Carbon-substituted diketopiperazine delivery systems
View Patent ↗Compositions useful in the delivery of active agents are provided. These delivery compositions include (a) an active agent; and (b) a carrier of at least one mono-C-substituted or di-C-substituted diketopiperazine. Methods for preparing these compositions and administering these compositions are also provided.
1. A composition comprising
(a) a biologically active agent; and
(b) at least one diketopiperazine having the formula:
wherein
R and R 1 are C 1 -C 24 alkyl having a functional group selected from halogen, oxygen, sulfur or nitrogen;
R and R 1 optionally interrupted with O, N, or S;
R and R 1 are optionally substituted with C 1 -C 4 alkyl, C 1 -C 4 alkenyl or CO 2 R 2 or any combination thereof; and
R 2 is hydrogen, C 1 -C 4 alkyl, or C 1 -C 4 alkenyl.
2. The composition as defined in claim 1 , further comprising a microsphere.
3. The composition as defined in claim 2 , wherein said microsphere comprises a microcapsule.
4. The composition as defined in claim 2 , wherein said microsphere has a diameter of less than about 10 μm.
5. The composition as defined in claim 1 , wherein said biologically active agent is selected from the group consisting of human growth hormone, bovine growth hormone, growth hormone-releasing hormone, an interferon, interleukin-I, interleukin-II, insulin, heparin, calcitonin, erythropoietin, atrial naturetic factor, a monoclonal antibody, somatostatin, adrenocorticotropin, gonadotropin releasing hormone, oxytocin, vasopressin, vancomycin, or any combination of any of the foregoing.
6. The composition as defined in claim 1 , wherein said biologically active agent is selected from the group consisting of an interferon, interleukin-I, interleukin-II, insulin, heparin, calcitonin, oxytocin, vasopressin, vancomycin, or any combination of any of the foregoing.
7. The composition as defined in claim 1 , wherein said diketopiperazine is derived from lysine.
8. The composition as defined in claim 1 , wherein R and R 1 are substituted with CO 2 R 2 and R 2 is H.
9. The composition as defined in claim 1 , wherein Rand R 1 are substituted with a C 1 -C 4 alkenyl group.
10. The composition as defined in claim 8 , wherein R and R 1 are substituted with a C 1 -C 4 alkenyl group.
11. The composition as defined in claim 1 , wherein R and R 1 are interrupted by nitrogen.
12. The composition as defined in claim 8 , wherein R and R 1 are interrupted by nitrogen.
13. The composition as defined in claim 1 , wherein the functional group is oxygen.
14. The composition as defined in any of claims 1 - 4 or 7 - 13 , wherein the biologically active agent is insulin.
15. A method of administering insulin to a subject in need thereof comprising administering to the subject the composition of claim 14 .