Methods for the treatment of nephro-disorders using aminothiol compounds

• US 6,586,476 B1
• Filed: 10/28/1999
• Issued: 07/01/2003
• Est. Priority Date: 12/09/1997
• Status: Expired due to Term

• Current Assignee: Clinigen Group PLC, Arizona Board of Regents (University of Arizona)
• Original Assignee: MedImmune Oncology, Inc. (Astrazeneca PLC)
• Inventors: Alberts, David S., Kaplan, Edward H., Stogniew, Martin
• Primary Examiner(s): TRAVERS, RUSSELL S
• Application Number:
  US09/429,290
• Time in Patent Office: 1,342 Days
• Field of Search: 514/114, 514/665, 514/649, 514/608, 514/706
• US Class Current: 514/665
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/13 Amines A61K31/04 takes precedence
• CPC Class Codes: A61K 31/135 having aromatic rings , e.g. ketamine, nortriptyline methadone A61K31/137
• CPC Class Codes: A61K 31/145 having sulfur, e.g. thiurams (>N—C(S)—S—C(S)—N< and >N—C(S)—S—S—C(S)—N<), Sulfinylamines (—N=SO), Sulfonylamines (—N=SO2) isothiourea A61K31/155
• CPC Class Codes: A61K 31/16 Amides, e.g. hydroxamic acids
• CPC Class Codes: A61K 31/195 having an amino group
• CPC Class Codes: A61K 31/426 1,3-Thiazoles
• CPC Class Codes: A61K 31/66 Phosphorus compounds
• CPC Class Codes: A61K 31/661 Phosphorus acids or esters thereof not having P—C bonds, e.g. fosfosal, dichlorvos, malathion or mevinphos
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 1/02 Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 15/08 for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
• CPC Class Codes: A61P 17/14 for baldness or alopecia
• CPC Class Codes: A61P 17/16 Emollients or protectives, e.g. against radiation
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 21/00 Drugs for disorders of the muscular or neuromuscular system
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/02 for peripheral neuropathies
• CPC Class Codes: A61P 27/16 : Otologicals
• 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 31/04 : Antibacterial agents
• CPC Class Codes: A61P 31/12 : Antivirals
• CPC Class Codes: A61P 35/00 : Antineoplastic agents
• 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 9/10 : for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis

Abstract

The present invention relates to new uses of S-2-(3-aminopropylamino)ethyl dihydrogen phosphorothioate, (amifostine) and other aminothiol compounds to treat and reverse toxicities caused by therapeutic agents, radiation treatment or diabetes. In particular, the invention provides a method for treating neurotoxicity and nephrotoxicity associated with the administration of chemotherapeutic agents.

Claims

1. A method for treating a nephro-disorders in a human which comprises administering a therapeutically effective amount of one or more aminothiol compounds, or a pharmaceutically acceptable salt thereof, to a human in need of such treatment after the occurrence of said nephro-disorders.

2. The method of claim 1, wherein said nephro-disorder is chemically induced, drug induced, induced by aging, induced by exposure to radiation, induced by diabetes or induced by an unknown etiology.

3. The method of claim 2 wherein said nephro-disorder is induced by diabetes.

4. The method of claim 1, wherein said nephro-disorder is a nephrotoxicity associated with the administration of radiation therapy of one or more therapeutic agent(s).

5. The method of claim 1 wherein said nephro-disorder is characterized by elevations in BUN, serum creatinine, or a decrease in creatinine clearance or sodium magnesium or a combination thereof.

6. The method of claim 4 wherein said therapeutic agent is an antiviral, an antibiotic, an antifungal, a contrast agent or a combination thereof.

7. The method of claim 1 wherein said nephro-disorder is a result of the administration of cisplatin, carboplatin, pactitaxel, docetaxel, vincristine, navelbine, gemcytobin, etoposide, doxorubicin, daunorubicin or a combination thereof.

8. The method of claim 1 wherein said nephro-disorder is a result of the administration of 3′

-azido-3′

-deoxythymidine (AZT), d4T (stavadine), ddI (didanosine), ddC (zalcitabine), 3TC (lamivudine), gentamicin, tobramicin, kanamicin, amikacin, vancamicin, amphotericin B or a combination thereof.

9. The method of claim 1, wherein said aminothiol compound is administered intravenously, subcutaneously, intramuscularly, intradermally, topically or orally.

10. The method of claim 1 wherein said human is a cancer patient, AIDS patient, diabetic, or hypertensive patient.

11. The method of claim 1 wherein said aminothiol compound is a compound of the formula:

12. The method of claim 11, wherein said compound is selected from the group consisting of WR-1065, WR-151326, WR-151327, WR-638, WR-3689, WR-2822, WR-2529, WR-77913, WR-255591, WR-2823, WR-255709 and salts or hydrates thereof.

13. The method of claim 1, wherein said aminothiol is amifostine.

14. The method of claim 1, wherein said aminothiol is WR-33278.

15. The method of claim 1, wherein said aminothiol is an active metabolite of WR-2721.

16. The method of claim 1, wherein said aminothiol is a prodrug of an active metabolite of WR-2721.

17. The method of claim 1, wherein said aminothiol is administered one or more days after the occurrence of said nephro-disorders.

18. The method of claim 1, wherein two or more aminothiol compounds are administered.

19. The method of claim 1, wherein the amount administered is from about 10 mg/m² to about 2,000 mg/m².