Process for producing a lactic acid-glycolic acid copolymer or a salt thereof

Patent metadata

Field	Value
Publication number	US-10011681-B2
Application number	US-201414782145-A
Country	US
Kind code	B2
Filing date	Apr 8, 2014
Priority date	Apr 11, 2013
Publication date	Jul 3, 2018
Grant date	Jul 3, 2018

Abstract

Provided is a purified lactic acid-glycolic acid copolymer, preferably in the form of powder, having a reduced content of dimers such as residual lactide and glycolide that can be produced by a simple industrial process without the use of any high-shear special device. Further provided is a high-purity lactic acid-glycolic acid copolymer which has small amounts of dimers such as residual lactide and glycolide and small amounts of a low-molecular weight lactic acid-glycolic acid copolymer or a salt thereof and which has a small ratio of weight average molecular weight to number average molecular weight (Mw/Mn). The copolymer can be produced in accordance with a defined process.

First claim

The invention claimed is:

1. A process for producing a purified lactic acid-glycolic acid copolymer (A2) or a salt thereof comprising the steps of:
(1-1) dissolving a lactic acid-glycolic acid copolymer (A1) containing lactic acid units and glycolic acid units or a salt thereof into at least one organic solvent (B1) having a solubility at 25° C. of not less than 1 wt % to prepare a solution of the lactic acid-glycolic acid copolymer (A1) or the salt thereof;
(1-2) adding at least one solvent (S1) selected from water and aliphatic alcohols (B2) to the solution of the lactic acid-glycolic acid copolymer (A1) or the salt thereof to prepare a second solution including the lactic acid-glycolic acid copolymer (A1) or the salt thereof, the organic solvent (B1) and the at least one solvent (S1);
(2) adding the second solution prepared in the step (1-2) to a solvent (S2′) including at least one selected from water and aliphatic alcohols (B2) to precipitate a purified lactic acid-glycolic acid copolymer (A2) or a salt thereof; and
(3) recovering the precipitate of the purified lactic acid-glycolic acid copolymer (A2) or the salt thereof.

2. The process for producing a purified lactic acid-glycolic acid copolymer (A2) or a salt thereof according to claim 1 , wherein the lactic acid-glycolic acid copolymer (A1) contains 40 to 90 mol % of the lactic acid units and 60 to 10 mol % of the glycolic acid units (wherein the total of the lactic acid units and the glycolic acid units is 100 mol %).

3. The process for producing a purified lactic acid-glycolic acid copolymer (A2) or a salt thereof according to claim 1 , wherein the lactic acid-glycolic acid copolymer (A1) has a weight average molecular weight (Mw) in the range of 4,500 to 110,000.

4. The process for producing a purified lactic acid-glycolic acid copolymer (A2) or a salt thereof according to claim 1 , wherein in the step (1-1), the lactic acid-glycolic acid copolymer (A1) or the salt thereof is dissolved into the organic solvent (B1) with a concentration of 1 to 50 wt %.

5. The process for producing a purified lactic acid-glycolic acid copolymer (A2) or a salt thereof according to claim 1 , wherein the organic solvent (B1) used in the step (1-1) is an aprotic polar organic solvent.

6. The process for producing a purified lactic acid-glycolic acid copolymer (A2) or a salt thereof according to claim 1 , wherein the addition in the step (2) is dropwise addition.

7. The process for producing a purified lactic acid-glycolic acid copolymer (A2) or a salt thereof according to claim 1 , wherein in the step (2), the purified lactic acid-glycolic acid copolymer (A2) or the salt thereof is precipitated as a powder.

8. The process for producing a purified lactic acid-glycolic acid copolymer (A2) or a salt thereof according to claim 1 , wherein the process comprises the steps of:
(1-1) dissolving a lactic acid-glycolic acid copolymer (A1) or a salt thereof into at least one organic solvent (B1) having a solubility at 25° C. of not less than 1 wt % to prepare a 1-50 wt % solution of the lactic acid-glycolic acid copolymer (A1) or the salt thereof, the lactic acid-glycolic acid copolymer (A1) containing 40 to 90 mol % of lactic acid units and 60 to 10 mol % of glycolic acid units (wherein the total of the lactic acid units and the glycolic acid units is 100 mol %) and having a weight average molecular weight (Mw) in the range of 4,500 to 110,000;
(1-2-A) adding at least one solvent (S1) selected from water and aliphatic alcohols (B2) to the solution of the lactic acid-glycolic acid copolymer (A1) or the salt thereof to prepare a second solution including the lactic acid-glycolic acid copolymer (A1) or the salt thereof, the organic solvent (B1) and the at least one solvent (S1);
(2) adding dropwise the second solution prepared in the step (1-2-A) to at least one solvent (S2) selected from water and aliphatic alcohols (B2) to precipitate a purified lactic acid-glycolic acid copolymer (A2) or a salt thereof as a powder; and
(3) recovering the precipitate of the purified lactic acid-glycolic acid copolymer (A2) or the salt thereof.

9. The process for producing a purified lactic acid-glycolic acid copolymer (A2) or a salt thereof according to claim 1 , wherein the amount of the solvent (S1) used in the step (1-2) is 0.05 to 2.5 times by weight the amount of the organic solvent (B1).

10. The process for producing a purified lactic acid-glycolic acid copolymer (A2) or a salt thereof according to claim 1 , wherein the temperature of the solvent (S2′) used in the step (2) is from the solidification point of the solvent (S2′) to 25° C.

11. The process for producing a purified lactic acid-glycolic acid copolymer (A2) or a salt thereof according to claim 1 , wherein the amount of the solvent (S2′) used in the step (2) is 3 or more times by weight the amount of the organic solvent (B1).

12. A process for producing a purified lactic acid-glycolic acid copolymer (A2) or a salt thereof comprising the steps of:
(1-1) dissolving a lactic acid-glycolic acid copolymer (A1) containing lactic acid units and glycolic acid units or a salt thereof into at least one organic solvent (B1) having a solubility at 25° C. of not less than 1 wt % to prepare a solution of the lactic acid-glycolic acid copolymer (A1) or the salt thereof;
(1-2-B1) adding at least one solvent (B2) selected from water and aliphatic alcohols to the solution of the lactic acid-glycolic acid copolymer (A1) or the salt thereof and stirring the mixture to separate the mixture into two liquid phases; and
(1-2-B2) recovering one of the two phases which includes the lactic acid-glycolic acid copolymer or the salt thereof having a larger weight average molecular weight (Mw)
(2) adding the phase recovered in the step (1-2-B2) to a solvent including at least one selected from water and aliphatic alcohols to precipitate a purified lactic acid-glycolic acid (A2) or a salt thereof; and
(3) recovering the precipitate of the purified lactic acid-glycolic acid copolymer (A2) or the salt thereof.

13. The process for producing a purified lactic acid-glycolic acid copolymer (A2) or a salt thereof according to claim 12 , wherein the process comprises the steps of:
(1-1) dissolving a lactic acid-glycolic acid copolymer (A1) or a salt thereof into at least one organic solvent (B1) having a solubility at 25° C. of not less than 10 wt % to prepare a 10-50 wt % solution of the lactic acid-glycolic acid copolymer (A1) or the salt thereof, the lactic acid-glycolic acid copolymer (A1) containing 40 to 90 mol % of lactic acid units and 60 to 10 mol % of glycolic acid units (wherein the total of the lactic acid units and the glycolic acid units is 100 mol %) and having a weight average molecular weight (Mw) in the range of 4,500 to 105,000;
(1-2-B1) adding at least one aliphatic alcohol (B2) to the solution of the lactic acid-glycolic acid copolymer (A1) or the salt thereof and stirring the mixture to separate the mixture into two liquid phases;
(1-2-B2) recovering one of the two phases which includes the lactic acid-glycolic acid copolymer or the salt thereof having a larger weight average molecular weight (Mw);
(2) adding dropwise the phase recovered in the step (1-2-B2) to a solvent including water to precipitate a purified lactic acid-glycolic acid (A2) or a salt thereof; and
(3) recovering the precipitate of the purified lactic acid-glycolic acid copolymer (A2) or the salt thereof.

14. The process for producing a purified lactic acid-glycolic acid copolymer (A2) or a salt thereof according to claim 13 , wherein the solvent to which the recovered phase is added dropwise in the ste

Assignees

• Mitsui Chemicals Inc

Inventors

• Nagahara Kiyoteru
• Fukuiri Yasushi
• Kawabata Tomoyuki

Classifications

• A61K47/34

  Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers (A61K47/10 takes precedence) · CPC title

• C08G63/90 Primary

  Purification; Drying · CPC title

• C08G63/06

  derived from hydroxycarboxylic acids · CPC title