Arruzazabala M L, Molina V, Carbajal D, Fernández L, Mas R, Castaño G, Illnait J, Mendoza S, Fernańdez J
Center for Natural Products of the National Center for Scientific Research, Havana City, Cuba.
Int J Clin Pharmacol Res. 2005;25(1):29-39.
D-003 is a mixture of high molecular weight aliphatic primary acids purified from sugar cane wax with antiplatelet and cholesterol-lowering effects. Previous studies showed that D-003 (10-20 mg/day) administered for a short time inhibits platelet aggregation, 14 days being the longest duration investigated. This study was conducted to investigate the effects of D-003 (5 and 10 mg/day) for 30 days on platelet aggregation in normocholesterolemic subjects. This report shows the effects of D-003 on platelet aggregation to arachidonic acid (AA) (1.5 mM), collagen (2 microg/ml) and adenosine 5'-diphosphate ADP (2 microM) assessed at baseline and at treatment completion. Fifty-four subjects were randomized to placebo or D-003 (5 or 10 mg/day) for 30 days. Platelet aggregation to AA, collagen and ADP were assessed. D-003 at the lowest dose (5 mg/day) significantly but modestly inhibited (p < 0.01) platelet aggregation to AA (5.0%) and (p < 0.01) to collagen (7.5%). D-003 at 10 mg/day inhibited (p < 0.001) platelet aggregation to AA and collagen (p < 0.01) by 20.3% and 14.7%, respectively. ADP-induced aggregation, however, was unchanged. D-003 at 10 mg/day, but not at 5 mg/day, lowered (p < 0.01) plasma fibrinogen. D-003 (5 and 10 mg/day) reduced low-density lipoprotein cholesterol (LDL-C) by 17.7% and 26.4%, respectively, and total cholesterol (TC) by 14.5% and 18.5%, while at 10 mg/day, but not at 5 mg/day, it increased high-density lipoprotein cholesterol (HDL-C) by 9.6%. Triglycerides, however, were unchanged with D-003. No disturbances in safety indicators were induced with D-003. One subject (D-003 5 mg/day) discontinued the study and four patients (three taking D-003 and one taking placebo) reported adverse effects (AE) (headache in two patients taking D-003 and one patient taking placebo, and polyphagia in one patient taking D-003). In conclusion, D-003 (5-10 mg/day) for 30 days inhibited platelet aggregation to AA and collagen but not to ADP Therefore, the antiplatelet effect was present with the longer treatment, even at a dose of 5 mg/day. The cholesterol-lowering effects of D-003 were consistent with those expected for such a short treatment. In addition, D-003 at 10 mg/day significantly lowered plasma fibrinogen. The treatment was well tolerated.
D - 003是一种从甘蔗蜡中提纯的高分子量脂肪族一元酸混合物，具有抗血小板和降胆固醇作用。先前的研究表明，短期服用D - 003（10 - 20毫克/天）可抑制血小板聚集，研究的最长持续时间为14天。本研究旨在探讨D - 003（5毫克/天和10毫克/天）连续30天对正常胆固醇水平受试者血小板聚集的影响。本报告展示了在基线和治疗结束时评估的D - 003对花生四烯酸（AA）（1.5毫摩尔）、胶原蛋白（2微克/毫升）和5'-二磷酸腺苷（ADP）（2微摩尔）诱导的血小板聚集的影响。54名受试者被随机分为安慰剂组或D - 003（5毫克/天或10毫克/天）组，为期30天。评估了血小板对AA、胶原蛋白和ADP的聚集情况。最低剂量（5毫克/天）的D - 003显著但适度地抑制了（p < 0.01）血小板对AA的聚集（5.0%）以及（p < 0.01）对胶原蛋白的聚集（7.5%）。10毫克/天的D - 003抑制了（p < 0.001）血小板对AA的聚集以及（p < 0.01）对胶原蛋白的聚集，分别为20.3%和14.7%。然而，ADP诱导的聚集没有变化。10毫克/天的D - 003降低了（p < 0.01）血浆纤维蛋白原水平，但5毫克/天的D - 003未降低。D - 003（5毫克/天和10毫克/天）分别使低密度脂蛋白胆固醇（LDL - C）降低了17.7%和26.4%，总胆固醇（TC）降低了14.5%和18.5%，而10毫克/天的D - 003使高密度脂蛋白胆固醇（HDL - C）升高了9.6%，5毫克/天的D - 003未升高。然而，D - 003对甘油三酯没有影响。D - 003未引起安全指标的紊乱。一名受试者（D - 003 5毫克/天）退出了研究，四名患者（三名服用D - 并报告了不良事件（AE）（两名服用D - 003的患者和一名服用安慰剂的患者出现头痛，一名服用D - 003的患者出现多食）。总之，D - 003（5 - 10毫克/天）连续30天抑制了血小板对AA和胶原蛋白的聚集，但未抑制对ADP的聚集。因此，即使在5毫克/天的剂量下，较长时间治疗也具有抗血小板作用。D - 003的降胆固醇作用与如此短疗程预期的效果一致。此外，10毫克/天的D - 003显著降低了血浆纤维蛋白原水平。该治疗耐受性良好。
