Expansible Biocompatible Coats Comprising a Biologically Active Substance

• US 20110046724A1
• Filed: 03/31/2009
• Published: 02/24/2011
• Est. Priority Date: 03/31/2008
• Status: Abandoned Application

• Current Assignee: Avidal Vascular GmbH (AVIDAL Distribution GmbH)
• Original Assignee: Avidal Vascular GmbH (AVIDAL Distribution GmbH)
• Inventors: Heilmann, Torsten, Richter, Christian, Post, Sabine
• Application Number:
  US12/934,762
• Publication Number:
  US 20110046724A1
• Time in Patent Office: Days
• US Class Current: 623/1.46
• CPC Class Codes: A61B 17/12109 in a blood vessel
• CPC Class Codes: A61B 17/12136 Balloons
• CPC Class Codes: A61B 2017/00526 Methods of manufacturing
• CPC Class Codes: A61B 2017/00893 pharmaceutically effective
• CPC Class Codes: A61F 2/82 Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents stent-grafts for tubular structures of the body other than blood vessels A61F2/04; stent-grafts for blood vessels A61F2/07; instruments specially adapted for placement or removal of stents or stent-grafts A61F2/95; for closing wounds, or holding wounds closed A61B17/04 - A61B17/115; dilators A61M29/00
• CPC Class Codes: A61F 2250/0067 Means for introducing or releasing pharmaceutical products into the body
• CPC Class Codes: A61F 2250/0068 the pharmaceutical product being in a reservoir
• CPC Class Codes: A61L 2300/00 Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
• CPC Class Codes: A61L 29/14 Materials characterised by their function or physical properties , e.g. lubricating compositions
• CPC Class Codes: A61L 29/146 Porous materials, e.g. foams or sponges
• CPC Class Codes: A61L 29/16 Biologically active materials, e.g. therapeutic substances A61L29/048 takes precedence
• CPC Class Codes: A61L 31/14 Materials characterised by their function or physical properties , e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
• CPC Class Codes: A61L 31/146 Porous materials, e.g. foams or sponges
• CPC Class Codes: A61L 31/16 Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence
• CPC Class Codes: A61M 2025/0056 provided with an antibacterial agent, e.g. by coating, residing in the polymer matrix or releasing an agent out of a reservoir
• CPC Class Codes: A61M 2025/0057 Catheters delivering medicament other than through a conventional lumen, e.g. porous walls or hydrogel coatings
• CPC Class Codes: A61M 2025/1031 Surface processing of balloon members, e.g. coating or deposition; Mounting additional parts onto the balloon member's surface
• CPC Class Codes: A61M 2025/105 having a balloon suitable for drug delivery, e.g. by using holes for delivery, drug coating or membranes
• CPC Class Codes: A61M 25/0045 multi-layered, e.g. coated coating materials A61L29/08
• CPC Class Codes: A61M 25/10 Balloon catheters A61M25/0125 takes precedence; embolectomy A61B17/22032; retractors A61B17/02; inflatable balloons for placing stents or stent-grafts A61F2/958 ; stomach balloons for treatment of obesity A61F5/0003; oesophagal tubes A61J15/00
• CPC Class Codes: A61M 25/1036 : Making parts for balloon catheter systems, e.g. shafts or distal ends A61M25/1029 takes precedence
• CPC Class Codes: A61M 25/104 : used for angioplasty
• CPC Class Codes: A61N 1/375 : Constructional arrangements, e.g. casings
• CPC Class Codes: A61N 1/37512 : Pacemakers
• CPC Class Codes: A61P 9/00 : Drugs for disorders of the cardiovascular system
• CPC Class Codes: B05D 3/12 : by mechanical means

Abstract

The present invention relates to an expansible hollow part, having at least one opening, which consists of an elastic biocompatible material and which comprises at least one biologically active substance and, optionally at least one matrix compound. The invention also provides a method of producing said expansible hollow part, a medical device covered at least partially with said hollow part, a kit-of-parts comprising said hollow part of the invention and the use of said hollow part as a therapeutic device and for protecting a medical device.

Claims

1. An expansible hollow part, having at least one opening, which consists of an elastic biocompatible material and which comprises at least one biologically active substance and, optionally, at least one matrix compound, wherein the expansible hollow part is porous and/or comprises micro-cavities in its surface.

2. The expansible hollow part of claim 1, wherein the hollow part is expansible to at least 110% of the circumference of its non-expanded state.

3. The expansible hollow part of claim 1, wherein the hollow part has a wall thickness of smaller than 1 mm in its non-expanded state.

4. The expansible hollow part of claim 1, wherein the surface of the hollow part is substantially impermeable to liquid and/or gas.

5. The expansible hollow part of claim 1, wherein the micro-cavities are elongated.

6. The expansible hollow part of claim 5, wherein the elongated micro-cavities are selected from the group consisting of crescent-shaped furrows, sinuous furrows, circular furrows, elliptical furrows, furrows comprising one or more bends, straight furrows, bifurcated furrows and combinations thereof.

7. The expansible hollow part of claim 5, wherein the elongated micro-cavities have a length of not more than 2 mm.

8. The expansible hollow part of claim 1, wherein the depth of the micro-cavities is between 5 μ

m and 500 μ

m.

9. The expansible hollow part of claim 1, wherein the micro-cavities are tilted with respect to the surface of the hollow part.

10. The expansible hollow part of claim 1, wherein the micro-cavities are tilted in direction of the longitudinal axis of the expansible hollow part.

11. The expansible hollow part of claim 1, wherein the micro-cavities are substantially closed when the expansible hollow part is in its non-expanded state.

12. The expansible hollow part of claim 1, wherein the micro-cavities open up when the expansible hollow part is expanded.

13. The expansible hollow part of claim 1, wherein the micro-cavities form fringes protruding from the surface of the expansible hollow part when said expansible hollow part is expanded.

14. The expansible hollow part of claim 1, wherein the expansible hollow part has an inner diameter smaller than 1 cm in its non-expanded state.

15. The expansible hollow part of claim 1, wherein more than 50% of the biologically active substance, and optionally of said matrix compound is located in said micro-cavities.

16. The expansible hollow part according to claim 1, wherein the elastic biocompatible material consists, comprises or essentially consists of a material selected from the group consisting of:

natural rubber, polyisoprene, a copolymer of isobutylene and isoprene, a halogenated butyl rubber, a polybutadiene, a styrene-butadiene rubber, a copolymer of polybutadiene and acrylonitrile, a hydrogenated nitrile rubber, a chloroprene rubber, a polychloroprene, latex, a neoprene, a baypren, latex, parylene, polyvalerolactone, poly-ε

-decalactone, polylactic acid, polyglycol acid, polylactide, polyglycolide, co-polymer of polylactide and polyglycolide, poly-ε

-caprolactone, polyhydroxy butyric acid, polyhydroxybutyrate, polyhydroxyvalerate, polyhydroxybutyrate-co-valerate, poly(1,4-dioxan-2,3-dione), poly(1,3-dioxan-2-one), poly-para-dioxanone, polyanhydride, polymaleicacidanhydride, polyhydroxymethacrylate, fibrin, polycyanoacrylate, polycaprolactondimethylacrylate, poly-β

-maleic acid, polycaprolactonbutylacrylate, multiblockpolymers made of oligocaprolactondiole and oligodioxanondiole, polyetherestermultiblockpolymers made from PEG and polybutylenterephtalate, polypivotolactone, poly-glycolic acid trimethylcarbonate polycaprolactonglycolide, poly(g-ethylglutamate), poly(dth-iminocarbonate), poly(dte-co-dt-carbonat), poly(bisphenol A-iminocarbonate), polyorthoester, poly-glycolic acid-trimethylcarbonate, polytrimethylcarbonate polyiminocarbonate, poly(n-vinyl)-pyrrolidone, polyvinylalcohols, polyesteramide, glycolized polyester, polyphosphoester, polyphosphazene, poly(p-carboxyphenoxy)propane], polyhydroxypentanoic acid, polyethylenoxidpropylenoxid, polyurethane, polyurethane comprising amino acids, polyetherester like polyethyleneoxide, polyalkeneoxalate, polyorthoester, lipids, carrageenane, fibrinogen, starch, collagene, protein-based polymers, polyaminoacids, zein, polyhydroxyalkanoate, pectic acid, actinic acid, carboxymethylsulfate, albumine, hyaluronic acid, chitosane, heparanesulfate, heparine, chondroitinsulfate, dextrane, β

-cyclodextrine, copolymers comprising PEG and polypropyleneglycole, gummi arabicum, guar, gelatine, collagen-n-hydroxysuccinimide, phospholipids, polyacrylic acid, polyacrylate, polymethylmethacrylate, polybutylmethacrylate, polyacrylamide, polyacrylonitrile, polyamide, polyetheramide, polyethyleneamine, polyimide, polycarbonate, polycarbourethane, polyvinylketone, polyvinylhalogenide, polyvinylidenhalogenide, polyvinylether, polyisobutylene, aromatic compounds comprising a polyvinyl functional group, polyvinylester, polyvinylpyrollidone, polyoxymethylene, polytetramethyleneoxide, polyethylen, polypropylen, polytetrafluorethylen, polyetherurethane, silicon-polyetherurethane, silicon-polyurethane, silicon-polycarbonat-urethane, polyolefin-elastomers, epdm-rubber, fluorosilicone, carboxymethylchitosane, polyaryletheretherketone, polyetheretherketone, polyethylenterephtalate, polyvalerate, carboxymethylcellulose, cellulose, rayon, rayontriacetate, cellulosenitrate, celluloseacetate, hydroxyethylcellulose, cellulosebutyrate, celluloseacetatebutyrate, ethylvinylacetate, polysulfone, epoxy-resin, abs-resin, silicone like polysiloxane, polydimethylsiloxane, polyvinylhalogens, cellulose-ether, cellulose-triacetate, copolymers mixtures and derivatives thereof.

17. The expansible hollow part according to claim 1, wherein the biologically active substance is selected from the group consisting of:

a vasoconstrictor, a vasodilatator, a muscle relaxant, an antimycotic, a cytotoxic agent, a prodrug of a cytotoxic agent, a virustatic, a physiological or pharmacological inhibitor of mitogens, a cytostatic, a chemotherapeutic, an adrenocorticostatic, a β

-adrenolytic, an androgen or antiandrogen, an antianemic, an anabolic, an anaesthetic, an analeptic, an antiallergic, an antiarrhythmic, an antiarterosclerotic, an antibiotic, an antifibrinolytic, an anticonvulsive, an angiogenesis inhibitor, an anticholinergic, an enzyme, a coenzyme, an antihistaminic, an antihypertensive, an antihypotensive, an anticoagulant, an antiseptic, an antihemorrhagic, a beta-receptor antagonist, a calcium channel antagonist, an antimyasthenic, an antiphlogistic, an antipyretic, a glucocorticoid, a haemostatic, an immunoglobuline or its fragment, a chemokine, a mitogen, a cell differentiation factor, a hormone, an immunosuppressant, an immunostimulant, a mineralcorticoid, a narcotic, a vector, a peptide, a (para)-sympathicomimetic, a (para)-sympatholytic, a protein, a cell, a sedating agent, a spasmolytic, a wound-healing substance, and combinations thereof.

18. The expansible hollow part according to claim 1, wherein the expansible hollow part comprises at least 0.5 μ

g of the biologically active substance per square millimetre surface in its non-expanded state.

19. The expansible hollow part according to claim 1, wherein the matrix compound is selected from a group consisting of polyvalerolactone, poly-ε

-decalactone, polylactic acid, polyglycolic acid, polylactide, polyglycolide, copolymers of polylactide and polyglycolide, poly-ε

-caprolactone, polyhydroxylbutyric acid, polyhydroxybutyrate, polyhydroxyvalerate, polyhydroxybutyrate-co-valerate, poly(1,4-dioxane-2,3-dione), poly(1,3-dioxane-2-one), poly-para-dioxanone, polyanhydride, polymaleicacidanhydride, polyhydroxymethacrylate, fibrin, polycyanoacrylate, polycaprolactondimethylacrylate, poly-b-maleic acid polycaprolactonbutylacrylate, multi-block polymers of oligocaprolactondiole and oligodioxanonediole, polyetherestermultiblockpolymers made of peg und polybutylene terephthalate, polypivotolactone, polyglycolic acid trimethylcarbonate polycaprolactonglycolide, poly(g-ethylglutamate), poly(dth-lminocarbonate), poly(dte-co-dt-carbonate), poly(bisphenol a-iminocarbonate), polyorthoester, polyglycolic acid trimethylcarbonate, polytrimethylcarbonate, polyiminocarbonate, poly(n-vinyl)-pyrrolidone, polyvinylalcohol, polyesteramide, glycolated polyester, polyphosphoester, polyphosphazene, poly[p-carboxyphenoxy)propane], polyhydroxypentanoic acid, polyethyleneoxidepropyleneoxide, polyurethane, polyurethane having amino acids in the backbone, polyetherester like polyethyleneoxide, polyalkeneoxalate, lipid, carrageenane, fibrinogen, starch, collagene, polymers comprising protein, protein, polyaminoacid, synthetic polyaminoacid, zein, polyhydroxyalkaneoate, pectic acid, actinic acid, carboxymethylsulfate, albumin, hyaluronic acid, chitosan und derivatives thereof, heparanesulfate und ist derivatives, heparine, chondroitinsulfate, dextrane, β

-cyclodextrine, copolymers of peg and polypropyleneglycol, gummi arabicum, guar, gelatine, collagen-n-hydroxysuccinimide, phospholipid, polyacrylic acid, polyacrylate, polymethyl methacrylate, polybutyl methacrylate, polyacrylamide, polyacrylonitrile, polyamide, polyetheramide, polyethyleneamine, polyimide, polycarbonate, polycarbourethane, polyvinylketone, polyvinylhalogenide, polyvinylidenhalogenide, polyvinylether, polyisobutylene, polyvinyl compounds, polyvinyl ester, polyvinylpyrollidone, polyoxymethylene, polytetramethylene oxid, polyethylene, polypropylene, polytetrafluoroethylene, polyetherurethane, silicone-polyetherurethane, silicone-polyurethane, silicone-polycarbonate-urethane, polyolefin, epdm-rubber, fluorosilicone, carboxymethylchitosane, polyaryletheretherketone, polyetheretherketone, polyethylene terephthalat, polyvalerate, carboxymethylcellulose, rayon, rayontriacetate, cellulose nitrate, cellulose acetate, hydroxyethylcellulose, cellulosebutyrate, celluloseacetatbutyrate, ethylvinylacetate, polysulfone, parylene, epoxy resin, abs-resin, silicone like polysiloxane, polydimethylsiloxane, polyvinylhalogene, cellulose ether, cellulose triacetate, chiosane, N,N-diethylnicotinamide, N-picolylnicotinamide, N-allylnicotinamide, sodium salicylate, 2-methacryloyloxyethyl phosphorylcholine, resorcinol, N,N-dimethylnicotinamide, N-methylnicotinamide, butylurea, pyrogallol, N-picolylacetamide, procaine HCl, nicotinamide, pyridine, 3-picolylamine, sodium ibuprofen, sodium xylenesulfonate, ethyl carbamate, 6-hydroxy-N,N-diethylnicotinamide, sodium p-toluenesulfonate, pyridoxal hydrochloride, 1-methyl-2-pyrrolidone, sodium benzoate, 2-Pyrrolidone, ethylurea, N,N-dimethylacetamide, N-methylacetamide, isoniazid, iopromide, a contrast dye, iobitridol, iohexyl, iomeprol, iopamidol, iopentol, iopromide, ioversol, ioxilan, iotrolan, iodixanol, ioxaglate, and combinations, derivatives and copolymers of combinations thereof.

27. A medical device covered at least partially by the expansible hollow part according to claim 1.

28. Medical device according to claim 27, wherein the medical device is selected form the group consisting of a stent, a balloon catheter, a probe, a prosthesis, an endoscope, a pace maker, a heart defibrillator and a perfusion catheter.

29. Medical device according to claim 28, wherein the medical device is a balloon catheter;

and wherein the expansible hollow part is covered at least partially by a stent.

30. Medical device according to claim 28, wherein the medical device is a stent;

and wherein the stent is on a balloon catheter.

31. Medical device according to claim 28, wherein the balloon catheter comprises a hot balloon, a cold balloon, an occlusion balloon, a valvuloplasty-balloon and/or a protection device.

32. Medical device according to claim 28, wherein the balloon catheter is a perfusion catheter which comprises a hot balloon or a cold balloon.

33. Medical device according to claim 28, wherein the balloon catheter and the expansible hollow part are connected to each other by at least one clamping piece.

34. Medical device according to claim 27, wherein the circumference of the medical device in its non-expanded state is greater than the inner circumference of the expansible hollow part in its non-expanded state.

35. A kit-of-parts comprising at least one expansible hollow part according to claim 1 and at least one medical device.

36. Kit-of-parts according to claim 35, wherein the medical device is selected from the group consisting of a stent, a balloon catheter, a probe, a prosthesis, an endoscope, a pace maker, a heart defibrillator and a perfusion catheter.

37. Kit-of-parts according to claim 35, wherein the circumference of the medical device in its non-expanded state is greater than the inner circumference of the expansible hollow part in its non-expanded state.

38. A method for treatment of a disease or a medical insufficiency comprising treating a subject with a disease or a medical insufficiency selected from the group consisting of a stenosis, a restenosis, a stricture, a defective bypass craft, a thrombosis, a dissection, a tumor, a calcification, an arteriosclerosis, an inflammation, an autoimmune response, a necrosis, an injured anastomosis, a lesion, an allergy, a wart, a hyperproliferation, an infection, a scald, an edema, a coagulation, a cicatrization, a burn, a frostbite and a lymphangitis, with a therapeutic device comprising the expansible hollow part according to claim 1.

39. The method of claim 38, wherein the therapeutic device comprises a balloon catheter.

20. Method of producing an expansible hollow part having at least one opening, which consists of an elastic biocompatible material and which comprises at least one biologically active substance and, optionally, at least one matrix compound, comprising the steps:

(a) expanding the expansible hollow part to at least 110% of its non expanded circumference, and,

(b) contacting the outer surface of the expansible hollow part with at least one biologically active substance and/or at least one matrix compound.

21. The method according to claim 20 further comprising at least one additional step selected from the steps consisting of:

(c) relaxing the expansible hollow part so that its circumference is smaller than the circumference of the expansible hollow part in step (a);

(d) cutting elongated micro-cavities into the elastic biocompatible material; and

(e) mechanically everting the expansible hollow part.

22. The method according to claim 21, wherein the steps (a) and (b) or (b) and (c) are carried out simultaneously.

23. The method according to claim 21, wherein

(i) step (e) is carried out before step (a) and/or after step (b) and/or after step (c);

(ii) steps (a) and (b) are carried out in that order;

(iii) steps (a), (d) and (b) are carried out in that order;

(iv) steps (e), (a) and (b), are carried out in that order;

or

(v) steps (b), (e), (b) are carried out in that order, whereby in the first step (b) a different biologically active substance is used than the second step (b).

24. The method according to claim 20, wherein the expansion in step (a) is carried out using an expansible medical device or a mechanical tool.

25. The method according to claim 20, wherein the expansible hollow part is a tubular structure, preferably having two open ends, and comprising a plurality of elongated micro-cavities that are selected from the group consisting of crescent-shaped furrows, sinuous furrows, circular furrows, elliptical furrows, furrows comprising one or more bends, straight furrows, bifurcated furrows and combinations thereof.

26. An expansible hollow part producible by the method of claim 20.

40. (canceled)