Hollow stent filled with a therapeutic agent formulation

Patent metadata

Field	Value
Publication number	US-9901663-B2
Application number	US-201414267620-A
Country	US
Kind code	B2
Filing date	May 1, 2014
Priority date	May 6, 2013
Publication date	Feb 27, 2018
Grant date	Feb 27, 2018

Abstract

A composition for loading into a structural element of a stent, where the structural element is defined by a lumen and at least one opening to access the lumen. The composition may comprise a therapeutic agent, and a chelator, a precipitation agent, or a combination thereof. Medical devices, such as stents, with a structural element defined by a lumen and at least one opening to access the lumen, filled with the compositions are also described.

First claim

What is claimed is:

1. A medical device, the device comprising:
a device body comprising at least one structural element, the structural element comprising a lumen and at least one opening to access the lumen; and
a composition within the lumen, the composition comprising a therapeutic agent, and a metal ion stabilizer;
wherein the at least one structural element has walls, the walls forming an interior surface and the lumen being surrounded by the interior surface;
wherein the composition comprises at least 0.1 μg of the metal ion stabilizer/cm 2 of the interior surface surrounding the lumen and not more than 15 μg metal of the ion stabilizer/cm 2 of the interior surface surrounding the lumen;
and
wherein the medical device is a stent.

2. The medical device of claim 1 , wherein the metal ion stabilizer comprises a metal chelator.

3. The medical device of claim 1 , wherein the metal ion stabilizer comprises a precipitation agent.

4. The medical device of claim 1 , wherein the device body is biostable.

5. The medical device of claim 1 , wherein the device body is formed of a biostable metal selected from the group consisting of 316L stainless steel, CoNi MP35N, CoCr L-605, elgiloy, nitinol, FePtCr, and combinations thereof.

6. The medical device of claim 1 , wherein the interior surface of the at least one structural element of the stent body is not electropolished, or a degree of electropolishing of the interior surface of the at least one structural element is less than the outer surface of the stent.

7. The medical device of claim 1 , wherein the therapeutic agent belongs to a macrolide lactone family and the therapeutic agent contains a triene moiety.

8. The medical device of claim 1 , wherein the therapeutic agent is selected from the group consisting of rapamycin, everolimus, Biolimus A9, umirolimus, ridaforolimus, tacrolimus, temsirolimus, pimecrolimus, novolimus, merilimus, zotarolimus, 40-O-(3-hydroxypropyl)rapamycin, 40-O-[2-(2-hydroxy)ethoxy]ethyl-rapamycin, 40-O-tetrazolylrapamycin, 40-epi-(N1-tetrazolyl)-rapamycin, and combinations thereof.

9. The medical device of claim 1 , wherein the metal ion stabilizer comprises a chelator selected from the group consisting of ethylene diamine tetraacetic acid (EDTA), calcium disodium EDTA, EDTA with a counterion of potassium, EDTA with a counterion of ammonium, EDTA with a counterion of a quaternary ammonium compound, 2,3-dimereapto-1-propanesulfonic acid, dimercaptosuccinic acid, dimercaprol, desferrioxamine mesylate, alpha lipoic acid, nitrilotriacetate, penicillamine, thiamine tetrahydrofurfiuyl disulfide, deferiprone, deferasirox, kojic acid, bisphosphonates, 3-hydroxy-4-pyridinecarboxylic acid, 4-hydroxy-3-pyridinecarboxylic acid, 1,6-Dimethyl-4-hydroxy-3-pyridinecarboxylic acid, 4-hydroxy-2-methyl-3-pyridinecarboxylic acid, and combinations thereof.

10. The medical device of claim 1 , wherein the metal ion stabilizer comprises a chelator selected from the group consisting of sodium ascorbate, desferrioxamine, malic acid, citric acid, succinic acid, sodium, calcium, and magnesium salts of malic acid, citric acid, and succinic acid, feralex-G, clioquinol, curcumin, epigallocatechin, 3-hydroxy-4-pyridinone, 3-hydroxy-4-pyridinecarboxylic acid, 4-hydroxy-3-pyridinecarboxylic acid, 1,6-Dimethyl-4-hydroxy-3-pyridinecarboxylic acid, 4-hydroxy-2-methyl-3-pyridinecarboxylic acid, and combinations thereof.

11. The medical device of claim 1 , wherein the metal ion stabilizer comprises a precipitation agent selected from the group consisting of stearic acid, lauric acid, capric acid, and caprylic acid, and sodium, calcium, and magnesium salts thereof, and combinations thereof.

12. The medical device of claim 1 , wherein a combination of the therapeutic agent and the metal ion stabilizer comprises at least 50 wt % of the composition, at least 70 wt % of the composition, or at least 90 wt % of the composition.

13. The medical device of claim 1 , wherein at least 90% of the volume of the lumen is filled with the composition.

14. The medical device of claim 1 , wherein the metal ion stabilizer is selected from the group consisting of 2,3-dimereapto-1-propanesulfonic acid, dimercaptosuccinic acid, dimercaprol, desferrioxamine mesylate, alpha lipoic acid, nitrilotriacetate, penicillamine, thiamine tetrahydrofurfiuyl disulfide, deferiprone, deferasirox, kojic acid, bisphosphonates, 3-hydroxy-4-pyridinecarboxylic acid, 4-hydroxy-3-pyridinecarboxylic acid, 1,6-Dimethyl-4-hydroxy-3-pyridinecarboxylic acid, 4-hydroxy-2-methyl-3-pyridinecarboxylic acid, desferrioxamine, succinic acid, sodium, calcium, and magnesium salts of succinic acid, feralex-G, clioquinol, curcumin, epigallocatechin, stearic acid, lauric acid, capric acid, and caprylic acid, and sodium, calcium, and magnesium salts of stearic acid, lauric acid, capric acid, and caprylic acid, and combinations thereof.

15. The medical device of claim 1 , wherein the at least one opening comprises one or more side openings to access the lumen and allow the therapeutic agent to be released from the lumen, and the side openings one or more being only on the abluminal side of the medical device.

16. A stent comprising:
a plurality of interconnected structural elements comprising a metallic material, wherein at least some of the structural elements are annular and comprise an interior lumen;
and
a therapeutic agent and an additive disposed within the interior lumen(s);
wherein an inner surface of the annular structural element(s) is susceptible to release of metal ions which are capable of degrading the therapeutic agent;
wherein the additive is for protecting the therapeutic agent from degradation by the metal ions by rendering the metal ions unable to interact with the therapeutic agent;
wherein the additive is present at an amount of at least 0.1 μg/cm 2 of the inner surface and not more than 15 μg/cm 2 of the inner surface; and
wherein the additive is selected from the group consisting of 2,3-dimereapto-1-propanesulfonic acid, dimercaptosuccinic acid, dimercaprol, desferrioxamine mesylate, alpha lipoic acid, nitrilotriacetate, thiamine tetrahydrofurfiuyl disulfide, deferiprone, deferasirox, kojic acid, bisphosphonates, 3-hydroxy-4-pyridinecarboxylic acid, 4-hydroxy-3-pyridinecarboxylic acid, 1,6-Dimethyl-4-hydroxy-3-pyridinecarboxylic acid, 4-hydroxy-2-methyl-3-pyridinecarboxylic acid, desferrioxamine, succinic acid, sodium, calcium, and magnesium salts of succinic acid, feralex-G, clioquinol, epigallocatechin, 3-hydroxy-4-pyridinone, stearic acid, lauric acid, capric acid, and caprylic acid, and sodium, calcium, and magnesium salts of stearic acid, lauric acid, capric acid, and caprylic acid, and combinations thereof.

17. The stent of claim 16 , wherein the therapeutic agent is degraded by not more than 5 wt % at the end of the shelf-life of the stent, and wherein the shelf-life of the stent is at least 6 months, at least 9 months, at least 12 months, at least 18 months, or at least 24 months.

18. The stent of claim 16 , wherein the additive is selected from the group consisting of 2,3-dimereapto-1-propanesulfonic acid, dimercaptosuccinic acid, dimercaprol, desferrioxamine mesylate, alpha lipoic acid, nitrilotriacetate, thiamine tetrahydrofurfiuyl disulfide, deferiprone, deferasirox, kojic acid, 3-hydroxy-4-pyridinecarboxylic acid, 4-hydroxy-3-pyridinecarboxylic acid, 1,6-Dimethyl-4-hydroxy-3-pyridinecarboxylic acid, 4-hydroxy-2-methyl-3-pyridinecarboxylic acid, desferrioxamine, feralex-G, clioquinol, epigallocatechin, and combinations thereof.

19

Assignees

• Abbott Cardiovascular Systems Inc

Inventors

• Pacetti Stephen D
• Ding Ni

Classifications

• A61F2/82

  Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents (stent-grafts for tubular structures of the body other than blood vessels A61F2/04; stent-grafts for blood vessels A61F2/07) · CPC title

• A61F2250/0067

  Means for introducing or releasing pharmaceutical products into the body · CPC title

• A61L31/143

  Stabilizers · CPC title

• A61L2300/00

  Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices · CPC title

• A61L27/50

  Materials characterised by their function or physical properties {, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials} · CPC title