Otsuka Makoto, Oshinbe Ayako, Legeros Racquel Z, Tokudome Yoshihiro, Ito Atsuo, Otsuka Kuniko, Higuchi William I
Faculty of Pharmacy, Research Institute of Pharmaceutical Sciences, Musashino University, Shinmachi 1-1-20, Nishi-Tokyo 202-8585, Japan.
J Pharm Sci. 2008 Jan;97(1):421-32. doi: 10.1002/jps.21131.
The purpose of this study was to evaluate the therapeutic efficacy of a new calcium phosphate (CaP)-based formulation in improving the bone mineral deficiency in ovariectomized (OVX) rats. The ions release experiments for CaP preparations (G2: 0.46% Mg, 5.78% Zn, and 2.5% F; G3:3.1% Mg, 0.03% Zn, and 3.01% F; G4: 1.25% Mg, 1.77% Zn, 1.35% F) and of a Zn-TCP (G1: 6.17% Zn) powders, the initial Mg and Zn ion release rates of MZF-CaPs were performed in acetate buffer at pH 4.5 (37 degrees C). Wistar rats were divided into six groups including a normal (not OVX) group (GN) and a control, OVX group (GC). Rats in groups GC, G1, G2, G3, G4 were OVX. Suspensions consisting of CaP preparations (G2, G3, G4) and of a Zn-TCP (G1) powders were injected in the right thighs of OVX rats in all groups except for GN and GC, once a week for 4 weeks. GN and GC rats were injected with saline solutions. Plasma was analyzed for Zn land alkaline phosphatase levels. The bone mineral density (BMD) was measured using DEXA and the bone (femur) strength determined using three-point-bending analysis. G1 and G2 groups showed high plasma Zn levels. The area under the curve of plasma Zn was significantly greater in the G1, G2, and GN groups than in the G3, G4, and GC groups (p < 0.05). The BMD and bone mechanical strength of the right femur were significantly higher in the G1, G2, G3, and G4 groups than GC group on day 28. The right femur had significantly greater BMD and bone mechanical strength than the left femur in G1, G2, G3, and G4 groups. However, there was no significant difference in the BMD of the right femur between the G1, G2, G3, and G4 groups. Results indicate that the new injectable CaP formulations are effective in improving bone properties of OVX rats and may be useful in osteoporosis therapy.
本研究的目的是评估一种新型磷酸钙（CaP）基制剂在改善去卵巢（OVX）大鼠骨矿物质缺乏方面的治疗效果。对CaP制剂（G2：0.46%镁、5.78%锌和2.5%氟；G3：3.1%镁、0.03%锌和3.01%氟；G4：1.25%镁、1.77%锌、1.35%氟）和一种锌-磷酸三钙（Zn-TCP，G1：6.17%锌）粉末进行离子释放实验，在pH 4.5（37℃）的醋酸盐缓冲液中测定MZF-CaPs的初始镁和锌离子释放速率。将Wistar大鼠分为六组，包括正常（未去卵巢）组（GN）和对照组、去卵巢组（GC）。GC、G1、G2、G3、G4组的大鼠进行了去卵巢手术。除GN和GC组外，给所有组去卵巢大鼠的右大腿注射由CaP制剂（G2、G3、G4）和Zn-TCP（G1）粉末组成的悬浮液，每周一次，共4周。给GN和GC组大鼠注射盐溶液。分析血浆中的锌和碱性磷酸酶水平。使用双能X线吸收法（DEXA）测量骨矿物质密度（BMD），并使用三点弯曲分析测定骨（股骨）强度。G1和G2组的血浆锌水平较高。G1、G2和GN组血浆锌曲线下面积显著大于G3、G4和GC组（p<0.05）。在第28天，G1、G2、G3和G4组右股骨的BMD和骨力学强度显著高于GC组。在G1、G2、G3和G4组中，右股骨的BMD和骨力学强度显著高于左股骨。然而，G1、G2、G3和G4组右股骨的BMD之间没有显著差异。结果表明，新型可注射CaP制剂在改善去卵巢大鼠的骨特性方面有效，可能对骨质疏松症治疗有用。
