Box-Behnken设计-响应面法优化猪源纤维蛋白原冻干保护剂
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摘要
目的通过Box-Behnken设计—响应面法优化猪源纤维蛋白原的冻干保护剂配比。方法以蔗糖、精氨酸和白蛋白为自变量,以粘合力和弹力的总评"归一值"作为因变量,通过对自变量各水平进行多元线性回归及二项式拟合,采用响应面法优选保护剂配方配比,并进行预测分析。结果精氨酸对纤维蛋白粘合剂力学性能的影响最为显著,其次是白蛋白。最优保护剂配方比为:蔗糖含量15.87 g·L-1、精氨酸含量7.87 g·L-1、白蛋白含量3.62 g·L-1。结论模型预测的粘合力值与真实值能较好的拟合,具有较高的精确度,说明该模型能有效地预测纤维蛋白胶体力学性能,优化所得的纤维蛋白原冻干处方工艺稳定可行。
FG is a type of biological protein adhesive with broad application prospects,including fibrinogen freeze-dried powders and thrombin freeze-dried powders. This article explored the effect of protective agents on the mechanical properties of fibrin gels during freeze-drying of fibrinogen preparations. The response surface method Box-Behnken design was adopted.Sucrose,arginine and albumin were selected as the influencing factors while adhesion and elasticity were the objects of investigation. The comprehensive index OD was used as the response value,and the regression analysis was used to establish a Quadratic multivariate model. The results showed that arginine showed the most significant effect on bulk mechanical properties,followed by albumin. The optimal protective agent formula was: sucrose content 15. 87 g·L-1,arginine content 7. 87 g·L-1,albumin content 3. 62 g·L-1. The predicted adhesion value and the actual value of the model cross-matched well,indicating that the model can effectively predict the mechanical properties of the fibrin gel.
FG is a type of biological protein adhesive with broad application prospects,including fibrinogen freeze-dried powders and thrombin freeze-dried powders. This article explored the effect of protective agents on the mechanical properties of fibrin gels during freeze-drying of fibrinogen preparations. The response surface method Box-Behnken design was adopted.Sucrose,arginine and albumin were selected as the influencing factors while adhesion and elasticity were the objects of investigation. The comprehensive index OD was used as the response value,and the regression analysis was used to establish a Quadratic multivariate model. The results showed that arginine showed the most significant effect on bulk mechanical properties,followed by albumin. The optimal protective agent formula was: sucrose content 15. 87 g·L-1,arginine content 7. 87 g·L-1,albumin content 3. 62 g·L-1. The predicted adhesion value and the actual value of the model cross-matched well,indicating that the model can effectively predict the mechanical properties of the fibrin gel.
引文
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[26]B Liu,X Zhou.Freeze-Drying of Proteins.Methods Mol Biol.2015,1257(1257):459-476.
[2]梁兵,田兆嵩.纤维蛋白粘合剂在手术中的应用.中国输血杂志,2008,21(11):896-898.
[3]高彦俊,许丽丽,王志平.纤维蛋白胶在泌尿外科手术中的应用.临床泌尿外科杂志,2014,29(12):1126-1131.
[4]Healy C,Greig AV,Murphy AD,et al.Prospective randomized controlled trial:fibrin sealant reduces split skin graft donor-site pain.Plastic and reconstructive surgery,2013,132(1):139-146.
[5]BurnoufRadosevich M,Burnouf T,Huart J.Biochemical and physical properties of a solventdetergenttreated fibrin glue.Voxsanguinis,1990,58(2):77-84.
[6]罗洁,王凤山.医用软组织粘合剂的研究进展及临床应用现状.药物生物技术,2014(3):274-278.
[7]蔡紫阳.药品冻干工艺的设计和优化原理.求医问药,2012,10(12):235.
[8]刘占杰,华泽钊.蛋白质药品冷冻干燥过程中变性机理的研究进展.中国生化药物杂志,2000,21(5):263-265.
[9]王洁,黄传伟,安源,等.真空冷冻干燥的工艺流程.医疗卫生装备,2012,33(9):90-91.
[10]武华丽,胡一桥.冷冻干燥制剂的稳定性研究进展.中国药学杂志,2001,36(7):436-438.
[11]慕运动.响应面方法及其在食品工业中的应用.郑州工程学院学报,2001(3):91-94.
[12]Montgomery DC.Design and analysis of experiments.3rded.New York:John Wiley Sons,2017.
[13]Maleki H,Gharehaghaji AA,Criscenti G,et al.The influence of process parameters on the properties of electrospun PLLA yarns studied by the response surface methodology.Journal of Applied Polymer Science,2015,132(5):325-336.
[14]Bergel S.Ueberwirkungen des fibrins.DMWDeutsche Medizinische Wochenschrift,1909,35(15):663-665.
[15]刘爱民,黄松林.单一人份纤维蛋白胶的制备、性能及止血效果观察.中国输血杂志,1999,12(1):15-17.
[16]Cleland JL,Langer R.Formulation and delivery of proteins and peptides:American Chemical Society Washington,DC,USA:1994,78(1):58-60.
[17]Carpenter JF,Chang BS.Lyophilization of protein pharmaceuticals.Biotechnology and biopharmaceutical manufacturing,processing,and preservation,1996,2(3):199-264.
[18]宫川真一,荒木辰也,羽室强,等.固体纤维蛋白原制剂,CN,10167806B,2013.
[19]安康,马小伟,潘若文,等.一种冻干人纤维蛋白胶生产工艺,CN,1207064C,2005.
[20]Kawai H,Sakurai M,I noue Y,et al.Hydration of Oligosaccharides:Anomalous Hydration A bility of Trehalose.Cryobiology,1992,29(5):599-606.
[21]Khanlou HM,Sadollah A,Ang BC,et al.Prediction and optimization of electrospinning parameters for polymethyl methacrylate nanofiber fabrication using response surface methodology and artificial neural networks.Neural Computing and Applications,2014,25(3):767-777.
[22]国家药典委员会.中华人民共和国药典[2015年版].北京:北京工业出版社,238-239.
[23]田烨,吴明媛.生物制品冻干保护方法研究进展.中国医药生物技术,2018,13(1):73-75.
[24]方志正,何建中.应用正交试验研究麻疹疫苗保护剂和冻干条件.中国生物制品学杂志,1997,10(2):101-104.
[25]马海燕,王世聪,郄正刚.重组人血白蛋白在药用辅料中的应用.中国生物制品学杂志,2014,27(10):1359-1360.
[26]B Liu,X Zhou.Freeze-Drying of Proteins.Methods Mol Biol.2015,1257(1257):459-476.