JP7465551B2 - NK cell activation composition - Google Patents

Description

The present invention relates to a composition that activates natural killer cells (NK cells).

Honey is not only edible, but is also known to have various health and beauty benefits. For example, honey can be used for various purposes, such as as an antibacterial agent (Patent Document 1), a wound treatment composition, and a cosmetic composition (Patent Documents 2 and 3).

On the other hand, NK cells are a type of cytotoxic lymphocyte that act as a key factor in natural immunity, and play a particularly important role in rejecting tumor cells and virus-infected cells. Due to their morphological characteristics, they are also called large granular lymphocytes. It is expected that activating NK cells can enhance immunity.

WO2016/072377 JP 2003-516357 A JP 2003-63984 A

The present invention aims to provide additional health benefits of honey.

As a result of intensive research conducted by the inventors to achieve the above-mentioned objective, they discovered the novel effect of honey in activating NK cells, which led to the completion of the present invention.

That is, the present invention relates to, for example, the following inventions.
[1]
A composition for activating natural killer cells comprising an effective amount of honey.
[2]
The composition of [1], wherein the honey is at least one selected from the group consisting of manuka honey, wildflower honey, and honeydew honey.
[3]
The composition of [1] or [2], which is a food composition or a pharmaceutical composition.

According to the present invention, it is possible to improve NK cell activation, which is expected to improve immunity.

1 is a graph showing the results of NK cell activity in Example 1.

The composition of the present invention contains honey as an active ingredient, an effective amount of honey, and is a composition that activates natural killer cells.

Honey is produced by bees using nectar collected from plant nectar, tree sap, and secretions from insects that parasitize plants as the main ingredient. In this embodiment, there are no particular limitations on the type of honey, and examples that can be used include manuka honey, honeydew honey, flower honey, acacia honey, clover honey, orange honey, astragalus honey, rosemary honey, sunflower honey, rapeseed honey, coffee honey, linden honey, coriander honey, horse chestnut honey, buckwheat honey, horse mackerel honey, Japanese laurel honey, Japanese black mochi honey, and Japanese pepper honey. It is preferable that the honey is selected from the group consisting of manuka honey, flower honey, and honeydew honey.

Honey may be used alone or in combination of two or more types. There are no particular limitations on the type of bee used to collect honey, or on the place of origin of the honey. There are no particular limitations on the place of origin of the honey, but manuka honey may be from New Zealand, for example, and honeydew honey may be from Bulgaria, for example. Honey may be used alone or in combination of two or more types.

Manuka (Leptospermum scoparium) is a woody plant of the Myrtaceae family that grows mainly in New Zealand. Among honeys, honey derived from Manuka is known to have particularly high antibacterial properties (JP Patent Publication No. 2007-277210).

Honeydew honey, known as "forest honey" in Europe, is made when insects first ingest the sap from various trees (oak, pine, fir, spruce, etc.), which is then removed by honeybees who then collect the sugars that remain in the form of water droplets on the leaves and trunks of the trees and turn them into honey. Like manuka honey, it is known to have strong antibacterial properties (Patent Publication No. 2018-119007).

Multifloral honey is not "monofloral honey" made from the nectar of one type of flower, but honey made from a variety of trees and wildflowers.

The type of bee used to collect honey is not particularly limited. Honey can be obtained, for example, as a beekeeping product in accordance with conventional methods.

While honey is stored in a beehive, it is generally kept at around 35°C by the body temperature of the bees. Honey collected from the beehive is generally heated as needed to reduce the viscosity and make transportation, packing, and other operations easier, and to melt any crystals.

After harvesting, the honey may be left as it is, or before or after heating, it may be subjected to purification processes such as removal of proteins, wax, debris, beehive residues, filtration, extraction with organic solvents, fractionation, sterilization, concentration, etc.

Honey is roughly 80% carbohydrate, with other healthy components such as vitamins, minerals, flavonoids, organic acids, and fatty acids, and the remainder being water. Most of the carbohydrates in honey are glucose and fructose, with small amounts of oligosaccharides and maltose also included.

In this embodiment, the content (effective amount) of honey in the composition may be, for example, 0.1% by weight or more, 1% by weight or more, 3% by weight or more, 5% by weight or more, 7% by weight or more, 10% by weight or more, 15% by weight or more, 20% by weight or more, 25% by weight or more, 30% by weight or more, 35% by weight or more, 40% by weight or more, 45% by weight or more, 50% by weight or more, 55% by weight or more, 60% by weight or more, 65% by weight or more, 70% by weight or more, 75% by weight or more, 80% by weight or more, 85% by weight or more, 90% by weight or more, 95% by weight or more, 97% by weight or more, 98% by weight or more, 99% by weight or more, 99.5% by weight or more, or 100% by weight. The honey content in the composition may be, for example, 99.5% by weight or less, 99% by weight or less, 98% by weight or less, 97% by weight or less, 95% by weight or less, 90% by weight or less, 85% by weight or less, 80% by weight or less, 75% by weight or less, 70% by weight or less, 65% by weight or less, 60% by weight or less, 55% by weight or less, 50% by weight or less, 45% by weight or less, 40% by weight or less, 35% by weight or less, 30% by weight or less, 25% by weight or less, 20% by weight or less, 15% by weight or less, 10% by weight or less, 7% by weight or less, 5% by weight or less, 3% by weight or less, 2% by weight or less, or 1% by weight or less.

The composition may further contain other known ingredients other than honey that have the ability to activate NK cells. Other ingredients that have the ability to activate NK cells include ingestible ingredients such as agaricus (β-glucan) and R-1 lactic acid bacteria.

The NK cell activation ability can be evaluated by using peripheral blood mononuclear cells (PBMCs) separated and collected from human whole blood and measuring the amount of free Eu ³⁺ after addition of a test substance by time-resolved fluorescence method.

The composition according to this embodiment may be a food composition, a pharmaceutical composition (drug), or a quasi-drug. In addition, honey may be used as a food composition (food) as it is, or may be added to food.

It is preferable that the food composition (food) is one in which the tertiary function of the food (function to regulate physical condition) is emphasized. Examples of foods in which the tertiary function of the food is emphasized include health foods, functional foods, nutritional compositions, dietary supplements, supplements, health foods, foods for specified health uses, foods with nutrient functions, and foods with functional claims.

When used as an additive to food, the food may contain ingredients that are acceptable for use in food. Examples of ingredients that are acceptable for use in food include minerals, vitamins, flavonoids, quinones, polyphenols, amino acids, nucleic acids, essential fatty acids, cooling agents, binders, sweeteners, disintegrants, lubricants, colorants, flavorings, stabilizers, preservatives, sustained-release regulators, surfactants, solubilizers, and humectants.

Foods that can be used for the above-mentioned purposes include the following, and an effective amount of honey can be mixed with intermediate products in the manufacturing process or with the final products to obtain foods for the above-mentioned purposes: beverages such as soft drinks such as coffee, juice, and tea drinks, milk drinks, lactic acid bacteria drinks, yogurt drinks, carbonated drinks, and alcoholic beverages such as sake, Western liquor, fruit wine, and honey wine; spreads such as custard cream; pastes such as fruit paste; Western confectioneries such as chocolate, donuts, pies, cream puffs, gum, jelly, candy, cookies, cakes, and puddings; Japanese confectioneries such as daifuku, mochi, manju, castella, anmitsu, and yokan; frozen desserts such as ice cream, popsicles, and sorbet; cooked foods such as curry, beef bowl, porridge, miso soup, soup, meat sauce, pasta, pickles, and jam; and seasonings such as dressings, furikake, umami seasonings, and soup bases.

The method for producing the food composition is not particularly limited, and any known method can be used as appropriate. For example, the food composition for the above purpose can be obtained by mixing the above honey with an intermediate product or a final product in the manufacturing process of the food composition.

The pharmaceutical or quasi-drug product may be in any form, such as a solid, liquid, or paste, and may be in the form of a tablet (including plain tablets, sugar-coated tablets, effervescent tablets, film-coated tablets, chewable tablets, troches, etc.), capsule, pill, powder (dispersed medicine), fine granules, granules, liquid, suspension, emulsion, syrup, paste, or injection (including the case where it is mixed with distilled water or an infusion such as an amino acid infusion or an electrolyte infusion at the time of use to prepare it as a liquid). These various preparations can be prepared, for example, by mixing the above-mentioned fermented product, which is the active ingredient, with other ingredients as necessary, and molding the mixture into the above-mentioned dosage form.

For example, examples include pharma- ceutically acceptable additives (such as excipients, binders, lubricants, disintegrants, emulsifiers, surfactants, bases, solubilizers, suspending agents, etc.), and food acceptable ingredients (such as minerals, vitamins, flavonoids, quinones, polyphenols, amino acids, nucleic acids, essential fatty acids, cooling agents, binders, sweeteners, disintegrants, lubricants, colorants, flavors, stabilizers, preservatives, sustained-release regulators, surfactants, solubilizers, and wetting agents).

The daily intake amount of honey contained in the composition according to this embodiment may be 0.01 to 70 g/day, and more preferably 4 to 70 g/day. The composition according to this embodiment may be taken once a day, or in multiple divided doses, such as twice or three times a day. There are also no particular limitations on the timing of intake, and it may be taken before or after meals, between meals, or before going to bed.

The present invention will be described in more detail below with reference to examples. However, the present invention is not limited to the following examples.

(Example 1) Examination of NK cell activation ability by various honeys
Twenty subjects were recruited and blood was collected. PBMCs were isolated from the whole blood of the subjects within 24 hours after blood collection. Test substances were suspended in culture medium, added to the PBMCs, and cultured. PBMCs cultured for 20 hours were used as effector cells, and human cancer cells (K562) labeled with a fluorescent substance (Eu ³⁺ ) were used as target cells, and the effector cells/target cells were mixed at a ratio of 40:1 and 20:1. After culturing the mixture for 4 hours, the amount of Eu ³⁺ released in the supernatant was measured by time-resolved fluorescence. The results are shown in Figure 1.

According to Figure 1, when honey was suspended in the medium at a final concentration of 0.8 μg/mL, and the E/T ratio was 20:1, the NK activity was 116% in manuka honey, 122% in mycelium honey, and 137% in honeydew honey compared to when no honey was added.

Claims (2)

A composition for activating natural killer cells, comprising an effective amount of at least one honey selected from the group consisting of manuka honey, wildflower honey and honeydew honey . The composition according to claim 1 which is a food composition or a pharmaceutical composition.

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