Patent Publication Number: US-2007104661-A1

Title: Compositions for the treatment of affections of the oral cavity and upper respiratory tract

Description:
The present invention relates to compositions containing anthocyanosides and/or procyanidins in combination with floroglucinols for the treatment of the affections of the oral cavity and upper respiratory tract.  
     TECHNOLOGICAL BACKGROUND  
      Throat redness and inflammation, with formation of plaques, usually accompany common influenza, coryza and other cold diseases. Common cold and influenza, which on the average affect up to three times a year both children and adults, are related to mild viral infections caused by rhinovirus (40%), coronavirus (10%) and, to a less extent, adenovirus and parainfluenza viruses. Although no specific treatments exist for these pathologies, antihistamines and decongestants are considered useful, as the edema reduction alleviates pain and makes the course of the disease shorter.  
     DISCLOSURE OF THE INVENTION  
      The present invention relates to compositions containing:  
      a) anthocyanosides, and/or  
      b) procyanidins, and  
      c) floroglucinols,  
      useful for the treatment of the affections of the oral cavity and upper respiratory tract.  
      According to the present invention, the compositions contain 1 to 200 mg of anthocyanosides, and/or 1 to 200 mg of procyanidins, and 1 to 200 mg of floroglucinols.  
      According to the present invention, “anthocyanosides” includes both real anthocyanosides and anthocyanidins, their aglycones. The anthocyanosides preferably are derived from  Vaccinium myrtillus  extracts. The extract of bilberry ( Vaccinium myrtillus ), as described in literature, has marked antiinflammatory activity, in particular topically, due to its action on capillary permeability and fragility. The preparation of bilberry extracts containing anthocyanosides is known to those skilled in the art. Bilberry anthocyanosides and procyanidins exert bacteriostatic action which prevents bacterial and fungal adhesion, for example at the dental and paradental level and on mucous membranes.  
      According to the present invention, the procyanidins can preferably be derived from  Vitis vinifera  extracts, obtained as disclosed in GB 1,541,469, or from  Camellia sinensis  extracts, as disclosed in EP 0 814 823, or from other plants, preferably edible, containing them.  
      Floroglucinols exert strong bacteriostatic action on a great number of bacteria and fungi strains. The minimum inhibitory concentration values of some floroglucinols on gram+ bacteria, gram− anaerobic bacteria and strains of  Candida albicans  range from 0.5 to 4 μg/ml.  
      According to the present invention, floroglucinols can be derived from  Hypericum  spp. extracts, preferably  Hypericum perforatuni , or from  Mirtus  spp. extracts, preferably  Mirtus communis , or from  Humulus  spp. fractions, preferably  Humulus lupulus , enriched in α and β acids. According to the invention, the fraction of β-acids prepared from  Humulus lupulus  contains 20 to 80%, preferably 60%, of floroglucinols expressed as colupulone; the fraction of α-acids contains 20 to 80%, preferably 60%, of humulone.  
      According to the present invention, among the  Hypericum  sp. extracts, particularly preferred is a  Hypericum perforatum  extract with a floroglucinols (adhyperforin/hyperforin) content ranging from 20 to 80%, preferably 60%.  
      According to the present invention, the  Mirtus communis  extract is prepared from the leaves, by extraction with carbon dioxide under conditions of pressure ranging from 235 to 260 bars and temperatures ranging from 40 to 60° C., preferably 45° C. The resulting extract usually has a mirtocumolone content of 35%.  
      The compositions of the invention are capable of preventing the formation of purulent plaques deriving from various saprophytic infections of the oral cavity, thus avoiding the use of antibiotics, while reducing the progress of the infection. In particular, the compositions of the invention proved to exert a synergistic effect mainly as regards the duration of the disease.  
      Furthermore, the compositions of the invention exert favourable action on the cleanliness of the oral cavity and the removal of the dental plaque, thanks to the effect reducing bacterial adhesiveness, as already mentioned, exerted by bilberry extract and procyanidins, and to the high activity of floroglucinols on anaerobic bacterial strains.  
      The pharmaceutical compositions will be preferably presented in the form of tablets for the slow dissolution in the oral cavity or chewing gums which provide the slow release of the active principles. These compositions are used in preventive and prophylactic treatments as well as for the hygiene of the oral cavity.  
      According to a further preferred aspect, the compositions of the present invention will further contain essential oils, in particular mint oil.  
      According to a further preferred aspect, the compositions of the present invention will further contain a  Glycyrrhiza  extract, preferably having a content in glycyrrhizic acid of 10%.  
      The present invention, therefore, relates to compositions for the treatment of the affections of the oral cavity and upper respiratory tract, containing the combinations described above.  
      Said compositions will be prepared according to conventional methods well known in pharmaceutical technique, as those described in “Remington&#39;s Pharmaceutical Handbook”, Mack Publishing Co., N.Y., USA, together with suitable excipients commonly used in the art.  
      The present invention also relates to the use of a combination of anthocyanosides, and/or procyanidins, and floroglucinols, for the preparation of a medicament for the treatment of the affections of the oral cavity and upper respiratory tract.  
      The examples reported hereinbelow further illustrate the invention. 
    
    
     EXAMPLE I  
     Tablets  
     
       
         
           
               
             
               
                   
               
               
                   
               
               
                 Each 500 mg tablet contains: 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
            
               
                   
                   Vaccinium myrtillus  extract (25% in anthocyanidins) 
                 60 mg 
               
               
                   
                   Humulus lupulus  extract (60% in floroglucinols) 
                 10 mg 
               
               
                   
                 Soy lecithin (30% phosphatidylcholine) 
                 30 mg 
               
               
                   
                   Glycyrrhiza  extract (10% of glycyrrhizic acid) 
                 20 mg 
               
               
                   
                 Mint essential oil 
                 10 mg 
               
               
                   
                 Saccharose 
                 200 mg  
               
               
                   
                 Maltodextrin 
                 150 mg  
               
               
                   
                 Acacia gum 
                 15 mg 
               
               
                   
                 Magnesium stearate 
                  5 mg 
               
               
                   
                   
               
            
           
         
       
     
     EXAMPLE II  
     Tablets  
     
       
         
           
               
             
               
                   
               
               
                   
               
               
                 Each 500 mg tablet contains: 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
            
               
                   
                   Vitis vinifera  extract (95% in procyanidins) 
                 80 mg 
               
               
                   
                   Humulus lupulus  extract (60% in floroglucinols) 
                 10 mg 
               
               
                   
                 Soy lecithin (30% phosphatidylcholine) 
                 30 mg 
               
               
                   
                   Glycyrrhiza  extract (10% of glycyrrhizic acid) 
                 20 mg 
               
               
                   
                 Mint essential oil 
                 10 mg 
               
               
                   
                 Mannitol 
                 320 mg  
               
               
                   
                 Povidone 
                 20 mg 
               
               
                   
                 Silicium dioxide 
                  5 mg 
               
               
                   
                 Magnesium stearate 
                  5 mg 
               
               
                   
                   
               
            
           
         
       
     
     EXAMPLE III  
     Tablets  
     
       
         
           
               
             
               
                   
               
               
                   
               
               
                 Each 500 mg tablet contains: 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
            
               
                   Vitis vinifera  extract (95% in procyanidins) 
                 80 mg 
               
               
                   Mirtus communis  lipophilic extract (35% in mirtocupulone) 
                 10 mg 
               
               
                   Glycyrrhiza  extract (10% of glycyrrhizic acid) 
                 20 mg 
               
               
                 Mint essential oil 
                 10 mg 
               
               
                 Maltodextrin 
                 332 mg  
               
               
                 Sodium saccharin 
                  3 mg 
               
               
                 Arabic gum 
                 30 mg 
               
               
                 Talc 
                 10 mg 
               
               
                 Magnesium stearate 
                  5 mg 
               
               
                   
               
            
           
         
       
     
     EXAMPLE IV  
     Tablets  
     
       
         
           
               
             
               
                   
               
               
                   
               
               
                 Each 500 mg tablet contains: 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
            
               
                   Vaccinium myrtillus  extract (25% in anthocyanidins) 
                 60 mg 
               
               
                   Mirtus communis  lipophilic extract (35% in mirtocupulone) 
                 10 mg 
               
               
                 Soy lecithin (30% phosphatidylcholine) 
                 30 mg 
               
               
                   Glycyrrhiza  extract (10% of glycyrrhizic acid) 
                 20 mg 
               
               
                 Mint essential oil 
                 10 mg 
               
               
                 Saccharose 
                 330 mg  
               
               
                 Tragacanth gum 
                 20 mg 
               
               
                 Silicium dioxide 
                  5 mg 
               
               
                 Magnesium stearate 
                  5 mg 
               
               
                   
               
            
           
         
       
     
     EXAMPLE V  
     Tablets  
     
       
         
           
               
             
               
                   
               
               
                   
               
               
                 Each 500 mg tablet contains: 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
            
               
                   Camellia sinensis  extract (70% in procyanidole oligomers) 
                 80 mg 
               
               
                   Humulus lupulus  extract (60% in floroglucinols) 
                 10 mg 
               
               
                 Soy lecithin (30% phosphatidylcholine) 
                 30 mg 
               
               
                   Glycyrrhiza  extract (10% of glycyrrhizic acid) 
                 20 mg 
               
               
                 Mint essential oil 
                 10 mg 
               
               
                 Mannitol 
                 320 mg  
               
               
                 Povidone 
                 20 mg 
               
               
                 Silicium dioxide 
                  5 mg 
               
               
                 Magnesium stearate 
                  5 mg 
               
               
                   
               
            
           
         
       
     
     EXAMPLE VI  
     Tablets  
     
       
         
           
               
             
               
                   
               
               
                   
               
               
                 Each 500 mg tablet contains: 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
            
               
                   Camellia sinensis  extract (70% in procyanidole oligomers) 
                 80 mg 
               
               
                   Hypericum perforatum  extract (60% in floroglucinols) 
                 10 mg 
               
               
                 Soy lecithin (30% phosphatidylcholine) 
                 30 mg 
               
               
                   Glycyrrhiza  extract (10% of glycyrrhizic acid) 
                 20 mg 
               
               
                 Mint essential oil 
                 10 mg 
               
               
                 Mannitol 
                 320 mg  
               
               
                 Povidone 
                 20 mg 
               
               
                 Silicium dioxide 
                  5 mg 
               
               
                 Magnesium stearate 
                  5 mg 
               
               
                   
               
            
           
         
       
     
     EXAMPLE VII  
     Chewing Gum  
     
       
         
           
               
             
               
                   
               
               
                   
               
               
                 Each 2000 mg chewing gum contains: 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
            
               
                   Vitis vinifera  extract (95% in procyanidins) 
                 80 mg 
               
               
                   Mirtus communis  lipophilic extract (30% in mirtocupulone) 
                 10 mg 
               
               
                   Glycyrrhiza  extract (10% of glycyrrhizic acid) 
                 20 mg 
               
               
                 Mint essential oil 
                 10 mg 
               
               
                 Gum base 
                 1598 mg  
               
               
                 Xylitol 
                 250 mg  
               
               
                 Aspartame 
                  2 mg 
               
               
                 Magnesium stearate 
                 15 mg 
               
               
                 Talc 
                 15 mg