Polymeric synthetic antidote

Patent metadata

Field	Value
Publication number	US-2016193246-A1
Application number	US-201414911435-A
Country	US
Kind code	A1
Filing date	Aug 8, 2014
Priority date	Aug 29, 2013
Publication date	Jul 7, 2016
Grant date	—

Abstract

A polymer of formula (I) where X 1 and X 2 respectively represent the alpha and omega end groups of the polymer; R 1 represents a hydrogen atom or a straight or branched chain alkyl group; R 2 represents a straight or branched chain alkyl group which is substituted by a group which may have a positive charge at physiological pH; and n represents the number of repetitive units of the polymer, or a copolymer thereof; for use as a medicament and for treatment of a heparin overdose wherein the polymer of formula (I) has been found to have a selectivity and affinity for heparin.

First claim

1 . A polymer of formula (I):

where X 1 and X 2 respectively represent the alpha and omega end groups of the polymer;
R 1 represents a hydrogen atom or a straight or branched chain alkyl group, preferably a straight or branched chain alkyl group comprising from 1 to 6 carbon atoms, more preferably a methyl group;
R 2 represents a straight or branched chain alkyl group which is substituted by a group which may have a positive charge at a physiological pH; and
n represents the number of repetitive units of the polymer;
or a copolymer thereof;
for use as a medicament.

2 . The polymer for use according to claim 1 , wherein R 2 represents a straight or branched chain alkyl group comprising from 1 to 10 carbon atoms.

3 . The polymer for use according to claim 1 , wherein the substituent of R 2 has a positive charge at pH 7.4; preferably the substituent of R 2 is a group of formula —N(R 3 ) 2 wherein R 3 may be the same or different and represents a hydrogen atom or a straight or branched chain alkyl group; preferably the substituent R 3 may represent a straight or branched chain alkyl group; preferably the straight or branched chain alkyl group represented by R 3 may have from 1 to 6 carbon atoms.

4 . The polymer for use according to claim 1 , wherein the polymer is a co-polymer.

5 . The polymer for use according to claim 4 , wherein the co-polymer has a linear, dendritic, or grafted structure.

6 . The polymer for use according to claim 4 , wherein the co-polymer comprises a repetitive unit which is one or more of an ethylene glycol, an acrylate, a methacrylate, optionally carrying a polyethylene oxide (PEO), or a unit —(CH 2 —C(R 1 )(C(O)OR 4 ))— where R 4 represents a straight or branched chain alkyl group substituted by a group —N + (R 3 ) 3 .

7 . The polymer for use according to claim 1 , which is a polymer of formula (IV):

where X 1 , X 2 , R 1 , R 2 and n are as defined in claim 1 ; and X 3 represents an anion, for example OH − , Cl − ; HCO 3 − ; NO 3 − ; H 2 PO 4 − .

8 . The polymer for use according to claim 1 , which is in lyophilisate form.

9 . The polymer for use according to claim 1 , which has a mean charge density of from 1, preferably from 20 to 80%, preferably to 50%.

10 . The polymer for use according to claim 9 , which has a mean charge density from 15 to 30%.

11 . The polymer for use according to claim 1 , which has a molecular weight from 4000 to 10000 g/mol.

12 . The polymer for use according to claim 1 which comprises a repetitive unit which is N,N dimethyl amino ethyl methacrylate.

13 . The polymer for use according to claim 12 which is polydimethyl amino ethyl methacrylate.

14 . The polymer according to claim 1 for use in the treatment of a heparin overdose and/or for neutralisation of anticoagulation.

15 .- 16 . (canceled)

17 . A pharmaceutical composition comprising a polymer of formula (I) as claimed in claim 1 and a pharmaceutically acceptable diluent for use as a medicament; preferably for use in the treatment of a heparin overdose or for the neutralisation of heparin.

18 . A method of treating a heparin overdose or for neutralising anticoagulation which method comprises a step of administering to a human or animal in need of such treatment an effective amount of a polymer of formula (I) as defined in claim 1 .

19 . (canceled)

20 . A method of treating a heparin overdose or for neutralising anticoagulation which method comprises a step of administering to a human or animal in need of such treatment an effective amount of a pharmaceutical composition as defined in claim 17 .

Assignees

• Univ Liege

Inventors

• Grandfils Christian
• Flebus Lucas
• Sevrin Chantal

Classifications

• A61P39/02

  Antidotes · CPC title

• A61K31/727

  Heparin; Heparan · 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

• A61K47/34

  Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers (A61K47/10 takes precedence) · CPC title

• A61K31/785 Primary

  Polymers containing nitrogen · CPC title