Prolonged release bioadhesive therapeutic systems

Abstract

The present invention concerns a prolonged release bioadhesive mucosal therapeutic system containing at least one active principle, with an active principle dissolution test of more than 70% over 8 hours and to a method for its preparation. Said bioadhesive therapeutic system comprises quantities of natural proteins representing at least 50% by weight of active principle and at least 20% by weight of said tablet, between 10% and 20% of a hydrophilic polymer, and compression excipients, and comprising between 4% and 10% of an alkali metal alkylsulphate to reinforce the local availability of active principle and between 0.1% and 1% of a monohydrate sugar.

1 . A prolonged release bioadhesive therapeutic system containing at least one active principle, having an active principle dissolution percentage of more than 70% over 8 hours, comprising quantities of natural proteins representing at least 50% by weight of active principle and at least 20% by weight of said bioadhesive therapeutic system, between 10% and 20% of a hydrophilic polymer, compression excipients, and comprising between 3.5% and 10% of an alkali metal alkylsulphate. 
     
     
         2 . The bioadhesive therapeutic system according to  claim 1 , wherein said bioadhesive therapeutic system is a mucoadhesive tablet. 
     
     
         3 . The bioadhesive therapeutic system according to  claim 2 , wherein the alkali metal alkylsulphate is sodium laurylsulphate or diethylsulphosuccinate. 
     
     
         4 . The bioadhesive therapeutic system according to  claim 3 , in the form of a tablet in which the alkylsulphate is sodium laurylsulphate in a concentration of 3.5% to 10%, of the total weight of the compounds in the tablet. 
     
     
         5 . The bioadhesive therapeutic system according to  claim 1 , wherein the compression excipients contain corn starch. 
     
     
         6 . The bioadhesive therapeutic system according to  claim 1 , in which one of the active principle is an antifungal from the broad spectrum azole family. 
     
     
         7 . The bioadhesive therapeutic system according to  claim 6 , in the form of a tablet in which the azole is miconazole present in a dose of 10 to 150 mg per tablet. 
     
     
         8 . The bioadhesive therapeutic system according to  claim 7 , in which the active principle is a broad spectrum azole, in association with a further active principle selected from:
 a polyene type antifungal with a different spectrum;   an analgesic;   a salivation agent; an antiseptic;   a salivary substitute;   an anti-inflammatory (corticoids);   an antibiotic;   thalidomide;   or a mixture thereof.   
     
     
         9 . The bioadhesive therapeutic system according to  claim 8 , in which the second active principle is a polyene in a dose of 10 to 100 mg per tablet. 
     
     
         10 . The bioadhesive therapeutic system according to  claim 8 , further comprising 0.1% to 10% by weight of anaesthetic and/or 0.1% to 10% by weight of salivation agent. 
     
     
         11 . The bioadhesive therapeutic agent according to  claim 1 , in which the active principle is an antiseptic. 
     
     
         12 . The bioadhesive therapeutic system according to  claim 11 , in which the antiseptic is sodium laurylsulphate in a minimum concentration of 3.5% by weight. 
     
     
         13 . The bioadhesive therapeutic system according to  claim 1 , in which the active principle is an antiviral that is active for HSV viruses (herpes) VZV (varicella zoster virus), Epstein-Barr virus (infections mononucleosis, hairy leukoplakia), cytomegalovirus. 
     
     
         14 . The bioadhesive therapeutic system according to  claim 13 , in which the antiviral is present either in an amount of 20 to 100 mg or 10 to 2000 mg. 
     
     
         15 . The bioadhesive therapeutic system according to  claim 1 , in which the active principle is an antiviral active against HIV virus (human immunodeficiency virus) 
     
     
         16 . The bioadhesive therapeutic system according to  claim 15 , in which the active principle is present in an amount of 10 to 2000_mg_per bioadhesive therapeutic system. 
     
     
         17 . The bioadhesive therapeutic system according to  claim 1 , in which the active principle is an insoluble analgesic from the opioid family. 
     
     
         18 . The bioadhesive therapeutic system according to  claim 17 , in which the insoluble anagesic from the opioid family is present in an amount of 50 to 1600 micrograms per bioadhesive therapeutic system. 
     
     
         19 . A tablet according to  claim 4 , in which the sodium lauryisuiphate is in a concentration of 4% to 6% of the total weight of the compounds in the tablet. 
     
     
         20 . A bioadhesive therapeutic system according to  claim 6 , in which the antifungal from the broad spectrum azole family is selected from the group consisting of miconazole, clotrimazole, ketoconazole, fluconazole, itraconazole, isoconazole, econazole, saperconazole, genaconazole, terconazole, butoconazole, tioconazole, oxiconazole, bifonazole, fenticonazole, ornoconazole, sertaconazole and sulconazole. 
     
     
         21 . The bioadhesive therapeutic system according to  claim 7 , in which the miconazole is present in a dose of 25 to 75 mg per tablet. 
     
     
         22 . The bioadhesive therapeutic system according to  claim 7 , in which the miconazole is present in a dose of 50 mg per table. 
     
     
         23 . The bioadhesive therapeutic system according to  claim 9 , in which the polyene is in a dose of 20 to 90 mg. 
     
     
         24 . The bioadhesive therapeutic system according to  claim 13 , in which the antiviral is acyclovir, valaciclovir, zidovudine or ganciclovir. 
     
     
         25 . The bioadhesive therapeutic according to  claim 24 , in which the aciclovir and valaciclovir are present in an amount of 50 mg, and the zidovudine and ganciclovir are present in an amount of 500 to 1500 mg. 
     
     
         26 . The bioadhesive therapeutic system according to  claim 15 , in which the antiviral is zidovudine (AZT). 
     
     
         27 . The bioadhesive therapeutic system according to  claim 16 , which is a vaginal system. 
     
     
         28 . The bioadhesive therapeutic system according to  claim 16 , in which the active principle is present in an amount of 500 to 1500 mg. 
     
     
         29 . The bioadhesive therapeutic system according to  claim 17 , in which the insoluble analgesic is fentanyl. 
     
     
         30 . The bioadhesive therapeutic system according to  claim 29 , which the fentanyl is an insoluble base. 
     
     
         31 . The bioadhesive therapeutic system according to  claim 29 , in which the fentanyl is present in an amount of 200 to 1200 micrograms.