Delivery of drugs to mucosal surfaces

Abstract

Liquid pharmaceutical compositions for administration to a mucosal surface, including a therapeutic agent and a pectin with a low degree of esterification are described. Such compositions gel, or can be adapted to gel, at the site of application in the absence of an extraneous source of divalent metal ions.

1 . A liquid pharmaceutical composition for administration to the mucosa of the nasal cavity comprising: 
 a therapeutic agent,    a pectin that has a degree of esterification that is less than 50%, and    an aqueous carrier, wherein the composition gels or is adapted to gel at a site of application on the mucosal surface in the absence of an extraneous source of divalent metal ions.    
   
   
       2 . The composition of  claim 1 , wherein the therapeutic agent acts locally at the mucosa of the nasal cavity.  
   
   
       3 . The composition of  claim 2 , wherein the therapeutic agent is selected from the group consisting of a steroid, an antiviral agent, a decongestant, an anti-allergic agent, and an antihistamine.  
   
   
       4 . The composition of  claim 2 , wherein the therapeutic agent is selected from the group consisting of an antifungal agent and an anti-bacterial agent.  
   
   
       5 . The composition of  claim 2 , wherein the therapeutic agent is a gene.  
   
   
       6 . The composition of  claim 2 , wherein the therapeutic agent is selected from the group consisting of a vaccine, an antibody, and a prophylactic agent against HIV.  
   
   
       7 . The composition of  claim 2 , wherein the therapeutic agent is selected from fluticasone, pirovadir ICAM- 1, acyclovir, bromovinyldeoxyuridine, α-interferon, β-interferon, γ-interferon, zidovudine, oxymetazoline, sodium cromoglycate, budesonide and diphenhydramine hydrochloride.  
   
   
       8 . The composition of  claim 2 , wherein the therapeutic agent is selected from the group consisting of amphotericin, nystatin, a vaccine against influenza, a vaccine against pertussis, a vaccine against measles, and a vaccine against diphtheria.  
   
   
       9 . The composition of  claim 2 , wherein the therapeutic agent is selected from the group consisting of a deoxyribonucleic acid vaccine and an antibody against respiratory syncytial virus.  
   
   
       10 . The composition of  claim 2 , wherein the therapeutic agent is fexofenadine.  
   
   
       11 . The composition of  claim 1 , wherein the therapeutic agent acts systemically.  
   
   
       12 . The composition of  claim 11 , wherein the therapeutic agent is selected from the group consisting of nicotine, hyoscine hydrobromide, lignocaine, naratriptan, a pheromone, and propranolol.  
   
   
       13 . The composition of  claim 11 , wherein the therapeutic agent is apomorphine.  
   
   
       14 . The composition of  claim 11 , wherein the therapeutic agent is fentanyl.  
   
   
       15 . The composition of  claim 1 , wherein the pectin has a degree of esterification that is less than 35%.  
   
   
       16 . The composition of  claim 1 , wherein the composition is in a form selected from the group consisting of a free flowing system and a spray.  
   
   
       17 . The composition of  claim 1 , wherein the composition has a pH of 2 to 9.  
   
   
       18 . The composition of  claim 1 , wherein the pectin is present in a concentration of 1 g/L to 100 g/L.  
   
   
       19 . The composition of  claim 1 , wherein the pectin is present in a concentration of 1 g/L to 50 g/L.  
   
   
       20 . A pharmaceutical gel composition prepared by applying a liquid composition according to  claim 1  to the mucosa of the nasal cavity of a mammal in the absence of extraneous divalent metal ions.  
   
   
       21 . The pharmaceutical gel composition of  claim 20 , wherein the pectin has a degree of esterification of less than 35%.  
   
   
       22 . A kit comprising a composition adapted for administration to the mucosa of the nasal cavity, the composition comprising a therapeutic agent, a pectin that has a degree of esterification of less than 50%, and an aqueous carrier which gels or is adapted to gel at the mucosa of the nasal cavity, but the kit does not include a solution of divalent metal ions.  
   
   
       23 . The kit of  claim 22 , wherein the therapeutic agent that acts locally at the mucosa of the nasal cavity is selected from the group consisting of a steroid, an anti-viral agent, a decongestant, an anti-allergic agent, an antihistamine, an anti-fungal agent, an antibacterial agent and a gene.  
   
   
       24 . The kit of  claim 22 , wherein the therapeutic agent that acts locally at the mucosa of the nasal cavity is selected from the group consisting of a vaccine, an antibody, a prophylactic agent against HIV, fluticasone, ICAM-1, pirovadir, acyclovir, bromovinyldeoxyuridine, α-interferon, β-interferon, γ-interferon, zidovudine, oxymetazoline, sodium cromoglycate, budesonide, and diphenhydramine hydrochloride.  
   
   
       25 . The kit of  claim 22 , wherein the therapeutic agent that acts locally at the mucosa of the nasal cavity is selected from the group consisting of amphotericin, nystatic, a vaccine against influenza, a vaccine against pertussis, a vaccine against measles, and a vaccine against diphtheria, a deoxyribonucleic acid vaccine, and an antibody against respiratory synctial virus.  
   
   
       26 . The kit of  claim 22 , wherein the therapeutic agent that acts locally at the mucosa of the nasal cavity is fexofenadine.  
   
   
       27 . The kit of  claim 22 , wherein the pectin has a degree of esterification that is less than 35%.  
   
   
       28 . The kit of  claim 22 , wherein the composition is in a form selected from the group consisting of a free flowing system and a spray.  
   
   
       29 . The kit of  claim 22 , wherein the composition has a pH of 2 to 9.  
   
   
       30 . The kit of  claim 22 , wherein the pectin is present in the composition in a concentration of 1 g/L to 100 g/L.  
   
   
       31 . The kit of  claim 22 , wherein the pectin is present in the composition in a concentration of 1 g/L to 50 g/L.  
   
   
       32 . The kit of  claim 22 , wherein the therapeutic agent that acts systemically is selected from the group consisting of nicotine, hyoscine hydrobromide, lignocaine, naratriptan, a pheromone, and propranolol.  
   
   
       33 . The kit of  claim 22 , wherein the therapeutic agent that acts systemically is apomorphine.  
   
   
       34 . The kit of  claim 22 , wherein the therapeutic agent that acts systemically is fentanyl.