System and method for the local delivery of drugs

Abstract

A method of treating a specific site in a mammal with a drug comprises (a) providing a carrier material which reflects or absorbs or emits electromagnetic or mechanical vibrations enabling the monitoring of the carrier material, (b) providing a drug associated with the carrier material, (c) providing a targeting agent associated with the carrier material, the targeting agent being capable of binding to the specific site in the mammal, (d) delivering the carrier material and the drug to the specific site in the mammal, and (e) monitoring the mammal to detect arrival of the carrier material at the specific site. A local and site-specific drug delivery system for delivering a drug to a specific site within an individual comprises a carrier material which reflects or absorbs or emits electromagnetic or mechanical vibrations enabling the monitoring of the carrier material, a drug associated with the carrier material, and a targeting agent associated with the carrier material that delivers the carrier material and the drug to a specific site within the individual, the targeting agent being capable of binding to the specific site within the individual.

1 . A method of treating a specific site in a mammal with a drug, said method comprising: 
 (a) providing a carrier material which reflects or absorbs or emits electromagnetic or mechanical vibrations enabling the monitoring of said carrier material;    (b) providing a drug associated with said carrier material, said drug being selected from the group consisting of acebutolol, acetylsalicylic acid, adenosine, ATP, alfentanil, alprazolam, azlocillin, betamethasone, bleomycin, captopril, carbenicillin, cefamandole, cefazolin, cefonicid, ceforanide, cefotaxime, cefoxitin, clonidine, cloxacillin, cyclophosphamide, cytarabine, dexamethasone, dicloxacillin, diazepam, diazoxide, digitoxin, digoxin, diltiazem, diphenihydramine, disopyramide, doxorubicin, doxycycline, ceftazidime, ceftizoxime, cefuroxime, cephalexin, cephalothin, cephapirin, chloramphenicol, chloroquine, chlorothiazide, chlorpropormide, chlorthalidone, cimetidine, clofibrate, ibuprofen, imipramine, indomethacin, isosorbide dinitrate, ketoprofen, labetalol, lidocaine, lorazepam, lorcainide, meperidine, mercaptopurine, methadone, methicillin, erythromycin, ethambutol, fentanyl, flucytosine, flunitrazepam, fluorouracil, flurazepam, furosemide, gold sodium thiomalate, haloperidol, heparin, hexobarbital, hydrochlorothiazide, nortriptyline, oxacillin, oxazepam, phenobarbital, phenylbutazone, phenytoin, pindolol, prazosin, prednisolone, prednisone, protenecid, procainamide, propranolol, methothexate, methyldopa, methylprednisolone, metoprolol, metronidazole, mexiletine, mezlocillin, minocycline, morphine, moxalactam, nadolol, nafcillin, naproxen, nifedipine, nitrazepam, theopental, ticarcillin, timolol, tocainide, tolbutamide, tolmetin, triamterene, triazolam, trimethoprim, tubocurarine, valproic acid, verapamil, warfarin, protriptyline, pyrimethamine, quinidine, ranitidine, rifampin, salicylic acid, streptomycin, streptokinase, sulfadiazine, sulfamethoxazole, sulfisoxazole, ternazepam, terbutaline, tetracycline, theophylline, and tissue plasminogen activator (tpa);    (c) providing a targeting agent associated with said carrier material, said targeting agent being capable of binding to said specific site in the mammal;    (d) delivering said carrier material and said drug to said specific site in the mammal; and    (e) monitoring the mammal to detect arrival of said carrier material at said specific site.    
     
     
         2 . A drug delivery system as defined in  claim 1  wherein said targeting agent is a protein.  
     
     
         3 . A drug delivery system as defined in  claim 1  wherein said targeting agent is an antibody.  
     
     
         4 . A drug delivery system as defined in  claim 1  wherein said targeting agent is a glycogen IIa/IIB receptor antibody, Von Willebrand's factor antibody, an antitumor antibody, hepatic cellular antibody, a white blood cell antibody, or antifibrin.  
     
     
         5 . A method as defined in  claim 1  comprising generating an image of said carrier material at said specific site.  
     
     
         6 . A method as defined in  claim 1  additionally comprising (f) inducing said drug to be released from said carrier material when said carrier material and said drug are at said specific site.  
     
     
         7 . A method as defined in  claim 1  additionally comprising (f) inducing said drug to be released from said carrier material when said carrier material and said drug are at said specific site by subjecting said carrier material to ultrasonic vibrations.  
     
     
         8 . A method of treating a specific site in a mammal with a drug, said method comprising: 
 (a) providing a carrier material which reflects or absorbs or emits electromagnetic or mechanical vibrations enabling the monitoring of said carrier material;    (b) providing a drug associated with said carrier material;    (c) providing a targeting agent associated with said carrier material, said targeting agent being capable of binding to said specific site in the mammal;    (d) delivering said carrier material and said drug to said specific site in the mammal; and    (e) monitoring the mammal to detect arrival of said carrier material at said specific site.    
     
     
         9 . A method as defined in  claim 8  wherein said drug is selected from the group consisting of acebutolol, acetylsalicylic acid, adenosine, ATP, alfentanil, alprazolam, azlocillin, betamethasone, bleomycin, captopril, carbenicillin, cefamandole, cefazolin, cefonicid, ceforanide, cefotaxime, cefoxitin, clonidine, cloxacillin, cyclophosphamide, cytarabine, dexamethasone, dicloxacillin, diazepam, diazoxide, digitoxin, digoxin, diltiazem, diphenihydramine, disopyramide, doxorubicin, doxycycline, ceftazidime, ceftizoxime, cefuroxime, cephalexin, cephalothin, cephapirin, chloramphenicol, chloroquine, chlorothiazide, chlorpropormide, chlorthalidone, cimetidine, clofibrate, ibuprofen, imipramine, indomethacin, isosorbide dinitrate, ketoprofen, labetalol, lidocaine, lorazepam, lorcainide, meperidine, mercaptopurine, methadone, methicillin, erythromycin, ethambutol, fentanyl, flucytosine, flunitrazepam, fluorouracil, flurazepam, furosemide, gold sodium thiomalate, haloperidol, heparin, hexobarbital, hydrochlorothiazide, nortriptyline, oxacillin, oxazepam, phenobarbital, phenylbutazone, phenytoin, pindolol, prazosin, prednisolone, prednisone, protenecid, procainamide, propranolol, methothexate, methyldopa, methylprednisolone, metoprolol, metronidazole, mexiletine, mezlocillin, minocycline, morphine, moxalactam, nadolol, nafcillin, naproxen, nifedipine, nitrazepam, theopental, ticarcillin, timolol, tocainide, tolbutamide, tolmetin, triamterene, triazolam, trimethoprim, tubocurarine, valproic acid, verapamil, warfarin, protriptyline, pyrimethamine, quinidine, ranitidine, rifampin, salicylic acid, streptomycin, streptokinase, sulfadiazine, sulfamethoxazole, sulfisoxazole, ternazepam, terbutaline, tetracycline, theophylline, and tissue plasminogen activator (tpa).  
     
     
         10 . A method as defined in  claim 8  wherein said drug comprises a chemotherapy agent, a thrombolytic drug, or an anti-infection agent.  
     
     
         11 . A method as defined in  claim 8  wherein said targeting agent is a protein.  
     
     
         12 . A method as defined in  claim 8  wherein said targeting agent is an antibody.  
     
     
         13 . A method as defined in  claim 8  wherein said targeting agent is a glycogen IIa/IIB receptor antibody, Von Willebrand's factor antibody, an antitumor antibody, hepatic cellular antibody, a white blood cell antibody, or antifibrin.  
     
     
         14 . A method as defined in  claim 8  comprising generating an image of said carrier material at said specific site.  
     
     
         15 . A method as defined in  claim 8  additionally comprising (f) inducing said drug to be released from said carrier material when said carrier material and said drug are at said specific site.  
     
     
         16 . A method as defined in  claim 8  additionally comprising (f) inducing said drug to be released from said carrier material when said carrier material and said drug are at said specific site by subjecting said carrier material to ultrasonic vibrations.  
     
     
         17 . A method of delivering a drug to a specific target site in an individual, said method comprising: 
 (a) administering an ultrasonic contrast agent-drug complex to a specific target site in an individual, said complex comprising an ultrasonic contrast agent, a drug, and a targeting agent capable of binding said ultrasonic contrast agent to said specific target site in the individual;    (b) monitoring the individual using ultrasound to determine arrival of said complex at said specific target site in the individual; and    (c) releasing said drug at said specific target site by applying sufficient energy to rupture said complex at said specific target site.    
     
     
         18 . A method as defined in  claim 17  wherein said drug is selected from the group consisting of acebutolol, acetylsalicylic acid, adenosine, ATP, alfentanil, alprazolam, azlocillin, betamethasone, bleomycin, captopril, carbenicillin, cefamandole, cefazolin, cefonicid, ceforanide, cefotaxime, cefoxitin, clonidine, cloxacillin, cyclophosphamide, cytarabine, dexamethasone, dicloxacillin, diazepam, diazoxide, digitoxin, digoxin, diltiazem, diphenihydramine, disopyramide, doxorubicin, doxycycline, ceftazidime, ceftizoxime, cefuroxime, cephalexin, cephalothin, cephapirin, chloramphenicol, chloroquine, chlorothiazide, chlorpropormide, chlorthalidone, cimetidine, clofibrate, ibuprofen, imipramine, indomethacin, isosorbide dinitrate, ketoprofen, labetalol, lidocaine, lorazepam, lorcainide, meperidine, mercaptopurine, methadone, methicillin, erythromycin, ethambutol, fentanyl, flucytosine, flunitrazepam, fluorouracil, flurazepam, furosemide, gold sodium thiomalate, haloperidol, heparin, hexobarbital, hydrochlorothiazide, nortriptyline, oxacillin, oxazepam, phenobarbital, phenylbutazone, phenytoin, pindolol, prazosin, prednisolone, prednisone, protenecid, procainamide, propranolol, methothexate, methyldopa, methylprednisolone, metoprolol, metronidazole, mexiletine, mezlocillin, minocycline, morphine, moxalactam, nadolol, nafcillin, naproxen, nifedipine, nitrazepam, theopental, ticarcillin, timolol, tocainide, tolbutamide, tolmetin, triamterene, triazolam, trimethoprim, tubocurarine, valproic acid, verapamil, warfarin, protriptyline, pyrimethamine, quinidine, ranitidine, rifampin, salicylic acid, streptomycin, streptokinase, sulfadiazine, sulfamethoxazole, sulfisoxazole, ternazepam, terbutaline, tetracycline, theophylline, and tissue plasminogen activator (tpa).  
     
     
         19 . A method as defined in  claim 17  wherein said drug comprises a chemotherapy agent, a thrombolytic drug, or an anti-infection agent.  
     
     
         20 . A method as defined in  claim 17  wherein said targeting agent is a protein.  
     
     
         21 . A method as defined in  claim 17  wherein said targeting agent is an antibody.  
     
     
         22 . A method as defined in  claim 17  wherein said targeting agent is a glycogen IIa/IIB receptor antibody, Von Willebrand's factor antibody, an antitumor antibody, hepatic cellular antibody, a white blood cell antibody, or antifibrin.  
     
     
         23 . A method as defined in  claim 17  comprising generating an image of said carrier material at said specific site.  
     
     
         24 . A method as defined in  claim 17  comprising subjecting said carrier material to ultrasonic vibrations.  
     
     
         25 . A method as defined in  claim 17  comprising imaging said target site using ultrasound energy.  
     
     
         26 . A local and site-specific drug delivery system for delivering a drug to a specific site within an individual, said drug delivery system comprising: 
 a carrier material which reflects or absorbs or emits electromagnetic or mechanical vibrations enabling the monitoring of said carrier material;    a drug associated with said carrier material; and    a targeting agent associated with said carrier material that delivers said carrier material and said drug to a specific site within the individual, said targeting agent being capable of binding to said specific site within the individual.    
     
     
         27 . A drug delivery system as defined in  claim 26  wherein said drug is selected from the group consisting of acebutolol, acetylsalicylic acid, adenosine, ATP, alfentanil, alprazolam, azlocillin, betamethasone, bleomycin, captopril, carbenicillin, cefamandole, cefazolin, cefonicid, ceforanide, cefotaxime, cefoxitin, clonidine, cloxacillin, cyclophosphamide, cytarabine, dexamethasone, dicloxacillin, diazepam, diazoxide, digitoxin, digoxin, diltiazem, diphenihydramnine, disopyramide, doxorubicin, doxycycline, ceftazidime, ceftizoxime, cefliroxime, cephalexin, cephalothin, cephapirin, chloramnphenicol, chloroquine, chlorothiazide, chlorpropormide, chlorthalidone, cimetidine, clofibrate, ibuprofen, imipramine, indomethacin, isosorbide dinitrate, ketoprofen, labetalol, lidocaine, lorazepam, lorcainide, meperidine, mercaptopurine, methadone, methicillin, erythromycin, ethambutol, fentanyl, flucytosine, flunitrazepam, fluorouracil, flurazepam, furosemide, gold sodium thiomalate, haloperidol, heparin, hexobarbital, hydrochlorothiazide, nortriptyline, oxacillin, oxazepam, phenobarbital, phenylbutazone, phenytoin, pindolol, prazosin, prednisolone, prednisone, protenecid, procainamide, propranolol, methothexate, methyldopa, methylprednisolone, metoprolol, metronidazole, mexiletine, mezlocillin, minocycline, morphine, moxalactam, nadolol, nafcillin, naproxen, nifedipine, nitrazepam, theopental, ticarcillin, timolol, tocainide, tolbutamide, tolmetin, triamterene, triazolam, trimethoprim, tubocurarine, valproic acid, verapamil, warfarin, protriptyline, pyrimethamine, quinidine, ranitidine, rifampin, salicylic acid, streptomycin, streptokinase, sulfadiazine, sulfamethoxazole, sulfisoxazole, ternazepam, terbutaline, tetracycline, theophylline, and tissue plasminogen activator (tpa).  
     
     
         28 . A drug delivery system as defined in  claim 26  wherein said drug comprises a chemotherapy agent, a thrombolytic drug, or an anti-infection agent.  
     
     
         29 . A drug delivery system as defined in  claim 26  wherein said targeting agent is a protein.  
     
     
         30 . A drug delivery system as defined in  claim 26  wherein said targeting agent is an antibody.  
     
     
         31 . A drug delivery system as defined in  claim 26  wherein said targeting agent is a glycogen IIa/IIB receptor antibody, Von Willebrand's factor antibody, an antitumor antibody, hepatic cellular antibody, a white blood cell antibody, or antifibrin.  
     
     
         32 . A drug delivery system as defined in  claim 26  additionally comprising an apparatus that monitors delivery of said drug to said specific site.  
     
     
         33 . A drug delivery system as defined in  claim 26  additionally comprising an apparatus that induces release of said drug from said carrier material when said carrier material is at said specific site.