Dagenais Simon, Ogunseitan Oladele, Haldeman Scott, Wooley James R, Zaldivar Frank, Kim Ronald C
Department of Environmental Health, Science, and Policy, University of California, Irvine, USA.
Int J Toxicol. 2006 May-Jun;25(3):171-81. doi: 10.1080/10915810600683218.
Proliferol is an investigational new drug containing lidocaine hydrochloride 0.25%, dextrose 12.5%, glycerin 12.5%, and phenol 1.0% in aqueous solution. Despite extensive previous experience with similar drug solutions administered in humans by intraligamentous injection for chronic musculoskeletal conditions for over 50 years, animal toxicity data are unavailable. A pilot study was conducted to assess acute toxic effects prior to undertaking further assessment of this drug. Test animals were four Sprague-Dawley rats and four Yucatan mini-swine. Rats received injections into lumbar paraspinal muscles, whereas swine received injections into lumbosacral ligaments in an attempt to mirror the method of administration in humans. Two doses were studied equivalent to 1x and 5x the typical human dose. Outcomes measured at 24 h and 14 days included clinical observations, clinical chemistry, hematology, urinalysis, local tolerance, and major organ histopathology. In rats and swine, results from clinical chemistry, hematology, and urinalysis were indicative of acute local inflammation. At the high dose, marked (rats) and moderate (swine) short-term above-normal levels in certain liver enzymes were noted. In rats and swine, local tolerance results were indicative of acute local inflammatory changes in the skin, subcutis, and muscle around the injection sites. In rats and swine, major organ histopathology results did not reveal lesions attributable to the drug and clinical observations were within normal limits. In swine, fibroplasia was noted in deeper muscle tissues after 14 days. Injections of Proliferol in lumbar paraspinal muscles in rats and lumbosacral ligaments in swine elicited a modest acute local inflammatory response with no other indications of local or systemic toxicity.
增殖醇是一种研究性新药，其水溶液含有0.25%的盐酸利多卡因、12.5%的葡萄糖、12.5%的甘油和1.0%的苯酚。尽管在过去50多年里，人们对通过韧带内注射给人类使用类似药物溶液治疗慢性肌肉骨骼疾病有广泛的经验，但尚无动物毒性数据。在对该药物进行进一步评估之前，进行了一项试点研究以评估其急性毒性作用。实验动物为4只斯普拉格-道利大鼠和4只尤卡坦小型猪。大鼠接受腰椎旁肌肉注射，而猪接受腰骶韧带注射，试图模拟人类的给药方法。研究了相当于典型人类剂量1倍和5倍的两种剂量。在24小时和14天时测量的结果包括临床观察、临床化学、血液学、尿液分析、局部耐受性和主要器官组织病理学。在大鼠和猪中，临床化学、血液学和尿液分析的结果表明存在急性局部炎症。在高剂量时，观察到某些肝酶在大鼠中显著（高于正常水平）、在猪中中度（高于正常水平）短期升高。在大鼠和猪中，局部耐受性结果表明注射部位周围的皮肤、皮下组织和肌肉出现急性局部炎症变化。在大鼠和猪中，主要器官组织病理学结果未发现可归因于该药物的病变，临床观察也在正常范围内。在猪中，14天后在较深的肌肉组织中发现了纤维组织增生。在大鼠的腰椎旁肌肉和猪的腰骶韧带中注射增殖醇引发了适度的急性局部炎症反应，没有其他局部或全身毒性的迹象。
