# US 2019/0167580 A1 · Delivery of Active Agents > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2019/0167580 A1 - Document ID: US20190167580A1 - Status: Published application - Kind: A1 - Application number: 16/267,231 - Filed: 2019-02-04 - Published: 2019-06-06 - Earliest claimed: 2007-10-24 - Assignees: MannKind Corporation - Applicants: MannKind Corporation - Inventors: Peter Richardson; Robert A. Baughman; Andrea Leone-Bay; Donald Costello - Web page: https://patentgrep.com/patent/US20190167580A1 ## CPC - A61K 9/0075: {for inhalation via a dry powder inhaler [DPI], e.g. comprising micronized drug mixed with lactose carrier particles} - A61K 9/1617: {Organic compounds, e.g. phospholipids, fats} - A61K 9/1688: {resulting in pure drug agglomerate optionally containing up to 5% of excipient} - A61K 31/495: 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}) - A61K 38/26: Glucagons - A61P 3/00: Drugs for disorders of the metabolism (of the blood or the extracellular fluid A61P7/00) - A61P 3/04: Anorexiants; Antiobesity agents - A61P 3/10: for hyperglycaemia, e.g. antidiabetics - A61P 5/00: Drugs for disorders of the endocrine system - A61P 5/02: of the hypothalamic hormones, e.g. TRH, GnRH, CRH, GRH, somatostatin - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS ## 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. ## Claims ### Claim 1 A method of administering a labile active agent to a patient comprising: administering to said patient in need thereof an effective amount of a pharmaceutical composition comprising a diketopiperazine and one or more active agents by pulmonary inhalation; wherein the one or more active agents is sensitive to enzymatic deactivation or degradation when in contact with local peripheral and vascular tissue, and said pharmaceutical composition provides avoidance of enzymatic deactivation or degradation of the one or more active agents. ### Claim 2 (depends on 1) The method of claim 1, wherein said diketopiperazine is 2,5-diketo-3,6-di(4-X-aminobutyl)piperazine; wherein X is selected from the group consisting of succinyl, glutaryl, maleyl, and fumaryl; or a pharmaceutically acceptable salt thereof. ### Claim 3 (depends on 1) The method of claim 1, wherein the pharmaceutical composition is a dry powder formulation. ### Claim 4 (depends on 3) The method of claim 3, wherein said dry powder formulation further comprises a pharmaceutically acceptable carrier or excipient. ### Claim 5 (depends on 3) The method of claim 3, wherein the dry powder formulation is administered using a dry powder inhalation system. ### Claim 6 (depends on 1) The method of claim 1, wherein the at least one of the one or more active agents is a vasoactive agent. ### Claim 7 (depends on 6) The method of claim 6, wherein the vasoactive agent is a prostaglandin. ### Claim 8 (depends on 7) The method of claim 7, wherein the prostaglandin is PG 12. ### Claim 9 (depends on 6) The method of claim 6, wherein the at least one vasoactive agent is administered at dosages ranging from about 0.01 mg to about 3 mg. ### Claim 10 (depends on 1) The method of claim 1, wherein said patient is in need of treatment with a vasodilator. ### Claim 11 (depends on 1) The method of claim 1, wherein the step of administering said pharmaceutical composition to said patient comprises administering said pharmaceutical composition using a breath-powered dry powder inhaler comprising a cartridge. ### Claim 12 A method of improving the effectiveness of a labile active agent in a patient comprising: administering by inhalation a pharmaceutical composition comprising a diketopiperazine microparticle and one or more active agents, wherein about 35% to about 75% of the microparticles have an aerodynamic diameter of less than 5.8 μm; wherein the labile active agent when administered by injection is subject to degradation in the patient as a result of exposure to peripheral tissue, vascular venous tissue, or liver metabolism, and said labile active agent effectiveness is reduced by said degradation prior to reaching a site of action. ### Claim 13 (depends on 12) The method of claim 12, wherein said diketopiperazine is 2,5-diketo-3,6-di(4-X-aminobutyl)piperazine; wherein X is selected from the group consisting of succinyl, glutaryl, maleyl, and fumaryl; or a pharmaceutically acceptable salt thereof. ### Claim 14 (depends on 12) The method of claim 12, wherein the pharmaceutical composition is a dry powder formulation. ### Claim 15 (depends on 12) The method of claim 12, wherein said labile active agent is a prostaglandin. ### Claim 16 (depends on 15) The method of claim 15, wherein the prostaglandin is PG 12. ### Claim 17 A method of administering a prostaglandin to a patient in need thereof comprising: administering to said patient an inhalable dry powder pharmaceutical composition comprising diketopiperazine microparticles and said prostaglandin, wherein about 35% to about 75% of the diketopiperazine microparticles have an aerodynamic diameter of less than 5.8 μm, wherein the prostaglandin is subject to degradation in a patient as a result of exposure to peripheral tissue, vascular venous tissue, or liver metabolism when administered by other routes of administration. ### Claim 18 (depends on 17) The method of claim 17, wherein the inhalable dry powder further comprises an additional vasoactive agent. ### Claim 19 (depends on 17) The method of claim 17, wherein the diketopiperazine microparticles comprise 2,5-diketo-3,6-di(4-X-aminobutyl)piperazine and X is fumaryl. ### Claim 20 A method of treating pulmonary disease to a patient in need thereof comprising: administering to said patient an inhalable dry powder formulation comprising a therapeutically effective amount of a prostaglandin using a breath-powered dry powder inhaler, wherein said formulation comprises from about 0.01 mg to about 3 mg of said prostaglandin. ### Claim 21 (depends on 20) The method of claim 20, wherein said prostaglandin is PG I2.