Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P20366 (substance P)
 21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hyaluronan (HA) in combination with diclofenac is currently undergoing clinical trials as a topical preparation in the management of osteoarthritic pain, basal-cell carcinoma and actinic keratosis. These are clearly diverse pathologies, but in all cases substance P plays a central role either directly or through secondary mediators such as prostaglandin E2 and nitric oxide. A common mechanism for HA in combination with diclofenac in these conditions may be through ameliorating the direct and indirect effects of substance P. Additionally, HA appears to depot and hold diclofenac in the epidermis, thereby prolonging its pharmacokinetic half-life. In rabbits, stenosis following balloon angioplasty is prevented by a subcutaneous dose of HA, probably through blockade of cell-surface HA receptors (ICAM-1, CD44 & RHAMM). The physicochemical properties of HA, and the binding of HA to HA receptors, suggests that HA will have value as a novel drug delivery system.
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PMID:Hyaluronan as a drug delivery system for diclofenac: a hypothesis for mode of action. 886 45

Topical gel containing 3% diclofenac in 2.5% hyaluronic acid (HYAL CT1101) is used for the treatment of actinic keratosis. In animal models, diclofenac in hyaluronic acid inhibited angiogenesis and induced neovascular regression in inflammatory tissue, and depleted substance P content in snout tissue. Diclofenac delivered in hyaluronic acid appears to accumulate in the epidermis of human skin in vitro and mice in vivo. Results of clinical trials indicate that topical HYAL CT1101 is effective in the treatment of actinic keratosis. A clinical cure (all lesions fully resolved) was seen in 47% of 108 patients using HYAL CT1101 compared with 19% of patients using placebo after 3 months in 1 randomised, double-blind study. Mild to moderate skin irritation has been reported in up to 72% of patients treated with HYAL CT1101 in clinical studies.
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PMID:Diclofenac/hyaluronic acid. 1031 44