Transplantation therapies
Inventors
Alexander, Jonathan Steven • Carpenter, April C. • Castor, Trevor Percival
Assignees
Aphios Corp • Louisiana State University
Publication Number
US-10723744-B2
Publication Date
2020-07-28
Expiration Date
2028-12-31
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Abstract
Embodiments of the present invention are directed to methods and dosage forms for treating inflammation and rejection in transplantation injuries with Bryostatin-1, Bryostatin-1 analogs and pharmaceutically acceptable salts thereof.
Core Innovation
The invention is directed to methods and dosage forms for treating transplantation-mediated organ stress and rejection using Bryostatin-1, Bryostatin-1 analogs, or pharmaceutically acceptable salts thereof. These compositions are administered to reduce or prevent induced neutrophil trans endothelial migration, which plays a critical role in inflammatory damage and transplant rejection. The therapies are formulated in various dosage forms, including solid oral forms and parenteral formulations, optimized for effective delivery.
The problem addressed by the invention is the significant role of leukocyte-dependent injury—specifically neutrophil infiltration—in causing acute and chronic inflammation that leads to tissue damage and organ rejection following transplantation. Existing therapies inadequately address neutrophil infiltration, underscoring the need for novel solutions to suppress neutrophil-induced tissue injury in transplantation contexts.
The invention utilizes the activation of the protein kinase C delta (PKC-δ) isoform in endothelial cells as a mechanism to inhibit neutrophil trans endothelial migration. Administration of Bryostatin-1 and its analogs results in potent, long-lasting suppression of neutrophil migration, thereby protecting transplanted tissue from inflammatory injuries. Dosage forms are engineered to achieve target plasma concentrations, and both tissue-targeted and systemic treatments are described, including perfusion of organs with Bryostatin-1 prior to or after harvesting.
Claims Coverage
There is one independent claim in this patent, centered on the formulation and use of Bryostatin-1 or its analogs for treating transplantation injury.
Dosage form for treating transplantation injury with Bryostatin-1 or analogs to reduce or prevent neutrophil trans endothelial migration
The invention claims a dosage form comprising an effective amount of Bryostatin-1, Bryostatin-1 analog, or a pharmaceutically acceptable salt thereof to reduce or prevent induced neutrophil trans endothelial migration. - The dosage form is for administration to a human or animal in need thereof. - The dosage form contains saturated polyalkylene glycol glyceride. - The administration is intended to achieve a plasma concentration in the organ of about 10⁻⁷ M. The inventive feature centers on the formulation specifically designed for transplantation injury, targeting neutrophil trans endothelial migration.
The claims focus on a specialized dosage form utilizing Bryostatin-1 or its analogs, formulated to achieve effective plasma concentration and comprising saturated polyalkylene glycol glyceride for use in preventing or reducing neutrophil-mediated transplantation injury.
Stated Advantages
Provides tissue protection which is potent, lasting, and non-invasive, allowing rapid and economical treatment of diseases associated with transplantation injuries.
Enables reduction or prevention of neutrophil trans endothelial migration, which can reduce inflammation and rejection following organ transplantation.
Offers a method with an effect lasting up to 48 hours following short-term exposure, not requiring continuous presence of the drug.
Uses a therapy that has demonstrated safety in human and cancer patient studies, with no adverse effects observed at the proposed dosing range.
Documented Applications
Treatment and prevention of transplantation injury by reducing neutrophil trans endothelial migration in transplanted organs and tissues.
Perfusion of organs with Bryostatin-1 or its analogs prior to or immediately following harvesting for transplantation.
Intravenous, transdermal, intraperitoneal, and intra-alveolar instillation of Bryostatin-1 or analogs during active transplantation-related disease or during disease remission.
Prophylactic administration of Bryostatin-1 or analogs to limit the development of graft-versus-host disease (GVHD) following bone marrow or stem cell transplantation.
Interested in licensing this patent?