Oral PEGylated insulin pH-sensitive naonparticle and preparation method thereof

Abstract

The invention discloses an oral PEGylated insulin pH-sensitive naonparticle and a preparation method thereof. The naonparticle is prepared from PEGylated insulin, pH-sensitive polymer, carrier, additives and stabilizer. The preparation method of the naonparticle comprises the following steps: preparing a PEGylated insulin / pH-sensitive polymer / carrier W / O primary emulsion, dispersing the W / O primary emulsion in a stabilizer solution to form a W / O / W multiple emulsion, obtaining a crude product after the solvent volatilizes, purifying the crude product, and carrying out freeze-drying to obtain the naonparticle. The PEGylated insulin pH-sensitive naonparticle disclosed by the invention has the advantages of uniform dispersion and high medicine enveloping rate; the insulin modified by polyethylene glycol can reduce the aggregation of insulin molecules, prolong the half life in vivo, and prolong the time of blood sugar reduction effect; and the release rate of the insulin in the gastric acid environment is reduced, the release rate of the insulin in the intestinal tract environment is enhanced since the naonparticle swells, and thus, the oral PEGylated insulin pH-sensitive naonparticle has an oral application value.

Description

technical field [0001] The invention belongs to the field of biomedicine and relates to a pH-sensitive nanoparticle and a preparation method thereof, in particular to an oral pegylated insulin pH-sensitive nanoparticle and a preparation method thereof. Background technique [0002] Common routes of drug administration include: oral, intravenous, intramuscular, and subcutaneous injections. Compared with other methods of administration, oral administration has the advantages of convenience, safety, relatively low cost, and good patient compliance. However, the route of oral administration has many limitations, and many factors in the administration process will affect the absorption of oral drugs. Most peptide and protein drugs are difficult to pass through the biomembrane barrier due to their large molecular weight and poor fat solubility. Moreover, due to the presence of a large number of peptidases and proteolytic enzymes in the gastrointestinal tract, they are easily elim...

AI Technical Summary

Problems solved by technology

Disclosed a kind of PLGA preparation containing pegylated insulin in U.S. Patent No.09 / 999,82 as Lewis et al., this preparation can reduce blood sugar concentration in the animal body through subcutaneous injection, but can not be directly used for oral administration, and it comprises The sealing rate is only 33~49.2%; while Hinds et al [Kenneth Hinds, Kathleen Campbell, Kathleen Holland, PEGylated insulin in PLGA microparticles. In vivo and in vitro analysis, J Control Release, 2005, 104: 447-460] adopt the single emulsion method Using PLGA to encapsulate PEGylated insulin, the prepared microparticles have a higher drug loading capacity, but they are also not pH sensitive and can only be used for injection preparations

Existing pH-sensitive PEGylated insulin also has many deficiencies, such as [P. Calceti, S. Salmaso, G. Walker, A. Bernkop-Schnürch, Development and in vivo evaluation of an oral insulin–PEG delivery by Calceti et al. system, Eur J Pharm Sci, 2004, 22: 315] preparation of pegylated insulin tablets for improving the stability and oral bioavailability of pegylated insulin, the pegylated insulin tablets are adhered by membrane Composed of non-toxic polyacrylic acid-cysteine, the surface layer of the tablet is L100-55 enteric coating, the tablet shows pH-sensitive release characteristics, but the ability of the drug to be absorbed is poor, and it is not as good as nanoparticles, which is more conducive to the absorption of biomacromolecules absorb

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