A practical roadmap for upgrading clinically used formulas into modern, evidence-driven botanical products

Abstract

Further study and secondary development of clinically applied Traditional Chinese Medicine (TCM) is an important pathway for the research and development (R&D) of new TCM products. In 2023, China's National Medical Products Administration (NMPA) issued the Special Regulations on Registration Management of Traditional Chinese Medicine, which refined R&D requirements for new TCM and supported the development of new TCM rooted in extensive clinical practice-highlighting clear opportunities for the secondary development of strong, well-established varieties.

This article proposes a re-innovation R&D strategy for TCM based on re-evaluation and rediscovery, aligned with the inherent characteristics and scientific principles of TCM. Through systematic research into the effectiveness and safety of real-world clinical applications-especially for clinically high-risk preparations, injections, large-market ("big brand") TCM products, and widely used clinical prescriptions-the strategy aims to improve the quality and safety of TCM preparations and provide references for improvement research and secondary development. On this basis, the further discovery of superior substance components can become an engine for innovative TCM and promote the high-quality development of modernized TCM.

Key words: re-evaluation, rediscovery and re-innovation; secondary development of traditional Chinese medicine; components of traditional Chinese medicine; improved new traditional Chinese medicine; R&D strategy

 

1. Why "re-innovation" matters now (and why it's relevant to EU/US botanical developers)

TCM is a major healthcare, economic, scientific, cultural, and ecological resource in China, and its inheritance and development have long been prioritized at the national level. Since the implementation of the Drug Administration Law of the People's Republic of China in 1985, China's drug regulatory authorities have continuously strengthened quality control and safety supervision for TCM, and have promoted the approval of innovative TCM products with good efficacy and controllable quality-making significant contributions to high-quality development of TCM preparations.

On February 10, 2023, the NMPA officially issued the Special Regulations on Registration Management of Traditional Chinese Medicine [1], further detailing requirements for new TCM R&D and registration. The regulations support the development of new TCM based on ancient classical formulas, experience formulas from renowned senior TCM practitioners, and medical-institution preparations, and encourage post-marketing studies and secondary development of already marketed TCM products.

China currently has more than 58,000 TCM approval numbers [2]. Many are legacy approvals, and multiple approvals may exist for the same underlying product. Due to historical factors, early-approved TCM products often had relatively weak basic research foundations and lacked high-level scientific evidence demonstrating clinical value. As a result, many products face challenges such as unclear pharmacodynamic substances and mechanisms of action, rough production processes, and low-level quality control technologies. Market homogeneity has also created a "bad money drives out good" dynamic, intensifying destructive competition.

Regarding new TCM applications, from 2020 to 2023, the Center for Drug Evaluation (CDE) approved 144 TCM products for clinical trials and 28 for marketing authorization (see Fig. 1) [3]. The data suggest that since 2020, clinical approvals have increased substantially, while the total number of marketed approvals has not changed dramatically. A plausible reason is that China raised technical R&D requirements and review standards for new TCM, significantly reducing repetitive, low-level submissions and increasing the approval threshold [4]. This indirectly reflects insufficient innovation depth in TCM R&D, which to some extent constrains modernization.

Implication for Western botanical developers (including Cistanche/Rou Cong Rong supply chains):
If you want serious differentiation-clinically credible claims, consistent batches, defensible quality, better safety-then "re-innovation" is a realistic, scalable path: build on existing human-use experience, then upgrade the evidence, chemistry, and manufacturing.

2. Scientific meaning of "Re-evaluation → Rediscovery → Re-innovation"

The "re-evaluation–rediscovery–re-innovation" model should reflect TCM's multi-component, multi-link, multi-target holistic action. It calls for applying advanced technologies and systematically researching TCM with:

Re-evaluation as the foundation

Rediscovery as the key

Re-innovation as the ultimate goal

Re-evaluation tracks and assesses effectiveness, safety, and real-world use, enriching evidence beyond pre-market studies, and supplementing research on clinical positioning, efficacy mechanisms, and quality standards. After more than a decade of development, post-marketing re-evaluation has improved overall TCM quality and clinical medication safety [5] and is now an important part of drug evaluation.

Currently, re-evaluation focuses mainly on safety, effectiveness, and pharmacoeconomics-especially safety of TCM injections (e.g., post-marketing re-evaluation of Danshen Injection) [6]. However, mechanisms are still incomplete: many studies do not deeply address key issues found during re-evaluation, such as safety/effectiveness concerns, vague indications, and controllability across batches. These are essentially rooted in insufficient preclinical research depth. Therefore, it is crucial to use modern science to interpret the "scientific connotation" of marketed TCM; discover superior efficacy components from re-evaluation; optimize clinical functions/indications; and implement re-innovation to drive higher-quality new product development.

Core logic (see Fig. 2):
Conduct comprehensive re-evaluation across clinical use, pharmacology, chemical substances, and formulation/process. Precisely position indications and clarify mechanisms, then rediscover clinical value and "component-structure" features.

TCM efficacy is not a simple sum of herbs nor subtraction of toxicity. Components interact synergistically. Its active material basis includes effective components (directly responsible for efficacy) and functional components (do not directly produce efficacy but may enhance solubility, reduce toxicity, or amplify effect) [7]. Systematic multi-component efficacy research-using modern pharmacology and bioinformatics-helps clarify active components, core targets, mechanisms, formulation features, and compatibility rules to power re-innovation.

At the same time, optimize at multiple dimensions and levels: starting from medicinal materials, processing, decoction pieces, and component-structure characteristics. Use modern formulation technologies to improve extraction/separation, refining/purification, and pre-processing, and design dosage forms based on properties and clinical use to achieve breakthroughs in quality standards, mechanisms, and manufacturing-ultimately improving internal quality.

3. Development strategy based on re-evaluation, rediscovery, and re-innovation

3.1 Research strategy during re-evaluation

Re-evaluation is the starting point: it systematically assesses how TCM is used under real conditions. A robust re-evaluation system can extend into re-innovation, improving product performance.

Re-evaluation should be guided by precise clinical positioning, and should incorporate pharmacology, chemical composition, and manufacturing/process research aligned with compound-formula characteristics. This supplements high-quality clinical evidence on effectiveness and safety and clarifies post-marketing issues. After accurately defining clinical use boundaries, pharmacology can deepen understanding of efficacy and main indications, supporting investigation of new indications. Chemical and process research can reveal interaction patterns between components and support selection of stable, controllable processes and optimized component structures. (See Fig. 3.)

3.1.1 Re-evaluation based on clinical application

Historically, TCM clinical studies often had short durations, small sample sizes, and vague positioning, resulting in overly broad indications and unclear advantages-hindering precise use and increasing risk of inappropriate application and toxic events. The "Sho-saiko-to (Xiao Chai Hu Tang) incident" in Japan is a notable example; a key cause was detachment from TCM theoretical guidance and unclear clinical positioning [8]. Therefore, re-assessing a product's distinctive advantages versus comparable therapies and clarifying clinical positioning is a prerequisite.

To precisely position clinical use, one should combine expert experience with comprehensive analysis of literature and clinical data; collect real-world reports on use, adverse reactions, and basic research; integrate human-use experience with real-world evidence; initially define indication scope and dosing; and apply systematic review/meta-analysis to evaluate efficacy and safety across different syndromes/diseases.

For products with insufficient evidence, evidence-based evaluation should be emphasized. Data from randomized controlled trials can be combined with pharmacokinetics and preclinical pharmacology to identify patterns and define clinical advantages. For example, Qizhi Tongluo Capsules, with actions of activating blood, tonifying qi, and dredging collaterals, were studied using multi-omics network analysis and evidence-based methods based on formula target-spectrum efficacy relationships; the results suggested clear advantages over similar products in improving lower-limb motor function [9].

Safety re-evaluation is equally crucial. Real-world data (retrospective analyses, case reports, safety monitoring, adverse event reports) can characterize adverse reactions and identify relevant components and risk factors-particularly important for injections. Hospital-based intensive monitoring studies have been conducted for higher-risk injections with stronger prior foundations, such as Reduning Injection [10] and Shenfu Injection [11], to quantify adverse reaction rates and key influencing factors and provide evidence for safety.

Human-use experience is valuable but often suffers from weak data infrastructure and confounding in real-world settings (individual variability, inconsistent evaluation standards, variable data quality). It may remain at "experience summary" level and not translate into R&D [12]. To address this, under standardized methods for organizing famous practitioner experience, patient-centered R&D approaches, patient-reported outcomes, and other methods that reflect TCM characteristics should be used, while controlling data quality throughout the R&D process [13].

3.1.2 Re-evaluation based on pharmacological action

TCM acts through multiple components, targets, and pathways. Its complexity and historic limitations can prevent systematic elucidation of mechanisms, and nonclinical safety datasets may be incomplete. For classical formulas, traditional texts may be incomplete or non-standardized and cannot fully describe etiology/pathogenesis and syndrome indications [14]. Therefore, modern TCM research tools should be used to re-interpret functions and accurately define pharmacological actions. High-value products need deeper pharmacology/toxicology re-evaluation to clarify scientific meaning.

Pharmacological research should be based on re-evaluated clinical positioning and prior foundations, select internationally recognized models that reflect disease features, and choose representative efficacy endpoints while considering TCM syndrome characteristics-ensuring objectivity and clinical relevance and supporting new indication discovery [15]. With rapid development of big-data mining, bioinformatics, and multi-omics, system biology approaches have become key. Li et al. explored multi-target integrative regulation mechanisms and proposed "network target" theory, establishing key network pharmacology methodologies for mechanism elucidation, active substance discovery, and quality marker mining-especially for compound formulas [16].

For nonclinical safety evaluation, toxicology should predict potential adverse reactions. Screening should focus on allergy/pseudo-allergy, hepatic and renal toxicity, etc., identify adverse-reaction-prone components, analyze mechanisms and metabolism, and establish limits for toxic components [17]. For example, Longdan Xiegan Pill historically contained Guan Mutong; aristolochic acid from this source can cause strong nephrotoxicity. Replacing with Mutong avoided detectable aristolochic acid while preserving efficacy, meeting safe-use needs [18].

3.1.3 Re-evaluation based on chemical composition

Chemical constituents are the material basis of efficacy. Identifying the active material basis supports improved extraction/refining and dosage-form design, and enables modern quality-control models. Traditional research often focused on marker components from single herbs (especially main herbs) [19]. With modern analytics, HPLC and LC–MS are widely used to characterize composition systematically.

Once representative compounds are identified, pharmacological action can guide identification of truly effective substances. Historically, natural-product chemistry approaches extracted, separated, identified, and then screened for bioactivity to identify active components [20]. This approach discovered artemisinin and huperzine A. However, for multi-component formulas, using only one or a few activity endpoints cannot represent the full active material basis. Therefore, approaches such as molecular imprinting, bioaffinity chromatography, computer-aided virtual methods, component knock-out/knock-in, and equivalent component group discovery should be combined to identify efficacy groups more comprehensively [21]. Knock-out/knock-in studies in Coptis (Huanglian) [22] and Calculus bovis (Niuhuang) [23] have identified key efficacy components and "dose–effect" relationships, supporting innovation in component-based TCM.

3.1.4 Re-evaluation based on formulation/process technology

Manufacturing processes strongly influence chemical composition and thus efficacy. Even with identical prescriptions, different dosage forms may use very different processes, yielding different component profiles. Component levels and their ratios are crucial for efficacy [24]; therefore, products with different material bases and dosage forms should not necessarily share identical indications. Yet in the market, many products with the same prescription but different dosage forms/processes claim identical functions (e.g., Shuanghuanglian series [25], Yuanhu Zhitong series [26]).

Traditional extraction processes (e.g., water extraction and ethanol precipitation) are rough and can create complex interactions (solubilization, precipitation), potentially affecting efficacy and increasing risk. Safety issues in TCM injections highlight that manufacturing is critical; oversimplified processes, irrational clinical use, and insufficient post-marketing tracking contribute to adverse reactions [27]. For example, in Shenmai Injection, high-temperature sterilization can degrade ginsenosides into less soluble secondary saponins, creating flocculent precipitates. Conventional methods add polysorbate 80 to solubilize, but it has safety concerns [28]. Since red ginseng polysaccharides are endogenous polysaccharides in the injection, using native polysaccharide solubilization technology can significantly increase solubility and reduce adverse reaction incidence [29].

Modern scientific tools can also reveal the scientific basis of traditional processes. For example, for Baihu Decoction, phase separation plus particle size measurement and TEM characterization confirmed the existence of nano-phase structures, supporting scientific interpretation [30]. However, the actual effects of decoction nanoparticles on active constituents and in vivo mechanisms still require further research.

3.2 Research strategy during rediscovery

Rediscovery is the core driver. Based on re-evaluation, apply high-throughput screening, systems biology, network pharmacology, etc., to identify potential efficacy component groups and optimize their structure-transforming "effective" into "superior efficacy," and providing momentum for re-innovation.

3.2.1 Rediscovery based on new indications

With the TCM concept of "different diseases treated with the same method," formulas may treat multiple diseases sharing similar pathogenesis patterns. In practice or re-evaluation, new indications may emerge beyond common labeling. Selecting advantageous products for secondary development-supported by scientific re-formulation/recombination studies-can unlock new clinical value. For example, Jingqianping Granules were originally used to soothe the liver, regulate qi, relieve distension and pain, and later showed efficacy for menopausal syndrome; clinical trials further clarified safety and efficacy [31].

Computational methods can also predict new indications: high-throughput screening, molecular docking, and computational approaches can suggest new targets [32]. Molecular docking and dynamics can model interactions between active compounds and targets. For complex formulas, network pharmacology can identify which components regulate pathological networks, discover new targets and mechanisms, and validate through pharmacology/toxicology. Studies have used network pharmacology to identify main organs affected by Gualou Xiebai Banxia Decoction, suggesting positioning for acute cardiac conditions and predicting pathological links using data mining plus prior knowledge [33]. Another "component–target–disease" network approach revealed core targets and biological process networks for Liuwei Dihuang Pill, providing evidence for potential indications [34].

3.2.2 Rediscovery based on "component-structure" characteristics

Efficacy is usually not a single compound, but synergistic multi-component action. Jia Xiaobin proposed component-based TCM: "components" as basic units, grouped by physicochemical/pharmacological properties, with defined composition and ratio structures. Our group proposed the "component-structure" theory [35]: TCM material basis is a multi-dimensional, multi-level network; component content and inter-component ratios are key determinants of efficacy. Therefore, new TCM research should define efficacy components and represent the whole through known component groups [36]. Clarifying component-structure features supports standardization, modernization, and internationalization, and supports pre-formulation biopharmaceutics and component-innovation R&D.

This theory has been applied to elucidate material bases of well-known medicines such as Epimedium (Yinyanghuo) [37] and Isatis root (Banlangen) [38], and to study uniqueness and superior efficacy of medicinal materials. Whether a formula or single herb, overall efficacy relies on component groups [39]. Exploring deeper relationships within and between groups, combined with repeated pharmacodynamic tests and active screening, can identify component structures with equivalent or superior efficacy versus the original-supporting rational simplification and optimization [40]. Network pharmacology can efficiently identify major active groups and analyze how structural changes perturb disease networks, ultimately optimizing component ratios for superior clinical effect.

3.2.3 Rediscovery based on mechanism of action

Systems biology and integrative pharmacology show disease progression often reflects imbalance in complex biological networks. Effective intervention requires uncovering "multi-component–multi-target–multi-pathway" networks and regulating them holistically [41]. Combined with transcriptomics, proteomics, metabolomics, and network modeling, predicted results can be validated and differential genes/metabolites identified-interpreting compatibility rules and efficacy-material compatibility relationships. This supports rediscovery of mechanisms and new indications.

A classic example is Academician Chen Zhu's team dissecting the mechanism of Realgar–Indigo naturalis formula (Fufang Huangdai Pian) for acute promyelocytic leukemia at organ–cell–molecular/gene levels [42–43].

Modern pharmacology increasingly integrates AI, omics databases, and data mining, energizing TCM redevelopment. Still, limitations exist: database bias, limited professionalism, and lack of in vivo disposition information can reduce precision. Network pharmacology often only provides preliminary optimization; it must be strengthened by in vitro/in vivo experiments and clinical studies.

 

3.3 Research strategy during re-innovation

Re-innovation is the ultimate goal and runs through the entire development chain. Based on re-evaluation and rediscovery, it requires clinical-oriented multi-level optimization across medicinal materials processing, pre-formulation material preparation, and final manufacturing-raising overall quality.

3.3.1 Multi-level optimization from medicinal material sources

China has vast medicinal resources and multi-origin usage is common. Different species and regions can have different active substance levels and ratios, affecting product quality and efficacy. Deep textual research and historical verification of materia medica origins are essential: clarify historical changes via classical texts [44–45], compare differences by origin and region, and select appropriate sources to ensure quality, safety, and consistency.

After selecting optimal sources, processing ("paozhi") is often necessary to meet clinical needs. Scientific paozhi improves activity and safety; innovation in processing supports industrial development. Because diverse methods can cause confusion, processing should be optimized based on classical records and pharmacopoeial principles, with concrete parameters defined to obtain high-quality processed pieces. These can be used directly or further processed into modern raw materials.

With advances in extraction, separation, and purification, raw materials have evolved from powders and extracts to single compounds, component groups, and effective compound clusters. The future trend is refined raw materials with clear composition, validated efficacy, and stable content. Component-structure optimization is central: analyze multi-level composition and ratio relationships; conduct pharmacodynamic evaluation; screen best structural ratios; and obtain superior-efficacy component-structure material bases [24]. For example, Lou Fengchang et al. developed ginkgolide injection with total ginkgolides content up to 90%, with strong market potential and clinical value for mild-to-moderate cerebral infarction [46].

3.3.2 Dosage-form design based on biopharmaceutic properties

Oral administration is most common for TCM; solubility and permeability govern absorption. The biopharmaceutics classification system (BCS) classifies drugs by solubility and intestinal permeability. Building such frameworks helps target bioavailability improvements and resolve dosage-form design challenges.

Given different component solubility/permeability, our group developed a preliminary component biopharmaceutics classification system [47], applying modern formulation technology to improve solubility or permeability and thus developability and bioavailability [48]. Because TCM formulas contain many active substances with different biopharmaceutic properties, dosage-form design should be based on component-structure: design release units according to component biopharmaceutic properties [49], and use technologies such as multiparticulate timed/targeted release [50] and pH-dependent gradient release [51] to implement programmed release and maximize efficacy. For example, a time-based multi-unit release system for Dachuanxiong Formula improved in vitro/in vivo release behavior, enabling faster onset and longer maintenance through optimized compatibility ratios [52].

Emerging formulation technologies provide stronger theoretical and technical support for new TCM R&D. In practice, route and dosage form should match specific efficacy substances and clinical objectives, and should also meet industrialization needs.

3.3.3 Optimization of pre-processing and manufacturing

Manufacturing is the key quality control stage. Reliable processes are needed to produce high-quality, high-efficacy preparations. First, analyze each herb's properties and component interactions; then design process routes consistent with indications and traditional use to ensure efficacy and controllable safety. Improved processes must demonstrate safety and effectiveness, raise product quality, and meet industrial-scale requirements.

Modern process optimization uses chemical profiling with data mining algorithms and design-of-experiment methodologies (orthogonal, response surface, uniform design). For products with unclear material bases, re-evaluation/rediscovery strategies can inform process optimization and quality control. For example, component-structure theory enabled multidimensional dynamic quality control for Danshen infusion preparations, improving quality and safety [53]. However, evaluation indices must be rational: focusing only on enrichment may also concentrate toxic components. Process design should incorporate both pharmacodynamic and toxicological endpoints.

4. Conclusions and outlook: how to turn "heritage" into modern competitive advantage

A re-innovation strategy built on re-evaluation and rediscovery is a major future direction for TCM innovation. Secondary development can systematically identify efficacy substance patterns, detect toxic substances, clarify in vivo disposition of major components, and elevate holistic quality control. With supportive national policies, more technologies and methods suited to classical formulas, clinical effective prescriptions, and secondary development are emerging. While adopting new technologies, the outcome must still demonstrate clinical value, with strong focus on safety, effectiveness, and patient adherence, and R&D depth tailored to product type and market need.

At present, TCM re-evaluation often focuses on clinical high-risk preparations and major products, evaluating effectiveness, safety, and quality control to support clinical safety and manufacturing quality. On this basis, integrating network pharmacology, transcriptomics, network pharmacophores, and other approaches can more systematically reveal active material bases, uncover potential active substances or superior component groups, optimize formulas, expand new indications, and power re-innovation.

Despite strong industry growth, limitations in innovation technology and low R&D investment remain key bottlenecks. For time-tested, reliable traditional medicines, secondary development can increase scientific content, sharpen clinical positioning, and improve formulation technology and product quality. Secondary development can also conserve resources, improve efficiency, and raise value-by improving quality, clarifying therapeutic effects, and reducing adverse reactions.

This paper reviews recent hotspots in secondary development, analyzes approval trends, summarizes methods, and proposes an actionable strategy: use re-evaluation to expose real problems and real value; use rediscovery to identify superior substances and optimized structures; use re-innovation to rebuild quality and product competitiveness-ultimately enabling high-quality modernization.

Conflict of interest: All authors declare no conflict of interest.

 

References 

[1] National Medical Products Administration. Announcement on Issuing the Special Regulations on Registration Management of Traditional Chinese Medicine (Announcement No. 20, 2023) [EB/OL]. (2023-02-10) [2024-06-28]. https://www.nmpa.gov.cn/xxgk/fgwj/xzhgfxwj/20230210173401120.html.
[2] National Medical Products Administration. Drug database [EB/OL]. [2024-06-28]. https://www.nmpa.gov.cn/datasearch/home-index.html?3jfdxVGGVXFo=1709980197301#category=yp.
[3] Center for Drug Evaluation, NMPA. Accepted varieties information database [EB/OL]. [2024-06-28]. https://www.cde.org.cn/main/xxgk/listpage/9f9c74c73e0f8f56a8bfbc646055026d.
[4] Wang T, Zhou G, Zhao B, et al. Strategy analysis of TCM new drug R&D [J]. China New Drugs Journal, 2017, 26(8): 865–871.
[5] Chen Y, Ling X, Li C, et al. Research ideas on post-marketing clinical re-evaluation of TCM [J]. China New Drugs Journal, 2021, 30(24): 2262–2267.
[6] National Medical Products Administration. Notice on safety re-evaluation of TCM injections [EB/OL]. (2009-07-16) [2024-06-28]. https://www.nmpa.gov.cn/xxgk/fgwj/gzwj/gzwjyp/20090716152101457.html.
[7] Yan H, Chen X, Zhang Z, et al. Discussion on TCM research model based on components and "component-structure" theory [J]. Chinese Traditional and Herbal Drugs, 2015, 46(8): 1103–1110.
[8] Zhang Y, Shi Z, Shi J, et al. Analysis of "Sho-saiko-to incident" and "ancient formulas for modern diseases may be incompatible" [J]. Journal of Traditional Chinese Medicine, 2021, 36(6): 1172–1175.
[9] Yu Y, Li B, Liu J, et al. Evidence-based and multi-omics network analysis for precise clinical positioning of Chinese patent medicines: Qizhi Tongluo Capsules [J]. Chinese Journal of Experimental Traditional Medical Formulae, 2024, 30(3): 98–104.
[10] Gao Q, Qin K, Wang Y. Association rule analysis of adverse reaction factors of Reduning Injection [J]. Drugs & Clinic, 2023, 38(4): 962–968.
[11] Ma Z. Clinical study on efficacy and safety of Shenfu Injection for septic shock (yang qi collapse syndrome) [D]. Beijing: Beijing University of Chinese Medicine, 2023.
[12] Zhang Y, Xu X, Li F, et al. Implications of real-world research for rational application of human-use experience in TCM new drug development in China [J]. China Food & Drug Administration Magazine, 2022, (4): 35–42.
[13] An N, Han L, Chen P. Thoughts on real-world research for TCM new drugs under the "three-combination" evidence system [J]. China New Drugs Journal, 2022, 31(14): 1359–1363.
[14] Li Y, Wu B, Gao M. Suggestions on R&D status of classical famous formula preparations [J]. Chinese Traditional Patent Medicine, 2024, 46(7): 2488–2492.
[15] Cheng X, Jia X, Feng L, et al. Secondary development ideas for major TCM varieties based on systems theory [J]. China Journal of Chinese Materia Medica, 2013, 38(24): 4369–4374.
[16] Li S, Zhang B. Traditional Chinese medicine network pharmacology: Theory, methodology and application [J]. Chinese Journal of Natural Medicines, 2013, 11(2): 110–120.
[17] Zeng J, Chen P, Dai Y, et al. Risk–benefit and safety evaluation of classical famous formula compound preparations [J]. Pharmacology and Clinics of Chinese Materia Medica, 2022, 38(1): 209–218.
[18] Liu Y, Han S, Feng Q, et al. Determination of aristolochic acid A and B in TCM by UPLC-ESI triple quadrupole MS [J]. Chinese Journal of Chromatography, 2011, 29(11): 1076–1081.
[19] Zhao Y, Wang C, Han Y, et al. Key issues and prospects in modernization research of TCM [J]. China Guide of Pharmacy, 2011, 9(4): 123–126.
[20] Tu P, Shi S, Jiang Y. Ideas and methods for research on material basis of TCM [J]. Chinese Traditional and Herbal Drugs, 2012, 43(2): 209–215.
[21] Li C, Lu M, Liao J, et al. Systematic screening and identification of chemical components in Qikui Granules based on UPLC-QTOF-MS/MS [J]. Journal of Nanjing University of Chinese Medicine, 2023, 39(1): 57–69.
[22] Li J. Identification of efficacy substances and quality control model of Huanglian based on component knock-out/knock-in [D]. Kunming: Kunming University of Science and Technology, 2013.
[23] Kong W. Preliminary study on efficacy substance identification and quality control model of Niuhuang based on component knock-out/knock-in [D]. Chengdu: Chengdu University of Traditional Chinese Medicine, 2011.
[24] Yang B, Feng L, Jia X. Quality evaluation strategy for TCM preparations based on "component-structure" characteristics [J]. Chinese Traditional and Herbal Drugs, 2019, 50(17): 4003–4007.
[25] Zhu H, Liu T, Li P, et al. Re-evaluation of preparation processes of Shuanghuanglian series [J]. Chinese Traditional Patent Medicine, 2017, 39(05): 1087–1090.
[26] Liu T, Feng J, Li P, et al. Comparison of four processes for Yuanhu Zhitong series [J]. Chinese Traditional Patent Medicine, 2017, 39(4): 851–854.
[27] Wang K, Gao L, Qin X, et al. Research progress on color difference and safety of TCM injections [J]. Chinese Traditional and Herbal Drugs, 2019, 50(9): 2219–2223.
[28] Wu Y, Jin S. Progress on pharmacology, pharmacokinetics and analytical methods of polysorbate 80 [J]. Chinese Pharmaceutical Affairs, 2008, 22(8): 717–720.
[29] Ye L, Xiong Z, Sun E, et al. Key technologies for dosage form design of TCM liquid preparations: solubility and solubilization of components [J]. China Journal of Chinese Materia Medica, 2022, 47(12): 3166–3174.
[30] Wu Y, Lü S, Li Y, et al. Separation and characterization of nano-phase in Baihu Decoction [J]. Chinese Archives of Traditional Chinese Medicine, 2021, 39(12): 121–124.
[31] Wu C, Zhang Y, Yin B, et al. Clinical study on new indication of Jingqianping Granules for menopausal syndrome [J]. Chinese Traditional Patent Medicine, 2009, 31(11): Suppl. 7–Suppl. 8.
[32] Liu Y, Sun M, Zhao Y, et al. Application status and considerations of network pharmacology in TCM drug repositioning [J]. Chinese Journal of Evidence-Based Medicine, 2017, 17(11): 1344–1349.
[33] Zhang W, Wu H, Yu X, et al. Network pharmacology-based precise clinical positioning and active component study of Gualou Xiebai Banxia Decoction [J]. Complex Systems and Complexity Science, 2018, 15(1): 2–10.
[34] Liang X J, Li H Y, Li S. A novel network pharmacology approach to analyse traditional herbal formulae: The LiuWei-Di-Huang Pill as a case study [J]. Molecular BioSystems, 2014, 10(5): 1014–1022.
[35] Jia X, Yang B, Feng L, et al. Frontiers in TCM pharmaceutics: technical basis and key scientific issues of component formulation [J]. Acta Pharmaceutica Sinica, 2018, 53(12): Insert 1–Insert 2.
[36] Ke Z, Hou X, Qiu H, et al. Development ideas for modern TCM preparations based on component-structure theory [J]. Journal of Chinese Medicinal Materials, 2017, 40(11): 2736–2739.
[37] Li M, Sun E, Xu F, et al. Changes in flavonoid components of Epimedium before and after processing based on UPLC-Q/TOF-MS [J]. Chinese Traditional and Herbal Drugs, 2020, 51(11): 2900–2907.
[38] An Y, Jia X, Yuan H, et al. Research ideas on antiviral material basis of Banlangen [J]. Chinese Traditional and Herbal Drugs, 2008, 39(4): 616–619.
[39] Jia X, Liu G, Chen Y, et al. Material basis of Prunella genus for prevention/treatment of lung cancer based on component-structure theory [J]. Journal of Chinese Medicinal Materials, 2010, 33(07): 1105–1109.
[40] Liu D, Feng L, Song J, et al. Research ideas and strategies for component holistic biopharmaceutics classification system [J]. Chinese Traditional and Herbal Drugs, 2017, 48(23): 4831–4835.
[41] Chen J, Gu J, Wang C, et al. Component-structure TCM and network pharmacology: systematic holistic regulation of pathological mechanism networks [J]. China Journal of Chinese Materia Medica, 2015, 40(4): 758–764.
[42] Wang L, Zhou G B, Liu P, et al. Dissection of mechanisms of Chinese medicinal formula Realgar-Indigo naturalis as an effective treatment for promyelocytic leukemia [J]. PNAS, 2008, 105(12): 4826–4831.
[43] Zhang Q Y, Mao J H, Liu P, et al. A systems biology understanding of the synergistic effects of arsenic sulfide and Imatinib in BCR/ABL-associated leukemia [J]. PNAS, 2009, 106(9): 3378–3383.
[44] Zhang X, Zhang Z, Lin X, et al. Key technical issues in development of classical famous formula preparations [J]. Chinese Traditional and Herbal Drugs, 2021, 52(21): 6724–6731.
[45] Sun X, Yang B, Li Y. Progress in quality evaluation of multi-origin TCM [J]. Chinese Traditional and Herbal Drugs, 2024, 55(12): 4214–4224.
[46] Lou F, Ling Y, Tang Y, et al. Separation, purification and structural identification of ginkgolides [J]. Chinese Journal of Natural Medicines, 2004, 2(1): 11–15.
[47] Yu D, Liu D, Zhang Z, et al. Design techniques for TCM component dosage forms based on biopharmaceutic properties [J]. China Journal of Chinese Materia Medica, 2012, 37(19): 2993–2996.
[48] Hou X, Wang G, Qiu H, et al. Innovative component-structure TCM formulation technology for high bioavailability [J]. Chinese Traditional and Herbal Drugs, 2017, 48(16): 3280–3287.
[49] Liu D, Yu D, Sun E, et al. Construction of TCM components and component biopharmaceutics classification system [J]. China Journal of Chinese Materia Medica, 2012, 37(19): 2997–3000.
[50] Song H T, Zhang Q, Wang H J, et al. Preparation of Shuxiong sustained-release capsules by multiparticulate time-controlled explosion technology [J]. Pharmazie, 2007, 62(5): 372–377.
[51] Tang X, Tian X L, Ci L. Preparation and evaluation of pH-dependent gradient-release pellets for TCM [J]. Drug Development and Industrial Pharmacy, 2004, 30(10): 1079–1087.
[52] Wei Y, Zhang N, Lin X, et al. In vitro release characteristics and rat pharmacokinetics of a multi-unit release system for Dachuanxiong Formula [J]. Acta Pharmaceutica Sinica, 2011, 46(9): 1150–1155.
[53] Feng L, Zhang M, Gu J, et al. Multidimensional dynamic quality control of Danshen preparations based on component-structure theory [J]. China Journal of Chinese Materia Medica, 2013, 38(21): 3622–3626.