Local anesthetic analgesic sustained-release drug delivery system, preparation method and application thereof

A method of preparing a local anesthetic analgesic sustained-release drug delivery system, comprising:

• (1) preparation of internal aqueous phase
• dissolving analgesic with a drug solvent and a drug solubilizer if the analgesic is in a free base form;
• and if the analgesic is in an acid saline form, replacing the acid radical contained in the analgesic with an acid radical containing N or P, and then dissolving the analgesic with a drug solvent and a drug solubilizer;
• (2) preparation of external aqueous phase
• dissolving substances selected from one or more of saccharide, ring-shaped organic acid, organic base and deflocculant with water to obtain an external aqueous phase, wherein the organic base is used to regulate the pH value of the external aqueous phase;
• (3) preparation of oil phase
• dissolving synthetic phosphatidylcholine, synthetic phosphatidylglycerol, cholesterol and glyceride with an organic solvent to obtain an oil phase;
• (4) preparation of primary emulsion
• adding the prepared internal aqueous phase into the oil phase in a volume ratio of 1:10-10:1 of the internal aqueous phase to the oil phase, and shearing at 10,000-16,000 rpm for 5-20 min to obtain a primary emulsion;
• (5) preparation of multiple emulsion
• adding the primary emulsion into the external aqueous phase in a volume ratio of 1:5-1:50 of the primary emulsion to the external aqueous phase, shearing at 1,000-4,000 rpm for 5-60 seconds;
• then adding the external aqueous phase which is 5-20 times the volume of the primary emulsion, blowing with 40-90 L/min of nitrogen at 20-40° C. for 5-30 min or performing rotary evaporation at 20-40° C.;
• removing the organic solvent, collecting an intermediate of multivesicular liposome, centrifuging the intermediate at 100-20,000 rpm for 10-30 min;
• discarding a supernatant, flushing a precipitate by an isoosmotic regulator, and regulating pH to 5.0-8.0 with a pH regulator to obtain the multivesicular liposome of from 1 μm to 50 μm in size.