Post by aligator on May 8, 2007 13:21:33 GMT -5
Polymeric, fiber matrix delivery systems for bioactive compounds
Multifunctional systems for delivery of bioactive compounds incorporated within or between polymeric fibers in a matrix are provided. Also provided are methods of delivering bioactive compounds via implementation, coating and/or wrapping of these systems and methods for modulating the rate of release of bioactive compounds from these delivery systems.
Patent Agent: Licatla & Tyrrell P.C. - Marlton, NJ, US
Patent Inventors: Margaret A. Wheatley, Frank K. Ko, Dalia El-Sherif, Nikhil Dhoot, Saravanan Kanakasabai, Meriem Benjelloun, Baohua Han
Applicaton #: 20050158362 Class: 424426000 (USPTO)
Related Patents: Drug, Bio-affecting And Body Treating Compositions, Preparations Characterized By Special Physical Form, Implant Or Insert, Surgical Implant Or Material, Errodable, Resorbable, Or Dissolving
Brief Patent Description - Full Patent Description - Patent Application Claims
FIELD OF THE INVENTION
[0001] The present invention relates to delivery systems comprising polymeric fiber matrices, film coatings or braided/woven structures for the controlled release of bioactive compounds. The delivery systems of the present invention may be comprised of either biodegradable or nondegrading polymeric fibers. In one embodiment, these fibers have submicron and/or micron diameters. Bioactive compounds are included in the delivery system either by suspending the compound particles or dissolving the compound in the polymer solution used to produce the fibers.
BACKGROUND OF THE INVENTION
[0002] A number of polymer matrices for use in the controlled release and/or delivery of bioactive compounds, and for particular drugs, have been described.
[0003] U.S. Pat. No. 3,991,766 describes a medicament repository consisting of a surgical element in the form of tubes, sheets, sponges, gauzes or prosthetic devices of polyglycolic acid having incorporated therein an effective amount of a medicament.
[0004] U.S. Pat. No. 4,655,777 describes a method for producing a biodegradable prothesis or implant by encasing an effective amount of fibers of calcium phosphate or calcium aluminate in a matrix of polymer selected from the group consisting of polyglycolide, poly(DL-lactide), poly(L-lactide), polycaprolactone, polydioxanone, polyesteramides, copolyoxalates, polycarbonates, poly(glutamic-co-leucine) and blends, copolymers and terpolymers thereof to form a composite.
[0005] U.S. Pat. No. 4,818,542 discloses a method for preparing a spherical microporous polymeric network with interconnecting channels having a drug distributed within the channels.
[0006] U.S. Pat. No. 5,128,170 discloses a medical device and methods for manufacturing medical devices with a highly biocompatible surface wherein hydrophillic polymer is bonded onto the surface of the medical device covalently through a nitrogen atom.
[0007] U.S. Pat. No. 5,545,409 discloses a composition and method for controlled release of water-soluble proteins comprising a surface-eroding polymer matrix and water-soluble bioactive growth factors.
[0008] U.S. Pat. No. 5,769,830 discloses synthetic, biocompatible, biodegradable polymer fiber scaffolds for cell growth. Fibers are spaced apart by a distance of about 100 to 300 microns for diffusion and may comprise polyanhydrides, polyorthoesters, polyglycolic acid or polymethacrylate. The scaffolds may be coated withe materials such as agar, agarons, gelatin, gum arabic, basement membrane material, collagen type I, II, III, IV or V, fibronectin, laminin, glycosaminoglycans, and mixtures thereof.
[0009] U.S. Pat. No. 5,898,040 discloses a polymeric article for use in drug delivery systems which comprises a polymeric substrate with a highly uniform microporous polymeric surface layer on at least part of the substrate.
[0010] Encapsulation of a bioactive compound within a polymer matrix has also been described. For example, WO 93/07861 discloses polymer microspheres of 50 to 100 microns comprising a compound contained in a fixed oil within the polymer microsphere. U.S. Pat. No. 5,969,020 discloses a foam precursor comprising a crystalline thermoplastic polymer and solid crystalline additive for use in preparation of drug delivery systems.
[0011] Recently, it has been shown that polymer fibers of nanometer diameter can be electrospun from sulfuric acid into a coagulation bath (Reneker, D. H. and Chun, I. Nanotechnology 1996 7:216). In these studies more than 20 polymers including polyethylene oxide, nylon, polyimide, DNA, polyaramide and polyaniline were electrospun into electrically charged fibers which were then collected in sheets or other useful geometrical forms. Electrospinning techniques have also been applied to the production of high performance filters (Doshi, J. and Reneker, D. H. Journal of Electrostatics 1995 35:151; Gibson et al. AIChE Journal 1999 45:190) and for scaffolds in tissue engineering (Doshi, J. and Reneker, D. H. Journal of Electrostatics 1995 35:151; Ko et al. "The Dynamics of Cell-Fiber Architecture Interaction," Proceedings, Annual Meeting, Biomaterials Research Society, San Diego, Calif., April 1998; and WO 99/18893). WO 99/18893 describes a method for preparing nanofibrils from both nondegrading and biodegradable polymers for use as tissue engineering scaffolds.
[0012] The present invention relates to delivery systems for the controlled release of bioactive compounds which comprise polymeric fibers and the bioactive compound.
SUMMARY OF THE INVENTION
[0013] An object of the present invention is to provide a system for delivery of bioactive compounds comprising a bioactive compound incorporated within or between a polymeric fiber matrix or linear assembly, film coating or braided/woven structure.
[0014] Another object of the present invention is to provide a method for delivering a bioactive compound to a patient for controlled release of the bioactive compound in the patient. In one embodiment of this method of the present invention, the bioactive compound is incorporated into a polymeric fiber matrix or linear assembly or a braided or woven structure and implanted into the patient. In another embodiment, the bioactive compound is incorporated into a polymeric fiber film used to coat implants, tissue engineering scaffolds and other devices such as pumps and pacemakers which are then implanted into the patient. In yet another embodiment, the bioactive compound is incorporated into a polymeric fiber film used to wrap organs, tissues or vessels in a patient.
[0015] Another object of the present invention is to provide methods for modulating the rate of release of a bioactive compound from a delivery system for bioactive compounds comprising a bioactive compound incorporated within or between polymeric fibers. These methods include modulating loading of the bioactive compound incorporated with or between polymeric fiber, selecting polymers to produce the polymeric fibers which degrade at varying rates, varying polymeric concentration of the polymeric fibers and varying polymeric fiber diameter.
DETAILED DESCRIPTION OF THE INVENTION
[0016] Electrospinning is a simple and low cost electrostatic self-assembly method capable of fabricating a large variety of long, meter-length, organic polymer fibers with micron or submicron diameters, in linear, 2-D and 3-D architecture. Electrospinning techniques have been available since the 1930's (U.S. Pat. No. 1,975,504). In the electrospinning process, a high voltage electric field is generated between oppositely charged polymer fluid contained in a glass syringe with a capillary tip and a metallic collection screen. As the voltage is increased, the charged polymer solution is attracted to the screen. Once the voltage reaches a critical value, the charge overcomes the surface tension of the suspended polymer cone formed on the capillary tip of the syringe and a jet of ultrafine fibers is produced. As the charged fibers are splayed, the solvent quickly evaporates and the fibers are accumulated randomly on the surface of the collection screen. This results in a nonwoven mesh of nano and micron scale fibers. Varying the charge density (applied voltage), polymer solution concentration, solvent used, and the duration of electrospinning can control the fiber diameter and mesh thickness. Other electrospinning parameters which may be varied routinely to effect the fiber matrix properties include distance between the needle and collection plate, the angle of syringe with respect to the collection plate, and the applied voltage.
[0017] In the present invention, electrospinning is used to produce polymeric fiber matrices with the capability of releasing bioactive compounds in a controlled manner over a selected period of time. In one embodiment, the delivery system of the present invention is used to maintain delivery of a steady concentration of bioactive compound. In another embodiment, the delivery system is used in pulsed delivery of the bioactive compound wherein the compound is released in multiple phases in accordance with either rapid or slow degradation of the polymer fibers or diffusion of the bioactive compound from the polymer fibers. In yet another embodiment, the delivery system is used to obtain a delayed release of a bioactive compound. For example, the bioactive compound-containing fiber polymer matrix can be coated with a layer of nonwoven polymer fiber matrix with no bioactive compound. In this embodiment, different polymers with different degradation times can be used to obtain the desired time delays.
[0018] The delivery systems of the present invention can be used to deliver a single bioactive compound, more than one Ibioactive compound at the same time, or more than one bioactive compound in sequence. Thus, as used herein, the phrases "a bioactive compound" and "the bioactive compound", are meant to be inclusive of one or more bioactive compounds.
[0019] For purposes of the present invention by "fiber" it is meant to include fibrils ranging in diameter from submicron, i.e. approximately 1 to 100 nanometers (10.sup.-9 to 10.sup.-7 meters) to micron, i.e. approximately 1-1000 micrometers. The bioactive compound is incorporated within the polymeric fibers either by suspension of compound particles or dissolution of the compound in the solvent used to dissolve the polymer prior to electrospinning of the polymeric fibers. For purposes of the present invention, by "incorporated within" it is meant to include embodiments wherein the bioactive compound is inside the fiber as well as embodiments wherein the bioactive compound is dispersed between the fibers. The polymeric fibers comprising the bioactive compound can be arranged as matrices, linear assemblies, or braided or woven structures. In addition, the fibers which release a bioactive compound can serve as film coatings for devices such as implants, tissue engineering scaffolds, pumps, pacemakers and other composites.
[0020] These fiber assemblies can be spun from any polymer which can be dissolved in a solvent. The solvent can be either organic or aqueous depending upon the selected polymer. Examples of polymers which can be used in production of the polymeric fibers of the present invention include, but are not limited to, nondegradable polymers such as polyethylenes, polyurethanes, and EVA, and biodegradable polymers such as poly(lactic acid-glycolic acid), poly(lactic acid), poly(glycolic acid), poly(glaxanone), poly(orthoesters), poly(pyrolic acid) and poly(phosphazenes).
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Full patent description for Polymeric, fiber matrix delivery systems for bioactive compounds
Brief Patent Description - Full Patent Description - Patent Application Claims
Click on the above for other options relating to this Polymeric, fiber matrix delivery systems for bioactive compounds patent application.
Related Patent Applications:
20070098759 - Method for regenerating cartilage - Disclosed is a method for regenerating articular cartilage in an animal comprising administering a therapeutically effective amount of a non-demineralized particulate articular cartilage having a distribution of particle sizes within the range of from about 60 microns to about 500 microns. ...
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Previous Patent Application:
Multifaceted endovascular stent coating for preventing restenosis
Next Patent Application:
Drug delivery device with mechanical locking mechanism
Industry Class:
Drug, bio-affecting and body treating compositions
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Patent data source: United States Patent and Trademark Office
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Thank you for viewing the Polymeric, fiber matrix delivery systems for bioactive compounds patent info.
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Multifunctional systems for delivery of bioactive compounds incorporated within or between polymeric fibers in a matrix are provided. Also provided are methods of delivering bioactive compounds via implementation, coating and/or wrapping of these systems and methods for modulating the rate of release of bioactive compounds from these delivery systems.
Patent Agent: Licatla & Tyrrell P.C. - Marlton, NJ, US
Patent Inventors: Margaret A. Wheatley, Frank K. Ko, Dalia El-Sherif, Nikhil Dhoot, Saravanan Kanakasabai, Meriem Benjelloun, Baohua Han
Applicaton #: 20050158362 Class: 424426000 (USPTO)
Related Patents: Drug, Bio-affecting And Body Treating Compositions, Preparations Characterized By Special Physical Form, Implant Or Insert, Surgical Implant Or Material, Errodable, Resorbable, Or Dissolving
Brief Patent Description - Full Patent Description - Patent Application Claims
FIELD OF THE INVENTION
[0001] The present invention relates to delivery systems comprising polymeric fiber matrices, film coatings or braided/woven structures for the controlled release of bioactive compounds. The delivery systems of the present invention may be comprised of either biodegradable or nondegrading polymeric fibers. In one embodiment, these fibers have submicron and/or micron diameters. Bioactive compounds are included in the delivery system either by suspending the compound particles or dissolving the compound in the polymer solution used to produce the fibers.
BACKGROUND OF THE INVENTION
[0002] A number of polymer matrices for use in the controlled release and/or delivery of bioactive compounds, and for particular drugs, have been described.
[0003] U.S. Pat. No. 3,991,766 describes a medicament repository consisting of a surgical element in the form of tubes, sheets, sponges, gauzes or prosthetic devices of polyglycolic acid having incorporated therein an effective amount of a medicament.
[0004] U.S. Pat. No. 4,655,777 describes a method for producing a biodegradable prothesis or implant by encasing an effective amount of fibers of calcium phosphate or calcium aluminate in a matrix of polymer selected from the group consisting of polyglycolide, poly(DL-lactide), poly(L-lactide), polycaprolactone, polydioxanone, polyesteramides, copolyoxalates, polycarbonates, poly(glutamic-co-leucine) and blends, copolymers and terpolymers thereof to form a composite.
[0005] U.S. Pat. No. 4,818,542 discloses a method for preparing a spherical microporous polymeric network with interconnecting channels having a drug distributed within the channels.
[0006] U.S. Pat. No. 5,128,170 discloses a medical device and methods for manufacturing medical devices with a highly biocompatible surface wherein hydrophillic polymer is bonded onto the surface of the medical device covalently through a nitrogen atom.
[0007] U.S. Pat. No. 5,545,409 discloses a composition and method for controlled release of water-soluble proteins comprising a surface-eroding polymer matrix and water-soluble bioactive growth factors.
[0008] U.S. Pat. No. 5,769,830 discloses synthetic, biocompatible, biodegradable polymer fiber scaffolds for cell growth. Fibers are spaced apart by a distance of about 100 to 300 microns for diffusion and may comprise polyanhydrides, polyorthoesters, polyglycolic acid or polymethacrylate. The scaffolds may be coated withe materials such as agar, agarons, gelatin, gum arabic, basement membrane material, collagen type I, II, III, IV or V, fibronectin, laminin, glycosaminoglycans, and mixtures thereof.
[0009] U.S. Pat. No. 5,898,040 discloses a polymeric article for use in drug delivery systems which comprises a polymeric substrate with a highly uniform microporous polymeric surface layer on at least part of the substrate.
[0010] Encapsulation of a bioactive compound within a polymer matrix has also been described. For example, WO 93/07861 discloses polymer microspheres of 50 to 100 microns comprising a compound contained in a fixed oil within the polymer microsphere. U.S. Pat. No. 5,969,020 discloses a foam precursor comprising a crystalline thermoplastic polymer and solid crystalline additive for use in preparation of drug delivery systems.
[0011] Recently, it has been shown that polymer fibers of nanometer diameter can be electrospun from sulfuric acid into a coagulation bath (Reneker, D. H. and Chun, I. Nanotechnology 1996 7:216). In these studies more than 20 polymers including polyethylene oxide, nylon, polyimide, DNA, polyaramide and polyaniline were electrospun into electrically charged fibers which were then collected in sheets or other useful geometrical forms. Electrospinning techniques have also been applied to the production of high performance filters (Doshi, J. and Reneker, D. H. Journal of Electrostatics 1995 35:151; Gibson et al. AIChE Journal 1999 45:190) and for scaffolds in tissue engineering (Doshi, J. and Reneker, D. H. Journal of Electrostatics 1995 35:151; Ko et al. "The Dynamics of Cell-Fiber Architecture Interaction," Proceedings, Annual Meeting, Biomaterials Research Society, San Diego, Calif., April 1998; and WO 99/18893). WO 99/18893 describes a method for preparing nanofibrils from both nondegrading and biodegradable polymers for use as tissue engineering scaffolds.
[0012] The present invention relates to delivery systems for the controlled release of bioactive compounds which comprise polymeric fibers and the bioactive compound.
SUMMARY OF THE INVENTION
[0013] An object of the present invention is to provide a system for delivery of bioactive compounds comprising a bioactive compound incorporated within or between a polymeric fiber matrix or linear assembly, film coating or braided/woven structure.
[0014] Another object of the present invention is to provide a method for delivering a bioactive compound to a patient for controlled release of the bioactive compound in the patient. In one embodiment of this method of the present invention, the bioactive compound is incorporated into a polymeric fiber matrix or linear assembly or a braided or woven structure and implanted into the patient. In another embodiment, the bioactive compound is incorporated into a polymeric fiber film used to coat implants, tissue engineering scaffolds and other devices such as pumps and pacemakers which are then implanted into the patient. In yet another embodiment, the bioactive compound is incorporated into a polymeric fiber film used to wrap organs, tissues or vessels in a patient.
[0015] Another object of the present invention is to provide methods for modulating the rate of release of a bioactive compound from a delivery system for bioactive compounds comprising a bioactive compound incorporated within or between polymeric fibers. These methods include modulating loading of the bioactive compound incorporated with or between polymeric fiber, selecting polymers to produce the polymeric fibers which degrade at varying rates, varying polymeric concentration of the polymeric fibers and varying polymeric fiber diameter.
DETAILED DESCRIPTION OF THE INVENTION
[0016] Electrospinning is a simple and low cost electrostatic self-assembly method capable of fabricating a large variety of long, meter-length, organic polymer fibers with micron or submicron diameters, in linear, 2-D and 3-D architecture. Electrospinning techniques have been available since the 1930's (U.S. Pat. No. 1,975,504). In the electrospinning process, a high voltage electric field is generated between oppositely charged polymer fluid contained in a glass syringe with a capillary tip and a metallic collection screen. As the voltage is increased, the charged polymer solution is attracted to the screen. Once the voltage reaches a critical value, the charge overcomes the surface tension of the suspended polymer cone formed on the capillary tip of the syringe and a jet of ultrafine fibers is produced. As the charged fibers are splayed, the solvent quickly evaporates and the fibers are accumulated randomly on the surface of the collection screen. This results in a nonwoven mesh of nano and micron scale fibers. Varying the charge density (applied voltage), polymer solution concentration, solvent used, and the duration of electrospinning can control the fiber diameter and mesh thickness. Other electrospinning parameters which may be varied routinely to effect the fiber matrix properties include distance between the needle and collection plate, the angle of syringe with respect to the collection plate, and the applied voltage.
[0017] In the present invention, electrospinning is used to produce polymeric fiber matrices with the capability of releasing bioactive compounds in a controlled manner over a selected period of time. In one embodiment, the delivery system of the present invention is used to maintain delivery of a steady concentration of bioactive compound. In another embodiment, the delivery system is used in pulsed delivery of the bioactive compound wherein the compound is released in multiple phases in accordance with either rapid or slow degradation of the polymer fibers or diffusion of the bioactive compound from the polymer fibers. In yet another embodiment, the delivery system is used to obtain a delayed release of a bioactive compound. For example, the bioactive compound-containing fiber polymer matrix can be coated with a layer of nonwoven polymer fiber matrix with no bioactive compound. In this embodiment, different polymers with different degradation times can be used to obtain the desired time delays.
[0018] The delivery systems of the present invention can be used to deliver a single bioactive compound, more than one Ibioactive compound at the same time, or more than one bioactive compound in sequence. Thus, as used herein, the phrases "a bioactive compound" and "the bioactive compound", are meant to be inclusive of one or more bioactive compounds.
[0019] For purposes of the present invention by "fiber" it is meant to include fibrils ranging in diameter from submicron, i.e. approximately 1 to 100 nanometers (10.sup.-9 to 10.sup.-7 meters) to micron, i.e. approximately 1-1000 micrometers. The bioactive compound is incorporated within the polymeric fibers either by suspension of compound particles or dissolution of the compound in the solvent used to dissolve the polymer prior to electrospinning of the polymeric fibers. For purposes of the present invention, by "incorporated within" it is meant to include embodiments wherein the bioactive compound is inside the fiber as well as embodiments wherein the bioactive compound is dispersed between the fibers. The polymeric fibers comprising the bioactive compound can be arranged as matrices, linear assemblies, or braided or woven structures. In addition, the fibers which release a bioactive compound can serve as film coatings for devices such as implants, tissue engineering scaffolds, pumps, pacemakers and other composites.
[0020] These fiber assemblies can be spun from any polymer which can be dissolved in a solvent. The solvent can be either organic or aqueous depending upon the selected polymer. Examples of polymers which can be used in production of the polymeric fibers of the present invention include, but are not limited to, nondegradable polymers such as polyethylenes, polyurethanes, and EVA, and biodegradable polymers such as poly(lactic acid-glycolic acid), poly(lactic acid), poly(glycolic acid), poly(glaxanone), poly(orthoesters), poly(pyrolic acid) and poly(phosphazenes).
Continue reading...
Full patent description for Polymeric, fiber matrix delivery systems for bioactive compounds
Brief Patent Description - Full Patent Description - Patent Application Claims
Click on the above for other options relating to this Polymeric, fiber matrix delivery systems for bioactive compounds patent application.
Related Patent Applications:
20070098759 - Method for regenerating cartilage - Disclosed is a method for regenerating articular cartilage in an animal comprising administering a therapeutically effective amount of a non-demineralized particulate articular cartilage having a distribution of particle sizes within the range of from about 60 microns to about 500 microns. ...
###
How KEYWORD MONITOR works... a FREE service from FreshPatents
1. Sign up (takes 30 seconds). 2. Fill in the keywords to be monitored.
3. Each week you receive an email with patent applications related to your keywords.
Start now! - Receive info on patent apps like Polymeric, fiber matrix delivery systems for bioactive compounds or other areas of interest.
###
Previous Patent Application:
Multifaceted endovascular stent coating for preventing restenosis
Next Patent Application:
Drug delivery device with mechanical locking mechanism
Industry Class:
Drug, bio-affecting and body treating compositions
###
Design/code © 2004-2006 Freshpatents.com. Website Terms and Conditions
Patent data source: United States Patent and Trademark Office
Information published here is an abstract for research/educational purposes.
Complete official applications are on file at the USPTO and may contain additional data/images.
FreshPatents.com is not affiliated with or endorsed by the USPTO or firms/individuals related to listed patents.
FreshPatents.com Support
Thank you for viewing the Polymeric, fiber matrix delivery systems for bioactive compounds patent info.
IP-related news and info