# US 9,433,904 B2 · Cellulose hydrate membrane, method for the production thereof, and use thereof

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- Number: US 9,433,904 B2
- Document ID: US9433904B2
- Status: Granted
- Kind: B2
- Application number: 12/937,847
- Filed: 2009-02-10
- Published: 2011-06-23
- Granted: 2016-09-06
- Earliest claimed: 2008-04-14
- Assignees: Sartorius Stedim Biotech GmbH
- Applicants: Wolfgang Demmer; René Faber; Hans-Heinrich Hörl; Csilla Kiss; Dietmar Nuβbaumer
- Inventors: Wolfgang Demmer; René Faber; Hans-Heinrich Hörl; Csilla Kiss; Dietmar Nuβbaumer
- Web page: https://patentgrep.com/patent/US9433904B2

## CPC

- B01D 67/00931: {by introduction of specific groups after membrane formation, e.g. by grafting}
- B01D 69/02: characterised by their properties
- B01D 71/10: Cellulose; Modified cellulose
- B01J 20/262: {obtained otherwise than by reactions only involving carbon to carbon unsaturated bonds, e.g. obtained by polycondensation (macromolecular compounds obtained otherwise than by reactions only involving unsaturated carbon-to-carbon bonds per se C08G)}
- B01J 20/265: {modified or post-treated polymers (polymer carriers or substrates subjected to further impregnating or coating B01J20/3208)}
- B01J 20/267: {Cross-linked polymers}
- B01J 20/28033: {Membrane, sheet, cloth, pad, lamellar or mat}
- B01J 20/28069: {Pore volume, e.g. total pore volume, mesopore volume, micropore volume}
- B01J 20/28078: {Pore diameter}
- B01J 20/285: based on polymers
- B01J 20/286: Phases chemically bonded to a substrate, e.g. to silica or to polymers
- C07K 1/30: by precipitation
- B01D 2323/16: Swelling agents
- B01D 2323/30: Cross-linking
- B01D 2323/36: Introduction of specific chemical groups
- B01D 2325/0283: Pore size
- B01D 2325/12: Adsorbents being present on the surface of the membranes or in the pores
- B01D 2325/14: Membrane materials having negatively charged functional groups
- B01D 2325/16: Membrane materials having positively charged functional groups
- B01D: SEPARATION (separating solids from solids by wet methods B03B, B03D; by pneumatic jigs or tables B03B; by other dry methods B07; magnetic or electrostatic separation of solid materials from solid materials or fluids, separation by high-voltage electric fields B03C; centrifuges, vortex apparatus B04; presses per se for squeezing-out liquid from liquid-containing material B30B9/02; treatment of water C02F, e.g. softening by ion-exchange C02F1/42; {arrangements of air intake cleaners in gas turbine plants F02C7/05} ; arrangements or mounting of filters in air-conditioning, air-humidification or ventilation F24F13/28)
- B01J: CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)

## Abstract

There is provided a cellulose hydrate membrane having a porous double structure which consists of micropores having a diameter in the range from >100 nm to 20 μm and ultrapores which have a diameter of <100 nm and which are not accessible to Blue Dextran having an average molecular weight Mw of 2 000 000, wherein the fraction of the volume of the ultrapores is more than 15% of the entire pore volume accessible to water. In addition, a method for producing the membrane, its use as an adsorption membrane, and an apparatus for membrane chromatography are specified.

## Claims

### Claim 1

A crosslinked cellulose hydrate membrane having a porous double structure consisting of
micropores having a diameter in the range from >100 nm to 20 μm, and
ultrapores which have a diameter of <100 nm and which are not accessible to Blue Dextran having an average molecular weight Mw of 2 000 000, wherein the fraction of the volume of the ultrapores is more than 15% of the entire pore volume accessible to water,
wherein the crosslinked cellulose hydrate membrane is obtained by a method comprising:
providing a cellulose ester membrane having a pore diameter in the range from 0.1 to 20 μm;
hydrolyzing the cellulose ester membrane under a swelling condition; and
crosslinking the hydrolyzed cellulose ester membrane;
wherein the hydrolysis and the crosslinking are carried out separately, and;
the hydrolysis is carried out in a hydrolysis medium consisting of water and one or both of sodium hydroxide and lithium hydroxide, wherein the concentration of one or both of sodium hydroxide and lithium hydroxide in the hydrolysis medium is in the range of 0.4 to 10% by weight, based on the hydrolysis medium.

### Claim 2 (depends on 1)

The crosslinked cellulose hydrate membrane as claimed in claim 1, wherein the micropores which stretch from a first main surface of the membrane through the membrane to a second main surface are connected with formation of channels communicating with one another, and the ultrapores stretch from an inner surface of the micropores into a material forming the structure of the membrane, forming a dead end, and/or connect neighboring micropores with one another.

### Claim 3 (depends on 1)

The crosslinked cellulose hydrate membrane as claimed in claim 1, wherein at least one functional group is bonded to the membrane.

### Claim 4 (depends on 3)

The crosslinked cellulose hydrate membrane as claimed in claim 3, wherein the at least one functional group is/are ligand(s) which is/are capable of entering into interactions with adsorbates present in fluids.

### Claim 5 (depends on 4)

The crosslinked cellulose hydrate membrane as claimed in claim 4, wherein the ligands comprise anionic and cationic groups.

### Claim 6 (depends on 5)

The crosslinked cellulose hydrate membrane as claimed in claim 5, wherein the cationic groups are selected from the group consisting of primary, secondary, tertiary, and/or quaternary amines.

### Claim 7 (depends on 6)

The crosslinked cellulose hydrate membrane as claimed in claim 6, wherein the primary, secondary, and/or tertiary amines are polymeric compounds having linear and/or branched and/or cyclic structures.

### Claim 8 (depends on 7)

The crosslinked cellulose hydrate membrane as claimed in claim 7, wherein the polymeric compounds are selected from the group consisting of polyalkyleneimines having a molar mass in the range from 800 to 1 000 000 g/mol.

### Claim 9 (depends on 7)

The crosslinked cellulose hydrate membrane as claimed in claim 7, wherein the polymeric compounds are selected from the group consisting of polyallylamines having a molar mass in the range from 3000 to 150 000 g/mol.

### Claim 10 (depends on 7)

The crosslinked cellulose hydrate membrane as claimed in claim 7, wherein the polymeric compounds are selected from the group consisting of polyvinylamines having a molar mass in the range from 5000 to 500 000 g/mol.

### Claim 11 (depends on 7)

The crosslinked cellulose hydrate membrane as claimed in claim 7, wherein the polymeric compound is polymyxin B.

### Claim 12 (depends on 7)

The crosslinked cellulose hydrate membrane as claimed in claim 7, wherein at least one primary, secondary, or tertiary amine group is reacted with a component selected from the group comprising phenyl glycidyl ether, 1,2-epoxyethylbenzene, dodecyl glycidyl ether, tetradecyl glycidyl ether, benzyl chloride, (3-glycidyloxypropyl)trimethoxysilane, bis[(4-glycidyloxy)phenyl]methane, bisphenol A diglycidyl ether, 1,4-butanediol diglycidyl ether, 6-hexanediol diglycidyl ether, N,Ndiglycidyl-4-glycidyloxyaniline, 4,4′-methylenebis(N,N-diglycidylaniline), and/or tris(4-hydroxyphenyl)methane triglycidyl ether.

### Claim 13 (depends on 5)

The crosslinked cellulose hydrate membrane as claimed in claim 5, wherein the anionic groups are selected from the group consisting of sulfonic and carboxylic acids.

### Claim 14 (depends on 4)

The crosslinked cellulose hydrate membrane as claimed in claim 4, wherein the ligands are affinity ligands.

### Claim 15 (depends on 14)

The crosslinked cellulose hydrate membrane as claimed in claim 14, wherein the affinity ligands are selected from the group consisting of benzamidines, biomimetic ligands, and/or proteins.

### Claim 16 (depends on 4)

The crosslinked cellulose hydrate membrane as claimed in claim 4, wherein the ligands are selected from the group consisting of metal chelates.

### Claim 17 (depends on 4)

The crosslinked cellulose hydrate membrane as claimed in claim 4, wherein the ligands are selected from the group consisting of reactive epoxide, aldehyde, azlactone, N-hydroxysuccinimide, and/or carbodiimide groups.

### Claim 18 (depends on 4)

The crosslinked cellulose hydrate membrane as claimed in claim 4, wherein the ligand is a catalyst.

### Claim 19 (depends on 4)

The crosslinked cellulose hydrate membrane as claimed in claim 4, wherein at least two structurally different ligands are bonded to the membrane.

### Claim 20 (depends on 3)

The crosslinked cellulose hydrate membrane as claimed in claim 3, wherein the at least one functional group is part of a spacer which is bonded to the cellulose hydrate membrane.

### Claim 21 (depends on 20)

The crosslinked cellulose hydrate membrane as claimed in claim 20, wherein the spacer is an oligomer or a polymer.

### Claim 22 (depends on 1)

A method for producing a crosslinked cellulose hydrate membrane having a porous double structure as claimed in claim 1, comprising:
providing a cellulose ester membrane having a pore diameter in the range from 0.1 to 20 μm,
optionally pretreating the cellulose ester membrane in a medium at a temperature in the range from about 20° C. to about 100° C, and
hydrolyzing the optionally pretreated cellulose ester membrane under swelling condition, wherein the hydrolysis is carried out in a hydrolysis medium consisting of water and one or both of sodium hydroxide and lithium hydroxide, wherein the concentration of one or both of sodium hydroxide and lithium hydroxide in the hydrolysis medium is in the range of 0.4 to 10% by weight, based on the hydrolysis medium, and
crosslinking the hydrolyzed cellulose ester membrane;
wherein the hydrolysis and the crosslinking are carried out separately.

### Claim 23 (depends on 22)

The method as claimed in claim 22, wherein a temperature of the hydrolysis medium during the hydrolysis is in the range from 10° C up to a boiling point of the hydrolysis medium.

### Claim 24 (depends on 22)

The method as claimed in claim 22, wherein the hydrolysis is carried out in a period in the range from about 0.1 to about 60 minutes.

### Claim 25 (depends on 22)

The method as claimed in claim 22, wherein the crosslinking is carried out with at least one crosslinking agent which comprises at least 2 functional groups in a molecule which are reactive with hydroxyl groups of the cellulose.

### Claim 26 (depends on 25)

The method as claimed in claim 25, wherein the crosslinking agent is selected from the group consisting of diepoxide compounds, diisocyanates, epichlorohydrin, epibromohydrin, dimethylurea, dimethylethyleneurea, dimethylchlorosilane, bis(2-hydroxyethyl) sulfone, divinyl sulfone, alkylene dihalogen, hydroxyalkylene dihalogen, and glycidyl ethers.

### Claim 27 (depends on 25)

The method as claimed in claim 25, wherein the crosslinking agent is a diepoxide compound.

### Claim 28 (depends on 22)

The method as claimed in claim 22, wherein the crosslinking is carried out in an aqueous medium, an organic solvent, or a mixture of water and an organic solvent.

### Claim 29 (depends on 22)

The method as claimed in claim 22, wherein the crosslinking is carried out in the presence of a crosslinking catalyst.

### Claim 30 (depends on 28)

The method as claimed in claim 28, wherein the crosslinking is carried out at a temperature in the range from about 4° C up to a boiling point of the crosslinking medium.

### Claim 31 (depends on 22)

The method as claimed in claim 22, wherein the crosslinking is carried out in a period in the range from about 10 minutes to about 100 hours.

### Claim 32 (depends on 22)

The method as claimed in claim 22, wherein functional groups become bonded to the membrane.

### Claim 33 (depends on 32)

The method as claimed in claim 32, wherein the functional groups are introduced during or after crosslinking of the hydrolyzed membrane.

### Claim 34 (depends on 33)

The method as claimed in claim 33, wherein the membrane is dried after introducing the functional groups.

### Claim 35 (depends on 32)

The method as claimed in claim 32, wherein the functional groups are ligands which enter into interactions with adsorbates present in fluids.

### Claim 36 (depends on 34)

The method as claimed in claim 34, wherein the membrane is dried from a medium which comprises a pore-stabilizing compound.

### Claim 37 (depends on 1)

An apparatus for membrane chromatography, comprising at least one crosslinked cellulose hydrate membrane as claimed in claim 1.

### Claim 38 (depends on 22)

The method as claimed in claim 22, wherein method further comprises: prior to the hydrolysis, optionally pretreating the cellulose ester membrane in a medium at a temperature in the range from about 20° C to about 100° C.