Substituted imidazolium compounds for treating disease
View Patent ↗The present disclosure relates to therapeutic compositions comprising substituted imidazoliums having multiple acidic groups. The compounds may be used to treat diseases or conditions such as those associated with bone, cancer, or pain. Compositions, dosage forms, methods of treating diseases or conditions, methods of preparation, and other related embodiments related to the substituted imidazoliums are also described herein.
1. A pharmaceutical dosage form comprising a compound represented by a formula:
or a salt thereof;
wherein the compound is at least 1% of the total weight of active agent in the pharmaceutical dosage form;
wherein each A is independently an acidic functional group.
2. The pharmaceutical dosage form of claim 1 , wherein each A is CO 2 H.
3. The pharmaceutical dosage form of claim 1 , wherein each A is SO 2 H.
4. A method of treating a disease or condition associated with bone, cancer, or pain, comprising administering a dosage form of claim 1 to a mammal in need thereof;
wherein the disease or condition is acute pain, central pain, radio-therapy or chemo-therapy associated neuropathy, ankylosing spondylitis, arthritis, axial spondyloarthritis, a blood cancer, bone fracture, bone metastases from a solid tumor, bone metastasis, breast cancer, cancer, central multiple sclerosis pain, Charcot's foot, chronic pain, complex regional pain syndrome, diabetic peripheral neuropathy, erosive osteoarthritis, excessive bone resorption, fibrous dysplasia, giant cell tumor of bone, HIV-associated neuropathy, hypercalcemia of malignancy, inflammatory pain, juvenile rheumatoid arthritis, leukemia, low back pain, lumbar nerve root compression, lumbosacral pain, lung cancer, metastatic bone cancer, a monoradiculopathy, multiple myeloma, musculoskeletal pain, a neuropathic arthropathy, neuropathic pain, non-articular rheumatism, osteoarthritis, osteogenesis imperfecta, osteoporosis, Paget's disease of bone, a peri-articular disorder, phantom limb pain, post-herpetic neuralgia, postoperative pain, post-stroke pain, prostate cancer, rheumatoid arthritis, SAPHO syndrome, a sero-negative or non-rheumatoid arthropathy, a solid tumor or cancer, spinal cord injury, systemic lupus erythematosus, transient osteoporosis, transient osteoporosis of the hip, trigeminal neuralgia, tumor induced hypocalcemia, or vertebral crush fracture, or a combination thereof.
5. The method of claim 4 , wherein the mammal is a human being.
6. The method of claim 4 , wherein the disease or condition is an inflammatory pain, arthritis, osteoporosis, multiple myeloma, or bone metastasis from solid tumors.
7. A pharmaceutical dosage form comprising:
(Compound 2), or a salt thereof, in an amount that is at least 1% of the total weight of all therapeutically active agents in the pharmaceutical dosage form.
8. The pharmaceutical dosage form of claim 7 , wherein zoledronic acid is less than 95% w/w of the total amount of all therapeutically active agents present in the pharmaceutical dosage form.
9. The pharmaceutical dosage form of claim 7 , wherein Compound 2, or a salt thereof, is the sole active agent present in the pharmaceutical dosage form.
10. A method of treating a disease or condition associated with bone, cancer, or pain, comprising administering the pharmaceutical dosage form of claim 7 to a mammal in need thereof;
wherein the disease or condition is acute pain, central pain, radio-therapy or chemo-therapy associated neuropathy, ankylosing spondylitis, arthritis, axial spondyloarthritis, a blood cancer, bone fracture, bone metastases from a solid tumor, bone metastasis, breast cancer, cancer, central multiple sclerosis pain, Charcot's foot, chronic pain, complex regional pain syndrome, diabetic peripheral neuropathy, erosive osteoarthritis, excessive bone resorption, fibrous dysplasia, giant cell tumor of bone, HIV-associated neuropathy, hypercalcemia of malignancy, inflammatory pain, juvenile rheumatoid arthritis, leukemia, low back pain, lumbar nerve root compression, lumbosacral pain, lung cancer, metastatic bone cancer, a monoradiculopathy, multiple myeloma, musculoskeletal pain, a neuropathic arthropathy, neuropathic pain, non-articular rheumatism, osteoarthritis, osteogenesis imperfecta, osteoporosis, Paget's disease of bone, a peri-articular disorder, phantom limb pain, post-herpetic neuralgia, postoperative pain, post-stroke pain, prostate cancer, rheumatoid arthritis, SAPHO syndrome, a sero-negative or non-rheumatoid arthropathy, a solid tumor or cancer, spinal cord injury, systemic lupus erythematosus, transient osteoporosis, transient osteoporosis of the hip, trigeminal neuralgia, tumor induced hypocalcemia, or vertebral crush fracture, or a combination thereof.
11. The method of claim 10 , wherein the mammal is a human being.
12. The method of claim 10 , wherein the disease or condition comprises osteoporosis.
13. The method of claim 10 , wherein the disease or condition comprises inflammatory pain.
14. The method of claim 10 , wherein the disease or condition comprises arthritis.
15. The method of claim 10 , wherein the disease or condition comprises multiple myeloma.
16. The method of claim 10 , wherein the disease or condition comprises Paget's disease.
17. The pharmaceutical dosage form of claim 7 , which is an oral dosage form.
18. The method of claim 10 , wherein the dosage form is administered orally.