Considerations on the Quality Standards Reflecting the Characteristics of Compound Preparations of Traditional Chinese Medicine

Zhao Wei,Wu Zhi’ang

(School of Business Administration,Shenyang Pharmaceutical University,Shenyang 110016,China)

Abstract Objective To study the current quality standard of traditional Chinese medicine (TCM) and its limitations in China,and encourage enterprises to take more responsibility to promote the development of this industry.Methods Based on the analysis of the status quo and problems of the quality standard system of TCM,the quality control mode,as well as the problems found in the reevaluation after marketing,some suggestions were put forward for adjusting the current quality standard of TCM.Results and Conclusion Through strengthening the quality control of the source,and under the premise of ensuring the safety,effectiveness and stability of TCM,the quality standards of TCM can be improved greatly.

Keywords: Chinese medicine compound;quality standard;quality control

In 2019,the Central Committee of the Communist Party of China and the State Council promulgated the “Opinions on Promoting the Inheritance,Innovation and Development of Traditional Chinese Medicine”,encouraging technological innovation to promote the quality of traditional Chinese medicine (TCM) as well as the development of the TCM industry.TCM s are mostly compound medicines,which are composed of multiple medicinal herbs with several ingredients.Various chemical reactions will occur during the mixing and preparation of multiple medicinal materials,and new ingredients will be produced.Due to the complexity of components,it is more difficult to control the quality of compound preparations in TCM than chemical drugs with single structural component.In addition,Chinese medicinal materials are derived from natural animals and plants,which have complex biological characteristics.Besides,the production chain of TCM is long.From the cultivation of medicinal materials,harvesting,processing of decoction pieces,to preparation production,many links can have an impact on the quality of the medicine.The highquality production of TCM requires the same level of research on quality standards.However,the current quality control mode of TCM does not match the industrial production,which cannot fully reflect the characteristics of TCM.This article discusses the existing problems in the quality control mode of TCM and puts forward some suggestions for the highquality development of the TCM industry.

1 Current status of quality standard system and quality control mode of TCM

The TCM standard system includes national drug standards (“such as the Chinese Pharmacopoeia I”,standards issued by the National Health Commission of the People’s Republic of China,standards issued by the National Medical Products Administration(NMPA),and supplementary inspection methods by the NMPA),registration standards,and local standards(such as local Chinese medicinal materials standards,preparation specifications of decoction pieces,and preparation regulations of medical institutions).The quality standards cover the entire chain of medicinal materials,decoction pieces,vegetable oils and extracts,and preparations.At the same time,in response to the quality problems found after marketing,the supplementary inspection method of TCM approved by the NMPA also provides strong regulatory support.So far,there have been more than 200 approvals for supplementary inspection methods involving TCMs,including inspection items for illegal dyeing,adulteration,and violations of the production process of proprietary Chinese medicines in medicinal materials[1-3].

TCM quality control mainly relies on the authenticity of medicinal materials,the empirical nature of the preparation process,and the ethical constraints of the traditional medicine industry.The quality standards are completely based on experience to identify the appearance and shape of medicinal materials,without quantitative indicators.Therefore,it lacks specific identification items,which results in the limitations of strong subjectivity and poor operability[4].With the development of the TCM industry and the promotion of science and technology,the quality standards of TCMs are continuously improved and perfected.The standard content includes name,prescription,preparation method,properties,identification,inspection,content determination,function and indication,usage and dosage,specifications,and conditions for storage,etc.Compared with the quality standards of chemical drugs,TCM standards have obvious characteristics of preparation method,function and indication,usage and dosage,which reflect the process control of TCM.The current quality control mode of Chinese medicine compound preparation is basically based on the quality control mode of chemical drugs.It means two index components or active ingredients are used to determine whether the drug is qualified through qualitative and/or quantitative analysis[5].

2 Existing problems

2.1 Limitations of quality standards for TCMs

Due to the increasingly scarce resources of Chinese medicinal materials and rising prices,adulteration is common in the market.At present,most of the quality control indicators of Chinese medicinal materials are only a single measurable component or index component,which cannot determine the authenticity of the source medicinal materials.So,the quality of some TCMs cannot be guaranteed.Inspection items and methods cannot effectively identify and monitor the quality of TCM.Many TCM standards were promulgated a long time ago,whose control methods of quality standards were relatively rough.For instance,chemical color reaction,precipitation reaction,ultraviolet colorimetry and other methods are used to determine the quality.However,these methods have the problem of low specificity,which cannot control the quality of medicines.There is much room for improving the quality of TCM.

Chinese medicine compound preparations have many complex ingredients,but the quality standards cannot fully reflect the product quality and efficacy.TCM is different from chemical drugs,because its material basis is not a single component or several components,but multiple components and multiple targets play a role together.So,it is not the higher the content of these two ingredients,the better the quality of the medicine will be.This quality control mode that only relies on one or two components is not suitable for complex Chinese medicines since it cannot reflect the overall quality of TCM.Therefore,its limitations gradually become obvious.With the development of multi-component determination methods,such as fingerprinting,one test and multiple evaluation,and control extracts,the integrity of the quality standards of TCM is gradually improved.

In addition,due to some historical reasons,the standard update has not formed an effective mechanism.Some old methods that are not suitable for industrial production,or detection methods that are not combined with advanced technology,have not been eliminated in time,resulting in an increase in the number of standards,but a decline in the availability of these standards.There are multiple standards with the same name but different prescription quantities and different preparation methods.Therefore,when we encourage the industrialization of TCM,we need to establish a quality standard system that is compatible with it.At present,there is still much room for improvement in the quality standard system[6].

2.2 Problems found in re-evaluation after listing

Since 2008,Chinese government has adopted a combination of standard inspection and exploratory research to carry out evaluative sampling tests on post-marketing drugs,with the purpose of discovering potential drug quality problems through in-depth analysis and promoting the improvement of drug quality.For a long time,the drug regulatory authorities have attached great importance to the adulteration of Chinese medicinal materials and decoction pieces.However,at this stage,these quality standards can neither identify the authenticity of the medicinal materials,nor identify the quality of the medicines.The standards have many limitations.Through exploratory research,it has been found that for closely related varieties,such as preparations containing rhubarb,some preparations with Tibetan rhubarb,Hetao rhubarb,North China rhubarb,and Tianshan rhubarb are often confused with genuine rhubarb.The study found that these fake rhubarbs all contain rhubarb glycosides,and the inspection of rhubarb glycosides in the preparations can be used to identify the genuine rhubarb.In a similar situation,lonicera japonica is used to replace honeysuckle and we can establish lonicera saponins B to identify the fake one.Besides,adulterated tiger palm southern stars in pinellia ternata can be identified through establishing oliphiopogonis acid.Saikosaponin K can be used to identify if Tibetan bupleurum replaces bupleurum in TCM.In addition,cowhide and horse skin are used instead of donkey skin,and pig skin and donkey skin are used to replace tortoise shell glue and antler glue.The inspection methods of cowhide ingredients,donkey-skin ingredients,pigskin ingredients,horseskin ingredients,and characteristic peptides are used to identify the authenticity of the materials.Another example is using ginsenoside F11,a characteristic component of American ginseng,to distinguish the real ginseng from American ginseng in Chinese medicine.

For the use of non-medicinal parts,panax notoginseng is a good example.The pharmacopoeia stipulates that the medicine parts of panax notoginseng are roots and rhizomes,but panax notoginseng stems and leaves are often used as medicine.Studies have found that the content of ginsenoside Rb3 in the stems and leaves of panax notoginseng is relatively high,but there is almost no in the roots and rhizomes.Therefore,these specific components are generally used to distinguish fake products from genuine products.They can provide guarantees for the safe and effective clinical use of TCMs,which will also improve the quality standards of TCM.During the drug sampling,it was also found that some TCMs that did not specify the inspection items in the quality standards lacked some original materials,and some TCMs that did not specify the content determination items had not enough original materials[7-9].

3 Thoughts and suggestions

3.1 Attaching importance to the quality of the original materials and strengthening the research of methods with good identification

The identification of TCM quality standards generally use thin-layer chromatography for medicinal materials.Meanwhile,reference medicinal materials and/or reference substances are also used for identification.However,there are no specific identification methods to match the biodiversity of Chinese medicinal materials,which is particularly obvious in Chinese medicinal compound preparations.A single reference substance cannot effectively and comprehensively reflect the quality of medicines.Besides,the production of the single reference substance requires a large amount of raw materials,which will increase the production cost and waste the resources of Chinese medicinal materials.

The formulation of quality standards for TCMs can draw lessons from research results such as reevaluation.So,the way of formulating the current quality standards for TCMs should be adjusted,and the source control of medicinal materials must be focused on.It is necessary to add good specificity and high recognition items to the quality standards of decoction pieces,which can distinguish between authenticity and counterfeit.The testing items can ensure the quality of Chinese medicines from the source,and play a key control role in quality standards.

3.2 Reflecting the integrity of the quality of TCM

TCM compound preparations have various components with low content.One component generally accounts for a few percent,a few thousandths,or even a few ten thousandths of the weight of the preparation.The one or two index components selected by the quality standard cannot represent the quality of the product.Under the premise of continuous improvement of TCM detection and analysis methods,it is necessary to use methods suitable for prescriptions and process characteristics to reflect the integrity of quality.For instance,we can change the detection wavelength to measure multiple components.In addition,reference extracts,and feature maps or fingerprint can also be used[10,11].The content determination of preparations should have a range instead of just setting a low content limit.It is not conducive to the stability control of the quality of Chinese medicines,which may also give opportunities for adulteration or fake products.The development of quality standards for TCMs pays more attention to integrity and consistency,which requires manufacturers to focus on the quality of raw materials,the standardization of production processes,and the stability of TCMs.

3.3 The correlation between quality and efficacy

Due to weak basic research,the index components selected in the quality standards of TCMs are not closely related to the effectiveness and safety of these medicines.Besides,the quality standards cannot fully reflect the efficacy of the products.On the other hand,the curative effect of TCM does not have a simple linear relationship with the content of ingredients,that is,the higher the purity,the better the quality.The quality standards of TCMs should not just rely on the specified quality,but to reflect the effectiveness and safety of the products.Through in-depth nonclinical research and clinical trials,we can find quality markers to establish associations.For some varieties,when the conditions are mature,the quality control mode combined with the physical and chemical analysis of the main components and the biological activity determination method can be used.Besides,the quality control mode of the spectrodynamics of TCM can also be tried.This comprehensive quality control mode can ensure the safety,effectiveness and quality of TCMs[12,13].

3.4 Strengthening the quality control of the whole process

There are many factors that affect the quality of TCMs.In order to ensure the stability and controllability of TCM in industrial production,it is necessary to comprehensively use some methods to improve the quality,which is also the whole process control idea.In the research of new TCM compound preparations,it is generally recommended to use stable quality medicinal materials through fixed base and collection period.For preparations with multiple process routes,each process route shall have quality control indicators to guarantee the stable process.For solid preparations made by extraction,purification,and concentration,according to the characteristics of the prescription and process,the extract inspection items should be established to control the amount of extract.These quality control methods play an important role,and they are related to the effectiveness and stability of TCM.For toxic medicinal materials,the traditional processing technology has a detoxification effect,and its processing method and quality control are particularly important[14].

4 Conclusion

The formulation of quality standards for TCM should be based on science,practicality,and simplicity.Following the holistic view of TCM theory and combining traditional sensory recognition can be combined with modern detection technology to improve the accuracy of detection.Through the use of new technologies,enterprises can improve the quality of raw materials,production,packaging and storage of medicines.Meanwhile,the detection standard system should be integrated into the process to establish and improve the integrity and specific characteristics of TCM,which not only ensure the safety and effectiveness,but also increase efficiency and reduce costs of industrial production of TCMs.