以丙戊酸钠为基础的抗癫痫联合用药在病因不明的Lennox-Gastaut综合征患儿中的应用

目的观察以丙戊酸钠为基础的抗癫痫联合用药在病因不明的Lennox-Gastaut综合征患儿中的应用效果。方法采用临床随机、对照的方式,选择2013年8月至2016年2月在我院诊治的病因不明的LennoxGastaut综合征患儿84例,根据随机信封抽签原则分为观察组与对照组,每组42例,对照组给予口服拉莫三嗪治疗,观察组在对照组治疗的基础上给予口服丙戊酸钠治疗,两组均观察3个月。结果观察组的总有效率高于对照组(95.2%vs.88.1%,P<0.05)。观察组的不良反应发生率低于对照组(9.5%vs.38.1%,P<0.05)。两组治疗前后组间、组内的血清FT4、TSH含量比较差异均无统计学意义(P>0.05)。治疗后,观察组的主动肌张力、被动肌张力、行为能力评分分别为12.98±0.98、7.54±0.65、7.61±0.65,明显高于对照组(10.35±0.67、7.02±0.45、6.61±0.78),差异有统计学意义(P<0.05)。结论以丙戊酸钠为基础的抗癫痫联合用药对病因不明的Lennox-Gastaut综合征患儿的甲状腺激素的表达无明显影响,可提高疗效,减少不良反应的发生,促进患儿神经行为能力的改善。     

Rufinamide for the treatment of Lennox-Gastaut syndrome

INTRODUCTION: Lennox-Gastaut syndrome (LGS) is a severe treatment-resistant childhood-onset epilepsy. This review examines the role of the new drug rufinamide for the treatment of LGS. AREAS COVERED: MEDLINE and Google Scholar searches were undertaken. The pharmaceutical company was contacted for the latest information. LGS is characterized by the triad of diffuse slow spike-wave discharges in the electroencephalogram (EEG), learning disability (mental retardation) and frequent generalized seizures of multiple types, usually including tonic, atonic and atypical absence seizures. Felbamate, lamotrigine and topiramate have resulted in significant reductions in some seizure types, but no treatment has achieved acceptable seizure control in most patients. In a pivotal randomized, double-blind, placebo-controlled trial, the new drug rufinamide achieved significant improvements in seizure control in previously resistant subjects when added to up to three concomitant antiepileptic drugs. Open studies including patients with LGS have also demonstrated efficacy. These trials and a large open trial in adults and adolescents with partial seizures have revealed no serious adverse effects so far. The most common adverse events were fatigue/somnolence and vomiting. Rufinamide is of value in decreasing seizure frequency in LGS, but seizure freedom is seldom achieved. Although no serious adverse effects have been identified, the limited data available at present allow no firm conclusions to be drawn with regard to safety. EXPERT OPINION: The data support a role for rufinamide in treating LGS. However, more efforts are required to provide antiepileptic drugs for this treatment-resistant epilepsy syndrome. Rufinamide might also be of value in treating other forms of epilepsy.     

A stability indicating HPLC method for the determination of clobazam and its basic degradation product characterization

Background

Clobazam is used for the treatment of different types of seizure and epilepsy. The present research is undertaken to study the systematic forced degradation of clobazam and to identify its main degradation product under basic conditions.

Methods

The degradation of clobazam was studied under different conditions. Clobazam and its degradation products were separated using a Nova-Pak C18 column and a mixture of KH₂PO₄ 50 mM (pH 8.5) and acetonitrile (50:50, v/v) as the mobile phase with UV detection at 230 nm.

Results

The within-day and between-day precision values in the calibration range of 0.1-20 μg/ml were within 0.5-1.5%. Clobazam was relatively stable in solid from under exposure to visible and UV light and also heat. The clobazam aqueous solution of clobazam was more labile under exposure to visible and UV light. The bulk drug was significantly degraded under exposure to 2 M HCl, 0.1 M NaOH or 3% H₂O₂. Using the tablet powder, higher degradation rates were observed under different stress conditions. The main degradation product of clobazam under basic condition was subsequently characterized.

Conclusion

The developed method could be used for the determination of clobazam in the presence of its degradation products with acceptable precision and accuracy. The applicability of the proposed method was evaluated in commercial dosage forms analysis.     

左乙拉西坦联合托吡酯治疗难治性癫痫综合征的疗效及安全性分析

目的分析左乙拉西坦(LEV)联合托吡酯治疗难治性癫痫综合征的疗效及安全性.方法90例难治性癫痫综合征患儿,根据治疗方法不同分为A组、B组及C组,各30例.A组单纯采用LEV治疗,B组单纯采用托吡酯治疗,C组采用LEV联合托吡酯治疗.比较三组患儿不良反应发生情况及治疗前后韦氏儿童智能量表修订版(WISC-R)评分、头颅磁共振波谱、脑电图棘慢波指数.结果治疗后,三组总智商(FIQ)评分、言语智商(VIQ)评分及领悟评分均显著高于本组治疗前,且C组FIQ评分(107.68±2.55)分、VIQ评分(108.15±3.20)分及领悟评分(15.28±2.70)分均高于A组的(100.20±1.83)、(102.36±2.85)、(13.02±1.50)分和B组的(100.15±1.85)、(102.35±2.88)、(13.00±1.52)分,差异有统计学意义(P<0.05).治疗后,三组NAA/Cr、NAA/Cho+Cr与NAA/Cho均显著高于本组治疗前,且C组高于A组和B组,差异有统计学意义(P<0.05).治疗后,三组NREM期、清醒期脑电图棘慢波指数均显著低于本组治疗前,且C组低于A组和B组,差异有统计学意义(P<0.05).三组不良反应发生率比较差异无统计学意义(P>0.05).结论难治性癫痫综合征患儿接受LEV联合托吡酯治疗可显著提升智力水平,改善脑电波指数,不良反应少,疗效显著、安全性高.     

柳氮磺吡啶片对孤立性直肠溃疡综合征的疗效

目的观察柳氮磺吡啶片(SASP,磺胺类抗菌药)对孤立性直肠溃疡综合征的效果。方法将入选的37例患者随机分为3组:①试验组,给予一般治疗,联合SASP保留灌肠;②对照组,单用SASP保留灌肠;③未用药组,只给予一般治疗;2个疗程后判断疗效。结果基本治愈率:试验组为85.71%,对照组为45.45%,未用药组为25.00%。试验组与对照组比较差异有统计学意义(P<0.05);试验组与未用药组比较差异也有显著性差异(P<0.01)。结论一般治疗联合SASP片剂磨碎后保留灌肠对SRUS治疗效果显著。     

Investigation of an active film coating to prepare new fixed-dose combination tablets for treatment of diabetes

The aim of the present study was to formulate new fixed-dose combination tablets (FCTs) by coating a glimepiride (GLM) immediate-release (IR) layer on a metformin hydrochloride (MTF) extended-release (ER) core tablet using perforated film coating equipment. Composition of GLM-IR coating suspension for homogeneity was studied and application of near-infrared spectroscopy (NIR) to determine the end-point of the coating process was also investigated. The final product was administered to healthy male volunteers and its pharmacokinetic parameters were analyzed. GLM-IR coating suspension was prepared with a ratio of SLS to GLM at 0.75 for homogeneity. An inert mid-layer was introduced to prevent contact between MTF-ER core tablet and GLM-IR layer, which led to an increased release rate of GLM in pH 7.8 medium. The proportional correlation was confirmed between analytical results of GLM determined by NIRS and those by HPLC-UV. Thus, the end-point of the GLM coating process was determined by NIRS, the fast and non-destructive method. New FCTs were confirmed to be bioequivalent to the marketed product.     

氟西汀片治疗灼口综合征临床疗效

目的:观察盐酸氟西汀片治疗灼口综合征(BMS)的临床疗效.方法:选择BMS患者30例,随机分为治疗组15例,口服氟西汀片10mg·d-1,qd,连用6周;对照组15例,口服复合维生素B每日1片,连用6周.治疗前后记录患者疼痛程度和发生频率.结果:治疗组痊愈4例,显效6例,有效3例,总有效率86.6%,与对照组总有效率33.3%相比,差异有显著性(P＜0.01).结论:将灼口综合征视为心身性疾病,应用抗抑郁类药物氟西汀片治疗,疗效显著.然而,停药后的复发情况有待进一步观察.     

Gabapentin enacarbil for the treatment of restless legs syndrome (RLS)

Introduction: Gabapentin enacarbil is a new treatment for restless legs syndrome (RLS). It is a prodrug of the anticonvulsant gabapentin. However, unlike gabapentin, gabapentin enacarbil does not demonstrate saturable absorption. This allows for once-daily dosing and less variability in serum levels.

Areas covered: This review focuses on therapies used to treat RLS, both historical and recent. Data from available trials are summarized, with a particular focus on the efficacy and safety of gabapentin enacarbil. Potential advantages and disadvantages of this therapy in comparison with other RLS treatment modalities are discussed.

Expert opinion: Placebo-controlled trials of gabapentin enacarbil demonstrate considerable efficacy in the treatment of RLS. However, head-to-head trials comparing gabapentin enacarbil with other medications used in the treatment of RLS, including gabapentin, are lacking. Potential advantages with gabapentin enacarbil related to its pharmacokinetic profile are thus difficult to ascertain. Efficacy of gabapentin enacarbil appears comparable with that of the dopamine agonists, long considered the therapy of choice in patients with RLS. Given the lack of direct-comparison trials, and the significant cost differential of gabapentin enacarbil versus established therapies, the drug is likely to be used for patients who have failed other medication trials, or those who experience prolonged symptoms and prefer once-daily dosing.     

Insulin-sensitisers in the treatment of polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is a common endocrine condition with reproductive and metabolic implications. In the current setting there is an evolving, yet inadequate, understanding of the pathophysiology, long-term health implications and ideal therapies for women with PCOS. Insulin resistance, secondary to both genetic and lifestyle factors, is integrally involved in the pathogenesis, the metabolic and clinical features and the long-term sequelae of PCOS in a majority of patients. Therapeutic strategies targeting insulin resistance ameliorate clinical features and may reduce long-term sequelae of PCOS, including diabetes. The main benefit of improved insulin resistance is to improve fertility and potentially to improve clinical features of hyperandrogenism and lower androgen levels. Insulin sensitisers also have the potential to delay the development of diabetes and cardiovascular disease in PCOS. Lifestyle therapy is indicated as the first intervention; however, metformin as an insulin sensitising agent has a role in first-line medical therapy in women with PCOS. Further research is needed to define the role of insulin sensitisers in PCOS and to determine the long-term risks and benefits of these therapies.     

Interactions between modulators of the GABA(A) receptor: Stiripentol and benzodiazepines

Many patients with refractory epilepsy are treated with polytherapy, and nearly 15% of epilepsy patients receive two or more anti-convulsant agents. The anti-convulsant stiripentol is used as an add-on treatment for the childhood epilepsy syndrome known as severe myoclonic epilepsy in infancy (Dravet syndrome). Stiripentol has multiple mechanisms of action, both enhancing GABA_A receptors and reducing activity of metabolic enzymes that break down other drugs. Stiripentol is typically co-administered with other anti-convulsants such as benzodiazepines which also act through GABA_A receptor modulation. Stiripentol slows the metabolism of some of these drugs through inhibition of a variety of cytochrome P450 enzymes, but could also influence their effects on GABAergic neurotransmission. Is it rational to co-administer drugs which can act through the same target? To examine the potential interaction between these modulators, we transiently transfected HEK-293T cells to produce α3β3γ2L or α3β3δ recombinant GABA_A receptors. Using whole-cell patch clamp recordings, we measured the response to each benzodiazepine alone and in combination with a maximally effective concentration of stiripentol. We compared the responses to four different benzodiazepines: diazepam, clonazepam, clobazam and norclobazam. In all cases we found that these modulators were equally effective in the presence and absence of stiripentol. The δ-containing receptors were insensitive to modulation by the benzodiazepines, which did not affect potentiation by stiripentol. These data suggest that stiripentol and the benzodiazepines act independently at GABA_A receptors and that polytherapy could be expected to increase the maximum effect beyond either drug alone, even without consideration of changes in metabolism.     

儿童清咽解热口服液治疗小儿急性咽炎（肺胃实热证）的药物经济学评价

目的 通过成本-效果分析,评价儿童清咽解热口服液治疗小儿急性咽炎（肺胃实热证）的经济学优劣。方法 共纳入急性咽炎（肺胃实热证）患儿219例,以2：1：1的比例随机分为试验组、阳性药对照组、安慰剂对照组,在以抗生素为基础治疗的条件下,分别服用儿童清咽解热口服液、蒲地蓝消炎口服液（阳性对照药）、安慰剂,疗程为5 d。选取咽痛疗效、疾病疗效和中医症候疗效作为评价指标,进行成本-效果分析。结果 在咽痛疗效方面,试验组每多获得1个单位的愈显率,比安慰剂组仅需多花费0.62元,比阳性对照组少花费0.54元;在疾病疗效方面,试验组每多获得1个单位的愈显率,比安慰剂组多花费0.57元,比阳性对照组少花费0.54元;在中医证候方面,试验组每多获得1个单位的愈显率,比安慰剂组多花费0.58元,比阳性对照组少花费0.54元。结论 儿童清咽解热口服液联合抗生素治疗小儿急性咽炎（肺胃实热证）,在咽痛症状疗效、疾病疗效和中医症候疗效方面,较蒲地蓝消炎口服液及单独使用抗生素有较优的经济性,与蒲地蓝消炎口服液经济性相当,具有良好的临床应用前景。     

下颌前突综合征X线头影测量特征研究

通过对31例下颌前突综合征患者进行X线头影计算机辅助测量,得出如下特征:(1)上领发育不足,面中部凹陷或扁平。(2)下颌骨向前下方过度生长,Angle分类为Ⅲ型,面下1/3前突,前牙反合或开合。(3)下颌过陡,面部垂直高度变长。(4)下颌切牙呈代偿性内倾。(5)下唇高变长。认为X线头影测量是以数量化方法指导手术方案的制定。     

Design and evaluation of bilayered buccal film preparations for local administration of lidocaine hydrochloride

Bilayered oromucosal film preparations (buccal films) offer a promising way to enable drug administration via the oral cavity. Adding a non-soluble or slowly eroding/dissolving backing layer to a mucoadhesive drug-loaded layer enables unidirectional drug delivery.The aim of this study was to investigate different approaches to the manufacture of bilayered films and to examine their properties by applying different characterization methods including an optimized experimental setup for the study of drug release from bilayered films. A solvent suitability study was performed screening over 15 polymers with respect to their feasibility for viscous film formation for film preparation by solvent casting method. Two methods (double-casting and pasting) were found as suitable methods for bilayered film manufacturing. Results from drug release experiments indicated that slowly eroding hypromellose backing layer films revealed the best shielding of the drug-loaded layer to enable unidirectional drug release. In summary, manufacturing of bilayered films using the described methods was feasible. Furthermore, the use of an optimized experimental setup for drug dissolution studies enabled monitoring of drug release without delays in sampling.     

和胃化湿片治疗腹泻型肠易激综合征的临床研究

目的 研究和胃化湿片治疗腹泻型肠易激综合征(IBS-D)的临床疗效.方法 100例IBS-D患者,按照随机数字抽取法分为对照组及观察组,各50例.对照组给予常规治疗,观察组在对照组的基础上加用和胃化湿片治疗.比较两组患者治疗前后的焦虑自评量表(SAS)评分、抑郁自评量表(SDS)评分、肠易激综合征症状严重程度调查表(I...     

炔雌醇环丙孕酮片治疗多囊卵巢综合征临床分析

目的：探讨炔雌醇环丙孕酮片治疗多囊卵巢综合征（PCOS）的临床效果。方法：选择本院收治的66例多囊卵巢综合征患者,全部PCOS患者都从撤药流血或者月经流血第5天起,每天晚上服用1片炔雌醇环丙孕酮片,连续服用21d。然后在撤药撤血第5天开始重复使用炔雌醇环丙孕酮片,共使用6个周期。观察治疗前后体征参数、性激素水平和血糖代谢水平。结果：多囊卵巢综合征患者在治疗后,多毛体征和痤疮严重程度大为减轻,而且卵巢的体积显著减小,黄体生成素、黄体生成素/空腹胰岛素、总睾酮均显著下降（P〈0.05）,血糖代谢不受影响（P〉0.05）。治疗前正常排卵者3例,治疗后正常排卵者45例。结论：炔雌醇环丙孕酮片对多囊卵巢综合征患者有显著的抗激素作用,对血糖代谢无不良影响,促进排卵,能显著降低雄激素和相关体征。     

二甲双胍联合炔雌醇环丙孕酮片治疗多囊卵巢综合征疗效观察

目的：探讨二甲双胍、炔雌醇环丙孕酮片治疗多囊卵巢综合征的临床效果。方法：收集2009年1月～2010年1月多囊卵巢综合征患者55例,将其随机分为3组,A组18例单独应用二甲双胍500mg/次,每日3次;B组20例单独应用炔雌醇环丙孕酮片,每日1次,每次1片;C组17例炔雌醇环丙孕酮片和二甲双胍联合用药,每组均3个疗程共3个月,于第4个月经周期第2天复查血清促黄体生成素（LH）、促卵泡素（FSH）、睾酮（T）及雌二醇（E2）水平,比较3组治疗前后激素水平变化情况。结果：3组患者治疗前后激素水平有显著差异（P〈0.05）,C组治疗前后激素水平变化与A组及B组比较差异明显（P〈0.05）。结论：二甲双胍联合炔雌醇环丙孕酮片能有效纠正高雄激素血症,达到治疗多囊卵巢综合征的效果。     

尿清舒颗粒治疗慢性非细菌性前列腺炎(湿热下注证)的有效性与安全性

目的：探讨应用尿清舒颗粒治疗慢性非细菌性前列腺炎（湿热下注证）的有效性与安全性。方法：采用分层区组随机、双盲双模拟、阳性药平行对照、多中心的临床试验研究方法,应用尿清舒颗粒对444例慢性非细菌性前列腺炎患者进行为期4周的治疗,其中观察组333例,给予尿清舒颗粒与前列腺胶囊模拟剂,对照组111例,给予前列腺胶囊与尿清舒颗粒模拟剂。以西医症状积分（慢性前列腺炎NIH-CPSI症状评分）、中医症候疗效和单项症状积分、前列腺触诊、前列腺液常规检查为观察指标,并观察治疗前后患者的一般体格检查、血常规、尿常规、便常规、心电图和肝肾功能以及不良反应发生率,以评价其有效性与安全性。结果：治疗4周后,观察组患者在NIH-CPSI症状评分中,优于对照组,差异有显著性统计学意义（P<0.05）。西医症状单项积分评分中,排尿症状评分两组差异有显著性统计学意义（P<0.05）。2组患者在治疗前后中医症候总积分组间比较,观察组显著优于对照组,组间比较差异具有显著性统计学意义（P<0.05）,且2组在中医症候愈显率及总有效率进行组间比较,观察组与对照组差异具有显著性统计学意义（P<0.05）;中医单项症候比较,在"尿急、尿痛、舌质"三个单项症状上,观察组明显优于对照组,组间比较差异具有显著性统计学意义（P<0.05）,而其他单项症状比较,差异无统计学意义（P>0.05）。2组患者在前列腺触诊及前列腺液常规检查比较,差异无统计学意义（P>0.05）。两组试验前后血、尿、便常规及心、肝、肾功能检测均未发现明显异常。结论：尿清舒颗粒治疗非细菌性慢性前列腺炎（湿热下注证）疗效确切,临床服用安全,具有较好的临床应用前景,值得推广使用。     

An overview of dehydroepiandrosterone (EM-760) as a treatment option for genitourinary syndrome of menopause

ABSTRACT

Introduction: Dyspareunia caused by vulvovaginal atrophy is a primary symptom of genitourinary syndrome of menopause (GSM), a chronic, progressive medical condition that results from estrogen and androgen deficiency at menopause. Dehydroepiandrosterone (DHEA, prasterone) is an endogenous precursor steroid hormone that is metabolized into both androgens and estrogens that has been recently been approved by the FDA for the treatment of moderate to severe dyspareunia caused by vulvovaginal atrophy secondary to menopause.

Areas covered: This is a comprehensive drug evaluation describing the chemical composition, pharmacokinetics, metabolism, clinical efficacy and safety of dehydroepiandrosterone (prasterone) in the treatment of dyspareunia and VVA secondary to menopause. Preclinical and clinical data suggesting further potential uses, benefits, and contraindications in the genitourinary health of postmenopausal women are also considered.

Expert opinion: Intravaginal dehydroepiandrosterone (prasterone) is effective for the management of dyspareunia secondary to menopause and may be effective in the treatment of other types of sexual dysfunction that are secondary to menopause. Further studies should explore additional dosing regimens and different indications.     

Effects of plasticizers and surfactants on the film forming properties of hydroxypropyl methylcellulose for the coating of diclofenac sodium tablets

Hydroxy propyl methyl cellulose (HPMC) 5cPs, an aqueous soluble polymer was employed for coating diclofenac sodium (DFS) tablets 25 mg for protecting the integrity of the drug yet rendering the drug to release at a faster rate on contact with the gastric environment. Proper optimization for the aqueous based film coating formulation was undertaken primarily employing plasticizers like polyethylene glycol (PEG) 400 and propylene glycol (PG). The defect free selected formulations were further subjected for studying the effects of surfactants like sodium lauryl sulphate (SLS) and Tween-80 along with the plasticizers. The quality of the aqueous film coats or the plasticizer efficiency in case of PEG-400 is in the order 1.5 > 0.5 > 1.0% and for PG 1 > 4 > 3% which can be stated on the basis of less incidence of major coat defects like chipping, cracking, orange peel, roughness, blistering, blooming, picking. The quality of aqueous film coat or the surfactant efficiency in case of SLS + PEG-400 is in the order 0.3 < 0.5 < 0.1% and SLS + PG is in the order 0.5 < 0.1 < 0.3%. In case of Tween-80 + PEG-400 the order is 0.3 < 0.5 < 0.1% and Tween-80 + PG is in the order 0.3 < 0.1 < 0.5%. Elegant film formation can be stated from fewer incidences of coat defects. The obtained coated tablets eventually satisfied all the normal physical parameters like thickness, weights, and weight gain, drug content, crushing strength, percent friability, disintegration time, dissolution profile and possible drug–polymer interactions. ANOVA was undertaken followed by Dunnet multiple comparison for the dissolution profile considering uncoated as the standard. The difference was considered significant at p ⩽ 0.01.     

流延法制备口溶膜剂及其质量评价

设计并研制了用于实验室处方筛选及少量样品制备的实验室用涂膜机以及中试规模的药膜涂膜干燥机.分别用上述两种装备以流延法制备伏格列波糖口溶膜剂,并进行了膜剂小试到中试的工艺研究和质量评价.结果表明,小试及中试规模得到的膜剂在45 s内全部溶解,3 min内均基本释放完全,物理性能、含量及含量均匀度等指标均满足要求.