Nanocapsules comprising modified nucleobases and/or nucleosides, hydrogels and oleogels comprising them and uses thereof

Patent metadata

Field	Value
Publication number	US-12186433-B2
Application number	US-201816644275-A
Country	US
Kind code	B2
Filing date	Sep 7, 2018
Priority date	Sep 8, 2017
Publication date	Jan 7, 2025
Grant date	Jan 7, 2025

Abstract

The present invention concerns modified nucleobases, nucleosides, deoxynucleosides, and/or their derivatives, nanocapsules comprising them, hydrogels and oleogels comprising said nanocapsules or said above-mentioned compounds and their uses, in particular their pharmaceutical uses.

First claim

The invention claimed is:

1. A method for treating and/or preventing vascular disease, comprising administering to a mammal in need thereof a therapeutically effective amount of an hydrogel or an oleogel,
wherein said hydrogel comprises nanocapsules, an aqueous phase, and an active ingredient N in an aqueous phase of the hydrogel, said hydrogel having a G″/G′ inferior to 1, and said nanocapsules comprise at least one compound A and have a mean size diameter of less than 150 nm,
wherein said oleogel comprises at least one compound A an oily phase, and an active ingredient P in the oily phase of the oleogel, said oleogel having a G″/G′ ratio inferior to 1,
and wherein said compound A has the following formula (A):

wherein:
B is selected from the group consisting of a nucleobase, a nucleoside, a deoxynucleoside, and one of their derivatives, and
R is a linear or branched, saturated or unsaturated (C 9 -C 21 ) alkyl, said alkyl being optionally substituted by one or more substituent(s) selected from the group consisting of:
—COOH, —OH, —SH, —NH 2 , —COORa, —ORa, —SRa, and —NRaRb,
with Ra being a linear or branched, saturated or unsaturated (C 1 -C 10 ) alkyl, and Rb being H or a linear or branched, saturated or unsaturated (C 1 -C 10 ) alkyl, provided that said compound A is not:

2. The method of claim 1 , wherein compound A has a formula selected from the group consisting of:

with R being as defined in claim 1 .

3. The method of claim 1 , wherein said hydrogel or oleogel is administered locally.

4. The method of claim 1 , wherein said hydrogel or oleogel is a sustained release drug delivery system.

5. The method of claim 1 , wherein the vascular disease is vascular hyperplasia.

6. The method of claim 1 , wherein the vascular disease is intimal hyperplasia.

7. The method of claim 6 , wherein administration to a mammal in need thereof of the therapeutically effective amount of the hydrogel or the oleogel follows or replaces stent implantation.

8. A method for treating and/or preventing cancer, comprising administering to a mammal in need thereof a therapeutically effective amount of a hydrogel or an oleogel after resection of a solid tumor or by intratumoral administration,
wherein said hydrogel comprises nanocapsules, an aqueous phase, and an active ingredient N in the aqueous phase of the hydrogel, said hydrogel having a G″/G′ inferior to 1, and said nanocapsules comprises at least one compound A and have a mean size diameter of less than 150 nm,
wherein said oleogel comprises at least one compound A, an oily phase, and an active ingredient P in the oily phase of the oleogel, said oleogel having a G″/G′ ratio inferior to 1,
and wherein said compound A has the following formula (A):

wherein:
B is selected from the group consisting of a nucleobase, a nucleoside, a deoxynucleoside, and one of their derivatives, and
R is a linear or branched, saturated or unsaturated (C 9 -C 21 ) alkyl, said alkyl being optionally substituted by one or more substituent(s) selected from the group consisting of:
—COOH, —OH, —SH, —NH 2 , —COORa, —ORa, —SRa, and —NRaRb,
with Ra being a linear or branched, saturated or unsaturated (C 1 -C 10 ) alkyl, and Rb being H or a linear or branched, saturated or unsaturated (C 1 -C 10 ) alkyl, provided that said compound A is not:

9. The method of claim 8 , wherein compound A has a formula selected from the group consisting of:

10. The method of claim 8 , wherein said hydrogel or oleogel is administered locally.

11. The method of claim 8 , wherein said hydrogel or oleogel is a sustained release drug delivery system.

Assignees

• Univ Angers
• Inst Nat Sante Rech Med
• Centre Nat Rech Scient
• Centre Hospitalier Univ Dangers
• Univ Dangers France
• Centre Hospitalier Univ Dangers Cedex France

Inventors

• Pitorre Marion
• Bastiat Guillaume
• Bejaud Jérôme
• Benoit Jean-Pierre

Classifications

• C07H19/16

  Purine radicals · CPC title

• C07H19/06

  Pyrimidine radicals · CPC title

• A61K9/06

  Ointments; Bases therefor; {Other semi-solid forms, e.g. creams, sticks, gels (composition of ointments, creams or gels A61K47/00)} · 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

• A61K31/7068

  having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid · CPC title