辅酶A口服剂与泛硫乙胺对家兔食饵性高脂血症作用的比较

目的:比较辅酶A口服剂(辅酶A 辅酶A保护剂)与泛硫乙胺口服给药对家兔食饵性高脂血症的作用.方法:56只雄性新西兰白兔随机分为7组,每组8只.其中1组饲以普通饲料作为正常对照组,另外6组饲以高脂饮食20 d制备高脂血症模型,20 d后随机选择3组每日给予辅酶A保护剂[825 mg/(kg·d)] 高中低3个剂量的辅酶A [100、800、1 500 U/(kg·d)].其余3组分别给予辅酶A前体药--泛硫乙胺[1 200 mg/(kg·d)]、辅酶A保护剂[825 mg/(kg·d)]、辅酶A原药[800 U/(kg·d)],口服给药20 d.治疗前后测定动物血总胆固醇、三酰甘油、低密度脂蛋白胆固醇、高密度脂蛋白胆固醇水平.结果:给药20 d后,辅酶A口服剂高、中剂量组动物总胆固醇、低密度脂蛋白胆固醇显著降低,其效果与泛硫乙胺无显著差别.大剂量辅酶A可降低家兔三酰甘油水平,泛硫乙胺无此作用,辅酶A原药未见明显的降脂作用.结论:辅酶A口服剂治疗高脂血症效果可能优于泛硫乙胺.     

泛硫乙胺治疗高脂血症40例

40例高脂血症患者(男26例,女14例;年龄55±9yr)服用安慰剂12wk后服泛硫乙胺200mg tid,po,共12wk,前后对比,泛硫乙胺明显降低血胆固醇(7.1±1.0mmol/L降至5.5±1.0mmol/L)和甘油三酯(46±16mmol/L降至31±13mmol/L),增高高密度脂蛋白(0.92±0.11增到1.2±0.3mmol/L),3项指标经t检验均有显著差异(P<0.05),几乎无副作用。     

反相高效液相色谱法测定泛硫乙胺的含量

目的:采用反相高效液相色谱法测定泛硫乙胺的含量。方法:采用Diamonsil C18色谱柱(150mm×4．6mm,5μm),以甲醇-水(65:35)为流动相,流速为1．0 mL/min,检测波长为210 nm。结果:线性范围为39．85-1 594．00 μg/mL,r=0．999 7,最低检测限为2．28 ng,样品溶液在72 h内稳定,平均回收率为99．85％,RSD小于1．10％(n=9),日内和日间RSD分别为0．16％和0．17％。结论:该法简便,结果准确可靠。     

Combined pantethine and probucol therapy for Japanese patients with non-alcoholic steatohepatitis

Aims: To evaluate the efficacy and mechanism of combined pantethine and probucol therapy in Japanese patients with non-alcoholic steatohepatitis (NASH), liver function, serum cytokines, serum adiponectin and liver biopsy findings were investigated. Methods: Sixteen patients with NASH and hyperlipidemia were treated with pantethine (600 mg/day) and probucol (500 mg/day) for 48 weeks. Results: The mean pretreatment aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were 66 IU/L and 113 IU/L, respectively, which showed a significant decrease with treatment to 33 IU/L and 51 IU/L (P < 0.01 and P < 0.05), respectively. Total cholesterol was also significantlydecreased (P < 0.01). In addition, the mean serum TGF-beta level was significantly decreased, while the mean serum level of high molecular adiponectin was increased. In eight patients, liver biopsy was performed both before and after treatment. In four of these patients, inflammation was improved, and fibrosis was improved in two patients. No side-effects of this treatment were noted. Conclusion: Combined pantethine and probucol therapy was safe and effective for Japanese NASH patients, with its efficacy being mediated through adiponectin and TGF-beta.     

Preclinical and clinical studies with cysteamine and pantethine related to the central nervous system

Vécsei, László and Erik Widerlöv: Preclinical and Clinical Studies with Cysteamine and Pantethine Related to the Central Nervous System. Prog. Neuro-Psychopharmacol. & Biol. Psychiat. 1990, : 835–862.

1. 1. Cysteamine is formed by degradation of coenzyme A (CoA) and causes somatostatin (SS), prolactin and noradrenaline depletion in the brain and peripheral tissues.

2. 2. Cysteamine influences several behavioral processes, like active and passive avoidance behavior, open-field activity, kindled seizures, pain perception and SS-induced barrel rotation.

3. 3. Cysteamine has several established (cystinosis, radioprotection, acetaminophen poisoning) and theoretical (Huntington's disease, prolactinsecreting adenomas) indications in clinical practice.

4. 4. Pantethine is a naturally occurring compound which is metabolized to cysteamine.

5. 5. Pantethine depletes SS, prolactin and noradrenaline with lower efficacy compared to that of cysteamine.

6. 6. Pantethine is well tolerated by patients and has been suggested to treatment of atherosclerosis. The other possible clinical indications (alcoholism, Parkinson's disease, instead of cysteamine) are discussed.

泛硫乙胺颗粒质量标准研究

目的 建立泛硫乙胺颗粒的质量标准.方法 用高效液相色谱法测定泛硫乙胺颗粒中泛硫乙胺的含量,色谱柱为C18,流动相为曱醇-水(45:55),流速1.0 mL·min-1,检测波长为UV 210 nm.用薄层色谱法检查有关物质,以硅胶G为薄层吸附剂,水饱和的丁酮溶液为展开剂,碘蒸气为显色剂. 结果 泛硫乙胺在313～492 μg·mL-1(n=5)范围内线性关系良好(r=0.9998);日内精密度RSD为0.6%(n=6).薄层图谱斑点清晰,空白无干扰,检测限为0.6 μg .3批样品泛硫乙胺的含量为标示量的98.9%～99.5%,有关物质均小于2%.结论 方法准确、重现性好;可用于该品的质量控制.     

辅酶A和泛硫乙胺对高脂血症患者的疗效比较

目的研究口服辅酶A和泛硫乙胺治疗高脂血症患者的疗效比较。方法本研究为随机、双盲、平行对照的多中心Ⅲ期临床试验,223例三酰甘油(TG)2.3～6.5 mmol·L~(-1)的高脂血症患者,随机分为辅酶A组(n=114)和泛硫乙胺组(n=109),分别每日口服辅酶A 400 U和泛硫乙胺600 mg,治疗8周。分别于第0、4、8周采血,测定血常规、血脂参数、尿常规、肝功能、肾功能、肌酸激酶和血糖。主要终点疗效指标为治疗前后TG的变化率,总胆固醇(TC)、高密度脂蛋白胆固醇(HDL-C)和低密度脂蛋白胆固醇(LDL-C)的变化率。并考察辅酶A和泛硫乙胺的安全性。结果治疗4周后,辅酶A组和泛硫乙胺组TG分别下降26.0%和17.4%;治疗8周后,分别下降33.3%和16.5%,两组间差异非常显著(P<0.01)。治疗8周后辅酶A组TC下降率高于泛硫乙胺组,有显著差异(P<0.05),两组间LDL-C和HDL-C及不良反应发生率均无显著差异(P>0.05)。结论泛硫乙胺和辅酶A均能降低TG,辅酶A作用优于泛硫乙胺,安全性良好。