Claims
- 1. A composition comprising: cyclodextrin complexed with artelinic acid in a 2:1 ratio.
- 2. The composition of claim 1, wherein said cyclodextrin is coordinated in a manner so as to shield the peroxide bridge of the artemisinin molecule.
- 3. The composition of claim 1, wherein said cyclodextrin is selected from the group consisting of alpha-cyclodextrin, beta-cyclodextrin and gama-cyclodextrin.
- 4. The composition of claim 1, wherein said cyclodextrin is beta-cyclodextrin selected from a group of beta-cyclodextrin analogs with similar complexing capabilities consisting of hydroxypropyl-beta-cyclodextrin, sulfobutyl ether-beta-cyclodextrin, and heptakis(2,6-di-O-methyl)-beta-cyclodextrin.
- 5. The composition of claim 1, further comprising an aqueous solution wherein said composition is dissolved in said aqueous solution.
- 6. The composition of claim 5, having a pH of 7.4.
- 7. The composition of claim 5, wherein said aqueous solution is deionized water, saline solution, or phosphate buffered saline.
- 8. A stable artemisinin formulation comprising: beta-cyclodextrin complexed with artelinic acid in a 2:1 ratio, wherein said one of said beta-cyclodextrin shields a peroxide portion of the artemisinin and a second of said beta-cyclodextrin is complexed with an aromatic benzoic acid portion of the artemisinin.
- 9. The stable artemisinin formulation of claim 8, further comprising an aqueous solution wherein said formulation is dissolved in said aqueous solution.
- 10. The stable artemisinin formulation of claim 9, having a pH of 7.4.
- 11. The stable artemisinin formulation of claim 9, wherein said aqueous solution is deionized water, saline solution, or phosphate buffered saline.
- 12. An antimalaria composition comprising: a complexed cyclodextrin formulation of artemisinin, wherein said cyclodextrin is complexed with artelinic acid in a 2:1 ratio in aqueous solution.
- 13. The antimalaria composition of claim 12, wherein said composition is stable in solution for up to 7 weeks at 40° C.
- 14. The antimalaria composition of claim 12, wherein said composition is bioavailable, membrane permeable and suitable for intravenous injection without irritability.
- 15. The antimalaria composition of claim 12, wherein said composition has a pH of about 7.4.
- 16. The antimalaria composition of claim 12, wherein said complexed cyclodextrin formulation of artemisinin remains in solution and does not precipitate with time.
- 17. The antimalaria composition of claim 12, wherein said composition is in a form of an intravenous dose, oral dose, sublingual dose, or suppository.
- 18. A method of storing the antimalarial composition of claim 12 comprising:
filtering the antimalaria composition into a vile; freeze drying the composition in said vile to form a lyophilate, wherein said lyophilate may be re-hydrated at a later date with an aqueous solution for injection.
- 19. A method of treating a patient having malaria: comprising administering to said patient the composition of claim 12.
- 20. The method of claim 19, wherein said administering is by intravenous injection.
- 21. The method of claim 19, wherein said administering is by oral dose, sublingual dose, or suppository.
- 22. The method of claim 19, wherein said administering to said patient is by a dose of 4-6 milligrams of artelinic acid per kilogram of body weight.
- 23. The method of claim 19, wherein said 40 milligrams of said artemisinin complexed with cyclodextrin is dissolved per milliliter of aqueous solution.
- 24. A method of making an artemisinin complex wherein cyclodextrin is complexed with artilinic acid in a 2:1 ratio that is stable in solution and is suitable for injection and the treatment of malaria comprising the steps of:
dissolving two moles of cyclodextrin in aqueous solution to form a first solution; sonicating said first solution to dissolve the cyclodextrin; adding one mole of artelinic acid to said first solution to form a second solution; sonicating said second solution; and incubating said second solution to form said stable artemisinin complex in solution.
- 25. The method of claim 24, wherein said incubation is conducted at 40° C. for 2-3 hours.
- 26. The method of claim 24, wherein said cyclodextrin is β-cyclodextrin.
- 27. The method of claim 24, wherein said cyclodextrin is hydroxypropyl-beta-cyclodextrin, sulfobutyl ether-beta-cyclodextrin or heptakis(2,6-di-O-methyl)-beta-cyclodextrin.
- 28. The method of claim 24, wherein if concentrations of greater than 10-15 mg of artelinic acid are used, incubation of said second solution is conducted at 40° C. overnight.
- 29. The method of claim 24, wherein said aqueous solution is selected from the group consisting of phosphate buffered saline, saline solution and deionized water.
- 30. The method of claim 24, wherein said stable artemisinin complex in solution is at a pH of 7.4.
- 31. A method of making an artemisinin complex wherein cyclodextrin is complexed with artesunic acid in a 1:1 ratio that is stable in solution and is suitable for injection and the treatment of malaria comprising the steps of:
dissolving one mole of cyclodextrin in aqueous solution to form a first solution; sonicating said first solution to dissolve the cyclodextrin; adding one mole of artesunic acid to said first solution to form a second solution; sonicating said second solution; and incubating said second solution to form said stable artemisinin complex in solution.
- 32. The method of claim 31, wherein said incubation is conducted at 40° C. for 2-3 hours.
- 33. The method of claim 31, wherein said cyclodextrin is β-cyclodextrin.
- 34. The method of claim 31, wherein said cyclodextrin is hydroxypropyl-beta-cyclodextrin, sulfobutyl ether-beta-cyclodextrin or heptakis(2,6-di-O-methyl)-beta-cyclodextrin.
- 35. The method of claim 31, wherein if concentrations of greater than 10-15 mg of artesunic acid are used, incubation of said second solution is conducted at 40° C. overnight.
- 36. The method of claim 31, wherein said aqueous solution is selected from the group consisting of phosphate buffered saline, saline solution and deionized water.
- 37. The method of claim 31, wherein said stable artemisinin complex in solution is at a pH of 7.4.
- 38. A method of changing the physiochemical properties of artemisinin rendering it stable in solution, bioavailable, membrane permeable and non-inflammatory comprising:
adding cyclodextrin to artelinic acid under conditions to form a 2:1 complex wherein a peroxide portion of an artelinate backbone from the artelinic acid is shielded from hydrolytic decomposition by a cyclodextrin and an aromatic benzoic acid portion of the artelinate is complexed with a second cyclodextrin.
- 39. An antimalarial composition comprising:
a complexed cyclodextrin formulation of artemisinin, wherein said cyclodextrin is complexed with artesunic acid in a 1:1 ratio in an aqueous solution.
- 40. A method of storing the antimalarial composition of claim 39 comprising:
filtering the antimalaria composition into a vile; freeze drying the composition in said vial to form a lyophilate, wherein said lyophilate may be re-hydrated at a later date with an aqueous solution for injection.
- 41. The antimalarial composition of claim 39, wherein said composition is stable in solution for up to 7 weeks at 40° C.
- 42. The antimalarial composition of claim 39, wherein said composition is bioavailable, membrane permeable and suitable for intravenous injection without irritability.
- 43. The antimalarial composition of claim 39, wherein said composition has a pH of about 7.4.
- 44. The antimalarial composition of claim 39, wherein said complexed cyclodextrin formulation of artemisinin remains in solution and does not precipitate with time.
- 45. The antimalarial composition of claim 39, wherein said composition is in a form of an intravenous dose, oral dose, sublingual dose, or suppository.
- 46. A method of treating a patient with malaria: comprising administering to said patient the composition of claim 39.
- 47. The method of claim 39, wherein said administering is by intravenous injection.
- 48. The method of claim 39, wherein said administering is by oral dose, sublingual dose, or suppository.
- 49. The method of claim 39, wherein said administering to said patient is by a dose of 4-6 milligrams of artesunic acid per kilogram of body weight.
- 50. The method of claim 39, wherein said 40 milligrams of said artemisinin complexed with cyclodextrin is dissolved per milliliter of aqueous solution.
- 51. A composition comprising: cyclodextrin complexed with artesunic acid in a 1:1 ratio.
- 52. The antimalaria composition of claim 51, wherein said cyclodextrin is selected from the group consisting of alpha-cyclodextrin, beta-cyclodextrin and gama-cyclodextrin.
- 53. The composition of claim 51, wherein said cyclodextrin is beta-cyclodextrin selected from a group of beta-cyclodextrin analogs with similar complexing capabilities consisting of hydroxypropyl-beta-cyclodextrin, sulfobutyl ether-beta-cyclodextrin, heptakis(2,6-di-O-methyl)-beta-cyclodextrin, to name a few.
- 54. The composition of claim 51, further comprising an aqueous solution wherein said composition is dissolved in said aqueous solution and is stable in said aqueous solution.
- 55. The composition of claim 54, having a pH of 7.4.
- 56. The composition of claim 54, wherein said aqueous solution is deionized water, saline solution, or phosphate buffered saline.
- 57. A stable artemisinin formulation comprising: beta-cyclodextrin complexed with artesunic acid in a 1:1 ratio, wherein said beta-cyclodextrin shields a peroxide portion of the artemisinin.
Parent Case Info
[0001] This application claims priority of provisional application No. 60/362,985 filed Mar. 7, 2002.
GOVERNMENT INTEREST
[0002] The invention described herein may be manufactured, used and licensed by or for the U.S. Government.
Provisional Applications (1)
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Number |
Date |
Country |
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60362985 |
Mar 2002 |
US |