JP4873605B2 - A composition having an angiogenesis-inhibiting action comprising a cereal-derived ingredient as an active ingredient - Google Patents

Description

  The present invention relates to a composition having an angiogenesis-inhibiting action containing a cereal-derived ingredient as an active ingredient. More specifically, the present invention relates to a composition for treating or preventing a disease that should inhibit angiogenesis, which comprises a substance contained in barley, preferably a barley brown wheat ethyl alcohol extract fraction, or a barley brown wheat alkali extract fraction as an active ingredient. Product, preferably a composition in the form of food material, food and drink, feed and the like.

  Cancer has been the leading cause of death in Japan since 1981. Among the three major causes of death, only cancer has consistently increased and the number of deaths continues to increase. According to the Ministry of Health, Labor and Welfare's demographic statistics, out of 97,331 deaths in 2001, 300,658 died from cancer, and one in three died from cancer. It will be. For such diseases, the main treatment currently performed in hospitals is symptomatic treatment in which cancer cells are directly attacked by various therapies such as drugs, chemistry, and physics. Not only that, normal cells are damaged, and there is a problem that patients often die as a result of a decrease in immunity and natural healing power. With this background, the demand for safe treatments with few side effects is increasing day by day, and more emphasis is placed on prevention than disease treatment.

  In recent years, the application of angiogenesis inhibition as a safe cancer treatment has attracted attention. By producing angiogenesis-promoting substances, cancer cells have the property of spreading blood and feeding nutrients and oxygen to their cells, supplying enough blood, and repeating explosive growth. However, cancer treatment applying an angiogenesis inhibitory action is to prevent the proliferation of cancer cells by blocking the blood pathway to the cancer cells. That is, to put it simply, cancer cells are attacked.

  In recent years, it has been reported that the action of inhibiting angiogenesis has the effect of preventing and safely treating not only cancer but also rheumatoid arthritis, diabetes, heart disease and other various diseases (Non-patent Document 1 ~ 3) Early provision of a substance having an anti-angiogenic action is strongly demanded.

  Regarding an active ingredient derived from a natural product having an angiogenesis inhibitory action, Patent Document 1 discloses an angiogenesis inhibitor, a cell growth inhibitor, and a lumen formation inhibitor containing tocotrienol obtained from palm skin and seeds as an active ingredient. Agents and FGF inhibitors and foods or food additives are described, and Patent Document 2 describes a food composition for inhibiting angiogenesis including shiitake mycelium extract. Patent Documents 3 and 4 describe that a novel compound obtained by culturing a filamentous fungus and obtained from the culture solution has an angiogenesis inhibitory effect.

  By the way, barley, a gramineous plant, has been indispensable for humankind since prehistoric times, and has been loved as a healthy food, as described in old Japanese medical books. Various studies have been conducted on the physiologically active function of barley or barley fermented with microorganisms.

  Patent Document 5 discloses that an extract obtained from a crushed fraction of barley is extracted with an aqueous solvent, so that an extract mainly from the husk fraction is useful for bioactivity, that is, immune enhancement, blood pressure lowering, and blood flow improvement. Functional food materials that have physiological activity such as action, angiotensin I converting enzyme inhibitory action, and antibacterial action are described. However, this invention is an extract extracted from the bark grain fraction, its active ingredient is a readily water-soluble substance, has a molecular weight of 500,000 or less, the main component is a molecular weight of 100,000 or less, a protein content of 3 to 30%, It is rich in water-soluble ferulic acid and p-coumaric acid.

  As an invention using a barley shochu distillation residue as a by-product in the production of shochu using barley as a raw material, Patent Document 6 discloses a liquid component obtained by solid-liquid separation of the barley shochu distillation residue, and an alkali is added to the liquid component. To add an alkali-soluble fraction, neutralize the alkali-soluble fraction with an acid to obtain a neutral soluble fraction, and add the ethanol to the neutral soluble fraction. It is described that an ethanol-insoluble fraction containing acid, protein, and hemicellulose has a fatty liver inhibitory action, and Patent Document 7 obtains a liquid component by solid-liquid separation of a barley shochu distillation residue, It is described that an organic solvent-insoluble fraction collected by adding an organic solvent to the liquid component has an inhibitory effect on leukemia cell growth. Patent Document 8 discloses from a barley shochu distillation residue, Patent Document Obtained in the same way as 7. The organic solvent-insoluble fraction, it is described that the activation of natural killer cells.

  Patent Document 9 includes a non-adsorbed fraction obtained by solid-liquid separation of a barley shochu distillation residue and applying the liquid to a synthetic adsorbent, and the non-adsorbed fraction has an average chain. A plurality of peptides having a length of 3.0 to 5.0 are contained, and these peptides have an amino acid composition of glutamic acid 24 to 38%, glycine 4 to 20%, aspartic acid 5 to 10%, proline 4 to 9%, and serine 4 to 8%, and has a suppressive action and curative action on alcoholic liver damage and has an excellent taste. Products and methods for their production are described. Patent Document 10 describes a pharmaceutical composition in which the composition obtained in the same manner as Patent Document 9 has an onset suppressing action and a healing action against alcoholic liver injury, and a method for producing the same.

  Further, in Patent Document 11, a barley shochu distillation residue is subjected to solid-liquid separation to obtain a liquid component, which is subjected to an ion exchange treatment to obtain an ion-exchange resin non-adsorbed fraction. It is described that the organic solvent-insoluble fraction obtained by subjecting the adsorbed fraction to ultrafiltration treatment to obtain a concentrated liquid and adding an organic solvent to the concentrated liquid has an antioxidant action.

Eur.J.Cancer., 32A, 2534-2539 (1996) Nature Med., 1, 27-33 (1995) Immunity., 12, 121 (2000) JP 2002-308768 A JP 2004-196791 A JP 2003-183249 A JP 2004-262881 A JP 2002-371002 A Japanese Patent Laid-Open No. 2001-145472 JP 2003-73294 A JP 2003-73295 A Japanese Patent Laid-Open No. 2004-112 Japanese Patent Laid-Open No. 2004-2266 Japanese Patent Laid-Open No. 2004-238452

  As described above, barley and fermented barley have been confirmed to have various physiological activities, but the angiogenesis inhibitory action is not included in the physiological activities. It has not been known so far.

  The present invention has no problem in safety, is inexpensive and relatively easily available material, preferably from barley, without complicated purification steps, by a simple processing method suitable for actual production on a factory scale, Providing a composition having an excellent angiogenesis inhibitory effect, preferably a composition for treating or preventing a disease that should inhibit angiogenesis, more specifically, a food additive, a food material, a food and drink, and a pharmaceutical product -It aims at providing the thing of the form chosen from the group which consists of a quasi-drug and feed.

  As a result of intensive studies to solve the above problems, the present inventors have found that an excellent angiogenesis inhibitory action exists in cereal-derived components, particularly barley-derived components, and have made an invention. In the present invention, the barley brown barley ethyl alcohol extract fraction and the barley brown bark alkali extract fraction have a significant angiogenesis inhibitory action, thereby providing a composition having angiogenesis inhibitory activity with fewer side effects. can do.

That is, the gist of the present invention is the composition for inhibiting angiogenesis of the following (1) and (2 ).
(1) A composition for inhibiting angiogenesis, characterized in that an ingredient selected from the group consisting of a barley brown barley ethyl alcohol extract fraction and a barley brown barley alkali extract fraction is used as an active ingredient of an angiogenesis inhibitory action.
(2) The composition according to (1) above, wherein the composition for inhibiting angiogenesis is a composition for treating or preventing a disease caused by abnormal angiogenesis in a tumor or cancer, chronic inflammation or retinopathy A composition for inhibiting angiogenesis .

  The present invention has no problem in safety, is inexpensive and relatively easily available material (barley brown barley), without a complicated purification process, by a simple processing method suitable for actual production on a factory scale, A composition having an angiogenesis inhibitory activity with few side effects, preferably a composition for treating or preventing a disease that should inhibit angiogenesis, more specifically, a food additive, a food material, a food or drink, a pharmaceutical product / medicine The thing of the form chosen from the group which consists of a quasi-drug and a feed can be provided.

  The composition having angiogenesis inhibitory activity described in the present invention can be prepared from a plant of the family Gramineae such as barley, wheat, rye, oats, hard wheat and rice, but barley is preferably used. Barley may be either barley or bare barley, or may be either Nijo barley or Rojo barley. Colored barley with pigments deposited on the grain surface may also be used. The form of the grain is not particularly limited, such as the whole grain, epidermis, endosperm, etc., but it is preferable to use the whole grain such as brown wheat. In addition, processing such as roasting, milling, and pressure biasing may be added.

The above composition of the present invention has no problem in safety, and is produced from a cheap and relatively easily available material (Poaceae), preferably barley, on a factory scale without complicated purification steps. It can be expected to obtain an excellent angiogenesis inhibitory effect when applied to foods, drinks, pharmaceuticals, fertilizers, feeds and skin external preparations.
The composition of the present invention has an active ingredient derived from a natural product having an angiogenesis inhibitory action, and by applying angiogenesis inhibition based on the active ingredient, for example, leads to a safe cancer treatment method. Therefore, the action of inhibiting angiogenesis is a functional composition having an effect of preventing and safely treating not only cancer but also rheumatoid arthritis, diabetes, heart disease and other various diseases.
That is, the composition of the present invention is a composition for treating or preventing a disease that should inhibit angiogenesis. The disease that should inhibit angiogenesis is a target as long as it is a disease in which angiogenesis plays an important role in the pathogenesis. Thus, diseases that should inhibit angiogenesis are diseases caused by abnormal angiogenesis in tumors or cancer, chronic inflammation or retinopathy. More specifically, diseases that should inhibit angiogenesis include, for example, solid tumors, myelomas, hemangiomas and other tumors or cancers that occur in various tissues; rheumatoid arthritis, psoriasis, osteoarthritis, etc. Diseases such as, but not limited to, chronic inflammation; or retinopathy such as age-related macular degeneration, diabetic retinopathy, neovascular glaucoma; In the present invention, it is preferable to target various tumors or cancers as diseases for inhibiting angiogenesis.

  In order to examine the angiogenesis inhibitory activity of the composition of the present invention in vitro, vascular endothelial cells and fibroblasts are cultured under culture conditions in the presence of VEGF, an angiogenesis-inducing factor, as necessary. Thus, it is possible to confirm whether or not angiogenesis is suppressed by adding the composition of the present invention to the culture in which the growth state at the initial stage of tube formation is created by co-culture. Inhibition of angiogenesis can be performed, for example, by staining a lumen to examine whether or not the lumen formation is suppressed. As a kit for investigating the inhibitory effect of angiogenesis in vitro, an angiogenesis kit (manufactured by KURABO) can be used, and an anti-CD31 antibody or an anti-von Willebrand factor antibody can be used to stain a lumen. A luminal staining kit using an antibody (manufactured by KURABO) can be used.

  The composition of the present invention is characterized in that an ingredient derived from barley is used as an active ingredient for inhibiting angiogenesis. The substance exhibiting angiogenesis-inhibiting action contained in the barley-derived component is preferably a substance contained in the barley brown wheat ethanol extract fraction and the barley brown wheat alkali extract fraction.

  As a method of obtaining the barley brown barley ethanol extraction fraction, the barley brown barley was crushed with a mill and extracted with ethanol. The filtrate was filtered through a filter paper, the filtrate was concentrated under reduced pressure, ethanol was removed, and centrifugation was performed. And the method of obtaining the liquid part of a barley brown wheat ethanol extract is illustrated. As a method for obtaining a brown barley alkaline extract fraction, an aqueous alkaline solution is added to a barley brown barley crushed with a mill to obtain an extract, and the extract is neutralized with an acid, followed by filtration through filter paper. And a method for obtaining the liquid content of the barley brown barley alkaline extract.

The barley brown barley ethanol extract and / or barley brown bark alkali extract fraction is in a form selected from the group consisting of food additives, food ingredients, food and drink, pharmaceuticals / quasi drugs, and feed for inhibiting angiogenesis. Is. Utilizing the functionality of the composition, it has become possible to develop healthy foods and drinks, foods containing nutritional foods and drinks for patients, and feeds for domestic animals such as livestock, poultry and fish.
That is, the said food / beverage products are a functional food, a nutritional supplement, or a health food / beverage product for inhibiting angiogenesis. The feed is a feed for livestock, poultry and pets for inhibiting angiogenesis. Specifically, the food material containing the brown wheat ethanol extract described above can be used in any form of food form, beverage form or feed form.
In the case of using the above-described functionality of the composition for inhibiting angiogenesis of the present invention, the content is not particularly limited, but is appropriately adjusted depending on the degree of intended function, usage mode, usage amount, etc. For example, it is 0.001-100 mass%. The composition for inhibiting the angiogenesis can be used for the human body, other foods and drinks, pharmaceuticals, feeds and external preparations for skin. It can also be taken orally or applied to the skin. Can be incorporated into oral and parenteral products according to conventional methods and used in various fields such as seasonings, food additives, food ingredients, food and drink, health food and drink, topical skin preparations, pharmaceuticals and feed Can do. For example, when blended with food or drink, food or drink for treating or preventing a disease that should inhibit angiogenesis can be provided. From the effect of prevention, it can be expected to be used as health food, nutritional food, etc. In addition, it can be used for livestock and / or fish feed and feed. By using it for the human body and other foods and drinks, pharmaceuticals, fertilizers, feeds and external preparations for skin, it is possible to obtain an effect of treating or preventing a disease that should inhibit angiogenesis.
Furthermore, it can be easily obtained from barley brown barley, which is preferable from the viewpoint of cost and effective utilization of resources.

When the composition of the present invention is used for food, it can be prepared as it is, in a form diluted with oil, a milk form meal, or a form to which a carrier generally used in the food industry is added. Also good.
In the form of an emulsion, for example, a composition is added to the oil phase, and liquid fats such as glycerin fatty acid ester, sorbitan fatty acid ester, sucrose fatty acid ester, glycerol, dextrin, rapeseed oil, soybean oil, corn oil, etc. L-ascorbic acid or its ester or salt, for example, gum such as locust bean gum, gum arabic or gelatin, for example, flavonoids such as hesperidin, rutin, quercetin, catechin, thianidine or polyphenols or the like It can be prepared by adding a mixture and emulsifying.

  The form of the beverage is a non-alcoholic beverage or an alcoholic beverage. Non-alcoholic beverages include, for example, non-carbonated beverages such as carbonated beverages, fruit juice beverages, and nectar beverages, soft drinks, sports beverages, tea, coffee, cocoa, and the like, and in the form of alcoholic beverages spirits, liqueurs, chuhai, The form of general foods, such as fruit liquor, barley liquor, Happoshu, and medicinal liquor, can be mentioned.

  Specific examples of food and drink include the following. Pastry (pudding, jelly, gummy candy, candy, drop, caramel, chewing gum, chocolate, pastry, butter cream, custard cream, cream puff, hot cake, bread, potato chips, french fries, popcorn, biscuits, crackers, pie, sponge Cakes, castella, waffles, cakes, donuts, biscuits, cookies, rice crackers, rice crackers, rice cakes, manju, candy, etc., dried noodle products (macaroni, pasta), egg products (mayonnaise, fresh cream), beverages (functional beverages, Lactic acid beverages, lactic acid bacteria beverages, concentrated milk beverages, fruit juice beverages, fruitless beverages, pulp beverages, transparent carbonated beverages, carbonated beverages with fruit juice, fruit colored carbonated beverages), luxury products (green tea, tea, instant coffee, cocoa, canned Coffee Milk), dairy products (ice cream, yogurt, coffee milk, butter, butter sauce, cheese, fermented milk, processed milk), pastes (marmalade, jam, flower paste, peanut paste, fruit paste, fruit syrup) , Livestock products (ham, sausage, bacon, dry sausage, beef jerky, lard), seafood products (fish meat ham, fish sausage, salmon, chikuwa, hampen, dried fish, bonito, bonito, boiled, sea urchin Salted fish, plums, dried fish, shellfish, salmon products such as salmon), boiled fish (small fish, shellfish, wild vegetables, salmon, kelp), curry (instant curry, retort curry, canned curry), seasoning (Miso, powdered miso, soy sauce, powdered soy sauce, moromi, fish sauce, sauce, ketchup, oyster sauce, solid bouillon List of grilled meat sauce, curry roux, stew sauce, soup sauce, dashi stock, paste, instant soup, sprinkle, dressing, salad oil), fried products (fried food, fried sweets, instant ramen), soy milk, margarine, shortening, etc. be able to.

  The said food and drink can be processed and manufactured by mix | blending a composition with the raw material of a general food according to a conventional method.

  Although the compounding quantity of the composition to the said food-drinks changes with forms of food and is not specifically limited, Usually, 0.001 to 20% is preferable.

  The above food and drink can also be used as functional foods, nutritional supplements or health foods. The form is not particularly limited, and examples of food production include milk proteins with high amino acid balance, soy protein, and proteins such as egg albumin, degradation products thereof, and egg white oligos. In addition to peptides, soybean hydrolysates, and the like, mixtures of amino acids alone can be used according to conventional methods. It can also be used in the form of a soft capsule, a tablet or the like.

  Examples of dietary supplements or functional foods include liquid foods, semi-digested nutritional foods, ingredient nutritional foods, drinks, capsules, and sucrose containing sugars, fats, trace elements, vitamins, emulsifiers, and fragrances. Processing forms such as enteral nutrients can be mentioned. In the above-mentioned various foods, for example, foods and drinks such as sports drinks and nutritional drinks are further supplemented with nutritional additives such as amino acids, vitamins and minerals, sweeteners, spices and fragrances to improve nutritional balance and flavor. , Pigments and the like can also be blended.

  In order to stabilize the composition of the present invention, an antioxidant such as tocopherol, L-ascorbic acid, BHA, rosemary extract and the like can be used in combination according to a conventional method.

The composition of the present invention can be applied to feed for livestock, poultry and pets. For example, it can mix | blend with livestock feeds, such as dry dog food, dry cat food, wet dog food, wet cat food, semi-moist dock food, poultry feed, cattle, and pigs. The feed itself can be prepared according to a conventional method.
These therapeutic agents and prophylactic agents include non-human animals, for example, domestic mammals such as cattle, horses, pigs and sheep, poultry such as chickens, quails and ostriches, pets such as reptiles, birds and small mammals, It can also be used for farmed fish.

  Although the preparation method of each composition which uses barley brown barley as a material, and the angiogenesis inhibitory effect are demonstrated below, the scope of the present invention is not limited to these illustrations.

  Details of the invention are given in the examples. The present invention is not limited by these examples.

[Experiment 1]
Angiogenesis inhibition experiment <sample name>
As shown in Table 1.
A1, A2: Negative control
A3, A4: Positive control
B1-B3: Brown wheat ethanol extract fraction powder
C1-C3: Brown wheat alkali extract fraction powder

<Preparation method of sample used for angiogenesis inhibition experiment>
The sample used in this experiment has a balance with other experiments, and the powdered sample is redissolved and used in the experiment. However, there is no problem even if it is used in the experiment as it is in a liquid state.

[Brown ethanol extraction fraction powder]
1 L of 75% (v / v) ethanol was added to 100 g of barley brown barley crushed with a mill, and the mixture was stirred and extracted at room temperature for 6 hours. The extract was filtered through 4C filter paper manufactured by ADVANTEC, and the filtrate was concentrated under reduced pressure to remove ethanol. Subsequently, the mixture was centrifuged at 10,000 rpm for 10 min to obtain a liquid content of the barley brown wheat ethanol extract, and the extract was freeze-dried.

[Brown alkali extracted fraction powder]
1 L of a 2% Ca (OH) ₂ aqueous solution was added to 100 g of barley brown barley crushed with a mill, and the mixture was stirred and extracted at room temperature for 6 hours, and then the pH of the extract was adjusted to 7.0 using HCL. Subsequently, the mixture was filtered with 4C filter paper manufactured by ADVANTEC to obtain a liquid content of the barley brown barley alkaline extract, and the extract was freeze-dried.

<Preparation of experimental samples, experimental methods, and results>
1. Experimental sample
1-1 Sample preparation
1-1-1 For angiogenesis inhibition experiment Each sample is weighed 1000 μg, dissolved separately in 1 ml medium, sterilized by filtration (0.22 μm), diluted 10 times (3 times), and Table 1 (Vessels) A sample having a concentration of 10 μg / ml to 1000 μg / ml as shown in the Breakdown of Newborn Inhibitory Effect Evaluation Test Samples) was prepared. Similarly, negative control and positive control samples shown in Table 1 were prepared.
2. Experimental methods and results Human vascular endothelial cells and fibroblasts were co-cultured at the optimal concentration, and each sample (1-1-1, negative control, positive control) was added to those in the proliferative state at the initial stage of tube formation. Then, after culturing for 11 days (the medium containing the sample was changed after 4, 7, and 9 days), tube formation was stained with Mouseanti-human CD31 and Goat anti-mouse IgG AlkP Conjugate and observed under a microscope. The formed lumen-like network structure was evaluated for the angiogenesis inhibitory effect.
The obtained results are shown in Table 2 and FIGS. The effect of inhibiting angiogenesis was determined by taking photographs of vascular tissues as digital data and measuring the areas of several randomly selected blood vessel portions (black portions). That is, the smaller the numerical value in the AREA column in Table 2, the higher the effect of inhibiting angiogenesis.

  An obvious angiogenesis-inhibiting effect was observed in the extract of brown wheat ethanol.

Experiment 2:
Angiogenesis inhibition experiment <sample name>
As shown in Table 3.

Preparation method of samples (1) to (9) used in the angiogenesis inhibition experiment The sample used in this case has a balance with other experiments, and the powdered sample is redissolved and used in the experiment. There is no problem even if it is used in the experiment in the liquid state. In addition, when powdered as described below, there is also a product added with an equivalent amount of dextrin as an extractant. The dextrin content is weight percent concentration (W / W).

(1) [Brown ethanol extraction fraction powder]
See paragraph 0036 above.

(2) [Brown wheat alkali extract fraction powder]
See paragraph 0037 above.

[Preparation of experimental samples, experimental methods, and results]
1. Experimental sample
1-1 Sample preparation
1-1-1 For angiogenesis inhibition experiment Each sample is weighed in 1000μg, dissolved separately in 1ml medium, sterilized by filtration (0.22μm), diluted 10 times (3 times), from 10μg / ml A sample with a concentration of 1000 μg / ml was prepared.

2. Experimental methods and results Human vascular endothelial cells and fibroblasts were co-cultured at optimal concentrations, each sample was added to the proliferating state at the initial stage of lumen formation, and cultured for 11 days (samples after 4, 7 and 9 days) After the medium containing the medium was exchanged), tube formation was stained with Mouse anti-human CD31 and Goat anti-mouse IgG AlkP Conjugate and then observed under a microscope. As evaluation criteria, 10 ng / ml of VEGF-A that promotes tube formation, 50 μM of Suramin that inhibits tube formation were similarly added, and control was not added. The formed lumen-like network structure was evaluated for the angiogenesis inhibitory effect.
Method: Measured with a kit manufactured by Kurabo Industries. The lumen formation state (area, length, number of branches) at four points was observed. Using a system in which VEGF as an angiogenic factor and Suramin as an angiogenesis inhibitor coexist as a control, the luminal formation state in the presence of VEGF and each sample was compared.
(Comparison of angiogenesis inhibitory activity of Suramin and sample)
Sample addition concentration: 10, 100, 1000 μg / mL
(Suramin is all constant concentration; 50μM)
Results: The results obtained are shown in Table 3 (numerical data on the angiogenesis inhibitory effect) and FIG.

  From the results shown in Table 3 and FIG. 4, the barley ethanol extract significantly inhibited tube formation at all of 10 μg / ml, 100 μg / ml, and 1000 μg / ml, and 100 μg of the barley alkaline extract was completely luminal. Inhibited formation.

  The composition of the present invention is an active ingredient derived from barley, which is a gramineous plant that has been loved as a healthy food, such as cereals indispensable for human beings from prehistoric times, as described in old Japanese medical books, etc. Is applied to inhibit angiogenesis based on the above, and is highly available as a functional food material.

4 is a photomicrograph in place of a drawing for explaining a state of lumen formation using VEGF-A and Suramin 50 μM in Example 1. FIG. A1; VEGF-A, A2; VEGF-A, A3; Suramin, A4; Suramin It is a microphotograph which replaces the figure explaining the mode of lumen formation using the brown wheat ethanol extract of Example 1, and the drawing explaining the mode of lumen formation of a control cultured without addition. Addition amount of brown wheat ethanol extract B1: 10 μg, B2: 100 μg, B3: 1000 μg, B4; medium only It is a microscope picture instead of drawing explaining the mode of lumen formation using the brown wheat alkali extract of Example 1 and describing the mode of lumen formation of a control cultured without addition. Brown wheat alkali extract addition amount C1; 10μg, C4; medium only 2 is a drawing for explaining the results of an angiogenesis inhibition test of Example 2. FIG.

Claims (2)

  A composition for inhibiting angiogenesis, comprising an ingredient selected from the group consisting of a barley brown barley ethyl alcohol extract fraction and a barley brown barley alkali extract fraction as an active ingredient for angiogenesis inhibitory action. The composition for inhibiting angiogenesis is a composition for treating or preventing a disease caused by abnormal angiogenesis in a tumor or cancer, chronic inflammation or retinopathy. Composition to do .