糠酸莫米松鼻喷雾剂的研制及质量研究

发布时间：2018-07-27 14:03

【摘要】：常年性变应性鼻炎又俗称过敏性鼻炎，属于常见的发生在鼻腔部位的变态反应性疾病。当过敏物质和易敏性体质碰触后,引起了鼻粘膜的损伤。常见的临床表现有：鼻塞、鼻痒、发作性喷嚏、清涕，并且呈现出季节性发作特点。 目前治疗常年性变应性鼻炎的药物主要有：糖皮质激素（如糠酸莫米松）、抗组胺药（如西替利嗪）、肥大细胞抑制药（如色甘酸钠）、血管收敛药（如去氧肾上腺素、羟甲唑啉）、抗胆碱能药物（如异丙托溴铵），其中由于糖皮质激素对常年性变应性鼻炎的临床病状作用效果显著，方便携带和使用，全身副作用小，而被普遍用于治疗常年性变应性鼻炎。 本课题以糠酸莫米松鼻喷雾剂的主药—以糠酸莫米松为模型药物。以甘油、聚山梨酯-80、枸橼酸钠、枸橼酸、苯扎氯铵、微晶纤维素-羧甲基醚纤维素钠盐为辅料，研制了糠酸莫米松鼻喷雾剂制剂。我们对糠酸莫米松鼻喷雾剂进行了以下的研究工作： 首先我们对糠酸莫米松鼻喷雾剂进行处方工艺研究：择适宜的pH调节剂、防腐剂、保湿剂、助悬剂等，并对羧甲基醚纤维素钠盐、枸橼酸、微晶纤维素的用量进行了筛选。通过对鼻喷雾剂的外观性状、pH值、沉降体积比等指标的评价，确定了优选处方。 其次我们对糠酸莫米松鼻喷雾剂进行了质量研究：按照糠酸莫米松鼻喷雾剂进口药品注册标准的相关要求。我们对糠酸莫米松鼻喷雾剂进行相关研究，以鉴别、有关物质、每喷主药含量、微生物限度、性状、含量等为主要考察指标，选用高效液相色谱法来测定有关物质、糠酸莫米松含量，防腐剂含量以及每喷主药含量，并对含量和防腐剂含量及有关物质的测定方法进行了方法学验证，并建立了一整套控制糠酸莫米松鼻喷雾剂质量的检测标准。为用药的有效性以及安全性提供了实验根据。实验结果表明研制的糠酸莫米松鼻喷雾剂的主要考察指标均符合规定。 然后我们对糠酸莫米松鼻喷雾剂进行了稳定性研究。稳定性研究是质量研究中非常重要的一个环节，是研究药物在物理、化学等特性变化的情况。本实验从影响因素（高湿、高温、光照）、加速6个月稳定性、长期9个月稳定性三个方面对糠酸莫米松鼻喷雾剂进行初步考察，实验结果显示：糠酸莫米松鼻喷雾剂稳定性良好,其贮藏条件为避光，2-25℃。 最后我们对糠酸莫米松鼻喷雾剂进行了皮肤过敏性和刺激性研究。药理毒理研究是体现药物在使用时对人体产生不良反应以及不良反应程度的情况。对家兔鼻粘膜组织以及呼吸道局部（鼻、喉、气管、支气管）粘膜组织的进行刺激性评价以及对豚鼠皮肤进行过敏性评价，结果表明研制的糠酸莫米松鼻喷雾剂对家兔鼻粘膜组织以及呼吸道局部（鼻、喉、气管、支气管）粘膜组织无刺激性，对豚鼠皮肤无致敏性。
[Abstract]:Perennial allergic rhinitis, also known as allergic rhinitis, is a common allergic disease occurring in the nasal cavity. When the allergic substances and susceptibility to physical contact, causing nasal mucosal damage. Common clinical manifestations are: nasal obstruction, itching, sneezing, snot, and seasonal attack. Currently, the main drugs used to treat perennial allergic rhinitis include glucocorticoids (such as amethasone furoate), antihistamines (such as cetirizine), mast cell suppressor drugs (such as sodium chromoglycate), vasoconvergent drugs (e.g., noradrenaline, etc.). Hydroxymethazoline), an anticholinergic drug (such as ipratropium bromide), in which glucocorticoids have a significant effect on clinical symptoms of perennial allergic rhinitis, are easy to carry and use, and have little systemic side effects. It is commonly used in the treatment of perennial allergic rhinitis. In this paper, the main drug of momethasone furoate nasal spray-amethasone furoate as model drug. With glycerol, polysorbate-80, sodium citrate, citric acid, benzalkonium chloride, microcrystalline cellulose-carboxymethyl ether cellulose sodium salt as excipient, the preparation of momethasone furoate nasal spray was prepared. We have done the following research work on the momethasone furoate nasal spray: first, we studied the prescription technology of the momethasone furoate nasal spray: selecting suitable pH regulator, preservative, moisturizer, suspending agent, etc. The amount of sodium carboxymethyl ether cellulose, citric acid and microcrystalline cellulose were screened. The optimum prescription was determined by evaluating the appearance character and sedimentation volume ratio of nasal spray. Secondly, we studied the quality of momethasone furoate nasal spray: according to the requirements of import drug registration standard of momethasone furoate nasal spray. In order to identify the related substances, the content of each main drug, microbial limit, character, content, etc., were used to determine the related substances by high performance liquid chromatography (HPLC). The content of momethasone furoate, the content of preservative and the content of the main drug per spray were verified, and the method of determination of the content and the content of preservative and related substances were verified, and a set of standards for the determination of the quality of the nasal spray of momethasone furoate were established. It provides experimental basis for the efficacy and safety of the drug. The experimental results showed that the main indexes of momethasone furoate nasal spray were in accordance with the regulations. Then we studied the stability of momethasone furoate nasal spray. Stability study is a very important part of quality research, which is to study the changes of physical and chemical properties of drugs. In this experiment, the effect factors (high humidity, high temperature, illumination), accelerating stability for 6 months, and long-term stability for 9 months were studied for momethasone furoate nasal spray. The results showed that the stability of momethasone furoate nasal spray was good, and the storage condition was 2-25 鈩，

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