CN114191417A - 一种用于宠物的雾化吸入剂 - Google Patents
一种用于宠物的雾化吸入剂 Download PDFInfo
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Abstract
本发明公开了一种用于宠物的雾化吸入剂,所述吸入剂主料包括以下份数的成分:酮咯酸氨丁三醇20‑30份,凝胶基质10‑15份,甲醇5‑10份,所述吸入剂辅料包括以下份数的成分:PH调节剂2‑5份,促进吸收剂5‑8份,保湿剂2‑5份,缓冲液5‑8份。本发明通过将酮咯酸氨丁三醇做为主料,酮咯酸氨丁三醇本身具备年良好的消炎镇痛作用,并在合成过程中,通过加入PH调节剂调节雾化吸入剂的PH值达到7.2,避免雾化吸入剂吸入时刺激宠物鼻黏膜,预防鼻腔内致病菌的生长,然后合成时依次加入促进吸收剂和磷酸二氢钾与氢氧化钠制备的缓冲液,不仅使得合成后的雾化吸入剂便于吸收,而且提高雾化吸入剂的稳定性。
Description
技术领域
本发明涉及雾化吸入剂,特别是涉及一种用于宠物的雾化吸入剂。
背景技术
对于患有上、下呼吸道疾病的宠物来说,雾化吸入剂是最高效的一种治疗方式,通过雾化器将将雾化吸入剂雾化,使其被宠物随着呼吸进入呼吸道以达到肺部,在吸入过程中药物不仅能是呼吸道表面消炎,还可以被身体吸收,使药效快速发生。
现有技术存在以下不足:现有雾化吸入剂吸入时会刺激宠物鼻黏膜,引起宠物的不适,并容易导致鼻腔内病菌的生长,且雾化吸入剂的稳定性差,不便于吸收。
发明内容
本发明提供一种用于宠物的雾化吸入剂,通过将酮咯酸氨丁三醇做为主料,酮咯酸氨丁三醇本身具备年良好的消炎镇痛作用,并在合成过程中,通过加入PH调节剂调节雾化吸入剂的PH值达到7.2,避免雾化吸入剂吸入时刺激宠物鼻黏膜,预防鼻腔内致病菌的生长,然后合成时依次加入促进吸收剂和磷酸二氢钾与氢氧化钠制备的缓冲液,不仅使得合成后的雾化吸入剂便于吸收,而且提高雾化吸入剂的稳定性,以解决背景技术中提出的问题。
为实现上述目的,本发明采用的技术方案如下:所述吸入剂主料包括以下份数的成分:酮咯酸氨丁三醇30份,凝胶基质15份,甲醇10份,所述吸入剂辅料包括以下份数的成分:PH调节剂5份,促进吸收剂8份,保湿剂5份,缓冲液8份;
优选的,凝胶基质优选为卡波姆934,促进吸收剂包括丙二醇、水溶性氮酮以及尿素,促进吸收剂由丙二醇、水溶性氮酮以及尿素中的一种或多种组成;
优选的,促进吸收剂优选为乙二胺四乙酸二钠;乙二胺四乙酸二钠为白色结晶性粉末,能溶于水,不溶于乙醇、乙醚,其水溶液的PH为5.3,可改变鼻黏膜结构,使鼻黏膜通透性増强,对药物的吸收有着明显的促进作用。
优选的,缓冲液由磷酸二氢钠和氢氧化钠组成,PH为6.8。
优选的,在确定雾化吸入剂的配方后,我们还需要制备雾化吸入剂,制备方法主要包括以下步骤:
1、纯化水置于烧杯中,先加入磷酸二氢钾,搅拌使其溶解后再加入氢氧化钠,搅拌至溶解,即得PH为11.59的缓冲液;
2、在缓冲液中依次加入的促进吸收剂、甲醇和酮咯酸氨丁三醇,超声溶解后使成浅黄色的澄清溶液剂,在澄清溶液剂中依次加入PH调节剂和保湿剂后,在40℃水浴锅中加热10min,加热过程中不断搅拌,冷却后得到PH值为7.2的雾化吸入剂。
与现有技术相比,本发明具有以下有益效果:
本发明通过将酮咯酸氨丁三醇做为主料,酮咯酸氨丁三醇本身具备年良好的消炎镇痛作用,并在合成过程中,通过加入PH调节剂调节雾化吸入剂的PH值达到7.2,避免雾化吸入剂吸入时刺激宠物鼻黏膜,预防鼻腔内致病菌的生长,然后合成时依次加入促进吸收剂和磷酸二氢钾与氢氧化钠制备的缓冲液,不仅使得合成后的雾化吸入剂便于吸收,而且提高雾化吸入剂的稳定性。
具体实施方式
下面结合实施例对本发明作进一步说明,本发明的方式包括但不仅限于以下实施例。
实施例1
本实施例提供一种用于宠物的雾化吸入剂,所述吸入剂主料包括以下份数的成分:酮咯酸氨丁三醇20份,凝胶基质10份,甲醇5份,所述吸入剂辅料包括以下份数的成分:PH调节剂2份,促进吸收剂5份,保湿剂2份,缓冲液5份;
其中,凝胶基质优选为卡波姆934,促进吸收剂包括丙二醇、水溶性氮酮以及尿素,促进吸收剂由丙二醇、水溶性氮酮以及尿素中的一种或多种组成。
合适的PH值可避免刺激鼻黏膜,是药物以非离子型的状态而被吸收,预防鼻腔内致病菌的生长,维持鼻黏膜纤毛的正常运动,溶菌酶是鼻内分泌物,与酸性PH环境下能杀灭细菌,而在碱性环境下则不起作用,导致鼻内组织易受细菌感染;
因此,鼻用制剂的PH应维持在5.5-7.5,且药物以非离子型状态存在,此时药物最容易被吸收,本实施例中的PH调节剂包括磷酸二氢钾和氢氧化钠,磷酸二氢钾和氢氧化钠在药剂中经常作为PH调节剂,可以使得药液的PH值和宠物鼻粘膜的PH相近,避免PH过高或过低对鼻粘膜造成刺激,
添加吸收促进剂可以增加雾化吸入剂的药物吸收作用,增加药物对鼻黏膜的穿透作用,从而提高药物的生物利用度,其作用机理主要有以下几个方面:
(1)降低黏液层黏度,提高黏膜通透性;
(2)与鼻黏膜上的糖蛋白结合,引起磷脂排列紊乱,改变膜结构,促进膜孔的形成,増加黏膜的流动性;
(3)改变鼻黏膜的电位和阻抗,使上皮细胞之间的紧密连接暂时疏松、断裂,增加细胞间的通透性;
(4)抑制鼻腔中蛋白水解酶的活性;
(5)减小黏液层的黏度,增加膜的渗透性;
(6)增加鼻血流速度,提高鼻黏膜两侧的药物浓度梯度;
(7)増加与鼻黏膜的黏附作用,延长鼻腔内滞留时间;
通常以上机制中的一种作用或几种作用协同促进了药物吸收,目前常用的鼻腔吸收促进剂主要包括:胆酸盐类(牛磺胆酸钠、脱氧胆酸钠等)、表面活性剂类(聚氧乙烯月桂醇醚、水杨酸盐等)、脂肪酸类(油酸、单油酸甘油酯等)、金属离子螯合物类(乙二胺四乙酸钠、水杨酸盐等)、甘草次酸及其衍生物类、磷脂类及衍生物(溶血卵磷脂)、氨基酸及其衍生物以及环糊精及其衍生物(乙二胺四乙酸二钠);
本实施例中,理想的吸收促进剂应对鼻黏膜无毒、无刺激性、无异臭、不致敏,对鼻黏膜的作用是可逆的,且作用强而持久、用量小,不同种类的吸收促进剂,促进吸收的效果不同,药物种类、药物相对分子质量与促进作用也有密切关系;
其中,环糊精及其衍生物因安全低毒在鼻黏膜给药领域得到广泛应用,环糊精的促进吸收机理与以下因素有关:
(1)包合提取细胞膜的脂溶性成分,使膜通透性增大;
(2)改变细胞间紧密蛋白的分布,打开细胞间屏障层,提高鼻黏膜通透性;
因此,本实施例中促进吸收剂优选为乙二胺四乙酸二钠;乙二胺四乙酸二钠为白色结晶性粉末,能溶于水,不溶于乙醇、乙醚,其水溶液的PH为5.3,可改变鼻黏膜结构,使鼻黏膜通透性増强,对药物的吸收有着明显的促进作用。
缓冲液由磷酸二氢钠和氢氧化钠组成,PH为6.8。
实施例2
本实施例提供一种用于宠物的雾化吸入剂,所述吸入剂主料包括以下份数的成分:酮咯酸氨丁三醇30份,凝胶基质15份,甲醇10份,所述吸入剂辅料包括以下份数的成分:PH调节剂5份,促进吸收剂8份,保湿剂5份,缓冲液8份;
其中,凝胶基质优选为卡波姆934,促进吸收剂包括丙二醇、水溶性氮酮以及尿素,促进吸收剂由丙二醇、水溶性氮酮以及尿素中的一种或多种组成。
合适的PH值可避免刺激鼻黏膜,是药物以非离子型的状态而被吸收,预防鼻腔内致病菌的生长,维持鼻黏膜纤毛的正常运动,溶菌酶是鼻内分泌物,与酸性PH环境下能杀灭细菌,而在碱性环境下则不起作用,导致鼻内组织易受细菌感染;
因此,鼻用制剂的PH应维持在5.5-7.5,且药物以非离子型状态存在,此时药物最容易被吸收,本实施例中的PH调节剂包括磷酸二氢钾和氢氧化钠,磷酸二氢钾和氢氧化钠在药剂中经常作为PH调节剂,可以使得药液的PH值和宠物鼻粘膜的PH相近,避免PH过高或过低对鼻粘膜造成刺激,
添加吸收促进剂可以增加雾化吸入剂的药物吸收作用,增加药物对鼻黏膜的穿透作用,从而提高药物的生物利用度,其作用机理主要有以下几个方面:
(1)降低黏液层黏度,提高黏膜通透性;
(2)与鼻黏膜上的糖蛋白结合,引起磷脂排列紊乱,改变膜结构,促进膜孔的形成,増加黏膜的流动性;
(3)改变鼻黏膜的电位和阻抗,使上皮细胞之间的紧密连接暂时疏松、断裂,增加细胞间的通透性;
(4)抑制鼻腔中蛋白水解酶的活性;
(5)减小黏液层的黏度,增加膜的渗透性;
(6)增加鼻血流速度,提高鼻黏膜两侧的药物浓度梯度;
(7)増加与鼻黏膜的黏附作用,延长鼻腔内滞留时间;
通常以上机制中的一种作用或几种作用协同促进了药物吸收,目前常用的鼻腔吸收促进剂主要包括:胆酸盐类(牛磺胆酸钠、脱氧胆酸钠等)、表面活性剂类(聚氧乙烯月桂醇醚、水杨酸盐等)、脂肪酸类(油酸、单油酸甘油酯等)、金属离子螯合物类(乙二胺四乙酸钠、水杨酸盐等)、甘草次酸及其衍生物类、磷脂类及衍生物(溶血卵磷脂)、氨基酸及其衍生物以及环糊精及其衍生物(乙二胺四乙酸二钠);
本实施例中,理想的吸收促进剂应对鼻黏膜无毒、无刺激性、无异臭、不致敏,对鼻黏膜的作用是可逆的,且作用强而持久、用量小,不同种类的吸收促进剂,促进吸收的效果不同,药物种类、药物相对分子质量与促进作用也有密切关系;
其中,环糊精及其衍生物因安全低毒在鼻黏膜给药领域得到广泛应用,环糊精的促进吸收机理与以下因素有关:
(1)包合提取细胞膜的脂溶性成分,使膜通透性增大;
(2)改变细胞间紧密蛋白的分布,打开细胞间屏障层,提高鼻黏膜通透性;
因此,本实施例中促进吸收剂优选为乙二胺四乙酸二钠;乙二胺四乙酸二钠为白色结晶性粉末,能溶于水,不溶于乙醇、乙醚,其水溶液的PH为5.3,可改变鼻黏膜结构,使鼻黏膜通透性増强,对药物的吸收有着明显的促进作用。
缓冲液由磷酸二氢钠和氢氧化钠组成,PH为6.8。
实施例3
进一步的,在确定雾化吸入剂的配方后,我们还需要制备雾化吸入剂,制备方法主要包括以下步骤:
1、纯化水置于烧杯中,先加入磷酸二氢钾,搅拌使其溶解后再加入氢氧化钠,搅拌至溶解,即得PH为11.59的缓冲液;
2、在缓冲液中依次加入的促进吸收剂、甲醇和酮咯酸氨丁三醇,超声溶解后使成浅黄色的澄清溶液剂,在澄清溶液剂中依次加入PH调节剂和保湿剂后,在40℃水浴锅中加热10min,加热过程中不断搅拌,冷却后得到PH值为7.2的雾化吸入剂;
该雾化吸入剂通过将酮咯酸氨丁三醇做为主料,酮咯酸氨丁三醇本身具备年良好的消炎镇痛作用,并在合成过程中,通过加入PH调节剂调节雾化吸入剂的PH值达到7.2,避免雾化吸入剂吸入时刺激宠物鼻黏膜,预防鼻腔内致病菌的生长,然后合成时依次加入促进吸收剂和磷酸二氢钾与氢氧化钠制备的缓冲液,不仅使得合成后的雾化吸入剂便于吸收,而且提高雾化吸入剂的稳定性。
上述实施例仅为本发明的优选实施方式之一,凡在本发明的主体设计思想和精神上作出的毫无实质意义的改动或润色,其所解决的技术问题仍然与本发明一致的,均应当包含在本发明的保护范围之内。
Claims (9)
1.一种用于宠物的雾化吸入剂,其特征在于,所述吸入剂主料包括以下份数的成分:酮咯酸氨丁三醇20-30份,凝胶基质10-15份,甲醇5-10份,所述吸入剂辅料包括以下份数的成分:PH调节剂2-5份,促进吸收剂5-8份,保湿剂2-5份,缓冲液5-8份。
2.根据权利要求1所述的一种用于宠物的雾化吸入剂,其特征在于,所述吸入剂主料包括以下份数的成分:酮咯酸氨丁三醇20份,凝胶基质10份,甲醇5份,所述吸入剂辅料包括以下份数的成分:PH调节剂2份,促进吸收剂5份,保湿剂2份,缓冲液5份。
3.根据权利要求1所述的一种用于宠物的雾化吸入剂,其特征在于,所述吸入剂主料包括以下份数的成分:酮咯酸氨丁三醇30份,凝胶基质15份,甲醇10份,所述吸入剂辅料包括以下份数的成分:PH调节剂5份,促进吸收剂8份,保湿剂5份,缓冲液8份。
4.根据权利要求3所述的一种用于宠物的雾化吸入剂,其特征在于,所述凝胶基质优选为卡波姆934。
5.根据权利要求4所述的一种用于宠物的雾化吸入剂,其特征在于,所述吸收促进剂包括乙二胺四乙酸二钠、牛磺胆酸钠、脱氧胆酸钠、聚氧乙烯月桂醇醚、水杨酸盐等、油酸以及单油酸甘油酯中的任意一种。
6.根据权利要求5所述的一种用于宠物的雾化吸入剂,其特征在于,所述所述缓冲液由磷酸二氢钠和氢氧化钠组成。
7.根据权利要求6所述的一种用于宠物的雾化吸入剂,其特征在于,所述促进吸收剂由丙二醇、水溶性氮酮以及尿素,促进吸收剂由丙二醇、水溶性氮酮以及尿素中的一种或多种组成。
8.一种如权利要求1-7任一项所述的一种用于宠物的雾化吸入剂的制备方法,其特征在于,所述制备方法包括以下步骤:
(1)纯化水置于烧杯中,先加入磷酸二氢钾,搅拌使其溶解后再加入氢氧化钠,搅拌至溶解,即得缓冲液;
(2)在缓冲液中依次加入的促进吸收剂、甲醇和酮咯酸氨丁三醇,超声溶解后使成浅黄色的澄清溶液剂,在澄清溶液剂中依次加入PH调节剂和保湿剂后,在水浴锅中加热并搅拌,冷却后得到雾化吸入剂。
9.根据权利要求8所述的一种用于宠物的雾化吸入剂的制备方法,其特征在于,所述步骤1中,缓冲液PH值为11.59,水浴锅温度设置为40℃,加热时间为10min,雾化吸入剂的PH值为7.2。
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CN1698584A (zh) * | 2005-04-30 | 2005-11-23 | 山东京卫制药有限公司 | 含活性成分的鼻喷雾凝胶剂 |
CN103655472A (zh) * | 2012-09-14 | 2014-03-26 | 南京康来福医药科技有限公司 | 一种酮咯酸氨丁三醇鼻腔喷雾剂及制备方法 |
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