Regenerative active anti-aging factor micromolecular anti-saccharification composition and application thereof

Abstract

The invention relates to the technical field of functional food, and particularly discloses a regenerative active anti-aging factor micromolecular anti-saccharification composition and application thereof.The composition is prepared from, by weight, 300-460 parts of antioxidant and 120-160 parts of natural anti-saccharification matter, and the antioxidant comprises ergothioneine and high-activity superoxide dismutase. A perfect anti-aging network is formed through multi-layer coverage of an anti-oxidation network, multi-channel blocking of anti-saccharification and joint optimization of mitochondrial functions and cell metabolism, the activity of superoxide dismutase in the gastrointestinal environment is improved through the carrier, the utilization rate of superoxide dismutase is increased, and on this basis, the anti-aging effect of superoxide dismutase is improved. Magnesium threonate is additionally added to regulate energy metabolism in cells and permeability of cell membranes, and a better physiological environment is provided for metabolism and utilization of active substances.

Description

Technical Field

[0001] The present invention belongs to the technical field of functional foods, and particularly relates to a small molecule anti-glycation composition of regenerative active anti-aging factors and its application. Background Art

[0002] Anti-aging research has always been an important focus in the field of life sciences. Research from the mid-20th century to the early 21st century has shown that during the process of cell aging, cell aging-related secretory phenotype factors (SASP) are secreted, and these factors can cause the loss of the extracellular matrix (such as collagen, elastin, hyaluronic acid), accelerating tissue aging. In addition, the aging mechanism is also accompanied by the expression of the mTOR pathway and an increase in reactive oxygen species (ROS) generated by mitochondrial respiratory complexes.

[0003] In recent years, with the in-depth study of the role of advanced glycation end products (AGEs) in the aging process, anti-glycation has gradually become an important direction in the anti-aging field. It has been found that the accumulation of AGEs is closely related to various aging-related diseases such as skin aging and cardiovascular diseases. Driven by market demand, related products have emerged continuously. For example, patent CN113024662B provides an easily digestible anti-glycation collagen peptide, which can be used as a raw material for drugs, health foods, and foods, and can be used to improve skin moisture and vascular elasticity. Another example is patent CN116235948B, which through the synergistic effect among mangosteen extract containing polyphenols, green tea extract containing tea polyphenols, and extract of Cytisus scoparius containing polyphenols, makes the composition have good anti-glycation efficacy and also has antioxidant efficacy. However, the above-mentioned oral anti-aging and anti-glycation products have defects such as low bioavailability and instability in the cellular environment, resulting in limited anti-aging effects. Therefore, there is an urgent need in the market for an anti-aging and anti-glycation product with stable active ingredients and high utilization rate. Summary of the Invention

[0004] In order to overcome the deficiencies of the above-mentioned prior art, the present invention provides a small molecule anti-glycation composition of regenerative active anti-aging factors. The active components include ergothioneine, superoxide dismutase, R-lipoic acid, and Pomella pomegranate extract. This composition forms a relatively complete anti-aging network through multi-level coverage of the antioxidant network, multi-pathway blockade of anti-glycation, and combined optimization of mitochondrial function and cell metabolism. Moreover, through the carrier, the activity of superoxide dismutase in the gastrointestinal environment is improved, and the utilization rate of active substances is increased. On this basis, magnesium threonate is additionally added to regulate the energy metabolism inside the cell and the permeability of the cell membrane, providing a better physiological environment for the metabolism and utilization of active substances.

[0005] To achieve the above object, the technical solution adopted by the present invention is:

[0006] On the one hand, the present invention provides a small molecule anti-glycation composition of regenerated active anti-aging factors, which comprises the following components by weight: 300-460 parts of antioxidants and 120-160 parts of natural anti-glycation agents, wherein the antioxidants include ergothioneine and highly active superoxide dismutase.

[0007] Through the synergy of antioxidants and natural anti-glycation agents, the present invention utilizes their complementary antioxidant and anti-glycation mechanisms to form a relatively perfect anti-aging network.

[0008] In some embodiments, the mass ratio of ergothioneine to highly active superoxide dismutase is 1:(59-76).

[0009] Ergothioneine has good oral absorbability. It enters mitochondria through the transporter OCTN-1, directly scavenges hydroxyl radicals and singlet oxygen, protects mitochondrial DNA, and its antioxidant ability can indirectly reduce the glycation reaction caused by oxidative stress; superoxide dismutase is the core enzyme for scavenging superoxide anions (O2 - ), which can reduce DNA damage caused by lipid peroxidation, thereby delaying aging.

[0010] In some embodiments, the preparation steps of the highly active superoxide dismutase are as follows:

[0011] Prepare a zinc acetate solution and a dimethylimidazole solution. Add superoxide dismutase to the dimethylimidazole solution, then add the zinc acetate solution under ultrasonic conditions. After ultrasonic treatment for 1-5 min, let it stand at room temperature for 8-16 h, centrifuge to collect the solid, wash it, and freeze-dry it to obtain highly active superoxide dismutase.

[0012] In some embodiments, the molar ratio of zinc acetate to dimethylimidazole is 1:(3-5).

[0013] In some embodiments, the mass ratio of superoxide dismutase to dimethylimidazole is (0.03-0.05):1.

[0014] In some embodiments, the activity of superoxide dismutase is 80,000-160,000 enzyme activities.

[0015] Although superoxide dismutase can enter the body through oral absorption and reduce the damage of free radicals to cells, oral administration will also cause partial decomposition of some enzymes in the gastrointestinal tract. The present invention provides a good carrier for superoxide dismutase with zinc metal and dimethylimidazole. This carrier has good biocompatibility and improves the activity of superoxide dismutase in the gastrointestinal environment.

[0016] In addition, the zinc ions contained in the carrier may also enhance the synergistic effect of ergothioneine and R-lipoic acid, more effectively promote the regeneration of glutathione, and improve the antioxidant capacity. Specifically, R-lipoic acid can maintain the antioxidant status of cells by reducing glutathione and other antioxidant molecules, while ergothioneine can activate antioxidant enzymes such as glutathione peroxidase. The two work together to activate the activity of glutathione, and zinc ions can regulate the activities of glutathione reductase and antioxidant enzymes, thereby promoting the regeneration of glutathione.

[0017] In some embodiments, the poly natural anti-glycation agent comprises R-lipoic acid and Pomella pomegranate extract.

[0018] In some embodiments, the mass ratio of R-lipoic acid to Pomella pomegranate extract is 1:(1.0 - 1.3).

[0019] As a natural mitochondrial coenzyme, R-lipoic acid can block the non-enzymatic glycosylation process by chelating metal ions (such as Fe 2+ , Cu 2+ ) and reduce the formation of advanced glycation end products (AGEs); it can also regulate blood glucose metabolism, enhance insulin sensitivity, and reduce glycation reactions caused by hyperglycemia; in addition, R-lipoic acid can also reduce oxidative stress-induced cell damage and delay aging by neutralizing free radicals and regenerating endogenous antioxidants (such as glutathione). Pomella pomegranate extract is rich in ellagitannins, which can be metabolically converted by gut microbiota into urolithin A (Uro-A). This substance can induce mitophagy and clear aged and damaged mitochondria, thereby delaying aging; in addition, Pomella pomegranate extract can directly block the generation of AGEs by scavenging reactive carbonyl compounds (such as methylglyoxal), achieving a high inhibition rate.

[0020] In some embodiments, the composition further comprises 20 - 40 parts by weight of magnesium threonate.

[0021] The present invention utilizes R-lipoic acid, which reduces the formation of AGEs, and superoxide dismutase, which reduces free radical damage to cells, to form the first anti-aging defense line; and further repairs damage at the cellular and mitochondrial levels through Pomella pomegranate extract and ergothioneine. On this basis, the present invention delays systemic aging from the perspectives of metabolism and neuroprotection through magnesium threonate. The special structure of magnesium threonate enhances the penetration of the blood-brain barrier, increases the magnesium concentration in the brain, activates BDNF (brain-derived neurotrophic factor), delays cognitive aging, reduces oxidative stress damage to neurons, and the magnesium ions contained in magnesium threonate can improve the insulin signaling pathway, reduce insulin resistance, and indirectly reduce glycation reactions; further, in the present invention, magnesium threonate can regulate intracellular energy metabolism and the permeability of cell membranes, which provides a better physiological environment for the metabolism and utilization of antioxidants and natural antiglycation agents.

[0022] On the other hand, the present invention provides the application of the above composition in capsules, tablets, and liquid preparations.

[0023] Compared with the prior art, the present invention has the following beneficial effects:

[0024] 1. The regenerative active anti-aging factor small molecule antiglycation composition provided by the present invention achieves multi-level coverage of the antioxidant network through free radical scavenging division of labor, forming a three-dimensional defense system. Among them, superoxide dismutase scavenges superoxide anions (O2 - ), R-lipoic acid and ergothioneine target hydroxyl radicals (·OH) and lipid peroxides, and Pomella pomegranate extract neutralizes reactive carbonyl compounds.

[0025] 2. The present invention uses source inhibition and terminal intervention to achieve multi-pathway blockade of antiglycation. Among them, magnesium threonate regulates blood sugar metabolism and reduces glycation substrates; R-lipoic acid and superoxide dismutase reduce oxidative stress and block the initiation of glycation reactions; further, pomegranate extract and ergothioneine directly inhibit the formation of AGEs and protect collagen and elastin.

[0026] 3. The R-lipoic acid and ergothioneine adopted by the present invention enhance mitophagy through the AMPK / SIRT1 pathway, Uro-A derived from Pomella pomegranate extract promotes the clearance of senescent mitochondria, and magnesium threonate improves energy metabolism efficiency. The combination of the three realizes the combined optimization of mitochondrial function and cell metabolism.

[0027] 4. The present invention provides a good carrier for superoxide dismutase through metal zinc and dimethylimidazole, improves its activity in the gastrointestinal environment, and the zinc ions contained in the carrier can regulate the activities of glutathione reductase and antioxidant enzymes, thereby enhancing the synergistic effect of ergothioneine and R-lipoic acid, more effectively promoting the regeneration of glutathione, and improving the antioxidant capacity. Detailed implementation manners

[0028] The present invention will be described below in conjunction with specific implementation manners. It should be noted that the following examples are examples of the present invention, only for explaining the present invention, and not for limiting the present invention. Without departing from the gist or scope of the present invention, other combinations and various improvements within the concept of the present invention can be made.

[0029] It is worth noting that the raw materials used in the following preparation examples and examples, if not specifically stated, are from any commercially available manufacturer.

[0030] Preparation Example 1

[0031] The preparation steps of highly active superoxide dismutase A are as follows:

[0032] Prepare a 20 mmol / L zinc acetate solution and a 120 mmol / L dimethylimidazole solution. Add 1.5 mg of superoxide dismutase with an activity of 100,000 to 4 mL of the dimethylimidazole solution, and then add 6 mL of the zinc acetate solution under ultrasonic conditions. After ultrasonic treatment for 2 min, let it stand at room temperature for 12 h, centrifuge to collect the solid, wash with deionized water, and freeze-dry to obtain highly active superoxide dismutase A.

[0033] Preparation Example 2

[0034] The difference in the preparation steps of highly active superoxide dismutase B from Preparation Example 1 is that the amount of the zinc acetate solution used is 9 mL.

[0035] Preparation Example 3

[0036] The difference in the preparation steps of highly active superoxide dismutase C from Preparation Example 1 is that the amount of the zinc acetate solution used is 4.5 mL.

[0037] Preparation Example 4

[0038] The difference in the preparation steps of highly active superoxide dismutase D from Preparation Example 1 is that the amount of superoxide dismutase used is 0.8 mg.

[0039] Preparation Example 5

[0040] The difference in the preparation steps of highly active superoxide dismutase E from Preparation Example 1 is that the amount of superoxide dismutase used is 2.2 mg.

[0041] Example 1

[0042] A small molecule anti-glycation composition of regenerative active anti-aging factors, calculated by weight, comprises the following components: 405 parts of antioxidants, 148 parts of natural anti-glycation agents, and 30 parts of magnesium threonate. The antioxidants include 5 parts of ergothioneine and 400 parts of highly active superoxide dismutase A. The natural anti-glycation agents include 68 parts of R-lipoic acid and 80 parts of Pomella pomegranate extract.

[0043] Example 2

[0044] A small molecule anti-glycation composition of regenerative active anti-aging factors, calculated by weight, comprises the following components: 300 parts of antioxidants, 120 parts of natural anti-glycation agents, and 20 parts of magnesium threonate. The antioxidants include 5 parts of ergothioneine and 295 parts of highly active superoxide dismutase A. The natural anti-glycation agents include 60 parts of R-lipoic acid and 60 parts of Pomella pomegranate extract.

[0045] Example 3

[0046] A small molecule anti-glycation composition of regenerative active anti-aging factors, calculated by weight, comprises the following components: 460 parts of antioxidants, 160 parts of natural anti-glycation agents, and 40 parts of magnesium threonate. The antioxidants include 6 parts of ergothioneine and 454 parts of highly active superoxide dismutase A. The natural anti-glycation agents include 70 parts of R-lipoic acid and 90 parts of Pomella pomegranate extract.

[0047] Example 4

[0048] A small molecule anti-glycation composition of regenerative active anti-aging factors, calculated by weight, comprises the following components: 405 parts of antioxidants, 148 parts of natural anti-glycation agents. The antioxidants include 5 parts of ergothioneine and 400 parts of highly active superoxide dismutase A. The natural anti-glycation agents include 68 parts of R-lipoic acid and 80 parts of Pomella pomegranate extract.

[0049] Example 5

[0050] This example provides a small molecule anti-glycation composition of regenerative active anti-aging factors. The specific implementation method is the same as that of Example 1, except that: highly active superoxide dismutase A is replaced by an equal amount of highly active superoxide dismutase B.

[0051] Example 6

[0052] This example provides a small molecule anti-glycation composition of regenerative active anti-aging factors. The specific implementation method is the same as that of Example 1, except that: highly active superoxide dismutase A is replaced by an equal amount of highly active superoxide dismutase C.

[0053] Example 7

[0054] This embodiment provides a small molecule anti-glycation composition with regenerative active anti-aging factors. The specific implementation is the same as that of Example 1, except that highly active superoxide dismutase A is replaced by an equal amount of highly active superoxide dismutase D.

[0055] Example 8

[0056] This embodiment provides a small molecule anti-glycation composition with regenerative active anti-aging factors. The specific implementation is the same as that of Example 1, except that highly active superoxide dismutase A is replaced by an equal amount of highly active superoxide dismutase E.

[0057] Comparative Example 1

[0058] This comparative example provides a small molecule anti-glycation composition with regenerative active anti-aging factors. The specific implementation is the same as that of Example 1, except that highly active superoxide dismutase A is replaced by superoxide dismutase with the same activity.

[0059] Performance test:

[0060] 1. Enzyme stability test: This test was carried out according to the determination of in vitro simulated digestion stability in 2.2.2.6 of the master's and doctoral thesis "Research on the Improvement of Ulcerative Colitis by SOD Self-Assembled Nanoparticles - Li Qiaoling" to obtain the enzyme activity recovery rate (%). The higher the enzyme activity recovery rate, the stronger the enzyme stability.

[0061] 2. Anti-glycation ability test: Using the BSA-fructose simulation reaction system, 1 mL of fructose solution (1.5 mol / L) was mixed with 20 mg of the composition provided in Examples 1-8 and Comparative Example 1. After incubation at 37 °C for 2 h, 1 mL of 30 mg / mL BSA solution was added. The above solutions were all dissolved in 50 mmol / L pH 7.4 phosphate buffer (containing 0.1% sodium azide). Using 20 mL of the above phosphate buffer instead of the composition as the blank group, after incubating each sample in a biochemical incubator at 37 °C for 6 d, the fluorescence intensity of each sample was measured under the conditions of excitation wavelength 370 nm and emission wavelength 440 nm. The formula for the inhibition rate R of the formation of fluorescent AGEs is as follows: R = (1 - FA / FB) × 100%, where: FA is the fluorescence intensity of each sample group; FB represents the fluorescence intensity of the blank group.

[0062] 3. Antioxidant performance test: This test was carried out according to the journal "Purification and Antioxidant, Whitening, Moisturizing and Humidifying Activities of Acid Sheared Fragments of Angelica Polysaccharide" for ·OH scavenging rate and O2 - scavenging rate test,

[0063] The results are shown in Table 1.

[0064] Table 1

[0065] Enzyme Activity Recovery Rate (%) Inhibition Rate R (%) ·OH Scavenging Rate (%) <![CDATA[O2 - Clearance rate (%)]]> Example 1 80.24 21.64 24.23 22.16 Example 2 78.41 19.16 21.37 19.78 Example 3 78.93 21.08 22.65 20.59 Example 4 77.49 16.19 21.03 18.96 Example 5 71.25 18.53 20.32 16.22 Example 6 68.99 17.84 20.05 15.79 Example 7 76.68 17.27 19.37 16.37 Example 8 77.11 18.20 19.21 18.13 Comparative Example 1 54.62 15.75 15.36 15.24

[0066] As can be seen from the data in Table 1, Examples 1 to 3 exhibit good enzyme stability, anti-glycation ability and antioxidant ability. Compared with Example 1, magnesium threonate is missing in Example 4, resulting in a decrease in the inhibition rate of AGEs. The possible reason is that magnesium threonate can reduce glycation substrates and is also beneficial to the metabolism and utilization of related active substances.

[0067] Compared with Example 1, in Examples 5 to 6 and 7 to 8, the amounts of zinc acetate and superoxide dismutase were changed respectively during the synthesis of highly active superoxide dismutase. The former has a certain impact on the synthesis of the carrier, resulting in changes in enzyme stability. In terms of the overall anti-glycation ability, other active substances can effectively make up for it, but superoxide dismutase has a greater impact on the scavenging of O2 - ; for the latter, the amount of superoxide dismutase affects the effective content in the carrier, has little impact on stability, but will affect the anti-glycation ability and the scavenging ability of O2 - .

[0068] Compared with Example 1, in Comparative Example 1, superoxide dismutase was directly used without the presence of a carrier, which is not conducive to the stability of the enzyme in the gastrointestinal environment. And from the decrease in the scavenging rate of ·OH, it can be seen that the carrier is also beneficial to the improvement of antioxidant ability.

[0069] The above-mentioned examples and comparative examples do not impose any formal restrictions on the present invention. Although the present invention has been disclosed above with preferred embodiments, it is not intended to limit the present invention. Any person skilled in the art, without departing from the scope of the technical solution of the present invention, may make some changes or modifications to the above-disclosed technical content to obtain equivalent embodiments with equivalent changes. However, any simple modification, equivalent change and modification made to the above embodiments based on the technical essence of the present invention without departing from the content of the technical solution of the present invention still fall within the scope of the technical solution of the present invention.

Claims

1. A small molecule anti-glycation composition of regenerative active anti-aging factors, characterized in that: The invention comprises the following components by weight: 300-460 parts of antioxidants and 120-160 parts of natural anti-glycation substances, wherein the antioxidants comprise ergothioneine and highly active superoxide dismutase.

2. The regenerative active anti-aging factor small molecule anti-glycation composition according to claim 1, characterized in that: The mass ratio of ergothioneine to high-activity superoxide dismutase is 1:(59-76).

3. The regenerative active anti-aging factor small molecule anti-glycation composition according to claim 1, characterized in that: The preparation steps of the highly active superoxide dismutase are as follows: A zinc acetate solution and a dimethylimidazole solution are prepared, superoxide dismutase is added to the dimethylimidazole solution, and then the zinc acetate solution is added under ultrasonic conditions. After ultrasonication for 1 to 5 minutes, the mixture is allowed to stand at room temperature for 8 to 16 hours, and solids are collected by centrifugation, washed, and freeze-dried to obtain highly active superoxide dismutase.

4. The regenerative active anti-aging factor small molecule anti-glycation composition according to claim 3, characterized in that: The molar ratio of zinc acetate to dimethylimidazole is 1:(3-5).

5. The regenerative active anti-aging factor small molecule anti-glycation composition according to claim 3, characterized in that: The mass ratio of the superoxide dismutase to dimethylimidazole is (0.03-0.05):

1.

6. The regenerative active anti-aging factor small molecule anti-glycation composition according to claim 3, characterized in that: The activity of the superoxide dismutase is 80,000 to 160,000 enzyme activities.

7. The regenerative active anti-aging factor small molecule anti-glycation composition according to claim 1, characterized in that: The polynatural anti-glycation compound comprises R-lipoic acid and Pomella pomegranate extract.

8. The regenerative active anti-aging factor small molecule anti-glycation composition according to claim 6, characterized in that: The mass ratio of the R-lipoic acid to the Pomella red pomegranate extract is 1:(1.0-1.3).

9. The regenerative active anti-aging factor small molecule anti-glycation composition according to claim 1, characterized in that: The components further comprise 20 to 40 parts by weight of magnesium threonate.

10. Use of the small molecule anti-glycation composition of regenerative active anti-aging factors according to any one of claims 1 to 8 in capsules, tablets and liquid preparations.