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Copper nanoclusters, thymine-modified hyaluronic acid, polycopper nanoclusters and preparation method and application of copper nanoclusters, thymine-modified hyaluronic acid and polycopper nanoclusters

A technology of thymine and hyaluronic acid, which is applied to medical preparations with non-active ingredients, medical preparations containing active ingredients, and pharmaceutical formulas, and can solve problems such as no indication of the formation of copper clusters

Active Publication Date: 2019-06-28
武汉广行科学研究有限公司
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, Yang et al. did not suggest the use

Method used

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  • Copper nanoclusters, thymine-modified hyaluronic acid, polycopper nanoclusters and preparation method and application of copper nanoclusters, thymine-modified hyaluronic acid and polycopper nanoclusters
  • Copper nanoclusters, thymine-modified hyaluronic acid, polycopper nanoclusters and preparation method and application of copper nanoclusters, thymine-modified hyaluronic acid and polycopper nanoclusters
  • Copper nanoclusters, thymine-modified hyaluronic acid, polycopper nanoclusters and preparation method and application of copper nanoclusters, thymine-modified hyaluronic acid and polycopper nanoclusters

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[0073] In some embodiments, PCuNCs synthesis method comprises:

[0074] providing a TMHA solution; in some embodiments, the TMHA solution is 0.1 mm, pH 7.0;

[0075] Add CuSO to TMHA solution 4 solution, in some embodiments, CuSO 4 The solution is 20mM, pH7.0, and added in a dropwise manner;

[0076] The mixture is thus allowed to react; in some embodiments, react at 37° C. for 20 minutes in the dark to obtain the PCuNCs solution; store the PCuNCs solution at 4° C. in the dark for use.

[0077] Under the irradiation of UV light (365 nm), the bright orange-red emission can be clearly seen, indicating that the formation of luminescent CuNCs is successful.

[0078] In some embodiments, the molar ratio between Cu and TMHA is in the range of 10:1 to 500:1, further in the range of 15:1 to 300:1, further in the range of 20:1 to 200:1 , further in the range of 25:1 to 100:1, and further in the range of 30:1 to 80:1.

[0079] PCuNCs contain well-dispersed spherical nanoclusters with...

Embodiment 1

[0093] Embodiment 1, the synthesis of thymine-modified hyaluronic acid (TMHA)

[0094] First, polyphosphate is prepared as a catalyst. Diethyl ether (14.5 mL) and CHCl 3 (5.6mL) was added into phosphorus pentoxide (10g), stirred, and heated under reflux at 50°C for 12h to obtain a clear solution. After cooling to room temperature, the solvent was distilled off under vacuum. The resulting colorless sticky residue was polyphosphate and was used as catalyst without further purification.

[0095] TMHA was synthesized as follows. dissolved in 25mL of HCl added with 0.25mL of concentrated hydrochloric acid solution (25%) 2 In O, a clear solution of thymidine (23.6 mg) was obtained. Polyphosphate (1.5g) was added to HA solution (50mL, 2.2wt%; MW120KD), then thymine was dripped, the mixture was heated to 50°C in an oil bath for 16h, and cooled to 0°C to precipitate unreacted thymine . The supernatant was then dialyzed through a dialysis bag (MWCO 8000) for 72 hours to remove an...

Embodiment 2

[0098] Example 2: Synthesis of polycopper clusters (PCuNCs) with TMHA

[0099] 10 mL of TMHA (10.5% DS) solution (0.1 mM, pH 7.0) was gradually heated to 37° C. to dissolve TMHA. 2 mL of copper sulfate (20 mM, pH 7.0) solution was added dropwise, and reacted at 37° C. for another 20 minutes in the dark. Under the irradiation of ultraviolet light (365 nm), the bright orange-red emission can be clearly seen, indicating that the formation of luminescent PCuNCs is successful. Finally, the resulting solution was stored in the dark at 4°C until use.

[0100] Cu was studied separately 2+ / TMHA molar ratio, pH value, reaction temperature, reaction time and other optimal synthesis conditions. In order to examine the Cu in the reaction system 2+ content, add 2mL CuSO of different concentrations to 10mL TMHA solution 4 , so that Cu in the reaction system 2+ The molar ratio to TMHA is 5:1, 10:1, 15:1, 20:1, 30:1, 40:1, 60:1, 80:1, 100:1. After reacting with mild stirring at 37°C an...

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Abstract

The invention provides copper nanoclusters (CuNCs), thymine-modified hyaluronic acid (TMHA), polycopper nanoclusters (PCuNCs) and a preparation method and application of CuNCs, TMHA and PCuNCs in detection, diagnosis and treatment; for example, Parkinson's disease is detected, diagnosed and treated. The TMHA is represented by formula I, wherein the degree of substitution of thymine in HA is in therange of 1-50%, and n representing the repeating number of GlcA-GlcNAc repeats is an integer from 10 to 10,000.

Description

technical field [0001] The present invention generally relates to the field of nanomedicine technology, and more specifically relates to copper clusters (CuNCs), thymine-modified hyaluronic acid (TMHA) and polycopper clusters (PCuNCs), as well as preparation methods and their use in detection , diagnosis and treatment; eg Parkinson's disease. Background technique [0002] Neurodegenerative diseases are one of the major threats to human health. Their common pathological features are abnormal tangles of proteins in nerve cells and amyloidosis, as well as related neuronal apoptosis and nerve damage. Parkinson's disease (PD) is the second most common neurodegenerative disorder characterized by tremors, muscle stiffness, bradykinesia, postural instability and movement disturbances. PD mainly occurs in the elderly, and the incidence rate increases with age. According to conservative estimates, the number of PD patients in the world has exceeded 10 million. However, the etiolog...

Claims

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Application Information

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IPC IPC(8): A61K47/69A61K33/34A61K47/64A61K47/54A61K47/60A61P25/16
CPCA61K33/24A61K47/545A61K47/542A61K47/64A61K47/54B82Y5/00A61P25/16A61K47/61
Inventor 孙涛垒常柏松
Owner 武汉广行科学研究有限公司
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