Vitamin K2 compositions for the treatment of drug induced neuropathy

Abstract

The present invention provides the use of vitamin K2 compositions for the treatment of drug-induced neuropathy. More particularly it is related to the use of vitamin K2-7 compositions for the treatment of drug-induced peripheral neuropathy caused by the drugs used for the treatment of multiple myeloma.

Claims

1. A method of treating or ameliorating a symptom of cancer drug-induced peripheral neuropathy in a patient suffering from multiple myeloma, the method comprising administering a composition consisting essentially of vitamin K2-7 to the patient, wherein the peripheral neuropathy is caused by the cancer drug used in the treatment of multiple myeloma and the vitamin K2-7 is effective in treating or ameliorating at least one symptom of cancer drug-induced peripheral neuropathy.

2. The method of claim 1, wherein the cancer drug used in the treatment of multiple myeloma is selected from the group consisting of a proteasome inhibitor, an immune suppressant, a steroid, a corticosteroid, an immune modulator, a bisphosphonate, a monoclonal antibody, a vinca alkaloid, and combinations thereof.

3. The method of claim 2, wherein the proteasome inhibitor is Bortezomib.

4. The method of claim 2, wherein the immune suppressant is Cyclophosphamide.

5. The method of claim 2, wherein the steroid is Prednisolone.

6. The method of claim 2, wherein the corticosteroid is Dexamethasone.

7. The method of claim 2, wherein the immune modulator is lenalidomide.

8. The method of claim 2, wherein the bisphosphonate is zoledronic acid.

9. The method of claim 2, wherein the monoclonal antibody is Rituximab.

10. The method of claim 2, wherein the vinca alkaloid is vincristine.

11. The method of claim 1, wherein the dose of vitamin K2-7 is in the range of 50 μg/day to 1100 μg/day.

12. The method of claim 1, wherein the duration for lowering the symptoms of the drug induced peripheral neuropathy from severe to mild is in the range 2-5 months.

13. A method of preventing the symptoms of cancer drug-induced peripheral neuropathy in a patient suffering from multiple myeloma, the method comprising administering vitamin K2-7 to the patient, wherein the peripheral neuropathy is caused by the cancer drug used in the treatment of multiple myeloma and the vitamin K2-7 is effective in treating or ameliorating at least one symptom of cancer drug-induced peripheral neuropathy.

Description

BRIEF DESCRIPTION OF THE DRAWING

(1) The FIGURE is a visual analog scale (VAS) with gradations judged by a physician based on the following criteria. By using Visual Analog Scale, i.e. 0-10 point scale: 0=Absent; 1-3=Mild; 4-6=Moderate; 7-10=Severe.

DETAILED DESCRIPTION OF THE INVENTION

(2) Vitamin K2-7 is now a well-established nutraceutical in the industry and its applications are well established. While developing newer applications of vitamin K2-7, it has now been surprisingly found that vitamin K2-7 ameliorates the symptoms of peripheral neuropathy caused by drugs used in the treatment of multiple myeloma.

(3) The present invention relates to the therapeutic uses of vitamin K. It refers to compositions comprising vitamin K2-7 for the treatment of drug-induced neuropathy. More specifically, it refers to the compositions comprising vitamin K2-7 for the treatment of drug-induced peripheral neuropathy caused during the treatment of multiple myeloma.

(4) Vitamin K2-7 compositions of the invention is in the form of capsule, tablets, syrups, and sachets.

(5) In another embodiment of the invention, vitamin K2-7 compositions are used for treatment of peripheral neuropathy caused by drugs for the treatment of autoimmune diseases, such as etanercept, infliximab, leflunomide, azathioprine, cyclophosphamide, cyclosporine, mycophenolate, and methotrexate.

(6) In one embodiment, the invention provides a vitamin K2-7 composition and use for treatment of peripheral neuropathy caused by anti-infectives, such as chloroquine, isoniazid, metronidazole, nitrofurantoin, and thalidomide.

(7) In addition, the vitamin K2-7 composition is used for treatment of peripheral neuropathy caused by anti-cancer drugs, such as cisplatin, vincristine, and paclitaxel.

(8) In another aspect of the invention, the vitamin K2-7 composition is used for treatment of peripheral neuropathy caused by anti-HIV drugs, such as didanosine, stavudine, and zalcitabine.

(9) The invention also provides vitamin K2-7 composition for use in treatment of peripheral neuropathy caused by administration of drugs during the treatment of alcohol abuse, such as disulfiram.

(10) In another aspect, the invention provides vitamin K2-7 compositions for use in the treatment of peripheral neuropathy caused by cardiovascular drugs, such as statins, especially simvastatin, pravastatin, fluvastatin, and amiodarone.

(11) The vitamin K2-7 compositions are also used for treatment of peripheral neuropathy caused by drugs for the treatment of multiple myeloma, e.g. bortezomib and thalidomide. In another aspect, the vitamin K2-7 compositions are also used for treatment of peripheral neuropathy caused by drugs for the treatment of multiple myeloma, wherein the said drugs are selected from the group consisting of proteasome inhibitors (e.g. bortezomib), immune suppressants (e.g. cyclophosphamide), steroids (e.g. prednisolone), corticosteroids (e.g. dexamethasone), immune modulators (e.g. lenalidomide), bisphosphonates (e.g. zolendroic acid), monoclonal antibodies (e.g. rituximab), and vinca alkaloids (e.g. vincristine), or a combination thereof.

(12) In another aspect of the invention, the vitamin K2-7 compositions are used for treatment of peripheral neuropathy caused by drugs lenalidomide and dexamethasone.

(13) The invention also encompasses vitamin K2-7 compositions composition for use in the treatment of peripheral neuropathy caused by drugs lenalidomide and zolendroic acid or lenalidomide, dexamethasone, and zolcndroic acid.

(14) Furthermore, the invention provides vitamin K2-7 compositions for use in the treatment of peripheral neuropathy caused by drugs bortezomib, cyclophosphamide, and dexamethasone.

(15) In an aspect of the invention, the composition comprises preferable 100 μg-700 μg of vitamin K2-7/day or more preferably 50 μg-1100 μg vitamin K2-7/day.

(16) In an aspect of the invention, the composition of the invention is administered once or twice daily. It is envisaged that the vitamin K2-7 administered is released in the intestine.

(17) In an aspect of the invention, the vitamin K2-7 composition of the invention is administered to a patient suffering from drug-induced peripheral neuropathy not cured by administration of vitamin B12.

(18) In one aspect of the invention, the composition of the invention administered to a patient suffering from drug-induced peripheral neuropathy minimises or lowers the symptoms of drug-induced peripheral neuropathy.

(19) In another aspect of the invention, the composition of the invention administered to a patient suffering from drug-induced peripheral neuropathy eliminates the symptoms of drug-induced peripheral neuropathy.

(20) In yet another aspect of the invention, the composition of the invention administered to a patient simultaneously with the drugs that are reported to cause peripheral neuropathy minimises the symptoms of drug-induced peripheral neuropathy.

(21) In an aspect of the invention, the composition of the invention administered to a patient simultaneously with the drugs that are reported to cause peripheral neuropathy prevents the occurrence of the symptoms of drug-induced peripheral neuropathy.

(22) In an aspect of the invention, the composition of the invention administered to a patient simultaneously with the drugs that are reported to cause peripheral neuropathy, enables continued administration of the drugs for the treatment of multiple myeloma by minimizing the symptoms of drug-induced neuropathy.

(23) In an aspect of the invention, the composition of the invention administered to a patient prior to the administration of the drugs that are reported to cause peripheral neuropathy prevents the occurrence of the symptoms of drug-induced peripheral neuropathy.

(24) In an aspect of the invention, the vitamin K2-7 composition of the invention administered to a patient prior to the administration of the drugs that are reported to cause peripheral neuropathy minimises the symptoms of drug-induced peripheral neuropathy.

(25) In an aspect of the invention, the vitamin K2-7 composition of the invention is administered to patient 2-24 weeks prior to the administration of the drugs that are reported to cause the symptoms of drug-induced peripheral neuropathy.

(26) The composition comprising vitamin K2-7 of the invention is used for the treatment of peripheral neuropathy, wherein upon administration of vitamin K2-7, the patient is relieved of the symptoms of peripheral neuropathy during the next cycle of administration of the drugs for the treatment of multiple myeloma. Hence, vitamin K2-7 is used as a preventive nutraceutical to prevent the occurrence of symptoms of drug-induced peripheral neuropathy.

(27) The beneficial effects on administration of vitamin K2-7 to patients suffering from chemotherapy-induced peripheral neuropathy during the treatment of multiple myeloma are now described below with examples which are illustrative and should not be in anyway considered as limiting the scope of the invention.

Example 1

(28) An open labelled study was conducted to evaluate the effect of vitamin K2-7 on drug-induced peripheral neuropathy. Patients who were diagnosed with multiple myeloma and are on chemotherapy treatment for the same, were assessed for the occurrence of symptoms of peripheral neuropathy and then selected. Patients were given 2 capsules of 100 mcg or 350 mcg of vitamin K2-7 along with the ongoing chemotherapy. The evaluation of symptoms of peripheral neuropathy (such as tingling, numbness, burning sensation, muscle cramps etc.) were assessed by VAS score (Schematic 1) from 0 to 10 (nil to unbearable). The scale has been used in various studies to measure the intensity and severity of various symptoms of neuropathy [8, 9].

(29) It was observed that before the beginning of vitamin K2-7 therapy, the VAS score in all the patients was between the range of “8” and “9” for the symptoms of tingling, numbness and burning sensation. As the patients continued with the therapy, it was observed that the VAS score for all the symptoms decreased to between the range of “1” and “2”. This decrease has happened over a period of 2 to 5 months, depending upon the individual cases treated. Further, no adverse events were noted during the vitamin K2-7 therapy. Hence, it can be concluded that vitamin K2-7 helps in relieving the symptoms of drug-induced peripheral neuropathy significantly and helps patient for better compliance to the chemotherapeutic agents. The examples given in Table 1, summarises the data for 11 patients who were on vitamin K2-7 therapy for drug-induced peripheral neuropathy due to treatment for multiple myeloma. In Table 1, treatment administered refer to the cyclical chemotherapy provided to the patients of multiple myeloma (MM). These cycles are normally of 3 weeks or 21 days period, based on the attending physician's assessment of the patient's condition and tolerance.

(30) However, vitamin K2-7 was administered daily as two 100 mg capsules. If patient did not respond to the 200 mg dose of vitamin K2-7 for a period of 2 cycles, then they were administered 350 μg/day of vitamin K2-7.

(31) Thus, out of 11 patients, 1 patient remained on 100 μg of vitamin K2-7, two times a day daily, with significant improvement in peripheral neuropathy.

(32) Treatment with vitamin K2-7 of subjects continued even after their having reached VAS score of “2”. Such continues treatment stabilised the VAS Score. Further, it was noticed that continuation of vitamin K2-7 during the subsequent cycles prevented the flair up of the symptoms of drug-induced peripheral neuropathy. It was also observed that in patients administered with vitamin K2-7, the compliance rate of the for chemotherapy were improved significantly.

(33) The gradation was judged by Physician based on following criteria. By using Visual Analog Scale, i.e. 0-10 point scale: 0=Absent; 1-3=Mild; 4-6=Moderate; 7-10=Severe.

(34) TABLE-US-00001 TABLE 1 Summary of 11 patients receiving Vitamin K2-7 therapy for Drug induced Peripheral Neuropathy due to treatment for Multiple myeloma Start of Date and Dosage of VAS Score Patient Treatment for Treatment Administration of before starting VAS ID MM Administered* Vitamin K2-7 Vitamin K2-7 Date Score 1 June 2014 1, 2, 3 16 Jun. 15 (350 μg) 8 10 Dec. 15 2 2 2014 4, 3 25 Jun. 15 (350 μg) 8 05 Nov. 15 2 3 2015 4, 3, 5 19 Aug. 15 (100 μg) 8 14 Mar. 16 2 4 2015 1, 2, 3 09 Jun. 16 (350 μg) 8 22 Dec. 16 1 5 2016 1, 2, 3 23 Feb. 17 (350 μg) 9 12 Aug. 17 2 6 November 2014 6, 2, 7, 8, 9 22 May 17 (350 μg) 9 04 Oct. 17 2 7 2010 4, 3 30 Jun. 17 (350 μg) 8 27 Dec. 17 2 8 March 2017 1, 2, 3 03 Nov. 17 (350 μg) 7 03 Apr. 18 2 9 2016 1, 2, 3 20 Jul. 16 (350 μg) 9 11 Jan. 17 2 10 2016 4, 3 10 Jun. 17 (350 μg) 8 10 Jan. 18 3 11 2016 3 25 Mar. 17 (350 μg) 9 29 Sep. 17 2 *1-Bortezomib, 2-Cyclophosphamide, 3-Dexamethasone, 4-Lenalidomide, 5-Zolendronic Acid, 6-Rituximab, 7- Doxorubicin, 8-Vincristine, 9-Prednisolone

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