羟丙基-β-环糊精与介质pH值对前列腺素E1溶解度的综合影响

羟丙基-β-环糊精与介质pH值对前列腺素E₁溶解度的综合影响

谷福根^*, 吴春芝, 高永良

1. 内蒙古医学院附属医院药剂部, 内蒙古呼和浩特 010059；
2. 军事医学科学院毒物药物研究所制剂室, 北京 100850

收稿日期:2006-06-15 修回日期:2007-05-10 出版日期:2007-06-15 发布日期:2007-06-15
通讯作者: 谷福根*

Combined effect of hydroxypropyl-β-cyclodextrin and media pH on the solubility of prostaglandin E₁

Fu-Gen Gu^*, Chun-Zhi Wu, Yong-Liang Gao

1.Department of Pharmaceutics, Affiliated Hospital, Inner Mongolia Medial College, Hohhot 010059, China;
2.Department of Pharmaceutics, Institute of Pharmacology and Toxicology, Beijing 100850, China

Received:2006-06-15 Revised:2007-05-10 Online:2007-06-15 Published:2007-06-15
Contact: Fu-Gen Gu*

摘要/Abstract

摘要： 目的研究羟丙基-β-环糊精（HP-β-CD）与介质pH值对前列腺素E1(PGE1)溶解度的综合影响并进一步推导出该药物溶解度的理论方程。方法首先测定药物在不同pH值水中的溶解度；然后分别测定在酸性及中性系列浓度的HP-β-CD溶液中，药物的溶解度；最后推导出以HP-β-CD与介质pH值为变量的药物溶解度方程并对其合理性进行验证。结果溶解度测定结果表明，提高介质的pH值或以HP-β-CD为增溶剂，均可增加PGE1的溶解度。分子型药物或离子型药物与HP-β-CD测得的相溶解度图均为典型的AL型，提示药物结构上的五元碳环部分已嵌入HP-β-CD的疏水性孔穴中，从而形成1: 1摩尔比包合物。结论以HP-β-CD作为增溶剂，同时提高介质的pH值，可对PGE1的溶解度产生协同增加效应。本研究中导出的PGE1溶解度方程，可有效表征HP-β-CD与介质pH值二者对该药物溶解度的综合影响。

关键词: 前列腺素E1, 前列腺素E1, 前列腺素E1, 羟丙基-β-环糊精, 羟丙基-β-环糊精, 羟丙基-β-环糊精, pH, pH, pH, 溶解度, 溶解度, 溶解度, 包合作用, 包合作用, 包合作用, 理论方程, 理论方程, 理论方程

Abstract: Aim To investigate the combined effect of hydroxypropyl-β-cyclodextrin (HP-β-CD) and media pH on the solubility of prostaglandin E1 (PGE1) and construct a theoretical equation for the drug solubility as a function of HP-β-CD concentration and media pH. Methods The solubility of PGE1 under different pH conditions was determined. Then, the drug solubility in different concentrations of HP-β-CD acidic or pH neutral solutions was measured, respectively. Finally, a theoretical solubility equation for the drug as a function of HP-β-CD concentration and media pH was deduced and confirmed in experiment. Results PGE1 was solubilized by HP-β-CD or by increasing media pH. The drug solubility as a function of HP-β-CD concentration was found to follow the AL-type complexation model in acidic or neutral pH media, suggesting that both the ionized and neutral drugs form 1:1 molecular ratio complexes. Conclusions The solubility of PGE1 may be improved by increasing media pH or by using HP-β-CD as a solubilizer. HP-β-CD and media pH can produce combined effect on the solubility of PGE1. The deduced equation for the drug solubility in this study effectively characterizes the roles of HP-β-CD and media pH in determining total solubility of the drug.

Key words: PGE1, PGE1, HP-β-CD, HP-β-CD, pH, pH, Solubility, Solubility, Complexation, Complexation, Theoretical equation, Theoretical equation

中图分类号:

R911.1

Supporting: ^*Corresponding author. Tel.: 86-471-6636646

谷福根^*, 吴春芝, 高永良. 羟丙基-β-环糊精与介质pH值对前列腺素E₁溶解度的综合影响[J]. .

Fu-Gen Gu^*, Chun-Zhi Wu, Yong-Liang Gao. Combined effect of hydroxypropyl-β-cyclodextrin and media pH on the solubility of prostaglandin E₁[J]. .

参考文献

[1] Yamamoto M, Hirayama F, Uekama K. Improvement ofstability and dissolution of prostaglandin E1 by maltosyl-β-cyclodextrin in lyphilized formulation [J]. Chem PharmBull, 1992, 40: 747–751.
[2] Cawello W, Schweer H, Müller R, et al. Metabolism andpharmcokinetics of prostaglandin E1 administered byintravenous infusion in human subjects [J]. Eur J ClinPharmacol, 1994, 46: 275–277.
[3] Cawello W, Leonhardt A, Schweer H, et al. Dose proportionalpharmacokinetics of alprostadil (prostaglandin E1)in healthy volunteers following intravenous infusion [J].Br J Clin Pharmacol, 1995, 40: 273–276.
[4] Wang H. Clinical applications of alprostadil [J]. TianjinPharm, 2002, 14: 20–21.
[5] Yang ZH, Chen YQ, Yang GC. Advance in clinical applicationsof prostaglandin E1 [J]. Chin Pharm, 2001, 10: 52.
[6] Hirayama F, Kurihara M, Uekama K. Mechanisms of decelerationby methylated cyclodextrins in the dehydrationof prostaglandin E2 and the isomerization of prostaglandinA2 in aqueous solution [J]. Chem Pharm Bull, 1986, 34: 5093–5101.
[7] Carpenter TO, Gerloczy A, Pitha J. Safety of parenteralhydroxypropyl-β-cyclodextrin [J]. J Pharm Sci, 1995, 84: 222–225.
[8] Loftsson T, Brewster ME. Pharmaceutical applications ofcyclodextrins, 1. drug solubilization and stabilization [J].J Pharm Sci, 1996, 85: 1017–1025.
[9] Adachi H, Irie T, Hirayama F, et al. Stabilization of prostaglandinE1 in fatty alcohol propylene glycol ointment byacidic cyclodextrin derivative, O-caroxymethyl-O-ethyl-β-cyclodextrin [J]. Chem Pharm Bull, 1992, 40: 1586–1591.
[10] Gu FG, Cui FD, Gao YL. Effect of complexation withhydroxylpropyl-β-cyclodextrin on the solubility, dissolutionrate and chemical stability of prostaglandin E1 [J].Chin Pharm Sci, 2004, 13 (3): 158–165.
[11] Teagarden DL, Anderson BD, Petre WJ. Dehydration kineticsof prostaglandin E1 in a lipid emulsion [J]. PharmRes, 1989, 6: 210–215.
[12] Higuchi T, Connors KA. Phase solubility techniques [J].Adv Anal Chem Instrum, 1965, 4: 117–212.

[1]	李晓辉, 王倩, 刘琛楠, 韩江雪, 刘思含, 刘天俊, 王倩, 关艳, 肖春玲, 王潇, 刘忆霜. 一种新型KPC-2抑制剂: PHT427[J]. 中国药学(英文版), 2023, 32(12): 989-997.
[2]	周锋, 孙丹玲, 王一茹, 张莹, 邓月义. 3',4'-二甲氧基黄酮醇-3-O-β-D-吡喃葡萄糖苷一水合物的多晶型和渗透性[J]. 中国药学(英文版), 2022, 31(8): 634-645.
[3]	Eric Wei Chiang Chan, Siu Kuin Wong, Hung Tuck Chan. Matrine, oxymatrine, and compound Kushen injection from the roots of Sophora flavescens: an overview of their anticancer activities[J]. 中国药学(英文版), 2022, 31(5): 321-333.
[4]	Dewi Melani Hariyadi, Esti Hendradi, Herlina Eka Pratama, Mahardian Rahmadi. Microspheres as pulmonary delivery systems - A review[J]. 中国药学(英文版), 2021, 30(7): 545-555.
[5]	王景茹, 张爽, 李卓越, 徐美琦, 王光雪, 张烜. 用于光动力疗法的pH敏感性碳酸钙-二氢卟吩e6纳米粒的制备与表征[J]. 中国药学(英文版), 2021, 30(11): 904-911.
[6]	余煊, 王欣佩, 雷帆, 王玉刚, 王伟, 丁怡, 邢东明, 袁梽漪, 孙虹, 杜力军. 太子参葛根淫羊藿复合物抗抑郁作用: 与NRSF/NRSE-TPH2 信号相关[J]. 中国药学(英文版), 2021, 30(1): 27-41.
[7]	周楚杭, 胡新平, 刘琦, 王乐淇, 周远航, 靳尧, 刘艳. 增强抗肿瘤药物肿瘤靶向性递送的叶酸修饰的pH敏感聚合物胶束[J]. 中国药学(英文版), 2020, 29(9): 626-636.
[8]	范靖然, 董泽源, 匡易, 周艳霞, 乔雪, 叶敏. 乌拉尔甘草地上部分的化学成分及其PTP1B与α-葡萄糖苷酶抑制活性研究[J]. 中国药学(英文版), 2020, 29(5): 305-313.
[9]	黄晋, 杨玲馨, 杨宁, 袁博文, 张浩, 王梦月. 荨麻抑制前列腺增生药理作用研究[J]. 中国药学(英文版), 2020, 29(4): 236-243.
[10]	Dini Kesuma, Siswandono, Bambang Tri Purwanto, Marcellino Rudyanto. Synthesis and anticancer evaluation of N-benzoyl-N'-phenyltiourea derivatives against human breast cancer cells (T47D)[J]. 中国药学(英文版), 2020, 29(2): 123-129.
[11]	樊文玲, 徐艳, 张心怡, 狄留庆, 李磊. 三元固体分散体提高利多卡因溶解度研究[J]. 中国药学(英文版), 2020, 29(1): 55-65.
[12]	李宁, 梁莹莹, 孙崎, 蒋益民, 李润涛, 叶加. 螺环哌嗪季铵盐化合物LXM-15抗慢性疼痛作用及机制研究[J]. 中国药学(英文版), 2019, 28(6): 371-380.
[13]	李展韬, 廖嫒, 刘曼, 张爽, 冯振汉, 王光雪, 王景茹, 徐美琦, 李卓越, 段晓川, 郝艳丽, 郑秀钗, 李惠, 纳沁, 张华, 刘碧林, 张烜. 聚氨基胺-聚乙二醇-聚氨基胺共聚物的合成及其含阿霉素凝胶的制备与评价[J]. 中国药学(英文版), 2019, 28(5): 316-328.
[14]	王新童, 邹文星, 肖浩然, 谢文军, 李鑫, 卞希玲, 孙崎, 王克威. 呋喃并[3,2-b]吡啶类化合物对α7尼古丁乙酰胆碱受体负向变构调节作用的电生理学评价[J]. 中国药学(英文版), 2019, 28(3): 160-166.
[15]	彭华, 马金魁, 程洁, 黄成志, 张宏斌. Lipocalin噬菌体文库的构建及与FcεRI-α受体结合分子的初步筛选[J]. 中国药学(英文版), 2019, 28(11): 770-777.

羟丙基-β-环糊精与介质pH值对前列腺素E₁溶解度的综合影响

Combined effect of hydroxypropyl-β-cyclodextrin and media pH on the solubility of prostaglandin E₁

PDF (PC)

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 15

编辑推荐

Metrics

本文评价