JP4553604B2 - Function enhancing composition for general food, health functional food or health supplement and method thereof - Google Patents

Description

  The present invention relates to a function-enhancing composition that improves the bioavailability of active ingredients of general foods, health functional foods, or health supplements by components that perform intestinal environment maintenance and / or antioxidant capacity maintenance, and their functions It is related with the enhancement method.

  In recent years, attention has been focused on improving dietary habits and intake of functional health foods and health supplements due to the growing health appeal. Functional health foods are foods (nutrient functional foods, foods for specified health use) that have been approved by the government to display health functions and nutritional functions based on standards and individual examinations that take into consideration effectiveness and safety. is there. Health supplements are so-called health foods, including foods containing functional ingredients, foods enriched with functional ingredients, foods combining functional ingredients, and nutritional supplements (so-called supplements). . The purpose of these health promotion behaviors is disease prevention / risk reduction, QOL (Quality of Life) improvement, beauty / diet, etc., and various products are proposed in the market.

  On the other hand, we maintain life activities by ingesting various foods in our daily lives. These ingested foods are digested and absorbed as they pass through the gastrointestinal tract, circulate through the body through body fluids such as blood, and are used or converted where needed. However, it is said that their physiological functions are reduced by aging and lifestyle habits (stress, environmental pollution, lack of exercise, etc.) and cause deterioration of in vivo utilization efficiency.

  For this reason, even if you try to have a well-balanced diet and supplement nutrients and functional ingredients with health functional foods and health supplements, the expected effects are often difficult to achieve. There is a concern that the situation will not be achieved. In addition, considering the deterioration of in vivo use efficiency, many products are over-designed because they are considered to be more effective if they are consumed more. There is also concern that the negative side will come out as a result.

  In such a situation, several attempts have been made. For example, as for absorption, mineral absorption is promoted by ingestion of fructooligosaccharide, and pathological symptoms due to its deficiency are improved (see, for example, Patent Documents 1 and 2). In addition, it is known to show synergistic effects on isoflavone absorption promotion and osteoporosis by ingesting fructooligosaccharides (see, for example, Patent Document 3). Regarding circulation, an increase in skin blood flow due to intake of vitamin E is known (see, for example, Non-Patent Document 1). Moreover, the blood pressure fall by intake of vitamin C is known (for example, refer nonpatent literature 2).

However, these reports are evaluations of individual absorption enhancements or are limited to only a part of the blood circulation (coronary circulation, muscle circulation, skin circulation, cerebral circulation, etc.). is there. Therefore, there has been no development of functional enhancement compositions for general foods, health functional foods, or health supplements that improve the bioavailability of nutrients and functional ingredients universally by improving the functions of digestion, absorption and circulation in the body. Absent.
Patent No. 3024896 Japanese Patent No. 31885853 International Publication No. WO99 / 44621 Tanaka S., Jikeikai. Med. J., 1994, 41, p.367-387 Mullan BA et al., Hypertension, 2002, 40, p.804-809

  In view of the above situation, the present inventors have conducted extensive research on digestion / absorption and improvement of the internal circulation, and as a result, probiotics (the host animal by improving the balance of intestinal flora formed by intestinal microorganisms). For example, yogurt containing lactic acid bacteria can be used as a representative, or prebiotics (promoting the growth of useful bacteria in the intestine or suppressing the growth of harmful bacteria) Is an indigestible food ingredient that has an advantageous effect on the health of the host animal, such as oligosaccharides and dietary fiber, and biogenics (directly or via intestinal microorganisms) It is a food component that shows activity, for example, intestinal environmental maintenance by ingestion of whey fermented product as a representative), vitamins and Improve the basic biological functions of digestion, absorption, circulation, metabolism, and immunity through the maintenance of antioxidant capacity through the intake of rotenoids, minerals, and antioxidant food ingredients, thereby improving the production of general foods, health functional foods, and health supplements. As a result, the present inventors have found a composition that contributes to health that enhances the efficiency of use in the body and, as a result, enhances the functions of these foods. The present invention has been completed based on the accumulation of such new knowledge.

  That is, the present invention relates to a function-enhancing composition that improves the in-vivo efficiency of active ingredients of general foods, health functional foods, or health supplements by components that maintain the intestinal environment and / or antioxidant capacity, and those This is a function enhancement method.

  In addition, the present invention provides an active ingredient for general foods, health functional foods, or health supplements, including one or more of the components that maintain the intestinal environment, which are probiotics, prebiotics, and biogenics. A function-enhancing composition that improves the in-vivo utilization efficiency and a method for enhancing these functions.

  Furthermore, the present invention provides an active ingredient for general foods, health functional foods, or health supplements, which contains one or more lactic acid bacteria, oligosaccharides, dietary fiber, or bifidobacterial growth factor as components for maintaining the intestinal environment. It is the function enhancement composition which improves in-vivo utilization efficiency, and those function enhancement methods.

  As another aspect, the present invention provides a general food, a health functional food, or a health supplement, wherein the component for improving antioxidant capacity includes one or more of vitamins, carotenoids, minerals, or antioxidant food components. It is the function enhancement composition which improves the bioavailability of the active ingredient of these, and those function enhancement methods.

  Furthermore, as another aspect, the present invention relates to a general food, a health functional food, or a health supplement characterized by ingesting the function enhancing composition in advance before ingesting a general food, a health functional food, or a health supplement. This is a method for enhancing the function of food.

  Further, the present invention is a function enhancing method for general foods, health functional foods, or health supplements, characterized in that the general foods, health functional foods or health supplements and the function enhancing composition are ingested simultaneously.

  The active ingredient of the food in the present invention refers to a nutrient or a functional ingredient (a component having no nutritional component aspect and having only a physiological function. Specifically, an antioxidant such as polyphenol, lactoferrin, etc. In-vivo efficiency means that nutrients or functional ingredients are digested, absorbed and delivered to the place where they are used and processed, and how they are used and processed Or that efficiency.

    Intestinal environment maintenance in the present invention means that by ingesting a component containing one or more of probiotics, prebiotics and biogenics, useful bacteria grow in the intestines and organic acids are produced. This means that the organic acid promotes digestion, absorption, or metabolic function by regenerating the intestinal mucosa and suppressing harmful bacteria.

Probiotic components for maintaining the intestinal environment include Bifidobacterium sp. Lactic acid bacteria, Lactobacillus sp. Lactic acid bacteria, Propionibacterium sp. Propionic acid bacteria, Clostridium butyricum (Clostridium butyricum) Butyric acid bacteria, Eubacterium
sp.) butyric acid-producing bacteria, such as trehalulose, palatinose, palatinose oligosaccharide, fructooligosaccharide, glucosyl sucrose, lactosucrose, theandelose, galactosyl lactose, lactulose, α-linked galactooligosaccharide, isomaltoligosaccharide, cyclodextrin, Branched cyclodextrins, trehalose, nigerooligosaccharides, panose, malto-oligosaccharides, gentigo-oligosaccharides, xylo-oligosaccharides, chitin oligosaccharides, chitosan oligosaccharides, soybean oligosaccharides, raffinose, beet oligosaccharides, indigestible dextrin, starch, cellulose, hemicellulose, glucan , Lignin, chitin, mannan, xylan, pectin, inulin, agar, guar gum, xanthan gum, gluconic acid, etc. Scan whey fermentation product as component, 2-amino-3-carboxy-1,4-naphthoquinone, 1,4-dihydroxy-2-naphthoic acid, myelin acids, and the like their degradation products. These components can be used alone or in combination of two or more.

  In addition, the maintenance of antioxidant capacity in the present invention refers to circulatory tissues and components such as blood vessels, serum, blood cells, etc. by ingesting ingredients containing one or more of vitamins, carotenoids, minerals or antioxidant food ingredients. In addition to improving the antioxidant environment for active enzymes and improving the antioxidant capacity of the living body, which has declined due to aging and lifestyle (stress, environmental pollution, lack of exercise, etc.), digestion, absorption, circulation, metabolism or immune It means that functional promotion occurs. In addition, when ingesting a composition for improving antioxidant capacity, it is necessary to consider active enzyme species, in vivo sites, and in vitro elimination chain reactions.

  Ingredients for improving antioxidant capacity of the present invention include vitamin A, vitamin B, vitamin C, vitamin E, tocotrienol, α-carotene, β-carotene, γ-carotene, lycopene, lutein, astaxanthin, zeaxanthin, tunaxanthin , Fucoxanthin, canthaxanthin, cryptoxanthin, ubiquinone, ubiquinol, copper, manganese, selenium, zinc, chromium, molybdenum, polyphenols, chlorophylls, bromophenol, thiol compounds, glutathione, cysteine, cysteine-containing peptides, BHT, BHA, Examples include sesaminol, terpenes, mucopolysaccharides and antioxidant enzymes. These components can be used alone or in combination of two or more.

The function enhancing composition and method for general foods, health functional foods or health supplements according to the present invention, such as digestion, absorption, circulation, metabolism, etc., decreased due to aging and lifestyle habits (stress, environmental pollution, lack of exercise, etc.) By improving the intestinal environment and antioxidant capacity, it is possible to improve the bioavailability of nutrients and functional ingredients of those foods. Therefore, if you try to have a well-balanced diet or supplement nutrients and functional ingredients with health functional foods or health supplements, it is difficult to achieve the expected effects. It is a very useful method for improving the effect expression by preparing for the improvement of utilization efficiency.

  Intestinal environment maintenance is realized by promoting the growth of useful bacteria such as bifidobacteria. By ingesting 0.5 to 10 g / day of fructooligosaccharide, which is a typical food ingredient, the bifidobacteria proliferate and become organic acids. Is generated. As a result, absorption of minerals and the like is promoted in the large intestine, and at the same time, as shown in Example 1 below, the ingestion of fructooligosaccharides maintains or improves the soundness of the small intestinal mucosa and increases the surface area, that is, the absorption surface. As a result, the absorption of nutrients and functional components is maintained or promoted. Examples of such universal absorption promotion include the promotion of anthocyanin absorption by ingestion of fructooligosaccharide in Example 2 below. Such an absorption promoting effect is confirmed by an increase in blood concentration or urinary excretion, or expected function enhancement such as visual improvement.

Next, the antioxidant capacity maintenance, reactive oxygen species (singlet oxygen ¹ O _2, superoxide O · ₂ ^-, hydrogen peroxide H ₂ O _2, hydroxyl radical OH ·, such lipid peroxides), in vivo site ( By taking into account the skin exposed to ultraviolet rays, blood vessels by lipid peroxide, liver, etc.) and in vitro elimination chain reactions (such as vitamin C returning vitamin E radicals resulting from inhibiting lipid oxidation). Both improvement of oxidative stress state and improvement of ability to prevent oxidative stress in the body (antioxidation preparation amount) are achieved. As a result, improvement in blood cell membrane plasticity, vascular flexibility, prevention and improvement of vascular narrowing, etc., and maintenance or improvement of the soundness of a nutrient or functional ingredient carrier such as LDL are achieved.

  In the intake of a component that performs antioxidative capacity maintenance, it is not necessary to limit the intake amount in particular, and the intake amount can be appropriately changed in the daily intake amount. The daily intake of the main antioxidant component is, for example, α-carotene 0.1-100 mg / day, β-carotene 0.5-200 mg / day, lycopene 0.1-100 mg / day, Vitamin E 10-1000 mg / day, tocotrienol 0.5-500 mg / day, vitamin C 50-2000 mg / day and glutathione 1-500 mg / day. Antioxidant capacity maintenance is obtained by ingesting a composition containing one or more of these components. As an example of such universal circulation / metabolism promotion, Example 3 described below includes an enhancement (synergistic) effect on the anti-surgery effect of the saden peptide by ingestion of vitamin E. Such an effect is confirmed by expected function enhancement such as a change in blood concentration or urinary excretion, or a decrease in blood pressure.

  Examples of the composition comprising a component for improving the intestinal environment for improving the in-vivo efficiency of general foods, health functional foods or health supplements and enhancing the functions of those foods and a component for improving antioxidant capacity include, for example, intestinal There are fructooligosaccharides that maintain the internal environment, and vitamin C, glutathione, α-carotene, β-carotene, lycopene, vitamin E, and tocotrienol as components that maintain antioxidant capacity. The number of bifidobacteria in the intestine increases as maintenance, and synergistic effects can be expected by reducing lipid peroxide, maintaining and improving the soundness of circulation, and increasing IgA in saliva. As an example of such a universal function enhancement, the situation of intestinal environment maintenance and antioxidant capacity maintenance in humans when ingesting the intestinal environment maintenance component and the antioxidant capacity maintenance component in combination in Example 4 below is shown. It is confirmed that preparations for improving the bioavailability of active ingredients of general foods, health functional foods or health supplements are made.

  The composition of the present invention may be mixed with other additives as necessary. These mixed powders can also be granulated. Any granulation method may be used as long as it is a known formulation technique. Therefore, it can also be made into granules using wet granulation methods such as stirring granulation, fluidized bed granulation and extrusion granulation, and other dry granulation methods. Moreover, these mixed powders or granules can also be produced into tablets or capsules. Furthermore, the liquid component can be mixed with other additives as required to make a powder. It can be granulated in the same manner as described above to form granules, tablets and capsules. The liquid component may be used in a liquid state, but other additives may be added as necessary to form a soft capsule.

  As a specific formulation example, fructooligosaccharides that are not oil-based components 1 g / day (for example, Mayoli P powder (Meiji Seika Co., Ltd.)), vitamin C 500 mg / day (for example, food additive ascorbic acid: manufactured by Roche), Glutathione 10 mg / day (for example, glutathione-containing yeast extract (manufactured by Kyowa High Foods Co., Ltd.)) is granulated with lactose, starch, dextrin, and pullulan as a base material. You can also Next, α-carotene 1.5 mg / day (for example, palm extract (manufactured by Lion Corporation)) and β-carotene 6 mg / day (for example, food additive β-carotene (San-Eigen FFI shares), which are fat and oil components, Lycopene 5 mg / day (for example, tomato extract (manufactured by Kyowa Hakko Kogyo Co., Ltd.)), vitamin E 134 mg / day (for example, food additive vitamin E (manufactured by Riken Vitamin Co., Ltd.)), tocotrienol 5 mg / day (For example, a palm extract (manufactured by Fuji Chemical Industry Co., Ltd.)) can be provided by combining a combination of two types of preparations using a vegetable oil and fat, an emulsifier as a base material and a gelatin as a film. As a feature of these preparations, it is possible to give a compact design that is easy to ingest compared with the case where the whole amount is made into granules or capsules. Moreover, the point that stabilization of the component in a formulation is aimed at because an aqueous component and an oil-based component do not contact is also mentioned.

Animal experiment in which human injuries of small intestinal mucosa are suppressed by ingestion of fructo-oligosaccharides 6-week-old NC / Jic male mice (25 to 30 g body weight) were preliminarily raised for 1 week in a standard chow diet (MF: Oriental Yeast Co., Ltd.) Then, it divided into 3 groups of A, B, and C group so that variation in body weight might not arise, and it used for the test as 7-10 animals per group. As shown in Table 1, AIN-93G feed was used as a basic composition, and fructooligosaccharides (Mayoligo P: manufactured by Meiji Seika Co., Ltd.) were replaced with sucrose, 0 (A group), 5 (Group B), 0 ( C group) A test feed containing% was prepared and allowed to freely ingest for 3 days for each group of 3 groups of mice. Artificial injury to the small intestinal mucosa using immunization with OVA (ovalbumin) was used as a model for reduced absorption due to aging and lifestyle. The group C was set as a normal group so as not to cause artificial injury to the small intestinal mucosa. On the seventh day after feeding, OVA was sensitized to abdominal cavity together with alum (Pierce Chemical Co.), and two weeks later, the same sensitization was performed. Two weeks after the second sensitization, OVA was orally administered, and after 3 hours, the jejunum was excised. A pathological section was prepared according to a conventional method, and the pathological image of the intestinal tract was observed by Hematoxilin-Eosin staining.

  As a result, as shown in FIG. 1, in the small intestine after ingestion of OVA in the OVA sensitized group, pathological images (center of FIG. 1) such as chorioedema and goblet cell increase are observed, whereas fructooligosaccharides are preliminarily observed. After the OVA ingestion of the OVA-sensitized group ingesting the above, the pathological condition was reduced, and the pathological image (right side of FIG. 1) was close to that of the normal group (left side of FIG. 1). Therefore, it was confirmed that the surface area of the small intestinal mucosa, which is the absorption surface, is secured by ingesting fructooligosaccharides.

Effects of promoting anthocyanin absorption by ingestion of fructooligosaccharides 7-week-old male Sprague-Dawley rats (body weight 250-300 g) were preliminarily raised on a standard solid diet (product name: MF, manufactured by Oriental Yeast Co., Ltd.) for 1 week, It was divided into 3 groups of A, B, and C groups so as not to cause variation, and 6 mice per group were used for the test. As shown in Table 2, using AIN-93G feed as a basic composition, fructooligosaccharide (Mayoligo P: manufactured by Meiji Seika Co., Ltd.) is replaced with sucrose, 0% (Group A), 2.5% (Group B), respectively. ), 5.0% (Group C) containing test feed was prepared and allowed to freely ingest for 3 days in each of the three groups of rats. On the 11th day after ingestion of the test feed, the rats were fasted for 8 hours under ether anesthesia, and a urine-collecting tube was attached to the penis of the rat and fixed to a ball man cage (KN: manufactured by Natsume Seisakusho). After recovery from anesthesia, an anthocyanin-rich cassis extract (Meiji cassis polyphenol: manufactured by Meiji Seika Co., Ltd.) dissolved in deionized water was orally administered through a stomach tube (50 mg / kg body weight / 10 ml as anthocyanin). Total urine excreted up to 18 hours after administration was collected in ice in a urine collection container to which 2.5 ml of 0.4 mol / L hydrochloric acid had been added in advance. After measurement of urine volume, the amount of anthocyanin contained in urine was measured by LC-MS. The amount of anthocyanin was defined as the sum of delphinidin-3-glucoside, delphinidin-3-lutinoside, cyanidin-3-glucoside, and cyanidin-3-lutinoside contained in BCA, and the urinary excretion rate relative to the anthocyanin dose was calculated.

  As shown in FIG. 2, the results show that both groups B and C ingested feed containing 2.5% and 5.0% fructooligosaccharides compared to group A without fructooligosaccharide intake. Since the excretion rate of middle anthocyanin increased significantly, fructooligosaccharides confirmed the effect of promoting anthocyanin absorption.

Effect of vitamin E intake to increase the antihypertensive effect of the sadden peptide 8 weeks old spontaneously hypertensive rat (SHR, male ) was pre-bred for 3 weeks with a standard chow diet (product name: MF, manufactured by Oriental Yeast Co., Ltd.), and then contracted Those having a blood pressure of 170 mmHg or more were used for the test. 42 SHR (body weight 240-310 g) were divided into 6 groups of A, B, C, D, E, and F groups so that blood pressure and body weight were averaged in each group, and 7 mice per group were used for the test. . Subsequently, d-α-tocopherol (manufactured by Tama Seikagaku Co., Ltd.) 0 mg / kg (Group A, Group D), 32 mg / kg (Group B, Group E), 160 mg / kg while freely taking the standard solid feed. (Group C, Group F) was diluted with olive oil so that it would become (Group C, Group F), and was orally administered continuously for 6 weeks, and body weight, blood pressure and heart rate were measured every week. In addition, in the 4th week after oral administration of d-α-tocopherol, the amount of saden peptide (containing valyltyrosine 0.1%: manufactured by Semen Extract Co., Ltd.) is 100 mg / kg (Group D, Group E, Group F). Were administered orally once to give a volume of 5 ml / kg (Group A, Group B, and Group C were administered with the same volume of a 0.5% carboxymethylcellulose aqueous solution), and changes in blood pressure and heart rate were measured. The results shown in FIGS. 3 to 7 below are expressed as mean values and standard deviations. For the significance test immediately before administration, Dunnet-type multiple comparison using error variance by the randomized block method, and controls in groups A, B and C The significant difference test for was performed by Student's t-test. Those with a significant difference of less than 5% and less than 1% are indicated by ** and *, and ## and #.

Continuous administration of d-α-tocopherol (change in systolic blood pressure (SBP) for 6 weeks after administration: FIG. 3, SBP transition for 8 hours after administration: FIG. 4) and single administration of saden peptide (d-α-tocopherol not administered) SBP transition 8 hours after administration of the saden peptide in the ward: FIG. 5), when compared with the presence or absence of each administration, the antihypertensive effect due to administration was observed while being small. On the other hand, in the SBP transition 8 hours after administration of the saden peptide in the d-α-tocopherol continuous administration group, as shown in FIG. 6 and FIG. Was synergistically recognized. Therefore, it was confirmed that the action of functional food materials is promoted by the maintenance of the antioxidant ability of vitamin E.

Intake test of composition for maintaining intestinal environment and antioxidant capacity As daily intake, 1 g of fructooligosaccharide (Mayoligo P powder: manufactured by Meiji Seika Co., Ltd.), vitamin C 500 mg (food additive ascorbic acid) : Roche) and glutathione 10 mg (glutathione-containing yeast extract: manufactured by Kyowa High Foods Co., Ltd.) were added to each base material of lactose, starch, dextrin and pullulan to form granules. Further, α-carotene 1.5 mg (palm extract: manufactured by Lion Corporation), β-carotene 6 mg (food additive β-carotene: manufactured by Saneigen FFI Corporation), lycopene 5 mg (tomato extract), which are oil-based components : Kyowa Hakko Kogyo Co., Ltd.), Vitamin E 134 mg (Food Additive Vitamin E: Riken Vitamin Co., Ltd.) and Tocotrienol 5 mg (Palm Extract: Fuji Chemical Industry Co., Ltd.) added with vegetable oil and emulsifier base material Soft capsules were formed by gelatin coating. Using these preparations, human clinical trials were conducted by double-blind crossover placebo comparison. The placebo was prepared by substituting the water-based component with dextrin and the oil-and-fat component with medium chain fatty acid so as not to be affected by the amount of sugar, lipid or mineral.

  In the test, 14 healthy subjects were divided into two groups, each taking a test preparation or a placebo for 28 days and then resting for 28 days. Next, the above two types of preparations were crossed over and ingested for 28 days. In addition, we refrained from taking supplements during the study period, and did not strictly restrict food. The results of the measurement items are shown in Table 3 as the status of intestinal environment maintenance and antioxidant capacity maintenance before and after taking the test preparation and placebo.

As a result, the ingestion of the test preparation improved the intestinal environment and antioxidant capacity, and maintained or promoted the absorption of nutrients and functional ingredients. Furthermore, improvement of blood cell membrane plasticity, vascular flexibility, prevention and improvement of vascular narrowing, etc., and maintenance or improvement of the health of nutrients such as LDL or carriers of functional ingredients were confirmed. As a result, the function of each food was enhanced by improving the in vivo utilization efficiency of various active ingredients of general foods, health functional foods or health supplements.

It is a figure which shows the influence of FOS (fructooligosaccharide) ingestion with respect to the intestinal injury induced by OVA (ovalbumin) sensitization. It is a figure which shows evaluation of the urinary excretion amount of anthocyanin by the anthocyanin absorption rate by fructooligosaccharide intake. It is a figure which shows evaluation of the hypotensive effect by continuous administration of d- (alpha) -tocopherol. It is a figure which shows evaluation of the hypotensive effect by single administration of d- (alpha) -tocopherol. It is a figure which shows evaluation of the synergistic effect of the saden peptide hypotensive effect by the d- (alpha) -tocopherol non-administration group. It is a figure which shows evaluation of the synergistic effect of the sadden peptide hypotensive effect by the administration group of d- (alpha) -tocopherol 32 mg / kg. It is a figure which shows evaluation of the synergistic effect of the saden peptide hypotensive effect by the administration group of d- (alpha) -tocopherol 160 mg / kg.

Claims (2)

An anthocyanin absorption promoter comprising a fructooligosaccharide as an active ingredient. The anthocyanin absorption promoter according to claim 1 , wherein the anthocyanin is an anthocyanin derived from cassis.

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