Pharmaceutical composition comprising thrombolytic peptide-tetrahydroisoquinoline conjugate
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Publication Number
US-11338008-B2
Publication Date
2022-05-24
Expiration Date
Abstract
The present invention provides a pharmaceutical composition comprising a binary conjugate, DC009, which is a conjugate of a thrombolytic peptide (Pro-Ala-Lys) and a tetrahydroisoquinoline compound having two C1-4 alkyl groups via a lysine linking arm, and a pharmaceutical acceptable carrier. The composition has a pH less than 6.5, preferably has a pH about pH 2-5.5 The composition may comprise a pharmaceutical acceptable excipient such as mannitol, sorbitol, sucrose, lactose, or trehalose.
Core Innovation
The invention relates to pharmaceutical compositions containing the thrombolytic peptide-tetrahydroisoquinoline binary conjugate DC009 (LT3001) together with a pharmaceutically acceptable carrier. The compositions are characterized by an acidic pH of less than 6.5, with a particularly described pH of about 4.5, and the composition is clear and colorless.
The compositions further include pharmaceutically acceptable excipients, with emphasis on sugar alcohols and disaccharides. The excipients are mannitol, sorbitol, sucrose, lactose, or trehalose, and the document describes formulations where DC009 and the excipient are present in defined weight ratios to support DC009 stability.
A key aspect of the invention is the demonstrated stability of DC009 under acidic conditions, including stability of formulations and lyophilized formulations after storage. The document reports that DC009 remains stable at acidic pH, that formulations with mannitol/sorbitol show improved stability versus other excipients, and that lyophilized formulations remain stable for months at elevated temperatures and can be reconstituted for intravenous use.
Claims Coverage
The independent claim contains multiple inventive elements related to a specific pharmaceutical composition profile: a compound at a specified concentration, a specified excipient concentration, an acidic pH, defined excipient selections, and a clear/colorless composition appearance. The dependent claims refine these elements primarily by specifying particular excipient/concentration combinations and a hydrochloride pharmaceutically acceptable salt.
Acidic clear and colorless DC009 pharmaceutical composition
A pharmaceutical composition having a pH of about 4.5 and being clear and colorless, comprising DC009 or a pharmaceutically acceptable salt thereof at 10 mg/mL and a pharmaceutically acceptable excipient at about 3.8% w/w or about 5% w/w.
Selected sugar alcohol or disaccharide excipient at specified w/w level
The pharmaceutically acceptable excipient is mannitol, sorbitol, sucrose, lactose, or trehalose at about 3.8% w/w or about 5% w/w in the composition having pH about 4.5.
Hydrochloride pharmaceutically acceptable salt
The pharmaceutically acceptable salt is a hydrochloride salt within the pharmaceutical composition framework.
Across the independent claim and its dependent refinements, the claim set centers on a composition containing DC009 or a pharmaceutically acceptable hydrochloride salt form at 10 mg/mL in a pharmaceutically acceptable carrier, formulated at about pH 4.5 with a clear and colorless appearance and with mannitol, sorbitol, sucrose, lactose, or trehalose excipients at about 3.8% w/w or about 5% w/w.
Stated Advantages
DC009 stability at acidic pH.
Improved DC009 stability with mannitol/sorbitol versus other excipients.
Lyophilized formulations remain stable for months at 25°C and 40°C.
Documented Applications
Reconstitution for intravenous use of lyophilized formulations.
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