Effect of topical application of a stable prostacyclin analogue, SM-10902 on wound healing in diabetic mice

The mechanism of wound healing induced by topical application of an ointment containing a new stable prostacyclin analogue, SM-10902 ((+)-methyl[2-[(2R,3aS,4R,5R, 6aS)-octahydro-5-hydroxy-4-[(E)-(3S,5S)-3-hydroxy-5-methyl-1- nonenyl]-2-pentalenyl] ethoxy] acetate), was investigated in the full-thickness wounds of genetically diabetic mice (db/db mice). The db/db mice treated with SM-10902 ointment (1, 10 and 100 micrograms/g) showed greater decrease in wound lesion area not covered with epidermis and fewer complete healing days than those treated with ointment base, and the effects of this prostacyclin analogue were greater than those of lysozyme chloride ointment (50 mg/g, Reflap ointment). SM-10902 ointment increased skin blood flow in the central site of the wound with development of wound healing. Histological evaluation of wounds revealed that SM-10902 ointment increased the capillary number during the early stage of the wound-healing process. These results suggest that SM-10902 ointment promotes wound healing through the stimulation of angiogenesis and the improvement of blood flow in neovascularization of repairing wound and may be useful in the treatment of skin ulcers caused by peripheral circulatory insufficiency.