Ketamine formulation for subcutaneous injection
Inventors
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Assignees
MemberBexson BiomedicalBexson BiomedicalBexson Biomedical develops precision-driven therapies for central nervous system (CNS) disorders, focusing on pain and mental health. The company is advancing a pipeline of subcutaneous drug formulations, led by an IND-ready ketamine compound for moderate/severe acute pain. Bexson also develops wearable, programmable delivery devices to enable controlled, scalable drug administration both in clinical and field settings. Their technology targets unmet needs in pain management, neuropsychiatric conditions, and military medicine.
Bexson Biomedical develops precision-driven therapies for central nervous system (CNS) disorders, focusing on pain and mental health. The company is advancing a pipeline of subcutaneous drug formulations, led by an IND-ready ketamine compound for moderate/severe acute pain. Bexson also develops wearable, programmable delivery devices to enable controlled, scalable drug administration both in clinical and field settings. Their technology targets unmet needs in pain management, neuropsychiatric conditions, and military medicine.
Publication Number
US-10973780-B2
Publication Date
2021-04-13
Expiration Date
Abstract
Provided herein are subcutaneous formulations of ketamine that are useful for treating a variety of disease and disorders. The subcutaneous ketamine formulations provided herein reduce injection site irritation and pain.
Core Innovation
The invention relates to pharmaceutical compositions comprising a compound of structural Formula (I), or an enantiomer, a mixture of enantiomers, an isotopic variant, or a pharmaceutically acceptable salt, solvate or hydrate thereof, together with at least one pharmaceutically acceptable excipient. The composition further comprises a complexing agent comprising a substituted cyclodextrin having a plurality of acidic functional groups that are deprotonated counter-anions for a protonated form of the compound of structural Formula (I), and the composition is characterized by reduced osmolality relative to a composition comprising a salt of the complexing agent and a salt of the compound of structural Formula (I).
In further embodiments, at least about 75% of the compound of structural Formula (I) is ionized and has a structure of Formula (I-A), wherein the substituted cyclodextrin comprises a plurality of acidic functional groups that are deprotonated counter-anions for a plurality of the compound of structural Formula (I-A). The patent specifically addresses complexing with sulfobutyl-ether-beta-cyclodextrin (SBE-β-CD; Captisol®/Captisol® acid).
The invention additionally covers treatment by administering a therapeutically effective amount of the pharmaceutical composition by subcutaneous or intramuscular injection. The composition has a pH from 4.5 to 7 and reduced osmolality relative to a composition comprising a salt of the complexing agent and a salt of the compound of structural Formula (I).
Claims Coverage
The independent claims cover three inventive features centered on a substituted-cyclodextrin complexing agent with deprotonated acidic functional groups and reduced osmolality relative to separate-salt controls, with additional ionization and administration limitations.
Reduced-osmolality complexed Formula (I) composition with substituted cyclodextrin counter-anions
A pharmaceutical composition comprising a compound of structural Formula (I), or an enantiomer, mixture of enantiomers, isotopic variant, or pharmaceutically acceptable salt, solvate or hydrate, at least one pharmaceutically acceptable excipient, and a substituted cyclodextrin having a plurality of acidic functional groups that are deprotonated counter-anions for a protonated form of the compound, wherein the composition has reduced osmolality relative to a composition comprising a salt of the complexing agent and a salt of the compound.
Ionized Formula (I) fraction complexed with substituted cyclodextrin deprotonated counter-anions
A pharmaceutical composition comprising a compound of structural Formula (I), or an enantiomer, mixture of enantiomers, isotopic variant, or pharmaceutically acceptable salt, solvate or hydrate, wherein at least about 75% of the compound is ionized and has a structure of Formula (I-A) associated with a substituted cyclodextrin having a plurality of acidic functional groups that are deprotonated counter-anions, wherein the pharmaceutical composition has reduced osmolality relative to a composition comprising a salt of the complexing agent and a salt of the compound.
Treating by subcutaneous or intramuscular injection of reduced-osmolality composition at pH 4.5 to 7
A method of treating a disease or disorder by administering to a subject a therapeutically effective amount of a pharmaceutical composition comprising a compound of structural Formula (I), or an enantiomer, mixture of enantiomers, isotopic variant, or pharmaceutically acceptable salt, solvate or hydrate, and a complexing agent comprising a substituted cyclodextrin having acidic functional groups that are deprotonated counter-anions for the compound, wherein the composition is administered by subcutaneous or intramuscular injection and has a pH from 4.5 to 7 and reduced osmolality relative to a composition comprising a salt of the complexing agent and a salt of the compound.
The independent claims require complexing of a compound of structural Formula (I) with a substituted cyclodextrin whose acidic functional groups act as deprotonated counter-anions for an ionized or protonated form, and they require reduced osmolality versus a separate-salt control. They further narrow embodiments by requiring at least about 75% ionization in one claim and subcutaneous or intramuscular administration with pH 4.5 to 7 in the treatment claim.
Stated Advantages
Reduced osmolality relative to a composition comprising a salt of the complexing agent and a salt of the compound of structural Formula (I).
High ionization of the compound of structural Formula (I) to the structure of Formula (I-A), at least about 75% in one independent claim.
Improved safety versus other cyclodextrins, including reduced systemic and non-target effects and considerations related to kidney toxicity and renal clearance.
Reduced local irritation, supported by formulation strategies intended to reduce injection-site injury signs.
Documented Applications
Treating a disease or disorder by administering a therapeutically effective amount of the pharmaceutical composition by subcutaneous or intramuscular injection.
Ketamine parenteral formulations used in clinical contexts relevant to ketamine efficacy and safety, including major depressive disorder (MDD) and acute post-operative pain, with referenced measurement tools such as the Hamilton Depression Rating Scale (HDRS), numeric pain rating scale (NPRS), and related biomarkers (hsCRP).
A pig skin study hypothesis comparing a Captisol® formulation versus ketamine HCl for reduced injection-site injury signs.
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