Methods For Increasing Blood Flow And/Or Promoting Tissue Regeneration
AssigneeGenzyme Corporation
InventorsGary J. BRIDGER, Simon P. FRICKER
Life of this patent
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Abstract
Methods for increasing blood flow and/or regenerating tissue using compounds which bind to the chemokine receptor CXCR4 are disclosed. Preferred embodiments of such compounds are of the formula Z-linker-Z′ (1).
Claims26
A method for regenerating tissue in a subject, comprising directly administering mobilized and harvested progenitor and/or stem cells to damaged tissues in said subject, wherein the progenitor and/or stem are mobilized by a compound having formula (1)
- Z-linker-Z′ (1)
- wherein Z is a cyclic polyamine containing 9-32 ring members of which 2-8 are nitrogen atoms, said nitrogen atoms separated from each other by at least 2 carbon atoms, and wherein said heterocycle may optionally contain additional heteroatoms besides nitrogen and/or may be fused to an additional ring system;
- or Z is of the formula
- wherein A comprises a monocyclic or bicyclic fused ring system containing at least one N and B is H or an organic moiety of 1-20 atoms;
- Z′ may be embodied in a form as defined by Z above, or alternatively may be of the formula
- —N(R)—(CR2)n—X
- wherein each R is independently H or straight, branched or cyclic alkyl (1-6C),
- n is 1 or 2, and
- X is an aromatic ring, including heteroaromatic rings, or is a mercaptan;
- or Z1 is of the formula —Ar(Y)j;
- wherein Ar is an aromatic or heteroaromatic moiety, and each Y is independently a non-interfering substituent and j is 0-3;
- “linker” represents a bond, alkylene (1-6C) or may comprise aryl, fused aryl, oxygen atoms contained in an alkylene chain, or may contain keto groups or nitrogen or sulfur atoms.
-32. (canceled)
A method for increasing blood flow in a subject, comprising directly administering mobilized and harvested progenitor and/or stem cells to a target tissue in said subject that is in need of increased blood flow, wherein the progenitor and/or stem are mobilized by a compound having formula (1)
- Z-linker-Z′ (1)
- wherein Z is a cyclic polyamine containing 9-32 ring members of which 2-8 are nitrogen atoms, said nitrogen atoms separated from each other by at least 2 carbon atoms, and wherein said heterocycle may optionally contain additional heteroatoms besides nitrogen and/or may be fused to an additional ring system;
- or Z is of the formula
- wherein A comprises a monocyclic or bicyclic fused ring system containing at least one N and B is H or an organic moiety of 1-20 atoms;
- Z′ may be embodied in a form as defined by Z above, or alternatively may be of the formula
- —N(R)—(CR2)n—X
- wherein each R is independently H or straight, branched or cyclic alkyl (1-6C),
- n is 1 or 2, and
- X is an aromatic ring, including heteroaromatic rings, or is a mercaptan;
- or Z1 is of the formula —Ar(Y)j;
- wherein Ar is an aromatic or heteroaromatic moiety, and each Y is independently a non-interfering substituent and j is 0-3;
- “linker” represents a bond, alkylene (1-6C) or may comprise aryl, fused aryl, oxygen atoms contained in an alkylene chain, or may contain keto groups or nitrogen or sulfur atoms;
- thereby increasing said blood flow in said tissue.
The use of a compound having formula (1) for the manufacture of a medicament for increasing blood flow in a target tissue, wherein said compound having formula (1) is capable of mobilizing progenitor and/or stem cells, which are harvested and directly administered to target tissues in a subject.
Dependencies are inferred from the claim text.