Compositions and methods for reducing neointima formation
AssigneeUniversity of Georgia Research Foundation, Inc.
InventorsShiyou Chen, Rui Tang
Life of this patent
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Abstract
Compositions, devices, grafts and methods for reducing or preventing anti-neointima following cardiovascular injuries and interventions are disclosed. The compositions, devices, and grafts typically include an effective amount of a CTP synthase 1 inhibitor to reduce proliferation of vascular smooth muscle cells, without substantial reducing the proliferation of endothelial cells. Methods of reducing neointima formation, accelerating re-endothelialization, and reducing restenosis in a subject using the compositions, devices, and grafts are also disclosed.
Claims24
(canceled)
The method of claim 16, wherein the amount of the combination is not sufficient to reduce proliferation of endothelial cells in the subject.
The method of claim 16, wherein the nucleoside analog is selected from the group consisting of cyclopentenyl cytosine (CPEC), cyclopentenyl cytosine 5′-triphosphate (CPEC-TP), 3-deazauridine (3-DU), carbodine, pharmacologically active salts thereof.
The method of claim 21, wherein the CTPS1 inhibitor is a nucleoside analog selected from the group consisting of cyclopentenyl cytosine (CPEC), cyclopentenyl cytosine 5′-triphosphate (CPEC-TP), 3-deazauridine (3-DU), carbodine, and pharmacologically active salts thereof.
-8. (canceled)
The method of claim 16, wherein the nucleoside analog is incorporated into or encapsulated in a delivery vehicle for delivering the nucleoside analog to vascular smooth muscle cells.
The method of claim 16, wherein a targeting signal for enhancing delivery of the nucleoside analog to vascular smooth muscle cells is (i) operably linked to the nucleoside analog, or (ii) operably linked to the delivery vehicle for delivering the nucleoside analog to vascular smooth muscle cells.
The method of claim 21, wherein the nucleoside analog is coated onto or incorporated into the device.
The method of claim 21, wherein the device is selected from the group consisting of implants, stents, and valves.
A method of reducing proliferation of vascular smooth muscle cells or reducing neointima formation in a subject comprising
- administering to the subject cytidine in combination with a nucleoside analog that inhibits CTP synthase 1,
- wherein the combination of cytidine and the nucleoside analog are administered to the subject in an effective amount to reduce proliferation of vascular smooth muscle cells (VSMC) in the subject to a greater degree than the combination reduces proliferation of endothelial cells (EC) in the subject.
The method of claim 21, wherein the site of implantation or a site adjacent thereto comprises an injury in need of re-endothelialization, and wherein re-endothelialization occurs faster in the presence of the device than a control device without the nucleoside analog.
(canceled)
(canceled)
A method of reducing proliferation of vascular smooth muscle cells or reducing neointima formation in a subject comprising
- administering to the subject cytidine in combination with cyclopentenyl cytosine (CPEC),
- wherein the combination of the CPEC and the cytidine are administered to the subject in an effective amount to reduce proliferation of vascular smooth muscle cells (VSMC) in the subject to a greater degree than the combination reduces proliferation of endothelial cells (EC) in the subject,
- wherein the CPEC is administered by implanting a medical device comprising the nucleotide analog into the subject.
Dependencies are inferred from the claim text.