Xiong Fei, Wang Hao, Geng Kun-kun, Gu Ning, Zhu Jia-bi
Southeast University, Nanjing, PR China.
Chem Pharm Bull (Tokyo). 2010 Nov;58(11):1455-60. doi: 10.1248/cpb.58.1455.
Breviscapine is a Traditional Chinese Medicine treating cardiovascular diseases by promoting blood circulation and removing blood stasis. The major active component of breviscapine has low aqueous solubility, poor chemical stability, short biological half-life and rapid elimination rate from the plasma. The use of a lipid emulsion formulation containing breviscapine might improve chemical stability, increase drug loading, exhibit sustained release profile. In the present study, we developed an optimized formulation and technological method for the preparation of sterile and stable breviscapine lipid emulsion (Bre-LE) for intravenous infusion. The average particle size, polydispersity index, zeta potential, stability constant (K(s)) value and content of final product were (225.3±8.8) nm, 0.221±0.020, (-29.6±1.5) mV, (24.3±2.9)% and (94.5±0.6)% respectively (n=3). The results of in vitro release experiment suggest that lipid emulsion as breviscapine carrier showed a desirable sustained release profile. Dilution stability and long-term stability were also researched in the present paper. The results show the carrier could protect drug from degradation after dilution by phosphate buffered saline and fetal calf serum. And Bre-LE was stable for up to 6 months at room temperature storage condition. The biodistribution of drug in heart of mice increased dramatically after encapsulation into lipid emulsion which was beneficial to heart disease therapy.
灯盏花素是一种通过活血化瘀治疗心血管疾病的中药。灯盏花素的主要活性成分水溶性低、化学稳定性差、生物半衰期短且从血浆中消除速率快。使用含灯盏花素的脂质乳剂配方可能会提高化学稳定性、增加药物载量并呈现缓释特性。在本研究中，我们开发了一种优化的配方和技术方法，用于制备用于静脉输注的无菌且稳定的灯盏花素脂质乳剂（Bre-LE）。最终产品的平均粒径、多分散指数、zeta电位、稳定常数（K(s)）值和含量分别为(225.3±8.8) nm、0.221±0.020、(-29.6±1.5) mV、(24.3±2.9)%和(94.5±0.6)%（n = 3）。体外释放实验结果表明，脂质乳剂作为灯盏花素载体呈现出理想的缓释特性。本文还研究了稀释稳定性和长期稳定性。结果表明，该载体可保护药物在经磷酸盐缓冲盐水和胎牛血清稀释后不降解。并且Bre-LE在室温储存条件下可稳定长达6个月。药物包封于脂质乳剂后在小鼠心脏中的生物分布显著增加，这有利于心脏病治疗。
