NMN-containing biological agent capable of prolonging service life and preparation method

Abstract

The invention provides an NMN-containing biological preparation capable of prolonging the service life and further discloses a preparation method of the biological preparation, beta-nicotinamide mononucleotide and ergothioneine are organically combined to form a formula, the beta-nicotinamide mononucleotide and the ergothioneine are synergistically compatible and mutually synergic, and main functions of telomeres can be prolonged by utilizing the beta-nicotinamide mononucleotide; the antioxidant function of ergothioneine is utilized, the synergistic effect on telomerase activity is further enhanced, the effect that one plus one is larger than two is achieved, and the good longevity promoting effect is achieved. The compound can be used in the fields of health foods, functional foods, dietary supplements, beauty products, medicines and the like, and can be prepared into any medicinal preparation in medicine.

Description

Technical Field

[0001] The present invention provides a biological preparation containing NMN that can prolong lifespan, which is composed of β-nicotinamide mononucleotide and ergothioneine. The present invention also discloses a preparation method of the biological preparation, which can prolong human life and belongs to the technical field of biological products. Background Art

[0002] Longevity is a goal that humans have always pursued. In order to prolong life, people have developed many methods and foods, but the effects are not obvious and practical. Therefore, research and development of products that can promote longevity has far-reaching social significance and huge economic value.

[0003] β-Nicotinamide mononucleotide (NMN) has been shown to have anti-aging, Alzheimer's disease prevention, sleep improvement, cardiovascular protection, immunity enhancement, and blood sugar improvement effects when used alone. Ergothioneine (EGT) has also been shown to have antioxidant, anti-inflammatory, nerve and brain protection, athletic performance enhancement, and anti-aging effects. However, when used alone, neither β-NMN nor EGT has ideal health and medical benefits. For example, prolonged use can lead to less pronounced anti-aging effects. Therefore, the present invention aims to combine the two, demonstrating significant synergistic benefits. Summary of the Invention

[0004] This invention discloses a lifespan-extending biological agent containing NMN and its preparation method. The agent is primarily composed of β-nicotinamide mononucleotide (NMN) and ergothioneine (EGT). Their synergistic combination significantly enhances longevity, surpassing the effects of either agent alone. The agent can be used in health foods, functional foods, dietary supplements, beauty products, and pharmaceuticals.

[0005] The biological preparation containing NMN for prolonging life described in the present invention is composed of β-nicotinamide mononucleotide and ergothioneine, which are prepared in the following proportions by weight: β-Nicotinamide mononucleotide: 250~1250; Ergothioneine: 5~50.

[0006] The method for preparing a life-extending preparation containing NMN according to the present invention comprises the following steps: The invention is obtained by uniformly mixing β-nicotinamide mononucleotide (NMN) and ergothioneine (EGT) in proportion, and filling the mixed components into capsules using a capsule filling plate.

[0007] The active substance of the present invention can be made into preparations such as health foods, functional foods, dietary supplements, and beauty products.

[0008] The active substance of the present invention can be prepared into any pharmaceutical preparation.

[0009] [Usage and Dosage]: Take one tablet (300-1300 mg) once in the morning and evening each day.

[0010]

Main effects

[0011] Experiments have shown that the synergistic combination of β-nicotinamide mononucleotide (NMN) and ergothioneine (EGT) has significant synergistic effects in mitochondrial function, oxidative stress defense, DNA repair and genome stability, inflammation regulation, autophagy and cell cleanup, metabolic regulation, and epigenetic modification. 1. Dual enhancement of mitochondrial function NMN increases intracellular NAD+ levels, activates Sirtuins (such as SIRT1 and SIRT3), enhances mitochondrial energy metabolism (ATP production) and mitophagy (clearing damaged mitochondria). EGT, a strong antioxidant, directly clears reactive oxygen species (ROS) produced by mitochondria, protecting the mitochondrial membrane and electron transport chain (ETC) from oxidative damage, thus producing a synergistic effect.

[0012] The synergistic mechanism is that NMN promotes mitochondrial function and EGT reduces mitochondrial oxidative stress, and the two work together to maintain mitochondrial homeostasis. Increased NAD+ levels can enhance EGT's ability to regenerate antioxidant enzymes (such as the reduced thioredoxin system).

[0013] 2. Dual defense against oxidative stress NMN activates the SIRT1 / FOXO pathway, upregulating endogenous antioxidant enzymes such as superoxide dismutase (SOD) and catalase (CAT). EGT has a direct antioxidant effect, acting as a sulfur-containing antioxidant to directly scavenge hydroxyl radicals (·OH) and peroxynitrite (ONOO⁻), while inhibiting lipid peroxidation, thereby producing a synergistic effect.

[0014] The synergistic mechanism is that NMN enhances the cell's own antioxidant system, while EGT directly neutralizes ROS, forming an "endogenous + exogenous" dual antioxidant network. EGT protects NAD+ synthases (such as NAMPT) from oxidative damage, maintaining the effectiveness of NMN.

[0015] 3. Synergy between DNA repair and genome stability NMN is a substrate for PARP (poly ADP ribose polymerase) through NAD+, which is involved in DNA damage repair. SIRT6 (which is NAD+-dependent) regulates chromatin stability and telomere protection. EGT inhibits DNA damage caused by inflammatory factors (such as NF-κB) by reducing DNA oxidative damage (such as the formation of 8-OHdG).

[0016] The synergistic mechanism is that EGT reduces initial DNA damage, and NMN provides the energy and enzyme activity (PARP / SIRT6) required for repair, jointly delaying genomic instability.

[0017] 4. Complementary Inflammation Regulation NMN inhibits the NF-κB pathway by activating SIRT1, reducing the release of pro-inflammatory cytokines (such as IL-6 and TNF-α). EGT reduces the secretion of inflammatory factors such as IL-1β by inhibiting the activation of NLRP3 inflammasome.

[0018] The synergistic mechanism is that NMN and EGT act on different nodes of the inflammatory pathway (upstream NF-κB and downstream NLRP3), respectively, and the combined effect inhibits chronic low-grade inflammation ("inflammatory aging").

[0019] 5. Synergy between Autophagy and Cell Cleanup NMN activates autophagy-related genes (such as LC3 and ATG5) through the NAD+ / SIRT1 pathway, promoting the clearance of damaged proteins and organelles. EGT reduces oxidative damage, reduces the burden on the autophagy system, and inhibits excessive activation of mTOR (an autophagy inhibitor).

[0020] The synergistic mechanism is that EGT optimizes autophagy efficiency, and NMN directly enhances autophagy activity, jointly delaying cell aging.

[0021] 6. Combined effects of metabolic regulation NMN can improve glucose and lipid metabolism (via AMPK / SIRT1) and enhance insulin sensitivity. EGT can regulate lipid metabolism (inhibit lipid peroxidation) and mitochondrial fatty acid oxidation.

[0022] The synergistic mechanism is that both improve metabolic flexibility and reduce metabolic syndrome-related damage (such as glucotoxicity and lipotoxicity).

[0023] 7. Potential synergistic effects of epigenetic modifications NMN regulates histone acetylation through NAD+-dependent deacetylases (Sirtuins), affecting the expression of aging-related genes. EGT protects the activity of epigenetic modification enzymes (such as DNA methyltransferases and histone modification enzymes) through antioxidant protection.

[0024] The synergistic mechanism is that EGT maintains the stability of epigenetic enzymes, and NMN provides auxiliary factors for epigenetic regulation, which together delay epigenetic lesions.

[0025] The positive effects of the present invention are: β-nicotinamide mononucleotide and ergothioneine are organically combined into a formula, and the two synergistically complement each other to enhance each other's synergy. β-nicotinamide mononucleotide can extend the main function of telomeres; and ergothioneine's antioxidant function is utilized to further enhance the synergistic effect on telomerase activity, achieving a one-plus-one greater-than-two effect, and achieving a good longevity and life-prolonging effect. The present invention can be used in the fields of health foods, functional foods, dietary supplements, beauty products, and pharmaceuticals, and can be made into any medical pharmaceutical preparation. DETAILED DESCRIPTION

[0026] The present invention is further described by way of examples below, which do not limit the present invention in any way. Without departing from the technical solution of the present invention, any modification or alteration of the present invention that can be easily implemented by a person skilled in the art will fall within the scope of the claims of the present invention. Example 1

[0027] Take NMN: 1250 mg, EGT: 5 mg, mix them evenly according to the proportion, and use a capsule filling plate to fill the mixed ingredients into capsules. Example 2

[0028] Take 600 mg of NMN and 25 mg of EGT, mix them evenly according to the proportion, and use a capsule filling plate to fill the mixed ingredients into capsules. Example 3

[0029] Take NMN: 250 mg, EGT: 50 mg, mix them evenly according to the proportion, and use a capsule filling plate to fill the mixed ingredients into capsules.

[0030] The medical effect of prolonging life of the present invention is further demonstrated by the following experiments:

[0031] 1 Main instruments and materials 1.1 Main instruments, apparatus and materials for capsule preparation Instruments and apparatus: balance, capsule filling plate, etc.; Materials: NMN (β-nicotinamide mononucleotide), EGT (ergothioneine), empty capsules, self-sealing plastic bags, etc. 1.2 Main instruments and materials for physiological age determination 1.2.1 Main instruments: Fully automatic nucleic acid extraction instrument: QIAcube Real-time fluorescence quantitative PCR (qPCR) instrument: QuantStudio 5 Ultra-micro-volume spectrophotometer: NanoDrop Fully automatic leukocyte separator: FEGTenius Kabi 1.2.2 Main reagents: Telomere qPCR Detection Kit: Contains telomere primers, single copy gene primers, and SYBR Green Master Mix. Telomere primer pairs: Tel-F: 5′-CGGTTTGTTTGGGTTTGGGTTTGGGTTTGGGTTTGGGTT-3′; Tel-R: 5′-GGCTTGCCTTACCCTTACCCTTACCCTTACCCTTACCCT-3′; Single copy gene primers: 36B4-F: 5′-CAGCAAGTGGGAAGGTGTAATCC-3′; 36B4-R: 5′-CCCATTCTATCATCAACGGGTACAA-3′; Calibrator: standard DNA with known telomere length (HEK293 cell line: T / S=1.0); 2 Methods 2.1 Formulas and Examples Containing NMN 2.1.1 The ingredients and dosage ranges of formulas containing NMN are as follows: NMN 250-1250 mg / day; EGT 5-50 mg / day; 2.1.2 Example Example 1: NMN 1250 mg / day; EGT 5 mg / day; Example 2: NMN 600 mg / day; EGT 25 mg / day; Example 3: NMN 250 mg / day; EGT 50 mg / day; 2.1.3 Capsule preparation Experimental group: Compound capsule group. Use a balance to accurately weigh NMN and EGT according to the ratio of the two ingredients in the example formula. Place them into a self-sealing plastic bag, seal it, and repeatedly invert the self-sealing plastic bag for 10 minutes to mix. Use a capsule filling plate to fill the mixed ingredients into capsules, with an average of 2 capsules per day. Control group 1: NMN capsule group. Use a scale to accurately weigh the NMN in the formula corresponding to the experimental group example. Use a capsule filling plate to fill the NMN into capsules, with an average of 2 capsules per day. Control group 2: EGT capsule group: Use a balance to accurately weigh the EGT in the formula corresponding to the experimental group example, and use a capsule filling plate to fill the EGT into capsules, with an average of 2 capsules per day.

[0032] 2.2 Determination of human physiological age 2.2.1 Experimental groups and testing timing Each example is divided into the following 3 groups: Experimental group: 30 volunteers aged 40-49 years old, regardless of gender. They took one compound capsule each morning and evening for 180 days. Measurements were taken before and after the first 180 days of use. Control group 1: 30 volunteers aged 40-49 years, regardless of gender; took one NMN capsule each morning and evening for 180 days; measurements were taken before and after the first 180 days of treatment; Control group 2: 30 volunteers aged 40-49, regardless of gender, took one EGT capsule each morning and evening for 180 days. Measurements were taken before and after the first 180 days of treatment.

[0033] 2.2.2 Determination method 2.2.2.1 Sample collection and processing The subject should fast for at least 8 hours, and 2 mL of peripheral blood (anticoagulated with EDTA) should be collected. White blood cells should be separated using an automated leukocyte separator. If testing cannot be performed immediately, the blood can be stored at 4°C for ≤24 hours, or at -80°C for long-term storage. Genomic DNA from peripheral blood leukocytes was extracted using a fully automatic nucleic acid extractor, and the extracted DNA samples were measured using an ultra-micro spectrophotometer. The purity was required to be between A260 / A280 of 1.8-2.0 and the concentration ≥20 ng / μL.

[0034] 2.2.2.2 qPCR detection Reaction system: SYBR Green Master Mix 10 μL / well; Primers (10 μM) 0.8 μL each / well; DNA template 10 ng / well; Amplification procedure: Table 1

[0035] Single-copy gene amplification was used as an internal reference. The test product and standard were measured separately, and the ratio between the two (T / S ratio) was calculated.

[0036] 2.2.2.3 Calculation of physiological age and physiological age difference: Based on the measured T / S ratio, calculate physiological age according to the following formula: Physiological age (years) = 44.21 + (−15.28 × ln(T / S ratio)) Calculate the difference in physiological age before and after taking the drug according to the following formula:

[0037] Physiological age difference before and after taking (years) = Physiological age before taking (years) - Physiological age after taking (years) If the result is positive, it indicates that the physiological age has decreased (i.e., life expectancy has been extended); if the result is negative, it indicates that the physiological age has increased (i.e., life expectancy has been shortened); if the result is zero, it indicates that the physiological age has not changed before and after taking the medicine (i.e., it has no effect on life expectancy).

[0038] 3 Results 3.1 Experimental results of Example 1 3.1.1 Experimental results of the experimental group of Example 1 are shown in Table 2: Table 2.

[0039] 3.1.2 Experimental results of the control group of Example 1 are shown in Table 3: Table 3.

[0040] 3.1.3 Experimental results of control group 2 of Example 1 are shown in Table 4: Table 4.

[0041] 3.2 Experimental results of Example 2 3.2.1 Experimental results of the experimental group of Example 2 are shown in Table 5: Table 5.

[0042] 3.2.1 Experimental results of control group 1 of Example 2 are shown in Table 6: Table 6.

[0043] 3.2.1 Experimental results of control group 2 of Example 2 are shown in Table 7: Table 7.

[0044] 3.3 Experimental results of Example 3 3.3.1 Experimental results of the experimental group of Example 3 are shown in Table 8: Table 8.

[0045] 3.3.2 Experimental results of control group 1 of Example 3 are shown in Table 9: Table 9.

[0046] 3.3.3 Experimental results of control group 2 of Example 3 are shown in 10: Table 10.

[0047] 4 Results Analysis and Conclusion 4.1 Example 1 Results Analysis and Conclusion First, the average values ​​of the physiological age differences before and after administration in the three groups of experimental results in Example 1 are calculated, as shown in Table 11 below: Table 11.

[0048] In the experimental group (compound capsule group) of Example 1, the average difference in physiological age before and after administration was 12.1 years, indicating an average reduction in physiological age of 12.1 years. This indicates that the present invention's formula significantly reduces physiological age and thus significantly prolongs lifespan.

[0049] The sum of the average physiological age differences for control group 1 (NMN capsule group) and control group 2 (EGT capsule group) (4.6 + 2.4 = 7.0) yielded a value of 7.0 years. Statistically, the average physiological age difference for the compound capsule group, 12.1 years, was significantly different from 7.0 years. This suggests that the present invention's effect on reducing physiological age (i.e., extending lifespan) is significantly greater than the combined effect of the NMN and EGT capsule groups.

[0050] 4.2 Example 2 Results Analysis and Conclusion First, the average values ​​of the physiological age differences before and after administration in the three groups of experimental results in Example 2 are calculated, as shown in Table 12 below:

[0051] Table 12.

[0052] In the experimental group (compound capsule group) of Example 2, the average difference in physiological age before and after administration was 12.9 years, indicating an average reduction in physiological age of 12.9 years. This indicates that the present invention's formula significantly reduces physiological age and thus significantly prolongs lifespan.

[0053] The sum of the average physiological age differences for control group 1 (NMN capsule group) and control group 2 (EGT capsule group) (5.4 + 1.5 = 6.9) yielded a value of 6.9 years. Statistically, the average physiological age difference for the compound capsule group, 12.9 years, was significantly different from 6.9 years. This suggests that the present invention's effect on reducing physiological age (i.e., extending lifespan) is significantly greater than the combined effect of the NMN and EGT capsule groups.

[0054] 4.3 Example 3 Results Analysis and Conclusion First, the average values ​​of the physiological age differences before and after administration in the three groups of experimental results in Example 3 are calculated, as shown in Table 13 below:

[0055] Table 13.

[0056] In the experimental group (compound capsule group) of Example 3, the average difference in physiological age before and after administration was 10.2 years, indicating an average reduction in physiological age of 10.2 years. This indicates that the present invention's formula significantly reduces physiological age and thus significantly prolongs lifespan.

[0057] The sum of the average physiological age differences for control group 1 (NMN capsule group) and control group 2 (EGT capsule group) (2.3 + 2.0 = 4.3) yields a value of 4.3 years. Statistically, the average physiological age difference for the compound capsule group, 10.2 years, is significantly different from the 4.3 years. This suggests that the present invention's effect on reducing physiological age (i.e., extending lifespan) is significantly greater than the combined effect of the NMN and EGT capsule groups.

[0058] 4.4 Synergistic Effects of the Formula From the above analysis and conclusions, it can be seen that the effects of the compound capsule groups of the three examples in reducing physiological age (extending life span) are significantly greater than the sum of the effects of the NMN capsule group and the EGT capsule group in reducing physiological age (extending life span), indicating that the ingredients of the present invention have a significant synergistic enhancement effect.

[0059] The synergistic mechanism of the ingredients of the present invention mainly includes the following aspects:

[0060] The above test results show that the formula of the present invention has a significant coordinated enhancement effect, and its main mechanism is to achieve the coordinated enhancement effect through dual enhancement of mitochondrial function, dual defense against oxidative stress, synergy of DNA repair and genome stability, complementarity of inflammation regulation, synergy of autophagy and cell clearance, combined effect of metabolic regulation and potential synergy of epigenetic modification.

Claims

1. A biological preparation containing NMN that can prolong life, characterized in that It is mainly made of β-nicotinamide mononucleotide (NMN) and ergothioneine (EGT) in the following weight ratios: β-Nicotinamide mononucleotide (NMN): 250~1250; Ergothioneine (EGT): 5~50.

2. The method for preparing a biological agent containing NMN that can prolong lifespan as claimed in claim 1, comprising the following steps: Mix β-nicotinamide mononucleotide (NMN) and ergothioneine (EGT) evenly according to a certain proportion, and use a capsule filling plate to fill the mixed components into capsules to obtain the product.

3. Biological preparations such as health foods, functional foods, dietary supplements, and beauty products containing the active substance according to claim 1.

4. Any biological preparation containing the active substance according to claim 1.

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