项细节也可以基于不同观点与应用,在没有背离本发明的精神下进行各种修饰或改变。
实施例1
一种抗菌胶束,按重量百分比计,该抗菌胶束包括如下组份:L-苯丙氨酸季铵盐10%,活性成分(氯苯扎利)1%,皮肤外用制剂中可接受的辅料(保湿剂[1,3-丁二醇]5%、增稠剂[黄原胶]0.1%、防腐剂[对羟基苯甲酸丙酯]1%)6.1%,余量为纯化水。该抗菌胶束按如下方法制备:
(1)在-4℃下,将L-苯丙氨酸溶于十四醇中,然后滴入二氯亚砜,于25℃下以200rpm的速度搅拌反应3d后固液分离,将获得的固相物质I用乙醚洗涤4次,制得L-苯丙氨酸十四酯盐,其中,L-苯丙氨酸、二氯亚砜与十四醇的质量体积比为0.5:1.5:10,g:mL:mL;
(2)将步骤(1)中制得的L-苯丙氨酸十四酯盐和碳酸钾溶解于乙腈中,再加入溴乙烷,混匀后升温至90℃后以200rpm的速度搅拌反应24h,然后去除过量的碳酸钾和乙腈后固液分离,将获得的固相物质II用乙醚洗涤4次,制得L-苯丙氨酸季铵盐,其中,L-苯丙氨酸十四酯盐、碳酸钾、乙腈与溴乙烷的质量体积比为1:1.5:20:6;
(3)将皮肤外用制剂中可接受的辅料(保湿剂[1,3-丁二醇]、增稠剂[黄原胶]、防腐剂[对羟基苯甲酸丙酯])溶于浓度为0.01mol/L,pH=7.4的PBS缓冲液中,获得溶液I;
(4)将步骤(2)中制得L-苯丙氨酸季铵盐和活性成分(氯苯扎利)加入二氯甲烷和甲醇按体积比3:1混合而成的混合液中,混匀后于40℃下以100rpm的速度旋转蒸发至该混合液挥发,形成一层透明薄膜,再加入步骤(3)中的溶液I,超声至透明薄膜溶解,以200rpm的速度搅10h,过滤后得固相物质III,将固相物质III冷冻干燥后,对冷冻干燥后的产物中各组分含量进行测试,然后根据该抗菌胶束中各组分的重量百分比设定该产物和纯化水的用量,将该产物溶于纯化水,即可。
实施例2
一种抗菌胶束,按重量百分比计,该抗菌胶束包括如下组份:L-苯丙氨酸季铵盐8%,活性成分(普拉洛芬)3%,皮肤外用制剂中可接受的辅料(保湿剂[透明质酸钠]3%、增稠剂[聚丙烯酸钠]1%、防腐剂[苯氧基乙醇]2%)6%,余量为纯化水。该抗菌胶束按如下方法制备:
(1)在-2℃下,将L-苯丙氨酸溶于辛醇中,然后滴入二氯亚砜,于25℃下以400rpm的速度搅拌反应2d后固液分离,将获得的固相物质I用乙醚洗涤5次,制得L-苯丙氨酸辛酯盐,其中,L-苯丙氨酸、二氯亚砜与辛醇的质量体积比为2:1:12,g:mL:mL;
(2)将步骤(1)中制得的L-苯丙氨酸辛酯盐和碳酸钾溶解于乙腈中,再加入溴乙烷,混匀后升温至95℃后以500rpm的速度搅拌反应12h,然后去除过量的碳酸钾和乙腈后固液分离,将获得的固相物质II用乙醚洗涤5次,制得L-苯丙氨酸季铵盐,其中,L-苯丙氨酸辛酯盐、碳酸钾、乙腈与溴乙烷的质量体积比为3:1:10:4;
(3)将皮肤外用制剂中可接受的辅料(保湿剂[透明质酸钠]、增稠剂[聚丙烯酸钠]、防腐剂[苯氧基乙醇])溶于浓度为0.01mol/L,pH=7.4的PBS缓冲液中,获得溶液I;
(4)将步骤(2)中制得L-苯丙氨酸季铵盐和活性成分(普拉洛芬)加入二氯甲烷和甲醇按体积比4:1混合而成的混合液中,混匀后于60℃下以100rpm的速度旋转蒸发至该混合液挥发,形成一层透明薄膜,再加入步骤(3)中的溶液I,超声至透明薄膜溶解,以100rpm的速度搅12h,过滤后得固相物质III,将固相物质III冷冻干燥后,对冷冻干燥后的产物中各组分含量进行测试,然后根据该抗菌胶束中各组分的重量百分比设定该产物和纯化水的用量,将该产物溶于纯化水,即可。
实施例3
一种抗菌胶束,按重量百分比计,该抗菌胶束包括如下组份:L-苯丙氨酸季铵盐15%,活性成分(布洛芬)0.1%,皮肤外用制剂中可接受的辅料(保湿剂[甘油]10%、增稠剂[羟乙基纤维素]2%、防腐剂[山梨醇]1%)13%,余量为纯化水。该抗菌胶束按如下方法制备:
(1)在0℃下,将L-苯丙氨酸溶于十六醇中,然后滴入二氯亚砜,于28℃下以500rpm的速度搅拌反应2d后固液分离,将获得的固相物质I用乙醚洗涤3次,制得L-苯丙氨酸十六酯盐,其中,L-苯丙氨酸、二氯亚砜与十六醇的质量体积比为2:2:10,g:mL:mL;
(2)将步骤(1)中制得的L-苯丙氨酸十六酯盐和碳酸钾溶解于乙腈中,再加入溴乙烷,混匀后升温至90℃后以300rpm的速度搅拌反应18h,然后去除过量的碳酸钾和乙腈后固液分离,将获得的固相物质II用乙醚洗涤3次,制得L-苯丙氨酸季铵盐,其中,L-苯丙氨酸十六酯盐、碳酸钾、乙腈与溴乙烷的质量体积比为2:1:15:5;
(3)将皮肤外用制剂中可接受的辅料(保湿剂[甘油]、增稠剂[羟乙基纤维素]、防腐剂[山梨醇])溶于浓度为0.01mol/L,pH=7.4的PBS缓冲液中,获得溶液I;
(4)将步骤(2)中制得L-苯丙氨酸季铵盐和活性成分(布洛芬)加入二氯甲烷和甲醇按体积比5:1混合而成的混合液中,混匀后于50℃下以200rpm的速度旋转蒸发至该混合液挥发,形成一层透明薄膜,再加入步骤(3)中的溶液I,超声至透明薄膜溶解,以300rpm的速度搅6h,过滤后得固相物质III,将固相物质III冷冻干燥后,对冷冻干燥后的产物中各组分含量进行测试,然后根据该抗菌胶束中各组分的重量百分比设定该产物和纯化水的用量,将该产物溶于纯化水,即可。
对比实施例1
与实施例1的区别在于,不含有活性物质(氯苯扎利),即为空白胶束。
对比实施例2
与实施例1的区别在于,不包含步骤(1)和步骤(2),以L-苯丙氨酸替换L-苯丙氨酸季铵盐制备胶束。
实施例4
包封率和载药量测定
将实施例1至实施例3中抗菌胶束及对比实施例2中胶束冻干后,分别用DMSO复溶,均采用紫外可见分光光度法测定各抗菌胶束中活性物质的吸光度,代入对应活性物质的标准曲线回归方程中计算相应活性物质的含量,并按照下列公式计算包封率(encapsulationefficacy,EE)和载药量(loading capacity,LC):
结果如表1所示。
表1包封率和载药量测试结果
由表1可知,实施例1至实施例3中抗菌胶束较对比实施例2中胶束具有较好的包封率和载药量。
实施例5
胶束粒径及电位测定
将实施例1至实施例3中抗菌胶束及对比实施例1中胶束分别置于比色皿中,利用纳米粒度及电位分析仪测定各胶束的粒径、粒径分散系数(PDI)和Zeta电位,温度设定为室温25℃,测试角度为90°,测试结果见表2。
表2胶束粒径及电位测定结果
由表2可知,实施例1至实施例3中抗菌胶束粒径分布均匀、分散性良好,对比实施例1中空白胶束及实施例1至实施例3中抗菌胶束均带正电荷。
实施例6
胶束物理稳定性测定
胶束在生理条件或PBS缓冲液中保持物理稳定性关系到胶束贮存条件的选择,还影响着药物传递系统的有效性,以胶束粒径、活性物质含量为指标考察胶束的物理稳定性。将对比实施例1中空白胶束和实施例1中抗菌胶束分散在浓度为0.01mol/L,pH=7.4的PBS缓冲液,在4℃冷藏避光贮存,7天内每天测定各胶束的粒径,并测量实施例1中抗菌胶束中活性物质含量的变化,考察胶束在避光、冷藏的贮存条件下的稳定性(n=3)。
7天内两种胶束粒径变化如图1所示,由图1可知,在4℃条件下,两种胶束粒径未发生明显变化,7d后空白胶束、实施例1中抗菌胶束在PBS缓冲液中的平均粒径分别是:12.3±1.7nm、83.2±2.1nm,PDI均小于0.3,两种胶束的粒径与冷藏前基本一致。
7天内实施例1中抗菌胶束中活性物质含量的变化如图2所示,由图2可知,7d内该抗菌胶束中活性物质含量均无显著性变化,表明本发明中抗菌胶束适宜在4℃冷藏避光贮存。
实施例7
体外释放性能测定
采用透析袋法测定实施例1至实施例3中抗菌胶束的体外释放性能,选取浓度为0.01mol/L,pH=7.4的PBS缓冲液作为释放介质,释放介质中均添加有0.1%吐温80溶液,以达到漏槽条件。取2mL实施例1至实施例3中抗菌胶束分别置于透析袋(Mw=3500Da)中,将透析袋放入装有50mL释放介质的棕色广口瓶中,置于温度为37℃,转速为100rpm的恒温振荡器中,设定的时间点0、0.25、0.5、1、2、3、6、10、12h取样,计算药物含量及累积释放度,绘制累积释放曲线。累计释放率的计算公式如下:
式中:Cn为第n次取样时释放介质的浓度,μg·mL-1;
V为释放介质的体积,mL;
Ci为第i次取样时释放介质的浓度,μg·mL-1;
Vi为释放介质的体积,mL;
w为胶束中药物的含量,mg。
实施例1至实施例3中抗菌胶束的累积释放曲线如图3所示,由图3可知,刚开始抗菌胶束释药速率最快,随后各抗菌胶束释药速率逐渐减缓,12h后各抗菌胶束释药速率逐渐达到平台期。实施例1至实施例3中抗菌胶束在12h后的累积释放百分数达到55%以上。
实施例8
抗菌性能测定
以革兰氏阳性菌金黄色葡萄球菌和革兰氏阴性菌大肠杆菌作为实验菌种。实验菌株在实验前用固体培养基连续传代培养3次,然后配制细菌悬浮液,将金黄色葡萄球茵和大肠杆菌分别在胰蛋白酶大豆液体培养基中培养18h后,将细菌悬浮液稀释至5×106CFU/mL。通过肉汤微量稀释法分别测试实施例1中抗菌胶束和对比实施例2中胶束的最低抑菌浓度,结果见表3。
表3抗菌性能测定结果
由表3可知,实施例1中抗菌胶束对两种菌的最低抑菌均浓度远远小于对比实施例2中胶束对两种菌的最低抑菌浓度,实施例1中抗菌胶束具有较好的抗菌性能。
最后说明的是,以上实施例仅用以说明本发明的技术方案而非限制,尽管参照较佳实施例对本发明进行了详细说明,本领域的普通技术人员应当理解,可以对本发明的技术方案进行修改或者等同替换,而不脱离本技术方案的宗旨和范围,其均应涵盖在本发明的权利要求范围当中。
Claims (10)
1.一种抗菌胶束,其特征在于,按重量百分比计,所述抗菌胶束包括如下组份:L-苯丙氨酸季铵盐8-15%,余量为水。
2.如权利要求1所述的一种抗菌胶束,其特征在于,按重量百分比计,所述抗菌胶束还包括活性成分0.1-3%。
3.如权利要求2所述的一种抗菌胶束,其特征在于,所述活性成分包括依沙吖啶、依托度酸、酮洛芬、普拉洛芬、氟比洛芬、美洛昔康、阿克他利、舒林酸、塞来昔布、噻洛芬酸、替诺昔康、萘普生、吡罗昔康、联苯乙酸、阿西美辛、安吡昔康、氨芬酸、布洛芬、扎托洛芬、双氯芬酸、吲哚美辛、莫苯唑酸、洛索洛芬、氯苯扎利或氯诺昔康中的至少一种。
4.如权利要求1-3任一项所述的一种抗菌胶束,其特征在于,按重量百分比计,所述抗菌胶束还包括皮肤外用制剂中可接受的辅料4-22%。
5.如权利要求4所述的一种抗菌胶束,其特征在于,所述辅料包括保湿剂、增稠剂和防腐剂;所述保湿剂占所述抗菌胶束总重量的3-10%,所述增稠剂占所述抗菌胶束总重量的0.1-2%,所述防腐剂占所述抗菌胶束总重量的1-10%。
6.如权利要求5所述的一种抗菌胶束,其特征在于,所述保湿剂为1,3-丁二醇、1,3-丙二醇、乳酸钠、甘油、羟乙基脲、透明质酸钠、甲壳素、甲壳素衍生物或植物多糖提取物中的至少一种;所述增稠剂为聚丙烯酸酯交联聚合物-6、丙烯酸羟乙酯/丙烯酰二甲基牛磺酸钠共聚物、聚丙烯酸钠、聚丙烯酸类聚合物、黄原胶或羟乙基纤维素中的至少一种;所述防腐剂为苯氧基乙醇、对羟基苯甲酸甲酯、对羟基苯甲酸丙酯或山梨醇中的至少一种。
7.如权利要求1所述的一种抗菌胶束,其特征在于,所述L-苯丙氨酸季铵盐按如下方法制备:
(1)在-4-0℃下,将L-苯丙氨酸溶于辛醇、十四醇或十六醇中,然后滴入二氯亚砜,于25-28℃下以200-500rpm的速度搅拌反应2-3d后固液分离,将获得的固相物质I用乙醚洗涤,制得L-苯丙氨酸酯盐,所述L-苯丙氨酸溶于辛醇、二氯亚砜与辛醇、十四醇或十六醇的质量体积比为0.5-2:1-2:10-15,g:mL:mL;
(2)将步骤(1)中制得的L-苯丙氨酸酯盐和碳酸钾溶解于乙腈中,再加入溴乙烷,混匀后升温至90-95℃后以200-500rpm的速度搅拌反应12-24h,然后去除过量的碳酸钾和乙腈后固液分离,将获得的固相物质II用乙醚洗涤,制得L-苯丙氨酸季铵盐,所述L-苯丙氨酸酯盐、碳酸钾、乙腈与溴乙烷的质量体积比为1-3:1-1.5:10-20:4-6。
8.权利要求1-7任一项所述的一种抗菌胶束的制备方法,其特征在于,所述方法如下:
A、将皮肤外用制剂中可接受的辅料溶于PBS缓冲液中,获得溶液I;
B、将L-苯丙氨酸季铵盐和活性成分加入二氯甲烷和甲醇的混合液中,混匀后旋转蒸发至所述混合液挥发,形成一层透明薄膜,再加入步骤A中的溶液I,超声至所述透明薄膜溶解,以100-300rpm的速度搅拌6-12h,过滤后得固相物质III,将所述固相物质III冷冻干燥后溶于水,即可。
9.如权利要求8所述的方法,其特征在于,步骤B中,所述混匀后旋转蒸发具体为:混匀后于40-50℃下以100-200rpm的速度旋转蒸发。
10.如权利要求8所述的方法,其特征在于,步骤B中,所述冷冻干燥后溶于水具体为:对冷冻干燥后的产物中各组分含量进行测试,然后根据对抗菌胶束中各组分含量的实际需求设定所述产物和水的用量,将所述产物溶于水,即可。
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