Delivery of active agents

Patent metadata

Field	Value
Publication number	US-2024197627-A1
Application number	US-202418434301-A
Country	US
Kind code	A1
Filing date	Feb 6, 2024
Priority date	Oct 24, 2007
Publication date	Jun 20, 2024
Grant date	—

Abstract

A method of introducing a physiologically-active agent into the circulatory system of a mammal is disclosed herein. The method utilizes a rapid drug delivery system which prevents deactivation or degradation of the active agent being administered to a patient in need of treatment. In particular, the drug delivery system is designed for pulmonary drug delivery such as by inhalation, for delivery of the active agents such as proteins and peptides to the pulmonary circulation in a therapeutically effective manner avoiding degradation of the active agents in peripheral and vascular tissue before reaching the target site.

First claim

We claim:

1 ) A drug delivery system for oral inhalation comprising a dry powder inhaler and a single dose cartridge comprising an inhalable dry powder formulation comprising precipitated microparticles comprising assemblages of crystalline plates having irregular surfaces of 2,5-diketo-3,6-di(4-X-aminobutyl)piperazine and internal voids, and an active agent prone to rapid degradation as a result of exposure to peripheral tissue, vascular venous tissue, or liver metabolism entrapped within the microparticles, said inhalable dry powder provided in a dose 0.01 mg to 3 mg in said single dose cartridge, wherein 35% to 75% of the microparticles of the dry powder formulation that are delivered to the pulmonary alveoli have an aerodynamic diameter of less than 5.8 um, and wherein said active agent comprises a prostaglandin, and further wherein said active agent prone to rapid degradation as a result of exposure to peripheral tissue, vascular venous tissue, or liver metabolism is not an antibody or insulin.

2 ) The drug delivery system of claim 1 , wherein the dry powder formulation further comprises a sugar. The drug delivery system of claim 13 , wherein the prostaglandin is PG I2.

3 ) The drug delivery system of claim 1 , wherein X is selected from the group consisting of succinyl, glutaryl, maleyl and fumaryl; or a pharmaceutically acceptable salt thereof.

4 ) A drug delivery system for inhalation and treating a disease or disorder in a patient comprising a dry powder inhaler and a single dose cartridge comprising an inhalable dry powder formulation comprising precipitated microparticles comprising assemblages of crystalline plates having irregular surfaces of 2,5-diketo-3,6-di(4-X-aminobutyl)piperazine and internal voids, and an active agent prone to rapid degradation as a result of exposure to peripheral tissue, vascular venous tissue, or liver metabolism entrapped within the microparticles, said prostaglandin provided in a dose of 0.01 mg to 3 mg in said single dose cartridge, wherein the microparticles that are delivered to the pulmonary alveoli have an aerodynamic diameter of less than 5.8 um, and wherein said active agent comprises a prostaglandin, and further wherein said active agent prone to rapid degradation as a result of exposure to peripheral tissue, vascular venous tissue, or liver metabolism is not an antibody or insulin.

5 ) The drug delivery system of claim 3 , wherein X is selected from the group consisting of succinyl, glutaryl, maleyl and fumaryl; or a pharmaceutically acceptable salt thereof.

6 ) The drug delivery system of claim 4 , wherein X is selected from the group consisting of succinyl, glutaryl, maleyl and fumaryl; or a pharmaceutically acceptable salt thereof.

7 ) The drug delivery system of claim 5 , wherein X is fumaryl; or a pharmaceutically acceptable salt thereof.

8 ) The drug delivery system of claim 6 , wherein X is fumaryl; or a pharmaceutically acceptable salt thereof.

9 ) The drug delivery system of claim 1 , wherein the prostaglandin is PG I2.

10 ) The drug delivery system of claim 1 , wherein said precipitation comprises pH controlled precipitation of a 2,5-diketo-3,6-di(4-X-aminobutyl)piperazine acid.

11 ) The drug delivery system of claim 4 , wherein said precipitation comprises pH controlled precipitation of a 2,5-diketo-3,6-di(4-X-aminobutyl)piperazine acid.

12 ) A method of treating a disease or disorder in a patient in need thereof comprising providing the drug delivery system of claim 1 and administering to said patient the inhalable dry powder by oral inhalation.

Assignees

• Mannkind Corp

Inventors

• Richardson Peter
• Baughman Robert A
• Leone-Bay Andrea
• Costello Donald

Classifications

• A61K38/26

  Glucagons · CPC title

• A61K31/495

  having six-membered rings with two {or more} nitrogen atoms as the only ring heteroatoms, e.g. piperazine {or tetrazines}(A61K31/48 takes precedence {; with three nitrogen atoms A61K31/53}) · CPC title

• A61K9/1688

  resulting in pure drug agglomerate optionally containing up to 5% of excipient · CPC title

• A61K9/1617

  Organic compounds, e.g. phospholipids, fats · CPC title

• A61K31/496

  Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin · CPC title