Preparation method of bupivacaine multivesicular liposome

A multivesicular liposome and bupivacaine technology, which is applied in liposome delivery, medical preparations containing non-active ingredients, medical preparations containing active ingredients, etc., can solve the problem of agglomeration, phospholipid fragmentation, and floc formation problems such as substances, to achieve the effect of preventing aggregation, improving stability, and appropriate concentration

Active Publication Date: 2021-12-17
KINDOS PHARM CO LTD +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Improper process control in the liquid preparation process can easily cause phospholipids to break up, agglomerate, produce flocs, and float in the solution

Method used

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  • Preparation method of bupivacaine multivesicular liposome
  • Preparation method of bupivacaine multivesicular liposome
  • Preparation method of bupivacaine multivesicular liposome

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0030] A preparation method of bupivacaine multivesicular liposomes, comprising the following steps:

[0031] A. Preparation of three-phase solution

[0032] A phosphoric acid aqueous solution with a concentration of 15mg / mL is used as the inner water phase;

[0033] Mix bupivacaine, lipid components and dichloromethane to form an organic phase, and the concentration of bupivacaine is 35mg / mL;

[0034] Glucose, L-lysine and sodium chloride solution are mixed to form an external aqueous phase;

[0035] B, mixing the inner aqueous phase with the organic phase to form the first phase W / O;

[0036] C. Mix the first phase W / O with a certain volume of external water, and stir to form W / OW colostrum;

[0037] D. Mix the W / OW colostrum with a certain volume of external water again, stir to form a W / OW double emulsion, remove the organic solvent, and obtain multivesicular liposomes.

[0038] The L-lysine concentration in the external water phase is 3mg / mL, the glucose concentration...

Embodiment 2

[0041] A preparation method of bupivacaine multivesicular liposomes, comprising the following steps:

[0042] A. Preparation of three-phase solution

[0043] A phosphoric acid aqueous solution with a concentration of 30mg / mL is used as the inner water phase;

[0044] Mix bupivacaine, lipid components and dichloromethane to form an organic phase, and the concentration of bupivacaine is 45mg / mL;

[0045] Glucose, L-lysine and sodium chloride solution are mixed to form an external aqueous phase;

[0046] B. Mix the inner aqueous phase with the organic phase to form the first phase W / O;

[0047] C. Mix the first phase W / O with a certain volume of external water phase, and stir to form W / OW colostrum;

[0048] D. Mix the W / OW colostrum with a certain volume of external water again, stir to form a W / OW double emulsion, remove the organic solvent, and obtain multivesicular liposomes.

[0049] The concentration of L-lysine in the external aqueous phase is 2 mg / mL, the concentratio...

Embodiment 3

[0052] A preparation method of bupivacaine multivesicular liposomes, comprising the following steps:

[0053] A. Preparation of three-phase solution

[0054] Phosphoric acid aqueous solution with a concentration of 20mg / mL is used as the inner water phase;

[0055] Mix bupivacaine, lipid components and dichloromethane to form an organic phase, and the concentration of bupivacaine is 40mg / mL;

[0056] Glucose, L-lysine and sodium chloride solution are mixed to form an external aqueous phase;

[0057] B. Mix the inner aqueous phase with the organic phase to form the first phase W / O;

[0058]C. Mix the first phase W / O with a certain volume of external water phase, and stir to form W / OW colostrum;

[0059] D. Mix the W / OW colostrum with a certain volume of external water again, stir to form a W / OW double emulsion, remove the organic solvent, and obtain multivesicular liposomes.

[0060] Glucose is also contained in the inner aqueous phase.

[0061] The concentration of L-lysi...

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Abstract

The invention provides a preparation method of bupivacaine multivesicular liposome. The preparation method comprises the following steps: taking a phosphoric acid water solution with the concentration of 15 mg / mL to 30 mg / mL as an inner water phase; mixing bupivacaine, a lipid component and dichloromethane to form an organic phase, wherein the concentration of the bupivacaine is 35 mg / mL to 45 mg / mL; mixing glucose, L-lysine and a sodium chloride solution to form an outer water phase; mixing the inner water phase with the organic phase to form a first phase W / O; mixing the first phase W / O with the outer water phase with a certain volume; carrying out stirring to form W / OW primary emulsion; mixing the W / OW primary emulsion with the outer water phase with a certain volume again; carrying out stirring to form W / OW compound emulsion; and removing an organic solvent to obtain the stable multivesicular liposome. The method is a stable and reliable preparation method of the multivesicular liposome, which can be used for commercial production.

Description

technical field [0001] The invention belongs to the technical field of pharmaceutical equipment, and in particular relates to a preparation method of bupivacaine multivesicular liposomes. Background technique [0002] The multivesicular liposomes of bupivacaine have a non-concentric honeycomb shape, which is a nearly spherical preparation composed of multiple small chambers squeezed together. Because it can accumulate at the injection site, the small chambers gradually rupture to release the capsules wrapped in the inner cavity. Drugs, so as to achieve good sustained-release purposes, improve the drug-loading capacity of traditional liposome drugs, and prolong the drug release time. Multivesicular liposomes are prepared by mixing the drug-containing internal aqueous phase with the organic phase to prepare the first phase W / O, and then disperse the first phase W / O into the external aqueous phase to obtain a more stable dispersed W / OW emulsion , by rapidly removing the organi...

Claims

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Application Information

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Patent Type & AuthorityApplications(China)
IPC IPC(8): A61K9/127A61K31/445A61K47/02A61K47/18A61K47/26A61K9/113
CPCA61K31/445A61K9/1271A61K9/1277A61K47/183A61K47/02A61K9/113A61K47/26A61K9/0019
Inventor李娜史宣宇田欣欣
OwnerKINDOS PHARM CO LTD