DE102007019043A1 - Use of a surface modifying composition comprising a component from monomolecular, oligomer and/or polymer flow retarding agent, for the preparation of a kit for the topical and/or internal application on tissue - Google Patents

Abstract

Use of a surface modifying composition (I) for the preparation of a kit for the topical and/or internal application on tissue, is claimed, where: the composition comprises at least a component from monomolecular, oligomer and/or polymer flow retarding agent, which is suitable to initiate the polymerization of a polymerizable monomer adhesive composition on the tissue surface and to accelerate and/or to obtain a flowable product of the monomer polymerizable adhesive composition during the application on the tissue surface. Use of a surface modifying composition (I) for the preparation of a kit for the topical and/or internal application on tissue, is claimed, where: (I) comprises at least a component from monomolecular, oligomer and/or polymer flow retarding agent, which is suitable to initiate the polymerization of a polymerizable monomer adhesive composition on the tissue surface and to accelerate and/or to obtain a flowable product of the monomer polymerizable adhesive composition during the application on the tissue surface; the amount of the flow retarding agent or its mixture is 0.001-40 wt.%; at least 30% of the monomer, oligomer and/or polymer flow retarding agent contains at least a functional group of ammonium, amide, amine, anhydride, carbonyl, carbozylate, ether, ester, hydroxyl, formamide, imide, lactone, lactam, sulfone, oxazoline or urethane. An independent claim is included for a kit for topical and/or internal uses on tissue in one or more separate containers, comprising polymerizable monomer adhesive composition and (I) comprising at least a component from oligomer and/or polymer flow retarding agent. ACTIVITY : Vulnerary. MECHANISM OF ACTION : None given.

Description

The The present invention relates to the use of a surface-modifying agent Composition for the preparation of a kit for topical and / or internal application to tissue, with the kit in one or more separate containers a polymerizable monomeric adhesive composition and a surface-modifying composition. The present invention also includes the kit as such.

State of the art

polymerizable Adhesive compositions based on cyanoacrylate have due to their easy to use and high curing speed and strength of the resulting adhesive bond is widely used found in both industrial and medical applications. It is known that monomeric forms of cyanoacrylates are extremely reactive and in the presence of even minute amounts of a polymerization initiator, including those contained in the air or on surfaces Polymerize existing moisture quickly. In doing so, the Initiation of polymerization by anions, free radicals, zwitterions or ion pairs. Once the polymerization has started is, the curing speed can be very large. Cyanoacrylate-based polymerizable adhesive compositions have therefore, for example, when joining plastics, Rubbers, glass, metals, wood and more recently also biological Tissues proved to be attractive solutions. medical Applications of cyanoacrylate adhesive compositions Both use as an alternative to or in addition to surgical sutures and staples when closing of wounds, as well as a use for covering and protecting surface wounds, such as lacerations, abrasions, Burns, stomatitis, inflammation and other open Surface wounds.

So be in the US Pat. Nos. 5,328,687 by Leung et al. 3,527,841 by Wicker et al., 3,722,599 by Robertson et al., 3,995,641 by Kronenthal et al. and 3,940,362 of Overhults, by way of example, discloses monomeric cyanoacrylates which are useful as surgical adhesives.

Across from the use of sutures or staples for the Wound care offers the alternative use of adhesive Cyanoacrylate based a number of advantages. Cause sutures in the immediate vicinity of the injury to be treated by the Penetration of the needle into the tissue and through the if necessary necessary administration of an anesthetic extra Injuries and are only put into a time-consuming procedure. The same applies to wound treatment using braces. This causes the use of these funds especially in pediatric cases is associated with problems, because they due to the impairments associated with them in the often very young patients strong anxiety and rejection reactions trigger.

By per se painless use of a cyanoacrylate-based wound adhesive according to any of Halpern in the U.S. Patent 3,667,472 or by Banitt et al. in the U.S. Patent 3,559,652 described above, the problems listed above can be at least partially circumvented or mitigated.

at the medical use of an adhesive composition Cyanoacrylate is usually applied in monomeric Shape. The directly on the tissue surface subsequent anionic in situ polymerization then leads to Wundverklebung or covering.

However, depending on the monomer used, the monomeric form of the adhesive composition tends to deliquesce readily at normal temperatures when applied to surfaces. As a result, the monomeric adhesive can spread into a wound or along a surface into areas that do not require an adhesive composition. Therefore, the viscosity of the polymerizable monomeric adhesive composition must be adjusted to prevent unnecessary leakage of the adhesive composition from a given area to which the adhesive is applied. In addition, sufficient time must be allowed for the monomeric materials to polymerize and thus provide the desired bonding effect. To achieve a sufficiently viscous adhesive, thickening agents may be added to the monomer compositions. Exemplary in this context are the U.S. Patents No. 3,527,841 for Wicker et al. and no. 5,665,817 for Greff et al. which each disclose the combination of a cyanoacrylate-based adhesive composition with thickeners for medical applications.

In addition to being viscous, cyanoacrylate based adhesive compositions should also be used Use in many medical applications to be sterile. Because of the importance of achieving and maintaining the sterility of these compositions, when an additive such as a thickening agent is added to an adhesive composition, it should be added prior to sterilization. As in the European patent EP-B1-1206291 However, certain thickeners require special pretreatment prior to addition to the polymerizable monomeric adhesive composition, or undergo a degradation or decomposition process under conditions of sterilization.

Some Thickener, such. As poly (2-octylcyanacrylat) decompose during Electron beam sterilization and sterilization by dry Heat. Thus, poly (2-octylcyanoacrylate is subject to a significant Degradation process when there is a dry sterilization cycle Heating at 160 ° C or electron beam irradiation exposed to 20-30 kGy.

Lots other thickeners also undergo decomposition under sterilization conditions. Such instability particularly often occurs in compositions in which the polymerizable monomeric adhesive composition stabilized by acids, as these acids often those also present in the composition Destabilize thickening polymers. So z. B. lactic acid-caprolactone copolymers in a stabilized 2-octyl cyanoacrylate monomer composition to decompose, if such a composition meets the conditions is subjected to sterilization by dry heating, which causes the thickener to have its thickening effect loses. However, such acid stabilizers are in many Cyanoacrylate adhesive compositions.

additionally for this, aseptic filtration is a known method for adhesive compositions cyanoacrylate-based before being placed in a container be sterilized. However, aseptic filtration is in compositions with high viscosity extremely difficult and is prohibitively expensive Technology connected. The control of the viscosity of a Adhesive composition without the addition of a thickener therefore seems due to the described problem especially in the medical field to be of high relevance.

In the application of medical adhesives has been found that in addition to the modification of the viscosity or the flow behavior of the polymerizable monomeric adhesive composition, the control of the rate of polymerization by the addition of additives is crucial. Too rapid polymerization can, as in the European patent EP-B1-1073484 by Narang et al. described cause due to the exothermic nature and the associated heat development to severe damage to the affected tissue. By the addition of various inhibitors, it is possible to achieve a reduction in the rate of polymerization, such as that in US Pat U.S. Patent 3,559,652 described Lewis acids (sulfur dioxide, nitrogen oxides, boron trifluoride and other substances).

The rate of polymerization is also reduced by the pretreatment of the wound site (tissue or wound fluids and thus moisture is removed from the area to be treated). This medically often required step of wound cleansing and disinfection can lead to an excessively slow polymerization of the adhesive composition unnecessarily delaying or hindering the treatment, which necessitates the addition of a polymerization initiator or promoter. For example, Dombroski et al. by doing U.S. Patent 4,042,442 the addition of a polymerization initiator (caffeine or theobromine) either by mixing the adhesive composition with the initiator immediately prior to use, or by spreading the initiator in a volatile solvent on the bond site. After evaporation of the solvent, the adhesive composition is applied and polymerization takes place.

One Disadvantage of the method presented by the authors lies in the Fact that they are only on technical tasks, such as the bonding described in the embodiments of metal-metal, metal-plastic or plastic-plastic surfaces is applicable. The use as a wound adhesive appears excluded because of the authors u. a. as possible solvents named chlorinated hydrocarbons, an application of the adhesive composition on tissue surfaces impossible.

by virtue of The problem described is therefore a need to develop a cyanoacrylate-based adhesive composition on the one hand, the flow behavior of the monomeric adhesive composition not exclusively by the addition of thickeners in the desired direction can be changed, so that the problems occurring during sterilization avoided can be. On the other hand, it is desirable the polymerization process on the tissue surface too control a medically required rate of polymerization to achieve without too high a thermal load of the associated tissue part.

task

Accordingly results for the present invention, the task when applying a polymerizable monomeric adhesive composition on a fabric surface both the polymerization process the monomeric adhesive composition to initiate and / or to accelerate and thereby an uncontrolled flow the polymerizable monomeric adhesive composition on the Prevent tissue surface.

Surprisingly has now been found to be through the use of a surface-modifying Composition for the preparation of a kit for topical and / or internal application to tissue both the polymerization of the monomers Adhesive composition initiated or the rate of polymerization could be accelerated and thereby a flow limitation reaches the adhesive composition on the tissue surface has been.

The Contains surface-modifying composition at least one component selected from the group the monomolecular, oligomeric and / or polymeric deletion retarder, this is suitable for the polymerization of a polymerizable monomer Initiate adhesive composition on the tissue surface and / or to accelerate and flow limitation of a monomeric polymerizable adhesive composition when applied to reach the tissue surface, the proportion of the respective Zerrorestadiermittels or mixtures thereof on the total amount of the surface-modifying composition 0.001-40 wt.% And each monomolecular, deliquescent, re-solidifying agent and / or at least 30% of the monomers of an oligomer and / or polymeric dissociation residual agent via at least one functional groups selected from ammonium, amide, amine, Anhydride, carbonyl, carboxylate, ethers, esters, hydroxyl, formamide, Imide, lactone, lactam, sulfone, oxazoline or urethane.

Under a flow limitation in the context of the invention is the reduction the running surface of a polymerizable monomeric adhesive composition when applied to a tissue surface by at least 1%, preferably at least 5%, more preferably at least 10%, most preferably by at least 15% and exceedingly preferably at least 20% compared to the running surface of a identical amount of the same polymerizable monomeric adhesive composition on an identical but untreated tissue surface to understand. The reduction of the running surface of a polymerizable monomeric adhesive composition when applied to a In particular, tissue surface may be even more pronounced and preferably at least 25%, at least 30%, at least 35%, at least 40%, at least 45% or at least 50% each on the running surface of an identical amount of the same polymerizable monomeric adhesive composition on an identical but untreated tissue surface amount.

Under a Zerlauffläche in the context of the invention is the surface to be understood by the polymerizable monomeric adhesive composition after application on a surface until training of the fully cured polymer film becomes. To a possible change of the Zerlauffläche being able to determine each will be an identical amount the same polymerizable monomeric adhesive composition each area of the test area of equal size or reference body distributed. The application is done of the polymerizable monomeric adhesive composition in comparison to their flow rate so fast that a different Flow behavior of the polymerizable monomeric adhesive composition on different surfaces during the Application can be neglected

The caused by the surface-modifying composition Flow limitation leads to a better localization the adhesive region and thus causes a reduction in the required Total amount of the polymerizable monomeric adhesive composition Based on cyanoacrylate and protects adjacent tissue regions from accidental contact with the adhesive.

In A preferred embodiment of the invention is the surface-modifying composition for the preparation a kit used in one or more separate containers a polymerizable monomeric adhesive composition and a Contains surface-modifying composition. In a first step, the surface-modifying Composition applied to the fabric surface and Subsequently, the application of the polymerizable monomeric adhesive composition.

By the application of the surface-modifying composition before application of the polymerizable monomeric adhesive composition there is an additional benefit. The surface-modifying Composition acts in the form of a layer and / or a polymeric Films as a thermal insulation matrix on the tissue surface and in this way reduces the on the underlying tissue part acting heat of polymerization. With that practice surface-modifying composition a protective function protects and preserves the tissue region to be treated from thermal damage Impairment while increasing ease of use for the patient. The initiation and / or acceleration the polymerization process by the surface-modifying Composition causes cyanoacrylate monomers to be used Although these are usually very good storage stabilities and have good film properties, due to their intrinsic properties slow rate of polymerization but usually no Find use.

Formel (I) Also preferred is the use of the surface-modifying composition for making a kit, wherein the polymerizable adhesive composition contains as a component a cyanoacrylate monomer according to formula (I) or a mixture of a cyanoacrylate monomer according to formula (I) with further cyanoacrylates, where R is a substituted or unsubstituted, straight-chain is branched or cyclic allyl, alkoxyalkyl, alkyl, alkenyl, haloalkyl or alkynyl group comprising 1 to 18 carbon atoms and / or includes an aromatic group or acyl group.

Formula (I)

preferred Embodiments include, without depending on them allyl-2-cyanoacrylate, beta-methoxy-ethyl-2-cyanoacrylate, methyl 2-cyanoacrylate, ethyl 2-cyanoacrylate, n-propyl 2-cyanoacrylate, iso-propyl 2-cyanoacrylate, n-butyl-2-cyanoacrylate, iso-butyl-2-cyanoacrylate (such as 1-butyl and 2-butyl), n-pentyl-2-cyanoacrylate, iso-pentyl-2-cyanoacrylate (as 1-pentyl, 2-pentyl and 3-pentyl), cyclopentyl-2-cyanoacrylate, n-hexyl-2-cyanoacrylate, iso-hexyl-2-cyanoacrylate (such as 1-hexyl, 2-hexyl, 3-hexyl and 4-hexyl), cyclohexyl-2-cyanoacrylate, n-heptyl-2-cyanoacrylate, iso-heptyl-2-cyanoacrylate (such as 1-heptyl, 2-heptyl, 3-heptyl and 4-heptyl), cycloheptyl-2-cyanoacrylate, n-octyl-2-cyanoacrylate, 2-octyl-2-cyanoacrylate, 3-octyl-2-cyanoacrylate, 4-octyl-2-cyanoacrylate decyl-2-cyanoacrylate, dodecyl-2-cyanoacrylate or lactoyl-2-cyanoacrylate, methoxy-isopropyl-2-cyanoacrylate, ethoxyethyl-2-cyanoacrylate, iso-propoxyethyl 2-cyanoacrylate and 2-butoxyethyl 2-cyanoacrylate and Combinations of said cyanoacrylates. As particularly preferred Exemplary embodiments are n-butyl-2-cyanoacrylate, n-octyl-2-cyanoacrylate and 2-octyl-2-cyanoacrylate.

regardless their inherent bacteriostatic effect, the polymerizable monomeric adhesive composition, preferably immediately after production and / or after packaging by a method selected by way of example from heat, ultrafiltration and irradiation or by a combination be sterilized the said methods.

In In another preferred embodiment, the invention surface-modifying composition for the preparation used in a kit, wherein the weight fraction of the monomolecular, oligomeric and / or polymeric flow-restirating agent, their mixtures at the Total amount of surface-modifying composition preferably 0.01-20%, more preferably 0.10-10%, most preferably 0.15-5% and most preferably 0.2-2.7%.

In Another preferred use of the surface modifying Composition contains this a monomolecular Zerrorestadiermittel, which is preferably selected from the group of the carboxylates, Hydroxides, sulfonates, stearates, pyrazines, amines, amides, acetates, Ammonium compounds, or nonionic surfactants or from their Mixtures. The monomolecular dissolution restorer is most preferred selected from 3,5-dibromopyridine, dialkylethanolamines and tribenzylamine or mixtures of said substances.

• a) Polyethylenimine.
• b) Polyvinyl- Homo- und Copolymere z. B. Polyvinylamin, Polyvinylpyrrolidon, Polyvinylcaprolactam, Polymethylvinylether, Polyvinylacetat bzw. Copolymere aus Poly(vinylpyrrolidon co vinylacetat), Poly(vinylpyrrolidon co vinylnonadecanoat) sowie Polymere mit alkyliertem Vinylpyrrolidon oder Copolymere in denen das Vinylacetat teilweise hydrolysiert ist.
• c) Polyacryl- und Polymethacryl-Homo-und Copolymere z. B. Polyacrylamide bzw. Copolymere aus Poly(dimethylaminopropylmethacrylamid co hydroxyethylmethacrylat).
• d) Copolymere aus Acryl- und Vinylverbindungen z. B. Poly(vinylpyrrolidon co alkylaminomethacrylat), Poly(vinylpyrrolidon co alkylaminoacrylamid), Poly(vinylpyrrolidon co acrylsäure co laurylmethacrylat) oder Poly(vinylcaprolactam co dimethylaminopropylmethacrylamid co hydroxyethylmethacrylat), Poly(methylvinylether co maleinsäureanhydrid).
• e) Copolymere mit anderen Doppelbindungen enthaltenden Monomeren z. B. Poly(isobutylen co ethylmaleimid co hydroxyethylmaleimid).
• f) Polysaccharide z. B. Cellulosederivate wie Hydroxyethylcellulose, Methylcellulose sowie gemischt substituierte Typen wie Methyl-Hydroxyethyl-Cellulose.
• g) Polyoxazoline, z. B. Polyethyloxazolin.
• h) Polyamidische Systeme wie Proteine oder Proteinhydrolysate, speziell solche die Cystein und/oder Lysin enthalten.
• i) Polyesteramide, wie Copolymere aus Adipinsäure mit Polyethern wie Polyethylenglykol und Aminen wie Ethylendiamin.
• j) Polyurethane bzw. Polyharnstoffe, z. B. aus TMXDI, MDI und Alkoholen (z. B. aus Polyether wie Polyethylenglykol, Polypropylenglykol, Polytetrahydrofuran) bzw. Aminen (z. B. aminterminierte Polyether).

In another preferred embodiment of the invention, the surface-modifying composition comprises an oligomeric and / or polymeric deletion retarder having a weight-average molecular weight of from 400 to 4,000,000 g / mol, which is preferably selected from the group of the following homo and copolymers or mixtures thereof, without themselves however, to limit to this:

• a) Polyethyleneimines.
• b) polyvinyl homo- and copolymers z. As polyvinylamine, polyvinylpyrrolidone, polyvinylcaprolactam, polymethylvinylether, polyvinyl acetate or copolymers of poly (vinylpyrrolidone co vinyl acetate), poly (vinylpyrrolidone co vinylnonadecanoat) and polymers with alkylated vinylpyrrolidone or copolymers in which the vinyl acetate is partially hydrolyzed.
• c) polyacrylic and polymethacrylic homo- and copolymers z. As polyacrylamides or copolymers of poly (dimethylaminopropylmethacrylamid co hydroxyethyl methacrylate).
• d) copolymers of acrylic and vinyl compounds z. As poly (vinylpyrrolidone co alkylaminomethacrylat), poly (vinylpyrrolidone co alkylaminoacrylamid), poly (vinylpyrrolidone co acrylic acid co laurylmethacrylat) or poly (vinylcaprolactam co dimethylaminopropylmethacrylamid co hydroxyethyl methacrylate), poly (methyl vinyl ether co maleic anhydride).
• e) copolymers with other double bond-containing monomers z. As poly (isobutylene co ethylmaleimid co hydroxyethylmaleimid).
• f) Polysaccharides z. As cellulose derivatives such as hydroxyethyl cellulose, methyl cellulose and mixed substituted types such as methyl hydroxyethyl cellulose.
• g) polyoxazolines, e.g. B. Polyethyloxazoline.
• h) polyamide systems such as proteins or protein hydrolysates, especially those containing cysteine and / or lysine.
• i) polyesteramides such as copolymers of adipic acid with polyethers such as polyethylene glycol and amines such as ethylenediamine.
• j) polyurethanes or polyureas, for. From TMXDI, MDI and alcohols (eg from polyethers such as polyethylene glycol, polypropylene glycol, polytetrahydrofuran) or amines (eg amine-terminated polyethers).

The Topology of Oligomeric and / or Polymeric Degradation Retarders may preferably be linear, branched and / or star-shaped. Block copolymers are possible and offer z. B. at Graftpolymerisation of vinyl compounds on polyurethanes.

The oligomeric and / or polymeric according to the invention Discharge restoratives may preferably also be ionic, bear quaternary groups. As examples are in this In connection with, but not limited to, the halide salts of the copolymer poly (vinylpyrrolidone co dimethylaminopropylmethacrylamide co methacryloylaminopropyllauryldimethylammonium) or the alkali metal salts of the copolymer poly (methyl vinyl ether co maleisäurebutylethylester) called.

The Use of an oligomeric and / or polymeric flow-restoring agent as a surface-modifying composition before application a polymerizable monomeric adhesive composition is included Wound care is associated with a number of benefits. Next the already mentioned flow limitation, polymerization initiation and protective effect as a thermal insulation matrix acts the oligomeric and / or polymeric film on the fabric surface as additional antimicrobial barrier. In the case of cyanoacrylate wound adhesives, it is known that the formed cyanoacrylate polymer film becomes brittle after a few days and can be cracked, which causes the affected Tissue part no longer optimally protected against environmental influences is. A germ-free and water-repellent covering of the wound region can be difficult in such cases. By the application of the oligomeric and / or polymeric Zerrorestadiermittels becomes an additional flexible and elastic polymer film anchored to the tissue surface, which causes that in addition to a better cohesion of the wound an additional Barrier the affected tissue region from the entry of pathogens and protects germs from the outside.

In a particularly preferred use of the surface-modifying Composition contains this as another component organic alcohol, mixtures of various organic alcohols or mixtures of one or more organic alcohols with water, wherein the proportion by weight of the organic alcohol, the mixtures various organic alcohols or mixtures of one or more Organic alcohols with water based on the total amount of at least 60% of the surface-modifying composition, preferably at least 80%, more preferably at least 90% and completely more preferably at least 95%.

Preferably the organic alcohol is selected from ethanol, n-propanol, i-propanol, n-butanol, 2-butanol, i-butanol, 1,3-butanediol, Phenoxyethanol, 1,2-propylene glycol and glycerol and mixtures the genanten alcohols.

In a further particularly preferred embodiment of the invention, the surface-modifying composition contains a monomolecular, oligomeric or polymeric deliquescent or a mixture of said Zerrorestadiermittel, wherein the respective Zerrorestadiermittel or the mixture of different Zerrorestadiermittel in the organic alcohol, in the mixture of different organic alcohols or in the mixture of one or more organic alcohols dispersed with water and / or dissolved.

In a further use of the invention surface-modifying composition is this preferably in the form of a liquid, as a gel, as a suspension or as a paste before.

In another preferred form of surface modifying Composition for making a kit contains these Kit in at least one container additionally at least another component selected from the groups of antimicrobial agents, the plasticizer, the thickener, stabilizers, skin-care active ingredients, perfumes, the healing agent, the coloring substances, the indicator dyes, the heat-dissipating reagents and / or the anti-inflammatory Means is included.

invention Antimicrobial agents are preferably in an amount of usually 0.0001 to 3 wt .-%, preferably 0.0001 to 2 wt .-%, in particular 0.0002 to 1 wt .-%, particularly preferably 0.0002 to 0.2 wt .-%, extremely preferably 0.0003 to 0.1 wt .-%, each based on the total amount the polymerizable monomeric adhesive composition.

antimicrobial Active substances are differentiated depending on the antimicrobial spectrum and Mechanism of action between bacteriostats and bactericides, fungistatics and fungicides. Important substances from these groups are, for example Benzalkonium chlorides, alkylaryl sulfonates, halophenols and phenol mercuriacetate. The terms antimicrobial action and antimicrobial agent have in the context of the teaching of the invention usual meaning. Suitable antimicrobial agents are preferably selected from the groups of the alcohols, Amines, aldehydes, antimicrobial acids or their salts, Carboxylic acid esters, acid amides, phenols, phenol derivatives, Diphenyls, diphenylalkanes, urea derivatives, oxygen, nitrogen acetals and -formals, benzamidines, isothiazolines, phthalimide derivatives, Pyridine derivatives, antimicrobial surface-active compounds, Guanidines, antimicrobial amphoteric compounds, quinolines, 1,2-dibromo-2,4-di-cyanobutane, iodo-2-propyl-butyl-carbamate, iodine, Iodine-polymer complexes, iodophores, peroxo compounds, halogen compounds and any mixtures of the preceding.

The antimicrobial agent is preferably selected from undecylenic acid, benzoic acid, salicylic acid, dihydracetic acid, o-phenylphenol, N-methylmorpholine-acetonitrile (MMA), iodine-PVP complexes, 2-benzyl-4-chlorophenol, 2,2'-methylene-bis- (6-bromo-4-chlorophenol), 4,4'-di-chloro-2'-hydroxydiphenyl ether (Dichlosan), 2,4,4'-trichloro-2'-hydroxydiphenyl ether (trichlosan), chlorhexidine, N- (4 -Chlorophenyl) -N- (3,4-dichlorophenyl) -urea, N, N '- (1,10-decanediyldi-1-pyridinyl-4-ylidene) bis (1-octanamine) dihydrochloride, N , N'-bis (4-chlorophenyl) -3,12-diimino-2,4,11,13-tetraaza-tetradecandiimidamide, glucoprotamines, antimicrobial quaternary surface active compounds, guanidines including the bi- and polyguanidine, such as 1 , 6-bis- (2-ethylhexyl-biguanido-hexane) -dihydrochloride, 1,6-di (N1, N1'-phenyldiguanido-N5, N5 ') - hexane-tetrahydrochloride, 1,6-di- (N1, N1'-phenyl-N1, N1 -methyldiguanido-N5, N5 ') - hexane-dihydrochloride, 1,6-di- (N1, N1'-o-chlorophenyldiguanido-N5, N5') - hexane-di hydrochloride, 1,6-di- (N1, N1'-2,6-dichlorophenyldiguanido-N5, N5 ') hexane dihydrochloride, 1,6-di- [N1, N1'-beta- (p-methoxyphenyl) diguanido- N5, N5 '] - hexanedihydrochloride, 1,6-di- (N1, N1'-alpha-methyl-beta.-phenyldiguanido-N5, N5') - hexane dihydrochloride, 1,6-di - (N1, N1'-p-nitrophenyldiguanido-N5, N5 ') hexane dihydrochloride, omega: omega-di- (N1, N1'-phenyldiguanido-N5, N5') - di-n-propyl ether dihydrochloride, omega: omega'-di- (N1, N1'-p-chlorophenyldiguanido-N5, N5 ') - di-n-propyl ether tetrahydrochloride, 1,6-di- (N1, N1'-2,4-dichlorophenyldiguanido-N5, N5 ') hexane-tetrahydrochloride, 1,6-di- (N1, N1'-p-methylphenyldiguanido-N5, N5') hexane dihydrochloride, 1,6-di- (N1, N1'-2,4,5-trichlorophenyldiguanido -N5, N5 ') hexane-tetrahydrochloride, 1,6-di- [N1, N1'-alpha (p-chlorophenyl) ethyldiguanido-N5, N5'] hexane dihydrochloride, omega: omega-di- (N1, N1 '-p-chlorophenyldiguanido-N5, N5') m-xylenedihydrochloride, 1,12-di (N1, N1'-p-chlorophenyldiguanido-N5, N5 ') dodecane dihydrochloride, 1,10-di (N1 , N 1 -phenyldiguanido-N5, N5 ') - decantetrahydrochlorid 1,12-di- (N1, N1'-phenyldiguanido-N5, N5 ') dodecane-tetrahydrochloride, 1,6-di- (N1, N1'-o-chlorophenyl-guanido-N5, N5') hexane-dihydrochloride , 1,6-di- (N1, N1'-o-chlorophenyldiguanido-N5, N5 ') hexane-tetrahydrochloride, ethylene-bis (1-tolyl-biguanide), ethylene-bis (p-tolyl-biguanide), Ethylene bis (3,5-dimethylphenylbiguanide), ethylene bis (p-tert-amylphenylbiguanide), ethylene bis (nonylphenylbiguanide), ethylene bis (phenylbiguanide), ethylene bis (N-butylphenylbiguanide), Ethylene bis (2,5-diethoxyphenylbiguanide), ethylene bis (2,4-dimethylphenylbiguanide), ethylene bis (o-diphenylbiguanide), ethylene bis (mixed amyl naphthyl biguanide), N-butyl ethylene bis (phenylbiguanide), trimethylene-bis- (o-tolylbiguanide), N-butyl-trimethyl-bis- (phenylbiguanide) and the corresponding salts such as acetates, gluconates, hydrochlorides, hydrobromides, citrates, bisulfites, fluorides, polymaleates, N- Cocosalkylsarcosinate, Phosphites, hypophosphites, perfluorooctanoates, silicates, sorbates, salicylates, maleates, tartrates, fumarates, ethylenediaminetetraacetates, iminodiacetates, cinnamates, thiocyanates, arginates, pyromellitates, tetracarboxybutyrates, benzoates, glutarates, monofluorophosphates, perfluoropropionates and any mixtures thereof. Furthermore, halogenated xylene and cresol derivatives, such as p-chloromethacresol or p-chlorometaxylene, as well as natural antimicrobial agents of plant origin (eg from spices or herbs), of animal and microbial origin are suitable. Preferably, antimicrobial surface-active quaternary compounds, a natural antimicrobial agent of plant origin and / or a natural antimicrobial agent of animal origin, most preferably at least one natural antimicrobial agent of plant origin from the group comprising caffeine, theobromine and theophylline and essential oils such as eugenol, thymol and geraniol, and / or at least one natural antimicrobial agent of animal origin from the group, comprising enzymes such as protein from milk, lysozyme and lactoperoxidase, and / or at least one antimicrobial surface-active quaternary compound with an ammonium, sulfonium, phosphonium, iodonium - or Arsoniumgruppe, peroxo compounds and chlorine compounds are used. Also substances of microbial origin, so-called bacteriocins, can be used. Glycine, glycine derivatives, formaldehyde, compounds which readily split off formaldehyde, formic acid and peroxides are preferably used.

When Antimicrobial agents are also particularly quaternary Ammonium compounds (QAV) are preferred. The quaternary ammonium compounds (QAV) have the general formula (R1) (R2) (R3) (R4) N + X-, in the R1 to R4 identical or different C1-C22-alkyl radicals, C7-C28-aralkyl radicals or heterocyclic radicals, where two or in the case of an aromatic Integration as in pyridine even three radicals together with the nitrogen atom the heterocycle, for example a pyridinium or imidazolinium compound, form, represent and X-halide ions, sulfate ions, Hydroxide ions or similar anions are. For Optimal antimicrobial activity is preferably at least one of the radicals has a chain length of 8 to 18, in particular 12 to 16, C atoms on.

QAC are by reaction of tertiary amines with alkylating agents, such as methyl chloride, benzyl chloride, dimethyl sulfate, dodecyl bromide, but also ethylene oxide produced. The alkylation of tertiary amines with a long alkyl radical and two methyl groups succeeds especially easy, also the quaternization of tertiary amines with Two long residues and one methyl group can be added with the help of methyl chloride mild conditions are carried out. Amines, over have three long alkyl radicals or hydroxy-substituted alkyl radicals, are less reactive and are preferably quaternized with dimethyl sulfate.

suitable QAC are, for example, benzalkonium chloride (N-alkyl-N, N-dimethylbenzylammonium chloride, CAS No. 8001-54-5), benzalkone B (m, p-dichlorobenzyl-dimethyl-C 12 -alkylammonium chloride, CAS No. 58390-78-6), benzoxonium chloride (benzyldodecyl-bis (2-hydroxyethyl) ammonium chloride), Cetrimonium bromide (N-hexadecyl-N, N-trimethylammonium bromide, CAS No. 57-09-0), benzetonium chloride (N, N-dimethyl-N- [2- [2- [p- (1,1,3,3-tetramethylbutyl) phenoxy] ethoxy] ethyl] benzyl ammonium chloride, CAS No. 121-54-0), dialkyldimethylammonium chlorides such as di-n-decyl-dimethyl-ammonium chloride (CAS No. 7173-51-5-5), didecyldi-methylammonium bromide (CAS No. 2390-68-3), Dioctyldimethylammonium chloride 1-cetylpyridinium chloride (CAS no. 123-03-5) and thiazoline iodide (CAS No. 15764-48-1) and mixtures thereof. Particularly preferred QACs are the benzalkonium chlorides with C 8 -C 18 -alkyl radicals, in particular C12-C14-alkyl-benzyl-dimethyl-ammonium chloride.

Benzalkonium halides and / or substituted benzalkonium halides are for example commercially available as Barquat ^® ex Lonza, Marquat® ^® ex Mason, Variquat ^® ex Witco / Sherex and Hyamine ^® ex Lonza and as Bardac ^® ex Lonza. Other commercially obtainable antimicrobial agents are N- (3-chloroallyl) hexaminium chloride such as Dowicide and Dowicil ^{® ®} ex Dow, benzethonium chloride such as Hyamine ^® 1622 ex Rohm & Haas, methylbenzethonium as Hyamine ^® 10X ex Rohm & Haas, cetylpyridinium chloride such as Cepacol ex Merrell Labs ,

Provided in a preferred embodiment of the invention Plasticizer, this gives the formed from the monomer Polymer flexibility and preferably contains little or no moisture and should the stability or not significantly affect the polymerization of the monomer. Such plasticizers are useful in polymerized compositions, for closing or covering wounds, cuts, Abrasions, inflammation or other applications to be used in which flexibility of the adhesive is desirable.

Particularly suitable plasticizers are triaryl or trialkyl phosphates and ester compounds. The alcohol component of the ester is preferably alcohols with 1 to 5, in particular with 2 to 4 OH groups and with up to 2 to 5, in particular 3 or 4 directly interconnected carbon atoms. The number of not directly connected C atoms can be up to 110, in particular up to 18 carbon atoms.

When Monohydric alcohols are suitable for the following substances: 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-buten-2-ol, 3-methyl-3-buten-2-ol, 1-cyclopropyl-ethanol, 1-penten-3-ol, 3-penten-2-ol, 4-penten-1-ol, 4-penten-2-ol, 3-pentin-1-ol, 4-Pentin-1-ol, propargyl alcohol, allyl alcohol, hydroxyacetone, 2-methyl-3-butyn-2-ol.

When Divalent alcohols are for example: 1,2-ethanediol, 1,2-propanediol, 1,3-propanediol, dihydroxyacetone, thioglycerol, 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-buten-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-cyclopentene-1,3-diol, 2-methylene-1,3-propanediol, 2,3-Dihydroxy-1,4-dioxane, 2,5-dihydroxy-1,4-dithiane.

The following Trivalent alcohols can be used: glycerol, Erythrulose, 1,2,4-butanetriol, erythrose, threose, trimethylolethane, Trimethylolpropane and 2-hydroxymethyl-1,3-propanediol.

From The tetrahydric alcohols may, for example, be erythritol, Threit, pentaerythritol, arabinose, ribose, xylose, ribulose, xylulose, Lyxose, ascorbic acid, glucono-γ-lactone be used.

When Examples of pentahydric alcohols may be mentioned: Arabitol, adonite, xylitol. Other suitable monohydric or polyhydric alcohols are familiar to the expert.

The For example, polyhydric alcohols described above can be used also be used in the form of ethers. The ethers can for example by condensation reactions, Williamson's ether synthesis or by reaction with alkylene oxides such as ethylene, propylene or Butylene oxide can be prepared from the abovementioned alcohols. Examples include: diethylene glycol, triethylene glycol, Polyethylene glycol, diglycerol, triglycerol, tetraglycerol, pentaglycerol, Polyglycerol, technical mixtures of the condensation products of Glycerine, glycerol propoxylate, diplycerol propoxylate, pentaerythritol ethoxylate, Dipentaerythritol, ethylene glycol monobutyl ether, propylene glycol monohexyl ether, Butyl diglycol, dipropylene glycol monomethyl ether.

When Monovalent carboxylic acids for esterification with For example, the above-mentioned alcohols can be used 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-methyl-2-oxo-butyric acid, propiolic acid, tetrahydrofuran-2-carboxylic acid, Methoxyacetic acid, dimethoxyacetic acid, 2- (2-methoxyethoxy) -acetic acid, Pyruvic acid, 2-methoxyethanol, vinylacetic acid, Allylacetic acid, 2-pentenoic acid, 3-pentenoic acid.

When Examples of polybasic carboxylic acids may be mentioned: Oxalic acid, malonic acid, fumaric acid, maleic acid, Succinic acid, glutaric acid, acetylenedicarboxylic acid, Oxaloacetic acid, acetonedicarboxylic acid, mesoxalic acid, Citraconic acid, dimethylmalonic acid, methylmalonic acid, Ethylmalonic. Also hydroxycarboxylic acids can be used as starting materials, for. Tartronic acid, Lactic acid, malic acid, tartaric acid, citramalic acid, 2-hydroxyvaleric acid, 3-hydroxyvaleric acid, 3-hydroxybutyric acid, 3-hydroxyglutaric acid, dihydroxyfumaric acid, 2,2-dimethyl-3-hydroxypropionic acid, dimethylolpropionic acid, Glycolic acid, citric acid.

The esterification can be either complete or partial. Optionally, mixtures of these acids can be used for the esterification. The esters prepared from these 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 can be distilled. Examples of esters which are particularly suitable as plasticizers are: ethyl acetate, butyl acetate, glycerol triacetate, glycerol tripropionate, triglycerol pentaacetate, polyglycerol acetate, diethylene glycol diacetate, 3-hydroxyvaleran acid ethyl ester, butyl lactate, Milchsäureisobutylester, 3-hydroxybutyric acid ethyl ester, diethyl oxalate, Mesoxalsäurediethylester, Äpfelsäuredimethylester, Apfelsäurediisopropylester, diethyl tartrate, Weinsäuredipropylester, diisopropyl tartrate, dimethyl glutarate, dimethyl succinate, diethyl succinate, diethyl maleate, diethyl fumarate, diethyl malonate, acrylic acid 2-hydroxyethyl, 3-oxovalerate, glycerol diacetate, glycerol tributyrate, glycerol tripropionate, Glycerindipropionat, Glycerintriisobutyrat, Glycerindiisobutyrat, glycidyl butyrate, Acetessigsäurebutylester, ethyl levulinate, 3-Hydroxyglutarsäuredimethylester, Glycerinacetatdipropionat, Glycerindiacetatbutyrat, propionate, propylene glycol diacetate, Propylenglykoldibutyrat, Diethylenglykoldibutyrat, Trimethylolethantriacetat, trimethylolpropane triacetate, Trimethylolethantributyrat, Neopentylalkoholdibuty rat, methoxyacetic acid pentyl ester, butyl dimethoxyacetate, butyl glycolate.

The mentioned esters may be present in an amount of up to 50% by weight, preferably in an amount of 0.5 to 30 wt .-%, more preferably be added in an amount of 1 to 20 wt .-%, based on the Total amount of the polymerizable monomeric adhesive composition.

Further suitable plasticizers are, for example, esters, such as abietic acid esters, Adipic acid ester, azelaic acid ester, benzoic acid ester, Butyric acid ester, acetic ester, ester higher Fatty acids containing from about 8 to about 44 carbon atoms, ester OH groups pregnant or epoxidized fatty acids, fatty acid esters and fats, glycolic esters, phosphoric esters, Phthalic acid esters, containing from 1 to 12 carbon atoms linear or branched alcohols, propionic acid esters, sebacic acid esters, Sulfonic acid esters, thiobutyric acid esters, trimellitic esters, Citric acid esters, as well as mixtures of two or more thereof. Particularly suitable are the asymmetric esters of difunctional, aliphatic or aromatic dicarboxylic acids, for example the esterification product of adipic acid monooctyl ester with 2-ethylhexanol (Edenol DOA, Cognis, Dusseldorf) or the esterification product of phthalic acid with butanol.

linear or branched polyesters with polymerized phthalic acid, Isophthalic acid and / or adipic acid are plasticizers as well as the pure or mixed monofunctional ethers, linear or branched C4-16 alcohols or mixtures of two or more different ethers of such alcohols, for example Dioctyl ether (available as Cetiol OE, Cognis, Dusseldorf).

Furthermore are suitable as plasticizers end-capped polyethylene glycols. For example, polyethylene or polypropylene glycol di-C1-4 alkyl ethers, in particular the dimethyl or diethyl ether of diethylene glycol or dipropylene glycol, as well as mixtures of two or more thereof. Particularly preferred plasticizers are tributyl citrate, triaryl phosphate and acetyltributyl citrate.

optional can in a preferred embodiment of the Invention polymers are added, for. For example, the viscosity to increase or to vary the adhesive properties. These additives serve as thickeners and influence the Rheology of the adhesive mixture in the desired manner. The polymers may be present in an amount of 1 to 60, especially 10 to 50, preferably 10 to 30 wt .-% based on the total formulation be used. Particularly suitable are polymers based on Vinyl ethers, vinyl esters, esters of acrylic acid and methacrylic acid with 1 to 22 carbon atoms in the alcohol component, styrene or thereof derived co- and terpolymers with ethene, butadiene. Preferred are Vinyl chloride / vinyl acetate copolymers with a vinyl chloride content from 50 to 95% by weight. The polymers can be in liquid, resinous or in solid form. Particularly important is that the polymers are not contaminants from the polymerization process contain the curing of the adhesive composition inhibit on cyanoacrylate basis. If the polymers are too high Have water content, must be dried if necessary.

The Molecular weight may be scattered in a wide range at least at Mw = 1.5 kg / mol, but not more than 1,000 kg / mol, because otherwise the final viscosity of the adhesive formulation is too high. It can also be mixtures of the above Polymers are used. In particular, the combination of low and high molecular weight products has particular advantages in terms of the final viscosity of the adhesive formulation. As examples for suitable polymers based on vinyl acetate may be mentioned: the Mowilith types 20, 30, and 60, the Vinnapas types B1,5, B100, B17, B5, B500 / 20VL, 660, UW10, UW1, UW30, UW4 and UW50. As examples for suitable polymers based on acrylate may be mentioned: Acronal 4F and Laromer types 8912, PE55F and PO33F. As examples for suitable polymers based on methacrylate may be mentioned: Elvacite 2042, the Neocryl types B 724, B999 731, B 735, B 811, B 813, B 817 and B722, the Plexidon MW 134, the Plexigum types M 825, M 527, N 742, N 80, P 24, P 28 and PQ 610. As an example of suitable polymers based on vinyl ethers may be mentioned: Lutonal A25. For thickening also cellulose derivatives and silica gel be used. Particularly noteworthy is the addition of polycyanoacrylates.

generally known For example, cyanoacrylates are susceptible to both anionic and free radical polymerization. It is therefore advisable to use the ester masses against both types of polymerization protect against premature hardening of the Esters done, thereby avoiding difficulties in storage become. These inhibitors thus cause the setting behavior over a significantly extended storage time is not significant changed. In other words, is used by the one or more Inhibitors a spontaneous or slow polymerization quantitatively prevented. Furthermore, discoloration of the adhesive is at prevents storage.

Around can prevent anionic polymerization, in a preferred embodiment of the invention anionic Polymerization inhibitors are added. Suitable for this are all anionic polymerization inhibitors that were previously on used in the field of cyanoacrylic ester adhesives have been. For example, the anionic polymerization inhibitor an acid gas, a protonic acid or an anhydride be of it. The preferred anionic polymerization inhibitor for the adhesives according to the invention is sulfur dioxide or boron trifluoride, preferably in an amount of 0.0001 to 5 Wt .-%, more preferably in an amount of 0.0005 to 1 wt .-% and most preferably in an amount of 0.001 to 0.5 wt .-% based on the total amount of polymerizable monomeric adhesive composition. Further usable anionic polymerization inhibitors are nitrous oxide, Hydrogen fluoride, hydrochloric acid, sulfuric acid, Phosphoric acid, organic sulfonic and carboxylic acids and anhydrides thereof, phosphorus pentoxide and acid chlorides. The adhesives according to the invention may also be a radical polymerization inhibitor be added in an amount of 0.01 to 0.05 wt .-%. This radical polymerization inhibitor may be one of the polymerizable monomeric adhesive compositions cyanoacrylate-based radical polymerization inhibitors be. Usually, phenolic compounds, for example Hydroquinone, butylated hydroxyanisole (BHA), 2,6-di-tert-butyl-4-methylphenol (BHT), t-butyl catechinone, catechol and p-methoxyphenol used.

In Another preferred use of the surface modifying Composition for making a kit may be one or contain several skin-care active ingredients. Skin care active ingredients In particular, such agents may be those of the skin give a sensory advantage, z. B. by lipids and / or Moisturizing factors and thus the healing of the support affected tissue.

• a) Wachse wie beispielsweise Carnauba, Spermaceti, Bienenwachs, Lanolin und/oder Derivate derselben und andere.
• b) Hydrophobe Pflanzenextrakte
• c) Kohlenwasserstoffe wie beispielsweise Squalene und/oder Squalane
• d) Höhere Fettsäuren, vorzugsweise solche mit wenigstens 12 Kohlenstoffatomen, beispielsweise Laurinsäure, Stearinsäure, Behensäure, Myristinsäure, Palmitinsäure, Ölsäure, Linolsäure, Linolensäure, Isostearinsäure und/oder mehrfach ungesättigte Fettsäuren und andere.
• e) Höhere Fettalkohole, vorzugsweise solche mit wenigstens 12 Kohlenstoffatomen, beispielsweise Laurylalkohol, Cetylalkohol, Stearylalkohol, Oleylalkohol, Behenylalkohol, Cholesterol und/oder 2-Hexadecanaol und andere.
• f) Ester, vorzugsweise solche wie Cetyloctanoate, Lauryllactate, Myristyllactate, Cetyllactate, Isopropylmyristate, Myristylmyristate, Isopropylpalmitate, Isopropyladipate, Butylstearate, Decyloleate, Cholesterolisostearate, Glycerolmonostearate, Glyceroldistearate, Glyceroltristearate, Alkyllactate, Alkylcitrate und/oder Alkyltartrate und andere.
• g) Lipide wie beispielsweise Cholesterol, Ceramide und/oder Saccharoseester und andere.
• h) Vitamine wie beispielsweise die Vitamine A und E, Vitaminalkylester, einschließlich Vitamin C Alkylester und andere.
• i) Sonnenschutzmittel
• j) Phospholipide
• k) Derivate von alpha-Hydroxysäuren
• l) Germizide für den kosmetischen Gebrauch, sowohl synthetische wie beispielsweise Salicylsäure und/oder andere als auch natürliche wie beispielsweise Neemöl und/oder andere.
• m) Silikone

Skin-care active substances are known to the person skilled in the art and can preferably be selected from the following substance groups or from mixtures of the following substance groups, without, however, being restricted to these:

• a) waxes such as carnauba, spermaceti, beeswax, lanolin and / or derivatives thereof and others.
• b) Hydrophobic plant extracts
• c) hydrocarbons such as squalene and / or squalane
• d) Higher fatty acids, preferably those having at least 12 carbon atoms, for example lauric acid, stearic acid, behenic acid, myristic acid, palmitic acid, oleic acid, linoleic acid, linolenic acid, isostearic acid and / or polyunsaturated fatty acids and others.
• e) Higher fatty alcohols, preferably those having at least 12 carbon atoms, for example, lauryl alcohol, cetyl alcohol, stearyl alcohol, oleyl alcohol, behenyl alcohol, cholesterol and / or 2-hexadecanol and others.
• f) esters, preferably such as cetyloctanoates, lauryl lactates, myristyl lactates, cetyl lactates, isopropyl myristates, myristyl myristates, isopropyl palmitates, isopropyl adipates, butyl stearates, decyl oleates, cholesterol stearates, glycerol monostearates, glycerol distearates, glycerol tristearates, alkyl lactates, alkyl citrates and / or alkyl tartrates and others.
• g) lipids such as cholesterol, ceramides and / or sucrose esters and others.
• h) vitamins such as vitamins A and E, vitamin C esters, including vitamin C alkyl esters and others.
• i) sunscreen
• j) phospholipids
• k) derivatives of alpha hydroxy acids
• l) Germicides for cosmetic use, both synthetic and, for example, salicylic acid and / or others as well as natural ones such as neem oil and / or others.
• m) silicones

In a further preferred embodiment, the kit contains perfume as further component. Suitable perfumes are known to the person skilled in the art. The following are some examples of perfumes but without being limited to them.

With the term perfume are perfume oils, aroma, Meant fragrances and fragrances. As perfume oils are called Mixtures of natural and synthetic fragrances.

natural Fragrances are extracts of flowers (lily, lavender, Roses, jasmine, neroli, ylang-ylang), stems and leaves (Geranium, patchouli, petitgrain), fruits (anise, coriander, Caraway, juniper), fruit peel (bergamot, lemon, Oranges), roots (macis, angelics, celery, cardamom, costus, Iris, Calmus), wood (pine, sandal, guaiac, cedar, Rosewood), herbs and grasses (tarragon, lemongrass, Sage, thyme, chamomile), needles and twigs (spruce, fir, pine, Pines), resins and balms (galbanum, elemi, benzoin, myrrh, Olibanum, Opoponax).

Farther come from animal raw materials, such as civet and Castoreum.

typical synthetic fragrance compounds are products of the ester type, Ethers, aldehydes, ketones, alcohols and hydrocarbons. fragrance compounds the type of ester are z. Benzyl acetate, phenoxyethyl isobutyrate, p-tert-butylcyclohexyl acetate, linalyl acetate, dimethylbenzylcarbinyl acetate, Phenylethyl acetate, linalyl benzoate, benzyl formate, ethylmethylphenyl glycinate, Allylcyclohexylpropionate, styrallylpropionate, cyclohexylsalicylate, Floramat, Melusat, Jasmecyclat and Benzylsalicylat. To the Ethern For example, benzyl ethyl ether and ambroxane include the aldehydes z. B. the linear alkanals having 8 to 18 carbon atoms, Citral, citronellal, citronellyloxyacetaldehyde, cyclamenaldehyde, Hydroxycitronellal, Lilial and Bourgeonal, to the ketones z. B. the Jonone, α-isomethylionone and Methylcedrylketon, too the alcohols anethole, citronellol, eugenol, isoeugenol, geraniol, Linalool, phenylethyl alcohol and terpineol, to the hydrocarbons mainly include the terpenes and balms like limes and pinas.

Prefers However, mixtures of different fragrances are used, the together create an appealing scent. Also essential oils lower volatility, which is mostly used as aroma components are suitable as perfume oils, z. Sage oil, Chamomile oil, clove oil, lemon balm oil, mint oil, Cinnamon leaf oil, lime blossom oil, Juniper Berry Oil, Vetiver Oil, Oliban Oil, Galbanum oil, labolanum oil and lavandin oil. Preferably Bergamot oil, Dihydromyrcenol, Lilial, Lyral, Citronellol, Phenylethyl alcohol, α-hexyl cinnamaldehyde, geraniol, benzylacetone, Cyclamenaldehyde, Linalool, Boisambrene Forte, Ambroxan, Indole, Hedione, Sandelice, lemon oil, tangerine oil, orange blossom oil, Orange Peel Oil, Sandalwood Oil, Neroliol Allylamyl Glycolate, Cyclovertal, Lavandin oil, Muscat sage oil, β-Damascone, Geranium oil Bourbon, cyclohexyl salicylate, Vertofix Coeur, Iso-E-Super, Fixolide NP, Evernyl, Iraldeine gamma, Phenylacetic acid, Geranyl acetate, benzyl acetate, rose oxide, romilllate, irotyl and floramate used alone or in mixtures.

Further examples of fragrances which may be present in the compositions according to the invention are found, for example, in US Pat. In S. Arctander, Perfume and Flavor Materials, Vol. I and II, Montclair, NJ, 1969, self-published or K. Bauer, D. Garbe and H. Surburg, Common Fragrance and Flavor Materials, 3rd. Ed., Wiley-VCH, Weinheim 1997 ,

Around to be perceptible, a perfume must be volatile, besides the nature of the functional groups and the structure the molecular weight of the chemical compound also plays an important role plays. So most perfumes have molecular weights up to about 200 Dalton, while molar masses of 300 Daltons and above tend to be constitute an exception. Due to the different volatility of fragrances, the smell of one of several changes Fragrances of composite perfume or fragrance during evaporation, taking the odor impressions in "top note", "heart or middle note" (middle note or body) and "base note" (end note or dry out). Because the smell perception to a large Part also based on the odor intensity, there is the Top note of a perfume or fragrance not only from volatile Compounds, while the base note to the largest Part of less volatile, d. H. adherent fragrances consists.

Adhesive-resistant fragrances which are advantageously usable in the context of the present invention are, for example, the essential oils such as angelica root oil, aniseed oil, Arnica blossom oil, basil oil, bay oil, bergamot oil, Champacablütenöl, Edeltannenöl, Edeltannenzapfenapfen, Elemiöl, eucalyptus oil, fennel oil, spruce oil, galbanum oil, geranium oil, gingergrass oil , Guaiac wood oil, gurdy balm oil, helichrysum oil, ho oil, ginger oil, iris oil, cajeput oil, calamus oil, chamomile oil, camphor oil, kanaga oil, cardamom oil, cassia oil, pine needle oil, copaϊva balsam oil, coriander oil, spearmint oil, cumin oil, cumin oil, lavender oil, lemongrass oil, lime oil, tangerine oil, lemon balm oil , Musk Grain Oil, Myrrh Oil, Clove Oil, Neroli Oil, Niaouli Oil, Olibanum Oil, Orange Oil, Origanum Oil, Palmarosa Oil, Patchouli Oil, Peru Balsam Oil, Petitgrain Oil, Pepper Oil, Peppermint Oil, Pimento Oil, Pine Oil, Rose oil, rosemary oil, sandalwood oil, celery oil, spiked oil, star aniseed oil, turpentine oil, thuja oil, thyme oil, verbena oil, vetiver oil, juniper berry oil, wormwood oil, wintergreen oil, ylang-ylang oil, hyssop oil, cinnamon oil, cinnamon leaf oil, citron oil, lemon oil and cypress oil.

But also the higher-boiling or solid fragrances natural or of synthetic origin may be within the scope of the present invention Invention advantageously as adherent fragrances or fragrance mixtures, So fragrances are used. These connections include the following compounds as well as mixtures of these: Ambrettolide, amyl cinnamic aldehyde, anethole, anisaldehyde, aniseed alcohol, Anisole, methyl anthranilate, acetophenone, benzylacetone, Benzaldehyde, ethyl benzoate, benzophenone, benzyl alcohol, Benzyl acetate, benzyl benzoate, benzyl formate, benzyl valerate, borneol, Bornyl acetate, bromostyrene, n-decyl aldehyde, n-dodecyl aldehyde, eugenol, Eugenol methyl ether, eucalyptol, farnesol, fenchone, fenchyl acetate, Geranyl acetate, geranyl formate, heliotropin, heptincarboxylic acid methyl ester, Heptaldehyde, hydroquinone di-methyl ether, hydroxycinnamaldehyde, hydroxycinnamyl alcohol, Indole, iron, isoeugenol, isoeugenol methyl ether, isosafrole, jasmon, Camphor, Karvakrol, Karvon, p-cresol methyl ether, coumarin, p-methoxyacetophenone, Methyl n-amyl ketone, methyl anthranilate, p-methyl acetophenone, Methylchavikol, p-methylquinoline, methylnaphthylketone, methyl-n-nonylacetaldehyde, Methyl n-nonyl ketone, Muskon, naphthol ethyl ether, naphthol methyl ether, Nerol, nitrobenzene, n-nonylaldehyde, nonyl alcohol, n-octylaldehyde, p-oxy-acetophenone, Pentadecanolide, phenylethyl alcohol, phenylacetaldehyde dimethyacetal, Phenylacetic acid, pulegone, safrole, salicylic acid isoamyl ester, Salicylic acid methyl ester, salicylic acid hexyl ester, Salicylic acid cyclohexyl ester, santalol, skatole, terpineol, Thymen, thymol, undelactone, vanilin, veratrum aldehyde, cinnamaldehyde, Zimatalkohol, cinnamic acid, cinnamic acid ethyl ester, Zimtsäurebenzylester.

To the more volatile odoriferous substances, which are part of the present invention can be used advantageously include especially the lower-boiling fragrances natural or synthetic origin, used alone or in mixtures can be. Examples of more volatile Fragrances are alkyl isothiocyanates (alkyl mustard), butanedione, Limonene, linalool, linayl acetate / propionate, menthol, menthone, methyl-n-heptenone, Phellandrene, phenylacetaldehyde, terpinyl acetate, citral, citronellal.

All The aforementioned fragrances can be used alone or in a mixture.

Provided in a use according to the invention of the surface-modifying Composition for the preparation of a kit of this wound healing agent, coloring substances, indicator dyes, heat-dissipating substances Contains reagents and / or anti-inflammatory agents, these are known to the person skilled in the art and their preferred concentration can easily by expert without excessive Experimentation will be determined

A particular embodiment of the invention is the use a surface-modifying composition for the preparation a kit for topical and / or internal application to mammals, wherein the tissue is preferably surgically cut or traumatic Torn tissue is and it is in the affected tissue whole particularly preferably human skin, wherein the polymerisable Adhesive composition is preferably applied to a wound to close and / or cover.

The The invention also includes a kit for topical and / or internal use on tissue, in one or more separate containers a polymerizable monomeric adhesive composition and a Contains surface-modifying composition.

The polymerizable monomeric adhesive composition corresponds to already described above polymerizable monomeric adhesive composition, while the surface modifying composition at least one component selected from the group of contains oligomeric and / or polymeric Zerrorestadiermittel, wherein at least 30% of the monomers of the oligomeric and / or polymeric Zerrorestadiermittels about at least one functional group selected from ammonium, Amide, amine, anhydride, carbonyl, carboxylate, ethers, esters, hydroxyl, Formamide, imide, lactone, lactam, sulfone, oxazoline or urethane and the proportion of the respective oligomeric and / or polymeric Zerrorestadiermittels or mixtures thereof based on the total amount of the surface-modifying Composition 0.001-40 wt .-% makes up.

The kit also includes in a preferred embodiment of the invention, an oligomeric and / or polymeric Zerrorestadiermittel or mixtures thereof, wherein the weight fraction of the oligomeric and / or polymeric Zerrorestadiermittels or mixtures thereof based on the total amount of upper surface-modifying composition is preferably 0.01-20%, more preferably 0.10-10%, most preferably 0.15-5%, and most preferably 0.2-2.7%.

The Kit also contains in a special preferred Embodiment in one or more separate containers a polymerizable monomeric adhesive composition selected is prepared from n-butyl-2-cyanoacrylate, n-octyl-2-cyanoacrylate, 2-octyl-2-cyanoacrylate or from mixtures of said cyanoacrylates and a surface-modifying Composition.

The Contains surface-modifying composition while at least one oligomeric and / or polymeric Zerrorestadiermittel or mixtures thereof having a weight average molecular weight of 400 to 4000000 g / mol selected from homo- and / or Copoylmeren of polyvinylamines, polyvinylimines, polyvinylformamides, polyvinylpyrrolidones, Polyvinylcaprolactams, polymethylvinylethers, polyvinylacetates, Polyacrylamides, polysaccharides, polyoxazolines, polyurethanes, Polyester amides, polyethers, proteins or protein hydrolysates or from their mixtures.

In a most preferred embodiment the kit in one or more separate containers n-butyl-2-cyanoacrylate as polymerizable monomeric adhesive composition and homo- and / or copolymers of polyvinylamines, polyvinylimines or polyvinylformamides with a weight average molecular weight 400 to 400,000 g / mol or their Mixtures as a surface-modifying composition.

In a further particularly preferred embodiment of the Invention is at least part of the surface modifying Composition on a carrier material for administration absorbed, wherein the carrier material is preferably made of the Group of fibrous and / or porous materials is selected.

embodiments

Zerlaufflächenbestimmung

In order to mimic the hydrophilic character of a tissue surface, an aqueous solution of the polyvinyl alcohol Mowiol 3-88 ex Clariant is distributed homogeneously over the entire surface of a polyamide specimen. After drying, 0.5 ml of a surface-modifying composition is homogeneously distributed on half of the surface of the pretreated polyamide test specimen. The other half serves as a reference surface. After drying, 10 .mu.l of n-butyl cyanoacrylate with an Eppendorf pipette in the form of an approximately 15 mm long strip each on both halves of the specimen are added. The maturing area is evaluated according to the following schemes: Scheme for evaluation of the maturing area: Greater: Significantly larger running surface compared to the reference. A little bigger: Larger surface area compared to the reference. Equal: Equal size of running surface compared to the reference. A little smaller: Smaller running surface compared to the reference. Smaller: Significantly smaller running surface compared to the reference.

Determination of the curing time

First, 2.5 cm × 10 cm ABS specimens ex Wiliaam Cox Ireland Ltd. cleaned with a cellulose cloth soaked in isopropanol. Then, with the aid of a glass pipette, 0.5 ml of a surface-modifying composition is applied to the 322.6 mm ² (25 mm × 12.9 mm) adhesive area marked in pencil by means of a glass pipette. ABS specimens that are not treated with a surface-modifying composition are for reference. After drying, the curing time of the cyanoacrylate adhesives can be determined by adding 5 .mu.l of n-butyl cyanoacrylate with an Eppendorf pipette to the bonding surface of 322.6 mm ² . Subsequently, two test pieces are joined against each other and fixed with metal clamps.

• [1] Lupasol^® FG ex BASF AG.
• [2] Lupamin^® 5095 ex BASF AG wird zunächst bei RT in H₂O gelöst, dann mit Ethanol versetzt.
• Lupamin^® 5095 ist ein Polyvinylamin mit einer gewichtsmittleren Molmasse von ca. 45000 g/mol.
• Lupaspl^® FG ist ein Polyethylenimin mit einer gewichtsmittleren Molmasse von ca. 800 g/mol.

Versuchsergebnisse Oberflächenmodifizierende Zerlauffläche^[1] Aushärtzeit^[2] Zusammensetzungen [s] Referenzoberfläche Referenz 22 A Kleiner n. b. B Kleiner 12 C Kleiner 10

• [1] Bestimmt auf einem mit einer wässrigen Lösung von Mowioll 3-88 ex Clariant vorbehandelten Polyamidprüfkörper.
• [2] Bestimmt auf einem ABS-Prüfköper ex Wiliaam Cox Ireland Ltd.

The determination of the time at which curing of the adhesive bond is achieved, after releasing the metal brackets by the application of a tensile force, which is exercised by a weight of 1 kg. If the adhesive bond is able to withstand this tensile force for at least 5 seconds, then this time point defined as the time of curing. Used Surface Modifying Compositions surface modification Polymer in% by weight solvent compositions A ^[1] 0.25% Lupasol ^® FG EtOH B ^{[ 2]} 0.25% Lupamin 5095 ^® 60% H ₂ O / 40% EtOH C ^[2] 2.50% Lupamin ^® 5095 60% H ₂ O / 40% EtOH

• [1] Lupasol ^® FG from BASF AG.
• [2] Lupamin 5095 ^® ex BASF AG is first dissolved at RT in H ₂ O, then added with ethanol.
• Lupamin ^® 5095 is a polyvinylamine with a weight average molecular weight of about 45000 g / mol.
• Lupaspl ^® FG is a polyethyleneimine with a weight average molecular weight of approx. 800 g / mol.

test results surface modification Running surface ^[1] Curing time ^[2] compositions [S] reference surface reference 22 A Smaller nb B Smaller 12 C Smaller 10

• [1] Determined on a polyamide specimen pretreated with an aqueous solution of Mowioll 3-88 ex Clariant.
• [2] Intended on an ABS specimen ex Wiliaam Cox Ireland Ltd.

The Experimental results show that for all three surface-modifying Compositions the running surface of n-butyl cyanoacrylate could be reduced significantly. At the same time succeeded a significant Acceleration of the polymerization process.

QUOTES INCLUDE IN THE DESCRIPTION

This list The documents listed by the applicant have been automated generated and is solely for better information recorded by the reader. The list is not part of the German Patent or utility model application. The DPMA takes over no liability for any errors or omissions.

Cited patent literature

• US 5,328,887 [0003]
• - US 3527841 [0003, 0007]
• US 3722599 [0003]
• - US 3995641 [0003]
• US 3940362 [0003]
• - US 3667472 [0005]
• - US 3559652 [0005, 0012]
• US 5665817 [0007]
• - EP 1206291 b1 [0008]
• EP 1073484 B1 [0012]
• - US 4042442 [0013]

Cited non-patent literature

• - S. Arctander, Perfume and Flavor Materials, Vol. I and II, Montclair, NJ, 1969, self-published [0072]
• K. Bauer, D. Garbe and H. Surburg, Common Fragrance and Flavor Materials, 3rd. Ed., Wiley-VCH, Weinheim 1997 [0072]

Claims (24)

Using a surface-modifying Composition for the preparation of a kit for topical and / or internal application to tissue, with the surface-modifying Composition at least one component selected from the group of monomolecular, oligomeric and / or polymeric Zerrorestadiermittel which is suitable for the polymerization of a polymerizable monomeric adhesive composition on the tissue surface initiate and / or accelerate and flow limitation a monomeric polymerizable adhesive composition in the Application to achieve the tissue surface, wherein the proportion of each Zerrorestadiermittels or their mixtures based on the total amount of the surface-modifying composition 0.001-40 wt.% And each monomolecular, deliquescent, re-solidifying agent and / or at least 30% of the monomers of an oligomeric and / or polymeric Zerrorestadiermittels over at least one functional Group selected from ammonium, amide, amine, anhydride, carbonyl, Carboxylate, ether, ester, hydroxyl, formamide, imide, lactone, lactam, Sulfone, oxazoline or urethane. Use according to claim 1, characterized that the kit is in one or more separate containers (A) a polymerizable monomeric adhesive composition (B) contains a surface-modifying composition. Use according to one of the preceding claims, characterized in that the proportion of the monomeric, oligomeric and / or polymeric flow-restoring agent or mixtures thereof based on the total amount of surface-modifying Composition preferably 0.01-20 wt .-%, more preferably 0.10-10% by weight, most preferably 0.15-5 Wt .-% and most preferably 0.2-2.7 wt .-% makes. Use according to at least one of claims 1 to 3, characterized in that the polymerizable adhesive composition contains as a component a cyanoacrylate monomer according to formula (I) or a mixture of a cyanoacrylate monomer according to formula (I) with further cyanoacrylates, where R is a substituted or unsubstituted, straight-chain is branched or cyclic allyl, alkoxyalkyl, alkyl, alkenyl, haloalkyl or alkynyl group comprising 1 to 18 carbon atoms and / or includes an aromatic group or acyl group.

Formula (I) Use according to claim 5, characterized R is selected from the following groups: allyl, beta-methoxy-ethyl, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, n-pentyl, iso-pentyl cyclopentyl, n-hexyl, iso-hexyl, cyclohexyl, n-heptyl, isoheptyl, cycloheptyl, methoxyisopropyl, ethoxyethyl, iso-propoxyethyl, 2-butoxyethyl, n-octyl, 1-octyl, 2-octyl, 3-octyl, 4-octyl, decyl, dodecyl or lactoyl. Use according to at least one of the claims 1 to 5, characterized in that the monomolecular Zerrorestadiermittel is preferably selected from the group of carboxylates, Hydroxides, sulfonates, stearates, pyrazines, amines, amides, acetates, Ammonium compounds, or non-ionic surfactants or mixtures the said monomolecular cerium derivative. Use according to claim 6, characterized that selected the monomolecular Zerrorestadiermittel is from 3,5-dibromopyridine, dialkylethanolamines and tribenzylamine or mixtures of the substances mentioned. Use according to at least one of the claims 1 to 5, characterized in that the oligomeric and / or polymeric Degree of flow restricting agent having a weight-average molar mass of 400 to 4,000,000 g / mol is preferably selected from the Group of homo- and copolymers of polyvinylamines, polyvinylimines, Polyvinylformamides, polyvinylpyrrolidones, polyvinylcaprolactams, Polymethyl vinyl ethers, polyvinyl acetates, polyacrylamides, polysaccharides, Polyoxazolines, polyurethanes, polyester amides, polyethers, proteins or protein hydrolysates or mixtures thereof. Use according to at least one of the claims 1 to 8, characterized in that the surface-modifying Composition as further component an organic alcohol, Mixtures of different organic alcohols or mixtures of a or more organic alcohols with water, wherein the proportion by weight of the organic alcohol, the mixtures various organic alcohols or mixtures of one or several organic alcohols with water based on the total amount of at least 60% of the surface-modifying composition, preferably at least 80%, more preferably at least 90% and most preferably at least 95%. Use according to at least one of the claims 1 to 9, characterized in that the organic alcohol is selected is from ethanol, n-propanol, i-propanol, n-butanol, 2-butanol, i-butanol, 1,3-butanediol, phenoxyethanol, 1,2-propylene glycol and glycerine and from mixtures of the mentioned alcohols. Use according to at least one of the claims 1 to 10, characterized in that the monomolecular, oligomeric or polymeric deliquescent or a mixture of said Dissolvent in the organic alcohol, in the mixture of various organic alcohols or in the mixture of one or more organic Alcohols are dispersed with water and / or dissolved. Use according to at least one of the claims 1 to 11, characterized in that the surface-modifying Composition in the form of a liquid, as a gel, as Suspension or as a paste. Use according to at least one of the claims 1 to 12, characterized in that in at least one container additionally selected at least one further component from the groups of antimicrobial agents, the plasticizer, thickeners, stabilizers, skin-care active substances, the perfume, the healing agent, the coloring substances, the indicator dyes and / or the heat-dissipating reagents is included. Use according to at least one of the claims 1 to 13, characterized in that the tissue is human skin is. Use according to at least one of the claims 1 to 14, characterized in that the tissue is surgically cut or traumatically ripped tissue. Use of at least one of the claims 1 to 15, characterized in that the polymerizable adhesive composition is applied to close a wound and / or to cover. Use according to at least one of the claims 1 to 16, characterized in that the polymerizable adhesive composition sterilized by the following methods or combinations of the following methods was: heat, ultrafiltration, irradiation. Kit for topical and / or internal use Tissue containing in one or more separate containers: (A) a polymerizable monomeric adhesive composition (B) containing a surface modifying composition at least one component selected from the group of oligomeric and / or polymeric Zerrorestadiermittel, wherein at least 30% of the monomers of an oligomeric and / or polymeric Zerrorestadiermittels about at least one functional group selected from ammonium, Amide, amine, anhydride, carbonyl, carboxylate, ethers, esters, hydroxyl, Formamide, imide, lactone, lactam, sulphone, oxazoline or urethane, wherein the proportion of the respective oligomeric and / or polymeric Zerrorestadiermittels or mixtures thereof based on the total amount of the surface-modifying Composition 0.001-40 wt .-% makes up. Kit according to claim 18, characterized in that the proportion of the oligomeric and / or polymeric Zerrorestadiermittels or mixtures thereof based on the total amount of the surface-modifying Composition preferably 0.01-20 wt .-%, more preferably 0.10-10% by weight, most preferably 0.15-5 Wt .-% and most preferably 0.2-2.7 wt .-% makes. A kit according to any one of claims 18 or 19, comprising in one or more separate containers: (a) a polymerizable monomeric adhesive composition selected from n-butyl-2-cyanoacrylate, n-octyl-2-cyanoacrylate, 2-octyl-2-cyanoacrylate or mixtures of said cyanoacrylates (b) a surface-modifying composition comprising at least one oligomeric and / or polymeric deletion retarder or mixtures thereof having a weight-average molecular weight of from 400 to 4,000,000 g / mol selected from homo- and / or copolymers of polyvinylamines, polyvinylimines, polyvinylformamides, polyvinylpyrrolidones, polyvinylcaprolactams, polymethylvinylethers, Polyvinyl acetates, polyacrylamides, polysaccharides, polyoxazolines, polyurethanes, polyester amides, polyethers, proteins or protein hydrolysates or mixtures thereof. Kit according to at least one of the claims 18 to 20, containing in one or more separate containers: (A) n-butyl-2-cyanoacrylate as a polymerizable monomeric adhesive composition (B) Homo- and / or Copoylmere of polyvinylamines, polyvinylimines or Polyvinylformamides having a weight average molecular weight of 400 to 400,000 g / mol or mixtures thereof as surface-modifying Composition. Kit according to at least one of the claims 18 to 21, characterized in that at least a part of the surface-modifying Composition on a carrier material for administration is absorbed. Kit according to claim 22, characterized in that the carrier material is selected for administration is from the group of fibrous and / or porous Materials. Kit according to at least one of the claims 18 to 23, characterized in that the polymerizable adhesive composition sterilized by the following methods or combinations of the following methods was: heat, ultrafiltration, irradiation.