提高蛋白质及多肽类药物肺部给药生物利用度的方法及其作用机制

目的介绍国内外提高蛋白质与多肽类药物肺部给药系统生物利用度的方法及其作用机制的最新研究进展。方法对国内外最新发表的相关文献进行分析、整理和综合。结果吸收促进剂、酶抑制剂及脂质体均可使蛋白质及多肽类药物的肺部吸收明显提高,甚至达到治疗所需的生物利用度。结论蛋白质及多肽类药物的肺部给药系统具有广阔的应用前景。     

蛋白质和多肽类药物口服给药研究进展

蛋白质和多肽类药物具有良好的选择性和生物活性,已成为治疗众多疾病的首选药物。由于胃肠道内酶的降解作用以及肠道粘膜的低通透性,蛋白质和多肽类药物口服生物利用度极低,其常规给药一直以注射为主。为了使蛋白质和多肽类药物能够广泛应用于临床,研究人员对蛋白质和多肽类药物口服给药系统做了大量研究。目前用于提高蛋白质和多肽类药物口服生物利用度的方法主要有微粒给药系统、内源性细胞转运系统、应用酶抑制剂和黏附给药系统等。文章就这些方法在蛋白质和多肽类药物口服给药中的应用进行了综述。     

蛋白多肽类药物纳米粒口服给药系统的研究进展

目的综述近年来纳米粒作为蛋白质多肽类药物口服传递系统方面的研究现状和进展。方法分析有关文献资料,从纳米粒给药系统的载体材料、口服药效等方面进行了概述。结果纳米粒给药系统可提高蛋白质和多肽类药物的口服吸收效率,提高此类药物的生物利用度。结论纳米粒给药系统在口服传递蛋白质和多肽类药物方面有着广阔的研究和应用前景。     

蛋白质及多肽药物的药剂学研究进展

蛋白质及多肽类药物的体内过程存在的特殊情况，因而为制剂与生物药剂学研究提出了新课题，新给药途径的研究，本文重点介绍了鼻腔给给与肺部给药，长效脂质本，蛋白质及多肽类药物的吸收促进剂以及一些符合时辰节律的药物释放系统如按需给药系统，脉冲释药系统与自我调节系统等。     

多肽与蛋白质类药物给药系统的研究现状

综述了多肽与蛋白质类药物给药系统研究的现状，着重介绍了该类药物给药系统研究的特点，及提高其非注射给药生物利用度的方法。     

多肽及蛋白质类药物肺部给药的现状与展望

肺部给药与传统的注射给药及其他一些给药途径相比,在患者顺应性和生物利用度方面具有明显的优势,目前已有数种肺部给药制剂进入临床研究阶段。多肽及蛋白质类药物的肺部给药具有诱人的发展前景。     

蛋白质和肽类药物的口服胃肠道吸收机理

随着生物技术的发展 ,出现了许多用于预防和治疗疾病的多肽和蛋白质药物。蛋白质类药物目前市场总值逾 1 5 0多亿美元。其中肽类药物的销售额超过 2 0亿美元。因此 ,几家公司正重点开发蛋白质和肽类药物新的给药系统。开发给药系统是人们最乐于接受的一种给药方式 ,然而由于多肽与蛋白质类药物特殊的理化性质 ,此类药物口服后吸收差 ,生物利用度低。加之此类药物的t1/2 较短 ,故需频繁注射给药 ,给病人带来极大的痛苦和不便 ,因此 ,蛋白质和肽类药物新的给药途径的研究成为热点。其中口服给药途径的研究尤其重要 ,研究口服后胃肠吸收障碍及…     

蛋白质类药物胃肠道促吸收方法的研究进展

目的:介绍蛋白质类药物胃肠道促吸收方法的研究进展,为开发蛋白质类药物的胃肠道给药系统提供参考。方法:根据文献,对促进蛋白质类药物胃肠道吸收的技术手段和剂型手段进行了综述。结果与结论:采用添加酶抑制剂与吸收促进剂,对蛋白质进行化学修饰,利用穿膜肽、转铁蛋白等特殊转运机制的技术手段,以及采用纳米粒、微乳、脂质体、水凝胶等剂型手段,均可有效提高蛋白质类药物的胃肠道吸收,提高其生物利用度。     

多肽类药物口服吸收的研究进展

多肽类药物对癌症、自身免疫性疾病具有良好的治疗前景。目前，市售肽类制剂以注射剂为主，频繁的注射给患者造成很大的痛苦。口服作为一种方便、顺应性好的给药途径，日益成为研究焦点；然而肽类药物口服受消化道屏障限制，生物利用度低，半衰期短，制约了它的发展。提高多肽类药物口服生物利用度的研究工作业已展开。本文综述了限制肽类药物口服吸收的主要影响因素及针对性的解决策略。     

蛋白多肽类药物非注射给药途径的研究

目的:概述近年来蛋白多肽类药物各种非注射给药途径的特点及研究进展。方法:通过比较蛋白多肽类药物口服、鼻腔、口腔粘摸、肺部吸入、透皮吸收等给药途径的特点及研究进展,剖析各种给药途径的优劣势及存在的问题。结果:由于蛋白多肽类药物本身的化学性质及人体各个部位的生理结构特点不同,各种非注射给药途径存在的问题也各不相同。结论:针对口服、鼻腔、口腔粘膜、肺部、皮肤等吸收途径的特点,选择适合蛋白多肽类药物特点的给药途径,能为人类防治疾病取得更好的治疗效果。     

提高蛋白质及肽类药物口服生物利用度的方法

论述了有关蛋白质和肽类药物口服吸收研究的新进展，包括该类药物口服吸收的机理、吸收部位及口服吸收生物利用度低的原因，重点讨论了改善蛋白质和肽类药物口服生物利用度的方法。     

聚乙二醇化蛋白质多肽类药物定点修饰策略

聚乙二醇修饰具有抵抗蛋白酶降解、提高稳定性、延长体内半衰期、降低免疫原性等优点,能够有效地改善蛋白质多肽类药物的临床药效。而聚乙二醇的定点修饰由于能够获得均一性和高活性保留率的产物,并能提高产物的产率,已经引起了广泛关注。本文概述近年来聚乙二醇定点修饰蛋白质多肽类药物方面的研究进展,并对聚乙二醇定点修饰技术的发展趋势进行了展望。     

Emerging trends in oral delivery of peptide and protein drugs

Most peptide and protein drugs are currently used as parenteral formulations because of their poor oral bioavailability. Development of an effective oral delivery system for these macromolecular drugs requires a thorough understanding of their physicochemical properties, such as molecular weight, hydrophobicity, ionization constants, and pH stability, as well as biological barriers that restrict protein and peptide absorption from the gastrointestinal (GI) tract, including pH variability, enzymatic degradation, and membrane efflux. Various strategies currently under investigation include amino acid backbone modifications, formulation approaches, chemical conjugation of hydrophobic or targeting ligand, and use of enzyme inhibitors, mucoadhesive polymers, and absorption enhancers. However, there is only limited success because of the hostile environment of the GI tract--e.g., strong pH extremes and abundant presence of potent luminal enzymes. This review focuses on the challenges posed by the GI system and how different pharmaceutical approaches can be used to make oral delivery of protein and peptide drugs more feasible. The roles of P-glycoprotein and CYP3A4 in controlling the extent of intestinal absorption and metabolism will also be discussed.     

Control of pulmonary absorption of drugs by various pharmaceutical excipients

In general, drugs are well absorbed from the lung, and the pulmonary absorption of therapeutic protein and peptide drugs, which are poorly absorbed from the gastrointestinal tract, was observed. However, locally acting drugs including antiasthmatic agents, bronchodilators, and expectorants should be localized for a long period in the lung tissues. In this study, the effects of various viscous vehicles on the absorption of theophylline and fluticasone propionate after intrapulmonary administration were examined in rats. Carrageenans were effective in regulating the absorption rate of these drugs. On the other hand, the bioavailability of therapeutic protein and peptide drugs with relatively high molecular weights from the pulmonary route is still poor when compared with the parenteral route. Therefore we examined the effects of chitosan and chitosan oligomers on the pulmonary absorption of interferon-alpha and salmon calcitonin in rats. Chitosan oligomers were effective in improving the pulmonary absorption of these drugs, and chitosan hexamer appeared to be markedly more effective than other oligomers. Furthermore, the present study indicated that chitosan oligomers did not cause any membrane damage to rat pulmonary tissues. In conclusion, it is suggested that various pharmaceutical excipients achieved the sustained pulmonary absorption of locally acting drugs and the improved pulmonary bioavailability for therapeutic protein and peptide drugs.     

Improvement of transmucosal absorption of biologically active peptide drugs]

Peptide and protein drugs are becoming a very important class of therapeutic agents. However, the oral bioavailability of peptide and protein drugs is generally poor because they are extensively degraded by proteases in the gastrointestinal tract or impermeable through the intestinal mucosa. For the systemic delivery of the peptide and protein drugs, parenteral administration is currently required to achieve their therapeutic activities. However, this administration is poorly accepted by patients and may cause allergic reactions and serious side effects. Therefore, various approaches have been examined to overcome the delivery problems of these peptides when they are administered into the gastrointestinal tract and other mucosal sites. These approaches include (1) to use additives such as absorption enhancers and protease inhibitors, (2) to develop an administration method for peptides that can serve as an alternative to oral and injection administration, (3) to modify the molecular structure of peptide and protein drugs to produce prodrugs and analogues, and (4) to use the dosage forms to these peptide drugs. In this study, we demonstrated that the transmucosal absorption of various peptides including insulin, calcitonin, tetragastrin and thyrotropin releasing hormone (TRH) could be improved by the use of these approaches. Therefore, these approaches may give us basic information to improve the transmucosal absorption of peptide and protein drugs.     

多肽药物口服给药的研究进展

在疾病的治疗中多肽药物具有显著的优越性,但是其口服生物利用度低,导致多肽药物局限于注射给药,因而顺应性较差。目前,在研究多肽口服给药研究中已投入大量工作。本文综述了多种实现多肽口服给药的方法。     

Oral peptide and protein delivery: intestinal obstacles and commercial prospects

Introduction: Pharmaceutical research and development is increasingly focussed on biopharmaceuticals including peptide and protein drugs. Despite their growing importance and almost 100 years of research, the vast majority are still only available by injection. Oral bioavailabilities of peptide and protein drugs are very low mainly because of the stability and permeability barriers of the gastrointestinal (GI) tract.

Areas covered: Data from studies of peptide/protein drug oral bioavailability, stability and permeability in the stomach, small intestine and large intestine have been compiled to make comparisons between the various regions of the GI tract and peptides/proteins with differing characteristics. Assessment of the oral formulation strategies that have progressed farthest in clinical trials has been conducted to identify which have the best potential for future success.

Expert opinion: Oral delivery of peptides and small proteins is increasingly achieved by utilising formulations that combat the stability challenges of the GI tract and disrupt the intestinal cell membranes to enable absorption. However, oral bioavailabilities remain low and variable therefore high, potentially toxic doses of peptide/protein drugs are needed to elicit a therapeutic effect leading to high cost of the final product. There is very little research into larger proteins, making their oral delivery unlikely in the near future.     

Converting a peptide into a drug: strategies to improve stability and bioavailability

The discovery of peptide hormones, growth factors and neuropeptides implicated in vital biological functions of our organism has increased interest in therapeutic use of short peptides. However, the development of peptides as clinically useful drugs is greatly limited by their poor metabolic stability and low bioavailability, which is due in part to their inability to readily cross membrane barriers such as the intestinal and blood-brain barriers. The aim of peptide medicinal chemistry is, therefore, to develop strategies to overcome these problems. Recent progress in chemical synthesis and design have resulted in several strategies for producing modified peptides and mimetics with lower susceptibility to proteolysis and improved bioavailability, which has increased the probability of obtaining useful drugs structurally related to parent peptides. This review describes different experimental approaches to transforming a peptide into a potential drug and provides examples of the usefulness of these strategies.