Therapeutics for preterm labor management

Patent metadata

Field	Value
Publication number	US-10736880-B2
Application number	US-201616063312-A
Country	US
Kind code	B2
Filing date	Dec 19, 2016
Priority date	Dec 18, 2015
Publication date	Aug 11, 2020
Grant date	Aug 11, 2020

Abstract

Methods and compositions are provided for treating and preventing preterm labor using liposome encapsulated tocolytic agents, such as indomethacin. In certain aspects, targeted liposomes are provided that allow delivery of tocolytic agents directly to the uterus, such as by targeting to the oxytocin receptor.

First claim

What is claimed is:

1. A pharmaceutical composition comprising a tocolytic agent encapsulated in a liposome, wherein the liposome comprises a targeting moiety that binds to an oxytocin receptor, wherein the targeting moiety is an oxytocin receptor antagonist selected from the group consisting of atosiban, retosiban, barusiban or epelsiban and wherein the targeting moiety is conjugated to the surface of the liposome.

2. The pharmaceutical composition of claim 1 , wherein the tocolytic agent is an agent that crosses the placenta.

3. The pharmaceutical composition of claim 1 , wherein the tocolytic agent comprises β2-adrenergic agonist, a calcium-channel blocker, a oxytocin receptor antagonist (ORA), prostaglandin F2α receptor inhibitor, a nitric oxide donor or a nonsteroidal anti-inflammatory drug (NSAID).

4. The pharmaceutical composition of claim 3 , wherein the β2-adrenergic agonist comprises terbutaline, ritodrine, bedoradrine sulfate, MN-221, isoxsuprine, hexoprenaline, nylidrine, salbutamol or fenoterol.

5. The pharmaceutical composition of claim 3 , wherein the calcium-channel blocker comprises nifedipine or nicardipine.

6. The pharmaceutical composition of claim 3 , wherein the ORA comprises carbetocin, TC OT 39, WAY 267464 dihydrochloride, [Thr4]OT, [HO1][Thr4]OT, [Thr4,Gly7]OT and [HO1][Thr4,Gly7]OT.

7. The pharmaceutical composition of claim 3 , wherein the prostaglandin F2α receptor inhibitor comprises OBE-001, OBE-002 or PDC-31.

8. The pharmaceutical composition of claim 3 , wherein the NSAID comprises indomethacin, sulindac, ketorolac, celecoxib, rofecoxib or nimesulide.

9. The pharmaceutical composition of claim 8 , wherein the composition comprises indomethacin.

10. The pharmaceutical composition of claim 3 , wherein the Nitric oxide donor comprises sildenafil, nitric oxide or nitroglycerin.

11. The pharmaceutical composition of claim 1 , wherein the targeting moiety is conjugated to a PEGylated phospholipid.

12. The pharmaceutical composition of claim 11 , wherein the PEGylated phospholipid comprises 1,2-Distearoyl-sn-glycero-3-phosphoethanolamine (DSPE).

13. The pharmaceutical composition of claim 12 , wherein the PEGylated phospholipid comprises DSPE-PEG(2000) carboxylic acid.

14. The pharmaceutical composition of claim 13 , wherein the targeting moiety comprises DSPE-PEG(2000)-atosiban.

15. A method of treating a pregnant patient to slow or prevent preterm labor comprising administering to the patient an effective amount of the pharmaceutical composition of claim 1 .

Assignees

• Univ Texas
• Methodist Hospital
• The Board Of Regents Of The Univ Of Texas Systems

Inventors

• Refuerzo Jerrie S
• Godin Biana
• LONGO Monica

Classifications

• C07K7/16

  Oxytocins; Vasopressins; Related peptides · CPC title

• A61P15/06

  Antiabortive agents; Labour repressants · CPC title

• A61K47/62

  the modifying agent being a protein, peptide or polyamino acid · CPC title

• A61K9/127

  Synthetic bilayered vehicles, e.g. liposomes or liposomes with cholesterol as the only non-phosphatidyl surfactant · CPC title

• A61K9/0019

  Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00) · CPC title