Anti-aging composition and use thereof, and Anti-aging capsule and use thereof

Abstract

The present invention relates to the technical field of anti-aging compositions and particularly to an anti-aging composition and use thereof, and an anti-aging capsule and use thereof. The present invention provides an anti-aging composition comprising the following components: 20-2000 parts by mass of calcium α-ketoglutarate, 20-100 parts by mass of quercetin, 20-2000 parts by mass of trans-resveratrol, 20-100 parts by mass of calendulin, and 0.02-1.8 parts by mass of spermidine. The composition of the present invention has a multi-target synergistic effect on 12 major causes of aging and can safely and effectively reverse aging, enhance the physiological function, reduce the risk of chronic diseases, and improve the quality of life. The components of the composition are safe, and are carefully selected natural food ingredients; therefore, the composition is safe and reliable, and has no side effects with long-term use. The composition is prepared in an oral dosage form, so that the composition is convenient to administer, which improves patient compliance; moreover, the mode of application of the composition can be expanded.

Description

An anti-aging composition and its application, and an anti-aging capsule and its application Technical Field

[0001] The present invention relates to the technical field of anti-aging compositions, in particular to an anti-aging composition and application thereof, and an anti-aging capsule and application thereof. Background Art

[0002] Aging is the strongest risk factor for most chronic diseases, physical and cognitive impairment, and mortality. Despite this, our approaches to understanding and treating age-related diseases often overlook the biological basis of the aging process. Aging science suggests that directly targeting aging itself has the potential to simultaneously slow the progression of multiple age-related diseases. As the global elderly population continues to grow, the prospect of treating aging to extend healthy lifespan is becoming increasingly promising. As the aging population intensifies, the health of the elderly population is receiving increasing attention.

[0003] However, aging is a complex physiological process involving multiple mechanisms. Currently, all 12 molecular mechanisms of aging have been identified (PMID: 36599349): altered intercellular communication, cellular aging, chronic inflammation, dysregulated nutrient sensing, impaired autophagy, dysbiosis, epigenetic changes, genomic instability, loss of proteostasis, mitochondrial dysfunction, stem cell depletion, and telomere attrition. These mechanisms represent common aging features across diverse organisms and species. Currently available anti-aging products often target only a single aging mechanism, lacking a comprehensive anti-aging approach. For example, low-calorie diets and young blood transfusions can partially reverse aging, but low-calorie diets are difficult to quantify, may cause digestive disorders (including anorexia) or psychological disorders, and are unnatural and difficult to adhere to. Young blood transfusions pose significant ethical challenges and carry inherent transfusion complications, such as hemolysis and the transmission of diseases. Therefore, the anti-aging field urgently needs new, comprehensive approaches to reverse aging.

[0004] Summary of the Invention

[0005] The purpose of the present invention is to provide an anti-aging composition that targets the 12 major causes of aging and has a multi-target synergistic effect. It can safely and effectively reverse aging, enhance physiological functions, reduce the risk of chronic diseases, and improve the quality of life.

[0006] In order to achieve the above-mentioned object of the invention, the present invention provides the following technical solutions:

[0007] The present invention provides an anti-aging composition, comprising the following components in parts by mass: 20 to 2000 parts of α-ketoglutarate calcium, 20 to 100 parts of quercetin, 20 to 2000 parts of trans-resveratrol, 20 to 100 parts of calendulin, and 0.02 to 1.8 parts of spermidine.

[0008] Preferably, the composition includes the following components in parts by mass: 20-2000 parts of calcium α-ketoglutarate, 20-100 parts of quercetin, 20-2000 parts of trans-resveratrol, 20-100 parts of calendula, 0.02-1.8 parts of spermidine, 20-2000 parts of glycine, 20-1200 parts of berberine, and 20-500 parts of urolithin A.

[0009] Preferably, the composition includes the following components in parts by mass: 20-2000 parts of calcium α-ketoglutarate, 20-100 parts of quercetin, 20-2000 parts of trans-resveratrol, 20-100 parts of calendula, 0.02-1.8 parts of spermidine, 20-2000 parts of glycine, 20-1200 parts of berberine, 20-500 parts of urolithin A, 0.1-1 part of trace lithium, 20-5400 parts of malic acid, 20-608 parts of magnesium, 1-200 parts of hyaluronic acid, 1-300 parts of L-theanine, 1-200 parts of vitamin C, 1-1800 parts of vitamin A, 1-50 parts of vitamin D, and 1-200 parts of 2% curcumin.

[0010] The present invention also provides the use of the composition in preparing anti-aging preparations.

[0011] Preferably, the anti-aging preparation is in the form of capsules, tablets, powders or injections.

[0012] The present invention also provides an anti-aging capsule, comprising a composition and excipients;

[0013] The composition is the composition described;

[0014] The mass ratio of the composition to the auxiliary materials is 5 to 9:1.

[0015] Preferably, the auxiliary materials include one or more of rice bran, hydroxypropyl methylcellulose, vegetable magnesium stearate, silicon dioxide, purple carrot, titanium dioxide, propylene glycol, polyvinyl acetate, benzoate, sodium lauryl sulfate and polyoxyethylene ether 80.

[0016] The invention also provides application of the capsule in anti-aging.

[0017] Beneficial effects of the present invention:

[0018] The anti-aging compounds of this invention achieve their effects of delaying and reversing aging through the following pathways: Genome protection: maintaining genomic stability and reducing DNA damage and mutations; Telomere extension: protecting telomere length and delaying cellular aging; Epigenetic regulation: optimizing gene expression and maintaining cellular function; Proteostasis maintenance: promoting the balance between protein synthesis and degradation and preventing protein aggregation; Autophagy enhancement: clearing damaged cellular components and maintaining cellular health; Optimizing nutrient sensing: regulating metabolic balance and delaying aging-related diseases; Enhanced mitochondrial function: improving energy production efficiency and reducing oxidative stress; Inhibiting cellular senescence: extending cell lifespan and maintaining tissue function; Activating stem cells: promoting tissue regeneration and repairing aging damage; Improving intercellular communication: coordinating cellular function and maintaining tissue integrity; Inhibiting inflammation: alleviating the damage to cells and tissues caused by chronic inflammation; Regulating the microbiome: maintaining a balanced intestinal flora and promoting overall health.

[0019] The composition of the present invention targets the 12 major causes of aging, with multi-target synergistic effects. It can reduce aging biomarkers (epigenetic age) in mammals, enhance the motor ability of mammals, improve metabolic disorders, restore the increase in liver epigenetic age caused by a high-fat diet, enhance memory ability, reduce skin wrinkles, and increase skin collagen content, thereby safely and effectively reversing aging, enhancing physiological functions, reducing the risk of chronic diseases, and improving quality of life. The composition has safe ingredients, carefully selected natural food ingredients, is safe and reliable, and has no side effects when taken long-term. The oral dosage form is convenient to take, easy to adhere to, and can expand its application methods. BRIEF DESCRIPTION OF THE DRAWINGS

[0020] Figure 1 shows the percentage of epigenetic age reduction in the normal diet group;

[0021] Figure 2 shows the percentage of epigenetic age reduction in the high-fat diet group;

[0022] Figure 3 shows the results of exercise capacity measurement, where Figure A shows the speed fold change and Figure B shows the endurance time fold change;

[0023] Figure 4 shows the improvement of glucose tolerance after a high-fat diet;

[0024] Figure 5 shows the Morris maze test results;

[0025] Figure 6 shows the test results of skin wrinkles and skin collagen content. DETAILED DESCRIPTION

[0026] The present invention provides an anti-aging composition comprising the following components in parts by weight: 20 to 2000 parts, preferably 520 to 1500 parts, and more preferably 1010 parts, of calcium α-ketoglutarate;

[0027] 20-100 parts of quercetin, preferably 50-70 parts, more preferably 60 parts;

[0028] 20 to 2000 parts of trans-resveratrol, preferably 520 to 1500 parts, more preferably 1010 parts;

[0029] 20-100 parts of calendula, preferably 50-70 parts, more preferably 60 parts;

[0030] The amount of spermidine is 0.02 to 1.8 parts, preferably 0.52 to 1.3 parts, and more preferably 0.91 parts.

[0031] In the present invention, calcium α-ketoglutarate can provide mitochondria with key metabolites for producing cellular energy, helping mitochondria to produce cellular energy and improving exercise capacity; quercetin can enhance the immune system's immunity and eliminate "zombie" aging cells and dysfunctional proteins; trans-resveratrol has the DNA genome repair function of activating sirtuins, which can maintain the stability of the genome and epigenome; calendula can eliminate "zombie" aging cells and enhance the body's immunity; spermidine has the effect of enhancing mitochondrial phagocytosis and mitochondrial function.

[0032] In the present invention, the following components are included in parts by mass: 20 to 2000 parts of calcium α-ketoglutarate, preferably 520 to 1500 parts, more preferably 1010 parts;

[0033] 20-100 parts of quercetin, preferably 50-70 parts, more preferably 60 parts;

[0034] 20 to 2000 parts of trans-resveratrol, preferably 520 to 1500 parts, more preferably 1010 parts;

[0035] 20-100 parts of calendula, preferably 50-70 parts, more preferably 60 parts;

[0036] 0.02 to 1.8 parts of spermidine, preferably 0.52 to 1.3 parts, more preferably 0.91 parts;

[0037] 20 to 2000 parts of glycine, preferably 520 to 1500 parts, more preferably 1010 parts;

[0038] 20-1200 parts of berberine, preferably 420-800 parts, more preferably 610 parts;

[0039] Urolithin A is 20 to 500 parts, preferably 220 to 300 parts, and more preferably 260 parts.

[0040] In the present invention, glycine has the effect of extending the lifespan of mammals, which is similar to the effect of "methionine-restricted diet" (i.e., extending the lifespan of mammals) and enhancing mitochondrial autophagy ability; berberine can strongly activate the AMPK signal that promotes longevity and maintain blood sugar and metabolic balance; urolithin A has the effects of enhancing mitochondrial autophagy and enhancing muscle function.

[0041] In the present invention, the following components are included in parts by mass: 20 to 2000 parts of calcium α-ketoglutarate, preferably 520 to 1500 parts, more preferably 1010 parts;

[0042] 20-100 parts of quercetin, preferably 50-70 parts, more preferably 60 parts;

[0043] 20 to 2000 parts of trans-resveratrol, preferably 520 to 1500 parts, more preferably 1010 parts;

[0044] 20-100 parts of calendula, preferably 50-70 parts, more preferably 60 parts;

[0045] 0.02 to 1.8 parts of spermidine, preferably 0.52 to 1.3 parts, more preferably 0.91 parts;

[0046] 20 to 2000 parts of glycine, preferably 520 to 1500 parts, more preferably 1010 parts;

[0047] 20-1200 parts of berberine, preferably 420-800 parts, more preferably 610 parts;

[0048] 20 to 500 parts of urolithin A, preferably 220 to 300 parts, more preferably 260 parts,

[0049] A trace amount of lithium 0.1 to 1 part, preferably 0.5 to 0.6 part, more preferably 0.55 part;

[0050] 20 to 5400 parts of malic acid, preferably 2020 to 3400 parts, more preferably 2710 parts;

[0051] 20 to 608 parts of magnesium, preferably 220 to 408 parts, more preferably 314 parts;

[0052] 1-200 parts of hyaluronic acid, preferably 51-150 parts, more preferably 100.5 parts;

[0053] 1 to 300 parts of L-theanine, preferably 101 to 200 parts, more preferably 150.5 parts;

[0054] 1-200 parts of vitamin C, preferably 51-150 parts, more preferably 100.5 parts;

[0055] Vitamin A 1-1800 parts, preferably 801-1000 parts, more preferably 900.5 parts;

[0056] Vitamin D1-50 parts, preferably 21-30 parts, more preferably 25.5 parts;

[0057] 2% curcumin 1 to 200 parts, preferably 51 to 150 parts, more preferably 100.5 parts.

[0058] In the present invention, microdoses of lithium can extend the lifespan of various species, and supplementation with microdoses of lithium can promote healthy brain aging. Malic acid is a natural substance found in apples, and studies have shown that it can extend the lifespan of organisms. It can also help humans maintain healthy blood sugar levels. Magnesium supports healthy metabolism and targets inflammation at the cellular level. People who supplement with magnesium show less DNA damage. Malic acid and magnesium are often present together as magnesium malate. Studies have shown that acetylglucosamine, a component of hyaluronic acid, has been shown to extend the lifespan of animals, and oral intake of hyaluronic acid can reduce the appearance of wrinkles. Theanine is one of the substances responsible for the health effects of green tea. Theanine can extend the lifespan of various organisms, increase the production of aging-protective proteins such as FOXO1 and antioxidant enzymes, and help the body manage cross-linking. Vitamin C helps maintain a healthy epigenome, especially when used in combination with α-ketoglutarate. Vitamin A and vitamin D help reduce the epigenetic age of men, especially when used in combination with α-ketoglutarate.

[0059] The present invention also provides the use of the composition in preparing anti-aging preparations.

[0060] In the present invention, the dosage form of the anti-aging preparation is capsule, tablet, powder or injection.

[0061] The present invention also provides an anti-aging capsule, comprising a composition and excipients;

[0062] The composition is the composition described;

[0063] The mass ratio of the composition to the auxiliary materials is 5 to 9:1, preferably 7:1.

[0064] In the present invention, the auxiliary materials include one or more of rice bran, hydroxypropyl methylcellulose, vegetable magnesium stearate, silicon dioxide, purple carrot, titanium dioxide, propylene glycol, polyvinyl acetate, benzoate, sodium lauryl sulfate and polyoxyethylene ether 80.

[0065] In the present invention, if the auxiliary materials used are rice bran, hydroxypropyl methylcellulose, vegetable magnesium stearate, silicon dioxide, purple carrot, titanium dioxide, propylene glycol, polyvinyl acetate, benzoate, sodium lauryl sulfate and polyoxyethylene ether 80 in a weight ratio, the mass ratio of rice bran, hydroxypropyl methylcellulose, vegetable magnesium stearate, silicon dioxide, purple carrot, titanium dioxide, propylene glycol, polyvinyl acetate, benzoate, sodium lauryl sulfate and polyoxyethylene ether 80 is 2 to 60:2. 0~92:1~10:0.2~1:1~4:0.2~1:2~15:1~8:1~8:1~10:2.5~7, preferably 22~40:40~72:4~7:0.5~0.7:2~3:0.5~0.7:7~10:3~6:3~6:4~7:3.5~6, more preferably 31:56:5.5:0.6:2.5:0.6:8.5:4.5:4.5:5.5:4.75.

[0066] The invention also provides application of the capsule in anti-aging.

[0067] The technical solutions provided by the present invention are described in detail below with reference to the embodiments, but they should not be construed as limiting the scope of protection of the present invention.

[0068] Example 1 An anti-aging capsule

[0069] (1) Weighing a composition: Weighing 1000 mg of calcium α-ketoglutarate, 100 mg of quercetin, 500 mg of trans-resveratrol, 100 mg of calendulin, and 900 μg of spermidine, and mixing them to prepare a composition;

[0070] (2) Weighing and mixing the following excipients: 90 mg rice bran, 540 mg hydroxypropyl methylcellulose, 45 mg vegetable magnesium stearate, 4.5 mg silicon dioxide, 18 mg purple carrot, 4.5 mg titanium dioxide, 18 mg propylene glycol, 45 mg polyvinyl acetate, 45 mg benzoate, 45 mg sodium lauryl sulfate, and 45 mg polyoxyethylene ether 80 to prepare an excipient;

[0071] (3) Preparation of capsules: The above composition and excipients were mixed in a ratio of 9:1, and anti-aging capsules were prepared automatically in a GMP environment; a single capsule cap was 11.50 mm long, a single wall was 0.090 mm thick, and an external diameter was 8.45 mm; a capsule body was 20.00 mm long, a single wall was 0.090 mm thick, and an external diameter was 8.10 mm, containing 900 mg of total active ingredient.

[0072] Example 2: An anti-aging capsule

[0073] (1) Weighing a composition: Weighing 1000 mg of calcium α-ketoglutarate, 100 mg of quercetin, 500 mg of trans-resveratrol, 100 mg of calendula, 900 μg of spermidine, 1000 mg of glycine, 600 mg of berberine, and 250 mg of urolithin A, and mixing them to prepare a composition;

[0074] (2) Weigh the auxiliary material reference example 1;

[0075] (3) Preparation of capsules Refer to Example 1.

[0076] Example 3: An anti-aging capsule

[0077] (1) Weighing a composition: weighing 1000 mg of calcium α-ketoglutarate, 100 mg of quercetin, 500 mg of trans-resveratrol, 100 mg of calendulin, 900 μg of spermidine, 1000 mg of glycine, 600 mg of berberine, 250 mg of urolithin A, 0.5 mg of trace lithium, 2700 mg of malic acid, 302 mg of magnesium, 100 mg of hyaluronic acid, 150 mg of L-theanine, 100 mg of vitamin C, 900 mg of vitamin A, 25 mg of vitamin D, and 100 mg of 2% curcumin, and mixing to prepare a composition;

[0078] (2) Weigh the auxiliary material reference example 1;

[0079] (3) Preparation of capsules Refer to Example 1.

[0080] Comparative Example 1: an anti-aging capsule

[0081] (1) Weighing a composition: Weigh 1000 mg of glycine, 600 mg of berberine, and 250 mg of urolithin A and mix to prepare a composition;

[0082] (2) Weigh the auxiliary material reference example 1;

[0083] (3) Preparation of capsules Reference Example 1

[0084] Experimental Example 1: Changes in Liver Epigenetic Age

[0085] Experimental mouse preparation: 68 male C57BL / 6J wild-type (WT) mice (4 months old, purchased from Jackson Lab) were selected and randomly divided into 17 treatment groups, as described in Table 1.

[0086] Table 1 Feeding methods of treatment groups

[0087] Note: The regular diet was LabDiet 5053, purchased from Labdiet; the high-fat Ain-93 diet was purchased from TestDiet and was formed by adding hydrogenated coconut oil to provide 60% of calories; the calorie diet was formed by gradually reducing 10% of food to the remaining 30% of food per week to form a 30% calorie diet; β-nicotinamide mononucleotide was purchased from Sigma.

[0088] All the drugs in the above treatment groups were administered to mice by gavage at 300 mg / kg once a day, and the feeding amount of feed was 5 g / day for each mouse, with free access to food.

[0089] After 10 months of feeding, mouse livers were collected and genomic DNA was extracted and purified using the DNeasy Blood and Tissue Kit (Qiagen) instructions. A corresponding RRBS methylation microarray library (Illumia) was constructed using a slightly modified method described in reference PMID 28380383. Methylation site profiles were determined using the Illumia RRBS methylation microarray. Methylation site profiles were determined using the following bioinformatics tools and algorithms (http: / / www.bioinformatics.babraham.ac.uk / projects / fastqc / , http: / / www.bioinformatics.babraham.ac.uk / projects / trim_galore / , http: / / www.bioinformatics.babraham.ac.uk / projects / bismark / ). Methylation data were entered into a specific epigenetic calculation website (https: / / dnamage.genetics.ucla.edu / home) and epigenetic age was calculated using the method described in reference PMID 38200273. The specific steps are as follows:

[0090] (1) Genomic DNA was extracted and purified according to the above kit. Sample processing: the tissue (25 mg mouse liver tissue) was cut into small pieces, placed in a 1.5 ml microcentrifuge tube, 180 μl Buffer ATL and 20 μl proteinase K were added, vortexed and incubated at 56°C until completely lysed; vortexed during the incubation process, vortexed for 15 seconds, 200 μl Buffer AL was added; vortexed and mixed evenly, the sample was incubated at 56°C overnight, 200 μl ethanol (96%) was added, vortexed and mixed evenly, the mixture was aspirated into a DNeasy Mini spin column placed in a 2 ml waste collection tube, centrifuged at 8000 rpm for 1 min, the effluent was discarded and the waste collection tube was reused, 500 μl Buffer AW1 was added, and centrifuged at 8000 rpm for 1 min, the effluent was discarded and the waste collection tube was reused, 500 μl Buffer AW2 and centrifuge at 14000 rpm for 3 minutes. Discard the effluent and waste collection tube and transfer to the purification column; transfer the spin column to a new 2 ml microcentrifuge tube, and then elute the DNA by adding 200 μl of Buffer AE to the center of the spin column membrane; incubate at 25°C for 1 minute and centrifuge at 8000 rpm for 1 minute to complete the extraction and purification of mouse liver genomic DNA;

[0091] (2) Establishment of RRBS library: First, genomic DNA restriction enzyme fragmentation, that is, after genomic DNA extraction, it is treated with restriction enzyme Msp I and then end-repair and adapter ligation, that is, after digestion of genomic DNA, the CG overhang at the 5' end is repaired and an A tail is added; secondly, genomic DNA fragmentation is followed by size selection: once adapter ligation is completed, DNA is loaded on an agarose gel, and fragments of 40-120 bp and 120-220 bp in length are separated and subjected to sulfite conversion;

[0092] (3) Sulfite conversion: Sulfite conversion deaminates non-methylated cytosine, converting it to a uracil residue, which is ultimately read as thymine in the analysis; methylated cytosine is protected from sulfite conversion and is therefore still read as cytosine in the analysis;

[0093] (4) PCR amplification: Before sequencing, sulfite-converted DNA was amplified by PCR;

[0094] (5) Sequencing: The amplified library was subjected to next-generation sequencing on the Illumina NGS platform;

[0095] (6) Obtaining the basication site profile through bioinformatics: After sequencing is completed, bioinformatics analysis is performed, including sequence alignment and methylation identification;

[0096] (7) The obtained methylation profile data were input into a public epigenetic age calculator (https: / / dnamage.genetics.ucla.edu / home) and the liver epigenetic age was calculated according to the method in reference PMID 38200273. The calculation results are shown in Figures 1 and 2.

[0097] As can be seen from Figure 1, Formula 1 and Formula 3 alone can reduce the epigenetic age of elderly people on a normal diet, Formula 2 can enhance the effect of Formula 1 in reducing the epigenetic age of elderly people on a normal diet, and the effect of Formula 2 alone is not obvious; the effect of Formula 1 + Formula 2 is better than that of Formula 3 alone (the anti-aging capsule described in Example 3), and none of the individual ingredients in Formula 1 + Formula 2 have the effect of reducing the epigenetic age of elderly people on a normal diet.

[0098] As shown in Figure 2, Formula 1 + Formula 2 can reverse the increase in epigenetic age caused by a high-fat diet; 30% caloric restriction can reduce epigenetic age, and Formula 1 + Formula 2 is more effective than Formula 3 in reducing epigenetic age compared to 30% caloric restriction. NMN is unable to reduce epigenetic age. Therefore, the anti-aging capsules described in Examples 1-3 can reduce the increase in genetic age caused by a high-fat diet.

[0099] Experimental Example 2: Exercise Ability Measurement Experiment

[0100] Preparation of experimental mice: 32 male C57BL / 6J wild-type (WT) mice (4 months old, purchased from Jackson Lab) were selected and randomly divided into 8 treatment groups: high-fat diet group (high-fat Ain-93 diet, purchased from TestDiet, formed by adding hydrogenated coconut oil to provide 60% of calories), 30% calories (a 30% calorie diet was formed by reducing food by 10% per week to the remaining 30% of food), high-fat diet group + Formulation 1 (Anti-aging capsules in Example 1), high-fat diet group Formula 2 (Anti-aging capsules in Comparative Example 2), high-fat diet group + Formulation 1 + Formulation 2 (Anti-aging capsules in Example 2), high-fat diet group + Formulation 3 (Anti-aging capsules described in Example 3), NMN (conventional feed + β-nicotinamide mononucleotide, purchased from Sigma), normal diet group (conventional feed); all the drugs in the above treatment groups were gavaged to mice at 300 mg / kg, once a day.

[0101] Exercise capacity was assessed using a motorized treadmill (Model 1050EXER 3 / 6; Columbus Instruments). Three days prior to testing, mice were acclimated to the treadmill by walking at 10 m / min for 10 minutes daily. At the start of testing, mice walked at 10 m / min, increasing their speed by 2 m / min every 2 minutes until endurance exhaustion. The time to endurance exhaustion and maximum speed were recorded. Testing began at 4 months of age and continued every 2 weeks for 6 months. The test results are shown in Figure 3, where Panel A shows the fold change in speed and Panel B shows the fold change in endurance time.

[0102] As shown in Figure 3, Formula 1 and Formula 3 alone can improve exercise capacity, namely, increasing maximum speed and endurance time. Formula 2 can enhance the effect of Formula 1 on exercise capacity. The effect of Formula 1 plus Formula 2 is superior to that of Formula 3. 30% caloric restriction can improve exercise capacity, while NMN cannot. Therefore, the anti-aging capsules described in Examples 1-3 can effectively improve exercise capacity.

[0103] Experimental Example 3 Glucose tolerance test

[0104] Preparation of experimental mice: 20 male C57BL / 6J wild-type (WT) mice (4 months old, purchased from Jackson Lab) were selected and randomly divided into 5 treatment groups: a normal diet group (fed with conventional feed without adding any drugs) served as the control group, and the following drugs were added to the mice fed a complete high-fat diet (high-fat Ain-93 diet, purchased from TestDiet, formed by adding hydrogenated coconut oil to provide 60% of calories): Formula 1 (the anti-aging capsule described in Example 1), Formula 2 (the anti-aging capsule described in Comparative Example 1), Formula 1+Formula 2 (the anti-aging capsule of Example 2), and Formula 3 (the anti-aging capsule of Example 3). The drugs in all the above treatment groups were gavaged to the mice at 300 mg / kg, once a day.

[0105] After 10 months of feeding, the mice were fasted for 12 hours and intraperitoneally injected with glucose (Sigma-Aldrich) at a dose of 2 g / kg per mouse. Blood samples were collected at 0, 15, 30, 60, and 120 minutes after injection, and serum insulin concentrations were measured using the UltraSensitive Mouse Insulin ELISA kit (Crystal Chem, 90080). The measurement results are shown in Figure 4.

[0106] As shown in Figure 4, Formula 1 plus Formula 2 can improve glucose tolerance after a high-fat diet, while Formula 1, Formula 2, Formula 3 alone, or a normal diet alone cannot improve glucose tolerance after a high-fat diet. This indicates that the anti-aging capsules described in Examples 1-3 can improve impaired glucose tolerance after a high-fat diet and treat metabolic disorders in mice fed a high-fat diet.

[0107] Experimental Example 4 Morris water maze test

[0108] Preparation of experimental mice: 20 male C57BL / 6J wild-type (WT) mice (4 months old, purchased from Jackson Lab) were selected and randomly divided into 5 treatment groups: a normal diet group (fed with conventional feed without adding any drugs), and the following drugs were added to the conventional feed: Formula 1 (the anti-aging capsule described in Example 1), Formula 2 (the anti-aging capsule described in Comparative Example 1), Formula 1+Formula 2 (the anti-aging capsule of Example 2), and Formula 3 (the anti-aging capsule of Example 3). The drugs in all the above treatment groups were gavaged to the mice at 300 mg / kg, once a day.

[0109] The Morris water maze (purchased from ConductScience) has a diameter of 90 cm and a height of 45 cm. The interior walls are painted black and filled with tap water maintained at 23°C. The escape platform, 6 cm in diameter and 24 cm high, is located in the center of the fourth quadrant of the maze, 1 cm below the water surface. A camera is mounted directly above the water maze and connected to the device analysis system for image and data acquisition. The water maze is divided into four quadrants: Q1, Q2, Q3, and Q4. Q3 is the target quadrant and contains the escape platform Q5. The experiment was divided into two phases: training and testing. During the training phase, mice were randomly placed in the water in one of the four quadrants. Software recorded the time it took for the mouse to enter the water and climb onto the platform, which is known as the escape latency. Each mouse underwent four training sessions daily (entering the water from a different quadrant), with each session recorded for 1 minute, for 5 consecutive days. If the mouse failed to find the platform within 1 minute, it was manually guided to the platform and allowed to rest for 1 minute. During the testing phase, all mice were placed in water from a fixed quadrant (except the target quadrant). The software recorded for 1 minute and observed their process of searching for a safe platform. The escape latency (s) was the terminal observation indicator. The test results are shown in Figure 5.

[0110] As shown in Figure 5, Formula 1 + Formula 2, Formula 1 alone, and Formula 3 alone can improve memory ability. Formula 2 can enhance the memory-enhancing effect of Formula 1, while the effect of Formula 2 alone is not significant. Formula 1 + Formula 2 is more effective than Formula 3. Therefore, the anti-aging capsules described in Examples 1-3 can improve memory ability.

[0111] Experimental Example 5

[0112] Preparation of experimental mice: 24 male C57BL / 6J wild-type (WT) mice (4 weeks old, purchased from Jackson Lab) were selected and randomly divided into 6 treatment groups: 4-week-old mice fed a normal diet served as blank controls; the experimental groups were: a normal diet group (fed with conventional feed without adding any drugs), and the following drugs were added to the conventional feed: Formula 1 (the anti-aging capsule described in Example 1), Formula 2 (the anti-aging capsule described in Comparative Example 1), Formula 1+Formula 2 (the anti-aging capsule of Example 2), and Formula 3 (the anti-aging capsule of Example 3). The drugs in the above experimental groups were all gavaged to the mice at 300 mg / kg, once a day, and fed for 10 months.

[0113] Wrinkles on the backs of 4-week-old nude mice fed a normal diet and the experimental group after 10 months of feeding were detected and photographed, and the wrinkles were quantified by inputting into NIH Imagine J software; at the same time, the corresponding full-thickness skin of the nude mice was removed and fixed with 4% paraformaldehyde; the fixed skin tissue was gradually dehydrated in ethanol solutions of different concentrations, usually starting from a low concentration of ethanol (70%) and gradually transferred to a higher concentration of ethanol (100%), and the dehydrated skin tissue was placed in an appropriate organic solvent (pentanol) to remove fat and make the tissue transparent; the skin tissue after fat removal was placed in liquid paraffin or molten wax for immersion, and the wax was solidified at low temperature, and the solidified skin tissue was cut using a rotary tissue slicer (Thermo Fisher) to obtain slices (thickness of 10 μm), which were placed in a staining box and stained with the dye Masson's Trichrome (lab Vector) to specifically stain collagen fibers; the stained slices were washed under running water to remove excess dye and then sealed, photographed with a microscope (Leica) and input into the U.S. NIH Imagine J software was used to calculate the skin collagen content. The wrinkle gross observation score and the change in collagen III absorption fold are shown in Figure 6.

[0114] The standard reference for gross wrinkle observation scoring (PMID: 2169296) is as follows: 0 points: normal skin with fine texture; 1 point: fine scratches on the skin; 2 points: a few shallow wrinkles; 3 points: more shallow wrinkles; 4 points: rough skin with deep wrinkles; 5 points: more rough wrinkles; 6 points: rough wrinkles and local skin damage.

[0115] As shown in Figure 6, Formula 1 + Formula 2, Formula 1 alone, and Formula 3 alone can reduce skin wrinkles and increase collagen III content. Formula 2 can enhance the effect of Formula 1, while the effect of Formula 2 alone is not significant. Formula 1 + Formula 2 is more effective than Formula 3. Therefore, the anti-aging capsules described in Examples 1-3 can effectively reduce skin wrinkles and increase skin collagen content.

[0116] Example 4: An anti-aging capsule

[0117] (1) Weighing a composition: Weighing 1200 mg of calcium α-ketoglutarate, 80 mg of quercetin, 1000 mg of trans-resveratrol, 50 mg of calendulin, and 1000 μg of spermidine, and mixing to prepare a composition;

[0118] (2) Weighing and mixing the following excipients: 360 mg rice bran, 675 mg hydroxypropyl methylcellulose, 90 mg vegetable magnesium stearate, 15 mg silicon dioxide, 45 mg purple carrot, 15 mg titanium dioxide, 45 mg propylene glycol, 90 mg polyvinyl acetate, 60 mg benzoate, 60 mg sodium lauryl sulfate, and 45 mg polyoxyethylene ether 80 to prepare an excipient;

[0119] (3) Preparation of capsules: The above composition and excipients were mixed in a ratio of 7:1 and anti-aging capsules were prepared in a fully automatic manner in a GMP environment; a single capsule cap was 11.50 mm long, a single wall was 0.090 mm thick, and an external diameter was 8.45 mm; a capsule body was 20.00 mm long, a single wall was 0.090 mm thick, and an external diameter was 8.10 mm, containing 900 mg of total active ingredient.

[0120] Example 5: An anti-aging capsule

[0121] (1) Weighing a composition: Weighing 1200 mg of calcium α-ketoglutarate, 80 mg of quercetin, 1000 mg of trans-resveratrol, 50 mg of calendula, 1000 μg of spermidine, 1500 mg of glycine, 1000 mg of berberine, and 400 mg of urolithin A, and mixing to prepare a composition;

[0122] (2) Weigh the auxiliary material reference example 4;

[0123] (3) Preparation of capsules Refer to Example 4.

[0124] Example 6: An anti-aging capsule

[0125] (1) Weighing a composition: weighing 1200 mg of calcium α-ketoglutarate, 80 mg of quercetin, 1000 mg of trans-resveratrol, 50 mg of calendulin, 1000 μg of spermidine, 1500 mg of glycine, 1000 mg of berberine, 400 mg of urolithin A, 1 mg of trace lithium, 3000 mg of malic acid, 600 mg of magnesium, 150 mg of hyaluronic acid, 200 mg of L-theanine, 50 mg of vitamin C, 700 mg of vitamin A, 40 mg of vitamin D, and 150 mg of 2% curcumin, and mixing to prepare a composition;

[0126] (2) Weigh the auxiliary material reference example 4;

[0127] (3) Preparation of capsules Refer to Example 4.

[0128] As can be seen from the above embodiments, the present invention provides an anti-aging composition and its application, and an anti-aging capsule and its application. The composition targets the 12 major causes of aging, and has a multi-target synergistic effect, which can safely and effectively reverse aging, enhance physiological functions, reduce the risk of chronic diseases, and improve the quality of life. The composition has safe ingredients, selected natural food ingredients, is safe and reliable, and has no side effects when taken for a long time. The oral dosage form is convenient to take, easy to adhere to, and can expand its application methods.

[0129] The above is only a preferred embodiment of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the principles of the present invention. These improvements and modifications should also be regarded as within the scope of protection of the present invention.

Claims

1. An anti-aging composition, characterized in that: The invention comprises the following components in parts by mass: 20 to 2000 parts of α-ketoglutarate calcium, 20 to 100 parts of quercetin, 20 to 2000 parts of trans-resveratrol, 20 to 100 parts of calendula, and 0.02 to 1.8 parts of spermidine.

2. The composition according to claim 1, characterized in that The invention comprises the following components in parts by mass: 20 to 2000 parts of α-ketoglutarate calcium, 20 to 100 parts of quercetin, 20 to 2000 parts of trans-resveratrol, 20 to 100 parts of calendula, 0.02 to 1.8 parts of spermidine, 20 to 2000 parts of glycine, 20 to 1200 parts of berberine and 20 to 500 parts of urolithin A.

3. The composition according to claim 2, characterized in that The invention comprises the following components in parts by mass: 20-2000 parts of α-ketoglutarate calcium, 20-100 parts of quercetin, 20-2000 parts of trans-resveratrol, 20-100 parts of calendula, 0.02-1.8 parts of spermidine, 20-2000 parts of glycine, 20-1200 parts of berberine, 20-500 parts of urolithin A, 0.1-1 part of trace lithium, 20-5400 parts of malic acid, 20-608 parts of magnesium, 1-200 parts of hyaluronic acid, 1-300 parts of L-theanine, 1-200 parts of vitamin C, 1-1800 parts of vitamin A, 1-50 parts of vitamin D, and 1-200 parts of 2% curcumin.

4. Use of the composition according to any one of claims 1 to 3 in the preparation of anti-aging preparations.

5. The use according to claim 4, characterized in that The dosage form of the anti-aging preparation is capsule, tablet, powder or injection.

6. An anti-aging capsule, characterized in that: including compositions and excipients; The composition is the composition according to any one of claims 1 to 3; The mass ratio of the composition to the auxiliary materials is 5 to 9:

1.

7. The capsule according to claim 6, characterized in that The auxiliary materials include one or more of rice bran, hydroxypropyl methylcellulose, vegetable magnesium stearate, silicon dioxide, purple carrot, titanium dioxide, propylene glycol, polyvinyl acetate, benzoate, sodium lauryl sulfate and polyoxyethylene ether 80.

8. Use of the capsule according to claim 6 or 7 in anti-aging.

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