Chemotherapeutic treatment of bacterial infections with an antibiotic encapsulated within a biodegradable polymeric matrix

• US 6,410,056 B1
• Filed: 05/22/1995
• Issued: 06/25/2002
• Est. Priority Date: 03/16/1984
• Status: Expired due to Fees

• Current Assignee: United States Department Of Health And Human Services (Government of the United States of America)
• Original Assignee: The United States Of America As Represented By The Secretary Of The Army
• Inventors: Tice, Thomas R., Setterstrom, Jean A., Jacob, Elliot
• Primary Examiner(s): Page, Thurman K.
• Assistant Examiner(s): HOWARD, SHARON LEE
• Application Number:
  US08/446,148
• Time in Patent Office: 2,591 Days
• Field of Search: 424/78.1, 424/457, 424/462, 424/501, 424/502, 549/274, 428/402.21, 514/772.3
• US Class Current: 424/501
• CPC Class Codes: A61K 9/1647 Polyesters, e.g. poly(lactide-co-glycolide)
• CPC Class Codes: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
• CPC Class Codes: Y10T 428/2989 Microcapsule with solid core [includes liposome]

Abstract

Biodegradable pharmaceutical compositions and method for treating bacterial infections therein.

Claims

1. A method for the protection against or therapeutic treatment of bacterial infection in the tissue of a human or nonhuman animal comprising administering locally to said animal a bactericidally-effective amount of a pharmaceutical composition consisting essentially of an antibiotic encapsulated within a biodegradable comprising poly (DL-lactide-co-glycolide) matrix wherein the duration of controlled release of the antibiotic is within a period of about 14 days to about 6 weeks.

2. The method according to claim 1 wherein the biodegradable Polymeric matrix is a poly (DL-lactide-co-glycolide having a relative ratio between the amount of lactide and glycolide component within th e range of 40:

60 to 100;

0.

3. A method according to claim 1 wherein the bacterial infection is (1) a subcutaneous infection secondary to contaminated abdominal surgery, (2) an infection surrounding prosthetic devices and vascular grafts, (3) ocular infections, (4) topical skin infections, (5) orthopedic infections, including osteomyelitis, and (6) oral infections.

4. The method according to claim 3 wherein the oral infections are pericoronitis or periodontal disease.

5. The method according to claim 1 wherein the administration is effected prior to infection.

6. The method according to claim 1 wherein the administration is effected subsequent to infection.

7. The method according to claim 1 wherein said animal is a human.

8. The method according to claim 1 wherein said animal is a nonhuman.

9. The method in accordance with claim 1 comprising applying to the soft tissue or bone tissue of said animal a bactericidally-effective amount of a pharmaceutical composition consisting essentially of an antibiotic in the amount of 5 to 60 percent, selected from the group consisting essentially of a beta-lactam, aminoglycolide, polymyxin-B, Amphotericin B, Aztreonam, cephalosporins, chloramphenicol, fusidans, lincosamides, macrolides, methronidazole, nitro-furation, Imipenem/cilastin, quinolones, refampin, polyenes, tetracycline, sulfonamides, trimethoprim, vancomycin, teicoplanin, imidazoles, and erythromycin, encapsulated within a biodegradable poly(DL-lactide-co-glycolide) polymeric matrix, wherein the amount of the lactide component is within the range of 48 to 58 glycolide component is within the range of 52 to 42 based on the weight of said polymeric matrix which is present in the amount of from 40 to 95 percent, resulting in the controlled release of a bacteriacidal amount of the said antibiotic over a period of about 14 days to about 6 weeks.

10. The method of claim 2 wherein the polymeric matrix consists essentially of a poly(DL-lactide-co-glycolide) wherein the relative ratio between the amount of lactide and glycolide component is within the range of 48:

52 to 58;

42.

11. The method of claim 9 wherein the bacterial infection is caused by a resistant or non-resistant bacteria selected from the group consisting essentially of Enterobacteriaceae;

Klebsiella sp.;

Bacteroides sp.;

Enterococci;

Proteus sp.;

Streptococcus sp.;

Staphylococcus sp;

Pseudomonas sp.;

Neisseria sp.;

Pedptostreptococcus sp.;

Fusobacterium sp.;

Actinomyces sp.;

Mycobacterium sp.;

Listeria sp.;

Corynebacterium sp.;

Proprionibacterium sp.;

Actinobacillus sp.;

Aerobacter sp.;

Borrelia sp.;

Campylobacter sp.;

Cytophaga sp.;

Pasteurella sp.;

Clostridium sp., Enterobacter aerogenes, Peptococcus sp., Proteus vulgaris, Proteus morganii, Staphylococcus aureus, Streptococcus pyogenes, Actinomyces sp., Campylobacter fetus, and Legionella pneumophila. Ampicillin-resistant strain of S. aureus and methicillin-resistant strain of S. aureus.

12. The method of claim 10 wherein the antibiotic is selected from the group consisting essentially of a beta-lactam, aminoglycolide, polymyxin-B, amphotericin B, aztreonam, cephalosporins, chloramphenicol, fusidans, lincosamides, maacrolides, methronidazole, nitro-furantoin, Imipenem/cilastin, quinolones, rifampin, polyenes, tetracycline, sulfonamides, trimethoprim, vancomycin, teicoplanin, imidazoles, and erythromycin.

13. The method of claim 12 wherein the beta-lactam is selected from the group consisting essentially of penicillin and cephalosporin.

14. The method of claim 13 wherein the beta-lactam is cephalosporin.

15. The method of claim 13 wherein the beta-lactam is penicillin.

16. The method of claim 12 wherein the aminoglycolide is gentamicin.

17. The method of claim 12 wherein the aminoglycolide is amikacin.

18. The method of claim 12 wherein the aminoglycolide is tobramycin.

19. The method of claim 12 wherein the aminoglycolide is kanamycin.

20. The method of claim 13 wherein the beta-lactam is an ampicillin.

21. The method of claim 20 wherein the polymeric matrix consists essentially of a poly(DL-lactide-co-glycolide) wherein the relative ratio between the amount of lactide and glycolide component is within the range of 48:

52 to 58;

42.

22. The method of claim 20 wherein the ampicillin is present in an amount of from 5 to 60 percent and the amount of polymeric matrix is from 40 to 95 percent.

23. The method of claim 22 wherein the amount of ampicillin is 30 to 40 percent and the amount of the poly(DL-Lactide-co-glycolide) is 60 to 70 percent.

24. The method of claim 23 wherein the relative ratio between the amount of lactide and glycolide component is 53:

47.

25. The method of claim 13 wherein the beta-lactam is a cefazolin.

26. The method of claim 25 wherein the polymeric matrix consists essentially of a poly(DL-lactide-co-glycolide) wherein the relative ratio between the amount of lactide and glycolide component is within the range of 48:

52 to 58;

42.

27. The method of claim 25 wherein the cefazolin is present in an amount of from 5 to 60 percent and the amount of polymeric matrix is from 40 to 95 percent.

28. The method of claim 27 wherein the amount of ampicillin is 30 to 40 percent and the amount of the poly(DL-Lactide-co-glycolide) is 60 to 70 percent.

29. The method of claim 28 wherein the relative ratio between the amount of lactide and glycolide component is 53:

47.

31. The pharmaceutical composition according to claim 25 comprising an antibiotic in the amount of 5 to 60 percent, selected from the group consisting essentially a beta-lactam, aminoglycolide, polymyxin-B, amphotericin B, azetreonam, cephalosporins, chloramphenicol, fusiduns, lincosamides, macrolides, methronidazole, nitro-fuation, Impenem/cilastin, quinolones, refampin, polyenes, tetracycline, sulfonamides, trimethoprim, vancomycin, teicoplanin, imidazoles, and erythromycin, encapsulated within a biodegradable poly(DL-lactide-co-glycolide) polymeric matrix, wherein the amount of the lacide component is within the range of 48 to 58 glycolide component is within the range of 52 to 42 based on the weight of said polymeric matrix which is present in the amount of from 40 to 95 percent, resulting in the controlled release of a bactericidal amount of said antibiotic over a period of about 14 days to about 6 weeks.

32. The composition of claim 31 wherein the bacteria is selected from the group consisting essentially of Enterobacteriaceae;

Klebsiella sp.;

Bacteroides sp.;

Enterococci;

Proteus sp.;

Streptococcus sp.;

Staphylococcus sp.;

Pseudomonas sp.;

Neisseria sp.;

PedDtostreptococcus sp.;

Fusobacterium sp.;

Actinomyces sp.;

Mycobacterium sp.;

Listeria sp.;

Corynebacterium sp.;

Proprionibacterium sp.;

Actinobacillus sp.;

Aerobacter sp.;

Borrelia sp.;

Campylobacter sp.;

Cytophaga sp.;

Pasteurella sp.;

Clostridium sp., Enterobacter aerogenes, Peptococcus sp., Proteus vulgaris, Proteus morganii, Staphylococcus aureus, Streptococcus pryocgenes, Actinomyces sp., Camplobacter fetus, and Legionella Pneumophila.

33. The composition of claim 32 wherein the antibiotic is selected from the group consisting essentially of a beta-lactam, aminoglycolide, polymyxin-B, amphotericin B, Aztreonam, cephalosporins, chloramphenicol, fusidans, lincosamides, macrolides, methronidazole, nitro-furantion, imipenem/cilastin, quinolones, rifampin, polyenes, tetracycline, sulfonamides, trimethoprim, vancomycin, teicoplanin, imidazoles, and erythromycin.

34. The composition of claim 33 wherein the beta-lactam is selected from the group consisting essentially of penicillin and cephalosporin.

35. The composition of claim 33 wherein the beta-lactam is cephalosporin.

36. The composition of claim 33 wherein the beta-lactam is penicillin.

37. The composition of claim 33 wherein the aminoglycolide is gentamicin.

38. The composition of claim 33 wherein the aminoglycolide is amikacin.

39. The composition of claim 33 wherein the aminoglycolide is tobramycin.

40. The composition of claim 33 wherein the aminoglycolide is kananycin.

41. The composition of claim 33 wherein the beta-lactam is a ampicillin.

42. The composition of claim 33 wherein the beta-lactam is cefazolin.

43. The composition of claim 41 wherein the polymeric matrix consists essentially of a poly(DL-lactide-co-glycolide) wherein the relative ratio between the amount of the lactide and glycolide component is within the range of 48:

52 to 58;

42.

44. The composition of claim 43 wherein the amount of ampicillin is from 5 to 60 percent and the amount of polymeric matrix is from 40 to 95 percent.

45. The composition of claim 44 wherein the amount of ampicillin is 30 to 40 percent and the amount of the poly(DL-lactide-co-glycolide) is 60 to 70 percent.

46. The composition of claim 45 wherein the relative ratio between the amount of lactide and glycolide component is 53:

47.

47. The composition of claim 45 wherein the ampicillin is ampicillin anhydrate.

30. A pharmaceutical composition useful in the effective treatment of an animal with infected wound in the soft-tissue a bone consisting essentially of an antibiotic encapsulated within a biodegradable comprising poly (DL-lactide-co-glycolide) matrix wherein the controlled release rate of the antibiotic is within a period of about 14 days to about 6 weeks.