Stable ascorbic acid compositions and methods of using the same
Inventors
Copeland, Dan • DURHAM, Carolyn
Assignees
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Publication Number
US-11497786-B2
Publication Date
2022-11-15
Expiration Date
Abstract
The application is directed a composition comprising organic acid (e.g., ascorbic acid), glutathione, a glutathione derivative, a glutathione conjugate, a pharmaceutically-acceptable salt thereof, or any combination thereof, and methods of using the same. In certain aspects the application is directed to glutathione, a glutathione derivative, a glutathione conjugate, a pharmaceutically-acceptable salt thereof; and an organic acid; wherein the molar ratio is about 0.5-1:1. The composition can further comprises a bicarbonate salt, wherein the molar ratio is about 0.1-0.5:0.5-1:1.
Core Innovation
The invention relates to pharmaceutical compositions comprising glutathione, a glutathione derivative, a glutathione conjugate, or a pharmaceutically-acceptable salt thereof, together with ascorbic acid and a bicarbonate, with the molar ratio of (a):(b):(c) being about 0.1–0.5:0.5–1:1. The formulation is intended to maintain the components in reduced form using formulation pH and controlled conditions to minimize oxidation.
The document further describes stability and quality concepts, including reduced fractions of oxidized glutathione and reduced versus oxidized ascorbic acid behavior after storage. It also describes storage stability examples such as up to 2–8 °C for about 72 hours and longer storage such as 4 weeks at about 5 °C.
The disclosure includes administration modalities such as inhalation therapy using particle formulations, as well as suppositories and retention enemas for rectal administration, depot preparations and implants, and oral/buccal/sublingual dosage forms. Combination therapy embodiments include corticosteroids, bronchodilators, antibiotics, and CFTR-modulating regimens including amplifiers, correctors, potentiators/modulators, and RNA modifiers.
Claims Coverage
The independent claim is directed to a specific multi-component glutathione/ascorbic acid/bicarbonate composition defined by a molar ratio, and the dependent claims further refine the composition with specific bicarbonate identity, pH and storage-related quality parameters, and specify administration by inhalation and method outcomes tied to fractional exhaled nitric oxide reduction. The independent claim contains three inventive ingredients defined together, yielding one core inventive combination and multiple claim refinements through dependents.
Glutathione with ascorbic acid and bicarbonate in defined molar ratio
A composition comprising glutathione, a glutathione derivative, a glutathione conjugate, or a pharmaceutically-acceptable salt thereof; ascorbic acid; and a bicarbonate, wherein the molar ratio of (a):(b):(c) is about 0.1–0.5:0.5–1:1.
Sodium bicarbonate as the bicarbonate component
The bicarbonate is sodium bicarbonate.
Defined pH range for the composition
The composition has a pH within one of the stated ranges, including about 5.5–10, about 5.5–8, about 6–10, or about 6–8.
Reduced glutathione fraction after storage
The reduced glutathione makes up more than about 80% to more than about 97% by weight of the total glutathione after storage for 4 weeks at about 5 °C.
Inhalation administration of the composition
The composition is administered by inhalation.
Reduction of fractional exhaled nitric oxide as an airway inflammation endpoint
A method reduces airway inflammation in a subject by administering a composition that lowers the subject’s fractional exhaled nitric oxide by at least 20%.
Claim coverage centers on a composition defined by combining glutathione (or derivative/conjugate/salt) with ascorbic acid and bicarbonate at a defined molar ratio, with refinements including sodium bicarbonate selection, specified pH ranges, and reduced glutathione fraction after storage. Further coverage ties the composition to inhalation administration and to a method outcome quantified as at least a 20% reduction in fractional exhaled nitric oxide.
Stated Advantages
Storage stability with maintenance of reduced components and minimized oxidation, including reduced fractions of oxidized glutathione and reduced versus oxidized ascorbic acid behavior after storage.
Inhibition of antibacterial/biofilm activity against clinical isolates.
Upregulation of mucociliary clearance, including reduced mucus viscosity and increased ciliary beat frequency/transport.
Reduction of airway inflammation, including inhibition of MPO activity/NETs and reduction of fractional exhaled nitric oxide (FeNO) by at least 20%.
Documented Applications
Treatment or use in chronic inflammatory lung diseases including lung transplant, cystic fibrosis, and bronchiectasis.
Use to inhibit antibacterial/biofilm activity against clinical isolates.
Use to upregulate mucociliary clearance, including effects on mucus viscosity and ciliary beat frequency/transport.
Use to reduce airway inflammation, including reducing MPO activity/NETs and lowering fractional exhaled nitric oxide (FeNO) by at least 20%.
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