Nghiên cứu độc tính, tác dụng an thần trên thực nghiệm và điều trị mất ngủ không thực tổn trên lâm sàng của cao lỏng dưỡng tâm an thần tt tiếng anh

1 INTRODUCTION Sleep is an important indicator of health and well-being in life Sleep deficiency can lead to physical and mental health problems, injuries, loss of productivity, and even a greater risk of death Numerous epidemiological studies have discovered that about 20% - 30% of the adult population, this rate increases in the elderly Along with the development of modern medicine, traditional medicine has affirmed itself and at the same time has made significant contributions to the health care for the community Insomnia is described in the scope of "shimian" of traditional medicine, the main manifestation is hard to fall asleep, hard to stay asleep Traditional medicine (traditional medicine) has effective drugs for insomnia The remedy Duong tam an than of Thanh Hoa Traditional Medicine Hospital is originated from TianWanBuXinDan remedy, which has been modified based on practical treatment experience at the hospital The remedy needs to be scientifically evaluated and comprehensive according to the regulations of the Ministry of Health to be widely applied in clinical Therefore, we carried out the thesis: "Research on toxicity, sedative effects on experimental and clinical treatment of non-organic insomnia “Duong tam an than” liquid" with the following objectives: Determine the acute toxicity and sub-chronic toxicity of “Duong tam an than” liquid on experimental Evaluate the sedative effects of “Duong tam an than” liquid on experimental animal models Evaluate the effect of “Duong tam an than” liquid on non-organic insomnia patients NEW CONTRIBUTIONS OF THE THESIS Scientific significance The study has obtained specific, reliable results on sedative effects on experimental and clinical studies, as a basis for further studies on a larger model for more herbal developes which treatment of nonorganic insomnia Practical significance Non-organic insomnia has been receiving a great deal of public attention, local and international researchers even, because of directly affects to health and quality of daily life, memory, concentration, alertness and mood, which also results in reduce learning ability, less working efficiency, fatigue, loss of appetite, etc This means that non-organic insomnia can even lead to serious accidents which boosts increase the incidence of disease or dead even, etc Therefore, the studied “Duong tam an than” liquid has provided scientific evidence on the effect of regulating sleep as well as undesirable effects in case it happens Thereby contributing to providing a herbal medicine product to help treat a common clinical disease NEW CONTRIBUTIONS *Acute toxicity, subchronic toxicity of “Duong tam an than” liquid on experimental animals - Acute toxicity of “Duong tam an than” liquid in albino mice orally: at the dose of 17g condensed liquid/kg/day (≈ 11 clinical dose) (=38,42g of dried herb/ kg/day) In result, mice did not die within 24 hours but became inactive, overslept and suffered from diarrhea did not die within 24 hours, were inactive, slept, and diarrhea; LD50 has not been determined - Subchronic toxicity of “Duong tam an than” liquid in albino rats via oral use: at dose of 9,24 g condensed liquid/kg/day ( = 20.88 g of dried herb/ kg/day, conversion factor is six) and 27, 72 g condensed liquid/kg/day ( = 62.64 g of dried herb/kg/day ≈ clinical dose) using continuously for weeks showed no effect on general condition, weight, and indicators of hematopoietic function evaluation, liver function, level of liver cell destruction and filtering function of the kidney, and anatomic pathology of the liver and the kidney 3 * Sedative effect of DTAT liquid on experimental hour and hours after admission, DTAT liquid in both clinical dose (41.76 g dried herb/kg/day) and fold clinical dose (125.28 g dried herb / kg / day) shows the sedative effect: - Increase the number of entries, the time spent on the open arm; reduce the rate of the avoidance on the open arm Reduce the time spent on the close arm Reduce the number of times the mouse moves horizontally and vertically - Reduce the grip strength time and reduce the grip of white mouse on Rotarod horizontal rod and on grip strength apparatus The effect between two doses is similar * Sedative effect of sedative liquid sedative on clinical: After 30 days of treatment, “Duong tam an than” liquid has shown good effects on treating insomnia patients: Reduce time of falling asleep: The rate of patients falling asleep in 0,05 p 0,05 p (compared to lot 3) p > 0,05 p > 0,05 p > 0,05 p > 0,05 Comment: Rats in lots used diazepam and YXAS liquid both showed relieved anxiolytic compared to sham, with p 0.05) 3.1.3.2 Research results of Rotarod rotary axis model Table 3.3: Effect of Duong tam an than liquid (YXAS) on the gripping time of the rats on rotarod rotating axis 11 Lô Lot (Sham) Lot (Diazepam dose of 2,4g/kg) p (compared to lot 1) Lot (Duong tam an than liquid dose equivalent clinical dose) p (compared to lot 1) p (compared to lot 2) Lô (Duong tam an than liquid dose fold clinical dose) p (compared to lot 1) p (compared to lot 2) p (compared to lot 3) Time that rats sticked with rotarod rotating axis Start time of the hour after hours after study taking medicine taking medicine 247,8 ± 70,3 251,3 ± 48,2 249,6 ± 70,8 238,0 ± 67,3 170,9 ± 50,0 219,6 ± 82,4 p > 0,05 p < 0,05 p > 0,05 229,0 ± 95,2 178,5 ± 63,8 239,1 ± 62,6 p > 0,05 p > 0,05 p < 0,05 p > 0,05 p > 0,05 p > 0,05 232,9 ± 123,6 146,2 ± 94,0 244,3 ± 54,0 p > 0,05 p > 0,05 p > 0,05 p < 0,05 p > 0,05 p > 0,05 p > 0,05 p > 0,05 p > 0,05 Comment: at hour after rats taking diazepam and rats of lots used YXAS liquid showed sedative effect by reduction the gripping time of the rats on rotarod rotating axis compared to sham (p0.05) 3.1.3.3 Research results of the activity log model Table 3.4: Effects of Duong tam an than liquid (YXAS) to horizontal movement of the rats The number of horizontal movement Lot hour after hour after Before research taking medicine taking medicine ( Sham) 241,80 ± 40,93 247,40 ± 37,30 247,20 ± 33,99 (Diazepam dose of 2,4g/kg) 245,20 ± 59,62 201,00 ± 47,40 196,53 ± 64,15 p (compared to lot 1) p > 0,05 p < 0,05 p < 0,05 (Duong tam an than liquid 243,40 ± 44,72 209,10 ± 40,75 208,43 ± 40,18 dose equivalent clinical dose) p (compared to lot 1) p > 0,05 p < 0,05 p < 0,05 p (compared to lot 2) p > 0,05 p > 0,05 p > 0,05 (Duong tam an than liquid 246,40 ± 47,40 208,30 ± 41,16 202,21 ± 46,27 dose equivalent clinical dose) p (compared to lot 1) p > 0,05 p < 0,05 p < 0,05 p (compared to lot 2) p > 0,05 p > 0,05 p > 0,05 p (compared to lot 3) p > 0,05 p > 0,05 p > 0,05 Comment: Rats of lots used diazepam and YXAS liquid showed decrease activity compared to sham at the times after taking medicine: reduction of the number of horizontal movement (p 0.05) 12 Table 3.5: Effects of Duong tam an than liquid (YXAS) on vertical movement of rats The number of vertical movement Lot hour after hour after Before research taking medicine taking medicine ( Sham) 19,30 ± 6,07 20,60 ± 5,46 20,20 ± 3,65 (Diazepam dose of 18,87 ± 5,14 12,67 ± 3,81 13,53 ± 3,58 2,4g/kg) p (compared to lot 1) p > 0,05 p < 0,05 p < 0,05 ( Duong tam an than liquid 19,14 ± 4,69 16,00 ± 3,04 15,64 ± 3,61 dose equivalent clinical dose) p (compared to lot 1) p > 0,05 p < 0,05 p < 0,05 p (compared to lot 2) p > 0,05 p > 0,05 p > 0,05 (Duong tam an than liquid 19,79 ± 6,99 14,93 ± 4,45 14,43 ± 4,20 dose fold clinical dose) p (compared to lot 1) p > 0,05 p < 0,05 p < 0,05 p (compared to lot 2) p > 0,05 p > 0,05 p > 0,05 p (compared to lot 3) p > 0,05 p > 0,05 p > 0,05 Comment: Rats of lots used diazepam and YXAS liquid showed decrease activity compared to sham at the times after taking medicine: reduction of the number of vertical movement (p 0.05) 3.1.3.4 Research results of the grip measurement model: Table 3.6: Effects of Duong tam an than liquid (YXAS) on the grip force of the rats The grip force of the rats (g) Lot hour after taking hours after medicine taking medicine Lot (Sham) 353,20 ± 60,85 352,13 ± 63,13 Lot (Diazepam dose of 2,4g/kg) 261,73 ± 62,64 286,20 ± 72,83 p (compared to lot 1) p < 0,001 p < 0,05 Lot (Duong tam an than liquid dose 226,93 ± 71,52 247,33 ± 63,06 equivalent clinical dose) p (compared to lot 1) p < 0,001 p < 0,001 p (compared to lot 2) p > 0,05 p > 0,05 Lot (Duong tam an than liquid dose fold 248,20 ± 46,89 250,40 ± 41,06 clinical dose) p (compared to lot 1) p < 0,001 p < 0,001 p (compared to lot 2) p > 0,05 p > 0,05 p (compared to lot 3) p > 0,05 p > 0,05 Comment: at the times after taking diazepam and YXAS liquid, rats reduced the grip force compared to sham (p0.05) 13 3.2 CLINICAL RESEARCH RESULTS OF DUONG TAM AN THAN LIQUID 3.2.1 Characteristics of the research object p > 0,05 Chart 3.1: Distribution of patients by age Comment: The age group had the highest rate of insomnia was 45 - 60 years old and 30 - 44 years old and there is no difference in the rate of disease by age between groups (p> 0.05) Table 3.7: Distribution of patients by gender The group Studied group (n=110) Controlled group (n=55) Gender Amount Ratio % Amount Ratio % Male 29 26,36 10 18,18 Female 81 73,64 45 81,82 Total 110 100 55 100 p p(NC-ĐC) > 0,05 Comment: The rate of female insomnia was higher than that of men (p 0.05 3.2.2 The effects of Duong tam an than liquid Table 3.8: The change of time going to sleep over time Time < 15 15-