Use of Targeted Nitroxide Agents in Bone Healing
The invention provides compositions and methods for accelerating bone healing and growth. The compounds use a nitroxide-containing group attached to a mitochondria-targeting group to increase the scavenging of reactive oxygen species and prevent cell death.
Description
The core technology involves compositions containing a mitochondria-targeting group and a nitroxide-containing group. The compounds are designed to target the nitroxide to the mitochondria, which increases the scavenging of reactive oxygen species (ROS) and prevents cell death. The compounds can also be cross-linked into dimers without losing activity. The patent provides detailed methods for synthesizing these compounds, including the use of an organozirconium catalyst to produce an alkene and a condensation reaction to attach a nitroxide-containing group. The patent highlights specific compounds such as JP4-039 and XJB-5-131, which are described as being more potent than previous nitroxide compounds due to their mitochondrial targeting.Applications
- Treatment of Bone Injuries: Accelerating bone healing, growth, or repair following injury or damage.- Traumatic Injuries: Used as a pre-treatment or post-injury therapeutic to prolong patient survival after massive blood loss.
- Radioprotection: Ameliorating irradiation-induced delays in bone healing.
- Other Conditions: Potentially beneficial for other conditions associated with tissue hypoperfusion, such as stroke and myocardial infarction.
- Drug Development: The test system and drug class can be of value in developing new small molecule radioprotectors and radiomitigators.
Advantages
- Accelerates bone healing and growth.- The targeted delivery to mitochondria increases the efficacy of reactive oxygen species scavenging.
- Significantly more potent than non-targeted compounds, requiring a much smaller dose to achieve a beneficial effect.
- Extends the window of time for treatment in patients who have suffered massive blood loss.
- Can be formulated into various pharmaceutical dosage forms, including intravenous solutions, oral tablets, topical ointments, and transdermal patches.
Invention Readiness
The targeted nitroxide compound (JP4-039) showed a beneficial effect, prolonging the survival of rats subjected to massive blood loss and demonstrating greater potency than another commercially available compound (TEMPOL). Further studies are being planned to investigate the effects of administering JP4-039 after wound healing, after irradiation, and after cord blood injection.IP Status
https://patents.google.com/patent/US8748369B2Related Publication(s)
Gokhale, A., Rwigema, J.C., Epperly, M.W., Glowacki, J., Wang, H., Wipf, P., ... & Greenberger, J.S. (2010). Small molecule GS-nitroxide ameliorates ionizing irradiation-induced delay in bone wound healing in a novel murine model. In vivo (Athens, Greece), 24(4), 377-85.