Patent EA-001146-B1 (EA)
Title: Method of treating a subject suffering from disease in the pathogenesis of which neovascularization of great importance
Inventor: GREEN LAWRENCE R
IPC: C07K5/072
Filed: 1996-10-02
Abstract: 1. A method of treating a subject in need thereof having a pathologic condition involving neovascularization comprising administering a pharmaceutical preparation R'-Glu-Trp-R" dipeptide or a pharmaceutically acceptable salt and a pharmaceutically acceptable carrier in an amount effective to inhibit neovascularization. 2. The method of claim 1 wherein the R'-Glu-Trp-R" dipeptide is Glu-L-Trp or a pharmaceutical salt Glu-L-Trp. 3. The method of claim 1 or 2 wherein the neovascularization results from an hemangioma. 4. The method of claim 1 or 2 wherein the neovascularization results from a vascularized malignant tumor or vascularized benign tumor. 5. The method of claim 1 or 2 wherein the neovascularization results from post-recovery cerebrovascular accident; head trauma; restenosis following angioplasty; or heat or cold trauma. 6. The method of claim 1 or 2 wherein neovascularization is associated with substance-induced neovascularization of the liver angiogenic dysfunction related to an excess of hormone; neovascular sequelae of diabetes; neovascular sequelae to hypertension; or chronic liver infection. 7. The method of claims 1 to 6 comprising administering to the subject a dose of of about 0.5 μg per 1 kilogram body weight to about 1 μg per 1 kilogram body weight. 8. The method of claims 1 to 7 wherein the effective amount is about 1 μg/kg to about 50 μg/kg body weight. 9. The method of claims 1 to 8 wherein the dose is administered daily over a period of 1 day to about 30 days. 10. The method of claims 1 to 9 wherein the pharmaceutical preparation is administered parentially, topically, subcutaneously, intermascularly, intrathecally, orally, intranasally, intraperitionelly or gastrointestinally. 11. The method of claims 1 to 10 comprising administering the pharmaceutical preparation in the form of an injectable solution. 12. The method of claims 1 to 10 comprising administering the preparation in a unit dose form comprising a tablet, a suppository, a capsule, an eye film, an inhalant, a mucosal spray, a nose drop, an eye drop, a toothpaste, an ointment, or water soluble based cream. 13. The method of claim 12 wherein said unit dose form consists essentially of 0.01 mg of the R'-Glu-Trp-R" dipeptide or a pharmaceutically acceptable salt thereof. 14. The method of claims 1 to 13 further comprising administering to the subject a vasoactive drug. 15. The method of claim 14 wherein the vasoactive drug is an angiotensin converting enzyme (ACE) inhibitor or a potassium channel opener (PCO). 16. The method of claims 4 to 14 wherein the subject suffers from a tumor and wherein the method further comprises administering a chemotherapeutic agent to the subject. 17. The method of claims 1 to 16 wherein the subject is not immune compromised. 18. The method of claim 4 wherein the tumor is a tumor of the meninges; an intracerebral tumor; a sarcoma; an osteosarcoma; a tumor of the esophagus; or a tumor of the trachea,. a tumor of Lewis carcinoma. 19. The method of claim 6 wherein the neovascular sequelae of diabetes is central serous chorioretinopathy. 20. The method of claims 1 to 19 wherein the subject is a mammal. 21. The method of claim 20 wherein a mammal is a human. 22. The method of treating a subject in need thereof having a pathologic condition involving neovascularization comprising administering a pharmaceutical preparation Glu-L-Trp dipeptide, a cyclic form of dipeptide, linear or cyclic dipeptide polymer, comprising not more than 20 amino acids, an analog of dipeptide in which the nitrogen in the pyrole ring of tryptophan is replaced with carbon, or a pharmaceutically acceptable salt and a pharmaceutically acceptable carrier in an amount effective to inhibit neovascularization. 23. The method of claims 1 to 22 wherein the pharmaceutically acceptable salt is selected from the group including sodium, potassium, ammonium or zink. 24. The method of claims 1 to 23 wherein the pharmaceutically acceptable salt is selected from the group which includes hydrochloride, hydrobromide, sulfate, bisulfate, acetate, oxalate, valarate, oleate, laurate, borate, benzoate lactate, phosphate, tosulate, citrate, maleate, fumarate, succinate or tartrate. 25. The method of claims 2 to 24 wherein Glu-L-Trp sodium salt is administered. 26. The method of claims 2 to 25 wherein Glu-L-Trp sodium salt is administered in the form of salt solution. 27. The method of claims 2 to 26 wherein Glu-L-Trp sodium salt is administered intranasally or by intrabronchial spraying. 28. The method of treating a subject in need thereof having a pathologic condition involving neovascularization comprising administering a pharmaceutical preparation R'-Glu-Trp-R" dipeptide or an analog thereof, in which he nitrogen in the pyrole ring of tryptophan is replaced with carbon, or a pharmaceutically acceptable salt and a pharmaceutically acceptable carrier in an amount effective to inhibit neovascularization. 29. The method of claim 28 wherein R'-Glu-Trp-R" dipeptide is Glu-L-Trp or an analog thereof, in which in which he nitrogen in the pyrole ring of tryptophan is replaced with carbon.