复方邻苯二甲醛纳米乳的研制
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摘要
本研究以纳米乳为载体,将邻苯二甲醛和癸甲溴铵两种消毒剂成分进行复配,旨在开发一种高效、安全、稳定的复合消毒剂,用于环境消毒。在建立分析方法、筛选处方的基础上制备出复方邻苯二甲醛纳米乳,并对其理化性质、安全性和杀菌性能进行了较为系统的研究。
     试验一:复方邻苯二甲醛纳米乳分析方法的建立。以邻苯二甲醛为复方邻苯二甲醛纳米乳测定的指标性成分,通过紫外分光光度法测定邻苯二甲醛的含量。建立复方邻苯二甲醛纳米乳的紫外分析方法,并对其回收率、精密度等进行研究。结果表明,以265nm作为紫外检测波长,得到的标准曲线方程为:A=0.0078C-0.0126(r=0.9998),该方程在20~100μg/mL浓度范围内,线性关系良好,平均回收率为99.16%,回收率的相对标准偏差(RSD)为0.75%、进样重复性的RSD为0.68%、日内精密度和日间精密度的RSD均小于1%。本研究建立的分析方法回收率高、精密度和重复性良好,可满足其质量控制研究。
     试验二:复方邻苯二甲醛纳米乳的制备。利用纳米乳的评价标准,初步筛选纳米乳处方,同时利用伪三元相图对纳米乳形成的影响因素进行考察,筛选出复方邻苯二甲醛纳米乳的最佳处方是:表面活性剂为癸甲溴铵,助表面活性剂为1,2-丙二醇,油相为IPM,表面活性剂与助表面活性剂比例(Km)为4:1,混合表面活性剂与油相比例为9:1,同时加入0.05%的离子螯合剂。本研究筛选的复方邻苯二甲醛纳米乳的制备方法简单,易于操作。
     试验三:复方邻苯二甲醛纳米乳的质量及稳定性评价。利用透射电镜、激光粒度分析仪对其形态和粒径进行检测;通过染色法确定纳米乳类型;通过紫外分光光度法测定邻苯二甲醛的含量;通过离心、加速试验对其稳定性进行评价。制备的复方邻苯二甲醛纳米乳为澄清透明液体,为水包油型纳米乳;在透射电镜下呈球形、粒径分布均匀,平均粒径48.2nm;邻苯二甲醛含量为:87.26mg·mL~(-1);离心和恒温加速试验显示其质量稳定。
     试验四:复方邻苯二甲醛纳米乳的杀菌性能研究。通过悬液定量杀菌试验考察不同浓度的复方邻苯二甲醛纳米乳的杀菌能力,同时考察了PH值以及有机干扰物对杀菌效能的影响。结果表明:在PH为7.2条件下含OPA 50mg/L的复方邻苯二甲醛纳米乳消毒液作用1min即可杀灭大肠杆菌和金黄色葡萄球菌(杀灭对数值>5):碱性条件有利于杀菌作用的发挥;有机干扰物对杀菌作用有一定影响。
     试验五:复方邻苯二甲醛纳米乳的安全性与金属腐蚀性研究。通过急性毒性、皮肤和眼部刺激试验对复方邻苯二甲醛纳米乳的安全性进行评价,同时研究该纳米乳消毒剂对金属的腐蚀性。结果表明,复方邻苯二甲醛纳米乳对小鼠的LD_(50)>5000mg/kg.bw,属于无毒级;对家兔皮肤和眼部均无刺激,对铜和不锈钢基本无腐蚀:对碳钢和铝有轻度腐蚀。本研究制备的复方邻苯二甲醛纳米乳安全性良好,对金属腐蚀性低。
     试验六:复方邻苯二甲醛纳米乳的消毒模拟现场试验。结果显示:含邻苯二甲醛50mg/L的复方邻苯二甲醛纳米乳消毒剂可有效杀灭环境中99.96%的细菌。此浓度的消毒剂消毒效果良好,能满足现场消毒的需要。
In this research,two disinfectant ingredients OPA and DDAB were made duplicate matches by using nanoemulsion as a new carrier.It was purposed to develop a new effective, safe and stable disinfectant for surrounding sterization.Compound OPA nanoemulsion was prepared on the base of establishment of analytical method,screening of nanoemulsion prescription and so on.Physics and chemistry nature,security and germicidal efficentcies were systemically studied.
     Part 1:The establishment of analytical method of compound OPA nanoemulsion.OPA was determined as content of compound OPA nanoemulsion.Establishing the Ultraviolet analytical methed of compound OPA nanoemulsion to study the recovery rate and accuracy. Results showed that OPA has the maximal absorption in 265nm.The standard curve was A=0.0078C—0.0126(r=0.9998).The good linear range was 20~100μg/mL.The average recovery rate was 99.16%.RSD of the recovery rate and repeatability were 0.75%and 0.68%. The inter-day and intra-day precision of determination of matrin is less than 1%.The analytical method in this study has high recovery,good accuracy and repeatability,which can satisfy quality control research.
     Part 2:The preparation of compound OPA nanoemulsion.Prescriptions of nanoemulsion were filtrated by the nanoemulsion evaluation standard.The influence factors of forming nanoemulsion were also investigated by pseudoternary phase diagrams.Results showed that the best prescriptions of the nanoemulsion were:the surfactant,cosurfactant and the oil phase were DDAB,1,2-Propylene glycol and IPM,respectively;The ratio of surfactant to cosurfactant was 4:1 and the mixed surfactant to oil was 9:1;0.05%EDTA was added.The preparation method of compound OPA nanoemulsion was simple and easy to manipulate.
     Part 3:The evaluation of stability and quality of compound OPA nanoemulsion.The appearance and diameter was detected by Transmission Electron Microscope(TEM) and Zetasizer Nano ZS testing.The content of OPA in nanoemulsion was tested by ultraviolet analytical methed.The stability was evaluated by centrifuging and acceleration experiments. The results showed that the compound OPA nanoemulsion was clarified and transparent liquid.Its type was O/W.Its average diameter was 48.2 nm and the content of OPA in nanoemulsion was 87.26 mg·mL~(-1).The quality of compound OPA nanoemulsion was stable.
     Part 4:Study on the germicidal efficacy of compound OPA nanoemulsion.The suspension test was conducted to learn efficacies of OPA nanoemulion in different concentration. Tests of PH and organic influential factor were also conducted.Results showed that when 50mg/L OPA in the compound OPA nanoemulsion had been for 1 minute at PH value of 7.2,The logarithm mean reduction was more the 5 against E.coli and S.aureus.The alkaline OPA nanoemulion is better for disinfection,organic substance influences its efficacy.
     Part 5:The safety evaluation and corrosive effect of compound OPA nanoemulsion.Safety of compound OPA nanoemulsion was evaluated by acute toxicity,skin irritation and eye irritation.It showed that the accumulation LD_(50) of the compound OPA nanoemulsion test on mice was more than 5000mg/kg.bw.The stimulation to the skin and eye of domestic rabbits were all nontoxic.It was not corrosive to copper and stainless steel,slight corrosive to carbon and aluminum.The compound OPA nanoemulsion is actually nontoxic and light corrosive and can be used for disinfection.
     Part 6:The disinfection simulated field test of compound OPA nanoemulion.Results showed that compound OPA nanoemulsion containing 50mg/L OPA can kill 99.96% bacterials in the environment.This concentration of the disinfectant had good disinfectant efficency which can satisfy our use.
引文
[1]沈建忠.兽医药理学[M].北京:中国农业出版社,2002.
    [2]张文福.医学消毒学[M].北京:军事医学科学出版社,2002.
    [3]俞树荣.微生物学和微生物学检验[M].北京:人民卫生出版社,1999.
    [4]薛广波.现代消毒学[M].北京:人民军医出版社,2002.
    [5]李崇珍.内窥镜灭菌技术进展[J].2004,18(10):1799-1801.
    [6]蔡宝祥.家畜传染病学[M].中国农业出版社,2005.
    [7]刘子鑫.消毒及消毒剂简介[J].中国兽医杂志,2004,40(7):37-38.
    [8]沈建中.化学消毒剂组成复方协同杀菌作用研究进展[J].医学动物防治.2004,20(10):596-599.
    [9]魏秋华.抗菌剂的研究进展[J].中国消毒学杂志,2003,20(1):30.
    [10]薛文青.季铵盐阳离子表面活性消毒剂研究进展[J].中华医院感染学杂志,2002,12(8):634.
    [11]陆婉英,黄青山,励俊.生物消毒剂的研究进展[J].中国消毒学杂志,2003,20(3):231.
    [12]常青春.季铵盐表面活性剂的发展及应用[J].佳木斯大学学报(自然科学版),2003,2(1):503-506.
    [13]陈拥军,李本高.有机抗菌剂研究的新进展[J].石油炼制与化工,1997,28(1):32-35.
    [14]薛广波.季铵盐类消毒剂[M].北京:人民卫生出版社,1993.
    [15]郭振东.季铵盐类消毒剂[M].北京:人民军医出版社,2006.
    [16]张文福.医学消毒学[M].北京:军事医学科学出版社,2005.
    [17]李六亿.一种新的化学消毒剂—邻苯二甲醛[J].北京:中华医院感染学杂志,2003,13(4):397-398.
    [18]LennartJ,Walter BS.Determine by new fluorescent O-phthalaldehyde Stain.J Histochem Cytochem,1996,14(7):525.
    [19]Streck Sabach Sc,et al.Perioral Stains after Ortho-Phthalaloehyde Disinfection of EchoProbes.[J].Anesth analg,2003,99(4):1032.
    [20]Viktor Majtan,Lubica Majtanova.The effect of new disinfectant substances on the metabolism of Enterobacter cloacae[J].International Journal of Antimicrobial Agents,1999,11(2):59.64.
    [21]Alfa Mj,Sitter DL.Inhospital evaluation of orthophthalaidehyde as a high level disinfectant for flexible endoscopes[J].J Hosp Infect,1994,26(1):15-26.
    [22]Walsh S E,Maillard J Y,Russell A D.Ortho-phthalaldehyde:a possible alternative to glutaraldehyde for high level disinfection[J].Appl microbiology,1999,86(6):1039-1046.
    [23]Fraud S,Maillard JY,Russell AD.Comparison of the mycobactericidal activity of ortho-phtha laldehyde,glutarldehydde by a quantitative suspension test.Hosp Infect,2001,48(3):2114-221.
    [24]Walsh S E,Maillard J Y,Simons C,et al.Studies on the mechanisms of the antibacterial action of ortho-phthalaldehyde[J].Appl Microbiology,1999,87(5):702-710.
    [25]陈菁,许能峰.邻苯二甲醛消毒作用及其机制[J].国外医学·流行病学传染病学分册,2004,31(2):121-124.
    [26]常文军,蔡全才,徐荷,等.邻苯二甲醛消毒剂研究进展[J].中国消毒学杂志,2004,21(1):67-69.
    [27]沈伟.消毒剂百毒杀性能的实验室研究[J].中国消毒学杂志,2005,9(3):185-161.
    [28]马贤坤,车娟娟,阳艳林.癸甲溴铵溶液消毒性能的试验观察[J].试验研究,2007,6(1):9-10.
    [29]马新爱,刘吉起.复方季铵盐消毒剂部分性能实验观察[J].中国消毒学杂志,2005,22(2):187-189.
    [30]王莉.复合季铵盐消毒剂杀菌效果的实验观察[J].中国消毒学杂志,2005,17(1):31-33.
    [31]孙祖越,王丽君.双链季铵盐消毒效果及安全性评价[J].湖北预防医学杂,2001,12(2):1-2.
    [32]孟林,周丽萍.双季铵盐杀菌剂的合成及其杀菌性能的研究[J].化学工程师,2005,13(4):59-60.
    [33]T.P.Hoar and J.H.Schulman,Nature,152:102.
    [34]李干佐,郭荣等.微乳液理论及其应用[M].北京:石油化工出版社,1995.
    [35]崔正刚,殷福珊.微乳化技术及应用[M].北京:中国轻工业出版者,2001.
    [36]杨锦宗,兰云军.微乳状液制备技术及其发展状况[J].精细化工,1995,12(4):7.
    [37]Schwuger M J,Stickdom K,Schomcker R.Microemulsions intechnical processes[J].Chem Rev,1995,95(4):849.
    [38]陈华兵,翁婷,杨祥良,等.微乳在现代药剂学中的研究进展[J].中国医药工业杂志.2004,35(8):502.
    [39]张莉,向东,洪诤,等.肝靶向去甲斑蝥素微乳的研究[J].药学学报,2004.39(8):650-655.
    [40]陈华兵,翁婷,杨祥良,等.微乳在现代药剂学中的研究进展.中国医药工业杂志[J].2004,35(8):502.
    [41]张阳德.纳米药物学[M].北京:化学工业出版社,2006.
    [42]曹发昊.苦参碱微乳的研究[D].西北农林科技大学硕士论文,2007.
    [43]孙红武.黄连素纳米乳给药系统的研究[D].西北农林科技大学硕士论文,2007.
    [44]李干佐,刘尚营,徐桂英,等.阳离子表面活性剂中相微乳液的形成和特性(Ⅱ)[J].日用化学工业,1995,9:65-68.
    [45]滕弘霓,滕人为,陈宗淇.醇的链长对微乳状液形成的影响[J].化学研究与应用,1997,9(4):420-424.
    [46]C.S.Chem,C.W.Liu.Effect of short-chain alcohols on the oil-in-water microemulsion polymerization of styrene[J].Colloid polym Sci.2000,278.329-336.
    [47]寇贺红.丁香酚纳米乳的研制[D].西北农林科技大学硕士论文,2006.
    [48]Prince L M.Microemulsion:Theory and Practice[M].New York:Academic Press,1997.
    [49]汪杨,吴伟,阙俐.油-吐温-醇-水体系伪三元相图在自微乳化制剂研究中的应用[J].中国医药工业杂志,2005,36(6):345-348.
    [50]陆彬,张正全.用三角相图法研究药用微乳的形成条件[J].药学学报,2001,36(1):58-62.
    [51]王倩,丁红梅,周海源.微乳相图及工艺研究[J].西北药学杂志,1997,12(2):72.
    [52]张阳德.纳米药物学[M].北京:化学工业出版社,2006,118-145.
    [53]田佩瑶,李沽,魏建荣,等.紫外分光光度法快速测定消毒剂邻苯二甲醛[J].中国消毒学杂志,2004,21(4):316.
    [54]车宜平,丁晓静,赵珊,等.反相高效液相色谱法快速测定复方化学消毒剂中邻苯二甲醛[J].中国消毒学杂志2006,23(3):215-217.
    [55]朱广华,胡永桢,郑洪,等.L-谷氨酸分光光度法快速测定消毒剂中的邻苯二甲醛[J].中国消毒学杂志,2005 2(2):187-189.
    [56]马玉樊,卢婷利,陈涛,等紫外分光光度法测定O/W型青蒿素脂肪乳剂中青蒿素的含量[J].分析试验室,2007,12(26):184-185.
    [57]田佩瑶,李洁,魏建荣,等.紫外分光光度法快速测定消毒剂邻苯二甲醛[J].中国消毒学杂志,2005,21(4):316.
    [58]芮亚培.红霉素纳米乳制备及药效学研究[D].西北农林科技大学硕士论文,2007.
    [59]张阳德.纳米药物学[M].北京:化学工业出版社,2006.
    [60]Radomska A,Dokruchi R.The use of the ingredients for microemuision preparation containing retinal and its esters[J].J Pharm,2000,196(2):131-134.
    [61]叶海英,张忠义,高中,等.法莫替丁微乳的研制及其质量评价[J].第一军医大学学 报,2003,23(1):68-70.
    [62]杨宝平,欧阳五庆.白藜芦醇纳米乳的制备及其质量评价[J].西北农业学报,2008,17(2):20-23.
    [63]王玉强.槲皮素微乳的研究[D].山东:山东大学,2006.
    [64]吴旭锦,欧阳五庆.黄芩甙纳米乳的制备[J].精细化工,2007,24(5):470-472.
    [65]王晓黎,蒋雪涛,刘皋林,等.环孢素A微乳口服液的制备及稳定性研究[J].中国现代应用药学杂志,2004,21(2):40-43.
    [66]C.S.Chem,C.W.Liu.Effect of short-chain alcohols on the oil-in-water microemulsion polymerization of styrene[J].Colloid polym Sci.2000,278.329-336.
    [67]M Jayne,Lawrence GDR.Mieroemulsion-based media as novel drug delivery systems[J].Advanced Drug Delivery Reviews,2000,45:89.
    [68]朱晓亮,陈志良,李国锋,等.利多卡因微乳的制备及电镜观察[J].南方医科大学学报,2006,26(4):515-525.
    [69]张柯萍,蔺胜照,陈国广,等.鸦胆子油微乳的制备及稳定性研究[J].华西药学杂志,2005,(20)3:199-201.
    [70]中国药典委员会编写.中国药典[M].北京:2005.
    [71]阳卫超.丁香酚纳米乳的研究[D].陕西:西北农林科技大学,2007.
    [72]卫生部卫生法制与监督司.消毒技术规范(2002版)[S].北京:中华人民共和国卫生部,2002.
    [73]Robison RA,Robinson DF,Ploeger BJ,et al.Clinical and laboratory efficacy tests of a new disinfectant[J].DentRes,1991,70:438.
    [74]薛文青,薛广波.杀菌牙膏的杀菌效果观察[J].现代预防医学,2005,22(2):544-545.
    [75]孟庆增,于钦问.三氯羟基二苯醚复方消毒剂性能的试验观察[J].中国消毒学杂志,2001,18(3):154-157.
    [76]韩景文,王艳玲.强化戊二醛杀菌性能实验研究[J].内蒙预防医学,2000,25(1):19-20.
    [77]宋江南,陈贵秋.强化戊二醛复方消毒液性能的试验观察[J].实用预防医学,2002,9(5) 565-567.
    [78]卫生部卫生法制与监督司.消毒技术规范(2002)版[S].北京:中华人民共和国卫生部,2002.
    [79]王长德,张文福,芦毅,等.邻苯二甲醛杀菌效果影响因素的研究[J].中国消毒学杂志,2004,21(3):182-185.
    [80]李长清,邓小虹,高旭.邻苯二甲醛性能的试验观察[J].中国消毒学杂志,2003.20(4):261-264.
    [81]Rutala WA,Weber DJ.New disinfection and sterilization methods[J],Emerging Infectiongs Disease,2001,7(2):348-353.
    [82]Thereza Christina Vessoni penna,Priscila Gava Mazzola,Alzira Maria Silva martins.The efficacy of chemical agents in cleaning and disinfection programs[J].BMC Infection Diseases,2001,1:1-6.
    [83]Jean J,Vaehon JF,Moroni O,etal.Effectiveness of commercial disinfectants for inactivating hepatitis A virus on agri-food surfaces[J].Food prot,2003,66(1):115-119.
    [84]杨华明,易斌.现代医院消毒学[M].北京:人民军医出版社,2005.
    [85]许能锋,林立旺,徐文体,等.邻苯二甲醛杀灭枯草杆菌黑色变种芽孢效果及其影响因素的研究[J].中国消毒学杂志,2005.22(2):125-127.
    [86]Ficici SE,Durmaz G,Ilhan S,et aI.Baeterieidal effects of commonly antiseptics/disinfectants onnosocomial bacterial pathogens and antiseptics against nosocomial bacterial pathogens and the relationship between antibacterial and biocide resistance[J].Mikrobiyol bul,2002,36(3-4):259-69.
    [87]Jean J,Vachon JF,Moroni O,etal.Effectiveness of commercial disinfectants for inactivating hepatitis A virus on agri-food surfaces[J].Food prot,2003,66(1):115-119.
    [88]Martine C,Christine A,Jean-Lue B,et al.Virucidal Efficacy of Glutaraldehyde against Enteroviruses Is Related to the Location of Lysine Residues in Exposed Structures of the VPI Capsid Protein[J].Applied and environmental microbiology,2004,70(3):1717-1722.
    [89]Chan-Myers C.Effect of temperature and organic soil concentration on biocidal activity of ortho- phth alaldehyde solution[J].Infect Control and Hosp Epide miology,2000,21(8):548-551.
    [90]卫生部卫生法制与监督司.消霉技术规范(2002版)[S].北京:中华人民共和国卫生部,2002.
    [91]Guthua SW,Macigo FG,Mwaniki DL,et al.Symptoms in health personnel exposed to disinfectants [J].Afr Med,200 i,78(3):157-60.
    [92]Ballantyne B,Myers RC.The acute toxicity and primary irritancy of glytaraldehyde solutions[J].Vet Hum Toxicol,2001,43(4):193-202.
    [93]Vergnes JS,Ballantyne B.Genetic toxicology studies with glutaraidehyde[J].Appl Toxicol,2002,22(1):45-60.
    [94]Ravis SM,Shaffer MP,Shaffer CL,et al.Glutaraldehyde-induced and foraidehyde-induced allergic contact dermatitis among dental hygienists and assistants[J].Am Dent Assoc,2003,134(8):1072-1078.
    [95]李发亮,孙海滨,王江波,等.戊二醛消毒剂对局部组织损害的实验研究[J].中国消毒学杂志,2003,20(3):190-192.
    [96]夏勇,傅剑云,毛光明,等.戊二醛消毒剂对家兔阴道粘膜刺激作用的病理学观察[J].浙江预防医学,2004,16(8):75-76.
    [97]徐文体,许能锋.戊二醛杀灭菌作用及毒副反应研究进展[J].现代预防医学,2003,30(3):398-400.
    [98]林立旺,徐能峰.复方邻苯二甲醛的毒性与金属腐蚀性的研究[J].海峡预防医学杂志,2006,12(4):13-14.
    [99]Cooke RE Goddard SV,Whymant-Mords A,et al.An Evaluationof Cidex OPX(0.55%ortho-phthalaldehyde) as an alternative to 2%(v/v) glutaraldehyde for high -level disinfectiong of endoscopes[J].Hosp Ifect,2003,54(3):226-231.
    [100]Hession,Sandra M.Endoscope Disinfection by Ortho-phthalaldehyde in a Clinical Setting:An Evaluation of Reprocessing Time and Costs Compared With Glutaraidehyde[J].Gastroenterol Nurs,2003,26(3):110-114.
    [101]Proitti L,Longo B,Duscio S,et al.Environmental monitoring of occupational exposure to glutaraldehyde at a hospital[J].Ital Med Lav Ergon,2003,25(2):165-167.

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