US5605696A
Expired / Lapsed
US
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Drug loaded polymeric material and method of manufacture
Assignee: Abbott Cardiovascular Systems Inc
•
Filing: 1995-03-30
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Granted: 1997-02-25
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Expires: 2015-03-30
Abstract
Abstract The drug loaded polymeric material containing a therapeutic drug can be applied to a structure of an intravascular stent. A therapeutically effective amount of a therapeutic drug is incorporated into such a layer of polymeric material, without significantly increasing the thickness of the stent, to avoid interfering with the function of the stent. The drug loaded polymer coating of the stent can formed to include pores, can be multi-layered to permit the combination of a plurality of different drug containing materials in a single stent, and can include a rate controlling membrane to allow for controlled retention and delivery of selected drugs within the affected blood vessel upon implantation. The layer of polymeric material is manufactured by combining the selected polymeric material with a relatively high loading of the therapeutic drug in a thermal process, such as coextrusion of the therapeutic drug with the polymeric material. The therapeutic drug is dispersed and incorporated into the polymer as small particles, preferably having a maximum cross-sectional dimension of 10 microns.
Inventors
- 👤 Robert P. Eury
- 👤 Darlene Garguilo
- 👤 Plaridel Villareal
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-23 15:34
CPC Classifications
A; A61; A61L; A61L31/00; A61L31/14; A61L31/16; A61L31/08; A61L31/10; A61L31/146; A61P; A61P3/00; A61P3/08; A61P43/00; A61P7/00; A61P7/02; A61P9/00; A61L2300/00; A61L2300/60; A61L2300/602; A61L2300/606; A61L2300/62; A61L2300/622; A61M; A61M25/00; A61M25/0043; A61M2025/0057
Claims Analysis
Total Claims: 43
Claim 1
Independent Claim
124 words
A method of incorporating a therapeutically effective amount of a therapeutic drug into a polymeric material for application to an intravascular stent, the method comprising the steps of: forming solid particles of a therapeutic drug to have a maximum cross-sectional dimension of about 10 microns; uniformly dispersing said solid particles of said therapeutic drug in said polymeric material such that said particles of said therapeutic drug form up to 70% by weight of the total weight of the therapeutic drug and the polymeric material; and uniformly dispersing a porosigen in said polymeric material together with said therapeutic drug, said porosigen being selected from the group consisting of sodium chloride, lactose, sodium heparin, polyethylene glycol, copolymers of polyethylene oxide and polypropylene oxide, and mixtures thereof.
Claim 2
Independent Claim
124 words
A method of incorporating a therapeutically effective amount of a therapeutic drug into a polymeric material for application to an intravascular stent, the method comprising the steps of: forming solid particles of a therapeutic drug to have a maximum cross-sectional dimension of about 10 microns; uniformly dispersing said solid particles of said therapeutic drug in said polymeric material such that said particles of said therapeutic drug form up to 70% by weight of the total weight of the therapeutic drug and the polymeric material; and uniformly dispersing a porosigen in said polymeric material together with said therapeutic drug, said porosigen being selected from the group consisting of sodium chloride, lactose, sodium heparin, polyethylene glycol, copolymers of polyethylene oxide and polypropylene oxide, and mixtures thereof.
Claim 3
Dependent Claim
24 words
The method of claim 1, wherein said step of forming solid particles of said therapeutic drug comprises air milling crystals of said therapeutic drug.
Claim 4
Dependent Claim
23 words
The method of claim 1, wherein said step of forming solid particles of said therapeutic drug comprises recrystallizing crystals of said therapeutic drug.
Claim 5
Dependent Claim
24 words
The method of claim 1, wherein said step of forming solid particles of said therapeutic drug comprises ball milling crystals of said therapeutic drug.
Claim 6
Dependent Claim
23 words
The method of claim 1, wherein said step of forming solid particles of said therapeutic drug comprises grinding crystals of said therapeutic drug.
Claim 7
Dependent Claim
81 words
The method of claim 1, wherein said therapeutic drug is selected from the group consisting of heparin, D-phe-pro-arg-chloromethylketone, dipyridamole, hirudin, recombinant hirudin, thrombin inhibitor, angiopeptin, angiotensin converting enzyme inhibitors, calcium channel blockers, colchicine, fibroblast growth factor antagonists, fish oil, omega 3-fatty acid, low molecular weight heparin, histamine antagonists, inhibitors of HMG-CoA reductase, methotrexate, monoclonal antibodies, nitroprusside, phosphodiesterase inhibitors, prostacyclin and prostacyclin analogues, prostaglandin inhibitor, PDGF antagonists, serotonin blockers, steroids, thioprotease inhibitors, triazolopyrimidine, alpha-interferon, and genetically engineered epithelial cells, and mixtures thereof.
Claim 8
Dependent Claim
16 words
The method of claim 1, wherein said polymeric material has a relatively low thermal processing temperature.
Claim 9
Dependent Claim
21 words
The method of claim 1, wherein said polymeric material has a thermal processing temperature of not more than approximately 100° C.
Claim 10
Dependent Claim
38 words
The method of claim 1, wherein said polymeric material is selected from the group consisting of polycaprolactone, poly(ethylene-co-vinyl acetate), poly(vinyl acetate), silicone gum rubber, poly-DL-lactic acid (DL-PLA), poly-L-lactic acid (L-PLA), polyorthoesters, polyiminocarbonates, aliphatic polycarbonates, polyphosphazenes, and mixtures thereof.
Claim 11
Dependent Claim
30 words
The method of claim 1, wherein said particles of said therapeutic drug comprise up to 70% by weight of the total weight of the therapeutic drug and the polymeric material.
Claim 12
Dependent Claim
34 words
The method of claim 1, wherein said step of uniformly dispersing said solid particles of said therapeutic drug in said polymeric material comprises coextruding said particles of said therapeutic drug and said polymeric material.
Claim 13
Dependent Claim
35 words
The method of claim 1, wherein said step of uniformly dispersing said solid particles of said therapeutic drug in said polymeric material comprises calendaring said particles of said therapeutic drug and said polymeric material together.
Claim 14
Dependent Claim
36 words
The method of claim 1, wherein said step of uniformly dispersing said solid particles of said therapeutic drug in said polymeric material comprises solvent casting said particles of said therapeutic drug together with said polymeric material.
Claim 15
Dependent Claim
35 words
The method of claim 1, wherein said step of uniformly dispersing a porosigen in said polymeric material together with said therapeutic drug comprises coextruding said porosigen together with said therapeutic drug and said polymeric material.
Claim 16
Dependent Claim
24 words
The method of claim 1, further including the step of dissolving said porosigen in said polymeric material to leave pores in said polymeric material.
Claim 17
Dependent Claim
17 words
The method of claim 15, wherein said pores have a maximum cross-sectional dimension of about 10 microns.
Claim 18
Dependent Claim
17 words
The method of claim 15, wherein said pores have a maximum cross-sectional dimension of about one micron.
Claim 19
Dependent Claim
31 words
The method of claim 1, further including the step of applying a rate-controlling membrane over said polymeric material to control the release rate of said therapeutic drug from said polymeric material.
Claim 20
Dependent Claim
34 words
The method of claim 18, wherein said step of applying a rate-controlling membrane over said polymeric material comprises forming said rate-controlling membrane to include a uniform dispersion of a porosigen in said rate-controlling membrane.
Claim 21
Dependent Claim
24 words
The method of claim 19, further including the step of dissolving said porosigen in said rate-controlling membrane to leave pores in said rate-controlling membrane.
Claim 22
Dependent Claim
33 words
The method of claim 19, wherein said porosigen in said rate-controlling membrane is selected from the group consisting of sodium chloride, lactose, sodium heparin, polyethylene glycol, polyethylene oxide/polypropylene oxide copolymers, and mixtures thereof.
Claim 23
Dependent Claim
27 words
The method of claim 1, further including the step of forming said polymeric material containing said therapeutic drug as a sheet at least about 25 microns thick.
Claim 24
Dependent Claim
25 words
The method of claim 22, further including the step of laminating said sheet of polymeric material containing said therapeutic drug to an intravascular stent structure.
Claim 25
Dependent Claim
20 words
The method of claim 23, further including the step of removing excess polymeric material laminated to said intravascular stent structure.
Claim 26
Dependent Claim
91 words
A polymeric material containing a therapeutic drug for application to an intravascular stent for carrying and delivering said therapeutic drug within a blood vessel in which said intravascular stent is placed, comprising: a polymeric material having a thermal processing temperature no greater than about 100° C; particles of a therapeutic drug incorporated in said polymeric material; and a porosigen uniformly dispersed in said polymeric material, said porosigen being selected from the group consisting of sodium chloride, lactose, sodium heparin, polyethylene glycol, copolymers of polyethylene oxide and polypropylene oxide, and mixtures thereof.
Claim 27
Dependent Claim
91 words
A polymeric material containing a therapeutic drug for application to an intravascular stent for carrying and delivering said therapeutic drug within a blood vessel in which said intravascular stent is placed, comprising: a polymeric material having a thermal processing temperature no greater than about 100° C; particles of a therapeutic drug incorporated in said polymeric material; and a porosigen uniformly dispersed in said polymeric material, said porosigen being selected from the group consisting of sodium chloride, lactose, sodium heparin, polyethylene glycol, copolymers of polyethylene oxide and polypropylene oxide, and mixtures thereof.
Claim 28
Dependent Claim
39 words
The polymeric material of claim 25, wherein said polymeric material is selected from the group consisting of polycaprolactone, poly(ethylene-co-vinyl acetate), poly(vinyl acetate), silicone gum rubber, poly-DL-lactic acid (DL-PLA), poly-L-lactic acid (L-PLA), polyorthoesters, polyiminocarbonates, aliphatic polycarbonates, polyphosphazenes, and mixtures thereof.
Claim 29
Dependent Claim
24 words
The polymeric material of claim 25, wherein said particles of said therapeutic drug can have a maximum cross-sectional dimension of up to 50 microns.
Claim 30
Dependent Claim
85 words
The polymeric material of claim 25, wherein said therapeutic drug is a drug selected from the group consisting of heparin, D-phe-pro-arg-chloromethylketone, dipyridamole, hirudin, recombinant hirudin, thrombin inhibitor, angiopeptin, angiotensin converting enzyme inhibitors, calcium channel blockers, colchicine, fibroblast growth factor antagonists, fish oil, omega 3- fatty acid, low molecular weight heparin, histamine antagonists, inhibitors of HMG-CoA reductase, methotrexate, monoclonal antibodies, nitroprusside, phosphodiesterase inhibitors, prostacyclin and prostacyclin analogues, prostaglandin inhibitor, PDGF antagonists, serotonin blockers, steroids, thioprotease inhibitors, triazolopyrimidine, alpha-interferon, and genetically engineered epithelial cells, and mixtures thereof.
Claim 31
Dependent Claim
31 words
The polymeric material of claim 25, wherein said particles of said therapeutic drug comprise up to 70% by weight of the total weight of the therapeutic drug and the polymeric material.
Claim 32
Dependent Claim
31 words
The polymeric material of claim 25, wherein said particles of said therapeutic drug comprise up to 40% by weight of the total weight of the therapeutic drug and the polymeric material.
Claim 33
Dependent Claim
26 words
The polymeric material of claim 25, wherein said polymeric material comprises a surface defining pores with a maximum cross-sectional dimension of less than about 10 microns.
Claim 34
Dependent Claim
11 words
The polymeric material of claim 25, further including a rate-controlling membrane.
Claim 35
Dependent Claim
43 words
The polymeric material of claim 32, wherein said rate-controlling membrane is formed to include a uniform distribution of a porosigen, said porosigen being selected from the group consisting of sodium chloride, lactose, sodium heparin, polyethylene glycol, polyethylene oxide/polypropylene oxide copolymers, and mixtures thereof.
Claim 36
Dependent Claim
24 words
The polymeric material of claim 32, wherein said rate-controlling membrane comprises a surface defining pores with a maximum cross-sectional dimension of about ten microns.
Claim 37
Dependent Claim
24 words
The polymeric material of claim 32, wherein said rate-controlling membrane comprises a surface defining pores with a maximum cross-sectional dimension of about one micron.
Claim 38
Dependent Claim
25 words
The polymeric material of claim 25, wherein said polymeric material containing said therapeutic drug is formed as a sheet at least about 25 microns thick.
Claim 39
Dependent Claim
24 words
The polymeric material of claim 36, wherein said sheet of polymeric material containing said therapeutic drug is further laminated to an intravascular stent structure.
Claim 40
Independent Claim
196 words
A method of incorporating a therapeutically effective amount of a therapeutic drug into a polymeric material for application to an intravascular stent, the method comprising the steps of: forming solid particles of a therapeutic drug to have a maximum cross-sectional dimension of about 10 microns; uniformly dispersing said solid particles of said therapeutic drug in said polymeric material such that said particles of said therapeutic drug form up to about 70% by weight of the total weight of the therapeutic drug and the polymeric material; uniformly dispersing a porosigen in said polymeric material together with said therapeutic drug, said porosigen being selected from the group consisting of sodium chloride, lactose, sodium heparin, polyethylene glycol, copolymers of polyethylene oxide and polypropylene oxide, and mixtures thereof; and applying a rate-controlling membrane over said polymeric material to control the release rate of said therapeutic drug from said polymeric material, said rate controlling membrane being formed of a polymeric material selected from the group consisting of polycaprolactone, poly(ethylene-co-vinyl acetate), poly(vinylacetate), silicone gum rubber, poly-DL-lactic acid (DL-PLA), poly-L-lactic acid (L-PLA), polyorthoesters, polyiminocarbonates, aliphatic polycarbonat polyphosphazenes, and mixtures thereof, said rate controlling membrane polymeric material containing a uniform dispersion of said porosigen.
Claim 41
Independent Claim
196 words
A method of incorporating a therapeutically effective amount of a therapeutic drug into a polymeric material for application to an intravascular stent, the method comprising the steps of: forming solid particles of a therapeutic drug to have a maximum cross-sectional dimension of about 10 microns; uniformly dispersing said solid particles of said therapeutic drug in said polymeric material such that said particles of said therapeutic drug form up to about 70% by weight of the total weight of the therapeutic drug and the polymeric material; uniformly dispersing a porosigen in said polymeric material together with said therapeutic drug, said porosigen being selected from the group consisting of sodium chloride, lactose, sodium heparin, polyethylene glycol, copolymers of polyethylene oxide and polypropylene oxide, and mixtures thereof; and applying a rate-controlling membrane over said polymeric material to control the release rate of said therapeutic drug from said polymeric material, said rate controlling membrane being formed of a polymeric material selected from the group consisting of polycaprolactone, poly(ethylene-co-vinyl acetate), poly(vinylacetate), silicone gum rubber, poly-DL-lactic acid (DL-PLA), poly-L-lactic acid (L-PLA), polyorthoesters, polyiminocarbonates, aliphatic polycarbonat polyphosphazenes, and mixtures thereof, said rate controlling membrane polymeric material containing a uniform dispersion of said porosigen.
Claim 42
Independent Claim
163 words
An apparatus containing a therapeutic drug for application to an intravascular stent for carrying and delivering said therapeutic drug within a blood vessel in which said intravascular stent is placed, comprising: a polymeric material having a thermal processing temperature no greater than about 100° C; particles of a therapeutic drug incorporated in said polymeric material; a porosigen uniformly dispersed in said polymeric material, said porosigen being selected from the group consisting of sodium chloride, lactose, sodium heparin, polyethylene glycol, copolymers of polyethylene oxide and polypropylene oxide, and mixtures thereof; and a rate-controlling membrane disposed over said polymeric material to control a rate of release of said therapeutic drug from said polymeric material, said rate controlling membrane being formed of a polymeric material selected from the group consisting of polycaprolactone, poly(ethylene-co-vinyl acetate), poly(vinyl acetate), silicone gum rubber, poly-DL-lactic acid (DL-PLA), poly-L-lactic acid (L-PLA), polyorthoesters, polyiminocarbonates, aliphatic polycarbonates, polyphosphazenes, and mixtures thereof, said rate controlling membrane polymeric material containing a uniform dispersion of said porosigen.
Claim 43
Independent Claim
163 words
An apparatus containing a therapeutic drug for application to an intravascular stent for carrying and delivering said therapeutic drug within a blood vessel in which said intravascular stent is placed, comprising: a polymeric material having a thermal processing temperature no greater than about 100° C; particles of a therapeutic drug incorporated in said polymeric material; a porosigen uniformly dispersed in said polymeric material, said porosigen being selected from the group consisting of sodium chloride, lactose, sodium heparin, polyethylene glycol, copolymers of polyethylene oxide and polypropylene oxide, and mixtures thereof; and a rate-controlling membrane disposed over said polymeric material to control a rate of release of said therapeutic drug from said polymeric material, said rate controlling membrane being formed of a polymeric material selected from the group consisting of polycaprolactone, poly(ethylene-co-vinyl acetate), poly(vinyl acetate), silicone gum rubber, poly-DL-lactic acid (DL-PLA), poly-L-lactic acid (L-PLA), polyorthoesters, polyiminocarbonates, aliphatic polycarbonates, polyphosphazenes, and mixtures thereof, said rate controlling membrane polymeric material containing a uniform dispersion of said porosigen.
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USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 2000-02-25 | 2000-08-26 | 2001-02-25 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 2004-02-25 | 2004-08-26 | 2005-02-25 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2008-02-25 | 2008-08-26 | 2009-02-25 | $7700.00 | Window Closed / Lapsed |