四肺部吸给药系统课件.pptVIP

四、肺部吸入给药系统 优点：面积, 上皮细胞间隙，肺泡、血管和淋 巴管，血流速度，无首过破坏、无促 进剂系统 限制和要求：沉着部位及重现性、长期毒性 Inhalation therapy ( Historical perspective ) 1955, Metered-does inhaler ( MDI ) developed by George Maison 1956 marketed , FDA approval May ,1974, Sugarloaf conference milestone in the clinical use of aerosolized drug therapy Inhalation therapy ( Historical perspective ) 1980s-1990s, development and delivery of drug formulation additional device , ↓ oropharyngeal loss dry powder inhaler 2000 Non-CFC propellant medications other than pulmonary disease Macromolecules and Airway Macromolecules airway surface ( 3.0 M2 ) nearly impermeable lung periphery ( alveoli , 80-100 M2 ) do permeate Comparison of therapeutic ratiousing three routes of administration of a hypothetical drug for equivalent therapeutic benefits IV Oral Inhaled units available 100 50 10 to exert effect reaching target tissue 2 1 1 reaching other tissues 98 49 9 therapeutic ratio 1/49 1/49 1/9 ( effective drug / drug acting at other tissue ) Inhalable drug for systemic therapy Efficiently deliver to the lung periphery Reproducible therapeutic drug dose Accommodate flexible dosing Stable formulation at room Temp. Device must be portable and easy to use Inhalable drug industry today At least 5 companies AeroGen Alkermes Aradigm corporation Dura pharmaceuticals Inhale Therapeutic Systems Known developing inhalable proteins Aventis Bering α-1 proteinase inhibitor for emphysema Biogen AVONEX ( IFNβ-1a) for MS Pfizer , Aventis Pharma inhalable insulin Medical conditions that could benefits from pulmonary delivery Pain Panic and anxiety Anaphylaxis Ca