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Application of sulfated fucoidan as PCSK9 inhibitor

A sulfated fucoidal oligosaccharide and sulfated technology, which is applied in the fields of application, sugar production, sugar production, etc., can solve problems such as LDL cannot be effectively removed, cost-benefit asymmetry, hypercholesterolemia, etc.

Inactive Publication Date: 2020-05-26
WEIFANG MEDICAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] Studies since 2003 have shown that proprotein convertase subtilisin / kexin type 9 (PCSK9) plays an important role in regulating cholesterol homeostasis; it can bind to low-density lipoprotein receptor (LDLR) and promote LDLR in and out of cells Degradation, so that LDL in the blood cannot be effectively cleared, resulting in hypercholesterolemia
At present, the price of PCSK9 monoclonal antibody inhibitors on the market is high, and the "cost-benefit" is extremely asymmetric, which makes it unaffordable for most patients

Method used

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  • Application of sulfated fucoidan as PCSK9 inhibitor
  • Application of sulfated fucoidan as PCSK9 inhibitor
  • Application of sulfated fucoidan as PCSK9 inhibitor

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0036] Extracting and preparing sulfated fucoidal oligosaccharides from Ascophyllum nodosum, the following steps were taken:

[0037](1) Preparation of the crude product of Ascophyllum nodosum fucoidan: wash the Ascophyllum nodosum, soak to remove salt, pulverize with a pulverizer, dry at 60°C, pulverize again, and pass through a 100-mesh sieve. Add 3 times the volume of petroleum ether to the crushed and dried Ascophyllum nodosum, and reflux at 90°C to remove most of the pigments and lipids. The filter residue was dried, ground, extracted by water extraction, heated in a water bath at 90°C for 3 hours, and centrifuged to obtain the supernatant and filter residue (repeated water extraction of the filter residue 3 times). The supernatant was collected and then concentrated to one-third of the original volume. Calculation of the volume of the concentrated solution needs to add the amount of calcium chloride to make the final concentration reach 2%. Stir while adding. At this tim...

Embodiment 2

[0054] When extracting and preparing sulfated fucoidan oligosaccharides from sea cucumbers and verifying their PCSK9-inhibiting and lipid-lowering activities, the following steps were taken:

[0055] (1) Preparation of crude sea cucumber fucoidan: Sea cucumbers were washed to remove sediment, soaked to remove salt, pulverized by a pulverizer, dried at 50°C, pulverized again, and passed through a 200-mesh sieve. Add 5 times the volume of ethyl acetate to the crushed and dried sea cucumber, and reflux at 95°C to remove most of the pigment and lipid. The filter residue is dried, ground, and extracted with papain (the mass ratio of sea cucumber extract is 1:5-1:10): add 100 mg of papain to each liter of extract, and adjust the pH value of the solution with sodium acetate and hydrochloric acid To 5.6, heat overnight in a 60°C water bath, and centrifuge to obtain the supernatant. Collect the supernatant and then concentrate it to one-third of the original volume, add 95% ethanol un...

Embodiment 3

[0066] To extract and prepare kelp sulfated fucoidan oligosaccharides, the following steps were taken:

[0067] (1) Preparation of crude kelp fucoidan: wash the kelp to remove sediment, soak to remove salt, pulverize with a pulverizer, dry at 40°C, pulverize again, and pass through a 100-mesh sieve. Add 10 times the volume of petroleum ether to the crushed and dried kelp, condense and reflux at 93°C to remove most of the pigments and lipids. The filter residue was dried, ground, extracted by water extraction, heated in a water bath at 100°C for 2 hours, and centrifuged to obtain the supernatant and filter residue (repeated water extraction of the filter residue 3 times). The supernatant was collected and then concentrated to one-third of the original volume. Calcium chloride needs to be added to calculate the volume of the concentrated solution so that the final concentration reaches 2%. Stir while adding. At this time, a white flocculent precipitate will appear, which is algi...

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Abstract

The invention discloses an application of sulfated fucoidan as a PCSK9 inhibitor. The application that the sulfated fucoidan can significantly inhibit the expression of PCSK9 protein is found for thefirst time, and a detailed embodiment is provided for the application of the sulfated fucoidan in the preparation of PCSK9 inhibitor drugs. In the embodiment of the invention, the sulfated fucoidan oligosaccharide from different sources can significantly lower the expression level of PCSK9 protein in apoE(- / -) mice, C57BL / 6 mice and cells; in the aspect of preparation, an implementation method issimple, large-scale production is easy, and a foundation is laid for conversion of the method.

Description

technical field [0001] The invention relates to the technical field of medical application of a compound, in particular to the application of a sulfated fucoidal oligosaccharide as a PSCK9 inhibitor. Background technique [0002] Cardiovascular disease is a disease with high morbidity, disability and mortality. According to the 2017 Global Human Death Causes published in 2019, cardiovascular diseases accounted for 31.8%, far ahead of other diseases such as cancer. The cardiovascular situation in my country released in 2019 is even more eye-catching. Cardiovascular diseases accounted for 40% of the diseases in 2016. Therefore, cardiovascular disease is a relatively important public health problem in the world, especially in developing countries. [0003] Hyperlipidemia is one of the main causes of atherosclerosis. When the cholesterol in the body is too high, especially the level of low-density lipoprotein (LDL-C) and triglyceride increase, the oxidized LDL or other denatu...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/7024A61P3/06C08B37/00C13K13/00
CPCA61K31/7024A61P3/06C08B37/0003C13K13/00
Inventor 郭守东杨晓倩夏彬林萍
Owner WEIFANG MEDICAL UNIV