High-Potency Pancreatin Compositions Using Solvent Purification
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Solution Overview
Problem
Existing pancrelipase products for treating exocrine pancreatic insufficiency (EPI) are less pure, leading to high pill load, microbial contamination risks, and lower efficacy due to low enzyme activity and presence of inactive materials, which also interfere with purification techniques.
Innovation Solution
Development of high activity pancreatin (HA-pancreatin) enzymes with increased lipase activity (e.g., 120-500 USP IU/mg) through a solvent treatment process using specific solvents with Hildebrand solubility parameters between 28 and 45 (MPa)0.5, reducing unnecessary biological components and enabling smaller, more convenient dosage forms.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Manufacturing precision
If traditional enzyme extraction procedures are used to produce pancrelipase products, then the production process is simple and well-established, but the enzyme purity is low (as little as 25% protein) and the active enzyme content is low (less than 0.5% active lipase)
Solution Approach 1:
The patent applies extraction by selectively precipitating inactive materials and contaminants from the crude enzyme extract using specific solvents (acetone, ethanol, isopropanol) at controlled temperatures and pH levels. This removes unwanted components while preserving the active pancreatic enzymes, thereby increasing enzyme purity from 25% to potentially much higher concentrations without requiring complete reconstruction of the production process
Solution Approach 2:
The patent employs parameter changes by adjusting pH levels, temperature conditions, and solvent concentrations during the purification process. For example, adjusting pH to specific ranges and using solvents at particular concentrations allows selective precipitation of inactive materials while maintaining enzyme activity, thus improving purity without overly complicating manufacturing
2Quantity of substance
If traditional pancrelipase products with low enzyme activity are used, then the formulation is simple, but the pill burden is high (4-9 relatively large capsules per meal) and patient adherence decreases
Solution Approach 1:
The patent increases enzyme activity concentration by changing the purity parameters of the enzyme extract through purification processes. This concentrates the active enzymes into a smaller volume, allowing the same therapeutic dose to be delivered in fewer, smaller capsules, directly reducing pill burden and improving patient compliance
3Reliability
If traditional enzyme extracts with high inactive material content are used, then the production cost is lower, but the risk of microbial and viral contamination increases and the material interferes with bio-burden reduction techniques
Solution Approach 1:
The patent removes inactive materials and potential contaminants through selective precipitation using solvents like acetone, ethanol, or isopropanol. This extraction process separates active enzymes from inactive proteins and other contaminants, reducing microbial and viral contamination risks while enabling more effective bio-burden reduction techniques without excessive loss of active enzyme material
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
HA-pancreatin provides higher enzyme activity, reduces pill burden, minimizes microbial contamination, and allows for safer, more effective treatment of EPI with smaller dosage forms, including single pills and liquid suspensions, suitable for various administration methods.
Implementation Method 1
treating pancreatin with a solvent, wherein said solvent has Hildebrand solubility parameter (SP) comprised between 28 and 45 (MPa)0.5
Data Source
AI summary
The present invention provides high potency pharmaceutical compositions comprising high activity pancreatin enzymes. The invention is also directed to a process of producing HA-pancreatin enzymes and its compositions or dosage forms, and methods for their use.