Composition comprising amino acid polymers and a bioactive agent and method of preparing thereof
A method of treating, reducing or preventing bacterial infection in a wound, the method comprising: applying a film on the wound, the film including a biodegradable polymer with bacteriophages dispersed therein, wherein the polymer is a poly (ester amide urea).
1. A method of treating, reducing or preventing bacterial infection in a wound, the method comprising: applying a flexible film on the wound, the film including a biodegradable polymer with bacteriophages dispersed therein, wherein the polymer is a poly (ester amide urea) comprising the following two blocks with random distribution thereof:
wherein
the ratio of l:m ranges from 0.01:0.99 to 0.99:0.01, l+m=1,
R 1 is chosen from C 1 -C 12 alkylene optionally interrupted by at least one oxygen,
C 3 -C 8 cycloalkylene, C 3 -C 10 cycloalkylalkylene,
R 3 is C1-C12 alkylene,
R 2 and R 4 are independently chosen from the side chains of L- and D-amino acids so that the carbon to which R 2 or R 4 is attached has L or D chirality;
further comprising delivering a fraction of the bacteriophages in the wound within a rapid delivery period immediately after applying the film, the rapid delivery period being smaller than 4 hours, and afterwards releasing at least part of the remaining bacteriophages in the wound at a rate smaller than within the rapid delivery period.
2. The method of claim 1 , wherein R 1 is —(CH2) 6 —, R 3 is —(CH2) 8 —, and both R 2 and R 4 are the side chain of L-leucine.
3. The method as defined in claim 1 , wherein the film further includes salt particles dispersed in the polymer.
4. The method as defined in claim 3 , wherein at least part of the bacteriophages is adsorbed on the salt particles.
5. The method as defined in claim 4 , wherein the salt particles include CaCO 3 particles.
6. The method as defined in claim 1 , wherein the film further includes a buffer.
7. The method as defined in claim 6 , wherein the buffer is TMN (Tris-MgCl 2 —NaCl) buffer.
8. The method as defined in claim 1 , wherein the film further includes at least one of silversulfadiazine, silver nitrate and nanocrystalline silver.
9. The method as defined in claim 1 , wherein the film further includes an antibiotic.
10. The method as defined in claim 1 , where the film is applied for a duration of between 1 day and 20 days.
11. The method as defined in claim 10 , wherein the film is applied for a duration of between 3 and 7 days.
12. The method as defined in claim 10 , wherein the film is a first film, the method further comprising removing the first film after the duration and applying a second film including the biodegradable polymer with the bacteriophages dispersed therein on the wound.
13. The method as defined in claim 1 , wherein the film includes an enzyme operative to degrade the film.
14. The method as defined in claim 13 , wherein the enzyme is selected from elastase and a metalloproteinase.
15. The method as defined in claim 1 , wherein the bacteriophages are present in the film at 500,000 PFU/cm 2 or more.
16. The method as defined in claim 1 , wherein the film is non-woven and non-porous.
17. The method as defined in claim 1 , wherein the film is between 100 μm and 1000 μm thick.
18. The method as defined in claim 1 , wherein the wound is a pressure ulcer.
19. The method as defined in claim 1 , wherein the wound is a burn wound.
20. The method as defined in claim 1 , wherein a bactericide is applied to the wound before the film is applied.
21. The method as defined in claim 20 , wherein the bactericide includes at least one of an antibiotic, silversulfadiazine, silver nitrate and nanocrystalline silver.
22. The method as defined in claim 1 , wherein the wound contains at least one of antibiotic-resistant and silver-resistant bacteria, the bacteriophage being specific to the at least one of antibiotic-resistant and silver-resistant bacteria.
23. The method as defined in claim 1 , wherein the film is substantially transparent when wet.
24. The method as defined in claim 1 , wherein the film is a dry solid film.
25. The method as defined in claim 1 , wherein the method is for preventing bacterial infection in the wound.
26. The method as defined in claim 1 , wherein the method is for treating bacterial infection in the wound.
27. A method of treating, reducing or preventing bacterial infection in a wound, the method comprising: applying a flexible film on the wound, the film including bacteriophages dispersed in a biodegradable polymer, wherein the polymer is selected from
(1) a poly (ester amide urea) wherein at least one diol, at least one diacid, and at least one amino acid are linked together through an ester bond, an amide bond, and a urea bond,
(2) a poly (ester urethane urea) wherein at least one diol and at least one amino acid are linked together through an ester bond, a urethane bond, and a urea bond,
(3) a poly (ester amide urethane urea) wherein at least one diol, at least one diacid, and at least one amino acid are linked together through an ester bond, an amide bond, a urethane bond, and a urea bond,
(4) a poly (ester amide urethane) wherein at least one diol, at least one diacid, and at least one amino acid are linked together through an ester bond, an amide bond, and a urethane bond,
(5) a poly (ester urea) wherein at least one diol and at least one amino acid are linked together through an ester bond and a urea bond, and
(6) a poly (ester urethane) wherein at least one diol and at least one amino acid are linked together through an ester bond and a urethane bond,
further wherein
the at least one diol is a compound of formula:
HO—R 1 —OH, R 1 is chosen from C 1 -C 12 alkylene optionally interrupted by at least one
oxygen, C 3 -C 8 cycloalkylene, C 3 -C 10 cycloalkylalkylene,
the at least one diacid is a compound of formula:
HO—(CO)—R 3 —(CO)—OH, R 3 is C 1 -C 12 alkylene,
the at least one amino acid is chosen from a naturally occurring amino acid and non-naturally occurring amino acid;
further comprising delivering a fraction of the bacteriophages in the wound within a rapid delivery period immediately after applying the film, the rapid delivery period being smaller than 4 hours, and afterwards releasing at least part of the remaining bacteriophages in the wound at a rate smaller than within the rapid delivery period.