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51 DOI : 10.3831/KPI.2009.12.2.051 1) 2) Received : 09. 05. 25 Accepted : 09. 05. 31 Effect of herb drug medicine Treatment for Functional Dyspepsia: Controlled Trial Lee Jae-Jin 1), Son mi-won 2), Hong Kwon-eui 1) Key Words: Herb drug medicine treatment, Functional Dyspepsia, Nepean Dyspepsia Index 1) Dept. of Acupunture & Moxibustation, College of Oriental Medicine, Daejeon University, 2) Dong-A Phamaceutical Co. ABSTRACT Obejective : Functional dyspepsia is a prevalent disease. It impedes subjective quality of life. The purpose of this research is to examine the equivalent effect of herb drug medicine treatment(h-d)and Over the Counter(OTC) for functional dyspepsia. Method : In this controlled study, we compared herb drug medicine(h-d) with Over the Counter(OTC) of functional dyspepsia. 30 volunteers who satisfied the requirements were enrolled in study. Severity of dyspepsia was measured by Nepean Dyspepsia Index(NDI-K) before and after treatments. Result : The results are summarized as follows. 1. In Herb drug medicine and Over the Counter groups, total key symptoms score of after treatment were significantly decreased and improve rate of key symptoms was higher than before treatment, but there were no statistical significance between two groups. 2. In Herb drug medicine and Over the Counter groups, each symptoms score of after treatment were significantly decreased and improve rate of key symptoms was higher than before treatment, but there were no statistical significance between two groups. 3. In Herb drug medicine and Over the Counter groups, quality of life score of after treatment were significantly decreased and improve rate of key symptoms was higher than before treatment, but there were no statistical significance between two groups. Conclusion : Herb drug medicine treatment(h-d) is effective to improve the symptoms and quality of life in patients with functional dyspepsia. I dyspepsia functional dyspepsia Corresponding author : Hong Kwon-eui, Dept. of Acupunture and Moxibustion, College of Oriental Medicine, Daejeon University Tel. 042-229-6816 E-mail : hkeacu@dju.ac.kr

52 12 2 2009 6 25% 2 13.4 25% 30 Herb drug medicine, H-D Over The Counter OTC Nepean Dyspepsia Index NDI-K II 1 2008 7 1 2007 11 30 30 8 22 2 1) 2) KGMP H-D 75 5% 3 (H-D) (OTC) 167 mg 8mg 230mg, 100mg 100 30 mg 12 mg 100mg 150 mg 6 mg 40 mg 167 mg 150 mg 3 mg 0.006 mg 180 mg 16 mg 250 mg 50 mg 20 75

53 H-D OTC 1 3 1 1 2 2 3) 4) 1 20 70 2 Rome Criteria Table 1 3 2 2 6 0 mild 1 moderate 2 severe 3 5) 1 2 3 2 4 5 6 6) H-D OTC NDI-K 2 1 3 NDI-K NDI-K CRF Case Report Form CRF dropout 7) NDI-K 1 NDI-K 15 2 5 6 5 25 5 1 5 8)

54 12 2 2009 6 1 NDI-K 8 2 NDI-K 15 NDI-K NDI-K NDI-K Fig 1 9) t paired t-test t independent t-test Fisher s exact test Kappa Windows SAS 9.1 p p-value 0.05 Table 3 3 Table 4 4 NDI-K NDI-K 15 8 Table 5 1) NDI-K NDI-K 8 p=0.002 p=<0.0001) Table 6 III 1 30 H-D OTC 15 Table 2 2 5 NDI-K 15 1) NDI-K 15 NDI-K Table 7 2) NDI-K 15 H-D NDI-K

55 12 Table 8 7 3) OTC NDI-K 15 OTC NDI-K 10 Table 9 4) NDI-K 15 NDI-K Table 10 6 NDI-K 1) NDI-K NDI-K Table 11 2) H-D NDI-K H-D NDI-K Table 12 3) OTC NDI-K OTC NDI-K Table 13 4) NDI-K 15 NDI-K Table 14 IV 25% 38-41% 32% 13.4% 15.4% 15.5% 25% dyspepsia 3 81%

56 12 2 2009 6 OTC 30 H-D OTC Nepean Dyspepsia Index NDI- K H-D OTC H-D 1 20 OTC 1 75 30 H-D OTC 15 Table 2 H-D 4:11 Table 3

57 H-D OTC 73.33, 86.67 % Table 4 H-D OTC 40,00, 40.00 % Table 4 Table 4 NDI-K Talley NDI-K 15 8 Table 5 NDI-K 8 p=0.002, p=<0.0001 Table 6 H-D OTC NDI-K 15 NDI-K Table 7 H-D NDI-K H-D 12 Table 8 OTC 10 Table 9 H-D NDI-K NDI-K Table 11 NDI- K H-D Table 12 OTC Table 13 Table 14

58 12 2 2009 6 H-D OTC H-D V 30 H-D OTC NDI-K 1 NDI-K 2 NDI-K 3 NDI-K VI 1. Choi MG. Definition and Epidemilogy of Functional Dyspepsia. The Korean Society of Gastrointestinal Motility. 2000;6:235-40. 2. Lee JH, Kim HY, Rho SH, Yoon DH, Kim KH, Choi JH. Which Patients do examinate Endoscopy Test on Functional Dyspepsia in Korea. The Korean Society of Gastrointestinal Motility. 2001;22:1-7. 3. Park YT. Approch Definition and Diagnosis of Dyspepsia, Seoul, Jin publishing. 2006:13-29. 4. Talley NJ, Stanghellini V, Heading RC, Koch KL, Malagelada JR, Tytgat GN. Functional gastroduodenal disorders. Gut. 1999;45(Suppl ):37-42. 5. Huh C, Yang CH, Jang JG, Lee DH, Lee GL, Seol SY, Lee YJ, Han YS, Rim KS, Rhee PL, Shin WC, Lee KJ, Chung MK, Na YH. Functional Dyspepsia and Subgroups in Korea and Short Term Outcome of Therapeutic Trial of Cisapride ; Multicenter Study. The Korean Society of Gastrointestinal Motility. 1998;4(1):1-12. 6. Lee SY, Choi CH, Lee HY, Do MY, Lee SH, Han SP, Huh C, Kin HJ, Kim JY, Kim JG, Jang SK, Park SM. Original Articles : The Frequency of Functional Dyspepsia Subtypes and its Related Factors for Health Check up Subjects. The Korean Society of Gastrointestinal Motility. 2007;13:31-7. 7. Seoul: Dong-Woo Publishing co. 2000:51-62, 65-74, 83-8, 154-9. 8. Effects of Mosapride on Upper Gastrointestinal Symptoms and Gastric Emptying in Patients with Functional Dyspepsia. The Korean Society of Gastrointestinal Motility. 2004;10(1):27-34. 9. A Randomized Study to Compare Domperidone Maleate with Itopride Hydrochloride in Dysmotility-type Functional Dyspepsia. The Korean Society of Gastrointestinal Motility. 2003;41:284-9. 10. 2002;16(2):199-213. 11. 2003;24(2):329-36. 12. 2005;26(3):641-51. 13.

59 2007;28(2):242-9. 14. 2008:1-29. 15. 2007;28(2):209-16. 16. Jones RH, Lydeard SE, Hobbs FD. Dyspepsia in England and Scotland. Gut. 1990;31:401-5. 17. Agreus L, Svardsudd K, Nyren O, Tibblin G. Irritable bowel syndrome and dyspepsia in the general population: overlap and lack of stability over time. Gastroenterology. 1995;109:671-80. 18. 1999;20(2):176-85. 19. Kim HS, Lee GJ, Kim JH, Ham KB, Cho SW. Functional Gastrointestinal Disorders in Patients Referred to Specialist Gastroenterologists in a Tertiary Hospital. The Korean Society of Gastrointestinal Motility. 2004;10(2):111-7. 20. Lee GJ. Pathophysiology and Treatment of Functional Dyspepsia. The Korean Society of Gastrointestinal Motility 2003;9:85-91. 21. Lee GJ. Guidline of Treatment on Functional Dyspepsia. The Korean Society of Gastrointestinal Motility. 2005;11(3):25-9. 22. Ko KB. Aspect of Spycosociology for functional dyspepsia. The Korean Society of Gastrointestinal Motility. 2000;6:258-66. 23. 1998;289-90, 291-2, 334-5, 336-7, 342-3, 344-5, 348-9, 413-4, 612-3. 24. 2008;1202-1203 25. Bond EF, Heitkemper MM, Bailey SL. Estrogen suppresses gastric motility response to thyrotropin-releasing to hormone and stress in awake rats. Res Nurs Health. 1998;21(3):221-8. 26. Heitkemper MM, Bond EF. Gastric motility in rats with varying ovarian hormone status. Res Nurs Health. 1995;17(1):9-19. 27. 2005:135-44 28. Park YC, Jo JH, Hong KE, Jung YC, Kang WC, Choi SM. Effect of Acupuncture Treatment for Functional Dyspepsia: A Randomized Controlled Trial. The Journal of Korean Acupuncture and Moxibustion Society. 2007;24(1):1-12. 29. Talley NJ, Haque M, Wyeth JW, Stace NH, Tytgat GN, Stanghellini V, Holtmann G, Verlinden M, Jones M. Development of a new dyspepsia impact scale: the Nepean Dyspepsia Index. Aliment Pharmacol Ther. 1999;13(2):225-35. 30. Talley NJ, Verlinden M, Jones M. Validity of a new quality of life scale for functional dyspepsia: a United States multicenter trial of the Nepean Dyspepsia Index. Am J Gastroenterol. 1999;94(9):2390-7 31. Talley NJ, Verlinden M, Jones M. Quality of life in functional dyspepsia: responsiveness of the Nepean Dyspepsia Index and development of a new 10-item short form. Aliment Pharmacol Ther. 2001;15(2):207-16 32. Katz S. The science of quality of life. J Chronic Dis. 1987;40:459-63. 33. Choi MG. Quality of Life in Functional Dyspepsia. The Korean of Gastroenterology. 2002;spr:55-65. 34. Jo YK, Choi MG, Kim SH, Lee YS, Kim SY, Jeong YS, Lee SL, Choi SC, Seol SY. The Effect of Mosapride on Quality of Life in Functional Dyspepsia. The Korean of Gastroenterology. 2004;43(3):160-7.

60 12 2 2009 6 Research Doctor statistician Research Doctor Pharmacist Research Doctor H-D& OTC screening assignment NDI-K during 2wk NDI-K Fig. 1. Design of study. NDI-K: Nepean dyspepsia index H-D: Herb drug medicine treatment OTC: Over The Counter Table 1. Definition of Functional Dyspepsia in Rome Criteria 2) At least 12 weeks, which need not be consecutive, in the preceding 12 months of: 1. Persistent or recurrent symptoms (pain or discomfort centered in the upper abdomen); 2. No evidence of organic disease that is likely to explain the symptoms; and 3. No evidence that dyspepsia is exclusively relieved by defecation or associated with the onset of a change in stool frequency or stool form (i.e., not irritable bowel). Table 2. Clinical Characteristics of Two Patients Groups Treated with H-D and OTC H-D OTC Fisher s exact test p-values T-test Total number 15 15 Gender(n(%)) Male 4(26.7%) 4(26.7%) Female 11(73.3%) 11(73.3%) 1.0 Mean Age(y) 43.4 11.4 a) 34.7 10.7 0.040 Height( ) 162.8 8.4 163.3 6.90 0.869 Weight( ) 61.26 11.6 59.86 9.96 0.726 Severity of dyspepsia symptom 9.66 1.87 8.60 1.12 0.069 a) : Mean standard deviation Table 3. Surmise about Treatment in Two Patients Groups Treated with H-D and OTC H-D OTC Kappa(95% CI) Surmise about treatment(%) H-D OTC 11(73.3) 4(33.3) 5(26.7) 10(66.7) 0.40 (0.07-0.73)

61 Table 4. Subtype and Byeonjeung Type of Functional Dyspepsia in Treated with H-D and OTC H-D OTC Fisher s exact test Ulcer-like Dyspepsia 1(6.67) 1(6.67) Subtype Dysmotility-like Dyspepsia 11(73.33) 13(86.67) 0.791 Unspecified Dyspepsia 3(20.00) 1(6.67) Disharmony between liver and stomach syndrome 6(40.00) 6(40.00) Stagnated meal syndrome 2(13.33) 2(13.33) Byeonjeung Type Spleen-stomach dampness-heat syndrome 0(0.00) 1(6.67) 1.000 Simultaneous occurrence of cold and heat syndrome 3(20.00) 2(13.33) Hypofunction of spleen and stomach syndrome 4(26.67) 4(26.67) Table 5. Mean Changes of Dyspepsia Key Symptoms between before and after Treatment NDI-K score H-D OTC p-value b) Before treatment 51.73 15.04 a) 43.87 17.00 0.190 After treatment 27.33 14.94 18.93 10.69 0.934 a): Mean standard deviation b): independent t-test Table 6. Mean changes of dyspepsia key symptoms between before and after treatment with H-D and OTC NDI-K score Mean change Paird t-test H-D -24.40 18.73 a) 0.0002*** OTC -24.93 16.12 0.0001*** p-value b) 0.934 a): Mean standard deviation b): independent t-test (***: p 0.001)

62 12 2 2009 6 Table 7. Score of NDI-K Symptoms in the Two Group Before Treatment Symptom H-D OTC p-value b) Pain in upper abdomen 6.00 2.27 a) 4.33 3.85 0.162 Discomfort in upper abdomen 7.80 1.82 7.20 2.34 0.439 Burning in upper abdomen 5.93 2.63 3.67 3.04 0.038* Inability to finish a regular meal 7.33 2.55 6.47 3.02 0.403 Fullness after eating 7.67 2.60 8.47 2.85 0.429 Pressure in upper abdomen 6.00 3.72 4.60 4.04 0.333 Bloating in upper abdomen 6.13 2.88 6.33 2.94 0.852 Nausea 4.87 3.98 2.80 2.86 0.114 Heartburn 4.20 3.28 0.93 1.67 0.003* Cramps in upper abdomen 3.53 3.38 1.40 2.29 0.053 Chest pain 4.06 3.24 1.73 2.52 0.036* Bitter tasting fluid that comes to your mouth 4.47 3.58 3.87 3.29 0.637 Burping 6.53 3.44 6.40 2.85 0.909 Vomiting 2.80 3.47 1.20 2.57 0.162 Bad breath 3.27 3.37 1.33 2.02 0.069 Total symptom score 80.60 29.95 60.73 22.62 0.050* a): Mean standard deviation. b): independent t-test (*: p 0.05)

63 Table 8. Mean Changes of NDI-K Symptoms in the Group Treated with H-D Symptom After score Mean change Parid t-test Pain in upper abdomen 2.80 2.31 a) -3.20 3.17 0.002** Discomfort in upper abdomen 4.40 2.50-3.40 3.44 0.002** Burning in upper abdomen 3.47 3.00-2.47 3.16 0.009** Inability to finish a regular meal 3.00 3.12-4.33 4.20 0.001*** Fullness after eating 4.27 3.39-3.40 3.39 0.001*** Pressure in upper abdomen 3.20 2.65-2.80 3.69 0.011* Bloating in upper abdomen 3.47 3.36-2.67 3.13 0.005** Nausea 2.73 2.94-2.13 4.14 0.066 Heartburn 2.60 3.11-1.60 3.36 0.086* Cramps in upper abdomen 1.20 2.04-2.33 4.34 0.056 Chest pain 0.80 1.26-3.27 3.13 0.001*** Bitter tasting fluid that comes to your mouth 1.27 1.98-3.20 2.83 0.001*** Burping 4.60 4.10-1.93 4.89 0.148 Vomiting 0.73 1.58-2.07 3.15 0.023* Bad breath 0.66 1.18-2.60 3.11 0.006** Total symptom score 39.20 20.16-41.40 29.64 0.0001*** a): Mean standard deviation. (*: p 0.05, **: p 0.01, ***: p 0.001)

64 12 2 2009 6 Table 9. Mean Changes of NDI-K Symptoms in the Group Treated with OTC Symptom After score Mean change Parid t-test Pain in upper abdomen 1.60 1.88-2.73 3.49 a) 0.009** Discomfort in upper abdomen 2.60 2.13-4.60 2.92 0.0001*** Burning in upper abdomen 1.80 2.14-1.87 2.29 0.007** Inability to finish a regular meal 2.73 2.63-3.73 2.60 0.0001*** Fullness after eating 4.07 2.66-4.40 3.25 0.000*** Pressure in upper abdomen 1.73 2.07-2.87 4.27 0.021* Bloating in upper abdomen 2.47 2.45-3.87 3.81 0.002** Nausea 1.93 3.41-0.87 4.34 0.452 Heartburn 0.33 1.29-0.60 1.24 0.082 Cramps in upper abdomen 0.40 1.06-1.00 2.51 0.145 Chest pain 0 0-1.73 2.52 0.019* Bitter tasting fluid that comes to your mouth 2.07 2.02-1.80 2.86 0.029* Burping 2.53 2.03-3.87 3.68 0.001** Vomiting 0.53 1.46-0.67 3.18 0.430 Bad breath 0.40 1.12-0.93 1.83 0.068 Total symptom score 25.20 14.15-35.53 20.87 0.0001*** a): Mean standard deviation. (*: p 0.05, **: p 0.01, ***: p 0.001)

65 Table 10. Mean Changes of NDI-K Symptoms in Two Patients Groups Treated with H-D and OTC Symptom H-D OTC p-value b) Pain in upper abdomen -3.20 3.17 a -2.73 3.49 a) 0.704 Discomfort in upper abdomen -3.40 3.44-4.60 2.92 0.312 Burning in upper abdomen -2.47 3.16-1.87 2.29 0.557 Inability to finish a regular meal -4.33 4.20-3.73 2.60 0.642 Fullness after eating -3.40 3.39-4.40 3.25 0.405 Pressure in upper abdomen -2.80 3.69-2.87 4.27 0.964 Bloating in upper abdomen -2.67 3.13-3.87 3.81 0.354 Nausea -2.13 4.14-0.87 4.34 0.420 Heartburn -1.60 3.36-0.60 1.24 0.288 Cramps in upper abdomen -2.33 4.34-1.00 2.51 0.311 Chest pain -3.27 3.13-1.73 2.52 0.150 Bitter tasting fluid that comes to your mouth -3.20 2.83-1.80 2.86 0.189 Burping -1.93 4.89-3.87 3.68 0.232 Vomiting -2.07 3.15-0.67 3.18 0.236 Bad breath -2.60 3.11-0.93 1.83 0.085 Total symptom score -41.40 29.64-35.53 20.87 0.536 a): Mean standard deviation. b): independent t-test Table 11. Quality of Life Score of NDI-K Symptoms in the Two Group Before Treatment Quality of Life H-D OTC p-value b) Interference 73.97 9.28 a) 69.23 16.69 0.346 Knowledge/Control 57.14 12.37 61.90 24.21 0.505 Eat/drink 66.11 17.67 24.21 21.33 0.490 Sleep disturb 80.00 9.21 82.50 16.90 0.620 Total symptom score 69.31 7.29 71.19 16.99 0.698 a): Mean standard deviation. b): independent t-test

66 12 2 2009 6 Table 12. Mean Changes of NDI-K Quality of Life Score in the Group Treated with H-D Quality of Life After score Mean change Paird t-test Interference 89.36 10.17 a) 15.38 10.70 0.0001*** Knowledge/Contro l78.10 14.47 20.95 10.17 0.0001*** Eat/drink 76.67 17.67 10.56 20.76 0.0691 Sleep disturb 88.33 11.05 8.33 12.20 0.0192* Total symptom score 83.11 9.44 13.80 9.36 0.0001*** a): Mean standard deviation. *:p 0.05, ***: p 0.0001. Table 13. Mean Changes of NDI-K Quality of Life Score in the Group Treated with H-D Quality of Life After score OTC Paird t-test Interference 89.87 12.64 a) 20.64 20.86 0.002** Knowledge/Control 61.90 16.49 24.52 26.24 0.003** Eat/drink 86.42 18.69 26.24 20.04 0.061 Sleep disturb 95.83 7.72 13.33 16.00 0.006** Total symptom score 88.45 11.06 17.26 18.26 0.003** a): Mean standard deviation. *: p 0.01. Table 14. Mean Changes of NDI-K Symptoms in Two Patients Groups Treated with H-D and OTC Quality of Life H-D OTC p-value b) Interference 15.38 10.70 a) 20.64 20.86 a) 0.3951 Knowledge/Control 20.95 10.17 24.52 26.24 0.6290 Eat/drink 10.56 20.76 26.24 20.04 1.0000 Sleep disturb 8.33 12.20 13.33 16.00 0.3440 Total symptom score 13.80 9.36 17.26 18.26 0.5212 a): Mean standard deviation. b): independent t-test