ABSTRACT
Objective:To investigate whether memantine hydrochloride (MEM) could promote the bactericidal effect of neutrophils against methicillin-resistant Staphylococcus aureus (MRSA) and the possible mechanism. Methods:Neutrophils were co-incubated with different concentrations of MEM and MRSA for 4 h. Then the cell lysates were collected and cultured on plate for survival bacteria counting. After co-incubation, the neutrophils were collected to detect the production of reactive oxygen species (ROS) and the release of neutrophil extracellular traps (NETs). A mouse model of MRSA infection was established, and then the mice were treated with or without MEM. Blood, spleen and kidney samples were collected from the mice for bacterial colony counting and blood procalcitonin (PCT) detection. In the 48 h survival experiment, the mice were first infected with MRSA, and then treated with MEM or PBS. The survival rates of the mice were calculated and the survival curves were drawn.Results:The number of MRSA co-cultured with neutrophils decreased significantly in the presence of MEM, and within a certain concentration range, the survival number of MRSA decreased with the increase of MEM concentration. Moreover, MEM could significantly promote the production of ROS by neutrophils and the formation of NETs. In vivo experiment showed that the concentration of PCT in mouse blood samples was lower in the MRSA+ MEM group than in the MRSA+ PBS group. The animal experiment also revealed that MEM significantly decreased the bacteria loads in mouse blood and organs and increased the 48 h survival rate after MRSA infection.Conclusions:MEM could significantly promote the bactericidal effect of neutrophils against MRSA, which might be related to the enhanced generation of ROS by neutrophils and the formation of NETs.
ABSTRACT
Objective To investigate the efficacy and safety of rosuvastatin combined with memantine hydrochloride in the treatment of vascular dementia.Methods Sixty-six patients with vascular dementia admitted to the Hospital of Zhejiang Provincial Armed Police Force and Haining Kanghua Hospital from January 2016 to January 2018 were enrolled.According to the digital table,the patients were divided into the observation group and the control group,with 33 cases in each group.Both two groups were given routine treatment.The control group was treated with rosuvastatin,and the observation group was given rosuvastatin combined with memantine hydrochloride.Both two groups were treated for 12 weeks.The ADL score and MoCA score,oxidative stress index,inflammatory factor,cerebral kinetic index changes,clinical efficacy and adverse reactions after treatment were compared between the two groups.Results The therapeutic effect of the observation group was 87.88％ (29/33),which was significantly higher than 63.64％ (21/33) of the control group (x2 =5.280,P =0.022).After treatment,the ADL,MoCA,SOD levels,Vmax and BHI of the observation group were (41.26 ± 5.37) points,(24.23 ± 1.71) points,(112.27 ± 15.35) μU/L,(65.15 ± 11.75) cm/s,(0.79 ± 0.36),respectively,which were higher than those of the control group [(36.19 ± 4.07) points,(20.25 ± 1.46) points,(93.84 ± 12.76) μU/L,(59.15 ± 11.74) cm/s,(0.58 ± 0.26)],the differences were statistically significant (t =4.322,10.168,5.304,2.075,2.846,all P ＜ 0.05).The levels of MDA,HCy,TNF-α,IL-6 and IL-1β in the observation group were (6.37 ± 1.05) μmol/L,(31.36 ± 9.59) μmol/L,(184.15 ± 15.12) ng/L,(229.85 ± 27.69) ng/L,(127.64 ± 17.86) ng/L,respectively,which were lower than those in the control group [(7.32 ± 1.07) μmol/L,(42.27 ± 11.34) μmol/L,(208.72 ± 15.26) ng/L,(262.75 ± 25.64) ng/L,(148.75 ± 18.64) ng/L],the differences were statistically significant (t =3.640,4.220,6.570,5.008,4.698,all P ＜ 0.05).There was no statistically significant difference in the incidence of adverse reactions between the two groups (P ＞ 0.05).Conclusion The clinical efficacy of rosuvastatin combined with memantine hydrochloride in the treatment of patients with vascular dementia can significantly reduce oxidative stress and inflammatory response,improve cerebral hemodynamics and cognitive function,and improve patients' quality of life.
ABSTRACT
Objective@#To investigate the efficacy and safety of rosuvastatin combined with memantine hydrochloride in the treatment of vascular dementia.@*Methods@#Sixty-six patients with vascular dementia admitted to the Hospital of Zhejiang Provincial Armed Police Force and Haining Kanghua Hospital from January 2016 to January 2018 were enrolled.According to the digital table, the patients were divided into the observation group and the control group, with 33 cases in each group.Both two groups were given routine treatment.The control group was treated with rosuvastatin, and the observation group was given rosuvastatin combined with memantine hydrochloride.Both two groups were treated for 12 weeks.The ADL score and MoCA score, oxidative stress index, inflammatory factor, cerebral kinetic index changes, clinical efficacy and adverse reactions after treatment were compared between the two groups.@*Results@#The therapeutic effect of the observation group was 87.88%(29/33), which was significantly higher than 63.64%(21/33) of the control group (χ2=5.280, P=0.022). After treatment, the ADL, MoCA, SOD levels, Vmax and BHI of the observation group were (41.26±5.37)points , (24.23±1.71)points, (112.27±15.35)μU/L, (65.15±11.75)cm/s, (0.79±0.36), respectively, which were higher than those of the control group [(36.19±4.07)points, (20.25±1.46)points, (93.84±12.76)μU/L, (59.15±11.74)cm/s, (0.58±0.26)], the differences were statistically significant (t=4.322, 10.168, 5.304, 2.075, 2.846, all P<0.05). The levels of MDA, HCy, TNF-α, IL-6 and IL-1β in the observation group were (6.37±1.05)μmol/L, (31.36±9.59)μmol/L, (184.15±15.12)ng/L, (229.85±27.69)ng/L, (127.64±17.86)ng/L, respectively, which were lower than those in the control group [(7.32±1.07)μmol/L, (42.27±11.34)μmol/L, (208.72±15.26)ng/L, (262.75±25.64)ng/L, (148.75±18.64)ng/L], the differences were statistically significant (t=3.640, 4.220, 6.570, 5.008, 4.698, all P<0.05). There was no statistically significant difference in the incidence of adverse reactions between the two groups (P>0.05).@*Conclusion@#The clinical efficacy of rosuvastatin combined with memantine hydrochloride in the treatment of patients with vascular dementia can significantly reduce oxidative stress and inflammatory response, improve cerebral hemodynamics and cognitive function, and improve patients’ quality of life.
ABSTRACT
OBJECTIVE: To investigate the effects of memantine hydrochloride on cognitive function, cerebral hemodynamics and oxidative stress level in patients with vascular dementia (VD). METHODS: A total of 70 VD patients in the Third Affiliated Hospital of Xinxiang Medical College from Feb. 2013 to Feb. 2015 were divided into control group (36 cases) and observation group (34 cases) aoccording to random number table. Observation group was given Memantine hydrochloride tablets orally with initial dose of 5 mg/d, qd, increasing by 5 mg/week gradually, maintaining at 20 mg/d, qd, at 4th week. Control group was given Piracetam tablets 0. 8 g orally, tid. A treatment course of 2 groups lasted for 4 weeks, and both were treated for 6 courses. Clinical efficacies as well as MoCA scores, ADL scores, systolic peak velocity (Vmax),diastolic peak velocity (Vmin),pulsatility index (PI), resistance index (RI) and breath holding index (BHI) of middle cerebral artery, the levels of MDA, SOD and Hcy were observed in 2 groups. The occurrence of ADR was recorded. RESULTS: Four, two patients withdrew from the study in control and observation group, respectively, and 32 patients in each group completed the study. The total response rate of observation group was 87. 50％, which was significantly higher than 65. 63％ of control group, with statistical significance (P＜0. 05). Before treatment, there was no statistical significance in above indexes between 2 groups (P＞0. 05). After treatment, MoCA, ADL scores and SOD levels of 2 groups were increased significantly, while MDA and Hcy levels were decreased significantly; Vmax and BHI of observation group were increased significantly, and above indexes of observation group was significantly better than those of control group, with statistical significance (P＜0. 05). There was no statistical significance in Vmin, PI or RI between 2 groups before and after treatment, and Vmax or BHI of control group before and after treatment (P＞0. 05). ADRs of 2 groups were mild, and there was no statistical significance in the incidence of ADR between 2 groups (P＞0. 05). CONCLUSIONS: Memantine hydrochloride in the treatment of VD patients can improve the cerebral hemodynamics, reduce oxidative stress and improve cognitive function with good safety.
ABSTRACT
Objective: To optimize the formula of memantine hydrochloride sustained release pellets and investigate the drug release in vitro.Methods: Memantine hydrochloride sustained release pellets were prepared by a fluidized bed.The factors such as inlet air temperature, spray pressure and feeding rate were optimized by orthogonal tests.The Box-Behnken response surface methodology was used to screen the major influencing factors (ethyl cellulose aqueous dispersion, PEG 6000 and the coating weight) in the release of memantine hydrochloride.The coating formula and coating weight were optimized with the cumulative release rate of memantine hydrochloride in 2, 6,and 12 h as the response values.The drug release in vitro was also studied.Results: The optimum preparation parameters of the pellets were as follows: the inlet air temperature of 45℃, the spray pressure of 1.0 bar, and the feeding rate of 1.5 r·min-1.The best sustained release coating formula was as follows: the content of ethyl cellulose aqueous dispersion of 8.4%, the content of PEG 6000 of 2.3%, and the weight gain of sustained release layer of 16.7%.The memantine hydrochloride sustained release pellets had notable sustained release effect.Conclusion: Orthogonal tests and Box-Behnken response surface method can be used for the formula optimization of memantine hydrochloride sustained-release pellets.The established fitting model is simple with good predictability.
ABSTRACT
Objective: To establish a GC method for the determination of content and content uniformity of memantine hydrochloride dispersible tablets.Methods: The sample was dissolved in water, alkalified by sodium hydroxide solution and extracted by methylene chloride.An HP-5 gas chromatography column (50 m×0.32 mm, 1.05 μm) was used.The column temperature was programming increased, and the initial temperature maintained at 120 ℃ for 3 min, and then raised to 220 ℃ at a rate of 10℃·min-1 and maintained for 7 min.A hydrogen flame ionization detector (FID) was used and the split ratio was 1∶1.The inlet temperature was 230 ℃ and the detector temperature was 260 ℃.The injection volume was 1 μl and the carrier gas was nitrogen with high purity at a flow rate of 3.0 ml·min-1.Adamantane was used as the internal standard, and the internal standard method was used for the calculation.Results: The calibration curve was linear over the range of 0.05-1.0 mg·ml -1 (r=0.999 7).The detection limit and the limit of quantification was 1.1 ng and 3.3 ng, respectively.The average recovery was 100.2% (RSD =0.73%, n=9).Conclusion: The method has the advantages of simple operation, small extraction process toxicity, little environmental pollution, high accuracy and high specificity, and can be used for the determination of content and content uniformity of memantine hydrochloride dispersible tablets.
ABSTRACT
OBJECTIVE:To investigate the clinical efficacy and safety of Memantine hydrochloride tablets combined with Tianzhi granules in the treatment of vascular dementia. METHODS:A total of 94 patients with vascular dementia selected from our hospital during Jun. 2014-Jun. 2016 were divided into observation group and control group according to random number table,with 47 cases each. Besides basic therapy,control group was given Tianzhi granules 5 g,po,tid. Observation group was additionally given Memantine hydrochloride tablets with initial dose of 5 mg,increasing by 5 mg every week,maintaining dose of 20 mg/d at 4th week,po,qd,on the basis of control group. Both groups received treatment for consecutive 4 weeks. Clinical efficacies as well as MMSE,MoCA,ADL scores,the levels of brain-derived neurotrophic factor(BDNF),malondialdehyde(MDA)and super-oxide dismutase(SOD)before and after treatment were observed in 2 groups.The occurrence of ADR was recorded.RESULTS:To-tal response rate of observation group(80.85%)was significantly higher than control group(61.70%),with statistical significance (P<0.05). Before treatment,there was no statistical significance in MMSE,MoCA,ADL scores,the levels of BDNF,MDA or SOD between 2 groups(P>0.05).After treatment,MMSE,MoCA,ADL scores,the levels of BDNF and SOD in 2 groups were increased significantly,while MDA level was decreased significantly;observation group was significantly better than control group,with statistical significance(P<0.05). No obvious ADR was found in 2 groups. CONCLUSIONS:Memantine hydrochlo-ride tablets combined with Tianzhi granules in the treatment of vascular dementia show significant therapeutic efficacy,and can im-prove cognitive function,daily living activity and BDNF,MDA and SOD levels of patients with good safety.
ABSTRACT
OBJECTIVE:To investigate the clinical efficacy and safety of Memantine hydrochloride tablets combined with Tianzhi granules in the treatment of vascular dementia. METHODS:A total of 94 patients with vascular dementia selected from our hospital during Jun. 2014-Jun. 2016 were divided into observation group and control group according to random number table,with 47 cases each. Besides basic therapy,control group was given Tianzhi granules 5 g,po,tid. Observation group was additionally given Memantine hydrochloride tablets with initial dose of 5 mg,increasing by 5 mg every week,maintaining dose of 20 mg/d at 4th week,po,qd,on the basis of control group. Both groups received treatment for consecutive 4 weeks. Clinical efficacies as well as MMSE,MoCA,ADL scores,the levels of brain-derived neurotrophic factor(BDNF),malondialdehyde(MDA)and super-oxide dismutase(SOD)before and after treatment were observed in 2 groups.The occurrence of ADR was recorded.RESULTS:To-tal response rate of observation group(80.85%)was significantly higher than control group(61.70%),with statistical significance (P<0.05). Before treatment,there was no statistical significance in MMSE,MoCA,ADL scores,the levels of BDNF,MDA or SOD between 2 groups(P>0.05).After treatment,MMSE,MoCA,ADL scores,the levels of BDNF and SOD in 2 groups were increased significantly,while MDA level was decreased significantly;observation group was significantly better than control group,with statistical significance(P<0.05). No obvious ADR was found in 2 groups. CONCLUSIONS:Memantine hydrochlo-ride tablets combined with Tianzhi granules in the treatment of vascular dementia show significant therapeutic efficacy,and can im-prove cognitive function,daily living activity and BDNF,MDA and SOD levels of patients with good safety.
ABSTRACT
Objective:To prepare sustained-release pellets of memantine hydrochloride and investigate the in vitro drug release be-havior. Methods:The drug-loaded pellets were prepared by a fluid bed coating technology, the sustained-release pellets were prepared with Eudragit RL 30D and Eudragit RS 30D as the coating materials, and in vitro drug release behavior of the sustained-release pellets was studied. Results:The in vitro drug release was steady and complete in 24h, which fit a zero-order kinetics model. Conclusion:The memantine hydrochloride sustained-release pellets has the sustained-release property.