Hyaluronan conjugates and uses thereof
Inventors
LEE, Szu-Yuan • LAI, Ping-Shan • Lin, Chih-An
Assignees
National Chung Hsing University • Holy Stone Healthcare Co Ltd • Aihol Corp
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Publication Number
US-11524079-B2
Publication Date
2022-12-13
Expiration Date
Abstract
Disclosed herein is a hyaluronan conjugate, which includes a hyaluronic acid (HA), a sex hormone, and a linker for coupling one of the disaccharide units of the HA and the sex hormone. Also disclosed herein are the uses of the hyaluronan conjugate in treating or preventing neurodegenerative diseases.
Core Innovation
The invention relates to HA–sex hormone conjugates in which hyaluronic acid (HA) or a salt thereof is covalently coupled to a selected sex hormone using a linker. The sex hormone is selected from estrone, estradiol, estriol, testosterone, and 11-deoxycorticosterone, and the linker couples the sex hormone with one of the disaccharide units of the HA or salt thereof.
The linker is selected from one or more β-alanine, lipid, dihydrazide-C2-C20 dicarboxylic acid, and C2-C20 dicarboxylic acids, with coupling to a hormone hydroxyl group —OH. The conjugates are defined with properties including a degree of substitution (DS) for HA in the range of 0.1–60% and a weight-average molecular weight (Mw) for HA of about 5–500 kDa.
Representative HA–sex hormone–linker embodiments include estrone/estradiol with succinate or ADH-succinate, and β-alanine/β-alanine-succinate variants. A central purpose described in the document is the therapeutic use of the HA–sex hormone conjugates for neurodegenerative diseases, and the document states that an unexpected discovery provides therapeutic benefit while reducing sex-hormone side effects on other organs.
Claims Coverage
The independent claim covers a hyaluronan conjugate defined by three core elements: HA (or salt), a selected sex hormone from a defined group, and a covalent linker that couples the hormone to one of the HA disaccharide units, with the linker restricted to specified linker classes. The main inventive features are set out as separate claim-defined elements, with dependent claims further refining conjugate properties and extending to a pharmaceutical composition for neurodegenerative diseases using an effective amount and pharmaceutically acceptable excipient.
Hyaluronic acid (HA) (or salt) as the hyaluronan component
A hyaluronic acid (HA) or salt thereof as part of a hyaluronan conjugate, with coupling to one of the disaccharide units of the HA or salt thereof.
Selected sex hormone covalently coupled to HA
A sex hormone selected from estrone, estradiol, estriol, testosterone, and 11-deoxycorticosterone, covalently coupled to the HA (or salt thereof) through a linker.
Linker selected from β-alanine, lipid, dihydrazide-C2-C20 dicarboxylic acid, and C2-C20 dicarboxylic acids
A linker covalently coupling the sex hormone with one of the disaccharide units of the HA or salt thereof, wherein the linker is selected from β-alanine, lipid, dihydrazide-C2-C20 dicarboxylic acid, and C2-C20 dicarboxylic acids.
Overall, claim coverage is directed to a conjugate architecture (HA or salt + defined sex hormone + covalent linker restricted to specified linker classes), with dependent claims refining HA substitution and molecular-weight ranges, specifying coupling to the hormone hydroxyl group (—OH), and selecting particular linker embodiments, and at least one dependent claim extending to a pharmaceutical composition treating enumerated neurodegenerative diseases.
Stated Advantages
Provides an unexpected discovery of therapeutic benefit.
Reduces sex-hormone side effects on other organs.
Documented Applications
A pharmaceutical composition for treating neurodegenerative diseases, including Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), Huntington’s disease (HD), frontotemporal dementia, epilepsy, neuropathic pain, and ataxia.
Reduction of risk for neurodegenerative disease, as stated in the disclosure.
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