Medical stent provided with inhibitors of atp synthesis

• US 20090324682A1
• Filed: 08/30/2005
• Published: 12/31/2009
• Est. Priority Date: 08/30/2004
• Status: Abandoned Application

• Current Assignee: Interstitial Therapeutics
• Original Assignee: Interstitial Therapeutics
• Inventors: Popowski, Youri
• Application Number:
  US11/661,437
• Publication Number:
  US 20090324682A1
• Time in Patent Office: Days
• US Class Current: 424/426
• CPC Class Codes: A61K 31/352 condensed with carbocyclic rings, e.g. methantheline cannabinoids A61K31/658
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 9/0024 Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue compositions for intravenous administration, normal injectable solutions or dispersions for, e.g. subcutaneous administration A61K9/0019; brain implants A61K9/0085; (coated) prostheses, catheters or stents A61L
• CPC Class Codes: A61L 2300/432 Inhibitors, antagonists A61L2300/402 - A61L2300/43 take precedence
• CPC Class Codes: A61L 2300/602 Type of release, e.g. controlled, sustained, slow
• CPC Class Codes: A61L 2300/622 Microcapsules
• CPC Class Codes: A61L 2300/624 Nanocapsules
• CPC Class Codes: A61L 31/10 Macromolecular materials
• CPC Class Codes: A61L 31/16 Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence
• CPC Class Codes: A61P 35/00 Antineoplastic agents

Abstract

A stent provided with a composition having at least one type of inhibitor of ATP synthesis, optionally together with at least one inhibitor of the pentose phosphate pathway is disclosed. The medical stent is useful for treating stenosis and preventing restenosis in vascular ducts and for treating cancerous tumors present in ducts, resectioned cavities and scars and any disorder arising from the proliferation of cells in ducts or cavities.

Claims

1. A medical stent provided with a composition comprising at least one type of inhibitor of glycolysis and/or the TCA cycle.

2. A medical stent according to claim 1, wherein said composition further comprises at least one inhibitor of the pentose phosphate pathway, PPP.

3. A medical stent according to claims 1 or 2, wherein said composition further comprises at least one inhibitor of oxidative phosphorylation.

4. A medical stent according to any of claims 1 to 3, wherein said stent is provided with one or more cavities for containing and releasing said composition.

5. A medical stent according to any of claims 1 to 3, wherein said stent is at least partly made from a material which is biodegradable in situ.

6. A medical stent according to any of claims 1 to 5, wherein said stent comprises a magnesium based alloy.

7. A medical stent according to any of claims 1 to 3, wherein said stent is at least partly made from a material which is non-biodegradable in situ.

8. A medical stent according to any of claims 1 to 7, wherein said stent is at least partly provided with said composition.

17. A medical stent according to any of claims 1 to 8, a use according to claims 9 to 13, or a kit according to any of claims 14 to 16, wherein said composition further comprises one or more slow release agents to facilitate slow release of inhibitor.

18. A medical stent, use or a kit according to claim 17, wherein said slow release agent is any of magnesium alloys, poly(glycolic) acid, poly(lactic acid) or in general glycolic- and lactic acid based polymers, copolymers, poly caprolactones and in general, poly hydroxyl alkanoates, poly(hydroxy alcanoic acids), Poly(ethylene glycol), poly vinyl alcohol, poly (orthoesters), poly(anhydrides), poly(carbonates), poly amides, poly imides, poly imines, poly(imino carbonates), poly(ethylene imines), polydioxanes, poly oxyethylene (poly ethylene oxide), poly(phosphazenes), poly sulphones, lipids, poly acrylic acids, poly methylmethacrylate, poly acryl amides, poly acrylo nitriles (Poly cyano acrylates), poly HEMA, poly urethanes, poly olefins, poly styrene, poly terephthalates, poly ethylenes, poly propylenes, poly ether ketones, poly vinylchlorides, poly fluorides, silicones, poly silicates (bioactive glass), siloxanes (Poly dimethyl siloxanes), hydroxyapatites, lactide-capronolactone, natural and non natural poly aminoacids, poly β

-aminoesters, albumines, alginates, cellulose/cellulose acetates, chitin/chitosan, collagene, fibrine/fibrinogen, gelatine, lignine, proteine based polymers, Poly(lysine), poly(glutamate), poly(malonates), poly(hyaluronic acids), Poly nucleic acids, poly saccharides, poly(hydroxyalkanoates), poly isoprenoids, starch based polymers, copolymers thereof, linear, branched, hyperbranched, dendrimers, crosslinked, functionalised derivatives thereof, or hydrogels based on activated polyethyleneglycols combined with alkaline hydrolyzed animal or vegetal proteins.

19. A medical stent, kit or use according to any of claims 1 to 18, wherein at least one type of inhibitor of glycolysis and/or the TCA cycle is encapsulated a micro-capsule or nano-capsule.

20. A medical stent, kit or use to claim 19 wherein a nano-capsule comprises any of a copolymer poly(ethylene oxide) with poly(L-Lactic acid) or with poly(beta-benzyl-L-aspartate);

copolymer with poly(lactide-co-glycolide)-[(propylene oxide)-poly(ethylene oxide)];

polyphosphazene derivatives;

a poly(ethylene glycol) coated nanosphere;

a poly(isobutylcyanoacrylate) nanocapsules poly(gamma-benzyl-L-glutamate)/(poly(ethylene oxide);

chitosan-poly(ethylene oxide) nanoparticules;

o-carboxymethylate chitosan, or a solid lipid nanosphere (SLN).

21. A medical stent, kit or use according to claim 19 wherein a micro-capsule comprises any of chitosan;

a coated alginate microsphere;

an N-(aminoalkyl) chitosan microsphere;

a chitosan/calcium alginate bead, a poly(adipic anhydride) microsphere;

a gellan-gum bead;

a poly(D,L-lactide-co-glycolide) microsphere;

an alginate-poly-L-lysine microcapsule;

a crosslinked chitosan microsphere;

a chitosan/gelatin microsphere;

a crosslinked chitosan network bead with spacer groups;

an aliphatic polyester;

a 1,5-diozepan-2-one microsphere;

a D,L-dilactide microsphere;

a triglyceride liposphere;

a polyelectrolyte complexe of sodium alginate chitosan;

a polypeptide microcapsule, oran albumin microsphere.

22. A medical stent, kit or use according to any of claims 1 to 21, wherein at least one of said inhibitors is coupled to solubilising agent.

23. A medical stent, kit or use according to claim 22, wherein said solubilising agent is cholesterol or derivative thereof.

24. A medical stent, kit or use according to claim 23, wherein said cholesterol derivatives are any of cholesteryl-3-betahydroxybutyrate, cholesteryl-halogenated butyrate, cholesteryl-halogenated acetate, cholesteryl-halogenated aceto-acetate, cholesteryl-halogenated acetamide, cholesteryl-halogenated crotonate, cholesteryl-halogenated acetone, cholesteryl-halogenated citrate, or cholesteryl-halogenated oleate

25. A medical stent, kit or use according to claim 22, wherein said solubilising agent is vitamin A or derivative thereof.

26. A medical stent, kit or use according to claim 25, wherein derivative of vitamin A is formula (IV) or (V):

wherein R is selected from the group consisting of betahydroxybutyrate, halogenated butyrate, halogenated acetate, halogenated aceto-acetate, halogenated acetamide, halogenated crotonate, halogenated acetone, halogenated citrate, and halogenated oleate.

27. A medical stent, a kit or a use according to any of claims 1 to 26 wherein said inhibitor of glycolysis inhibits at least one enzyme from the group consisting of hexokinase, glucokinase, phosphoglucose isomerase, phosphofructokinase, aldolase, triose phosphate isomerase, glyceraldehyde 3-phosphate dehydrogenase, phosphoglycerate kinase, phosphoglyceromutase, enolase, pyruvate kinase, and lactate dehydrogenase.

28. A medical stent, a kit or a use according to claim 27 wherein said inhibitor of glycolysis is a hexose sugar modified by removal of the hydroxyl group or by the substitution of the hydroxyl group with halogen atom or thiol at:

C6 for inhibiting hexokinase,

C1 or C2 or C5 for inhibiting phosphoglucoisomerase

C3 and/or C4 for blocking aldolase, and/or

C2 or C3 for blocking glyceraldehyde 3P deshydrogenase, phosphoglycerate kinase, phosphoglycerate mutase, and enolase.

29. A medical stent, a kit or a use according to claim 27, wherein said inhibitor is any of 6-deoxy-6-fluoro-D-glucose, 6-deoxy-6-bromo-D-glucose, 6-deoxy-6-chloro-D-glucose, 6-O-methyl-D-glucose, 6-thio-D-glucose, 6-deoxy-D-glucose, C-6 modified or blocked derivatives of other hexose ring pyranoses, mannopyranoses, galactopyranoses, 6-deoxy-6-fluoro-D-glucose, 6-deoxy-6-bromo-D-mannose, 6-deoxy-6-chloro-D-mannose, 6-deoxy-6-fluoro-D-galactose, 6-deoxy-6-chloro-D-galactose, 6-deoxy-6-iodo-D-galactose, 6-deoxy-6-bromo-D-galactose, halogenated C-6 sugars gluconolactones, glucuronic acid, glucopyranoside, and their phosphate derivatives, glucoronides with halogenated glycosides at the C-1 position, C-2 substituted D-hexoses, 2-deoxy-2-halogeno-D-hexoses, 2-deoxy-2-fluoro-D-glucose, 2-chloro-2-deoxy-D-glucose, 2-bromo-D-glucose, 2-iodo-D-glucose, 2-deoxy-2,2-difluoro-D-arabino-hexose, 2-deoxy-2-fluoro-D-mannose, 2-deoxy-D-arabino-hexose, 2-Deoxy-2-fluoro-D-galactose, 1,6-anhydro-2-deoxy-2-fluoro-beta-D-glucopyranose, 1-6-anhydrosugar, 2-amino-2-deoxy-D-glucose, glucose amine, 2-amino-2-deoxy D-galactose, galactosamine, 2-amino-2-deoxy-D-mannose, mannosamine, 2-deoxy-2-fluoro-D-mannose, 2-deoxy-2-fluoro-D-galactose, 2-deoxy-D-arabino-hexose, 2-deoxy-2,2-difluoro-D-arabino-hexose, 2-deoxy-2-fluoro-D-glucose 1-Phosphate, 2-deoxy-2-fluoro-D-glucose 6-P, 2-deoxy-2-fluoro-D-glucose 1,6 biphosphate, 2-deoxy-2-fluoro-D-mannose 1-P, 2-deoxy-2-fluoro-D-mannose 6-P, 2-deoxy-2-fluoro-D-mannose 1,6-biphosphate, nucleotide diphosphate, uridine di-P, 1-2 deoxy-2-fluoro-D-glucose, C-2-halogen substituted, and NH3 substituted derivatives of D-Glucose 6-phosphate, 2-deoxy-2-fluoro-2-D-glucose-6-phosphate, 2-chloro-2-deoxy-D-glucose-6-phosphate, 2-deoxy-D-arabino-hexose-6-phosphate, D-glucosamine-6-phosphate, 2-deoxy-2-fluoro-2-D-manose-6-P, and any known derivatives, C-2 halogenated derivatives of hexose ring pyranoses, mannopyranoses, galactopyranoses, C-2-deoxy-2-fluoropyranoses, and any derivative, C-2 halogenated sugars derivatives, C-2 fluoro-, bromo-, chloro-, or iodo-sugars derivatives, fluoro, bromo, chloro, or iodo C-2 sugars derivatives, gluconolactones, glucuronic acid, glucopyranoside, and their phosphate derivatives, sugars modified at C-1 or C-5 by replacement of hydroxyl by fluorine or deoxygenation or replacement by a sulfur group, glucosyl fluoride, 1-deoxy-D-glucose, 5-thio-D-glucose, 3-deoxy or 3-fluoro-D-glucose or 4-deoxy or 4-fluoro-D-glucose, 2-fluoro- or 2-iodo-, or 2-thio-, or 2-methoxy- or 3-fluoro-, or 3,3 difluoro-, 3-iodo-, or 3-carboxylo-, or 3-thio-glyceraldehydes or glycerates, 3-fluoro-2-phosphoglycerate, phosphothioesters or other phosphor modified analogs, mannoheptulose mannoheptose, glucoheptose, N-acetylglucosamine, 6-aminonicotinamide acidosis-inducing agents, 2-deoxy-2-fluoro-D-glucose, citrate and halogenated derivatives of citrate, fructose 2,6-bisphosphate, bromoacetylethanolamine phosphate analogues, N-(2-methoxyethyl)-bromoacetamide, N-(2-ethoxyethyl)-bromoacetamide, N-(3-methoxypropyl)-bromoacetamide), iodoacetate, pentalenolactone, arsenic, 1,1-difluoro-3-phosphate-glycerol, oxamate, 2-fluoro-propionic acid or it salts, 2,2-difluoro-propionic acid, pyruvate modified at C-3 such as 3-halo-pyruvate, 3-halopropionic acid, and 2-thiomethylacetic acid, a stereoisomer, tautomer, racemate, prodrug, metabolite thereof, or a pharmaceutically acceptable salt, base, ester or solvate thereof.

30. A medical stent, a kit or a use according to any of claims 1 to 29 wherein said inhibitor of the TCA cycle inhibits at least one enzyme from the group consisting of pyruvate dehydrogenase, citrate synthase, aconitase, isocitrate lyase, alpha-ketoglutarate dehydrogenase complex, succinyl CoA synthetase, succinate dehydrogenase, fumarase, malate synthase, glutaminase, glutamate dehydrogenase, pyruvate dehydrogenase complex and malate dehydrogenase.

31. A medical stent, a kit or a use according to claim 30, wherein said inhibitor of the TCA cycle is any of halo-pyruvate, 3-fluoropyruvate, 3-chloropyruvate, 3-bromopyruvate, 3-iodopyruvate, arsenite, hypoglycin A, methylenecyclopropylacetic acid, alloxan, PNU, p-benzoquinone, fluoroacetate, fluoroacetyl-CoA, halogenated acetyl-CoA, fluoroacetamide, fluorocrotonate, ketone bodies, acetoacetate, hydroxybutyrate, acetone, halogenated ketone bodies, chloroacetoacetate, fluoroacetoacetate, bromoacetoacetate, fluorohydroxybutyrate, chlorohydroxybutyrate, bromohydroxybutyrate, fluoroacetone, chloroacetone, bromoacetone, halogenated acetic acid chloracetic acid, halogenated oleate, fluorocitrate, fluorocitrate 2R, 3R, halogenated citrate, bromocitrate, chlorocitrate, iodocitrate, dichlorovinyl-cysteine, halogenated aminoacids, malonate, pentachlorobutadienyl-cysteine, 2-bromohydroquinone, 3-nitropropionic acid, cis-crotonalide fungicides, 6-diazo-5-oxo-L-norleucine, glu-hydroxyoxamate, p-chloromercuriphenylsulphonic acid, L-glutamate gamma-hydroxamate, p-chloromercuriphenylsulphonic acid, alpha-amino-3-chloro-4,5-dihydro-5-isoxazoleacetic acid, halogenated glutamine, glutamate, a stereoisomer, tautomer, racemate, prodrug, metabolite thereof, or a pharmaceutically acceptable salt, base, ester or solvate thereof,

compounds of the general formula:

X—

CH₂—

CO—

COOH

wherein X represents a halide, a sulphonate, a carboxylate, an alkoxide, or an amine oxide,

compounds of the general formula;

wherein;

X represents a halide, a sulphonate, a carboxylate, an alkoxide, or an amine oxide,

R₁ may be OR, H, N(R″

)2, C1-C6 alkyl, C6-C12 aryl, C1-C6 heteroalkyl, or a C6-C12 heteroaryl.

independently, R″

may represent H, C1-C6 alkyl, or C6-C12 aryl,

independently, R may be H, alkali metal, C1-C6 alkyl, C6-C12 aryl or C(O)R′

,

R′

may represent H, C1-C20 alkyl or C6-C12 aryl,

compounds of the general formula (I);

where X is a halide, a sulfonate, a carboxylate, an alkoxide, an amine oxide or a OH, or

compounds of the general formula (II);

where X may be halide, a sulfonate, a carboxylate, an alkoxide, or an amine oxide, a OH.

32. A medical stent, a kit or a use according to any of claims 1 to 31, wherein said inhibitor of oxidative phosphorylation inhibits at least one of the respiratory complexes I, II, III, IV, and V.

33. A medical stent, a kit or a use according to any of claims 1 to 32, wherein said inhibitor of oxidative phosphorylation is any of rotenone, amytal, 1-methyl-4-phenylpyridinium, paraquat, myxothiazol, antimycin A, ubisemiquinone, cytochrome C, 4,6-diaminotriazine derivatives, cyanide, hydrogen sulfide, azide, formate, phosphine, carbon monoxide, 4′

-demethyl-epipodophyllotoxin thenylidene glucoside, tritylthioalanine, carminomycin, piperazinedione, dinitrophenol, dinitrocresol, 2-hydroxy-3-alkyl-1,4-naphtoquinones, apoptolidin aglycone, oligomycin, ossamycin, cytovaricin, naphtoquinone derivatives, dichloroallyl-lawsone, lapachol, rhodamine, rhodamine 6G, rhodamine 123, carbonyl cyanide p-trifluoromethoxyphenylhydrazone, valinomycin, cyhexatin, dichlorodiphenyltrichloroethane, chlordecone, arsenate, pentachlorophenol, benzonitrile, thiadiazole herbicides, salicylate, cationic amphilic drugs, amiodarone, perhexiline, gramicidin, calcimycin, pentachlorobutadienyl-cysteine, trifluorocarbonylcyanide phenylhydrazone, atractyloside, lysophospholipids, n-ethylmaleimide, mersanyl, or p-benzoquinone, a stereoisomer, tautomer, racemate, prodrug, metabolite thereof, or a pharmaceutically acceptable salt, base, ester or solvate thereof.

36. A medical stent, a kit or a use according to any of claims 1 to 35, wherein said composition further comprises one or more polymers to facilitate attachment of the composition to the stent and/or slow release of the composition.

37. A medical stent, use, or kit according to claim 36, wherein said polymer is one or more of:

aliphatic polyesters, poly(amino acids), copoly(ether-esters), polyalkylenes oxalates, polyamides, poly(iminocarbonates), polyanhydrides, polyorthoesters, polyoxaesters, polyamidoesters, polylactic acid, polyethylene oxide, polycaprolactone, polyhydroxybutyrate valerates, polyoxaesters containing amido groups, poly(anhydrides), polyphosphazenes, silicones, biomolecules and blends thereof,

lactic acid D-,L- and meso lactide, epsilon-caprolactone, glycolide glycolic acid, hydroxybutyrate, hydroxyvalerate, para-dioxanone, trimethylene carbonate and its alkyl derivatives, 1,4-dioxepan-2-one, 1,5-dioxepan-2-one, 6,6-dimethyl-1,4-dioxan-2-one and polymer blends thereof,

polyanhydrides from diacids of the form HOOC—

C₆H₄—

O—

(CH₂)m-O—

C₆H₄—

COOH wherein m is an integer in the range of from 2 to 8 and copolymers thereof with aliphatic alpha-omega diacids of up to 12 carbons,

naturally enzymatically or are hydrolytically unstable polymers, fibrin, fibrinogen, collagen, gelatin, glycosaminoglycans, elastin, and absorbable biocompatible polysaccharides such as chitosan, starch, fatty acids and esters thereof, glucoso-glycans and hyaluronic acid,

hydrogels

polyurethanes, silicones, poly(meth)acrylates, polyesters, polyalkyl oxides, polyethylene oxide, polyvinyl alcohols, polyethylene glycols and polyvinyl pyrrolidone, as well as, hydrogels, hydrogels from crosslinked polyvinyl pyrrolidinone and polyesters, polyolefins, polyisobutylene and ethylene-alphaolefin copolymers, acrylic polymers, methacrylate and copolymers, vinyl halide polymers and copolymers, polyvinyl chloride, polyvinyl ethers, polyvinyl methyl ether, polyvinylidene polyvinylidene fluoride polyvinylidene chloride, polyacrylonitrile, polyvinyl ketones, polyvinyl aromatics, polystyrene, polyvinyl esters, polyvinyl acetate, copolymers of vinyl monomers with each other and olefins, etheylene-methyl methacrylate copolymers, acrylonitrile-styrene copolymers, ABS resins and ethylene-vinyl acetate copolymers, polyamides, Nylon 66 and polycaprolactam, alkyd resins, polycarbonates, polyoxymethylenes, polyimides, polyethers, epoxy resins, polyurethanes, rayon, rayon-triacetate, cellulose, cellulose acetate, cellulose acetate butyrate, cellophane, cellulose nitrate, cellulose propionate, cellulose ethers, carboxymethyl cellulose and hydoxyalkyl celluloses, and combinations thereof,

polyamides of the form —

NH—

(CH₂)n-CO— and

NH—

(CH₂)x-NH—

CO—

(CH₂)y-CO, wherein n is preferably an integer in from 6 to 13;

x is an integer in the range of form 6 to 12; and

y is an integer in the range of from 4 to 16,

bioabsorbable elastomers, aliphatic polyester elastomers,

elastomeric copolymers of epsilon-caprolactone and glycolide, preferably having a mole ratio of epsilon-caprolactone to glycolide of from about 35;

65 to about 65;

35, more preferably 45;

55 to 35;

65,

elastomeric copolymers of epsilon-caprolactone and lactide, L-lactide, D-lactide blends thereof or lactic acid copolymers, preferably having a mole ratio of epsilon-caprolactone to lactide of from about 35;

65 to about 90;

10 and more preferably from about 35;

65 to about 65;

35 and most preferably from about 45;

55 to 30;

70 or from about 90;

10 to about 80;

20,

elastomeric copolymers of p-dioxanone and lactide including L-lactide, D-lactide and lactic acid, preferably having a mole ratio of p-dioxanone to lactide of from about 40;

60 to about 60;

40,

elastomeric copolymers of epsilon-caprolactone and p-dioxanone, preferably having a mole ratio of epsilon-caprolactone to p-dioxanone of from about 30;

70 to about 70;

30,

elastomeric copolymers of p-dioxanone and trimethylene carbonate, preferably having a mole ratio of p-dioxanone to trimethylene carbonate of from about 30;

70 to about 70;

30,

elastomeric copolymers of trimethylene carbonate and glycolide, preferably having a mole ratio of trimethylene carbonate to glycolide of from about 30;

70 to about 70;

30,

elastomeric copolymer of trimethylene carbonate and lactide including L-lactide, D-lactide, blends thereof or lactic acid copolymers, preferably having a mole ratio of trimethylene carbonate to lactide of from about 30;

70 to about 70;

30 and blends thereof.

38. A medical stent, a kit or a use according to any of claims 1 to 37 wherein:

the glycolysis inhibitor is present in a quantity to primarily inhibit the glycolytic pathway, and

the TCA cycle inhibitor, is present in a quantity to secondarily inhibit the TCA cycle.

39. A medical stent, a kit or a use according to any of claims 1 to 37 wherein:

the PPP inhibitor is present in a quantity to primarily inhibit the PPP pathway, and

the TCA cycle or oxidative phosphorylation inhibitor or both, is present in a quantity to secondarily inhibit the TCA cycle and/or oxidative phosphorylation pathways respectively.

40. A medical stent or kit according to any of claims 1 to 8, 14 to 39 suitable for use in inhibiting cell proliferation.

41. A use of a medical stent or kit according to any of claims 1 to 8, 14 to 39 for the preparation of a medical device for inhibiting cell proliferation.

44. A medical stent, kit or use according to any of claims 1 to 43 wherein the stent is placed in an artery or vein.

45. A medical stent, kit or use according to any of claims 1 to 43 wherein the stent is placed in a bronchial duct.

46. A medical stent, kit or use according to any of claims 1 to 43, wherein the stent is placed in a digestive duct such as esophagus, bowel, and/or biliary tract.

47. A medical stent, kit or use according to any of claims 1 to 43, wherein the stent is placed in a gynecological duct such as uterus, cervix, and/or vagina.

48. A medical stent, kit or use according to any of claims 1 to 43, wherein the stent is placed in a resection cavity or scar.

63. A use or kit according to any of claim 62, wherein said slow release agent is any as defined in claim 18.

65. A use or kit according to claim 64 wherein a nano-capsule is a nanocapsule as defined in claim 20.

66. A use or kit according to claim 64 wherein a micro-capsule is a micro-capsule as defined in claim 21.

68. A use or kit according claim 67, wherein said solubilising agent is a solubilizing agent as defined in any of claims 23 to 26.

80. A use or kit according to any of claims 52 to 79 wherein said inhibitor of glycolysis is as defined in any of claims 27 to 29.

81. A use or kit according to any of claims 52 to 80 wherein said inhibitor of the TCA cycle is as defined in claims 30 or 31.

9. Use of a composition comprising at least one type of inhibitor of glycolysis and/or TCA cycle, for the preparation of a composition for providing a medical stent for inhibiting cell proliferation.

10. Use of a composition comprising at least one type of inhibitor of glycolysis and/or TCA cycle, for the preparation of a composition for providing a medical stent for sensitizing proliferating cells to treatment by radiotherapy.

12. Use according to any of claims 9 to 11, wherein said composition further comprises at least one inhibitor of the PPP.

13. Use according to any of claims 9 to 12, wherein said composition further comprises at least one inhibitor of the oxidative phosphorylation.

34. A medical stent, a kit or a use according to any of claims 2 to 33, wherein said inhibitor of the PPP inhibits at least one enzyme from the group consisting of glucose-6-phosphate dehydrogenase, lactonase, 6-phosphogluconate dehydrogenase, phosphopentose isomerase, phosphopentose epimerase, transketolase, and transaldolase.

35. A medical stent, a kit or a use according to any of claims 2 to 34, wherein said inhibitor of the PPP is any of 6-aminonicotinamide and 2-Amino-2-deoxy-D-glucose-6-phophate, a stereoisomer, tautomer, racemate, prodrug, metabolite thereof, or a pharmaceutically acceptable salt, base, ester or solvate thereof.

42. A medical stent, kit or use according to any of claims 9 to 41, wherein said cell proliferation is restenosis or stenosis.

43. A medical stent, kit or use according to any of claims 9 to 41, wherein said cell proliferation is cancer.

82. A use or kit according to any of claims 53 to 81, wherein said inhibitor of the PPP is as defined in claims 34 or 35.

83. A use or kit according to any of claims 9 to 82 wherein the oxidative phosphorylation inhibitor is present in a quantity to oxidative phosphorylation pathway.

11. Use of a composition comprising at least one type of inhibitor of glycolysis and/or TCA cycle, for the preparation of a composition for providing a medical stent for sensitizing proliferating cells to treatment by chemotherapy.

14. A kit comprising a) at least one medical stent and b) a composition comprising at least one type of inhibitor of glycolysis and/or TCA cycle.

15. A kit according to claim 14, wherein said composition further comprises at least one inhibitor of the PPP.

16. A kit according to claim 14, wherein said composition further comprises at least one inhibitor of the oxidative phosphorylation.

86. A use or kit according to claim 85, wherein said polymer is as defined in claim 15.

49. Use of a composition comprising at least one inhibitor of oxidative phosphorylation, for the preparation of a composition for providing a medical stent for inhibiting cell profileration via inhibition of the oxidative phosphorylation pathway.

52. Use according to any of claims 49 to 51, wherein said composition further comprises at least one inhibitor of glycolysis and/or the TCA cycle.

53. Use according to any of claims 49 to 52, wherein said composition further comprises at least one inhibitor of the pentose phosphate pathway, PPP.

54. Use according to any of claims 49 to 53, wherein said stent is provided with one or more cavities for containing and releasing said composition.

55. Use according to any of claims 49 to 54, wherein said stent is at least partly made from a material which is biodegradable in situ.

56. Use according to any of claims 49 to 55, wherein said stent comprises a magnesium based alloy.

57. Use according to any of claims 49 to 56, wherein said stent is at least partly made from a material which is non-biodegradable in situ and is impregnated with said composition.

58. Use according to any of claims 49 to 57, wherein said stent is at least partly provided with said composition.

62. A use or kit according to any of claims 49 to 58, or a kit according to any of claims 59 to 61, wherein said composition further comprises one or more slow release agents to facilitate slow release of inhibitor.

64. A use or kit according to any of claims 49 to 63, wherein at least one inhibitor is encapsulated in a micro-capsule or nano-capsule.

67. A use or kit according to any of claims 49 to 66, wherein at least one of said inhibitors is coupled to solubilising agent.

69. A use or kit according to any of claim 49 to 68 wherein said inhibitor of glycolysis inhibits at least one enzyme from the group consisting of hexokinase, glucokinase, phosphoglucose isomerase, phosphofructokinase, aldolase, triose phosphate isomerase, glyceraldehyde 3-phosphate dehydrogenase, phosphoglycerate kinase, phosphoglyceromutase, enolase, pyruvate kinase, and lactate dehydrogenase.

70. A use or kit according to any of claims 49 to 69, wherein said inhibitor of oxidative phosphorylation is an inhibitor of enzyme complex I.

71. A use or kit according to claim 70, wherein said inhibitor of complex I is any of tritylthioalanine, carminomycin, and piperazinedione, rotenone, amytal, 1-methyl-4-phenylpyridinium, paraquat, methylene blue, and ferricyanide.

72. A use or kit according to any of claims 49 to 69, wherein said inhibitor of oxidative phosphorylation is an inhibitor of enzyme complex II.

73. A use or kit according to any of claims 49 to 69, wherein said inhibitor of oxidative phosphorylation is an inhibitor of complex II.

74. A use or kit according to claim 73, wherein said inhibitor of complex III is any of myxothiazol, antimycin A, ubisemiquinone, cytochrome C, 4,6-diaminotriazine derivatives, metothrexate or electron acceptors such as phenazine methosulfate and 2,6-Dichlorophenol-indophenol.

75. A use or kit according to any of claims 49 to 69, wherein said inhibitor of oxidative phosphorylation is an inhibitor of enzyme complex IV

76. A use or kit according to claim 75, wherein said inhibitor of enzyme complex IV is any of cyanide, hydrogen sulfide, azide, formate, phosphine, carbon monoxide and electon acceptor ferricyanide.

77. A use or kit according to any of claims 49 to 69, wherein said inhibitor of oxidative phosphorylation is an inhibitor of enzyme complex V

78. A use or kit according to claim 77, wherein said inhibitor of enzyme complex V is any of 4′

-demethyl-epipodophyllotoxin thenylidene glucoside, tritylthioalanine, carminomycin, piperazinedione, dinitrophenol, dinitrocresol, 2-hydroxy-3-alkyl-1,4-naphtoquinones, apoptolidin aglycone, oligomycin, ossamycin, cytovaricin, naphtoquinone derivatives (e.g. dichloroallyl-lawsone and lapachol), rhodamine, rhodamine 123, rhodamine 6G, arbonyl cyanide p-trifluoromethoxyphenylhydrazone, valinomycin, rothenone, safranine O, cyhexatin, dichlorodiphenyltrichloroethane, chlordecone, arsenate, pentachlorophenol, benzonitrile, thiadiazole herbicides, salicylate, cationic amphilic drugs (amiodarone, perhexiline), gramicidin, calcimycin, pentachlorobutadienyl-cysteine, trifluorocarbonylcyanide phenylhydrazone.

79. A use or kit according to any of claims 49 to 69, wherein said inhibitor of oxidative phosphorylation is any of atractyloside, lysophospholipids, n-ethylmaleimide, mersanyl, and p-benzoquinone.

84. A use or kit according to any of claims 49 to 83 wherein said stent is provided with an amount of composition to deliver a concentration between 10 and 60 mg oxidative phosphorylation inhibitor/kg.

85. A use or kit according to any of claims 49 to 84 wherein said composition further comprises one or more polymers to facilitate attachment of the composition to the stent and/or slow release of the composition.

88. A use of a kit according to any of claims 57 to 85 for the preparation of a medical device for inhibiting cell proliferation.

89. A use or kit according to any of claims 49 to 88, wherein said cell proliferation is restenosis or stenosis.

90. A use or kit according to any of claims 49 to 89, wherein said cell proliferation is cancer.

91. A use or kit according to any of claims 49 to 90 wherein the stent is placed in an artery or vein.

92. A use or kit according to any of claims 49 to 90 wherein the stent is placed in a bronchial duct.

93. A use or kit according to any of claims 49 to 90, wherein the stent is placed in a digestive duct such as esophagus, bowel, and/or biliary tract.

94. A use or kit according to any of claims 49 to 90, wherein the stent is placed in a gynecological duct such as uterus, cervix, and/or vagina.

95. A use or kit according to any of claims 49 to 90, wherein the stent is placed in a resection cavity or scar.

50. Use of a composition comprising at least one inhibitor of oxidative phosphorylation, for the preparation of a composition for providing a medical stent for sensitizing proliferating cells to treatment by radiotherapy.

51. Use of a composition comprising at least one inhibitor of oxidative phosphorylation, for the preparation of a composition for providing a medical stent for sensitizing proliferating cells to treatment by chemotherapy.

59. A kit comprising a) at least one medical stent and b) a composition comprising at least one type of inhibitor of oxidative phosphorylation.

60. A kit according to claim 59, wherein said composition further comprises at least one inhibitor of the PPP.

61. A kit according to claims 59 or 60, wherein said composition further comprises at least one inhibitor of the glycolysis and/or TCA cycle.

87. A kit according to any of claims 59 to 82 suitable for use in inhibiting cell proliferation.

96. A medical stent at least partly covered with an expandable membrane over the expandable region, said membrane provided with a composition comprising at least one type of inhibitor of glycolysis and/or the TCA cycle and/or oxidative phosphorylation.

97. A medical stent according to claim 96 wherein said membrane is biodegradable or non biodegradable material.

98. A medical stent according to claims 96 or 97 wherein said membrane is at least partly formed from any of aliphatic polyester copolymers, elastomeric copolymers of epsilon-caprolactone and glycolide, elastomeric copolymers of E-caprolactone and lactide, copolymers of E-caprolactone and lactic acid, elastomeric copolymers of p-dioxanone and lactide, elastomeric copolymers of p-dioxanone and lactic acid, elastomeric copolymers of epsilon-caprolactone and p-dioxanone, elastomeric copolymers of p-dioxanone and trimethylene carbonate, elastomeric copolymers of trimethylene carbonate and glycolide, elastomeric copolymer of trimethylene carbonate and lactide, or elastomeric copolymer of trimethylene carbonate and lactic acid.

99. A medical stent according to any of claims 96 to 98, further comprising at least one inhibitor of the pentose phosphate pathway, PPP.

100. A medical stent according to any of claims 96 to 99, wherein said stent is at least partly made from a material which is biodegradable in situ and is impregnated with said composition.

101. A medical stent according to any of claims 96 to 100, wherein said stent comprises a magnesium based alloy.

102. A medical stent according to any of claims 96 to 99, wherein said stent is at least partly made from a material which is non-biodegradable.

103. A medical stent according to any of claims 96 to 102, wherein said membrane is at least partly provided with said composition.

110. A medical stent, use or kit according to any of claims 96 to 109, wherein said composition further comprises one or more slow release agents to facilitate slow release of inhibitor.

111. A medical stent, use or kit according to any claim 110, wherein said slow release agent is any as defined in claim 18.

112. A medical stent, use or kit according to any of claims 96 to 111, wherein at least one type of inhibitor of glycolysis and/or the TCA cycle,and/or oxphos is encapsulated a micro-capsule or nano-capsule.

113. A medical stent, use or kit according to claim 112 wherein a nano-capsule is a nano-capsule as defined in claim 20.

114. A medical stent according to claim 112 wherein a micro-capsule is a micro-capsule as defined in claim 21

115. A medical stent, use or kit according to any of claims 96 to 114, wherein at least one of said inhibitors is coupled to solubilising agent.

116. A medical stent, use or kit according to claim 115, wherein said solubilising agent is a solubilizing agent as defined in any of claims 23 to 26.

117. A medical stent, use or kit according to any of claims 96 to 116 wherein said inhibitor of glycolysis is an inhibitor as defined in any of claims 27 to 29.

118. A medical stent, a kit or a use according to any of claims 96 to 117 wherein said inhibitor of the TCA cycle is an inhibitor as defined in claims 30 or 31.

119. A medical stent, a kit or a use according to any of claims 96 to 117, wherein said inhibitor of oxidative phosphorylation is an inhibitor as defined in claims 32 or 33.

120. A medical stent, use or kit according to any of claims 96 to 119, wherein said composition further comprises one or more polymers to facilitate attachment of the composition to the membrane and/or slow release of the composition.

121. A medical stent, use or kit according to claim 120, wherein said polymer is one or more of the polymers as defined in claim 37.

122. A medical stent, a kit or a use according to any of claims 96 to 121, suitable for use in inhibiting cell proliferation.

125. A medical stent, a kit or a use according to any of claims 96 to 124 wherein said stent is placed in an artery or vein.

126. A medical stent, a kit or a use according to any of claims 96 to 124 wherein said stent is placed in a bronchial duct.

127. A medical stent, a kit or a use according to any of claims 96 to 124, wherein said stent is placed in a digestive duct such as esophagus, bowel, and/or biliary tract.

128. A medical stent, a kit or a use according to any of claims 96 to 124, wherein said stent is placed in a gynecological duct such as uterus, cervix, and/or vagina.

129. A medical stent, a kit or a use according to any of claims 96 to 124, wherein said stent is placed in a malignant or benign resection cavity or scar.

104. Use of a composition comprising at least one type of inhibitor of glycolysis and/or TCA cycle and/or oxidative phsophorylation, for the preparation of a composition for providing a medical stent at least partly covered with an expandable membrane for inhibiting cell proliferation.

107. Use according to any of claim 104 to 106, wherein said composition further comprises at least one inhibitor of the PPP.

123. A medical stent, a kit or a use according to any of claims 104 to 106, 110 to 122, wherein said cell proliferation is restenosis or stenosis.

124. A medical stent, a kit or a use according to any of claims 104 to 106, 110 to 122, wherein said cell proliferation is cancer.

105. Use of a composition comprising at least one type of inhibitor of glycolysis and/or TCA cycle and/or oxidative phsophorylation, for the preparation of a composition for providing a medical stent at least partly covered with an expandable membrane for sensitizing proliferating cells to radiotherapy.

106. Use of a composition comprising at least one type of inhibitor of glycolysis and/or TCA cycle and/or oxidative phsophorylation, for the preparation of a composition for providing a medical stent at least partly covered with an expandable membrane for sensitizing a proliferating cells to chemotherapy.

108. A kit comprising a) at least one medical stent at least partly covered with an expandable membrane and b) a composition comprising at least one type of inhibitor of glycolysis and/or TCA cycle and/or oxidative phosphorylation.

109. A kit according to claim 108, wherein said composition further comprises at least one inhibitor of the PPP.