Methods and topical formulations for treating inflammation

Abstract

Methods and formulations are provided for the treatment of localized edema, particularly localized edema resulting from chronic venous insufficiency. A metal ion sequestrant is topically administered to a subject afflicted with localized edema in combination with a permeation enhancer selected from methylsulfonylmethane and a combination of methylsulfonylmethane and dimethylsulfoxide. Topically administrable formulations for use in the aforementioned method are also provided.

What is claimed is: 
     
         1 . A method for treating localized edema in a patient, the method comprising: topically applying to the patient at the site of the localized edema a therapeutically effective amount of a metal ion sequestrant and an effective permeation-enhancing amount of a permeation enhancer selected from methylsulfonylmethane and a combination of methylsulfonylmethane and dimethylsulfoxide. 
     
     
         2 . The method of  claim 1 , wherein the localized edema is caused by or associated with an inflammatory condition. 
     
     
         3 . The method of  claim 1 , wherein the localized edema is caused by chronic venous insufficiency. 
     
     
         4 . The method of  claim 1 , wherein the permeation enhancer is methylsulfonylmethane. 
     
     
         5 . The method of  claim 1 , wherein the metal ion sequestrant sequesters ion cations. 
     
     
         6 . The method of  claim 1 , wherein the metal ion sequestrant sequesters calcium cations. 
     
     
         7 . The method of  claim 5 , wherein the metal ion sequestrant additionally sequesters calcium ions. 
     
     
         8 . The method of  claim 1 , wherein the metal ion sequestrant is ethylenediamine tetraacetic acid (EDTA) or a pharmacologically acceptable salt thereof. 
     
     
         9 . The method of  claim 4 , wherein the metal ion sequestrant is ethylenediamine tetraacetic acid (EDTA) or a pharmacologically acceptable salt thereof. 
     
     
         10 . The method of  claim 1 , further comprising topically applying a therapeutically effective amount of an anti-inflammatory agent to the patient at the site of the localized edema. 
     
     
         11 . The method of  claim 1 , wherein the metal ion sequestrant and the permeation enhancer are contained in a single formulation. 
     
     
         12 . The method of  claim 11 , wherein the formulation is selected from a lotion, a cream, and a gel. 
     
     
         13 . The method of  claim 12 , wherein the formulation is a lotion or a cream. 
     
     
         14 . A topically administrable formulation for the treatment of localized edema, comprising a therapeutically effective amount of a metal ion sequestrant, an effective permeation enhancing amount of a permeation enhancer selected from methylsulfonylmethane and a combination of methylsulfonylmethane and dimethylsulfoxide, and a pharmaceutically acceptable topical carrier, wherein the formulation comprises a lotion, cream, or gel. 
     
     
         15 . The formulation of  claim 1 , wherein the permeation enhancer is methylsulfonylmethane. 
     
     
         16 . The formulation of  claim 1 , wherein the metal ion sequestrant sequesters ion cations. 
     
     
         17 . The formulation of  claim 1 , wherein the metal ion sequestrant sequesters calcium cations. 
     
     
         18 . The formulation of  claim 16 , wherein the metal ion sequestrant additionally sequesters calcium ions. 
     
     
         19 . The formulation of  claim 1 , wherein the metal ion sequestrant is ethylenediamine tetraacetic acid (EDTA) or a pharmacologically acceptable salt thereof. 
     
     
         20 . The formulation of  claim 15 , wherein the metal ion sequestrant is ethylenediamine tetraacetic acid (EDTA) or a pharmacologically acceptable salt thereof. 
     
     
         21 . The formulation of  claim 14 , wherein the molar ratio of the permeation enhancer to the metal ion sequestrant is in the range of about 2:1 to about 12:1. 
     
     
         22 . The formulation of  claim 21 , wherein the molar ratio of the permeation enhancer to the metal ion sequestrant in the range of about 4:1 to about 10:1. 
     
     
         23 . The formulation of  claim 14 , wherein the metal ion sequestrant represents approximately 0.6 wt. % to about 10.0 wt. % of the formulation. 
     
     
         24 . The formulation of  claim 14 , wherein the metal ion sequestrant represents approximately 1.0 wt. % to about 5.0 wt. % of the formulation. 
     
     
         25 . The formulation of  claim 14 , wherein the permeation enhancer represents approximately 1 wt. % to about 8 wt. % of the formulation. 
     
     
         26 . The formulation of  claim 14 , further including a therapeutically effective amount of an anti-inflammatory agent.