Bioadhesive Composition With Programmed Release

Abstract

The invention relates to novel viscous liquid compositions for producing pasty forms having a prolonged action and/or release for local applications. These compositions are characterized in that the long-lasting action and/or the prolonged release of the active substance is obtained by the in-situ formation of a matrix film having an increased bioadhesive power and being more or less viscous and biodegradable. The invention also relates to a viscous liquid composition with an increased bioadhesive power for a local application in pasty form with a prolonged release of an active substance, whereby being characterized in that it contains at least one matrix agent, a medium for hydrating the matrix agent, and at least one active substance.

1 . A viscous liquid composition having reinforced bio-adhesive capacity, for a local application in pasty form with prolonged release of an active ingredient, characterized in that it includes:
 (i) a matrix agent allowing the in situ formation of a matrix film with reinforced bio-adhesive capacity obtained by a reaction of complexation of the matrix agent with one of the components of local secretions or of the mucous membrane,   (ii) a hydration medium for the matrix agent and   (iii) an active ingredient.   
     
     
         2 . A viscous liquid composition according to  claim 1 , characterized in that the matrix agent belongs to the family of polysaccharides. 
     
     
         3 . A viscous liquid composition according to  claim 2 , characterized in that polysaccharide belongs to the family of the carrageenans. 
     
     
         4 . A viscous liquid composition according to  claim 3 , characterized in that the carrageenan is selected among the lambda- and the iota-carrageenans 
     
     
         5 . A viscous liquid composition according to  claim 3 , characterized in that the carrageenan is has a concentration ranging between 0.5% and 30% in mass in relation to the total mass of the composition. 
     
     
         6 . A viscous liquid composition according to  claim 1 , characterized in that the hydration medium of the matrix agent is an aqueous solution or hydro-alcoholic. 
     
     
         7 . A viscous liquid composition according to  claim 6 , characterized in that the hydro-alcoholic phase includes ethanol or isopropyl alcohol. 
     
     
         8 . A viscous liquid composition according to  claim 6 , characterized in that the proportion in alcoholic phase lies between 10% and 90% in mass in relation to the volume total of the hydrating phase. 
     
     
         9 . A viscous liquid composition according to  claim 1 , characterized in that it furthermore includes alkaline or alkaline-earth ions. 
     
     
         10 . A viscous liquid composition according to  claim 9 , characterized in that the proportion of alkaline or alkaline-earth ions varies from 0 to 50% in mass in relation to the total mass of the composition. 
     
     
         11 . A viscous liquid composition according to  claim 9 , characterized in that the alkaline or alkaline-earth ions are introduced in the form of hydroxide or a salt of hydrochloric, sulphuric, nitric, phosphoric, citric acid and/or a derivative. 
     
     
         12 . A viscous liquid composition according to  claim 12 , characterized in that the aqueous phase of the hydration medium is a buffer solution. 
     
     
         13 . A viscous liquid composition according to  claim 12 , characterized in that the value of the pH of the buffer solution varies from 2 to 12. 
     
     
         14 . A viscous liquid composition according to  claim 12 , characterized in that the buffer solution is constituted by the couples hydrochloric acid/sodium chloride, hydrochloric acid/potassium phthalate, hydrochloric acid/glycol, citric acid/citrates, citric acid/sodium hydroxide, lactic acid/lactate, monosodium phosphate/disodium phosphate, monopotassium phosphate/dipotassium phosphate, bicarbonate/carbonate, acid/potassium diphthalate, or boric acid/sodium borate. 
     
     
         15 . A viscous liquid composition according to  claim 1 , characterized in that the active ingredient is solubilized in the hydrating phase or in an organic solvent. 
     
     
         16 . A viscous liquid composition according to  claim 15 , characterized in that the organic solvent is selected among vegetable oils, mineral oils, natural oils, synthetic oils, conventional lipophilic solvents, hydrophilics and non-toxic hydro-lipophilics. 
     
     
         17 . A viscous liquid composition according to  claim 1 , characterized in that it furthermore includes a surface-active agent 
     
     
         18 . A viscous liquid composition according to  claim 17 , characterized in that the surface-active agent belongs to the class of ionic, nonionic and amphoteric surface-active agents. 
     
     
         19 . A viscous liquid composition according to  claim 17 , characterized in that the concentration of surface-active agent lies between 0 and 50% in mass in relation to the total mass of the excipients. 
     
     
         20 . A viscous liquid composition according to  claim 1 , characterized in that the active ingredient in the solid state is dispersed in the form of powder of a granulometry ranging between 1 μm and 1000 μm. 
     
     
         21 . A viscous liquid composition according to  claim 20 , characterized in that the granulometry of the active ingredient lies between 1 μm and 250 μm. 
     
     
         22 . A viscous liquid composition according to  claim 1 , characterized in that it furthermore includes starch of rice, of potato, of corn, of manioc, and their derivatives. 
     
     
         23 . A viscous liquid composition according to  claim 22 , characterized in that modified starch or the starch concentration lies between 0 and 50% in mass in relation to the total mass of the composition. 
     
     
         24 . A viscous liquid composition according to  claim 1 , characterized in that it includes a conservation moistening, coloring, flavoring and/or sweetening agent. 
     
     
         25 . A viscous liquid composition according to  claim 24  characterized in that the concentration in preservatives lies between 0 and 10%. 
     
     
         26 . A viscous liquid composition according to  claim 24  characterized in that the concentration in moistening agents lies between 1 and 30%. 
     
     
         27 . A viscous liquid composition according to  claim 24 , characterized in that the concentration in dyes lies between 0 and 5%. 
     
     
         28 . A viscous liquid composition according to  claim 24 , characterized in that the concentration in sweetening substances lies between 0 and 30%. 
     
     
         29 . A viscous liquid composition according to  claim 24 , characterized in that the sweetening substances are natural or synthetic chosen among saccharose, aspartame, acesulfam, sodium cyclamate or sodium saccharinate. 
     
     
         30 . A viscous liquid composition according to  claim 1  characterized in that it presents a viscosity ranging between 100 mPa and 500,000 mPa. 
     
     
         31 . A viscous liquid composition according to  claim 1  characterized in that the release time of the active ingredient lies between 2 and 12 hours for the oral, nasal, and ocular routes. 
     
     
         32 . A viscous liquid composition according to  claim 1  characterized in that the release time of the active ingredient is greater than 12 hours for the vaginal route. 
     
     
         33 . A viscous liquid composition according to  claim 1 , characterized in that the active ingredient belongs to a therapeutic class selected among: analgesics, anti-inflammatories, antispasmodics, cytotoxics, antibiotics, antifungals, disinfectants, anti-parasitics, hormones, antivirals, anti-migraine agents, antiallergics, respiratory agents, analeptics, spermicides, anti-hemorrhoidal agents, vasoconstrictors, vasodilators, antipruritics, uterorelaxants, antiglaucoma agents, mydriatics and antiasthmatics. 
     
     
         34 . A viscous liquid composition according to  claim 1  furthermore including alkaline or alkaline-earth ions of sodium or potassium.