Use of taurolidine to treat tumors

• US 6,429,224 B1
• Filed: 12/06/2000
• Issued: 08/06/2002
• Est. Priority Date: 12/06/1999
• Status: Expired due to Term

• Current Assignee: Geistlich Pharma AG
• Original Assignee: Rhode Island Hospital
• Inventors: Darnowski, James, Calabresi, Paul
• Primary Examiner(s): Dees, Jose′ G.
• Assistant Examiner(s): Haghighatian, Mina
• Application Number:
  US09/730,923
• Publication Number:
  US 20020111345A1
• Time in Patent Office: 608 Days
• Field of Search: 514/222, 514/56, 514/538, 514/422
• US Class Current: 514/422
• 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 31/00 Medicinal preparations containing organic active ingredients
• CPC Class Codes: A61K 31/16 Amides, e.g. hydroxamic acids
• CPC Class Codes: A61K 31/17 having the group >N—C(O)—N< or >N—C(S)—N<, e.g. urea, thiourea, carmustine isoureas, isothioureas A61K31/155; sulfonylureas A61K31/64
• CPC Class Codes: A61K 31/18 Sulfonamides compounds containing a para-N-benzene-sulfonyl-N- group A61K31/63
• CPC Class Codes: A61K 31/4166 having oxo groups directly attached to the heterocyclic ring, e.g. phenytoin
• CPC Class Codes: A61K 31/505 Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
• CPC Class Codes: A61K 31/522 having oxo groups directly attached to the heterocyclic ring, e.g. hypoxanthine, guanine, acyclovir
• CPC Class Codes: A61K 31/54 having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame
• CPC Class Codes: A61K 31/541 Non-condensed thiazines containing further heterocyclic rings
• CPC Class Codes: A61K 31/549 having two or more nitrogen atoms in the same ring, e.g. hydrochlorothiazide
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 1/18 for pancreatic disorders, e.g. pancreatic enzymes
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 13/08 of the prostate
• CPC Class Codes: A61P 13/10 of the bladder
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 25/00 : Drugs for disorders of the nervous system
• CPC Class Codes: A61P 35/00 : Antineoplastic agents
• CPC Class Codes: A61P 35/02 : specific for leukemia
• CPC Class Codes: A61P 35/04 : specific for metastasis
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

The invention provides a method of inhibiting tumor growth in a mammal, by administering to the mammal composition containing taurolidine, taurultam, or a biologically active derivative thereof. The composition is administered to directly contact a tumor cell at a dose sufficient to induce cell death by apoptosis.

Claims

1. A method of killing a tumor cell in a mammal, comprising administering to said mammal a composition comprising taurolidine, taurultam or a biologically active derivative thereof, wherein said composition is administered to directly contact the surface of said tumor cell at a dose sufficient to induce tumor cell death by apoptosis, wherein said tumor cell is a urinary bladder carcinoma.

2. The method of claim 1, wherein said bladder is inflated with a solution comprising said composition.

3. A method of killing a tumor cell in a mammal, comprising administering to said mammal a composition comprising taurolidine, taurultam or a biologically active derivative thereof, wherein said composition is administered to directly contact the surface of said tumor cell at a dose sufficient to induce tumor cell death by apoptosis, wherein said tumor cell is a malignant skin cell.

4. The method of claim 3, wherein said malignant skin cell is a basal cell carcinoma or a squamous cell carcinoma.

5. The method of claim 3, wherein said malignant skin cell is a melanoma, sarcoma, or lymphoma.

6. The method of claim 3, wherein said composition is formulated in an ointment, said ointment being administered directly to said malignant skin cell.

7. A method of killing a tumor cell in a mammal, comprising administering to said mammal a composition comprising taurolidine, taurultam or a biologically active derivative thereof, wherein said composition is administered to directly contact the surface of said tumor cell at a dose sufficient to induce tumor cell death by apoptosis, wherein said tumor cell is a liver cancer.

8. A method of killing a tumor cell in a mammal, comprising administering to said mammal a composition comprising taurolidine, taurultam or a biologically active derivative thereof, wherein said composition is administered to directly contact the surface of said tumor cell at a dose sufficient to induce tumor cell death by apoptosis, wherein said composition is administered by infusion into a blood vessel of the liver.

9. A method of killing a tumor cell in a mammal, comprising administering to said mammal a composition comprising taurolidine, taurultam or a biologically active derivative thereof, wherein said composition is administered to directly contact the surface of said tumor cell at a dose sufficient to induce tumor cell death by apoptosis, wherein said composition is administered by infusion into the hepatic artery.

10. A method of killing a tumor cell in a mammal, comprising administering to said mammal a composition comprising taurolidine, taurultam or a biologically active derivative thereof, wherein said composition is administered to directly contact the surface of said tumor cell at a dose sufficient to induce tumor cell death by apoptosis, wherein said composition is administered by infusion into the portal vein.

11. A method of purging a population of bone marrow cells of tumor cells ex vivo, comprising contacting said population with a composition comprising taurolidine, taurultam, or a biologically active derivative thereof.

12. The method of claim 11, wherein said composition comprises taurolidine.

13. The method of claim 11, wherein said composition comprises taurultam.

14. The method of claim 11, wherein said population is contacted with an amount of said composition sufficient to induce tumor cell death by apoptosis.

15. The method of claim 11, wherein said population is contacted with an amount of composition which preferentially induces apoptosis in said tumor cells compared to necrosis of said tumor cells.

16. A method of purging a population of peripheral blood mononuclear cells of tumor cells, comprising contacting said population with a composition comprising taurolidine, taurultam, or a biologically active derivative thereof.

17. The method of claim 16, wherein said composition comprises taurolidine.

18. The method of claim 16, wherein said composition comprises taurultam.

19. The method of claim 16, wherein the number of tumor cells in said population is reduced by at lest five log units.

20. A therapeutic film-forming composition comprising taurolidine, taurultam, or a biologically active derivative thereof.

21. The composition of claim 20, wherein said compound is in the form of an ointment, paste, spray, patch, cream, gel, resorbable sponge, or foam.

22. The composition of claim 20, wherein said compound is in the form of an adhesive patch.