2-HYDROXYOCTADECENE-9-CIS-OAT FOR USE IN THE TREATMENT OF ONCOLOGICAL PATHOLOGIES AND NEUROPATHIC PAIN

Claims

1. The compound 2-hydroxyoctadecene-9-cis-oate or a pharmaceutically acceptable salt or ester thereof for use in the treatment of an oncological pathology selected from the group consisting of glioblastoma, astrocytoma, pilocytic astrocytoma, diffuse astrocytoma, anaplastic astrocytoma, oligoastrocytoma, oligodendroglioma, ependymoma, xanthoastrocytoma, medulloblastoma, low-grade glioma, grade 3 glioma, brainstem glioma, ependymal tumor, subependymoma, gliomatosis cerebri, embryonal tumor, atypical teratoid-rhabdoid tumor, tumor of the cranial and spinal nerves, mixed neuronal-glial tumor, pituitary tumor, germ cell tumor, tumor of the meninges, meningiomas, hemangiopericytomas, hemangioblastomas, choroid plexus tumors, choroid plexus papillomas, pineocytomas, pineoblastomas, mesotheliomas, pleural mesotheliomas, bile duct adenocarcinomas,exocrine pancreatic cancer, neuroendocrine pancreatic cancer, metastatic lung adenocarcinoma, small cell lung cancer, colon adenocarcinoma, rectal cancer, rectosigmoid junction cancer, rectal adenocarcinoma, metastatic rectal adenocarcinoma, metastatic sigmoid colon adenocarcinoma, colorectal adenocarcinoma, metastatic colorectal adenocarcinoma, urachus fistula cancer, urachus adenocarcinoma, endometrial adenocarcinoma, neuroendocrine pancreatic cancer, pancreatic adenocarcinoma, uterine chondrosarcoma, adenocarcinoma of the cecum, esophageal cancer and metastatic small cell esophageal cancer, wherein the said compound is administered at a dose of 500 mg / day to 16000 mg / day, 2. A compound, salt or ester for use according to claim 1, characterized in that said oncological pathology is selected from the group consisting of oligoastrocytoma, glioblastoma, oligodendroglioma, ependymoma, xanthoastrocytoma, medulloblastoma, pilocytic astrocytoma, brainstem glioma, ependymal tumor, subependymoma, gliomatosis cerebri, embryonal tumor, atypical teratoid-rhabdoid tumor, tumor of the cranial and spinal nerves, mixed neuronal-glial tumor, pituitary tumor, germ cell tumor, tumor of the meninges, meningioma, hemangiopericytoma, hemangioblastoma, tumor of the choroid plexus, papilloma of the choroid plexus, pineocytoma, pineoblastoma, mesothelioma, pleural mesothelioma, bile duct adenocarcinoma, exocrine pancreatic cancer, neuroendocrine pancreatic cancer, metastatic lung adenocarcinoma, small cell lung cancer, colorectal cancer,Rectosigmoid junction cancer, metastatic rectal adenocarcinoma, metastatic sigmoid adenocarcinoma, colorectal metastatic adenocarcinoma, urachus fistula cancer, urachus adenocarcinoma, endometrial cancer, pancreatic neuroendocrine cancer, uterine chondrosarcoma, cecal adenocarcinoma, bladder adenocarcinoma, esophageal cancer, and metastatic small cell esophageal cancer.

3. A compound, salt or ester for use according to claim 1 or 2, wherein said glioblastoma is grade IV glioblastoma multiforme with native isocitrate dehydrogenase (IDH) enzyme.

4. A compound, salt, or ester for use according to claim 3 for use in the treatment of grade IV glioblastoma multiforme with native IDH in a subject who exhibits methylation of the methylguanine methyltransferase (MGMT) gene promoter.

5. A compound, salt or ester for use according to any one of claims 1 to 4, wherein said salt is a sodium salt.

6. A compound, salt or ester for use according to any one of claims 1 to 5, wherein said ester is a methyl ester or an ethyl ester.

7. A compound, salt or ester for use according to any one of claims 1 to 6, characterized in that said compound, salt or ester is administered orally.

8. A compound, salt, or ester for use according to any one of claims 1 to 7, which is administered at a dose selected from the group consisting of 500 mg / day, 1000 mg / day, 1050 mg / day, 2000 mg / day, 2100 mg / day, 3150 mg / day, 4000 mg / day, 4200 mg / day, 6000 mg / day, 6300 mg / day, 8000 mg / day, 10000 mg / day, 12000 mg / day, 12600 mg / day, 14000 mg / day, and 16000 mg / day.

9. A compound, salt, or ester for use according to any one of claims 1-8, which is administered at a dose of 2100 mg / day.

10. A compound, salt, or ester for use according to any one of claims 1-8, which is administered at a dose of 12,000 mg / day.

11. A compound, salt or ester for use according to any one of claims 1 to 10, characterized in that said compound, salt or ester is used as a first-line therapy.

12. A compound, salt, or ester for use according to claim 11, wherein the first-line therapy consists of 4-week cycles, wherein each cycle comprises daily administration of said compound, salt, or ester for the first three weeks of each cycle, with no treatment being administered during the fourth week.

13. A compound, salt or ester for use according to any one of claims 1 to 12, wherein said compound, salt or ester is used as a preoperative or postoperative treatment to reduce the size of a tumor.

14. A compound, salt or ester for use according to any one of claims 1 to 12, wherein the subject receiving treatment has previously been treated with at least one or up to five different lines of chemotherapy.

15. A compound, salt or ester for use according to any one of claims 1-10, 13 or 14, characterized in that said compound, salt or ester is used as a maintenance treatment.

16. A compound, salt, or ester for use according to claim 15, wherein the maintenance treatment consists of 4-week cycles, wherein each cycle comprises daily administration of said compound, salt, or ester during the first three weeks of each cycle, and no treatment is administered during the fourth week.

17. A compound, salt or ester for use according to any one of paragraphs 1-16, characterized in that the treatment comprises: a chemoradiation therapy phase lasting 6 to 7 weeks, including daily administration of radiation therapy, 5 days a week; administration of a second chemotherapeutic agent at a daily dose of 75 mg / m 2 , starting on the first day of radiation therapy; and administration of the proposed compound, salt, or ester at a dose of 12,000 mg / day for 4 weeks, starting at week 3 from the start of radiation therapy; 4-week break in treatment; A 4-week maintenance period consisting of 6 cycles, with each cycle including the administration of a second chemotherapeutic agent at a daily dose of 150 to 200 mg / m 2 during the first five days of each cycle; administration of the proposed compound, salt, or ester at a dose of 12,000 mg / day during the first three weeks of each cycle, with no treatment during the fourth week; and a monotherapy phase consisting of 4-week cycles, wherein each cycle includes the administration of the proposed compound, salt or ester at a dose of 12,000 mg / day during the first three weeks of each cycle, with no treatment during the fourth week, and these cycles continuing indefinitely as maintenance therapy.

18. A compound, salt or ester for use according to any one of claims 1 to 17 for simultaneous, separate or sequential use in combination with a second chemotherapeutic agent selected from the group consisting of temozolomide, thiamine, gemcitabine, fluorouracil, oxyplatin, irinotecan, etoposide, imatinib, folfirinox, erlotinib and cisplatin.

19. A compound, salt or ester for use according to claim 18 for simultaneous, separate or sequential use in combination with temozolomide for the treatment of glioblastoma.

20. A compound, salt, or ester for use according to claim 19, wherein the glioblastoma is grade IV glioblastoma multiforme with native IDH.

21. The compound 2-hydroxyoctadecene-9-cis-oate or a pharmaceutically acceptable salt or ester thereof for use in the treatment of neuropathic pain, which is administered at a dose of 500 mg / day to 16,000 mg / day.

22. A compound, salt or ester for use according to claim 21, wherein said neuropathic pain is caused by damage to neurons or damage to nerves of the central and / or peripheral nervous system.

23. A compound, salt, or ester for use according to claim 22, wherein said neuronal injury is spinal cord injury.

24. A compound, salt or ester for use according to claim 21, wherein said neuropathic pain is caused by a cause selected from the group consisting of a chemotherapeutic agent, an antitumor agent and an anticancer agent.

25. A compound, salt or ester for use according to claim 24, wherein said antitumor agent is an alkaloid.

26. A compound, salt or ester for use according to claim 25, wherein the alkaloid is vincristine.

27. A compound, salt or ester for use according to claim 21, wherein said neuropathic pain is caused by a cause selected from the group consisting of peripheral diabetic neuropathy, postherpetic neuralgia, fibromyalgia and hepatitis.

28. A compound, salt, or ester for use according to any one of claims 21-27, which is administered at a dose selected from the group consisting of 500 mg / day, 1000 mg / day, 1050 mg / day, 2000 mg / day, 2100 mg / day, 3150 mg / day, 4000 mg / day, 4200 mg / day, 6000 mg / day, 6300 mg / day, 8000 mg / day, 10000 mg / day, 12000 mg / day, 12600 mg / day, 14000 mg / day, and 16000 mg / day.

29. A compound, salt, or ester for use according to any one of paragraphs 21-28, which is administered at a dose of 2100 mg / day.

30. A compound, salt, or ester for use according to any one of paragraphs 21-28, which is administered at a dose of 4200 mg / day.

31. A compound, salt or ester for use according to any one of claims 21 to 30 for simultaneous, separate or sequential use in combination with at least one other active ingredient selected from the group consisting of pregabalin, an opioid analgesic, a steroid analgesic, a non-steroidal analgesic, a cannabinoid analgesic, an anticonvulsant, an anxiolytic, an anesthetic and an antidepressant.

32. A compound, salt or ester for use according to any one of claims 21-31 for simultaneous, separate or sequential use in combination with at least one other active ingredient selected from the group consisting of lamotrigine, omeprazole, phenoxypentanoic acid, metformin, ibuprofen, dulcolax, alprazolam, diazepam, baclofen, macrogol, duloxetine, levofloxacin, gabapentin, ceftriaxone, enoxaparin, pantoprazole, paracetamol, ipratropium bromide, acetylcysteine, metoclopramide, metamizole, teicoplanin, dexketoprofen, oxybutynin, meropenem, beclomethasone dipropionate, formoterol fumarate, atorvastatin, calcifediol, paroxetine, cyanocobalamin, clonazepam, amlodipine, trazodone, flurazepam, thiazides, losartan, metamizole, sucralfate, lactitol, pancreatin, dimethicone, bethanechol, amitriptilian, lorazepam, vitamin D, lormetazepam, solifenacin, simvastatin, cinitapride, quetiapine, betmig, valproate, lacosamide, lidocaine,Metamizole, finasteride, acetylsalicylic acid, enalapril, metformin, liraglutide, trospium, tramadol, celcoxib, citalopram, sildenafil, tamsulosin, loratadine, tizanidine, vortioxetine, zolpidem, bromazepam, dexamethasone, dexketoprofen, losartan, eslicarbazepine, pentoxifylline, mirabegron, fluoxetine, clorazepate, mirtazapine, rosuvastatin, prednisone, beclomethasone, methylprednisone, acyclovir, lidocaine, nystatin, delorazepam, alendronic acid, carbamazepine, cortisone, hydrocortisone, cannabidiol and tetrahydrocannabinol.

33. A pharmaceutical composition comprising a 2-hydroxyoctadecene-9-cis-oate compound or a pharmaceutically acceptable salt or ester thereof together with at least one pharmaceutically acceptable excipient or carrier for use in the treatment of an oncological pathology selected from the group consisting of glioblastoma multiforme, astrocytoma, pilocytic astrocytoma, diffuse astrocytoma, anaplastic astrocytoma, oligoastrocytoma, oligodendroglioma, ependymoma, xanthoastrocytoma, medulloblastoma, low-grade glioma, grade 3 glioma, brainstem glioma, ependymal tumor, subependymoma, gliomatosis cerebri, embryonal tumor, atypical teratoid-rhabdoid tumor, tumor of the cranial and spinal nerves, mixed neuronal-glial tumor, pituitary tumor, germ cell tumor, tumor of the meninges, meningioma, hemangiopericytoma, hemangioblastoma,Choroid plexus tumors, choroid plexus papillomas, pineocytomas, pineoblastomas, mesothelioma, pleural mesothelioma, bile duct adenocarcinoma, exocrine pancreatic cancer, pancreatic neuroendocrine cancer, metastatic lung adenocarcinoma, small cell lung cancer, colon adenocarcinoma, rectal cancer, rectosigmoid junction cancer, rectal adenocarcinoma, metastatic rectal adenocarcinoma, metastatic sigmoid colon adenocarcinoma, colorectal adenocarcinoma, metastatic colorectal adenocarcinoma, urachus fistula cancer, urachus adenocarcinoma, endometrial adenocarcinoma, pancreatic neuroendocrine cancer, pancreatic adenocarcinoma glands, chondrosarcoma of the uterus, adenocarcinoma of the cecum, adenocarcinoma of the bladder, esophageal cancer and metastatic small cell esophageal cancer, wherein the said compound,the salt or ester is administered in a dose of 500 mg / day to 16,000 mg / day, 34. The pharmaceutical composition according to claim 33, characterized in that the oncological pathology is selected from the group consisting of oligoastrocytoma, glioblastoma, oligodendroglioma, ependymoma, xanthoastrocytoma, medulloblastoma, pilocytic astrocytoma, brainstem glioma, ependymal tumor, subependymoma, gliomatosis cerebri, embryonal tumor, atypical teratoid-rhabdoid tumor, tumor of the cranial and spinal nerves, mixed neuronal-glial tumor, pituitary tumor, germ cell tumor, tumor of the meninges, meningioma, hemangiopericytoma, hemangioblastoma, tumor of the choroid plexus, papilloma of the choroid plexus, pineocytoma, pineoblastoma, mesothelioma, pleural mesothelioma, bile duct adenocarcinoma, exocrine pancreatic cancer, neuroendocrine pancreatic cancer, metastatic lung adenocarcinoma, small cell lung cancer, rectal cancer, rectosigmoid junction cancer,Metastatic rectal adenocarcinoma, metastatic sigmoid colon adenocarcinoma, metastatic colorectal adecal carcinoma, urachus fistula cancer, urachus adenocarcinoma, endometrial cancer, pancreatic neuroendocrine cancer, uterine chondrosarcoma, cecal adenocarcinoma, bladder adenocarcinoma, esophageal cancer, and metastatic small cell esophageal cancer.

35. A pharmaceutical composition according to claim 33 or 34, characterized in that the glioblastoma is a grade IV glioblastoma multiforme with native isocitrate dehydrogenase (IDH) enzyme.

36. The pharmaceutical composition of claim 35 for use in the treatment of grade IV glioblastoma multiforme with native IDH in a subject exhibiting methylation of the methylguanine methyltransferase (Mgmt) gene promoter.

37. A pharmaceutical composition according to any one of paragraphs 33-36, characterized in that said salt is a sodium salt.

38. A pharmaceutical composition according to any one of paragraphs 33-37, characterized in that said ester is a methyl ester or an ethyl ester.

39. The pharmaceutical composition according to any one of paragraphs. 33-38, characterized in that said compound, salt or ester is administered in a dose selected from the group consisting of 500 mg / day, 1000 mg / day, 1050 mg / day, 2000 mg / day, 2100 mg / day, 3150 mg / day, 4000 mg / day, 4200 mg / day, 6000 mg / day, 6300 mg / day, 8000 mg / day, 10000 mg / day, 12000 mg / day, 12600 mg / day, 14000 mg / day and 16000 mg / day.

40. A pharmaceutical composition according to any one of paragraphs 33-39, characterized in that said compound, salt or ester is administered at a dose of 2100 mg / day.

41. A pharmaceutical composition according to any one of paragraphs 33-39, characterized in that said compound, salt or ester is administered at a dose of 12,000 mg / day.

42. The pharmaceutical composition according to any one of claims 33-41, further comprising a second chemotherapeutic agent selected from the group consisting of temozolomide, thiamine, gemcitabine, fluorouracil, oxyplatin, irinotecan, etoposide, imatinib, folfirinox, erlotinib and cisplatin.

43. The pharmaceutical composition according to any one of claims 33-42, further comprising temozolomide for use in the treatment of glioblastoma.

44. The pharmaceutical composition according to claim 43, characterized in that the glioblastoma is a grade IV glioblastoma multiforme with native IDH.

45. A pharmaceutical composition comprising the compound 2-hydroxyoctadecene-9-cisoate or a pharmaceutically acceptable salt or ester thereof together with at least one pharmaceutically acceptable excipient or carrier for use in the treatment of neuropathic pain, wherein said compound, salt or ester is administered at a dose of from 500 mg / day to 16,000 mg / day.

46. ​​The pharmaceutical composition according to claim 45, characterized in that neuropathic pain is caused by damage to neurons or damage to nerves of the central and / or peripheral nervous system.

47. The pharmaceutical composition according to claim 46, characterized in that said neuronal damage is spinal cord damage.

48. The pharmaceutical composition according to claim 45, characterized in that said neuropathic pain is caused by a cause selected from the group consisting of a chemotherapeutic agent, an antitumor agent, and an anticancer agent.

49. The pharmaceutical composition according to claim 48, characterized in that said antitumor agent is an alkaloid.

50. The pharmaceutical composition according to claim 49, characterized in that the alkaloid is vincristine.

51. The pharmaceutical composition according to claim 45, characterized in that said neuropathic pain is caused by a cause selected from the group consisting of diabetic peripheral neuropathy, postherpetic neuralgia, fibromyalgia and hepatitis.

52. The pharmaceutical composition according to any one of paragraphs. 45-51, characterized in that said compound, salt or ester is administered in a dose selected from the group consisting of 500 mg / day, 1000 mg / day, 1050 mg / day, 2000 mg / day, 2100 mg / day, 4000 mg / day, 4200 mg / day, 6000 mg / day, 8000 mg / day, 10000 mg / day, 12000 mg / day, 14000 mg / day and 16000 mg / day.

53. A pharmaceutical composition according to any one of paragraphs 45-52, characterized in that said compound, salt or ester is administered at a dose of 2100 mg / day.

54. A pharmaceutical composition according to any one of paragraphs 45-52, characterized in that said compound, salt or ester is administered at a dose of 4200 mg / day.

55. The pharmaceutical composition according to any one of claims 45-54, further comprising at least one other active ingredient selected from the group consisting of pregabalin, an opioid analgesic, a steroidal analgesic, a non-steroidal analgesic, a cannabinoid analgesic, an anticonvulsant, an anxiolytic, an anesthetic, and an antidepressant.

56. The pharmaceutical composition of claim 55, further comprising at least one other active ingredient selected from the group consisting of lamotrigine, omeprazole, phenoxypentanoic acid, metformin, ibuprofen, dulcolax, alprazolam, diazepam, baclofen, macrogol, duloxetine, levofloxacin, gabapentin, ceftriaxone, enoxaparin, pantoprazole, paracetamol, ipratropium bromide, acetylcysteine, metoclopramide, metamizole, teicoplanin, dexketoprofen, oxybutynin, meropenem, beclomethasone dipropionate, formoterol fumarate, atorvastatin, calcifediol, paroxetine, cyanocobalamin, clonazepam, amlodipine, trazodone, flurazepam, thiazides, losartan, metamizole, sucralfate, lactitol, pancreatin, dimethicone, bethanechol, amitriptilian, lorazepam, vitamin D, lormetazepam, solifenacin, simvastatin, cinitapride, quetiapine, betmig, valproate, lacosamide, lidocaine, metamizole, finasteride, acetylsalicylic acid, enalapril, metformin, liraglutide,Trospium, tramadol, celcoxib, citalopram, sildenafil, tamsulosin, loratadine, tizanidine, vortioxetine, zolpidem, bromazepam, dexamethasone, dexketoprofen, losartan, eslicarbazepine, pentoxifylline, mirabegron, fluoxetine, clorazepate, mirtazapine, rosuvastatin, prednisone, beclomethasone, methylprednisone, acyclovir, lidocaine, nystatin, delorazepam, alendronic acid, carbamazepine, cortisone, hydrocortisone, cannabidiol, and tetrahydrocannabinol.