Promoting absorption of drugs in humans using medium-chain fatty acid-based solid dosage forms: GIPET™

One of the most important and challenging goals in drug delivery is overcoming the poor oral absorption of high-value therapeutics that include peptides. Gastrointestinal Permeation Enhancement Technology (GIPET?) attempts to address this question by safely delivering drugs across the small intestine in therapeutically relevant concentrations. GIPET is based primarily on promoting drug absorption through the use of medium-chain fatty acids, medium-chain fatty acid derivatives and microemulsion systems based on medium-chain fatty acid glycerides formulated in enteric-coated tablets or capsules. Importantly, these excipients are generally regarded as safe and the systems are formulated in such a way that there is no change in chemical composition of the active ingredient. More than 300 volunteers have been administered GIPET formulations in 16 Phase I studies of 6 separate drugs comprising both single- and repeat-dosing regimes. Oral bioavailability of alendronate, desmopressin and low-molecular-weight heparin in humans was increased using GIPET formulations compared with unformulated controls. GIPET was well tolerated by human subjects. Using fluxes of markers of epithelial permeability, the effects of GIPET on the human intestine were shown to be rapid, short-lived and reversible in vivo. These data suggest that GIPET formulations have genuine potential as a platform technology for safe and effective oral drug delivery of a wide range of poorly permeable drugs.     

Impaired Anticoagulant Effect of Heparin in the Artificial Kidney: An Experimental Study

Bjo?rnson, J. &; Godal, H. C. Impaired Anticoagulant Effect of Heparin in the Artificial Kidney. An Experimental Study. Scand. J. clin. Lab. Invest. 36, 581–589, 1976.

Dialysis of blood and plasma was performed in vitro, in a ‘mini-Kiil’ dialyser as well as in dialysis bags. A marked shortening of the thrombin-clotting time was observed, indicating fall in heparin anticoagulant effect. The concentration of heparin, however, as measured by polybrene titration, was substantially less reduced. Fibrin formation, as evidenced by the ethanol gelation test, occurred more often in the dialysed than in the control plasma. In conclusion, the discrepancy between concentration and anticoagulant effect of heparin could be partly explained by influx from the dialysate of calcium, magnesium, and acetate ions. The fibrin-polymerizing effect of these ions was confirmed by a shortening of the clotting time with Reptilase, a proteolytic enzyme not influenced by thrombin inhibitors such as heparin. In addition, liberation of platelet factor 4 may be responsible for some reduction in antithrombin activity of heparin. No evidence of heparin being dialysed or adhering to the dialysis membrane was found.     

A Comparative Study of Paediatric Thermal Burns Treated with Topical Heparin and Without Heparin

Following reports of heparin use in burn treatment, an ethics-committee-approved prospective randomized study with controls compared results obtained using traditional usual burn treatment without heparin with results in similar patients similarly treated with heparin added topically. The subjects were 100 consecutive burn patients (age <15 years) with second-degree superficial and deep burns of 5–45 % total body surface area size. Two largely similar cohort groups—a control group (C) and a heparin group (H) with 50 subjects per group—were randomly treated. The 50 control group patients received traditional routine treatment, including topical antimicrobial cream, debridement, and, when needed, skin grafts in the early postburn period. The 50 heparin group patients, without topical cream, were additionally treated, starting on day 1 postburn, with 200 IU/ml sodium aqueous heparin solution USP (heparin) dripped on the burn surfaces and inserted into the blisters two to four times a day for 1–2 days, and then only on burn surfaces for a total of 5–7 days, before skin grafting, when needed. Thereafter, control and heparin group treatment was similar. It was found that the heparin patients complained of less pain and received less pain medicine than the control patients. The heparin group needed fewer dressings and oral antibiotics than the control group. The 50 heparin group patients had 4 skin graftings (8 %), while the 50 control group patients had 10 (20 %). Five control group patients died (mortality 10 %). No heparin group patients died. The number of days in hospital for the heparin group versus control group was significantly less (overall P < 0.0001): 58 % of heparin group patients were discharged within 10 days versus 6 % of control group patients; 82 % of heparin group patients were out in 20 days versus 14 % of control group patients; 98 % of the heparin group versus 44 % of the control group were out in 30 days; and while 100 % of heparin group patients were discharged by day 40, 56 % of the control group required up to another 10 days. Burns in heparin group patients healed on average in 15 days (maximum period 37 days) versus an average of 25 days (maximum >48 days) in control group patients (P < 0.0006). Procedures and costs in the heparin group were much reduced compared with the control group. Differences between the heparin and control groups are presented for the sake of comparison. It was concluded that heparin applied topically for 5–7 days improved burn treatment: it reduced pain, pain medicine, dressings, and use of antibiotics; it significantly reduced IV fluids (P < 0.04), days in hospital (P < 0.0001), and healing time (P < 0.0006); and it reduced skin grafts, mortality, and costs.     

低相对分子质量肝素联合护理干预预防肿瘤患者PICC置管后深静脉血栓形成

目的对经外周静脉置入中心静脉导管(PICC)术后深静脉血栓(DVT)发生规律进行相关探讨,同时探究低相对分子质量肝素(LMWH)对肿瘤患者PICC置管后深静脉血栓的预防效果。方法选择2014年3月至2016年10月期间600例PICC置管术后患者DVT的发生情况进行统计分析,并统计观察期间PICC置管术后发生DVT的患者使用LMWH并进行护理干预后深静脉血栓复发情况,将同期PICC置管术后未应用LMWH的患者设为对照组,并进行比较。结果 PICC置管术后DVT发生率为7.00%,其与伴糖尿病或高血压、冠心病、感染、长期卧床、D二聚体增高有明显的关系;应用LMWH后,PICC置管术后发生DVT的患者深静脉血栓发生率为0.00%,PICC置管术后未应用过LMWH的患者DVT发生率为7.00%,差异显著(P0.05)。结论肿瘤患者PICC置管后发生DVT概率较高,其与伴糖尿病或高血压、冠心病、感染、长期卧床、D二聚体增高有明显的关系;通过LMWH的使用以及积极的护理干预能对DVT的发生率进行显著的减少,同时具有很高的安全性。     

Administration of low-molecular-weight heparin in patients with two or more unsuccessful IVF/ICSI cycles: a multicenter cohort study

To compare the effects of the administration of low-molecular-weight heparin (LMWH) in subfertile patients with two or more unsuccessful IVF/ICSI cycles. In this six-center two-arm retrospective cohort study, the study population (230 women) underwent a GnRH-antagonist protocol and was classified into two groups, according to the couse of LMWH or not. Groups were compared regarding the clinical and IVF/ICSI cycle characteristics and reproductive outcomes, whereas clinical pregnancy and miscarriage constituted the primary endpoints. Logistic regression analysis was performed to determine the potential predictors of clinical pregnancy, miscarriage and live birth rates using the Enter method. Baseline characteristics were comparable in the two groups. There was no statistically significant difference between the two study groups with regard neither to clinical pregnancy and miscarriage rates (33/133 vs. 20/97, p?=?.456 and 15/133 vs. 9/97, p?=?.624, respectively), nor to the secondary outcomes preset for this study (all p values?>.05). Logistic regression revealed that age of the woman and ICSI and dose of gonadotrophins used were predictors of clinical pregnancy and live birth, respectively. In conclusion, there is no evidence to support the standard addition of LMWH in patients with two or more unsuccessful IVF/ICSI cycles.     

Heparin-Induced Thrombocytopenia and Vascular Surgery

Heparin-induced thrombocytopenia (HIT) is of special interest to vascular surgeons as heparin is the predominant anticoagulant used before, during, and after vascular surgery. Further, the prothrombotic nature of this antibody-mediated disorder leads to a high frequency of limb ischemia due to large arterial occlusion by platelet-rich (“white”) clots or because of extensive venous thrombosis involving large veins and small venules. This latter syndrome has been associated with coumarin anticoagulation of HIT-associated deep-vein thrombosis (coumarin-induced venous limb gangrene). Non-heparin anticoagulants, such as the direct thrombin inhibitors (lepirudin, argatroban), may be needed for intraoperative management of a patient with suspected acute HIT who requires vascular surgery. The transience of HIT antibodies provides a rationale for intraoperative use of heparin in a patient who has recovered from HIT and in whom HIT antibodies are no longer detectable.     

低分子肝素联合尿激酶治疗急性心肌梗死的临床研究

目的探讨低分子肝素与尿激酶在急性心肌梗死患者中的联合应用价值。方法选择急性心肌梗死患者104例，随机将患者分为研究组和对照组。对照组患者给予常规治疗，研究组患者加用低分子量肝素钠注射液与注射用尿激酶的药物联合治疗方案，比较两组患者的临床治疗情况。结果研究组患者的显著进步率和总有效率较对照组患者均明显提高，分别达到63.46％和92.31％，而无效率则明显减少，仅为7．69％，并且均呈现出统计学差异（P〈0.05）。结论低分子肝素联合尿激酶对急性心肌梗死患者临床治疗效果的改善具有极其重要的临床意义。     

The difficult balance between thrombosis and bleeding after transcatheter aortic valve replacement: A translational review

The difficult balance between thrombosis and bleeding after transcatheter aortic valve replacement. TAVR: transcatheter aortic valve replacement.