抗結(jié)核病載藥支架的制備及其藥物釋放行為和成骨性能評(píng)價(jià)
發(fā)布時(shí)間：2018-11-14 20:29
【摘要】：骨結(jié)核病是由結(jié)核桿菌引起的一種肺外結(jié)核病,嚴(yán)重威脅著人們的健康。在重癥骨結(jié)核的治療中,一般采用骨清除術(shù)清除病灶,并在術(shù)后進(jìn)行骨修復(fù)治療和長(zhǎng)期多種藥物治療。病灶部位的藥物濃度決定著治療效果,然而全身高濃度的藥物也難以保證病灶部位達(dá)到有效藥物濃度,而長(zhǎng)期全身多種藥物治療會(huì)對(duì)患者的肝腎造成嚴(yán)重?fù)p傷,同時(shí)術(shù)后的骨缺損修復(fù)也存在供體不足、修復(fù)效果不佳等問(wèn)題。所以,亟需開(kāi)發(fā)一種能夠長(zhǎng)期緩釋多種藥物的局部給藥骨修復(fù)材料,不僅可以實(shí)現(xiàn)多種藥物的持續(xù)釋放,還可以促進(jìn)骨再生修復(fù)�；谝陨蠁�(wèn)題,本文旨在設(shè)計(jì)和制備可長(zhǎng)期緩釋多種藥物的聚內(nèi)酯載藥支架,并研究和評(píng)價(jià)其藥物釋放行為和骨修復(fù)性能。首先,為了滿足油溶性藥物的負(fù)載與長(zhǎng)效釋放,本文通過(guò)開(kāi)環(huán)聚合設(shè)計(jì)并制備了一種新型的聚內(nèi)酯——聚(己內(nèi)酯)-b-聚(丙交酯-co-乙交酯)(b-PLGC)三元嵌段共聚物,該聚合物與無(wú)規(guī)共聚物在熱力學(xué)性能、親疏水性、藥物釋放性能等方面有很大不同。本文將得到的b-PLGC與β-磷酸三鈣(β-TCP)通過(guò)共混載藥法復(fù)合,制備了負(fù)載油溶性利福平(RFP)的三維多孔支架,并通過(guò)掃描電鏡、熱重分析等測(cè)試分析了復(fù)合支架的形貌、孔結(jié)構(gòu)、TCP含量及力學(xué)性能;通過(guò)紫外-可見(jiàn)分光光度計(jì)測(cè)試分析了復(fù)合支架的載藥量、包封率及體外藥物釋放行為；通過(guò)體外細(xì)胞培養(yǎng)實(shí)驗(yàn)評(píng)價(jià)復(fù)合支架的細(xì)胞親和性;通過(guò)兔橈骨缺損部位的動(dòng)物實(shí)驗(yàn)評(píng)價(jià)支架的體內(nèi)藥物釋放行為及成骨性能。結(jié)果表明：復(fù)合支架可以實(shí)現(xiàn)RFP的持續(xù)84天的緩慢釋放,且體內(nèi)的局部藥物濃度高于全身血藥濃度。同時(shí),支架具有良好的細(xì)胞親和性和成骨性能,在重癥骨結(jié)核病的治療中有良好的應(yīng)用前景。其次,為了滿足水溶性藥物的負(fù)載與長(zhǎng)效釋放,本文通過(guò)水包油乳液法制備了負(fù)載水溶性異煙肼(INH)的TCP@明膠復(fù)合微球,并通過(guò)掃描電鏡、熱重分析等測(cè)試和分析了微球的形貌、TCP含量、藥物釋放行為,發(fā)現(xiàn)該微球可以實(shí)現(xiàn)INH的持續(xù)30天緩慢釋放。本文將載INH的微球與b-PLGC復(fù)合,制備了負(fù)載INH的微球/b-PLGC復(fù)合支架,并通過(guò)掃描電鏡、紫外-可見(jiàn)分光光度計(jì)等測(cè)試和分析微球／聚內(nèi)酯支架的形貌、TCP含量及藥物釋放行為。結(jié)果表明：本文成功地將INH通過(guò)TCP@明膠復(fù)合微球負(fù)載于支架中,大大地降低了INH的初期爆發(fā)釋放量,實(shí)現(xiàn)了INH從支架中長(zhǎng)達(dá)84天的可持續(xù)緩慢釋放。最后,本文將上述兩種方法結(jié)合成功地制備了同時(shí)負(fù)載INH和RFP的緩釋支架,該支架能夠同時(shí)實(shí)現(xiàn)兩種藥物持續(xù)84天的緩慢平穩(wěn)釋放,為重癥骨結(jié)核的長(zhǎng)期多種藥物治療提供了新方法。該支架不僅能負(fù)載以INH和RFP為代表的水溶性/油溶性抗結(jié)核藥物,也可以負(fù)載其他似溶解性的藥物,從而滿足其他需要多種藥物同時(shí)治療疾病的需求。
[Abstract]:Bone tuberculosis is a kind of extrapulmonary tuberculosis caused by Mycobacterium tuberculosis, which is a serious threat to people's health. In the treatment of severe bone tuberculosis, bone clearance is commonly used to clear the focus, and bone repair and long-term multi-drug therapy are performed after operation. The concentration of drugs in the lesion site determines the therapeutic effect. However, it is difficult to ensure the effective concentration of the drug in the focus area with high concentration of drugs throughout the body. However, long-term systemic drug therapy will cause serious damage to the liver and kidney of the patient. At the same time, the defect repair also has some problems, such as insufficient donor, poor repair effect and so on. Therefore, there is an urgent need to develop a local bone repair material that can release many drugs for a long time, which can not only realize the sustained release of many drugs, but also promote bone regeneration. In view of the above problems, the aim of this paper is to design and prepare poly (lactone) loaded stents that can release many kinds of drugs for a long time, and to study and evaluate their drug release behavior and bone repair performance. First, in order to satisfy the loading and long-term release of oil-soluble drugs, In this paper, a novel poly (caprolactone) -b (lactide co- glycolide) (b-PLGC) ternary block copolymer was designed and prepared by ring-opening polymerization. Hydrophobicity, drug release performance and other aspects are very different. In this paper, b-PLGC and 尾 -tricalcium phosphate (尾-TCP) were used to prepare the three-dimensional porous scaffolds loaded with oil-soluble rifampicin (RFP), and the scaffolds were prepared by scanning electron microscopy (SEM). The morphology, pore structure, TCP content and mechanical properties of the composite scaffold were analyzed by thermogravimetric analysis. The drug loading, encapsulation efficiency and drug release behavior of the composite scaffold were analyzed by UV-Vis spectrophotometer. The cell affinity of the composite scaffold was evaluated by cell culture in vitro and the drug release behavior and osteogenesis of the scaffold in vivo were evaluated by the animal experiment of rabbit radius defect. The results showed that the compound stent could release RFP slowly for 84 days, and the local drug concentration in vivo was higher than that in whole body. At the same time, the scaffold has good cell affinity and osteogenic properties, and has a good prospect in the treatment of severe bone tuberculosis. Secondly, in order to satisfy the loading and long-term release of water-soluble drugs, TCP@ gelatin composite microspheres loaded with water-soluble isoniazid (INH) were prepared by oil-in-water emulsion method. The morphology, TCP content and drug release behavior of the microspheres were measured and analyzed by thermogravimetric analysis. It was found that the microspheres could realize the slow release of INH for 30 days. In this paper, INH loaded microspheres and b-PLGC composite scaffolds were prepared, and the morphology of INH / b-PLGC composite scaffolds was measured and analyzed by scanning electron microscopy, UV-Vis spectrophotometer and so on. TCP content and drug release behavior. The results show that INH is successfully loaded into the scaffold through TCP@ gelatin composite microspheres, which greatly reduces the initial burst release of INH and realizes the sustained and slow release of INH from the scaffold for 84 days. Finally, the two methods were combined successfully to prepare the sustained release stents loaded with INH and RFP simultaneously. The stents could realize the slow and steady release of the two drugs for 84 days at the same time. It provides a new method for long-term multi-drug treatment of severe bone tuberculosis. The scaffold can not only load water-soluble / oil-soluble antituberculous drugs, such as INH and RFP, but also other dissolution-like drugs, so as to meet the need of other drugs to treat diseases simultaneously.
【學(xué)位授予單位】：北京化工大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2015
【分類號(hào)】：R318.08
本文編號(hào)：2332222
[Abstract]:Bone tuberculosis is a kind of extrapulmonary tuberculosis caused by Mycobacterium tuberculosis, which is a serious threat to people's health. In the treatment of severe bone tuberculosis, bone clearance is commonly used to clear the focus, and bone repair and long-term multi-drug therapy are performed after operation. The concentration of drugs in the lesion site determines the therapeutic effect. However, it is difficult to ensure the effective concentration of the drug in the focus area with high concentration of drugs throughout the body. However, long-term systemic drug therapy will cause serious damage to the liver and kidney of the patient. At the same time, the defect repair also has some problems, such as insufficient donor, poor repair effect and so on. Therefore, there is an urgent need to develop a local bone repair material that can release many drugs for a long time, which can not only realize the sustained release of many drugs, but also promote bone regeneration. In view of the above problems, the aim of this paper is to design and prepare poly (lactone) loaded stents that can release many kinds of drugs for a long time, and to study and evaluate their drug release behavior and bone repair performance. First, in order to satisfy the loading and long-term release of oil-soluble drugs, In this paper, a novel poly (caprolactone) -b (lactide co- glycolide) (b-PLGC) ternary block copolymer was designed and prepared by ring-opening polymerization. Hydrophobicity, drug release performance and other aspects are very different. In this paper, b-PLGC and 尾 -tricalcium phosphate (尾-TCP) were used to prepare the three-dimensional porous scaffolds loaded with oil-soluble rifampicin (RFP), and the scaffolds were prepared by scanning electron microscopy (SEM). The morphology, pore structure, TCP content and mechanical properties of the composite scaffold were analyzed by thermogravimetric analysis. The drug loading, encapsulation efficiency and drug release behavior of the composite scaffold were analyzed by UV-Vis spectrophotometer. The cell affinity of the composite scaffold was evaluated by cell culture in vitro and the drug release behavior and osteogenesis of the scaffold in vivo were evaluated by the animal experiment of rabbit radius defect. The results showed that the compound stent could release RFP slowly for 84 days, and the local drug concentration in vivo was higher than that in whole body. At the same time, the scaffold has good cell affinity and osteogenic properties, and has a good prospect in the treatment of severe bone tuberculosis. Secondly, in order to satisfy the loading and long-term release of water-soluble drugs, TCP@ gelatin composite microspheres loaded with water-soluble isoniazid (INH) were prepared by oil-in-water emulsion method. The morphology, TCP content and drug release behavior of the microspheres were measured and analyzed by thermogravimetric analysis. It was found that the microspheres could realize the slow release of INH for 30 days. In this paper, INH loaded microspheres and b-PLGC composite scaffolds were prepared, and the morphology of INH / b-PLGC composite scaffolds was measured and analyzed by scanning electron microscopy, UV-Vis spectrophotometer and so on. TCP content and drug release behavior. The results show that INH is successfully loaded into the scaffold through TCP@ gelatin composite microspheres, which greatly reduces the initial burst release of INH and realizes the sustained and slow release of INH from the scaffold for 84 days. Finally, the two methods were combined successfully to prepare the sustained release stents loaded with INH and RFP simultaneously. The stents could realize the slow and steady release of the two drugs for 84 days at the same time. It provides a new method for long-term multi-drug treatment of severe bone tuberculosis. The scaffold can not only load water-soluble / oil-soluble antituberculous drugs, such as INH and RFP, but also other dissolution-like drugs, so as to meet the need of other drugs to treat diseases simultaneously.
【學(xué)位授予單位】：北京化工大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2015
【分類號(hào)】：R318.08
【共引文獻(xiàn)】
相關(guān)期刊論文 前4條
1 張會(huì)軍;朱昌生;;脊柱結(jié)核手術(shù)入路的研究現(xiàn)狀[J];長(zhǎng)治醫(yī)學(xué)院學(xué)報(bào);2013年04期
2 周樹(shù)根;陳少慧;溫干軍;;脊柱結(jié)核前后路不同術(shù)式的選擇及療效分析[J];中國(guó)醫(yī)藥科學(xué);2014年05期
3 丁文斌;徐偉力;關(guān)煉雄;黃江鴻;王大平;;α-氰基丙烯酸丁酯類醫(yī)用骨膠改性研究進(jìn)展[J];國(guó)際骨科學(xué)雜志;2014年06期
4 桂雪洋;鄭欣;陳一心;;可降解抗生素緩釋系統(tǒng)的應(yīng)用進(jìn)展[J];中國(guó)骨與關(guān)節(jié)損傷雜志;2015年08期
相關(guān)博士學(xué)位論文 前1條
1 劉雨;裝載促血管再生基因的絲素支架構(gòu)建及其對(duì)真皮再生的影響[D];蘇州大學(xué);2015年
相關(guān)碩士學(xué)位論文 前4條
1 陳建美;明膠/氧化海藻酸鈉交聯(lián)纖維載抗生素用于燙傷修復(fù)的研究[D];西南交通大學(xué);2014年
2 李趙波;靜電紡絲素蛋白/BAMG搭載VEGF構(gòu)建復(fù)合組織工程支架[D];東華大學(xué);2014年
3 熊思;絲素蛋白的降解性能及其三維打印生物活性支架在皮膚修復(fù)中的應(yīng)用研究[D];浙江大學(xué);2015年
4 蔡虹霞;復(fù)合基質(zhì)細(xì)胞衍生因子-1α的絲素—細(xì)菌纖維素膜促進(jìn)大鼠子宮損傷的再生修復(fù)研究[D];浙江大學(xué);2015年
，本文編號(hào)：2332222
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