肠溶型饲料添加剂甘氨酸亚铁的制备与表征
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摘要
以聚丙烯酸树脂为肠溶衣材料,以滑石粉为抗黏剂,采用底喷法制备了肠溶型甘氨酸亚铁微丸.利用响应曲面法和正交实验探究肠溶包衣液的最佳处方和工艺参数.采用傅里叶变换红外光谱(FTIR)、聚焦离子束-扫描电子显微镜(FIB-SEM)及智能溶出仪进行表征.结果表明:当包衣液中聚丙烯酸树脂的质量浓度为0.059 2 g/mL、抗黏剂质量浓度为0.031 3 g/mL时,在模拟肠液环境下微丸的释放率达到95.5%.在风机转动频率为17 Hz、供液转速为8 r/min、物料温度为43℃、包衣操作时长为0.5 h条件下,微丸颗粒的完整率达到96.7%.由FTIR分析可知,微丸的药效结构完整.由SEM、FIB-SEM观察可知,在制备的肠溶衣微丸中,载药衣、隔离衣、肠溶衣的厚度分别为187.8、38.8、668.6 nm,且结构规整均匀.
The enteric-soluble glycine ferrous pellets were prepared by using a polyacrylic resin as an enteric coating material and talc powder as an anti-adhesive by means of bottom spray. The response surface methodology and orthogonal experiments were used to explore the optimal formulation and process parameters of enteric coating liquid,and the glycine ferrous pellets were characterized by Fourier Transform Infrared Spectroscopy( FTIR),Focused Ion Beam-Scanning Electron Microscope( FIB-SEM) and intelligent dissolution apparatus.The results showed that the concentration of the coating liquid was 0. 059 2 g/mL,and the concentration of the anti-adhesive agent was 0.031 3 g/mL,which reached 95.5% release in the simulated intestinal juice environment. When the fan frequency is 17 Hz,the liquid supply speed was 8 r/min,and the material temperature was 43 ℃,the coating operation reaches a complete rate of 96.7% at 0.5 h. FTIR analysis showed that the pharmacophore structure of the pellets was complete. SEN and FIB-SEM observation showed that the prepared enteric coated pellets had a uniform structure with a shell thickness of 187.8 nm,an isolation thickness of 38.8 nm,and an enteric coating thickness of 668.6 nm.
The enteric-soluble glycine ferrous pellets were prepared by using a polyacrylic resin as an enteric coating material and talc powder as an anti-adhesive by means of bottom spray. The response surface methodology and orthogonal experiments were used to explore the optimal formulation and process parameters of enteric coating liquid,and the glycine ferrous pellets were characterized by Fourier Transform Infrared Spectroscopy( FTIR),Focused Ion Beam-Scanning Electron Microscope( FIB-SEM) and intelligent dissolution apparatus.The results showed that the concentration of the coating liquid was 0. 059 2 g/mL,and the concentration of the anti-adhesive agent was 0.031 3 g/mL,which reached 95.5% release in the simulated intestinal juice environment. When the fan frequency is 17 Hz,the liquid supply speed was 8 r/min,and the material temperature was 43 ℃,the coating operation reaches a complete rate of 96.7% at 0.5 h. FTIR analysis showed that the pharmacophore structure of the pellets was complete. SEN and FIB-SEM observation showed that the prepared enteric coated pellets had a uniform structure with a shell thickness of 187.8 nm,an isolation thickness of 38.8 nm,and an enteric coating thickness of 668.6 nm.
引文
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[18]李海杰.肠溶缓释薄膜性能的研究及其应用[D].杭州:浙江大学,2014.LI H J.Study on properties and applications of entericcoated sustained-release films[D].Hangzhou:Zhejiang University,2014.
[19]THOMSON A B,SHAVER C,LEE D J,et al.Effect of varying iron stores on site of intestinal absorption of cobalt and iron[J].American Journal of Physiology-Legacy Content,1971,220(3):674-678.
[20]杨军星,王琦,王媛媛,等.双重载药多层海藻酸盐-壳聚糖缓释微球的制备及体外释放[J].高等学校化学学报,2015,36(5):1025-1032.YANG J X,WANG Q,WANG Y Y,et al.Preparation and in vitro release of multilayer alginate chitosan microspheres loading VEGF and Vancomycin[J].Chemical Journal of Chinese Universities,2015,36(5):1025-1032.
[21]林烨,吕英军,张晓辉,等.替米考星肠溶颗粒对猪的安全性试验[J].中国兽药杂志,2016,50(10):22-31.LIN Y,LU Y J,ZHANG X H,et al.The safety test of enteric-coated Tilmicosin pellets in swine[J].Chinese Journal of Veterinary Drug,2016,50(10):22-31.
[22]姜辉,翟林峰.包衣甘氨酸亚铁微丸的制备及其性能研究[J].安徽化工,2018(4):18-21.JIANG H,ZHAI L F.Preparation and properties of coated ferrous glycinate pellets[J].Anhui Chemical Industry,2018(4):18-21.
[23]储呈慧.《食品安全国家标准-食品添加剂使用标准》解读[J].食品安全导刊,2015(24):28.
[24]国家药典委员会.中华人民共和国兽药典[M].北京:化学工业出版社,2015.
[25]尤孝庆,卢丹,许美蓉.缓释微丸工艺研究[J].中国医药工业杂志,1996(4):163-165.YOU X Q,LU D,XU M R.Study on sustained release pellets[J].Chinese Journal of Pharmaceuticals,1996(4):163-165.
[26]ANDRE M,RAMOS P,MATOS J.Absorption of Cu-64,Zn-65,Mo-99,and Fe-59 from ligated segments of the rat gastrointestinal tract[J].Journal of Nutrition,1965,86:120-124.
[27]杨文正.动物矿物质营养[M].北京:中国农业出版社,1996.
[28]鲁晓芳,俞火明.硫酸蛋氨酸合锌工艺研究[J].精细化工中间体,1997(1):28-31.LU X F,YU H M.A technical study on zinc methionine sulphate complex[J].Hunan Chemical Industry,1997(1):28-31.
[29]唐星.口服缓控释制剂[M].北京:人民卫生出版社,2007.
[2]SVOBODA M,DRABEK J,KREJCI J,et al.Impairment of the peripheral Lymphoid compartment in iron-deficient piglets[J].Journal of Veterinary Medicine Series B,2004,51(5):231-237.
[3]ETTLE T,SCHLEGEL P,ROTH F X.Investigations on iron bioavailability of different sources and supply levels in piglets[J].Journal of Animal Physiology and Animal Nutrition,2008,92(1):35-43.
[4]孙效名,吴信,印遇龙,等.幼龄动物铁吸收及其调控[J].动物营养学报,2012,24(6):1001-1006.SUN X M,WU X,YIN Y L,et al.Iron absorption and its regulation in the Neonate[J].Chinese Journal of Animal Nutrition,2012,24(6):1001-1006.
[5]VEGARUE G E,LANGSRUD T,SVENNING C.Mineralbinding milk proteins and peptides;occurrence,biochemical and technological characteristics[J].British Journal of Nutrition,2000,84:91-98.
[6]PETERS J C,MAHAN D C.Effects of neonatal iron status,iron injections at birth,and weaning in young pigs from sows fed either organic or inorganic trace minerals[J].Journal of Animal Science,2008,86(9):2261-2269.
[7]HERTR AMPF E,OLIVARRES M.Iron amino acid chelates[J].International Journal for Vitamin and Nutrition Research,2004,74(6):35-43.
[8]ASHMEAD H D.The absorption and metabolism of iron amino acid chelate[J].Archivos Latinoamericanos De Nutricion,2001,51:13-21.
[9]SINGH A K,GHOSH T K,HALDAR S.Effects of methionine chelate-or yeast proteinate-based supplement of copper,iron,manganese and zinc on Broiler growth performance,their distribution in the Tibia and excretion into the environment[J].Biological Trace Element Research,2015,164(2):253-260.
[10]马文强.甘氨酸亚铁螯合物的肠道吸收特点及其生物学效应研究[D].杭州:浙江大学,2010.MA W Q.Intestinal absorption characteristics of ferrous glycinate chelate and its biological effects[D].Hangzhou:Zhejiang University,2010.
[11]钱方,蒋雪涛,王安文.微丸的进展[J].中国医药工业杂志,1996(1):41-46.QIAN F,JIANG X T.Recent advances in pellets[J].Chinese Journal of Pharmaceuticals,1996(1):41-46.
[12]刘元江,李高,沈灵佳,等.微丸辅料研究进展[J].医药导报,2008,27(5):564-567.
[13]黄涓涓,谢俊,黄春玉,等.膜控型微丸的研究与应用进展[J].药学与临床研究,2011,19(1):42-46.HUANG J J,XIE J,HUANG C Y,et al.Development of film-controlled Pellets in research and application[J].Pharmaceutical and Clinical Research,2011,19(1):42-46.
[14]谢博媛,李国明,刘聪,等.拉米夫定-海藻酸钠/壳聚糖核壳结构微球的制备及释药性能[J].华南师范大学学报(自然科学版),2015,47(4):46-51.XIE B Y,LI G M,LIU C,et al.Preparation of Lamivudinesodium alginate/chitosan core-shell microspheres and the drug-release performance[J].Journal of South China Normal University(Natural Science Edition),2015,47(4):46-51.
[15]冯淑莹,李国明,侯琼,等.金雀异黄素/壳聚糖微球的制备及其释药性能[J].华南师范大学学报(自然科学版),2013,45(5):64-67.FENG S Y,LI G M,HOU Q,et al.Preparation of genisteinchitosan microspheres and their drug-releasing performances[J].Journal of South China Normal University(Natural Science Edition),2013,45(5):64-67.
[16]程利霞,李国明,钱程根,等.那格列奈壳聚糖微球的制备及其释放性能[J].华南师范大学学报(自然科学版),2013,45(3):68-72.CHENG L X,LI G M,ZHANG C G,et al.Study on preparations and properties of nateglinide-chitosan drugloading microspheres[J].Journal of South China Normal University(Natural Science Edition),2013,45(3):68-72.
[17]刘聪,李国明,林跃,等.盐酸阿米替林/壳聚糖微球的制备[J].华南师范大学学报(自然科学版),2008(4):81-86.LIU C,LI G M,LIN Y,et al.Preparation of amitriptyline hydrochloride-chitosan microspheres[J].Journal of South China Normal University(Natural Science Edition),2008(4):81-86.
[18]李海杰.肠溶缓释薄膜性能的研究及其应用[D].杭州:浙江大学,2014.LI H J.Study on properties and applications of entericcoated sustained-release films[D].Hangzhou:Zhejiang University,2014.
[19]THOMSON A B,SHAVER C,LEE D J,et al.Effect of varying iron stores on site of intestinal absorption of cobalt and iron[J].American Journal of Physiology-Legacy Content,1971,220(3):674-678.
[20]杨军星,王琦,王媛媛,等.双重载药多层海藻酸盐-壳聚糖缓释微球的制备及体外释放[J].高等学校化学学报,2015,36(5):1025-1032.YANG J X,WANG Q,WANG Y Y,et al.Preparation and in vitro release of multilayer alginate chitosan microspheres loading VEGF and Vancomycin[J].Chemical Journal of Chinese Universities,2015,36(5):1025-1032.
[21]林烨,吕英军,张晓辉,等.替米考星肠溶颗粒对猪的安全性试验[J].中国兽药杂志,2016,50(10):22-31.LIN Y,LU Y J,ZHANG X H,et al.The safety test of enteric-coated Tilmicosin pellets in swine[J].Chinese Journal of Veterinary Drug,2016,50(10):22-31.
[22]姜辉,翟林峰.包衣甘氨酸亚铁微丸的制备及其性能研究[J].安徽化工,2018(4):18-21.JIANG H,ZHAI L F.Preparation and properties of coated ferrous glycinate pellets[J].Anhui Chemical Industry,2018(4):18-21.
[23]储呈慧.《食品安全国家标准-食品添加剂使用标准》解读[J].食品安全导刊,2015(24):28.
[24]国家药典委员会.中华人民共和国兽药典[M].北京:化学工业出版社,2015.
[25]尤孝庆,卢丹,许美蓉.缓释微丸工艺研究[J].中国医药工业杂志,1996(4):163-165.YOU X Q,LU D,XU M R.Study on sustained release pellets[J].Chinese Journal of Pharmaceuticals,1996(4):163-165.
[26]ANDRE M,RAMOS P,MATOS J.Absorption of Cu-64,Zn-65,Mo-99,and Fe-59 from ligated segments of the rat gastrointestinal tract[J].Journal of Nutrition,1965,86:120-124.
[27]杨文正.动物矿物质营养[M].北京:中国农业出版社,1996.
[28]鲁晓芳,俞火明.硫酸蛋氨酸合锌工艺研究[J].精细化工中间体,1997(1):28-31.LU X F,YU H M.A technical study on zinc methionine sulphate complex[J].Hunan Chemical Industry,1997(1):28-31.
[29]唐星.口服缓控释制剂[M].北京:人民卫生出版社,2007.