Bioconjugates of neuropeptides derivatives

Patent metadata

Field	Value
Publication number	US-11590232-B2
Application number	US-201917258701-A
Country	US
Kind code	B2
Filing date	Jul 18, 2019
Priority date	Jul 23, 2018
Publication date	Feb 28, 2023
Grant date	Feb 28, 2023

Abstract

A bioconjugate comprising at least one neuropeptide covalently bond to at least one hydrocarbon compound of squalene structure.

First claim

The invention claimed is:

1. A bioconjugate comprising at least one neuropeptide covalently bond to at least one hydrocarbon compound of squalene structure (SQ), as represented as follows,

wherein:
m1 is 0,1,2,3,4,5,6,7,8, or 9, and
m2 is 0,1,2,3,4,5,6,7,8, or 9,

and wherein

represents the bond to the at least one neuropeptide, and
wherein the at least one neuropeptide has a C-terminal acid covalently bonded to the at least one hydrocarbon compound of squalene structure by using a dioxycarbonyl spacer or the at least one neuropeptide has a N-terminal amine covalently bonded to the at least one hydrocarbon compound of squalene structure by using a diglycolate spacer.

2. The bioconjugate according to claim 1 , wherein the at least one hydrocarbon compound of squalene structure comprises from 11 to 102 carbon atoms.

3. The bioconjugate according to claim 1 , wherein the at least one hydrocarbon-based of squalene structure able to form said bioconjugate is squalenic acid or a squalenic acid derivative, wherein the squalenic acid derivative is selected from the group consisting of 1,1′,2-tris-nor-squalenic acid, 1,1′,2-tris-nor-squalenol, 1,1′,2-tris-nor-squalenethiol, squalene acetic acid, squalenylethanol, and squalenylethanethiol.

4. The bioconjugate according to claim 1 , wherein the at least one neuropeptide is an opioid peptide.

5. The bioconjugate according to claim 4 , wherein the opioid peptide is leucine enkephalin (LENK).

6. The bioconjugate according to claim 4 , wherein the opioid peptide is selected from the group consisting of methionine enkephalin (MENK), dalargin, kyotorphin, endomorphins, endorphins and a derivative thereof.

7. The bioconjugate according to claim 1 , wherein the at least one neuropeptide has a N-terminal amine covalently bonded to the at least one hydrocarbon compound of squalene structure by using a diglycolate spacer and the at least one hydrocarbon compound of squalene structure is derived from the molecule of 1,1′,2-tris-nor-squalenol.

8. The bioconjugate according to claim 1 , wherein the at least one neuropeptide has a C-terminal acid covalently bonded to the at least one hydrocarbon compound of squalene structure by using a dioxycarbonyl spacer and the at least one hydrocarbon compound of squalene structure is derived from the molecule of 1,1′,2-tris-nor-squalenic acid.

9. The bioconjugate according to claim 1 , wherein the bioconjugate is

10. The bioconjugate according to claim 1 , wherein the bioconjugate is:

11. The bioconjugate according to claim 1 for use as a drug.

12. The bioconjugate according to claim 1 for use in the treatment of pain disorders.

13. A pharmaceutical composition comprising a bioconjugate comprising at least one neuropeptide covalently bond to at least one hydrocarbon compound of squalene structure (SQ), as represented as follows,

wherein:
m1 is 0,1,2,3,4,5,6,7,8, or 9, and
m2 is 0,1,2,3,4,5,6,7,8, or 9,

and wherein

represents the bond to the at least one neuropeptide, and
wherein the at least one neuropeptide has a C-terminal acid covalently bonded to the at least one hydrocarbon compound of squalene structure by using a dioxycarbonyl spacer or the at least one neuropeptide has a N-terminal amine covalently bonded to the at least one hydrocarbon compound of squalene structure by using a diglycolate spacer,
as an active substance, and at least one pharmaceutically acceptable excipient and/or carrier.

14. The pharmaceutical composition according to claim 13 for use in the treatment of pain disorders.

15. A nanoparticle comprising the bioconjugate according to claim 1 .

16. The nanoparticle according to claim 15 , wherein the nanoparticle further comprises an anti-inflammatory compound.

17. The nanoparticle according to claim 15 , wherein the nanoparticle has a mean diameter between 10 and 500 nm.

18. A process for the preparation of a nanoparticle according to claim 15 , the process comprising at least:
dispersion of the bioconjugate in at least one organic solvent at a concentration sufficient to obtain, on adding the corresponding mixture, with stirring, to an aqueous phase, instantaneous formation of nanoparticles in suspension in said aqueous phase, and
isolation of said nanoparticles.

19. A patch comprising a bioconjugate of claim 1 optionally in a form of a nanoparticle.

20. The patch according to claim 19 , wherein the patch is a patch equipped with micro-needles.

21. The patch according to claim 19 for use in the treatment of pain disorders.

Assignees

• Centre Nat Rech Scient
• Univ Paris Saclay

Inventors

• Couvreur Patrick
• Feng Jiao
• Lepetre-Mouelhi Sinda

Classifications

• A61K47/6929

  the form being a nanoparticle, e.g. an immuno-nanoparticle · CPC title

• A61K9/0021

  Intradermal administration, e.g. through microneedle arrays or needleless injectors · CPC title

• A61K38/33

  derived from pro-opiomelanocortin, pro-enkephalin or pro-dynorphin · CPC title

• A61K47/54 Primary

  the modifying agent being an organic compound · CPC title

• A61K9/5123

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