Method for treating and preventing atherosclerosis and complications thereof

a technology for atherosclerosis and complications, applied in the field of atherosclerosis and complications thereof, can solve the problems of obesity, obesity syndrome, increased fat synthesis, etc., and achieve the effect of increasing the risk of vascular events

Inactive Publication Date: 2019-11-21
TALENGEN INTERNATIONAL LIMITED
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0033]In another aspect, the present invention relates to: Item 13. A method for preventing atherosclerosis, comprising administering plasminogen to a subject to prevent atherosclerosis in one or more ways selected from: promoting fat metabolism in the liver, promoting fat transport in the liver, and reducing fat deposition in the liver of the subject.
[0149]The plasminogen of the present invention for in vivo administration must be sterile. This can be easily achieved by filtration through a sterile filtration membrane before or after freeze drying and reconstitution.

Problems solved by technology

Lipid metabolism disorders can also result in occurrence of obesity (obesity syndrome).
(2) Insulin secretion is increased, e.g., hyperinsulinemia is caused by excessive insulin injection in a patient with early non-insulin-dependent diabetes mellitus, and islet B cell tumor secretes excessive insulin, both of which increases fat synthesis, thereby causing obesity.
Hypolipidemic drugs can also result in fatty liver by interfering with lipoprotein metabolism.
One of the hazards of fatty liver is that it promotes the formation of atherosclerosis.
One of the causes of atherosclerosis is that a patient with fatty liver is often accompanied by hyperlipemia, and thus blood viscosity is increased, wherein low-density lipoprotein (LDL) can easily penetrate an arterial intima and deposit on a vascular wall due to its extremely small molecular weight, which reduces the arterial elasticity, narrows the vascular diameter, weakens the flexibility, and finally leads to the disturbance of blood circulation.
The second hazard of fatty liver is to induce or aggravate hypertension, and coronary heart disease, and easily lead to myocardial infarction and thus sudden death.
The fourth hazard of fatty liver is to lead to hepatic cirrhosis, liver failure, and liver cancer.
The lipid droplets in the hepatocytes are increased, resulting in steatosis and enlargement of the hepatocytes, and extrusion of the nuclei away from the center.
Fat accumulation in hepatocytes further aggravates the burden of mitochondria and endoplasmic reticulum and reduces their functions, thus affecting the metabolism of other nutrients, hormones and vitamins.
The disease occurs mostly in the last three months of pregnancy, and its clinical manifestations are often similar to acute severe liver disease, and comprise acute liver failure, pancreatitis, renal failure, and systemic coagulation abnormality, leading to rapid death.
If the concentration of blood glucose in a patient with obesity-induced fatty liver exceeds the normal level, generally pre-diabetes mellitus is considered true although this situation does not meet the diagnostic criteria of diabetes mellitus.
Fatty liver and diabetes mellitus often accompany each other and interact with each other, which brings greater difficulties to clinical treatment.

Method used

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  • Method for treating and preventing atherosclerosis and complications thereof
  • Method for treating and preventing atherosclerosis and complications thereof
  • Method for treating and preventing atherosclerosis and complications thereof

Examples

Experimental program
Comparison scheme
Effect test

example 1

Plasminogen Lowers Risk of Atherosclerosis Formation in 3% Cholesterol Hyperlipemia Model Mice

[0183]Sixteen 9-week-old male C57 mice were fed with a 3% cholesterol high-fat diet (Nantong TROPHIC) for 4 weeks to induce hyperlipemia[30,31]. This model was designated as the 3% cholesterol hyperlipemia model. The model mice continued to be fed with a 3% cholesterol high-fat diet. 50 μL of blood was taken from each mouse three days before administration, and the total cholesterol (T-CHO) was detected. The mice were randomly divided into two groups based on the total cholesterol concentration and the body weight, 8 mice in each group. The first day of administration was recorded as Day 1. Mice in the group administered with plasminogen were injected with human plasminogen at a dose of 1 mg / 0.1 mL / mouse / day via the tail vein, and an equal volume of PBS was administered to mice in the control group administered with vehicle PBS via the tail vein. After administration on Day 20, the mice beg...

example 2

Plasminogen Lowers the Content of Serum Total Cholesterol in ApoE Atherosclerosis Mice

[0186]Thirteen 6-week-old male ApoE mice were fed with a high-fat and high-cholesterol diet (Nantong TROPHIC, TP2031) for 16 weeks to induce the hyperlipemia model[40, 41]. The model mice continued to be fed with a high-fat and high-cholesterol diet. 50 μL of blood was taken from each mouse three days before administration, and the total cholesterol (T-CHO) content was detected. The mice were randomly divided into two groups based on the T-CHO content, 7 mice in the control group administered with vehicle PBS, and 6 mice in the group administered with plasminogen. The first day of administration was set as Day 1. Mice in the group administered with plasminogen were injected with human plasminogen at a dose of 1 mg / 0.1 mL / mouse / day via the tail vein, and an equal volume of PBS was administered to mice in the control group administered with vehicle PBS via the tail vein, both lasting for 30 days. On ...

example 3

Plasminogen Lowers the Content of Serum Triglyceride in ApoE Atherosclerosis Mice

[0188]Thirteen 6-week-old male ApoE mice were fed with a high-fat and high-cholesterol diet (Nantong TROPHIC, TP2031) for 16 weeks to induce the hyperlipemia model[40, 41]. The model mice continued to be fed with a high-fat and high-cholesterol diet. 50 μL of blood was taken from each mouse three days before administration, and the total cholesterol (T-CHO) content was detected. The mice were randomly divided into two groups based on the T-CHO content, 7 mice in the control group administered with vehicle PBS, and 6 mice in the group administered with plasminogen. The first day of administration was recorded as Day 1. Mice in the group administered with plasminogen were injected with human plasminogen at a dose of 1 mg / 0.1 mL / mouse / day via the tail vein, and an equal volume of PBS was administered to mice in the control group administered with vehicle PBS via the tail vein, both lasting for 30 days. On ...

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Abstract

The present invention relates to a method for preventing atherosclerosis, comprising administeringh a prophylactically effective amount of plasminogen to a subject susceptible to atherosclerosis. The present invention further relates to a medicament, a pharmaceutical composition, an article of manufacture and a kit comprising plasminogen which are useful for preventing atherosclerosis.

Description

TECHNICAL FIELD[0001]The present invention relates to a method for preventing and / or treating a fat metabolism disorder and its related conditions, comprising administering an effective amount of plasminogen to a subject susceptible to or suffering from a fat metabolism disorder and its related conditions, to reduce an abnormal fat deposition in a body tissue and an organ, thereby achieving the purpose of preventing and / or treating a fat metabolism disorder and its related conditions and complications.BACKGROUND ART[0002]The fat metabolism disorder, also known as lipodystrophy, is one of metabolic diseases. It is the abnormality in lipids and lipid metabolites and the amounts thereof in blood and other tissues and organs, caused by primary or acquired factors. Lipid metabolism involves lipids being digested and absorbed in the small intestine, entering the blood circulation via the lymphatic system (via lipoprotein transport), being transformed by the liver, stored in adipose tissue...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K38/48A61P9/10
CPCA61K45/06A61P9/10A61K38/484C12Y304/21007A61P1/16Y02A50/30A61P3/06A61P3/10A61P9/00
Inventor LI, JINAN
Owner TALENGEN INTERNATIONAL LIMITED
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