Surgery – Means for introducing or removing material from body for... – Treating material introduced into or removed from body...
Patent
1990-04-02
1991-10-01
Rosenbaum, C. Fred
Surgery
Means for introducing or removing material from body for...
Treating material introduced into or removed from body...
606 2, 128395, 128898, A61M 3100
Patent
active
050530062
DESCRIPTION:
BRIEF SUMMARY
ilar considerations may apply in the case of retinal neovasculature, such as occurs in diabetic retinopathy.
The photochemical interaction between intravenously injected rose bengal dye and light at a wavelength sufficient to electronically excite the rose bengal molecules can be used to initiate permanent thrombotic occlusion in the corneal neovasculature of rabbit eyes with experimentally induced lipid keratopathy. The photothrombotic procedure does not produce corneal edema or polymorphonuclear leukocyte infiltration, as has been found in studies employing laser-induced photocoagulation. Thus, the formation of additional neovascularization and lipid deposition, which takes place with photocoagulation, is avoided.
Potential uses for the photothrombotic method include injuring cells other than vascular endothelium, for example, tumor cells, e.g., highly vascularized skin tumors or in Greene's ocular melanoma. Occlusion of the feeding vessels would facilitate ischemic necrosis and consequent sloughing away of the tumor mass. This would be much preferred to surgery, in which case a large wound area is created. Another difficult problem is internal bleeding from the liver, which is difficult to stanch surgically. The presently disclosed photochemical method could be used to seal the bleeding blood vessel ends thrombotically by areal irradiation, without introducing the complications of thermal injury to functioning tissue.
As an extension of the principle of photochemically induced damage to endothelium, a photosensitizing dye could be attached to an isothiocyanate group, which itself can be complexed to a monoclonal antibody. This would make possible the localization of damage to specific molecular sites in a membrane.
Owing to steric hindrance, rose bengal cannot bind to an isothiocyanate group. However, the closely related dye, erythrosin B (mentioned above), can bind to isothiocyanate, and the resultant compound is commercially available.
The present inventor has attached erythrosin B to an endothelial antibody. Erythrosin B alone has been administered intravenously by the inventor to photothrombotically occlude the rat middle cerebral artery in the same fashion as rose bengal.
SUMMARY OF THE INVENTION
The present invention is directed to a method of inducing the permanent occlusion of arteries. According to this method, the absorption by systemically injected rose bengal dye of light at a wavelength sufficient to electronically excite the rose bengal molecules initiates singlet-oxygen motivated photochemical injury to the vascular endothelium. These luminal alterations stimulate intense platelet adherence and physiological aggregation, which leads to total occlusion of the artery at the point of interaction of the rose bengal dye and the light beam, which is preferably a laser light beam.
DETAILED DESCRIPTION OF THE INVENTION
The present invention is directed to a method for inducing the complete occlusion of arteries. The method utilizes an intravascular photochemical reaction to induce structural damage to normally non-thrombogenic vascular endothelium. The photochemical process is mediated by rose bengal, a potent photosensitizing dye injected into the bloodstream. Absorption by the injected rose bengal dye of light at a wavelength sufficient to electronically excite the rose bengal molecules induces photochemical injury via singlet oxygen peroxidation reactions in the vascular endothelium at the point of interaction of the rose bengal and the light beam, which is preferably a laser light beam.
Because wavelengths in the range of 510 nm to 580 nm are readily absorbed by rose bengal, and laser beams, for example, are easily focused, the rose bengal-sensitized photochemical reaction can be made sufficiently intense to stimulate platelet adhesion and aggregation even in high-flow vessels. In large arteries, the thrombus is a mixed aggregate of platelets, red blood cells and coagulum in the irradiated arterial segment; distally the thrombus consists of coagulated red blood cells. In small arteries,
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This invention was made with Government support under the National Institutes of Health research grant No. 1 RO1 NS-23244. The Government has certain rights in this invention.
This is a continuation-in-part (CIP) continuation of application Ser. No. 07/183,046, filed Apr. 19, 1988, which was abandoned upon the filing hereof 07/503,130.
Daley Kathleen A.
Rosenbaum C. Fred
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