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WO2012115026A1 - Composition contenant du tomatoside a - Google Patents

Composition contenant du tomatoside a Download PDF

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Publication number
WO2012115026A1
WO2012115026A1 PCT/JP2012/053934 JP2012053934W WO2012115026A1 WO 2012115026 A1 WO2012115026 A1 WO 2012115026A1 JP 2012053934 W JP2012053934 W JP 2012053934W WO 2012115026 A1 WO2012115026 A1 WO 2012115026A1
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WO
WIPO (PCT)
Prior art keywords
tomatoside
cholesterol
tomato
composition
acceptable salt
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/JP2012/053934
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English (en)
Japanese (ja)
Inventor
孝雄 山中
木下　恵美子
小幡　明雄
式久 高田
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Kikkoman Corp
Nippon Del Monte Corp
Original Assignee
Kikkoman Corp
Nippon Del Monte Corp
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Kikkoman Corp, Nippon Del Monte Corp filed Critical Kikkoman Corp
Priority to JP2013501017A priority Critical patent/JP6042800B2/ja
Publication of WO2012115026A1 publication Critical patent/WO2012115026A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • 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)
    • A61K36/81—Solanaceae (Potato family), e.g. tobacco, nightshade, tomato, belladonna, capsicum or jimsonweed
    • 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
    • A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
    • 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
    • A61P3/06—Antihyperlipidemics

Definitions

  • the present invention relates to a composition for preventing or treating a disease associated with dyslipidemia, which contains tomatoside A which is a saponin derived from tomato seeds or a physiologically acceptable salt thereof, and a method for producing the same.
  • the present invention also relates to a cholesterol elevation inhibitor, a triglyceride elevation inhibitor, and a liver cholesterol accumulation inhibitor containing tomatoside A or a physiologically acceptable salt thereof.
  • Dyslipidemia causes various diseases such as arteriosclerotic diseases.
  • arteriosclerotic diseases cardiovascular diseases, especially myocardial infarction, and deaths from cerebrovascular disorders, mainly cerebral infarction and stroke, occupy a large position alongside cancer. About 30%.
  • the risk is expected to increase further with the rapid transition to an aging society.
  • Non-patent Document 1 a food ingredient having a cholesterol-lowering action or a cholesterol-rising-inhibiting action so far, dietary fiber Plant sterols, saponins, phospholipids, soybean proteins, and the like have been reported (for example, see Non-patent Document 1).
  • tomatoes are the most cultivated vegetables, are eaten widely all over the world, and contribute greatly to improving people's health.
  • Tomatoes contain many types of functional nutrients such as dietary fiber (cellulose, pectin, etc.) and have been studied for many years.
  • Lycopine a representative carotenoid contained in tomato, is known to have strong antioxidant activity, reducing the risk of developing prostate cancer, pancreatic cancer, lung cancer, normalizing liver function, preventing myocardial infarction, Effects such as cataract prevention have been reported.
  • naringenin chalcone which is a kind of polyphenol present in tomato peel, suppresses type I allergy represented by nasal allergy such as hay fever (see, for example, Non-Patent Documents 2 and 3).
  • ⁇ -tomatine As a component contained in tomato, the presence of alkaloid glycoside called ⁇ -tomatine is known in immature tomato fruit although it is a trace amount.
  • ⁇ -Tomatine has 1 molecule of xylose, 2 molecules of glucose, and 1 molecule of galactose bound to tomatidine, which is a steroidal glycoside, and its concentration decreases as the fruit matures.
  • ⁇ -Tomatine has a characteristic of forming an insoluble complex with cholesterol, and there is a report that it decreases LDL cholesterol level which is bad cholesterol in a feeding test to hamster (for example, see Non-patent Document 4).
  • Patent Document 1 discloses prevention and treatment of arteriosclerosis containing tomatidine obtained from the above-ground part of tomato (stem, leaf, etc.) after harvesting tomato fruit as an active ingredient.
  • Agents, blood cholesterol lowering agents and macrophage foaming inhibitors are disclosed.
  • Patent Document 2 discloses a plasma triglyceride concentration lowering effect of a water-soluble tomato extract or a fraction thereof that does not contain lycopene and does not contain water-insoluble particulate matter.
  • tomatoside A which is a kind of saponin, is a component that is very much present in tomato seeds (the jelly part containing the seeds) (see, for example, Non-Patent Document 6), and is known to have a surface-active effect. (For example, refer nonpatent literature 5). However, there has been no report on physiological activity due to components contained in tomato seeds.
  • An object of the present invention is to provide a composition for preventing or treating dyslipidemia such as hypercholesterolemia or hypertriglyceridemia and diseases related thereto.
  • Another object of the present invention is to provide any one or more of a cholesterol elevation inhibitor, a triglyceride elevation inhibitor, and a liver cholesterol accumulation inhibitor.
  • the present inventors have intensively studied and tomatoside A separated from the squeeze cake generated when producing the juice of tomato fruit used for tomato juice, tomato puree, tomato paste, etc. Has been found to suppress the increase in blood lipid levels such as cholesterol and triglyceride and suppress the accumulation of cholesterol in the liver. Moreover, the tomato processed food / beverage products containing this tomatoside A discovered that said effect
  • the present invention is as follows: [1] Cholesterol elevation inhibitor containing tomatoside A or a physiologically acceptable salt thereof; [2] Triglyceride elevation inhibitor containing tomatoside A or a physiologically acceptable salt thereof; [3] An inhibitor of hepatic cholesterol accumulation containing tomatoside A or a physiologically acceptable salt thereof; [4] A composition for preventing or treating a disease associated with dyslipidemia, comprising tomatoside A or a physiologically acceptable salt thereof; [5] The agent or composition according to any one of [1] to [4], wherein the content of the tomatoside A or a physiologically acceptable salt thereof is 0.001 to 80% by weight; [6] A tomato processed food or drink containing the agent or composition according to any one of [1] to [4], wherein the content of the tomatoside A or a physiologically acceptable salt thereof is 0.001-80% by weight tomato processed food and drink; [7] A composition comprising tomatoside A or a physiologically acceptable salt thereof, comprising a step of extracting
  • the present invention also relates to the following method: [9] A method for suppressing cholesterol elevation, comprising a step of administering an effective amount of tomatoside A or a physiologically acceptable salt thereof; [10] A method for suppressing an increase in triglyceride, comprising a step of administering an effective amount of tomatoside A or a physiologically acceptable salt thereof; [11] A method of inhibiting hepatic cholesterol accumulation, comprising the step of administering an effective amount of tomatoside A or a physiologically acceptable salt thereof; and [12] an effective amount of tomatoside A or a physiologically acceptable salt thereof.
  • a method for preventing or treating a disease associated with dyslipidemia comprising a step of administering.
  • a composition for preventing or treating dyslipidemia such as hypercholesterolemia or hypertriglyceridemia and a disease related thereto, a cholesterol elevation inhibitor, a triglyceride elevation inhibitor, and hepatic cholesterol accumulation
  • dyslipidemia such as hypercholesterolemia or hypertriglyceridemia and a disease related thereto
  • a cholesterol elevation inhibitor such as hypercholesterolemia or hypertriglyceridemia and a disease related thereto
  • a cholesterol elevation inhibitor such as hypercholesterolemia or hypertriglyceridemia and a disease related thereto
  • a cholesterol elevation inhibitor such as hypercholesterolemia or hypertriglyceridemia and a disease related thereto
  • a cholesterol elevation inhibitor such as hypercholesterolemia or hypertriglyceridemia and a disease related thereto
  • a triglyceride elevation inhibitor such as a triglyceride elevation inhibitor
  • hepatic cholesterol accumulation any one or more of the inhibitors
  • the composition and the agent can be easily and efficiently separated
  • Tomatoside A (tomatoside A, tomatoside A), which is an active ingredient of the composition and agent of the present invention (hereinafter also simply referred to as “the composition of the present invention”), is a compound having the following structure.
  • Tomatoside A is a kind of saponin and is a water-insoluble compound known to be contained in a large amount in tomato seeds.
  • physiologically acceptable salts of tomatoside A which is an active ingredient in the composition of the present invention, include sodium salts and potassium salts of compounds having the above-mentioned structure. It is not particularly limited as long as it is an acceptable salt.
  • tomatoside A and / or a physiologically acceptable salt thereof is also simply referred to as “tomatoside A”.
  • a chemically synthesized product may be used, but more simply, a tomato fruit-derived product containing tomato seeds is used as an extraction solvent by using 10% by volume or more and less than 90% by volume of an organic solvent.
  • a composition containing tomatoside A can be obtained. The method will be described in detail below.
  • the tomato fruit-derived material as a raw material is not particularly limited as long as it contains tomato seeds, but it is preferable to consider that the shape and quantity of seeds differ depending on the variety and maturity of tomato.
  • the squeeze cake obtained in the process of obtaining the squeezed solution of tomato fruit is generally discarded or used as a livestock feed. Since the composition containing A can be obtained easily and efficiently, it is preferable.
  • the tomato juice squeezed solution used for tomato juice, tomato puree, tomato paste, etc. is obtained by washing the tomato fruit in a conventional manner, crushing it, preheating it, and then squeezing it. In the process of squeezing, about 1 to 5% of the fruit is generated as squeezed straw.
  • Juice lees are mainly composed of pericarp and seeds, which are not only rich in fiber such as pectin, which is a water-soluble dietary fiber, but also cellulose and hemicellulose, which are water-soluble dietary fibers, as well as polyphenols, Saponins also remain.
  • pectin which is a water-soluble dietary fiber
  • cellulose and hemicellulose which are water-soluble dietary fibers, as well as polyphenols, Saponins also remain.
  • the above-mentioned tomato fruit-derived material is extracted using an extraction solvent using a method known to those skilled in the art, for example, as described in Examples below.
  • the tomato fruit-derived product is preferably a dried product.
  • the extraction solvent is not particularly limited as long as it is an organic solvent that can be an extraction solvent for food additives.
  • One or more organic solvents can be used.
  • ethanol (10 to 90% by volume), methanol (10 to 90% by volume), 1-butanol (30 to 90% by volume) and hexane (5% by volume 70) are preferable.
  • An organic solvent selected from less than volume%) can be used, and most preferably ethanol can be used.
  • an ethanol solvent of 10% by volume or more and less than 90% by volume can be used as the extraction solvent, preferably an ethanol solvent of 30% by volume or more and 70% by volume or less can be used, and more preferably about 70% by volume.
  • An ethanol solvent can be used.
  • the 70% by volume ethanol solvent refers to a mixture of ethanol and water in a volume ratio of 7: 3.
  • the pH of the extraction solvent is not particularly limited as long as tomatoside A is extracted, but is preferably not strongly acidic from the viewpoint of extraction efficiency, and is preferably pH 4 or more, more preferably pH 5 or more.
  • the temperature at the time of extraction is not particularly limited as long as tomatoside A is extracted, but from the viewpoint of extraction efficiency, it is preferably 0 ° C. or higher and lower than 55 ° C., more preferably 5 ° C. or higher and 40 ° C. or lower. From the viewpoint of workability, it is particularly preferable to perform extraction at around 25 ° C., which is about room temperature.
  • Extraction time is not particularly limited as long as tomatoside A is extracted, but is preferably 30 minutes or more and more preferably 1 hour or more and 2 hours or less from the viewpoint of extraction efficiency and workability. Extraction can be carried out by any method of stationary extraction and stirring extraction, but from the viewpoint of extraction efficiency, stirring extraction is preferably performed.
  • the number of extractions is not particularly limited as long as tomatoside A is extracted, and for example, extraction can be performed about 1 to 3 times.
  • extraction is performed at room temperature for 1 hour using 70% by volume ethanol solvent as an extraction solvent, A sufficient extraction can be achieved with one or two extractions.
  • the extract obtained by removing the residue by filtration can be subjected to concentration under reduced pressure or lyophilization by a conventional method to obtain a composition containing tomatoside A.
  • the composition thus obtained can contain, in addition to tomatoside A, saponins other than polyphenols and tomatoside A contained in the raw material derived from tomato fruit.
  • the obtained composition may be further purified, for example, by chromatography or the like, if necessary. Whether tomatoside A is contained in the obtained composition can be confirmed by a conventional method such as HPLC using a standard product.
  • the obtained composition may be used as it is as the composition of the present invention, or it may be used as it is or in a purified product in the following pharmaceuticals and foods and drinks.
  • tomatoside A exhibits cholesterol adsorption activity in vitro, and suppresses blood lipid level increase by cholesterol loading in vivo (particularly, serum total cholesterol increase suppression, serum non-HDL, Cholesterol elevation-inhibiting action and serum triglyceride elevation-inhibiting action) and hypercholesterolemia caused by cholesterol load.
  • This action is highly effective even compared with soybean saponin, which has been known to have a cholesterol lowering action. Moreover, it has the effect
  • the composition containing tomatoside A can be used as a cholesterol elevation inhibitor (particularly a blood cholesterol elevation inhibitor), a triglyceride elevation inhibitor or a liver cholesterol accumulation inhibitor.
  • cholesterol means “blood cholesterol”.
  • a composition containing tomatoside A is used for the prevention or treatment of a disease associated with dyslipidemia, for example, a disease associated with hypercholesterolemia or hypertriglyceridemia, or a condition associated with dyslipidemia. It can be used as a composition for prevention or improvement.
  • These agents and compositions can be administered to animals including humans as they are, and can be used by blending them with pharmaceuticals (pharmaceutical compositions) and foods and drinks.
  • a method for inhibiting cholesterol elevation a method for inhibiting elevation of triglyceride, a method for inhibiting hepatic cholesterol accumulation, and prevention of diseases associated with dyslipidemia, comprising the step of administering an effective amount of tomatoside A
  • a method of treatment can be provided.
  • diseases and conditions associated with dyslipidemia include diseases associated with hypercholesterolemia, diseases associated with high LDL cholesterolemia, diseases associated with hypertriglyceridemia, and the like. More specifically, arteriosclerosis, arteriosclerotic angina, ischemic heart disease such as myocardial infarction, cerebral infarction, stroke cerebral thrombosis, cerebral hemorrhage, cerebrovascular disease such as subarachnoid hemorrhage, pancreatitis, etc. Can be mentioned.
  • composition of the present invention having the above action is used in combination with other foods and active ingredients known to have an effect on dyslipidemia such as hypercholesterolemia, high LDL cholesterolemia, and hypertriglyceridemia.
  • dyslipidemia such as hypercholesterolemia, high LDL cholesterolemia, and hypertriglyceridemia.
  • an additive effect or a synergistic effect can also be obtained.
  • Such foods and active ingredients include various dietary fibers (low molecular sodium alginate, psyllium, pectin, wheat bran, lignin, etc.), tea catechins, chitosan, various plant sterols, various saponins (soy saponins, alfalfa saponins, Yucca saponin, ginseng saponin, chickpea saponin, etc.), various phospholipids, soybean protein, natural amino acids derived from cabbage or broccoli, various fatty acids (13-oxo-9,11-octadecadienoic acid, etc.) and the like.
  • various dietary fibers low molecular sodium alginate, psyllium, pectin, wheat bran, lignin, etc.
  • tea catechins chitosan
  • various plant sterols various saponins (soy saponins, alfalfa saponins, Yucca saponin, ginseng saponin, chic
  • composition of the present invention and foods and beverages and pharmaceuticals containing the composition are preferably 0.001 to 80% by weight, more preferably 0.005 to 60% by weight, particularly preferably tomatoside A as an active ingredient, in terms of dry weight. Contains 0.005 to 0.6% by weight. If the tomatoside A content is too low, the desired effect may not be obtained. Moreover, when mix
  • a pharmaceutical preparation can be obtained by adding a pharmaceutically acceptable excipient.
  • Pharmaceutical preparations include tablets, capsules, granules, fine granules, powders, liquids, syrups, chews, lozenges and other oral preparations, ointments, gels, creams, patches, external preparations, injections,
  • the dosage form can be a sublingual, inhalant, eye drop, suppository or the like.
  • a preferred dosage form is an oral preparation.
  • the dose of the composition of the present invention can be appropriately set according to the target disease and condition, the degree of the disease, the age, weight, etc. of the subject. It is possible to administer about 1 to 1000 mg / kg body weight, preferably about 0.4 to 200 mg / kg body weight. Administration may be performed in a single dose or divided into several doses.
  • the administration route of the composition of the present invention is not particularly limited, but can be conveniently administered by oral administration.
  • the composition of the present invention can be preferably mixed with food and drink.
  • the food and drink include supplements, foods for specified health use, functional nutritional foods, health foods, functional foods, health supplements, and normal foods and drinks.
  • examples of shapes include liquids such as juices, soft drinks, drinks, and tea, solids such as biscuits, tablets, granule powders, powders, and capsules, and semi-fluid forms such as pastes, jellies, soups, seasonings, and dressings. . Any of these foods and drinks can be produced by adding tomatoside A using methods known to those skilled in the art.
  • the above-mentioned food and drink have blood cholesterol elevation inhibitory effect, blood triglyceride elevation inhibitory effect, liver cholesterol accumulation inhibitory effect, dyslipidemia preventive action, dyslipidemia improving action, lifestyle-related disease preventive action, lifestyle-related disease improving action
  • subjected the display to the effect, such as, may be sufficient.
  • tomatoside A is 0.1 to 200 mg / day, preferably 10 to 150 mg / day, more preferably 20 to About 100 mg / day can be taken.
  • the number of intakes is not particularly limited, but is preferably 1 to 3 times a day, and the number of intakes may be increased or decreased as necessary.
  • composition of the present invention when blended with processed tomato foods and drinks, even when tomatoside A is added, the tomato feeling and richness are not impaired, and the flavor is impaired as compared with processed tomato foods and foods without adding tomatoside A. No tomato processed food or drink.
  • blended tomatoside A have a higher blood cholesterol raise inhibitory effect compared with the case where only tomatoside A is administered.
  • active ingredients for example, lycopene, ⁇ -tomatine, escleoside A and B, dietary fiber (cellulose, pectin, etc.), various polyphenols, etc.
  • the composition of the present invention can be preferably blended in tomato processed foods and drinks.
  • tomato processed foods and drinks include tomato juice, tomato mix juice, tomato ketchup, tomato sauce, chili sauce, tomato juice drink, solid tomato, tomato puree, tomato paste, tomato soup and the like.
  • These tomato processed food / beverage products are prepared according to the normal manufacturing method, respectively, adding the composition of this invention containing tomatoside A according to the manufacturing method (recipe etc.) of normal tomato processed food / beverage products.
  • tomato processed foods and drinks have seeds removed during the production process, and tomatoside A is hardly detected.
  • the present inventors have confirmed that when the tomatoside A content in tomato juice was measured by the HPLC method described in Example 1-1 described later, it was below the detection limit.
  • the tomatoside A content in tomato juice was considered to be 0.0005% by weight or less.
  • Example 1 extraction of Tomato Cide A from Tomato Juice 1-1. Examination of extraction solvents Brushed ripe tomato fruits for processing, crushed with a chopper, preheated with an indirect tube heater, and squeezed with a pulper finisher to obtain a juice . The squeezed rice cake generated in the squeezing process was freeze-dried and further pulverized to obtain a dried product of tomato squeeze rice cake containing tomato seeds. To 20 g of the obtained dried product, 1,000 mL of each extraction solvent shown in Table 1 was added, followed by stirring and extraction under a temperature condition of 25 ° C. for 2 hours, followed by filtration. The obtained extract was concentrated under reduced pressure to obtain a tomatoside A extract.
  • 10 volume% ethanol (a mixture of water and ethanol in a volume ratio of 9: 1), 30 volume% ethanol (a mixture of water and ethanol in a volume ratio of 7: 3), 50 volume% ethanol (a mixture of water and ethanol) (5: 5 volume ratio mixture), 70 volume% ethanol (water / ethanol volume ratio 3: 7 mixture), 90 volume% ethanol (water / ethanol volume ratio 1: 9 mixture), 0.1% acetic acid Added 70 volume% ethanol (mixture of water, ethanol and acetic acid in a volume ratio of 3: 7: 0.01), 1% acetic acid added 70 volume% ethanol (water, ethanol and acetic acid in a volume ratio of 3: 7: 0. Table 1 shows the relative concentration of tomatoside A in each extract when the mixture of 1) is used. The relative concentration was calculated by the method described below.
  • the mobile phase A solution was distilled water, the B solution was an acetonitrile solution, the sample injection amount was 10 ⁇ L, and the detection was performed with an evaporative light scattering detector (model ELSD-LTII, manufactured by Shimadzu Corporation). After the measurement, the relative concentration of tomatoside A under each extraction condition was calculated with the tomatoside A content of the extract concentrate with 70% by volume ethanol showing the highest extraction efficiency as 100.
  • a tomatoside A-containing preparation was produced from the dried tomato juice cake containing tomato seeds under the extraction conditions optimized based on the results of 1-1 to 1-4 above. .
  • 1000 mL of 70 volume% ethanol was added as an extraction solvent, followed by stirring and extraction at room temperature for 2 hours, followed by filtration.
  • the residue after filtration was further subjected to the same extraction treatment once, and the obtained two extracts were combined and concentrated under reduced pressure to obtain a tomatoside A crude extract.
  • the obtained crude extract was adsorbed on reversed-phase column chromatography (YMC-ODS-A, manufactured by YMC) and obtained by eluting sequentially with water, 40% by volume methanol, 70% by volume methanol, and 100% by volume methanol.
  • the elution fraction was freeze-dried to obtain a tomatoside A-containing preparation containing 60% by weight of tomatoside A.
  • Example 2 (Sensory evaluation of tomato juice containing tomatoside A) Tomato juice to which the preparation containing 60% by weight of tomatoside A obtained in Example 1-5 was added in the amount shown in Table 5 (0 mg to 20 mg / 100 g in terms of added amount of tomatoside A) (no added salt) The sensory evaluation by eight panelists was performed regarding tomato feeling, richness and bitterness. Tomato juice to which no tomatoside A is added (control), the tomato feeling, richness and bitterness intensity are evaluated in 7 stages, when the tomato feeling, richness and bitterness intensity are 4 out of 7 stages, The average of the evaluation of 8 panelists was calculated. The results are shown in Table 5. Even if tomatoside A was added, the tomato feeling and richness of tomato juice were not impaired, and it became a tomato processed food and drink that was inferior to tomato juice without adding tomatoside A.
  • Example 3 Cholesterol adsorption ability of tomatoside A-containing composition
  • Cholesterol adsorption ability of tomatoside A was measured in an in vitro system.
  • a preparation containing 60% by weight of tomatoside A obtained in Example 1-5 was dispersed in 1 mL of pH 7.5 phosphate buffer at a dose shown in Table 6, and 0.5% by weight cholesterol (special grade cholesterol) was added thereto.
  • cholesterol special grade cholesterol
  • Manufactured by Wako Pure Chemical Industries, Ltd. was added in an amount of 0.01 mL, stirred well, and then heated at 37 ° C. for 2 hours.
  • the tomatoside A preparation exhibited a dose-dependent cholesterol adsorption activity, similar to soybean saponin, which is conventionally known to have a cholesterol-lowering effect. Moreover, when cholesterol adsorption ability was similarly measured using the tomatoside A purified product, cholesterol adsorption activity was shown as in the above preparation.
  • Example 4 Long-term administration of tomatoside A-containing composition to mice 1
  • Test feeds in which cholesterol (special grade cholesterol, manufactured by Wako Pure Chemical Industries) and sodium cholate (sodium cholate, manufactured by Wako Pure Chemical Industries) were added to MF powder feed (produced by Oriental Yeast Co., Ltd.) are shown in Table 7 below.
  • a mixed diet prepared by blending and further containing a preparation containing 60% by weight of tomatoside A obtained in Example 1-5 (containing 0.33 to 1.0% by weight in terms of tomatoside A) was given to mice. The effect on blood lipid concentration when administered was confirmed.
  • a mixed diet supplemented with soy saponin was administered to mice.
  • mice Twenty-four 5-week-old male C57BL6 / J mice (manufactured by CLEA Japan, Inc.) were preliminarily raised for 1 week on an MF powder feed, and then divided into 4 groups of 6 control groups and 1 to 4 administration groups. .
  • the control group 1 and the administration groups 2 to 4 were each bred for 3 weeks with the test feed shown in Table 7. The feed was administered by free consumption.
  • Blood was collected before administration of the test feed (after 0 days) and 3, 7, 10, 14, and 21 days after the start, and total serum cholesterol was measured.
  • serum HDL cholesterol and serum neutral lipid were measured 21 days after the start of administration.
  • the measurement was performed using cholesterol E test Wako, HDL cholesterol test Wako, and triglyceride test Wako (manufactured by Wako Pure Chemical Industries, Ltd.) according to the respective instructions for use.
  • the non-HDL cholesterol level was determined by calculating the total cholesterol-HDL cholesterol level.
  • the arteriosclerosis index was obtained by calculating the value of (total cholesterol-HDL cholesterol) / HDL cholesterol.
  • Table 8 shows the measurement results of serum total cholesterol
  • Table 9 shows the measurement results of non-HDL cholesterol
  • Table 10 shows the measurement results of serum triglyceride
  • Table 11 shows the measurement results of arteriosclerosis index.
  • test group 3 and test group 4 As shown in Table 8, the serum total cholesterol of test group 3 and test group 4 mixed with a preparation containing 60% by weight of tomatoside A was lower than that of control group 1 and test group 2 mixed with soybean saponin. Indicated. As shown in Table 9, the test group 3 and the test group 4 also showed lower values than the control group 1 and the test group 2 for the non-HDL cholesterol level. From the results in Table 9, it was considered that administration of soybean saponin (test group 2) had no effect on the amount of non-HDL cholesterol. As shown in Table 10, test group 3 and test group 4 also showed lower values for serum neutral lipid than control group 1 and test group 2. Furthermore, as shown in Table 11, also about the arteriosclerosis index, the test group 3 and the test group 4 showed a significantly low value compared with the control group 1, and also showed a low value compared with the test group 2.
  • tomatoside A has an action of suppressing an increase in blood lipid concentration due to cholesterol loading, and further has an action of lowering arteriosclerosis index (an action to reduce the risk of arteriosclerosis) accompanying this action. Became clear. Moreover, it became clear that the effect
  • Example 5 Cholesterol adsorption ability of tomatoside A and / or tomato juice composition
  • Cholesterol adsorption ability by the composition of tomatoside A and tomato juice was measured in an in vitro system.
  • a preparation containing 60% by weight of tomatoside A obtained in Example 1-5 and a dried tomato juice powder obtained by lyophilizing commercially available salt-free tomato juice were prepared at pH 7.
  • Example 6 Long-term administration of tomatoside A and / or tomato juice composition to mice
  • Table 13 below shows test feeds in which cholesterol (special grade cholesterol, manufactured by Wako Pure Chemical Industries) and sodium cholate (sodium cholate, manufactured by Wako Pure Chemical Industries) were added to MF powdered feed (produced by Oriental Yeast Co., Ltd.).
  • Preparations containing 60% by weight of tomatoside A prepared in Example 1-5 and tomato juice dry powder obtained by freeze-drying commercially available salt-free tomato juice were shown in Table 13, respectively.
  • the effect on blood lipids was confirmed when a mixed diet added in step 1 was administered to mice.
  • mice Twenty-four 5-week-old male C57BL6 / J mice (produced by CLEA Japan) were preliminarily raised on MF powder diet for 1 week, and then divided into 4 groups of 5 control groups and 6 to 8 test groups. .
  • Control group 5 and test groups 6-8 were each bred for 2 weeks on the test feed shown in Table 13. The feed was administered by free consumption. Blood was collected before administration of the test feed (after 0 days) and 3, 9, and 14 days after the start, and total serum cholesterol was measured. The measurement was performed using cholesterol E test Wako (manufactured by Wako Pure Chemical Industries, Ltd.).
  • Table 14 shows the measurement results of serum total cholesterol. Serum of test group 6 fed with 0.034% by weight of a preparation containing 60% by weight of tomatoside A (0.02% by weight in terms of tomatoside A) and test group 7 fed with 5% by weight of dried tomato juice powder Total cholesterol was lower than that of Control Group 5. In addition, the total serum cholesterol of test group 8 in which 0.034% by weight of a preparation containing 60% by weight of tomatoside A (0.02% by weight in terms of tomatoside A) and 5% by weight of frozen tomato juice powder was simultaneously fed In both 9 and 14 days after the start of administration, the values were lower than those in the control group 5 and the test groups 6 and 7.
  • the tomatoside A preparation and the tomato juice frozen powder have an action of suppressing an increase in blood lipid concentration due to cholesterol loading, and the tomatoside A preparation and the tomato juice frozen powder are mixed and administered, whereby the tomatoside A preparation is prepared. It became clear that it shows a strong effect
  • Example 7 Long-term administration of tomatoside A-containing composition to mice 2
  • Table 15 shows test feeds in which cholesterol (special grade cholesterol, manufactured by Wako Pure Chemical Industries) and sodium cholate (sodium cholate, manufactured by Wako Pure Chemical Industries) were added to MF powdered feed (produced by Oriental Yeast Co., Ltd.).
  • cholesterol special grade cholesterol, manufactured by Wako Pure Chemical Industries
  • sodium cholate sodium cholate, manufactured by Wako Pure Chemical Industries
  • Serum HDL cholesterol was measured 0 and 21 days after the start of administration. 21 days after the start of administration, the liver of each mouse was excised, the total lipid in the liver was extracted by the Folch method, and the total cholesterol was measured. The measurement was performed using Cholesterol E Test Wako, HDL Cholesterol Test Wako, and Triglyceride E Test Wako (manufactured by Wako Pure Chemical Industries, Ltd.) according to the respective instructions for use. The non-HDL cholesterol level was determined by calculating the total cholesterol-HDL cholesterol level.
  • the arteriosclerosis index was obtained by calculating the value of (total cholesterol-HDL cholesterol) / HDL cholesterol.
  • the measurement results of serum total cholesterol are shown in Table 17, the measurement results of non-HDL cholesterol are shown in Table 18, the measurement results of arteriosclerosis index are shown in Table 19, and the measurement results of liver total cholesterol are shown in Table 20, respectively.
  • the serum total cholesterol of test group 11 fed with a preparation containing 60% by weight of tomatoside A was lower than the value before the start of administration, and showed a significantly lower value 21 days after the start of administration. . Moreover, it became a value equivalent to the serum cholesterol of the control group 10 transferred to the normal feed from the high cholesterol feed.
  • the non-HDL cholesterol level 21 days after the start of administration was significantly lower in the control group 10 and the test group 11 than in the control group 9.
  • the control group 10 and the test group 11 showed the high value compared with the control group 9 in the HDL cholesterol ratio which occupies for total cholesterol.
  • the arteriosclerosis index was also significantly lower in the control group 10 and the test group 11 than in the control group 9.
  • tomatoside A has an action of improving hypercholesterolemia caused by cholesterol load and reducing the risk of arteriosclerosis.
  • Example 8 Manufacture of tomato processed foods and drinks containing tomatoside A
  • the manufacture example of the tomato processed food-drinks which uses tomatoside A as a part of raw material below is shown.
  • Tomato Juice Season packed tomato juice production methods include tomato washing, sorting, crushing, heating, squeezing, blending, degassing, sterilizing, filling, cooling and boxing processes.
  • Tomatoside A was added to the mixture, and salt was added only in the case of salt, mixed with nitrogen gas, degassed under reduced pressure, the dissolved oxygen concentration was reduced to 3 ppm or less, and heated at 121 ° C. for about 1 minute. Sterilized, cooled to 90 ° C. and filled into cans.
  • the manufacturing method of a concentrated reduction product opens a tomato concentrate in an opening process, and dilutes with water to a normal salt-free soluble solid content (4.5 or more). Then, tomatoside A is added and prepared, and it is manufactured through deaeration, sterilization, filling, cooling, and boxing steps.
  • Vegetable mixed juice Tomato juice obtained by diluting squeezed tomato juice or tomato concentrate to the specified salt-free soluble solid content (4.5 or more) with water, various vegetable juices and tomatoside A are added and formulated. It is manufactured through deaeration, sterilization, filling, cooling, and boxing processes.
  • Tomato sauce All raw materials shown in the table below are mixed, nitrogen gas is mixed and degassed under reduced pressure to reduce the dissolved oxygen concentration to 3 ppm or less, then filled into No. 2 can, and retort sterilized at 110 ° C. for 30 minutes do.
  • the composition comprising tomatoside A of the present invention or a physiologically acceptable salt thereof as an active ingredient is for preventing or treating dyslipidemia such as hypercholesterolemia or hypertriglyceridemia and diseases related thereto. Can be used. Moreover, it can utilize as a cholesterol rise inhibitor, a triglyceride rise inhibitor, and a liver cholesterol accumulation inhibitor.
  • the present invention is useful in the fields of pharmaceuticals, food and drinks, and the like. By adding the composition and agent to foods (especially processed tomato processed foods and drinks), it is easy to ingest without losing the flavor, and has better efficacy than ingesting tomatoside A or a physiologically acceptable salt thereof alone. Therefore, the composition and the agent can be continuously ingested without burden on the subject. Furthermore, according to the present invention, since the composition and the agent can be easily and efficiently separated from the tomato juice lees, the waste can be effectively used.

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Abstract

La présente invention a pour objet une composition destinée à la prévention ou au traitement d'une dyslipidémie et d'une maladie qui y est associée comme une hypercholestérolémie ou une hypertriglycéridémie, et un ou plusieurs membres choisis parmi un médicament destiné à la prévention d'une augmentation du taux de cholestérol, un médicament destiné à la prévention d'une augmentation du taux de triglycérides et un médicament destiné à la prévention de l'accumulation de cholestérol dans le foie. La présente invention a pour autre objet un procédé de production de cette composition ; un médicament destiné à la prévention d'une augmentation du taux de cholestérol, un médicament destiné à la prévention d'une augmentation du taux de triglycérides, un médicament destiné à la prévention de l'accumulation de cholestérol dans le foie et une composition destinée à la prévention ou au traitement d'une maladie associée à une dyslipidémie, lesdits médicaments et ladite composition contenant chacun du tomatoside A ou l'un de ses sels physiologiquement acceptables ; un procédé de production d'une composition contenant du tomatoside A ou l'un de ses sels physiologiquement acceptables, ledit procédé comprenant une étape d'extraction d'un matériau dérivé des fruits de la tomate y compris des graines de tomate avec un solvant organique en tant que solvant d'extraction, ledit solvant organique étant utilisé dans une quantité de 10 % en volume ou plus mais inférieure à 90 % en volume.
PCT/JP2012/053934 2011-02-21 2012-02-20 Composition contenant du tomatoside a Ceased WO2012115026A1 (fr)

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Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2016054720A (ja) * 2014-09-11 2016-04-21 キッコーマン株式会社 トマト含有飲食品
JP2016063795A (ja) * 2014-09-25 2016-04-28 キッコーマン株式会社 トマト飲料
JP2017192312A (ja) * 2016-04-18 2017-10-26 キッコーマン株式会社 トマトシドａを含む血糖上昇を抑制するための飲食品
JP2018523651A (ja) * 2015-07-27 2018-08-23 ミン−ダック ファーマーズ コーペレイティブＭｉｎｎ−Ｄａｋ Ｆａｒｍｅｒｓ Ｃｏｏｐｅｒａｔｉｖｅ 農産物からサポニンを抽出するためのプロセス
JP2020203856A (ja) * 2019-06-17 2020-12-24 株式会社ダイセル トマチジン含有抽出物の製造方法

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WO1995000018A1 (fr) * 1993-06-21 1995-01-05 Medical Research Foundation Of Oregon Glycosides sequestrant le cholesterole inhibant son absorption intestinale
CN101199730A (zh) * 2006-12-13 2008-06-18 李甲怀 大蒜甙与大蒜生物活性成分组合物的提取工艺及其用途

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JPH11137211A (ja) * 1997-11-13 1999-05-25 Bizen Kasei Kk 風味の改良されたギムネマシルベスタエキスおよびそ の製造法
WO2006030771A1 (fr) * 2004-09-14 2006-03-23 Hosoda Shc Inc. Extrait de gnetum
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WO1995000018A1 (fr) * 1993-06-21 1995-01-05 Medical Research Foundation Of Oregon Glycosides sequestrant le cholesterole inhibant son absorption intestinale
CN101199730A (zh) * 2006-12-13 2008-06-18 李甲怀 大蒜甙与大蒜生物活性成分组合物的提取工艺及其用途

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2016054720A (ja) * 2014-09-11 2016-04-21 キッコーマン株式会社 トマト含有飲食品
JP2016063795A (ja) * 2014-09-25 2016-04-28 キッコーマン株式会社 トマト飲料
JP2018523651A (ja) * 2015-07-27 2018-08-23 ミン−ダック ファーマーズ コーペレイティブＭｉｎｎ−Ｄａｋ Ｆａｒｍｅｒｓ Ｃｏｏｐｅｒａｔｉｖｅ 農産物からサポニンを抽出するためのプロセス
JP2017192312A (ja) * 2016-04-18 2017-10-26 キッコーマン株式会社 トマトシドａを含む血糖上昇を抑制するための飲食品
JP2020203856A (ja) * 2019-06-17 2020-12-24 株式会社ダイセル トマチジン含有抽出物の製造方法

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