Fu'cupping Physical Permeation-Enhancing Technique Enhances the Therapeutic Efficacy of Corydalis yanhusuo Gel Plaster.

Corydalis yanhusuo, a traditional Chinese medicine, is widely used to treat various pains, and its active ingredients are alkaloids. This study aimed to develop a new type of transdermal gel plaster containing the extract of C. yanhusuo. Studies have shown that Fu'cupping physical permeation-enhancing technique can promote the penetration of alkaloids and improve the efficacy of drugs. A transdermal gel plaster containing the extract of C. yanhusuo was prepared and optimized using an orthogonal experimental design. The skin permeation ability of the gel plaster was studied in vitro, while the anti-inflammatory and analgesic effects of the prepared patch alone or with Fu'cupping physical permeation-enhancing technique were evaluated in a rat model. The formulation of a gel plaster containing C. yanhusuo extract was successfully prepared with an optimized composition consisting of glycerin (15 g), sodium polyacrylate (2 g), silicon dioxide (0.3 g), ethanol (2 g), aluminum oxide (0.1 g), citric acid (0.05 g), the C. yanhusuo extract (3 g), and water (15 g). The cumulative transdermal permeation of dehydrocorydaline, corypalmine, tetrahydropalmatine, and corydaline in 24 h was estimated to be 569.7 ± 63.2, 74.5 ± 13.7, 82.4 ± 17.2, and 38.9 ± 8.1 µg/cm², respectively. The in vitro diffusion of dehydrocorydaline and corydaline followed the zero-order kinetics profile, while that of corypalmine and tetrahydropalmatine followed a Higuchi equation. The prepared gel plaster significantly reduced paw swelling, downregulated inflammatory cytokines, and mitigated pain induced by mechanical or chemical stimuli. The Fu'cupping physical permeation-enhancing technique further improved the anti-inflammatory and analgesic effects of the patch. The combined application of the Fu'cupping physical permeation-enhancing technique and the alkaloid gel plaster may be effective against inflammation and pain.