# US 5,705,197 A · Extraction process for producing PLGA microspheres

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 5,705,197 A
- Document ID: US5705197A
- Status: Granted
- Kind: A
- Application number: 08/698,896
- Filed: 1996-08-16
- Granted: 1998-01-06
- Earliest claimed: 1994-05-16
- Assignees: The United States of America as represented by the Secretary of the Army
- Inventors: John Van Hamont; Curt Thies; Robert H. Reid; Charles E. McQueen; Jean A. Setterstrom
- Web page: https://patentgrep.com/patent/US5705197A

## CPC

- A61K 39/39: characterised by the immunostimulating additives, e.g. chemical adjuvants
- A61K 9/1647: {Polyesters, e.g. poly(lactide-co-glycolide)}
- A61K 9/5031: {obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poly(lactide-co-glycolide)}
- A61K 38/00: Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00)
- A61K 2039/55555: {Liposomes; Vesicles, e.g. nanoparticles; Spheres, e.g. nanospheres; Polymers}
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)

## Abstract

A hybrid evaporation-extraction process for preparing microspheres of a p(DL-lactide-to-glycolide) biodegradable polymer, comprising: a. preparing a lyophilized biologically active material-sucrose matrix; adding acetonitrile solvent to biologically active material-sucrose matrix to form a solution; b. preparing a solution of a biodegradable poly (DL-lactide-co-glycolide) polymer by adding acetonitrile solvent to the polymer; c. adding the biodegradable poly (DL-lactide-co-glycolide) polymer acetonitrile solution to the biologically active material-sucrose acetonitrile solution; d. adding with stirring an oil containing lecithin to the poly (DL-lactide-co-glycolide) polymer-sucrose-biologically active material solution to evaporate acetonitrile and form an emulsion containing microspheres of poly (DL-lactide-co-glycolide) biodegradable polymers; e. adding the emulsion from step d. into a solvent selected from heptane, hexane, pentane or isopropanol; and f. collecting microspheres of poly (DL-lactide-co-glycolide) biodegradable polymers of from 1.0 to about 10.0 micrometers after filtration and washing with a fresh solvent selected from heptane, hexane, pentane or isopropanol.

## Claims

### Claim 1

A hybrid evaporation-extraction process for preparing microspheres of a poly(DL-lactide-to-glycolide) biodegradable polymer, comprising:
a. preparing a lyophilized biologically active material-sucrose matrix; adding acetonitrile solvent to biologically active material-sucrose matrix to form a solution;
b. preparing a solution of a biodegradable poly (DL-lactide-co-glycolide) polymer by adding acetonitrile solvent to the polymer;
c. adding the biodegradable poly (DL-lactide-co-glycolide) polymer acetonitrile solution to the biologically active material-sucrose acetonitrile solution;
d. adding with stirring an oil containing lecithin to the poly (DL-lactide-co-glycolide) polymer-sucrose-biologically active material solution to evaporate acetonitrile and form an emulsion containing microspheres of poly (DL-lactide-co-glycolide) biodegradable polymers;
e. adding the emulsion from step d. into a solvent selected from heptane, hexane, pentane or isopropanol; and
f. collecting microspheres of poly (DL-lactide-co-glycolide) biodegradable polymers of from 1.0 to about 10.0 micrometers after filtration and washing with a fresh solvent selected from heptane, hexane, pentane or isopropanol.

### Claim 2 (depends on 1)

The process of claim 1, wherein the oil is selected from machine oils of 5W30, 10W30, 10W40 and 15W50.

### Claim 3 (depends on 1)

The process of claim 1, wherein the oil is mineral oil.

### Claim 4 (depends on 1)

The process of claim 1, wherein the oil is a silcone oil.

### Claim 5 (depends on 1)

The process of claim 1, wherein relative ratios between the lactide and glycolide are 50:50.

### Claim 6 (depends on 1)

The process of claim 1, wherein said biologically active material is an antigen.

### Claim 7 (depends on 3)

The process of claim 3, wherein said mineral oil is at a temperature from about 20.degree. C. to about 40.degree. C.

### Claim 8 (depends on 7)

The process of claim 7, wherein lecithin is present in amounts of from about 0.1 to about 0.35% w/v of mineral oil.

### Claim 9 (depends on 8)

The process of claim 8, wherein evaporation of acetonitrile is at a temperature less than 30.degree. C.

### Claim 10 (depends on 9)

The process of claim 9, wherein said stirring in step d. is about 500 rpm.