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  本文關(guān)鍵詞：雙胍和季銨鹽殼聚糖藥物控釋體系的制備與表征　出處：《華南農(nóng)業(yè)大學(xué)》2016年碩士論文　論文類型：學(xué)位論文

  更多相關(guān)文章： 殼聚糖衍生物 載藥微膠囊 木質(zhì)素磺酸鈉 海藻酸鈉 水凝膠微球 緩釋

【摘要】：殼聚糖(CS)是甲殼素脫乙�；蟮玫降囊环N天然陽離子多糖,具有良好的生物相容性、抑菌性及抗氧化性。以CS為主的藥物緩釋體系,不僅能改善被包載藥物的化學(xué)穩(wěn)定性,延長藥效,而且對環(huán)境和人體無毒且易降解,在現(xiàn)代農(nóng)業(yè)與生物醫(yī)藥領(lǐng)域都有良好應(yīng)用前景。本論文研究了三種CS及衍生物的藥物緩釋體系,主要研究結(jié)果如下:在第一部分中,以未改性CS作對照,分別以兩種改性殼聚糖,雙胍殼聚糖(BGCS)及季銨鹽殼聚糖(HTCC)為壁材,吲哚-3-乙酸(IAA)為藥物模型,通過乳化交聯(lián)法制備并表征了兩種載藥微膠囊(MCs)緩釋體系,并研究了它們的藥物釋放機理。首先對CS進(jìn)行化學(xué)改性,制備了取代度不同的BGCS和HTCC,并選取取代度較低的改性殼聚糖作為載藥壁材。然后通過單因素實驗,分別考察了壁材濃度、交聯(lián)劑的用量、交聯(lián)時間以及油相/水相比例對載IAA的包封率(EE)的影響。并采用了IR、UV-vis、TGA以及SEM等手段對IAA-MCs進(jìn)行了化學(xué)結(jié)構(gòu)、熱穩(wěn)定性及表觀形貌表征。結(jié)果表明:在載藥能力和熱穩(wěn)定性方面,以兩種改性CS壁材所制備的載藥MCs均優(yōu)于未改性CS,其中BGCS-MCs比HTCC-MCs具有更光滑緊致的表面形貌和更小的平均粒徑(6.69μm)。在釋藥動力學(xué)研究中發(fā)現(xiàn),三種MCs在水中的釋放量均比在甲醇中大;和CS-MCs及BGCS-MCs相比,HTCC-MCs明顯改善了突釋現(xiàn)象。根據(jù)對三種CS-MCs的釋藥動力學(xué)模型的數(shù)學(xué)擬合發(fā)現(xiàn),三種MCs的藥物釋放動力學(xué)方程均符合Korsmeyer-Peppas模型,且在水和甲醇介質(zhì)中的釋藥過程均為Fickian擴散。在第二部分中,在改性CS-MCs壁材中加入聚陰離子型高分子材料木質(zhì)素磺酸鈉(SL),以1-萘乙酸甲酯(MNAA)為藥物模型,采用復(fù)凝聚法制備了包載MNAA的MCs:BGCS/SL-MCs、HTCC/SL-MCs和CS/SL-MCs。通過單因素試驗考察了CS及其衍生物的濃度、SL的濃度、芯壁比以及復(fù)凝聚時的pH對微膠囊EE的影響。同時用IR、UV-vis、TGA以及SEM對三種載藥MCs的性質(zhì)及表觀形貌進(jìn)行了表征。結(jié)果表明:在CS的氨基位引入強正電子基團(tuán),與聚陰離子性高分子材料SL產(chǎn)生更強的靜電作用,故改性CS壁材制備的載藥微膠囊具有穩(wěn)定的化學(xué)結(jié)構(gòu)、更高的包封率和熱穩(wěn)定性;在藥物緩釋機理研究中,BGCS/SL-MCs的緩釋效果最佳,三組MCs的釋放程度均隨著環(huán)境溫度升高而加大,且動力學(xué)緩釋模型均屬于Korsmeyer-Peppas模型。在第三部分中,在海藻酸鈉水凝膠(SA-HG)載藥體系中,引入改性CS以提高藥物包封率和釋藥可控性。采用擠出-外源凝膠法,以CaCl2做交聯(lián)劑,以5-氟尿嘧啶(5-FU)為藥物模型,以CS為對照,將BGCS或HTCC與SA復(fù)合制備載5-FU的水凝膠球(HGBs)——CS/SA-HGBs、BGCS/SA-HGBs和HTCC/SA-HGBs。通過IR、UV-vis和TGA表征了凝膠球的物理化學(xué)性能,并測試其溶脹性與釋藥性。首先采用單因素確定制備成球的最優(yōu)化條件:改性CS濃度0.5%,SA濃度3%,CaCl2濃度2%;與CS/SA-HGBs對照,BGCS/SA-HGBs和HTCC/SA-HGBs的EE分別提高了7.58%和11.0%。這是因為CS壁材改性后,引入的雙胍或季銨基與SA上的羧基形成較強的氫鍵,因此提升了HGBs的熱穩(wěn)定性、機械性能和保水性。藥物緩釋實驗結(jié)果表明,三種CS/SA-HGBs的溶脹率和藥物釋放速率均隨pH變化發(fā)生規(guī)律性改變,因此具有良好的pH響應(yīng)性;其緩釋效果的強弱順序為:HTCC/SA-HGBs,BGCS/SA-HGBs,HTCC/SA-HGBs。
[Abstract]:Chitosan (CS) is a natural cationic deacetylated chitin obtained polysaccharide has good biocompatibility, antibacterial and antioxidant activity. The drug delivery system based on CS, can not only improve the chemical stability of loaded drug and extend the efficacy, non-toxic to environment and human body and easy degradation, have good application prospect in modern agricultural and biological medicine. This thesis drug delivery system and three kinds of CS derivatives, the main results are as follows: in the first part, with the unmodified CS as control, respectively to two kinds of modified chitosan biguanide chitosan (BGCS) and quaternary ammonium salt of chitosan (HTCC) as wall material, indole -3- acetic acid (IAA) as drug model, through the emulsion crosslinking method of two kinds of drug loaded microcapsules preparation and characterization of (MCs) delivery system, and study their drug release mechanism. Firstly, CS was chemically modified, was prepared to replace Different degrees of BGCS and HTCC, and select the degree of substitution of modified chitosan with low drug loading as wall material. Then through the single factor experiment were investigated, wall material concentration, the amount of crosslinking agent, crosslinking time and oil / aqueous phase ratio of IAA encapsulation efficiency (EE) and the influence. Using IR, UV-vis, TGA, SEM and other means of the chemical structure of IAA-MCs, and the apparent morphology characterization of thermal stability. The results showed that: in the drug loading capacity and thermal stability, with two kinds of modified CS wall material prepared by loading MCs were better than that of unmodified CS, BGCS-MCs than HTCC-MCs with the surface morphology and the smaller is more smooth and compact with the average diameter (6.69 m). Found in the drug release kinetics study, three kinds of MCs release in the water than in methanol; compared with CS-MCs and BGCS-MCs, HTCC-MCs significantly improved the burst release phenomenon. According to the three release of CS-MCs pharmacokinetic model Mathematical fitting found that drug release kinetics of three kinds of MCs were consistent with the Korsmeyer-Peppas model, and in water and methanol in the medium of drug release process was the diffusion of Fickian. In the second part, adding a polyanionic material of sodium lignosulfonate in modified CS-MCs wall material (SL), 1- (naphthylacetate MNAA) as a model drug, using complex coacervation MNAA loaded MCs:BGCS/SL-MCs was prepared, HTCC/SL-MCs and CS/SL-MCs. were investigated through the single factor test the concentration of CS and its derivatives, the concentration of SL, and the influence of the ratio of core to wall complex coacervation pH on the micro capsule of EE. At the same time with the IR, UV-vis, TGA and SEM on three kinds of drug loaded MCs properties and surface morphology were investigated. The results showed that: in the introduction of strong amino CS positron group, produce stronger electrostatic interaction with poly anionic polymer material SL, the modified CS drug loaded microcapsules wall material preparation Has stable chemical structure, higher encapsulation efficiency and thermal stability; in the study of mechanism of drug release, sustained release effect of BGCS/SL-MCs is best, the release degree of three groups of MCs were increased as the ambient temperature increases, and the dynamics of releasing model belong to the Korsmeyer-Peppas model. In the third part, the sodium alginate hydrogel (SA-HG) carrier delivery system, the introduction of modified CS to improve the drug encapsulation efficiency and drug release control. By extrusion - exogenous gel method, using CaCl2 as crosslinking agent, 5- fluorouracil (5-FU) as drug model, compared with CS, BGCS or HTCC hydrogel microparticles and SA compound preparation containing 5-FU (HGBs CS/SA-HGBs, BGCS/SA-HGBs and HTCC/SA-HGBs.) by IR, UV-vis and TGA were used to characterize the physical and chemical properties of gel beads, and test the swelling and drug release. First determine the preparation conditions by single factor optimization ball: modified CS concentration 0.5%, SA The concentration of 3%, the concentration of CaCl2 2%; compared with CS/SA-HGBs, BGCS/SA-HGBs and HTCC/SA-HGBs EE were increased by 7.58% and 11.0%. this is because the CS wall material modified into double guanidine or Ji Anji and SA on the formation of a strong hydrogen bond of carboxyl, thus enhance the thermal stability of HGBs, mechanical properties and water retention agents. Release the experimental results show that the swelling rate and the drug release rate of CS/SA-HGBs was three pH with the change regularity of change, so it has good pH response; the sustained release effects of the strength of the order: HTCC/SA-HGBs, BGCS/SA-HGBs, HTCC/SA-HGBs.

【學(xué)位授予單位】：華南農(nóng)業(yè)大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2016
【分類號】：O636.1;TQ460.4

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