發(fā)布時(shí)間：2018-01-03 06:04

  本文關(guān)鍵詞：載銀二氧化鈦抗菌涂層氣管插管導(dǎo)管的研制和基礎(chǔ)研究　出處：《浙江中醫(yī)藥大學(xué)》2014年博士論文　論文類型：學(xué)位論文

  更多相關(guān)文章： 氣管插管導(dǎo)管 抗菌涂層 載銀二氧化鈦 表征 抗菌性能 不良反應(yīng)

【摘要】：目的研發(fā)一種能預(yù)防氣管插管機(jī)械通氣引發(fā)的呼吸機(jī)相關(guān)性肺炎的氣管插管導(dǎo)管。 方法以醫(yī)用聚乙烯氣管插管導(dǎo)管為基材、載銀二氧化鈦為抗菌劑、TEOS為硅源、KH570和MTES為有機(jī)相前驅(qū)體,通過溶膠-凝膠法制備TEOS/KH570/MTES/Ag-TiO2抗菌有機(jī)硅溶膠,將聚乙烯氣管插管導(dǎo)管表面活化處理,通過浸漬涂布法制備TEOS/KH570/MTES/Ag-TiO2抗菌涂層氣管插管導(dǎo)管。進(jìn)而研究分析抗菌涂層的表征：通過溶膠穩(wěn)定性測(cè)試、涂層硬度和附著力測(cè)試、涂層紅外光譜分析、涂層表面形貌分析、涂層透光性檢測(cè)和ICP-MS測(cè)試,以確定載銀二氧化鈦抗菌涂層的成分配比；選取標(biāo)準(zhǔn)銅綠假單胞菌、大腸埃希菌、金黃色葡萄球菌作為實(shí)驗(yàn)觀察菌株,通過浸漬菌液培養(yǎng)法檢測(cè)涂層導(dǎo)管抗菌性能；通過口腔黏膜刺激試驗(yàn)、熱原檢查、溶血試驗(yàn)、急性全身毒性試驗(yàn)和體外細(xì)胞毒性試驗(yàn),以明確其是否存在生物不良反應(yīng),確定抗菌涂層導(dǎo)管的生物相容性和生物安全性。 結(jié)果TEOS/KH570/MTES/Ag-TiO2=15/6/1/≤1.0抗菌溶膠在聚乙烯氣管插管導(dǎo)管表面附著力(0級(jí))、表面硬度(5H)、溶膠穩(wěn)定不沉淀,說明抗菌溶膠涂層與聚乙烯氣管插管導(dǎo)管表面緊密附著,既保證了導(dǎo)管的柔韌性,又保證涂層在壓折后不易斷裂,而且溶膠涂層均勻穩(wěn)定；涂層紅外光譜分析顯示TEOS/KH570/MTES/Ag-TiO2(15/6/1/1.0)抗菌溶膠交聯(lián)結(jié)合穩(wěn)定,保證涂層成分形成一體,不易掉落；涂層表面形貌分析顯示涂層表面非常均勻平整,無小顆粒和相分離現(xiàn)象,涂層表面網(wǎng)絡(luò)結(jié)構(gòu)致密,穩(wěn)定無分離,保證了涂層導(dǎo)管的光滑；涂層透光性檢測(cè)顯示平均透過率90%,且具有增透效果；ICP-MS測(cè)試,銀離子析出幾乎可以忽略不計(jì),說明抗菌涂層管具有良好的抗菌性能和穩(wěn)定性�？咕囼�(yàn)顯示載銀二氧化鈦抗菌涂層氣管插管導(dǎo)管具有明確的抗菌作用,能殺滅銅綠假單胞菌、金黃色葡萄球菌、大腸埃希菌,在不同的抗菌劑濃度時(shí)殺菌強(qiáng)度不同�？咕繉託夤懿骞軐�(dǎo)管涂層載銀二氧化鈦含量越高,則抗菌性能越強(qiáng),達(dá)到1%濃度后,則處于飽和殺菌狀態(tài),可幾乎完全殺滅所有細(xì)菌,說明1%載銀二氧化鈦抗菌涂層氣管插管導(dǎo)管是有效抗菌的最低濃度。口腔黏膜刺激試驗(yàn)顯示1%載銀二氧化鈦抗菌涂層氣管插管導(dǎo)管浸提液對(duì)金黃地鼠口腔粘膜未出現(xiàn)刺激反應(yīng)；熱原檢查顯示涂層管浸提液3h內(nèi)的最高升溫分別為0℃,0℃,0.03℃,總升溫為0.03℃；溶血試驗(yàn)顯示涂層管的吸光度分別為：0.016、0.014、0.021,平均值為0.0170,計(jì)算得溶血率為0.7512%；急性全身毒性試驗(yàn)顯示涂層管浸提液在整個(gè)試驗(yàn)過程均無動(dòng)物死亡,且未見異常反應(yīng),體外細(xì)胞毒性試驗(yàn)細(xì)胞形態(tài)正常,貼壁生長(zhǎng)良好,胞漿內(nèi)有離散顆粒,無細(xì)胞溶解,評(píng)為無毒,判定分級(jí)為0級(jí),相對(duì)細(xì)胞增殖率均大于100%。 結(jié)論以TEOS/KH570/MTES/Ag-Ti02=15/6/1≤1.0比例和1%濃度載銀二氧化鈦抗菌劑制備的抗菌涂層氣管插管導(dǎo)管表征優(yōu)良,抗菌性能優(yōu)越,滿意的生物相容性和安全性,可以作為預(yù)防VAP的臨床前試驗(yàn)候選導(dǎo)管。
[Abstract]:Objective to develop a tracheal intubation catheter that can prevent ventilator-associated pneumonia caused by endotracheal intubation.
Methods medical polyethylene endotracheal intubation catheter as the substrate, silver loaded titanium dioxide as antibacterial agent, TEOS as silicon source, KH570 and MTES as organic precursor, prepared by sol-gel method TEOS/KH570/MTES/Ag-TiO2 antibacterial silicone sol, polyethylene endotracheal tube surface activation, by dip coating prepared by TEOS/KH570/MTES/Ag-TiO2 antibacterial coating the endotracheal tube. Further characterization of the antibacterial coating by sol stability test, hardness test and adhesion test, infrared spectrum analysis analysis of coating, coating surface morphology, coating light detection and the ICP-MS test to determine the composition of silver doped titania antibacterial coating; the criteria for the selection of Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus as observed by dipping strains, bacterial liquid antibacterial properties were detected through buccal adhesive coating catheter; Membrane stimulation test, pyrogen test, hemolysis test, acute systemic toxicity test and in vitro cytotoxicity test were performed to determine whether there were any adverse reactions and determine the biocompatibility and biosafety of the antibacterial coating catheter.
The results of TEOS/KH570/MTES/Ag-TiO2=15/6/1/ is less than or equal to 1 antimicrobial sol in polyethylene endotracheal tube surface adhesion (0), surface hardness (5H), stable sol precipitation, antifungal sol coating and polyethylene tightly attached to the endotracheal tube surface, both to ensure the catheter flexibility, and ensure that the coating is not easy to break in the fold, and the sol coating uniformity stable coating; infrared spectrum analysis showed that TEOS/KH570/MTES/Ag-TiO2 (15/6/1/1.0) antibacterial sol cross-linking and stability, to ensure the coating composition to form a whole, not easy to fall off; the coating surface morphology analysis showed that the coating surface is very smooth, small particles and phase separation, surface coating compact network structure, stable without separation, to ensure the smooth coating catheter; coating light transmission detection showed an average transmittance of 90%, and has the antireflection effect; ICP-MS test, silver ion release almost Negligible, that antibacterial coating tube has antibacterial properties and good stability. The antibacterial test showed that the TiO2 Ag antibacterial coating the endotracheal tube with a clear antibacterial effect, can kill Pseudomonas aeruginosa, Staphylococcus aureus, Escherichia coli, antibacterial agent in different concentration. Different intensity of sterilization antimicrobial coated endotracheal tube coating the TiO2 Ag content is higher, is stronger antibacterial properties, the concentration reached 1% after sterilization are in saturated state, can almost completely kill all bacteria, 1% Ag / TiO2 antibacterial coated endotracheal tube is the lowest concentration of effective antibiotic. Oral mucosa irritation test showed that 1% Ag / TiO2 antimicrobial coated endotracheal tube extract on hamster oral mucosa without stimulation reaction; pyrogen test showed that the highest temperature liquid extraction tube coating 3H were 0 DEG c, 0 C, 0.03 C, the total temperature is 0.03 DEG C; hemolysis test showed absorbance of coated pipe is 0.016,0.014,0.021, the average value of 0.0170, calculated the hemolysis rate was 0.7512%; acute toxicity test showed that coating tube extracts had no animal died in the whole test process, and no abnormal reaction, morphology and cytotoxicity in vitro the test of normal cell, adherent growth is good, in the cytoplasm of discrete particles, no cell lysis, as non-toxic, determination of grade 0, the relative cell proliferation rates were greater than 100%.
Conclusion the TEOS/KH570/MTES/Ag-Ti02=15/6/1 is less than or equal to 1 and 1% concentration ratio of Ag / TiO2 antibacterial coating characterization of endotracheal tube the preparation of excellent, excellent antibacterial properties, biocompatibility and biological safety can be satisfied, pre clinical trials for prevention of VAP catheter as candidate.

【學(xué)位授予單位】：浙江中醫(yī)藥大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2014
【分類號(hào)】：R563.1

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