Recombinant human growth hormone (rhGH) long-acting sustained-release microcapsule and preparation method thereof

Abstract

The invention relates to the field of medicine, and specifically, relates to a recombinant human growth hormone (rhGH) long-acting sustained-release microcapsule and a preparation method thereof. The preparation method of the rhGH long-acting sustained-release microcapsule comprises the following steps of 1, dissolving a diblock amphiphilic polymeric material in an organic solvent to obtain an oil phase O, 2, adding an rhGH-containing aqueous solution W1 or rhGH-containing particles S into the oil phase O obtained by the step 1, and carrying out emulsification preparation to obtain W1 / O or S / O primary emulsion, wherein the rhGH-containing aqueous solution W1 is utilized as an inner water phase, 3, adding the W1 / O or S / O primary emulsion into a stabilizer-containing outer water phase W2 to obtain W1 / O / W2 or S / O / W2 composite pre-emulsion, 4, carrying out a filter pressing process on the W1 / O / W2 or S / O / W2 composite pre-emulsion through a millipore membrane to obtain W1 / O / W2 or S / O / W2 composite emulsion, and 5, removing the organic solvent in the W1 / O / W2 or S / O / W2 composite pre-emulsion, carrying out solidification, centrifugal washing and freeze drying of the organic solvent-free W1 / O / W2 or S / O / W2 composite emulsion. The rhGH long-acting sustained-release microcapsule obtained by the preparation method has the advantages of even size, high encapsulation efficiency, high activity, low burst release quantity, good repeatability, simpleness of operation, and benefit to drug effect activity keeping and industrialized mass production.

Description

technical field [0001] The invention relates to the field of medicine, in particular to recombinant human growth hormone rhGH long-acting slow-release microcapsules and a preparation method thereof. Background technique [0002] Recombinant human growth hormone (rhGH) is widely used clinically to treat various diseases such as dwarfism, severe burns, and lipodystrophy in AIDS patients. The half-life in the body is short (0.5 hours), and there is an urgent need to develop rhGH long-acting sustained-release preparations . The traditional preparation method of rhGH microcapsules is mainly mechanical stirring or using a homogenizer. The particle size of the prepared microcapsules is very large, reaching tens or even hundreds of microns, and the size is uncontrollable. Inhomogeneous particle size leads to uneven distribution of drugs in small particle size microcapsules, which makes it difficult to improve the embedding rate, and will inevitably cause poor repeatability of prepa...

AI Technical Summary

Problems solved by technology

[0005] Chinese patent (publication number CN1187120) also discloses a method for preparing and using a sustained-release human growth hormone (hGH) composition, which solves the problem of providing subjects with sustained-release therapeutically effective blood level doses of hGH within one month, But need to use metal ion zinc Zn 2+ Stable growth hormone meets the requirements of sustained release, and the preparation process is complicated; in addition, due to the addition of Zn in the preparation process 2+ , which brings difficulties to the determination and removal of residues, which is not conducive to large-scale industrial production

This higher burst release causes the blood drug concentration to be too high, exceeding the effective use concentration, resulting in excessive drug concentration in the body causing or aggravating side effects; and causing drug waste, resulting in the sustained release of the drug that cannot reach the effective concentration in the later stage

In general, when preparing recombinant human growth hormone-loaded sustained-release microcapsules, the microcapsules prepared by the prior art have uneven particle size, poor reproducibility, and low bioavailability; protein drugs are prone to aggregates during the preparation and release process (more than 15% is obvious aggregation), resulting in immunogenicity and loss of activity; additional excipients are required to obtain a higher drug embedding rate and sustainable release, resulting in difficulties in the determination of residual residues in the later stage and reduced biological safety

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