维生素A和维生素E纳米球/微球双包埋体系的研究
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摘要
维生素A是人体正常生长发育、骨骼形成、维持正常视觉及免疫系统的必需营养元素,具有抗脂质过氧化,增强免疫,增强抗感染,改善缺铁性贫血等功能。维生素E是脂溶性天然抗氧化剂,还能提高免疫力、抗癌、预防心血管疾病。但是维生素A和维生素E均不溶于水,生物利用度低,极大的限制了其应用。以纳米球/微球双包埋体系作为输送系统是改善脂溶性维生素的水溶性,提高生物利用度并提供可控分步释放的有效途径。
本论文研究了维生素A、维生素E纳米球/微球双包埋体系的制备工艺和配方,在模拟胃肠液中的释放规律以及贮存稳定性,进一步研究了维生素A、维生素E纳米球/微球双包埋体系以及壁材的性质,为贮藏稳定性和释放提供理论依据。
首先采用热均质法制备了维生素A纳米球悬浮液,以单甘酯为壁材的纳米球悬浮液的最佳配方为Tween-80:芯材维生素A:单甘酯:辛烯基琥珀酸酯化淀粉为1:1.25:5:40(w/w),所得包埋效率为93.9%,包埋产率为70.47%,纳米球的平均粒径为229.4nm。以黄蜂蜡为壁材的纳米球悬浮液的最佳配方为Tween-80:维生素A:蜂蜡:辛烯基琥珀酸酯化淀粉为1:2:10:50(w/w),所得包埋效率为93.41%,包埋产率为73.46%,纳米球的平均粒径为335nm。然后采用热均质-喷雾干燥法制备了维生素A、维生素E纳米球/微球双包埋体系。优化微球的最佳芯壁比为50%(w/w),最佳喷雾工艺条件为固形物含量40%,进风温度185℃,出风温度80℃,均质压力40Mpa。以单甘酯为纳米球壁材的维生素A、维生素E纳米球/微球双包埋产品对维生素A、维生素E的包埋效率分别达到92.97%和95.11%;以黄蜂蜡为纳米球壁材的维生素A、维生素E纳米球/微球双包埋产品对维生素A和维生素E的包埋效率分别达到90.96%和91.38%。
研究了维生素A、维生素E纳米球/微球双包埋体系在模拟胃液、模拟肠液中的释放。结果发现以蜂蜡作为纳米球壁材的双包埋体系的缓释性能要优于以单甘酯作为纳米球壁材的双包埋体系。两者在模拟胃液和肠液中均体现一定的缓释效果,由于胰酶对维生素A、维生素E纳米球/微球双包埋体系的内外层壁材均有作用,所以体系在添加了胰酶的肠液中释放速率较快。
研究了氧气、光照、温度、湿度对维生素A、维生素E纳米球/微球双包埋体系贮藏稳定性的影响。结果发现在4℃下避光贮藏100天,维生素A、维生素E纳米球/微球双包埋产品对维生素A、维生素E的保留率分别达到76%、60%以上,外观品质也没有变化。高温和高湿的环境对双包埋的外观和保留率均有很大的影响。
SEM显微图片显示维生素A、维生素E纳米球/微球产品的表面未见缝隙和裂缝,并且光滑致密,有较高的包埋效率。通过比较以蜂蜡和单甘酯作为纳米球壁材的双包埋体系,包埋维生素E和以蜂蜡为壁材的纳米球的微球表面更为光滑致密。
差式扫描量热分析了产品的玻璃化转变温度,以单甘酯为纳米球壁材的维生素A、维生素E的纳米球/微球双包埋体系的玻璃化转变温度为49.265℃,玻璃化转变热焓为0.39J·g-1·℃-1。以蜂蜡为纳米球壁材的维生素A、维生素E的纳米球/微球双包埋体系的玻璃化转变温度为47.51℃,玻璃化转变热焓为3.04J·g-1·℃-1。玻璃化转变温度高于通常的贮藏温度(25℃),预示双包埋体系的产品在常温下贮藏时处于玻璃态,其贮藏稳定性良好。
采用热重分析研究表明,以蜂蜡为纳米球壁材的双包埋产品热稳定性略好于以单甘酯为纳米球壁材的双包埋产品,贮存了3个月之后,失重变化主要是由水分造成的,说明产品有少量吸湿。
由不同纳米球壁材制成的双包埋产品以及壁材进行X-射线衍射和DSC分析的结果表明,在脂质重结晶时,单甘酯比蜂蜡更倾向于形成过冷熔融状态,这对于提高包埋效率是有利的,但晶型转变导致纳米球的芯材排出,因而贮存稳定性差。蜂蜡容易形成较为稳定的正交晶(β’型),在贮存时物理稳定性较好。
Vitamin A is essential nutrition element for the maintenance of healthy body development, healthy skeletal, healthy vision and integrity of the immune system. It has functions as lipids antipreoxidation, enhance immunity and the ability of resisting infection, improve anemia arise from lack of iron. Vitamin E is natural lipophilic antioxidant. It can enhance immunity, has anti-cancer function, prevent heart and blood vessel diseases. However the application of these nutrients has been restricted due to their low aqueous solubility and bioavailability. Nanosphere/microsphere double-layers encapsulation delivery system is a possible route that is helpful to solve the aforementioned problems such as improve aqueous solubility, enhance bioavailability and provide multi-steps release.
The preparation method and formulation of vitamins A and E nanosphere/microsphere double-layers encapsulation system were developed. The storage stability of vitamins A and E nanosphere/microsphere double-layers encapsulation system and the release rate of vitamins A and E nanosphere/microsphere double-layers encapsulation system in artificial simulation gastric and intestinal juices was determined.
Vitamin A nanospheres suspension was prepared by hot homogenization which has emerged as a reliable technique. The results showed that the best formulation of nanosuspension with glycerin monostearate as wall material of nanosphere was the proportion between Tween-80, glycerin monostearate, vtiamin A and starch octenylsuccinate was 1:1.25:5:40 (w/w), the encapsulation efficiency (EE) of vitamin A nanospheres was 93.9%, the product yield was 70.47%, the average particle size (DZ) was 229.4nm. the best formulation of nanosuspension with beeswax as wall material of nanosphere was the proportion between beeswax and starch octenylsuccinate was 1:5 (w/w); the proportion between Tween-80, vtiamin A, beeswax and starch octenylsuccinate was 1:2:10:50(w/w), the encapsulation efficiency (EE) of vitamin A nanospheres was 93.41%, the product yield was 73.46%, the average particle size (DZ) was 335nm. The vitamins A and E nanosphere/microsphere double-layers encapsulation system was prepared by hot homogenization -spray drying technique. the proportion between vitamin E、nanospheres and wall material of microsphere starch octenylsuccinate was 1:2 (w/w), the optimum spray drying parameters were as follows: solid content was 40% (w/w), the inlet air temperature was around 185℃,the outlet air temperature was around 80℃, the homogenizing pressure was 40 MPa. the encapsulation efficiency of vitamins A and E and in the nanosphere/microsphere double-layers encapsulation system with glycerin monostearate as wall material of nanospheres was 92.97% and 93.9%; the encapsulation efficiency of vitamins A and E and in the nanosphere/microsphere double-layers encapsulation system with beeswax as wall material of nanospheres was 90.96% and 91.38%.
The release study of vitamins A and E nanosphere/microsphere double-layers encapsulation system in artificial simulation gastric and intestinal juices showed that the release profile of the system when the beeswax as the wall material of nanopaticles was better than the system when the glycerin monostearate as the wall material of nanopaticles. Both of them exhibited a prolonged release profile. Pancreatin functions towards wall materials of both of nanospheres and microspheres. Vitamins A and E release faster in the intestinal juices with pancreatin.
The storage stability of vitamins A and E nanosphere/microsphere double-layers encapsulation system was studied under different storing condition, the influence upon retention ratio from oxygen, light, temperature and humidity. The results show that retention ratio of vitamins A and E were 76% and 60% respectively with no change in appearance under condition of 4℃, light and oxygen avoiding, stored 100 days. The high temperature and high moisture have a great effect on the storage stability of products.
SEM micrographs showed that vitamins A and E nanosphere/microsphere double-layers encapsulation product presented a smooth and compact surface without crack and broken microspheres which indicate the high encapsulation efficiency. The product with beeswax as wall material of nanospheres showed a smoother surface by comparation. Glass transition temperature (Tg) of vitamins A and E nanosphere/microsphere double-layers encapsulation product with glycerin monostearate as wall material of nanospheres by differential scanning calorimetry (DSC) was at 49.265℃with⊿Cp of 0.39J·g-1·℃-1; glass transition temperature of vitamins A and E nanosphere/microsphere double-layers encapsulation product with beeswax as wall material of nanospheres was at 47.51℃w ith⊿C p of 3.04J·g-1·℃-1which indicated the storage stability was good because both of the encapsulation products were at the glass state in normal temperature storage(25℃) .
Thermogravimereic analysis(TGA) showed the thermal stability of the encapsulation product with different nanospheres wall material before and after stored 3 months. The encapsulation product with beeswax as nanospheres wall material showed better thermal stability. The moisture absorption of encapsulation product cause the change of thermogravimetry after 3 months.
The results of X-ray diffraction and DSC analysis towards vitamins A and E nanosphere/microsphere double-layers encapsulation product and wall material indicated that glycerin monostearate intended to be supercooled melt which is in favor of encapsulation during recrystallization. But the vitamins would be expelled during modification of lopid thought storage. Beeswax displayed orthorhombic subcell packing(β’polymorph) which made the encapsulation product good physical stability during storage.
本论文研究了维生素A、维生素E纳米球/微球双包埋体系的制备工艺和配方,在模拟胃肠液中的释放规律以及贮存稳定性,进一步研究了维生素A、维生素E纳米球/微球双包埋体系以及壁材的性质,为贮藏稳定性和释放提供理论依据。
首先采用热均质法制备了维生素A纳米球悬浮液,以单甘酯为壁材的纳米球悬浮液的最佳配方为Tween-80:芯材维生素A:单甘酯:辛烯基琥珀酸酯化淀粉为1:1.25:5:40(w/w),所得包埋效率为93.9%,包埋产率为70.47%,纳米球的平均粒径为229.4nm。以黄蜂蜡为壁材的纳米球悬浮液的最佳配方为Tween-80:维生素A:蜂蜡:辛烯基琥珀酸酯化淀粉为1:2:10:50(w/w),所得包埋效率为93.41%,包埋产率为73.46%,纳米球的平均粒径为335nm。然后采用热均质-喷雾干燥法制备了维生素A、维生素E纳米球/微球双包埋体系。优化微球的最佳芯壁比为50%(w/w),最佳喷雾工艺条件为固形物含量40%,进风温度185℃,出风温度80℃,均质压力40Mpa。以单甘酯为纳米球壁材的维生素A、维生素E纳米球/微球双包埋产品对维生素A、维生素E的包埋效率分别达到92.97%和95.11%;以黄蜂蜡为纳米球壁材的维生素A、维生素E纳米球/微球双包埋产品对维生素A和维生素E的包埋效率分别达到90.96%和91.38%。
研究了维生素A、维生素E纳米球/微球双包埋体系在模拟胃液、模拟肠液中的释放。结果发现以蜂蜡作为纳米球壁材的双包埋体系的缓释性能要优于以单甘酯作为纳米球壁材的双包埋体系。两者在模拟胃液和肠液中均体现一定的缓释效果,由于胰酶对维生素A、维生素E纳米球/微球双包埋体系的内外层壁材均有作用,所以体系在添加了胰酶的肠液中释放速率较快。
研究了氧气、光照、温度、湿度对维生素A、维生素E纳米球/微球双包埋体系贮藏稳定性的影响。结果发现在4℃下避光贮藏100天,维生素A、维生素E纳米球/微球双包埋产品对维生素A、维生素E的保留率分别达到76%、60%以上,外观品质也没有变化。高温和高湿的环境对双包埋的外观和保留率均有很大的影响。
SEM显微图片显示维生素A、维生素E纳米球/微球产品的表面未见缝隙和裂缝,并且光滑致密,有较高的包埋效率。通过比较以蜂蜡和单甘酯作为纳米球壁材的双包埋体系,包埋维生素E和以蜂蜡为壁材的纳米球的微球表面更为光滑致密。
差式扫描量热分析了产品的玻璃化转变温度,以单甘酯为纳米球壁材的维生素A、维生素E的纳米球/微球双包埋体系的玻璃化转变温度为49.265℃,玻璃化转变热焓为0.39J·g-1·℃-1。以蜂蜡为纳米球壁材的维生素A、维生素E的纳米球/微球双包埋体系的玻璃化转变温度为47.51℃,玻璃化转变热焓为3.04J·g-1·℃-1。玻璃化转变温度高于通常的贮藏温度(25℃),预示双包埋体系的产品在常温下贮藏时处于玻璃态,其贮藏稳定性良好。
采用热重分析研究表明,以蜂蜡为纳米球壁材的双包埋产品热稳定性略好于以单甘酯为纳米球壁材的双包埋产品,贮存了3个月之后,失重变化主要是由水分造成的,说明产品有少量吸湿。
由不同纳米球壁材制成的双包埋产品以及壁材进行X-射线衍射和DSC分析的结果表明,在脂质重结晶时,单甘酯比蜂蜡更倾向于形成过冷熔融状态,这对于提高包埋效率是有利的,但晶型转变导致纳米球的芯材排出,因而贮存稳定性差。蜂蜡容易形成较为稳定的正交晶(β’型),在贮存时物理稳定性较好。
Vitamin A is essential nutrition element for the maintenance of healthy body development, healthy skeletal, healthy vision and integrity of the immune system. It has functions as lipids antipreoxidation, enhance immunity and the ability of resisting infection, improve anemia arise from lack of iron. Vitamin E is natural lipophilic antioxidant. It can enhance immunity, has anti-cancer function, prevent heart and blood vessel diseases. However the application of these nutrients has been restricted due to their low aqueous solubility and bioavailability. Nanosphere/microsphere double-layers encapsulation delivery system is a possible route that is helpful to solve the aforementioned problems such as improve aqueous solubility, enhance bioavailability and provide multi-steps release.
The preparation method and formulation of vitamins A and E nanosphere/microsphere double-layers encapsulation system were developed. The storage stability of vitamins A and E nanosphere/microsphere double-layers encapsulation system and the release rate of vitamins A and E nanosphere/microsphere double-layers encapsulation system in artificial simulation gastric and intestinal juices was determined.
Vitamin A nanospheres suspension was prepared by hot homogenization which has emerged as a reliable technique. The results showed that the best formulation of nanosuspension with glycerin monostearate as wall material of nanosphere was the proportion between Tween-80, glycerin monostearate, vtiamin A and starch octenylsuccinate was 1:1.25:5:40 (w/w), the encapsulation efficiency (EE) of vitamin A nanospheres was 93.9%, the product yield was 70.47%, the average particle size (DZ) was 229.4nm. the best formulation of nanosuspension with beeswax as wall material of nanosphere was the proportion between beeswax and starch octenylsuccinate was 1:5 (w/w); the proportion between Tween-80, vtiamin A, beeswax and starch octenylsuccinate was 1:2:10:50(w/w), the encapsulation efficiency (EE) of vitamin A nanospheres was 93.41%, the product yield was 73.46%, the average particle size (DZ) was 335nm. The vitamins A and E nanosphere/microsphere double-layers encapsulation system was prepared by hot homogenization -spray drying technique. the proportion between vitamin E、nanospheres and wall material of microsphere starch octenylsuccinate was 1:2 (w/w), the optimum spray drying parameters were as follows: solid content was 40% (w/w), the inlet air temperature was around 185℃,the outlet air temperature was around 80℃, the homogenizing pressure was 40 MPa. the encapsulation efficiency of vitamins A and E and in the nanosphere/microsphere double-layers encapsulation system with glycerin monostearate as wall material of nanospheres was 92.97% and 93.9%; the encapsulation efficiency of vitamins A and E and in the nanosphere/microsphere double-layers encapsulation system with beeswax as wall material of nanospheres was 90.96% and 91.38%.
The release study of vitamins A and E nanosphere/microsphere double-layers encapsulation system in artificial simulation gastric and intestinal juices showed that the release profile of the system when the beeswax as the wall material of nanopaticles was better than the system when the glycerin monostearate as the wall material of nanopaticles. Both of them exhibited a prolonged release profile. Pancreatin functions towards wall materials of both of nanospheres and microspheres. Vitamins A and E release faster in the intestinal juices with pancreatin.
The storage stability of vitamins A and E nanosphere/microsphere double-layers encapsulation system was studied under different storing condition, the influence upon retention ratio from oxygen, light, temperature and humidity. The results show that retention ratio of vitamins A and E were 76% and 60% respectively with no change in appearance under condition of 4℃, light and oxygen avoiding, stored 100 days. The high temperature and high moisture have a great effect on the storage stability of products.
SEM micrographs showed that vitamins A and E nanosphere/microsphere double-layers encapsulation product presented a smooth and compact surface without crack and broken microspheres which indicate the high encapsulation efficiency. The product with beeswax as wall material of nanospheres showed a smoother surface by comparation. Glass transition temperature (Tg) of vitamins A and E nanosphere/microsphere double-layers encapsulation product with glycerin monostearate as wall material of nanospheres by differential scanning calorimetry (DSC) was at 49.265℃with⊿Cp of 0.39J·g-1·℃-1; glass transition temperature of vitamins A and E nanosphere/microsphere double-layers encapsulation product with beeswax as wall material of nanospheres was at 47.51℃w ith⊿C p of 3.04J·g-1·℃-1which indicated the storage stability was good because both of the encapsulation products were at the glass state in normal temperature storage(25℃) .
Thermogravimereic analysis(TGA) showed the thermal stability of the encapsulation product with different nanospheres wall material before and after stored 3 months. The encapsulation product with beeswax as nanospheres wall material showed better thermal stability. The moisture absorption of encapsulation product cause the change of thermogravimetry after 3 months.
The results of X-ray diffraction and DSC analysis towards vitamins A and E nanosphere/microsphere double-layers encapsulation product and wall material indicated that glycerin monostearate intended to be supercooled melt which is in favor of encapsulation during recrystallization. But the vitamins would be expelled during modification of lopid thought storage. Beeswax displayed orthorhombic subcell packing(β’polymorph) which made the encapsulation product good physical stability during storage.
引文
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26.Shefer A. and Shefer S. Novel encapsulation system provides controlled release of food in gredients [J]. Food Technology,2003,57(11):40-42
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33.Shefer; Adi. Multi component controlled release system for oral care, food products, nutracetical, and beverages[P].United States PatentApplication,20030152629.2003-08-14
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26.Shefer A. and Shefer S. Novel encapsulation system provides controlled release of food in gredients [J]. Food Technology,2003,57(11):40-42
27.李东,蒋淑梅,袁秀娟.维生素A分析方法的研究进展[J].食品添加剂,1999,2:28-32
28.鲁志成.从大豆油溜出物中提取维生素E的工艺研究[D]:[硕士学位论文].郑州:郑州工程学院,2004
29.王忠合,朱骏晨,陈惠音.双层原花青素微胶囊的试验研究[J].食品科学,2007,28(1):102-106
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31.Shefer; Adi. Multi component controlled release system for anhydrous cosmetic compositions[P].United States Patent,7115282.2006-10-03
32.Shefer; Adi. Biodegradable bioadhesive controlled release system of nano-particles for oral care products[P].United States Patent,6565873.2003-05-20
33.Shefer; Adi. Multi component controlled release system for oral care, food products, nutracetical, and beverages[P].United States PatentApplication,20030152629.2003-08-14
34.Shefer; Adi. Multicomponent biodegradable bioadhesive controlled release system for oral care products[P]. United States Patent,6589562.2003-07-08
35.Shefer A. and Shefer S. Novel encapsulation system provides controlled release of food ingredients [J]. Food Technology,2003,57(11):40-42
36.常世敏等.浅谈维生素A代谢与生理功能[J].中国食物与营养,2005, 2:55-57.
37.郑景洲.维生素E的功能、吸收与代谢(1)[J].生物学通报,2005,40(11):1-2
38. Sklan D. Donoghue S. Vitamin E response to high dietary vitamin A in chick [J]. J Nutr,1982,112:759-765
39.丁丽敏,张日俊.维生素A最适需要量的研究进展[J].饲料工业,2004,25(10):14-19
40.Luma Baydoum, Pascal Furrer, Robert Gurny. New Surface-active Polymers for ophthalmic formulations: evaluation of ocular toleramce[J]. European Journal of pharmaceutics and Bio-pharmacetics.,2004,58:169-175
41.Gary A. Reineccius. Carbohydrates for Flavor Encapsulation[J]. Food Technology,1991,3:144-149
42.陈晓玲,王璋,许时婴.辛烯基琥珀酸酯化淀粉在微胶囊化桔油中的应用[J].无锡轻工大学学报,2004,3:21-25
43.You-Jin Joen, Thava Vasanthan, Feral Temelli. The suitability of barley and corn starches in their native and chemically modified forms for volatile meat flavor encapsulation[J]. Food Research Internatiol,2003,36:349-355
44.Apinan Soottitantwat, Kohei Takayama, Kenji Okamura. Microencapsulation of l-meathol by spray drying and its release characteristics[J]. Innovative Food Science and Emerging Technologies,2005,6:163-170
45.胡连栋.维甲酸固体脂质纳米粒的研究[D]:[博士论文].沈阳:沈阳药科大学,2005
46.Maria del C. Vasalloa, Maria C. Puppo.Cell wall protein of Kluyveromyces fragilis: Surface and emulsifying properties[J].Lwt, 39(2006):729-739
47.Pearcekn.Kinsella JE.Emulsifying properties of proteins:Evaluation of a turbidinmetric technique [J].J Agric Food Chem,1978,26(3):716-723
48.E.I. Benitez, D.B. Genovese, J.E. Lozano.Scattering efficiency of a cloudy apple juice: Effect of particles characteristics and serum composition[J].Food Research International,2007,40:915-922
49.Hernandez, E., Baker, R. A. Turbidity of beverages with citrus oil clouding agent[J]. Journal of Food Science, 1991,56(4),:1024–1026
50.Hernandez, E., Baker, R. A., & Crandall, P. G. Model for evaluating turbidity in cloudy beverages[J]. Journal of Food Science,1991,56(3):747–750
51.Dickinson, E. Colloidal aspects of beverages[J]. Food Chemistry,1994,51(4):343–347
52.McClement, D. J.. Food emulsion: Principles, particles, and techniques[J].CRC Press,1999:39-81
53.Dobbins, R. A., Jizmagian, G. S. Optical scattering cross sections for polydispersions of dielectric spheres. Journal of the Optical Society of America, 1966, 56(10):1345–1350
54.Lydia C,Vassilios R,Stephen R.Heat stability and emulsifying ability of whole egg and egg yolk as related to heat treatment[J].Food Hydrocolloids,19(2005):533-539
55.Vilma S, Fabien G, Ulrich K. The effect of chitosan on the properties of emulsions stabilized by whey proteins[J].Food Chemistry,102(2007):1048-1054
56.Lennart M. Determination of vitamins A and E in milk powder using supercritical fuild extraction for sample clean-up [J]. Journal of Chromatography A, 2000, 874: 275-283
57.Soledad A. Sonia N. Determination of vitamins A and E in infant formulae by high-performance liquid chromatography [J]. Chromatography A, 1997,778:243-246
58.F.J. Ruperez Direct liquid chromatography method for retinol,α- andγ- tocopherols in rat plasma [J]. Journal of Chromatography B, 2004, 800: 225-230
59.Lubor U. Dagmar S. Optimization and validation of a high performance liquid chromatography method for the simultaneous determination of vitamin A and E in human serum using monolithic column and diode-array detection [J]. Analytica Chimica Acta, 2006, 573-574,267-272
60.安秀林,李庆忠.乳状液稳定性的影响因素和表达[J].张家口农专学报,2003,19(3):29-31
61.Fennema O.R.著.食品化学(第三版)[M].王璋,许时婴,江波等译.北京:中国轻工业出版社, 2003. 312
62.B.Siekmann, K. Westesen. Submicron-sized parenteral carrier systems based on solid lipids[J]. Pharm. Pharmacol Lett, 1992, 1:123-126
63.M.Fuchs,C.Turchiuli. Encapsulation of oil in powder using spray drying and fluidized bed agglomeration [J]. Food Engineering,2006, 75:27-35
64.Lim S.T., Chang E.H. and Chung H.J. Thermal transition characteristics of heat-moisture treated corn and potato starches [J]. Carbohydrate Polymers,2001, 46:107-115
65.苏维彪.维生素A静脉纳米乳剂的制备与研究[D]:[硕士学位论文].吉林:吉林大学生命科学学院,2006
66.国家药典委员会编.中华人民共和国药典2000年版[S].北京:化学工业出版社,2001
67.庄越,曹宝成,萧瑞祥.实用药物制剂技术[M].北京:人民卫生出版社,1999
68.叶盛英,王世岭,高申.重组人表皮生长因子在人工胃液和肠液中的稳定性[J].第二军医大学学报,2003,24(7):810-811
69.何小解,卢向阳,易著文等.模拟人体胃肠道环境对儿茶素稳定性的影响[J].湖南农业大学学报(自然科学版), 2005, 31(5): 527–529
70.沙先谊. 9-硝基喜树碱小肠吸收机理及其自微乳化给药系统的研究[D]: [博士学位论文].上海:复旦大学药学院, 2005
71.宋健,陈磊,李效军.微胶囊化技术及应用[M].北京:化学工业出版社,2001
72.R.H. Müller, Karsten M?der, Sven Gohla. Solid lipid nanospheres (SLN) for controlled drug delivery– a review of the state of the art[J]. Eur J Pharm Biopharm, 2000.50:161-177
73.Suyama, K, Yeow T. and Nakai S. Vitamin A oxidation products responsible for haylike flavor production in nonfat dry milk[J]. Agric. Food Chem,1983,31:22-26
74.V.Jenning.Vitamin A-loaded solid lipid nanospheres for topical use:drug release properties[J].Journal of controlled release, 2000.66:115-126
75.李献文,邱阳.控制释放亲水骨架系统的药物释放动力学研究[J].西北药学杂志,2007,22(2):70-72
76.RitterE.Vitamins in pharmaceutical formulations[J].Pharm. Sci, 1982,71:1073-1096
77.Wood M.C. The influence of light on vitamin A degradation during administration[J]. Clin. Nutr.,1982,1:63-70
78.Wood M.C. and Plane J.H. The degradation of vitamin A exposed to ultraviolet radiation[J]. International Journal of Pharmaceutics,1984,19:207-213
79.杨福愉,林克椿,林其谁等著.生物膜[M].北京:科学出版社, 2005
80.Lim S.T., Chang E.H. and Chung H.J. Thermal transition characteristics of heat-moisture treated corn and potato starches [J]. Carbohydrate Polymers,2001, 46:107-115
81.Saldo J.,Sendra E.,Guanmis B. Changes in water binding in high-pressure treated cheese, measured by TGA (thermogravimetrical analysis)[J]. Innovative Food Science and Emerging Technologies,2002,3:203-207
82.Sindhu Mathew, T. Emilia Abraham. Phisico-chemical characterization of starch ferulates of different degrees of substitution[J]. Food Chemistry,2007,105:579-589
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