Advantages
- Oral drug: Only consists of a mixture of the peptide invention and the insulin hexamer used in existing injectable formulations.
- Efficacy confirmed: In vivo experimental data available.
Technology Overview & Background
Insulin is widely used as a treatment for diabetes. However, the patient’s quality of life (QOL) is low because of the need for pre-meal injections at each meal and the need for a daily injection for basal insulin supplementation. Thus, the development of a less invasive administration method is strongly desired. On the other hand, the background to the difficulties in developing oral drugs is their breakdown by digestive enzymes and the difficulty of absorption in the small intestine. Among these problems, enteric soluble formulation technology has been developed to prevent inactivation by digestive enzymes in the stomach, and drugs can now be delivered to the intestinal tract, but the issue of improving absorption efficiency in the small intestine is still far from satisfactory.
The researchers have previously identified cyclic peptides with high small intestinal permeability, which is named DNP peptides. As a result of further research, they have developed D-DNP peptides consisting of D-amino acids, which are not easily degraded in vivo. They have experimentally confirmed that an oral insulin preparation with high small intestinal absorption can be obtained simply by partially modifying this D-DNP peptide and mixing it with insulin, which is used in existing drugs.
Data
- An insulin-binding peptide was linked to the C-terminal of the D-DNP peptide and administered orally to mice in a mixture with insulin. The results showed that insulin reached the small intestine without being degraded and further penetrated the intestinal tract to increase the concentration of insulin in portal plasma, resulting in a significant decrease in blood glucose levels (unpublished data).
- When insulin was changed from a monomer to a hexamer stabilized with zinc ions (Zn-insulin; used in existing injectable formulations), it was found to be more resistant to degradation in the small intestine, further promoting insulin absorption in mice and lowering blood glucose levels.
Publications
- Yamaguchi, S. et al., Controlled Release (2017) 262, 232–238.
[DOI] http://dx.doi.org/10.1016/j.jconrel.2017.07.037 - Ito, S. et al., Pharmaceutics (2021), 18, 1593–1603.
[DOI] https://dx.doi.org/10.1021/acs.molpharmaceut.0c01010
Patents
PCT/JP2016/064767; issued in Japan and U.S. as JP 6857875 (B2) and US 10,736,941 (B2).
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 this D/L-DNP peptides.
Expectations
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.
Project No. JT-04676(a)