Identification of core compositions of traditional Chinese medicine for Seborrhe

Meng-Xi Gao,Ai-Ying Zhang,Zhi-Dan Cao,Wei Fan,Tian-Tian Gai,Yan Wang

1Department of Graduate,Tianjin University of Traditional Chinese Medicine,Tianjin,China;

2School of nursing,Tianjin University of Traditional Chinese Medicine,Tianjin,China.

Abstract Objective:To explore the clinical medication rule of seborrheic dermatitis in modern Chinese medicine by data mining,in order to benefit the clinical treatment of seborrheic dermatitis in traditional Chinese medicine.Methods:From January 1,2010 to September 4,2019,articles on Chinese medicine for seborrheic dermatitis were searched systematically in CNKI,VIP and Wan Fang databases.Prescription databases were established through the Chinese Medicine Inheritance assistant system to mine and analyze the rules of data.Results:69 researches were screened out,72 prescriptions for seborrheic dermatitis.13 drugs were used more than or equal to 15 times,and 9 pairs of commonly used drugs with correlation coefficient above 0.045 were selected.Six core combinations and two new prescriptions were obtained.Conclusion:Data mining method was used to analyze the high-frequency drugs and drug pairs,which reflected the treatment principle of clearing heat and removing dampness,nourishing blood and moistening dryness,promoting qi and strengthening spleen in the clinical treatment of seborrheic dermatitis,and provided more intuitive research evidence for the follow-up clinical treatment.

Keywords:Seborrheic dermatitis,Medication rule,Traditional Chinese medicine,Data mining

Background

Seborrheic dermatitis is a chronic inflammation that often occurs in the rich parts of sebaceous glands such as the head,face,front,chest and back [1].It mainly presents clinical symptoms such as skin flushing,red skin lesions,white papules,greasy scales,and has varying degrees of pain or itching [2].Seborrheic dermatitis in traditional Chinese medicine (TCM)is named“Facial Traveling Wind”and“White Scrap Wind”because of its greasy skin,erythema and scales[3].“Surgery Zhenquan”records:“White debris wind in the first hair,extended to the face and ears itching,fly white debris over time,take off and regenerate.From muscle heat into the wind,wind evil into the pore,depression,blood dryness,skin dystrophy,dryness is also.

The morbidity of seborrheic dermatitis is 2%-5%.With the increasing pressure of modern society,the regularity of daily work and rest and the adjustment of dietary structure make the morbidity of seborrheic dermatitis increase year by year,and there is a trend of younger [4].At present,the main clinical treatment methods are oral antibiotics and external glucocorticoids [5].However,this chronic inflammation is prone to recurrence,and long-term treatment may lead to adverse reactions and decreased drug tolerance[6].Traditional Chinese medicine (TCM)has its unique advantages in the treatment of seborrheic dermatitis,and has achieved definite results in clinical practice in recent years.This study analyzed the literature of seborrheic dermatitis treated by modern Chinese medicine with the help of traditional Chinese Medicine Inheritance assistant system V2.5,in order to explore the law of clinical medication of modern Chinese medicine for seborrheic dermatitis,and provide a basis for follow-up research.

1 Materials and methods

1.1 Materials

Advanced retrieval method was used to search for seborrheic dermatitis,white dandruff wind,etc.The retrieval time was limited to 2010-01-01 to 2019-9-4.The retrieval databases were CNKI,VIP and Wanfang data journal paper resources.

1.2 Inclusion criteria

(1)There are complete prescriptions and medicines;(2)Establish clear observation group and control group;(3)Clinical research;(4)The medication method of traditional Chinese medicine is oral administration.

1.3 Exclusion criteria

(1)Summary;(2)Pharmacological study of a single Chinese herbal medicine;(3)Western medical method;(4)Medical case reports;(5)Experimental literature of animal models.

1.4 Data processing

The names of Chinese medicines and their processing specifications are unified according to the Pharmacopoeia of the People's Republic of China [7]and Chinese Medicine [8]of the 2015 edition.RadixRehmanniae Recens,dried rehmannia rootare unified asRadix Rehmanniae Recens,andPeriostracum Cicadae,Cicadaare unified asPeriostracum Cicadae.Pharmaceutical statistics did not include the addition or subtraction of Chinese prescriptions in the literature.Data were unified into EXCEL table to establish a database.

1.5 Data analysis

The frequency,prescription regularity,new prescription analysis and core drug combination of traditional Chinese medicine were analyzed by V2.5 software.

2 Results

2.1 Retrieval results

A total of 1169 relevant researches were retrieved and 69 were selected according to the inclusion,exclusion criteria of this study.A total of 72 effective prescriptions were obtained.

2.2 Frequency of medication

In this study,72 prescriptions for seborrheic dermatitis were collected,including 146 Chinese medicines.Drugs were ranked from high to low according to the frequency of occurrence.Among them,13 drugs were used more than 15 times in the prescription.Radix Glycyrrhizae,Radix Scutellariae,Radix Rehmanniae Recens,Cortex Moutan RadicisandCortex Dictamniwere the top five medicines (Table 1).

2.3 Formula analysis based on association rules

Sixty-nine Chinese medicine prescriptions for seborrheic dermatitis were analyzed.The number of supports was set to 14,which was equal to the number of prescriptions multiplied by the degree of support(20%)and the confidence was set to 0.6.That is to say,when the left side of symbolic drugs appeared,the probability of the right side of drugs was 60%.The regularity of common medicines used in modern Chinese medicine for seborrheic dermatitis and the association rules of drug combinations in prescriptions are obtained (Table 2 and Table 3).A network of association rules for drug combinations in prescriptions is shown in Figure 1.

2.4 Composition law analysis based on entropy clustering

Based on the pre-reading of data extracted from different parameters,the correlation degree was set to 5 and the penalty degree was set to 2.Cluster analysis was used to obtain the correlation degree between two drugs in 69 prescriptions for seborrheic dermatitis treated by modern Chinese medicine.Drugs with the interception correlation coefficient >0.045 were sorted according to the size of the correlation coefficient(Table 4).

2.5 Drug core combination analysis based on complex coefficient entropy clustering

Setting correlation degree 5 and penalty degree 2,the drug core combination analysis based on complex coefficient entropy clustering was carried out,and six groups of drug core combination were obtained (Table 5).

2.6 New Prescription Analysis Based on Unsupervised Entropy Hierarchical Clustering

Based on unsupervised entropy hierarchical clustering,three new drug combination are obtained on the basis of drug core.The new prescription is shown in Table 5.The network of new prescription drug combinations is shown in Figure 2.

3 Discussion

Seborrheic dermatitis early appeared in classics under the nicknames of“face travel wind”and“white chip wind”,such as“Surgical Dacheng Facial”[9]:“face travel wind,initial itching,next like ant line,face edema,more painful,caused by intense heat of YANG MING.”“Medical Emperor Jinjian-Key to Surgical Psychology”[10]said:“This syndrome was born on the face,the initial appearance of edema,itchy nymphs,dry skin,white debris,scratch after extremely itchy,scratch,hot and humid people immersed in yellow water;dry people blood,pain and embarrassment.By plain blood dryness,spicy taste,So Yang Ming stomach meridian is hot and humid.Ancient medicine [11]believed that the pathogenesis of this disease was mainly body heat,exogenous wind evil,depression and dryness,dampness and heat of the spleen and stomach,which hindered the skin,or body dryness,wind and heat,which caused the skin to lose its nourishment.Therefore,clinical [12]can be divided into wind-bloody dryness type,damp-heat accumulation type,stasis skin type and so on.The main treatment was liver-clearing and spleen-stomach fire.Clinical treatment should be based on clearing the Fu organs and detoxifying,relieving heat and dampness,dispelling wind and relieving itching,nourishing blood and moistening dryness.

Statistical analysis of prescriptions used in literature shows that there are 13 kinds of medicines in prescriptions for seborrheic dermatitis,which are more than or equal to 15 times.These 13 kinds of medicines can be divided into the following four categories.Radix Saposhnikoviae:Radix Scutellariae,Radix Rehmanniae Recens,Cortex Moutan Radicis,Cortex Dictamni,Radix Paeoniae Rubra,Radix Sophorae Flavescentis;formula for diuresis and diffusing dampness:Poria,Coix Semiciens;supplementing formula:Radix Glycyrrhizae,Radix Angelicae Sinensis,Rhizoma Atractylodis Macrocephalae;superficies-resolving formula:Radix Saposhnikoviae.Which explains the treatment principles of modern physicians in clearing away heat and dampness,cooling blood and moistening dryness,invigorating qi and invigorating spleen.

The top five drugs wereRadix Glycyrrhizae,Radix Scutellariae,Radix Rehmanniae Recens,Cortex Moutan RadicisandCortex Dictamni.Radix Glycyrrhizaeis sweet in taste,peaceful in nature,and belongs to the spleen and stomach meridian.It has the functions of invigorating the spleen,invigorating qi,clearing away heat,purging fire and detoxifying toxins.Radix Glycyrrhizaeis gentle and can be used to reconcile its medicinal properties.“Materia Medica Tongxuan”records“Radix Glycyrrhizae,the product of tranquillizing liver yang,enters the spleen and stomach alone.SoRadix Glycyrrhizaeis a mid-uterine tonic.”Drug Change Meaning”contains“Radix Glycyrrhizae,raw with cold and let out the fire.Except for the hot stomach.This is the power of cooling and eliminating heat.”Pharmacological studies have shown that [13]:Radix Glycyrrhizaealso has the effects of regulating immunity,anti-inflammation,anti-allergy,anti-bacterial and detoxification.Radix Scutellariaeis bitter and cold,and belongs to the lungs and spleen.It has the effect of clearing heat and drying dampness.The Book ofBenjing Fengyuanrecords thatRadix Scutellariaecan mainly treat dampness,relieve dampness and heat.Radix Scutellariae[14]Modern studies have shown that it has anti-viral,anti-bacterial and anti-inflammatory effects.Radix Rehmanniae Recensis sweet in taste and cold in nature.It belongs to the meridian of kidney.It has the functions of clearing heat and cooling blood,nourishing body fluid and nourishing yin.Radix Rehmanniae Recens[15]has been shown to have good antioxidant,anti-inflammatory and immunomodulatory effects.Cortex Moutan Radicisis bitter and slightly cold in nature.It belongs to the meridians of the heart,liver and kidney.It has the functions of clearing heat and cooling blood,promoting blood circulation and removing blood stasis.“Herbal of South Yunnan“records that theCortex Moutan Radiciscan remove the heat of blood fraction and has the effect of breaking blood and blood circulation.In recent years,studies [16]have found thatCortex Moutan Radicishas analgesic and anti-inflammatory effects,and can enhance the body's immunity.Cortex Dictamniis bitter in taste and cold in nature.It belongs to the meridians of the spleen,stomach and bladder.It has the functions of clearing heat,drying dampness,relieving itching and dispelling wind.”Compendium of Materia Medica”said:“Cortex Dictamni,cold and good,bitter and dry,belongs to the Foot -Taiyin,Yangming meridian can remove heat and humidity.At the same time,the results showed that [17]:Cortex Dictamnihad good anti-itching and anti-allergic effects.According to the more intuitive network chart,Radix Glycyrrhizae,Radix Scutellariae,Radix Rehmanniae Recens,Cortex Moutan Radicis,Cortex Dictamni and other drugs are closely related,and the five drugs are also the most frequently occurring.Drugs,in which Radix Scutellariae is located at the center of drug-related,can better reflect the importance of clearing away heat and dampness [18-20]in the treatment of seborrheic dermatitis.Based on the analysis of association rules,the commonly used drugs for seborrheic dermatitis were Radix Scutellariae and Cortex Moutan Radicis,followed by Radix Rehmanniae Recens and Radix Glycyrrhizae,Radix Rehmanniae Recens and Cortex Moutan Radicis.Radix Scutellariae is better than purging fire and detoxification,clearing heat and promoting qi;Cortex Moutan Radicis is better than clearing blood and heat,dispersing stasis and removing carbuncle;Radix Glycyrrhizae is better than invigorating spleen and harmonizing stomach qi,with moderate effect and the effect of various drugs.Radix Scutellariaecombined withCortex Moutan Radiciscan clear heat,detoxify,cool blood and disperse blood stasis.Radix Rehmanniae RecensandRadix Glycyrrhizaecan clear heat and nourish yin,harmonize spleen and stomach;Radix Rehmanniae RecensandCortex Moutan Radiciscan clear heat and cool blood,nourish yin and generating body fluid.

Table 1:Statistical results of traditional Chinese medicines with frequencies greater than or equal to 15

Table 2 Regularity of drug use patterns of common drugs based on association rules

Table 3 Rule analysis

Figure 1 Drug combination association rules network display (support 20%,confidence 0.6)

Table 4 Inter-drug association analysis based on improved mutual information method

Table 5 Core drug combinations in modern Chinese medicine prescriptions for seborrheic dermatitis

In this study,six potential core drug combinations were identified by entropy clustering method.Among them,Herba Hedyotishas bitter taste,sweet taste,cold temperament,stomach,large intestine and small intestine meridians.Its main function is to clear heat and relieve dampness.Clear heat and detoxify,eliminate carbuncles and dissipate silt,diffuse dampness.”Radix Salviae Miltiorrhizaeis bitter and slightly cold.It belongs to the heart and lung.Its function is to nourish blood circulation,remove blood stasis and soothe the mind.“Rihuazi Various Family Materia Medica”can be consulted as“nourishing the mind and resolving the mind,clearing up the customs.Break the hanging blood,replenish the new blood and so on.Fructus Crataegiis sour,sweet and mild in nature.It belongs to the spleen,stomach and liver.In“Renewal of Materia Medica”,there is a record of“treating dampness and heat due to spleen deficiency,eliminating food and abrasion,and facilitating stool and urine.”Herba Hedyotis,Radix Salviae MiltiorrhizaeandFructus Crataegiwere used together.It can be seen that the use of drugs of promoting blood circulation andpromoting water circulation and invigorating qi [21-22]and spleen [23-24]can not be ignored.

Table 6 New Prescriptions Based on Entropy Hierarchical Clustering

Figure 2 New network diagram of modern Chinese medicine for seborrheic dermatitis

Three new prescriptions have been found in this study.The first one isRadix Gentianae,Rhizoma Atractylodis Macrocephalae,Portulaca Herba,TalcumandFolium Isatidis.The five traditional Chinese herba have the effects of clearing away heat and dampness.The second new prescription isRadix Scutellariae,Semen Coicis,Cortex Moutan Radicis,Herba Hedyotis,Radix Salviae Miltiorrhizae,Fructus Craegi,among whichRadix Scutellariae,Herba Hedyotisare mainly heat-clearing,Cortex Moutan Radicis,Radix Salviae Miltiorrhizaehave the function of cooling blood,Semen Coicisis water-permeating and damp-invigorating the spleen,Fructus Crataegiis spleen-invigorating,qidispersing and stasis-dispersing,all medicines can be used together.In order to nourish blood,moisten dryness,diversify water and invigorate the spleen.The third new prescription isRadix Paeoniae Rubra,Rhizoma Alismatis,Gypsum Fibrosum,PoriaandCortex Magnoliae Officinalis.Radix Paeoniae Rubra,Gypsum Fibrosum,Cortex Magnoliae Officinaliscan clear away heat and dampness,Rhizoma Alismatis,Poriacan invigorate spleen,dry and diuresis,andRadix Paeoniae Rubra,Gypsum Fibrosum,Cortex Magnoliae Officinalis,Olae Officinalisnot only enhances the effect of clearing away heat and dampness,but also protects the spleen and stomach.The three new prescriptions all conform to the clinical dialectical classification of seborrheic dermatitis.

To sum up,this paper reveals the common medicines and drug pairs of traditional Chinese medicine in treating seborrheic dermatitis by data mining method.It summarizes the medication rules embodied in the literature of modern Chinese medicine in clinical treatment of seborrheic dermatitis,and provides a more objective new idea and method for the treatment of seborrheic dermatitis.The deficiency of this study lies in that the data obtained are obtained by software analysis,and more clinical evidence is needed.Moreover,this study only included Chinese literature,and lacked feedback on the treatment of seborrheic dermatitis in a wider range of traditional Chinese medicine.Therefore,in the future,we can consider the treatment of seborrheic dermatitis in a wider range of traditional Chinese medicine for basic research.