Anti-aging composition

Abstract

The invention relates to an anti-aging composition, and belongs to the field of medicines and health-care product preparations. The composition is a microcapsule assembled by a water-soluble wall material, a first core material, a fat-soluble wall material and a second core material which are sequentially coated from outside to inside, and the first core material comprises beta-nicotinamide mononucleotide (NMN), nicotinamide ribose (NR), ergothioneine and trimethylglycine (TMG); the second core material comprises resveratrol, curcumin, pyrroloquinoline quinone (PQQ) and spermidine, and is dissolved in medium chain triglyceride (MCT oil) containing an antioxidant tocopherol. According to the dosage form, physical isolation and differentiated release of water-soluble and fat-soluble components are realized, and the problems of incompatibility among the components, poor stability, low bioavailability and the like are solved. Through the multi-target synergistic effect, the composition can effectively improve the NAD + level and enhance the mitochondrial function so as to improve the skin state and delay senescence.

Description

Technical Field

[0001] This invention belongs to the field of pharmaceutical and health product formulations, specifically relating to an anti-aging composition with synergistic effects. In particular, this invention relates to an anti-aging composition using a specific dosage form, its preparation method, and its application in delaying aging and improving related functions. Background Technology

[0002] Modern biological research indicates that the aging process is closely related to multiple molecular mechanisms, among which mitochondrial dysfunction and cellular energy metabolism disorders are considered one of the core driving factors. As the cell's "energy factory," reduced mitochondrial activity leads to decreased ATP production, which in turn causes a decline in cell repair capacity and increased oxidative stress levels, ultimately manifesting as aging phenotypes such as loose skin, memory loss, and weakened motor skills. Meanwhile, NAD... + Nicotinamide adenine dinucleotide (NAD), a key coenzyme involved in mitochondrial energy metabolism, shows a significant decreasing trend in its levels with age, while NAD... + Insufficient levels can further exacerbate mitochondrial dysfunction, creating a vicious cycle in the aging process. Most anti-aging products on the market today rely on single active ingredients, such as simply supplementing with NMN or resveratrol, which fails to achieve the synergistic effect of multi-target intervention in the aging mechanism. More importantly, existing products suffer from significant deficiencies in dosage form design: on the one hand, water-soluble active ingredients like NMN and NR are easily degraded by light and oxygen, resulting in poor product stability and low utilization of active ingredients; on the other hand, while fat-soluble ingredients like resveratrol and curcumin have clear antioxidant and Sirtuins protein family activation effects, their high fat solubility and poor water solubility lead to low bioavailability and insufficient intestinal absorption after oral administration, preventing them from fully exerting their physiological activity. Furthermore, some products blindly increase the content of single ingredients in pursuit of efficacy, which not only increases the risk of gastrointestinal irritation but may also disrupt metabolic balance in the body, potentially causing safety hazards. Summary of the Invention

[0003] The purpose of this invention is to provide an anti-aging composition with multi-target synergistic effects, which systematically enhances mitochondrial function through the synergistic combination of specific active ingredients.

[0004] The objective of this invention can be achieved through the following technical solutions: In a first aspect, the present invention provides an anti-aging composition, wherein the particle morphology of the composition is a microcapsule assembled from a water-soluble wall material, a first core material, a fat-soluble wall material, and a second core material, which are sequentially coated from the outside to the inside, wherein: The raw materials of the first core material include β-nicotinamide mononucleotide (NMN), nicotinamide ribose (NR), ergothioneine and trimethylglycine (TMG), and the first core material is formed from a dispersion of its raw materials; The raw materials for the second core material include liposomed resveratrol, liposomed curcumin, pyrroloquinoline quinone and spermidine, and the second core material is formed by an oily dispersion of its raw materials dissolved in MCT oil.

[0005] The double-layer wall structure physically isolates the water-soluble first core material from the fat-soluble second core material, preventing interference or degradation between the water-soluble and fat-soluble components. This effectively solves problems such as physical incompatibility, easy moisture absorption, inter-component interaction, and chemical instability that exist when the two are simply mixed.

[0006] Preferably, based on a single capsule, the raw materials of the first core material include: NMN 250-500 mg, NR 100-300 mg, ergothioneine 5-10 mg, and TMG 5-20 mg.

[0007] Preferably, the raw materials of the first core material, per single capsule, include: 300 mg NMN, 100 mg NR, 8 mg ergothioneine, and 10 mg TMG.

[0008] Preferably, the raw materials of the second core material, calculated per single capsule, include: 20-30 mg of resveratrol, 40-60 mg of curcumin, 10-20 mg of PQQ, and 0.5-2 mg of spermidine.

[0009] Preferably, the raw materials of the second core material, calculated per single capsule, include: 25 mg of resveratrol, 50 mg of curcumin, 15 mg of PQQ, and 1 mg of spermidine.

[0010] Therefore, TMG is used to convert NMN / NR to NAD. + Provides methyl groups; enhances NAD. + The level enhanced the activation efficacy of resveratrol on Sirtuins; PQQ and spermidine synergistically promoted mitophagy; MCT oil promoted the absorption of fat-soluble components.

[0011] The capsule rapidly disintegrates in the stomach, releasing NMN, NR, and NAD+ in the blood. + Levels begin to rise rapidly, immediately activating the Sirtuins pathway and cellular energy metabolism. At this point, the contents may have just entered the duodenum and have not yet completely dissolved.

[0012] Once the water-soluble components are functioning, the contents dissolve in the intestines, while the fat-soluble components, emulsified by bile, are absorbed along with MCT oil and enter the systemic circulation via the lymphatic system. This process is slow and sustained, providing long-lasting anti-inflammatory, antioxidant, and mitochondrial support.

[0013] This combination of fast and slow release patterns effectively prevents all components from reaching their peak levels simultaneously, thus avoiding wasting some of the drug's efficacy, prolonging the duration of drug action, and achieving continuous protection. It also avoids stomach discomfort caused by the accumulation of high concentrations of fat-soluble components in the stomach.

[0014] Preferably, the raw material for the second core material further includes tocopherol at a weight of 0.05%-0.2% of the MCT oil.

[0015] Preferably, the water-soluble wall material is hydroxypropyl methylcellulose (HPMC); the fat-soluble wall material is gelatin.

[0016] Secondly, the present invention provides a method for preparing an anti-aging composition, comprising the following steps: (1) The second core material raw material and tocopherol are dissolved in MCT oil to form an oil phase, which is then encapsulated and shaped using a fat-soluble wall material to obtain the contents; (2) The capsule shell is made using a water-soluble wall material; (3) Place the pre-made contents into the lower half of the capsule, and then fill the surrounding cavity with the uniformly mixed first core material under the protection of inert gas. (4) Fit the capsule cap and lock it to complete the final sealing of the capsule.

[0017] Inert gas is introduced during capsule filling to effectively prevent the degradation of easily oxidized active ingredients such as ergothioneine during production and storage, ensuring the product's core efficacy. A specific amount of tocopherol (0.05%-0.2%) is added to the oil phase of the contents as an antioxidant, specifically addressing the oxidative rancidity issues of fat-soluble components and the MCT oil phase during the process, further guaranteeing the product's stability and safety.

[0018] The beneficial effects of this invention are: The hierarchical structure of "water-soluble wall material - first core material - lipid-soluble wall material - second core material" constructed in this invention is a precise "compartmentalization and controlled release" system design based on the physicochemical properties of the components and the metabolic needs in vivo. This design fundamentally solves the technical obstacles that a single wall material system cannot overcome: First, by constructing independent microenvironments of hydrophilic (HPMC) and hydrophobic (gelatin) components respectively, the problem of mutual damage and decreased stability caused by the coexistence of water and oil components is completely eliminated; Second, by utilizing the different solubility characteristics of the two wall materials in the gastrointestinal tract, the rapid release of water-soluble components and the delayed release of lipid-soluble components are precisely achieved, forming a synergistic rhythm of "rapid start-up" and "continuous maintenance"; Finally, this structure conforms to the human body's absorption physiology, guiding water-soluble components to be absorbed via the portal vein, while lipid-soluble components are absorbed via the lymphatic system under the transport of MCT oil to avoid the first-pass effect of the liver, thereby systematically maximizing the bioavailability and overall efficacy of each active component.

[0019] Specifically, the water-soluble components in the capsules are rapidly released and absorbed in the upper digestive tract, quickly increasing NAD5 levels in the body. + At the level of absorption, it activates core anti-aging pathways; while the fat-soluble components in the contents are slowly released in the middle digestive tract and efficiently absorbed through the lymphatic system with the help of MCT oil, bypassing the first-pass effect of the liver, thus providing sustained and more bioavailable mitochondrial functional support and autophagy induction. This triple synergy in absorption time, spatial pathway, and physiological function ensures that each active component can exert its effects efficiently and orderly in the body. Detailed Implementation

[0020] To further illustrate the technical means and effects of the present invention in achieving its intended purpose, the following detailed description of the specific implementation methods, structures, features, and effects of the present invention, in conjunction with embodiments, is provided below.

[0021] Currently, the industry requires ideal anti-aging products to meet three core requirements simultaneously: first, to achieve synergistic compatibility between water-soluble and fat-soluble active ingredients, thereby regulating aging-related mechanisms through multiple pathways; second, to adopt special dosage form designs to protect the stability of easily degradable ingredients and extend the product's shelf life; and third, to improve the bioavailability of fat-soluble ingredients, ensuring that active ingredients can effectively reach their target sites.

[0022] Through systematic research and verification, the inventors discovered that water-soluble wall materials can protect water-soluble components from the influence of the external environment, while fat-soluble wall materials can provide a suitable dissolution environment for fat-soluble components. By utilizing the different properties, functions, and absorption differences of different active ingredients, they can be distributed to their specific locations, thereby achieving differentiated release of active ingredients in the body and further optimizing absorption and bioavailability.

[0023] The inventors have innovatively combined a double-layer wall material with a specific combination of active ingredients, achieving breakthroughs in resolving physicochemical incompatibilities, optimizing bioavailability, protecting the stability of core active ingredients, and realizing multi-pathway synergistic anti-aging. This completes the invention.

[0024] Example 1 An anti-aging composition comprising: Prescription (per 1000 tablets): The raw materials of the first core material: NMN 300 g, NR 100 g, ergothioneine (microencapsulated powder) 8 g, TMG 10 g.

[0025] The raw materials for the second core material are: 25 g of resveratrol (liposomes), 50 g of curcumin (liposomes), 15 g of PQQ, 1 g of spermidine, 200 g of MCT oil, and 0.2 g of tocopherol.

[0026] Preparation process: Preparation of contents: Resveratrol, curcumin, PQQ, and spermidine were added sequentially to MCT oil and stirred in a 50°C water bath until completely dissolved. Then, tocopherol was added and stirred until homogeneous to form the oil phase. Gelatin was used as the fat-soluble wall material, and the oil phase was pressed into oval-shaped contents with each pellet containing ~291 mg of contents using a pellet press.

[0027] Preparation of capsule shells: Hydroxypropyl methylcellulose (HPMC) is used as a water-soluble wall material to prepare the capsule body and capsule cap.

[0028] Nesting and filling: Using a dedicated nesting capsule assembly device, the contents obtained in step (1) are precisely placed into the lower half of the capsule prepared in step (2). Subsequently, under the protective environment of continuous high-purity nitrogen (99.99%), the uniformly mixed first core material is filled into the surrounding cavity.

[0029] Sealing and sealing: Fit the capsule cap onto the capsule and lock it in place to complete the final sealing of the capsule.

[0030] Example 2 An anti-aging composition comprising: Prescription (per 1000 tablets): The raw materials of the first core material: NMN 250 g, NR 150 g, ergothioneine (microencapsulated powder) 10 g, TMG 5 g.

[0031] The raw materials for the second core material are: 30 g of resveratrol (liposomes), 40 g of curcumin (liposomes), 20 g of PQQ, 0.5 g of spermidine, 220 g of MCT oil, and 0.11 g of tocopherol.

[0032] The preparation process is the same as in Example 1.

[0033] Example 3 An anti-aging composition comprising: Prescription (per 1000 tablets): The raw materials of the first core material: NMN 500 g, NR 100 g, ergothioneine (microencapsulated powder) 5 g, TMG 20 g.

[0034] The raw materials for the second core material are: 20 g of resveratrol (liposomes), 60 g of curcumin (liposomes), 10 g of PQQ, 2 g of spermidine, 180 g of MCT oil, and 0.36 g of tocopherol.

[0035] The preparation process is the same as in Example 1.

[0036] Example 4 Human clinical trials validate anti-aging effects: A randomized, double-blind, placebo-controlled trial design was adopted. Participants: Fifty healthy adults aged 45-60 years were recruited, with an equal number of men and women. They were randomly assigned to two groups.

[0037] Intervention group (n=25): Daily oral administration of the anti-aging capsules of the present invention prepared in Example 1.

[0038] Control group (n=25): Daily oral administration of placebo capsules with identical appearance (containing microcrystalline cellulose and maltodextrin).

[0039] The trial period is 3 months. The following tests will be conducted at the start (month 0) and end (month 3): Primary endpoint (core mechanism indicator): NAD + Level detection: Peripheral blood was collected from the subjects, peripheral blood mononuclear cells (PBMCs) were isolated, and intracellular NAD was quantitatively detected using an ELISA kit. + concentration.

[0040] Secondary endpoints (apparent improvement and safety indicators): Skin health assessment: The stratum corneum moisture content and skin elasticity of the inner forearm skin were quantitatively measured using a skin tester.

[0041] Aging-related serum biomarkers: The level of GDF-15 in serum was detected by ELISA (GDF-15 is an emerging biomarker closely related to aging and mitochondrial dysfunction).

[0042] Safety assessment: Blood routine, liver function (ALT / AST), and kidney function (Cr / BUN) indicators were measured.

[0043] Experimental results: The results after 3 months of intervention are shown in the table below: Clinical trials have confirmed that after continuous use of the anti-aging composition of this invention for 3 months: It can significantly increase intracellular NAD+ in human cells. + The level directly verifies the effectiveness of its core biological mechanism in the human body.

[0044] It can significantly improve age-related phenotypic indicators, such as skin hydration and elasticity.

[0045] It can significantly reduce the level of the systemic aging biomarker GDF-15, demonstrating its anti-aging effect at the molecular level.

[0046] It demonstrated good safety and tolerability throughout the trial.

[0047] Comparative Example 1 HPMC capsules containing only 500g of NMN were prepared using the same process as the capsule preparation in Example 1, except that no other active ingredients were added.

[0048] Comparative Example 2 All active ingredients (NMN, NR, ergothioneine, TMG, resveratrol, curcumin, PQQ, spermidine) from the capsules in Example 1 were directly mixed and filled into HPMC capsules. No fat-soluble wall materials, MCT oil, or tocopherol were used.

[0049] Comparative Example 3 The prescription is exactly the same as in Example 1.

[0050] In the preparation process, nitrogen gas is not used for protection during the mixing of the capsule layers; the process is completed in air. The remaining steps are the same as in Example 1.

[0051] Comparative Example 4 The prescription is exactly the same as in Example 1, but without the addition of tocopherol.

[0052] The preparation process is the same as in Example 1.

[0053] Comparative Example 5 The prescription is exactly the same as in Example 1.

[0054] The manufacturing process was changed to: simply mixing the first core material and the second core material (pre-prepared), then encapsulating and shaping them with gelatin. This resulted in a single fat-soluble capsule containing all water-soluble and fat-soluble components.

[0055] Comparative Example 6 The prescription is similar to that of Example 1, but TMG is not added to the capsule layer.

[0056] The preparation process is the same as in Example 1.

[0057] Comparative Example 7 The prescription is similar to that of Example 1, but spermidine is not added to the contents.

[0058] The preparation process is the same as in Example 1.

[0059] Test case 1. Accelerated stability test: Conducted in accordance with ICH Q1A(R2) guidelines.

[0060] Conditions: 40℃±2℃ / 75% RH±5% RH, for 3 months.

[0061] Detection indicators: The retention rates of NMN and ergothioneine were determined by HPLC.

[0062] 2. In vitro anti-aging efficacy test: Human fibroblasts (HFF-1) were used in the in vitro cell experiment. An aging model was established by induction with D-galactose. A model group (which did not receive any treatment) was set up, and its data were used as a baseline.

[0063] Cellular senescence: The percentage of β-galactosidase (SA-β-gal) positive cells was determined using the method described in Dimri et al. (1995) and detected with a β-galactosidase staining kit (Beyotime, #C0602).

[0064] Mitochondrial function: Intracellular ATP content was determined using an ATP assay kit (Beyotime, #S0026) via chemiluminescence immunoassay.

[0065] NAD + Levels: NAD in cell lysates was detected by ELISA. + Concentration, NAD + Horizontal use of NAD + / NADH assay kit (Beyotime, #S0175) was used for determination.

[0066] 3. Animal lifespan test: 18-month-old naturally aged C57BL / 6J mice.

[0067] Protocol: Mice were administered the drug continuously for 6 months. Survival curves were recorded, and the mean remaining lifespan extension rate was calculated. Mice were housed in an SPF-grade environment under standard conditions, and their natural survival time was recorded. Data are expressed as Kaplan-Meier survival curves, and differences between groups were analyzed using the Log-rank test. Mice lifespan extension rate (%) = (Mean remaining lifespan of the drug-treated group - Mean remaining lifespan of the control group) / Mean remaining lifespan of the control group × 100%. Test results: *The positive rate of SA-β-gal in the model group was 41.5% *ATP levels and cellular NAD + All levels are relative percentages compared to the D-galactose-induced aging model group (set as 100%). Examples 1-3 also showed excellent and stable effects on the key indicator of ATP level (135%, 130%, 128%), significantly better than all comparative examples, providing the most direct experimental evidence for improving mitochondrial function and supporting cellular energy metabolism.

[0068] ATP and NAD levels in Comparative Study 6 (without TMG) + The levels were significantly reduced, demonstrating that TMG supports NAD. + Spermine synthesis plays a certain role in enhancing cellular energy metabolism (ATP production). The ATP level in control group 7 (without spermine) also decreased. Combined with the weakened lifespan-extending effect, this suggests that spermine may indirectly optimize overall mitochondrial function by promoting autophagy to clear dysfunctional mitochondria, thereby supporting stable ATP production.

[0069] The low ATP levels in Comparative Examples 2 and 5 directly demonstrate that the bilayer formulation of this invention is indispensable for ensuring the absorption and utilization of active ingredients, thereby achieving the best biological effects.

[0070] The examples and comparative data together demonstrate that the absence of any of the core features of the present invention will result in a decrease in the stability or final effect of the product.

[0071] The above description is merely a preferred embodiment of the present invention and is not intended to limit the present invention in any way. Although the present invention has been disclosed above with reference to preferred embodiments, it is not intended to limit the present invention. Any person skilled in the art can make some modifications or alterations to the above-disclosed technical content to create equivalent embodiments without departing from the scope of the present invention. Any simple modifications, equivalent changes and alterations made to the above embodiments based on the technical essence of the present invention without departing from the scope of the present invention shall still fall within the scope of the present invention.

Claims

1. An anti-aging composition, characterized in that, The composition comprises microcapsules assembled from a water-soluble wall material, a first core material, a fat-soluble wall material, and a second core material, sequentially coated from the outside to the inside, wherein: The raw materials of the first core material include β-nicotinamide mononucleotide (NMN), nicotinamide ribose (NR), ergothioneine and trimethylglycine (TMG), and the first core material is formed from a dispersion of its raw materials; The raw materials for the second core material include liposomed resveratrol, liposomed curcumin, pyrroloquinoline quinone and spermidine, and the second core material is formed by an oily dispersion of its raw materials dissolved in MCT oil.

2. The anti-aging composition according to claim 1, characterized in that, Based on a single capsule, the raw materials of the first core material include: NMN 250-500 mg, NR 100-300 mg, ergothioneine 5-10 mg, and TMG 5-20 mg.

3. The anti-aging composition according to claim 2, characterized in that, Based on a single capsule, the raw materials of the first core material include: NMN 300 mg, NR 100 mg, ergothioneine 8 mg, and TMG 10 mg.

4. The anti-aging composition according to claim 1, characterized in that, Based on a single capsule, the raw materials of the second core material include: 20-30 mg of resveratrol, 40-60 mg of curcumin, 10-20 mg of PQQ, and 0.5-2 mg of spermidine.

5. The anti-aging composition according to claim 4, characterized in that, Based on a single capsule, the raw materials of the second core material include: 25 mg of resveratrol, 50 mg of curcumin, 15 mg of PQQ, and 1 mg of spermidine.

6. The anti-aging composition according to claim 1, characterized in that, The raw materials for the second core material also include tocopherol at a weight of 0.05%-0.2% of the MCT oil.

7. The anti-aging composition according to claim 1, characterized in that, The water-soluble wall material is hydroxypropyl methylcellulose (HPMC); the fat-soluble wall material is gelatin.

8. A method for preparing an anti-aging composition according to any one of claims 1-7, characterized in that, Includes the following steps: (1) The second core material raw material and tocopherol are dissolved in MCT oil to form an oil phase, which is then encapsulated and shaped using a fat-soluble wall material to obtain the contents; (2) The capsule shell is made using a water-soluble wall material; (3) Place the pre-made contents into the lower half of the capsule, and then fill the surrounding cavity with the uniformly mixed first core material under the protection of inert gas. (4) Fit the capsule cap and lock it to complete the final sealing of the capsule.

9. The method according to claim 8, characterized in that, In step (1), the inert gas is nitrogen or argon.

10. The use of an anti-aging composition according to any one of claims 1-7 in the preparation of health products or pharmaceuticals for enhancing mitochondrial function to support cellular energy metabolism, delaying aging, or improving skin condition.

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