骨肿瘤治疗药物~（186）Re－HEDP的制备及动物实验

１８３Ｒｅ－ＨＥＤＰ注射液的标记年＞９５％，该制剂为无色、澄明液体，ｐＨ～５．动物体内分布实验表明：静脉注射药物后３／小时，小鼠骨摄取量最高，为２８８±３５（％剂量／ｇ组织×１００，下同），９６小时以后仍有１３５±２４；而肌肉中的含量较低，为０．４±０．１．大白兔骨显像图像清晰；能清晰显示病人的骨肿瘤；给小鼠注射相当于正常成人用量８００倍的１８６Ｒｅ－ＨＥＤＰ，未发现各重要器官有组织学的异常。     

^90Y—EDTMP治疗骨转移癌的实验及临床报告

利用趋骨核素及其标记化合物有选择性地被骨骼摄取,并在病灶内异常浓聚的原理,用~(90)Y-EDTMP治疗23例重症多发性骨转移癌患者。成人每次用量7.4MB_q～9.25MB_q/kg,总量不超过650MB_q,间隔一个月重复用药一次为一个疗程,有效率87.0％,显效率47.8％.平均缓解期64.8d。动物实验结果表明,注射一定量(74MB_q/Kg)的~(90)Y-EDTMP1周～2周出现骨髓抑制现象,外周血象亦发生相应变化,4周～5周后逐渐恢复正常。     

帕米膦酸二钠联合化疗治疗恶性肿瘤骨转移疗效观察

[目的]观察帕米膦酸二钠联合化疗治疗恶性肿瘤骨转移的疗效。[方法]52例恶性肿瘤患者随机分为两组,每组26例。治疗组接受帕米膦酸二钠联合化疗,对照组单用化疗,两组化疗方案相同。[结果]疼痛总有效率治疗组为80.8%,对照组为46.2%,治疗组疗效优于对照组(P<0.05)。两组均无明显的不良反应。[结论]帕米膦酸二钠联合化疗治疗恶性肿瘤骨转移有较好疗效。     

双膦酸类药物研究进展

综述双膦酸类药物的化学（合成、含水不同的晶型、分类和构效关系）、药理（药效特点、作用机制、药物动力学和毒理）及其治疗骨吸收性疾病（包括变形性骨炎、高钙血症、溶骨性骨转移和骨质疏松症）的进展     

188 Re-羟乙基二膦酸与帕米膦酸二钠联合治疗乳腺癌骨转移的临床价值

目的探讨188Re-羟乙基二膦酸(188Re-HEDP)联合帕米膦酸二钠治疗乳腺癌骨转移的临床价值.方法48例乳腺癌多发骨转移患者随机分为3组,分别接受188Re-HEDP、帕米膦酸二钠的单独治疗及两者的联合治疗.结果188Re-HEDP组、帕米膦酸二钠组、联合治疗组止痛有效率分别为73.3%、80.0%和100.0%;骨转移病灶控制有效率分别为40.0%、33.3%和66.7%.联合治疗组疗效明显高于188Re-HEDP组和帕米膦酸二钠组(P均＜0.05),而188Re-HEDP组与帕米膦酸二钠组间差异无统计学意义(P＞0.05).结论188Re-HEDP联合帕米膦酸二钠治疗乳腺癌骨转移,在止痛、骨转移病灶控制方面疗效明显,优于各药单药治疗.     

Pharmacological profiles of an anticholinergic agent, phencynonate hydrochloride, and its optical isomers

AIM: To comparatively study the pharmacological profiles of 3-methyl-3-azabicyclo(3,3,1)nonanyl-9-alpha-yl-alpha-cyclopentyl-alpha-phenyl-alpha-glycolate (phencynonate hydrochloride, CPG), an anticholinergic agent, and its enantiomers [R(-)-and S(+)-CPG]. METHODS: The affinity and relative efficacy were tested using radioligand-binding assay with muscarinic acetylcholine receptors from rat cerebral cortex. The pharmacological activities were assessed in three individual experiments: (1) potentiating the effect of subthreshold hypnotic dose of sodium pentobarbital; (2) inhibiting oxotremorine-induced salivation; and (3) inhibiting the contractile response to carbachol. RESULTS: The order of potency of phencynonate hydrochloride and its optical isomers to inhibit the binding of [3H]quinuclidinyl benzilate ([3H]QNB) was R(-)-CPG (K(i)=46.49+/-1.27 nmol/L)>CPG(K(i)=271.37+/-72.30nmol/L)>S(+)-CPG(K(i)=1263.12+/-131.64 nmol/L). The results showed that R(-)-CPG had the highest affinity to central muscarinic receptors among the three compounds, but did not show any central depressant effects at dose from 10.00 to 29.15 mg/kg. CPG increased the effects of subthreshold hypnotic dose of sodium pentobarbital induced-sleeping [the ED50+/-95% LC value was 21.06+/-3.04 mg/kg]. CPG and R(-)-CPG displayed nearly equipotent effect in depressing oxotremorine-induced salivation [the ED50 +/-95% LC for R(-) and CPG were 1.10+/-0.28 and 1.07+/-0.15 mg/kg, respectively], and the contractile response to carbachol (pA(2) values for R (-) and CPG were 6.84 and 6.80, respectively). S(+)-CPG presented the lowest anticholinergic profiles, but could potentate effects of its enantiomers in some manner. CONCLUSIONS: These data suggested that R(-)-CPG acted as an eutomer in racemate and a competitive antagonist to acetylcholine muscarinic receptors, but S(+)-CPG was less active in comparison to R(-)-CPG and its racemate. The central depressant effects of R(-)-CPG and S(+)-CPG were lower in comparison to its racemate.     

唑来膦酸治疗绝经后骨质疏松症的临床研究

目的 观察唑来膦酸治疗绝经后骨质疏松症(PMOP)的疗效及安全性.方法 选取2009年6月至2009年8月PMOP患者31例,予以唑来膦酸5mg,静脉滴注15 min,同时每天补充钙剂800 mg和活性维生素D0.25μg,疗程1年.测定治疗前后的腰椎2-4、股骨颈与股骨近端骨密度(BMD)值.结果 治疗1年后,腰椎(L2-4)、股骨颈和股骨近端骨密度均较治疗前显著提高(P<0.001),增幅分别为3.6%、2.7%和3.5%.6例患者出现发热、恶心、疼痛等轻到中度流感样症状,3天内缓解.未见明显不良反应.结论 唑来膦酸治疗绝经后骨质疏松症能显著改善患者骨量,临床使用安全、方便.     

唑来膦酸治疗绝经后骨质疏松症的临床研究

目的观察唑来膦酸治疗绝经后骨质疏松症(PMOP)的疗效及安全性。方法选取2009年6月至2009年8月PMOP患者31例,予以唑来膦酸5mg,静脉滴注15 min,同时每天补充钙剂800 mg和活性维生素D 0.25μg,疗程1年。测定治疗前后的腰椎2-4、股骨颈与股骨近端骨密度(BMD)值。结果治疗1年后,腰椎(L2-4)、股骨颈和股骨近端骨密度均较治疗前显著提高(P<0.001),增幅分别为3.6%、2.7%和3.5%。6例患者出现发热、恶心、疼痛等轻到中度流感样症状,3天内缓解。未见明显不良反应。结论唑来膦酸治疗绝经后骨质疏松症能显著改善患者骨量,临床使用安全、方便。