Insulin Formulation Rapid Absorption via Zinc Chelation
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Solution Overview
Problem
Current insulin therapies, including rapid-acting insulin analogs, fail to replicate the natural first-phase insulin release, leading to inadequate insulin levels at meal initiation and excessive insulin between meals, resulting in hyperglycemia and hypoglycemia, and are inconvenient due to slow absorption and injection requirements.
Innovation Solution
Development of injectable insulin formulations combining human insulin with a chelator like EDTA and a dissolution agent such as citric acid, which rapidly dissociate into monomeric or dimeric forms, enhancing absorption and mimicking the natural insulin time-action profile by rapid subcutaneous administration.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Speed
If rapid-acting insulin analogs are used, then insulin is delivered to blood faster than natural first-phase release, but insulin levels still peak too late (80-100 minutes) and do not replicate natural physiology
Solution Approach 1:
The patent changes the molecular state parameter of insulin from hexameric to monomeric form through pH adjustment and zinc chelation, enabling rapid absorption that replicates natural first-phase insulin release timing
Solution Approach 2:
The patent prepares insulin in a pre-dissociated monomeric state before injection using low pH and chelators, so that upon subcutaneous administration, the insulin is immediately available for rapid absorption without requiring dissociation time
2Stability of the object's composition
If conventional insulin formulations are administered, then insulin is delivered to blood slowly (80-100 minutes peak), but this causes inadequate insulin levels at meal initiation leading to hyperglycemia
Solution Approach 1:
The patent adjusts pH to physiological range (6.8-7.4) and uses zinc chelators to change insulin from stable hexameric form to rapidly absorbable monomeric form, achieving both stability and rapid absorption
Solution Approach 2:
The patent introduces zinc chelators as intermediary substances that bind zinc ions, preventing hexamer formation and promoting monomeric insulin structure for rapid absorption
3Reliability
If excessive insulin is secreted between meals, then blood glucose control is achieved, but this causes weight gain and pancreatic deterioration
Solution Approach 1:
The patent creates a periodic insulin delivery pattern that mimics natural physiology: rapid first-phase release at meal times followed by lower second-phase levels, preventing excessive between-meal insulin secretion
Solution Approach 2:
The patent's rapid-acting formulation allows the body's natural glucose feedback mechanisms to regulate insulin secretion more effectively, reducing inappropriate insulin release that causes weight gain and pancreatic stress
4Reliability
If insulin is administered via injection, then insulin delivery is achieved, but patient compliance is poor due to inconvenience and pain
Solution Approach 1:
The patent formulates insulin at physiological pH with chelators to enable rapid absorption, allowing smaller, less frequent injections that reduce patient burden while maintaining effectiveness
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 formulations achieve rapid onset of action, peaking within 15-30 minutes, providing better glycemic control, reducing hypoglycemic events, and improving patient compliance through faster absorption and more physiological insulin delivery.
Implementation Method 1
The formulations contain insulin in combination with a chelator and dissolution agent
Implementation Method 2
The formulations contain insulin in combination with a chelator and dissolution agent
Implementation Method 3
These formulations are rapidly absorbed into the blood stream when administered by subcutaneous injection
Data Source
AI summary
Injectable insulin formulations with improved stability and rapid onset of action are described herein. The formulations may be for subcutaneous, intradermal or intramuscular administration. In the preferred embodiment, the formulations are administered via subcutaneous injection. The formulations contain insulin in combination with a chelator and dissolution agent, and optionally additional excipients. In the preferred embodiment, the formulation contains human insulin, a zinc chelator such as EDTA and a dissolution agent such as citric acid or sodium citrate. These formulations are rapidly absorbed into the blood stream when administered by subcutaneous injection. In the preferred embodiment, the insulin is provided as a clear liquid, neutral pH, in a multi-use sterile vial. In an alternative embodiment, the insulin is provided as a powder in a sterile vial. This is mixed with a diluent containing a pharmaceutically acceptable carrier, such as water, a zinc chelator such as EDTA and a dissolution agent such as citric acid shortly before or at the time of administration. In another embodiment, the insulin is stored as a frozen mixture, ready for use upon thawing.