Formulations and methods for vascular permeability-related diseases or conditions

• US 20070265294A1
• Filed: 03/23/2007
• Published: 11/15/2007
• Est. Priority Date: 03/23/2006
• Status: Active Grant

• Current Assignee: Santen Pharmaceutical Company Limited
• Original Assignee: Santen Pharmaceutical Company Limited
• Inventors: Nivaggioli, Thierry, Weber, David, Gerritsen, Mary, Kleinman, David
• Granted Patent: US 8,222,271 B2
• Time in Patent Office: Days
• US Class Current: 514/291
• CPC Class Codes: A61K 31/436 the heterocyclic ring system containing a six-membered ring having oxygen as a ring hetero atom, e.g. rapamycin
• CPC Class Codes: A61K 47/10 Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 31/16 for influenza or rhinoviruses
• CPC Class Codes: A61P 39/02 Antidotes
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 7/10 Antioedematous agents; Diuretics
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis

Abstract

Described herein are formulations and methods for treating, inhibiting, preventing, delaying onset, or causing regression of a disease or condition relating to vascular permeability.

Claims

1. A method to treat, prevent, inhibit, delay onset of, or cause regression of a disease or condition comprising administering to a subject in need thereof an effective antipermeability amount of a therapeutic agent,

wherein the therapeutic agent is a limus compound or an analog, derivative, salt, or ester thereof,

and the disease or condition is selected from the group consisting of retinal edema, influenza, viral encephalitis, neuroretinitis, endotoxin induced edema, vasculitis, toxic metabolic brain edema, hemangiomas, von Hippel Lindau disease, angioneurotic edema, snake bite, high altitude cerebral edema (HACE), high altitude pulmonary edema (HAPE), pulmonary edema associated with smoke inhalation, pulmonary edema associated with anoxia, hyponatremic brain edema, edema associated with blunt trauma, brain edema following stroke or closed head injury, and corneal edema.

4. The method of any of claims 1-3, wherein the amount of the therapeutic agent administered results in a concentration of the therapeutic agent in a tissue associated with the disease or condition of no greater than an amount equivalent to 41 ng/g of rapamycin.

5. The method of any of claims 1-3, wherein the therapeutic agent is administered to the subject in need thereof at a dose of no greater than an amount equivalent to 2 mg/kg of rapamycin.

6. The method of any of claims 1-3, wherein the subject is a human subject.

7. The method of claim 6, wherein the disease or condition is any one or more of retinal edema, von Hippel Lindau disease, and corneal edema.

8. The method of claim 1, wherein the therapeutic agent is a limus compound or a pharmaceutically acceptable salt or ester thereof.

11. The method of claim 6, wherein the disease or condition is selected from the group consisting of macular edema, retinal edema, von Hippel Lindau disease, corneal edema, Vogt-Koyanagi-Harada disease, and exudative retinal detachment.

12. The method of claim 4, wherein amount of the therapeutic agent administered results in a concentration of the therapeutic agent in a tissue associated with the disease or condition of no greater than an amount equivalent to 11 ng/g rapamycin.

13. The method of claim 12, wherein amount of the therapeutic agent administered results in a concentration of the therapeutic agent in a tissue associated with the disease or condition of no greater than an amount equivalent to 7 ng/g of rapamycin.

16. The method of claim 5, wherein the subject is a human subject.

17. The method of claim 5, wherein the therapeutic agent is administered to the subject in need thereof at a dose of no greater than an amount equivalent to 0.5 mg/kg of rapamycin.

18. The method of claim 17, wherein the therapeutic agent is administered to the subject in need thereof at a dose of no greater than an amount equivalent to 0.27 mg/kg of rapamycin.

19. The method of claim 18, wherein the therapeutic agent is administered to the subject in need thereof at a dose of no greater than an amount equivalent to 0.07 mg/kg of rapamycin.

20. The method of claim 19, wherein the therapeutic agent is administered to the subject in need thereof at a dose of no greater than an amount equivalent to 0.014 mg/kg of rapamycin.

21. The method of claim 6, wherein the method is a method to treat the disease or condition.

23. The method of claim 6, wherein the method is a method to prevent the disease or condition.

25. The method of any of claims 1-3, wherein the thereapeutic agent is rapamycin, and the rapamycin is administered in a formulation containing about 2% w/w rapamycin, about 4% w/w ethanol, and about 94% w/w PEG 400.

27. The method of any of claims 1-3 or 26, wherein the subject is a human subject.

28. The method of claim 4, wherein the therapeutic agent is rapamycin and the subject is a human subject.

29. The method of claim 5, wherein the therapeutic agent is rapamycin and the subject is a human subject.

30. The method of claim 18, wherein the therapeutic agent is rapamycin and the subject is a human subject.

31. The method of claim 25, wherein the therapeutic agent is rapamycin and the subject is a human subject.

2. A method to treat, prevent, inhibit, delay onset of, or cause regression of a disease or condition comprising administering to a subject in need thereof an effective antipermeability amount of a therapeutic agent,

wherein the therapeutic agent is an immunophilin binding compound or an analog, derivative, salt, or ester thereof,

and the disease or condition is selected from the group consisting of retinal edema, influenza, viral encephalitis, neuroretinitis, endotoxin induced edema, vasculitis, toxic metabolic brain edema, hemangiomas, von Hippel Lindau disease, angioneurotic edema, snake bite, high altitude cerebral edema (HACE), high altitude pulmonary edema (HAPE), pulmonary edema associated with smoke inhalation, pulmonary edema associated with anoxia, hyponatremic brain edema, edema associated with blunt trauma, brain edema following stroke or closed head injury, and corneal edema.

9. The method of claim 2, wherein the therapeutic agent is an immunophilin binding compound or a pharmaceutically acceptable salt or ester thereof.

3. A method to treat, prevent, inhibit, delay onset of, or cause regression of a disease or condition comprising administering to a subject in need thereof an effective antipermeability amount of a therapeutic agent,

wherein the disease or condition is selected from the group consisting of retinal edema, influenza, viral encephalitis, neuroretinitis, endotoxin induced edema, vasculitis, toxic metabolic brain edema, hemangiomas, von Hippel Lindau disease, angioneurotic edema, snake bite, high altitude cerebral edema (HACE), high altitude pulmonary edema (HAPE), pulmonary edema associated with smoke inhalation, pulmonary edema associated with anoxia, hyponatremic brain edema, edema associated with blunt trauma, brain edema following stroke or closed head injury, and corneal edema,

and the therapeutic agent is selected from the group consisting of rapamycin, SDZ-RAD, tacrolimus, everolimus, pimecrolimus, CCI-779, AP23841, ABT-578, TAFA-93, RAD-001, temsirolimus, AP23573, 7-epi-rapamycin, 7-thiomethyl-rapamycin, 7-epi-trimethoxyphenyl-rapamycin, 7-epi-thiomethyl-rapamycin, 7-demethoxy-rapamycin, 32-demethoxy-rapamycin, 2-desmethyl-rapamycin, monoester derivatives of rapamycin, diester derivatives of rapamycin, 27-oximes of rapamycin;

42-oxo analogs of rapamycin;

bicyclic rapamycins;

rapamycin dimers;

silyl ethers of rapamycin;

rapamycin arylsulfonates, rapamycin sulfamates, monoesters at positions 31 and 42, diesters at positions 31 and 42, 30-demethoxy rapamycin, and pharmaceutically acceptable salts and esters thereof.

10. The method of claim 3, wherein the therapeutic agent is rapamycin or a pharmaceutically acceptable salt or ester thereof.

14. The method of claim 10, wherein the therapeutic agent is rapamycin.

15. The method of claim 3, wherein the therapeutic agent is selected from the group consisting of rapamycin, SDZ-RAD, tacrolimus, everolimus, pimecrolimus, CCI-779, AP23841, ABT-578, and pharmaceutically acceptable salts and esters thereof.

22. The method of claim 14, wherein the method is a method to treat the disease or condition.

24. The method of claim 14, wherein the method is a method to prevent the disease or condition.

26. A method to treat, prevent, inhibit, delay onset of, or cause regression of a disease or condition comprising administering to a subject in need thereof an effective antipermeability amount of a therapeutic agent,

wherein the therapeutic agent is a limus compound or an analog, derivative, salt, or ester thereof,

the therapeutic agent is administered to the subject in need thereof at a dose of no greater than an amount equivalent to 2 mg/kg of rapamycin,

and the disease or condition is selected from the group consisting of diabetic macular edema, cystoid macular edema, macular edema from vein occlusion, congestive heart failure, pulmonary edema, ARDS, asthma induced pulmonary edema, hemangioblastoma, pemphigous, tuberous sclerosis, edema secondary to bites or stings, Vogt-Koyanagi-Harada disease, scleritis, and exudative retinal detachment.