An anti-aging food-medicine formula and its preparation method

Abstract

This invention relates to the field of medical preparations technology, and more particularly to an anti-aging food-medicine homology formula and its preparation method. The formula uses Curcuma zedoaria as the principal ingredient, and is formulated with 18-35 parts of Curcuma longa, 8-20 parts of Lycium barbarum, and 3-10 parts of fresh ginger on a dry basis. Aloe vera and Curcuma aromatica can be added as needed. Isochuronidone and its C-8 epimer are used as the core efficacy markers, with their total mass percentage not less than 0.005%. This invention employs a biphasic extraction and microencapsulation process to solve the problem of easy degradation of volatile components in Curcuma zedoaria. Combined with a precise HPLC quality control method, experimental verification shows that this formula can exert anti-inflammatory, antioxidant, and anti-aging activities through multiple pathways, and has good safety for consumption. It can be used to prepare antioxidant and immune-enhancing foods, health foods, and related pharmaceutical preparations.

Description

Technical Field

[0001] This invention relates to the field of medical preparations technology, specifically to an anti-aging food-medicine formula and its preparation method. Background Technology

[0002] I. Core Pathophysiological Mechanisms of Aging Aging is considered to be associated with multiple factors, including oxidative stress, chronic low-grade inflammation, mitochondrial dysfunction, protein homeostasis imbalance, insufficient autophagy, metabolic imbalance, and immune decline. Among these factors, Nrf2 and NF-κB have a cross-regulatory relationship in the regulation of oxidative stress and inflammation, and their imbalance is closely related to various types of chronic degenerative changes.

[0003] II. Current Status of Research on Core Raw Materials in Formulas Research on turmeric: Curcumin has a wide range of antioxidant, anti-inflammatory and multi-pathway regulatory characteristics. It has been summarized in many reviews as being able to act on signaling axes such as Nrf2 / HO-1, NF-κB, and SIRT1 / AMPK. It is a common natural active substance in anti-aging research.

[0004] Research on wolfberry: Lycium barbarum polysaccharide (LBP) has been reported to improve stress tolerance and prolong lifespan in Caenorhabditis elegans and aged mice. It can also improve age-related oxidative damage and immune indicators, thus possessing the pharmacological activity basis related to anti-aging.

[0005] Related research: The rhizome is rich in volatile sesquiterpenes. Literature reports that furanodiene and furanodione, which have anti-inflammatory activities, can be isolated from the methanol extract of Curcumazedoaria rhizome. At the same time, sesquiterpenes have been summarized in many reviews as having potential for anti-inflammatory, antioxidant, and metabolic regulation effects, and their role in health maintenance related to anti-aging has been discussed by the academic community.

[0006] III. Deficiencies and Shortcomings of Existing Related Technologies There are already many patents related to "anti-aging compositions" in the existing technology. Common combinations include wolfberry extract and turmeric extract. However, most of these solutions have not established a systematic technical solution around "standardization of key components of turmeric sesquiterpenes + stabilization process + multi-model anti-aging evidence chain". As a result, there are problems such as unclear core active ingredients, poor quality controllability, and insufficient stability of active ingredients.

[0007] Existing technologies also include patented solutions that combine turmeric extract and zedoary extract for oral administration, but their intended use and technical features differ significantly from the core anti-aging objective of this invention, and they have not established a complete technical system and evidence chain for multi-target regulation related to aging.

[0008] Existing anti-aging technologies containing Curcuma zedoaria extract are mostly focused on the development of topical products. There is a significant gap in anti-aging system solutions with Curcuma zedoaria as the principal ingredient, which are suitable for oral / consumable scenarios and comply with the food / health food regulatory framework.

[0009] Therefore, in response to the above problems, a medicinal and edible formula for anti-aging and its preparation method are proposed. Summary of the Invention

[0010] The purpose of this invention is to provide an anti-aging medicinal and edible formula and its preparation method to solve the problems mentioned in the background art.

[0011] To achieve the above objectives, the present invention provides the following technical solution: (I) Anti-aging medicinal and edible homology formula composition The anti-aging medicinal and edible formula composition of the present invention comprises, on a dry basis, the following basic components: 40-60 parts of Curcuma zedoaria (P. rhizoma) powder and / or its extract, 18-35 parts of Curcuma longa powder and / or its extract, 5-25 parts of Lycium barbarum powder and / or its extract, and 1-15 parts of Zingiber officinale powder and / or its extract.

[0012] Furthermore, the composition of the present invention may include the following optional components to enhance efficacy: 0-15 parts by dry basis by weight of aloe vera gel powder and / or its polysaccharide extract; and / or 0-10 parts by dry basis by weight of berberine and / or berberine-containing plant extracts.

[0013] Furthermore, the composition of the present invention may be supplemented with 3 to 6 parts of Curcuma wenyujin rhizome powder and / or its extract to enhance the efficacy spectrum of volatile sesquiterpenes.

[0014] Furthermore, the composition contains isocurcuminone and / or its stereoisomers as core efficacy markers, and the total mass percentage of isocurcuminone and its stereoisomers is not less than 0.001% as determined by high performance liquid chromatography (HPLC) external standard method; the CAS number of isocurcuminone is 24268-42-6.

[0015] Furthermore, the turmeric extract is a mixture of turmeric volatile oil and turmeric alcohol extract; the turmeric extract is a turmeric ethanol extract, wherein curcumin accounts for no less than 10% by mass; the wolfberry extract is a wolfberry water-extracted polysaccharide extract, wherein wolfberry polysaccharide accounts for no less than 20% by mass; and the ginger extract is a ginger water extract or an alcohol extract.

[0016] Furthermore, the composition is an oral preparation, specifically any one of powder, granules, tablets, capsules, paste, or oral liquid.

[0017] (II) Preparation method of anti-aging medicinal and food homology formula composition This invention provides three industrially scalable preparation methods, which can be selected according to the target product's morphology and efficacy requirements, as follows: Method 1: Two-phase extraction + microcapsule refill preparation method (core preferred solution) This method is used to prepare standardized extract-type compositions, specifically including the following steps: a) Pretreatment of Curcuma zedoaria: Curcuma zedoaria raw materials are cleaned, dried at low temperature, pulverized and passed through an 80-120 mesh sieve, and the volatile oil is collected by steam distillation in a closed condensation system. The residue after distillation is reserved for later use; b) Preparation of Curcuma zedoaria extract: The residue from step a) is extracted with a 50%-70% (v / v) ethanol aqueous solution at ≤60℃ by low-temperature reflux or ultrasonic extraction. The extracts are combined and concentrated under reduced pressure to obtain Curcuma zedoaria extract; c) Stabilization treatment of volatile oil: The volatile oil of Curcuma zedoaria collected in step a) is stabilized using β-coated ethanol. - Microencapsulation is performed using either cyclodextrin inclusion technology or maltodextrin-gum arabic composite spray drying technology to obtain volatile oil microcapsule powder; d) Preparation of excipient extracts: Turmeric extract is prepared by ethanol extraction from turmeric raw material, Lycium barbarum polysaccharide extract is prepared by water extraction and alcohol precipitation from Lycium barbarum raw material, and ginger extract is prepared from ginger raw material; e) Mixing and molding: The Curcuma zedoaria extract from step b), the volatile oil microcapsule powder from step c), and the extracts from step d) are mixed according to the aforementioned ratio, spray dried, and then granulated, tableted, capsule filled, or sterilized and filled to obtain the finished product.

[0018] Method 2: Preparation method using raw material grinding and direct mixing This method is used to prepare raw material powder composition, specifically including the following steps: (1) After cleaning and removing impurities, each raw material is dried at a low temperature of ≤60℃ and pulverized through an 80~120 mesh sieve to obtain fine powder of each raw material; (2) Weigh each raw material fine powder according to the aforementioned ratio, and mix them for 10~20 minutes using a V-type mixer to obtain mixed powder; (3) After the mixed powder is sieved and granulated and tested for metal foreign matter, it is packaged in a light-proof aluminum foil composite bag or a light-proof container with nitrogen filling to obtain substitute tea or solid beverage finished products.

[0019] Method 3: Decoction and Concentration Preparation Method This method is used to prepare liquid preparations or ointments, and specifically includes the following steps: (1) Weigh each raw material according to the above ratio, add 8 to 12 times the amount of purified water after feeding, decoct twice, each time for 45 to 60 minutes; (2) Combine the two decoctions, filter and concentrate under reduced pressure, and control the relative density of the concentrate to the specified range; (3) After sterilization, the concentrate is bottled to obtain oral liquid or plant beverage finished product; or the concentrate is further concentrated to a thick paste, and excipients are added and mixed to make ointment to obtain ointment finished product.

[0020] (III) Application of Anti-aging Food-Medicine Homologous Formula Combinations The composition described in this invention can be used to prepare food or health food that enhances the body's antioxidant capacity, maintains immune homeostasis, improves oxidative stress-related health status, and improves age-related physical strength and energy status; it can also be used to prepare pharmaceutical preparations that delay age-related degenerative changes in physiological functions.

[0021] Furthermore, the dosage form of the food / health food is any one of the following: herbal tea, solid beverage, compressed candy, oral liquid, or herbal paste; the dosage form of the pharmaceutical preparation is any one of the following: tablet, capsule, granule, or oral liquid.

[0022] Compared with the prior art, the beneficial effects of the present invention are: 1. In this invention, Curcuma zedoaria is used as the principal herb, with its volatile sesquiterpenes such as isocurcuminone as the core active substances. It is combined with Curcuma longa, Lycium barbarum, and Zingiber officinale to form a principal-assistant-adjuvant system. Through the synergistic effect of multiple pathways such as "anti-inflammatory-antioxidant-metabolic regulation-immune support-barrier repair", it simultaneously regulates the core signaling pathways related to aging, such as the NF-κB / MAPK inflammatory axis, the Nrf2 / HO-1 antioxidant axis, and the AMPK / SIRT1 / autophagy axis. This breaks through the limitations of existing compositions that target only a single point and can only achieve single antioxidant or immune regulation, and realizes a systematic intervention on multiple aspects of aging.

[0023] 2. In this invention, addressing the industry pain point that the volatile sesquiterpenes of Curcuma zedoaria are easily volatile and easily oxidized and degraded, a pioneering two-phase extraction and stabilization process of "distillation-low temperature extraction-microcapsule re-addition" is proposed. The volatile active ingredients are collected and protected separately by steam distillation, and then added back to the extract system after being encapsulated in microcapsules. At the same time, the low temperature extraction is used to avoid the degradation of heat-sensitive components. This can increase the retention rate of core sesquiterpenes such as curcuminone in the final product by more than 80% in the 6-month accelerated test, which greatly improves the storage stability and efficacy consistency of the product.

[0024] 3. In this invention, the core efficacy markers are precisely defined by CAS number, chemical structure, and detection method, avoiding ambiguity in component naming and non-reproducible detection problems. A matching HPLC simultaneous determination method is established, which can simultaneously quantitatively detect sesquiterpenes, curcumin, and berberine in Curcuma zedoaria. The content of Lycium barbarum polysaccharides is controlled by the phenol-sulfuric acid method. At the same time, a finished product fingerprint spectrum quality control standard is established, which can effectively ensure batch-to-batch consistency of products and meet the quality control requirements of industrial production and registration application. Attached Figure Description

[0025] Figure 1 This is a schematic diagram of the overall structure of the present invention. Detailed Implementation

[0026] The technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0027] It should be noted that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to limit the exemplary embodiments according to this application. As used herein, the singular form is intended to include the plural form as well, unless the context clearly indicates otherwise. Furthermore, it should be understood that when the terms "comprising" and / or "including" are used in this specification, they indicate the presence of features, steps, operations, devices, components, and / or combinations thereof.

[0028] Please see Figure 1 The present invention provides a technical solution: I. Experimental Materials, Reagents and Instruments (a) Raw materials and reagents Curcuma zedoaria: The dried rhizome of Curcuma zedoaria (Curcuma phaeocaulis Val.) from the Guangxi authentic producing area was selected, which meets the relevant quality requirements of Part I of the 2025 edition of the Chinese Pharmacopoeia, with a volatile oil content of ≥1.5% (ml / g). Turmeric: The dried rhizomes of turmeric (Curcuma longa L.) from the authentic producing area of ​​Qianwei, Sichuan Province, are selected, meeting the relevant requirements of the 2025 edition of the Chinese Pharmacopoeia, Part I, and the National Health Commission's Food and Drug Quality Catalogue, with a curcumin content ≥1.0%; Goji berries: Selected dried, ripe Ningxia goji berries (Lycium barbarum L.) from the Ningxia Zhongning traditional producing area, meeting the relevant requirements of the 2025 edition of the Chinese Pharmacopoeia, with a goji berry polysaccharide content ≥3.0%; Ginger: The dried rhizomes of ginger (Zingiber officinale Rosc.) from the authentic producing area of ​​Laiwu, Shandong Province, are selected and meet the relevant requirements of the 2025 edition of the Chinese Pharmacopoeia, Part I and the Food and Drug Substances Catalogue. Curcuma wenyujin: The dried rhizome of Curcuma wenyujin Y.H.Chenet C.Ling from the traditional producing area of ​​Ruian, Zhejiang Province, is selected, meeting the relevant requirements of Part I of the 2025 edition of the Chinese Pharmacopoeia; Curacao aloe vera gel freeze-dried powder: commercially available food grade, meeting the requirements of the National Health Commission's announcement on new resource foods, with aloe polysaccharide content ≥10.0% and anthraquinone substances ≤10mg / kg; Berberine hydrochloride: Commercially available pharmaceutical grade, purity ≥98.0%, meeting the relevant requirements of the 2025 edition of the Chinese Pharmacopoeia, Part II; Isorhodotoranone reference standard (CAS24268-42-6), curcumin reference standard, berberine hydrochloride reference standard: provided by the National Institutes for Food and Drug Control, purity ≥98.0%; Ethanol and acetonitrile were of chromatographic grade, all other reagents were of analytical grade, and the water used in the experiment was ultrapure water.

[0029] (ii) Test instruments High-performance liquid chromatograph (Agilent 1260), ultraviolet-visible spectrophotometer (Shimadzu UV-2600), steam distillation apparatus, low-temperature reflux extraction apparatus, vacuum concentration tank, spray dryer, V-type mixer, β-cyclodextrin inclusion tank, high-pressure homogenizer, constant temperature and humidity accelerated test chamber, clean bench, enzyme reader, real-time fluorescence quantitative PCR instrument.

[0030] II. Composition Formulation Examples In the following examples, the composition formulations are all based on dry weight, and the recommended daily intake for adults is 30g / day, divided into two doses after meals, which complies with the compliance limits for food and drug substances and new resource foods.

[0031] Example 1: Simplified Basic Composition (Food Compliant Version) The composition of this embodiment contains only the basic components of the principal, assistant, adjuvant, and guide herbs, with no optional added ingredients. It fully complies with the management requirements of the food and drug substance catalog and can be directly developed into a general food. The specific formula is: 50 parts of Curcuma zedoaria powder, 30 parts of Curcuma longa powder, 10 parts of Lycium barbarum powder, and 10 parts of fresh ginger powder.

[0032] Example 2: Full Formulation Enhanced Composition The composition of this embodiment contains all optional enhancing components and can be used in the development of health foods or pharmaceutical preparations. The specific formula is as follows: 40 parts of Curcuma zedoaria extract, 30 parts of Curcuma longa extract, 15 parts of Lycium barbarum extract, 5 parts of Zingiber officinale extract, 5 parts of Aloe vera gel freeze-dried powder, and 5 parts of berberine hydrochloride.

[0033] Example 3: Sesquiterpene Enhanced Composition In this embodiment, the composition is enhanced by adding Curcuma aromatica to enhance the efficacy spectrum of volatile sesquiterpenes. The specific formula is as follows: 40 parts Curcuma zedoaria powder, 30 parts Curcuma longa powder, 15 parts Curcuma aromatica powder, 10 parts Lycium barbarum powder, and 5 parts fresh ginger powder.

[0034] Example 4 Preferred Fixed Formulation B (Food-Grade Simplified Formulation) This embodiment is a simplified version of the solidified formula, suitable for the development of substitute tea and solid beverage. The specific formula is: 50 parts of Curcuma zedoaria powder, 30 parts of Curcuma longa powder, 10 parts of Lycium barbarum powder, and 10 parts of fresh ginger powder (corresponding to 30g of daily dry base: 15g of Curcuma zedoaria, 9g of Curcuma longa, 3g of Lycium barbarum, and 3g of fresh ginger).

[0035] Example 5: Preferred Fixed Formula A (All-Effect Formula) This embodiment is a solidified complete formula suitable for the development of health food products. The specific formula is as follows: 40 parts of Curcuma zedoaria powder, 30 parts of Curcuma longa powder, 15 parts of Lycium barbarum powder, 5 parts of fresh ginger powder, 5 parts of freeze-dried Aloe vera gel powder, and 5 parts of berberine hydrochloride (corresponding to 30g of dry base per day: 12g of Curcuma zedoaria, 9g of Curcuma longa, 4.5g of Lycium barbarum, 1.5g of fresh ginger, 1.5g of freeze-dried Aloe vera gel powder, and 1.5g of berberine hydrochloride).

[0036] III. Examples of Composition Preparation Methods Example 6: Raw material grinding and direct mixing preparation process This embodiment is suitable for substitute tea, solid beverage, and powder products. The specific steps are as follows: (1) Raw material pretreatment: Take turmeric, turmeric, wolfberry and ginger raw materials, remove impurities and non-medicinal parts after cleaning, place them in a hot air circulating oven at ≤60℃ for low temperature drying, and control the raw material moisture content to ≤10.0%; crush the dried raw materials separately, pass them through a 100-mesh sieve to obtain fine powder of each raw material, and set aside; (2) Weighing and mixing: According to the formula ratio of Example 1, accurately weigh each raw material fine powder, put it into a V-type mixer, mix for 15 minutes until the mixing uniformity RSD≤5.0%; (3) Post-processing: After mixing, pass the 80-mesh sieve for granulation, and after passing the metal foreign object detection, use aluminum foil composite bags to avoid light and fill with nitrogen for packaging, with a net content of 15g per bag, to obtain the finished substitute tea / solid beverage.

[0037] Example 7: Biphasic Extraction + Microcapsule Refill Preparation Process (Core Optimized Process) This embodiment is the core recommended process, which can maximize the retention of the volatile sesquiterpenes and curcumin activity of Curcuma zedoaria, and is suitable for standardized extract-type granules, tablets and capsules. The specific steps are as follows: (1) Collection and extraction of Curcuma zedoaria volatile oil: Take Curcuma zedoaria slices, crush them through a 20-mesh sieve, add 10 times the amount of purified water, steam distill for 4 hours, and collect the volatile oil by condensation in a sealed container and refrigerate for later use; drain the Curcuma zedoaria residue after distillation, add 6 times the amount of 60% ethanol aqueous solution, and reflux extract twice at 55℃ for 1 hour each time, and combine the extracts. The extracts were filtered and concentrated under reduced pressure to a clear paste with a relative density of 1.10~1.15 at 60℃, and set aside for use; (2) Microencapsulation of volatile oil: Take the volatile oil of Curcuma zedoaria collected in step (1), add saturated aqueous solution of β-cyclodextrin at a mass ratio of volatile oil to β-cyclodextrin of 1:8, stir and encapsulate for 2 hours at 45℃ and 300r / min, refrigerate and stand for 12 hours, filter, precipitate and dry at low temperature, pulverize and pass through an 80-mesh sieve to obtain microcapsule powder of Curcuma zedoaria volatile oil, set aside for use; (3) Preparation of excipient extract: Preparation of turmeric extract: Take turmeric slices, crush them through a 20-mesh sieve, add 8 times the volume of 70% ethanol aqueous solution, reflux extract twice, 1.5h each time, combine the extracts, filter, concentrate under reduced pressure, and spray dry to obtain turmeric extract with curcumin content ≥20%, for later use. Preparation of Lycium barbarum extract: Take Lycium barbarum slices, add 10 times the amount of purified water, and extract twice at 90℃ for 2 hours each time. Combine the extracts, filter, and concentrate under reduced pressure to a clear extract with a relative density of 1.08~1.10. Add ethanol to a concentration of 70% for alcohol precipitation, refrigerate at 4℃ for 24 hours, take the supernatant to recover the ethanol, concentrate under reduced pressure, and spray dry to obtain Lycium barbarum extract with a polysaccharide content ≥40%, for later use. Preparation of ginger extract: Take ginger slices, add 8 times the amount of purified water, collect volatile oil by steam distillation, extract the residue twice with water, combine the water extracts and concentrate, mix with volatile oil and spray dry to obtain ginger extract for later use; (4) Mixing and molding: Mix the Curcuma zedoaria extract from step (1), the volatile oil microcapsule powder from step (2), and the extracts of each excipient from step (3) according to the formula ratio of Example 2, add an appropriate amount of maltodextrin excipient, spray dry to make dry extract powder, after granulation and granulation, the dry extract powder can be directly packaged into granules, or compressed into tablets, or filled into hard capsules to make capsule finished products.

[0038] Example 8: Preparation process of decoction-concentrated type This embodiment is suitable for oral liquids, herbal beverages, and herbal pastes. The specific steps are as follows: (1) Adding and decocting: Weigh each raw material slice according to the formula ratio of Example 1, clean and select them, put them into a multi-functional extraction tank, add 10 times the amount of purified water, soak for 30 minutes, and decoct twice, each time for 60 minutes; (2) Concentration and filtration: Combine the two decoctions, filter with a 200-mesh filter cloth, concentrate the filtrate under reduced pressure to a clear paste with a relative density of 1.05~1.10 at 60℃, and then filter again with a 300-mesh filter cloth to obtain a concentrated liquid; (3) Preparation of finished product: Oral liquid preparation: Take the above concentrated liquid, add appropriate amount of white sugar and potassium sorbate for flavoring and preservation, adjust the volume to the specified volume, stir evenly, sterilize by UHT instantaneous sterilization, fill into 10ml brown oral liquid bottles, sterilize and check for leaks to obtain the finished oral liquid. Preparation of the paste: Take the above concentrated liquid and continue to concentrate it under reduced pressure until it becomes a thick paste with a relative density of 1.25~1.30 at 60℃. Add refined honey and rice wine, stir evenly, heat to reduce the paste, cool and then package it into brown paste bottles to obtain the finished paste.

[0039] IV. Quality Control and Stability Test Examples Example 9: Determination of the content of the core active ingredient in the composition This embodiment establishes a standardized quality control method for the composition, and performs quantitative detection of core markers, as detailed below: (1) Simultaneous determination of the contents of isocurcumin, curcumin and berberine by HPLC Chromatographic conditions: Agilent C18 column (250 mm × 4.6 mm, 5 μm); mobile phase: acetonitrile (phase A) - 0.1% formic acid aqueous solution (phase B); gradient elution program: 0–10 min, 20% A → 40% A; 10–25 min, 40% A → 60% A; 25–35 min, 60% A → 90% A; 35–40 min, 90% A → 20% A; flow rate: 1.0 mL / min; column temperature: 30 °C; detection wavelengths: 230 nm (isocurcumin), 420 nm (curcumin), 345 nm (berberine); injection volume: 10 μL.

[0040] Sample preparation: Weigh approximately 1.0 g of the powder accurately and place it in a stoppered conical flask. Accurately add 25 ml of 70% methanol, seal tightly, weigh, and extract ultrasonically for 30 min (power 250 W, frequency 40 kHz). Cool, weigh again, and replenish the lost weight with 70% methanol. Shake well, centrifuge, and filter the supernatant through a 0.22 μm organic phase filter membrane to obtain the test solution.

[0041] Determination method: Accurately pipette 10 μl of the reference solution and the test solution into the liquid chromatograph, and calculate the content according to the external standard method.

[0042] Limit requirements: In the finished product, the total content of isocurcumin and its stereoisomers shall be ≥0.005%, the curcumin content shall be ≥0.10%, and the berberine hydrochloride content in the finished product containing berberine shall be 90.0%~110.0% of the labeled amount.

[0043] (2) Determination of Lycium barbarum polysaccharide content by phenol-sulfuric acid method Preparation of standard curve: Accurately weigh an appropriate amount of glucose reference standard dried to constant weight at 105℃, add water to prepare a solution containing 0.1 mg per ml, thus obtaining the reference solution. Accurately measure 0.2, 0.4, 0.6, 0.8, and 1.0 ml of the reference solution and place them in stoppered test tubes respectively. Add water to 1.0 ml, accurately add 1.0 ml of 5% phenol solution, shake well, quickly add 5.0 ml of sulfuric acid, shake well, heat in a boiling water bath for 15 min, remove, and cool in an ice-water bath for 5 min. Using the corresponding reagent as a blank, measure the absorbance at a wavelength of 490 nm. Plot the standard curve with absorbance as the ordinate and glucose concentration as the abscissa.

[0044] Sample preparation: Weigh approximately 2.0 g of the powder accurately, add 100 ml of petroleum ether (60-90℃), heat under reflux for 1 h, discard the petroleum ether solution, evaporate the residue to dryness, add 100 ml of 80% ethanol, heat under reflux for 1 h, filter, discard the filtrate, place the residue along with the filter paper in a flask, add 150 ml of water, heat under reflux for 2 h, filter while hot, wash the container and residue with a small amount of hot water, add the washings to the filtrate, cool, transfer to a 250 ml volumetric flask, add water to the mark, shake well, and the test solution is obtained.

[0045] Determination method: Accurately measure 1.0 ml of the test solution, and according to the method under the preparation of standard curve, starting from "accurately add 1.0 ml of 5% phenol solution", determine the absorbance according to the method, read the glucose content in the test solution from the standard curve, and calculate to obtain the result.

[0046] Limit requirement: The content of wolfberry polysaccharides in the finished product (calculated as glucose equivalent) is ≥0.50%.

[0047] Example 10 Composition Stability Test The capsules prepared in Example 7 were sealed in aluminum-plastic blister packs and aluminum foil bags for stability testing, as detailed below: Accelerated stability test: The samples were placed in a constant temperature and humidity chamber and stored at 40℃±2℃ and 75%±5% relative humidity for 6 months. Samples were taken at 0, 1, 3 and 6 months respectively, and the core indicators were tested according to the method of Example 9. At the same time, the properties, moisture, microbial limit and peroxide value were examined.

[0048] Long-term stability test: The sample was placed in a constant temperature and humidity chamber and kept at 25℃±2℃ and relative humidity of 60%±10% for 24 months. Samples were taken at 0, 3, 6, 12, 18 and 24 months to test the above indicators.

[0049] Test results: After 6 months of accelerated testing and 24 months of long-term testing, the product's properties showed no significant changes, and the moisture content, microbial limits, and peroxide value all met the standard requirements. The content retention rate of isocurcumin furandienone was ≥85%, and the content retention rate of curcumin was ≥80%, indicating that the process of this invention can significantly improve the storage stability of the core active ingredients and solve the technical problems of easy volatility and easy oxidative degradation of volatile sesquiterpenes in Curcuma zedoaria.

[0050] V. Examples of Pharmacological Activity Validation of the Composition Example 11: Validation of in vitro anti-inflammatory and antioxidant activities Experimental groups: a blank control group, a model control group, low / medium / high dose groups of the composition of the present invention (extracts prepared in Example 2, with final concentrations of 25 μg / ml, 50 μg / ml, and 100 μg / ml, respectively), and a positive control group (curcumin, with a final concentration of 50 μmol / L).

[0051] Anti-inflammatory activity assay: Using a RAW264.7 macrophage model, an inflammation model was induced by LPS. After 24 hours of drug intervention, the levels of IL-6 and TNF-α inflammatory factors in the cell supernatant were detected by ELISA, and the phosphorylation level of NF-κBp65 protein was detected by Western Blot.

[0052] Antioxidant activity assay: Using the HDF human skin fibroblast model, an oxidative damage model was induced by H2O2. After 24 hours of drug intervention, the intracellular ROS and MDA content, as well as the activities of SOD and CAT antioxidant enzymes, were detected. The nuclear translocation of Nrf2 was observed using a fluorescence microscope.

[0053] Experimental results: Compared with the model control group, each dose group of the composition of the present invention can significantly reduce the secretion levels of IL-6 and TNF-α in RAW264.7 cells induced by LPS (p<0.05, p<0.01), and inhibit the phosphorylation of NF-κBp65 protein; it can significantly reduce the content of ROS and MDA in HDF cells, and increase the activity of SOD and CAT (p<0.05, p<0.01), and promote Nrf2 nuclear translocation, and shows obvious dose dependence, which confirms that the composition of the present invention has significant in vitro anti-inflammatory and antioxidant activities.

[0054] Example 12: Lifespan and Healthy Lifespan of Caenorhabditis elegans Experimental materials: Wild-type N2 Caenorhabditis elegans and Escherichia coli OP50 were selected as food sources.

[0055] Experimental groups: A blank control group, low / medium / high dose groups of the composition of the present invention (final concentrations of culture medium were 100 μg / ml, 200 μg / ml, and 400 μg / ml, respectively), and a positive control group (resveratrol, final concentration 100 μmol / L) were set up. Each group had 3 parallel plates, and each plate was inoculated with about 100 nematodes.

[0056] Lifetime test: After nematodes were synchronized to the L4 stage, the drug was administered and cultured at a constant temperature of 20°C. The number of surviving nematodes was counted every 2 days and transferred to fresh drug-containing plates until all nematodes died. Survival curves were plotted and the average lifetime and maximum lifetime were calculated.

[0057] Healthy lifespan indicators: The motility, swallowing frequency, and survival rates under heat stress and oxidative stress of nematodes were measured. The mRNA expression levels of lifespan-related genes daf-16, sir-2.1, and skn-1 were detected by qPCR.

[0058] Experimental results: Compared with the blank control group, the medium and high dose groups of the composition of the present invention can significantly prolong the average lifespan and maximum lifespan of Caenorhabditis elegans (p<0.05, p<0.01), improve the motility and swallowing frequency of nematodes, and enhance the survival rate under heat stress and oxidative stress. At the same time, it can significantly upregulate the expression of longevity-related genes such as daf-16, sir-2.1, and skn-1, confirming that the composition of the present invention has the activity of prolonging the lifespan of nematodes and improving healthy lifespan.

[0059] Example 13 Validation of Anti-aging Related Indicators in Mice Experimental animals: SPF-grade ICR aged male mice, 12 months old, weighing 38±2g, were randomly divided into aged control group, low / medium / high dose group of the composition of the present invention (gavage dose of 1g / kg / d, 2g / kg / d, and 4g / kg / d, respectively), positive control group (metformin, 200mg / kg / d), and a 6-month-old young control group. Each group consisted of 12 mice, and the drugs were administered by gavage for 12 consecutive weeks.

[0060] Detection indicators: After the experiment, the activities of SOD, CAT, and GSH-Px antioxidant enzymes and the content of MDA in mouse serum were detected. The serum levels of IL-6 and TNF-α inflammatory factors were detected by ELISA. Fasting blood glucose and insulin levels in mice were detected, and the insulin resistance index was calculated. The Morris water maze test was used to detect the cognitive ability of mice. HE staining was used to observe the pathological changes in the liver and kidney tissues of mice.

[0061] Experimental results: Compared with the aged control group, the composition of the present invention at each dosage group significantly increased the activity of serum antioxidant enzymes in aged mice and reduced the levels of MDA, IL-6, and TNF-α (p<0.05, p<0.01); improved insulin resistance and glucose tolerance in mice; significantly shortened the escape latency in the water maze and increased the number of times mice crossed platforms (p<0.05); and improved the degenerative pathological changes in the liver and kidneys of aged mice, confirming that the composition of the present invention can improve aging-related physiological indicators in aged mice and has in vivo anti-aging activity.

[0062] VI. Examples of Composition Safety Evaluation Example 14 Acute Toxicity Test in Mice Twenty SPF-grade ICR mice (half male and half female) were randomly divided into a control group and a treatment group, with ten mice in each group. The treatment group received a single oral gavage dose of the composition of this invention at the maximum concentration and maximum administration volume (20 g / kg body weight), while the control group received an equal volume of purified water. The mice were observed for 14 consecutive days, and their general condition, weight changes, diet, symptoms of poisoning, and mortality were recorded. After the experiment, the mice were dissected to observe the morphology of major organs. Results: During the 14-day observation period, all mice survived without obvious symptoms of poisoning, and their weight and diet remained normal. Dissection revealed no visible abnormalities in major organs such as the heart, liver, spleen, lungs, and kidneys, indicating that the composition of this invention has no acute toxicity when taken orally and is highly safe for consumption.

[0063] Example 15: Repeated oral toxicity test in rats over 90 days Eighty SPF-grade SD rats, half male and half female, were randomly divided into a control group and low / medium / high dose groups of the composition of this invention (gavage doses of 1 g / kg / d, 3 g / kg / d, and 9 g / kg / d, respectively), with 20 rats in each group. The rats were administered the composition via gavage for 90 consecutive days. During the experiment, the rats' general condition, body weight, and food intake were observed and recorded weekly. After the administration, the rats' complete blood count and blood biochemistry (liver and kidney function, blood lipids, and blood glucose) were measured. The rats were dissected, and the coefficients of major organs were calculated. Histopathological examination was performed. Results: During the 90-day administration period, no rats in any dose group died or showed abnormal toxic symptoms. There were no significant differences in body weight and food intake compared to the control group. All complete blood count and blood biochemistry indicators were within the normal physiological range and showed no significant differences compared to the control group. There were no abnormal changes in the coefficients of major organs, and no obvious pathological damage was observed in the heart, liver, spleen, lungs, kidneys, gastrointestinal tract, and other tissues. This indicates that the composition of this invention has no significant toxicity when taken orally for a long period within the experimental dose range and has good food safety.

[0064] VII. Adaptation Examples for Different Dosage Forms Example 16: Compressed Candy (Ordinary Food) According to the formula of Example 1, take the fine powder of each raw material, add 30% maltodextrin and 2% magnesium stearate, mix evenly, and then compress into tablets using a single punch tablet press. The tablet weight is 1.0g / tablet, which is the finished compressed candy product. The recommended daily intake is 30 tablets, divided into 2 servings.

[0065] Example 17 Hard Capsules (Health Food / Pharmaceutical) The dry extract powder prepared according to Example 7 was filled into No. 0 hard capsules, with each capsule containing 0.3g, to obtain the finished hard capsule product. The recommended daily dosage is 10 capsules, divided into 2 doses.

[0066] Example 18: Plant-based beverage (common food) The concentrate was prepared according to the method in Example 8, purified water was added to make up the volume, and appropriate amounts of erythritol and citric acid were added for flavoring. After sterilization and filling, a 250ml / bottle plant beverage product was made. One bottle is consumed daily, which meets the regulatory requirement that the daily intake of aloe vera gel should be ≤30g.

[0067] Although embodiments of the invention have been shown and described, it will be understood by those skilled in the art that various changes, modifications, substitutions and alterations can be made to these embodiments without departing from the principles and spirit of the invention, the scope of which is defined by the appended claims and their equivalents.

Claims

1. An anti-aging formula derived from both food and medicine, characterized in that, Based on dry weight, it includes: 40-60 parts of Curcuma zedoaria powder and / or its extract, wherein the Curcuma zedoaria extract contains Curcuma zedoaria volatile oil microcapsule powder and Curcuma zedoaria alcohol extract; 18-35 parts of turmeric powder and / or its ethanol extract; 8-20 parts of wolfberry powder and / or its aqueous polysaccharide extract; 3-10 parts ginger powder and / or its extract; The formula contains isofuranodienone (CAS24268-42-6) and / or its C-8 epimer, furandienone, and the total mass percentage of the two is not less than 0.005% (w / w), as determined by HPLC external standard method.

2. The anti-aging food-medicine homology formula according to claim 1, characterized in that, Based on dry weight, it also includes 2 to 12 parts of aloe vera gel powder and / or its polysaccharide extract; and the daily intake of the formula, based on dry aloe vera gel, shall not exceed 1.5g.

3. The anti-aging food-medicine homology formula according to claim 1 or 2, characterized in that, Based on dry weight, it also includes 3 to 6 parts of Curcuma wenyujin powder and / or its extract; The mass ratio of Curcuma aromatica to Curcuma zedoaria is 1:6.67 to 1:

20.

4. The anti-aging food-medicine formula according to any one of claims 1-3, characterized in that, The formula is an oral solid dosage form, selected from powder, granules, tablets or capsules; the moisture content of the oral solid dosage form is ≤7%, and it is packaged in a light-proof and oxygen-barrier manner.

5. The anti-aging food-medicine formula according to any one of claims 1-4, characterized in that, The total mass percentage of the iso-curcuminone and / or its C-8 epimer is 0.005%~0.5% (w / w); and after 6 months of accelerated testing at 40℃±2℃ / 75%RH±5%RH, the content retention rate of the marker is not less than 80%.

6. A method for preparing the anti-aging medicinal and edible formula according to any one of claims 1-4, characterized in that, Includes the following steps: a) Clean and dry the raw material of Curcuma zedoaria to a moisture content of ≤10%, pulverize it through an 80-100 mesh sieve, and place it in a steam distillation apparatus. Distill it at atmospheric pressure and 100℃-105℃ for 2-4 hours. Collect the volatile oil of Curcuma zedoaria by sealing and condensing. Encapsulate the volatile oil with β-cyclodextrin at a core material:wall material mass ratio of 1:4-1:8, at an encapsulation temperature of 40℃-60℃ and a stirring time of 1-3 hours. After standing and refrigerating for 12-24 hours, filter and dry to obtain volatile oil microcapsule powder. b) The residue from distillation in step a) was extracted twice with an ethanol aqueous solution of 55%~65% by volume as the extraction solvent at a temperature of 45℃~55℃ and a material-to-liquid ratio of 1:8~1:12 (g / mL), for 1~2 hours each time. The extracts were combined and concentrated under reduced pressure at 50℃~60℃ to a relative density of 1.10~1.20 (measured at 60℃) to obtain Curcuma zedoaria ethanol extract. c) Take turmeric, wolfberry, and ginger raw materials separately, and prepare extracts according to the following methods: Turmeric extract: Using 70%~80% ethanol aqueous solution as the extraction solvent, extract twice at a temperature of 50℃~60℃ and a material-to-liquid ratio of 1:6~1:10 (g / mL), each time for 1~1.5 hours. Combine the extracts, concentrate under reduced pressure, and spray dry. Lycium barbarum polysaccharide extract: using pure water as the extraction solvent, extract twice at a temperature of 80℃~90℃ and a material-to-liquid ratio of 1:10~1:15 (g / mL), each time for 1.5~2 hours. Combine the extracts, concentrate them, add ethanol to a concentration of 60%~70% (v / v), precipitate alcohol, let stand for 12~24 hours, and dry the precipitate. Ginger extract: Use 50%~60% ethanol aqueous solution as extraction solvent, extract 1~2 times at 50℃~60℃, combine the extracts, concentrate under reduced pressure and dry. d) The volatile oil microcapsule powder obtained in step a), the turmeric alcohol extract obtained in step b), and the extracts obtained in step c) are mixed in the proportions described in claims 1 to 4, and then dried, granulated, tableted, or capsuled to obtain the finished product.

7. The method for preparing an anti-aging food-medicine homology formula according to claim 6, characterized in that, Before the inclusion of β-cyclodextrin in step a), the volatile oil of Curcuma zedoaria is mixed and dissolved with anhydrous ethanol at a volume ratio of 1:1 to 1:3; the encapsulation rate of the microcapsule powder is ≥75%, and the volatile oil retention rate is ≥70% after 6 months of accelerated testing.

8. The method for preparing an anti-aging food-medicine homology formula according to claim 6 or 7, characterized in that, Before step d), the method also includes an HPLC content determination step for each extract and the finished product: The chromatographic column was a C18 column (250 mm × 4.6 mm, 5 μm); The mobile phase was acetonitrile (A) - 0.1% formic acid aqueous solution (B), with gradient elution: 0~5 min, 30% A; 5~25 min, 30%~75% A; 25~35 min, 75%~95% A; 35~40 min, 95% A; Detection wavelengths: curcumin 420nm, isocurcumin furandienone and / or its C-8 epimer 230nm; Flow rate 1.0 mL / min; column temperature 30 °C; injection volume 10 μL; The reference standards were isocurcumin (CAS24268-42-6, purity ≥98%) and curcumin; The total content of isocurcumin and / or its C-8 epimer in the finished product is ≥0.005% (w / w), and the curcumin content is ≥0.1% (w / w).

9. The use of the anti-aging medicinal and edible formula according to any one of claims 1-4 in the preparation of food or health food for enhancing the body's antioxidant capacity.

10. The use of the anti-aging medicinal and edible formula according to any one of claims 1 to 4 in the preparation of health food for enhancing immunity or relieving physical fatigue.

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