Therapeutic uses of berberine formulations

Abstract

Uses of pharmaceutical compositions comprising berberine for treatment of dermatologic toxicities and other skin disorders.

1 . A method of treating and/or preventing dermatologic toxicities induced by targeted therapy and/or immunotherapy comprising administering to a patient in need thereof a pharmaceutically effective amount of berberine or a biologically equivalent analogue thereof. 
     
     
         2 . The method according to  claim 1 , wherein said targeted therapy is selected from the group consisting of EGFR inhibitors, multityrosine kinase (MTK) inhibitors, MEK inhibitors, phosphoinositide 3-kinase (PI3K) inhibitors, protein kinase B (AKT) inhibitors, BRAF inhibitors, HER2 inhibitors, multikinase angiogenesis inhibitors, mTOR inhibitors, ALK/c-met inhibitors, multikinase Abl inhibitors, BTK inhibitors, HDAC inhibitors, proteasome inhibitors, and RXR agonists. 
     
     
         3 . The method according to  claim 1 , wherein said immunotherapy is selected from the group consisting of cancer vaccines, cytokine agents, cell therapies, immune checkpoint protein inhibitors, and immune checkpoint protein stimulators. 
     
     
         4 . The method according to  claim 1 , wherein said dermatologic toxicity is selected from the group consisting of papulopustular rash, maculopapular rash, erythema, telangiectasias flushing, paronychia and fissure, hair changes, xerosis, mucositis, pruritus, and hand-foot skin reaction. 
     
     
         5 . The method according to  claim 1 , wherein the biologically equivalent analogue of berberine is selected from the group consisting of jatrorrhizine, palmatine, coptisine, 9-demethylberberine, 9-demethylpalmatine, 13-hydroyberberine, berberrubine, palmatrubine, 9-O-ethylberberrubine, 9-O-ethyl-13-ethylberberrubine, 13-methyldihydroberberine N-methyl salt, tetrahydroprotoberberines and N-methyl salts thereof, and 9-lauroylberberrubine chloride. 
     
     
         6 . The method according to  claim 1 , wherein the biologically equivalent analogue of berberine is palmatine or coptisine. 
     
     
         7 . A method of treating and/or preventing dermatologic toxicities induced by targeted therapy and/or immunotherapy comprising topically applying to affected skin a pharmaceutically effective amount of a topical pharmaceutical composition comprising berberine or a biologically equivalent analogue thereof. 
     
     
         8 . The method according to  claim 7 , wherein said targeted therapy is selected from the group consisting of EGFR inhibitors, multityrosine kinase (MTK) inhibitors, MEK inhibitors, phosphoinositide 3-kinase (PI3K) inhibitors, protein kinase B (AKT) inhibitors, BRAF inhibitors, HER2 inhibitors, multikinase angiogenesis inhibitors, mTOR inhibitors, ALK/c-met inhibitors, multikinase Abl inhibitors, BTK inhibitors, HDAC inhibitors, proteasome inhibitors, and RXR agonists. 
     
     
         9 . The method according to  7 , wherein said immunotherapy is selected from the group consisting of cancer vaccines, cytokine agents, interferons, interleukin-2, cell therapies, immune checkpoint protein inhibitors, and immune checkpoint protein stimulators. 
     
     
         10 . The method according to  claim 7 , wherein said dermatologic toxicity is selected from the group consisting of papulopustular rash, maculopapular rash, erythema, telangiectasias flushing, paronychia and fissure, hair changes, xerosis, mucositis, pruritus, and hand-foot skin reaction. 
     
     
         11 . The method according to  claim 7 , wherein the biologically equivalent analogue of berberine is selected from the group consisting of jatrorrhizine, palmatine, coptisine, 9-demethylberberine, 9-demethyipalmatine, 13-hydroyberberine, berberrubine, palmatrubine, 9-O-ethylberberrubine, 9-O-ethyl-13-ethylberberrubine, 13-methyldihydroerberine N-methyl salt, tetrahydroprotoberberines and N-methyl salts thereof, and 9-lauroylberberrubine chloride. 
     
     
         12 . The method according to  claim 7 , wherein the biologically equivalent analogue of berberine is palmatine or coptisine. 
     
     
         13 . The method according to  claim 7 , wherein the topical pharmaceutical composition comprises at least 0.02% w/w of berberine or a biologically equivalent analogue thereof. 
     
     
         14 . The method according to  claim 7 , wherein the topical pharmaceutical composition comprises about 0.1% to about 2% w/w of berberine or a biologically equivalent analogue thereof. 
     
     
         15 . The method according to  claim 7 , wherein berberine or the biologically equivalent analogue of berberine is the primary pharmaceutically acceptable active component. 
     
     
         16 . The method according to  claim 7 , wherein berberine or the biologically equivalent analogue of berberine is the only pharmaceutically acceptable active component. 
     
     
         17 . The method according to  claim 7 , wherein the topical pharmaceutical composition is in the form of a lotion, cream, ointment, paste, gel, spray, suspension, emulsion, foam, patch, powder and liniment.