Hydrogel compositions
AssigneesUniversity of Bradford, The University of Sheffield, Hyderabad Eye Institute
InventorsPrashant Garg, Stephen Rimmer, Charles William Ian Douglas
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Abstract
The present invention relates to hydrogel compositions comprising polymer conjugates capable of selectively binding to fungi, Gram positive bacteria and/or Gram negative bacteria. The hydrogel compositions can be used for detecting the presence of fungi, Gram positive bacteria and/or Gram negative bacteria in a sample.
Claims44
A hydrogel composition comprising a hydrogel polymeric matrix and a first polymer conjugate, or a salt thereof, having the general formula:
- P-[Q]x
- wherein:
- P is a branched temperature-responsive polymer comprising a plurality of functional groups, and wherein one or more of said functional groups are covalently attached to a ligand capable of binding to ergosterol;
- Q is a ligand capable of binding to ergosterol;
- and
- x is the percentage of functional groups on the branched temperature-responsive polymer, P, that are attached to Q, wherein x is greater than or equal to 10%;
- together with:
- (i) a second polymer conjugate, or a salt thereof, having the general formula:
- P1-[Q1]y
- wherein:
- P1 is a branched temperature-responsive polymer, comprising a plurality of functional groups, and wherein one or more of said functional groups are covalently attached to a ligand capable of binding to Gram positive bacteria;
- Q1 is a ligand capable of binding to Gram positive bacteria;
- and
- y is the percentage of functional groups on the branched temperature-responsive polymer, P1, that are attached to Q1, wherein y is greater than or equal to 10%;
- and/or
- (ii) a third polymer conjugate, or a salt thereof, having the general formula:
- P2-[Q2]z
- wherein:
- P2 is a branched temperature-responsive polymer, comprising a plurality of functional groups, and wherein one or more of said functional groups are covalently attached to a ligand capable of binding to Gram negative bacteria;
- Q2 is a ligand capable of binding to Gram negative bacteria;
- and
- z is the percentage of functional groups on the branched temperature-responsive polymer, P2, that are attached to Q2, wherein z is greater than or equal to 10%.
A hydrogel composition according to any one of the preceding claims, wherein Q is an antifungal agent capable of binding to ergosterol.
A hydrogel composition according to any one of the preceding claims, wherein Q is amphotericin B.
A hydrogel composition according to any one of the preceding claims, wherein x is greater than or equal to 50%.
A hydrogel composition according to any one of the preceding claims, wherein x is greater than or equal to 80%.
A hydrogel composition according to any one of the preceding claims, wherein Q1 is an antibacterial agent capable of binding to Gram positive bacteria.
A hydrogel composition according to any one of the preceding claims, wherein Q1 is vancomycin or a derivative thereof.
A hydrogel composition according to any one of the preceding claims, wherein y is greater than or equal to 50%.
A hydrogel composition according to any one of the preceding claims, wherein y is greater than or equal to 80%.
A hydrogel composition according to any one of the preceding claims, wherein Q2 is an antibacterial agent capable of binding to Gram negative bacteria.
A hydrogel composition according to any one of the preceding claims, wherein Q2 is polymyxin B or a related derivative capable of binding to lipopolysaccharide.
A hydrogel composition according to any one of the preceding claims, wherein z is greater than or equal to 50%.
A hydrogel composition according to any one of the preceding claims, wherein z is greater than or equal to 80%
A hydrogel composition according to any one of the preceding claims, wherein each Q, Q1 or Q2 group present is bound to a terminus of one of the branches of the polymer P, P1 or P2 respectively.
A hydrogel composition according to any one of the preceding claims, wherein each Q, Q1 or Q2 group present is bound to a terminus of one of the branches of the polymer P, P1 or P2 respectively by the reaction of a terminal functional group present on P, P1 or P2 with a functional group present on Q, Q1 or Q2 respectively to form a —NR1, —O—, —C(O)—O—, —O—C(O)—, —C(O)—NR1—, —NR1—C(O)—, —S—, —S(O)—, —S(O)2—, —S(O)2—NR1—, —NR1—S(O)2—, —N(H)C(O)O— or a triazole linking group, wherein R1 is hydrogen or (1-4C)alkyl.
A hydrogel composition according to any one of the preceding claims, wherein each Q, Q1 or Q2 group present is bound to a terminus of one of the branches of the polymer P, P1 or P2 respectively by the reaction of a terminal carboxy group present on P, P1 or P2 with an amine group present on Q, Q1 or Q2 to form a —C(O)—NH— linking group.
A hydrogel composition according to any one of the preceding claims, wherein P, P1 or P2 is a branched temperature-responsive homopolymer, co-polymer or graft co-polymer.
A hydrogel composition according to any one of the preceding claims, wherein P, P1 or P2 is a temperature-responsive polymer having branches occurring at every 3 to 30 monomer units.
A hydrogel composition according to any one of the preceding claims, wherein P, P1 or P2 is a temperature-responsive polymer having branches occurring at every 10 to 25 monomer units.
A hydrogel composition according to any one of the preceding claims, wherein each of P, P1 or P2 is branched temperature-responsive polymer formed from the polymerisation of:
- A) temperature-responsive monomers selected from the group consisting of N-substituted alkyl acrylamides and N-substituted alkyl methacrylamides (such as, for example, N-isopropylacrylamide and N-isopropylmethacrylamide), N,N-di-substituted alkyl acrylamide and N,N-di-substituted alkyl methacrylamides (such as, for example, N,N-isopropylacrylamide and N,N-isopropylmethacrylamide), methyl vinyl ethers, vinyl caprolactam, PEG acrylates, and amino acids (that form temperature-responsive peptides) or mixtures thereof;
- and B) optionally, one or more branching agents.
A hydrogel composition according to any one of the preceding claims, wherein P, P1 or P2 is a branched temperature-responsive polymer formed from the polymerisation of:
- A) temperature-responsive monomers selected from the group consisting of N-alkyl substituted acrylamides and N-alkyl substituted methacrylamides (such as, for example, N-isopropylacrylamide and N-isopropylmethacrylamide), N,N-di-alkyl substituted acrylamides and N,N-di-alkyl substituted methacrylamides (such as, for example, N,N-isopropylacrylamide and N,N-isopropylmethacrylamide), methyl vinyl ether, vinyl caprolactam, PEG acrylates or mixtures thereof;
- and B) optionally, one or more branching agents.
A hydrogel composition according to any one of the preceding claims, wherein P, P1 or P2 is temperature-responsive polymer formed from:
- A) monomers selected from the group consisting of N-isopropylacrylamide, N-isopropylmethacrylamide, methyl vinyl ether, vinyl caprolactam, PEG acrylates or a mixture thereof:
- and B) optionally, one or more branching agents.
A hydrogel composition according to any one of the preceding claims, wherein P, P1 or P2 is temperature-responsive polymer formed from:
- A) N-isopropylacrylamide (i.e. the polymer is poly(N-isopropylacrylamide));
- and B) one or more branching agents.
A hydrogel composition according to any one of the preceding claims, wherein P is branched poly(N-isopropylacrylamide) and Q is amphotericin B.
A hydrogel composition according to any one of the preceding claims, wherein the first polymer conjugate P-[Q]x has the formula:
- wherein the group in the square brackets is amphotericin B and P and x are each as defined in any one of the preceding claims.
A hydrogel composition according to any one of the preceding claims, wherein P1 is branched poly(N-isopropylacrylamide) and Q1 is vancomycin.
A hydrogel composition according to any one of the preceding claims, wherein P2 is branched poly(N-isopropylacrylamide) and Q2 is polymyxin B.
A hydrogel composition according to any one of the preceding claims, wherein the water content of the hydrogel is greater than 50% w/w.
A contact lens, membrane, swab or wound dressing comprising a hydrogel composition according to any one of the preceding claims.
Dependencies are inferred from the claim text.