Method for preventing and treating lipid metabolism disorders and related diseases thereof

Abstract

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 at various sites of the body, thereby achieving the purpose of preventing and / or treating a fat metabolism disorder and its related conditions or complications.

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...

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Benefits of technology

[0033]In yet another aspect, the present invention relates to a method for reducing the risk of atherosclerosis in a subject, comprising administering an effective amount of plasminogen to the subject. The present invention further relates to the use of plasminogen for reducing the risk of atherosclerosis in a subject. The present invention further relates to the use of plasminogen in the preparation of a medicament, a pharmaceutical composition, an article of manufacture, and a kit for reducing the risk of atherosclerosis in a subject. Furthermore, the present invention also relates to a plasminogen for reducing the risk of atherosclerosis in a subject. The present invention further relates to a medicament, a pharmaceutical composition, an article of manufacture, and a kit comprising plasminogen which are useful for reducing the risk of atherosclerosis in a subject.

[0034]In some embodiments, the subject suffers from hypertension, obesity, diabetes mellitus, chronic hepatitis, hepatic cirrhosis, renal injury, chronic glomerulonephritis, chronic pyelonephritis, nephrotic syndrome, renal insufficiency, kidney transplantation, uremia, hypothyroidism, obstructive cholecystitis, or obstructive cholangitis, or the subject takes a drug or hormone that affects fat metabolism. In some embodiments, the plasminogen reduces the risk of atherosclerosis in a subject in one or more ways selected from: lowering a total cholesterol level, a triglyceride level, and a low-density lipoprotein level in blood, and elevating a high-density lipoprotein level in blood.

[0056]In the case of fatty liver, 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 metabolism mainly takes place in the mitochondria. Fat is transported out of the cell mainly through the smooth endoplasmic reticulum. 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. Long-term hepatocyte degeneration will lead to regeneration disorder and necrosis of hepatocytes, and thus form liver fibrosis and hepatic cirrhosis.

[0058]The exact cause of atherosclerosis has not been determined. However, important pathogenic factors have been identified as hyperlipemia, hypertension, a history of smoking, a family history of atherosclerosis (suffering from the disease before the age of 60) or diabetes mellitus. Hyperlipemia can promote the formation of fatty streaks. Hypertension exerts a constant force on the arteries, accelerating the process of arterial occlusion and arteriosclerosis; therefore, it can increase the prevalence of atherosclerosis. Smoking can cause arterial contractions and restrict blood flow, thus setting the stage for arterial occlusion. Diabetes mellitus can also contribute to the development of atherosclerosis, especially in very small arteries.

[0091]Once synthesized (chemically or recombinantly), the plasminogen of the present invention can be purified according to standard procedures in the art, including ammonium sulfate precipitation, affinity column, column chromatography, high performance liquid chromatography (HPLC), gel electrophoresis and the like. The plasminogen is substantially pure, e.g., at least about 80% to 85% pure, at least about 85% to 90% pure, at least about 90% to 95% pure, or 98% to 99% pure or purer, for example free of contaminants such as cell debris, macromolecules other than the subject antibody and the like.

[0096]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.

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