本文選題：曲安奈德 + 羥丙基-β-環(huán)糊精　； 參考：《遼寧大學(xué)》2017年碩士論文

【摘要】：過(guò)敏性鼻炎(Allergic Rhinitis AR)是一種由多種致敏源引起的免疫球蛋白IgE介導(dǎo)的機(jī)體炎癥反應(yīng),主要臨床表現(xiàn)為鼻塞、鼻癢、流鼻涕、打噴嚏等,嚴(yán)重影響患者的正常生活。使用鼻噴霧劑是治療過(guò)敏性鼻炎,緩解癥狀的主要方法。環(huán)糊精是超分子化學(xué)的重要組成部分,可以與疏水性藥物通過(guò)非共價(jià)鍵形成超分子包合物。超分子藥物具有溶解度好,生物利用度高,毒性低等優(yōu)點(diǎn)。曲安奈德是一種強(qiáng)效糖皮質(zhì)激素,是治療過(guò)敏性鼻炎的首選藥物,具有很好的治療效果和較弱的不良反應(yīng)。由于曲安奈德的溶解性較差,故目前國(guó)內(nèi)外上市的曲安奈德鼻噴霧劑均為混懸劑。藥物振搖后混合不均勻,藥物均一度較差,而且沒(méi)有從根本上解決曲安奈德溶解性差的問(wèn)題。故本課題選用環(huán)糊精作為包合材料,使之與曲安奈德形成超分子包合物,增加曲安奈德的溶解度。溶液型曲安奈德鼻噴霧劑在鼻腔內(nèi)具有更好的鋪展性,可以促進(jìn)曲安奈德在鼻腔內(nèi)的吸收,從而提高藥物的生物利用度。本文研究了曲安奈德的理化性質(zhì),選用羥丙基-β-環(huán)糊精和磺丁基-β-環(huán)糊精兩種β-環(huán)糊精衍生物作為包合材料,形成曲安奈德環(huán)糊精超分子包合物,以包合率為指標(biāo),確定主客分子投料比以及最佳制備工藝;采用冷凍干燥法制備曲安奈德環(huán)糊精超分子包合物固體,并通過(guò)表征和光譜研究驗(yàn)證曲安奈德與環(huán)糊精形成超分子包合物。在曲安奈德環(huán)糊精超分子包合物水溶液制備的基礎(chǔ)上,參考賽諾菲的產(chǎn)品(Nasacort AQ),確定輔料的種類,根據(jù)粘度和毫摩爾滲透壓為指標(biāo),確定了生物粘附劑HPMC和滲透壓調(diào)節(jié)劑無(wú)水葡萄糖的用量,篩選得到曲安奈德環(huán)糊精超分子包合物鼻噴霧劑的處方;通過(guò)特征性對(duì)比研究,確定曲安奈德環(huán)糊精超分子包合物鼻噴霧劑優(yōu)于觸變性曲安奈德鼻噴霧劑。通過(guò)二甲苯致小鼠耳廓腫脹模型和角叉菜膠致大鼠足爪腫脹模型試驗(yàn)考察曲安奈德環(huán)糊精超分子包合物鼻噴霧劑對(duì)腫脹模型的影響,實(shí)驗(yàn)結(jié)果表明,曲安奈德環(huán)糊精超分子包合物鼻噴霧劑對(duì)急性炎癥有治療作用;通過(guò)建立豚鼠過(guò)敏性鼻炎模型,來(lái)考察曲安奈德環(huán)糊精超分子包合物鼻噴霧劑對(duì)過(guò)敏性鼻炎的影響,實(shí)驗(yàn)結(jié)果表明,曲安奈德環(huán)糊精超分子包合物鼻噴霧劑對(duì)過(guò)敏性鼻炎藥效明顯,中劑量組和高劑量組藥效優(yōu)于陽(yáng)性對(duì)照藥。
[Abstract]:Allergic rhinitis Allergic Rhinitis ARA is an immunoglobulin IgE mediated inflammatory response caused by various allergens. Its main clinical manifestations are nasal congestion, itching, runny nose, sneezing and so on, which seriously affect the normal life of patients. Nasal spray is the main way to treat allergic rhinitis and relieve symptoms. Cyclodextrin is an important component of supramolecular chemistry and can form supramolecular inclusion complexes with hydrophobic drugs through non-covalent bonds. Supramolecular drugs have the advantages of good solubility, high bioavailability and low toxicity. Triamcinolone acetonide is a powerful glucocorticoid and is the first choice in the treatment of allergic rhinitis. Because of the poor solubility of triamcinolone acetonide, triamcinolone acetonide nasal spray is a suspension. After shaking, the mixture was uneven, the drug was once poor, and the problem of poor solubility of triamcinolone acetonide was not fundamentally solved. Therefore, cyclodextrin was chosen as inclusion material to form supramolecular inclusion compound with triamcinolone acetonide, and the solubility of triamcinolone acetonide was increased. The solution type triamcinolone acetonide nasal spray has better spread in the nasal cavity, can promote the triamcinolone acetonide absorption in the nasal cavity, thus enhances the bioavailability of the drug. The physical and chemical properties of triamcinolone acetonide were studied. Two 尾 -cyclodextrin derivatives, hydroxypropyl- 尾 -cyclodextrin and Ding Ji-尾 -cyclodextrin, were used as inclusion materials to form triamcinolone acetonide cyclodextrin supramolecular inclusion complex. The supermolecular inclusion complex of triamcinolone acetonide cyclodextrin was prepared by freeze-drying method, and the supramolecular inclusion complex between triamcinolone acetonide and cyclodextrin was confirmed by characterization and spectroscopic study. Based on the preparation of triamcinolone acetonide cyclodextrin supramolecular inclusion complex aqueous solution and referring to the product of Sanofir, Nasacort AQA, the types of excipients were determined, and the viscosity and molar osmotic pressure were used as indexes. The dosage of bioadhesive HPMC and osmotic pressure regulator anhydrous glucose was determined and the formulation of triamcinolone acetonide cyclodextrin inclusion compound nasal spray was obtained. It was determined that triamcinolone acetonide cyclodextrin inclusion compound nasal spray was superior to thixotropic triamcinolone acetonide nasal spray. The effects of triamcinolone acetonide cyclodextrin inclusion compound nasal spray on the swelling model of mouse auricle and rat paw induced by carrageenin were studied. The nasal spray of triamcinolone acetonide cyclodextrin inclusion compound has a therapeutic effect on acute inflammation and the effect of triamcinolone acetonide cyclodextrin inclusion compound nasal spray on allergic rhinitis was investigated by establishing a guinea pig allergic rhinitis model. The results showed that triamcinolone acetonide cyclodextrin supramolecular inclusion compound nasal spray had obvious effect on allergic rhinitis.
【學(xué)位授予單位】：遼寧大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R943

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