Bioconjugates of neuropeptides derivatives

Patent metadata

Field	Value
Publication number	US-2021228724-A1
Application number	US-201917258701-A
Country	US
Kind code	A1
Filing date	Jul 18, 2019
Priority date	Jul 23, 2018
Publication date	Jul 29, 2021
Grant date	—

Abstract

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

First claim

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.

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 compound of squalene structure is squalenic acid and derivatives thereof, the derivative of squalenic acid being selected 1,1′,2-tris-nor-squalenic acid, 1,1′,2-tris-nor-squalenamine, 1,1′,2-tris-nor-squalenol, 1,1′,2-tris-nor-squalenethiol, squalene acetic acid, squalenylethanol, squalenylethanethiol and squalenylethylamine.

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 selected among the group comprising leucine enkephalin (LENK), methionine enkephalin (MENK), dalargin, kyotorphin, endomorphins, endorphins or a derivative thereof.

6 . The bioconjugate according to claim 1 , wherein the at least one neuropeptide and the at least one hydrocarbon compound of squalene structure are bond either to each other via a covalent bond or via a spacer or a function of the ester, disulfur, phosphate or amide bond.

7 . The bioconjugate according to claim 6 , wherein the spacer is selected among the group comprising dioxycarbonyl, diglycolate, carbonate, carbamate and amide spacer.

8 . The bioconjugate according to claim 1 , wherein the bioconjugate is chosen among:

9 . The bioconjugate according to claim 1 for use as a drug, preferably as an anti-hyperalgesic drug.

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

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

12 . The nanoparticle according to claim 11 , wherein the nanoparticle further comprises an anti-inflammatory compound.

13 . The nanoparticle according to claim 11 , wherein the nanoparticle has a mean diameter comprised between 10 and 500 nm, advantageously between 60 and 120 nm.

14 . A process for the preparation of a nanoparticle according to claim 11 , 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.

15 . 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 follow,

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, optionally in form of a nanoparticle according to claim 11 as active substance, and at least one pharmaceutically acceptable excipient and/or carrier.

16 . The pharmaceutical composition according to claim 15 for use in the treatment of pain disorders.

17 . A patch comprising a bioconmjugate 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, optionally in form of a nanoparticle according to claim 11 .

18 . The patch according to claim 17 , wherein the patch can be a patch equipped with micro-needles.

19 . The patch according to claim 17 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

• 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

• A61K47/54 Primary

  the modifying agent being an organic compound · CPC title

• A61K9/0021

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

• A61K38/00

  Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00) · CPC title

• C07K14/665

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