JP2016108242A - Blood parameter improving agent - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a blood parameter improving agent containing Zanthoxylum piperitum ingredient as an active ingredient, and to provide a composition containing it.SOLUTION: An excellent blood parameter improving agent can be provided by incorporating into a composition for oral administration, such as foods and pharmaceuticals, the Zanthoxylum piperitum extract in which blood lipid and sugar parameters are improved by the acceleration of the differentiation of adipocytes.SELECTED DRAWING: None

Description

The present invention relates to a blood parameter improving agent using a salamander extract.

Metabolic syndrome in which lifestyle-related diseases such as dyslipidemia and diabetes are accumulated in one individual is a disease that has become a social problem with an increasing number of patients in recent years. This condition eventually causes arteriosclerosis and is said to cause heart disease and cerebral infarction, which occupy the second and third most common causes of death in Japan. Therefore, development and discovery of materials for treating or preventing metabolic syndrome are desired.

In order to treat or prevent such metabolic syndrome, it is necessary to simultaneously improve a plurality of lifestyle-related diseases such as dyslipidemia and diabetes. In addition, lifestyle-related diseases are diseases that are greatly affected by normal lifestyle, and treatment takes time. Therefore, it is desirable to use a material with abundant dietary experience that is safe even if taken for a long time.

Salamander is a highly safe material because it has a rich dietary experience and has been used as a raw material for traditional Chinese medicine since ancient times.
Regarding the functions of salamander, lipase inhibitory effect (Patent Document 1) and salty taste enhancing effect (Patent Document 2) have been reported, but salamander extract promotes the differentiation of adipocytes and has an effect of improving blood parameters. It is not known to have.

JP2002-179586 JP2011-254772

An object of the present invention is to provide an agent for improving blood triglyceride levels and blood glucose levels, which are metabolic syndrome-related blood parameters, using salamander extracts with abundant dietary experience.

As a result of intensive research efforts, the present inventors have found that a polar solvent extract of dried salamander fruit reduces blood parameters by promoting adipocyte differentiation. That is, the present invention relates to the following technique.
Item 1. A blood parameter improving agent comprising an extract of Citrus salamander as an active ingredient.
Item 2. The blood parameter improving agent according to Item 1, wherein the blood parameter is a blood triglyceride value.
Item 3. The blood parameter improving agent according to Item 1, wherein the blood parameter is a blood glucose level.
Item 4. The blood parameter improving agent according to Item 1, wherein the blood parameters are a blood triglyceride value and a blood glucose value.
Item 5. The blood parameter improving agent according to any one of Items 1 to 4, wherein the blood parameter improving effect is based on the promotion of adipocyte differentiation.
Item 6. The blood parameter improving agent according to Item 1 to 5, wherein the extract is a polar solvent extract and / or a solvent-removed product of Citrus salamander fruit.
Item 7. A composition for oral administration containing the blood parameter improving agent according to any one of Items 1 to 6.

  The metabolic syndrome-related blood parameter improving agent of the present invention increases normal small fat cells and activates lipid and sugar metabolism by promoting differentiation from preadipocytes to adipocytes. Therefore, it is considered that it exhibits preventive and therapeutic effects on lifestyle-related diseases such as diabetes and dyslipidemia caused by an increase in enlarged fat cells.

FIG. 1 is an image obtained by staining 3T3-L1 cells, to which a salamander extract has been added and induced to differentiate, with OiL Red O staining. Example 1 FIG. 2 is a graph showing the absorbance of the 3T3-L1 cell dye extract of FIG. Example 1 FIG. 3 is a graph showing changes in body weight of mice fed with salamander. (Example 2) FIG. 4 is a graph showing the triglyceride levels in the blood of mice 60 days after administration of the salamander diet. (Example 2) FIG. 5 is a graph showing mouse blood glucose levels 60 days after administration of the salamander diet. (Example 2)

Hereinafter, the present invention will be described in detail.
(1) Salamander Varieties Among the salamander extracts of the present invention, among the salamanders (Zanthoxylum), salamander (Zanthoxylum piperitum), kahoku salamander (Zanthoxylum simulans Hance.), Fin salamander (Zanthoxylum beecheyanum), Zanthoxylum americanum, Zanthoxylum simulana, Zanthoxylum schinifolium, Zanthoxylum ailanthoides, Zanthoxylum armatum, Zanthoxylum piperium f. Inerme (Zanthoxylum piperium f. Brevispinum) can be used, and among them, it is particularly preferable to use a salamander (Zanthoxylum piperitum).

(2) Salamander extract The salamander extract of the present invention is an extract of a salamander plant itself, a processed product obtained by drying, chopping, or pulverizing the plant, or extracting the plant or the processed product with a solvent. It is a generic term for a product, a solvent-removed product from which the solvent has been removed, or an extract or a purified fraction obtained by purifying the solvent-removed product by column chromatography or liquid-liquid extraction. In addition, although an extract can be extracted from the whole plant of a plant body, a fruit part can illustrate especially preferable. In addition, the plant body may be used as it is, or may be used as a dried body obtained by drying, but the dried body is particularly preferable. Among these, as the blood parameter improving substance of the present invention, a solvent extract of dried salamander or a solvent-removed product thereof can be preferably exemplified, and a polar solvent can be particularly preferably exemplified as such a solvent. Examples of such polar solvents include water, ethanol, methanol and other alcohols, ethyl acetate and methyl formate esters, ketones such as acetone and methyl ethyl ketone, halogenated hydrocarbons such as chloroform and methylene chloride, Preferred examples include one or more selected from nitriles such as acetonitrile and ethers such as diethyl ether and tetrahydrofuran. Of these, water or alcohol is particularly preferable. In order to prepare such an extract, a 1 to 10-fold amount of a solvent is added to a plant body or a processed product, and the mixture is immersed for one day at room temperature. Thereafter, the insoluble matter is removed by filtration or the like, and the solvent can be removed by vacuum concentration or lyophilization as necessary. In the case of dried fruit of salamander, it is particularly preferred as an essence to extract 70% ethanol, then filter, concentrate under reduced pressure, and optionally freeze-dry.

(3) Blood parameter improver The blood parameter improver of the present invention contains the above-described salamander extract of the present invention as an active ingredient. The agent of the present invention can be used as a pharmaceutical, a quasi-drug, or a food composition.
Pharmaceutical formulation The agent of this invention can be made into the formulation which has various oral administration forms. Examples of solid preparations include powders, granules, tablets, tablets, pills, capsules, chewable agents and the like. Examples of the liquid preparation include emulsions, solutions, syrups and the like.
The solid preparation is prepared by blending a pharmaceutically acceptable carrier or additive with the above-mentioned salamander extract which is an active ingredient. For example, excipients such as sucrose, lactose, glucose, starch, mannitol; binders such as gum arabic, gelatin, crystalline cellulose, hydroxypropylcellulose, methylcellulose; disintegrants such as carmellose, starch; anhydrous citric acid Stabilizers such as sodium laurate and glycerol are blended. Further, it may be coated or encapsulated with gelatin, white sugar, gum arabic, carnauba wax or the like. The liquid preparation is prepared, for example, by dissolving or dispersing the fraction of strawberry fruit in water, ethanol, glycerin, simple syrup, or a mixture thereof. In these preparations, additives such as sweeteners, preservatives, demulcents, diluents, buffers, flavoring agents, and coloring agents may be added.

Food Composition When the agent of the present invention is a food composition, the food composition is suitable for use as a dietary supplement (supplement). In particular, it can be suitably used as a health functional food (food for specified health use, nutritional functional food).
This food composition is blended with excipients or additives usually used in foods, tablets, tablets, pills, granules, powders, powders, capsules, wettable powders, emulsions, liquids, extracts. Or a dosage form such as an elixir.
Common excipients used in food include syrup, gum arabic, sucrose, lactose, powdered reduced maltose, cellulose sugar, mannitol, maltitol, dextran, starches, gelatin, sorbit, tragacanth, polyvinylpyrrolidone Agents; sucrose fatty acid esters, glycerin fatty acid esters, magnesium stearate, calcium stearate, talc, polyethylene glycol, etc .; disintegrants such as potato starch; wetting agents such as sodium lauryl sulfate. Examples of additives include fragrances, buffers, thickeners, colorants, stabilizers, emulsifiers, dispersants, suspending agents, preservatives, and the like.

The food composition of the present invention may be a general beverage, food, or seasoning composition.
Examples of the beverage include sports beverages, drinks, milk beverages, lactic acid bacteria beverages, fruit juice beverages, carbonated beverages, vegetable beverages, tea beverages, coffee beverages, and alcoholic beverages.
As food, processed grains such as noodles and bread crumbs; processed beans such as miso; dairy products such as yogurt and cheese; processed vegetables and fruits such as jam, pickles and boiled rice; rice flour, flour, Powder such as kinako; dried food such as instant noodles and instant soup; retort food such as soup and curry; confectionery such as cookies, biscuits, snacks, jelly, gum, gummi, candy, chocolate and ice cream Is mentioned.

Seasonings include ketchup, mayonnaise, dressing, soy sauce, sauce, soup and sauce.
This food composition also includes liquid, paste, or salamander extract itself, and can be ingested by adding it directly to the meal.

Hereinafter, the present invention will be described in more detail with reference to examples, but it goes without saying that the present invention is not limited to such examples.
<Production example>
For the extract of dried fruit of salamander, 100 mL of 70% ethanol was added to 10 g of dried fruit of zanthoxylum piperitum, extracted at room temperature for 1 day, filtered to remove insoluble matters, and further concentrated under reduced pressure. Thereafter, it was freeze-dried. And the salamander extract which is a blood parameter improving agent of this invention was obtained.

<Example 1>
About each salamander extract obtained by the manufacture example, the adipocyte differentiation promoting effect was measured as follows.
Mouse-derived preadipocytes 3T3-L1 were cultured at 37 ° C. in a DME medium (Dulbecco's modified Eagle medium) containing 10% fetal calf serum using a 6-well multiplate. The medium was changed every 2 days. After the cells reached a dense state, differentiation was induced with the following representative reagents. That is, differentiation induction treatment was performed by adding three kinds of mixed solutions of dexamethasone, methylisobutylxanthine and insulin to the medium. At this time, the salamander extract obtained in the production example was added. The differentiation induction treatment was carried out for 2 days, and then the culture was continued in the original medium, but the salamander extract obtained in the production example was continuously added when the medium was changed. About one week later, lipid droplets in the cells, which are indicators of differentiation into adipocytes, were observed by OiL Red O staining. When preadipocytes differentiate and become adipocytes, lipid droplets are formed within the cells. Since OiL Red O staining stains intracellular lipid droplets, the degree of differentiation of adipocytes can be visually determined. In addition, after staining with OiL Red O staining, the cells are washed thoroughly and then extracted with isopropanol, so that OiL Red O pigment trapped in the lipid droplets can be extracted and compared by a colorimetric method. The measurement was performed together.

  The results are shown in FIGS. FIG. 1 is an image showing an OiL Red O-stained image 8 days after differentiation induction with the addition of the salamander extract obtained in Production Example at various concentrations. FIG. 2 is a graph comparing the absorbance of the solution after extraction with isopropanol measured at OD 510 nm. The numerical values in the figure are relative values obtained by comparing measured values of various concentrations of the salamander extract added group, where the ethanol added group used as the solvent control is 1. As is clear from FIG. 1, the ratio of cells differentiated into fat cells was increased by the addition of the salamander extract obtained in the production example. Further, as apparent from FIG. 2, the differentiation promoting effect was promoted depending on the concentration of the salamander extract.

<Example 2>
A group of 6 C57BL / 6 male mice of 5 weeks of age, normal feed AIN-93M (Oriental Yeast Co., Ltd.), fat 60% calorie ratio high fat feed HFD-60 (Oriental Yeast Co., Ltd.), HFD Mice were allowed to freely ingest a diet supplemented with low concentration (1%) or high concentration (3%) of dried fruit powder of Zanthoxylum piperitum at -60 as a test substance for 60 days. Meanwhile, the body weight of the mice was measured every two days. Thereafter, the triglyceride level and glucose level in plasma were measured.

As shown in FIG. 3, weight gain was suppressed in those to which dried salamander fruit powder was added compared to the HFD-60 alone administration group. Moreover, the effect was promoted with the increase of salamander dose. From this, it can be seen that the salamander powder has an obesity suppressing effect.

As shown in FIGS. 4 and 5, blood triglyceride and blood glucose levels were lower in those to which dried salmon fruit powder was added compared to the HFD-60 alone administration group. In addition, these blood parameters were reduced to the same level or lower in the low concentration salamander administration group in an obese state as in the AIN-93M administration group, which is a normal diet. From the above results, it has been clarified that blood parameters are improved even when obesity has not been improved by the effect of promoting fat cells of salamander.

The salamander extract of the present invention is made from salamander with abundant food experience and is highly safe even if ingested for a long time. Moreover, since it has an adipocyte differentiation promoting action, it lowers blood triglyceride levels and / or blood glucose levels. Therefore, the salamander extract of the present invention can be suitably used for prevention or improvement of metabolic syndrome requiring long-term treatment.

Claims (7)

A blood parameter improving agent comprising a salamander extract as an active ingredient. The blood parameter improving agent according to claim 1, wherein the blood parameter is a blood triglyceride value. The blood parameter improving agent according to claim 1, wherein the blood parameter is a blood glucose level. The blood parameter improving agent according to claim 1, wherein the blood parameters are a blood triglyceride value and a blood glucose value. The blood parameter improving agent according to claim 1, wherein the blood parameter improving effect is based on the promotion of differentiation of adipocytes. The blood parameter improving agent according to claim 1, wherein the extract is a polar solvent extract of salamander fruit and / or a solvent removed product thereof. The composition for oral administration containing the blood parameter improving agent of any one of Claims 1-6.