Li Bo, Zhang Congsheng, Zhu Yiru, Sun Pinzhi, Fan Shangrui, Wang Weina, Tian Yanan, Lu Hao
College of Veterinary Medicine, Northwest A&F University, Yangling 712100, China.
Department of Veterinary Physiology and Pharmacology, College of Veterinary Medicine, Texas A&M University, College Station, TX 77843, USA.
Animals (Basel). 2023 Aug 16;13(16):2646. doi: 10.3390/ani13162646.
Swainsonine-containing plants contain swainsonine which has been shown to cause neurological signs and pathological changes in farm animals. It causes a large number of livestock poisonings every year resulting in economic losses to the livestock industry. At present, "Jifang E" is used in the prevention of swainsonine-containing plants poisoning livestock, and the preventive effects have been well-documented. However, "Jifang E" is typically administered in drinking water, making it difficult to control the administered dosage, because of feeding difficulties and it may cause certain side effects that are unique to the water-dissolved powder. To overcome these difficulties, we developed a temperature-sensitive gel for injection and the optimal ratio of each formula of sustained-release injection is P407 (24%), P188 (6%), Vitamin C (1%), PEG4000 (0.5%), and "Jifang E" (10%). Our results suggest that novel formulation makes the micellar system more stable and the particles are uniformly dispersed. Colloidal morphological studies showed that each group formed a homogeneous pore structure after gelling, and the structure became more dense with the addition of "Jifang E". The rheological study shows that "Jifang E" is a pseudoplastic fluid, and the addition of "Jifang E" reduces the viscosity of the formula, which is beneficial to the injection. In vitro and in vivo release rate studies have shown that the effective concentration of "Jifang E" can be maintained for 3 to 5 days. The acute toxicity test in SPF Kunming mice showed that its LD was 828.323 mg/kg, with confidence limits of 676.706-1013.911 mg/kg, which is a safe dosage (LD > 200 mg/kg). There were no observed reactions of muscle irritation or subcutaneous tissue irritation with the dosage used for New Zealand rabbits. In summary, we successfully developed the sustained-release injection formulation of "Jifang E" for the prevention of swainsonine-containing plants poisoning livestock, which provides the basis for subsequent field extension trials and the further study of its detoxification mechanism.
含有苦马豆素的植物含有苦马豆素，已证明其会导致家畜出现神经症状和病理变化。每年都会导致大量家畜中毒，给畜牧业造成经济损失。目前，“复方E”用于预防家畜因食用含苦马豆素的植物而中毒，其预防效果已有充分记录。然而，“复方E”通常通过饮水给药，由于投喂困难，难以控制给药剂量，并且可能会引起水溶粉剂特有的某些副作用。为克服这些困难，我们研发了一种注射用温敏凝胶，缓释注射剂各配方的最佳比例为泊洛沙姆407（24%）、泊洛沙姆188（6%）、维生素C（1%）、聚乙二醇4000（0.5%）和“复方E”（10%）。我们的结果表明，新型制剂使胶束系统更稳定，颗粒均匀分散。胶体形态学研究表明，每组凝胶后均形成均匀的孔结构，随着“复方E”的加入，结构变得更加致密。流变学研究表明，“复方E”是一种假塑性流体，“复方E”的加入降低了配方的粘度，有利于注射。体外和体内释放率研究表明，“复方E”的有效浓度可维持3至5天。SPF级昆明小鼠的急性毒性试验表明，其半数致死量为828.323 mg/kg，置信区间为676.706 - 1013.911 mg/kg，这是一个安全剂量（半数致死量>200 mg/kg）。使用该剂量对新西兰兔进行试验时，未观察到肌肉刺激或皮下组织刺激反应。总之，我们成功研发了用于预防家畜因食用含苦马豆素的植物而中毒的“复方E”缓释注射剂配方，为后续田间推广试验及其解毒机制的进一步研究提供了依据。
