Combination for improving atp production

Abstract

To provide a motility improver for male sperms by oral ingestion.SOLUTION: The orally ingested male sperm motility enhancing agent of the present invention contains nicotinamide mononucleotide (NMN), coenzyme Q10, and 5-aminolevulinic acid (5-ALA) as essential components. The agent for improving sperm motility can be used for infertility treatment of an adult male with reduced sperm motility and / or reduced sperm concentration, or for pregnancy activity (fertility) of an adult male. Another application is in the breeding of domesticated animals.SELECTED DRAWING: Figure 2

Description

[Technical Field]

[0001] The present invention provides A combination drug that improves ATP production Regarding. [Background technology]

[0002] Japan is facing a declining birthrate and an aging population, and the population decline is expected to continue. Countermeasures are attracting attention, with infertility treatment becoming eligible for insurance coverage in 2022. In recent years, understanding of male sperm has advanced, and infertility treatment is now required to address male infertility. Semen analysis has revealed that the number of men experiencing infertility due to decreased sperm concentration, decreased sperm motility, and an increased rate of abnormal sperm is on the rise.

[0003] Thus, there is an urgent need to establish new methods for improving sperm function, but there are few examples of sperm research, and the reality is that we are currently exploring the establishment of effective methods for improvement. [Prior art documents] [Patent documents]

[0004] [Patent Document 1] Japanese Patent Application Laid-Open No. 2016-37473 [Patent Document 2] Japanese Patent Application Publication No. 2018-172346 [Patent Document 3] International Publication No. 2022 / 054778 [Patent Document 4] International Publication No. 2009 / 139156 [Non-patent literature]

[0005] [Non-Patent Document 1] Domestic Journal Author (Hamada Takeyuki) Title of paper: "The effect of 5-aminolevulinic acid (ALA) on improving semen findings" Publication name (Journal of the Japanese Society for Reproductive Medicine) Publication year (2017) Vol.62, No.4 p.208, Abstract No.O-132 [Non-patent document 2] Wellness Life Science NMN25000 120 Capsules, Sofmap, search date: August 20, 2024 (Reference 1 of the original application) [Non-patent document 3] Dokimin NMN 5-ALA Astaxanthin PQQ Q10 30 tablets, Amazon, search date August 20, 2024 (reference 2 of the original application) [Non-patent document 4] Free Radical Biology and Medicine, 2016, 100(Supp. 1):S105-S106 (Reference 4 in the original application) Summary of the Invention [Problem to be solved by the invention]

[0006] The problem to be solved by the present invention is: A combination drug that can improve ATP production through the action of three essential components The purpose is to provide [Means for solving the problem]

[0007] The gist of the present invention is as follows. (1) The combination of the present invention for improving ATP production teeth, Contains three essential ingredients: nicotinamide mononucleotide (NMN), coenzyme Q10, and 5-aminolevulinic acid (5-ALA). It was made into a capsule formulation It is a combination drug So, The action of these three components improves ATP production It is characterized by: (2) The combination drug of the present invention for improving ATP production comprises: A combination drug in the form of a capsule containing three essential ingredients: nicotinamide mononucleotide (NMN), coenzyme Q10, and 5-aminolevulinic acid (5-ALA), The action of the three components improves ATP production and suppresses ROS production. . ( 3 ) The three components of nicotinamide mononucleotide (NMN), coenzyme Q10, and 5-aminolevulinic acid (5-ALA) of The content is in a mass ratio of 0.25-0.80:0.06-0.80:0.005-0.80. ( 4) any one of the nicotinamide mononucleotide (NMN), the coenzyme Q10, and the 5-aminolevulinic acid (5-ALA) teeth It is contained in the form of salts. [Effects of the Invention]

[0008] The present invention According to a combination drug that improves ATP production , The action of the three components shown in Figure 1, and As is clear from the results of the examples described below, , 2 Compared to using coenzyme Q10, 5-aminolevulinic acid (5-ALA) individually, ATP (Adenosine triphosphate) production Increases ROS (Reactive Oxygen Species) production It has been confirmed that it has an excellent effect in suppressing [Brief explanation of the drawings]

[0009] [Figure 1] FIG. 1 is an explanatory diagram regarding the action of a drug combination to improve ATP production according to an embodiment. [Figure 2] 1 is a graph showing the results of Test Example 1, which confirms the effect of a drug combination on improving ATP production. [Figure 3] 1 is a graph showing the results of Test Example 2 confirming the effect of a drug combination on improving ATP production. DETAILED DESCRIPTION OF THE INVENTION

[0010] Hereinafter, " A combination drug that improves ATP production However, the technical scope of the present invention is not limited to the following embodiments.

[0011] According to this embodiment A combination drug that improves ATP production is a combination drug containing three essential ingredients: nicotinamide mononucleotide (NMN), coenzyme Q10, and 5-aminolevulinic acid (5-ALA).

[0012] Nicotinamide mononucleotide (NMN) is, for example, represented by the following chemical formula: [ka] Coenzyme Q10 is, for example, represented by the following chemical formula: [ka] 5-aminolevulinic acid (5-ALA) is, for example, represented by the following chemical formula: [ka]

[0013] The relative ratios of nicotinamide mononucleotide (NMN), coenzyme Q10, and 5-aminolevulinic acid (5-ALA), when the total amount of the three components is taken as 1, are preferably set at a mass ratio of 0.25-0.80:0.06-0.80:0.005-0.80, for example. A ratio of 1:1:1 is more preferred. Nicotinamide mononucleotide (NMN), coenzyme Q10, and 5-aminolevulinic acid (5-ALA) are preferably contained in a form that can be represented by the above-mentioned chemical formula, but this is not limited thereto. For example, at least one component or all three components may be contained in the form of a derivative (i.e., a compound modified to a degree that does not significantly alter the parent structure or properties) or salt. Salts of the derivatives may also be included.

[0014] A combination drug that improves ATP production Preferably, the three components (nicotinamide mononucleotide (NMN), coenzyme Q10, and 5-aminolevulinic acid (5-ALA)) are blended by mixing or the like so that the total amount of the three components (including derivatives or salts) is 0.001% by mass to 100% by mass, preferably in the above ratios. Other components include compounds added as other functional components, additives used in tableting, solvents used in liquid formulations, and additives used to maintain stable storage conditions as a product.

[0015] Nicotinamide mononucleotide (NMN), coenzyme Q10, and 5-aminolevulinic acid (5-ALA) are already used as ingredients in supplements and the like, although their purposes and uses are different from those of this embodiment, and they are known to be safe for the human body when taken orally or parenterally (for example, by applying to the skin). This embodiment is novel in that it combines these three components from known compounds, and by combining them, it is possible to obtain a more effective effect than if they were taken individually. ATP production It is valuable to have found that this can provide an improvement effect (see the results of the Examples below for details).

[0016] A combination drug that improves ATP production The usage form of , economics It may be used as an oral or parenteral agent. Specific examples include tablets, powders, granules, dry syrups, capsules, liquids, and gels. 。

[0017] Here, referring to FIG. 1, A combination drug that improves ATP production Depending on Rusaku The following describes its use. Figure 1 shows the effects of each component, nicotinamide mononucleotide (NMN), coenzyme Q10, and 5-aminolevulinic acid (5-ALA), and also illustrates the organic synergistic effects of the three components combined. The mechanism is inferred from the results of the Examples described below. As shown in Figure 1, we speculate that the organic synergistic effects of the three-component combination of nicotinamide mononucleotide (NMN), coenzyme Q10, and 5-aminolevulinic acid (5-ALA) contribute to mitochondrial activity. More specifically, nicotinamide mononucleotide (NMN) produces NAD, which captures hydrogen ions in the TCA cycle, together with vitamin B3. Coenzyme Q10 moves freely within mitochondria and promotes the transfer of electrons between complexes. Cytochrome C, which receives electrons from coenzyme Q10, is a type of heme protein containing heme iron. 5-aminolevulinic acid (5-ALA) is the source of this heme iron. NAD, coenzyme Q10, and cytochrome C (heme iron) contribute to ATP production and are important components that activate mitochondria. The inventors have conducted extensive research into whether mitochondrial activation can also be applied to improving sperm motility, and as a result, Based on the test described below The effectiveness was confirmed.

[0018] As described above, according to this embodiment, a combination drug containing nicotinamide mononucleotide (NMN), coenzyme Q10, and 5-aminolevulinic acid (5-ALA) as essential ingredients is prepared, and It has been confirmed that this compound is more effective at increasing ATP (Adenosine tri-phosphate) production and suppressing ROS (Reactive Oxygen Species) production than when nicotinamide mononucleotide (NMN), coenzyme Q10, and 5-aminolevulinic acid (5-ALA) are used individually. In other words, the action of the three components can increase ATP production and suppress ROS production. [Example]

[0019] Next, according to this embodiment A combination drug that improves ATP production The results of the efficacy confirmation test will be explained. In this example, sperm from asthenozoospermia patients were used with the approval of the Tokushima University Hospital Life Science and Medical Research Ethics Committee. The analysis was performed using the sperm motility analysis system SMAS (Sperm Motility Analysis System), which allows for objective numerical analysis.

[0020] · Combination drug (P3) Preparation of Example 1 A combination drug that improves ATP productionA combination drug (P3) containing three ingredients, nicotinamide mononucleotide (NMN), coenzyme Q10, and 5-aminolevulinic acid (5-ALA), was prepared as a test drug. For efficacy confirmation tests, the concentrations of these three ingredients were adjusted to 0.001%, 0.01%, and 0.1% by mass, respectively. The concentrations were adjusted using m-HTF Medium (Nihon Medical Equipment, product number 9600-002) for sperm.

[0021] Measurement of ATP levels in sperm ATP production was analyzed using the ATP Assay Kit-Luminescence (Dojindo Laboratories, Part Number: A550). 100 μL of the ATP standard solution and each sperm suspension was added to wells of a 96-well white microplate. ATP standard solutions were prepared by serial dilution in Modified HTF Medium to 2.5, 1.25, 0.625, 0.313, 0.156, 0.078, 0.039, and 0 μM. Next, 100 μL of working solution was added to each well. The microplate was covered with aluminum foil, shaken for 2 minutes, and then incubated at room temperature for 10 minutes. Luminescence was measured using a SpectraMAX multimode plate reader. TM Measurement was performed using i3 (Molecular Devices Japan). Cellular ATP concentration was calculated from the calibration curve.

[0022] Measurement of sperm mitochondrial ROS levels MitoSOX TM Mitochondrial Superoxide Indicators for live-cell imaging (M36008, Thermo Fisher Scientific KK) were used to analyze the intracellular production of sperm mitochondrial ROS. Sperm samples were immersed in 500 μL of MitoSOX. TM The cells were incubated with Red reagent working solution (5 μM) at 37°C for 10 minutes in the dark. TMMitochondrial ROS levels were analyzed by flow cytometry using a 486 / 42 nm bandwidth filter on a Becton Dickinson flow cytometer. A total of 10,000 sperm-specific events were analyzed, and the positive rate was calculated.

[0023] Example 1 A combination drug that improves ATP production Similar tests were conducted on nicotinamide mononucleotide (NMN), coenzyme Q10, and 5-aminolevulinic acid (5-ALA) as Comparative Examples 1 to 3. These are referred to as Comparative Example 1: NMN, Comparative Example 2: Q10, and Comparative Example 3: 5-ALA.

[0024] -Effects on sperm motility The results of the motility rate at each concentration (0% by mass (untreated), 0.001% by mass, 0.01% by mass, 0.1% by mass, 0.1% by mass) of Example 1 (P3), Comparative Example 1 (NMN), Comparative Example 2 (Q10), and Comparative Example 3 (5-ALA) are shown in Figure 2. As shown in the results of Figure 2, the motility rate decreased in a time-dependent manner when untreated. In each example, the motility rate was maintained 1 hour and 3 hours after mixing of each agent. Among them, Example 1 (P3) showed an increase in motility rate (particularly notable at 0.01% by mass). This effect of increasing motility is exceptional and not seen in Comparative Examples 1 to 3.

[0025] -Effects on ATP production and ROS production Figure 3 shows the results of measuring ATP production and ROS production at 0.01% by mass, at which the effect on sperm motility was evident, and one hour after mixing with the drug. As can be seen from the results in Figure 3, ATP production was unchanged in the cases of Comparative Examples 1 to 3 when used alone compared to the untreated group. On the other hand, APT production was significantly increased in the combination drug of Example 1 (P3) compared to the cases of Comparative Examples 1 to 3 when used alone. Furthermore, with regard to ROS production, although ROS production was suppressed in Comparative Examples 1 to 3 compared to the untreated group, it was clear that the combination drug of Example 1 (P3) had a higher suppression rate.

Claims

1. A sperm motility enhancer characterized by being a combination drug containing nicotinamide mononucleotide (NMN), coenzyme Q10, and 5-aminolevulinic acid (5-ALA) as essential ingredients.

2. The sperm motility improver according to claim 1, characterized in that the three components, nicotinamide mononucleotide (NMN), coenzyme Q10, and 5-aminolevulinic acid (5-ALA), are contained in a mass ratio of 0.25 to 0.80:0.06 to 0.80:0.005 to 0.80, where the total amount of the three components is 1.

3. The sperm motility enhancer according to claim 1, wherein any one of the nicotinamide mononucleotide (NMN), the coenzyme Q10, and the 5-aminolevulinic acid (5-ALA) may be contained in the form of a derivative or a salt.

4. The sperm motility improver according to any one of claims 1 to 3, characterized in that it is used for infertility treatment in adult men with reduced sperm motility and / or reduced sperm concentration, or for pregnancy efforts in adult men.

5. The sperm motility improver according to any one of claims 1 to 3, characterized in that the sperm motility improver is used for breeding animals.

6. The sperm motility improver according to any one of claims 1 to 3, characterized in that the sperm motility improver is used by adding it to semen.

7. The sperm motility enhancer according to any one of claims 1 to 3, characterized in that the sperm motility enhancer is in the form of a tablet, powder, granule, dry syrup, capsule, liquid, or gel, and is administered orally or parenterally.

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