Stable aqueous capsaicin injectable formulations and medical uses thereof
Inventors
Ostovic, Drazen • Musso, Gary Fred
Assignees
Ko Pharm R&d LLC • Musso And Associates LLC • Centrexion Therapeutics Corp
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Publication Number
US-11992470-B2
Publication Date
2024-05-28
Expiration Date
Abstract
The invention provides stable, aqueous capsaicin injectable formulations, a unit dose containing such injectable formulations, medical kits, and methods for using such injectable formulations and unit doses to treat patients suffering from pain, such as osteoarthritic knee pain. The stable, aqueous capsaicin injectable formulations may contain, for example, capsaicin, a solubilizing agent (e.g., a polyethylene glycol ester of a (C15-C25) hydroxyalkanoic acid), an antioxidant, and water.
Core Innovation
The disclosure relates to an aqueous capsaicin injectable formulation having a pH of 5.5 and at least 96% (w/w) water. The formulation contains capsaicin, a solubilizing agent comprising polyethylene glycol, an antioxidant, an alkali metal acetate, a chelating agent, and a tonicity modifier, and does not contain any phospholipid, polysaccharide, protein polymer, cellulose, sorbitan ester, histidine, or polyvinylpyrrolidone polymer.
The formulation is further characterized by specified concentration ranges for the capsaicin and the other formulation components. The disclosure includes exemplified aqueous trans-capsaicin injectable formulations at pH 5.5 using Kolliphor HS-15, with BHT antioxidant, EDTA chelator, and sodium acetate/citrate buffer or NaCl tonicity.
The document also characterizes stability and quality attributes, including impurity profiles, capsaicin degradation, capsaicin-dimer content limits, and particulate matter limits and particle count/size constraints after storage under defined temperature and relative humidity conditions. The formulations are framed for unit dosage form administration by injection for treating pain, with mention of medical kit arrangements and that anesthetic agents may be co-administered to attenuate initial hyperalgesia.
Claims Coverage
The claim coverage centers on an aqueous capsaicin injectable formulation with one independent claim and dependent claims that further define stability, quality, and solubilizing-system details. The independent claim includes three inventive feature groups: specified concentration ranges for capsaicin and excipients, a PEG-containing solubilizing agent, and defined water, pH, and excipient exclusion requirements.
Aqueous capsaicin injectable formulation at pH 5.5 with defined component ranges
An aqueous capsaicin injectable formulation comprising 0.04% (w/w) to 0.06% (w/w) capsaicin, 0.5% (w/w) to 1.5% (w/w) of a solubilizing agent, 0.005% (w/w) to 0.015% (w/w) of an antioxidant, 0.2% (w/w) to 1% (w/w) of an alkali metal acetate, 0.01% (w/w) to 0.05% (w/w) of a chelating agent, 0.3% (w/w) to 0.9% (w/w) of a tonicity modifier, at least 96% (w/w) water, and a pH of 5.5.
PEG-containing solubilizing agent
The solubilizing agent comprises polyethylene glycol.
Exclusion of multiple excipient classes
The formulation does not contain any phospholipid, polysaccharide, protein polymer, cellulose, sorbitan ester, histidine, or polyvinylpyrrolidone polymer.
The claims are directed to an aqueous capsaicin injectable formulation with tightly defined component ranges, a polyethylene glycol-containing solubilizing agent, at least 96% water, pH 5.5, and explicit excipient exclusions. Dependent claims further constrain capsaicin degradation, capsaicin-dimer limits, particulate matter, particle-size performance, solubilizing-system composition, polyethylene glycol identity, and osmolality.
Stated Advantages
Improved storage stability of capsaicin associated with the polyethylene glycol-based solubilizing approach.
Higher capsaicin solubilization at the desired pH using the polyethylene glycol-containing solubilizing system.
Reduced capsaicin oxidation and impurities relative to polysorbate peroxide formation.
Potential reduction of histamine release.
Documented Applications
Pain treatment by injection, including osteoarthritic knee pain and neuropathic pain.
Unit dosage form administration by injection for treating pain.
Medical kit context for an injectable formulation.
Intra-articular injection.
Intrathecal injection.
Epidural injection.
Co-administration of anesthetic agents to attenuate initial hyperalgesia.
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