Traditional Chinese Medicine (TCM) has a long history in our country, guided by the theoretical principles of TCM, demonstrating unique advantages and specific therapeutic effects in disease prevention, treatment, and health recovery, which has garnered widespread attention.[1] The efficacy of a drug primarily depends on its inherent properties; however, under certain conditions, the dosage form can also play a crucial role in the drug’s effectiveness, particularly in terms of drug release and absorption. The same drug can exhibit significant differences in stability, onset time, duration, site of action, intensity of effect, and side effects due to variations in dosage forms, excipients, preparation methods, and operational techniques.[2].
The dosage form of TCM is the final application form of the herbal preparation, tailored according to the patient’s condition, the nature of the herbs, and the route of administration, to achieve optimal therapeutic effects in clinical practice. The development of TCM dosage forms has a long history, gradually forming various forms such as decoctions, tinctures, teas, powders, pastes, pills, and granules. With advancements in modern technology, optimized extraction processes, and reforms in pharmaceutical methods, new dosage forms such as suppositories, syrups, ointments, oral liquids, and granules have emerged.[3] This article primarily compares the widely used traditional dosage forms of decoctions, extracts, and the rapidly developing granules, summarizing the advantages and disadvantages of these three forms, and discussing their applications and future development prospects.
1 Introduction to Decoctions, Extracts, and Granules
1.1 Decoctions
Traditional Chinese Medicine decoctions, known as汤液 (tāng yè), originated during the Yin and Shang dynasties. As the oldest and most widely used dosage form in TCM, it has a history of several thousand years. Decoctions are liquid preparations made by boiling or soaking the corresponding herbal pieces in water, then straining the liquid to obtain the medicinal extract[4]. The interaction among the herbs achieves the purpose of treating and preventing diseases. Decoctions are characterized by flexible formulation, the ability to adjust dosages according to symptoms, rapid onset of action, and ease of absorption[5]. Thus, the ancient saying goes: “Decoctions are for cleansing, used to treat major illnesses.” Decoctions remain the most commonly used dosage form in modern TCM clinical practice, accounting for about 50% of all TCM prescriptions. However, the need for freshly prepared decoctions, difficulties in preservation, lengthy preparation times, and inconvenience in transportation have limited their clinical application and development.
1.2 Extracts
Extracts are preparations made by using suitable solvents to extract the active components from herbal materials or by boiling them in water, followed by solid-liquid separation, concentration, and drying[7]. Extracts can be classified into dry extracts and concentrated extracts, with dry extracts containing about 5% moisture, while concentrated extracts generally contain 15% to 20% moisture. Due to their lower solvent content, they can be stored for longer periods. Unless otherwise specified, each gram of extract is equivalent to 2 to 5 g of raw herbs, overcoming the drawbacks of large volume and inconvenience associated with decoctions, making it easier for patients to take. This dosage form can be taken directly or formulated, suitable for both internal and external use, with various methods of administration. Its effects vary with different diseases; for instance, single extracts increase the effective components per unit volume, reduce the amount of herbs needed, and enhance efficacy, while compound extracts broaden the treatment scope and facilitate consumption, storage, and transport.
1.3 Granules
TCM granules, also known as single herb concentrated granules, ready-to-use granules, or concentrated granules of herbal pieces, are improved from traditional decoctions. They combine modern pharmaceutical technology to extract, separate, concentrate, dry, granulate, and package single herb raw materials[8]. Granules overcome the cumbersome and time-consuming preparation of traditional decoctions, as well as issues with preservation and transport. They feature precise dosing, safety, hygiene, convenience for carrying, ease of storage, and instant preparation, making them more suitable for today’s fast-paced lifestyle. With further research into the production management standards, quality standards, and therapeutic effects of TCM granules, their advantages compared to traditional decoctions are becoming increasingly evident, leading to wider acceptance among patients and more extensive clinical applications[10].
2 Characteristics of Decoctions, Extracts, and Granules
2.1 Decoctions
TCM decoctions are characterized by rapid action, flexible formulation, and relatively low cost. The simultaneous boiling of herbal pieces leads to a series of physical and chemical changes, enhancing efficacy, reducing toxicity, and moderating the properties of the herbs, reflecting the compatibility of the drugs[11]. However, the complexity and time-consuming nature of preparation, the need for fresh use, and difficulties in preservation and transport, along with quality issues of raw materials and herbal pieces, have limited the application of decoctions.
2.2 Extracts
Extracts are an improvement over decoctions, accepted by patients due to their smaller dosage and convenience. However, extracts still face issues such as varying concentrations depending on the manufacturer, inability to adjust dosages according to symptoms, and challenges in establishing quality standards. Additionally, the commonly used water extraction and alcohol precipitation methods can lead to the loss of effective components due to sedimentation or adsorption during refinement[13]. Due to their hygroscopic nature, they may soften and clump together, generally serving as intermediate products for granules.
2.3 Granules
Compared to traditional decoctions, TCM granules do not require boiling and can be taken with hot water, are small in size, and convenient for carrying and storage. They have a clear shelf life and are easier to control in terms of quality[14]. However, traditional decoctions involve a process of simultaneous boiling, while granules are merely a simple mixture of single herb components, and the two are not equivalent[15]. The boiling process of TCM can lead to a series of complex physical and chemical reactions among the components, which can reduce toxicity for some herbs with toxic components. In contrast, mixing single extracts may increase the risk of toxicity[17]. Currently, clinical research on granules lacks multi-center, double-blind, randomized, controlled methods and results, making it difficult to provide convincing data, and the equivalence of decoctions and granules still requires further validation[10].
Table 1 summarizes the main advantages and disadvantages of traditional decoctions, extracts, and granules.
3 Comparative Analysis of Decoctions, Extracts, and Granules
3.1 Price Factors
Traditional decoctions use herbal pieces, which are processed and prepared according to TCM theory and can be used directly in clinical practice[18]. Due to the relatively simple processing steps, the price of herbal pieces is lower, making them more suitable for the general public, and with a history of thousands of years, decoctions continue to be widely used.
TCM granules are produced using extraction methods, selecting suitable solvents and methods to extract soluble effective components from herbal pieces, which are then concentrated and dried to form granules[19]. Due to the relatively complex and cumbersome pharmaceutical process, their price is higher, approximately 1.5 to 2 times that of traditional herbal pieces. For example, the price of TCM granules for the commonly used formula Si Jun Zi Tang is 1.85 times that of the herbal pieces for the same amount of herbs[21]. Wang Bin[22] conducted a study on 600 prescriptions from the Zunyi Hospital of TCM in Guizhou Province from 2015 to 2016, finding that the average price of prescriptions using TCM granules was 160.51 yuan, while the average price for herbal piece prescriptions was 80.15 yuan, indicating that the price of granules was significantly higher than that of herbal pieces. Liu Huihui[23] analyzed the prices of TCM in a tertiary hospital in Guangdong in October 2010 and found that among 407 types of herbs, 383 types of granules were priced higher than the pieces, accounting for 94.10%, with 20 types having prices more than 5 times higher, including Liu Ji Nu (7.27 times) and Qing Tian Kui (7 times). Due to price factors, the promotion of TCM granules has also faced certain limitations.
3.2 Storage Conditions
TCM decoctions generally need to be prepared fresh for immediate use, are prone to mold, and cannot be stored for long periods. Additionally, the herbal pieces used in decoction preparation can undergo physical and chemical changes during storage due to external factors such as temperature, humidity, sunlight, and pests, leading to various forms of deterioration such as moisture, adhesion, oil rancidity, discoloration, mold, and insect damage[24].
Extracts, due to their low or negligible solvent content, have relatively stable effective components and can be stored longer than decoctions. However, extracts are highly hygroscopic, especially dry extracts, and thus need to be stored in opaque containers to prevent moisture absorption[25], or coated with thin film to significantly reduce their hygroscopicity and improve stability[13]. TCM granules, through high-speed centrifugation, ultrafiltration, concentration, and spray-drying techniques, reduce moisture content[26], shrinking their volume to 1/10 of the original herbal pieces, thus extending their shelf life. Moreover, the packaging of TCM granules is typically vacuum-sealed with aluminum foil, providing moisture-proof, light-proof, mold-proof, and insect-proof characteristics, allowing for long-term storage and easier transport.[27].
Herbs with high volatile oil content, such as Jing Jie and Bo He, have shorter shelf lives, and their effective components gradually decrease during storage. Therefore, herbal pieces are usually required to be purchased in small quantities multiple times. Due to the special nature of herbal pieces, storage rooms typically require regular ventilation, maintaining a room temperature of 15 to 20 °C and a relative humidity of 45% to 75%, avoiding direct sunlight, and regularly checking the ventilation, temperature, humidity, moisture-proof, pest-proof, and rodent-proof conditions and facilities[28]. Zhuang Junrong et al.[29] found that in 2013, the total return rate of herbal pieces at the Shuguang Hospital affiliated with Shanghai University of TCM was about 1%, with a loss rate of 0.03%; while TCM granules, due to their aluminum foil packaging, have a long shelf life, virtually eliminating issues of insect damage and mold, with a total return rate of less than 0.01% and a loss rate of 0.
3.3 Convenience
Traditional decoctions allow for flexible adjustments based on symptoms, providing significant individualized advantages. However, they require fresh preparation, have lengthy cooking times, are cumbersome to prepare, and are prone to spoilage, making them inconvenient for both carrying and consumption. Additionally, traditional decoctions may suffer from inaccuracies in formulation, leading to significant human error and uneven dosages[11].
Extracts ensure the effective components of decoctions while overcoming the drawbacks of large volumes and cumbersome preparation. Through methods such as water extraction and alcohol precipitation, they can reduce the amount of medication needed and lower hygroscopicity.
TCM granules are made by extracting, concentrating, drying, and granulating herbal pieces, thus overcoming the cumbersome preparation of decoctions. They can be taken directly with hot water without boiling, are small in size, occupy less space, and are convenient for carrying, consumption, and storage[30]. For example, at the Shuguang Hospital, the area occupied by herbal pieces is 150 m2, while granules only occupy 20 m2, indicating that granules save pharmacy space, reduce labor, and facilitate patient use in various situations[29]. Granules are vacuum-sealed, providing good sealing properties, avoiding spoilage, rancidity, and insect damage associated with improper storage of herbal pieces, making them easier to store, with more accurate formulations, and avoiding dosage errors caused by weighing and handling herbal pieces[31]. However, since the common specification is 10 g per package, this restricts adjustments based on symptoms, leading to inaccuracies in dosage for special populations such as infants, the elderly, and pregnant women when using standard packaging[32].
3.4 Chemical Composition
Extracts are generally intermediate products for preparing granules, and analyzing the chemical composition of extracts can reflect the corresponding components of granules. Therefore, extracts are often used in experiments as substitutes for granules[33]. Liang Hui et al.[34] studied the differences in chemical composition among Yin Chen Hao Decoction, combined decoction granules, and separate decoction granules, finding that the similarity among the three exceeded 0.9, with combined decoction granules showing higher similarity than separate decoction granules, indicating that both can be used clinically, and the clinical effects of combined decoction granules may align more closely with traditional decoctions. Huang Zhaoyi et al.[35] compared the dissolution rates of berberine hydrochloride in traditional decoctions and TCM granules of Jiao Tai Wan, finding that the relative dissolution rate of berberine hydrochloride in granules was higher than that in traditional decoctions, possibly due to the smaller interactions during the formulation of TCM granules compared to the combined decoction process, avoiding neutralization reactions between berberine hydrochloride and cinnamic acid during boiling, resulting in less loss of effective components. Yang Yuqin et al.[36] measured the total alkaloid content in Si Ni Decoction, compound granules, and granules, finding significant differences among the three, with total alkaloid content in traditional decoctions and compound granules being comparable, both lower than that in granules, possibly due to interactions among the herbs during the boiling process of traditional decoctions. Granules only extract single herbs, preventing interactions among different herbs during extraction, which may lead to differences in efficacy compared to traditional decoctions.
3.5 Efficacy
Traditional TCM decoctions are prepared by boiling all the herbs together, during which various components can adsorb, enhance solubility, and promote precipitation, affecting dissolution rates and potentially leading to chemical reactions that generate new substances. Whether granules can produce the same efficacy as decoctions requires further research[37].
3.5.1 Clinical Efficacy Li Zhi et al.[38] compared the antipyretic effects of a ready-to-use granule for cold and fever with those of decoctions, randomly dividing 64 patients with cold and fever into granule and decoction groups. The results showed no statistically significant differences in fever duration and antipyretic time between the two groups, indicating equivalent antipyretic efficacy. Zhou Aijun et al.[39] compared the clinical efficacy of Da Qing Long Decoction granules and traditional decoctions in treating influenza, observing 120 patients, randomly divided into two groups: 64 in the granule group and 56 in the decoction group. Analysis showed that the antipyretic effects of the Da Qing Long Decoction granule group were slightly better than those of the decoction group, but not statistically significant; the overall efficacy of the granule group in treating influenza was slightly lower than that of the decoction group, but still without statistical differences. Dong Xiao et al.[40] compared the clinical efficacy of He Jie Fang decoction and granules in treating chronic hepatitis B, observing significant improvements in symptoms and signs in both groups after treatment, with no statistically significant differences in overall efficacy and effective rates. This indicates that the clinical efficacy of granules and traditional decoctions is not significantly different.
3.5.2 Pharmacological Studies Wang Guangming et al.[41] used a model of diabetic mice with spleen deficiency to compare the pharmacological effects of Shen Ling Bai Zhu San granules and decoctions on small intestine propulsion. The results indicated that both granules and decoctions significantly inhibited small intestine propulsion in diabetic mice with spleen deficiency, with the granule group showing superior efficacy compared to the decoction group, comparable to the positive drug atropine. Yang Dianxing et al.[42] studied the cough-suppressing and antipyretic effects of Re Ke Qing granules and extracts in mice, finding that the overall efficacy of Re Ke Qing granules was generally comparable to that of the same dose of traditional extracts, with better antipyretic effects than extracts, but lower cough-suppressing effects than the same dose of extracts, possibly due to the complex physical and chemical reactions among the herbs during the boiling process of extracts. Zhou Hongzu et al.[43] compared the inhibitory effects of Zuo Jin Fang granules and traditional decoctions on human gastric cancer cells SGC-7901, finding that both granules and decoctions could inhibit the activity of SGC-7901 cells, with granules showing more significant effects than traditional decoctions.
3.6 Clinical Sales Situation
Li Hongwei et al.[44] analyzed the sales of TCM herbal pieces and granules at Tianjin Public Security Hospital in 2010, comparing usage across departments, sales quantities of commonly used herbs, medication frequency, and limited daily costs. The results indicated that sales of herbal pieces outperformed those of granules, with different departments showing varying preferences for the two dosage forms, while the clinical demand for commonly used herbs was roughly equivalent for both forms. The frequency of use for herbal pieces was higher than that for granules, but the limited daily costs showed the opposite trend, indicating that both dosage forms have a certain status in clinical applications due to their respective characteristics. Zhang Liuyan et al.[45] conducted a statistical analysis of the sales of TCM herbal pieces and granules at their hospital from 2014 to 2015, surveying 200 patients regarding their acceptance of TCM granules. The results showed that the sales volume of TCM granules was 8.53 times that of herbal pieces, with sales revenue being 10.96 times higher, and the average prescription price exceeding that of herbal pieces by 25.53%. Patients over 60 years old showed significantly lower acceptance of TCM granules compared to those under 60, with statistically significant differences.
4 Conclusion
Extracts and granules are improvements over traditional decoctions, overcoming the drawbacks of the need for boiling and difficulties in preservation. Extracts generally serve as intermediate products for granules and are often used in experiments. TCM granules, due to not undergoing simultaneous boiling, have certain differences in efficacy compared to traditional decoctions, but in most cases, their clinical efficacy is comparable to that of traditional decoctions. Additionally, granules occupy less space, are easy to store and carry, saving storage space and labor, which may be one direction for reducing the price of granules.
However, issues such as high prices, limited specifications, and the need for further research on whether granules can replace decoctions have also restricted their development and application. With advancements in technology and deeper research, TCM granules are expected to have a promising application future. In the future, long-term systematic studies on the pharmacology and efficacy of granules should be conducted, unified scientific quality standards established, and modern technological means and labor-saving approaches employed to reduce the price of granules, overcoming their shortcomings and promoting better development and social acceptance of TCM granules.
References (omitted)
Source: Yin Jia, Pan Ye, Cai Xuemeng, Gao Shan, Yu Chunquan. Comparison of Traditional Chinese Medicine Decoctions, Extracts, and Granules [J]. Chinese Herbal Medicine, 2017, 48(18):3871-3875.
