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 composition of peptide or protein drug and a compound having enhanced gastrointestinal enzymatic inhibition property to an intestinal tract of an animal subject, the method comprising delivering said composition that is loaded in an enteric-coated capsule to said animal subject orally, wherein said compound is a PGA-complexone conjugate and wherein said composition inside the capsule being delivered to said intestinal tract without contacting an acidic gastric fluid of said animal subject.
2. The method of claim 1 , wherein said capsule further comprises a pharmaceutically acceptable carrier, diluent, excipient, solubilizer, bubbling agent, or emulsifier.
3. The method of claim 1 , wherein said PGA-complexone conjugate is chelated to gadolinium.
4. The method of claim 1 , wherein said capsule further comprises at least one permeation enhancer.
5. The method of claim 4 , wherein said permeation enhancer is selected from the group consisting of Ca 2+ chatters, bile salts, surfactants, medium-chain fatty acids, phosphate esters, and chitosan.
6. The method of claim 5 , 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.
7. The method of claim 1 , wherein said drug is a pegylated drug.
8. The method of claim 1 , wherein said drug is covalently attached with polyethylene glycol polymer chains.
9. The method of claim 1 , wherein said drug is insulin, an insulin analog, or osteocalcin.
10. The method of claim 1 , wherein said drug is an insulin sensitizer.
11. The method of claim 1 , wherein said drug is an insulin secretagogue.
12. The method of claim 1 , wherein said drug is GLP-1 or a GLP-1 analog.
13. The method of claim 1 , wherein said drug is an inhibitor of dipeptidyl peptidase 4 (DIP-4 inhibitor).
14. The method of claim 1 , wherein said drug is excnatide, liraglutide, albiglutide, lixisenatide, or taspoglutide.
15. 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.
16. The method of claim 1 , wherein said PGA of the PGA-complexone conjugate is selected from the group consisting of γ-PGA, α-PGA, PGA derivatives, salts of PGA, and combinations thereof.
17. The method of claim 1 , wherein said drug is a monoclonal antibody.
18. The method of claim 1 , wherein said drug is a growth hormone.
19. The method of claim 1 , wherein said drug is an interferon, interleukin-11, or erythropoietin.
20. The method of claim 1 , wherein said drug is an anti-inflammatory drug, an anti-epileptic drug, an antibiotic, or an Alzheimer's antagonist.