Methods for Treating Traumatic Brain Injury
US20250057801A1
Abstract
A method for treating traumatic brain injury include administering to a patient having traumatic brain injury and in need of treatment an effective amount of a composition comprising resveratrol triacetate or esterified resveratrol. The traumatic brain injury may be a penetrating brain injury.
Description (excerpt)
This application claims priority to U.S. Ser. No. 63/532,457 filed in the US Patent and Trademark Office on 14 Aug. 2023, the entirety of which is incorporated herein by reference. FIELD OF INVENTION The present invention is directed to methods for treating traumatic brain injury with a composition comprising resveratrol triacetate (triacetyl resveratrol or RES). In a specific embodiment, the traumatic brain injury may be a penetrating traumatic brain injury. BACKGROUND OF INVENTION Resveratrol is a natural compound present in grapes, mulberries, peanuts, and in several other plants. This compound has low water solubility and short half-life (in 8-14 minutes). Therefore, many strategies have been employed to increase its water solubility and extend half-life, so that the drug remains longer in circulation to achieve higher therapeutic efficacy. Triacetyl resveratrol is formulated by addition of acetyl moieties to resveratrol with the result that it displays greater bioavailability (absorption), solubility and potential to extend half-life compared to the parent compound. Thus, triacetyl resveratrol (3′,5′,4′-tri-o-acetyl resveratrol) is a cell-permeable and stable resveratrol prodrug. It has been hypothesized that the three acetate moieties may be able to provide energy to an injured site; whereas, resveratrol may be able to provide other cytoprotective effects (e.g., antioxidant, anti-inflammatory, and antiapoptotic) after brain trauma. Triacetyl resveratrol can be easily digested to the parent compound resveratrol by esterase and distributes rapidly to tissues within the body. Studies have shown that resveratrol has several beneficial effects that include decreasing inflammation, reducing cell death activity, anti-cancer activity, and activity as a powerful antioxidant to mitigate the effects of oxidative stress. Oxidative stress is an imbalance of free radicals and antioxidants in the body, more specifically in the mitochondria (intracellular organelle), which can further lead to cell and tissue damage. Among the factors leading to traumatic brain injury (TBI) outcome are biochemical cascades which occur in response to primary and secondary injury. These mechanisms elevate oxidative stress, and decrease endogenous antioxidant level, that can result in neural dysfunction and death. Military service members and veterans are at risk of traumatic brain injury from explosions experienced during combat or training exercises. TBI is one of the signature injuries during military operations that lack approved treatment. Depending on the severity of the brain injury, a person with TBI may experience a change in consciousness that can range from being dazed and confused to losing consciousness. Secondary injury is progressive following direct insult. Mitochondrial dysfunction contributes to TBI pathogenesis. Currently, neuroprotective therapeutic intervention for acute TBI is an unmet need. Resveratrol has been the subject of a study; however, there has been no clinical study for resveratrol derivatives or triacetyl resveratrol for treating traumatic brain injury (TBI). SUMMARY OF INVENTION The present invention provides in a first embodiment a method for treating traumatic brain injury comprising administering to a patient having traumatic brain injury and in need of treatment an effective amount of a composition comprising resveratrol triacetate (RES). The invention provides in a second embodiment further to any of the previous embodiments a method for treating traumatic brain injury comprising administering to the patient about 50 mg/kg/day to about 150 mg/kg/day of resveratrol triacetate. The invention provides in a third embodiment further to any of the previous embodiments a method for treating traumatic brain injury wherein the administering is by an oral supplement or additive. The administering may also be by a nasal spray or intramuscular injection. The invention provides in a fourth embodiment further to any of the previous embodiments a method for treating traumatic brain injury wherein the administration initiated within about 15 minutes to about 60 minutes, and may continue to be given once daily for a sub-acute period (e.g., 0-14 days) after a traumatic brain injury event. The invention provides in a fifth embodiment further to any of the previous embodiments a method for treating traumatic brain injury further comprising administering to the patient an effective amount o
Filing details
- Inventors
- Jignesh D. Pandya
- Assignee
- The Government Of The United States, As Represented By The Secretary Of The …
- Filed
- Aug 5, 2024
- Granted
- Application pending
Bibliographic data and excerpted text sourced from Google Patents (public record) as part of IP TechMatch's current-filings monitor. This filing is not part of the 2019 historical archive. For the authoritative full text, drawings, and legal status, see the source links above or consult USPTO records directly.