目的 研究一种在研的新型抗骨质疏松二膦酸盐类药物(SC)对骨的靶向性和其在体内的动态变化过程。方法 采用放射性示踪技术观察SC在兔体内的分布情况和对骨的靶向性，通过放射性核素99Tcm标记SC，将标记后的99Tcm-SC注射进兔体内，进行SPECT骨显像，采集12 h内的显像图进行分析。结果 SC的99Tcm标记率在12 h内能保持在90%以上，证明99Tcm-SC的体外稳定性良好。12 h内的兔骨显像图提示SC对骨的靶向性与骨显像剂MDP相当，这为进一步开展SC的非临床和临床研究提供了数据支持和依据。结论 SC具有开发成为全新一代抗骨质疏松新药的潜力。
Abstract
OBJECTIVE To study the bone-targeting potential and dynamic changing process in vivo of a new type of anti-osteoporosis bisphosphonate drug under research(SC). METHODS The distribution in rabbits and bone-targeting of SC was observed by isotope tracer technique. 99Tcm-SC was injected into the rabbits, then the SPECT images were collected and analyzed in 12 h. RESULTS The labeling rate of 99Tcm-SC could be maintained above 90% within 12 h, which proved the good stability of 99Tcm-SC in vitro. The rabbit bone imaging showed that the targeting of SC to bone was equivalent to MDP, a bone imaging agent. CONCLUSION This study provides valuable data for the non-clinical and clinical studies of SC. SC has a good potential for being developed into a new generation of anti-osteoporosis drug.
关键词
含硒二膦酸盐 /
二膦酸盐 /
骨质疏松 /
99Tcm /
骨显像 /
骨靶向性
{{custom_keyword}} /
Key words
selenium-containing bisphosphonate /
bisphosphonate /
osteoporosis;99Tcm /
Bone Imaging /
Bone-targeting
{{custom_keyword}} /
中图分类号：
R965
{{custom_clc.code}}
({{custom_clc.text}})
{{custom_sec.title}}
{{custom_sec.title}}
{{custom_sec.content}}
参考文献
[1] LIU Z Y,LI Z R. Advances in osteoporosis therapy. Chin Pharm J(中国药学杂志),2006,41(10):721-725.
[2] HE J H,TONG N W,LI H Q,et al. Effects of L-threonate on bone resorption by osteoclasts in vitro. J Sichuan Univ(四川大学学报),2005,36(2):225-228.
[3] LI S X,WANG Z Q,HU W X,et al. Research progress of bisphosphonate for treatment and prevention of postmenopausal osteoporosis. Chin Pharm J(中国药学杂志),1997,32(2):65-68.
[4] ODVINA C V,ZERWEKH J E,RAO D S,et al. Severely suppressed bone turnover:a potential complication of alendronate therapy. J Clin Endocrinol Metab,2005,90(3):1294-1301.
[5] HUANG J Q,FU D X, SUN C H. ADRs Induced by diphosphonate and notice in the application of diphosphonate. Eval Anal Drug Use Hosp China(中国医院用药评价与分析),2008,8(5):325-327.
[6] MAGGIO D,BARABANI M,PIERANDREI M,et al. Marked decrease in plasma antioxidants in aged osteoporotic women:results of a cross-sectional study. J Clin Endocrinol Metab,2003,88(4):1523-1527.
[7] ALTINDAG O,EREL O,SORAN N,et al. Total oxidative/anti-oxidative status and relation to bone mineral density in osteoporosis. Rheumatol Int,2008,28(4):317-321.
[8] LI M Q,WANG H,DENG Q M, et al. A bisphosphonate compound and preparation methods:China,CN102453050A. 2012-05-16.
[9] QIAN M L,MA Y,WANG P M,et al. Research progress of bisphosphonates as bone targeted carrier for treatment of common bone disease. J Emerg Tradit Chin Med(中国中医急症),2010,19(3):498-499.
PIERCE W M, LEONARD W C. Bone-targeted inhibitors of carbonic anhydrase:USA,EP201057. 1986-11-12.
GU J J,DENG Y J.progress on bone-targeting drugs and related carriers. Chin J Pharm(中国药剂学杂志),2009,7(3):191-197.
ZHAI H Z,LUO S N,WANG Y,et al. Synthesis of M4IDP and Optimum Labeling Conditions of 99Tcm-M4IDP. J Isotop(同位素),2010,23(4):225-229.
WIDLER L,JAEGGI K A,GLATT M,et al. Highly potent geminal bisphosphonates. From pamidronate disodium (Aredia) to zoledronic acid (Zometa). J Med Chem,2002,45(17):3721-3738.
MORENO-REYES R, EGRISE D, NEVE J,et al. Selenium deficiency-induced growth retardation is associated with an impaired bone metabolism and osteopenia. J Bone Miner Res, 2001, 16(8):1556-1563.
TURAN B,CAN B,DELILBASI E. Selenium combined with vitamin E and vitamin C restores structural alterations of bones in heparin-induced osteoporosis. J Clin Rheumatol,2003,22(6):432-436.
FANG Y,PENG Q W. Progress on the methods of targeted evaluation of pharmaceutical preparations. China Pharm(中国药师),2013,16(8):1232-1234.
{{custom_fnGroup.title_cn}}
脚注
{{custom_fn.content}}
PDF(920 KB)
