Packaged stable enema solution or suspension containing 5-aminosalicyclic acid

Abstract

A packaged enema solution or suspension consisting essentially of an effective amount of 5-ASA or a pharmaceutically acceptable salt or ester thereof, a chelating agent, in antioxidant and a buffer, the solution or suspension having a pH value of from 4 to 7 and being contained in a plastic bottle under an inert gas, the plastic bottle being packaged in a diffusion-tight light-impervious package in the same inert gas as is present in the bottle.

What is claimed is: 
     
       1. A packaged enema solution or suspension consisting essentially of an effective amount of 5-ASA or a pharmaceutically acceptable salt or ester thereof, a chelating agent, an antioxidant and a buffer, said solution or suspension having a pH value of about 4.8 and being contained in a plastic bottle under an inert gas, said plastic bottle being packaged in a diffusion-tight light-impervious package in the same inert gas as is present in the bottle. 
     
     
       2. A packaged enema solution or suspension according to claim 1, wherein the chelating agent comprises EDTA, the antioxidant comprises sodium pyrosulfite and the buffer comprises citric acid and sodium hydroxide. .[.3. A packaged enema solution or suspension according to claim 1, 
     
     
        wherein the buffer is sodium bicarbonate and hydrochloric acid..]. 4. An enema solution or suspension according to claim 1, wherein the .[.5-aminosalicyclic.]. .Iadd.5-aminosalicylic .Iaddend.acid is sufficiently pure to avoid autooxidation, having no additional HPLC 
     
     
        fluospectrophotometric and spectrophotometric peaks. 5. A packaged enema solution or suspension according to claim 1, wherein the inert gas is 
     
     
        argon, nitrogen or carbon dioxide. 6. A packaged enema solution or suspension according to claim 1 consisting essentially of substantially pure .[.5-aminosalicyclic.]. .Iadd.5-aminosalicylic .Iaddend.acid or a pharmaceutically acceptable salt or ester thereof, ethylenediaminetetraacetic acid, sodium pyrosulfite, citric acid, sodium 
     
     
        hydroxide and purified water. 7. A packaged enema solution or suspension 
     
     
        according to claim 1, wherein the plastic bottle is polyethylene. 8. A packaged enema solution or suspension according to claim 7, wherein a polyethylene granulate used for producing the polyethylene bottle is deoxidized by alternately evacuating the granulate and flooding the 
     
     
        granulate with nitrogen gas. 9. A package enema solution or suspension according to claim 8, wherein the deoxidized granulate is extruded, formed into a bottle by means of an inert gas, and the bottle is filled with said 
     
     
        enema solution. 10. A package enema solution or suspension according to claim 9, the filled bottle is conveyed directly to a packing chamber wherein the bottle is packed into an aroma-tight bag under an inert gas, 
     
     
        said bag being sealed by welding before being contacted with air. 11. A packaged enema solution or suspension according to claim 10, wherein the 
     
     
        aroma-tight bag is a plastic aluminum laminate. 12. A packaged enema solution or suspension according to claim 11, containing per 100 ml of solution about 0.2 to 4.0 g .[.5-aminosalicyclic.]. .Iadd.5-aminosalicylic .Iaddend.acid, about 50 mg to 200 mg of sodium pyrosulfite, about 0.5 to 1.5 g citric acid, about 0.5 to 2 g sodium hydroxide, about 5 to 30 mg 
     
     
        sodium EDTA, and purified water. 13. A packaged enema solution or suspension according to claim 12, containing per 100 ml of solution about 1 g of .[.5-aminosalicyclic.]. .Iadd.5-aminosalicylic .Iaddend.acid, about 200 mg of sodium pyrosulfite, about 1 g citric acid, about 20 mg sodium EDTA, and sufficient sodium hydroxide and purified water to maintain said 
     
     
        pH of 4.8. .Iadd.14.  A packaged enema solution or suspension consisting essentially of an effective amount of 5-ASA or a pharmaceutically acceptable salt or ester thereof, a chelating agent, an antioxidant and a buffer, said solution or suspension having a pH value of from 4 to 5 and being contained in a plastic bottle under an inert gas, said plastic bottle being packaged in a diffusion-tight light-impervious package in the same inert gas as is present in the bottle. .Iaddend. .Iadd.15. A packaged enema solution or suspension according to claim 14, wherein the antioxidant is sodium or potassium pyrosulfite. .Iaddend. .Iadd.16. A packaged enema solution or suspension according to claim 15, wherein the pyrosulfite is potassium pyrosulfite. .Iaddend. .Iadd.17. A packaged enema solution or suspension according to claim 16, containing per 100 ml of solution or suspension about 50 mg to 200 mg of potassium pyrosulfite. .Iaddend. .Iadd.18. A packaged enema solution or suspension according to claim 17, wherein the chelating agent is ethylene diaminetetraacetic acid or one of its alkali metal salts. .Iaddend. .Iadd.19. A packaged enema solution or suspension according to claim 18, wherein the chelating agent is one of the alkali metal salts of ethylene diaminetetraacetic acid. 
     
     
        .Iaddend. .Iadd.20.  A packaged enema solution or suspension according to claim 19, wherein the enema solution or suspension has a pH value of from 4.5 to 5. .Iaddend. .Iadd.21. A packaged enema solution or suspension according to claim 20, wherein the enema solution or suspension is a suspension. .Iaddend. .Iadd.22. A packaged enema solution or suspension consisting essentially of an effective amount of 5-ASA, an alkali metal salt of ethylene diaminetetraacetic acid, potassium pyrosulfite, and a buffer, said solution or suspension having a pH value of from 4 to 5 and being contained in a plastic bottle under an inert gas, said plastic bottle being packaged in a diffusion-tight light-impervious package in the same inert gas as is present in the bottle. .Iaddend. .Iadd.23. A packaged enema solution or suspension according to claim 22, wherein the enema solution or suspension has a pH value of from 4.5 to 5. .Iaddend. .Iadd.24. A packaged enema solution or suspension according to claim 22, wherein the enema solution or suspension has a pH value of about 4.8. .Iaddend. .Iadd.25. A packaged enema solution or suspension according to claim 22, containing per 100 ml of said solution or suspension about 50 mg 
     
     
        to 200 mg of potassium pyrosulfite. .Iaddend. .Iadd.26.  A packaged enema solution or suspension according to claim 25, wherein the enema solution or suspension is a suspension. .Iaddend.