WO2015064960A1 - Pharmaceutical composition for preventing or treating liver diseases, containing plasmalogen precursor, plasmalogen or plasmalogen analog as effective component - Google Patents

Abstract

The present invention relates to a pharmaceutical composition for preventing or treating liver diseases, containing a plasmalogen precursor, plasmalogen, or a plasmalogen analog as an effective component. More specifically, a plasmalogen precursor, or plasmalogen or a plasmalogen analog produced by metabolizing the plasmalogen precursor, can decrease accumulation of neutral fats in the liver, repress expressions of inflammatory cytokine genes, and prevent or treat liver diseases such as fatty liver, hepatitis and liver cirrhosis, etc. through fatty acids oxidation capacity increase of peroxisome.

Description

A pharmaceutical composition for the prevention or treatment of liver disease, which contains a plasmagen precursor, a plasmagen or a plasmagen analog as an active ingredient.

The present invention relates to a pharmaceutical composition and a health food composition containing a plasmagen precursor, plasmagen or an analog thereof as an active ingredient, which is provided for the prevention or treatment of liver diseases such as fatty liver, hepatitis and cirrhosis.

Liver is the organ that plays a central role in nutrient metabolism. Normal human liver weighs about 1,500g and if liver dysfunction is caused, it causes problems in nutrient metabolism of living body, making glucose into glycogen or protein into albumin. Liver abnormalities such as diversion or disassembly of unnecessary things and delivery to the bile juices occur.

In general, hepatitis, which causes inflammation of the liver, accounts for the majority of liver diseases, and according to aspects, it can be divided into acute hepatitis and chronic infection, depending on the cause, viral hepatitis, alcoholic hepatitis, and drug hepatitis. In addition, liver diseases caused by such abnormalities include fatty liver, hepatitis, cirrhosis, liver cancer, and the like. The mechanism of the progression of liver disease is not fully understood, but it is thought to develop into advanced liver disease such as fatty liver disease and cirrhosis due to secondary cell damage after primary fatty liver development. If controllable, the development of more serious liver disease could be prevented. In the treatment of liver disease, exercise, alcoholism, diet and treatment are treated in parallel, but there are no treatment methods established to date and fundamentally complete healing is difficult.

Commercially available liver medicines are usually those that have preventive light treatment effects for acute liver injury in animals or clinical trials, such as silymarin (regalon), UDCA (ursa), and PMC (niche). There is no effective drug.

Recently, it has been known that peroxisome, a cell organelle as well as mitochondria, plays an important role in the oxidation of fatty acids, and it has been reported that peroxysome dysfunction may cause fatty liver. Peroxysomes also break down reactive oxygen species and are essential for the synthesis of substances called bile acids and plasmaogens.

On the other hand, plasmagen is a kind of special phospholipids containing vinyl ether bonds and is known as a major constituent of cell membranes, as a signaling material, and an important role in maintaining cell function, such as showing an antioxidant effect.

Korean Laid-Open Patent Publication No. 10-2011-7015617 discloses a technique for treating or preventing aging diseases associated with increased membrane cholesterol such as degenerative neuropathy, cognitive impairment, osteoporosis, manic depression and vascular disease. Although disclosed, it does not mention the treatment or prevention of liver disease of the plasmagen as in the present invention.

Accordingly, the present inventors have found that the plasmalogen precursor, plasmalogen or plasmalogen analogues have an effect of inhibiting the accumulation of liver fat and expression of inflammatory genes, thereby preventing or treating liver disease containing the plasmalogen precursor, plasmalogen or the like. The present invention has been completed to provide a pharmaceutical composition and a health food composition.

The present invention relates to a composition containing a plasmagen precursor, a plasmagen and a plasmagen analog, the pharmaceutical composition and health food composition for preventing or treating liver disease by reducing liver fat accumulation and inhibiting expression of genes that cause inflammation in liver tissue. to provide.

The present invention can provide a pharmaceutical composition for preventing or treating liver disease containing one or two or more as an active ingredient in the group consisting of a plasmagen precursor, a plasmagen and a plasmagen analog.

The plasmagen precursor may be alkoxy glycerol in which C16 to C18 fatty alcohols are connected to an glycerol backbone through an ether bond. In particular, the alkoxy glycerol may be selected from the group consisting of betyl alcohol (Batyl Alcohol), chimyl alcohol (Chimyl Alcohol), ceracyl alcohol (Selachyl Alcohol) and mixtures thereof, but is not limited thereto.

More preferably, the alkoxy glycerol may be shark liver oil, the shark liver oil is also alkoxy glycerol and squalene consisting of betyl alcohol (Batyl Alcohol), chimyl alcohol (Chimyl Alcohol) and ceracyl alcohol (Selachyl Alcohol) Include.

The plasmagen precursor, plasmagen or plasmaloge analog may be characterized by reducing the accumulation of triglycerides, inhibiting inflammatory cytokine gene expression and increasing fatty acid oxidation of peroxysomes.

In addition, the liver disease may be selected from the liver disease group consisting of fatty liver, hepatitis and cirrhosis.

The plasmagen precursor, plasmagen or plasmalogen analog may include 0.01 to 90 parts by weight based on 100 parts by weight of the total pharmaceutical composition.

In another embodiment, the present invention may be provided as a health food composition for improving or preventing liver disease containing any one or two or more selected from the group consisting of a plasmagen precursor, a plasmagen and a plasmagen analog as an active ingredient.

According to the present invention, the plasmagen precursor or plasmagen generated by metabolizing the plasmagen precursor reduces the accumulation of triglycerides in liver tissue, inhibits the expression of inflammatory cytokine genes, and the fatty acids by peroxysomes. Increasing the oxidative capacity can prevent or treat liver diseases such as fatty liver, hepatitis and cirrhosis.

1 is alanine aminotransfer of plasma of a group of mice treated with MCDD (methionine-choline deficient diet) -treated mice and 100 mg / kg / day of plasmalogen precursor alkoxy glycerol, which is a non-alcoholic steatohepatitis generation model. This is a graph showing the change of the raise (ALT) value. P *** <0.001 vs control (CON); P # <0.05 vs MCDD.

Figure 2 is a graph showing the change in the amount of triglycerides in the liver of the MCDD treated rat group and the rat group in which MCDD and the plasma rosen precursor alkoxy glycerol 100 mg / kg / day together. P * <0.05 vs control; P # <0.05 vs MCDD.

Figure 3 is a graph showing the changes in gene expression of inflammatory cytokines in the MCDD treated mice group and the rat group fed MCDD and plasmalogen precursor alkoxy glycerol 100 mg / kg / day. P * <0.05 vs control; P # <0.05 vs MCDD.

Figure 4 shows the results of the liver histological changes of the MCDD treated mice group and the rat group ingested MCDD and plasmalogen precursor alkoxy glycerol 100 mg / kg / day.

Figure 5 shows the change of liver tissue fatty acid oxidation ability of MCDD treated mice group and the rat group ingested MCDD and plasmalogen precursor alkoxy glycerol 100 mg / kg / day, the left side is mitochondrial fatty acid oxidation on the right side peroxy A graph showing some fatty acid oxidation. P * <0.05 vs control; P # <0.05 vs MCDD.

Figure 6 shows the results of liver histological changes in the MCDD-treated rat group and the administration group (AG-200) in combination with MCDD and the plasmalogen precursor alkoxy glycerol 200 mg / kg / day and confirmed the liver triglycerides and plasma ALT levels It is a graph.

The present invention can provide a pharmaceutical composition for preventing or treating liver disease, which contains any one or two or more selected from the group consisting of a plasmagen precursor, a plasmagen or a plasmagen analog.

The plasmagen precursor may be alkoxy glycerol in which C16 to C18 fatty alcohols are connected to an glycerol backbone through an ether bond. In particular, the alkoxy glycerol may be selected from the group consisting of betyl alcohol (Batyl Alcohol), chimyl alcohol (Chimyl Alcohol), ceracyl alcohol (Selachyl Alcohol) and mixtures thereof, but is not limited thereto.

More preferably, the alkoxy glycerol may be shark liver oil, the shark liver oil is also alkoxy glycerol and squalene consisting of betyl alcohol (Batyl Alcohol), chimyl alcohol (Chimyl Alcohol) and ceracyl alcohol (Selachyl Alcohol) Include.

In one embodiment, the plasmagen or plasmalogen analog may be orally administered in the form of a precursor alkyl glycerol to be converted into a plasmalogen or plasmalogen analog form.

The plasmagen precursor, plasmagen or plasmagen or analogs thereof may reduce the accumulation of triglycerides, inhibit inflammatory cytokine gene expression and increase fatty acid oxidation of peroxysomes.

The liver disease may be selected from the group of liver diseases consisting of fatty liver, hepatitis and cirrhosis.

More specifically, to determine the degree of inflammation and damage of hepatocytes in the plasma of the experimental group administered only a fatty liver-induced diet (MCDD) and the experimental group administered a plasma alkoxy glycerol precursor to the fatty liver-induced diet (MCDD) As a result of measuring alanine aminotransferase (ALT), respectively, the experimental group administered with the plasma alkoxy glycerol precursor showed significant improvement compared to MCDD, and real-time gene amplification of liver tissue, As shown in FIG. 3, inflammatory cytokine gene expression was suppressed. From this, it could be confirmed that the plasmagen or an analog thereof has a good effect on preventing or treating hepatitis and cirrhosis.

In addition, the triglycerides in the liver were confirmed through measurement of triglycerides, and as shown in FIG. 2, the experimental group administered with alkoxy glycerol, which is a plasmagen precursor, in the fatty liver-induced diet showed similar results to the normal diet control, and liver tissue staining as shown in FIG. 4. In the results, it was confirmed that the improvement was similar to the control group. From this, it was confirmed that the plasmagen or an analog thereof has an excellent effect in preventing or treating fatty liver.

The plasmagen precursor, plasmagen or plasmalogen analog may include 0.01 to 90 parts by weight based on 100 parts by weight of the total pharmaceutical composition.

In one embodiment of the present invention, the pharmaceutical composition for preventing or treating liver disease containing the plasmalogen or an analog thereof as an active ingredient is an injection, granule, powder, tablet, pill, capsule, suppository, gel according to a conventional method. Any one of the formulations selected from the group consisting of suspensions, emulsions, drops or solutions can be used.

In another embodiment of the present invention, a pharmaceutical composition for preventing or treating liver disease containing a plasmagen precursor, a plasmagen or a plasmagen analog as an active ingredient is an appropriate carrier, excipient, or shelf-use which are commonly used in the preparation of the pharmaceutical composition. One or more additives selected from the group consisting of releases, sweeteners, coatings, swelling agents, lubricants, lubricants, flavoring agents, antioxidants, buffers, bacteriostatic agents, diluents, dispersants, surfactants, binders and lubricants may be further included. .

Specifically, the carriers, excipients and diluents are lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, microcrystalline Cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil can be used, and solid preparations for oral administration include tablets, pills, powders, granules, capsules. And the like, and such solid preparations may be prepared by mixing at least one excipient such as starch, calcium carbonate, sucrose or lactose, gelatin and the like in the composition. In addition to simple excipients, lubricants such as magnesium styrate and talc may also be used. Oral liquid preparations include suspensions, solvents, emulsions, syrups, and the like, and may include various excipients such as wetting agents, sweeteners, fragrances, and preservatives, in addition to commonly used simple diluents such as water and liquid paraffin. Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations, suppositories, and the like. As the non-aqueous solvent and suspending agent, propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate and the like can be used. Witsol, macrogol, tween 61, cacao butter, laurin butter, glycerogelatin and the like may be used as the base material of the suppository.

According to one embodiment of the invention the pharmaceutical composition is intravenous, intraarterial, intraperitoneal, intramuscular, intraarterial, intraperitoneal, intrasternal, transdermal, nasal, inhaled, topical, rectal, oral, intraocular or intradermal Via the route can be administered to the subject in a conventional manner.

The preferred dosage of the plasmagen precursor, plasmagen or plasmaloge analog may vary depending on the condition and weight of the subject, the type and severity of the disease, the form of the drug, the route of administration and the duration and may be appropriately selected by those skilled in the art. According to one embodiment of the present invention, but not limited thereto, the daily dosage may be 0.01 to 200 mg / kg, specifically 0.1 to 200 mg / kg, more specifically 0.1 to 100 mg / kg. Administration may be administered once a day or divided into several times, thereby not limiting the scope of the invention.

In the present invention, the 'subject' may be a mammal including a human, but is not limited thereto.

In another embodiment, the present invention may be provided as a health food composition for improving or preventing liver disease, which contains one or two or more of the plasmagen precursor, the plasmagen and the plasmagen analog as an active ingredient.

The health food may be provided in the form of a powder, granules, tablets, capsules, syrups or beverages, wherein the health food is an active ingredient other foods or food additives in addition to the plasmaloge precursor, plasmalogen or plasmaloge analogs according to the present invention. It may be used together with, and may be suitably used according to a conventional method. The mixed amount of the active ingredient can be suitably determined depending on the purpose of use thereof, for example, prophylactic, health or therapeutic treatment.

The effective dose of the plasmagen precursor, plasmagen or plasmaloge analogs contained in the health food may be used in accordance with the effective dose of the pharmaceutical composition, but for long term intake for health and hygiene purposes or for health control purposes. In the case of may be below the above range, it is clear that the active ingredient can be used in an amount above the above range because there is no problem in terms of safety.

There is no particular limitation on the kind of the health food, for example, meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, gums, dairy products including ice cream, various soups, drinks, tea, Drinks, alcoholic drinks, vitamin complexes, etc. are mentioned.

Hereinafter, examples will be described in detail to help understand the present invention. However, the following examples are merely to illustrate the content of the present invention is not limited to the scope of the present invention. The embodiments of the present invention are provided to more completely explain the present invention to those skilled in the art.

The following reference examples are provided to provide a reference example that is commonly applied to each embodiment according to the present invention.

Reference Example

1. Experimental Animals and Reagents

MCD feed for fatty hepatitis was purchased from Dyets (Bethlehem, PA, USA). Alkali glycerol (betayl alcohol), a plasmagen precursor, was purchased from Sigma (St Louis, MO, USA).

2% BSA was added to the DMEM: F12 medium, and the plasmagenogen precursor alkoxy glycerol dissolved in ethanol was added thereto, followed by conjugation by confirming that crystals disappeared after incubation at 70 ° C. for 20 minutes. Seven-week-old C57 / BL6 male mice were stabilized for 7 days after the experimental animals were placed in the experimental room, and the control group, the normal diet group, the MCD diet group (MCDD group), the MCD diet and the plasmagen precursor alkoxy glycerol 100 mg / kg / day (Group AG) 6 mice were distributed in each group. After ingesting the experimental feed for a total of 6 weeks, only water was consumed for 12 hours, and then blood samples were taken and liver tissues were extracted at the expense of experimental rats. The isolated liver tissue was immediately frozen in dry ice and stored with plasma in -70 ° C freezer.

Example 1 Blood Sample Measurement

Blood samples were collected from the vena cava of experimental animals, and plasma was separated using a centrifuge (300 rpm, 15 minutes) and measured for alanine aminotransferase (ALT) using a kit from Labs Biotechnology (London, Canada). . ALT is a marker that sensitively reflects the degree of inflammation and damage of liver cells, and is widely used to identify various liver diseases such as hepatitis and cirrhosis as well as fatty liver. The change in plasma ALT of each experimental group was significantly improved in the AG group administered with the MCD diet and the plasmalogen precursor alkoxy glycerol 100 mg / kg / day as shown in Figure 1 compared to the MCDD group.

Example 2 Measurement of Triglycerides in Liver Tissue

Triglycerides in liver tissue were measured by purchasing a triglyceride (GPO-Trinder) kit from Sigma. The ground liver tissue and plasma were reacted with the extraction buffer for 4 hours at room temperature, and then centrifuged at 1000 rpm for 10 minutes by adding 1N H ₂ SO _4. After removing the supernatant, 100 mg of Na ₂ S ₂ O ₂ was added to the remaining solution. The mixture was further centrifuged at 1000 rpm for 5 minutes. Thereafter, a supernatant was obtained, 0.5 g of silicic acid was added, the reaction was performed at room temperature for 5 minutes, centrifuged at 1000 rpm for 10 minutes, and the sample obtained by evaporating the supernatant with N ₂ gas was dissolved with isopropanol. Thereafter, triglyceride reagent A was added thereto, and reacted at room temperature for 5 minutes, and then measured at 540 nm using an Emax precision micro plate reader (Molecular Devices, Sunnyvale, CA). The change in triglyceride content of liver tissue in each experimental group is shown in FIG. 2, and the results were improved in the AG group administered with the MCD diet and the plasmalogen precursor alkoxy glycerol 100 mg / kg / day as in the plasma ALT.

Example 3 Inflammatory Changes in Liver Tissue

Real-time gene amplification of gene expression of tumor necrosis factor (TNF-α) and macrophage chemotactic protein-1 (MCP-1), a representative inflammatory cytokine, to determine the degree of inflammation in liver tissue It was confirmed by (real-time PCR) method. As a result, referring to FIG. 3, it was confirmed that the administration of the plasmaogen precursor alkoxy glycerol 100 mg / kg / day, as well as the plasma ALT and triglyceride content in the liver, inhibited inflammatory cytokine gene expression increased by the MCD diet.

Example 4 Histological Observation

Some of the isolated liver tissues were fixed with 10% neutral formalin solution, embedded in paraffin, washed formaldehyde in running water for at least 12 hours, then 1 hour in 60% ethanol, 1 hour in 70% ethanol, 1 in 80% ethanol. Water was washed stepwise at 1 hour in 90% ethanol, 1 hour in 5% ethanol, and 1 hour in 100% ethanol. Afterwards, a total of three transparent processes, one hour in xylene and two infiltrations, one hour in paraffin, were embedded and a section of about 4 ㎛ thick was prepared.

Sections were analyzed by light microscopy with hematoxylin-eosin (H & E) and trichrome C staining.

Representative H & E and trichrome C staining pictures of the liver tissues of the control group, MCDD group and AG group are as shown in Figure 4, the fatty acid hepatitis by MCD diet 100 mg / kg / day plasmalogen precursor alkyl glycerol to a level similar to the control group You can see the improvement.

Example 5 Fatty Acid Oxidation Measurement

In order to measure the inter-tissue fatty acid oxidation from the ¹⁴ C- palmitate (NEN Life Sciences, Boston, MA , USA) and analyzed by measuring the amount of ¹⁴ CO ₂ is generated.

To this end, 50 μl of liver grinding solution was added with a reaction buffer containing 0.2 mM palmitate (1- ¹⁴ C-palmitate at 0.5 μCi / ml) and reacted at 30 ° C. for 2 hours.

Thereafter, 50 µl of 4N sulfuric acid as a stop buffer was added thereto, and the resultant was reacted for 2 hours, and then ¹⁴ CO ₂ production was measured. To investigate the fatty acid oxidation of peroxysomes responsible for fatty acid beta oxidation in addition to mitochondria, 12.5 μM of mitochondrial inhibitors rotenone and 100 μM of antimycin were combined with 0.2 mM palmitate (1- ¹⁴ C palmitate at 0.5 μCi / ml). Put in the reaction buffer and reacted for 2 hours at 30 ℃. Thereafter, 50 µl of 4N sulfuric acid, which is a stop buffer, was added and reacted for 2 hours, and then ¹⁴ CO ₂ was measured.

 As a result, the oxidation of peroxysome fatty acid in liver tissue of each experimental group as shown in FIG. 5 was confirmed.

Example 6 Plasma Rosen Precursor Effect in High Fat Diet Fatty Liver Animal Model

MCDD (methionine-choline deficient diet) animal model represents non-alcoholic steatohepatitis, but it does not represent the risk factors associated with metabolic syndrome. To overcome this limitation, we compared the liver tissue of rats fed high fat diet (HFD) as a general animal model for hepatic steatosis.

Unlike MCDD, this animal model showed only fatty liver disease with no inflammatory response.

Changes were confirmed by administering a plasma alkoxy glycerol precursor, a high-fat diet, to induce obesity and non-alcoholic fatty liver in the animal model.

First, the control group (CON) was fed a general diet consisting of 7% fat, 18% protein and 75% carbohydrate in the 7-week-old C57 / BL6 male mice, and the experimental group (HFD) was 60% fat, 18% protein, 22% High fat diet (HFD) consisting of carbohydrates was ingested without dietary restriction.

In addition, the alkoxy glycerol administration group (AG-200) was ingested by mixing 200 mg / kg / day of alkoxy glycerol in a high fat diet. After ingesting the feed to each experimental group for a total of 12 weeks, liver histological changes were confirmed in the same manner as in Example 4, and plasma ALT levels were confirmed in the same manner as in Example 1.

As a result, as shown in FIG. 6, it was confirmed that fatty liver development and lipid content were remarkably improved in the liver tissues of the high-fat diet (HFD) and the administration group (AG-200) administered together with the alkoxy glycerol. A significant decrease was found.

Hereinafter, the formulation examples of the pharmaceutical composition of the present invention will be described, but the present invention is not intended to be limited thereto, but is intended to be described in detail.

Preparation Example 1 Preparation of Injection

10 ml of plasmalogen, 3.0 mg of sodium metabisulfite, 0.8 mg of methylparaben, 0.1 mg of propylparaben, and sterile distilled water for injection are mixed and prepared in a conventional manner to a final volume of 2 ml, followed by a 2 ml ampoule Injections were made by filling into and sterilizing.

Preparation Example 2 Preparation of Tablet

Tablets were prepared by mixing 10 mg of bent alcohol, 100 mg of lactose, 100 mg of starch, and magnesium stearate in appropriate amounts and tableting according to a conventional tablet preparation method.

Preparation Example 3 Preparation of Capsule

A capsule was prepared by mixing 10 mg of bent alcohol, 50 mg of lactose, 50 mg of starch, 2 mg of talc, and magnesium stearate, and filling into a gelatin capsule according to a conventional capsule preparation method.

Hereinafter, an example of preparing a health food using plasmalogen or an analog thereof according to the present invention will be described, but it is not intended to limit the present invention but merely to explain in detail.

Preparation Example 1 Preparation of Health Food

10 mg of betyl alcohol, vitamin mixture (70 μg of vitamin A acetate, 1.0 mg of vitamin E, 0.13 mg of vitamin B, 0.15 mg of vitamin B 2, 0.5 mg of vitamin B 6, 0.2 μg of vitamin B 12, vitamin C 10 mg, biotin 10 µg, nicotinic acid amide 1.7 mg, folic acid 50 µg, calcium pantothenate 0.5 mg, mineral mixture (1.75 mg ferrous sulfate, 0.82 mg zinc oxide, 25.3 mg magnesium carbonate, 15 mg potassium monophosphate, calcium diphosphate dibasic) 55 mg, potassium citrate 90 mg, calcium carbonate 100 mg, magnesium chloride 24.8 mg) were mixed, granules were prepared, and health food was prepared according to a conventional method.

Preparation Example 2 Preparation of Health Beverage

Add 10 mg of shark liver oil, 1000 mg of citric acid, 100 g of oligosaccharide, 2 g of plum concentrate, 1 g of taurine, and purified water to make a total of 900 ml, and mix the above ingredients according to a conventional healthy beverage preparation method, and then, about 1 After stirring and heating at 85 ° C. for an hour, the resulting solution was collected by filtration into a sterilized 2 L container, sealed sterilized and then refrigerated.

Claims (8)

1. A pharmaceutical composition for the prevention or treatment of liver disease, comprising any one or two or more selected from the group consisting of a plasmagen precursor, a plasmagen and a plasmagen analog as an active ingredient.
2. The method of claim 1, wherein the plasmagen precursor is alkoxy glycerol (alkoxy glycerol) connected to the glycerol backbone (C16 to C18 fatty alcohols through an ether bond) or Therapeutic pharmaceutical composition.
3. The liver disease of claim 2, wherein the alkoxy glycerol is selected from the group consisting of betyl alcohol, chimyl alcohol, ceracyl alcohol, and mixtures thereof. Prophylactic or therapeutic pharmaceutical composition.
4. 4. The pharmaceutical composition for preventing or treating liver disease according to claim 3, wherein the alkoxy glycerol is shark liver oil.
5. The liver disease according to claim 1, wherein the plasmagen precursor, plasmagen or plasmaloge analog decreases accumulation of triglycerides, inhibits inflammatory cytokine gene expression and increases fatty acid oxidation of peroxysomes. Prophylactic or therapeutic pharmaceutical composition.
6. [Claim 2] The pharmaceutical composition for preventing or treating liver disease according to claim 1, wherein the plasmagen precursor, plasmagen or plasmagen analog is contained in an amount of 0.01 to 90 parts by weight based on 100 parts by weight of the pharmaceutical composition.
7. The pharmaceutical composition for preventing or treating liver disease according to claim 1, wherein the liver disease is liver disease selected from the group consisting of fatty liver, hepatitis and cirrhosis.
8. Health food composition for improving or preventing liver disease containing any one or two or more selected from the group consisting of a plasmaogen precursor, a plasmaogen and a plasmagen analog.

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