Abstract:
Anticaries compositions containing phaseolamin and optionally fluorides, anti-inflammatory, soothing, abrasive, antibacterial and bacteriostatic agents in admixture with suitable carriers or excipients.

Description:
FIELD OF THE INVENTION  
       [0001]     The present invention relates to anticaries compositions containing salivar ptyalin inhibitors.  
         [0002]     More particularly, the present invention relates to anticaries compositions containing phaseolamin.  
       STATE OF THE ART  
       [0003]     Dental caries is a destructive process that affects the hard tissues of the tooth. Although its main cause is the acids produced by the bacteria of the dental plaque, other concomitant factors, such as host susceptibility and presence of sugars and cariogenic bacteria, contribute to its development.  
         [0004]     As far as host susceptibility is concerned, tooth structure plays a remarkable role in caries onset. For example, food residues and bacteria tend to settle on teeth carved with deep fissures. Plaque also accumulates on crowded teeth, as narrow interdental spaces cannot be easily reached by the toothbrush. Moreover, some physiological conditions, such as hormonal changes occurring during pregnancy and milking, make the saliva more viscous, thus increasing bacterial adhesiveness to the tooth and susceptibility to caries.  
         [0005]     Sugars are also a major determinant: they are metabolised to acids by certain bacteria usually present in the oral cavity and such acids cause tooth demineralisation and start tooth decay. Caries is caused not only by simple sugars, primarily glucose and saccharose, but also by complex sugars, mainly starch contained in pasta and bread. Starch is a glucose polymer digested in the intestine by pancreatic α-amylase; glucose is subsequently absorbed and the glycemic level increases. Actually, starch digestion does not start in the intestine, but in the oral cavity, through the action of ptyalin, a salivar α-amylase. Ptyalin provides on the tooth surface a considerable amount of simple sugars that are metabolised by the bacteria of the dental plaque into acids responsible for demineralisation. In other words, starch residues (pasta, bread, potatoes and the like) are indirectly responsible for caries onset.  
         [0006]     Among the microbial species found in the mouth (more than 350), the main causes of caries lesions are Streptococcus mutans and lactobacilli; the former, in particular, sticks to the enamel surface and builds up a polysaccharides net to which a number of other microrganisms adhere, thus causing the formation of the so-called “bacterial plaque”.  
         [0007]     A good oral hygiene, through brushing and flossing, is necessary to prevent caries. To remove cariogenic substances and plaque from the oral cavity, teeth should be thoroughly brushed after each meal, in particular before bedtime, because at night food residues are easily metabolised to acids. Nevertheless, good oral hygiene might not be sufficient in the case of individuals having a particular predisposition to caries. Moreover, good oral hygiene (brushing and flossing) cannot be easily maintained during working hours.  
         [0008]     Several attempts have been made for some years to reduce caries incidence, but an effective remedy has not been found to date. Fluorine proved particularly effective: daily assumption of fluorine tablets or drops during tooth mineralization (a process that terminates at the age of 12) makes the enamel more resistant to acids; when mineralisation is complete, systemically-administered fluorine is not able do reach the enamel. On the contrary, topical use of fluorine is effective at any age, as it both reinforces the enamel and inhibits acids production. Fluorine (optionally in combination with chlorhexidine) has also been used for some time in mouthwashes or medicated toothpastes, but their beneficial effects are limited.  
         [0009]     To solve these problems, lacquers that provide targeted, sustained release of small amounts of fluorine or chlorhexidine have been recently put on the market. Thus, susceptible subjects can be treated with products that avoid caries formation, such as sealers and lacquers based on fluorine or chlorhexidine. Sealers are resins which are applied on the chewing surfaces of healthy teeth in order to reduce the depth of the fissures wherein caries originates. Nevertheless, sealers are sparingly used to date, as they cause a sensation of discomfort.  
         [0010]     A further, widespread caries remedy are alkaline substances (such as bicarbonates), that are able to buffer excessive acidity of the oral cavity.  
         [0011]     It will be appreciated that none of the aforementioned remedies counteracts ptyalin action, i.e. metabolisation of starch to highly cariogenic simple sugars. Starch residues, being sticky in nature, are nowadays deemed to be more dangerous than simple sugars that are soluble and easily eluted away from the oral cavity. 
     
    
     DESCRIPTION OF THE INVENTION  
       [0012]     The present invention relates to compositions containing salivar ptyalin inhibitors, in particular phaseolamin.  
         [0013]     Phaseolamin, extracted from common bean ( Phaseolus vulgaris ), is a thermolabile and gastrolabile protein having anti-ptyalin activity, that specifically inhibits conversion of starch to simple sugars. This inhibition makes starch residues harmless and stops from the beginning the metabolisation of sugars to acids, in particular lactic acid, which cause tooth demineralisation and caries.  
         [0014]     The compositions of the present invention can be in the solid form, for example mouth-soluble, slow-release tablets, candies or chewing gums; in the semi-solid form, such as gels, toothpastes, and the like; or in the liquid form, such as mouth-washes and the like.  
         [0015]     The compositions of the present invention can optionally comprise auxiliary substances, such as alkali (alkali carbonates or bicarbonates), inorganic fluorides, such as zinc fluoride, sodium fluoride, potassium fluoride, chlorhexidine or derivatives thereof or other bacteriostatic and bactericidal compounds, anti-inflammatory and soothing agents such as 18β-glycyrrhizinic acid,  Krameria triandra  extracts, green tea, etc.  
         [0016]     Particularly preferred are compositions containing, in addition to phaseolamin, one or more of alkali carbonates or bicarbonates, sodium monofluorophosphate, inorganic fluorides, chlorhexidine and derivatives thereof, 18β-glycyrrhizinic acid,  Krameria triandra  extract, green tea extract.  
         [0017]     The compositions of the invention can be prepared according to conventional techniques, and can contain excipients selected from thickening agents, such as base gum (in the case of chewing gums), hydroxypropyl cellulose, hydroxyethylcellulose, guar gum, gum arabic, cellulose gum; wetting agents; sweetening agents, in particular non cariogenic sweetening agents, such as xylitol, maltitol, acesulfame K, maltitol, aspartame; flavours; whitenings; abrasives, such as phosphate derivatives, preferably sodium monofluorophosphate, tricalcium phosphate, zinc orthophosphate, hydrate alumina, calcium carbonate, bentonite; desensitizing agents, such as potassium and strontium salts; zinc citrate; triclosan.  
         [0018]     The weight amount of phaseolamin in the compositions of the invention can vary within broad ranges, but is typically from about 0.01 to about 2%, preferably from about 0.1 to about 1%.  
         [0019]     The concentrations of the other ingredients are in principle similar to those of similar products for oral and dental hygiene.  
         [0020]     The following examples illustrate the invention in greater detail.  
       EXAMPLE 1 
       [0021]    
       
         
               
             
               
               
               
               
             
               
               
               
               
             
           
               
                   
               
               
                   
               
               
                 SLOW-RELEASE ANTICARIES COMPOSITION 1 
               
               
                 Type: 500 mg tablets 
               
               
                 Daily dosage: 1 tablet after each meal 
               
             
          
           
               
                   
                   
                 AMOUNT 
                   
               
               
                   
                 INGREDIENT 
                 mg 
                 % 
               
               
                   
                   
               
             
          
           
               
                   
                 Sorbitol 
                 447.790 
                 89.56 
               
               
                   
                 Flavour 
                 30.000 
                 6.00 
               
               
                   
                 Phaseolamin 
                 5.000 
                 1.00 
               
               
                   
                 Aspartame 
                 10.000 
                 2.00 
               
               
                   
                 Sodium Fluoride 
                 2.210 
                 0.44 
               
               
                   
                 Magnesium stearate 
                 5.000 
                 1.00 
               
               
                   
                 TOTAL 
                 500 
               
               
                   
                   
               
             
          
         
       
     
       EXAMPLE 2 
       [0022]    
       
         
               
             
               
               
               
               
             
               
               
               
               
             
           
               
                   
               
               
                   
               
               
                 SLOW-RELEASE ANTICARIES COMPOSITION 2 
               
               
                 Type: 500 mg tablets 
               
               
                 Daily dosage: 1 tablet after each meal 
               
             
          
           
               
                   
                   
                 AMOUNT 
                   
               
               
                   
                 INGREDIENT 
                 mg 
                 % 
               
               
                   
                   
               
             
          
           
               
                   
                 Saccharose 
                 455.000 
                 91.00 
               
               
                   
                 Flavour 
                 30.000 
                 6.00 
               
               
                   
                 Phaseolamin 
                 5.000 
                 1.00 
               
               
                   
                 18β-glycyrrhizinic acid 
                 5.000 
                 1.00 
               
               
                   
                 Magnesium stearate 
                 5.000 
                 1.00 
               
               
                   
                 TOTAL 
                 500 
               
               
                   
                   
               
             
          
         
       
     
       EXAMPLE 3 
       [0023]    
       
         
               
             
               
               
               
               
             
               
               
               
               
             
           
               
                   
               
               
                   
               
               
                 1.35 g ANTICARIES CHEWING GUM 1 
               
               
                 Daily dosage: 1 dose after each meal 
               
             
          
           
               
                   
                   
                 AMOUNT 
                   
               
               
                   
                 INGREDIENT 
                 mg 
                 % 
               
               
                   
                   
               
             
          
           
               
                   
                 Sorbitol 
                 600.000 
                 44.44 
               
               
                   
                 Isomalt 
                 300.000 
                 22.22 
               
               
                   
                 Xylitol 
                 200.000 
                 14.81 
               
               
                   
                 Maltitol syrup 
                 89.500 
                 6.63 
               
               
                   
                 Gum base 
                 70.000 
                 5.19 
               
               
                   
                 Aspartame 
                 12.000 
                 0.89 
               
               
                   
                 Acesulfame K 
                 12.000 
                 0.89 
               
               
                   
                 Flavour 
                 12.000 
                 0.89 
               
               
                   
                 Titanium dioxide E171 
                 12.000 
                 0.89 
               
               
                   
                 Gum arabic 
                 15.000 
                 1.11 
               
               
                   
                 18β-glycyrrhizinic acid 
                 10.000 
                 0.74 
               
               
                   
                 Sodium bicarbonate 
                 5.500 
                 0.41 
               
               
                   
                 Phaseolamin 
                 2.000 
                 0.15 
               
               
                   
                 Carnauba wax 
                 5.000 
                 0.37 
               
               
                   
                 E320 
                 5.000 
                 0.37 
               
               
                   
                 TOTAL 
                 1.350 
               
               
                   
                   
               
             
          
         
       
     
       EXAMPLE 4 
       [0024]    
       
         
               
             
               
               
               
               
             
               
               
               
               
             
           
               
                   
               
               
                   
               
               
                 1.35 g ANTICARIES CHEWING GUM 2 
               
               
                 Daily dosage: 1 dose after each meal 
               
             
          
           
               
                   
                   
                 AMOUNT 
                   
               
               
                   
                 INGREDIENT 
                 mg 
                 % 
               
               
                   
                   
               
             
          
           
               
                   
                 Sorbitol 
                 600.000 
                 44.44 
               
               
                   
                 Isomalt 
                 300.000 
                 22.22 
               
               
                   
                 Xylitol 
                 200.000 
                 14.81 
               
               
                   
                 Maltitol syrup 
                 98.395 
                 7.29 
               
               
                   
                 Gum base 
                 70.000 
                 5.19 
               
               
                   
                 Aspartame 
                 12.000 
                 0.89 
               
               
                   
                 Acesulfame K 
                 12.000 
                 0.89 
               
               
                   
                 Flavour 
                 12.000 
                 0.89 
               
               
                   
                 Titanium dioxide E171 
                 12.000 
                 0.89 
               
               
                   
                 Gum arabic 
                 15.000 
                 1.11 
               
               
                   
                 Sodium fluoride 
                 1.105 
                 0.08 
               
               
                   
                 Sodium bicarbonate 
                 5.500 
                 0.41 
               
               
                   
                 Phaseolamin 
                 2.000 
                 0.15 
               
               
                   
                 Carnauba wax 
                 5.000 
                 0.37 
               
               
                   
                 E320 
                 5.000 
                 0.37 
               
               
                   
                 TOTAL 
                 1.350 
               
               
                   
                   
               
             
          
         
       
     
       EXAMPLE 5 
       [0025]    
       
         
               
             
               
               
               
               
             
               
               
               
               
             
           
               
                   
               
               
                   
               
               
                 1.35 g ANTICARIES CHEWING GUM 2 
               
               
                 Daily dosage: 1 dose after each meal 
               
             
          
           
               
                   
                   
                 AMOUNT 
                   
               
               
                   
                 INGREDIENT 
                 mg 
                 % 
               
               
                   
                   
               
             
          
           
               
                   
                 Sorbitol 
                 600.000 
                 44.44 
               
               
                   
                 Isomalt 
                 300.000 
                 22.22 
               
               
                   
                 Xylitol 
                 200.000 
                 14.81 
               
               
                   
                 Maltitol syrup 
                 94.395 
                 6.99 
               
               
                   
                 Gum base 
                 70.000 
                 5.19 
               
               
                   
                 Aspartame 
                 12.000 
                 0.89 
               
               
                   
                 Acesulfame K 
                 12.000 
                 0.89 
               
               
                   
                 Flavour 
                 12.000 
                 0.89 
               
               
                   
                 Titanium dioxide E171 
                 12.000 
                 0.89 
               
               
                   
                 Gum arabic 
                 15.000 
                 1.11 
               
               
                   
                 Sodium fluoride 
                 1.105 
                 0.08 
               
               
                   
                 Sodium bicarbonate 
                 5.500 
                 0.41 
               
               
                   
                 
                   Krameria triandra 
                 
                 4.000 
                 0.30 
               
               
                   
                 Phaseolamin 
                 2.000 
                 0.15 
               
               
                   
                 Carnauba wax 
                 5.000 
                 0.37 
               
               
                   
                 E320 
                 5.000 
                 0.37 
               
               
                   
                 TOTAL 
                 1.350 
               
               
                   
                   
               
             
          
         
       
     
       EXAMPLE 6 
       [0026]    
       
         
               
             
               
               
               
               
             
               
               
               
               
             
           
               
                   
               
               
                   
               
               
                 ANTICARIES TOOTHPASTE 1 
               
               
                 750 ml TUBE 
               
             
          
           
               
                   
                 INGREDIENT 
                 AMOUNT g 
                 % 
               
               
                   
                   
               
             
          
           
               
                   
                 Calcium carbonate 
                 300.000 
                 40.00 
               
               
                   
                 Water 
                 270.000 
                 36.00 
               
               
                   
                 Sorbitol 
                 89.250 
                 11.90 
               
               
                   
                 Hydrated silica 
                 20.000 
                 2.67 
               
               
                   
                 Sodium Lauryl Sulfate 
                 20.000 
                 2.67 
               
               
                   
                 Sodium 
                 10.000 
                 1.33 
               
               
                   
                 Monofluorophosphate 
               
               
                   
                 Flavour 
                 8.000 
                 1.07 
               
               
                   
                 Cellulose Gum 
                 7.000 
                 0.93 
               
               
                   
                 Trisodium phoshate 
                 5.000 
                 0.67 
               
               
                   
                 Monosodium Phoshate 
                 5.000 
                 0.67 
               
               
                   
                 Sodium Saccharin 
                 5.000 
                 0.67 
               
               
                   
                 Phaseolamin 
                 3.750 
                 0.50 
               
               
                   
                 Chlorhexidine 
                 2.000 
                 0.27 
               
               
                   
                 CI74260 
                 5.000 
                 0.67 
               
               
                   
                 TOTAL 
                 750 
               
               
                   
                   
               
             
          
         
       
     
       EXAMPLE 7 
       [0027]    
       
         
               
             
               
               
               
               
             
               
               
               
               
             
           
               
                   
               
               
                   
               
               
                 ANTICARIES TOOTHPASTE 2 
               
               
                 750 ml TUBE 
               
             
          
           
               
                   
                 INGREDIENT 
                 AMOUNT g 
                 % 
               
               
                   
                   
               
             
          
           
               
                   
                 Calcium carbonate 
                 300.000 
                 40.00 
               
               
                   
                 Water 
                 270.000 
                 36.00 
               
               
                   
                 Sorbitol 
                 85.250 
                 11.37 
               
               
                   
                 Hydrated silica 
                 20.000 
                 2.67 
               
               
                   
                 Sodium Lauryl Sulfate 
                 20.000 
                 2.67 
               
               
                   
                 Sodium 
                 10.000 
                 1.33 
               
               
                   
                 Monofluorophosphate 
               
               
                   
                 Flavour 
                 8.000 
                 1.07 
               
               
                   
                 Cellulose Gum 
                 7.000 
                 0.93 
               
               
                   
                 18β-glycyrrhizinic acid 
                 6.000 
                 0.80 
               
               
                   
                 Trisodium phoshate 
                 5.000 
                 0.67 
               
               
                   
                 Monosodium Phoshate 
                 5.000 
                 0.67 
               
               
                   
                 Sodium Saccharin 
                 5.000 
                 0.67 
               
               
                   
                 Phaseolamin 
                 3.750 
                 0.50 
               
               
                   
                 CI74260 
                 5.000 
                 0.67 
               
               
                   
                 TOTAL 
                 750 
               
               
                   
                   
               
             
          
         
       
     
       EXAMPLE 8 
       [0028]    
       
         
               
             
               
               
               
               
             
               
               
               
               
             
           
               
                   
               
               
                   
               
               
                 ANTICARIES TOOTHPASTE 1 
               
               
                 750 ml TUBE 
               
             
          
           
               
                   
                 INGREDIENT 
                 AMOUNT g 
                 % 
               
               
                   
                   
               
             
          
           
               
                   
                 Calcium carbonate 
                 300.000 
                 40.00 
               
               
                   
                 Water 
                 270.000 
                 36.00 
               
               
                   
                 Sorbitol 
                 88.250 
                 11.77 
               
               
                   
                 Hydrated silica 
                 20.000 
                 2.67 
               
               
                   
                 Sodium Lauryl Sulfate 
                 20.000 
                 2.67 
               
               
                   
                 Sodium 
                 10.000 
                 1.33 
               
               
                   
                 Monofluorophosphate 
               
               
                   
                 Flavour 
                 8.000 
                 1.07 
               
               
                   
                 Cellulose Gum 
                 7.000 
                 0.93 
               
               
                   
                 Trisodium phoshate 
                 5.000 
                 0.67 
               
               
                   
                 Monosodium Phoshate 
                 5.000 
                 0.67 
               
               
                   
                 Sodium Saccharin 
                 5.000 
                 0.67 
               
               
                   
                 Phaseolamin 
                 3.750 
                 0.50 
               
               
                   
                 
                   Krameria triandra 
                 
                 3.000 
                 0.40 
               
               
                   
                 CI74260 
                 5.000 
                 0.67 
               
               
                   
                 TOTAL 
                 750