JP5969529B2 - Anti-inflammatory agent - Google Patents

Description

The present invention relates to an anti-inflammatory agent containing a kuzu flower treatment product as an active ingredient. The present invention also relates to an oral composition using the anti-inflammatory agent.

Inflammation is a life-supporting reaction mechanism that protects the body from infection and damage. However, acute or chronic inflammation can cause tissue and cell damage and can be a potential source of various diseases.

Kuzu is a legume plant, and its roots have long been used as a raw material for Japanese sweets as kuzu starch. The roots and flowers of kuzu are called kuzu roots and kuzu flowers, respectively, and are used as herbal medicines for cold symptoms such as fever and cold. In particular, isoflavonoids contained in Kuzuka are known to have a hangover prevention effect (see Patent Document 1). Moreover, the blood-flow improving agent which uses a Kuzuhana processed material as an active ingredient has been reported until now (refer patent document 2).

JP 2000-7694 A JP 2006-249071 A

Patent Documents 1 and 2 suggest that isoflavonoids in kuzuka have a hangover prevention effect, and that the kuzuka processed product has a blood flow improving action. However, there is no description in Patent Documents 1 and 2 regarding the inhibitory effect of inflammation in relation to components in kuzuka and processed kuzuka.

Therefore, an object of the present invention is to provide an anti-inflammatory agent having an effect of suppressing inflammation.

As a result of intensive studies on the above problems, the present inventor has found that the processed kuzuka product has an action of suppressing inflammation and succeeded in producing an anti-inflammatory agent containing the processed kuzuka product. The present invention is a completed invention based on this success example.

Therefore, according to the present invention, there is provided an anti-inflammatory agent comprising a processed kuzuka product as an active ingredient.

According to another aspect of the present invention, or as another embodiment of the present invention, there is provided an oral composition containing the anti-inflammatory agent of the present invention, or comprising the anti-inflammatory agent in food or drink. .

The anti-inflammatory agent of the present invention can be expected to reduce the risk associated with the inflammatory reaction and improve the inflammation by suppressing the inflammation. In particular, an inflammatory cell infiltration suppressing effect, a Gr-1 positive cell infiltration suppressing effect, a CD4 positive cell infiltration suppressing effect, and an NK1.1 positive cell suppressing effect can be expected.

The anti-inflammatory agent of this invention can be mix | blended with an oral composition, or it can take the form of an oral composition with another additive or it mix | blends with the existing food-drinks.

It is the photograph figure which showed the hematoxylin eosin dyeing | staining image of a test substance administration group and a control group. It is the photograph figure which showed the immuno-staining image of the anti-Gr-1 of a test substance administration group and a control group. It is the photograph figure which showed the immuno-staining image of the anti-CD4 of a test substance administration group and a control group. It is the photograph figure which showed the immuno-staining image of the anti-NK1.1 of a test substance administration group and a control group.

Details of the present invention will be described below.
The anti-inflammatory agent of this invention contains the kuzuka processed material obtained by processing kuzuka as an active ingredient.

Kuzuka is the flower part of the Kuzu plant. The kuzu plant is a perennial plant belonging to the genus Leguminosae as is generally known, and is known to be distributed in Japan, China, Taiwan, Southeast Asia and the like. The kind of kuzu plant used in the present invention is not particularly limited, and examples thereof include Pueraria thomsonii, Pueraria robota, and Pueraria thumbergiana. It is preferable to use Pueraria thomsonii. The kuzuka, which is the raw material of the kuzuka processed product that is the active ingredient of the anti-inflammatory agent of the present invention, may be kuzuka collected at any stage of flowering, but from the viewpoint of the anti-inflammatory effect, It is preferable that they are Kuzuka collected at the stage of cocoon.

The kuzu flower processed product includes kuzu flower itself in addition to the kuzu flower processed. There are no particular limitations on the means for treating kuzuhana, and for example, physical or chemical treatment that can be usually employed when processing flower parts of plants such as shredding, crushing, grinding, drying, heating, and extraction. That's fine. A preferable embodiment of the processed kuzuka product is a dried kuzuka product or a kuzuka extract containing at least one component selected from the group consisting of isoflavonoids, saponins, and glycosides thereof.

The dried kuzu flower is obtained by drying kuzu flowers, and examples thereof include dried kuzu flowers themselves, dried powder obtained by drying kuzu flowers themselves and then crushing them. There are no particular restrictions on the means of drying the kuzuka to obtain the katsuka dried product. For example, the kuzuka dried product obtained by drying the kuzuka collected at the stage of the koji before fully opening it by sun drying or hot air drying. Can be obtained. The degree of drying may be a degree until it is confirmed that the water content of Kuzuka is sufficiently reduced. For example, it is preferably a degree until the water content becomes 10 wt% or less. . Moreover, as needed, Katsuhana dried material can be made into the form of a powder by grind | pulverizing.

In the case of obtaining a dried kuzuka powder, the powdering method includes, for example, a method of pulverizing and pulverizing dried kuzuka using a ball mill, hammer mill, roller mill, etc., which are commonly used by those skilled in the art. However, it is not limited to these. The order of drying and pulverization can be changed, and the kuzuka before drying can be pulverized in advance with a mass collider, a slicer, a comitolol, etc., and the pulverized product can be dried to obtain a dried kuzuka powder.

The kuzuhana extract is not particularly limited as long as the components contained in kuzuka are extracted, and the extract obtained by squeezing kuzuka or using kuzuka and a solvent is extracted. Liquid and the like. The kuzu flower extract may be a product obtained by concentrating the juice or the extract, for example, a liquid, paste, powder, fine particle, granule, pellet, tablet, or other solid form. May be. In any case, only the kuzu flower extract may be used, or in the case of liquid or paste, for example, it may be mixed with a solvent or the like. In the case of a solid, it may be mixed with an excipient, and further molded with an excipient or a binder. In the present invention, liquid, powder, fine granules, and granules are preferred, powder, fine granules, and granules are more preferred, and powder is particularly preferred because of ease of mixing with food and drink.

When the Kuzuhana extract is obtained in the form of an extract, it can be obtained by a solvent extraction means using a generally known plant. For example, a kuzu flower extract can be obtained by adding kuzu flower in a solvent and appropriately heating or stirring. Moreover, it can be set as the kuzu flower extract which consists of a liquid component except solid content using the solid-liquid separation means normally known, such as centrifugation and filtration. In addition, as the kuzu flower used as the raw material of the kuzu flower extract, katsuhana before and after drying can be used. From the viewpoint of extraction efficiency, for example, the kuzu flower dry product is preferable, More preferably, it is a powder.

Examples of the solvent used when obtaining the kuzuhana extract include water, hot water, an organic solvent, a water-containing organic solvent, and the like. In addition, the organic solvent is not particularly limited as long as it is an organic solvent that is usually used for the extraction treatment. For example, methanol, ethanol, n-propanol, n-butanol, acetone, hexane, cyclohexane, propylene glycol, ethyl methyl ketone, Examples include glycerin, methyl acetate, ethyl acetate, diethyl ether, dichloromethane, edible oils and fats, 1,1,1,2-tetrafluoroethane, 1,1,2-trichloroethene, and the like. Among these, water, hot water or a polar organic solvent is preferable, water, hot water, ethanol, n-butanol, methanol, acetone, propylene glycol or ethyl acetate is more preferable, and water, hot water or ethanol is more preferable.

When obtaining a kuzu flower extract, it can be extracted without heating, but it is preferable to warm from the viewpoint of extraction efficiency. Examples of the warm extraction means include a warm extraction method such as heating reflux, a supercritical extraction method, and the like. In some cases, a means for heating by pressurization can be employed. The extraction temperature in the warm extraction is not particularly limited as long as it is a temperature below the boiling point of the solvent used. Although extraction temperature changes also with the solvent to be used, it is 4 to 150 degreeC generally. In order to prevent the solvent used for extraction from volatilizing, the lower limit value of the heating temperature is, for example, 30 ° C. or more, preferably 50 ° C. or more, and the upper limit value of the heating temperature is, for example, 150 ° C. or less, preferably 130 It is better to set it below ℃.

What is necessary is just to set extraction time suitably according to extraction temperature etc., for example, it is tens of minutes to dozens of hours, and can be 30 minutes-48 hours depending on heating conditions and stirring conditions. In addition, when extracting without heating or when extracting at less than 50 degreeC, extraction time can be made into 6 hours-48 hours, for example, when heating at 50 degreeC or more, for example, extraction time 30 minutes to 24 hours. The extraction time, that is, the time from the start to the end of the extraction depends on various conditions. For example, the concentration of soluble components is measured over time, and the extraction ends when the concentration reaches a plateau at the maximum concentration. It can be time.

The kuzu flower extract may be obtained by subjecting the extract obtained through the extraction operation to concentration or drying such as vacuum concentration or freeze drying in order to remove an organic solvent, for example.

The Kuzuhana extract may be an extract purified using a column or a concentrator such as a synthetic adsorbent such as Diaion HP20, Sephabies SP825L, Amberlite XAD4, or MCIgelCHP20P, or a dextran resin such as Sephadex LH-20. .

As already known, the processed kuzuhana product exhibits physiological activities such as hangover prevention and blood flow improvement. Surprisingly, as shown in the examples described later, the processed kuzuka product exhibits an inhibitory action on the proliferation or induction of cells involved in the inflammatory reaction in the liver, and an inhibitory action on infiltration of inflammatory cells into the liver. Based on these, it has an anti-inflammatory effect. More specifically, the processed kuzuka product has a remarkable improvement effect on inflammation of the liver parenchyma, particularly in the liver. Furthermore, the processed Kuzuka product has an effect of improving the infiltration of Gr-1 positive cells, CD4 positive cells, and NK1.1 positive cells among cells involved in the inflammatory reaction in the liver. Therefore, the anti-inflammatory agent of the present invention can suppress, reduce or alleviate inflammation in mammals by containing the processed kuzuka as an active ingredient. Moreover, another aspect of the present invention includes a hepatic parenchymal inflammation inhibitor, an inflammatory cell infiltration inhibitor, a Gr-1 positive cell infiltration inhibitor, a CD4 positive cell infiltration inhibitor, and NK1, each containing a processed kuzuka product as an active ingredient. .1 Positive cell infiltration inhibitor.

Furthermore, the anti-inflammatory agent of the present invention has a probability of preventing inflammation by acting not only on the inflammation that has already occurred but also acting on a site where inflammation may occur. In particular, as shown in the examples described later, the processed Kuzuka product has an effect of improving inflammation in the liver and an effect of preventing a disease that develops due to progression of inflammation, and therefore, as another aspect of the present invention. It is possible to provide a preventive agent for hepatitis containing a processed kuzuka product as an active ingredient, preferably a non-alcoholic hepatitis preventive agent containing a processed kuzuka product as an active ingredient.

The amount of the kuzuhana treatment product is not particularly limited as long as it is an effective amount capable of exhibiting an anti-inflammatory effect. When the kuzu flower processed product is a kuzu flower extract, the blending amount of the kuzu flower extract can be set such that the lower limit value is 10% or more in terms of dry mass as the daily intake amount for adults. . Further, the upper limit value of the intake amount per day for an adult can be set to be, for example, 3,000 mg or less, preferably 1,000 mg or less in terms of dry mass.

When the kuzu flower processed product is a kuzu flower dried product, the blended amount of the kuzu flower dried product is set such that the lower limit value is the dry mass, for example, 0.1 g or more as the daily intake amount for adults. The upper limit of the intake amount per day for an adult can be set, for example, to be 30 g or less, preferably 10 g or less.

As another aspect of the present invention, there is provided an oral composition comprising the anti-inflammatory agent of the present invention or comprising the anti-inflammatory agent of the present invention blended in a food or drink.

The compounding amount of the processed kuzuka product in the oral composition of the present invention can be appropriately set depending on the form and dosage form, and is not particularly limited. When the processed kuzuka extract is a kuzuka extract, the blending amount of the kuzuka extract is 100 parts by mass of the oral composition, and the lower limit value of the kuzuka extract is a dry mass, for example, 0.0001. The upper limit value of the Kuzuhana extract can be set to dry mass, for example, 50 parts by mass or less, preferably 30 parts by mass or less. . When the kuzu flower treatment product is a kuzu flower dry product, the blending amount of the kuzu flower dry product is 100 parts by mass of the oral composition, and the lower limit value of the kuzu flower dry product is a dry mass, for example, 0.01 The upper limit value of the dried Kuzuka product can be set to dry mass, for example, 80 parts by mass or less, preferably 50 parts by mass or less. .

If necessary, the oral composition of the present invention is added with excipients, extenders, binders, thickeners, emulsifiers, coloring agents, fragrances, other food and beverage ingredients, seasonings, pharmaceutical ingredients, etc. May be. Furthermore, the oral composition containing the anti-inflammatory agent of the present invention can be formulated into capsules such as hard capsules and soft capsules, tablets, pills, etc. depending on the use, or powdered, granular, tea It can be formed into a shape that can be taken as a normal food or drink such as a shape, a tea bag shape, or a bowl shape, and can also be used as a liquid beverage. When ingesting the oral composition of the present invention, these forms can be taken as they are or dissolved in water, hot water, milk or the like according to taste. In addition, when the oral composition of the present invention is in the form of a powdered tea bag, it is preferable to drink after leaching the contained components in hot water or the like.

Examples of the raw material or food that can be blended in the oral composition of the present invention include royal jelly, propolis, vitamins (A, C, D, E, K, folic acid, pantothenic acid, biotin, derivatives thereof, etc. ), Minerals (iron, magnesium, calcium, zinc, etc.), selenium, α-lipoic acid, lecithin, polyphenols (flavonoids, derivatives thereof, etc.), carotenoids (lycopene, astaxanthin, zeaxanthin, lutein, etc.), xanthine derivatives (cafe) In), fatty acids, proteins (collagen, elastin, etc.), mucopolysaccharides (hyaluronic acid, etc.), amino sugars (glucosamine, acetylglucosamine, galactosamine, acetylgalactosamine, neuraminic acid, acetylneuraminic acid, hexosamine, salts thereof, etc. ) Gosacose (isomalto-oligosaccharides, cyclic oligosaccharides, etc.), sphingolipids and phospholipids and their derivatives (phosphatidylcholine, sphingomyelin, ceramide, etc.), sulfur-containing compounds (aryin, sepaene, taurine, glutathione, methylsulfonylmethane, etc.) ), Sugar alcohols, lignans (such as sesamin), plant and animal extracts containing these, root vegetables (turmeric, ginger, etc.), green leaves of gramineous plants such as wheat leaves, green leaves of cruciferous plants such as kale Although it is mentioned, it is not limited to these.

Examples of the seasoning include, but are not limited to, sweeteners such as granulated sugar, honey, and sorbit; alcohol; and acidulants such as citric acid, malic acid, and tartaric acid. Sugar solution, sugar alcohol, seasoning and the like can be added to enhance the sweetness of the oral composition of the present invention.

The oral composition of the present invention contains a physiologically active component such as a lipid absorption inhibitory component, a lipid metabolism promoting component, and a second anti-inflammatory component in addition to the processed Kuzuka product, thereby synergistic lipid accumulation. An inhibitory effect, a body fat reduction effect, an anti-inflammatory effect, etc. can be acquired.

Examples of the lipid absorption inhibitory component include components having an action to excrete bile acids such as chitosan and its derivatives, psyllium and proanthocyanidins, and components having a lipase inhibitory action such as gallotannin, loquat leaves and extracts thereof. However, it is not limited to these. In addition, for example, a plant extract containing a large amount of proanthocyanidins such as a pine bark extract can be used as the proanthocyanidins.

Examples of lipid metabolism promoting components include riboflavins, tea catechins, isomerized linoleic acid, caffeine, capsaicin, carnitine, coenzyme Q10, soybean peptide, branched amino acid, phosphatidylcholine, allyl sulfide compound, forskolin, bergenin , Quercetin, astilbine, hydroxycitric acid, and salts thereof, but are not limited thereto. The lipid metabolism promoting component may be these components or a plant-treated product containing these components, for example, treatment of tea, coleus foli, red pepper, soy, chili, buckwheat, garlic, onion, coffee, etc. The product can be used as a lipid metabolism promoting component.

Examples of the second anti-inflammatory component include, but are not limited to, catechins, allyl sulfide, capsaicin, curcumin, tranexamic acid, glycyrrhizic acid, pantothenic acid, bromelin and the like. The second anti-inflammatory component may be these components or a processed plant containing these components, for example, processed products such as tea, leek, garlic, leek, onion, chili, turmeric, licorice, It can be used as a second anti-inflammatory component.

In the oral composition of the present invention, a lipid absorption inhibiting component, a lipid metabolism promoting component and a second anti-inflammatory component are appropriately blended according to the purpose. For example, any one or two of these components may be blended, or all of these components may be blended. Moreover, two or more types of lipid absorption inhibiting components, lipid metabolism promoting components, or second anti-inflammatory components can be blended.

As specific examples of the oral composition of the present invention, green leaves such as wheat young leaves (for example, barley young leaves), kale, tomorrow leaves, and mulberry leaves, which have been eaten for health in recent years, are powdered and taken as beverages. As a so-called “aojiru”, using katsuhana processed product, it can be made into a more enjoyable aojiru than other aojiru, and further, it is blended with other aojiru ingredients that are difficult to ingest. It is also possible to make it easier to ingest other green juice ingredients. Furthermore, it can be used for beverages containing food and beverage ingredients and foods and beverages, for example, plant fermented juice, vegetable juice (for example, carrot juice), plant extract, fruit juice, etc. In addition to improving palatability, the beverage can be made functional or highly nutritious.

Although the processing form of the composition for oral use of this invention is not specifically limited, For example, soft drinks, carbonated drinks, nutritional drinks, fruit drinks, lactic acid drinks, and other beverages (including concentrated concentrates and powders for preparation of these drinks); Ice cream, sorbet, frozen yogurt, shaved ice and other frozen desserts; buckwheat noodles, udon, harusame, gyoza skin, cucumber skin, Chinese noodles, instant noodles and other noodles; rice cakes, chewing gum, candy, gum, chocolate, tablet confectionery, snacks , Biscuits, jelly, jam, cream, baked confectionery, etc .; fish and livestock processed foods such as kamaboko, ham, sausage; dairy products such as processed milk and fermented milk; salad oil, tempura oil, margarine, mayonnaise, shortening, Fats and oils such as whipped cream and dressing; processed foods; sauces, sauces, etc. Seasonings; soup, stew, salad, prepared foods, pickles, and the like.

As another aspect of the present invention, there is provided a pharmaceutical composition for preventing or treating hepatitis through suppression of inflammatory cell infiltration, comprising a processed kuzuka product as an active ingredient. The pharmaceutical composition of the present invention can prevent and / or treat hepatitis such as non-alcoholic hepatitis by targeting the processed Kuzuka product to Gr-1 positive cells. The pharmaceutical composition of the present invention can be produced by appropriately blending a kuzu flower treatment product with a pharmaceutical raw material for a pharmaceutical preparation. The administration method of the pharmaceutical composition of the present invention is not particularly limited and may be either oral administration or parenteral administration, but oral administration is preferred.

Hereinafter, the present invention will be described in more detail with reference to examples. However, the present invention is not limited to these examples, and the present invention can take various modes as long as the problems of the present invention can be solved. .

[1. Evaluation of usefulness of processed kuzuhana]
As a kuzu flower processed product, the flower part of kuzu (Pueraria thomsonii) was extracted with hot water, and dried kuzu flower extract powder was used. Compare the non-alcoholic hepatitis model mouse group (test substance administration group) bred with a mixed diet in which Kuzunohana extract powder is mixed with a high-fat diet and a model mouse group (control group) bred only with a high-fat diet Therefore, the usefulness of Kuzunohana extract powder in model mice was evaluated.

In the test substance administration group, Kuzunohana extract powder (Toyo Shinyaku Co., Ltd.) is mixed with solid feed High Fat Diet 32 (radiation sterilization, Nippon Claire Co., Ltd.) at a concentration of 50 g / kg (5 wt%) for model mice. In the control group, only the solid feed High Fat Diet 32 was ingested in the control group.

The model mouse is a model mouse showing pathological findings similar to the progression and prognosis of human liver disease that develops hepatitis at the age of 8 weeks, liver fibrosis at the age of 9 weeks, and then liver cancer at the age of 20 weeks. Model mice were streptozotocin (Sigma Aldrich Japan Co., Ltd.) 10 mg of male SPF mice (C57BL16J, Charles River Japan Co., Ltd.) at 2 days of age in physiological saline (Japanese Pharmacopoeia, Otsuka Pharmaceutical Factory Co., Ltd.). It was prepared by administering once to the back of the back at 20 μL / head (200 μg / head), feeding the mother to 4 weeks of age, and then feeding a high fat diet. However, the solid feed CE-2 (radiation sterilization, CLEA Japan, Inc.) was freely ingested by both mothers and infants until weaning.

The model mice were weighed on the day before the start date of administration, and 18 mice were extracted by weight stratification random sampling, and the test substance administration group and the control group were divided into 2 groups (9 Animals / group). For each group, 3 animals were raised per cage. The administration period was 28 days from 4 weeks of age. The test animals in each group after the end of the administration period were laparotomized under diethyl ether anesthesia to obtain livers.

<Inflammation assessment in liver parenchyma>
The center of the test animal's liver was immersed in a Buan fixative (Sigma Aldrich Japan Co., Ltd.), fixed at room temperature for 24 hours, and then paraffin sections. Using paraffin sections, hematoxylin and eosin staining was performed according to a conventional method. In addition, according to the report of Kleiner et al. (Kleiner DE et al., Hepatology, 2005; 41: 1313), the inflammation in the liver parenchyma was evaluated according to the contents of Table 1. A hematoxylin-eosin stained image is shown in FIG. 1, and inflammation evaluation results in the liver parenchyma are shown in Table 2.

From FIG. 1, inflammatory cell infiltration images including lymphocytes and neutrophils were observed in the control group. In contrast, a decrease in inflammatory cell infiltration was observed in the test substance-administered group compared to the control group.

From Table 2, it was found that inflammation in the liver parenchyma showed a marked decrease in the test substance administration group.

<Evaluation of Gr-1 positive cells, CD4 positive cells and NK1.1 positive cells>
The center of the liver of the test animal was immersed in a neutral formalin solution (Wako Pure Chemical Industries, Ltd.), fixed at room temperature for 24 hours, and then replaced with sucrose. C. T. T. et al. After embedding in a compound dish filled with compound, it was immediately frozen in liquid nitrogen. The frozen section was subjected to anti-Gr-1 immunostaining or anti-CD4 immunostaining according to a conventional method, and photographs of 5 fields per section with a CCD camera (Leica Microsystems) at a 200-fold field centered on the central vein. I took a picture. Based on the photographed image, the number of Gr-1 positive cells and the number of CD4 positive cells were calculated. In addition, paraffin sections were deparaffinized and hydrophilized, and then stained according to the package insert of anti-NK1.1 antibody (BDPharmingen) and EnVision FLEX Mini Kit, High pH Kit (Dako Japan), with Aquatex (Merck). Encapsulated and used for analysis. Photographs of 5 fields per section were taken with a CCD camera in a 200 times field of view centered on the central vein. The number of NK1.1 positive cells was calculated based on the photographed image. The immunostaining images of anti-Gr-1, anti-CD4 and anti-NK1.1 are shown in FIGS. In addition, Table 3 shows the number of positive cells of these immunostaining. The number of positive cells is shown as an average value.

From FIG. 2, in the control group, infiltration of Gr-1 positive cells around the central vein was observed. Compared with the control group, reduction of Gr-1 positive cell infiltration was observed in the test substance administration group. From Table 3, the number of Gr-1 positive cells around the central vein showed a lower value in the test substance administration group compared to the control group.

From FIG. 3, in the control group, infiltration of CD4 positive cells around the central vein was observed. Compared to the control group, the test substance-administered group showed a tendency to reduce CD4 positive cell infiltration. From Table 3, the number of CD4 positive cells around the central vein showed a lower value in the test substance administration group than in the control group.

From FIG. 4, in the control group, infiltration of NK1.1 positive cells around the central vein was observed. From Table 3, the number of NK1.1 positive cells around the central vein was lower in the test substance administration group than in the control group.

From the results of FIGS. 2 to 4 and Table 3, in the test substance administration group, a decrease in the number of Gr-1 positive cells, the number of CD4 positive cells and the number of NK1.1 positive cells was observed as compared with the control group. From these results, it was shown that Kuzunohana extract powder has an inhibitory effect on proliferation or induction of cells involved in an inflammatory reaction or an inhibitory effect on infiltration of inflammatory cells. In particular, it has been shown to have an inhibitory effect on the proliferation or induction of cells that express Gr-1, CD4 and NK1.1, or an inhibitory effect on inflammatory cell infiltration.

[2. Example of oral composition containing processed kuzuhana]
(1) Formulation Example 1: Water was added to the beverage Kuzuka extract and stirred to dissolve the Kuzuka extract. Thereafter, filtration was performed to remove impurities. The obtained liquid was sterilized and filled to obtain a beverage having the composition shown in Table 4.

(2) Formulation Example 2: Green tea leaves were added to hot water at a beverage of 80 ° C. to extract green tea, and then cooled to room temperature. Green tea leaves were removed by filtration to obtain a green tea extract. Next, a solution obtained by adding water and dissolving the kuzuhana extract was added to the green tea extract obtained earlier. Next, what added and dissolved water to sodium L-ascorbate was added to the green tea extract. Next, a solution obtained by adding sodium bicarbonate to hot water at about 70 ° C. and dissolving it was added to the green tea extract. The obtained liquid was sterilized and filled to obtain beverages shown in Table 5.

(3) Formulation Example 3: Granules Granules were produced using the raw materials shown in Table 6.

(4) Formulation Example 4: Tablets Tablets were produced using the raw materials shown in Table 7.

The anti-inflammatory agent of the present invention reduces the risk of developing inflammation and improves symptoms, in particular, suppresses inflammatory cell infiltration, suppresses Gr-1 positive cell infiltration, suppresses CD4 positive cell infiltration, and suppresses NK1.1 positive cells. Has an effect. By using these for food and drink, cosmetics, pharmaceuticals, etc., it contributes to the health and welfare of many adults.

Claims (1)

A Gr-1 positive cell infiltration inhibitor, a CD4 positive cell infiltration inhibitor or an NK1.1 positive cell infiltration inhibitor for improving non-alcoholic hepatitis, comprising a hot water extract of Kuzuhana as an active ingredient.