Stabilized preparations for use in nebulizers
원문보기
IPC분류정보
국가/구분
United States(US) Patent
등록
국제특허분류(IPC7판)
A61L-009/04
A61F-002/00
A61F-013/00
A61K-009/14
A61K-009/16
출원번호
US-0218213
(1998-12-22)
발명자
/ 주소
Schutt, Ernest G.
Tarara, Thomas E.
Dellamary, Luis A.
Kabalnov, Alexey
Weers, Jeffry G.
출원인 / 주소
Nektar Therapeutics
인용정보
피인용 횟수 :
46인용 특허 :
110
초록▼
Stabilized dispersions are provided for the delivery of a bioactive agent to the respiratory tract of a patient. The dispersions preferably comprise a stabilized colloidal system which may comprise a fluorochemical component. In particularly preferred embodiments, the stabilized dispersions comprise
Stabilized dispersions are provided for the delivery of a bioactive agent to the respiratory tract of a patient. The dispersions preferably comprise a stabilized colloidal system which may comprise a fluorochemical component. In particularly preferred embodiments, the stabilized dispersions comprise perforated microstructures dispersed in a fluorochemical suspension medium. As density variations between the suspended particles and suspension medium are minimized and attractive forces between microstructures are attenuated, the disclosed dispersions are particularly resistant to degradation, such as by settling or flocculation. In particularly preferred embodiments, the stabilized dispersions may be administered to the lung of a patient using a nebulizer.
대표청구항▼
1. A method for the pulmonary delivery of one or more bioactive agents comprising the steps of:providing a stabilized respiratory dispersion comprising one or more bioactive agents wherein the respiratory dispersion comprises a plurality of perforated microstructures suspended in and substantially p
1. A method for the pulmonary delivery of one or more bioactive agents comprising the steps of:providing a stabilized respiratory dispersion comprising one or more bioactive agents wherein the respiratory dispersion comprises a plurality of perforated microstructures suspended in and substantially permeated by a fluorochemical continuous phase wherein the volume of suspension medium displaced by the perforated microstructure is less than 70% of the average particle volume of the perforated microstructure; nebulizing said respiratory dispersion with a nebulizer to provide an aerosolized medicament; and administering a therapeutically effective amount of said aerosolized medicament to at least a portion of the pulmonary passages of a patient in need thereof. 2. The method of claim 1 wherein the mean aerodynamic diameter of the perforated microstructures is between 0.5 and 5 μm.3. The method of claim 1 wherein said perforated microstructures comprise a surfactant.4. The method of claim 3 wherein said surfactant is selected from the group consisting of phospholipids, nonionic detergents, nonionic-block copolymers, ionic surfactants, biocompatible fluorinated surfactants and combinations thereof.5. The method of claim 3 wherein said surfactant is a phospholipid.6. The method of claim 5 wherein said phospholipid is selected from the group consisting of dilauroylphosphatidylcholine, dioleylphosphatidylcholine, dipalmitoylphosphatidylcholine, disteroylphosphatidylcholine, behenoylphosphatidylcholine, arachidoylphosphatidylcholine and combinations thereof.7. The method of claim 1 wherein said bioactive agent is selected from the group consisting of antiallergics, bronchodilators, pulmonary lung surfactants, analgesics, antibiotics, leukotriene inhibitors or antagonists, antihistamines, antiinflammatories, antineoplastics, anticholinergics, anesthetics, anti-tuberculars, imaging agents, cardiovascular agents, enzymes, steroids, genetic material, viral vectors, antisense agents, proteins, peptides and combinations thereof.8. The method of claim 1 wherein said bioactive agent is delivered to the systemic circulation of said patient.9. An inhalation system for the pulmonary administration of a bioactive agent to a patient comprising:a fluid reservoir; a stable respiratory dispersion in said fluid reservoir wherein said stabilized dispersion comprises a fluorochemical continuous phase and a plurality of perforated microstructures comprising at least one bioactive agent suspended in and substantially permeated by the continuous phase wherein the volume of suspension medium displaced by the perforated microstructure is less than 70% of the average particle volume of the perforated microstructure; and a nebulizer operably associated with said fluid reservoir wherein the nebulizer is capable of aerosolizing and discharging the stable respiratory dispersion. 10. The system of claim 9 wherein said perforated microstructures comprise a surfactant.11. The system of claim 10 wherein said surfactant is selected from the group consisting of phospholipids, nonionic detergents, nonionic block copolymers, ionic surfactants, biocompatible fluorinated surfactants and combinations thereof.12. The system of claim 10 wherein said surfactant is a phospholipid.13. The system of claim 12 wherein said phospholipid is selected from the group consisting of dilauroylphosphatidylcholine, dioleylphosphatidylcholine, dipalmitoylphosphatidylcholine, disteroylphosphatidylcholine, behenoylphosphatidylcholine, arachidoylphosphatidylcholine and combinations thereof.14. The system of claim 9 wherein the mean aerodynamic diameter of the perforated microstructures is between 0.5 and 5 μm.15. The system of claim 9 wherein said bioactive agent is selected from the group consisting of antiallergics, bronchodilators, pulmonary lung surfactants, analgesics, antibiotics, antiinfectives, leukotriene inhibitors or antagonists, antihistamine, antiinflammatories, antineoplastics, antocholinergics, anesthetics, anti-tuberculars, imaging agents, cardiovascular agents, enzyme, steroids, genetic material, viral vectors, antisense agents, proteins, peptides and combinations thereof.16. The system of claim 9 wherein said bioactive agent comprises a compound selected from the group consisting of proteins, peptides and genetic material.17. The system of claim 9 wherein said fluid reservoir is a multi-dose reservoir or a single dose reservoir.18. The system of claim 9 wherein said nebulizer is a jet nebulizer, an ultrasonic nebulizer or a single-bolus nebulizer.19. The system of claim 9 wherein the respiratory dispersion comprises a creaming time of greater than 1 minute.20. The system of claim 9 wherein the respiratory dispersion comprises a creaming time of greater than 30 minutes.21. The system of claim 9 wherein the perforated microstructures comprise a geometric diameter of 1-30 μm.22. The system of claim 15 wherein the bioactive agent is an antiinfective selected from the group consisting of cephalosporines, macrolides, quinoline, penicillins, streptomycin, sulphonamides, tetracyclines, and pentamidine.
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이 특허에 인용된 특허 (110)
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