Patent Application
20080112984
The present invention relates to hydrogels containing polyvinyl alcohols and/or polyvinyl alcohol copolymers, to methods for producing the hydrogels, and to the use of the hydrogels as materials in the biomedical and pharmaceutical field, for producing contact lenses, for the controlled release of active substances, as a carrier material for inclusion-immobilized biocatalysts, as a carrier material for transition metal catalysts, as a material for producing reactive membranes, as an additive to drilling fluids, as a displacing agent in oil recovery, as an additive for cement and as an additive to highly viscous fluids such as crude oil to improve the flowability and increase the speed of conveyance, and as a component of cosmetic products.
Hydrogels are water-containing gels based on hydrophilic polymers, which are present in the form of three-dimensional networks. As hydrogels, these polymers are insoluble in water but swell up to an equilibrium volume while largely retaining their shape. The network formation takes place predominantly via chemical bonding of the individual polymer chains, but is also possible in a physical manner by means of electrostatic, hydrophobic or dipole/dipole interactions between individual segments of the polymer chains. By selecting the monomers used to build the polymers, the type of crosslinking and the crosslinking density, it is possible to set desired properties of the hydrogels in a targeted manner. The necessary hydrophilicity of the polymers is provided inter alia by hydroxyl, carboxylate, sulphonate or amide groups. Synthetic hydrogels are based inter alia on poly(meth)-acrylic acids, poly(meth)acrylates, polyvinylpyrrolidone or polyvinyl alcohol. Hydrogels are in general very compatible with living tissues (source: Römpp Lexikon Chemie—Version 2.0, Stuttgart/New York: Georg Thieme Verlag 1999).
Hydrogels based on polyvinyl alcohol are known (cf. US2003008396A1, US2001029399A1, US0006231605B1, US0005981826A, WO2001044307A3, WO1998050017A1, Hassan, Christie M.; Peppas, Nikolaos, A.; Advances in Polymer Science (2000), 153 (Biopolymers, PVA Hydrogels Anionic Polymerisation Nanocomposites), 37-65, Peppas, Nikolaos A., Hydrogels Med. Pharm. (1987), 2, 1-48, and the literature cited therein). Hydrogels based on polyvinyl alcohol can be produced by various methods, for example, by repeated freezing and thawing of an aqueous solution of polyvinyl alcohol, by the action of ionizing radiation (UV light, gamma radiation) on an aqueous solution of polyvinyl alcohol, or by reacting polyvinyl alcohol with crosslinking reagents such as glutaraldehyde, acetaldehyde, formaldehyde, maleic acid, oxalic acid, alginic acid, dimethylurea, glyoxal, hydrochloric acid, polyacrolein, diisocyanates and/or divinyl sulphate.
Hydrogels based on polyvinyl alcohols are usually produced from conventional, linear polyvinyl alcohol. In this case, a turbidity of the hydrogel due to crystalline regions occurs, which means that the hydrogels based on conventional polyvinyl alcohol are only suitable to a limited extent for optical applications, such as contact lenses for example. Moreover, hydrogels based on conventional polyvinyl alcohol are not given their mechanical properties until the hydrogel is crosslinked.
Surprisingly, it has now been found that hydrogels based on polyvinyl alcohols with special geometries, such as star-shaped geometries for example, as described in DE10343607 (Schulte et al./Celanese Ventures GmbH) and DE10356574 (Bruckmann et al./Celanese Ventures GmbH), give rise to a lower degree of microcrystallinity in the hydrogel, which leads to improved optical properties, and have improved mechanical properties. Furthermore, the special geometry of the polyvinyl alcohols, as a result of crosslinking the polymers prior to formation of the hydrogel, leads to reduced attrition.
The present invention therefore relates to hydrogels containing at least one polyvinyl alcohol star polymer.
Within the context of the present invention, hydrogels containing at least one polyvinyl alcohol star polymer are understood to mean both hydrogels in which exclusively one or more polyvinyl alcohol star polymers are used as polymer, and mixtures of polyvinyl alcohol star polymers with other polymers. Particular preference is given here to mixtures of polyvinyl alcohol star polymers with conventional polyvinyl alcohol in a ratio of 99:1 to 1:99. Particular preference is also given to mixtures of polyvinyl alcohol star polymers with polyacrylic acids, polymethacrylic acids, polyacrylates, polymethacrylates and polyvinylpyrrolidone in a ratio of 99:1 to 1:99.
In addition to the aforementioned polyvinyl alcohol star polymers, the hydrogels according to the invention also contain water, as the name suggests.
Polyvinyl alcohols with special geometries can be produced by various methods, on the one hand via a transition-metal-catalyzed production of polyvinyl acetate, as described in DE10238659, followed by saponification, as described in DE10343607, or via a copolymerization of vinyl acetate with crosslinking comonomers, followed by saponification, as described in DE10356574.
Hereinbelow, the polyvinyl alcohols and polyvinyl alcohol copolymers described in DE10343607 and DE10356574 will be referred to as polyvinyl alcohol star polymers.
Polyvinyl alcohol star polymers according to DE10343607 and DE10356574 are understood to mean compounds of the formula I, II or III
in which
Polyvinyl alcohol copolymers based on polyvinyl ester copolymers are obtainable by a method comprising the steps:
in which:
Within the context of the present invention, a C1-C20 carbon-containing group will be understood to mean preferably the radicals C1-C20 alkyl, particularly preferably methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, s-butyl, t-butyl, n-pentyl, s-pentyl, cyclopentyl, n-hexyl, cyclohexyl, n-octyl or cyclooctyl, C1-C20 alkenyl, particularly preferably ethenyl, propenyl, butenyl, pentenyl, cyclopentenyl, hexenyl, cyclohexenyl, octenyl or cyclooctenyl, C1-C20 alkynyl, particularly preferably ethynyl, propynyl, butynyl, pentynyl, hexynyl or octynyl, C6-C20 aryl, particularly preferably phenyl, biphenyl, naphthyl or anthracenyl, C1-C20 fluoroalkyl, particularly preferably trifluoromethyl, pentafluoroethyl or 2,2,2-trifluoroethyl, 06-020 aryl, particularly preferably phenyl, biphenyl, naphthyl, anthracenyl, triphenylenyl, [1,1′;3′,1″]-terphenyl-2′-yl, binaphthyl or phenanthrenyl, C6-C20 fluoroaryl, particularly preferably tetrafluorophenyl or heptafluoronaphthyl, C1-C20 alkoxy, particularly preferably methoxy, ethoxy, n-propoxy, i-propoxy, n-butoxy, i-butoxy, s-butoxy or t-butoxy, C6-C20 aryloxy, particularly preferably phenoxy, naphthoxy, biphenyloxy, anthracenyloxy, phenanthrenyloxy, C7-C20 arylalkyl, particularly preferably o-tolyl, m-tolyl, p-tolyl, 2,6-dimethylphenyl, 2,6-diethylphenyl, 2,6-di-i-propylphenyl, 2,6-di-t-butylphenyl, o-t-butylphenyl, m-t-butylphenyl, p-t-butylphenyl, C7-C20 alkylaryl, particularly preferably benzyl, ethylphenyl, propylphenyl, diphenylmethyl, triphenylmethyl or naphthalenylmethyl, C7-C20 aryloxyalkyl, particularly preferably o-methoxyphenyl, m-phenoxymethyl, p-phenoxymethyl, C12-C20 aryloxyaryl, particularly preferably p-phenoxyphenyl, C5-C20 heteroaryl, particularly preferably 2-pyridyl, 3-pyridyl, 4-pyridyl, quinolinyl, isoquinolinyl, acridinyl, benzoquinolinyl or benzoisoquinolinyl, C4-C20 heterocycloalkyl, particularly preferably furyl, benzofuryl, 2-pyrrolidinyl, 2-indolyl, 3-indolyl, 2,3-dihydroindolyl, C8-C20 arylalkenyl, particularly preferably o-vinylphenyl, m-vinylphenyl, p-vinylphenyl, C8-C20 arylalkynyl, particularly preferably o-ethynylphenyl, m-ethynylphenyl or p-ethynylphenyl, or a C2-C20 heteroatom-containing group, particularly preferably carbonyl, benzoyl, oxybenzoyl, benzoyloxy, acetyl, acetoxy or nitrile, wherein one or more C1-C20 carbon-containing groups may form a cyclic system.
Within the context of the present invention, a bridging C1-C20 carbon-containing group will be understood to mean preferably C1-C20 alkyl, particularly preferably methylene, ethylene, propylene, butylene, pentylene, cyclopentylene, hexylene or cyclohexylene, C1-C20 alkenyl, particularly preferably ethenyl, propenyl, butenyl, pentenyl, cyclopentenyl, hexenyl or cyclohexenyl, C1-C20 alkynyl, particularly preferably ethynyl, propynyl, butynyl, pentynyl or hexynyl, C1-C20 aryl, particularly preferably o-phenylene, m-phenylene or p-phenylene, or a C1-C20 heteroatom-containing group, particularly preferably carbonyl, oxycarbonyl, carbonyloxy, carbamoyl or amido.
The present invention also relates to the production and use of the hydrogels according to the invention.
The hydrogels according to the invention, which contain a polyvinyl alcohol star polymer may be produced for example by:
Further components are understood to mean, inter alia:
Compared to hydrogels based on conventional polymers, the hydrogels according to the invention are characterized by a higher level of clarity (comparison of the haze values: see Examples 3 and 4).
Compared to hydrogels based on conventional polymers, the hydrogels according to the invention are characterized by a higher level of resistance to water, which is advantageous when used as a carrier material for inclusion-immobilized biocatalysts, for example, for wastewater treatment (comparison of the resistance to water: see Examples 7 and 8).
Examples of hydrogels according to the invention, which serve to explain but not limit the invention, include products based on mixtures of:
The invention will be explained by the following examples, which nevertheless do not limit the invention in any way.
167 ml of a 1% methanolic sodium hydroxide solution in a 1000 ml round-bottomed flask are heated to 50° C. in a water bath. A solution of 50 g of polyvinyl acetate star polymer (produced according to DE10238659) in 333 ml of methanol is added dropwise thereto over a period of 30 min. At the end of the addition, stirring is continued for a further 30 min. The white precipitate is filtered off, washed with methanol until non-alkaline, and dried in vacuo. Yield: 25.0 g. 1H-NMR (500 MHz, [D6]-DSMO): δ=6.65 (s, aromatic H), 4.65, 4.46, 3.89, 3.84, 3.31, 1.44-1.33 (4×s, 1×m, PVOH) ppm.
132 ml (1.43 mol) of vinyl acetate, 9.0 g (70.2 mmol) of diallylformal, 1.6 ml (7.3 mmol) of tris-(2,2,2-trifluoroethylphosphite and 1.25 g (3.6 mmol) of dibenzoyiperoxide (70%, remainder: H20) are placed in 68 ml of toluene. The clear, colourless solution is stirred at 70° C. for 20 h. The volatile components are removed in an oil pump vacuum and the polyvinyl acetate star polymer is taken up in 200 ml of methanol. This solution is added dropwise over 15 min to 400 ml of a 1% NaOH solution in methanol. Stirring is continued for a further 90 min at 50° C. The polyvinyl alcohol is filtered off, washed with methanol until neutral, and dried in the oil pump vacuum. Yield: 14.4 g (22%) 1H-NMR (500 MHz, [D6]-DSMO): S=5.92-5.87 (m), 5.24, 5.13 (2×d), 4.66, 4.61, 4.46, 4.22, 4.21, 4.10, 4.09, 4.00, 3.89, 3.84, 3.35, 3.16, 1.43-1.33 (13×m) ppm.
25 g of polyvinyl alcohol star polymer (Example 1) are dissolved in 75 ml of dematerialized water at 70° C. The solution is placed in a flat metal dish (20×20 cm), covered with a lid and stored for 12 h at −30° C. Thereafter, the solution is allowed to come to room temperature over 12 h and the freezing/thawing process is repeated a further two times. The hydrogel is obtained in the form of a film having a thickness of 0.25 cm. Turbidity (haze value in percent): 1.3.
25 g of polyvinyl alcohol (Celvol 103 from Celanese) are dissolved in 75 ml of dematerialized water at 70° C. The solution is placed in a flat metal dish (20×20 cm), covered with a lid and stored for 12 h at −30° C. Thereafter, the solution is allowed to come to room temperature over 12 h and the freezing/thawing process is repeated a further two times. The hydrogel is obtained in the form of a film having a thickness of 0.25 cm. Turbidity (haze value in percent): 4.6.
2 g of polyvinyl alcohol star polymer (Example 2), 2 g of polyvinyl alcohol (Celvol 103 from Celanese), 0.5 g of alginic acid sodium salt and 0.15 g of sodium hydrogen carbonate are dissolved in 50 ml of water at 70° C. and, after cooling to room temperature, are added dropwise to 250 ml of a 0.1 M calcium chloride solution in large droplets from a syringe without a cannula, with slow stirring, whereby spherical particles having a size of approx. 3 mm are formed. The particles are isolated by means of careful filtration through a glass frit, and are added to a 40° C. solution of 5 g of formaldehyde (37% in water), 50 g of concentrated sulphuric acid and 25 g of sodium sulphate. After one hour, the solidified spherical particles are isolated by filtration and washed with water until neutral. Yield: 43 g of hydrogel as spherical particles.
4 g of polyvinyl alcohol (Celvol 103 from Celanese), 0.5 g of alginic acid sodium salt and 0.15 g of sodium hydrogen carbonate are dissolved in 50 ml of water at 70° C. and, after cooling to room temperature, are added dropwise to 250 ml of a 0.1 M calcium chloride solution in large droplets from a syringe without a cannula, with slow stirring, whereby spherical particles having a size of approx. 3 mm are formed. The particles are isolated by means of careful filtration through a glass frit, and are added to a 40° C. solution of 5 g of formaldehyde (37% in water), 50 g of concentrated sulphuric acid and 25 g of sodium sulphate. After one hour, the solidified spherical particles are isolated by filtration and washed with water until neutral. Yield: 37 g of hydrogel as spherical particles.
10 g of hydrogel from Example 5 were placed in a 50 ml one-way syringe, on the bottom of which there is a plastic sieve (mesh width 0.75 mm). The hydrogel was covered with a plastic sieve and the hollow space above the hydrogel was filled with glass wool. The syringe was closed with a rubber stopper, through which a 1 mm Teflon hose passed. Using a pump, tap water was passed through the Teflon hose at a flow rate of 1 ml/min over the hydrogel, over a period of one week. Thereafter, the hydrogel was removed from the syringe and weighed. After one week, 9.2 g of hydrogel from Example 5 were isolated.
10 g of hydrogel from Example 6 were placed in a 50 ml one-way syringe, on the bottom of which there is a plastic sieve (mesh width 0.75 mm). The hydrogel was covered with a plastic sieve and the hollow space above the hydrogel was filled with glass wool. The syringe was closed with a rubber stopper, through which a 1 mm Teflon hose passed. Using a pump, tap water was passed through the Teflon hose at a flow rate of 1 ml/min over the hydrogel, over a period of one week. Thereafter, the hydrogel was removed from the syringe and weighed. After one week, 8.1 g of hydrogel from Example 6 were isolated.
| Number | Date | Country | Kind |
|---|---|---|---|
| 10 2004 019 504.8 | Apr 2004 | DE | national |
| Filing Document | Filing Date | Country | Kind | 371c Date |
|---|---|---|---|---|
| PCT/EP05/04348 | 4/22/2005 | WO | 00 | 8/17/2007 |
