国产硫酸氯吡格雷片降低血小板聚集率的临床观察

目的：比较国产氯吡格雷片（CPG）和噻氯吡啶片（TCP）降低血小板聚集率的疗效和安全性。方法：240例高血小板聚集率的患者随机分为CPG组（CPG50mg）和TCP组（TCP250mg）进行双盲、对照治疗4wk,观察治疗前后血小板聚集率的变化和不良反应。结果：CPG组和TCP组降低血小板聚集率的疗效相同[二磷酸腺苷（ADP）0.5μmol/L诱导,CPG组降低28.8％,TCP组降低32.8％,P＝0.23;ADP1.0μmol/L诱导,CPG组降低34.3％,TCP组降低37.2％,P＝0.42]。CPG组的不良反应较少。结论：国产CPG（50mg）与TCP（250mg）有等效的抗血小板聚集作用,而且安全性较好。     

盐酸苯环壬酯及其光学异构体的细胞毒性

目的研究新型抗胆碱能药物盐酸苯环壬酯(CPG)及其光学异构体S( )-CPG和R(-)-CPG的细胞毒性.方法人肝肿瘤细胞HepG、人近曲肾小管上皮细胞HK-2及人胚肺成纤维细胞HLF染毒不同浓度的CPG,S( ).CPG和R(-)-CPG,采用中性红吸收法测定半数抑制浓度(IC50).结果CPG,S( )-CPG和R(-)-CPG均以浓度依赖的方式降低细胞存活率,它们对HepG2细胞的IC50分别为192.5,193.6和217.0μmol·L-1,对HK-2细胞的IC50分别为181.8,196.0和208.8μmol·L-1,对HLF细胞的IC50分别为223.7,233.9和244.6μmol·L-1.结论CPG与其光学异构体S( )-CPG和R(-)-CPG的细胞毒性没有明显差异.     

羧肽酶G2在大鼠体内的组织分布及排泄

目的 探究[125I]标记的羧肽酶G2([125I]CPG2)尾静脉推注给予Wistar大鼠后的组织分布和排泄随时间的变化.方法 采用同位素示踪的方法,大鼠尾静脉推注[125I]CPG2700μg·kg-1后,于0,0.08,0.5,1,2,4,14和24 h经眼眶静脉采血,用酸沉放射性计算血药浓度,分析药物浓度-时间...     

用控制微孔玻璃珠制备高纯度因子Ⅷ

控制微孔玻璃珠(CPG)层析可用于大规模提纯因子Ⅷ。CPG由几乎是纯的SiO_2颗粒组成,其90%以上的体积为具有特定直径的分子通道(微孔),它的各种性质适用于层     

大剂量应用甲氨蝶呤后用羧肽酶G_2解救治疗

单用甲氨蝶呤(MTX)是最有效的、治疗原发性中枢神经系统淋巴瘤(PCNSL)的药物,部分因为大剂量应用MTX时,它能透过完好的血脑屏障(BBB)。而随后必须用亚叶酸解救MTX的毒性作用对全身器官的损害,特别是骨髓和胃肠道。但是亚叶酸也可能解救肿瘤细胞免除MTX的致死性作用。羧肽酶G2(CPG2)不仅能迅速裂解MTX为谷氨酸和2,4二氨基N10甲基蝶酸(DAMPA),而且不透过BBB,即使BBB的通透性异常时也不透过该细胞膜,因而不会抵消细胞内MTX的作用,所以CPG2有可能替代亚叶酸作为大剂量应用MTX后的解救药。作者对4名复发性PCNSL病人联用大…     

果胶作为蛋白质口服给药载体的研究

蛋白质药物大多经胃肠外给药,为减少长期注射引起的健康危害,迫切需要研究经胃肠道途径给药并发展具有控释作用的制剂。本研究的目的就是以牛血清蛋白(BSA)为模型蛋白,调查果胶以果胶酸钙凝胶(CPG)小球的形式,用于蛋白质口服给药系统的适用性。制备CPG小球利用低酯果胶的?..     

珠母贝氨基多糖的分离纯化及其抗肿瘤活性的初步研究

探讨珠母贝氨基多糖的分离纯化及其抗肿瘤活性。马氏珠母贝全脏器经胰酶和枯草杆菌蛋白酶双酶水解、醇沉后得到氨基多糖粗品(CPG)．再经DEAE-52-纤维素柱纯化，并采用MTT法检测其体外抗肿瘤活性。结果表明：CPG和经DEAE-52-纤维素柱纯化级分GAG-1，GAG-2中总氨基己糖的质量分数分别为45．9％，56．5％和59.2％，级分GAG-1硫酸基的质量分数高达13.8％；体外抗肿瘤试验表明CPG，GAG-1和GAG-2具有抑制肿瘤细胞生长的作用，对HL-60细胞的抑制率分别为54．6％。50.0％和35．4％，且能显著增敏化疗药物5-Fu抑制肿瘤细胞的作用，其中GAG-1为主要的活性成分。     

FDA的CPG对我国药品执法的借鉴

执法政策指南(Compliance Policy Guides)是FDA制定的用于解释该机构在执行有关法律、法规时的法律问题.CPG给FDA的地方执法提供了可以参照的标准及程序,对保证执法质量有着非常重要的意义.     

维持气管导管合适套囊压方法探讨

全麻气管插管时,导管气囊压力不当可致气管黏膜缺血损伤、术后声嘶、咽喉痛等并发症[1,2].常用的套囊充气法有:手指捏感法、最小容积阻塞法和套囊充气测压仪(Cuff Pressure Gauge,CPG)充气法.手指捏感法盲目性很大,最小容积阻塞法太繁锁,套囊充气测压仪(Cuff Pressure Gauge,CPG)充气法是一种科学、理想的方法,但不是每家医院或每个手术间都能配备套囊充气测压仪.因此,寻找一种简单实用的替代方法具有很好的临床意义.     

浅谈中成药合理应用的重要性

通过调查我院近3年来的中成药处方,对中成药的临床合理应用进行分析,为临床合理应用中成药提供参考。     

NMDA receptor antagonists change behavioral activity of rats treated with (S)-4CPG

The effect of (S)-4CPG [(S)-4-carboxyphenylglycine] (25, 50, 100 nmol icv) and the effect of AP-7 (5 nmol icv) or MK-801 (5 nmol icv) on the processes of acquisition, consolidation of conditioned reflexes and locomotor activity were tested in rats. Neither AP-7, MK-801 nor (S)-4CPG given alone changed locomotor activity. MK-801 significantly increased the effects of (S)-4CPG: on crossings at all applied doses, on rearings at 100 nmol, and on bar approaches at 50 nmol of (S)-4CPG. AP-7 enhanced the effects of 50 and 100 nmols of (S)-4CPG on crossings, 100 nmol of (S)-4CPG on rearings in the open field test. Neither AP-7, MK-801 nor (S)-4CPG at doses of 50 and 100 nmols influenced acquisition, but (S)-4CPG given alone at a dose of 25 nmol impaired acquisition. MK-801 impaired the action of 50 and 100 nmols of (S)-4CPG on acquisition. AP-7 only at a dose of 100 nmol inhibited (S)-4CPG-induced acquisition. Neither AP-7, MK-801 nor (S)-4CPG given alone changed consolidation in passive avoidance situation while co-administration of AP-7 and (S)-4CPG at the doses of 50 and 100 nmols, affected this process. The obtained results support our hypothesis concerning the co-operation between group I mGluRs and NMDA receptors in some behavioral tests and the modulating effect of group I mGluRs antagonist on central action of NMDA receptor antagonists.     

Covalent linkage of carboxypeptidase G2 to soluble dextrans--II. In vivo distribution and fate of conjugates

The in vivo fate of the therapeutic enzyme, carboxypeptidase G2 (CPG2) in native form and covalently-linked to soluble dextrans was studied in the mouse using radiolabelled compounds. Clearance, from the blood, of all compounds tested was found to be as intact, active material, whilst excreted radiolabel was associated in all cases with low molecular weight substances. The clearance and excretion rates of native CPG2 were found to balance, but this was not so for dextran-CPG2 conjugate or CNBr-activated dextran. Tissue distribution studies demonstrated that there was little or no tissue uptake of native CPG2, whereas dextran-CPG2 conjugate, and CNBr-activated dextran were retained in the liver. Within the liver, the CPG2 component of dextran-CPG2 conjugate was degraded more rapidly than the dextran moiety. Blockade of reticulo-endothelial system (RES) led to increased half-lives of dextran CPG2 conjugate and CNBr-activated dextran, demonstrating the involvement of the RES in the clearance of these compounds. Impairment of RES activity did not affect the clearance rate of native CPG2. These results are discussed in relation to the potential use of dextran-CPG2 conjugates in cancer chemotherapy.     

Calcium pectinate gel beads for controlled release drug delivery:: I. Preparation and in vitro release studies

Calcium pectinate gel (CPG) beads of indomethacin, a poorly soluble drug, were prepared by dispersing indomethacin in a solution of pectin and then dropping the dispersion into calcium chloride solution. The droplets instantaneously formed gelled spheres by ionotropic gelation. The effect of several factors such as pectin type, the presence of a hardening agent and the drug loading were investigated on the percentage of drug entrapped, size distribution and drug release from the CPG beads. The release characteristics were studied using the rotating basket dissolution method. Strong spherical beads with narrow size distributions, high yields and good entrapment efficiencies could be prepared. All factors investigated have significantly affected the release of indomethacin from CPG beads. The mechanism of drug release from CPG beads followed the diffusion controlled model for an inert porous matrix. Therefore, calcium pectinate gel could be a useful carrier for controlled release drug delivery of poorly soluble drugs.     

Self-immolative anthracycline prodrugs for suicide gene therapy.

Four novel potential prodrugs derived from daunorubicin (8, 10) and doxorubicin (12, 14) were designed and synthesized. They are self-immolative prodrugs for suicide gene therapy activation by the enzyme carboxypeptidase G2 (CPG2) subsequently releasing the corresponding anthracyclines, by a 1,6-elimination mechanism. A mammary carcinoma cell line (MDA MB 361) was engineered to express CPG2 intracellularly (CPG2) or extracellularly, tethered to the outer cell membrane (stCPG2(Q)3). The prodrugs derived from doxorubicin showed prodrug/drug cytotoxicity differentials of 21-fold (compound 12) and 23-fold (compound 14). Prodrug 12 underwent an 11-fold activation when assayed in the cell line expressing externally surface-tethered CPG2.     

克林霉素磷酸酯凝胶治疗痤疮

目的：观察克林霉素磷酸酯凝胶治疗痤疮的疗效。方法：痤疮１５４例随机分成３组,克林霉素磷酸酯凝胶１０４例,其中试验组５０例（男性１３例,女性 ３７例;年龄 ２３ ａ＋ ｓ ６ ａ）,开放组 ５４例（男性 １３例,女性 ４１例;年龄 ２４ ａ＋ ７ ａ）。磷酸克林霉素洗液５０例为对照组（男性 １８例,女性 ３２例;年龄２６ ａ±７ ａ）。上述药物每日早晚各 １次涂于患部,疗程均 ４ ｗｋ。结果： ３组治疗后炎性丘疹、脓疱改善较治疗前差异有显著意义（Ｐ＜０．０５或Ｐ＜０．０１）。试验组与对照组症状改善及疗效比较,差异无显著意义（Ｐ＞０．０５）。结论：克林霉素磷酸酯凝胶治疗痤疮疗效佳。     

Calcium pectinate gel beads for controlled release drug delivery:: I. Preparation and in vitro release studies

Calcium pectinate gel (CPG) beads of indomethacin, a poorly soluble drug, were prepared by dispersing indomethacin in a solution of pectin and then dropping the dispersion into calcium chloride solution. The droplets instantaneously formed gelled spheres by ionotropic gelation. The effect of several factors such as pectin type, the presence of a hardening agent and the drug loading were investigated on the percentage of drug entrapped, size distribution and drug release from the CPG beads. The release characteristics were studied using the rotating basket dissolution method. Strong spherical beads with narrow size distributions, high yields and good entrapment efficiencies could be prepared. All factors investigated have significantly affected the release of indomethacin from CPG beads. The mechanism of drug release from CPG beads followed the diffusion controlled model for an inert porous matrix. Therefore, calcium pectinate gel could be a useful carrier for controlled release drug delivery of poorly soluble drugs.     

Novel fluorinated prodrugs for activation by carboxypeptidase G2 showing good in vivo antitumor activity in gene-directed enzyme prodrug therapy

Sixteen novel polyfluorinated benzoic acid mustards have been synthesized for use in gene-directed enzyme prodrug therapy (GDEPT). Eight of these were benzoic acid L-glutamate mustards for evaluation as prodrugs and the other eight were the active drugs formed by the action of the bacterial enzyme carboxypeptidase G2 (CPG2). All of the di- and trifluorinated prodrugs were efficiently cleaved by the enzyme. In contrast, the tetrafluorinated prodrugs were found to be competitive inhibitors of CPG2, the first such inhibitors to have been described. The di- and trifluorinated prodrugs were differentially cytotoxic to human breast carcinoma cells (MDA MB 361) expressing CPG2, compared to control cells that did not express the enzyme. The difluorinated prodrug {4-[bis(2-bromoethyl)amino]-3,5-difluorobenzoyl}-L-glutamic acid and its iodoethylamino analogue were effective substrates for the enzyme and showed excellent therapeutic activity in CPG2-expressing MDA MB 361 xenografts, either curing or greatly inhibiting tumor growth and extending the life of the animals.     

Effect of calcium concentration, hardening agent and drying condition on release characteristics of oral proteins from calcium pectinate gel beads.

Pectin has been investigated for its ability to produce solid calcium pectinate gel (CPG) beads containing bovine serum albumin (BSA). Several factors can influence the properties and release characteristics of the CPG beads. In this study, the effect of calcium concentration, hardening agent and drying condition on the encapsulation and release characteristics of BSA from the matrix gel beads made of calcium pectinate were studied. BSA release studies under conditions mimicking mouth to colon transit have shown that calcium pectinate protects the drug from being released completely in the physiological environment of the upper gastrointestinal tract, and is susceptible to the enzymatic action with consequent drug release. In addition, the release of BSA from CPG beads was strongly affected by calcium concentration and drying condition. However, the release was not particularly affected by the presence of hardening agent at the concentration of 1% or lower. Since the release of BSA as a model protein drug could be controlled by the regulation of the preparation conditions of CPG beads, the CPG beads may be used for a potential oral controlled release system for protein drugs.     

The effect of acute ethanol administration on phosphorylcholine uptake and metabolism in rat liver slices

Liver slices obtained from normal and acutely ethanol-intoxicated rats were incubated with labelled choline plus unlabelled orthophosphate or labelled phosphorylcholine (PC). After variable times of incubation hydrosoluble compounds and choline phosphoglycerides (CPG) were extracted from the tissue and analyzed. When compared to controls, the slices obtained from intoxicated livers accumulated more PC and synthesized more CPG when incubated with PC; on the other hand, when incubated with choline, they accumulated less PC. From these results it can be concluded that PC is a better lipid precursor in intoxicated livers, than in normal ones. In any case CPG becomes better labelled after incubation with choline than with PC; base-exchange could be liable for this result.