Preparation and use of a composition for prevention and mitigation of the effects of radiation
Inventors
Compadre, Cesar M. • Breen, Philip • Aykin-Burns, Nukhet • Hauer-Jensen, Martin • Enriquez, Raul G. • Kharade, Sujay • Malagon, Omar • Ordonez, Yadira • Ojeda, Edgar • Thakkar, Shraddha • Pineda, E. Nathalie • Jones, Darin
Assignees
UNIVERSIDAD TECNICA PARTICULAR DE LOJA • US Department of Veterans Affairs • BioVentures LLC
Publication Number
US-10357474-B2
Publication Date
2019-07-23
Expiration Date
2034-09-15
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Abstract
Plant extracts, compositions, pharmaceutical compositions and methods of making and using the same are provided herein. The compositions comprise γ-tocotrienol (GT3) and δ-tocotrienol (DT3) in ratios wherein the DT3 is predominate. The compositions are useful for radioprotection and radiomitigation in subjects in need thereof.
Core Innovation
This invention provides plant extract compositions, pharmaceutical compositions, and methods of making and using said compositions, specifically comprising γ-tocotrienol (GT3) and δ-tocotrienol (DT3) in ratios where DT3 predominates. These compositions are useful for radioprotection and radiomitigation in subjects exposed to radiation. A method is described for preparing a composition with tocotrienols and low or absent tocopherols through extraction from plants such as annatto, followed by enrichment and purification to achieve effective radioprotective activity without toxicity.
The problem addressed is the difficulty in obtaining pure tocotrienols, which are naturally present only as complex mixtures with tocopherols, making them expensive and hard to concentrate for therapeutic use. Tocotrienols, notably GT3 and DT3, have demonstrated radioprotective effects not present in tocopherols, but available sources contain significant tocopherol amounts that may interfere with tocotrienol efficacy. Therefore, the invention aims to provide compositions enriched in tocotrienols with minimal tocopherol content to effectively prevent and mitigate radiation effects.
The compositions have a defined ratio of δ-tocotrienol to γ-tocotrienol between 2:1 and 10:1, preferably about 7:1, with total tocotrienol content ranging from 15% to 95% and tocopherol content significantly reduced, sometimes to undetectable levels. The methods enable preparation of uniform, standardized extracts, notably DG-3 derived from annatto seed oil via solvent extraction and chromatographic purification. Use of these compositions demonstrates synergistic radioprotective effects superior to individual tocotrienols, preserving cell viability and mitochondrial function following oxidative or radiation insults.
Claims Coverage
The patent includes one independent claim focusing on a method of treating a subject requiring radioprotection or treatment of radiation exposure using a specific tocotrienol composition. The main inventive features extracted relate to the composition's content, ratio, origin, and method of preparation, as well as pharmaceutical formulation and dosage.
Method of treating radiation exposure with a specific tocotrienol composition
Administering an effective amount of a tocotrienol composition comprising δ-tocotrienol and γ-tocotrienol in a ratio between 2:1 and 10:1 to a subject in need of a radioprotectant or for treatment of radiation exposure.
Preferred tocotrienol ratio in composition
The composition comprises δ-tocotrienol and γ-tocotrienol in a ratio specifically between 5:1 and 9:1, optimizing the predominance of δ-tocotrienol.
Annatto seed extract as a source of tocotrienols
The tocotrienol composition can be an annatto seed extract prepared by extracting oil from annatto seeds and enriching δ-tocotrienol and/or γ-tocotrienol from the annatto seed oil.
Composition characterized by tocotrienol and tocopherol content
The composition has a total tocotrienol content between 15% and 95%, at least 50% in some embodiments, and a tocopherol content less than 5%, preferably less than 1%, enhancing radioprotective efficacy.
Pharmaceutical composition and dosage form
The tocotrienol composition is formulated as a pharmaceutical composition with a pharmaceutically acceptable carrier, capable of providing a dosage form with at least 1 gram of total tocotrienols.
The claims protect a method of treating radiation exposure using compositions comprising δ-tocotrienol and γ-tocotrienol with defined ratios and purity, especially annatto seed extracts prepared by specific extraction and enrichment methods. The claims also cover pharmaceutical formulations with controlled tocotrienol content and minimal tocopherols, ensuring effective radioprotection and mitigation.
Stated Advantages
The compositions exhibit effective radioprotective and radiomitigative activity without toxicity.
The tocotrienol compositions show synergistic effects greater than individual tocotrienol constituents.
The DG-3 standardized extract protects cells from oxidative stress and radiation-induced mitochondrial dysfunction, preserving cell viability and mitochondrial respiration.
Compositions have reduced tocopherol content to avoid interference with tocotrienol bioavailability and bioactivity.
The compositions provide complete (100%) radiation protection in mice exposed to lethal doses of ionizing radiation.
Documented Applications
Radioprotection and radiomitigation for subjects exposed to ionizing radiation, including patients undergoing radiation therapy or individuals exposed to nuclear accidents.
Treatment of radiation exposure through administration as a radioprotectant prior to exposure or as a radiomitigator after exposure.
Use as antioxidant, anti-inflammatory, immunoregulatory, antithrombotic, anti-atherogenic, hypocholesterolemic agents, and HMG-CoA reductase inhibitors.
Treatment of diseases and conditions including cancer, cardiovascular diseases, elevated cholesterol or lipoproteins, age-related macular degeneration, cataracts, glaucoma, chronic pain, chronic fatigue syndrome, fever, edema, diabetes mellitus, signs of aging, rheumatoid diseases, septic shock, inflammatory and autoimmune diseases, and Alzheimer's disease.
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