Apelin liposome and preparation method thereof

Abstract

The invention provides an Apelin liposome and a preparation method thereof. The Apelin liposome comprises Apelin, phosphatidylglycerol, phosphatidylcholine, cholesterol, phosphatidyl ethanolamine-polyethylene glycol derivatives, and the molar ratio of Apelin to phosphatidylglycerol is (1:2)-(1:10). The Apelin liposome achieves highly efficient encapsulation of Apelin, the encapsulation efficiencyis more than 90%, and meanwhile the half-life period of Apelin in vivo is significantly prolonged.

Description

technical field [0001] The invention belongs to the field of pharmaceutical preparations, and in particular relates to an Apelin liposome and a preparation method thereof. Background technique [0002] Apelin is an important functional peptide in the human body. Under the action of protease in vivo, the Apelin propeptide containing 77 amino acids is cleaved into active Apelin fragments, which can be divided into Apelin-13 (thirteen peptides) and pyroglutamic acid-type Apelin-13 ( [Pyrl]-Apelin-13), Apelin-17 (17-peptide), Apelin-36 (36-peptide), Apelin-55 (55-pentadepeptide), etc. (European Journal of Pharmacology2015, 763: 149-159) , herein, the above-mentioned Apelin fragments are collectively referred to as "Apelin". [0003] Apelin is the endogenous ligand of the angiotensin II-like-1 receptor (APJ). APJ receptor, also known as Apelin receptor, is a member of the orphan G-protein-coupled receptor (GPCR) family. The structure of the APJ receptor is similar to the angi...

AI Technical Summary

Problems solved by technology

However, the preparation process of this liposome is a film dispersion method, which belongs to the laboratory stage technology, and it is difficult to realize industrialized large-scale production.

The disadvantage is that the liposome disclosed in this patent only has an encapsulation efficiency of about 30% for Apelin, and has not realized its efficient encapsulation

In addition, dichloromethane or chloroform is used in this process, which is likely to cause greater toxicity to the central nervous system of the organism, and even induce serious side effects such as teratogenicity and mutagenesis. Therefore, it is necessary to strictly control solvent residues and indirectly increase cost of production

[0007] In summary, it is not difficult to find that although the existing chemical modification and physical encapsulation technologies can prolong the half-life of Apelin in vivo or the in vivo action time to a certain extent, there are still certain problems, such as the chemical modification of Apelin to a certain extent. It reduces the original activity of the drug, difficulty in industrialization, and low yield; while the preparation process of the liposome technology disclosed in US2016 / 0058705 A1 is a thin film dispersion method, which belongs to the laboratory stage technology, and there are also difficulties in industrialization and other problems, the disadvantage is that the encapsulation rate of Apelin by this process is low, which does not meet the actual clinical drug needs

In addition, organic solvents such as dichloromethane or chloroform used in this process are likely to cause harm to the human body and the environment

Although organic solvents such as dichloromethane or chloroform can be removed in the terminal preparation by some technical means, it also increases the risk of clinical drug use of liposomes through human intravenous injection

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