Inhalation nebulizer

• US 6,962,151 B1
• Filed: 10/27/2000
• Issued: 11/08/2005
• Est. Priority Date: 11/05/1999
• Status: Expired due to Term

• Current Assignee: PARI Pharma GmbH (PARI MEDICAL HOLDING GmbH)
• Original Assignee: Pari GmbH Spezialisten Fur Effektive Inhalation (PARI MEDICAL HOLDING GmbH)
• Inventors: Gallem, Thomas, Stangl, Roland, Urich, Markus, Keller, Manfred, Knoch, Martin, Liening-Ewert, Rainer
• Primary Examiner(s): PATEL, MITAL B
• Application Number:
  US10/129,498
• Time in Patent Office: 1,838 Days
• Field of Search: 128/200.14, 128/200.16, 128/200.23, 128/200.17, 128/200.18, 128/200.22, 239/338, 239/102.2
• US Class Current: 128/200.14
• CPC Class Codes: A61M 15/0015 located upstream of the dispenser, i.e. not traversed by the product
• CPC Class Codes: A61M 15/0018 with exhalation check valves
• CPC Class Codes: A61M 15/0085 using ultrasonics spraying or atomising liquids using ultrasonic vibrations in general B05B17/06
• CPC Class Codes: B05B 17/0646 Vibrating plates, i.e. plates being directly subjected to the vibrations, e.g. having a piezoelectric transducer attached thereto

Abstract

An inhalation nebulizer (1) includes an aerosol generator (2) that has a diaphragm (22) vibrated by a vibration generator (23). The inhalation nebulizer (1) includes a liquid storage container (21) that is in fluid contact with the diaphragm (22). A liquid contained in the storage container (21) is atomized into a mixing chamber (3) through openings in the diaphragm and can subsequently be inhaled by a patient.

Claims

1. An inhalation nebulizer comprising:

an aerosol generator comprising;

a liquid storage container into which a liquid medicament or a medicament-containing liquid can be filled;

a diaphragm having a first side and an opposite second side, the diaphragm having a plurality of openings extending therethrough from the first side to the second side, where the first side is connected to the liquid storage container such that a liquid filled into the liquid storage container comes into contact with the first side of the diaphragm; and

a vibration generator capable of vibrating the diaphragm so that a liquid filled into the liquid storage container is atomized on the second side of the diaphragm through the openings of the diaphragm;

a mixing chamber into which the aerosol generator expels the aerosol, the mixing chamber in contact with the second side of the diaphragm;

an inhalation valve that is open to allow an inflow of ambient air into the mixing chamber during an inhalation phase and is closed to prevent escape of the aerosol from the mixing chamber during an exhalation phase; and

an exhalation valve that is open to allow the discharge of the respiratory air of a patient into the surroundings during the exhalation phase and is closed to prevent the inflow of ambient air during the inhalation phase.

2. The inhalation nebulizer of claim 1, wherein the liquid storage container comprises a single dose container containing a single pre-metered medicament volume.

3. The inhalation nebulizer of claim 1, wherein the liquid storage container comprises a multi dose container containing a plurality of pre-metered medicament volumes.

4. The inhalation nebulizer of claim 1, wherein the liquid storage container comprises a liquid reservoir that is directly fitted into the inhalation nebulizer as a container closure system.

5. The inhalation nebulizer of claim 1, wherein the aerosol produced by the inhalation nebulizer has a mass median aerodynamic diameter between about 1 μ

m to about 30 μ

m.

6. The inhalation nebulizer of claim 1, wherein the diaphragm forms a part of the wall of the liquid storage container and partially defines the liquid storage container such that a liquid filled into the liquid storage container directly contacts the diaphragm.

7. The inhalation nebulizer of claim 1, wherein the exhalation valve is arranged at a mouthpiece which is removably mounted at the mixing chamber and through which the patient inhales the aerosol from the mixing chamber.

8. The inhalation nebulizer of claim 1, wherein the exhalation valve is arranged in a wall of the mixing chamber.

9. The inhalation nebulizer of claim 1, wherein the inhalation valve is located on the same side of the diaphragm as the liquid storage container.

48. The inhalation nebulizer of claim 9, further comprising an annular gap surrounding the liquid storage container, such that ambient air passes through the annular gap before reaching the mixing chamber.

10. An inhalation nebulizer comprising:

an aerosol generator comprising;

a liquid storage container into which a liquid medicament or a medicament-containing liquid can be filled;

a diaphragm which on one side is connected to the liquid storage container such that a liquid filled into the liquid storage container comes into contact with the one side of the diaphragm; and

a vibration generator capable of vibrating the diaphragm so that a liquid filled into the liquid storage container is atomized on the other side of the diaphragm through the openings of the diaphragm;

a mixing chamber into which the aerosol generator expels the aerosol;

an inhalation valve that is open to allow an inflow of ambient air into the mixing chamber during an inhalation phase and is closed to prevent escape of the aerosol from the mixing chamber during an exhalation phase; and

an exhalation valve that is open to allow the discharge of the respiratory air of a patient into the surroundings during the exhalation phase and is closed to prevent the inflow of ambient air during the inhalation phase,

wherein the liquid storage container is a rotationally symmetrical body, the diaphragm arranged at a front side of the rotationally symmetrical body or cylinder is a circular disk, and the vibration generator is a circular ring surrounding the diaphragm.

11. The inhalation nebulizer of claim 10, wherein the mixing chamber is rotationally symmetrical, and the aerosol diaphragm generator comprises a circular ring disk which is arranged circumferentially at the liquid storage container and which rests upon a projection provided in a cylindrical section of the mixing chamber.

12. The inhalation nebulizer of claim 11, wherein a cap closes the rotationally symmetrical section of the mixing chamber and fixes in position a flexible valve element of the inhalation valve.

13. The inhalation nebulizer of claim 11, wherein the mixing chamber has a cylindrical section.

14. The inhalation nebulizer of claim 10, wherein the diaphragm is arranged perpendicular to the axis of rotation of the rotationally symmetrical section of the mixing chamber.

15. The inhalation nebulizer of claim 10, wherein the diaphragm is arranged inclined to the axis of rotation of the rotationally symmetrical section of the mixing chamber.

16. The inhalation nebulizer of claim 10, wherein the liquid storage container comprises a cylinder.

17. An inhalation nebulizer comprising;

an aerosol generator comprising;

a liquid storage container into which a liquid active agent or a liquid containing an active agent is filled as one of a solution, a suspension and an emulsion;

a diaphragm having a first side and an opposite second side, the diaphragm having a plurality of openings extending therethrough from the first side to the second side, where the first side is connected to the liquid storage container such that a liquid filled into the liquid storage container comes into contact with the first side of the diaphragm; and

a vibration generator capable of vibrating the diaphragm so that a liquid filled into the liquid storage container is atomized on the second side of the diaphragm through the openings of the diaphragm;

a mixing chamber into which the aerosol generator expels the aerosol, the mixing chamber in contact with the second side of the diaphragm;

an inhalation valve that is open to allow an inflow of ambient air into the mixing chamber during an inhalation phase and is closed to prevent escape of the aerosol from the mixing chamber during an exhalation phase; and

an exhalation valve that is open to allow the discharge of the respiratory air of a patient into the surroundings during the exhalation phase and is closed to prevent the inflow of ambient air during the inhalation phase.

18. The inhalation nebulizer of claim 17, wherein the active agent is provided as a submicron suspension.

19. The inhalation nebulizer of claim 17, wherein the active agent is provided as one of a liposome, a nanosome, a microcapsule or a nanocapsule.

20. The inhalation nebulizer of claim 17, wherein the active agent comprises a drug effective against a disease selected from the group of diseases consisting of asthma, chronic obstructive pulmonary disease, lung infections, cystic fibrosis, allergies, pain, migraine, rheumatism, epilepsy, sleeplessness, cancer, diabetes, immune and hormone disorders and gene defects.

21. The inhalation nebulizer of claim 17, wherein the active agent comprises a drug that cannot be administered orally.

22. The inhalation nebulizer of claim 17, wherein the active agent comprises a drug or a combination of drugs for topical or systemic delivery via either a nasal or a pulmonary route.

23. The inhalation nebulizer of claim 17, wherein the active agent comprises an anti-asthmatic.

24. The inhalation nebulizer of claim 17, wherein the active agent comprises an anti-inflammatory drug.

25. The inhalation nebulizer of claim 17, wherein the active agent comprises an antibiotic or an anti-infectiva.

26. The inhalation nebulizer of claim 17, wherein the active agent comprises an anti-tuberculotic.

27. The inhalation nebulizer of claim 17, wherein the active agent is selected from the group of active agents consisting of an anti-epileptic drug, an anti-convulsive drug, an anti-emetic, a pain killer, an anti-rheumatic, an anti-cancer drug, a mucolytic drug, a sleeping assistant, an anti-mycotic, a sexual stimulant, a protein or peptide, heparane and a gene.

28. The inhalation nebulizer of claim 17, wherein the active agent is selected from the group of active agents consisting of an anti-diabetic drug, insulin and a hormone.

29. The inhalation nebulizer of claim 17, wherein the active agent comprises a beta-agonist or an anti-cholinergic.

30. The inhalation nebulizer of claim 17, wherein the active agent is selected from the group of active agents consisting of a corticosteroid, a leukotriene antagonist, a bradykinin antagonist, a cromone, an anti-histamine and an antibody.

31. The inhalation nebulizer of claim 17, wherein the active agent is selected from the group of active agents consisting of an aminoglycoside, a cephalosporine, a macrolide, a chinolone, a nitroimidazol, a glycopeptide, a polyenantibiotic, a beta-lactam, a tetracycline, a quinolone, a sulfonamide, and an azol derivative.

32. The inhalation nebulizer of claim 17, wherein the active agent is selected from the group of active agents consisting of a benzodiazepine, a barbitute and a succinimide.

33. The inhalation nebulizer of claim 17, wherein the active agent comprises sildenafil.

34. The inhalation nebulizer of claim 17, wherein the active agent is selected from the group of active agents consisting of alpha anti-trypsine, erythropoetine, interferones, kinases, elastases, peptides and proteines, which active agents can be administered advantageously via a nasal or pulmonary route.

35. The inhalation nebulizer of claim 17, wherein the active agent is selected from the group of active agents consisting of salbutamol, levalbuterol formoterol, fenoterol, salmeterol, bambuterol, brocaterol, clenbuterol, terbutalin, tolubuterol, epinephrin, isoprenalin, and hexaprenalin.

36. The inhalation nebulizer of claim 17, wherein the active agent is selected from the group of active agents consisting of tiotropium, oxitropium, ipratropium, and glycopyrrolate.

37. The inhalation nebulizer of claim 17, wherein the active agent is selected from the group of active agents consisting of acetylcystein, ambroxol, carbocystein, tyloxapol, dipalmytoylphosphatidylcholin, recombinant surfactant proteins, and D-Nase.

38. The inhalation nebulizer of claim 17, wherein the active agent is selected from the group of active agents consisting of romoglycate, nedocromil, beclomethasone, betamethasone, budesonide, ciclesonide, flunisolide, fluticasone, icomethasone, mometasone, rofleponide, triamcinolone, bradykinine-, prostaglandine-, leucotriene- and platelet activating factor antagonists.

39. The inhalation nebulizer of claim 17, wherein the active agent is selected from the group of active agents consisting of amoxycillin, piperacillin, clavulan acid, sulbactam, ceflaclor, cefazedon, Cefuroxim, Cefoxitin, cefodizim, cefsulodin, cefpodixim, cefixim, imipenem, cilastatin, aztrenonam, streptomycin neomycin, paromomycin, kanamycin, gentamycin, amicacin, tobramycin, spectinomycine, doxycyclin, minocycline, erhytromycine, clarithromycine, roxithromycine, azithromycine, josamycine, spiramycine, Ciprofloxacin, Ofloxacine, Levofloxacine, pefloxacine, lomefloxacine, fleroxacine, clinafloxacine, sitafloxacine, gemifloxacine, balofloxacine, trovafloxacine, moxifloxacine, metronidazol, tinidazol, chloramphenicol, lincomycine, clindamycine, fosfomycine, Vancomycine and Teicoplanine.

40. The inhalation nebulizer of claim 17, wherein the active agent is selected from the group of active agents consisting of rifampicine, isoniacide, cycloserine, terizidone, and ansamycine.

41. The inhalation nebulizer of claim 17, wherein the active agent is selected from the group of active agents consisting of clotrimazol, oxiconazol, miconazol, ketoconazol, itraconazol, fluconazol, amphotericine B, natamycine, nystatine, flucytosine, and Pentamidine.

42. The inhalation nebulizer of claim 17, wherein the active agent is selected from the group of active agents consisting of dimepranol-4-acetate amideo benzoate, thymopentin, interferones, filgrastine, interleukine, azathioprine, and cyclosporine;

virustatics such as podophyllotoxine, vidarabine, tromantadine, zidovudine, and a-anti-trypsin.

43. The inhalation nebulizer of claim 17, wherein the active agent is selected from the group of active agents consisting of corticotropine, tetracosactide, choriogonandotropine, urofolitropine, urogonadotropine, saomatotropine, metergoline, desmopressine, oxytocine, argipressine, ornipressine, leuproreline, triptoreline, gonadoreline, busereline, nafareline, goselerine, somatostatine, parathyroide gland hormones, Dihydrotachysterole, calcitonine, clodron acid, etidron acid, thyroid gland therapeutics, anabolics, androgens, estrogens, gestagenes, and antiestrogenes.

44. The inhalation nebulizer of claim 17, wherein the active agent is selected from the group of active agents consisting of nimustine, melphanlane, carmustine, lomustine, cyclophosphosphamide, ifosfamide, trofosfamide, chlorambucil, busulfane, treosulfane, prednimustine, thiotepa, cytarabine, fluorouracil, methotrexate, mercaptopurine, tioguanine, vinblastine, vincristine, vindesine, alcarubicine, bleomycine, dactinomycine, daunorubicine, doxorubicine, epirubicine, idarubicine, mitromycine, plicamycine, carboplatinum, cis-platinum, titanocendichloride Amsacrine, dacarbazine, estramustine, etoposide, hydroxycarbamide, mitoxanthrone, procarbazine, and temiposide.

45. The inhalation nebulizer of claim 17, wherein the active agent is selected from the group of active agents consisting of Proxibarbal, lisuride, methysergide, dihydroergotamine, ergotamine, clonidine, pizotifene, benzodiazepines, barbiturates, cyclopyrrolones, imidazopyridines, arbiturates, Pheytoin, Primidone, mesuximide, ethosuximide, sultiam, carbamazepin, valproic acid, vigabatrine, Levodopa, carbidopa, benserazide, selegiline, bromocriptine, amantadine, tiapride, Thiethylperazine, bromopride, domperidone, granisetrone, ondoasetrone, tropisetrone, pyridoxine, morphine, codeine, hydromorphone, methadone, fenpipramide, fentanyl, piritramide, pentazocine, buprenorphine, nalbuphine, tilidine, N-methylated barbiturates, thiobarbiturates, ketamine, etomidate, propofol, benzodiazepines, droperidol, haloperidol, alfentanyl, sulfentanyl, tumor necrosis factor alpha and non steroidal anti-inflammatory drugs.

46. The inhalation nebulizer of claim 17, wherein the active agent is selected from the group of active agents consisting of insulin, sulfonylurea derivatives, biguanids, glitizols, glucagon, diazoxid, interleukines, interferones, tumor necrosisfactor (TNF), and colony stimulating factors.

47. The inhalation nebulizer of claim 17, wherein the active agent is selected from the group of active agents consisting of proteins, peptides, heparine, heparinoids, urokinases, streptokinases, ATP-ase, prostacycline, sexual stimulants, and genes, which active agents cannot be administered orally can be delivered advantageously by the inhalation nebulizer either by the nasal or pulmonary route.