Nitric oxide production promoter and its use

Abstract

To develop a novel, safe and stable material for promoting NO (nitric oxide) production and provide a composition that allows the material to be effectively utilized for industrial purposes.SOLUTION: The present disclosure provides an NO production promoter for promoting NO production in a vascular endothelial cell, containing extract from leaves of Manuka (Leptospermum, Myrtaceae) as an active ingredient; and an oral composition such as food and drink, containing the NO production promoter.SELECTED DRAWING: None

Description

Technical Field

[0001] The present invention relates to a nitric oxide (NO) production promoter using a specific plant as a raw material and its use. More specifically, the present invention relates to a promoter for promoting NO production in vascular endothelial cells, which is characterized by containing an extract of the leaves of Manuka belonging to the genus Leptospermum of the Myrtaceae family as an active ingredient, and an oral composition for improving vascular endothelial function, which is characterized by containing the agent.

Background Art

[0002] It is known that vascular endothelium affects various functions such as vasodilation and / or vasoconstriction, proliferation and / or anti-proliferation of vascular smooth muscle cells, blood coagulation and / or anticoagulation, vascular inflammation and / or anti-inflammation, oxidation and / or anti-oxidation. Therefore, a decrease in vascular endothelial function is considered to be a cause of diabetes, hyperlipidemia, hypertension, obesity, etc., and is regarded as an early symptom of arteriosclerosis. Furthermore, since a decrease in vascular endothelial function is also caused by lack of exercise, excessive salt intake, smoking, etc., it is important to maintain and improve vascular endothelial function in daily life.

[0003] NO is produced from arginine by nitric oxide synthase (NOS). There are three different isoforms of NOS: neuronal nitric oxide synthase (nNOS), inducible nitric oxide synthase (iNOS), and endothelial nitric oxide synthase (eNOS) (Non-Patent Document 1). nNOS is a calcium-dependent enzyme and is involved in the regulation of synaptic plasticity in the brain. iNOS is a calcium-independent enzyme and is strongly induced by inflammation and stress and is mainly involved in immune function. Excessive NO production by iNOS causes sepsis and rheumatoid arthritis. eNOS is a calcium-dependent enzyme and is involved in vasodilation and suppression of thrombosis.

[0004] A decrease in NO production in vascular endothelial cells has been reported to suppress energy consumption in skeletal muscle and induce the progression of obesity and diabetes (Non-Patent Document 2). Actions of NO other than vasodilation include suppression of the binding of monocytes / macrophages to the vascular wall, antiplatelet aggregation action, and suppression of thrombus formation by inhibition of platelet adhesion / aggregation. Other vasodilatory factors released from vascular endothelial cells include endothelium-derived hyperpolarizing factor, prostaglandin I2, etc., and it has been clarified that various bioactive substances such as endothelin, thromboxane A2, and angiotensin II are produced and secreted as vasoconstrictive factors. The balance of these factors regulates and maintains vascular function.

[0005] Regarding manuka described below, the following is known. That is, manuka is a medicinal tree that has been cherished by the indigenous Maori people of New Zealand since ancient times, and its seeds, bark, leaves, etc. have been used in various ways as crude drugs (Non-Patent Document 3). Also, manuka honey collected from the nectar of manuka flowers contains methylglyoxal and has been reported to have antibacterial action (Non-Patent Document 4). In addition, a therapeutic agent for periodontitis (Patent Document 1) has been proposed. However, no finding has been found that oral ingestion of the components contained in manuka leaves promotes NO production in vascular endothelial cells.

Prior Art Documents

Patent Documents

[0006]

Patent Document 1

Non-Patent Documents

[0007]

Non-Patent Document 1

Non-Patent Document 2

[0008] In view of such a situation, an object of the present invention is to develop a safe and stable novel material for promoting NO production in vascular endothelial cells, and to provide a composition in a form that can be effectively utilized industrially. [Means for Solving the Problems]

[0009] To solve the above problems, the present inventors have intensively studied materials for promoting NO production in vascular endothelial cells. As a result, unexpectedly, Manuka leaves are extremely effective, and these plants contain components that can significantly promote NO production in humans and animals. The combined use of these components can more significantly promote NO production in vascular endothelial cells. Furthermore, it has been found that these can be effectively utilized in fields such as food and drink products, pharmaceuticals, quasi - drugs, and feeds, thus completing the present invention.

[0010] That is, according to the present invention, there is provided a NO production promoter characterized by containing an extract of the leaves of Leptospermum scoparium belonging to the genus Leptospermum of the Myrtaceae family as an active ingredient. This aqueous component is preferably an extract obtained by subjecting the leaves of the above-mentioned manuka to an extraction treatment with water and / or a lower alcohol.

[0011] The extract obtained by the treatment as described above is a complex composition containing a wide variety of components, although there are quantitative differences, and includes leptosperin, β-triketone, terpinen-4-ol, 1,8-cineole, pteridinedione, 3,6,7-trimethyl-lumazine, polyphenols, various water-soluble components (polysaccharides, oligosaccharides, monosaccharides, proteins, peptides, amino acids, complexes thereof, etc.).

[0012] The NO production promoter of the present invention is characterized by promoting NO production in vascular endothelial cells.

[0013] Another feature of the present invention lies in the provision of an oral composition containing the above-mentioned NO production promoter. The form of this oral composition is preferably a food or drink.

[0014] Furthermore, according to the present invention, there is provided an oral composition or a food or drink for anti-fatigue, characterized by containing the above-mentioned NO production promoter.

[0015] Yet another feature of the present invention lies in a method for producing a NO production promoter containing, as an active ingredient, an extract obtained by extracting the leaves of manuka belonging to the genus Leptospermum of the Myrtaceae family with water and / or a lower alcohol.

[0016] Still another feature of the present invention lies in a method of orally administering or ingesting the above-mentioned NO production promoter or oral composition in order to promote NO production in vascular endothelial cells.

Effects of the Invention

[0017] The extract of manuka leaves according to the present invention is excellent in quality stability, and by promoting NO production in vascular endothelial cells, it can prevent and / or improve symptoms caused by vascular function disorders such as Raynaud's disease, arteriosclerosis, Buerger's disease, hypertension, cerebral thrombosis, cerebral infarction, myocardial infarction, congestion, stasis, bleeding, anemia, dementia, decreased immunity, alopecia, malaise, fatigue, muscle pain, bloodshot eyes, swelling, stiff shoulders, low back pain, itching of the skin, dark circles, dullness, heat rash, frostbite, wrinkles, decreased skin elasticity, periodontal disease, etc., and has effects such as hair growth, hair nourishment, hair strengthening, nourishing and tonifying, and beautifying the skin. Such effects are significantly expressed by orally ingesting or administering a NO production promoter containing the processed product as an active ingredient. Therefore, according to the present invention, an oral composition containing an extract of manuka leaves as an active ingredient is provided, and this can be effectively used as foods and drinks, pharmaceuticals, quasi-drugs, feeds, etc. for preventing and / or improving various symptoms caused by a decrease in NO production in vascular endothelial cells.

Embodiments for Carrying Out the Invention

[0018] The present invention will be described in detail below. First, the NO production promoter of the present invention has a function of promoting NO production in vascular endothelial cells of humans and animals, and is characterized by containing an extract of the leaves of manuka (Leptospermum scoparium) belonging to the genus Leptospermum of the family Myrtaceae as an active ingredient.

[0019] The extract of the Manuka leaves can be produced by any method, but it is preferable to perform the extraction process using water and / or lower alcohols. As the carbon number of the lower alcohol increases, the tendency for oily substances in the defatted meal to be extracted becomes greater. Therefore, those with a carbon number of about 5 or less are desirable, and examples include methanol, ethanol, normal propanol, isopropanol, normal butanol, isobutanol, etc. When using a lower alcohol with a large carbon number, it is advisable to increase the moisture content to suppress the extraction of oily components in the defatted meal. For example, the moisture content in the case of n-propanol is about 20% by mass to about 50% by mass, and the moisture content in the case of n-butanol is about 40% by mass to about 70% by mass. Desirable extraction solvents are water, methanol, and ethanol, and their hydrous alcohols (moisture content: 0 to 100% by mass).

[0020] To extract the Manuka leaves, the extraction solvent is added in an amount of about 1 to about 30 times the mass of 1 part by mass of the Manuka leaves, and the mixture is stirred and mixed at normal pressure or under a pressure of 1 to 5 atmospheres, at room temperature or about 120 °C, for about 10 minutes to about 3 hours. Then, it is cooled to room temperature and filtered. The filtrate is concentrated and dried by appropriate means such as vacuum drying, spray drying, freeze drying, etc. The dried product may be appropriately pulverized. In this way, a pale yellow to yellowish-red solid, which is the extract of the Manuka leaves according to the present invention, can be obtained. It is desirable to repeat the extraction process on the extraction residue that has been once extracted, or to perform the extraction process under a pressure of 1 to 3 atmospheres at about 100 °C to about 130 °C. This increases the yield of the extract according to the present invention. This extract contains polyphenols, saponins, etc.

[0021] The NO production promoter of the present invention can be in the form of a solid, paste, or liquid with the extract as its active ingredient, and this can be used directly as the NO production promoter. However, if necessary, known additives used in the applications where the NO production promoter of the present invention is utilized can be used in combination and incorporated by conventional methods to prepare a composition. Here, the known additives are preferably those commonly used for oral intake. For example, additive substances such as excipients, binders, disintegrants, lubricants, wetting agents, fluidizing agents, preservatives, surfactants, stabilizers, diluents, solubilizers, isotonic agents, bactericides, antiseptics, flavoring agents, odor-correcting agents, coloring agents, and fragrances can be used, or known components having an NO production promoting effect and their containing materials can also be used in combination.

[0022] Known components and materials with the effect of promoting NO production in vascular endothelial cells include, in addition to the above, black vinegar, glutathione, ginkgo leaf extract, hesperidin, citrulline, rutin, ginger, black ginger, hihatsu, grape stem extract, grape peel extract, trans-resveratrol, apple peel extract, black soybean polyphenol, cocoa polyphenol, picnogenol, flavangenol, cinnamon, Korean ginseng, egg white peptide, collagen peptides derived from chicken, pig, or fish, camellia seed extract, acanthopanax root extract, etc. It should be noted that the present invention is not limited by these examples.

[0023] In the present invention, the aforementioned NO production promoter can be used as it is in various products in the food and beverage, pharmaceutical, quasi-drug, feed, and other industrial fields, or can also be used as part of the formulation raw materials of these various products. In particular, it is preferably made into an oral composition for promoting NO production, and the most suitable form of this oral composition is a food and beverage. Although an example is described below, the present invention is not limited thereby.

[0024] When the NO production promoter of the present invention is an oral composition, it can be made into oral preparations such as granules, tablets, capsules, and liquids. The content of the extract derived from the leaves of manuka in such a pharmaceutical composition is difficult to uniformly define depending on the type and content of the combined raw materials, etc., but generally it is about 0.001% by mass to about 90% by mass, more preferably about 0.01% by mass to about 70% by mass. When the content is less than about 0.001% by mass, the desired effect of the present invention cannot be recognized, and when it exceeds about 90% by mass, it becomes difficult to prepare a practical pharmaceutical composition. The NO production promoter of the present invention is preferably used in a mode of being orally ingested or administered. A suitable amount standard of the NO production promoter of the present invention in the case of oral ingestion or administration is about 10 mg to about 1,000 mg, preferably about 30 mg to about 500 mg, and more preferably about 50 mg to about 300 mg per day for an adult human based on the aqueous component or the extract contained in the agent.

[0025] The NO production promoter of the present invention can itself be made into products in various forms in the food and beverage industry, pharmaceuticals, feeds, and other industrial fields, or it can also be used in a mode of being a part of the blending raw materials of such products. As a practical use, food and beverage products are preferred.

[0026] Specific examples of food and beverage products include beverages such as vegetable juice, fruit juice drinks, soft drinks, tea, etc., instant noodles, soups, jellies, puddings, yogurt, cake mix products, confectioneries, furikake, miso, soy sauce, sauces, dressings, mayonnaise, vegetable creams, seasonings such as sauce for grilled meat and noodle soup, noodles, udon, soba, spaghetti, processed livestock and fish products such as ham and sausage, hamburgers, croquettes, furikake, tsukudani, jam, milk, cream, butter, powdered, solid or liquid dairy products such as spreads and cheeses, margarine, bread, cakes, cookies, chocolates, candies, gummies, gums, jellies, etc. In addition to various general processed foods, powdered, granular, pill-shaped, tablet-shaped, soft capsule-shaped, hard capsule-shaped, paste-shaped or liquid nutritional supplements, foods for specified health uses, foods with functional claims, health foods, thick liquid foods and therapeutic foods for patients with dysphagia can be mentioned.

[0027] In the food or drink of the present invention, it can be in a form with at least one indication that it contains an extract of manuka leaves as an active ingredient and that it is for promoting NO production in vascular endothelial cells.

[0028] To produce these foods and drinks, the NO production promoter of the present invention and known raw materials can be used, or a part of the known raw materials can be replaced with the above-mentioned NO production promoter, and they can be produced by conventional methods. For example, the NO production promoter of the present invention can be mixed with excipients such as glucose (dextrose), dextrin, lactose, starch or its processed products, cellulose powder, vitamins, minerals, oils and fats of animals, plants, and seafood, proteins (including proteins derived from animals, plants, and yeast and their hydrolysates, etc.), carbohydrates, pigments, flavors, antioxidants, surfactants, other food additives, and edible materials such as powders and extracts containing various nutritional and functional components, and then processed into shapes such as powders, granules, pellets, tablets, etc., or processed into general processed foods as in the above examples by conventional methods, or a liquid mixture of these can be coated with a coating agent such as gelatin, sodium alginate, carboxymethyl cellulose, etc. and formed into capsules, or processed into the form of beverages (drinks) and used as dietary supplements or health foods. In particular, tablets, capsules, and drinks are desirable.

[0029] The ratio of the NO production promoter of the present invention to be formulated in such foods and drinks is difficult to uniformly define due to differences in the form of the foods and drinks, the content of the above-mentioned extract (extract of manuka leaves) in the NO production promoter of the present invention, the types, components, and blending amounts of other blending raw materials, etc. However, the NO production promoter of the present invention can be appropriately combined with other known raw materials for food and drink production so that the content of the above-mentioned extract in the food and drink is about 0.01% by mass to about 90% by mass, more preferably about 1% by mass to about 50% by mass, and the target food and drink can be prepared according to conventional methods. The food and drink of the present invention can be taken into the body by any method, such as oral ingestion or tube feeding, simultaneously with or before or after a meal intake, with the daily intake guideline of the above-mentioned aqueous component for an adult human being being about 10 mg to about 1,000 mg, preferably about 30 mg to about 500 mg, and more preferably about 50 mg to about 300 mg.

[0030] The pharmaceutical using the NO production promoter of the present invention can be prepared by appropriately adding known excipients and additives that do not conflict with the gist of the present invention to the above-mentioned NO production promoter and processing it by a conventional method into preparations such as tablets, capsules, granules, powders, and liquids. It is administered orally or enterally and applied for promoting NO production or preventing or treating the above-mentioned various symptoms. The blending amount of the NO production promoter of the present invention is difficult to uniformly set depending on its form, the type, form, usage, and dosage of the above-mentioned pharmaceutical preparation, etc., but is generally 0.001% by mass to 50% by mass as the content of the above-mentioned extract. The intake amount in the case of oral administration is not particularly limited. For example, based on the above-mentioned extract, it is about 0.1 mg to about 1,000 mg, preferably about 1 mg to about 500 mg, and more preferably about 10 mg to about 300 mg per day for an adult human.

[0031] In addition, to apply the NO production promoter of the present invention to pet food or livestock feed, similar to the case of the above-mentioned food and drink, it can be blended with various known feeds and drinking water, or processed into preparations in the form of tablets, granules, capsules, etc. together with known raw materials and additives. In these cases, the blending amount and intake amount of the NO production promoter of the present invention are about 0.01% by mass to about 90% by mass, more preferably about 1% by mass to about 50% by mass as the content of the above-mentioned extract, and the standard of the intake amount per day is about 0.1 mg to about 100 mg, more preferably about 0.5 mg to about 50 mg per kg of the body weight (kg) of the applied animal based on the above-mentioned extract.

Example

[0032] Production Example 1 The dried leaves of New Zealand manuka (Leptospermum scoparium) were coarsely pulverized. 1 Kg of these dried manuka leaves was charged into a stainless steel extraction kettle, 9 L of water was added, and extraction treatment was carried out at 70 °C for 6 hours while stirring appropriately. Thereafter, the insoluble residue was filtered off to collect an extract solution, and the extract solution was subjected to reduced pressure concentration, freeze-drying, and pulverization treatment to obtain a brown extract powder (Sample M-1).

[0033] Production Example 2 To 100 g of the dried leaves obtained by the method described in Production Example 1, 250 mL of hydrous ethanol (water content 50%) was added, and the mixture was heated under reflux at 80°C for 1 hour. After cooling to room temperature, it was filtered to separate the filtrate. To this filtration residue, 200 mL of hydrous ethanol (water content 50%) was added again, and the mixture was heated in the same manner. After cooling, it was filtered to collect the filtrate. The two filtrates were combined and concentrated under reduced pressure, followed by freeze-drying and pulverization to obtain a brown extract powder (Sample M-2).

[0034] Production Example 3 1 kg of the dried leaves obtained by the method described in Production Example 1 was charged into a stainless steel extraction kettle, 9 L of ethanol was added, and the mixture was subjected to an extraction treatment at 70°C for 6 hours while stirring appropriately. Thereafter, the insoluble residue was filtered off to collect the extract solution, and the extract solution was subjected to concentration under reduced pressure, freeze-drying, and pulverization treatments to obtain a brown extract powder (Sample M-3).

[0035] Test Example The NO production promoting effect of each sample obtained in the above Production Example was examined by the method described below.

[0036] Test Example 1: NO production promoting effect of an extract derived from the leaves of manuka on bovine aortic endothelial cells (BAEC) To examine the NO production promoting effect in animal cells, BAEC was used. BAEC was seeded in a 96-well plate at 1×10 4 cells / well and cultured at 37°C for 1 day. Thereafter, DAF-FM DA, a fluorescent probe for NO detection, was incorporated into the cells, and Samples M-1, M-2, and M-3 were added at 10, 25, 50, and 100 μg / mL, followed by incubation at 37°C for 24 hours. After completion of the culture, the fluorescence intensity at an excitation wavelength of 490 nm and an emission wavelength of 520 nm was measured, and it was expressed as the mean value ± standard deviation (n = 3) as the relative value (activity) when the NO production amount in the case of no sample addition was taken as 1 (Table 1).

[0037] The results are shown in Table 1. From the data in the table, it was confirmed that the extract derived from the leaves of manuka according to the present invention has a NO production promoting effect on bovine aortic endothelial cells in a concentration-dependent manner.

[0038]

Table 1

[0039] Test Example 2: Promoting effect of an extract derived from Manuka leaves on NO production in human umbilical vein endothelial cells (HUVECs) To examine the promoting effect on NO production in human cells, HUVECs were used. HUVECs were seeded at 1×10 4 cells / well in a 96-well plate and cultured at 37°C for 1 day. Thereafter, DAF-FM DA, a fluorescent probe for NO detection, was incorporated into the cells, and Samples M-1, M-2, and M-3 were added at 10, 25, 50, and 100 μg / mL, followed by incubation at 37°C for 24 hours. After the culture, the fluorescence intensity at an excitation wavelength of 490 nm and an emission wavelength of 520 nm was measured, and it was expressed as the mean value ± standard deviation (n = 3) as the relative value (activity) when the NO production amount in the case of no sample addition was set to 1 (Table 2).

[0040] The results are shown in Table 2. From the data in the table, it was confirmed that the extract derived from Manuka leaves according to the present invention also has a concentration-dependent promoting effect on NO production in human umbilical vein endothelial cells.

[0041] [Table 2]

[0042] Test Example 3: Promoting effect of extracts derived from other plants on NO production in human umbilical vein endothelial cells (HUVECs) In this test, as NO production promoters for comparison with the extract derived from Manuka leaves of the present invention, Tie2 Hihatsu extract powder (Tie2 Hihatsu extract powder MF, manufactured by Maruzen Pharmaceutical Co., Ltd.) (referred to as Comparative Sample 1), blackcurrant polyphenols (Meiji Blackcurrant Polyphenols (AC10), manufactured by Meiji Food Materials Co., Ltd.) (referred to as Comparative Sample 2), and hesperidin (αG Hesperidin PA-T, manufactured by Toyo Seito Co., Ltd.) (referred to as Comparative Sample 3) were used. The measurement of the NO production amount was performed using the same method as in Test Example 2, and it was expressed as the mean value ± standard deviation (n = 3) as the relative value (activity) when the NO production amount in the case of no sample addition was set to 1 (Table 3).

[0043] The results are shown in Table 3. From the data in the table, it was confirmed that the extract derived from the leaves of manuka according to the present invention has a more remarkable NO production promoting effect than other NO production promoters in human umbilical vein endothelial cells.

[0044] [Table 3]

[0045] Test Example 4: NO production promotion test and anti-fatigue test in mice The NO production promoting effect and anti-fatigue effect were examined by the following method. That is, 6-week-old ddy male mice (Sankyo Labo Service Co., Ltd.) were pre-fed for 1 week, then divided into groups of 6 mice each, and divided into a control group administered with distilled water and a sample M-1 administration group. They were allowed to freely ingest a common feed (manufactured by Nippon Clea Co., Ltd., trade name CE-2), and 200 mg / kg body weight / day of each sample was orally administered daily. All mice were subjected to swimming exercise 3 times a week for 4 weeks. At the second week of breeding, a 2 g weight was attached to the tail of the mice, and they were made to swim in a water tank. The time (limiting swimming time) until the swimming exercise could no longer be continued, when the top of the mouse's head sank below the water surface due to fatigue and exhaustion, was measured. In addition, after the breeding was completed, the blood of the mice was collected, and NO in the plasma obtained by centrifugation was measured using a NO2 / NO3 Assay Kit-C II (Colorimetric) ~ Griess Reagent Kit ~ (manufactured by Dojindo Laboratories). The blood NO concentration was expressed as the relative value when the value of the control group was set to 100, as the average value ± standard deviation (Table 4).

[0046] The results are shown in Table 4. From the data in the table, it was confirmed that the extract derived from the leaves of manuka according to the present invention significantly increased the NO concentration in the blood and also significantly extended the limiting swimming time.

[0047] [Table 4]

[0048] Test Example 5: Anti-fatigue test in humans Twenty healthy men (aged 21 to 30 years, average age: 24.8 years) who exercised regularly and had given consent to participate in the test were divided into two groups of 10 each. Each group was given a gelatin capsule filled with 200 mg of placebo (maltodextrin) or sample M-1 once a day for 4 weeks. The subjects continued to exercise as usual in their daily lives, and a Visual Analog Scale (VAS) questionnaire ("Anti-Fatigue Clinical Evaluation Guidelines", Japanese Society of Fatigue Science, 2011) was conducted for the evaluation of fatigue. The data were expressed as mean ± standard deviation (Table 5).

[0049] The results are shown in Table 5. A lower VAS value indicates a reduction in fatigue. From the data in Table 5, it was revealed that the extract derived from the leaves of manuka according to the present invention can reduce the feeling of fatigue.

[0050]

Table 5

[0051] Prototype Example 1 Any one of samples M-1 to M-3 as the NO production promoter of the present invention was supplied to a capsule filling machine, and a gelatin-coated hard capsule preparation with a content volume of 200 mg per capsule was prototyped by a conventional method. These capsule preparations can be used as dietary supplements, pharmaceuticals, etc. that can be taken orally.

[0052] Prototype Example 2 Any one of samples M-1 to M-3: 150 parts (by mass; the same applies hereinafter) as the NO production promoter of the present invention, beeswax: 40 parts, and evening primrose oil (manufactured by Efamol, UK): 80 parts were heated and mixed at about 50 °C until homogeneous, and then supplied to a capsule filling machine to prototype a gelatin-coated soft capsule preparation with a content volume of 200 mg per capsule by a conventional method. These capsule preparations can be used as dietary supplements that can be taken orally.

[0053] Prototype Example 3 As a NO production promoter of the present invention, any one of Samples M-1 to M-3: 30 parts, green tea extract (manufactured by BHN Co., Ltd.): 0.5 part, corn starch (manufactured by Nippon Corn Starch Co., Ltd.): 105 parts, tricalcium phosphate (manufactured by Yoneyama Chemical Industry Co., Ltd.): 50 parts, and riboflavin (manufactured by DSM Nutrition Japan Co., Ltd.): 7 parts were charged into a mixer and stirred and mixed for 10 minutes. This mixture was fed into a direct compression tableting machine to produce tablets having a diameter of 7 mm, a height of 4 mm, and a mass of 150 mg / tablet. Then, a shellac coating was formed with a coating machine to prototype a tablet-shaped food product.

[0054] Prototype Example 4 To 100 mL of a commercially available nutritional drink, any one of Samples M-1 to M-3: 200 mg as a NO production promoter of the present invention was added and thoroughly mixed to prototype a beverage. No abnormalities or discomfort were observed in the appearance and flavor even after storing this in a refrigerator for 1 year. Incidentally, this product can be used for promoting NO production in vascular endothelial cells, improving endurance, and preventing fatigue.

[0055] Prototype Example 5 In the manufacturing process of instant noodles, any one of Samples M-1 to M-3: 300 mg as a NO production promoter of the present invention was added to known raw materials to prototype instant noodles. No abnormalities or discomfort were observed in the appearance and flavor even after storing this at room temperature for 6 months. Incidentally, this product can be used for promoting NO production in vascular endothelial cells, improving endurance, and preventing fatigue.

Industrial Applicability

[0056] The NO production promoter of the present invention, which contains an extract of the leaves of manuka belonging to the genus Leptospermum of the Myrtaceae family as an active ingredient, has the effect of promoting NO production in vascular endothelial cells by oral ingestion, and thus can be effectively used for foods and drinks, pharmaceuticals, quasi-drugs, feeds, etc. for improving symptoms caused by promotion of NO production and / or reduction of NO production in vascular endothelial cells.

Claims

1. 1. A NO (nitric oxide) production promoter, comprising as an active ingredient an aqueous component of an extract of the leaves of Manuka, which belongs to the genus Leptospermum of the Myrtaceae family.

2. 2. The method according to claim 1, wherein the extract is a water extract of manuka leaves. An NO production promoter.

3. The NO production promoter according to claim 1 or 2, which promotes NO production in vascular endothelial cells.

4. An oral composition comprising the NO production promoter according to any one of claims 1 to 3.

5. The oral composition according to claim 4, which is a food or drink.

6. 6. The oral composition according to claim 4 or 5, for improving endurance or preventing fatigue.

7. A method for producing an NO production promoter, which comprises incorporating an aqueous component of an extract of manuka leaves as an active ingredient.

8. A composition for improving endurance or a composition for preventing fatigue, comprising an NO production promoter obtained by the method according to claim 7.

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