Oral DTPA for radionuclide chelation
AssigneeSRI International
InventorsGita Natarajan Shankar, Helen Jaber Parish
Life of this patent
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Abstract
A composition for oral radionuclide chelation therapy comprises a DTPA chelate selected from Zn-DTPA and Ca-DTPA and a permeation enhancer that preferentially increases jejunal uptake of the DTPA chelate. The composition has a DTPA chelate bioavailability of at least 10% of the chelate when orally administered to a mammal.
Claims29
A composition for oral radionuclide chelation therapy, said composition consisting of:
- a DTPA (diethylenetriaminepentaacetate) chelate selected from the group consisting of calcium-DTPA (Ca-DTPA) and zinc-DTPA (Zn-DTPA);
- a permeation enhancer that preferentially increases jejunal uptake of the DTPA chelate;
- and
- one or more excipients or binders to facilitate formulation;
- wherein the permeation enhancer is caprylocaproyl macrogol-8-glycerides, and the composition has a DTPA chelate bioavailability of at least 10% when orally administered to a mammal, as measured in a Beagle dog model and using the calculation:
- BA=AUCPO×Doseiv /AUCiv×DosePO;
- where BA=bioavailability, and AUC=area under plasma concentration-time curve, and said composition is (a) in an enteric-coated unit dosage form, or (b) in the form of extruded beads contained within a capsule, wherein the beads have an average diameter between 0.1-1 mm.
A composition for oral radionuclide chelation therapy, said composition consisting of:
- a DTPA (diethylenetriaminepentaacetate) chelate selected from the group consisting of calcium-DTPA (Ca-DTPA) and zinc-DTPA (Zn-DTPA);
- a permeation enhancer that preferentially increases jejunal uptake of the DTPA chelate;
- a P glycprotein (Pgp) inhibitor;
- and
- one or more excipients or binders to facilitate formulation;
- wherein the permeation enhancer is caprylocaproyl macrogol-8-glycerides, the Pgp inhibitor is d-α-tocopheryl polyethylene glycol 1000 succinate, and the composition has a DTPA chelate bioavailability of at least 10% when orally administered to a mammal, as measured in a Beagle dog model and using the calculation:
- BA =AUCPO×Doseiv/AUCiv×DosePO;
- where BA =bioavailability, and AUC =area under plasma concentration-time curve, and said composition is (a) in an enteric-coated unit dosage form, or (b) in the form of extruded beads contained within a capsule, wherein the beads have an average diameter between 0.1-1 mm.
A composition for oral radionuclide chelation therapy, said composition consisting of:
- a DTPA (diethylenetriaminepentaacetate) chelate selected from the group consisting of calcium-DTPA (Ca-DTPA) and zinc-DTPA (Zn-DTPA);
- a permeation enhancer that preferentially increases jejunal uptake of the DTPA chelate;
- and
- one or more excipients or binders to facilitate formulation;
- wherein the permeation enhancer is caprylocaproyl macrogol-8-glycerides, and said composition is (a) in an enteric-coated unit dosage form, or (b) in the form of extruded beads contained within a capsule, wherein the beads have an average diameter between 0.1-1 mm.
A composition for oral radionuclide chelation therapy, said composition consisting of:
- a DTPA (diethylenetriaminepentaacetate) chelate selected from the group consisting of calcium-DTPA (Ca-DTPA) and zinc-DTPA (Zn-DTPA);
- a permeation enhancer that preferentially increases jejunal uptake of the DTPA chelate;
- a P glycprotein (Pgp) inhibitor;
- and
- one or more excipients or binders to facilitate formulation;
- wherein the permeation enhancer is caprylocaproyl macrogol-8-glycerides, the Pgp inhibitor is d-α-tocopheryl polyethylene glycol 1000 succinate, and said composition is (a) in an enteric-coated unit dosage form, or (b) in the form of extruded beads contained within a capsule, wherein the beads have an average diameter between 0.1-1 mm.
Dependencies are inferred from the claim text.