發(fā)布時間：2018-07-27 14:03

【摘要】：常年性變應性鼻炎又俗稱過敏性鼻炎，屬于常見的發(fā)生在鼻腔部位的變態(tài)反應性疾病。當過敏物質(zhì)和易敏性體質(zhì)碰觸后,引起了鼻粘膜的損傷。常見的臨床表現(xiàn)有：鼻塞、鼻癢、發(fā)作性噴嚏、清涕，并且呈現(xiàn)出季節(jié)性發(fā)作特點。 目前治療常年性變應性鼻炎的藥物主要有：糖皮質(zhì)激素（如糠酸莫米松）、抗組胺藥（如西替利嗪）、肥大細胞抑制藥（如色甘酸鈉）、血管收斂藥（如去氧腎上腺素、羥甲唑啉）、抗膽堿能藥物（如異丙托溴銨），其中由于糖皮質(zhì)激素對常年性變應性鼻炎的臨床病狀作用效果顯著，方便攜帶和使用，全身副作用小，而被普遍用于治療常年性變應性鼻炎。 本課題以糠酸莫米松鼻噴霧劑的主藥—以糠酸莫米松為模型藥物。以甘油、聚山梨酯-80、枸櫞酸鈉、枸櫞酸、苯扎氯銨、微晶纖維素-羧甲基醚纖維素鈉鹽為輔料，研制了糠酸莫米松鼻噴霧劑制劑。我們對糠酸莫米松鼻噴霧劑進行了以下的研究工作： 首先我們對糠酸莫米松鼻噴霧劑進行處方工藝研究：擇適宜的pH調(diào)節(jié)劑、防腐劑、保濕劑、助懸劑等，并對羧甲基醚纖維素鈉鹽、枸櫞酸、微晶纖維素的用量進行了篩選。通過對鼻噴霧劑的外觀性狀、pH值、沉降體積比等指標的評價，確定了優(yōu)選處方。 其次我們對糠酸莫米松鼻噴霧劑進行了質(zhì)量研究：按照糠酸莫米松鼻噴霧劑進口藥品注冊標準的相關要求。我們對糠酸莫米松鼻噴霧劑進行相關研究，以鑒別、有關物質(zhì)、每噴主藥含量、微生物限度、性狀、含量等為主要考察指標，選用高效液相色譜法來測定有關物質(zhì)、糠酸莫米松含量，防腐劑含量以及每噴主藥含量，并對含量和防腐劑含量及有關物質(zhì)的測定方法進行了方法學驗證，并建立了一整套控制糠酸莫米松鼻噴霧劑質(zhì)量的檢測標準。為用藥的有效性以及安全性提供了實驗根據(jù)。實驗結果表明研制的糠酸莫米松鼻噴霧劑的主要考察指標均符合規(guī)定。 然后我們對糠酸莫米松鼻噴霧劑進行了穩(wěn)定性研究。穩(wěn)定性研究是質(zhì)量研究中非常重要的一個環(huán)節(jié)，是研究藥物在物理、化學等特性變化的情況。本實驗從影響因素（高濕、高溫、光照）、加速6個月穩(wěn)定性、長期9個月穩(wěn)定性三個方面對糠酸莫米松鼻噴霧劑進行初步考察，實驗結果顯示：糠酸莫米松鼻噴霧劑穩(wěn)定性良好,其貯藏條件為避光，2-25℃。 最后我們對糠酸莫米松鼻噴霧劑進行了皮膚過敏性和刺激性研究。藥理毒理研究是體現(xiàn)藥物在使用時對人體產(chǎn)生不良反應以及不良反應程度的情況。對家兔鼻粘膜組織以及呼吸道局部（鼻、喉、氣管、支氣管）粘膜組織的進行刺激性評價以及對豚鼠皮膚進行過敏性評價，結果表明研制的糠酸莫米松鼻噴霧劑對家兔鼻粘膜組織以及呼吸道局部（鼻、喉、氣管、支氣管）粘膜組織無刺激性，對豚鼠皮膚無致敏性。
[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，

本文編號：2148060