Dry powder compositions of treprostinil prodrugs and methods of use thereof

Patent metadata

Field	Value
Publication number	US-2020338005-A1
Application number	US-202016860428-A
Country	US
Kind code	A1
Filing date	Apr 28, 2020
Priority date	Apr 29, 2019
Publication date	Oct 29, 2020
Grant date	—

Abstract

or an enantiomer, diastereomer, or a pharmaceutically acceptable salt thereof, (b) from about 0.01 wt % to about 3 wt % of DSPE-PEG2000, (c) from about 10 wt % to about 50 wt % of leucine, and the balance being (d) a sugar selected from the group consisting of trehalose and mannitol. The entirety of (a), (b), (c), and (d) is 100 wt %, and R1 is tetradecyl, pentadecyl, hexadecyl, heptadecyl, or octadecyl. The method includes administering an effective amount of the dry powder composition to the lungs of the patient by inhalation via a dry powder inhaler. In certain compositions and methods provided herein, R1 is hexadecyl, e.g., linear hexadecyl.

First claim

1 - 131 . (canceled)

132 . A dry powder composition comprising:
(a) from about 0.1 wt % to about 3 wt % of a compound of Formula (I):

or an enantiomer, diastereomer, or a pharmaceutically acceptable salt thereof, wherein R 1 is tetradecyl, pentadecyl, hexadecyl, heptadecyl, or octadecyl,
(b) from about 0.01 wt % to about 3 wt % of DSPE-PEG2000,
(c) from about 10 wt % to about 50 wt % of leucine, and
the balance being (d) a sugar selected from the group consisting of trehalose and mannitol,
wherein the entirety of (a), (b), (c), and (d) is 100 wt %.

133 . The dry powder composition of claim 132 , wherein R 1 is hexadecyl.

134 . The dry powder composition of claim 133 , wherein R 1 is linear hexadecyl.

135 . The dry powder composition of claim 132 , wherein the DSPE-PEG2000 is present at from about 0.03 wt % to about 2.1 wt % of the total weight of the dry powder composition.

136 . The dry powder composition of claim 132 , wherein the DSPE-PEG2000 is present at from about 0.05 wt % to about 1.5 wt % of the total weight of the dry powder composition.

137 . The dry powder composition of claim 132 , which comprises (a) about 1.5 wt % of the compound of Formula (I), (b) about 0.75 wt % of the DSPE-PEG2000, (c) about 29.30 wt % of the leucine, and (d) about 68.45 wt % of the mannitol, wherein R 1 is linear hexadecyl.

138 . A method for treating pulmonary hypertension in a patient in need thereof, comprising administering an effective amount of the dry powder composition of claim 132 to the lungs of the patient by inhalation via a dry powder inhaler.

139 . The method of claim 138 , wherein the pulmonary hypertension is pulmonary arterial hypertension.

140 . The method of claim 139 , wherein the pulmonary arterial hypertension is class I pulmonary arterial hypertension, as characterized by the New York Heart Association (NYHA).

141 . The method of claim 139 , wherein the pulmonary arterial hypertension is class II pulmonary arterial hypertension, as characterized by the NYHA.

142 . The method of claim 139 , wherein the pulmonary arterial hypertension is class III pulmonary arterial hypertension, as characterized by the NYHA.

143 . The method of claim 139 , wherein the pulmonary arterial hypertension is class IV pulmonary arterial hypertension, as characterized by the NYHA.

144 . The method of claim 138 , wherein the pulmonary hypertension is group 1 pulmonary hypertension, as characterized by the World Health Organization (WHO).

145 . The method of claim 138 , wherein the pulmonary hypertension is group 2 pulmonary hypertension, as characterized by the WHO.

146 . The method of claim 138 , wherein the pulmonary hypertension is group 3 pulmonary hypertension, as characterized by the WHO.

147 . The method of claim 138 , wherein the pulmonary hypertension is group 4 pulmonary hypertension, as characterized by the WHO.

148 . The method of claim 138 , wherein the pulmonary hypertension is group 5 pulmonary hypertension, as characterized by the WHO.

149 . The method of claim 138 , wherein the administering comprises aerosolizing the dry powder composition and administering an aerosolized dry powder composition to the lungs of the patient via inhalation, wherein the aerosolized dry powder composition comprises particles with an MMAD of from about 1 μm to about 3 μm, as measured by NGI.

150 . The method of claim 149 , wherein the aerosolized dry powder composition comprises particles with a fine particle fraction of from about 30% to about 60%, as measured by NGI.

151 . A system for treating pulmonary hypertension, portopulmonary hypertension, or pulmonary fibrosis, comprising:
the dry powder composition of claim 132 , and a dry powder inhaler (DPI).

Assignees

• Insmed Inc

Inventors

• Du Ju
• Plaunt Adam
• Malinin Vladimir

Classifications

• A61K31/5575

  having a cyclopentane, e.g. prostaglandin E2, prostaglandin F2-alpha · CPC title

• A61K9/0075 Primary

  for inhalation via a dry powder inhaler [DPI], e.g. comprising micronized drug mixed with lactose carrier particles · CPC title

• A61P9/12

  Antihypertensives · CPC title

• A61K47/183

  Amino acids, e.g. glycine, EDTA or aspartame · CPC title

• A61K31/5578

  having a pentalene ring system, e.g. carbacyclin, iloprost · CPC title