ABSTRACT
Objective:To observe the efficacy and safety of dexzopiclone plus auricular acupressure in intervening primary insomnia.Methods:A total of 72 participants who met the inclusion criteria were enrolled in a randomized controlled trial,with 36 cases allocated to a treatment group and 36 cases allocated to a control group.Both groups were given dexzopiclone as the routine treatment.Patients in the treatment group were given auricular acupressure with Wang Bu Liu Xing (Semen Vaccariae) seeds at the auricular acupoints related to sleep and emotion based on meridian theory,whereas for patients in the control group,the medical plasters with Wang Bu Liu Xing (Semen Vaccariae) seeds were only gently stuck to acupoints unrelated to sleep without stimulation.Patients in both groups were required to visit the hospital once a week for replacing the seeds and plasters.The course of intervention lasted for 8 weeks and the patients were followed up for another 4 weeks.Pittsburgh sleep quality index (PSQI) and Karolinska sleep diary (KSD) were used to evaluate the outcomes.Meanwhile,adverse effects were monitored and recorded.Results:In the enrolled 72 cases,4 patients (one in the treatment group and three in the control group) reported thirst and a bitter taste,and one case in the control group reported nausea and vomiting.At last,3 cases in the control group dropped out for adverse reactions,and 69 cases completed the clinical trial.After 8 weeks of treatment,the global scores of PSQI in both treatment and control groups decreased significantly compared with the baseline (both P＜0.001).Furthermore,the global score of PSQI in the treatment group was lower than that in the control group (P＜0.01).The global scores of PSQI in both groups at the follow-up were significantly different from the baseline (both P＜0.001),but insignificantly different compared with the post-treatment results (both P＞0.05).According to KSD,both treatment protocols could prolong the total sleep time,shorten sleep-onset latency,improve sleep efficacy and sleep quality significantly,and the changes in the treatment group were more significant.The total effective rate was 88.9％ in the treatment group,higher than 81.8％ in the control group,though the difference was statistically insignificant (P＞0.05).Conclusion:Dexzopiclone plus auricular acupressure is effective and safe for patients with primary insomnia both in short and long terms,and it is more effective than monotherapy of dexzopiclone.
ABSTRACT
OBJECTIVE:To prepare Dexzopiclone orally disintegrating tablets (DODT),and to optimize its formulation.METHODS:Direct powder compression method was used to prepare DODT.Using repose angle of material,disintegration time and taste evaluation as indexes,single factor test was used to screen the types or amount of bulking agent,disintegrating agent,glidant and flavoring agent;using disintegration time as index,orthogonal experiment was applied to optimize the proportion of bulking agent,the amount of disintegrating agent,glidant and flavoring agent.Then the hardness and main component contents of DODT prepared by optimal formulation were determined.RESULTS:The optimal formulation was as follows as the ratio of mannitol-MCC 1 ∶ 4,the amount of disintegrating agent PVPP was 15％,the amount of glidant magnesium stearate was 1.0％,the amount of flavoring agent stevia was 3.0％.Three batches of prepared DODT were smooth in surface and good in taste;their disintegration time were(26.7 ± 1.2),(26.7 ± 0.6),(27.6 ± 0.9)s,hardness were (3.59 ± 0.19),(3.49 ± 0.18),(3.27 ± 0.16) kg,and contents were (99.47 ± 0.15) ％,(99.53 ± 0.05)％,(99.46 ± 0.20) ％,respectively (all RSDs≤0.87％,n=3).CONCLUSIONS:Prepared DODT are all in line with the quality requirements of orally disintegrating tablets.
ABSTRACT
OBJECTIVE:To develop a method for rapid,accurate and simultaneous determination of dexzopiclone,zolpidam and zaleplon in human plasma. METHODS:After the plasma sample was processed by liquid-liquid extraction,UPLC-MS/MS was established to detect plasma sample with carbamazepine as internal standard. The separation was performed on a Waters ACQUITY UPLC HSS T3 column with mobile phase composed of 0.1% ammonium solution-acetonitrile (gradient elution) at flow rate of 0.2 ml/min. The column temperature was set at 40 ℃,and sample size was 5 μl. The detection was performed by multiple reaction monitoring (MRM) via electrospray ionization (ESI) source in positive mode. The mass transition ion-pairs were as follows:m/z 308.2→263.1(zolpidem),m/z 389.3→245.0(dexzopiclone),m/z 306.2→236.1(zaleplon),m/z 237.3→151.2(internal standard). RE-SULTS:The linear range of zolpidem,dexzopiclone and zaleplon were 0.02-20.00,0.50-20.00,0.02-20.00 ng/ml,respectively (r=0.990 1,0.996 8,0.991 7). LLOQ of them were 0.02,0.50,0.02 ng/ml,and detection limit were 0.01,0.20,0.01 ng/ml. RS-Ds of intra-day and inter-day were all lower than 15% ;extraction recovery were 88.9% -106.5% ;matrix effect were 94.8%-106.3%. CONCLUSIONS:The method is simple,rapid,sensitive and specific,and it can be used for simultaneous deter-mination of zaleplon,zolpidem and dexzopiclone in human plasma.