An Anti-aging composition with AKG-PQQ synergistically enhancing mitochondrial function

Abstract

The present invention discloses an anti-aging composition synergistically enhancing mitochondrial function with AKG and PQQ, belonging to the technical field of anti-aging. The composition comprises AKG, PQQ disodium salt, Agaricus bisporus extract, and a single excipient. AKG, in anhydrous crystal form as 2-oxoglutaric acid, directly participates in mitochondrial energy metabolism and provides core substrate support. PQQ disodium salt promotes mitochondrial biogenesis, ensuring structural renewal and maintaining mitochondrial activity. The β-glucan and ergothioneine naturally contained in the Agaricus bisporus extract further support the normal physiological state of mitochondria through synergistic effects. The single excipient is only physically mixed with the active ingredients, reducing interference caused by excipient interactions and ensuring that the efficacy of each active component is fully exerted.

Description

[0001] DESCRIPTION

[0002] An anti-aging composition with AKG-PQQ synergistically enhancing mitochondrial function

[0003] TECHNICAL FIELD

[0004] The present invention relates to the technical field of anti-aging functions, and specifically to an anti-aging composition with AKG-PQQ synergistically enhancing mitochondrial function.

[0005] BACKGROUND

[0006] Aging is a natural decline process of physiological functions occurring in an organism over time. Mitochondrial dysfunction is a significant cause inducing aging. As the core of cellular energy metabolism, the functional state of mitochondria directly affects the normal physiological activities of cells, thereby correlating with the overall aging process of the organism. With the increasing health demands, regulating mitochondrial function and delaying aging through functional compositions has become a current research hotspot. Anti-aging compositions compounded with natural active ingredients have gained widespread attention due to their safety advantages.

[0007] However, most anti-aging products currently on the market have a single mechanism of action and struggle to intervene in the aging process synergistically from multiple dimensions such as energy metabolism, mitochondrial biogenesis, and antioxidant activity. They do not incorporate substances like Agaricus bisporus extract, which contains natural active ingredients, and thus cannot form a multi-dimensional system for regulating mitochondrial function. Furthermore, the excipients selected for anti-aging compositions are often in the form of multiple complex mixtures, which can easily lead to interactions between excipients, potentially interfering with the effects of the active ingredients. Concurrently, the preparation of the composition lacks standardized control; the operations for extract preparation and granulation are crude, easily causing loss of active ingredients and making it difficult to ensure the stable effect of the composition.

[0008] SUMMARY

[0009] An objective of the present invention is to address the deficiencies of the prior art and provide an anti-aging composition with AKG-PQQ synergistically enhancing mitochondrial function. The present invention achieves this by combining AKG, PQQ disodium salt, Agaricus bisporus extract with a single excipient. AKG, as 2-oxoglutaric acid in an anhydrous crystal form, directly participates in the energy metabolism process of mitochondria, providing core substrate support for mitochondrial function. PQQ disodium salt plays a role in promoting mitochondrial biogenesis, ensuring the structural renewal and physiological activity of mitochondria. The P-glucan and ergothioneine naturally contained in the Agaricus bisporus extract form a synergistic effect, maintaining the normal physiological state of mitochondria from multiple dimensions. The single excipient only undergoes physical mixing with the active ingredients, avoiding interference with the function of the active ingredients caused by interactions between multiple excipients, thereby ensuring that the effects of each active ingredient are fully exerted.

[0010] To solve the above technical problems, the present invention provides the following technical solutions: In one aspect, an anti-aging composition with AKG-PQQ synergistically enhancing mitochondrial function is provided, characterized in that the composition comprises, in parts by weight:

[0011] AKG: 40-65 parts;

[0012] PQQ disodium salt: 0.05-0.5 parts;

[0013] Agaricus bisporus extract: 15-35 parts;

[0014] Excipient: 10-20 parts.

[0015] Further, the AKG is 2-oxoglutaric acid, in an anhydrous crystal form, having a water solubility of not less than 100 g / L, is not chemically modified, and is used directly as an active ingredient. Furthermore, the PQQ disodium salt is pyrroloquinoline quinone disodium salt, in the form of a white to pale yellow crystalline powder, readily soluble in water, having a residual solvent content of <0.001%.

[0016] Furthermore, the Agaricus bisporus extract is an extract obtained from Agaricus bisporus through a water extraction and alcohol precipitation process, the extraction raw material being fresh or dried Agaricus bisporus fruiting bodies, naturally containing P-glucan and ergothioneine; wherein the Agaricus bisporus extract has a mass percentage content of P-glucan of 10-30%, a mass percentage content of ergothioneine of 0.001-0.01%, a loss on drying of <5%, the extract being a light yellow to brownish powder, having a water-soluble extractive content of >40%.

[0017] Furthermore, the excipient is one selected from the group consisting of mannitol, lactose, microcrystalline cellulose, and magnesium stearate, and the excipient is a food-grade raw material, with no industrial-grade raw material added, and the excipient only undergoes physical mixing with AKG, PQQ disodium salt, and Agaricus bisporus extract, with no chemical cross-linking reaction occurring.

[0018] In another aspect, a preparation method for an anti-aging composition with AKG-PQQ synergistically enhancing mitochondrial function is provided, the method comprising:

[0019] Raw material pretreatment: performing a water extraction and alcohol precipitation pretreatment process on Agaricus bisporus fruiting bodies to obtain the Agaricus bisporus extract, then respectively subjecting AKG, PQQ disodium salt, the Agaricus bisporus extract, and the excipient to pretreatment including impurity removal and grinding;

[0020] Ingredient mixing: putting the pretreated AKG, PQQ disodium salt, Agaricus bisporus extract, and excipient into mixing equipment according to a predetermined proportion, and mixing with stirring to obtain a uniform mixed material; Material shaping: performing a shaping operation on the mixed material using a dry granulation process to obtain a preliminarily shaped material;

[0021] Drying treatment: placing the preliminarily shaped material in a drying equipment for a drying operation to remove free moisture; processing the dried material to remove agglomerated material, obtaining the finished composition.

[0022] Furthermore, in the raw material pretreatment, the water extraction and alcohol precipitation pretreatment process for Agaricus bisporus fruiting bodies comprises: crushing the Agaricus bisporus fruiting bodies, adding water for extraction, then adding ethanol to adjust the alcohol concentration of the system, allowing to stand, centrifuging to obtain a precipitate, and drying the precipitate; wherein the solid-liquid ratio for water extraction is 1:8-15, the extraction temperature is 70-90°C, and the extraction time is 1-3 h; the alcohol concentration for alcohol precipitation is 60-80%, the standing temperature is 4- 10 °C, the standing time is 8-16 h, the centrifugation speed is 3000-5000 r / min, and the centrifugation time is 10-20 min; impurity removal is performed using a vibrating screen, with a vibration frequency of the vibrating screen being 20-30 Hz; the grinding time is 5-15 min, the ground material is subjected to sieving treatment with a mesh size of 80-120 mesh, and coarse particles that do not pass through the sieve are removed, retaining only the uniform fine powder material.

[0023] Furthermore, in the ingredient mixing, the proportion of AKG, PQQ disodium salt, Agaricus bisporus extract, and excipient is 40-65:0.05-0.5: 15-35: 10-20; the stirring speed of the mixing equipment is 100-300 r / min, the ambient temperature during the mixing process is 20-25°C, the ambient relative humidity is 40-60%, and stirring is continued until the material is uniformly mixed.

[0024] Furthermore, in the material shaping, the dry granulation process comprises: subjecting the mixed material to pre-sieving using a 16-20 mesh screen, then feeding the pre-sieved material into a dry granulator for tableting, with a roller linear speed of 5-15 m / min and a granulation pressure of 5-15 MPa, to obtain a sheet-like material; then crushing the sheet-like material in the dry granulator, passing the crushed material through a 20-30 mesh screen, subjecting the sieved material to preliminary granulation, and after preliminary granulation, passing it through an 8-30 mesh screen, thereby completing the dry granulation and obtaining preliminarily shaped granular material.

[0025] Furthermore, in the drying treatment, the drying temperature is 40-60°C, the drying time is 2-6 h, and the moisture content after drying is 1-3%.

[0026] Compared with the prior art, the present anti-aging composition with AKG-PQQ synergistically enhancing mitochondrial function possesses the following beneficial effects:

[0027] I. The present invention combines AKG, PQQ disodium salt, Agaricus bisporus extract with a single excipient. AKG, as 2-oxoglutaric acid in an anhydrous crystal form, directly participates in the energy metabolism process of mitochondria, providing core substrate support for mitochondrial function. PQQ disodium salt plays a role in promoting mitochondrial biogenesis, ensuring the structural renewal and physiological activity of mitochondria. The P-glucan and ergothioneine naturally contained in the Agaricus bisporus extract form a synergistic effect, maintaining the normal physiological state of mitochondria from multiple dimensions. The single excipient only undergoes physical mixing with the active ingredients, avoiding interference with the function of the active ingredients caused by interactions between multiple excipients, ensuring that the effects of each active ingredient are fully exerted.

[0028] II. The present invention prepares the extract from Agaricus bisporus fruiting bodies using a water extraction and alcohol precipitation process, completely retaining the natural active ingredients 0-glucan and ergothioneine in the extract. Then, AKG, PQQ disodium salt, the Agaricus bisporus extract, and the single excipient are respectively subjected to pretreatment including impurity removal and grinding, ensuring the fine powder uniformity of each raw material. A physical shaping process of dry granulation is used for material shaping, avoiding damage to active ingredients by chemical modification treatment. Drying treatment removes free moisture from the material, ensuring the stability of the composition. Thus, comprehensive protection for each active ingredient is achieved, ensuring the function of each component in regulating mitochondrial function, allowing the anti-aging effect of the composition to be stably manifested.

[0029] Other advantages, objectives, and features of the present invention will be set forth in part in the following description, and in part will become apparent to those skilled in the art upon examination of the following or may be learned from practice of the invention.

[0030] BRIEF DESCRIPTION OF DRAWINGS

[0031] To explain the technical solutions in the embodiments of the present invention or the prior art more clearly, the following briefly introduces the drawings required for describing the embodiments or the prior art. Obviously, the drawings in the following description are only some embodiments of the present invention. For those of ordinary skill in the art, other drawings can be obtained based on these drawings without inventive effort.

[0032] Figure 1 is a flow chart of the preparation method of an anti-aging composition with AKG-PQQ synergistically enhancing mitochondrial function according to the present invention;

[0033] Figure 2 is a framework diagram of the preparation method of an anti-aging composition with AKG-PQQ synergistically enhancing mitochondrial function according to the present invention;

[0034] Figure 3 is a framework diagram of the raw material pretreatment in the preparation method of an anti-aging composition with AKG-PQQ synergistically enhancing mitochondrial function according to the present invention.

[0035] DETAILED DESCRIPTION

[0036] To further elaborate on the technical means and effects adopted by the present invention to achieve the intended invention objectives, the following, in conjunction with the accompanying drawings and preferred embodiments, provides a detailed description of the specific implementation, structure, features, and effects of the present invention.

[0037] Embodiment 1:

[0038] Raw material preparation (in parts by weight):

[0039] AKG: 50 parts;

[0040] PQQ disodium salt: 0.2 parts;

[0041] Agaricus bisporus extract: 29.8 parts;

[0042] Excipient: 20 parts.

[0043] Raw material specifications:

[0044] AKG: 2-oxoglutaric acid, anhydrous crystal form, water solubility of 110 g / L, not chemically modified, used directly as an active ingredient;

[0045] PQQ disodium salt: pyrroloquinoline quinone disodium salt, white crystalline powder, readily soluble in water, residual solvent content <0.001%;

[0046] Agaricus bisporus extract: prepared from dried Agaricus bisporus fruiting bodies via water extraction and alcohol precipitation process, light yellow powder, wherein the mass percentage content of 0-glucan is 20%, the mass percentage content of ergothioneine is 0.005%, loss on drying is 3%, water-soluble extractive content is 45%;

[0047] Excipient: mannitol, food-grade raw material, no industrial-grade raw material added, only physical mixing with active ingredients, no chemical cross-linking reaction.

[0048] Preparation method:

[0049] Crush dried Agaricus bisporus fruiting bodies, add water for extraction (solid-liquid ratio 1:10, extraction temperature 80 80°C, extraction time 2 h); add ethanol to the extracted filtrate to adjust the alcohol concentration to 70%, stand at 5°C for 12 h, centrifuge at 4000 r / min for 15 min, take the precipitate and dry to obtain Agaricus bisporus extract. Subject AKG, PQQ disodium salt, Agaricus bisporus extract, and mannitol to impurity removal using a vibrating screen (vibration frequency 25 Hz); then grind in a high-speed universal grinder for 10 min, sieve the ground material through a 100-mesh screen, remove coarse particles, retain uniform fine powder material, as shown in Figure 1.

[0050] Put the pretreated AKG, PQQ disodium salt, Agaricus bisporus extract, and mannitol into a three-dimensional motion mixer according to the weight ratio of 50:0.2:29.8:20, stirring speed 200 r / min, mixing environment temperature 23 °C, relative humidity 50%, continue stirring until the material is uniformly mixed, obtaining the mixed material, as shown in Figure 2.

[0051] Subject the mixed material to pre-sieving using an 18-mesh screen, feed the pre-sieved material into a dry granulator for tableting (roller linear speed 10 m / min, granulation pressure 10 MPa), obtain a sheet-like material; crush the sheet-like material in the dry granulator, pass the crushed material through a 25-mesh screen, subject the sieved material to preliminary granulation, after preliminary granulation pass it through a 20-mesh screen, complete the dry granulation, obtaining preliminarily shaped granular material.

[0052] Place the preliminarily shaped granular material in a hot air circulation drying oven for drying (drying temperature 50°C, drying time 4 h), moisture content of the material after drying is 2%; then sieve the dried material, remove agglomerated material, obtain the finished anti-aging composition with AKG-PQQ synergistically enhancing mitochondrial function.

[0053] Physicochemical index detection:

[0054] The finished product is a uniform light yellow granule, with a particle size within the range of 8-30 mesh, no agglomeration, no discoloration; each active ingredient and mannitol are only in a physically mixed state, with no chemical cross-linking reaction occurring; the active ingredient retention rates of AKG, PQQ disodium salt, and Agaricus bisporus extract are 98.6%, 98.9%, and 98.4%, respectively.

[0055] Functional effect detection:

[0056] Select in vitro cultured senescent model hepatocytes, add the anti-aging composition of this embodiment, culture for 48 h, then detect the mitochondrial membrane potential. The results show that the fluorescence intensity of the hepatocyte mitochondrial membrane potential is at a relatively high level, indicating that AKG provides sufficient substrate support for mitochondrial function, PQQ disodium salt assists in mitochondrial structure maintenance, and 0-glucan and ergothioneine in the Agaricus bisporus extract act on the mitochondrial membrane. The three synergistically stabilize the potential difference across the mitochondrial membrane, effectively maintaining the stability of the mitochondrial membrane potential and ensuring mitochondrial electrochemical transmission function.

[0057] Select in vitro cultured senescent model hepatocytes, add the anti-aging composition of this embodiment, culture for 48 h, then detect the mitochondrial ROS level. The results show that the ROS content in mitochondria is significantly reduced, indicating that ergothioneine in the Agaricus bisporus extract exerts an antioxidant effect, and AKG reduces the generation of ROS during mitochondrial metabolism. The two form a synergy with PQQ disodium salt, and together with the physical dispersion characteristic of mannitol, allow each active ingredient to act uniformly on mitochondria, reducing the interference of oxidative damage on mitochondrial function and enhancing the mitochondrial oxidative stress resistance.

[0058] Embodiment 2:

[0059] Raw material preparation (in parts by weight):

[0060] AKG: 60 parts;

[0061] PQQ disodium salt: 0.4 parts;

[0062] Agaricus bisporus extract: 19.6 parts;

[0063] Excipient: 20 parts.

[0064] Raw material specifications:

[0065] AKG: 2-oxoglutaric acid, anhydrous crystal form, water solubility of 105 g / L, not chemically modified, used directly as an active ingredient;

[0066] PQQ disodium salt: pyrroloquinoline quinone disodium salt, pale yellow crystalline powder, readily soluble in water, residual solvent content <0.001%;

[0067] Agaricus bisporus extract: prepared from fresh Agaricus bisporus fruiting bodies via water extraction and alcohol precipitation process, brownish powder, wherein the mass percentage content of P-glucan is 28%, the mass percentage content of ergothioneine is 0.008%, loss on drying is 2.5%, water-soluble extractive content is 48%;

[0068] Excipient: lactose, food-grade raw material, no industrial-grade raw material added, only physical mixing with active ingredients, no chemical cross-linking reaction.

[0069] Preparation method:

[0070] The preparation process of Agaricus bisporus extract, and the impurity removal, grinding, and sieving treatment of AKG, PQQ disodium salt, and lactose are all the same as in Embodiment 1, as shown in Figure 3;

[0071] Put the pretreated raw materials into a three-dimensional motion mixer according to the weight ratio of 60:0.4:19.6:20, stirring speed and mixing environment parameters are consistent with Embodiment 1, stir until the material is uniformly mixed, obtaining the mixed material; io The operation steps and parameters for pre-sieving, tableting, crushing, sieving, and preliminary granulation are all the same as in Embodiment 1, obtaining preliminarily shaped granular material;

[0072] The drying equipment, temperature, time, and sieving operation are all the same as in Embodiment 1, obtaining the finished anti-aging composition with AKG-PQQ synergistically enhancing mitochondrial function.

[0073] Physicochemical index detection:

[0074] The finished product is a uniform brownish granule, with a particle size within the range of 8-30 mesh, no agglomeration, no discoloration; each active ingredient and lactose are only in a physically mixed state, with no chemical cross-linking reaction occurring; the active ingredient retention rates of AKG, PQQ disodium salt, and Agaricus bisporus extract are 98.7%, 99.1%, and 98.5%, respectively.

[0075] Functional effect detection:

[0076] Select in vitro cultured senescent model hepatocytes, add the anti-aging composition of this embodiment, culture for 48 h, then detect the mitochondrial membrane potential. The results show that the fluorescence intensity of the hepatocyte mitochondrial membrane potential is at a relatively high level, indicating that the high content of AKG continuously provides sufficient metabolic substrate for mitochondria, the high proportion of PQQ disodium salt efficiently promotes mitochondrial biogenesis and strengthens the construction and repair of the mitochondrial membrane structure, and the active ingredients in the Agaricus bisporus extract assist in maintaining mitochondrial membrane integrity. The three synergistically and efficiently stabilize the mitochondrial membrane potential, ensuring normal mitochondrial electrochemical transmission and energy conversion functions.

[0077] Select in vitro cultured senescent model hepatocytes, add the anti-aging composition of this embodiment, culture for 48 h, then detect the mitochondrial reactive oxygen species (ROS) level. The results show that the ii ROS content in mitochondria is significantly reduced, indicating that the high content of AKG greatly reduces the generation of reactive oxygen species in mitochondrial metabolism, PQQ disodium salt synergistically alleviates mitochondrial oxidative damage, and ergothioneine and 0-glucan in the Agaricus bisporus extract exert an antioxidant effect. The three, together with the mild dispersion characteristic of lactose, allow the active ingredients to act uniformly on mitochondria, significantly reducing the impact of oxidative damage on mitochondrial function and enhancing the mitochondrial oxidative stress resistance.

[0078] Embodiment 3:

[0079] Raw material preparation (in parts by weight):

[0080] AKG: 45 parts;

[0081] PQQ disodium salt: 0.5 parts;

[0082] Agaricus bisporus extract: 34.5 parts;

[0083] Excipient: 20 parts.

[0084] Raw material specifications:

[0085] AKG: 2-oxoglutaric acid, anhydrous crystal form, water solubility of 108 g / L, not chemically modified, used directly as an active ingredient;

[0086] PQQ disodium salt: pyrroloquinoline quinone disodium salt, pale yellow crystalline powder, readily soluble in water, residual solvent content <0.001%;

[0087] Agaricus bisporus extract: prepared from dried Agaricus bisporus fruiting bodies via water extraction and alcohol precipitation process, brownish-yellow powder, wherein the mass percentage content of P-glucan is 25%, the mass percentage content of ergothioneine is 0.009%, loss on drying is 4%, water-soluble extractive content is 46%;

[0088] Excipient: microcrystalline cellulose, food-grade raw material, no industrial-grade raw material added, only physical mixing with active ingredients, no chemical cross-linking reaction. Preparation method:

[0089] The preparation process of Agaricus bisporus extract, and the impurity removal, grinding, and sieving treatment of AKG, PQQ disodium salt, and microcrystalline cellulose are all the same as in Embodiment 1 ;

[0090] Put the pretreated raw materials into a three-dimensional motion mixer according to the weight ratio of 45:0.5:34.5:20, stirring speed and mixing environment parameters are consistent with Embodiment 1, stir until the material is uniformly mixed, obtaining the mixed material;

[0091] The operation steps and parameters for pre-sieving, tableting, crushing, sieving, and preliminary granulation are all the same as in Embodiment 1, obtaining preliminarily shaped granular material;

[0092] The drying equipment, temperature, time, and subsequent sieving operation are all the same as in Embodiment 1, obtaining the finished anti-aging composition with AKG-PQQ synergistically enhancing mitochondrial function.

[0093] Physicochemical index detection:

[0094] The finished product is a uniform brownish-yellow granule, with a particle size within the range of 8-30 mesh, no agglomeration, no discoloration; each active ingredient and microcrystalline cellulose are only in a physically mixed state, with no chemical cross-linking reaction occurring; the active ingredient retention rates of AKG, PQQ disodium salt, and Agaricus bisporus extract are 98.9%, 99.2%, and 98.8%, respectively.

[0095] Functional effect detection:

[0096] Select in vitro cultured senescent model hepatocytes, add the anti-aging composition of this embodiment, culture for 48 h, then detect the mitochondrial membrane potential. The results show that the fluorescence intensity of the hepatocyte mitochondrial membrane potential is at a relatively high level, indicating that the high proportion of 0-glucan and ergothioneine in the Agaricus bisporus extract potently maintains mitochondrial membrane integrity, the high proportion of PQQ disodium salt fully promotes mitochondrial biogenesis, and AKG continuously supplies metabolic substrate for mitochondrial function. The three act synergistically, stabilizing the potential difference across the mitochondrial membrane, efficiently maintaining the stability of the mitochondrial membrane potential, and ensuring mitochondrial electrochemical transmission function.

[0097] Select in vitro cultured senescent model hepatocytes, add the anti-aging composition of this embodiment, culture for 48 h, then detect the mitochondrial reactive oxygen species (ROS) level. The results show that the ROS content in mitochondria is significantly reduced. Because the high proportion of Agaricus bisporus extract provides abundant ergothioneine and 0-glucan, exerting a potent antioxidant effect, AKG reduces the generation of reactive oxygen species during mitochondrial metabolism, and PQQ disodium salt synergistically alleviates mitochondrial oxidative damage. The three, together with the good shaping and dispersion characteristics of microcrystalline cellulose, allow the active ingredients to act uniformly on mitochondria, greatly reducing the interference of oxidative damage on mitochondrial function and significantly enhancing the mitochondrial oxidative stress resistance.

[0098] Comparative Example:

[0099] The core component Agaricus bisporus extract is omitted, and the excipient adopts multiple complex forms. The rest of the preparation process is consistent with Embodiments 1, 2, and 3.

[0100] Raw material preparation (in parts by weight):

[0101] AKG: 52 parts;

[0102] PQQ disodium salt: 0.3 parts;

[0103] Excipient: 17.7 parts.

[0104] Raw material specifications:

[0105] The excipient is food-grade mannitol 8 parts + food-grade lactose 6 parts + food-grade magnesium stearate 3.7 parts. The raw material specifications of AKG, PQQ disodium salt, and the excipient are all consistent with the corresponding raw materials in Embodiments 1, 2, and 3, all being food-grade, with no industrial-grade raw material added.

[0106] Preparation method:

[0107] Completely consistent with the process steps and parameters of raw material pretreatment, ingredient mixing, material shaping, and drying treatment in Embodiments 1, 2, and 3.

[0108] Physicochemical index detection:

[0109] The finished product is a non-uniform light yellow granule, with about 30% of the particle size exceeding the 8-30 mesh limit range, with obvious slight agglomeration and localized discoloration; because the excipient is in multiple complex forms, non-specific physical adsorption occurs with AKG and PQQ disodium salt, not a simple physical mixing state; the active ingredient retention rates of AKG and PQQ disodium salt are 92.2% and 92.8% respectively, and the moisture content of the material after drying is 2.5%.

[0110] Functional effect detection:

[0111] Select the same in vitro cultured senescent model hepatocytes as in Embodiments 1, 2, and 3, under completely identical culture and detection conditions, add the anti-aging composition of this comparative example, culture for 48 h, then detect the mitochondrial membrane potential. The results show that the fluorescence intensity of the hepatocyte mitochondrial membrane potential is significantly lower, being only 65.2% of Embodiment 1, 58.7% of Embodiment 2, and 52.3% of Embodiment 3. Due to the absence of the core membrane protection component Agaricus bisporus extract, relying only on AKG's substrate supply and PQQ disodium salt's mitochondrial biogenesis effect cannot form a multi-dimensional synergistic regulatory system, making it difficult to stabilize the potential difference across the mitochondrial membrane, and the effect of maintaining the mitochondrial membrane potential is greatly reduced.

[0112] Under completely identical conditions as in Embodiments 1, 2, and 3, detecting the mitochondrial reactive oxygen species (ROS) level in hepatocytes shows that the ROS content in mitochondria is significantly increased, being 2.1 times that of Embodiment 1, 2.3 times that of Embodiment 2, and 2.5 times that of Embodiment 3. Because there is no antioxidant effect from ergothioneine and 0-glucan in the Agaricus bisporus extract, and the physical adsorption caused by the multiple complex excipients interferes with the normal function of AKG and PQQ disodium salt, it is neither able to effectively reduce the generation of ROS during mitochondrial metabolism nor alleviate the impact of oxidative damage on mitochondria, resulting in extremely poor mitochondrial oxidative stress resistance.

[0113] The above descriptions are only preferred embodiments of the present invention and are not intended to limit the present invention in any form. Although the present invention has been disclosed as 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, can make some changes or modifications to equivalent embodiments with equivalent changes using the above-disclosed technical content. 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

CLAIMS1. An anti-aging composition with AKG-PQQ synergistically enhancing mitochondrial function, characterized in that the composition comprises, in parts by weight:AKG: 40-65 parts;PQQ disodium salt: 0.05-0.5 parts;Agaricus bisporus extract: 15-35 parts;Excipient: 10-20 parts.

2. The anti-aging composition with AKG-PQQ synergistically enhancing mitochondrial function according to claim 1, characterized in that the AKG is 2-oxoglutaric acid, in an anhydrous crystal form, having a water solubility of not less than 100 g / L, and is not chemically modified.

3. The anti-aging composition with AKG-PQQ synergistically enhancing mitochondrial function according to claim 1, characterized in that the PQQ disodium salt is pyrroloquinoline quinone disodium salt, in the form of a white to pale yellow crystalline powder, readily soluble in water, having a residual solvent content of <0.001%.

4. The anti-aging composition with AKG-PQQ synergistically enhancing mitochondrial function according to claim 1, characterized in that the Agaricus bisporus extract is an extract obtained from Agaricus bisporus through a water extraction and alcohol precipitation process, the extraction raw material being fresh or dried Agaricus bisporus fruiting bodies, naturally containing 0-glucan and ergothioneine; wherein the Agaricus bisporus extract has a mass percentage content of 0-glucan of 10-30%, a mass percentage content of ergothioneine of 0.001-0.01%, a loss on drying of <5%, the extract being a light yellow to brownish powder, having a water-soluble extractive content of >40%.

5. The anti-aging composition with AKG-PQQ synergistically enhancing mitochondrial function according to claim 1, characterized in that the excipient is one selected from the group consisting of mannitol, lactose, microcrystalline icellulose, and magnesium stearate, and the excipient is a food-grade raw material.

6. An anti-aging composition with AKG-PQQ synergistically enhancing mitochondrial function, characterized in that the preparation method of the composition comprises:Raw material pretreatment: performing a water extraction and alcohol precipitation pretreatment process on Agaricus bisporus fruiting bodies to obtain the Agaricus bisporus extract, then respectively subjecting AKG, PQQ disodium salt, the Agaricus bisporus extract, and the excipient to pretreatment including impurity removal and grinding;Ingredient mixing: putting the pretreated AKG, PQQ disodium salt, Agaricus bisporus extract, and excipient into mixing equipment according to a predetermined proportion, and mixing with stirring to obtain a uniform mixed material;Material shaping: subjecting the mixed material to a shaping operation using a dry granulation process to obtain a preliminarily shaped material;Drying treatment: placing the preliminarily shaped material in drying equipment for a drying operation to remove free moisture, and processing the dried material to remove agglomerated material, thereby obtaining the finished composition.

7. The anti-aging composition with AKG-PQQ synergistically enhancing mitochondrial function according to claim 6, characterized in that, in the raw material pretreatment, the water extraction and alcohol precipitation pretreatment process for Agaricus bisporus fruiting bodies comprises: crushing the Agaricus bisporus fruiting bodies, adding water for extraction, then adding ethanol to adjust the alcohol concentration of the system, allowing to stand, centrifuging to obtain a precipitate, and drying the precipitate; wherein the solid-liquid ratio for water extraction is 1:8-15, the extraction temperature is 70-90°C, and the extraction time is 1-3 h; the alcohol concentration for alcoholprecipitation is 60-80%, the standing temperature is 4-10°C, the standing time is 8-16 h, the centrifugation speed is 3000-5000 r / min, and the centrifugation time is 10-20 min; impurity removal is performed using a vibrating screen, with a vibration frequency of the vibrating screen being 20-30 Hz; the grinding time is 5-15 min, the ground material is subjected to sieving treatment with a mesh size of 80-120 mesh, and coarse particles that do not pass through the sieve are removed, retaining only the uniform fine powder material.

8. The anti-aging composition with AKG-PQQ synergistically enhancing mitochondrial function according to claim 6, characterized in that, in the ingredient mixing, the proportion of AKG, PQQ disodium salt, Agaricus bisporus extract, and excipient is 40-65:0.05-0.5: 15-35: 10-20; the stirring speed of the mixing equipment is 100-300 r / min, the ambient temperature during the mixing process is 20-25°C, the ambient relative humidity is 40-60%, and stirring is continued until the material is uniformly mixed.

9. The anti-aging composition with AKG-PQQ synergistically enhancing mitochondrial function according to claim 6, characterized in that, in the material shaping, the dry granulation process comprises: subjecting the mixed material to pre-sieving using a 16-20 mesh screen, then feeding the pre-sieved material into a dry granulator for tableting, with a roller linear speed of 5-15 m / min and a granulation pressure of 5-15 MPa, to obtain a sheet-like material; then crushing the sheet-like material in the dry granulator, passing the crushed material through a 20-30 mesh screen, subjecting the sieved material to preliminary granulation, and after preliminary granulation, passing it through an 8-30 mesh screen, thereby completing the dry granulation and obtaining preliminarily shaped granular material.

10. The anti-aging composition with AKG-PQQ synergistically enhancing mitochondrial function according to claim 6, characterized in that, in the drying treatment, the drying temperature is 40-60 °C, the drying time is 2-6 h, and the moisture content after drying is 1-3%.

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