VS-501: A NOVEL, NON-ABSORBED, CALCIUM- AND ALUMINUM-FREE, HIGHLY EFFECTIVE PHOSPHATE BINDER DERIVED FROM NATURAL PLANT POLYMER.
VS-501: A NOVEL, NON-ABSORBED, CALCIUM- AND ALUMINUM-FREE, HIGHLY EFFECTIVE PHOSPHATE BINDER DERIVED FROM NATURAL PLANT POLYMER.
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VS-501：一种新型、不被吸收、不含钙和铝、高效磷酸盐粘合剂，源自天然植物聚合物。
DOI：
10.1002/prp2.42
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发表时间：
2014
影响因子：
2.6
通讯作者：
Wessale,JerryL
中科院分区：
文献类型：
--
作者：
Wu-Wong,JRuth;Chen,Yung-Wu;Gaffin,Robert;Hall,Andy;Wong,JonathanT;Xiong,Joseph;Wessale,JerryL
慢性肾脏疾病患者血清磷酸盐控制不佳可导致具有临床意义的病理。市售磷结合剂的有效性受到安全性问题的限制，并且由于高药丸尺寸/负担和胃肠道（GI）不适而导致依从性低。VS-501是一种非吸收、不含钙和铝、化学改性的植物源聚合物。体外研究表明，VS-501在暴露于模拟胃液时具有高密度和低溶胀体积（与司维拉姆相比）。当正常饮食的雄性SD大鼠接受VS-501或司维拉姆给药时，血清磷酸盐没有显著改变，但尿磷酸盐水平降低> 90%。VS-501对血清钙（Ca）或尿Ca无影响，而3%司维拉姆可显著增加血清和尿Ca。在接受高磷饮食的5/6肾切除（NX）尿毒症SD大鼠中，增加饮食磷酸盐导致血清和尿磷酸盐增加，这在VS-501或司维拉姆（0.2-5%食物）治疗的大鼠中得到预防。高磷酸盐饮食还增加了5/6只NX大鼠的血清成纤维细胞生长因子-23和甲状旁腺激素，VS-501或司维拉姆可预防这一情况。VS-501或司维拉姆以剂量依赖性方式增加粪便磷酸盐。在5/6只接受5%司维拉姆给药的NX大鼠中观察到更多的主动脉钙化，而VS-501和司维拉姆对心脏参数、纤维化、肠组织学和肠钠依赖性磷酸盐协同转运蛋白基因表达无显著影响。这些结果表明，VS-501可有效结合磷酸盐，对钙稳态无影响，并可能改善药丸负担和GI副作用。
Inadequate control of serum phosphate in chronic kidney disease can lead to pathologies of clinical importance. Effectiveness of on‐market phosphate binders is limited by safety concerns and low compliance due to high pill size/burden and gastrointestinal (GI) discomfort. VS‐501 is a nonabsorbed, calcium‐ and aluminum‐free, chemically modified, plant‐derived polymer. In vitro studies show that VS‐501 has a high density and a low swell volume when exposed to simulated gastric fluid (vs. sevelamer). When male Sprague–Dawley (SD) rats on normal diet were treated with VS‐501 or sevelamer, serum phosphate was not significantly altered, but urinary phosphate levels decreased by >90%. VS‐501 had no effect on serum calcium (Ca) or urinary Ca, while 3% sevelamer significantly increased serum and urine Ca. In 5/6 nephrectomized (NX) uremic SD rats on high‐phosphate diet, increasing dietary phosphate led to an increase in serum and urine phosphate, which was prevented in rats treated with VS‐501 or sevelamer (0.2–5% in food). High‐phosphate diet also increased serum fibroblast growth factor‐23 and parathyroid hormone in 5/6 NX rats that was prevented by VS‐501 or sevelamer. VS‐501 or sevelamer increased fecal phosphate in a dose‐dependent manner. More aortic calcification was observed in 5/6 NX rats treated with 5% sevelamer, while VS‐501 and sevelamer did not show significant effects on cardiac parameters, fibrosis, intestine histology, and intestinal sodium‐dependent phosphate cotransporter gene expression. These results suggest that VS‐501 is effective in binding phosphate with no effects on calcium homeostasis, and may have improved pill burden and GI side effects.