Telomerase Activator Compounds Oral Bioavailability
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Solution Overview
Problem
Existing telomerase activators, such as cycloastragenol, have limited bioavailability when administered orally, leading to reduced effectiveness as telomerase activators in certain mammalian species due to low uptake or high metabolism, necessitating the development of new compounds with improved oral bioavailability and longer half-life.
Innovation Solution
Development of specific chemical compounds, including those of formula I, which are potent telomerase activators and can be effectively administered orally across various mammalian species, with formulations that enhance telomerase activity in cells, such as keratinocytes and PBMCs, by at least 50% as measured in a TRAP assay.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing telomerase activators (e.g., cycloastragenol) are administered orally, then telomerase activity can be increased in cells, but bioavailability is limited due to low uptake or high metabolism
Solution Approach 1:
The patent modifies the chemical structure of cycloastragenol by changing functional groups (e.g., converting hydroxyl groups to other moieties) to improve oral bioavailability while maintaining telomerase activation capability. This directly addresses the contradiction by altering molecular parameters to enhance absorption and reduce metabolism.
Solution Approach 2:
The patent develops composite formulations combining cycloastragenol or its derivatives with carrier materials or delivery systems to enhance oral bioavailability. These composite structures protect the active compound from metabolic degradation and improve uptake, thereby resolving the contradiction between effectiveness and bioavailability.
2Reliability
If existing telomerase activators are administered orally, then telomerase activity increases, but half-life is short due to rapid metabolism
Solution Approach 1:
The patent modifies chemical parameters of cycloastragenol (e.g., adding bulky groups, changing functional groups) to reduce metabolic rate and extend half-life. These structural changes make the molecule more resistant to enzymatic degradation while preserving telomerase activation, directly resolving the effectiveness-half-life contradiction.
Solution Approach 2:
The patent employs prodrug approaches where cycloastragenol is converted to a protected form that is metabolized in vivo to release the active compound. This beforehand protection against metabolism extends the duration of action while ensuring effective telomerase activation occurs when the active form is released.
Data Source
AI summary
The present invention relates to methods and compositions for increasing telomerase activity in cells. Such compositions include pharmaceutical formulations. The methods and compositions are useful for treating diseases subject to treatment by an increase in telomerase activity in cells or tissue of a patient. They are also useful for enhancing replicative capacity of cells in culture, as in ex vivo cell therapy and for enhancing proliferation of stem and progenitor cells.