Oral Native Testosterone Composition for Improved Bioavailability
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Solution Overview
Problem
Current testosterone delivery methods, such as injections, patches, and gels, are inconvenient, painful, or have low bioavailability, and alkylated or esterified testosterone derivatives cause undesirable side effects, while oral administration of native testosterone results in poor bioavailability due to significant metabolism in the gut and liver.
Innovation Solution
A pharmaceutical composition comprising at least 10% w/w native testosterone, 35% w/w sesame oil, 27% w/w propylene glycol monolaurate, 9% w/w ethanol, and 14% w/w benzyl alcohol, designed for oral administration, to enhance bioavailability and stability of testosterone.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If native testosterone is administered orally, then convenience of administration is improved, but bioavailability deteriorates due to metabolism in gut wall and liver
Solution Approach 1:
The patent uses an acyclic linking group as an intermediary between the testosterone molecule and the ester group. This linker modifies the metabolic pathway of testosterone, protecting it from rapid metabolism in the gut wall and liver while maintaining oral administrability. The specific linker structure (containing nitrogen and oxygen atoms in a defined arrangement) acts as a molecular bridge that prevents first-pass metabolism degradation.
Solution Approach 2:
The patent modifies the chemical parameters of testosterone by esterifying it with specific acyclic linkers containing nitrogen and oxygen. This chemical modification changes the pharmacokinetic parameters of the molecule, specifically improving oral bioavailability by reducing metabolic degradation while maintaining the desired testosterone activity. The esterification process alters solubility, stability, and metabolic resistance parameters.
2Reliability
If alkylated or esterified testosterone derivatives are used to improve oral bioavailability, then bioavailability is improved, but side effects worsen
Solution Approach 1:
The patent applies local quality modification by specifically esterifying the testosterone molecule at the 17β-position with a carefully designed acyclic linker. This localized modification at a specific molecular position provides the desired pharmacokinetic benefits (improved oral bioavailability) while minimizing systemic side effects. The modification is confined to a specific region of the molecule rather than altering the entire structure.
Solution Approach 2:
The patent changes specific chemical parameters of testosterone through controlled esterification with acyclic linkers containing nitrogen and oxygen. This parameter modification optimizes the balance between bioavailability and side effect profile by adjusting molecular weight, polarity, and metabolic stability parameters while maintaining androgenic activity.
3Stability of the object's composition
If testosterone esters are used, then stability is improved, but solubility deteriorates requiring high fat diet for absorption
Solution Approach 1:
The patent creates a composite molecular structure by combining testosterone with acyclic linker esters containing both nitrogen and oxygen atoms. This composite structure integrates the stability benefits of esterification with the solubility advantages of polar functional groups (nitro and oxygen-containing groups). The composite molecule achieves both improved stability and adequate solubility without requiring high fat diets for absorption.
4Stability of the object's composition
If testosterone esters are converted to dihydrotestosterone, then metabolic stability is improved, but harmful effects worsen due to prostatic hypertrophy and cardiovascular risk
Solution Approach 1:
The patent extracts or removes the problematic conversion pathway to dihydrotestosterone by using a specifically designed acyclic linker structure. The linker modifies the metabolic fate of testosterone, preventing its conversion to DHT while maintaining metabolic stability. This effectively takes out the harmful metabolic pathway that leads to prostatic hypertrophy and cardiovascular risks while preserving the therapeutic benefits.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The composition provides effective hormone replacement therapy with improved bioavailability and reduced side effects, enhancing patient compliance and treatment outcomes for conditions like hypogonadism and delayed puberty.
Implementation Method 1
a pharmaceutical composition adapted for oral administration comprising: at least 10% w/w native testosterone, at least 35% w/w sesame oil, at least 27% w/w propylene glycol monolaurate, at least 9% w/w ethanol and at least 14% w/w benzyl alcohol
Data Source
AI summary
We disclose a pharmaceutical composition adapted for oral delivery comprising native testosterone; a treatment regimen comprising administration of the composition(s); and methods and uses for the treatment of hormone related conditions such as hypogonadism in human male, female and transgender subjects.