Kyuki K, Shibuya T, Tsurumi K, Fujimura H
Jpn J Pharmacol. 1983 Feb;33(1):121-32. doi: 10.1254/jjp.33.121.
This study was performed to develop a topical ointment of diclofenac-Na which has a potent anti-inflammatory activity by oral administration. At first, research was carried out on the ointment base which influences the external anti-inflammatory effect of the drug. Ointments of diclofenac-Na were prepared with three kinds of bases: lipophilic, emulsion (cream) and gel bases; and their anti-inflammatory effects were compared. The cream was found to have the most potent effect. Therefore, in the next experiment, an optimum concentration of diclofenac-Na in cream was determined comparing the anti-inflammatory effect among the cream preparations containing 0.5, 0.75, 1.0 and 1.5% of the drug. Obvious effects were observed with the cream containing 1.0% and 1.5% of the drug concentration, and there was no significant difference in the anti-inflammatory activities of these two concentrations. Based on these results, the cream preparation containing 1.0% of diclofenac-Na (DF cream) was adopted as the external ointment of the drug. The anti-inflammatory effect of this cream was compared with that of existing anti-inflammatory ointments, i.e., indomethacin gel (IM gel), bufexamac cream (BM cream) and mobilat ointment (ML ointment). DF cream produced obvious inhibition on increased vascular permeability and on acute edema and remarkable suppression of ultraviolet erythema. These activities of DF cream were similar to those of IM gel and more potent than those of BM cream and ML ointment. The inhibitory effect of DF cream on the proliferation of granulation tissue was almost equal to that of ML ointment and more distinguishable than that of IM gel and BM cream. In adjuvant arthritis, DF cream reduced the swelling remarkably in the treated paw and slightly in the untreated paw. The anti-adjuvant activity of DF cream was equal to that of IM gel and more potent than that of BM cream and ML ointment. In pain to pressure stimulation, an analgesic effect was observed in the early stage of DF cream application, and its activity was slightly stronger than that of the other ointments. These results show that DF cream has an obvious anti-inflammatory effect as an external preparation, and the activity is comparable or superior to that of similar existing anti-inflammatory ointments. This cream may be considered as useful in the clinical field as a topical anti-inflammatory preparation.
本研究旨在开发一种双氯芬酸钠外用软膏，该药物口服时具有强大的抗炎活性。首先，对影响药物外用抗炎效果的软膏基质进行了研究。用三种基质制备了双氯芬酸钠软膏：亲脂性基质、乳剂（乳膏）基质和凝胶基质；并比较了它们的抗炎效果。发现乳膏具有最强的效果。因此，在接下来的实验中，通过比较含0.5%、0.75%、1.0%和1.5%药物的乳膏制剂的抗炎效果，确定了乳膏中双氯芬酸钠的最佳浓度。在药物浓度为1.0%和1.5%的乳膏中观察到明显的效果，并且这两种浓度的抗炎活性没有显著差异。基于这些结果，采用含1.0%双氯芬酸钠的乳膏制剂（DF乳膏）作为该药物的外用软膏。将该乳膏的抗炎效果与现有的抗炎软膏，即吲哚美辛凝胶（IM凝胶）、丁苯羟酸乳膏（BM乳膏）和莫比拉软膏（ML软膏）进行了比较。DF乳膏对血管通透性增加和急性水肿产生了明显的抑制作用，并显著抑制了紫外线红斑。DF乳膏的这些活性与IM凝胶相似，且比BM乳膏和ML软膏更强。DF乳膏对肉芽组织增殖的抑制作用几乎与ML软膏相当，且比IM凝胶和BM乳膏更明显。在佐剂性关节炎中，DF乳膏使治疗侧爪的肿胀明显减轻，并使未治疗侧爪的肿胀略有减轻。DF乳膏的抗佐剂活性与IM凝胶相当，且比BM乳膏和ML软膏更强。在压力刺激疼痛方面，在应用DF乳膏的早期观察到镇痛作用，其活性略强于其他软膏。这些结果表明，DF乳膏作为外用制剂具有明显的抗炎作用，其活性与现有的类似抗炎软膏相当或更优。该乳膏可被认为是临床领域中一种有用的外用抗炎制剂。
