Prescription Patterns of Traditional Chinese Medicine for Peptic Ulcer Disease in Taiwan: A Nationwide Population-based Study
Authors
Chin-Ying Huang, M.D.1,2*, Wan-Yu Lai, M.D.3,4*, Mao-Feng Sun, M.D.,Ph.D.2,5,6, Che-Chen Lin, M.S.7, Bor-Chyuan Chen, M.D.,M.S.8, Hong-Jen Lin M.D.,Ph.D.2,9, Chung-Hsien Yang M.D.,M.S.2,9, Kuo-Chin Huang, M.D.,M.S. 2,6, Hung-Rong Yen, M.D., Ph.D. 1,2,5,6
*These authors contributed equally as co-first authors. Affiliations
1Research Center for Traditional Chinese Medicine, Department of Medical Research, China Medical University Hospital, Taichung, Taiwan
2Department of Chinese Medicine, China Medical University Hospital, Taichung, Taiwan 3Department of Traditional Chinese Medicine, Center for Traditional Chinese Medicine, Chang Gung Memorial Hospital, Taoyuan, Taiwan
4School of Traditional Chinese Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan
5Research Center for Chinese Medicine & Acupuncture, China Medical University, Taichung, Taiwan
6School of Chinese Medicine, China Medical University, Taichung, Taiwan
7Health Data Management Office, China Medical University Hospital, Taichung, Taiwan 8Department of Chinese Medicine, Buddhist Dalin Tzu Chi General Hospital, Chiayi, Taiwan.
9School of Post-Baccalaureate Chinese Medicine, China Medical University, Taichung, Taiwan
Corresponding author: Hung-Rong Yen, M.D., Ph.D.
Research Center for Traditional Chinese Medicine, Department of Medical Research, and Department of Chinese Medicine, China Medical University Hospital
2 Yude Road, North District, Taichung 404, Taiwan. Office: +886-4-2205-2121, ext. 1672
Fax: +886-4-2236-5141
Abstract
Ethnopharmacological relevance. Peptic ulcer disease is a common digestive disease. Although current treatment combined with antibiotics is effective, concerns about antibiotic resistance or other adverse effects have been raised. Furthermore, there is a lack of large-scale survey on the use of traditional Chinese medicine (TCM) for the treatment of peptic ulcer disease. This study aimed to investigate the utilization of TCM for the treatment of peptic ulcer disease in Taiwan.
Materials and methods. We analyzed a random sample comprised of one million individuals with newly diagnosed peptic ulcer disease between 2001 to 2010 from the National Health Insurance Research Database in Taiwan. Demographic characteristics, TCM usage, the frequency as well as average daily dose of Chinese herbal formulas and the single herbs prescribed for patients with peptic ulcer disease, were analyzed.
Results. A total of 96,624 newly diagnosed subjects with peptic ulcer disease were included. 14,983 (15.5%) patients were TCM users. People residing in highly urbanized areas, younger people and female (compared with male) were more likely to use TCM. With regard to the comorbidities, TCM users had a lower prevalence of coronary artery disease, chronic obstructive lung disease, diabetes mellitus and liver cirrhosis and stroke. The average time between onset of peptic ulcer disease and the first visit to a TCM clinic was 4.7 months. Majority of the patients (n=14,449; 96.4%) received only Chinese herbal remedies. The most frequently prescribed Chinese herbal formula and single herb was Ban-Xia-Xie-Xin-Tang (Pinelliae Decoction to Drain the Epigastrium) and Hai-Piao-Xiao (Os Sepiae), respectivley. The core pattern analysis showed that combination of Ban-Xia-Xie-Xin-Tang, Hai-Piao-Xiao (Os Sepiae), Yan-Hu-Suo (Rhizoma Corydalis), Bei-Mu (Bulbus Fritillariae Thunbergii) and Chuan-Lian-Zi (Fructus Toosendan) was most frequently used for peptic ulcer disease.
Conclusions. Our study identified the core prescription patterns of TCM for patients with peptic ulcer disease in Taiwan. Further basic and clinical studies are necessary to elucidate the efficacy and mechanisms.
Keywords: Ban-Xia-Xie-Xin-Tang; complementary and alternative medicine; national health insurance research database; Os Sepiae; peptic ulcer disease; traditional Chinese medicine.
1. Introduction
Peptic ulcer disease is a common digestive disorder, including gastric and duodenal ulcers. In the United States, approximately 15 million people have peptic ulcer disease (Torpy et al., 2012). About 12% of males and 10% of females suffered from peptic ulcer disease over their lifetimes (Wang et al., 2012). It’s an imbalance of aggressive gastric luminal factors and defensive mucosal barrier function. Helicobacter pylori infection significantly contributed to 60% to 80% of gastric ulcers and 70% to 90% of duodenal ulcers (Hildreth et al., 2008). Disruption of mucosal barrier by non-steroid anti-inflammatory drugs (NSAIDs) and aspirin is also an important cause of peptic ulcer disease (Malfertheiner et al., 2009). The most common clinical manifestation of peptic ulcer disease is epigastric pain (Barkun and Leontiadis, 2010). Upper gastro-intestinal bleeding is one of the most severe and frequent complications of peptic ulcer disease. (Lu et al., 2004).
Conventional Western medications for the treatment of peptic ulcer disease include antacids, anti-secretory medications such as H2-receptor antagonists and proton-pump inhibitors. Ever since the discovery of the relationship between Helicobacter pylori and peptic ulcer disease, an antibiotics regimen targeting eradication of Helicobacter pylori has become the mainstream therapy for peptic ulcer disease. Although triple or quadruple therapy has been developed for the eradication of Helicobacter pylori (Luther et al., 2010), increasing antibiotic resistance and intolerance has made alternative treatments necessary (Malfertheiner et al., 2011). The use of antibiotics also has an unknown effect on the homeostasis of gut microbiome (Malnick et al., 2014). Other side effects resulting from the conventional medications include constipation and diarrhea (Cohen et al., 2015), impotence (Sabesin, 1993), interference with drug metabolism (Pattichis and Louca, 1995) and parietal cell hypertrophy (Ksiadzyna et al., 2015). These unwanted side effects drive some patients to seek alternative advice. It is necessary to investigate the usage of traditional medicine for the treatment of peptic ulcer disease.
Previous study of traditional Chinese medicine (TCM) have found that Si-Jun-Zi-Tang can inhibit the hypersecretion of hydrogen chloride in the stomach in a rate model of
stress-induced peptic ulcers (Chen et al., 2013). Chai-Hu-Gui-Zhi-Tang and can prevent the recurrence of peptic ulcers (Chen et al., 2010) and another formula HZJW can heal peptic ulcer and inhibit Helicobacter pylori (Xie et al., 2013). Unfortunately, evidence obtained from high-quality clinical studies is very limited (Zhou et al., 2007). Due to the lack of knowledge about the prescription profile of TCM, researchers and doctors have found it difficult to select optimal candidates to explore the potential efficacy and mechanisms of Chinese herbal products targeting peptic ulcer disease.
TCM, which includes acupuncture and moxibustion, Chinese traumatology and Chinese herbal products, has been integrated as an important part of healthcare in Taiwan. It has been used in various diseases such as gynecologic disease (Yen et al., 2015a), atopic dermatitis (Lin et al., 2014), rhinitis (Yen et al., 2015b; Yen et al., 2015c), asthma (Huang et al., 2013) and endocrinologic disorder (Hsu et al., 2014; Yu et al., 2014). The Taiwanese National Health Insurance program, which was established in 1995, also reimburses the above-mentioned TCM services (Huang et al., 2014; Yen et al., 2013). This mandatory insurance program covers approximately 23 million people, comprising 99.89% of the total population in 2010 (BoNH, 2010). Claims data from the National Health Insurance program were de-identified and sent to the National Health Research Institutes to form the National Health Insurance Research Database (NHIRD). This database provides a nationwide population-based claims database with long-term follow-up. The aim of this study is to analyze this comprehensive database and to determine the TCM utilization patterns of newly diagnosed peptic ulcer disease patients in Taiwan. The results of this study should provide valuable information for further pharmacological studies and clinical trials.
2. Materials and Methods 2.1. Data Source
This study was designed as a population-based study analyzing a sample of one million subjects randomly selected from the 23 million beneficiaries of the National Health Insurance program in Taiwan. The identification numbers of all individuals were
encrypted and transformed to protect the privacy of enrollees. There was no significant difference between the randomly selected sample and the original NHIRD (http://nhird.nhri.org.tw/en/Data_Subsets.html). The datasets contain patient’s gender and date of birth, all records of clinical visits and hospitalization, prescribed drugs and dosages, including Chinese herbal products, and the major diagnoses coded in the International Classification of Diseases, Ninth Revision, and Clinical Modification (ICD-9-CM) formats. This study was approved by the Research Ethics Committee of the China Medical University and Hospital (CMU-REC-101-012).
2.2. Study Subjects
The selection of study subjects from the random sample of one million individuals was represented as Figure 1. Of the one million randomly selected individuals in the National Heath Insurance Program, we identified 176,300 patients with peptic ulcer disease (ICD-9-CM code: 531-534). Prevalent cases (� =79,676) that had been diagnosed before the end of 2000 were excluded to ensure that all the subjects included were newly diagnosed. Finally, 96,624 study subjects diagnosed as peptic ulcer disease from 2001 to 2008 were included in the study cohort with a follow-up period through 2010. They were further divided into TCM users (n=14,983) and non-TCM users (n=81,641). TCM users were defined as those who visited TCM clinics. Non-TCM users were defined as those who never visited TCM clinics after the initial diagnosis of peptic ulcer disease.
2.3.Study Variables
To determine the key independent variables for utilization of TCM among peptic ulcer disease patients, we selected a series of demographic factors based on previous studies (Huang et al., 2014; Yen et al., 2013). The subjects were categorized into three groups according to age: <20, 20-39, 45-59, and ≥60 years. Urbanization levels in Taiwan are divided into four levels as previous described (Yen et al., 2015c). Level 1 indicates the “most urbanized” communities and level 4 indicates the “least urbanized” communities. We also searched the NHIRD database for clinical comorbidities and treatment records related to peptic ulcer disease as independent variables. The comorbidities were identified by ICD-9-CM codes, including 410-414 (coronary artery disease; CAD), 496 (chronic obstructive lung disease; COPD), 250 (diabetes mellitus; DM), 571 (liver cirrhosis) and stroke (430-438).
Data analysis consisted of descriptive statistics, including the prescription rates of TCM users stratified by patient’s demographic characteristics, indications for the prescription of TCM, and the most frequently prescribed Chinese herbal products used when treating peptic ulcer disease. The data were analyzed using SAS software, version 9.2 (SAS Institute Inc., Cary, NC, U.S.A.). Univariate analysis was utilized to compare the TCM users with the non-TCM users. Pearson’s χ2 tests was performed to assess the relationship between the categorical variables and to examine the differences between TCM users and non-TCM users. A P-value <0.05 was considered statistically significant. Analysis of core prescription patterns was described previously (Chang et al., 2015). In brief, an open-sourced freeware NodeXL (http://nodexl.codeplex.com/) was used to identify the core patterns of Chinese herb products for the treatment of RA patients, and the most common two herbal combinations were applied in this network analysis. The thicker line width, defined as counts of connections between formulas and herbs, indicated significant prescription patterns in the network.
3. Results
There were 96,624 patients who were newly diagnosed with peptic ulcer disease. Among them, 14,983 (15.5%) patients used TCM outpatient services for the treatment of peptic ulcer disease at least once. The mean age of TCM users was younger than that of non-TCM users (40.3 versus 50.5 years old). Majority (59.7%) of the TCM users were female. Most of the TCM users resided in urbanized areas. With regard to the comorbidities, TCM users had a lower prevalence of coronary artery disease, chronic obstructive lung disease, diabetes mellitus and liver cirrhosis and stroke. The average time between onset of peptic ulcer disease and the first visit to a TCM clinic was 4.7 months (Table 1).
Table 1. Demographic characteristics of TCM and non-TCM users among patients with peptic ulcer disease from 2001 to 2010 in Taiwan
Variable Non-TCM users N (%) TCM users N (%) p value No of subjects 81641 (84.5) 14983 (15.5) <0.0001 Age at baseline, mean years (SD)* 50.5 (17.7) 40.3 (16.5) <0.0001
Table 1. Demographic characteristics of TCM and non-TCM users among patients with peptic ulcer disease from 2001 to 2010 in Taiwan
Variable Non-TCM users N (%) TCM users N (%) p value 20-39 20218 (24.8) 6064 (40.5) 40-59 32445 (39.7) 5408 (36.1) ≧60 25731 (31.5) 1951 (13.0) Sex Female 40462 (49.6) 8941 (59.7) <0.0001 Male 41179 (50.4) 6042 (40.3) Urbanization 1 (highest) 22559 (27.6) 4074 (27.2) <0.0001 2 23615 (28.9) 4576 (30.5) 3 14352 (17.6) 2982 (19.9) 4+ (lowest) 21114 (25.9) 3351 (22.4) Comorbidity CAD 14286 (17.5) 1213 (8.1) <0.0001 COPD 3259 (4.0) 164 (1.1) <0.0001 DM 8807 (10.8) 626 (4.2) <0.0001 Stroke 3668 (4.5) 187 (1.2) <0.0001 Liver cirrhosis 16484 (20.2) 2241 (15.0) <0.0001 The duration between onset of peptic
ulcer disease and the first visit to a TCM clinic, month
4.7 * t-test.
TCM: traditional Chinese medicine; CAD: coronary artery disease; COPD: chronic obstructive lung disease; DM: diabetes mellitus.
Regarding the treatment modalities given to patients with peptic ulcer disease, 14,449 (96.4%) patients received only Chinese herbal remedies, while 277 (1.9%) patients were treated by acupuncture or Chinese traumatology only and 257 (1.7%) patients received combination of both treatments. More than half of the patients (n=8327; 55.6%) visited TCM clinics for 1-3 times and 3719 (24.8%) patients visited TCM clinics for more than 6 times (Table 2).
Table 2. Frequency distribution of TCM clinic visits and treatment modalities among TCM users from 2001 to 2010 in Taiwan
Number of TCM clinic visits Chinese herbal remedies only N (%) Acupuncture or Chinese traumatology N (%) Combination of both treatments N (%) Total of TCM clinic visits N (%) All 14,449 (96.4%) 277 (1.9%) 257 (1.7%) 14,983 (100%)
1-3 7838 (54.2) 250 (90.3) 239 (93) 8327 (55.6)
4-6 2916 (20.2) 17 (6.1) 4 (1.6) 2937 (19.6)
>6 3695 (25.6) 10 (3.6) 14 (5.4) 3719 (24.8)
TCM: traditional Chinese medicine
To investigate the prescription patterns of the Chinese herbal remedies, we conducted a comprehensive analysis and identified ten most commonly prescribed Chinese herbal formulas and single herbs, respectively. The most frequently prescribed Chinese herbal formula was Ban-Xia-Xie-Xin-Tang (Pinelliae Decoction to Drain the Epigastrium) (Table 3).
Table 3. Ten most common herbal formulas for patients with peptic ulcer diseases from 2001 to 2010 in Taiwan.
Herbal formula English name
Number of person-days N = 2050,356 (%) Average daily
dose (g)Indications in TCM use
Ban-Xia-Xie-Xin-Tang Pinelliae Decoction to Drain the Epigastrium 173,041 (8.4) 6.5
epigastric focal distention, fullness and tightness with very slight or no pain, dry heaves, vomiting, borborygmus Xiang-Sha-Liu-Jun-Zi-Tang Six Gentlemen Decoction with Aucklandia and Amomum 119,886 (5.8) 5.8
nausea and vomiting, emaciation, anorexia with a full feeling after very little food, weak abdomen
Ping-Wei-San CalmStomach Powderthe104,913 (5.1) 5.1
distention and fullness in epigastrium and abdomen, loss of taste and appetite, heavy sensation in the limbs and body
An-Zhong-San Calm the MiddlePowder 77,668 (3.8) 6.2 neurogenic gastric pain, ulcer, overabundance of stomach acid Jia-Wei-Xiao-Yao-San AugmentedRambling
Powder
68,619
(3.3) 5.7
Irritability, short temper, restlessness, fever or tidal fever, dry mouth, lower abdominal pain Huo-Xiang-Zheng-Qi-Tang Agastache Powder to Rectify the Qi 46,038 (2.2) 4.8
fever and chills, headache, abdominal fullness and oppression, pain, nausea and vomiting, borborygmus, diarrhea, loss of taste, aversion to cold
Shen-Ling-Bai-Zhu-San Ginseng, Poria and Atractylodis Macrocephalae Powder 43,715 (2.1) 6.3
loose stools or diarrhea, weak extremities, weight loss, distention and a stifling sensation in abdomen, pale wan, indigestion
Ma-Zi-Ren-Wan Hemp Seed Pill 43,433 (2.1) 2.4
constipation with hard, difficult to expel stool, dry skin, hemorrhoids, nocturia, dizziness Si-Ni-San Frigid Extremities Powder 40,197 (2.0) 5.2
cold extremities with heat in the interior, irregular fever, fullness and distention, abdominal pain, severe diarrhea, dysentery
Bao-He-Wan PreserveHarmony Pill 35,829 (1.7) 5.8
distention and fullness in abdomen, abdominal distention with occasional pain, rotten smelling belching, acid regurgitation, nausea and vomiting, aversion to food
Regarding the single herbs for the treatment of peptic ulcer disease, Hai-Piao-Xiao (Os Sepiae) was the most frequently prescribed single herb (Table 4).
Table 4. Ten most common single herbs for patients with peptic ulcer disease from 2001 to 2010 in Taiwan Single herbs Number of person-days N = 2565,558 (%) Average daily dose (g)
Indications in traditional Chinese medicine
Hai-Piao-Xiao
Os Sepiae seu
Sepiellae 119,120 (4.6) 1.7
stomach acidity with stomach or epigastric pain, distasteful belching or acid regurgitation,
bleeding Yan-Hu-Suo RhizomaCorydalis 96,337 (3.8) 1.6
pain affecting the chest, abdomen or limbs, epigastric pain and dysmenorrhea
Bai-Ji RhizomaBletillae 75,750 (3.0) 2.3
bleeding from the lungs and stomach with hematemesis, hemoptysis and epistaxis
Bei-Mu Bulbus Fritillariae
Thunbergii 66,378 (2.6) 1.9
neutralize acid, chronic cough, slight sputum
Da-Huang RadixRhizoma Rheiet55,338 (2.2) 0.7 constipation,distention and pain abdominal Hou-Po
Cortex Magnoliae
Officinalis 52,408 (2.0) 1.4
abdominal distention and fullness, nausea, and diarrhea
Dan-Shen Radix SalviaeMiltiorrhizae 45,621 (1.8) 1.3 abdominal pain, rib andhypochondriac pain Mu-Xiang Radix
Aucklandiae 45,046 (1.8) 1.2
anorexia, a feeling of food sitting in the stomach, epigastric or abdominal pain or distention, nausea and vomiting
Chuan-Lian-Zi
Fructus
Toosendan 38,223 (1.5) 1.1
distention and pain and bulging disorders
Sha-Ren FructusAmomi 37,637 (1.5) 1.1
distention and pain, in the epigastrium and abdomen, anorexia, vomiting and diarrhea
The top 100 herbal formulas and single herbs for peptic ulcer patients were analyzed through open-sourced freeware NodeXL, and the core pattern of the prescriptions was the combination of Ban-Xia-Xie-Xin-Tang, Hai-Piao-Xiao (Os Sepiae), Yan-Hu-Suo (Rhizoma Corydalis), Bei-Mu (Bulbus Fritillariae Thunbergii) and Chuan-Lian-Zi (Fructus Toosendan) (Figure 2).
4. Discussion
This nationwide population-based study investigated the utilization of Chinese herbal products prescribed by licensed TCM doctors for patients who were newly diagnosed with peptic ulcer disease. We found approximately 15.5 percent of the patients visited TCM clinics. Ban-Xia-Xie-Xin-Tang （ Pinelliae Decoction to Drain the Epigastrium）and Hai-Piao-Xiao (Os Sepiae) were the most commonly prescribed herbal formula and single herb, respectively. This is so far the largest comprehensive analysis of TCM usage among patients with peptic ulcer. The results from this study can be used for further pharmacological investigation or clinical trials.
In accordance with previous findings (Shih et al., 2012; Shih et al., 2009; Yen et al., 2013), we found that younger people, women (compared with men), and people living in higher urbanized areas were more likely to visit TCM than non-TCM users. Although sometimes TCM users had self-reported poor health status tended to use TCM services (Shih et al., 2009), we found that TCM users among peptic ulcer patients had a lower prevalence of comorbidities.
In this study, patients visited TCM services 4.7 months after initial diagnosis of peptic ulcer. The current Western medical treatment for peptic ulcer disease includes an antibiotics regimen targeting eradication of Helicobacter pylori (Luther et al., 2010). Some patients who believe in TCM or cannot tolerate the side effects of this regimen might seek TCM help after the initial diagnosis (Malfertheiner et al., 2011). In consistency with other studies in gastrointestinal disease or internal diseases, herbal remedies are the most common treatment approaches. (Huang et al., 2013; Pasalar and Lankarani, 2015; Yen et al., 2015b). We found that only very few patients received acupuncture therapy.
Ban-Xia-Xie-Xin-Tang was the most frequently prescribed formula for peptic ulcer. It was originally documented in an ancient literature “Shang Han Lun”. In an animal study, Ban-Xia-Xie-Xin-Tang reduced 70.1% of the ulcer areas in mice, while its derivative formula could even inhibited 96.9% ulcers (Xue et al., 2011). Another animal study
conducted in Japan also observed that pretreatment with Ban-Xia-Xie-Xin-Tang could markedly inhibit the reduction of gastric mucin content and the development of gastric ulcers (Li et al., 1998). In human study, a meta-analysis including ten randomized controlled trails with a total of 972 patients showed that Ban-Xia-Xie-Xin-Tang had a better effect than Western medicine in treating functional dyspepsia, consisting of epigastric pain, burning, fullness, discomfort, early satiety, nausea, vomiting, and belching (Gan et al., 2014). Intra-gastric administration of Ban-Xia-Xie-Xin-Tang extracts could lead to decreased mRNA expression levels of IL-5 and IL-13 in the colonic tissue (Wang et al., 2014a). In addition, Ban-Xia-Xie-Xin-Tang suppressed TNF-α, IL-1β, IL-17, IL-23 and COX-2 production in a dextran sulfate sodium (DSS)-induced chronic ulcerative colitis model (Chen et al., 2015).
The second commonly prescribed herbal formula is Xiang-Sha-Liu-Jun-Zi-Tang, which has long been used to treat gastrointestinal discomfort in clinical practice. In a recent study, it was reported to increase the secretion of plasma motilin, lower serum gastrin levels, and enhance smooth muscle contraction by increasing calcium levels (Tian et al., 2014). In addition, it can improve electrogastrogram, promote gastrointestinal motility and gastric emptying, decrease gastric sensitivity, and regulate gastrointestinal hormone (Feng, 1992). A meta-analysis found that Xiang-Sha-Liu-Jun-Zi-Tang could significantly improve symptoms better than prokinetic drugs for patients suffering from functional dyspepsia (Xiao et al., 2012). Its derivative, Si-Jun-Zi-Tang, has been reported to inhibit stress-induced ulcer by reducing the hypersecretion of hydrogen chloride and lowering the level of 5-HT and dopamine in brain soothe the stress. (Chen et al., 2013) Ping-Wei-San, the third most commonly prescribed formula for peptic ulcer, was used traditionally to alleviate distention and fullness in the epigastrium and abdomen, loss of taste and appetite, loose stools or diarrhea, easily-fatigued, increased desire to sleep, nausea and vomiting, belching, acid reflux (Scheid et al., 2009). It has been reported to relieve dyspeptic symptoms of gastrointestinal disorders (Chao et al., 2014a). Jia-Wei-Xiao-Yao-San and Si-Ni-San were widely used to relieve the emotional and psychological symptoms, such as depression or stress (Lin et al., 2015; Tanaka et al., 2013). Huo-Xiang-Zheng-Qi-Tang has been widely used for treatment of various
common gastrointestinal infectious diseases. It was discovered to promote gastroenteric motility, regulate gastrointestinal function and immune response. An earlier study reported that Huo-Xiang-Zheng-Qi-Tang could decrease the level of TNF-α in a murine intestinal infection model (He et al., 2006). Shen-Ling-Bai-Zhu-San has been reported to have an antacid effect (Wu et al., 2010). Ma-Zi-Ren-Wan has been used for functional constipation (Cheng et al., 2011). Bao-He-Ni is also one of the commonly prescribed Chinese herbal formula for post-surgical colon cancer patients (Chao et al., 2014b). Regarding the single herbs, Hai-Piao-Xiao (Os Sepiae) was the most commonly prescribed one. Its chief constituent is 80 to 85 percent of calcium carbonate (Li et al., 2010), which might acts like an antacid to relieve the discomfort resulted from excessive gastric acid. Combination of Hai-Piao-Xiao and Bei-Mu (Bulbus Fritillariae Thunbergii) prevented ethanol-induced gastric lesions in a rat model (Lin, 1998). Yan-Hu-Suo (Rhizoma Corydalis), the second commonly prescribed single herb, is widely used to treat abdominal pain due to qi stagnation (Scheid et al., 2009). It has been reported to inhibit Helicobacter pylori effect (Li et al., 2005), heal ulcer (Tianjiao et al., 2014) and relieve pain (Guo et al., 2014). Bai-Ji (Rhizoma Bletillae) has not only anti-inflammatory but also hemostatic action (Wang et al., 2014b). Chuan-Lian-Zi (Fructus Toosendan) has analgesic effect (Xie et al., 2008).
We included the top 100 herbal formulas to identify the network of core prescriptions for patients with peptic ulcers. The core prescription pattern consisted of “Ban-Xia-Xie-Xin-Tang”, “Hai-Piao-Xiao”, “Yan-Hu-Suo”,” Bei-Mu” and “Chuan-Lian-Zi”. Base on the previous studies on each individual formula and herb, this core pattern can harmonize the stomach and downbear counterflow, control acidity, move qi and relieve pain. It may also regulate the function of the stomach and intestine, control acidity and relieve pain. Some caveats of this study merit comments. First, this study did not include Chinese herbal remedies or decoctions that were purchased directly from TCM herbal pharmacies. Thus, the frequency of utilization might have been underestimated. However, because the NHI system covers TCM prescriptions, which generally cost less than the herbs sold in Taiwan’s markets, the likelihood that subjects purchased a lot of other herbs outside the
NHI database is not high. Second, there was no endoscopic data available to evaluate the healing of ulcers because of the nature of this database. However, the diagnosis and TCM prescriptions were both made by physicians with qualified license, which means the present study has high credibility. These most common formulas and single herbs can be regarded as the consensus candidates for future studies.
5. Conclusions
Our ethnopharmacological study identified the prescription patterns of Chinese herbal products for patients with peptic ulcer diseases. Further basic and clinical studies are warranted to elucidate their mechanism and efficacy.
Acknowledgments
This study was supported by China Medical University under the Aim for Top University Plan of the Ministry of Education, Taiwan. This study was also supported in part by the Taiwan Ministry of Health and Welfare Clinical Trial and Research Center of Excellence (MOHW104-TDU-B-212-113002). This study was based in part on data from the National Health Insurance Research Database, provided by the National Health Insurance Administration, Ministry of Health and Welfare, and managed by National Health Research Institutes. The interpretation and conclusions contained herein do not represent those of National Health Insurance Administration, Ministry of Health and Welfare, or National Health Research Institutes.
Author Contributions
HRY, CYH and WYL conceptualized the study. CCL performed the statistical analysis. CYH, WYL, MFS, BCC, HJL, CHY and HRY contributed to the interpretation of TCM data. CYH, WYL and KCH contributed to the interpretation of pharmacological mechanisms. CYH and WYL contributed equally to draft the manuscript and HRY finalized the manuscript.
Conflict of interest
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Figure Legends
Figure 1. Flow recruitment chart of subjects from the one million samples randomly selected from the National Health Insurance Research Database (NHIRD) from 2001 to 2010 in Taiwan.
Figure 2. The top 100 herbal formulas and single herbs for peptic ulcer patients were analyzed through open-sourced freeware NodeXL. The thicker line width, defined as counts of connections between formulas and herbs, indicated significant prescription patterns in the network.
