WO2005089785A1 - アセロラ葉抽出物を含む血糖値上昇抑制剤およびage生成阻害剤ならびにそれらを含む食品 - Google Patents
アセロラ葉抽出物を含む血糖値上昇抑制剤およびage生成阻害剤ならびにそれらを含む食品 Download PDFInfo
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- WO2005089785A1 WO2005089785A1 PCT/JP2005/004564 JP2005004564W WO2005089785A1 WO 2005089785 A1 WO2005089785 A1 WO 2005089785A1 JP 2005004564 W JP2005004564 W JP 2005004564W WO 2005089785 A1 WO2005089785 A1 WO 2005089785A1
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- WIPO (PCT)
- Prior art keywords
- inhibitor
- leaf extract
- acerola
- blood sugar
- sugar level
- Prior art date
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- HCWCAKKEBCNQJP-UHFFFAOYSA-N magnesium orthosilicate Chemical compound [Mg+2].[Mg+2].[O-][Si]([O-])([O-])[O-] HCWCAKKEBCNQJP-UHFFFAOYSA-N 0.000 description 1
- 239000000391 magnesium silicate Substances 0.000 description 1
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- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
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- XNGIFLGASWRNHJ-UHFFFAOYSA-L phthalate(2-) Chemical compound [O-]C(=O)C1=CC=CC=C1C([O-])=O XNGIFLGASWRNHJ-UHFFFAOYSA-L 0.000 description 1
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7004—Monosaccharides having only carbon, hydrogen and oxygen atoms
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/105—Plant extracts, their artificial duplicates or their derivatives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
- A61K31/05—Phenols
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
- A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline
- A61K31/353—3,4-Dihydrobenzopyrans, e.g. chroman, catechin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/73—Rosaceae (Rose family), e.g. strawberry, chokeberry, blackberry, pear or firethorn
- A61K36/736—Prunus, e.g. plum, cherry, peach, apricot or almond
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
Definitions
- the present invention relates to a blood glucose elevation inhibitor and an AGE production inhibitor.
- Diabetes is a group of metabolic diseases in which a hyperglycemic state continues for a long time due to insufficient action of a hormone called insulin. If the hyperglycemic state continues, various complications such as neuropathy, cataract, renal disorder, retinopathy, arthrosclerosis, atherosclerosis, and diabetic gangrene may occur. Complications are primarily vascular disorders caused by non-enzymatic glycation, where proteins in the patient's blood bind sugar, and cell destruction caused by the accumulation of sorbitol, which occurs when sugar is metabolized. And neuropathy caused by Glycated proteins formed by binding proteins to sugars form compounds called advanced glycation end products (AGEs) when the reaction proceeds further. AGE is thought to contribute to the development of diabetic vascular disorders by binding to a specific receptor (RAGE) on vascular endothelial cells.
- RAGE specific receptor
- a blood sugar rise inhibitor for administration to a diabetic patient whose blood sugar level rises to an abnormal value after a meal, and digestion and absorption of carbohydrates to suppress the blood sugar level so as not to increase.
- Inhibiting a-Darcosidase inhibitors have been developed.
- Voglibose decarbose is known as a typical a-dalcosidase inhibitor.
- AGE generation As an harmful agent, for example, aminoguanidine, which is a carbonyl reagent, is known, and has attracted attention as an antidiabetic drug—an antidiabetic complication drug, and has been subjected to various clinical experiments.
- ⁇ -Darcosidase inhibitors derived from natural ingredients include perilla extract (Patent Document 1), yerba mate leaf extract (Patent Document 2), Rafu Asaba extract (Patent Document 3), and loquat leaf extract (Patent Document 4) )
- perilla extract Patent Document 1
- yerba mate leaf extract Patent Document 2
- Rafu Asaba extract Patent Document 3
- loquat leaf extract Patent Document 4
- an AGE production inhibitor derived from a natural component for example, an antidiabetic active substance and an antidiabetic complication active substance using an extract of rice rape, such as wild rice, and a method for producing the same (Patent Document 5) The power is still small.
- acerola is a tropical fruit of the citrus genus Hiragitrano, which is native to Caribbean islands. Acerola fruits are currently used as beverages and health foods around the world. However, there has been no study on useful substances contained in acerola leaves. Acerola leaves are an unused resource, and it is desired to find industrial value.
- Patent Document 1 JP-A-2000-102383
- Patent Document 2 Japanese Patent Application Laid-Open No. 2003-146900
- Patent Document 3 Japanese Patent Application Laid-Open No. 2002-053486
- Patent Document 4 JP 2003-128571 A
- Patent Document 5 Patent No. 3334016
- An object of the present invention is to provide a natural product-derived inhibitor of blood sugar level increase and an AGE production inhibitor, and a food containing the same.
- the present invention includes the following inventions.
- An AGE production inhibitor comprising an acerola leaf extract and Z or a processed product thereof as an active ingredient.
- a blood sugar rise inhibitor and an AGE production inhibitor containing a natural product as an active ingredient, and a food containing them.
- FIG. 1 is a graph showing the results of measuring the maltase inhibitory activity of an extracted and purified acerola leaf prepared in Example 1 and comparing it with the extracted and purified acerola fruit.
- FIG. 2 is a graph showing the results of measuring the AGE production inhibitory activity of the extracted and purified acerola leaf extract prepared in Example 1.
- the present invention relates to a blood sugar rise inhibitor and an AGE production inhibitor comprising an acerola leaf extract and Z or a processed product thereof as active ingredients.
- the production location and varieties of acerola from which the acerola leaves used in the present invention are collected are not particularly limited. For example, Okibashi and Brazil. Since the blood sugar rise inhibitor and the AGE production inhibitor of the present invention contain natural products of acerola leaf extract and Z or a processed product thereof as active ingredients, they are less likely to have side effects.
- the present invention is also preferable in that it contributes to the effective use of acerola leaves, which are unused resources.
- the acerola leaves used for the extraction may be any of fresh acerola leaves, semi-dried leaves, and dried leaves.
- the acerola leaves used for extraction may be in the form of leaves themselves or may be appropriately ground or shredded.
- the acerola leaf extract is not particularly limited as long as it is extracted by a usual method.
- the acerola leaf extract may be concentrated if necessary.
- a processed product of acerola leaf extract can also be used.
- the “treated product of acerola leaf extract” includes, but is not limited to, a product obtained by purifying acerola leaf extract using various types of chromatography.
- the solvent used for the extraction is preferably water or a hydrophilic organic solvent.
- hydrophilic organic solvents include alcohols such as methyl alcohol, ethyl alcohol, glycerin, propylene glycol, and 1,3-butylene glycol, acetone, tetrahydrofuran, acetonitrile, 1,4-dioxane, pyridine, dimethyl sulfoxide, N, Known organic solvents such as N-dimethylformamide and acetic acid can be used.
- the above-mentioned hydrophilic organic solvent may be used as a mixture with water.
- the extraction conditions are not particularly limited, but a preferable temperature range is 0 to 120 ° C, particularly 20 to 50 ° C.
- the extraction time is preferably about 1 hour to 24 hours, particularly about 12 hours, and the amount of the solvent used for the extraction is preferably 120 times by mass relative to the raw material.
- an extract is obtained by removing the residue by filtration or centrifugation.
- the extract may be concentrated if necessary.
- the extract thus obtained may contain a sugar, an organic acid, and the like, it is also preferable to carry out a purification step for the purpose of removing them.
- Purification treatment means include normal phase or reverse phase chromatography, ion exchange chromatography, gel filtration, and the like. These purification treatment means may be appropriately combined.
- the acerola leaf extract and Z or a processed product thereof used in the present invention are shown in Examples. As shown, it has a blood sugar level increase inhibitory action and an AGE production inhibitory action. The effect may be due to the inclusion of polyphenols in the acerola leaf extract and / or its processed product.
- the composition of the polyphenols contained is unknown.It is considered to be a composition that is advantageous for exerting the effect of inhibiting blood glucose elevation and inhibiting AGE production
- the content of the acerola leaf extract and / or Z or the processed product thereof in the blood sugar level increase inhibitor or the AGE production inhibitor according to the present invention is not particularly limited as long as the desired action is achieved. Wow.
- the blood sugar level increase inhibitor or the AGE production inhibitor according to the present invention may contain an arbitrary component in addition to the acerola leaf extract and Z or a processed product thereof.
- the blood sugar increase inhibitor and the AGE production inhibitor of the present invention comprise an acerola leaf extract and
- Z or a processed product thereof may be formulated in combination with a known pharmaceutical carrier.
- the dosage form is not particularly limited and can be appropriately selected as necessary.In general, tablets, capsules, granules, fine granules, powders, liquids, syrups, suspensions, emulsions, elixirs, etc. It can be administered as an oral preparation or a parenteral preparation such as an injection, a drip, a suppository, an inhalant, a transdermal absorbent, a transmucosal absorbent, a patch, an ointment and the like.
- Oral preparations are produced in the usual manner using excipients such as starch, lactose, sucrose, mannitol, carboxymethylcellulose, corn starch, inorganic salts and the like.
- a binder In this type of preparation, a binder, a disintegrant, a surfactant, a lubricant, a fluidity promoter, a flavoring agent, a coloring agent, a flavor, and the like are appropriately used in addition to the above-mentioned excipients. Can be.
- binder examples include crystalline cellulose, crystalline cellulose 'carmellose sodium, methylcellulose, hydroxypropylcellulose, low-substituted hydroxypropylcellulose, hydroxypropinolemethinoresenorelose, and hydroxypropinolemethinoresenorelose.
- disintegrating agent examples include crystalline cellulose, methylcellulose, low-substituted hydroxypropinoresenololose, canolemelose, canolemelose kanoresum, canolemelose sodium, croscarmellose sodium, wheat starch, rice starch , Corn starch, potato starch, partially alpha starch, hydroxypropyl starch, sodium carboxymethyl starch and tragacanth.
- surfactant examples include soybean lecithin, sucrose fatty acid ester, polyoxyl stearate, polyoxyethylene hydrogenated castor oil, polyoxyethylene polyoxypropylene glycol, sorbitan sesquioleate, sorbitan trioleate, and monoester.
- examples include sorbitan stearate, sorbitan monopalmitate, sorbitan monolaurate, polysorbate, glycerin monostearate, sodium lauryl sulfate, and lauromacrogol.
- lubricant examples include wheat starch, rice starch, corn starch, stearic acid, calcium stearate, magnesium stearate, hydrated silicon dioxide, light caustic anhydride, synthetic aluminum silicate, and dry hydroxy acid.
- examples include dani aluminum gel, talc, magnesium aluminate metasilicate, calcium hydrogen phosphate, anhydrous calcium hydrogen phosphate, sucrose fatty acid esters, waxes, hydrogenated vegetable oils, and polyethylene glycol.
- fluidity promoter examples include hydrous silicon dioxide, light caustic anhydride, dry aluminum hydroxide gel, synthetic aluminum silicate, and magnesium silicate.
- the blood sugar increase inhibitor and the AGE production inhibitor of the present invention When administered as a liquid, syrup, suspension, emulsion, or elixir, the blood sugar increase inhibitor and the AGE production inhibitor of the present invention contain a flavoring agent and a coloring agent. Is also good.
- the present invention also relates to a food containing the above-mentioned blood sugar level increase inhibitor or AGE production inhibitor.
- the food of the present invention may be in any form such as confectionery (for example, candy, troche, jam, chewing gum), beverage (for example, soft drink including tea, alcoholic beverage) which can be made only by ordinary “food”. It may be a food having.
- the food of the present invention is for specified health use Food (eg, diabetic 'diabetic complication preventive foods) can also be ingested.
- the content of the blood glucose level increase inhibitor or the AGE production inhibitor in the food is not particularly limited as long as the content exerts a desired effect.
- the present invention also relates to a food containing the acerola leaf extract and Z or a processed product thereof. There is no example of applying acerola leaves to food.
- the acerola leaves were homogenized, and 3 times the volume of distilled water was added, followed by extraction for 1 hour. This operation was performed twice, centrifuged, filtered, freeze-dried, and dissolved again in distilled water. This solution is applied to a C18 cartridge column (Waters Sep-Pak Vac 35cc C18 cartridge column), washed with distilled water, eluted with a 0.2% TFAZ methanol solution, and the eluted fraction is concentrated to dryness to extract and purify the product. Got.
- the polyphenol content of the extracted and purified product was measured by the Folin-Denis method. That is, 0.1 ml of a solution obtained by dissolving the purified product in distilled water to a concentration of 0.5 mgZml, 2.9 ml of distilled water, and 0.5 ml of Folin-Ciocatalteu reagent (MERCK) are mixed. did . After standing for 3 minutes, a 20% sodium carbonate solution was added, and after standing for another 60 minutes, the absorbance at 650 nm was measured. The calibration curve was created using catechin as a standard substance.
- the polyphenol content of the extracted and purified product obtained here was 25%.
- the inhibitory action on maltase was measured by the following method.
- a 9-fold amount of 56 mM maleic acid buffer (pH 6.0) was added to the rat intestinal acetone powder for sale, and the mixture was homogenized with a glass homogenizer, followed by centrifugation, and the supernatant was collected.
- the maltase reaction was used by diluting the crude enzyme solution 20-fold.
- 0.6 ml of a 2 mg Zml concentration of a sample solution was added to 0.6 ml of a 2% maltose solution, and the mixture was incubated at 37 ° C. for 5 minutes. For 120 minutes. After heating in boiling water for 10 minutes to inactivate the enzyme, centrifugation is performed and glucose in the supernatant is removed. The amount was determined by HPLC.
- HPLC conditions are as follows.
- the same amount of distilled water was used in place of the sample solution as a control, and the amount of glucose was measured in the same manner.
- the result of the control was defined as a maltase inhibition rate of 0%.
- FIG. 1 shows the results measured by the above method.
- FIG. 1 also shows, as a comparative example, the results obtained by measuring the acerola fruit in the same manner as the leaves.
- FIG. 1 shows that the extracted and purified acerola leaf extract has a maltase inhibitory activity.
- FIG. 2 shows the results measured by the above method.
- FIG. 2 shows that the extracted and purified acerola leaf extract has the same level of AGE generation inhibitory activity as aminoguanidine.
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
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- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Mycology (AREA)
- Botany (AREA)
- Diabetes (AREA)
- Nutrition Science (AREA)
- Microbiology (AREA)
- Molecular Biology (AREA)
- Polymers & Plastics (AREA)
- Food Science & Technology (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Alternative & Traditional Medicine (AREA)
- Biotechnology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Medical Informatics (AREA)
- General Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Obesity (AREA)
- Hematology (AREA)
- Endocrinology (AREA)
- Emergency Medicine (AREA)
- Medicines Containing Plant Substances (AREA)
- Coloring Foods And Improving Nutritive Qualities (AREA)
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Abstract
Description
Claims
Priority Applications (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US10/593,465 US20070207229A1 (en) | 2004-03-19 | 2005-03-15 | Inhibitor of blood glucose level elevation and inhibitor of age generation comprising acerola leaf extract and food product comprising either thereof |
EP05720819A EP1738658A1 (en) | 2004-03-19 | 2005-03-15 | Acerola leaf extract-containing blood sugar level increase inhibitor and age formation inhibitor, and food containing them |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2004-080520 | 2004-03-19 | ||
JP2004080520A JP4414794B2 (ja) | 2004-03-19 | 2004-03-19 | アセロラ葉抽出物を含む血糖値上昇抑制剤およびage生成阻害剤ならびにそれらを含む食品 |
Publications (1)
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WO2005089785A1 true WO2005089785A1 (ja) | 2005-09-29 |
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PCT/JP2005/004564 WO2005089785A1 (ja) | 2004-03-19 | 2005-03-15 | アセロラ葉抽出物を含む血糖値上昇抑制剤およびage生成阻害剤ならびにそれらを含む食品 |
Country Status (5)
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US (1) | US20070207229A1 (ja) |
EP (1) | EP1738658A1 (ja) |
JP (1) | JP4414794B2 (ja) |
CN (1) | CN1933846A (ja) |
WO (1) | WO2005089785A1 (ja) |
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JP4532257B2 (ja) | 2004-12-22 | 2010-08-25 | 株式会社ニチレイバイオサイエンス | アセロラ由来の新規ポリフェノール配糖体 |
DE102008041918A1 (de) * | 2008-09-09 | 2010-03-11 | Evonik Degussa Gmbh | Silanolkondensationskatalysatoren zur Vernetzung von gefüllten und ungefüllten Polymer-Compounds |
WO2010110640A1 (en) | 2009-03-24 | 2010-09-30 | Universiti Putra Malaysia | Anti-diabetic nutraceutical composition from palm leaf extract |
JP5804391B2 (ja) * | 2012-03-08 | 2015-11-04 | 株式会社アップウェル | 抗糖化剤 |
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- 2005-03-15 EP EP05720819A patent/EP1738658A1/en not_active Withdrawn
- 2005-03-15 WO PCT/JP2005/004564 patent/WO2005089785A1/ja not_active Application Discontinuation
- 2005-03-15 US US10/593,465 patent/US20070207229A1/en not_active Abandoned
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Also Published As
Publication number | Publication date |
---|---|
CN1933846A (zh) | 2007-03-21 |
US20070207229A1 (en) | 2007-09-06 |
JP2005263726A (ja) | 2005-09-29 |
JP4414794B2 (ja) | 2010-02-10 |
EP1738658A1 (en) | 2007-01-03 |
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