Pharmaceutical compositions for headache, migraine, nausea and emesis

• US 7,148,208 B2
• Filed: 03/05/2003
• Issued: 12/12/2006
• Est. Priority Date: 09/05/2000
• Status: Expired due to Term

• Current Assignee: Meditor Pharmaceuticals Ltd.
• Original Assignee: Meditor Pharmaceuticals Ltd.
• Inventors: Barkan, Raphael, Mirimsky, Alexander
• Primary Examiner(s): Marschel, Ardin H.
• Assistant Examiner(s): JAGOE, DONNA A
• Application Number:
  US10/382,217
• Publication Number:
  US 20040006044A1
• Time in Patent Office: 1,378 Days
• Field of Search: 514/54, 514/114, 514/227.5, 514/237.8, 514/252.12, 514/331, 514/365, 514/374, 514/400, 514/408, 514/580
• US Class Current: 514/54
• 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 31/17 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 31/66 Phosphorus compounds
• CPC Class Codes: A61P 1/08 for nausea, cinetosis or vertigo; Antiemetics
• CPC Class Codes: A61P 25/06 Antimigraine agents

Abstract

S-alkylsiothiouronium derivatives such as S-ethylisothiouronium diethylphosphate are used for the treatment of headaches, in particular, migraines, as well as for the prevention or treatment of nausea and vomiting. The compositions of the invention are also effective in preventing or alleviating emesis associated with migraines or other medical conditions such as chemotherapy or radiotherapy, as well as other symptoms of migraines including phonophobia and photophobia.

Claims

1. A method of treating headache or migraine, the method comprising the step of administering to a subject in need of such treatment a therapeutically effective amount of a composition consisting essentially of (a) a compound selected from the group consisting of S-methylisothiouronium methylphosphite;

S-methylisothiouronium dimethylphosphate;

S-ethylisothiouronium metaphosphate;

S-ethylisothiouronium ethylphosphite;

S-ethylisothiouronium diethylphosohate;

S-propylisothiourium propylphosphite;

S-isopropylisothiouronium metaphosphate;

S-isopropylisothiouronium isopropylphosphite;

S-butylisothiouronium dibutylphosphate; and

S-isobutylisothiouronium isobutylphosphite, and (b) a pharmaceutically acceptable carrier or diluent;

wherein the composition is formulated as tablets or capsules.

2. The method of claim 1, wherein each of said tablets or capsules comprises between 10 and 300 mg of the compound.

3. The method of claim 1, wherein each of said tablets or capsules comprises between 20 and 200 mg of the compound.

4. The method of claim 1, wherein each of said tablets or capsules comprises between 30 and 80 mg of the compound.

5. The method of claim 1, wherein said therapeutically effective amount ranges of the compound between 0.1 and 3 mg/kg body weight.

6. The method of claim 1, wherein said therapeutically effective amount ranges of the compound between 0.4 and 1.6 mg/kg body weight.

7. The method of claim 1, wherein said therapeutically effective amount ranges of the compound between 0.5 and 1.2 mg/kg body weight.

8. The method of claim 1, wherein said wherein the compound is S-ethylisothiouronium diethylphosphate.

9. The method of claim 1, wherein said therapeutically effective amount is selected such that less than one hour after administration a substantial relief in migraine symptoms is experienced.

10. The method of claim 1, wherein said step of administering the compound is effected following an onset of a headache or a migraine.

11. The method of claim 1, wherein said step of administering the compound is effected at onset of a headache or a migraine.

12. The method of claim 1, wherein the carrier or diluent comprises a sugar, a starch or cellulose preparation or a physiologically acceptable polymer and optionally includes a disintegrating agent or a salt thereof.

13. A method of alleviating nausea or vomiting, the method comprising the step of administering to a subject suffering from nausea or vomiting a therapeutically effective amount of a composition consisting essentially of (a) a compound selected from the group consisting of S-methylisothiouronium methylphosphite;

S-methylisothiouronium dimethylphosphate;

S-ethylisothiouronium metaphosphate;

S-ethylisothiouronium ethylphosphite;

S-ethylisothiouronium diethylphosphate;

S-propylisothiouronium propylphosphite;

S-isopropylisothiouronium metaphosphate;

S-isopropylisothiouronium isopropylphosphite;

S-butylisothiouronium dibutylphosphate; and

S-isobutylisothiouronium isobutylphosphite, and (b) a pharmaceutically acceptable carrier or diluent;

wherein the composition is formulated as tablets or capsules.

14. The method of claim 13, wherein each of said tablets or capsules comprises between 10 and 300 mg of the compound.

15. The method of claim 13, wherein each of said tablets or capsules comprises between 20 and 200 mg of the compound.

16. The method of claim 13, wherein each of said tablets or capsules comprises between 30 and 80 mg of the compound.

17. The method of claim 13, wherein said therapeutically effective amount ranges of the compound between 0.1 and 3 mg/kg body weight.

18. The method of claim 13, wherein said therapeutically effective amount ranges of the compound between 0.4 and 1.6 mg/kg body weight.

19. The method of claim 13, wherein said therapeutically effective amount ranges of the compound between 0.5 and 1.2 mg/kg body weight.

20. The method of claim 13, wherein the compound is S-ethylisothiouronium diethylphosphate.

21. The method of claim 13, wherein the carrier or diluent comprises a sugar, a starch or cellulose preparation or a physiologically acceptable polymer and optionally includes a disintegrating agent or a salt thereof.

22. A method of alleviating nausea or vomiting resulting from the administration of an anticancer agent or treatment, the method comprising the step of administering to a subject in need thereof a therapeutically effective amount of a composition that comprises (a) a compound having the general formula:

23. The method of claim 22, wherein the anticancer agent or treatment is selected from the group consisting of chemotherapy or radiotherapy.

24. The method of claim 22, wherein the carrier or diluent comprises a sugar, a starch or cellulose preparation or a physiologically acceptable polymer and optionally includes a disintegrating agent or a salt thereof.