淀粉基水分散体薄膜包衣材料及其释放行为的研究
|
摘要
近年来,随着现代科学技术的飞速发展及药物制剂理论的不断更新,极大地促进了药物新剂型的发展,使得药物制剂的研究已从简单的传统剂型进入到药物传递系统时代。特别是口服缓控释给药系统更是凭借其较高的用药安全性和生物利用度已经成为当今医药工业发展的一个重要方向。由此而引起的研制和开发适合的新型载体材料及相关制剂技术,建立有效的给药体系已成为当前制药业的迫切任务。因此,开发适合水分散体薄膜包衣的淀粉口服药物缓控释载体材料和包衣技术既符合现代给药系统的发展趋势,也能拓宽淀粉在医药领域的应用,具有重大的理论意义和经济价值。
采用高温高压-酶解协同修饰方法对淀粉进行改性,获得重均聚合度范围较宽的改性淀粉,使其符合缓控释给药系统的要求;并利用多功能显微、傅里叶变换红外光谱分析、X-射线衍射、小角X-射线散射和凝胶渗透色谱-激光光散射联用等技术对改性前后的淀粉结构和性质进行研究。
以改性淀粉作为微丸薄膜包衣的新材料,根据水分散体薄膜包衣材料的制备要求及其包衣特点,研究了淀粉基水分散体的流变学规律、粒径、稳定性等性质。采用流延法制备淀粉游离膜,并对其成膜性、透湿性以及在模拟人工胃液和模拟人工肠液中的消化性能进行了研究,建立了适合水分散体薄膜包衣的淀粉包衣液体系。
以5-氨基水杨酸和胰岛素为模型药物,采用挤出滚圆技术制备载药丸芯,探索了包衣条件对包衣效果及微丸释药性能的影响,建立了低温水分散体包衣技术,在研究各种因素对制剂成型的影响和优化制剂工艺的基础上,构建淀粉基水分散体薄膜包衣缓控释微丸新型给药系统。体外模拟实验结果表明,当以水为溶剂,选取重均分子量为3.07×10~4g/mol的改性淀粉作为薄膜包衣材料,包衣液固含量为8%(w/w),选择1,2-丙二醇作为增塑剂,其添加量为10%(w/w),控制包衣增重量为30%(w/w),所制得的薄膜包衣微丸无论是载小分子的化学药物还是多肽蛋白质大分子药物,在模拟人工胃液和人工小肠液中的释药率约为28.26%,在模拟结肠环境中释放30h后释药率可达90%左右,表明所制备的改性淀粉基水分散体薄膜包衣微丸具有良好的缓控释释药性能,其释药机制主要为扩散控制释放机制以及渗透压驱动作用协同机制,释药速率取决于淀粉膜的结构与性质、包衣厚度、模型药物分子量及其在溶出介质中的溶解性、衣膜中的扩散性等。所建立的释药动力学方程符合零级动力学模型、Ritger peppas方程和Logistic模型。
采用Ⅱ型糖尿病大鼠模型和先进的免疫组化技术,对载体材料和给药系统在大鼠消化道中的药物释放行为和药效学等进行验证和评价。研究结果表明,在同等有效的胰岛素剂量水平下,淀粉基水分散体薄膜包衣胰岛素微丸制剂则呈现出较好的药物缓控释性能,无“血糖波动”和“低血糖”现象出现,释放规律良好,与体外模拟实验结果趋势一致。
本论文以自然界中资源丰富和生物相容性好的高直链玉米淀粉作为研究对象,通过物理重组协同酶修饰技术,获得了具有良好耐酸和耐酶解性能的改性淀粉,以其作为水分散体薄膜包衣载体材料所构建的膜控型微丸给药系统具有良好的药物缓控释性能,能够保护药物生理活性,延长药物释放时间,提高药物给药效果。这将为淀粉作为水分散体包衣薄膜以满足药物在消化道的缓控释放奠定了基础,也为淀粉深加工及可再生资源的高附加值利用提供了新的思路。
In recent years, the rapid development of modern science and technology and the update of pharmaceutical preparations theories greatly promoted the development of new drugs formulations, which pushed the study of pharmaceutical preparations from a simple-traditional form to a drug delivery system. In particular, oral sustained and controlled release delivery system has become an important direction of pharmaceutical industry due to its high drug safety and bioavailability. Development of new carrier materials and related preparation technologies, establishment of effective drug delivery systems have become an urgent tasks for the pharmaceutical industry. Based on these requirements,the development of suitable starch-based aqueous dispersion film coating sustained and controlled release carrier materials and coating technology are in line with the trend of modern drug delivery systems, and can also expand the application in the pharmaceutical field of starch, have both great scientifical importance and commercial value.
Various weight-average degree of polymerization of modified starch were obtained by using high temperature and high pressure-enzyme collaborative method to meet the requirements of sustained and controlled release drug delivery systems.The structure and properties of modified starch were studied by multi-functional microscope, fourier transform infrared spectroscopy, X-ray diffraction, small angle X-ray scattering and gel permeation chromatography-laser light scattering techniques.
As new film coating materials from the modified stach, the rheology, particle size, stability and other properties of the starch-based aqueous dispersion were studied according to preparation requirements and coating characteristics of aqueous dispersion film coating material. Free starch films were prepared by using cast method, the film-forming properties, moisture and digestive properties in simulated human gastric and small intestinal fluid were also studied. A suitable starch-based aqueous dispersion film coating system was developed.
Using 5-amino salicylic acid and insulin as model drugs, the drugs pellets were prepared by extrusion-spheronisation. The effect of coating conditions on the coating and the release properties were investigated, the low temperature aqueous dispersion coating technology was established. The starch-based aqueous dispersion film coating sustained and controlled drug delivery system was constructed on the base of investigation of the influence of different factors on the formation of the drug delivery system and optimization of the preparation processes. The results from in-vitro tests indicated that the constructed drug delivery system was suitable for delivering not only the small molecular chemical drug but also biomacromolecule drugs, when using water as solvent, the weight average molecular weight 3.07×104g/moL of modified starch as film coating materials, solid content of 8% (w / w) ,1,2 -propylene glycol as a plasticizer and its addition level of 10%(w/w), coating weight of 30%(w/w), the drug release of approximately 28.26% in simulated gastric fluid and small intestinal fluid, after 30h the release about 90% in the simulated colon fluid, providing with good sustained and controlled performance. The release mechanism are mainly diffusion controlled release mechanism and osmotic pressure-driven coordinative mechanism, The drug release rate depends on the structure and properties of starch films, coating thickness, the molecular weight of a model drug and its solubility in the dissolution medium, the diffusion in the coating films. The established dynamic equation corresponds to zero order release kinetic model, ritger peppas equation and logistic models.
The typeⅡdiabetic rat m odel and advanced im m unohisto-chemistry technology were used to validate and evaluat the releasing properties and pharmacodynamics of carrier materials as well coated pellets in the rat gastrointestinal tracts. The results suggest that starch-based aqueous dispersion film coating insulin pellets have a good drug release performance at the same effective dose of insulin, have no blood glucose fluctuations phenomenon and low blood glucose phenomenon, and have the same trend with in-vitro results.
In this thesis, use high amylose corn starch which rich in nature and has good biocompatibility as a research object, good resistance to acid and enzyme properties of modified starch was obtained by physical restructuring-enzyme collaborative method. The modified starch as aqueous dispersion film coating carrier constructed film-controlled pellet delivery system and protected the physiological activity of drugs, prolonged drug release time and improve the administration effect of drug. This work not only provides foundation for aqueous dispersion coating film to meet sustained and cotrolled drug release in the digestive tract, but also provides a new way of the deep-applications of starch. Furthermore, materials from the renewable resources will be utilized as a higher value product.
采用高温高压-酶解协同修饰方法对淀粉进行改性,获得重均聚合度范围较宽的改性淀粉,使其符合缓控释给药系统的要求;并利用多功能显微、傅里叶变换红外光谱分析、X-射线衍射、小角X-射线散射和凝胶渗透色谱-激光光散射联用等技术对改性前后的淀粉结构和性质进行研究。
以改性淀粉作为微丸薄膜包衣的新材料,根据水分散体薄膜包衣材料的制备要求及其包衣特点,研究了淀粉基水分散体的流变学规律、粒径、稳定性等性质。采用流延法制备淀粉游离膜,并对其成膜性、透湿性以及在模拟人工胃液和模拟人工肠液中的消化性能进行了研究,建立了适合水分散体薄膜包衣的淀粉包衣液体系。
以5-氨基水杨酸和胰岛素为模型药物,采用挤出滚圆技术制备载药丸芯,探索了包衣条件对包衣效果及微丸释药性能的影响,建立了低温水分散体包衣技术,在研究各种因素对制剂成型的影响和优化制剂工艺的基础上,构建淀粉基水分散体薄膜包衣缓控释微丸新型给药系统。体外模拟实验结果表明,当以水为溶剂,选取重均分子量为3.07×10~4g/mol的改性淀粉作为薄膜包衣材料,包衣液固含量为8%(w/w),选择1,2-丙二醇作为增塑剂,其添加量为10%(w/w),控制包衣增重量为30%(w/w),所制得的薄膜包衣微丸无论是载小分子的化学药物还是多肽蛋白质大分子药物,在模拟人工胃液和人工小肠液中的释药率约为28.26%,在模拟结肠环境中释放30h后释药率可达90%左右,表明所制备的改性淀粉基水分散体薄膜包衣微丸具有良好的缓控释释药性能,其释药机制主要为扩散控制释放机制以及渗透压驱动作用协同机制,释药速率取决于淀粉膜的结构与性质、包衣厚度、模型药物分子量及其在溶出介质中的溶解性、衣膜中的扩散性等。所建立的释药动力学方程符合零级动力学模型、Ritger peppas方程和Logistic模型。
采用Ⅱ型糖尿病大鼠模型和先进的免疫组化技术,对载体材料和给药系统在大鼠消化道中的药物释放行为和药效学等进行验证和评价。研究结果表明,在同等有效的胰岛素剂量水平下,淀粉基水分散体薄膜包衣胰岛素微丸制剂则呈现出较好的药物缓控释性能,无“血糖波动”和“低血糖”现象出现,释放规律良好,与体外模拟实验结果趋势一致。
本论文以自然界中资源丰富和生物相容性好的高直链玉米淀粉作为研究对象,通过物理重组协同酶修饰技术,获得了具有良好耐酸和耐酶解性能的改性淀粉,以其作为水分散体薄膜包衣载体材料所构建的膜控型微丸给药系统具有良好的药物缓控释性能,能够保护药物生理活性,延长药物释放时间,提高药物给药效果。这将为淀粉作为水分散体包衣薄膜以满足药物在消化道的缓控释放奠定了基础,也为淀粉深加工及可再生资源的高附加值利用提供了新的思路。
In recent years, the rapid development of modern science and technology and the update of pharmaceutical preparations theories greatly promoted the development of new drugs formulations, which pushed the study of pharmaceutical preparations from a simple-traditional form to a drug delivery system. In particular, oral sustained and controlled release delivery system has become an important direction of pharmaceutical industry due to its high drug safety and bioavailability. Development of new carrier materials and related preparation technologies, establishment of effective drug delivery systems have become an urgent tasks for the pharmaceutical industry. Based on these requirements,the development of suitable starch-based aqueous dispersion film coating sustained and controlled release carrier materials and coating technology are in line with the trend of modern drug delivery systems, and can also expand the application in the pharmaceutical field of starch, have both great scientifical importance and commercial value.
Various weight-average degree of polymerization of modified starch were obtained by using high temperature and high pressure-enzyme collaborative method to meet the requirements of sustained and controlled release drug delivery systems.The structure and properties of modified starch were studied by multi-functional microscope, fourier transform infrared spectroscopy, X-ray diffraction, small angle X-ray scattering and gel permeation chromatography-laser light scattering techniques.
As new film coating materials from the modified stach, the rheology, particle size, stability and other properties of the starch-based aqueous dispersion were studied according to preparation requirements and coating characteristics of aqueous dispersion film coating material. Free starch films were prepared by using cast method, the film-forming properties, moisture and digestive properties in simulated human gastric and small intestinal fluid were also studied. A suitable starch-based aqueous dispersion film coating system was developed.
Using 5-amino salicylic acid and insulin as model drugs, the drugs pellets were prepared by extrusion-spheronisation. The effect of coating conditions on the coating and the release properties were investigated, the low temperature aqueous dispersion coating technology was established. The starch-based aqueous dispersion film coating sustained and controlled drug delivery system was constructed on the base of investigation of the influence of different factors on the formation of the drug delivery system and optimization of the preparation processes. The results from in-vitro tests indicated that the constructed drug delivery system was suitable for delivering not only the small molecular chemical drug but also biomacromolecule drugs, when using water as solvent, the weight average molecular weight 3.07×104g/moL of modified starch as film coating materials, solid content of 8% (w / w) ,1,2 -propylene glycol as a plasticizer and its addition level of 10%(w/w), coating weight of 30%(w/w), the drug release of approximately 28.26% in simulated gastric fluid and small intestinal fluid, after 30h the release about 90% in the simulated colon fluid, providing with good sustained and controlled performance. The release mechanism are mainly diffusion controlled release mechanism and osmotic pressure-driven coordinative mechanism, The drug release rate depends on the structure and properties of starch films, coating thickness, the molecular weight of a model drug and its solubility in the dissolution medium, the diffusion in the coating films. The established dynamic equation corresponds to zero order release kinetic model, ritger peppas equation and logistic models.
The typeⅡdiabetic rat m odel and advanced im m unohisto-chemistry technology were used to validate and evaluat the releasing properties and pharmacodynamics of carrier materials as well coated pellets in the rat gastrointestinal tracts. The results suggest that starch-based aqueous dispersion film coating insulin pellets have a good drug release performance at the same effective dose of insulin, have no blood glucose fluctuations phenomenon and low blood glucose phenomenon, and have the same trend with in-vitro results.
In this thesis, use high amylose corn starch which rich in nature and has good biocompatibility as a research object, good resistance to acid and enzyme properties of modified starch was obtained by physical restructuring-enzyme collaborative method. The modified starch as aqueous dispersion film coating carrier constructed film-controlled pellet delivery system and protected the physiological activity of drugs, prolonged drug release time and improve the administration effect of drug. This work not only provides foundation for aqueous dispersion coating film to meet sustained and cotrolled drug release in the digestive tract, but also provides a new way of the deep-applications of starch. Furthermore, materials from the renewable resources will be utilized as a higher value product.
引文
[1] Duncan R. The dawning era of polymer therapeutics[J]. Nature Reviews Drug Discovery, 2003, 3: 347-360.
[2] El-Malah Y, Khanfar N.M, Nazzal S. D-optimal mixture design optimization of ternary matrix blends for controlled zero-order drug release from oral dosage forms[J]. Drug Development and Industrial Pharmacy, 2006, 32(10): 1207-1218.
[3] Chidambaram N, Porter W, Flood K, et al. Formulation and characterization of new layered diffusional matrices for zero-order sustained release[J]. Journal of Controlled Release, 1998, 52(1-2): 149-158.
[4] Freiberg S, Zhu X.X. Polymer microspheres for controlled drug release[J]. International Journal of Pharmaceutics, 2004, 282(1): 1-18.
[5] Kafedjiiskik K, Krauland A. H, Hoffer M. H, et al. Synthesis and in vitro evaluation of a novel thiolated chitosan[J]. Biomaterials, 2005, 26(7): 819-826.
[6] El-Malah Y, Nazzal S. Fluid bed coating: The utility of dual programmable pumps for controlled gradient drug deposition on pellets[J]. International Journal of Pharmaceutics, 2007, 337(1-2): 361-364.
[7] Martinez-Floresa H.E, Changb Y.K, Martinez-bustosc F, et al. Effect of high fiber products on blood lipids and lipoproteins in hamsters[J]. Nutrition Research, 2004, 24(1): 85-93.
[8] Joseph R. Controlled Drug Delivery: Fundamentals and Applications[M]. Second Edition. USA. Marcel Dekker. INC, 1987: 7-9.
[9] Langer R. New methods of drug delivery[J]. Science, 1990, 249(4976): 1527-1533.
[10] Vasilevska K, Djuric Z, Jovanovic M, et al. Preparation and dissolution characteristics of controlled release diltiazem pellets[J]. Drug Development and Industrial Pharmacy, 1992, 18(15): 1649-1661.
[11]盛朝晖.口服缓控释制剂临床评价[J].中国医院药学杂志, 2005, 25(6): 558-559.
[12]张政朴.反应性与功能性高分子材料[M].北京:化学工业出版社, 2005: 26-30.
[13]杨延昆,王玉玲.药物缓释、控释制剂的研究开发现状及发展趋势[J].齐鲁药事, 2004, 23(4): 31-32.
[14] Li Y.H, Zhu J.B. Modulation of combined-release behavious from a novel tables-in-capsule system[J]. Journal of Controlled Release, 2004, 95(3): 381-382.
[15] Ramakrishna N, Mishra B. Plasticizer effect and comparative evaluation of cellulose acetate and ethylcellulose HPMC combination coatings as semipermeable membranes for oral osmotic pumps of naproxensodium[J]. Drug Development and Industrial Pharmacy, 2002, 28(4): 403-412.
[16] Yan G, Li H.N, Zhang R.H, et al. Preparation and evaluation of a sustained-release formulation of nifedipine HPMCT ablets[J]. Drug Development and Industrial Pharmacy, 2000, 26(6): 681-686.
[17] Kulkarni R.V, Mangond B.S, Mutalik S, et al. Interpenetrating polymer network microcapsules of gellan gum and egg albumin entrapped with diltiazem-resin complex for controlled release application[J]. Carbohydrate Polymers, 2011, 83(2): 1001-1007.
[18] Kumaravelrajana R, Narayananb N, Subac V, et al. Simultaneous delivery of Nifedipine and Metoprolol tartarate using sandwiched osmotic pump tablet system[J]. International Journal of Pharmaceutics, 2010, 399(1-2): 60-70.
[19] Kearney A.S. Prodrugs and targeted drug delivery[J]. Advanced Drug Delivery Reviews, 1996, 19(2): 225-239.
[20] Zhang X.R, Wang Y, Yin F.Q, et al. Study on preparation of total salvianolic acid gastricresidential tablets[J]. Chinese Traditional Patent Medicine, 2003, 25(5): 349-350.
[21] Bharaniraja B, Jayaram K, Prasad C.M, et al. Modified Katira Gum for Colon Targeted Drug Delivery[J]. Journal of Applied Polymer Science, 2011, 119(5): 2644-2651.
[22] Sangalli M. E, Maroni A, Zema L, et al. In vitro and in vito evaluation of an oral system for time and/or site-specific drug delivery[J]. Journal of Controlled Release, 2001, 73(1): 103-110.
[23] Kopecek J. Smart and genetically engineered biomaterials and drug delivery systems[J]. European journal of pharmaceutical sciences, 2003, 20(1): 1-16.
[24]陈丽华,冯怡,徐德生.中药缓控释微丸制剂的研究进展[J].中国中药杂志, 2007, 6(32): 472-475.
[25]唐星.口服缓控释制剂[M].北京:人民卫生出版社, 2007: 97-100.
[26]邓恒兵,李传枚.国内缓控释微丸制剂的研究进展[J].药学实践杂志, 2003, 3 (24): 132-135.
[27]阳长明,侯世祥,张志荣,等.缓释与控释小丸的研究进展[J].华西药学杂志, 2001, 16(2): 121.
[28]宋洪涛,郭涛,陈大为,等.多元定位释药技术制备舒胸缓释胶囊的研究[J].中草药,2005, 36(7): 993-998.
[29]张晓辉.盐酸地尔地卓缓释脉冲微丸的研制[D].河北:河北医科大学, 2006.
[30] Serraton M, Newton M, Booth S. Controlled drug release from pellets containing water insoluble drugs dissolved in a self-emulsifying system[J]. European Journal of Pharmaceutics and Biopharmaceutics, 2007, 65(1): 94-98.
[31] Marucc M, Ragnarsson I.G, Axelsson A. Evaluation of osmotic effects on coated pellets using amechanisticmodel[J]. International Journal of Pharmaceutics, 2007, 336(1): 67-74.
[32]王宪英,李焕博.薄膜包衣技术概述[J].中国药业, 1999, 8(9): 63-64.
[33] McGinity J.W. Aqueous polymeric coatings for pharmaceutical dosage forms[M]. New York: Marcel Dekker, 1997: 11-20.
[34] Frohoff-Hu¨lsman M. A. , Schmitz A. , Lippold B. C. Aqueous ethyl cellulose dispersions containing plasticizers of different water solubility and hydroxypropyl methylcellulose as coating material for diffusion pellets I. Drug release rates from coated pellets[J]. International Journal of Pharmaceutics, 1999, 177(1): 69-82.
[35]陈挺,陈庆华.聚合物水分散体包衣技术及其应用[J].中国现代应用药学, 2000,17(5): 339-343.
[36] Marcel V, Jozua L, Anton L.G. Current understanding of the deformation of latex particles during film formation[J]. Progress in organic coatings, 1997, 30(1-2): 39-49.
[37] Brondsted H. Hydrogels for site-specific oral drug delivery[J]. Biomaterial, 1995, 12(6): 548-592.
[38]张继稳,顾景凯.缓控释制剂药物动力学[M].北京:科学出版社, 2009: 27-38.
[39]黄雁,何希文,揣成智.乙基纤维素水分散体在缓控释薄膜包衣领域中的应用[J].塑料, 2007, 36(3): 37-40.
[40] Lecomte F, Siepmanna J, Waltherb M, et al. Polymer blends used for the aqueous coating of solid dosage forms: importance of the type of plasticizer[J]. Journal of Controlled Release, 2004, 99(1): 1-13.
[41]张军颖,杨梅.对薄膜包衣技术问题的探讨[J].中国医药导报, 2009, 6(7): 6-9.
[42] Shah N.H, Zhang L, Railkar A, et al. Factors affecting the kinetics and mechanism of release of glazapril from beadlets coated with aqueous and nonaqueous ethylcellulose-based coatings[J]. Pharmaceutical Technology, 1994, 18(10): 140-148.
[43] Derbin G.M, Palsson B.O, Mansfield J.F, et al. Release behavior from ethylcellulose-coated pellets: Thermomechanical and electron microbeam studies[J].Pharmaceutical Technology, 1996, 20(9): 70-80.
[44] Cole G, Hogan J, Aulton M. Pharmaceutical coating technology[M].北京:中国医药科技出版社,2000:51-61.
[45]罗明生,高天惠.药剂辅料大全[M].成都:四川科学出版社, 1993: 88-89.
[46]杜月莲.高分子材料在薄膜包衣中的应用[J].山西职工医学院学报, 2003, 13(4): 56-57.
[47] Porter S.C. Controlled-release film coatings based on ethylcellulose[J]. Drug Development and Industrial Pharmacy, 1989, 15(10): 1496-1521.
[48] Rowe R, Sheskey P.J, Weller P. Handbook of Pharmaceutical Excipients[M]. UK: Pharmaceutical Press, 2003: 237-241.
[49] Muschert S. , Siepmann F. , Leclercq B. , et al.Drug release mechanisms from ethylcellulose: PVA-PEG graft copolymer-coated pellets[J]. European Journal of Pharmaceutics and Biopharmaceutics, 2009, 72(1): 130-137.
[50] Muschert S, Siepmann F, Leclercq B, et al. Prediction of drug release from ethylcellulose coated pellets[J]. Journal of Controlled Release, 2009, 135(1): 71-79.
[51] Siepmann F, Hoffmann A, Leclercq B, et al. How to adjust desired drug release patterns from ethylcellulose-coated dosage forms[J]. Journal of Controlled Release, 2007, 119(2): 182-189.
[52] Karrout Y, Neut C, Wils D, et al. Novel polymeric film coatings for colon targeting:How to adjust desired membrane properties[J]. International Journal of Pharmaceutics, 2009, 371(1-2): 64-70.
[53]张瑜,孙茂峰.乙基纤维素水分散体包衣技术[J].中国医院药学杂志, 2002, 22(1): 49-50.
[54] Chang R.K. A review of aqueous coating techniques and preliminary data on release from a theophylline product[J]. Pharmaceutical Technology, 1987, 3(2): 56-68.
[55]傅崇东,徐惠南,张瑜. 5-氨基水杨酸结肠定位给药时控微丸的制备与体外释放[J].药学学报, 2000, 27(5): 389-393.
[56] Wesseling M, Bodmeier R. Drug release from beads coated with an aqueous colloidal ethylcellulose dispersion Aquacoat○R
[57] Gilligan C.A, Li Wan Po A. Factors affecting drug release from a pellet system coated or an organic ethylcellulose solution[J]. European Journal of Pharmaceutics and Biopharmaceutics,1999, 47(1):33-38.with an aqueous colloidal dispersion[J]. International Journal of Pharmaceutics, 1991, 73(1): 51-68.
[58] Bonacucina G, Martino P.D, Piombetti M, et al. Effect of plasticizers on properties of pregelatinised starch acetate (Amprac 01) free films[J]. International Journal of Pharmaceutics, 2006, 313(1-2): 72-77.
[59] Tarvainen M, Peltonen S, Mikkonen H, et al. Aqueous starch acetate dispersion as a novel coating material for controlled release products[J]. Journal of Controlled Release, 2004, 96(1): 179-191.
[60]陆彬.药物新剂型与新技术[M].第二版.北京:人民卫生出版社, 2005:20-26.
[61]刘欣,薛红梅,王建明,等.盐酸小檗碱结肠定位包衣片的制备工艺和体外释放研究[J].世界科技研究与发展, 2008, 30(3):347-351.
[62] Kaur K, Kim K. Studies of chitosan/organic acid/Eudragit? RS/RL-coated system for colonic delivery[J]. International Journal of Pharmaceutics, 2009, 366(1-2):140-148.
[63] Siepmann F, Siepmann J, Walther M, et al. Polymer blends for controlled release coatings[J]. Journal of Controlled Release, 2008, 125(1):1-15.
[64]韩海岭,丁宇,柴佩华,等. Eudragit L30D-55和NE30D在软胶囊肠溶包衣中的应用[J].中国医药工业杂志, 2008, 39(6):432-434
[65] Song H, Guo T, Zhang R, et al. Preparation of the traditional Chinese medicine compound recipe heart-protecting musk pH-dependent gradient-release pellets[J]. Drug Development and Industrial Pharmacy, 2002, 28(10):1261-1273.
[66]张立超,胡晋红.聚合物水分散体包衣技术的进展.药学实践杂志[J]. 1999, 17(3):144-148.
[67] CuráJ.A, Jansson P.E, Krisma C.R. Amylose is not strictly linear[J]. Starch/St? rke, 1995, 47(6):207-209.
[68] Manners D.J. Recent developments in our understanding of amylopectin structure[J]. Carbohydrate Polymers, 1989, 11(2):87-112.
[69] Biliaderis C.G. Structures and phase transitions of starch polymers[M]. In: Walter, R.H.(Ed.). Polysaccharide Association Structures in Foods. Marcel Dekker, New York: 1998: 57-168.
[70] Tester R.F, Karkalas J, Qi X. Starch-composition, fine structure and architecture[J]. Journal of Cereal Science, 2004, 39(2):151-165.
[71] Tahir R, Ellis P.R, Bogracheva T.Y, et al. Study of the structure and properties of native and hydrothermally processed wild-type, lam and r variant pea starches that affect amylolysis of these starches[J]. Biomacromolecules, 2011, 12(1):123-133.
[72] Kim H.S, Huber K.C. Physicochemical properties and amylopectin fine structures of A- and B-type granules of waxy and normal soft wheat starch[J]. Journal of Cereal Science, 2010, 51(3):256-264.
[73]二国二郎.淀粉科学手册[M].北京:中国轻工业出版社,1990:21-151.
[74] Tester R.F, Karkalas J, Qi X. Starch-composition, fine structure and architecture[J]. Journal of Cereal Science, 2004, 39(2):151-165.
[75] Muhrbeck P. On crystallinity in cereal and tuber starches[J]. Starch/St?rke, 1991, 43 (9):347-348.
[76]张燕萍.变性淀粉的制造与应用(第一版)[M].北京:化学工业出版社, 2001:70-71.
[77] AllahM A, Foda Y.H, Mahmoud R.M. X-ray diffraction of starches isolated from yellow corn, sorghum, sordan and pearlmillet[J]. Starch/St?rke, 1987, 39(2):40-42.
[78] Gernat C, Tadosta S, Damaschun G. Supra-molecular structure of legume starches revealed by X-ray scattering[J]. Starch/St?rke, 1990, 42(5):175-178.
[79]王宏志,王永利.抗性淀粉的研究[J].甘肃科技, 2010, 26(6):46-47.
[80]李晓玺,陈玲,邹芳建,等.微波改性高链玉米淀粉颗粒的抗消化性能与结晶结构的关系[J].粮食与饲料工业, 2007,(12):12-17.
[81]张华东,张淼,沈晓萍,等.微波-酶法制备RS3型玉米抗性淀粉工艺参数优化研究[J].食品科学, 2007, 28(4):237-240.
[82] Chung H.J, Jeong H.Y, Lim S.T. Effects of acid hydrolysis and defatting on crystallinity and pasting properties of freeze-thawed high amylose corn starch[J]. Carbohydrate Polymers, 2003, 54(4):449-45.
[83]陈玲,卢声宇,温其标.羧甲基化对淀粉消化性能和抗酶解性能的影响[J].华南理工大学学报, 1999, 27(6):79-84.
[84]李晓玺,温其标,陈玲.三氯氧磷交联木薯淀粉的消化性能和酶降解程度.化学工程[J]. 2002, 30(4):45-55.
[85]李晓玺,陈玲,温其标,等.醋酸酯化对淀粉生物降解性能的影响[J].现代化工, 2002, 22(S1):139-142.
[86] Seib P.A, Woo K. Food grade starch resistant to alpha-amylase and method of preparingthe same[P]. US: 5 855 946.
[87] Thompson D.B. Strategies for the manufacture of resistant starch[J]. Trends in Food Science & Technology, 2000, 11(7):245-253.
[88] Sang Y.J, Seib P.A. Resistant starches from amylose mutants of corn by simultaneous heat-moisture treatment and phosphorylation[J]. Carbohydrate Polymers, 2006, 63(2):167-175.
[89] Gonzalez-soto R.A, Mora-escobedo R, Hernandez-Sandez H. The influence of time and storage temperature on resistant starch formation from autoclaved debranched banana starch[J]. Food Research International, 2007, 40(2):304-310.
[90] Pongjanta J, Utaipattanaceep A, NaivikulO, et al. Debranching enzyme concentration effected on physicochemical properties andα-amylase hydrolysis rate of resistant starch type III from amylose rice starch[J]. Carbohydrate Polymers, 2009, 78(1):5-9.
[91] Guraya H.S, James C, Champagne T. Effect of cooling and freezing on the digestibility of debranched non-waxy and waxy starch and physical properties of the resulting material[J]. Starch/ St?rke, 2011, 53(2):64-74.
[92] Yin H, Alias L, Karim A, et al. Effect of pullulanase debranching of Sago starch at subgelatinization temperature on the yield of resistant starch[J]. Starch/ St?rke, 2007, 59(1):21-32.
[93] Vihinen M, Mantsalap. Microbial amylolytic enzymes[J]. Critical Reviews in Biochemistry and Molecular Biology, 1989, 24(4):329-418.
[94]Yao W.R, Yao H.Y. Absorbent characteristics of porous starch[J]. Starch/St?rke, 2002, 54(6):260-263.
[95] Martin E.M. Cyclodextrins and their uses: a review[J]. Process Biochemistry, 2004, 39(9):1033-1046.
[96] Shin S.I, Choi H.J, Chung K.M, et al. Slowly digestible starch from debranched waxys or ghum starch: preparation and properties[J]. Cereal Chemistry, 2004, 81(3):404-408.
[97] Nabais T, Brouillet F, Kyriacos S, et al. High-amylose carboxymethyl starch matrices for oral sustained drug-release: In vitro and in vivo evaluation[J]. European Journal of Pharmaceutics and Biopharmaceutics, 2007, 65(3):371-378.
[98] Onofre F.O, Wang Y.J. Hydroxypropylated starches of varying amylose contents as sustained release matrices in tablets[J]. International Journal of Pharmaceutics, 2010, 385(1-2):104-112.
[99] Chen L, Li X.X, Pang Y.S, et al. 1st Chinese-European Symposium on Biomaterials[J]. Suzhou, 2006.
[100] Wang X.Y, Li X.X, Chen L, et al. Preparation and characterisation of octenyl succinate starch as a delivery carrier for bioactive food components[J]. Food Chemistry, 2011, 126(3):1218-1225.
[101] Clausen A.E,Bernkop-Schnürch A. Direct compressible polymethacrylic acid-starch compositions for site-specific drug delivery[J]. Journal of Controlled Release, 2001, 75(1-2):91-102.
[102]陈立新,陈茜.淀粉作为药物载体的研究现状及应用[J].中国组织工程研究与临床康复, 2010, 14(21):3943-3944.
[103]王雪毓,何小维,黄强,等.淀粉微球的研究与开发进展[J].食品研究与开发, 2009, 30(7):155-158.
[104]沈小玲,孙庆元,蒙敏,等.一种新型兽药载体-淀粉微球的制备及其特性[J].河南农业科学, 2008(2):111-114.
[105] Yu D.M, Xiao S.Y, Tong C.Y, et al. Dialdehyde starch nanoparticles: Preparation and application in drug carrier[J]. Chinese Science Bulletin, 2007, 52(21):2913-2918.
[106] Vervoort , Van den Mooter G, Augustijins P, et al. Inulin hydrogels as carriersfor colonic drugtargeting:ⅠSynthesis and characterization of methacrylated inulin and hydrogel formation[J]. Pharmaceutical research, 1997, 14(12):1730-1737.
[107] Maris B, Verheyden L, Van Reeth K, et al. Synthesis and characterization of inulinazo hydrogels designed for colon targeting[J]. International Journal of Pharmaceutics, 2001, 213(1-2):143-152.
[108] Wang XY, Chen L, Li XX, et al. Thermal and Rheological Properties of Breadfruit Starch[J]. Journal of Food Science, 2011, 76(1): 55-61.
[109]张光华.猴面包果肉配制恒释茶碱和扑热息痛片的生物利用度[J].国外医药(植物药分册), 1990, 5(4):186-187.
[110] Milojevic S, Newton J.M, Cummings J.H, et al. Amylose as a coating for drug delivery to the colon: preparation and in vitro evaluation using 5-aminosalicylic acid pellets[J]. Journal of Controlled Release, 1996a, 38(1):75-84.
[111] Milojevic S, Newton J.M, Cummings J.H, et al. Amylose as a coating for drug delivery to the colon: preparation and in vitro evaluation using glucose pellets[J]. Journal of ControlledRelease, 1996b, 38(1):85-94.
[112] Wilson P.J, Basit A.W. Exploiting gastrointestinal bacteria to target drugs to the colon: An in vitro study using amylose coated tablets[J]. International Journal of Pharmaceutics, 2005, 300(1-2):89-94.
[113] Cummings J.H, Milojevic S, Harding M, et al. In vivo studies of amylase and ethylcellulose coated [13C] glucose microspheres as a model for drug delivery to the colon[J]. Journal of Controlled Release, 1996, 40(1-2):123-131.
[114] Basit A.W, Podczeck F, Newton J.M, et al. The use of formulation technology to assess regional gastrointestinal drug absorption in humans[J]. European Journal of Pharmaceutical Sciences, 2004, 21(2-3):179-189.
[115] Dimantov A, Kesselman E, Shimoni E. Surface characterization and dissolution properties of high amylase corn starch-pectin coatings[J]. Food Hydrocolloids, 2004, 18(1):29-37.
[116] Kittipongpatana O. S. , Chaichanasak N. , Kanchongkittipoan S. , et al. An aqueous film-coating formulation based on sodium carboxymethyl mungbean starch[J]. Starch, 2006, 58: 587–589
[117] McConnell E.L, Tutas J, Mohamed M.A.M, et al. Colonic drug delivery using amylose films: the role of aqueous ethylcellulose dispersions in controlling drug release[J]. Cellulose, 2007, 14(1):25-34.
[118] Freire C, Podczeck F, Veiga F, et al. Starch-based coatings for colon-specific delivery. Part II: Physicochemical properties and in vitro drug release from high amylose maize starch films[J]. European Journal of Pharmaceutics and Biopharmaceutics, 2009, 72(3):587-594.
[119]李晓玺,陈玲,李琳.药物控释载体醋酸酯淀粉的消化性能研究[J].功能高分子学报, 2003, 16(4):561-564.
[120] Chen L, Li X.X, Li L, et al. Enzyme-resistant starch for oral colon-targeting drug delivery system[J]. Key Materials Engineering, 2005, 288-289:129-132.
[121] Gidley M.J, Cooke D. Molecular order and structure in enzyme-resistant retrograded starch[J]. Carbohydrate Polymers, 1995, 28(1):23-31.
[122] Gudmundsson M, Eliasson A.C. Retrogradation of amylopectin and the effects of amylose and added surfactants/emulsifiers[J]. Carbohydrate Polymers, 1990, 13(3):295-315.
[123]鲁德平,管蓉.聚合物乳液研究中的静态和动态激光光散射技术[J].胶体与聚合物, 2000, 18(2):41-43.
[124] Liu Y.G, Bo S.Q, Zhu Y.J, et al. Determination of molecular weight and molecular sizes of polymers by high temperature gel permeation chromatography with a static and dynamic laser light scattering detector[J]. Polymer, 2003, 44(23):7209-7220.
[125]刘红妮,陈曼,杨彩宁,等. GPC-MALLS技术测定PAMMO的分子量及分子量分布[J].分析测试技术与仪器, 2010, 16(1):27-31.
[126] Millard M.M, Dintzis F.R, Willett J.L, et al. Lights cattering M'w s and intrinsic viscosities of processed waxy maize starches in 90% dimethyl sulfoxide and H2O[J]. Cereal Chemistry, 1997, 74(5):687-691.
[127] Wurzburg O.B. Modified starches: properties and uses[M]. Boca Baton: CRC Press, 1986:78-96.
[128] Tamaki S, Hisamatsu M, Teranishi K. Structural change of maize starch granules by baoomill treatment[J]. Starch/St?rke, 1998, 50(8):342 -348.
[129] Jeong H.Y, Lim S.T. Crystallinity and pasting properties of freeze-thawed high amylose maize starch[J]. Starch/St?rke, 2003, 55(11):511-517.
[130] Lewandowicza G, Soral-Smietana M. Starch modification by iterated syneresis[J]. Carbohydrate Polymers, 2004, 56(4):403-413.
[131] Chu B, Hsiao B.S. Small-Angle X-ray Scattering of Polymers[J]. Chemical Reviews, 2001, 101(6):1727-1761.
[132] R?per H. Applications of starch and its derivatives[J]. Carbohydrates in Europe, 1996, 15:14-21.
[133]杨睿,周啸,罗传秋.聚合物近代仪器分析[M].北京:清华大学出版社, 2010, 6.
[134] ISO No.11357-1, Plastics: differential scanning calorimetry(DSC)[S]. Part 1: general principles, 1997.
[135]刘振海,富山立子.分析化学手册第八分册热分析[M].北京:化学工业出版社, 2000:10-14.
[136] Eerlingen R.C, Jacobs H, Delcour J.A. Enzyme-resistant starch V: Effect of retrogradation of waxy maize starch on enzyme susceptibility[J]. Cereal Chemistry, 1994, 71(4):351-355.
[137] Eerlingen R.C, Deceuninck M, Delcour J.A. Enzyme-resistant starch II: Influence of amylose chain length on resistant starch formation[J]. Cereal Chemistry, 1993, 70(3):345-350.
[138] Eerlingen R.C, Delcour J.A. Formation analysis, structure and properties of type IIIenzyme resistant starch[J]. Journal of Cereal Science, 1995, 22(2):129-138.
[139] Mutungi C, Onyango C, Jarosa D, et al. Determination of optimum conditions for enzymatic debranching of cassava starch and synthesis of resistant starch type III using central composite rotatable design[J].Starch/St?rke, 2009, 61(7):367-376.
[140] Nara S, Komiya T. Studies on the relationship between water-satured state and crystallinity by the diffraction method for moistened potato starch[J]. Starch/St?rke, 1983, 35(12):407-410.
[141]张本山,张友全,杨连生,等.淀粉多晶体系结晶度测定方法研究[J].华南理工大学学报(自然科学版), 2001, 29(5):55-58.
[142]陈福泉,张本山,卢海凤,等. X射线衍射在淀粉颗粒结晶度研究中的应用[J].食品科学, 2010, 31(3):284-287.
[143]张守文,孟庆虹,杨春华,等.玉米抗性淀粉的性质和结构研究[J].食品工业科技, 2006, 24(6):64-66.
[144] Reddy N, Yang Y.Q. Citric acid cross-linking of starch films[J]. Food Chemistry, 2010, 118(3):702-711.
[145] Wijnen P.W.J.G, Beelen T. P. M, Rummens K. P. J, et al. Silica gel from water glass: a SAXS study of the formation and ageing of fractal aggregats[J]. Journal of Applied Crystallography, 1991, 24(5):759-764.
[146] Bale H.D, Schmidt P.W. Small-angle X-ray scattering investigation of submicroscopic porosity with fractal properties[J]. Physical review letters, 1984, 53(6):596-599.
[147] Schaefer D.W, Martin J.E, Wiltzius P, et al. Fractal Geometry of Colloidal Aggregates[J]. Physical review letters, 1984, 52(26):2371-2374.
[148] Suzuki T, Chiba A, Yano T. Interpretation of small angle X-ray scattering from starch on the basis of fractals. Carbohydrate Polymers[J]. 1997, 34(3): 357-363.
[149] Vallera A.M, Cruz M.M, Ring S. The structure of amylose gels. Journal of Physics-Condensed Matter, 1994, 6(2):311-320.
[150] Viebke C, Piculell L, Nilsson S. On the Mechanism of Gelation of Helix-Forming Biopolymers[J]. Macromolecules, 1994, 27(15):4160-4166.
[151] Tan I, Wee C.C, Sopade P.A, et al. Investigation of the starch gelatinisation phenomena in water-glycerol systems: application of modulated temperature differential scanning calorimetry[J]. Carbohydrate Polymers, 2004, 58(2):191-204.
[152] Perry P.A, Donald A.M. The effect of sugars on the gelatinisation of starch[J]. Carbohydrate Polymer, 2002, 49(2):155-165.
[153] Liu H.S, Yu L, Xie F.W, et al. Gelatinization of cornstarch with different amylose/amylopectin content[J]. Carbohydrate Polymers, 2006, 65(3):357-363.
[154] Russell P.L. Gelatinisation of starches of different amylose/amylopectin content: A study by differential scanning calorimetry[J]. Journal of Cereal Science, 1987, 69(2): 133-145.
[155] Xie F., Yu, L., Su, B., et al. Rheological properties of starch with different amylose/amylopectin ratios[J]. Journal of Cereal Science, 2009, 49(3):371-377.
[156] Rao M.A. Measurement of flow and viscoelastic properties(2nd ed)[M]. New York: Springer, 2007: 62-65.
[157]徐佩弦.高聚物流变学及其应用[M].北京:化学工业出版社, 3003:21-50.
[158] Zhang Y.Y, Gu Z.B, Hong Y, et al. Pasting and rheologic properties of potato starch and maize starch mixtures[J]. Starch/St?rke, 2011, 63(1):11-16.
[159]刘冬雪,张坚樑,叶小凡,等.激光粒度分析仪在舟山邻近海域泥沙研究中的应用[J].浙江水利科技, 2009, 162(2):11-13.
[160]刘雨佳.激光粒度测量仪的应用及展望[J].航空精密制造技术, 2009, 45(5):43-45.
[161] Bohren C.F, Huffman D. Absorption and scattering of light by small particles[M]. New York: Wiley Press, 1998.
[162] Sahai D, Jackson D.S. Enthalpic transitions in native starch granules[J]. Cereal Chemistry, 1999, 76(3):444-448.
[163]张留成,翟雄伟,丁会利.高分子材料学基础[M].北京:化学工业出版社, 2002:107-113.
[164] Liu P, Yu L, Wang X.Y, et al. Glass transition temperature of starches with different amylose/amylopectin ratios[J]. Journal of Cereal Science, 2010, 51(3):388-391.
[165] Brown I.L, Mcnaught K.J, Moloney E. Hi-maize: New directions in starch technology and nutrition[J]. Food Australia, 1995, 47(6):272-275.
[166]曹心坷.聚丙烯酸树脂IV水分散体的制备以及用于微丸包衣的研究[D].沈阳:沈阳药科大学, 2005.
[167] Liu H.S, Yu L, Simon G, et al. Effects of annealing on gelatinization and microstructures of corn starches with different amylose/amylopectin ratios[J]. CarbohydratePolymers, 2009, 7(3):662-669.
[168] Chen P, Yu L, Kealy T, et al. Phase transition of starch granules observed by microscope under, shearless and shear conditions[J]. Carbohydrate Polymers, 2007, 68(3):495-501.
[169]苏得森,王思玲.物理药剂学[M].北京:化学工业出版社, 2004:267-268.
[170]潘家祯,孙晓明,朱大滨,等.挤出滚圆法制备药用微丸Ⅰ:设备的工作原理及特点[J].中国医药工业杂志, 1998, 29(8):378-380.
[171]包泳初,陈庆华,刘伟伦,等.挤出滚圆法制备药用微丸Ⅱ:制备工艺[J].中国医药工业杂志, 1999, 30(1):18-20.
[172]奚念朱.药剂学(第三版)[M].北京:人民卫生出版社, 1994:284.
[173]李汉蕴,张涛.药物制剂包衣原理工艺及设备[M].北京:中国医药科技出版社, 2006.
[174]杨燕,朱家壁,郑春丽.聚合物水分散体包衣的应用进展[J].中国医药工业杂志, 2009, 40(5):382-387.
[175] Karrout Y, Neut C, Wils D, et al. Novel polymeric film coatings for colon targeting: How to adjust desired membrane properties[J]. International Journal of Pharmaceutics, 2009, 371(1-2):64-70.
[176]孙海胜,刘秀霞,翁连华,等.薄膜包衣技术在制剂生产中的应用[J].中国药业, 2002, 11(11):25-26.
[177]中华人民共和国药典委员会编.中华人民共和国药典(2005年版)[M].北京:化学工业出版社, 2005.
[178] AOAC. Official methods of analysis of association of official analytical chemists international[M]. 17th ed. Method 991.43 Total dietary fiber. Enzymatic gravimetric method.
[179] Onyango C, Bley T, JacobA, et al. Influence of incubation temperature and time on resistant starch type III formation from autoclaved and acid-hydrolysed cassava starch[J]. Carbohydrate Polymers, 2006, 66(4):494-499.
[180] Azarmi S, Ghaffari F, Lobenberg R, et al. Mechanistic evaluation of the effect of thermal-treating on Eudragit RS matrices[J].ⅡFarmaco, 2005, 60(11-12):925-930.
[181]傅崇东,张瑜,徐惠南.增塑剂及热处理对水性包衣美沙拉秦结肠靶向微丸体外释药的影响[J].中国医药工业杂志, 2000, 31(4):149.
[182] Lippold B.H, Sutter B.K, Lippold B.C. Parameters controlling drug release from pelletscoated with aqueous ethylcellulose dispersion[J]. International journal of pharmaceutics, 1989, 54(1):15.
[183] Tan I, Wee C.C, Sopade P.A, et al. Investigation of the starch gelatinisation phenomena in water-glycerol systems:application of modulated temperature differential scanning calorimetry [J]. Carbohydrate Polymers, 2004, 58(2):191-204.
[184] Louaer W, Meniai A, Grolier J. Thermal analysis of the influence of water content on glass transitions[J]. Journal of Thermal Analysis and Calorimetry, 2008, 93(2):605-610.
[185] Wang C, Fu X, Yang L.S. Water-soluble chitosan nanoparticles as a novel carrier system for protein delivery[J]. Chinese Science Bulletin, 2007, 52:883-889.
[186]王春,孙胜玲,肖惠宁,等.水溶性壳聚糖纳米载体蛋白药物的体外释放模型[J].安徽农业科学, 2009, 37(23):10840-10842.
[187] Costa P, Souse Lobo J.M. Modeling and comparison of dissolution profiles[J]. European journal of pharmaceutical sciences, 2001, 13(2):123-133.
[188] Yin L.C, Ding J.Y, Zhang J, et al. Polymer integrity related absorption mechanism of superporous hydrogel containing interpenetrating polymer networks for oral delivery of insulin[J]. Biomaterials, 2010, 31(12):3347-3356.
[189] Dekel Y, Glucksam Y, Margalit R. Novel fibrillar insulin formulations for oral administration: Formulation and in vivo studies in diabetic mice[J]. Journal of Controlled Release, 2010, 143(1):128-135.
[190] Gonzalez C, Kanevsky D, De Marco R, et al. Non-invasive routes for insulin administration: current state and perspectives[J]. Expert Opinion Drug Delivery, 2006, 3(6):763-770.
[191]杨明功.Ⅰ糖尿病流行现状及防治对策1[J].疾病控制杂志, 2000, 4(3):193-1961.
[192] Lassmann-Vague V, Raccah D. Alternatives routes of insulin delivery[J]. Diabetes & Metabolism, 2006, 32(5):513-522.
[193] Schiffrin A. Treatment of insulin dependent diabetes with multiple subcutaneous insulin injections[J]. Medical Clinics of North America, 1982, 66(6):1251-1267.
[194] Morishita M, Peppas N.A. Is the oral route possible for peptide and protein drug delivery[J]. Drug Discovery Today, 2006, 11(19-20):905-910.
[195] Whittingham J.L, Scott D.J, Chance K, et al. Insulin at pH 2: structural analysis of the conditions promoting insulin fibre formation[J]. Journal of Molecular Biology, 2002, 318(2):479-490.
[196] Dekel Y, Glucksam Y, Elron-Gross I, et al. Insights into modeling streptozotocin-induced diabetes in ICR mice[J].Lab Anim(NY), 2009, 38(2):55-60.
[197] Calceti P, Salmaso S, Walker G, et al. Development and in vivo evaluation of an oral insulin-PEG delivery system[J]. European Journal of Pharmaceutical Sciences, 2004, 22(4):315-323.
[198] Cui F, Shi K, Zhang L, et al. Biodegradable nanoparticles loaded with insulin-phospholipid complex for oral delivery: preparation in vitro characterization and in vivo evaluation[J]. Journal of Controlled Release, 2006, 114(2):242-250.
[199] Fan Y.F, Wang Y.N, Fan Y.G, et al. Preparation of insulin nanoparticles and their encapsulation with biodegradable polyelectrolytes via the layer-by-layer adsorption[J]. International journal of pharmaceutics, 2006, 324(2):158-167.
[200] Gaucher G, Dufresne M.H, Sant V.P. Block copolymer micelles: preparation, characterization and application in drug delivery[J]. Journal of Controlled Release, 2005, 109(1-3):169-188.
[201]王玉中,张志国,孙朝辉,等.Ⅱ型糖尿病大鼠模型的建立与评价[J].毒理学杂志, 2009, 23(6):476-478.
[202] Jintapattanakit A, Junyaprasert V.B, Mao S, et al. Peroral delivery of insulin using chitosan derivatives: a comparative study of polyelectrolyte nanocomplexes and nanoparticles[J]. International Journal of Pharmaceutics, 2007, 342(1-2): 240-249.
[203] Katz A, Nambi S.S, Mather K, et al. Quantitative insulin sensitivity check index: a simple accurate method for assessing insulin sensitivity in humans[J]. J Clin Endocrinol Metab, 2000, 85(7): 2402-2410.
[204]李光伟, Bennett P.H.关于空腹血糖、空腹胰岛素乘积的倒数在流行病学研究中应用的补充说明[J].中华糖尿病杂志, 2005, 13(4): 247-249.
[205] Matthews D.R, Hosker J.P, Rudenski A.S, et al. Homeostasis model assessment: insulin resistance andβ-cell function from fasting glucose and insulin concentrations in man[J]. Diabetologia, 1985,28(7):412-419.
[206] DeFronzo R. A, Bonadonna R.C, Ferrannini E. Dathogenesis of NIDDM.A Balanced overriew[J].Diabetes Care, 1992,15(3):318-368.
[207]文香兰,李善花,金英锦,等.葡萄糖酸铬对实验性糖尿病小鼠胰岛影响的免疫组织化学观察[J].微量元素与健康研究, 2000, 17(3): 10-11.
[208] Lambkin I, Pinilla C. Targeting approaches to oral drug delivery[J]. Expert Opinion onBiological Therapy, 2002, 2(1): 67-73.
[209] Hoenig M, Jordan E.T, Ferguson D.C, et al. Oral glucose leads to a differential response in glucose, insulin, and GLP-1 in lean versus obese cats[J]. Domestic Animal Endocrinology, 2010, 38(2): 95-102.
[210]戴博斯.诊断免疫组织化学[M].北京:北京大学医学出版社,2008.
[211]倪灿荣,马大烈,戴益民.免疫组织化学实验技术及应用/生物实验室系列[M].北京:化学工业出版社,2006.
[212]金伯泉.细胞和分子免疫学实验技术[M].西安:第四军医大学出版社,2002.
[213] Russell-Jones G.J. Use of targeting agents to increase uptake and localization of drugs to the intestinal epithelium[J]. Journal of drug targeting, 2004,12(2):113-123.
[214]徐叔云,卞如濂,陈修.药理实验方法学(第2版)[M].北京:人民卫生出版社,1991:1-30.
[215]杨利芳,薛伟明,高茜,等.载胰岛素壳聚糖微球口服降血糖作用的研究[J].化学工程, 2008, 36(1):71-74.
[2] El-Malah Y, Khanfar N.M, Nazzal S. D-optimal mixture design optimization of ternary matrix blends for controlled zero-order drug release from oral dosage forms[J]. Drug Development and Industrial Pharmacy, 2006, 32(10): 1207-1218.
[3] Chidambaram N, Porter W, Flood K, et al. Formulation and characterization of new layered diffusional matrices for zero-order sustained release[J]. Journal of Controlled Release, 1998, 52(1-2): 149-158.
[4] Freiberg S, Zhu X.X. Polymer microspheres for controlled drug release[J]. International Journal of Pharmaceutics, 2004, 282(1): 1-18.
[5] Kafedjiiskik K, Krauland A. H, Hoffer M. H, et al. Synthesis and in vitro evaluation of a novel thiolated chitosan[J]. Biomaterials, 2005, 26(7): 819-826.
[6] El-Malah Y, Nazzal S. Fluid bed coating: The utility of dual programmable pumps for controlled gradient drug deposition on pellets[J]. International Journal of Pharmaceutics, 2007, 337(1-2): 361-364.
[7] Martinez-Floresa H.E, Changb Y.K, Martinez-bustosc F, et al. Effect of high fiber products on blood lipids and lipoproteins in hamsters[J]. Nutrition Research, 2004, 24(1): 85-93.
[8] Joseph R. Controlled Drug Delivery: Fundamentals and Applications[M]. Second Edition. USA. Marcel Dekker. INC, 1987: 7-9.
[9] Langer R. New methods of drug delivery[J]. Science, 1990, 249(4976): 1527-1533.
[10] Vasilevska K, Djuric Z, Jovanovic M, et al. Preparation and dissolution characteristics of controlled release diltiazem pellets[J]. Drug Development and Industrial Pharmacy, 1992, 18(15): 1649-1661.
[11]盛朝晖.口服缓控释制剂临床评价[J].中国医院药学杂志, 2005, 25(6): 558-559.
[12]张政朴.反应性与功能性高分子材料[M].北京:化学工业出版社, 2005: 26-30.
[13]杨延昆,王玉玲.药物缓释、控释制剂的研究开发现状及发展趋势[J].齐鲁药事, 2004, 23(4): 31-32.
[14] Li Y.H, Zhu J.B. Modulation of combined-release behavious from a novel tables-in-capsule system[J]. Journal of Controlled Release, 2004, 95(3): 381-382.
[15] Ramakrishna N, Mishra B. Plasticizer effect and comparative evaluation of cellulose acetate and ethylcellulose HPMC combination coatings as semipermeable membranes for oral osmotic pumps of naproxensodium[J]. Drug Development and Industrial Pharmacy, 2002, 28(4): 403-412.
[16] Yan G, Li H.N, Zhang R.H, et al. Preparation and evaluation of a sustained-release formulation of nifedipine HPMCT ablets[J]. Drug Development and Industrial Pharmacy, 2000, 26(6): 681-686.
[17] Kulkarni R.V, Mangond B.S, Mutalik S, et al. Interpenetrating polymer network microcapsules of gellan gum and egg albumin entrapped with diltiazem-resin complex for controlled release application[J]. Carbohydrate Polymers, 2011, 83(2): 1001-1007.
[18] Kumaravelrajana R, Narayananb N, Subac V, et al. Simultaneous delivery of Nifedipine and Metoprolol tartarate using sandwiched osmotic pump tablet system[J]. International Journal of Pharmaceutics, 2010, 399(1-2): 60-70.
[19] Kearney A.S. Prodrugs and targeted drug delivery[J]. Advanced Drug Delivery Reviews, 1996, 19(2): 225-239.
[20] Zhang X.R, Wang Y, Yin F.Q, et al. Study on preparation of total salvianolic acid gastricresidential tablets[J]. Chinese Traditional Patent Medicine, 2003, 25(5): 349-350.
[21] Bharaniraja B, Jayaram K, Prasad C.M, et al. Modified Katira Gum for Colon Targeted Drug Delivery[J]. Journal of Applied Polymer Science, 2011, 119(5): 2644-2651.
[22] Sangalli M. E, Maroni A, Zema L, et al. In vitro and in vito evaluation of an oral system for time and/or site-specific drug delivery[J]. Journal of Controlled Release, 2001, 73(1): 103-110.
[23] Kopecek J. Smart and genetically engineered biomaterials and drug delivery systems[J]. European journal of pharmaceutical sciences, 2003, 20(1): 1-16.
[24]陈丽华,冯怡,徐德生.中药缓控释微丸制剂的研究进展[J].中国中药杂志, 2007, 6(32): 472-475.
[25]唐星.口服缓控释制剂[M].北京:人民卫生出版社, 2007: 97-100.
[26]邓恒兵,李传枚.国内缓控释微丸制剂的研究进展[J].药学实践杂志, 2003, 3 (24): 132-135.
[27]阳长明,侯世祥,张志荣,等.缓释与控释小丸的研究进展[J].华西药学杂志, 2001, 16(2): 121.
[28]宋洪涛,郭涛,陈大为,等.多元定位释药技术制备舒胸缓释胶囊的研究[J].中草药,2005, 36(7): 993-998.
[29]张晓辉.盐酸地尔地卓缓释脉冲微丸的研制[D].河北:河北医科大学, 2006.
[30] Serraton M, Newton M, Booth S. Controlled drug release from pellets containing water insoluble drugs dissolved in a self-emulsifying system[J]. European Journal of Pharmaceutics and Biopharmaceutics, 2007, 65(1): 94-98.
[31] Marucc M, Ragnarsson I.G, Axelsson A. Evaluation of osmotic effects on coated pellets using amechanisticmodel[J]. International Journal of Pharmaceutics, 2007, 336(1): 67-74.
[32]王宪英,李焕博.薄膜包衣技术概述[J].中国药业, 1999, 8(9): 63-64.
[33] McGinity J.W. Aqueous polymeric coatings for pharmaceutical dosage forms[M]. New York: Marcel Dekker, 1997: 11-20.
[34] Frohoff-Hu¨lsman M. A. , Schmitz A. , Lippold B. C. Aqueous ethyl cellulose dispersions containing plasticizers of different water solubility and hydroxypropyl methylcellulose as coating material for diffusion pellets I. Drug release rates from coated pellets[J]. International Journal of Pharmaceutics, 1999, 177(1): 69-82.
[35]陈挺,陈庆华.聚合物水分散体包衣技术及其应用[J].中国现代应用药学, 2000,17(5): 339-343.
[36] Marcel V, Jozua L, Anton L.G. Current understanding of the deformation of latex particles during film formation[J]. Progress in organic coatings, 1997, 30(1-2): 39-49.
[37] Brondsted H. Hydrogels for site-specific oral drug delivery[J]. Biomaterial, 1995, 12(6): 548-592.
[38]张继稳,顾景凯.缓控释制剂药物动力学[M].北京:科学出版社, 2009: 27-38.
[39]黄雁,何希文,揣成智.乙基纤维素水分散体在缓控释薄膜包衣领域中的应用[J].塑料, 2007, 36(3): 37-40.
[40] Lecomte F, Siepmanna J, Waltherb M, et al. Polymer blends used for the aqueous coating of solid dosage forms: importance of the type of plasticizer[J]. Journal of Controlled Release, 2004, 99(1): 1-13.
[41]张军颖,杨梅.对薄膜包衣技术问题的探讨[J].中国医药导报, 2009, 6(7): 6-9.
[42] Shah N.H, Zhang L, Railkar A, et al. Factors affecting the kinetics and mechanism of release of glazapril from beadlets coated with aqueous and nonaqueous ethylcellulose-based coatings[J]. Pharmaceutical Technology, 1994, 18(10): 140-148.
[43] Derbin G.M, Palsson B.O, Mansfield J.F, et al. Release behavior from ethylcellulose-coated pellets: Thermomechanical and electron microbeam studies[J].Pharmaceutical Technology, 1996, 20(9): 70-80.
[44] Cole G, Hogan J, Aulton M. Pharmaceutical coating technology[M].北京:中国医药科技出版社,2000:51-61.
[45]罗明生,高天惠.药剂辅料大全[M].成都:四川科学出版社, 1993: 88-89.
[46]杜月莲.高分子材料在薄膜包衣中的应用[J].山西职工医学院学报, 2003, 13(4): 56-57.
[47] Porter S.C. Controlled-release film coatings based on ethylcellulose[J]. Drug Development and Industrial Pharmacy, 1989, 15(10): 1496-1521.
[48] Rowe R, Sheskey P.J, Weller P. Handbook of Pharmaceutical Excipients[M]. UK: Pharmaceutical Press, 2003: 237-241.
[49] Muschert S. , Siepmann F. , Leclercq B. , et al.Drug release mechanisms from ethylcellulose: PVA-PEG graft copolymer-coated pellets[J]. European Journal of Pharmaceutics and Biopharmaceutics, 2009, 72(1): 130-137.
[50] Muschert S, Siepmann F, Leclercq B, et al. Prediction of drug release from ethylcellulose coated pellets[J]. Journal of Controlled Release, 2009, 135(1): 71-79.
[51] Siepmann F, Hoffmann A, Leclercq B, et al. How to adjust desired drug release patterns from ethylcellulose-coated dosage forms[J]. Journal of Controlled Release, 2007, 119(2): 182-189.
[52] Karrout Y, Neut C, Wils D, et al. Novel polymeric film coatings for colon targeting:How to adjust desired membrane properties[J]. International Journal of Pharmaceutics, 2009, 371(1-2): 64-70.
[53]张瑜,孙茂峰.乙基纤维素水分散体包衣技术[J].中国医院药学杂志, 2002, 22(1): 49-50.
[54] Chang R.K. A review of aqueous coating techniques and preliminary data on release from a theophylline product[J]. Pharmaceutical Technology, 1987, 3(2): 56-68.
[55]傅崇东,徐惠南,张瑜. 5-氨基水杨酸结肠定位给药时控微丸的制备与体外释放[J].药学学报, 2000, 27(5): 389-393.
[56] Wesseling M, Bodmeier R. Drug release from beads coated with an aqueous colloidal ethylcellulose dispersion Aquacoat○R
[57] Gilligan C.A, Li Wan Po A. Factors affecting drug release from a pellet system coated or an organic ethylcellulose solution[J]. European Journal of Pharmaceutics and Biopharmaceutics,1999, 47(1):33-38.with an aqueous colloidal dispersion[J]. International Journal of Pharmaceutics, 1991, 73(1): 51-68.
[58] Bonacucina G, Martino P.D, Piombetti M, et al. Effect of plasticizers on properties of pregelatinised starch acetate (Amprac 01) free films[J]. International Journal of Pharmaceutics, 2006, 313(1-2): 72-77.
[59] Tarvainen M, Peltonen S, Mikkonen H, et al. Aqueous starch acetate dispersion as a novel coating material for controlled release products[J]. Journal of Controlled Release, 2004, 96(1): 179-191.
[60]陆彬.药物新剂型与新技术[M].第二版.北京:人民卫生出版社, 2005:20-26.
[61]刘欣,薛红梅,王建明,等.盐酸小檗碱结肠定位包衣片的制备工艺和体外释放研究[J].世界科技研究与发展, 2008, 30(3):347-351.
[62] Kaur K, Kim K. Studies of chitosan/organic acid/Eudragit? RS/RL-coated system for colonic delivery[J]. International Journal of Pharmaceutics, 2009, 366(1-2):140-148.
[63] Siepmann F, Siepmann J, Walther M, et al. Polymer blends for controlled release coatings[J]. Journal of Controlled Release, 2008, 125(1):1-15.
[64]韩海岭,丁宇,柴佩华,等. Eudragit L30D-55和NE30D在软胶囊肠溶包衣中的应用[J].中国医药工业杂志, 2008, 39(6):432-434
[65] Song H, Guo T, Zhang R, et al. Preparation of the traditional Chinese medicine compound recipe heart-protecting musk pH-dependent gradient-release pellets[J]. Drug Development and Industrial Pharmacy, 2002, 28(10):1261-1273.
[66]张立超,胡晋红.聚合物水分散体包衣技术的进展.药学实践杂志[J]. 1999, 17(3):144-148.
[67] CuráJ.A, Jansson P.E, Krisma C.R. Amylose is not strictly linear[J]. Starch/St? rke, 1995, 47(6):207-209.
[68] Manners D.J. Recent developments in our understanding of amylopectin structure[J]. Carbohydrate Polymers, 1989, 11(2):87-112.
[69] Biliaderis C.G. Structures and phase transitions of starch polymers[M]. In: Walter, R.H.(Ed.). Polysaccharide Association Structures in Foods. Marcel Dekker, New York: 1998: 57-168.
[70] Tester R.F, Karkalas J, Qi X. Starch-composition, fine structure and architecture[J]. Journal of Cereal Science, 2004, 39(2):151-165.
[71] Tahir R, Ellis P.R, Bogracheva T.Y, et al. Study of the structure and properties of native and hydrothermally processed wild-type, lam and r variant pea starches that affect amylolysis of these starches[J]. Biomacromolecules, 2011, 12(1):123-133.
[72] Kim H.S, Huber K.C. Physicochemical properties and amylopectin fine structures of A- and B-type granules of waxy and normal soft wheat starch[J]. Journal of Cereal Science, 2010, 51(3):256-264.
[73]二国二郎.淀粉科学手册[M].北京:中国轻工业出版社,1990:21-151.
[74] Tester R.F, Karkalas J, Qi X. Starch-composition, fine structure and architecture[J]. Journal of Cereal Science, 2004, 39(2):151-165.
[75] Muhrbeck P. On crystallinity in cereal and tuber starches[J]. Starch/St?rke, 1991, 43 (9):347-348.
[76]张燕萍.变性淀粉的制造与应用(第一版)[M].北京:化学工业出版社, 2001:70-71.
[77] AllahM A, Foda Y.H, Mahmoud R.M. X-ray diffraction of starches isolated from yellow corn, sorghum, sordan and pearlmillet[J]. Starch/St?rke, 1987, 39(2):40-42.
[78] Gernat C, Tadosta S, Damaschun G. Supra-molecular structure of legume starches revealed by X-ray scattering[J]. Starch/St?rke, 1990, 42(5):175-178.
[79]王宏志,王永利.抗性淀粉的研究[J].甘肃科技, 2010, 26(6):46-47.
[80]李晓玺,陈玲,邹芳建,等.微波改性高链玉米淀粉颗粒的抗消化性能与结晶结构的关系[J].粮食与饲料工业, 2007,(12):12-17.
[81]张华东,张淼,沈晓萍,等.微波-酶法制备RS3型玉米抗性淀粉工艺参数优化研究[J].食品科学, 2007, 28(4):237-240.
[82] Chung H.J, Jeong H.Y, Lim S.T. Effects of acid hydrolysis and defatting on crystallinity and pasting properties of freeze-thawed high amylose corn starch[J]. Carbohydrate Polymers, 2003, 54(4):449-45.
[83]陈玲,卢声宇,温其标.羧甲基化对淀粉消化性能和抗酶解性能的影响[J].华南理工大学学报, 1999, 27(6):79-84.
[84]李晓玺,温其标,陈玲.三氯氧磷交联木薯淀粉的消化性能和酶降解程度.化学工程[J]. 2002, 30(4):45-55.
[85]李晓玺,陈玲,温其标,等.醋酸酯化对淀粉生物降解性能的影响[J].现代化工, 2002, 22(S1):139-142.
[86] Seib P.A, Woo K. Food grade starch resistant to alpha-amylase and method of preparingthe same[P]. US: 5 855 946.
[87] Thompson D.B. Strategies for the manufacture of resistant starch[J]. Trends in Food Science & Technology, 2000, 11(7):245-253.
[88] Sang Y.J, Seib P.A. Resistant starches from amylose mutants of corn by simultaneous heat-moisture treatment and phosphorylation[J]. Carbohydrate Polymers, 2006, 63(2):167-175.
[89] Gonzalez-soto R.A, Mora-escobedo R, Hernandez-Sandez H. The influence of time and storage temperature on resistant starch formation from autoclaved debranched banana starch[J]. Food Research International, 2007, 40(2):304-310.
[90] Pongjanta J, Utaipattanaceep A, NaivikulO, et al. Debranching enzyme concentration effected on physicochemical properties andα-amylase hydrolysis rate of resistant starch type III from amylose rice starch[J]. Carbohydrate Polymers, 2009, 78(1):5-9.
[91] Guraya H.S, James C, Champagne T. Effect of cooling and freezing on the digestibility of debranched non-waxy and waxy starch and physical properties of the resulting material[J]. Starch/ St?rke, 2011, 53(2):64-74.
[92] Yin H, Alias L, Karim A, et al. Effect of pullulanase debranching of Sago starch at subgelatinization temperature on the yield of resistant starch[J]. Starch/ St?rke, 2007, 59(1):21-32.
[93] Vihinen M, Mantsalap. Microbial amylolytic enzymes[J]. Critical Reviews in Biochemistry and Molecular Biology, 1989, 24(4):329-418.
[94]Yao W.R, Yao H.Y. Absorbent characteristics of porous starch[J]. Starch/St?rke, 2002, 54(6):260-263.
[95] Martin E.M. Cyclodextrins and their uses: a review[J]. Process Biochemistry, 2004, 39(9):1033-1046.
[96] Shin S.I, Choi H.J, Chung K.M, et al. Slowly digestible starch from debranched waxys or ghum starch: preparation and properties[J]. Cereal Chemistry, 2004, 81(3):404-408.
[97] Nabais T, Brouillet F, Kyriacos S, et al. High-amylose carboxymethyl starch matrices for oral sustained drug-release: In vitro and in vivo evaluation[J]. European Journal of Pharmaceutics and Biopharmaceutics, 2007, 65(3):371-378.
[98] Onofre F.O, Wang Y.J. Hydroxypropylated starches of varying amylose contents as sustained release matrices in tablets[J]. International Journal of Pharmaceutics, 2010, 385(1-2):104-112.
[99] Chen L, Li X.X, Pang Y.S, et al. 1st Chinese-European Symposium on Biomaterials[J]. Suzhou, 2006.
[100] Wang X.Y, Li X.X, Chen L, et al. Preparation and characterisation of octenyl succinate starch as a delivery carrier for bioactive food components[J]. Food Chemistry, 2011, 126(3):1218-1225.
[101] Clausen A.E,Bernkop-Schnürch A. Direct compressible polymethacrylic acid-starch compositions for site-specific drug delivery[J]. Journal of Controlled Release, 2001, 75(1-2):91-102.
[102]陈立新,陈茜.淀粉作为药物载体的研究现状及应用[J].中国组织工程研究与临床康复, 2010, 14(21):3943-3944.
[103]王雪毓,何小维,黄强,等.淀粉微球的研究与开发进展[J].食品研究与开发, 2009, 30(7):155-158.
[104]沈小玲,孙庆元,蒙敏,等.一种新型兽药载体-淀粉微球的制备及其特性[J].河南农业科学, 2008(2):111-114.
[105] Yu D.M, Xiao S.Y, Tong C.Y, et al. Dialdehyde starch nanoparticles: Preparation and application in drug carrier[J]. Chinese Science Bulletin, 2007, 52(21):2913-2918.
[106] Vervoort , Van den Mooter G, Augustijins P, et al. Inulin hydrogels as carriersfor colonic drugtargeting:ⅠSynthesis and characterization of methacrylated inulin and hydrogel formation[J]. Pharmaceutical research, 1997, 14(12):1730-1737.
[107] Maris B, Verheyden L, Van Reeth K, et al. Synthesis and characterization of inulinazo hydrogels designed for colon targeting[J]. International Journal of Pharmaceutics, 2001, 213(1-2):143-152.
[108] Wang XY, Chen L, Li XX, et al. Thermal and Rheological Properties of Breadfruit Starch[J]. Journal of Food Science, 2011, 76(1): 55-61.
[109]张光华.猴面包果肉配制恒释茶碱和扑热息痛片的生物利用度[J].国外医药(植物药分册), 1990, 5(4):186-187.
[110] Milojevic S, Newton J.M, Cummings J.H, et al. Amylose as a coating for drug delivery to the colon: preparation and in vitro evaluation using 5-aminosalicylic acid pellets[J]. Journal of Controlled Release, 1996a, 38(1):75-84.
[111] Milojevic S, Newton J.M, Cummings J.H, et al. Amylose as a coating for drug delivery to the colon: preparation and in vitro evaluation using glucose pellets[J]. Journal of ControlledRelease, 1996b, 38(1):85-94.
[112] Wilson P.J, Basit A.W. Exploiting gastrointestinal bacteria to target drugs to the colon: An in vitro study using amylose coated tablets[J]. International Journal of Pharmaceutics, 2005, 300(1-2):89-94.
[113] Cummings J.H, Milojevic S, Harding M, et al. In vivo studies of amylase and ethylcellulose coated [13C] glucose microspheres as a model for drug delivery to the colon[J]. Journal of Controlled Release, 1996, 40(1-2):123-131.
[114] Basit A.W, Podczeck F, Newton J.M, et al. The use of formulation technology to assess regional gastrointestinal drug absorption in humans[J]. European Journal of Pharmaceutical Sciences, 2004, 21(2-3):179-189.
[115] Dimantov A, Kesselman E, Shimoni E. Surface characterization and dissolution properties of high amylase corn starch-pectin coatings[J]. Food Hydrocolloids, 2004, 18(1):29-37.
[116] Kittipongpatana O. S. , Chaichanasak N. , Kanchongkittipoan S. , et al. An aqueous film-coating formulation based on sodium carboxymethyl mungbean starch[J]. Starch, 2006, 58: 587–589
[117] McConnell E.L, Tutas J, Mohamed M.A.M, et al. Colonic drug delivery using amylose films: the role of aqueous ethylcellulose dispersions in controlling drug release[J]. Cellulose, 2007, 14(1):25-34.
[118] Freire C, Podczeck F, Veiga F, et al. Starch-based coatings for colon-specific delivery. Part II: Physicochemical properties and in vitro drug release from high amylose maize starch films[J]. European Journal of Pharmaceutics and Biopharmaceutics, 2009, 72(3):587-594.
[119]李晓玺,陈玲,李琳.药物控释载体醋酸酯淀粉的消化性能研究[J].功能高分子学报, 2003, 16(4):561-564.
[120] Chen L, Li X.X, Li L, et al. Enzyme-resistant starch for oral colon-targeting drug delivery system[J]. Key Materials Engineering, 2005, 288-289:129-132.
[121] Gidley M.J, Cooke D. Molecular order and structure in enzyme-resistant retrograded starch[J]. Carbohydrate Polymers, 1995, 28(1):23-31.
[122] Gudmundsson M, Eliasson A.C. Retrogradation of amylopectin and the effects of amylose and added surfactants/emulsifiers[J]. Carbohydrate Polymers, 1990, 13(3):295-315.
[123]鲁德平,管蓉.聚合物乳液研究中的静态和动态激光光散射技术[J].胶体与聚合物, 2000, 18(2):41-43.
[124] Liu Y.G, Bo S.Q, Zhu Y.J, et al. Determination of molecular weight and molecular sizes of polymers by high temperature gel permeation chromatography with a static and dynamic laser light scattering detector[J]. Polymer, 2003, 44(23):7209-7220.
[125]刘红妮,陈曼,杨彩宁,等. GPC-MALLS技术测定PAMMO的分子量及分子量分布[J].分析测试技术与仪器, 2010, 16(1):27-31.
[126] Millard M.M, Dintzis F.R, Willett J.L, et al. Lights cattering M'w s and intrinsic viscosities of processed waxy maize starches in 90% dimethyl sulfoxide and H2O[J]. Cereal Chemistry, 1997, 74(5):687-691.
[127] Wurzburg O.B. Modified starches: properties and uses[M]. Boca Baton: CRC Press, 1986:78-96.
[128] Tamaki S, Hisamatsu M, Teranishi K. Structural change of maize starch granules by baoomill treatment[J]. Starch/St?rke, 1998, 50(8):342 -348.
[129] Jeong H.Y, Lim S.T. Crystallinity and pasting properties of freeze-thawed high amylose maize starch[J]. Starch/St?rke, 2003, 55(11):511-517.
[130] Lewandowicza G, Soral-Smietana M. Starch modification by iterated syneresis[J]. Carbohydrate Polymers, 2004, 56(4):403-413.
[131] Chu B, Hsiao B.S. Small-Angle X-ray Scattering of Polymers[J]. Chemical Reviews, 2001, 101(6):1727-1761.
[132] R?per H. Applications of starch and its derivatives[J]. Carbohydrates in Europe, 1996, 15:14-21.
[133]杨睿,周啸,罗传秋.聚合物近代仪器分析[M].北京:清华大学出版社, 2010, 6.
[134] ISO No.11357-1, Plastics: differential scanning calorimetry(DSC)[S]. Part 1: general principles, 1997.
[135]刘振海,富山立子.分析化学手册第八分册热分析[M].北京:化学工业出版社, 2000:10-14.
[136] Eerlingen R.C, Jacobs H, Delcour J.A. Enzyme-resistant starch V: Effect of retrogradation of waxy maize starch on enzyme susceptibility[J]. Cereal Chemistry, 1994, 71(4):351-355.
[137] Eerlingen R.C, Deceuninck M, Delcour J.A. Enzyme-resistant starch II: Influence of amylose chain length on resistant starch formation[J]. Cereal Chemistry, 1993, 70(3):345-350.
[138] Eerlingen R.C, Delcour J.A. Formation analysis, structure and properties of type IIIenzyme resistant starch[J]. Journal of Cereal Science, 1995, 22(2):129-138.
[139] Mutungi C, Onyango C, Jarosa D, et al. Determination of optimum conditions for enzymatic debranching of cassava starch and synthesis of resistant starch type III using central composite rotatable design[J].Starch/St?rke, 2009, 61(7):367-376.
[140] Nara S, Komiya T. Studies on the relationship between water-satured state and crystallinity by the diffraction method for moistened potato starch[J]. Starch/St?rke, 1983, 35(12):407-410.
[141]张本山,张友全,杨连生,等.淀粉多晶体系结晶度测定方法研究[J].华南理工大学学报(自然科学版), 2001, 29(5):55-58.
[142]陈福泉,张本山,卢海凤,等. X射线衍射在淀粉颗粒结晶度研究中的应用[J].食品科学, 2010, 31(3):284-287.
[143]张守文,孟庆虹,杨春华,等.玉米抗性淀粉的性质和结构研究[J].食品工业科技, 2006, 24(6):64-66.
[144] Reddy N, Yang Y.Q. Citric acid cross-linking of starch films[J]. Food Chemistry, 2010, 118(3):702-711.
[145] Wijnen P.W.J.G, Beelen T. P. M, Rummens K. P. J, et al. Silica gel from water glass: a SAXS study of the formation and ageing of fractal aggregats[J]. Journal of Applied Crystallography, 1991, 24(5):759-764.
[146] Bale H.D, Schmidt P.W. Small-angle X-ray scattering investigation of submicroscopic porosity with fractal properties[J]. Physical review letters, 1984, 53(6):596-599.
[147] Schaefer D.W, Martin J.E, Wiltzius P, et al. Fractal Geometry of Colloidal Aggregates[J]. Physical review letters, 1984, 52(26):2371-2374.
[148] Suzuki T, Chiba A, Yano T. Interpretation of small angle X-ray scattering from starch on the basis of fractals. Carbohydrate Polymers[J]. 1997, 34(3): 357-363.
[149] Vallera A.M, Cruz M.M, Ring S. The structure of amylose gels. Journal of Physics-Condensed Matter, 1994, 6(2):311-320.
[150] Viebke C, Piculell L, Nilsson S. On the Mechanism of Gelation of Helix-Forming Biopolymers[J]. Macromolecules, 1994, 27(15):4160-4166.
[151] Tan I, Wee C.C, Sopade P.A, et al. Investigation of the starch gelatinisation phenomena in water-glycerol systems: application of modulated temperature differential scanning calorimetry[J]. Carbohydrate Polymers, 2004, 58(2):191-204.
[152] Perry P.A, Donald A.M. The effect of sugars on the gelatinisation of starch[J]. Carbohydrate Polymer, 2002, 49(2):155-165.
[153] Liu H.S, Yu L, Xie F.W, et al. Gelatinization of cornstarch with different amylose/amylopectin content[J]. Carbohydrate Polymers, 2006, 65(3):357-363.
[154] Russell P.L. Gelatinisation of starches of different amylose/amylopectin content: A study by differential scanning calorimetry[J]. Journal of Cereal Science, 1987, 69(2): 133-145.
[155] Xie F., Yu, L., Su, B., et al. Rheological properties of starch with different amylose/amylopectin ratios[J]. Journal of Cereal Science, 2009, 49(3):371-377.
[156] Rao M.A. Measurement of flow and viscoelastic properties(2nd ed)[M]. New York: Springer, 2007: 62-65.
[157]徐佩弦.高聚物流变学及其应用[M].北京:化学工业出版社, 3003:21-50.
[158] Zhang Y.Y, Gu Z.B, Hong Y, et al. Pasting and rheologic properties of potato starch and maize starch mixtures[J]. Starch/St?rke, 2011, 63(1):11-16.
[159]刘冬雪,张坚樑,叶小凡,等.激光粒度分析仪在舟山邻近海域泥沙研究中的应用[J].浙江水利科技, 2009, 162(2):11-13.
[160]刘雨佳.激光粒度测量仪的应用及展望[J].航空精密制造技术, 2009, 45(5):43-45.
[161] Bohren C.F, Huffman D. Absorption and scattering of light by small particles[M]. New York: Wiley Press, 1998.
[162] Sahai D, Jackson D.S. Enthalpic transitions in native starch granules[J]. Cereal Chemistry, 1999, 76(3):444-448.
[163]张留成,翟雄伟,丁会利.高分子材料学基础[M].北京:化学工业出版社, 2002:107-113.
[164] Liu P, Yu L, Wang X.Y, et al. Glass transition temperature of starches with different amylose/amylopectin ratios[J]. Journal of Cereal Science, 2010, 51(3):388-391.
[165] Brown I.L, Mcnaught K.J, Moloney E. Hi-maize: New directions in starch technology and nutrition[J]. Food Australia, 1995, 47(6):272-275.
[166]曹心坷.聚丙烯酸树脂IV水分散体的制备以及用于微丸包衣的研究[D].沈阳:沈阳药科大学, 2005.
[167] Liu H.S, Yu L, Simon G, et al. Effects of annealing on gelatinization and microstructures of corn starches with different amylose/amylopectin ratios[J]. CarbohydratePolymers, 2009, 7(3):662-669.
[168] Chen P, Yu L, Kealy T, et al. Phase transition of starch granules observed by microscope under, shearless and shear conditions[J]. Carbohydrate Polymers, 2007, 68(3):495-501.
[169]苏得森,王思玲.物理药剂学[M].北京:化学工业出版社, 2004:267-268.
[170]潘家祯,孙晓明,朱大滨,等.挤出滚圆法制备药用微丸Ⅰ:设备的工作原理及特点[J].中国医药工业杂志, 1998, 29(8):378-380.
[171]包泳初,陈庆华,刘伟伦,等.挤出滚圆法制备药用微丸Ⅱ:制备工艺[J].中国医药工业杂志, 1999, 30(1):18-20.
[172]奚念朱.药剂学(第三版)[M].北京:人民卫生出版社, 1994:284.
[173]李汉蕴,张涛.药物制剂包衣原理工艺及设备[M].北京:中国医药科技出版社, 2006.
[174]杨燕,朱家壁,郑春丽.聚合物水分散体包衣的应用进展[J].中国医药工业杂志, 2009, 40(5):382-387.
[175] Karrout Y, Neut C, Wils D, et al. Novel polymeric film coatings for colon targeting: How to adjust desired membrane properties[J]. International Journal of Pharmaceutics, 2009, 371(1-2):64-70.
[176]孙海胜,刘秀霞,翁连华,等.薄膜包衣技术在制剂生产中的应用[J].中国药业, 2002, 11(11):25-26.
[177]中华人民共和国药典委员会编.中华人民共和国药典(2005年版)[M].北京:化学工业出版社, 2005.
[178] AOAC. Official methods of analysis of association of official analytical chemists international[M]. 17th ed. Method 991.43 Total dietary fiber. Enzymatic gravimetric method.
[179] Onyango C, Bley T, JacobA, et al. Influence of incubation temperature and time on resistant starch type III formation from autoclaved and acid-hydrolysed cassava starch[J]. Carbohydrate Polymers, 2006, 66(4):494-499.
[180] Azarmi S, Ghaffari F, Lobenberg R, et al. Mechanistic evaluation of the effect of thermal-treating on Eudragit RS matrices[J].ⅡFarmaco, 2005, 60(11-12):925-930.
[181]傅崇东,张瑜,徐惠南.增塑剂及热处理对水性包衣美沙拉秦结肠靶向微丸体外释药的影响[J].中国医药工业杂志, 2000, 31(4):149.
[182] Lippold B.H, Sutter B.K, Lippold B.C. Parameters controlling drug release from pelletscoated with aqueous ethylcellulose dispersion[J]. International journal of pharmaceutics, 1989, 54(1):15.
[183] Tan I, Wee C.C, Sopade P.A, et al. Investigation of the starch gelatinisation phenomena in water-glycerol systems:application of modulated temperature differential scanning calorimetry [J]. Carbohydrate Polymers, 2004, 58(2):191-204.
[184] Louaer W, Meniai A, Grolier J. Thermal analysis of the influence of water content on glass transitions[J]. Journal of Thermal Analysis and Calorimetry, 2008, 93(2):605-610.
[185] Wang C, Fu X, Yang L.S. Water-soluble chitosan nanoparticles as a novel carrier system for protein delivery[J]. Chinese Science Bulletin, 2007, 52:883-889.
[186]王春,孙胜玲,肖惠宁,等.水溶性壳聚糖纳米载体蛋白药物的体外释放模型[J].安徽农业科学, 2009, 37(23):10840-10842.
[187] Costa P, Souse Lobo J.M. Modeling and comparison of dissolution profiles[J]. European journal of pharmaceutical sciences, 2001, 13(2):123-133.
[188] Yin L.C, Ding J.Y, Zhang J, et al. Polymer integrity related absorption mechanism of superporous hydrogel containing interpenetrating polymer networks for oral delivery of insulin[J]. Biomaterials, 2010, 31(12):3347-3356.
[189] Dekel Y, Glucksam Y, Margalit R. Novel fibrillar insulin formulations for oral administration: Formulation and in vivo studies in diabetic mice[J]. Journal of Controlled Release, 2010, 143(1):128-135.
[190] Gonzalez C, Kanevsky D, De Marco R, et al. Non-invasive routes for insulin administration: current state and perspectives[J]. Expert Opinion Drug Delivery, 2006, 3(6):763-770.
[191]杨明功.Ⅰ糖尿病流行现状及防治对策1[J].疾病控制杂志, 2000, 4(3):193-1961.
[192] Lassmann-Vague V, Raccah D. Alternatives routes of insulin delivery[J]. Diabetes & Metabolism, 2006, 32(5):513-522.
[193] Schiffrin A. Treatment of insulin dependent diabetes with multiple subcutaneous insulin injections[J]. Medical Clinics of North America, 1982, 66(6):1251-1267.
[194] Morishita M, Peppas N.A. Is the oral route possible for peptide and protein drug delivery[J]. Drug Discovery Today, 2006, 11(19-20):905-910.
[195] Whittingham J.L, Scott D.J, Chance K, et al. Insulin at pH 2: structural analysis of the conditions promoting insulin fibre formation[J]. Journal of Molecular Biology, 2002, 318(2):479-490.
[196] Dekel Y, Glucksam Y, Elron-Gross I, et al. Insights into modeling streptozotocin-induced diabetes in ICR mice[J].Lab Anim(NY), 2009, 38(2):55-60.
[197] Calceti P, Salmaso S, Walker G, et al. Development and in vivo evaluation of an oral insulin-PEG delivery system[J]. European Journal of Pharmaceutical Sciences, 2004, 22(4):315-323.
[198] Cui F, Shi K, Zhang L, et al. Biodegradable nanoparticles loaded with insulin-phospholipid complex for oral delivery: preparation in vitro characterization and in vivo evaluation[J]. Journal of Controlled Release, 2006, 114(2):242-250.
[199] Fan Y.F, Wang Y.N, Fan Y.G, et al. Preparation of insulin nanoparticles and their encapsulation with biodegradable polyelectrolytes via the layer-by-layer adsorption[J]. International journal of pharmaceutics, 2006, 324(2):158-167.
[200] Gaucher G, Dufresne M.H, Sant V.P. Block copolymer micelles: preparation, characterization and application in drug delivery[J]. Journal of Controlled Release, 2005, 109(1-3):169-188.
[201]王玉中,张志国,孙朝辉,等.Ⅱ型糖尿病大鼠模型的建立与评价[J].毒理学杂志, 2009, 23(6):476-478.
[202] Jintapattanakit A, Junyaprasert V.B, Mao S, et al. Peroral delivery of insulin using chitosan derivatives: a comparative study of polyelectrolyte nanocomplexes and nanoparticles[J]. International Journal of Pharmaceutics, 2007, 342(1-2): 240-249.
[203] Katz A, Nambi S.S, Mather K, et al. Quantitative insulin sensitivity check index: a simple accurate method for assessing insulin sensitivity in humans[J]. J Clin Endocrinol Metab, 2000, 85(7): 2402-2410.
[204]李光伟, Bennett P.H.关于空腹血糖、空腹胰岛素乘积的倒数在流行病学研究中应用的补充说明[J].中华糖尿病杂志, 2005, 13(4): 247-249.
[205] Matthews D.R, Hosker J.P, Rudenski A.S, et al. Homeostasis model assessment: insulin resistance andβ-cell function from fasting glucose and insulin concentrations in man[J]. Diabetologia, 1985,28(7):412-419.
[206] DeFronzo R. A, Bonadonna R.C, Ferrannini E. Dathogenesis of NIDDM.A Balanced overriew[J].Diabetes Care, 1992,15(3):318-368.
[207]文香兰,李善花,金英锦,等.葡萄糖酸铬对实验性糖尿病小鼠胰岛影响的免疫组织化学观察[J].微量元素与健康研究, 2000, 17(3): 10-11.
[208] Lambkin I, Pinilla C. Targeting approaches to oral drug delivery[J]. Expert Opinion onBiological Therapy, 2002, 2(1): 67-73.
[209] Hoenig M, Jordan E.T, Ferguson D.C, et al. Oral glucose leads to a differential response in glucose, insulin, and GLP-1 in lean versus obese cats[J]. Domestic Animal Endocrinology, 2010, 38(2): 95-102.
[210]戴博斯.诊断免疫组织化学[M].北京:北京大学医学出版社,2008.
[211]倪灿荣,马大烈,戴益民.免疫组织化学实验技术及应用/生物实验室系列[M].北京:化学工业出版社,2006.
[212]金伯泉.细胞和分子免疫学实验技术[M].西安:第四军医大学出版社,2002.
[213] Russell-Jones G.J. Use of targeting agents to increase uptake and localization of drugs to the intestinal epithelium[J]. Journal of drug targeting, 2004,12(2):113-123.
[214]徐叔云,卞如濂,陈修.药理实验方法学(第2版)[M].北京:人民卫生出版社,1991:1-30.
[215]杨利芳,薛伟明,高茜,等.载胰岛素壳聚糖微球口服降血糖作用的研究[J].化学工程, 2008, 36(1):71-74.