CN111264860A - 含有虾青素和槲皮素的固体自微乳微囊及其制备方法和应用 - Google Patents
含有虾青素和槲皮素的固体自微乳微囊及其制备方法和应用 Download PDFInfo
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- CN111264860A CN111264860A CN202010061251.6A CN202010061251A CN111264860A CN 111264860 A CN111264860 A CN 111264860A CN 202010061251 A CN202010061251 A CN 202010061251A CN 111264860 A CN111264860 A CN 111264860A
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- microemulsion
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- quercetin
- astaxanthin
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Abstract
本发明提供了一种含有虾青素和槲皮素的固体自微乳微囊及其制备方法和应用,该自微乳微囊包括虾青素、槲皮素、油相、乳化剂、助乳化剂和固体吸附剂;本发明从载药递送体系设计角度出发,将虾青素与槲皮素两者结合制备固体自微乳微囊体系,从而突破虾青素的传统单运载体系,槲皮素具有很高的安全性,能够抑制P‑gp对药物的外排作用,从而抑制药物代谢酶CYP3A4和药物转运蛋白P‑糖蛋白的活性,提高生物利用度,同时提高了虾青素的溶解性,从而使得槲皮素与虾青素复配可以发挥作用,不仅可以提高稳定性又能不影响虾青素的抗氧化能力;同时具有液态自微乳和固体制剂的优势,使药物的溶出度和生物利用度均得到提高。
Description
技术领域
本发明属于功能食品中的载体系统技术领域,具体涉及一种含有虾青素和槲皮素的固体自微乳微囊及其制备方法和应用。
背景技术
虾青素(Astaxanthin)是目前最强的抗氧化剂,近年来的研究表明,虾青素具有防治心血管疾病、降低血压、防治动脉粥样硬化、保护神经系统、缓解炎症、防治癌症、治疗肝损伤、减轻肥胖、防治糖尿病、保护皮肤、保护视力、减少运动损伤和增强免疫力等多方面的药理活性。虾青素也是目前发现唯一能穿透血-脑、血-视网膜屏障的类胡萝卜素,对中枢神经系统和大脑功能可产生积极的影响。因此若将虾青素作为膳食功能因子添加到食品当中,对改善人体健康将具有切实的意义。
由于虾青素具备广泛的药用价值和药理作用,其广阔的市场前景受到了人们的关注。但虾青素对光、热和氧敏感,在水中溶解度极低,口服吸收差、生物利用度低和首过效应强是虾青素的主要缺点,所以极大限制了它的临床应用。
目前市场上普遍运用的虾青素运载体系多数为单一递送体系,面临剂型单一少,应用范围窄的瓶颈。如脂质体体系仍存在一些亟须解决的问题:粒径分布范围广、负载率低、易氧化和稳定性差;随着储存时间的增加,脂质体存在易凝集和脂质层中不饱和脂肪酸易氧化。此外,较为常见的纳米乳液体系较传统乳液虽可以更好地提高生物活性物质的稳定性和生物利用度,但制备时高压均质和超声等操作易使体系中敏感化合物结构发生变化,生物活性降低等。因为药物进入体内通常发生外排作用,其生物学实质为:细胞对生存环境中所遇药物加以排斥,以减少细胞内该药物的积累,从而达到自我保护的目的。传统递送体系很难实现虾青素在体内的靶向释放和转运,使得其不能在特定的位点(结肠)进行释放和靶向吸收,导致虾青素在体内生物利用率一直处在较低的水平。从制剂方面考虑,普通的液态制剂的自微乳稳定性较低,携带和储存不方便,患者的顺应性差。
专利CN 104324020A公开了一种含有虾青素与白藜芦醇的自微乳颗粒制备方法提高了虾青素及白藜芦醇在水中的溶解度,提高了胃分散及肠道脂解的影响,同时生物有效利用度高。
专利CN 104352434A提供了一种高稳定性虾青素酯自微乳剂的制备方法,通过将一定比例的虾青素酯、载体油、稳定剂、乳化剂、助乳化剂和水相在特定的工艺条件下混合,然后经低压蒸馏脱除溶剂,最后制备得到高稳定性的虾青素酯自微乳剂。
专利CN 109985008A涉及一种虾青素固体自微乳及其制备方法,所述载体负载为虾青素,通过将虾青素、油脂、乳化剂、助乳化剂和固体吸附剂进行物理混合吸附,并在常温下制备得到虾青素固体自微乳。
P蛋白(P-glycoprotein,P-gp)是一种分子量为170ku的跨膜糖蛋白,P蛋白主要位于细胞膜,在胃肠道中分布并不均匀,从胃到结肠含量逐渐增加,胃部最低,空肠中等,结肠最高。研究表明,其在发挥转运功能时可形成转运蛋白-通道-受体复合物,调节ATP产生,使P蛋白利用ATP水解产生的能量将药物泵出细胞外。P蛋白发挥了外排泵的功能,将细胞内的药物逆浓度梯度转运至细胞外,因此降低了药物的生物利用度。采用P蛋白抑制剂能有效地解决外排作用从而提高其生物利用度。
经查阅,将虾青素与P蛋白联合使用制备成固体自微乳的方法在国内外均未报道。
发明内容
针对现有技术中虾青素水溶性差、液态自微乳制剂稳定性较低和体内生物利用度低等技术问题,本发明欲从影响生物利用度的角度P蛋白和载药体系的设计两方面着手考虑,设计出合理的P蛋白抑制剂-虾青素递送系统,以改善其应用特性。
本发明中的P蛋白抑制剂选取槲皮素。槲皮素是一种天然的多羟基黄酮类化合物,具有抗病毒、抗氧化、抗癌、抗炎、抗菌和心血管系统保护等多种药理作用,并且无致畸、致癌和致死的反应。与此同时,槲皮素也能够抑制药物代谢酶CYP3A4和药物转运蛋白P-糖蛋白的活性。但槲皮素与虾青素一样,在水中溶解度极低,口服吸收差、生物利用度低。
鉴于两者水溶性差、易氧化降解和生物利用率低等缺陷,本发明的首要目的是提供了一种含有虾青素和槲皮素的固体自微乳微囊。
本发明的第二个目的是提供了上述含有虾青素和槲皮素的固体自微乳微囊的制备方法,该方法得到的产品能有效地解决药物生物利用度差的问题,从而增加自微乳的稳定性。
本发明的第三个目的是提供了上述含有虾青素和槲皮素的固体自微乳微囊的应用。
为达到上述目的,本发明的解决方案是:
一种含有虾青素和槲皮素的固体自微乳微囊,其包括如下重量份的组分:
进一步地,虾青素为标准品,其纯度为98±1%。
进一步地,槲皮素的纯度为95±1%。
进一步地,油相选自肉桂油或蓖麻油中的一种以上。
进一步地,乳化剂选自吐温80、Cremophor RH 40或阿拉伯胶中的一种以上。
进一步地,助乳化剂选自聚乙二醇400或二乙二醇单乙基醚中的一种以上。
进一步地,固体吸附剂选自微晶纤维素、无水磷酸氢钙、硅酸镁铝、二氧化硅、阿拉伯树胶、柠檬酸异丙酯、甘露醇、PEG 6000或PEG 4000中的一种以上。
一种上述的含有虾青素和槲皮素的固体自微乳微囊的制备方法,其包括如下步骤:
(1)、将油相、乳化剂和助乳化剂混合,得到空白自微乳;
(2)、将槲皮素加入空白自微乳内,得到槲皮素自微乳;
(3)、将虾青素加入槲皮素自微乳内,搅拌得到含有虾青素和槲皮素的自微乳;
(4)、在含有虾青素和槲皮素的自微乳内加入固体吸附剂,混合得到含有虾青素和槲皮素的固体自微乳微囊。
进一步地,步骤(1)中,混合的温度为40-60℃,混合的时间为30-35min。
一种上述的含有虾青素和槲皮素的固体自微乳微囊作为载体系统在食品药品中的应用。
由于采用上述方案,本发明的有益效果是:
第一、本发明从载药递送体系设计角度出发,将虾青素与槲皮素两者结合制备固体自微乳微囊体系,从而突破虾青素的传统单运载体系,槲皮素具有很高的安全性,除用于食品抗氧化外,还可用作食用黄色素。有研究表明槲皮素在体内、体外一定浓度下均无急性毒性、致突变性、慢性或亚慢性毒性,能够抑制P-gp对药物的外排作用,从而抑制药物代谢酶CYP3A4和药物转运蛋白P-糖蛋白的活性,即采用具有P-gp抑制剂活性的药用辅料作为载体,制备P-gp底物的药物自微乳微囊载药体系,进一步提高生物利用度,同时提高了难溶于水的虾青素的溶解性,从而使得槲皮素与虾青素复配可以发挥协同增效的作用,不仅可以提高稳定性还能不影响虾青素的抗氧化能力,而且还提高了生物利用度,即槲皮素能提高虾青素的生物利用度,同时提高溶解度和抗氧化性。
第二、本发明将液态自微乳体系固体化可以克服液体自微乳的局限性,同时具有液态自微乳和固体制剂的优势,使药物的溶出度和生物利用度均得到提高。
第三、本发明的自微乳可作为中间体类型进一步制成胶囊、片剂和散剂等,用途广泛、适应性强,与食品配方复配使用,配伍性佳,可广泛用于食品及保健品领域;另外,加入固体吸附剂制成微囊在很大程度上增大了乳化液的稳定性,提高微囊化效率,并且可在一定环境条件下(如:口腔的咀嚼作用、消化道内酶的作用、胃肠蠕动和消化道内环境介质作用等)将芯材(虾青素与槲皮素)释放出来并发挥生物学功效,从而提高生物利用度。
第四、本发明采用溶剂蒸发法制备微囊可以将粒径固定在纳米级,既不需要升高温度也不需要引起相分离的凝聚剂,保证了虾青素与槲皮素的稳定性。
附图说明
图1为本发明的实施例1中空白自微乳的粒径分布示意图。
图2为本发明的实施例1中空白自微乳的Zeta电位分布示意图。
图3为本发明的实施例1中槲皮素自微乳的粒径分布示意图。
图4为本发明的实施例1中槲皮素自微乳20h后的粒径分布示意图。
图5为本发明的实施例1中虾青素-槲皮素自微乳的粒径分布示意图。
图6为本发明的实施例2中空白自微乳的粒径分布示意图。
图7为本发明的实施例2中槲皮素自微乳的粒径分布示意图。
图8为本发明的实施例2中空白自微乳的Zeta电位分布示意图。
图9为本发明的实施例2中虾青素-槲皮素自微乳的粒径分布示意图。
图10为本发明的实施例3中虾青素-槲皮素自微乳的粒径分布示意图。
图11为本发明的对比例1中虾青素-槲皮素自微乳的粒径分布示意图。
图12为本发明的对比例2中虾青素-槲皮素自微乳的粒径分布示意图。
具体实施方式
本发明提供了一种含有虾青素和槲皮素的固体自微乳微囊及其制备方法和应用。
<含有虾青素和槲皮素的固体自微乳微囊>
本发明的含有虾青素和槲皮素的固体自微乳微囊包括如下重量份的组分:
其中,虾青素为标准品,纯度为98±1%,购于上海阿拉丁生化科技股份有限公司。
槲皮素的纯度为95±1%,购于上海腾准生物科技有限公司。
油相选自肉桂油或蓖麻油中的一种以上,研究表明脂质链长度可调节纳米乳液的稳定性。长链脂肪酸脂质(13-21个碳原子)如蓖麻油、肉桂油等均可形成稳定的纳米乳剂从而提高物料在自微乳体系中的溶解性。
乳化剂选自吐温80、Cremophor RH 40或阿拉伯胶中的一种以上,它们均有较高的乳化效率,能自发形成水包油型(O/W型)、粒径小于100nm的微乳,其中Cremophor RH 40可降低多药耐药相关蛋白2的外排活性。
助乳化剂选自聚乙二醇(PEG)400或二乙二醇单乙基醚(Transcutol HP)中的一种以上,可调节乳化剂的亲水疏水平衡值,与乳化剂形成复合界面膜,从而形成稳定的微乳。
固体吸附剂选自微晶纤维素、无水磷酸氢钙、硅酸镁铝、二氧化硅、阿拉伯树胶、柠檬酸异丙酯、甘露醇、聚乙二醇(PEG)6000或聚乙二醇(PEG)4000中的一种以上,通过加入吸附剂或者固化材料,能使中间体系液体自微乳转变为固体制剂,从而解决了液态自微乳稳定性较低,携带和储存不方便等问题。
<含有虾青素和槲皮素的固体自微乳微囊的制备方法>
本发明的含有虾青素和槲皮素的固体自微乳微囊的制备方法包括如下步骤:
(1)、制备空白自微乳:称取20-40份油相、50-100份乳化剂和30-60份助乳化剂,待电磁搅拌均匀充分混合,得到透明微黄色的空白自微乳;
(2)、制备槲皮素自微乳:称取100-250份槲皮素加入上述的空白自微乳内,在60℃的恒温磁力搅拌下均匀混合,得到棕黄均一状的槲皮素自微乳;
(3)、制备虾青素-槲皮素自微乳:称取1-5份虾青素加入槲皮素自微乳内,在37℃恒温磁力搅拌,得到均一橙红色油状液体的含有虾青素和槲皮素的自微乳;
(4)、制备自微乳微囊载药体系:在含有虾青素和槲皮素的自微乳内加入固体吸附剂,混合乳化,充分均质,采用溶剂蒸发法使分散相挥发性溶剂从乳液体系中除去后,得到含有虾青素和槲皮素的固体自微乳,形成聚合物壳,用以制备微胶囊。
在步骤(1)中,混合的温度为40-60℃,混合的时间为30-35min。
除了采用上述方法制备含有虾青素和槲皮素的固体自微乳微囊,还可以采用下列方法:
方案一:用喷雾干燥技术将液态自微乳中加入固体吸附载体,混合均匀,再将其喷洒到热空气室中蒸发达到除去水分及其挥发性成分,形成干燥微粒制成微囊。
方案二:先制备自微乳将其用作壁材,将虾青素与槲皮素作为芯材,高压均质,喷雾干燥制得自微乳微囊。
方案三:采用同样活性作用的P蛋白抑制剂(紫杉醇、胡椒碱等)与虾青素配伍联用,从而制备自微乳载药体系。
用马尔文动态粒径电位分析仪测定自微乳水溶液粒径,Zeta电位评估体系的稳定性。即Zeta电位和粒径都是评价自微乳乳液稳定性的指标,Zeta电位表明纳米粒子的稳定性,反映其在介质中的分布状态,粒径分布反映其均匀性。纳米液滴表面的电荷较高(Zeta电位>±30mV)可防止液滴之间因强大的排斥力而产生聚集。
采用经典的评价抗氧化活性的方法ABTS自由基清除实验来评价有色抗氧化剂的活性,检测其生物利用度的指标。1,1-二苯基-2-三硝基苯肼(DPPH)和2,2-联氨-双(3-乙基苯并噻唑-6-磺酸)二胺盐(ABTS)自由基清除实验是基于分光光度法来测定样品的抗氧化活性,因ABTS测量波长在700nm附近存在吸收峰,有色氧化剂不容易产生光谱干扰,该方法具有操作简单、快速、重复性良好和易于标准化等优点。
虾青素体外清除自由基活性的研究。可通过与虾青素-槲皮素液体自微乳、虾青素-槲皮素自微乳微囊载药体系的对比实验,采用DPPH自由基测定法,利用DPPH·无水乙醇溶液在517nm处有紫色团的特征吸收峰,以分光光度法测定加入抗氧化剂后,在517nm处吸光值的下降表示其对DPPH自由基的清除能力来研究两体系在清除DPPH自由基(DPPH·)的能力。
<含有虾青素和槲皮素的固体自微乳微囊的应用>
本发明的含有虾青素和槲皮素的固体自微乳微囊作为载体系统可以在食品药品中得以应用。
以下结合实施例对本发明作进一步的说明。
实施例1:
本实施例的含有虾青素和槲皮素的固体自微乳微囊的制备方法包括如下步骤:
(1)、在25℃下,称取20份蓖麻油(作为油相)、20份吐温80(作为乳化剂)、30份Cremophor RH 40(作为乳化剂)和30份的PEG 400(作为助乳化剂),在60℃下,以400r/min的电磁搅拌均匀充分混合30min,得到微黄澄清均一的空白自微乳。
(2)、称取10份空白自微乳后,体系内少量多次加入100份槲皮素,在60℃的恒温磁力搅拌下均匀混合,得到黄色澄清均一、较为黏稠的槲皮素自微乳。
(3)、冷却至室温后,将3份虾青素加入槲皮素自微乳内,在37℃恒温磁力搅拌下,得到橙红色均一的含有虾青素和槲皮素的自微乳。
(4)、最后向含有虾青素和槲皮素的自微乳内加入难溶性载体材料硅酸镁铝(作为固体吸附剂),常温下进行物理混合吸附,充分均质,得到含有虾青素和槲皮素的固体自微乳微囊。
用马尔文动态粒径电位分析仪测得空白自微乳水溶液的粒径为53.48nm左右(如图1所示),电位为-7.69mV(如图2所示)。槲皮素自微乳水溶液的粒径为61.80nm左右(如图3所示),电位为-29.5mV。考虑药物分子上的亲水基团增加了药物分子的极性,会吸引更多非极性分子(如油性外壳),因此加入物料后体系的粒径比空白自微乳大。为了检测其体系的稳定性,25℃放置20h后再次检测槲皮素自微乳水溶液的平均粒径为48.45nm左右(如图4所示),其粒径变化无明显差异,显示其稳定性良好,且未发生乳液聚沉、絮凝等现象,重复性好。因此,本实施例的含有虾青素和槲皮素的固体自微乳微囊的稳定性好。
实施例2:
本实施例的含有虾青素和槲皮素的固体自微乳微囊的制备方法包括如下步骤:
(1)、在25℃下,称取20份蓖麻油(作为油相)、20份吐温80(作为乳化剂)、30份Cremophor RH 40(作为乳化剂)以及30份的Transcutol HP(作为助乳化剂),在60℃下,以400r/min的电磁搅拌均匀充分混合35min,得到微黄澄清均一、流动性好的空白自微乳。
(2)、称取10份空白自微乳后,体系内少量多次加入100份槲皮素,在60℃的恒温磁力搅拌下均匀混合,得到黄色澄清的槲皮素自微乳。
(3)、冷却至室温后,将3份虾青素加入槲皮素自微乳内,在37℃恒温磁力搅拌下,得到橙红色均一的含有虾青素和槲皮素的自微乳。
(4)、最后向含有虾青素和槲皮素的自微乳内加入水溶性载体材料甘露醇、PEG6000和PEG 4000(作为固体吸附剂),常温下进行物理混合吸附,充分均质,得到含有虾青素和槲皮素的固体自微乳微囊。
用马尔文动态粒径电位分析仪测得空白自微乳水溶液的粒径为125.7nm左右(如图6所示),电位为-12.6mV(如图8所示)。槲皮素自微乳水溶液的粒径为138.2nm左右(如图7所示)。考虑药物分子上的亲水基团增加了药物分子的极性,会吸引更多非极性分子(如油性外壳),因此加入物料后体系的粒径比空白自微乳大。
按照实施例1和实施例2步骤制备虾青素-槲皮素液体自微乳,便于和其他固体自微乳体系作对照实验。用马尔文动态粒径电位分析仪测得实施例1的虾青素-槲皮素自微乳(助乳化剂为PEG 400)水溶液的粒径为57.84nm(如图5所示)左右,实施例2的虾青素-槲皮素自微乳(助乳化剂为Transcutol HP)的水溶液粒径为143.2nm(如图9所示)左右。从宏观上看,前者流动性较小,较黏稠,液体颜色也较深。从微观上看,两者除助乳化剂不同,其余实验条件保持相同情况下,前者粒径明显小于后者,说明助乳化剂为PEG 400构成的液体自微乳更加稳定。
实施例3:
本实施例的含有虾青素和槲皮素的固体自微乳微囊的制备方法包括如下步骤:
(1)、在25℃下,称取20份肉桂油(作为油相)、20份吐温80(作为乳化剂)、30份Cremophor RH 40(作为乳化剂)和30份的PEG 400(作为助乳化剂),在60℃下,以400r/min的电磁搅拌均匀充分混合30min,得到亮黄色澄清的空白自微乳。
(2)、称取10份空白自微乳后,体系内少量多次加入100份槲皮素,搅拌均匀后,得到黄色均一的槲皮素自微乳。
(3)、冷却至室温后,将3份虾青素加入槲皮素自微乳内,在37℃恒温磁力搅拌下,得到橙红色均一的含有虾青素和槲皮素的自微乳。
(4)、最后向含有虾青素和槲皮素的自微乳内加入难溶性载体材料无水磷酸氢钙(作为固体吸附剂),常温下进行物理混合吸附,充分均质,得到含有虾青素和槲皮素的固体自微乳微囊。
与实施例1对比:在制备含有虾青素和槲皮素液体自微乳,除所加油相不同其余成分均相同,用马尔文动态粒径电位分析仪测得实施例3的虾青素-槲皮素自微乳(助乳化剂为PEG400)水溶液的平均粒径为155.4nm(如图10所示)左右,与实施例1的虾青素-槲皮素自微乳(助乳化剂为PEG 400)水溶液的粒径为57.84nm左右相差较大。从宏观上看,后者流动性较小,较黏稠,液体颜色也较深。从微观上看,两者除油相不同,其余实验条件保持相同情况下,前者粒径明显小于后者,说明油相为蓖麻油构成的液体自微乳更加稳定。
实施例4:
本实施例的含有虾青素和槲皮素的固体自微乳微囊的制备方法包括如下步骤:
(1)、在25℃下,称取20份蓖麻油(作为油相)和3份虾青素,将虾青素和蓖麻油混合搅拌至大部分虾青素溶解到蓖麻油中,形成体系的油相;
(2)、先将20份吐温80(作为乳化剂)和30份Cremophor RH 40(作为乳化剂)在60℃恒温水浴中搅拌均匀后,加入到30份的Transcutol HP(作为助乳化剂)中,再在60℃的恒温磁力搅拌下充分混合形成均一相。
(3)、在上述(2)体系中少量多次加入100份槲皮素,在60℃下,以400r/min的电磁搅拌均匀充分混合30min。
(4)、待上述(3)体系冷却至室温后加入上述(1)的油相,再在37℃恒温磁力搅拌直至橙红色均一的含有虾青素和槲皮素的自微乳。
(5)、最后向含有虾青素和槲皮素的自微乳内加入难溶性载体材料20份二氧化硅(作为固体吸附剂),常温下进行物理混合吸附,混合均匀,得到虾青素固体自微乳。
本实施例与其他实施例相比,加入物料的顺序不同不会影响其自微乳的稳定性,因虾青素具有脂溶性,将其先溶于油相再与其它两相混合制备自微乳,能便于更好得溶解在体系中,增大其溶解度。
对比例1:
本对比例的含有虾青素和槲皮素的固体自微乳微囊的制备方法包括如下步骤:
(1)、在25℃下,称取20份蓖麻油(作为油相)、20份吐温80(作为乳化剂)、30份Cremophor RH 40(作为乳化剂)以及30份的PEG 400(作为助乳化剂),在60℃下,以400r/min的电磁搅拌均匀充分混合30min,得到微黄澄清均一、流动性好的空白自微乳。
(2)、称取10份空白自微乳后,体系内少量多次加入3份槲皮素,在60℃的恒温磁力搅拌下均匀混合,得到淡黄色澄清的槲皮素自微乳。
(3)、冷却至室温后,将300份虾青素加入槲皮素自微乳内,在37℃恒温磁力搅拌下,得到深红色均一的含有虾青素和槲皮素的自微乳。
(4)、最后向含有虾青素和槲皮素的自微乳内加入难溶性载体材料微晶纤维素(作为固体吸附剂),常温下进行物理混合吸附,充分均质,得到含有虾青素和槲皮素的固体自微乳微囊。
用马尔文动态粒径电位分析仪测得对比例1的虾青素-槲皮素自微乳(助乳化剂为PEG400)水溶液的平均粒径为79.74nm(如图11所示)左右。但经过72h后发现有明显的乳液分层现象,稳定性较差且该实施例所用虾青素含量较多,耗材较大。因此,实施例1的含有虾青素和槲皮素的固体自微乳微囊的稳定性更好。
对比例2:
本对比例的含有虾青素和槲皮素的固体自微乳微囊的制备方法包括如下步骤:
(1)、在25℃下,称取20份蓖麻油(作为油相)、20份吐温80(作为乳化剂)、30份Cremophor RH 40(作为乳化剂)以及30份的PEG 400(作为助乳化剂),在60℃下,以400r/min的电磁搅拌均匀充分混合30min,得到微黄澄清均一、流动性好的空白自微乳。
(2)、称取10份空白自微乳后,体系内少量多次加入300份槲皮素,在60℃的恒温磁力搅拌下均匀混合,得到亮黄色澄清的槲皮素自微乳。
(3)、冷却至室温后,将0.03份虾青素加入槲皮素自微乳内,在37℃恒温磁力搅拌下,得到浅红色均一的含有虾青素和槲皮素的自微乳。
(4)、最后向含有虾青素和槲皮素的自微乳内加入难溶性载体材料微晶纤维素(作为固体吸附剂),常温下进行物理混合吸附,充分均质,得到含有虾青素和槲皮素的固体自微乳微囊。
用马尔文动态粒径电位分析仪测得对比例2的虾青素-槲皮素自微乳(助乳化剂为PEG400)水溶液的平均粒径为45.69nm(如图12所示)左右。但经过72h后发现有轻微的乳液分层、絮凝等现象,稳定性较差,且虾青素含量过少,功能性与实施例1相比也大大下降。因此,实施例1的含有虾青素和槲皮素的固体自微乳微囊的稳定性好。
上述对实施例的描述是为了便于该技术领域的普通技术人员能理解和使用本发明。熟悉本领域技术人员显然可以容易的对这些实施例做出各种修改,并把在此说明的一般原理应用到其他实施例中,而不必经过创造性的劳动。因此,本发明不限于上述实施例。本领域技术人员根据本发明的原理,不脱离本发明的范畴所做出的改进和修改都应该在本发明的保护范围之内。
Claims (10)
2.根据权利要求1所述的固体自微乳微囊,其特征在于:所述虾青素的纯度为98±1%。
3.根据权利要求1所述的固体自微乳微囊,其特征在于:所述槲皮素的纯度为95±1%。
4.根据权利要求1所述的固体自微乳微囊,其特征在于:所述油相选自肉桂油或蓖麻油中的一种以上。
5.根据权利要求1所述的固体自微乳微囊,其特征在于:所述乳化剂选自吐温80、聚氧乙烯氢化蓖麻油40或阿拉伯胶中的一种以上。
6.根据权利要求1所述的固体自微乳微囊,其特征在于:所述助乳化剂选自聚乙二醇400或二乙二醇单乙基醚中的一种以上。
7.根据权利要求1所述的固体自微乳微囊,其特征在于:所述固体吸附剂选自微晶纤维素、无水磷酸氢钙、硅酸镁铝、二氧化硅、阿拉伯树胶、柠檬酸异丙酯、甘露醇、聚乙二醇6000或聚乙二醇4000中的一种以上。
8.一种根据权利要求1-7任一项所述的含有虾青素和槲皮素的固体自微乳微囊的制备方法,其特征在于:其包括如下步骤:
(1)、将油相、乳化剂和助乳化剂混合,得到空白自微乳;
(2)、将槲皮素加入所述空白自微乳内,得到槲皮素自微乳;
(3)、将虾青素加入所述槲皮素自微乳内,搅拌得到含有虾青素和槲皮素的自微乳;
(4)、在所述含有虾青素和槲皮素的自微乳内加入固体吸附剂,混合得到含有虾青素和槲皮素的固体自微乳微囊。
9.根据权利要求8所述的制备方法,其特征在于:步骤(1)中,所述混合的温度为40-60℃,所述混合的时间为30-35min。
10.一种根据权利要求1-7任一项所述的含有虾青素和槲皮素的固体自微乳微囊作为载体系统在食品药品中的应用。
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CN114081868B (zh) * | 2021-10-20 | 2023-08-22 | 江苏大学 | 静电喷雾法制备的香叶木素固体自微乳纳米粒及制备方法 |
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