Details for Patent: 6,051,576
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Title: | Means to achieve sustained release of synergistic drugs by conjugation |
Abstract: | A codrug composition of at least two drug compounds covalently linked to one another via a labile bond to form a single codrug composition, or ionically linked to one another to form a single workings composition, and methods of use of the codrug for the treatment of various medical conditions. The codrug may be administered by itself or in the form of a bioerodible or nonbioerodible substance. |
Inventor(s): | Ashton; Paul (Boston, MA), Crooks; Peter Anthony (Lexington, KY), Cynkowski; Tadeusz (Lexington, KY), Cynkowska; Grazyna (Lexington, KY), Guo; Hone (Malden, MA) |
Assignee: | University Of Kentucky Research Foundation (Lexington, KY) |
Filing Date: | Jan 29, 1997 |
Application Number: | 08/791,071 |
Claims: | 1. A sustained release, and substantially inactive codrug, comprising at least two drugs ionically or covalently linked to one another wherein each active drug is regenerated upon bond cleavage. 2. A codrug according to claim 1, wherein said codrug comprises suramin ionically linked to amiloride. 3. A codrug according to claim 1, wherein said codrug is in injectable form. 4. A codrug according to claim 3, wherein said injectable form is selected from the group consisting of liposomes, suspensions, microsphere and nanoparticles. 5. A codrug according to claim 1, wherein said codrug is in solid form. 6. A codrug according to claim 1, wherein said codrug is applied topically. 7. A codrug according to claim 1, wherein said codrug applied topically is in a form selected from the group consisting of a transdermal patch, ointment, cream, suspension, liquid, elixir and eye drop. 8. A codrug according to claim 1, wherein said codrug is administered by a method selected from the group consisting of injection, inhalation, implantation, applied as a nasal spray, applied rectally, applied vaginally, ingested orally and applied topically. 9. A codrug according to claim 1, wherein said codrug is fixed to an implantable device. 10. A codrug according to claim 1, wherein said codrug is a coating on an implantable device. 11. A codrug according to claim 10, wherein said implantable device is or is attached to a suture. 12. A codrug according to claim 1, wherein said codrug is in the form of a nonerodible delivery vehicle. 13. A codrug according to claim 12, wherein said nonerodible delivery vehicle comprises polyvinyl alcohol. 14. A codrug according to claim 12, wherein said codrug comprises from 0.1 to up to about 100% of said nonerodible delivery vehicle. 15. A codrug according to claim 1, wherein said codrug is in the form of an erodible delivery vehicle. 16. A codrug according to claim 1, wherein said codrug comprises one molecule of suramin ionically linked to six molecules of amiloride. 17. A codrug according to claim 15, wherein said codrug comprises from 0.1 to up to about 100% of said erodible delivery vehicle. 18. A codrug according to claim 1, wherein said codrug comprises ethacrynic acid covalently linked to atenolol. 19. A codrug according to claim 1, wherein said codrug comprises 17.alpha.-21-trihydroxy-5.beta. pregnane-20-one (THS) covalently linked to form a codrug with 5FU and diethylene glycol. 20. A codrug according to claim 1, wherein said codrug comprises 17.alpha.-21-trihydroxy-5.beta. pregnane-20-one (THS) covalently linked to form a codrug with 5FU and tetraethylene glycol. 21. A codrug according to claim 1, wherein said codrug comprises prostaglandin F2 alpha (PGF2.alpha.) covalently linked to form a codrug with timolol (TM). 22. A method of inhibiting angiogenesis comprising administering an effective amount of a codrug according to claim 2 to a patient in need of angiogenesis inhibition. 23. A codrug according to claim 1, which is essentially insoluble in body fluids. 24. A codrug according to claim 1, wherein each drug is released in equimolar amounts. 25. A codrug according to claim 1, wherein at least three drugs are ionically or covalently linked to one another via an ionic bond or covalent bond. 26. A codrug according to claim 1, wherein release of the active drugs follows pseudo zero order kinetics. 27. A codrug according to claim 1, wherein the drugs are ionically linked and release of the active drugs follows pseudo zero order kinetics for about 10 days to about 6 weeks. 28. A codrug according to claim 27, wherein release of each active drug follows pseudo zero order kinetics for about 3 weeks. 29. A codrug according to claim 1, which is soluble in body fluids. 30. A composition comprising a codrug according to claim 1, and a pharmaceutically acceptable carrier. 31. A sustained release, and substantially inactive codrug, comprising at least two drugs covalently linked to one another wherein each active drug is regenerated upon bond cleavage. 32. A codrug according to claim 31, wherein said codrug is a coating on an implantable device. 33. A codrug according to claim 32, wherein said implantable device is a suture. 34. A codrug according to claim 31, wherein said codrug is in the form of a nonerodible delivery vehicle. 35. A codrug according to claim 34, wherein the nonerodible delivery vehicle comprises polyvinyl alcohol. 36. A codrug according to claim 31, wherein each drug is released in equimolar amounts. 37. A codrug according to claim 31, wherein release of each active drug follows pseudo zero order kinetics for about three weeks. |