Insulin Combination for Flexible Mealtime Dosing

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Solution Overview

Problem

Current diabetes treatment methods, particularly for type 1 and type 2 diabetes, face challenges in achieving optimal glycemic control as measured by HbA1c levels, with existing insulin therapies often requiring fixed dosing schedules and lacking flexibility, which can lead to compliance issues and inadequate metabolic control.

Innovation Solution

A pharmaceutical composition comprising a combination of LysB29(Nε-hexadecandioyl-γ-Glu) des(B30) human insulin and Asp B28 human insulin administered once daily at the largest meal of the day, providing flexible dosing and improved glycemic control by decreasing HbA1c levels to 7.0% or less.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of operation

If fixed dosing schedules are used, then insulin delivery is simplified, but patient compliance deteriorates and glycemic control becomes inadequate

Engineering Contradiction:
Improvedosing simplicityVSAvoidpatient compliance
Core Design Contradiction:
Ease of operationVSReliability

Solution Approach 1:

The patent transforms the static, fixed dosing schedule into a dynamic system where insulin can be administered flexibly at meal times. The combination of long-acting and rapid-acting insulin components allows the regimen to adapt to varying meal patterns and patient needs, improving compliance while maintaining glycemic control.

Inventive Principle:
Principle #15Dynamics

Solution Approach 2:

The invention changes the dosing parameter from fixed time intervals to event-based administration (at largest meal). This parameter change allows patients to align insulin delivery with their actual eating patterns, improving both compliance and effectiveness without requiring complex monitoring.

Inventive Principle:
Principle #35Parameter changes

2Duration of action of stationary object

If long-acting insulin alone is used, then basal insulin requirement is covered, but postprandial glucose control deteriorates

Engineering Contradiction:
Improvebasal insulin coverage durationVSAvoidglycemic control precision
Core Design Contradiction:
Duration of action of stationary objectVSManufacturing precision

Solution Approach 1:

The patent merges two insulin components with different action profiles - long-acting insulin for basal coverage and rapid-acting insulin for postprandial control - into a single combination product. This merging allows simultaneous achievement of both prolonged duration of action and precise glycemic control.

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The insulin regimen is segmented into two functional components: a long-acting component for basal needs and a rapid-acting component for mealtime needs. This segmentation allows each component to optimize its specific function while working together to achieve comprehensive glycemic control.

Inventive Principle:
Principle #1Segmentation

3Manufacturing precision

If multiple daily injections are administered, then glycemic control improves, but treatment complexity increases

Engineering Contradiction:
Improveglycemic controlVSAvoidtreatment regimen complexity
Core Design Contradiction:
Manufacturing precisionVSDevice complexity

Solution Approach 1:

The patent combines multiple insulin functions into a single injection product, eliminating the need for separate basal and bolus injections. This merging maintains the glycemic control benefits of multiple-acting insulin while reducing the complexity of administration to a single daily injection.

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The combination insulin product serves multiple functions simultaneously - providing basal insulin coverage, postprandial glucose control, and flexible mealtime dosing - all in a single formulation. This multi-functionality reduces treatment complexity while maintaining comprehensive glycemic management.

Inventive Principle:
Principle #6Universality (Multi-functionality)

4Ease of operation

If insulin is administered at fixed times, then dosing schedule is simplified, but flexibility and patient adherence deteriorate

Engineering Contradiction:
Improvedosing schedule simplicityVSAvoiddosing flexibility
Core Design Contradiction:
Ease of operationVSAdaptability or versatility

Solution Approach 1:

The patent creates a dynamic dosing system where the timing of insulin administration is tied to the variable event of meal consumption rather than fixed clock times. This allows the regimen to adapt to changing patient schedules, travel, and lifestyle while maintaining simplicity in the dosing rule (administer at largest meal).

Inventive Principle:
Principle #15Dynamics

Data Source

PatentEP2844274B1Pharmaceutical composition
Publication Date: 2019.03.20 NOVO NORDISK AS
  • EP2844274B1 patent drawingFigure 1/2~2/2
  • EP2844274B1 patent drawing

AI summary

A combination comprising at least a first insulin-like compound and a second insulin-like compound for treating a condition or a diseasein a subject in need thereof where administration of insulin would be of benefit to said subject is described. The combination is administered in an amount to achieve a beneficial glycaemic control in said subject as determined by the levels of HbA1c in said subject after administration of said combination at the largest meal of the day for said subject; wherein said beneficial glycaemic control by said combination is superior to any glycaemic control achieved by an equivalent dose of IGlar in said subject as determined by the levels of HbA1c in said subject after administration of IGlar for said subject and/or wherein said beneficial glycaemic control by said combination comprises decreasing the levels of HbA1c in said subject to about 7 or less after administration of said combination at the largest meal of the day; wherein said first insulin- like compound is longer acting than the second insulin-like compound; wherein said combination is administered at the largest meal of the day for said subject; wherein said first insulin-like compound is at least a long acting insulin, preferably an ultra long acting insulin; wherein said first insulin-like compound is a derivative of a naturally occurring insulin or is an insulin analogue; and wherein said first insulin-like compound has a side chain attached to the a-amino group of the N-terminal amino acid residue of the B chain or to the ε-amino group of a Lys residue present in the B chain of the parent insulin, the side chain being of the general formula (I):- W-X-Y-Z.