WO2009057724A1 - Composition de fraction adsorbée sur une résine synthétique dérivée de jute tossa à activité d'hypotenseur, agent hypotenseur ou aliment/boisson comprenant la composition de fraction adsorbée et procédé de production de la fraction adsorbée - Google Patents

Composition de fraction adsorbée sur une résine synthétique dérivée de jute tossa à activité d'hypotenseur, agent hypotenseur ou aliment/boisson comprenant la composition de fraction adsorbée et procédé de production de la fraction adsorbée Download PDF

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Publication number
WO2009057724A1
WO2009057724A1 PCT/JP2008/069817 JP2008069817W WO2009057724A1 WO 2009057724 A1 WO2009057724 A1 WO 2009057724A1 JP 2008069817 W JP2008069817 W JP 2008069817W WO 2009057724 A1 WO2009057724 A1 WO 2009057724A1
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Prior art keywords
synthetic resin
adsorbed fraction
extract
morohaya
composition
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PCT/JP2008/069817
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English (en)
Japanese (ja)
Inventor
Yuji Kubota
Hideki Kano
Takanobu Takihara
Atsuhiro Mitomi
Yuko Sagesaka
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Ito En, Ltd.
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Publication of WO2009057724A1 publication Critical patent/WO2009057724A1/fr

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    • 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)
    • 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
    • A23L2/00—Non-alcoholic beverages; Dry compositions or concentrates therefor; Their preparation
    • A23L2/52—Adding ingredients
    • 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
    • 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
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/12—Antihypertensives

Definitions

  • TECHNICAL FIELD The technical field of Morohea synthetic resin adsorbing fraction composition having vasorelaxant action, vasorelaxant or food and drink containing the adsorbing fraction composition, and adsorbing fraction composition
  • the present invention relates to a moroheia synthetic resin adsorbed fraction composition having a blood vessel relaxing action that is recovered by adsorbing a moroheiya extract solution with a synthetic resin adsorbent and elution-treating the adsorbed fraction with an elution solvent.
  • the present invention relates to a blood vessel relaxant comprising a hayer synthetic resin adsorbed fraction composition as an active ingredient, a food and drink comprising the moroheya synthetic resin adsorbed fraction composition, and a method for producing the morohea synthetic resin adsorbed fraction composition .
  • the vascular endothelium produces vascular regulatory factors such as nitric oxide (NO), and maintains and regulates vascular function by controlling vasodilation, muscle relaxation, blood fibrinolysis, and blood flow. It is known to do.
  • nitric oxide (NO) not only has a strong vasodilatory action, but also has a function of suppressing the progression of arteriosclerosis and the formation of thrombus. Therefore, the decrease in vascular endothelial function is not only a decrease in the function of the entire blood vessel, May cause arteriosclerosis and other cardiovascular diseases.
  • vascular endothelium adversely affects the vascular endothelium and reduces vascular endothelial function.
  • a vasorelaxant and a blood pressure lowering agent that do not depend on vascular endothelial function are desired.
  • General therapy is a method of treatment by weight loss, alcohol saving, exercise therapy such as aerobic exercise, and dietary therapy such as salt reduction, which is the basis for treatment of essential hypertension.
  • general therapy does not use drugs, there are advantages in terms of side effects or economic burden, but depending on the individual's willingness and the cooperative system of the surroundings, it is not always possible to achieve a certain effect on improving hypertension. There are problems such as.
  • pharmacotherapy is a therapy used for blood pressure that does not normalize with general therapy, such as when the effects of dietary therapy or exercise therapy are insufficient, or for hypertension with severe symptoms, and reliable hypotension can be expected.
  • Drugs used in pharmacotherapy range from calcium antagonists, angiotensin converting enzyme (ACE) inhibitors, angiotensin II receptor antagonists, diuretics, and sympathomimetic drugs. .
  • ACE angiotensin converting enzyme
  • angiotensin II receptor antagonists angiotensin II receptor antagonists
  • diuretics and sympathomimetic drugs.
  • sympathomimetic drugs since these drugs used as antihypertensive agents require long-term use, they generally have side effects such as digestive symptoms, orthostatic hypotension, and changes in metabolic function.
  • ACE inhibitors are widely known as side effects such as dry cough, dizziness, dizziness on standing, nausea, roar, and excessive sedation, which lowers QOL and causes compliance.
  • Drugs aimed at relaxing blood vessels may have side effects such as reflex tachycardia, palpitation, dry cough, hot flushes, hot flashes, and headaches. These medications need to be continued once they have been taken, and they cannot be stopped or changed in quantity at the patient's discretion, increasing the economic and mental burden. Therefore, there has been a demand for an effective therapy that has no fear of side effects, has a low economic and mental burden, can be sustained safely for a long period of time, and is effective. 2. Health foods, functional foods, health supplements, etc.
  • the sesame protein degradation product (containing sesame peptide) L eu- V a 1- T yr (L VY), which is obtained by defatting sesame and then extracting the protein and reacting with the degrading enzyme, is used as the relevant component.
  • Some have ACE inhibitory action and blood pressure lowering action.
  • dairy lactic acid bacteria beverages with ⁇ -aminobutyric acid (GABA) added are on the market.
  • G A ⁇ is a kind of amino acid, a typical inhibitory neurotransmitter, and has long been known to have a blood pressure lowering effect.
  • Tea drinks for foods for specified health use containing geniposide acid as the active ingredient are also commercially available.
  • Gelposide acid acts on the parasympathetic nerve and lowers blood pressure by smoothing blood flow.
  • Naoyuki Yamamoto et al. Reported that Yodalt produced by fermentation of lactic acid bacteria using milk as a raw material has a blood pressure lowering action under the title of “lactic acid bacteria and fermented milk products” (see Patent Document 1). .
  • milk protein, soy protein, or fish protein contains various ACE inhibitory peptides.
  • These natural product-derived ACE inhibitors are low toxic and safe.
  • the blood pressure-lowering peptides contained in these peptide groups derived from natural products are very small, In many cases, the amount of food consumed is large and the effect cannot be expected, and the ACE inhibitory activity is strong but the blood pressure lowering action is not so strong.
  • the causative substances of vasorelaxant action are clear, industrially stable production is possible, and vascular relaxants derived from natural products that are more effective and safer than conventional products. Health foods and health drinks containing them are required.
  • Morohaya (scientific name: Corchorus oitorius L.) is a kind of jute that originates in the Mediterranean region centered on Egypt, and is one of the food materials that has attracted particular attention in recent years due to its high nutritional value. Moroheiya, when minced or boiled, produces a unique slime like okra potato, which contains plant gum and viscous polysaccharides (mucopolysaccharides). Nutritionally, it is rich in vitamins and minerals, and has particularly high total rotin and calcium content. Carotene is about 12 times broccoli, vitamin B 1 is about 3 times tomato, vitamin B 2 is about 14 times pepper, calcium is about 2.4 times milk, dietary fiber is about 20 times lettuce It is said. For this reason, it has recently been cultivated in Japan, and its dry powder along with fresh leaves is gaining attention as a food material.
  • Morohaya Morohaya extract, Morohaya powder obtained by dry powdering it, so-called Morohaya extract, foods and compositions containing them, or production thereof
  • Patent Document 2 Takashi Yamamoto and others have reported a manufacturing method for extracting Morohaya extract by adding an organic acid for the purpose of lowering the viscosity of Morohaya extract for use in beverages.
  • Satoshi Inami and others have reported a composition containing an ethanol precipitate as an active ingredient in the water-soluble fraction of Morohaya leaves (see Patent Document 3).
  • this active ingredient is dietary fiber.
  • Masayuki Yoshikawa et al. Under the title of “Composition containing an aqueous extract of moroheiya”, obtained by heating and extracting moroheiya with purified water, concentrating the extract, and freeze-drying. It has been reported with respect to a composition comprising an aqueous extract of Morohaya having an essential component (see Patent Document 4). Furthermore, Masayuki Yoshikawa et al. Relates to a novel fatty acid or a salt thereof, a fatty acid extract, an isolation method thereof, and a pharmaceutical composition having an inhibitory action on nitric oxide (NO) production containing the fatty acid as an active ingredient. (Patent Document 5 3 ⁇ 4). 4. Blood pressure lowering effect of Morohaya
  • nicotianamine has been isolated as an ACE inhibitory active ingredient of Morohea extract (see Non-Patent Documents 3, 4, and 5).
  • Norio Yamaguchi et al. Have proposed a method for efficiently producing nicotianamine from an aqueous soybean extract (see Patent Document 6).
  • nicotianamine is not contained in Morohaya in a very small amount, and is actually not practical because it requires a large amount of raw materials and a complicated purification process to be used as a vasorelaxant or antihypertensive agent. A point has been pointed out.
  • Patent Document 1 Japanese Patent Laid-Open No. 7-1 2 3 9 7 7
  • Patent Document 2 Japanese Patent Laid-Open No. 10-1 9 1 9 2 2
  • Patent Document 3 Japanese Patent Laid-Open No. 7-6 9 9 1 0
  • Patent Document 4 JP 2000-26305 A
  • Patent Document 5 Japanese Patent Laid-Open No. 11-322667
  • Patent Document 6 Japanese Patent Laid-Open No. 2003-231 675
  • Non-Patent Document 1 J. Dairy Sci. 78: p.777-783
  • Non-Patent Document 2 J. Dairy Sci. 78: 1253 ⁇ 257
  • Non-Patent Document 4 Bulletin of Tokyo Kasei University, Vol. 38 (2), 59— 63, 1 998 “Studies on ACE inhibitors in foods”, Koichi Kimoto, Emiko Shimizu, Yuko Kuroda
  • the object of the present invention is to provide blood vessels derived from safe foods that are effective for hypertensive patients, particularly essential hypertensive patients said to account for 90% of them, and have no side effects and are suitable for long-term use. It is intended to provide a relaxing agent (vasodilator), a food or drink comprising the composition, particularly a food such as a health food or a health supplement, or a beverage comprising the same. Furthermore, it is providing the manufacturing method of those compositions. Means for solving the problem ⁇ In order to solve the above-mentioned problems, the present inventors have focused on Morohya, which has been attracting attention as a food material with high nutritional value in recent years, and conducted extensive studies on its blood vessel relaxing action, particularly blood pressure lowering action.
  • a morohea extract solution more preferably a morohea enzyme-treated solution obtained by treating morohaya with protease is adsorbed with a synthetic resin adsorbent, and the adsorbed fraction is eluted with an elution solvent and recovered.
  • the inventors have found that it is possible to produce a morohay synthetic resin-adsorbed fraction composition having a more excellent vasodilation or vasorelaxant action, that is, a blood pressure lowering action, and completed the present invention.
  • a drug having a vasorelaxing action is effective as a therapeutic or preventive agent for hypertension, heart failure, angina pectoris, valvular heart disease, ischemic heart disease or myocardial infarction, and particularly an antihypertensive agent.
  • the present invention is as follows.
  • a morohea synthetic resin adsorbed fraction composition having a blood vessel relaxing action which is obtained by adsorbing a moroheiya extract solution with a synthetic resin adsorbent and elution-treating the adsorbed fraction with an elution solvent.
  • moroheia synthetic resin adsorbed fraction composition as described in 1 above, wherein the morohae extract solution is a morohae enzyme-treated extract solution obtained by subjecting morohae to protease.
  • composition according to 1 to 4 above, wherein the synthetic resin adsorbent is a synthetic resin adsorbent based on an aromatic polymer.
  • Increment of amino acid amount of amino acid after acid hydrolysis, amount of amino acid before monoacid hydrolysis
  • the increment of amino acid is the concentration of mochahae synthetic resin adsorption fraction composition solution 2
  • G 1 y is more than 3 times the weight of Va 1;
  • At least one amino acid selected from Ser, A 1 a and L eu is at least 2 times the weight of Va 1, and at least one amino acid selected from Ser, A 1 a and L eu is I 1 more than 2 times the weight of e;
  • a rg is 1 weight times or more of V a 1 and A rg is 1 weight weight or more of I 1 e; 7.
  • Morohaya extract solution is adsorbed with a synthetic resin adsorbent, and the adsorbed fraction is eluted into the elution solvent.
  • moroheia extract solution is a moroheia enzyme-treated extract solution obtained by treating moroheiya with protease.
  • a vasorelaxant comprising the Morohaya synthetic resin adsorption fraction composition according to any one of 1 to 6 above.
  • a food or drink comprising the morroheia synthetic resin adsorbed fraction composition according to any one of 1 to 6 above.
  • the invention's effect is not limited
  • morohea synthetic resin adsorbed fraction composition of the present invention is derived from morohaya, which has been confirmed to be safe as food, it is extremely safe without side effects and can be taken on a daily basis.
  • the production method is very easy because the morohea extract solution is adsorbed with a synthetic resin adsorbent and the adsorbed fraction is recovered by elution with an elution solvent.
  • morroheia itself as a vegetable, its vasorelaxant action, especially blood pressure lowering action, is far superior to conventional morroheia extract that is not treated with a synthetic resin adsorbent. Are better.
  • a synthetic resin-adsorbed fraction composition having a more excellent blood vessel relaxation action, particularly a blood pressure lowering action, can be obtained. .
  • composition of adsorbing fractions of the morohea synthetic resin of the present invention is not only superior in vasorelaxant action and superior in sustainability, but also in the vascular endothelium as compared with the conventional moroheia extract that is simply extracted. Since the blood vessels are relaxed without acting on the blood vessels, the blood vessels can be relaxed and the blood pressure can be lowered without depending on the vascular endothelial function reduced by arteriosclerosis or other cardiovascular diseases.
  • Morohaya is a plant rich in vitamins, minerals, and dietary fiber, and has a high nutritional value, so when compared with a conventional plant that isolates and purifies a single component that has vasorelaxant and blood pressure lowering effects, When the synthetic resin-adsorbed fraction composition of the invention is ingested, a plurality of components can be ingested simultaneously, and further effects can be expected.
  • Moroheiya because it is made from the natural plant Moroheiya, it is inexpensive and highly safe, so it can be used in medicines, foods, especially foods for specified health use, health foods, vegetable juices, etc. Is preferred. Brief Description of Drawings Little. Fig. 1 shows changes in systolic blood pressure due to administration of Morohaya extract (A, B, B '. No adsorption treatment). (Test Example 1)
  • Fig. 2 shows changes in diastolic blood pressure due to administration of Morohaya extract (A, B, B '. No adsorption treatment).
  • Fig. 3 is a graph showing heart rate variability after administration of Morohaya extract (A, B, B '. No adsorption treatment). (Test Example 1)
  • Fig. 4 is a graph showing the mean blood pressure change by administration of Morohaya extract (A, B, B '. No adsorption treatment). (Test Example 1)
  • FIG. 5 is a diagram showing diurnal variation in systolic blood pressure in SHR rats.
  • FIG. 6 is a graph showing the effect of an enzyme-treated moroheiya extract (C. no adsorption treatment) prepared from moroheiya puree on blood pressure fluctuations. (Test Example 1)
  • FIG. 9 is a graph showing the effect of Moroheiya protease-untreated extract on the blood pressure fluctuation of synthetic resin-adsorbed fraction extract Ae2. (Test Example 2)
  • FIG. 8 is a graph showing a comparison of the effects of synthetic resin adsorbed fraction extracts (through fraction Bel and adsorbed fraction Be2) on blood pressure fluctuations. (Test Example 3)
  • FIG. 9 is a graph showing the effect of the moroheia enzyme-treated extract (B) before purification with an adsorbent on blood pressure fluctuations. (Test Example 3)
  • FIG. 10 is a graph showing an increase in adsorbed fraction extract due to protease treatment of Morohaya leaves. (Test Example 4)
  • FIG. 11 is a graph showing blood pressure lowering action by single administration of Morohaya synthetic resin adsorption fraction extract B e 2. (Test Example 5)
  • FIG. 12 is a graph showing the suppression effect on blood pressure increase by long-term administration of Morohaya synthetic resin adsorbed fraction extract B e 2. (Test Example 6)
  • Fig. 13 is a diagram showing the results of measuring the ACE inhibitory activity of Morohella synthetic resin adsorbed fraction extract B e 2 (Test Example 7).
  • Fig. 14 is a diagram showing the vasorelaxant action of Morohella synthetic resin adsorbed fraction extract B e 2. (Test Example 7)
  • FIG. 15 is a diagram showing the vasorelaxant action of the purified morohaya synthetic resin adsorbed fraction extract. (Test Example 7)
  • FIG. 16 is a graph showing changes in heart rate after administration of the purified Morroheia synthetic resin adsorbed fraction extract. (Test Example 8)
  • FIG. 17 is a diagram showing the vasorelaxing action of each fraction of purified Morroheia synthetic resin adsorbed fraction extract Be 2.
  • FIG. 18 is a diagram showing the results of a confirmation test on the amino acid composition of the protein in the moroheiya synthetic resin adsorbed fraction composition. (Test 9)
  • FIG. 19 is a diagram showing that Morohaya synthetic resin adsorbed fraction extract B e 2 has an action of relaxing blood vessels without depending on vascular endothelium.
  • the morohaya synthetic resin adsorbed fraction composition of the present invention can be obtained by adsorbing a morohea extract solution with a synthetic resin adsorbent and then eluting the adsorbed fraction with an elution solvent.
  • the morohea extract solution as a raw material can be obtained, for example, by adding water or warm water to the morohaya leaf and extracting it. Specifically, water or warm water is added to the moro-hay leaves from which the hard stalks have been removed, and then steam heating is applied to break the frame, and then the crushed mogu-haha leaves are dried with hot air. Therefore, it can be obtained by adding 10 to 40 times, preferably about 20 to 30 times the weight of distilled hydrothermal water to the dried morohea leaves.
  • moroheiya any part of the above-ground part excluding seeds may be used, but a leaf part from which a hard stem part has been removed is particularly preferred. After steam heating, crush and dry with hot air , 0 is preferably used as a material, but the method for preparing the dried leaf is not particularly limited, and a commercially available product can be used if necessary.
  • undried materials such as fresh leaves of moroheiya and puree.
  • it can be conveniently obtained by dissolving a commercially available morohea extract powder in water or warm water, or it may be extracted from morohea puree.
  • the morohaya extract solution is an aqueous solution containing the morohea extract component, and the morohaya extract solution from the morohaya leaf solution obtained by mixing the morohaya water solution, that is, water or warm water with the morohaya leaf solution.
  • it means a morohea extract solution or morohea puree aqueous solution in which morohea extract powder is dissolved in water.
  • Preferred is a moroheia enzyme-treated extract solution that has been subjected to protease treatment.
  • Protease treatment can be obtained by allowing a proteolytic enzyme, ie, protease, to act on a morohea extract, morohaya extract solution or morohya puree solution in which morohea extract powder is dissolved in water.
  • a proteolytic enzyme ie, protease
  • the morohea extract solution or morohea enzyme-treated exhalation solution thus obtained is adsorbed with a synthetic resin adsorbent, passed through the synthetic resin adsorbent, pushed with water, and then passed, for example, 60% ethanol. By recovering and recovering it as a liquid, it can be recovered as a resin-adsorbed fraction, thereby obtaining the desired morohea synthetic resin-adsorbed fraction composition.
  • a synthetic resin adsorbent By elution treatment with a solvent, an elution solvent suitable for the synthetic adsorbent used can be selected.
  • an aromatic synthetic resin adsorbent when used, a large amount of water or warm water may be used, and 50 to 70%, preferably 55 to 65% for increasing efficiency. Ethanol diluted with water to a concentration can be used. More specifically, after passing the morohea extract solution or the morohea enzyme-treated extract solution through the synthetic resin adsorbent packed column, the column discharge liquid is Brix 1% or less, preferably Brix 0.5, as measured by Brix. The adsorbed fraction may be recovered by thoroughly washing with pure water or the like so as to be less than% and then eluting with an elution buffer such as ethanol of an appropriate concentration.
  • an elution buffer such as ethanol of an appropriate concentration.
  • the adsorbate can be efficiently recovered by passing the liquid in an amount of 1 to 10 times the volume, more preferably 1 to 5 times, and even more preferably 1 to 2.5 times.
  • the adsorbate can be recovered by washing with pure water and then passing 3 times the resin volume.
  • the filtration operation may be performed by suction filtration using ⁇ ⁇ 2 filter paper after filtration through a sieve with an opening of 850 ⁇ .
  • a further purified adsorption fraction or composition it can be further purified using cation exchange column chromatography or gel filtration chromatography.
  • the solution recovered from the fraction can be concentrated under reduced pressure to an appropriate concentration, or it can be lyophilized and stored as a powder.
  • the production method of the fraction treatment composition of the present invention is as shown in the following table.
  • Moroheiya Production Picking Cut'Trimming ⁇ Washing—Steam Branching ⁇ Dehydration—Hot Air Drying—Crushing—Hydrolysis—Heating ⁇ Microbial Protease Enzyme Treatment (—Enzyme Deactivation) ⁇ Solid-Liquid Separation—Filtration—Synthetic Adsorbent Column Flow-water push- 60% ethanol flow (at the same time recovering the discharged liquid as an adsorbed fraction) ⁇ vacuum concentration ⁇ lyophilization The moroheiya synthetic resin adsorbed fraction obtained in this way is used after removing the alcohol. It can be used as a beverage or in other fruit juices, vegetable juices, or mixed juices.
  • the synthetic resin adsorbent used may be either a hydrophilic synthetic resin adsorbent or a hydrophobic synthetic resin adsorbent. In order to recover a composition having an effective vasorelaxant action, particularly a blood pressure lowering action.
  • a preferable adsorbent is a hydrophobic synthetic resin adsorbent.
  • Examples of the resin matrix of the hydrophobic synthetic resin adsorbent include a styrene polymer, a styrene-divinylbenzene copolymer, a styrene-acrylic acid amide copolymer, and a phenol resin.
  • a preferred synthetic resin adsorbent is a porous adsorbent suitable for adsorbing water-soluble low-molecular substances, specifically, a porous modified polystyrene synthetic adsorbent, that is, an aromatic resin such as styrene.
  • porous modified polystyrene-based synthetic adsorbent obtained by chemically modifying and bonding a polar group such as bromine to the base.
  • porous synthetic adsorbents with a large surface area are preferred! /.
  • the specific surface area of the synthetic resin adsorbent is 100 to 1200 mg, preferably about 250 to 900 m 2 Zg.
  • the preferable pore volume, particle size distribution, and most frequent radius of the synthetic resin adsorbent are 0.9 to L: 6 mL / g, respectively, 250 m or more is 90% or more, and 30 to 260 angstroms.
  • Sepabeads registered trademark; Mitsubishi Chemical Corporation
  • These synthetic resin adsorbents may be pre-treated prior to the adsorption treatment.
  • the adsorbent can be washed with a solvent such as methanol to remove impurities, and further washed with water to remove the solvent such as methanol.
  • the treatment with these adsorbents can be carried out by either the batch method or the column method, but the column method that can efficiently treat with a relatively small amount of adsorbent is preferred.
  • the treatment with the adsorbent may be performed at least once.
  • the ratio between the adsorbent and the extract can be selected according to the type of adsorbent used.
  • the morohea extract solution as an object of the synthetic resin adsorption treatment is not particularly limited as long as it is a solution containing a morohea extract component, particularly an aqueous solution.
  • a morohaya enzyme-treated extract solution that has been subjected to a proteolytic enzyme, that is, a protease treatment, further excellent vasodilation or vascularization It is possible to bring about a relaxing action, that is, a blood pressure lowering action.
  • a morohea enzyme-treated extract solution subjected to such protease treatment can be obtained as follows.
  • Morohaya enzyme-treated extract solution is Morohaya water solution, that is, Morohaya extract from Morohaya leaf solution in which Morohaya leaves are mixed with water or warm water, Morohaya extract aqueous solution or Morohaya puree solution in which Morohaya extract powder is dissolved in water. It can be obtained by reacting a protease with a protease. For example, in the case of Morohaya leaves, water or warm water is added to Morohaya leaves from which the hard stem portion has been removed, and then steam heating is performed to crush the leaves.
  • hot water of about 10 to 40 times, preferably about 20 to 30 times the weight of distilled water is added to the dried mouth-leaved leaves obtained by drying the crushed morohaya leaves with hot air. To do. Then, after heat sterilization at a temperature of 95 ° C or higher, cool to an appropriate temperature and dry the raw material with an appropriate amount of protease dissolved in a small amount of water while keeping the liquid temperature in the water bath. Appropriate amount is added to the weight of leaf or dry leaf. After adding the protease, stir every 10 minutes, 30 minutes to 2 hours, preferably 45 minutes to 90 minutes after the addition of the protease, and after 5 minutes to 90 minutes at 95 ° C to boiling S.
  • Protease is inactivated by holding for 0 minutes, filtered through a sieve with an opening of 8500 ⁇ , and suction filtered using No. 2 filter paper to obtain a moroheia enzyme-treated extract solution. It can.
  • a solution after filtration preferably a solution from which at least solid-liquid separation is performed to remove Morohaya leaves or the like is used.
  • Treatment conditions such as solution temperature, enzyme concentration, and pH for protease treatment may be adjusted so that the protease to be used works optimally.
  • the enzyme used for preparing the morohea enzyme-treated solution there are no particular limitations on the enzyme used for preparing the morohea enzyme-treated solution, as long as it is a protease enzyme, but preferred is an endopeptidase or a complex enzyme mainly composed of an endopeptidase. A plurality of enzymes can also be used in combination.
  • the proteolytic enzyme or protease used in the present invention is a peptide bond hydrolysis product.
  • An enzyme that catalyzes a reaction is preferably an endo-type enzyme or an end-type complex enzyme.
  • proteolytic enzymes produced by the genus Bacillus are more preferable.
  • proteolytic enzymes produced by Bacillus subtilis and Bacillus thermoproteolyticus are more preferable.
  • a combination of multiple enzymes can also be used.
  • P H when the protease treatment, treatment temperature, treatment time, treatment concentration is not particularly limited, may be appropriately selected depending on the enzyme used.
  • treatment concentration is 0. 1 to 1.0 wt 0/0 are preferred.
  • treatment concentration is the dry weight of Morohaya. 0.1 to 1.0% by weight is preferred.
  • the enzyme is deactivated by heating, and solid-liquid separation is performed by any method such as filtration, and the extract is recovered.
  • the method for deactivating the enzyme is appropriately selected depending on the enzyme used, but can be performed by heating, for example, it can be left at 95 ° C to boiling for 5 to 10 minutes.
  • “Moguchiha synthetic resin adsorbed fraction composition” refers to a synthetic resin adsorbent obtained by treating a moroheiya extract solution, preferably a morohaea proteolytic enzyme-treated extract solution with a synthetic resin adsorbent, and separating the adsorbed fraction by solution separation. It means a fraction composition, specifically, a moorhae extract, which is obtained from a moorhaha leaf solution obtained by mixing mochahaha leaves with water or warm water.
  • Spilled solution a mohair hay extract aqueous solution in which morohea extract powder is dissolved in water or a morohea extract solution such as morohea puree solution, or a morohea enzyme-treated extract solution obtained by subjecting these to protease treatment is adsorbed with a synthetic resin adsorbent
  • a synthetic resin adsorbed fraction composition obtained by elution treatment by passing through a synthetic resin adsorbent and pushing it with water, and then recovering by passing, for example, 60% ethanol.
  • These synthetic resin adsorbed fraction compositions may be in liquid or solid form, and the synthetic resin adsorbed fraction liquid itself, a concentrated concentrate obtained by concentrating it, and a powder obtained by freeze-drying them, or A tablet formed by solidifying powder may be used.
  • a morohea extract solution or a morohea enzyme-treated extract solution obtained by subjecting these to a protease is adsorbed with a synthetic resin adsorbent, and the adsorbed fraction is eluted with an elution solvent.
  • the synthetic resin adsorbed fraction composition and the dried and powdered composition may be referred to as a moroheiya fractionation treatment kiss or fractionation treatment kiss, or an adsorption treatment exhalation or adsorption fraction extract.
  • an elution solvent suitable for the synthetic resin adsorbent to be used can be selected.
  • an aromatic synthetic resin adsorbent is used, a large amount of water may be used, and in order to increase efficiency, water is added to a concentration of 50 to 70%, preferably 55 to 65%. Diluted ethanol can be used.
  • morohaya fractionation treatment solution and the concentrated solution obtained by concentrating it can be used as beverages after being subjected to phenol recall, or mixed with other soft drinks such as fruit juice and vegetable diuse.
  • the Morohaya synthetic resin adsorbed fraction composition composed of a lyophilized powder or solid tablet can be used as a health food, a functional food, a health supplement, etc., as well as a soft drink or food. It can be used as a compounding agent.
  • the morohaya synthetic resin adsorbed fraction composition of the present invention can be effectively used as a food, a food additive, or a packaged beverage in addition to a pharmaceutical.
  • Preferred forms of foods and drinks containing the moroheiya synthetic lunar adsorbed fraction composition of the present invention include: koji, jelly, tablet confectionery, beverages, soup, koji containing the synthetic resin adsorbed fraction composition Foods and beverages such as rice crackers, Japanese confectionery, frozen confectionery, baked confectionery, etc., particularly preferably a fruit juice beverage comprising the synthetic resin-adsorbed fraction composition, It is a packaged beverage such as vegetable juice, fruit vegetable juice, tea beverage, coffee beverage, sports drink.
  • the moroheiya synthetic resin adsorbed fraction composition obtained in the present invention has little taste and odor specific taste, it can be ingested by oral administration in liquid or solid form.
  • it can be mixed with excipients and administered in the form of powder, granules, tablets, capsules and the like.
  • the intake varies depending on the age and blood pressure level, but is usually 10 mg to 2000 mg at a time in powder conversion, preferably 50 mg to 1 000 mg at a time, more preferably 100 mg to 50 Omg at a time.
  • the effect can be obtained with 1 to 3 intakes per day, but the number can be increased as needed.
  • it is 50 mg to 2500 mg, more preferably 100 mg to 80 Omg per 500 mL.
  • the mocha hae synthetic resin adsorbed fraction composition obtained by the present invention is administered in the form of powder, granules, tablets, capsules or the like as such or mixed with excipients or the like as appropriate for the convenience of formulation. be able to.
  • it can be added to various foods such as rice cakes, jelly, tablet confectionery, beverages, soup, rice cakes, rice crackers, Japanese confectionery, frozen confectionery, baked confectionery, and ingested.
  • it is used by blending an appropriate amount with other foods and beverages, particularly preferably vegetable juice, fruit juice, vegetable fruit juice mix juice, tea beverage, coffee beverage, sports drink and the like. In this way, not only can the nutrients contained in vegetable juice etc. be taken on a daily basis, but also hypertensive consumers can take blood pressure elevation suppressors very naturally.
  • the examination of the blood pressure lowering effect of the mocha haeha synthetic resin adsorbed fraction composition of the present invention is to orally administer the moroheia extract of the present invention to spontaneously hypertensive rats, and measure the blood pressure before and after administration. Went by.
  • the mechanism of the vasodilatory / relaxation action, that is, the blood pressure lowering action, of the composition of adsorbing fractions of the moroheia synthetic resin of the present invention is the nicotine included in the moroheia leaves that have been reported so far. It was also confirmed that it was not due to the ACE inhibitory activity that anamin had, but due to vasorelaxation and vasodilation. That is, it was confirmed that the blood pressure lowering action of the morohaya enzyme-treated kiss of the present invention is not due to nicotianamine contained in the morohaya leaf. The present invention has been completed based on these new findings.
  • the action and effect of the moroheiya synthetic resin adsorbed fraction composition of the present invention were examined in detail, it decreased well particularly for high blood pressure, and slightly decreased blood pressure for slightly higher blood pressure. It was found that the effect was effective according to the degree of hypertension. In addition, it was confirmed that long-term administration can suppress an increase in blood pressure, that blood pressure does not increase suddenly even when administration is stopped, and that there is no sudden rebound due to forgetting to take it. It was. Thus, the synthetic resin-adsorbed fraction composition of the present invention has extremely high safety as well as effectiveness.
  • the mocha hae synthetic resin adsorbed fraction composition of the present invention is obtained by treating a moro hae extract solution, preferably an moro haeya proteolytic enzyme treated extract solution with a synthetic resin adsorbent, and easily separating the adsorbed fraction containing the active ingredient by solution separation. It can be obtained after separation and purification, and its vasorelaxant action, especially blood pressure lowering action, is stronger compared to the conventional Morohaya extract, which has not been treated with Morohaya leaves themselves or a synthetic moonlight adsorbent.
  • the vasorelaxant of the present invention is useful as a therapeutic or preventive agent for hypertension, heart failure, angina pectoris, valvular heart disease, ischemic heart disease or myocardial infarction, particularly as a blood pressure lowering agent.
  • Morohaya is a plant rich in vitamins, minerals, dietary fiber and high nutritional value. Therefore, when compared with a single component that has a blood pressure lowering effect, it is Since the hayer synthetic resin adsorbed fraction composition contains a plurality of components, further effects can be expected.
  • morohea fractionated extract of the present invention is not only effective but also highly safe, so that it can be used for beverages such as pharmaceuticals, foods, especially foods for specified health use, health foods, vegetable juices, It is particularly suitable for packaged beverages and the like. ⁇
  • moroheiya synthetic resin adsorbed fraction composition of the present invention As a result of further detailed analysis of the moroheiya synthetic resin adsorbed fraction composition of the present invention, it was divided into four fractions depending on the molecular weight (R> S 1> S 2> T), of which the molecular weight was A small fraction (S 2 and T) was found to have a strong blood pressure lowering effect. The fraction was found to contain adenine. The same purine bases, guanosine and adenosine, are contained in trace amounts and are not contained in the morohaya fractionation treatment kiss of the present invention.
  • Morohaya leaves from which hard stems had been removed were steam-heated and then ruptured and dried with hot air to obtain dried morohair leaves.
  • Distilled hydrothermal water around 60 ° C with a weight of 20 times is added to 50 g of the dried morohea leaves, heated to 95 ° C or higher, sterilized, and then cooled to 60 ° C. Stirring was carried out every 10 minutes while the liquid temperature was kept at 60 ° C in a water pass. After 1 hour, hold at 95 ° C for 5 minutes, filter with a sieve with an opening of 8500 ⁇ , and then suction filter with No. 2 filter paper to obtain a moroheiya extract solution It was. This extract solution was concentrated under reduced pressure and then freeze-dried to obtain 6.8 g of a brown powder. It is a so-called conventional Moroheiya extract. Hereinafter, this powder is referred to as “A”.
  • Synthetic adsorbent wet with pure water S P 2 0 7 (Mitsubishi Chemical Co., Ltd.) 80 c c was packed into a glass column, and + min. Pure water was passed through to form a S P 2 0 7 packing power ram.
  • Morohaya leaves from which hard stems had been removed were steam-heated, crushed and dried with hot air to obtain dried Morrohair leaves.
  • Distilled hydrothermal water around 60 ° C, about 20 times the weight is added to 50 g of the dried leaves of this morohea, sterilized by heating to 95 ° C or higher, cooled to 60 ° C, and then liquidized in a water bath. While maintaining the temperature at 60 ° C., 0.7% by weight of Protease Namano G (manufactured by Amano Enzyme Co., Ltd.) was dissolved in a small amount of water and added to the raw dried Moroheiya leaves. Thereafter, stirring was carried out every 10 minutes while maintaining the liquid temperature at 60 ° C.
  • Morohaya adsorbed fraction extract _Be (with protease treatment, with SP 207 adsorption treatment)
  • 80 cc of synthetic adsorbent SP 207 (manufactured by Mitsubishi Chemical Corporation) in a wet state in pure water was packed into a glass column, and sufficient pure water was passed through to form a SP 207 packed column. 1
  • the treated extract solution 30 OmL (Brix 1.2, pH 6.0) was passed through the glass column at the rate of SV-4, and then the moroheiya extract was sufficiently washed out with 10 bed volumes of pure water.
  • the column effluent was collected immediately after the start of the passage of the morohaya enzyme-treated extract solution, and used as a passing-through fraction.
  • 5 bed volumes of ethanol adjusted to 60% concentration were passed through.
  • the 1Z2 bed volume of column effluent was discarded, and then collection of the column effluent was started and collected until the end of the flow of ethanol. This was taken as an adsorption fraction.
  • the flow-through fraction and the adsorbed fraction were each concentrated under reduced pressure and then lyophilized to obtain a powdery flow-through fraction extract (Bel) 2.1 g and an adsorbed fraction extract (Be 2) 0.8 g Got.
  • Synthetic adsorbent SP 70 wet from pure water (Mitsubishi Chemical Co., aromatic synthetic adsorbent) 80 cc is packed into a glass column, and enough pure water is passed through to form an SP 70 packed column.
  • Morohaya leaves from which hard stems had been removed were steam-heated, crushed and dried with hot air to obtain dried Morrohair leaves.
  • Distilled hydrothermal water around 60 ° C, about 20 times the weight is added to 50 g of the dried leaves of this morohea, sterilized by heating to 95 ° C or higher, cooled to 60 ° C, and then liquidized in a water bath. The temperature was kept at 60 ° C., and 0.7% by weight of Samoaise Y10 (manufactured by Yamato Kasei) was dissolved in a small amount of water and added to the raw dried Moroheiya leaves. Thereafter, stirring was performed every 10 minutes while maintaining the liquid temperature at 60 ° C.
  • Synthetic adsorbent wet in pure water SP 207 (Mitsubishi Chemical Co., Ltd.) 1 500 cc is filled into a glass power ram, and sufficient pure water is passed through to form an SP 207 filling power ram.
  • the moroha leaf stalk from which the stem was removed was steam-branched, crushed into a puree, and stored frozen.
  • This frozen puree was thawed in running water, and 1.5 times the weight of distilled water (1500 g) was added to 1000 g of puree, and mixed uniformly with a juicer mixer.
  • ethanol adjusted to 60% concentration After discarding the 1/2 bed capacity column effluent, start collecting the column effluent and collect it until the end of the ethanol flow. This is the adsorption fraction.
  • the flow-through fraction and the adsorbed fraction were each concentrated under reduced pressure and then lyophilized to obtain 2.1 g of a flow-through fraction extract (Cel) and 0.9 g of an adsorbed fraction extract (C e 2).
  • Morohaya adsorbed fraction extract De2 (with enzyme treatment, with SP 850 adsorption treatment); synthetic resin adsorbent wet with pure water SP 850 (Mitsubishi Chemical Corporation, aromatic synthetic adsorbent) 80 cc glass column And add enough pure water to make an SP 850 packed column.
  • Spontaneous hypertensive rats were used to examine the antihypertensive effect after a single administration.
  • 1 Omg / kg of powdered morohea extract A, enzyme-treated extract B, enzyme-treated extract B, and enzyme-treated extract C obtained in Examples 1, 2, 3 and 5 before the adsorption treatment.
  • SHR body weight In water for injection, powders A, B, B, 17-week-old (male) for powder A, 18-week-old (male) spontaneously hypertensive rat (SHR / Ho) s, SPF) was administered orally using a gastric tube. Blood pressure was measured noninvasively before administration, 4 hours after administration, 8 hours, and 24 hours after administration. The number of animals used in the study is shown in the table below. In addition, although 7 mice were used for each group, data on individuals that clearly showed abnormal blood pressure fluctuations were deleted.
  • Figure 1 shows the changes in systolic blood pressure up to 24 hours after administration.
  • Figure 2 shows changes in diastolic blood pressure up to 24 hours after administration.
  • Figure 3 shows heart rate fluctuations up to 24 hours after administration. Dosing 2
  • Figure 4 shows the change in mean blood pressure up to 4 hours later.
  • Figure 5 shows the diurnal variation in systolic blood pressure of SHR up to 24 hours after administration.
  • Example 2 (B) and Example 3 (B ′) above the enzyme-treated extract obtained by treating molhaea leaves with a proteolytic enzyme does not undergo enzyme treatment. It exhibited a stronger blood pressure lowering effect than conventional extracts obtained from leaves. In each figure, each value represents an average value.
  • Figure 6 shows the changes in systolic blood pressure and diastolic blood pressure up to 24 hours after administration.
  • FIG. 9 shows the change in mean blood pressure up to 4 hours after administration of the protease-treated powder B (with enzyme treatment, without resin adsorption treatment) obtained in Example 2. From FIG. 8, it was shown that the adsorbed fraction showed a stronger blood pressure lowering action than the pass-through fraction, and that the effect persisted until 24 hours later. Compared with the results in Fig. 9, the adsorbed fraction has a continuous blood pressure lowering action and is superior in the blood pressure lowering action.
  • the yield was 6.4 times higher than that of the example without enzyme treatment.
  • the ratio of the adsorbed fraction to the soluble solid content (solution volume XB rix measured value ⁇ 1 0 0) calculated from the Bri x measured value of the solution subjected to each adsorption treatment is calculated by the following equation. .
  • Adsorbed fraction / (Amount of soluble solid content calculated from Brix measurement value) X 1 0 0 (%)
  • the ratio of these adsorbed fractions in this example is obtained when the enzyme treatment is not performed as a result of measurement.
  • Example 1 In Example 4, it was 10.7%, and in Example 4, it was 5.8%.
  • Example 2-3 On the other hand, when synthetic resin was adsorbed on the enzyme-treated ex, Example 2-3 was 19%, and Example 2-2 was 2 2.
  • Example 3_2 was 19.3%
  • Example 5 was 18.8%
  • Example 6 was 15.7%.
  • the solution filtered through No. 2 filter paper after solid-liquid separation was used to measure the adsorbed fraction obtained by this patented method by Brix measurement of the solution. It can be defined as a composition containing 15% or more of the soluble solid content calculated from the value (measured value of solution volume XB rix ⁇ 100).
  • the amount of the synthetic adsorbent to be used may be an amount that can sufficiently adsorb the adsorbing component in the solution to be passed, and preferably 1 Z 8 of the volume when the solution to be passed is Bri x 1%. Use more than double the amount of synthetic adsorbent.
  • the adsorbed fraction excellent in blood pressure lowering action was 0.29 g in the fraction extract A e of Example 1 that was not subjected to the protease treatment
  • the amount was 0.8 g, which was about 2.8 times higher in the case where the enzyme treatment was performed than in the case where the enzyme treatment was not performed.
  • the ratio of the adsorbed fraction to the total solid content (through fraction + adsorbed fraction) in each example was 10% with the fraction extract A e 2 of Example 1 and the fraction of Example 2 Minute extract B e 2 22.
  • the adsorbed fraction extract Be 2 of Example 2 was orally administered to 5-week-old male SHR / Hos once a day for 56 days for 90 mg mg Zkg (weight of SHR).
  • the control group was similarly given water for injection.
  • the results are shown in Figure 12. Each value represents an average value.
  • “*” indicates that there was a statistically significant difference at a risk rate of 5% or less compared to the control group.
  • “**” indicates that there was a statistically significant difference with a risk rate of 1% or less compared to the control group.
  • pentobarbital 50 mgZkg, ip
  • I I induction body surface electrocardiograms
  • angiotensin I changed to angiotensin I I by the action of angiotensin converting enzyme (ACE) in the living body, and increased blood pressure.
  • ACE angiotensin converting enzyme
  • Morohaya adsorbed fraction extract Be2 of Example 2 was further subjected to cation exchange treatment, and a further purified extract (see Example 7) obtained as the adsorbed fraction was administered into the duodenum (500 mgZkg).
  • Morohaya adsorbed fraction EX of the present invention has no conventionally reported ACE inhibitory activity. Therefore, further studies were conducted to elucidate the mechanism of blood pressure reduction.
  • a ring-like specimen was prepared using the thoracic aorta extracted from male SD rats, and the vascular tension was measured in oxygenated 37 ° C TVi'ode solution.
  • vasoconstriction Ph e O. 1 ⁇
  • phenylephrine a vasoconstrictor
  • Morohaya adsorbed fraction extract ⁇ e 2 of Example 2 100, 300, 1000, 3000 ⁇ g ZmL
  • the presence or absence of vasorelaxant action was observed.
  • the result is shown in FIG.
  • a similar experiment was also conducted on the extract used in 1 of Test Example 7 which was further purified. The results are shown in Fig. 15.
  • the tension when Phenylephrine was added was set to 100%, and the blood vessel was relaxed when the tension was lowered.
  • the moroheiya extract of the present invention showed a statistically significant relaxing action at 1000 g / mL or more. Therefore, it has been clarified that the action mechanism of the blood pressure lowering action of the moroheia adsorbed fraction extract of the present invention is based on the vasorelaxant action. This is new knowledge about moroha.
  • the moroheiya adsorbed fraction extract of the present invention showed a statistically significant relaxation effect from 1000 ⁇ gZ mL.
  • the further purified product showed a statistically significant relaxation effect from 500 ⁇ g / mL. Each value indicates the average soil standard error.
  • Extract R Extract S-1 Extract S-2 Extract T
  • Morohaya adsorbed fraction extract Be2 was prepared. After that, 28.4 g of the above adsorbent fraction was used to extract extract R (11.1) from the fraction with a large molecular weight by cation exchange column chromatography using PK 208 resin and gel filtration chromatography using HW40EC resin. 1 2 g), extract S-1 (3.48 g), extract S-2 (1.39 g), and extract T (1.36 g). When each of the fractions was compared for vasorelaxant action, S-2 and T were observed to have a strong vasorelaxant effect S. The results are shown in Fig. 17.
  • flavonoid derivatives such as isoquinolecitrin and hyalin perine peak. As detected. Adenine was detected in the S-2 fraction.
  • Drugs that dilate blood vessels such as hydralazine are known to have an increased reflex heart rate that accompanies a decrease in vascular resistance.
  • Increasing reflex heart rate leads to tachycardia, increased heart rate, intrathoracic distress, paradoxical blood pressure increase, palpitation, etc., leading to decreased patient quality of life and compliance with drug use.
  • Morohaya has the effect of relaxing excessively contracted blood vessels. Therefore, changes in the heart rate analogy at the time of administration of the further purified extract used in Test Example 7 were confirmed.
  • the heart rate at the time of administration of the further purified extract used in Test Example 7 was 426.33 B.
  • the amino acid increment that is, the amount of amino acids constituting the water-soluble protein can be confirmed, but it is higher in the adsorbed fraction. This means that most water-soluble proteins are separated into adsorbed fractions. I can say that.
  • the derived composition is a material that can be expected to have the functionality of these raw protein proteins.
  • the morohea synthetic resin adsorbed fraction composition of the present invention in particular, the morohea synthetic resin adsorbed fraction composition obtained by synthetic resin adsorbed fractionation of the morohea enzyme-treated extract solution is calculated by the following formula (A). It was revealed that each amino acid concentration satisfies all the requirements of the following formulas (1) to (3).
  • Amino acid increment Amino acid amount after acid hydrolysis Amino acid amount before monoacid hydrolysis
  • the amino acid increment is 0.5 mL of 6 N hydrochloric acid added to 2 mL of Moguchiha synthetic resin adsorbed fraction composition solution of any concentration, and autoclaved at 1 2 1 ° C for 3 hours. This means the increment of amino acid when the above treatment is performed.
  • G1y is 3 times or more of V a1 and G1y is 3 times or more of I1e;
  • Sej at least one amino acid selected from A1a and Leu Is V a 1
  • a test on vasorelaxant activity was conducted in item 2 of Test Example 7.
  • a ring-shaped specimen was prepared using the rat thoracic aorta and an oxygenated nutrient solution The following tests were conducted on the blood vessel relaxing action of the resin-adsorbed fraction extract of the present invention by measuring the blood vessel tension. ⁇
  • phenylephrine as a vasoconstrictor was added to a concentration of 0.1 ⁇ M to constrict the blood vessels, and then the Morohella adsorbed fraction extract B e obtained in Example 2 above was used. 2 was added to the nutrient solution at 0.5 mg / ml, 1.0 mg / ml, 2.5 mg / ml, and 5.0 mg / ml, and observed for vasodilatory effect. (N 2 6).
  • L-NAME means L-NAME + Phenerpheline + Morroheia Extract B e
  • domethacin means Indomethacin + Phenylephrine + Morroheia Extract B e 2.
  • Morohaya adsorbed fraction extract B e 2 exhibited a vasorelaxing effect in a statistically significant and concentration-dependent manner from 0.5 mg / ml.
  • Pretreatment with indomethacin (PGI 2 inhibitor) did not affect the vasorelaxation response of Morohaya adsorbed fraction extract B e 2.
  • PKI 2 inhibitor indomethacin
  • L-NAME depression of NO production
  • Morohaya adsorbed fraction extract B When the same operation was performed using a blood vessel from which the endothelium had been removed, Morohaya adsorbed fraction extract B The change in the concentration-response curve of vasorelaxation due to e 2 is the same as when L-NAME was pretreated.
  • the moroheia adsorbed fraction extract of the present invention exerts an effect even in a state where the vascular endothelium function is reduced and relaxes the blood vessel. It can be administered safely to hypertensive patients with cardiovascular diseases such as sclerosis. Industrial applicability
  • the morohea adsorbed fraction extract of the present invention i.e., morohea synthetic resin adsorbed fraction composition
  • morohea adsorbed fraction extract of the present invention does not contain nicotinamine having ACE inhibitory activity, which has been conventionally known to be contained in morohaya, as an active ingredient, and has a vasorelaxant action as an action mechanism. This is completely different from the conventional product, and its effect is expected.

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Abstract

L'invention concerne une composition de fraction adsorbée sur une résine synthétique dérivée de jute tossa (Corchorus oitorius L.) présentant une excellente activité d'hypotenseur, en particulier une excellente activité d'anti-hypertenseur, qui peut être produite par soumission d'une solution d'extrait de jute tossa à un traitement d'adsorption au moyen d'un adsorbant de résine sysnthétique qui élue la fraction adsorbée au moyen d'un solvant d'élution et recueille la fraction adsorbée. La composition de fraction adsorbée sur une résine synthétique dérivée de jute tossa permet d'obtenir : un agent hypotenseur efficace pour traiter un patient souffrant d'hypertension, ne produisant pas d'effet secondaire indésirable et très sûr; un aliment, tel qu'un aliment naturel, un additif nutritionnel et un aliment pour des utilisations de santé spécifiées comprenant la composition; ou une boisson comprenant la composition de fraction adsorbée.
PCT/JP2008/069817 2007-10-31 2008-10-24 Composition de fraction adsorbée sur une résine synthétique dérivée de jute tossa à activité d'hypotenseur, agent hypotenseur ou aliment/boisson comprenant la composition de fraction adsorbée et procédé de production de la fraction adsorbée WO2009057724A1 (fr)

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2010270069A (ja) * 2009-05-22 2010-12-02 Ito En Ltd モロヘイヤ抽出物を有効成分とする血管病治療予防剤、及びこれを含有する飲食品

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JP2002363075A (ja) * 2001-06-05 2002-12-18 Kao Corp 高血圧症予防・治療剤
JP2006241006A (ja) * 2005-03-01 2006-09-14 Kao Corp クロロゲン酸類組成物の製造方法

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JP2002363075A (ja) * 2001-06-05 2002-12-18 Kao Corp 高血圧症予防・治療剤
JP2006241006A (ja) * 2005-03-01 2006-09-14 Kao Corp クロロゲン酸類組成物の製造方法

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AZUMA K. ET AL.: "Yasairui no Kosanka Kassei no Hyoka Oyobi Moroheiya ni Okeru Kassei Seibun no Dotei", YASAI CHAGYO KENKYU SEIKA JOHO, vol. 1998, 1999, pages 7 - 8 *
KIMOTO K. ET AL.: "Purification and Identification of Angiotensin I-Converting Enzyme Inhibitor from Morokheiya (Corchorus olitorius).", FOOD SCI TECHNOL INT TOKYO, vol. 4, no. 3, 1998, pages 223 - 226 *
KOKEAN Y. ET AL.: "Kennai Norin Suisanbutsu Koso Bunkaibutsu no Nyusankin Seiiku eno Eikyo to sono Hakkoeki no ACE Kassei Sogai ni Tsuite", MIE PREFECTURAL SCIENCE AND TECHNOLOGY PROMOTION CENTER KOGYO KENKYUBU KENKYU HOKOKU, vol. 31, 15 October 2007 (2007-10-15), pages 152 - 154 *
LASKAR S. ET AL.: "Extraction and chemical investigation of jute (Corchorus olitorius, Linn.) seed protein", APPL BIOCHEM BIOTECHNOL, vol. 14, no. 3, 1987, pages 253 - 257 *

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2010270069A (ja) * 2009-05-22 2010-12-02 Ito En Ltd モロヘイヤ抽出物を有効成分とする血管病治療予防剤、及びこれを含有する飲食品

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