US20150273198A1 - Presurgical treatment methods and systems - Google Patents
Presurgical treatment methods and systems Download PDFInfo
- Publication number
- US20150273198A1 US20150273198A1 US14/738,606 US201514738606A US2015273198A1 US 20150273198 A1 US20150273198 A1 US 20150273198A1 US 201514738606 A US201514738606 A US 201514738606A US 2015273198 A1 US2015273198 A1 US 2015273198A1
- Authority
- US
- United States
- Prior art keywords
- tissue
- antibiotic
- solution
- ultrasound
- patient
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M37/00—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
- A61M37/0092—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin using ultrasonic, sonic or infrasonic vibrations, e.g. phonophoresis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B17/00—Surgical instruments, devices or methods, e.g. tourniquets
- A61B17/32—Surgical cutting instruments
- A61B17/3209—Incision instruments
- A61B17/3211—Surgical scalpels, knives; Accessories therefor
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/54—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame
- A61K31/542—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame ortho- or peri-condensed with heterocyclic ring systems
- A61K31/545—Compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. cephalosporins, cefaclor, or cephalexine
- A61K31/546—Compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. cephalosporins, cefaclor, or cephalexine containing further heterocyclic rings, e.g. cephalothin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
- A61K38/14—Peptides containing saccharide radicals; Derivatives thereof, e.g. bleomycin, phleomycin, muramylpeptides or vancomycin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
- A61N7/00—Ultrasound therapy
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B17/00—Surgical instruments, devices or methods, e.g. tourniquets
- A61B2017/00831—Material properties
- A61B2017/00889—Material properties antimicrobial, disinfectant
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
- A61N7/00—Ultrasound therapy
- A61N2007/0004—Applications of ultrasound therapy
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
- A61N7/00—Ultrasound therapy
- A61N2007/0004—Applications of ultrasound therapy
- A61N2007/0017—Wound healing
Definitions
- the present invention relates to a method of administering antibiotics and related compounds to prevent infection at an open surgical site.
- Prior methods of preventing surgical infection general involve administering either oral, but preferably intravenous doses of antibiotic prior to surgery to provide a systemic dispersion of antibiotic.
- a relatively high dose is required to provide enough antibiotics in the region of exposed tissue that is most susceptible to infection.
- U.S. Pat. No. 6,565,521 discloses a method and system for removing body vessels from a patient for subsequent use in a grafting procedure, such as, for example, saphenous vein graft harvesting for a coronary bypass surgical operation.
- a quantity of a solution is infused into tissue surrounding the portion of the vessel to be removed.
- An external device is used to apply an energy field to the tissue to loosen the intercellular connections between the tissue and the vessel to be removed.
- One such device is an ultrasonic instrument having an ultrasonic transducer comprised of a composite of ultrasonic crystal transducers. Once the energy field has been applied, the portion of the vessel to be removed is separated from surrounding tissue and tributary vessels are ligated. The portion of the vessel is then transected and removed from the body.
- U.S. Pat. No. 6,039,048 (issued to Silberg on Mar. 21, 2000) discloses that antibiotics may be injected with normal saline solution when ultrasonic energy is used to loosen fat tissue prior to removal by liposuction.
- the ultrasonic energy which is transmitted via the saline solution, disrupts connective tissue between fat cells and hence facilitates the removal of the fatty tissue.
- the above and other objects are achieved by providing a process for protecting a surgical site from infection, the process comprising the steps of defining within a surgical or treatment field an incision line, making a first small incision at or about the incision line, injecting a quantity of antibiotic or other therapeutic agent subcutaneously about the incision line via the first small incision, broadcasting ultrasonic energy transcutaneously to disperse the antibiotic agent and fluid subcutaneously, making a second incision along the incision line, the first incision being a fraction of the incision line, but generally no more than 2 mm, and the second incision being along substantially all or the remainder of the incision line.
- FIG. 1 is a flow chart of the method.
- FIG. 2 is a schematic section of a patient showing the first step in the method.
- FIG. 3 is a schematic section of a patient showing the second step in the method.
- FIG. 4 is a schematic section of a patient showing the third step in the method
- FIG. 5 is a schematic section of a patient showing the fourth step in the method.
- FIG. 6 is a plot comparing the time dependence of the serum and tissue concentration of a therapeutic agent.
- FIGS. 1 through 6 wherein like reference numerals refer to like components in the various views, there is illustrated therein a new and improved method for the pre-surgical prophylactic administration of antibiotics and other therapeutic agents, generally denominated 100 herein.
- antibiotics or another therapeutic agents is injected subcutaneously via a small or stab incision using a blunt cannula into the area to be treated.
- High frequency ultrasound energy is broadcast transcutaneously to disperse the antibiotic or other therapeutic agent into the subcutaneous volume to be exposed in surgery by a process of ultrasonic micro streaming. If the area is to be opened, as in surgery, the addition of fluid together with the antibiotic or other therapeutic agent adds extra hydration to the treated area, thus preventing dehydration from exposure during surgery.
- the process is carried out by first defining a surgical or treatment field and the incision line or region 201 thereof.
- the incision line 201 is a reference line, typically drawn on the patient's skin 216 that defines the entire length of the eventual surgical incision.
- the incision line 201 could also represent the region of the body tissue to be exposed during surgery or otherwise most subject to post operative surgical infection.
- a portion of the patient's body 20 in which a surgical procedure is to be performed is shown in section.
- a short stab wound 205 is made at the end of the intended surgical incision line 201 .
- an irrigating cannula 300 comprising a hollow blunt tip 310 is inserted into the short stab wound 205 .
- a solution of fluid containing an antibiotic or related therapeutic agent is delivered through the hollow needle tip 310 of the infusion cannula 300 and is infused into a volume 312 of the tissue underlying the surgical incision line 201 , which will eventually be exposed in the surgical procedure.
- this incision 205 is small the potential for infection through it, while antibiotics are being delivered, is comparatively small.
- the volume 312 of tissue to be infused is determined by the surgical procedure.
- the volume 312 of infusion should include the area surrounding the portion of the tissue that will be exposed and is subject to infection as well as dehydration.
- Suitable isotonic solutions for dissolving an antibiotic agent may be used for infusion, for example, saline or ringer's lactate, with the optional addition of epinephrine or xylocaine.
- the amount of solution may vary depending upon the size of the patient and the area to be infused. Varying degrees of solution infusion are possible while keeping in mind that the infused solution attenuates the ultrasonic energy heating to protect the tissue and provides a greater hydration effect.
- the fluid is preferably warmed to body temperature and is infused in the subcutaneous tissue.
- the cannula 300 is moved externally such that tip of the needle 330 is transport across region 312 dispersing the therapeutic agent therein.
- the cannula tip 310 is moved under the incision line at a rate commensurate with the fluid injection rate to provide an even and uniform does of the agent in the surgical area.
- region 312 is generally at least a substantial portion of the tissue below the intended surgical incision line 201 .
- the depth of the short or stab wound 205 as well as that of region 312 can be just under the skin 216 or deeper, but is generally about 1 cm or less, depending in part on the location of the organ or anatomy requiring surgery, as well as the potential infusion kinetics of the antibiotic agent in the surrounding tissue, as will be further described.
- the physician externally applies ultrasound through the skin over the incision or treatment line region.
- the ultrasonic instrument 400 comprises a handle 410 coupled to a power source 430 , and an ultrasonic transducer head 420 (protected by a sterile sheath) is used to apply ultrasonic energy though the skin 216 of the patient to the volume 312 of tissue which has received the antibiotic agent.
- the ultrasonic transducer in head 420 or elsewhere comprises crystals embedded in a polymer, such as, for example, a lead zirconate titanate crystals embedded in acrylate, that diffuses the energy relatively more superficially than other transducers.
- a transmitting gel is applied to the skin 216 to provide coupling between the ultrasonic transducer head 420 and the patient's skin 216 for the efficient transmission of the ultrasonic waves.
- the physician holds the instrument 430 by the handle 431 and applies the transducer head 432 to the patient's skin 216 , moving the transducer generally over the intended surgical incision line 201 (as in the direction of arrow 401 ) but most generally throughout the area of skin corresponding to the volume 412 of tissue beneath the skin 216 to be treated.
- This volume of tissue 412 (as shown in FIG. 5 .) generally extends down to the deep fascia 413 .
- the ultrasonic field is introduced into the tissue through the skin at a frequency of 1 MHz and a power density of 3 watts/cm2 for a sufficient time for the tissues to become warm and soft generally about 2-5 minutes.
- an ultrasonic frequency of about 0.5 to 5 MHz is used with a power density ranging from about 2.5 to 4 watts/cm2.
- the application of the ultrasonic energy is believed to cause cavitation and microstreaming, i.e., the movement of the fluid in a linear direction away from the ultrasonic energy source.
- the temperature of the site is monitored to prevent excess heat buildup. Should the ultrasonic vibration cause too much heat, the surrounding tissue and skin can be inadvertently damaged.
- the surgical procedure Upon completion of the transcutaneous broadcast of energy in step 140 , the surgical procedure commences with the surgical incision 500 opening to access the surgical site as illustrated in FIG. 5 (corresponding to step 150 of process 100 in FIG. 1 ).
- the surgical incision 500 is made along incision line 201 .
- the ultimate surgical procedure is facilitated by the ultrasonic treatment in combination with the infusion of the fluid super-hydrates the tissue, lessening the effects of tissue dehydration from exposure of the fatty and other tissue to air, as well as the prophylactic effect of the antibiotic agent.
- Alternative energy sources may be used such as other acoustic waves that heat the tissue with pressure from the sound waves, and electromagnetic radiation, such as e.g. light, collimated light, laser or radio frequency energy that is used in a manner that minimizes cell damage while it disperses the antibiotic agent and fluid subcutaneously
- a prophylactic does of the antibiotic Cafazolin was delivery to a patient by the above procedure prior to elective abdominoplasty using the Silberg Tissue Preparation SystemsTM Model ME 800 (9801427) Mettler Surgical, Anaheim, Calif.). About 250 cc of prewarmed saline containing 1 gm of Cefazolin was injected under a surgical incision line 201 that was about 5 cm long. Small sample of adipose tissue where taken during the surgical procedure to determine if the Cefazolin would remain above desired concentration reported by Ohge et al., and thus remain sufficiently high through the procedure. Further, blood serum samples were taken during the procedure to determine the potential for a longer term systemic delivery.
- FIG. 6 which plots the concentration of Cefazolin over time
- FIG. 6 also indicates that the blood serum concentrations of Cefazolin increased to about 10 .mu.g/ml when surgery was completed about an hour later.
- the above method yields antibiotic concentrations in tissue that are far beyond what could be achieved by IV delivery.
- tissue concentrations such as 800 .mu.g/ml
- serum concentration is a significant advantage for antibiotic agents that could be toxic at high systemic concentrations.
- the test data clearly demonstrates that therapeutic levels can be achieved in the target tissues with total doses that are far below the usual systemic dose levels. Even antibiotic such as Vancomycin that is relatively toxic must be brought to sufficient tissue levels to be therapeutic where it is needed. A small fraction of the usual intravenous dose could be given using this method, thus avoiding the toxic effects while treating the patient.
- antibiotics that are encapsulated in vesicles or are formed as nanoparticles, and more preferably those in which ultrasonic energy enhances the dispensing and delivery of the therapeutically active form of the agent.
- MRSA Methicillin-resistant Staphylococcus aureus being a series of strains of this bacterium responsible for difficult-to-treat infections in humans being resistant to a large group of antibiotics called the beta-lactams, which include the penicillins and the cephalosporins. It may also be referred to as multiple-resistant Staphylococcus aureus or oxacillin-resistant Staphylococcus aureus (ORSA).
- RSA oxacillin-resistant Staphylococcus aureus
- .beta.-lactam antibiotics are a broad class of antibiotics that include penicillin derivatives, cephalosporins, monobactams, carbapenems, and .beta.-lactamase inhibitors that is, any antibiotic agent that contains a .beta.-lactam nucleus in its molecular structure, and they are generally considered the most widely-used group of antibiotics.
- the inventive method was first applied prophylactically to a patent to prevent the spread of an MRSA skin infection in non-elective surgery. Surprisingly, not only was a systemic infection by MRSA prevented, but the MRSA in the surgical field of antibiotic saturated tissue visibly cleared of the infection.
- the colony count in the last column is just a quality control measure to insure the correct innooculum.
- inventive method provides a means to achieve the far higher therapeutic levels in the target tissues, with the resulting systemic dose but a small fraction of the amount that is customarily given by other methods, such as Ohge's.
- the inventive procedure allows for the application of antibiotics, that would normally not be thought to be therapeutic against certain microbes, at doses at which they are therapeutic. Further, it has been discovered that despite these high local doses that yield therapeutic effects, the systemic concentration is sufficiently low so as to be likely to avoid side effects that might occur in some patients. The systemic amount is a small fraction of the amount that is customarily given by other methods while attaining far higher therapeutic levels in the target tissues.
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Biomedical Technology (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical & Material Sciences (AREA)
- Epidemiology (AREA)
- Medicinal Chemistry (AREA)
- Heart & Thoracic Surgery (AREA)
- Medical Informatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Surgery (AREA)
- Hematology (AREA)
- Dermatology (AREA)
- Anesthesiology (AREA)
- Gastroenterology & Hepatology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Immunology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Molecular Biology (AREA)
- Radiology & Medical Imaging (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Antibiotics are administered in a surgical site subcutaneously via a small or stab incision in the surgical field. Transcutaneous ultrasonic vibrations are applied across the surgical field, which is then opened in the usual manner, to thereby provide a surgical field which contains a vastly higher and more effective level of antibiotic. At the same time the underlying tissue is hydrated.
Description
- The present application is a Continuation of U.S. Ser. No. 14/725,694 filed May 29, 2015; which is a continuation of U.S. Ser. No. 14/297,110 filed Jun. 5, 2014; which is a continuation of U.S. Ser. No. 13/205,097 filed Aug. 8, 2011 (now U.S. Pat. No. 8,747,384); which is a continuation of U.S. Ser. No. 12/405,616 filed Mar. 17, 2009; which claims the benefit of U.S. Provisional Appln No. 61/096,568 filed on Sep. 12, 2008. The disclosures, all of which are incorporated herein by reference in their entirety for all purposes.
- The present invention relates to a method of administering antibiotics and related compounds to prevent infection at an open surgical site.
- Prior methods of preventing surgical infection general involve administering either oral, but preferably intravenous doses of antibiotic prior to surgery to provide a systemic dispersion of antibiotic.
- However, some patients experience side effects from systemic doses of antibiotics, such as subsequent GI distress due to a change in bacterial flora.
- Moreover, a relatively high dose is required to provide enough antibiotics in the region of exposed tissue that is most susceptible to infection.
- In U.S. Pat. No. 6,565,521 (issued to Silberg on May 20, 2003) discloses a method and system for removing body vessels from a patient for subsequent use in a grafting procedure, such as, for example, saphenous vein graft harvesting for a coronary bypass surgical operation. A quantity of a solution is infused into tissue surrounding the portion of the vessel to be removed. An external device is used to apply an energy field to the tissue to loosen the intercellular connections between the tissue and the vessel to be removed. One such device is an ultrasonic instrument having an ultrasonic transducer comprised of a composite of ultrasonic crystal transducers. Once the energy field has been applied, the portion of the vessel to be removed is separated from surrounding tissue and tributary vessels are ligated. The portion of the vessel is then transected and removed from the body.
- U.S. Pat. No. 6,039,048 (issued to Silberg on Mar. 21, 2000) discloses that antibiotics may be injected with normal saline solution when ultrasonic energy is used to loosen fat tissue prior to removal by liposuction. The ultrasonic energy, which is transmitted via the saline solution, disrupts connective tissue between fat cells and hence facilitates the removal of the fatty tissue.
- However, as the fat cells are removed from the area with the liposuction tube, and no further surgical incisions are made, it is expected that antibiotics are removed with the fat tissue and will not provide a longer term therapeutic effect.
- Accordingly, there is an on-going need for an improved means to administer antibiotic compounds prior to surgery so as to minimize infection.
- It is therefore a first object of the present invention to provide a more effective means for the targeted delivery of antibiotics or other therapeutic agents prior to surgery.
- It is an additional objective of the invention to pre-operatively deliver such antibiotics or therapeutic agents and avoid potential complications and secondary effects of systemic application.
- It is a further object of the invention to provide a higher local concentration of antibiotic in the surgical site which will be open and hence subject to infection, and thus achieve a lower incidence of infection, as well as the faster healing of patients.
- It is still another object of the invention to provide a means to reduce the quantity of antibiotics used pre- and post-operatively.
- It is another object of the invention to also minimize the dehydration of tissues that are exposed during surgery.
- In the present invention, the above and other objects are achieved by providing a process for protecting a surgical site from infection, the process comprising the steps of defining within a surgical or treatment field an incision line, making a first small incision at or about the incision line, injecting a quantity of antibiotic or other therapeutic agent subcutaneously about the incision line via the first small incision, broadcasting ultrasonic energy transcutaneously to disperse the antibiotic agent and fluid subcutaneously, making a second incision along the incision line, the first incision being a fraction of the incision line, but generally no more than 2 mm, and the second incision being along substantially all or the remainder of the incision line.
- The above and other objects, effects, features, and advantages of the present invention will become more apparent from the following description of the embodiments thereof taken in conjunction with the accompanying drawings.
-
FIG. 1 is a flow chart of the method. -
FIG. 2 is a schematic section of a patient showing the first step in the method. -
FIG. 3 is a schematic section of a patient showing the second step in the method. -
FIG. 4 is a schematic section of a patient showing the third step in the method -
FIG. 5 is a schematic section of a patient showing the fourth step in the method. -
FIG. 6 is a plot comparing the time dependence of the serum and tissue concentration of a therapeutic agent. - Referring to
FIGS. 1 through 6 , wherein like reference numerals refer to like components in the various views, there is illustrated therein a new and improved method for the pre-surgical prophylactic administration of antibiotics and other therapeutic agents, generally denominated 100 herein. - In accordance with the present invention, antibiotics or another therapeutic agents is injected subcutaneously via a small or stab incision using a blunt cannula into the area to be treated. High frequency ultrasound energy is broadcast transcutaneously to disperse the antibiotic or other therapeutic agent into the subcutaneous volume to be exposed in surgery by a process of ultrasonic micro streaming. If the area is to be opened, as in surgery, the addition of fluid together with the antibiotic or other therapeutic agent adds extra hydration to the treated area, thus preventing dehydration from exposure during surgery.
- Accordingly, the process is carried out by first defining a surgical or treatment field and the incision line or
region 201 thereof. In thefirst step 110 in theprocess 100, as described in the Flow chart ofFIG. 1 , theincision line 201 is a reference line, typically drawn on the patient'sskin 216 that defines the entire length of the eventual surgical incision. However, as will be more fully understood in light of the further disclose of the method, theincision line 201 could also represent the region of the body tissue to be exposed during surgery or otherwise most subject to post operative surgical infection. - Referring to
FIG. 2 , a portion of the patient'sbody 20 in which a surgical procedure is to be performed is shown in section. In thenext step 120 in theprocess 100, as ashort stab wound 205 is made at the end of the intendedsurgical incision line 201. - In the
next step 130 in theprocess 100, as shown inFIG. 3 , anirrigating cannula 300 comprising a hollowblunt tip 310 is inserted into theshort stab wound 205. A solution of fluid containing an antibiotic or related therapeutic agent is delivered through thehollow needle tip 310 of theinfusion cannula 300 and is infused into avolume 312 of the tissue underlying thesurgical incision line 201, which will eventually be exposed in the surgical procedure. As thisincision 205 is small the potential for infection through it, while antibiotics are being delivered, is comparatively small. - The
volume 312 of tissue to be infused is determined by the surgical procedure. In general, thevolume 312 of infusion should include the area surrounding the portion of the tissue that will be exposed and is subject to infection as well as dehydration. Suitable isotonic solutions for dissolving an antibiotic agent may be used for infusion, for example, saline or ringer's lactate, with the optional addition of epinephrine or xylocaine. The amount of solution may vary depending upon the size of the patient and the area to be infused. Varying degrees of solution infusion are possible while keeping in mind that the infused solution attenuates the ultrasonic energy heating to protect the tissue and provides a greater hydration effect. The fluid is preferably warmed to body temperature and is infused in the subcutaneous tissue. - As shown by the outline of the
needle 310′ and 310″, thecannula 300 is moved externally such that tip of the needle 330 is transport acrossregion 312 dispersing the therapeutic agent therein. Typically thecannula tip 310 is moved under the incision line at a rate commensurate with the fluid injection rate to provide an even and uniform does of the agent in the surgical area. It should be noted thatregion 312 is generally at least a substantial portion of the tissue below the intendedsurgical incision line 201. Thus, the depth of the short or stab wound 205 as well as that ofregion 312 can be just under theskin 216 or deeper, but is generally about 1 cm or less, depending in part on the location of the organ or anatomy requiring surgery, as well as the potential infusion kinetics of the antibiotic agent in the surrounding tissue, as will be further described. - As illustrated in
FIG. 4 , inprocess step 140, after the therapeutic solution is infused instep 130, and removal of thecannula 300 through thefirst incision 205, the physician externally applies ultrasound through the skin over the incision or treatment line region. Theultrasonic instrument 400 comprises ahandle 410 coupled to apower source 430, and an ultrasonic transducer head 420 (protected by a sterile sheath) is used to apply ultrasonic energy though theskin 216 of the patient to thevolume 312 of tissue which has received the antibiotic agent. Preferably the ultrasonic transducer inhead 420 or elsewhere comprises crystals embedded in a polymer, such as, for example, a lead zirconate titanate crystals embedded in acrylate, that diffuses the energy relatively more superficially than other transducers. A transmitting gel is applied to theskin 216 to provide coupling between theultrasonic transducer head 420 and the patient'sskin 216 for the efficient transmission of the ultrasonic waves. The physician holds theinstrument 430 by the handle 431 and applies the transducer head 432 to the patient'sskin 216, moving the transducer generally over the intended surgical incision line 201 (as in the direction of arrow 401) but most generally throughout the area of skin corresponding to thevolume 412 of tissue beneath theskin 216 to be treated. This volume of tissue 412 (as shown inFIG. 5 .) generally extends down to thedeep fascia 413. - In one embodiment, the ultrasonic field is introduced into the tissue through the skin at a frequency of 1 MHz and a power density of 3 watts/cm2 for a sufficient time for the tissues to become warm and soft generally about 2-5 minutes. Preferably an ultrasonic frequency of about 0.5 to 5 MHz is used with a power density ranging from about 2.5 to 4 watts/cm2. The application of the ultrasonic energy is believed to cause cavitation and microstreaming, i.e., the movement of the fluid in a linear direction away from the ultrasonic energy source. Preferably, the temperature of the site is monitored to prevent excess heat buildup. Should the ultrasonic vibration cause too much heat, the surrounding tissue and skin can be inadvertently damaged.
- Upon completion of the transcutaneous broadcast of energy in
step 140, the surgical procedure commences with thesurgical incision 500 opening to access the surgical site as illustrated inFIG. 5 (corresponding to step 150 ofprocess 100 inFIG. 1 ). Thesurgical incision 500 is made alongincision line 201. - The ultimate surgical procedure is facilitated by the ultrasonic treatment in combination with the infusion of the fluid super-hydrates the tissue, lessening the effects of tissue dehydration from exposure of the fatty and other tissue to air, as well as the prophylactic effect of the antibiotic agent.
- Alternative energy sources may be used such as other acoustic waves that heat the tissue with pressure from the sound waves, and electromagnetic radiation, such as e.g. light, collimated light, laser or radio frequency energy that is used in a manner that minimizes cell damage while it disperses the antibiotic agent and fluid subcutaneously
- As reported in “An Additional Dose of Cefazolin for Intraoperative Prophylaxis” Jpn J Surg (1999) 29:1233-1236 , by Ohge et al. it is desirable to provide a tissue level of Cefazolin of about 4 .mu.g/ml) to achieve a minimum inhibitory concentrations (MIC) for 80% (MIC.sub.80) of four bacterial species. The MICs of Cefazolin were determined for 360 isolates of methicillin-sensitive Staphylococcus aureus (MSSA), 204 isolates of Klebsiella pneumoniae, 314 isolates of Escherichia coli, and 30 isolates of Streptococcus spp. In light of these findings, Ohge et al. then pre-operatively treated patients with an intravenous bolus of 1 g of cefazolin was administered over a period of 3-5 minutes at the time of skin incision. Then, 5 ml of peripheral blood, about 3 g of subcutaneous adipose tissue, and peritoneum samples were obtained intraoperatively during and after the procedure. Ohge then discovered that this protocol resulted in a mean tissue concentration of about 10 .mu.g/ml an hour after surgery commenced, but then dropped below 4 .mu.g/ml after slightly more than 2 hours of surgery. During the same time period the serum concentration of Cefazolin decreased from about 80 to 40 .mu.g/ml, and to about 10 .mu.g/ml after about 4 hours.
- A prophylactic does of the antibiotic Cafazolin was delivery to a patient by the above procedure prior to elective abdominoplasty using the Silberg Tissue Preparation Systems™ Model ME 800 (9801427) Mettler Surgical, Anaheim, Calif.). About 250 cc of prewarmed saline containing 1 gm of Cefazolin was injected under a
surgical incision line 201 that was about 5 cm long. Small sample of adipose tissue where taken during the surgical procedure to determine if the Cefazolin would remain above desired concentration reported by Ohge et al., and thus remain sufficiently high through the procedure. Further, blood serum samples were taken during the procedure to determine the potential for a longer term systemic delivery. - As will now be illustrated in
FIG. 6 , which plots the concentration of Cefazolin over time, it has been discovered that this inventive procedure resulted in much higher adipose tissue concentration of Cefazolin at the start of surgery, for the same total dose of 1 gram as used by Ohge. The Cefazolin concentration in the adipose tissue was about 800 .mu.g/ml at the beginning of surgery but dropped about 200 .mu.g/ml about 50 minutes later, achieving about a 50 times greater concentration than was achieved by intravenous administration of Ohge et al. - Further,
FIG. 6 also indicates that the blood serum concentrations of Cefazolin increased to about 10 .mu.g/ml when surgery was completed about an hour later. - Notably, the above method yields antibiotic concentrations in tissue that are far beyond what could be achieved by IV delivery. It should be appreciated that the ability to achieve high tissue concentrations, such as 800 .mu.g/ml, while likely limiting the serum concentration to less than 10 .mu.g/ml, which less than 80.times. the initial tissue saturation and less than about 10 .times. the contemporaneous tissue concentration, is a significant advantage for antibiotic agents that could be toxic at high systemic concentrations. The test data clearly demonstrates that therapeutic levels can be achieved in the target tissues with total doses that are far below the usual systemic dose levels. Even antibiotic such as Vancomycin that is relatively toxic must be brought to sufficient tissue levels to be therapeutic where it is needed. A small fraction of the usual intravenous dose could be given using this method, thus avoiding the toxic effects while treating the patient.
- It should be understood that at least one species of antibiotic agents contemplated by the various embodiments of the invention includes antibiotics that are encapsulated in vesicles or are formed as nanoparticles, and more preferably those in which ultrasonic energy enhances the dispensing and delivery of the therapeutically active form of the agent.
- It has further been discovered the above method also provide a means to treat patients with MRSA skin infections with antibiotics thought to be ineffective.
- MRSA stands for Methicillin-resistant Staphylococcus aureus being a series of strains of this bacterium responsible for difficult-to-treat infections in humans being resistant to a large group of antibiotics called the beta-lactams, which include the penicillins and the cephalosporins. It may also be referred to as multiple-resistant Staphylococcus aureus or oxacillin-resistant Staphylococcus aureus (ORSA). .beta.-lactam antibiotics are a broad class of antibiotics that include penicillin derivatives, cephalosporins, monobactams, carbapenems, and .beta.-lactamase inhibitors that is, any antibiotic agent that contains a .beta.-lactam nucleus in its molecular structure, and they are generally considered the most widely-used group of antibiotics.
- The inventive method was first applied prophylactically to a patent to prevent the spread of an MRSA skin infection in non-elective surgery. Surprisingly, not only was a systemic infection by MRSA prevented, but the MRSA in the surgical field of antibiotic saturated tissue visibly cleared of the infection.
- Accordingly, further tests of Cephazolin with a range of different MRSA strains at concentrations well above the dose achievable by IV delivery were made to understand these finding. The Minimum inhibitory concentration (MIC) of Cephazolin with respect to these various strains is reported below in Table 1 in units are in .mu.g/ml of Cefazolin using the broth dilution method. MIC is the lowest concentration of an antimicrobial that will inhibit the visible growth of a microorganism after overnight incubation. STA 29213 is the conventional strain of S. aureus, showing normal sensitivity to Cefazolin with an MIC of 0.5 .mu.g/ml.
-
TABLE 1 MIC/ Median Colony Organism Cefazolin MIC, μg/ml Count MRSA 143 64 128 5.73E+05 128 4.18E+05 128 5.94E+05 MRSA 144 128 64 5.12E+05 64 4.43E+05 64 5.15E+05 MRSA 145 128 128 4.87E+05 128 7.50E+05 128 7.54E+05 MRSA 146 64 64 5.79E+05 64 4.62E+05 128 5.68E+05 MRSA 147 64 64 5.22E+05 64 3.71E+05 64 6.83E+05 MRSA 148 256 256 3.45E+05 256 4.30E+05 128 4.37E+05 MRSA 149 128 128 4.93E+05 128 6.97E+05 128 5.28E+05 MRSA 150 512 512 4.67E+05 512 5.08E+05 512 4.92E+05 MRSA 151 128 128 3.66E+05 128 4.91E+05 128 4.54E+05 MRSA 152 4 4 4.03E+05 4 4.44E+05 8 5.55E+05 STA 29213 0.5 3.02E+05 MSSA 1 5.63E+05 MRSA 56 64 128 2.04E+05 (494) 128 5.84E+05 128 6.32E+05 MRSA 116 512 256 7.40E+05 256 6.32E+05 256 5.24E+05 MRSA 142 256 256 4.42E+05 ATCC 33591 256 5.26E+05 MRSA 256 5.18E+05 Mu 3 512 512 3.52E+05 MRSA 512 4.20E+05 hVISA 512 4.42E+05 Mu 50 256 256 5.98E+05 MRSA 256 2.68E+05 VISA 256 2.70E+05 STA 25923 0.5 0.5 5.72E+05 MSSA 0.5 5.76E+05 0.5 5.82E+05 STA 29213 0.5 0.5 4.04E+05 MSSA 0.5 3.94E+05 0.5 5.88E+05 - The colony count in the last column is just a quality control measure to insure the correct innooculum.
- First, it should be noted that many of these strains, being antibiotic resistant, have an MIC more than 10.times. the 10 .mu.g/ml in tissue achieved by Ohge via pre-operative IV administration. However, the most resistant strain, MU 3, has an MIC of about 512 .mu.g/ml, about 50.times. the dose required for normal strains. The inventive method of antibiotic administration results in much higher concentrations in tissue of at least the 800 .mu.g/ml reported above.
- It has now been discovered, inventive method provides a means to achieve the far higher therapeutic levels in the target tissues, with the resulting systemic dose but a small fraction of the amount that is customarily given by other methods, such as Ohge's.
- It should also be apparent based on the above teaching that agents to reduce pain, inflammation in joints, and to infiltrate soft tissue tumors, could be administered using this technique and have the same benefit-safety ratio.
- It has been discovered that the inventive procedure allows for the application of antibiotics, that would normally not be thought to be therapeutic against certain microbes, at doses at which they are therapeutic. Further, it has been discovered that despite these high local doses that yield therapeutic effects, the systemic concentration is sufficiently low so as to be likely to avoid side effects that might occur in some patients. The systemic amount is a small fraction of the amount that is customarily given by other methods while attaining far higher therapeutic levels in the target tissues.
- While the invention has been described with reference to particular embodiments, it will be understood to one skilled in the art that variations and modifications may be made in form and detail without departing from the spirit and scope of the invention. Such modifications may include substituting other elements, components or structures that the invention can be practiced with modification within the scope of the following claims.
Claims (25)
1. A method of reducing an incidence of infection in a patient at a surgical site associated with a surgical procedure, the method comprising:
identifying a region of tissue of the patient that will be exposed during the surgical procedure;
subcutaneously introducing a solution comprising a dose of a drug dissolved therein through a skin of the patient at a location to or in a vicinity of the identified region of tissue;
applying ultrasound transcutaneously toward the identified region of tissue and the subcutaneously introduced solution, wherein the transcutaneously applied ultrasound interacts with the solution to disperse the solution with the dose of drug dissolved therein through the identified region of tissue;
exposing the identified region of tissue to air; and
performing the surgical procedure.
2. The method of claim 1 , further comprising making a stab wound in the skin at the location prior to subcutaneously introducing the solution to or in a vicinity of the identified region of tissue.
3. The method of claim 2 , wherein the solution is subcutaneously introduced using an irrigating needle having a blunt tip that is inserted into the patient through the stab wound in the skin at the location.
4. The method of claim 2 , wherein the stab wound is 1 cm or less in depth.
5. The method of claim 2 , wherein exposing the identified region of tissue to air comprises performing a surgical incision along the skin of the patient.
6. The method of claim 5 , wherein the stab wound is along the surgical incision path.
7. The method of claim 1 , wherein at least 250 cc of solution is subcutaneously introduced through the skin of the patient.
8. The method of claim 1 , wherein the antibiotic comprises a β-lactam antibiotic.
9. The method of claim 8 , wherein the antibiotic comprises a penicillin or a cephalosporin.
10. The method of claim 1 , wherein the ultrasound is transcutaneously 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.
11. A method of open surgery, the method comprising:
identifying a tissue site of the patient that will be exposed during the open surgery;
preparing a tissue site for the open surgery by:
subcutaneously introducing a solution comprising a dose of an antibiotic dissolved therein through a skin of the patient at a location to or in a vicinity of the identified tissue site;
applying ultrasound transcutaneously toward the identified tissue site and the subcutaneously introduced solution, wherein the transcutaneously applied ultrasound interacts with the solution to disperse the solution with the dose of antibiotic dissolved therein through the identified region of tissue, the dose of antibiotic dissolved in the solution being dispersed through the infected tissue at therapeutically effective concentrations for reducing an incidence of infection at the identified region of tissue during the open surgery.
12. The method of claim 11 , wherein the antibiotic comprises a β-lactam antibiotic.
13. The method of claim 12 , wherein the antibiotic comprises a penicillin or a cephalosporin.
14. The method of claim 11 , wherein the ultrasound is transcutaneously 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.
15. The method of claim 11 , wherein the concentration of the antibiotic in the tissue is therapeutically effective for reducing the incidence of infection while the maintaining of a serum concentration to less than 10 micrograms/ml one hour after the application of transcutaneous ultrasound, wherein maintaining the serum concentration to less than 10 micrograms/ml one hour after the application of transcutaneous ultrasound reduces adverse side effects to bacterial flora in a gastrointestinal tract of the patient.
16. The method of claim 11 , wherein side effects associated with systemic application of the antibiotic are avoided.
17. A system for preparing a tissue site of a patient for an open surgery procedure, the system comprising:
a cannula for subcutaneously injecting a solution with a dose of an antibiotic dissolved therein to a tissue site of the patient that will be exposed to air during the open surgery;
an ultrasound system configured to broadcast ultrasound transcutaneously toward the identified tissue and the subcutaneously injected solution, wherein the ultrasound system is configured to broadcast ultrasound at a power density of 2.5 to 4 W/cm2 and at a frequency of less than 5 MHz that is configured to interact with the subcutaneously injected solution to disperse the subcutaneously injected solution with the dose of antibiotic dissolved therein through the tissue at a concentration; and wherein the concentration of antibiotic in the identified tissue is therapeutically effective for reducing an incidence of infection at the identified tissue during the open surgery.
18. The system of claim 17 , further comprising the solution with the dose of antibiotic, wherein the dose of the antibiotic dissolved therein is less than a dose of the antibiotic required for intravenous injection or for oral administration.
19. The system of claim 17 , further comprising 250 cc of the solution with the antibiotic dissolved therein.
20. The system of claim 17 , wherein the concentration of antibiotic in the tissue is therapeutically effective for reducing an incidence of infection at the identified tissue during the open surgery while maintaining serum concentration of the antibiotic to less than 10 micrograms/ml one hour after the application of the transcutaneous ultrasound.
21. The system of claim 17 , wherein the ultrasound system is configured to broadcast ultrasound transcutaneously toward the identified tissue for five minutes or less.
22. The system of claim 17 , further comprising a temperature monitor for preventing inadvertent heat damage to a skin of the patient during the broadcast of transcutaneous ultrasound.
23. The system of claim 17 , wherein the solution is dispersed by microstreaming.
24. The system of claim 17 , wherein the solution is dispersed by cavitation.
25. The system of claim 17 , wherein the broadcasted ultrasound disperses the dose of antibiotic through the tissue at a concentration of at least 200 micrograms/ml fifty minutes after the broadcast of transcutaneous ultrasound.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US14/738,606 US20150273198A1 (en) | 2008-09-12 | 2015-06-12 | Presurgical treatment methods and systems |
Applications Claiming Priority (6)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US9656808P | 2008-09-12 | 2008-09-12 | |
US12/405,616 US20100069827A1 (en) | 2008-09-12 | 2009-03-17 | Pre-Surgical Prophylactic Administration of Antibiotics and Therapeutic Agents |
US13/205,097 US8747384B2 (en) | 2008-09-12 | 2011-08-08 | Administration of antibiotics and therapeutic agents |
US14/297,110 US11197987B2 (en) | 2008-09-12 | 2014-06-05 | Administration of antibiotics and therapeutic agents |
US14/725,694 US10099045B2 (en) | 2008-09-12 | 2015-05-29 | Administration of antibiotics and therapeutic agents |
US14/738,606 US20150273198A1 (en) | 2008-09-12 | 2015-06-12 | Presurgical treatment methods and systems |
Related Parent Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US14/725,694 Continuation US10099045B2 (en) | 2008-09-12 | 2015-05-29 | Administration of antibiotics and therapeutic agents |
Publications (1)
Publication Number | Publication Date |
---|---|
US20150273198A1 true US20150273198A1 (en) | 2015-10-01 |
Family
ID=42007845
Family Applications (5)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US12/405,616 Abandoned US20100069827A1 (en) | 2008-09-12 | 2009-03-17 | Pre-Surgical Prophylactic Administration of Antibiotics and Therapeutic Agents |
US13/205,097 Active 2029-07-22 US8747384B2 (en) | 2008-09-12 | 2011-08-08 | Administration of antibiotics and therapeutic agents |
US14/297,110 Active 2029-06-13 US11197987B2 (en) | 2008-09-12 | 2014-06-05 | Administration of antibiotics and therapeutic agents |
US14/725,694 Active US10099045B2 (en) | 2008-09-12 | 2015-05-29 | Administration of antibiotics and therapeutic agents |
US14/738,606 Abandoned US20150273198A1 (en) | 2008-09-12 | 2015-06-12 | Presurgical treatment methods and systems |
Family Applications Before (4)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US12/405,616 Abandoned US20100069827A1 (en) | 2008-09-12 | 2009-03-17 | Pre-Surgical Prophylactic Administration of Antibiotics and Therapeutic Agents |
US13/205,097 Active 2029-07-22 US8747384B2 (en) | 2008-09-12 | 2011-08-08 | Administration of antibiotics and therapeutic agents |
US14/297,110 Active 2029-06-13 US11197987B2 (en) | 2008-09-12 | 2014-06-05 | Administration of antibiotics and therapeutic agents |
US14/725,694 Active US10099045B2 (en) | 2008-09-12 | 2015-05-29 | Administration of antibiotics and therapeutic agents |
Country Status (1)
Country | Link |
---|---|
US (5) | US20100069827A1 (en) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US10258782B2 (en) | 2014-06-04 | 2019-04-16 | Sonescence, Inc. | Systems and methods for therapeutic agent delivery |
Families Citing this family (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US11213481B2 (en) | 2004-06-25 | 2022-01-04 | Hk Pharma | Tumescent drug delivery |
US20100069827A1 (en) | 2008-09-12 | 2010-03-18 | Barry Neil Silberg | Pre-Surgical Prophylactic Administration of Antibiotics and Therapeutic Agents |
US9446227B2 (en) | 2008-09-12 | 2016-09-20 | Sonescence, Inc. | Ultrasonic dispersion of compositions in tissue |
CN102781509A (en) | 2009-11-30 | 2012-11-14 | 杰弗里·艾伦·克莱因 | Tumescent antibiotic solution |
Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6565521B1 (en) * | 2001-11-30 | 2003-05-20 | Silberg Barry N | System and method of vessel removal |
US20050054098A1 (en) * | 2003-06-27 | 2005-03-10 | Sanjay Mistry | Postpartum cells derived from umbilical cord tissue, and methods of making and using the same |
US20050058729A1 (en) * | 1993-05-19 | 2005-03-17 | Staggs Jeff J. | Treatment for bacterial infections and related disorders |
US20060222692A1 (en) * | 2005-03-31 | 2006-10-05 | Fairfield Clinical Trials Llc | Method and compositions for transdermal administration of antimicrobial medications |
US20070213688A1 (en) * | 2003-05-21 | 2007-09-13 | Klein Jeffrey A | Infiltration cannula |
US20080255055A1 (en) * | 2004-11-10 | 2008-10-16 | Neobiotics Ab | Use of Derivatives of Dipeptides for the Manufacture of of a Medicament for the Treamtent of Microbial Infections |
Family Cites Families (51)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3630198A (en) | 1969-06-23 | 1971-12-28 | Henkin Melvyn Lane | Catheter placement device |
US4190495A (en) | 1976-09-27 | 1980-02-26 | Research Corporation | Modified microorganisms and method of preparing and using same |
DE2861413D1 (en) * | 1977-10-13 | 1982-01-28 | Sanraku Ocean Co | Thienamycin related antibiotics ps-6 and ps-7, process for their production and compositions containing them |
US4982730A (en) * | 1988-12-21 | 1991-01-08 | Lewis Jr Royce C | Ultrasonic wound cleaning method and apparatus |
US5580575A (en) * | 1989-12-22 | 1996-12-03 | Imarx Pharmaceutical Corp. | Therapeutic drug delivery systems |
US5016615A (en) * | 1990-02-20 | 1991-05-21 | Riverside Research Institute | Local application of medication with ultrasound |
US5197946A (en) | 1990-06-27 | 1993-03-30 | Shunro Tachibana | Injection instrument with ultrasonic oscillating element |
JP3319800B2 (en) * | 1993-02-01 | 2002-09-03 | 辻本化学工業株式会社 | Anti-resistant Staphylococcus aureus compounds |
RU2119769C1 (en) | 1993-03-12 | 1998-10-10 | Александр Николаевич Лищенко | Method for treating acute pancreatitis |
US5814599A (en) * | 1995-08-04 | 1998-09-29 | Massachusetts Insitiute Of Technology | Transdermal delivery of encapsulated drugs |
US7083572B2 (en) | 1993-11-30 | 2006-08-01 | Bristol-Myers Squibb Medical Imaging, Inc. | Therapeutic delivery systems |
DE69527195T2 (en) | 1994-01-14 | 2003-03-06 | Xoma Technology Ltd., Berkeley | ANTI GRAM POSITIVE BACTERIAL PROCESS AND MEANS |
US5559108A (en) * | 1994-09-02 | 1996-09-24 | Bristol-Myers Squibb Company | Cephalosporin derivatives |
US6176842B1 (en) * | 1995-03-08 | 2001-01-23 | Ekos Corporation | Ultrasound assembly for use with light activated drugs |
US5980549A (en) | 1995-07-13 | 1999-11-09 | Origin Medsystems, Inc. | Tissue separation cannula with dissection probe and method |
US6041253A (en) * | 1995-12-18 | 2000-03-21 | Massachusetts Institute Of Technology | Effect of electric field and ultrasound for transdermal drug delivery |
US6228082B1 (en) | 1995-11-22 | 2001-05-08 | Arthrocare Corporation | Systems and methods for electrosurgical treatment of vascular disorders |
US5928135A (en) | 1996-08-15 | 1999-07-27 | Ethicon Endo-Surgery, Inc. | Method and devices for endoscopic vessel harvesting |
US6074657A (en) | 1997-03-20 | 2000-06-13 | Pharmacia & Upjohn Company | Administration of an injectable antibiotic in the ear of an animal |
US6120751A (en) | 1997-03-21 | 2000-09-19 | Imarx Pharmaceutical Corp. | Charged lipids and uses for the same |
US5884631A (en) * | 1997-04-17 | 1999-03-23 | Silberg; Barry | Body contouring technique and apparatus |
US6464680B1 (en) * | 1998-07-29 | 2002-10-15 | Pharmasonics, Inc. | Ultrasonic enhancement of drug injection |
US5980512A (en) * | 1998-02-26 | 1999-11-09 | Silberg; Barry | Enhanced laser skin treatment mechanism |
US6030374A (en) * | 1998-05-29 | 2000-02-29 | Mcdaniel; David H. | Ultrasound enhancement of percutaneous drug absorption |
US6039048A (en) * | 1998-04-08 | 2000-03-21 | Silberg; Barry | External ultrasound treatment of connective tissue |
US6484052B1 (en) * | 1999-03-30 | 2002-11-19 | The Regents Of The University Of California | Optically generated ultrasound for enhanced drug delivery |
IL131623A0 (en) * | 1999-08-27 | 2001-01-28 | Dan Weiss | Apparatus to couple ultrasonic energy to catheters and other transdermal medical devices |
WO2001022897A1 (en) * | 1999-09-28 | 2001-04-05 | Novasys Medical, Inc. | Treatment of tissue by application of energy and drugs |
RU2175565C2 (en) | 1999-12-06 | 2001-11-10 | Лоцманов Юрий Александрович | Method for treating chronic tonsillitis |
DE20019711U1 (en) * | 2000-11-20 | 2002-04-04 | Söring GmbH, 25451 Quickborn | Ultrasound device for the treatment of septic wounds |
US6569099B1 (en) | 2001-01-12 | 2003-05-27 | Eilaz Babaev | Ultrasonic method and device for wound treatment |
US20020099356A1 (en) | 2001-01-19 | 2002-07-25 | Unger Evan C. | Transmembrane transport apparatus and method |
US6623444B2 (en) * | 2001-03-21 | 2003-09-23 | Advanced Medical Applications, Inc. | Ultrasonic catheter drug delivery method and device |
EP1443944A1 (en) * | 2001-11-12 | 2004-08-11 | Johannes Reinmüller | Pharmaceutical applications of hyaluronic acid preparations |
RU2218886C2 (en) | 2001-12-06 | 2003-12-20 | Новиков Алексей Алексеевич | Method for setting large articulation prostheses |
RU2320381C2 (en) | 2001-12-28 | 2008-03-27 | Владимир Павлович Жаров | Photo-ultrasonic device |
US7374551B2 (en) | 2003-02-19 | 2008-05-20 | Pittsburgh Plastic Surgery Research Associates | Minimally invasive fat cavitation method |
US20040220551A1 (en) | 2003-04-30 | 2004-11-04 | Flaherty J. Christopher | Low profile components for patient infusion device |
GB2415372A (en) | 2004-06-23 | 2005-12-28 | Destiny Pharma Ltd | Non photodynamical or sonodynamical antimicrobial use of porphyrins and azaporphyrins containing at least one cationic-nitrogen-containing substituent |
US20060247601A1 (en) * | 2005-04-19 | 2006-11-02 | Ellin Philip J | Method of improved drug delivery and for treatment of cellulitis |
US7981442B2 (en) | 2005-06-28 | 2011-07-19 | University Of South Florida | Ultrasound enhancement of drug release across non-ionic surfactant membranes |
US8050752B2 (en) | 2006-09-29 | 2011-11-01 | Bacoustics, Llc | Method of treating lumens, cavities, and tissues of the body with an ultrasound delivered liquid |
US20100069827A1 (en) | 2008-09-12 | 2010-03-18 | Barry Neil Silberg | Pre-Surgical Prophylactic Administration of Antibiotics and Therapeutic Agents |
GB0820377D0 (en) | 2008-11-07 | 2008-12-17 | Isis Innovation | Mapping and characterization of cavitation activity |
CN102470100B (en) | 2009-07-31 | 2015-02-18 | 皇家飞利浦电子股份有限公司 | Method for the preparation of microparticles with efficient bioactive molecule incorporation |
GB0916634D0 (en) | 2009-09-22 | 2009-11-04 | Isis Innovation | Ultrasound systems |
GB0916635D0 (en) | 2009-09-22 | 2009-11-04 | Isis Innovation | Ultrasound systems |
GB201019434D0 (en) | 2010-11-17 | 2010-12-29 | Isis Innovation | Sonosensitive nanoparticles |
SG11201506154RA (en) | 2013-03-14 | 2015-09-29 | Ekos Corp | Method and apparatus for drug delivery to a target site |
GB201318668D0 (en) | 2013-10-22 | 2013-12-04 | Isis Innovation | Sonosensitive therapeutic |
GB201320413D0 (en) | 2013-11-19 | 2014-01-01 | Isis Innovation | Cavitation-inducing polymeric nanoparticles |
-
2009
- 2009-03-17 US US12/405,616 patent/US20100069827A1/en not_active Abandoned
-
2011
- 2011-08-08 US US13/205,097 patent/US8747384B2/en active Active
-
2014
- 2014-06-05 US US14/297,110 patent/US11197987B2/en active Active
-
2015
- 2015-05-29 US US14/725,694 patent/US10099045B2/en active Active
- 2015-06-12 US US14/738,606 patent/US20150273198A1/en not_active Abandoned
Patent Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20050058729A1 (en) * | 1993-05-19 | 2005-03-17 | Staggs Jeff J. | Treatment for bacterial infections and related disorders |
US6565521B1 (en) * | 2001-11-30 | 2003-05-20 | Silberg Barry N | System and method of vessel removal |
US20070213688A1 (en) * | 2003-05-21 | 2007-09-13 | Klein Jeffrey A | Infiltration cannula |
US20050054098A1 (en) * | 2003-06-27 | 2005-03-10 | Sanjay Mistry | Postpartum cells derived from umbilical cord tissue, and methods of making and using the same |
US20080255055A1 (en) * | 2004-11-10 | 2008-10-16 | Neobiotics Ab | Use of Derivatives of Dipeptides for the Manufacture of of a Medicament for the Treamtent of Microbial Infections |
US20060222692A1 (en) * | 2005-03-31 | 2006-10-05 | Fairfield Clinical Trials Llc | Method and compositions for transdermal administration of antimicrobial medications |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US10258782B2 (en) | 2014-06-04 | 2019-04-16 | Sonescence, Inc. | Systems and methods for therapeutic agent delivery |
US11129977B2 (en) | 2014-06-04 | 2021-09-28 | Sonescence, Inc. | Systems and methods for therapeutic agent delivery |
Also Published As
Publication number | Publication date |
---|---|
US8747384B2 (en) | 2014-06-10 |
US20140288483A1 (en) | 2014-09-25 |
US11197987B2 (en) | 2021-12-14 |
US20110301528A1 (en) | 2011-12-08 |
US20150258320A1 (en) | 2015-09-17 |
US10099045B2 (en) | 2018-10-16 |
US20100069827A1 (en) | 2010-03-18 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US10099045B2 (en) | Administration of antibiotics and therapeutic agents | |
Lugo et al. | Septic arthritis, tenosynovitis, and infections of hoof structures | |
Bapat et al. | Experience with vacuum‐assisted closure of sternal wound infections following cardiac surgery and evaluation of chronic complications associated with its use | |
Imperiale et al. | Abscesses of the breast: US-guided serial percutaneous aspiration and local antibiotic therapy after unsuccessful systemic antibiotic therapy | |
Mason et al. | Costs and complications of equine castration: a UK practice‐based study comparing ‘standing nonsutured’and ‘recumbent sutured’techniques | |
Tewarie et al. | Effective combination of different surgical strategies for deep sternal wound infection and mediastinitis | |
Troy et al. | Do topical antibiotics provide improved prophylaxis against bacterial growth in the presence of polypropylene mesh? | |
Kocherry et al. | Efficacy of stereotactic aspiration in deep-seated and eloquent-region intracranial pyogenic abscesses | |
Orsini | Meta-analysis of clinical factors affecting synovial structure infections and prognosis | |
Mader et al. | The principles of the use of preventive antibiotics. | |
Nishida et al. | Postoperative mediastinitis: a comparison of two electrocautery techniques on presternal soft tissues | |
Hemal et al. | Retroperitoneoscopic Managementof Infected Cysts in Adult Polycystic Kidney Disease | |
Comino et al. | Standing laparoscopy combined with a conventional inguinal approach to treat extended septic funiculitis in 12 horses | |
Kyoda et al. | Decrease in incidence of surgical site infections in contemporary series of patients with radical cystectomy | |
US20190070398A1 (en) | Ultrasonic Dispersion of Compositions in Tissue | |
Kusachi et al. | Antibiotic time-lag combination therapy with fosfomycin for postoperative intra-abdominal abscesses | |
US8933068B2 (en) | Composition and methods of treatment of bacterial meningitis | |
Celikoglu et al. | Techniques for intratumoral chemotherapy of lung cancer by bronchoscopic drug delivery. | |
Heard et al. | PMMA bead versus parenteral treatment of Staphylococcus aureus osteomyelitis | |
Strickland et al. | The increased incidence of intraabdominal infections in laparoscopic procedures: potential causes, postoperative management, and prospective innovations | |
CN101374532A (en) | Use of gallium to treat biofilm-associated infectons | |
Schwieder et al. | Successful transabdominal treatment of a chronic splenic abscess caused by Clostridium perfringens after penetrating external trauma in a horse | |
RU2228145C2 (en) | Method for preventing infectious inflammatory and thrombohemorrhagic complications in patients operated for benign prostate hyperplasia | |
RU2250104C2 (en) | Medium in case of ultrasound cavitary treatment of wounds | |
Watts | How to select cases and perform field technique for regional limb perfusion. |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
AS | Assignment |
Owner name: SONESCENCE, INC., CALIFORNIA Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:SILBERG, BARRY NEIL;REEL/FRAME:035831/0271 Effective date: 20150108 |
|
STPP | Information on status: patent application and granting procedure in general |
Free format text: NON FINAL ACTION MAILED |
|
STPP | Information on status: patent application and granting procedure in general |
Free format text: FINAL REJECTION MAILED |
|
STCB | Information on status: application discontinuation |
Free format text: ABANDONED -- FAILURE TO RESPOND TO AN OFFICE ACTION |