香连胃漂浮片的制备及体外释放研究

目的制备香连胃漂浮片并考察其体外释放性能。方法以羟丙基甲基纤维素K4M(hydroxypropyl methylcellulose K4M,HPMC-K4M)、十六醇、碳酸氢钠(NaHCO3)、乳糖、聚维酮K30(povidone K30,PVP-K30)、硬脂酸镁为辅料,采用粉末压片法制备香连胃漂浮片;以盐酸小檗碱的累积释放度为指标考察制剂的体外释药性能;采用正交试验对HPMC-K4M、十六醇、NaHCO3用量进行优选。通过数据拟合方程探讨制剂中盐酸小檗碱、木香烃内酯的释药机制。结果最优处方为香连复方提取物60.0 g、HPMC-K4M30.0 g、十六醇8.0 g、NaHCO38.0 g、乳糖8.0 g、PVP-K304.8 g、硬脂酸镁1.2 g(200片量)。指标成分盐酸小檗碱和木香烃内酯的体外释药特性均符合Riger Peppas模型,为扩散与骨架溶蚀协同作用。结论成功制得香连胃漂浮片,漂浮滞后时间短,持续漂浮时间长,且具有缓释特性。     

愈骨疗伤片的处方筛选及制备工艺研究

  目的：优化愈骨疗伤片的制备工艺,筛选最优制剂处方。  方法：在考察提取物粒径基础上,以片剂中川续断皂苷溶出量作为考察指标,采用正交试验对搅拌速度、制粒速度和聚维酮K30浆液浓度三者关系进一步考察。采用单因素进一步优选润滑剂和包衣工艺条件。  结果：最佳的愈骨疗伤片处方为提取物颗粒中加入10%乳糖、7.5%羧甲基淀粉钠和2.5%聚维酮K30,以及0.5%硬脂酸镁混合后压片；采用低浓度乙醇包衣液进行包衣。  结论：制得的愈骨疗伤片制剂工艺稳定,包衣后改善了片剂的吸潮性,增加了产品的稳定性,更便于保存和运输。     

双歧杆菌四联活菌片联合四联疗法对HP阳性胃溃疡患者血清TGF-β1、G17、PGI的影响

目的探讨双歧杆菌四联活菌片联合四联疗法对幽门螺旋杆菌(HP)阳性胃溃疡患者血清转化生长因子-β1(TGF-β1)、胃泌素17(G17)、胃蛋白酶原I(PGI)的影响。 方法选取HP阳性胃溃疡患者98例,随机均分为对照组和联合组。对照组采用四联疗法,联合组采用双歧杆菌四联活菌片联合四联疗法治疗。比较两组临床疗效、胃黏膜组织学评分、血清TGF-β1、PGI、G17、胃动素(MTL)、不良反应等情况。 结果联合组治疗总有效率高于对照组(P＜0.05)。与治疗前比较,治疗后两组胃黏膜组织学各项评分、TGF-β1、G17、PGI均降低,MTL升高,且联合组较对照组更为显著(P＜0.05)。联合组不良反应总发生率低于对照组(P＜0.05)。 结论双歧杆菌四联活菌片联合四联疗法治疗HP阳性胃溃疡患者疗效满意,可调节胃肠激素水平,安全性良好,具有临床应用价值。     

Synthesis and evaluation of the structural and physicochemical properties of carboxymethyl pregelatinized starch as a pharmaceutical excipient

A pregelatinized starch (PGS) was derivatized with sodium chloroacetate (SCA) in alcoholic medium under alkaline condition to produce carboxymethyl pregelatinized starch (CMPGS) with various degrees of substitution (DS). Influence of the molar ratio of SCA to the glucopyranose units (SCA/GU), reaction time, temperature and the amount of sodium hydroxide on the degree of substitution (DS) and the reaction efficiency (RE) was studied. An optimal concentration of 30% of NaOH, for a reaction time of 1 h at 50 °C and molar ratio (SCA/GU) equal to 1.0, yielded an optimal DS of 0.55 and a RE of 55%. SEM micrographs revealed that the carboxymethylation assigned the structural arrangement of CMPGS and caused the granular disintegration. Wide angle diffraction X-ray (XRD) showed that the crystallinity of starch was obviously varied after carboxymethylation. New bands in FTIR spectra at 1417 and 1603 cm⁻¹ indicated the presence of carboxymethyl groups. The solubility and viscosity of CMPGS increased with an increase in the degree of modification. In order to investigate the influence of DS on physical and drug release properties, CMPGS obtained with DS in the range of 0.12–0.55 was evaluated as tablet excipient for sustained drug release. Dissolution tests performed in phosphate buffer (pH 6.8), with Ibuprofen as drug model (25% loading) showed that CMPGS seems suitable to be used as sustained release excipient since the drug release was driven over a period up to 8 h. The in vitro release kinetics studies revealed that all formulations fit well with Korsmeyer-Peppas model and the mechanism of drug release is non-Fickian diffusion.     

Single and Dual Drug Release Patterns from Shellac Wax-Lutrol Matrix Tablets Fabricated with Fusion and Molding Techniques

The objective of this investigation was to prepare the shellac wax matrix tablets by fusion and molding technique incorporated with Lutrol in different ratios to modify the hydrophobicity of matrix tablet. The matrix tablets with single drug were loaded either with propranolol hydrochloride or hydrochlorothiazide as hydrophilic and hydrophobic model drugs, and a dual drug formula was also prepared. The single and dual drug release patterns were studied in a dissolution apparatus using distilled water as medium. Propranolol hydrochloride released from matrix was easier than hydrochlorothiazide. Drug release from shellac wax matrix could be enhanced by incorporation of Lutrol. However retardation of drug release from some matrix tablets was evident for the systems that could form dispersion in the dissolution medium. The gel network from high content of Lutrol was hexagonal which was a dense and more compact structure than the other structures found when low amounts of Lutrol were present in the formula. Therefore, the formulae with high content of Lutrol could prolong drug release more efficiently than those containing low content of Lutrol. Hence shellac wax matrix could modulate the drug release with the addition of Lutrol. Sustainable dual drug release was also obtained from these developed matrix tablets. Thus shellac wax-Lutrol component could be used as a potential matrix tablet prepared with fusion and molding technique with excellent controlled drug release.     

凉血散瘀方对肾虚血瘀型 IgA 肾病患者的疗效观察

〔摘 要〕 目的：分析凉血散瘀方加减辅助雷公藤多苷、醋酸泼尼松片治疗肾虚血瘀型 IgA 肾病患者的临床效果。 方法：选取三明市中西医结合医院 2019 年 6 月至 2020 年 6 月期间收治的 70 例肾虚血瘀型 IgA 肾病患者，依照治疗方案不同分为 观察组与对照组，各35例。对照组给予西药治疗；观察组在对照组基础上加用凉血散瘀方加减治疗。比较两组治疗效果。 结果：观察组患者治疗总有效率为 91.43 %，高于对照组的 71.43 %，差异具有统计学意义（P ＜ 0.05）。治疗前两组患者的尿红细 胞个数、血清肌酐（Scr）、血尿酸（SUA）、24 h 尿蛋白定量、Ⅳ 型胶原（C–Ⅳ）、基质金属蛋白酶组织抑制物 –1（TIMP–1） 及层粘连蛋白（LN）比较，差异无统计学意义（P ＞ 0.05）；治疗后两组患者的尿红细胞个数、Scr、SUA、24 h 尿蛋白 定量、C–Ⅳ、TIMP–1 及 LN 均低于治疗前，且观察组患者的尿红细胞个数、Scr、SUA、24 h 尿蛋白定量、C–Ⅳ、TIMP–1 及 LN 均低于对照组，差异具有统计学意义（P ＜ 0.05）。观察组患者不良反应发生率为 2.86 %，与对照组的 8.57 % 比较，差异无统计学意义（P ＞ 0.05）。 结论：凉血散瘀方联合雷公藤多苷、醋酸泼尼松片治疗肾虚血瘀型 IgA 肾病患者， 可进一步改善患者病情，调节血脂水平，改善肾脏纤维化，且安全性不受影响。     

Enhanced dissolution of sildenafil citrate as dry foam tablets

Dry foam formulation technology is alternative approach to enhance dissolution of the drug. Sildenafil citrate was suspended in sodium dodecyl sulfate solution and adding a mixture of maltodextrin and mannitol as diluent to form a paste. Sildenafil citrate paste was passed through a nozzle spray bottle to obtain smooth foam. The homogeneous foam was dried in a vacuum oven and sieved to obtain dry foam granules. The granules were mixed with croscarmellose sodium, magnesium stearate and compressed into tablet. All formulations were evaluated for their physicochemical properties and dissolution profiles. All the tested excipients were compatible with sildenafil citrate by both differential scanning calorimetry (DSC) and infrared (IR) analysis. There are no X-ray diffraction (XRD) peaks representing crystals of sildenafil citrate observed form dry foam formulations. The hardness of tablets was about 5?kg, friability test <1% with a disintegration time <5?min. The sildenafil citrate dry foam tablet had higher dissolution rate in 0.1 N HCl in comparison with commercial sildenafil citrate tablet, sildenafil citrate prepared by direct compression and wet granulation method. Sildenafil citrate dry foam tablet with the high-level composition of surfactant, water and diluent showed enhanced dissolution rate than that of the lower-level composition of these excipients. This formulation was stable under accelerated conditions for at least 6 months.     

冠心宁片联合西药治疗冠心病稳定型心绞痛临床研究

目的:观察冠心宁片联合西药治疗冠心病稳定型心绞痛的效果及对血脂水平和炎症反应的影响。方法:选取冠心病稳定型心绞痛患者150例,采用随机数表法分为观察组和对照组各75例。对照组给予西医常规治疗,观察组在对照组的基础上联合冠心宁片治疗,2组均以4周为1个疗程,连续治疗3个疗程。比较2组患者血清总胆固醇(TC)、三酰甘油(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、超敏C-反应蛋白(hs-CRP)、肿瘤坏死因子-α(TNF-α)、单核细胞趋化因子-1(MCP-1)、心绞痛症状评分、中医证候评分及临床疗效。结果:经过治疗,观察组血清TG、TC、LDL-C、hs-CRP、TNF-α、MCP-1水平低于对照组,HDL-C水平高于对照组,差异均有统计学意义(P<0.05)。心绞痛评分及中医证候评分低于对照组,差异有统计学意义(P<0.05)。观察组总有效率为88.00%,高于对照组的73.33%,差异有统计学意义(P<0.05)。结论:使用冠心宁片联合西药治疗冠心病稳定型心绞痛患者,能够显著调节患者血脂水平,抑制炎症反应,改善临床症状,值得推广。     

二甲双胍联合炔雌醇环丙孕酮片对多囊卵巢综合征患者性激素和胰岛素水平的影响

目的:研究二甲双胍联合炔雌醇环丙孕酮片对多囊卵巢综合征(Polycystic ovarian syndrome,PCOS)患者性激素和胰岛素水平的影响。方法:选取2018年3月至2019年10月于我院就诊的PCOS患者135例,按照随机数字表法分为两组,对照组患者67例予以炔雌醇环丙孕酮片(每天1片)口服,研究组68例在对照组的基础上增加二甲双胍(每天0.85 g)口服。治疗3个疗程后,观察两组患者临床疗效、性激素水平、胰岛素水平、自然受孕率、不良反应。结果:研究组患者治疗后的临床有效率、受孕率明显高于对照组(P<0.05)。治疗后研究组黄体生成素(Luteinizing hrmone,LH)、睾酮(Testosterone,T)、卵泡刺激素(Follicle-stimulating Hormone,FSH)、胰岛素抵抗指数(Homeostasis model assessment insulin resistance,HOMA-IR)、空腹胰岛素(Fasting serum insulin,FINS)、空腹血清葡萄糖(Fasting plasma glucose,FPG)均显著低于对照组(P<0.05),雌二醇(Estradiol,E2)显著高于对照组(P<0.05)。两组患者不良反应发生率无显著差异(P>0.05)。结论:二甲双胍联合炔雌醇环丙孕酮片应用于PCOS患者可通过纠正性激素紊乱、改善胰岛素抵抗来提高临床疗效及自然受孕率,可临床推广。