Ultrasonic Dispersion of Compositions in Tissue

Abstract

Therapeutic agents, diagnostic agents and other compositions can be effectively delivered to target tissues using ultrasonic dispersion. For example, a therapeutic agent in solution may be injected subcutaneously in the vicinity of a target tissue in a patient. External ultrasound is used to disperse the therapeutic agent in the target tissue. The disclosed methods provide increased concentrations of therapeutic agents in tissue relative to traditional delivery methods, thereby improving therapeutic outcomes while reducing costs. In addition the methods can be used to deliver effective concentrations of therapeutic agents to tissues with limited blood supply.

1 .- 7 . (canceled) 
     
     
         8 . A method of treating a patient comprising:
 identifying a treatment field associated with the patient;   subcutaneously injecting a solution comprising a therapeutic dose of a drug dissolved therein to the treatment field and in a vicinity of a target tissue; and   applying ultrasound transcutaneously toward the treatment field associated with the target tissue and the subcutaneously injected solution, wherein the transcutaneously applied ultrasound is applied for 5 minutes or less at a power density of 2.5 to 4 W/cm2 and at a frequency less than 5 MHz such that the ultrasound interacts with the subcutaneously injected solution to disperse the solution with the therapeutic dose of drug dissolved therein through the treatment field and into the target tissue via microstreaming or by cavitation, the therapeutic dose of drug dissolved in the solution being dispersed through the target tissue at a concentration of at least 200 micrograms/ml fifty minutes after the application of transcutaneous ultrasound, wherein the concentration of drug in the target tissue is therapeutically effective against a pathogen in the target tissue while maintaining serum concentration of the drug to less than 10 micrograms/ml one hour after the application of transcutaneous ultrasound; and   monitoring a temperature during application of the transcutaneous ultrasound with a temperature monitor to identify a need to cease the broadcast of ultrasound toward the treatment field when a monitored temperature exceeds a temperature threshold.   
     
     
         9 . The treatment method of  claim 8 , further comprising:
 prewarming the solution with a solution warmer prior to subcutaneous injection of the solution;   applying a sterile sheath to an ultrasonic transducer head of an ultrasound system to protect a skin of the patient from the ultrasonic transducer; and   wherein the solution is subcutaneously injected with an irrigating needle having a blunt tip for delivery of the solution with the therapeutic dose of drug dissolved therein into the treatment field.   
     
     
         10 . The treatment method of  claim 8 , wherein 100 cc of the solution with the therapeutic dose of drug dissolved therein is injected subcutaneously, wherein the therapeutic dose of the drug dissolved in the at least 100 cc of solution is less than a therapeutic dose of the drug required for intravenous injection or for oral administration, and wherein a minimum inhibitory concentration of the drug with respect to the pathogen is more than ten times an drug concentration achievable by intravenous administration. 
     
     
         11 . The treatment method of  claim 8 , wherein the pathogen comprises a  propionibacterium acnes  infection. 
     
     
         12 . The treatment method of  claim 8 , wherein the pathogen comprises a cellulitis infection. 
     
     
         13 . The treatment method of  claim 8 , wherein the pathogen comprises a furuncle. 
     
     
         14 . The treatment method of  claim 8 , wherein the pathogen comprises a carbuncle. 
     
     
         15 . The treatment method of  claim 8 , wherein the pathogen comprises a osteomyelitis. 
     
     
         16 . The treatment method of  claim 8 , wherein the pathogen comprises a methicillin resistant  staphylococcus aureus  infection with a minimum inhibitory concentration of at least 64 micrograms/ml with respect to Cefazolin and wherein the drug comprises Cefazolin. 
     
     
         17 . The treatment method of  claim 8 , wherein the pathogen comprises a methicillin resistant  staphylococcus aureus  infection and wherein the solution includes a reduced therapeutic dose of Vancomycin dissolved therein, the reduced therapeutic dose of Vancomycin being less than the intravenous therapeutic dose of Vancomycin. 
     
     
         18 . A method for treating a wound in tissue of a patient comprising:
 identifying the wound in the tissue of the patient;   injecting a fluid into the tissue that contains the wound and tissue adjacent the wound of the patient;   delivering ultrasound to disperse the fluid throughout the effected tissue and the tissue adjacent the wound to hydrate the tissues with the injected fluid; and   wherein the tissues hydrated with the dispersed fluid accelerates healing of the wound in the tissue.   
     
     
         19 . The method of  claim 18 , wherein the tissue adjacent the wound has insufficient blood supply. 
     
     
         20 . The method of  claim 19 , wherein the tissue adjacent the wound is afflicted with necrotic tissue. 
     
     
         21 . The method of  claim 18 , wherein the wound is closed directly or by grafting or movement of adjacent tissue after delivering ultrasound. 
     
     
         22 . The method of  claim 18 , wherein the wound is surrounded by indurated tissue. 
     
     
         23 . The method of  claim 22 , wherein the indurated tissue is hydrated with the ultrasound dispersed fluid. 
     
     
         24 . The method of  claim 18 , wherein the wound is debrided before delivering of the ultrasound. 
     
     
         25 . The method of  claim 18 , wherein an antibiotic is dissolved in the injected fluid. 
     
     
         26 . The method of  claim 18 , wherein 250 cc of fluid is injected to hydrate the tissue. 
     
     
         27 . The method of  claim 18 , wherein 100 cc of fluid is injected to hydrate the tissue. 
     
     
         28 . A method for treating a tissue area infected with cellulitis of a patient, the method comprising:
 identifying the tissue area infected with cellulitis;   injecting a fluid into the tissue area that is infected with cellulitis;   delivering ultrasound to disperse the fluid throughout the tissue area infected with cellulitis to hydrate the tissue area infected with cellulitis with the injected fluid; and   wherein the tissue area hydrated with the dispersed fluid accelerates healing of the cellulitis infection.   
     
     
         29 . The method of  claim 28 , wherein 250 cc of fluid is injected to hydrate the tissue. 
     
     
         30 . The method of  claim 28 , wherein 100 cc of fluid is injected to hydrate the tissue.