IP Library Granted Patent US 11,998,586
Granted Patent B2
US 11,998,586 · App. 17/525,344 · Granted Jun 4, 2024

Compositions comprising antimicrobial peptides

Inventors: Kenneth Urish (Sewickley, PA); Jonathan Brendan Mandell (Pittsburgh, PA)
Assignee: University of Pittsburgh—Of the Commonwealth System of Higher Education
A61K38/10A61K31/546A61K38/1729
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Quick Facts
Patent No.
US 11,998,586
App. No.
17/525,344
Granted
Jun 4, 2024
Kind
B2
Abstract

A method of treating or preventing a microbial infection in a patient is provided, along with a wound irrigation system and a composition in the form of an irrigation liquid for reducing microbial load or preventing microbial infection in a wound.

Claims (87)

1. A method of treating or preventing an infection in a subject in need thereof, comprising administering a pharmaceutical composition to an open wound, an implant, a medical device, a prosthetic, or any part thereof of the subject, wherein the infection comprises a biofilm, thereby treating or preventing the infection, wherein the pharmaceutical composition comprises:

a. a cationic antimicrobial peptide or pharmaceutically acceptable salt thereof, wherein the cationic antimicrobial peptide is SEQ ID NO: 10; and

b. a pharmaceutically acceptable aqueous carrier;

wherein the pharmaceutical composition is in the form of a liquid; wherein the cationic antimicrobial peptide is present at a concentration of about 3 mg/mL to about 30 mg/mL, and wherein the pharmaceutical composition has a total osmolarity from about 50 mOsm/L to about 350 mOsm/L.

2. The method of claim 1 , wherein the pharmaceutical composition further comprises a salt that is selected from the group consisting of sodium chloride, potassium chloride, potassium dihydrogen phosphate, disodium phosphate, calcium chloride, sodium lactate, copper chloride, copper sulfate, C 11 H 22 CuO 14 , ammonium hydroxide, magnesium hydroxide, sodium carbonate, and any combination thereof.

3. The method of claim 1 , wherein the pharmaceutical composition further has a pH of from about 7.2 to about 8.0.

4. The method of claim 1 , wherein the administering comprises irrigating the open wound, the implant, the medical device, the prosthetic, or any part thereof using the pharmaceutical composition.

5. The method of claim 4 , wherein the irrigating further comprises reducing microbe load, wherein the microbe load is reduced by at least 1000-fold when the irrigating lasts for at most about 30 minutes.

6. The method of claim 1 , wherein the treating or preventing the infection further comprises administering an antibiotic to the subject in need thereof.

7. The method of claim 1 , wherein the aqueous carrier comprises water, normal saline, phosphate buffered saline, dextrose, glycerol, ethanol, buffered salt solutions, lactated Ringer's solution, or any combination thereof.

8. The method of claim 1 , wherein the pharmaceutical composition further has a pH of from about 5.0 to about 8.0.

9. The method of claim 1 , wherein the pharmaceutical composition further has a pH from about 7.4 to about 8.0.

10. The method of claim 1 , wherein the infection comprises a bacteria species comprising Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter species, Escherichia coli , or any combination thereof.

11. The method of claim 1 , wherein the infection comprises periprosthetic joint infection.

12. The method of claim 1 , wherein the method is subsequent to an irrigation and debridement (I&D) of the open wound, the implant, the medical device, the prosthetic, or any part thereof, wherein said I&D comprises use of a betadine, a chlorohexidine, or saline solution.

13. The method of claim 1 , further comprising administering an antibiotic selected from the group consisting of: Aminoglycoside, Carbapenem, Ceftazidime, Cefepime, Ceftobiprole, Ceftaroline, Clindamycin, Cefazolin, Dalbavancin, Daptomycin, Fluoroquinolone, Linezolid, Mupirocin, Oritavancin, Piperacillin, Silver nitrate, Streptogramin, Telavancin, Tedizolid, Ticarcillin, Tigecycline, Vancomycin, and any combination thereof.

14. The method of claim 1 , wherein the method reduces a bacterial burden of the biofilm by at least 10 2 CFU/mL as determined by a CFU quantification assay compared to an untreated subject.

15. The method of claim 1 , wherein the method reduces a bacterial burden of the biofilm by at least a three-log reduction as determined by a CFU quantification assay compared to an untreated subject.

16. The method of claim 1 , wherein the method reduces a bacterial burden of the biofilm by 99.9%.

17. A method of treating or preventing an infection in a subject in need thereof, comprising irrigating an open wound, an implant, a medical device, a prosthetic, or any part thereof of the subject using a pharmaceutical composition, wherein the infection comprises a biofilm, thereby treating or preventing the infection, wherein the pharmaceutical composition comprises:

a. a cationic antimicrobial peptide or pharmaceutically acceptable salt thereof, wherein the cationic antimicrobial peptide is SEQ ID NO: 10, and wherein the cationic antimicrobial peptide is present at a concentration of about 3 mg/mL to about 30 mg/mL; and

b. a pharmaceutically acceptable aqueous carrier;

wherein the pharmaceutical composition is in the form of a liquid; and wherein the irrigating is performed at least once a day.

18. The method of claim 17 , wherein the cationic antimicrobial peptide is present at a concentration of about 10 mg/mL.

19. The method of claim 17 , wherein the aqueous carrier comprises water, normal saline, phosphate buffered saline, dextrose, glycerol, ethanol, buffered salt solutions, lactated Ringer's solution, or any combination thereof.

20. The method of claim 17 , wherein the pharmaceutical composition further has a pH of from about 5.0 to about 8.0.

21. The method of claim 17 , wherein the pharmaceutical composition further has a pH from about 7.2 to about 8.0.

22. The method of claim 17 , wherein the infection comprises a bacteria species comprising Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter species, Escherichia coli , or any combination thereof.

23. The method of claim 17 , wherein the infection comprises periprosthetic joint infection.

24. The method of claim 17 , wherein the method is subsequent to an irrigation and debridement (I&D) of the open wound, the implant, the medical device, the prosthetic, or any part thereof, wherein said I&D comprises use of a betadine, a chlorohexidine, or saline solution.

25. A method of treating or preventing an infection in a subject in need thereof, comprising irrigating an open wound, an implant, a medical device, a prosthetic, or any part thereof of the subject using a pharmaceutical composition, wherein the infection comprises a biofilm, thereby treating or preventing the infection, wherein the pharmaceutical composition comprises:

a. a cationic antimicrobial peptide or pharmaceutically acceptable salt thereof, wherein the cationic antimicrobial peptide is SEQ ID NO: 10, and wherein the cationic antimicrobial peptide is present at a concentration of about 3 mg/mL to about 30 mg/mL; and

b. a pharmaceutically acceptable aqueous carrier;

wherein the pharmaceutical composition is in the form of a liquid; and wherein the irrigating using the pharmaceutical composition is performed for a period ranging from about 0.1 min to about 30 min.

26. The method of claim 25 , wherein the irrigating using the pharmaceutical composition is performed for a period of about 15 min.

27. The method of claim 25 , wherein the cationic antimicrobial peptide is present at a concentration of about 10 mg/mL.

28. The method of claim 25 , wherein the aqueous carrier comprises water, normal saline, phosphate buffered saline, dextrose, glycerol, ethanol, buffered salt solutions, lactated Ringer's solution, or any combination thereof.

29. The method of claim 25 , wherein the pharmaceutical composition further has a pH of from about 5.0 to about 8.0.

30. The method of claim 25 , wherein the pharmaceutical composition further has a pH from about 7.2 to about 8.0.

31. The method of claim 25 , wherein the infection comprises a bacteria species comprising Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter species, Escherichia coli , or any combination thereof.

32. The method of claim 25 , wherein the infection comprises periprosthetic joint infection.

33. The method of claim 25 , wherein the method is subsequent to an irrigation and debridement (I&D) of the open wound, the implant, the medical device, the prosthetic, or any part thereof, wherein said I&D comprises use of a betadine, a chlorohexidine, or saline solution.

34. A method of treating or preventing an infection in a subject in need thereof, comprising administering a pharmaceutical composition to an open wound, an implant, a medical device, a prosthetic, or any part thereof of the subject, wherein the infection comprises a biofilm, thereby treating or preventing the infection, wherein the pharmaceutical composition comprises:

a. a cationic antimicrobial peptide or pharmaceutically acceptable salt thereof, wherein the cationic antimicrobial peptide is SEQ ID NO: 10, and wherein the cationic antimicrobial peptide is present at a concentration of about 3 mg/mL to about 30 mg/mL; and

b. a pharmaceutically acceptable aqueous carrier;

wherein the pharmaceutical composition is in the form of a liquid, and wherein the pharmaceutical composition is physiologically isotonic or physiologically hypotonic.

35. The method of claim 34 , wherein the pharmaceutical composition is physiologically isotonic.

36. The method of claim 34 , wherein the pharmaceutical composition is physiologically hypotonic.

37. The method of claim 34 , wherein the aqueous carrier comprises water, normal saline, phosphate buffered saline, dextrose, glycerol, ethanol, buffered salt solutions, lactated Ringer's solution, or any combination thereof.

38. The method of claim 34 , wherein the cationic antimicrobial peptide is present at a concentration of about 10 mg/mL.

39. The method of claim 34 , wherein the pharmaceutical composition further has a pH of from about 5.0 to about 8.0.

40. The method of claim 34 , wherein the pharmaceutical composition further has a pH from about 7.2 to about 8.0.

41. The method of claim 34 , wherein the infection comprises a bacteria species comprising Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter species, Escherichia coli , or any combination thereof.

42. The method of claim 34 , wherein the infection comprises periprosthetic joint infection.

43. The method of claim 34 , wherein the method is subsequent to an irrigation and debridement (I&D) of the open wound, the implant, the medical device, the prosthetic, or any part thereof, wherein said I&D comprises use of a betadine, a chlorohexidine, or saline solution.

44. A method of treating or preventing an infection in a subject in need thereof, comprising administering a pharmaceutical composition to an open wound, an implant, a medical device, a prosthetic, or any part thereof of the subject, wherein the infection comprises a biofilm, thereby treating or preventing the infection, wherein the pharmaceutical composition comprises:

a. a cationic antimicrobial peptide or pharmaceutically acceptable salt thereof, wherein the cationic antimicrobial peptide is SEQ ID NO: 10, and wherein the cationic antimicrobial peptide is present at a concentration of about 3 mg/mL to about 30 mg/mL; and

b. a pharmaceutically acceptable aqueous carrier;

wherein the pharmaceutical composition is in the form of a liquid; and wherein the pharmaceutical composition comprises a total ionic strength from about 0.02 M to about 0.2 M.

45. The method of claim 44 , wherein the cationic antimicrobial peptide is present at a concentration of about 10 mg/mL.

46. The method of claim 44 , wherein the aqueous carrier comprises water, normal saline, phosphate buffered saline, dextrose, glycerol, ethanol, buffered salt solutions, lactated Ringer's solution, or any combination thereof.

47. The method of claim 44 , wherein the pharmaceutical composition further has a pH of from about 5.0 to about 8.0.

48. The method of claim 44 , wherein the pharmaceutical composition further has a pH from about 7.2 to about 8.0.

49. The method of claim 44 , wherein the infection comprises a bacteria species comprising Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter species, Escherichia coli , or any combination thereof.

50. The method of claim 44 , wherein the infection comprises periprosthetic joint infection.

51. The method of claim 44 , wherein the method is subsequent to an irrigation and debridement (I&D) of the open wound, the implant, the medical device, the prosthetic, or any part thereof, wherein said I&D comprises use of a betadine, a chlorohexidine, or saline solution.

52. A method of treating or preventing an infection in a subject in need thereof, comprising administering a pharmaceutical composition to an open wound, an implant, a medical device, a prosthetic, or any part thereof of the subject, wherein the infection comprises a biofilm, thereby treating or preventing the infection, wherein the pharmaceutical composition comprises:

a. a cationic antimicrobial peptide or pharmaceutically acceptable salt thereof, wherein the cationic antimicrobial peptide is SEQ ID NO: 10, and wherein the cationic antimicrobial peptide is present at a concentration of about 10 mg/mL; and

b. a pharmaceutically acceptable aqueous carrier;

wherein the pharmaceutical composition is in the form of a liquid.

53. The method of claim 52 , wherein the aqueous carrier comprises water, normal saline, phosphate buffered saline, dextrose, glycerol, ethanol, buffered salt solutions, lactated Ringer's solution, or any combination thereof.

54. The method of claim 52 , wherein the pharmaceutical composition further has a pH of from about 5.0 to about 8.0.

55. The method of claim 52 , wherein the pharmaceutical composition further has a pH from about 7.2 to about 8.0.

56. The method of claim 52 , wherein the infection comprises a bacteria species comprising Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter species, Escherichia coli , or any combination thereof.

57. The method of claim 52 , wherein the infection comprises periprosthetic joint infection.

58. The method of claim 52 , wherein the method is subsequent to an irrigation and debridement (I&D) of the open wound, the implant, the medical device, the prosthetic, or any part thereof, wherein said I&D comprises use of a betadine, a chlorohexidine, or saline solution.

59. A method of treating or preventing an infection in a subject in need thereof, comprising injecting a pharmaceutical composition to an open wound, an implant, a medical device, a prosthetic, or any part thereof of the subject, thereby treating or preventing the infection, wherein the pharmaceutical composition comprises:

a. a cationic antimicrobial peptide or pharmaceutically acceptable salt thereof, wherein the cationic antimicrobial peptide is SEQ ID NO: 10, and wherein the cationic antimicrobial peptide is present at a concentration of about 3 mg/mL to about 30 mg/mL; and

b. a pharmaceutically acceptable aqueous carrier;

wherein the pharmaceutical composition is in the form of a liquid.

60. The method of claim 59 , wherein the cationic antimicrobial peptide is present at a concentration of about 10 mg/mL.

61. The method of claim 59 , wherein the aqueous carrier comprises water, normal saline, phosphate buffered saline, dextrose, glycerol, ethanol, buffered salt solutions, lactated Ringer's solution, or any combination thereof.

62. The method of claim 59 , wherein the pharmaceutical composition further has a pH of from about 5.0 to about 8.0.

63. The method of claim 59 , wherein the pharmaceutical composition further has a pH from about 7.2 to about 8.0.

64. The method of claim 59 , wherein the infection comprises a bacteria species comprising Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter species, Escherichia coli , or any combination thereof.

65. The method of claim 59 , wherein the infection comprises periprosthetic joint infection.

66. The method of claim 59 , wherein the method is subsequent to an irrigation and debridement (I&D) of the open wound, the implant, the medical device, the prosthetic, or any part thereof, wherein said I&D comprises use of a betadine, a chlorohexidine, or saline solution.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 20, 2022
From: URISH, KENNETH; MANDELL, JONATHAN BRENDAN
To: UNIVERSITY OF PITTSBURGH - OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION
Reel/Frame 059973/0419 →
Continuity (4)
Continuation PCTUS2020059415 · Nov 6, 2020
Provisional Application 63028636 · May 22, 2020
Provisional Application 62932609 · Nov 8, 2019
Related Publication 20220054589A1 · Feb 24, 2022