Compositions and methods for increasing the oral absorption of antimicrobials

• US 7,527,807 B2
• Filed: 06/22/2001
• Issued: 05/05/2009
• Est. Priority Date: 06/21/2000
• Status: Expired due to Fees

• Current Assignee: International Health Management Associates, Cubist Pharmaceuticals, LLC (Merck & Co., Inc.), University of Utah (State of Utah)
• Original Assignee: Cubist Pharmaceuticals, Inc. (Merck & Co., Inc.)
• Inventors: Lee, Jeoung-Soo, Choi, Seung-Ho, Keith, Dennis
• Primary Examiner(s): Lucas; Zachariah
• Application Number:
  US09/888,114
• Publication Number:
  US 20030039956A1
• Time in Patent Office: 2,874 Days
• Field of Search: 424/464, 424/484, 424/485, 424/487, 424/488, 424/497, 424/10, 424/147, 424/295, 424/489, 424/490, 424/499, 514/772.3, 514/773, 514/779, 514/784, 514/188, 514/200, 514/206, 514/546, 514/777, 536/20, 536/103, 435/5
• US Class Current: 424/488
• CPC Class Codes: A61K 47/61 the organic macromolecular compound being a polysaccharide or a derivative thereof
• CPC Class Codes: A61K 9/1652 Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin homeopathic globules A61K9/1623

Abstract

The present invention provides compositions and methods for increasing absorption of antibacterial agents, particularly third generation cephalosporin antibacterial agents, in oral dosage solid and/or suspension forms. Specifically, the composition is comprised of a biopolymer that is preferably swellable and/or mucoadhesive, a antimicrobial agent, and a cationic binding agent contained within the biopolymer such that the binding agent is tonically bound or complexed to at least one member selected from the group consisting of the biopolymer and the antimicrobial agent.

Claims

1. A pharmaceutical composition for oral delivery of a cephalosporin comprising:

a) a composition consisting of;

(i) carrageenan;

(ii) at least one cephalosporin entrained within or ionically bound to the biopolymer;

(iii) at least one metal cation entrained within or ionically bound to the biopolymer or the cephalosporin; and

b) an absorption enhancer.

2. The pharmaceutical composition of claim 1 wherein the cephalosporin is selected from the group consisting of ceftiofur, cefipime, cefixime, cefoperazone, cefotaxime, cefpodoxime, ceftazidime, ceftizoxime, ceftriaxone, cefpirome, cefclidin, cefmenoxime, cefozopran, and combinations thereof.

3. The pharmaceutical composition of claim 2 wherein the cephalosporin is ceftriaxone.

4. The pharmaceutical composition of claim 1 wherein the metal cation is selected from the group consisting of calcium, magnesium, lithium, iron, copper, zinc, aluminum, manganese, chromium, cobalt, nickel, and combinations thereof.

5. The pharmaceutical composition of claim 3 wherein the metal cation is calcium.

6. The pharmaceutical composition of claim 3 wherein the metal cation is zinc.

7. The pharmaceutical composition of claim 1 wherein the metal cation is ionically bound to the carrageenan forming a metal cation-carrageenan complex and the cephalosporin is contained within the metal cation-canageenan complex.

8. The pharmaceutical composition of claim 1 wherein the metal cation is ionically bound to the cephalosporin forming a metal cation-cephalosporin complex and the metal cation-cephalosporin complex is contained within the carrageenan.

9. The pharmaceutical composition of claim 1 wherein the metal cation is complexed to the cephalosporin and the metal cation is further ionically bound to the canageenan forming a cephalosporin-metal cation-carrageenan bridge.

10. The pharmaceutical composition of claim 5 wherein the carrageenan has a calcium content of less than about 0.4% by weight.

11. The pharmaceutical composition of claim 1 wherein the cephalosporin is ceftriaxone, the metal cation is calcium and the absorption enhancer is a non-ionic surfactant.

12. The pharmaceutical composition of claim 1, wherein the cephalosporin is a third generation cephalosporin.