WO2012115026A1 - Tomatoside a-containing composition - Google Patents
Tomatoside a-containing composition Download PDFInfo
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- 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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- tomatoside
- cholesterol
- tomato
- composition
- acceptable salt
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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)
- 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
The purpose of the present invention is to provide a composition for preventing or treating dyslipidemia and a disease related thereto such as hypercholesterolemia or hypertriglyceridemia, and one or more members selected from among a drug for preventing an increase in cholesterol level, a drug for preventing an increase in triglyceride level and a drug for preventing cholesterol accumulation in the liver. Another purpose of the present invention is to provide a method for producing the same. A drug for preventing an increase in cholesterol level, a drug for preventing an increase in triglyceride level, a drug for preventing cholesterol accumulation in the liver, and a composition for preventing or treating a disease related to dyslipidemia, said drugs and composition each containing tomatoside A or a physiologically acceptable salt thereof. A method for producing a composition containing tomatoside A or a physiologically acceptable salt thereof, said method comprising a step for extracting a material derived from tomato fruits including tomato seeds with an organic solvent as an extraction solvent, said organic solvent being used in an amount of 10 vol% or more but less than 90 vol%.
Description
本発明は、トマト種子由来サポニンであるトマトシドA又はその生理学的に許容される塩を含有する、脂質異常症に関連する疾患の予防又は治療用組成物及びその製造方法に関する。本発明はまた、トマトシドA又はその生理学的に許容される塩を含有するコレステロール上昇抑制剤、トリグリセリド上昇抑制剤及び肝中コレステロール蓄積抑制剤に関する。
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.
近年日本人の食生活の欧米化の結果として、コレステロールや脂質を過剰に摂取する人が増え、生体内のコレステロールやトリグリセリドが上昇して脂質異常症及びこれに関連した各種疾病を引き起こす原因になっている。
As a result of the westernization of Japanese dietary habits in recent years, the number of people who consume excessive amounts of cholesterol and lipids has increased, and cholesterol and triglycerides in the body have risen, causing dyslipidemia and various diseases associated therewith. ing.
平成18年国民健康調査の概要によると、このような脂質異常症が疑われる人は日本国内で少なくとも約1410万人と推計されている。脂質異常症は動脈硬化性疾患など、多様な疾患を引き起こす原因となる。例えば動脈硬化性疾患のうち、特に心筋梗塞を中心とした心血管系疾患と、脳梗塞・脳卒中を中心とした脳血管障害による死亡は、がんと並んで大きな位置を占め、日本人の死因の約30%に及んでいる。その危険性は、急速な高齢化社会への移行によってさらに高まることが予想される。日本国内のみならず世界的にも有効な予防法、治療法の確立が急務である。
According to the outline of the 2006 National Health Survey, it is estimated that there are at least about 14.1 million people in Japan who are suspected of having such dyslipidemia. Dyslipidemia causes various diseases such as arteriosclerotic diseases. For example, among 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. There is an urgent need to establish effective prevention and treatment methods not only in Japan but also worldwide.
このような状況に対して薬物療法のみならず、食事内容や運動を中心とする生活習慣の是正が推奨されており、これまでにコレステロール低下作用又はコレステロール上昇抑制作用を有する食品成分として、食物繊維、植物ステロール、サポニン、リン脂質、大豆タンパク質等が報告されている(例えば、非特許文献1参照)。
In this situation, not only pharmacotherapy, but also correction of lifestyle habits centering on meal content and exercise has been recommended, and as 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).
一方、トマトは、野菜の中で最も多く栽培されており、世界中で広く食され、人々の健康増進に高く貢献している野菜である。トマトには、例えば食物繊維(セルロース、ペクチン等)等、多くの種類の機能的な栄養成分が含まれ、長年にわたってその研究が進められてきた。
On the other hand, 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.
トマトに含まれる代表的なカロテノイド類であるリコピンは、強い抗酸化活性を有することが知られ、前立腺がん、すい臓がん、肺がんの発症リスクの低下、肝機能の正常化、心筋梗塞予防、白内障予防等の効果が報告されている。また、トマト果皮に存在するポリフェノールの一種であるナリンゲニンカルコンが花粉症などの鼻アレルギーに代表されるI型アレルギーを抑制するという報告がある(例えば、非特許文献2、3参照)。
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. In addition, there is a report that 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).
トマトに含まれる成分として、微量ではあるが未熟トマト果実中にα-トマチンと呼ばれるアルカロイド配糖体の存在が知られている。α-トマチンにはステロイド系配糖体であるトマチジンにキシロース1分子、グルコース2分子、ガラクトース1分子が結合しており、その濃度は果実の成熟とともに減少する。α-トマチンは、コレステロールと不溶性複合体を形成する特性があり、ハムスターへの給餌試験では悪玉コレステロールであるLDLコレステロール値を減少させるという報告がある(例えば、非特許文献4参照)。
As a component contained in tomato, the presence of alkaloid glycoside called α-tomatine is known in immature tomato fruit although it is a trace amount. α-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. α-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).
従来提案されているトマト由来の脂質代謝改善剤として、特許文献1は、トマト果実収穫後のトマト地上部(茎・葉など)から得られたトマチジンを有効成分として含む、動脈硬化の予防・治療剤、血中コレステロール低下剤及びマクロファージの泡沫化阻害剤を開示する。特許文献2は、リコピンを含まず、水不溶性粒子状物質を含まない、水溶性トマト抽出物又はそのフラクションの、血漿トリグリセリド濃度低下作用について開示する。
As a conventionally proposed tomato-derived lipid metabolism improving agent, 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.
また、サポニンの一種であるトマトシドAは、トマト種子(種子を含むゼリー部)に非常に多く存在する成分であり(例えば、非特許文献6参照)、界面活性作用を有することが知られている(例えば、非特許文献5参照)。しかしながら、これまでにトマト種子に含まれる成分による生理活性に関する報告はない。
In addition, 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.
本発明は、高コレステロール血症又は高トリグリセリド血症のような脂質異常症及びこれに関連する疾患を予防又は治療するための組成物を提供することを目的とする。本発明はまた、コレステロール上昇抑制剤、トリグリセリド上昇抑制剤及び肝中コレステロール蓄積抑制剤のいずれか1以上を提供することも目的とする。
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.
上記の課題を解決するために、本発明者らは鋭意研究を重ね、トマトジュース、トマトピューレ、トマトペーストなどに用いるトマト果実の搾汁液を製造する際に発生する搾汁粕から分離したトマトシドAがコレステロールやトリグリセリト等の血中脂質濃度の上昇を抑制し、肝臓中のコレステロールの蓄積を抑制する作用を有することを発見した。また、このトマトシドAを含むトマト加工飲食品は、風味が損なわれることなく、上記の作用がより強化された食品となることを見出した。また、トマトシドAを含む組成物をトマト搾汁粕から容易に効率よく分離する方法を見出した。
In order to solve the above-mentioned problems, 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 | action was strengthened, without the flavor being impaired. Moreover, the method which isolate | separates the composition containing tomatoside A easily and efficiently from a tomato juice lees was discovered.
本発明者らによる前記の知見に基づく本発明は以下の通りである:
[1]トマトシドA又はその生理学的に許容される塩を含有するコレステロール上昇抑制剤;
[2]トマトシドA又はその生理学的に許容される塩を含有するトリグリセリド上昇抑制剤;
[3]トマトシドA又はその生理学的に許容される塩を含有する肝中コレステロール蓄積抑制剤;
[4]トマトシドA又はその生理学的に許容される塩を含有する、脂質異常症に関連する疾患の予防又は治療用組成物;
[5]前記トマトシドA又はその生理学的に許容される塩の含有量が、0.001~80重量%である、[1]~[4]のいずれかに記載の剤又は組成物;
[6][1]~[4]のいずれか1項に記載の剤又は組成物を配合したトマト加工飲食品であって、前記トマトシドA又はその生理学的に許容される塩の含有量が、0.001~80重量%である、トマト加工飲食品;
[7]トマト種子を含むトマト果実由来物を、抽出溶媒として10体積%以上90体積%未満の有機溶媒を用いて抽出する工程を含む、トマトシドA又はその生理学的に許容される塩を含む組成物の製造方法;並びに
[8]前記有機溶媒が、エタノール溶媒である、[7]に記載の製造方法。 Based on the above findings by the present inventors, 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 a tomato fruit-derived product containing tomato seeds using an organic solvent of 10% by volume or more and less than 90% by volume as an extraction solvent. And [8] The production method according to [7], wherein the organic solvent is an ethanol solvent.
[1]トマトシドA又はその生理学的に許容される塩を含有するコレステロール上昇抑制剤;
[2]トマトシドA又はその生理学的に許容される塩を含有するトリグリセリド上昇抑制剤;
[3]トマトシドA又はその生理学的に許容される塩を含有する肝中コレステロール蓄積抑制剤;
[4]トマトシドA又はその生理学的に許容される塩を含有する、脂質異常症に関連する疾患の予防又は治療用組成物;
[5]前記トマトシドA又はその生理学的に許容される塩の含有量が、0.001~80重量%である、[1]~[4]のいずれかに記載の剤又は組成物;
[6][1]~[4]のいずれか1項に記載の剤又は組成物を配合したトマト加工飲食品であって、前記トマトシドA又はその生理学的に許容される塩の含有量が、0.001~80重量%である、トマト加工飲食品;
[7]トマト種子を含むトマト果実由来物を、抽出溶媒として10体積%以上90体積%未満の有機溶媒を用いて抽出する工程を含む、トマトシドA又はその生理学的に許容される塩を含む組成物の製造方法;並びに
[8]前記有機溶媒が、エタノール溶媒である、[7]に記載の製造方法。 Based on the above findings by the present inventors, 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 a tomato fruit-derived product containing tomato seeds using an organic solvent of 10% by volume or more and less than 90% by volume as an extraction solvent. And [8] The production method according to [7], wherein the organic solvent is an ethanol solvent.
さらに、本発明は、以下の方法にも関する:
[9]トマトシドA又はその生理学的に許容される塩の有効量を投与する工程を含む、コレステロール上昇抑制方法;
[10]トマトシドA又はその生理学的に許容される塩の有効量を投与する工程を含む、トリグリセリド上昇抑制方法;
[11]トマトシドA又はその生理学的に許容される塩の有効量を投与する工程を含む、肝中コレステロール蓄積抑制方法;及び
[12]トマトシドA又はその生理学的に許容される塩の有効量を投与する工程を含む、脂質異常症に関連する疾患の予防又は治療方法。 Furthermore, 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.
[9]トマトシドA又はその生理学的に許容される塩の有効量を投与する工程を含む、コレステロール上昇抑制方法;
[10]トマトシドA又はその生理学的に許容される塩の有効量を投与する工程を含む、トリグリセリド上昇抑制方法;
[11]トマトシドA又はその生理学的に許容される塩の有効量を投与する工程を含む、肝中コレステロール蓄積抑制方法;及び
[12]トマトシドA又はその生理学的に許容される塩の有効量を投与する工程を含む、脂質異常症に関連する疾患の予防又は治療方法。 Furthermore, 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.
本発明により、高コレステロール血症又は高トリグリセリド血症のような脂質異常症及びこれに関連する疾患を予防又は治療するための組成物並びにコレステロール上昇抑制剤、トリグリセリド上昇抑制剤、及び肝中コレステロール蓄積抑制剤のいずれか1以上を提供することができる。特に該組成物及び剤を、飲食品(特にトマト加工飲食品)に配合することにより、風味が損なわれず摂取しやすく、しかもトマトシドA又はその生理学的に許容される塩を単独で摂取するよりも効能のよりすぐれたな飲食品も提供することができる。さらに、本発明によれば、該組成物及び剤をトマト搾汁粕より容易に効率よく分離することができる。
According to the present invention, 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 Any one or more of the inhibitors can be provided. In particular, by blending the composition and the agent into foods and drinks (especially processed tomato foods and drinks), the flavor is not impaired and it is easy to ingest, and tomatoside A or a physiologically acceptable salt thereof is ingested alone. Foods and drinks with better efficacy can also be provided. Furthermore, according to the present invention, the composition and the agent can be easily and efficiently separated from the tomato juice lees.
以下、本発明を具体的に説明する。本発明の組成物及び剤(以下、単に「本発明の組成物」ともいう)の有効成分であるトマトシドA(トマトサイドA、tomatosideA)は、以下の構造を有する化合物である。
Hereinafter, the present invention will be specifically described. 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.
トマトシドAは、サポニンの一種であり、トマト種子に多く含まれることが知られる水に難溶性の化合物である。本発明の組成物における有効成分であるトマトシドAの生理学的に許容される塩としては上記の構造を有する化合物のナトリウム塩、カリウム塩等が挙げられるが、所望の作用を有し、生理学的に許容される塩であれば特に限定されない。以下、トマトシドA及び/又はその生理学的に許容される塩を、単に「トマトシドA」ともいう。
Tomatoside A is a kind of saponin and is a water-insoluble compound known to be contained in a large amount in tomato seeds. Examples of 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. Hereinafter, tomatoside A and / or a physiologically acceptable salt thereof is also simply referred to as “tomatoside A”.
トマトシドAとしては、化学的に合成したものを用いてもよいが、より簡便には、トマト種子を含むトマト果実由来物を、抽出溶媒として10体積%以上90体積%未満の有機溶媒を用いて抽出する工程を含む方法により、トマトシドAを含む組成物を得ることができる。以下にその方法を詳述する。
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. By the method including the step of extracting, a composition containing tomatoside A can be obtained. The method will be described in detail below.
原料となるトマト果実由来物は、トマト種子を含むものであれば特に限定されないが、トマトの品種や成熟度によって、種子の形状、数量が異なることを考慮することが好ましい。トマト果実の搾汁液を得る過程において得られる搾汁粕は、一般的に廃棄されるか、家畜飼料となるが、この搾汁粕を用いれば、廃棄原料を有効利用でき、しかも高濃度のトマトシドAを含む組成物を容易に効率よく得ることができるため好ましい。トマトジュース、トマトピューレ、トマトペーストなどに用いるトマト果実の搾汁液は、常法により、トマト果実を洗浄し、破砕したのち予備加熱を行い、次いで、これを搾汁して得られる。この搾汁の過程において、果実の約1~5%が搾汁粕として発生する。搾汁粕は主として果皮と種子から構成されており、この中には水溶性食物繊維であるペクチンや不溶性食物繊維であるセルロース、ヘミセルロースなどの繊維質が豊富に含まれるだけでなく、ポリフェノール類やサポニン類も残存している。
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.
上記のトマト果実由来物を、抽出溶媒を用いて、例えば後述の実施例に記載のように、当業者に公知の手法を用いて抽出する。抽出効率を高めるため、トマト果実由来物は乾燥品であることが好ましい。抽出溶媒としては、食品添加物の抽出溶剤となり得る有機溶媒であれば特に限定されず、例えば、アセトン、エタノール、エチルメチルケトン、グリセリン、酢酸エチル、酢酸メチル、ジエチルエーテル、シクロヘキサン、ジクロロメタン、食用油脂、1,1,1,2-テトラフルオロエタン、1,1,2-トリクロロエテン、1-ブタノール、2-ブタノール、1-プロパノール、2-プロパノール、プロピレングリコール、ヘキサン、水、メタノール等から選択される1又は複数の有機溶媒を用いることができる。これらのうち好ましくは、エタノール(10体積%以上90体積%未満)、メタノール(10体積%以上90体積%未満)、1-ブタノール(30体積%以上90体積%未満)及びヘキサン(5体積%70体積%未満)から選択される有機溶媒を用いることができ、最も好ましくはエタノールを用いることができる。例えば、抽出溶媒として、10体積%以上90体積%未満のエタノール溶媒を用いることができ、好ましくは30体積%以上70体積%以下のエタノール溶媒を用いることができ、より好ましくは70体積%程度のエタノール溶媒を用いることができる。なお、70体積%のエタノール溶媒とは、エタノールと水の体積比7:3の混合物を指す。
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. In order to increase the extraction efficiency, 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. For example, acetone, ethanol, ethyl methyl ketone, glycerin, ethyl acetate, methyl acetate, diethyl ether, cyclohexane, dichloromethane, edible oils and fats 1,1,1,2-tetrafluoroethane, 1,1,2-trichloroethene, 1-butanol, 2-butanol, 1-propanol, 2-propanol, propylene glycol, hexane, water, methanol, etc. One or more organic solvents can be used. Of these, 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. For example, 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.
抽出溶媒のpHは、トマトシドAが抽出される限り特に制限されないが、抽出効率の観点から、強酸性ではないことが望ましく、pH4以上が好ましく、pH5以上がより好ましい。
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.
抽出時の温度は、トマトシドAが抽出される限り特に制限されないが、抽出効率の観点から、0℃以上55℃未満が好ましく、5℃以上40℃以下がより好ましい。作業容易性の観点から、室温程度の25℃前後で抽出を行うことが特に好ましい。
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.
抽出時間は、トマトシドAが抽出される限り特に制限されないが、抽出効率及び作業容易性の観点から、30分以上が好ましく、1時間以上2時間以下がより好ましい。抽出は、静置抽出及び撹拌抽出のいずれの方法でも行うことができるが、抽出効率の観点から、好ましくは撹拌抽出を行う。
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.
抽出回数は、トマトシドAが抽出される限り特に制限されず、例えば1~3回程度の抽出を行うことができるが、70体積%のエタノール溶媒を抽出溶媒とし、室温で1時間抽出した場合、1~2回の抽出で十分な抽出をすることができる。
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. When 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.
抽出後、濾過により残渣を除去して得られた抽出液は、常法により、減圧下での濃縮や、凍結乾燥を行い、トマトシドAを含む組成物を得ることができる。このようにして得られた組成物は、トマトシドAの他、原料となるトマト果実由来物に含まれるポリフェノール類やトマトシドA以外のサポニン類も含有し得る。得られた組成物は必要に応じて、例えばクロマトグラフィー等によりさらに精製を行ってもよい。得られた組成物にトマトシドAが含まれているかは、例えば標準品を用いたHPLC等、常法により確認することができる。得られた組成物は、そのまま本発明の組成物としてもよいし、そのまま又は精製物を下記の医薬品及び飲食品に配合してもよい。
After the extraction, 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.
トマトシドAは、後述の実施例に記載の通り、in vitroでコレステロール吸着活性を示し、in vivoで、コレステロール負荷による血中脂質濃度の上昇抑制作用(特に、血清総コレステロール上昇抑制作用、血清非HDLコレステロール上昇抑制作用及び血清トリグリセライド上昇抑制作用)や、コレステロール負荷によって引き起こされた高コレステロール血症を改善する作用を有する。この作用は、従来コレステロール低下作用が知られる大豆サポニンと比較しても高い効果である。また、上記の作用に伴い、動脈硬化のリスクを軽減する作用も有する。さらに、コレステロール負荷による肝臓へのコレステロール蓄積を予防する作用も有する。
従って、トマトシドAを含有する組成物は、コレステロール上昇抑制剤(特に血中コレステロール上昇抑制剤)、トリグリセリド上昇抑制剤又は肝中コレステロール蓄積抑制剤として用いることができる。なお、本明細書中において、特に記載のない限り「コレステロール」とは「血中コレステロール」を意味する。また、トマトシドAを含有する組成物を、脂質異常症に関連する疾患、例えば高コレステロール血症又は高トリグリセリド血症に関連する疾患の予防又は治療用組成物や、脂質異常症に関連する状態の予防又は改善用組成物として、用いることができる。これらの剤及び組成物を、そのまま、ヒトを含む動物等に投与することができるほか、医薬品(医薬組成物)及び飲食品に配合して利用することができる。 As described in Examples below, 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 | action which reduces the risk of arteriosclerosis with said effect | action. Furthermore, it also has the effect of preventing cholesterol accumulation in the liver due to cholesterol loading.
Therefore, 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. In the present specification, unless otherwise specified, “cholesterol” means “blood cholesterol”. In addition, 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.
従って、トマトシドAを含有する組成物は、コレステロール上昇抑制剤(特に血中コレステロール上昇抑制剤)、トリグリセリド上昇抑制剤又は肝中コレステロール蓄積抑制剤として用いることができる。なお、本明細書中において、特に記載のない限り「コレステロール」とは「血中コレステロール」を意味する。また、トマトシドAを含有する組成物を、脂質異常症に関連する疾患、例えば高コレステロール血症又は高トリグリセリド血症に関連する疾患の予防又は治療用組成物や、脂質異常症に関連する状態の予防又は改善用組成物として、用いることができる。これらの剤及び組成物を、そのまま、ヒトを含む動物等に投与することができるほか、医薬品(医薬組成物)及び飲食品に配合して利用することができる。 As described in Examples below, 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 | action which reduces the risk of arteriosclerosis with said effect | action. Furthermore, it also has the effect of preventing cholesterol accumulation in the liver due to cholesterol loading.
Therefore, 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. In the present specification, unless otherwise specified, “cholesterol” means “blood cholesterol”. In addition, 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.
さらに、上記のトマトシドAの作用に基づき、トマトシドAの有効量を投与する工程を含む、コレステロール上昇抑制方法、トリグリセリド上昇抑制方法、肝中コレステロール蓄積抑制方法、及び脂質異常症に関連する疾患の予防又は治療方法を提供することもできる。
Furthermore, based on the action of tomatoside A described above, 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 Alternatively, a method of treatment can be provided.
脂質異常症に関連する疾患及び状態としては、例えば、高コレステロール血症に関連する疾患、高LDLコレステロール血症に関連する疾患、高トリグリセリド血症に関連する疾患等が挙げられる。より具体的には、動脈硬化症、動脈硬化性疾患である狭心症、心筋梗塞等の虚血性心疾患、脳梗塞、脳卒中脳血栓、脳出血、クモ膜下出血等の脳血管疾患、膵炎等が挙げられる。
Examples of 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.
上記の作用を有する本発明の組成物を、例えば高コレステロール血症、高LDLコレステロール血症、高トリグリセリド血症等の脂質異常症に対する効果が知られている他の食品や有効成分と併用して投与することにより、相加効果又は相乗効果を得ることもできる。このような食品や有効成分としては、例えば、各種食物繊維(低分子アルギン酸ナトリウム、サイリウム、ペクチン、小麦ふすま、リグニン等)、茶カテキン、キトサン、各種植物ステロール、各種サポニン(大豆サポニン、アルファルファサポニン、ユッカサポニン、薬用人参サポニン、ヒヨコマメサポニン等)、各種リン脂質、大豆タンパク質、キャベツ又はブロッコリー由来の天然アミノ酸、各種脂肪酸(13-oxo-9,11-オクタデカジエン酸等)等が挙げられる。
The 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. By administration, an additive effect or a synergistic effect can also be obtained. Examples of 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.
本発明の組成物並びにこれを配合した飲食品及び医薬品は、有効成分であるトマトシドAを、乾燥重量で好ましくは0.001~80重量%、より好ましくは0.005~60重量%、特に好ましくは0.005~0.6重量%含有する。トマトシドA含有量が少なすぎると、所望の効果を得られないことがある。また、本発明の組成物を特に飲食品に配合する場合、トマトシドA含有量の増加に伴い苦味が増す場合もあることも考慮してトマトシドAを配合することが好ましい。
The 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 | blending especially the composition of this invention with food-drinks, it is preferable to mix | blend tomatoside A also considering that a bitter taste may increase with the increase in tomatoside A content.
本発明の組成物を医薬品に配合する場合、薬学的に許容可能な賦形剤を添加して医薬製剤とすることができる。医薬製剤は、錠剤、カプセル剤、顆粒剤、細粒剤、散剤、液剤、シロップ剤、チュアブル、トローチ等の経口剤、軟膏剤、ゲル剤、クリーム剤、貼付剤等の外用剤、注射剤、舌下剤、吸入剤、点眼剤、坐剤等の剤型であることができる。好ましい剤型は、経口剤である。
When the composition of the present invention is blended with a pharmaceutical product, 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.
本発明の組成物の投与量は、対象疾患及び状態、疾患の程度、対象者の年齢、体重等に応じて適宜設定することができるが、通常成人一日当たりトマトシドAを乾燥物換算で例えば0.1~1000mg/kg体重、好ましくは例えば0.4~200mg/kg体重程度投与することができる。投与は単回投与でも数回に分けた投与でもよい。
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.
本発明の組成物の投与経路は、特に限定されないが、簡便には経口投与により投与することができる。
The administration route of the composition of the present invention is not particularly limited, but can be conveniently administered by oral administration.
摂取容易性の観点から、好ましくは本発明の組成物を飲食品に配合することができる。飲食品としては、サプリメント、特定保健用食品、栄養機能食品、健康食品、機能性食品、健康補助食品、通常の飲食品等が挙げられる。形状としては、ジュース、清涼飲料、ドリンク剤、茶等の液状、ビスケット、タブレット、顆粒粉末、粉末、カプセル等の固形、ペースト、ゼリー、スープ、調味料、ドレッシング等の半流動状が例示される。これらの飲食品は、いずれも当業者に公知の手法を用いて、トマトシドAを添加して製造することができる。
From the viewpoint of ease of ingestion, the composition of the present invention can be preferably mixed with food and drink. Examples of 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.
上記の飲食品は、血中コレステロール上昇抑制作用、血中トリグリセリド上昇抑制作用、肝中コレステロール蓄積抑制作用、脂質異常症予防作用、脂質異常症改善作用、生活習慣病予防作用、生活習慣病改善作用等の作用を有する旨の表示を付した飲食品であってもよい。
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 The food / beverage products which attached | subjected the display to the effect, such as, may be sufficient.
上記の飲食品の摂取量は、用途に応じて適宜調整することができるが、例えばトマトシドAを乾燥物換算で0.1~200mg/日、好ましくは10~150mg/日、より好ましくは20~100mg/日程度摂取することができる。摂取量が多いほど所望の効果を得やすい。摂取回数は特に制限されないが、好ましくは1日1~3回であり、必要に応じて摂取回数を増減してもよい。
The intake of the above food and drink can be adjusted as appropriate according to the use. For example, 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 greater the intake, the easier it is to get the desired effect. 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.
特に本発明の組成物をトマト加工飲食品に配合した場合、トマトシドAを添加しても、トマト感やコク味が損なわれず、トマトシドAを添加しないトマト加工飲食品と比較して風味の損なわれないトマト加工飲食品となる。また、トマトシドAを配合したトマト加工飲食品は、トマトシドAのみを投与した場合と比較して、より高い血中コレステロール上昇抑制作用を有する。これは、トマト加工飲食品にもともと含まれる多数の有効成分(例えば、リコピン、α-トマチン、エスクレオサイドA及びB、食物繊維(セルロース、ペクチン等)、各種ポリフェノール等)とトマトシドAとの相方の効果によるものと考えられる。トマト加工飲食品にもともと含まれる多数の有効成分のうち一部は、コレステロールに吸着して腸管からの再吸収を阻害することにより、血中コレステロールの上昇を抑制する作用を有すると推測される。トマトシドAをトマト加工飲食品に配合した場合、トマトシドA自体の作用とこれらの有効成分の作用によって、より高いコレステロール上昇抑制作用を示すと考えられる。
In particular, when the composition of the present invention is 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. Moreover, the tomato processed food / beverage products which mix | blended tomatoside A have a higher blood cholesterol raise inhibitory effect compared with the case where only tomatoside A is administered. This is a combination of a large number of active ingredients (for example, lycopene, α-tomatine, escleoside A and B, dietary fiber (cellulose, pectin, etc.), various polyphenols, etc.) and tomatoside A contained in processed tomatoes This is considered to be due to the effect of. Some of the many active ingredients originally contained in processed tomato foods and drinks are presumed to have an action of suppressing an increase in blood cholesterol by adsorbing to cholesterol and inhibiting reabsorption from the intestinal tract. When tomatoside A is blended in tomato processed foods and drinks, it is considered that the action of tomatoside A itself and the action of these active ingredients exhibit a higher cholesterol elevation suppressing action.
従って、本発明の組成物は、好ましくはトマト加工飲食品に配合することができる。トマト加工飲食品の例としては、トマトジュース、トマトミックスジュース、トマトケチャップ、トマトソース、チリソース、トマト果汁飲料、固形トマト、トマトピューレ、トマトペースト、トマトスープ等が挙げられる。これらのトマト加工飲食品は、通常のトマト加工飲食品の製造法(レシピなど)に従い、トマトシドAを含む本発明の組成物を添加してそれぞれ通常の製法に従って調製される。なお、一般的にトマト加工飲食品は、製造過程で種子が除去され、トマトシドAはほとんど検出されない。例えば、後述の実施例1-1に記載のHPLC法でトマトジュース中のトマトシドA含有量を測定した場合、検出限界以下であったことを本発明者らは確認している。また、さらに高感度の分析法(LC/MS)による測定も行ったところ、トマトジュース中のトマトシドA含有量は0.0005重量%以下であると考えられた。
Therefore, the composition of the present invention can be preferably blended in tomato processed foods and drinks. Examples of 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. In general, tomato processed foods and drinks have seeds removed during the production process, and tomatoside A is hardly detected. For example, 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. Moreover, when the measurement by the more sensitive analysis method (LC / MS) was also performed, the tomatoside A content in tomato juice was considered to be 0.0005% by weight or less.
以下に実施例を挙げて本発明を詳細に説明するが、本発明の技術的範囲はこれらの記載によって何ら制限されるものではない。
Hereinafter, the present invention will be described in detail with reference to examples, but the technical scope of the present invention is not limited by these descriptions.
[実施例1]
(トマト搾汁粕からのトマトシドAの抽出)
1-1.抽出溶媒の検討
完熟した加工用トマト果実をブラシ洗浄し、チョッパーで破砕した後、間接式のチューブ型加熱器にて予備加熱を行い、これをパルパーフィニッシャーにて搾汁して搾汁液を得た。搾汁過程で発生した搾汁粕を凍結乾燥し、さらに粉砕してトマト種子を含むトマト搾汁粕の乾燥物を得た。得られた乾燥物20gに、表1に示す各抽出溶媒1,000mLを加え、25℃の温度条件下にて2時間撹拌抽出した後、濾過した。得られた抽出液を減圧下にて濃縮し、トマトシドA抽出物を得た。抽出溶媒としては、10体積%エタノール(水とエタノールの体積比9:1の混合物)、30体積%エタノール(水とエタノールの体積比7:3の混合物)、50体積%エタノール(水とエタノールの体積比5:5の混合物)、70体積%エタノール(水とエタノールの体積比3:7の混合物)、90体積%エタノール(水とエタノールの体積比1:9の混合物)、0.1%酢酸添加した70体積%エタノール(水、エタノール、酢酸の体積比3:7:0.01の混合物)、1%酢酸添加した70体積%エタノール(水、エタノール、酢酸の体積比3:7:0.1の混合物)を用いたときの各抽出物のトマトシドAの相対濃度を表1中に併記した。相対濃度は以下に記載の方法で算出した。 [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. As an extraction solvent, 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.
(トマト搾汁粕からのトマトシドAの抽出)
1-1.抽出溶媒の検討
完熟した加工用トマト果実をブラシ洗浄し、チョッパーで破砕した後、間接式のチューブ型加熱器にて予備加熱を行い、これをパルパーフィニッシャーにて搾汁して搾汁液を得た。搾汁過程で発生した搾汁粕を凍結乾燥し、さらに粉砕してトマト種子を含むトマト搾汁粕の乾燥物を得た。得られた乾燥物20gに、表1に示す各抽出溶媒1,000mLを加え、25℃の温度条件下にて2時間撹拌抽出した後、濾過した。得られた抽出液を減圧下にて濃縮し、トマトシドA抽出物を得た。抽出溶媒としては、10体積%エタノール(水とエタノールの体積比9:1の混合物)、30体積%エタノール(水とエタノールの体積比7:3の混合物)、50体積%エタノール(水とエタノールの体積比5:5の混合物)、70体積%エタノール(水とエタノールの体積比3:7の混合物)、90体積%エタノール(水とエタノールの体積比1:9の混合物)、0.1%酢酸添加した70体積%エタノール(水、エタノール、酢酸の体積比3:7:0.01の混合物)、1%酢酸添加した70体積%エタノール(水、エタノール、酢酸の体積比3:7:0.1の混合物)を用いたときの各抽出物のトマトシドAの相対濃度を表1中に併記した。相対濃度は以下に記載の方法で算出した。 [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. As an extraction solvent, 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.
相対濃度の算出方法:得られた各抽出液を、常法により、減圧下で濃縮し、逆相系固層抽出カラム(Sep-Pak C18、Waters製)に吸着させた後、水洗浄し、次いでメタノールで溶出させた。得られたメタノール溶出液を再度減圧下で濃縮した試料溶液をフィルター(0.45μm)で濾過し、逆相系カラム(Capcell Pak C18、4.6mm×150mm、資生堂製)を装着した高速液体クロマトグラフ(型式SCL-10AVP、島津製作所製)を用いて、カラム温度35℃でグラディエント法により分析した。移動相A液は蒸留水、B液はアセトニトリル溶液とし、試料注入量は10μL、検出は蒸発光散乱検出器(型式ELSD-LTII、島津製作所製)により行った。測定後、最も高い抽出効率を示した70体積%エタノールによる抽出濃縮物のトマトシドA含量を100として、各抽出条件のトマトシドAの相対濃度を算出した。
Calculation method of relative concentration: Each of the obtained extracts was concentrated under reduced pressure by a conventional method, adsorbed on a reverse phase solid phase extraction column (Sep-Pak C18, manufactured by Waters), washed with water, It was then eluted with methanol. A sample solution obtained by concentrating the obtained methanol eluate again under reduced pressure was filtered through a filter (0.45 μm), and a high-performance liquid chromatograph equipped with a reverse phase column (Capcell Pak C18, 4.6 mm × 150 mm, manufactured by Shiseido). Using a graph (model SCL-10AVP, manufactured by Shimadzu Corporation), analysis was performed by a gradient method at a column temperature of 35 ° C. The mobile phase A solution was distilled water, the B solution was an acetonitrile solution, the sample injection amount was 10 μL, 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.
表1に示した結果から、トマト種子サポニントマトシドAは、30~70体積%エタノールを抽出溶媒としたときに十分な抽出効果が得られることが明らかになった。なお、抽出溶媒として用いた水とエタノールの混合液自体のpH測定は困難であったが、抽出溶媒を減圧濃縮してエタノールを除去した後の「濃縮液」のpHは:抽出物試料1~4で用いた抽出溶媒についてpH4.3;抽出物試料5で用いた抽出溶媒についてpH4.2;抽出物試料6で用いた抽出溶媒についてpH3.4;抽出物試料7で用いた抽出溶媒についてpH2.8であった。濃縮液のpHよりも抽出溶媒のpHが高くなることを考慮すれば、抽出溶媒のpHは強酸性ではないことが望ましく、pH4以上が好ましく、pH5以上がより好ましいと考えられた。また、上記「相対濃度の算出方法」におけるHPLCにおいて、予め作成した既知濃度のトマトシドA標準溶液と比較することにより、トマトシドA濃度を算出したところ、70体積%エタノールを抽出溶媒としたときに得られる抽出物(未乾燥処理)のトマトシドA濃度は、1.3重量%であった。同様の手法を用いて市販のトマトジュース中のトマトシドA含有量を測定したところ検出限界以下であったため、LC/MS法を用いて測定を行った結果、市販のトマトジュース中のトマトシドA含有量は0.0005重量%以下であると考えられた。
From the results shown in Table 1, it was revealed that tomato seed saponin tomatoside A has a sufficient extraction effect when 30 to 70% by volume ethanol is used as an extraction solvent. Although it was difficult to measure the pH of the mixture of water and ethanol used as the extraction solvent, the pH of the “concentrated liquid” after concentration of the extraction solvent under reduced pressure to remove ethanol was as follows: PH 4.3 for the extraction solvent used in 4; pH 4.2 for the extraction solvent used in Extract Sample 5; pH 3.4 for the extraction solvent used in Extract Sample 6; pH 2 for the extraction solvent used in Extract Sample 7 .8. Considering that the pH of the extraction solvent is higher than the pH of the concentrate, it is desirable that the pH of the extraction solvent is not strongly acidic, preferably pH 4 or higher, and more preferably pH 5 or higher. Further, in HPLC in the above “relative concentration calculation method”, when the tomatoside A concentration was calculated by comparing with a previously prepared tomatoside A standard solution having a known concentration, it was obtained when 70 vol% ethanol was used as the extraction solvent. The tomatoside A concentration of the resulting extract (undried treatment) was 1.3% by weight. Since the tomatoside A content in the commercially available tomato juice was measured using the same method and was below the detection limit, the measurement was performed using the LC / MS method. As a result, the tomatoside A content in the commercially available tomato juice was measured. Was considered to be 0.0005% by weight or less.
1-2.抽出温度の検討
上記1-1で得られたトマト種子を含むトマト搾汁粕の乾燥物20gに、抽出溶媒として70体積%エタノール1,000mLを加え、表2の温度条件下にて2時間撹拌抽出し、濾過した。減圧下にて濃縮し、トマトシドA粗抽出物を得た。各抽出物のトマトシドAの相対濃度を上記1-1と同様の手法で測定し、表2中に併記した。トマトシドAは、70体積%エタノールを抽出溶媒として、室温から40℃程度で最も効率のよい抽出が可能であることが明らかになった。 1-2. Examination of extraction temperature To 20 g of the dried tomato juice cake containing tomato seeds obtained in 1-1 above, 1,000 mL of 70 volume% ethanol was added as an extraction solvent and stirred for 2 hours under the temperature conditions shown in Table 2. Extracted and filtered. Concentration under reduced pressure yielded a tomatoside A crude extract. The relative concentration of tomatoside A in each extract was measured in the same manner as in 1-1 above, and is also shown in Table 2. It was revealed that tomatoside A can be extracted most efficiently from room temperature to about 40 ° C. using 70 vol% ethanol as an extraction solvent.
上記1-1で得られたトマト種子を含むトマト搾汁粕の乾燥物20gに、抽出溶媒として70体積%エタノール1,000mLを加え、表2の温度条件下にて2時間撹拌抽出し、濾過した。減圧下にて濃縮し、トマトシドA粗抽出物を得た。各抽出物のトマトシドAの相対濃度を上記1-1と同様の手法で測定し、表2中に併記した。トマトシドAは、70体積%エタノールを抽出溶媒として、室温から40℃程度で最も効率のよい抽出が可能であることが明らかになった。 1-2. Examination of extraction temperature To 20 g of the dried tomato juice cake containing tomato seeds obtained in 1-1 above, 1,000 mL of 70 volume% ethanol was added as an extraction solvent and stirred for 2 hours under the temperature conditions shown in Table 2. Extracted and filtered. Concentration under reduced pressure yielded a tomatoside A crude extract. The relative concentration of tomatoside A in each extract was measured in the same manner as in 1-1 above, and is also shown in Table 2. It was revealed that tomatoside A can be extracted most efficiently from room temperature to about 40 ° C. using 70 vol% ethanol as an extraction solvent.
1-3.抽出時間の検討
上記1-1で得られたトマト種子を含むトマト搾汁粕の乾燥物20gに、抽出溶媒として70体積%エタノール1,000mLを加え、25℃にて表3の時間条件で撹拌抽出し、濾過した。減圧下にて濃縮し、トマトシドA粗抽出物を得た。各抽出物のトマトシドAの相対濃度を表3中に併記した。トマト種子サポニントマトシドAは、70体積%エタノールを抽出溶媒として、室温条件で1時間以上撹拌抽出することで十分な抽出効果が得られることが明らかになった。 1-3. Examination of extraction time To 20 g of the dried tomato juice cake containing tomato seeds obtained in 1-1 above, 1,000 mL of 70 volume% ethanol was added as an extraction solvent, and the mixture was stirred at 25 ° C. under the conditions shown in Table 3. Extracted and filtered. Concentration under reduced pressure yielded a tomatoside A crude extract. The relative concentration of tomatoside A in each extract is also shown in Table 3. It was revealed that tomato seed saponin tomatoside A can be sufficiently extracted by stirring and extracting at room temperature for 1 hour or more using 70 vol% ethanol as an extraction solvent.
上記1-1で得られたトマト種子を含むトマト搾汁粕の乾燥物20gに、抽出溶媒として70体積%エタノール1,000mLを加え、25℃にて表3の時間条件で撹拌抽出し、濾過した。減圧下にて濃縮し、トマトシドA粗抽出物を得た。各抽出物のトマトシドAの相対濃度を表3中に併記した。トマト種子サポニントマトシドAは、70体積%エタノールを抽出溶媒として、室温条件で1時間以上撹拌抽出することで十分な抽出効果が得られることが明らかになった。 1-3. Examination of extraction time To 20 g of the dried tomato juice cake containing tomato seeds obtained in 1-1 above, 1,000 mL of 70 volume% ethanol was added as an extraction solvent, and the mixture was stirred at 25 ° C. under the conditions shown in Table 3. Extracted and filtered. Concentration under reduced pressure yielded a tomatoside A crude extract. The relative concentration of tomatoside A in each extract is also shown in Table 3. It was revealed that tomato seed saponin tomatoside A can be sufficiently extracted by stirring and extracting at room temperature for 1 hour or more using 70 vol% ethanol as an extraction solvent.
1-4.抽出回数の検討
上記1-1で得られたトマト種子を含むトマト搾汁粕の乾燥物20gに、抽出溶媒として70体積%エタノール1,000mLを加え、25℃にて2時間撹拌抽出し、濾過した。濾過後の残渣について、さらに同様の抽出処理を2回行い、得られた全3回の抽出液を各々減圧下にて濃縮し、トマトシドA粗抽出物を得た。各抽出物のトマトシドAの相対濃度を表4中に記した。トマト種子サポニントマトシドAは、70体積%エタノールを抽出溶媒として、室温条件で再抽出を含めて2回の処理で、十分な抽出効果が得られることが明らかになった。 1-4. Examination of the number of extractions To 20 g of the dried tomato juice cake containing tomato seeds obtained in 1-1 above, 1,000 mL of 70 volume% ethanol was added as an extraction solvent, and the mixture was extracted by stirring at 25 ° C. for 2 hours, filtered did. The residue after filtration was further subjected to the same extraction treatment twice, and the obtained three extracts were each concentrated under reduced pressure to obtain a tomatoside A crude extract. The relative concentration of tomatoside A in each extract is shown in Table 4. It was revealed that tomato seed saponin tomatoside A has a sufficient extraction effect in two treatments including re-extraction under room temperature conditions using 70% by volume ethanol as an extraction solvent.
上記1-1で得られたトマト種子を含むトマト搾汁粕の乾燥物20gに、抽出溶媒として70体積%エタノール1,000mLを加え、25℃にて2時間撹拌抽出し、濾過した。濾過後の残渣について、さらに同様の抽出処理を2回行い、得られた全3回の抽出液を各々減圧下にて濃縮し、トマトシドA粗抽出物を得た。各抽出物のトマトシドAの相対濃度を表4中に記した。トマト種子サポニントマトシドAは、70体積%エタノールを抽出溶媒として、室温条件で再抽出を含めて2回の処理で、十分な抽出効果が得られることが明らかになった。 1-4. Examination of the number of extractions To 20 g of the dried tomato juice cake containing tomato seeds obtained in 1-1 above, 1,000 mL of 70 volume% ethanol was added as an extraction solvent, and the mixture was extracted by stirring at 25 ° C. for 2 hours, filtered did. The residue after filtration was further subjected to the same extraction treatment twice, and the obtained three extracts were each concentrated under reduced pressure to obtain a tomatoside A crude extract. The relative concentration of tomatoside A in each extract is shown in Table 4. It was revealed that tomato seed saponin tomatoside A has a sufficient extraction effect in two treatments including re-extraction under room temperature conditions using 70% by volume ethanol as an extraction solvent.
1-5トマトシドA含有調製物の製造
上記1-1~1-4の結果に基づいて最適化した抽出条件で、トマト種子を含むトマト搾汁粕の乾燥物からトマトシドA含有調製物を製造した。上記1-1で得られたトマト種子を含むトマト搾汁粕の乾燥物20gに、抽出溶媒として70体積%エタノール1000mLを加え、室温下にて2時間撹拌抽出した後、濾過した。濾過後の残渣について、さらに同様の抽出処理を1回行い、得られた全2回の抽出液を合わせて減圧下にて濃縮し、トマトシドA粗抽出物を得た。得られた粗抽出物を逆相系カラムクロマトグラフィー(YMC-ODS-A、YMC製)に吸着させ、水、40体積%メタノール、70体積%メタノール、100体積%メタノールで順次溶出して得た溶出画分を凍結乾燥して、トマトシドAを60重量%含有するトマトシドA含有調製物を得た。 1-5 Production of tomatoside A-containing preparation 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. . To 20 g of the dried tomato juice containing tomato seeds obtained in 1-1 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.
上記1-1~1-4の結果に基づいて最適化した抽出条件で、トマト種子を含むトマト搾汁粕の乾燥物からトマトシドA含有調製物を製造した。上記1-1で得られたトマト種子を含むトマト搾汁粕の乾燥物20gに、抽出溶媒として70体積%エタノール1000mLを加え、室温下にて2時間撹拌抽出した後、濾過した。濾過後の残渣について、さらに同様の抽出処理を1回行い、得られた全2回の抽出液を合わせて減圧下にて濃縮し、トマトシドA粗抽出物を得た。得られた粗抽出物を逆相系カラムクロマトグラフィー(YMC-ODS-A、YMC製)に吸着させ、水、40体積%メタノール、70体積%メタノール、100体積%メタノールで順次溶出して得た溶出画分を凍結乾燥して、トマトシドAを60重量%含有するトマトシドA含有調製物を得た。 1-5 Production of tomatoside A-containing preparation 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. . To 20 g of the dried tomato juice containing tomato seeds obtained in 1-1 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.
[実施例2]
(トマトシドA含有トマトジュースの官能評価)
実施例1-5で得られたトマトシドAを60重量%含有する調製物を、表5に示す量(トマトシドA添加量に換算して0mg~20mg/100g)添加したトマトジュース(食塩無添加)を作成し、トマト感、コク味及び苦味に関してパネリスト8名による官能評価を行った。トマトシドAを添加しないトマトジュース(対照)のトマト感、コク及び苦味の強さを7段階中4としたときの、各トマトジュースのトマト感、コク及び苦味の強さを7段階で評価し、パネリスト8名の評価の平均を算出した。結果を表5に示す。トマトシドAを添加しても、トマトジュースのトマト感やコク味は損なわれず、トマトシドAを添加しないトマトジュースと比較して遜色ないトマト加工飲食品となった。 [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.
(トマトシドA含有トマトジュースの官能評価)
実施例1-5で得られたトマトシドAを60重量%含有する調製物を、表5に示す量(トマトシドA添加量に換算して0mg~20mg/100g)添加したトマトジュース(食塩無添加)を作成し、トマト感、コク味及び苦味に関してパネリスト8名による官能評価を行った。トマトシドAを添加しないトマトジュース(対照)のトマト感、コク及び苦味の強さを7段階中4としたときの、各トマトジュースのトマト感、コク及び苦味の強さを7段階で評価し、パネリスト8名の評価の平均を算出した。結果を表5に示す。トマトシドAを添加しても、トマトジュースのトマト感やコク味は損なわれず、トマトシドAを添加しないトマトジュースと比較して遜色ないトマト加工飲食品となった。 [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.
[実施例3]
(トマトシドA含有組成物のコレステロール吸着能)
in vitroの系でトマトシドAのコレステロール吸着能を測定した。実施例1-5で得られたトマトシドAを60重量%含有する調製物を表6に示す用量でpH7.5のリン酸緩衝液1mLに分散させ、これに0.5重量%コレステロール(特級コレステロール、和光純薬工業製)のエタノール溶液0.01mLを添加し、良く撹拌した後、37℃で2時間加温した。これを10,000回転、15分間遠心分離し、上清液のコレステロール含量を測定してトマトシドA調製物のコレステロール吸着能を求めた。対照として、pH7.5リン酸緩衝液、及び表6に示す用量の大豆サポニン(一級サポニン、大豆製、和光純薬工業製)を用いた。結果を表6に併記した。トマトシドA調製物は、従来コレステロール低下作用が知られている大豆サポニンと同様に、用量に依存したコレステロール吸着活性を示した。また、トマトシドA精製物を用いて同様にコレステロール吸着能を測定したところ、上記の調製物と同様、コレステロール吸着活性を示した。 [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. , 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. This was centrifuged at 10,000 rpm for 15 minutes, and the cholesterol content of the supernatant was measured to determine the cholesterol adsorption capacity of the tomatoside A preparation. As controls, a pH 7.5 phosphate buffer and soybean saponins (primary saponins, manufactured by soybeans, manufactured by Wako Pure Chemical Industries, Ltd.) at doses shown in Table 6 were used. The results are also shown in Table 6. 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.
(トマトシドA含有組成物のコレステロール吸着能)
in vitroの系でトマトシドAのコレステロール吸着能を測定した。実施例1-5で得られたトマトシドAを60重量%含有する調製物を表6に示す用量でpH7.5のリン酸緩衝液1mLに分散させ、これに0.5重量%コレステロール(特級コレステロール、和光純薬工業製)のエタノール溶液0.01mLを添加し、良く撹拌した後、37℃で2時間加温した。これを10,000回転、15分間遠心分離し、上清液のコレステロール含量を測定してトマトシドA調製物のコレステロール吸着能を求めた。対照として、pH7.5リン酸緩衝液、及び表6に示す用量の大豆サポニン(一級サポニン、大豆製、和光純薬工業製)を用いた。結果を表6に併記した。トマトシドA調製物は、従来コレステロール低下作用が知られている大豆サポニンと同様に、用量に依存したコレステロール吸着活性を示した。また、トマトシドA精製物を用いて同様にコレステロール吸着能を測定したところ、上記の調製物と同様、コレステロール吸着活性を示した。 [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. , 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. This was centrifuged at 10,000 rpm for 15 minutes, and the cholesterol content of the supernatant was measured to determine the cholesterol adsorption capacity of the tomatoside A preparation. As controls, a pH 7.5 phosphate buffer and soybean saponins (primary saponins, manufactured by soybeans, manufactured by Wako Pure Chemical Industries, Ltd.) at doses shown in Table 6 were used. The results are also shown in Table 6. 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.
[実施例4]
(マウスへのトマトシドA含有組成物の長期投与1)
MF粉末飼料(オリエンタル酵母工業社製)にコレステロール(特級コレステロール、和光純薬工業製)とコール酸ナトリウム(コール酸ナトリウム、和光純薬工業製)を添加した試験飼料を以下の表7に記載の配合で作製し、さらに実施例1-5で得られたトマトシドAを60重量%含む調製物を添加した混餌食(トマトシドAに換算して0.33~1.0重量%配合)をマウスに投与したときの血中脂質濃度に対する効果を確認した。対象として、大豆サポニンを添加した混餌食をマウスに投与した。 [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. As a subject, a mixed diet supplemented with soy saponin was administered to mice.
(マウスへのトマトシドA含有組成物の長期投与1)
MF粉末飼料(オリエンタル酵母工業社製)にコレステロール(特級コレステロール、和光純薬工業製)とコール酸ナトリウム(コール酸ナトリウム、和光純薬工業製)を添加した試験飼料を以下の表7に記載の配合で作製し、さらに実施例1-5で得られたトマトシドAを60重量%含む調製物を添加した混餌食(トマトシドAに換算して0.33~1.0重量%配合)をマウスに投与したときの血中脂質濃度に対する効果を確認した。対象として、大豆サポニンを添加した混餌食をマウスに投与した。 [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. As a subject, a mixed diet supplemented with soy saponin was administered to mice.
5週齢の雄性C57BL6/Jマウス(日本クレア社生産)24匹を、MF粉末飼料で1週間予備飼育した後、各群6匹の対照群1、投与群2~4の4群に分けた。対照群1、及び投与群2~4をそれぞれ表7に示した試験飼料で3週間飼育した。飼料は自由摂取により投与した。
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.
試験飼料の投与開始前(0日後)並びに開始後3、7、10、14及び21日後に採血を行い、血清の総コレステロールを測定した。また、投与開始21日後に血清HDLコレステロールと血清中性脂質を測定した。測定は、コレステロールEテストワコー、HDLコレステロールテストワコー、トリグリセライドテストワコー(和光純薬社製)をそれぞれの使用説明書に従って使用して行った。非HDLコレステロール値は、総コレステロール-HDLコレステロールの値を算出して求めた。動脈硬化指数は、(総コレステロール-HDLコレステロール)/HDLコレステロールの値を算出して求めた。血清総コレステロールの測定結果を表8に、非HDLコレステロールの測定結果を表9に、血清トリグリセライドの測定結果を表10に、動脈硬化指数の測定結果を表11に、それぞれ示す。
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. In addition, 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, and Table 11 shows the measurement results of arteriosclerosis index.
表8に示すように、トマトシドAを60重量%含む調製物を混餌した試験群3及び試験群4の血清総コレステロールは、対照群1及び大豆サポニンを混餌した試験群2に比べて低い値を示した。
表9に示すように、非HDLコレステロール値についても試験群3及び試験群4が対照群1及び試験群2に比べて低い値を示した。なお、表9の結果から、大豆サポニンの投与(試験群2)は非HDLコレステロール量に影響を及ぼさなかったと考えられた。
表10に示すように、血清中性脂質についても試験群3及び試験群4が対照群1及び試験群2に比べて低い値を示した。
さらに表11に示すように、動脈硬化指数についても、試験群3及び試験群4が、対照群1と比べて有意に低い値を示し、試験群2と比べても低い値を示した。 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.
表9に示すように、非HDLコレステロール値についても試験群3及び試験群4が対照群1及び試験群2に比べて低い値を示した。なお、表9の結果から、大豆サポニンの投与(試験群2)は非HDLコレステロール量に影響を及ぼさなかったと考えられた。
表10に示すように、血清中性脂質についても試験群3及び試験群4が対照群1及び試験群2に比べて低い値を示した。
さらに表11に示すように、動脈硬化指数についても、試験群3及び試験群4が、対照群1と比べて有意に低い値を示し、試験群2と比べても低い値を示した。 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.
これらの結果から、トマトシドAは、コレステロール負荷による血中脂質濃度の上昇を抑制する作用を有し、さらにこの作用に伴い、動脈硬化指数低下作用(動脈硬化のリスクを軽減する作用)も有することが明らかとなった。また、その作用は、従来コレステロール低下作用が知られる大豆サポニンと比較して非常に高いことが明らかになった。
From these results, 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 | action is very high compared with the soybean saponin conventionally known for the cholesterol lowering effect.
[実施例5]
(トマトシドA及び/又はトマトジュース組成物のコレステロール吸着能)
in vitroの系でトマトシドAとトマトジュースの組成物によるコレステロール吸着能を測定した。実施例1-5で得られたトマトシドAを60重量%含有する調製物、及び市販の食塩無添加トマトジュースを凍結乾燥して得たトマトジュース乾燥粉末を、それぞれ表12に示す用量でpH7.5のリン酸緩衝液1mLに分散させ、これに0.5重量%コレステロール(特級コレステロール、和光純薬工業製)のエタノール溶液0.01mLを添加し、良く撹拌した後、37℃で2時間加温した。これを10,000回転、15分間遠心分離し、上清液のコレステロール含量を測定してトマトシドA調製物のコレステロール吸着能を求めた。
対照としてpH7.5リン酸緩衝液を用いた。結果を表12に併記した。
トマトシドA調製物とトマトジュース乾燥粉末を混合した場合に、トマトシドA調製物単独の場合と比較してコレステロール吸着活性が向上した。トマトジュース乾燥粉末に含まれる、食物繊維(セルロース、ペクチン)や、トマトシドAとは異なるサポニンが、トマトシドAと同時にコレステロールを吸着したと考えられた。 [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. Disperse in 1 mL of 5 phosphate buffer, add 0.01 mL of ethanol solution of 0.5 wt% cholesterol (special grade cholesterol, Wako Pure Chemical Industries), stir well, and add 2 hours at 37 ° C. Warm up. This was centrifuged at 10,000 rpm for 15 minutes, and the cholesterol content of the supernatant was measured to determine the cholesterol adsorption capacity of the tomatoside A preparation.
A pH 7.5 phosphate buffer was used as a control. The results are also shown in Table 12.
When the tomatoside A preparation and the dried tomato juice powder were mixed, the cholesterol adsorption activity was improved as compared to the case of the tomatoside A preparation alone. It was considered that dietary fibers (cellulose, pectin) and saponins different from tomatoside A contained in the dried tomato juice powder adsorbed cholesterol simultaneously with tomatoside A.
(トマトシドA及び/又はトマトジュース組成物のコレステロール吸着能)
in vitroの系でトマトシドAとトマトジュースの組成物によるコレステロール吸着能を測定した。実施例1-5で得られたトマトシドAを60重量%含有する調製物、及び市販の食塩無添加トマトジュースを凍結乾燥して得たトマトジュース乾燥粉末を、それぞれ表12に示す用量でpH7.5のリン酸緩衝液1mLに分散させ、これに0.5重量%コレステロール(特級コレステロール、和光純薬工業製)のエタノール溶液0.01mLを添加し、良く撹拌した後、37℃で2時間加温した。これを10,000回転、15分間遠心分離し、上清液のコレステロール含量を測定してトマトシドA調製物のコレステロール吸着能を求めた。
対照としてpH7.5リン酸緩衝液を用いた。結果を表12に併記した。
トマトシドA調製物とトマトジュース乾燥粉末を混合した場合に、トマトシドA調製物単独の場合と比較してコレステロール吸着活性が向上した。トマトジュース乾燥粉末に含まれる、食物繊維(セルロース、ペクチン)や、トマトシドAとは異なるサポニンが、トマトシドAと同時にコレステロールを吸着したと考えられた。 [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. Disperse in 1 mL of 5 phosphate buffer, add 0.01 mL of ethanol solution of 0.5 wt% cholesterol (special grade cholesterol, Wako Pure Chemical Industries), stir well, and add 2 hours at 37 ° C. Warm up. This was centrifuged at 10,000 rpm for 15 minutes, and the cholesterol content of the supernatant was measured to determine the cholesterol adsorption capacity of the tomatoside A preparation.
A pH 7.5 phosphate buffer was used as a control. The results are also shown in Table 12.
When the tomatoside A preparation and the dried tomato juice powder were mixed, the cholesterol adsorption activity was improved as compared to the case of the tomatoside A preparation alone. It was considered that dietary fibers (cellulose, pectin) and saponins different from tomatoside A contained in the dried tomato juice powder adsorbed cholesterol simultaneously with tomatoside A.
[実施例6]
(トマトシドA及び/又はトマトジュース組成物のマウスへの長期投与)
MF粉末飼料(オリエンタル酵母工業社製)にコレステロール(特級コレステロール、和光純薬工業製)とコール酸ナトリウム(コール酸ナトリウム、和光純薬工業製)を添加した試験飼料を以下の表13に示す通り作製し、さらに実施例1-5で得られたトマトシドAを60重量%含む調製物、及び市販の食塩無添加トマトジュースを凍結乾燥して得たトマトジュース乾燥粉末を、それぞれ表13に示す用量で添加した混餌食をマウスに投与したときの血中脂質に対する効果を確認した。 [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.
(トマトシドA及び/又はトマトジュース組成物のマウスへの長期投与)
MF粉末飼料(オリエンタル酵母工業社製)にコレステロール(特級コレステロール、和光純薬工業製)とコール酸ナトリウム(コール酸ナトリウム、和光純薬工業製)を添加した試験飼料を以下の表13に示す通り作製し、さらに実施例1-5で得られたトマトシドAを60重量%含む調製物、及び市販の食塩無添加トマトジュースを凍結乾燥して得たトマトジュース乾燥粉末を、それぞれ表13に示す用量で添加した混餌食をマウスに投与したときの血中脂質に対する効果を確認した。 [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.
5週齢の雄性C57BL6/Jマウス(日本クレア社生産)24匹を、MF粉末飼料で1週間予備飼育した後、各群5匹の対照群5及び試験群6~8の4群に分けた。対照群5及び試験群6~8をそれぞれ表13に示した試験飼料で2週間飼育した。飼料は自由摂取により投与した。試験飼料の投与開始前(0日後)及び開始後3、9及び14日後に採血を行い、血清の総コレステロールを測定した。測定はコレステロールEテストワコー(和光純薬社製)を用いて行った。
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.).
血清総コレステロールの測定結果を表14に示す。トマトシドAを60重量%含む調製物を0.034重量%(トマトシドAに換算して0.02重量%)混餌した試験群6、及びトマトジュース乾燥粉末を5重量%混餌した試験群7の血清総コレステロールは、対照群5に比べて低い値を示した。また、トマトシドAを60重量%含む調製物を0.034重量%(トマトシドAに換算して0.02重量%)とトマトジュース凍結粉末5重量%を同時に混餌した試験群8の血清総コレステロールは、投与開始9及び14日後のいずれにおいても、対照群5、試験群6及び7に比べて低い値を示した。トマトシドA調製物及びトマトジュース凍結粉末は、コレステロール負荷による血中脂質濃度の上昇を抑制する作用を有し、トマトシドA調製物とトマトジュース凍結粉末を混合して投与することにより、トマトシドA調製物単独及びトマトジュース乾燥粉末単独の場合と比べて強力な作用を示すことが明らかとなった。
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 | action compared with the case of independent and tomato juice dry powder alone.
[実施例7]
(マウスへのトマトシドA含有組成物の長期投与2)
MF粉末飼料(オリエンタル酵母工業社製)にコレステロール(特級コレステロール、和光純薬工業製)とコール酸ナトリウム(コール酸ナトリウム、和光純薬工業製)を添加した試験飼料を以下の表15に記載の配合で作製してマウスに投与して、高コレステロール血症マウスとし、続いて実施例1-5で得られたトマトシドAを60重量%含む調製物を試験飼料に添加した混餌食(トマトシドAに換算して0.1重量%配合)をマウスに投与したときの血中脂質濃度に対する効果を確認した。 [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.). Prepared in combination and administered to mice to give hypercholesterolemic mice, followed by a mixed diet (tomatoside A) containing a preparation containing 60% by weight of tomatoside A obtained in Example 1-5 added to the test feed The effect on blood lipid concentration when 0.1% by weight (converted) was administered to mice was confirmed.
(マウスへのトマトシドA含有組成物の長期投与2)
MF粉末飼料(オリエンタル酵母工業社製)にコレステロール(特級コレステロール、和光純薬工業製)とコール酸ナトリウム(コール酸ナトリウム、和光純薬工業製)を添加した試験飼料を以下の表15に記載の配合で作製してマウスに投与して、高コレステロール血症マウスとし、続いて実施例1-5で得られたトマトシドAを60重量%含む調製物を試験飼料に添加した混餌食(トマトシドAに換算して0.1重量%配合)をマウスに投与したときの血中脂質濃度に対する効果を確認した。 [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.). Prepared in combination and administered to mice to give hypercholesterolemic mice, followed by a mixed diet (tomatoside A) containing a preparation containing 60% by weight of tomatoside A obtained in Example 1-5 added to the test feed The effect on blood lipid concentration when 0.1% by weight (converted) was administered to mice was confirmed.
6週齢の雄性C57BL6/Jマウス(日本クレア社生産)15匹を、MF粉末飼料で3日間予備飼育した後、表15に示した高コレステロール試験飼料で1週間飼育して、高コレステロール血症モデルマウスを作製した。このマウスを一群当たりの平均血清コレステロールが均一になるように1群5匹の対照群9、対照群10及び試験群11に分け、各群についてそれぞれ表16に示した試験飼料で3週間飼育した。飼料は自由摂取により投与した。
15 6-week-old male C57BL6 / J mice (manufactured by CLEA Japan, Inc.) were preliminarily raised for 3 days with MF powdered diet and then raised for 1 week with the high cholesterol test diet shown in Table 15 for hypercholesterolemia. A model mouse was prepared. The mice were divided into five control groups 9, control group 10 and test group 11 so that the average serum cholesterol per group was uniform, and each group was raised for 3 weeks on the test feed shown in Table 16, respectively. . The feed was administered by free consumption.
試験飼料の投与開始前(0日後)並びに開始後7、14及び21日後に採血を行い、血清の総コレステロールを測定した。また、投与開始0及び21日後に血清HDLコレステロールを測定した。投与開始21日後に各マウスの肝臓を摘出して、肝臓中の総脂質をFolch法により抽出し、総コレステロールを測定した。測定は、コレステロールEテストワコー、HDLコレステロールテストワコー及びトリグリセライドEテストワコー(和光純薬社製)をそれぞれの使用説明書に従って使用して行った。非HDLコレステロール値は、総コレステロール-HDLコレステロールの値を算出して求めた。動脈硬化指数は、(総コレステロール-HDLコレステロール)/HDLコレステロールの値を算出して求めた。血清総コレステロールの測定結果を表17に、非HDLコレステロールの測定結果を表18に、動脈硬化指数の測定結果を表19に、肝臓総コレステロールの測定結果を表20に、それぞれ示す。
Blood was collected before administration of the test feed (after 0 days) and after 7, 14 and 21 days from the start, and the total cholesterol in the serum was measured. 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.
表17に示すように、トマトシドAを60重量%含む調製物を混餌した試験群11の血清総コレステロールは、投与開始前の値より低下し、投与開始21日後には有意に低い値を示した。また、高コレステロール飼料から通常飼料に移行させた対照群10の血清コレステロールと同等の値となった。表18に示すように、投与開始21日後の非HDLコレステロール値は、対照群10及び試験群11が、対照群9に比べて有意に低い値を示した。また、総コレステロールに占めるHDLコレステロール比は、対照群10及び試験群11が、対照群9に比べて高い値を示した。さらに表19に示すように、動脈硬化指数も、対照群10及び試験群11が、対照群9と比べて有意に低い値であった。
As shown in Table 17, 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. As shown in Table 18, 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. Moreover, 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. Further, as shown in Table 19, the arteriosclerosis index was also significantly lower in the control group 10 and the test group 11 than in the control group 9.
これらの結果から、トマトシドAは、コレステロール負荷によって引き起こされた高コレステロール血症を改善し、動脈硬化のリスクを軽減する作用を有することが明らかとなった。
From these results, it was revealed that tomatoside A has an action of improving hypercholesterolemia caused by cholesterol load and reducing the risk of arteriosclerosis.
表20に示すように、トマトシドAを60重量%含む調製物を混餌した試験群11の肝中コレステロール蓄積量は、対照群9と比較して有意に低い値を示した。この結果から、トマトシドAは、コレステロール負荷による肝臓へのコレステロールの蓄積を予防する作用を有することが明らかとなった。
As shown in Table 20, the amount of cholesterol accumulated in the liver of the test group 11 fed with the preparation containing 60% by weight of tomatoside A was significantly lower than that of the control group 9. From this result, it was revealed that tomatoside A has an action of preventing cholesterol accumulation in the liver due to cholesterol load.
[実施例8]
(トマトシドAを含有するトマト加工飲食品の製造)
以下にトマトシドAを原料の一部として使用するトマト加工飲食品の製造例を示す。 [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.
(トマトシドAを含有するトマト加工飲食品の製造)
以下にトマトシドAを原料の一部として使用するトマト加工飲食品の製造例を示す。 [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.
製造例1.トマトジュース
シーズンパックトマトジュースの製造方法には、トマト洗浄、選別、破砕、加熱、搾汁、調合、脱気、殺菌、充填、冷却及び箱詰め工程があり、この調合工程で、搾汁したトマトジュースにトマトシドAを添加して調合し、有塩の場合のみ食塩が加えられ、窒素ガスを混合して減圧脱気して、溶存酸素濃度を3ppm以下とした後、121℃、約1分の加熱殺菌をして、90℃まで冷却され、缶に充填される。また、濃縮還元品の製造法は、開けだし工程で、トマト濃縮物を開けだし、規定の無塩可溶性固形分(4.5以上)に水希釈する。その後、トマトシドAを添加して調合し、脱気、殺菌、充填、冷却及び箱詰め工程を経て製造される。 Production Example 1 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. Moreover, 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.
シーズンパックトマトジュースの製造方法には、トマト洗浄、選別、破砕、加熱、搾汁、調合、脱気、殺菌、充填、冷却及び箱詰め工程があり、この調合工程で、搾汁したトマトジュースにトマトシドAを添加して調合し、有塩の場合のみ食塩が加えられ、窒素ガスを混合して減圧脱気して、溶存酸素濃度を3ppm以下とした後、121℃、約1分の加熱殺菌をして、90℃まで冷却され、缶に充填される。また、濃縮還元品の製造法は、開けだし工程で、トマト濃縮物を開けだし、規定の無塩可溶性固形分(4.5以上)に水希釈する。その後、トマトシドAを添加して調合し、脱気、殺菌、充填、冷却及び箱詰め工程を経て製造される。 Production Example 1 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. Moreover, 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.
2.野菜ミックスジュース
搾汁したトマトジュース、あるいは、トマト濃縮物を規定の無塩可溶性固形分(4.5以上)に水希釈して得たトマトジュースに、各種野菜汁及びトマトシドAを添加して調合し、脱気、殺菌、充填、冷却及び箱詰め工程を経て製造される。 2. 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.
搾汁したトマトジュース、あるいは、トマト濃縮物を規定の無塩可溶性固形分(4.5以上)に水希釈して得たトマトジュースに、各種野菜汁及びトマトシドAを添加して調合し、脱気、殺菌、充填、冷却及び箱詰め工程を経て製造される。 2. 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.
3.トマトソース
以下の表に示す全原材料を混合して、窒素ガスを混合して減圧脱気して溶存酸素濃度を3ppm以下とした後、2号缶に充填し、110℃、30分のレトルト殺菌をする。 3. 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.
以下の表に示す全原材料を混合して、窒素ガスを混合して減圧脱気して溶存酸素濃度を3ppm以下とした後、2号缶に充填し、110℃、30分のレトルト殺菌をする。 3. 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.
本発明のトマトシドA又はその生理学的に許容される塩を有効成分とする組成物は、高コレステロール血症又は高トリグリセリド血症のような脂質異常症及びこれに関連する疾患を予防又は治療するために利用することができる。また、コレステロール上昇抑制剤、トリグリセリド上昇抑制剤及び肝中コレステロール蓄積抑制剤として利用することができる。本発明は、医薬品、飲食品等の分野で有用である。該組成物及び剤を食品(特にトマト加工飲食品)に添加することにより、風味が損なわれず摂取しやすく、トマトシドA又はその生理学的に許容される塩を単独で摂取するよりも効能のよりすぐれた飲食品となり得るため、対象者への負担なく該組成物及び剤を継続摂取することが可能となる。さらに、本発明によれば、該組成物及び剤をトマト搾汁粕より容易に効率よく分離することができるため、廃棄物の有効利用が可能である。
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.
本出願は、2011年2月21日に出願された日本国特許出願第2011-34750号に基づく優先権を主張するものであり、この内容はここに参照として組み込まれる。
This application claims priority based on Japanese Patent Application No. 2011-34750 filed on February 21, 2011, the contents of which are incorporated herein by reference.
Claims (8)
- トマトシドA又はその生理学的に許容される塩を含有するコレステロール上昇抑制剤。 Cholesterol elevation inhibitor containing tomatoside A or a physiologically acceptable salt thereof.
- トマトシドA又はその生理学的に許容される塩を含有するトリグリセリド上昇抑制剤。 Triglyceride elevation inhibitor containing tomatoside A or a physiologically acceptable salt thereof.
- トマトシドA又はその生理学的に許容される塩を含有する肝中コレステロール蓄積抑制剤。 An inhibitor of hepatic cholesterol accumulation containing tomatoside A or a physiologically acceptable salt thereof.
- トマトシドA又はその生理学的に許容される塩を含有する、脂質異常症に関連する疾患の予防又は治療用組成物。 A composition for preventing or treating a disease associated with dyslipidemia, comprising tomatoside A or a physiologically acceptable salt thereof.
- 前記トマトシドA又はその生理学的に許容される塩の含有量が、0.001~80重量%である、請求項1~4のいずれか1項に記載の剤又は組成物。 The agent or composition according to any one of claims 1 to 4, wherein the content of the tomatoside A or a physiologically acceptable salt thereof is 0.001 to 80% by weight.
- 請求項1~4のいずれか1項に記載の剤又は組成物を配合したトマト加工飲食品であって、前記トマトシドA又はその生理学的に許容される塩の含有量が、0.001~80重量%である、トマト加工飲食品。 A processed tomato food or drink comprising the agent or composition according to any one of claims 1 to 4, wherein the tomatoside A or a physiologically acceptable salt thereof has a content of 0.001 to 80. Tomato processed foods and beverages that are weight%.
- トマト種子を含むトマト果実由来物を、抽出溶媒として10体積%以上90体積%未満の有機溶媒を用いて抽出する工程を含む、トマトシドA又はその生理学的に許容される塩を含む組成物の製造方法。 Production of a composition containing tomatoside A or a physiologically acceptable salt thereof, comprising a step of extracting a tomato fruit-derived product containing tomato seeds using an organic solvent of 10% by volume or more and less than 90% by volume as an extraction solvent. Method.
- 前記有機溶媒が、エタノール溶媒である、請求項7に記載の製造方法。 The production method according to claim 7, wherein the organic solvent is an ethanol solvent.
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JP2013501017A JP6042800B2 (en) | 2011-02-21 | 2012-02-20 | Tomatoside A extraction method |
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Cited By (5)
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JP2016054720A (en) * | 2014-09-11 | 2016-04-21 | キッコーマン株式会社 | Tomato-containing food and beverage |
JP2016063795A (en) * | 2014-09-25 | 2016-04-28 | キッコーマン株式会社 | Tomato beverage |
JP2017192312A (en) * | 2016-04-18 | 2017-10-26 | キッコーマン株式会社 | Food and drink comprising tomatoside a and used for inhibiting increased blood glucose |
JP2018523651A (en) * | 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 | Process for extracting saponin from agricultural products |
JP2020203856A (en) * | 2019-06-17 | 2020-12-24 | 株式会社ダイセル | Method for producing tomatidine-containing extract |
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CN1819777B (en) * | 2004-09-14 | 2012-01-04 | 株式会社细田Shc | Gnetum extract |
JP2007238509A (en) * | 2006-03-09 | 2007-09-20 | Asahi Breweries Ltd | Agent for ameliorating skin symptom, supplement, food, beverage and pharmaceutical for ameliorating skin symptom containing the same |
JP5363986B2 (en) * | 2006-10-24 | 2013-12-11 | エスケー ケミカルズ カンパニー リミテッド | Oleanane triterpene saponin compounds effective in treating dementia and mild cognitive impairment and improving cognitive function |
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- 2012-02-20 WO PCT/JP2012/053934 patent/WO2012115026A1/en active Application Filing
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WO1995000018A1 (en) * | 1993-06-21 | 1995-01-05 | Medical Research Foundation Of Oregon | Cholesterol sequestrant glycosides that inhibit intestinal cholesterol absorption |
CN101199730A (en) * | 2006-12-13 | 2008-06-18 | 李甲怀 | Extracting technique of garlic glucoside and garlic biological activity component compound and function |
Cited By (5)
Publication number | Priority date | Publication date | Assignee | Title |
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JP2016054720A (en) * | 2014-09-11 | 2016-04-21 | キッコーマン株式会社 | Tomato-containing food and beverage |
JP2016063795A (en) * | 2014-09-25 | 2016-04-28 | キッコーマン株式会社 | Tomato beverage |
JP2018523651A (en) * | 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 | Process for extracting saponin from agricultural products |
JP2017192312A (en) * | 2016-04-18 | 2017-10-26 | キッコーマン株式会社 | Food and drink comprising tomatoside a and used for inhibiting increased blood glucose |
JP2020203856A (en) * | 2019-06-17 | 2020-12-24 | 株式会社ダイセル | Method for producing tomatidine-containing extract |
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JP6042800B2 (en) | 2016-12-14 |
JPWO2012115026A1 (en) | 2014-07-07 |
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