CN113876959A - 一种生物载体、制备方法及应用 - Google Patents
一种生物载体、制备方法及应用 Download PDFInfo
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- CN113876959A CN113876959A CN202111197533.XA CN202111197533A CN113876959A CN 113876959 A CN113876959 A CN 113876959A CN 202111197533 A CN202111197533 A CN 202111197533A CN 113876959 A CN113876959 A CN 113876959A
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Images
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Abstract
一种生物载体、制备方法及应用,属于功能材料技术领域,生物载体由醇溶性负载物、醇溶性植物蛋白、第二组分组成;其中,醇溶性植物蛋白占1重量份,醇溶性物质占0.001~1重量份,第二组分占0.1~3重量份。通过疏水作用等多重作用将醇溶性物质在乙醇中与醇溶性植物蛋白相结合及反溶剂法,制备负载醇溶性物质的生物载体,其粒径为100‑1000nm。制得的生物载体具有pH稳定性,适用的pH范围广,可以制备生物载体用于负载药物、香精等活性成分,适用于对光敏感或易老化的物质的运载缓释,可以用于口服药物及静脉注射。
Description
技术领域
本发明涉及一种生物载体的制备方法,具体涉及一种生物载体的制备方法及其应用,属于功能材料技术领域。
背景技术
在过去的几十年里,随着人们饮食习惯的改变,伴随而来的是大大小小的疾病,在医学领域,很多生物活性物质和药物,难溶于水,且需要其在人体中持续较长的时间,因此,需要具有一定缓释能力的运载体系。
常见的运载体系有:乳液,脂质体,微胶囊,纳米颗粒等。常见的纳米载体有许多,但大都具有较差的生物相容性和缓释性能,常常通过静脉注射的方法进行使用而无法口服,即无法在偏酸性的环境中使用;且一些生物活性物质对环境相对敏感,因此需要纳米载体具有一定的抗光氧老化性,因此生物载体进入了人们的视野。如赵雪等利用多孔淀粉微球包覆青蒿素,不仅缺乏抗光氧老化性且其在酸性条件下仅能释放原药的1.64倍,酸性条件下效果不甚理想(Chinese Traditional and Herbal Drugs.2019,50,7:1596-1602)。
纳米包封技术作为纳米技术的一个重要分支,能将生物活性成分包埋于纳米颗粒内部或吸附于纳米颗粒表面,使其免受环境不利因素的影响,从而达到延缓释放、提高生物利用度的目的。近年来,以脂类、多糖和蛋白质为材料制备的生物载体具有良好的生物相容性、生物降解性和无毒性,因此,收到了广泛的关注。
发明内容
针对以上问题,本发明提供了一种生物载体,其特征在于,所述生物载体由醇溶性物质、醇溶性植物蛋白、第二组分组成;其中,醇溶性植物蛋白占1重量份,醇溶性物质占0.001~1重量份,第二组分占0.1~3重量份;所述生物载体的粒径为100-1000nm。
一种生物载体,其特征在于,醇溶性物质为可溶于醇水溶液的醇溶性香精如香叶精,香草醇,橙花醇,椰子醛等,或醇溶性药物如姜黄素,青蒿素类药物,喹诺酮类,维生素,阿司匹林,布洛芬,金丝桃苷,尿苷等;所述醇溶性植物蛋白优选为玉米醇溶蛋白、小麦醇溶蛋白的一种或组合;所述第二组分为多糖类、改性多糖、含邻苯二酚的物质、多环氧官能团的物质、多醛基物质、多胺基物质或多羧基物质及离子盐。
一种生物载体,其特征在于,醇溶性物质优选为青蒿素,双氢青蒿素,脱氧青蒿素,蒿甲醚,蒿乙醚,尿苷等。
一种生物载体,其特征在于,第二组分为多糖纤维素、改性纤维素、淀粉、改性淀粉、壳聚糖、改性壳聚糖、海藻酸钠、甲壳素、改性甲壳素、阿拉伯胶、改性阿拉伯胶、果胶、改性果胶、糖原、改性糖原、多聚果糖、改性多聚果糖、单宁酸、改性单宁酸、儿茶酚、盐酸多巴胺、聚多巴胺、低聚多巴胺、乙二醇二缩水甘油醚、邻苯二醛、乙二胺、咖啡酸、柠檬酸,CaCl2中的一种或两种以上组合。
一种生物载体,其特征在于,所述的第二组分优选为果胶、壳聚糖、海藻酸钠、TEMPO氧化纤维素、NaIO4氧化纤维素、TEMPO改性双醛纤维素、NaIO4氧化海藻酸钠、TEMPO氧化淀粉、NaIO4氧化淀粉、TEMPO改性双醛淀粉、NaIO4氧化聚甘油中的一种或两种以上组合。
一种生物载体的制备方法,其特征在于,所述制备方法与原理为通过疏水作用等多重作用将醇溶性物质在乙醇中与醇溶性植物蛋白相结合,后通过反溶剂法,将上述醇水溶液倒入第二组分的溶液中,制备负载醇溶性物质的生物载体。
一种生物载体的制备方法,其特征在于,所述制备方法包括以下步骤:
(1)将醇溶性植物蛋白和醇溶性物质溶于醇水溶液中;
(2)将第二组分溶于溶液中,或者将第二组分分散于分散液中;
(3)将步骤(1)的醇水溶液缓慢倒入步骤(2)的溶液中,调节pH=3-14,在30-90℃下搅拌0.25-24h,得到玉米醇溶蛋白与第二组分制备的生物载体粒子的分散液,调节pH=7;
(4)将制备得到的生物载体生物载体粒子分散液,首先通过旋蒸去除其中的乙醇,通过调节pH=1-3、离心或透析进行分离提纯,后经过冷冻干燥得到负载醇溶性物质的生物载体。
一种生物载体的制备方法,其特征在于,步骤(1)中醇水溶液中乙醇占体积比为80-92%;步骤(4)中,旋蒸温度为30-60℃,时间为2-15min,冷冻干燥温度为-10~-50℃,冷冻干燥时间为12h~72h,离心分离时离心转速为4000~15000r/min,离心时间为3~15min。
一种生物载体的应用,其特征在于,所述生物载体具有pH稳定性,适用的pH范围为1.5-10。
所述的生物载体,其特征在于,所述负载醇溶性物质的生物载体具有抗光老化和抗氧化性,适用于对光敏感或易老化的物质的运载缓释,可以用于口服药物及静脉注射。
本发明的有益效果:
本发明制备的生物载体是由醇溶性物质、醇溶性植物蛋白和第二组分通过静电作用键作用或者多重作用制备而来的,其生物相容性,稳定性,分散性较为优异。
本发明制备的生物载体在酸性、中性弱碱性条件下,均可稳定存在,且所述负载醇溶性物质的生物载体具有较好的缓释性能,可极大提高药物在身体的存在时间,且所述负载醇溶性物质的生物载体有一定的抗光老化和氧化的能力可以对光敏感,易老化的物质起到一定的保护作用。
综上所述,本发明制备的生物载体有望实现在香精、医用以及护肤等领域的广泛应用。
附图说明
图1为实例1制备的的生物载体1在pH=2,5,7,9的粒径分布图,由图可得,生物载体1在pH=2-9这一较广的酸碱范围内仍具有较好的分散性,有利于解决口服药物在人体不同位置,不同pH环境下的分散性问题。
图2为实施例1制备的生物载体1在模仿胃酸(pH=2)和体液(pH=7)的缓释曲线,由图可得,生物载体在模仿胃酸(pH=2)和体液(pH=7)的环境下仍具备较好的缓释性能,且在胃酸中释放效率较高,有利于使药物维持在理想浓度范围内。
具体实施方法
下面结合实施例,进一步说明本发明。
TEMPO氧化纤维素是参考[TEMPO氧化纤维素纳米纤维的制备及应用研究进展.材料工程,2015(43):84-91.]公开方法制备TEMPO氧化纤维素。具体制备方法如下:将1g纤维素置于100ml去离子水中,加入0.016gTEMPO,0.1gNaBr和6ml的NaClO,在45℃条件下,调节pH=10-10.5,磁力搅拌反应6h,加入2ml乙二醇终止反应,后离心,水洗,冷冻干燥得TEMPO氧化纤维素。
NaIO4氧化纤维素参考[微晶纤维素表面接枝对苯二胺的制备及其荧光性能.材料导报,2016(A1):241-243.]公开方法,自制NaIO4氧化纤维素。具体制备方法如下:将1g纤维素放于100ml pH 4.6的醋酸-醋酸钠缓冲液中,加入1.5gNaIO4,避光反应4h,加入2ml乙二醇终止反应,后离心,水洗,冷冻干燥得NaIO4氧化纤维素。
TEMPO改性双醛纤维素即先通过上述方法TEMPO氧化后在进行NaIO4氧化,自制TEMPO改性双醛纤维素。具体制备方法如下:将1g纤维素置于100ml去离子水中,加入0.016gTEMPO,0.1gNaBr和6ml的NaClO,在45℃条件下,调节pH 10-10.5,磁力搅拌反应6h,加入2ml乙二醇终止反应,后离心,水洗,冷冻干燥得TEMPO氧化纤维素。后将1gTEMPO氧化纤维素分散于于100ml pH=4.6的醋酸-醋酸钠缓冲液中,加入1.5gNaIO4,避光反应4h,加入2ml乙二醇终止反应,后离心,水洗,冷冻干燥得TEMPO改性双醛纤维素。
NaIO4氧化海藻酸钠是参考[部分氧化海藻酸钠的制备与性能.应用化学.2005,(09):1007-1011.]公开方法,自制NaIO4氧化海藻酸钠。具体制备方法如下:将1g海藻酸钠放于100ml去离子水中中,加入1.5gNaIO4,避光反应4h,加入2ml乙二醇终止反应,后离心,水洗,冷冻干燥得NaIO4氧化海藻酸钠。
TEMPO氧化淀粉是参考[Characterization of starch films impregnated withstarch nanoparticles prepared by2,2,6,6-tetramethylpiperidine-1-oxyl(TEMPO)-mediated oxidation.Food Chemistry.2016,192,865-872.]公开方法,自制TEMPO氧化淀粉。具体制备方法如下:将1g淀粉置于100ml去离子水中,加入0.016gTEMPO,0.1gNaBr和6ml的NaClO,在45℃条件下,调节pH=10-10.5,磁力搅拌反应6h,加入2ml乙二醇终止反应,后离心,水洗,冷冻干燥得TEMPO氧化淀粉。
NaIO4氧化淀粉是参考[Preparation and characterization of dialdehydestarch by one-step acid hydrolysis and oxidation.InternationalJournalofBiologicalmacromolecules.2017,103,1257-1264.]公开方法,自制NaIO4氧化淀粉。具体制备方法如下:将1g淀粉放于100ml去离子水中,加入1.5gNaIO4,避光反应4h,加入2ml乙二醇终止反应,后离心,水洗,冷冻干燥得NaIO4氧化淀粉。
TEMPO改性双醛淀粉即先通过上述方法TEMPO改性后在进行NaIO4改性,自制TEMPO改性双醛淀粉。具体制备方法如下:1g淀粉置于100ml去离子水中,加入0.016gTEMPO,0.1gNaBr和6ml的NaClO,在45℃条件下,调节pH=10-10.5,磁力搅拌反应6h,加入2ml乙二醇终止反应,后离心,水洗,冷冻干燥得TEMPO氧化淀粉。。将1gTEMPO氧化淀粉放于100ml pH=4.6的醋酸-醋酸钠缓冲液中,加入1.5gNaIO4,避光反应4h,加入2ml乙二醇终止反应,后离心,水洗,冷冻干燥得TEMPO改性双醛淀粉。
NaIO4氧化聚甘油即将低分子量的聚甘油溶于水中加入不同含量的高碘酸钠制备、NaIO4氧化聚甘油。具体制备方法如下:将1g十聚甘油放于100ml去离子水中中,加入1.5gNaIO4,避光反应4h,加入2ml乙二醇终止反应,后透析得NaIO4氧化聚甘油的分散液。
一、杂化生物粒子的合成
实施例1
(1)将0.5g玉米醇溶蛋白和0.3g青蒿素溶于50ml的醇水溶液(乙醇占90v/v%)中,得到溶液A
(2)将1g果胶溶于100ml水中,得到溶液B。
(3)取6ml溶液B,置于14ml去离子水中,调节pH=7,在搅拌的同时,逐滴加入10ml溶液A,在室温下搅拌15min,得到玉米醇溶蛋白、青蒿素与第二组分制备的复合生物载体粒子的分散液,调节pH=7。
(4)将制备得到的玉米蛋白复合生物载体粒子分散液首先通过45℃旋蒸5min去除其中得乙醇,得到玉米醇溶蛋白复合生物载体粒子生物载体粒子,将制备得到的生物载体分散液通过两次离心,离心速度10000r/min,离心时间10min,后经过-20℃冷冻干燥48h得到生物载体1。
实施例2
(1)将0.5g玉米醇溶蛋白和0.3g青蒿素溶于50ml的醇水溶液(乙醇占90v/v%)中,得到溶液A
(2)将1g果胶溶于100ml水中,得到溶液B
(3)取10ml溶液B,置于10ml去离子水中,调节pH=7,在搅拌的同时,逐滴加入10ml溶液A调节pH=7,在室温下搅拌15min,得到玉米醇溶蛋白、青蒿素与第二组分制备的复合生物载体粒子生物载体粒子的分散液,调节pH=7。
(4)将制备得到的玉米蛋白复合生物载体粒子生物载体粒子分散液首先通过45℃旋蒸5min去除其中得乙醇,得到玉米醇溶蛋白复合生物载体粒子生物载体粒子,将制备得到的生物载体分散液通过两次离心,离心速度10000r/min,离心时间10min,后经过-20℃冷冻干燥48h得到生物载体2。
实施例3
(1)将0.5g玉米醇溶蛋白和0.1g青蒿素溶于50ml的醇水溶液(乙醇占90v/v%)中,得到溶液A
(2)将1g果胶溶于100ml水中,得到溶液B
(3)取6ml溶液B,置于14ml去离子水中,调节pH=7,在搅拌的同时,逐滴加入10ml溶液A调节pH=7,在室温下搅拌15min,得到玉米醇溶蛋白、青蒿素与第二组分制备的复合生物载体粒子生物载体粒子的分散液,调节pH=7。
(4)将制备得到的玉米蛋白复合生物载体粒子生物载体粒子分散液首先通过45℃旋蒸5min去除其中得乙醇,得到玉米醇溶蛋白复合生物载体粒子生物载体粒子,将制备得到的生物载体分散液通过两次离心,离心速度10000r/min,离心时间10min,后经过-20℃冷冻干燥48h得到生物载体3。
实施例4
(1)将0.5g玉米醇溶蛋白和0.1g青蒿素溶于50ml的醇水溶液(乙醇占90v/v%)中,得到溶液A
(2)将1g果胶溶于100ml水中,得到溶液B
(3)取10ml溶液B,置于10ml去离子水中,调节pH=7,在搅拌的同时,逐滴加入10ml溶液A调节pH=7,在室温下搅拌15min,得到玉米醇溶蛋白、青蒿素与第二组分制备的复合生物载体粒子生物载体粒子的分散液,调节pH=7。
(4)将制备得到的玉米蛋白复合生物载体粒子生物载体粒子分散液首先通过45℃旋蒸5min去除其中得乙醇,得到玉米醇溶蛋白复合生物载体粒子生物载体粒子,将制备得到的生物载体分散液通过两次离心,离心速度10000r/min,离心时间10min,后经过-20℃冷冻干燥48h得到生物载体4。
实施例5
(1)将0.5g玉米醇溶蛋白和0.1g青蒿素溶于50ml的醇水溶液(乙醇占90v/v%)中,得到溶液A
(2)将1g壳聚糖溶于100ml醋酸水溶液(3wt%)中,得到溶液B
(3)取10ml溶液B,置于10ml去离子水中,调节pH=3,在搅拌的同时,逐滴加入10ml溶液A调节pH=7,在室温下搅拌15min,得到玉米醇溶蛋白、青蒿素与第二组分制备的复合生物载体粒子生物载体粒子的分散液,调节pH=7。
(4)将制备得到的玉米蛋白复合生物载体粒子分散液首先通过45℃旋蒸5min去除其中得乙醇,得到玉米醇溶蛋白复合生物载体粒子,将制备得到的生物载体分散液通过两次离心,离心速度10000r/min,离心时间10min,后经过-20℃冷冻干燥48h得到生物载体5。
实施例6
(1)将0.5g玉米醇溶蛋白和0.1g青蒿素溶于50ml的醇水溶液(乙醇占90v/v%)中,得到溶液A
(2)将1g壳聚糖溶于100ml醋酸水溶液(3wt%)中,得到溶液B.
(3)将1g海藻酸钠溶于100ml水中,得到溶液C.
(4)取10ml溶液B,置于10ml去离子水中,调节pH=3,在搅拌的同时,逐滴加入10ml溶液A调节pH=7,在室温下搅拌15min,后加入10ml溶液C,在室温下搅拌15min,得到玉米醇溶蛋白、青蒿素与第二组分制备的复合生物载体粒子的分散液,调节pH=7。
(4)将制备得到的玉米蛋白复合生物载体粒子分散液首先通过45℃旋蒸5min去除其中得乙醇,得到玉米醇溶蛋白复合生物载体粒子,将制备得到的生物载体分散液通过两次离心,离心速度10000r/min,离心时间10min,后经过-20℃冷冻干燥48h得到生物载体6。
实施例7
(1)将0.5g玉米醇溶蛋白和0.1g青蒿素溶于50ml的醇水溶液(乙醇占90v/v%)中,得到溶液A
(2)将1g壳聚糖溶于100ml醋酸水溶液(3wt%)中,得到溶液B.
(3)将1g海藻酸钠溶于100ml水中,得到溶液C.
(4)将0.1gCaCl2溶于100ml水,得到溶液D
(4)取10ml溶液B,置于10ml去离子水中,调节pH=3,在搅拌的同时,逐滴加入10ml溶液A调节pH=7,在室温下搅拌15min,后加入10ml溶液C,在室温下搅拌15min,后加入10ml溶液D,得到玉米醇溶蛋白、青蒿素与第二组分制备的复合生物载体粒子的分散液,调节pH=7。
(4)将制备得到的玉米蛋白复合生物载体粒子分散液首先通过45℃旋蒸5min去除其中得乙醇,得到玉米醇溶蛋白复合生物载体粒子,将制备得到的生物载体分散液通过两次离心,离心速度10000r/min,离心时间10min,后经过-20℃冷冻干燥48h得到生物载体7。
实施例8
(1)将0.5g玉米醇溶蛋白和0.3g青蒿素溶于50ml的醇水溶液(乙醇占90v/v%)中,得到溶液A
(2)将1gTEMPO氧化纤维素溶于100ml水中,得到溶液B
(3)取6ml溶液B,置于14ml去离子水中,调节pH=7,在搅拌的同时,逐滴加入10ml溶液A调节pH=7,在室温下搅拌15min,得到玉米醇溶蛋白、青蒿素与第二组分制备的复合生物载体粒子的分散液,调节pH=7。
(4)将制备得到的玉米蛋白复合生物载体粒子分散液首先通过45℃旋蒸5min去除其中得乙醇,得到玉米醇溶蛋白复合生物载体粒子,将制备得到的生物载体分散液通过两次离心,离心速度10000r/min,离心时间10min,后经过-20℃冷冻干燥48h得到生物载体8。
实施例9
(1)将0.5g玉米醇溶蛋白和0.3g青蒿素溶于50ml的醇水溶液(乙醇占90v/v%)中,得到溶液A
(2)将1gNaIO4氧化纤维素溶于100ml水中,得到溶液B
(3)取6ml溶液B,置于14ml去离子水中,调节pH=7,在搅拌的同时,逐滴加入10ml溶液A调节pH7,在室温下搅拌15min,得到玉米醇溶蛋白、青蒿素与第二组分制备的复合生物载体粒子的分散液,调节pH=7。
(4)将制备得到的玉米蛋白复合生物载体粒子分散液首先通过45℃旋蒸5min去除其中得乙醇,得到玉米醇溶蛋白复合生物载体粒子,将制备得到的生物载体分散液通过两次离心,离心速度10000r/min,离心时间10min,后经过-20℃冷冻干燥48h得到生物载体9。
实施例10
(1)将0.5g玉米醇溶蛋白和0.3g青蒿素溶于50ml的醇水溶液(乙醇占90v/v%)中,得到溶液A
(2)将1gTEMPO改性双醛纤维素溶于100ml水中,得到溶液B
(3)取6ml溶液B,置于14ml去离子水中,调节pH=7,在搅拌的同时,逐滴加入10ml溶液A调节pH=7,在室温下搅拌15min,得到玉米醇溶蛋白、青蒿素与第二组分制备的复合生物载体粒子的分散液,调节pH=7。
(4)将制备得到的玉米蛋白复合生物载体粒子分散液首先通过45℃旋蒸5min去除其中得乙醇,得到玉米醇溶蛋白复合生物载体粒子,将制备得到的生物载体分散液通过两次离心,离心速度10000r/min,离心时间10min,后经过-20℃冷冻干燥48h得到生物载体10。
实施例11
(1)将0.5g玉米醇溶蛋白和0.3g青蒿素溶于50ml的醇水溶液(乙醇占90v/v%)中,得到溶液A
(2)将1gNaIO4氧化海藻酸钠溶于100ml水中,得到溶液B
(3)取6ml溶液B,置于14ml去离子水中,调节pH=7,在搅拌的同时,逐滴加入10ml溶液A调节pH=7,在室温下搅拌15min,得到玉米醇溶蛋白、青蒿素与第二组分制备的复合生物载体粒子的分散液,调节pH7。
(4)将制备得到的玉米蛋白复合生物载体粒子分散液首先通过45℃旋蒸5min去除其中得乙醇,得到玉米醇溶蛋白复合生物载体粒子,将制备得到的生物载体分散液通过两次离心,离心速度10000r/min,离心时间10min,后经过-20℃冷冻干燥48h得到生物载体11。
实施例12
(1)将0.5g玉米醇溶蛋白和0.3g青蒿素溶于50ml的醇水溶液(乙醇占90v/v%)中,得到溶液A
(2)将1gTEMPO氧化淀粉溶于100ml水中,得到溶液B
(3)取6ml溶液B,置于14ml去离子水中,调节pH=7,在搅拌的同时,逐滴加入10ml溶液A调节pH=7,在室温下搅拌15min,得到玉米醇溶蛋白、青蒿素与第二组分制备的复合生物载体粒子的分散液,调节pH=7。
(4)将制备得到的玉米蛋白复合生物载体粒子分散液首先通过45℃旋蒸5min去除其中得乙醇,得到玉米醇溶蛋白复合生物载体粒子,将制备得到的生物载体分散液通过两次离心,离心速度10000r/min,离心时间10min,后经过-20℃冷冻干燥48h得到生物载体12。
实施例13
(1)将0.5g玉米醇溶蛋白和0.3g青蒿素溶于50ml的醇水溶液(乙醇占90v/v%)中,得到溶液A
(2)将1gNaIO4氧化淀粉溶于100ml水中,得到溶液B
(3)取6ml溶液B,置于14ml去离子水中,调节pH=7,在搅拌的同时,逐滴加入10ml溶液A调节pH=7,在室温下搅拌15min,得到玉米醇溶蛋白、青蒿素与第二组分制备的复合生物载体粒子的分散液,调节pH=7。
(4)将制备得到的玉米蛋白复合生物载体粒子分散液首先通过45℃旋蒸5min去除其中得乙醇,得到玉米醇溶蛋白复合生物载体粒子,将制备得到的生物载体分散液通过两次离心,离心速度10000r/min,离心时间10min,后经过-20℃冷冻干燥48h得到生物载体13。
实施例14
(1)将0.5g玉米醇溶蛋白和0.3g青蒿素溶于50ml的醇水溶液(乙醇占90v/v%)中,得到溶液A
(2)将1gTEMPO改性双醛淀粉溶于100ml水中,得到溶液B
(3)取6ml溶液B,置于14ml去离子水中,调节pH=7,在搅拌的同时,逐滴加入10ml溶液A调节pH=7,在室温下搅拌15min,得到玉米醇溶蛋白、青蒿素与第二组分制备的复合生物载体粒子的分散液,调节pH=7。
(4)将制备得到的玉米蛋白复合生物载体粒子分散液首先通过45℃旋蒸5min去除其中得乙醇,得到玉米醇溶蛋白复合生物载体粒子,将制备得到的生物载体分散液通过两次离心,离心速度10000r/min,离心时间10min,后经过-20℃冷冻干燥48h得到生物载体15。
实施例15
(1)将0.5g玉米醇溶蛋白和0.3g青蒿素溶于50ml的醇水溶液(乙醇占90v/v%)中,得到溶液A
(2)将1gNaIO4氧化聚甘油溶于100ml水中,得到溶液B
(3)取6ml溶液B,置于14ml去离子水中,调节pH=7,在搅拌的同时,逐滴加入10ml溶液A调节pH=7,在室温下搅拌15min,得到玉米醇溶蛋白、青蒿素与第二组分制备的复合生物载体粒子的分散液,调节pH=7。
(4)将制备得到的玉米蛋白复合生物载体粒子分散液首先通过45℃旋蒸5min去除其中得乙醇,得到玉米醇溶蛋白复合生物载体粒子,将制备得到的生物载体分散液通过两次离心,离心速度10000r/min,离心时间10min,后经过-20℃冷冻干燥48h得到生物载体15。
实施例16
(1)将0.5g玉米醇溶蛋白和0.3g尿苷溶于50ml的醇水溶液(乙醇占90v/v%)中,得到溶液A
(2)将1g果胶溶于100ml水中,得到溶液B
(3)取6ml溶液B,置于14ml去离子水中,调节pH=7,在搅拌的同时,逐滴加入10ml溶液A调节pH=7,在室温下搅拌15min,得到玉米醇溶蛋白、青蒿素与第二组分制备的复合生物载体粒子的分散液,调节pH=7。
(4)将制备得到的玉米蛋白复合生物载体粒子分散液首先通过45℃旋蒸5min去除其中得乙醇,得到玉米醇溶蛋白复合生物载体粒子,将制备得到的生物载体15分散液通过两次离心,离心速度10000r/min,离心时间10min,后经过-20℃冷冻干燥48h得到生物载体16。
对比例1
将0.3mg青蒿素溶于50ml醇水溶液中,倒入20ml去离子水中,直接调节pH=7,后旋蒸,离心,离心速度10000r/min,离心时间10min,后经过-20℃冷冻干燥48h得针状青蒿素。
对比例2
将实施例1(1)中的分散液A,倒入20ml去离子水中,直接调节pH=7,后旋蒸,离心,离心速度10000r/min,离心时间10min,后经过-20℃冷冻干燥48h得生物载体对比样。
载药率:将10mg制备的生物载体溶于醇水溶液(乙醇占90v/v%)中,利用HPLC测定其中负载物的量,利用以下公式测定负载物的载药率:
缓释性能测试:将10mg生物载体溶于于pH=7的PBS缓冲液中,在0.5h,1h,4h,12h,24h,36h取样,利用HPLC测定其中负载物的量,从而测试其缓释效果。利用缓释半衰期(药物释放50%的时间)来评判缓释效果。
pH稳定性测试:测试生物载体在弱酸性及中性条件下的分散情况,观察其是否产生聚集现象。
与对比例1相比,对比例1和实施例制备的生物载体有效解决了醇溶性物质的溶解性问题。
与对比例2相比,实施例制备的生物载体有更好的缓释性能,且具有更佳的pH稳定性,可以在弱酸性、中性、弱碱性的条件下分散。
本发明的生物载体粒径在100-1000nm之间,具有更高的pH稳定性,缓释性能和载药率,可以应用于包覆香料、活性物质,制备静脉注射药物、口服药物等。
结合图1和图2由图可以看出,制备的生物载体不论在酸性条件下、中性条件下及碱性条件下有较好的缓释性能,且不论在较广的酸碱性下都具有较好的分散性,因此有利于应用于口服药物。
Claims (10)
1.一种生物载体,其特征在于,所述生物载体由醇溶性负载物、醇溶性植物蛋白、第二组分组成;其中,醇溶性植物蛋白占1重量份,醇溶性负载物占0.001~1重量份,第二组分占0.1~3重量份;所述生物载体的粒径为100-1000nm;所述第二组分为多糖、改性多糖、含邻苯二酚的物质、多环氧官能团的物质、多醛基物质、多胺基物质或多羧基物质或离子盐。
2.根据权利要求1所述的一种生物载体,其特征在于,醇溶性负载物为可溶于醇水溶液的醇溶性香精或醇溶性药物;所述醇溶性植物蛋白优选为玉米醇溶蛋白、小麦醇溶蛋白的一种或组合。
3.根据权利要求2所述的一种生物载体,其特征在于,所述的醇溶性香精为香叶精、香草醇、橙花醇或椰子醛,所述的醇溶性药物为姜黄素、青蒿素类药物、喹诺酮类、维生素、阿司匹林、布洛芬、金丝桃苷或尿苷;优选为青蒿素、双氢青蒿素、脱氧青蒿素、蒿甲醚、蒿乙醚、尿苷。
4.根据权利要求1、2或3所述的一种生物载体,其特征在于,第二组分为多糖纤维素、改性纤维素、淀粉、改性淀粉、壳聚糖、改性壳聚糖、海藻酸钠、甲壳素、改性甲壳素、阿拉伯胶、改性阿拉伯胶、果胶、改性果胶、糖原、改性糖原、多聚果糖、改性多聚果糖、单宁酸、改性单宁酸、儿茶酚、盐酸多巴胺、聚多巴胺、低聚多巴胺、乙二醇二缩水甘油醚、邻苯二醛、乙二胺、咖啡酸、柠檬酸,CaCl2中的一种或两种以上组合。
5.根据权利要求4所述的一种生物载体,其特征在于,所述的第二组分果胶、壳聚糖、海藻酸钠、TEMPO氧化纤维素、NaIO4氧化纤维素、TEMPO改性双醛纤维素、NaIO4氧化海藻酸钠、TEMPO氧化淀粉、NaIO4氧化淀粉、TEMPO改性双醛淀粉、NaIO4氧化聚甘油中的一种或两种以上组合。
6.权利要求1-5任一所述的一种生物载体的制备方法,其特征在于,所述制备方法与原理为醇溶性负载物在乙醇中与醇溶性植物蛋白相结合,后通过反溶剂法,将上述醇水溶液倒入第二组分的溶液中,制备负载醇溶性物质的生物载体。
7.根据权利要求6所述的一种生物载体的制备方法,其特征在于,所述制备方法包括以下步骤:
(1)将醇溶性植物蛋白和醇溶性负载物溶于醇水溶液中;
(2)将第二组分溶于溶液中,或者将第二组分分散于分散液中;
(3)将步骤(1)的醇水溶液缓慢倒入步骤(2)的溶液中,调节pH=3-14,在0-90℃下搅拌0.25-24h,得到玉米醇溶蛋白与第二组分制备的生物载体粒子的分散液,调节pH=7;
(4)将制备得到的玉米醇溶蛋白与第二组分制备的生物载体粒子的分散液,首先通过旋蒸去除其中的乙醇,通过调节pH=1-3、离心或透析进行分离提纯,后经过冷冻干燥得到负载醇溶性物质的生物载体。
8.根据权利要求7所述的一种生物载体的制备方法,其特征在于,步骤(1)中醇水溶液中乙醇占体积比为80-92%;步骤(4)中,旋蒸温度为30-60℃,时间为2-15min,冷冻干燥温度为-10~-50℃,冷冻干燥时间为12h~72h,离心分离时离心转速为4000~15000r/min,离心时间为3~15min。
9.权利要求1-5任一所述的一种生物载体的应用,其特征在于,所述生物载体用于口服药物及静脉注射,醇溶性负载物具有抗光老化和抗氧化性,进而用于对光敏感或易老化的物质的运载缓释。
10.如权利要求1-9任一所述的生物载体,其特征在于,所述的生物载体具有pH稳定性,适用的pH范围为1.5-10。
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