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。     

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。     

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。     

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。     

制剂新技术在多肽、蛋白质类药物给药系统研究中的应用

目的 介绍制剂新技术在多肽、蛋白质类药物给药系统研究中的应用。方法 综述了多肽、蛋白质类药物的性质特点和影响其稳定性的原因;制剂新技术在多肽、蛋白质类药物给药系统中的运用;对LHRH及其类似物和胰岛素两类药物的新型制剂研究进行了概述。结果 脂质体、微乳和复乳、微球、纳米粒、自控式释药技术等制剂新技术广泛应用于多肽、蛋白质类药物给药系统中,取得了较大进展;黄体激素释放激素(LHRH)及其类似物和胰岛素两类药物的新剂型研究具有代表性且引人注目。结论 将制剂新技术用于多肽、蛋白质类药物给药系统的研究,有着广阔的应用前景。     

制剂新技术在多肽、蛋白质类药物给药系统研究中的应用

目的　介绍制剂新技术在多肽、蛋白质类药物给药系统研究中的应用。方法　综述了多肽、蛋白质类药物的性质特点和影响其稳定性的原因;制剂新技术在多肽、蛋白质类药物给药系统中的运用;对LHRH及其类似物和胰岛素两类药物的新型制剂研究进行了概述。结果　脂质体、微乳和复乳、微球、纳米粒、自控式释药技术等制剂新技术广泛应用于多肽、蛋白质类药物给药系统中,取得了较大进展;黄体激素释放激素(LHRH)及其类似物和胰岛素两类药物的新剂型研究具有代表性且引人注目。结论　将制剂新技术用于多肽、蛋白质类药物给药系统的研究,有着广阔的应用前景     

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。     

口服结肠给药系统的研究进展

口服结肠靶向给药系统(oral colon targetting drug deliv-ery system,OCTDDS))将治疗结肠疾病的药物靶向输送至结肠,不仅降低常规的口服或直肠给药的毒副作用,且能将药物输送至病灶处,减少给药剂量,提高患者的顺应性;还能提高多肽、蛋白等类药物口服给药的生物利用度。笔者将近年有关口服结肠给药系统的研究综述如下。1口服结肠释药系统的应用1.1时控给药根据时辰药理学原理,应用药剂手段使药物在一定的时滞后释放,使之与人的生理周期相匹配,可用于治疗哮喘、高血压、心绞痛、消化道溃疡及风湿性关节炎等具有节律性的疾病。结肠靶向给药…     

口服多肽和蛋白质药物的研究进展

多肽和蛋白质药物由于其特异性高、安全性高的特点已广泛应用于各种疾病的临床治疗,但其主要给药途径是注射给药,降低了患者的依从性。口服作为一种安全性高、依从性强的给药途径逐渐成为研究焦点,但胃肠道的结构组织和生理功能使得多肽和蛋白质药物口服后生物利用度低、半衰期短。口服后多肽和蛋白质药物的吸收成为此类药物口服给药途径开发的瓶颈,但随着技术的发展,近年来对促进多肽和蛋白质药物口服吸收的研究在临床前和临床试验方面均取得较大进展。综述多肽和蛋白质药物口服吸收途径、影响因素、提高多肽和蛋白质药物口服吸收的方法以及相关临床试验的研究进展。     

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。     

Statins therapy: a review on conventional and novel formulation approaches

Background and objective High levels of cholesterol lead to atherosclerosis, a factor predisposing to the development of coronary artery disease. Statin drugs, i.e. HMG‐CoA reductase inhibitors, have been known since the end of the last century for their benefits against cardio‐ and cerebrovascular diseases and are widely used clinically. This review aims at compiling the research inputs being made for developing therapeutically efficacious dosage forms that have the potential to surmount the limitations of conventional dosage forms of statins. Key findings Statin drugs can reduce the endogenous synthesis of cholesterol and prevent the onset and development of atherosclerosis, and are therefore used as an effective treatment against primary hypercholesterolemia. At present, statin drugs are most often administered orally, on a daily basis. After administration, the bioavailability and the general circulation of statin drugs is fairly low due to the first‐pass metabolism in the liver and clearance by the digestive system. Extensive pharmaceutical research in understanding the causes of low oral bioavailability has led to the development of novel technologies to address these challenges. Summary These technologies vary from conventional dosage forms to nanoparticulate drug‐delivery systems, and have the potential to cause improvements in bioavailability and consequently therapeutic efficacy.     

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.     

多肽类药物的口服吸收及其剂型研究

根据国外有关文献，分析了多肽类药物口服生物利用度低的原因，包括胃肠道黏膜的低渗透性、胃酸和各种消化酶的降解作用及首过效应等，并介绍从结构修饰、处方和剂型设计三方面提高多肽口服生物利用度的方法。     

The use of multifunctional polymers for non-invasive peptide and protein application

For the efficient delivery of peptide and protein drugs by non-invasive routes various strategies have been pursued to overcome enzymatic and mucosal barriers to gain sufficient bioavailability. Among such delivery systems multifunctional polymers have received considerable attention, which is reflected by numerous publications and patents. They are able to provide a controlled release for therapeutic peptides and proteins being embedded in the polymeric network either based on a simple diffusion process or on the biodegradation of the carrier matrix. Additionally, polymers such as polyacrylates display an inhibitory effect towards various proteases located on the absorption membrane. In combination with enzyme inhibitors, this protective effect towards enzymatic attack may further be improved. Moreover, polyacrylates and chitosan display a permeation enhancing effect, in particular for the paracellular uptake of peptide drugs from mucosal tissues. If these polymers also exhibit mucoadhesive properties, the concentration gradient of the drug on the mucosa can be increased and in the case of oral delivery the presystemic enzymatic degradation of the (poly)peptide drug in the intestine between the delivery system and the absorption membrane can be reduced. Delivery systems utilising multifunctional polymers include formulations such as nano- and microspheres, pellets and matrix-tablets.     

pH-Responsive carriers for oral drug delivery: challenges and opportunities of current platforms

Oral administration is a desirable alternative of parenteral administration due to the convenience and increased compliance to patients, especially for chronic diseases that require frequent administration. The oral drug delivery is a dynamic research field despite the numerous challenges limiting their effective delivery, such as enzyme degradation, hydrolysis and low permeability of intestinal epithelium in the gastrointestinal (GI) tract. pH-Responsive carriers offer excellent potential as oral therapeutic systems due to enhancing the stability of drug delivery in stomach and achieving controlled release in intestines. This review provides a wide perspective on current status of pH-responsive oral drug delivery systems prepared mainly with organic polymers or inorganic materials, including the strategies used to overcome GI barriers, the challenges in their development and future prospects, with focus on technology trends to improve the bioavailability of orally delivered drugs, the mechanisms of drug release from pH-responsive oral formulations, and their application for drug delivery, such as protein and peptide therapeutics, vaccination, inflammatory bowel disease (IBD) and bacterial infections.     

Protein drug oral delivery: the recent progress

Rapid development in molecular biology and recent advancement in recombinant technology increase identification and commercialization of potential protein drugs. Traditional forms of administrations for the peptide and protein drugs often rely on their parenteral injection, since the bioavailability of these therapeutic agents is poor when administered nonparenterally. Tremendous efforts by numerous investigators in the world have been put to improve protein formulations and as a result, a few successful formulations have been developed including sustained-release human growth hormone. For a promising protein delivery technology, efficacy and safety are the first requirement to meet. However, these systems still require periodic injection and increase the incidence of patient compliance. The development of an oral dosage form that improves the absorption of peptide and especially protein drugs is the most desirable formulation but one of the greatest challenges in the pharmaceutical field. The major barriers to developing oral formulations for peptides and proteins are metabolic enzymes and impermeable mucosal tissues in the intestine. Furthermore, chemical and conformational instability of protein drugs is not a small issue in protein pharmaceuticals. Conventional pharmaceutical approaches to address these barriers, which have been successful with traditional organic drug molecules, have not been effective for peptide and protein formulations. It is likely that effective oral formulations for peptides and proteins will remain highly compound specific. A number of innovative oral drug delivery approaches have been recently developed, including the drug entrapment within small vesicles or their passage through the intestinal paracellular pathway. This review provides a summary of the novel approaches currently in progress in the protein oral delivery followed by factors affecting protein oral absorption.     

胶体给药在蛋白质多肽类药物中的应用

本文介绍了国内外蛋白质、多肽类药物的新制剂和制剂新技术的研究进展,综述了多肽蛋白质类药物的几种给药剂型,以及胶体给药在蛋白给药方面的发展.     

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。     

Nasal route and drug delivery systems

Nasal drug administration has been used as an alternative route for the systemic availability of drugs restricted to intravenous administration. This is due to the large surface area, porous endothelial membrane, high total blood flow, the avoidance of first-pass metabolism, and ready accessibility. The nasal administration of drugs, including numerous compound, peptide and protein drugs, for systemic medication has been widely investigated in recent years. Drugs are cleared rapidly from the nasal cavity after intranasal administration, resulting in rapid systemic drug absorption. Several approaches are here discussed for increasing the residence time of drug formulations in the nasal cavity, resulting in improved nasal drug absorption. The article highlights the importance and advantages of the drug delivery systems applied via the nasal route, which have bioadhesive properties. Bioadhesive, or more appropriately, mucoadhesive systems have been prepared for both oral and peroral administration in the past. The nasal mucosa presents an ideal site for bioadhesive drug delivery systems. In this review we discuss the effects of microspheres and other bioadhesive drug delivery systems on nasal drug absorption. Drug delivery systems, such as microspheres, liposomes and gels have been demonstrated to have good bioadhesive characteristics and that swell easily when in contact with the nasal mucosa. These drug delivery systems have the ability to control the rate of drug clearance from the nasal cavity as well as protect the drug from enzymatic degradation in nasal secretions. The mechanisms and effectiveness of these drug delivery systems are described in order to guide the development of specific and effective therapies for the future development of peptide preparations and other drugs that otherwise should be administered parenterally. As a consequence, bioavailability and residence time of the drugs that are administered via the nasal route can be increased by bioadhesive drug delivery systems. Although the majority of this work involving the use of microspheres, liposomes and gels is limited to the delivery of macromolecules (e.g., insulin and growth hormone), the general principles involved could be applied to other drug candidates. It must be emphasized that many drugs can be absorbed well if the contact time between formulation and the nasal mucosa is optimized.