Technical guidance for processing research of new medicinal pieces of traditional Chinese MedicinePrinciple (Trial)

1、 Overview

The processing of new medicinal pieces of traditional Chinese medicine is closely related to the quality control and clinical efficacy of new drug preparations. It is necessary to follow the theory of traditional Chinese medicine in the development stage of new drugs, and carry out research around the characteristics of new drugs and research design needs. This guiding principle is formulated to guide the processing research of new medicinal pieces of traditional Chinese medicine and provide safe, effective and stable quality pieces for the production of traditional Chinese medicine preparations.

This guiding principle mainly includes processing technology, processing excipients, decoction pieces standards, packaging and storage, etc., aiming to provide references for the research of the processing of new medicinal decoction pieces of traditional Chinese medicine.

2、

（1） Follow the theory of traditional Chinese Medicine

The processing research of decoction pieces should follow the theory of traditional Chinese medicine, inherit the traditional processing experience and technology, and maintain integrity and innovation. The processing method, process parameters, processing degree, storage conditions and maintenance management of decoction pieces should respect the traditional processing experience and technology. It is encouraged to carry out research on the processing of decoction pieces by combining traditional experience with modern science and technology.

（2）

The processing research of decoction pieces should meet the needs of the research and design of new drugs of traditional Chinese medicine, and the processing parameters and quality requirements should be determined according to the key quality attributes of medicinal materials, production equipment capacity and other research. If it is necessary to adopt other processing methods for new medicinal pieces of traditional Chinese medicine, sufficient research should be carried out. The specifications of new medicinal pieces of traditional Chinese medicine and those for clinical dispensing can be different. On the basis of following the traditional processing methods, the appropriate specifications and quality requirements of the pieces should be determined according to the characteristics of the medicinal materials and the production scale of the preparation, the characteristics of the extraction process, and the quality control requirements. .

（3） Establish and improve quality standards

According to the needs of the research and design of new drugs of traditional Chinese medicine and the research results of the correlation of the quality standards of medicinal materials, decoction pieces and traditional Chinese medicine preparations, the corresponding decoction piece standards should be established and improved, and the establishment of its detection items should pay attention to the correlation with safety and effectiveness. The medicinal materials and excipients for processing should meet the relevant standards. For non-standard decoction pieces and processing excipients, corresponding standards should be established. .

（4） Strengthen the whole process quality control

. We should encourage the use of modern information technology to establish a traceability system for decoction pieces, so that the source can be checked and the destination can be traced.

3、

（1） Processing technology

According to the theory of traditional Chinese medicine, clinical medication and the research and design needs of new drugs of traditional Chinese medicine, on the basis of inheriting the traditional process, the specific processing technology research of purification, cutting, processing and other processing of medicinal materials was carried out, and the process parameters, production equipment, etc. were determined, and the process validation was carried out. The production equipment used for processing should be compatible with the processing technology, production scale and quality requirements of decoction pieces.

1Net system

The commonly used methods include selection, air separation, water separation, screening, cutting, scraping, chipping, removing, brushing, wiping, grinding, collision, etc. .

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2. cutting

Except for a few fresh cut and dry cut medicinal materials, they generally need to be softened to make the medicinal materials easier to cut. The commonly used softening methods include spraying, elutriation, soaking, bleaching, moistening, etc. the appropriate softening method should be studied and selected to avoid the loss or damage of effective ingredients, and the specific softening method, equipment, water absorption, temperature, time and other process parameters should be clarified.

. If the varieties cut fresh in the place of origin are not included in the national drug standards or the standards or processing specifications of medicinal materials (decoction pieces) of provinces, autonomous regions, and municipalities directly under the central government, they should be fully compared with the traditional methods. If the medicinal materials are processed into pieces suitable for extraction by crushing and other technologies, the rationality of the method should be studied and explained, and appropriate methods and parameters should be selected according to the characteristics of the medicinal materials, so that the size of the broken pieces is distributed in a suitable range.

3. roasting

Commonly used methods include stir frying, roasting, calcining, steaming, boiling, copying, simmering, etc. The influence of temperature, time, type and dosage of auxiliary materials used on the quality of decoction pieces should be fully considered in processing, and the key processing parameters of processing should be studied and determined in combination with the characteristics and specifications, production equipment and scale of decoction pieces. In case of frying, the frying equipment (such as model, working principle and key technical parameters), specification of decoction pieces, feeding amount, frying temperature (the test point of frying temperature should be specified in combination with the equipment situation), speed, frying time and other process parameters should be clarified. If it is necessary to add auxiliary materials, the type, dosage and adding method of auxiliary materials shall be specified. . 

For special processing methods such as fermentation method, germination method, water flying method and frost making method, the traditional processing technology should be fully respected, and the key process parameters and production equipment should be clarified.

4. drying

The pieces that need to be dried during processing should be treated in time to avoid microbial contamination, deterioration, corruption, etc. due to untimely drying. Common drying methods include sun drying, shade drying, drying, etc. Appropriate drying methods and conditions should be selected according to the specific properties of decoction pieces, and the drying equipment, temperature, time, material thickness, etc. should be studied to clarify the methods and process parameters. In the drying process, effective measures should be taken to prevent the pieces from being contaminated and cross contaminated, and new low-temperature drying technology should be encouraged.

（2） Processing excipients

1. preparation of processing excipients

If the processing auxiliary materials need to be purchased, the products prepared by traditional process should be generally selected. For example, vinegar should be brewed from rice, wheat, sorghum, etc., without adding colorants, flavoring agents, etc。

If the processing excipients need to be prepared by yourself, they should generally be prepared according to the processing specifications of decoction pieces and medicinal materials/For the preparation method of standard loading of decoction pieces, strengthen the process control to ensure the quality stability of processing excipients. If necessary, the preparation method should be studied to clarify the preparation method and process parameters. .

The preparation method of excipients is not included in the national drug standards or the medicinal materials of provinces, autonomous regions and municipalities directly under the central government/.

For animal derived excipients, inactivation research and verification of pathogenic microorganisms that may cause zoonoses should be carried out.

2. standards for processing excipients

If the processing excipients have medical or edible standards, the original standards can generally be used, and they can be improved according to traditional experience and processing requirements when necessary. If there is no standard, it should be combined with its quality characteristics to study and establish a quality standard that meets the requirements of pharmaceutical use.

For auxiliary materials from special sources, targeted research should be strengthened. If the excipients are from minerals, heavy metals and harmful elements should be studied, and corresponding detection items should be established in the excipient standards when necessary; For animal derived excipients, pathogenic microorganisms that may cause zoonoses should be studied, and corresponding detection methods should be established when necessary.

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3Packaging and storage of processing excipients

Appropriate packaging materials shall be selected according to the characteristics of auxiliary materials/If necessary, the compatibility study of auxiliary materials and packaging materials shall be carried out. The storage conditions of processing excipients were determined according to the stability study results.

（3） Standard for decoction pieces

. The establishment of reasonable standards for decoction pieces and the quality control of the whole process of the processing of decoction pieces are conducive to ensuring the stability of the quality of decoction pieces. Processed by special methods or having“Different treatment of raw and cooked food”The characteristic decoction pieces should establish the exclusive property control method that is different from the corresponding raw products.

Generally, the content of the standard for decoction pieces includes: name, origin, origin, processing, character, identification, inspection, extract, content determination, nature, taste and meridian, function and indications, usage and dosage, attention, storage, etc. In addition, it is encouraged to strengthen research on the characteristics of decoction pieces and common problems such as dyeing, weight gain, adulteration, and easy mildew and deterioration. According to the needs of risk management, according to the relevant national supplementary test methods or research to add targeted test items, establish corresponding test methods, and include them in the standards when necessary.

The following is a brief description of the main research contents and general requirements of some items in the decoction pieces standard:

[processing] specify the processing method, key process parameters, types and dosage of excipients, and requirements for processing degree of decoction pieces.

[properties] describe the shape, size, color, taste, smell, texture, etc. according to the characteristics of the decoction pieces used in actual production; .

[identification] traditional empirical methods, microscopic identification methods, chemical reaction methods, chromatography, spectroscopy and other methods are used to establish the specificity identification methods of decoction pieces, especially the decoction pieces with fake and easily confused products. Sufficient comparative research should be carried out to explain their specificity. In the research process of identification methods, it is encouraged to use reference medicinal materials (decoction pieces), reference extracts, standard atlas, etc. as controls to improve the specificity of identification methods. In order to improve the specificity of TLC identification methods, the description of the number, color, location and other contents of identification spots should be improved according to the research results.

[inspection] the water content, total ash, acid insoluble ash, sulfur dioxide residue and other items in the decoction pieces shall be studied, listed in the standards when necessary, and reasonable limits shall be formulated. For the safety inspection items such as heavy metals and harmful elements, pesticide residues, mycotoxins, etc., it should be combined with the research on the source of medicinal materials, production and processing process, and included in the standards when necessary. For toxic decoction pieces or decoction pieces recognized as toxic by modern research, the limit inspection items of toxic ingredients should be established in the standard. If the decoction pieces are directly crushed and used as medicine, the microbial inspection item should be added to the quality standard according to the process of traditional Chinese medicine preparation. Targeted inspection items should be established according to the characteristics of animal, mineral, fermentation, resin and other decoction pieces.

[extract] the appropriate solvent should be selected to establish the detection method of the extract according to the factors such as the ingredients in the decoction pieces and the extraction process of traditional Chinese medicine preparations, and the correlation with the medicinal materials and traditional Chinese medicine preparations should be investigated to establish a reasonable limit.

[content determination] according to the quality characteristics of decoction pieces and traditional Chinese medicine preparations, research and establish the content determination methods of effective ingredients, index ingredients or major components related to safety and effectiveness, investigate the correlation with traditional Chinese medicine and traditional Chinese medicine preparations, and specify reasonable content limits. If the decoction pieces are both toxic and effective ingredients, the content determination method should be established and a reasonable content limit should be specified.

If the quality control items established in the quality standard of traditional Chinese medicine preparations are related to the quality of decoction pieces, the corresponding quality control items should be established in the decoction pieces standard, and the reasonable quality requirements should be determined according to the research results.

（4） Packaging and storage

The packaging and storage of decoction pieces should be convenient for storage and use. According to the characteristics of decoction pieces, combined with the actual production and processing experience, determine the appropriate packaging materials (containers) and storage conditions. 

1. packaging

Appropriate packaging materials (containers) and packaging specifications should be selected according to the characteristics, storage and use requirements of decoction pieces and in combination with actual production experience. The packaging of decoction pieces shall not affect the quality of decoction pieces, and shall be convenient for storage, transportation and use. Packaging materials and containers in direct contact with decoction pieces shall meet the national quality standards for drug and food packaging. Pay attention to the packaging of special decoction pieces that are easy to volatilize, pollute, damp and deteriorate. There shall be obvious package marks on the package of decoction pieces, which shall comply with the relevant national regulations.

2. storage

According to the traditional experience and the characteristics of decoction pieces, the appropriate storage conditions and maintenance technology were determined according to the stability inspection results of decoction pieces. Necessary maintenance and management shall be carried out during storage. If insect and moth proofing treatments are required, the methods and parameters used shall be studied. The maintenance treatment shall not affect the quality of decoction pieces, and detailed records shall be made.

4、 Main references

1. State Food and drug administration. Guiding principles for pretreatment technology of raw materials of traditional Chinese medicine and natural medicine2005year.

2. Ministry of health. Good manufacturing practice（2010Revised in)2011Years