Method of producing a microsphere comprising PLGA or PLA in which a biologically active substance is uniformly dispersed

Patent metadata

Field	Value
Publication number	US-12201728-B2
Application number	US-202217673429-A
Country	US
Kind code	B2
Filing date	Feb 16, 2022
Priority date	May 8, 2020
Publication date	Jan 21, 2025
Grant date	Jan 21, 2025

Abstract

The present application provides a microsphere comprising a lactic acid-glycolic acid copolymer (PLGA) or polylactide (PLA) as a main component, in which a biologically active substance is uniformly dispersed, wherein an average volume-based particle diameter of the microsphere is 1 μm or more and 150 μm or less, and a variation coefficient of area ratios in six regions is 0.35 or less, wherein the area ratios in six regions are calculated by (s/A)×100 (%) wherein the six regions are prepared by preparing a cross section observation sample obtained by cutting the microsphere; observing the cross section observation sample with an electron microscope at a magnification capable of confirming the biologically active substance in the microsphere or a higher magnification; and dividing the electron microscope observation image into six regions; and A is an area of a respective divided region, and s is a sum of cross section areas of the biologically active substance included in the respective divided region. The microsphere of the present invention can appropriately control the initial release amount of the biologically active substance and its release rate during a subsequent release period, and can continuously release the biologically active substance in vivo for a predetermined period of time.

First claim

The invention claimed is:

1. A method of producing a microsphere comprising a lactic acid-glycolic acid copolymer (PLGA) or polylactide (PLA) as a main component, in which a biologically active substance is uniformly dispersed, comprising:
a step of continuously feeding to a pulverizing apparatus a solution of the PLGA or PLA and the biologically active substance obtained by dissolving or dispersing the PLGA or PLA and the biologically active substance in a good solvent of PLGA or PLA, and a solution containing a poor solvent of PLGA or PLA to prepare emulsified particles; and removing the good solvent from the prepared emulsified particles to precipitate the microsphere;
wherein the good solvent is a solvent which dissolves 0.1 g or more of PLGA or PLA in 100 g of the solvent at 25° C., and the poor solvent is a solvent which dissolves only 0.05 g or less of PLGA or PLA in 100 g of the solvent at 25° C.,
an average volume-based particle diameter of the microsphere is 1 μm or more and 150 μm or less, and
a variation coefficient of area ratios of an area of the biologically active substance to a cross-section area of the microsphere in six regions of the microsphere is 0.35 or less.

2. The method according to claim 1 , wherein the biologically active substance is a lipophilic biologically active substance.

3. The method according to claim 1 , wherein an average volume-based particle diameter of the dispersed biologically active substance is 5 nm to 500 nm.

4. The method according to claim 1 , wherein a content of the biologically active substance in the microsphere is 0.35 to 1.5% by mass.

5. The method according to claim 1 , wherein the good solvent is removed by blowing a gas on a surface of a fluid containing the emulsified particles, while stirring the fluid.

Assignees

• M Technique Co Ltd

Inventors

• Enomura Masakazu
• Araki Kaeko

Classifications

• A61K9/1647 Primary

  Polyesters, e.g. poly(lactide-co-glycolide) · CPC title

• A61K31/57

  substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone · CPC title

• A61K31/10

  Sulfides; Sulfoxides; Sulfones · CPC title

• A61K9/0024

  Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue (compositions for intravenous administration, normal injectable solutions or dispersions for, e.g. subcutaneous administration A61K9/0019; brain implants A61K9/0085; (coated) prostheses, catheters or stents A61L) · CPC title

• A61K9/1641

  obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poloxamers · CPC title