水溶性烯丙孕素-磺丁基-β-环糊精包合物的制备及表征

doi:10.11843/j.issn.0366-6964.2021.010.023

Abstract

Abstract: To improve the water solubility and bioavailability of altrenogest (ALT), sulfobutyl ether-β-cyclodextrin (SBE-β-CD) was used to encapsulate ALT. In this study, the freeze-drying method was used to prepare the inclusion complex of ALT-SBE-β-CD, to solve the problems of limited clinical use of ALT due to its water insolubility and low bioavailability, so as to broaden the medicinal way of ALT. The inclusion complexes were characterized by Fourier transform infrared spectroscopy, thermogravimetric analysis and microscopy, and the solubility of the inclusion complex was determined by the solubility method. Taking the yield and inclusion rate of inclusion complex as evaluation indexes, the optimal preparation conditions of inclusion complex were selected. The optimal preparation conditions were as follows:at 55℃, the molar ratio of ALT to SBE-β-CD was 1:6, the inclusion time was 5 h, the pH value of the solution was 8, and the amount of solvent was 15 mL (when the dosage of ALT was 0.1 g). The average inclusion rate of ALT was (90.90±1.80)% (n=3), the average drug loading was (4.30±2.30)% (n=3), and the yield of the inclusion complex was (93.19±1.67)%. By Fourier transform infrared spectroscopy, thermogravimetric analysis and microscope imaging method for characterizing the inclusion complex was prepared by, verifiable inclusion complex was successful, solubility method, the test results show that the formation of inclusion complex, its solubility is ALT technical increased 988.86 times, and the inclusion complex has good stability, can meet the requirements of different dosage forms. SBE-β-CD has a good solubilization effect on the drug, which can increase the solubility of the ALT. The preparation method is simple, the conditions are mild, and it is easy for industrial production, which is conducive to the further development and utilization of the drug.

Key words: altrenogest, sulfobutyl ether-β-cyclodextrin, freeze-drying method, inclusion complexes, characterization

CLC Number:

YANG Yushuai, LI Ze, JIN Tianming, YANG Sheng. Preparation and Characterization of a Water-soluble Inclusion Complex of Altrenogest-sulfobutyl Ether-β-cyclodextrin[J]. Acta Veterinaria et Zootechnica Sinica, 2021, 52(10): 2924-2933.

References 31

[1]	BAEK S Y, SA S J, JEONG Y D, et al. Altrenogest affects expression of galectin-3 and fibroblast growth factor 9 in the reproductive tract of sows[J/OL]. Animal Biotechnology, 2020, doi:10. 1080/10495398. 2020. 1726362.
[2]	SHIMATSU Y, UCHIDA M, NIKI R, et al. Effects of a synthetic progestogen, altrenogest, on oestrus synchronisation and fertility in miniature pigs[J]. Vet Rec, 2004, 155(20):633-635.
[3]	ZIECIK A J, KLOS J, PRZYGRODZKA E, et al. Aberrant effects of altrenogest and exposure to exogenous gonadotropins on follicular cysts appearance in gilts[J]. Theriogenology, 2017, 89:250-254.
[4]	ZIECIK A J, DRZEWIECKA K, GROMADZKA-HLIWA K, et al. Altrenogest affects the development and endocrine milieu of ovarian follicles in prepubertal and mature gilts[J]. Biol Reprod, 2020, 103(5):1069-1084.
[5]	LOPES T P, BOLARÍN A, MARTÍNEZ E A, et al. Altrenogest treatment before weaning improves litter size in sows[J]. Reprod Domest Anim, 2017, 52 Suppl 4:75-77.
[6]	才燕, 杨琳燕, 杨升. 烯丙孕素-β-环糊精和羟丙基-β-环糊精包合物制备工艺优选[J]. 动物医学进展, 2020, 41(9):46-50.CAI Y, YANG L Y, YANG S. Optimization of preparation technology of inclusion compound of altrenogest-β-cyclodextrin and its derivatives[J]. Progress in Veterinary Medicine, 2020, 41(9):46-50. (in Chinese)
[7]	ESTIENNE M J, CRAWFORD R J. Characteristics of estrous cycles in gilts treated with gonadotropins after estrus or treatment with a progestogen[J]. Theriogenology, 2015, 83(4):459-465.
[8]	王双, 李艳艳, 杨海峰, 等. 两种烯丙孕素口服液在猪体内的比较药动学研究[J]. 畜牧与兽医, 2018, 50(7):45-50.WANG S, LI Y Y, YANG H F, et al. Comparative pharmacokinetics of two kinds of altrenogest oral liquids in sow[J]. Animal Husbandry & Veterinary Medicine, 2018, 50(7):45-50. (in Chinese)
[9]	方礼禄, 王朝军, 徐利, 等. 四烯雌酮对乏情母猪同期发情的影响[J]. 饲料博览, 2014(10):5-7.FANG L L, WNAG Z J, XU L, et al. Effects of altrenogest on oestrus synchronisation in anestrus pigs[J]. Feed Review, 2014(10):5-7. (in Chinese)
[10]	杨光, 王朝军, 徐利, 等. 四烯雌酮对后备母猪同期发情的影响[J]. 饲料博览, 2014(5):37-39.YANG G, WANG Z J, XU L, et al. Effects of altrenogest treatment on synchronization of gilts estrus[J]. Feed Review, 2014(5):37-39. (in Chinese)
[11]	王忠, 王立琦, 林埴, 等. 同期发情剂四烯雌酮的应用进展[J]. 动物医学进展, 2018, 39(6):95-99.WANG Z, WANG L Q, LIN Z, et al. Progress on estrus synchronization agent altrenogest[J]. Progress in Veterinary Medicine, 2018, 39(6):95-99. (in Chinese)
[12]	李艳艳, 李宇琛, 姚诗贇, 等. 烯丙孕素内服溶液调控母猪同期发情的临床药效试验[J]. 畜牧与兽医, 2019, 51(6):124-127.LI Y Y, LI Y C, YAO S Y, et al. Clinical efficacy of altrenogest oral solution in regulation of synchronous estrus in mature sows[J]. Animal Husbandry & Veterinary Medicine, 2019, 51(6):124-127. (in Chinese)
[13]	杨海峰, 李艳艳, 陈晓兰, 等. 烯丙孕素内服溶液的临床药效和靶动物安全性研究[J]. 中国农业科技导报, 2020, 22(1):78-86.YANG H F, LI Y Y, CHEN X L, et al. Clinical effect and target animal safety of altrenogest oral solution[J]. Journal of Agricultural Science and Technology, 2020, 22(1):78-86(in Chinese)
[14]	王双, 杨海峰, 余波, 等. 烯丙孕素口服液在猪体内的残留消除研究[J]. 畜牧兽医学报, 2018, 49(9):2005-2014.WANG S, YANG H F, YU B, et al. Study on residue elimination of altrenogest oral solution in pigs[J]. Acta Veterinaria Et Zootechnica Sinica, 2018, 49(9):2005-2014. (in Chinese)
[15]	冯言言, 徐恩民, 郑莉, 等. 烯丙孕素口服液调控母猪同期发情的研究进展[J]. 中国兽药杂志, 2018, 52(4):66-72.FENG Y Y, XU E M, ZHENG L, et al. Progress of altrenogest oral solution in the regulation of synchronous estrus of mature sows[J]. Chinese Journal of Veterinary Drug, 2018, 52(4):66-72. (in Chinese)
[16]	夏良友, 李士洋, 李宇琛, 等. 烯丙孕素口服液对靶动物猪的安全性研究[J]. 中国兽药杂志, 2017, 51(10):46-55.XIA L Y, LI S Y, LI Y C, et al. Study on the safety of altrenogest oral solution to sows[J]. Chinese Journal of Veterinary Drug, 2017, 51(10):46-55. (in Chinese)
[17]	李志惠, 蔡兴芳. 烯丙孕素不同饲喂方式对后备母猪同期发情的效果观察[J]. 贵州畜牧兽医, 2019, 43(1):58-60.LI Z H, CAI X F. The effect of different feeding methods of allyl progesterone on estrus in reserve sows during the same period[J]. Guizhou Journal of Animal Husbandry and Veterinary Medicine, 2019, 43(1):58-60. (in Chinese)
[18]	DUA K, PABREJA K, RAMANA M V, et al. Dissolution behavior of β-cyclodextrin molecular inclusion complexes of aceclofenac[J]. J Pharm Bioallied Sci, 2011, 3(3):417-425.
[19]	NANDA A, SAHOO R N, PRAMANIK A, et al. Drug-in-mucoadhesive type film for ocular anti-inflammatory potential of amlodipine:Effect of sulphobutyl-ether-beta-cyclodextrin on permeation and molecular docking characterization[J]. Colloids Surf B Biointerfaces, 2018, 172:555-564.
[20]	FERRATI S, NICOLOV E, BANSAL S, et al. Docetaxel/2-hydroxypropyl β-cyclodextrin inclusion complex increases docetaxel solubility and release from a nanochannel drug delivery system[J]. Curr Drug Targets, 2015, 16(14):1645-1649.
[21]	YAO Y S, XIE Y, HONG C, et al. Development of a myricetin/hydroxypropyl-β-cyclodextrin inclusion complex:Preparation, characterization, and evaluation[J]. Carbohydr Polym, 2014, 110:329-337.
[22]	赵孝先, 高玲, 梁园园, 等. 丁苯酞-磺丁基-β-环糊精包合物的制备与表征[J]. 中国现代应用药学, 2016, 33(6):762-767.ZHAO X X, GAO L, LIANG Y Y, et al. Preparation and characterization of butylphthalide-sulfobutyl-β-cyclodextrin inclusion complex[J]. Chinese Journal of Modern Applied Pharmacy, 2016, 33(6):762-767. (in Chinese)
[23]	蒋娟, 陈萌萌, 王淼, 等. 泊沙康唑-磺丁基-β-环糊精包合物的制备[J]. 沈阳药科大学学报, 2016, 33(7):519-524, 536.JIANG J, CHEN M M, WANG M, et al. Preparation of posaconazole-sulfobutyl ether-β-cyclodextrin inclusion complex[J]. Journal of Shenyang Pharmaceutical University, 2016, 33(7):519-524, 536. (in Chinese)
[24]	宁宁. 难溶性药物增溶材料的研究进展[J]. 新材料产业, 2014(6):46-49.NING N. Research progress of insoluble drug solubilizing materials[J]. Advanced Materials Industry, 2014(6):46-49. (in Chinese)
[25]	陈刚, 何盛江. 银杏内酯n水溶性磺丁基-β-环糊精包合物的研究[J]. 西北药学杂志, 2018, 33(2):230-233.CHEN G, HE S J. Study on the inclusive reaction of sulfobutylether-β-cyclodextrin with ginkgolide N[J]. Northwest Pharmaceutical Journal, 2018, 33(2):230-233. (in Chinese)
[26]	杨云汉, 赵雪秋, 杜瑶, 等. 长春胺与羟丙基-β-环糊精包合物的制备、表征及理论研究[J]. 中草药, 2019, 50(2):352-363.YANG Y H, ZHAO X Q, DU Y, et al. Preparation, spectroscopy and molecular modelling studies of inclusion complex of vincamine with hydroxypropyl-β-cyclodextrin[J]. Chinese Traditional and Herbal Drugs, 2019, 50(2):352-363. (in Chinese)
[27]	王若男, 钱仪敏, 李华, 等. 磺丁基醚-β-环糊精在药物制剂中的应用及安全性研究进展[J]. 中国医药工业杂志, 2019, 50(9):949-957.WANG R N, QIAN Y M, LI H, et al. Application and safety study of sulfobutyl Ether-β-cyclodextrin in pharmaceutical preparations[J]. Chinese Journal of Pharmaceuticals, 2019, 50(9):949-957. (in Chinese)
[28]	周桂芝, 吴珏, 杨雪晗, 等. 水飞蓟素-磺丁基-β-环糊精包合物的制备[J]. 中草药, 2019, 50(17):4100-4107.ZHOU G Z, WU J, YANG X H, et al. Preparation of silymarin sulfobutyl-β-cyclodextrin inclusion complex[J]. Chinese Traditional and Herbal Drugs, 2019, 50(17):4100-4107. (in Chinese)
[29]	吴倩, 李鑫宇, 王薪默, 等. 基于磺丁基-β-环糊精包合技术的姜黄素舌下片的制备及质量评价[J]. 现代中药研究与实践, 2019, 33(2):49-53.WU Q, LI X Y, WANG X M, et al. Preparation and quality evaluation of curcumin sublingual tablet based on sulfobutyl-β-cyclodextrin inclusion technology[J]. Research and Practice on Chinese Medicines, 2019, 33(2):49-53. (in Chinese)
[30]	娄兴维, 罗志军, 胡鹏刚, 等. 四种β-环糊精制备鞣花酸包合物的抗氧化性研究[J]. 中国酿造, 2020, 39(4):114-120.LOU X W, LUO Z J, HU P G, et al. Antioxidant property of ellagic acid inclusion complex prepared by four β-cyclodextrins[J]. China Brewing, 2020, 39(4):114-120. (in Chinese)
[31]	吴传红, 仲瑞雪, 魏庭森, 等. 薄荷油-磺丁基醚-β-环糊精的包合物的制备及表征[J]. 中国食品添加剂, 2020, 31(9):14-18.WU C H, ZHONG R X, WEI T S, et al. Preparation and characterizations of pennyroyal-SBE-β-CD inclusion complexes[J]. China Food Additives, 2020, 31(9):14-18. (in Chinese)

Preparation and Characterization of a Water-soluble Inclusion Complex of Altrenogest-sulfobutyl Ether-β-cyclodextrin

PDF (PC)

Knowledge

Abstract

Cite this article

share this article

References 31

Related Articles 15

Recommended Articles

Metrics

Comments

[1]	FEI Guoqing, NING Zhiyuan, ZHAO Zefang, LIU Yanqiu, LIU Tengfei, LI Xian, CONG Rihua, CHEN Hong, CHEN Shulin. Isolation, Identification of Luteal Cells from Cows during Pregnancy and Investigation of Their Culture Characteristics [J]. Acta Veterinaria et Zootechnica Sinica, 2024, 55(5): 2214-2225.
[2]	ZHANG Jiaqi, JIA GA Gexi, ZHOU Qun, SONG Xin, ZHANG Bin. Metagenomics Analysis of Virus Populations in Piglet Diarrheal Feces from Intensive Pig Farms in Sichuan Province [J]. Acta Veterinaria et Zootechnica Sinica, 2023, 54(6): 2478-2486.
[3]	ZHANG Ting, FENG Tao, YANG Jinke, HAO Yu, YANG Xing, ZHANG Dajun, SHI Xijuan, YAN Wenqian, CHEN Lingling, LIU Xiangtao, ZHENG Haixue, ZHANG Keshan. Construction and Growth Characteristics of Recombinant African Swine Fever Virus with Conditional Deletion of D1133L Gene [J]. Acta Veterinaria et Zootechnica Sinica, 2023, 54(2): 706-714.
[4]	CAI Weimin, LI Wenjing, WANG Lele, SU-DING Zeyang, ZHU Yu, LIU Dandan, XU Jinjun, TAO Jianping. Preparation and Characterization of Monoclonal Antibodies against the Gametocyte Antigen EnGAM22 of Eimeria necatrix [J]. Acta Veterinaria et Zootechnica Sinica, 2022, 53(3): 875-882.
[5]	LI Shuya, HUANG Zan, ZHU Weiyun, LIN Yan. Biological Characteristics and Genomic Analysis of a Lytic Proteus mirabilis Phage with C3 Morphotype [J]. Acta Veterinaria et Zootechnica Sinica, 2021, 52(4): 1069-1078.
[6]	MENG Zhen, SUN Mengke, XU Yongde, QIN Tao, REN Zhe. Structural Characterization and Immune Enhancement of Phyllanthus emblica Polysaccharide [J]. Acta Veterinaria et Zootechnica Sinica, 2021, 52(12): 3627-3640.
[7]	YU Ruihong, MENG Zhen, SUN Mengke, CHEN Shixiong, ZHANG Junwen, HUANG Yifan, QIN Tao, REN Zhe. Structural Characterization and Immunomodulatory Activities of Polysaccharide Extracted from Lagotis brevituba Maxim [J]. Acta Veterinaria et Zootechnica Sinica, 2021, 52(11): 3270-3281.
[8]	ZHAO Yuzhong, DING Guofei, LIU Jiaqi, LI Li, LI Yingchao, WANG Bin, SHAO Qingyuan, FENG Jian, GUO Lihong, LIU Sidang, XIAO Yihong. Molecular Characterization of a H9N2 Subtype Swine Influenza Virus [J]. Acta Veterinaria et Zootechnica Sinica, 2020, 51(9): 2312-2318.
[9]	JIANG Xingcan, LI Bing, YANG Min, ZHANG Jiyu. Characterization and Analysis of SAR/β-CD Inclusion Complex Microcapsules [J]. Acta Veterinaria et Zootechnica Sinica, 2020, 51(8): 1993-2002.
[10]	ZHANG Yuyu, ZHANG Min, HUANG Zan, LIN Yan. Isolation and Characterization of a Lytic Polyvalent Bacteriophage Infecting Salmonella choleraesuis and Escherichia coli [J]. Acta Veterinaria et Zootechnica Sinica, 2020, 51(8): 2032-2038.
[11]	HAN Yuying, XIE Libao, LI Yongfeng, QIU Huaji. Generation and Characterization in Rabbits of a Reporter Classical Swine Fever Virus Vaccine C-strain Expressing the Enhanced Green Fluorescent Protein [J]. Acta Veterinaria et Zootechnica Sinica, 2020, 51(7): 1699-1709.
[12]	LI Ran, TANG Cheng, LUO Xue, YUE Hua. Isolation and Gene Sequence Analysis of G6P[11] Bovine Rotavirus HY-1 Strain from Yak [J]. ACTA VETERINARIA ET ZOOTECHNICA SINICA, 2019, 50(3): 592-601.
[13]	HE Qifu, TANG Cheng, GUO Zijing, TAN Shuo, ZHANG Bin, YUE Hua. Amplification, Sequence Analysis of Bovine Coronavirus Genes and Isolation of the Viruses from Yak [J]. ACTA VETERINARIA ET ZOOTECHNICA SINICA, 2019, 50(2): 343-353.
[14]	WANG Shuang, YANG Hai-feng, YU Bo, LI Shi-yang, ZHENG Yu-ji, BU Shi-jin. Study on Residue Elimination of Altrenogest Oral Solution in Pigs [J]. ACTA VETERINARIA ET ZOOTECHNICA SINICA, 2018, 49(9): 2005-2014.
[15]	GAO Xiao-long, WEI Hai-tao, SONG Yan-jun, WANG Yue, YIN Yu-qing, WANG Lin, MEI Li, FENG Xiao-yu. Progress Research of Influenza D Virus [J]. ACTA VETERINARIA ET ZOOTECHNICA SINICA, 2018, 49(7): 1327-1333.