Nasal and pulmonary drug delivery systems

The respiratory route of administration has long been the medically desired drug delivery portal for the administration of topical anti-inflammatory drugs. These drugs are administered either to the lung, i.e., the lower respiratory system to treat asthma, or to the nasal cavity, i.e., the upper respiratory system to treat allergic rhinitis. This therapeutic focus dominates the drug delivery applications for the respiratory system. More recently, the respiratory system has provided a non-invasive method for the administration of biotherapeutics. And finally, formulation and device advancements have led to the consideration of the respiratory route for a number of other therapeutic applications where systemic delivery is desirable. All of these factors have resulted in the therapeutic patents that are discussed in this review.     

Gentamicin and leucine inhalable powder: What about antipseudomonal activity and permeation through cystic fibrosis mucus?

The aim of this study was to evaluate the permeation properties of gentamicin (G) in a novel dry powder form for inhalation through an artificial mucus model. Moreover, since respiratory infections sustained by Pseudomonas are a major cause of sickness and death in CF patients, the susceptibility of P. aeruginosa to engineered G powders was investigated.     

小分子糖负载血小板+冻干保护剂混合悬液的相变点测定与屏蔽实验研究

目的测定冻干血小板长期保存预冻程序和所依据的制品相变点温度并摸索相应屏蔽相变点的最佳冷冻曲线。方法研制出小分子糖负载血小板+冻干保护剂混合悬液,使用速率程序降温仪分析测定该混合悬液样品的相变点温度;根据测得的相变点温度,设计屏蔽相变点的预冻程序,根据温度变化曲线,判断相变点屏蔽结果。结论该混合悬液样品的相变点温度为(-13.56±2.05)℃;据此相变点温度所设计的3种相应的屏蔽相变点的预冻程序中,程序3为最佳冷冻曲线。结果获得了小分子糖负载血小板+冻干保护剂混合悬液的相变点温度及相应的屏蔽相变点的最佳预冻程序。     

A new respirable form of rifampicin

The aim of this research was to investigate a novel dry powder formulation of rifampicin (RF) that presents an improved lung deposition profile by means of a polymorphic transformation into a flake-like crystal hydrate. Rifampicin dihydrate (RFDH) was prepared by recrystallization of RF in anhydrous ethanol. A control formulation, amorphous RF (RFAM) was prepared by spray drying. The physicochemical properties of the RFDH and the RFAM were characterized. Aerosol performances of RFDH and RFAM were studied with two dry powder inhalers (DPIs), an Aerolizer® and a Handihaler®, using a Next Generation Impactor (NGI). The RFDH powder was successfully prepared using simple recrystallization process and had a MMAD of 2.2 μm. The RFDH powders were characterized as having a very thin flaky structure; this unique morphology provided improved aerosolization properties with a decreased device dependency upon aerosolization. The flaky morphology of RFDH resulted in a reduced agglomeration tendency than that of spherical RFAM particles. The maximum fine particle fraction (FPF_TD) of 68% for the RFDH was achieved with the Aerolizer® device. Significant chemical degradation was not observed from the RFDH, while the RFAM showed significant chemical degradation at 9 months. The excipient-free formulation of the RFDH offers the benefit of delivering a maximum potency formulation, of the antibiotic, directly to the site of infection, the lung.     

Stable dry powder inhaler formulation of tranilast attenuated antigen-evoked airway inflammation in rats

Tranilast (TL) has been clinically used for the treatment of airway inflammatory diseases, although the clinical use of TL is limited because of its poor solubility and systemic side effects. To overcome these drawbacks, a novel respirable powder of TL (CSD/TL-RP) for inhalation therapy was developed using nanocrystal solid dispersion of TL (CSD/TL). Stability study on CSD/TL-RP was carried out with a focus on inhalation performance. Even after 6 months of storage at room temperature, there were no significant morphological changes in micronized particles on the surface of carrier particles as compared with that before storage. Cascade impactor analyses on CSD/TL-RP demonstrated high inhalation performance with emitted dose and fine particle fraction (FPF) of ca. 98% and 60%, respectively. Long-term storage of CSD/TL-RP resulted in only a slight decrease in FPF value (ca. 54%). Inhaled CSD/TL-RP could attenuate antigen-induced inflammatory events in rats, as evidenced by marked reduction of granulocytes in bronchoalveolar lavage fluid and inflammatory biomarkers such as eosinophil peroxidase, myeloperoxidase, and lactate dehydrogenase. These findings were consistent with decreased expression levels of mRNAs for nuclear factor-kappa B and cyclooxygenase-2, typical inflammatory mediators. Given these findings, inhalable TL formulation might be an interesting alternative to oral therapy for the treatment of asthma and other airway inflammatory diseases with sufficient dispersing stability.     

不同比重干化学检测尿蛋白结果分析

目的分析不同比重下尿蛋白干化学定性结果与全自动生化分析仪定量结果,探讨尿比重对干化学检测尿蛋白的影响。方法 844份尿标本先经干化学检测尿蛋白,再用全自动生化分析仪定量检测尿微量白蛋白、尿肌酐,计算微量白蛋白/肌酐比值(UACR),统计分析不同比重下尿蛋白定性与定量结果。结果当干化学尿蛋白结果为阴性时,随着尿比重的增加,假阴性率下降,当1.030≤比重≤1.005时,假阴性率从34.1%下降到2.7%;当干化学尿蛋白结果为阳性时(±～+++),比重越高,假阳性率越高,随着比重下降,假阳性下降,比重≤1.005时没有假阳性。结论尿比重能明显影响干化学检测尿蛋白的准确性,对于比重过低或过高的标本,可以检测UACR或24h尿蛋白定量进行鉴别。     

干式生化分析仪在冠心病患者中的应用价值

目的探讨干式生化分析仪在冠心病(CHD)患者中的应用价值,分析CHD患者血浆心肌酶变化的临床意义。方法采用干式生化分析仪检测60例CHD患者心肌酶的变化,动态观察其变化规律。结果 CHD患者心肌酶明显高于健康对照组,差异有统计学意义(P0.01),心肌损伤程度与血浆中酶的活力呈正相关。结论应用干式生化分析仪检测心肌酶可快速准确地诊断CHD,并对其治疗和预后有指导意义。     

Tooth‐to‐Implant Connection: A Systematic Review of the Literature and a Case Report Utilizing a New Connection Design

Background: In the treatment of partially edentulous patients, implants have often been connected to natural teeth. Numerous studies have reported significant complications and problems, while others have demonstrated favorable outcomes. Purpose: The purpose of this article was to systematically review the literature regarding the splinting of implants and teeth. The difference in the biomechanical behavior between osseointegrated implants and teeth and the efficacy of the different modes of connection that have been employed are explored. Materials and Methods: A MEDLINE search between 1966 and October 2006 was performed to retrieve relevant articles. A further manual search from the bibliographies of the former articles was performed to include as many references as possible. Prospective and retrospective clinical studies, as well as laboratory and computer‐generated research, were included. Results: A pronounced difference in the biomechanics of teeth and implants has been revealed in theoretical models. This disparity has also been supported by the majority of the experimental work published. As a result, principal complications, such as intrusion of teeth and higher risk of overload and greater marginal bone loss around the implants have been reported. Among the several types of connections utilized, the rigid connection showed fewer complications but unfortunately did not eliminate them. Conclusion: Totally implant‐supported prostheses should be the treatment of choice. However, there are cases where combining teeth and implants is inevitable. The authors propose a rationale design of connecting implants and teeth. This design minimizes the biologic and technical complications.     

儿童春季卡他性角结膜炎与干眼症相关性分析

目的:探讨春季卡他性角结膜炎患儿的泪膜功能,并分析其与儿童干眼症发生的相关性。方法:取临床诊断为春季卡他性角结膜炎的86例患儿作为观察组,取年龄与之匹配的正常儿童86例作为对照组,分别做基础泪液分泌试验(schirmer Itest)、泪膜破裂时间(BUT)、角膜荧光素(FL)染色检查。结果:儿童春季卡他性角结膜炎常合并干眼症的相关症状:瞬目次数增加(33%),干涩感(14%),烧灼感(10%)。观察组泪膜功能相关检查:双眼泪液分泌试验均低于对照组(P=0.01),双眼泪膜破裂时间短于对照组(P<0.01),双眼角膜荧光素染色评分高于对照组(P<0.01)。泪膜功能改变与疾病严重程度有关,与病程、亚型分类无关。结论:春季卡他性角结膜炎患儿泪膜功能发生改变,是干眼症的易患人群。