Hypertonic pharmaceutical compositions containing an anti-platinum chemoprotectant agent
Inventors
Hu, Qi-Ying • Lee, John • Shi, Fuxin
Assignees
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Publication Number
US-11857567-B2
Publication Date
2024-01-02
Expiration Date
Abstract
Hypertonic pharmaceutical compositions are disclosed. The hypertonic pharmaceutical compositions contain an anti-platinum chemoprotectant agent and a gelling agent. Also disclosed are methods of medical use of the hypertonic pharmaceutical compositions.
Core Innovation
The invention provides a hypertonic pharmaceutical composition having a calculated osmolarity of 3,000-7,000 mOsm/L, or at least 3,000 mOsm/L, and comprising 1M-2M of an anti-platinum chemoprotectant agent, a gelling agent, and an optional tonicity agent. The calculated osmolarity is calculated based on the chemoprotectant agent and the tonicity agent, if present.
The composition can include a liquid solvent, and the gelling agent is present in a quantified range relative to the solvent. The anti-platinum chemoprotectant agent is exemplified as sodium thiosulfate or a solvate thereof, and specific embodiments include hyaluronan as the gelling agent. In some claims, the composition has a pH in the range of 6.5 to 8.5 and a calculated osmolarity of 3,000-5,000 mOsm/L with 1M of the anti-platinum chemoprotectant agent and 1% (w/v) of the gelling agent relative to the liquid solvent.
The disclosed compositions are intended to prevent or mitigate platinum-induced ototoxicity, including hearing loss, by local administration to the round window. The patent further documents auditory brainstem response assessment in cisplatin-challenged models using thiosulfate-based gel formulations versus vehicle, reporting hearing protection consistent with the stated chemoprotective intent.
Claims Coverage
The document contains two independent composition claims and one independent method claim. The composition claims define hypertonic pharmaceutical compositions with calculated osmolarity, a high molarity anti-platinum chemoprotectant, a gelling agent, and an optional tonicity agent; dependent claims add pH and gelling agent concentration limitations. The method claim covers preventing or reducing platinum-induced ototoxicity by administering the composition to the round window.
Calculated hypertonic osmolarity composition with anti-platinum chemoprotectant and gelling agent
A hypertonic pharmaceutical composition having a calculated osmolarity of 3,000-7,000 mOsm/L and comprising 1M-2M of an anti-platinum chemoprotectant agent, a gelling agent, and an optional tonicity agent, wherein the calculated osmolarity is calculated based on the chemoprotectant agent and the tonicity agent, if present.
At-least-threshold calculated hypertonic osmolarity composition with anti-platinum chemoprotectant and gelling agent
A hypertonic pharmaceutical composition having a calculated osmolarity of at least 3,000 mOsm/L and comprising 1M-2M of an anti-platinum chemoprotectant agent, a gelling agent, and an optional tonicity agent; wherein the calculated osmolarity is calculated based on the chemoprotectant agent and the tonicity agent, if present.
Physicochemical constraint via pH range for the hypertonic composition
The hypertonic pharmaceutical composition has a pH in the range of 6.5 to 8.5.
Quantified gelling agent content and sodium thiosulfate anti-platinum chemoprotectant embodiment
The hypertonic pharmaceutical composition includes a liquid solvent, contains 0.8% to 2% (w/v) of the gelling agent relative to the solvent, and uses sodium thiosulfate or a solvate thereof as the anti-platinum chemoprotectant agent.
Tightened composition range for osmolarity, anti-platinum chemoprotectant, and gelling agent
A hypertonic pharmaceutical composition has a calculated osmolarity of 3,000-5,000 mOsm/L, contains 1M of the anti-platinum chemoprotectant agent, and contains 1% (w/v) of the gelling agent relative to the liquid solvent.
Round-window method to prevent or reduce platinum-induced ototoxicity
A method to prevent or reduce platinum-induced ototoxicity by administering an effective amount of a hypertonic pharmaceutical composition to the round window of a subject.
Quantified round-window dose volume range
The method is further limited such that a pharmaceutical composition dose of 50 μL to 1 mL is administered to the round window of the subject.
Overall, the claims center on hypertonic compositions defined by calculated osmolarity, 1M-2M anti-platinum chemoprotectant, and a gelling agent, with an optional tonicity agent affecting the osmolarity calculation. Dependent claims add pH and quantitative gelling agent limits, and the method claim covers round-window administration to prevent or reduce platinum-induced ototoxicity.
Stated Advantages
Prevent or mitigate platinum-induced ototoxicity (hearing loss) by local administration to the round window.
Documented Applications
Prevent or reduce platinum-induced ototoxicity by administering an effective amount of the hypertonic pharmaceutical composition to the round window of a subject.
Local intratympanic/transtympanic round-window administration for chemoprotection against platinum-induced hearing loss, evaluated using ABR testing in cisplatin challenge models.
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