Oral Methylene Blue Compounds Using Reduced LMT for Methaemoglobinaemia
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Solution Overview
Problem
Current treatments for methaemoglobinaemia, such as intravenous methylthionium chloride, can cause acquired methaemoglobinaemia and are inconvenient, while oral hydromethylthionine compounds at high doses increase methaemoglobin levels, posing safety concerns.
Innovation Solution
Oral administration of low to moderate doses of LMTX compounds, including LMT, to convert Fe3+ to Fe2+ in methaemoglobin, reducing methaemoglobin levels without causing hypoxia, suitable for both hereditary and acquired forms of the condition.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If intravenous methylthionium chloride is used to treat methaemoglobinaemia, then methaemoglobin levels are reduced, but acquired methaemoglobinaemia is caused
Solution Approach 1:
The patent changes the chemical form of the methylthioninium compound from the oxidised MT+ form (methylene blue) to the reduced LMT form (hydromethylthionine). This parameter change in oxidation state allows the compound to reduce Fe3+ to Fe2+ in methaemoglobin without causing the paradoxical formation of acquired methaemoglobinaemia that occurs with MT+ administration.
2Ease of operation
If oral hydromethylthionine compounds are administered at high doses, then convenient oral treatment is provided, but methaemoglobin levels increase
Solution Approach 1:
The patent identifies a specific dose range parameter (4-60 mg MT per day) that resolves the contradiction between oral convenience and safety. Within this dosage window, the LMTX compound effectively reduces methaemoglobin levels through oral administration without causing the harmful increase in metHb levels that occurs at higher doses.
3Quantity of substance
If LMTX compounds are administered to reduce methaemoglobin, then oxygen saturation improves, but hypoxia may occur as a side effect
Solution Approach 1:
The patent optimizes the dosage parameters to fall within 4-60 mg MT per day, which provides sufficient reduction of methaemoglobin levels to improve oxygen saturation while remaining below the threshold that would cause hypoxia. This precise parameter control resolves the contradiction between therapeutic efficacy and avoidance of hypoxic side effects.
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
Provides a safe and convenient oral treatment option for methaemoglobinaemia, effectively reducing methaemoglobin levels and improving oxygen saturation in patients, with minimal side effects on methaemoglobin levels, even at higher doses.
Implementation Method 1
LMT is the active species at the heme site of action where it facilitates the transfer of an electron from LMT to Fe3+, reducing it to Fe2+ and oxidising LMT to MT+ in the process
Implementation Method 2
The methylthionine (MT) moiety can exist in the oxidised MT+ form (in MTC) and in the reduced or 'leuco' form hydromethylthionine (LMT) form
Data Source
AI summary
The invention provides novel methods of treating methaemoglobinaemia orally in a subject, which methods comprise orally administering to said subject a methylthioninium (“MT”) containing salt of the following formula: wherein each of HnA and HnB (where present) are protic acids which may be the same or different, and wherein p=1 or 2; q=0 or 1; n=1 or 2; (p+q)×n=2, or a hydrate or solvate thereof. The administration should provide a total daily oral dose of 4 mg to 60 mg of MT to the subject per day.