本文選題：太赫茲時域光譜 + 傅里葉變換拉曼光譜��； 參考：《中國計量學(xué)院》2016年碩士論文

【摘要】：太赫茲光譜對物質(zhì)的分子構(gòu)型、分子間作用力十分敏感;而拉曼光譜對分子內(nèi)化學(xué)鍵和官能團(tuán)的振動更有效。本文依據(jù)含氮雜環(huán)類藥物(呋喃妥因和吡嗪酰胺-異煙肼聯(lián)用藥物)在這兩種特征光譜中的特征峰,達(dá)到辨別并分析藥物晶型結(jié)構(gòu)的目的。結(jié)合實驗光譜與理論模擬結(jié)果研究氫鍵對該類含氮雜環(huán)藥物晶型結(jié)構(gòu)的影響以及相關(guān)共晶體的結(jié)構(gòu)性質(zhì);利用太赫茲波段內(nèi)聯(lián)用藥物吸收系數(shù)、折射率等與其含量的相關(guān)性研究,獲得其中吡嗪酰胺的含量檢出限。呋喃妥因是廣譜抗菌藥,存在多種晶型,水溶性差。使用傅里葉拉曼(FT-Raman)和太赫茲(THz)光譜技術(shù)研究并確認(rèn)呋喃妥因及其水合物的晶型結(jié)構(gòu)。發(fā)現(xiàn)兩者在THz光譜中的差異遠(yuǎn)高于Raman的光譜結(jié)果。呋喃妥因共晶體的水溶性高于它本身,選取呋喃妥因和5種典型的共晶形成物(3-氨基苯甲酸、4-氨基苯甲酸、馬來酸、富馬酸、尿素)制備共晶體,并通過THz技術(shù)獲得它們的指紋譜。結(jié)合DFT理論對模型藥物進(jìn)行光譜模擬,從實驗結(jié)果與理論模擬的吻合程度判斷并確認(rèn)模型藥物的晶型結(jié)構(gòu)。以呋喃妥因與4-氨基苯甲酸的共晶體為例,深入分析研磨時間對共晶體形成的動態(tài)過程的影響。共晶體與原料藥的拉曼峰和研磨反應(yīng)時間呈現(xiàn)相關(guān)性,結(jié)果表明共晶體的動態(tài)形成過程可以被特征光譜技術(shù)實時監(jiān)測。人體對吡嗪酰胺和異煙肼容易產(chǎn)生耐藥性;而吡嗪酰胺的肝臟毒性較強(qiáng),應(yīng)嚴(yán)格控制含量。利用THz光譜分析吡嗪酰胺的兩種多晶型,結(jié)合理論模擬確認(rèn)它們以二聚體形態(tài)存在。獲取異煙肼的THz光譜并驗證異煙肼以單分子形態(tài)存在。吡嗪酰胺-異煙肼聯(lián)用藥物的吸收系數(shù)、折射率與含量之間存在線性相關(guān)。本文分別采用一元線性和偏最小二乘回歸模型完成了聯(lián)用藥物的定量分析。結(jié)果表明吡嗪酰胺的偏最小二乘回歸模型的檢出極限0.7660%,是一元線性回歸的十分之一。說明偏最小二乘回歸模型的預(yù)估效果更好。
[Abstract]:The terahertz spectrum is very sensitive to the molecular configuration and intermolecular force, while the Raman spectrum is more effective for the intramolecular chemical bond and functional group vibration. Based on the characteristic peaks of nitrogen-containing heterocyclic drugs (furantoin and pyrazinamide isoniazid) in these two characteristic spectra, the crystal structure of the drugs was identified and analyzed. The effect of hydrogen bond on the crystal structure of the nitrogen-containing heterocyclic drugs and the structural properties of the related eutectic were studied by combining the experimental spectra and theoretical simulation results, and the absorption coefficients of the drugs used for inlining in the terahertz band were used. The detection limit of pyrazinamide was obtained by studying the correlation between refractive index and content of pyrazinamide. Furantoin is a broad-spectrum antimicrobial drug with many crystal forms and poor water solubility. The crystal structure of furantoin and its hydrate was studied and confirmed by Fourier Raman spectroscopy (FT-Raman) and terahertz (THz) spectroscopy. It is found that the difference between the two in THz spectra is much higher than that in Raman spectra. The water solubility of furantoin eutectic is higher than that of itself. Furantoin and five typical eutectic formatives, such as 3-aminobenzoic acid, maleic acid, fumaric acid and urea, are selected to prepare eutectic. Their fingerprints were obtained by THz technique. Combined with DFT theory, the model drug was simulated by spectrum, and the crystal structure of the model drug was confirmed by judging the degree of agreement between the experimental results and the theoretical simulation. Taking the eutectic of furantoin and 4-aminobenzoic acid as an example, the effect of grinding time on the dynamic process of eutectic formation was analyzed. The results show that the dynamic formation process of eutectic can be monitored by characteristic spectrum technique in real time. It is easy to develop drug resistance to pyrazinamide and isoniazid in human body, while pyrazinamide is more toxic in liver, so the content of pyrazinamide should be strictly controlled. Two kinds of polycrystalline forms of pyrazinamide were analyzed by THz spectroscopy, and they were confirmed to exist in dimer form by theoretical simulation. The THz spectra of isoniazid were obtained and the existence of isoniazid as a monolayer was confirmed. There is a linear correlation between the absorption coefficient, refractive index and content of pyrazinamide-isoniazid. In this paper, the linear and partial least square regression models were used to analyze the combined drugs. The results show that the detection limit of the partial least square regression model of pyrazinamide is 0. 7660, which is 1/10 of the linear regression. It shows that the prediction effect of partial least squares regression model is better.
【學(xué)位授予單位】：中國計量學(xué)院
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2016
【分類號】：R917

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