吸入型胰岛素研究进展

随着胰岛素(Ins)新剂型的不断问世，其给药途径和方法已从传统的皮下注射法，发展到连续皮下注射法(胰岛素泵)．它具有基本能模拟正常人胰岛β细胞的生理性释放，但由于皮下注射带来的痛苦与不便，使许多患者对长期Ins治疗的依从性降低。因此，近年来Ins的新给药途径和新剂型的开发已成为临床和药剂学领域研究的热点。目前，新型吸     

胰岛素给药途径的研究进展

近年来，随着DNA重组技术的发展及人工胰岛素(INS)的合成成功，INS正由单一的注射剂向非注射给药和可调式给药方向发展。现将INS给药途径的进展作一综述。     

胰岛素在糖尿病治疗中给药途径的进展

胰岛素是最有效的治疗糖尿病药物之一,对有效控制血糖,保护胰岛β2细胞功能,预防、延缓糖尿病并发症的发生,提高患者生活质量,都具有极其重要的意义.随着研究的深入,胰岛素的给药途径也有了很多变化,现将胰岛素在糖尿病治疗中给药途径的进展情况综述如下.     

胰岛素注射工具的研制进展

随着胰岛素的发现,糖尿病的治疗发生了划时代的转变,人们对糖尿病的认识、糖尿病及并发症的控制和研究进入了一个新的历史时期,由对降低糖尿病病死率的关心转向对如何使用胰岛素和口服降糖药来提高患者生活质量的关注。胰岛素是一种含有51个氨基酸的蛋白质多肽,对于肠道的蛋白酶和pH非常敏感,因其可以造成胰岛素的变性和分解,故外源胰岛素不能通过口服给药,皮下注射是最通常的给药途径,最方便用于临床治疗。在糖尿病急性代谢紊乱等急性高血糖时可以静脉内给药和肌肉注射;腹腔内给药最接近内源胰岛素运送,但只在透析等特殊情况下使用;鼻内喷…     

基层医院皮下注射胰岛素的细节管理

胰岛素注射给药途径主要为静脉注射和皮下注射,2006年以来,我科通过做好胰岛素注射前准备、病人宣教,规范医嘱处理,胰岛素的安全贮存和护士的培训等细节管理,从而保证了胰岛素时安全有效。     

以多烷基氰化丙烯酸盐微粒胶囊作为胰岛素药物载体的口服新法方

为了寻找用胰岛素治疗Ⅰ型糖尿病的最好给药途径,过去曾有人试用鼻腔或直肠给药及把胰岛素包被上非渗透性薄膜或脂质体口服,但效果均不好。作者以多烷基氰化丙烯酸盐微粒胶囊作为胰岛素的药物载体,口服观察对患糖尿病的和正常的Wister大鼠的疗效,并与皮下注射途径进行了比较。 材料和方法 微粒胶囊采用异丁基氰化丙烯酸盐的界面乳剂     

影响急性脑梗死溶栓治疗效果的因素

急性脑梗死溶栓治疗的临床疗效和安全性一直未能获得一致意见。许多问题，如溶栓药物的选择，给药时间和给药途径等尚存在争议。文章综述了影响溶栓治疗效果的因素。     

口服胰岛素研究进展

胰岛素 (Insulin)是治疗糖尿病的一个重要药物 ,尤其是治疗 1型糖尿病的必备药物。有学者在 1 997年报道 ,胰岛素的给药方式最主要的是通过皮下注射途径 ,另外大约有 1万到 2万病人是通过胰岛素泵途径 [1 ] 。上述传统的胰岛素给药方法与正常的药代动力学过程不同 ,经皮下和静脉注射后先经毛细血管、静脉系统回心脏 ,再经动脉系统到肝脏代谢及全身各效应细胞发挥作用 ,使胰岛素在外周血管滞留较长 ,不能模仿生理性胰岛素分泌。而体内胰岛素从胰岛 β细胞分泌后经门脉系统到肝脏代谢 ,经下腔静脉回心脏 ,再经动脉系统到全身各效应细胞发挥作…     

甘精胰岛素经皮超声导入与皮下注射的疗效比较

目的 探讨甘精胰岛素经皮超声导入的降糖效果。方法将43例T2DM患者随机分组，分别采用经皮超声导人甘精胰岛素和皮下注射甘精胰岛素两种不同方法控制血糖，自身前后交叉对照，评价经皮超声导入甘精胰岛素的降糖效果，比较不同给药方式所需的胰岛素剂量。结果甘精胰岛素采用经皮超声导入和皮下注射两种不同的给药方式，对空腹及餐后血糖的控制无统计学差异（P〉0．05），不同给药方式所需甘精胰岛素剂量具有统计学差异（P〈0．05）。结论经皮超声导入甘精胰岛素以及皮下注射甘精胰岛素两种给药方式均能有效控制血糖。在达到同样降糖目标的情况下，经皮超声导入所需甘精胰岛素剂量较皮下注射增多15％左右。     

胰岛素直肠给药:一种有效的降血糖制剂

胰岛素通过胃肠道途径给药的方法,由于其具有潜在的临床价值,曾有人作了若干努力。当时,采用口腔给药方法,取得了一定的效果,唯其吸收作用没有规律且不可靠,因此即没能应用于临床,也不适用于实验。由于直肠相对来说缺乏消化酶,所以胰岛素直肠给药的蛋白降解作用,至少在一个短时间内不会发生。作者早先的实验表明:给予患者无表面活性剂的直肠用CZI胰岛素,当其剂量为每公斤体重10单位时,患者的葡萄糖和胰岛素水平都未发生明显的变化。因此,作者在本研究中,着重探     

Subcutaneous versus intraperitoneal administration of insulin on post-prandial hyperglycaemia and glucose turnover in alloxan diabetic dogs

Summary The effects of subcutaneous and intraperitoneal insulin delivery by a closed-loop insulin infusion device on post-prandial hyperglycaemia and rates of glucose appearance and disappearance were compared in alloxan diabetic dogs. No differences in basal or post-prandial values or patterns of response were observed between the two routes of insulin delivery. In addition, the amounts of insulin infused and the plasma insulin concentrations achieved were not different for the two routes of insulin administration. These studies demonstrate that in the dog there appears to be no difference in the pattern of disposal of glucose from a mixed meal when insulin was administered intraperitoneally or subcutaneously at the rates of insulin infusion used in these experiments. Key words: Subcutaneous insulin, intraperitoneal insulin, glucose turnover, diabetic dogs.     

Waiting to inhale: Noninjectable insulin,are we there yet?

Subcutaneous injection has been the only route of insulin administration for patients with type 1 or type 2 diabetes for the past 80 years. Although research and development in this time has improved the insulin treatments themselves, it is only now that alternative routes of insulin administration are becoming viable. Many avenues of insulin administration have been explored, including oral, buccal, and pulmonary routes. However, these methods of noninvasive insulin delivery are not free from difficulties and only preliminary data are available for oral insulin pills and buccal insulin sprays. The most promising alternative route of delivery appears to be inhaled insulin and two devices are already in phase III testing. Nevertheless, inhaled insulin devices will still have to overcome some problems and recent studies show that these challenges are currently being confronted. It appears that years of research into noninvasive methods of insulin administration are close to fruition and this review outlines the most recent findings in this area.     

Unlocking the opportunity of tight glycaemic control. Innovative delivery of insulin via the lung

As the incidence of diabetes reaches epidemic proportions, the use of new, alternative routes of insulin delivery to manage glycaemic control is becoming an ever more active area of research. The high permeability and large surface area of the lung make it an attractive alternative to subcutaneous (SC) insulin injections. This review discusses the technical factors that influence the efficacy of pulmonary drug delivery and describes how an appreciation of these issues has enabled the design of Exubera, a novel, non-invasive, pulmonary dry-powder human insulin delivery system currently in development by Pfizer and the Sanofi-Aventis Group in collaboration with Nektar Therapeutics. While clinical trials of this novel aerosol delivery of insulin are still ongoing in patients with diabetes, the results so far suggest it is simple to use and can provide reproducible doses of insulin in therapeutic amounts with only a few inhalations per dose. In addition, it has been shown to be comparable in terms of efficacy and safety to a conventional SC insulin injection regimen. Delivering aerosolized drugs via the lungs avoids the necessity for SC injections and thereby may increase the patient's acceptability of an insulin-based therapeutic regimen.     

Alternative routes of insulin delivery.

Attempts at replicating physiological insulin secretion, as a means of restoring the normal metabolic milieu and thereby minimizing the risk of diabetic complications, has become an essential feature of insulin treatment. However, despite advances in the production, purification, formulation and methods of delivery of insulin which have occurred in recent years, this has met with limited success. The current advocacy of intensive insulin therapy regimens involving multiple daily subcutaneous injection places a heavy burden of compliance on patients and has prompted interest in developing alternative, less invasive routes of delivery. To date, attempts to exploit the nasal, oral, gastrointestinal and transdermal routes have been mainly unsuccessful. The respiratory tree, with a large surface area, offers the greatest potential for the delivery of polypeptide drugs and there is renewed interest in administrating insulin by the intrapulmonary route. Current pulmonary drug delivery systems include a variety of pressurized metered dose inhalers, dry powder inhalers, nebulizers and aqueous mist inhalers. Recent clinical studies suggest a possible role for inhaled insulin in fulfilling meal-related insulin requirements in persons with Type 1 and Type 2 diabetes. Most experience with inhaled insulin has been obtained using either dry powder formulation in the Nektar Pulmonary Inhaler/Exubera device (Nektar Therapeutics Inc., San Carlos, CA, Aventis, Bridgewater, NJ, Pfizer, NY) or a liquid aerosol formulation in the AERx Insulin Diabetes Management System (Aradigm Corp., Hayward, CA, NovoNordisk A/S, Copenhagen, Denmark). If long-term safety and efficacy is confirmed, inhalation may become the first non-subcutaneous route of insulin administration for widespread clinical use. Despite overwhelming interest and investment in administering insulin via the oral route, success is not expected in the short term. Attempts at utilizing the buccal mucosa and skin are also continuing. Pancreatic transplantation will remain limited to those patients receiving a kidney transplant and immunotherapy. Islet cell transplantation is at an early though encouraging stage following the availability of new less toxic immunosuppressive agents. True insulin independence will require further advances in the combined fields of cell biology and genetics to ensure freedom from both the need for lifelong administration of insulin and the complications of diabetes.     

Insulin's 85th anniversary--An enduring medical miracle

In 1922, the discovery of insulin led to a revolution in diabetes management. Since then, many improvements have been made to insulin preparations: early preparations of bovine and porcine insulins were purified and their duration of action prolonged, giving rise to the introduction of Neutral Protamine Hagedorn (NPH) insulin and monocomponent insulins. Then, with the advances in genetic engineering in the 1980s, it became possible to produce recombinant human insulin. Nowadays, modern molecular biology techniques enable the production of insulin analogues, which have several advantages over human insulin preparations including a reduced risk of hypoglycaemia. Insulin delivery is still predominantly via subcutaneous injections, but alternative routes of insulin administration are being investigated. Pulmonary delivery has emerged as the most feasible option thus far but oral delivery is an ultimate goal, although basic problems of insulin stability in the gut and absorption from the gastrointestinal tract still need to be resolved. The availability of a true artificial pancreas by means of a closed-loop system, linking continuous glucose monitoring with insulin-pump technology, would also constitute a significant advance, but major technological problems still need to be overcome.     

Unlocking the opportunity of tight glycaemic control. Inhaled insulin: clinical efficacy

Numerous attempts have been made to develop novel routes of insulin delivery that are both effective and tolerable. Of all the potential non-invasive delivery options, pulmonary delivery is the most clinically viable. Early studies demonstrate that the inhaled insulin is rapidly absorbed and is closer to biological insulin than standard subcutaneous insulin (SC). To date, inhaled insulin (Exubera) has been clinically assessed in more than 3500 patients with type 1 or type 2 diabetes, some treated for more than 7 years. Several phase 3 studies of 24-week duration have demonstrated comparable glycosylated haemoglobin (HbA1c) control in patients with type 1 diabetes treated with Exubera vs. SC insulin. Similar results have also been recorded in patients with type 2 diabetes. Furthermore, Exubera has shown clinical superiority to oral agent regimens in patients with type 2 diabetes who failed to achieve their target HbA1c using lifestyle modification and oral agents. Exubera was well tolerated and treatment satisfaction was high, with Exubera being the preferred insulin therapy in all studies. The results of these trials, and others, suggest that Exubera may be a valuable tool to help a wide variety of patients with type 1 or type 2 diabetes reach their recommended goals for glycaemic control, irrespective of their current therapy.     

Pharmacokinetic Model of the Transport of Fast-Acting Insulin From the Subcutaneous and Intradermal Spaces to Blood

Pharmacokinetic (PK) models describing the transport of insulin from the injection site to blood assist clinical decision making and are part of in silico platforms for developing and testing of insulin delivery strategies for treatment of patients with diabetes. The ability of these models to accurately describe all facets of the in vivo insulin transport is therefore critical for their application. Here, we propose a new model of fast-acting insulin analogs transport from the subcutaneous and intradermal spaces to blood that can accommodate clinically observed biphasic appearance and delayed clearance of injected insulin, 2 phenomena that are not captured by existing PK models. To develop the model we compare 9 insulin transport PK models which describe hypothetical insulin delivery pathways potentially capable of approximating biphasic appearance of exogenous insulin. The models are tested with respect to their ability to describe clinical data from 10 healthy volunteers which received 1 subcutaneous and 2 intradermal insulin injections on 3 different occasions. The optimal model, selected based on information and posterior identifiability criteria, assumes that insulin is delivered at the administrative site and is then transported to the bloodstream via 2 independent routes (1) diffusion-like process to the blood and (2) combination of diffusion-like processes followed by an additional compartment before entering the blood. This optimal model accounts for biphasic appearance and delayed clearance of exogenous insulin. It agrees better with the clinical data as compared to commonly used models and is expected to improve the in silico development and testing of insulin treatment strategies, including artificial pancreas systems.     

Insulins today and beyond

The advent of insulin almost 80 years ago revolutionised treatment of diabetes and must be one of the most outstanding achievements of twentieth century medicine. Since then, there has been an ever-increasing awareness and acceptance of the need to achieve and sustain near-normoglycaemia to delay onset and retard progression of diabetic angiopathy. Physiological insulin replacement is therefore central to management of patients with diabetes who are unable to make [corrected] insulin. Insulin formulations, treatment strategies, and methods and routes of delivery have changed much, with more and more options for monitoring the effect on blood glucose concentrations. Patients with type 1 and type 2 diabetes need insulin much more aggressively than previously. Parallel developments in glucose-sensing technologies are welcomed as an integral part of safe and optimum implementation of insulin replacement therapy.     

Unlocking the opportunity of tight glycaemic control. Promise ahead: the role of inhaled insulin in clinical practice

The attainment and maintenance of good glycaemic control in both type 1 and type 2 diabetes are major challenges. The main (perceived) barriers of therapy are poor compliance with prescribed medication, hypoglycaemia, fear of insulin injection and fear of self-testing by finger pricking. Another major issue is the acceptance and uptake of new insulin-delivery systems and routes of administration. Insulin therapy regimens and insulin preparations are nowadays often chosen because of the ease of delivery. The use of inhaled insulin may, because of the relative ease of administration, facilitate the transfer of type 2 diabetes patients from tablets to insulin, especially in patients with fear or phobia of needles. However, non-injectable insulin will not automatically be preferred to subcutaneous (SC) insulin injections and a proper assessment of patient acceptance and preference is of great importance. Recent studies suggest that patients may prefer inhaled insulin (Exubera) over SC insulin. Thus, the availability of inhaled insulin as a potential treatment may increase a patient's willingness to add or change to more appropriate diabetes therapy, which includes insulin. Future studies should be targeted at specific groups of patients who may benefit the most from inhaled insulin, such as those with type 2 diabetes who are delaying initiation or intensification of insulin injections.