JP2016047859A - Basal metabolism enhancer - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a safe basal metabolism enhancer without side effects which can act on autonomic nerves to regulate their functions.SOLUTION: The invention provides a basal metabolism enhancer containing tiliroside as an active ingredient. The tiliroside is contained in the extract of Rose hip, the false fruit of Rosa laevigata, the false fruit or flower of Rosa rugosa, the flower or leaf of Linden, the whole plant of Malva sylvestris, the leaf or flower of Althaea officinalis, the leaf of Lavatera thuringiaca, the leaf or fruit of Potentilla egedei var. grandis, the whole plant of Lamium purpureum, the leaf or root of Althaea rosea, the leaf or fruit of Rubus idaeus, or the fruit or seed of Fragaria x ananassa Duch.SELECTED DRAWING: None

Description

  The present invention relates to a basal metabolic enhancer containing tyriroside as an active ingredient.

  The autonomic nervous system works automatically regardless of intention, controls various organs, and controls functions such as circulation, breathing, digestion, sweating / temperature regulation, endocrine function, reproduction, and metabolism. The autonomic nervous system regulates various physiological parameters and contributes to the maintenance of homeostasis in cooperation with the endocrine system, which is a regulatory mechanism by hormones. The autonomic nervous system consists of two nervous systems, the sympathetic nervous system and the parasympathetic nervous system, and both often control one organ. Also, both effects on one organ generally work antagonistically. When the body is active, the sympathetic activity is dominant and the whole body is in tension. Conversely, when parasympathetic activity is dominant, the body is in a relaxed state.

  Since the autonomic nervous system controls organs throughout the body, if the balance is lost, various functions may be impaired, such as high blood pressure, palpitation, hot flashes, slight fever, dizziness, tinnitus, gastric ulcer, constipation, diarrhea, chronic fatigue, strong Various symptoms such as anxiety appear. Recently, the balance of autonomic nerves has collapsed, and the number of people with various diseases in terms of physical function and mentality is increasing rapidly. From this point of view, there is a demand for pharmaceuticals or health foods that control autonomic nervous activity. Recently, in order to evaluate autonomic nervous function, heart rate variability power spectrum analysis with high sensitivity and high reproducibility has been performed (Patent Document 1).

  The interval between heart beats (RR interval) is constantly changing (heart rate variability). Since the heart rate variability is caused by the autonomic nerve acting on the heart, the activity state of the autonomic nerve can be evaluated by observing the heart rate variability. The heart rate variability power spectrum is obtained by processing the heart rate variability obtained from the electrocardiogram by fast Fourier transform and performing frequency analysis. The low frequency region (LF, 0.04-0.15 Hz) of the obtained power spectrum shows sympathetic and parasympathetic activity, and the high frequency region (HF, 0.15-0.4 Hz) shows parasympathetic activity. It is believed that. The very low frequency region (VLF, 0.007 to 0.036 Hz) is considered to be involved in the heat production mechanism. The sum (Total) of the power spectra of LF, HF and VLF is considered to reflect the entire autonomic nerve activity mainly occupied by the sympathetic nerve activity.

  Chiloroside is a component contained in plants such as rose hips, and has an action of promoting fat metabolism in vivo and improving glucose tolerance (Patent Documents 2 and 3). However, no effect on the autonomic nervous system has been reported.

JP 2005-320278 A JP 2007-176858 A JP 2010-202594 A

  It is an object of the present invention to provide a basal metabolic enhancer that can act on an autonomic nerve and regulate its function without side effects.

  As a result of intensive studies in order to solve the above-mentioned problems, the present inventors have found that tiliroside has an excellent autonomic nerve regulating effect and completed the present invention.

  The present invention provides a basal metabolism-enhancing agent containing tiliroside as an active ingredient.

  In some embodiments, the Chiloroside comprises rose hips, Naniwaibara berries (gold lions), Hermanus berries or flowers, Linden flowers or leaves, Usbenia mushrooms, Usbenitachai leaves or flowers, Tree Lava It is contained in extracts of terra leaves, leaflet or berries of pearl oysters, whole grass of pearl millet, leaves or roots of hollyhock, raspberry leaves or berries, or fruits or seeds of strawberries.

  The active ingredient of the present invention, tiliroside, changes the function of the autonomic nerve and exhibits an excellent autonomic nerve regulating effect. In particular, it enhances sympathetic nerve activity. Then, symptoms related to autonomic nerve activity can be improved and prevented and / or treated. The tiroloside used in the present invention is a natural component and is safe.

It is a graph which shows the total autonomic nerve activity (Total) of the cardiac autonomic nerve function of the electrocardiogram power spectrum analysis by the rate of change where the power at the Pre time is 1.00. It is a graph which shows the sympathetic nerve activity (LF) of the cardiac autonomic nerve function of the electrocardiogram power spectrum analysis by the rate of change where the power at the Pre time is 1.00.

  The active ingredient of the present invention, tiliroside, is a kind of polyphenol and is represented by the following formula (I).

  The tiroloside is mainly contained in each part of the plant (for example, the whole plant, flowers, stems, bulbs, roots, seeds (pseudofruits), seed coats, etc.). Specifically, rose hips (Rosa canina false fruits), R. laviegata false fruits (gold lions), Hermanus (R. rugosa) false fruits and flowers, linden (Tilia cordata, T. platyphyllos, Or T. argentea flowers and leaves, whole plant of Malva silvestris, leaves and flowers of Althaea officinalis, leaves of Lavatera thuringiaca, leaves and fruits of Potentilla anserina And the whole plant of Lamium purpureum, L. album, leaves and roots of Althaea rosea, leaves and fruits of Rubus idaeus, fruits and seeds of strawberry (Fragaria ananassa). A rose hip is preferable.

  In the present invention, the above-mentioned plant containing tiliroside, a processed product thereof (dried product, ruptured product, shredded product, or dry powder obtained by pulverizing these, or a product obtained by pulverizing and molding the dried product), or extraction thereof The product may be used as tiliroside. In the present specification, the extract means an extract obtained by extracting the plant or a processed product thereof with a solvent, a diluted solution or a concentrated solution thereof, or a dried product thereof. In view of the high degree of purification of tyrilloside, or the point of use as a food or drink or a pharmaceutical composition, it is preferable to use an extract.

  The solvent used for extraction may be a polar solvent or a nonpolar solvent, and is not particularly limited. Examples of such solvents include water; alcohols such as methanol, ethanol, 1-propanol, 2-propanol, 1-butanol, and 2-butanol; ethers such as ether and tetrahydrofuran; esters such as ethyl acetate; Ketones such as acetone; nitriles such as acetonitrile; hydrocarbons such as heptane and hexane; aromatic hydrocarbons such as benzene and toluene; and halogenated aliphatic hydrocarbons such as methylene chloride and chloroform. . These solvents can be used alone or in combination.

  Among the above solvents, alcohol, ethyl acetate, water, and a mixed solvent of two or more thereof are preferably used. As the alcohol, lower alcohols such as ethanol, 1-propanol, 2-propanol, 1-butanol and 2-butanol are preferably used. A mixed solvent of alcohol and water is more preferable. For example, ethanol and water may be used in a volume ratio of 99: 1 to 1:99, preferably 95: 5 to 5:95, and more preferably 70:30 to 30:70. More ethanol is preferable, and for example, 70 v / v (volume / volume)% ethanol (ethanol: water = 70: 30) is also used.

  Although there is no particular limitation on the extraction method, it is preferable that the extraction is performed under conditions as gentle as possible from the viewpoint of safety and convenience in use. For example, the raw material plant part or its dried product is crushed, crushed or shredded, 5 to 20 times the amount of polar or nonpolar solvent is added thereto, and the temperature ranges from 0 ° C. to the reflux temperature of the solvent for 30 minutes to 48 hours. Extraction is performed under conditions such as shaking, stirring or refluxing. An extraction liquid can be obtained by performing separation operations such as filtration and centrifugation after extraction, removing insoluble matters, and performing dilution and concentration operations as necessary. Furthermore, if necessary, the same operation may be repeated for the insoluble matter to further extract, and the extract may be used in combination.

  This extract is used as it is or after being concentrated to form a liquid, a concentrate, a paste, or a dried product obtained by drying these. Drying is performed by a method commonly used by those skilled in the art, such as spray drying, freeze drying, reduced pressure drying, and fluidized drying. The extract may be further purified by a purification method commonly used by those skilled in the art.

  The extract obtained in this manner preferably contains tiroloside in terms of dry mass of 0.01% by mass or more, more preferably 0.02% by mass or more, and further preferably 0.04% by mass or more. The tiliroside in the extract is confirmed by, for example, high performance liquid chromatography.

  Examples of the autonomic nerve regulating action of the autonomic nerve modulating agent of the present invention include sympathetic nerve activity enhancing action, sympathetic nerve activity enhancing action, sympathetic nerve activity inhibiting action, parasympathetic nerve activity enhancing action, parasympathetic nerve activity enhancing action Action, parasympathetic nerve activity inhibitory action, preferably sympathetic nerve activity enhancing action.

  The autonomic nerve regulator of the present invention is a symptom that is likely to occur due to treatment of a disease or condition related to autonomic nerve activity, such as disorder of the autonomic nerve, shortness of breath, palpitation, stiff shoulders, headache, dizziness, anxiety, loss of appetite, Can be used to treat fatigue, insomnia, etc.

  The autonomic nervous regulator of the present invention contains the above-mentioned tiroloside as an active ingredient. This autonomic nerve regulator is mainly used for foods, pharmaceuticals and the like. In humans, the intake of tiroloside is preferably 0.1 to 1 mg, more preferably 0.1 to 0.3 mg per day. What is necessary is just to set suitably according to content of tiroloside, when using a plant extract as tiroloside. For example, the intake of rosehip extract is preferably 100 to 1000 mg in terms of dry mass per day.

  The form of the autonomic nervous regulator of the present invention is appropriately set according to the form of food, medicine, etc. used. For example, it may be formed into a tablet, granule or the like using additives usually used by those skilled in the art (for example, excipients such as dextrin, starch, saccharides, calcium phosphate, fragrances, perfume oils) Alternatively, it may be dissolved in water, beverages or the like to form a liquid. The administration route is not limited, but is preferably oral administration.

  As described above, the autonomic nervous regulator of the present invention is used as a food, a pharmaceutical product and the like. In this case, as long as the autonomic nerve regulating action is not inhibited, the preparation may be combined with a substance having an action different from that of the present invention depending on the symptom.

  EXAMPLES Hereinafter, the present invention will be described in more detail with reference to examples, but the present invention is not limited to these examples.

(Example 1: Preparation of rosehip extract)
A 50 (v / v)% aqueous ethanol solution was added to a dry pulverized product of Chilean rose hip (Rosa canina) fruit (including seeds), followed by reflux extraction at around 90 ° C. The mixture was filtered to remove insolubles, and then ethanol was distilled off under reduced pressure to obtain an extract.

(Example 2: Preparation of rosehip extract preparation)
Powder obtained by drying the extract obtained in Example 1 was mixed with excipient dextrin and cyclic oligosaccharide, and tablets containing 100 mg or 300 mg of tyriloside extract were obtained by a conventional method.

(Example 3: Preparation of tiroloside)
The powder obtained in Example 2 was dissolved in 50 (v / v)% aqueous methanol solution, and this was fractionated under the following condition 1 by reverse phase ODS column chromatography (open column). About the obtained fraction, tiroloside was detected by thin layer chromatography (TLC). In addition, a commercial sample tiliroside (Funakoshi) was used as an index.

(Condition 1)
Column: packed with silica gel (Chromatorex (registered trademark) ODS: manufactured by Fuji silysia Chemical LTD.) (15 cmΦ × 60 cm)
Moving bed: methanol / water (elution is carried out in the order of volume ratios of 50/50, 70/30, and 100/0)

  The fractions in which tiliroside was detected by TLC were combined (referred to as fraction 1). This fraction 1 was further fractionated by normal phase silica gel column chromatography (open column) under the following condition 2. In the same manner as above, fractions in which tiliroside was detected were combined (referred to as fraction 2).

(Condition 2)
Column: packed with silica gel 60N (spherical, neutral) (Kanto Chemical Co., Inc.) (5cmΦ × 40cm)
Moving bed: Trichloromethane / methanol / water (elution is carried out in the order of volume ratios of 15/3/1, 10/3/1, and 7/3/1, and finally with methanol only)

  Fraction 2 was further fractionated under the following condition 3 using a high performance liquid chromatography apparatus equipped with a preparative column and a suggested refractive index detector (RI). The obtained fraction was dried to obtain 67.1 mg of tiliroside.

(Condition 3)
Column: YMC-Pack ODS-A (YMC Co., Ltd.)
Column temperature: Room temperature Moving bed: Acetonitrile / water (volume ratio: 30/70)
Flow rate: 10ml / min

  The obtained tiroloside was mixed with excipient dextrin and cyclic oligosaccharide to obtain a tablet containing 0.1 mg of tiroloside by a conventional method.

(Example 4) Evaluation of an autonomic nerve control effect The autonomic nerve control effect was evaluated as follows using the preparation containing the rosehip extract obtained in Example 2.

  The subjects were 10 healthy female university students. None of the subjects had smoking habits or prescriptions. All measurements were made with a double blind crossover. The subjects randomly took three types of samples (A: placebo; B: rosehip extract (containing 100 mg); C: rosehip extract (containing 300 mg)) with a washout period of 1 week. On each measurement day, subjects woke up at AM 7:00 and took their own breakfast (200 g of white rice) designated at AM 7:30. After coming to the laboratory at 8:45 AM and measuring body composition, he was rested in a sitting position for 30 minutes. Thereafter, an electrocardiogram for 8 minutes and an exhalation gas for 8 minutes were simultaneously measured in a sitting position (Pre). And the sample was ingested with 100 cc of water, and the same measurement as Pre was performed 30 minutes after ingestion (Post30) and 60 minutes after ingestion (Post60).

  The total autonomic nerve activity (Total), sympathetic nerve activity (LF), parasympathetic nerve activity (HF), and VLF of cardiac autonomic nerve function were quantitatively evaluated by electrocardiogram-based heart rate variability power spectrum analysis. For statistical analysis, one-way analysis of variance was performed using statistical processing software SPSS (Statistical Package for Social Science), and Dunnett's t-test was adopted for post-test (Pre vs Post 30, Post 60). The significance probability in the statistical analysis was p <0.05.

  The results of electrocardiogram power spectrum analysis were expressed as the rate of change with the value of Pre being 1.00 (Total: FIG. 1; LF: FIG. 2). In sample B, Total was significantly increased at the point of Post60. In Sample C, Total and LF were significantly increased at the time of Post60, and LF showed a tendency to be higher at the time of Post30.

  From these results, it was found that tiliroside has an action of enhancing total autonomic nerve activity (Total) and sympathetic nerve activity (LF) of autonomic nerve function.

  The basal metabolism enhancing agent of the present invention contains tyriroside as an active ingredient. This tiliroside exerts an excellent autonomic nerve control effect by acting on the autonomic nerve to enhance its activity. In particular, it enhances sympathetic nerve activity and exhibits excellent effects as a preventive and therapeutic agent for various symptoms due to decreased autonomic nervous function. The autonomic nervous regulator of the present invention is used as food, pharmaceuticals and the like.

Claims (2)

  A basal metabolic enhancer containing tiroloside as an active ingredient.   The Chiloroside is Rosehip, Naniwaibara berries, Hermanus berries or flowers, Linden flowers or leaves, Usbenia mushrooms, Usbenitachai leaves or flowers, Tree Lavatera leaves, Ezotsurumkinbai leaves or fruits, The basal metabolism-enhancing agent according to claim 1, which is contained in the whole plant of Giantia pertussis, leaf or root of hollyhock, raspberry leaf or fruit, or fruit or seed of strawberry.

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