Medical devices for delivering a therapeutic agent and method of preparation

• US 7,419,696 B2
• Filed: 11/30/2005
• Issued: 09/02/2008
• Est. Priority Date: 04/26/1993
• Status: Expired due to Fees

• Current Assignee: Medtronic Incorporated (Medtronic Plc)
• Original Assignee: Medtronic Incorporated (Medtronic Plc)
• Inventors: Berg, Eric P., Dror, Michael, Tuch, Ronald J., Wolff, Rodney G.
• Primary Examiner(s): Fletcher, III; William P.
• Assistant Examiner(s): Sellman; Cachet I
• Application Number:
  US11/292,171
• Publication Number:
  US 20060085064A1
• Time in Patent Office: 1,007 Days
• Field of Search: 427/2.1, 427/2.14, 427/2.24, 427/2.25, 427/2.28, 427/427.4, 427/372.2, 427/379
• US Class Current: 427/2.24
• CPC Class Codes: A61F 2/82 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; instruments specially adapted for placement or removal of stents or stent-grafts A61F2/95; for closing wounds, or holding wounds closed A61B17/04 - A61B17/115; dilators A61M29/00
• CPC Class Codes: A61F 2/88 the wire-like elements formed as helical or spiral coils forming a net-like or mesh-like structure A61F2/90
• CPC Class Codes: A61F 2/958 Inflatable balloons for placing stents or stent-grafts
• CPC Class Codes: A61F 2210/0004 bioabsorbable
• CPC Class Codes: A61F 2240/001 Designing or manufacturing processes
• CPC Class Codes: A61F 2250/0067 Means for introducing or releasing pharmaceutical products into the body
• CPC Class Codes: A61L 2300/236 Glycosaminoglycans, e.g. heparin, hyaluronic acid, chondroitin
• CPC Class Codes: A61L 2300/42 Anti-thrombotic agents, anticoagulants, anti-platelet agents
• CPC Class Codes: A61L 2300/432 Inhibitors, antagonists A61L2300/402 - A61L2300/43 take precedence
• CPC Class Codes: A61L 29/041 obtained by reactions only involving carbon-to-carbon unsaturated bonds
• CPC Class Codes: A61L 29/044 Proteins; Polypeptides; Degradation products thereof
• CPC Class Codes: A61L 29/06 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
• CPC Class Codes: A61L 29/145 Hydrogels or hydrocolloids
• CPC Class Codes: A61L 29/146 Porous materials, e.g. foams or sponges
• CPC Class Codes: A61L 29/16 Biologically active materials, e.g. therapeutic substances A61L29/048 takes precedence
• CPC Class Codes: A61L 31/042 Polysaccharides
• CPC Class Codes: A61L 31/043 Proteins; Polypeptides; Degradation products thereof
• CPC Class Codes: A61L 31/048 obtained by reactions only involving carbon-to-carbon unsaturated bonds A61L31/041 takes precedence
• CPC Class Codes: A61L 31/06 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds A61L31/041 takes precedence
• CPC Class Codes: A61L 31/10 Macromolecular materials
• CPC Class Codes: A61L 31/145 : Hydrogels or hydrocolloids
• CPC Class Codes: A61L 31/146 : Porous materials, e.g. foams or sponges
• CPC Class Codes: A61L 31/16 : Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence

Abstract

A method for making an intravascular stent by applying to the body of a stent a solution which includes a solvent, a polymer dissolved in the solvent and a therapeutic substance dispersed in the solvent and then evaporating the solvent. The inclusion of a polymer in intimate contact with a drug on the stent allows the drug to be retained on the stent during expansion of the stent and also controls the administration of drug following implantation. The adhesion of the coating and the rate at which the drug is delivered can be controlled by the selection of an appropriate bioabsorbable or biostable polymer and the ratio of drug to polymer in the solution. By this method, drugs such as dexamethasone can be applied to a stent, retained on a stent during expansion of the stent and elute at a controlled rate.

Claims

1. A method for making an intravascular stent comprising the steps of:

(a) providing a radially expandable stent body;

(b) applying to the stent body a mixture of a solvent, a polymer, and a therapeutic substance;

(c) evaporating the solvent; and

(d) repeating application and evaporating steps (b) and (c) to provide an amount of polymer and therapeutic substance on the stent body,

wherein the stent body retains the polymer and therapeutic substance when the stent body is radially expanded.

2. The method according to claim 1, wherein the stent body has a metal surface.

3. The method according to claim 1, wherein the mixture is applied to the stent body by spraying.

4. The method according to claim 1, wherein the mixture is applied to the stent body by dipping.

5. The method according to claim 1, wherein the polymer is selected from the group consisting of silicones, polyurethanes, polyesters, vinyl homopolymers and copolymers, acrylate homopolymers and copolymers, polyethers and cellulosics.

6. The method according to claim 1, wherein the ratio of therapeutic substance to polymer in the mixture is in the range of about 10:

1 to 1;

100.

7. The method according to claim 1, wherein the therapeutic substance is selected from the group consisting of glucocorticoids, dexamethasone, dexamethasone sodium phosphate, anticoagulants, heparin, hirudin, tick anticoagulant peptide, angiopeptin, antimitotic agents, and oligonucleotides.

8. A method for making an intravascular stent having a radially expandable stent body with a mixture of a solvent, a polymer, and a therapeutic substance applied thereto, and the stent body retains the polymer and therapeutic substance when the stent body is radially expanded, said method of making comprising the steps of:

(a) providing the radially expandable stent body;

(b) applying to the stent body the mixture of the solvent, the polymer, and the therapeutic substance;

(c) evaporating the solvent; and

(d) repeating application and evaporating steps (b) and (c) to provide an amount of polymer and therapeutic substance on the stent body.

9. The method according to claim 8, wherein the stent body has a metal surface.

10. The method according to claim 8, wherein the stent body is balloon expandable.

11. The method according to claim 8, wherein the mixture is applied to the stent body by spraying.

12. The method according to claim 8, wherein the mixture is applied to the stent body by dipping.

13. The method according to claim 8, wherein the polymer is selected from the group consisting of silicones, polyurethanes, polyesters, vinyl homopolymers and copolymers, acrylate homopolymers and copolymers, polyethers and cellulosics.

14. The method according to claim 8, wherein the ratio of therapeutic substance to polymer in the mixture is in the range of about 10:

1 to 1;

100.

15. The method according to claim 8, wherein the therapeutic substance is selected from the group consisting of glucocorticoids, dexamethasone, dexamethasone sodium phosphate, anticoagulants, heparin, hirudin, tick anticoagulant peptide, angiopeptin, antimitotic agents, and oligonucleotides.

16. A method for making an intravascular stent having a cylindrical, balloon expandable metal stent body with a mixture of a solvent, a polymer, and a therapeutic substance applied thereto, and the stent body retains the polymer and therapeutic substance when the stent body is radially expanded, said method comprising the steps of:

(a) providing the cylindrical, balloon expandable metal stent body;

(b) spraying onto the stent body the mixture of the solvent, the polymer, and therapeutic substance;

(c) evaporating the solvent; and

(d) repeating application and evaporating steps (b) and (c) to provide an amount of polymer and therapeutic substance on the stent body.

17. The method according to claim 16, wherein the polymer is selected from the group consisting of silicones, polyurethanes, polyesters, vinyl homopolymers and copolymers, acrylate homopolymers and copolymers, polyethers and cellulosics.

18. The method according to claim 16, wherein the ratio of therapeutic substance to polymer in the mixture is in the range of about 10:

1 to 1;

100.

19. The method according to claim 16, wherein the therapeutic substance is selected from the group consisting of glucocorticoids, dexamethasone, dexamethasone sodium phosphate, anticoagulants, heparin, hirudin, tick anticoagulant peptide, angiopeptin, antimitotic agents, and oligonucleotides.