Drug delivery medical device

• US 10,188,772 B2
• Filed: 10/18/2013
• Issued: 01/29/2019
• Est. Priority Date: 10/18/2011
• Status: Active Grant

• Current Assignee: Micell Medtech Incorporated
• Original Assignee: Micell Technologies Inc.
• Inventors: McClain, James B., Taylor, Charles Douglas, Fagan, Meagan M.
• Primary Examiner(s): Coniglio, Audrea B
• Application Number:
  US14/437,097
• Publication Number:
  US 20150250926A1
• Time in Patent Office: 1,929 Days
• CPC Class Codes: A61L 2300/416 Anti-neoplastic or anti-proliferative or anti-restenosis or anti-angiogenic agents, e.g. paclitaxel, sirolimus
• CPC Class Codes: A61L 2300/622 Microcapsules
• CPC Class Codes: A61L 2300/624 Nanocapsules
• CPC Class Codes: A61L 2300/63 Crystals
• CPC Class Codes: A61L 29/085 Macromolecular materials
• CPC Class Codes: A61L 29/148 Materials at least partially resorbable by the body
• CPC Class Codes: A61L 29/16 Biologically active materials, e.g. therapeutic substances A61L29/048 takes precedence
• CPC Class Codes: A61M 2025/105 having a balloon suitable for drug delivery, e.g. by using holes for delivery, drug coating or membranes
• CPC Class Codes: C08L 29/04 Polyvinyl alcohol; Partially hydrolysed homopolymers or copolymers of esters of unsaturated alcohols with saturated carboxylic acids
• CPC Class Codes: C08L 67/04 Polyesters derived from hydroxycarboxylic acids, e.g. lactones C08L67/06 takes precedence

Abstract

A medical device that releases a pharmaceutical agent to a target site is disclosed. The medical device includes a balloon, and a coating on at least a portion of the balloon. The coating includes particles of a pharmaceutical agent. Each particle of the particles of the pharmaceutical agent is at least partially encapsulated in a polymer material. A method of releasing a pharmaceutical agent at a target site is also disclosed. The method includes the steps of providing a device including a balloon, and a coating on at least a portion of the balloon, the coating including particles of a pharmaceutical agent, and each particle of the pharmaceutical agent is at least partially encapsulated in a polymer material; positioning the device to allow the balloon to reach the target site; and inflating the balloon of the device.

Claims

1. A medical device comprising:

a balloon; and

a coating on at least a portion of the balloon,

wherein the coating comprises smooth and spherical particles having rapamycin particles encapsulated in a first polymer material prior to inclusion in the coating, the particles being from about 0.5 μ

m to about 10 μ

m in size and the first polymer being PLGA, and

wherein each particle is at least partially encapsulated in a second polymer material in the coating.

2. The medical device of claim 1, wherein at least 50% of the surface area of certain of the particles is encapsulated in the second polymer material.

3. The medical device of claim 1, wherein at least 75% of the surface area of certain of the particles is encapsulated in the second polymer material.

4. The medical device of claim 1, wherein at least 90% of the surface area of certain of the particles is encapsulated in the second polymer material.

5. The medical device of claim 1, wherein at least 95% of the surface area of certain of the particles is encapsulated in the second polymer material.

6. The medical device of claim 1, wherein the coating has an average thickness of from 2 microns to 20 microns.

7. The medical device of claim 1, wherein the pharmaceutical agent has a crystallinity of from 25% to 95%.

8. The medical device of claim 1, wherein a weight ratio of the pharmaceutical agent and the second polymer material is from 40:

60 to 60;

40.

9. The medical device of claim 1, wherein the particles are at least partially encapsulated in the second polymer material by spray-drying a mixture of the pharmaceutical agent, the polymer material, and a solvent.

10. The medical device of claim 9, wherein the mixture is a solution and the solvent is a polar aprotic solvent.

11. The medical device of claim 9, wherein the mixture is a slurry and the solvent is water.

12. The medical device of claim 1, wherein the particles are at least partially encapsulated in the first polymer material by adding particles of the first polymer material to the pharmaceutical agent in a tumbling vessel.

13. The medical device of claim 12, wherein the particles of the first polymer material have an average particle size of from 10 microns to 100 microns.

14. The medical device of claim 12, wherein the particles of the first polymer material are added at a rate of from 100 μ

g to 1000 μ

g per minute.

15. The medical device of claim 1 wherein the particles are at least partially encapsulated in the first polymer material by forming an emulsion-based mixture comprising the pharmaceutical agent and the polymer material, and separating the polymer-encapsulated pharmaceutical agent from the emulsion-based mixture.

16. The medical device of claim 1, wherein the second polymer material comprises a bioabsorbable polymer.

17. The medical device of claim 16, wherein the bioabsorbable polymer is selected from the group consisting of polylactides (PLA);

poly(lactide-co-glycolide) (PLGA);

polyanhydrides;

polyorthoesters;

poly(N-(2-hydroxypropyl) methacrylamide);

poly(dl-lactide) (DLPLA);

poly(l-lactide) (LPLA);

polyglycolide (PGA);

poly(dioxanone) (PDO);

poly(glycolide-co-trimethylene carbonate) (PGA-TMC);

poly(l-lactide-co-glycolide) (PGA-LPLA);

poly(dl-lactide-co-glycolide) (PGA-DLPLA);

poly(l-lactide-co-dl-lactide) (LPLA-DLPLA);

poly(glycolide-co-trimethylene carbonate-co-dioxanone) (PDO-PGA-TMC), polyvinyl alcohol (PVA), polyarginine, and mixtures or co-polymers thereof.

18. The medical device of claim 17, wherein the bioabsorbable polymer is selected from the group consisting of PLGA, PVA, polyarginine, and mixtures thereof.

19. The medical device of claim 1, further comprising a binding agent deposited on an exterior surface of the encapsulated particles.

20. The medical device of claim 19, wherein a weight ratio between the binding agent and the second polymer material is from 1:

99 to 25;

75.

21. The medical device of claim 19, wherein the binding agent is deposited by spraying and drying a solution of the binging agent on the encapsulated particles of the pharmaceutical agent.

22. The medical device of claim 21, wherein the solution comprises the binding agent and water.

23. The medical device of claim 19, wherein the binding agent 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).

24. The medical device of claim 19, wherein the binding agent is polyarginine.

25. The medical device of claim 24, wherein the polyarginine has an average molecular weight of about 70 kDa.

26. The medical device of claim 24, wherein the polyarginine has an average molecular weight of 5-15 kDa.

27. The medical device of claim 1 wherein the encapsulated particles of the pharmaceutical agent are deposited on the balloon using an eSTAT coating process.

28. The medical device of claim 1, wherein the device releases at least 3% of the pharmaceutical agent upon inflation of the balloon.

38. The medical device of claim 1, wherein the first and second polymer materials are different.

39. The medical device of claim 1, wherein the first and second polymer materials are the same.

29. A method of releasing a pharmaceutical agent at a target site, comprising

providing a device comprising a balloon, and a coating on at least a portion of the balloon, wherein the coating comprises smooth and spherical particles having rapamycin particles encapsulated in a first polymer prior to inclusion in the coating, the particles being from about 0.5 μ

m to about 10 μ

m in size and the first polymer being PLGA, and wherein each particle is at least partially encapsulated in a second polymer material in the coating;

positioning the device to allow the balloon to reach the target site; and

inflating the balloon of the device,

wherein at least some of the pharmaceutical agent is released to the target site upon inflating the balloon.

30. The method of claim 29, wherein at least 3% of the pharmaceutical agent is released to the blood vessel upon inflation of the balloon.

31. The method of claim 29, wherein the second polymer material comprises a biodegradable polymer.

32. The method of claim 31 wherein the bioabsorbable polymer is selected from the group consisting of polylactides (PLA);

poly(lactide-co-glycolide) (PLGA);

polyanhydrides;

polyorthoesters;

poly(N-(2-hydroxypropyl) methacrylamide);

poly(dl-lactide) (DLPLA);

poly(l-lactide) (LPLA);

polyglycolide (PGA);

poly(dioxanone) (PDO);

poly(glycolide-co-trimethylene carbonate) (PGA-TMC);

poly(l-lactide-co-glycolide) (PGA-LPLA);

poly(dl-lactide-co-glycolide) (PGA-DLPLA);

poly(l-lactide-co-dl-lactide) (LPLA-DLPLA);

poly(glycolide-co-trimethylene carbonate-co-dioxanone) (PDO-PGA-TMC), polyvinyl alcohol (PVA), and mixtures or co-polymers thereof.

33. The method of claim 29, wherein the device further comprises a binding agent deposited on an exterior surface of the encapsulated particles of the pharmaceutical agent.

34. The method of claim 33, 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).

35. The method of claim 29, wherein the encapsulated particles of the pharmaceutical agent are deposited on the balloon using an eSTAT coating process.

36. A method of forming polymer-encapsulated crystalline rapamycin, the method comprising:

forming the emulsion-based mixture comprising the pharmaceutical agent and the polymer material;

evaporating a portion of the emulsion-based mixture, and filtering the remaining emulsion-based mixture.

37. The method claim 36, further comprising resuspending and lyophilizing the encapsulated pharmaceutical agent.