As the elderly population in China is increasing year by year, the problem of insomnia in the elderly is gradually emerging, and 80% of the elderly are troubled by sleep quality problems [1]. Endogenous regulation plays a strong role in sleep-wake in elderly people, and the change of circadian rhythm gradually increases with their age, and the older they are, the smaller the amplitude of circadian regulation and the earlier the generation of circadian rhythm; changes in 5-HT and DA levels are closely related to the generation of insomnia and its endogenous regulatory changes in elderly people [2-3]. Therefore, in this study, we observed the clinical efficacy of Zhenzao capsule on insomnia of Yin deficiency and fire type in the elderly, and observed the changes of 5-HT and DA levels in order to elaborate the mechanism of action of Zhenzao capsule in improving sleep quality from the molecular biology perspective. Xu
1.General information
Patients with yin deficiency and fire type insomnia in geriatric wards, of either sex, aged 60-80 years, without obvious organic diseases of brain, lung, liver, kidney and endocrine; were entered into treatment and control groups of 30 cases each through a randomized, blinded, parallel-controlled clinical study. There were 17 males and 13 females in the treatment group and 14 males and 16 females in the control group; the highest age in the treatment group was 80 years old and the lowest was 63 years old, while the highest age in the control group was 79 years old and the lowest was 64 years old. the data of the patients in the 2 groups before treatment in terms of number of cases, gender, age and TCM evidence points were statistically processed, and the differences were not statistically significant P>0.05 and were comparable.
2 Diagnostic criteria
2.1 Diagnostic criteria for TCM identification: refer to the Clinical Experimental Guidelines for the Treatment of Insomnia by New Chinese Medicines [4] to develop.
2.1.1 Typical symptoms of insomnia: difficulty in falling asleep, frequent waking, unstable sleep or not easy to fall asleep again after waking, early waking, drowsiness during the day, sleep for less than 5 hours; with a history of recurrent episodes.
2.1.2 TCM criteria: The main symptoms of insomnia with yin deficiency and fire are disturbed sleeplessness or dreamy wakefulness. Concurrent symptoms: dizziness, dry mouth, tinnitus, forgetfulness, palpitations, lumbar and knee weakness, spermatorrhea, zygomatic redness and hot flashes, red tongue, thin or fine pulse.
2.2 Western medical diagnostic criteria: formulated with reference to the Chinese Classification and Diagnostic Criteria of Mental Disorders (CCMD-3) [5].
Insomnia was the main or only symptom, and symptoms included difficulty in falling asleep, shallow sleep, early waking or inability to fall asleep after waking, fatigue and discomfort after waking or daytime sleepiness. The onset was greater than or equal to 3 times per week and lasted for more than 1 month.
3. Inclusion, exclusion and discontinuation criteria
3.1 Inclusion criteria
3.1.1 Meet the diagnostic criteria of Western medicine.
3.1.2 Meet the TCM diagnostic criteria and TCM symptom criteria.
3.1.3 Subjects were aged 60-80 years.
3.1.4 No restriction on the subject’s gender.
3.1.5 Patients with severe mental disorders and somatic diseases were excluded.
3.1.6 Patients who are informed and agree to this clinical study.
3.2 Exclusion criteria
3.2.1 Those who do not meet the inclusion criteria.
3.2.2 Those with secondary insomnia.
3.2.3 Those with combined severe psychiatric disease or serious disorders of cardiovascular, hematopoietic system, liver and kidney function.
3.2.4 Those who are younger than 60 years old or older than 80 years old.
3.2.5 Persons with drug allergy or allergic constitution.
3.2.6 Those who are unwilling to cooperate or have poor compliance.
3.3 Discontinuation criteria
3.3.1 Those who have serious adverse events in the clinical study.
3.3.2 Allergy to the drug occurs during the clinical study.
3.3.3 Those who do not want to continue the clinical study.
3.3.4 For other reasons, the continuation of the clinical study must be terminated.
3.3.5 Self-administration of drugs other than this study drug for the treatment of insomnia.
3.3.6 Those who self-administer psychotropic drugs.
4.Treatment plan
Treatment group: 0.38g per capsule, 5 capsules/time per day, taken orally half an hour before bedtime Control group: 0.4g per capsule, 5 capsules/time per day, taken orally half an hour before bedtime
All groups took the medicine continuously for 4 weeks as a course of treatment, with a follow-up examination every 7 days. The observation time is 1 course of treatment.
5.Observation items
5.1 General recording items
Randomization number, group, subject’s initials, hospitalization number, date of beginning, course and end of the trial, blood pressure, heart rate, etc.
5.2 Observation indexes
5.2.1 Safety indicators
The electrocardiogram, blood routine, urine routine, stool routine, liver function and kidney function of 60 patients were tested before and after treatment.
5.2.2 5-HT and DA detection
Blood specimens were taken from patients before and early in the morning after 4 weeks of drug administration, and the blood specimens were centrifuged sufficiently and plasma was collected, and the 5-HT and DA contents were measured by using 5-HT and DA test kits in strict accordance with the prompted steps, respectively.
6.Efficacy evaluation criteria
6.1 Clinical efficacy evaluation The clinical efficacy evaluation criteria of insomnia were developed with reference to the Clinical Research Guidelines for the Treatment of Insomnia with New Chinese Medicines [3].
①Cure: normal sleep duration or more than 6 hours of sleep duration, stable sleep, mental and energetic after waking up.
②Significantly effective: the sleep quality is significantly better, and the sleep length is at least 3 hours longer than before.
③Effective: Sleep quality is mildly improved and sleep duration is increased by less than 3 hours.
④Invalid: no improvement or even worsening of sleep quality and length.
6.2 Efficacy of TCM symptoms According to the “Clinical Research Guidelines for TCM symptoms – Criteria for determining the efficacy of symptoms” and with reference to the “Guidelines for Clinical Research on New Chinese Medicines” [3], the point method was used to evaluate the efficacy of TCM symptoms (see Table 1 for details of the TCM Yin deficiency and fire type point scale).
Treatment index (N) = (pre-treatment score – post-treatment score) / pre-treatment score × 100%.
①Cure: Treatment index between 76% and 100%.
②Effective: Treatment index between 51% and 75%.
③Effective: treatment index between 25% and 50%.
④Ineffective: treatment index less than 25%.
7. Statistical methods
SPSS19.0 statistical software was used, and the data were expressed as mean ± standard deviation ( ± s) for the measurement data; and the count data were expressed as percentages. For the comparison of two groups, the paired t-test was used for the case that the measurement data met normal distribution, and the t-test was used for the case that the variance did not meet normal distribution; the nonparametric test was used for the case that the distribution did not meet normal distribution; the χ2 test was used for the count data; the Wilcoxon rank sum test was used for the rank data; and the two-sided test was used for the hypothesis test. p less than or equal to 0.05 was statistically different, and p less than or equal to 0.01 is statistically significantly different.
8. Study results
8.1 Analysis of general conditions of patients in both groups
As can be seen from Table 1, the number of cases, gender, age, and Chinese medicine symptom score before treatment in the two groups of this study, the gap between the groups was not statistically significant, P>0.05.