Compositions and methods related to erythropoietin
Disclosed are methods and compositions related to the production of erythropoietin. The disclosed compositions comprise a poly amino acid. The production of erythropoietin by the disclosed compositions and methods can take place in vivo, in which the proliferation of a subject's erythropoietin-producing cells leads to an increased level of production of erythropoietin, in vitro, in which increased proliferation of cultured erythropoietin-producing cells leads to an increased production of erythropoietin, ex vivo, in which cells or tissues harvested from a subject produce erythropoietin. The disclosed compositions can be administered to a subject or applied to cells or tissues to stimulate increased production of erythropoietin. The disclosed compositions and methods can be used, for example, to treat anemia, such as anemia associated with diseases and disorders such as chronic renal failure, end stage renal disease, malignancies, HIV infections and AIDS, rheumatoid arthritis, myeloma, and myeloplastic syndrome, and other diseases and disorders.
1. A pharmaceutical composition comprising an erythropoietin production inducing peptide (EPIP), wherein the EPIP is selected from the group consisting of poly-D-glutamic acid, poly-L-glutamic acid, poly-D-aspartic acid and poly-L-aspartic acid;
erythropoietin; and
a pharmaceutically acceptable diluent, adjuvant or carrier.
2. The pharmaceutical composition of claim 1 , comprising a therapeutically effective amount each of the erythropoietin and the EPIP.
3. The pharmaceutical composition of claim 1 , comprising a therapeutically effective amount of the EPIP.
4. The pharmaceutical composition of claim 1 , wherein the erythropoietin is recombinant.
5. The pharmaceutical composition of claim 1 , wherein the EPIP is poly-D-glutamic acid.
6. The pharmaceutical composition of claim 1 , further comprising a preservative, wherein the preservative comprises benzyl alcohol, a paraben and phenol, or a mixture thereof.
7. The pharmaceutical composition of claim 1 , further comprising a buffering agent.
8. The pharmaceutical composition of claim 7 , wherein the buffering agent comprises citrate, phosphate, tartrate, succinate, adipate, maleate, lactate and acetate buffers, sodium bicarbonate, and sodium carbonate, or a mixture thereof.
9. The pharmaceutical composition of claim 1 , further comprising an isotonicity adjusting agent, wherein the isotonicity adjusting agent comprises sodium chloride, glycerol, mannitol, sorbitol, or a mixture thereof.
10. The pharmaceutical composition of claim 1 , further comprising a pH adjusting agent that adjusts the pH of the solution within the range of 5-8.
11. The pharmaceutical composition of claim 1 , further comprising human serum albumin.
12. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition is an aqueous solution, a non-aqueous suspension, or a dry powder.
13. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition is in an oral dosage form.
14. The pharmaceutical composition of claim 1 , further comprising a fatty acid, a surfactant, enteric material, or a mixture thereof.
15. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition is an in an injectable form.
16. A method for treating a condition selected from the group consisting of anemia, Crohn's Disease, ulcerative colitis, chronic renal insufficiency, end stage renal disease and wound healing, comprising:
administering a therapeutically effective amount a pharmaceutical composition comprising an erythropoietin production inducing peptide (EPIP), wherein the EPIP is selected from the group consisting of poly-D-glutamic acid, poly-L-glutamic acid, poly-D-aspartic acid and poly-L-aspartic acid;
erythropoietin; and
a pharmaceutically acceptable diluent, adjuvant or carrier, to a subject in need thereof.
17. The method of claim 16 , wherein the EPIP is poly-D-glutamic acid.
18. The method of claim 17 , wherein the administration of the poly-D-glutamic acid results in a red blood cell level of 5000 or more erythrocytes per μL of blood.
19. The method of claim 16 , wherein the method of treatment results in angiogenesis of a kidney of the subject.
20. The method of claim 16 , wherein the subject is a mammal.
21. The method of claim 16 , wherein the subject is human.
22. The method of claim 16 , wherein the pharmaceutical composition is administered by intravenous or intramuscular or subcutaneous or intraperitoneal injection.
23. The method of claim 16 , wherein pharmaceutical composition is administered orally or rectally.
24. The method of claim 16 , the pharmaceutical composition is administered by inhalant.
25. The method of claim 24 , wherein the administration by inhalant is via a spraying or droplet mechanism.