雷尼酸锶

治疗骨质疏松症药生物活性靶点体外研究体内研究雷尼酸锶试剂级价格

雷尼酸锶

CAS号:135459-87-9
英文名:Strontium ranelate
中文名:雷尼酸锶
CBNumber:CB1838150
分子式:C12H12N2O8SSr
分子量:431.91
MOL File:135459-87-9.mol

雷尼酸锶化学性质

熔点 :>310°C (dec.)
储存条件 :Inert atmosphere,Store in freezer, under -20°C
溶解度 :H2O: soluble1mg/mL, clear (warmed)
形态 :powder
颜色 :white to beige
CAS 数据库 :135459-87-9

安全信息

危险品标志 :Xn
危险类别码 :20/21/22
安全说明 :36/37
危险品运输编号 :3077
WGK Germany :3
RTECS号 :XM7581000
海关编码 :29349990

雷尼酸锶性质、用途与生产工艺

治疗骨质疏松症药雷尼酸锶是一种治疗骨质疏松症的药物，外观为白色至微黄色粉末或结晶性粉末，无臭、微溶于水、几乎不溶于乙醇、易溶于稀盐酸，由法国Servier公司研制开发，2004年11月在爱尔兰首次上市，同年12月在英国上市。日本藤泽制药公司拥有本品在日本的开发、生产和销售权。临床上主要用于治疗和预防绝经后妇女的骨质疏松，显著降低椎骨骨折及髋骨骨折发生的危险。
雷尼酸锶具有抑制骨吸收，促进骨形成的双重药理作用。一方面在成骨细胞富集的细胞中，能增大胶原蛋白与非胶原蛋白的合成，通过增强前成骨细胞的增殖而促进成骨细胞介导的骨形成。另一方面，通过降低破骨细胞分化和再吸收活性，减少骨吸收，从而使得骨更新重新达到平衡，有利于骨形成。
雷奈酸锶主要通过锶原子，发挥其药理作用，锶是一种与钙同族的碱土金属元素，在元素周期表中位于钙的下方。其吸收、分布、排泄与钙相似。口服2g以后。锶的绝对生物利用度为27％。大剂量的锶能使骨矿代谢发生异常，低剂量的锶能增强前成骨细胞复制，增加成骨细胞的数量，刺激骨形成；同时还能降低破骨细胞的活性，减少破骨细胞的数量，降低骨吸收的速率。在动物和人体内研究也得到的结果相吻合。
骨质疏松症（OP）是一种进行性骨骼疾病，其特征为骨密度（BMD）降低和骨组织显微结构发生退行性改变。表现为骨脆性提高和易发生骨折，后者以脊椎、髋部和腕处最为常见。妇女由于在停经后或者接受手术切除卵巢后，体内停止产生能保持骨质强硬的雌激素。因此，原发性OP在停经后或更年期妇女中尤为多见。
目前常用于治疗骨质疏松的药物有两类：一类为抑制破骨细胞活性从而抑制骨吸收的药物，如二膦酸盐、雌激素、降钙素等；第二类为促进成骨细胞活性从而刺激骨形成的药物，目前仅有人重组甲状旁腺素1-34一个产品上市，需要注射给药，药价较高。
生物活性 Strontium Ranelate 是Ranelic acid的锶（II）盐，用于(-)-Desmethoxyverapamil结合到钙离子通道，IC50为0.5 mM。
靶点
Target Value
Calcium channel 0.5 mM

体外研究

Strontium Ranelate (0.1-1 mM; 22 days; Mouse calvaria cells) treatment shows the expression of mRNA for early osteoblast markers (alkaline phosphatase, ALP) is visualized by day 5, while late markers (osteocalcin, OCN) are detectable only by day 15 and beyond.
Strontium Ranelate (0.1-1 mM; 22 days; Mouse calvaria cells) treatment results in significantly increases the mRNA expression of the osteoblastic markers ALP, BSP and OCN at day 22 of MC cell culture.
Strontium Ranelate is found to increase alkaline phosphatase activity and prostaglandin E2 production in a COX-2 dependent manner in murine marrow stromal cells.

RT-PCR

Cell Line:	Mouse calvaria (MC) cells
Concentration:	0.1 mM, 0.3 mM or 1 mM
Incubation Time:	22 days
Result:	The expression of mRNA for early osteoblast markers (ALP) was visualized by day 5, while late markers (OCN) were detectable only by day 15 and beyond.

Western Blot Analysis

Cell Line:	Mouse calvaria (MC) cells
Concentration:	0.1 mM, 0.3 mM or 1 mM
Incubation Time:	22 days
Result:	Significantly increased the mRNA expression of the osteoblastic markers ALP, BSP and OCN at day 22 of MC cell culture.

体内研究

Strontium Ranelate increases bone formation and decreased bone resorption, which results in increased bone mass in the vertebrae of intact adult mice.
In intact adult rats, Strontium Ranelate also increases bone mass, as measured by dual-energy X-ray absorptiometry, in lumbar vertebra and femur, and this is confirmed by histological assessment of trabecular bone volume in the tibial metaphysis.
Strontium Ranelate is found to decrease bone resorption and to increase bone formation in alveolar bone in normal adult monkeys (Macaca fascicularis), which exhibits extensive bone remodeling.
In ovariectomized rats, short-term (3 months) treatment with Strontium Ranelate prevents trabecular bone loss induced by oestrogen deficiency, as demonstrated by bone ash, bone mineral content and histomorphometric analysis in the tibial metaphysis. This effect results from decreased bone resorption while bone formation was maintained. These beneficial effects of Strontium Ranelate on bone mass and microarchitecture in ovariectomized rats are confirmed in long-term experiments. In this long-term study (2 years), the increase in bone mass and microarchitecture induced by Strontium Ranelate results in a marked improvement in bone strength, supporting the beneficial effect of this drug on bone resistance.
用途主要用于治疗和预防绝经后妇女的骨质疏松，显著降低椎骨骨折及髋骨骨折发生的危险。