EP3898867A1

EP3898867A1 - Adhesive substance for bonding with the skin

Info

Publication number: EP3898867A1
Application number: EP19835370.8A
Authority: EP
Inventors: David Pilz; Lili Yuan; Sara Schröder
Original assignee: Beiersdorf AG; Tesa SE
Current assignee: Beiersdorf AG; Tesa SE
Priority date: 2018-12-18
Filing date: 2019-12-17
Publication date: 2021-10-27
Also published as: DE102018222213A1; WO2020127356A1; CN113366075A

Abstract

The invention aims to provide a highly skin-compatible, well-adherent adhesive substance that can be easily and painlessly removed from the skin and is breathable. This is achieved by an adhesive substance for bonding with the skin, which contains a) at least one copolymer based on a monomer composition comprising - at least one (meth)acrylic acid alkyl ester, - at least one ethylenically unsaturated monomer containing at least one carboxy group, and - at least one photoinitiator; and b) at least one carboxylic acid ester containing at least 10 C atoms. The invention also relates to a dressing for bonding with the skin and to a medical device that can be worn on the skin, both comprising the claimed adhesive substance, and to the use of the claimed adhesive substance for producing bonds with the skin.

Description

Adhesive for sticking to the skin

The invention relates to the technical field of adhesives, in particular adhesives for bonding to the skin, as are often used in plasters or other medical skin patches and increasingly also in sensors and similar products bonded to the skin. Specifically, the invention proposes a specially composed adhesive which is particularly easy to remove from the skin with little pain.

Adhesives find a wide range of uses in the manufacture of products for wound care and for other medical applications. The prerequisite for this is that such adhesives are skin-friendly; e.g. They may only contain very small amounts of residual monomers and should not have any irritating or allergenic potential.

The main task of the adhesives used is to securely bond the product intended for application to the skin and, at the end of the application time, to remove the skin easily and as painlessly as possible. The former property is often regarded as the most important property of a patch or similar product, but is not always achievable. Depending on the fluid absorption capacity of the wound dressing and / or the adhesive, and on the water vapor permeability of the product, perspiration or sweating quite often lead to undesired premature detachment from the skin. An objective criterion for differentiating the breathability of plasters is the determination of the water vapor permeability (MVTR), whereby a certain amount of water, e.g. evaporated over a period of 24 hours and at a temperature of 35 ° C through an area covered with the plaster and quantified by differential weighing.

It is obvious that the two properties "secure adhesion" and "gentle peeling"

(minor trauma) are very difficult to reconcile. Reliable adhesion requires rather high adhesive strengths, gentle peeling rather low adhesive forces. An objective criterion for

Differentiating the effects of plaster removal is, for example, the number of

Corneocytes that are torn from the top layer of skin when a patch is torn off and that can then be determined on the adhesive of the removed patch (P. J. Dykes et al., J. Wound Care 10, 7-10 [2001]). Other criteria used to determine the

Removable properties can be used, the adhesive forces are on

l fissile substrates that function as artificial skin in the test, such as paper, whereby the proportion of fiber tears or residues is determined.

There is no lack of attempts in the prior art to eliminate the disadvantages described.

WO 2004/108175 A1 describes a composition for use on the skin based on silicone, which is initially highly viscous and, after curing, becomes a soft, skin-friendly elastomer which adheres to the skin.

WO 2010/121033 A2 describes a silicone gel system which comprises a porous carrier, a pressure-sensitive adhesive based on an acrylate copolymer and a hardened silicone gel pressure-sensitive adhesive thereon.

US 2005/0287191 A1 relates to a hydrogel / fiber composite which is obtained by impregnating the fibers with a solution of polymerizable monomers and then polymerizing. Disadvantages of such systems are usually the instability in contact with water and the complex processing steps in the coating.

WO 2009/010120 A1 describes an acrylate adhesive which comprises at least one alcohol esterified with optionally substituted acrylic acid, the latter being selected from the group of long-chain aliphatic alcohols, fatty alcohols, wax alcohols, wool wax alcohols and sterols.

EP 1 184 039 A2 relates to an adhesive for use on the skin, which comprises the following constituents: 100 parts by weight of an acrylic copolymer, obtained from a monomer composition, comprising

o a (meth) acrylic acid alkyl ester monomer of 40 to 80% by weight,

an alkoxy group-containing, ethylenically unsaturated monomer at 10 to 60 wt .-%, and o a carboxy group-containing, ethylenically unsaturated monomer at 1 to 10% by weight; and

20 to 120 parts by weight of a carboxylic acid ester which is liquid or pasty at room temperature, the acrylic copolymer having a gel fraction of 30 to 80% by weight.

EP 1 367 109 A1 discloses a pressure sensitive adhesive strip comprising the following: comprising an adhesive layer formed from a resin composition

an acrylic acid ester polymer,

o a carboxylic acid ester with 16 or more carbon atoms which is compatible with it and which is liquid or pasty at ordinary temperatures, and

o a crosslinker; and

a film carrying this adhesive layer, which comprises a polyether urethane resin.

Polymers based on ethylenically unsaturated monomers which contain UV crosslinkers built into the polymer structure are described, for example, in WO 03/033544 A1. In particular, the document discloses a process for the preparation of such polymers, in which free-radically copolymerizable phenone derivatives, which have been prepared by reacting isocyanate-reactive compounds with compounds containing isocyanate groups, are radically polymerized using a mixture of ethylenically unsaturated monomers using a polymerization initiator. The copolymers obtained can be used as pressure-sensitive adhesives, but are not optimized for sticking to the skin and are therefore generally not gently removable.

Similar copolymers that can be used in skin adhesives are the subject of EP 0 246 848 A2. The document describes compositions which contain a crosslinked copolymer which is based on alkyl (meth) acrylates and monoethylenically unsaturated aromatic ketone monomers.

There is a continuing need for well-tolerated products for sticking to the skin. The object of the invention was to provide a skin-friendly, adhesive, light and painless to provide skin-detachable and breathable adhesive and products equipped with it for bonding to the skin.

The invention addresses this problem with a specifically composed adhesive. A first and general object of the invention is an adhesive for bonding to the skin, in particular to human skin, which a) at least one copolymer, which can be attributed to a monomer composition, the

at least one (meth) acrylic acid alkyl ester,

at least one ethylenically unsaturated monomer containing at least one carboxy group, and

comprises at least one photoinitiator; and b) contains at least one carboxylic acid ester containing at least 10 carbon atoms.

As has been shown, such adhesives enable sufficiently stable but also easily removable and, moreover, extremely physiologically compatible bonds on the skin. In addition, a wide range of properties can be set using relatively few and easily accessible starting materials, particularly with regard to the balance of adhesive power and low-pain removability.

The monomer composition on which the copolymer of the adhesive according to the invention is based comprises at least one (meth) acrylic acid alkyl ester. The term “(meth) acrylic acid alkyl ester” includes, in accordance with the customary use of the expert, both alkyl esters of methacrylic acid and those of acrylic acid. The alkyl radicals are preferably unfunctionalized alkyl radicals.

In one embodiment, the monomer composition comprises at least one (meth) acrylic acid alkyl ester A which contains 7 to 12 carbon atoms in the alkyl radical. This (meth) acrylic acid alkyl ester A is preferably selected from the group consisting of Isooctyl acrylate, lauryl acrylate and 2-ethylhexyl acrylate; in particular, this (meth) acrylic acid alkyl ester A is 2-ethylhexyl acrylate.

(Meth) acrylic acid alkyl esters A are preferably present in the monomer composition in a total of 15 to 90% by weight, more preferably in a total of 20 to 75% by weight, in particular in a total of 40 to 73% by weight, in each case based on the total weight the monomer composition.

In a further embodiment, the monomer composition comprises at least one (meth) acrylic acid alkyl ester B which contains 1 to 6 carbon atoms in the alkyl radical. This (meth) acrylic acid alkyl ester B is preferably selected from the group consisting of methyl acrylate, methyl methacrylate, ethyl acrylate, n-butyl acrylate, isobutyl acrylate and cyclohexyl acrylate; more preferably from methyl acrylate and n-butyl acrylate. The monomer composition thus particularly preferably comprises methyl acrylate and / or n-butyl acrylate. In particular, the (meth) acrylic acid alkyl ester B is n-butyl acrylate.

In a specific variant, only a (meth) acrylic acid alkyl ester B is contained in the monomer composition as the (meth) acrylic acid alkyl ester.

(Meth) acrylic acid alkyl esters B are preferably present in the monomer composition in a total of 5 to 75% by weight, more preferably in a total of 15 to 55% by weight, in particular in a total of 30 to 45% by weight, in each case based on the total weight the monomer composition.

In principle, the monomer composition can comprise both one or more (meth) acrylic acid alkyl esters A and one or more (meth) acrylic acid alkyl esters B as well as one or more (meth) acrylic acid alkyl esters A and one or more (meth) acrylic acid alkyl esters B.

In a further embodiment, the monomer composition comprises at least two (meth) acrylic acid alkyl esters.

The monomer composition preferably comprises at least one (meth) acrylic acid alkyl ester B which contains 1 to 6 carbon atoms in the alkyl radical, and at least one (meth) acrylic acid alkyl ester A which contains 7 to 12 carbon atoms in the alkyl radical.

The (meth) acrylic acid alkyl ester B is preferably selected from methyl acrylate and n-butyl acrylate. In particular, the monomer composition comprises methyl acrylate. In one embodiment, the monomer composition comprises methyl acrylate and n-butyl acrylate.

The (meth) acrylic acid alkyl ester A is preferably 2-ethylhexyl acrylate.

Generally preferred is the (meth) acrylic acid alkyl ester selected from the group consisting of methyl acrylate, n-butyl acrylate and 2-ethylhexyl acrylate. In principle, one or more (meth) acrylic acid alkyl esters can be present in the monomer composition.

The ethylenically unsaturated monomer which contains at least one carboxy group (-COOH) is preferably selected from acrylic acid and methacrylic acid. In particular, this monomer is acrylic acid. The ethylenically unsaturated monomer containing at least one carboxy group in the monomer composition on which the copolymer is based is preferably from 1 to 10% by weight, more preferably from 2 to 8% by weight, particularly preferably from 3 to 7% by weight, in particular from 4 to 6 wt .-%, each based on the total weight of the monomer composition.

The monomer composition of the copolymer of the adhesive according to the invention further comprises at least one photoinitiator. The photoinitiator enables the copolymer to crosslink and thus acts as an internal, i.e. crosslinker built into the polymer structure. This internal photoinitiator makes it possible to dispense with the addition of an external crosslinker in the production of the adhesive according to the invention.

If they are not fully implemented, photoinitiators or chemical crosslinkers that are not bound to the polymer chain can remain in the mass and become exposed to the skin when the mass is applied. Since these molecules are small and capable of migration and have a high reactivity in accordance with their intended function, they can damage the skin, especially if they can pass through the cell, and can also cause health problems. Due to the photoinitiator belonging to the monomer base of the copolymer and thus incorporated into the polymer chain, the adhesive according to the invention can be provided free of such mobile, toxicologically questionable molecules.

In order to exclude undesirable effects of formulation components at an early stage, comparative preliminary investigations of the adhesive compositions are carried out using cell cultures, so-called cytotoxicity studies (e.g. according to ISO 10993-5).

The photoinitiator is preferably a UV initiator. The photoinitiator is more preferably an acetophenone, benzophenone or benzoin-functionalized, vinyl monomer, particularly preferably an acetophenone, benzophenone or benzoin-functionalized (meth) acrylic acid ester, in particular a benzophenone-functionalized

(Meth) acrylic acid ester. The photoinitiator is further preferably a Norrish type I or Norrish type II initiator, in particular a Norrish type II initiator. This means that the primary step of the crosslinking reaction is hydrogen abstraction by the photochemically excited carbonyl group, which proceeds with radical formation.

Examples of such acetophenone, benzophenone or benzoin-functionalized, vinyl monomers are benzoin acrylate (2-oxo-1,2-diphenylethyl acrylate) or the products sold under the trade names LoMiCure 450 or Visiomer 6976.

Photoinitiators are preferably contained in the monomer composition on which the copolymer is based in an amount of 0.01-2% by weight, more preferably in an amount of 0.05-1% by weight, in particular in an amount of 0.1-1.5% by weight, based in each case the total weight of the monomer composition. These share ranges enable an optimal balance of absorption, possible penetration depth of the radiation and degree of cross-linking. In terms of process technology, this is expressed in easily practicable web speeds during processing. In the property profile, the adhesive according to the invention is characterized inter alia. also characterized by high achievable layer thicknesses and good shear strengths.

In one embodiment, the copolymer can be attributed to a monomer composition consisting of

- at least one (meth) acrylic acid alkyl ester, - At least one ethylenically unsaturated monomer containing at least one carboxy group, and

- There is at least one photoinitiator.

In particular, the copolymer can be based on a monomer composition consisting of

10 to 20% by weight methyl acrylate

12 to 36% by weight of n-butyl acrylate

40 to 74% by weight of 2-ethylhexyl acrylate

3 to 7 wt .-% acrylic acid and

Recycle 0.01 to 2 wt .-% photoinitiator.

The copolymer preferably has a weight-average molar mass (M _w ) of less than 1,500,000 g / mol, particularly preferably less than 500,000 g / mol, in particular less than 350,000 g / mol. For example, the copolymer has a molecular weight of 200,000 to 250,000 g / mol. The molecular weight is determined according to the invention by gel permeation chromatography using the method described herein.

The adhesive according to the invention can contain one or more copolymers as described above. One or more copolymer (s) as described is or are preferably in the adhesive composition according to the invention to a total of 40 to 90% by weight, more preferably to a total of 50 to 80% by weight, in particular to 60 to 78% by weight, for example, 65 to 75 wt .-%, each based on the total weight of the adhesive.

The adhesive according to the invention also contains at least one carboxylic acid ester which contains at least 10 carbon atoms. Such carboxylic acid esters have proven to be sufficiently inert in terms of an extremely low toxic potential; nevertheless, they lead to softening of the adhesive.

The carboxylic acid ester is preferably selected from the group consisting of ethyl myristate,

Isopropyl myristate, isopropyl palmitate, butyl stearate, isopropyl isostearate, hexyl laurate, cetyl lactate, Myristyllaktat, diethyl phthalate, dioctyl phthalate, octyldodecyl myristate, octyldodecyl oleate, Hexyldecyldimethyloktanoat, cetyl ethylhexanoate, 2-, lsocetyl-2-ethylhexanoate, stearyl 2-ethylhexanoate, dioctyl succinate, Dicaprylsäurepropylenglykol, Dicaprinsäurepropylenglykol, Diisostearinsäurepropylenglykol, glyceryl monocaprylate, glyceryl tricaprylate, glyceryl tri-2-ethylhexanoate, glyceryl trilaurate, Glyceryl triisostearate, glyceryl trioleate,

Cycloalkylcarbonsäureestern, tributyl-O-acetyl citrate, Butyltrihexylcitrat, dibutyl adipate, bis (2-ethylhexyl) adipate, diisononyl adipate, bis (2-ethylhexyl) terephthalate, diethylene glycol dibenzoate, alkyl benzoates, and in particular Ci2-Ci5-alkyl benzoates, epoxidized soybean oil, castor oil and acetylated monoglycerides of fully hydrogenated castor oil (COMGHA), sunflower oil, trioctyl trimellitate and tri (2-ethylhexyl) trimellitate.

The carboxylic acid ester is particularly preferably selected from the group consisting of cycloalkyl carboxylic acid esters, tributyl-O-acetyl citrate, acetylated monoglycerides of fully hydrogenated castor oil (COMGHA), bis (2-ethylhexyl) terephthalate, diisononyl adipate, bis (2-ethylhexyl) adipate, epoxidized soybean oil, Trioctyl trimellitate and tri (2-ethylhexyl) trimellitate. In particular, the carboxylic acid ester is a cycloalkyl carboxylic acid ester, in particular diisononylcyclohexanedicarboxylate (DINCH). The cycloalkyl carboxylic acid esters and especially DINCH are largely unreactive and therefore medically harmless; they are also UV-transparent in the absorption region of the copolymer of the adhesive according to the invention and have a low softening point. In this respect they correspond particularly advantageously with the properties of the copolymer and enable efficient UV crosslinking of the adhesive and its processing at low temperatures.

Carboxylic acid esters containing at least 10 carbon atoms are preferably contained in the adhesive according to the invention in a total of 5 to 60% by weight, more preferably in a total of 10 to 55% by weight, particularly preferably in a total of 15 to 45% by weight , in particular to a total of 20 to 40 wt .-%, each based on the total weight of the adhesive.

As has been shown, the adhesive according to the invention wets the skin, in particular the human skin, extremely well. It develops a high instant adhesive strength, which is close to its final adhesive strength on the skin and does not require a longer application time. This is advantageous because bonds made with the adhesive according to the invention immediately become achieve full resilience and pulling off immediately after application does not differ in terms of the perceived pain from pulling it off later.

The adhesive of the invention may contain other additives in addition to the components listed so far, e.g. Crosslinking agents, UV protection agents, antioxidants, hydrophilizing agents, tackifiers, fillers, pigments, dyes, flame retardants, foaming agents, antistatic reagents, surfactants, breathability improvers, antibacterial reagents (e.g. antibacterial silver) and / or pharmacological agents. The adhesive according to the invention particularly preferably contains at least one breathability improver, in particular a compound which comprises at least one polyethylene glycol sequence.

A “breathability improver” is understood to mean an additive that increases the water vapor permeability of the adhesive compared to an adhesive that is otherwise composed identically.

According to the invention, a “polyethylene glycol sequence” is understood to mean a sequence of two or more oxyethylene units (- (0-CH ₂ -CH ₂ -) _n - with n> 2).

The adhesive according to the invention preferably contains at least one sugar ester. Sugar esters are esters of sugars such as e.g. Sucrose and understood by sugar alcohols with organic or inorganic acids. The adhesive according to the invention particularly preferably contains at least one ester of a sugar alcohol. In particular, the adhesive according to the invention contains at least one sorbitan ester. Sorbitan esters are taken to mean tetravalent alcohols derived from glucitol, in particular from D-glucitol, by intramolecular ring closure, of which one or more OH groups are or are esterified, particularly preferably with a fatty acid, in particular with lauric, oil, palmitic or stearic acid is or are esterified. The sorbitan ester is preferably the 1,4-sorbitan ester. Such sorbitan esters are currently e.g. commercially sold under the trade name "Span".

The sorbitan ester is particularly preferably a polyethoxylated sorbitan ester. These compounds are obtained by linking the free OH group (s) of a sorbitan ester with polyoxyethylene. The chemical structure of the polyethoxylated sorbitan esters can be described in somewhat more concrete terms by the name of and the name of the fatty acid ester

io denotes the total number of ethylene oxide units distributed over the non-esterified OH groups. Accordingly, the adhesive according to the invention particularly preferably contains at least one polyethoxylated sorbitan ester selected from the group consisting of PEG-20 sorbitan monolaurate, PEG-4 sorbitan monolaurate, PEG-20 sorbitan palmitate, PEG-20 sorbitan monostearate, PEG-4 sorbitan monostearate, PEG-20 sorbitan tristearate and PEG-20 Sorbitan monooleate. Such polyethoxylated sorbitan esters are currently sold commercially, for example under the trade name "Tween".

As has been shown, the water vapor permeability of the adhesive according to the invention can be improved by adding one or more sorbitan esters. This has beneficial effects on the breathability of adhesive bonds on the skin.

Compounds comprising at least one polyethylene glycol sequence are preferably contained in the adhesive composition according to the invention in a maximum total of 10% by weight, more preferably in a maximum of 7% by weight and in particular in a maximum of 5% by weight, in each case based on the total weight of the Adhesive. The adhesive composition very particularly preferably contains these compounds in a total of 0.5 to 7% by weight, in particular in a total of 1 to 6% by weight, for example a total of 1.7 to 5% by weight.

In particular, sorbitan esters and very particularly preferably polyethoxylated sorbitan esters are contained in the adhesive composition according to the invention to a maximum of 10% by weight, more preferably to a maximum of 7% by weight and in particular to a maximum of 5% by weight, based in each case on the total weight of the Adhesive. The adhesive composition very particularly preferably contains these compounds in a total of 0.5 to 7% by weight, in particular in a total of 1 to 6% by weight, for example a total of 1.7 to 5% by weight.

The adhesive according to the invention can be produced in conventional ways, for example from dispersion or solution. The components are simply dispersed or dissolved in a solvent. The adhesive is obtained by removing the solvent in a drying step.

As has been shown, the adhesive according to the invention can also be obtained from the melt. The components are melted and mixed in the melt or partly incorporated into the melt of the copolymer. The invention further relates to a method for producing an adhesive according to the invention, the

ll comprises melting at least the copolymer and melt mixing at least the copolymer and the carboxylic acid ester. The process is carried out in particular at low temperatures, preferably at less than 60 ° C., in particular at less than 50 ° C. and very particularly preferably at less than 40 ° C. In particular, this also enables the incorporation of temperature-sensitive substances, for example proteins. The other components of the PSA according to the invention described here can also be incorporated heterogeneously and in particular homogeneously into the melt.

Another object of the invention is a pad for gluing on the skin, in particular on human skin, which has at least one carrier material and

comprises an adhesive according to the invention.

Conditions according to the invention have proven to be well tolerated by the skin and, in particular, to be removable with very little pain. In addition, they enable very permanent adhesions on the skin, which show no or only a very slight loss of adhesive strength even under the influence of moisture on the part of the skin or through external contact with water.

Basically all rigid, flexible and elastic fabrics made of synthetic and natural raw materials are suitable. The carrier material preferably consists of an air and water vapor permeable but water impermeable polymer layer with a thickness of approximately 10 to 200 μm. Preference is given to carrier materials which, after application of the adhesive, can be used in such a way that they meet the requirements for a functional skin patch. Examples include textiles such as woven fabrics, knitted fabrics, scrims or nonwovens, nets, foils, foams and laminates made from the above materials and papers. The carrier material is preferably a film, a woven fabric or a nonwoven, particularly preferably with a thickness of 20 to 200 μm, in particular with a weight per unit area of 20 to 200 g / m ² .

These materials can also be pre- or post-treated. Common pretreatments are plasma or corona treatment and hydrophobizing; Common post-treatments are calendering, tempering, laminating, punching, mounting and sterilizing. In principle, both natural and synthetic carrier materials can be used. The carrier material is preferably selected from the group consisting of cotton, viscose, polypropylene, polyesters, polyamides, PET, PVC, polyethylene, polyurethanes, silicones and polylactic acid. The carrier material is preferably selected from the group consisting of cotton, viscose, polyesters, polyethylene and polyurethanes.

The carrier material is particularly preferably a polyurethane film, a polyethylene film, a polyester fleece, a woven fabric made of viscose, polyester or cotton or a woven fabric made of any mixtures of viscose, polyester and / or cotton.

The adhesive according to the invention can be applied to the backing material by conventional methods. It is usually covered on one side with the carrier material, and the resulting structure is applied as a composite. Depending on the carrier material used, the water vapor permeability, the strength of a wound covering, the padding against pressure and other physical properties of the dressing can be controlled.

In order to ensure simple handling, the overlay according to the invention is preferably covered with a protective layer, for example a siliconized paper or a siliconized film (release liner).

The pad according to the invention can further comprise a substrate for absorbing wound exudate.

The overlay according to the invention can in principle be used as a full-surface self-adhesive or partially self-adhesive skin overlay (English: dressing), in particular as a wound dressing, plaster, hygiene article, cosmetic and / or dermatological pad, patch, tape, bandage, colostomy pouch, fixation bandage, kinesio tape, cataplasma, bandage , Surgical cover or mask. The pad according to the invention is preferably a plaster. In addition, it can also be designed as a less adhesive patch or pad, for example, it being possible for the adhesive strength to be set specifically according to the particular application. The adhesive according to the invention is preferably present in the edition according to the invention as a layer with a layer thickness of up to 120 pm, particularly preferably up to 100 pm, in particular up to 80 pm.

Another object of the invention is a wearable device on the skin, in particular on human skin, which comprises an adhesive according to the invention and a medical system. A “medical system” is understood to mean a sequence of elements which, in their entirety and in their interaction, fulfill a medical function, which can consist, for example, in the delivery of an active ingredient, in the stimulation of certain areas of the body or in the collection of medically relevant data . In this respect, the medical device that can be worn on the skin is preferably a device for dispensing a substance, for stimulating areas of the body or for recording medical data.

The delivery of a drug can in particular be provided transdermally; for example, patients with type 2 diabetes insulin, e.g. in a three-day rhythm.

The stimulation is particularly preferably an electronic stimulation, e.g. electronic muscle stimulation (EMS).

Medical data can in particular be the body temperature, the heart rhythm, the blood pressure, the number of steps or the respiratory rate as well as chemical concentrations such as pH, lactate, glucose or chloride values. The medical system can preferably use this data to derive and output certain information, such as sleep status, stress level or training status.

The structure of the medical system can include, in particular, a protective layer, one or more adhesive intermediate layers, one or more stamped parts, one or more insulating layers, in particular against electromagnetic radiation or interference (EMI shielding), and one or more sensors.

Another object of the invention is the use of an adhesive according to the invention for the production of bonds on the skin, in particular on the human skin. The adhesive according to the invention can be used in particular in a support for gluing to the skin or in a medical device that can be worn on the skin, in each case as set out above.

In addition, the adhesive according to the invention can also be used for the production of labels for medical products or for the production of bonds in medical devices.

Examples

Measurement or test methods

Gel permeation chromatography GPC (measurement method A):

The details of the molecular weights and the polydispersity D in this document relate to the determination by gel permeation chromatography. The determination is carried out on 100 μl of clearly filtered sample (sample concentration 0.5 g / l). Tetrahydrofuran with 0.1% by volume of trifluoroacetic acid is used as the eluent. The measurement is carried out at 25 ° C. A column type PSS-SDV, 10 pm, ID 8.0 mm 50 mm is used as the guard column. A column of the type PSS-SDV, 10 pm linear one (SN2071901) with ID 8.0 mm * 300 mm is used for the separation (columns from the company Polymer Standards Service; detection by means of a differential refractometer PSS-SECurity 1260 RID). The flow rate is 0.5 ml per minute. The calibration is carried out against PMMA standards (polymethyl methacrylate calibration)].

Adhesion (test method B):

B1 - adhesive strength steel:

The adhesive strength was determined at a test climate of 23 ° C +/- 1 ° C temperature and 50% +/- 5% rel. Humidity. The adhesive samples were cut to a width of 20 mm and glued to a steel plate. The steel plate was cleaned and conditioned before the measurement. For this purpose, the plate was first wiped with solvent and then left in the air for 5 minutes so that the solvent could evaporate. The side of the sample facing away from the test surface was then covered with 75 μm thick, etched PET film, which prevented the sample from stretching during the measurement. Then the test sample rolled onto the surface. For this purpose, the adhesive was rolled over back and forth five times with a 4 kg roller at a winding speed of 10 m / min. One minute ("initial") or 3 days after rolling, the plate was pushed into a special holder, which makes it possible to pull off the sample at an angle of 180 ° at different speeds (3/30/300 mm / min). The adhesive strength was measured using a Zwick tensile testing machine at a peel speed of 300 mm / min. The measurement results are given in N / cm and are averaged from three individual measurements. B2 - Bristol paper tack:

Following a method by K. Turton et.al. [K. Turton, T. Lane, D. Parker, M. Delbono, S. Di Palo, “In vitro evaluation of the atraumatic removal of a new hydropolymer dressing with silicone”, Wounds UK Harrogate 2015, Poster 4] became the test method of steel adhesion changed that the adhesive surface steel was completely covered with a paper surface by means of a double-sided adhesive strip, which served as a special test reason. Fiches Bristol paper of the brand Oxford Office (model number 100103795, manufacturer number 100103795) with a basis weight of 200 g / m ^{2 was} used as the test substrate. This paper is characterized by the fact that it has a uniform roughness in the test climate as well as a gap resistance that is correlated with human skin. The test results thus obtained allow conclusions to be drawn about the behavior of the adhesive composition pattern on human skin. In the test, the fracture pattern of the paper surface was also recorded, whereby tearing out of paper fibers (PS paper splitting) can be correlated with corneocyte removal on the skin and in particular with trauma when peeling off.

Micro shear path (MSW, test method C):

In accordance with ASTM D 4498, the procedure is as follows: A 50 μm thick sample of the adhesive is provided on one side with a 50 μm thick aluminum foil for stabilization. A test strip with a width of 10 mm and a length of 50 mm is glued to a clean steel plate in such a way that a gluing area of 130 mm2 results. The bond is created by rolling a 2 kg roll back and forth three times. The steel plate is adjusted in the measuring apparatus so that the test strip is in a vertical position and heated to 30 ° C. The system is heated to 40 ° C. At the start of the measurement, a weight of 25 g is attached to the free end of the test strip using a clamp (6.4 g dead weight), which sheared the sample by gravity; At the same time, a micrometer probe is placed on a short piece of test tape that protrudes over the steel plate, which registers the deflection depending on the measurement time, or the shear path is recorded graphically. The micro shear path S1 (maximum micro shear path) is the shear distance after a weight load of 15 min. After this measurement time, the weight is carefully removed from the sample and relaxation is then observed for a further 15 min. After this relaxation time, the micro shear path S2 (relaxed micro shear path) is determined. The micro shear path quotient E = S2 / S1 (elastic component) is determined from the two measured values. This quotient E is a measure of the elasticity (Resetting force) of the PSA. The difference V = 1-E (viscous portion) is a measure of the inelastic flow properties of the adhesive.

K value (measurement method D):

The K value is a measure of the average molecular size of high polymer substances. The principle of the method is based on the capillary viscometric determination of the relative solution viscosity. For this purpose, the test substance is dissolved in toluene by shaking for 30 minutes, so that a 1% solution is obtained. The run-out time is measured in a Vogel-Ossag viscometer at 25 ° C and from this the relative viscosity of the sample solution is determined in relation to the viscosity of the pure solvent. According to Fikentscher [P. E. Hinkamp, Polymer, 1967, 8, 381] the K value can be read.

UV-Vis spectroscopy (measurement method E):

To determine the optical transmission and absorption, diluted solutions of the samples were measured in the solvent acetonitrile in the wavelength range between 190 nm and 1 100 nm with a resolution of 1 nm and referenced against pure solvent. A UV / VIS Spectrometer Specord 250plus from Analytik Jena was used, the liquid samples being used in UV-transparent cuvettes with a sample layer thickness of 1 cm.

Skin Adhesion Test (Test Method F):

The determination of the safe sticking to the skin as well as the sensation of pain when peeling was carried out in a test climate of 23 ° C +/- 2 ° C temperature and 50% +/- 5% rel. Humidity with a group of 20 test persons, 10 of them male, 10 female, 10 aged 20-40 years and 10 aged 40-60 years.

Standardized patches for the test were made as follows:

First, adhesive samples with a width of 30 mm and a length of 72 mm with rounded corners (curve radius 8 mm) were cut. Right in the middle was a rectangular wound pad made of fleece with a length of 25 mm, a width of 12 mm and glued to a thickness of 1 mm. The patches were stuck to the inside of the test person's forearm and lightly pressed three times by hand. A minimum distance of 3 cm to the elbow or wrist was observed. The forearm was washed thoroughly with soap beforehand, then rinsed thoroughly with clear water and dried.

The patches were then worn for 6 hours during light physical activity (PAL factor between 1, 4 and 1, 7).

After the wearing period, the patch was checked and evaluated for edge lifting (yes / no)

The plaster was then removed by hand (according to the test person's habits in using plaster) and the individual sensation with regard to

Trauma (T) on a scale of 1-5 with

1 = no trauma / pain 2 = rather no trauma / pain

3 = partial trauma / pain

4 = rather trauma / pain

5 = significant trauma / pain and adhesive strength (KK) on a scale of 1 - 5 with

1 = not good adhesion / hold;

2 = rather poor adhesion / hold;

3 = partially good adhesive strength / hold;

4 = rather good adhesive strength / hold; 5 = good adhesive strength / hold rated. The plaster adhesive area was then visually examined for visible corneocyte removal (CA) or covering with skin cells (little = 0-33%, medium = 33-67% and much = 67-100%) and the skin for adhesive residues (yes / no ).

Then the plaster was stuck in the same place five more times and removed again; It was evaluated how often the patch can be repositioned (R, 0-5 times) without losing any of the individually felt adhesive force.

The values of all test subjects were statistically averaged and the standard deviations were determined.

Glass transition temperature Tg (measurement method G):

The static glass transition temperature is determined using dynamic differential calorimetry in accordance with DIN EN ISO 11357-2. The information on the glass transition temperature Tg relates to the glass transition temperature value Tg according to DIN 53765: 1994-03, unless otherwise stated in the individual case.

Moisture penetration rate (MVTR, test method H):

The moisture penetration rate was determined according to the standard DIN EN 13726-2: 2002-06 (test method for primary dressings (wound dressings), part 2: moisture penetration rate of permeable film dressings). This standard is a so-called "gravimetric cup method". Here, beakers are filled with a defined amount of water and their opening (10 cm ² ) is covered with the test material. The measuring vessel is placed in a climatic cabinet with constant temperature (37 ± 1 ° C) and air humidity (relative air humidity <20%). The loss of water in the measuring vessel is determined after a defined time.

In Vitro Cytotoxicity (Test Method I):

The in vitro cytotoxicity was determined according to the ISO 10993-5 standard. The test result is "passed" or "failed". Preparation of the copolymers:

A reactor conventional for radical polymerizations was charged with monomers and solvents as indicated below. After nitrogen gas had been passed through for 45 minutes, the reactor was heated to a jacket temperature of 70 ° C. with stirring. 50 g of AIBN, dissolved in 950 g of ethyl acetate, were added at an internal temperature of 65 ° C. After the exothermic phase, an internal reactor pressure of 0.49 bar was set and polymerization was continued at the constant outside temperature. One hour after the start, 50 g of AIBN, dissolved in 950 g of ethyl acetate, were again added; a further hour later, an internal reactor pressure of 0.59 bar was set.

5.5 h and 7 h after the start, 150 g of bis (4-tert-butylcyclohexyl) peroxydicarbonate, each dissolved in 2.85 g of ethyl acetate, were used for the further initiation. After a reaction time of 22 h, the polymerization was stopped and the mixture was cooled to room temperature. The product which was flushed out of the reactor with the aid of further ethyl acetate had a solids content of 55.7% and was dried.

The resulting polymer parameters are given below.

In Table 1:

AA - acrylic acid nBA - n-butyl acrylate

2-EHA - 2-ethylhexyl acrylate iOA - i-octyl acrylate

MA - methyl acrylate

GlyMA - glycidyl methacrylate.

A mixture of ethyl acetate / isopropanol in the weight ratio given in brackets was used as the solvent. Table 1: Polymerization - amounts of monomers and solvents

Table 2: Polymer parameters

Manufacture of adhesive formulations:

Method 1: Solvent based manufacturing

In the absence of UV light, 227.5 g of polymer and 97.5 g of plasticizer and 194 ml (175 g) of ethyl acetate were weighed into a sample vessel and dissolved with stirring. After a homogeneous mixture had formed, the solution was applied to a PET film provided with a separating layer (75 μm layer thickness) by means of a doctor blade in such a way that adhesive weights of 50 or 100 μm were obtained after drying. Drying was carried out at 30 ° C for 3 hours.

The dried samples were measured using a mercury vapor lamp in a UV curing system of the Eltosch dryer combination, 560 UVLGR (160 / SL) + inert system with Hg UV lamp (power density: 160 W / cm) from Eltosch at a web speed of 4 m / min with a UVC dose of 180 mJ / m ² (M11-M17: 120 mJ / m ² ). The light output was measured using an EIT UV Power Puck II radiometer the company EIT Inc. determined. The wavelength ranges for the performance data of the measured UV light are defined according to the device manufacturer's specifications as follows: UVA (320-390 nm), UVB (280-320 nm), UVC (250-260 nm), UVV (395-445 nm).

The adhesives obtained are listed in Table 3 and the test results thus obtained are listed in Table 4.

Table 3: Adhesives from solvent-based production according to method 1

DINCH - 1,2-cyclohexanedicarboxylic acid diisononyl ester The white oil used was a mixture of pharmaceutical white oils W 505 / W 530 (Fuchs Europe Lubricants GmbH, Germany) in a weight ratio of 1: 1. Table 4: Test results

T - trauma

KK - adhesive strength

R - Repositionability CA - Corneocyte removal

PS - paper splitting nb - not determined In a further series of experiments, a thermal crosslinker was polymerized into the polymer chain (P11) and, on the other hand, crosslinkers were added as additives to the finished polymer. The masses were produced in accordance with process 1, the systems provided with thermal crosslinking agents being finally dried in a heating cabinet at a temperature of 120 ° C. for 15 minutes and crosslinked in the process. The formulations are shown in Table 5. The proportions of the crosslinkers added as an additive are based on the total weight of the mass.

The test results are shown in Table 6.

Table 5: Adhesives

Erisys® GA-240 tetrafunctional epoxy resin Chivacure ^® 300 oligomeric polyfunctional a-hydroxyketone

Table 6: Test results

In a further series of experiments, formulations with breathability-improving additives (“MVTR additive”) were prepared in accordance with process 1. The formulations are shown in Table 7. The proportions of the respective MVTR additives are based on the total weight of the formulation. The test results are shown in Table 8.

Table 7: Adhesives

PEG - polyethylene glycol, (Carbowax ™ PEG 1000, Dow)

Span 80 - sorbitan monooleate

Tween 60 - polyoxyethylene (20) sorbitan monostearate

Table 8: Test results

Method 2: melt-based production

The base polymer was melted using barrel melt and metered into a twin-screw extruder under a pressure of 5 bar. In addition, the liquid plasticizer and / or the MVTR additive were metered into the twin-screw extruder. After the individual components had been mixed sufficiently, the melt was transferred to a siliconized PET film (75 μm layer thickness) via a slot nozzle for flat shaping. The process parameters with regard to the jacket temperature and speed were selected in the twin-screw extruder so that the temperature of the melt at the die outlet - measured using an IR thermometer from Fluke, type Ti20 - was 35 ° C (when using P12 or P13 at 120 ° C) . The coating by means of a nozzle was carried out in such a way that a

Curtain was formed at a distance of 2 cm in front of the coating roller. The web speed of the siliconized PET liner was adjusted so that the coated product had the desired amount of adhesive. The coated adhesive web was passed over a cooling roll (roll temperature = 20 ° C.) through a UV station in such a way that the web was exposed to the UVC dose given in the tables above. The light required in the UVC range was generated by means of a mercury vapor lamp and regulated according to the required dose by an aperture system.

All of the bulk formulations generated above with process 1, except for M18 and M19, could be reproduced without problems in the melt-based process. The test results obtained in this way corresponded to those given in the tables above, with the exception of minimal deviations within the measurement tolerances.

Claims

1. Containing adhesive for sticking to the skin

a) at least one copolymer comprising a monomer composition

at least one (meth) acrylic acid alkyl ester,

has at least one photoinitiator returned; and b) at least one carboxylic acid ester containing at least 10 carbon atoms.

2. Adhesive according to claim 1, characterized in that the monomer composition comprises at least two (meth) acrylic acid alkyl esters.

3. Adhesive according to one of claims 1 and 2, characterized in that the monomer composition

at least one (meth) acrylic acid alkyl ester containing 1 to 6 carbon atoms in the alkyl radical, and

comprises at least one (meth) acrylic acid alkyl ester containing 7 to 12 carbon atoms in the alkyl radical.

4. Adhesive according to one of the preceding claims, characterized in that the monomer composition comprises methyl acrylate and / or n-butyl acrylate.

5. Adhesive according to one of the preceding claims, characterized in that the carboxylic acid ester is a cycloalkylcarboxylic acid ester.

6. Adhesive according to one of the preceding claims, characterized in that the adhesive contains carboxylic acid esters, containing at least 10 carbon atoms, to a total of 5-60% by weight.

7. Adhesive according to one of the preceding claims, characterized in that the adhesive contains at least one compound comprising at least one polyethylene glycol sequence.

8. Adhesive according to one of the preceding claims, characterized in that the adhesive contains at least one polyethoxylated sorbitan ester.

9. Adhesive according to one of the preceding claims, characterized in that the adhesive contains compounds comprising at least one polyethylene glycol sequence in a total of 0.5 to 5 wt .-%.

10th edition for gluing on the skin, comprising a carrier material and

an adhesive according to any one of the preceding claims.

11. A skin-wearable medical device comprising

an adhesive according to any one of claims 1 to 9 and

a medical system.

12. Use of an adhesive according to one of claims 1 to 9 for the production of bonds on the skin.