An oral anti-aging combination based on the triple interaction of NAD⁺–SIRT1–GH

Abstract

An oral anti-aging combination based on the triple interaction of NAD + -SIRT1-GH, characterized in that it comprises the following components: NAD + -Precursor, resveratrol or an esveratrol-containing reagent, astaxanthin, grape seed extract, vitamin C, L-citrulline, L-ornithine, hydrolyzed collagen, hydrolyzed type II collagen, a zinc chelate and sodium hyaluronate.

Description

TECHNICAL AREA

[0001] The present invention falls within the field of nutritional health and anti-aging technology, in particular it relates to an oral anti-aging combination based on the triple interaction of NAD. + -SIRT1-GH. STATE OF THE ART

[0002] With increasing age, endogenous collagen synthesis and growth hormone (GH) secretion decline significantly, leading to thinning of the dermis, loss of elasticity, and increased oxidative stress. Traditional collagen supplements are primarily based on the direct supplementation of collagen, but they cannot adequately address the problems caused by declining growth hormone, metabolic degradation, and reduced cell repair and regeneration capacity.

[0003] Existing anti-aging formulations mostly focus on individual mechanisms of action, such as collagen or antioxidant supplementation, and do not systematically consider metabolic regulation or hormonal balance, which is why a systemic anti-aging effect has not yet been achieved. Currently, no applications are known that target NAD. + -SIRT1 energy repair axis, the GH pulse-induced mechanism and collagen synthesis combine in an integrated anti-aging system. INVENTIONAL ITEM

[0004] To overcome the aforementioned disadvantages and shortcomings of the prior art, the main objective of the present invention is to provide an oral anti-aging combination based on the triple interaction of NAD. + -SIRT1-GH to provide.

[0005] The oral anti-aging combination of the present invention can be activated by activating NAD. +The drug improves skin aging and systemic metabolic health by targeting the SIRT1 deacetylation pathway and endogenous growth hormone (GH) secretion in a triaxial coupling mechanism. This specifically addresses typical age-related phenotypes such as metabolic deterioration, skin aging, mitochondrial dysfunction, and reduced collagen synthesis.

[0006] The objective of the invention is achieved through the following combination: An oral anti-aging combination based on the triple interaction of NAD + -SIRT1-GH, which includes the following components: NAD + -Precursor, resveratrol or an esveratrol-containing reagent, astaxanthin, grape seed extract, vitamin C, L-citrulline, L-ornithine, hydrolyzed collagen, hydrolyzed type II collagen, zinc chelate and sodium hyaluronate.

[0007] The oral anti-aging combination is based on the triple interaction of NAD. +-SIRT1-GH of the present invention exerts its synergistic anti-aging effect via the following three mechanisms: 1.NAD + -Metabolic layer: By increasing NAD + -Levels support cellular repair and promote energy production; 2. SIRT1 activation layer: Activation of SIRT1 enhances the expression of PGC-1α, which improves mitochondrial biogenesis and antioxidant capacity; 3. GH metabolic layer: By inhibiting somatostatin release, a growth hormone (GH) impulse is triggered during the night, which stimulates the synthesis of IGF-1 and thus increases collagen production and skin thickness.

[0008] Furthermore, the aforementioned NAD + -Precursors include nicotinamide riboside (NR), for example in the form of nicotinamide riboside chloride or nicotinamide mononucleotide (NMN).

[0009] Furthermore, the resveratrol or an esveratrol-containing reagent can be selected from substances such as extracts from the root of Polygonum cuspidatum (Japanese knotweed).

[0010] Furthermore, the individual components of the oral anti-aging combination of the present invention exhibit significant biological activity in their interaction. 1. NAD + -Precursor: In the present invention, nicotinamide riboside (NR) can be used as a precursor to nicotinamide adenine dinucleotide (NAD). + It can be used. This is a form of vitamin B3. As part of the combination, NR can effectively increase NAD levels. + -levels and thus support the restoration of mitochondrial cell function. 2. Antioxidants and glycation inhibition: The combined use of resveratrol or resveratrol-containing preparations such as Polygonum cuspidatum root extract, astaxanthin, grape seed extract, and vitamin C forms a synergistic network of fat- and water-soluble antioxidants. This combination not only offers comprehensive antioxidant protection but also preserves NAD+ levels. + Resveratrol influences glycation levels and SIRT1 activity and acts as a barrier against glycation. It possesses diverse pharmacological properties, including antitumor, cardioprotective, antioxidant, antimicrobial, antiviral, hepatoprotective, anti-inflammatory, and immunomodulatory effects. As a component of the combination, resveratrol can promote SIRT1 activation, enhance mitochondrial biogenesis, and increase antioxidant capacity. 3. GH Activation: L-citrulline increases plasma arginine levels and suppresses the release of somatostatin in the hypothalamus, thereby enhancing nocturnal pulsatile GH secretion. Synergistically with L-ornithine, it promotes the urea cycle, reduces ammonia levels, and stimulates proline synthesis as a collagen precursor, thereby reversing the inhibitory effect of ammonia on GH secretion and stimulating IGF-1 synthesis in the liver. This promotes fibroblast gene expression and hyaluronic acid synthase activity. Hydrolyzed collagen and hydrolyzed type II collagen provide specific tripeptide sequences (e.g., Gly-Pro-Hyp) that activate the TGF-β / Smad signaling pathway in fibroblasts and increase the expression of type I and type III collagen, as well as fibronectin.In combination with sodium hyaluronate and zinc chelate, they improve the mechanical tension of the fascial layer, increase skin elasticity and hydration, reduce fine lines and strengthen the skin structure as well as the elastic properties of the skeleton.

[0011] The oral anti-aging combination according to the invention is based on the triple interaction of NAD. + SIRT1-GH may contain the following daily supplemental dosages of the respective components: NAD + -Precursor: 50-300 mg, e.g. 50 mg, 100 mg, 200 mg, 300 mg; Resveratrol or esveratrol-containing reagents (e.g., extract from Polygonum cuspidatum): in an effective dose of 5-50 mg resveratrol, e.g. 5 mg, 20 mg, 30 mg, 50 mg; Astaxanthin: 1-6 mg, e.g. B. 1 mg, 2 mg, 4 mg, 6 mg; Grape seed extract: 20-100 mg, e.g. B. 20 mg, 50 mg, 80 mg, 100 mg; Vitamin C: 20-100 mg, e.g. B. 20 mg, 50 mg, 80 mg, 100 mg; L-citrulline: 5-30 mg, e.g. B. 5 mg, 10 mg, 20 mg, 30 mg; L-Ornithine: 5-20 mg, e.g. B. 5 mg, 10 mg, 15 mg, 20 mg; Hydrolyzed collagen: 50-200 mg, e.g. 50 mg, 100 mg, 150 mg, 200 mg; Hydrolyzed type II collagen: 20-100 mg, e.g. 20 mg, 30 mg, 50 mg, 100 mg; Zinc chelate: in an effective dose of 3-25 mg elemental zinc, e.g. 3 mg, 10 mg, 15 mg, 25 mg; Sodium hyaluronate: 10-100 mg, e.g. B. 10 mg, 30 mg, 50 mg, 100 mg.

[0012] The orally administered anti-aging combination according to the present invention can be prepared in conventional methods into any orally accepted galenical form, including, but not limited to: capsules, tablets, lozenges, granules, instant powders, pills, globules, suspensions, alcoholic tinctures, tinctures, drops and solutions.

[0013] Specifically, the liquid dosage form suitable for oral administration includes - but is not limited to - pharmaceutically acceptable emulsions, microemulsions, solutions, suspensions, syrups and elixirs.

[0014] Specifically, the solid dosage form suitable for oral administration includes - but is not limited to - capsules, tablets, pills, powders and granules.

[0015] Furthermore, the capsule dosage form includes - but is not limited to - conventional capsule types such as hard capsules and soft capsules.

[0016] Furthermore, the tablets may include - but are not limited to - conventional tablet types such as sugar-coated tablets, film-coated tablets and gastro-resistant tablets.

[0017] Furthermore, the aforementioned dosage forms may contain one or more pharmacologically acceptable excipients or carriers. These pharmacologically acceptable excipients or carriers may include inert components that do not unduly inhibit the biological activity of the compounds. The pharmacologically acceptable excipients or carriers should be biocompatible, meaning that when administered to subjects, they should not cause toxicity, inflammation, immunogenicity, or other undesirable reactions or side effects. Standard drug formulation procedures may be used for their manufacture.

[0018] Furthermore, the carriers or excipients may include diluents, binders, surfactants, wetting agents, adsorbents, lubricants, fillers, disintegrants, preservatives, and the like. These substances are used as needed to support formulation stability, improve the bioavailability of the active ingredients, or produce an acceptable taste or odor upon oral administration. The active ingredients used in such pharmaceutical combinations may be in the form of the pure compounds themselves or, alternatively, as pharmacologically acceptable salts. The preparation may be made, at the discretion of the person skilled in the art, using any suitable dosage form known to them.

[0019] Diluents include, but are not limited to, lactose, sodium chloride, glucose, urea, starch and water.

[0020] Binders include, but are not limited to, starch, pregelatinized starch, dextrin, maltodextrin, sucrose, gum arabic, gelatin, methylcellulose, carboxymethylcellulose, ethylcellulose, polyvinyl alcohol, polyethylene glycol, polyvinylpyrrolidone, alginate and alginate salts, xanthan gum, hydroxypropylcellulose and hydroxypropylmethylcellulose.

[0021] Surfactants include, but are not limited to, polyoxyethylene sorbitan fatty acid esters, sodium dodecyl sulfate, monostearin and cetyl alcohol.

[0022] Wetting agents include, but are not limited to, glycerin and starch.

[0023] Adsorption media include, but are not limited to, starch, lactose, bentonite, silica gel, kaolin and soap clay.

[0024] Lubricants include, but are not limited to, zinc stearate, monostearin, polyethylene glycol, talc, calcium and magnesium stearate, polyethylene glycol, boric acid powder, hydrogenated vegetable oils, sodium stearoyl fumarate, polyoxyethylene sorbitan stearate, monolauric sucrose esters, sodium lauryl sulfate, magnesium lauryl sulfate and magnesium dodecyl sulfate.

[0025] Fillers include, but are not limited to, mannitol (granulated or powdered), xylitol, sorbitol, maltose, erythritol, microcrystalline cellulose, polysaccharides, coupling sugars, glucose, lactose, sucrose, dextrin, starch, sodium alginate, algal polysaccharide powder, agar powder, calcium carbonate and sodium bicarbonate.

[0026] Explosives include, but are not limited to, cross-linked polyvinylpyrrolidone, sodium carboxymethyl starch, low-substituted hydroxypropyl methylcellulose, cross-linked sodium carboxymethylcellulose, and soy polysaccharides.

[0027] The invention further comprises a tablet which contains the above-described oral anti-aging combination based on the triple interaction of NAD. + -SIRT1-GH contains.

[0028] The invention further comprises a capsule containing the above-described oral anti-aging combination based on the triple interaction of NAD. + -SIRT1-GH contains.

[0029] The invention further comprises an oral liquid which contains the above-described oral anti-aging combination based on the triple interaction of NAD. + -SIRT1-GH contains.

[0030] Compared to the prior art, the present invention has the following significant advantages: This invention represents, for the first time, an orally administered anti-aging combination based on the triple interaction of NAD. + -SIRT1-GH, which is activated by NAD +The individual components exert a coordinated effect within this triaxial mechanism of action, influencing the metabolic pathway, the SIRT1 deacetylation mechanism, and endogenous growth hormone (GH) secretion. Test data according to the present invention show that the oral anti-aging combination effectively improves skin aging and systemic metabolism, thereby positively influencing typical age-related phenotypes such as metabolic degeneration, skin aging, mitochondrial dysfunction, and reduced collagen synthesis. EXECUTION FORMS

[0031] The invention is explained in more detail below with reference to exemplary embodiments, although the embodiments of the invention are not limited thereto. All substances used in the examples are commercially available unless otherwise stated. Unless otherwise stated, the described processes are carried out according to conventional methods. Example 1

[0032] An oral anti-aging combination based on the triple interaction of NAD + -SIRT1-GH comprises the following ingredients: Sodium hyaluronate 50 mg, hydrolyzed collagen 80 mg, Polygonum cuspidatum extract 50 mg (resveratrol content approx. 25 mg), astaxanthin 3 mg, zinc chelate (amino acid complexed zinc, zinc AA chelate) with 3 mg elemental zinc, grape seed extract 50 mg, vitamin C 50 mg, L-citrulline 15 mg, L-ornithine 10 mg, hydrolyzed type II collagen 50 mg, nicotinamide riboside chloride 75 mg.

[0033] The aforementioned components are mixed evenly and pressed into tablets to obtain an oral anti-aging tablet. Example 2

[0034] An oral anti-aging combination based on NAD +-SIRT1-GH-Triple Axis comprises the following ingredients: Sodium hyaluronate 70 mg, hydrolyzed collagen 100 mg, Polygonum cuspidatum extract 30 mg (resveratrol content approx. 15 mg), astaxanthin 5 mg, zinc chelate (amino acid complexed zinc, zinc AA chelate) with 5 mg elemental zinc, grape seed extract 30 mg, vitamin C 30 mg, L-citrulline 20 mg, L-ornithine 15 mg, hydrolyzed type II collagen 70 mg, nicotinamide riboside chloride 90 mg.

[0035] The aforementioned active ingredient components are mixed and processed into capsules according to the following steps. Example 3

[0036] An oral anti-aging combination based on NAD +-SIRT1-GH triple axis comprises the following components: sodium hyaluronate 90 mg, hydrolyzed collagen 70 mg, Polygonum cuspidatum extract 40 mg (resveratrol content approx. 20 mg), astaxanthin 2 mg, zinc chelate (amino acid complexed zinc, zinc AA chelate) with 6 mg elemental zinc, grape seed extract 60 mg, vitamin C 20 mg, L-citrulline 10 mg, L-ornithine 10 mg, hydrolyzed type II collagen 60 mg, nicotinamide riboside chloride 100 mg.

[0037] The aforementioned components are homogeneously mixed and processed into an oral anti-aging tablet. Example 4: Proof of effectiveness

[0038] Participants were recruited to take the test product. The efficacy of the oral dietary supplement in reducing wrinkles, firming the skin, improving facial contours, and lifting the jawline was evaluated using instrumental measurements and image analysis. Three groups of participants each took the combinations from embodiments 1 to 3, with 30 people per group. The supplement was taken once daily in the evening, one tablet at a time. After 14 days of continuous use, parameters such as skin elasticity, skin firmness, wrinkle area, lateral facial angle, and jawline angle were tested. Table 1 Test parameters Designation name measuring device Measuring range Description of the measurement parameter Anti-wrinkle effect proportion of the fold area Facial Image Recognition System (VISIA-CR) eye area Proportion of wrinkle area: The smaller the value, the fewer and weaker the wrinkles. Folding surface Fast 3D skin imaging system (PRIMOS CR) corner of eye Wrinkle area: The smaller the value, the fewer and weaker the wrinkles. Tightening effect Skin elasticity value R2 Skin elasticity measuring device MPA580 (cutometer probe) cheek The closer the value is to 100%, the better the skin elasticity. Skin firmness value F4 The smaller the value, the tighter the skin is. improvement Angle measurement Facial image capture system cheek The larger the Test parameters Designation name measuring device Measuring range Description of the measurement parameter facial depth stem (VISIA-CR) The higher the value, the more pronounced the facial depth. Chin line elevation angle of the jawline Facial Image Recognition System (VISIA-CR) chin The smaller the value, the greater the elevation of the jawline.

[0039] The test results show that the oral administration of the anti-aging combination of the present invention led to significant improvements in the following parameters in the subjects, resulting in an anti-wrinkle effect, firming, improvement of facial depth, and lifting of the jawline. The specific data of the test group with the combination from embodiment 1 are listed below.

[0040] The following significance symbols apply: "ns" indicates no statistically significant difference, P > 0.05; "*" indicates a significant difference, 0.01 < P ≤ 0.05; "**" indicates a highly significant difference, 0.001 < P ≤ 0.01; "***" indicates a highly significant difference, P ≤ 0.001. "N" indicates the number of participants, N = 30. Table 1 Skin elasticity value R2 (%) group Before taking (D0) After taking (D 14) Test sample 52,16±10,41 59,70±8,32 Table 2 Rate of change of skin elasticity value R2 group After ingestion (D14) Test sample 14,46% Table 3 Test results of the skin elasticity value R2 time Comparison type N Statistical method p-value significance After ingestion (D14) Compared to before taking the medication 30 Wilcoxon signed-rank test for two-pair samples 0,0000 *** Table 4 Data on skin tightness value F4 (mm*s) group Before taking (D0) After taking (D 14) Test sample 4,43±0,82 3,42±0,65 Table 5: Rate of change of skin firmness score F4 group After ingestion (D14) Test sample -22,80% Table 6 Test results of the skin firmness score F4 time Comparison type N Statistical method p-value significance After taking Compared to before the 30 Wilcoxon sign 0,0000 *** (D14) intake Rank test for two-linked samples Table 7 Data on the proportion of the fold area (%) group Before taking (D0) After taking (D 14) Test sample 2,76±1,65 2,06±1,52 Table 8 Rate of change of the proportion of the fold area (%) group After ingestion (D14) Test sample -25,36% Table 9 Test results for the proportion of the wrinkle area (%) time Comparison type N Statistical method p-value significance After ingestion (D14) Compared to before taking the medication 30 Wilcoxon signed-rank test for two paired samples 0,0000 *** Table 10 Fold area data (mm2) group Before taking (D0) After taking (D 14) Test sample 237,54±13,88 197,55±14,01 Table 11 Rate of change of the fold area (%) group After taking (D14) Test sample -16,84% Table 12 Test results of the fold surface time Comparison type N Statistical method p-value significance After ingestion (D14) Compared to before taking the medication 30 Wilcoxon signed-rank test for two paired samples 0,0000 *** Table 13 Results of the lateral angle (°) group Before taking (D0) After taking (D 14) Test sample 150,43±4,56 154,10±4,25 Table 14 Rate of change of the lateral angle group After taking (D14) Test sample 2,44% Table 15 Test results of the lateral angle time Comparison type N Statistical method p-value significance After ingestion (D14) Compared to before taking the medication 30 Paired t-test 0,0000 *** Table 16 Results of the chin line angle (°) group Before taking (D0) After taking (D 14) Test sample 110,73±4,84 107,78±5,25 Table 17 Rate of change of the jawline angle group After taking (D14) Test sample -2,66% Table 18 Test results of the chin line angle time Comparison type N Statistical method p-value significance After ingestion (D14) Compared to before taking the medication 30 Paired t-test 0,0000 ***

[0041] The test results show that after 14 days of continuous intake of the oral anti-aging combination of the present invention, the skin elasticity R2 in the test area of ​​the subjects shows a highly significant difference compared to the baseline value, with a change rate of 14.46%; the skin firmness value F4 also shows a highly significant difference compared to the baseline value, with a change rate of -22.80%; the proportion of wrinkle area shows a highly significant difference compared to the baseline value, with a change rate of -25.36%; the wrinkle area itself shows a highly significant difference compared to the baseline value, with a change rate of -16.84%; the side profile angle shows a highly significant difference compared to the baseline value, with a change rate of 2.44% and an increase of 3.67°;The mandibular contour angle shows a highly significant difference compared to the baseline value, with a change rate of -2.66% and a tightening of 2.96°. Accordingly, the oral anti-aging combination of the invention, which activates NAD; + -metabolic pathway, SIRT1 deacetylation mechanism and endogenous growth hormone (GH) secretion via a triaxial coupling mechanism, producing an effect against wrinkles, for tightening, for improving facial depth and for lifting the jawline.

[0042] The aforementioned embodiments represent preferred embodiments of the present invention; however, the invention is not limited to these embodiments. All changes, modifications, substitutions, combinations, or simplifications that do not depart from the spirit and essence of the invention are considered equivalent replacements and thus fall within the scope of protection of the present invention.

Claims

[1] An oral anti-aging combination based on the triple interaction of NAD + -SIRT1-GH, characterized by that it includes the following components: NAD + -Precursor, resveratrol or an esveratrol-containing reagent, astaxanthin, grape seed extract, vitamin C, L-citrulline, L-ornithine, hydrolyzed collagen, hydrolyzed type II collagen, a zinc chelate and sodium hyaluronate. [2] An oral anti-aging combination based on the triple interaction of NAD + -SIRT1-GH according to claim 1, characterized by that the daily dosages of the individual components are as follows: NAD +-Precursor: 50-300 mg; Resveratrol or an esveratrol-containing reagent, effective dose according to resveratrol: 5-50 mg; Astaxanthin: 1-6 mg; Grape seed extract: 20-100 mg; Vitamin C: 20-100 mg; L-Citrulline: 5-30 mg; L-Ornithine: 5-20 mg; Hydrolyzed collagen: 50-200 mg; Hydrolyzed type II collagen: 20-100 mg; Zinc chelate, effective dose according to zinc: 3-25 mg; Sodium hyaluronate: 10-100 mg. [3] An oral anti-aging combination based on the triple interaction of NAD + -SIRT1-GH according to claim 1, characterized by that the NAD + -Precursor nicotinamide riboside. [4] An oral anti-aging combination based on the triple interaction of NAD + -SIRT1-GH according to claim 3, characterized by that the nicotinamide riboside comprises at least one compound of nicotinamide riboside chloride and nicotinamide mononucleotide. [5] An oral anti-aging combination based on the triple interaction of NAD+ -SIRT1-GH according to claim 1, characterized by that the combination is manufactured by conventional methods into any orally acceptable dosage form, including at least one of the following: capsules, tablets, lozenges, granules, instant powders, pills, coated tablets, suspensions, alcoholic extracts, tinctures, drops or solutions. [6] An oral anti-aging combination based on the triple interaction of NAD + -SIRT1-GH according to claim 5, characterized by that the dosage form additionally contains one or more pharmacologically acceptable carriers or excipients. [7] An oral anti-aging combination based on the triple interaction of NAD + -SIRT1-GH according to claim 6, characterized bythat the carrier or auxiliary substance is selected to be at least one of the following: diluent, binder, surfactant, wetting agent, adsorbent, lubricant, filler, disintegrant or preservative. [8] A tablet form, characterized by that it contains an active ingredient which, according to one of claims 1 to 4, constitutes the oral anti-aging combination based on NAD + SIRT1-GH three-axis interaction is included. [9] A capsule form characterized in that it contains an active ingredient which, according to one of claims 1 to 4, constitutes the oral anti-aging combination based on NAD + SIRT1-GH three-axis interaction is included. [10] An oral solution, characterized by that it contains an active ingredient which, according to one of claims 1 to 4, constitutes the oral anti-aging combination based on NAD + SIRT1-GH three-axis interaction is included.