Drug delivery medical device

• US 9,981,071 B2
• Filed: 10/04/2016
• Issued: 05/29/2018
• Est. Priority Date: 07/17/2008
• Status: Active Grant

• Current Assignee: Micell Medtech Incorporated
• Original Assignee: Micell Technologies Inc.
• Inventors: McClain, James B., Taylor, Charles Douglas, Neet, John
• Primary Examiner(s): Azpuru, Carlos A
• Assistant Examiner(s): HAGOPIAN, CASEY SHEA
• Application Number:
  US15/284,677
• Publication Number:
  US 20170136155A1
• Time in Patent Office: 602 Days
• Field of Search: None
• CPC Class Codes: A61F 2002/30535 Special structural features of bone or joint prostheses not otherwise provided for
• CPC Class Codes: A61F 2250/0058 Additional features; Implant or prostheses properties not otherwise provided for
• CPC Class Codes: A61K 31/20 having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids
• CPC Class Codes: A61K 31/7088 Compounds having three or more nucleosides or nucleotides
• CPC Class Codes: A61K 31/7105 Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links
• CPC Class Codes: A61K 31/715 Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61K 9/0024 Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue compositions for intravenous administration, normal injectable solutions or dispersions for, e.g. subcutaneous administration A61K9/0019; brain implants A61K9/0085; (coated) prostheses, catheters or stents A61L
• CPC Class Codes: A61K 9/0034 Urogenital system, e.g. vagina, uterus, cervix, penis, scrotum, urethra, bladder; Personal lubricants
• CPC Class Codes: A61L 17/005 containing a biologically active substance, e.g. a medicament or a biocide
• CPC Class Codes: A61L 17/145 Coating
• CPC Class Codes: A61L 2300/406 Antibiotics
• 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 2300/426 Immunomodulating agents, i.e. cytokines, interleukins, interferons
• CPC Class Codes: A61L 2300/602 Type of release, e.g. controlled, sustained, slow
• CPC Class Codes: A61L 2300/608 having two or more layers
• CPC Class Codes: A61L 2300/63 Crystals
• CPC Class Codes: A61L 2420/08 Coatings comprising two or more layers
• CPC Class Codes: A61L 27/34 Macromolecular materials
• CPC Class Codes: A61L 27/50 Materials characterised by their function or physical properties , e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
• CPC Class Codes: A61L 27/54 : Biologically active materials, e.g. therapeutic substances A61L27/227 takes precedence
• CPC Class Codes: A61L 29/08 : Materials for coatings
• CPC Class Codes: A61L 29/085 : Macromolecular materials
• CPC Class Codes: A61L 29/14 : Materials characterised by their function or physical properties , e.g. lubricating compositions
• 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: A61L 31/08 : Materials for coatings
• CPC Class Codes: A61L 31/10 : Macromolecular materials
• CPC Class Codes: A61L 31/14 : Materials characterised by their function or physical properties , e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
• CPC Class Codes: A61L 31/16 : Biologically active materials, e.g. therapeutic substances A61L31/047 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

Abstract

Provided is a coated implantable medical device, comprising: a substrate; and a coating disposed on said substrate, wherein said 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 said coating and on said substrate until the implantable device is deployed at an intervention site inside the body of a subject and wherein upon deployment of said medical device in the body of said subject a portion of said pharmaceutical agent and/or active biological agent is delivered at said intervention site along with at least a portion of said polymer and/or a at least a portion of said pharmaceutical carrying agents.

Claims

1. A method comprising the steps of:

stimulating a substrate for 20 seconds or less to release at least about 35% of a coating on at least a portion of the substrate, the coating including a polymer and a crystalline pharmaceutical agent.

2. The method of claim 1, wherein the substrate is a balloon.

3. The method of claim 2, wherein the stimulation step includes inflating the balloon.

4. The method of claim 1, wherein the pharmaceutical agent and the polymer are in the same layer, in separate layers, or form overlapping layers.

5. The method of claim 1, wherein the coating includes a plurality of layers.

6. The method of claim 5, wherein the plurality of layers comprise three layers deposited as follows:

a first polymer layer,

a first pharmaceutical agent layer, and

a second polymer layer.

7. The method of claim 1, wherein the polymer is selected from the group consisting of non-absorbable and bioabsorbable polymer.

8. The method of claim 7, wherein the wherein the bioabsorbable polymer includes between 1% and 95% glycolic acid content PLGA-based polymer.

9. The method of claim 7, wherein the bioabsorbable polymer is selected from the group consisting of:

Polylactides (PLA);

PLGA (poly(lactide-co-glycolide);

Polyanhydrides;

Polyorthoesters;

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

DLPLA—

poly(dl-lactide);

LPLA—

poly(l-lactide);

PGA—

polyglycolide;

PDQ—

poly(dioxanone);

PGA-TMC—

poly(glycolide-co-trimethylene carbonate);

PGA-LPLA—

poly(l-lactide-co-glycolide);

PGA-DLPLA—

poly(dl-lactide-co-glycolide);

LPLA-DLPLA—

poly(l-lactide-co-dl-lactide); and

PDO-PGA-TMC—

poly(glycolide-co-trimethylene carbonate-co-dioxanone), and combinations, copolymers, and derivatives thereof.

10. The method of claim 1, wherein the pharmaceutical agent comprises a macrolide immunosuppressive drug.

11. The method of claim 10, wherein the macrolide immunosuppressive drug comprises one or more of rapamycin, 40-O-(2-Hydroxyethyl)rapamycin (everolimus), 40-O-Benzyl-rapamycin, 40-O-(4′

-Hydroxymethyl)benzyl-rapamycin, 40-O-[4′

-(1,2-Dihydroxyethyl)]benzyl-rapamycin, 40-O-Allyl-rapamycin, 40-O-[3′

-(2,2-Dimethyl-1,3-dioxolan-4(S)-yl)-prop-2′

-en-1′

-yl]-rapamycin, (2′

;

E,4′

S)-40-O-(4′

,5′

-Dihydroxypent-2′

-en-1′

-yl)-rapamycin 40-O-(2-Hydroxy)ethoxycar-bonylmethyl-rapamycin, 40-O-(3-Hydroxy)propyl-rapamycin, 40-O-(6-Hydroxy)hexyl-rapamycin, 40-O-[2-(2-Hydroxy)ethoxy]ethyl-rapamycin, 40-O-[(3S)-2,2-Dimethyldioxolan-3-yl]methyl-rapamycin, 40-O-[(2S)-2,3-Dihydroxyprop-1-yl]-rapamycin, 40-O-(2-Acetoxy)ethyl-rapamycin, 40-0-(2-Nicotinoyloxy)ethyl-rapamycin, 40-O-[2-(N-Morpholino)acetoxy]ethyl-rapamycin, 40-O-(2-N-Imidazolylacetoxy)ethyl-rapamycin, 40-O-[2-(N-Methyl-N′

-piperazinyl)acetoxy]ethyl-rapamycin, 39-O-Desmethyl-39,40-O,O-ethylene-rapamycin, (26R)-26-Dihydro-40-O-(2-hydroxy)ethyl-rapamycin, 28-O-Methyl-rapamycin, 40-O-(2-Aminoethyl)-rapamycin, 40-O-(2-Acetaminoethyl)-rapamycin, 40-O-(2-Nicotinamidoethyl)-rapamycin, 40-O-(2-(N-Methyl-imidazo-2′

-ylcarbethoxamido)ethyl)-rapamycin, 40-O-(2-Ethoxycarbonylaminoethyl)-rapamycin, 40-O-(2-Tolylsulfonamidoethyl)-rapamycin, 40-O-[2-(4′

,5′

-Dicarboethoxy-1′

,2′

,3′

-triazol-1′

-yl)-ethyl]-rapamycin, 42-Epi-(tetrazolyl)rapamycin (tacrolimus), and 42-[3-hydroxy-2-(hydroxymethyl)-2-methylpropanoate]rapamycin (temsirolimus).

12. The method of claim 1, wherein the pharmaceutical agent is rapamycin.

13. The method of claim 1, wherein the pharmaceutical agent is at least 50% crystalline.

14. The method of claim 1, wherein the pharmaceutical agent is at least 90% crystalline.

15. The method of claim 1, wherein the coating is formed on said substrate by a process comprising at least one of:

depositing a polymer by an e-RESS, an e-SEDS, or an e-DPC process, and depositing the pharmaceutical agent by an e-RESS, an e-SEDS, or an e-DPC process.

16. The device of claim 15, wherein the process of forming the coating provides improves adherence of the coating to the substrate prior to deployment of the device and facilitates dissociation of said coating from said substrate upon stimulation.

17. The device of claim 1, wherein the device is adapted to transfer less than about 10% of the coating absent stimulation of the coating.

18. A method comprising the steps of:

inflating a balloon for 20 seconds or less to release at least about 35% of a coating on at least a portion of the balloon, the coating including a bioabsorbable polymer and a crystalline pharmaceutical agent.

19. The method of claim 18, wherein the bioabsobable polymer is PLGA and the pharmaceutical agent is rapamycin.

20. The method of claim 19, wherein the coating includes three layers deposited as follows:

a first PLGA layer,

a first rapamycin layer, and

a second PLGA layer.

21. A method comprising the steps of:

providing a balloon having a coating including three polymer layers and two crystalline pharmaceutical agent layers; and

inflating the balloon for at most 19seconds to release at least about 35% of the coating.