Rifabutin treatment methods, uses, and compositions
Inventors
Lociuro, Sergio • Biondi, Stefano • Dale, Glenn E. • BOUROTTE, Marilyne • Gitzinger, Marc
Assignees
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Publication Number
US-11344537-B2
Publication Date
2022-05-31
Expiration Date
Abstract
The invention provides formulations containing highly concentrated solutions of rifabutin and methods of making such formulations. The invention also provides methods of using such formulations to treat a bacterial infection in a subject.
Core Innovation
The invention relates to rifabutin formulations produced from rifabutin powder in the presence of an acid, water, and a solvent suitable to promote dissolution of the rifabutin. The formulations are based on creating and using combinations of acid, water, and solvent so that rifabutin powder dissolves to form the rifabutin-containing formulation.
The described formulations and preparation schemes define solution components as a solvent, water, and an acid, and then add the solution to rifabutin powder to cause dissolution, or alternatively add a water-and-acid solution to a rifabutin solution in a solvent to produce an aqueous rifabutin formulation. The solvent and acid components are selected from specified options, including solvent choices such as DMI and transcutol HP, and acid choices such as acetic acid and D-glucuronic acid.
The disclosed subject matter further associates these rifabutin formulations with treating bacterial infections by administering a therapeutically effective amount of rifabutin in an injectable formulation or by inhalation. The document description links the ability to achieve highly concentrated rifabutin solutions suitable for non-oral routes with efficacy and prevention of resistance, including discussion of pharmacokinetics measures such as AUC/MIC and Cmax/MIC.
Claims Coverage
The independent claims cover four main areas: (i) a rifabutin formulation produced from rifabutin powder using acid, water, and a dissolution-promoting solvent; (ii) a method preparing such a formulation by adding a solvent/water/acid solution to rifabutin powder; (iii) a method preparing an aqueous rifabutin formulation by adding a water-and-acid solution to a rifabutin solution in a solvent; and (iv) a treatment method using an injectable formulation or inhalation.
Rifabutin formulation produced from rifabutin powder with acid, water, and dissolution-promoting solvent
A rifabutin formulation produced from a rifabutin powder in the presence of an acid, water, and a solvent suitable to promote dissolution of the rifabutin.
Preparing a formulation by adding solvent-water-acid solution to rifabutin powder
A method comprising preparing a solution comprising a solvent, water and an acid; and adding said solution to rifabutin powder, thereby causing the rifabutin to dissolve in the solution.
Preparing an aqueous formulation by adding water-and-acid solution to a rifabutin-in-solvent solution
A method comprising preparing a solution comprising water and an acid; and adding said solution to a rifabutin solution in a solvent, thereby producing an aqueous rifabutin formulation.
Treating bacterial infection by administering injectable formulation or inhalation
A method of treating a bacterial infection in a subject comprising administering a therapeutically effective amount of rifabutin in an injectable formulation or by inhalation.
Across the independent claims, the core inventive concept is forming rifabutin formulations by combining rifabutin powder (or rifabutin in solvent) with an acid and water using a dissolution-promoting solvent, and then using those rifabutin formulations for treating bacterial infections via injectable administration or inhalation.
Stated Advantages
Enable highly concentrated rifabutin solutions for non-oral (intravenous and inhaled) administration routes.
Achieve improved local/free rifabutin concentrations linked to efficacy and resistance prevention.
Documented solubility and dissolution performance via experimental solubility screening and reported dissolution/precipitation behavior upon dilution, including impurity profiling and stability after storage and terminal sterilization.
Documented Applications
Treating bacterial infections in a subject by administering rifabutin in an injectable formulation or by inhalation.
Non-oral treatment contexts referenced in the document description include intravenous (IV) administration and inhalation (IN) for bacterial infections, including examples of organisms such as A. baumannii and M. tuberculosis.
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