Delivery of beta-blockers through an inhalation route

• US 20030005924A1
• Filed: 05/20/2002
• Published: 01/09/2003
• Est. Priority Date: 05/24/2001
• Status: Active Grant

• Current Assignee: Alexza Pharmaceuticals Inc. (Grupo Ferrer Internacional SA)
• Original Assignee: Alexza Molecular Delivery Corporation (Grupo Ferrer Internacional SA)
• Inventors: Zaffaroni, Alejandro C., Rabinowitz, Joshua D.
• Granted Patent: US 6,740,307 B2
• Time in Patent Office: Days
• US Class Current: 128/200.14
• CPC Class Codes: A61K 31/00 Medicinal preparations containing organic active ingredients
• CPC Class Codes: A61K 31/137 Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
• CPC Class Codes: A61K 31/138 Aryloxyalkylamines, e.g. propranolol, tamoxifen, phenoxybenzamine atenolol A61K31/165; pindolol A61K31/404; timolol A61K31/5377
• CPC Class Codes: A61K 31/165 having aromatic rings, e.g. colchicine, atenolol, progabide
• CPC Class Codes: A61K 31/19 Carboxylic acids, e.g. valproic acid salicylic acid A61K31/60
• CPC Class Codes: A61K 31/192 having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid cannabinoids A61K31/658
• CPC Class Codes: A61K 31/195 having an amino group
• CPC Class Codes: A61K 31/216 of acids having aromatic rings, e.g. benactizyne, clofibrate
• CPC Class Codes: A61K 31/27 of carbamic or thiocarbamic acids, meprobamate, carbachol, neostigmine
• CPC Class Codes: A61K 31/404 Indoles, e.g. pindolol
• CPC Class Codes: A61K 31/405 Indole-alkanecarboxylic acids; Derivatives thereof, e.g. tryptophan, indomethacin
• CPC Class Codes: A61K 31/407 condensed with other heterocyclic ring systems, e.g. ketorolac, physostigmine
• CPC Class Codes: A61K 31/4196 1,2,4-Triazoles
• CPC Class Codes: A61K 31/421 1,3-Oxazoles, e.g. pemoline, trimethadione
• CPC Class Codes: A61K 31/422 not condensed and containing further heterocyclic rings
• CPC Class Codes: A61K 31/423 condensed with carbocyclic rings
• CPC Class Codes: A61K 31/437 the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
• CPC Class Codes: A61K 31/473 ortho- or peri-condensed with carbocyclic ring systems, e.g. acridines, phenanthridines
• CPC Class Codes: A61K 31/485 Morphinan derivatives, e.g. morphine, codeine
• CPC Class Codes: A61K 31/49 Cinchonan derivatives, e.g. quinine
• CPC Class Codes: A61K 31/495 : having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazinesA61K31/48 takes precedence ; with three nitrogen atoms A61K31/53
• CPC Class Codes: A61K 31/496 : Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
• CPC Class Codes: A61K 31/4985 : Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
• CPC Class Codes: A61K 31/501 : not condensed and containing further heterocyclic rings
• CPC Class Codes: A61K 31/519 : ortho- or peri-condensed with heterocyclic rings
• CPC Class Codes: A61K 31/53 : having six-membered rings with three nitrogens as the only ring hetero atoms, e.g. chlorazanil, melamine melarsoprol A61K31/555 ; with four nitrogen atoms A61K31/495
• CPC Class Codes: A61K 31/551 : having two nitrogen atoms, e.g. dilazep
• CPC Class Codes: A61K 31/5517 : condensed with five-membered rings having nitrogen as a ring hetero atom, e.g. imidazobenzodiazepines, triazolam
• CPC Class Codes: A61K 47/54 : the modifying agent being an organic compound
• 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: A61K 9/12 : Aerosols; Foams A61K9/0043, A61K9/0056, A61K9/006, A61K9/0073 take precedence; spray-films A61K9/7015
• CPC Class Codes: A61M 11/042 : electrical
• CPC Class Codes: A61M 15/06 : Inhaling appliances shaped like cigars, cigarettes or pipes
• CPC Class Codes: A61M 2205/8206 : battery-operated
• CPC Class Codes: A61P 15/10 : for impotence
• CPC Class Codes: A61P 21/02 : Muscle relaxants, e.g. for tetanus or cramps
• CPC Class Codes: A61P 25/00 : Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/06 : Antimigraine agents
• CPC Class Codes: A61P 25/08 : Antiepileptics; Anticonvulsants
• CPC Class Codes: A61P 25/16 : Anti-Parkinson drugs
• CPC Class Codes: A61P 25/18 : Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
• CPC Class Codes: A61P 25/20 : Hypnotics; Sedatives
• CPC Class Codes: A61P 25/22 : Anxiolytics
• CPC Class Codes: A61P 25/24 : Antidepressants
• CPC Class Codes: A61P 25/32 : Alcohol-abuse
• CPC Class Codes: A61P 29/00 : Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 31/04 : Antibacterial agents
• CPC Class Codes: A61P 37/08 : Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: F24V 30/00 : Apparatus or devices using heat produced by exothermal chemical reactions other than combustion

Abstract

The present invention relates to the delivery of beta-blockers through an inhalation route. Specifically, it relates to aerosols containing atenolol, pindolol, esmolol, propranolol, or metoprolol that are used in inhalation therapy. In a composition aspect of the present invention, the aerosol comprises particles comprising at least 5 percent by weight of atenolol, pindolol, esmolol, propranolol, or metoprolol. In a method aspect of the present invention, one of atenolol, pindolol, esmolol, propranolol, or metoprolol is delivered to a mammal through an inhalation route. The method comprises: a) heating a composition, wherein the composition comprises at least 5 percent by weight of atenolol, pindolol, esmolol, propranolol, or metoprolol, to form a vapor; and, b) allowing the vapor to cool, thereby forming a condensation aerosol comprising particles, which is inhaled by the mammal. In a kit aspect of the present invention, a kit for delivering atenolol, pindolol, esmolol, propranolol, or metoprolol through an inhalation route to a mammal is provided which comprises: a) a composition comprising at least 5 percent by weight of atenolol, pindolol, esmolol, propranolol, or metoprolol; and, b) a device that forms a atenolol, pindolol, esmolol, propranolol, or metoprolol containing aerosol from the composition, for inhalation by the mammal.

Claims

1. An aerosol for inhalation therapy, wherein the aerosol comprises particles comprising at least 10 percent by weight of atenolol, pindolol, esmolol, propranolol, or metoprolol.

2. The aerosol according to claim 1, wherein the aerosol particles have a mass median aerodynamic diameter of less than 3 microns.

3. The aerosol according to claim 1, wherein the particles comprise less than 5 percent by weight of atenolol, pindolol, esmolol, propranolol, or metoprolol degradation products.

4. The aerosol according to claim 1, wherein the aerosol comprises particles comprising at least 90 percent by weight of ephedrine or atenolol, pindolol, esmolol, propranolol, or metoprolol.

5. The aerosol according to claim 4, wherein the aerosol comprises particles comprising at least 95 percent by weight of atenolol, pindolol, esmolol, propranolol, or metoprolol.

6. A method of delivering atenolol, pindolol, esmolol, propranolol, or metoprolol to a mammal through an inhalation route, wherein the route comprises:

a) heating a composition, wherein the composition comprises at least 5 percent by weight of atenolol, pindolol, esmolol, propranolol, or metoprolol, to form a vapor; and

,

b) allowing the vapor to cool, thereby forming a condensation aerosol comprising particles,

which is inhaled by the mammal.

7. The method according to claim 6, wherein the particles comprise at least 10 percent by weight of atenolol, pindolol, esmolol, propranolol, or metoprolol.

8. The method according to claim 6, wherein the aerosol particles have a mass median aerodynamic diameter of less than 3 microns.

9. The method according to claim 6, wherein the particles comprise less than 5 percent by weight of atenolol, pindolol, esmolol, propranolol, or metoprolol degradation products.

10. The method according to claim 8, wherein the aerosol comprises particles comprising at least 90 percent by weight of atenolol, pindolol, esmolol, propranolol, or metoprolol.

11. The method according to claim 10, wherein the aerosol comprises particles comprising at least 95 percent by weight of atenolol, pindolol, esmolol, propranolol, or metoprolol.

12. A kit for delivering atenolol, pindolol, esmolol, propranolol, or metoprolol through an inhalation route to a mammal, wherein the kit comprises:

a ) a composition comprising at least 5 percent by weight of atenolol, pindolol, esmolol, propranolol, or metoprolol; and

,

b) a device that forms a atenolol, pindolol, esmolol, propranolol, or metoprolol aerosol from the composition, for inhalation by the mammal and wherein the device comprises;

a) an element for heating the atenolol, pindolol, esmolol, propranolol, or metoprolol

composition to form a vapor;

b) an element allowing the vapor to cool to form an aerosol; and

,

c) an element permitting the mammal to inhale the aerosol.