CN100496491C - 治疗慢性鼻炎的甲苯咪唑新剂型 - Google Patents
治疗慢性鼻炎的甲苯咪唑新剂型 Download PDFInfo
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Abstract
本发明涉及使用甲苯咪唑制备喷雾剂、气雾剂、粉雾剂和滴鼻剂,以及这些含有甲苯咪唑的喷雾剂、气雾剂、粉雾剂和滴鼻剂在治疗慢性鼻炎中的应用。
Description
本发明涉及使用甲苯咪唑制备喷雾剂、气雾剂、粉雾剂和滴鼻剂,以及这些含有甲苯咪唑的喷雾剂、气雾剂、粉雾剂和滴鼻剂在治疗慢性鼻炎中的应用。
一、慢性鼻炎简介|
慢性鼻炎(chronic rh initis)是鼻腔粘膜和粘膜下层的慢性炎症。表现为鼻粘膜的慢性充血肿胀,称慢性单纯性鼻炎(chronic simple rhinitis)。若发展为鼻粘膜和鼻甲骨的增生肥厚,称慢性肥厚性鼻炎(chronic hypertrophic rhinitis)。
(一)病因
1.局部病因
(1)急性鼻炎反复发作或治疗不彻底而演变成慢性鼻炎。
(2)由于邻近的慢性炎症长期刺激或畸形,致鼻发生通气不畅或引流阻塞,如慢性鼻窦炎、鼻中隔偏曲、慢性扁桃体炎或腺样体肥大等。
(3)鼻腔用药不当或过量过久形成药物性鼻炎(rhinitis medicamentosa),常见于久用滴鼻净之后。
2.全身病因
(1)长期慢性疾病,如内分泌失调、长期便秘、肾脏病和心血管疾病等,而致鼻粘膜长期或屡发性充血或瘀血。
(2)维生素缺乏,如维生素A或C。
(3)烟酒过度可影响鼻粘膜血管舒缩而发生障碍。
(4)长期服用利血平等降压药物,可引起鼻腔血管扩张而产生似鼻炎的症状。
3.环境因素:在有水泥、烟草、煤尘、面粉或化学物质等环境中的工作者,鼻粘膜受到物理和化学因子的刺激与损害,可造成慢性鼻炎。温湿度急剧变化的环境,如炼钢、冷冻、烘熔等车间工人,也较易发生此病。
(二)治疗原则消炎消肿,通气引流和尽量维护鼻粘膜的生理功能,同时要注意对病因的处理。
二、慢性单纯性鼻炎
(一)病理 粘膜深层血管慢性扩张,尤以下鼻甲海绵状血窦变化最明显。粘液腺功能活跃,分泌增多。鼻甲粘膜肿胀,但粘膜下组织无明显增生性改变。
(二)临床表现
1.鼻塞:间歇性或交替性。①间歇性鼻塞:一般表现为白天、劳动或运动时减轻,夜间、静坐或寒冷时加重。②交替性鼻塞:侧卧时位于下侧的鼻腔常阻塞加重;转卧另一侧后,刚才位于上侧没有鼻塞或鼻塞较轻的鼻腔,转到下侧后出现鼻塞或鼻塞加重;而刚才位于下侧的鼻腔鼻塞减轻。此外,嗅觉可有不同程度的减退,说话呈闭塞性鼻音。由于鼻涕长期流经鼻前庭和上唇部,可致皮炎或湿疹,多见于小孩。鼻涕向后可流入咽腔,出现咳嗽、多痰等症状。
2.多涕:常为粘液性或粘脓性,偶呈脓性。脓性者多于继发性感染后出现。
3.检查:鼻粘膜肿胀,表面光滑、湿润,一般呈暗红色。鼻甲粘膜柔软而富有弹性,探针轻压可现凹陷,但移开探针则凹陷很快复原,特别在下鼻甲为明显。若用1~2%麻黄素液作鼻粘膜收缩,则鼻甲迅速缩小。总鼻道或下鼻道有粘液性或脓性分泌物。
(三)治疗治疗原则为恢复鼻腔通气功能,排除分泌物,根除病因。
1. 1%麻黄素或呋喃西林麻黄素液、氯霉素麻黄素液滴鼻,每日3次,
2. 0.25~0.5%普鲁卡因作鼻丘封闭或下鼻甲粘膜下封闭,每次1~1.5ml,隔日1次,或每周2次,5次为一疗程。
3.超短波或红外线理疗,可改善局部血循环以减轻症状。
4.经上述疗法无效时,可选用硬化剂作下鼻甲注射治疗。
5.找出与疾病有关的病因并及时治疗。锻炼身体增强机体抵抗力。
三、慢性肥厚性鼻炎
慢性肥厚性鼻炎(chronic hypertrophic rhinitis)为鼻粘膜、粘膜下层及鼻甲骨的增生肥厚性改变,一般由慢性单纯性鼻炎发展而来。
(一)病理 粘膜上皮纤毛脱落,变为复层立方上皮,粘膜下层由水肿继而发生纤维组织增生而使粘膜肥厚,久之,可呈桑椹状或息肉样变,骨膜及骨组织增生,鼻甲骨骨质也可呈肥大改变。
(二)临床表现
1.鼻塞较重,多为持续性、常张口呼吸,嗅觉多减退。
2.鼻涕稠厚,多呈粘液性或粘脓性。由于鼻涕后流,刺激咽喉致有咳嗽、多痰。
3.当肥大的中鼻甲压迫鼻中隔时,可引起三叉神经眼支所分出的筛前神经受压或炎症,出现不定期发作性额部疼痛,并向鼻梁和眼眶放射,称筛前神经痛,又称筛前神经综合症。
4.检查:①下鼻甲明显肥大,或下鼻甲与中鼻甲均肥大,常致鼻腔堵塞。鼻腔底部或下鼻道有粘液性或粘脓性分泌物。②粘膜肿胀,呈粉红色或紫红色,表面不平,或呈结节状或桑椹状,尤以下鼻甲前端及其游离缘为明显。探针轻压凹陷不明显,触之有硬实感。③局部用血管收缩剂后粘膜收缩不明显。
(三)治疗
1.血管收缩剂滴鼻液的应用,限于轻型病例。
2.下鼻甲粘膜下硬化剂注射,其作用机理为硬化剂注射后,可使局部发生化学性炎性反应,产生疤痕组织,缩小鼻甲体积,改善通气。常用50%葡萄糖液加15%氯化钠溶液、5%鱼肝油酸钠或80%甘油等。鼻甲表面麻醉后,用22~23号细长针头从下鼻甲下缘前端平行向后刺入,勿刺通粘膜,边退针边注射硬化剂,直至针头拔出为止。亦可于下鼻甲前端、中部、后端分3次注射,每侧注射0.5ml,每10天1次,以3~5次为一疗程。
3.下鼻甲粘膜下电凝固肥厚的粘膜组织,使产生疤痕收缩。在表面麻醉后,电针头从下鼻甲前端刺入,凝固20~30秒钟后拔出,电流为10~30毫安。
4.冷冻手术,是将特制的冷冻头置于下鼻甲表面做冷冻,每次1~2分钟,使病变粘膜坏死脱落而再生粘膜。
5.手术疗法,一般治疗无效,或粘膜显著肥厚,或肥厚部分位于下鼻甲后端或下缘,可行下鼻甲部分切除术或中鼻甲部分切除术。下鼻甲切除不宜过多,原则上不超过下鼻甲的1/3,以免影响鼻粘膜功能或继发萎缩性鼻炎。骨性肥大者,宜行下鼻甲粘-骨膜下切除术,既可改善鼻腔的通气引流,又无损于鼻粘膜的生理功能。
6.对全身慢性疾病或邻近病灶如鼻中隔偏曲或鼻窦炎等,亦给予适当治疗。
四、甲苯咪唑简介
甲苯咪唑,英文通用名称为Mebendazole;一般名称为:5-苯甲酰苯并咪唑氨甲酸甲酯、苯甲酰咪胺甲酯、二苯酮胍甲酯、二苯酮米胺酯、甲苯达唑、甲基咪唑等。为广谱驱虫药。可影响虫体多种生化代谢途径。本药可以抑制肠道寄生虫对葡萄糖的摄取,导致虫体内的糖原耗竭;也可与虫体微管蛋白结合抑制微管聚集,从而抑制分泌颗粒转运和其它亚细胞器运动;还可抑制虫体线粒体延胡索酸还原酶系统,减少ATP生成,从而干扰虫体生存和繁殖而导致其死亡。本药有完全杀死钩虫卵和鞭虫卵以及部分杀死蛔虫卵的作用。体外试验证明5mg/L可抑制钩虫幼虫的发育。此外,大剂量、长疗程使用本药,还有治疗旋毛虫病和包虫病的作用。人口服甲苯咪唑吸收少(5%-10%)。口服后2-5小时血药浓度达峰值,但不到服药量的0.3%。每日服用200mg,3日后血药浓度不超过0.3mg/L。药物在体内分布于血浆、肝、肺等部位,主要在肝内代谢。半衰期为2.5-5.5小时,肝功能不良(胆汁淤积)时则可达35小时。本药口服后24小时内以原形或2-氨基代谢物经消化道排泄,5%-10%随尿排泄。
五、迄今,国内外都尚未见任何将甲苯咪唑用于治疗慢性鼻炎的报道或文献记载。
本发明将甲苯咪唑作为单独的有效成分或与其它药物一起配成复方,制成鼻腔给药的剂型,这些剂型包括,但不限于:滴鼻剂、喷雾剂、气雾剂和粉雾剂。
本发明所述的用甲苯咪唑或用含甲苯咪唑的复方制成的滴鼻剂、喷雾剂、气雾剂和粉雾剂的适应症,包括,但不限于以下病症:慢性鼻炎、过敏性鼻炎、鼻息肉或鼻息肉病、鼻炎、咽炎、气管炎和支气管炎。
使用本发明所述的用甲苯咪唑或用含甲苯咪唑的复方制成的滴鼻剂、喷雾剂、气雾剂和粉雾剂,对于慢性性鼻炎患者,直接鼻腔给药,可有效地缓解相关的症状。
本发明所述的滴鼻剂、喷雾剂、气雾剂和粉雾剂,均符合《中华人民共和国药典》(2000年版二部)关于滴鼻剂、喷雾剂、气雾剂和粉雾剂的定义。
本发明所述的慢性鼻炎,是本领域的技术人员所熟知的,现代的医学书籍中有其准确的定义。其病理学改变如前所述。
通过以下实施例对本发明的甲苯咪唑滴鼻剂、喷雾剂、气雾剂和粉雾剂的制备,以及用甲苯咪唑滴鼻剂、喷雾剂、气雾剂和粉雾剂治疗慢性鼻炎的应用进行描述。需说明的是,下述实施例只是用来说明而非限制本发明,本领域技术人员所熟知的通过其他给药途径将甲苯咪唑用于治疗鼻息肉或鼻息肉病、鼻炎、咽炎、气管炎和支气管炎的技术均在本发明的范围内。
实施例1 甲苯咪唑鼻腔喷雾剂的制备
在万级环境中,将甲苯咪唑溶于生理盐水,制备成1mg/ml的溶液,加入洁尔灭,使洁尔灭的浓度为0.02%。将此药液灌装于鼻腔喷雾剂瓶中,拧上喷雾阀即得甲苯咪唑鼻腔喷雾剂。
实施例2 甲苯咪唑鼻腔气雾剂的制备
在万级环境中,将甲苯咪唑溶于生理盐水,制备成1mg/ml的溶液,加入洁尔灭,使洁尔灭的浓度为0.02%。将此药液灌装于鼻腔气雾剂瓶中,加入抛射剂,装上气雾阀,即得甲苯咪唑鼻腔气雾剂。
实施例3 甲苯咪唑鼻腔粉雾剂的制备
在万级环境中,将甲苯咪唑20mg、羟丙基纤维素(HPC)980mg、氯苄烷铵0.1mg共混合,得到均一的甲苯咪唑为1μg/mg的粉体,粉体粒径应为30~150μm,充填入硬胶囊内,得鼻腔给药甲苯咪唑粉雾剂。使用时经鼻用粉雾装置喷入给药。
实施例4 甲苯咪唑滴鼻剂的制备
在万级环境中,将甲苯咪唑溶于生理盐水,制备成1mg/ml的溶液,加入洁尔灭,使洁尔灭的浓度为0.02%。将此药液灌装于滴鼻剂瓶中,即得甲苯咪唑滴鼻剂。
实施例5 甲苯咪唑喷雾剂治疗慢性鼻炎
甲苯咪唑治疗慢性鼻炎20例,取得了显著的临床效果。
一般资料 门诊病例20例,其中男12例,女8例;年龄16~44岁,平均27岁。患者病程13个月至12年。慢性单纯性鼻炎7例,慢性肥厚性鼻炎13例。所有病例均曾接受药物治疗,3例曾接受冷冻治疗,3例曾接受激光治疗,4例曾接受下鼻甲药物注射,药物不详。
治疗方法 患者采用“实施例1”所述的甲苯咪唑喷雾剂治疗,每天鼻腔给药喷二次,疗程均为15天,期间禁用其他抗炎药物及其他类型的滴鼻剂。
疗效评价标准 以末次随访时检查情况为标准。痊愈:鼻塞症状完全消失,鼻腔完全恢复通气,鼻分泌物及嗅觉亦有改善,下鼻甲明显缩小。好转:鼻塞明显改善,仅在上呼吸道感染或侧卧时有轻微鼻塞现象,下鼻甲较治疗前有不同程度缩小。无效:随访时间内鼻塞无改善,下鼻甲无改变。
结果 两组治疗后1周、2周、1个月及3个月分别随访4次,以后不定期随访。随访时间长者9个月,最短者1个月,平均随访4个月。
慢性单纯性鼻炎7例(痊愈2例,好转4例,无效1例);有慢性肥厚性鼻炎13例(痊愈4例,好转9例,无效2例)。
实施例6 甲苯咪唑气雾剂治疗慢性鼻炎
某男,33岁,患慢性鼻炎6年,头痛、头晕、鼻塞,感冒时症状更加严重,使用“实施例2”所述的甲苯咪唑气雾剂治疗,12天后症状消失。随访30天,未见复发。以后除感冒时再无鼻炎症状。
实施例7 甲苯咪唑粉雾剂治疗慢性鼻炎个案
某女,45岁,因患感冒治疗不及时造成慢性鼻炎,鼻塞、流鼻涕,夜晚不能用鼻呼吸,只能用口呼吸。用“实施例3”所述的甲苯咪唑粉雾剂治疗,每天一次,持续15天,鼻塞的症状全部消失,治疗2周后,慢性鼻炎症状全部消失。
实施例8 甲苯咪唑滴鼻剂治疗慢性鼻炎个案
某男,33岁,慢性鼻烟病史6年,鼻塞,头晕头痛,用“实施例4”所述的甲苯咪唑滴鼻剂行滴鼻治疗,每天一次,持续15天,从用药第5天起,症状逐日减轻。继续同法使用甲苯咪唑滴鼻剂,10天后复查,症状完全消失。
Claims (1)
1、甲苯咪唑在制备治疗慢性鼻炎的药物中的应用。
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单剂量甲苯达唑对桑西巴土源性线虫流行与感染度的影响. 沈继龙等.国外医学.寄生虫病分册,第22卷第4期. 1995 |
单剂量甲苯达唑对桑西巴土源性线虫流行与感染度的影响. 沈继龙等.国外医学.寄生虫病分册,第22卷第4期. 1995 * |
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