Abstract: Connectors for optically coupling radiation accurately from radiation sources into waveguides in medical applications are provided. A preferred embodiment for coupling laser sources into optical fibers provides a connector comprising an outer body for handling connector; a two-part ferrule; an inner body which protects ferrule and holds its two parts together; a collet chuck through which an optical fiber is introduced; a spring; a ferrule interlock; and bending protection with a long fiber protection end. Main features are that the inner body moves within the outer body longitudinally, the spring-loaded ferrules move against a fixed position element in the laser housing via the spring load, and their relative shapes are designed to be assembled in only one possible angle position, thus maintaining alignment of elements to reduce/avoid lost power absorbed by the connector's proximal end due to coupling. The ferrule is mounted inside the connector and does not emerge from it for protecting the ferrule.

Abstract: Methods and devices to eliminate, reduce, destroy and/or inhibit undesired body fluid species, such as pathogen microbes and deteriorated or malignant cells in complex environments like blood, serum and other body fluids are provided. In preferred embodiments, an antimicrobial photodynamic therapy (PDT) treatment is given that effectively inactivates, reduces and/or destroys both Gram (?) and Gram (+) bacteria in complex body fluids. Methods to enhance antimicrobial PDT activity include administering a photosensitizer to bacteria-contaminated fluid, after a dwell time guiding bacteria-contaminated fluid with photosensitizer through a channel, emitting radiation preferably in an intermittent manner, and restoring treated body fluids to corresponding body regions. Electromagnetic radiation is preferably delivered intermittently with pulse width based on treatment parameters.

Abstract: Biologically active compounds are provided that can be used as photosensitizers for diagnostic and therapeutic applications, particularly for PDT of cancer, infections and other hyperproliferative diseases, fluorescence diagnosis and PDT treatment of a non-tumorous indication such as arthritis, inflammatory diseases, viral or bacterial infections, dermatological, ophthalmological or urological disorders as well as providing methods to obtain them in pharmaceutical quality. One embodiment consists of a method to synthesize a porphyrin with a defined arrangement of meso-substituents and then converting this porphyrin system to a chlorin system by dihydroxylation or reduction, and if more than one isomer is formed separate them by chromatography either on normal or reversed phase silica. In another embodiment the substituents on the porphyrin are selected to direct the reduction or dihydroxylation to the chlorin so that a certain isomer is selectively formed.

Abstract: Antimicrobial molecular conjugates for the treatment and prevention of infectious diseases caused by pathogenic microorganisms in human and animals are provided.

Abstract: Antimicrobial molecular conjugates for the treatment and prevention of infectious diseases caused by pathogenic microorganisms in human and animals are provided. The key to these conjugates is a special spacer connecting at least one photosensitizer to a microorganism receptor (vector) which in turn binds selectively to the surface of a microorganism bringing about photo-destruction upon irradiation. Spacers having hydrophilic structure such as ethylene glycol units and amino carboxyl end capped ethylene glycol units must be used for linking the vector to the photosensitizer. In a preferred embodiment a spacer would have at least 3 ethylene glycol units and be end capped with a carboxyl group on one end and a amino group at the other end. The present invention effectively works to combat bacterial infection in the real patient-related environments where blood, serum and other body fluids are always present or at least nearby.

Abstract: Compositions, which are stable in storage, and a method of production of pharmaceutical based nanoparticulate formulations for photodynamic therapy comprising a hydrophobic photosensitizer, human serum albumin (HSA) and stabilizing agent are provided. These nanoparticulate formulations provide therapeutically effective amounts of photosensitizer (PS) for parenteral administration. In particular, tetrapyrrole derivatives can be used as photosensitizers whose efficacy and safety are enhanced by such nanoparticulate formulations. A method of preparing the HSA-based nanoparticles under sterile conditions is also provided. In one of the preferred embodiments of the present invention temoporfin, a hydrophobic PS, is formulated as a nanoparticle for parenteral administration. The formulations are useful for treating hyperplasic and neoplasic conditions, inflammatory problems, and more specifically to target tumor cells.

Abstract: The present invention provides biologically active compounds that can be used as photosensitizers for diagnostic and therapeutic applications, particularly for PDT of cancer, infections and other hyperproliferative diseases, fluorescence diagnosis and PdT treatment of a non-tumorous indication such as arthritis, inflammatory diseases, viral or bacterial infections, dermatological, ophthalmological or urological disorders.

Abstract: A device and method for endovascular radiation therapy that prevents unwanted damage to blood vessels during treatment is described. The device is adapted to prevent the emission end of an energy delivery device from coming into contact with the wall of a blood vessel. The device is also adapted to sense the inputted radiation power and prevent irradiation above a preselected power or energy level. Both features serve to prevent radiation, having an overly high intensity or power density, from impacting the vessel wall and causing a puncture.

Abstract: Methods and devices are provided for efficient low power density endoluminal treatment of veins. Devices emit energy radially from an optical fiber with two or more emitting portions at its distal region. for 360° radial (circumferential) emission of vein walls. Emitting sections comprise a fiber with a truncated cone attached to a short conically-tipped fiber at the distal end. The fiber segments are butt-coupled or glued, and then laterally fused to the protective glass dome/cap. Laser power is substantially entirely absorbed within a fraction of the blood vessel wall to achieve blood vessel closure. Wavelengths including 980 nm, 1470 nm and 1950 nm are used which are substantially absorbed within the first third of a blood vessel wall. Consequently, a local anesthetic along the treated blood vessel is substantially avoided. Due to a fiber device's multiple emission points, withdrawal speed can be increased, and/or emitted energy levels can be set at minimum values.

Abstract: A special photosensitizer formulation and Photodynamic Therapy method for treating choroidal neovascularization (CNV) associated with age-related macular degeneration (AMD) is provided. CNV is a major cause for vision loss in elderly patients. A special drug delivery formulation is used to encapsulate the hydrophobic photosensitizer, preferably a pegylated liposome. This improves the solubility and therapeutic index of the photosensitizers. In one preferred embodiment, a pegylated photoactive agent remains confined in the intravascular compartment of neovasculature for a longer duration. Thus efficient elimination of neovascular proliferation and minimal damage to extravascular tissue and normal vessels is ensured. In this method, a hydrophobic photosensitizer, that is able to photochemically destroy neovessels, is injected into the patient. CNV irradiation with a non-thermal laser follows after a predefined time interval.

Abstract: Dynamic colorectal PDT methods, devices and photosensitizer compositions to treat abnormal cell growth in anal tissue such as perianal and intra-anal intraepithelial neoplasia grade III are presented. Dynamic colorectal PDT method comprises the steps of administering topically, intravenously or orally a photosensitizer composition; irradiating; monitoring treatment parameters before, during and/or after irradiation. Photosensitizer composition comprises Temoporfin and excipients/carriers, appropriate for the application method. An applicator is provided for colorectal PDT treatments enhancing irradiation delivery and monitoring treatment parameters. Preferably, applicator is made of a material, used to monitor the fluence rate simultaneously while doing optical spectroscopy. Measurement probe devices are provided for monitoring PDT treatment parameters in-vivo.

Abstract: A minimally invasive method for treating varices in especially sensitive areas, including pelvic varices in females, varicoceles, and also oesophageal varices is presented. The method comprises the steps of making a micro incision into the blood vessels of a patient, endoscopically inserting a catheter device into the blood vessel of a patient and advancing the distal end of the catheter to reach the varix or varices. For treatment of male varicocele, insertion is preferably made directly at the testicle. Alternatively, insertion can be made in the femoral vein and advanced using a catheter. Preferably, x-ray, angiography, or other imaging techniques are used to visualize and position the catheter. An optical fiber is then inserted into the catheter and the distal end is advanced to a predetermined point near the varix or varices. Optical fiber distal end is preferably a slim, radial 360 degree emitting fiber end.

Abstract: Innovative non-surgical methods and compositions are provided for administering PDT to promote tissue regeneration or augmentation while minimizing scarring and risk of infection. Among several areas of application, is the treatment of acute and chronic wounds which have afflicted epidermal and connective tissue layers of the body. Another application area is as cosmetic surgery/treatments, including: reducing wrinkles, sulcus, scars (acne or traumatic caused), sequelae cellulite, as well as for other skin irregularities, to give a smoother skin surface. This invention consists of a collagen based or other suitable biodegradable supporting matrix which is embedded with a liposomal loaded photosensitizer. In one embodiment of this invention a liposomal formulated photosensitizer is first injected at the site followed by collagen implantation and PDT treatment. In another embodiment a liposomal formulated photosensitizer is incorporated in the collagen.

Abstract: A method and a device for minimally invasive treatment of diseased deep and superficial venous valves are disclosed. Treatment seeks to repair/rejuvenate dysfunctional valve by reducing the circumference of dilated valve rings and by restoring their original shape and function using laser energy to make physical suture points and shrink collagen in selected points. Real time monitoring is by angioscopic view and endovenous echographic control. In a preferred embodiment, system comprises a specific catheter-like device for endovenous insertion that allows for real time view of energy emission and venous surface to be corrected. Catheter flexibility is such that viewing angle and direct energy emission can be oriented properly. Catheter can comprise channels for irrigation or for interchange of laser fibers according to desired irradiation pattern. A preferred embodiment of catheter device also comprises cuffs for temporary occlusion, by inflation and deflation.

Abstract: Pharmaceutical pegylated liposomal formulations for photodynamic therapy are presented. The pegylated liposomal formulation provides therapeutically effective amounts of the photosensitizer for intravenous administration. At least one of the phospholipids in the liposomes has been linked with poly ethylene glycol (PEG) as an integral part of the phospholipids. The formed pegylated liposomes contain the hydrophobic photosensitizer within the lipid bilayer membrane. Pegylation of liposomes carrying the hydrophobic photosensitizer helps to maintain the drug level within the therapeutic window for longer time periods and provides the drug a longer circulating half life in vivo. Further the pegylated formulation of hydrophobic photosensitizers shows improved pharmacokinetics over standard non-liposomal formulations thus enhancing the efficacy of PDT with the pegylated liposomal formulations.

Abstract: An improved system for safe and efficient generation of plasmas and vapors bubbles with continuous wave radiations and low levels of power densities, sufficient to treat medical pathologies and to avoid the creation damage to healthy tissue is provided. Transmission means in different configurations are used to achieve a high absorption in water, which is able to initiate plasma with low levels of power density. Once plasma and vapor bubbles are formed, they absorb other wavelengths in addition to the one that initiated it. Other wavelengths, more efficiently generated by diodes or diode pumped lasers, are added into the beam to improve treatment efficiency. This modulated plasma produces fast tissue ablation and good hemostasis effect with minimal overheating of remaining tissue. After plasma and high-energy vapors are generated, only laser radiation that passes through the plasma bubble directly interacts with soft tissues.

Abstract: A method and device for cosmetic surgery, especially fat reduction and collagen reformation, by means of a high power laser operating at about 980 nm is presented. The cosmetic surgery method substantially reduces or removes localized lipodystrophies, and essentially reduces flaccidity by localized laser heating of adipose tissue using an optical fiber inserted into a treatment area. The method and device are particularly well suited for treating Lipodystrophies with flaccidity High power laser energy is applied to “fat” cells to breakdown the cell walls releasing the cell fluid. The laser radiation is applied through an optical fiber which is held within a catheter-like device having a single lumen. Traditionally difficult fat cells are treated well. Delicate areas are treated safely. A saline solution may also be inserted into the treatment site to aid in the heating of the fat cells and their eventual destruction as well as their removal.

Abstract: Devices and transdermal methods are provided for safe and effective therapeutic treatment of the venous system, such as varicose veins. Present invention provides non-invasive and minimally invasive transdermal methods for treating varicose and spider veins, comprising the use of a radiation source in combination with a chemical fluid/composition to safely and more effectively close or shrink vein walls, providing a transdermal therapeutic method for varicose veins until now only treated with surgery or endovascular laser treatments. In a preferred embodiment a device comprises a radiation source, preferably of wavelength between about 980 and 1940 nm, being effective in causing shrinkage of the vein treated.

Abstract: An improved method and device for safe and efficient medical applications is provided. In a preferred embodiment, based on using the inherent benefits of laser diodes (such as efficient power generation from a reliable and compact solid state device), plasmas and high energy vapors are produced for medical applications with power levels and power densities sufficient to treat medical indications and avoid the creation of extensive damage zones. Transmissions means in different configurations are used to achieve a high power density, which is able to initiate plasma and high-energy vapor at the tip. Once a sparkless plasma and high energy vapor bubbles are formed, it is often found that it will also absorb other wavelengths in addition to the one that initiated it. As a consequence, other wavelengths more efficiently generated by diodes or diode pumped lasers may be added into the beam in order to improve treatment efficiency.

Abstract: A device and method are provided which achieve tissue ablation as well as tissue coagulation substantially simultaneously during the treatment of BPH by utilizing at least two wavelengths of light. The device and method improve urinary flow and minimize post-treatment blood loss and edema while maintaining a nearly blood-free operating field during treatment by irradiating substantially simultaneously with at least two different wavelengths of light. According to the present invention, tissue ablation is affected by having one wavelength that is highly absorbed in the prostatic tissue while another less highly absorbed wavelength coagulates surrounding tissues while maintaining minimal thermal damage to surrounding tissue. In a preferred embodiment the highly absorbed wavelength is about 1460 nm and the less absorbed by water but with some significant hemoglobin absorption is about 980 nm. This combination aids the patient by reducing blood loss and edema.