CN110200915A - 一种富马酸卢帕他定乳剂型鼻腔喷雾剂及其制备方法 - Google Patents
一种富马酸卢帕他定乳剂型鼻腔喷雾剂及其制备方法 Download PDFInfo
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- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
- A61K31/4545—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
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Abstract
本发明涉及生物医药技术领域，尤其涉及一种富马酸卢帕他定乳剂型鼻腔喷雾剂及其制备方法，所述滴鼻剂处方含有如下药用级组分：富马酸卢帕他定2‑5%、油相5‑25%、乳化剂10‑20%、水相40‑65%、渗透压调节剂0.5‑5%、抑菌剂0.05‑0.1%，pH调节剂0.5‑5%。采用高速剪切乳匀机乳化制备滴鼻液，无菌操作，分装于特殊喷雾装置。
Description
技术领域
本发明属于医药技术领域，涉及一种药物喷雾剂及其制备方法，具体是指一种富马酸卢帕他定乳剂型鼻腔喷雾剂及其制备方法。
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。近几年，过敏性闭眼的发作趋势呈上升之势。组胺是在***反应早中期以及过敏症状出现时由IgE介导释放地炎症介质；血小板活化因子则是前呼吸道炎症中另一重要的炎症介质。抑制组胺、血小板活化因子等炎症介质活性是治疗炎症的主要措施。
卢帕他定是目前上市的唯一既有抗组胺作用又拮抗血小板活化因子活性的抗过敏药，可治疗季节性和常年性过敏性鼻炎。其对H1受体结合能力相较于特非那定、氯雷他定、西替利嗪等强。富马酸卢帕他定为无臭，无味，在乙醇中微溶，水中不溶。
富马酸卢帕他定现有剂型是片剂胶囊剂，通过口服防治过敏性鼻炎。服用之后通过胃肠道吸收入血，再随血液分布到靶部位起治疗作用，起效慢；服药后容易出现嗜睡、头痛、疲乏等不良反应。本发明拟将富马酸卢帕他定制成乳剂型鼻腔喷雾剂，具有如下优点：①通过局部定位喷雾快速缓解过敏性鼻炎症状；②少量喷雾后药物直达鼻腔病灶，减少用药剂量，从而在一定程度上可减轻不良反应；③鼻腔粘膜毛细血管丰富，利于药物吸收，且可避免肝脏的首过效应，药物的生物利用度提高；④使用方便，且能起到清洗鼻腔的作用；⑤乳剂型鼻腔喷雾剂含有适量表面活性剂，能增加药物跨生物屏障性能，促进药物跨膜吸收。
发明内容
针对现有富马酸卢帕他定片剂、胶囊剂在治疗过敏性鼻炎时起效慢、用药剂量大、不良反应明显的不足，本发明旨在提供一种起效快、剂量小、不良反应小，使用方便、且能清洗鼻腔的富马酸卢帕他定乳剂型滴鼻剂及其制备方法。
为了实现上述目的，本发明采用如下技术方案：
一种富马酸卢帕他定乳剂型鼻腔喷雾剂，其特征在于，由富马酸卢帕他定、油相、乳化剂、水相、渗透压调节剂和pH调节剂组成，各组分的质量比为：
富马酸卢帕他定2-5％、油相5-25％、乳化剂10-20％、水相40-65％、渗透压调节剂0.5-5％、抑菌剂0.05-0.1％，pH调节剂0.5-5％。
作为优选，所述油相为蓖麻油、中链甘油酸三脂、油酸乙酯、薄荷油中的一种或几种；所述水相为注射用水。
作为优选，所述乳化剂为聚氧乙烯40氢化蓖麻油、聚山梨酯20、泊洛沙姆188中的一种或两种。
作为优选，所述渗透压调节剂为丙二醇、氯化钠、葡萄糖、甘露醇中的一种或几种。
作为优选，所述抑菌剂为尼泊金酯类、苯甲酸钠或三氯叔丁醇。
作为优选，所述pH调节剂为柠檬酸。
一种富马酸卢帕他定乳剂型鼻腔喷雾剂的制备方法，包括如下步骤：
(1)油相的制备：准确称取处方量富马酸卢帕他定和油相，涡旋均匀，60℃水浴中预热；
(2)水相的制备：准确称取处方量的渗透压调节剂、抑菌剂和乳化剂于注射用水中，60℃水浴中预热、溶解；
(3)制备初乳：将步骤(1)所得油相加入步骤(2)所得水相，用高速剪切乳匀机乳化2-5min，5000-10000rpm；
(4)调节pH值：用pH调节剂调整pH至5.5-6.5，加注射用水至处方量，过滤；
(5)灭菌与分装：生产环境和设备尽量无菌，无菌操作；分装于特定喷雾装置。
本发明所具有的有益效果：
本发明的一种富马酸卢帕他定乳剂型鼻腔喷雾剂富马酸卢帕他定制成乳剂型鼻腔喷雾剂能减少用药剂量，提高药物生物利用度，降低药物不良反应，达到快速解除过敏性鼻炎的效果，同时又能清洗鼻腔的过敏原和污物，更好地发挥富马酸卢帕他定的抗过敏作用。
具体实施方式
下面结合具体实施例，进一步详细阐明本发明。实施例中未注明具体条件的实验方法，通常按照常规条件以及手册中所述的条件，或按照制造厂商所建议的条件；所用的通用设备、材料、试剂等，如无特殊说明，均可从商业途径得到。
实施例1
富马酸卢帕他定乳剂型滴鼻剂处方组成如表1。
表1.富马酸卢帕他定乳剂型滴鼻剂处方
富马酸卢帕他定乳剂型滴鼻剂制备方法：
(1)油相的制备：准确称取处方量富马酸卢帕他定、油酸乙酯/薄荷油(10:1，w/w)，涡旋均匀，60℃水浴中预热；
(2)水相的制备：准确称取处方量的氯化钠、尼泊金乙酯和聚山梨酯20于注射用水中，60℃水浴中预热、溶解；
(3)制备初乳：将步骤(1)所得油相加入步骤(2)所得水相，用高速剪切乳匀机乳化2-5min，5000-10000rpm；
(4)调节pH值：用柠檬酸水溶液调整pH至5.5-6.5，加注射用水至处方量，过滤；
(5)灭菌与分装：生产环境和设备尽量无菌，无菌操作；分装于特定喷雾装置。
实施例2
富马酸卢帕他定乳剂型滴鼻剂处方组成如表2。
表2.富马酸卢帕他定乳剂型滴鼻剂处方
富马酸卢帕他定乳剂型滴鼻剂制备方法：
(1)油相的制备：准确称取处方量富马酸卢帕他定和中链甘油酸三脂，涡旋均匀，60℃水浴中预热；
(2)水相的制备：准确称取处方量的氯化钠、苯甲酸钠和聚氧乙烯40氢化蓖麻油于注射用水中，60℃水浴中预热、溶解；
(3)制备初乳：将步骤(1)所得油相加入步骤(2)所得水相，用高速剪切乳匀机乳化2-5min，5000-10000rpm；
(4)调节pH值：用柠檬酸水溶液调整pH至5.5-6.5，加注射用水至处方量，过滤；
(5)灭菌与分装：生产环境和设备尽量无菌，无菌操作；分装于特定喷雾装置。
实施例3
富马酸卢帕他定乳剂型滴鼻剂处方组成如表3。
表3.富马酸卢帕他定乳剂型滴鼻剂处方
富马酸卢帕他定乳剂型滴鼻剂制备方法：
(1)油相的制备：准确称取处方量富马酸卢帕他定和蓖麻油，涡旋均匀，于60℃水浴中预热；
(2)水相的制备：准确称取处方量的氯化钠、尼泊金乙酯和泊洛沙姆188于注射用水中，60℃水浴中预热、溶解；
(3)制备初乳：将步骤(1)所得油相加入步骤(2)所得水相，用高速剪切乳匀机乳化2-5min，5000-10000rpm；
(4)调节pH值：用柠檬酸水溶液调整pH至5.5-6.5，加注射用水至处方量，过滤；
(5)灭菌与分装：生产环境和设备尽量无菌，无菌操作；分装于特定喷雾装置。
以上内容是结合具体的优选实施方式对本发明所作的进一步详细说明，不能认定本发明的具体实施只局限于这些说明。对于本发明所属技术领域的普通技术人员来说，在不脱离本发明构思的前提下，还可以做出若干简单推演或替换，都应当视为属于本发明的保护范围。
Claims (7)
1.一种富马酸卢帕他定乳剂型鼻腔喷雾剂，其特征在于，由富马酸卢帕他定、油相、乳化剂、水相、渗透压调节剂和pH调节剂组成，各组分的质量比为：
富马酸卢帕他定2-5%、油相5-25%、乳化剂10-20%、水相40-65%、渗透压调节剂0.5-5%、抑菌剂0.05-0.1%，pH调节剂0.5-5%。
2.按照权利要求1所述的富马酸卢帕他定乳剂型鼻腔喷雾剂，其特征在于，所述油相为蓖麻油、中链甘油酸三脂、油酸乙酯、薄荷油中的一种或几种；所述水相为注射用水。
3.按照权利要求1所述的富马酸卢帕他定乳剂型鼻腔喷雾剂，其特征在于，所述乳化剂为聚氧乙烯40氢化蓖麻油、聚山梨酯20、泊洛沙姆188中的一种或两种。
4.按照权利要求1所述的富马酸卢帕他定乳剂型鼻腔喷雾剂，其特征在于，所述渗透压调节剂为丙二醇、氯化钠、葡萄糖、甘露醇中的一种或几种。
5.按照权利要求1所述的富马酸卢帕他定乳剂型鼻腔喷雾剂，其特征在于，所述抑菌剂为尼泊金酯类、苯甲酸钠或三氯叔丁醇。
6.按照权利要求1所述的富马酸卢帕他定乳剂型鼻腔喷雾剂，其特征在于，所述pH调节剂为柠檬酸。
7.一种权利要求1-6所述的富马酸卢帕他定乳剂型鼻腔喷雾剂的制备方法，包括如下步骤：
（1）油相的制备：准确称取处方量富马酸卢帕他定和油相，涡旋均匀，60℃水浴中预热；
（2）水相的制备：准确称取处方量的渗透压调节剂、抑菌剂和乳化剂于注射用水中，60℃水浴中预热、溶解；
（3）制备初乳：将步骤（1）所得油相加入步骤（2）所得水相，用高速剪切乳匀机乳化2-5min，5000-10000 rpm；
（4）调节pH值：用pH调节剂调整pH至5.5-6.5，加注射用水至处方量，过滤；
（5）灭菌与分装：生产环境和设备尽量无菌，无菌操作；分装于特定喷雾装置。
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