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Microparticles with adsorbent surfaces, methods of making same, and uses thereof

a technology of adsorption surface and microparticle, which is applied in the field of pharmaceutical compositions, can solve the problems of difficult or impossible to adsorb charged or bulky biologically active agents, and can be problematic in adsorption of biologically active agents to the surface of microparticles, and achieve the effect of stimulating an immune respons

Inactive Publication Date: 2005-09-01
NOVARTIS VACCINES & DIAGNOSTICS INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

"The present invention is about a method of making microparticles with adsorbent surfaces that can adsorb a wide variety of macromolecules, such as pharmaceuticals, polynucleotides, polypeptides, hormones, enzymes, transcription or translation mediators, immunomodulators, antigens, and adjuvants. These microparticles are made by combining a polymer solution with a detergent, and then dispersing it in an organic solvent. The resulting microparticles have improved adsorbent surfaces compared to other methods, and can provide superior immune responses. The invention also includes methods of using these microparticles to deliver macromolecules to a vertebrate subject."

Problems solved by technology

While antigen-adsorbed PLG microparticles offer significant advantages over other more toxic systems, adsorption of biologically active agents to the microparticle surface can be problematic.
For example, it is often difficult or impossible to adsorb charged or bulky biologically active agents, such as polynucleotides, large polypeptides, and the like, to the microparticle surface.

Method used

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Examples

Experimental program
Comparison scheme
Effect test

example 1

Preparation of Blank Microparticles Using PVA as an Emulsion Stabilizer

[0101] Blank microparticles (e.g., without adsorbed or entrapped macromolecules) were made using polyvinyl alcohol (PVA) as follows. Solutions used: [0102] (1) 6% RG 504 PLG (Boehringer Ingelheim) in dichloromethane. [0103] (2) 10% polyvinyl alcohol (PVA) (ICN) in water.

[0104] In particular, the microparticles were made by combining 10 ml of polymer solution with 1.0 ml of distilled water and homogenizing for 3 minutes using an Omni benchtop homogenizer with a 10 mm probe at 10K rpm to form a water / oil (w / o) emulsion. The w / o emulsion was added to 40 ml of the 10% PVA solution, and homogenized for 3 minutes, to form a water / oil / water (w / o / w) emulsion. The w / o / w emulsion was left stirring overnight for solvent evaporation, forming microparticles. The formed microparticles were washed with water by centrifugation 4 times, and lyophilized. The microparticles were then sized in a Malvern Master sizer for future use...

example 2

Preparation of Blank Microparticles Using CTAB

[0105] Blank microparticles were produced using CTAB as follows. Solutions used: [0106] (1) 4% RG 504 PLG (Boehringer Ingelheim) in dimethyl chloride. [0107] (2) 0.5% CTAB (Sigma Chemical Co., St. Louis, Mo.) in water.

[0108] In particular, the microparticles were made by combining 12.5 ml of polymer solution with 1.25 ml of distilled water and homogenizing for 3 minutes using an Omni benchtop homogenizer with a 10 mm probe at 10K rpm to form a w / o emulsion. The w / o emulsion was added to 50 ml of the 0.5% CTAB solution and homogenized for 3 minutes to form a w / o / w emulsion. The w / o / w emulsion was left stirring overnight for solvent evaporation, forming microparticles. The formed microparticles were then filtered through a 38μ mesh, washed with water by centrifugation 4 times, and lyophilized. The microparticles were then sized in a Malvern Master sizer for future use.

example 3

Preparation of Blank Microparticles Using SDS

[0109] Blank microparticles were produced using SDS as follows. Solutions used: [0110] (1) 6% RG 504 PLG (Boehringer Ingelheim) in dimethyl chloride. [0111] (2) 1% SDS (Sigma Chemical Co., St. Louis, Mo.) in water.

[0112] In particular, the microparticles were made by combining 12.5 ml of polymer solution with 50 ml of the SDS solution and homogenizing for 3 minutes using an Omni benchtop homogenizer with a 10 mm probe at 10K rpm. The emulsion was left stirring overnight for solvent evaporation. The formed microparticles were filtered through a 38μmesh, washed with water by centrifugation 4 times, and lyophilized for future use. The microparticles were then sized in a Malvern Master sizer for future use.

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Abstract

Microparticles with adsorbent surfaces, methods of making such microparticles, and uses thereof, are disclosed. The microparticles comprise a polymer, such as a poly(α-hydroxy acid), a polyhydroxy butyric acid, a polycaprolactone, a polyorthoester, a polyanhydride, and the like, and are formed using cationic, anionic, or nonionic detergents. The surface of the microparticles efficiently adsorb biologically active macromolecules, such as DNA, polypeptides, antigens, and adjuvants.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS [0001] This application is a continuation of U.S. patent application Ser. No. 09 / 581,772, filed Jun. 15, 2000, which is a 371 of International Application No. PCT / US99 / 17308, filed Jul. 29, 1999, which is a continuation-in-part of U.S. patent application Ser. No. 09 / 285,855, filed Apr. 2, 1999, which is a continuation-in-part of U.S. patent application Ser. No. 09 / 124,533, filed Jul. 29, 1998, which is a continuation-in-part of U.S. patent application Ser. No. 09 / 015,652, filed Jan. 29, 1998, which claims the benefit of U.S. Provisional Application Ser. Nos. 60 / 036,316, filed Jan. 30, 1997 and 60 / 069,749, filed Dec. 16, 1997. Each of the above applications are incorporated herein by reference in their entireties.TECHNICAL FIELD [0002] The present invention relates generally to pharmaceutical compositions. In particular, the invention relates to microparticles with adsorbent surfaces, methods for preparing such microparticles, and uses thereof....

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K9/00A61K9/16A61K39/12A61K39/145A61K39/21A61K39/245A61K39/39
CPCA61K9/1647A61K2039/545A61K39/12A61K39/21A61K39/245A61K39/39A61K2039/55555C12N2740/16111C12N2770/24211C12N2770/24234A61K2039/53A61K2039/543A61K2039/55505A61K2039/55561C12N2740/16134C12N2740/16234A61K9/167
Inventor O' HAGAN, DEREKSINGH, MANMOHANOTT, GARYBARACKMAN, JOHNKAZZAZ, JINA
Owner NOVARTIS VACCINES & DIAGNOSTICS INC