Formulations of site-specific, microparticulate compositions and their use to improve outcome after aneursymal subarachnoid hemorrhage
AssigneeEdge Therapeutics, Inc.
InventorR. Loch Macdonald
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Abstract
The described invention provides site-specific sustained release microparticulate formulations containing a therapeutic amount of an L-type voltage gated calcium channel inhibitor, a PLGA polymer comprising from 25% to 50% glycolide, and a hyaluronic acid. A therapeutic amount of the formulation is effective to reduce signs or symptoms of delayed cerebral ischemia comprising one or more of a cortical spreading ischemia, a cortical spreading depolarization, a plurality of microthromboemboli, or an angiographic vasospasm after brain injury in a mammal, while reducing the risk of systemic hypotension, cardiac dysfunction, anoxia, and intracranial hypertension.
Claims23
A site-specific microparticulate pharmaceutical formulation, comprising:
- (a) a therapeutic amount of an L-type voltage-gated calcium channel antagonist;
- (b) a poly(DL-lactide-co-glycolide) (PLGA) polymer comprising from 25% to 50% glycolide;
- and
- (c) less than 5% hyaluronic acid,
- wherein the microparticles of the formulation are characterized by:
- (i) a particle size from about 20 μm to about 125 μm;
- (ii) a drug load of from about 50% to about 70%;
- (iii) sustained release;
- and
- (iv) at least 99% purity.
A site-specific microparticulate pharmaceutical formulation for administration into an intracisternal site of administration comprising,
- (i) from 40 mg to about 1200 mg of an L-type voltage gated calcium channel antagonist;
- (ii) a poly(DL-lactide-co-glycolide) (PLGA) polymer comprising 50% glycolide;
- (iii) less than 5% of a hyaluronic acid characterized by a zero shear rate viscosity of 1677 Poise, molecular weight 1.0-2.9 million Da;
- wherein consistency of the formulation is that of a paste,
- wherein the microparticles of the formulation are characterized by:
- (a) a particle size from about 20 μm to about 125 μm;
- (b) a drug load of from about 50% to about 70%;
- (c) sustained release;
- and
- (d) at least 99% purity.
A site-specific microparticulate pharmaceutical formulation for administration into an intraventricular, intracisternal or intrathecal site of administration, comprising:
- (a) from 40 mg to 1200 mg of an L-type voltage gated calcium channel antagonist;
- (b) a poly(DL-lactide-co-glycolide) (PLGA) polymer comprising 50% glycolide;
- (c) less than 5% of a hyaluronic acid characterized by a zero shear rate viscosity of 2 Poise, molecular weight of 0.500-0.750 million Da,
- wherein viscosity of the formulation ranges from about 1.5 Poise to about 3.5 poise,
- wherein the microparticles of the formulation are characterized by:
- (i) a particle size from about 20 μm to about 125 μm;
- (ii) a drug load of from about 50% to about 70%;
- (iii) sustained release;
- and
- (iv) at least 99% purity.
Dependencies are inferred from the claim text.