DE4336301A1 - Electrically conductive hydrogel compsn. - Google Patents

Abstract

Electrically conductive hydrogel compsn. comprises (a) 100 pts. wt. of ethylenically unsatd. stabilised acrylate monomers with a relative molecular wt. of 72-320; (b) 275-600 pts. wt. of an aq. polyol-contg. fluid, comprising deionised water in which a polyol is dissolved (with the ratio being 1:1.5-3); (c) 0.1-8 pts. wt. of a UV initiator; (d) 12-125 pts. wt. of a sec. or tert. amine as a coinitiator; (e) 2.5-12.5 pts. wt. of a polyunsatd. cpd. as crosslinker; (f) 0.2-10 pts. wt. of polyacrylic acid with a relative molecular wt. of 150000-350000; and (g) 0.2-20 pts. wt. of an alkali(ne earth) metal halide which increases the electrical conductivity.

Description

The invention relates to an electrically conductive hydrogel composition and a Process for the preparation of a hydrogel.

Hydrogels or hydrogel bodies are used in particular as a skin-contacting guide body used in electromedicine, eg. B. in electrodes to bioelectrical signals from the Skin of a mammal to external devices or external electrical signals for stimulation biological processes to the skin of a mammal.

The hydrogel forms the ionic conductive layer between the skin and a conductor 1st order like metal plates, with special conductive coatings, metal coatings or through certain admixtures made conductive plastic bodies, often with a silver / silver chloride Combination provided surfaces. The hydrogel needs to be able be, over a prescribed period of application, lasting between a few minutes may extend up to several days to ensure stable transmission of the signals such as In the AAMI standard (Standard for Pregelled ECG Disposable Electrodes, Association for the Advancement of Medical Instrumentation, February 1984 Received) established.

Electrically conductive hydrogels based on unsaturated, free-radical-forming monomers, which are dissolved in a polyol-containing liquid and with the addition of crosslinker, Co-initiator and optionally further additives are polymerized, are already known.

From US-PS 4,539,996 hydrogel compositions consisting of Triethylene glycol bis-methacrylate, benzil dimethyl ketal, acrylic acid, glycerol, water and Potash, known. The difficult-to-control polymerization reaction of this composition is only under inert gas, z. As nitrogen, possible. A polymerization under inert gas however, it is not suitable for continuous strip production.

U.S. Patent No. 4,554,924 discloses a hydrogel composition of a similar type. Powdered polyacrylic acid with sodium salt is immersed in warm distilled water dissolved for one hour and there are potassium chloride, distilled water, acrylic acid, Glycerol, triethylene glycol bis-methacrylate and benzil dimethyl ketal added. The Reaction components are mixed for 4 hours. The exposed electrodes  need to store for about a day at high humidity to have adequate water potential build up in the gel body. The complex preparation of the reaction mixture, the exposure under inert gas and the subsequent wet storage of the polymerized Gel bodies mean a disproportionately high production cost. Also known is a hydrogel composition consisting of 15 to 20 wt .-% acrylic acid and 2 to 4% by weight of polyacrylic acid. As a photoinitiator, this composition contains 1% by weight of benzyldimethylketal. The electrolytic plasticizing system consists of 5 to 40% by weight of water, 20 to 60% by weight of glycerol and 25 to 5% by weight of potassium chloride (U.S. Patent 4,694,835 and U.S. Patent 4,795,516).

In addition to the already o. G. Disadvantages in the polymerization, these compositions as well as those of US Pat. No. 4,539,996 and US Pat. No. 4,554,924 only insufficient Adhesive effect, especially at elevated water content, as it is due can adjust the skin application.

In order to improve this, US Pat. No. 4,848,353 discloses a hydrogel composition, consisting of 5 to 43.5% by weight of acrylic acid, 7 to 45% by weight of N-vinylpyrrolidone, 0.05 to 0.3 wt .-% of triethylene glycol bis-methacrylate, 0.02 to 0.1 wt .-% benzil dimethyl ketal, 5 bis 60% by weight of water, 0.5 to 12% by weight of potassium chloride and 30 to 70% by weight of glycerol are proposed, wherein the acrylic acid is partially neutralized with NaOH. The preparation of the hydrogel takes place by copolymerization by means of UV light and under nitrogen as inert gas. The disadvantage is the relatively long exposure time of 4 minutes and the need the implementation of the copolymerization under nitrogen. There are also large sensor areas The electrode of about 6 cm² required to the desired electrical characteristics to reach.

To be used as an electrode material hydrogel a variety of requirements posed.

The hydrogel must be tolerated by the skin during the period of application and independently of skin absorption a permanent adhesion to the skin and for signal transmission ensure a stable bond to the arrester 1st order. (Adhesive are shaped bodies, which stick to the skin after external mechanical pressure). Another condition is the ability of the gel body, the adhesive tendency under the practical conditions Skin contact for a common application time, if possible also moreover, to maintain it in a useful way. It is necessary to do this Dehydration or excessive swelling, the formation of antiadhesive release layers and to avoid microbial degradation phenomena. In addition, the adhesive effect may not by usual corneal rejections as well as sweat and fat deposits  be affected without an abrasive skin preparation. Finally, the Cohesive forces of the gel body be so great that this during application until including does not disintegrate to decrease or significant residues on the skin leaves. The adhesion to the skin must be adjustable to a certain extent In addition to the above requirements also application-specific features account; so the adhesion should not be so great that when removing a gel body Pain or even skin damage may occur as well as possible the hairs on any normal skin may remain there; to take into account is that children, especially newborns, a much more sensitive skin than Adults have old people, however, a dry, wrinkled skin and that at certain Diseases the skin is damaged. Will the gel body, what to his Main application is expected, on or in a corresponding carrier body polymerized in situ, so an adhesion to the carrier body must be feasible, the larger is as the skin to the application, so that the electrode containing the gel, as a functional unit preserved. The cohesion must allow the gel movements that transmitted through the skin, can record as long as possible without, for example thereby accelerated to replace. What was evident so far in the assessment of Quality of adhesion (track) or cohesion was neglected (see U.S. Patent 4,554,924, US Pat. No. 4,777,954, US Pat. No. 4,848,353), the simultaneous consideration of the elastic, in exceptional cases also plastic or mixed, deformation capacity of the gel body. To achieve a permanent mechanical connection is not just the ability to absorb forces, but also the ability to absorb powers Deformation to distribute, throughout the application period. As not The requirement for a transparent gel body, which is to be evaluated negligibly, is negligible allowed, for. B. Skin reactions that can occur on contact of any medium with the skin or disease-related, to be able to observe.

The gel is said to have these numerous properties naturally under reasonable storage conditions with minimal packaging for a long period of time, possibly over a few years, keep. Sterile conditions presuppose numerous quality losses conceivable, such as drying, crystallization, hardening z. B. by postpolymerization, Discoloration, cold flow, etc.

It should also be noted that of the additives or reaction products used no toxic effects may result from skin contact (see DE-PS 40 20 780; "Plastics in food transport", recommendations of the Federal Health Office, C. Heymanns Verlag KG, 1991).  

In addition to these application requirements for the hydrogel this should be in its composition and production cause only a small cost. It is also essential that the composition of the hydrogel enables a mechanized or automated manufacturing process, which in mass production of the electrodes to be produced can be incorporated without problems can.

In order to meet the latter requirement, only such compositions are suitable, the one bulk polymerization of an easily metered liquid reaction mixture allow the polymerization under normal conditions feasible have to be. The already mentioned compositions based on water-soluble Acrylic acid monomers require a reaction under inert gas. also the massive irrational effect of acrylic acid requires a high degree of conversion, so that no disturbing monomer residues occur more.

The invention was based on the object, an electrically conductive hydrogel composition based on water-soluble monomers based on acrylic acid, the meets the required performance characteristics of the hydrogel, caused only a small cost and their processing into a hydrogel in a cost-effective Mass production of the electrodes can be integrated.

According to the invention, the object is achieved by the following hydrogel composition:

• a) 100 parts by weight of ethylenically unsaturated stabilized monomers Acrylic acid base having a molecular weight of 72 to 320,
• b) 275 to 600 parts by weight of an aqueous-polyol-containing liquid deionized Water and a polyol dissolved therein in the ratio 1: 1.5 to 1: 3;
• c) 0.1 to 8 parts by weight of UV initiator,
• d) 12 to 125 parts by weight of a secondary or tertiary amine as coinitiator,
• e) 2.5 to 12.5 parts by weight of a polyunsaturated compound as crosslinker,
• f) 0.2 to 10 parts by weight of polyacrylic acid having a molecular weight of 150,000 up to 350,000 and
• g) 0.2 to 20 parts by weight of a halogen salt of alkali or alkaline earth metals Reinforcement of electrical conductivity.

Components a) to g) form a pourable, storage-stable, liquid at room temperature Reaction mixture which is polymerizable in situ under UV light UV light in situ.

The composition of the invention enables a problem-free, manageable Reaction without the use of inert gas. This makes it possible to bulk polymerization using UV light under normal conditions. The exposure times amount to less than 1.5 min.

The recipe ingredients are inexpensive commercial products.

Further embodiment variants of the invention are, for example, the following.

The acrylic acid or its derivatives and optionally the crosslinker are in an amount from 0.01 to 0.1 parts by weight stabilized with hydroquinone methyl ester. As a polyol is Glycerin used. As a UV initiator known per se product Irgacure 184 of Fa. Ciba Geigy, preferably used in an amount of 0.5 to 5 parts by mass. When Co-initiator as the amine is especially triethanolamine in an amount of 45 to 75 parts by weight suitable. The proportion of the crosslinker, preferably triethylene glycol dimethacrylate, is 4.5 to 6.5 parts by mass. The proportion of polyacrylic acid is preferably at 2 to 5 parts by weight. As the halogen salt is preferably potassium chloride in an amount used from 5 to 12 parts by weight. Furthermore, the composition may contain additives, such as viscosity regulators, odor carriers, inhibitors, electrolytes, bacteriostats, Indicators, colorants, complexing agents, buffers or compatibilizers in one Total amount up to 35 parts by mass.

According to the proposed method for producing a hydrogel of the specified Compositions are the digested components in a light and gas-tight closed container with intensive stirring at a melt temperature below 35 ° C to a liquid reaction mixture, which immediately before Place on a prepared base or the like shed and then under Influence of UV radiation, without exclusion of air depending on the layer thickness within a Polymerization time of 20 to 250 seconds.

The predominantly used range of the spectrum of the UV rays lies between 180 to 350 nm. The preparation can be either in a continuous or discontinuous Process be performed. The polymerization takes place directly at the site a suitable carrier where the hydrogel remains until final use. It is also possible the reaction mixture after its preparation without modification  their reaction properties for at least 24 hours store in a light-tight container at room temperature. In the hydrogel and textile inserts can be introduced. It is also possible, the hydrogel on one side with a pressure-sensitive adhesive coated and on the other Side with an anti-adhesive area-like structure.

The hydrogel is characterized by excellent performance properties out. It is transparent, highly elastic, hypoallergenic and adhesive. The gel body with his adhesive surface is homogeneous in itself. The gel has a very good skin compatibility and ensures a permanent fit on the skin surface. His adhesion is neither due to normal movements nor through the skin Sweat or fat secretions impaired. The cohesive forces of the gel body are sufficiently large to be fully functional over the intended application time to ensure. After losing weight of the skin he leaves no Residues on the skin. Despite the good adhesive strength occur in the removal of the gel body from the skin no pain or skin damage. According to the Formulation compositions for the hydrogel allow for different settings achieve the adhesion effect, so that different variants for different Skin types can be offered. The gel body has an excellent Deformation behavior, in particular, he is able to force through deformation during the entire application period. Due to the transparency of the gel body can z. B. occurring skin reactions are observed.

An essential advantage of the hydrogel composition according to the invention consists in the simple and inexpensive production of the hydrogel. The production of the Hydrogels can easily enter an automated electrode production with high output be involved. This makes it possible to significantly increase the operating costs reduce.

The invention will be described below in some examples for the production of electrodes and their application will be explained in more detail.

Example 1

In an electronically controlled device operating in uniform steps Transport unit is prepared an electrode body, which has one for the gel body  provided cavity has and has the following structure. The electrode is assembled made of a skin-compatible pressure-sensitive adhesive coated flexible carrier layer - For example, a PE film with a material thickness of 150 microns, as required by the company Medifix (GB) - with a ring attached to the adhesive side of 2 mm height and 18 or 22 mm diameter PE foam (Vito Irmen), in whose Center one mechanically and electrically through each other through the carrier layer connected unit of Eyelet (Ag / AgCl outer surface, Micron Medical Products, USA) and Stud (stainless steel, Nordtool, Denmark) largely free of their own potential Derive the body signals to the external connections. In through the carrier layer and foam ring formed cavity, in whose base the eyelet sits, is by means of a metering device on the step movement of the transport device rheological set reaction solution filled, which has the following composition and with light completion previously in a stainless steel vessel with about twice the volume of the volume to be recorded was prepared with intimate mixing (data in parts by weight):

100 Acrylic acid stabilized with 0.05 part by weight of hydroquinone methyl ether (pure) 3.5 Photoinitiator; Irgacure 184 (Ciba Geigy) 250 Glycerol (86%) 130 deionized water 6.0 Potassium chloride (pure) 59 co-initiator; Triethanolamine (pure) 5.3 crosslinking agents; Triethylene glycol dimethacrylate (pure) 3.0 Polyacrylic acid (Goodrite K702, 25% in water, Mr = 240,000) 10 Viscosity regulators; Amylopectin (open-minded) 2.0 Odor carrier; eucalyptol

In the subsequent UV exposure section, equipped with UV400H lamps from the company. Hönle, the reaction mixture is polymerized for a period of 80 seconds. After leaving the UV route, the sticky top of the track becomes siliconized Plastic sheet (eg Perlasic-LF, Fa Papierfabrik Perlen, Switzerland) covered and the Electrodes cut out by means of a punch so (diameter 55 mm) that the gel body sits centrally.

After the usual test procedure (measurement at the electrode pair "face to face", cf.  U.S. Patent No. 4,848,353) have required electrical characteristics for ECG electrodes determined:

400 DC resistance in ohms (after 30 s, <100 μA, 10 Hz) 430 as above, after defibrillation simulation 220V 0.3 DC self-potential in mV (after 60 s stabilization) 8.8 DC residual potential in mV, 5 s after defibrillation simulation 0.0 DC potential decay rate in mV / s, 30. , , 35 s after defibrillation simulation

The practical suitability was determined below:
The ECG electrode was worn for 24 hours by 10 subjects subject to normal loading, with no detachment or skin irritation. After removing the electrode, the gel body was still sticky. Visible residues on the skin in the outer periphery of the substrate were easy to remove with benzine. Immediately after application of the electrodes to untreated skin and after 24 hours wearing time undisturbed ECG curves were removable. The electrodes are transparent except for the areas covered by foam ring and Stud / Eyelet.

example 2

Analogously to Example 1, the stepwise device with transport unit a transparent polymer web made of PE with a one-sided hypoallergenic pressure-sensitive adhesive coating fed. However, this time the cavity for receiving the gel body by thermal deformation with a depth of 2.5 mm and a diameter formed by 18 mm.

In this cavity, a reaction solution is metered, which has the following composition and worked up as in Example 1 (in parts by mass):

100 Acrylic acid stabilized with 0.05 part by weight of hydroquinone methyl ether 300 Glycerol (86%) 150 deionized water 5.0 potassium chloride 3.5 Photoinitiator Darocur 1173 (Ciba Geigy) 58.8 Co-initiator, triethanolamine 5.3 crosslinking agents; triethyleneglycol 3.0 Polyacrylic acid (Goodrite K 702, 25% in water, Mr = 240,000) 9.5 Viscosity regulators; Amylopectin (open-minded)

As in Example 1, the reaction mixture is polymerized for a period of about 70 seconds, then covered the top of the track. The electrodes are cut out.

As electrical parameters were measured:

380 DC resistance in ohms (after 30 s, <100 μA, 10 Hz) 385 as above, after defibrillation simulation 220V 0.3 DC self-potential in mV (after 60 s stabilization) 6.8 DC residual potential in mV, 5 s after defibrillation simulation 0.0 DC potential decay rate in mV / s, 30. , , 35 s after defibrillation simulation

The practical suitability was determined below:
The electrode was worn for 3 days by 10 subjects subject to normal stress, with 3 persons suffering partial detachment from the edge of the film, slight skin irritation outside the gel area was experienced by 5 persons. After removal of the electrode, the gel body was re-attachable. Visible residues on the skin were only in the outer edge of the film, which were easy to remove with benzine.

The electrode maintained its good transparency.

Immediately after placing the electrodes on untreated skin and after 72 hours wearing time undisturbed ECG curves were removable.

Application trials with the long-term ECG and the ergometry were positive. In observed tests on subjects with known sensitization to covers with acrylic resin pressure sensitive adhesives could begin after about 6 hours Skin redness to be traced in the outer edge region, so that by replacing the electrodes serious skin irritation were avoided.  

example 3

Analogously to Example 1, the device operating in steps becomes a flexible polymer web made of polyethylene of 120 microns thickness. First, in the increment of the Transport device punched a breakthrough of 3 mm in diameter, over the later the lead-off sensor is set. Now the siliconized between the cuts is Covering paper pulled off evenly upwards. A stud (eg made of stainless steel, Fa. Nordtool, Denmark) forms, fed from below, the later external contact of the electrode; an eyelet (eg made of fiber-filled ABS, coated with an Ag / AgCl layer, Fa. Micron Medical Products; USA) as a sensor contact with the gel body. Stud and eyelet be by means of a feed and sink unit through the introduced breakthrough intimately interconnected.

On the pressure-sensitive adhesive coated surface of the PE film as a textile nonwoven web based on of viscose fibers (Norafin, 25 g / m², Verband- und Vliesstoffe Wiesenbad GmbH) unrolled and rolled up. On this web, the Leitgel forming reaction mixture is distributed. The reaction mixture is rheologically adjusted so that the required layer thickness of the gel body of about 1.3 mm and has the following composition (In parts by mass):

100 Acrylic acid stabilized with 0.05 part by weight of hydroquinone methyl ether 300 Glycerol (86%) 150 deionized water 5.0 potassium chloride 3.5 Photoinitiator Darocur 1173 (Ciba Geigy) 63 triethanolamine 5.0 triethyleneglycol 3.0 Polyacrylic acid (Goodrite K 702, 25% in water, Mr = 240,000) 10.5 Amylopectin (open-minded)

In the following UV exposure section (see Example 1), the reaction mixture exposed and polymerized for a period of about 95 seconds. After leaving the UV The sticky gel surface is spread with a siliconized plastic sheet (eg. Perlasic-LF; Fa. Papierfabrik Perlen, Switzerland). By means of a knife cut are the outside of the sensor transparent electrode body (30 mm diameter) cut out to the siliconized plastic sheet and the remainder removed.  

The siliconized web with the electrodes adhering to it is assembled as required.

Analogously to Example 1, the following electrical characteristics were measured:

345 DC resistance in ohms (after 30 s, <100 μA, 10 Hz) 355 as above, after defibrillation simulation 220V 0.3 DC self-potential in mV (after 60 s stabilization) 6.5 DC residual potential in mV, 5 s after defibrillation simulation 0.0 DC potential decay rate in mV / s, 30. , , 35 s after defibrillation simulation

The practical suitability was determined below:
The electrode was worn for 7 days by 10 subjects subject to normal loading, although in 3 persons intensive exertion led to interim detachments, which, however, were not considered to be detrimental as the electrodes could be re-attached. In a person known to be sensitive, there was a faint reddening of the skin under the gel, which could be observed because of the transparency of the electrode. After removal of the electrode, the gel body was re-attachable. Visible residues on the skin did not exist. The wearing properties were rated as very pleasant because the electrode was hardly distracting.

Immediately after placing the electrodes on untreated skin and after 72 hours wearing time were perfect ECG curves removable.

Application trials with the long-term ECG and the ergometry were positive. Corresponding Positive results were obtained on 5- to 10-year-old children during a gestation period 48 hours and on newborns with first orientation experiments over 8 hours determined.

Claims (27)

1. An electrically conductive hydrogel composition based on water-soluble monomers based on acrylic acid, a water-soluble polyol-containing liquid, crosslinker, initiator and optionally further additives, characterized in that these

• a) 100 parts by weight of ethylenically unsaturated, stabilized acrylic acid-based monomers having a molecular weight of 72 to 320,
• b) 275 to 600 parts by weight of an aqueous polyol-containing liquid of deionized water and a polyol dissolved therein in the ratio 1: 1.5 to 1: 3,
• c) 0.1 to 8 parts by weight of UV initiator,
• d) 12 to 125 parts by weight of a secondary or tertiary amine as coinitiator,
• e) 2.5 to 12.5 parts by weight of a polyunsaturated compound as crosslinker,
• f) 0.2 to 10 parts by weight of polyacrylic acid having a molecular weight of 150,000 to 350,000 and
• g) 0.2 to 20 parts by weight of a halogen salt of alkali or alkaline earth metals to enhance the electrical conductivity.

consists. 2. Hydrogel composition according to claim 1, characterized in that the components a) to g) a pourable, liquid at room temperature, storage-stable reaction mixture form under normal conditions by UV light in situ polymerizable is. 3. Hydrogel composition according to claims 1 or 2, characterized that component a) with hydroquinone methyl ether in an amount of 0.01 to 0.1 Mass parts is stabilized. 4. hydrogel composition according to one of claims 1 to 3, characterized that the component e) with hydroquinone methyl ether in an amount of 0.01 to 0.1 mass parts is stabilized.   5. Hydrogel composition according to one of claims 1 to 4, characterized that the polyol is glycerol. 6. hydrogel composition according to one of claims 1 to 5, characterized that the monomer is acrylic acid. 7. Hydrogel composition according to one of claims 1 to 6, characterized that the proportion of the UV initiator is 0.5 to 5 parts by mass. 8. hydrogel composition according to one of claims 1 to 7, characterized that the proportion of the amine is 45 to 75 parts by mass. Hydrogel composition according to any one of Claims 1 to 8, characterized that the amine is triethanolamine. 10. Hydrogel composition according to one of claims 1 to 9, characterized that the proportion of the crosslinker is 4.5 to 6.5 parts by mass. 11. Hydrogel composition according to one of claims 1 to 10, characterized the crosslinker is triethylene glycol dimethacrylate. 12. Hydrogel composition according to one of claims 1 to 11, characterized the proportion of polyacrylic acid is 2 to 5 parts by mass. 13. hydrogel composition according to one of claims 1 to 12, characterized gekennzeichhet, that the proportion of the halogen salt is 5 to 12 parts by mass. 14. Hydrogel composition according to claim 13, characterized in that the Halogen salt is potassium chloride. 15. A hydrogel composition according to any one of claims 1 to 14, characterized in that it contains additives in a total amount of up to 35 parts by weight.   16. Hydrogel composition according to claim 15, characterized in that the Additives Viscosity regulators and / or odor formers and / or inhibitors and / or Electrolytes and / or bacteriostats and / or indicators and / or colorants and / or complexing agents and / or buffers and / or compatibilizers. 17. A process for the preparation of a hydrogel, characterized in that accordingly the compositions specified in claims 1 to 16 the digested Components in a light and gas tight closed container below vigorous stirring at a melt temperature below 35 ° C to a liquid reaction mixture be united, which directly on the spot on a prepared Coated underlay or the like and then exposed to UV radiation polymerized for up to 250 seconds. 18. The method according to claim 17, characterized in that the UV radiation for initiation the polymerization has a major emission in the range of 180 to 350 nm. 19. The method according to any one of claims 17 or 18, characterized in that this continuous or discontinuous. 20. The method according to any one of claims 17 to 19, characterized in that the Polymerization takes place directly in the place of a suitable support, where the Hydrogel remains until final use. 21. The method according to any one of claims 17 to 20, characterized gekennzeichnedt that the Reaction mixture after its preparation without changing their reaction engineering Properties at least over a period of 24 hours in a light-tight sealed container is stored at room temperature. 22. The method according to any one of claims 17 to 21, characterized in that in the Hydrogel textile inserts are introduced. 23. The method according to any one of claims 17 to 22, characterized in that the Hydrogel on one side of a pressure-sensitive adhesive coated and on the other Page surrounded by an antiadhesive sheetlike structure.   24. Hydrogel prepared according to one of the preceding claims 17 to 23, 25. Hydrogel according to claim 24, characterized in that this transparent, highly elastic, hypoallergenic and adhesive. 26. Use of a hydrogel according to one of the preceding claims 24 or 25, for making an electrically conductive connection between the skin of a Mammal and an external evaluation or stimulation device via an electrical 1st order leader.