本文選題：磷酸膽堿　切入點：仿生　出處：《浙江大學(xué)》2005年博士論文

【摘要】：本論文針對生物材料的生物相容性這一關(guān)鍵科學(xué)問題,依據(jù)現(xiàn)代仿生學(xué)原理,以磷酸膽堿生物膜仿生為手段,分別開展了介入醫(yī)用裝置表面和納米藥物微載體界面的高生物相容性設(shè)計與研究: 以均勻穩(wěn)定的、高血液相容性的藥物控釋介入支架為目標(biāo),采用由細(xì)胞膜仿生單體甲基丙烯酸磷酸膽堿酯(MPC)、疏水單體甲基丙烯酸十八酯(SMA)以及交聯(lián)單體甲基丙烯酸羥丙酯(HPMA)和甲基丙烯酸三甲氧基硅丙酯(TSMA)四元復(fù)合,成功地制備了一種可交聯(lián)磷酸膽堿細(xì)胞膜仿生醫(yī)用涂層材料。采用浸涂(Dip-Coating)和熱交聯(lián)技術(shù),利用此仿生材料獲得了仿生涂層和帶藥仿生涂層。原子力顯微鏡、接觸角和紫外光譜的測試結(jié)果表明,仿生涂層具有良好的穩(wěn)定性;接觸角測試的結(jié)果顯示,當(dāng)仿生涂層從空氣環(huán)境變?yōu)樗h(huán)境后,涂層的表面會經(jīng)歷一個表面自遷移重組的過程,最終獲得了一個在水環(huán)境下,細(xì)胞膜仿生磷酸膽堿富集的仿生涂層表面。復(fù)鈣化時間測試和血小板粘附實驗表明,仿生涂層的引入能夠顯著提高材料的血液相容性。以Rhodamine S為模型藥物,對仿生涂層的藥物緩釋行為進(jìn)行的初步探索所得結(jié)果表明,藥物的釋放行為可以通過仿生涂層中的交聯(lián)劑的含量進(jìn)行有效的調(diào)節(jié)。穩(wěn)定的、高血液相容性的藥物涂層材料為帶藥支架設(shè)計提供了良好的物質(zhì)基礎(chǔ)。 進(jìn)一步復(fù)合和優(yōu)化了浸涂、吹管和熱交聯(lián)技術(shù),在具有復(fù)雜體型結(jié)構(gòu)的冠脈支架表面獲得了均勻的、穩(wěn)定的、可長期釋放雷帕霉素藥物的仿生藥物涂層。光學(xué)顯微鏡和激光共聚焦顯微鏡(CLSM)測試表明,(載藥)仿生涂層能夠被光滑、均勻的涂覆于支架表面;(載藥)涂層在支架球囊擴(kuò)張過程中不脫落、不開裂、具有良好的穩(wěn)定性。雷帕霉素藥物涂層的體外釋放實驗結(jié)果表明,冠脈支架的雷帕霉素藥物涂層可維持長期、穩(wěn)定、有效的藥物釋放。體外實驗表明,仿生涂層可有效降低支架表面的血小板粘附。小動物(兔)和大動物(小型豬)實驗結(jié)果均表明,這種均勻的、穩(wěn)定的、高血液相容性的仿細(xì)胞膜載藥涂層可長效釋放雷帕霉素,有效降低再狹窄,為國產(chǎn)藥物支架的產(chǎn)業(yè)化生產(chǎn)提供了有效的技術(shù)支撐。 以具有優(yōu)異的血液相容性和高穩(wěn)定性的納米藥物載體為目標(biāo),本文通過MPC的原子轉(zhuǎn)移自由基聚合(ATRP),得到了細(xì)胞膜仿生的兩親性分子CMPC。將
[Abstract]:Aiming at the key scientific problem of biocompatibility of biomaterials, according to the principle of modern bionics, the bionic method of choline phosphate biofilm is used in this paper. The design and study of high biocompatibility between the surface of interventional medical device and the interface of nano-drug microcarrier were carried out. The goal is a uniform, stable, highly compatible drug controlled release interventional stent. The composite was composed of the cell membrane bionic monomer choline methacrylate (MPC), the hydrophobic monomer octadecyl methacrylate (SMA) and the crosslinking monomer (hydroxypropyl methacrylate) and the trimethoxypropyl methacrylate (TSMA). A biomimetic medical coating material of crosslinked choline phosphate membrane was successfully prepared. The bionic coating and bionic coating with medicine were obtained by dip-Coatingand thermal crosslinking technology. Atomic force microscope (AFM) was used to prepare the biomimetic coating. The results of contact angle and UV spectra show that the bionic coating has good stability, and the contact angle test shows that when the bionic coating changes from air to water, The surface of the coating will undergo a process of surface self-migration and recombination. Finally, a bionic coating surface with membrane bionic choline phosphate enrichment in water environment is obtained. The multiple calcification time test and platelet adhesion test show that, The introduction of bionic coating can significantly improve the blood compatibility of the material. The preliminary study on the drug release behavior of the biomimetic coating using Rhodamine S as model drug shows that, The drug release behavior can be effectively regulated by the content of cross-linking agent in the bionic coating. The stable and high blood compatibility drug coating materials provide a good material basis for the design of drug-bearing scaffolds. Further recombination and optimization of dipping, blowing tube and thermal crosslinking techniques to obtain uniform and stable coronary stents with complex structures, Biomimetic coatings that release rapamycin over a long period of time. Optical and laser confocal microscopy (CLSM) tests show that the bionic coating can be smooth. The uniform coating on the surface of the stent does not fall off, does not crack, and has good stability during the balloon dilation of the stent. The results of in vitro release of rapamycin drug coating show that, Rapamycin drug coating on coronary stent can maintain long-term, stable and effective drug release. Bionic coating can effectively reduce platelet adhesion on the scaffold surface. The experimental results of small animals (rabbits) and large animals (small pigs) show that this kind of uniform, stable, The coating with high blood compatibility can release rapamycin for a long time and reduce restenosis effectively. It provides an effective technical support for the industrial production of domestic drug stents. Aiming at the excellent blood compatibility and high stability of nanopharmaceutical carriers, a biomimetic amphiphilic molecule of MPC was obtained by atom transfer radical polymerization of MPC.
【學(xué)位授予單位】：浙江大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2005
【分類號】：R314

【引證文獻(xiàn)】

相關(guān)碩士學(xué)位論文 前2條

1 俞洪飛;醫(yī)用滌綸材料表面磷酸膽堿仿生改性及其抗凝血性能研究[D];西南交通大學(xué);2011年

2 張靜;仿細(xì)胞膜結(jié)構(gòu)聚合物交聯(lián)納米膠束的構(gòu)建及其應(yīng)用研究[D];西北大學(xué);2010年

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本文編號：1687197