Pharmaceutical composition for intraarticular delivery
Inventors
Hong, Keelung • Guo, Luke S. S. • TSENG, Yun-Long • Shih, Sheue-Fang • Chang, Po-Chun • Tsai, Chih-Chiang • Lin, Hong-Hui
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-11793755-B2
Publication Date
2023-10-24
Expiration Date
Abstract
The present invention provides methods of treating arthritis. A sustained release composition comprising liposomes and one or more therapeutic agent or a pharmaceutically acceptable salt thereof is administered to a subject in need thereof. The liposomes may be in an aqueous suspension. The sustained release composition can be administered intraarticularly.
Core Innovation
The invention relates to a sustained-release intraarticular arthritis treatment using aqueous liposome suspensions that include cholesterol and a defined phospholipid pair. The mixture includes a first phospholipid selected from DOPC, POPC, SPC, or EPC and a second phospholipid selected from PEG-DSPE or DOPG. Cholesterol is included at a mole percent of about 10 to about 33 based on the total amount of the first phospholipid, the second phospholipid, and cholesterol.
The disclosed approach forms or incorporates the phospholipid/cholesterol into a lipid cake, including a liposome lipid cake that may be lyophilized with cryoprotectants and buffers, and then reconstitutes the lipid cake with a therapeutic agent solution. This processing is described as yielding sustained drug release and reduced or eliminated crystal suspension compared with crystal suspensions. The therapeutic agent can include steroids, NSAIDs, DMARDs, and TNF-α antagonists.
The document describes arthritis treatment rationale and comparative performance of sustained-release liposome formulations versus free or crystal forms. The treatment is presented as enabling less frequent intraarticular dosing and longer pain relief. In vivo examples in collagen-induced arthritis rats compare free drug with sustained-release liposome compositions using arthritis scoring, body weight, and hind paw or ankle volume measures, reporting longer-lasting suppression after single or multiple intraarticular injections.
Claims Coverage
The provided independent claim recites a formulation mixture for intraarticular delivery, including defined phospholipid and cholesterol components with a specific mole-percent range. The claim set includes dependent claim refinements that further constrain component selections and quantitative ratios, and at least one dependent claim ties the mixture to an intraarticular delivery method for arthritis treatment; other dependents further specify therapeutic agent types and constrained dosing or concentration ranges.
Intraarticular delivery phospholipid/cholesterol mixture with defined mole percent
A mixture for intraarticular delivery of a therapeutic agent comprising a first phospholipid selected from DOPC, POPC, SPC, and EPC, a second phospholipid selected from PEG-DSPE or DOPG, and cholesterol at a mole percent of about 10 to about 33 based on the total amount of the first phospholipid, the second phospholipid and cholesterol.
Second phospholipid DOPG mole-percent constraint
The mixture wherein the second phospholipid is DOPG present at a mole percent ratio of about 3 to 37.5 relative to the total amounts of the first phospholipid, the second phospholipid and cholesterol.
Defined DOPC/DOPG/cholesterol mole-percent composition
A liposome composition mixture having mole-percent ratios of DOPC:DOPG:cholesterol within about 29.5–90:3–37.5:10–33.
Intraarticular administration to a subject suffering from arthritis
A method that delivers a therapeutic agent to a subject with arthritis by providing a composition containing the mixture and administering the composition intraarticularly.
Based on the provided claim content, the claim coverage centers on an intraarticular delivery liposome mixture defined by first/second phospholipid selection and a specified cholesterol mole-percent range, with further dependent constraints on DOPG content and three-component mole-percent ranges, and a method embodiment administering the composition intraarticularly to a subject with arthritis.
Stated Advantages
Enables less frequent intraarticular dosing.
Provides longer pain relief than free/crystal formulations.
Documented Applications
Treatment of arthritis using the sustained-release intraarticular liposome formulations in a collagen-induced arthritis rat model with comparisons versus free drug.
Interested in licensing this patent?