Analysis of the medication for impotence based on data mining

Ying Zhou, Jing-ming Zhang⋆

Shaanxi University of Chinese Medicine, Xianyang 712046, Shaanxi Province, China

Abstract Background: Impotence is a common disease of male reproductive system, western medicine treatment after drug withdrawal is prone to relapse, adverse reactions and other problems, while the treatment of impotence based on syndrome differentiation of traditional Chinese medicine can often get a satisfactory effect. Objective: To explore and analyze the law of drug use in treating impotence in the Dictionary of Traditional Chinese Medicine Prescriptions. Methods: The prescriptions for impotence in the Dictionary of Traditional Chinese Medicine Prescriptions were collected, the database was established by using Microsoft Excel, and the drug cluster analysis was conducted by using SPSS Statistics 21.0 software. Results: A total of 196 prescriptions were included, involving 305 traditional Chinese medicines. The frequently used drugs (excluding licorice) were Dodder, Cistanche, Prepared rehmannia root, Morinda officinalis, Polygala and Bidentate achyranthes in order. After statistical drug classification, the reinforcing deficiency drugs were the most frequently used. Conclusion: The law of drug use in treating impotence mainly includes reinforcing deficiency, inducing astringency and warming interior, while clearing heat and tranquilizing.

Key words: Impotence; Data mining; Law of drug use; Clinical application

Introduction

Impotence refers to penile erectile dysfunction and is a common disease of male reproductive system with the manifestations of with soft penis, weak erection, or short erection[1]. According to the cause, impotence can be classified into functional impotence and organic impotence. Clinically, functional impotence accounts for more than 90%, and organic impotence accounts for less than 10%. Phosphodiesterase inhibitor type 5 (PDE5i)is mostly used in modern medicine[2]. For example,sildenafil or tadalafil are first-line drugs for the treatment of impotence. However, once the drug is discontinued, the patient’s condition is recurrent. The treatment based on syndrome differentiation in the field of traditional Chinese medicine is an important method to recognize and treat impotence. In this study, Excel and SPSS software were used to sort, analyze and summarize the data, and further summarize the medication rules of impotence treatment by physicians in previous dynasties, aiming to provide new ideas for clinical new drug research and development.

Study Methods and Data

Prescription sources

Prescriptions were derived from the Dictionary of Traditional Chinese Medicine Prescriptions, using the search key words of “impotence”, “liver flaccidity”, “poor sexual activity”, “dysfunction of external genitals” and“non-erection”.

Inclusion Criteria

(1) The Dictionary of Traditional Chinese Medicine Prescriptions was searched for Chinese medical formula with the clear indications of “impotence”, “liver flaccidity”,“poor sexual activity”, “dysfunction of external genitals”and “non-erection”; (2) All the included prescriptions met the requirements of complete herbs, clear dosage and definite efficacy.

Exclusion Criteria

(1) Prescriptions for the treatment of organic impotence were excluded; (2) Simplex drug and external dressing were eliminated; (3) Prescriptions with different names and identical components were excluded. Finally, 196 prescriptions were retrieved.

Data processing

The data of relevant prescriptions, such as dynasty,prescription name, indication, dosage form, composition and efficacy, were used to establish the database of prescriptions for impotence treatment by using MicrosoftExcel. The statistical analysis was completed by two people, one was responsible for input and the other was responsible for proofreading to ensure the correct data.Subsequently, the core drugs were analyzed through the system clustering in SPSS Statistics 21.0.

Herb specification

According to the Chinese Materia Medica[3], the name of the drugs in the prescriptions was standardized, such as“Malaytea Scurfpea Fruit” and “Fruit of Malaytea Scurfpea”were standardized as “Psoraleae”, “Radix Astragali” was standardized as “Astragalus astragalus”. For drugs that were not recorded in Chinese Materia Medica, their names were standardized according to the Dictionary of Traditional Chinese Medicine[4], for example, “Dwarf Lilyturf Tuber”was standardized as “Ophiopogon Japonicus”, and “Yam”was standardized as “Dioscorea Opposita”.

Results

High-frequency drugs

According to the analysis of 196 included prescriptions,305 drugs were involved, and the cumulative frequency of drugs used was 2559. Table 1 shows the high frequency drugs and their proportion in the treatment of impotence.The most frequently used drugs were those for tonifying deficiency, which can be divided into tonifying qi,tonifying blood, tonifying Yin and tonifying Yang,among which, tonifying Yang had the highest frequency,and the results were shown in Table 3. Some drugs are adjusted appropriately according to their functions in the prescription. For example, frankincense is a kind of medicine for promoting blood circulation and removing blood stasis, but it has the effect of invigorating qi in the prescription, while Rhizoma anemarrhenae is a heat clearing medicine, but it has the effect of nourishing Yin in the prescription.

Table 1 High frequency drugs for treating impotence

High-frequency drugs

Through the analysis of the overall medication law for impotence, the frequency of each drug was counted, to find out the high-frequency drugs for analysis, analyze the medication trend of impotence treatment and find out the core drugs, in order to excavate the law of drug use.Among the 196 prescriptions, there were 22 drugs used for equal to or over 30 times, as shown in Table 2.

Table 2 Traditional Chinese drugs with a frequency of ≥ 30 times in the prescriptions for treating impotence

Table 3 Frequency of different types of tonifying deficiency herbs

Cluster analysis of drugs

The cluster analysis in SPSS Statistics 21.0 software was used to analyze the high-frequency drugs. The frequency was set as variables. The nearest neighbor elements were selected by the clustering method, and the measurement interval was parallel European distance. Cluster analysis was performed in a vertical direction, as shown in Table 4.After analysis, it was divided into 6 clusters, as shown in Table 5.

Table 4 Tree diagram of high-frequency drug cluster analysis

Table 5 High-frequency drug clustering table

Discussion

High-frequency drug analysis

Tonifying deficiency drugs with the highest frequency

In “Jingyue Quanshu · Impotence”, Doctor Zhang Jie-bin in Ming Dynasty has formally proposed the “impotence”name. In ancient times, most doctors have treated impotence on the basis of deficiency, and tonifying deficiency drugs can be divided into qi tonic, blood tonic,Yin tonic, Yang tonic. In “Plain Questions · Yin and Yang Classification of Natural Phenomena”, it states that the weakness of qi can cause impotence, qi belongs to Yang,the erection of the penis depends on the promotion and warming function of qi, insufficient qi results in the dysfunction of promotion and warming, the penis cannot erect, or insufficient qi fails to promote blood flow and make the penis malnutrition. The normal function of penis and testes depends on the filling of the blood, the erection of the penis, and the nutrition of blood. In “Ji Sheng Fang · Deficiency Treatment” written by Yan Yong-he, it describes the etiology and pathogenesis of erection failure caused by weakening of kidney Yang, such as deficiency of kidney Yang and weak warming are associated with penile erectile dysfunction. Zhang Jing-yue believes that in the treatment of impotence, single use of tonifying Yang components may cause kidney Yin injury, so an appropriate compatibility of tonifying Yang drugs with tonifying Yin drugs can make the interaction between Yin qi and Yang qi and produce the essential qi. Modern pharmacological studies have found that most of tonifying deficiency herbs can enhance the hypothalamic-pituitarygonadal axis function, dilate blood vessels, increase blood flow, improve sexual desire, and enable impotence patients to achieve and maintain sufficient erectile hardness[5-6].

Astringent drugs with the higher frequency

Astringent drugs mostly exert astringent effects and travel in the kidney meridian and bladder meridian, to secure essence, stop leukorrhagia and arrest polyuria. Some drugs are sweet and warm, which also reinforce the kidney. For the impotence with rapid onset, securing essence can prevent the outflow; for the impotence with slow onset,tonifying vital qi is necessary to cultivate the essence.Therefore, in the treatment of impotence, the appropriate addition of astringent drugs can improve the overall effect.

Warming interior drugs, clearing heat drugs and tranquilizing drugs with the average frequency

Warming interior drugs are mostly pungent-warm and strongly heat, a kind of traditional Chinese medicine whose main function is to warm the viscera, meridians and collaterals and eliminate interior cold. In the Ming Dynasty, Zhang Jie-bin believes that the impotence is“mostly caused by decline of vital gate fire, cold and deficiency in vital energy, or overexertion syndrome of seven emotions and injury of Yang qi”. In case of decline of vital gate fire, insufficient warmth, failure of penis erection, or cold coagulation in meridians, Yang qi cannot be transported to penis and testes, which is soft and disordered, so warming interior drugs are selected to warm interior and dissipate cold. Ye Tian-shi, a doctor in the Qing Dynasty, has proposed that, “dampness and heat are also the lesions, resulting in the failure of erection in penis and testes”. People are fond of eating fat and sweet foods, which is prone to produce dampness and heat and accordingly transfer downward to the penis and testes; poor sexual activity is possible related to the abuse of warm reinforcing products, which produce endogenous dampness and heat and accordingly transfer downward and coagulate in the lower Jiao, resulting in the dysfunction penis and testes, so clearing heat drugs are frequently used in impotence treatment[7]. In “ Plain Questions · Impotence”, it describes that the feelings and emotions may cause impotence. In modern society, the huge social competition has brought huge psychological pressure, excessive thinking, mental stress, leading to different degrees of physical and mental impairment, so appropriately compatible tranquilizing drugs can relieve qi depression[8].

High-frequency drug analysis

As shown in Table 3, the drugs with the frequency of greater than or equal to 64 times are Dodder, Cistanche,Prepared rehmannia root, Morinda officinalis, Polygala,and the root of Bidentate achyranthes. Dodder can tonify the kidney and nourish the essence, “De Pei Ben Cao” has recorded its “pungent, sweet, neutral flavor.and warm nature...used for penis cold”. In clinical practice, it is often used to treat infertility, polycystic ovary syndrome and other reproductive system diseases.Modern pharmacological studies have shown that dodder can improve kidney function and blood biochemistry in mice with kidney-Yang deficiency, so as to increase the proportion of sexual organs in mice with kidney-Yang deficiency[9]. Cistanche deserticola has the functions of tonifying kidney Yang, nourishing blood, moistening bowel and relieving constipation. “De Pei Ben Cao”has recorded its “salty flavor and warm nature, used for deficiency pain in the penis”. Modern pharmacological studies have found that the extract of Cistanche deserticola plays a positive role on the penis by reducing estradiol(E2) content and increasing gonadotropin (FSH) and testosterone (T) levels[10]. Prepared rehmannia root can nourish blood, nourish Yin, tonify essence and replenish marrow. It is recorded in Compendium of Materia Medica that “it can replenish bone marrow, generate muscle and blood, and repair the deficiency injuries of the five organs”. Rehmannia Glutinosa Polysaccharides of prepared rehmannia root can obviously improve the pathological changes of kidney[11]. Morindus officinalis is effective in tonifying kidney Yang and strengthening muscles and bones. Modern pharmacological studies have shown that moderate water extract of Morindus officinalis can improve sperm motility[12]. Polygala has mild nature, pungent and bitter flavor, and effects on tranquilizing, expelling phlegm, and relieving the swelling.Qin Guo-zheng[13]demonstrates that the impotence is caused by emotional changes to stimulate the dysfunction of penis, called “the depression-induced impotence”, the patients suffer from the penis dysfunction and maintain a negative and pessimistic emotion, called “the impotenceinduced depression”. Modern pharmacological studies show that polygala has an obvious anti-anxiety effect[14].In the Qing Dynasty, Chen Shi-duo has used Xuanzhi Decoction to tranquilize and replenish the kidney,send the clear to relieve the impotence. Polygala in this prescription can solve melancholy and pacify the mind.The root of Bidentate achyranthes has neutral nature,bitter and sour flavor, and effects on reinforcing the liver and kidney, strengthening muscles and bone, expelling stasis and dredging channels and collaterals. It is recorded in “Mingyi Bielu” that “it has sour flavor, neutral nature,and non-toxic. It is mainly used to treat male Yin diabetes, to strengthen the energy and replenish the bone marrow”. Modern pharmacological studies have shown that 14-acetyltalatisamine achyranthan from Bidentate achyranthes has a protective effect against oxidative stress injury of the kidney[15].

High-frequency drug cluster analysis

According to cluster analysis, six clustering formulas can be obtained and analyzed in combination with the law of drug use. Class 1 formula includes Dodder and Cistanche

Deserticola, dodder can tonify kidney essence, Cistanche Deserticola can tonify kidney Yang and blood, the combination of two drugs can tonify kidney and replenish essence; Class II formula includes Fructus Lycii, Cornus Officinalis and Cornu Cervi Pantotrichum. Fructus Lycii nourishes liver and kidney, relieving desertion with astringents, Cornu Cervi Pantotrichum strengthens kidney Yang and benefits essence and blood, the combination of three drugs can nourish and replenish the liver and kidney. Cluster III formula includes Poria Cocos, Fructus Cnidii, Angelica sinensis, Chinese yam, Fructus Psoraleae and Ginseng, Poria Cocos can strengthen spleen and calm heart, Fructus Cnidii can warm kidney and invigorate Yang, Angelica sinensis can nourish blood and promote cirvulation, Chinese yam can tonify kidney and have astringent effect, Fructus Psoraleae can warm kidney and invigorate Yang, Ginseng can tonify spleen and invigorate qi, the combination can invigorate heart and spleen, tonify kidney and consolidate essence. Cluster IV formula includes Dipsacus Asper, Cinnamomum Cassia and Eugenia Caryophyllata. Dipsacus Asper can tonify the kidney Yang, Cinnamomum Cassia can tonify the fire and assist the Yang, Eugenia Caryophyllata can tonify the kidney and assist the Yang, the combination of three drugs can warm the kidney and assist the Yang. Cluster V formula includes Foeniculum Vulgare and Atractylodes Macrocephala, Foeniculum Vulgare can disperse cold to regulate qi, Atractylodes Macrocephala can strengthen spleen and invigorate Qi, the combination of two drugs can invigorate qi and rise Yang, in treatment of impotence caused by unrising of lucid Yang. Cluster VI formula includes Eucommia ulmoides, Radix Aconiti lateralis,Bidentate achyranthes, Radix morindae officinalis, Radix Polygalae and Prepared rehmannia root, Eucommia ulmoides can reinforce the liver and kidney, Radix Aconiti lateralis can tonify fire and assist Yang, Bidentate achyranthes can reinforce the liver and kidney, Radix morindae officinalis can reinforce the kidney and assist Yang, Radix Polygalae can tranquilize, Prepared rehmannia root can replenish essence, the combination of six drugs can warm reinforce the liver and kidney, replenish essence and bone marrow.

In summary, through the data mining of prescriptions for treating impotence in the Dictionary of Traditional Chinese Medicine Prescriptions, it is preliminarily concluded that the law of drugs use in impotence treatment is as follows: The Chinese herbal drugs used for the treatment of impotence are tonifying deficiency drugs,astringent drugs, warming interior drugs, clearing heat drugs, and tranquilizing drugs. Among them, tonifying Yang drugs is the most frequently used medicine for tonifying deficiency, so it can be concluded that Yang deficiency is the most important cause of impotence.High-frequency drugs used in treatment of impotence are Dodder, Cistanche, Prepared rehmannia root,Morinda officinalis, Polygala and Bidentate achyranthes in order. High-frequency drugs enter the liver and kidney meridians, reflecting the characteristics of the homogeny of liver and kidney, the liver reserves the blood and the kidney reserves the essence, mutual transformation between blood and essence produces the concept of the homology, so the impotence is mostly associated with the liver and kidney. However, this study includes a small number of prescriptions, and no modern prescription for the treatment of impotence is used, furthermore only a clustering analysis on the retrieved data is performed,no correlation analysis is carried out on the relationship between drugs, which indicate some limitations. The conclusion cannot fully reflect the law of drug use in treatment of impotence, therefore, future researches are required to expand the scope of data retrieval and perform a correlation analysis for a more comprehensive analysis of the drugs.