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CN-122016700-A - Preparation and detection methods of twenty-five-ingredient phyllanthus emblica pills for preventing and treating altitude erythrocytosis

CN122016700ACN 122016700 ACN122016700 ACN 122016700ACN-122016700-A

Abstract

The invention relates to the technical field of traditional Chinese medicine compound preparations, and discloses a twenty-five-flavor phyllanthus emblica pill preparation and detection method for preventing and treating altitude erythrocytosis, which comprises the steps of researching medicinal material base sources, establishing a comparison medicinal material-pseudo-product double-standard graph library method, parameterizing and verifying decoction piece processing technology, performing NIR on-line control in a crushing-mixing-sterilizing process, rapidly screening finished products or semi-finished products by utilizing near infrared principal component analysis, synchronously quantifying key components of medicines, and performing data fusion and batch release.

Inventors

  • GAO FEI
  • JI YUZHE
  • GAO XIANG
  • SUO LANG

Assignees

  • 西藏金仑藏药开发有限公司

Dates

Publication Date
20260512
Application Date
20260227

Claims (10)

  1. 1. A preparation method of twenty-five-ingredient phyllanthus emblica pills for preventing and treating altitude erythrocytosis, which is characterized by comprising the following steps: s1, researching a medicinal material basic source and establishing a comparison medicinal material-counterfeit double-standard graph spectrum library method; s2, parameterizing and verifying a decoction piece processing technology; s3, NIR online control of the crushing-mixing-sterilizing process; S4, rapidly screening finished products or semi-finished products by utilizing near infrared principal component analysis, and synchronously quantifying key components of the medicine; s5, data fusion and batch release.
  2. 2. The preparation method of the twenty-five fructus phyllanthi pill for preventing and treating altitude erythrocytosis of claim 1, wherein the establishment of the preparation method is characterized in that the establishment of the preparation method is used for researching medicinal material base sources, wherein the establishment comprises the steps of carrying out dual identification on multi-base crude medicines such as fructus phyllanthi, artemisia rupestris, fructus polygoni multiflori and the like through HPLC-DAD/ITS2 bar codes, combining clinical use frequency of Tibetan medicine, fixing a unique base source, and if a second base source is required to be introduced, fixing according to a weight ratio of 7:3, and tracing the source in a production batch record; the class, family, ore name or rock name of the mineral is defined for a mineral drug.
  3. 3. The preparation method of the twenty-five phyllanthus emblica pills for preventing and treating altitude erythrocytosis, as set forth in claim 2, characterized in that the establishment of a comparison medicinal material-pseudo product double-standard graph spectrum library method comprises screening out chemical and chromatographic double indexes which have the largest difference and stably exist by a thin-layer chromatography means aiming at confusing medicinal materials, wherein the chemical indexes are peak area ratios of two characteristic components, the chromatographic indexes are exclusive spots, and Rf values are required to be fixed and color development characteristics are clear; determining a peak ratio R for a plurality of representative samples, determining a critical value R 0 with ROC curves or 95% confidence intervals; For the exclusive spot M, confirming the detection limit, defining positive as obvious visible and Rf value consistent with the control, and negative as no corresponding spot or intensity less than the detection limit; If R is less than or equal to R 0 and M is negative, the chemical index is classified, and if R is more than R 0 or M is positive, the chemical index is classified as a chromatographic index; The reproducibility is ensured by adopting cross verification, blind sample examination and rechecking in different laboratories, and the stability of R 0 and M spots is checked by using reference medicinal materials at regular intervals.
  4. 4. The preparation method of the twenty-five phyllanthus emblica pills for preventing and treating altitude erythrocytosis, as set forth in claim 1, is characterized in that the NIR on-line control of the crushing-mixing-sterilizing process comprises a particle size model, a mixing uniformity model and a water and sterilization coupling model, wherein the particle size model is used for locking a 10-80 mesh interval by discriminant analysis, the uniformity model adopts a ternary system as a tracer, a moving window F test captures a mixing endpoint in real time, and the water model adopts a 1940 nm absorption peak as a gate to link a sterilizing process.
  5. 5. The method for preparing the twenty-five phyllanthus emblica pills for preventing and treating altitude erythrocytosis according to claim 4, wherein all particle size models, mixed uniformity models, water and sterilization coupling models share the same hardware configuration, the optical fiber probe is used for collecting whole wave bands of sample 2mm, integral 10ms and 1000-2500 nm, and each key quality attribute CQA is set with a spectral threshold value: the granularity prediction error RSD is less than 5%; The uniformity similarity is more than or equal to 0.985, namely Rowed of all; and the water content is less than or equal to 8 percent, and then the water enters ethylene oxide for sterilization, and the residual water after sterilization is less than or equal to 0.1 ppm.
  6. 6. The preparation method of the twenty-five phyllanthus emblica pills for preventing and treating altitude erythrocytosis, as set forth in claim 4, is characterized in that the method for rapidly screening finished products or semi-finished products by utilizing near infrared principal component analysis is that 30 pills are randomly taken from each batch, crushed and placed in a rotary sample cup, near infrared full spectrum is collected by one key, 99% confidence control limit is set through Hotelling T2 statistics, and sound light alarm is immediately triggered at abnormal points deviating from confidence ellipses.
  7. 7. The method for preparing the twenty-five phyllanthus emblica pills for preventing and treating altitude erythrocytosis according to claim 6, wherein the step of synchronously quantifying the key components of the medicine comprises, A1 efficacy anchor point gallic acid adopts conventional HPLC-UV (280 nm, C18 gradient elution), and the lower limit is set to be more than or equal to 12 mg per pill, so that the effective dosage is ensured; A2, the safe anchor aristolochic acid adopts high-sensitivity UPLC-MS/MS (MRM 359- & gt 296), and the upper limit is set to be less than or equal to 0.10 mug/pill, so that the toxicity threshold value is ensured to be far lower than the regulation requirement; A3, taking TLC-biological self-development as a side surface to construct a chemical-active dual-map, namely 8 characteristic medicinal materials including phyllanthus emblica, artemisia rupestris, rosewood heart wood, shikonin, elecampane, aristolochia, polygonum multiflorum and safflower are selected to prepare a mixed control medicinal material following plate, after the mixed control medicinal material following plate is developed under the same chromatographic condition, the color spots are positioned by visible light/ultraviolet light, and then the DPPH biological self-development is used for showing the antioxidant active spots.
  8. 8. The preparation method of the twenty-five phyllanthus emblica pills for preventing and treating altitude erythrocytosis, as set forth in claim 1, is characterized in that the data fusion and batch release comprises the steps of inputting all data of S1-S4 into an MES system to generate a two-dimensional code; A multivariate statistical process control model is established, and when granularity, moisture, uniformity, gallic acid and aristolochic acid are simultaneously within a control limit of Hotelling T2% and microorganisms meet the control bacteria requirement of the Tibetan medicine preparation, the recipe can be released.
  9. 9. The twenty-five-flavor phyllanthus emblica pill detection method for preventing and treating altitude erythrocytosis is based on the twenty-five-flavor phyllanthus emblica pill preparation method for preventing and treating altitude erythrocytosis of any one of claims 1-8, and is characterized by comprising the following steps of, Step one, establishing a large and small mouse HAPC model in a simulated plateau cabin; Step two, setting a high-dose WY pill group and a low-dose WY pill group, adopting 0.2 mL tail vein trace blood, and completing micro RNA detection directly induced by erythrocytes, hemoglobin, hematocrit, lactic acid, erythropoietin, hypoxia inducible factor-1 alpha and HIF-1 alpha through a microfluidic chip at one time; Thirdly, establishing an anti-HAPC index by using six index standardization scores, and establishing an NIR-PLSR model to realize 15s nondestructive prediction; Calculating the ED50 of the high and low doses by adopting an Emax model, and judging that a significant dose-effect relationship exists when the ED50 ratio of the high and low doses is more than or equal to 3; Step five: if hypoxia induction factor-1α +≥30%, erythropoietin +≥25%, miR-210 +≥40%, SOD +≥20% and MDA +≥20%, it is automatically determined that WY pill plays an anti-HAPC role through the microRNA axis directly induced by hypoxia induction factor-1α -erythropoietin-HIF-1α.
  10. 10. The method for detecting the twenty-five phyllanthus emblica pills for preventing and treating altitude erythrocytosis according to claim 9, wherein the NIR spectrum acquisition condition is 1000-nm, the resolution is 2-cm-1, the optical fiber probe is away from a sample 2 mm, the integration time is 10-ms, the microchips are formed by one-time injection molding of polymethyl methacrylate (PMMA), impedance microelectrodes, a lactate membrane, an ELISA micro-cell and a qRT-PCR reaction cavity are built in, fluorescent groups are added on the basis of traditional PCR, and amplification products are monitored in real time through fluorescent signals, so that the technology for accurately quantifying an initial template is realized.

Description

Preparation and detection methods of twenty-five-ingredient phyllanthus emblica pills for preventing and treating altitude erythrocytosis Technical Field The invention relates to the technical field of traditional Chinese medicine compound preparations, in particular to a preparation and detection method of twenty-five fructus phyllanthi pills for preventing and treating altitude erythrocytosis. Background With the rapid development of the traditional Chinese medicine industry, the safety and quality stability of traditional Chinese medicine products become key factors influencing the development of traditional Chinese medicines, so that the quality control of the whole process of the traditional Chinese medicine industry is widely focused under the large environment of the construction of the national standardization system. Meanwhile, as the national drug administration issues new drugs with improved functions and indications in the requirements of traditional Chinese medicine registration classification and reporting data, the new way of development of drug enterprises is widened, in recent years, as Tibetan drugs are widely focused, twenty-five-ingredient emblic leafflower pills are increasingly applied to clinic, and compound preparations prepared from twenty-six medicinal materials such as emblic leafflower fruits, babaka, artificial bezoar and azure blue are prescribed, and are clinically used for treating chest and back fullness, liver and gall pain, hoarseness conjunctival congestion, oral and labia purple and irregular menstruation caused by hypertension and hyperlipidemia. Based on the concept of 'quality source design', in the research process of adding new indications, the production process parameters of the traditional Chinese medicine are checked from the research source, because the quality variation of the raw materials, the fluctuation of the process parameters, the strict quality monitoring standard and the lack of an effective monitoring method all cause the difference of the product quality among different batches. In order to ensure the stability and uniformity of the quality of the final product, a reasonable quality standard is established aiming at key control points of the production process, and an effective detection method is researched to realize the control of the whole production process. As the production unit of the medicine, the construction of the whole process quality control system is particularly important, the production of Tibetan medicines has been greatly developed and advanced in recent years, the indexes of internal control detection chemical components are increased for most varieties of preparations, along with the standardization of the drug re-registration work of the Tibetan autonomous region and the improvement of the supervision force of Chinese patent medicines, the continuous development of the drug re-registration work of the Tibetan medicines is also consistent with the production of Tibetan medicines of different varieties in different manufacturers, so that the situation that the prescription composition, the Tibetan medicine sources and the processing processes are different from each other and the quality control is difficult to be performed in a unified standard is broken, and the situation that the medicine manufacturers need to perform single variety of systematic researches on the basic sources and the detection of the medicinal materials, the processing processes and the quality control of the medicinal materials, the semi-finished products, the finished product preparation processes and the quality control and related heavy metals and bacteria from the medicinal material sources is important. Disclosure of Invention Aiming at the defects in the prior art, the invention provides a preparation method of twenty-five-ingredient phyllanthus emblica pills for preventing and treating altitude erythrocytosis, which comprises the following steps of S1, researching medicinal material basic sources and establishing a comparison medicinal material-counterfeit double-standard graph spectrum library method; s2, parameterizing and verifying a decoction piece processing technology; s3, NIR online control of the crushing-mixing-sterilizing process; S4, rapidly screening finished products or semi-finished products by utilizing near infrared principal component analysis, and synchronously quantifying key components of the medicine; s5, data fusion and batch release. Further, the establishment of the research on the medicinal material base sources comprises the steps of carrying out double identification on multi-base crude medicines such as phyllanthus emblica, artemisia rupestris, polygonum multiflorum and the like through HPLC-DAD/ITS2 bar codes, combining clinical use frequency of Tibetan medicine, fixing a unique base source, if a second base source is required to be introduced, fixing according to a weight ratio of 7:3, and tracing the source in a product