JP2005263766A - Anti-ulcer composition - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide an anti-ulcer composition which is derived from an evening primrose and has high safeness and an excellent anti-ulcer action. <P>SOLUTION: The anti-ulcer composition contains a solvent extract of an evening primrose. The solvent extract is preferably one of evening primrose seeds; more preferably, one of defatted evening primrose seeds. The solvent extract is preferably a water-containing ethanol extract, more preferably a water-containing ethanol extract with an ethanol concentration of 40-90% (wt/wt). The anti-ulcer composition is used preferably as a material for food and drink or for drugs. <P>COPYRIGHT: (C)2005,JPO&NCIPI

Description

  The present invention relates to an anti-ulcer composition derived from evening primrose, and in particular, a drug, food and drink capable of treating or preventing gastrointestinal diseases caused by ammonia produced by the action of urease produced by Helicobacter pylori Etc.

  It is known that Helicobacter pylori (hereinafter referred to as Helicobacter pylori) is involved in diseases such as gastritis, gastric ulcer, and duodenal ulcer. H. pylori is a gram-negative microaerobic bacterium that produces ammonia by urease activity and neutralizes gastric acid. Ammonia produced in the stomach changes the properties of the mucous membrane and mucus of the stomach, causing the stomach wall to become irritated and cause inflammation.

  Conventionally, many compounds having an antiulcer action have been reported, but many of them have been chemically synthesized, and various side effects due to continuous use have been reported. For this reason, highly safe plant-derived anti-ulcer action materials have been researched and developed. For example, Patent Document 1 discloses agarose-derived agaropectin, carrageenan, alginic acid, etc. of seaweed, mucopolysaccharide hyaluronic acid, neutral polysaccharide. In addition, Patent Document 2 discloses an anti-ulcer action containing carnosic acid and carnosol contained in a large amount in Lamiaceae plants such as rosemary and sage as active ingredients. However, these materials are subject to evaluation in animal models using ethanol and hydrochloric acid, and are different from ulcers caused by ammonia caused by Helicobacter pylori.

Japanese Patent Laid-Open No. 6-48950 JP 2001-122777 A (P2001-122777A)

Under these circumstances, the present inventors conducted screening using a rat ammonia-induced ulcer model in order to find a material effective for ammonia-induced ulcers, and have come to focus on the evening primrose extract. As a result of various experiments, it has been found that an extract of evening primrose, especially an extract of evening primrose seeds, has an anti-ulcer action, and has completed the present invention.
An object of the present invention is to provide an anti-ulcer composition derived from evening primrose having excellent anti-ulcer activity and high safety.
Another object of the present invention is to provide a food and drink and a medicine containing an antiulcer composition derived from evening primrose.

The anti-ulcer composition of the present invention for solving the above-mentioned problems is characterized by containing a solvent extract of evening primrose.
The anti-ulcer composition of the present invention is characterized by containing a solvent extract of evening primrose seeds.
Furthermore, the antiulcer composition of the present invention is characterized by containing a solvent extract of defatted evening primrose seeds.
Further, the anti-ulcer composition of the present invention is characterized in that the solvent extract is a hydrous ethanol extract having an ethanol concentration of 40 to 90% (wt / wt).

  According to the present invention, a component having an excellent anti-ulcer action can be taken as a safe extract from evening primrose. Thereby, diseases such as gastritis due to ammonia generated by urease produced by Helicobacter pylori, gastric ulcer, duodenal ulcer and the like can be effectively prevented or treated by protecting mucosa and activating protective factors.

  The anti-ulcer composition of the present invention is also applied to diseases other than ammonia such as gastritis, gastric ulcer and duodenal ulcer. For example, effectively prevent or treat diseases such as gastritis due to stress, gastric ulcer and duodenal ulcer, and gastritis due to stimulation with food and drugs, gastric ulcer and duodenal ulcer, etc. by the action of protecting mucosa and activating protective factors Can do.

Evening primrose is an annual or perennial grass of the genus Oenothera. In rare cases, the stems may become woody and form a shrub. The representative species are the following four species.
(1) Oenothera lacinia
(2) Oenothera stricta
(3) Oenothera biennis
(4) Oenothera erythrosepala
In the present invention, the kind of evening primrose is not limited, and any of them may be used.

Conventionally, as for evening primrose, evening primrose oil collected from its seed is widely known. Evening primrose oil is rich in γ-linolenic acid, and its efficacy is effective for obesity, diabetes, hypercholesterolemia, heavy alcohol drinkers, aging, and vitamin B ₆ deficiency. It is also known that evening primrose oil is effective for inhibiting the conversion of linoleic acid to γ-linolenic acid, which occurs in the case of viral infection, and treating patients with asthma and atopic eczema.
Physiological activity has been studied for the fat-soluble component of evening primrose seeds, but there are few reports on the physiological activity of substances other than the fat-soluble component.

In addition, the present condition is that the pressed rice cake produced in the process of producing evening primrose oil is partly used as feed and processed as industrial waste.
ADVANTAGE OF THE INVENTION According to this invention, while providing a new use about components other than the fat-soluble component of evening primrose seed, the composition for anti-ulcers can be extracted from the pressed cocoon after separation of evening primrose oil. It is extremely meaningful to extract a high-value-added anti-ulcer composition from the squeeze and to make effective use of resources.

  As a solvent for extracting the anti-ulcer composition of the present invention, water, methanol, ethanol, isopropyl alcohol, acetone, 1,3-butylene glycol, ethylene glycol, propylene glycol, glycerin, ethyl acetate or the like should be used. Can do. Two or more of these solvents may be mixed. Desirably, when water or ethanol is used as an extraction solvent, an active ingredient exhibiting an anti-ulcer action is efficiently extracted. In particular, hydrous ethanol is an extraction solvent that is less likely to reduce the activity of the active ingredient during extraction and is preferable from the standpoint of safety in the use of the extract in food. The kind of water for extraction is not particularly limited, and tap water, distilled water, mineral water, alkaline ionized water, deep water and the like can be used.

  When extracting the antiulcer composition of the present invention, for example, when using water-containing ethanol, the extraction temperature is 20 to 80 ° C., preferably about 40 to 50 ° C. This is because if the extraction temperature is too low, it becomes difficult to extract the active ingredient, and if the extraction temperature is too high, the activity of the active ingredient tends to decrease.

  The water-containing ethanol as the extraction solvent has an ethanol concentration of 40 to 90% (wt / wt), desirably an ethanol concentration of 60 to 80% (wt / wt). When the ethanol concentration is less than 40% (wt / wt), the extraction amount of the active ingredient becomes insufficient, and when it exceeds 90% (wt / wt), the oil content of evening primrose seeds easily dissolves in the solvent. Because it becomes. In addition, in order to improve the content rate of an active ingredient, it is good to perform ethanol extraction repeatedly, changing ethanol concentration in steps.

  It is desirable to use defatted evening primrose seeds for evening primrose seeds. This is because the active ingredient is concentrated in the defatted product by removing the oil in the seeds. As a degreasing method, for example, after compressing evening primrose seeds and separating the oil, the residual oil of the pressed product may be extracted and separated with a fat-soluble organic solvent.

  A preferred degreasing solvent is n-hexane. When n-hexane is used, the extracted oil can be used as an edible oil, and the extract of defatted evening primrose seeds can be easily used as a food material. In addition, when using evening primrose seed extract for uses other than foodstuffs, it is also possible to use not only n-hexane but another nonpolar solvent.

  As an extraction method for the anti-ulcer composition of the present invention, any method such as continuous extraction, immersion extraction, countercurrent extraction, and supercritical extraction can be employed, and an arbitrary apparatus is used at room temperature or under reflux heating. be able to.

As a specific extraction method, an extraction raw material (primate of evening primrose seed) is put into a treatment tank filled with an extraction solvent, and the active ingredient is eluted while stirring. For example, when water-containing ethanol is used as the extraction solvent, the extraction solvent is used in an amount of about 5 to 100 times (weight ratio) of the extraction raw material, and extraction is performed for about 30 minutes to 2 hours. The active ingredient is eluted in the solvent, and then filtered to remove the extraction residue to obtain an extract. Thereafter, the extract is subjected to treatments such as dilution, concentration, drying, and purification according to a conventional method to obtain an anti-ulcer composition.
Examples of the purification method include activated carbon treatment, resin adsorption treatment, ion exchange resin, liquid-liquid countercurrent distribution, and the like, but they are not used in large quantities when added to foods. It may be used unpurified.

  According to the inventors' investigation, the evening primrose seed extract contains a relatively large amount of polyphenols such as ellagic acid, pentagalloyl glucose, gallic acid, catechin, procyanidin, and proanthocyanidins. The anti-ulcer action of evening primrose seed extract is presumed to be largely due to the physiological activity of these polyphenols. Moreover, it is thought that anti-ulcer action is heightened by the synergistic effect of these polyphenols.

The anti-ulcer composition of the present invention can be used as a material for various foods and drinks.
Examples of food and drink include confectionery (gum, candy, caramel, chocolate, cookies, snacks, jelly, gummi, tablet confectionery, etc.), noodles (soba, udon, ramen, etc.), and dairy products (milk, ice cream, yogurt). ), Seasonings (miso, soy sauce, etc.), soups, beverages (juice, coffee, tea, tea, carbonated beverages, sports drinks, etc.), health foods (tablets, capsules, etc.), nutrition Supplementary foods (such as energy drinks) are listed. The evening primrose extract, preferably a defatted evening primrose seed extract, may be appropriately blended with these foods and drinks.

  These foods and drinks can be blended with various components depending on the type, for example, glucose, fructose, sucrose, maltose, sorbitol, stevioside, corn syrup, lactose, citric acid, tartaric acid, malic acid, succinic acid. Acid, lactic acid, L-ascorbic acid, dl-α-tocopherol, sodium erythorbate, glycerin, propylene glycol, glycerin fatty acid ester, polyglycerin fatty acid ester, sucrose fatty acid ester, sorbitan fatty acid ester, propylene glycol fatty acid ester, gum arabic, Food materials such as carrageenan, casein, gelatin, pectin, agar, vitamin Bs, nicotinic acid amide, calcium pantothenate, amino acids, calcium salts, pigments, fragrances and preservatives can be used. In addition, agaropectin, carrageenan, alginic acid, etc. of seaweed-derived agar derived from seaweed, mucopolysaccharide hyaluronic acid, compounds with acidic groups added to neutral polysaccharide, and Lamiaceae plants such as rosemary and sage that have been reported to have anti-ulcer activity Can contain carnosic acid and carnosol.

  Specifically, an evening primrose extract, preferably a defatted evening primrose seed extract spray-dried or freeze-dried together with powdered cellulose, is easily made into a powder, granule, tablet, or solution (food, instant food, etc.) Can be contained. Also, evening primrose extract, preferably defatted evening primrose seed extract, can be dissolved in, for example, fats and oils, ethanol, glycerin or a mixture thereof, and added to beverages or solid foods. If necessary, it can be mixed with a binder such as gum arabic or dextrin to form a powder or granules and added to a beverage or a solid food.

  When the anti-ulcer composition of the present invention is applied to foods and drinks, since the purpose is to prevent disease and maintain health, the total content of active ingredients in the food and drinks is 1 to 20 wt% or less. Is preferred.

  The anti-ulcer composition of the present invention may be used as a raw material for drugs (including pharmaceuticals and quasi drugs). It can be produced by appropriately blending an active ingredient evening primrose extract, preferably a defatted evening primrose seed extract, with the raw material for the pharmaceutical preparation. Examples of the raw material for preparation that can be blended in the anti-ulcer composition of the present invention include excipients (glucose, lactose, sucrose, sodium chloride, starch, calcium carbonate, kaolin, crystalline cellulose, cacao butter, hydrogenated vegetable oil, kaolin, Talc, etc.), binder (distilled water, physiological saline, ethanol water, simple syrup, glucose solution, starch solution, gelatin solution, carboxymethylcellulose, potassium phosphate, polyvinylpyrrolidone, etc.), disintegrant (sodium alginate, agar, carbonate) Sodium hydride, calcium carbonate, sodium lauryl sulfate, stearic acid monoglyceride, starch, lactose, gum arabic powder, gelatin, ethanol, etc.), disintegration inhibitors (sucrose, stearin, cocoa butter, hydrogenated oil, etc.), absorption enhancers (No. Quaternary ammonium base, sodium lauryl sulfate, etc. , Adsorbent (glycerin, starch, lactose, kaolin, bentonite, silicic acid, etc.), lubricants (purified talc, stearates, polyethylene glycol, and the like) and the like.

  In addition, when the anti-ulcer composition of the present invention is used for eradication treatment of Helicobacter pylori, it may be used in combination with other pharmaceuticals that exhibit antibacterial action and the like. For example, evening primrose extract, preferably defatted evening primrose seed extract, antibiotics (amoxicillin, clarithromycin, etc.), antiprotozoal agents (tinidazole, metronidazole, etc.), antitumor agents (bismuth preparation, sofalcone, pronotol, etc.), proton Pump inhibitors (omeprazole, lansoprazole, etc.) and the like may be appropriately blended.

  In general, the antiulcer composition according to the present invention can be administered orally in the form of tablets, pills, soft / hard capsules, fine granules, powders, granules, liquids and the like.

The dosage may vary depending on the administration method, medical condition, age of the patient, etc., but for adults, it can be generally administered as 0.5 to 5000 mg as an active ingredient per day, and usually about 0.5 to 3000 mg for children.
The blending ratio of the anti-ulcer composition can be appropriately changed depending on the dosage form, but is usually about 0.3 to 15.0 wt% when administered orally. In addition, since the dose varies depending on various conditions, a dose smaller than the above dose may be sufficient, or it may be necessary to administer beyond the range.

  Examples of the present invention will be described below. In addition, the Example shown below demonstrates in order to confirm the anti-ulcer action of the evening primrose extract by this invention, and the scope of the present invention is not limited to these products and production methods.

[Production of anti-ulcer composition]
Squeeze obtained in the process of producing evening primrose oil was used as a raw material for the anti-ulcer composition. First, 1 kg of evening primrose seeds was crushed and refluxed with N-hexane to obtain a defatted product by removing the oil remaining in the pressed rice cake. Next, the defatted product was refluxed with hydrous ethanol having an ethanol concentration of 60 wt%, and the ethanol extract was dried to obtain 60 g of evening primrose extract (Example 1: Anti-ulcer composition). In addition, the polyphenol density | concentration of evening primrose extract (Example 1) was about 60 wt%.

[Anti-ulcer test]
Example 1 The anti-ulcer test was carried out by orally administering 2% aqueous ammonia (0.5 ml (10 mg as ammonia)) per 100 g of rats to Wistar male rats (weighing 280 to 300 g) fasted for 24 hours. Ether lethal. The stomach was removed, 8 ml of 2% formalin was placed in the stomach and fixed for 10 minutes, and then the area of the incision injury (mm ² ) was measured along the large fistula using the Scion Image, and this was taken as the ulcer coefficient. The specimen was made into a suspension with 5% gum arabic powder, and 0.5 ml per 100 g rat was orally administered 30 minutes before administration of 2% ammonia water. The results are shown in FIG.

  As shown in FIG. 1, the average ulcer coefficient in the mice administered with 2% ammonia was 41.0, whereas the average ulcer coefficient in the mice administered with 500 mg / kg of the present invention was 1.6. Clearly, the product of the present invention was found to be effective as an anti-ulcer agent for ammonia ulcer by oral administration. As a result, it was revealed that the product of the present invention acts directly from the gastrointestinal mucosa and exhibits an effective effect as an anti-ulcer agent.

[Composition example]
The compounding example of the composition for antiulcers by this invention is shown. In the following formulation examples, an ethanol extract of defatted evening primrose seeds may be used as the “evening primrose extract”.
Formulation Example 1: Chewing gum
53.0wt% sugar
Gum base 20.0
Glucose 10.0
Minamata 16.0
Fragrance 0.5
Evening primrose extract (anti-ulcer composition) 0.5
100.0wt%

Formulation Example 2: Gummy
Reduced water tank 40.0wt%
Granulated sugar 20.0
Glucose 20.0
Gelatin 4.7
Water 9.68
Ume Juice 4.0
Ume Flavor 0.6
Dye 0.02
Evening Primrose Extract (Anti-ulcer composition) 1.0
100.0wt%

Formulation Example 3: Candy
50.0 wt% sugar
Minamata 33.0
Water 14.4
Organic acid 2.0
Fragrance 0.2
Evening primrose extract (anti-ulcer composition) 0.4
100.0wt%

Formulation Example 4: Yogurt (hard / soft)
Milk 41.5wt%
Nonfat dry milk 5.8
Sugar 8.0
Agar 0.15
Gelatin 0.1
Lactic acid bacteria 0.005
Evening primrose extract (anti-ulcer composition) 0.4
Perfume
Water residue
100.0wt%

Formulation Example 5: Soft capsule
Brown rice germ oil 87.0wt%
Emulsifier 12.0
Evening Primrose Extract (Anti-ulcer composition) 1.0
100.0wt%

Formulation Example 6: Soft drink
Fructose glucose liquid sugar 30.0wt%
Emulsifier 0.5
Evening Primrose Extract (Anti-ulcer composition) 0.05
Perfume
Purified water residue
100.0wt%

Formulation Example 7: Tablet
Lactose 54.0wt%
Crystalline cellulose 30.0
Starch degradation product 10.0
Glycerin fatty acid ester 5.0
Evening Primrose Extract (Anti-ulcer composition) 1.0
100.0wt%

Formulation Example 8: Tablet
76.4 wt% sugar
Glucose 19.0
Sucrose fatty acid ester 0.2
Evening primrose extract (anti-ulcer composition) 0.5
Purified water 3.9
100.0wt%

As described above, according to the present invention, the following excellent effects can be obtained.
(A) By ingesting a safe extract derived from evening primrose, diseases such as gastritis, gastric ulcer, and duodenal ulcer can be effectively prevented or treated by the action of protecting mucosa and activating protective factors.
(B) Since it is a safe extract derived from evening primrose, it can be safely used as a material for foods and drinks and medicines.
(C) Since an anti-ulcer composition with high added value can be obtained using defatted evening primrose seeds as a raw material, it is useful for effective utilization of resources.

FIG. 7 shows the results of an anti-ulcer test, and is a diagram showing the relationship between the dose of evening primrose extract (anti-ulcer composition) and the ulcer area (ulcer coefficient).

Claims (12)

A composition for anti-ulcer, comprising a solvent extract of evening primrose. The composition for anti-ulcer of Claim 1 whose said solvent extract is a solvent extract of evening primrose seed. The anti-ulcer composition according to claim 1, wherein the solvent extract is a solvent extract of defatted evening primrose seeds. The antiulcer composition according to claim 1, 2 or 3, wherein the solvent extract is a hydrous ethanol extract. The anti-ulcer composition according to claim 1, 2, or 3, wherein the solvent extract is a hydrous ethanol extract having an ethanol concentration of 40 to 90% (wt / wt). The composition for anti-ammonia ulcers containing the solvent extract of Claims 1-5. A food or drink comprising the anti-ulcer composition according to any one of claims 1 to 5. The chemical | medical agent containing the composition for antiulcers as described in any one of Claims 1-5. A composition for anti-ulcer, comprising polyphenols derived from evening primrose as an active ingredient. The antiulcer composition according to claim 9, wherein the polyphenol contains one or more selected from ellagic acid, pentagalloyl glucose, gallic acid, catechin, procyanidin, and proanthocyanidin. Food / beverage products containing the composition for anti-ulcers as described in any one of Claims 9 and 10. The chemical | medical agent containing the composition for anti-ulcers as described in any one of Claim 9 and 10.

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