Formula for repairing and improving ovarian aging and preparation process

Abstract

The invention relates to a formula and a preparation process for repairing and improving ovarian aging. The preparation process comprises the following steps: S1, screening and pretreating raw materials; s2, extracting active ingredients; s3, refining and purifying the extracting solution; s4, compounding formula components; according to the formula and the preparation process for repairing and improving ovarian aging, various natural active ingredients with definite pharmacological effects are scientifically matched, and an advanced dynamic circulating countercurrent extraction technology and a multistage membrane separation and purification process are adopted; systematic intervention on ovarian aging-related oxidative stress, mitochondrial dysfunction, follicle apoptosis and other multi-dimensional pathological mechanisms is realized, and meanwhile, through strict raw material quality control, standardized preparation process and whole-process quality monitoring, the quality stability between batches of products and the bioavailability of active components are ensured.

Description

Technical Field

[0001] This application relates to the field of repairing and improving ovarian aging technology, and in particular to a formula and preparation process for repairing and improving ovarian aging. Background Technology

[0002] With increasing awareness of women's health, maintaining ovarian function has become a crucial aspect of delaying aging and ensuring reproductive and overall health. As the core organ regulating female endocrine and reproductive functions, the decline in ovarian function not only triggers perimenopausal symptoms such as menstrual irregularities, hot flashes, and insomnia, but also significantly increases long-term health risks such as osteoporosis, cardiovascular disease, and cognitive impairment. Currently, the need for intervention in ovarian aging is increasingly urgent, especially against the backdrop of intensified lifestyle stress, increased exposure to environmental toxins, and frequent iatrogenic injuries. Premature ovarian failure and declining ovarian reserve are showing a trend towards affecting younger women, necessitating safe, effective, and long-term restorative strategies.

[0003] The technical pathways for repairing and improving ovarian aging mainly encompass hormone replacement therapy, surgical intervention, traditional Chinese medicine conditioning, and dietary supplements. While hormone replacement therapy can quickly relieve symptoms, it carries serious contraindications such as breast cancer and thrombosis, and cannot reverse ovarian tissue damage. Surgical methods are only suitable for specific organic lesions, are highly invasive, and have narrow indications. Although traditional Chinese medicine compound formulas have the advantage of overall conditioning, they are limited by unclear ingredients, slow onset of action, and outdated dosage forms. Existing dietary supplements mostly use single or simple compound ingredients, lacking systematic targeted design for core pathological mechanisms such as oxidative stress, mitochondrial dysfunction, and follicular apoptosis, and are generally not sufficiently clinically validated, resulting in insufficient reliability of efficacy.

[0004] Existing technologies also have significant drawbacks in the preparation processes of related formulations. Conventional physical mixing is insufficient to release plant-derived active ingredients, and high-temperature or organic solvent extraction can easily damage key substances such as heat-sensitive polyphenols and peptides, leading to loss of bioactivity. Furthermore, the lack of precise quantification and standardized control of effective components results in large batch-to-batch quality fluctuations and poor stability, seriously affecting the safety and reproducibility of clinical applications. Therefore, a formulation and preparation process for repairing and improving ovarian aging is needed. Summary of the Invention

[0005] The purpose of this invention is to provide a formula and preparation process for repairing and improving ovarian aging, so as to solve the technical problems mentioned in the background art.

[0006] To achieve the above objectives, the present invention provides the following technical solution: a formula and preparation process for repairing and improving ovarian aging, comprising the following steps: S1: Raw material screening and pretreatment. According to the preset quality standards, the plant raw materials are subjected to sensory inspection, physicochemical index testing and microbial limit testing. Unqualified products are removed, and qualified raw materials are cleaned, dried and pre-crushed. S2: Active ingredient extraction, using dynamic circulating countercurrent extraction technology, with water or a specific concentration of ethanol aqueous solution as the extraction solvent, and multi-stage countercurrent extraction in a temperature range of 40 degrees Celsius to 60 degrees Celsius; S3: Extract purification. The obtained extract is sequentially purified by ceramic membrane microfiltration, hollow fiber ultrafiltration and reverse osmosis membrane separation system to remove macromolecular impurities, colloidal particles and some inorganic salts, and collect active ingredients within the target molecular weight range. S4: Formulation component compounding, the purified active ingredients are mixed with pharmaceutically acceptable excipients in a preset ratio, the excipients include fillers, disintegrants, lubricants and stabilizers, and the powder is mixed using an equal incremental method; S5: Formulation and packaging. The uniformly mixed powder is granulated into granules using dry or wet granulation processes, then compressed into tablets or filled into capsule shells, and finally packaged in aluminum-plastic packaging at a temperature of 15 to 25 degrees Celsius and a relative humidity of 45% to 65%.

[0007] Preferably, the raw material screening in S1 includes high performance liquid chromatography detection of soybean isoflavone raw materials to ensure that the total content of genistein and soybean isoflavone is not less than 40%, and ultraviolet spectrophotometry detection of Rhodiola rosea raw materials to ensure that the content of rhodioloside is not less than 1%.

[0008] Preferably, the dynamic circulating countercurrent extraction device in S2 includes 6-stage series extraction units, each equipped with an independent temperature control system and liquid level monitoring device, the extraction solvent to raw material mass ratio is 8:1 to 12:1, and the residual alcohol content of the residue discharged from the final extraction unit is less than 0.5%.

[0009] Preferably, in S3, the ceramic membrane microfiltration uses a zirconia ceramic membrane with a pore size of 0.1 micrometers; the hollow fiber ultrafiltration uses a polysulfone hollow fiber membrane; and the reverse osmosis membrane separation uses a cellulose acetate composite membrane.

[0010] Preferably, the formulation components in S4 include 15% to 25% soybean isoflavone extract, 8% to 15% Rhodiola rosea extract, 5% to 10% Epimedium extract, 3% to 8% Lycium barbarum polysaccharide, 1% to 3% vitamin E, 0.5% to 1.5% selenium yeast, and the remainder is pharmaceutical excipients. All components are sieved through an 80-mesh sieve.

[0011] Preferably, the excipients in S4 include 40% to 50% microcrystalline cellulose, 3% to 5% crospovidone, 0.5% to 1.5% magnesium stearate, and 0.2% to 0.8% silica.

[0012] Preferably, the active ingredient stabilization treatment is also performed after S3, in which the purified extract is spray-dried under vacuum of -0.08 MPa to -0.1 MPa and temperature of 50°C to 60°C, with a feed rate of 10 to 20 liters per hour and an atomization pressure of 0.2 MPa to 0.4 MPa, to obtain a powder with good flowability and a moisture content of less than 5%.

[0013] Preferably, it also includes intermediate quality testing performed before S5, checking the content uniformity, dissolution and microbial limit of the uniformly mixed particles, ensuring that the content of the main active ingredient in each unit of formulation is in the range of 90% to 110% of the labeled amount, the dissolution rate is not less than 80% within 45 minutes, and the total number of aerobic bacteria is less than 1000 per gram.

[0014] Preferably, the soybean isoflavone extract in the formulation contains three main isoflavones: genistein, soybean flavonoids, and daidzein, wherein genistein accounts for 45% to 55% of the total isoflavones, soybean flavonoids account for 30% to 40%, and daidzein accounts for 10% to 15%; the Rhodiola rosea extract is obtained by using the dried roots and rhizomes of Rhodiola rosea as raw materials, which are extracted by ethanol reflux and then purified by macroporous adsorption resin, wherein the content of rhodioloside is not less than 2%, the content of tyrosol is not less than 0.5%, and the content of total polysaccharides is not less than 15%; the Epimedium extract is prepared by using the dried leaves of Epimedium brevicornu as raw materials, which are prepared by water extraction and alcohol precipitation, wherein the content of epimedin is not less than 5%, and the content of total flavonoids is not less than 30%; the Lycium barbarum polysaccharide is prepared by using the dried fruit of Lycium barbarum from Ningxia as raw materials, which are prepared by hot water extraction, ethanol precipitation, and Sevage deproteinization, wherein the polysaccharide content is not less than 50%, the protein content is less than 2%, and the molecular weight distribution range is 10,000 to 500,000 Daltons.

[0015] Preferably, the preparation process also includes an online quality monitoring system, in which near-infrared spectral probes are set at key process steps to monitor the content of active ingredients and moisture content in real time, and the monitoring data is fed back to the central control system to automatically adjust the process parameters; the particle size distribution of each component in the formula is controlled to be less than 75 micrometers with a D90, and the relative standard deviation of the content of active ingredients between different batches is less than 3%; the product is subjected to accelerated testing at 40 degrees Celsius and 75% relative humidity for 6 months, and the content of the main active ingredients remains above 95% of the initial content.

[0016] Compared with the prior art, the beneficial effects of the present invention are: By scientifically combining multiple natural active ingredients with clear pharmacological effects and employing advanced dynamic circulating countercurrent extraction technology and multi-stage membrane separation purification process, a systematic intervention on multidimensional pathological mechanisms such as ovarian aging-related oxidative stress, mitochondrial dysfunction, and follicular apoptosis has been achieved. At the same time, through strict raw material quality control, standardized preparation process, and full-process quality monitoring, the batch-to-batch quality stability and bioavailability of active ingredients have been ensured. Attached Figure Description

[0017] Figure 1 This is a schematic diagram of the steps of the present invention. Detailed Implementation

[0018] 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.

[0019] refer to Figure 1 A formula and preparation process for repairing and improving ovarian aging, comprising the following steps: S1: Raw material screening and pretreatment. According to the preset quality standards, the plant raw materials are subjected to sensory inspection, physicochemical index testing and microbial limit testing. Unqualified products are removed, and qualified raw materials are cleaned, dried and pre-crushed to control the moisture content of the raw materials between 8% and 12%. Specifically, raw material screening includes high-performance liquid chromatography (HPLC) analysis of soybean isoflavone raw materials to ensure that the total content of genistein and soybean isoflavone is not less than 40%, and ultraviolet spectrophotometry analysis of Rhodiola rosea raw materials to ensure that the content of rhodioloside is not less than 1%. All raw materials comply with the relevant regulations of the Chinese Pharmacopoeia regarding heavy metal content. Sensory inspection of raw materials covers appearance indicators such as color, odor, and impurity content. Physicochemical indicators include routine items such as moisture, ash, and extractives. Microbiological limit testing is conducted according to Chinese Pharmacopoeia General Chapters 1105 and 1106, testing for total aerobic bacteria count, total mold and yeast count, and control bacteria. The washing process involves three rinses with running drinking water to remove surface mud and soluble impurities. Drying is performed in a hot air circulating oven at 50-60 degrees Celsius until the moisture content stabilizes between 8% and 12%. Preliminary pulverization uses a universal pulverizer, and the pulverized material is passed through a 20-mesh sieve to ensure uniform particle size, facilitating efficient mass transfer in subsequent extraction processes. The goal of this step is to address the problems of large fluctuations in raw material quality, unclear content of effective components, and serious interference from impurities in existing technologies, so as to provide standardized and high-purity starting materials for subsequent processes.

[0020] S2: Active ingredient extraction, using dynamic circulating countercurrent extraction technology, with water or a specific concentration of ethanol aqueous solution as the extraction solvent, multi-stage countercurrent extraction is carried out in the temperature range of 40 degrees Celsius to 60 degrees Celsius, the extraction pressure is maintained at 0.1 MPa to 0.3 MPa, the single extraction time is 90 minutes to 150 minutes, and the circulation flow rate is 100 liters to 200 liters per hour; Specifically, the dynamic circulating countercurrent extraction equipment includes 6 extraction units in series, each equipped with an independent temperature control system and liquid level monitoring device. The extraction solvent to raw material mass ratio is 8:1 to 12:1, and the residual alcohol content of the residue discharged from the final extraction unit is less than 0.5%. The dynamic circulating countercurrent extraction system consists of six extraction tanks connected in series. Fresh solvent is added from the sixth stage, contacting the extracted residue. The extract flows sequentially to the next stage, with the final high-concentration extract exiting from the first stage. Each extraction tank is equipped with a jacketed heating system, which uses a PID controller to precisely maintain the internal temperature within the range of 40°C to 60°C, preventing the degradation of heat-sensitive components such as polyphenols and saponins. A level sensor monitors the liquid level in real time to ensure a constant material-to-solvent ratio. A circulating pump drives the extract to circulate between stages at a flow rate of 100 to 200 liters per hour, enhancing solid-liquid phase contact. For components such as soy isoflavones and icariin, a 60% to 70% (v / v) ethanol aqueous solution is used as the solvent; for wolfberry polysaccharides, pure water is used. The entire extraction process is carried out in a closed system, with the pressure controlled at 0.1 to 0.3 MPa by a back pressure valve, ensuring both a rise in the solvent boiling point to maintain the liquid state and preventing the loss of volatile components. The final stage of the extract, analyzed by online gas chromatography, showed a residual alcohol content of less than 0.5%, ensuring high solvent recovery and environmental friendliness. This step aims to address the problems of low efficiency, high energy consumption, and severe component damage associated with traditional decoction or reflux extraction, achieving a green extraction process with high yield, high purity, and low solvent residue.

[0021] S3: Extract purification. The obtained extract is sequentially purified by ceramic membrane microfiltration, hollow fiber ultrafiltration and reverse osmosis membrane separation system to remove macromolecular impurities, colloidal particles and some inorganic salts, and collect active ingredients within the target molecular weight range. Specifically, ceramic membrane microfiltration uses zirconia ceramic membranes with a pore size of 0.1 micrometers and an operating pressure of 0.2 MPa to 0.4 MPa; hollow fiber ultrafiltration uses polysulfone hollow fiber membranes with a molecular weight cutoff of 10,000 Daltons and a transmembrane pressure difference of 0.1 MPa to 0.2 MPa; reverse osmosis membrane separation uses cellulose acetate composite membranes with a desalination rate greater than 98% and an operating pressure of 1.5 MPa to 2.5 MPa. The extract is first pretreated (e.g., pH adjusted to neutral, preheated to 40°C) before entering the ceramic membrane microfiltration system. The zirconia ceramic membrane, with its high mechanical strength, acid and alkali resistance, and high-temperature resistance, effectively retains suspended particles, starch, protein aggregates, and other large molecular impurities under an operating pressure of 0.2 MPa to 0.4 MPa, resulting in a clear and transparent permeate. The microfiltration permeate then enters the hollow fiber ultrafiltration system. The polysulfone hollow fiber membrane, under a transmembrane pressure difference of 0.1 MPa to 0.2 MPa, retains polysaccharides, tannins, and some pigments with molecular weights greater than 10,000 Daltons, while target active small molecules such as isoflavone glycosides, rhodioloside, and icariin permeate through the membrane pores to the next stage. The ultrafiltration permeate then enters the reverse osmosis system. The cellulose acetate composite membrane, under a high pressure of 1.5 MPa to 2.5 MPa, selectively allows water molecules to pass through while retaining inorganic salt ions and small-molecule organic acids, achieving a desalination rate greater than 98%, significantly reducing product ash content and improving purity.

[0022] All three membrane separation processes employ cross-flow filtration to reduce membrane fouling and are equipped with an automatic backwashing program to ensure long-term stable operation of the system.

[0023] It also includes an active ingredient stabilization treatment after S3, in which the purified extract is spray-dried under vacuum of -0.08 MPa to -0.1 MPa and temperature of 50°C to 60°C, with a feed rate of 10 to 20 liters per hour and an atomization pressure of 0.2 to 0.4 MPa, to obtain a free-flowing powder with a moisture content of less than 5%. The spray drying tower adopts a co-flow design. The purified liquid is fed into the atomizer at the top of the tower by a peristaltic pump at a rate of 10 to 20 liters per hour, and atomized into micron-sized droplets under a compressed air pressure of 0.2 MPa to 0.4 MPa. Hot air inside the tower is heated to 160 to 180 degrees Celsius by an electric heater and comes into contact with the droplets in co-flow, causing the moisture to evaporate instantly. A vacuum of -0.08 MPa to -0.1 MPa is maintained inside the tower to lower the boiling point and protect heat-sensitive components. The dried powder is collected by a cyclone separator. Its moisture content, determined by Karl Fischer method, is less than 5%, its bulk density is 0.4 g / mL to 0.6 g / mL, its angle of repose is less than 40 degrees, and it has good flowability, facilitating subsequent compounding.

[0024] S4: Formulation component compounding: The purified active ingredients are mixed with pharmaceutically acceptable excipients in a preset ratio. The excipients include fillers, disintegrants, lubricants, and stabilizers. The powders are mixed using an equal-incremental method to ensure that the coefficient of variation of the mixing uniformity is less than 5%. Specifically, the formula components include 15% to 25% soybean isoflavone extract, 8% to 15% Rhodiola rosea extract, 5% to 10% Epimedium extract, 3% to 8% Lycium barbarum polysaccharide, 1% to 3% vitamin E, 0.5% to 1.5% selenium yeast, and the remainder is pharmaceutical excipients. All components are sieved through an 80-mesh sieve. Pharmaceutically acceptable excipients include 40% to 50% microcrystalline cellulose, 3% to 5% crospovidone, 0.5% to 1.5% magnesium stearate and 0.2% to 0.8% silica, and all excipients comply with the pharmaceutical standards of the Chinese Pharmacopoeia. All active ingredient powders and excipients were sieved through an 80-mesh vibrating sieve before mixing to ensure uniform particle size. The mixing process was carried out in a three-dimensional motion mixer. First, soybean isoflavone extract was mixed with an equal amount of microcrystalline cellulose for 5 minutes. Then, an equal amount of the mixture was added and mixed with the remaining microcrystalline cellulose for 10 minutes. Subsequently, Rhodiola rosea extract, Epimedium extract, Lycium barbarum polysaccharide, vitamin E, and selenium yeast were added sequentially, mixing for 5 minutes after each addition. Finally, crospovidone and silica were added and mixed for 10 minutes. Magnesium stearate was added in the last 2 minutes. After mixing, 10 samples were taken, and the soybean isoflavone content was determined using high-performance liquid chromatography (HPLC). The coefficient of variation for mixing uniformity was calculated, ensuring it was less than 5%.

[0025] The formula contains three main isoflavones: genistein, daidzein, and genistein. Genistein accounts for 45% to 55% of the total isoflavones, daidzein for 30% to 40%, and genistein for 10% to 15%. The Rhodiola rosea extract is obtained from the dried roots and rhizomes of Rhodiola rosea, extracted by ethanol reflux followed by purification using macroporous adsorption resin. The extract contains at least 2% rhodioloside, at least 0.5% tyrosol, and at least 15% total polysaccharides. The Epimedium extract is prepared from the dried leaves of Epimedium brevicornu, using a water extraction and alcohol precipitation method. The extract contains at least 5% epimedin and at least 30% total flavonoids. The Lycium barbarum polysaccharide is prepared from the dried fruit of Lycium barbarum from Ningxia, using hot water extraction, ethanol precipitation, and Sevage deproteinization. The polysaccharide content is at least 50%, the protein content is less than 2%, and the molecular weight ranges from 10,000 to 500,000 Daltons.

[0026] S5: Formulation and packaging: The uniformly mixed powder is granulated into granules using dry or wet granulation processes, then compressed into tablets or filled into capsule shells, and finally packaged in aluminum-plastic packaging at a temperature of 15 to 25 degrees Celsius and a relative humidity of 45% to 65%. Specifically, in step 5, the dry granulation uses a roller press granulator with a roller pressure of 30 kN to 50 kN and a roller gap of 1.0 mm to 2.0 mm, resulting in granules with a bulk density of 0.6 g / mL to 0.8 g / mL and an angle of repose of less than 35 degrees. In step 5, the wet granulation uses a high-speed shear granulator with a binder of 5% to 10% povidone K30 ethanol solution, the binder being added at 15% to 25% of the total material weight. The granulation blade speed is 200 rpm to 400 rpm, and the granulation time is controlled between 3 and 8 minutes. Dry granulation is suitable for moisture-sensitive formulations. The mixed powder is fed into a roller press via a forced feeder and pressed into thin sheets under a pressure of 30 to 50 kN, then crushed into granules by a granulator. Wet granulation is suitable for applications requiring improved flowability. The binder solution is metered into the high-speed rotating material via a peristaltic pump, and granules are formed by shearing under granulation blades at 200 to 400 rpm. The wet granules are then dried in a fluidized bed until the moisture content is below 3%, and then granulated. The resulting granules are compressed into tablets (0.5 g per tablet) by a rotary tablet press or filled into size 0 capsule shells by an automatic capsule filling machine. The finished product is packaged in a cleanroom at 15 to 25 degrees Celsius and a relative humidity of 45% to 65% using an aluminum-plastic blister packaging machine, with 10 capsules per blister pack, heat-sealed at 180 degrees Celsius, ensuring good sealing.

[0027] This also includes intermediate quality testing prior to step 5, which involves checking the content uniformity, dissolution rate, and microbial limits of the uniformly mixed granules to ensure that the content of the main active ingredient in each unit of formulation is within 90% to 110% of the labeled amount, the dissolution rate is not less than 80% within 45 minutes, and the total aerobic bacteria count is less than 1000 per gram. The content uniformity test is conducted according to Chinese Pharmacopoeia General Chapter 0942. The dissolution test uses a paddle method at 50 rpm in 900 ml of pH 6.8 phosphate buffer, with sampling and testing every 45 minutes. The microbial limit test is conducted according to General Chapters 1105 and 1106. Only intermediates that pass all tests can proceed to the packaging process.

[0028] In specific implementation: the preparation process also includes an online quality monitoring system, in which near-infrared spectroscopy probes are set at key process steps to monitor the content of active ingredients and moisture content in real time, and the monitoring data is fed back to the central control system to automatically adjust the process parameters; the particle size distribution of each component in the formula is controlled to be less than 75 micrometers with D90, and the relative standard deviation of the content of active ingredients between different batches is less than 3%; the product is subjected to accelerated testing at 40 degrees Celsius and 75% relative humidity for 6 months, and the content of the main active ingredients remains above 95% of the initial content; Near-infrared probes are installed at the extraction tank outlet, the permeate pipeline of the membrane separation system, the feed inlet of the spray drying tower, and the discharge outlet of the mixer. Spectral data is collected every 30 seconds. Key indicators are predicted in real time through a pre-established PLS regression model, and deviation signals are sent to the DCS system to automatically adjust parameters such as temperature, flow rate, and pressure to achieve closed-loop control.

[0029] Although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art can still modify the technical solutions described in the foregoing embodiments or make equivalent substitutions for some of the technical features. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. A formula and preparation process for repairing and improving ovarian aging, characterized in that: Including the following step: S1: Raw material screening and pretreatment. According to the preset quality standards, the plant raw materials are subjected to sensory inspection, physicochemical index testing and microbial limit testing. Unqualified products are removed, and qualified raw materials are cleaned, dried and pre-crushed. S2: Active ingredient extraction, using dynamic circulating countercurrent extraction technology, with water or a specific concentration of ethanol aqueous solution as the extraction solvent, and multi-stage countercurrent extraction in a temperature range of 40 degrees Celsius to 60 degrees Celsius; S3: Extract purification. The obtained extract is sequentially purified by ceramic membrane microfiltration, hollow fiber ultrafiltration and reverse osmosis membrane separation system to remove macromolecular impurities, colloidal particles and some inorganic salts, and collect active ingredients within the target molecular weight range. S4: Formulation component compounding, the purified active ingredients are mixed with pharmaceutically acceptable excipients in a preset ratio, the excipients include fillers, disintegrants, lubricants and stabilizers, and the powder is mixed using an equal incremental method; S5: Formulation and packaging. The uniformly mixed powder is granulated into granules using dry or wet granulation processes, then compressed into tablets or filled into capsule shells, and finally packaged in aluminum-plastic packaging at a temperature of 15 to 25 degrees Celsius and a relative humidity of 45% to 65%.

2. The formula and preparation process for repairing and improving ovarian aging according to claim 1, characterized in that: The raw material screening in S1 includes high performance liquid chromatography detection of soybean isoflavone raw materials to ensure that the total content of genistein and soybean isoflavone is not less than 40%, and ultraviolet spectrophotometry detection of Rhodiola rosea raw materials to ensure that the content of rhodioloside is not less than 1%.

3. The formula and preparation process for repairing and improving ovarian aging according to claim 1, characterized in that: The dynamic circulating countercurrent extraction equipment in S2 includes 6-stage series extraction units. Each stage is equipped with an independent temperature control system and a liquid level monitoring device. The mass ratio of extraction solvent to raw material is 8:1 to 12:

1. The residual alcohol content of the residue discharged from the final extraction unit is less than 0.5%.

4. The formula and preparation process for repairing and improving ovarian aging according to claim 1, characterized in that: The ceramic membrane microfiltration in S3 uses a zirconium oxide ceramic membrane with a pore size of 0.1 micrometers; Hollow fiber ultrafiltration uses polysulfone hollow fiber membranes; reverse osmosis membrane separation uses cellulose acetate composite membranes.

5. The formula and preparation process for repairing and improving ovarian aging according to claim 1, characterized in that: The formulation components of S4 include 15% to 25% soybean isoflavone extract, 8% to 15% Rhodiola rosea extract, 5% to 10% Epimedium extract, 3% to 8% Lycium barbarum polysaccharide, 1% to 3% vitamin E, 0.5% to 1.5% selenium yeast, and the remainder is pharmaceutical excipients. All components are sieved through an 80-mesh sieve.

6. The formula and preparation process for repairing and improving ovarian aging according to claim 1, characterized in that: The excipients in S4 include 40% to 50% microcrystalline cellulose, 3% to 5% crospovidone, 0.5% to 1.5% magnesium stearate, and 0.2% to 0.8% silica.

7. The formula and preparation process for repairing and improving ovarian aging according to claim 1, characterized in that: It also includes an active ingredient stabilization treatment after S3, in which the purified extract is spray-dried under vacuum of -0.08 MPa to -0.1 MPa and temperature of 50°C to 60°C, with a feed rate of 10 to 20 liters per hour and an atomization pressure of 0.2 MPa to 0.4 MPa, to obtain a powder with good flowability and a moisture content of less than 5%.

8. The formula and preparation process for repairing and improving ovarian aging according to claim 1, characterized in that: It also includes intermediate quality testing conducted before S5, content uniformity testing, dissolution testing, and microbial limit testing of uniformly mixed particles, ensuring that the content of the main active ingredient in each unit of formulation is in the range of 90% to 110% of the labeled amount, the dissolution rate is not less than 80% within 45 minutes, and the total number of aerobic bacteria is less than 1000 per gram.

9. The formula and preparation process for repairing and improving ovarian aging according to claim 5, characterized in that: The formula contains three main isoflavones: genistein, daidzein, and genistein. Genistein accounts for 45% to 55% of the total isoflavones, daidzein accounts for 30% to 40%, and genistein accounts for 10% to 15%. The Rhodiola rosea extract is obtained from the dried roots and rhizomes of Rhodiola rosea, extracted by ethanol reflux and purified by macroporous adsorption resin. The extract contains at least 2% rhodioloside, at least 0.5% tyrosol, and at least 15% total polysaccharides. The Epimedium extract is prepared from the dried leaves of Epimedium brevicornu, using a water extraction and alcohol precipitation method. The extract contains at least 5% epimedin and at least 30% total flavonoids. The Lycium barbarum polysaccharide is prepared from the dried fruit of Lycium barbarum from Ningxia, using hot water extraction, ethanol precipitation, and Sevage deproteinization. The polysaccharide content is at least 50%, the protein content is less than 2%, and the molecular weight range is 10,000 to 500,000 Daltons.

10. The formula and preparation process for repairing and improving ovarian aging according to claim 1, characterized in that: The preparation process also includes an online quality monitoring system, in which near-infrared spectral probes are set at key process steps to monitor the content of active ingredients and moisture content in real time, and the monitoring data is fed back to the central control system to automatically adjust the process parameters. The particle size distribution of each component in the formula is controlled to be less than 75 micrometers with a D90, and the relative standard deviation of the content of active ingredients between different batches is less than 3%. The product is subjected to accelerated testing at 40 degrees Celsius and 75% relative humidity for 6 months, and the content of the main active ingredients remains above 95% of the initial content.

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