Exploration on medication patterns of “External Treatment” in the ancient Chinese medical book Liu Juanzi Guiyi Fang

Qiang Lin, Jun-Lin Mo, Ji-Wei Qiu, Jue-Ying Chen, Yong-Xiang Xie*

REVIEW

Exploration on medication patterns of “External Treatment” in the ancient Chinese medical book

Qiang Lin1, Jun-Lin Mo2, Ji-Wei Qiu2, Jue-Ying Chen2, Yong-Xiang Xie1*

1The First Affiliated Hospital of Guangxi University of Chinese Medicine, Guangxi Nanning, China; 2Guangxi University of Chinese Medicine, Nanning, China.

To obtain the medication patterns of “External Treatment” by analyzing the prescriptions for the “External Treatment” in a Chinese ancient book called(, written by Liu Juanzi in 499 C.E.).The prescriptions for “External Treatment” and primary traditional Chinese medicines inwere analyzed using data mining methods, such as frequency analysis and cluster analysis, after screening for prescriptions related to “External Treatment” in. The Database of Prescriptions for External Treatment in Liu Juanzi Guiyi Fang was then established.The earliest Chinese characters for “Yin” and “Yang” were found on “oracle bones”. These bones were the skeletal remains of different animals, and were used in ancient Chinese divination practices going all the way back to the 14th century B.C. Simply put, “Yin” is the cold and “Yang” is the warm. In traditional Chinese medicine, this concept of dualism and its fundamental principle underlie physiology, pathology, and the treatment of illnesses. The “External Treatment” discussed inprimarily adopts the methods of “Warming Yang”, “Cooling Heat (Yang)”, and “Qu Xie (dispelling pathogenic factors of epidemic diseases)”, as well as “Huo Xue (promoting blood circulation) and promoting tissue regeneration. In Chinese medicine, “Si Qi (cold as winter, cool as autumn, warm as spring, hot as summer)”, “Wu Wei (five flavors: sweet, pungent, salty, sour, and bitter)” used to describe the properties of herbs. Inmost of the medicines used were more “Sweet”, “Pungent”, “Warm”, and the “Channel Tropism” were primarily distribute to the “Liver”, “Heart”, “Stomach”, and “Large intestine meridian”.The data mining method systematically summarized the medication characteristics of the prescriptions for “External Treatment” in. The characteristics of the “External Treatment” in this book include “supporting healthy Qi” and “promoting Qi and Blood circulation” which as the top priority, applying both “Attacking and Supplementing methods” as the focus, and combining “Supplementing methods” with “Elimination methods”. It has provided theoretical guidance in “External Treatment” for surgery of traditional Chinese medicine.

Cluster analysis, External Treatment, Frequency analysis, Liu Juanzi Guiyi Fang, Medication patterns

Based on the theories of traditional Chinese medicine, the ancient books of traditional Chinese medicine highlight “Dialectical Treatment with Unique Changes in Additions and Subtractions”. Through analysis of, we have gained a new understanding of the “External Treatment Surgery” in traditional Chinese medicine.

Background

((LJGBP), written by Liu Juanzi in 499 C.E.) is said to have been compiled by Gong Qingxuan of the Southern Qi Dynasty (479 C.E.?502 C.E.). It is a monograph on surgery in traditional Chinese medicine (TCM), which has a long history in China. The book discusses the etiology, pathogenesis, diagnosis, and treatment of surgical conditions, such as incised wounds, carbuncles, and gangrene, in detail. The clinical experience and prescriptions for both internal and “External Treatment” (ET) from doctors of that and previous generations are included, with details on various usage and dosage forms. This book has had a significant influence on the development of surgery within TCM in more recent generations, but a systematic and comprehensive study has rarely been conducted on it. Therefore, in this study, we used data analysis method to conduct statistical analysis on the prescriptions and usage in LJGBP, and attempted to explore its medication characteristics to provide a reference for clinical medication in surgery of TCM.

Methods and materials

Data sources and research contents

was used to collect information regarding the medicines and therapeutic usages included in LJGBP[1]. The medicines were then studied and analyzed to further evaluate the characteristics of their use for ET.

Medicine selection criteria

Inclusion criteria. The following were included in this study: 1) medicines with accurate names or aliases, and 2) medicines with marked processing methods were included.

Exclusion criteria. All prescriptions that met 1 or more of the following criteria were excluded from this study: 1) medicines not included in the 2015 edition of[2] and the[3] in the Twelfth 5-Year Plan for higher education in the Chinese pharmaceutical industry, 2) medicines with names that cannot be confirmed or known at present, and 3) medicines that were indicated for oral administration in the prescriptions.

Methods

Standardization of medicine names. The medicine names in LJGBP were standardized according to the 2015 edition of theand thein the Twelfth 5-Year Plan for higher education in the Chinese pharmaceutical industry for correcting names. Aliases appearing in the prescriptions were standardized with common names. Crude products of medicines were uniformly used if there were little difference before and after the decoction pieces were processed. If there were great differences, the crude and processed products of medicines were separated.

Treatment of “Medicine Property”, “Taste” and “Meridian Tropism”. “Medicine Properties, Taste, and Meridian Tropism” were analyzed according to the 2015 edition of theand thein the Twelfth 5-Year Plan for higher education in the Chinese pharmaceutical industry. Eight categories of “Medicine Properties” were determined: “Cold, Hot, Warm, Cool, Balanced, Slightly Warm, Slightly Cold, and Super-Hot.” Nine types of “Medicine Taste” were determined: “Sour, Bitter, Sweet, Pungent, Salty, Astringent, Light, Slightly Bitter, and Slightly Sweet”. The 12 “Meridians” of TCM were included: “Heart, Lung, Spleen, Stomach, Liver, Gallbladder, Kidney, Bladder, Large Intestine, Small Intestine, Triple Warmer, and Pericardium.”

Qualitative processing of the “Properties”, “Taste”, and “Meridian Tropism” of TCM was conducted according to a method previously described in the literature [4?5]. The “property” of “Cold, Hot, Warm, Cool, and Balanced” were valued at 1, with the remaining properties valued at 0. The following “Tastes” were given a value of 1: “Sour, Bitter, Sweet, Pungent, and Salty”. The remaining “Tastes” were valued at 0. “Light” was attached to “Sweet”, with a value of 0.5. “Astringent” was attached to “Sour” and given a value of 0.5. Regarding the “Meridian Tropism”, the medicines are marked with a “1” under the corresponding “Meridian”, with the rest being valued at 0. “Slightly Warm”, “Slightly Cold”, and “Super-Hot” were classified as “Warm”, “Cold”, and “Hot”, respectively. In terms of “Taste”, “Slightly Bitter” and “Slightly Sweet” were classified as “Bitter” and “Sweet” (Table 1). This quantitative processing was conducted to prepare the data for later clustering analysis.

Database establishment

Using Microsoft Excel 2010 (Redmond, WA), 2 machines were used by 2 people to input the medicines used in the prescriptions recorded in LJGBPto establish a database, the. The TCM database includes the name, “Property”, “Taste”, and “Meridian Tropism” of each TCM. Then, according to the description of medication methods in various articles within LJGBP, the ET prescriptions were selected and marked beside the corresponding medicines when data were input. Finally, the accuracy of the data was checked and edited. If there were any disputes, they were judged by a third person.

Data analysis

Table 1 Example of a digital list of frequently used medicines in Liu Juanzi’ Ghost-Bequeathed Prescriptions

SPSS 20.0 and Microsoft Excel 2010 were used to analyze the distribution, frequency, and clustering of medications in the database. The specific method of medicine distribution and frequency analysis was to conduct distribution analysis on all medicine in the database, including “Medicine Properties”, “Medicine Taste”, “Meridian Tropism”, and usage, to obtain the frequency of medicine use, as well as relevant data on “Medicine Properties”, “Medicine Taste”, “Meridian Tropism”, and usage. On this basis, all medicine related to external prescriptions in LJGBP were studied and analyzed. The specific method for clustering analysis of high-frequency medicine was to systematically cluster medicine frequently used with a frequency over 10, and select Q-type clustering, taking the Euclidean distance square as the measurement method, Ward’s method as the clustering method, and using a dendrogram to display data results and all clusters. Using cluster analysis, we can classify similar data into one category and estranged data into different categories to determine the clinical medication patterns in LJGBP.

Results

Inclusion results

After screening, 54 prescriptions were selected and 74 medicines were included. The total frequency of using the medicines was 409 times.

Statistical results of ET

Analysis of medicine types. A total of 74 medicines were used in the prescriptions for ET, with a frequency of 409 uses, 90 of which were used as tonic medicines (Figure 1).The utilization rate of “Tonic Medicines” are the highest. Other medicines with high utilization rate are “Exterior-Related Medicines, Heat-Clearing Medicines Interior-Warming Medicines, Purgative Medicines, Blood-Activating and Stasis-Removing Medicines, and Insecticidal and Antipruritic Medicines” (Figure 1).

Medicine “Taste” analysis. “Taste” analysis of medicines was also conducted (Figure 2 and Figure 3).The frequency of use for “Warm and Hot Medicines” was the highest, accounting for 54.5% of the total medicine use. The use of “Cold Medicines” ranked second, accounting for 38.9% of the total medicine use. The remaining medicines were “Balanced and Cool Medicines” (Figure 2). “Pungent”, “Bitter”, and “Sweet” medicines were used most frequently, with “Pungent Taste” accounting for 39.9%, “Bitter Taste” for 29.5%, and “Sweet Taste” for 23.5% of the total (Figure 3).

Medicine meridian tropism analysis. The analysis of meridian tropism was shown in Figure 4.The medicines were mostly distribute to the “Spleen Meridian” (approximately 16.8%), followed by “Liver Meridian” (approximately 14.9%), “Heart Meridian” (approximately 13.6%), “Stomach Meridian” (approximately 13.2%), “Large Intestine” (approximately 11.3%), “Lung Meridian” (approximately 11.2%), and “Kidney Meridian” (approximately 9.1%).

Analysis of commomly used medicines. Of the medicines, those that were used more than 10 times were identified as commomly used medicines. The use frequency was shown in Table 2 and Figure 5.

The most frequently used medicines in the book are Baizhi (), with a frequency of 28, accounting for 6.8% of the total number of frequently, followed by Danggui (), Dahuang (), Chuanxiong (), Huanglian (), Fuzi (), Baisha (), Xionghuang (), and Xixin ().

Cluster analysis of frequently used medicines in the ETs. Cluster analysis was conducted on medicines used more than 10 times for ET in LJGBP. The results are shown in Figure 6 and can be divided into 4 categories. The first category is composed of “Yang-Warming” and “Blood-Activating” medicines, which are, Huajiao (),, and. The second type is medicines that “Dispel Pathogenic Factors with Pungent Divergence”, including,, and. The third category includes “Teat-Clearing” and “Tissue Regeneration” medicines, such as Shengdihuang () and Bailian (). The fourth category includes “Heat-Clearing” and “Blood-Nourishing” medicines, including,,, and Huangqin ().

Figure 1 Medicines with different efficacies used in the “External Treatment”of

Figure 2 “Taste” analysis of medicines used in “External Treatment”

Figure 3 Frequencies of different medicines used in “External Treatment”

Figure 4 “Meridian Tropism”frequencies of medicines used in “External Treatment”

Table 2 Frequencies of medicines used in “External Treatment” in Liu Juanzi’ Ghost-Bequeathed Prescriptions (n > 10)

Discussion

LJGBP was written by Liu Juanzi in 499 C.E. and was compiled by Gong Qingxuan in the Southern Qi Dynasty (479 C.E.?502 C.E.). It is a work with a history of more than 1,500 years and is of milestone significance in the field of traditional surgical treatment in China. The book puts forward 3 major therapeutic principles of surgery in TCM: “Elimination”, “Supporting” and “Supplementing”, and also paying attention to the regulation of “Qi” and “Blood”. This work provided significant contributions to the treatment guidance for sores, ulcers, carbuncles, traumas, and other surgical diseases.

This study analyzed the frequency of medicines used for ET in the book in terms of “Property”, “Taste”, and “Meridian Tropism”. For example, “Tonic Medicines” were the most frequently used type, followed by “Exterior-Related Medicines”, “Heat-Clearing Medicines”, “Interior-Warming Medicines”, “Purgative Medicines”, “Blood-Activating”, and “Stasis-Removing Medicines”, “Insecticidal and Antipruritic Medicines”. “ETMedicines”werecharacterizedbyboth “Attacking and Tonifying Features”, with “Tonifying Deficiencies” as the primary therapy method and “Attacking Pathogenic Factors” as the supplementary therapy method, as shown in Figure 1. It is clear from the analysis of “Medicine Taste” shown in Figure 2 and Figure 3 that “Warm Medicines and Pungent, Bitter, and Sweet Medicines” accounted for the majority, because “Pungent Medicines can Unblock Qi and Blood when used in External Treatment” and can, at the same time, “Disperse Heat Toxicity” from the body surface and eliminate pathogenic factors. “Bitter Medicines” can “Clear Heat, Purge Heat, and Detoxify, Treat Carbuncles, Gangrene”, and stimulating factors caused by “Heat Toxin”, and “Bitter Medicines” can “Eliminate Dampness”, which can be used to treat surgical diseases such as eczema. “Sweet Taste” mostly appeared together with “Pungent Taste”. Most of the medicines in this category were “Warm and Sweet”; “Warm Medicines” can “Supplement Deficiencies” and resist pathogenic factors. The frequency of medicine “Meridian Tropism” in Figure 4 shows that “Meridians Tropism” was mostly seen in the “Spleen, Liver, Heart, Stomach, Large Intestine, Lung, and Kidney”. “Spleen and Stomach are the Sources of the Constitution, as well as for Generating Qi and Blood”. “The Liver is a Sea of Blood and Stores Blood”. “The Heart, as the Body’s Monarch, Controls the Blood, Promotes Qi, and Enables the Blood to Move to the 5 Internal Organs while Nourishing the Entire Body”. “Spleen and Stomach, Liver, and Heart, are all related to Qi and Blood”. It is clear that ET focused on “Regulating Qi and Blood”. From the analysis of frequently used medicines (Table 1), the high frequency medicines are,,, andy. Modern pharmacological research indicates that the active ingredients of[6],[7],[8],[9],,[10] and[11] have both antibacterial and anti-inflammatory effects.

Figure 5 Label cloud map of traditional Chinese medicines with a frequency of > 10 for “External Treatment” in

Figure 6 Cluster analysis of high-frequency medicines (n > 10) for “External Treatment” in

Cluster analysis results demonstrated that the first category was mainly “Yang-Warming” and “Blood-Activating” medicines, including,,, and.can nourish the “Blood” and promote “Blood” circulation in the early stage of surgical diseases such as sores and ulcers. While the remaining 3 medicines can warm the blood vessels in the late stage. If “Qi” and “Blood” are warmed, dead muscles will disappear, and new flesh will emerge. The second category was medicines that dispell pathogenic factors with pungent divergence, including,, and. These 3 medicines are all anti-pathogenic and can be used mainly in the early stage of surgical diseases such as sores, ulcers, and carbuncles. They are primarily used for treating surgical diseases caused by external pathogens invading the body. The third category includes “Heat-Clearing” and tissue regeneration medicines, such asand. In the book,was mostly used for the treatment of late stage of ulcers or flesh decay, whereaswas mostly used for the treatment of early-stage incised wounds or superficial skin injury. Therefore, this type of medicines can be used not only in the early stages for sores and carbuncles caused by heat toxins, but also in the late stages of blood and flesh decay. The fourth category was “Heat-Clearing” and “Blood-Nourishing” medicines, including,,, and. The first 3 medicines are “Bitter and Cold” medicinal products. ET using these can “Clear and Purge the Local Fire Toxin” from sores and ulcers. Toxic materials produced by “Fire-Evil” can damage “Yin and Blood”, and “Bitter Cold can Strengthen Yin”.with the “Property of Acid” and belonging to “Liver Meridian” can “Nourish the Blood”, which can solve the primary pathogenesis of toxic materials produced by “Fire-Evil” resulting in damage of “Yin and Blood” in surgical diseases such as sores, ulcers, and carbuncles.

Based on the analysis of the prescriptions and their usage as described in LJGBP, we puts forward the ET principles for carbuncles, sores, and ulcers. The first is to support healthy “Qi” as the top priority, the second is to promote “Qi and Blood” circulation as essential, and the third is applying both “Attacking and Supplementing Methods” as the focus, and combining the “Supplementing Method with An Elimination Method”.

“Supporting Healthy Qi”

In the medication described in LJGBP, “Tonic Medicines” account for a large proportion, with the “Spleen Meridian” being the main “Meridian Tropism”. After investigation, it was determined that the book postulates that “Unhealthy Qi” is the main cause of carbuncles, sores, and ulcers. If exogenous pathogens are present, “Healthy Qi” can drive the pathogens out immediately, not allowing them to remain and block the “Healthy Qi” or cause pus owing to “Heat”. If the pus has already formed, or if the pus has collapsed and the flesh has decayed, the “Healthy Qi” has already been consumed. At this time, attention should be paid to the cultivation and protection of “Healthy Qi”, such as “Invigorating the Spleen Qi and Nourishing the Yin and Blood”, and “Coordinating Qi and Blood into Smooth Movements”, thereby removing decay and promoting new tissue growth, such as empirical formula of Chinese medicineShengrou Dihuang Gao decoction (cream for fresh growing) and empirical formula of Chinese medicine Shengji Huang Gao decoction (cream for muscle growing) for treating carbuncles. If “Healthy Qi” is too weak to support pus for a long time, the pus will not be eliminated and will burst. At this time, it is also necessary to supplement the “Healthy Qi” to allow it to strengthen and expel pathogenic factors, shorten the course of the disease, and prevent syndromes. If the sores and ulcers are caused by “Deficiency”, the “Deficiency of Qi and Blood” will result in the “Stagnation of Blood Stasis”. To solve the fundamental pathogenesis, it is necessary to supplement and normalize “Qi”. If the “Qi” and “Blood” are sufficient, sores and ulcers of the “Yin Syndrome” can be treated naturally. If it is a wound, it can also help the recovery of muscles and bones. Throughout the book, supporting “Qi” is promoted as the primary task in the treatment of surgical diseases in TCM.

Promoting “Qi” and “Blood” circulation as essential

Analysis on the medicines with different “Properties”, “Tastes” and “Meridian Tropism” showed that “Pungent Medicines” are the most commonly used medicines. Medicines for the “Liver Meridian Tropism” are also the most prevalent. “Pungent medicines” can be used to disperse “Qi” and “Blood”, and that the “Liver” governs the circulation of “Qi” and “Blood” to make both “Qi” and “Blood” smooth. At the same time, according to the ranking of frequently used medicines, it was found that the top three medicines were all medicines with the effects of “Promoting Blood Circulation and Qi Circulation”. The occurrence of sores and carbuncles is due to “Qi Stagnation” and “Blood Stasis” caused by internal or external causes, long-term stagnation of “Interior Heat”, and “Excessive Heat” and decay flesh leading to pus. Therefore,, which was frequently used in the book, was identified as a medicine that can nourish the “Blood”, and activate and promote “Blood” circulation.can “Cool Blood, Dispel Blood Stasis, and Promote Blood Circulation”.can “Remove All Qi Stagnation and Blood Stagnation”. In the prescriptions for ET, the use of medicines capable of “Promoting Qi and Blood Circulation” is matched to the pathogenesis of the diseases. The TCMs with the function of “Promoting Qi and Blood Circulation” were frequently used. Modern pharmacological research proves that these medicines demonstrate functions of bacteriostasis, antivirus, inhibition of inflammatory reaction, and regulation of the immune system, and can be used to treat infectious diseases [12]. Therefore, the book considered that “Promoting Blood and Qi Circulation” is an important part of the ET of surgical diseases.

Applying both “Attacking and Supplementing Methods” as the focus, and combining the “Supplementing Method with an Elimination Method”

Through the analysis of medicines used in the book, it has been determined that ET in surgical disease therapy, such as carbuncles, sores, and ulcers, also focuses on both “Attacking and Supplementing”. High-frequency medicines can be obtained through cluster analysis. Attacking the pathogenic factors mainly includes “Clearing Heat” and “Warming Yang”, whereas supplementing the deficiencies includes “Nourishing Blood” and tissue regeneration. Based on the classification of medicines, “Tonic Medicines” are the primary type, with the rest being various kinds of anti-pathogenic medicines. Judged from the “Properties” and “Tastes” of medicines, “Warm and Hot Medicines” were used to “Consolidate the Essence”, whereas “Cold and Cool Medicines” were added to “Attack Evils”. At the same time, “Pungent, Bitter, and Sweet Medicines” were used more frequently. The “Pungent and Bitter Medicines” were mainly anti-pathogenic, whereas the “Sweet Medicines” were mainly “Supplemental”. Therefore, combination of “Attacking and Supplementing Therapy Methods” were also applied of the “ET Methods” described in the book. The book primarily recorded surgical diseases, such as trauma, carbuncles, and scabies. The onset of the diseases was mostly the result of the invasion of external pathogens, which gradually became carbuncles, damaging “Qi” and “Blood”. Therefore, in addition to eliminating pathogens, ET was still needed to “Supplement Deficiencies” and combine “Supplementing” with “Elimination”. The “External Supplementing Method” was used to strengthen the body and repel the pathogens. When the pathogens were repelled to the body surface, the ET for eliminating the pathogens was applied.

Conclusion

Based on the theories of TCM, the ancient books of TCM highlight “Dialectical Treatment with Unique Changes in Additions and Subtractions”. Through analysis of LJGBP, we have gained a new understanding of the “ET Surgery” in TCM. We hope to bring new guidance and thinking to the clinical and ET of TCM through this study. However, we only made simply data mining, and different analysis methods should be used to dig deeper into the data.

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Guangxi Natural Science Fund Project (No.2017GXNSFAA198217). Guangxi Famous Traditional Chinese Medicine Shi Wei Inheritance Studio

LJGBP,; TCM, traditional Chinese medicine; ET, External Treatment.

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The authors declare that they have no conflict of interest.

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Qiang Lin, Jun-Lin Mo, Ji-Wei Qiu, et al. Exploration on medication patterns of “External Treatment” in the ancient Chinese medical book. Drug Combination Therapy 2020, 2 (4): 198–207.

:Xiao-Hong Sheng.

:17 April 2020,

06 May 2020,

:21 October 2020

Yong-Xiang Xie. First Affiliated Hospital of Guangxi University of Chinese Medicine, No. 89-9 Dongge Road, Qingxiu District, Nanning, China. E-mail: 56644367@qq.com.

10.12032/DCT2020B026