Apparatus and methods for variably controlled substance delivery from implanted prostheses Number:7,077,859 from the United States Patent and Trademark Office (PTO) owispatent The present invention provides improved stents and other prostheses for delivering substances to vascular and other luminal and intracorporeal enviroments. In particular, the present invention provides luminal prostheses which allow for a programmed and controlled substance delivery protocols for a variety of purposes. The prostheses comprise a scaffold which is implantable within a body lumen and a substance reservoir present over at least a portion of the scaffold. Usually, a rate-controlling element will be formed over the substance-containing reservoir to provide for a number of different substance release characteristics.<H prostheses, controlled, Apparatus, and, m, 7077859.html, Patent, pto, 7077859

Title: Apparatus and methods for variably controlled substance delivery from implanted prostheses

Abstract: The present invention provides improved stents and other prostheses for delivering substances to vascular and other luminal and intracorporeal enviroments. In particular, the present invention provides luminal prostheses which allow for a programmed and controlled substance delivery protocols for a variety of purposes. The prostheses comprise a scaffold which is implantable within a body lumen and a substance reservoir present over at least a portion of the scaffold. Usually, a rate-controlling element will be formed over the substance-containing reservoir to provide for a number of different substance release characteristics.

Patent Number: 7,077,859 Issued on 07/18/2006 to Sirhan, et al.

Inventors: Sirhan; Motasim (Sunnyvale, CA); Yan; John (Los Gatos, CA)
Assignee: Avantec Vascular Corporation (Sunnyvale, CA)

Appl. No.: 017500

Filed: December 14, 2001

Related U.S. Patent Documents


Application Number	Filing Date	Patent Number	Issue Date
10002595	Nov., 2001
09783253	Feb., 2001
09782927	Feb., 2001	6471980
09783254	Feb., 2001
09782804	Feb., 2001
60308381	Jul., 2001
60258024	Dec., 2000

Current U.S. Class: 623/1.15 ; 623/1.42

Current International Class: A61F 2/06 (20060101)

Field of Search: 623/1.13,1.39,1.4-1.48

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Primary Examiner: McDermott; Corrine
Assistant Examiner: Phan; Hieu
Attorney, Agent or Firm: Townsend and Townsend and Crew LLP

Parent Case Text

CROSS-REFERENCES TO RELATED APPLICATIONS

This application is a continuation-in-part and claims the benefit of Non-Provisional U.S. patent application Ser. No. 10/002,595, filed Nov. 1, 2001. which claims the benefit of Provisional U.S. Patent Application 60/258,024, filed on Dec. 22, 2000; and is a continuation-in-part of U.S. patent applications Ser. Nos. 09/783,253, 09/782,927, now U.S. Pat No. 6,471,980, Ser. Nos. 09/783,254, and 09/782,804, all filed on Feb. 13. 2001; and which claims the benefit of Provisional U.S. Patent Application 60/308,381, filed on Jul. 26, 2001. Each of these applications is assigned to the assignee of the present application. The full disclosures of each of the above applications is incorporated herein by reference.

Claims

What is claimed is:

1. A device for intracorporeal use within a patient's body, comprising: an implantable scaffold; at least one source of at least one therapeutic capable agent having a degree of crystallinity less than about 90% and associated with the scaffold and configured to release the therapeutic capable agent within the patient's body; and a rate-controlling element disposed adjacent at least a portion of the source and being configured to control the release of the therapeutic capable agent to the patient's body.

2. A device as in claim 1 wherein the therapeutic capable agent has a degree of crystallinity less than about 50%.

3. A device as in claim 1 wherein the at least one source of at least one therapeutic capable agent has a degree of crystallinity less than about 50%.

4. A device as in claim 1 wherein the at least one source of at least one therapeutic capable agent as formed on the scaffold has a degree of crystallinity less than about 90%.

5. A device as in claim 1 wherein the at least one source of at least one therapeutic capable agent as formed on the scaffold has a degree of crystallinity less than about 50%.

6. A device as in claim 1 wherein the at least one therapeutic capable agent as formed on the scaffold has a degree of crystallinity less than about 90%.

7. A device as in claim 1 wherein the at least one therapeutic capable agent as formed on the scaffold has a degree of crystallinity less than about 50%.

8. A device as in claim 1 wherein the at least one therapeutic capable agent has a degree of crystallinity less than about 90%.

9. A device as in claim 1 wherein the at least one source comprises a matrix including the at least one therapeutic capable agent.

10. A device as in claim 1 wherein the at least one source comprises the at least one therapeutic capable agent.

11. A device for intracorporeal use within a patient's body, comprising: an implantable scaffold; at least one source of at least one therapeutic capable agent associated with the scaffold and configured to release the therapeutic capable agent at a targeted tissue site within the patient's body; and a rate-controlling element disposed adjacent at least a portion of the source and being configured to effectuate a therapeutic capable agent flux density of about 1.71.times.10-14 g/(cm.sup.2s) to about 1.71.times.10-8 g/(cm.sup.2s).

12. A device for as in claim 11 wherein the flux density ranges from about 1.71.times.10-14 g/(cm.sup.2s) to about 3.43.times.10-9 g/(cm.sup.2s).

13. A device for as in claim 11 wherein the flux density ranges from about 8.57.times.10-12 g/(cm.sup.2s) to about 3.43.times.10-9 g/(cm.sup.2s).

14. A device for as in claim 11 wherein the flux density ranges from about 1.71.times.10-11 g/(cm.sup.2s) to about 1.03.times.10-9 g/(cm.sup.2s).

15. A device as in claim 11 wherein the at least one source comprises a matrix including the at least one therapeutic capable agent.

16. A device as in claim 11 wherein the at least one source comprises the at least one therapeutic capable agent.

17. A device for intracorporeal use within a patient's body, comprising: an implantable scaffold; at least one source of at least one therapeutic capable agent associated with the scaffold and configured to release the therapeutic capable agent at a targeted tissue site within the patient's body; and a rate-controlling element disposed adjacent at least a portion of the source and being configured to control the release of the therapeutic capable agent in the patient's body, the device having a residual stress in an unexpanded state less than about 10%.

18. A device for as in claim 17 wherein the residual stress is less than about 5%.

19. A device for as in claim 17 wherein the residual stress is less than about 1%.

20. A device for as in claim 17 wherein the residual stress is less than about 0.5%.

21. A device as in claim 17 wherein the at least one source comprises a matrix including the at least one therapeutic capable agent.

22. A device as in claim 17 wherein the at least one source comprises the at least one therapeutic capable agent.

23. A device for intracorporeal use within a patient's body, comprising: an implantable scaffold; at lease one source of at least one therapeutic capable agent associated with the scaffold and configured to release the therapeutic capable agent within the patient's body; and a rate-controlling element layer covering at least a portion of the source and being formed from a non-porous material.

24. A device as in claim 23, wherein the non-porous material comprises parylene.

25. A device as in claim 23, wherein the nonporous material becomes at least partially porous when exposed to conditions in the patient's body.

26. A device as in claim 23, wherein the rate-controlling element becomes disrupted when exposed to conditions in the patient's body.

27. A device as in claim 23, wherein the rate-controlling element includes a therapeutic capable agent.

28. A device as in claim 27, wherein the therapeutic capable agent in the rate controlling element is the same as the therapeutic capable agent in the source.

29. A device as in claim 23, wherein the nonporous material is selected from the group consisting of plasma deposited polymers, sputtered materials, evaporated materials, electroplated metals, electroplated alloys, glow discharge coatings, polyethylenes, polyurethanes, silicone rubber, cellulose, and parylene.

30. A device as in claim 23 wherein the at least one source comprises a matrix including the at least one therapeutic capable agent.

31. A device as in claim 23 wherein the at least one source comprises the at least one therapeutic capable agent.

Description

BACKGROUND OF THE INVENTION

1. Field of the Invention

The present invention relates generally to medical devices and methods. More particularly, the present invention provides luminal prostheses, such as vascular stents and grafts for reducing or inhibiting restenosis.

The present invention relates generally to medical devices and methods. More particularly, the present invention provides luminal prostheses, such as vascular stents and grafts for reducing or inhibiting restenosis.

A number of percutaneous intravascular procedures have been developed for treating stenotic atherosclerotic regions of a patient's vasculature to restore adequate blood flow. The most successful of these treatments is percutaneous transluminal angioplasty (PTA). In PTA, a catheter, having an expandable distal end usually in the form of an inflatable balloon, is positioned in the blood vessel at the stenotic site. The expandable end is expanded to dilate the vessel to restore adequate blood flow beyond the diseased region. Other procedures for opening stenotic regions include directional arthrectomy, rotational arthrectomy, laser angioplasty, stenting, and the like. While these procedures have gained wide acceptance (either alone or in combination, particularly PTA in combination with stenting), they continue to suffer from significant disadvantages. A particularly common disadvantage with PTA and other known procedures for opening stenotic regions is the frequent occurrence of restenosis.

Restenosis refers to the re-narrowing of an artery after an initially successful angioplasty. Restenosis afflicts approximately up to 50% of all angioplasty patients and is the result of injury to the blood vessel wall during the lumen opening angioplasty procedure. In some patients, the injury initiates a repair response that is characterized by smooth muscle cell proliferation referred to as "hyperplasia" in the region traumatized by the angioplasty. This proliferation of smooth muscle cells re-narrows the lumen that was opened by the angioplasty within a few weeks to a few months, thereby necessitating a repeat PTA or other procedure to alleviate the restenosis.

A number of strategies have been proposed to treat hyperplasia and reduce restenosis. Previously proposed strategies include prolonged balloon inflation during angioplasty, treatment of the blood vessel with a heated balloon, treatment of the blood vessel with radiation following angioplasty, stenting of the region, and other procedures. While these proposals have enjoyed varying levels of success, no one of these procedures is proven to be entirely successful in substantially or completely avoiding all occurrences of restenosis and hyperplasia.

As an alternative or adjunctive to the above mentioned therapies, the administration of therapeutic agents following PTA for the inhibition of restenosis has also been proposed. Therapeutic treatments usually entail pushing or releasing a therapeutic capable agent through a catheter or from a stent. While holding great promise, the delivery of therapeutic agents for the inhibition of restenosis has not been entirely successful.

As an alternative or adjunctive to the above mentioned therapies, the administration of therapeutic agents following PTA for the inhibition of restenosis has also been proposed. Therapeutic treatments usually entail pushing or releasing a drug through a catheter or from a stent. While holding great promise, the delivery of therapeutic agents for the inhibition of restenosis has not been entirely successful.

Accordingly, it would be a significant advance to provide improved devices and methods for reducing, inhibiting, or treating restenosis and hyperplasia which may follow angioplasty and other interventional treatments. This invention satisfies at least some of these and other needs.

2. Description of the Background Art

Local drug delivery for the prevention of restenosis is described in Lincoff et al. (1994) Circulation 90:2070-2084. A full description of an exemplary luminal prosthesis for use in the present invention is described in co-pending application Ser. No. 09/565,560 filed May 4, 2000, the full disclosure of which is incorporated herein by reference. Method and apparatus for releasing active substances from implantable and other devices are described in U.S. Pat. Nos. 6,096,070; 5,824,049; 5,624,411; 5,609,629; 5,569,463; 5,447,724; and 5,464,650. The use of stents for drug delivery within the vasculature are described in PCT Publication No. WO 01/01957 and U.S. Pat. Nos. 6,099,561; 6,071,305; 6,063,101; 5,997,468; 5,980,551; 5,980,566; 5,972,027; 5,968,092; 5,951,586; 5,893,840; 5,891,108; 5,851,231; 5,843,172; 5,837,008; 5,769,883; 5,735,811; 5,700,286; 5,679,400; 5,649,977; 5,637,113; 5,591,227; 5,551,954; 5,545,208; 5,500,013; 5,464,450; 5,419,760; 5,411,550; 5,342,348; 5,286,254; and 5,163,952. Biodegradable materials are described in U.S. Pat. Nos. 6,051,276; 5,879,808; 5,876,452; 5,656,297; 5,543,158; 5,484,584; 5,176,907; 4,894,231; 4,897,268; 4,883,666; 4,832,686; and 3,976,071. The use of hydrocylosiloxane as a rate limiting barrier is described in U.S. Pat. No. 5,463,010. Methods for coating of stents is described in U.S. Pat. No. 5,356,433. Coatings to enhance biocompatibility of implantable devices are described in U.S. Pat. Nos. 5,463,010; 5,112,457; and 5,067,491. Porous and non-porous materials for drug delivery, coating, and other uses are described in U.S. Pat. Nos. 5,488,015; 5,470,802; 5,428,123; 5,288,504; 5,270,047; 5,243,756; 5,130,889; 4,788,063; 3,993,072; and 3,854,480. Energy-based devices are described in U.S. Pat. Nos. 6,031,375; 5,928,145; 5,735,811; 5,728,062; 5,725,494; 5,409,000, 5,368,557; 5,000,185; and 4,936,281. Magnetic processes, some of which have been used in drug delivery systems, are described in U.S. Pat. Nos. 5,427,767; 5,225,282; 5,206,159; 5,069,216; 4,904,479; 4,871,716; 4,501,726; 4,357,259; 4,345,588; and 4,335,094.

The disclosure of this application is related to the disclosures of the following applications: Ser. No. 09/782,927, now U.S. Pat. No. 6,471,980; Ser. No. 09/783,254; and Ser. No. 09/782,804.

The full disclosures of each of the above references are incorporated herein by reference.

BRIEF SUMMARY OF THE INVENTION

The present invention is directed to improved devices for preparation or treatment of susceptible tissue sites, and methods making and using the same. In particular, the present invention is directed to corporeal, more particularly intracorporeal devices. In one embodiment, the present devices and methods reduce the formation or progression of restenosis and/or hyperplasia which may follow an intravascular intervention. In an embodiment, the device provides a therapeutic capable agent to the susceptible tissue site. Preferably, the therapeutic capable agent is provided to the therapeutic capable agent in a manner as to become available, immediately or after a delay period, to the susceptible tissue site upon introduction of the device to the corporeal body.

As used herein, "susceptible tissue site" refers to a tissue site that is injured, or may become injured as a result of an impairment (e.g., disease, medical condition), or may become injured during or following an interventional procedure such as an intravascular intervention. The term "intravascular intervention" includes a variety of corrective procedures that may be performed to at least partially resolve a stenotic, restenotic, or thrombotic condition in a blood vessel, usually an artery, such as a coronary artery. Usually, the corrective procedure will comprise balloon angioplasty. The corrective procedure may also comprise directional atherectomy, rotational atherectomy, laser angioplasty, stenting, or the like, where the lumen of the treated blood vessel is enlarged to at least partially alleviate a stenotic condition which existed prior to the treatment. The susceptible tissue site may include tissues associated with intracorporeal lumens, organs, or localized tumors. As used herein, the term "intracorporeal body" refers to body lumens or internal corporeal tissues and/or organs, within a corporeal body. The body lumen may be any blood vessel in the patient's vasculature, including veins, arteries, aorta, and particularly including coronary and peripheral arteries, as well as previously implanted grafts, shunts, fistulas, and the like. It will be appreciated that the present invention may also be applied to other body lumens, such as the biliary duct, which are subject to excessive neoplastic cell growth. Examples of internal corporeal tissues and organs, include various organs, nerves, glands, ducts, and the like. In an embodiment, the device includes luminal prostheses such as vascular stents or grafts. In another embodiment, the device may include, cardiac pacemaker leads or lead tips, cardiac defibrillator leads or lead tips, heart valves, sutures, or needles, pacemakers, orthopedic devices, appliances, implants or replacements, or portions of any of the above.

As used herein the term "therapeutic capable agent" includes at least one compound which is either therapeutic as it is introduced to the corporeal body (e.g., human subject) under treatment, or becomes therapeutic after entering the corporeal body of the subject (or exposed to the surface of the corporeal body as the case may be), by for example, reaction with a native or non-native substance or condition. Examples of native conditions include pH (e.g. acidity), chemicals, temperature, salinity, conductivity, contractile or expansive changes of the body lumen/organ, and pulsating nature of the body fluids as they flow through or come in contact with the device; with non-native conditions including those such as magnetic fields, and ultrasound. In the present application, the chemical name of any of the therapeutic capable agents or other compounds is used to refer to the compound itself and to pro-drugs (precursor substances that are converted into an active form of the compound in the body), and/or pharmaceutical derivatives, analogues, or metabolites thereof (bioactive compound to which the compound converts within the body directly or upon introduction of other agents or conditions (e.g., enzymatic, chemical, energy), or environment (e.g., pH)).

In an embodiment, the device comprises a structure and at least one source of at least one therapeutic capable agent associated with the structure. In one embodiment, the device further comprises a rate-controlling element disposed or formed adjacent at least a portion of the structure. The therapeutic capable agent is associated at least in part with either or both the structure and the rate-controlling element in a manner as to become available, immediately or after a delay period, to the susceptible tissue site upon introduction of the device to the corporeal body. As used herein the term "associated with" refers to any form of association such as directly or indirectly being coupled to, connected to, disposed on, disposed within, attached to, adhered to, bonded to, adjacent to, entrapped in, and like configurations.

In an embodiment, the device is implantable within a corporeal body including an intracorporeal target site (e.g., body organs or lumens). The intracorporeal target site may include the susceptible tissue site or in the alternative it may be a supply site such as an artery which supplies blood to the susceptible tissue site.

In one embodiment the structure may be an expandable structure. In another embodiment, the structure may have a substantially constant size or diameter, or alternatively depending on the application and use, may be a contractable structure. The expandable structure may be in the form of a stent, which additionally maintains luminal patency, or in the form of a graft, which additionally protects or enhances the strength of a luminal wall. The device, may comprise at least in part, a scaffold, preferably formed at least in part from an open lattice. Optionally, the scaffold comprises an at least substantially closed surface. The expandable structure may be radially expandable. The structure may be self-expanding or expandable by another object such as a balloon. In an embodiment, the structure includes at least one surface, usually, a tissue facing surface. In another embodiment, the structure includes a tissue facing surface, another surface usually a luminal surface, and two edge surfaces. In an embodiment, the structure may have an interior disposed between two surfaces, usually, the tissue facing and the luminal surfaces. In an embodiment, the structure includes portions having different mechanical stress or strain profiles upon expansion or contraction, or areas which are substantially in the direct line of fluid (e.g., blood or other bodily fluids) flow through the body. By way of example, the different portions of the structure may exhibit different stress characteristics during expansion of the device when implanted within the intracorporeal body. In one embodiment, the structure includes portions having relatively lower and portions having relatively higher mechanical stress or strain profiles with respect to one another. The term "having different mechanical profile" will herein be used to refer to this characteristic of the structure or prosthesis. In an embodiment, when the device may include an axially different coating profile such that the prosthesis comprises a different profile of the therapeutic capable agent and/or the rate-controlling element which will be in the direct flow of the body fluids thus subject to more turbulent flow.

The source may be disposed or formed adjacent at least a portion of the structure. The source may be disposed or formed adjacent at least a portion of either or both surfaces of the expandable structure, within the interior of the structure disposed between the two surfaces, adjacent either or both the edges, or any combination thereof. The association of the therapeutic capable agent with either or both the structure and the rate-controlling element may be continuous or in discrete segments. In one embodiment, the source is disposed or formed adjacent only a portion of the structure and/or the rate-controlling element, preferably, areas having lower mechanical stress profiles.

The expandable structure may be formed of any suitable material such as metals, polymers, or a combination thereof. In one embodiment, the expandable structure may be formed of an at least partially biodegradable material, selected from the group consisting of polymeric material, metal