Low pH Insulin Formulation for Precipitation Prevention
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Solution Overview
Problem
Current insulin therapies require multiple daily injections for diabetes management, with limitations in mixing different insulin types due to precipitation issues, leading to increased burden on patients.
Innovation Solution
Development of a combined fast or rapid acting-long acting insulin formulation at a low pH, using specific acids and chelating agents like EDTA to maintain solubility and enhance absorption, allowing for a single injection to cover both mealtime and basal insulin needs.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If insulin glargine is mixed with other short or rapid acting insulins, then the number of injections can be reduced, but the mixture causes glargine to precipitate prior to injection
Solution Approach 1:
The patent adjusts the pH of the rapid acting insulin component to be compatible with insulin glargine, preventing precipitation while maintaining solubility. This parameter change allows the mixture to remain stable and injectable, resolving the contradiction between reducing injection frequency and maintaining mixture reliability.
2Ease of operation
If NPH insulin is combined with short acting or rapid acting insulin analog, then the number of injections is reduced from five to four per day, but the mixture requires careful pH management to maintain stability
Solution Approach 1:
The patent carefully controls the pH parameters of the rapid acting insulin component to ensure compatibility with NPH insulin. By adjusting and maintaining the pH within a specific range, the mixture remains stable without precipitation, allowing reduction of injections from five to four per day while maintaining composition stability.
3Ease of operation
If a combined fast or rapid acting-long acting insulin formulation is developed, then the number of daily injections can be reduced to three, but the formulation requires low pH and chelating agents to prevent precipitation
Solution Approach 1:
The patent formulates the combined insulin preparation at a low pH (approximately 3.5-4.5) and includes chelating agents to bind metal ions that could cause precipitation. These parameter changes and additives enable the mixture of fast/rapid acting and long acting insulins without precipitation, reducing daily injections to three while managing formulation complexity through standardized pH control and chelation.
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
This formulation reduces the number of daily injections from four to three by providing adequate bolus and basal insulin coverage without causing hypoglycemia, demonstrated through in vitro and in vivo studies.
Implementation Method 1
the pH of the fast or rapid acting insulin is adjusted so that both rapid and long acting insulins remain soluble when they are mixed together
Implementation Method 2
any very rapid, rapid, or fast insulin can be combined with any intermediate, long or very long acting insulin at low pH, in the presence of a chelating agent
Data Source
AI summary
A combined rapid acting-long acting insulin formulation has been developed in which the pH of the rapid acting insulin is adjusted so that the long acting glargine remains soluble when they are mixed together. In the preferred embodiment, this injectable basal bolus insulin is administered before breakfast, provides adequate bolus insulin levels to cover the meal, does not produce hypoglycemia after the meal and provides adequate basal insulin for 24 hours. Lunch and dinner can be covered by two bolus injections of a fast acting, or a rapid acting or a very rapid acting insulin. As a result, a patient using intensive insulin therapy should only inject three, rather than four, times a day.