Composition for delaying senescence and application thereof

By optimizing the component ratio in the anti-aging composition, combining NAD precursors, flavonoids and coenzymes, the side effects of NMN in the use of compounds such as NMN are solved, and a safer and more effective anti-aging effect is achieved.

CN119856778APending Publication Date: 2025-04-22SHANGHAI CELL THERAPY GROUP CO LTD
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Patent Information

Application Number
CN202311326936.9
Authority / Receiving Office
CN · China
Patent Type
Applications(China)
Current Assignee / Owner
Filing Date
2023-10-13
Publication Date
2025-04-22

AI Technical Summary

Technical Problem

Existing NAD+ precursor compounds such as NMN can easily lead to side effects such as ignition and oral ulcer during use, and excessive betaine may cause adverse reactions such as nausea and abdominal pain, affecting the anti-aging effect.

Method used

Using a composition containing NAD or its precursor, flavonoids and coenzymes, the side effects are reduced and anti-aging effects are improved by optimizing the proportion of components such as NMN, quercetin, PQQ and vitamin B complex.

Benefits of technology

Effectively alleviate the irritation reaction caused by NMN, reduce the degree of oral ulcers, reduce the side effects of the overall composition, and improve the anti-aging effect, and enhance the safety and breadth of the composition.

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Abstract

The invention relates to the field of daily chemical health care, in particular to an anti-aging composition which contains NAD (nicotinamide adenine dinucleotide) or a precursor thereof, flavonoid and coenzyme and is small in side effect and good in anti-aging effect.
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Description

Technical Field

[0001] The invention relates to the field of daily chemical health care, and in particular to a composition for delaying aging and application thereof. Background Art

[0002] Human aging is the physiological, metabolic and functional changes that gradually occur in various systems, organs and tissues of the body after they grow, develop and mature. Nicotinamide mononucleotide (NMN) is a synthetic intermediate of nicotinamide adenine dinucleotide (NAD+) and has attracted much attention as a substance that inhibits aging. Experiments have shown that NMN controls the activity of the longevity gene "sirtuin" by converting it to NAD+. When NMN is applied to mice, it shows anti-aging effects.

[0003] NMN is a substance produced naturally in the body, and its production capacity gradually decreases as the human body ages. Therefore, in order to delay aging, it can be achieved by supplementing anti-aging functional foods and medicines containing NMN.

[0004] In the prior art, in order to cooperate with the use of NMN, other ingredients are usually added to form an anti-aging composition together. For example, in the prior art CN113170889A, a compound anti-aging composition is recorded, which includes NMN, PQQ, quercetin and its betaine. Among them, quercetin belongs to flavonoids (Bioflavonoids), which is a class of polyphenolic compounds widely distributed in the plant kingdom (mainly in the leaves, flowers, roots, stems, and fruits of plants). Its structure contains phenolic hydroxyl groups, which can react with free radicals to generate stable semiquinone free radicals, thereby effectively removing free radicals and achieving an antioxidant effect; there are also many protective mechanisms for the cardiovascular system, such as reducing blood lipid content, inhibiting LDL oxidation, inhibiting platelet aggregation, reducing capillary permeability and fragility, etc.; flavonoids such as tea polyphenols and soy isoflavones also have the effect of inhibiting tumors. PQQ belongs to coenzymes, which is a general term for a large class of organic cofactors and is an essential factor for enzyme-catalyzed redox reactions, group transfers, and isomerization reactions. Betaine is widely present in animals and plants, and has anti-tumor, anti-hypertensive, anti-peptic ulcer and gastrointestinal dysfunction effects.

[0005] However, the inventors found in their research that NMN and other NAD+ precursor compounds can cause inflammation in the human body during actual use, and have side effects such as oral ulcers. Especially when the NMN content in the formula is too high, such side effects are particularly obvious. Excessive betaine may also cause side effects such as nausea, abdominal pain, and diarrhea. In severe cases, it can aggravate diseases such as hemochromatosis and Wilson's disease. How to reduce these side effects while maintaining or improving the anti-aging effect is still a technical problem that needs to be solved in this field. Summary of the invention

[0006] The inventors, based on a large number of experiments, provide a composition for delaying aging, which has little side effects and good anti-aging effects.

[0007] The technical solution of the present invention is as follows:

[0008] A composition comprising NAD or its precursor, flavonoids and coenzymes.

[0009] In some embodiments, the NAD precursor is selected from one or more of tryptophan, quinolinic acid, nicotinic acid (NA), nicotinamide (NAM), nicotinamide mononucleotide (NMN), nicotinamide riboside (NR), or alimentarily or pharmaceutically acceptable salts, derivatives or prodrugs thereof; preferably nicotinamide mononucleotide (NMN).

[0010] In some embodiments, the flavonoid is selected from one or more of quercetin, dihydroquercetin, fisetin, catechin, gallin, resveratrol, hesperetin, preferably quercetin and / or dihydroquercetin.

[0011] In some embodiments, the coenzyme is selected from at least one of glutathione or its derivatives, adenosine triphosphate and its derivatives, pyrroloquinoline quinone or its derivatives, adenosine methionine or its derivatives, coenzyme A or its derivatives, and coenzyme Q or its derivatives, preferably pyrroloquinoline quinone and / or coenzyme Q10.

[0012] In some specific embodiments, the weight ratio of NAD or its precursor, flavonoid and coenzyme is (250-350):(10-30):(5-15), preferably 30:2:1.

[0013] In some specific embodiments, the composition further contains complex vitamins, preferably at least two of complex vitamins B, vitamin C, and vitamin E, and preferably contains complex vitamins B, vitamin C, and vitamin E.

[0014] In some specific embodiments, the vitamin B complex contains at least any two of vitamin B1, vitamin B2, vitamin B3, vitamin B5, vitamin B6, vitamin B7, vitamin B9, and vitamin B12; preferably, it is a combination of vitamin B1, vitamin B2, and vitamin B6; further preferably, it is a combination of vitamin B1, vitamin B2, vitamin B6, and vitamin B12.

[0015] In some more specific embodiments, the weight ratio of vitamin B1, vitamin B2 and vitamin B6 is (5-10):(5-15):(5-10), preferably 9:10:8.

[0016] In the above composition, the ratio of NAD or its precursor, flavonoids, coenzymes and complex vitamins is (250-350): (10-30): (5-15): (35-45), preferably 30:2:1:4.

[0017] In a specific embodiment, the compound composition further contains calcium pantothenate.

[0018] The invention also provides an edible composition for delaying aging, which comprises the composition described above.

[0019] In some embodiments, the edible composition further contains a food-acceptable excipient, wherein the excipient has any of the following characteristics:

[0020] 1) containing a flavoring agent, wherein the flavoring agent is selected from one or more of lactose, stevioside, xylitol, honey, syrup, and peppermint oil;

[0021] 2) Containing dosage form excipients, wherein the dosage form excipients are selected from one or more of calcium stearate, magnesium stearate, hydroxypropyl methylcellulose, microcrystalline cellulose, silicon dioxide, and maltodextrin.

[0022] The invention also provides the use of the above-mentioned compound composition in the preparation of the following products:

[0023] (1) Anti-aging products;

[0024] (2) Products that improve sleep

[0025] (3) Products that enhance immunity;

[0026] (4) Antioxidant products.

[0027] In practical applications, the product is one or more of solid beverages, liquid beverages, dairy products, seasoning powders, nutritional products, and oral health care products.

[0028] The beneficial effects of the present invention are:

[0029] 1. By increasing the intake of complex vitamins, especially B complex vitamins, the inflammation reaction caused by NMN can be effectively alleviated, the severity of oral ulcers can be reduced, and the side effects of the entire composition can be reduced.

[0030] 2. The formula does not contain betaine, which avoids possible side effects such as nausea, abdominal pain, diarrhea, etc. It is safer when taken as a health supplement for a long time.

[0031] 3. Calcium pantothenate is added to supplement calcium, increase the effective ingredients of the formula, and cover a wider range of people. DETAILED DESCRIPTION

[0032] The present invention is further described below by way of examples, but the present invention is not limited to the scope of the examples. The experimental methods in the following examples without specifying specific conditions are carried out according to conventional methods and conditions, or selected according to the product specifications.

[0033] Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure belongs.

[0034] Example 1 Composition of the invention

[0035] Formula 1: The ingredients and their weight ratios of the composition are:

[0036] NMN: 30 servings

[0037] Dihydroquercetin: 2 parts

[0038] PQQ: 1 serving

[0039] Multivitamins: 4 servings

[0040] Among them, the multivitamin contains vitamins B1, B2, and B6 in a weight ratio of 9:10:8.

[0041] Formula 2: The ingredients and their weight ratios of the composition are:

[0042] NMN: 30 servings

[0043] Dihydroquercetin: 2 parts

[0044] PQQ: 1 serving

[0045] Multivitamins: 4 servings

[0046] Among them, the multivitamin contains vitamin C, vitamin E, and vitamin B complex in a weight ratio of 30:7.3:2.7. In the vitamin B complex, the weight ratio of vitamin B1, B2, and B6 is 9:10:8.

[0047] Formula 3: The ingredients and their weight ratios of the composition are:

[0048] NMN: 30 servings

[0049] Dihydroquercetin: 2 parts

[0050] PQQ: 1 serving

[0051] Multivitamins: 4 servings

[0052] Calcium pantothenate: 0.2 parts

[0053] Among them, the multivitamin contains vitamin C, vitamin E, and vitamin B complex in a weight ratio of 30:7.3:2.7. In the vitamin B complex, the weight ratio of vitamin B1, B2, and B6 is 9:10:8.

[0054] Example 2 Human body verification of the anti-aging effect of the composition of the invention

[0055] 2.1 Experimental Grouping:

[0056] The proportions of complex vitamins in Formula 2 and Formula 3 were used, and the proportions of other ingredients were shown in Table 2.1. The capsules were filled (capsule shells were purchased from Shanghai Red Star Capsule Co., Ltd.). The amount of microcrystalline cellulose as the filler was determined based on whether the capsules were fully filled. Each capsule contained 500 mg of total ingredients.

[0057] Table 2.1

[0058] Grouping NMN Dihydroquercetin PQQ Multivitamins Calcium Pantothenate Magnesium Stearate Silicon dioxide Blank Group 0 0 0 0 0 10 5 Experimental Group 1 150 10 5 0 0 10 5 Experimental Group 2 250 10 5 0 0 10 5 Experimental Group 3 300 10 5 0 0 10 5 Experimental Group 4 300 20 10 0 0 10 5 Experimental Group 5 350 20 10 0 0 10 5 Experimental Group 6 300 20 10 35 0 10 5 Experimental Group 7 300 20 10 40 0 10 5 Experimental Group 8 300 20 10 45 0 10 5 Experimental Group 9 300 20 10 40 1 10 5 Experimental Group 10 300 20 10 40 2 10 5

[0059] 2.2 Experimental methods:

[0060] Subject grouping: 50 female volunteers were randomly divided into 10 experimental groups, 5 in each group, aged 32-51 years old. They were healthy, had no skin diseases, no history of allergies, and had non-sensitive skin. They could complete the evaluation work as required and truly and objectively reflect their feelings after use.

[0061] Usage: Volunteers in each group took the medicine separately, 2 times a day, 1 capsule each time, for 5 consecutive days, 2 days off, 4 consecutive cycles, a total of 28 days. VISA digital skin analyzer (USA) and MPA580 skin elasticity tester (Germany) were used to test the depth of wrinkles, skin elasticity, and skin fineness around the eyes, lips, and forehead of the volunteers.

[0062] The scoring criteria are: very satisfied (5 points) (the test results improved by more than 20% compared to before the test); satisfied (3-4 points) (the test results improved by 10-20% compared to before the test); average (1-2 points) (the test results improved by 0-10% compared to before the test); and dissatisfied (0 point) (no improvement in the test results compared to before the test).

[0063] 2.3 Experimental results:

[0064] The results showed that among the three test indicators, skin fineness was the most intuitive improvement indicator, which gradually improved with the increase of NMN dosage. On this basis, increasing the dosage of dihydroquercetin and PQQ further improved the anti-aging effect, and there was a certain improvement in wrinkle depth and skin elasticity.

[0065] Table 2.2

[0066]

[0067] Example 3 Verification of the improvement of side effects of the composition of the invention

[0068] 3.1 Experimental Grouping:

[0069] The proportions of complex vitamins in Formula 2 and Formula 3 are used, and the proportions of other ingredients are shown in Table 3.1. The auxiliary materials are 10 mg of magnesium stearate and 5 mg of silicon dioxide. The filling is capsules (capsule shells are purchased from Shanghai Red Star Capsule Co., Ltd.). The amount of filler microcrystalline cellulose is determined based on whether the capsule is full. Each capsule contains 500 mg of total ingredients.

[0070] Table 3.1

[0071]

[0072] 3.2 Experimental methods:

[0073] Subject grouping: 32 male volunteers were randomly divided into 8 experimental groups, 4 in each group, aged 31-45 years old. They were in good health and could complete the evaluation work as required and truly and objectively reflect their feelings after use.

[0074] Usage: Volunteers in each group take the medicine separately, 2 times a day, 1 capsule each time, for 5 consecutive days, and then take a break for 2 days, for two consecutive cycles, a total of 14 days. Fill in the scoring form according to the discomfort symptoms after taking the medicine.

[0075] The scoring criteria are: 5 points (no discomfort symptoms after taking the medicine), 3-4 points (mild dry mouth symptoms, which are relieved after stopping taking the medicine), generally 1-2 points (symptoms such as dry mouth, bitter mouth, and flushing face exist, which will continue for a period of time after stopping taking the medicine), and 0 points (discomfort symptoms such as oral ulcers and bleeding gums occur).

[0076] 3.3 Experimental results:

[0077] The results showed that compared with the blank group, taking NMN would produce symptoms of getting angry, such as dry mouth and ulcers. After adding vitamin B complex (experimental groups 1-3), the discomfort symptoms of the users improved significantly, and in a dose-dependent manner, but after reaching a certain dose, the effect remained at a plateau. On this basis, adding vitamin E and vitamin C (experimental groups 4-6) can further improve the effect. Compared with the control group, the addition of complex vitamins, especially vitamin B complex, can significantly improve the side effects that may be caused by taking NMN.

[0078] Table 3.2

[0079] Grouping Effect evaluation Blank Group 5.00 Control group 3.25 Experimental Group 1 3.75 Experimental Group 2 4.50 Experimental Group 3 4.25 Experimental Group 4 4.50 Experimental Group 5 4.75 Experimental Group 6 4.50

Claims

1. A composition, characterized in that The composition contains NAD or its precursor, flavonoids and coenzymes.

2. The composition according to claim 1, characterized in that The NAD precursor is selected from one or more of tryptophan, quinolinic acid, nicotinic acid (NA), nicotinamide (NAM), nicotinamide mononucleotide (NMN), nicotinamide riboside (NR), or a food or pharmaceutically acceptable salt, derivative or prodrug thereof; preferably nicotinamide mononucleotide (NMN).

3. The composition according to claim 1 or 2, characterized in that The flavonoids are selected from one or more of quercetin, dihydroquercetin, fisetin, catechin, gallin, resveratrol, and hesperetin, preferably quercetin and / or dihydroquercetin.

4. The composition according to any one of claims 1 to 3, characterized in that The coenzyme is selected from at least one of glutathione or its derivatives, adenosine triphosphate and its derivatives, pyrroloquinoline quinone or its derivatives, adenosine methionine or its derivatives, coenzyme A or its derivatives, and coenzyme Q or its derivatives, preferably pyrroloquinoline quinone and / or coenzyme Q10.

5. The composition according to any one of claims 1 to 4, characterized in that The weight ratio of NAD or its precursor, flavonoid and coenzyme is (250-350):(10-30):(5-15), preferably 30:2:

1.

6. The composition according to any one of claims 1 to 5, characterized in that The composition further contains complex vitamins, preferably at least two of complex vitamins B, vitamin C, and vitamin E, and preferably contains complex vitamins B, vitamin C, and vitamin E.

7. The composition according to claim 6, characterized in that The vitamin B complex contains at least any two of vitamin B1, vitamin B2, vitamin B3, vitamin B5, vitamin B6, vitamin B7, vitamin B9, and vitamin B12; preferably, it is a combination of vitamin B1, vitamin B2, and vitamin B6; further preferably, it is a combination of vitamin B1, vitamin B2, vitamin B6, and vitamin B12.

8. The composition according to claim 7, characterized in that The weight ratio of vitamin B1, vitamin B2 and vitamin B6 is (5-10):(5-15):(5-10), preferably 9:10:

8.

9. The composition according to any one of claims 1 to 8, characterized in that The weight ratio of the NAD or its precursor, flavonoids, coenzymes and complex vitamins is (250-350): (10-30): (5-15): (35-45), preferably 30:2:1:

4.

10. The composition according to any one of claims 1 to 9, characterized in that The compound composition further contains calcium pantothenate.

11. An edible composition for delaying aging, characterized in that: The invention comprises the composition described in any one of claims 1 to 10.

12. The edible composition according to claim 11, characterized in that The edible composition further comprises a food-friendly excipient, wherein the excipient has any of the following characteristics: 1) containing a flavoring agent, wherein the flavoring agent is selected from one or more of lactose, stevioside, xylitol, honey, syrup, and peppermint oil; 2) Containing dosage form excipients, wherein the dosage form excipients are selected from one or more of calcium stearate, magnesium stearate, hydroxypropyl methylcellulose, microcrystalline cellulose, silicon dioxide, and maltodextrin.

13. Use of the compound composition according to any one of claims 1 to 10 in the preparation of the following products: (1) Anti-aging products; (2) Products that improve sleep; (3) Products that enhance immunity; (4) Antioxidant products.

14. The use according to claim 13, characterized in that The product is one or more of solid beverages, liquid beverages, dairy products, seasoning powders, nutritional products and oral health care products.

Citation Information

Patent Citations

  • Compound anti-aging composition, compound anti-aging tablet and preparation method and application of compound anti-aging composition and compound anti-aging tablet

    CN113170889A