WO2003091321A1 - Porous polymer material and method of production thereof - Google Patents

Abstract

According to the present invention, there is provided a porous polymer material and a method of production thereof, where a large majority, for example 80 % or more, or even up to about 100 % of the material is in the form of substantially spherical beads with narrow bead size distributions. These polymeric beads have a porous structure, characterized by cavities joined by interconnecting pores (a HIPE structure), some of which are connected to the surface of the bead.

Description

DESCPJPTION POROUS POLYMER MATERIAL AND METHOD OF PRODUCTION THEREOF

Crosslinked porous polymeric materials have been used for a variety of

applications and have proved especially useful to the biomedical field, being used as label or

sensing-device carriers. Other uses include affinity chromatography, immobilisation of enzymes,

drug delivery and solid-phase synthesis of proteins.

U.S. Pat. No. 4,522,953, discloses crosslinked porous polymeric materials produced by

polymerization of water-in-oil (W/O) high internal phase emulsions (HIPEs) where the ratio of

oil to water is typically greater than 70% (P. Hainey, et al, Macromolecules 1991, 24, 117; N.

R. Cameron, et al., Adv. Polym. Sci. 1996, 126, 163; A. Barbetta, et al, Chem. Commun. 2000,

221). The HIPEs comprise a combination of a substantially water-insoluble monomer and a

substantially water-insoluble crosslinker as the continuous phase (e.g., styrene/divinylbenzene)

and an aqueous discontinuous phase. Polymerization of the HIPE, usually by thermal free-

radical initiation, followed by removal of the discontinuous phase leads to a porous material that

is a replica of the original emulsion. The disclosed polymers have rigid porous structures

characterized by cavities that are interconnected by pores in the cavity walls. The disclosed

materials were hydrophobic but could be made hydrophilic by suitable surface functionalization

as discussed in U.S. Pat. Nos. 4,536,521; 4,611,014 and 4,612,334.

The original process for synthesizing HIPE polymers produced monolith blocks of material

that conformed to the dimensions of the reaction vessel {i.e., the materials were 'molded'). A

significant disadvantage is that it is very difficult to remove the discontinuous phase from these

large continuous objects. Furthermore, this product morphology is only useful for certain applications. The materials can be reduced to particles by grinding, but this is expensive and

leads to particles with irregular shapes and sizes.

The direct formation of HIPE polymers in the form of microbeads was disclosed in U.S. Pat.

No. 5,583,162 and WO95/33553. The disclosed HIPE microbeads are produced by

polymerization of a suspension of HIPE droplets.

The direct polymerization of hydrophilic monomers in an "oil-in- water-in-oil" emulsion is

described in U.S. Pat. No. 4,742,086. The emulsions comprise of less than 70% internal oil

phase, and are therefore not HIPE microbeads.

U.S. Pat. Nos. 5,653,992; 5,760,097; 5,863,957; 6,048,908; 6,100,306 and 6,218,440

disclose the direct synthesis of HIPE microbeads by polymerization of suspensions of HIPE

droplets. The materials disclosed are either hydrophobic or hydrophilic in nature. In general,

W/O HIPEs comprising substantially oil-soluble monomers lead to hydrophobic HIPE

microbeads, while oil-in-water (O/W) HIPEs comprising substantially water-soluble monomers

lead to hydrophilic HIPE microbeads.

A general disadvantage associated with the direct suspension polymerization of HIPE

droplets is that particles are produced with a relatively broad size range. The rather broad

distribution of particle sizes and shapes produced by conventional suspension polymerization is

well known in the prior art (H. G. Yuan, et al, J. Macromol Sci., Rev. Macromol. Chem. Phys.

1991, C31, 215; R. Arshady, Colloid Polym. Sci. 1992, 270, 717; E. Vivaldo-Lima, et al, Ind.

Eng. Chem. Res. 1997, 36, 939). For example, U.S. Pat. No. 5,583,162 discloses that

approximately 10% of the microbeads were disclosed to be "substantially spherical or

substantially ellipsoid or a combination of the two".

One method for producing spherical polymer beads with much greater control over bead size is sedimentation polymerization (E. Ruckenstein, et al, Polymer 1995, 36, 2857; E.

Ruckenstein, et al, J. Appl Polym. Sci. 1996, 61, 1949). In this process, monomer droplets are

partially polymerized during sedimentation through an immiscible sedimentation medium. The

size distribution of the beads so produced may be very narrow because the droplets are spatially

isolated from one another during sedimentation. As such, droplet collision and exchange does

not occur. U.S. Pat. No. 6,277,932 discloses a reverse phase bead polymerization process that

resulted in good control over bead size products, although no materials were disclosed with a

porous HIPE structure.

It is an object of the present invention, to provide a porous polymer material and a method

of production thereof, where a large majority , for example 80% or more, or even up to about

100% of the material is in the form of substantially spherical beads with narrow bead size

distributions. These polymeric beads have a porous structure, characterized by cavities joined

by interconnecting pores (a HIPE structure), some of which are connected to the surface of the

bead.

The present invention overcomes or alleviates the problems associated with current

methods of producing porous polymer beads which result in beads of irregular shapes and sizes

being produced.

In accordance with the first aspect of the present invention, there are provided porous

crosslinked hydrophilic polymeric beads comprising;

a nominal void volume of 70% or greater;

an average diameter range of from about 0.25 mm to about 5 mm;

a standard deviation from the average diameter within the range of from about 0.1%) to

about 50%. It is preferred that from about 50% to about 100% of the beads are substantially spherical,

in addition to having a total pore volume of from about 1 ml/g to about 5 ml/g.

In a preferred embodiment, the average bead diameter of the hydrophilic beads ranges

from about 0.25 mm to about 5 mm. More preferably the average bead diameter ranges from

about 0.4 mm to about 3 mm and even more preferably from about 0.5 mm to about 2.5 mm.

The hydrophilic beads of the present invention possess many of the desirable properties

of prior art HIPE polymers. Specifically, the hydrophilic beads are characterized by having a low

density and a highly porous structure with cavities that are highly interconnected by a network

of pores. The nominal void volume in the hydrophilic beads is at least about 70%, preferably in

the range 75%-99%, and more preferably in the range 80%-95%. It will be apparent that the

bead morphology is suitable for use in a number of applications such as packed column

chromatography, catalyst supports, controlled release of active pharmaceuticals or other active

ingredients, cell immobilization, and rapid fluid absorption.

The bead size distribution is relatively narrow with the standard deviation in the average

bead diameter ranging from about 0.1% to about 50%. In a preferred embodiment of this

invention, the standard deviation in the average bead diameter ranges from about 0.5% to about

20%). In a most preferred embodiment of this invention, the standard deviation in the average

bead diameter ranges from about 1% to about 10%.

Preferably, in accordance with the present invention, about 50% to about 100% of the

beads are substantially spherical. In a further preferred embodiment of the present invention,

about 80%) to about 100%) of the beads are substantially spherical. In the most preferred

embodiment of the present invention, about 95% to about 100%) of the beads are substantially

spherical. The porous crosslinked hydrophilic polymeric beads described above have a total pore

volume of from about lml/g to about 5ml/g, more preferably from about 1.5 ml/g to about 3

ml/g, still more preferably from about 1.8 ml/g to about 2.8 ml/g.

Also in accordance with the present invention, there is provided a method for

producing porous crosslinked hydrophilic polymeric beads comprising;

forming an HIPE;

displacing the HIPE into a sedimentation medium which is substantially immiscible

with the HIPE in discrete, uniformly-sized droplets;

allowing the HIPE droplets to sediment in the sedimentation medium;

at least partially polymerizing the droplets during sedimentation;

and if necessary completing the polymerization of the droplets after sedimentation, to

form porous crosslinked hydrophilic beads.

The HIPE may be an O/W HIPE, in which case the aqueous continuous phase preferably

comprises a substantially water-soluble hydrophilic monomer. The monomer may be self cross-

linking. Alternatively, or as well, the aqueous continuous phase may comprise a substantially

water-soluble crosslinker. The aqueous continuous phase may additionally comprise a

polymerization initiator, and/or an emulsifier that will facilitate the formation of a stable O/W

HIPE. The sedimentation medium in this case is preferably non-aqueous.

Preferably, the droplets are only partially polymerized during sedimentation. However,

if so, polymerization should proceed during sedimentation to an extent sufficient to prevent

coalescence of the droplets in the sedimentation medium towards or at the end of sedimentation.

The method for producing the porous crosslinked hydrophilic polymeric beads may be

continuous or completed in batches, or indeed performed in a step-by-step process. It will be apparent to those skilled in the art, that displacing the emulsion as discrete,

uniformly sized droplets into a sedimentation medium and subsequent polymerization during

sedimentation, leads to beaded materials that possess an internal porous structure that is a skeletal

replica of the original HIPE, both in relation to the microscopic HIPE structure and the

macroscopic structure of the HIPE droplet templates. The bead morphology allows easy removal

of the internal, discontinuous oil phase. One such method of displacing the emulsion into a

sedimentation medium is by injection. It will also be apparent to those skilled in the art that the

average diameter of the hydrophilic bead can be controlled by variation of experimental factors

such as the diameter of the injection nozzle, the injection rate, and the viscosity of the HIPE.

In a preferred process according to the invention, the aqueous continuous phase

includes a monomer, a crosslinker, an initiator and an emulsifier. The non-aqueous

discontinuous phase may comprise light mineral oil and the sedimentation medium may

comprise a 10:1 v/v mixture of vegetable oil and light mineral oil.

The monomer can be selected from a wide range of substantially water-soluble

monofunctional vinyl monomers or mixtures of two or more thereof. Suitable vinyl

monomers include, for example, acrylamide; acrylic acid; sodium acrylate; methacrylic acid;

hydroxyethyl acrylate; hydroxyethyl methacrylate; sodium styrene sulfonate; vinyl pyridines;

vinyl pyrrolidones; N-methylmethacrylamide; N-acryloylmorpholine; and N-vinyl-N-

methacetamide. The monomer component is preferably present in the continuous phase in an

amount of from about 1% to about 80% by weight. The amount of the monomer component

is more preferably from about 10% to about 50% by weight, most preferably from about 20%>

to about 40% by weight.

The crosslinker can be selected from a wide range of substantially water-soluble polyfunctional vinyl monomers or mixtures of two or more thereof. Suitable crosslinkers

include, for example, NN'-methylene bisacrylamide; NN'-diallyl acrylamide; diallylamine;

diallyl methacrylamide; diallyl phthalate; diallyl malate; diallyl phosphate; divinyl sulfone;

diethylene glycol divinyl ether; ethylene glycol triacrylate; and ethylene glycol tetraacrylate.

Crosslinkers of this type can be used singly or as mixtures. The crosslinker component is

preferably present in the continuous phase an amount of from about 0.5% to about 20% by

weight. The amount of the crosslinker component is more preferably from about 1%> to about

15%) by weight, most preferably from about 5% to about 10%> by weight.

The initiator can be selected from a wide range of substantially water-soluble free-radical

initiators or mixtures of the two thereof. Suitable initiators include, for example, ammonium,

sodium, or potassium persulphate; sodium peracetate; and sodium percarbonate. The initiator

component is present in the continuous phase in an amount of from about 0.1% to about 5%> by

total weight of polymerizable monomer. The amount of the initiator component is more

preferably from about 0.5% to about 4% by total weight of polymerizable monomer, most

preferably from about 1% to about 2.5% by total weight of polymerizable monomer. Optionally,

a redox initiation promoter may also be added (for example, Ν,Ν,Ν,Ν-tetramethylethyldiamine)

either in the aqueous phase, the internal droplet phase, or in the sedimentation medium.

The emulsifier can be any nonionic, cationic, anionic, or amphoteric emulsifier, or

mixture of two or more thereof, effective to promote the formation of a stable O/W HIPE. In one

embodiment of the present invention, a mixture of sodium dodecyl sulphate and polyvinylalcohol

constitutes the emulsifier. In another embodiment of the present invention, a mixture of Triton

405 and polyvinylalcohol constitutes the emulsifier. The emulsifier component is present in the

continuous phase in an amount of from about 1% to about 60% by weight. The amount of the emulsifier component is more preferably from about 2% to about 40% by weight, most

preferably about 5% to about 25% by weight.

The oil discontinuous phase can be any substantially water-immiscible fluid that has a

boiling point that is significantly higher than the polymerization temperature. Suitable oil phases

include, for example, vegetable oil; light mineral oil; silicone oil; fluorocarbon oils; and higher

alkanes and mixtures of two or more thereof. The boiling point of the oil phase is greater than

about 50 °C, more preferably greater than about 70 °C, most preferably greater than about 90 °C.

The hydrophilic beads of the present invention are prepared from a HIPE, which comprises an

emulsion of an aqueous continuous phase (in which is dissolved monomer, crosslinker, and

initiator) and an oil discontinuous phase. The ratio of the two phases greatly affects the degree

of porosity in the hydrophilic bead and also the pore connectivity (i.e., the degree of openness

in the pore structure). In the present invention, it is preferable that the percentage of oil

discontinuous phase is in the range of from about 60% to about 96%>, more preferably from about

75% to about 92%, most preferably from about 80% to 90%.

After forming the HIPE, the HIPE is injected into a heated sedimentation medium in the form of discrete, uniformly sized droplets. It is an aspect of the present invention that the boiling point of the oil phase is greater than about 50 °C, more preferably greater than about 70 °C, most

preferably greater than about 90 °C. The rate of sedimentation of the HIPE droplets will be

determined in part by the viscosity of the sedimentation medium and the difference between the

density of the sedimentation medium and the average density of the HIPE droplets. If necessary,

the sedimentation rate can be decreased by addition of a high molecular weight linear polymer

that is miscible with the sedimentation medium (i.e., by increasing the viscosity). This viscosity

modifier can be any substantially water-insoluble natural or synthetic polymer that is miscible with the sedimentation medium. Alternatively, the sedimentation rate can be reduced by

introducing a counter-flow in the sedimentation medium in the upward direction (i.e. , against the

direction of droplet sedimentation). Alternatively, a mixed sedimentation medium can be used

to achieve the desired density and to precisely control the sedimentation velocity.

The HIPE can be prepared by utilising any of the methods outlined in the prior art, for

example, forming the HIPE by slowly adding the discontinuous phase to the continuous phase

while subjecting the mixture to efficient shear agitation. In one embodiment of the present

invention, the HIPE is prepared using a type Rwl 1 Basic IKA paddle stirrer.

In one process according to the present invention, the HIPE is injected into a vertically-

mounted sedimentation column containing a volume of a heated sedimentation medium. This

can be done by simple hand injection using a syringe. In a preferred embodiment of the

invention, the HIPE is injected continuously through a 0.6 mm x 25 mm nozzle at a constant rate

of 0.5 ml/min using a A-99 FZ Razel syringe pump. The droplet size can be varied by varying

the nozzle diameter, the HIPE viscosity, and the injection rate. In one example, the

sedimentation medium was heated to 90 °C, the height of the sedimentation column was 53 cm,

and the time taken for droplet sedimentation was approximately 5-20 seconds.

Partial polymerization of the HIPE droplets occurs during sedimentation. Upon arriving

at the bottom of the sedimentation column, the droplets are sufficiently rigid to prevent

agglomeration between droplets. Thus, no stabilizers are required in the sedimentation medium

to inhibit droplet coalescence. Polymerization is completed to form hydrophilic beads by heating

the partially polymerized droplets in the sedimentation medium or after recovery therefrom. In

a preferred embodiment where the monomer is acrylamide, the crosslinker is NN'-methylene

bisacrylamide, the free radical initiator is ammonium persulphate and the droplets are heated at 90 °C for a period of 2 h.

The polymerization stage converts the HIPE droplets into solid beads. The beads can be

recovered by decanting the sedimentation medium. Typically, the sedimentation medium can

be reused in subsequent polymerizations. The beads are washed with a solvent that is suitable

to remove traces of the sedimentation medium plus any unreacted monomer.

For example the hydrophilic beads can be washed in acetone. In one example, the

hydrophilic bead product was washed ten times with acetone. The discontinuous oil phase can

be removed by washing with any suitable solvent. In one further example, the discontinuous oil

phase was removed from the hydrophilic bead product by continuous extraction using

supercritical carbon dioxide (200 bar, 35 °C). In a preferred embodiment, the discontinuous oil

phase was removed by Soxhlet extraction using cyclohexane (15 h). Residual washing solvent

and any residual water are removed by drying under vacuum.

The porous hydrophilic beads according to the present invention and the process of the

invention, will now be more particularly described, by way of example only, with reference to the accompanying examples and drawings

Figure la is an optical microscope image of example 1.

Figure lb is an optical microscope image of example 2.

Figure lc is an optical microscope image of example 4.

Figure Id is an optical microscope image of example 5.

Figure 2 illustrates an electron micrograph of the internal structure of one bead in

example 1.

Figure 3 illustrates an electron micrograph of the bead surface of example 7.

Figure 4 illustrates an electron micrograph of the bead surface of example 8. Figure 5 illustrates an electron micrograph of internal structure of the bead in example

8.

Figure 6 is an optical image of the beads produced in example 6.

Figure 7 is an optical image of the beads produced in example 7.

Figure 8 is an optical image of the beads produced in example 8.

Example 1

Hydrophilic HIPE beads were prepared by continuous sedimentation polymerisation of a HIPE comprising an aqueous continuous phase (containing the monomer) and an oil discontinuous

phase. The components and amounts used in this study are indicated in Table 1 below. The components of the hydrophilic monomer phase were mixed in a beaker by stirring at room

temperature. After adding the surfactant (sodium dodecyl sulphate) and the co-surfactant

(polyvinylalcohol, MW = 9,000-10,000 g/mol, 80%> hydrolysed), the initiator (ammonium persulphate) was added. The aqueous monomer phase was stirred mechanically while slowly

adding light mineral oil to form a HIPE.

A glass sedimentation column (53 cm in length, outside diameter 5.6 cm, internal diameter 4.6 cm) was used. Light mineral oil and vegetable oil (1 :10 v/v) was added and this

mixed oil was used as the sedimentation medium. The level of the oil was 5 cm from the top of

the glass column. The sedimentation medium was heated to 90 °C. The HIPE was injected using

a A-99 FZ Razel syringe pump through a 0.6 mm x 25 mm needle at a flow rate of 0.5 ml/min.

After the injection of the HIPE, the partially gelled beads were collected at the bottom

of the sedimentation column. Complete polymerization of the beads was achieved by heating

the column for 2.5 h at 90 °C.

The collected beads were washed ten times with acetone and allowed to dry in air at room temperature. The internal oil phase was removed by Soxhlet extraction with cyclohexane for 15

h. The beads were then dried overnight in a vacuum oven at 50 °C.

The beads have a skeletal density very similar to that of the equivalent non-porous cross-

linked polymer, which suggests that the pores are interconnected and that there is little closed

porosity.

Figure 1 shows an optical microscope image of a range of beads relating to examples 1,

2, 4 and 5. The mean bead diameter of figure la is 1.56 mm and the standard deviation in bead

diameter is 8.2 %. The mean bead diameter of figure lb is 1.61 mm and the standard deviation

in bead diameter is 6.96%). The total pore volume in figure lb is 2.14 ml/g. The mean bead diameter of figure lc is 1.20 mm and the standard deviation in bead diameter is 12.60%>. The mean bead diameter of figure Id is 1.63 mm and a standard deviation in bead diameter is 10.75%)

Figure 2 shows an electron micrograph of a fractured bead, showing the internal structure

of the bead of example 1 (x2000 magnification). The BET surface area of the beads was 5.98

ml/g. The total pore volume (or intrusion volume) as measured by mercury intrusion porosimetry was 2.51 ml/g.

Figure 3 illustrates an electron micrograph of the bead surface of example 7. Figure 7 is

an optical microscope image of example 7, beads of which has a mean bead diameter of 2.19 mm and a standard deviation in bead diameter of 12.23%.

Figure 4 illustrates an electron micrograph of the bead surface of example 8, Figure 5 shows the internal structure of the bead in example 8 and Figure 8 is an optical microscope image

of example 8 which has a mean bead diameter of 2.24 mm and a standard deviation in bead

diameter of 11.95 %.

Figure 6 is an optical microscope image of example 6, which has a mean bead diameter of 1.51mm and a standard deviation in bead diameter of 8.86%>.

Figure 7 is an optical microscope image of example 7, beads of which had a mean bead diameter of 2.19 mm and a standard deviation in bead diameter of 12.23%

Table 1: HIPE Components for Example 1

(1) Aqueous monomer/crosslinker solution

Acrylamide : 15.36 g

N N -methylene bisacrylamide: 3.11 g

Deionized water: 40 ml

(2) 1.5 ml of the above solution was emulsified with:

Sodium dodecyl sulphate: 0.60 g

Polyvinylalcohol, MW = 9,000-10,000: 0.06 g Ammonium persulphate: 0.025 g

Light mineral oil: 6.0 ml

(3) Sedimentation Medium:

Vegetable oil: 770 ml

Light mineral oil: 70 ml

Temperature: 90 °C

Examples 2-8

Exemplary preferred FIIPE beads were prepared according to the following general protocol. The details of specific examples are set forth in Table 2-8.

1. An aqueous hydrophilic monomer solution was prepared. 2. The surfactant, co-surfactant, and initiator were added step-wise, with stirring.

3. The discontinuous oil phase was added with mechanical stirring to form a HIPE.

4. The emulsion was injected into the heated oil sedimentation medium as discrete,

uniformly sized droplets.

5. After partial gelation during sedimentation, the beads were collected at the bottom of the sedimentation column. Polymerization was completed over a period of 2.5 h at 90 °C.

6. The beads were separated form the sedimentation medium by decanting and washed

10 times with acetone. The internal oil phase was extracted form the beads using cyclohexane in a Soxhlet extractor for approximately 15 h.

7. The beads were dried in a vacuum oven at 50 °C overnight.

Table 2: HIPE Components for Example 2

(1) Aqueous monomer/crosslinker solution

Acrylamide: 15.36 g

NN'-methylene bisacrylamide: 3.11 g

Deionized water: 40 ml

(2) 1.5 ml of the above solution was emulsified with:

Sodium dodecyl sulphate: 0.60 g

Polyvinylalcohol, MW = 9,000-10,000: 0.03 g Ammonium persulphate: 0.025 g Light mineral oil: 6.0 ml

(3) Sedimentation Medium:

Vegetable oil: 770 ml

Light mineral oil: 70 ml Temperature: 90 °C

Mean bead diameter = 1.61 mm. Standard deviation in bead diameter = 6.96%. Total pore volume (intrusion volume) = 2.14 ml/g.

Table 3: HIPE Components for Example 3

(1) Aqueous monomer/crosslinker solution

Acrylamide: 15.36 g

NN'-methylene bisacrylamide: 3.11 g

Deionized water: 40 ml

(2) 1.5 ml of the above solution was emulsified with: Sodium dodecyl sulphate: 0.20 g Polyvinylalcohol, MW = 9,000-10,000: 0.08 g Ammonium persulphate: 0.025 g

Light mineral oil: 8.5 ml

(3) Sedimentation Medium:

Vegetable oil: 770 ml

Light Mineral oil: 70 ml

Temperature: 90 °C

Mean bead diameter = 1.53 mm. Standard deviation in bead diameter = 23.03%. Total pore volume (intrusion volume) = 2.65 ml/g.

Table 4: HIPE Components for Example 4 (1) Aqueous monomer/crosslinker solution

Aery lamide : 15.36 g

NN'-methylene bisacrylamide: 3.11 g

Deionized water: 40 ml

(2) 1.5 ml of the above solution was emulsified with: Sodium dodecyl sulphate: 0.25 g Polyvinylalcohol, MW = 9,000-10,000: 0.05 g

Ammonium persulphate: 0.030 g

Light mineral oil: 8.5 ml

(3) Sedimentation Medium:

Vegetable oil: 770 ml

Light mineral oil: 70 ml

Temperature: 90 °C

Mean bead diameter = 1.20 mm. Standard deviation in bead diameter = 12.60%.

Table 5: HIPE Components for Example 5

(1) Aqueous monomer/crosslinker solution

Acrylic Acid: 15.36 g

N N'-methylene bisacrylamide : 3.10 g

Deionized water: 40 ml

(2) 1.5 ml of the above solution was emulsified with:

Sodium dodecyl sulphate: 0.40 g

Polyvinylalcohol, MW = 9,000-10,000: 0.06 g Ammonium persulphate: 0.036 g

N,N,N,N-Tetramethylethylenediamine: 50 μL

Light mineral oil: 6.0 ml

(3) Sedimentation Medium:

Vegetable oil: 770 ml

Light mineral oil: 70 ml

Temperature: 90 °C

Mean bead diameter = 1.63 mm. Standard deviation in bead diameter = 10.75%.

Table 6: HIPE Components for example 6

(1) Aqueous monomer/crosslinker solution:

Aery lamide : 15.36 g

Ν, Ν'-methylene bisacrylamide: 3.11 g

Polyvinylalcohol, MW = 9,000-10,000 2.50 g

Deionized water: 40 ml

(2) 3.0 ml of the above solution was emulsified with: Sodium dodecyl sulphate, 98%: 0.80 g

Light mineral oil: 14.0 ml Ν,Ν,Ν,Ν-Tetramethylethylenediamine: 1 drop in oil

(using 0.6mm X 25mm needle) Ammonium persulphate 10 wt % aqueous solution 0.40 ml

(3) Sedimentation medium:

Vegetable oil: 770 ml Light mineral oil: 70 ml

Temperature: 90 °C

Mean bead diameter = 1.51 mm. Standard deviation in bead diameter =

8.86 %.

Table 7: HIPE Components for example 7

(1) Aqueous monomer/crosslinker solution:

Aery lamide : 15.36 g

N, N'-methylene bisacrylamide: 3.11 g

Polyvinylalcohol, MW = 9,000-10,000 2.50 g

Deionized water: 40 ml

(2) 3.0 ml of the above solution was emulsified with: Sodium dodecyl sulphate, 98%: 0.70 g Light mineral oil : 12.0 ml

N,N,N,N-Tetramethylethylenediamine: 1 drop in oil

(using 0.6mm X 25mm needle)

Ammonium persulphate 10 wt %> aqueous solution 0.45 ml

(3) Sedimentation medium:

Light mineral oil: 750 ml

Heavy mineral oil: 200 ml

N,N,N,N-Tetramethy lethylenediamine : 23.0 ml

Temperature: 60 °C Mean bead diameter = 2.19 mm. Standard deviation in bead diameter =

12.23 %.

Table 8: HIPE Components for example 8

(1) Aqueous monomer/crosslinker solution:

Aery lamide : 15.36 g

N, N'-methylene bisacrylamide: 3.11 g

Polyvinylalcohol, MW = 9,000-10,000 2.50 g

Deionized water: 40 ml

(4) 3.0 ml of the above solution was emulsified with:

Sodium dodecyl sulphate, 98%o: 0.65 g Light mineral oil : 10.50 ml N,N,N,N-Tetramethylethylenediamine: 1 drop in oil

(using 0.6mm X 25mm needle)

Ammonium persulphate 10 wt % aqueous solution 0.45 ml

(5) Sedimentation medium:

Light mineral oil: 750 ml

Heavy mineral oil: 200 ml

N,N,N,N-Tetramethylethylenediamine: 23.0 ml

Temperature: 60 °C

Mean bead diameter = 2.24 mm. Standard deviation in bead diameter = 11.95 %.

Claims

1. Porous crosslinked hydrophilic polymeric beads comprising;

a nominal void volume of 70% or greater;

an average diameter range of from 0.25 mm to 5 mm;

a standard deviation from the average diameter within the range of from 0.1% to 50%.

2. A porous crosslinked hydrophilic polymeric bead described in claim 1 wherein from 50%>

to 100%) of the beads are substantially spherical.

3. A porous crosslinked hydrophilic polymeric bead described in claim 1 and claim 2, wherein

the total pore volume range from 1 ml/g to 5 ml/g.

4. A method for producing porous crosslinked hydrophilic polymeric beads comprising;

forming an HIPE;

displacing the HIPE into a sedimentation medium which is substantially immiscible with the

HIPE in discrete, uniformly-sized droplets;

allowing the HIPE droplets to sediment in the sedimentation medium;

at least partially polymerizing the droplets during sedimentation;

and if necessary completing the polymerization of the droplets after sedimentation, to form

porous crosslinked hydrophilic beads.

5. A method for producing porous crosslinked hydrophilic polymeric beads according to

claim 4, wherein the process is continuous.

6. A method for producing porous crosslinked hydrophilic polymeric beads according to

claim 5, wherein the monomer is selected from one the following group of vinyl monomers

or is a mixture of two or more thereof; acrylamide; acrylic acid; sodium acrylate; methacrylic

acid; hydroxyethyl acrylate; hydroxyethyl methacrylate; sodium styrene sulfonate; vinyl

pyridines; vinyl pyrrolidones; N-methylmethacrylamide; N-acryloylmorpholine; and N-vinyl-

N-methacetamide .

7. A method for producing porous crosslinked hydrophilic polymeric beads as claimed in

claims 4 to 6, wherein the monomer component is present in the continuous phase in an amount

ranging from 1%> to 80% by weight.

8. A method for producing porous crosslinked hydrophilic polymeric beads as claimed in

claims 4 to 7, wherein the crosslinker is selected from one of the following group of crosslinkers

or is a mixture of two or more thereof;

NN'-methylene bisacrylamide; NN'-diallyl acrylamide; diallylamine; diallyl methacrylamide;

diallyl phthalate; diallyl malate; diallyl phosphate; divinyl sulfone; diethylene glycol divinyl

ether; ethylene glycol triacrylate; and ethylene glycol tetraacrylate.

9. A method for producing porous crosslinked hydrophilic polymeric beads as claimed in

claims 4 to 8, wherein the crosslinkers component is present in the continuous phase in an

amount ranging from 0.5% to 20% by weight.

10. A method for producing porous crosslinked hydrophilic polymeric beads as claimed in claims 4 to 9, wherein the initiator can be selected from one of the following group of initiators

or is a mixture of two or more thereof; ammonium; sodium; or potassium persulphate; sodium

peracetate; and sodium percarbonate.

11. A method for producing porous crosslinked hydrophilic polymeric beads as claimed in

claims 4 to 10, wherein the initiator component is present in the continuous phase in an

amount ranging from 0.1%) to 5% by total weight of polymerizable monomer.

12. A method for producing porous crosslinked hydrophilic polymeric beads as claimed in

claims 4 to 11, wherein the emulsifier can be selected from one of the following groups of

emulsifiers or is a mixture of two or more thereof;

nonionic; cationic; anionic; and amphoteric.

13. A method for producing porous crosslinked hydrophilic polymeric beads as claimed in

claims 4 to 12, wherein the emulsifier component is present in the continuous phase in an amount

ranging from 1%> to 60%) by weight.

14. A method for producing porous crosslinked hydrophilic polymeric beads as claimed in

claims 4 to 13, wherein the oil discontinuous phase comprise any substantially water-immiscible

fluids selected from one of the following group or is a mixture of two or more thereof;

vegetable oil; light mineral oil; silicone oil; fluorocarbon oils; and higher alkanes.

15. A method for producing porous crosslinked hydrophilic polymeric beads as claimed in claims 4 to 14, wherein the percentage of oil in the discontinuous phase is in an amount ranging

from 60% to 96%.

16. A method for producing porous crosslinked hydrophilic polymeric beads as claimed in

claims 4 to 15, wherein the sedimentation rate is decreased by addition of a high molecular

weight linear polymer that is miscible with the sedimentation medium.

17. A method for producing porous crosslinked hydrophilic polymeric beads as claimed in

claims 4 to 16, wherein the beads are washed in acetone.

18. A method for producing porous crosslinked hydrophilic polymeric beads as claimed in

claims 4 to 17, wherein the discontinuous oil phase is removed from the hydrophilic polymeric

beads by continuous supercritical carbon dioxide extraction.

19. A method for producing porous crosslinked hydrophilic polymeric beads as claimed in

claims 4 to 17, wherein the discontinuous oil phase is removed from the hydrophilic polymeric

beads by Soxhlet extraction using cyclohexane.

20. A porous crosslinked hydrophilic polymeric bead and method of production as substantially

as herein described with reference to and as illustrated in the accompanying examples and

drawings.