JP2007297370A - Suppressor of increase in blood glucose level - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To specify a substance having a higher effect among many reported chemical substances derived from natural materials which can suppress the increase in blood glucose level, and to provide a suppressor for the increase in blood glucose level which is free from the concern of deterioration in odor or flavor and is also free from the concern of adverse side-effects. <P>SOLUTION: The suppressor comprises fucoxanthin as an active ingredient. Fucoxanthin may be added to a food, a beverage, a nutritional supplement, a pet food, a sanitary product, a cosmetic or a pharmaceutical product. Fucoxanthin may be selected from one extracted/purified from a natural material, one produced by organic synthesis and one synthesized in a microorganism and may be used alone or in combination. <P>COPYRIGHT: (C)2008,JPO&INPIT

Description

  The present invention relates to a blood sugar level increase inhibitor comprising fucoxanthin as an active ingredient.

  Currently, it is said that there are over 10 million potential diabetic patients in Japan including the Diabetes Reserve. In diabetes, the blood sugar level (blood glucose level) rises excessively, and the insulin secretion function that regulates the blood glucose level does not work normally. Therefore, in order to reduce the blood sugar level, prescriptions such as coping therapy such as exercise and dietary restrictions and insulin injection have been made. Recently, a method of taking a substance that suppresses an increase in blood glucose level has also been adopted.

  As chemical substances derived from natural products that suppress an increase in blood glucose level, various substances such as Chinese herbal medicine components and higher plant components have been reported (Non-Patent Documents 1-4). Furthermore, many components that suppress the increase in blood glucose level have been found in substances contained in seaweed. For example, it has been reported that polysaccharides such as fucoidan and alginic acid have physiological functions such as a blood glucose level increase inhibitory effect and a blood lipid increase inhibitory effect (Patent Documents 1-6).

  Substances assumed as a blood glucose level increase inhibitor in the patent documents include fucoidan, fucoidan decomposition product, fucoidan salt, fucoidan decomposition product salt, sodium alginate, seaweed polysaccharide containing all of the above substances in a broad sense, and the substance in a broad sense. It is a seaweed powder containing. Generally, seaweed contains these water-soluble components extracted with hot water, acid, alkaline aqueous solution, or the like, and fat-soluble components extracted with an organic solvent such as ethanol. With regard to water-soluble components, the proportion of seaweed in the seaweed is overwhelmingly large, so there is a history of its extensive application. On the other hand, regarding fat-soluble components, the proportion in seaweed is as low as about 1%, and until recently, physiological activity has hardly been investigated.

  Fucoxanthin, one of the fat-soluble substances contained in seaweed, is a kind of carotenoid, and is one of the most common carotenoids along with β-carotene. However, even if the amount of fucoxanthin contained in seaweed is large, it is about 0.1% by weight with respect to dry seaweed, and so far, its physiological function has hardly been investigated.

  In recent years, various physiological functions of fucoxanthin have been highlighted and various reports have been made. Examples thereof include an anti-obesity action (Non-Patent Document 5) and an apoptosis-inducing action on cancer cells (Non-Patent Documents 6 and 7). However, the physiological effect of fucoxanthin on the blood glucose level has not been reported at present in either patent literature or non-patent literature. As described above, there has been a report on the blood glucose level increase inhibitory effect using seaweed powder or seaweed extract. However, since the content of fucoxanthin in seaweed is very low, this blood glucose level increase inhibitory effect is fucoxanthin. Rather, it is reasonable to think that it is due to seaweed polysaccharides.

  However, when using seaweed powder or seaweed extract to suppress the increase in blood glucose level, it is not specified which substance is effective in suppressing the increase in blood glucose level, so it is necessary to consume a large amount of seaweed powder or seaweed extract. was there. Furthermore, when seaweed powder or seaweed extract is used, there is a problem that the smell and flavor peculiar to seafood are shifted to foods and beverages to be added. For Japanese people who are accustomed to eating fish and shellfish and seaweed, the smell and flavor peculiar to seafood is not a big problem, but it is a big problem for Westerners who are not in such a custom. In addition, there were concerns about side effects when using a chemically synthesized drug that had the effect of suppressing an increase in blood glucose level.

T. Nishiyama et al., Journal of Agricultural and Food Chemistry, 53 (2005) 959-963. A. Hattori et al., J. Nutr. Sci. Vitaminol, 51 (2005) 382-384. T. Miura et al., Biol. Pharm. Bull., 27 (2004) 248-250. Morimoto et al., Yakugaku Zasshi, 122 (2002) 163-168. H. Maeda et al., Biochemical and Biophysical Research Communication, 332 (2005) 392-397. Hosokawa, BIO INDUSTRY, 21 (2004) 52-57. I. Konishi et al., Comparative Biochemistry and Physiology. Part C, Pharmacology, toxicology & endocrinology, 142 (2006) 53-59. No. 2002-022140 JP 2004008165 A JP 2004-329047 A JP 2003-304830 A JP 2002-212201 A JP 2001-226275 A

  The present invention has been made in view of the problems of the prior art, and has identified a highly effective substance among chemical substances derived from natural products that suppress the increase in blood glucose level, which has been reported in large numbers. An object of the present invention is to provide an agent for suppressing an increase in blood glucose level, which does not have a problem of flavor and is free from side effects.

    As a result of intensive studies on the above problems, the present inventors have suppressed fucoxanthin, which is a typical phenomenon at the onset of diabetes, to increase the amount of drinking water, and to reduce blood sugar levels depending on the amount of fucoxanthin added. I found That is, a substance having a large effect was identified from among chemical substances derived from natural products that suppress the increase in blood glucose level that has been reported in large numbers. Therefore, by using fucoxanthin as an active ingredient, it has become possible to effectively suppress an increase in blood glucose level. In addition, fucoxanthin has no odor or flavor peculiar to seaweed, so even if it is added to any food, beverage, etc., these odor and flavor are not impaired. This fucoxanthin is a component contained in seaweeds such as seaweed, and since it has been eaten by Japanese since ancient times, it can be safely used.

  That is, the blood sugar level elevation inhibitor of the present invention is characterized by containing fucoxanthin as an active ingredient.

  Furthermore, the blood sugar level elevation inhibitor of the present invention is characterized in that fucoxanthin is added to any of foods, beverages, supplements, pet foods, cosmetics, sanitary products, and drugs.

  The fucoxanthin may be in a powder state, in a solid state, dissolved in an organic solvent, or water-soluble using a surfactant.

The fucoxanthin was obtained by one or a combination of two or more selected from components extracted from natural products and purified, components obtained by organic synthesis, and components synthesized through microorganisms. It may be a thing.

  According to the present invention, an increase in blood glucose level can be suppressed by using fucoxanthin as an active ingredient. Furthermore, fucoxanthin has no odor or flavor peculiar to seaweed, so even when fucoxanthin is added to foods, beverages, supplements, etc. There is no problem of smell or flavor. Further, fucoxanthin is a component contained in seaweed that has been eaten since ancient times, and can be used healthily and safely, and there is no problem of side effects. Therefore, it is possible to suppress an increase in blood glucose level by including fucoxanthin as an active ingredient in foods, beverages, supplements, pet food, sanitary products, cosmetics and pharmaceuticals.

  Hereinafter, embodiments of the present invention will be specifically described with reference to the drawings. However, the present invention is not limited only to the embodiments.

For example, fucoxanthin extracted from dried wakame powder and isolated and purified using column chromatography can be used.
Fucoxanthin added in this way is not limited to those extracted from seaweed, but extracted from natural products including marine products, purified, obtained by organic synthesis, synthesized through microorganisms It does not matter. Or what was obtained by the combination of 2 or more types chosen from them may be used.

  In addition, in order to efficiently add fucoxanthin to foods, beverages, supplements, pet food, sanitary products, cosmetics and pharmaceuticals, it is possible to use what is dissolved in an organic solvent such as ethanol, or a surfactant (emulsifier). It is also possible to make it water-soluble. That is, the form of fucoxanthin to be added, that is, the chemical / physical state may be any state.

  In addition, the anti-obesity effect including the fat accumulation effect (nonpatent literature 5) and the reduction effect of blood lipid can be anticipated as effects other than suppression of a blood glucose level increase by addition of fucoxanthin. That is, by ingesting fucoxanthin, not only the increase in blood sugar level but also various health enhancements can be achieved. In addition, it is estimated that the increase in blood glucose level can be suppressed by fucoxanthin because the control of insulin secretion has been improved in some way.

[Example 1]
Hereinafter, although an example of the present invention is described concretely, referring to drawings, the present invention is not limited only to this example.
(Animal experiments using diabetic model mice)
Three-week-old female KK-Ay mice were purchased from Nippon Claire Co., Ltd. as a diabetes onset model mouse, and experimental breeding was performed after one week of preliminary breeding. Mice were bred under conditions of a temperature of 23 ± 1 ° C., a humidity of 55 ± 10%, and lighted from 7 am to 7 pm (others were extinguished). The time represents Japan time unless otherwise noted. During breeding, food and water were freely consumed. The feed was based on the AIN-93G composition (one of the standard compositions for breeding experiments published by the National Institute of Nutrition).

  AIN-93G contains 13.5% by weight of soybean oil. Those containing 13.5% by weight of soybean oil were used as the control group, of which 0.1% by weight and 0.2% by weight were substituted with fucoxanthin, respectively, 0.1% fucoxanthin administration group, 0.2% The fucoxanthin administration group was used. The fucoxanthin used here was extracted from dried wakame powder and isolated and purified using column chromatography.

  In this example, the amount of soybean oil in the feed replaced with fucoxanthin was shown as 0.1% and 0.2% in weight ratio, but the weight ratio was further increased. Can be smaller.

  The control group, the 0.1% fucoxanthin added group, and the 0.2% fucoxanthin added group were bred on the experimental diet for 26 days after 7 weeks of each group for 1 week of preliminary breeding. The total amount of drinking water was measured for 3-10 days, 11-18 days, 19-26 days, and 19-26 days after the start of experimental breeding. The blood glucose level was collected from the tail vein between 10:00 am and 12:00 am in the non-fasted state on the 25th day after the start of experimental breeding, and was measured using a commercially available blood glucose level test apparatus. In this example, the fucoxanthin-added food was ingested continuously for 26 days, but the ingestion period is not particularly limited to this example, and may be intermittently performed.

  FIG. 1 shows the amount of water consumed per week in KK-Ay mice given experimental samples, and FIG. 2 shows the amount of water consumed per day in week 4 of KK-Ay mice. 1 and 2, the vertical axis represents the amount of drinking water (mL). In general, there are many physiological phenomena in which the amount of drinking water increases with the onset of diabetes. According to Non-Patent Document 4, “In diabetes, urine sugar increases the osmotic pressure in the tubule, so that reabsorption of water is suppressed and the amount of urine increases, resulting in a decrease in tissue water content. It is explained that severe thirst occurs and water consumption increases. " In this example, when comparing the amount of water consumed between the control feed group, the 0.1% fucoxanthin-added feed group, and the 0.2% fucoxanthin-added feed group, the fucoxanthin-added feed group was more per week and per day. In both cases, there was a decrease in water consumption. From these results, it was found that the intake of fucoxanthin-added feed can suppress an increase in water consumption, which is a physiological phenomenon at the onset of diabetes.

  In addition to this indirect investigation, blood glucose levels of KK-Ay mice raised in each group on the 25th day after actually ingesting the experimental feed were also measured. FIG. 3 shows blood glucose levels of KK-Ay mice 4 weeks after feeding the experimental feed. The vertical axis represents blood glucose level (mg / mL). As shown in FIG. 3, in the group fed with the fucoxanthin-added feed, a phenomenon of a decrease in blood glucose level was observed depending on the concentration of fucoxanthin. This direct decrease in blood glucose level is consistent with the previously reported indirect decrease in water consumption.

  In the fucoxanthin addition group, as an effect other than the above-described suppression of the increase in blood glucose level, an anti-obesity effect including a fat accumulation effect (Non-Patent Document 5), which has been reported as a physiological effect of fucoxanthin, and a blood lipid reducing effect It was observed.

From the above examples, it was confirmed that fucoxanthin has an action of suppressing an increase in blood glucose level.
[Example 2]
1. Rearing
C57 / BL6J mice (male; 9 weeks old) were used to confirm the effect of adding the inhibitor for increasing blood glucose level of the present invention.
The test food was prepared according to AIN-93G composition. Mice were obese by pre-feeding for 10 weeks on a high fat diet (mixed fats such as lard and soybean oil: 30%). After pre-breeding, high fat diet group (mixed fat: 30%), fucoxanthin added group-1 (mixed fat (30%) + fucoxanthin (0.1%), fucoxanthin added group-2 (mixed fat (30%)) + Fucoxanthin (0.2%) was raised for 4 weeks.

The breeding room temperature was 23 ± 1 ° C., the humidity was 50%, and the brightness was set to 12 hours. Feed and water were ad libitum.
After the feeding period, they were fasted for 12 hours. Subsequently, blood was collected under EDTA from the neck under ether anesthesia. The organs were removed immediately after blood collection, washed thoroughly with physiological saline, and thoroughly exsanguinated. The liver was weighed and stored at −40 ° C. until analysis. RNA was extracted from skeletal muscle, and the expression level of glucose transporter 4 (GLUT4) was measured by real-time PCR.

2. Analysis FIG. 4 shows the measurement results of blood glucose levels in the blood of the high fat diet group, the fucoxanthin addition group-1 and the fucoxanthin addition group-2, which were bred by administering only the high fat diet.
It can be seen that the blood glucose level in the blood was significantly reduced by administration of fucoxanthin compared to the high fat diet alone. This result is the same as the conventional diabetic mouse (KK-Ay mouse).
Fig. 5 shows the expression level of glucose transporter 4 (GLUT4) in the muscles of the high-fat diet group, the fucoxanthin-added group-1 and the fucoxanthin-added group-2 that were fed with the high-fat diet. The results are shown in comparison.
As shown in FIG. 5, it was found that GLUT4 was significantly increased by administration of fucoxanthin. From this, it was clarified that the blood glucose level reducing action by fucoxanthin is caused by the increase of GLUT4 in the muscle and the accompanying uptake of sugar from blood into the muscle and promotion of consumption.

3. GLUT4 Expression in Skeletal Muscle Cells FIG. 6 shows a comparison of the results of measuring the gene expression level of GLUT4 in skeletal muscle cells (L6) to which fucoxanthin was added and skeletal muscle cells (L6) to which fucoxanthin was not added. As shown in FIG. 6, the gene expression level of GLUT4 was significantly increased in the skeletal muscle cells (L6) to which fucoxanthin was added as compared to the skeletal muscle cells (L6) not added. This indicates that fucoxanthin increases GLUT4 activity in skeletal muscle, and thereby exhibits an anti-diabetic effect by promoting sugar uptake and consumption.

  The present invention relates to a blood sugar level increase inhibitor comprising fucoxanthin as an active ingredient. Therefore, it can be used as a functional food material by adding fucoxanthin to a food material and the like in the medical field, and can be expected to be used in the agricultural field.

1 shows the amount of water consumed per week in KK-Ay mice fed with experimental feed, according to Example 1, which is an example of the blood sugar level elevation inhibitor of the present invention. Explanatory drawing which shows that there exists a significant difference compared with a control group (P <0.01). It relates to Example 1 which is an example of the blood sugar level elevation inhibitor of the present invention, and shows the amount of water consumed per day on the 19th to 26th day of KK-Ay mice. The fucoxanthin administration group has any administration level. Explanatory drawing which shows that there exists a significant difference compared with a control group (P <0.01). It relates to Example 1 which is an example of the blood sugar level elevation inhibitor of the present invention, and shows the blood sugar level of KK-Ay mice on the 25th day after feeding the experimental feed. The fucoxanthin administration group has any administration level. Explanatory drawing which shows that there is also a significant difference compared with a control group (P <0.01). In connection with Example 2 which is an example of the blood sugar level increase inhibitor of the present invention, the measurement results of blood glucose levels in the blood of the high fat diet group and the fucoxanthin addition group are shown in comparison, Explanatory drawing which shows that a significant difference is recognized by the fucoxanthin addition group compared (P <0.01). The comparison of the gene expression level of glucose transporter 4 (GLUT4) in the muscles of the high fat diet group and the fucoxanthin addition group is shown in comparison, and is significantly more significant in the fucoxanthin addition group than in the high fat diet administration group Explanatory drawing which shows that a difference is recognized (P <0.01). ) GLUT4 gene expression levels in skeletal muscle cells (L6) with and without fucoxanthin were compared and compared with skeletal muscle cells (L6) without fucoxanthin. Explanatory drawing which shows that a significant difference is recognized by the skeletal muscle cell (L6) which added fucoxanthin (P <0.05).

Claims (6)

  A blood sugar level increase inhibitor comprising fucoxanthin as an active ingredient.   A blood sugar level increase inhibitor comprising fucoxanthin added to any of foods, beverages, supplements, pet food, cosmetics, sanitary products and drugs.   The blood glucose level increase inhibitor according to claim 1 or 2, wherein the fucoxanthin is in a powder state, a solid state, or a combination thereof.   The blood sugar level increase inhibitor according to claim 1 or 2, wherein the fucoxanthin is dissolved in an organic solvent.   The blood glucose level increase inhibitor according to claim 1 or 2, wherein the fucoxanthin is water-soluble using a surfactant.     The fucoxanthin is obtained by one or a combination of two or more selected from components extracted from natural products and purified, components obtained by organic synthesis, and components synthesized through microorganisms. The blood glucose level elevation inhibitor according to any one of claims 1 to 5.

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