降钙素输送系统研究进展.docVIP

 降钙素输送系统研究进展# * 5 10 15 20 25 摘要：降钙素（一个由 32 个氨基酸组成的多肽）是治疗骨质疏松的首选药之一。降钙素对 老年骨质疏松，尤其是绝经后骨质疏松有很好的疗效，但由于其半衰期过短，需频繁注射给 药，病人顺应性很差。目前上市的唯一非注射剂型鼻喷剂生物利用度不到 3%，而且不能保 持长效的血药浓度。大量的研究专注于降钙素输送系统，通过对降钙素的结构修饰、改变输 送载体、加入吸收促进剂等取得了一些效果。本文从鼻腔与肺部给药、口服给药、注射给药 等方向概述了目前降钙素输送系统进展，为以后的研究提供了理论基础。 关键词：鲑鱼降钙素；口服吸收；鼻腔给药；骨质疏松 中图分类号：R94 Research progress on the delivery system of Salmon Calcitonin ZHENG Ruiyuan, CAI Yunpeng, MA Liuqing, YUAN Weien (School of Pharmacy,Shanghai JiaoTong University, Shanghai 200240) Abstract: Salmon Calcitonin (sCT), a small, 32-amino-acid peptide, is very effective for the treatment of osteoporosis, especially for post menopause. SCT is a powerful inhibitor of osteoclast activity that exerts a rapid, transient, and reversible inhibition of bone reabsorption. However, the therapeutic use of exogenously administered sCT is severely hampered by its rapid elimination from the body and short half-life (only about 43 min), which in combination contribute to its poor and variable systemic bioavailability. In addition, sCT injection can cause nausea, abdominal pain, hand swelling and urticaria on the injection sites. The only non-injection formulation, nasal calcitonin spray, whose bioavailability is reportedly 10%–25% compared with the parenteral forms, cannot maintain a long-acting blood concentration. A lot of researches focusing on the structural modification of sCT, adding delivery carrier and absorption-promoting agent have achieved some effects. This article summarized resent studies on the delivery system of sCT. Key words: Salmon Calcitonin; oral adsorption; intranasal route; osteoporosis 30 0 引言 老年人骨质疏松发病率较高，随着社会老龄化的进程，骨质疏松症的发病率呈上升趋势， 预计到 2050 年将增加到 2.21 亿。据估计，全世界每 3 秒就发生一次骨质疏松骨折。二分之 一的女性和五分之一的男性将在 50 岁之后的生活中遭遇一次骨折。对女性而言，这种风险 35 40 比乳腺癌、卵巢癌和子宫癌的风险之和还要大。对于男性，这种风险比前列腺癌的风险更大 [1] 降钙素（一个由 32 个氨基酸组成的多肽）是治疗骨质疏松的首选药之一。降钙素的优 势是其抑制破骨细胞活性，减少破骨细胞数量，抑制骨吸收，降低骨转换，同时降钙素有中 枢神经镇痛作用，能够缓解骨痛。降钙素的劣势是其半衰期过短，需要一天一次注射给药。 另外，降钙素的在相当比例的患者中出现恶心、腹痛、手肿，注射部位出现风疹（一种过敏 -1-  性皮疹）。顾忌副反应