施保利通治疗带状疱疹临床疗效观察

目的:观察施保利通治疗带状疱疹的临床疗效.方法:将100例带状疱疹患者依数字随机法分为两组.治疗组50例采用施保利通,对照组50例,采用阿昔洛韦.结果:治疗组在水疱开始结痂、消退及疼痛缓解时间上明显优于对照组(P＜0.01).结论:施保利通治疗带状疱疹具有明显疗效.     

Chitosan‐tripolyphosphate nanoparticles as a possible skin drug delivery system for aciclovir with enhanced stability

Objectives The aim of the present study was to create a skin delivery system based on chitosan‐tripolyphosphate nanoparticles for aciclovir with enhanced chemical stability. Methods Nanoparticles were formed spontaneously using ionotropic gelation with tripolyphosphate. Two different sizes of aciclovir‐loaded nanoparticles were characterised in terms of zeta potential, particle size and polydispersity index. Key findings Standard diffusion experiments using Franz‐type diffusion cells showed reasonable skin permeability that depended on particle size and chitosan content. The larger the nanoparticle, having a higher chitosan content, the better the aciclovir permeation through porcine skin. Differential scanning calorimetry studies showed a remarkable decrease in the typical transition temperature, indicating an interaction between skin lipid bilayer and the nanoparticles. Moreover, the chemical stability of aciclovir was significantly increased by the nanoparticle system. After the observation period of 5 weeks, aciclovir incorporated into nanoparticles had undergone photo‐oxidation to a significantly lower extent than pure aqueous solution. This degradation product of aciclovir was analysed using LC/MS, and its identity established. Conclusions These studies demonstrate that incorporation of aciclovir into chitosan‐tripolyphosphate nanoparticles significantly improves its chemical stability. Moreover, skin diffusion studies in vitro showed improved permeation of aciclovir from the nanoparticle system, especially from nanoparticles with higher chitosan content.     

Topical Iontophoresis of Valaciclovir Hydrochloride Improves Cutaneous Aciclovir Delivery

Purpose To investigate the topical iontophoresis of valaciclovir (VCV) as a means to improve cutaneous aciclovir (ACV) delivery.Methods ACV and VCV electrotransport experiments were conducted using excised porcine skin in vitro.Results While the charged nature of the prodrug, VCV, enabled it to be more efficiently iontophoresed into the skin than the parent molecule, ACV, only the latter was detectable in the receptor chamber, suggesting that VCV was enzymatically cleaved into the active metabolite during skin transit. Iontophoresis of VCV was significantly more efficient than that of ACV; the cumulative permeation of ACV after 1, 2 and 3 h of VCV iontophoresis at 0.5 mA cm⁻² and using an aqueous 2 mM (∼0.06%) formulation was 20 ± 10, 104 ± 47 and 194 ± 82 μg cm⁻², respectively (cf. non-quantifiable levels, 0.1 and 1.0 ± 0.7 μg cm⁻² after ACV iontophoresis).Conclusions These delivery rates provide ample room to reduce either current density or the duration of current application. Preliminary in vitro data serve to emphasize the potential of VCV iontophoresis to improve the topical therapy of cutaneous herpes simplex infections and merit further investigation to demonstrate clinical efficacy.     

高效液相色谱荧光法测定人血浆中盐酸伐昔洛韦的代谢产物阿昔洛韦

目的:建立高效液相色谱荧光分析方法测定人血浆中盐酸伐昔洛韦的代谢产物阿昔洛韦(ACV)。方法:20例受试者单次、交叉口服盐酸伐昔洛韦片300mg后,以喷昔洛韦为内标,用沉淀法去除蛋白,用HPLC-荧光法测定。结果:ACV在0．02～5μg·mL~(-1)的浓度范围内有良好的线性关系(r=0．999 95),最低检测浓度为0．02μg·mL~(-1)(S/N＞3),ACV的相对回收率为96．08%～97．28%,绝对回收率为69．62%～72．02%(n=5),日内精密度RSD为3．33%～6．12%,日间精密度为2．37%～6．81%。结论:本方法简便、灵敏、特异性强,可用于血浆中ACV的测定及人体药动学研究。     

缬昔洛韦的合成

目的;对缬昔洛韦的合成进行了研究。方法：以阿昔洛韦和Ｎ－苄氧羰基－Ｌ－缬氨酸为原料,经酰化,催化氢解反应得到了新型抗疱疹毒药物缬昔洛韦。结果;本品的元素分析,红外,质谱及核磁共振图谱数据与文献报道一致,总收率为４５．２％,结论;采用此法合成缬昔洛韦是可行的,适合于工业生产。     

阿昔洛韦眼用凝胶基质对兔疱疹性角膜炎药效的影响

目的：通过药效试验论证卡波姆凝胶用作阿昔洛韦眼膏基质的可行性。方法：选用市售阿昔洛韦眼膏作为对照组，阿昔洛韦眼用凝胶剂为实验组，比较两者治疗实验性家兔单纯疱疹性角膜炎的药效差异。结果：实践组与对照组皆在平均治疗9d后角膜病变减轻；两组有效时间差异无显著性(P＞0．05)。结论：卡波姆凝胶对阿昔洛韦治疗实验性家兔单纯疱疹性角膜炎的药效与油性基质相同，无干扰作用，不影响主药发挥疗效，可用作该眼膏的基质。     

阿昔洛韦片中杂质的色谱-质谱结构分析

目的 建立高效液相色谱-四级杆-静电场轨道阱高分辨质谱(HPLC-Q-Exactive Orbitrap-MS)联用法对阿昔洛韦片及其强制降解试验样品中的杂质进行结构分析。方法 采用Waters Xbridge BEH Shield RP18(4.6 mm×250 mm,5μm)色谱柱,以10 mmol·L^–1甲酸铵溶液(含0.15%甲酸)为流动相A,以10 mmol·L^–1甲酸铵溶液(含0.15%甲酸)-乙腈(50∶50)为流动相B,进行梯度洗脱,检测波长为254 nm,对阿昔洛韦片及其强制降解试验样品中的杂质进行分离,再采用QExactive Orbitrap-MS测定各杂质一级精确分子量及二级碎片离子,并进行结构鉴定。结果 阿昔洛韦及其杂质均分离良好,检测并鉴定出阿昔洛韦片及其强制降解试验样品中8个含量>0.1%的主要杂质,其中4个为欧洲药典10.0规定的已知杂质,而其他杂质均未见报道。结论 建立的液质联用技术能有效鉴定阿昔洛韦片的杂质,能够为其生产工艺的优化和质量控制提供参考。     

Aciclovir‐resistant herpes keratitis

Herpes simplex virus (HSV) keratitis is a common cause of ocular morbidity. Resistance to aciclovir is probably under recognized. We describe three cases of aciclovir‐resistant herpes simplex virus keratitis treated with systemic foscarnet and present a review of the pharmacological options available to manage this condition.     

阿昔洛韦片在健康人体内的药代动力学及相对生物利用度

目的 测定阿昔洛韦片在健康人体内的药代动力学参数及相对生物利用度.方法 18名健康男性志愿者单剂量随机交叉口服500 mg阿昔洛韦片后,用高效液相色谱法测定血浆药物浓度.结果 口服海南金晓制药有限公司或天津药业集团新郑股份有限公司生产的阿昔洛韦片后的药代动力学参数分别为:T12(4.53±0.59)h和(4.65±0.55)h,Cmax分别为(451.08±77.19)μg·L-1(454.88±72.62)μg·L-1,Tmax分别为(1.67±0.24)h和(1.72±0.31)h,AUG01(2 312.1±372.2)μg·h·L-1和(2 249.8±258.9)μg·h·L-1.AuCo→∞.分别为(2 516.6±393.0)μg·h·L"和(2 446.1±272.5)μg·h.·L-1.两种阿昔洛韦片主要药动学参数间均无统计学意义(P＞0.05),受试阿昔洛韦片的相对生物利用度F为103.01%.结论 两种制剂具有生物等效性.可确保临床用药的安全有效.