Copper nanoclusters, composition comprising the same, and treatment of neurodegenerative diseases
a nano-cluster and copper nanotechnology, applied in the field of copper nanoclusters, can solve problems such as cell death or oxidative stress (os), mitochondrial dysfunction and energy failure, and inhibit the development of neurodegenerative diseases
Pending Publication Date: 2021-12-09
SHENZHEN PROFOUND VIEW PHARMA TECH CO LTD
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Benefits of technology
The use of ligand-modified CuNCs effectively reduces oxidative stress, inhibits protein aggregation, and shows neuroprotective effects, improving motor and cognitive functions in animal models of neurodegenerative diseases.
Problems solved by technology
Neurodegenerative diseases are one of the major threats to human health, characterized by progressive damage in neural cells and neuronal loss, which lead to compromised motor or cognitive function.
Due to their reactivity, high concentrations of ROS can lead to cell death or oxidative stress (OS).
The accumulation of Aβ seems to increase OS and lead to mitochondrial dysfunction and energy failure even in early stage of AD.
However, the etiology of PD is still unknown.
In terms of clinical treatment, although several drugs have been approved by the US FDA to treat mild and moderate PD, these drugs only temporarily improve the PD patient's cognitive or motor functions.
Substances with antioxidant properties such as coenzyme Q10, vitamin C, vitamin E, docosahexaenoic acid (DHA), Ginko biloba, and polyphenols have been tested but have not demonstrated legitimate evidence of any efficacy in neuroprotectivity (Liu 2017; Al Shahrani 2018).
Interestingly, despite the established connection of the role of OS in HD, trials attempting to treat the disease using classic antioxidants have largely been ineffective (Liu 2017).
However, enormous clinical data show that controlling intraocular pressure alone cannot achieve the goal of curing glaucoma.
It is because even if the control on intraocular pressure is ideal, the progressive optic nerve damage and retinal ganglion cells (RGCs) apoptosis may still get worse.
Therefore, high intraocular pressure may be only an early predisposing factor for glaucoma-related optic nerve damage, while it is difficult to prevent further loss of optic nerve function only by reducing intraocular pressure.
However, no clinical drugs have been found to effectively prevent glaucoma-related optic nerve damage currently.
For example, from this model, it has been found that ginsenoside Rg1, dexamethasone, ginkgo, and α-lipoic acid have some optic nerve protective effects, but the protective effects are not satisfactory.
Method used
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[0098](1) Synthesis of Thymine Modified Hyaluronic Acid (TMHA)
[0099]First, polyphosphate ester as a catalyst was prepared. Diethyl ether (14.5 mL) and CHCl3 (5.6 mL) were added to phosphorus pentoxide (10 g) with stirring, and the mixture was heated under reflux for 12 h at 50° C. to obtain a clear solution. After cooling down to room temperature, the solvent was distilled off under vacuum. The resultant colorless viscous residue was polyphosphate ester and used as a catalyst without further purification.
[0100]Second, the TMHA was synthesized as follows. A clear solution of thymine (23.6 mg) was obtained by dissolving in 25 mL of H2O with the addition of 0.25 mL of concentrated HCl solution (25%). Polyphosphate ester (1.5 g) was added to HA solution (50 mL, 2.2 wt %; MW120KD), followed by dropwise injection of thymine, and the mixture was heated to 50° C. for 16 h in an oil-bath and cooled down to 0° C. to precipitate unreacted thymine. Then, the supernatant solution was dialyzed fo...
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Abstract
Treatment of neurodegenerative diseases with copper nanoclusters (CuNCs), where the neurodegenerative diseases include Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), spinocerebellar ataxia (SCA), and glaucoma.
Description
FIELD OF THE INVENTION[0001]The present invention relates to the technical field of neurodegenerative diseases, particularly to copper nanoclusters (CuNCs), compositions comprising CuNCs, and their applications in treatment of neurodegenerative diseases.BACKGROUND OF THE INVENTION[0002]Neurodegenerative diseases are one of the major threats to human health, characterized by progressive damage in neural cells and neuronal loss, which lead to compromised motor or cognitive function. Common neurodegenerative diseases include Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), spinocerebellar ataxia (SCA), and glaucoma (Kim 2015; Liu 2017; Singh 2019).[0003]The pathogeneses of neurodegenerative diseases are believed to be initiated or accelerated by the oxidative stress (OS) caused by reactive oxygen species (ROS). ROS is defined as a group of reactive molecules derived from oxygen, which are generally short-lived and highl...
Claims
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IPC IPC(8): A61K47/69A61K33/34A61K47/64A61P25/28A61P25/16
CPCA61K47/6923A61K33/34B82Y5/00A61P25/28A61P25/16A61K47/64A61K31/787B82Y30/00A61K47/545A61K47/6929A61K47/61G01N33/523G01N33/5308G01N33/84B22F1/054B22F1/102A61P27/06A61K47/542A61K47/62A61K2300/00B82Y40/00C01G3/006C01P2004/04C01P2004/64C08L5/08A61K47/54A61K9/14
InventorSUN, TAOLEICHANG, BAISONG
OwnerSHENZHEN PROFOUND VIEW PHARMA TECH CO LTD