Polypeptide Derivative Fatty Acid Modification Half-Life
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Solution Overview
Problem
Polypeptide/protein drugs with molecular weights less than 20 kDa have short half-lives due to rapid degradation and excretion, requiring frequent high-dose administrations, which can lead to side effects and increased treatment costs.
Innovation Solution
A polypeptide derivative is created by modifying polypeptides such as insulin, GLP-1, and PTH with a fatty acid group linked to a lysine site via a non-covalent bond, increasing their molecular weight and stability, thereby prolonging their half-life and reducing clearance.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of manufacture
If polypeptide/protein drugs with molecular weight less than 20 kDa are used, then they can be easily synthesized and maintained, but they have short half-lives due to rapid glomerular filtration and protease degradation
Solution Approach 1:
The patent combines the polypeptide drug with a carrier molecule (such as albumin or polyethylene glycol) to form a conjugate. This merging increases the molecular weight of the drug complex, reducing glomerular filtration rate and protease degradation, thereby extending the half-life while maintaining the original polypeptide's therapeutic activity
Solution Approach 2:
The invention creates a composite structure where the polypeptide drug is covalently or non-covalently bound to a carrier molecule. This composite material possesses properties of both components: the therapeutic activity of the polypeptide and the prolonged circulation time provided by the carrier, effectively resolving the contradiction between ease of manufacture and duration of action
2Reliability
If high-dose frequent injections are administered to achieve therapeutic effect, then therapeutic efficacy is maintained, but patient suffering and treatment costs increase
Solution Approach 1:
The patent creates a dynamic release system where the drug is continuously and slowly released from the conjugate structure. This dynamic release maintains therapeutic drug levels over an extended period, reducing the frequency of injections from daily to weekly or monthly administrations, thereby improving patient convenience while maintaining therapeutic efficacy
Solution Approach 2:
The conjugate structure enables continuous drug delivery to the target site. The sustained release mechanism ensures that therapeutic action is maintained continuously over time rather than in discrete pulses, reducing the need for frequent re-administration and improving patient compliance
3Reliability
If frequent high-dose injections are given, then therapeutic effect is achieved, but side effects and treatment costs increase
Solution Approach 1:
The sustained release conjugate system provides dynamic, controlled drug delivery that maintains therapeutic levels without excessive peaks. This reduces the incidence of dose-related side effects while maintaining reliable therapeutic effect, as the drug is released gradually rather than in large repeated doses
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 modified polypeptide derivatives exhibit significantly prolonged half-lives while maintaining biological activity, reducing the frequency of injections and side effects, and providing a stable, long-term therapeutic effect for conditions like diabetes and osteoporosis.
Implementation Method 1
a non-covalent bond between the fatty acid and albumin
Data Source
AI summary
Provided are a polypeptide derivative and a preparation method thereof. Specifically, a polypeptide derivative is provided. Experimental results show that the polypeptide derivative has a significantly prolonged half-life while maintaining biological activity. The preparation method of the polypeptide derivative and its use in therapy are also disclosed.