Drug polymer complexes

• US 20070110804A1
• Filed: 06/18/2004
• Published: 05/17/2007
• Est. Priority Date: 06/20/2003
• Status: Abandoned Application

• Current Assignee: Royer Biomedical, Inc.
• Original Assignee: Royer Biomedical, Inc.
• Inventors: Royer, Garfield
• Application Number:
  US10/561,245
• Publication Number:
  US 20070110804A1
• Time in Patent Office: Days
• US Class Current: 424/468
• CPC Class Codes: A61K 47/36 Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
• CPC Class Codes: A61K 47/38 Cellulose; Derivatives thereof
• CPC Class Codes: A61K 47/61 the organic macromolecular compound being a polysaccharide or a derivative thereof
• CPC Class Codes: A61K 47/6949 inclusion complexes, e.g. clathrates, cavitates or fullerenes
• CPC Class Codes: A61K 9/0024 Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue compositions for intravenous administration, normal injectable solutions or dispersions for, e.g. subcutaneous administration A61K9/0019; brain implants A61K9/0085; (coated) prostheses, catheters or stents A61L
• CPC Class Codes: A61K 9/06 Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels composition of ointments, creams or gels A61K47/00
• CPC Class Codes: A61L 2300/402 Anaestetics, analgesics, e.g. lidocaine
• CPC Class Codes: A61L 2300/406 Antibiotics
• CPC Class Codes: A61L 2300/416 Anti-neoplastic or anti-proliferative or anti-restenosis or anti-angiogenic agents, e.g. paclitaxel, sirolimus
• CPC Class Codes: A61L 2300/602 Type of release, e.g. controlled, sustained, slow
• CPC Class Codes: A61L 2300/80 characterised by a special chemical form
• CPC Class Codes: A61L 2400/06 Flowable or injectable implant compositions
• CPC Class Codes: A61L 27/20 Polysaccharides
• CPC Class Codes: A61L 27/38 containing added animal cells organs or tissue containing native cells A61L27/36
• CPC Class Codes: A61L 27/54 Biologically active materials, e.g. therapeutic substances A61L27/227 takes precedence
• CPC Class Codes: B82Y 5/00 Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
• CPC Class Codes: C08L 1/26 Cellulose ethers
• CPC Class Codes: C08L 5/02 Dextran; Derivatives thereof

Abstract

This invention relates to polymeric complexes of drugs to be employed as (or in) sustained release-formulations comprising a cationic active agent, and a polyanionic water soluble complexing polymer of sufficient molecular weight that it forms a gel when mixed with said active agent. The invention also relates to the manufacture of such sustained release compositions and their many uses. Also included is a molded prosthesis comprising a prosthesis including a sustained release composition comprising a cationic anti-infective and a complexing polymer.

Claims

1. A sustained release composition comprising a cationic active agent, and a polyanionic water-soluble complexing polymer of sufficient molecular weight that it forms a gel when mixed with said active agent.

2. A composition as in claim 1 further comprising calcium sulfate.

3. A composition as in claim 1 further comprising a mixture of phosphates, which includes tricalcium phosphate.

4. A composition as in claim 1 further comprising hydroxyl apatite.

5. A composition as in claim 1 wherein said complexing polymer is at least two complexing polymers of different molecular weight.

6. A composition as in claim 1 wherein said active agent is an anti-infective selected from the group consisting of gentamicin, azithromycin, clarithromycin, doxycycline, minocycline and lincomycin, clindamycin, amikacin, vancomycin, tobramycin, nystatin, and amphotericin B.

7. A composition as in claim 1 wherein said active agent is an anesthetic selected from the group consisting of dibucaine, tetracaine, procaine, etidocaine, bupivacaine, mepivacaine, and prilocaine.

8. A composition as in claim 1 wherein said active agent is an opioid/analgesic selected from the group consisting of fentanyl, sufentenil, morphine, methadone, etorphine, levorphanol, levallorphan, butorphenol, buprenorphine, oxycodone, hydromorphone, propoxyphene, naloxone, naltrexone, nalorphine, nalbuphine, nalmefene, codeine, oxymorphone, and dermorphine.

9. A composition as in claim 1 wherein said active agent is an anti-tumor agent.

10. A composition as in claim 1 wherein said active agent is a CNS agent selected from the group consisting of acepromezine, prochlorperazine, clomipramine, ondansetron, sertraline, doxazosine, chlorpromazine, and atropine.

11. A composition as in claim 1 wherein said complexing polymer is selected from the group consisting of dextran sulfate, carboxymethylcellulose, and pentosan sulfate.

12. A composition as in claim 1 wherein said complexing polymer is dextran sulfate (Na).

13. A composition as in claim 12 wherein said complexing polymer is dextran sulfate (Na) of molecular weight 500,000 or higher.

14. A composition as in claim 1 wherein said complexing polymer is carboxymethylcellulose.

15. A composition as in claim 1 wherein said complexing polymer is L-carboxymethylcellulose.

16. A composition as in claim 1 wherein said complexing polymer is M-carboxymethylcellulose.

17. A method of treating an infection in a mammal comprising administering to said mammal a sustained release composition comprising a cationic anti-infective and a polyanionic water soluble complexing polymer of sufficient molecular weight that it forms a gel with said anti-infective.

18. A method of treating bone sepsis, joint sepsis, an infected joint prosthesis, a diabetic foot infection, or periodontal disease, in a mammal comprising administering by injection to said mammal a composition comprising active agent selected from the group consisting of gentamicin, azithromycin, clarithromycin, doxycycline, minocycline and lincomycin, clindamycin, amikacin, vancomycin, tobramycin, nystatin, and amphotericin B. and a complexing polymer of sufficient molecular weight that it forms a gel with said anti-infective.

19. A method of systemically treating an infection in a mammal comprising administering subcutaneously to said mammal a composition comprising active agent selected from the group consisting of gentamicin, azithromycin, clarithromycin, doxycycline, minocycline and lincomycin, clindamycin, amikacin, vancomycin, tobramycin, nystatin, and amphotericin B and a complexing polymer.

20. A method of regionally blocking nerves or treating localized pain in a mammal comprising administering by injection to said mammal a composition comprising an anesthetic selected from the group consisting of dibucaine, tetracaine, procaine, prilocaine, etidocaine, bupivacaine, mepivacaine, and a complexing polymer.

21. A method of treating pain in a mammal comprising administering to said mammal a composition comprising an active agent selected from the group consisting of oxycodone, morphine, fentanyl, sufentanil, and hydromorphone, and a complexing polymer.

22. A method as in claim 21 wherein said complexing polymer is at least two complexing polymers of different molecular weight.

23. A method of treating drug addiction in a mammal comprising administering to said mammal a composition comprising an active agent selected from the group consisting of methadone, buprenorphine, naloxone, and naltrexone, and a complexing polymer.

24. A method of treating cancer in a mammal comprising administering to said mammal a sustained release composition comprising a cationic anti-tumor agent and a polyanionic water soluble complexing polymer.

25. A molded prosthesis comprising a prosthesis including a sustained release composition comprising a cationic active agent selected from the group consisting of gentamicin, azithromycin, clarithromycin, doxycycline, minocycline and lincomycin, clindamycin, amikacin, vancomycin, tobramycin, nystatin, and amphotericin B., and a polyanionic water soluble complexing polymer of sufficient molecular weight that it forms a gel with said active agent.

26. A method of producing a sustained release gel composition comprising mixing a cationic active agent and a polyanionic water soluble complexing polymer of sufficient molecular weight that it forms a gel with said active agent.

27. A method of producing a sustained release composition comprising mixing a cationic active agent and a polyanionic water soluble complexing polymer of sufficient molecular weight that it forms a gel with said active agent, drying the gel, grinding the dried gel to a powder, and suspending the powder in a suspending agent.

28. A method of producing a sustained release composition comprising mixing a cationic active agent and a polyanionic water soluble complexing polymer of sufficient molecular weight that it forms a gel with said active agent, and adding calcium sulfate to the gel.

29. A method as in claim 28 wherein the calcium sulfate is calcium sulfate hemihydrate.

30. A method as in claim 28 wherein the calcium sulfate is calcium sulfate dihydrate.

31. A composition comprising a mixture of at least two polymer-drug complexes each of which contains a distinct active ingredient.

32. A composition comprising a solid polymer drug complex suspended in a liquid polymer-drug complex.

33. A composition comprising a polymeric anion with a poorly soluble cationic drug complex of low molecular weight.

34. A composition comprising a neutral drug entrapped within a cross-linked reaction product of a polymeric anion and a cation cross-linking agent.