4503
Platform Technology for Efficient Oral Administration of Peptides for Therapeutic Purposes
Gilon Chaim, HUJI, Faculty of Science, The Institute of Chemistry
Hoffman Amnon, HUJI, School of Medicine - IMRIC, School of Pharmacy- Institute for Drug Research
Hoffman Amnon, HUJI, School of Medicine - IMRIC, School of Pharmacy- Institute for Drug Research
Background
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Peptides are key players in a variety of physiological and pathological processes and play very important roles in modulating various cell functions.
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One of the most important challenges developing peptide drugs is the lack of appropriate physicochemical properties that enables the absorption through biological membranes.
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Currently, most peptide drugs are administered parentally due to their poor intestinal permeability attributed to their hydrophilicity mainly due to charged groups.
Our Innovation
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A novel method called Lipophilic Prodrug Charge Masking (LPCM) that enhance the intestinal permeability and the oral bioavailability of charged peptides
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Significantly increased permeability rate of most peptides compared to the respective unmasked peptides.
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Brings into the systemic blood circulation the parent drug.
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Converts active peptides to orally therapeutic treatment
Technology
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The major challenges in peptide membrane permeability via passive diffusion include the peptide’s high polarity, charge and hydrogen bond potential.
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In the LPCM method, synthetic methods for the conversion of peptides, peptidomimetic and peptide drugs into their lipophilic prodrug were demonstrated.
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Charged masked peptide prodrugs were synthesized and masked with urethane/ ester type lipophilic pro-moiety. The prodrug enhanced intestinal permeability allowed its absorption to the blood stream where esterases removed the pro-moiety to regenerate the original peptides.
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The LPCM method shifts the mechanism of intestinal permeability of the charged peptides from para-cellular to trans-cellular pathway of their lipophilic prodrug
Fig. 1: Principle of the LPCM method
Opportunity
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New oral peptides/peptidomimetics medications
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Chronic treatment with good patient compliance
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Currently being studied and tested for RGD containing peptide
Patent Status
Published US 2020/0283483 A1