CN117257989A - 一种聚环糊精基儿茶素类纳米递送系统及应用 - Google Patents
一种聚环糊精基儿茶素类纳米递送系统及应用 Download PDFInfo
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- CN117257989A CN117257989A CN202311339397.2A CN202311339397A CN117257989A CN 117257989 A CN117257989 A CN 117257989A CN 202311339397 A CN202311339397 A CN 202311339397A CN 117257989 A CN117257989 A CN 117257989A
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- Prior art keywords
- catechin
- polycyclodextrin
- delivery system
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- cyclodextrin
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Classifications
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- A—HUMAN NECESSITIES
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- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
- A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline
- A61K31/353—3,4-Dihydrobenzopyrans, e.g. chroman, catechin
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
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Abstract
本发明属于生物医用纳米材料技术领域,涉及一种聚环糊精基儿茶素类纳米递送系统及应用。该纳米递送体系的制备方法,包括以下步骤:(1)将环糊精与环氧氯丙烷反应得到聚环糊精(PCD),再将儿茶素类提取物包合在聚环糊精中得到PCD@儿茶素纳米粒子;(2)将N‑乙酰半胱氨酸接枝到壳聚糖上得到巯基化壳聚糖(CS);(3)将上述PCD@儿茶素和CS混合,得到CS/PCD@儿茶素,即为上述纳米递送系统。本发明提供的CS/PCD@儿茶素类纳米递送系统可在鼻腔内环境中持续释放儿茶素类分子,从而改善鼻炎症状,可以有效地治疗变应性鼻炎。本发明具有制备方法简单、绿色、经济,提高了药物治疗变应性鼻炎的效果,在生物医药领域具备较大的应用价值。
Description
技术领域
本发明属于生物医用纳米材料领域,尤其涉及一种聚环糊精基儿茶素类纳米递送系统及应用。
背景技术
过敏性鼻炎(allergic rhinitis,AR),也称为变应性鼻炎,是一种常见的鼻粘膜炎性疾病。AR主要是由于过敏原暴露所致的由免疫球蛋白E(IgE)介导的Ⅰ型超敏反应驱动。临床症状包括阵发性喷嚏、清水样涕、鼻痒和鼻塞等,严重情况下会导致睡眠障碍、抑郁、哮喘、鼻咽癌等多种并发症,这严重降低了人们的生活和工作质量。虽然抗组胺药、糖皮质激素、白三烯受体拮抗剂等多种药物被广泛应用于AR的治疗,但长期使用这些药物对于AR的治疗效果十分有限。首先在鼻内微环境中,由于微酸性环境,鼻纤毛运动和溶菌酶的存在,使得小分子药物很难在鼻腔内长时间治疗,达不到应有的治疗效果,所以需要每天多次给药维持,不可避免的对鼻内粘膜产生刺激。其次,许多药物具有耐受性,长期频繁使用对AR的治疗效果欠佳。更重要的是,抗组胺药、糖皮质激素等药物的长期使用会对身体产生诸多不良副作用。
公开号CN115957345A的专利:一种用于变应性鼻炎治疗的pH响应性靶向纳米递送系统及其制备方法和应用,针对以往变应性鼻炎喷剂治疗效果不佳、反复治疗容易造成的鼻黏膜损伤这一现状,研发制备了一种pH响应性靶向纳米递送系统CaCO3@MP-Flu@DHLA,将其用于变应性鼻炎治疗,可以提高变应性鼻炎的治疗效果。但是该方法中使用的糖皮质激素药物长期使用具有非常多的副作用,且抗组胺药长期使用也有药物耐受性的问题,需增加药量才能达到原有效果。
因此,迫切需开发一种更加天然长效的治疗手段来治疗变应性鼻炎。
儿茶素类化合物是绿茶中的主要成分,也是一类生物活性很高的多酚。儿茶素具有抗炎症、抗菌、抗病毒及抗氧化等效用,近年来有许多报道证明儿茶素可通过调节相关酶活性,具有显著的抗过敏作用(International Immunopharmacology,2018,61,241-248,Food Science and Human Wellness,2023,12,882-888)。但由于儿茶素存在脂溶性低、稳定性差、在人体内利用率低等缺点,很大程度限制了儿茶素类化合物在人体,特别是鼻腔中的应用。
研究人员通过酶法、化学法、微生物法等对儿茶素类化合物进行结构修饰以提高其药效及生物利用率。例如,研究表明:γ-环糊精可以和儿茶素中的表没食子儿茶素没食子酸酯(EGCG)产生包合,并增加EGCG的溶解度,继而用于溃疡性结肠炎的治疗(Foodchemistry,2023,418,136000-136000)。但需要注意的是,这类儿茶素衍生物均不具备生物粘附性能,在鼻腔内的停留时间很短,不适合应用于鼻腔内。随着生物医学领域的发展,新型递送系统逐渐进入人们的视野,尤其是其可以保护活性成分免受降解,增强生理稳定性,控释药物,改善生物分布,已越来越受到人们的关注,成为新兴的重要研究领域。近年来在已报道儿茶素类纳米递送体系中,包括将儿茶素包合在β-乳球蛋白颗粒或者透明质酸水凝胶中(3Biotech.,2019,9,6),或将EGCG装载到一种新型的双亲水性超分子超分支聚酰胺-右旋糖酐偶联物中(NewJ.Chem.,2018,42,19600-19607),都显著增强了儿茶素的稳定性和抗炎抗氧化能力,明显提高了儿茶素的生物利用度。但是针对鼻内特定部位的递送治疗系统,需要有合适的粒径、电荷和粘附性能,才能使得体系能够有效的滞留在鼻粘膜部位,防止被酶作用和鼻纤毛运动稀释或清除。此外,递送系统需要有良好的透皮性能,能使药物在鼻粘膜部位被有效吸收,从而发挥显著的治疗效果。而现有的儿茶素类递送系统直接通过静脉或口服进入人体,不具备上述特性,但是静脉或者口服给药不能快速见效,因此现阶段缺乏对鼻内特定部位的递送治疗研究。
综上所述,现有技术存在的问题是:
1、现有的天然绿色治疗手段的儿茶素类纳米递送体系中没有针对鼻内特定部位的递送治疗系统,只有静脉或者口服给药,见效慢。
2、现有针对鼻内特定部位的递送治疗系统,虽然比静脉或者口服给药效果快,但是生物安全性相对较差,对人体会产生一定毒性作用,并且该方法中糖皮质激素药物长期使用具有非常多的副作用,且抗组胺药长期使用也有药物耐受性的问题,需增加药量才能达到原有效果。
发明内容
针对现有技术存在的问题,本发明提供了一种聚环糊精基儿茶素类纳米递送系统及应用,以解决上述现有技术存在的问题。
一种聚环糊精基儿茶素类纳米递送系统,将环糊精与环氧氯丙烷交联形成具有纳米结构的聚环糊精,通过环糊精的空腔结构将儿茶素包合在其中;再将巯基壳聚糖加入到儿茶素聚环糊精体系中,大幅度增加其在鼻腔内的粘附性。使整个纳米递送系统不仅可以保护儿茶素,阻止其快速分散,同时又能逐步释放儿茶素,达到持续治疗的效果。
为实现上述目的,本发明提供了如下方案:
一种聚环糊精基儿茶素类纳米递送系统,其制备方法包括以下步骤:
步骤(1)、将环糊精与环氧氯丙烷反应得到聚环糊精,再将儿茶素类化合物包合在聚环糊精中得到聚环糊精@儿茶素纳米粒子;
步骤(2)、将N-乙酰半胱氨酸接枝到壳聚糖上得到巯基化壳聚糖;
步骤(3)、将步骤(1)得到的聚环糊精@儿茶素纳米粒子和步骤(2)得到的巯基化壳聚糖混合,即为聚环糊精基儿茶素类纳米递送系统。
进一步地,步骤(1)中的环糊精为α-环糊精,β-环糊精,γ-环糊精,及以上三种环糊精的衍生物中的任意一种,其中,优选β-环糊精或β-环糊精的衍生物。因为β-环糊精及其衍生物相较于其它环糊精,其空腔体积和儿茶素类的药物的分子体积接近,具备最佳的包合效果。
进一步地,步骤(1)中的儿茶素类化合物包括儿茶素(catechin,C)、表儿茶素(epicatechin,EC)、没食子儿茶素(gallocatechin,GC)、表没食子儿茶素(epigallocatechin,EGC)、儿茶素没食子酸酯(catechin gallate,CG)、表儿茶素没食子酸酯(epicatechin gallate,ECG)、没食子儿茶素没食子酸酯(gallocatechin gallate,GCG)及表没食子儿茶素没食子酸酯(epigallocatechin gallate,EGCG)中的一种或几种。
进一步地,在步骤(1)中的环糊精与环氧氯丙烷反应得到聚环糊精的步骤包括:将环糊精溶解于氢氧化钠溶液中搅拌,加入环氧氯丙烷进行聚合反应,随后将混合溶液在异丙醇中沉淀,然后在沉淀中加入盐酸调节pH至中性,最后沉淀经透析冻干得到聚环糊精(PCD);所述环糊精和环氧氯丙烷的摩尔比为1:8-1:20;氢氧化钠质量浓度为15-30%(w/v),搅拌条件为25-60℃搅拌1-4h;聚合条件为25-50℃搅拌1-5h;盐酸浓度为3-8M;透析袋截留分子量8000-14000,透析时间3d。
进一步地,步骤(1)中的儿茶素类化合物包合在聚环糊精中的步骤包括:将PCD和儿茶素类化合物分别溶解于去离子水中搅拌,然后将混合溶液经透析冻干得到PCD@儿茶素纳米粒子;所述搅拌条件为:15-30℃、搅拌6-24h;透析袋截留分子量1000,透析时间3d。
进一步地,步骤(2)具体包括:将N-乙酰半胱氨酸溶解于DMF溶液中,加入1-乙基-(3-二甲基氨基丙基)碳化二亚胺盐酸盐(EDC盐酸)和1-羟基苯并三唑(HOBT)搅拌得到N-乙酰半胱氨酸溶液;将100-400mpa.s粘度壳聚糖溶解于盐酸溶液中,得到壳聚糖溶液;将N-乙酰半胱氨酸溶液滴入壳聚糖溶液中,加入氢氧化钠调节pH至5.0后继续搅拌得到混合溶液,将混合溶液经过透析冻干得到巯基化壳聚糖(CS);所述N-乙酰半胱氨酸、EDC盐酸、HOBT和壳聚糖的摩尔比为4:1:1:4;N-乙酰半胱氨酸溶液搅拌条件为25℃搅拌1-3h;盐酸质量分数为15-30%(w/v);壳聚糖溶液质量分数0.5-2%(w/v);混合溶液搅拌条件为25℃避光搅拌1-3h;透析条件为i:5mmol/L盐酸溶液,12h,2次;ii:5mmol/L盐酸和1%氯化钠溶液,12h,2次;iii:1mmol/L盐酸溶液,12h,2次;透析袋截留分子量8000-14000,透析时间3d。
进一步地,步骤(3)中PCD@儿茶素和CS的混合得到CS/PCD@儿茶素的步骤包括:将PCD@儿茶素和CS分别溶解于去离子水中充分搅拌,冻干,得到CS/PCD@儿茶素;所述PCD@儿茶素和CS的质量比为1:5-5:1。所述搅拌条件为25℃搅拌3-8h。
进一步地,上述的制备方法制备得到的儿茶素类纳米递送系统,纳米粒子粒径在50-800nm。
本发明还提供上述儿茶素类纳米递送系统在治疗变应性鼻炎中的应用,包括在治疗变应性鼻炎的药物上的应用。
进一步的,上述应用还包括在药学上可接受的辅料方面的应用。
本发明的有益效果:
(1)本发明提供的聚环糊精基儿茶素类纳米递送系统制备简易、条件容易控制、原料皆为常见易购材料,成本低廉,并且无毒副作用。
(2)本发明提供的聚环糊精基儿茶素类纳米递送系统对儿茶素进行包合后,一方面提高了药物分子长期储存的稳定性,另一方面合适的粒径和电位使得纳米递送系统适用于鼻内给药。避免了需要多次给药,对鼻内粘膜产生的刺激。
(3)本发明提供的聚环糊精基儿茶素类纳米递送系统,在体外实验证明,CS/PCD@儿茶素在鼻内环境中能够持续释放,避免了需要多次给药,对鼻内粘膜产生的刺激,并且相较于单独的儿茶素,在鼻粘膜部位滞留量更高;在体内实验中证明,CS/PCD@儿茶素能够比单独儿茶素更加有效缓解变应性鼻炎小鼠的过敏症状,可以实现对变应性鼻炎疾病的有效治疗。
附图说明
图1是本发明提供的聚环糊精基儿茶素类纳米递送系统合成示意图;
图2是本发明提供的不同测试例粘附性测定曲线图。
具体实施方式
下面将对本发明实施例中的技术方案进行清楚、完整地描述。所描述的实施例仅仅是本发明一部分实施例,而不是全部的实施例。基于本发明中的实施例,本领域普通技术人员在没有作出创造性劳动前提下所获得的所有其它实施例,都属于本发明保护的范围。
本发明中提到的PCD:聚环糊精,CS:巯基化壳聚糖,EGCG:表没食子儿茶素没食子酸酯,ECG:表儿茶素没食子酸酯,EGC:表没食子儿茶素。
如下的实施例可以参照如图1所示的合成方式制备聚环糊精基儿茶素类纳米递送系统。
实施例1:
(1)聚环糊精包合物的制备方法
将16gα-CD加入16mL 22%(w/v)氢氧化钠溶液中,在50℃搅拌2h。然后,加入22mL环氧氯丙烷,再搅拌4h。随后将混合溶液滴到400mL异丙醇中沉淀,并放置20分钟。倒出上清液,加入6M盐酸,调节沉淀物pH至中性。最后,沉淀装入透析袋(MW=8000-14000)中透析3d,通过冷冻干燥获得聚环糊精白色粉末(PαCD)。将36mg PαCD和10mg GCG在去离子水中溶解并搅拌12h。然后,将混合溶液装入透析袋(MW=1000)中透析3d,通过冷冻干燥获得聚环糊精包合物白色粉末(PαCD@GCG)。(2)巯基化壳聚糖的制备方法
将5gN-乙酰半胱氨酸分别溶解在10mL DMF溶剂中,加入1.3g EDC盐酸和0.9gHOBT,并在25℃下搅拌3h,激活NAC的羧基得到N-乙酰半胱氨酸溶液。将200-400mpa.s粘度的1g壳聚糖溶解于80mL的20%(w/v)盐酸溶液中,得到1.25%的壳聚糖溶液。将N-乙酰半胱氨酸溶液以1:1的摩尔比滴入壳聚糖溶液中。然后通过加入氢氧化钠(1M)将pH调整到5.0,并在25℃黑暗中搅拌3h得到混合溶液。将混合溶液在黑暗条件下用透析袋(MW=8000-14000)透析,顺序如下:i在5mmol/L氯化氢溶液中透析2次12h;ⅱ在5mmol/L氯化氢溶液和1%氯化钠溶液中透析2次,每次12h;ⅲ在1mmol/L氯化氢溶液中透析2次,每次12h。透析后,将溶液冷冻干燥得到巯基壳聚糖微黄色粉末(CS)。
(3)纳米递送体系的制备
取50mg步骤(1)制得的PαCD@GCG包合物溶解在10mL水中,加入10mg步骤(2)制得的CS溶解在10mL水中,在25℃搅拌6h,冻溶液冷冻干燥得到纳米递送体系(CS/PαCD@GCG)。
实施例2:
(1)聚环糊精包合物的制备方法
将20gβ-CD加入20mL25%(w/v)氢氧化钠溶液中,在50℃搅拌2h。然后,加入22mL环氧氯丙烷,再搅拌4h。随后将混合溶液滴沉淀到500mL异丙醇中,并放置20分钟。倒出上清液,加入6M盐酸,调节沉淀物pH至中性。最后,沉淀装入透析袋(MW=8000-14000)中透析3d,通过冷冻干燥获得聚环糊精白色粉末(PβCD)。将40mg PβCD和10mg GCG在去离子水中溶解并搅拌12h。然后,将混合溶液装入透析袋(MW=1000)中透析3d,通过冷冻干燥获得聚环糊精包合物白色粉末(PβCD@GCG)。(2)巯基化壳聚糖的制备方法
与实施例1步骤(2)不同的是N-乙酰半胱氨酸是4.5g,DMF溶剂是8mL,HOBT是0.93g,壳聚糖的粘度为100-200mpa.s。
(3)纳米递送体系的制备
取30mg步骤(1)制得的PβCD@GCG包合物溶解在10mL水中,加入10mg步骤(2)制得的CS溶解在10mL水中,在25℃搅拌6h,冻溶液冷冻干燥得到纳米递送体系(CS/PβCD@GCG)。
实施例3:
(1)聚环糊精包合物的制备方法
将25gγ-CD加入25mL 30%(w/v)氢氧化钠溶液中,在50℃搅拌2h。然后,加入25mL环氧氯丙烷,再搅拌4h。随后将混合溶液滴沉淀到500mL异丙醇中,并放置20分钟。倒出上清液,加入6M盐酸,调节沉淀物pH至中性。最后,沉淀装入透析袋(MW=8000-14000)中透析3d,通过冷冻干燥获得聚环糊精白色粉末(PγCD)。将43mg PγCD和5mg的EGC和5mg的EGCG在去离子水中溶解并搅拌12h。然后,将混合溶液装入透析袋(MW=1000)中透析3d,通过冷冻干燥获得聚环糊精包合物白色粉末(PγCD@EGC+EGCG)。
(2)巯基化壳聚糖的制备方法
与实施例1步骤(2)不同的是N-乙酰半胱氨酸是4.5g,DMF溶剂是8mL,HOBT是0.95g,壳聚糖的粘度为100-200mpa.s。
(3)纳米递送体系的制备
取10mg步骤(1)制得的PγCD@EGC包合物溶解在10mL水中,加入10mg步骤(2)制得的CS溶解在10mL水中,在25℃搅拌6h,冻溶液冷冻干燥得到纳米递送体系(CS/PγCD@EGC+EGCG)。
对比例1
对比例1与实施例1不同的是:仅制备PαCD@GCG包合物纳米粒,不加入CS。
对比例2
对比例1与实施例1不同的是:为αCD+GCG的包合物+CS,未制成纳米粒子。
(一)纳米递送系统的粒径和Zeta电位测试
表1实施例纳米递送系统的粒径和Zeta电位表
表1粒径和电位测试表明,实施例1、实施例2、实施例3粒径均为纳米级,相较于环糊精单质,由于聚环糊精形成了纳米结构,具有比表面积高,靶向性好的优点,并有效延长体内循环时间。电位均带正电荷,使其形成的物质具有更好的粘附性。
(二)粘附性测定
将亲水膜(硝酸纤维素膜,孔径0.45μm孔径)浸泡在粘蛋白水溶液(0.1%猪胃粘蛋白,Ⅱ型)中浸泡2h。随后,取出膜,并在膜上滴下100μL的如下表2中的测试样品溶液。1min后,用PBS溶液(磷酸盐缓冲溶液)以1mL/min的流速冲洗10min。最后,用乙醇洗涤膜上的残留GCG,用紫外-可见分光光度法测定不同给药体系中的药物残留。结果如表2和图2所示:
表2药物滞留量表
从药物滞留量表中GCG和对比例1及对比例2相比可知,没有形成纳米粒子或不加入CS,的样品,最后测得的药物滞留量远远低于用聚环糊精包合儿茶素的测试样品溶液最后测得的药物滞留量。
从图2可知,相较于GCG和对比例1,纳米递送系统(实施例1,实施例2,实施例3)在模拟鼻腔内环境中的滞留量明显增强,实施例3>实施例2>实施例1,在实施例2后增长速率明显变小。结果显示单一使用聚环糊精其粘附性较低,加入巯基化壳聚糖后,粘附性显著提高。说明滞留时间与CS的加入量呈正相关关系。在实施例1、实施例2、实施例3整个体系中,巯基化壳聚糖在体系中的质量占比分别为17%、25%、50%,从实施例1、实施例2、实施例3对比中可以看出,巯基化壳聚糖含量在25%以上后,对递送体系粘附率的提升较小。在固定给药剂量的情况下,如果巯基化壳聚糖含量较高,那么递送体系中药物总含量就会降低。所以为了达到一个优异的粘附效果和一个较高药物含量,需要有一个药物和材料合适的加入平衡比。实施例2中巯基化壳聚糖质量占比为25%时效果较佳。
(三)释放测定
将实施例2的CS/PβCD@GCG(2mL,2.67mg/mL)放置在透析袋(MW=3500)中,将袋子浸泡在PBS溶液(pH 5.5,20mL)中。然后将它们放在33℃的摇晃水浴中培养。每隔24h,取出2mL的透析培养基进行测量,用相同体积的新鲜培养基代替。采用紫外-可见分光光度法测定儿茶素的含量,计算药物累积释放量。结果如表3所示:
表3纳米递送系统的累积释放量表
从药物累积释放量表结果可知,实施例2中儿茶素能够长时间持续释放。
鼻腔内环境呈微酸性,CS在微酸性环境中其氨基的质子化使得体系逐步崩解,逐步释放出PCD纳米粒,纳米粒也会在该环境中逐步释放出包合的药物,以达到阻止儿茶素快速分散,又能逐步释放药物的作用,起到持续治疗的效果。而单独的儿茶素在鼻粘膜的部位会快速分散,部分药物未产生药效就被排出,不能起到持续的治疗效果。
(四)稳定性测定
将GCG(2.4mg)、对比例1PαCD@GCG(24mg)和实施例2CS/PβCD@GCG(32mg)分别溶解在pH 7.0的24mL去离子水中。将上述样品溶液分别放置于37℃药物稳定性试验室中。然后,待30天后吸取样品溶液,离心,用0.45μm滤膜过滤上清液,用紫外-可见分光光度法测定GCG的含量。结果如表4所示:
表4纳米递送系统的药物保留量表
从药物稳定保留量表结果可知,实施例2相较于单独的药物,在模拟鼻腔内温度下能够明显保护儿茶素类药物的降解速率,使得药物的稳定性显著提高。
(五)变应性鼻炎治疗效果的研究
动物:BALB/c小鼠(18-22g,6-8周)购自成都达硕实验动物有限公司(许可证编号:SCXK(川)2020-030,自有给予水和实物。
药效学研究:所有小鼠分为5组:空白对照组、模型组、布地奈德组、GCG组、对比例1组、实施例2组(每组n=6只)。除空白对照组外,其余各组小鼠在每隔一天腹腔注射0.1mL(含卵清蛋白50μg和Al(OH)31mg)生理盐水,每2天注射1次,共7次,第一次注射日期设为第1天。第15天,每个鼻孔给予10%OVA(50μL),每日1次,共10次,空白对照组小鼠单独给予生理盐水。开始鼻内OVA给药后,每4日给小鼠鼻腔两侧给予50μL布地奈德(20μg/kg)、GCG(100μg/kg)、对比例1(10mg/kg)、实施例2(13mg/kg)共5次。
为了评估鼻炎症状的缓解情况,在第35天将小鼠放入观察笼中约15min进行适应。然后,将50μL的10%OVA溶液滴入小鼠的双侧鼻腔中。刺激30分钟后,在10min期间计算打喷嚏和挠鼻的频率。使用三个盲测试者的测量平均值进行统计分析。结果如表5所示:
表5各组小鼠打喷嚏和挠鼻次数
从变应性鼻炎小鼠的疗效结果可知,实施例2显著降低了小鼠打喷嚏和挠鼻的次数,并且明显优于单独GCG和常用药物抗过敏药物布地奈德,说明儿茶素类纳米递送系统可以改善鼻炎症状,有效地治疗变应性鼻炎。
以上所述仅为本发明的较佳实施例而已,并不用以限制本发明,凡在本发明的精神和原则之内所作的任何修改、等同替换和改进等,均应包含在本发明的保护范围之内。
Claims (9)
1.一种聚环糊精基儿茶素类纳米递送系统,其特征在于,其制备方法包括以下步骤:
步骤(1)、将环糊精与环氧氯丙烷反应得到聚环糊精,再将儿茶素类化合物包合在聚环糊精中得到聚环糊精@儿茶素纳米粒子;
步骤(2)、将N-乙酰半胱氨酸接枝到壳聚糖上得到巯基化壳聚糖;
步骤(3)、将步骤(1)得到的聚环糊精@儿茶素纳米粒子和步骤(2)得到的巯基化壳聚糖混合,即为聚环糊精基儿茶素类纳米递送系统。
2.根据权利要求1所述的一种聚环糊精基儿茶素类纳米递送系统,其特征在于,所述步骤(1)中的环糊精为α-环糊精、β-环糊精、γ-环糊精及以上三种环糊精的衍生物中的任意一种。
3.根据权利要求2所述的一种聚环糊精基儿茶素类纳米递送系统,其特征在于,所述步骤(1)中的环糊精为β-环糊精或β-环糊精的衍生物。
4.根据权利要求1所述的一种聚环糊精基儿茶素类纳米递送系统,其特征在于,所述步骤(1)中的儿茶素类化合物为表没食子儿茶素、表儿茶素没食子酸酯、表没食子儿茶素没食子酸酯中的任意一种或两种。
5.根据权利要求1所述的一种聚环糊精基儿茶素类纳米递送系统,其特征在于,所述巯基化壳聚糖在聚环糊精基儿茶素类纳米递送系统中的质量占比为17%-50%。
6.根据权利要求1所述的一种聚环糊精基儿茶素类纳米递送系统,其特征在于,所述巯基化壳聚糖在聚环糊精基儿茶素类纳米递送系统中的质量占比为25%。
7.根据权利要求1所述的一种聚环糊精基儿茶素类纳米递送系统,其特征在于,所述步骤(1)中的环糊精和环氧氯丙烷的摩尔比为1:8-1:20;步骤(3)中PCD@儿茶素和CS的质量比为1:5-5:1。
8.根据权利要求1所述的一种聚环糊精基儿茶素类纳米递送系统,其特征在于,所述步骤(2)中壳聚糖的粘度为100-400mpa.s。
9.一种根据权利要求1-8中任意一项权利要求所述的聚环糊精基儿茶素类纳米递送系统在制备治疗变应性鼻炎的药物中的应用。
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