缓释制剂辅料导致盐酸二甲双胍降解产生N-亚硝基二甲胺的影响因素研究

选取高效液相色谱-质谱作为检测方法,利用具有降解作用的氧化剂进行干预,同时针对溶剂与氧化剂的加入量进行调整与控制。通过实验,了解缓释制剂辅料添加量、加热时间、温度等因素变化情况,并评估NDMA生成量。结果表明,缓释制剂中硫酸钾、次氯酸钠具有协同氧化作用,二者协同反应后,可促使盐酸二甲双胍降解成NDMA。通过选择低温度氧化剂辅料、控制温度与时间指标,能够减少NDMA生成。若将残留氧化剂作为辅料,则要求考虑安全性指标,期间做好质量控制工作,提高辅料质量监控水平,重视辅料之间相溶性。

盐酸二甲双胍混合材料骨架缓释片的研制与功能性分析

目的:分析二甲双胍混合材料骨架缓释片的研制方法与功能性。方法:本药品研制使用EC作为骨架材料,完成对盐酸二甲双胍骨架缓释片的制作,通过实验分析影响释药的因素,如EC规格、黏合剂类型、润滑剂添加量、技术工艺、释放介质pH。根据上述研究结果,对处方进行筛选,由此选取最佳的二甲双胍混合材料缓释片的研制、介绍药品功能性。结果:盐酸二甲双胍骨架混合材料缓释片的体外释药满足回归方程,EC规格、制片压力对盐酸二甲双胍释放造成的影响小,而黏合剂种类、润滑剂用量与制片工艺对药物释放造成的影响大。结论:以二甲双胍混合材料为骨架,添加其他辅料研制出的缓释片具有良好功能性,缓释片的释放速率适当,并且工艺简单、安全性较高。

清末民初中小学价值观教育的传承与变革

中国传统儿童价值观教育历经几千年的历史积淀,形成了较为完整的内容体系。这一体系中有积极、合理的成份,也存在消极、糟粕的东西,这为清末民初中小学传统价值观教育的传承与变革创造了重要的文化条件。清末民初中小学价值观教育在近代中国文化变革的背景下,传承了“以孝为先”“忠恕之道”及注重个人品德修养的传统价值观教育优良传统,也摒弃了愚忠、愚孝的腐朽教育内容,同时吸收了西方近代公义、公德、权利平等、遵守法律等德育元素。清末民初中小学价值观教育的传承与变革一方面深受儒家道德与教育传统的影响,当新的价值观教育思想与实践产生时,传统儒家道德与教育传统依然根深蒂固。另一方面,清末民初的西学东渐引起了中国传统文化的异动,而文化异动与价值观变迁在很大程度上促进了中小学价值观教育的传承与变革。此外,近代先进思想家、教育家对中国传统道德和文化理念的反思以及对西方道德与文化的审视也推动了中小学价值观教育的传承与变革。

B-矩阵线性互补问题误差界的新估计式

给出了严格对角占优M-矩阵及逆矩阵之间元素的关系式,得到了严格对角占优M-矩阵的逆矩阵的无穷大范数的新上界,结合新界和不等式放缩技巧得到B-矩阵线性互补问题误差界的新估计式,改进了已有的结果.同时,理论证明及数值算例表明了新估计式的有效性.

柴归颗粒对慢性不可预知温和刺激抑郁大鼠模型肠道菌群的作用

目的利用16S rRNA高通量测序技术研究柴归颗粒对慢性不可预知温和刺激(chronic unpredicted mild stress,CUMS)抑郁大鼠模型肠道菌群的调节作用,探讨柴归颗粒的抗抑郁作用及机制。方法SD大鼠随机分为对照组、模型组和柴归颗粒(8.3 g/kg)组,给药1 h后造模,持续28 d。收集大鼠肠道内容物,提取总DNA,根据细菌16S rRNA V3~V4区设计引物进行扩增,利用Illumina Miseq平台进行高通量测序。结果与对照组比较,模型组大鼠肠道菌群栖热菌门(Thermi)、变形菌门(Proteobacteria)、拟杆菌门(Bacteroidetes)和放线菌门(Actinobacteria)相对丰度水平显著降低(P<0.05),乳酸杆菌属Lactobacillus相对丰度水平显著升高(P<0.05),栖热菌属Thermus、不动杆菌属Acinetobacter、甲基杆菌属Methylobacterium、青枯菌Ralstonia、纤毛菌属Leptothrix、假单胞菌属Pseudomonas、棒状杆菌属Corynebacterium和苍白杆菌属Ochrobactrum相对丰度水平显著降低(P<0.05)。与模型组比较,柴归颗粒可调节CUMS大鼠肠道菌群的构成,显著回调栖热菌门、变形菌门、拟杆菌门和放线菌门相对丰度水平(P<0.05、0.01),显著降低乳酸杆菌属相对丰度水平(P<0.01),显著升高栖热菌属、不动杆菌属、甲基杆菌属、青枯菌属、纤毛菌属和苍白杆菌属相对丰度水平(P<0.01)。结论柴归颗粒可能通过调节参与精氨酸代谢途径的肠道菌群发挥抗抑郁作用。

肠道菌群在中药抗抑郁作用中的研究进展

抑郁症是一种常见的情感性精神障碍,患者不仅在情绪上表现出持续的低落、悲观、冷漠等,同时在躯体上常伴有食欲不振、便秘等胃肠道症状。肠道菌群在抑郁症发病机制中潜在的生物学作用已受到广泛关注,其在肠与脑相互作用中扮演着重要角色,不仅影响肠道屏障功能,还可以通过调控肠道微生物-肠-脑轴维持宿主机体的稳态。近年来,中药在预防和治疗抑郁症等神经精神系统疾病时,具有效果显著且不良反应较小的特点,且中药通过调节肠道菌群结构、减少移位以及维持菌群正常功能等方面发挥抗抑郁作用的研究已被广泛关注。本综述主要通过调研近年来相关文献资料,从中药单体、单味药及复方多种角度探讨中药对肠道菌群的改善作用,从中药对肠道菌群结构的矫正作用、调节免疫作用、进行菌群移植以及对其代谢物调节等不同层次发挥抗抑郁的作用及其机制进行由浅入深的总结。本综述将为深入阐释肠道菌群在抑郁症的发生机制及中药抗抑郁的作用机制研究提供依据。

中药制剂前物料的性质体系及其表征技术研究

中药制剂现代化进程中面临诸多挑战,中药粉末、中药提取物和中药组分作为中药制剂前最具有代表性的3类物料,其性质是指导中药制剂剂型设计的核心基础。本团队在长期研究中药制剂物料性质的基础上,根据中药制剂物料在一定条件所处的状态及物质之间相互作用特点,构建了中药制剂物料的性质体系,由物质构成、空间构造、体性质、面性质及理化性质5大类18小类构成,并进一步建立了相应的指标体系,包含61项指标及表征技术,为中药制剂的现代化奠定基础。

Auricular acupressure as assistant in primary insomnia management: a randomized single-blind controlled clinical trial

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 in clusi on criteria were en rolled in a ran domized con trolled 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 PvO.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 PvO.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). Con elusion: Dexzopicl one plus auricular acupressure is effective and safe for pati ents with primary in somnia both in short and long terms, and it is more effective tha n mono therapy of dexzopicl one.

基于中药提取物粒子空间构造性质与吸湿性关联的抗吸湿技术研究

探究中药提取物空间构造性质与吸湿性的相关性及抗吸湿技术。以茯苓提取物为模型药物,在中药提取物流浸膏中加入不同比例的预胶化淀粉及微晶纤维素,利用不同干燥工艺制造不同空间构造的粉体粒子。用平衡吸湿率(F^(∞))及半吸湿时间(t_(1/2))表征其吸湿行为,采用偏最小二乘法分析各粉体的吸湿性与粒径(D_(90))、孔隙率(ε)、真密度(ρ_(t))、表面元素分布等空间构造性质的相关性。3种干燥方法所制备的茯苓提取物的F^(∞)喷雾>常压>减压;t_(1/2)减压>常压>喷雾。喷雾干燥所得粉体呈现球形结构,粒径和粒子内ε最小,吸湿性较强。减压干燥粉体表面元素大量富集效应有效降低了粉体的吸湿性。F^(∞)、t_(1/2)分别与ε呈负相关,与D_(90)呈正相关,各空间构造性质的交互影响不显著。中药提取物粉体粒子的空间构造与吸湿性存在相关性,通过设计空间构造可以改善吸湿性,该研究为中药制剂的防潮技术提供了一定的实践依据。

中药提取物吸湿性的动态二维表征技术及影响因素分析

构建中药提取物吸湿性的动态二维表征技术及探究粉体的物料性质对吸湿性的影响。以丹参提取物、枳壳提取物、茯苓提取物与不同比例的可溶性淀粉、无水乳糖、微晶纤维素的药辅混合粉体作为研究对象,在25℃及75%湿度为标准的条件下,测定各粉体的吸湿率-时间动态曲线,并推导出半平衡吸湿时间(t_(1/2))及平衡吸湿率(F^(∞))构成二维评价指标,最后运用主成分分析法(PCA)以及偏最小二乘分析法(PLS)分析各物料性质与吸湿行为的相关性。结果表明,以1/t_(1/2)=0.1 h^(-1)、F^(∞)=15%为中心构建的吸湿性动态二维表征体系可将中药提取物粉体的吸湿行为分为吸湿量大吸湿快、吸湿量大吸湿慢、吸湿量小吸湿快、吸湿量小吸湿慢4类,且吸湿量与D_(50)、D_(90)、ρ_(b)、ρ_(t)呈负相关;吸湿速率与D_(10)、D_(50)、D_(90)、ρ_(b)、ρ_(t)呈负相关,与含水量呈正相关。本研究所构建的中药提取物吸湿性动态二维表征指标与中药提取物(CMEs)的物性相匹配,该表征技术具有可行性及科学性,动态多维表征的思路及方法具有较强的推广价值。

Efficacy and safety of electroacupuncture for perimenopausal insomnia: a randomized controlled trial

Objective: To observe the effectiveness and safety of electroacupuncture (EA) plus Luohua Anshen oral liquid for patients with perimenopausal insomnia. Methods: A total of 66 participants who met the inclusion criteria were enrolled in the randomized controlled trial and allocated to a treatment group and a control group at a ratio of 1:1, with 33 cases in each group. Both groups were given Luohua Anshen oral liquid as a basic treatment. The treatment group was additionally given EA every other day, three times a week. Both groups were treated for four weeks and a four-week follow-up was conducted. The scores of Pittsburgh sleep quality index (PSQI), Kupperman index (KI) and traditional Chinese medicine sleep syndrome scale (TCMSSS) were recorded at pre- and post-treatment, and at the follow-up. Meanwhile, adverse effects were monitored and recorded. Results: After four-week treatment, the global scores of PSQI, KI and TCMSSS in both groups declined significantly (all P<0.05), and the decreases in the treatment group were more significant than those in the control group (allP<0.05). The global scores of PSQI, KI and TCMSSS in both groups at the follow-up visit were significantly different from the corresponding baseline (allP<0.05), while insignificantly different from those assessed at post-treatment (allP>0.05). The total effective rate was 93.9% in the treatment group, significantly higher than 72.2% in the control group (P<0.05). No significant adverse event was reported in this trial excepted one patient experienced slight dizziness in the first acupuncture treatment. Conclusion: EA plus Luohua Anshen oral liquid is safe for perimenopausal insomnia with satisfactory short- and long-term effectiveness, and it shows certain advantage compared with using Luohua Anshen oral liquid alone.

Discussion of the promising effect of electroacupuncture on cognitive improvement in D-galactose-induced aging rats based on NLRP3-ASC-Caspase-1 signaling pathway

Objective:To investigate the effect of electroacupuncture(EA)on cognitive function in D-galactose(D-gal)-induced aging rats,and the correlation between the effect and nucleotide-binding oligomerization domain(NOD)-like receptor protein 3(NLRP3)-ASC-Caspase-1 signaling pathway.Methods:Forty-six male Sprague-Dawley(SD)rats were randomly divided into a control group(n=10),a model group(n=12),an EA-7 d group(n=12)and an EA-21 d group(n=12).Except the control group,the other three groups received 42 consecutive days of intraperitoneal injection of D-gal to establish aging rat models with cognitive dysfunction.The control group received the same amount of normal saline via intraperitoneal injection.Two EA groups were given EA therapy for 21 consecutive days(began from the 22nd day of modeling)or 7 consecutive days(began from the 36th day of modeling)accordingly at Dazhui(GV 14),Baihui(GV 20),Shenshu(BL 23)and Zusanli(ST 36).After modeling/intervention,all four groups received behavioral evaluations by Morris water maze(MWM)test,novel object recognition(NOR)test and step-down passive avoidance(SDPA)test followed by the Western blot(WB)detection of the expression levels of hippocampal NLRP3 inflammasome-associated proteins NLRP3,ASC and Caspase-1.Results:MWM(place navigation test,PNT)results showed that the escape latency in the model group was significantly longer than that in the other three groups(P<0.05),and there was no significant difference among the other three groups on the 1st day of the test(P>0.05).From the 2nd day to the 4th day of the test,there was no significant difference between the EA-21 d group and the control group(P>0.05)in the escape latency;the escape latency was significantly shorter in the EA-21 d group than in the model group and the EA-7 d group(P<0.05).MWM(spatial probe test,SPT)results showed that the time spent in the target quadrant was significantly shorter and platform crossover number was significantly lower in the model group than in the other three groups(P<0.05).The time spent in the target quadrant was longer in the EA-7 d group than in the model group(P<0.05),but was shorter than that in the control group and the EA-21 d group(P<0.05).There was no significant difference in the swimming speed among the four groups(P>0.05).NOR results showed that there was no significant difference in the recognition ratio between the EA-7 d group and the EA-21 d group(P>0.05),and the recognition ratio was significantly higher in the two EA groups than in the model group(P<0.05),but was lower than in the control group(P<0.05).SDPA results showed that the electric shock number was higher in the model group than in the other three groups(P<0.05),and the differences among the other three groups were statistically insignificant(P>0.05).The model group had the shortest step-down latency,followed by the EA-7 d group,the EA-21 d group and the control group in order(P<0.05).The WB results indicated that the expression level of NLRP3 was significantly lower in the control group and the EA-21 d group than in the model group and the EA-7 d group(P<0.05).The expression levels of ASC and Caspase-1 were significantly higher in the model group than in the other three groups(P<0.05),and there was no significant difference among these three groups(P>0.05).Conclusion:NLRP3 inflammasome may be involved in the development of cognitive decline in aging rats;7 consecutive days of EA intervention can partially improve the cognitive impairment in aging rats though the effect is rather limited;21 consecutive days of EA intervention may improve the learning and memory abilities in aging rats via downregulating the expression levels of NLRP3 inflammasome-associated proteins in hippocampus.

Effects of electroacupuncture on the behaviors and expressions of hippocampal neurotransmitters and Bax/Bcl-2 proteins in rat models of anxiety disorder

Objective:To investigate the effects of electroacupuncture(EA)on the behaviors of rat with anxiety disorder,and the expressions of hippocampal neurotransmitters including 5-hydroxytryptamine(5-HT),norepinephrine(NE)and dopamine(DA),and the expressions of hippocampal B-cell lymphoma-2(Bcl-2)and Bcl-2 associated X(Bax).Methods:Forty-six male Wistar rats were randomly divided into a control group(n=10);a model group(n=12),an EA group(n=12),and a drug group(n=12).Except the control group,the other three groups were established into rat models of anxiety disorder using uncertain empty bottle stimulation.Rats in the EA group and the drug group received corresponding interventions for 15 consecutive days[EA group was given EA at Baihui(GV 20)and Sanyinjiao(SP 6);the drug group was given aqueous solution of alprazolam via intragastric administration].After intervention,all four groups received open-field test(OFT)and elevated plus-maze(EPM)for behavioral evaluations.The expressions of 5-HT,NE and DA in hippocampus were determined by fluorescence spectroscopy(FS)while the expressions of Bcl-2 and Bax proteins in hippocampus were determined by Western blot(WB).Results:The OFT horizontal scores in the control group,EA group and drug group were significantly higher than that in the model group(all P<0.05),and the difference between the EA group and the drug group was statistically insignificant(P>0.05);the OFT vertical scores in the model group,EA group and drug group were significantly lower than the score in the control group(all P<0.05).The EPM percent of open-arm entries(OE%)in the control group,EA group and drug group was higher than that in the model group(P<0.05),and the differences among these three groups were statistically insignificant(P>0.05);though the percent of open-arm total time(OT%)in the EA group was lower than that in the control group(P<0.05);the difference was statistically insignificant when compared with the drug group(P>0.05),and it was significantly higher than that in the model group(P<0.05).The expression of 5-HT in the EA group was higher than that in the control group(P<0.05);the expression of 5-HT in the EA group was significantly lower than that in the model group(P<0.05);the difference between the EA group and the drug group was statistically insignificantly(P>0.05).The expression of NE in the model group was significantly higher than that in the other three groups(P<0.0S),and there was no significant difference among these three groups(P>0.05).The expression of DA in the EA group was significantly higher than that in the control group and the drug group(both P<0.05),while the difference between the EA group and the model group was statistically insignificant(P>0.05).The expression of Bax in the model group was significantly higher than that in the other three groups(all P<0.05),whereas the expression of Bcl-2 in the model group was significantly lower than that in the other three groups(all P<0.05),and the differences in both Bax and Bcl-2 among the other three groups were statistically insignificant(all P>0.05).Bax/Bcl-2 in the EA group was significantly higher than that in the control group(P<0.05)and lower than that in the model group(P<0.05),and the difference was statistically insignificant when compared with the drug group(P>0.05).Conclusion:EA shows promising effects in attenuating rats'anxiety disorder,which may be achieved by the down-regulation of the expressions of 5-HT and NE in the hippocampus and/or inhibition of hippocampal neuronal apoptosis.The efficacy is comparable to that of intervention with alprazolam.

Memory response to manual acupuncture in chronic insomniacs: evidence from event-related potentials

Objective:To investigate the effectiveness and safety of manual acupuncture for memory loss and sleep quality in chronic insomniacs.Methods:A total of 60 eligible participants were enrolled and randomized into either a treatment group or a control group,with 30 cases in each group.The treatment group was intervened by manual acupuncture whereas the control group was given sham acupuncture.In the two groups,the interventions were offered once every other day and three times a week,for 8 weeks in total.Before and after the treatment,Pittsburgh sleep quality index (PSQI) and eventrelated potentials (ERPs) were used to assess the patients' sleep quality and memory,respectively.Meanwhile,adverse events were monitored and recorded.Results:After 8-week treatment,both the treatment group and the control group showed a significant decrease in the PSQI global score (P<0.001,P<0.01),and the decrease in the treatment group was more significant than that in the control group (P<0.001).The intra-group comparisons of ERPs indicated that,the latencies of N1 and P3 were shortened and the amplitudes of N1 and P3 were increased in the treatment group after the intervention,and the differences were statistically significant (P<0.05,P<0.001);in the control group,there were no significant changes in the latency and amplitude after the treatment (P>0.05).The between-group comparisons of ERPs showed that the treatment group was more effective than the control group in shortening the latency of P3 (P<0.01).Conclusion:Acupuncture can be a safe and effective treatment option for chronic insomnia coupled with memory impairment.