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JP-2026076226-A - Compositions and methods for treating Alzheimer's disease and Parkinson's disease

JP2026076226AJP 2026076226 AJP2026076226 AJP 2026076226AJP-2026076226-A

Abstract

[Problem] To provide a pharmaceutical composition combining azelastine and methylcobalamin. [Solution] An orally administered pharmaceutical composition is provided, comprising azelastine or a pharmaceutically acceptable salt of azelastine, methylcobalamin, and one or more pharmaceutically acceptable excipients, wherein the pharmaceutical composition is formulated as a capsule, caplet, tablet, or pill configured for oral administration and absorption in the gastrointestinal tract, and the azelastine or a pharmaceutically acceptable salt of azelastine and methylcobalamin are present together in the pharmaceutical composition in a therapeutically effective daily dose for treating Alzheimer's disease or Parkinson's disease in human patients. [Selection Diagram] None

Inventors

  • ワン，ジャンミン
  • ツイ，ゲピン

Assignees

  • ラ ファーマテック インコーポレイテッド

Dates

Publication Date
20260511
Application Date
20260119

Claims (20)

  1. Azelastine or a pharmaceutically acceptable salt of azelastine, Methylcobalamin, A pharmaceutical composition comprising one or more pharmaceutically acceptable excipients.
  2. The pharmaceutical composition according to claim 1, wherein azelastine or a pharmaceutically acceptable salt of azelastine is present in the pharmaceutical composition in an amount ranging from about 8 mg to about 24 mg.
  3. The pharmaceutical composition according to claim 1, wherein methylcobalamin is present in the pharmaceutical composition in an amount ranging from approximately 0.5 mg to approximately 50 mg.
  4. The pharmaceutical composition according to claim 1, wherein methylcobalamin is present in the pharmaceutical composition in an amount ranging from approximately 0.5 mg to approximately 10 mg.
  5. The pharmaceutical composition contains azelastine or a pharmaceutically acceptable salt of azelastine in an amount ranging from approximately 8 mg to approximately 24 mg, and methylcobalamin in an amount ranging from approximately 0.5 mg to approximately 50 mg. The pharmaceutical composition according to claim 1.
  6. The pharmaceutical composition according to claim 2, wherein the pharmaceutically acceptable salt of azelastine is azelastine hydrochloride.
  7. The pharmaceutical composition according to claim 6, wherein methylcobalamin is present in the pharmaceutical composition in an amount ranging from approximately 0.5 mg to approximately 50 mg.
  8. The pharmaceutical composition according to claim 6, wherein azelastine hydrochloride is present in an amount ranging from approximately 8 mg to approximately 18 mg.
  9. The pharmaceutical composition according to claim 1, formulated as an oral pharmacopoeia.
  10. The pharmaceutical composition according to claim 9, wherein the oral pharmaceutical administration form is in solid or liquid form.
  11. The pharmaceutical composition according to claim 6, wherein azelastine hydrochloride is present in an amount ranging from approximately 8 mg to approximately 12 mg, and methylcobalamin is present in an amount ranging from approximately 1 mg to approximately 5 mg.
  12. A method for treating a patient with Alzheimer's disease or Parkinson's disease, Azelastine or a pharmaceutically acceptable salt of azelastine, Methylcobalamin, and an effective amount of a pharmaceutical composition comprising one or more pharmaceutically acceptable excipients, A method comprising the step of administering to a patient for a sufficient period of time to alleviate, reduce, prevent, and/or eliminate one or more symptoms of Alzheimer's disease or Parkinson's disease in the patient.
  13. The method according to claim 12, wherein the pharmaceutical composition is administered to a patient in an oral solid or liquid form once or twice a day, three times a day, or once every two, three, or four days.
  14. The method according to claim 13, wherein azelastine or a pharmaceutically acceptable salt of azelastine is present in the pharmaceutical composition in an amount ranging from about 8 mg to about 24 mg.
  15. The method according to claim 12, wherein methylcobalamin is present in the pharmaceutical composition in an amount ranging from approximately 0.5 mg to approximately 50 mg.
  16. The method according to claim 12, wherein the pharmaceutical composition is administered to the patient over a period of at least six weeks.
  17. The method according to claim 12, wherein methylcobalamin is present in the pharmaceutical composition in an amount ranging from approximately 0.5 mg to 10 mg.
  18. The method according to claim 12, wherein methylcobalamin is present in the pharmaceutical composition in an amount ranging from approximately 1 mg to approximately 10 mg.
  19. The pharmaceutically acceptable salt of azelastine is azelastine hydrochloride, which is present in the pharmaceutical composition in an amount ranging from approximately 8 mg to approximately 24 mg, and methylcobalamin is present in the pharmaceutical composition in an amount ranging from approximately 0.5 mg to approximately 50 mg. The method according to claim 12.
  20. The method according to claim 19, wherein methylcobalamin is present in the pharmaceutical composition in an amount ranging from approximately 0.5 mg to approximately 10 mg.

Description

Cross-reference of related applications [001] This application relates to U.S. Patent Application No. 16/382,88, filed on 12 April 2019. This is a continuation application in part of Patent No. 5, and the disclosure of the said patent application is incorporated herein by reference in its entirety. Technical field [002] The present invention relates to the field of practical medicine, namely the use of pharmaceutical compositions for treating Alzheimer's disease and Parkinson's disease. More specifically, the present invention relates to novel combinations of compounds that can effectively treat Alzheimer's disease (AD) and Parkinson's disease (PD). [003] Alzheimer's disease (AD) is a progressive chronic neurodegenerative disease that usually begins slowly and gradually worsens over time. AD is the most common cause of dementia in older adults. Dementia is a decline in cognitive function, namely thinking, memory, and logical thinking, as well as behavioral abilities, to the extent that it interferes with a person's daily life and activities. In the early stages of AD, memory decline is gradual, but in the later stages of AD, individuals lose the ability to continue a conversation and to respond to their environment. If left untreated, AD eventually leads to death. The rate of progression can vary, but the typical life expectancy after diagnosis is 3 to 9 years. [004] Neuropathologically, AD is characterized by the accumulation of amyloid-beta protein (Aβ) in senile plaques and neurofibrillary tangles of hyperphosphorylated tau protein (p-tau). The majority of current evidence identifies Aβ accumulation as the primary causative factor of sporadic AD. To date, all promising approaches to reduce Aβ or p-tau levels, including mechanisms such as inhibition of Aβ or p-tau production, reduction of soluble Aβ levels, and enhancement of Aβ or p-tau clearance from the CNS, have not shown desirable results in their clinical trials. While the development of Aβ-based treatments is logically derived from known Aβ mechanisms, many factors may limit the effectiveness of such treatments when applied individually. More importantly, however, many other potential mechanisms may be important causative factors in AD. Such non-Aβ mechanisms may play an even larger or possibly synergistic role as the disease progresses. Therefore, the parallel application of neuroprotective strategies is likely to play a significant role in delaying the onset of AD and slowing its progression. [005] Homocysteine is a sulfur-containing amino acid involved in essential metabolic pathways, including methylation. Elevated blood homocysteine is a marker of genetic disorders and vitamin B12 deficiency. Elevated homocysteine is associated with vascular diseases, neuropsychiatric disorders, stroke, silent infarction, and neurovascular ischemic diseases, including white matter lesions. Studies have linked homocysteine to the neurotoxicity of amyloid and glutamate, and to cognitive impairment and AD. For example, elevated homocysteine induces loss of hippocampal neurons in transgenic mice with amyloid deposition in the brain. Studies have also demonstrated a relationship between plasma homocysteine levels and AD and cognitive function in individuals without dementia. This relationship spans the normal range of homocysteine levels. Reducing homocysteine levels can be readily achieved with high doses of vitamin B12 and may be the most appropriate disease-modifying intervention in AD. [006] Methylcobalamin, one of the two active forms of the four vitamin B12 vitamers, is most effective in uptake by neuronal organelles compared to the other analogs. Therefore, methylcobalamin combined with azelastine may provide a better treatment option for neurological disorders such as AD. [007] On the other hand, the genetic, cellular, and molecular changes associated with AD support the evidence that activated immune and inflammatory processes are part of the disease. Furthermore, epidemiological studies have shown significant benefits of long-term use of NSAIDs. Thus, it is generally accepted that AD is partly an inflammatory disease and that inhibiting inflammation is an option for treating AD. [008] Inflammation is clearly occurring in pathologically vulnerable areas of the AD brain, which is accompanied by the full complexity of local peripheral inflammatory responses. Peripherally, degenerated tissue and deposition of highly insoluble abnormal substances are conventional inflammatory stimuli. Similarly, in the AD brain, damaged neurons and neurites, as well as deposition of highly insoluble amyloid-beta peptides and neurofibrillary tangles, provide clear inflammatory stimuli. These stimuli arise separately, are microlocalized, and are present from the early preclinical to the late stages of AD, and the local upregulation of complement, cytokines, acute-phase reactants, and other inflammatory mediators also arises separately, is microlocalized, and is chronic. With lon