Stabilized nanoparticle formulations of camptotheca derivatives
First Claim
1. A pharmaceutical formulation comprising:
- a camptothecin analog;
a stabilizing agent that stabilizes the camptothecin analog but does not covalently bind thereto;
an optional targeting ligand; and
an optional excipient.
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Abstract
Pharmaceutical formulations are provided that increase the systemic bioavailability of camptotheca derivatives; preferably, the camptothecin derivative is 7-ethyl-10-hydroxyl camptothecin, SN-38. The drug is complexed with a stabilizing agent, but is not covalently bound thereto. Anionic or neutral lipids and/or polymers are used as the stabilizing agent, and secondary stabilizing agents and/or other excipients may be incorporated into the formulation as well. Therapeutic methods are also provided, wherein a formulation of the invention is administered to a patient to treat a condition, disorder, or disease that is responsive to camptothecin derivatives. Generally, administration is oral or parenteral.
146 Citations
67 Claims
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1. A pharmaceutical formulation comprising:
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a camptothecin analog;
a stabilizing agent that stabilizes the camptothecin analog but does not covalently bind thereto;
an optional targeting ligand; and
an optional excipient. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 62, 63, 64, 65)
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53. A method for making a nanoparticulate formulation of a camptothecin analog, comprising:
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(a) admixing, in a solvent, a camptothecin analog and a stabilizing agent that stabilizes the camptothecin analog but does not covalently bond thereto;
(b) removing the solvent in a manner effective to provide a dry formulation of the camptothecin analog; and
(c) rehydrating the dry formulation to provide the nanoparticulate formulation. - View Dependent Claims (54, 55, 56, 57, 58, 59, 60, 61)
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66. A method for treating an individual suffering from cancer, comprising administering to the individual a spatially stabilized matrix formulation of:
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(a) drug-containing particles comprised of (i) a stabilizing agent, (ii) a camptothecin analog that is entrapped by but not covalently bound to the stabilizing agent, optionally (iii) a targeting ligand, and optionally (iv) an excipient selected from the group consisting of saccharides, liquid polyethylene glycols, propylene glycol, glycerol, ethyl alcohol, and combinations thereof, in (b) an aqueous vehicle suitable for parenteral drug administration. - View Dependent Claims (67)
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Specification