Walker L A, Watson E S, elSohly M A
Research Institute of Pharmaceutical Sciences, University of Mississippi, University 38677, USA.
Immunopharmacol Immunotoxicol. 1995 Aug;17(3):565-76. doi: 10.3109/08923979509016387.
Studies were carried out in guinea pigs to evaluate the potential for single dose hyposensitization to poison ivy urushiol dermatitis. Sensitization was induced by topical application of 1 mg of poison ivy urushiol to the back of the neck. In the first series of studies, three different analogs of poison ivy urushiol were studied: 1) a mixture of pentadecyl and heptadecyl catechols (PDC/HDC), the saturated side chain analog of the natural urushiol mixture; 2) a mixture of the diacetate esters of PDC and HDC (PDC/HDC Ac), the esterified form of the saturated sidechain analogs; 3) 2-n-pentadecyl hydroquinone diacetate (HQ Ac). Each of these compounds was administered as 5 mg of the free catechol i.m. each week for three weeks. A vehicle group received only corn oil injections. Reactivity to poison ivy urushiol (PIU) challenge was evaluated in skin tests at 1 and 5 weeks post-treatment. PDC/HDC Ac induced a marked reduction in both the incidence and the severity of lesions induced by PIU at both 1 and at 5 weeks post-treatment. Other analogs were ineffective at 5 weeks post-treatment, and were less effective than PDC/HDC Ac at 1 week post-treatment. In a second series of experiments, the efficacy of PDC/HDC Ac was evaluated in both single and multiple dose regiments. One treatment group received 5 mg of PDC/HDC Ac intramuscularly each week for 4 weeks, while another treatment group received a single dose of 20 mg PDC/HDC Ac i.m. Corresponding vehicle control groups were also included. At 1 week post-treatment in the single dose group, the PDC/HDC Ac was only modestly effective, with some reduction of severity of lesions at the higher challenge doses of PIU. However, at 4 and 7 weeks post-treatment, both the incidence and the severity of the lesions at all challenge doses were reduced. In the multiple dose group, the incidence and severity of lesions are reduced at 1 week and 4 weeks post-treatment (4 weeks and 7 weeks after the initial dose) but were not significantly different from the single dose group. These findings indicate that the diacetate ester of PDC/HDC is an effective hyposensitizer to poison ivy urushiol, and that this hyposensitization can be reasonably accomplished in a single dose treatment regimen.
在豚鼠身上进行了多项研究，以评估单次剂量低敏治疗对毒漆树漆酚性皮炎的潜在效果。通过在豚鼠颈部背部局部涂抹1毫克毒漆树漆酚来诱导致敏。在第一系列研究中，对毒漆树漆酚的三种不同类似物进行了研究：1）十五烷基儿茶酚和十七烷基儿茶酚的混合物（PDC/HDC），天然漆酚混合物的饱和侧链类似物；2）PDC和HDC的二乙酸酯混合物（PDC/HDC Ac），饱和侧链类似物的酯化形式；3）2-正十五烷基对苯二酚二乙酸酯（HQ Ac）。每种化合物均以5毫克游离儿茶酚的剂量每周肌肉注射一次，共注射三周。一个赋形剂组仅接受玉米油注射。在治疗后1周和5周的皮肤试验中评估对毒漆树漆酚（PIU）激发的反应性。PDC/HDC Ac在治疗后1周和5周均显著降低了PIU诱导的损伤的发生率和严重程度。其他类似物在治疗后5周无效，且在治疗后1周比PDC/HDC Ac效果差。在第二系列实验中，评估了PDC/HDC Ac在单剂量和多剂量方案中的疗效。一个治疗组每周肌肉注射5毫克PDC/HDC Ac，共4周，而另一个治疗组接受单次剂量20毫克的PDC/HDC Ac肌肉注射。相应的赋形剂对照组也包括在内。在单剂量组治疗后1周，PDC/HDC Ac仅具有适度的效果，在较高剂量的PIU激发下，损伤严重程度有所降低。然而，在治疗后4周和7周，所有激发剂量下的损伤发生率和严重程度均降低。在多剂量组中，治疗后1周和4周（初始剂量后4周和7周）损伤的发生率和严重程度降低，但与单剂量组无显著差异。这些发现表明，PDC/HDC的二乙酸酯是一种有效的毒漆树漆酚低敏剂，并且这种低敏作用可以通过单剂量治疗方案合理实现。
