Compound of glycosaminoglycan and its fabrication method as well as application
Inventors
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-9572832-B2
Publication Date
2017-02-21
Expiration Date
Abstract
The present invention is related to a compound conjugating a drug with a glycosaminoglycan, such as hyaluronic acid (HA), where the drug is useful for the treatment of diseases such as inflammation, auto-immune disease, allergy, infection and preferably cancer. The conjugated compound of the present invention can increase the concentration of drug at the specific site of disease by an interaction of the glycosaminoglycan used as target drug delivery carrier and the CD44 cell surface receptor, then enhancing the therapeutic efficacy and reducing the systemic side effect of the site-delivered drug.
Core Innovation
The invention relates to a covalent conjugate compound formed from hyaluronic acid and an active compound, wherein the active compound is conjugated to a carboxylic group of the hyaluronic acid, or a salt thereof, by means of a functional group to form a covalent conjugate. The covalent conjugation is direct conjugation by means of an amide bond, so that hyaluronic acid and the active compound are covalently linked through the carboxylic functionality.
The conjugated active compound is selected from Lenalidomide, Nimesulide and Celecoxib. Hyaluronic acid adheres to injured and inflamed tissues at disease sites via the CD44 receptor, thereby enabling targeted drug delivery and increasing local drug concentration to improve efficacy and reduce systemic side effects.
Covalent conjugate structures are described in which hyaluronic acid carboxyl groups are conjugated to active compounds using functional groups or linkers to form amide or ester bonds. Experimental support in the document includes fluorescence or dye accumulation and cellular uptake differences between CD44-rich and lower-CD44 cell models, enhanced cytotoxicity for HA–Lenalidomide and HA–Nimesulide versus unconjugated drugs, and improved tumor suppression in xenograft mouse models with minimal weight loss.
Claims Coverage
The independent claim covers a hyaluronic-acid/active-compound covalent conjugate where the active compound is Lenalidomide, Nimesulide, or Celecoxib and is directly conjugated to a hyaluronic-acid carboxylic group via a functional group forming a covalent amide bond. Dependent claims add quantitative and use or formulation limitations, including hyaluronic-acid average molecular-weight ranges and pharmaceutical composition and cancer-indication refinements.
Direct amide-bond covalent conjugate of hyaluronic acid and active compound
A compound consisting of a conjugate from a hyaluronic acid and an active compound, wherein the active compound is conjugated by means of a functional group to a carboxylic group of the hyaluronic acid, or a salt thereof, to form a covalent conjugate, and wherein the covalent conjugation is a direct conjugation by means of an amide bond.
Active compound selected from Lenalidomide, Nimesulide and Celecoxib
The active compound is selected from a group consisting of Lenalidomide, Nimesulide and Celecoxib.
Hyaluronic acid average molecular weight constraint
The compound is characterized by a hyaluronic acid having an average molecular weight within 10 kDa to 2000 kDa.
Treatment of colon cancer or glioblastoma
The compound is used for treating colon cancer or glioblastoma.
Pharmaceutical composition with excipients and/or diluents
A pharmaceutical composition includes at least one hyaluronic-acid conjugate of an active compound, together with one or more excipients and/or diluents.
Pharmaceutical composition for colon cancer or glioblastoma
A pharmaceutical composition as recited in claim 4 is specified for treating colon cancer or glioblastoma.
Overall, the claim set centers on directly conjugating hyaluronic acid to Lenalidomide, Nimesulide, or Celecoxib via a functional-group linkage forming a covalent amide bond, with dependent refinements specifying hyaluronic-acid molecular weight and limiting use to colon cancer or glioblastoma in both compound and pharmaceutical composition contexts.
Stated Advantages
Improves efficacy by enabling increased local drug concentration at disease sites.
Reduces systemic side effects.
Documented Applications
Treatment of colon cancer.
Treatment of glioblastoma.
Targeted drug delivery to injured and inflamed tissue at disease sites via the CD44 receptor.
Interested in licensing this patent?