Pharmaceutical composition of peptide drug and enzyme-inhibition compounds
View Patent ↗The invention relates to a method of co-administering a peptide or protein drug with an enzyme-resistant PGA-complexone compound orally so to mitigate enzyme attack in the gastrointestinal tract of an animal subject.
1. A method of delivering a drug with enhanced enzymatic inhibition property to an animal subject, the method comprising co-administering a PGA-complexone conjugate and a composition of nanoparticles that are loaded with said drug to said animal subject orally, wherein the nanoparticles consist of positively charged chitosan, a negatively charged substrate, optionally a zero-charge compound, and said drug.
2. The method of claim 1 , wherein the PGA-complexone conjugate is PGA-DTPA.
3. The method of claim 1 , wherein said PGA-complexone conjugate and said nanoparticles are formulated into a tablet or pill configuration.
4. The method of claim 3 , wherein said tablet or pill is treated with an enteric coating polymer.
5. The method of claim 1 , wherein said PGA-complexone conjugate and said nanoparticles are encapsulated in a capsule.
6. The method of claim 5 , wherein said capsule further comprises a pharmaceutically acceptable carrier, diluent, or excipient, a solubilizer, bubbling agent, or emulsifier.
7. The method of claim 5 , wherein said capsule is treated with an enteric coating polymer.
8. The method of claim 5 , wherein said capsule further comprises at least one permeation enhancer.
9. The method of claim 8 , wherein said permeation enhancer is selected from the group consisting of Ca 2+ chelators, bile salts, surfactants, medium-chain fatty acids, phosphate esters, and chitosan.
10. The method of claim 9 , wherein said chitosan is selected from the group consisting of N-trimethyl chitosan (TMC), low MW-chitosan, EDTA-chitosan, pegylated chitosan (PEG-chitosan), mono-N-carboxymethyl chitosan (MCC), chitosan derivatives, and combinations thereof.
11. The method of claim 1 , wherein said drug is a pegylated drug.
12. The method of claim 1 , wherein said drug is covalently attached with polyethylene glycol polymer chains.
13. The method of claim 1 , wherein said drug is insulin, an insulin analog, or osteocalcin.
14. The method of claim 1 , wherein said drug is an insulin sensitizer.
15. The method of claim 1 , wherein said drug is an insulin secretagogue.
16. The method of claim 1 , wherein said drug is GLP-1 or a GLP-1 analog.
17. The method of claim 1 , wherein said drug is an inhibitor of dipeptidyl peptidase 4 (DIP-4 inhibitor).
18. The method of claim 1 , wherein said drug is exenatide, liraglutide, albiglutide, lixisenatide, or taspoglutide.
19. The method of claim 1 , wherein said drug is selected from the group consisting of alpha-glucosidase inhibitors, amylin analog, sodium-glucose co-transporter type 2 (SGLT2) inhibitors, benfluorex, and tolrestat.
20. The method of claim 1 , wherein said chitosan is selected from the group consisting of N-trimethyl chitosan (TMC), low MW-chitosan, EDTA-chitosan, pegylated chitosan (PEG-chitosan), mono-N-carboxymethyl chitosan (MCC), chitosan derivatives, and combinations thereof.