Improved preparation of molecular imprinted polymers

A technology of molecular imprinting and polymers, which is applied in the field of pharmaceutical preparations that bind target molecules such as cholesterol, bile acids and bile salts, and can solve the problems of undisclosed separation of inefficient or non-conjugates, undisclosed, etc.

Active Publication Date: 2009-04-29
MIPSALUS APS
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

Moreover, US 5,994,110 does not disclose any method for isolating "good binders" of suspended insoluble MIP on...

Method used

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  • Improved preparation of molecular imprinted polymers
  • Improved preparation of molecular imprinted polymers
  • Improved preparation of molecular imprinted polymers

Examples

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preparation example Construction

[0133] Therefore, it is evident from the above that the second aspect of the present invention derives a method for the preparation of a MIP having high binding capacity and specificity for a target molecule, which method comprises: Raw MIP (i.e. polymeric cross-linked MIP that does not substantially extract the template or does not adopt the structure of the micronized MIP) of the template molecule composed of the material, undergoes a first step of micronization so that the resulting MIP particles are small enough to remove / extract the template molecule, removing / extracting substantially all of the template molecules, optionally subjecting the MIP thus obtained to a second micronization step, wherein said first and optionally second micronization steps result in a MIP having an average diameter of at most 25 μm . After these processes, the resulting MIPs have a higher ratio of volume to exposed binding sites. Usually it is sufficient (easiest) to use only the first microniz...

Embodiment 1

[0183] Fluorescein-templated MIP

[0184] In a 100ml flask, 1.4ml methacrylic acid (MAA) monomer, 9.5ml ethylene glycol dimethacrylate (EGDMA), 50mg fluorescein and 10ml tetrahydrofuran (THF) were placed in a hot water bath (about 40°C) Mix for 30 minutes. 2 g of 1,1-azobis(cyclohexane-carbonitrile) (ACHCN) were added slowly. After dissolution the solution was purged with argon (THF sat'd) for 15 minutes. Polymerization was initiated by continuous UV light (365 nm, 9 W) irradiation for 48 h. The resulting polymer was yellow and brittle and was micronized by hand in a mortar to a particle size between 10 and 25 μm. The powder was refluxed in THF for 30 minutes, washed in ethanol / THF (75:25) and filtered several times. Air-dried white powder.

Embodiment 2

[0186] MIP templated with cholic acid

[0187] In a 100 ml flask, 1.4 ml methacrylic acid (MAA) monomer, 9.5 ml ethylene glycol dimethacrylate (EGDMA), 2 g cholic acid and 12 ml tetrahydrofuran (THF) were mixed in a hot water bath for 30 minutes. 0.2 g of 2,2'-azobisisobutyronitrile / 2,2'-azobis-(2-methylpropionitrile) (AIBN) was added slowly. After dissolution the solution was purged with argon (THF sat'd) for 15 minutes. Polymerization was initiated by continuous UV light (365 nm, 9 W) irradiation for 24 h in an ice bath. The resulting polymer was yellow rigid and micronized by hand in a mortar to a particle size between 25 and 50 μm. The powder was refluxed in THF for 30 minutes, washed and filtered 4 times in ethanol / THF (75:25). The white powder was air dried overnight.

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Abstract

One aspect is a method for improved preparation of molecular imprinted polymer (MIP) particles, where initial compositions comprising insoluble MIP particles are enriched for those MIP particles that bind a particular target molecule, thus excluding non-binding and weakly binding particles from the final composition. Enrichment is typically accomplished via use of chromatographic methods capable of separating particulate material or by means of agglutination. Another aspect is preparation of improved insoluble MIPs by use of extended micronization of raw MIP particles with a view to expose a large number of binding sites per mass unit of MIP particles. In preferred embodiments the two aspects are combined. The resulting improved MIPs may be used for diagnostic, analytical and therapeutic purposes, notably as orally administered drugs which can bind substances such as cholesterol and bile acids and bile acid salts in the gastrointestinal tract.

Description

technical field [0001] The present invention relates to improvements in the preparation of molecularly imprinted polymers (MIPs), and in particular to methods of increasing the binding and specificity of MIPs to facilitate their use as capture agents in pharmaceutical formulations, especially for binding targets in the gastrointestinal tract Pharmaceutical preparations of molecules such as cholesterol and bile acids and bile salts. Furthermore, improvements in the preparation of MIPs can serve as a means of characterizing said MIPs. Background technique [0002] Molecular imprinting of synthetic polymers is the process of copolymerization of functionally crosslinked monomers in the presence of target molecules as molecular templates. Prior to polymerization, the functional monomer is either non-covalently bound to the template to form a complex, or covalently coupled to form a polymerizable derivative of the template. After polymerization, the functional groups of the mono...

Claims

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Application Information

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IPC IPC(8): B01J20/26A61K31/74C08J9/00
CPCB01J20/26B01J20/3057B01J20/268
Inventor 杰斯波·斯卫宁·克里斯藤森克劳斯·格利高里斯·尼尔森尼古拉斯·奥托·克罗赫
Owner MIPSALUS APS
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