Method for the preparation of macroporous particles and macroporous

Patent metadata

Field	Value
Publication number	US-2015291760-A1
Application number	US-201314439438-A
Country	US
Kind code	A1
Filing date	Nov 22, 2013
Priority date	Nov 26, 2012
Publication date	Oct 15, 2015
Grant date	—

Abstract

A method for producing macro porous micro-clusters is proposed comprising at least the following individual steps in given order: a) synthesis of dispersed cross-linked polymeric latex primary particles starting from at least one monomer or oligomer using emulsion polymerization; b) swelling of the primary particles with a liquid comprising at least an additional charge of monomer and/or oligomer and a cross-linker, optionally further comprising functionalization agents; c) destabilization by increase of ionic strength (by adding a salt and/or acid and/or base) in a combination with application of shear, both being above the gel formation boundary of the phase diagram, until agglomerates composed of primary particles of the desired size are formed; d) polymerization of the agglomerates to form the macro porous micro-clusters. Furthermore the invention to relates to correspondingly produced micro-clusters and uses of such micro-clusters in particular for chromatographic purposes.

First claim

1 . A method for producing macro porous micro-clusters comprising at least the following individual steps in given order:
a) synthesis of dispersed cross-linked polymeric latex primary particles starting from at least one monomer or oligomer; b) swelling of said primary particles with a liquid comprising at least an additional charge of at least one of monomer, oligomer, and a cross-linker; c) destabilization by adding at least one of a salt, acid and base and concomitant application of shear until agglomerates of the particles of the desired size are formed; d) polymerization of the agglomerates to form the macro porous micro-clusters.

2 . The method for producing macro porous micro-clusters according to claim 1 , wherein in step c) the shear rate, expressed in l/second, and the ionic strength as given by the concentration of at least one of salt, acid and base, expressed in mol/ 1 , are adapted by measuring the phase diagram and selecting the shear rate and ionic strength to be both at or above the line of the phase boundary and in the gel phase therein.

3 . The method according to claim 2 , wherein for the measurement of the phase diagram the critical ionic strength value for no shear, the critical shear value for no salt/acid/base as well as at least one ionic strength value for a determined shear or at least one critical shear value for a determined ionic strength is determined, and the phase boundary is determined from these values using a numerical.

4 . The method according to claim 1 , wherein in step c) at least one of a salt, acid and base is added in an extent such that its concentration in a suspension comprising the particles is above the critical coagulation concentration,
or wherein in step c) concentration of at least one of salt, acid and base is chosen to be in the range of 1/10 to ½ of the critical coagulation concentration.

5 . The method according to claim 1 , wherein the shear in step c) is generated by passing the fluid through at least one micro-channel.

6 . The method according to claim 1 , wherein in step c) a shear rate in the range of 200-4000 l/second is applied and/or wherein in in step c) a shear rate in the range from 1×10 5 to 1.7×10 6 l/s.

7 . The method according to claim 1 , wherein in step c) the concentration of at least one of salt, acid and base, at least at the end of the step, is twice as high as the critical coagulation concentration.

8 . The method according to claim 1 , wherein in step c) the concentration of at least one of salt, acid and base is increased over time.

9 . The method according to claim 1 , wherein step c) is carried out for a time span of at least 5 minutes.

10 . The method according to claim 1 , wherein step d) is carried out for a time span of at least 1 hour.

11 . The method according to claim 1 , wherein the primary particles are core shell particles with a hard core.

12 . The method according to claim 1 , wherein in step b) a mixture of monomers or oligomers, together with a cross-linker system, is added, to the suspension obtained in step a).

13 . The method according to claim 1 , wherein in step c) a solid volume fraction below 10%, is used, in particular if aggregation is performed under fully destabilized Diffusion-Limited Cluster Aggregation conditions, and/or wherein in in step c) a solid volume fraction below 50%, is used.

14 . The method according to claim 1 , wherein the monomers and/or oligomers as used in at least one of step a) and b) are selected from the group forming nanoparticles using emulsion or mini-emulsion based methods.

15 . The method according to claim 1 , wherein the generated macro porous micro-clusters are surface functionalized, wherein the surface functionalization is generated by the functionalization agent present at least one of step b) and by a surface functionalization step carried out before or after step d).

16 . The method according to claim 1 , wherein the generated macro porous micro-clusters are coated, by a functional gel.

17 . A macro porous micro-cluster as obtained or as obtainable by a method according to claim 1 .

18 . The micro-cluster according to claim 17 , characterized in that it is essentially free from pores with a size below 20 nm.

19 . The micro-cluster according to claim 17 , wherein it has a radius of gyration in the range of 10-100 μm.

20 . The micro-cluster according to claim 17 , wherein it has a surface area SBET in the range of 5-30 m 2 per gram.

21 . Use of micro-clusters according to claim 11 for the separation of chemical compounds, with molecular weights in the range of 10-200 Dalton or of biopharmaceuticals.

22 . The method according to claim 1 , wherein step a) involves the synthesis of dispersed cross-linked polymeric latex primary particles starting from at least one monomer or oligomer based on at least one of styrene, acrylic, and vinyl acetate monomers in an emulsion polymerization.

23 . The method for producing macro porous micro-clusters according to claim 1 , wherein in step c) the shear rate, expressed in l/second, and the ionic strength as given by the concentration of at least one of salt, acid and base, expressed in mol/l, are adapted by measuring the phase diagram and selecting the shear rate and ionic strength to be both at or above the line of the phase boundary and in the gel phase therein, and wherein for the measurement of the phase diagram the critical ionic strength value for no shear, the critical shear value for no salt/acid/base as well as at least one ionic strength value for a determined shear or at least one critical shear value for a determined ionic strength is determined, and the phase boundary is determined from these values using a numerical, quadratic fitting, to determine the parameters a, b and c of the formula, wherein S is the shear rate and I is the ionic strength:
S fit =aI 2 +bI+c and selecting the shear rate (S) and the ionic strength (I) for step c) such that
S ( I )≧ S fit ( I ),

wherein the shear rate (S) and the ionic strength (I) for step c) are chosen such that
S ( I )> S fit ( I ).

24 . The method according to claim 1 , wherein in step c) the concentration of at least one of salt, acid and base is chosen to be in the range of ¼ to ⅓ of the critical coagulation concentration, wherein to eliminate undesired aggregate formation a salt/acid/base solution with a concentration equal to or lower than the corresponding CCC is mixed with the latex solution is used.

25 . The method according to claim 1 , wherein the shear in step c) is generated by passing the fluid through at least one micro-channel, wherein this micro-channel is a homogenizer with a z-shape of a rectangular cross-section, with a length of 3×10 −3 -7×10 −3 m, and a cross-sectional area of 3×10 −8 -7×10 −8 m 2 , under conditions of up to 1.7×10 6 l/s at up to 170 bar, with water.

26 . The method according to claim 1 , wherein in step c) a shear rate in the range of 300-3000 l/second is applied, if aggregation is performed under fully destabilized Diffusion-Limited Cluster Aggregation conditions,
and/or wherein in in step c) a shear rate in the range from 5×10 5 up to 1.7×10 6 l/s is applied, if aggregation is performed under partially destabilized Reaction-Limited Cluster Aggregation conditions.

27 . The method according to claim 1 , wherein in step c) the concent

Assignees

• Eth Zuerich

Inventors

• Storti Giuseppe
• Morbidelli Massimo
• Soos Miroslav
• Lamprou Alexandros
• Brand Bastian

Classifications

• C08F212/08 Primary

  Styrene · CPC title

• C08J2331/04

  Homopolymers or copolymers of vinyl acetate · CPC title

• C07K1/16

  by chromatography · CPC title

• B01J41/14

  obtained by reactions only involving unsaturated carbon-to-carbon bonds · CPC title

• C08J2333/00

  Characterised by the use of homopolymers or copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and only one being terminated by only one carboxyl radical, or of salts, anhydrides, esters, amides, imides, or nitriles thereof; Derivatives of such polymers · CPC title