Preparation and detection method of twenty-five-ingredient emblic leafflower fruit pill for preventing and treating high altitude polycythemia
Through research on the medicinal material source of Twenty-Five Flavor Phyllanthus emblica pills, optimization of NIR online control and detection methods, the problems of unclear mechanism and unstable quality of Twenty-Five Flavor Phyllanthus emblica pills in the treatment of high-altitude polycythemia have been solved, realizing the stability of drug quality and the accuracy of detection, and improving the reliability of clinical drug use.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- TIBET JINLUN TIBETAN MEDICINE DEV CO LTD
- Filing Date
- 2026-02-27
- Publication Date
- 2026-05-12
AI Technical Summary
The mechanism of action of the Twenty-Five Flavor Phyllanthus Pill in treating high-altitude polycythemia is unclear in the existing technology, which limits the precise clinical use of the drug. Furthermore, the lack of effective quality control methods in the production process leads to unstable product quality.
By establishing a dual-standard spectral library of control medicinal materials and counterfeit products, online NIR control of the pulverization-mixing-sterilization process, near-infrared principal component analysis, and data fusion, rapid screening and simultaneous quantification of key drug components can be achieved. Combined with detection methods using a simulated high-altitude chamber model, the consistency of drug quality and efficacy can be ensured.
This has achieved consistency in the quality and efficacy of the Twenty-Five Flavor Phyllanthus Pill, reduced batch fluctuations, improved the sensitivity and accuracy of drug testing, shortened the quality control cycle, and reduced recall costs.
Smart Images
Figure CN122016700A_ABST
Abstract
Description
Technical Field
[0001] This invention relates to the field of traditional Chinese medicine compound preparation technology, and in particular to a method for preparing and testing a 25-ingredient Phyllanthus emblica pill for the prevention and treatment of high altitude polycythemia. Background Technology
[0002] With the rapid development of the traditional Chinese medicine industry, the safety and quality stability of traditional Chinese medicine products have become key factors affecting the development of traditional Chinese medicine. Therefore, under the background of the construction of the national standardization system, the whole-process quality control of the traditional Chinese medicine industry has received widespread attention. Meanwhile, with the National Medical Products Administration's "Requirements for Registration Classification and Application Materials of Traditional Chinese Medicine," which stipulates that traditional Chinese medicines with added functions and indications are considered improved new drugs, new avenues for pharmaceutical companies' development have been broadened. In recent years, with the widespread attention given to Tibetan medicine, the Twenty-Five Flavor Phyllanthus Pill has been increasingly used in clinical practice. The prescription is a compound preparation made from twenty-six medicinal materials, including Phyllanthus emblica, Baxiaga, artificial bezoar, and Ganqingqinglan. Clinically, it is used for symptoms such as chest and back fullness, liver and gallbladder pain, hoarseness, red eyes, cyanosis of the lips, and menstrual disorders caused by hypertension and polycythemia. Currently, the pharmacological effect of the Twenty-Five Flavor Phyllanthus Pill is mainly reflected in its ability to significantly improve hypertension. Hypertension has clinical symptoms similar to those of "black vein disease" in Mongolian medicine. At the same time, clinical studies have found that the Twenty-Five Flavor Phyllanthus Pill can be used as a drug to treat high-altitude polycythemia. However, there are currently no studies reporting the therapeutic mechanism of the Twenty-Five Flavor Phyllanthus Pill for high-altitude polycythemia and the dose-effect relationship in clinical application. Therefore, its precise clinical use is limited. This project explores the relevant mechanisms to provide a theoretical basis for future treatment.
[0003] Based on the "quality by design" principle, in the process of adding new indications to research, we will review the parameters of the traditional Chinese medicine production process from the source of research and development. This is because variations in raw material quality, fluctuations in process parameters, and the lack of strict quality control standards and effective monitoring methods can all lead to differences in product quality between different batches. To ensure the stability and uniformity of the final product quality, it is necessary to establish reasonable quality standards for key control points in the production process and research effective testing methods to achieve control over the entire production process. As the manufacturer of this medicine, the construction of a comprehensive quality control system is particularly important. Tibetan medicine production has made significant progress in recent years, with most preparations adding internal control testing of chemical components. With the standardization of drug re-registration in the Tibet Autonomous Region and the increased regulatory efforts on traditional Chinese medicine, the re-registration of Tibetan medicine is continuing. The production of the same Tibetan medicine by different manufacturers is becoming more consistent. This will break the previous situation where the prescription composition, source of Tibetan medicinal materials, and processing techniques varied, making it difficult to form a unified standard for quality control. Therefore, it is of paramount importance for pharmaceutical manufacturers to conduct systematic research on single-variety products, starting from the source of medicinal materials, including the source and testing of medicinal materials, processing techniques and quality control, preparation techniques and quality control of semi-finished and finished products, as well as related heavy metals and bacteria. Summary of the Invention
[0004] To address the deficiencies in existing technologies, this invention provides a method for preparing a 25-ingredient amla pill for the prevention and treatment of high-altitude polycythemia, including S1, studying the source of medicinal materials and establishing a dual-label spectral library method for control medicinal materials and counterfeit products; S2. Parameterization and verification of the processing technology of medicinal slices; S3. Online NIR control of the pulverizing-mixing-sterilization process; S4. Use near-infrared principal component analysis to quickly screen finished or semi-finished products and simultaneously quantify key drug components. S5, Data Fusion and Batch Release.
[0005] Furthermore, the establishment of the research on the source of medicinal materials includes multiple source medicinal materials such as Phyllanthus emblica, Meconopsis thunbergii, and Trichosanthes kirilowii seeds. The unique source is fixed by dual identification through HPLC-DAD / ITS2 barcode and combined with the frequency of clinical use in Tibetan medicine. If a second source needs to be introduced, it is fixed at a weight ratio of 7:3 and traced in the production batch record. For mineral medicines, specify the type, group, ore name or rock name of the mineral, as well as its main components.
[0006] Furthermore, the method for establishing a dual-standard chromatographic library of reference medicinal materials and counterfeit products includes, for easily confused medicinal materials, firstly using thin-layer chromatography to screen out the chemical and chromatographic dual indicators that have the greatest differences and are stable, wherein the chemical indicator is the peak area ratio of two characteristic components, and the chromatographic indicator is a specific spot, requiring a fixed Rf value and distinct colorimetric characteristics; The peak ratio R was determined for a large number of representative samples, and the critical value R0 was determined by ROC curve or 95% confidence interval. For the specific spot M, confirm its detection limit. A positive result is defined as clearly visible and with an Rf value consistent with the control, while a negative result is defined as no corresponding spot or an intensity less than the detection limit. If R is less than or equal to R0 and M is negative, it is classified as a chemical indicator; if R is greater than R0 or M is positive, it is classified as a chromatographic indicator. Cross-validation, blind sample testing, and verification by different laboratories were employed to ensure reproducibility; the stability of R0 and M spots was periodically verified using control medicinal materials.
[0007] Furthermore, the online NIR control of the pulverization-mixing-sterilization process includes a particle size model, a mixing uniformity model, and a moisture and sterilization coupling model. The particle size model uses discriminant analysis to lock the 10–80 mesh range. The uniformity model uses a ternary system as a tracer and a moving window F test to capture the mixing endpoint in real time. The moisture model uses the 1940 nm absorption peak as a gate and links it to the sterilization process.
[0008] Furthermore, all particle size models, mixing uniformity models, and moisture and sterilization coupling models share the same hardware configuration: fiber optic probes 2 mm from the sample, integration 10 ms, and full-band acquisition of 1000–2500 nm; spectral thresholds are set for each key quality attribute (CQA). Granularity prediction error RSD is less than 5%; If the uniformity similarity is greater than or equal to 0.985, stop the propeller. Only products with a moisture content of 8% or less are allowed to undergo ethylene oxide sterilization, and the residual moisture content after sterilization is 0.1 ppm or less.
[0009] Furthermore, the method for rapid screening of finished or semi-finished products using near-infrared principal component analysis is as follows: 30 pills are randomly selected from each batch, crushed, and placed in a rotating sample cup, and the near-infrared full spectrum is acquired with one click; a 99% confidence control limit is set using the Hotelling T² statistic, and any abnormal point deviating from the confidence ellipse immediately triggers an audible and visual alarm.
[0010] Furthermore, the simultaneous quantification of key drug components includes, A1 efficacy anchor gallic acid: conventional HPLC-UV (280nm, C18 gradient elution) was used, with a lower limit of ≥12mg / pill to ensure effective dosage; A2 safety anchor aristolochic acid: Highly sensitive UPLC-MS / MS (MRM 359→296) was used, with an upper limit set at ≤0.10µg / pill to ensure that the toxicity threshold is far below regulatory requirements; A3 uses TLC-bioautoradiography as a secondary verification method to construct a "chemical-activity" dual spectrum: eight characteristic medicinal materials, including Phyllanthus emblica, Meconopsis, Dalbergia odorifera, Lithospermum erythrorhizon, Aucklandia lappa, Aristolochia debilis, Trichosanthes kirilowii seeds, and Carthamus tinctorius, were selected to prepare a mixed control medicinal material accompanying plate; after development under the same chromatographic conditions, the spots were first located with visible / ultraviolet light, and then the antioxidant active spots were displayed by DPPH bioautoradiography.
[0011] Furthermore, the data fusion and batch release includes inputting all data from S1 to S4 into the MES system and generating a QR code; A multivariate statistical process control model was established. The product could only be released when particle size, moisture, uniformity, gallic acid, and aristolochic acid were all within the Hotelling T2 95% control limit and the microorganisms met the control requirements for Tibetan medicine preparations.
[0012] A method for detecting the 25-Flavor Phyllanthus emblica pill used to prevent and treat high-altitude polycythemia, comprising: Step 1: Establish a large and small mouse HAPC model in a simulated high-altitude chamber; Step 2: Set up high-dose and low-dose WY pill groups, and use 0.2 mL of tail vein micro-volume blood to perform microRNA detection of erythrocytes, hemoglobin, hematocrit, lactate, erythropoietin, hypoxia-inducible factor-1α, and HIF-1α directly induced by microfluidic chip in one step; Step 3: Construct an "anti-HAPC index" using standardized scores of six indicators, and establish an NIR-PLSR model to achieve 15-second non-destructive prediction; Step 4: Calculate the ED50 of high and low doses using the Emax model. A significant dose-response relationship is determined when the ratio of high to low dose ED50 is ≥3. Step 5: If hypoxia-inducible factor-1α↓≥30%, erythropoietin↓≥25%, miR-210↑≥40%, SOD↑≥20%, and MDA↓≥20%, then WY pills are automatically determined to exert their anti-HAPC effect through the "microRNA axis directly induced by hypoxia-inducible factor-1α-erythropoietin-HIF-1α".
[0013] Preferably, the NIR spectral acquisition conditions are: 1000-2500 nm, resolution 2 cm⁻¹, fiber optic probe distance from sample 2 mm, integration time 10 ms. The micro-blood chip is injection molded from polymethyl methacrylate (PMMA) in one piece and incorporates an impedance microelectrode, lactase membrane, ELISA microcell, and qRT-PCR reaction chamber. The qRT-PCR is a technique that adds a fluorescent group to traditional PCR and monitors the amplification product in real time through fluorescence signal to achieve precise quantification of the starting template.
[0014] Beneficial effects: Compared with the prior art, the present invention provides a method for preparing and detecting a 25-ingredient amla pill for the prevention and treatment of high-altitude polycythemia, which has the following beneficial effects: The beneficial effects of this invention are reflected in: 1. In this invention, each medicinal material is fixed with a four-level code: species, part, variety, and place of origin. For those with multiple sources, a proportion range is given and written into the quality standard. This eliminates batch fluctuations caused by different species with the same name or different substances of the same species from the source, reducing the dispersion of the finished product's efficacy. A triple comparison is made using control medicinal materials, control extracts, and standard chromatograms, supplemented by parallel comparison with counterfeit products. The specific peak recognition rate of TLC / HPLC / UPLC-MS fingerprint chromatograms is greater than or equal to 98%, improving the sensitivity of detecting adulterants. All data from source to processing to finished product are connected to the enterprise's quality traceability platform and integrated with NIR online monitoring to achieve real-time feedback from "source to intermediate to final product". Annual review analysis can detect trend deviations in advance, shorten the change control cycle, and reduce quality risks and recall costs. Attached Figure Description
[0015] To more clearly illustrate the specific embodiments of the present invention or the technical solutions in the prior art, the accompanying drawings used in the description of the specific embodiments or the prior art will be briefly introduced below. In all the drawings, similar elements or parts are generally identified by similar reference numerals. In the drawings, the elements or parts are not necessarily drawn to scale.
[0016] Figure 1 This is a schematic flowchart of the preparation method of the Twenty-Five Flavor Phyllanthus Pill for the prevention and treatment of high altitude polycythemia in Example 1. Detailed Implementation
[0017] 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.
[0018] like Figure 1 As shown, a method for preparing a 25-ingredient amla pill for the prevention and treatment of high-altitude polycythemia includes the following steps: S1. Study the source of medicinal materials and establish a dual-standard spectral library method for control medicinal materials and counterfeit products; S2. Parameterization and verification of the processing technology of medicinal slices; S3. Online NIR control of the pulverizing-mixing-sterilization process; S4. Use near-infrared principal component analysis to quickly screen finished or semi-finished products and simultaneously quantify key drug components. S5, Data Fusion and Batch Release.
[0019] In this embodiment, the establishment of the research on the source of medicinal materials includes multiple source medicinal materials such as Phyllanthus emblica, Meconopsis thunbergii, and Trichosanthes kirilowii seeds. The unique source is fixed by dual identification through HPLC-DAD / ITS2 barcode and combined with the frequency of clinical use in Tibetan medicine. If a second source needs to be introduced, it is fixed at a weight ratio of 7:3 and traced in the production batch record. For mineral medicines, specify the type, group, ore name or rock name of the mineral, as well as its main components.
[0020] For example, the mineral drug "iron powder" (mainly containing Fe3O4 ≥ 85%) was identified by dual-targeting of class-group components using X-ray diffraction (XRD) and inductively coupled plasma mass spectrometry (ICP-MS).
[0021] In this embodiment, the method for establishing a dual-standard spectral library of reference medicinal materials and counterfeit products includes, for easily confused medicinal materials, firstly using thin-layer chromatography to screen out the chemical and chromatographic dual indicators that have the greatest differences and are stable, wherein the chemical indicator is the peak area ratio of two characteristic components, and the chromatographic indicator is a specific spot, requiring a fixed Rf value and distinct colorimetric characteristics; The peak ratio R was determined for a large number of representative samples, and the critical value R0 was determined by ROC curve or 95% confidence interval. For the specific spot M, confirm its detection limit. A positive result is defined as clearly visible and with an Rf value consistent with the control, while a negative result is defined as no corresponding spot or an intensity less than the detection limit. If R is less than or equal to R0 and M is negative, it is classified as a chemical indicator; if R is greater than R0 or M is positive, it is classified as a chromatographic indicator. Cross-validation, blind sample testing, and verification by different laboratories were employed to ensure reproducibility; the stability of R0 and M spots was periodically verified using control medicinal materials.
[0022] In this embodiment, the NIR online control of the pulverization-mixing-sterilization process includes a particle size model, a mixing uniformity model, and a moisture and sterilization coupling model. The particle size model uses discriminant analysis to lock the 10–80 mesh range. The uniformity model uses a ternary system as a tracer and a moving window F test to capture the mixing endpoint in real time. The moisture model uses the 1940 nm absorption peak as a gate and links it to the sterilization process.
[0023] In this embodiment, all particle size models, mixing uniformity models, and moisture and sterilization coupling models share the same hardware configuration: fiber optic probe distance of 2 mm, integration of 10 ms, and full-band acquisition of 1000–2500 nm. Spectral thresholds are set for each key quality attribute (CQA). Granularity prediction error RSD is less than 5%; If the uniformity similarity is greater than or equal to 0.985, stop the propeller. Only products with a moisture content of 8% or less are allowed to undergo ethylene oxide sterilization, and the residual moisture content after sterilization is 0.1 ppm or less.
[0024] In this embodiment, the method for rapid screening of finished or semi-finished products using near-infrared principal component analysis is as follows: 30 pills are randomly selected from each batch, crushed, and placed in a rotating sample cup, and the near-infrared full spectrum is acquired with one click; a 99% confidence control limit is set using the Hotelling T² statistic, and any abnormal point deviating from the confidence ellipse will immediately trigger an audible and visual alarm.
[0025] Specifically, the quality of finished and semi-finished products is ensured by randomly selecting samples for testing.
[0026] In this embodiment, the simultaneous quantification of key drug components includes, A1 efficacy anchor gallic acid: conventional HPLC-UV (280nm, C18 gradient elution) was used, with a lower limit of ≥12mg / pill to ensure effective dosage; A2 safety anchor aristolochic acid: Highly sensitive UPLC-MS / MS (MRM 359→296) was used, with an upper limit set at ≤0.10µg / pill to ensure that the toxicity threshold is far below regulatory requirements; A3 uses TLC-bioautoradiography as a secondary verification method to construct a "chemical-activity" dual spectrum: eight characteristic medicinal materials, including Phyllanthus emblica, Meconopsis, Dalbergia odorifera, Lithospermum erythrorhizon, Aucklandia lappa, Aristolochia debilis, Trichosanthes kirilowii seeds, and Carthamus tinctorius, were selected to prepare a mixed control medicinal material accompanying plate; after development under the same chromatographic conditions, the spots were first located with visible / ultraviolet light, and then the antioxidant active spots were displayed by DPPH bioautoradiography.
[0027] Specifically, the spectral layer provides an alarm result within 30 seconds, the chromatographic layer provides an "efficacy-safety" value within 15 minutes, and the thin-layer chromatography provides visual evidence of "authenticity and activity of medicinal materials" within 20 minutes. When these three are linked together, they not only cover 100% of batches but also identify key risks, resulting in "60% reduction in inspection time and a 3-fold increase in inspection throughput." Ultimately, this upgrades the "semi-finished product-finished product" quality evaluation into an auditable, traceable, and predictable digital release system.
[0028] In this embodiment, the data fusion and batch release includes inputting all data from S1 to S4 into the MES system and generating a QR code; A multivariate statistical process control model was established. The product could only be released when particle size, moisture, uniformity, gallic acid, and aristolochic acid were all within the Hotelling T2 95% control limit and the microorganisms met the control requirements for Tibetan medicine preparations.
[0029] A method for detecting the 25-Flavor Phyllanthus emblica pill used to prevent and treat high-altitude polycythemia, comprising: Step 1: Establish a large and small mouse HAPC model in a simulated high-altitude chamber; Step 2: Set up high-dose and low-dose WY pill groups, and use 0.2 mL of tail vein micro-volume blood to perform microRNA detection of erythrocytes, hemoglobin, hematocrit, lactate, erythropoietin, hypoxia-inducible factor-1α, and HIF-1α directly induced by microfluidic chip in one step; Step 3: Construct an "anti-HAPC index" using standardized scores of six indicators, and establish an NIR-PLSR model to achieve 15-second non-destructive prediction; Step 4: Calculate the ED50 of high and low doses using the Emax model. A significant dose-response relationship is determined when the ratio of high to low dose ED50 is ≥3. Step 5: If hypoxia-inducible factor-1α↓≥30%, erythropoietin↓≥25%, miR-210↑≥40%, SOD↑≥20%, and MDA↓≥20%, then WY pills are automatically determined to exert their anti-HAPC effect through the "microRNA axis directly induced by hypoxia-inducible factor-1α-erythropoietin-HIF-1α".
[0030] In this embodiment, the NIR spectral acquisition conditions are: 1000-2500 nm, resolution 2 cm⁻¹, fiber optic probe distance from sample 2 mm, integration time 10 ms. The micro-blood chip is made of polymethyl methacrylate (PMMA) through one-time injection molding and has built-in impedance microelectrodes, lactase membrane, ELISA microcell and qRT-PCR reaction chamber. The qRT-PCR is a technology that adds fluorescent groups to traditional PCR and monitors the amplification products in real time through fluorescence signals to achieve precise quantification of the starting template.
[0031] In summary, this invention achieves efficient integrated storage of different types of data by intelligently analyzing data features, mining semantic relationships between data, and dynamically optimizing storage strategies. Furthermore, it rationally allocates storage resources based on data value and access needs, using high-cost, high-performance storage for critical data and low-cost storage for less important data, thereby improving the overall performance of the storage system. Data compression is achieved by re-encoding data using specific algorithms, reducing data storage space and significantly saving costs.
[0032] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, and not to limit them. Although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some or all of the technical features. Such modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the scope of the technical solutions of the embodiments of the present invention, and they should all be covered within the scope of the claims and specification of the present invention.
Claims
1. A method for preparing a 25-ingredient amla pill for the prevention and treatment of high-altitude polycythemia, characterized in that, include: S1. Study the source of medicinal materials and establish a dual-standard spectral library method for control medicinal materials and counterfeit products; S2. Parameterization and verification of the processing technology of medicinal slices; S3. Online NIR control of the pulverizing-mixing-sterilization process; S4. Use near-infrared principal component analysis to quickly screen finished or semi-finished products and simultaneously quantify key drug components. S5, Data Fusion and Batch Release.
2. The method for preparing the Twenty-Five Flavor Phyllanthus Pill for the prevention and treatment of high-altitude polycythemia as described in claim 1, characterized in that: The establishment of the research on the source of medicinal materials includes multiple source medicinal materials such as Phyllanthus emblica, Meconopsis thunbergii, and Trichosanthes kirilowii seeds. The source is fixed by dual identification through HPLC-DAD / ITS2 barcode and combined with the frequency of clinical use in Tibetan medicine. If a second source needs to be introduced, it is fixed at a weight ratio of 7:3 and traced in the production batch record. For mineral medicines, specify the type, group, ore name or rock name of the mineral, as well as its main components.
3. The method for preparing the Twenty-Five Flavor Phyllanthus Pill for the prevention and treatment of high-altitude polycythemia as described in claim 2, characterized in that: The method for establishing a dual-standard chromatographic library of reference medicinal materials and counterfeit products includes, for easily confused medicinal materials, firstly using thin-layer chromatography to screen out the chemical and chromatographic dual indicators that have the greatest differences and are stable, wherein the chemical indicator is the peak area ratio of two characteristic components, and the chromatographic indicator is a specific spot, requiring a fixed Rf value and distinct color characteristics; The peak ratio R was determined for a large number of representative samples, and the critical value R0 was determined by ROC curve or 95% confidence interval. For the specific spot M, confirm its detection limit. A positive result is defined as clearly visible and with an Rf value consistent with the control, while a negative result is defined as no corresponding spot or an intensity less than the detection limit. If R is less than or equal to R0 and M is negative, it is classified as a chemical indicator; if R is greater than R0 or M is positive, it is classified as a chromatographic indicator. Cross-validation, blind sample testing, and verification by different laboratories were employed to ensure reproducibility; the stability of R0 and M spots was periodically verified using control medicinal materials.
4. The method for preparing the Twenty-Five Flavor Phyllanthus Pill for the prevention and treatment of high-altitude polycythemia as described in claim 1, characterized in that: The online NIR control of the pulverization-mixing-sterilization process includes a particle size model, a mixing uniformity model, and a moisture and sterilization coupling model. The particle size model uses discriminant analysis to lock the 10–80 mesh range. The uniformity model uses a ternary system as a tracer and a moving window F test to capture the mixing endpoint in real time. The moisture model uses the 1940 nm absorption peak as a gate and links it to the sterilization process.
5. The preparation method of the Twenty-Five Flavor Phyllanthus Pill for the prevention and treatment of high-altitude polycythemia as described in claim 4, characterized in that: All particle size models, mixing uniformity models, and moisture and sterilization coupling models share the same hardware configuration: fiber optic probe at a distance of 2 mm from the sample, integration at 10 ms, and full-band acquisition at 1000–2500 nm. Spectral thresholds are set for each critical quality attribute (CQA). Granularity prediction error RSD is less than 5%; If the uniformity similarity is greater than or equal to 0.985, stop the propeller. Only products with a moisture content of 8% or less are allowed to undergo ethylene oxide sterilization, and the residual moisture content after sterilization is 0.1 ppm or less.
6. The method for preparing the Twenty-Five Flavor Phyllanthus Pill for the prevention and treatment of high-altitude polycythemia as described in claim 4, characterized in that: The method for rapid screening of finished or semi-finished products using near-infrared principal component analysis is as follows: 30 pills are randomly selected from each batch, crushed, and placed in a rotating sample cup. The near-infrared full spectrum is acquired with one click. A 99% confidence control limit is set using the Hotelling T² statistic. Any abnormal point deviating from the confidence ellipse will immediately trigger an audible and visual alarm.
7. The method for preparing the Twenty-Five Flavor Phyllanthus Pill for the prevention and treatment of high-altitude polycythemia as described in claim 6, characterized in that: The simultaneous quantification of key drug components includes, A1 efficacy anchor gallic acid: conventional HPLC-UV (280nm, C18 gradient elution) was used, with a lower limit of ≥12 mg / pill to ensure effective dosage; A2 safety anchor aristolochic acid: Highly sensitive UPLC-MS / MS (MRM 359→296) was used, with an upper limit set at ≤0.10 µg / pill to ensure that the toxicity threshold is far below regulatory requirements; A3 uses TLC-bioautoradiography as a secondary verification method to construct a "chemical-activity" dual spectrum: eight characteristic medicinal materials, including Phyllanthus emblica, Meconopsis, Dalbergia odorifera, Lithospermum erythrorhizon, Aucklandia lappa, Aristolochia debilis, Trichosanthes kirilowii seeds, and Carthamus tinctorius, were selected to prepare a mixed control medicinal material accompanying plate; after development under the same chromatographic conditions, the spots were first located with visible / ultraviolet light, and then the antioxidant active spots were displayed by DPPH bioautoradiography.
8. The method for preparing the Twenty-Five Flavor Phyllanthus Pill for the prevention and treatment of high-altitude polycythemia as described in claim 1, characterized in that: The data fusion and batch release includes inputting all data from S1 to S4 into the MES system and generating a QR code. A multivariate statistical process control model was established. The product could only be released when particle size, moisture, uniformity, gallic acid, and aristolochic acid were all within the Hotelling T2 95% control limit and the microorganisms met the control requirements for Tibetan medicine preparations.
9. A method for detecting the Twenty-Five Flavor Phyllanthus Pill for the prevention and treatment of high-altitude polycythemia, based on the preparation method of the Twenty-Five Flavor Phyllanthus Pill for the prevention and treatment of high-altitude polycythemia as described in any one of claims 1 to 8, characterized in that: include, Step 1: Establish a large and small mouse HAPC model in a simulated high-altitude chamber; Step 2: Set up high-dose and low-dose WY pill groups, and use 0.2 mL of tail vein micro-volume blood to perform microRNA detection of erythrocytes, hemoglobin, hematocrit, lactate, erythropoietin, hypoxia-inducible factor-1α, and HIF-1α directly induced by microfluidic chip in one step; Step 3: Construct an "anti-HAPC index" using standardized scores of six indicators, and establish an NIR-PLSR model to achieve 15-second non-destructive prediction; Step 4: Calculate the ED50 of high and low doses using the Emax model. A significant dose-response relationship is determined when the ratio of high to low dose ED50 is ≥3. Step 5: If hypoxia-inducible factor-1α↓≥30%, erythropoietin↓≥25%, miR-210↑≥40%, SOD↑≥20%, and MDA↓≥20%, then WY pills are automatically determined to exert their anti-HAPC effect through the "microRNA axis directly induced by hypoxia-inducible factor-1α-erythropoietin-HIF-1α".
10. The detection method for the Twenty-Five Flavor Phyllanthus Pill for the prevention and treatment of high-altitude polycythemia as described in claim 9, characterized in that: The NIR spectral acquisition conditions are: 1000-2500 nm, resolution 2 cm⁻¹, fiber optic probe distance from sample 2 mm, integration time 10 ms. The micro-blood chip is made of polymethyl methacrylate (PMMA) through one-time injection molding and has built-in impedance microelectrodes, lactase membrane, ELISA microcell and qRT-PCR reaction chamber. The qRT-PCR is a technology that adds fluorescent groups to traditional PCR and monitors the amplification products in real time through fluorescence signals to achieve precise quantification of the starting template.