Massachusetts Institute of Technology

Sontra Medical Corporation

Ben-gurion University of the Negev Research and Development Authority

B.g. Negev Technologies and Applications Ltd.

Echo Therapeutics, Inc.

Other

Ramot at Tel-aviv University Ltd.

Children's Hospital Medical Center

Non-invasive Monitoring Company (nimco)

Joseph Kost

Robert Samuel Langer

Samir Suresh Mitragotri

Scott C Kellogg

Nicholas F Warner

Tuan A Elstrom

Tamar Traitel

Michael V Pishko

Riki Goldbart

Stephen C Rowe

Yana Yudilevich

Matthew Davis

James C Weaver

Dan Peer

Jeffrey A Whitsett

Jonathan A Eppstein

Daniel Blankschtein

Uwe Pliquett

Han Chuang

Linda M Custer

James P Hurley

Deborah A Eppstein

Rom Eliaz

Mark E Johnson

Shani Attias

Eliz Lewis Amar

Paul Scot Kingma

Rinat Lifshiz

Drora Levy

Eden Bergman

Rivka Goldbart

Itay Rousso

Nitzan Marelly

Moshe Elkabets

Israel Patla

Aharon (Roni) Azagury

Avraham Schroeder

Giora Enden

Assaf Rudich

Lior Wolloch

Etili Hollander

Mordechi Hallak

Aharon Azaguri

Nicolas F Warner

Steve DiMatteo

Nitsa Buaron

Provided herein methods for treating a subject suffering from a disease or a disorder associated with hyperproliferating cells, by irradiating the cells with low-frequency ultrasound at an intensity that is either below the cavitational threshold intensity for the ultrasound frequency, or is characterized by a low-frequency mechanical index below 2.5. The methods may further comprise determining an elasticity value of the cells, and adjusting the ultrasound intensity accordingly.

Low intensity ultrasound therapy

Methods of treating a subject suffering from a disease or a disorder associated with hyperproliferating cells. The method includes non-invasively administering to the subject ultrasound at a low intensity in a dose effective to selectively prevent the growth of the hyperproliferating cells or to eliminate the hyperproliferating cells in the subject, while substantially not affecting the cell viability of normal cells of the subject. The low intensity is pre-determined to be lower than a cavitational threshold intensity for a selected frequency.

A controlled release system includes surfactant protein D (SPD) and a carrier suitable for controlled release that can be polylactic-co-glycolic acid (PLGA). The system can be in the form of a nanoparticle. A pharmaceutical composition includes the system and a pharmaceutically acceptable carrier. Methods of treatment of a disease, disorder or condition associated with a decreased level of SPD in a subject, or for pulmonary delivery of SPD, include administering the pharmaceutical composition to a subject in need of such treatment.

Controlled release system for pulmonary delivery of surfactant protein D

The present invention provides a complex comprising at least one phosphoinositide and at least one positively charged modified polysaccharide, pharmaceutical compositions comprising the complex, methods for treatment of a disease, disorder or condition associated with impaired phosphoinositide-mediated signaling comprising administering the complex to an subject in need, and methods for delivery of a phosphoinositide into cells, comprising contacting the cells with the complex of the invention.

Cationic polysaccharides for delivery of phosphoinositides to cells for therapeutic purpose

A complex includes RNA and a positively charged modified polysaccharide selected from starch, amylose, amylopectin, galactan, chitosan, or dextrin. The complex can be formed into a pharmaceutical composition. The complex can be used in methods for RNA transfection, gene therapy and treatment of a disease, disorder or condition. The positively charged modified polysaccharide can be used in connection with RNA transfection into cells.

Positively charged polysaccharides for RNA transfection

According to the present invention, a method for enhancing transdermal transport is disclosed. The method includes the steps of increasing a permeability an area of a membrane with a permeabilizing device. The membrane may be, inter alia, biologic skin or synthetic skin. The permeabilizing device may be an ultrasound-producing device. A substance is transported into and through the area the membrane. The substance may be a drug, a vaccine, or a component of interstitial fluid.

Method and apparatus for enhancement of transdermal transport

Transdermal analyte monitoring systems (TAMS) having increased longevity and improved analyte detection are described herein. Kits for use with the TAMS and methods of using the TAMS and kits are also described. In a preferred embodiment, the TAMS includes a protective, semi-permeable membrane covering the surface of the hydrogel. The protective, semi-permeable membrane contacts with the skin of a user and prevents contamination or fouling of the hydrogel. Optionally, the hydrogel comprises one or more humectants and/or an immobilized enzyme. In another preferred embodiment, the TAMS contains at least one channel or pocket for increasing the amount of oxygen provided to the hydrogel. In one embodiment, a method for improving analyte detection by the TAMS is provided. For example, after the skin porosity is increased by an appropriate pretreatment, a skin preparation wipe is applied to the treated skin area and then the TAMS is applied to the treated area.

Transdermal analyte monitoring systems and methods for analyte detection

The invention provides a system and method for trans-fetal membranes transport. A source of ultrasound sonication is used to deliver ultrasound sonication to fetal membranes to enhance the permeability of the fetal membranes of a gestational sac. In one embodiment, a device is used to collect substances transported from the interior of the gestational sac to the exterior of the gestational sac, such as amniotic or coelomic fluid. In another embodiment a device is used to deliver one or more substances, such as a drug, to an external surface of the fetal membranes.

System and method for transfetal (amnion-chorion) membranes transport

According to the present invention, a method for enhancing transdermal transport is disclosed. The method includes the steps of increasing a permeability of an area of a membrane with a permeabilizing device. The membrane may be, inter alia, biologic skin or synthetic skin. The permeabilizing device may be an ultrasound-producing device. A substance is transported into and through the area of the membrane. The substance may be a drug, a vaccine, or a component of interstitial fluid.

A system, method, and device for non-invasive body fluid sampling is provided. According to one embodiment of the present invention, the system includes a controller that controls the generation of ultrasound; an ultrasonic applicator that applies the ultrasound to an area of biological membrane; a receiver that contacts the area of biological membrane and receives body fluid through and out of the area of biological membrane; and a meter that interacts with the receiver and detects the presence of at least one analyte in the body fluid in the receiver. The receiver may include a membrane and a medium, such as a hydrogel, a fluid, or a liquid, that is contained in the membrane. According to one embodiment of the present invention, the method includes the steps of (1) identifying an area of biological membrane having a permeability level; (2) increasing the permeability level of the area of biological membrane; (3) contacting the area of biological membrane with a receiver; (4) extracting body fluid through and out of the area of biological membrane; (5) providing an external force to enhance the body fluid extraction; (6) collecting the body fluid in the receiver; (7) analyzing the collected body fluid for the presence of at least one analyte; and (8) providing the results of the step of analyzing the body fluid.

System, method, and device for non-invasive body fluid sampling and analysis

The invention provides a convenient and non-invasive means to prepare cells, tissues, and organs for electrical transmission and reception. In an embodiment of the invention, a control method comprises the use of at least one skin electrode, as a reference electrode, and an electrical sensor to measure periodically or continuously the skin's electrical conductance at the site of preparation. The dynamic change in the conductance through the skin is measured while the ultrasound is applied. Signal processing is performed on the measurement and the level of skin impedance change is controlled by performing a mathematical analysis and using the results of such analysis to control the application of ultrasonic energy. A desired level of skin impedance can be set at a predetermined value or based on a chosen level of skin integrity, subject's sensation of discomfort, or duration of the ultrasound application.

Preparation for transmission and reception of electrical signals

The present invention is directed to apparatus and methods for producing homogenous cavitation. An ultrasound souce comprising an ultrasound transmitting element having an axis and a cross-section along the axis is disclosed The ultrasound transmitting element also has a first axial end and a second axial end operable to produce ultrasonic waves. The cross-section has an area having a maximum value at the first axial end and a minimum value at the second axial end. A method for producing homogenous cavitation at an area of skin comprises creating a volume of fluid having a uniformly dispersed concentration of cavitation nuclei adjacent the area of skin. Ultrasound is then applied to the volume of fluid and causes cavitation at the cavitation nuclei.

Method and apparatus for producing homogenous cavitation to enhance transdermal transport

Methods and devices for application of ultrasound to a small area of skin for enhancing transdermal transport. An ultrasound beam having a first focal diameter is channelled into a beam having a second, smaller diameter without substantial loss of energy. Higher energy ultrasound can be used while causing less pain. Alternatively, ultrasound energy is applied through a vibrating element positioned just contacting, above or extending into the skin. Use of the element facilitates extraction of analyte and may enhance drug delivery. A two step noninvasive method involves application of ultrasound to increase skin permeability and removal of ultrasound followed by transdermal transport that can be further enhanced using a physical enhancer.

Ultrasound enhancement of transdermal transport

The invention discloses a composition having a mixture of a pharmaceutically, medically or veterinarily acceptable polymer, preferable a poly (lactic-co-glycolic acid) copolymer (PLGA) containing between about 10 and 100 wt. % lactic acid (LA) units, preferably between about 50 and 90 wt. % LA units, and &agr;-(tetrahydrofuranyl)-&ohgr;-hydroxypoly(oxy-1,2-ethandiyl) (glycofurol). Methods of forming solid implants in situ in an animal body, said implants optionally comprising a drug or other biologically active agent, as well as the use of the compositions of the invention in the treatment of animal bodies, are also disclosed.

Composition and method for forming biodegradable implants in situ and uses of these implants

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Omer, Israel

Joseph Kost