阅读说明：本技术 一种延缓衰老的含核苷酸的组合物及其制备方法和应用 (Composition containing nucleotide for delaying senescence and preparation method and application thereof ) 是由 陈玉松 于 2021-07-30 设计创作，主要内容包括：本发明公开一种延缓衰老的含核苷酸组合物,属于医药保健技术领域,本发明的含核苷酸组合物包括AMP、CMP、GMP、UMP按照一定配比的复配核苷酸和茶多酚、黄芪多糖、姜黄素、白藜芦醇、海洋鱼低聚肽、辅酶Q10、烟酰胺等功能活性成分,本发明所述的延缓衰老的含核苷酸组合物能够清除体内自由基进而抗氧化,对损伤细胞具有保护和修复作用,延缓机体衰老,协同发挥其抗衰老功效。(The invention discloses a nucleotide-containing composition for delaying senescence, which belongs to the technical field of medicine and health care, and comprises AMP, CMP, GMP and UMP which are compounded according to a certain proportion, tea polyphenol, astragalus polysaccharide, curcumin, resveratrol, marine fish oligopeptide, coenzyme Q10, nicotinamide and other functional active ingredients.)

1. The composition containing the nucleotide for delaying the aging is characterized by being prepared by compounding the nucleotide and functional active ingredients according to a certain proportion, wherein the compound nucleotide consists of AMP, CMP, GMP and UMP; the functional active ingredient is one or more of tea polyphenol, astragalus polysaccharide, curcumin, resveratrol, marine fish oligopeptide, coenzyme Q10 and nicotinamide.

2. The nucleotide-containing composition according to claim 1, wherein the weight ratio of the compound nucleotide is: 15.0-25.0% of AMP, 15.0-45.0% of CMP, 15.0-35.0% of GMP and 15.0-30.0% of UMP, wherein the weight ratio of the compound nucleotide to the functional active ingredients is as follows: 0.5-1.5 parts of compound nucleotide, 0.5-2 parts of tea polyphenol, 0.02-0.1 part of resveratrol, 100.02-0.08 part of coenzyme Q and 0.01-0.04 part of nicotinamide; or 0.5-1.5 parts of compound nucleotide, 0.1-0.4 part of astragalus polysaccharide, 0.1-0.4 part of curcumin, 0.02-0.1 part of resveratrol and 0.01-0.04 part of nicotinamide; or 0.5-1.5 parts of compound nucleotide and 0.2-0.8 part of marine fish oligopeptide.

3. The nucleotide-containing composition according to claims 1-2, wherein the weight ratio of the compound nucleotide is: AMP 16.9%, CMP 43.2%, GMP 17.8% and UMP 22.1%, wherein the weight ratio of the compound nucleotide to the functional active ingredients is as follows: 1.2 parts of compound nucleotide, 1 part of tea polyphenol, 0.05 part of resveratrol, 100.04 parts of coenzyme Q and 0.02 part of nicotinamide.

4. The nucleotide-containing composition according to claims 1-2, wherein the weight ratio of the compound nucleotide is: AMP 16.9%, CMP 43.2%, GMP 17.8% and UMP 22.1%, wherein the weight ratio of the compound nucleotide to the functional active ingredients is as follows: 1.2 parts of compound nucleotide, 0.2 part of astragalus polysaccharide, 0.19 part of curcumin, 0.05 part of resveratrol and 0.02 part of nicotinamide.

5. The nucleotide-containing composition of claims 1-2, wherein the weight ratio of the compounded nucleotide is: AMP 24.3%, CMP 28.3%, GMP 19.3%, UMP 28.1%, the weight ratio of the compound nucleotide and the functional active ingredients is: 0.6 part of compound nucleotide and 0.43 part of marine fish oligopeptide.

6. The nucleotide-containing composition of claim 3, 4, or 5, wherein the composition is in a finished state comprising a powder, a granule, a tablet, a pill, an oral liquid, a capsule.

7. The method for preparing the nucleotide-containing composition according to any one of claims 1 to 6, wherein the compound nucleotide is weighed according to the proportion, the compound nucleotide is uniformly mixed to obtain mixed powder, and the mixed powder and the functional active ingredient with the formula amount are uniformly mixed to obtain the nucleotide-containing composition.

8. Use of the nucleotide-containing composition of any one of claims 1-6 for the preparation of a pharmaceutical, nutraceutical, or functional food.

9. The use according to claim 8, wherein the nucleotide-containing composition is added to a pharmaceutical, nutraceutical or functional food product, either directly or after treatment with conventional procedures.

10. The use according to claim 9, wherein the pharmaceutical, nutraceutical or functional food has effects of scavenging free radicals in vivo, resisting oxidation, protecting and repairing damaged cells, and delaying aging.

Technical Field

The invention belongs to the technical field of medicine and health care, and particularly relates to a nucleotide-containing composition with an aging delaying function, and a preparation method and application thereof.

Background

The aging of human body is actually the aging of human cells, and after about 40-60 divisions, the cells die and can not continue to divide. The decrease in cellular activity and ability to divide is a real cause of body senescence. To delay aging, the vitality and vitality of the cells of the body must be increased. The cell is composed of cell membrane, cell sap and cell nucleus. The nucleus of a cell harbors a gene, a basic life code. A gene is the entire nucleotide sequence required to produce a polypeptide chain or functional RNA.

Nucleic acid is a biological macromolecular compound formed by polymerizing a plurality of nucleotides, and is one of the most basic substances of life. Nucleic acids are widely present in all animals, plant cells, microorganisms. Nucleic acids are classified into deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) according to their chemical composition. DNA is the primary material basis for the storage, replication, and transmission of genetic information, and RNA plays an important role in the protein synthesis process. Three types of RNA are involved in protein synthesis, transfer RNA (tRNA), messenger RNA (mRNA), and ribosomal RNA (rRNA). tRNA is used to carry and transfer active amino acid; mRNA is a template for synthetic proteins; rRNA is the major site of protein synthesis by cells. Nucleic acids not only are essential genetic materials but also occupy important positions in protein biosynthesis and thus play a crucial role in a series of vital phenomena such as growth, inheritance, and mutation. A nucleic acid is a polynucleotide whose basic structural unit is a nucleotide.

Nucleotides are basic constitutional units of ribonucleic acid and deoxyribonucleic acid, and are distributed in the nucleus and cytoplasm of each organ, tissue and cell in an organism as nucleic acids, and participate in basic life activities such as heredity, development and growth of the organism as a constitutional component of the nucleic acids. Nucleotide compounds have important biological functions, and participate in almost all biochemical reaction processes in organisms: the nucleotide is a precursor for synthesizing biomacromolecule ribonucleic acid and deoxyribonucleic acid; adenosine Triphosphate (ATP) plays an extremely important role in cellular energy metabolism; ATP can also transfer high-energy phosphate bonds to UDP, CDP and GDP to generate UTP, CTP and GTP; adenosine is also a component of several important coenzymes, such as coenzyme I (nicotinamide adenine dinucleotide, NAD +), coenzyme II (nicotinamide adenine dinucleotide phosphate, NADP +), Flavin Adenine Dinucleotide (FAD) and coenzyme A (CoA); nucleotides have a regulatory role in many basic biological processes. In the last two decades, exogenous nucleotides have been widely used in infant formula milk powder and health care products, and the safety of the exogenous nucleotides used in human bodies has been fully proved by scientific experiments. Patent (CN104771330A) discloses a composition containing nicotinamide mononucleotide for anti-aging, beautifying and skin caring, which applies nicotinamide mononucleotide as an active ingredient in the anti-aging, beautifying and skin caring composition, and can prevent skin roughness and aging, reduce skin wrinkles, and keep skin bright and elastic. However, no related research on a composition which is safe and effective, has no toxic or side effect and synergistically delays the aging of organisms and is obtained by combining nucleotide and functional active ingredients has been reported.

Disclosure of Invention

In view of the above, the invention aims to provide a composition containing nucleotides for delaying aging, which is a composition consisting of four mononucleotides of AMP, CMP, GMP and UMP, and functional active ingredients such as tea polyphenol, astragalus polysaccharide, curcumin, resveratrol, marine fish oligopeptide, coenzyme Q10 and nicotinamide according to a certain proportion, wherein the obtained finished product has the effects of delaying aging of organisms and enhancing the vitality of cells.

In order to achieve the purpose, the invention is realized by the following technical scheme:

a composition containing nucleotide for delaying senility is prepared from compound nucleotide and functional active component through proportional mixing, and serves to delay senility, improve senility and prevent senility.

Further, based on the technical scheme, the compound nucleotide consists of AMP, CMP, GMP and UMP; the functional active ingredient is one or more of tea polyphenol, astragalus polysaccharide, curcumin, resveratrol, marine fish oligopeptide, coenzyme Q10 and nicotinamide.

Further, based on the technical scheme, the weight ratio of the compound nucleotide is as follows: 15.0-25.0% of AMP, 15.0-45.0% of CMP, 15.0-35.0% of GMP and 15.0-30.0% of UMP, wherein the weight ratio of the compound nucleotide to the functional active ingredients is as follows: 0.5-1.5 parts of compound nucleotide, 0.5-2 parts of tea polyphenol, 0.02-0.1 part of resveratrol, 100.02-0.08 part of coenzyme Q and 0.01-0.04 part of nicotinamide; or 0.5-1.5 parts of compound nucleotide, 0.1-0.4 part of astragalus polysaccharide, 0.1-0.4 part of curcumin, 0.02-0.1 part of resveratrol and 0.01-0.04 part of nicotinamide; or 0.5-1.5 parts of compound nucleotide and 0.2-0.8 part of marine fish oligopeptide.

Further, based on the technical scheme, the weight ratio of the compound nucleotide is as follows: the weight ratio of the compound nucleotide is as follows: AMP 16.9%, CMP 43.2%, GMP 17.8% and UMP 22.1%, wherein the weight ratio of the compound nucleotide to the functional active ingredients is as follows: 1.2 parts of compound nucleotide, 1 part of tea polyphenol, 0.05 part of resveratrol, 100.04 parts of coenzyme Q and 0.02 part of nicotinamide.

Further, based on the technical scheme, the weight ratio of the compound nucleotide is as follows: AMP 16.9%, CMP 43.2%, GMP 17.8% and UMP 22.1%, wherein the weight ratio of the compound nucleotide to the functional active ingredients is as follows: 1.2 parts of compound nucleotide, 0.2 part of astragalus polysaccharide, 0.19 part of curcumin, 0.05 part of resveratrol and 0.02 part of nicotinamide.

Further, based on the technical scheme, the weight ratio of the compound nucleotide is as follows: AMP 24.3%, CMP 28.3%, GMP 19.3%, UMP 28.1%, the weight ratio of the compound nucleotide and the functional active ingredients is: 0.6 part of compound nucleotide and 0.43 part of marine fish oligopeptide.

Further, based on the technical scheme, the finished product state of the composition comprises powder, granules, tablets, pills, oral liquid and capsules.

The invention also provides a preparation method of the nucleotide-containing composition, which comprises the steps of weighing the compound nucleotide according to the proportion, uniformly mixing to obtain mixed powder, and uniformly mixing the mixed powder and the functional active ingredients according to the formula amount to obtain the nucleotide-containing composition.

The invention also provides the application of the nucleotide-containing composition in preparing medicines, health-care products or functional foods.

Further, based on the above technical scheme, the nucleotide-containing composition is added into a medicine, a health product or a functional food directly or after being processed by conventional steps.

Further, based on the technical scheme, the medicine, the health-care product or the functional food has the effects of eliminating free radicals in vivo, resisting oxidation, well protecting and repairing damaged cells and delaying aging of organisms.

Compared with the prior art, the invention has the following beneficial effects:

the nucleotide-containing composition for delaying senescence provided by the invention is formed by matching four mononucleotides of AMP, CMP, GMP and UMP with various functional substances and vitamins, and has a synergistic effect, so that free radicals in vivo can be eliminated, oxidative damage of the free radicals to organisms is inhibited, the effect of delaying senescence can be achieved, and the organisms are full of young states.

Detailed Description

The present invention is further illustrated below by reference to specific examples, which are to be construed as merely illustrative, and not limitative of the remainder of the disclosure in any way whatsoever. In the following examples, unless otherwise specified, the experimental methods used were all conventional methods, and materials, reagents and the like used were all available from biological or chemical companies.

Example 1

Weighing raw materials of 16.9 percent of AMP, 43.2 percent of CMP, 17.8 percent of GMP and 22.1 percent of UMP in a clean area according to the weight ratio, uniformly mixing the raw materials by using a mixer to obtain powder, sampling according to the specification of a quality standard to carry out the inspection of each index, and keeping the powder for later use after the inspection is qualified; then weighing the raw materials in a clean area according to the proportion of 1.2 parts of the prepared compound nucleotide, 1 part of tea polyphenol, 0.05 part of resveratrol, 100.04 parts of coenzyme Q and 0.02 part of nicotinamide, uniformly mixing the raw materials by a mixer, and pressing the mixture into tablets with the weight of 0.3 g. And sampling the finished product according to the specification of the quality standard to check each index, and storing for later use after the finished product is qualified.

Example 2

Weighing raw materials of 16.9 percent of AMP, 43.2 percent of CMP, 17.8 percent of GMP and 22.1 percent of UMP in a clean area according to the weight ratio, uniformly mixing the raw materials by using a mixer to obtain powder, sampling according to the specification of a quality standard to carry out the inspection of each index, and keeping the powder for later use after the inspection is qualified; then weighing the raw materials in a clean area according to the proportion of 1.2 parts of the prepared compound nucleotide, 0.2 part of astragalus polysaccharide, 0.19 part of curcumin, 0.05 part of resveratrol and 0.02 part of nicotinamide, uniformly mixing the raw materials by using a mixer, and pressing the mixture into tablets with the weight of 0.3 g. And sampling the finished product according to the specification of the quality standard to check each index, and storing for later use after the finished product is qualified.

Example 3

Weighing raw materials of 24.3 percent of AMP, 28.3 percent of CMP, 19.3 percent of GMP and 28.1 percent of UMP in a clean area according to the weight ratio, uniformly mixing the raw materials by using a mixer to obtain powder, sampling according to the specification of a quality standard to carry out the inspection of each index, and keeping the powder for later use after the inspection is qualified; then weighing the raw materials in a clean area according to the proportion of 0.6 part of the prepared compound nucleotide and 0.43 part of the marine fish oligopeptide, uniformly mixing the raw materials by using a mixer, and pressing the mixture into tablets with the weight of 0.3 g. And sampling the finished product according to the specification of the quality standard to check each index, and storing for later use after the finished product is qualified.

Example 4

Weighing raw materials of 24.3 percent of AMP, 28.3 percent of CMP, 19.3 percent of GMP and 28.1 percent of UMP in a clean area according to the weight ratio, uniformly mixing the raw materials by using a mixer to obtain powder, sampling according to the specification of a quality standard to carry out the inspection of each index, and keeping the powder for later use after the inspection is qualified; then weighing the raw materials in a clean area according to the proportion of 1.2 parts of the prepared compound nucleotide, 1 part of tea polyphenol, 0.05 part of resveratrol, 100.04 parts of coenzyme Q and 0.02 part of nicotinamide, uniformly mixing the raw materials by a mixer, and pressing the mixture into tablets with the weight of 0.3 g. And sampling the finished product according to the specification of the quality standard to check each index, and storing for later use after the finished product is qualified.

Example 5

Weighing raw materials of 24.3 percent of AMP, 28.3 percent of CMP, 19.3 percent of GMP and 28.1 percent of UMP in a clean area according to the weight ratio, uniformly mixing the raw materials by using a mixer to obtain powder, sampling according to the specification of a quality standard to carry out the inspection of each index, and keeping the powder for later use after the inspection is qualified; then weighing the raw materials in a clean area according to the proportion of 1.2 parts of the prepared compound nucleotide, 0.2 part of astragalus polysaccharide, 0.19 part of curcumin, 0.05 part of resveratrol and 0.02 part of nicotinamide, uniformly mixing the raw materials by using a mixer, and pressing the mixture into tablets with the weight of 0.3 g. And sampling the finished product according to the specification of the quality standard to check each index, and storing for later use after the finished product is qualified.

Example 6

To verify the anti-aging effect of the nucleotide-containing composition of the present invention, the experiment was first conducted by examining the antioxidant properties of the nucleotide-containing composition.

1 tablet prepared in example 1 was weighed and dissolved in a mixed solution of deionized water and ethanol (volume ratio: 1) to prepare a mother liquor having a concentration of 1mg/mL, and DPPH radical clearance and ABTS radical clearance were measured.

Determination of DPPH radical scavenging Rate:

the mother liquor was diluted 100, 50, 25, 10, 1 fold to prepare gradient dilutions of 10. mu.g/mL, 20. mu.g/mL, 40. mu.g/mL, 100. mu.g/mL, 500. mu.g/mL, respectively.

Respectively placing the above 150 μ L sample and 150 μ L DPPH solution (diluted with anhydrous ethanol) with concentration of 60mg/L in 96-well plate, mixing, storing at 30 deg.C in dark place, and measuring absorbance value under 519nm with microplate reader after 30 min. The DPPH radical clearance equation is as follows:

in the formula, blank A is the absorbance of 150 mu L of deionized water ethanol solution and 150 mu L of DPPH solution, and sample A is the absorbance of 150 mu L of sample and 150 mu L of DPPH solution; IC (integrated circuit)₅₀The concentration of the sample at which DPPH free radical scavenging rate reached 50%.

Determination of ABTS free radical clearance:

(1) the mother liquor was diluted 100, 50, 25, 10, 1 fold to prepare gradient dilutions of 10. mu.g/mL, 20. mu.g/mL, 40. mu.g/mL, 100. mu.g/mL, 500. mu.g/mL, respectively.

(2) A solution of 7mmol/L ABTS and a solution of 140mmol/L potassium persulfate were mixed at a ratio of 62.5: 1, standing overnight at room temperature in the dark to form ABTS stock solution, and diluting with deionized water to obtain 5mmol/L ABTS working solution before use.

(3) 0.15mL of the above diluted solution sample was mixed with 2.85mL of ABTS working solution, and the mixture was left standing at 30 ℃ for 8min, and absorbance was measured at 734nm using deionized water as a blank.

The ABTS free radical clearance equation is as follows:

in the formula, blank A is the absorbance of 0.15mL of deionized water ethanol solution and 2.85mL of ABTS working solution, and sample A is the absorbance of 0.15mL of sample and 2.85mL of ABTS working solution. IC (integrated circuit)₅₀Is the concentration of the sample at which the ABTS free radical clearance reaches 50%.

The antioxidant performance of the tablets containing nucleotide composition in example 2 and the tablets containing nucleotide composition in example 3 were tested by referring to the same test method as above, using the compound nucleotide only in the same amount and the same ratio as the tablets in example 1 as control experiment 1, using the compound nucleotide only in the same amount and the same ratio as the tablets in example 3 as control experiment 2, using the composition of tea polyphenol, resveratrol, coenzyme Q10 and nicotinamide only in the same amount and the same ratio as the tablets in example 1 as control experiment 3, using the composition of astragalus polysaccharide, curcumin, resveratrol and nicotinamide only in the same amount and the same ratio as the tablets in example 2 as control experiment 4, using the marine fish oligopeptide only in the same amount and the same ratio as the tablets in example 3 as control experiment 5, wherein the test data are expressed by mean value + -standard deviation, the results of the experiment are shown in table 1.

TABLE 1 antioxidant Properties of nucleotide-containing compositions

The results show that compared with the control groups 1 to 5, the nucleotide-containing compositions of the examples 1 to 3 have higher antioxidant performance, the antioxidant performance is obviously enhanced after the compound nucleotide and the functional active ingredients are compounded, and the nucleotide-containing compositions of the examples 1 to 3 can more effectively remove free radicals of organisms.

Experimental example 7

In order to further verify that the nucleotide-containing composition of the present invention has the effect of delaying aging, in vitro experiments were performed for evaluation. Human umbilical vein endothelial cells and PC-12 cells (rat adrenal pheochromocytoma cells) are taken as models, and H is adopted₂O₂Modeling, evaluation experiments were conducted on the nucleotide-containing compositions of examples 1-3, using only the same amount and ratio of the formulated nucleotide as the tablets of example 1 as control experiment 1, using only the same amount and ratio of the formulated nucleotide as the tablets of example 3 as control experiment 2, and using only the same amount and ratio of the formulated nucleotide as the tablets of example 1 as control experiment 2The cytotoxicity test and the intracellular ROS level evaluation test were carried out by using the composition of phenol, resveratrol, coenzyme Q10 and nicotinamide as a control experiment 3, the composition of astragalus polysaccharide, curcumin, resveratrol and nicotinamide only in the same amount and the same ratio as the tablets in example 2 as a control experiment 4, the marine fish oligopeptide only in the same amount and the same ratio as the tablets in example 3 as a control experiment 5, and the beta-Nicotinamide Mononucleotide (NMN) in the same dosage as a control experiment 6.

1. Cytotoxicity assays

Digesting the cells in logarithmic growth phase into single cell suspension, and regulating cell concentration to 10⁵one/mL, seeded in 96-well cell culture plates at 100 μ L per well, 6 parallel wells per group. 24 hours after inoculation, the cells grew adherent to the wall, the supernatant was discarded and H was added to a final concentration of 200. mu. mol/L₂O₂The medium was cultured for 4 hours, and then replaced with the composition culture solution having the final concentrations of 50. mu.g/mL and 10. mu.g/mL, respectively, to continue the culture for 24 hours. Setting no H at the same time of experiment₂O₂Blank control and addition of H alone₂O₂The cell survival status was determined by MTT method: mu.L of MTT stock was added to each well at a final concentration of 2 mg/mL. After continuing culturing for 4 hours, discarding the supernatant, adding 100 μ L of DMSO into each well, measuring the absorbance A of each well at 490nm with an automatic microplate reader after 10min, and calculating the survival rate of the cells. The experimental data are expressed as means ± standard deviation, and the experimental results are shown in table 2.

TABLE 2 survival rates of human umbilical vein endothelial cells and PC-12 cells

The above results indicate that the control groups 1 to 6 can increase H compared with the model control group₂O₂The nucleotide-containing compositions of examples 1-3 significantly increased H survival after treatment₂O₂The survival rate of the treated cells was almost indistinguishable from the blank control test results, further demonstrating that the nucleotide-containing compositions of examples 1-3 have very superior repair characteristicsThe cellular effect.

2. Evaluation test of intracellular ROS level

Hydrogen peroxide acts on cells to generate a large amount of ROS, which attacks cell membranes, proteins and nucleic acids, resulting in cell damage. Digesting the cells in logarithmic growth phase into single cell suspension, and regulating cell concentration to 10⁵one/mL, seeded in 96-well cell culture plates at 100 μ L per well, 6 parallel wells per group. 24 hours after inoculation, the cells grew adherent to the wall, the supernatant was discarded and H was added to a final concentration of 200. mu. mol/L₂O₂The culture medium of (4) was cultured for 4 hours, and then replaced with culture solutions of the compositions each having a final concentration of 50. mu.g/mL, and the culture was continued for 24 hours. Setting no H at the same time of experiment₂O₂Blank control and addition of H alone₂O₂The evaluation of intracellular reactive oxygen species using the reactive oxygen species detection kit of (1): add 10. mu. mol/L of DCFH-DA stock solution (DMSO in solution) to each well to a final concentration of 1. mu. mol/L. After continuously culturing for 2 hours, discarding the supernatant, adding 100 mu L of PBS into each hole, washing for 2 times, suspending the cells by using 200 mu L of PBS after centrifugation, measuring the fluorescence intensity of each hole under the conditions of 485nm excitation wavelength and 525nm emission wavelength by using a fluorescence microplate reader, and calculating the active oxygen content of the cells. The experimental data are expressed as means ± standard deviation, and the experimental results are shown in table 3.

TABLE 3 reactive oxygen species content in human umbilical vein endothelial cells and PC-12 cells

The above results indicate that the nucleotide-containing compositions of examples 1 to 3 can significantly reduce reactive oxygen species in model cells, and that the nucleotide-containing compositions of examples 1 to 3 have excellent protective and repairing effects on oxidatively damaged cells, as compared with the compositions of model controls and control groups 1 to 6.

Experimental example 8

In order to better verify the effect of the nucleotide-containing composition of the present invention on delaying aging, a mouse with a tendency to rapid aging (SAMP 8, available from Experimental animals technologies, Inc., Wei Tony, Beijing) was used as a model animal, and the nucleotide-containing composition of the present invention was used as an intervening material to conduct a long-term feeding study to investigate the effects of the nucleotide-containing compositions of examples 1 to 3 on improving the mouse's ability to autonomously move, learning and memory, brain injury and olfactory sensation, and improving muscle attenuation. Taking 110 mice with rapid aging tendency, the body weight of which is (20 +/-5) g, randomly dividing the mice into 11 groups, taking a basic feed as a positive control group, taking SAMP 8 with the age of 3 months as a negative control group, taking a compound nucleotide which is only fed with the same amount and the same proportion of the tablets in the example 1 as a control experiment 1, taking a compound nucleotide which is only fed with the same amount and the same proportion of the tablets in the example 3 as a control experiment 2, taking a composition which is only fed with the same amount and the same proportion of tea polyphenol, resveratrol, coenzyme Q10 and nicotinamide as the tablets in the example 1 as a control experiment 3, taking a composition which is only fed with the same amount and the same proportion of astragalus polysaccharide, curcumin, resveratrol and nicotinamide as the tablets in the example 2 as a control experiment 4, taking a marine fish oligopeptide which is only fed with the same amount and the same proportion of the tablets in the example 3 as a control experiment 5, and the effect of the nucleotide-containing composition on delaying senescence is verified by taking the same dosage of beta-Nicotinamide Mononucleotide (NMN) as a control experiment 6 and combining various behavioral morphology detection methods.

1. Improvement of mouse's ability to move autonomously with nucleotide-containing composition- -open field experiment

The study performed open field experiments at 9 months of age of the experimental animals, i.e. 6 months after the intervention of the nucleotide-containing composition (1 tablet each, 1 time per day). The open field behavior analysis mainly reflects the autonomous activity ability of animals and the exploration, habit and accompanying emotional changes of new environments, and is an experiment for evaluating the spontaneous activity ability of mice. The principle of the method is that the mice are afraid of the nature of a spacious and bright field, and meanwhile, the mice can generate curiosity to explore in the face of fresh things, and when the mice are anxious, the exploration of a central area can be reduced, and the mice tend to stay in a marginal area; the number of crossing grids and the number of standing grids are reflected by the exploration behaviors and the excitability of the animals, the central grid time reflects the cognitive ability of the animals to the environment, and normal animals can leave the central grid quickly and move around the periphery by avoiding the open environment. The experimental data are expressed as means ± standard deviation, and the experimental results are shown in table 4.

TABLE 4 influence of nucleotide-containing compositions on the ability of mice to voluntarily move

As can be seen from the above, the nucleotide-containing compositions of examples 1 to 3 significantly improved the spontaneous motility and exploratory ability of the mice prone to rapid aging, as compared with the control groups 1 to 6.

2. Improvement of non-spatial medical memory ability of mouse by nucleotide-containing composition-novel object identification experiment

The study performed a new object identification experiment at 9 months of age of the experimental animals, i.e. 6 months after the intervention of the nucleotide-containing composition (1 tablet per time, 1 time per day). The experiment for identifying new object is a learning and memory test method established by utilizing the principle that animals have exploration tendency to new objects in nature, is used for detecting the non-space learning and memory ability of mice, and is a test for memory retention ability established on the basis of the spontaneous exploration behavior of the mice to the new and different objects. The method has the characteristic that the mouse can carry out learning and memory tests in a free activity state, and can more approximately simulate the learning and memory behaviors of human beings. At the same time, the experiment also allows to test the development of long-term or short-term memory mechanisms and the evaluation of the impact of memory development at specific stages in animals, by flexible transformation of new objects (shape, size, etc.). The experiment can reflect the spontaneous memory ability of the mouse, and is a novel important ethological method for evaluating the brain function at present.

TABLE 5 influence of nucleotide-containing compositions on the time(s) of exploring mouse new and old objects

Group of	Old object	New object	Identification index
				Positive control group	16.2±3.0	23.0±10.7	46.9
Negative control group	15.2±10.8	35.5±10.5	70.0
				Control experiment 1	16.8±9.2	29.3±9.6	63.5
Control experiment 2	20.5±6.8	30.0±8.2	59.4
				Control experiment 3	18.1±7.0	29.8±10.5	62.5
Control experiment 4	20.6±7.5	32.3±11.9	61.0
				Control experiment 5	19.9±5.4	32.0±9.0	61.6
Control experiment 6	17.4±8.2	23.6±9.4	57.6
				Example 1	13.7±9.5	34.7±12.9	71.7
Example 2	16.1±4.7	37.9±5.4	70.2
				Example 3	18.1±9.9	35.8±12.6	66.4

From the above experimental results, it can be seen that the mice of examples 1-3 all searched for new objects significantly longer than the old objects compared to the control groups 1-6, indicating that the nucleotide-containing composition of examples 1-3 significantly improves the spontaneous memory of the mice prone to rapid aging.

3. Improvement of nucleotide-containing composition on brain injury of mice-nesting experiment

The nesting experiments were performed in this study at 9 months of age of the experimental animals, i.e. 6 months after the intervention of the nucleotide-containing composition (1 tablet per time, 1 time per day). The nesting behavior is an instinctive behavior of the mouse, the operation is simple, no damage is caused, and the brain damage condition of the mouse can be reflected. Studies have shown that the ability of mice to nest is regulated by neurotransmitters and controlled by numerous brain regions. The mouse with normal and intact brain function has excellent nesting ability. The old padding is discarded one day before the experiment, quantitative wood shavings are put into the padding, and 16 soft paper sheets (4.5cm multiplied by 4.5cm) are evenly put into each cage to be used as nest materials of the mice. The nesting effect of each group of mice was scored in four-point blind method at 12h, 18h and 24h after the start of the experiment, the result of the experiment was scored as the score of the nesting behavior of the mice at the time point by the average scoring value of three experimenters, and the result of the experiment is shown in table 7.

TABLE 6 nesting scores of groups of mice at 12h, 18h, and 24h

Group of	12h	18h	24h
				Positive control group	1.6±0.7	2.5±0.9	2.6±0.6
Negative control group	2.7±0.8	4.9±1.0	6.3±0.5
				Control experiment 1	2.4±0.5	3.2±0.7	3.8±0.7
Control experiment 2	1.9±0.7	2.7±0.9	3.3±0.8
				Control experiment 3	2.2±0.6	3.2±0.4	3.9±0.4
Control experiment 4	2.1±0.4	3.3±0.5	3.7±0.5
				Control experiment 5	1.8±0.9	2.9±1.0	3.5±0.7
Control experiment 6	1.7±1.0	2.7±0.8	3.1±0.5
				Example 1	2.3±0.4	4.2±0.4	5.3±0.5
Example 2	2.5±0.8	4.5±1.1	4.9±1.1
				Example 3	2.0±0.5	4.0±0.6	4.6±0.7

According to the experimental results, the nesting quality of each group of mice is not obviously different at 12h (initial nesting); along with the extension of the nesting time of the mice and the increase of the sign of biting the soft paper by each group of mice, the nesting quality is also improved, when the nesting is carried out for 24h, the nesting quality scores of the mice in the groups of examples 1 to 3 are higher, and the results are almost not obviously different from the test results of a negative control group, which shows that the nucleotide-containing composition in the examples 1 to 3 can effectively improve the nesting capacity of the aged mice and improve the brain damage degree of the mice.

4. Olfactory memory test for improving olfactory memory of mice by using nucleotide-containing composition

Olfactory memory tests were performed in this study at 9 months of age of the test animals, i.e., 6 months after the intervention of the nucleotide-containing composition (1 tablet per time, 1 time per day). The learning and memory ability, food searching ability and the like of the olfactory sensitive animals have high correlation with the olfactory sense, and the change of the olfactory function of the olfactory sensitive animals can be judged by observing and recording the change of the ethology of the olfactory sensitive animals. The principle of olfactory memory test is that the animal smell adapts with the increase of the exposure times of a certain object with special smell, and according to the characteristic, the memory capacity of the animal to the smell is reflected, and the test is divided into an adaptation period (the first day) and a detection period (the second day). Two odors selected in the experiment: mint essence, lemon essence odors, which the mouse had no preference for, each odor allowed the mouse to explore freely for 30s, repeated four times each time, and then the time each time the mouse sniffed the centrifuge tube was recorded. The sniff time is defined as: the experimental results are shown in table 7, excluding the time it takes for the mouse to bite or climb the centrifuge tube when the mouse is facing the centrifuge tube and the nose is within 1cm of the centrifuge tube circumference.

TABLE 7 Effect of nucleotide-containing compositions on the sniffing time(s) of mice

As is clear from the results in Table 7, the mice of examples 1 to 3 were able to adapt to the above-mentioned gas in a shorter time than the positive control experiment group and the control experiments 1 to 6, and thus it was found that the nucleotide-containing compositions of examples 1 to 3 were able to improve the odor adaptation behavior of the mice and have a protective effect on the olfactory memory of the aged mice.

It will be apparent to those skilled in the art from this disclosure that many changes and modifications can be made, or equivalents modified, in the embodiments of the invention without departing from the scope of the invention. Therefore, any simple modification, equivalent change and modification made to the above embodiments according to the technical essence of the present invention shall still fall within the protection scope of the technical solution of the present invention, unless the contents of the technical solution of the present invention are departed.