WO2008086915A1

WO2008086915A1 - Cyanoacrylic acid ester adhesive containing polyester and a plasticizer

Info

Publication number: WO2008086915A1
Application number: PCT/EP2007/063323
Authority: WO
Inventors: Andreas Ferencz; Hanns Misiak; Stefan Kreiling; Kenneth N. Broadley; Colette Hoare
Original assignee: Henkel Ag & Co. Kgaa
Priority date: 2007-01-19
Filing date: 2007-12-05
Publication date: 2008-07-24
Also published as: DE102007003768A1; EP2109646A1

Abstract

The invention relates to adhesive compositions containing at least one cyanoacrylic acid ester, at least one polyester and at least 10 % in weight of at least one plasticizer. The invention also relates to a method for producing said type of adhesive compositions, to the use thereof for medical purposes and to the use of at least one polyester in the production of cyanoacrylate-adhesives in order to increase the tensile strength and/or the modulus of elasticity during the hardening process.

Description

Polyester and plasticizer-containing cyanoacrylate adhesives

The present invention relates to polyester and plasticizer-containing cyanoacrylic acid ester adhesives (cyanoacrylate adhesives), their preparation and use, in particular for medical purposes.

Cyanoacrylate-based adhesives are used in various medical fields, such as suture-free wound closure or laparoscopic surgery.

One of the disadvantages of the known cyanoacrylate adhesives is that they are usually very thin-bodied and therefore, for example, run off the target tissue during wound bonding and thus can only be used in a targeted manner and in an optimal amount. In addition, the adhesive bonds obtained with conventional cyanoacrylate adhesives have a certain brittleness, which become brittle at a movement apart of the bonded parts or fabric and thus put the adhesive success in question.

Various attempts have been made to counteract the above-mentioned undesirable properties by adding to the cyanoacrylate adhesives, for example, organic or inorganic fillers and thickeners to increase the viscosity. However, it has proven to be disadvantageous that in the case of such mixtures phase separation between cyanoacrylate and admixture takes place even before the adhesives cure, which in turn can be partially prevented only by admixing special stabilizers.

In US 3,527,841, for example, polylactic acid is used as a viscosity-influencing agent. US 5,350,798 describes cyanoacrylate-based adhesives containing polyoxalates as reactive plasticizers and thickeners. Polyester-containing, plasticizer-free or only minor amounts of plasticizer-containing formulations are for example, also known from JP 63-284279 A, JP 60133082 A, WO 00/72761 A1, or US 2005/0042197 A1. On the other hand, cyanoacrylate adhesives having plasticizer contents of up to 16% by weight are also described in US Pat. No. 5,981,621 or WO 97/31598.

As the structure of the bond in the cured state stabilizing admixture so-called core-shell particles are known, for example from the toughening. Such core-shell particles have the advantage over the addition of plasticizers that they are non-volatile and evaporate for extended periods of time, and are also unable to migrate. However, cyanoacrylate adhesives containing core-shell particles are also subject to a certain separation behavior during their storage and are also economically disadvantageous due to their complex production.

There was therefore a need for cyanoacrylate adhesives, on the one hand as homogeneously storable, on the other hand have a structural reinforcement in the cured state and still have the necessary flexibility to ensure comfort after application to the tissue to be bonded with subsequent curing and improved adhesion also on flexible substrates. Particularly desirable is a combination of these properties with improved skin compatibility, which is characterized, for example, by reduced skin reactions and irritations and improved permeability to moisture, for example. Also, the biodegradability should be improved over conventional cyanoacrylate adhesives.

Impact-resistant cyanoacrylate adhesive compositions based on high molecular weight polyesters are known, for example, from EP 0 530 626 A1. Although they have an improved impact resistance compared to the unmodified adhesive compositions, but are hardly flexible and break even at low bending stress.

On the other hand, EP 0 098 877 A1 describes the use of elastomers to give toughenes cyanacrylate-based adhesives. The object of the present invention was therefore to provide such cyanoacrylate adhesives which do not have the abovementioned disadvantages and possess the aforementioned positive properties and which are distinguished, in particular, by easier applicability to the surfaces to be bonded and better wearing comfort and which better Have durability in the adhesive bond.

Surprisingly, it has been found that the stated object can be achieved by providing an adhesive composition comprising at least one cyanoacrylic acid ester and at least one polyester and at least 10% by weight of a plasticizer, preferably ester based, based on the total weight of the adhesive composition.

The cyanoacrylates present in the adhesive compositions according to the invention may be both biscyanoacrylates and monocyanacrylic acid esters.

Preferred representatives of the cyanoacrylic acid esters of the latter category can be described by the general formula (I)

R

(I) where

R represents a substituted or unsubstituted, branched or linear alkyl, alkenyl, cycloalkyl, aryl, alkoxyalkyl, or aralkyl group. If the abovementioned groups are substituted, the substituents are preferably one or more hydroxyl groups, amino groups, thiol groups and / or halogen atoms and optionally one or more ether oxygen atoms. If R is an alkyl radical, this preferably contains 1 to 16, more preferably 1 to 8 carbon atoms. When R is a cycloalkyl radical, so this preferably contains 3 to 8 carbon atoms. Preferably, R is a methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, pentyl, hexyl, heptyl, octyl, allyl, methallyl, crotyl -, propargyl, cyclohexyl, benzyl, phenyl, cresyl, 2-chloroethyl, 3-chloropropyl, 2-chlorobutyl, trifluoroethyl, 2-methoxyethyl, 3-methoxybutyl and 2-ethoxyethyl group. The aforementioned cyanoacrylates are known to the adhesive expert, cf. Ullmanns's Encyclopaedia of Industrial Chemistry, Vol. AI, p. 240, Verlag Chemie Weinheim (1985) and US Pat. No. 3,254,111 and PS-PS 36 54 340.

Preferred monomers of the formula (I) are the lactoyl, allyl, methoxyethyl, ethoxyethyl, methyl, ethyl, propyl, isopropyl, butyl, octyl, decyl or dodecyl esters of 2-cyanoacrylic acid.

The adhesive composition of the invention may also contain mixtures of several cyanoacrylic acid esters, such as a mixture of butyl cyanoacrylate and octyl cyanoacrylate. Particularly preferred are mixtures of two or more of the following cyanoacrylic acid esters: lactoyl, butyl, octyl, decyl and dodecyl cyanoacrylate.

By "biscyanacrylates" are meant substances having the following general formula (II):

[H ₂ C =C (CN) -CO-O] ₂ R ¹ (II)

Therein R ^{1 is} a substituted or unsubstituted aryl radical having 6 to 40 C atoms, a substituted or unsubstituted alkylaryl radical, a branched or unbranched divalent alkane radical having 2 to 18, in particular 6 to 12 C atoms, which also contains heteroatoms such as halogens and oxygen or may contain aliphatic or aromatic rings. In particular, one or more ester or ether groups may be included. Preferably, however, R ¹ is an alkane radical having 6 to 12 C atoms.

It is important that the biscyanoacrylates are particularly pure. This requirement is fulfilled, for example, by the manufacturing and cleaning methods described below. Essentially, monocyanacrylates with Transesterified diols and the reaction mixtures by fractional crystallization then worked up.

A suitable process for the preparation of biscyanoacrylates consists in reacting 2-cyanoacrylic acid or its alkyl esters of the general formula (I) in which R is a branched or unbranched alkyl radical having 1 to 6 carbon atoms, with diols of the general formula (III)

[HO] ₂ R ² (III)

wherein R ^{2 is} a branched or unbranched divalent alkane radical having 2 to 18 carbon atoms, which may also contain heteroatoms such as halogens and oxygen or aliphatic or aromatic rings, transesterified to Biscyanacrylaten the general formula (II) and then the reaction mixture fractionated crystallization cleans.

A starting product is therefore the monofunctional cyanoacrylic acid or its alkyl ester according to the formula (I). The alkyl radical should be chosen so that the resulting alcohol can be easily removed. The possibilities suitable for this purpose are known to the person skilled in the art from the general transesterification reaction. Preferably, the alcohol is removed by distillation. Therefore, R is a branched or unbranched alcohol radical preferably having 1 to 6 carbon atoms, more preferably having one or two carbon atoms. The monofunctional cyanoacrylic acid ester is stabilized as usual.

The diols of the general formula (III) are divalent primary or secondary alcohols, preferably primary alcohols. The hydroxyl groups may be in any position to each other, but preferably in alpha / omega position. The diols contain 2 to 18 carbon atoms, preferably 6 to 12 carbon atoms. They can be linear, branched or cyclic. The aliphatic radical may also contain an aromatic group or in addition to the hydrogen and carbon atoms and heteroatoms, such as chlorine or oxygen atoms, preferably in Form of polyethylene or polypropylene glycol units. Examples of suitable diols are hexanediol, octanediol, decanediol and dodecanediol.

The cyanoacrylic acid ester is used in excess. The molar ratio of monofunctional cyanoacrylic acid ester to diol is thus at least 2.0: 1, 0, but preferably 2.5: 1, 0, in particular 2.2: 1, 0.

The transesterification is catalyzed by strong acids, in particular by sulfonic acids, preferably by aromatic sulfonic acids, such as p-toluenesulfonic acid. But also naphthalenesulfonic acid and benzenesulfonic acid and acidic ion exchangers are possible. The concentration of the transesterification catalyst should be between 1 and 20% by weight, based on the monofunctional cyanoacrylate.

The transesterification takes place - as usual - in solution. The solvents used are aromatics and halogenated hydrocarbons. Preferred solvents are toluene and xylene. The concentration of the solution is in the range of 10 to 50, preferably 10 to 20 wt .-%.

The resulting monohydric alcohol or the resulting water are removed in a known manner, preferably distilled off with the solvent. The conversion of the transesterification is controlled for example by NMR spectra. In the case of toluene as a solvent and p-toluenesulfonic acid as a catalyst, the reaction is complete after 10 to 15 hours, that is, no more separates from alcohol.

It is important to work up the reaction mixture. In the case of acidic ion exchangers as a catalyst, these can be easily filtered off. In the case of soluble sulfonic acids as a catalyst, for example of p-toluenesulfonic acid, this is separated off by solvent substitution: toluene is replaced by a mixture of hexane, heptane or decane. After two-fold fractional crystallization gives pure biscyanacrylate. The purity is more than 99% according to NMR spectra. The Biscyanacrylat obtained is stable in storage with the usual stabilizers and in the usual concentrations, ie it changes at 20 ⁰ C within 6 months of its melting point substantially not.

However, the biscyanoacrylates obtained polymehs very fast in the presence of bases, preferably almost as fast as the corresponding monocyanacrylate. As with monofunctional cyanoacrylates, traces of water are already sufficient. The result is a three-dimensionally crosslinked polymer with relatively good thermal properties.

Both monofunctional cyanoacrylates and biscyanoacrylates are therefore stabilized, for example, with sulfur dioxide, which is able to bind even the smallest amounts of moisture to form sulfuric acid. Further suitable stabilizers are, for example, boron trifluoride and butylated hydroxyanisole (BHA).

The content of cyanoacrylic acid ester (A) in the adhesive composition according to the invention is preferably up to 89.5% by weight, based on 100% by weight of the adhesive composition. The content of cyanoacrylic acid ester (A) is particularly preferably 50 to 80% by weight and very particularly preferably 60 to 75% by weight, based on 100% by weight of the adhesive composition.

In a particular embodiment, however, some of the cyanoacrylic acid esters (A) may be partially oligomerized and / or polymerized. Oligomers of cyanoacrylates (A) are short-chain polymerization products of cyanoacrylates (A) with up to 10 copolymerized monomer units. Polymers are understood as meaning those polymerization products of the cyanoacrylic acid esters (A) which contain more than 10 monomer units. If part of the cyanoacrylates (A) is oligomerized and / or polymerized, this proportion is preferably at least 1% by weight, based on cyanoacrylic acid ester (A), especially preferably at least 2% by weight and very particularly preferably at least 3% by weight, based on cyanoacrylic acid ester (A).

The adhesive compositions according to the invention also contain at least one polyester (B) in addition to the at least one cyanoacrylic acid ester (A). For the purposes of the present invention, the term "polyester" refers to polymers having ester bonds in their main chain, and thus neither low molecular weight compounds having a plurality of ester groups, such as, for example, thacetin, nor polymers having ester groups in the side chain, such as, for example, polyvinyl acetates or polyacrylates, are used here Concept of polyester.

The polyesters as used in the adhesive compositions according to the invention are generally obtained by polycondensation of diols and dicarboxylic acids or derivatives thereof. However, it is also possible to prepare them by polycondensation of hydroxycarboxylic acids or by ring-opening polymerization of lactones. Instead of diols and dicarboxylic acids and polyols and / or polycarboxylic acids can be used, resulting in branched polyesters. The polyesters used according to the invention are preferably prepared by polycondensation of one or more polyols, in particular diols with one or more polycarboxylic acids, in particular dicarboxylic acids.

The diols suitable for the synthesis of the polyester are, for example, 1,2-ethanediol, 1,2-propanediol, 1,3-propanediol, dihydroxyacetone, 2-methyl-1,3-propanediol, 2-butyne-1,4-diol, 3 Butene-1, 2-diol, 2,3-butanediol, 1, 4-butanediol, 1, 3-butanediol, 1, 2-butanediol, 2-butene-1, 4-diol, 1, 2-cyclopentanediol, 3 -Methyl-1,3-butanediol, 2,2-dimethyl-1,3-propanediol, 4-cyclopenten-1, 3-diol, 1, 2-cyclopentanediol, 2,2-dimethyl-1,3-propanediol, 1 , 2-pentanediol, 2,4-pentanediol, 1,5-pentanediol, 4-cyclopenten-1, 3-diol, 2-methylene-1,3-propanediol, 2,3-dihydroxy-1,4-dioxane, 2 , 5-dihydroxy-1, 4-dithiane, diethylene glycol, wherein among these preferably 1, 2-propanediol and diethylene glycol are used. Other suitable diols are based on higher oligomers or polymers of aforementioned diols such as polyethylene glycol, polypropylene glycol, polytetrahydrofuran.

In a preferred embodiment, it is also possible to use mixtures of two or more diols. If mixtures of two or more diols are used, it is advantageous if a sufficient proportion of hydrophilic diols is used.

A hydrophilic diol is understood as meaning a diol which contains a maximum of 3 methylene groups or a polyether diol composed of such an alcohol. If, for example, a mixture of 1,2-propanediol and diethylene glycol is used, the molar proportion of diethylene glycol preferably predominates in the mixture.

If polyols having more than two hydroxyl groups are used, those having from 3 to 6 hydroxyl groups are preferred. Examples of triols which may be mentioned are glycerol or trimethylolpropane. Polyols with four to six hydroxyl groups are z. As the hemiacetals of aldofumaroses such as D-erythrose and D-threose or hemiacetals of aldoses such as D-ribose, D-arabinose, D-xylose or D-lyxose.

The term "dicarboxylic acids and their derivatives" is to be understood as meaning all hydroxy-reactive derivatives of dicarboxylic acids such as dicarboxylic acid anhydrides, dicarboxylic acid halides, dicarboxylic acid esters, dicarboxylic acid azides Preferred dicarboxylic acids are, for example, oxalic acid, malonic acid, succinic acid, glutaric acid, adipic acid, pimelic acid, azelaic acid, suberic acid, tetrahydrophthalic acid, 4 Methyltetrahydrophthalic acid, hexahydrophthalic acid, 4-methylhexahydrophthalic acid phthalic acid, isophthalic acid, terephthalic acid, fumaric acid, maleic acid, trimellitic acid, particularly preferably oxalic acid, malonic acid, succinic acid, glutaric acid, phthalic acid, isophthalic acid, terephthalic acid and among these most particularly preferred as aromatic dicarboxylic acids phthalic acid and isophthalic acid and their Derivatives and used as aliphatic dicarboxylic acids adipic acid and derivatives thereof. Examples of preferred polycarboxylic acids having more than two carboxy functionalities are trimerized linoleic acid, trimellitic acid or pyromellitic acid.

In a preferred embodiment, however, the polyesters are linear polyesters prepared from diols and dicarboxylic acids. It is particularly preferred if at least some of the dicarboxylic acids originate from the group of aromatic dicarboxylic acids and derivatives thereof. Very particularly suitable aromatic dicarboxylic acids and derivatives thereof are phthalic acid and isophthalic acid and their anhydrides or esters.

In a particular embodiment, the polyesters used according to the invention have exclusively ester groups along their chain and are free of other linking groups, such as, for example, urethane groups.

The polyesters used in the invention preferably have an average molar mass of from 200 to 20 000 g / mol, more preferably from 300 to 10 000 g / mol and most preferably from 500 to 5000 g / mol. The average molar mass is determined from the OH number and the functionality of the polyesters known from the preparation process. If the molar mass is above 20,000 g / mol, the increase in viscosity may be so extreme that not enough material can be introduced into the formulation; if it is below 200 g / mol, the change in compatibility with the curing cyanoacrylate matrix may be too low.

The polyesters used in the adhesive compositions according to the invention preferably have an OH number up to 800 mg KOH / g, more preferably from 10 to 400 mg KOH / g and most preferably from 20 to 250 mg KOH / g. The acid number of the polyesters is preferably below 10 mg KOH / g, more preferably below 5 mg KOH / g and most preferably below 2 mg KOH / g. In a particularly favorable embodiment, the polyesters to be used according to the invention have no free carboxyl groups. Preferably, the proportion of the polyester in the total mass of the adhesive composition according to the invention is at least 0.5 wt .-%, such as 0.5 to 25 wt .-%, particularly preferably 1 to 15 wt .-% and most preferably 2 to 10 wt .-%.

The polyesters contained in the compositions according to the invention are preferably selected so that they are as neutral as possible to the skin, i. Skin irritation or irritation can be avoided. The choice is preferably made with the screening tests known to one of ordinary skill in the cosmetic art.

In another preferred embodiment, the polyester (B) is chosen to increase the viscosity and thus control the fluidity of the composition so that the adhesive composition does not flow directly into it after application to the wound, but forms as a film over it , Preferably, this can be achieved in that the average molecular weight of the polyester (B) is more than 10,000 g / mol, the polyester (B) has a block-like structure, which promotes a crosslinking structure and wherein the polarity is adjusted so that the wetting behavior is influenced so that the influx into the wound is reduced.

In addition to the cyanoacrylic acid ester and the polyester, the adhesive composition according to the invention also contains at least 10% by weight of at least one plasticizer.

A "plasticizer" is a liquid or solid, indifferent organic substance with low vapor pressure to understand, which occurs without chemical reaction with high polymer substances in physical interaction and can form a homogeneous system with these (DIN 55945: 1999-07).

The plasticizers used in the present invention are preferably those from the group of esters. Preferably, the plasticizers from the group of esters are partial or full esters, mono- or polybasic carboxylic acids and monohydric or polyhydric alcohols. Become used aliphatic carboxylic acids, they preferably contain 1 to 10, particularly preferably 1 to 5 carbon atoms. If monohydric or polyhydric aliphatic alcohols are used for ester formation, these alcohols preferably have 1 to 10, particularly preferably 1 to 5, carbon atoms. If cycloaliphatic alcohols are used, these preferably contain 3 to 12, particularly preferably 4 to 12, carbon atoms. If aromatic alcohols are used, their number of carbon atoms in the alcohol molecule is preferably from 6 to 12 carbon atoms.

Particularly preferred are those partial or full esters of mono- or polyhydric aliphatic carboxylic acids having 1 to 10 carbon atoms, preferably having 1 to 5 carbon atoms and mono- or polyhydric aliphatic or cycloaliphatic alcohols having 1 to 10 carbon atoms, preferably having 1 to 5 carbon atoms, in which the number of directly linked carbon atoms in the other aliphatic groups is at most 3, when an aliphatic group contains 4 or 5 directly connected carbon atoms.

The alcohol component of the ester used as the plasticizer is preferably alcohols having 1 to 5, in particular having 2 to 4, OH groups and having 2 to 5, in particular 3 or 4, directly linked carbon atoms. The number of non-directly connected carbon atoms can be up to 110, preferably up to 18 carbon atoms.

Examples of monohydric alcohols which are suitable for the production of plasticizers include: methanol, ethanol, 1-propanol, 2-propanol, 1-butanol, 2-butanol, 2,2-dimethyl-1-propanol, 2-methyl-1 propanol, 2,2-dimethyl-1-propanol, 2-methyl-2-propanol, 2-methyl-1-butanol, 3-methyl-1-butanol, 2-methyl-2-butanol, 3-methyl-2 -butanol, 1-pentanol, 2-pentanol, 3-pentanol, cyclopentanol, cyclopentenol, glycidol, tetrahydrofurfuryl alcohol, tetrahydro-2H-pyran-4-ol, 2-methyl-3-buten-2-ol, 3-methyl-2 -but-2-ol, 3-methyl-3-buten-2-ol, 1-cyclopropyl-ethanol, 1-penten-3-ol, 3-penten-2-ol, 4-penten-1-ol, 4 Pentene-2-ol, 3-pentin-1-ol, 4-pentin-1-ol, propargyl alcohol, allyl alcohol, hydroxyacetone, 2-methyl-3-butyn-2-ol. Examples of dihydric alcohols which are suitable for the production of plasticizers include: 1, 2-ethanediol, 1, 2-propanediol, 1, 3-propanediol,

Dihydroxyacetone, thioglycehn, 2-methyl-1,3-propanediol, 2-butyne-1,4-diol, 3-butene-1,2-diol, 2,3-butanediol, 1,4-butanediol, 1, 3 Butanediol, 1, 2-butanediol, 2-butene-1, 4-diol, 1, 2-cyclopentanediol, 3-methyl-1, 3-butanediol, 2,2-dimethyl-1, 3-propanediol, 4-cyclopentene 1, 3-diol, 1, 2-cyclopentanediol, 2,2-dimethyl-1,3-propanediol, 1, 2-pentanediol, 2,4-pentanediol, 1, 5-pentanediol, 4-cyclopentene-1, 3 diol, 2-methylene-1, 3-propanediol, 2,3-dihydroxy-1,4-dioxane, 2,5-dihydroxy-1,4-dithiane.

Examples of trihydric alcohols which are suitable for the production of plasticizers include: glycehn, erythrulose, 1, 2,4-butanhol, erythrose, threose, trimethylolethane, trimethylolpropane and 2-hydroxymethyl-1, 3-propanediol.

Examples of tetrahydric alcohols which are suitable for the production of plasticizers include: erythritol, threitol, pentaerythritol, arabinose, ribose, xylose, ribulose, xylulose, lyxose, ascorbic acid and gluconic acid Y-lactone.

As examples of pentahydric alcohols which are suitable for the production of plasticizers may be mentioned: arabitol, adonite and XyNt.

The polyhydric alcohols described above can be used in etherified form in a particular form of the invention. The ethers can be prepared, for example, by condensation reactions, Williamson's ether synthesis or by reaction with alkylene oxides such as ethylene, propylene or butylene oxide from the abovementioned alcohols. Examples which may be mentioned are: diethylene glycol, triethylene glycol, polyethylene glycol, diglycerol, triglycerol, tetraglycehn, pentaglycehn, polyglycerol, technical mixtures of the condensation products of glycerol, glycerol propoxylate, diglycerol propoxylate, pentaerythritol ethoxylate, dipentaerythritol, ethylene glycol monobutyl ether,

Propylene glycol monohexyl ether, butyl diglycol, dipropylene glycol monomethyl ether.

For the esterification, mixtures between the above-mentioned mono- or polyhydric alcohols can also be used. Examples of monohydric carboxylic acids which can be used for the esterification with the abovementioned alcohols are: formic acid, acrylic acid, acetic acid, propionic acid, butyric acid, isobutyric acid, valeric acid, isovaleric acid, 2-oxovaleric acid, 3-oxovaleric acid, pivalic acid, acetoacetic acid, levulinic acid, 3-methylpentanoic acid. 2-oxo-butyric acid, propiolic acid, tetrahydrofuran-2-carboxylic acid, methoxyacetic acid, dimethoxyacetic acid, 2- (2-methoxyethoxy) -acetic acid, 2-methylacetic acid, pyruvic acid, 2-methoxyethanol, vinylacetic acid, allylacetic acid, 2-pentenoic acid, 3-pentenoic acid and tetrahydrofuran-2-carboxylic acid.

Examples of polybasic carboxylic acids which may be mentioned are: oxalic acid, malonic acid, fumaric acid, maleic acid, succinic acid, glutaric acid, acetylenedicarboxylic acid, oxalacetic acid, acetonedicarboxylic acid, mesoxalic acid, citraconic acid, dimethylmalonic acid, methylmalonic acid and ethylmalonic acid.

Hydroxycarboxylic acids can also be used as starting materials, eg. Tartronic, lactic, malic, tartaric, citramalic, citric, 2-hydroxyvaleric, 3-hydroxyvaleric, 3-hydroxybutyric, 3-hydroxyglutaric, dihydroxyfumaric, 2,2-dimethyl-3-hydroxypropionic, dimethylolpropionic and glycolic acids.

The esterification can be either complete or partial. It is also possible to use mixtures of the acids mentioned for the esterification.

The plasticizers from the group of esters which are to be used according to the invention and are prepared from the abovementioned alcohols and carboxylic acids or the corresponding derivatives are preferably free of catalysts, in particular of alkali metals and amines. This can be achieved by treating the esters according to the invention with acids, ion exchangers, acetic clays, aluminum oxides, activated carbon or other auxiliaries known to the person skilled in the art. For drying and further purification, for example, can be distilled overhead. Examples of the plasticizers from the group of esters used according to the invention include: ethyl acetate, butyl acetate, glycerol triacetate, glycehntripropionate, triglycerol pentaacetate, polyglycerol acetate, diethylene glycol diacetate, ethyl 3-hydroxyvalerate, butyl lactate,

Lactic acid isobutyl ester, ethyl 3-hydroxybutyrate, diethyl oxalate, diethoxalate, dimethyl malate, diisopropyl maleate, diethyl tartaric, dipropyl tartaric acid, diisopropyl tartrate, dimethyl glutarate, dimethyl succinate,

Diethyl succinate, diethyl malonate, diethyl fumarate, diethyl malonate, 2-hydroxyethyl acrylate,

Oxovaleric acid methyl ester, glycehniacetate, glycerol tributyrate,

Glycehn dipropionate, glycerol triisobutyrate, glycerol diisobutyrate, glycidyl butyrate, butyl acetoacetate, levuanic acid ethyl ester,

Hydroxyglutaric acid dimethyl ester, glycehnacetate dipropionate,

Glycehndiacetate butyrate, Propiolsäurebutylester, Propylenglykoldiacetat,

Propylene glycol dibutyrate, diethylene glycol dibutyrate, trimethylol ethane acetate, trimethylolpropane acetate, trimethylol ethane tributyrate, neopentyl alcohol dibutyrate, methoxyacetate, butyl dimethoxyacetate, and

Glycolate. Particularly preferred as a plasticizer is triacetin.

Particularly preferably, the plasticizers used in the adhesive composition according to the invention have a molecular weight of up to 600, better up to 500, even better up to 400 and most preferably up to 300 g / mol.

The plasticizer (s) contained in the adhesive composition are present in a concentration of at least 10% by weight, preferably at least 15% by weight, such as at least 16, at least 17 or at least 18% by weight, based on the total weight of the adhesive composition , The plasticizer content is particularly preferably at least 20% by weight, more preferably at least 25% by weight, based on the total mass of the adhesive composition. However, the plasticizer content should preferably not exceed 50% by weight. Since almost all plasticizers used in the adhesives according to the invention are biodegradable to harmless products, the present invention makes it possible, in a particularly preferred embodiment, to provide adhesive compositions even with minimal use of the reactive cyanoacrylic acid esters, ie a high proportion of plasticizers show an excellent adhesive properties and yet are readily biodegradable and due to the low Cyanacrylsäureester- share tissue irritation as much as possible avoided.

Another advantage of the adhesive compositions of the invention is also that the cured adhesive film is superficially leachable, giving the film a desired dull appearance. In contrast to a glossy film, a matt film is noticeably less noticeable, for example, on parts of the skin that are to be glued or bonded together, and is therefore preferred in terms of wound cosmetics.

It is also possible to choose from the plasticizers mentioned above those which have skin-care properties, which also promotes secondary wound healing.

If one observes the course of curing of the adhesives in the tensile elongation test, surprisingly, even with high amounts of plasticizer in the adhesive compositions of the invention compared to the respective polyester-free compositions significantly higher elastic moduli (Ei ₀ ) and tensile strengths (σi), although the tear strength (σ _max ) and only slightly differentiate the elongation at break. Thus, in the course of curing, σ i and / or Ei _{0 are} preferably at least 10% higher than the corresponding sizes in corresponding adhesive compositions without polyester content.

Another object of the invention is therefore also the use of at least one polyester to increase the tensile strengths and / or moduli of elasticity during curing in adhesive compositions containing at least a cyanoacrylic acid ester and at least one plasticizer, preferably from the group of esters.

In a particular embodiment of the aforementioned use, the adhesive composition contains at least 12% by weight, preferably at least 15, 16, 17 or 18% by weight of a plasticizer, preferably from the group of esters, more preferably at least 20, 22, 23 or 25 Wt .-% of a plasticizer, preferably from the group of esters based on the total weight of the adhesive composition.

In a further particular embodiment of the above-mentioned use, the adhesive composition contains from 2 to 15% by weight of the polyester, preferably from 2 to 10% by weight of the polyester, based on the total weight of the adhesive composition.

In addition, other additives may also be included, such as thickeners, stabilizers, activators, dyes, antioxidants, fillers, thixotropic agents, colorants, UV absorbers, radical inhibitors, aging inhibitors, fluorescent markers, odors and

Hardening accelerator, z. As polyethylene glycol or cyclodextrin and polymers. However, wound healing promoting substances such as antibiotics or drugs and the like may also be physically polymerized into the resulting polymer or chemically incorporated into the resulting polycyanoacrylate.

In principle, all substances which are suitable for increasing the "consistency" of the dispersion according to the invention, ie for making the dispersion more viscous, are suitable thickeners, the consistency being highly correlated with the rheological properties of the medium It does not matter if the thickener acts associatively or gelling or otherwise, and the thickeners mentioned are preferably selected from natural, modified natural or fully synthetic organic macromolecules. The modification of natural substances is usually done by polymer-analogous reactions z. B. be carried out on the free hydroxyl groups of polysaccharides.

Particularly preferred thickening components here are methylcellulose (MC), hydroxyethylcellulose (HEC) and carboxymethylcellulose (CMC). Other likewise preferred derivatives of natural thickeners are, for. Hydroxypropylmethylcellulose (HPMC), hydroxypropylcellulose (HPC) and ethylhydroxyethylcellulose (EHEC). In addition, analogous starch derivatives, eg. For example, hydroxyethyl starch and hydroxypropyl starch are preferred.

For the purposes of the present invention, it is likewise preferred if the said thickeners optionally contained are selected from the groups of

- Synthetic and polymeric thickener, in particular from the group of polysaccharides, especially xanthan gum, guar-guar, agar-agar, alginates and Tylose, carboxymethylcellulose and hydroxyethylcellulose, also higher molecular weight polyethylene glycol mono- and diesters of fatty acids, polyacrylates, (z. Carbopols from Goodrich or Synthalene from Sigma), polyacrylamides, polyvinyl alcohol and polyvinylpyrrolidone,

the silicatic thickener, in particular selected from the group of silicic acids or phyllosilicates (for example Aerosil, Sipernat or Optibent from Südchemie).

- The surfactants, in particular synthetic thickener polymers are preferred. These have, like natural polymers, substituents that cause aggregation with water molecules. Moreover, they can also be derivatized by hydrophobic groups as well, giving them surfactant properties. As a result, they act as associative thickeners or as protective colloids in the suspension polymerization. Particularly preferred fully synthetic thickeners within the scope of the dispersion according to the invention are polyvinyl alcohols, poly (meth) acrylic acids and their salts, polyacrylamides, poly (vinylpyrrolidone) and polyethylene glycols and also polypropylene glycols and copolymers thereof. A raw material available on the market is the product Poloxamer 407. Other preferred thickeners within this Category are copolymers of acrylic acid derivatives and maleic acid. Such substances are available, for example, under the name Gantrez from ISP.

The invention also provides a process for the preparation of the adhesive composition according to the invention, in which at least one cyanoacrylic acid ester, at least one polyester and at least 10 wt .-% of at least one plasticizer, preferably from the group of esters, based on the total weight of the adhesive composition and optionally further additives are mixed so that they form a substantially clear solution prior to the polymerization of the at least one cyanoacrylic acid ester.

Finally, the invention also relates to a cured adhesive composition which is obtained by curing the adhesive compositions of the invention comprising at least one cyanoacrylic acid ester, at least one polyester and at least 10% by weight of at least one plasticizer from the group of the esters, based on the total weight of the adhesive composition. In the cured adhesive composition preferably at least a portion of the polyester and / or a portion of the plasticizer is in the form of a plurality of particles phase-separated before in the respective surrounding phase. By the term "cure" is meant the reaction between the unsaturated bonds of the cyanoacrylic acid esters contained in the adhesive composition of the present invention, with complete cure when substantially all of the unsaturated bonds available for reaction are reacted in that the compatibility between the added polyester and / or the plasticizer, on the one hand, and the cyanoacrylate polymer which forms, on the other hand, decreases until this results in at least partial separation of the components, preference being therefore given to those adhesive compositions in which, in the uncured state, the polyester or Plasticizers are clearly dissolved and in the cured state of or the polyesters or the plasticizer (s) are phase separated in the adhesive composition.

The phase-separated particles preferably have a size of 50 nm to 200 μm, more preferably 100 nm to 20 μm. In this case, the phase-separated particles are substantially homogeneously distributed in the cured, that is to say polymerized, cyanoacrylic acid ester or the matrix consisting of polymerized cyanoacrylic acid ester and the non-phase-separating constituents. The particle sizes of the phase-separated particles can be easily determined by scanning electron microscopy or transmission electron microscopy after ruthenium oxide or osmium oxide contrasting of freeze fractions or ultrathin sections of the samples, in the manner known to those of ordinary skill in the art. A phase separation can be detected in this way even with optically clear samples, if appropriate.

Specifically, the polyester component can be chosen such that the phase separation occurs in a core-shell morphology when the adhesive composition is fully or partially cured. For this purpose, for example, either a polyester blend or a polyester with a broad or multimodal molecular weight distribution can be used.

Particular preference is given to adhesive compositions of the invention in which tensile strengths (tensile strengths) σi and / or elastic moduli Ei _{0 are} higher by at least 10%, preferably at least 20%, particularly preferably at least 50% and very particularly preferably at least 70, 80, 90 or 100% than the corresponding sizes in corresponding adhesive compositions without polyester content.

Furthermore, preference is given to those adhesive compositions according to the invention whose values for elongation at break and tear strength (σ _ma χ) differ by not more than 30%, particularly preferably not more than 20%, from the values in corresponding adhesive compositions without polyester content. The invention further relates to the use of the cyanoacrylate ester adhesives according to the invention for medical purposes, in particular for covering, sealing or sealing wounds or surgical interfaces, or for fixing or reinforcing biological tissue or implants. Thus, for example, irritated or injured tissue can be covered, joined or fixed, bleeding or the escape of substances such as body fluids or oxygen can be reduced. For example, superficial as well as deep wounds are treatable, skin as well as internal organs, nerve tissue or blood vessels. Some examples of such medical applications relate to the field of external or internal applications, such as the fixation of devices, such as devices such as injection devices or sensors, but also patches and the like on the skin, wound closure after surgery, the Fixing of plastic meshes used to connect highly loaded tissue connections, closing of lung injuries after sampling or sealing of interfaces in bypass operations. A particular advantage for the medical application is that the choice of the polyester and the plasticizer, the degradation and absorption rate of the material can be controlled. Furthermore, components influencing the healing process can be formulated into the adhesive according to the invention. The adhesive composition of the invention can be sterilized. Furthermore, the adhesive compositions according to the invention can be used in ophthalmology or in the dental field. In addition to use in medical applications, the adhesive compositions of the invention can also be used in the non-medical field, preferably for bonding flexible materials, such as rubber or rubber-elastic materials. In addition, the adhesive compositions according to the invention can also be used in the cosmetic field, for example for fixing hair extensions or to glue eyelashes.

Another object of the invention is the use of the adhesive composition according to the invention for bonding tissue, preferably for bonding human tissue, wherein the polyester (B) is selected so that it behaves tissue or skin neutral.

Finally, the invention also relates to the use of polyesters in the preparation of cyanoacrylate adhesives containing at least one cyanoacrylic acid ester and a plasticizer from the group of esters, wherein the plasticizer is preferably present in an amount of at least 10 wt .-% based on the weight of the total Adhesive composition is included, for increasing the tensile strength and / or the modulus of elasticity.

In the following, the invention is illustrated by means of examples.

Examples

The polyesters A and B used in the examples were synthesized by polycondensation reaction, as known to the polymer chemist, from the components indicated in the following Table 1, which represent the number of moles of the respective component.

Table 1 - Compositions of the polyesters

Polyester A has an OH number of about 139 mg KOH / g, polyester B has an OH number of about 58 mg KOH / g.

Examples 1 to 4

In Examples 1 to 4, adhesive compositions were investigated which contain 30% by weight of thacetin (plasticizers from the group of esters) and different amounts of polymer A: Example 1 (not according to the invention) contains no polyester A, Example 2 contains 2% by weight. %, Example 3 contains 4% by weight and Example 4 contains 10% by weight of Polyester A. The 100% by weight missing portion of the compositions is SO 2 and BHA stabilized n-butyl acrylate.

In the tensile test (according to DIN 53455, with the following variations in temperature and humidity: temperature 21 ⁰ C, relative humidity: 45%) it can be seen that the adhesive compositions of the invention both as to its elasticity modules (E10) and the tensile strengths (.sigma..sub.i) are improved.

E ₁₀ is defined as (according to DIN 53457, with the following deviations in terms of temperature and humidity: temperature 21 ^° C., relative humidity: 45%) Force increase with an elongation of the sample body by 10% compared to the starting position.

The tensile strength G ₁ (according to DIN 53455, with the following variations in temperature and humidity: temperature 21 ⁰ C, relative humidity: 45%) defines a) the tensile stress at yield, in the case that results in a maximum force or b) as Tensile stress at 50% elongation if no clear maximum results (see Fig. 1).

The tensile test is in this case (according to DIN 53455, with the following deviations in terms of temperature and humidity: temperature 21 ⁰ C, relative humidity:

45%), using test piece no. 4 with the following dimensions:

Total length L = 75 mm, measuring length L ₈ = 20 mm, clamping width b _e = 12 mm,

Web width b = 4 mm, the thickness of the test piece is measured and is between 1 and 2 mm. The test speed is 100 mm / min.

To 1.5 g of the adhesive compositions of Examples 1 to 4 were each added a few crystals of 3,5-dibromopyridine as a catalyst, so that the catalyst concentration was about 0.04%. The compositions were then either cast into films and punched at the time of testing according to the specimen shape or poured directly into Teflon molds and removed for testing. Before carrying out the measurements, the samples were cured for 5 hours.

The mixtures according to the invention (Examples 2, 3 and 4) become turbid due to the phase separation to varying degrees. The non-inventive composition remained clear.

The results are shown in Table 2.

Table 2 - Different Polvester shares

Examples 5 to 8

In Examples 5 to 8, adhesive compositions containing different amounts of thacetin (plasticizer from the group of esters) were investigated: Examples 5 and 6 contain 20% by weight of triacetin, Examples 7 and 8 contain 25% by weight of triacetin. Examples 5 and 7 are not according to the invention since they contain no polyester (polymer A). The 100% by weight missing portion of the compositions is SO 2 and BHA stabilized n-butyl acrylate.

The formation of the layers and the curing were carried out as described in Examples 1 to 4, with the exception that in Examples 5 and 6 the curing time was 3 hours instead of 5 hours.

The physical parameters given in Table 3 were determined as described above for Examples 1-4.

Table 3 - Different plasticizer levels

* without polymer A; ** with 4% by weight of polymer A; ⁺ 3h curing; ⁺⁺ 5h curing; Example 9

Example 9 corresponds to Example 3 with the difference that instead of the polymer

A, the polymer B was used.

Table 4 - Different polyesters

4% by weight of polyester; 30% by weight each of triactetin; n-butyl acrylate stabilized with SO ₂ (80 ppm) and butylhydroxyanisole (2500 ppm) to 100% by weight; 5 hours hardening; * the slight haze occurs after the composition first appeared clear.

Claims

claims

An adhesive composition comprising

(A) at least one cyanoacrylic acid ester,

(B) at least one polyester,

(C) at least 10% by weight of a plasticizer based on 100% by weight of the adhesive composition.

2. An adhesive composition according to claim 1, characterized in that the cyanoacrylic acid ester has the general formula (I)

R

(I) where

R is a substituted or unsubstituted, branched or linear alkyl, alkenyl, cycloalkyl, aryl, alkoxyalkyl, or aralkyl group.

3. An adhesive composition according to claim 2, characterized in that R is a substituted or unsubstituted alkyl radical having 1 to 16 carbon atoms, a substituted or unsubstituted cycloalkyl radical having 3 to 8 carbon atoms or a substituted or unsubstituted phenyl radical.

4. Adhesive composition according to one of claims 2 or 3, wherein the radical R is a substituted alkyl, alkenyl, cycloalkyl, aryl, alkoxyalkyl, or aralkyl group and wherein as substituents one or more hydroxy groups, amino groups, thiol groups and / or halogen atoms are contained and / or one or more ether oxygen atoms are contained.

5. An adhesive composition according to claim 2, 3 or 4, wherein R is an alkyl radical having 1 to 12 carbon atoms, preferably a lactoyl radical, butyl radical, octyl radical, decyl radical or dodecyl radical, or mixtures thereof.

6. Adhesive composition according to one or more of claims 1 to

5, wherein the polyester is a linear or branched polyester with einpolymehsierter phthalic acid, isophthalic acid and / or adipic acid.

7. Adhesive composition according to one or more of claims 1 to

6, wherein the polyester has an average molecular weight of 300 to 10,000 g / mol.

8. The adhesive composition according to claim 1, wherein the polyester has an average molecular weight of more than 10,000 g / mol, has a block structure and a polarity which influences the wetting behavior on the fabric and the skin in such a way that the adhesive runs in the wound is reduced or prevented.

9. Adhesive composition according to one or more of claims 1 to

8, wherein the polyester is selected so that it behaves skin-neutral.

10. An adhesive composition according to one or more of claims 1 to

9, wherein the polyester has an OH number of 10 to 400 mg KOH / g.

11. An adhesive composition according to one or more of claims 1 to

10, wherein the content of cyanoacrylic acid ester (s) (A) to 89.5 wt .-% and the content of polyester (s) (B) 0.5 to 25 wt .-% based on 100 wt .-% of the adhesive composition is.

12. An adhesive composition according to one or more of claims 1 to

11, wherein the plasticizer is selected from the group of esters.

13. An adhesive composition according to claim 12, wherein the ester is a partial or full ester of mono- or polybasic carboxylic acids and mono- or polyhydric alcohols.

14. An adhesive composition according to claim 13, wherein the mono- or polybasic carboxylic acids are aliphatic carboxylic acids having 1 to 10 carbon atoms and the monohydric or polyhydric alcohols are aliphatic alcohols having 1 to 10 carbon atoms or aromatic alcohols having 6 to 12 carbon atoms.

15. An adhesive composition according to one or more of claims 1 to

14, wherein the polyester component (B) is selected to be composed of polymerized monomers which give the polyester a core-shell morphology when the adhesive composition is wholly or partially cured.

16. Adhesive composition according to one or more of claims 1 to

15, in which, in the uncured state, the polyester or polyesters (B) and / or the plasticizer (s) (C) are clearly dissolved and in the cured state the polyester or polyesters (B) and / or the plasticizer (s) in the Adhesive composition are at least partially phase-separated.

17. Adhesive composition according to one or more of claims 1 to

16, wherein at least a portion of the at least one polyester (B) and / or at least a portion of the at least one plasticizer (C) is present in the form of a plurality of particles phase-separated in the adhesive composition after its curing.

The adhesive composition according to claim 17, wherein the particles have a size of 50 nm to 200 μm.

19. An adhesive composition according to one or more of claims 1 to 18, wherein this has a tensile strength σi and / or a modulus of elasticity Ei ₀ in the course of curing, which has at least 10% higher values than the corresponding size in corresponding adhesive compositions without polyester content.

20. Adhesive composition according to one or more of claims 1 to 19, wherein a part of the cyanoacrylate (A) is partially oligomehsiert and / or polymerized.

21. An adhesive composition according to claim 20, wherein at least 1 wt .-% of the cyanoacrylate (A), preferably at least 2 wt .-% and particularly preferably at least 3 wt .-% of the cyanoacrylate (A) is oligomerized and / or polymerized.

A method of making an adhesive composition of one or more of claims 1 to 21, wherein the components are mixed to result in a substantially clear solution.

23. Use of the adhesive composition of one or more of claims 1 to 21 or prepared by the method according to claim 22 for medical and non-medical purposes.

24. Use according to claim 23, wherein the adhesive composition is used for internal and / or external application.

25. Use according to claim 23 or 24, wherein the adhesive composition is for bonding flexible materials.

26. Use of at least one polyester in the preparation of cyanoacrylate adhesives containing at least one cyanoacrylic acid ester and a plasticizer from the group of esters for increasing the tensile strength and / or the modulus of elasticity during the curing process.

Use of the adhesive composition of one or more of claims 1 to 21 or prepared by the method of claim 22 for bonding tissue, wherein the polyester (B) is selected to be tissue neutral.