JP2007238454A - Angiogenesis inhibitor - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide an angiogenesis inhibitor expecting effect of preventing or treating a solid cancer, diabetic retinopathy, rheumatism, atherosclerosis, psoriasis, etc. <P>SOLUTION: The present invention uses one or more kinds of extracts selected from Pleurotus pulmonarius, Pholiota adiposa and Naematoloma sublateritium as the angiogenesis inhibitor. The present invention can provide a composition having angiogenesis inhibiting action by formulating one or more kinds of extracts selected from Pleurotus pulmonarius, Pholiota adiposa and Naematoloma sublateritium with various kinds of compositions such as foods, beverages, quasi-drugs and cosmetics. <P>COPYRIGHT: (C)2007,JPO&INPIT

Description

  The present invention relates to an angiogenesis inhibitor that exhibits an excellent effect. More specifically, the present invention relates to an angiogenesis inhibitor containing one or more extracts selected from Ushiratake, Numerisugitake, and Kuritatake.

  Angiogenesis is an in vivo phenomenon that occurs during organogenesis, wound healing and inflammation repair, but is known to be involved in many diseases such as solid cancer, diabetic retinopathy, rheumatism, atherosclerosis, and psoriasis. It has been. In particular, angiogenesis plays a major role in the development and growth of cancer. In order to treat or prevent such diseases that accompany abnormal angiogenesis, development of angiogenesis inhibitors has been actively conducted in recent years.

  For example, culture supernatants of human amniotic epithelial cells (see Patent Document 1), carboline derivatives (see Patent Document 2), polyalkoxyflavonoids (see Patent Document 3) and the like have already been reported as angiogenesis inhibitors.

JP 2002-201138 A JP 2003-321363 A JP 2004-83417 A

  As described above, angiogenesis inhibitors are known to be effective for various diseases caused by abnormal angiogenesis, but their functions as angiogenesis inhibitors and side effects when taken daily are still unknown. There are many points, and there are not enough things yet. The present invention has been made in view of such circumstances, and an object of the present invention is to find an active ingredient having an excellent anti-angiogenic action and provide it as an anti-angiogenic agent.

  The present inventors have examined various naturally-derived substances in order to find out components that can be applied as angiogenesis inhibitors. As a result, it has been found that one or more extracts selected from Ushiratake, Numerisugitake, and Kuritake exhibit an excellent anti-angiogenic action, and further investigations have been made to complete the present invention. That is, this invention provides the angiogenesis inhibitor which uses as an active ingredient the 1 type (s) or 2 or more types of extract chosen from the oyster mushroom, Numerisutake and Kuritatake. The above-mentioned angiogenesis inhibitor can be incorporated into foods and oral preparations, and can also be used in foods for the purpose of preventing or improving cancer due to its angiogenesis inhibitory action.

  ADVANTAGE OF THE INVENTION According to this invention, the angiogenesis inhibitor which has the outstanding effect can be provided. Moreover, this angiogenesis inhibitor can be mix | blended with a foodstuff or an internal use, and can also be utilized for the foodstuff etc. which aimed at prevention and improvement of cancer by the angiogenesis inhibitory effect.

Ushiratake, Numerisugitake, and Kuritatake can be used as the raw material of the present invention. Pleurotus pulmonarius is a fungus belonging to the genus Oleander genus, and occurs in dead or fallen trees of broadleaf trees. Numerisutaketake ( Pholiota adiposa ) is a fungus belonging to the genus Sugitake, Moegitakeceae , and occurs on fallen trees and stumps of willow and beech. Hypholoma lateritium (Naematoloma sublateritium) is a fungus of Strophariaceae hypholoma lateritium genus, occurs in hardwood and softwood dead tree.

  The extract of the present invention includes those obtained by pulverizing the above-mentioned Ushiratake mushroom, Numerisutake mushroom, and Kurita mushroom as they are, but it is desirable to use an extract extracted with a solvent or the like in consideration of usability. In the extraction, it may be used as it is, but considering the extraction efficiency, it is preferable to perform the extraction after performing processing such as shredding, drying, and pulverization. The extraction can be performed by a general method such as a method of immersing in an extraction solvent or an extraction method using a supercritical fluid or the like. The extraction temperature is preferably about 5 ° C. to the boiling point of the extraction solvent. The extraction time varies depending on the type of extraction solvent and the extraction temperature, but is preferably about 1 to 14 days.

  Extraction solvents include water, lower alcohols such as methanol, ethanol, propanol and isopropanol, polyhydric alcohols such as 1,3-butylene glycol, propylene glycol, dipropylene glycol and glycerin, ethers such as ethyl ether and propyl ether. , Solvents such as esters such as butyl acetate and ethyl acetate, and ketones such as acetone and ethyl methyl ketone can be used, and one or more of these can be selected and used. Further, physiological saline, phosphate buffer, phosphate buffered saline, or the like may be used. Furthermore, you may use 1 type, or 2 or more types of supercritical fluids and subcritical fluids, such as water, a carbon dioxide, ethylene, propylene, ethanol, methanol, ammonia.

  Extracts of the above-mentioned solvents of Ushiratake, Numerisutake, and Kuritake can be used as they are, but as long as the concentrated and dried solids are dissolved again in water or a polar solvent, or the physiological effects thereof are not impaired. You may use, after performing purification processes, such as decoloring, deodorizing, and desalting, or performing the fractionation process by column chromatography etc. The said extract, its processed material, and a fraction can also be lyophilized | freeze-dried after each process and fractionation, and can also be melt | dissolved and used for a solvent at the time of use.

  The extract of Ushiratake, Numerisutake, and Kurita has an excellent anti-angiogenic action and can be used as an anti-angiogenic agent. Examples of diseases that can be prevented or ameliorated by an angiogenesis inhibitor include solid cancer, diabetic retinopathy, rheumatism, atherosclerosis, and psoriasis. The angiogenesis inhibitor according to the present invention is an angiogenesis inhibitor. In addition to its action, it can also be expected to have the effect of preventing and improving such diseases.

  The above-mentioned angiogenesis inhibitor can be used alone, but can be used as an internal preparation or an external preparation by blending it into various compositions such as pharmaceuticals, foods, beverages, quasi drugs and cosmetics. I can do it. A composition containing an angiogenesis inhibitor can be administered orally or parenterally and should be used for the prevention and treatment of solid cancer, diabetic retinopathy, rheumatism, atherosclerosis, psoriasis, etc. Can do.

  The dosage form of the composition containing an angiogenesis inhibitor containing one or more extracts selected from Ushiratake, Numerisugitake, and Kuritatake as an active ingredient is arbitrary. General dosage forms such as oral preparations such as pills, granules, powders, liquids, syrups, gargles, throat cakes, parenterals such as patches, drops and the like. In the case of food, drinks, soft drinks, liquids such as dressings, gum drops, solid agents such as chocolate, and other general dosage forms such as yogurt, jelly, bread, side dish, seasoning, etc. It can be. In the case of an external preparation, it can be provided in various dosage forms such as aqueous lotions, emulsions such as emulsions and creams, aerosols filled with propellants, ointments, powders and granules.

  The composition containing an angiogenesis inhibitor containing one or more extracts selected from Ushiratake, Numerisugitake, and Kuritatake as active ingredients includes excipients used in pharmaceuticals, foods, beverages, cosmetics, Binders, extenders, disintegrants, surfactants, lubricants, dispersants, buffers, preservatives, preservatives, flavoring agents, fragrances, moisturizers, powders, pigments, emulsifiers, solubilizers, detergents UV absorbers, thickeners, drugs, resins, alcohols, and the like can be appropriately blended. Moreover, in the range which does not impair the effect of this invention, combined use with another angiogenesis inhibitor is also possible.

  In the following, the production examples of the extract of Ushiratake, Numerisutaketake, and Kuritake, the tests for evaluating each action, and the formulation examples as foods and oral preparations will be described in detail, but the technical scope of the present invention is not limited thereby. It is not limited.

[Production Example 1]
10 kg of 50% by weight ethanol aqueous solution was added to 1 kg of the dry pulverized product, and immersed for 7 days at room temperature. The extract was collected by filtration, and after removing the solvent, an ethanol extract was obtained.

[Production Example 2]
Nine liters of water was added to 1 kg of the dried pulverized product, and the mixture was extracted by refluxing at 90 ° C. for 6 hours. The extract was collected by filtration, and after removing the solvent, a hot water extract was obtained.

[Production Example 3]
Nine liters of methanol was added to 1 kg of the dry pulverized product, and immersed for 7 days at room temperature. The extract was collected by filtration, and after removing the solvent, a methanol extract was obtained.

[Production Example 4]
The sample was put into a supercritical extraction apparatus, and extracted using a supercritical fluid of carbon dioxide at 40 ° C. under a pressure of 15 MPa. The extract was collected to obtain a supercritical extract.

  Next, evaluation of the angiogenesis inhibitory effect using the extract of Ushiratake, Numerisutake, and Kurita is shown. Each extract shown in Table 1 was used as a sample.

  The evaluation was performed according to the following procedure. The angiogenesis kit (manufactured by Kurabo Industries Co., Ltd.) cultured in a 24-well plate was replaced with a sample culture solution adjusted to each concentration with an angiogenesis medium, and cultured for 11 days. The sample culture medium was exchanged on the 4th and 7th days. Next, after fixing the cells with 70% ethanol, blocking was performed with a buffer containing 1% BSA. Luminescence staining was performed using an anti-CD31 antibody by the enzyme antibody method. The length and area of the lumen formed by image processing were determined. In the evaluation, in addition to the sample culture solution, an angiogenesis medium and an angiogenesis medium supplemented with 10 ng / mL VEGF-A were used as a negative control and a positive control, respectively. The evaluation results of each sample are shown in Table 2 as relative values when the length and area of the lumen in the negative control (no sample added) are taken as 100.

  As is clear from Table 2, a significant angiogenesis-inhibiting action was observed in the medium supplemented with the extract of Usuhiratake, Numerisugitake, and Kuritatake. From this, it has been clarified that the extract of Ushiratake, Numerisutake, and Kurita has an excellent anti-angiogenic action.

  Then, the formulation example which mix | blended the extract of Usuhiratake, Numerisutake and Kuritatake concerning the present invention is shown.

[Prescription Example 1] Tablet (1) Ushiratake extract [Production Example 1] 100.0 (mg)
(2) Reduced maltose starch syrup 461.0
(3) Corn starch 15.0
(4) Glycerin fatty acid ester 12.0
(5) Fragrance 12.0
Production method: (1) to (3) were sifted and mixed uniformly, and then glycerin fatty acid ester and fragrance were added and mixed. Thereafter, tableting was performed by a conventional method to obtain a tablet having a total amount of 600 mg.

[Prescription Example 2] Granule (1) Numeri citrus extract [Production Example 2] 660.0 (mg)
(2) Vitamin B2 179.0
(3) Sucralose 11.0
(4) Powdered sugar 600.0
(5) Reduced maltose starch syrup 350.0
(6) Corn starch 400.0
Production method: (1) to (8) are uniformly mixed to obtain 2200 mg of granules by a conventional method.

[Prescription Example 3] Chewable tablet (1) Kurita extract [Production Example 2] 660.0 (mg)
(2) Reduced maltose starch syrup 1770.0
(3) Hydroxypropyl cellulose 30.0
(4) Lactose 500.0
(5) Sucralose 10.0
(6) Magnesium stearate 30.0
Production method: (1) to (8) are mixed uniformly to obtain 3000 mg of chewable agent by a conventional method.

[Formulation Example 4] Lotion (1) Ethanol 15.0 (wt%)
(2) Polyoxyethylene hydrogenated castor oil 0.3
(3) Fragrance 0.1
(4) Purified water 78.38
(5) Citric acid 0.02
(6) Sodium citrate 0.1
(7) Glycerin 1.0
(8) Hydroxyethyl cellulose 0.1
(9) Kurita extract [Production Example 2] 5.0
Production method: (2) and (3) are dissolved in (1). After dissolution, (4) to (8) are sequentially added, and then sufficiently stirred, (9) is added and mixed uniformly.

  An angiogenesis inhibitor comprising one or more extracts selected from Ushiratake, Numerisugitake, and Kuritatake of the present invention as an active ingredient has an excellent angiogenesis-inhibiting action, and is a solid cancer, diabetic retinopathy, rheumatism. The effect of prevention and treatment of atherosclerosis, psoriasis, etc. can be expected. Moreover, the foodstuff and external preparation which have an angiogenesis inhibitory effect can be provided by mix | blending the angiogenesis inhibitor of this invention with an internal use or external preparation.

Claims (2)

An angiogenesis inhibitor comprising one or more extracts selected from Usuhiratake, Numerisugitake, and Kuritatake as active ingredients. A composition comprising the angiogenesis inhibitor according to claim 1.