Xu-Yan Wang, Yi-Hua Fan, Yu-Yan Li, Zhao Jiao, Xin-Ju Li*, Hua Jin, Jie Guo

Based on the Chinese medical canon to excavate the medicine law of yellowish leucorrhea disease

Xu-Yan Wang1, Yi-Hua Fan2, Yu-Yan Li1, Zhao Jiao1, Xin-Ju Li1*, Hua Jin1, Jie Guo3

1Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China;2The First Affiliated Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China; 3 The Second Affiliated Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin 300250, China.

In order to collect and analyze the literature on yellowish leucorrhea disease in, and to explore its treatment and medication law with data mining.Thewas used as the data retrieval source, and “Huangdai” (yellowish leucorrhea disease) and and other keywords were used as the keywords to do literature search. After excluding “gestational yellowish leucorrhea”, “jaundice and yellowish leucorrhea” and other diseases, the literature retrieval and data sorting and analysis were carried out, and the database was established by using Microsoft Excel 2010. Descriptive statistical method was used to analyze the nature, flavour, channel tropism and efficacy of medicine.Combined with the method in “the Research Platform for Inheritance of Traditional Chinese Medicine Academic Thoughts of Famous Gynecologists of Traditional Chinese Medicine”, the association rules between drugs were analyzed and their rules were excavated.Eighty-seven prescriptions, 152 traditional Chinese medicines, 20 core drug pairs, 39 common drug combinations and 5 core drug groups were collected and included.“Damp-Heat” is the fundamental pathological product of yellowish leucorrhea disease, and the basic treatments are “Releasing Heat” and “Eliminating Dampness”, “Regulating Liver Qi” and “Promoting Blood Circulation”, and “strengthening spleen” and stopping leucorrhea.

Literature mining, Yellowish leucorrhea disease, Medicine law,

1.includes many physicians formulas, these formulas are often many doctors’ clinical experience of crystallization for many years, worth learning from.

2. The core medicines for the treatment of yellowish leukorrhea are: Huangbo (), Huashi (), Huangqi (), Baizhu (), Fuling (), Chenpi (), Danggui (), Chuanxiong (), Chunpi (), Gancao ().

Background

Leucorrhea disease refers to the significant increase or decrease of leucorrhea amount, abnormal color, quality and odor [1]. Yellowish leucorrhea disease is a Chinese medical term and belongs to the category of leucorrhea disease. Bacterial vaginosis is an infection caused by the decrease of lactobacillus in the vagina and the increase ofand anaerobe [2]. Its clinical manifestations are increased vaginal secretions with a yellowish color, fishy smell, and vulva burning pain [1]. Therefore, the clinical treatment of bacterial vaginosis often refer to the yellowish leucorrhea disease of traditional Chinese medicine, from the dampness and heat treatment. Western medicine mostly uses metronidazole and other antibiotics to treat this disease, which has certain curative effect, but is easy to relapse and not easy to cure [3], and has some side effects [4]. By sorting out the literature on yellowish leucorrhea disease in the[5], the author uses modern data mining technology to analyze and summarize the treatment methods and medication rules of yellowish leucorrhea disease, so as to provide ideas for clinical treatment of yellowish leucorrhea disease and bacterial vaginitis.

Materials and methods

Prescription sources

(The 5th edition, Hunan Electronic Audio-visual Publishing House, the Key Electronic Publishing Planning Project of the Ninth Five-year Plan)

Search methods

The search term “Huangdai” (yellowish leucorrhea disease), “Daixiahuang” (yellowish leucorrhea disease), “Daixiahuanghou” (yellowish leucorrhea disease) were searched manually, and the source of thewas traced.

Information extraction standards

Inclusion criteria. (1) For the one that appears repeatedly in the articles, only one that is traced back to the earliest inclusion of the yellowish leucorrhea disease is selected. (2) In ancient books and documents, it is clearly written as yellowish leucorrhea prescription. (3) Include only one if the prescriptions have the same medicine but different dosage. (4) Include only one if the prescription and dose are the same but the prescription name is different. (5) Prescriptions including decoction, ointment, pill, powder and other dosage forms.

Exclusion criteria. (1) Special pathological yellowish leucorrhea disease: such as yellowish leucorrhea caused by summer-heat and dampness, yellowish leucorrhea during pregnancy, jaundice and leucorrhea, yellow and red leucorrhea, yellow leucorrhea during menstruation, yellow leucorrhea for the elderly, et al. (2) Non-drug means such as acupuncture, moxibustion, et al. (3) Provisions where is only a medical description but no definite prescription. (4) Recurrent provisions searched by multiple keywords. (5) Provisions where symptoms modified with keywords but not related with yellowish leucorrhea disease. (6) Provisions where is only prescription name but no medicine. (7) External use of traditional Chinese medicine.

Code standards. (1) The prescription name specification first refers to the[6]. If it is not entered in this book, that the most frequent names appear in the ancient books can be traced back. At the same time, reference to the(2015 edition) and the textbook of the 12th Five-Year Plan Traditional Chinese Medicine to carry out standardized records of relevant traditional Chinese medicines in the provisions. For example, Chuanpo () is standardized to Houpo (), Maozhu () is standardized to Cangzhu (), Haishi () is standardized to Haifushi (), and Chupi () is standardized to Chunpi (), et al.

Database establishment

By keyword search, 239 provisions were included in the original text, 112 provisions were included in the original text according to the standard, a total of 87 prescriptions and 152 herbs were included in the original text. A database was established by using Microsoft excel 2010, in which the composition of the drug was entered with a binary variable structure, that is, (0/1), the drug use was 1, and the unused drug was 0.

Data mining

The Apriori algorithm in the traditional Chinese medicine academic thought inheritance research platform was applied to analyze association rules between drugs [7]. Parameters were set to have a minimum support degree of 9% and a minimum confidence degree of 70%. The maximum number of the antecedent item is 5, among which the enhanced capacity ≥ 1, striving to explore the core drug law for the treatment of yellowish leucorrhea disease.

Results

Frequency of medication

Sorting by frequency counting from highest to bottom. The top 20 drugs of the use frequency were listed in Table 1, and the first 20 traditional Chinese medicines were classified into Table 2 and Table 3 according to the flavour classification and efficacy category. The target point of Huangbo () andis shown in Figure 1.

Law of formula

Use association rules to find out the correlation between hidden drugs in prescriptions. Using the platform’s algorithm to set the support level to 9% (representing be included in at least 9 prescriptions), the 20 core drug pairs (Table 4), 39 items of common drug combinations (Table 5), 5 items of core drug groups and their network display diagrams were obtained (see Table 6 and Figure 2).

Figure 1 Target point of Huangbo () and Chunpi ()

Table 1 Frequency of use of the top 20 medicines for yellowish leucorrhea disease

Table 1 Frequency of use of the top 20 medicines for yellowish leucorrhea disease (continued)

Table 2 The medicinal nature, flavor and channel tropism of yellowish leucorrhea disease

Table 3 Classification of drug efficacy in the treatment of yellowish leucorrhea disease

Figure 2 Core drug group network for yellowish leucorrhea disease

Table 4 Core drug pairs of treating yellowish leucorrhea disease

Table 5 Combination of common drugs for yellowish leucorrhea disease

Table 5 Combination of common drugs for yellowish leucorrhea disease (continued)

Table 6 Core drugs for yellowish leucorrhea disease

Discussion

Drug frequency analysis

In the, the most frequently used drugs for yellowish leucorrhea diseases are, Gancao (), Baishao (), Fuling (), Danggui (),, Baizhu (), Shanyao (), Cheqianzi (), Huashi (), Qianshi (), Banxia (),,, Ganjiang (), Chenpi (), Chuanxiong (), Qingdai(), Huanglian () and, et al. These drugs mainly have the function of “Clearing Heat” and “Removing Dampness”, “Nourishing Liver” and “Activating Blood”, “Invigorating Spleen” and “Stopping Dampness”. Among them,andremove dampness through diuresis,,,,invigorate spleen and clear dampness,,,,eliminate dampness,clear heat of liver,,,“Raise Liver” and “Activate Blood”,,“Tonify Spleen”,“Clear Heat” and “Dry Dampness”, stop the leucorrhea,clear away heat and detoxify, reconcile various drugs. Dampness is the key pathological factor of the leucorrhea, so there are many high frequency drugs to remove dampness. While yellow is a hot syndrome, therefore, the pathological factor of the yellow leucorrhea is dampness and heat, and the basic treatment method is to “Clear Heat” and “Remove Dampness”. Because the liver meridian passes through the genitals, and the yellow leucorrhea came out of the vagina, it can be seen that the basic pathogenesis of the yellow leucorrhea is related to the liver. And yellow is a hot syndrome, so useto “Clear Liver-Fire”,,,to “Nourish the Liver” and “Sooth the Liver” (it’s also called “Liver” regulation). “Spleen” deficiency cause the “Dampness”, so use,,,to “Invigorate Spleen and Remove Dampness”, useto “Tonify Spleen and Stop The Leucorrhea”.can be good to the “Lower-Jiao”, can “Clear Heat and Detoxify”, and can reconcile the drug, killing two birds with one stone.

These high frequency drugs are very close to the classic ancient prescription Yihuang decoction, Banxia Cangzhu decoction, Ermiao powder, Gancao Ganjiang Fuling Baizhu decoction, Erchen decoction and Xiaoyao powder. The classic ancient prescription Yihuang decoction comes from(a gynecological monograph by Fu Qingzhu in Qing Dynasty), is for the treatment of “women’s yellow leucorrhea like thick tea and smelling bad”, is the master of Fu Qingzhu in the treatment of yellow leucorrhea. Among the high frequency drugs,,,,are the composition of the classic ancient prescription Yihuang decoction, can “Clear Heat and Remove Dampness”, “Invigorate Spleen” and stop leucorrhea. The classic ancient prescription Banxia Cangzhu decoction is also used to treat “women’s yellow leucorrhea like yellow juice”, is also a special prescription for the treatment of yellow leucorrhea. Among the high frequency drugs,,,,,,,are all the composition of the classic ancient prescription Banxia Cangzhu decoction, can dry dampness and invigorate blood circulation.,is the composition of the classic ancient prescription Ermiao powder, it is a common prescription for the treatment of “Dampness” and “Heat” in the “Lower-Jiao”. The classic ancient prescription Gancao Ganjiang Fuling Baizhu decoction, coming from(a monograph on the treatment of internal injuries and miscellaneous diseases in Chinese medicine, written by Zhang Zhongjing at the end of the Eastern Han dynasty), is used for “Lower-Jiao” cold and dampness syndrome. As Zhang Zhongjing said “phlegm disease should be treated with warm drug”. Only warm drugs can “Melt the Dampness”. Although the yellow leucorrhea is caused by “Dampness-Heat”, it can complement each other by adding “Warm-Dry” and “Dampness-Removing” drugs based on the “Heat-Clearing” and “Dampness-Removing” drugs. Among the high frequency drugs,,,are the components of the classic ancient prescription Erchen decoction. Although the yellow leucorrhea is caused by “Dampness-Heat”, only “Clearing away Heat” and “Drying Dampness” will lead to cold and cold “Hurting the Spleen”, further “Aggravating Spleen Deficiency”. Therefore, add warm drugs to “Dry Dampness”, can achieve twice the result with half the effort. Among the high frequency drugs,,,,,are the composition of the classic ancient prescription Xiaoyao powder, having the function of nourishing blood and activating blood, “Invigorating Spleen” and “Removing Dampness”. Through the above prescription, it can be introduced from the side that the core pathogenesis of yellowish leucorrhea disease is “Dampness” and “Heat”. As in: “Because of the deficiency of “Spleen Qi”, the depression of “Liver Qi”, the invasion of “Moisture”, the force of “Heat”, it is bound to get the yellowish leucorrhea disease.”

Analysis of the nature, flavour and efficacy of drugs

According to Table 2, the drug flavor is mainly cold and warm, followed by calm and slight cold. The yellow leucorrhea is caused by “Dampness” and “Heat”, and only warm drug can “Melt the Dampness”, so the warm and cold drugs should be used together, work together to “Clear Heat and Dampness”. Dampness for a long time is easy to hurt “Spleen Qi”, so it is important to warm and benefit the “Spleen Qi”, but the overall medicine should be cold. The flavours are mainly bitter, sweet and pungent, as well as tasteless and astringent. Bitter can “Dry Dampness” and “Release Heat”; sweet can replenish energy and reconcile, can not only “Invigorate Spleen and Dehumidify”, but also reconcile various drugs, preventing “Heat”-clearing drugs being too cold to hurt the stomach. Pungent can disperse and go, can “Activate Qi” and promote blood circulation and “Remove Dampness”, preventing the stagnation of “Qi” and “Dampness”. The stagnation of blood forms water, activating blood is conducive to the formation of a virtuous cycle, dispelling dampness and turbidity. The channel tropism of core drugs are mainly spleen, lung, stomach and liver. It fits with the pathogenesis of “Liver Depression” and “Spleen Deficiency” and “Damp-Heat”.

As can be seen from Table 3, the highest frequency are “Heat-Clearing” drugs, “Deficiency-Tonifying” drugs, “Damp-Clearing” and diuresis-promoting drugs, astringent drugs, dehumidification drugs and so on. “Heat-Clearing” drugs mainly to “Clear Heat” and dry humidity, “Deficiency-Tonifying” drugs mainly “Nourish the Blood” and promote blood circulation, “Strengthen the Spleen” and “Replenish Qi”, astringent drugs mainly stop the leucorrhea, “Damp-Clearing” and diuresis-promoting drugs combined with dehumidification drugs strengthen the force of “Dispelling Dampness”. Therefore, “Clearing Heat” and “Removing Dampness” is the basic treatment of yellowish leucorrhea disease.

Analysis of core drug pairs

Based on the analysis of consequent drugs in core drug pairs, the most commonly used drugs are:,,,,,,. The drugs with higher association withare,,,, Geqiao (). The drugs with higher association withare, Renshen (), Chaihu (), Huangqi (). The drugs with higher association withis. The drugs with higher association withare,,. The drugs with higher association withare,,. The drugs with higher association withare,. The drugs with higher association withis. Through analysis of the consequent drug, its treatment method is basically consistent with the treatment of high frequency drugs mentioned above, that is, “Clearing Heat” and “Removing Dampness”, “Nourishing Liver” and “Activating Blood”. Among them,“Clear the Lower-Jiao Heat”,“Clear Away the Liver-Fire”,“Clear Away Heat” and “Detoxify”,“Eliminate Dampness”,“Remove Dampness” through diuresis,“Raise Liver” and “Activate Blood”,“Promote Qi” to “Activate Blood”. In the consequent term, the highest frequency of the core drug pair should be-.has a good effect on genital “Dampness” and “Heat”, andcan also “Clear Heat and Dampness” and stop leukorrhea, the compatibility of the two is the core combination of treatment. According to the analysis of 20 pairs of core drugs, these Chinese medicines are modified the classic ancient prescription Ermiao powder, Erchen decoction and Chaihu Shugan powder added and subtracted, have the effect of “Clearing Heat” and “Removing Dampness”, regulating “Liver Qi” and activating blood circulation, “Strengthening Spleen” and stopping leucorrhea, coincide with the overall efficacy of high frequency drugs. Therefore, “Damp Heat” is the important pathological factor of yellowish leucorrhea disease.

Analysis of commonly used drugs

According to the association rule chart of Table 5, the main treatment of yellowish leucorrhea disease is to “Clear Heat” and “Remove Dampness” and “Regulate Liver Qi”, “Nourish Blood” and “Invigorate Spleen”, among which the support degree of “Clearing Heat” and “Removing Dampness” is the highest. The highest degree of support are the combination of--,--,--.-belongs to Erchen decoction, which has the effect of eliminating dampness. And-is drug pair in the classic ancient prescription Biyu powder, has the function of “Clearing Heat and Dampness” and-can also “Invigorate Spleen” and “Remove Dampness”. It can be seen that the treatment of yellowish leucorrhea disease is mainly to “Clear Heat”, “Remove Dampness” and “Invigorate Spleen”, while “Regulating Liver Qi” and “Activating Blood Circulation” is auxiliary. The basic pathological factor of yellowish leucorrhea disease is “Dampness” and “Heat”, so remove “Dampness” from many angles is important.,,“Clear Heat” and “Dry Dampness”,,,,“Invigorate Spleen” and “Remove Dampness”,,,“Clear Away Heat” and promote diuresis,,,“Eliminate Dampness”,,“Invigorate Spleen” and “Invigorate Qi”, “Transport Dampness and Turbid”,“Clear Heat” and “Resolve Phlegm and Dampness”. Moreover, the genitals are the place where the “Liver Meridian” is followed, too much female thinking can easily lead to poor emotion, so the “Liver Qi Stagnation, Causing Phlegm and Dampness”. At the same time, “Liver Qi Stagnation” can cause “Spleen Qi Suppression”, forming a vicious cycle, so the addition of drug of regulating the “Liver” is important. For example,can “Clear the Liver and Fire”, can also detoxify,-can “Raise Liver” and “Activate Blood”,-“Soothe Liver” and “Activate Blood”,“Replenish the Liver” and “Remove Dampness”. “Dampness Stagnation” not only changes into “Heat” over time, but also leads to “Stagnation and Blood Stasis”, and female pelvic blood supply is poor, easy to stasis, so promote the circulation of “Qi” and blood by activating blood circulation, such as,. In addition to the above syndrome differentiation drugs, add,and so on to improve symptoms rapidly.

Analysis of core drug groups

The core drug groups in Table 6 are the classic ancient prescription Erchen decoction, Sijunzi decoction, Siwu decoction, and Biyu powder added and subtracted. Consequent mainly include,,,,, These drugs also have the effect of “Clearing Heat and Dampness”, “Invigorating Spleen” and “Activating Blood”, which coincides with the overall effect of high frequency drugs and core drugs. Among them,,,are closely related with, having the function of “Clearing Heat” and “Removing Dampness”. Whileis closely related with,, is the structure of the classic ancient prescription Sijunzi decoction;is closely compatible with,,, belonging to the framework of the classic ancient prescription Erchen decoction;is closely compatible with,,,, having the function of “Activating Blood Circulation and Clearing Dampness”;is closely compatible with,,,, having the function of “Invigorating the Circulation of Blood and Eliminating Dampness”. In addition, through these 5 core drug groups, it is found that each group has “Blood-Activating” drugs and “Dampness-Removing” drugs. It can be seen that “Promoting Blood Circulation and Dispelling Dampness” is an important treatment for yellowish leucorrhea disease.

Modern studies have shown thatcan promote the growth of lactobacillus vaginalis [8], regulate the imbalance of vaginal flora, repair the vaginal mucosa [9], moderately inhibitvaginalis, and have a good therapeutic effect on the yellowish leucorrhea disease [10].has the function of protecting vaginal mucosa [11].has obvious inhibitory effect on gardnerella vaginalis, and the curative effect is better than, Pugongying (), Kushen (), Baihuasheshecao () and other drugs [12].,,can improve immune ability and promote the growth of[13–17].has a strong anti-inflammatory and bactericidal effect, and has a good curative effect in the treatment of vaginitis [18].,can promotegrowth [19–20], andhas inhibitory effect onand other anaerobic bacteria [21]. Glycyrrhizic acid insignificantly increased the number of[22], at the same time,inhibits Gardner bacteria [23]. At present, pharmacological studies of,,and other drugs mainly concentrated in the intestinal flora, there are few studies on vaginal microflora, lacking evidence-based and high-quality clinical studies. In the following work, more work should be done to increase the pharmacological study of drugs on candida albicans, streptococcus and trichomonas, and other pathogenic bacteria and protozoa that cause vaginitis, so as to play a role in combination with clinical practice.

To sum up, dampness and heat are the basic pathological products of yellowish leucorrhea disease. The lesions involve the “Liver”, “Spleen” and “Kidney”, and the deficiency and excess inclusion is more common. The basic treatment is to “Clear Heat” and “Remove Dampness”, “Regulate Liver Qi” and promote blood circulation, and “Invigorate Spleen” and stop leucorrhea. The main prescriptions are: the classic ancient prescription Yihuang decoction, Banxia Cangzhu decoction, Ermiao powder, Gancao Ganjiang Fuling Baizhu decoction, Erchen decoction, Xiaoyao powder, etc. The core drugs are:,,,,,,,,,. In this paper, the Chinese medicine prescriptions fromon the treatment of yellowish leucorrhea disease were sorted and summarized, and the rule of drug use was analyzed, the purpose is to improve the clinical efficacy of Chinese medicine in the treatment of yellowish leucorrhea disease, make Chinese medicine in the compatibility of prescription more targeted. Most of the yellowish leucorrhea diseases can be used in the basic treatment of “Clearing Heat” and “Removing Dampness”, “Regulating Liver” and “Activating Blood”, “Invigorating Spleen” and stopping leucorrhea. It is the so-called “each disease has a specific prescription”, on the basis of closely linked to the basic pathogenesis of the disease, combined with syndrome differentiation and specific drugs, can be taken to a good curative effect [24].

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10.12032/MDM2020123001

Xin-Ju Li. Tianjin University of Traditional Chinese Medicine,Jinqin Garden A403, Jinghai District, Tianjin 301617, China. Email: mars402498971@126.com.

This study was supported by Tianjin Health and Family Planning Commission integrated Traditional Chinese and Western medicine research project (2017134).

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The authors declare that they have no conflict of interest.

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Xu-Yan Wang, Yi-Hua Fan, Yu-Yan Li, et al. Based on the Chinese medical canon to excavate the medicine law of yellowish leucorrhea disease. Medical Data Mining 2020, 3 (4): 141–151.

:Yu-Ping Shi.

:21 September 2020,

22 November 2020,

: 30 December 2020