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A Method for Mitigating Osteoporosis Using Metallic Gold Cluster Molecules

a cluster molecule and metal technology, applied in the direction of heavy metal active ingredients, drug compositions, pharmaceutical delivery mechanisms, etc., can solve the problems of osteoclast overabundance, affecting the effectiveness of osteoclasts, and more fragile bone structur

Active Publication Date: 2018-07-26
GAO XUEYUN
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The gold-peptide cluster molecules effectively inhibit osteoclast formation and bone resorption, as demonstrated by reduced TRAP-positive staining, F-actin ring formation, and bone lamella resorption, with no cytotoxicity up to 500 μM concentrations, showing promise in improving bone density and preventing osteoporosis.

Problems solved by technology

This syndrome eventually leads to a more fragile bone structure.
For example, genetic factors that can lead to reduced estrogen or prostaglandin are possible causes of osteoclast over-abundance.
However, the size of gold particles was found to affect its effectiveness.
However, pure gold nanoparticles are not stable and are prone to aggregate into large colloidal gold particles which are not biologically active.

Method used

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  • A Method for Mitigating Osteoporosis Using Metallic Gold Cluster Molecules
  • A Method for Mitigating Osteoporosis Using Metallic Gold Cluster Molecules
  • A Method for Mitigating Osteoporosis Using Metallic Gold Cluster Molecules

Examples

Experimental program
Comparison scheme
Effect test

example 1

[0050]For clarity reasons, the example in this application was conducted using a published peptide sequence (SEQ ID NO:1) Cys-Cys-Tyr-Gly-Gly-Pro-Lys-Lys-Lys-Arg-Lys-Pro-Gly. See Liu, R., et al, “The Au Clusters Induce Tumor Cell Apoptosis via Specifically Targeting Thioredoxin Reductase 1 (TrxR1) and Suppressing Its Activity”, Chem. Commun., 2014, 50, 10687-10690. The chemical reaction is as the following:

Peptide-TyrOH+OH−+HAuCl4→Peptide-Tyr=O+Au25(peptide)9  (I)

[0051]All chemicals were purchased from Sigma-Aldrich, unless otherwise indicated. Ultrapure water was used throughout the experiments. The peptides with 95% purity were chemically synthesized by a solid phase method (China Peptides Co. Ltd.). All glassware were washed with aqua regia, and then rinsed with ultrapure water and ethanol. An aqueous solution of HAuCl4 (25 mM, 80 μL) was slowly added to peptide solution (1.06 mM, 1880 μL) in a 5 mL vial under vigorous stirring at room temperature, then NaOH (0.5 M, 40 μL) was ad...

example 2

[0053]Another metallic gold-peptide cluster complex sample was made by using peptide (SEQ ID NO: 2) Glu-Cys-Gly (GSH) with the published procedure similar to the procedure in EXAMPLE 1 with the chemical reaction (II). See Luo, Z., et al, “From Aggregation-Induced Emission of Au(I)-Thiolate Complexes to Ultra bright Au(0)@Au(I)-Thiolate Core-Shell Clusters”, J. Am. Chem. Soc., 2012, 134, 16662-16670.

GSH+OH−+HAuCl4→Au25(SG)18+GS-SG  (II)

[0054]FIG. 3C is the mass spectrometry of the generated gold-peptide cluster molecules showing a molecule formula of Au25(SG)18. FIGS. 3A and 3B show the absorbance and fluorescence emission spectra of the gold Au25(SG)18 cluster molecules. The absorbance and the maximum fluorescence emission peaks are located at 294 nm and 607 nm, respectively.

example 3

[0055]Another metallic gold-peptide cluster complex sample is made by using human serum album protein (HSA) with the following chemical reaction:

HSA-TyrOH+OH−+HAuCl4→HSA-Tyr=O+HSA-Au4000  (III)

[0056]All chemicals were purchased from Sigma-Aldrich, unless otherwise indicated. Ultrapure water was used throughout the experiments. All glassware were washed with aqua regia, and then rinsed with ultrapure water and ethanol. Aqueous HAuCl4 solution (5 mL, 10 mM, 37° C.) was added to HAS solution (5 mL, 5 mg / mL, 37° C.) under vigorous stirring. Two minutes later, NaOH solution (0.5 mL, 1 M) was introduced and the reaction was allowed to proceed under vigorous stirring at 37° C. for 12 hours. After the reaction, the sample was concentrated by a dialysis tube (MWCO: 100 kDa) to remove un-reacted free HSA, NaOH and HAuCl4. The obtained HSA-bound AuCs are suspended in the water and kept in dark at 4° C. UV-VIS spectrum (FIG. 4) of HSA-bound metallic gold cluster molecules shows the characterist...

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Abstract

A therapeutic method for mitigating bone loss. This method includes preparing and administering to animals intraperitoneally or orally a therapeutic agent containing metallic gold cluster molecules as an active ingredient.

Description

CROSS-REFERENCE[0001]Priority is claimed from the US Provisional Patent Application No. 62 / 448,700, filed on Jan. 20, 2017, entitled “Method for Mitigating Osteoporosis With Gold Nano-particles,” the entirety of which is hereby incorporated by reference for all purposes.DESCRIPTION OF RELATED ART[0002]The present application relates to osteoporosis treatment and more particularly to a method of using metallic Au(0)-peptide cluster molecules as agents in mitigation of bone loss in animals.[0003]Note that the points discussed below may reflect the hindsight gained from the disclosed inventions, and are not necessarily admitted to be prior art.[0004]Osteoporosis is a detrimental disease that affects 54 million Americans today with about 1 in 2 women and 1 in 4 men who will be affected by the time they reach the age of 50. Osteoporosis is caused by the lack of bone formation or from too much bone decomposition. This syndrome eventually leads to a more fragile bone structure. People suff...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K47/64A61K9/00A61K33/24A61K33/242A61K33/244
CPCA61K47/643A61K33/24A61K9/0053A61K33/244A61K33/242A61K47/64A61K9/0019A61P19/10
Inventor GAO, XUEYUN
Owner GAO XUEYUN