Hydrogel, Production, And Medical Device Comprising An Electrode Coated Therewith

Abstract

The invention relates to a hydrogel comprising cross-linked copolymer chains, wherein some of the repetitive units of the copolymer are based on functionalized monomers that contain both a polymerizable group and a complexing group, wherein the functionalized monomers further contain a cationic group, and wherein the hydrogel comprises anions corresponding to said cationic groups.

Claims

1. A hydrogel comprising cross-linked copolymer chains, with some of the repetitive units of the copolymer being based on functionalized monomers that have both a polymerizable group and a complexing group, characterized in that the functionalized monomers furthermore have a cationic group; and in that that the hydrogel comprises anions corresponding to these cationic groups.

2. A hydrogel in accordance with claim 1, characterized in that the cationic group is a quaternary nitrogen atom.

3. A hydrogel in accordance with claim 1, characterized in that the polymerizable group comprises a polymerizable ethylenic functionality.

4. A hydrogel in accordance with claim 1, characterized in that the complexing group is a thiol, a phosphonic acid ester, an alkyne, a 1,3-dicarbonyl, an enamine, a dithiol, a triazole, a tetrazole, a carboxylic acid hydride, a cyanide, a chelate-forming amine, a diamine or a polyamine.

5. A hydrogel in accordance with claim 1, characterized in that at least some of the anions are chloride, iodide, bromide, aryl sulfonate, alkyl sulfate, sulfate, aryl phosphonate, alkyl phosphonate, monoalkyl phosphonate, dialkyl phosphate, hydrogen phosphate, phosphate, hexafluorophosphate, hydrogen carbonate, carbonate, carbamate, alkyl carbonates, triflate or carboxylate.

6. A hydrogel in accordance with claim 1, characterized in that at least some of the anions are complex-forming anions.

7. A hydrogel in accordance with claim 1, characterized in that at least some of the anions are bound to the copolymer chains in a covalent manner.

8. A hydrogel in accordance with claim 1, characterized in that a further portion of the repetitive units of the copolymer is based on additional monomers that have a polymerizable group, but that do not further have both a complexing and a cationic group.

9. A hydrogel in accordance with claim 1, characterized in that the copolymer furthermore comprises cross-linked repetitive units that are based on cross-linkable monomers that have more than one polymerizable group.

10. A hydrogel in accordance with claim 1, characterized in that the hydrogel furthermore includes multivalent alcohols.

11. A hydrogel in accordance with claim 1 characterized in that the portion of the repetitive units based on functionalized monomers in the hydrogel amounts to 0.1 to 40 wt. %; and/or in that the portion of the repetitive units based on additional monomers in the hydrogel amounts to 5 to 50 wt. %; and/or in that the portion of the cross-linked repetitive units in the hydrogel amounts to 0.01 to 5 wt. %; and/or in that the portion of the multivalent alcohols in the hydrogel amounts to 5 to 60 wt. %.

12. A method of manufacturing a hydrogel in accordance with claim 1, characterized in that the cross-linked copolymer chains are manufactured by a radical chain polymerization of the functionalized monomers.

13. A method in accordance with claim 12, characterized in that the polymerization is photoinitiated.

14. A method in accordance with claim 12, characterized in that the method comprises a process of an at least partial replacement of the anions after a completed manufacture of the cross-linked polymer chains.

15. A medical device comprising at least one electrode, characterized in that at least a part of the electrode is coated with a hydrogel in accordance with claim 1.

16. A hydrogel in accordance with claim 1, characterized in that the cationic group is an ammonium group

17. A hydrogel in accordance with claim 1, characterized in that the cationic group is an amine type or an azolium group.

18. A hydrogel in accordance with claim 1, characterized in that the polymerizable group comprises a polymerizable ethylenic functionality that is a substituted or unsubstituted vinyl group, allyl group, (meth)acrylate group or (meth)acrylamide group.

19. A hydrogel in accordance with claim 1, characterized in that at least some of the anions are citrate, malate, ethylenediaminetetraacetate, 2-phospho-L-ascorbate, or imidodiacetate.

20. A hydrogel in accordance with claim 1, characterized in that the copolymer furthermore comprises cross-linked repetitive units that are based on cross-linkable monomers that have exactly two, exactly three, or exactly four polymerizable groups.

Description

[0079] Further details and advantages result from the Figures and embodiments discussed in the following. There are shown in the Figures:

[0080] FIG. 1: a cross-section of an ECG electrode that is coated with a hydrogel in accordance with the invention;

[0081] FIG. 2: a cross-section through a different ECG electrode that is likewise coated with a hydrogel in accordance with the invention;

[0082] FIG. 3: a cross-section through yet another ECG electrode that is likewise coated with a hydrogel in accordance with the invention;

[0083] FIG. 4: views of a defibrillator in accordance with the invention;

[0084] FIG. 5: a cross-section through a further biomedical electrode that is coated with a hydrogel in accordance with the invention; and

[0085] FIG. 6: a crystalline structure of the 3-(prop-2-yn-1-yl)-1vinyl-1H-imidazolium chloride of synthesis example 3.

[0086] The biomedical electrode (ECG electrode with button) shown in FIG. 1 has a carrier, for example from plastic or from a plaster material. This carrier is adhesively coated on its lower side facing the skin. A masking film 2 protects, on the one hand, the adhesive layer on the lower side of the carrier 1 and, on the other hand, the conductive hydrogel 3 in accordance with the invention described below in detail. This masking material 2 is removed and the electrode is bonded on before use.

[0087] A label 1a, preferably consisting of a stiffer plastic film, is applied, for example adhesively bonded, to the upper side of the carrier 1. This label 1a forms a part of the carrier and carries the electrical connector element 4 in the form of a button composed of stainless steel or carbon. This connector element is in electrically conductive contact with an electrical lead element 5, wherein the carrier part or the label 1a is arranged at the points 1a between the electrical lead element 5 and the electrical connector element 4 and thus holds the connector button mechanically at the ECG electrode.

[0088] The gel 3 in accordance with the invention can be designed, for example, as a solid gel that is configured in a rigid manner. It can, however, also be present as a thickener in a liquid gel that is held in a sponge.

[0089] The electrical lead element 5 that is electrically conductively connected to the connector element (button 4), is in contact with the conductive gel at itself lower side and is electrically connected to it there.

[0090] The individual parts disposed above one anther are shown spaced apart in FIG. 1. This only serves for a better illustration. In reality, the layers drawn separately above one another are connected to one another, with the protective film 2 being removed before use.

[0091] In the embodiment in accordance with FIG. 2, it is a precabled ECG electrode. The same reference numbers designate the same or similar parts as in FIG. 1. The main difference substantially comprises an electrically conductive cable 6 that is fixedly connected to the electrode being provided instead of the connector button 4, while a cable to an ECG evaluation device, not shown, is connected to the connector button 4. The cable 6 or the strand located therein is electrically connected to the lead element 5 that is in turn in contact with the conductive gel at the lower side. The label 1a at the upper side of the carrier 1 can be configured as electrically conductive and can in so doing establish an electrical contact between the cable 6 and the electrical lead element 5. It is, however, also possible that this carrier part 1a (label) comprises non-conductive material. The cable 6 or the strand located therein then has to be electrically connected to the electrical lead element 5 in another manner.

[0092] The embodiment shown in FIG. 3 is an ECG electrode with a lug contact. The same reference numerals again designate the same or similar parts as in FIGS. 1 and 2.

[0093] A laterally projecting lug 7 that has the carrier material 1, for example a relatively rigid strip of paper of PET, serves as a connector element here. This carrier strip 1 or the lug 7 has an electrically conductive film 5a at the lower side that is connected to a connector terminal. The film 5a can, for example, consist of carbon or can predominantly have this as the electrically conductive component. Suitable such possibilities and alternative possibilities comprise a carbon film and silver lacquer, a carbon film filled with silver, a tin film, or generally a depolarizing film. In the present case, a depolarizing film is to be understood as a film that is able to provide both oxidized species and reduced species simultaneously in combination with a hydrogel. This film 5a is connected to a further film 5b. The film 5b can, for example, comprise an electrically conductive lacquer, that is a different material than the film 5a. It is, however, also possible that the film 5b is completely missing. Ultimately, the two films 5a and 5b together form the electrical lead element that is connected to the conductive gel at the lower side. This lies on the skin after removal of the film 2 and is, in a similar manner to the gel in FIG. 2, also adhesive so that the electrode adheres to the skin.

[0094] The embodiment shown in FIGS. 4a and 4b relates to a defibrillation electrode. The same reference numerals again designate the same or similar parts.

[0095] The design is generally similar to that in the ECG electrodes in FIGS. 1 to 3. The area is lager to enable a current transfer from the defibrillation machine 8 to the human body.

[0096] The conductive gel 3 is preferably a solid gel. An electrical connection from the connector cable 8a via a rivet 9 to the lead element 5 takes place via a film 10.

[0097] In the embodiment shown in FIG. 5, an electrical lead element 5 in the form of a flexible film is provided. Here, a respective three films are printed on the upper side and lower side of the electrical lead element 5, and indeed a dielectric (insulating) film 12 as well as a respective electrically conductive shield film 11 disposed therebetween. It is above all possible with diagnosis electrodes thanks to this shielding to shield interfering electromagnetic radiations and other interference sources. The continuation of the lead element, starting from the region covered by the gel 3, simultaneously provides a shielded feed cable. The imprinting of the shielding is possible by a simple manufacture. A good shield effect can nevertheless be achieved.

[0098] Provision is now made in accordance with the invention that the conductive gel 3 represents one of the gels in accordance with the invention and is at least partially connected to the electrical lead element. The electrical lead element 5 can be passivated as protection against corrosion. The lead element is typically of layer form or film form. It can, however, also be present in fiber form.

[0099] It is also possible that the gel comprises different films, with the gel in accordance with the invention representing one or more films of this design. Another variant is that the gel is admittedly set up of one film, but is in turn made up of different gels, with the gel in accordance with the invention again being able to represent one or more parts of this film. A combination of these variants is also possible.

LIST OF REFERENCE NUMERALS

[0100] 1 carrier [0101] 2 cover film [0102] 3 hydrogel in accordance with the invention [0103] 4 connector element [0104] 5 electrical lead element [0105] 6 connector element [0106] 7 electrical connector element [0107] 8 defibrillator [0108] 9 rivet [0109] 10 film over which an electrical conduction takes place [0110] 11 shield element [0111] 12 dielectric film

[0112] The definition of individual reagents used in the following examples is collected in the following Table 1:

TABLE-US-00001 TABLE 1 NaAMPS 50% Sodium salt of the 2-acrylamido-2- methylproansulfonic acid (50% in H.sub.2O) PVP K 90 Polyvinylpyrrolidone K90 Irgacure 754 Photoinitiator from Ciba Esacure KTO 46 1:1 in EtOH Photoinitiator from Lamberti Tylose YP 300000 Hydroxyethylcellulose Lutensol XL 70 Alkylpolyethylene glycolether from BASF CN 3705 Diacrylate triethanolamine from Sartomer Irgacure 2959 1-[4-(2-hydroxy)-phenyl]-2-hydroxy- 2-methyl-1-propane-1-one Esacure DP 250 Photoinitiator from Lamberti Irgacure 184 1-hydroxy-cyclohexyl-phenyl-ketone Bardac 2270 Didecyldimethylammonium chloride

SYNTHESIS EXAMPLE 1

3-(2,4-dioxopentane-3-yl)-1-vinyl-imidazoliumchloride

[0113] ##STR00003##

[0114] 9.42 g vinylimidazole and a spatula tip of hydroquinone monoethyl ether are dissolved in 20 ml acetone to prepare a first solution. The solution is degassed with argon for 10 minutes. A second solution is prepared by dissolving 13.46 g 3-chloroacetylacetonate in 15 ml acetone. The second solution is slowly dripped into the first solution with external ice cooling. The combined solution is held under the external ice cooling for 2 hours and is subsequently stirred at room temperature for 4 hours. An extraction with water and chloroform subsequently takes place, with the water phase being washed three times with chloroform and the water being extracted at the rotary evaporator. 19.87 g product in the form of a yellow highly viscous liquid is obtained.

SYNTHESIS EXAMPLE 2

3-(4-butyryl-5-oxooctyl)-1-vinylimidazolium Chloride

[0115] ##STR00004##

[0116] 0.47 g of the liquid reactant vinylimidazole are presented in a vessel and 1.18 g diethyl (3-chloropropyl) malonate are added in 7.5 ml methanol. The mixture is stirred at room temperature for 48 hours. The solvent is subsequently extracted and the sample is dried under high vacuum. 93% of the theoretical yield of the product is obtained with the NMR spectra shown in the following: 1H NMR (300 MHz, neat) 7.94, 7.51, 7.17, 5.51, 4.96, 4.30, 3.71, 3.58, 2.16, 1.96, 1.33; 13C NMR (75 MHz, neat) 169.32, 136.86, 130.43, 130.23, 116.18, 100.79, 61.54, 51.42, 44.87, 30.44, 26.46, 14.16.

SYNTHESIS EXAMPLE 3

3-(prop-2-yn-1-yl)-1vinyl-1H-imidazolium Chloride

[0117] ##STR00005##

[0118] 4.70 g vinylimidazole are dissolved in 15 ml toluol. 5.32 g propargyl chloride (70% in toluol) are subsequently added. The reaction solution is heated with backflow for 8 hours, with a white deposit being formed. The deposit is subsequently filtered off and washed with ether. 1.837 g (22% of the theoretical yield) of the product is produced in the form of a white powder having the NMR spectra shown in the following: 1H NMR (300 MHz, DMSO) 9.93, 9.92, 9.92, 8.41, 8.40, 8.39, 8.03, 8.03, 8.02, 7.48, 7.45, 7.43, 7.40, 6.10, 6.10, 6.05, 6.04, 5.45, 5.44, 5.42, 5.41, 5.33, 5.32, 3.94, 3.93, 3.92

[0119] An X-ray crystalline structure of the product is shown in FIG. 6.

SYNTHESIS EXAMPLE 4

3-(2-(diethylamino)ethyl)-1-vinyl-1H-imidazolium Bromide

[0120] ##STR00006##

[0121] 4.7 g vinylimidazole are presented in 40 ml methanol and are washed with argon. 9.00 g 2-bromo-N,N-diethylethylamine is slowly dripped in under external ice cooling and the reaction mixture obtained is stirred at room temperature for 48 hours. The solvent is subsequently removed at the rotary evaporator and the created white crystalline product was washed multiple times with diethyl ether. 11.34 g of the product are obtained.

EMBODIMENTS 1 TO 3 AND COMPARISON EXAMPLE 4

[0122] At least one non-functionalized monomer is presented in water and at least one multivalent alcohol is slowly added. In another vessel, the functionalized monomer, which is an ionic liquid, a cross-linking monomer and a photoinitiator are mixed. Once a homogeneous solution of the second solution has been produced, it is slowly dripped into the parent solution while stirring. After combination of the solutions stirring takes place at 500 revolutions per minute for 20 minutes and the solution is degassed in an ultrasound bath for 15 minutes.

[0123] The polymerizable solution obtained in this manner is applied to a tin antimony film (98:2) with the aid of a film drawing machine. The layer thickness of the film amounts to 4 mm. The polymerizable solution is then hardened using a UV mercury vapor discharge lamp. An almost transparent adhesive hydrogel is produced.

[0124] The ingredients of the polymerizable solutions are collected in Table 2. Electrical measurement values and measurement values of the resulting hydrogels obtained as part of the delamination measurement are collected in Table 3.

TABLE-US-00002 TABLE 2 Type or function AB 1 AB 2 AB 3 Cf. B 4 of the ingredient NaAMPS 50% in water 63.74 20.27 46.31 Monomer Acrylic acid 1.35 15.30 11.32 0.51 Monomer Glycerin 25.86 14.75 31.06 20.38 Multivalent alcohol Sorbitol 70% in water 14.00 Multivalent alcohol Triethanolamine 1.55 3.38 Base Ammonium chloride 1.59 1.46 2.20 Conducting salt Water, demineralized 19.04 33.99 18.49 PVP K90 0.27 Thickener 2-hydroxy-2-methyl-1-phenyl-proan-1-one 0.21 0.20 0.33 0.37 Photoinitiator Irgacure 754 0.12 0.17 0.19 Photoinitiator Ethyleneglycoldimethacrylate 0.16 0.24 0.13 Cross-linker Tylose 30000 YP 0.10 0.17 0.09 Thickener Caustic potash 47% in water 3.68 0.34 0.19 Base 3-acrylamido-N-(2-(diethoxyphosphoryl)ethyl)- 3.08 Functionalized N,N-dimethylpropane-1-aminium chloride monomer Trimethylolpropane triacrylate 0.09 Cross-linker Potassium tartrate tetrahydrate 0.72 Conducting salt Sodium oxalate 0.30 Conducting salt Tin oxalate 0.01 0.01 Conducting salt 3-(2-(diethylamino)ethyl)-1-vinyl-1H- 2.25 5.59 Functionalized imidazolium bromide monomer CN 386 (Monoacrylate triethanolamine 1.01 2.23 0.19 Monomer Sartomer) Irgacure 184 0.36 0.19 Photoinitiator 1-vinylpyrrolidone 2.18 1.12 Monomer 4-hydroxybutylvinyl ether 1.22 Monomer Bardac 2270 0.03 Filler (biocide) Potassium sodium tartrate 0.96 Conducting salt Sodium chloride 2.13 Conducting salt Hydroxyethylacrylamide 3.18 11.20 7.60 Monomer Magnesium acetate tetrahydrate 0.83 Conducting salt

TABLE-US-00003 TABLE 3 Type of measurement value AB 1 AB 2 AB 3 Cf. B 4 Delamination on tin antimony film 2.52 1.55 2.15 1.03 98:2 [N] Large signal impedance [Ohm] 0.33 0.35 0.24 0.2 DCO after 4 seconds [mV] 94.6 6.90 22.9 93.7 DCO after 60 seconds [mV] 44.6 8.00 10.5 30.5

[0125] The impedance values and offset voltages were determined in accordance with IEC 60601-2-4.

[0126] The force required for the delamination of the hydrogel should be sufficiently high to prevent an unwanted peeling of the hydrogel. Values of 1 N or more are to be considered as sufficient with respect to the respective film. Small impedance values are preferred, with all the gels easily satisfying the requirement of the standard IEC 60601-2-4 of less than 3 ohms and all the values in the range of less than 1 ohm can be considered as very good. Small offset voltages are important, for example, for recording an ECG.