CN110840826A - 一种鼻阻隔剂及其制备方法 - Google Patents
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Abstract
本发明公开了一种鼻阻隔剂及其制备方法。鼻阻隔剂由包含以下重量的原料制成:壳聚糖、甘油、包覆有保湿成分的脂质体、抗过敏剂、卡波姆、季铵盐防腐剂、余量为纯化水;其使用方便、舒适、安全、能有效阻隔过敏原在鼻黏膜的沉积、能治疗变应性鼻炎和干燥性鼻炎以及对变应性鼻炎及其合并的哮喘有预防作用的优点;其制备方法为:先将包覆有保湿成分的脂质体与有机酸混合,搅拌均匀,再加入壳聚糖;再加入卡波姆,搅拌均匀,得到混合物,备用;将甘油、季铵盐防腐剂和抗过敏剂加入纯化水中,搅拌均匀,得到溶液Ⅱ;将混合物加入溶液Ⅱ内,搅拌至凝胶状,静置,即可制得。本发明的制备方法具有工艺安全、易于生成凝胶的优点。
Description
技术领域
本发明涉及鼻阻隔剂技术领域,更具体地说,它涉及一种鼻阻隔剂及其制备方法。
背景技术
过敏性鼻炎即变应性鼻炎,是指特应性个体接触变应原后,主要由IgE介导的介质(主要是组胺)释放,并有多种免疫活性细胞和细胞因子等参与的鼻黏膜非感染性炎性疾病。引起过敏性鼻炎的原因:螨、花粉、动物的皮屑、真菌变应原、蟑螂变应原以及食物变应原等。过敏性鼻炎的常见症状:喷嚏、清水样涕、鼻塞、鼻痒等症状及伴有的眼痒、结膜充血等眼部症状;常见的体征:鼻黏膜苍白、水肿或鼻腔有水样分泌物等。
过敏性哮喘(哮喘)是由多种细胞特别是肥大细胞、嗜酸性粒细胞和T淋巴细胞参与的慢性气道炎症,在易感者中此种炎症可引起反复发作的喘息、气促、胸闷和(或)咳嗽等症状。过敏性哮喘常见发病原因:吸入物质为特异性和非特异性两种,前者如螨、花粉、真菌变应原或动物毛屑等。
过敏性鼻炎、过敏性哮喘是指同时发生的临床或亚临床的上呼吸道过敏(过敏性鼻炎)和下呼吸道过敏(哮喘)的症状,两者往往同时并存;临床症状的主要表现为鼻痒、喷嚏频频、流清鼻涕、鼻塞、咳嗽或喘息等症状,某些患者往往还伴有过敏性结膜炎的症状如眼痒、流泪等。
干燥性鼻炎一般认为长期受外界的物理或化学物质的刺激所致,如长期粉尘的机械性刺激,空气过热、过干的影响等。临床表现:鼻内发干,鼻腔分泌物减少,鼻内有刺痒感或异物感,经常引起喷嚏,灼热感,常诱使患者挖鼻或引起小量鼻出血等。
目前对于过敏原引起变应性鼻炎和合并哮喘一般采用盐水冲洗的方法,原理是通过冲洗掉过敏原(变应原)以期达到治疗目的,但是过敏原(变应原)已经与鼻黏膜接触并已经起作用,冲洗只是对症状的暂时缓解。对于干燥性鼻炎一般采用补水的方法来缓解干燥,但是滞留时间短或造成“流涕”感。鼻用及口服抗组胺药是缓解症状的有效手段,但所有的药品均有提示:不可以连续长时间使用,原因是连续长时间使用会带来药物性鼻炎、萎缩性鼻炎的风险。
总之,现有技术缺乏一种使用方便且有效的鼻阻隔剂,来应对上述鼻炎的症状。
发明内容
针对现有技术存在的不足,本发明的目的一在于提供一种鼻阻隔剂,其具使用方便、舒适、安全、能有效阻隔过敏原在鼻黏膜的沉积、从而可以改善、治疗变应性鼻炎和干燥性鼻炎以及对变应性鼻炎及其合并的哮喘有预防作用的优点。
本发明的第二个目的在于提供一种鼻阻隔剂的制备方法,其具有制备工艺安全、易于实施、易于生成凝胶且生产过程中不会产生危害环境或操作人员身体健康的物质的优点。
为实现上述第一个目的,本发明提供了如下技术方案:
一种鼻阻隔剂,所述鼻阻隔剂由包含以下重量的原料制成:
壳聚糖0.1%~0.4%、甘油2%~7%、包覆有保湿成分的脂质体0.5%~1.5%、抗过敏剂0.5%~1.7%、卡波姆0.05%~0.3%、季铵盐防腐剂0.05~0.2%、余量为纯化水。
通过采用上述技术方案,本发明中,各成分相互配合、相互作用,可制得一种新的凝胶型鼻阻隔剂,使用时将鼻阻隔剂直接涂布于鼻腔内,此时,鼻阻隔剂将过敏原(PM2.5及空气中其它常见的过敏源如花粉、尘螨、真菌、和动植物皮屑等颗粒物)与鼻黏膜隔开,阻止过敏原与鼻黏膜直接接触,从而有效缓解局部的过敏反应强度、也能在一定程度上预防变应性鼻炎及其合并的哮喘发作,且吸入性的过敏原能够粘附在涂布于鼻腔内的鼻阻隔剂上,然后随着鼻腔内的分泌物一起排出。鼻阻隔剂涂布于鼻腔内后,亲肤、舒适、可缓解干燥;不会造成“流涕”感,干净卫生;连续长时间使用不会带来药物性鼻炎、萎缩性鼻炎的风险,安全可靠。
脂质体是由磷脂分散在水中形成的封闭囊泡结构,是优良的药物运输载体,可用于包埋亲水性和疏水性活性成分,具有靶向、缓释、降低毒性和提高药物稳定性等作用,也具有一定的保湿性能,本发明中包敷有保湿成分的脂质体具有更优良的皮肤保湿性能,可缓解干燥,提高凝胶使用的舒适度。壳聚糖也称脱乙酰甲壳素,可以由广泛存在于自然界的几丁质经过脱乙酰制备而成,化学成分为聚葡萄糖胺(1-4)-2-氨基-B-D葡萄糖,壳聚糖是自然界的碱性多糖、无毒、具有生物粘附性、吸收促进和生物可降解性。在酸性条件下,用壳聚糖与包覆有保湿成分的脂质体混合,此时,阳离子型的壳聚糖与阴离子型的包覆有保湿成分的脂质体发生电荷作用,壳聚糖未完全脱乙酰化的酰基插入包覆有保湿成分的脂质体的脂膜中,使得壳聚糖分子镶嵌在包覆有保湿成分的脂质体表面,形成壳聚糖脂质体复合物,增加了保湿成分脂质体的稳定性和药物靶向性。
进一步地,所述卡波姆选自药用级卡波姆940、卡波姆941、卡波姆980或卡波姆971中的任意一种。
通过采用上述技术方案,卡波姆是聚烷基蔗糖或聚烷基季戊四醇与丙烯酸交联聚合物的共聚物,根据聚合时使用的材料不同和聚合度不同,形成了不同规格的产品。本发明中,卡波姆作为一种化学性质稳定、对皮肤黏膜无刺激的药用辅料,可以选择药用级卡波姆940、卡波姆941、卡波姆980或卡波姆971中的任意一种,再进一步的,优先选择药用级卡波姆940。以药用级卡波姆940为材料制得的凝胶基质为性能优异的水溶性基质,释药迅速,无油腻性,易于涂布,稳定性好,且具有一定的增稠作用,便于形成凝胶。
进一步地,所述抗过敏剂选自甘草酸二钾、马齿觅提取物和枇杷叶提取物中的至少一种。
通过采用上述技术方案,甘草酸二钾具有抗炎、抗过敏和促进上皮细胞组织再生等作用;甘草酸二钾与甘油等相互作用,还具有一定的保湿功效,能缓减皮肤干燥。本发明中,马齿觅提取物的主要成分为具有生物活性的生物碱和黄酮类物质,且所述生物碱含量至少为0.008%,黄酮类物质的含量至少为6.8%;马齿觅提取物可以与水以任意比例互溶,具有一定的抗菌、止痒功能,对疼痛和红肿有明显的抑制能力,且具有一定的保湿性能。枇杷叶提取物由枇杷叶经水提或醇提制成,主要成分为熊果酸,所述熊果酸的含量至少为30%;枇杷叶提取物具有镇静、抗炎、抗菌的功效。甘草酸二钾与马齿觅提取物中的生物碱等成分协同作用,产品能达到显著的抑菌和抗过敏效果,能降低肌肤的敏感度,还能有效锁水、补水,保持凝胶的水润性,使用舒适。
进一步地,所述鼻阻隔剂还包括平喘剂,所述平喘剂的重量占原料总重量的0.1%~0.3%。
通过采用上述技术方案,鼻阻隔剂的原料组分中包括平喘剂,可在一定程度上预防或减轻过敏原引起的变应性鼻炎和合并哮喘的症状,能在一定程度上止喘,顺气,缓解干燥。
进一步地,所述平喘剂选自苏子提取物和半夏提取物中的至少一种。
通过采用上述技术方案,苏子提取物选自紫苏子提取物或白苏子提取物中的任意一种,紫苏子提取物为紫苏子成熟果实经石油醚提取后得到的有效成分脂肪油,且所述脂肪油中亚麻油的含量大约为60%;紫苏子提取物具有止咳、平喘的作用,还具有一定的抗过敏功效。白苏子提取物为白苏子果实压榨的脂肪油,所述脂肪油中白苏子油的含量为50%~70%;其具有咳逆、平喘的作用。半夏提取物为新鲜采集的半夏块茎经有机溶剂提取后得到的有效成分总酸,所述总酸提取物中总游离有机酸(以琥珀酸计)的含量大约为38%;半夏提取物具有镇咳、止喘、顺气的作用。本发明中,优先选择紫苏子提取物,紫苏子提取物与抗过敏剂相互配合,能提高抗过敏剂的抗过敏性能和杀菌性能,且紫苏子提取物具有一定的防腐作用,能在一定程度上延长鼻阻隔剂的保质期。
进一步地,所述包覆有保湿成分的脂质体中的保湿成分选自透明质酸、聚葡糖苷、甘油、凡士林、单硬脂酸甘油酯、液体石蜡和十六醇中的至少一种。
通过采用上述技术方案,透明质酸、聚葡糖苷、甘油、凡士林、单硬脂酸甘油酯、液体石蜡和十六醇均为良好的保湿剂,可吸附并保留水分,维持鼻阻隔剂凝胶的水润性,提高鼻阻隔剂的润肤效果,给皮肤补充水分,从而维持皮肤水合作用,且同时能维护皮肤的屏障功能,有利于改善鼻阻隔剂的使用效果。
进一步地,所述季铵盐防腐剂选自聚季铵盐-1或十二烷基三甲基氯化铵中的任意一种。
通过采用上述技术方案,聚季铵盐-1(简称PQ-1)是由四甲基-2-丁烯-1,4-二胺和1,4-二氯-2-丁烯在一定条件下聚合反应,终端以三-β-羟乙基胺覆盖合成的一种新型的聚季铵盐抗菌剂,属于强阳离子化合物,完全溶于水,无刺激性,能防止鼻阻隔剂在一定时间内腐败变质,且有较好的杀菌性能。十二烷基三甲基氯化铵,为淡黄色透明胶体,可溶于水和乙醇,化学稳定性好,能防止鼻阻隔剂在一定时间内腐败变质,且与本发明中的其它组分有良好的配伍性,并且能发挥一定的乳化性能和杀菌性能。
为实现上述第二个目的,本发明提供了如下技术方案:
一种鼻阻隔剂的制备方法包括如下步骤:
⑴、将含保湿成分的脂质体与有机酸混合,搅拌均匀,将pH值控制在4~6,得到溶液Ⅰ;⑵、将壳聚糖加入溶液Ⅰ内,搅拌均匀,得到悬浮液;
⑶、将卡波姆加入悬浮液中,搅拌均匀,得到混合物,备用;
⑷、将甘油、季铵盐防腐剂和抗过敏剂加入纯化水中,搅拌均匀,得到溶液Ⅱ;
⑸、将备用的混合物加入溶液Ⅱ内,搅拌至凝胶状,静置,即可制得鼻阻隔剂。
通过采用上述技术方案,先将包覆有保湿成分的脂质体与有机酸混合,调节pH在4~6,然后再与壳聚糖混合,此时,有机酸为壳聚糖和包覆有保湿成分的脂质体提供酸性环境,壳聚糖分子镶嵌在包覆有保湿成分的脂质体表面,形成壳聚糖脂质体复合物,有利于壳聚糖的分散;之后,加入本身具有凝胶基质的卡波姆,其可与另一个具有凝胶基质的壳聚糖相互配合,具有增稠的效果,从而有利于凝胶成型,与此同时卡波姆可以作为悬浮液的稳定剂,便于悬浮液的稳定;将甘油、季铵盐防腐剂和抗过敏剂先加入纯化水中,有利于季铵盐防腐剂和抗过敏剂的均匀分散,后续当步骤⑶中备用的混合物加入到步骤⑷中的溶液Ⅱ内,搅拌均匀,即可制得凝胶型鼻阻隔剂。鼻阻隔剂的制备工艺安全,易于实施,易于生成凝胶且凝胶成型效果较好,成型的凝胶比较稳定,生产过程中不会产生危害环境或操作人员身体健康的物质,有利于保护环境。
进一步地,所述有机酸选自乙酸、草酸、苹果酸、琥珀酸或酒石酸中的任意一种。
通过采用上述技术方案,有机酸为壳聚糖和包覆有保湿成分的脂质体提供了一个酸性环境,便于壳聚糖的分散。本发明中,有机酸优先选择乙酸,乙酸为壳聚糖和包覆有保湿成分的脂质体提供酸性环境,有利于壳聚糖的分散,且有助于凝胶的形成。草酸,即乙二酸,无色透明结晶或粉末;苹果酸,又名2-羟基丁二酸,白色结晶体或结晶状粉末;琥珀酸学名为丁二酸,无色结晶,能溶于水和甘油;酒石酸即2,3-二羟基丁二酸。本发明中,用乙酸、草酸、苹果酸、琥珀酸或酒石酸均可以为壳聚糖和包覆有保湿成分的脂质体提供一个适宜的酸性环境。
进一步地,所述步骤⑵中,得到的悬浮液静置3h~6h后,再实施步骤⑶。
通过采用上述技术方案,将得到的悬浮液静置3h~6h,可以消除悬浮液中的泡泡,采用静置的物理消泡手段,在消除悬浮液内的泡泡的同时不会影响悬浮液的性能,便于凝胶的成型和性能的稳定。
综上所述,本发明具有以下有益效果:
第一、各成分相互配合、相互作用,可制得一种新的凝胶型的鼻阻隔剂,
该鼻阻隔剂能有效阻隔过敏原在鼻黏膜的沉积,从而可以改善、治疗变应性鼻炎和干燥性鼻炎,能预防或减轻变应性鼻炎及其合并的哮喘发作;
第二、使用时将鼻阻隔剂直接涂布于鼻腔内即可,使用方法简单方便,涂布后亲肤、可缓解干燥、不会造成“流涕”感、使用舒适,连续长时间使用不会带来药物性鼻炎、萎缩性鼻炎的风险,安全可靠;
第三、鼻阻隔剂的制备工艺安全,易于实施,易于生成凝胶且凝胶成型效果较好。
具体实施方式
以下结合实施例对本发明作进一步详细说明。
实施例
实施例1
一种鼻阻隔剂的制备方法包括如下步骤:
⑴、将0.5kg含保湿成分的脂质体与1L乙酸混合,搅拌均匀,此时,pH值为6,得到溶液Ⅰ;
⑵、将0.4kg壳聚糖加入溶液Ⅰ内,搅拌均匀,得到悬浮液;
⑶、将0.05kg药用级卡波姆940加入悬浮液中,搅拌均匀,得到混合物,备用;
⑷、将7kg甘油、0.1kg十二烷基三甲基氯化铵和0.5kg甘草酸二钾加入90.45L纯化水中,搅拌均匀,得到溶液Ⅱ;
⑸、将备用的混合物加入溶液Ⅱ内,搅拌至凝胶状,静置,即可制得鼻阻隔剂。
实施例2
实施例2与实施例1的区别在于,实施例2中含保湿成分的脂质体为1.5kg,壳聚糖为0.1kg,纯化水为89.75L,其它均与实施例1保持一致。
实施例3
实施例3与实施例1的区别在于,实施例3中含保湿成分的脂质体为1kg,壳聚糖为0.3kg,纯化水为90.05L,其它均与实施例1保持一致。
实施例4
实施例4与实施例3的区别在于,实施例4中药用级卡波姆940为0.1kg,纯化水为90L,其它均与实施例3保持一致。
实施例5
实施例5与实施例3的区别在于,实施例5中,药用级卡波姆940为0.3kg,纯化水为89.2L,其它均与实施例3保持一致。
实施例6
实施例6与实施例4的区别在于,实施例6中,用药用级卡波姆941代替药用级卡波姆940,其它均与实施例4保持一致。
实施例7
实施例7与实施例4的区别在于,实施例7中,用药用级卡波姆980代替药用级卡波姆940,其它均与实施例4保持一致。
实施例8
实施例8与实施例4的区别在于,实施例8中,用药用级卡波姆971代替药用级卡波姆940,其它均与实施例4保持一致。
实施例9
实施例9与实施例4的区别在于,实施例9中,甘草酸二钾为1.7kg,纯化水为88.8L,其它均与实施例4保持一致。
实施例10
实施例10与实施例4的区别在于,实施例10中,甘草酸二钾为0.8kg,纯化水为89.7L,其它均与实施例4保持一致。
实施例11
实施例11与实施例10的区别在于,实施例11中,用马齿觅提取物代替甘草酸二钾,其它均与实施例10保持一致。
实施例12
实施例12与实施例10的区别在于,实施例12中,用枇杷叶提取物代替甘草酸二钾,其它均与实施例10保持一致。
实施例13
实施例13与实施例10的区别在于,实施例13中,用0.3kg马齿觅提取和0.4kg甘草酸二钾代替0.8kg甘草酸二钾,纯化水为89.8L,其它均与实施例10保持一致。
实施例14
实施例14与实施例10的区别在于,实施例14中,用0.4kg马齿觅提取和0.4kg枇杷叶提取物替换甘草酸二钾,其它均与实施例10保持一致。
实施例15
一种鼻阻隔剂的制备方法包括如下步骤:
⑴、将1kg含保湿成分的脂质体与1L乙酸混合,搅拌均匀,此时,pH值为6,得到溶液Ⅰ;⑵、将0.3kg壳聚糖加入溶液Ⅰ内,搅拌均匀,得到悬浮液;
⑶、将0.1kg药用级卡波姆940加入悬浮液中,搅拌均匀,得到混合物,备用;
⑷、将7kg甘油、0.1kg十二烷基三甲基氯化铵、0.8kg甘草酸二钾和0.2kg紫苏子提取物、加入89.5L纯化水中,搅拌均匀,得到溶液Ⅱ;
⑸、将备用的混合物加入溶液Ⅱ内,搅拌至凝胶状,静置,即可制得鼻阻隔剂。
实施例16
实施例16与实施例15的区别在于,实施例16中,紫苏子提取物为0.1kg,纯化水为89.6L,其它均与实施例10保持一致。
实施例17
实施例17与实施例15的区别在于,实施例17中,用0.3半夏提取物代替0.2kg紫苏子提取物,纯化水为89.4L,其它均与实施例10保持一致。
实施例18
一种鼻阻隔剂的制备方法包括如下步骤:
⑴、将1kg含保湿成分的脂质体与1L乙酸混合,搅拌均匀,此时,pH值为6,得到溶液Ⅰ;⑵、将0.3kg壳聚糖加入溶液Ⅰ内,搅拌均匀,得到悬浮液,将悬浮液静置4h;
⑶、将0.1kg药用级卡波姆940加入静置后的悬浮液中,搅拌均匀,得到混合物,备用;
⑷、将7kg甘油、0.1kg十二烷基三甲基氯化铵、0.8kg甘草酸二钾和0.2kg紫苏子提取物、加入89.5L纯化水中,搅拌均匀,得到溶液Ⅱ;
⑸、将备用的混合物加入溶液Ⅱ内,搅拌至凝胶状,静置,即可制得鼻阻隔剂。
实施例19
实施例19与实施例18的区别在于,实施例19中,静置3小时,其它均与实施例18保持一致。
实施例20
实施例20与实施例18的区别在于,实施例20中,静置6小时,其它均与实施例18保持一致。
实施例21
一种鼻阻隔剂的制备方法包括如下步骤:
⑴、将1kg含保湿成分的脂质体与1L乙酸混合,搅拌均匀,此时,pH值为6,得到溶液Ⅰ;
⑵、将0.3kg壳聚糖加入溶液Ⅰ内,搅拌均匀,得到悬浮液,将悬浮液静置4h;
⑶、将0.1kg药用级卡波姆940加入静置后的悬浮液中,搅拌均匀,得到混合物,备用;
⑷、将2kg甘油、0.05kg聚季铵盐-1和0.8kg甘草酸二钾加入94.75L纯化水中,搅拌均匀,得到溶液Ⅱ;
⑸、将备用的混合物加入溶液Ⅱ内,搅拌至凝胶状,静置,即可制得鼻阻隔剂。
实施例22
一种鼻阻隔剂的制备方法包括如下步骤:
⑴、将1kg含保湿成分的脂质体与0.5L草酸混合,搅拌均匀,此时,pH值为5.5,得到溶液Ⅰ;
⑵、将0.3kg壳聚糖加入溶液Ⅰ内,搅拌均匀,得到悬浮液;
⑶、将0.1kg药用级卡波姆940加入静置后的悬浮液中,搅拌均匀,得到混合物,备用;
⑷、将2kg甘油、0.2kg聚季铵盐-1、0.8kg甘草酸二钾和0.2kg白苏子提取物加入94.9L纯化水中,搅拌均匀,得到溶液Ⅱ;
⑸、将备用的混合物加入溶液Ⅱ内,搅拌至凝胶状,静置,即可制得鼻阻隔剂。
对比例对比例1
对比例1与实施18的区别在于,对比例1中没有加入药用级卡波姆940,其它均与实施例18保持一致。
对比例2
对比例2与实施18的区别在于,对比例2中用脂质体代替包覆有保湿成分的脂质体,其它均与实施例18保持一致。
对比例3
对比例3与实施18的区别在于,对比例3中没有加入抗过敏剂,其它均与实施例18保持一致。
性能检测试验
1、检测各实施例制得的各鼻阻隔剂样品的基本性能
1)、观察实施例1~22和对比例1~3所制得的鼻阻隔剂的外观,可见,鼻阻隔剂产品为无色或白色凝胶剂,色泽均匀,无异物,且无味,无臭;
2)、按《中华人民共和国药典》2015版pH值测定方法和旋转式黏度计方法分别检测实施例1~22和对比例1~3所制得的鼻阻隔的pH值和粘度,检测结果如表1所示;按标准检测实施例1~22和对比例1~3所制得的鼻阻隔剂的重金属总量(以Pb计)和氢氧化钠含量,检测结果如表1所示;
3)、按GB 15979-2002《一次性使用卫生用品卫生标准》附录中微生物限度试验方法检测实施例1~22和对比例1~3所制得的鼻阻隔的细菌菌落总数、真菌菌落总数、大肠杆菌、绿脓杆菌、金黄色葡萄球菌及溶血性链球菌,检测结果如表2所示;
表1基本性能检测表
从表1可以看出,除了对比例1的粘度不符合标准范围外,其余实施例1~22和对比例1~3的各项检测均在标准范围内,由此可见,用本发明的配方和工艺制备的凝胶型鼻阻隔剂符合基本性能的检测标准,安全可靠,可放心使用;观察实施例1~8的粘度数据可知,壳聚糖、包覆有保湿成分的脂质体与卡波姆三者的用量比例以及卡波姆的种类、用量等均影响凝胶的成型,由对比例1与其余的粘度数据可知,具有凝胶基质的卡波姆与壳聚糖相互作用,有利于凝胶的成型和稳定。
表2卫生标准检测表
从表2可以看出,实施例1~22和对比例1~3的各项检测均在标准范围内,由此可见,用本发明的配方和工艺制备的凝胶型鼻阻隔剂符合基本性能的检测标准,安全可靠,可放心使用;由实施例4、9~14和对比例3的数据可知,抗过敏剂在一定程度上可杀菌、消毒,可提高鼻阻隔剂的安全性。
2、效果检验
研究对象为2018年7月~2019年3月就诊于吉林大学中日联谊医院耳鼻咽喉头颈外科门诊明确诊段变应性鼻炎的患者,入试者严格除外非变应性鼻炎,慢性鼻鼻窦炎伴或不伴鼻息肉患者,病程均超过一年。其中,男34例,女45例;年龄8~32岁,其中,小于18岁的儿童病例为48人。所有入试者共78人,随机分配为26个小组,每个小组对应使用一个实施例或对比例制得的鼻阻隔剂。
入组前均通过鼻内镜检查,过敏原检查,将鼻阻隔剂凝胶用喷出装置(喷出装置可以将凝胶颗粒调节壳聚糖粒径控制在100和900nm之间,这种分散颗粒可以更好的覆盖鼻黏膜组织,形成保护变应原附着的凝胶层)每日给予患者鼻喷两次,每次0.125毫升;鼻喷盐水对照组每天给予0.9%氯化钠溶液鼻喷两次,每次0.125毫升。所有对象在治疗前,治疗后一周及一个月均进行视觉模拟量表(visual analog scale,VAS)和症状评分(symptomrating score,SRS)的评估。
症状评分的方法如下:0分,正常无不适;1分,轻度,(症状轻微);2分,中度(症状明显,但尚能忍受);3分,重度(症状难以忍受,影响正常生活)。取3个症状的视觉模拟量表(VAS)的平均值计为最终VAS值,症状评分以3个症状的评分之和作为最终结果,部分小于十岁的较小病人的VAS和症状评分由家长代为完成。
表3试验效果记录表
从表3可以看出,观察上述实施例1~22、对比例1~3和鼻喷盐水试验组的试验数据可知,实施例1~22的试验效果最好,其次是对比例1~3的试验效果,鼻喷盐水组的试验效果最差,由此可以得出,根据本发明的配方和工艺制备的鼻阻隔剂能有效阻隔过敏原在鼻黏膜的沉积,从而可以改善、治疗变应性鼻炎和干燥性鼻炎,能预防或减轻变应性鼻炎及其合并的哮喘发作;由对比例1~3与实施例1~22的试验数据可知,本发明中,鼻阻隔剂中的各成分相互协助,共同配合,影响鼻阻隔剂的效果,特别是卡波姆、抗过敏剂和含保湿成分的脂质体等,对鼻阻隔剂的效果影响较大。
本具体实施例仅仅是对本发明的解释,其并不是对本发明的限制,本领域技术人员在阅读完本说明书后可以根据需要对本实施例做出没有创造性贡献的修改,但只要在本发明的权利要求范围内都受到专利法的保护。
Claims (10)
1.一种鼻阻隔剂,其特征在于,所述鼻阻隔剂由包含以下重量的原料制成:
壳聚糖0.1%~0.4%、甘油2%~7%、包覆有保湿成分的脂质体0.5%~1.5%、抗过敏剂0.5%~1.7%、卡波姆0.05%~0.3%、季铵盐防腐剂0.05~0.2%、余量为纯化水。
2.根据权利要求1所述的一种鼻阻隔剂,其特征在于,所述卡波姆选自药用级卡波姆940、卡波姆941、卡波姆980或卡波姆971中的任意一种。
3.根据权利要求1所述的一种鼻阻隔剂,其特征在于,所述抗过敏剂选自甘草酸二钾、马齿觅提取物和枇杷叶提取物中的至少一种。
4.根据权利要求1或3所述的一种鼻阻隔剂,其特征在于,所述鼻阻隔剂还包括平喘剂,所述平喘剂的重量占原料总重量的0.1%~0.3%。
5.根据权利要求1所述的一种鼻阻隔剂,其特征在于,所述平喘剂选自苏子提取物和半夏提取物中的至少一种。
6.根据权利要求1所述的一种鼻阻隔剂,其特征在于,所述包覆有保湿成分的脂质体中的保湿成分选自透明质酸、聚葡糖苷、甘油、凡士林、单硬脂酸甘油酯、液体石蜡和十六醇中的至少一种。
7.根据权利要求1所述的一种鼻阻隔剂,其特征在于,所述季铵盐防腐剂选自聚季铵盐-1或十二烷基三甲基氯化铵中的任意一种。
8.根据权利要求1~7任一项所述鼻阻隔剂的制备方法,其特征在于,所述制备方法包括如下步骤:
⑴、将包覆有保湿成分的脂质体与有机酸混合,搅拌均匀,将pH值控制在4~6,得到溶液Ⅰ;
⑵、将壳聚糖加入溶液Ⅰ内,搅拌均匀,得到悬浮液;
⑶、将卡波姆加入悬浮液中,搅拌均匀,得到混合物,备用;
⑷、将甘油、季铵盐防腐剂和抗过敏剂加入纯化水中,搅拌均匀,得到溶液Ⅱ;
⑸、将备用的混合物加入溶液Ⅱ内,搅拌至凝胶状,静置,即可制得鼻阻隔剂。
9.根据权利要求8所述鼻阻隔剂的制备方法,其特征在于,所述有机酸选自乙酸、草酸、苹果酸、琥珀酸或酒石酸中的任意一种。
10.根据权利要求8所述鼻阻隔剂的制备方法,其特征在于,所述步骤⑵中,得到的悬浮液静置3h~6h后,再实施步骤⑶。
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