Abstract: Granules are prepared containing an admixture of protein and starch layered over an inert particle. Proteins include pharmaceutically important proteins such as hormones, or industrially important proteins such as enzymes including proteases, amylases, lipases and cellulases capable of hydrolyzing substrates such as stains. Inert particles include inorganic salts, sugars, sugar alcohols, small organic molecules such as organic acids or salts, and minerals such as clays or silicates. The admixture may also contain sugar such as sucrose. A ratio of corn starch to sugar much greater than 1:1 such as in a range of about 5:1 to about 15:1 is preferred. A coating layer may be between the inert particle and the admixture and/or over the admixture. Methods that may be used in preparing the granules include pan-coating, fluid-bed coating, prilling, disc granulation, spray drying, extrusion, centrifugal extrusion, spheronization, drum granulation and high shear agglomeration.

Abstract: A method for treating myocardium using at least one mechanical or electromagnetic energy functional device for forming a network of branched, interconnecting passages in a boundary between endocardium and myocardium, thereby enhancing blood flow into the treated zone, and a device for selectively treating ischemic myocardium tissue comprising a tube having proximal end and distal end, and at least one hollow lumen and defining an axis, at least two mechanical or electromagnetic energy functional devices disposed within the tube, the at least two mechanical or electromagnetic energy functional devices each having a distal end disposed adjacent the distal end of the central tube, and a deflecting member adjacent the distal portion of the central tube for deflecting the distal end of each of the at least two mechanical or electromagnetic energy functional devices away from the axis, for enabling treatment of selective areas of ischemic or hibernating myocardium tissue.

Abstract: An elongated steerable catheter for placement within a heart chamber, organ aperture or other body opening and having at least one center tube with hollow passageway for guiding a laser delivery means or other functional device to selected surfaces of a heart chamber, organ aperture or other body cavity for laser or other treatment thereon, particularly adapted for laser-assisted percutaneous transmyocardial revascularization (TMR), is disclosed herein. The steerable catheter has a handle portion at its proximal end and a controllably deflectable end portion at its distal end. The elongated center tube has a distal end, in the region where a curvature is to be formed, and a shim anchor sleeve is slidably disposed over the center tube. The shim anchor sleeve is attached to the inside wall of the outer jacket and coupled to the distal end of the center tube with a bendable shim member which extends between the distal tip of the steerable catheter and the sleeve over the center tube.

Abstract: An apparatus and method for creating drug-filled pockets within muscle tissue, such as myocardium of the heart for increasing angiogenesis. More particularly, the apparatus has an excising assembly with a dilator tip for penetrating and advancing through the surface and body of a muscle or organ, such as the heart. Preferably, the dilator tip has a low level laser optical fiber emission to ease the passage of the excising assembly and provide thermal damage which also stimulates angiogenesis. More preferably, the dilator tip also disperses a pharmacologically active substance as the apparatus is passed through the tissue and/or creates pockets. The excising assembly is connected to a hand-held control device from which the operator pushes a switch to activate a punching mechanism within the excising assembly. The punching mechanism cuts a discrete piece of muscle tissue and traps it within the excising assembly leaving a pocket in the remaining muscle tissue.

Abstract: A method of visualizing and treating the heart by providing a balloon end contact scope with a main lumen, an essentially transparent contact viewing portion, and integral laser delivery means or other equipment channel suitable for viewing the heart; precisely positioning the contact viewing portion in contact with a portion of the heart adjacent the position to be viewed; and visualizing the heart. The scope may have a gripping surface particularly suitable for percutaneous use. For MIS use, the scope tents the pericardial sac. The method can be used to place a guide wire or tether to the heart to locate a fluoroscopic or other visualization means or to perform additional visualization, fluoroscopic marking or other interventional procedures. The method also comprises the step of delivering laser energy to a portion of the heart to effect transmyocardial revascularization.

Abstract: A treatment tool such as a catheter, MIS or other surgical tool apparatus for placement within a heart chamber, organ aperture or other body opening and axial ranging therein, the apparatus particularly adapted for laser-assisted percutaneous transmyocardial revascularization (MTR). At the distal end of the tool is an annular ultrasound transducer with associated structure, positioned to transmit ultrasound signals substantially axially aligned with the axis of the treatment tool to the cardiovascular tissue, the transducer further receiving returning signals from the cardiovascular tissue to be treated. In a preferred embodiment, the transducer comprises a piezoelectric crystal material. The transducer assembly is attached to the distal tip of the tool such that a laser delivery means or other functional device can be extended through the lumen of the tool and the annular ultrasound transducer.

Abstract: A laser surgery device for performing laser myocardial revascularization procedures on a human heart comprises a hand-held body portion with a forwardly extending probe member with an enlarged head end assembly including a piercing tip. A movable fiber bundle connected to a laser source extends through the body portion and the probe member with its distal tip at the head end assembly. A control button on the body portion enables the device to move the distal tip forwardly from the head end, and selectable stop members are provided on the body portion to provide different travel distances for the optical fiber bundle during a procedure. The body portion has a rotatable nose-piece with an internal ratchet mechanism which enables the device user to rotate the probe member and its head end to a selected optimum position before commencing a procedure.

Abstract: A heart stabilizer and suture control device for stabilizing the heart and for occluding a preselected portion of coronary artery by developing a downward force on the heart and simultaneously developing an upward force across a coronary artery in a predetermined position. The device has at least two stabilization pads, the stabilization pads each having an operative size and shape, and each having a first end and a second end and a lower contacting surface. The second ends have suture retaining grooves, and the stabilization pad has a suture locking means for securing the distal end of a suture means thereto. The device also comprises a linking member locking the two stabilization pads an operative distance apart. The device has suture means with a proximal end coupled to the linking member and extending from the first end to the suture retaining groove of the second end, the suture means having a distal end which can be locked to the stabilization pad with the suture locking means thereon.

Abstract: A drug delivery apparatus for dispensing a predetermined amount of one or more drugs into a laser created opening in the human body, the apparatus consisting of a laser delivery means such as an optical fiber or fiber bundle, a drug conduit which transfers the one or more drugs, drug solutions or other substances to the distal end of the laser delivery means, and the laser delivery means disposed essentially coaxially with the drug conduit. Laser delivery means is used to create a TMR channel or other opening in the body. Dispensed drug or other substance travels through the drug conduit and emanates from the drug conduit to be delivered into the TMR channel or other laser created opening. Drug is dispensed by manually or automatically activating an electric motor which actuates a piston element. A method of use is also disclosed.

Abstract: An apparatus for creating revascularization channels in tissue, such as the myocardium of the heart, mechanically cuts the channels using a hand piece with easily removable cutting tip assemblies having angled, sharpened edges to allow rapid tip replacement. The cutting tip assembly has an inner needle within an outer hollow needle with each needle attached to the hand piece for independent rotation and axial movement. The inner needle may be hollow, or formed with a pointed tip, and may rotate counter to the outer needle to enhance gripping and storage of the tissue excised by the outer needle. The hand piece may attach a cylindrical magazine of cutting tip assemblies or one cutting tip assembly. The cutting tip assembly may be heated to provide thermal damage to the heart muscle during the creation of the channel, providing some of the advantages of the laser method of TMR.

Abstract: A semi-automatic cardiac tissue removal device for obtaining biopsy samples and/or creating revascularization pathways in the myocardium of the heart, mechanically cuts the pathways using a handpiece with a cutting tip assembly having a hollow needle with an angled, sharpened edge rotatable mounted around a separately advancable stylet. The stylet defines a piercer to spread the myocardium prior to insertion of the needle and to allow creation of a pathway only within the myocardium. The stylet further defines a plug at the cutting edge of the needle to finish the cutting cleanly and to plug the hollow needle thereby forming a closed chamber for excised tissue. A single button on the left or right handed handpiece actuates movement of the stylet into the myocardium, movement of the needle into the path produced by the piercer, and rotation of the needle to cut tissue.

Abstract: A drug delivery apparatus for dispensing predetermined volumes of drug, drug solution or other substances into an opening, such as a TMR channel in the human heart, or other laser treated area within the human body, the apparatus consisting of a bifurcated needle with a laser inlet for guiding a laser delivery means, such as an optical fiber or fiber bundle, to adjacent a surface of the human heart or other body structure for creating an opening, such as a TMR channel, or other laser treated area thereon. A drug inlet is for receiving the drug and transmitting the drug to the TMR channel or other laser treated area. Optionally, a piercing tip and/or suction device assists in positioning the apparatus adjacent the tissue to be treated. Drug is dispensed by manually or automatically actuating a piston or syringe element. A method of use is also disclosed.

Abstract: Improved methods and apparatuses related to laser-assisted intra-coronary transmyocardial revascularization (ITMR), and more particularly, to improved methods and apparatuses for directing an interventional catheter device, via percutaneous or other entry into the vasculature, for example at the femoral artery, over the aortic arch, through the ascending aorta and over the coronary ostia such that the laser delivery means can be positioned inside a coronary artery and laser energy is used to create a plurality of small channels through the coronary artery into the tissue of the myocardium. An proximal hub portion and method of using it are described, the proximal hub portion adapted for attachment to a central, elongated lumen portion, the proximal hub portion optionally having a plurality of branched extending arms, the sheath and associated branched arms having individual blood loss seals and individually capable of receiving a laser delivery means, visualization or marking means, or other tools.

Abstract: An elongated steerable catheter for placement within a heart chamber, organ aperture or other body opening and having at least one center tube with hollow passageway for guiding a laser delivery means or other functional device to selected surfaces of a heart chamber, organ aperture or other body cavity for laser or other treatment thereon, particularly adapted for laser-assisted percutaneous transmyocardial revascularization (TMR), is disclosed herein. The steerable catheter has a handle portion at its proximal end and a controllably deflectable end portion at its distal end. The elongated center tube has a distal end, in the region where a curvature is to be formed, and a shim anchor sleeve is slidably disposed over the center tube. The shim anchor sleeve is attached to the inside wall of the outer jacket and coupled to the distal end of the center tube with a bendable shim member which extends between the distal tip of the steerable catheter and the sleeve over the center tube.

Abstract: An apparatus for creating revascularization channels in tissue, such as the myocardium of the heart, mechanically cuts the channels using a hand piece with easily removable cutting tip assemblies having angled, sharpened edges to allow rapid tip replacement. The cutting tip assembly has an inner needle within an outer hollow needle with each needle attached to the hand piece for independent rotation and axial movement. The inner needle may be hollow, or formed with a pointed tip, and may rotate counter to the outer needle to enhance gripping and storage of the tissue excised by the outer needle. The hand piece may attach a cylindrical magazine of cutting tip assemblies or one cutting tip assembly. The cutting tip assembly may be heated to provide thermal damage to the heart muscle during the creation of the channel, providing some of the advantages of the laser method of TMR.

Abstract: A transmyocardial revascularization (TMR) enhanced treatment for coronary artery disease and other medical procedures utilizing a source of laser energy and a laser delivery means attached thereto, the treatment or other medical procedure being one in which the coronary artery is temporarily occluded during a surgical procedure, the enhanced treatment comprising the steps of positioning the laser delivery means adjacent the distal anatomy of the heart muscle, delivering laser energy to the distal anatomy of the heart muscle through the laser delivery means to create at least one TMR channel communicating oxygenated blood from the left ventricle to myocardium of the distal anatomy of the heart muscle, such that during treatment or other medical procedure in which the coronary artery is temporarily occluded, the distal anatomy of the heart is essentially continuously supplied with oxygenated blood, and performing the treatment or other medical procedure in which the coronary artery is temporarily occluded durin

Abstract: An apparatus for performing a laser myocardial revascularization of a human heart comprises a hand-held device with an elongated flexible lasing assembly including an axially movable fiber bundle which can be placed into the chest cavity of a patient. At the distal head end of the device laser energy from the distal end of the fiber bundle is initially reduced to form a relatively small opening in the epicardium of the heart. The fiber bundle is moved through the opening so that lasing with full laser power takes place beneath the epicardium to form a larger channel through the myocardium that extends into the left ventricular cavity. After the channel has been formed, the optical fiber bundle is retracted from the channel and back through the small epicardium opening so as to minimize operative bleeding and allow sealing of the epicardium after the apparatus is removed.