Drug delivery medical device

• US 10,117,972 B2
• Filed: 07/12/2012
• Issued: 11/06/2018
• Est. Priority Date: 07/15/2011
• Status: Active Grant

• Current Assignee: Micell Medtech Incorporated
• Original Assignee: Micell Technologies Inc.
• Inventors: McClain, James B., Taylor, Charles Douglas, Zani, Brett G., Neet, John, Kiorpes, Timothy Charles
• Primary Examiner(s): Young, Micah Paul
• Application Number:
  US14/131,878
• Publication Number:
  US 20140350522A1
• Time in Patent Office: 2,308 Days
• CPC Class Codes: A61B 17/12136 Balloons
• CPC Class Codes: A61L 2300/602 Type of release, e.g. controlled, sustained, slow
• CPC Class Codes: A61L 2420/06 Coatings containing a mixture of two or more compounds
• CPC Class Codes: A61L 29/085 Macromolecular materials
• CPC Class Codes: A61L 29/16 Biologically active materials, e.g. therapeutic substances A61L29/048 takes precedence
• CPC Class Codes: A61L 31/08 Materials for coatings
• CPC Class Codes: A61L 31/16 Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence
• CPC Class Codes: A61M 2025/1081 having sheaths or the like for covering the balloon but not forming a permanent part of the balloon, e.g. retractable, dissolvable or tearable sheaths
• CPC Class Codes: A61M 2210/12 Blood circulatory system
• CPC Class Codes: A61M 25/10 Balloon catheters A61M25/0125 takes precedence; embolectomy A61B17/22032; retractors A61B17/02; inflatable balloons for placing stents or stent-grafts A61F2/958 ; stomach balloons for treatment of obesity A61F5/0003; oesophagal tubes A61J15/00
• CPC Class Codes: B05D 7/24 for applying particular liquids or other fluent materials

Abstract

Provided is a coated implantable medical device, comprising: a substrate; and a coating disposed on the substrate, wherein the coating comprises at least one polymer and at least one pharmaceutical agent in a therapeutically desirable morphology and/or at least one active biological agent and optionally, one or more pharmaceutical carrying agents; wherein substantially all of pharmaceutical agent and/or active biological agent remains within the coating and on the substrate until the implantable device is deployed at an intervention site inside the body of a subject and wherein upon deployment of the medical device in the body of the subject a portion of the pharmaceutical agent and/or active biological agent is delivered at the intervention site along with at least a portion of the polymer and/or a at least a portion of the pharmaceutical carrying agents.

Claims

1. A medical device comprising:

a balloon; and

a coating on at least a portion of the balloon,

wherein the coating comprises a polymer, a macrolide immunosuppressive drug in crystalline form present on an exterior surface of the coating and a cationic binding agent, and

wherein the device releases at least 3% of the active agent to a treatment site upon inflation of the balloon in vivo.

2. The medical device of claim 1 wherein the device releases at least 5% or at least 10% of the active agent to the treatment site in vivo.

3. The medical device of claim 1 wherein the binding agents comprises at least one of:

Polyarginine, Polyarginine 9-L-pArg, DEAE-Dextran (Diethylaminoethyl cellulose-Dextran), DMAB (Didodecyldimethylammonium bromide), PEI (Polyethyleneimine), TAB (Tetradodecylammonium bromide), and DMTAB (Dimethylditetradecylammonium bromide).

4. The medical device of claim 1 wherein an average molecular weight of the binding agent or a size of the active agent in the coating is controlled.

5. The medical device of claim 1 wherein the active agent is sirolimus and wherein the sirolimus has have an average size of about 1.5 μ

m, about 2.5 μ

m, about 645 nm, or about 100-200 nm.

6. The medical device of claim 1 wherein a ratio of the active agent to the binding agent is 1:

1, 1;

2, 1;

3, 1;

4, 1;

5, 1;

10, 1;

20, 2;

1, 3;

1, 4;

1, 5;

1, 10;

1, 15;

1, 20;

1, 3;

2, 2;

3, 5;

2, 5;

3, 2;

5, or 3;

5.

7. The medical device of claim 1 wherein the coating comprised and about a 10:

1 ratio of the active agent to the binding agent, wherein the active agent comprises sirolimus wherein the binding agent comprises Polyarginine.

8. The medical device of claim 7, wherein the Polyarginine average molecular weight is 70 kDa or is 5-15 kDa.

9. The medical device of claim 1, wherein the balloon is an invertable balloon, and the coating is on an abluminal side of the invertable balloon.

10. The medical device of claim 1, wherein the coating is on an abluminal side of the balloon, and wherein the medical device further comprises a sheath over the balloon.

11. The medical device of claim 10, wherein the sheath is retractable once the coated balloon reaches the treatment site, is positioned near the treatment site, is positioned at the treatment site, is proximal to the treatment site, is distal to the treatment site, or is within the treatment site.

12. The medical device of claim 1, further comprising an occluder configured to block the flow of bodily fluids at a treatment site during exposure of the coating to the treatment site.

13. The medical device of claim 12, wherein the occluder comprises a second balloon that occludes the flow of the blood at the treatment site, or wherein the balloon has two sections, a first section comprising the occluder and a second section comprising the coating.

14. The medical device of claim 12, wherein a distal portion of the balloon is coated and wherein a proximal portion of the balloon is not coated, and wherein the proximal portion of the balloon is the occlude, or wherein a proximal portion of the balloon is coated and wherein a distal portion of the balloon is not coated, and wherein the distal portion of the balloon is the occluder.

15. The medical device of claim 1, wherein at least one of:

at most 1% of coating is removed from the balloon due to tracking of the coated balloon to the treatment site, at most 5% of coating is removed from the balloon due to tracking of the coated balloon to the treatment site, at most 10% of coating is removed from the balloon due to tracking of the coated balloon to the treatment site, at most 15% of coating is removed from the balloon due to tracking of the coated balloon to the treatment site, at most 20% of coating is removed from the balloon due to tracking of the coated balloon to the treatment site, at most 25% of coating is removed from the balloon due to tracking of the coated balloon to the treatment site, and at most 30% of coating is removed from the balloon due to tracking of the coated balloon to the treatment site.

16. A method comprising

providing a device comprising a balloon;

and a coating on at least a portion of the balloon, wherein the coating comprises a polymer, a macrolide immunosuppressive drug in crystalline form present on an exterior surface of the coating and a cationic binding agent, and

inflating the balloon of the device in an artery in vivo, wherein upon inflating the balloon at least 3% of the active agent is transferred to tissue of the artery in vivo.

17. The method of claim 16, wherein the binding agents comprises at least one of:

Polyarginine, Polyarginine 9-L-pArg, DEAE-Dextran (Diethylaminoethyl cellulose-Dextran), DMAB (Didodecyldimethylammonium bromide), PEI (Polyethyleneimine), TAB (Tetradodecylammonium bromide), and DMTAB (Dimethylditetradecylammonium bromide).

18. The method of claim 16 wherein the coating comprised and about a 10:

1 ratio of the active agent to the binding agent, wherein the active agent comprises sirolimus wherein the binding agent comprises Polyarginine.

19. A method of coating at least a portion of a medical device comprising a balloon, thereby forming on the medical device a coating on the balloon comprising an active agent and a cationic binding agent, wherein the method comprises:

a. dissolving the binding agent to form a binding agent solution,

b. combining the binding agent solution and the active agent,

c. mixing the combined binding agent and active agent using a high shear mixer,

d. forming a suspension comprising the combined mixed active agent and binding agent,

e. lyophilising the suspension to form a lyophilisate of the active agent and the binding agent, and

f. coating the balloon with the lyophilisate in powder form using an eSTAT process, wherein the active agent coated on the balloon comprises a macrolide immunosuppressive drug in crystalline form present on an exterior surface of the coating.

20. The method of claim 19 wherein the binding agents comprises at least one of:

Polyarginine, Polyarginine 9-L-pArg, DEAE-Dextran (Diethylaminoethyl cellulose-Dextran), DMAB (Didodecyldimethylammonium bromide), PEI (Polyethyleneimine), TAB (Tetradodecylammonium bromide), and DMTAB (Dimethylditetradecylammonium bromide).