Compositions and methods for the treatment or prevention of inflammation

Abstract

The present invention relates to compounds containing as active ingredients hyaluronic acid and polyvinylpyrrolidone, for the treatment of inflammatory, ulcerative and painful conditions of moist epithelial surfaces such as mucositis, stomatitis, vestibulitis, aphthous ulcerations, and Behcet's syndrome.

What is claimed is:  
     
         1 . A composition, comprising: 
 from about 0.01 to about 5 percent by weight of hyaluronic acid, or a pharmaceutically acceptable salt thereof, having a molecular weight from about 1.6 and 2.2 million daltons;    from about 0.04 to about 15% by weight of a K60 to K100 polyvinylpyrrolidone; and    from about 86 to about 98% water,    wherein the viscosity of the composition is from about 50 to about 500 centipoise.    
     
     
         2 . The composition of  claim 1 , wherein the polyvinylpyrrolidone is from about K85 to about K95 and is from about 3 to about 10% by weight of the composition.  
     
     
         3 . The composition of  claim 2 , wherein the polyvinylpyrrolidone is from about 7 to about 10% by weight of the composition.  
     
     
         4 . The composition of  claim 1 , wherein the hyaluronic acid, or the pharmaceutically acceptable salt thereof, is from about 1.8 to about 2.0 million daltons, and from about 0.01 to about 2% by weight of the composition, and wherein the viscosity of the composition is from about 90 to about 1000 centipoise.  
     
     
         5 . The composition of  claim 4 , in the form of a gel.  
     
     
         6 . The composition of  claim 3 , wherein the hyaluronic acid, or the pharmaceutically acceptable salt thereof, is from about 1.8 to about 2.0 million daltons and from about 0.01% to about 2% by weight of the composition, and wherein the viscosity of the composition is from about 90 to about 1000 centipoise.  
     
     
         7 . The composition of  claim 6 , in the form of a gel.  
     
     
         8 . The composition of  claim 1 , further comprising a viscosity-increasing agent, surfactant, stabilizing agent/preservative, flavour, fragrance, sweetening agent, bioadhesive agent, or a co-solubilizer.  
     
     
         9 . The composition of  claim 8 , further comprising a cellulose derivative, acrylic or methacrylic acid polymer or copolymer, ethylene or propylene glycol, polyethoxylated hydrogenated castor oil, EDTA, sodium benzoate, sodium or potassium sorbate, dextrin, sodium saccharin, or aspartame.  
     
     
         10 . The composition of  claim 1 , further comprising an antibacterial agent, disinfectant agent, antifungal agent, analgesic, anti-inflammatory, emollient, or a local anesthetic.  
     
     
         11 . The composition of  claim 1 , further comprising glycyrrhetinic acid or a pharmaceutically acceptable salt thereof.  
     
     
         12 . A composition comprising: 
 from about 0.04 to about 5 percent by weight of hyaluronic acid, or a pharmaceutically acceptable salt thereof, with a molecular weight from about 1.6 to about 2.2 million daltons;    from about 0.08 to about 15% by weight of a K60 to K100 polyvinylpyrrolidone; and    from about 86 to about 98% water,    wherein the viscosity of the composition is from about 50 to about 500 centipoise.    
     
     
         13 . The composition of  claim 12 , wherein the polyvinylpyrrolidone is from about K85 to about K95, and is from about 6 to about 12% by weight of the composition.  
     
     
         14 . The composition of  claim 13 , wherein the polyvinylpyrrolidone is from about 8 to about 10% by weight of the composition.  
     
     
         15 . The composition of  claim 12 , wherein the hyaluronic acid, or the pharmaceutically acceptable salt thereof, is from about 1.8 to about 2.0 million daltons and from about 0.04 to about 2% by weight of the composition.  
     
     
         16 . The composition of  claim 15 , in the form of a gel.  
     
     
         17 . The composition of  claim 14 , wherein the hyaluronic acid, or the pharmaceutically acceptable salt thereof, is from about 1.8 to about 2.0 million daltons and from about 0.04 to about 2% by weight of the composition.  
     
     
         18 . The composition of  claim 17 , in the form of a gel.  
     
     
         19 . The composition of  claim 12 , further comprising a viscosity-increasing gent, surfactant, stabilizing agent/preservative, flavour, fragrance, sweetening agent, bioadhesive agent, or a co-solubilizer.  
     
     
         20 . The composition of  claim 19 , further comprising a cellulose derivative, acrylic or methacrylic acid polymer or copolymer, ethylene or propylene glycol, polyethoxylated hydrogenated castor oil, EDTA,.sodium benzoate, sodium or potassium sorbate, dextrin, sodium saccharin, or aspartame.  
     
     
         21 . The composition of  claim 12 , further comprising an antibacterial agent, disinfectant agent, antifungal agent, analgesic, anti-inflammatory, emollient, or a local anesthetic.  
     
     
         22 . The composition of  claim 12 , further comprising glycyrrhetinic acid or a pharmaceutically acceptable salt thereof.  
     
     
         23 . A flexible packet comprising the composition of  claim 12 .  
     
     
         24 . The packet of  claim 23 , being a sealed pouch comprising from about 10 to about 30 milliliters of the composition.  
     
     
         25 . A composition comprising hyaluronic acid or a pharmaceutically acceptable salt thereof; glycyrrhetinic acid or a pharmaceutically acceptable salt thereof; and polyvinylpyrrolidone.  
     
     
         26 . A flexible packet comprising the composition of  claim 25 .  
     
     
         27 . The composition of  claim 25 , further comprising a viscosity-increasing gent, surfactant, stabilizing agent/preservative, flavour, fragrance, sweetening agent, bioadhesive agent, or a co-solubilizer.  
     
     
         28 . The composition of  claim 27 , further comprising a cellulose derivative, acrylic or methacrylic acid polymer or copolymer, ethylene or propylene glycol, polyethoxylated hydrogenated castor oil, EDTA, sodium benzoate, sodium or potassium sorbate, dextrin, sodium saccharin, or aspartame.  
     
     
         29 . The composition of  claim 25 , further comprising an antibacterial agent, disinfectant agent, antifungal agent, analgesic, anti-inflammatory, emollient, or a local anesthetic.  
     
     
         30 . A method for treating or preventing inflammation in a patient comprising: 
 administering to a patient in need thereof an effective amount of a composition comprising: 
 (i) from about 0.01 to about 5 percent by weight of hyaluronic acid, or a pharmaceutically acceptable salt thereof, having a molecular weight from about 1.6 to about 2.2 million daltons;  
 (ii) from about 0.04 to about 15% by weight of a K60 to K100 polyvinylpyrrolidone; and  
 (iii) from about 86 to about 98% water,  
 wherein the viscosity of the composition is from about 50 to about 500 centipoise.  
   
     
     
         31 . The method of  claim 30 , wherein the composition is administered at least twice daily for at least two consecutive days.  
     
     
         32 . The method of  claim 30 , wherein the composition is administered at least three times daily for at least four consecutive days.  
     
     
         33 . The method of  claim 30 , wherein the composition is administered at least three times daily for at least seven consecutive days.  
     
     
         34 . The method of  claim 30 , wherein the composition further comprises a viscosity-increasing agent, surfactant, stabilizing agent/preservative, flavour, fragrance, sweetening agent, bioadhesive agent, or a co-solubilizer.  
     
     
         35 . The method of  claim 34 , wherein the composition further comprises a cellulose derivative, acrylic or methacrylic acid polymer or copolymer, ethylene or propylene glycol, polyethoxylated hydrogenated castor oil, EDTA, sodium benzoate, sodium or potassium sorbate, dextrin, sodium saccharin, or aspartame.  
     
     
         36 . The method of  claim 30 , wherein the composition further comprises an antibacterial agent, disinfectant agent, antifungal agent, analgesic, anti-inflammatory, emollient, or a local anesthetic.  
     
     
         37 . The method of  claim 30 , wherein the administration is by topical application.  
     
     
         38 . The method of  claim 30 , wherein the composition further comprises glycyrrhetinic acid or a pharmaceutically acceptable salt thereof.  
     
     
         39 . A method for treating or preventing inflammation in a patient, comprising administering to a patient in need thereof an effective amount of a composition comprising hyaluronic acid or a pharmaceutically acceptable salt thereof; glycyrrhetinic acid or a pharmaceutically acceptable salt thereof; and polyvinylpyrrolidone.  
     
     
         40 . The method of  claim 39 , wherein the administration is by topical application.  
     
     
         41 . The method of  claim 39 , wherein the composition is administered at least twice daily for at least two consecutive days.  
     
     
         42 . The method of  claim 39 , wherein the composition is administered at least three times daily for at least four consecutive days.  
     
     
         43 . The method of  claim 39 , wherein the composition is administered at least three times daily for at least seven consecutive days.  
     
     
         44 . The method of  claim 39 , wherein the composition further comprises a viscosity-increasing agent, surfactant, stabilizing agent/preservative, flavour, fragrance, sweetening agent, bioadhesive agent, or a co-solubilizer.  
     
     
         45 . The method of  claim 44 , wherein the composition further comprises a cellulose derivative, acrylic or methacrylic acid polymer or copolymer, ethylene or propylene glycol, polyethoxylated hydrogenated castor oil, EDTA, sodium benzoate, sodium or potassium sorbate, dextrin, sodium saccharin, or aspartame.  
     
     
         46 . The method of  claim 39 , wherein the composition further comprises an antibacterial agent, disinfectant agent, antifungal agent, analgesic, anti-inflammatory, emollient, or a local anesthetic.  
     
     
         47 . A method for treating or preventing inflammation in the oral cavity of a patient comprising: 
 having a patient in need thereof gargle an effective amount of a composition comprising: 
 (i) from about 0.01 to about 5 percent by weight of hyaluronic acid, or a pharmaceutically acceptable salt thereof, having a molecular weight from about 1.6 to about 2.2 million daltons;  
 (ii) from about 0.04 to about 15% by weight of a K60 to K100 polyvinylpyrrolidone; and  
 (iii) from about 86 to about 98% water,  
 wherein the viscosity of the composition is from about 50 to about 500 centipoise.  
   
     
     
         48 . A method for treating or preventing inflammation in the oral cavity of a patient comprising: 
 having a patient in need thereof gargle an effective amount of a composition comprising hyaluronic acid or a pharmaceutically acceptable salt thereof; glycyrrhetinic acid or a pharmaceutically acceptable salt thereof; and polyvinylpyrrolidone.    
     
     
         49 . The method of  claim 47  or  48 , wherein the patient gargles the composition at least twice daily for at least two consecutive days.  
     
     
         50 . The method of  claim 47  or  48 , wherein the patient gargles the composition at least three times daily for at least four consecutive days.  
     
     
         51 . The method of  claim 47  or  48 , wherein the patient gargles the composition at least three times daily for at least seven consecutive days.  
     
     
         52 . The method of  claim 47 , wherein the composition further comprises glycyrrhetinic acid or a pharmaceutically acceptable salt thereof.  
     
     
         53 . The method of  claim 47  or  48 , wherein the patient avoids eating or drinking for at least one hour after gargling.  
     
     
         54 . A method for treating or preventing mucositis in a patient comprising: 
 administering to a patient in need thereof an effective amount of a composition comprising: 
 (i) from about 0.01 to about 5 percent by weight of hyaluronic acid, or a pharmaceutically acceptable salt thereof, having a molecular weight from about 1.6 to about 2.2 million daltons;  
 (ii) from about 0.04 to about 15% by weight of a K60 to K100 polyvinylpyrrolidone; and  
 (iii) from about 86 to about 98% water,  
 wherein the viscosity of the composition is from about 50 to about 500 centipoise.  
   
     
     
         55 . A method for treating or preventing mucositis in a patient comprising: 
 administering to a patient in need thereof an effective amount of a composition comprising hyaluronic acid or a pharmaceutically acceptable salt thereof; glycyrrhetinic acid or a pharmaceutically acceptable salt thereof; and polyvinylpyrrolidone.    
     
     
         56 . The method of  claim 54  or  55 , wherein the composition is administered at least twice daily for at least two consecutive days.  
     
     
         57 . The method of  claim 54  or  55 , wherein the composition is administered at least three times daily for at least four consecutive days.  
     
     
         58 . The method of  claim 54  or  55 , wherein the composition is administered at least three times daily for at least seven consecutive days.  
     
     
         59 . The method of  claim 54 , wherein the composition further comprises glycyrrhetinic acid or a pharmaceutically acceptable salt thereof.  
     
     
         60 . A method for treating pain resulting from oral surgery in a patient in need thereof comprising: 
 having a patient in need thereof gargle an effective amount of a composition comprising: 
 (i) from about 0.01 to about 5 percent by weight of hyaluronic acid, or a pharmaceutically acceptable salt thereof, having a molecular weight from about 1.6 to about 2.2 million daltons;  
 (ii) from about 0.04 to about 15% by weight of a K60 to K100 polyvinylpyrrolidone; and  
 (iii) from about 86 to about 98% water,  
 wherein the viscosity of the composition is from about 50 to about 500 centipoise.  
   
     
     
         61 . A method for treating pain resulting from oral surgery in a patient in need thereof comprising: 
 having a patient in need thereof gargle an effective amount of a composition comprising hyaluronic acid or a pharmaceutically acceptable salt thereof; glycyrrhetinic acid or a pharmaceutically acceptable salt thereof; and polyvinylpyrrolidone.    
     
     
         62 . The method of  claim 60  or  61 , wherein the patient gargles the composition at least twice daily for at least two consecutive days.  
     
     
         63 . The method of  claim 60  or  61 , wherein the patient gargles the composition at least three times daily for at least four consecutive days.  
     
     
         64 . The method of  claim 60  or  61 , wherein the patient gargles the composition at least three times daily for at least seven consecutive days.  
     
     
         65 . The method of  claim 60 , wherein the composition further comprises glycyrrhetinic acid or a pharmaceutically acceptable salt thereof.