Sequential administration of partitioned absorption aspirin or active aspirin derivative and cox-2 inhibitor

Abstract

Described herein are an aspirin or active aspirin derivative and a COX-2 inhibitor, at least one of which has an enteric or partial enteric coating, administered in combination yet delivered sequentially, for the treatment and prophylactic treatment of diseases, symptoms and conditions. In some embodiments, the COX-2 inhibitor has the enteric coating; however, the aspirin or active aspirin derivative may additionally or alternately have the enteric coating. In all embodiments, the drug having the enteric coating or enteric formulation is targeted for absorption in the small intestine or colon, or both the small intestine and the colon.

What is claimed is: 
     
         1 . A method of treating or prophylactically treating a patient for conditions known to precipitate inflammation with or without fever comprising giving the patient a single composite dosage unit having partitioned sequential bioabsorption, the single composite dosage unit comprising i) an aspirin or active aspirin derivative, and ii) a COX-2 inhibitor for partitioned sequential absorption, at least one of which has an enteric or partial enteric coating for onset of action and bioabsorption in a small intestine or colon and the other for rapid onset of action and absorption in a gastric area, or a duodenal area, or both areas. 
     
     
         2 . The method of  claim 1 , wherein the aspirin or active aspirin derivative comprises a) acetylsalicylic acid or any of its active derivatives that can release salicylate in vivo, and b) pharmaceutically acceptable amounts of inert fillers and binders, and provide anti-platelet effect. 
     
     
         3 . The method of  claim 1 , wherein the enteric or partial enteric coating comprises one or more coatings selected from the group consisting of polymethacrylates, cellulose ester polymers, cellulose acetate trimellitate, hydroxypropyl methyl cellulose phthalate, hydroxypropyl methyl cellulose acetate succinate, polyvinyl derivatives, methacrylic acid copolymers, acrylic copolymers, or a mixture of sodium alginate and aqueous ammonium salt in shellac. 
     
     
         4 . The method of  claim 1 , wherein the administering of the aspirin or active aspirin derivative and the COX-2 inhibitor is short-term. 
     
     
         5 . The method of  claim 1 , wherein the administering of the aspirin or active derivative of aspirin and the COX-2 inhibitor is periodic. 
     
     
         6 . The method of  claim 1 , wherein the aspirin or active derivative of aspirin comprises at least one of ASA, PC-ASA, PL2200, PA8140, and PA32540. 
     
     
         7 . The method of  claim 1 , wherein the COX-2 inhibitor comprises celecoxib, celecoxib analogue, PC-celecoxib, or PC-celecoxib analogue. 
     
     
         8 . A method of treating or prophylactically treating a patient comprising giving the patient a composite single dosage unit having no outer enteric coating and having partitioned sequential bioabsorption, the composite single dosage unit comprising a combination of a COX-2 inhibitor for onset of action and absorption in a gastric area, or a duodenal area or both areas, and a non-enteric aspirin or active aspirin derivative having an enteric coating for sequential separation of bioabsorption of the aspirin or active aspirin derivative from bioabsorption of the COX-2 inhibitor for onset of action and absorption in a small intestine or colon, and for delayed distal release. 
     
     
         9 . The method of  claim 8 , wherein the non-enteric aspirin or active aspirin derivative consists of acetylsalicylic acid or any of its active derivatives that can release salicylate in vivo, and an enteric coating selected from one or more coatings comprising polymethacrylates, cellulose ester polymers, cellulose acetate trimellitate, hydroxypropyl methyl cellulose phthalate, hydroxypropyl methyl cellulose acetate succinate, polyvinyl derivatives, methacrylic acid copolymers, acrylic copolymers, or a mixture of sodium alginate and aqueous ammonium salt in shellac, and pharmaceutically acceptable amounts of inert fillers and binders. 
     
     
         10 . The method of  claim 8 , wherein the aspirin or active derivative of aspirin comprises at least one of ASA, PC-ASA, PL2200, PA8140, and PA32540. 
     
     
         11 . The method of  claim 8 , wherein the COX-2 inhibitor comprises celecoxib, celecoxib analogue, PC-celecoxib, or PC-celecoxib analogue. 
     
     
         12 . The method of  claim 8 , wherein the administering of the aspirin or active aspirin derivative and the COX-2 inhibitor is short-term. 
     
     
         13 . The method of  claim 8 , wherein the administering of the aspirin or active derivative of aspirin and the COX-2 inhibitor is periodic. 
     
     
         14 . The method of  claim 8 , wherein bioabsorption of the aspirin or active derivative of aspirin occurs in the small intestine. 
     
     
         15 . The method of  claim 8 , wherein the coating is pH-sensitive, time-sensitive, and/or microflora-activated. 
     
     
         16 . A kit comprising an aspirin or active aspirin derivative and a COX-2 inhibitor for partitioned sequential absorption, at least one of which has an enteric or partial enteric coating for onset of action and bioabsorption in a small intestine or colon and the other for rapid onset of action and absorption in a gastric area, or a duodenal area, or both areas. 
     
     
         17 . The kit of  claim 16 , wherein the COX-2 inhibitor has the enteric or partial enteric coating. 
     
     
         18 . The kit of  claim 16 , wherein the aspirin or active aspirin derivative has the enteric or partial enteric coating. 
     
     
         19 . The kit of  claim 16 , wherein the enteric or partial enteric coating is one or more coatings comprising polymethacrylates, cellulose ester polymers, cellulose acetate trimellitate, hydroxypropyl methyl cellulose phthalate, hydroxypropyl methyl cellulose acetate succinate, polyvinyl derivatives, methacrylic acid copolymers, acrylic copolymers, or a mixture of sodium alginate and aqueous ammonium salt in shellac. 
     
     
         20 . The kit of  claim 16 , wherein the coating is aqueous-based or solvent-based.