KR20220018838A - Composition for Prolhylaxis or Treatment of Liver Disease Comprising Paprika Extract - Google Patents

Abstract

The present invention relates to a composition that can be safely taken without fear of toxicity as a food material, and has a hepatoprotective effect, so that it can be usefully used for preventing or treating/alleviating symptoms of liver disease. More specifically, the present invention relates to a composition for preventing or treating/alleviating symptoms of liver dysfunction or liver disease containing a paprika extract as an active component.

Description

A composition for preventing or treating liver disease containing paprika extract {Composition for Prolhylaxis or Treatment of Liver Disease Comprising Paprika Extract}

The present invention relates to a composition that can be safely taken without concern about toxicity as a food material, and has hepatoprotective effect, so that it can be usefully used for preventing or treating/improving symptoms of liver disease.

The liver is one of the important organs of the human body that is responsible for the body's metabolic process, which appropriately transforms the ingested food into the form of nutrients required by various tissues, and processes the waste products remaining after being used by the tissues. Specifically, it secretes bile, a digestive juice, metabolizes proteins, carbohydrates, and fats, stores glycogen and fat-soluble vitamins, synthesizes blood clotting factors, removes wastes and toxic substances from the blood, regulates blood volume, and senescence It performs functions such as destroying one red blood cell.

Various factors, such as mental stress, excessive intake of food or alcohol containing fat, viral infection, drugs or smoking, exposure to harmful substances such as pollutants, and malnutrition, can cause liver dysfunction. In addition, liver failure can cause abnormalities in the immune system as the human body cannot detoxify defenses and cause other diseases. Liver dysfunction causes a variety of symptoms, such as weakness, low blood pressure, frequent strains and bleeding, tremors, bluntness, EEG changes, and fluid accumulation in the abdominal cavity.

In order to differentiate various diseases related to the liver, it is necessary to comprehensively interpret several biochemical tests. For this, several test items are collectively referred to as liver function tests. Major tests include AST (aspartate aminotransferase), ALT (alanine aminotransferase), ALP (alkaline phosphatase), GGT (gamma-glutamyltransferase), and bilirubin. In addition, total protein, albumin In some cases, items such as lactate dehydrogenase (LDH) and ammonia are added to the test. Among them, AST (GOT) and ALT (GPT) are enzymes present in liver cells, and are mainly released into the blood when hepatocytes are damaged. Therefore, blood AST and ALT levels can be used as markers of liver damage.

Since the liver is an organ with a large buffering capacity, symptoms do not appear in the early stages of the disease, and because there are few nerves that feel pain, it is usually discovered only after a significant deterioration. Cirrhosis or liver cancer is the last stage commonly reached when various liver diseases progress chronically, and the liver is a very important organ for early health management. Accordingly, studies have been conducted to provide a composition for liver protection using natural substances that can be safely used. For example, Registered Patent No. 10-0633851 discloses a composition for liver protection or prevention and treatment of liver disease containing heat-dried wild garlic extract as an active ingredient, and Registered Patent No. 10-1106499 discloses an extract of hepatica sprigs. A food composition for hepatoprotective effect comprising: Patent Registration No. 10-1402058 discloses a composition for preventing or treating liver disease containing a fermented cheonggukjang turmeric extract or a curcuminoid derivative isolated therefrom.

Paprika is a modified pepper with a lot of flesh. In the West, it is called sweet pepper, and it is recognized as the same item, but in Korea, it is treated as different because of the difference in color and thickness of the flesh. Paprika is rich in antioxidants such as vitamin C, which is effective in preventing aging, strengthening immunity, preventing cancer, treating allergies or asthma, and recovering from fatigue. It is also useful for vascular diseases. In addition, it contains a large amount of vitamin A and beta-carotene to prevent presbyopia and has the effect of preventing eye fatigue. However, efficacy related to liver disease has not been reported yet.

Registered Patent No. 10-0633851 Registered Patent No. 10-1106499 Registered Patent No. 10-1402058 Registered Patent No. 10-1418239

An object of the present invention is to provide a composition that can be safely used without side effects and is effective for liver protection and improvement of liver function.

The present invention for achieving the above object relates to a pharmaceutical composition for preventing or treating liver dysfunction or liver disease comprising a paprika extract as an active ingredient.

The composition of the present invention effectively reduced AST and ALT, which are indicators of liver function test, in an experiment on an animal model of liver damage, and it was confirmed that there was an effect of protecting the liver and improving liver function. In addition, it was confirmed that it was effective in preventing or treating fatty liver and diseases caused by the progression of fatty liver by inhibiting the accumulation of fat in the liver tissue.

In the present invention, 'paprika extract' means that the ratio of some components is increased compared to raw paprika itself by processing paprika. Included in the category of extracts. In the present invention, 'paprika extract' may be prepared by a conventional method for producing a plant extract. In the case of extraction using a solvent, cold extraction, heat extraction, ultrasonic extraction, supercritical extraction, etc. may be used, but the present invention is not limited thereto.

In an embodiment of the present invention, after extraction using various solvents, carotenoids were analyzed. As a result, capsanthin was contained in the largest amount, accounting for about 2/3 of the total carotenoid content. Therefore, hepatoprotective efficacy was evaluated for the non-polar solvent extract with the highest carotenoid content. The extract showed that the higher the content of capsanthin, the better the hepatoprotective activity, and it was justified to set capsanthin as an indicator component. Although capsanthin itself also exhibited hepatoprotective activity, paprika extract exhibited significant hepatoprotective activity compared to that expected from capsanthin or total carotenoid content. This is because ingredients other than capsanthin and carotenoids extracted together with capsanthin under favorable conditions for capsanthin extraction contribute to the excellent hepatoprotective activity of the hepatoprotective paprika extract, or the composition of paprika's own carotenoids has a synergistic effect. By showing, it was suggested that the outstanding hepatoprotective activity was shown.

Therefore, when extracting the extract of the present invention using a solvent, it is more preferable to use a non-polar solvent extract. In addition, for efficient extraction, it is more preferable to extract after crushing or grinding. Examples of the non-polar solvent include C5 to C8 alkanes, C1 to C3 haloalkanes, C2 to C6 ethers or C2 to C6 esters, and more specifically, pentane, hexane, hexane, octane, chloroform, methylene chloride. , diethyl ether, and ethyl acetate, but are not limited thereto. The extract of the non-polar solvent may be extracted after grinding raw paprika and adding a non-polar solvent, or it may be extracted after obtaining the dried paprika or C1-C4 alcohol extract. In addition, the extract may be additionally fractionated to further concentrate the active ingredient having the effect on hepatoprotection and liver function improvement.

The extract obtained by squeezing or extraction with a solvent may be used as it is, concentrated, or dried. It goes without saying that the drying method may also be a conventional method such as spray drying, heat drying, or freeze drying.

In addition, since it was confirmed that capsanthin set as an indicator material also exhibits hepatoprotective efficacy as described above, the present invention provides a pharmaceutical composition for preventing or treating liver dysfunction or liver disease comprising capsanthine as an active ingredient. .

The composition of the present invention may be prepared by a method known in the pharmaceutical field for use as a medicament for the prevention or treatment of liver dysfunction or liver disease, itself or a pharmaceutically acceptable carrier (carrier), excipient (forming agent), a diluent, etc. may be mixed and used. In addition, the composition of the present invention may be used as a single ingredient, or in combination with other active ingredients effective for the prevention or treatment of liver dysfunction or liver disease, and may be used as a drug for combined treatment. The composition of the present invention may be formulated as a formulation for oral or parenteral administration and used as a medicament for the prevention or treatment of liver dysfunction or liver disease. The dosage of the active ingredient according to the present invention may be appropriately selected according to the absorption of the active ingredient in the body, the form of the preparation, the age, sex and condition of the patient, the severity of symptoms, etc., and the administration may be administered once a day. , may be administered in several divided doses. A typical dosage is 0.001mg/kg·day to 10g/kg·day. Since the composition of the present invention can be safely used without toxicity and side effects, it can be safely used even when taken for a long period of time for prophylactic purposes.

In addition, the present invention relates to a health functional food composition for liver protection or liver function improvement comprising a paprika extract as an active ingredient. Like the pharmaceutical composition, the present invention as well as paprika extract provides a health functional food composition for liver protection or liver function improvement comprising capsanthin as an active ingredient.

The health functional food composition of the present invention may be added to the health functional food of the present invention in an amount of preferably 0.01 to 100% by weight. The effective dose of the health functional food composition of the present invention can be used according to the effective dose of the pharmaceutical composition, but in the case of long-term intake for health and hygiene or health control, it may be less than the above range. , the active ingredient can be used in an amount beyond the above range because there is no problem in terms of safety. The health functional food of the present invention includes the form of powder, granule, tablet, capsule, pill or liquid, and the like, and the food to which the composition of the present invention can be added includes, for example, various foods, beverages, gum, There are tea, sweets, alcoholic beverages, chocolate, vitamin complexes, and health functional foods. Alternatively, the health functional food of the present invention may be used in the form of a seasoning that can be used when cooking food by itself or by mixing with other ingredients. For example, the composition in powder or granular form has the effect of enriching taste and color as well as exhibiting liver protection or liver function improvement activity by adding it during the preparation of salads or side dishes.

As described above, since the composition of the present invention contains paprika extract, which has been used as food for a long time, as an active ingredient, it can be safely used without concerns about toxicity or side effects even when taken for a long period of time, so it can be usefully used for preventing or treating/improving symptoms of liver disease. can

1 is a graph showing the hepatoprotective effect of paprika extract.
Figure 2 is an H&E staining image of liver tissue showing the hepatoprotective effect of paprika extract.
3 is an Oil-Red O staining image showing the hepatoprotective effect of paprika extract.
Figure 4 is a graph showing the effect of paprika extract administration on blood cholesterol concentration.

Hereinafter, the present invention will be described in more detail with reference to the accompanying examples. However, these embodiments are merely examples for easily explaining the content and scope of the technical idea of the present invention, and thereby the technical scope of the present invention is not limited or changed. It will be natural for those skilled in the art that various modifications and changes can be made within the scope of the technical spirit of the present invention based on these examples.

[Example]

Example 1: Preparation of paprika extract

Preparation Example 1: Preparation of paprika powder (P)

Remove the stem of Raon Red Paprika, wash thoroughly, and then drain the water. A 100 kg sample was ground using a blender, and this was freeze-dried to obtain 10.5 kg of paprika powder.

Preparation Example 2: Preparation of paprika hexane extract (CRE)

10 times (v/w) of n-hexane was added to 8.5 kg of the paprika powder prepared in Preparation Example 1, and the mixture was extracted by stirring at 25° C. for 12 hours. After stirring, insoluble matter was filtered off and concentrated to obtain 168 g of a hexane extract.

Example 2: Index component setting

Active ingredient analysis of carotenoid-based compounds was performed in order to set a component serving as an indicator of the paprika extract prepared in Example 1. To this end, the content of carotenoid compounds in the extract was analyzed by HPLC using 12 carotenoids as reference materials, and the results are shown in Table 1 below.

As can be seen in Table 1, the carotenoid-based compound is contained in a weight ratio of 0.05% in the powder of Preparation Example 1 and 3.18% in the extract of Preparation Example 2, among which the content of capsanthin is the total carotenoid-based compound content It was overwhelmingly dominant, accounting for about 2/3 of the Accordingly, extraction efficacy using various solvents was analyzed using capsanthin as an indicator component.

To this end, 20 times alcohol was added to 789 g of paprika powder prepared in Preparation Example 1, and the mixture was extracted by stirring at 80° C. for 3 hours. The insoluble matter was filtered off, concentrated, and dried in vacuo to prepare an EtOH extract. 10 times purified water was added to the EtOH extract to dissolve, and the same amount of purified water as n-hexane (n-hexane), ethyl acetate (EtOAc) and n-butyl alcohol (n-BuOH) was used to sequentially extract. Extraction of each fraction was repeated three times. Each extract was concentrated and dried to obtain each organic solvent fraction. Preparation Example 1 Sample standard yield of the obtained fraction and the content of capsanthin set as an indicator material were quantified and shown in Table 2 below.

It can be confirmed that capsanthin is efficiently extracted from a non-polar solvent rather than a polar solvent.

Example 3: Evaluation of hepatoprotective efficacy of paprika extract

The effect of paprika extract on liver damage caused by a high-fat diet was evaluated.

Male ApoE knock out mice aged 8-12 weeks and weighing about 25 g were bred under constant conditions (temperature: 22±2°C, humidity: 50±5%, contrast: 12 hours light/dark cycle) in an animal room. The experimental group consisted of 8 to 10 animals in each group, and the specified diet and the specified drug were administered to each group for 12 weeks. Diet was voluntarily and without restriction along with water, and the designated drug for each group was orally administered once a day. The classification of the experimental group is as follows.

① Negative control group (ND) - Normal diet

② Positive control group (WD) - high fat diet (Western diet, 0.2% cholesterol, 21% fat, Harlan)

③ Experimental group 1 (P) - High-fat diet + Preparation Example 1 powder (25 mg/kg·day)

④ Experimental group 2 (CRE) - High fat diet + Preparation Example 2 extract (25 mg/kg·day)

⑤ Experimental group 3 (CAP) - High-fat diet + Capsanthin (0.5 mg/kg/day, Cayman Inc.)

⑥ Comparative group (A) - High fat diet + Atorvastatin (20 mg/kg·day)

At the end of the diet, mice were sacrificed, blood was collected from the heart, and liver tissue was collected and analyzed.

Measure the AST and ALT levels in the blood using a blood biochemical analyzer (BS220, Mindray) with the plasma obtained from the collected blood. The results are shown in FIG. 1 .

The ALT and AST levels of the positive control group were significantly increased (#p<0.05 vs ND) compared to the negative control group, indicating that liver damage was induced by the high-fat diet. Both ALT and AST levels of the experimental group administered with the paprika extract of Preparation Example 2 were similar to those of the negative control group, and significantly decreased (*p<0.05 vs WD) compared to the positive control group, indicating the best efficacy. The experimental group administered with the powder of Preparation Example 1 did not show significance at the p<0.05 level, but ALT and AST levels were significantly reduced compared to the positive control group. In the present invention, the experimental group administered with capsanthin set as an indicator material of paprika extract also reduced both ALT and AST levels, and the ALT level showed significance. When the dosage of the powder of Preparation Example 1 and the extract of Preparation Example 2 is converted into the content of capsanthin, it is 0.008 mg/kg·day and 0.5 mg/kg·day, respectively. Comparing with the ALT and AST values in the third experimental group to which capsanthin was administered, it can be confirmed that the paprika extract exhibits excellent efficacy on hepatoprotection compared to that expected from the capsanthin content in the paprika extract. This means that components exhibiting efficacy other than capsanthin are included in the paprika extract, or a synergistic effect is exhibited by combination with other compounds included in the paprika extract.

2 and 3 are images observed under a microscope after the harvested liver tissue was fixed in 10% formalin and tissue section slides were prepared and stained with H&E and Oil-Red O, respectively, white in FIG. 2 and red in FIG. 3 The color indicates the fat accumulated in the liver tissue. It can be seen that the fat accumulated in the liver tissue was significantly increased by the high-fat diet, and the fat accumulation was greatly reduced by the administration of the paprika extract or capsanthin, which is an indicator component. Compared with the control group administered with Atorvastatin, which is a therapeutic agent for hyperlipidemia and has an effect on fatty liver, the first experimental group simply administered with a freeze-dried powder of paprika showed a similar degree of fat accumulation as the control group, and the extract or cap of Preparation Example 2 In the 2nd and 3rd experimental groups administered with xanthine, fat accumulation was significantly reduced compared to Atorvastatin.

To determine whether the hepatoprotective effect of the paprika extract is closely related to the effect of lowering fat decomposition or absorption, blood cholesterol levels were measured. 4 is a graph showing the results, and the blood cholesterol concentration showed the lowest value in the comparison group for all three indicators of total cholesterol, LDL, and total triglyceride. This conflicts with the hepatoprotective effect of FIGS. 1 to 3, and although the paprika extract has the effect of decomposing or inhibiting absorption of cholesterol, it is considered that it is not the main mechanism of the hepatoprotective effect of paprika.

Although the present invention has been described in detail with reference to preferred embodiments so far, the present invention is not limited to the above-described embodiments, and in the technical field to which the present invention pertains without departing from the spirit of the present invention as claimed in the claims It should be understood that the technical spirit of the present invention extends to the extent that various variations or modifications can be made by those of ordinary skill in the art.

Claims (8)

A pharmaceutical composition for preventing or treating liver dysfunction or liver disease, comprising a paprika extract as an active ingredient.
The method according to claim 1,
The paprika extract is a pharmaceutical composition for the prevention or treatment of liver disease, characterized in that the dried powder of paprika.
The method according to claim 1,
The extract is a pharmaceutical composition for preventing or treating liver dysfunction or liver disease, characterized in that the fraction containing capsanthin.
4. The method according to claim 3,
The paprika extract is a pharmaceutical composition for preventing or treating liver dysfunction or liver disease, characterized in that it is a non-polar solvent extract.
5. The method of claim 4,
The non-polar solvent is a C5~C8 alkane, C1~C3 haloalkane, C2~C6 ether, or C2~C6 ester for the prevention or treatment of liver dysfunction or liver disease, characterized in that the pharmaceutical composition.
A pharmaceutical composition for preventing or treating liver dysfunction or liver disease comprising capsanthin as an active ingredient.
A health functional food composition for liver protection or liver function improvement comprising paprika extract as an active ingredient.
8. The method of claim 7,
A health functional food composition for liver protection or liver function improvement comprising capsanthin as an active ingredient.

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