Mucosal Bioadhesive SLow Release Carrier for Delivering Active Principles

Abstract

A mucosal bioadhesive slow release carrier comprising an active principle and devoid of starch, lactose, which can release the active principal for a duration of longer than 20 hours. This bioadhesive carrier contains a diluent, an alkali metal alkylsulfate, a binding agent, at least one bioadhesive polymer and at least one sustained release polymer, as well as a method for its preparation.

1 - 33 . (canceled) 
   
   
       34 . A mucosal bioadhesive slow release carrier comprising a wetting agent comprising at least one active principle, 1 to 75% by weight of a diluent and 1 to 10% by weight of an alkali metal alkylsulfate and further comprising 0.5 to 5% by weight of a binding agent and 5 to 80% by weight of at least one bioadhesive polymer selected from the group of natural polymers wherein said natural polymers are polysaccharides or natural proteins from animal origin such as milk protein or protein from vegetable origin such as pea protein or synthetic polymers and mixtures thereof and 5% to 80% by weight of at least one polymer that provides a sustained release of the active principle. 
   
   
       35 . The mucosal bioadhesive slow release carrier according to  claim 34 , wherein said at least one active principle is selected from: an antiviral, an analgesic, an anaesthetic, an antalgic, an anti-inflammatory, an antibiotic, an antiseptic, an antiemetic and mixtures thereof. 
   
   
       36 . The mucosal bioadhesive slow release carrier according to  claim 34 , wherein the alkali metal alkylsulfate is sodium lauryl sulfate. 
   
   
       37 . The mucosal bioadhesive slow release carrier according to  claim 34  wherein the binding agent is polyvinylpyrrolidone. 
   
   
       38 . The mucosal bioadhesive slow release carrier according to  claim 34 , wherein the at least one adhesive polymer comprises milk natural proteins in a concentration from 10 to 40% by weight. 
   
   
       39 . The mucosal bioadhesive slow release carrier according to  claim 34 , wherein the at least one polymer that provides a sustained release of the at least one active principle is hydrophilic and preferably a cellulose polymer. 
   
   
       40 . The mucosal bioadhesive slow release carrier according to  claim 39 , wherein the cellulose polymer is hypromellose. 
   
   
       41 . The mucosal bioadhesive slow release carrier according to  claim 34 , wherein said at least one active principle is an antiviral selected from acyclovir, valacyclovir, zidovudine, ganciclovir, penciclovir, famciclovir, foscarnet, ribavirin, lamiduvine, amantadine, IFNα, cidofovir or rimantadine. 
   
   
       42 . The mucosal bioadhesive slow release carrier according to  claim 41 , wherein said antiviral is acyclovir. 
   
   
       43 . The mucosal bioadhesive slow release carrier according to  claim 42 , wherein said acyclovir is present in an amount from 10 to 500 mg in said carrier. 
   
   
       44 . The mucosal bioadhesive slow release carrier according to  claim 42 , wherein said acyclovir is present in an amount from 50 to 100 mg in said carrier. 
   
   
       45 . The mucosal bioadhesive slow release carrier according to  claim 34 , wherein said at least one active principle is fentanyl or fentanyl citrate or sulfentanyl and is present in an amount of 50 to 1600 μg in said carrier. 
   
   
       46 . The mucosal bioadhesive slow release carrier according to  claim 45 , wherein said fentanyl or fentanyl citrate or sulfentanyl and is present in an amount of from 200 to 1200 μg in said carrier. 
   
   
       47 . The mucosal bioadhesive slow release carrier according to  claim 34 , wherein said at least one active principle is an anti-inflammatory. 
   
   
       48 . The mucosal bioadhesive slow release carrier according to  claim 47 , wherein said anti-inflammatory is a corticoid. 
   
   
       49 . The mucosal bioadhesive slow release carrier according to  claim 34 , wherein said carrier is devoid of lactose and of corn starch. 
   
   
       50 . The mucosal bioadhesive slow release carrier according to  claim 34 , wherein said at least one active principle is an antiviral that is active for herpes simplex viruses (HSV), varicella zoster virus (VZV), Epstein-Barr 
     virus, human herpes virus 8, avian influenza, mumps, HIV, respiratory syncitial virus, influenza, parainfluenza and cytomegalovirus. 
   
   
       51 . The mucosal bioadhesive slow release carrier according to  claim 34 , wherein the at least one active principle is associated with at least two further active principles selected from: an antiviral, an antifungal, an analgesic, an anaesthetic, an antalgic, an antiemetic, a salivation agent, an antiseptic, an anti-inflammatory, an antibiotic and mixtures thereof. 
   
   
       52 . The mucosal bioadhesive slow release carrier according to  claim 35 , wherein the antiseptic is sodium laurylsulfate in a minimum concentration of 2 to 10% by weight. 
   
   
       53 . A method for preparing a mucosal bioadhesive slow release carrier comprising: a) granulating a mixture of at least one active principle with an alkali metal alkylsulfate, a binding agent and a diluent; b) blending said granulated mixture with at least one bioadhesive polymer, at least one polymer that provides a sustained release and at least one compression agent; and c) compressing the blended mixture obtained in b). 
   
   
       54 . The method according to  claim 53 , wherein, said mixture is first granulated and dried prior to calibration. 
   
   
       55 . The method according to  claim 53 , wherein said at least one active principle is a hydrosoluble active principle and wherein said at least one diluent is an insoluble diluent. 
   
   
       56 . The method according to  claim 53 , wherein said at least one active principle is an insoluble active principle and wherein said at least one diluent is a hydrosoluble diluent. 
   
   
       57 . The method according to  claim 53 , wherein the binding agent is polyvinylpyrrolidone. 
   
   
       58 . The method according to  claim 53 , wherein the at least one bioadhesive polymer comprises natural proteins selected from the group of natural milk proteins, carbomer, alginate, chitosan, xanthum gum, hydroxypropyl cellulose, polyvinylalcohol, carboxymethyl cellulose, hydroxypropyl methyl cellulose, hydroxyethyl cellulose, sodium-hyaluronate, acrylic polymers and mixtures thereof. 
   
   
       59 . The method according to  claim 53 , wherein the at least one sustained release polymer is a cellulose polymer or a derivative of a cellulose polymer. 
   
   
       60 . The method according to  claim 59 , wherein said cellulose polymer is hypromellose. 
   
   
       61 . The method according to  claim 53 , wherein said at least one active principle is selected from: an antiviral, an antifungal, an analgesic, an anaesthetic, an antalgic, an antiemetic, a salivation agent, an antiseptic, an antiinflammatory, an antibiotic, and mixtures thereof. 
   
   
       62 . The method according to  claim 61 , wherein the at least one active principle is associated with a further active principle selected from: an antiviral; an antifungal, an analgesic, an anaesthetic, an antalgic, an antiemetic, a salivation agent, an antiseptic, an anti-inflammatory, an antibiotic and mixtures thereof. 
   
   
       63 . Use of the mucosal bioadhesive slow release carrier according to  claim 34  for the manufacture of a medicament to treat mucosal diseases. 
   
   
       64 . Use according to  claim 63 , wherein the mucosal diseases are buccal diseases. 
   
   
       65 . Use according to  claim 64 , wherein the buccal diseases are selected from: herpes simplex complex 1 (HSV-1), genital herpes (HSV-2), oral mucositis, oral Candidiasis, oral hairy leukoplakia, oral ulcers, salivary gland disturbance, altered oral flora (decreased bacterial flora), taste dysfunction, periodontitis, xerostomia, gastrointestinal mucositis causing secondary changes in oral status including inflammation, hygiene and dietary intact and oral pain. 
   
   
       66 . Use of the mucosal bioadhesive slow release carrier according to  claim 34  for the manufacture of a medicament to treat herpes simplex complex 1 (HSV-1), genital herpes (HSV-2) Epstein-Barr virus, human papilloma virus, cytomegalovirus, variacella-Zoster virus, Kaposi's sarcoma due to human herpes V 8 and genital warts due to human papilloma virus.