Rapamycin 40-O-Cyclic Hydrocarbon Esters, Compositions and Methods

A new class of rapamycin 40-O-cyclic hydrocarbon esters is disclosed. The 40-O position of the rapamycin ester has the form 40-O—R, where R is C(O)—(CH 2 ) n -X, n is 0, 1 or 2, and X is a cyclic hydrocarbon having 3-8 carbons, optionally containing one or more unsaturated bonds, and one or more linear (CH 2 )) and/or cyclic (X) carbon atoms may have an OH or halide group. Also disclosed are therapeutic compositions and methods that employ the novel analogs.

DRUG DELIVERY ENDOVASCULAR STENT AND METHOD OF USE

An improvement in drug-eluting stents, and method of their making, are disclosed. The surface of a metal stent is roughened to have a surface roughness of at least about 20 μin (0.5 μm) and a surface roughness range of between about 300-700 μin (7.5-17.5 μm). The roughened stent surface is covered with a polymer-free coating of a limus drug, to a coating thickness greater than the range of surface roughness of the roughened stent surface. 1. A method for making an expandable , metal stent having metal filaments coated with a polymer-free limus drug where the rate of occurrence and/or extent of restenosis or thrombosis resulting from vascular injury in a subject , is reduced relative to that observed by placing at a site of injury , a bare-metal expandable stent formed of interconnected metal filaments or by having a coating on the outer surface of the stent filaments of a polymer carrier containing a limus drug , the method comprising:roughening regions of the outer surface of the stent filaments to a surface roughness (Ra) of between 20-40 μin (0.5-1 μm), and a surface roughness range (Rt) of between 300-700 μin (7.5-17.5 μm), andcoating the roughened regions of the stent filaments with a polymer-free limus drug, to a coating thickness greater than the range of surface roughness of the roughened stent surface.2. The method according to claim 1 , wherein said roughening is carried out by abrading the outer surface regions of the stent filaments with a pressurized stream of abrasive particles.3. The method according to claim 1 , wherein said roughening is carried out by forming a hydrocarbon-film mask over regions of the surface of the stent filaments claim 1 , selectively removing stent material not covered by the mask claim 1 , and removing the mask.4. The method according to claim 1 , wherein said roughening is carried out by laser etching the outer surface regions of the stent filaments.5. The method according to claim 1 , wherein said roughening is carried out ...

Rapamycin 40-O-cyclic hydrocarbon esters, compositions and methods

A new class of rapamycin 40-O-cyclic hydrocarbon esters is disclosed. The 40-O position of the rapamycin ester has the form 40-O—R, where R is C(O)—(CH 2 )n-X, n is 0, 1 or 2, and X is a cyclic hydrocarbon having 3-8 carbons, optionally containing one or more unsaturated bonds, and one or more linear (CH 2 )n) and/or cyclic (X) carbon atoms may have an OH or halide group. Also disclosed are therapeutic compositions and methods that employ the novel analogs.

Drug-delivery endovascular stent and method of use

The invention relates to a drug-delivery endovascular stent and a method of use. More specifically, the invention relates to a radially expandable, endovascular stent designed for placement at a site of vascular injury, for inhibiting restenosis at the site, a method of using, and a method of making the stent. The stent includes a radially expandable body formed of one or more metallic filaments where at least one surface of the filaments has a roughened or abraded surface. The stent may include a therapeutic agent on the abraded surface.

Drug delivery endovascular stent and method of use

An improvement in drug-eluting stents, and method of their making, are disclosed. The surface of a metal stent is roughened to have a surface roughness of at least about 20 μin (0.5 μm) and a surface roughness range of between about 300-700 μin (7.5-17.5 μm). The roughened stent surface is covered with a polymer-free coating of a limus drug, to a coating thickness greater than the range of surface roughness of the roughened stent surface.

Rapamycin 40-O-cyclic hydrocarbon esters, compositions and methods

A new class of rapamycin 40-O-cyclic hydrocarbon esters is disclosed. The 40-O position of the rapamycin ester has the form 40-O—R, where R is C(O)—(CH 2 ) n -X, n is 0, 1 or 2, and X is a cyclic hydrocarbon having 3-8 carbons, optionally containing one or more unsaturated bonds, and one or more linear (CH 2 )) and/or cyclic (X) carbon atoms may have an OH or halide group. Also disclosed are therapeutic compositions and methods that employ the novel analogs.

DRUG DELIVERY ENDOVASCULAR STENT AND METHOD OF USE

A radially expandable, endovascular stent designed for placement at a site of vascular injury, for inhibiting restenosis at the site, a method of using, and a method of making the stent. The stent includes a radially expandable body formed of one or more metallic filaments where at least one surface of the filaments has a roughened or abraded surface. The stent may include a therapeutic agent on the abraded surface. 17-. (canceled)8. A method for making a stent for reducing the rate of occurrence and/or extent of restenosis or thrombosis resulting from vascular injury in a subject , relative to that observed by placing at the site of injury , a bare-metal expandable stent formed of interconnected metal filaments and by having a coating on the outer surface of the stent filaments of a polymer carrier containing a limus drug , the method comprising:roughening the outer surface regions of the stent filaments to a surface roughness (Ra) of at least about 20 μin (0.5 μm), and a surface roughness range (Rt) of between about 300-700 μin (7.5-17.5 μm), andcoating the roughened regions of the stent filaments with a polymer-free coating of the limus drug, to a coating thickness greater than the range of surface roughness of the roughened stent surface.9. A method for making an expandable stent formed of interconnected metal filaments for administering an anti-restenosis drug , the method comprising;roughening the outer surface regions of the stent filaments to a surface roughness of at least about 20 μin (0.5 μm), and a surface roughness range of between about 300-700 μin (7.5-17.5 μm); and, coating the outer surface of the stent with a polymer-free limus drug coating.10. The method according to or , wherein the stent filaments are roughened to a surface roughness of between about 20-40 μin (0.5 to 1 μm).11. The method according to or , wherein said roughening is carried out by abrading the outer surface regions of the stent filaments with a pressurized stream of abrasive ...

DRUG DELIVERY ENDOVASCULAR STENT AND METHOD OF USE

An improvement in drug-eluting stents, and method of their making, are disclosed. The surface of a metal stent is roughened to have a surface roughness of at least about 20 μin (0.5 μm) and a surface roughness range of between about 300-700 μin (7.5-17.5 μm). The roughened stent surface is covered with a polymer-free coating of a limus drug, to a coating thickness greater than the range of surface roughness of the roughened stent surface. 1. A method for making a stent for reducing the rate of occurrence and/or extent of restenosis or thrombosis resulting from vascular injury in a subject , relative to that observed by placing at the site of injury , a bare-metal expandable stent formed of interconnected metal filaments and by having a coating on the outer surface of the stent filaments of a polymer carrier containing a limus drug , the method comprising:roughening the outer surface regions of the stent filaments to a surface roughness (Ra) of at least about 20 μin (0.5 μm), and a surface roughness range (Rt) of between about 300-700 μin (7.5-17.5 μm), and coating the roughened regions of the stent filaments with a polymer-free coating of the limus drug, to a coating thickness greater than the range of surface roughness of the roughened stent surface.2. A method for making an expandable stent formed of interconnected metal filaments for administering an anti-restenosis drug , the method comprising;roughening the outer surface regions of the stent filaments to a surface roughness of at least about 20 μin (0.5 μm), and a surface roughness range of between about 300-700 μin (7.5-17.5 μm); and, coating the outer surface of the stent with a polymer-free limus drug coating.3. The method according to claim 1 , wherein the stent filaments are roughened to a surface roughness of between about 20-40 μin (0.5 to 1 μm).4. The method according to claim 1 , wherein said roughening is carried out by abrading the outer surface regions of the stent filaments with a pressurized ...

DRUG-DELIVERY ENDOVASCULAR STENT AND METHOD OF FORMING THE SAME

An intravascular stent and method for inhibiting restenosis, following vascular injury, is disclosed. The stent has an expandable, linked-filament body and a drug-release coating formed on the stent-body filaments, for contacting the vessel injury site when the stent is placed in-situ in an expanded condition. The coating releases, for a period of at least 4 weeks, a restenosis-inhibiting amount of a monocyclic triene immunosuppressive compound having an alkyl group substituent at carbon position 40 in the compound. The stent, when used to treat a vascular injury, gives good protection against clinical restenosis, even when the extent of vascular injury involves vessel overstretching by more than 30% diameter. Also disclosed is a stent having a drug-release coating composed of (i) 10 and 60 weight percent poly-dl-Iactide polymer substrate and (ii) 40-90 weight percent of an anti-restenosis compound, and a polymer undercoat having a thickness of between 1-5 microns. 2. The stent of claim 1 , wherein the filaments are poly-l-lactide claim 1 , and the polymer substrate in the coating is selected from the group consisting of poly-l-lactide or poly-dl-lactide.3. The stent of wherein the drug-release coating of poly-lactide polymer is a co-polymer.4. The stent of wherein the co-polymer is comprises poly-lactide and ε-caprolactone.5. The stent of claim 1 , wherein the polymer substrate in the coating is formed of poly-dl-lactide having a thickness between 3-20 microns.6. The stent of claim 3 , which further includes a parylene polymer undercoat having a thickness of between 1-3 microns claim 3 , disposed between the filaments of the stent body and said poly-lactide coating.7. The stent of claim 3 , wherein said coating includes the compound at an initial concentration of between 50 and 75 weight percent of coating.8. The stent of claim 1 , further comprising a polymer undercoat disposed between the filaments of the stent body and said drug-release coating.9. The stent of ...

Intratumoral Drug Delivery Materials and Methods for Treating Breast Cancer

Generally, the invention is in relation to the field of drug delivery devices to augment standard radiation therapy and methods of making and using same. Specifically, this technology utilizes a controlled release of drug from a coated balloon for local intratumoral drug delivery to breast tissue to supplement or replace standard radiation therapy. 115.-. (canceled)16. A drug eluting device , comprising a primer layer containing a water soluble material layer and a multi-part drug layer having a first part and optionally a second part , wherein the first part comprises a macrocyclic triene immunosuppressive compound and the second part comprises at least one polymer-free excipient , wherein polymer-free excipient is a fatty alcohol or fatty aldehyde or a fatty acid or a nonionic surfactant.17. The medical device of claim 16 , wherein the device is a drug eluting balloon catheter.18. The device of claim 16 , wherein the water soluble material is a globular serum protein having an approximate molecular weight of between 65-70 kD.19. The device of claim 16 , wherein the water soluble material comprises a serum protein having at least 90% identity to SEQ ID NO: 1.20. The device of claim 16 , wherein the water soluble material is human serum albumin.21. The device of claim 16 , wherein the multi-part drug layer is formulated as a single formulation and applied after the primer layer has been applied to a surface of the balloon catheter.24. The device of claim 16 , wherein the macrocyclic triene compound is rapamycin claim 16 , everolimus claim 16 , zotarolimus claim 16 , Biolimus or temsirolimus.25. The device of claim 16 , wherein the multi-part drug layer contains one of tacrolimus claim 16 , paclitaxel claim 16 , docetaxel claim 16 , analogs thereof or mixtures thereof.26. The device of claim 16 , wherein polymer-free excipient is a linear fatty alcohol or fatty aldehyde or a fatty acid or a nonionic surfactant containing at least 12 carbon atoms.27. The device of ...

Covered Stent For Local Drug Delivery

The present invention relates generally to an endoprosthesis for maintaining patency of a body vessel, e.g., a stent, in a basically tubular configuration comprised of a structural lattice with a mesh covering which is capable of storing releasing one or more drugs to and penetrating into surrounding tissue. 1. A drug eluting stent system for use in delivering at least one therapeutic agent to a target , preferably the bile or pancreatic duct , comprising:(a) a stent capable of radial expansion; and(b) a coating, wherein the coating is composed of a porous surface covering and at least one therapeutic agent, wherein the at least one therapeutic agent is an antiproliferative agent and wherein the stent is encapsulated by the coating.2. The drug eluting stent system of claim 1 , wherein the at least one therapeutic agent is a macrocyclic triene immunosuppressive compound.5. The drug eluting stent system of claim 1 , wherein the porous surface covering is a nonwoven fabric.6. The drug eluting stent system of claim 5 , wherein the nonwoven fabric is composed of electrospun fibers.7. The drug eluting stent system of claim 6 , wherein the electrospun fibers are composed of a polymer selected from the group comprising or consisting of include polytetrafluoroethylene claim 6 , fluorinated ethylene propylene claim 6 , Dacron claim 6 , polyethylene terephthalate claim 6 , polyurethanes claim 6 , polycarbonate claim 6 , polypropylene claim 6 , Pebax claim 6 , polyethylene and biological polymers such as collagen claim 6 , fibrin claim 6 , and elastin.8. The drug eluting stent system of claim 1 , wherein the porous surface covering has a porosity of within the range of 20% to 40% of the surface area.9. The drug eluting stent system of claim 1 , wherein the porous surface covering has a porosity of within the range of 20% to 40% of the surface area at the abluminal surface and of less than 5% of the surface area at the luminal surface.10. The drug eluting stent system of claim 1 ...

Rapamycin 40-O-Cyclic Hydrocarbon Esters, Compositions and Methods

A new class of rapamycin 40-O-cyclic hydrocarbon esters is disclosed. The 40-O position of the rapamycin ester has the form 40-O—R, where R is C(O)—(CH 2 ) n —X, n is 0, 1 or 2, and X is a cyclic hydrocarbon having 3-8 carbons, optionally containing one or more unsaturated bonds, and one or more linear (CH 2 ) n ) and/or cyclic (X) carbon atoms may have an OH or halide group. Also disclosed are therapeutic compositions and methods that employ the novel analogs.

DRUG-DELIVERY ENDOVASCULAR STENT AND METHOD OF FORMING THE SAME

An intravascular stent and method for inhibiting restenosis, following vascular injury, is disclosed. The stent has an expandable, linked-filament body and a drug-release coating formed on the stent-body filaments, for contacting the vessel injury site when the stent is placed in-situ in an expanded condition. The coating releases, for a period of at least 4 weeks, a restenosis-inhibiting amount of a monocyclic triene immunosuppressive compound having an alkyl group substituent at carbon position 40 in the compound. The stent, when used to treat a vascular injury, gives good protection against clinical restenosis, even when the extent of vascular injury involves vessel overstretching by more than 30% diameter. Also disclosed is a stent having a drug-release coating composed of (i) 10 and 60 weight percent poly-dl-lactide polymer substrate and (ii) 40-90 weight percent of an anti-restenosis compound, and a polymer undercoat having a thickness of between 1-5 microns. 2. The stent of claim 1 , wherein the filaments are poly-l-lactide claim 1 , and the polymer substrate in the coating is selected from the group consisting of poly-l-lactide or poly-dl-lactide.3. The stent of wherein the drug-release coating of poly-lactide polymer is a co-polymer.4. The stent of wherein the co-polymer is comprises poly-lactide and ε-caprolactone.5. The stent of claim 1 , wherein the polymer substrate in the coating is formed of poly-dl-lactide having a thickness between 3-20 microns.6. The stent of claim 3 , which further includes a parylene polymer undercoat having a thickness of between 1-3 microns claim 3 , disposed between the filaments of the stent body and said poly-lactide coating.7. The stent of claim 3 , wherein said coating includes the compound at an initial concentration of between 50 and 75 weight percent of coating.8. The stent of claim 1 , further comprising a polymer undercoat disposed between the filaments of the stent body and said drug-release coating.9. The stent of ...

INTRACRANIAL DRUG DELIVERY MATERIALS AND METHODS

This application relates generally to the field of minimally invasive delivery of therapeutic agents. Specifically, the present invention provides for materials and methods directed to minimally invasive, targeted delivery of agents such as drugs, penetrants, blood barrier augmentation agents or other compounds to certain localized brain regions through the use of delivery balloon catheters. 110.-. (canceled)11. A medical device for intracranial delivery of therapeutic agents , the medical device comprising a balloon catheter , wherein the balloon comprises a first coating and a second coating , and further wherein the second coating is applied on top of the first coating.12. The medical device of claim 11 , wherein the first coating comprises at least one water soluble polymer.13. The medical device of claim 12 , wherein the at least one water soluble polymer comprises a globular serum protein having an approximate molecular weight of between 65-70 kD.14. The medical device of 11 claim claim 12 , wherein the second coating is comprised of a formulation having a first component and optionally a second component.17. The medical device of claim 14 , wherein the first component of the formulation consists of one of carmustine claim 14 , temozolomide claim 14 , lomustine claim 14 , procarbazine or vincristine.18. The medical device of claim 14 , wherein the second component is a non-polymer claim 14 , non-ionic claim 14 , linear hydrocarbon or surfactant selected from the group consisting of a lipoic fatty alcohol or a fatty aldehyde or a fatty acid or combinations thereof.19. The medical device of claim 18 , wherein a hydrocarbon or surfactant is a fatty alcohol having the formula CHO claim 18 , wherein x is at least 18 and at the most 35 claim 18 , and y is at least 38 and at the most 72.20. A method of treating an individual having a primary brain tumor claim 18 , the method comprising:(a) providing a balloon catheter comprising a first coating and a second coating ...

RAPAMYCIN 40-O-CYCLIC HYDROCARBON ESTERS, COMPOSITIONS AND METHODS

A new class of rapamycin 40-O-cyclic hydrocarbon esters is disclosed. The 40-O position of the rapamycin ester has the form 40-O—R, where R is C(O)—(CH)n-X, n is 0, 1 or 2, and X is a cyclic hydrocarbon having 3-8 carbons, optionally containing one or more unsaturated bonds, and one or more linear (CH)n) and/or cyclic (X) carbon atoms may have an OH or halide group. Also disclosed are therapeutic compositions and methods that employ the novel analogs. 3. A method of treating (i) restenosis; (ii) wound healing; (iii) vascular injury; (iv) vascular inflammation; (v) transplantation rejection; (vi) proliferative ophthalmic diseases claim 1 , including wet age-related macular degeneration (AMD) and diabetic macular edema (DME); (vii) uveitis claim 1 , or (viii) cancer in a mammal claim 1 , by administering to the mammal claim 1 , a therapeutic amount of the rapamycin 40-O-cyclic hydrocarbon ester of .4. The method of claim 3 , for inhibiting restenosis at a vascular injury site claim 3 , wherein the rapamycin 40-O-cyclic hydrocarbon ester is administered from a drug-eluting stent placed at the vascular injury site.5. The method of claim 4 , wherein the drug-eluting stent has an expandable stent body formed of one or more filaments claim 4 , and carried thereon claim 4 , a coating containing between 20 and 100 weight percent of the rapamycin 40-O-cyclic hydrocarbon ester and between 0 and 80 weight percent of a polymer.6. The method of claim 5 , wherein the stent coating contains between 20 and 60 weight percent of the rapamycin 40-O-cyclic hydrocarbon ester and 40 and 80 weight percent of at least one polymer selected from the group consisting of polyanhydride claim 5 , poly(glycolic acid) claim 5 , poly(glycolide) claim 5 , poly(L-lactide) claim 5 , poly(d claim 5 ,l-lactide) claim 5 , poly(L-lactic acid) claim 5 , poly(d claim 5 ,l-lactic acid) claim 5 , poly(caprolactone) claim 5 , poly(trimethylene carbonate) claim 5 , polyester amide claim 5 , polyhydroxyalkanoate ...

Rapamycin 40-O-Cyclic Hydrocarbon Esters, Compositions and Methods

A new class of rapamycin 40-O-cyclic hydrocarbon esters is disclosed. The 40-O position of the rapamycin ester has the form 40-O—R, where R is C(O)—(CH 2 ) n —X, n is 0, 1 or 2, and X is a cyclic hydrocarbon having 3-8 carbons, optionally containing one or more unsaturated bonds, and one or more linear (CH 2 ) n ) and/or cyclic (X) carbon atoms may have an OH or halide group. Also disclosed are therapeutic compositions and methods that employ the novel analogs.

Rapamycin 40-O-Cyclic Hydrocarbon Esters, Compositions and Methods

A new class of rapamycin 40-O-cyclic hydrocarbon esters is disclosed. The 40-O position of the rapamycin ester has the form 40-O—R, where R is C(O)—(CH2)n—X, n is 0, 1 or 2, and X is a cyclic hydrocarbon having 3-8 carbons, optionally containing one or more unsaturated bonds, and one or more linear (CH2)n) and/or cyclic (X) carbon atoms may have an OH or halide group. Also disclosed are therapeutic compositions and methods that employ the novel analogs.

Drug releasing coatings for medical devices and methods of making same

Generally, the invention is in relation to the field of drug releasing insertable devices and methods of making and using same. Specifically, this technology relates to controlled release of drug from a coated balloon directly into affected tissue regions within the body of an individual. 115.-. (canceled)16. A drug eluting device , comprising a primer layer containing a water soluble material layer and a multi-part drug layer having a first part and a second part , wherein the first part comprises a macrocyclic triene immunosuppressive compound and the second part comprises at least one polymer-free excipient , wherein polymer-free excipient is a fatty alcohol or fatty aldehyde or a fatty acid or a nonionic surfactant.17. The medical device of claim 16 , wherein the device is a drug eluting balloon catheter.18. The device of claim 16 , wherein the water soluble material is a globular serum protein having an approximate molecular weight of between 65-70 kD.19. The device of claim 16 , wherein the water soluble material comprises a serum protein having at least 90% identity to SEQ ID NO: 1.20. The device of claim 16 , wherein the water soluble material is human serum albumin.21. The device of claim 16 , wherein the multi-part drug layer is formulated as a single formulation and applied after the primer layer has been applied to a surface of the balloon catheter.24. The device of claim 16 , wherein the macrocyclic triene compound is rapamycin claim 16 , everolimus claim 16 , zotarolimus claim 16 , Biolimus or temsirolimus.25. The device of claim 16 , wherein the multi-part drug layer contains one of tacrolimus claim 16 , paclitaxel claim 16 , docetaxel claim 16 , analogs thereof or mixtures thereof.26. The device of claim 16 , wherein polymer-free excipient is a linear fatty alcohol or fatty aldehyde or a fatty acid or a nonionic surfactant containing at least 12 carbon atoms.27. The device of claim 16 , wherein polymer-free excipient of the second part of the multi- ...

Polymer-Free Drug Eluting Vascular Stents

This application relates generally to the field of implants and more specifically to drug eluting vascular stents and methods of making and using same. Specifically, this technology relates to controlled release of drug from an implant and particular from a stent without the presence of polymer or alteration of the implant surface. 115.-. (canceled)16. An implant for use in delivering at least one therapeutic agent to a target , comprising:(a) an implant, preferably capable of radial expansion; and(b) a coating layer, wherein the coating layer is formulated with at least one polymer-free excipient and at least one therapeutic agent, wherein the at least one therapeutic agent is an antiproliferative agent, wherein the coating layer is applied to the implant surface.17. The implant of claim 16 , wherein the at least one therapeutic agent is a macrocyclic triene immunosuppressive compound.18. The implant of claim 16 , wherein the implant is a drug eluting stent.19. The implant of claim 16 , wherein the implant body has a surface that is topographically smooth and/or wherein the surface has no reservoirs and contains a smooth surface free of any texturing or pores.20. The implant of claim 16 , wherein the implant is devoid of any surface modification that would result in a drug reservoir at more than one point on the implant body surface.21. The implant of claim 16 , wherein the coating layer is comprised of rapamycin claim 16 , everolimus claim 16 , zotarolimus claim 16 , Biolimus claim 16 , temsirolimus claim 16 , tacrolimus or analogs thereof.22. The implant of claim 16 , wherein the coating layer is comprised of paclitaxel claim 16 , docetaxel or analogs thereof.23. The implant of claim 16 , wherein the at least one polymer-free excipient is selected from the group consisting of a saturated or unsaturated fatty alcohol claim 16 , saturated or unsaturated fatty aldehyde or saturated or unsaturated fatty acid.24. The implant of claim 16 , further wherein the at least ...

PARENTERAL FORMULATION MATERIALS AND METHODS FOR 40-O-CYCLIC HYDROCARBON ESTERS AND RELATED STRUCTURES

This application relates generally to the field of drug treatment paradigms based on specifically formulated compounds for use in targeted therapy or disease prevention. Specifically, this technology provides for compositions and methods for treating, stabilizing, preventing or delaying disease conditions through administration of highly lipophilic compositions with a globular serum protein in combination with other pharmaceutical compositions. 111.-. (canceled)15. The drug formulation of claim 12 , wherein the macrocyclic triene immunosuppressive compound is one selected from the group consisting of rapamycin claim 12 , everolimus claim 12 , zotarolimus claim 12 , biolimus claim 12 , novolimus claim 12 , myolimus claim 12 , temsirolimus and derivatives related thereto.16. The drug formulation of claim 12 , wherein the at least one water soluble solubilizer is selected from the group comprising or consisting of ethanol claim 12 , propylene glycol claim 12 , polyoxyethylene sorbitan ester claim 12 , polyethylene glycol 200 claim 12 , polyethylene glycol 300 claim 12 , polyethylene glycol 400 claim 12 , and any combinations thereof.17. The drug formulation of claim 12 , wherein the water soluble polymer is a globular serum protein having an approximate molecular weight of between 65-70 kD.18. The drug formulation according to claim 17 , wherein the globular serum protein is a human serum protein having at least 90% homology to SEQ ID NO:1.191. An injectable aqueous solution comprising the formulation of any of the claim for use in parenteral administration to an individual in need thereof.21. The method of claim 20 , wherein the method does not comprise a particular step of forming nanoparticles claim 20 , in particular spherical uniformly sized regular nanoparticles of the macrocyclic triene immunosuppressive compound.221. A kit containing the first claim 20 , the second and the third components of claim in pre-weighed and/or premixed combinations thereof and in ...

Drug-delivery endovascular stent and method for treating restenosis

A radially expandable, endovascular stent designed for placement at a site of vascular injury, for inhibiting restenosis at the site, a method of using, and a method of making the stent. The stent includes a radially expandable body formed of one or more metallic filaments and a liquid-infusible mechanical anchoring layer attached to or formed in outer surface of the filaments. A drug coating in the stent is composed of a substantially polymer-free composition of an anti-restenosis drug, and has a substratum infused in the anchoring layer and a substantially continuous surface stratum of drug that is brought into direct contact with the vessel walls at the vascular site. Thus, the rate of release of the anti-restenosis drug from the surface stratum into said vascular site is determined solely by the composition of said drug coating.

Drug-delivery endovascular stent and method of use

An improvement in drug-eluting stents, and method of their making are disclosed. The surface of a metal stent is roughened to have a surface roughness of at least about 20 μin (0.5 μm) and a surface roughness range of between about 300-700 μin (7.5-17.5 μm). The roughened stent surface is covered with a polymer-free coating of a limus drug, to a coating thickness greater than the range of surface roughness of the roughened stent surface.

Fluid sample analyte collector and calibration assembly

A fluid sample collector, sensing, and calibration device contains a collector like a syringe, with one or more analyte sensors, and a calibrator for calibrating the sensor. These can be pre-assembled and are particularly adapted to be disposable after a single use; the analyte sensor may be connected to a self-contained monitoring instrument or analyzer which processes the signals from the sensor and displays the information to the operator.

Sensor assembly for measuring analytes in fluids

A sensor assembly for measuring analytes in fluids, e.g., blood, is described. The sensor assembly comprises a housing in the form of a flow-through cell containing one or more microsensors the housing disposed on the distal end of a hypodermic syringe.

Portable analyte measuring system for multiple fluid samples

A portable, ready-for-use analyte measuring device is provided for the measurement of multiple sequential fluid samples. The device has a disposable cartridge, a calibrating fluid external to the cartridge and an analyzer. The cartridge has a housing, inlet for introduction of fluids into the housing, flow cell in fluid connection with the inlet, a waste collection area or reservoir in fluid connection to receive fluids from the flow cell, and at least one flow control means in fluid connection with the reservoir. The flow cell has a flow-through channel with one or more hydrated sensors arranged along the channel that has fluid therein. Also the flow cell has one or more spaced-apart reference electrode containment spaces in conductive contact with a contained quantity of reference fluid for the number of multiple sequential tests for the cartridge. The reference electrode containment space is spaced apart from but in conductive relation with the one or more sensors. The flow cell also has an electric circuit attached for electrical conduction to the one or more sensors and reference electrode and which is electrically isolated from the fluid in the channel. The multi-test device also has signal conveyor connected to the electric circuit of the flow cell to transmit signals responsive to the fluids contacting the sensors to the analyzer. Both the cartridge and the calibrating fluid are associated with an encoded information carrier for sensor performance parameters and calibrant analyte concentrations for inputting into the encoded information reader of the analyzer.

Rapamycin 40-O-cyclic hydrocarbon esters, compositions and methods

A new class of rapamycin 40-O-cyclic hydrocarbon esters is disclosed. The 40-O position of the rapamycin ester has the form 40-O-R, where R is C(O)-(CH

Drug-delivery endovascular stent and method of use

A radially expandable, endovascular stent designed for placement at a site of vascular injury, for inhibiting restenosis at the site, a method of using, and a method of making the stent. The stent includes a radially expandable body formed of one or more metallic filaments where at least one surface of the filaments has a roughened or abraded surface. The stent may include a therapeutic agent on the abraded surface.

Drug-delivery endovascular stent and method for treating restenosis

An endovascular stent for placement at a vascular injury site for inhibiting restenosis at the site is provided, the stent comprising a structural member or body formed of one or more filaments and carried on the stent-body filament(s) a drug-release coating composed of (i) 20-70 weight percent polymer substrate and (ii) 30-80 weight percent of a macrocyclic triene immunosuppressive compound, wherein both the stent body and coating substrate are formed from a bioerodable polymer.

Drug-delivery endovascular stent and method for treating restenosis

An intravascular stent and method for inhibiting restenosis, following vascular injury, is disclosed. The stent has an expandable, linked-filament body and a drug-release coating formed on the stent-body filaments, for contacting the vessel injury site when the stent is placed in-situ in an expanded condition. The coating releases, for a period of at least 4 weeks, a restenosis-inhibiting amount of a monocyclic triene immunosuppressive compound having an alkyl group substituent at carbon position 40 in the compound. The stent, when used to treat a vascular injury, gives good protection against clinical restenosis, even when the extent of vascular injury involves vessel overstretching by more than 30% diameter. Also disclosed is a stent having a drug-release coating composed of (i) 10 and 60 weight percent poly-dl-lactide polymer substrate and (ii) 40-90 weight percent of an anti-restenosis compound, and a polymer undercoat having a thickness of between 1-5 microns.

Drug-delivery endovascular stent

An endovascular stent for placement at a vascular injury site for inhibiting restenosis at the site is provided, the stent comprising a structural member or body formed of one or more filaments and carried on the stent-body filament(s), a drug-release coating composed of (i) 20-70 weight percent polymer substrate and (ii) 30-80 weight percent of a macrocyclic triene immunosuppressive compound, wherein the coating substrate comprises a polylactic acid polymer.

Sensor assembly for measuring analytes in fluids

Abstract of the Disclosure A sensor assembly for measuring analytes in fluids, e.g., blood, is described. The sensor assembly comprises a housing in the form of a flow-through cell containing one or more microsensors the housing disposed on the distal end of a hypodermic syringe.

Sterilizable Hermetically-Sealed Substantially Glass Container and Method for Producing the Container

A hermetically sealed vial for liquids is provided by the present invention. The liquid can be a calibrant or a reference fluid for gas analysis where the liquid has dissolved gas or medication or medicaments. The vial is a glass container means with at least one opening. The dimensions of the opening range from that which is just effective for the addition and removal of fluids to that which is the smallest side of the container. A flange circumferentially extends about the opening. The vial has the liquid that does not fill the vial to leave room for a head space. The head space is present in an amount of the volume percent of the vial ranging from 1 to 99 compared to the amount of the liquid. The vial is sealed with an air impermeable bilaminate seal comprised of an adhesive polymer contacting the vial and a metal surface facing externally from the vial. Before the vial is sealed by heat or induction sealing a securing means like a cap or chemical coupling agents are used to hold the seal on the vial. When the cap is a snap cap a gasket can be present between the cap and the seal. The vials can be sterilized and processed as a plurality of vials during heat and induction sealing and optionally sterilization depending on the application.

method for producing a radially expandable endovascular stent and radially expandable endovascular stent

método para produzir um stent endovascular radialmente expansível e stent endovascular radialmente expandível. um stent endovascular radialmente expandível projetado para colocar em um local de lesão vascular, para inibir restenose no local, um método de utilizar, e um método de fazer o stent. o stent inclui um corpo radialmente expandível formado de um ou mais filamentos metálicos onde pelo menos uma superfície dos filamentos tem uma superfície encrespada ou desgastada. o stent pode incluir um agente terapêutico na superfície desgastada. method for producing a radially expandable endovascular stent and radially expandable endovascular stent. a radially expandable endovascular stent designed to place at a site of vascular injury, to inhibit restenosis at the site, a method of utilizing, and a method of making the stent. the stent includes a radially expandable body formed from one or more metallic filaments where at least one surface of the filaments has a crimped or abraded surface. the stent may include a therapeutic agent on the eroded surface.

Rapamycin 40-O-cyclic hydrocarbon esters, compositions and methods

A new class of rapamycin 40-O-cyclic hydrocarbon esters is disclosed. The 40-O position of the rapamycin ester has the form 40-O-R, where R is C(O)-(CH

Drug-releasing vascular stent

Una endoprótesis vascular para colocar en un lugar de lesión vascular con el fin de inhibir allí la restenosis, compuesta por un cuerpo tubular expandible de forma radial formado de un enrejado de filamentos conectados, y donde cada filamento tiene regiones superior y lateral y una superficie interna, y por una cubierta liberadora de fármaco formada por un sustrato de polímero de ácido poliláctico que contiene un fármaco trieno macrocíclico inhibidor de la restenosis; la capa mencionada se aplica como un compuesto líquido que cubre las regiones superior y lateral, pero no las superficies internas, de los filamentos mencionados. A stent to place at a site of vascular injury to inhibit restenosis there, consisting of a radially expandable tubular body formed of a lattice of connected filaments, and where each filament has upper and lateral regions and an internal surface , and by a drug-releasing shell formed by a polylactic acid polymer substrate containing a restenosis-inhibiting macrocyclic triene drug; The mentioned layer is applied as a liquid compound that covers the upper and lateral regions, but not the internal surfaces, of the mentioned filaments.

Drug-delivery endovascular stent and method for treating restenosis

An intravascular stent and method for inhibiting restenosis, following vascular injury, is disclosed. The stent has an expandable, linked-filament body and a drug-release coating formed on the stent-body filaments, for contacting the vessel injury site when the stent is placed in-situ in an expanded condition. The coating releases, for a period of at least 4 weeks, a restenosis-inhibiting amount of the macrocyclic triene immunosuppressive compound everolimus. The stent, when used to treat a vascular injury, gives good protection against clinical restenosis, even when the extent of vascular injury involves vessel overstretching by more than 30% diameter. Also disclosed is a stent having a drug-release coating composed of (i) 10 and 60 weight percent poly-dl-lactide polymer substrate and (ii) 40-90 weight percent of an anti-restenosis compound, and a polymer undercoat having a thickness of between 1-5 microns.

Drug-delivery endovascular stent and method for treating restenosis

Rapamycin 40-o-cyclic hydrocarbon esters, compositions and methods

A new class of rapamycin 40-O-cyclic hydrocarbon esters is disclosed having the structure (see above formula) The 40-O position of the rapamycin ester has the form 40-O-R, where R is C(O)-(CH2)n-X, n is 0, 1 or 2, and X is a cyclic hydrocarbon having 3-8 carbons, optionally containing one or more unsaturated bonds, and one or more linear (CH2)) and/or cyclic (X) carbon atoms may have an OH or halide group. Also disclosed are therapeutic compositions and methods that employ the novel analogs.

Intratumoral drug delivery materials and methods for treating breast cancer

This application relates generally to the field of drug delivery devices to augment standard radiation therapy and methods of making and using same. Specifically, this technology utilizes a controlled release of drug from a coated balloon for local intratumoral drug delivery to breast tissue to supplement or replace standard radiation therapy.

Drug-delivery endovascular stent and method of use

A radially expandable, endovascular stent designed for placement at a site of vascular injury, for inhibiting restenosis at the site, a method of using, and a method of making the stent. The stent includes a radially expandable body formed of one or more metallic filaments where at least one surface of the filaments has a roughened or abraded surface. The stent may include a therapeutic agent on the abraded surface.

Drug-Delivery Endovascular Stent And Method For Treating Restenosis

There is provided an endovascular stent for placement at a vascular injury site, for inhibiting restenosis at the site, comprising a radially expandable, tubular body formed of a lattice of connected filaments, each filament having top, edge and bottom support surfaces, and a drug-release coating layer containing a restenosis-inhibiting drug, said layer coating only on the top and at least a portion of the side surfaces, but not the inside surfaces, of said filaments. There is also provided a method of forming the aforementioned stent.

Drug-releasing vascular stent

Una endoprótesis vascular (20) para colocar en un lugar de lesión vascular para que desprenda un fármaco trieno macrocíclico a lo largo de un período largo tras colocar allí la endoprótesis; y la endoprótesis comprende un cuerpo formado de filamentos metálicos (24,26,28,30) con regiones superior, lateral e interna en su superficie y una cubierta biodegradable liberadora de fármaco (32) que cubre los filamentos formados de un polímero que contiene el fármaco trieno macrocíclico para su liberación de la cubierta; caracterizada en que la endoprótesis comprende una capa de imprimación (34) con un espesor entre 1 y 5 μm y una cubierta (32) formada sobre ella solo en las regiones superior y lateral de la superficie de la endoprótesis con un espesor entre 3 y 20 μm y compuesta de entre un 40 y 80% del peso del fármaco trieno macrocíclico y de entre el 20 y 60% del peso del polímero de poli-l-láctico o poli-dlláctico. A stent (20) to be placed at a site of vascular injury to release a macrocyclic triene drug over a long period of time after the stent has been placed there; and the stent comprises a body formed of metallic filaments (24,26,28,30) with upper, lateral and internal regions on its surface and a biodegradable drug-releasing covering (32) that covers the filaments formed of a polymer containing the macrocyclic triene drug for release from the shell; characterized in that the stent comprises a primer layer (34) with a thickness between 1 and 5 μm and a cover (32) formed on it only in the upper and lateral regions of the surface of the stent with a thickness between 3 and 20 μm and composed of between 40 and 80% of the weight of the macrocyclic triene drug and between 20 and 60% of the weight of the poly-l-lactic or poly-dlactic polymer.

Reference solution container having improved gas retention

A reference solution container (100) for an analyzer (300) for measuring gas and/or electrolyte levels in a fluid comprises a vessel or a bag containing the reference solution. The container also includes a self-sealing fluid port (104) for repeatedly accessing the reference solution in the vessel by a fluid carrying device external to the container. The partial pressure of each gas in the reference solution within the vessel is maintained at a substantially constant level.

Drug-delivery endovascular stent and method of use

Drug-delivery endovascular stent and method of use

An improvement in drug-eluting stents, and method of their making are disclosed. The surface of a metal stent is roughened to have a surface roughness of at least about 20 μin (0.5 μm) and a surface roughness range of between about 300-700 μin (7.5-17.5 μm). The roughened stent surface is covered with a polymer-free coating of a limus drug, to a coating thickness greater than the range of surface roughness of the roughened stent surface.

Polymer compositions containing a macrocyclic triene compound

A polymer composition for use in delivering a macrocyclic triene compound to a subject is described. The polymer composition is comprised of a polymer substrate containing as the macrocyclic triene compound a 40-0-hydroxy alkyl rapamycin derivative, where the alkyl group contains between 7-11 carbon atoms. The composition is useful for treating any condition responsive to rapamycin or everolimus, and methods of treatment using the polymer composition are described.

Rapamycin 40-o-cyclic hydrocarbon esters, compositions and methods

A new class of rapamycin 40-O-cyclic hydrocarbon esters is disclosed having the structure (see above formula) The 40-O position of the rapamycin ester has the form 40-O-R, where R is C(O)-(CH2)n-X, n is 0, 1 or 2, and X is a cyclic hydrocarbon having 3-8 carbons, optionally containing one or more unsaturated bonds, and one or more linear (CH2)) and/or cyclic (X) carbon atoms may have an OH or halide group. Also disclosed are therapeutic compositions and methods that employ the novel analogs.

Sterilizable hermetically-sealed substantially glass container and method for producing the container

A hermetically sealed vial for liquids is provided by the present invention. The liquid can be a calibrant or a reference fluid for gas analysis where the liquid has dissolved gas or medication or medicaments. The vial is a glass container means with at least one opening. The dimensions of the opening range from that which is just effective for the addition and removal of fluids to that which is the smallest side of the container. A flange circumferentially extends about the opening. The vial has the liquid that does not fill the vial to leave room for a head space. The head space is present in an amount of the volume percent of the vial ranging from 1 to 99 compared to the amount of the liquid. The vial is sealed with an air impermeable bilaminate seal comprised of an adhesive polymer contacting the vial and a metal surface facing externally from the vial. Before the vial is sealed by heat or induction sealing a securing means like a cap or chemical coupling agents are used to hold the seal on the vial. When the cap is a snap cap a gasket can be present between the cap and the seal. The vials can be sterilized and processed as a plurality of vials during heat and induction sealing and optionally sterilization depending on the application.

Covered stent for local drug delivery

The present invention relates generally to an endoprosthesis for maintaining patency of a body vessel, e.g., a stent, in a basically tubular configuration comprised of a structural lattice with a mesh covering which is capable of storing releasing one or more drugs to and penetrating into surrounding tissue.

Drug-delivery endovascular stent and method of use

An improvement in drug-eluting stents, and method of their making are disclosed. The surface of a metal stent is roughened to have a surface roughness of at least about 20 µin (0.5 µm) and a surface roughness range of between about 300-700 µin (7.5-17.5 µm). The roughened stent surface is covered with a polymer-free coating of a limus drug, to a coating thickness greater than the range of surface roughness of the roughened stent surface.

Drug-delivery endovascular stent and method for treating restenosis

An endovascular stent for placement at a vascular injury site for inhibiting restenosis at the site is provided, the stent comprising a structural member or body formed of one or more filaments and carried on the stent-body filament(s), a drug-release coating composed of (i) 20-70 weight percent polymer substrate and (ii) 30-80 weight percent of a macrocyclic triene immunosuppressive compound, wherein the coating substrate comprises a polylactic acid polymer.

Microsphere drug coated medical devices, materials and methods

The field of materials and manufacturing methods involving single or multi-solvent, excipient and polymer-free drug coating formulations for production of microsphere coated drug delivery techniques.

Macrocyclic triene immunosuppressive compounds for perivascular medical treatment of vascular access fistulas, grafts and other vascular conditions

This application relates generally to the field of treatment or prevention of "open" vascular surgical interventions with administration of a macrocyclic triene immunosuppressive compound in order to reduce or eliminate stenotic and/or vascular cancer conditions.

Synthesis and characterization of cyclic hydrocarbon esters of everolimus

This application relates generally to the field of synthesis, formulations and perivascular treatment methods involving cyclic ester derivatives of everolimus.

Intratumoral drug delivery materials and methods for treating breast cancer

Materials and Methods for Treating Viral and Other Medical Conditions

This application relates generally to the field of drug treatment paradigms based on specifically formulated compounds for use in targeted therapy or disease prevention. Specifically, this technology provides for compositions and methods for treating, stabilizing, preventing or delaying disease conditions related to viral infections and other inflammatory conditions.

Arzneimittel abgebender endovaskulärer stent

Materials and methods for treating viral and other medicinal conditions

This application relates generally to the field of drug treatment paradigms based on specifically formulated compounds for use in targeted therapy or disease prevention. Specifically, this technology provides for compositions and methods for treating, stabilizing, preventing or delaying disease conditions related to viral infections and other inflammatory conditions.

Polymer-free drug eluting vascular stents

This application relates generally to the field of implants and more specifically to drug eluting vascular stents and methods of making and using same. Specifically, this technology relates to controlled release of drug from an implant and particular from a stent without the presence of polymer or alteration of the implant surface.

Intracranial drug delivery materials and methods

This application relates generally to the field of minimally invasive delivery of therapeutic agents. Specifically, the present invention provides for materials and methods directed to minimally invasive, targeted delivery of agents such as drugs, penetrants, blood barrier augmentation agents or other compounds to certain localized brain regions through the use of delivery balloon catheters.

42-o-alkoxyalkyl rapamycin derivatives and compositions comprising same

42-O-alkoxyalkyl derivatives of rapamycin having biological activity are described. Compositions and delivery devices comprising the 42-O-alkoxyalkyl rapamycin derivatives are also disclosed.

Intratumoral drug delivery materials and methods for treating breast cancer

Generally, the invention is in relation to the field of drug delivery devices to augment standard radiation therapy and methods of making and using same. Specifically, this technology utilizes a controlled release of drug from a coated balloon for local intratumoral drug delivery to breast tissue to supplement or replace standard radiation therapy.

Intratumoral drug delivery materials and methods for treating breast cancer

Pharmaceutical microsphere compositions and methods

This application relates generally to the field of materials and manufacturing methods involving microsphere compositions and pharmaceutical applications related thereto.

Microsphere drug coated medical devices and methods

Microsphere drug coated medical devices and methods

This application relates generally to the field of materials and manufacturing methods involving single or multi-solvent, excipient and polymer-free drug coating formulations for production of microsphere coated drug delivery techniques.

Microsphere drug coated medical devices and methods