中药复方配伍的研究方法及其进展

中药复方是由2味或2味以上中药遵循中医理论组合而成的方剂。多味中药在合适的剂量配比之下,协同发挥作用,实现中医的整体调节治疗。研究中药复方的配伍对推动中药现代化发展、新药开发以及临床应用有着重要意义。近年来,研究者们在传统的"七情和合"与"君臣佐使"的基础上,运用新技术和新方法对中药复方的成分、药效活性和药代动力学性质等进行了研究,从不同角度探讨了中药复方配伍的科学内涵。同时,多种数理方法和模型的建立、网络药理学和数据挖掘方法的发展与应用,也对中药复方配伍研究提供了很大帮助。研究方法的发展虽促进了中药复方配伍的科学研究,但还需进一步建立适合中药复方配伍复杂关系的研究方法,以阐明中药复方及其成分/组分配伍的内在规律,进而构建新的现代中药复方,这也是目前中药复方配伍研究的重点任务。     

基于子宫内膜异位症与恶性肿瘤的相关性探析补肾化瘀法作用机制及中医理论依据

子宫内膜异位症其异位内膜组织虽然在形态学上呈良性表现，却具有类似恶性肿瘤的生物学特性。中医学一般认为，“正虚伏邪”为恶性肿瘤的病机特点；那么，肾虚血瘀既属于“正虚伏邪”的范畴，又体现了EMs发病学和疾病发生、发展过程中的主要特点。在“病证相应”的中医治则之下，补肾化瘀法的临床疗效主要表现为：缓解痛经症状、提高受孕率，以及调整月经周期。本文基于EMs与恶性肿瘤的相关性，通过分析补肾化瘀法治疗EMs的理论依据及其抑制异位内膜侵袭的调控机制，主要包括解除免疫抑制、阻断局部微血管新生等，旨在阐明其疗效显著的原因，为临床推广提供可靠的基础研究证据。     

Physiological pharmacokinetics and pharmacodynamics of (+/-)-verapamil in female rats

Tissue distribution and pharmacodynamics of verapamil were evaluated during steady state intravenous (i.v.) infusion and after single dose intraperitoneal (i.p.) drug administration to female Sprague-Dawley rats. In one group of rats, verapamil was infused to a steady state concentration at which time animals were killed. Verapamil-induced decreases in mean arterial pressure (MAP) were monitored during infusion and correlated with concomitantly obtained plasma verapamil concentrations. Tissue (lung, liver, renal medulla, renal cortex, cardiac muscle, skeletal muscle, perirenal fat, brain stem, cerebral cortex, and cerebellum) and plasma samples were obtained immediately after animals were killed and verapamil and norverapamil concentrations determined. Another group of rats, after receiving i.p. verapamil, were killed at 1, 3, 5, 19, and 24 h. Elimination from each tissue evaluated was described by a first order process. Elimination half-life of verapamil was similar among plasma and tissues evaluated (1.5 to 2.2 h). The per cent verapamil not bound to plasma proteins was concentration-independent and similar between rats receiving i.p. (mean +/- S.D.) (2.28 +/- 0.72 per cent) and i.v. (2.08 +/- 0.03 per cent) verapamil. MAP and verapamil concentration in plasma (r = 0.75; p less than 0.01) and cardiac muscle (r = -0.82; p less than 0.01) were inversely correlated in a highly significant fashion during both i.v. and i.p. drug administrations. The tissue-to-plasma distribution ratio for verapamil and norverapamil was similar among animals receiving i.p. verapamil at all points of sampling, suggesting distribution equilibrium had been achieved. After steady state i.v. infusion, both verapamil and norverapamil tissue: plasma concentration ratios were greater than after i.p. administration. Higher tissue: plasma verapamil concentration ratios after i.v. administration than after i.p. administration suggest either only a pseudoequilibrium is attained after i.p. administration or that determinants of tissue distribution of racemic verapamil differ with different routes of drug administration. In these studies, MAP provided a reasonable pharmacodynamic marker for verapamil tissue and plasma concentrations.     

复方18甲基炔诺酮透皮控释传递系统的LNG人体药物动力学与药效学评价

复方18甲基炔诺酮/雌二醇透皮控释传递系统(LNG/E_2 TCDS)能同时恒速释放低剂量的LNG和E_2,在1周内维持一个平稳而有效的LNG血药浓度。药动学与药效学研究证明,该系统释放的LNG能达到血清LNG目标水平,产生有效的排卵抑制(6/6)。LNG/E_2 TCDS可望发展成为一种安全、有效、非侵入性的新型生育调节避孕制剂。     

肾上腺素对丁哌卡因肌间沟臂丛神经阻滞的药效学与药代动力学的影响

目的:了解肾上腺素对丁哌卡因肌间沟臂丛神经阻滞的药效学及药动学影响。方法:选择ASA Ⅰ～Ⅱ级肩部或上肢择期手术患者16例,随机分成两组,试验组与对照组各8例,分别用含或不含肾上腺素的0.75％丁哌卡因2mg/kg行肌间沟臂丛阻滞。对比观察两组的临床效果及药代动力学。结果:与对照组比较,试验组阻滞完善时间及镇痛时间延长(P<0.05或0.01)。试验组与对照组Cmax分别为0.8295±0.2893ug/ml和0.8898±0.2572ug/ml,Tmax分别为37.6018±8.3461分钟和29.3156±11.1991分钟(P>0.05)。药代动力学参数t1/2Ka及K_(21)两组间有显著性差异(P<0.05或0.01)。结论:肾上腺素能延长丁哌卡因的阻滞完善时间、镇痛维持时间及吸收半衰期,但对血药浓度无明显影响。     

牙槽裂植骨改善唇腭裂患者鼻底塌陷畸形

分析唇腭裂患者牙槽裂植骨与改善鼻底塌陷畸形的关系。方法：对同一术者所行牙槽裂植骨术的单侧唇腭裂患者48例进行临床研究，结合X线片及面部正侧位照片探讨植骨成功与否与鼻底塌陷畸形改善的关系。结果：植骨成功组的患侧鼻底塌陷畸形的改善较未成功组有明显差异，明显高于未成功组。结论：牙槽裂植骨成功后患侧鼻底塌陷畸形可以得到明显改善。     

提高中医临床疗效的科学学检讨(连载三)

中医学的生命力在于临床疗效 ,社会对于中医学的需要也在于临床疗效。提高中医临床疗效的科学学研究 ,要以中医基础理论为依据 ,以理、法、方、药一脉相承的辨证论治为前提。造成中医临床疗效下降的问题在于“三个脱节” ,即中医学与自身文化基础脱节 ,中医临床与辨证论治脱节 ,中药与中医临床脱节。中医学正处于行将消亡的边缘 ,也处在新的突破的前夜。实事求是地进行科学、历史的反思 ,中医学完全有可能走出百年困惑 ,得到振兴和发展。     

青山抗癌注射液抑制小鼠肿瘤生长的实验研究

目的：研究青山抗癌注射液对动物移植性肿瘤生长的影响．方法：以小鼠移植性肉瘤S180和肝癌H22为模型，以顺铂(DDP)为阳性对照，生理盐水(阳)为阴性对照，观察青山抗癌注射液对肿瘤生长的影响。结果：青山抗癌注射液不同剂量组对小鼠移植性肉瘤S180和肝癌H22的生长均显示了明显的抑制作用，与NS对照组相比，P＜0.01，且呈现出量效关系．结论：青山抗癌注射液具有抑制肿瘤生长的作用.     

Effect of omeprazole on the anticoagulant activity and the pharmacokinetics of warfarin enantiomers in rats

The effect of the proton pump inhibitor omeprazole on the anticoagulation and the pharmacokinetics of warfarin enantiomers was studied in rats. Omeprazole given intraperitoneally in a daily dose of 0.67 mg/kg over 8 days had no significant effect on the absorption, distribution and the total serum clearance values of the S- and R-enantiomers of warfarin. Omeprazole did not affect the pre-treatment baseline blood coagulation and the in vitro rat serum protein binding of warfarin enantiomers. In vitro study with rat liver microsomes showed that omeprazole had an inhibitory effect on the hydroxylation of warfarin enantiomers. Results obtained from in vivo urinary excretion study revealed that omeprazole inhibited the formation clearance of both S- and R-form oxidative metabolites, but increased that of the overall reductive metabolites, and the renal clearance of S- and R-enantiomers, of warfarin. As a consequence, the total serum clearance values for warfarin enantiomers remained unchanged and the hypoprothrombinaemic response produced by warfarin was not affected.     

An open label trial of raclopride in acute schizophrenia. Confirmation of D2-dopamine receptor occupancy by PET

Raclopride, a highly selective D2-dopamine receptor antagonist, was administered in doses up to 4 mg b.i.d. to ten schizophrenic patients in an open label non-comparative study lasting 4 weeks. Safety, tolerability, potential antipsychotic effect, prolactin response and drug effect on plasma homovanillic acid were evaluated. Central D2-dopamine receptor occupancy was determined by positron emission tomography (PET). No major deviations were found in biochemical and physiological safety parameters. Raclopride was well tolerated. The mean BPRS score was reduced by 55% at endpoint. In the global evaluation seven patients were very much or much improved. Extrapyramidal side effects were recorded in four patients and disappeared after dose reduction or single doses of biperiden. An increase in plasma prolactin of short duration was observed in both sexes. A significant decrease of plasma HVA was obtained after 4 weeks of treatment. In two of the patients the central D2-dopamine receptors occupancy was measured using PET. The receptor occupancy was 68 and 72% which is the same as that found in patients treated with conventional neuroleptics.