US20080274097A1 - Booster for therapy of diseases with ultrasound and pharmaceutical liquid composition containing the same - Google Patents
Booster for therapy of diseases with ultrasound and pharmaceutical liquid composition containing the same Download PDFInfo
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- US20080274097A1 US20080274097A1 US12/172,686 US17268608A US2008274097A1 US 20080274097 A1 US20080274097 A1 US 20080274097A1 US 17268608 A US17268608 A US 17268608A US 2008274097 A1 US2008274097 A1 US 2008274097A1
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- medicament
- booster
- liquid composition
- ultrasound
- pharmaceutical liquid
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- 239000003814 drug Substances 0.000 claims abstract description 54
- 238000000034 method Methods 0.000 claims description 23
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Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K41/00—Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
- A61K41/0028—Disruption, e.g. by heat or ultrasounds, sonophysical or sonochemical activation, e.g. thermosensitive or heat-sensitive liposomes, disruption of calculi with a medicinal preparation and ultrasounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K41/00—Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
- A61K41/0004—Homeopathy; Vitalisation; Resonance; Dynamisation, e.g. esoteric applications; Oxygenation of blood
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K41/00—Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
- A61K41/0047—Sonopheresis, i.e. ultrasonically-enhanced transdermal delivery, electroporation of a pharmacologically active agent
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/22—Echographic preparations; Ultrasound imaging preparations ; Optoacoustic imaging preparations
- A61K49/222—Echographic preparations; Ultrasound imaging preparations ; Optoacoustic imaging preparations characterised by a special physical form, e.g. emulsions, liposomes
- A61K49/223—Microbubbles, hollow microspheres, free gas bubbles, gas microspheres
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0002—Galenical forms characterised by the drug release technique; Application systems commanded by energy
- A61K9/0009—Galenical forms characterised by the drug release technique; Application systems commanded by energy involving or responsive to electricity, magnetism or acoustic waves; Galenical aspects of sonophoresis, iontophoresis, electroporation or electroosmosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/5005—Wall or coating material
- A61K9/5021—Organic macromolecular compounds
- A61K9/5052—Proteins, e.g. albumin
Definitions
- This invention relates to a booster useful for enhancing the effects of ultrasound in the therapy of various diseases and a pharmaceutical liquid composition containing the booster and a medicament which shows enhanced diffusion and penetration of the medicament into the body by applying ultrasound. More particularly, it relates to a booster useful for therapy of various disease by applying ultrasound which comprises a plurality of microbubbles of a gas in a liquid, a pharmaceutical liquid composition comprising a plurality of microbubbles of a gas and a medicament in a liquid, and the use thereof in the therapy of various diseases while applying ultrasound.
- the present inventors have intensively studied enhancing the effects of ultrasound at a lower energy of an ultrasonic vibration and have found that a booster comprising a plurality of microbubbles of a gas in a liquid is useful for the desired enhancement of the effects of ultrasound.
- An object of the invention is to provide a booster useful for enhancing the effects of ultrasound which comprises a plurality of microbubbles of a gas in a liquid.
- Another object of the invention is to provide a pharmaceutical liquid composition containing the booster and a medicament which is useful for the therapy of various diseases together with the application of ultrasound.
- a further object of the invention is to provide a method for enhancing the effects by the application of ultrasound in the therapy of various diseases which comprises injecting the booster or the pharmaceutical liquid composition as set forth above into the portion to be remedied while applying ultrasound thereto.
- FIG. 1 shows a schematic view of one of the microbubbles contained in the booster of the invention.
- FIG. 2 shows a schematic sectional view of one embodiment of a drug administration device used for injecting, pouring, applying or circulating the booster or the pharmaceutical liquid composition of the invention.
- FIG. 3 shows a schematic sectional view of one embodiment of a drug administration device used for transdermal administration of the booster or the pharmaceutical liquid composition of the invention.
- FIG. 4 and FIG. 5 show graphs showing fibrinolysis by application of ultrasound with or without the booster of the invention.
- the booster of the invention comprises a liquid containing a plurality of microbubbles of a gas having a diameter of 0.1 to 100 ⁇ m.
- the microbubbles are formed by entrapping microspheres of a gas into a liquid.
- the booster contains, for example, about 4 ⁇ 10 7 of the microbubbles per one milliliter of a liquid.
- the microbubbles are made of various gases such as air, oxygen gas, carbon dioxide gas, inert gases (e.g. xenon, krypton, argon, neon, helium, etc.), preferably air and oxygen gas.
- the liquid includes any liquid which can form microbubbles, for example, human serum albumin (e.g.
- the booster can be prepared by a known method, for example, by agitating the liquid as mentioned above while blowing a gas as mentioned above into the liquid, or alternatively exposing the liquid to ultrasound with a sonicator under a gaseous atmosphere, whereby a vibration is applied to the liquid to form microbubbles of the gas.
- the pharmaceutical liquid composition of the invention comprises a plurality of microbubbles of a gas and a medicament in a liquid.
- the microbubbles of a gas and liquid are the same as mentioned above.
- anti-thrombosis agents e.g. urokinase, tissue plasminogen activator, etc.
- hormones e.g. insulin, etc.
- theophylline plasminogen activator
- lidocaine e.g.
- the medicament can be contained in a therapeutically effective amount as usually used.
- the pharmaceutical liquid composition can be prepared by mixing a medicament with a booster comprising a plurality of microbubbles of a gas in a liquid.
- the mixing ratio may vary depending on the desired amount and kind of the medicament and the kind of the liquid, but is usually in a range of 1:100 to 100:1 by weight (a medicament/a booster).
- the therapeutic effect of ultrasound is boosted by the presence of a booster of the invention.
- a pharmaceutical liquid composition containing the booster and a medicament is poured or injected into a body in parenteral routes, such as intravenously, percutaneously or intramuscularly, while applying thereto an ultrasonic vibration
- the therapeutic effects of the medicament is significantly enhanced.
- an ultrasound from an ultrasonic element is applied to the liquid containing the booster and medicament
- cavitation occurs in the liquid composition, and the medicament is diffused and penetrated into the desired portion of the biobody by the aid of vibration induced by the cavitation.
- the cavitation occurs when the level of vibration energy exceeds a certain threshold value.
- the threshold value of the vibration energy is reduced due to the presence of a plurality of microbubbles of a gas. That is, the microbubbles of a gas act as nucleus of cavitation and thereby the cavitation occurs more easily. Therefore, according to the invention, the desired ultrasonic energy necessary for the desired diffusion and penetration of a medicament is reduced.
- the desired ultrasound is applied by conventional ultrasonic devices which can supply an ultrasonic signal of 20 KHz to several MHz.
- FIG. 1 shows a schematic view of one of the plurality of microbubbles of a gas contained in the booster of the invention, wherein the microbubble of a gas has a diameter of 0.1 to 100 ⁇ m and is composed of a shell of human serum albumin 1 and gas 2 entrapped within the microbubble.
- the microbubbles are contained in a liquid 3 such as 5% human serum albumin solution in an amount of, for example, above 4 ⁇ 10 7 cells/ml.
- the booster is mixed with a medicament to give a pharmaceutical liquid composition.
- the pharmaceutical liquid composition is directly administered to the diseased part with an appropriate device, for example, with a drug administration device 4 as shown in FIG. 2 .
- the drug administration device 4 comprises a base tube 5 to which the pharmaceutical liquid composition is supplied, and an end tube 6 which is to be inserted into the tissue of the biobody and through which the pharmaceutical liquid composition is poured or injected into the disease part.
- the end tube 6 is provided with an ultrasonic element 7 (e.g. a cylindrical ceramic oscillator, etc.).
- the ultrasonic element 7 is supplied by an ultrasonic signal of 20 KHz to several MHz from an ultrasonic oscillation circuit 8 via a conductor 9 a , connectors 10 a and 10 b provided on the side of the base tube 5 , a part of the base tube 5 and a conductor 9 b provided within the end tube 6 .
- the application or injection of a medicament is carried out in the form of a pharmaceutical liquid composition which is prepared by previously mixing the medicament with the booster comprising a plurality of microbubbles of a gas in a liquid, wherein the medicament and the booster are mixed in a ration of 1:100 to 100:1 by weight.
- the pharmaceutical liquid composition is poured into the base tube 5 from the supply opening 11 provided on the tip of the base tube 5 , passes through a flow path 12 within the base tube 5 and a flow path 13 within the end tube 6 and is then administered to the diseased part or the portion close thereto of the patient via a pouring opening 14 provided at the bottom of the end tube 6 .
- an ultrasonic energy generated from an ultrasonic element 7 is applied to the liquid composition, by which cavitation occurs due to the ultrasonic energy.
- Microbubbles are formed at the occurrence of cavitation and when the microbubbles are decomposed, energy is generated, by which diffusion and penetration of the medicament is promoted. Since the pharmaceutical liquid composition contains a plurality of microbubbles of a gas, the microbubbles act as a nucleus for the cavitation by which the cavitation occurs more easily, in other words, the threshold value of occurrence of cavitation lowers. Accordingly, it is possible to generate the cavitation with less energy than the case of using no booster.
- the cavitation occurs generally at a lower threshold value of energy, but it has been found that the cavitation occurs most easily where the liquid contains microbubbles of a gas having a diameter of 0.1 to 100 ⁇ m.
- the drug administration device 4 as shown in FIG. 2 can be used, for example, for administering a pharmaceutical liquid composition into a blood vessel.
- a pharmaceutical liquid composition comprising a booster of the invention and a urokinase is injected into the part of thrombosis or the close portion thereof with the drug administration device 4 where the tip of the end tube 6 is inserted into the portion close to the thrombosis with applying ultrasound, by which the thrombolytic effects of the medicament are significantly increased and further the blood flow is recovered within a shorter period of time in comparison with the administration of the medicament without the booster.
- the drug administration device 4 may also be used for the removing hematoma in bleeding of brain.
- a pharmaceutical liquid composition comprising a booster of the invention and a thrombolytic agent (e.g. urokinase) is administered to the portion of hematoma with the drug administration device 4 with applying ultrasound like the above, by which the hematoma is easily lysed.
- a thrombolytic agent e.g. urokinase
- the pharmaceutical liquid composition can be administered transdermally with a drug administration device 15 as shown in FIG. 3 .
- a layer of a medicament 17 is provided below an ultrasonic element 16 (e.g. a disc shaped ceramic oscillator, etc.), under which an adhesive layer 18 having a medicament permeability is laminated, the whole of which is covered with a plastic cover 19 .
- the ultrasonic element 16 is supplied by ultrasonic signal from an ultrasonic oscillation circuit provided outside via a connector 20 , as shown in the drug administration device 4 in FIG. 2 .
- a pharmaceutical liquid composition comprising a mixture of a booster and a medicament is contained in the layer of a medicament 17 .
- this device 15 is adhered onto the skin with facing the adhesive layer 18 to the skin, and then an ultrasonic signal is supplied to the ultrasonic element 16 , by which an ultrasonic vibration from the ultrasonic element 16 is given to both of the medicament layer 17 and the skin and thereby the medicament contained in the medicament layer 17 is passed through the skin and is penetrated into the tissue to be treated.
- microbubbles of a gas are contained in the medicament layer 17 , cavitation occurs easily within the medicament layer 17 by application of ultrasound, and hence even when lower energy of the ultrasonic vibration is supplied from the ultrasonic element 16 , the diffusion and penetration of the medicament can effectively be done to result in rapid absorption of the medicament.
- the booster of the invention may also be used alone without mixing with a medicament in the therapy with ultrasound.
- a booster comprising a plurality of microbubbles of a gas in a liquid of the invention is previously injected into the blood vessel or to the portion close to the diseased part before application of ultrasound, by which the effect of heating with ultrasound is enhanced and thereby the therapeutic effects are significantly improved.
- cavitation occurs also by the ultrasonic vibration more easily because of using a liquid containing microbubbles of a gas, and hence, even by less energy of the ultrasonic vibration supplied from the ultrasonic element, the ultrasonic energy sufficient to the therapy is obtained and thereby the undesirable burns and unnecessary heating at other portions can L be avoided.
- chemotherapeutic agent suitable for the treatment of the tumors, by which the effects of the chemotherapeutic agent are more enhanced, where the diffusion and penetration of the medicament are improved owing to the booster.
- the substance such as human serum albumin in the booster of the invention is easily metabolized within the biobody and excreted outside the biobody, and hence, it is not harmful to human body. Besides, the amount of gas trapped within the microbubbles is extremely small and is easily dissolved in the blood fluid. Accordingly, the booster of the invention has no problem in the safety thereof.
- a 5% human serum albumin (8 ml) in a 10 ml-volume syringe is exposed to ultrasound with a sonicator (frequency, 20 KHz) by which vibration is given to the human serum albumin and a plurality of microbubbles of air are formed in the human serum albumin to give a booster comprising a human serum albumin containing a plurality of microbubbles of air.
- the 5% human serum albumin containing a plurality of microbubbles of air prepared in Example 1 is mixed with urokinase (concentration 1200 IU/ml) to give the desired pharmaceutical liquid composition.
- An artificial thrombosis was formed by Chandler's method. Blood (1 ml) that was collected from healthy humans (two persons) was entered into a flexible tube (inside diameter 3 mm, length 265 mm) and thereto was added calcium chloride, and then the tube was made a loop like shape, which was rotated at 12 rpm for 20 minutes to give an artificial thrombosis model.
- a ceramic ultrasonic element (width 2 mm, length 5 mm, thickness 1 mm) was inserted into the tip of a catheter (diameter 2 mm), and an oscillating element was connected to an oscillator provided outside with a fine connector passed through the catheter.
- a fine tube for pouring a test solution was provided at an opening opposite to the opening of the catheter end.
- the artificial thrombosis prepared above was added to a test tube together with blood, and the ultrasonic catheter was inserted into the test tube so that the end of the catheter was set close to the portion of the artificial thrombosis (at a distance of about 5 mm), and to the test tube a mixture of urokinase and a booster prepared in Example 1 was added at a rate of 1 ml per minute, wherein urokinase (concentration 1200 IU/ml) and the booster were mixed immediately before pouring at a mixing ration of 1:1 by weight. The mixture was refluxed while keeping the volume of the test solution at a constant level by removing excess volume of the solution by suction.
- the ultrasound (170 KHz) was exposed to the mixture by a pulse method (exposed for 2 seconds and stopped for 4 seconds) for 2 minutes (total exposing time 40 seconds). After the exposure, the ultrasonic catheter was removed from the test tube, and the mixture was incubated at 37 degrees C. for 5 to 120 minutes, washed with a physiological saline solution several times and dried overnight. Thereafter, the dried mixture was weighed. As a control, the above was repeated by using only a physiological saline solution.
- the rate of fibrinolysis was calculated by the following equation:
- Fibrinolysis ⁇ ⁇ rate ⁇ ( % ) [ ⁇ Weight ⁇ ⁇ of ⁇ thrombosis ⁇ ⁇ in ⁇ ⁇ control ⁇ ] - [ ⁇ Weight ⁇ ⁇ of thrombosis ⁇ ⁇ treated ] Weight ⁇ ⁇ of ⁇ ⁇ thrombosis ⁇ ⁇ in ⁇ ⁇ control ⁇ 100
- FIG. 4 shows the results in the thrombosis prepared by using blood collected from one person, wherein the symbol — ⁇ — is the data obtained in the addition of urokinase alone without exposure of ultrasound, — ⁇ — is the data obtained in the addition of urokinase alone with exposure of ultrasound, and — ⁇ — is the data obtained in the addition of a mixture of urokinase and the booster with exposure of ultrasound.
- the time for achieving 20% fibrinolysis was 45 minutes by urokinase alone without exposure of ultrasound, 30 minutes by a combination of urokinase and exposure of ultrasound, and only 10 minutes by a combination of a mixture of urokinase and a booster and exposure of ultrasound.
- the fibrinolytic effects of urokinase were significantly enhanced by using a booster with application of ultrasound.
- FIG. 5 shows the results in the thrombosis prepared by using blood collected from another person and with reduced energy of ultrasound by 15%, wherein the symbols are the same as in FIG. 4 .
- the fibrinolytic effects were significantly enhanced by using a mixture of urokinase and the booster. That is, in case of using urokinase alone with exposure of ultrasound, the 50% fibrinolysis was achieved by the treatment for 60 minutes, but in case of using a mixture of urokinase and the booster with exposure of ultrasound, it reduced to one fourth, i.e. it was achieved by the treatment only for 15 minutes.
Abstract
A booster comprising a plurality of microbubbles of a gas in a liquid, e.g. about 4×107 cells/ml of microbubbles of a gas having a diameter of 0.1 to 100 μm in a 3 to 5% human serum albumin solution, and a pharmaceutical liquid composition comprising the booster as set forth above and a medicament, which are useful for the therapy of various diseases together with exposure of ultrasonic, where the therapeutic effects of the medicament is enhanced by the application of ultrasound in the presence of the booster.
Description
- This application is a continuation of application Ser. No. 10/400,337, filed Mar. 26, 2003, which is a continuation of application Ser. No. 09/375,339, filed Aug. 16, 1999, now U.S. Pat. No. 6,585,678, which is a divisional of application Ser. No. 08/652,690, filed May 30, 1996, now U.S. Pat. No. RE36,939, which is a reissue of U.S. Pat. No. 5,315,998, filed Mar. 20, 1992. This application also claims priority under §119 to Japanese Application No. 3-058970, filed Mar. 22, 1991. Each of the above-referenced related applications is incorporated herein by reference in its entirety
- This invention relates to a booster useful for enhancing the effects of ultrasound in the therapy of various diseases and a pharmaceutical liquid composition containing the booster and a medicament which shows enhanced diffusion and penetration of the medicament into the body by applying ultrasound. More particularly, it relates to a booster useful for therapy of various disease by applying ultrasound which comprises a plurality of microbubbles of a gas in a liquid, a pharmaceutical liquid composition comprising a plurality of microbubbles of a gas and a medicament in a liquid, and the use thereof in the therapy of various diseases while applying ultrasound.
- It is known that various diseases are remedied by the aid of ultrasonic vibration. For example, it is described in Japanese Patent First Publication (Kokai) No. 115591/1977, etc. that percutaneous absorption of a medicament is enhanced by applying an ultrasonic vibration. Japanese Patent First Publication (Kokai) No. 180275/1990 discloses a drug-injecting device which is effective on the diffusion and penetration of the drug by applying an ultrasonic vibration in the step of injecting a drug into a human body via a catheter or a drug-injecting tube. U.S. Pat. Nos. 4,953,565 and 5,007,438 also disclose the technique of percutaneous absorption of medicaments by the aid of ultrasonic vibration. It is also reported that a tumor can be remedied by concentratedly applying ultrasound from outside the body.
- In order to enhance the therapeutic effects with ultrasound, it is required to apply a high energy ultrasonic vibration. However, ultrasonic vibration at an energy that is too high causes disadvantageously bums or unnecessary heat at the portion other than the desired portion. On the other hand, when the energy of an ultrasonic vibration is lowered for eliminating such disadvantages, there is a problem of less effect of the ultrasound at the desired portion.
- The present inventors have intensively studied enhancing the effects of ultrasound at a lower energy of an ultrasonic vibration and have found that a booster comprising a plurality of microbubbles of a gas in a liquid is useful for the desired enhancement of the effects of ultrasound.
- An object of the invention is to provide a booster useful for enhancing the effects of ultrasound which comprises a plurality of microbubbles of a gas in a liquid. Another object of the invention is to provide a pharmaceutical liquid composition containing the booster and a medicament which is useful for the therapy of various diseases together with the application of ultrasound. A further object of the invention is to provide a method for enhancing the effects by the application of ultrasound in the therapy of various diseases which comprises injecting the booster or the pharmaceutical liquid composition as set forth above into the portion to be remedied while applying ultrasound thereto. These and other objects and advantages of the invention will be apparent to those skilled in the art from the following description.
-
FIG. 1 shows a schematic view of one of the microbubbles contained in the booster of the invention. -
FIG. 2 shows a schematic sectional view of one embodiment of a drug administration device used for injecting, pouring, applying or circulating the booster or the pharmaceutical liquid composition of the invention. -
FIG. 3 shows a schematic sectional view of one embodiment of a drug administration device used for transdermal administration of the booster or the pharmaceutical liquid composition of the invention. -
FIG. 4 andFIG. 5 show graphs showing fibrinolysis by application of ultrasound with or without the booster of the invention. - The booster of the invention comprises a liquid containing a plurality of microbubbles of a gas having a diameter of 0.1 to 100 μm. The microbubbles are formed by entrapping microspheres of a gas into a liquid. The booster contains, for example, about 4×107 of the microbubbles per one milliliter of a liquid. The microbubbles are made of various gases such as air, oxygen gas, carbon dioxide gas, inert gases (e.g. xenon, krypton, argon, neon, helium, etc.), preferably air and oxygen gas. The liquid includes any liquid which can form microbubbles, for example, human serum albumin (e.g. 3 to 5% human serum albumin), a physiological saline solution, a 5% aqueous glucose solution, an aqueous indocyanine green solution, autoblood, an aqueous solution of maglumine diatriazoate (=renografin), and any other X-ray contrast medium.
- The booster can be prepared by a known method, for example, by agitating the liquid as mentioned above while blowing a gas as mentioned above into the liquid, or alternatively exposing the liquid to ultrasound with a sonicator under a gaseous atmosphere, whereby a vibration is applied to the liquid to form microbubbles of the gas.
- The pharmaceutical liquid composition of the invention comprises a plurality of microbubbles of a gas and a medicament in a liquid. The microbubbles of a gas and liquid are the same as mentioned above. The medicament includes any known medicaments effective for the desired therapy which can be absorbed percutaneously, for example, anti-thrombosis agents (e.g. urokinase, tissue plasminogen activator, etc.), hormones (e.g. insulin, etc.), theophylline, lidocaine, antibiotics, antineoplastic agents which are sensitive to ultrasound (e.g. doxorubicin (=adriamycin), cytarabine (=Ara.C), etc.), and the like. The medicament can be contained in a therapeutically effective amount as usually used. The pharmaceutical liquid composition can be prepared by mixing a medicament with a booster comprising a plurality of microbubbles of a gas in a liquid. The mixing ratio may vary depending on the desired amount and kind of the medicament and the kind of the liquid, but is usually in a range of 1:100 to 100:1 by weight (a medicament/a booster).
- According to the invention, the therapeutic effect of ultrasound is boosted by the presence of a booster of the invention. Particularly, when a pharmaceutical liquid composition containing the booster and a medicament is poured or injected into a body in parenteral routes, such as intravenously, percutaneously or intramuscularly, while applying thereto an ultrasonic vibration, the therapeutic effects of the medicament is significantly enhanced. When an ultrasound from an ultrasonic element is applied to the liquid containing the booster and medicament, cavitation occurs in the liquid composition, and the medicament is diffused and penetrated into the desired portion of the biobody by the aid of vibration induced by the cavitation. The cavitation occurs when the level of vibration energy exceeds a certain threshold value. When the ultrasound is applied to the liquid composition of the invention, the threshold value of the vibration energy is reduced due to the presence of a plurality of microbubbles of a gas. That is, the microbubbles of a gas act as nucleus of cavitation and thereby the cavitation occurs more easily. Therefore, according to the invention, the desired ultrasonic energy necessary for the desired diffusion and penetration of a medicament is reduced.
- The desired ultrasound is applied by conventional ultrasonic devices which can supply an ultrasonic signal of 20 KHz to several MHz.
- With reference to the accompanying drawings, the invention is illustrated in more detail.
-
FIG. 1 shows a schematic view of one of the plurality of microbubbles of a gas contained in the booster of the invention, wherein the microbubble of a gas has a diameter of 0.1 to 100 μm and is composed of a shell of human serum albumin 1 andgas 2 entrapped within the microbubble. The microbubbles are contained in aliquid 3 such as 5% human serum albumin solution in an amount of, for example, above 4×107 cells/ml. - The booster is mixed with a medicament to give a pharmaceutical liquid composition. The pharmaceutical liquid composition is directly administered to the diseased part with an appropriate device, for example, with a
drug administration device 4 as shown inFIG. 2 . Thedrug administration device 4 comprises abase tube 5 to which the pharmaceutical liquid composition is supplied, and anend tube 6 which is to be inserted into the tissue of the biobody and through which the pharmaceutical liquid composition is poured or injected into the disease part. Theend tube 6 is provided with an ultrasonic element 7 (e.g. a cylindrical ceramic oscillator, etc.). Theultrasonic element 7 is supplied by an ultrasonic signal of 20 KHz to several MHz from anultrasonic oscillation circuit 8 via aconductor 9 a, connectors 10 a and 10 b provided on the side of thebase tube 5, a part of thebase tube 5 and aconductor 9 b provided within theend tube 6. - The application or injection of a medicament is carried out in the form of a pharmaceutical liquid composition which is prepared by previously mixing the medicament with the booster comprising a plurality of microbubbles of a gas in a liquid, wherein the medicament and the booster are mixed in a ration of 1:100 to 100:1 by weight. The pharmaceutical liquid composition is poured into the
base tube 5 from the supply opening 11 provided on the tip of thebase tube 5, passes through aflow path 12 within thebase tube 5 and aflow path 13 within theend tube 6 and is then administered to the diseased part or the portion close thereto of the patient via a pouringopening 14 provided at the bottom of theend tube 6. - When the pharmaceutical liquid composition is administered into the diseased part or the portion close thereto through the pouring
opening 14, an ultrasonic energy generated from anultrasonic element 7 is applied to the liquid composition, by which cavitation occurs due to the ultrasonic energy. Microbubbles are formed at the occurrence of cavitation and when the microbubbles are decomposed, energy is generated, by which diffusion and penetration of the medicament is promoted. Since the pharmaceutical liquid composition contains a plurality of microbubbles of a gas, the microbubbles act as a nucleus for the cavitation by which the cavitation occurs more easily, in other words, the threshold value of occurrence of cavitation lowers. Accordingly, it is possible to generate the cavitation with less energy than the case of using no booster. - When an ultrasonic vibration is applied to a liquid, if the liquid contains any material being able to become a nucleus, the cavitation occurs generally at a lower threshold value of energy, but it has been found that the cavitation occurs most easily where the liquid contains microbubbles of a gas having a diameter of 0.1 to 100 μm.
- The
drug administration device 4 as shown inFIG. 2 can be used, for example, for administering a pharmaceutical liquid composition into a blood vessel. For instance, in the treatment of coronary thrombosis, a pharmaceutical liquid composition comprising a booster of the invention and a urokinase is injected into the part of thrombosis or the close portion thereof with thedrug administration device 4 where the tip of theend tube 6 is inserted into the portion close to the thrombosis with applying ultrasound, by which the thrombolytic effects of the medicament are significantly increased and further the blood flow is recovered within a shorter period of time in comparison with the administration of the medicament without the booster. Thedrug administration device 4 may also be used for the removing hematoma in bleeding of brain. For example, a pharmaceutical liquid composition comprising a booster of the invention and a thrombolytic agent (e.g. urokinase) is administered to the portion of hematoma with thedrug administration device 4 with applying ultrasound like the above, by which the hematoma is easily lysed. - In another embodiment of the invention, the pharmaceutical liquid composition can be administered transdermally with a
drug administration device 15 as shown inFIG. 3 . - In the
drug administration device 15 suitable for transdermal administration of a medicament, a layer of amedicament 17 is provided below an ultrasonic element 16 (e.g. a disc shaped ceramic oscillator, etc.), under which anadhesive layer 18 having a medicament permeability is laminated, the whole of which is covered with aplastic cover 19. Theultrasonic element 16 is supplied by ultrasonic signal from an ultrasonic oscillation circuit provided outside via aconnector 20, as shown in thedrug administration device 4 inFIG. 2 . - In the
device 15 ofFIG. 3 , a pharmaceutical liquid composition comprising a mixture of a booster and a medicament is contained in the layer of amedicament 17. When thisdevice 15 is used, it is adhered onto the skin with facing theadhesive layer 18 to the skin, and then an ultrasonic signal is supplied to theultrasonic element 16, by which an ultrasonic vibration from theultrasonic element 16 is given to both of themedicament layer 17 and the skin and thereby the medicament contained in themedicament layer 17 is passed through the skin and is penetrated into the tissue to be treated. In this embodiment, since microbubbles of a gas are contained in themedicament layer 17, cavitation occurs easily within themedicament layer 17 by application of ultrasound, and hence even when lower energy of the ultrasonic vibration is supplied from theultrasonic element 16, the diffusion and penetration of the medicament can effectively be done to result in rapid absorption of the medicament. - The booster of the invention may also be used alone without mixing with a medicament in the therapy with ultrasound. For example, in the therapy of tumors by heating the diseased part of the tissue with ultrasound, that is, by concentratedly applying an ultrasonic vibration outside the biobody, a booster comprising a plurality of microbubbles of a gas in a liquid of the invention is previously injected into the blood vessel or to the portion close to the diseased part before application of ultrasound, by which the effect of heating with ultrasound is enhanced and thereby the therapeutic effects are significantly improved. In this embodiment, cavitation occurs also by the ultrasonic vibration more easily because of using a liquid containing microbubbles of a gas, and hence, even by less energy of the ultrasonic vibration supplied from the ultrasonic element, the ultrasonic energy sufficient to the therapy is obtained and thereby the undesirable burns and unnecessary heating at other portions can L be avoided.
- In the treatment of tumors, it is, of course, more effective to use it together with a chemotherapeutic agent suitable for the treatment of the tumors, by which the effects of the chemotherapeutic agent are more enhanced, where the diffusion and penetration of the medicament are improved owing to the booster.
- The substance such as human serum albumin in the booster of the invention is easily metabolized within the biobody and excreted outside the biobody, and hence, it is not harmful to human body. Besides, the amount of gas trapped within the microbubbles is extremely small and is easily dissolved in the blood fluid. Accordingly, the booster of the invention has no problem in the safety thereof.
- The preparation of the booster and pharmaceutical liquid composition of the invention and effects thereof are illustrated by the following Examples and Experiment, but it should not be construed to be limited thereto.
- A 5% human serum albumin (8 ml) in a 10 ml-volume syringe is exposed to ultrasound with a sonicator (frequency, 20 KHz) by which vibration is given to the human serum albumin and a plurality of microbubbles of air are formed in the human serum albumin to give a booster comprising a human serum albumin containing a plurality of microbubbles of air.
- The 5% human serum albumin containing a plurality of microbubbles of air prepared in Example 1 is mixed with urokinase (concentration 1200 IU/ml) to give the desired pharmaceutical liquid composition.
- An artificial thrombosis was formed by Chandler's method. Blood (1 ml) that was collected from healthy humans (two persons) was entered into a flexible tube (inside
diameter 3 mm, length 265 mm) and thereto was added calcium chloride, and then the tube was made a loop like shape, which was rotated at 12 rpm for 20 minutes to give an artificial thrombosis model. - A ceramic ultrasonic element (
width 2 mm,length 5 mm, thickness 1 mm) was inserted into the tip of a catheter (diameter 2 mm), and an oscillating element was connected to an oscillator provided outside with a fine connector passed through the catheter. A fine tube for pouring a test solution was provided at an opening opposite to the opening of the catheter end. - The artificial thrombosis prepared above was added to a test tube together with blood, and the ultrasonic catheter was inserted into the test tube so that the end of the catheter was set close to the portion of the artificial thrombosis (at a distance of about 5 mm), and to the test tube a mixture of urokinase and a booster prepared in Example 1 was added at a rate of 1 ml per minute, wherein urokinase (concentration 1200 IU/ml) and the booster were mixed immediately before pouring at a mixing ration of 1:1 by weight. The mixture was refluxed while keeping the volume of the test solution at a constant level by removing excess volume of the solution by suction. The ultrasound (170 KHz) was exposed to the mixture by a pulse method (exposed for 2 seconds and stopped for 4 seconds) for 2 minutes (total exposing
time 40 seconds). After the exposure, the ultrasonic catheter was removed from the test tube, and the mixture was incubated at 37 degrees C. for 5 to 120 minutes, washed with a physiological saline solution several times and dried overnight. Thereafter, the dried mixture was weighed. As a control, the above was repeated by using only a physiological saline solution. - The rate of fibrinolysis was calculated by the following equation:
-
- The results are shown in the accompanying
FIGS. 4 and 5 wherein there are shown in average of twice tests. -
FIG. 4 shows the results in the thrombosis prepared by using blood collected from one person, wherein the symbol —□— is the data obtained in the addition of urokinase alone without exposure of ultrasound, —♦— is the data obtained in the addition of urokinase alone with exposure of ultrasound, and —▪— is the data obtained in the addition of a mixture of urokinase and the booster with exposure of ultrasound. - As shown in
FIG. 4 , the time for achieving 20% fibrinolysis was 45 minutes by urokinase alone without exposure of ultrasound, 30 minutes by a combination of urokinase and exposure of ultrasound, and only 10 minutes by a combination of a mixture of urokinase and a booster and exposure of ultrasound. The fibrinolytic effects of urokinase (both the rate of fibrinolysis and the fibrinolytic time) were significantly enhanced by using a booster with application of ultrasound. -
FIG. 5 shows the results in the thrombosis prepared by using blood collected from another person and with reduced energy of ultrasound by 15%, wherein the symbols are the same as inFIG. 4 . As shown inFIG. 5 , the fibrinolytic effects were significantly enhanced by using a mixture of urokinase and the booster. That is, in case of using urokinase alone with exposure of ultrasound, the 50% fibrinolysis was achieved by the treatment for 60 minutes, but in case of using a mixture of urokinase and the booster with exposure of ultrasound, it reduced to one fourth, i.e. it was achieved by the treatment only for 15 minutes.
Claims (18)
1. A method of enhancing the effects of ultrasound energy at a treatment site, comprising:
advancing a distal end portion of an elongate tube toward the treatment site;
delivering a pharmaceutical liquid composition through a lumen of said elongate tube; and
emitting ultrasound energy at a frequency between about 20 KHz to about several MHz into said pharmaceutical liquid composition to promote diffusion of said medicament at the treatment site.
2. The method of claim 1 wherein said pharmaceutical liquid composition comprises a medicament.
3. The method of claim 2 wherein said medicament comprises a hormone.
4. The method of claim 2 wherein said medicament comprises an antibiotic.
5. The method of claim 2 wherein said medicament comprises a chemotherapeutic agent.
6. The method of claim 2 wherein said medicament comprises an antineoplastic agent.
7. The method of claim 6 wherein said antineoplastic agent is doxorubicin.
8. The method of claim 6 wherein said antineoplastic agent is cytarabine.
9. The method of claim 2 wherein said medicament comprises an antithrombotic agent.
10. The method of claim 2 wherein said medicament comprises a thrombolytic agent.
11. The method of claim 10 wherein said thrombolytic agent comprises urokinase.
12. The method of claim 10 wherein said thrombolytic agent comprises tissue plasminogen activator.
13. The method of claim 1 , wherein the ultrasound energy is emitted from an ultrasonic element disposed along said distal end portion of said elongate tube.
14. A method of enhancing the effects of ultrasound energy at a treatment site, comprising:
advancing a distal end portion of an elongate tube toward the treatment site;
delivering a pharmaceutical liquid composition through a lumen of said elongate tube;
emitting ultrasound energy at a frequency between about 20 KHz to about several MHz into said pharmaceutical liquid composition to promote diffusion of said medicament at the treatment site; and
generating cavitation at the treatment site.
15. The method of claim 14 wherein said pharmaceutical liquid composition comprises a medicament.
16. The method of claim 15 wherein said medicament comprises a thrombolytic agent.
17. The method of claim 16 wherein said thrombolytic agent comprises urokinase.
18. The method of claim 16 wherein said thrombolytic agent comprises tissue plasminogen activator.
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US07/855,545 US5315998A (en) | 1991-03-22 | 1992-03-20 | Booster for therapy of diseases with ultrasound and pharmaceutical liquid composition containing the same |
US08/652,690 USRE36939E (en) | 1991-03-22 | 1996-05-30 | Composition for therapy of diseases with ultrasonic and pharmaceutical liquid composition containing the same |
US09/375,339 US6585678B1 (en) | 1991-03-22 | 1999-08-16 | Booster for therapy of disease with ultrasound and pharmaceutical IDLIQU composition containing the same |
US10/400,337 US20030191446A1 (en) | 1991-03-22 | 2003-03-26 | Booster for therapy of diseases with ultrasound and pharmaceutical liquid composition containing the same |
US12/172,686 US20080274097A1 (en) | 1991-03-22 | 2008-07-14 | Booster for therapy of diseases with ultrasound and pharmaceutical liquid composition containing the same |
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US10/400,337 Abandoned US20030191446A1 (en) | 1991-03-22 | 2003-03-26 | Booster for therapy of diseases with ultrasound and pharmaceutical liquid composition containing the same |
US12/172,686 Abandoned US20080274097A1 (en) | 1991-03-22 | 2008-07-14 | Booster for therapy of diseases with ultrasound and pharmaceutical liquid composition containing the same |
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US09/375,339 Expired - Fee Related US6585678B1 (en) | 1991-03-22 | 1999-08-16 | Booster for therapy of disease with ultrasound and pharmaceutical IDLIQU composition containing the same |
US10/400,337 Abandoned US20030191446A1 (en) | 1991-03-22 | 2003-03-26 | Booster for therapy of diseases with ultrasound and pharmaceutical liquid composition containing the same |
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Cited By (5)
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Families Citing this family (210)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5542935A (en) | 1989-12-22 | 1996-08-06 | Imarx Pharmaceutical Corp. | Therapeutic delivery systems related applications |
US6001335A (en) | 1989-12-22 | 1999-12-14 | Imarx Pharmaceutical Corp. | Contrasting agents for ultrasonic imaging and methods for preparing the same |
US5585112A (en) | 1989-12-22 | 1996-12-17 | Imarx Pharmaceutical Corp. | Method of preparing gas and gaseous precursor-filled microspheres |
US5776429A (en) | 1989-12-22 | 1998-07-07 | Imarx Pharmaceutical Corp. | Method of preparing gas-filled microspheres using a lyophilized lipids |
US6551576B1 (en) | 1989-12-22 | 2003-04-22 | Bristol-Myers Squibb Medical Imaging, Inc. | Container with multi-phase composition for use in diagnostic and therapeutic applications |
US5656211A (en) | 1989-12-22 | 1997-08-12 | Imarx Pharmaceutical Corp. | Apparatus and method for making gas-filled vesicles of optimal size |
US5469854A (en) | 1989-12-22 | 1995-11-28 | Imarx Pharmaceutical Corp. | Methods of preparing gas-filled liposomes |
US5580575A (en) | 1989-12-22 | 1996-12-03 | Imarx Pharmaceutical Corp. | Therapeutic drug delivery systems |
US6146657A (en) | 1989-12-22 | 2000-11-14 | Imarx Pharmaceutical Corp. | Gas-filled lipid spheres for use in diagnostic and therapeutic applications |
US6088613A (en) | 1989-12-22 | 2000-07-11 | Imarx Pharmaceutical Corp. | Method of magnetic resonance focused surgical and therapeutic ultrasound |
US5305757A (en) | 1989-12-22 | 1994-04-26 | Unger Evan C | Gas filled liposomes and their use as ultrasonic contrast agents |
US5922304A (en) | 1989-12-22 | 1999-07-13 | Imarx Pharmaceutical Corp. | Gaseous precursor filled microspheres as magnetic resonance imaging contrast agents |
DE69215722T3 (en) * | 1991-03-22 | 2001-03-08 | Katsuro Tachibana | Amplifiers for ultrasound therapy of diseases and liquid pharmaceutical compositions containing them |
US5874062A (en) | 1991-04-05 | 1999-02-23 | Imarx Pharmaceutical Corp. | Methods of computed tomography using perfluorocarbon gaseous filled microspheres as contrast agents |
US5205290A (en) | 1991-04-05 | 1993-04-27 | Unger Evan C | Low density microspheres and their use as contrast agents for computed tomography |
US5713848A (en) * | 1993-05-19 | 1998-02-03 | Dubrul; Will R. | Vibrating catheter |
US5701899A (en) * | 1993-05-12 | 1997-12-30 | The Board Of Regents Of The University Of Nebraska | Perfluorobutane ultrasound contrast agent and methods for its manufacture and use |
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AU7655194A (en) * | 1993-09-09 | 1995-03-27 | Schering Aktiengesellschaft | Active principles and gas containing microparticles |
DE4330958A1 (en) * | 1993-09-09 | 1995-03-16 | Schering Ag | Novel microparticles containing active compound, media containing these, their use for the ultrasonically controlled release of active compounds and process for the production thereof |
US5814599A (en) * | 1995-08-04 | 1998-09-29 | Massachusetts Insitiute Of Technology | Transdermal delivery of encapsulated drugs |
US5540909A (en) * | 1994-09-28 | 1996-07-30 | Alliance Pharmaceutical Corp. | Harmonic ultrasound imaging with microbubbles |
US6743779B1 (en) | 1994-11-29 | 2004-06-01 | Imarx Pharmaceutical Corp. | Methods for delivering compounds into a cell |
AU1426995A (en) * | 1995-01-19 | 1996-08-07 | Ten Cate, F.J. | Local delivery and monitoring of drugs |
US5830430A (en) | 1995-02-21 | 1998-11-03 | Imarx Pharmaceutical Corp. | Cationic lipids and the use thereof |
US6176842B1 (en) * | 1995-03-08 | 2001-01-23 | Ekos Corporation | Ultrasound assembly for use with light activated drugs |
US6210356B1 (en) * | 1998-08-05 | 2001-04-03 | Ekos Corporation | Ultrasound assembly for use with a catheter |
US5997898A (en) | 1995-06-06 | 1999-12-07 | Imarx Pharmaceutical Corp. | Stabilized compositions of fluorinated amphiphiles for methods of therapeutic delivery |
US6033645A (en) | 1996-06-19 | 2000-03-07 | Unger; Evan C. | Methods for diagnostic imaging by regulating the administration rate of a contrast agent |
US6521211B1 (en) | 1995-06-07 | 2003-02-18 | Bristol-Myers Squibb Medical Imaging, Inc. | Methods of imaging and treatment with targeted compositions |
US6231834B1 (en) | 1995-06-07 | 2001-05-15 | Imarx Pharmaceutical Corp. | Methods for ultrasound imaging involving the use of a contrast agent and multiple images and processing of same |
US5804162A (en) * | 1995-06-07 | 1998-09-08 | Alliance Pharmaceutical Corp. | Gas emulsions stabilized with fluorinated ethers having low Ostwald coefficients |
US6139819A (en) | 1995-06-07 | 2000-10-31 | Imarx Pharmaceutical Corp. | Targeted contrast agents for diagnostic and therapeutic use |
US5947921A (en) * | 1995-12-18 | 1999-09-07 | Massachusetts Institute Of Technology | Chemical and physical enhancers and ultrasound for transdermal drug delivery |
US6041253A (en) * | 1995-12-18 | 2000-03-21 | Massachusetts Institute Of Technology | Effect of electric field and ultrasound for transdermal drug delivery |
US6002961A (en) * | 1995-07-25 | 1999-12-14 | Massachusetts Institute Of Technology | Transdermal protein delivery using low-frequency sonophoresis |
US5648098A (en) * | 1995-10-17 | 1997-07-15 | The Board Of Regents Of The University Of Nebraska | Thrombolytic agents and methods of treatment for thrombosis |
US5728062A (en) * | 1995-11-30 | 1998-03-17 | Pharmasonics, Inc. | Apparatus and methods for vibratory intraluminal therapy employing magnetostrictive transducers |
US5735811A (en) * | 1995-11-30 | 1998-04-07 | Pharmasonics, Inc. | Apparatus and methods for ultrasonically enhanced fluid delivery |
US5725494A (en) | 1995-11-30 | 1998-03-10 | Pharmasonics, Inc. | Apparatus and methods for ultrasonically enhanced intraluminal therapy |
AU721034B2 (en) * | 1996-02-15 | 2000-06-22 | Biosense, Inc. | Catheter based surgery |
US6245747B1 (en) | 1996-03-12 | 2001-06-12 | The Board Of Regents Of The University Of Nebraska | Targeted site specific antisense oligodeoxynucleotide delivery method |
WO1997033474A1 (en) * | 1996-03-12 | 1997-09-18 | Board Of Regents Of The University Of Nebraska | Targeted site specific drug delivery compositions and method of use |
JP2001507207A (en) | 1996-05-01 | 2001-06-05 | イマアーレクス・フアーマシユーチカル・コーポレーシヨン | Methods for delivering compounds to cells |
US5849727A (en) * | 1996-06-28 | 1998-12-15 | Board Of Regents Of The University Of Nebraska | Compositions and methods for altering the biodistribution of biological agents |
JP2002515786A (en) | 1996-06-28 | 2002-05-28 | ソントラ メディカル,エル.ピー. | Ultrasound enhancement of transdermal delivery |
BE1010407A4 (en) * | 1996-07-04 | 1998-07-07 | Undatim Ultrasonics | Method and installation of water treatment. |
US6414139B1 (en) | 1996-09-03 | 2002-07-02 | Imarx Therapeutics, Inc. | Silicon amphiphilic compounds and the use thereof |
US6464660B2 (en) | 1996-09-05 | 2002-10-15 | Pharmasonics, Inc. | Balloon catheters having ultrasonically driven interface surfaces and methods for their use |
US5846218A (en) | 1996-09-05 | 1998-12-08 | Pharmasonics, Inc. | Balloon catheters having ultrasonically driven interface surfaces and methods for their use |
US5846517A (en) | 1996-09-11 | 1998-12-08 | Imarx Pharmaceutical Corp. | Methods for diagnostic imaging using a renal contrast agent and a vasodilator |
CA2263568C (en) | 1996-09-11 | 2008-12-02 | Imarx Pharmaceutical Corp. | Methods for diagnostic imaging using a contrast agent and a renal vasodilator |
US6024717A (en) * | 1996-10-24 | 2000-02-15 | Vibrx, Inc. | Apparatus and method for sonically enhanced drug delivery |
US6221038B1 (en) | 1996-11-27 | 2001-04-24 | Pharmasonics, Inc. | Apparatus and methods for vibratory intraluminal therapy employing magnetostrictive transducers |
US6120751A (en) | 1997-03-21 | 2000-09-19 | Imarx Pharmaceutical Corp. | Charged lipids and uses for the same |
US6143276A (en) | 1997-03-21 | 2000-11-07 | Imarx Pharmaceutical Corp. | Methods for delivering bioactive agents to regions of elevated temperatures |
US6537246B1 (en) | 1997-06-18 | 2003-03-25 | Imarx Therapeutics, Inc. | Oxygen delivery agents and uses for the same |
US6090800A (en) | 1997-05-06 | 2000-07-18 | Imarx Pharmaceutical Corp. | Lipid soluble steroid prodrugs |
US6676626B1 (en) | 1998-05-01 | 2004-01-13 | Ekos Corporation | Ultrasound assembly with increased efficacy |
US6582392B1 (en) * | 1998-05-01 | 2003-06-24 | Ekos Corporation | Ultrasound assembly for use with a catheter |
US6723063B1 (en) | 1998-06-29 | 2004-04-20 | Ekos Corporation | Sheath for use with an ultrasound element |
US6416740B1 (en) | 1997-05-13 | 2002-07-09 | Bristol-Myers Squibb Medical Imaging, Inc. | Acoustically active drug delivery systems |
US5931805A (en) * | 1997-06-02 | 1999-08-03 | Pharmasonics, Inc. | Catheters comprising bending transducers and methods for their use |
US6228046B1 (en) | 1997-06-02 | 2001-05-08 | Pharmasonics, Inc. | Catheters comprising a plurality of oscillators and methods for their use |
US6548047B1 (en) | 1997-09-15 | 2003-04-15 | Bristol-Myers Squibb Medical Imaging, Inc. | Thermal preactivation of gaseous precursor filled compositions |
US6123923A (en) | 1997-12-18 | 2000-09-26 | Imarx Pharmaceutical Corp. | Optoacoustic contrast agents and methods for their use |
JP2001526926A (en) | 1997-12-31 | 2001-12-25 | ファーマソニックス,インコーポレイテッド | Methods and systems for suppressing vascular hyperplasia |
US8287483B2 (en) * | 1998-01-08 | 2012-10-16 | Echo Therapeutics, Inc. | Method and apparatus for enhancement of transdermal transport |
US7066884B2 (en) | 1998-01-08 | 2006-06-27 | Sontra Medical, Inc. | System, method, and device for non-invasive body fluid sampling and analysis |
US20060015058A1 (en) * | 1998-01-08 | 2006-01-19 | Kellogg Scott C | Agents and methods for enhancement of transdermal transport |
US7273458B2 (en) | 1998-01-12 | 2007-09-25 | Georgia Tech Research Corporation | Method of applying acoustic energy effective to alter transport or cell viability |
US20010003580A1 (en) | 1998-01-14 | 2001-06-14 | Poh K. Hui | Preparation of a lipid blend and a phospholipid suspension containing the lipid blend |
JPH11244283A (en) * | 1998-03-05 | 1999-09-14 | Ge Yokogawa Medical Systems Ltd | Ultrasonic image pickup method and its device |
US6135976A (en) * | 1998-09-25 | 2000-10-24 | Ekos Corporation | Method, device and kit for performing gene therapy |
US20040171980A1 (en) | 1998-12-18 | 2004-09-02 | Sontra Medical, Inc. | Method and apparatus for enhancement of transdermal transport |
US6387116B1 (en) | 1999-06-30 | 2002-05-14 | Pharmasonics, Inc. | Methods and kits for the inhibition of hyperplasia in vascular fistulas and grafts |
US6361554B1 (en) | 1999-06-30 | 2002-03-26 | Pharmasonics, Inc. | Methods and apparatus for the subcutaneous delivery of acoustic vibrations |
EP1202670A4 (en) * | 1999-08-13 | 2004-11-10 | Point Biomedical Corp | Hollow microspheres with controlled fragility for medical use |
US6944493B2 (en) * | 1999-09-10 | 2005-09-13 | Akora, Inc. | Indocyanine green (ICG) compositions and related methods of use |
US6351663B1 (en) | 1999-09-10 | 2002-02-26 | Akorn, Inc. | Methods for diagnosing and treating conditions associated with abnormal vasculature using fluorescent dye angiography and dye-enhanced photocoagulation |
US6439236B1 (en) | 1999-10-25 | 2002-08-27 | The Board Of Regents Of The University Of Nebraska | Methods for inducing atrial and ventricular rhythms using ultrasound and microbubbles |
US6443976B1 (en) | 1999-11-30 | 2002-09-03 | Akorn, Inc. | Methods for treating conditions and illnesses associated with abnormal vasculature |
US20040158317A1 (en) * | 2000-07-18 | 2004-08-12 | Pharmasonics, Inc. | Coated stent with ultrasound therapy |
US6514221B2 (en) * | 2000-07-27 | 2003-02-04 | Brigham And Women's Hospital, Inc. | Blood-brain barrier opening |
JP2005520574A (en) * | 2000-09-25 | 2005-07-14 | アドバンスト メディカル アプリケーションズ インコーポレーテッド | Ultrasound method and apparatus for wound treatment |
US6964647B1 (en) | 2000-10-06 | 2005-11-15 | Ellaz Babaev | Nozzle for ultrasound wound treatment |
US6601581B1 (en) | 2000-11-01 | 2003-08-05 | Advanced Medical Applications, Inc. | Method and device for ultrasound drug delivery |
US6533803B2 (en) | 2000-12-22 | 2003-03-18 | Advanced Medical Applications, Inc. | Wound treatment method and device with combination of ultrasound and laser energy |
US6761729B2 (en) | 2000-12-22 | 2004-07-13 | Advanced Medicalapplications, Inc. | Wound treatment method and device with combination of ultrasound and laser energy |
US7914470B2 (en) * | 2001-01-12 | 2011-03-29 | Celleration, Inc. | Ultrasonic method and device for wound treatment |
US8235919B2 (en) * | 2001-01-12 | 2012-08-07 | Celleration, Inc. | Ultrasonic method and device for wound treatment |
US6569099B1 (en) | 2001-01-12 | 2003-05-27 | Eilaz Babaev | Ultrasonic method and device for wound treatment |
IL141123A0 (en) * | 2001-01-26 | 2002-02-10 | Iger Yoni | Method and apparatus for the delivery of substances to biological components |
US6960173B2 (en) * | 2001-01-30 | 2005-11-01 | Eilaz Babaev | Ultrasound wound treatment method and device using standing waves |
DE10108798A1 (en) * | 2001-02-19 | 2002-09-26 | Laser & Med Tech Gmbh | Method and device for ultrasound-supported transmembrane medication application in vivo |
US6623444B2 (en) | 2001-03-21 | 2003-09-23 | Advanced Medical Applications, Inc. | Ultrasonic catheter drug delivery method and device |
DE10119522A1 (en) * | 2001-04-20 | 2002-12-05 | Innovacell Biotechnologie Gmbh | Preparation and application of a suspension composition with an ultrasound contrast medium |
US6478754B1 (en) | 2001-04-23 | 2002-11-12 | Advanced Medical Applications, Inc. | Ultrasonic method and device for wound treatment |
US8123789B2 (en) * | 2002-04-29 | 2012-02-28 | Rohit Khanna | Central nervous system cooling catheter |
EP1420643B1 (en) * | 2001-07-10 | 2008-04-23 | Sonogene, LLC | Enhancement of transfection of dna into the liver |
US7141044B2 (en) * | 2001-12-11 | 2006-11-28 | Ekos Corporation | Alternate site gene therapy |
WO2003051208A1 (en) | 2001-12-14 | 2003-06-26 | Ekos Corporation | Blood flow reestablishment determination |
IL148299A (en) * | 2002-02-21 | 2014-04-30 | Technion Res & Dev Foundation | Ultrasound cardiac stimulator |
US8226629B1 (en) | 2002-04-01 | 2012-07-24 | Ekos Corporation | Ultrasonic catheter power control |
US20040126400A1 (en) * | 2002-05-03 | 2004-07-01 | Iversen Patrick L. | Delivery of therapeutic compounds via microparticles or microbubbles |
JP4243499B2 (en) * | 2002-06-11 | 2009-03-25 | 富士通株式会社 | Bonded substrate manufacturing apparatus and bonded substrate manufacturing method |
EP1575657A2 (en) * | 2002-07-22 | 2005-09-21 | Hans-Werner Bender | Ultrasonic applicator device with a flat, flexible ultrasonic applicator and cavitation medium |
US6921371B2 (en) * | 2002-10-14 | 2005-07-26 | Ekos Corporation | Ultrasound radiating members for catheter |
ES2279178T3 (en) * | 2002-11-04 | 2007-08-16 | Ashland Licensing And Intellectual Property Llc | DEVICE AND PROCEDURE FOR THE TREATMENT OF A LIQUID LIQUID BY ULTRASOUND IN THE PREVENTION OF THE GROWTH OF HYPERPROLIFERATIVE OR INFECTED CELLS. |
JP2004182728A (en) * | 2002-11-22 | 2004-07-02 | Katsuro Tachibana | Drug to be introduced tooth or periodontal tissue and apparatus for introducing drug to tooth or periodontal tissue |
WO2004073647A2 (en) * | 2003-02-19 | 2004-09-02 | Second Stage Ventures, Inc. | Ultrasonically enhanced saline treatment for burn damaged skin |
EP1629105B1 (en) | 2003-04-29 | 2010-09-01 | AVI BioPharma, Inc. | Compositions for enhancing transport and antisense efficacy of nucleic acid analog into cells |
US7048863B2 (en) * | 2003-07-08 | 2006-05-23 | Ashland Licensing And Intellectual Property Llc | Device and process for treating cutting fluids using ultrasound |
WO2005056105A2 (en) * | 2003-12-11 | 2005-06-23 | Hans-Werner Bender | Device consisting of a sonic applicator and a carrier element |
US20060058708A1 (en) * | 2003-12-24 | 2006-03-16 | Gill Heart | Method and apparatus for ultrasonically increasing the transportation of therapeutic substances through tissue |
CA2553165A1 (en) | 2004-01-29 | 2005-08-11 | Ekos Corporation | Method and apparatus for detecting vascular conditions with a catheter |
US7341569B2 (en) | 2004-01-30 | 2008-03-11 | Ekos Corporation | Treatment of vascular occlusions using ultrasonic energy and microbubbles |
CA2579771C (en) | 2004-06-23 | 2012-12-04 | Ashland Licensing And Intellectual Property Llc | Devices and methods for treating fluids utilized in electrocoating processes with ultrasound |
US20060094945A1 (en) * | 2004-10-28 | 2006-05-04 | Sontra Medical Corporation | System and method for analyte sampling and analysis |
JP2008520473A (en) | 2004-11-17 | 2008-06-19 | アシュランド・ライセンシング・アンド・インテレクチュアル・プロパティー・エルエルシー | Apparatus and method for treating cooling liquid utilized in tire manufacture |
WO2006063199A2 (en) | 2004-12-09 | 2006-06-15 | The Foundry, Inc. | Aortic valve repair |
JP2008536562A (en) * | 2005-04-12 | 2008-09-11 | イコス コーポレイション | Ultrasound catheter provided with a cavity forming propulsion surface |
US7713218B2 (en) | 2005-06-23 | 2010-05-11 | Celleration, Inc. | Removable applicator nozzle for ultrasound wound therapy device |
US7785277B2 (en) * | 2005-06-23 | 2010-08-31 | Celleration, Inc. | Removable applicator nozzle for ultrasound wound therapy device |
US20110160621A1 (en) * | 2005-06-24 | 2011-06-30 | Henry Nita | Methods and apparatus for dissolving intracranial blood clots |
US7717853B2 (en) * | 2005-06-24 | 2010-05-18 | Henry Nita | Methods and apparatus for intracranial ultrasound delivery |
US20070031611A1 (en) * | 2005-08-04 | 2007-02-08 | Babaev Eilaz P | Ultrasound medical stent coating method and device |
US9101949B2 (en) * | 2005-08-04 | 2015-08-11 | Eilaz Babaev | Ultrasonic atomization and/or seperation system |
US7896539B2 (en) * | 2005-08-16 | 2011-03-01 | Bacoustics, Llc | Ultrasound apparatus and methods for mixing liquids and coating stents |
US9358033B2 (en) | 2005-09-07 | 2016-06-07 | Ulthera, Inc. | Fluid-jet dissection system and method for reducing the appearance of cellulite |
US20090093737A1 (en) * | 2007-10-09 | 2009-04-09 | Cabochon Aesthetics, Inc. | Ultrasound apparatus with treatment lens |
US10548659B2 (en) | 2006-01-17 | 2020-02-04 | Ulthera, Inc. | High pressure pre-burst for improved fluid delivery |
US9486274B2 (en) * | 2005-09-07 | 2016-11-08 | Ulthera, Inc. | Dissection handpiece and method for reducing the appearance of cellulite |
US9011473B2 (en) | 2005-09-07 | 2015-04-21 | Ulthera, Inc. | Dissection handpiece and method for reducing the appearance of cellulite |
US8518069B2 (en) | 2005-09-07 | 2013-08-27 | Cabochon Aesthetics, Inc. | Dissection handpiece and method for reducing the appearance of cellulite |
US7967763B2 (en) * | 2005-09-07 | 2011-06-28 | Cabochon Aesthetics, Inc. | Method for treating subcutaneous tissues |
US20070060989A1 (en) * | 2005-09-07 | 2007-03-15 | Deem Mark E | Apparatus and method for disrupting subcutaneous structures |
GB0518273D0 (en) * | 2005-09-08 | 2005-10-19 | Univ Dundee | Apparatus and method for sonoporation |
US8257338B2 (en) * | 2006-10-27 | 2012-09-04 | Artenga, Inc. | Medical microbubble generation |
US7885793B2 (en) | 2007-05-22 | 2011-02-08 | International Business Machines Corporation | Method and system for developing a conceptual model to facilitate generating a business-aligned information technology solution |
US9248317B2 (en) * | 2005-12-02 | 2016-02-02 | Ulthera, Inc. | Devices and methods for selectively lysing cells |
US20080200864A1 (en) * | 2005-12-02 | 2008-08-21 | Cabochon Aesthetics, Inc. | Devices and methods for selectively lysing cells |
US20080200863A1 (en) * | 2005-12-02 | 2008-08-21 | Cabochon Aesthetics, Inc. | Devices and methods for selectively lysing cells |
US20080197517A1 (en) * | 2005-12-02 | 2008-08-21 | Cabochon Aesthetics, Inc. | Devices and methods for selectively lysing cells |
US20080014627A1 (en) * | 2005-12-02 | 2008-01-17 | Cabochon Aesthetics, Inc. | Devices and methods for selectively lysing cells |
US20080195036A1 (en) * | 2005-12-02 | 2008-08-14 | Cabochon Aesthetics, Inc. | Devices and methods for selectively lysing cells |
US7432069B2 (en) * | 2005-12-05 | 2008-10-07 | Sontra Medical Corporation | Biocompatible chemically crosslinked hydrogels for glucose sensing |
WO2007102933A2 (en) * | 2006-01-06 | 2007-09-13 | Imarx Therapeutics, Inc | Composition for ultrasound therapy and pharmaceutical liquid composition containing the same |
WO2007127176A2 (en) | 2006-04-24 | 2007-11-08 | Ekos Corporation | Ultrasound therapy system |
US7431704B2 (en) | 2006-06-07 | 2008-10-07 | Bacoustics, Llc | Apparatus and method for the treatment of tissue with ultrasound energy by direct contact |
US8562547B2 (en) | 2006-06-07 | 2013-10-22 | Eliaz Babaev | Method for debriding wounds |
US20080097316A1 (en) * | 2006-08-21 | 2008-04-24 | Leonid Malinin | Ultrasound catheter |
JP2010501287A (en) | 2006-08-25 | 2010-01-21 | ババエヴ,エイラズ | Portable ultrasound device for wound treatment |
US20080089848A1 (en) * | 2006-10-11 | 2008-04-17 | Dimauro Thomas | Intrathecal injection of microbubbles |
US8192363B2 (en) * | 2006-10-27 | 2012-06-05 | Ekos Corporation | Catheter with multiple ultrasound radiating members |
US20080142616A1 (en) * | 2006-12-15 | 2008-06-19 | Bacoustics Llc | Method of Producing a Directed Spray |
US20080177221A1 (en) * | 2006-12-22 | 2008-07-24 | Celleration, Inc. | Apparatus to prevent applicator re-use |
US8491521B2 (en) | 2007-01-04 | 2013-07-23 | Celleration, Inc. | Removable multi-channel applicator nozzle |
WO2008085911A1 (en) * | 2007-01-04 | 2008-07-17 | Celleration, Inc. | Removable multi-channel applicator nozzle |
ES2538110T3 (en) | 2007-01-08 | 2015-06-17 | Ekos Corporation | Power parameters for ultrasonic catheter |
RU2444980C2 (en) * | 2007-03-07 | 2012-03-20 | Эко Терапьютикс, Инк. | Transdermal system of analite monitoring and methods of analite detection |
AU2008245585B2 (en) | 2007-04-27 | 2011-10-06 | Echo Therapeutics, Inc. | Skin permeation device for analyte sensing or transdermal drug delivery |
US7780095B2 (en) | 2007-07-13 | 2010-08-24 | Bacoustics, Llc | Ultrasound pumping apparatus |
US7753285B2 (en) | 2007-07-13 | 2010-07-13 | Bacoustics, Llc | Echoing ultrasound atomization and/or mixing system |
US20090093723A1 (en) * | 2007-10-05 | 2009-04-09 | Cabochon Aesthetics, Inc. | Ultrasound device including dispenser |
US8439940B2 (en) | 2010-12-22 | 2013-05-14 | Cabochon Aesthetics, Inc. | Dissection handpiece with aspiration means for reducing the appearance of cellulite |
US20090093738A1 (en) * | 2007-10-09 | 2009-04-09 | Cabochon Aesthetics, Inc. | Device and method for monitoring a treatment area |
CN100560157C (en) * | 2007-11-13 | 2009-11-18 | 重庆市生力医疗设备有限公司 | Ultrasonic medicine plaster |
US8262645B2 (en) * | 2007-11-21 | 2012-09-11 | Actuated Medical, Inc. | Devices for clearing blockages in in-situ artificial lumens |
US20090187137A1 (en) * | 2007-12-14 | 2009-07-23 | Kim Volz | Ultrasound pulse shaping |
US20090177122A1 (en) * | 2007-12-28 | 2009-07-09 | Celleration, Inc. | Methods for treating inflammatory skin disorders |
DE102008038309A1 (en) * | 2008-08-19 | 2010-02-25 | Theuer, Axel E., Prof. Dr.-Ing. habil. | Device for destruction of tumor cells or pathogens in the bloodstream |
US20100106063A1 (en) * | 2008-10-29 | 2010-04-29 | Cabochon Aesthetics, Inc. | Ultrasound Enhancing Target for Treating Subcutaneous Tissue |
US8167280B2 (en) * | 2009-03-23 | 2012-05-01 | Cabochon Aesthetics, Inc. | Bubble generator having disposable bubble cartridges |
US20100256596A1 (en) * | 2009-04-07 | 2010-10-07 | Cabochon Aesthetics, Inc. | Fiber growth promoting implants for reducing the appearance of cellulite |
EP2448636B1 (en) | 2009-07-03 | 2014-06-18 | Ekos Corporation | Power parameters for ultrasonic catheter |
US9358064B2 (en) | 2009-08-07 | 2016-06-07 | Ulthera, Inc. | Handpiece and methods for performing subcutaneous surgery |
US11096708B2 (en) | 2009-08-07 | 2021-08-24 | Ulthera, Inc. | Devices and methods for performing subcutaneous surgery |
US9375223B2 (en) | 2009-10-06 | 2016-06-28 | Cardioprolific Inc. | Methods and devices for endovascular therapy |
DE102010013703A1 (en) * | 2010-04-01 | 2012-12-27 | Oncowave Medical AG | Apparatus for diagnosis and therapy of malignant tumor in patient, has ultrasound unit connected to control unit, which is switched to therapy mode to determine tumor-specific frequencies and lethal intensity during sonication of tumor |
CN103228224B (en) | 2010-08-27 | 2015-11-25 | Ekos公司 | Be used for the treatment of the method and apparatus of intracranial hemorrhage |
WO2012087842A1 (en) | 2010-12-23 | 2012-06-28 | The Foundry, Llc | System for mitral valve repair and replacement |
US11458290B2 (en) | 2011-05-11 | 2022-10-04 | Ekos Corporation | Ultrasound system |
JP5872692B2 (en) | 2011-06-21 | 2016-03-01 | トゥエルヴ, インコーポレイテッド | Artificial therapy device |
WO2013053099A1 (en) * | 2011-10-10 | 2013-04-18 | Liu Zheng | Use of microbubble combined with ultrasonic cavitation in liver trauma hemostasis |
AU2012325809B2 (en) | 2011-10-19 | 2016-01-21 | Twelve, Inc. | Devices, systems and methods for heart valve replacement |
US11202704B2 (en) | 2011-10-19 | 2021-12-21 | Twelve, Inc. | Prosthetic heart valve devices, prosthetic mitral valves and associated systems and methods |
US9039757B2 (en) | 2011-10-19 | 2015-05-26 | Twelve, Inc. | Prosthetic heart valve devices, prosthetic mitral valves and associated systems and methods |
US9655722B2 (en) | 2011-10-19 | 2017-05-23 | Twelve, Inc. | Prosthetic heart valve devices, prosthetic mitral valves and associated systems and methods |
CA3090422C (en) | 2011-10-19 | 2023-08-01 | Twelve, Inc. | Prosthetic heart valve devices, prosthetic mitral valves and associated systems and methods |
US9763780B2 (en) | 2011-10-19 | 2017-09-19 | Twelve, Inc. | Devices, systems and methods for heart valve replacement |
US9579198B2 (en) | 2012-03-01 | 2017-02-28 | Twelve, Inc. | Hydraulic delivery systems for prosthetic heart valve devices and associated methods |
US20140128734A1 (en) | 2012-11-05 | 2014-05-08 | Ekos Corporation | Catheter systems and methods |
US9101745B2 (en) | 2013-03-14 | 2015-08-11 | Sonogene Llc | Sonochemical induction of ABCA1 expression and compositions therefor |
CA2902713C (en) | 2013-03-14 | 2021-06-01 | Ekos Corporation | Method and apparatus for drug delivery to a target site |
US10111747B2 (en) | 2013-05-20 | 2018-10-30 | Twelve, Inc. | Implantable heart valve devices, mitral valve repair devices and associated systems and methods |
EP3074089A4 (en) | 2013-11-26 | 2017-07-26 | Alliqua Biomedical, Inc. | Systems and methods for producing and delivering ultrasonic therapies for wound treatment and healing |
US10092742B2 (en) | 2014-09-22 | 2018-10-09 | Ekos Corporation | Catheter system |
US10052394B2 (en) | 2014-11-21 | 2018-08-21 | General Electric Company | Microbubble tether for diagnostic and therapeutic applications |
US10238490B2 (en) | 2015-08-21 | 2019-03-26 | Twelve, Inc. | Implant heart valve devices, mitral valve repair devices and associated systems and methods |
CN116172753A (en) | 2016-04-29 | 2023-05-30 | 美敦力瓦斯科尔勒公司 | Prosthetic heart valve devices having tethered anchors and associated systems and methods |
US10702378B2 (en) | 2017-04-18 | 2020-07-07 | Twelve, Inc. | Prosthetic heart valve device and associated systems and methods |
US10575950B2 (en) | 2017-04-18 | 2020-03-03 | Twelve, Inc. | Hydraulic systems for delivering prosthetic heart valve devices and associated methods |
US10433961B2 (en) | 2017-04-18 | 2019-10-08 | Twelve, Inc. | Delivery systems with tethers for prosthetic heart valve devices and associated methods |
US10792151B2 (en) | 2017-05-11 | 2020-10-06 | Twelve, Inc. | Delivery systems for delivering prosthetic heart valve devices and associated methods |
US10646338B2 (en) | 2017-06-02 | 2020-05-12 | Twelve, Inc. | Delivery systems with telescoping capsules for deploying prosthetic heart valve devices and associated methods |
US10709591B2 (en) | 2017-06-06 | 2020-07-14 | Twelve, Inc. | Crimping device and method for loading stents and prosthetic heart valves |
US10729541B2 (en) | 2017-07-06 | 2020-08-04 | Twelve, Inc. | Prosthetic heart valve devices and associated systems and methods |
US10786352B2 (en) | 2017-07-06 | 2020-09-29 | Twelve, Inc. | Prosthetic heart valve devices and associated systems and methods |
Citations (88)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US2961382A (en) * | 1957-07-25 | 1960-11-22 | Ortho Pharma Corp | Urokinase-a plasmiogen activator and methods of obtaining the same |
US4466442A (en) * | 1981-10-16 | 1984-08-21 | Schering Aktiengesellschaft | Carrier liquid solutions for the production of gas microbubbles, preparation thereof, and use thereof as contrast medium for ultrasonic diagnostics |
US4657756A (en) * | 1980-11-17 | 1987-04-14 | Schering Aktiengesellschaft | Microbubble precursors and apparatus for their production and use |
US4657543A (en) * | 1984-07-23 | 1987-04-14 | Massachusetts Institute Of Technology | Ultrasonically modulated polymeric devices for delivering compositions |
US4750902A (en) * | 1985-08-28 | 1988-06-14 | Sonomed Technology, Inc. | Endoscopic ultrasonic aspirators |
US4762915A (en) * | 1985-01-18 | 1988-08-09 | Liposome Technology, Inc. | Protein-liposome conjugates |
US4772594A (en) * | 1986-03-14 | 1988-09-20 | Fujisawa Pharmaceutical Co., Ltd. | Prodrug compounds, process for the preparation thereof and sustained release preparation comprising the same |
US4774958A (en) * | 1985-12-05 | 1988-10-04 | Feinstein Steven B | Ultrasonic imaging agent and method of preparation |
US4797285A (en) * | 1985-12-06 | 1989-01-10 | Yissum Research And Development Company Of The Hebrew University Of Jerusalem | Lipsome/anthraquinone drug composition and method |
US4821740A (en) * | 1986-11-26 | 1989-04-18 | Shunro Tachibana | Endermic application kits for external medicines |
US4844882A (en) * | 1987-12-29 | 1989-07-04 | Molecular Biosystems, Inc. | Concentrated stabilized microbubble-type ultrasonic imaging agent |
US4900540A (en) * | 1983-06-20 | 1990-02-13 | Trustees Of The University Of Massachusetts | Lipisomes containing gas for ultrasound detection |
US4920954A (en) * | 1988-08-05 | 1990-05-01 | Sonic Needle Corporation | Ultrasonic device for applying cavitation forces |
US4921478A (en) * | 1988-02-23 | 1990-05-01 | C. R. Bard, Inc. | Cerebral balloon angioplasty system |
US4936281A (en) * | 1989-04-13 | 1990-06-26 | Everest Medical Corporation | Ultrasonically enhanced RF ablation catheter |
US4948587A (en) * | 1986-07-08 | 1990-08-14 | Massachusetts Institute Of Technology | Ultrasound enhancement of transbuccal drug delivery |
US5040537A (en) * | 1987-11-24 | 1991-08-20 | Hitachi, Ltd. | Method and apparatus for the measurement and medical treatment using an ultrasonic wave |
US5069664A (en) * | 1990-01-25 | 1991-12-03 | Inter Therapy, Inc. | Intravascular ultrasonic angioplasty probe |
US5088499A (en) * | 1989-12-22 | 1992-02-18 | Unger Evan C | Liposomes as contrast agents for ultrasonic imaging and methods for preparing the same |
US5129883A (en) * | 1990-07-26 | 1992-07-14 | Michael Black | Catheter |
US5149319A (en) * | 1990-09-11 | 1992-09-22 | Unger Evan C | Methods for providing localized therapeutic heat to biological tissues and fluids |
US5156050A (en) * | 1990-03-16 | 1992-10-20 | Siemens Aktiengesellschaft | Ultrasonic probe and method for operating the same |
US5158071A (en) * | 1988-07-01 | 1992-10-27 | Hitachi, Ltd. | Ultrasonic apparatus for therapeutical use |
US5197946A (en) * | 1990-06-27 | 1993-03-30 | Shunro Tachibana | Injection instrument with ultrasonic oscillating element |
US5209720A (en) * | 1989-12-22 | 1993-05-11 | Unger Evan C | Methods for providing localized therapeutic heat to biological tissues and fluids using gas filled liposomes |
US5216130A (en) * | 1990-05-17 | 1993-06-01 | Albany Medical College | Complex for in-vivo target localization |
US5215680A (en) * | 1990-07-10 | 1993-06-01 | Cavitation-Control Technology, Inc. | Method for the production of medical-grade lipid-coated microbubbles, paramagnetic labeling of such microbubbles and therapeutic uses of microbubbles |
US5261291A (en) * | 1992-08-17 | 1993-11-16 | Schoch Paul T | Ergonomic apparatus for controlling a vehicle |
US5269291A (en) * | 1990-12-10 | 1993-12-14 | Coraje, Inc. | Miniature ultrasonic transducer for plaque ablation |
US5277913A (en) * | 1991-09-09 | 1994-01-11 | Thompson David H | Liposomal delivery system with photoactivatable triggered release |
US5315998A (en) * | 1991-03-22 | 1994-05-31 | Katsuro Tachibana | Booster for therapy of diseases with ultrasound and pharmaceutical liquid composition containing the same |
US5318014A (en) * | 1992-09-14 | 1994-06-07 | Coraje, Inc. | Ultrasonic ablation/dissolution transducer |
US5342292A (en) * | 1991-11-04 | 1994-08-30 | Baxter International Inc. | Ultrasonic ablation device adapted for guidewire passage |
US5342608A (en) * | 1992-03-19 | 1994-08-30 | Nippon Paint Co., Ltd. | Gas containing contrast agent particles having external magnetic layer |
US5362309A (en) * | 1992-09-14 | 1994-11-08 | Coraje, Inc. | Apparatus and method for enhanced intravascular phonophoresis including dissolution of intravascular blockage and concomitant inhibition of restenosis |
US5368036A (en) * | 1992-10-20 | 1994-11-29 | Fuji Photo Optical Co., Ltd. | Ultrasound probe |
US5380273A (en) * | 1992-05-19 | 1995-01-10 | Dubrul; Will R. | Vibrating catheter |
US5440914A (en) * | 1993-07-21 | 1995-08-15 | Tachibana; Katsuro | Method of measuring distribution and intensity of ultrasonic waves |
US5542935A (en) * | 1989-12-22 | 1996-08-06 | Imarx Pharmaceutical Corp. | Therapeutic delivery systems related applications |
US5558092A (en) * | 1995-06-06 | 1996-09-24 | Imarx Pharmaceutical Corp. | Methods and apparatus for performing diagnostic and therapeutic ultrasound simultaneously |
US5580575A (en) * | 1989-12-22 | 1996-12-03 | Imarx Pharmaceutical Corp. | Therapeutic drug delivery systems |
US5585112A (en) * | 1989-12-22 | 1996-12-17 | Imarx Pharmaceutical Corp. | Method of preparing gas and gaseous precursor-filled microspheres |
US5628728A (en) * | 1995-05-31 | 1997-05-13 | Ekos Corporation | Medicine applying tool |
US5630837A (en) * | 1993-07-01 | 1997-05-20 | Boston Scientific Corporation | Acoustic ablation |
US5648098A (en) * | 1995-10-17 | 1997-07-15 | The Board Of Regents Of The University Of Nebraska | Thrombolytic agents and methods of treatment for thrombosis |
US5695460A (en) * | 1994-09-09 | 1997-12-09 | Coraje, Inc. | Enhancement of ultrasound thrombolysis |
US5707608A (en) * | 1995-08-02 | 1998-01-13 | Qlt Phototherapeutics, Inc. | Methods of making liposomes containing hydro-monobenzoporphyrin photosensitizer |
US5713848A (en) * | 1993-05-19 | 1998-02-03 | Dubrul; Will R. | Vibrating catheter |
US5718921A (en) * | 1987-03-13 | 1998-02-17 | Massachusetts Institute Of Technology | Microspheres comprising polymer and drug dispersed there within |
US5733572A (en) * | 1989-12-22 | 1998-03-31 | Imarx Pharmaceutical Corp. | Gas and gaseous precursor filled microspheres as topical and subcutaneous delivery vehicles |
US5735811A (en) * | 1995-11-30 | 1998-04-07 | Pharmasonics, Inc. | Apparatus and methods for ultrasonically enhanced fluid delivery |
US5776429A (en) * | 1989-12-22 | 1998-07-07 | Imarx Pharmaceutical Corp. | Method of preparing gas-filled microspheres using a lyophilized lipids |
US5817048A (en) * | 1997-03-20 | 1998-10-06 | Brown University Research Foundation | Ultrasonic alternative to laser-based photodynamic therapy |
US5836896A (en) * | 1996-08-19 | 1998-11-17 | Angiosonics | Method of inhibiting restenosis by applying ultrasonic energy |
US5916192A (en) * | 1991-01-11 | 1999-06-29 | Advanced Cardiovascular Systems, Inc. | Ultrasonic angioplasty-atherectomy catheter and method of use |
US5997497A (en) * | 1991-01-11 | 1999-12-07 | Advanced Cardiovascular Systems | Ultrasound catheter having integrated drug delivery system and methods of using same |
US6001069A (en) * | 1997-05-01 | 1999-12-14 | Ekos Corporation | Ultrasound catheter for providing a therapeutic effect to a vessel of a body |
US6007514A (en) * | 1997-09-30 | 1999-12-28 | Nita; Henry | Ultrasound system with pathfinding guidewire |
US6024718A (en) * | 1996-09-04 | 2000-02-15 | The Regents Of The University Of California | Intraluminal directed ultrasound delivery device |
US6068857A (en) * | 1993-09-09 | 2000-05-30 | Schering Aktiengesellchaft | Microparticles containing active ingredients, agents containing these microparticles, their use for ultrasound-controlled release of active ingredients, as well as a process for their production |
US6096000A (en) * | 1997-06-23 | 2000-08-01 | Ekos Corporation | Apparatus for transport of fluids across, into or from biological tissues |
US6096070A (en) * | 1995-06-07 | 2000-08-01 | Med Institute Inc. | Coated implantable medical device |
US6113558A (en) * | 1997-09-29 | 2000-09-05 | Angiosonics Inc. | Pulsed mode lysis method |
US6135976A (en) * | 1998-09-25 | 2000-10-24 | Ekos Corporation | Method, device and kit for performing gene therapy |
US6176842B1 (en) * | 1995-03-08 | 2001-01-23 | Ekos Corporation | Ultrasound assembly for use with light activated drugs |
US6210356B1 (en) * | 1998-08-05 | 2001-04-03 | Ekos Corporation | Ultrasound assembly for use with a catheter |
US6228046B1 (en) * | 1997-06-02 | 2001-05-08 | Pharmasonics, Inc. | Catheters comprising a plurality of oscillators and methods for their use |
US20010003790A1 (en) * | 1996-02-15 | 2001-06-14 | Shlomo Ben-Haim | Catheter based surgery |
US6296619B1 (en) * | 1998-12-30 | 2001-10-02 | Pharmasonics, Inc. | Therapeutic ultrasonic catheter for delivering a uniform energy dose |
US20010053384A1 (en) * | 1997-07-07 | 2001-12-20 | James F. Greenleaf | Site-directed transfection with ultrasound and cavitation nuclei |
US20020041898A1 (en) * | 2000-01-05 | 2002-04-11 | Unger Evan C. | Novel targeted delivery systems for bioactive agents |
US6416740B1 (en) * | 1997-05-13 | 2002-07-09 | Bristol-Myers Squibb Medical Imaging, Inc. | Acoustically active drug delivery systems |
US20020151792A1 (en) * | 1998-02-06 | 2002-10-17 | Conston Stanley R. | Method for ultrasound triggered drug delivery using hollow microbubbles with controlled fragility |
US6508816B2 (en) * | 1998-03-27 | 2003-01-21 | John H. Shadduck | Medical instrument working end creating very high pressure gradients |
US6524251B2 (en) * | 1999-10-05 | 2003-02-25 | Omnisonics Medical Technologies, Inc. | Ultrasonic device for tissue ablation and sheath for use therewith |
US6548047B1 (en) * | 1997-09-15 | 2003-04-15 | Bristol-Myers Squibb Medical Imaging, Inc. | Thermal preactivation of gaseous precursor filled compositions |
US6582392B1 (en) * | 1998-05-01 | 2003-06-24 | Ekos Corporation | Ultrasound assembly for use with a catheter |
US20030139774A1 (en) * | 1998-06-03 | 2003-07-24 | Epstein Gordon Howard | Direct dual filling device for sealing agents |
US6676626B1 (en) * | 1998-05-01 | 2004-01-13 | Ekos Corporation | Ultrasound assembly with increased efficacy |
US20040019318A1 (en) * | 2001-11-07 | 2004-01-29 | Wilson Richard R. | Ultrasound assembly for use with a catheter |
US20040024347A1 (en) * | 2001-12-03 | 2004-02-05 | Wilson Richard R. | Catheter with multiple ultrasound radiating members |
US20040049148A1 (en) * | 2001-12-03 | 2004-03-11 | Oscar Rodriguez | Small vessel ultrasound catheter |
US20040068189A1 (en) * | 2002-02-28 | 2004-04-08 | Wilson Richard R. | Ultrasound catheter with embedded conductors |
US6723063B1 (en) * | 1998-06-29 | 2004-04-20 | Ekos Corporation | Sheath for use with an ultrasound element |
US20050090818A1 (en) * | 2003-10-27 | 2005-04-28 | Pike Robert W.Jr. | Method for ablating with needle electrode |
US20060264809A1 (en) * | 2005-04-12 | 2006-11-23 | Hansmann Douglas R | Ultrasound catheter with cavitation promoting surface |
US20070083120A1 (en) * | 2005-09-22 | 2007-04-12 | Cain Charles A | Pulsed cavitational ultrasound therapy |
US7341569B2 (en) * | 2004-01-30 | 2008-03-11 | Ekos Corporation | Treatment of vascular occlusions using ultrasonic energy and microbubbles |
Family Cites Families (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US558512A (en) * | 1896-04-21 | Strainer for coffee-pots | ||
CA1083040A (en) * | 1976-02-09 | 1980-08-05 | Mostafa Fahim | Topical application of medication by ultrasound with coupling agent |
FR2445755A1 (en) | 1979-01-08 | 1980-08-01 | Harmand Pierre | TOOL HOLDER SPINDLE FOR PRECISION MACHINING |
US4276885A (en) * | 1979-05-04 | 1981-07-07 | Rasor Associates, Inc | Ultrasonic image enhancement |
DE3741201A1 (en) * | 1987-12-02 | 1989-06-15 | Schering Ag | ULTRASONIC PROCESS AND METHOD FOR IMPLEMENTING IT |
DE3741199A1 (en) * | 1987-12-02 | 1989-08-17 | Schering Ag | USE OF ULTRASONIC CONTRASTING AGENTS FOR ULTRASONIC LITHOTRIPSY |
KR0133132B1 (en) * | 1988-02-05 | 1998-04-17 | 쉐링 아게, 베를린 운트 베르크카멘 | Ultrasonic contrast agents, process for producing them and their use as diagnostics |
JPH02180275A (en) * | 1988-12-29 | 1990-07-13 | Toshiro Tachibana | Medicine injection tool having ultrasonic wave oscillation element |
-
1992
- 1992-03-19 DE DE69215722T patent/DE69215722T3/en not_active Expired - Fee Related
- 1992-03-19 AT AT92104789T patent/ATE146073T1/en active
- 1992-03-19 CA CA002063529A patent/CA2063529A1/en not_active Abandoned
- 1992-03-19 EP EP96108580A patent/EP0732106A3/en not_active Withdrawn
- 1992-03-19 EP EP92104789A patent/EP0504881B2/en not_active Expired - Lifetime
- 1992-03-20 US US07/855,545 patent/US5315998A/en not_active Ceased
-
1996
- 1996-05-30 US US08/652,690 patent/USRE36939E/en not_active Expired - Lifetime
-
1999
- 1999-08-16 US US09/375,339 patent/US6585678B1/en not_active Expired - Fee Related
-
2003
- 2003-03-26 US US10/400,337 patent/US20030191446A1/en not_active Abandoned
-
2008
- 2008-07-14 US US12/172,686 patent/US20080274097A1/en not_active Abandoned
Patent Citations (99)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US2961382A (en) * | 1957-07-25 | 1960-11-22 | Ortho Pharma Corp | Urokinase-a plasmiogen activator and methods of obtaining the same |
US4657756A (en) * | 1980-11-17 | 1987-04-14 | Schering Aktiengesellschaft | Microbubble precursors and apparatus for their production and use |
US4466442A (en) * | 1981-10-16 | 1984-08-21 | Schering Aktiengesellschaft | Carrier liquid solutions for the production of gas microbubbles, preparation thereof, and use thereof as contrast medium for ultrasonic diagnostics |
US4900540A (en) * | 1983-06-20 | 1990-02-13 | Trustees Of The University Of Massachusetts | Lipisomes containing gas for ultrasound detection |
US4657543A (en) * | 1984-07-23 | 1987-04-14 | Massachusetts Institute Of Technology | Ultrasonically modulated polymeric devices for delivering compositions |
US4762915A (en) * | 1985-01-18 | 1988-08-09 | Liposome Technology, Inc. | Protein-liposome conjugates |
US4750902A (en) * | 1985-08-28 | 1988-06-14 | Sonomed Technology, Inc. | Endoscopic ultrasonic aspirators |
US4774958A (en) * | 1985-12-05 | 1988-10-04 | Feinstein Steven B | Ultrasonic imaging agent and method of preparation |
US4797285A (en) * | 1985-12-06 | 1989-01-10 | Yissum Research And Development Company Of The Hebrew University Of Jerusalem | Lipsome/anthraquinone drug composition and method |
US4772594A (en) * | 1986-03-14 | 1988-09-20 | Fujisawa Pharmaceutical Co., Ltd. | Prodrug compounds, process for the preparation thereof and sustained release preparation comprising the same |
US4948587A (en) * | 1986-07-08 | 1990-08-14 | Massachusetts Institute Of Technology | Ultrasound enhancement of transbuccal drug delivery |
US4953565A (en) * | 1986-11-26 | 1990-09-04 | Shunro Tachibana | Endermic application kits for external medicines |
US4821740A (en) * | 1986-11-26 | 1989-04-18 | Shunro Tachibana | Endermic application kits for external medicines |
US5007438A (en) * | 1986-11-26 | 1991-04-16 | Shunro Tachibana | Endermic application kits for external medicines |
US5718921A (en) * | 1987-03-13 | 1998-02-17 | Massachusetts Institute Of Technology | Microspheres comprising polymer and drug dispersed there within |
US5040537A (en) * | 1987-11-24 | 1991-08-20 | Hitachi, Ltd. | Method and apparatus for the measurement and medical treatment using an ultrasonic wave |
US4844882A (en) * | 1987-12-29 | 1989-07-04 | Molecular Biosystems, Inc. | Concentrated stabilized microbubble-type ultrasonic imaging agent |
US4921478A (en) * | 1988-02-23 | 1990-05-01 | C. R. Bard, Inc. | Cerebral balloon angioplasty system |
US5158071A (en) * | 1988-07-01 | 1992-10-27 | Hitachi, Ltd. | Ultrasonic apparatus for therapeutical use |
US4920954A (en) * | 1988-08-05 | 1990-05-01 | Sonic Needle Corporation | Ultrasonic device for applying cavitation forces |
US4936281A (en) * | 1989-04-13 | 1990-06-26 | Everest Medical Corporation | Ultrasonically enhanced RF ablation catheter |
US5733572A (en) * | 1989-12-22 | 1998-03-31 | Imarx Pharmaceutical Corp. | Gas and gaseous precursor filled microspheres as topical and subcutaneous delivery vehicles |
US5776429A (en) * | 1989-12-22 | 1998-07-07 | Imarx Pharmaceutical Corp. | Method of preparing gas-filled microspheres using a lyophilized lipids |
US5088499A (en) * | 1989-12-22 | 1992-02-18 | Unger Evan C | Liposomes as contrast agents for ultrasonic imaging and methods for preparing the same |
US5209720A (en) * | 1989-12-22 | 1993-05-11 | Unger Evan C | Methods for providing localized therapeutic heat to biological tissues and fluids using gas filled liposomes |
US5542935A (en) * | 1989-12-22 | 1996-08-06 | Imarx Pharmaceutical Corp. | Therapeutic delivery systems related applications |
US5585112A (en) * | 1989-12-22 | 1996-12-17 | Imarx Pharmaceutical Corp. | Method of preparing gas and gaseous precursor-filled microspheres |
US5580575A (en) * | 1989-12-22 | 1996-12-03 | Imarx Pharmaceutical Corp. | Therapeutic drug delivery systems |
US5069664A (en) * | 1990-01-25 | 1991-12-03 | Inter Therapy, Inc. | Intravascular ultrasonic angioplasty probe |
US5156050A (en) * | 1990-03-16 | 1992-10-20 | Siemens Aktiengesellschaft | Ultrasonic probe and method for operating the same |
US5216130A (en) * | 1990-05-17 | 1993-06-01 | Albany Medical College | Complex for in-vivo target localization |
US5197946A (en) * | 1990-06-27 | 1993-03-30 | Shunro Tachibana | Injection instrument with ultrasonic oscillating element |
US5215680A (en) * | 1990-07-10 | 1993-06-01 | Cavitation-Control Technology, Inc. | Method for the production of medical-grade lipid-coated microbubbles, paramagnetic labeling of such microbubbles and therapeutic uses of microbubbles |
US5129883A (en) * | 1990-07-26 | 1992-07-14 | Michael Black | Catheter |
US5149319A (en) * | 1990-09-11 | 1992-09-22 | Unger Evan C | Methods for providing localized therapeutic heat to biological tissues and fluids |
US5431663A (en) * | 1990-12-10 | 1995-07-11 | Coraje, Inc. | Miniature ultrasonic transducer for removal of intravascular plaque and clots |
US5269291A (en) * | 1990-12-10 | 1993-12-14 | Coraje, Inc. | Miniature ultrasonic transducer for plaque ablation |
US5997497A (en) * | 1991-01-11 | 1999-12-07 | Advanced Cardiovascular Systems | Ultrasound catheter having integrated drug delivery system and methods of using same |
US5916192A (en) * | 1991-01-11 | 1999-06-29 | Advanced Cardiovascular Systems, Inc. | Ultrasonic angioplasty-atherectomy catheter and method of use |
USRE36939E (en) * | 1991-03-22 | 2000-10-31 | Ekos Corporation | Composition for therapy of diseases with ultrasonic and pharmaceutical liquid composition containing the same |
US5315998A (en) * | 1991-03-22 | 1994-05-31 | Katsuro Tachibana | Booster for therapy of diseases with ultrasound and pharmaceutical liquid composition containing the same |
US20030191446A1 (en) * | 1991-03-22 | 2003-10-09 | Katsuro Tachibana | Booster for therapy of diseases with ultrasound and pharmaceutical liquid composition containing the same |
US6585678B1 (en) * | 1991-03-22 | 2003-07-01 | Ekos Corporation | Booster for therapy of disease with ultrasound and pharmaceutical IDLIQU composition containing the same |
US5277913A (en) * | 1991-09-09 | 1994-01-11 | Thompson David H | Liposomal delivery system with photoactivatable triggered release |
US5342292A (en) * | 1991-11-04 | 1994-08-30 | Baxter International Inc. | Ultrasonic ablation device adapted for guidewire passage |
US5342608A (en) * | 1992-03-19 | 1994-08-30 | Nippon Paint Co., Ltd. | Gas containing contrast agent particles having external magnetic layer |
US5380273A (en) * | 1992-05-19 | 1995-01-10 | Dubrul; Will R. | Vibrating catheter |
US5261291A (en) * | 1992-08-17 | 1993-11-16 | Schoch Paul T | Ergonomic apparatus for controlling a vehicle |
US5318014A (en) * | 1992-09-14 | 1994-06-07 | Coraje, Inc. | Ultrasonic ablation/dissolution transducer |
US5362309A (en) * | 1992-09-14 | 1994-11-08 | Coraje, Inc. | Apparatus and method for enhanced intravascular phonophoresis including dissolution of intravascular blockage and concomitant inhibition of restenosis |
US5474531A (en) * | 1992-09-14 | 1995-12-12 | Coraje, Inc. | Apparatus and method for enhanced intravascular phonophoresis including dissolution of intravascular blockage and concomitant inhibition of restenosis |
US5368036A (en) * | 1992-10-20 | 1994-11-29 | Fuji Photo Optical Co., Ltd. | Ultrasound probe |
US5713848A (en) * | 1993-05-19 | 1998-02-03 | Dubrul; Will R. | Vibrating catheter |
US5630837A (en) * | 1993-07-01 | 1997-05-20 | Boston Scientific Corporation | Acoustic ablation |
US5440914A (en) * | 1993-07-21 | 1995-08-15 | Tachibana; Katsuro | Method of measuring distribution and intensity of ultrasonic waves |
US6068857A (en) * | 1993-09-09 | 2000-05-30 | Schering Aktiengesellchaft | Microparticles containing active ingredients, agents containing these microparticles, their use for ultrasound-controlled release of active ingredients, as well as a process for their production |
US5695460A (en) * | 1994-09-09 | 1997-12-09 | Coraje, Inc. | Enhancement of ultrasound thrombolysis |
US6176842B1 (en) * | 1995-03-08 | 2001-01-23 | Ekos Corporation | Ultrasound assembly for use with light activated drugs |
US5628728A (en) * | 1995-05-31 | 1997-05-13 | Ekos Corporation | Medicine applying tool |
US5558092A (en) * | 1995-06-06 | 1996-09-24 | Imarx Pharmaceutical Corp. | Methods and apparatus for performing diagnostic and therapeutic ultrasound simultaneously |
US6096070A (en) * | 1995-06-07 | 2000-08-01 | Med Institute Inc. | Coated implantable medical device |
US6287271B1 (en) * | 1995-06-07 | 2001-09-11 | Bacchus Vascular, Inc. | Motion catheter |
US5707608A (en) * | 1995-08-02 | 1998-01-13 | Qlt Phototherapeutics, Inc. | Methods of making liposomes containing hydro-monobenzoporphyrin photosensitizer |
US5648098A (en) * | 1995-10-17 | 1997-07-15 | The Board Of Regents Of The University Of Nebraska | Thrombolytic agents and methods of treatment for thrombosis |
US5735811A (en) * | 1995-11-30 | 1998-04-07 | Pharmasonics, Inc. | Apparatus and methods for ultrasonically enhanced fluid delivery |
US20010003790A1 (en) * | 1996-02-15 | 2001-06-14 | Shlomo Ben-Haim | Catheter based surgery |
US5836896A (en) * | 1996-08-19 | 1998-11-17 | Angiosonics | Method of inhibiting restenosis by applying ultrasonic energy |
US6024718A (en) * | 1996-09-04 | 2000-02-15 | The Regents Of The University Of California | Intraluminal directed ultrasound delivery device |
US5817048A (en) * | 1997-03-20 | 1998-10-06 | Brown University Research Foundation | Ultrasonic alternative to laser-based photodynamic therapy |
US6001069A (en) * | 1997-05-01 | 1999-12-14 | Ekos Corporation | Ultrasound catheter for providing a therapeutic effect to a vessel of a body |
US6416740B1 (en) * | 1997-05-13 | 2002-07-09 | Bristol-Myers Squibb Medical Imaging, Inc. | Acoustically active drug delivery systems |
US6228046B1 (en) * | 1997-06-02 | 2001-05-08 | Pharmasonics, Inc. | Catheters comprising a plurality of oscillators and methods for their use |
US6096000A (en) * | 1997-06-23 | 2000-08-01 | Ekos Corporation | Apparatus for transport of fluids across, into or from biological tissues |
US20010053384A1 (en) * | 1997-07-07 | 2001-12-20 | James F. Greenleaf | Site-directed transfection with ultrasound and cavitation nuclei |
US6548047B1 (en) * | 1997-09-15 | 2003-04-15 | Bristol-Myers Squibb Medical Imaging, Inc. | Thermal preactivation of gaseous precursor filled compositions |
US6113558A (en) * | 1997-09-29 | 2000-09-05 | Angiosonics Inc. | Pulsed mode lysis method |
US6007514A (en) * | 1997-09-30 | 1999-12-28 | Nita; Henry | Ultrasound system with pathfinding guidewire |
US6896659B2 (en) * | 1998-02-06 | 2005-05-24 | Point Biomedical Corporation | Method for ultrasound triggered drug delivery using hollow microbubbles with controlled fragility |
US20020151792A1 (en) * | 1998-02-06 | 2002-10-17 | Conston Stanley R. | Method for ultrasound triggered drug delivery using hollow microbubbles with controlled fragility |
US6508816B2 (en) * | 1998-03-27 | 2003-01-21 | John H. Shadduck | Medical instrument working end creating very high pressure gradients |
US6676626B1 (en) * | 1998-05-01 | 2004-01-13 | Ekos Corporation | Ultrasound assembly with increased efficacy |
US6582392B1 (en) * | 1998-05-01 | 2003-06-24 | Ekos Corporation | Ultrasound assembly for use with a catheter |
US20030139774A1 (en) * | 1998-06-03 | 2003-07-24 | Epstein Gordon Howard | Direct dual filling device for sealing agents |
US6723063B1 (en) * | 1998-06-29 | 2004-04-20 | Ekos Corporation | Sheath for use with an ultrasound element |
US6210356B1 (en) * | 1998-08-05 | 2001-04-03 | Ekos Corporation | Ultrasound assembly for use with a catheter |
US6135976A (en) * | 1998-09-25 | 2000-10-24 | Ekos Corporation | Method, device and kit for performing gene therapy |
US6296619B1 (en) * | 1998-12-30 | 2001-10-02 | Pharmasonics, Inc. | Therapeutic ultrasonic catheter for delivering a uniform energy dose |
US6524251B2 (en) * | 1999-10-05 | 2003-02-25 | Omnisonics Medical Technologies, Inc. | Ultrasonic device for tissue ablation and sheath for use therewith |
US20020041898A1 (en) * | 2000-01-05 | 2002-04-11 | Unger Evan C. | Novel targeted delivery systems for bioactive agents |
US20040019318A1 (en) * | 2001-11-07 | 2004-01-29 | Wilson Richard R. | Ultrasound assembly for use with a catheter |
US7220239B2 (en) * | 2001-12-03 | 2007-05-22 | Ekos Corporation | Catheter with multiple ultrasound radiating members |
US20040024347A1 (en) * | 2001-12-03 | 2004-02-05 | Wilson Richard R. | Catheter with multiple ultrasound radiating members |
US20040049148A1 (en) * | 2001-12-03 | 2004-03-11 | Oscar Rodriguez | Small vessel ultrasound catheter |
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US20050090818A1 (en) * | 2003-10-27 | 2005-04-28 | Pike Robert W.Jr. | Method for ablating with needle electrode |
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US20060264809A1 (en) * | 2005-04-12 | 2006-11-23 | Hansmann Douglas R | Ultrasound catheter with cavitation promoting surface |
US20070083120A1 (en) * | 2005-09-22 | 2007-04-12 | Cain Charles A | Pulsed cavitational ultrasound therapy |
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US10926074B2 (en) | 2001-12-03 | 2021-02-23 | Ekos Corporation | Catheter with multiple ultrasound radiating members |
US11925367B2 (en) | 2007-01-08 | 2024-03-12 | Ekos Corporation | Power parameters for ultrasonic catheter |
US11672553B2 (en) | 2007-06-22 | 2023-06-13 | Ekos Corporation | Method and apparatus for treatment of intracranial hemorrhages |
US8740835B2 (en) | 2010-02-17 | 2014-06-03 | Ekos Corporation | Treatment of vascular occlusions using ultrasonic energy and microbubbles |
US9192566B2 (en) | 2010-02-17 | 2015-11-24 | Ekos Corporation | Treatment of vascular occlusions using ultrasonic energy and microbubbles |
US10656025B2 (en) | 2015-06-10 | 2020-05-19 | Ekos Corporation | Ultrasound catheter |
US11740138B2 (en) | 2015-06-10 | 2023-08-29 | Ekos Corporation | Ultrasound catheter |
Also Published As
Publication number | Publication date |
---|---|
US6585678B1 (en) | 2003-07-01 |
USRE36939E (en) | 2000-10-31 |
CA2063529A1 (en) | 1992-09-23 |
DE69215722D1 (en) | 1997-01-23 |
EP0504881A2 (en) | 1992-09-23 |
EP0504881A3 (en) | 1993-04-14 |
EP0732106A2 (en) | 1996-09-18 |
ATE146073T1 (en) | 1996-12-15 |
EP0504881B2 (en) | 2000-11-08 |
EP0732106A3 (en) | 2003-04-09 |
US20030191446A1 (en) | 2003-10-09 |
EP0504881B1 (en) | 1996-12-11 |
US5315998A (en) | 1994-05-31 |
DE69215722T3 (en) | 2001-03-08 |
DE69215722T2 (en) | 1997-05-07 |
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