Intracorporeal medicaments for photodynamic treatment of disease

Abstract

New intracorporeal photodynamic medicaments and certain medical uses and methods for use of such photodynamic medicaments for treatment of disease in human or animal tissue are described, wherein a primary active component of such medicaments is a halogenated xanthene or halogenated xanthene derivative. In preferred embodiments, such medicaments are used for treatment of a variety of conditions affecting the skin and related organs, the mouth and digestive tract and related organs, the urinary and reproductive tracts and related organs, the respiratory tract and related organs, the circulatory system and related organs, the head and neck, the endocrine and lymphoreticular systems and related organs, various other tissues, such as connective tissues and various tissue surfaces exposed during surgery, as well as various tissues exhibiting microbial or parasitic infection. In another preferred embodiment, such medicaments are produced in various formulations including liquid, semisolid, solid or aerosol delivery vehicles.

1 - 44 . (canceled)  
     
     
         45 . An intracorporeal photodynamic medicament, the medicament consisting of an aqueous solution of a sodium, potassium or lithium salt of a halogenated xanthene, wherein said halogenated xanthene is a compound selected from the group consisting of Dibromofluorescein, Solvent Red 72, Erythrosin B, Phloxine B, and Rose Bengal, and wherein said medicament includes directions for usage as an intracorporeal medicament for photodynamic treatment, using activating light having an intensity of less than 1 W/cm 2 , of human tissue.  
     
     
         46 . The medicament of  claim 45  wherein said halogenated xanthene is present in said medicament in a concentration of greater than 0.001% weight/volume (W/V) to less than 20% weight/volume (W/V).  
     
     
         47 . The medicament of  claim 45  wherein said halogenated xanthene is Rose Bengal.  
     
     
         48 . The medicament of  claim 45  further comprising at least one targeting moiety coupled to said halogenated xanthene.  
     
     
         49 . The medicament of  claim 48  wherein said targeting moiety is selected from the group consisting of deoxyribonucleic acid (DNA), ribonucleic acid (RNA), amino acids, proteins, antibodies, ligands, haptens, carbohydrate receptors, carbohydrate complexing agents, lipid receptors, lipid complexing agents, protein receptors, protein complexing agents, chelators, encapsulating vehicles, short-chain aliphatic hydrocarbons, long-chain aliphatic hydrocarbons, aromatic hydrocarbons, aldehydes, ketones, alcohols, esters, amides, amines, nitrites, azides, hydrophilic moieties and hydrophobic moieties.  
     
     
         50 . The medicament of  claim 45  wherein said aqueous solution includes one or more adjuvants selected from the group consisting of builders, stabilizers, emulsifiers, dispersants, preservatives, buffers, and electrolytes.  
     
     
         51 . The medicament of  claim 45  wherein said medicament is for the treatment of indications selected from the group consisting of conditions affecting the skin and related organs, conditions affecting the mouth and digestive tract and related organs, conditions affecting the urinary and reproductive tracts and related organs, conditions affecting the respiratory tract and related organs, conditions affecting the circulatory system and related organs, conditions affecting the head and neck, conditions affecting the endocrine and lymphoreticular systems and related organs, conditions affecting connective tissues, conditions affecting tissue surfaces exposed during surgery, and conditions related to microbial, viral, fungal, and parasitic infection.  
     
     
         52 . The medicament of  claim 45  wherein said medicament is for photodynamic treatment using activating light having a wavelength of between approximately 500 nm and 600 nm.  
     
     
         53 . The medicament of  claim 45  wherein said intracorporeal administration comprises a route of administration selected from intravenous injection, intraperitoneal injection, intramuscular injection, intracranial injection, intratumoral injection, intraepithelial injection, transcutaneous delivery, per oesophageal administration, intraabdominal administration, intraapendicular administration, intraarterial administration, intraarticular administration, intrabronchial administration, intrabuccal administration, intracapsular administration, intracardial administration, intracartilaginous administration, intracavitary administration, intracephalic administration, intracolic administration, intracutaneous administration, intracystic administration, intradermal administration, intraductal administration, intraduodenal administration, intrafascicular administration, intrafat administration, intrafilar administration, intrafissural administration, intragastric administration, intraglandular administration, intrahepatic administration, intraintestinal administration, intralamellar administration, intralesional administration, intraligamentous administration, intralingual administration, intramammary administration, intramedullary administration, intrameningeal administration, intramyocardial administration, intranasal administration, intraocular administration, intraoperative administration, intraoral administration, intraosseous administration, intraovarian administration, intrapancreatic administration, intraparietal administration, intrapelvic administration, intrapericardial administration, intraperineal administration, intraperitoneal administration, intraplacental administration, intrapleural administration, intrapontine administration, intraprostatic administration, intrapulmonary administration, intrarachidian administration, intrarectal administration, intrarenal administration, intrascleral administration, intrascrotal administration, intrasegmental administration, intrasellar administration, intraspinal administration, intrasplenic administration, intrasternal administration, intrastromal administration, intrasynovial administration, intratarsal administration, intratesticular administration, intrathoracic administration, intratonsillar administration, intratracheal administration, intratubal administration, intratympanic administration, intraureteral administration, intraurethral administration, intrauterine administration, intravaginal administration, intravascular administration, intraventricular administration, intravertebral administration, intravesical administration, and intravitreous administration.  
     
     
         54 . A photodynamic pharmaceutical composition for intracorporeal administration consisting of an aqueous solution of a sodium, potassium or lithium salt of a halogenated xanthene, wherein said halogenated xanthene is a compound selected from the group consisting of Dibromofluorescein, Solvent Red 72, Erythrosin B, Phloxine B, and Rose Bengal, and wherein said pharmaceutical composition includes directions for usage as an intracorporeal pharmaceutical composition for photodynamic treatment using activating light having an intensity of less than 1 W/cm 2 .  
     
     
         55 . The pharmaceutical composition of  claim 54  wherein said halogenated xanthene is present in said composition in a concentration of greater than 0.001% weight/volume (W/V) to less than 20% weight/volume (W/V).  
     
     
         56 . The pharmaceutical composition of  claim 54  wherein said halogenated xanthene is Rose Bengal.  
     
     
         57 . The pharmaceutical composition of  claim 54  wherein said halogenated xanthene is 4,5,6,7-Tetrabromoerythrosin.  
     
     
         58 . The pharmaceutical composition of  claim 54  further comprising at least one targeting moiety coupled to said halogenated xanthene.  
     
     
         59 . The pharmaceutical composition of  claim 58  wherein said targeting moiety is selected from the group consisting of deoxyribonucleic acid (DNA), ribonucleic acid (RNA), amino acids, proteins, antibodies, ligands, haptens, carbohydrate receptors, carbohydrate complexing agents, lipid receptors, lipid complexing agents, protein receptors, protein complexing agents, chelators, encapsulating vehicles, short-chain aliphatic hydrocarbons, long-chain aliphatic hydrocarbons, aromatic hydrocarbons, aldehydes, ketones, alcohols, esters, amides, amines, nitrites, azides, hydrophilic moieties and hydrophobic moieties.  
     
     
         60 . The pharmaceutical composition of  claim 54  wherein said aqueous solution includes one or more adjuvants selected from the group consisting of builders, stabilizers, emulsifiers, dispersants, preservatives, buffers, and electrolytes.  
     
     
         61 . The pharmaceutical composition of  claim 54  wherein said pharmaceutical composition is activated using light having a wavelength of between approximately 500 nm and 600 nm.  
     
     
         62 . An intracorporeally-applicable photodynarnic medicament consisting of a sodium, potassium or lithium salt of a halogenated xanthene as the photoactive component formulated as an injectable aqueous solution, wherein said halogenated xanthene is a compound selected from the group consisting of Dibromofluorescein, Solvent Red 72, Erythrosin B, Phloxine B, and Rose Bengal, and wherein said medicament includes directions for usage as an intracorporeal medicament for photodynamic treatment.  
     
     
         63 . An intracorporeally-applicable photodynamic medicament consisting of an aqueous solution of a halogenated xanthene as the active component, wherein said halogenated xanthene is a compound selected from the group consisting of Dibromofluorescein, Solvent Red 72, Erythrosin B, Phloxine B, and Rose Bengal, and wherein such medicament includes directions for usage as an intracorporeal medicament for photodynaminc treatment of indications selected from the group consisting of conditions affecting the skin and related organs, conditions affecting the mouth and digestive tract and related organs, conditions affecting the urinary and reproductive tracts and related organs, conditions affecting the respiratory tract and related organs, conditions affecting the circulatory system and related organs, conditions affecting the head and neck, conditions affecting the endocrine and lymphoreticular systems and related organs, conditions affecting connective tissues, conditions affecting tissue surfaces exposed during surgery, or conditions related to microbial, viral, fungal, and parasitic infection.  
     
     
         64 . An intracorporeal photodynamic medicament, the medicament consisting of a halogenated xanthene formulated in a delivery vehicle selected from the group consisting of a tablet, a capsule, a suppository, a syrup, and a micro-droplet spray, wherein said halogenated xanthene is a compound selected from the group consisting of Dibromofluorescein, Solvent Red 72, Erythrosin B, Phloxine B, and Rose Bengal, and wherein said medicament includes directions for usage for photodynamic treatment, using activating light having an intensity of less than 1 W/cm 2 , of human tissue.  
     
     
         65 . A photodynamic pharmaceutical composition for intracorporeal administration consisting of a sodium, potassium or lithium salt of a halogenated xanthene formulated in a delivery vehicle selected from the group consisting of a tablet, a capsule, a suppository, a syrup, and a micro-droplet spray, wherein said halogenated xanthene is a compound selected from the group consisting of Dibromofluorescein, Solvent Red 72, Erythrosin B, Phloxine B, and Rose Bengal, and wherein said pharmaceutical composition includes directions for usage for photodynamic therapy.  
     
     
         66 . An intracorporeally-applicable photodynamic medicament consisting of a halogenated xanthene as the photoactive component, wherein said halogenated xanthene is a compound selected from the group consisting of Dibromofluorescein, Solvent Red 72, Erythrosin B, Phloxine B, and Rose Bengal, said medicament formulated as a tablet, a capsule, a suppository, a syrup or a micro-droplet spray, and wherein said medicament includes directions for usage for intracorporeal use in photodynamic treatment, using activating light having an intensity of less than 1 W/cm 2 , of human tissue.  
     
     
         67 . An intracorporeally-applicable photodynamic medicament consisting of a halogenated xanthene formulated in a delivery vehicle selected from the group consisting of a tablet, a capsule, a suppository, a syrup and a micro-droplet spray, wherein said halogenated xanthene is a compound selected from the group consisting of Dibromofluorescein, Solvent Red 72, Erythrosin B, Phloxine B, and Rose Bengal, and wherein such medicament includes directions for usage for photodynaminc treatment of indications selected from the group consisting of conditions affecting the skin and related organs, conditions affecting the mouth and digestive tract and related organs, conditions affecting the urinary and reproductive tracts and related organs, conditions affecting the respiratory tract and related organs, conditions affecting the circulatory system and related organs, conditions affecting the head and neck, conditions affecting the endocrine and lymphoreticular systems and related organs, conditions affecting connective tissues, conditions affecting tissue surfaces exposed during surgery, or conditions related to microbial, viral, fungal, and parasitic infection.