Applications of pegylated curcumin derivative

A technology of pegylated curcumin and derivatives, which can be applied to medical preparations containing active ingredients, digestive systems, drug combinations, etc., can solve problems such as low oral availability, limited clinical application, and insolubility of curcumin in water.

Inactive Publication Date: 2017-04-26
THE SECOND AFFILIATED HOSPITAL OF CHONGQING MEDICAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although curcumin has definite curative effect, good safety and tolerance, 133 clinical trials have been registered on ClinicalTrials.gov, but curcumin is insoluble in water, fast in metabolism, and low in oral availability, which limits its clinical application

Method used

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  • Applications of pegylated curcumin derivative
  • Applications of pegylated curcumin derivative
  • Applications of pegylated curcumin derivative

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0031] Example 1: Synthesis and Characterization of Pegylated Curcumin Derivatives

[0032] With reference to Chinese patent CN102134312A, a brief preparation method is provided. Taking curcumin and short-chain polyoxyethylene (Mr=400~800Da) as an example, the preparation process includes the following two simple steps: (1) β-mercaptopropionic acid and curcumin Reaction generates curcumin (Curc-SH) with mercapto end; (2) Michael addition reaction occurs between curcumin with mercapto end and monomethoxypolyoxyethylene acrylate to generate the amphiphilic curcumin compound shown in I .

[0033] Specifically, taking the polyethylene glycol curcumin derivative (Curc-mPEG454) shown in structure II as an example, curcumin and two short-chain polyethylene glycol monomethyl ether acrylates are combined through a β-mercaptopropionate bond. (Mr=454Da) connected, the structure is shown as II, its synthesis method and characterization refer to patent CN102134312A and patent US2012 / 00031...

Embodiment 2

[0041] Example 2: Effects on Lipid Metabolism and Hepatic Steatosis in C57BL / 6 Mice Induced by High Fat Diet

[0042] 1. Experimental method:

[0043] Choose 8-week-old male C57BL / 6 mice, 10 per group, and randomly divide them into four groups: (1) control group (Control): normal diet D12450B+normal saline, (2) high-fat group (HFD): high-fat diet D12492+ Normal saline, (3) high-fat group+curcumin derivative low-dose treatment group (50mg / kg, Curc-mPEG454), (4) high-fat group+curcumin derivative high-dose treatment group (100mg / kg, Curc- mPEG454), intraperitoneally injecting the corresponding drug once every other day, and after 16 weeks, the HITACHI 7600 automatic biochemical analyzer detected the levels of TG, TC, HDL-C, LDL-C and FFA in the blood, alanine aminotransferase (ALT) and aspartate aminotransferase ( AST), and HE staining to observe the changes of mouse liver tissue structure and lipid deposition. The data were analyzed using SPSS17.0 software, paired t-test was ...

Embodiment 3

[0073] Example 3: To high cholesterol diet C57BL / 6 and ApoE - / - Effects on lipid metabolism and antiatherosclerotic effects in knockout mice.

[0074] 1. Experimental method:

[0075] Selection of 8-week-old male C57BL / 6 and ApoE - / - Gene knockout mice were randomly divided into five groups: (1) C57BL / 6 normal diet group + normal saline group, (2) ApoE - / - Normal diet + normal saline group, (3) ApoE - / - Normal diet + Curc-mPEG45450mg / kg group, (4) ApoE - / - High cholesterol (D12109C) + normal saline group, (5) ApoE - / - High cholesterol (D12109C)+Curc-mPEG454 50mg / kg group, 6 rats in each group, intraperitoneal injection once every other day, after 12 weeks of continuous treatment, the levels of TG, TC, HDL, LDL and FFA in serum were measured, HE and oil red O Staining was used to observe the changes in mouse liver tissue structure and lipid deposition, frozen sections of mouse aortic root, and HE staining were used to observe and measure the histological characteristics an...

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Abstract

The invention belongs to the field of pharmaceutical chemistry, and in particular relates to novel applications of pegylated curcumin derivative, especially the applications of the pegylated curcumin derivative in preparing medicines for preventing or treating fatty liver diseases and atherosclerosis. The experiment proves that the pegylated curcumin derivative can reduce the level of triglyceride in the blood, activate the phosphorylation of cyclic-AMP response element binding protein (CREB), negatively regulate nuclear transcription receptor PPAR gamma closely related to lipid metabolism, reduce the CD36 expression of the lever tissue caused by high fat diet, reduce the intake of fatty acid of the liver, reduce the lipid formation of the liver, and improve the fatty degeneration of the liver. The pegylated curcumin derivative further can improve the level of high density lipoprotein cholesterol, promote the reverse cholesterol transport, reduce the CD36 expression of macrophages, reduce the intake of oxidized low density lipoprotein, alleviate the bubblization of the macrophages, and reduce the deposition of lipid on the endangium and the formation of artery atherosclerotic plaque.

Description

technical field [0001] The invention belongs to the field of medicinal chemistry, and specifically relates to the new application of pegylated curcumin derivatives, in particular to the application of pegylated curcumin derivatives in the preparation of drugs for preventing or treating fatty liver disease and atherosclerosis . Background technique [0002] Fatty liver refers to the lesion caused by excessive accumulation of fat in liver cells caused by various reasons. Fatty liver and steatohepatitis are common in patients with excessive drinking, obesity, type Ⅱ diabetes, insulin resistance hyperlipidemia, etc. fatty liver disease (AFLD) and nonalcoholic fatty liver disease (NAFLD). Alcoholic fatty liver can be significantly improved by abstaining from alcohol, while non-alcoholic fatty liver disease refers to a clinicopathological syndrome characterized by diffuse hepatic fatty change, which is caused by alcohol and other definite liver damage factors. Progression manife...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/795A61P1/16A61P9/10A61P29/00
CPCA61K31/795
Inventor 彭明利刘玉胡鹏任红
Owner THE SECOND AFFILIATED HOSPITAL OF CHONGQING MEDICAL UNIV
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