Lumiracoxib does not affect the ex vivo antiplatelet aggregation activity of low-dose aspirin in healthy subjects

This randomized, double-blind, placebo-controlled study evaluated the pharmacodynamic effects of concomitant low-dose aspirin and lumiracoxib in healthy subjects. Participants received lumiracoxib 400 mg once daily (n = 14) or placebo (n = 14) for 11 days, with concomitant low-dose aspirin (75 mg once daily) from days 5 to 11. Ex vivo pharmacodynamic assessments included assays of platelet aggregation and urinary thromboxane and prostacyclin metabolite profile. Arachidonic acid-stimulated platelet aggregation was reduced from 76.3% on day 4 to 4.8% on day 11 in the placebo group and from 75.8% on day 4 to 5.1% on day 11 in the lumiracoxib group. Collagen-induced platelet aggregation was reduced from 77.5% on day 4 to 52.8% on day 11 in the placebo group and from 79.5% on day 4 to 55.9% on day 11 in the lumiracoxib group. Urinary thromboxane and prostacyclin were unaffected by lumiracoxib. In conclusion, concomitant lumiracoxib did not interfere with the cyclooxygenase-1-mediated antiplatelet effects of low-dose aspirin.     

噻吩并吡啶类抗血小板聚集药物研究概况

心脑血管疾病严重威胁人类健康,抗血小板治疗已经被证明可以有效预防和改善心脑血管疾病.噻吩并吡啶类药物是以二磷酸腺苷受体为靶点的一类抗血小板药物,包括噻氯匹定、氯吡格雷和普拉格雷,是目前临床上应用最为广泛、有效的抗血小板聚集、抗血栓药物,极大地改善了全球心脑血管患者的健康状况.概括介绍噻吩并吡啶类药物的代谢与起效模式、作用机制、临床应用及药物相互作用等方面的研究进展.     

金雀异黄酮的抗血小板聚集作用及机制

目的观察金雀异黄酮对血小板聚集的影响,并初步探讨其作用机制。方法制备家兔富血小板血浆和贫血小板血浆,并通过加入不同浓度的金雀异黄酮,测定其对凝血酶和血小板活化因子(PAF)诱导的血小板聚集的抑制作用;并测定其对凝血酶的抑制率及PAF诱导聚集下的血栓素(TXB2)、6-酮-前列腺-F1α(6-Keto-PGF1α)的水平。结果金雀异黄酮能明显抑制由凝血酶和PAF诱导的血小板聚集,且金雀异黄酮与凝血酶有一定的亲和力,在PAF诱导的血小板聚集中,金雀异黄酮能明显降低TXB2水平,升高6-Keto-PGF1α水平。结论金雀异黄酮能够明显抑制由凝血酶和PAF诱导的血小板聚集,其作用与抑制凝血酶有一定关系外,可能与其通过调节PAF诱导聚集TXA2和PGI2的释放有关。     

通脉对治疗血瘀证的抗血小板聚集和体外血栓作用的研究

目的 研究通脉不同部位抗血小板聚集和抗体外血栓作用。方法 采用二磷酸腺苷(ADP)诱导家兔血小板聚集,测定通脉不同部位对血小板聚集的抑制率;采用体外血栓法、全血血块法,观察通脉不同部位的抗血栓作用。结果 通脉石油醚部位和正丁醇部位有显著的抑制血小板聚集和抗血栓作用,高剂量石油醚部位和正丁醇部位对血小板聚集抑制率及体外血栓溶解率均＞50% ,差异有统计学意义(P<0.01),高剂量正丁醇部位48 h全血凝块溶解率＞65%,差异有统计学意义(P<0.01)。结论 通脉石油醚部位和正丁醇部位具有较强的抗血小板聚集和抗血栓作用。     

Octreotide-modified and pH-triggering polymeric micelles loaded with doxorubicin for tumor targeting delivery

A multifunctional mixed micelle was assembled for drug targeting delivery by combining two newly synthesized amphiphilic polymers, which were octreotide-polyethylene glycol-monostearate (OPMS) and N-octyl-N-succinyl-O-carboxymethyl chitosan (OSCC), respectively. The mixed micelle was designed to be characterized with long circulation, somatostatin receptors (SSTR)-mediated endocytosis and pH sensitivity. A series of assembling proportions of OPMS and OSCC was tested to reveal the effect of compositions on the functions. The particle size, zeta potential, drug loading and critical micelle concentration were examined. The dialysis test indicated a pH-triggering release behavior of the doxorubicin-loaded mixed micelle (DLMM), and faster release in acidic media (pH 4.0-6.0) in response to the protonation of carboxyl group. In addition, the PEG segments could efficiently protect the mixed micelle from plasma protein adsorption in vitro, and the DLMM composed of 20% OPMS and 80% OSCC provided the longest residence time after intravenous injection in rats in vivo. Due to SSTR mediated endocytosis, the significantly higher uptake of DLMM was observed in the tumor cells (SMMC-7721), compared with that in the normal cells (CHO) without SSTR expression. All the results suggested that the mixed micelle with multifunctional characteristics could be used as an effective approach for tumor treatment.     

Hemoptysis under diclofenac and antiplatelet doses of aspirin

A previously healthy 60-year-old man receiving aspirin for primary prevention of cardiovascular disease presented with hemoptysis after 1 week of treatment for his back pain with diclofenac. He had not suffered from any bleeding episode in the past and his family history was negative for hemorrhagic disorders. He had been a heavy smoker until his thirties, but had stopped smoking since then. After extensive workup, other pulmonary and nonpulmonary causes of hemoptysis were ruled out. Thus, in this case, because of the temporal relationship between exposure to the drug and the onset of symptoms, diclofenac was considered as the most probable cause of hemoptysis either alone or as a result of its pharmacodynamic interaction with aspirin. The adverse reaction was considered probable according to the Naranjo scale. Diclofenac treatment was discontinued and occasional use of acetaminophen for the back pain was recommended. Regular use of antiplatelet doses of aspirin was also discontinued.     

Furoquinolines with antiplatelet aggregation activity from leaves of Melicope confusa

Using antiplatelet aggregation as a guide for fractionation, four furoquinoline-type alkaloids, confusameline (1), skimmianine (2), kokusaginine (3), and O-methylconfusameline (4), were isolated from the leaves of Melicope confusa. All compounds showed significant antiplatelet aggregation activity.     

氯吡格雷联合阿司匹林在抗血小板治疗脑梗死的疗效观察

目的观察氯吡格雷联合阿司匹林抗血小板治疗脑梗死的疗效。方法选取2017年1月～2018年1月我院收治的急性脑梗死患者作为研究对象,随机分为观察组和对照组,每组40例,两组患者均予改善微循环、营养神经、平衡水电解质等常规治疗,并进行降压、降血糖等治疗,在常规治疗基础上,对照组予硫酸氢氯吡格雷片75mg/d,观察组同时联合阿司匹林肠溶片0.1g/d口服,两组均连续治疗14d。治疗后对比两组的临床疗效及神经功能改善情况。结果观察组患者治疗后无一例恶化,总有效率达95.0%、对照组患者治疗后无变化10例、恶化2例,总有效率为70.0%,两组临床疗效对比差异有统计学意义(P 0.05)。观察组40例脑梗死患者治疗后的NIHSS评分与治疗前的NIHSS评分对比分析显著降低(P 0.05);对照组40例脑梗死患者治疗后的NIHSS评分与治疗前的NIHSS评分对比分析也显著降低(P 0.05);两组患者治疗后的NIHSS评分对比,差异有统计学意义(P 0.05)。结论氯吡格雷联合阿司匹林在抗血小板治疗脑梗死中发挥了重要作用,显著提高了临床疗效,改善了患者的神经功能。     

二氢哒嗪酮类化合物的合成及其抗血小板聚集活性研究

目的：合成新的哒嗪酮类化合物，并研究其抗血小板聚集活性。方法：在6-（4-氯乙酰氨基苯基）-4，5-二氢-3（2H）-哒嗪酮侧链引入不同取代的哌嗪，合成了一系列化合物，采用^1H-NMR、IR及元素分析等方法确证其结构。采用Born比浊法进行体外抗血小板聚集药理实验。结杲：合成的10个化合物都具有一定的抗血小板凝集的活性，其中化合物4的抗血小板聚集活性明显优于先导化合物MCI-154。结论：4-位取代哌嗪环基的引入对哒嗪酮类化合物抗血小板聚集的活性有显著影响。     

Coordination of copper with aspirin enhances its anti-platelet aggregation activity

Anti-platelet aggregation of copper aspirinate, a copper complex of aspirin, has been studied in vitro and in vivo. The result shows that copper aspirinate is much more effective than aspirin against AA-, ADP- and PAF-induced platelet aggregation. Its mechanism is related to the inhibition of platelet cyclooxygenase and release of active substances from platelets, and to the promotion of PGI₂ level in plasma.     

Chemico-physical investigation of tenofovir loaded polymeric nanoparticles

Tenofovir (PMPA), an acyclic nucleoside phosphonate analog, is one of the most important drugs used for the HIV treatment. Unfortunately, several adverse reactions are related to its i.v. administration owing to the saturation of an anionic renal transporter. In order to improve the drug administration, the PMPA was embedded into a new type of nanocarriers based on poly-(d,l-lactide-co-glycolide) (PLGA) and/or chitosan (CH). The strategies for the preparation of nanoparticles (Nps) with a more efficient drug loading respect to the one reported in the literature for PMPA nanoencapsulation were investigated. CH was added in the first inner emulsion or in the external phase during the second emulsion of water/oil/water (W/O/W) Nps. The addition of CH in the first inner emulsion was the most promising technique. The Nps have a Z-average of 230nm, a Z-potential of -3mV and an EE% of 15 that was 2.5-3 times higher than that obtained with PLGA Nps or CH Nps. In vitro release studies showed a limited control on drug release in phosphate buffer (pH 7.4) while an initial burst effect followed by a slow drug release was observed in acidic receiving phase (pH 4.6). These results suggest the PLGA/CH Nps should be an effective and attractive anti-HIV drug carrier to study the cellular uptake and drug delivery on target cells such as macrophages.     

Dose-dependent aspirin hydrolysis and platelet aggregation in patients with atherosclerosis.

In a double blind, randomized trial, the effects of aspirin (1, 5, and 15 mg/kg) were compared with the changes in platelet aggregation at 6 and 24 hours after dosage. It is found that there is a negative correlation between aspirin hydrolysis velocity in blood and capability of aspirin to decrease platelet aggregation with ADP and collagen in patients with atherosclerosis. Relationship between these parameters depends on aspirin dosage. The correlation was more marked for low doses of aspirin. It is suggested that the effect of aspirin in low dosage on platelet aggregation might be ineffective in many patients without control of aspirin hydrolysis velocity in blood.     

新型磺酰胺类化合物SZ427的抗血小板聚集作用

目的研究新型磺酰胺类化合物4-乙氧基-N,N'-二(4-吡啶乙基)-1,3-苯二磺酰胺(SZ427)的抗血小板聚集作用。方法在体外药效学实验中,采用血小板聚集分析仪观察化合物SZ427对花生四烯酸(arachidonic acid,AA)、二磷酸腺苷(adenonisine disphosphate,ADP)和胶原诱导的家兔血小板聚集的影响。在体内药效学实验中,通过小鼠尾静脉出血时间、大鼠颈总动脉血栓和小鼠急性肺血栓三种模型分别观察化合物SZ427对出血时间、血栓质量和死亡时间的影响。结果在体外药效实验中,化合物SZ427能显著抑制AA、ADP和胶原诱导的家兔血小板的聚集作用;在体内药效学实验中,化合物SZ427能延长小鼠尾静脉出血时间,具有抗血小板聚集作用;能减少大鼠颈总动脉血栓质量,抑制血栓形成;能显著延长急性肺血栓小鼠的死亡时间,明显降低死亡率。结论化合物SZ427能抑制慢性血栓和急性血栓的形成,具有抗血小板聚集的作用。     

Formulation and evaluation of novel aspirin nanoparticles loaded suppositories

The main objective of the present work is to design aspirin nanoparticles loaded suppositories which will reduce the side effects caused by aspirin suppositories. Aspirin nanoparticles were prepared initially based on ionic-gelation mechanism and lyophilized. The prepared nanoparticles were evaluated, and the results confirmed that Fa9 formulation was the best with greater drug entrapment efficiency. Aspirin suppositories were prepared in order to investigate the best base composition. The prepared suppositories were evaluated and FS1, FS3, FS4, FS8, FS11, and FS12 were proved to be the best base compositions based on dissolution performed. The lyophilized aspirin nanoparticles of Fa9 were used to prepare aspirin nanoparticles loaded suppositories. The in vitro results revealed that Fas11 was the best formulation.     

Polyether-polyester diblock copolymers for the preparation of paclitaxel loaded polymeric micelle formulations

A number of hypersensitivity reactions have been attributed to the presence of Cremophor((R)) EL in the current formulation for paclitaxel. This has led to the development of formulations for paclitaxel employing polyether-polyester diblock copolymers as micelle forming carriers. Diblock copolymers of methoxypolyethylene glycol-block-poly(D,L-lactide) (MePEG:PDLLA) were synthesized from monomers of D,L-lactide and MePEG by a ring opening bulk polymerization in the presence of stannous octoate. Up to 25% paclitaxel could be loaded into matrices of MePEG:PDLLA (60:40, MePEG molecular weight of 2000) using the solution casting method. Dissolution of paclitaxel/copolymer matrices in aqueous media resulted in complete solubilization of paclitaxel within the hydrophobic PDLLA core of the micelles. This review article describes the synthetic reaction conditions influencing the degree of conversion of monomer to copolymer, thermal properties, critical micelle concentrations of copolymers, methods of incorporation of paclitaxel into copolymer matrices and subsequent constitution in aqueous media and biological evaluations of micellar paclitaxel.     

Resveratrol inhibits aggregation of platelets from high-risk cardiac patients with aspirin resistance

Up to 20% of serious vascular events in high-risk vascular patients is attributable to a failure of aspirin (ASA) to suppress platelet aggregation. Resveratrol is a cardioprotective phytoestrogen that can inhibit platelet aggregation in animal models. We hypothesized that resveratrol can also inhibit aggregation of platelets from ASA-resistant (ASA-R) patients. Thus, platelet-rich plasma was isolated from ASA-sensitive (ASA-S) and ASA-R patients (aspirin resistance was defined as higher-than-expected aggregation to collagen and epinephrine [>/=40%] after oral treatment with 100 mg/d ASA). Aggregation to adenosine diphosphate (ADP; 5 and 10 mumol/L), collagen (2 mug/mL), and epinephrine (10 mumol/L) in the absence and presence of resveratrol (10 mol/L) was measured by optical aggregometry. Maximal aggregation to 5 mumol/L ADP was only slightly affected by resveratrol. Similar results were obtained using 10 mumol/L ADP. Maximal aggregation of ASA-R platelets to collagen was significantly decreased by resveratrol, whereas resveratrol had only marginal effects in ASA-S platelets. Similar results were obtained with epinephrine as well. Collectively, resveratrol effectively inhibited collagen- and epinephrine-induced aggregation of platelets from ASA-R patients, which may contribute to its cardioprotective effects in high-risk cardiac patients.     

苯并咪唑-哒嗪酮类化合物的设计与合成及其抗血小板聚集活性

以具有抗血小板聚集活性的苯并咪唑类化合物和哒嗪酮类化合物为先导化合物 ,运用药物化学的拼合原理 ,设计并合成了 6个新的苯并咪唑 哒嗪酮类化合物及 6个新的苯并咪唑 苯并哒嗪酮类化合物 ,并经NMR和MS进行了结构鉴定 ,对其进行了抗血小板聚集的药理活性筛选。结果表明所合成目标化合物基本无抗血小板聚集活性     

聚合胶束载药多柔比星的研究进展

多柔比星（阿霉素，adriamycin）是临床上广泛使用的抗癌药，但其对正常组织的毒性和固有的多药耐药性是急需解决的问题。聚合胶束作为抗癌药的载体具有靶向作用，可减少毒副作用，提高抗癌药物的化疗指数。现对国外聚合胶束载药阿霉素的制备、理化性质、体外释放、生物学分布、抗肿瘤活性及靶向性进行综述。     

Celecoxib does not affect the antiplatelet activity of aspirin in healthy volunteers

Celecoxib is a novel cyclooxygenase-2-specific inhibitor for the management of acute pain, primary dysmenorrhea, and the signs and symptoms of arthritis. This double-blind, placebo-controlled study in 16 healthy volunteers evaluated whether celecoxib alters the effect of concomitant aspirin on platelet function. Volunteers received celecoxib (400 mg/day) or placebo for 4 days. On day 5, they also received a single 325 mg dose of aspirin with either 200 mg celecoxib or placebo. Thromboxane and platelet aggregation response to adenosine 5'-diphosphate (ADP), collagen, and arachidonic acid were measured before the first dose of celecoxib or placebo (baseline) and before dosing and 2 and 8 hours post dose on day 5. There was no significant difference in thromboxane inhibition between the two groups (percent inhibition: placebo 99.4%, celecoxib 99.0%; p = 0.555). There was also no significant difference in the effect of aspirin on platelet aggregation due to ADP, collagen, or arachidonic acid between the groups. Therefore, these data indicate that celecoxib does not alter the effects of aspirin on platelet function.