Aerosol generating method and device

• US 9,308,208 B2
• Filed: 07/30/2010
• Issued: 04/12/2016
• Est. Priority Date: 06/05/2001
• Status: Expired due to Term

• Current Assignee: Alexza Pharmaceuticals Inc. (Grupo Ferrer Internacional SA)
• Original Assignee: Alexza Pharmaceuticals Inc. (Grupo Ferrer Internacional SA)
• Inventors: Wensley, Martin J., Mufson, Daniel, Hodges, Craig C., Lloyd, Peter M., Rogers, Daniel D.
• Primary Examiner(s): Haghighatian, Mina
• Application Number:
  US12/847,584
• Publication Number:
  US 20100294268A1
• Time in Patent Office: 2,083 Days
• US Class Current: 1/1
• CPC Class Codes: A61K 31/235 having an aromatic ring attached to a carboxyl group
• CPC Class Codes: A61K 31/4468 having a nitrogen directly attached in position 4, e.g. clebopride, fentanyl
• CPC Class Codes: A61K 31/485 Morphinan derivatives, e.g. morphine, codeine
• CPC Class Codes: A61K 31/519 ortho- or peri-condensed with heterocyclic rings
• CPC Class Codes: A61K 9/007 Pulmonary tract; Aromatherapy
• CPC Class Codes: A61K 9/0073 Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy; nasal sprays A61K9/0043; inhalation of vapours of volatile or heated drugs, e.g. essential oils or nicotine, A61K9/007; devices A61M
• CPC Class Codes: A61M 11/001 Particle size control
• CPC Class Codes: A61M 11/02 operated by air or other gas pressure applied to the liquid or other product to be sprayed or atomised sprayers for horticulture A01G, A01H; killing insects A01M; air humidifying by nozzles F24F6/14, F24F6/18; cooling by spraying F28B, F28C
• CPC Class Codes: A61M 11/044 with electrodes immersed in the liquid
• CPC Class Codes: A61M 15/00 Inhalators drug delivery in endotracheal tubes A61M16/04
• CPC Class Codes: A61M 15/0028 using prepacked dosages, one for each application, e.g. capsules to be perforated or broken-up
• CPC Class Codes: A61M 16/109 the humidifying liquid or the beneficial agent
• CPC Class Codes: A61M 2016/0039 in the inspiratory circuit
• CPC Class Codes: A61M 2205/3606 cooled
• CPC Class Codes: A61M 2205/3653 by Joule effect, i.e. electric resistance
• CPC Class Codes: A61M 2205/368 by electromagnetic radiation, e.g. IR waves
• CPC Class Codes: A61M 2205/50 with microprocessors or computers
• CPC Class Codes: A61P 23/00 Anaesthetics
• CPC Class Codes: B05B 17/04 operating with special methods
• CPC Class Codes: B05B 7/1686 involving vaporisation of the material to be sprayed or of an atomising-fluid-generating product

Abstract

A method and device are provided to generate an aerosol having a desired particle sizes, i.e., from molecular to about 10 microns, which can be used to effectively deliver a physiologically active compound to organs and tissues such as the lung, eye, mucosa and skin. The aerosol is formed through vaporization of the compound while mixing the resulting vapor with a gas, in a ratio, to form the desired particle size when a stable concentration of particles in the gas is reached.

Claims

1. A method for generating an aerosol comprising the steps of:

(a) depositing a coating comprising a physiologically active compound onto a substrate comprising dissolving the compound in an organic solvent, applying the solution to all or a portion of the substrate and allowing the solvent to evaporate;

(b) heating the physiologically active compound to vaporize at least a portion of the compound, following said evaporation;

(c) cooling the resulting vapor by mixing the vapor with a gas in a predetermined ratio, selected to form an aerosol comprised of particles within a desired size range when a stable concentration of particles in the gas is reached.

2. The method of claim 1 wherein the desired size range is a mass median aerodynamic diameter between about 1 to 3 microns.

3. The method of claim 1 wherein the desired size range is a mass median aerodynamic diameter between about 10 to 100 nanometers.

4. The method of claim 1 wherein the gas is air.

5. The method of claim 1 wherein the compound is selected from the group consisting of cannabinoid extracts from cannabis, THC, ketorolac, fentanyl, morphine, testosterone, ibuprofen, codeine, nicotine, Vitamin A, Vitamin E acetate, Vitamin E, nitroglycerin, pilocarpine, mescaline, testosterone enanthate, menthol, phencaramide, methsuximide, eptastigmine, promethazine, procaine, retinol, lidocaine, trimeprazine, isosorbide dinitrate, timolol, methyprylon, etamiphyllin, propoxyphene, salmetrol, vitamin E succinate, methadone, oxprenolol, isoproterenol bitartrate, etaqualone, Vitamin D3, ethambutol, ritodrine, omoconazole, cocaine, lomustine, ketamine, ketoprofen, cilazaprol, propranolol, sufentanil, metaproterenol, pentoxapylline, captopril, loxapine, cyproheptidine, carvediol, trihexylphenadine, alprostadil, melatonin, testosterone proprionate, valproic acid, acebutolol, terbutaline, diazepam, topiramate, pentobarbital, alfentanil HCl, papaverine, nicergoline, fluconazole, zafirlukast, testosterone acetate, droperidol, atenolol, metoclopramide, enalapril, albuterol, ketotifen, isoproterenol, amidarone HCl, zileuton, midazolam, oxycodone, cilostazol, propofol, nabilone, gabapentin, famotidine, lorezepam, naltrexone, acetaminophen, sumatriptan, bitolterol, nifedipine, phenobarbital, phentolamine, 13-cis retinoic acid, droprenilamine HCl, amlodipine, caffeine, zopiclone, tramadol HCl, pirbuterol, naloxone, meperidine HCl, trimethobenzamide, nalmefene, scopolamine, sildenafil, carbamazepine, procaterol HCl, methysergide, glutathione, olanzapine, zolpidem, levorphanol, buspirone and mixtures thereof.

6. The method of claim 1 wherein an inhalation dose of the compound is vaporized over a period of time no greater than 2 seconds.

7. The method of claim 1 wherein the mixing comprises passing the gas across the surface of the coating.

8. The method of claim 1 further comprising administering the resulting aerosol to a patient.

9. The method of claim 1 wherein the stable concentration is about 10⁹ particles/cc.

10. A method for generating an aerosol comprising the steps of:

(a) depositing a coating comprising a physiologically active compound onto a substrate comprising dissolving the compound in an organic solvent, applying the solution to all or a portion of the substrate and allowing the solvent to evaporate;

(b) heating a coating comprising a therapeutic amount of said physiologically active compound deposited onto said substrate to vaporize at least a portion of the compound, following said evaporation;

(c) cooling the resulting vapor by mixing the vapor with a gas in a predetermined ratio, selected to form an aerosol comprised of particles within a desired size range when a stable concentration of particles in the gas is reached.

11. The method of claim 10 wherein the desired size range is a mass median aerodynamic diameter between about 1 to 3 microns.

12. The method of claim 10 wherein the desired size range is a mass median aerodynamic diameter between about 10 to 100 nanometers.

13. The method of claim 10 wherein the gas is air.

14. The method of claim 10 wherein an inhalation dose of the compound is vaporized over a period of time no greater than 2 seconds.

15. The method of claim 10 wherein the mixing comprises passing the gas across the surface of the coating.

16. The method of claim 10 further comprising administering the resulting aerosol to a patient.

17. The method of claim 10 wherein the stable concentration is about 10⁹ particles/cc.

18. A method for generating an aerosol comprising the steps of:

(a) depositing a coating comprising a physiologically active compound onto a substrate comprising dissolving the compound in an organic solvent, applying the solution to all or a portion of the substrate and allowing the solvent to evaporate

(b) heating the physiologically active compound to vaporize at least a portion of the compound, following said evaporation;

(c) cooling the resulting vapor by mixing the vapor with a gas in a predetermined ratio, selected to form an aerosol comprised of particles within a desired size range that are sufficiently stable that they will remain within that range during the time necessary to administer the aerosol to a patient.

19. The method of claim 18 wherein the desired size range is a mass median aerodynamic diameter between about 1 to 3 microns.

20. The method of claim 18 wherein the desired size range is a mass median aerodynamic diameter between about 10 to 100 nanometers.

21. The method of claim 18 wherein the gas is air.

22. The method of claim 18 wherein the compound is selected from the group consisting of cannabinoid extracts from cannabis, THC, ketorolac, fentanyl, morphine, testosterone, ibuprofen, codeine, nicotine, Vitamin A, Vitamin E acetate, Vitamin E, nitroglycerin, pilocarpine, mescaline, testosterone enanthate, menthol, phencaramide, methsuximide, eptastigmine, promethazine, procaine, retinol, lidocaine, trimeprazine, isosorbide dinitrate, timolol, methyprylon, etamiphyllin, propoxyphene, salmetrol, vitamin E succinate, methadone, oxprenolol, isoproterenol bitartrate, etaqualone, Vitamin D3, ethambutol, ritodrine, omoconazole, cocaine, lomustine, ketamine, ketoprofen, cilazaprol, propranolol, sufentanil, metaproterenol, pentoxapylline, captopril, loxapine, cyproheptidine, carvediol, trihexylphenadine, alprostadil, melatonin, testosterone proprionate, valproic acid, acebutolol, terbutaline, diazepam, topiramate, pentobarbital, alfentanil HCl, papaverine, nicergoline, fluconazole, zafirlukast, testosterone acetate, droperidol, atenolol, metoclopramide, enalapril, albuterol, ketotifen, isoproterenol, amidarone HCl, zileuton, midazolam, oxycodone, cilostazol, propofol, nabilone, gabapentin, famotidine, lorezepam, naltrexone, acetaminophen, sumatriptan, bitolterol, nifedipine, phenobarbital, phentolamine, 13-cis retinoic acid, droprenilamine HCl, amlodipine, caffeine, zopiclone, tramadol HCl, pirbuterol, naloxone, meperidine HCl, trimethobenzamide, nalmefene, scopolamine, sildenafil, carbamazepine, procaterol HCl, methysergide, glutathione, olanzapine, zolpidem, levorphanol, buspirone and mixtures thereof.

23. The method of claim 18 wherein an inhalation dose of the compound is vaporized over a period of time no greater than 2 seconds.

24. The method of claim 18 wherein the mixing comprises passing the gas across the surface of the coating.

25. The method of claim 18 further comprising administering the resulting aerosol to a patient.

26. A method for generating an aerosol comprising the steps of:

(a) depositing a coating comprising a compound onto a substrate comprising dissolving the compound in an organic solvent, applying the solution to all or a portion of the substrate and allowing the solvent to evaporate;

(b) heating a coating comprising a therapeutic amount of a physiologically active compound deposited onto said substrate to vaporize at least a portion of the compound, following said evaporation;

(c) cooling the resulting vapor by mixing the vapor with a gas in a predetermined ratio, selected to form an aerosol comprised of particles within a desired size range that are sufficiently stable that they will remain within that range during the time necessary to administer the aerosol to a patient.

27. The method of claim 26 wherein the particle size is a mass median aerodynamic diameter between about 1 to 3 microns.

28. The method of claim 26 wherein the particle size is a mass median aerodynamic diameter between about 10 to 100 nanometers.

29. The method of claim 26 wherein the gas is air.

30. The method of claim 26 wherein an inhalation dose of the compound is vaporized over a period of time no greater than 2 seconds.

31. The method of claim 26 wherein the mixing comprises passing the gas across the surface of the coating.

32. The method of claim 26 further comprising administering the resulting aerosol to a patient.