Therapeutic agent for nervous system disease
Inventors
Tanaka, Hiroyuki • Yoshikawa, Hideki • Mochizuki, Hideki • Murase, Tsuyoshi • Sasaki, Tsutomu • Baba, Kousuke • Iwahashi, Toru • Naiki, Mitsuru
Assignees
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Publication Number
US-11369626-B2
Publication Date
2022-06-28
Expiration Date
Abstract
A method of treating a central nervous system disease, the method including administering an agent including a therapeutically effective amount of vitamin B12 to a patient with a central nervous system disease to treat the central nervous system disease. This disclosure also relates to a method of promoting M2 macrophage/microglia induction, inhibiting M1 macrophage/microglia induction, and/or reducing the ratio of M1 macrophage/microglia to M2 macrophage/microglia in a patient in need thereof, the method including administering an agent including a therapeutically effective amount of vitamin B12 to the patient to promote M2 macrophage/microglia induction, inhibit M1 macrophage/microglia induction, and/or reduce the ratio of M1 macrophage/microglia to M2 macrophage/microglia. This disclosure also relates to a pharmaceutical product including vitamin B12.
Core Innovation
The invention relates to treating a central nervous system disorder by administering an agent comprising a therapeutically effective amount of vitamin B12, wherein the vitamin B12 is at least one selected from methylcobalamin, cyanocobalamin, hydroxocobalamin, sulfitocobalamin, adenosylcobalamin, and salts thereof. The method employs continuous intravenous administration for a period of time to modulate immune-cell phenotypes in the central nervous system.
The core mechanism described is that the effective amount of vitamin B12 promotes M2 macrophage/microglia induction and inhibits M1 macrophage/microglia induction. The disclosure frames this as shifting the M1/M2 balance by increasing M2 induction and reducing M1 induction, including reduction of the M1/M2 ratio.
The disclosure further states therapeutic rationales including anti-apoptotic and anti-necrotic effects and effects on axon outgrowth and nerve regeneration. The timing and administration approach include continuous intravenous administration with initiation after onset, including 12 to 24 hours after onset or within 12 hours, and the described outcomes involve central nervous system lesion and functional measures and macrophage/microglia marker changes.
Claims Coverage
The document contains one independent claim. The inventive coverage is based on vitamin B12 as a cobalamin agent delivered by continuous intravenous administration, where the vitamin B12 promotes M2 macrophage/microglia induction and inhibits M1 macrophage/microglia induction. Dependent claims further refine the treated disorder type, administration format, initiation timing window, and an outcome related to nerve regeneration.
Continuous intravenous vitamin B12 for central nervous system disorders with M2/M1 modulation
Administering, to a patient with a central nervous system disorder selected from a group consisting of a cerebrovascular disorder and central nerve injury caused by traumatic injury, pressure from a plaster cast, electrical injury, disk herniation, or radiation exposure, an agent comprising an effective amount of vitamin B12 (methylcobalamin, cyanocobalamin, hydroxocobalamin, sulfitocobalamin, adenosylcobalamin, or salts thereof) by continuous intravenous administration for a period of time, wherein the effective amount of vitamin B12 promotes M2 macrophage/microglia induction and inhibits M1 macrophage/microglia induction.
Cerebrovascular disorder subtypes treated with M2/M1-promoting vitamin B12
The method of treating a central nervous system disorder wherein the central nervous system disorder is a cerebrovascular disorder selected from cerebral infarction, cerebral hemorrhage, cerebral thrombosis, cerebral arteriosclerosis, or vascular dementia, using an effective amount of vitamin B12 that promotes M2 macrophage/microglia induction and inhibits M1 macrophage/microglia induction by continuous intravenous administration.
Spinal cord injury treatment with M2/M1-promoting vitamin B12
The method of treating central nerve injury caused by traumatic injury, pressure from a plaster cast, electrical injury, disk herniation, or radiation exposure, wherein the central nerve injury is spinal cord injury, by administering an agent comprising an effective amount of vitamin B12 (methylcobalamin, cyanocobalamin, hydroxocobalamin, sulfitocobalamin, adenosylcobalamin, or salts thereof) by continuous intravenous administration for a period of time, promoting M2 macrophage/microglia induction and inhibiting M1 macrophage/microglia induction.
Intravenous drip infusion continuous administration of vitamin B12
Providing that the agent comprising an effective amount of vitamin B12 is continuously administered to a patient via intravenous drip infusion, wherein vitamin B12 promotes M2 macrophage/microglia induction and inhibits M1 macrophage/microglia induction.
Initiation timing 12 to 24 hours after onset
Characterized by starting administration 12 to 24 hours after the onset of the central nervous system disorder, wherein an effective amount of vitamin B12 is continuously administered by intravenous administration to promote M2 macrophage/microglia induction and inhibit M1 macrophage/microglia induction.
Nerve regeneration promotion by vitamin B12 administration
Administering an effective amount of vitamin B12 to a patient, wherein the administration promotes nerve regeneration while promoting M2 macrophage/microglia induction and inhibiting M1 macrophage/microglia induction.
The claims cover a treatment method for central nervous system disorders using an effective amount of vitamin B12 delivered by continuous intravenous administration. The inventive concept is phenotype modulation of macrophage/microglia, specifically promoting M2 induction and inhibiting M1 induction. Dependent claims refine the disorder to particular cerebrovascular disorders or spinal cord injury, specify continuous intravenous drip infusion, add an initiation timing window, and include nerve regeneration promotion.
Stated Advantages
Promotes M2 macrophage/microglia induction and inhibits M1 macrophage/microglia induction (modulates M1/M2 balance).
Therapeutically beneficial effects are described including anti-apoptotic effects and anti-necrotic effects.
Effects on axon outgrowth and nerve regeneration are described.
Documented Applications
Treatment of central nervous system disorders, including cerebrovascular disorders (cerebral infarction, cerebral hemorrhage, cerebral thrombosis, cerebral arteriosclerosis, vascular dementia) and central nerve injury caused by traumatic injury, pressure from a plaster cast, electrical injury, disk herniation, or radiation exposure.
Treatment of spinal cord injury as a specific central nerve injury application.
Nerve regeneration promotion as an application outcome in the treated patient.
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