Highly Efficient Intestinal Delivery and Absorption DDS Peptide

Oral DDS technology using cyclic peptides of D-amino acids that can reach the small intestine while suppressing degradation in the digestive tract and allowing highly efficient permeation through the intestinal epithelium.


  • Less susceptible to degradation by digestive enzymes, enabling highly efficient delivery of biopolymer preparations to the small intestine.
  • Highly efficient permeation of the peptide through the intestinal epithelium has been confirmed by experiments using model animals.
  • Low cytotoxicity and safety.
  • Potential to convert existing parenteral drugs, such as home self-injection drugs, into orally administered drugs.

Technology Overview & Background

Oral administration of drugs is the most popular route of administration because it is safe, simple, and non-invasive.  However, in the case of administration of biopolymers such as peptides and nucleic acids, there are problems such as degradation by enzymes in the digestive tract after oral administration and inadequate efficacy due to low intestinal absorption of the high molecular weight.

The researchers identified several cyclic peptides that permeate the intestinal epithelium in the small intestine with high efficiency by combining the M13 phage display method with the Caco-2 cell permeability experimental system, which mimics the human intestinal tract.  Furthermore, they obtained the most efficient intestinal absorption peptide, which is named DNP peptide, from these candidate peptides through experiments using mice.  In addition, they also developed “D-DNP” peptides using D-amino acids to make them less likely to be degraded in the gastrointestinal tract.  The D-DNP peptide was combined with recombinant insulin, an example of an existing drug that is considered difficult to administer orally, and administered orally to mice, which experimentally confirmed its high absorption in the small intestine.


  • Caco-2 cell monolayer uptake assay and mouse intestinal absorption assay (in situ closed-loop method) showed that DNP peptide was approximately 37- and 620-fold more permeable than the control, respectively.
  • When D-DNP peptide was complexed with insulin monomer or insulin hexamer used in existing insulin formulations and orally administered to mice, both complexes increased the concentration of insulin in portal plasma and significantly decreased blood glucose levels. These results showed that insulin reached the small intestine without being degraded in the digestive tract and also permeated the intestinal epithelium.



  • Issued in Japan and the U.S. as JP 6857875 (B2) and US 10,736,941 (B2).


  1. Yamaguchi, S. et al., Controlled Release (2017) 262, 232–238.
    [DOI] http://dx.doi.org/10.1016/j.jconrel.2017.07.037
  2. Ito, S. et al., Pharmaceutics (2021), 18, 1593–1603.
    [DOI] https://dx.doi.org/10.1021/acs.molpharmaceut.0c01010

Principal Investigator & Academic Institution

Shingo Ito, PhD (Associate Professor, Kumamoto University, Japan), et al.

Development Stages & Plans

  • Mixed oral insulin formulation with D-DNP peptide already developed.
  • Covalently bound oral insulin formulation with D-DNP peptide is under investigation.
  • In addition to insulin, the researchers can work on the development of various drugs using the D/L-DNP peptides.


TECH MANAGE is looking for a pharmaceutical company/start-up that is interested in licensing this invention for commercialization on behalf of Kumamoto University.  In addition to disclosing unpublished data, etc. by concluding a CDA with Kumamoto University, we can also arrange a meeting with the PI of this invention.
In addition to joint or budget-support research on this invention, we can also consider options such as exclusive evaluation for a certain period and preferential negotiation rights for the related patents’ licensing.
Please feel free to contact us with any requests you may have.





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