Whole-process quality control and preparation technology of soluble mercury arsenic in an nao pill

Abstract

The present application is suitable for the technical field of traditional Chinese medicine preparation and quality control, and provides a whole-process quality control and preparation process of soluble mercury arsenic in Annao pills, establishes a triple-progressive whole-process quality control system of soluble mercury arsenic, which is raw material source control-preparation process control-finished product final inspection traceability: the first level is special detection of cinnabar and realgar raw materials and water fly process control, to reduce the introduction of soluble mercury arsenic from the source; the second level is accurate control of pretreatment and key process parameters of preparation, to inhibit the generation of soluble mercury arsenic through standardizing drying, crushing, sterilization, refining honey and other steps; the third level is the combination of finished product legal standard inspection and special detection, to realize whole-process quality traceability; the present application can ensure that the content of arsenic trioxide in Annao pills meets the legal standard, at the same time, ensure that the content of effective components such as borneol and menthol meets the standard, control the weight difference between batches within the legal range, and make the dissolution time limit and moisture meet the requirements, so as to comprehensively improve the quality safety and stability of Annao pills.

Description

Technical Field

[0001] This invention belongs to the field of traditional Chinese medicine preparation and quality control technology, and particularly relates to the whole process quality control and preparation process of soluble mercury and arsenic in Annaowan. Background Technology

[0002] Annao Pills are a traditional Chinese medicine preparation developed based on classic formulas. They possess the effects of clearing heat and detoxifying, refreshing the mind and calming the nerves, resolving phlegm and opening the orifices, and calming the nerves and extinguishing wind. Clinically, they are widely used for symptoms such as high fever with delirium, irritability and incoherent speech, convulsions, stroke with blocked orifices, headache and dizziness. They also have a clear therapeutic effect on symptoms related to hypertension and stroke. Compared with similar emergency Chinese medicines, Annao Pills focus more on daily treatment and symptom control, have a wider range of applicable populations, and a longer treatment period; therefore, their quality and safety are particularly important.

[0003] The prescription for Annaowan contains two traditional mineral medicines: cinnabar and realgar. These two medicines play important therapeutic roles in traditional Chinese medicine theory, but they also pose certain safety risks. Cinnabar's main component is mercuric sulfide, and realgar's main component is arsenic disulfide. Both compounds have extremely low solubility in the human body and relatively low toxicity. However, during the mining and processing of these raw materials, as well as during the preparation of the medicine, environmental factors and process conditions may produce soluble mercury and arsenic ions. These soluble heavy metal ions are highly toxic and can be absorbed by the human body. Long-term or excessive intake can cause irreversible damage to vital organs such as the nervous system, digestive system, and kidneys, and in severe cases, can even be life-threatening.

[0004] Currently, although the production and quality control system of Annaowan is relatively complete, there are still some shortcomings in the control of soluble mercury and arsenic:

[0005] The raw material quality control system is inadequate, and the ability to control at the source is insufficient: Current raw material testing mainly focuses on determining the content of the main components in cinnabar and realgar, with insufficient emphasis on specialized testing of soluble mercury and arsenic components that directly affect the safety of the finished product. Many manufacturers only conduct routine physical and identification checks on raw materials, failing to include the content of divalent mercury, trivalent arsenic, and pentavalent arsenic as mandatory testing items. If the content of these soluble toxic components in the raw materials is too high, it is difficult to completely remove them through subsequent formulation processes alone, thus posing a potential safety hazard to the finished product.

[0006] The quality control points in the preparation process are scattered, lacking systematic process control: The preparation process of Annaowan is complex, involving multiple steps such as pretreatment, total mixing, and formulation. The process parameters of each step can affect the content of soluble mercury and arsenic. For example, excessively high drying temperature, excessively long sterilization time, and heat generated during pulverization can all cause changes in the crystal structure of cinnabar and realgar, thereby increasing the dissolution of soluble mercury and arsenic. In the existing production process, the quality control points of each process are relatively independent, and a systematic monitoring network for soluble mercury and arsenic has not been formed, making it difficult to detect and resolve problems that occur in the process in a timely manner.

[0007] The outdated finished product inspection model hinders end-to-end quality traceability: Currently, most companies adopt a "final inspection of finished products" quality control model, meaning quality inspection is only conducted after the finished product has been manufactured. While this model ensures the quality of products leaving the factory, if a defective product is found, the entire batch must be scrapped, resulting in significant economic losses. Furthermore, finished product inspection only reflects the final product's quality status and cannot trace the specific reasons for excessive levels of soluble mercury and arsenic, hindering continuous improvement of production processes and the perfection of the quality system.

[0008] Therefore, the entire process of quality control and preparation technology for soluble mercury and arsenic in Annaowan is needed to solve the above problems. Summary of the Invention

[0009] The purpose of this invention is to provide a complete process for quality control and preparation of soluble mercury and arsenic in Annaowan (a traditional Chinese medicine) to solve the problems mentioned in the background art.

[0010] To achieve the above objectives, the present invention provides the following technical solution:

[0011] The entire process of quality control and preparation technology for soluble mercury and arsenic in Annaowan includes the following steps:

[0012] S1 Raw Material Pretreatment: The 15 medicinal materials in the legal prescription of Annaowan are respectively cleaned, washed, dried, crushed and sterilized. Among them, cinnabar and realgar are processed by water-milling to obtain water-milled powder.

[0013] S2 Total Mixing: The powders of six kinds of herbs and eight kinds of precious and fine herbs are mixed evenly using the equal-volume incremental dilution method to obtain the raw material powder for Annao Pills;

[0014] S3 Preparation: The following steps are performed sequentially: honey refining, honey warming, mixing and fermentation, pill making, coating, packaging, wax sealing and transfer printing to obtain the finished product of Annao Pills;

[0015] S4 full-process quality control includes three stages: raw material testing, intermediate product testing, and finished product testing. Raw material testing focuses on divalent mercury, trivalent arsenic, and pentavalent arsenic in cinnabar and realgar. Intermediate product testing covers all key processes. Finished product testing is carried out in accordance with legal quality standards for all items.

[0016] In a further technical solution, step S1, the testing of the cinnabar raw material includes: appearance, identification, iron content inspection, determination of divalent mercury content, and determination of mercuric sulfide content, wherein the divalent mercury content, calculated as mercury, shall not exceed the legal limit, and the mercuric sulfide content shall not be less than the legal requirement; the testing of the realgar raw material includes: appearance, identification, determination of the total content of trivalent and pentavalent arsenic, and determination of arsenic disulfide content, wherein the total content of trivalent and pentavalent arsenic, calculated as arsenic, shall not exceed the legal limit, and the arsenic disulfide content shall not be less than the legal requirement.

[0017] In a further technical solution, in step S1, the cleaning process is carried out on a sorting workbench to remove impurities and non-medicinal parts from Scutellaria baicalensis, Coptis chinensis, Gardenia jasminoides, Curcuma longa, gypsum, and mother-of-pearl; the washing process uses a washing machine to wash the cleaned Scutellaria baicalensis, Coptis chinensis, Gardenia jasminoides, and Curcuma longa at room temperature by spraying with flowing water; the drying process uses a hot air circulating oven to dry for a specified time at a suitable temperature, and the thickness of the material in the drying tray does not exceed the specified value.

[0018] In a further technical solution, in step S1, the pulverizing process uses a hammer mill to pulverize pearl, calcined ochre, and borneol into fine powder, wherein the pearl and calcined ochre pass through a sieve of a specified mesh size, and the borneol passes through a sieve of a specified mesh size; a coarse crusher is used to mix and coarsely crush Scutellaria baicalensis, Coptis chinensis, Gardenia jasminoides, Curcuma longa, mother-of-pearl, and gypsum into coarse powder; and a micro-pulverizer is used to pulverize the above coarse powder into fine powder and pass it through a sieve of a specified mesh size.

[0019] In a further technical solution, in step S1, the sterilization process uses a multi-functional traditional Chinese medicine sterilization cabinet to sterilize the herbal powder and calcined hematite powder. The sterilization temperature, sterilization time, and drying time all meet the specified requirements, and the thickness of the spread material does not exceed the specified value.

[0020] In a further technical solution, step S2, the equal-volume incremental dilution method specifically involves: ① mixing borneol powder with an equal amount of herbal powder and passing it through a sieve of a specified mesh size; mixing a portion of realgar powder with an equal amount of herbal powder; and then mixing the two mixtures together and passing them through a sieve of a specified mesh size; ② mixing the remaining realgar powder with a portion of the herbal powder; mixing calcined ochre powder with pearl powder; premixing artificial bezoar powder with an equal amount of cinnabar powder and then mixing it with the remaining cinnabar powder; and then mixing the three mixtures together and passing them through a sieve of a specified mesh size; ③ alternately adding ①, ②, and a portion of the herbal powder into a mixer and mixing for a specified time; ④ then alternately adding pig bile powder, buffalo horn concentrate powder, and the remaining herbal powder into a mixer and mixing for a specified time.

[0021] A further technical solution, in step S3, the honey refining process refines the honey at a specified temperature and controls the relative density within a specified range; the honey warming process heats the refined honey to a specified temperature; the mixing and resting process mixes the brain pill raw material powder, menthol and warm honey in a specified ratio and stirs for a specified time to make a soft material, and then rests it at room temperature for a specified time.

[0022] In a further technical solution, in step S3, the pill-making process uses a horizontal automatic pill-making machine for traditional Chinese medicine to produce small honey pills of a specified weight. During the pill-making process, the weight difference of the pills is controlled within the warning limit and the correction limit. In the coating process, diluted honey and Annao pill raw material powder are alternately sprinkled on the pills to make the pills round and uniform in appearance and consistent in color.

[0023] In a further technical solution, step S4 includes the following intermediate product testing: degree of cleanliness, degree of washing, degree of drying, fineness of grinding, sterilization effect, uniformity of mixing, quality of soft material, weight difference of pellets, appearance of coating, quality of packaging, quality of wax sealing, and quality of pad printing; the finished product testing includes: properties, identification, arsenic trioxide test, weight difference, dispersibility time, moisture content, content determination, and microbial limits, wherein the arsenic trioxide test meets the legal requirements, and each 1g of finished product contains no less than the legal limit for borneol and menthol.

[0024] Compared with the prior art, the beneficial effects of the present invention are:

[0025] This invention achieves source control of soluble mercury and arsenic, significantly improving the safety of raw materials: a comprehensive special testing system for cinnabar and realgar raw materials has been established, and the content of divalent mercury, trivalent arsenic and pentavalent arsenic is a mandatory testing item for raw materials entering the warehouse, thus preventing raw materials with high soluble mercury and arsenic content from entering the production process from the source. At the same time, the water-milling method is used to process cinnabar and realgar, which can effectively remove most of the soluble mercury salts and arsenic salts in the raw materials.

[0026] This invention establishes a systematic process quality control system, which effectively reduces the generation of soluble mercury and arsenic: all key processes in the preparation of Annaowan are included in the quality control scope, and clear quality control standards and operating procedures are formulated for each process. By strictly controlling process parameters such as drying temperature, sterilization time, and pulverization fineness, changes in the crystal structure of cinnabar and realgar can be effectively avoided, thereby reducing the generation of soluble mercury and arsenic. At the same time, the intermediate product testing link can monitor the product quality of each process in real time, promptly identify and solve problems, and prevent unqualified intermediate products from flowing into the next process.

[0027] This invention enables end-to-end quality traceability, significantly improving product quality stability: A comprehensive quality traceability system is established, with detailed records of information at each stage, including raw material procurement, production process, and finished product inspection. If a problem is found during finished product testing, the specific production stage and raw material batch can be quickly traced back, allowing for timely corrective measures. Simultaneously, the end-to-end quality control system effectively reduces the impact of human factors on product quality and improves consistency between product batches. Experimental results show that the variation range of weight differences, effective ingredient content, and soluble mercury and arsenic content in the brain pills produced using the process of this invention is significantly reduced, resulting in a substantial improvement in product quality stability.

[0028] To more clearly illustrate the structural features and effects of the present invention, the present invention will be described in detail below with reference to the accompanying drawings and specific embodiments. Attached Figure Description

[0029] Figure 1 This is a schematic diagram of the overall process of the present invention. Detailed Implementation

[0030] To make the objectives, technical solutions, and advantages of this invention clearer, the invention will be further described in detail below with reference to the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are merely illustrative and not intended to limit the invention.

[0031] The specific implementation of the present invention will be described in detail below with reference to specific embodiments.

[0032] Example 1

[0033] like Figure 1 As shown, this embodiment of the invention provides a complete process for quality control and preparation of soluble mercury and arsenic in Annaowan (a traditional Chinese medicine), including the following steps:

[0034] S1 Raw Material Pretreatment: The 15 medicinal materials in the legal prescription of Annaowan are respectively cleaned, washed, dried, crushed and sterilized. Among them, cinnabar and realgar are processed by water-milling to obtain water-milled powder.

[0035] S2 Total Mixing: The powders of six kinds of herbs and eight kinds of precious and fine herbs are mixed evenly using the equal-volume incremental dilution method to obtain the raw material powder for Annao Pills;

[0036] S3 Preparation: The following steps are performed sequentially: honey refining, honey warming, mixing and fermentation, pill making, coating, packaging, wax sealing and transfer printing to obtain the finished product of Annao Pills;

[0037] S4 full-process quality control includes three stages: raw material testing, intermediate product testing, and finished product testing. Raw material testing focuses on divalent mercury, trivalent arsenic, and pentavalent arsenic in cinnabar and realgar. Intermediate product testing covers all key processes. Finished product testing is carried out in accordance with legal quality standards for all items.

[0038] This embodiment details the core process flow of the present invention, covering the entire process from raw material processing to finished product preparation. Different processing methods are used for different types of medicinal materials in the raw material pretreatment stage. In particular, cinnabar and realgar are processed using the water-milling method, effectively removing soluble mercury and arsenic from the raw materials. The total mixing stage uses an equal-volume incremental dilution method to ensure the uniformity of the medicinal powder. The preparation stage follows the traditional Chinese medicine pill preparation process to ensure product quality. Full-process quality control is implemented throughout the entire production process, achieving comprehensive monitoring of product quality. The process provided in this embodiment can effectively control the content of soluble mercury and arsenic in Annaowan, ensuring the safety and efficacy of the product.

[0039] Example 2

[0040] The difference between this embodiment and Embodiment 1 is that step S1 further includes a detailed raw material testing step, specifically:

[0041] Cinnabar raw material testing: The cinnabar raw material is tested for its properties, identification, iron content, divalent mercury content, and mercuric sulfide content. The properties test requires the cinnabar to be granular or lumpy aggregates, bright red or dark red, and lustrous. Identification tests are conducted using the copper strip friction method and chemical identification methods. The iron content test requires that the iron content not exceed the legal limit. The divalent mercury content test is performed using liquid chromatography-inductively coupled plasma mass spectrometry (LC-ICP-MS), and the divalent mercury content, expressed as mercury, must not exceed the legal limit. The mercuric sulfide content test is performed using titration, and the mercuric sulfide content must not be less than the legal requirement.

[0042] Testing of Realgar Raw Materials: The raw materials of realgar are subjected to tests for appearance, identification, determination of total trivalent and pentavalent arsenic content, and determination of arsenic disulfide content. Appearance testing requires realgar to be in the form of lumps or granular aggregates, deep red or orange-red, with a diamond-like luster. Identification tests are conducted using chemical identification and heating identification methods. The determination of total trivalent and pentavalent arsenic content is performed using liquid chromatography-inductively coupled plasma mass spectrometry (LC-ICP-MS), and the total content of trivalent and pentavalent arsenic, expressed as arsenic, must not exceed the legal limit. The determination of arsenic disulfide content is performed using titration, and the arsenic disulfide content must not be less than the legal requirement.

[0043] Testing of other Chinese medicinal materials: Raw materials such as Scutellaria baicalensis, Coptis chinensis, Gardenia jasminoides, Curcuma longa, gypsum, mother-of-pearl, artificial bezoar, pig bile powder, concentrated buffalo horn powder, borneol, and menthol are tested in accordance with legal standards and can only be used after passing the tests.

[0044] This embodiment details the specific items and methods for raw material testing, particularly adding specific testing for divalent mercury in cinnabar and trivalent and pentavalent arsenic in realgar. By strictly controlling the quality of raw materials, unqualified raw materials can be prevented from entering the production process at the source, effectively reducing the content of soluble mercury and arsenic in the finished product. The raw material testing method provided in this embodiment is accurate and reliable, and can meet the quality control requirements for the production of Annaowan.

[0045] Example 3

[0046] The difference between this embodiment and embodiment 2 is that step S1 further includes detailed pretreatment process parameters, specifically:

[0047] Cleaning: The medicinal materials are cleaned on the sorting workbench to remove impurities and non-medicinal parts from Scutellaria baicalensis, Coptis chinensis, Gardenia jasminoides, Curcuma longa, gypsum, and mother-of-pearl. The cleaned medicinal materials are placed in clean containers and labeled for later use.

[0048] Cleaning: Use a washing machine to clean the selected Scutellaria baicalensis, Coptis chinensis, Gardenia jasminoides, and Curcuma longa. The cleaning method is running water spraying. The water used for cleaning is drinking water at room temperature. Wash until there is no mud or sand on the surface of the herbs and the water is clear. The water used should not be used to wash other herbs, and different herbs should not be washed together.

[0049] Drying: The cleaned Scutellaria baicalensis, Coptis chinensis, Gardenia jasminoides, and Curcuma longa are dried in a hot air circulating oven. The thickness of the material in the drying tray does not exceed the specified value, the drying temperature is controlled within a suitable range, and the drying time is the specified time. During the drying process, the degree of dryness of the medicinal materials is checked regularly. The dried medicinal materials should maintain a bright color and feel dry to the touch.

[0050] Crushing: A hammer mill is used to crush pearl, calcined hematite, and borneol into fine powder, with pearl and calcined hematite passing through a sieve of a specified mesh size, and borneol passing through a sieve of a specified mesh size; a coarse crusher is used to mix and coarsely crush Scutellaria baicalensis, Coptis chinensis, Gardenia jasminoides, Curcuma longa, mother-of-pearl, and gypsum into coarse powder; a micro-grinding unit is used to crush the above coarse powder into fine powder and pass it through a sieve of a specified mesh size; the tailings generated during the crushing process are collected and added to the next batch for use.

[0051] Sterilization: The herbal powder and calcined hematite coarse powder are sterilized using a multi-functional Chinese medicine sterilization cabinet; the materials are spread in a tray, with the thickness not exceeding the specified value, the sterilization temperature is controlled at the specified value, the sterilization time is the specified time, and the drying time is the specified time; after sterilization, the materials are cooled to room temperature and placed in a clean container, labeled and ready for use.

[0052] In this embodiment, the process parameters and operational requirements for each pretreatment step are specified in detail. By strictly controlling the process parameters of steps such as purification, washing, drying, pulverizing, and sterilization, the quality of intermediate products in the pretreatment can be effectively guaranteed, while reducing the generation of soluble mercury and arsenic during the preparation process. For example, controlling the drying temperature within a suitable range can prevent the decomposition of cinnabar and realgar caused by high temperatures. Controlling the fineness of pulverization can ensure the uniformity of the powder, which is beneficial for subsequent mixing and formulation. The pretreatment process parameters provided in this embodiment have been verified through production practice and can meet the requirements for large-scale production of Annaowan.

[0053] Example 4

[0054] The difference between this embodiment and embodiment 3 is that step S2 further includes a detailed mixing process, specifically:

[0055] Pre-mixing weighing: Weigh each of the six herbal powders and eight precious medicinal powders (artificial bezoar powder, borneol powder, pearl powder, cinnabar powder, calcined hematite powder, realgar powder, pig bile powder, and concentrated buffalo horn powder) according to the batch production instructions. The weighing process is double-checked to ensure accuracy. Realgar powder is a toxic medicinal material and should be weighed under the supervision of a designated person using special containers and weighing instruments. Necessary protective measures should be taken during the weighing process to prevent dust from flying.

[0056] General Mixing: Except for menthol, mix the six herbal powders and eight precious medicinal powders according to the following steps:

[0057] ① Mix borneol powder with an equal amount of herbal powder and pass through a sieve of the specified mesh size. Mix some realgar powder with an equal amount of herbal powder. Combine the two mixtures and pass through a sieve of the specified mesh size.

[0058] ② Mix the remaining realgar powder with some herbal powder, mix calcined hematite powder with pearl powder, premix artificial bezoar powder with an equal amount of cinnabar powder, and then mix with the remaining cinnabar powder. Mix the three powders together and pass them through a sieve of the specified mesh size.

[0059] ③ Add the mixed powder obtained in steps ① and ②, along with a portion of the herbal powder, into the mixer alternately and mix for the specified time;

[0060] ④ Next, add the pig bile powder, buffalo horn concentrate, and the remaining herbal powder into the mixer in a crosswise manner, and mix for the specified time.

[0061] Post-mixing processing: The mixed Anaonaowan raw material powder is placed in a clean container. Each container should be labeled with the name, batch number, quantity, operator, date, etc. The process engineer fills out an inspection request form, and the quality inspector takes samples for inspection. After passing the inspection, it is put into use.

[0062] In this embodiment, the specific steps and operational requirements of the total mixing process are specified in detail. The use of an equal-volume incremental dilution method for mixing ensures that small amounts of precious medicinal powders, especially cinnabar and realgar, are evenly distributed in a large amount of herbal powder, avoiding the problem of excessively high local concentrations. At the same time, stepwise mixing and sieving can further improve the mixing uniformity of the medicinal powder. The total mixing process method provided in this embodiment can effectively ensure the uniformity of the raw material powder of Annaowan, thereby ensuring the consistency of the content of each component in the finished product.

[0063] Example 5

[0064] The difference between this embodiment and Embodiment 4 is that step S3 further includes detailed formulation preparation process parameters, specifically:

[0065] Preparation of raw materials for formulation: Obtain raw materials such as Annaowan powder, menthol and refined honey according to the batch production order, check the name, batch number and quantity of materials and the inspection report, and set them aside after confirming that they are correct.

[0066] Honey refining: Put the honey into a honey refining pot and heat it for refining; control the honey refining temperature within the specified range and control the relative density of the honey at around the specified value; stir constantly during the honey refining process to prevent the honey from caramelizing; store the refined honey in an airtight container for later use.

[0067] Warm honey: Heat the refined honey to the specified temperature and keep it warm for later use.

[0068] Mixing and resting: First, weigh the warmed refined honey according to the specified ratio, add the weighed menthol, and stir evenly; then put the weighed Annaowan raw material powder into the mixer and stir it together with the refined honey containing menthol for the specified time to make a soft material; the soft material should have no dry powder on the surface, be moist inside and out, have a uniform color, and be of moderate softness and hardness, and be able to be easily shaped; divide the soft material into appropriately sized pieces, place them on a stainless steel plate, and let them rest at room temperature for the specified time.

[0069] Pill making: A horizontal automatic pill making machine for Chinese medicine is used for pill making; the prepared soft material is filled into the feed inlet, and the thickness of the pill strips is adjusted to make the pills uniform in size and weight; during the pill making process, the pills are sampled at any time for weight check, and the weight difference of the pills is controlled within the warning limit and correction limit; unqualified pills are picked out in time, and the pill making tail material is incorporated into the subsequent batching process for recycling.

[0070] Coating: Select qualified pills after pill making and put them into the coating pot; sprinkle the refined honey and the raw material powder of Anao Pills alternately and evenly on the pills to make the pills round, uniform, delicate and moist, and with a consistent color; randomly select a certain number of pills from each batch to check the weight difference, and if they meet the requirements, they can be discharged.

[0071] Repackaging: The qualified coated pills are repackaged, with 11 pills per polyethylene pill shell, which is sealed tightly; quality inspectors will randomly check the filling amount and the tightness of the shell at any time.

[0072] Wax sealing: The packaged spheres are sealed with wax using a fully automatic large honey pill wax dipping machine; the wax temperature is controlled within the specified range, 3-4 layers of wax are applied, and the wax seal should be uniform and tight, resulting in a smooth sphere shape.

[0073] Pad printing: The product name is printed on the wax-sealed sphere shell using a fully automatic pad printing machine. The printed characters should be clear and complete. The printed product is the medicine to be packaged and is stored in the warehouse for inspection after being attached to the storage location card.

[0074] In this embodiment, the process parameters and operational requirements for each step of the preparation are specified in detail. By strictly controlling process parameters such as honey refining temperature, mixing time, and pelleting speed, high-quality Annao Pills can be prepared. At the same time, a series of measures are taken during the preparation process to reduce the generation of soluble mercury and arsenic. For example, the honey refining temperature is controlled within a suitable range to avoid the decomposition of cinnabar and realgar due to high temperature. Automated pelleting equipment is used to improve the uniformity of the pellets. The preparation process parameters provided in this embodiment have been verified through production practice and can meet the requirements for large-scale production of Annao Pills.

[0075] Example 6

[0076] The difference between this embodiment and embodiment 5 is that step S4 further includes a detailed full-process quality control method, specifically:

[0077] Raw material testing: All raw materials shall be tested according to the method specified in Example 2, and a raw material quality file shall be established; unqualified raw materials shall be returned and shall not be used in production.

[0078] Intermediate product testing: Comprehensive testing is conducted on intermediate products from each stage of pretreatment and formulation. Testing items include:

[0079] Cleaned intermediate products: The degree of cleanliness is tested, requiring the absence of impurities and non-pharmaceutical parts;

[0080] Cleaning intermediate products: Check the degree of cleanliness, requiring that the chemicals be completely removed and the water be clear;

[0081] Dry intermediate products: To test the degree of dryness, the medicinal materials should have a bright color and feel dry to the touch;

[0082] Grinding intermediate products: Test the fineness of the grinding, which must meet the sieve mesh requirements of each material;

[0083] Sterilized intermediate products: Microbial limits must be tested and compliance with regulations is required;

[0084] Intermediate product from total mixture: Test the uniformity of mixing, requiring the powder to have a uniform and consistent color;

[0085] Intermediate products from the composite material: The quality of the soft material must be tested, requiring no dry powder on the surface, complete moisture inside and out, consistent color, and moderate softness and hardness;

[0086] intermediate pelleting products: inspect pellet weight variation and appearance, requiring pellet weight to meet the warning limit and correction limit requirements, and the appearance to be round and uniform;

[0087] Intermediate coated products: Inspect the appearance of the coating, requiring it to be round and uniform, delicate and moist, and with consistent color;

[0088] Sub-packaging of intermediate products: Testing the filling volume and the tightness of the shells, requiring 11 pellets to be filled in each shell and tightly sealed;

[0089] Wax-sealed intermediate products: Inspect the quality of the wax seal, requiring uniform and tight sealing, and smooth spherical shape;

[0090] Intermediate products in pad printing: Inspect the quality of the printed text, requiring it to be clear and complete.

[0091] Finished product testing: The finished product is subjected to full-item testing in accordance with the statutory quality standards. The testing items include appearance, identification, arsenic trioxide test, weight difference, dissolution time limit, moisture, content determination and microbial limit. Among them, the arsenic trioxide test is carried out by the arsenic salt test method, and the color of the arsenic spot shown must not be darker than the standard arsenic spot. The content determination is carried out by gas chromatography, and the content of borneol and menthol per 1g of finished product must not be less than the statutory limit.

[0092] Quality Traceability: Establish a comprehensive quality traceability system to record information in detail at every stage, including raw material procurement, production process, and finished product inspection. All records should be true, accurate, and complete, and should be kept for one year after the product's expiration date. If problems are found during finished product testing, the specific production stage and raw material batch can be quickly traced through the quality traceability system, allowing for timely corrective measures.

[0093] This embodiment details the specific methods and requirements for full-process quality control; by establishing a three-level quality control system covering raw materials, intermediate products, and finished products, quality monitoring of the entire production process of Annaowan is achieved; at the same time, a sound quality traceability system can ensure the traceability of product quality and provide data support for continuous improvement of production processes; the full-process quality control method provided in this embodiment can effectively ensure the quality and safety of Annaowan and improve the market competitiveness of the product.

[0094] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, and improvements made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. The whole-process quality control and preparation process of soluble mercury and arsenic in Annaowan, characterized in that, Includes the following steps: S1 Raw Material Pretreatment: The 15 medicinal materials in the legal prescription of Annaowan are respectively cleaned, washed, dried, crushed and sterilized. Among them, cinnabar and realgar are processed by water-milling to obtain water-milled powder. S2 Total Mixing: The powders of six kinds of herbs and eight kinds of precious and fine herbs are mixed evenly using the equal-volume incremental dilution method to obtain the raw material powder for Annao Pills; S3 Preparation: The following steps are performed sequentially: honey refining, honey warming, mixing and fermentation, pill making, coating, packaging, wax sealing and transfer printing to obtain the finished product of Annao Pills; S4 full-process quality control includes three stages: raw material testing, intermediate product testing, and finished product testing. Raw material testing focuses on divalent mercury, trivalent arsenic, and pentavalent arsenic in cinnabar and realgar. Intermediate product testing covers all key processes. Finished product testing is carried out in accordance with legal quality standards for all items.

2. The whole-process quality control and preparation process of soluble mercury and arsenic in Annaowan according to claim 1, characterized in that, In step S1, the testing of the cinnabar raw material includes: appearance, identification, iron content inspection, determination of divalent mercury content, and determination of mercuric sulfide content, wherein the divalent mercury content, calculated as mercury, shall not exceed the legal limit, and the mercuric sulfide content shall not be less than the legal requirement; the testing of the realgar raw material includes: appearance, identification, determination of the total content of trivalent and pentavalent arsenic, and determination of arsenic disulfide content, wherein the total content of trivalent and pentavalent arsenic, calculated as arsenic, shall not exceed the legal limit, and the arsenic disulfide content shall not be less than the legal requirement.

3. The whole-process quality control and preparation process of soluble mercury and arsenic in Annaowan according to claim 1, characterized in that, In step S1, the cleaning process is carried out on a sorting workbench to remove impurities and non-medicinal parts from Scutellaria baicalensis, Coptis chinensis, Gardenia jasminoides, Curcuma longa, gypsum, and mother-of-pearl; the washing process uses a washing machine to wash the cleaned Scutellaria baicalensis, Coptis chinensis, Gardenia jasminoides, and Curcuma longa at room temperature by spraying with flowing water; the drying process uses a hot air circulating oven to dry for a specified time at a suitable temperature, and the thickness of the material in the drying tray does not exceed the specified value.

4. The whole-process quality control and preparation process of soluble mercury and arsenic in Annaowan according to claim 1, characterized in that, In step S1, the pulverizing process uses a hammer mill to pulverize pearl, calcined ochre, and borneol into fine powder, wherein the pearl and calcined ochre pass through a sieve of a specified mesh size, and the borneol passes through a sieve of a specified mesh size; a coarse crusher is used to mix and coarsely crush Scutellaria baicalensis, Coptis chinensis, Gardenia jasminoides, Curcuma longa, mother-of-pearl, and gypsum into coarse powder; and a micro-pulverizer is used to pulverize the above coarse powder into fine powder and pass it through a sieve of a specified mesh size.

5. The whole-process quality control and preparation process of soluble mercury and arsenic in Annaowan according to claim 1, characterized in that, In step S1, the sterilization process uses a multi-functional traditional Chinese medicine sterilization cabinet to sterilize the herbal powder and calcined hematite powder. The sterilization temperature, sterilization time, and drying time all meet the specified requirements, and the thickness of the spread material does not exceed the specified value.

6. The whole-process quality control and preparation process of soluble mercury and arsenic in Annaowan according to claim 1, characterized in that, In step S2, the equal-volume incremental dilution method specifically involves: ① mixing borneol powder with an equal amount of herbal powder and passing it through a sieve of a specified mesh size; mixing a portion of realgar powder with an equal amount of herbal powder; and then mixing the two mixtures together and passing them through a sieve of a specified mesh size; ② mixing the remaining realgar powder with a portion of the herbal powder; mixing calcined ochre powder with pearl powder; premixing artificial bezoar powder with an equal amount of cinnabar powder and then mixing it with the remaining cinnabar powder; and then mixing the three mixtures together and passing them through a sieve of a specified mesh size; ③ alternately adding ①, ②, and a portion of the herbal powder into a mixer and mixing for a specified time; ④ then alternately adding pig bile powder, buffalo horn concentrate powder, and the remaining herbal powder into a mixer and mixing for a specified time.

7. The whole-process quality control and preparation process of soluble mercury and arsenic in Annaowan according to claim 1, characterized in that, In step S3, the honey refining process refines the honey at a specified temperature, and the relative density is controlled within a specified range; the honey warming process heats the refined honey to a specified temperature; the mixing and resting process mixes the Annaowan raw material powder, menthol, and warm honey in a specified ratio and stirs for a specified time to form a soft material, which is then rested at room temperature for a specified time.

8. The whole-process quality control and preparation process of soluble mercury and arsenic in Annaowan according to claim 1, characterized in that, In step S3, the pill-making process uses a horizontal automatic pill-making machine to produce small honey pills of a specified weight. During the pill-making process, the weight difference of the pills is controlled within the warning limit and the correction limit. In the coating process, diluted honey and Annao pill raw material powder are alternately sprinkled on the pills to make the pills round and uniform in appearance and consistent in color.

9. The whole-process quality control and preparation process of soluble mercury and arsenic in Annaowan according to claim 1, characterized in that, In step S4, the intermediate product testing includes: degree of cleanliness, degree of washing, degree of drying, fineness of grinding, sterilization effect, uniformity of mixing, quality of soft material, weight difference of pellets, appearance of coating, quality of packaging, quality of wax sealing, and quality of pad printing; the finished product testing includes: properties, identification, arsenic trioxide test, weight difference, dispersibility time, moisture content, content determination, and microbial limits, wherein the arsenic trioxide test meets the legal requirements, and each 1g of finished product contains no less than the legal limit for borneol and menthol.

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