本文選題：酮咯酸氨丁三醇 + 即型凝膠��； 參考：《黑龍江中醫(yī)藥大學(xué)》2014年碩士論文

【摘要】：近年來(lái),鼻腔給藥以其吸收迅速、給藥方便和避免首過(guò)效應(yīng)等優(yōu)點(diǎn)引起了廣泛的關(guān)注,研究日益深入,應(yīng)用不斷拓展。即型凝膠其兼具溶液劑給藥方便與凝膠劑長(zhǎng)久滯留的優(yōu)點(diǎn),在緩控釋遞藥領(lǐng)域有著廣闊的應(yīng)用前景,在鼻腔給藥中的重要性和實(shí)用性尤其凸顯。 非甾體抗炎藥酮咯酸氨丁三醇(Ketorolac Tromethamine,簡(jiǎn)稱(chēng)Ket)在手術(shù)后中重度疼痛控制方面療效確切,但臨床上目前以注射給藥為主,雖亦有鼻腔用溶液制劑上市,但在鼻腔內(nèi)流失快,滯留短,吸收不充分,給藥頻繁,給患者帶來(lái)不便。為了改善酮咯酸氨丁三醇鼻腔給藥的藥代動(dòng)力學(xué)特征,本論文制備了基于卡拉膠-泊洛沙姆407復(fù)合溫敏凝膠體系(carrageenan-poloxamer407hydrogel, CPH)的酮咯酸氨丁三醇鼻腔溫敏即型凝膠,對(duì)其進(jìn)行了較為系統(tǒng)的體內(nèi)外表征。 在體外表征部分,本文考察了載酮咯酸氨丁三醇的卡拉膠-泊洛沙姆407復(fù)合溫敏凝膠(簡(jiǎn)稱(chēng)Ket-CPH)的溶蝕特征、釋藥行為以及流變學(xué)性質(zhì),著重考察了Ket載藥濃度對(duì)CPH溶蝕速度、釋藥速度以及凝膠化溫度的影響。結(jié)果表明,Ket-CPH具有一定的藥物緩釋能力。Ket濃度越高,凝膠溶蝕越快,藥物釋放速度越快。Ket-CPH凝膠化溫度亦隨Ket濃度的增大而升高,其溫度敏感性相轉(zhuǎn)變行為符合給藥的實(shí)際需要,當(dāng)Ket含量為15%(w/w)時(shí),CPH的凝膠化溫度約為33℃,可在鼻腔內(nèi)溫度刺激下順利發(fā)生凝膠化,在室溫下粘度低,便于給藥,且該載藥濃度與市售鼻腔制劑相同,因此選其進(jìn)行進(jìn)一步體內(nèi)評(píng)價(jià)。 Ket-CPH的體內(nèi)評(píng)價(jià)包括藥代動(dòng)力學(xué)研究和安全性考察兩大方面。大鼠鼻腔給予Ket-CPH后的藥代動(dòng)力學(xué)數(shù)據(jù)表明,Ket-CPH鼻腔給藥后的藥時(shí)曲線曲線下面積(AUC)顯著高于溶液組,平均滯留時(shí)間(MRT)顯著延長(zhǎng)(p0.05),而血藥濃度達(dá)峰時(shí)間相似,提示CPH這一給藥系統(tǒng)形式有利于提高Ket在鼻腔的吸收程度,具有一定的體內(nèi)緩釋效果,而對(duì)吸收速度影響不大。在蟾蜍上腭模型上進(jìn)行的鼻纖毛毒性研究結(jié)果表明,CPH凝膠基質(zhì)本身以及Ket-CPH對(duì)纖毛形態(tài)均無(wú)明顯影響,無(wú)明顯鼻腔刺激性。 綜上所述,Ket-CPH是一種方便、安全的鼻腔緩釋給藥系統(tǒng),有利于迅速、充分、持久的藥物吸收。本文工作為用于鼻腔給藥的Ket-CPH研究的進(jìn)一步開(kāi)展奠定了良好基礎(chǔ)。
[Abstract]:In recent years, nasal administration has attracted wide attention due to its advantages of rapid absorption, ease of administration and avoidance of first-pass effect. The gel has the advantages of convenient administration of solution agent and long retention of gel. It has a broad application prospect in the field of slow and controlled delivery of drugs, especially in nasal administration of the importance and practicability. Ketorolac Tromethamine (Ketorolac Tromethamine), a non-steroidal anti-inflammatory drug, is effective in the treatment of moderate and severe pain after surgery. The absorption is not sufficient, the drug is given frequently, bring inconvenience to the patient. In order to improve the pharmacokinetic characteristics of ketorolac aminobutanol in nasal administration, a temperature-sensitive ketobutanol nasal thermo-sensitive gel based on carrageenan-poloxamer407hydrogel (CPHH) was prepared in this paper, which was composed of carrageenan-poloxamer 407hydrogelatin (CPHG), carrageenan-poloxamer 407hydrogelatin (CPHG). The internal and external signs were systematically carried out. In the part of in vitro characterization, the dissolution characteristics, drug release behavior and rheological properties of carrageenan-Poloxamer 407 complex thermosensitive gel (Ket-CPH) were investigated, with emphasis on the dissolution rate of CPH by the concentration of Ket. The effect of release rate and gelation temperature. The results showed that the higher the concentration of Ket-CPH, the faster the gel dissolution and the faster the release rate. The gelation temperature of Ket-CPH also increased with the increase of Ket concentration, and the temperature sensitive phase transition behavior was in line with the actual need of drug administration. When the content of Ket is 15% / w, the gelation temperature of Ket is about 33 鈩，

本文編號(hào)：1797150