Device for continuously producing exenatide microspheres and method for controlling release rate of microspheres

Abstract

The invention discloses a device for continuously producing exenatide microspheres and a method for controlling the release rate of microspheres. By adopting the device disclosed by the invention, a high pressure gas in a high pressure container is transferred to a squeezing device through a pipe, microspheres are squeezed, are solidified in a primary solidification device and then enter a soft microsphere collector, a hydraulic transfer valve is used to transfer the microspheres to a large-volume device, the microspheres are stirred and solidified, the microspheres are collected to perform freeze drying for standby. The method disclosed by the invention comprises the following steps: dissolving drug powder in a strongly polar solvent B1, then adding the solution in a weakly polar solvent B2 dissolved with a polymer according to a ratio, wherein the drug can not be dissolved in the solvent B2 and the solvent B1 and the solvent B2 are completely mutually soluble; adding a water-soluble substance C in the B1 / B2 mixed solvent, performing high-speed stirring to mix the solution evenly, then dispersing the prepared suspension in the aqueous phase, and volatilizing the organic solvent to obtain the controlled release microspheres encapsulating the drug. Compared with the prior art, the exenatide poly(lactic-co-glycolic acid) (PLGA) controlled release microspheres which has high encapsulation rate, no burst effect and can be released evenly and completely, are successfully prepared by the method disclosed by the invention.

Description

technical field [0001] The invention relates to a method for efficiently encapsulating exenatide into PLGA polymers, and adjusting the microspheres to achieve uniform and complete release by adding alkaline substances of different concentrations, and a method for controlling the uniformity of exenatide microspheres installation. Background technique [0002] Sustained and controlled release microspheres are an important sustained and controlled release drug delivery system (Drug Delivery System DDS). By encapsulating the active ingredient in the polymer, the active ingredient can be released from the microspheres in a long-term, stable and controllable manner, so as to achieve the purpose of slow release and controlled release. In particular, there are very few slow- and controlled-release microspheres for proteins or polypeptides. With the continuous improvement of medical care, protein and polypeptide drugs will inevitably become the mainstream of future drugs, but slow- ...

AI Technical Summary

Problems solved by technology

When using physical methods to reduce the particle size of polypeptides and protein particles, it often causes changes in the structure of polypeptides and proteins, resulting in the inactivation and deformation of proteins and polypeptides, thereby reducing the drug efficacy; at the same time, in the production process, physical methods Reducing the particle size will use a lot of mechanical energy, resulting in a significant increase in cost

[0009] Some researchers have improved the preparation of microspheres by the S / O / W double emulsification method, by pre-dissolving the polypeptide in a strong polar solvent, and then adding this solvent to a weak polar solvent in which the polymer is dissolved. Using the anti-solvent effect, the peptide is precipitated in a weak polar solvent to form a suspension with uniformly dispersed fine particles, so that microspheres are further prepared by S / O / W (patent 200410053612.3, Shanghai Huayi Biotechnology Co., Ltd.). It is more advantageous to reduce the particle size of polypeptide and protein particles by physical methods, but the microspheres prepared by it still have severe burst release and incomplete release.

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