DE102023201127A1 - Medical device and process for manufacturing the medical device - Google Patents

Abstract

The invention relates to a medical device comprising a thread or a plurality of threads, wherein the medical device comprises a dihydrotriazine compound, a tautomer thereof or a salt thereof.
Furthermore, the invention relates to a method for producing the medical device.

Description

The invention relates to a medical device and a method for producing the medical device.

FIELD OF APPLICATION AND STATE OF THE ART

Medical products such as surgical suture materials and hernia meshes are well known. Various materials are used for this. For example, a hernia mesh comprising or consisting of monofilament polypropylene for the repair of abdominal wall and inguinal hernias is commercially sold by the applicant under the name Optilene® Mesh Elastic. Hernia meshes made of monofilament polyester and a collagen film are also well known and are available on the market under the name SymboTex ^® Composite Mesh.

Suture materials and hernia meshes can be treated with antimicrobial substances. Chlorhexidine gluconate, chlorhexidine acetate, polyhexamethylene biguanide (polihexanide), triclosan and octenidine are preferred antimicrobial substances.

Chlorhexidine gluconate is used for the manufacture of surgical suture material. An example of a commercially available suture material containing chlorhexidine is the product marketed commercially by the applicant under the name Novosyn ^® CHD.

Chlorhexidine gluconate or chlorhexidine acetate has been known for over 60 years and can be found in a wide range of products. However, the compound has only limited stability and forms toxic by-products and degradation products when stored for long periods or exposed to high temperatures (e.g. heat sterilization). In addition, its effectiveness against fungi, including yeasts, is only weak.

Polyhexamethylene biguanide (polihexanide) can be used for coating catheters as well as in wound dressings, gauzes and dressing materials. Polihexanide is an oligomer that consists of several individual substances. Analytical characterization is not easy. And the effectiveness of polihexanide against fungi, including yeasts, is similar to chlorhexidine, but only weak. A biocompatible suture material containing polihexanide is used in the EP 2 359 874 B1 described.

Triclosan is used for surgical sutures. A suture material with a corresponding coating is commercially available, for example under the name Vicryl plus. Triclosan is easily absorbed by the body. However, triclosan has since been classified as questionable by the FDA (Food and Drug Administration) and may no longer be used in certain products for external use. A major disadvantage that has been known for some time is the formation of cross-resistance of triclosan in combination with antibiotics in bacteria, e.g. Pseudomonas aeruginosa. ( doi: 10.1128/AAC.45.2.428-432.2001 Since antibiotics are often administered during surgical procedures, the simultaneous use of materials containing triclosan represents a risk factor.

Furthermore, the impregnation of suture material with octenidine (palmitate) is known ( https://bmcmicrobiol.biomedcentral.com/articles/10.1186/s12866-015-0523-4 ).

Furthermore, octenidine hydrochloride has established itself as a cationic active ingredient for antiseptic solutions and gels for use on skin, mucous membranes and wounds. Corresponding products are known, for example, under the names Octenisept ^® and Octenilin ^® . However, octenidine is also rather weakly effective against yeasts and fungi. In addition, a comparatively high cytotoxicity and moderate tolerability restrict the use of octenidine for products with long-term contact with living tissue.

From the EP 1 574 503 A1 Dihydrotriazine compounds are known. These can be used to manufacture various dosage forms, such as tablets, pills, capsules, powders, granules, suppositories, injections, pastes, ointments, creams, gels, gel-like creams, lotions, emulsions, suspensions, poultices, plasters, liniments, aerosols, syrups, oral preparations, eye drops and nasal drops for the treatment and prevention of bacterial infectious diseases as well as for disinfection and sterilization.

From the WO 2020/108880 A1 is a composition for the treatment of mucous membranes and wounds. In addition to femotaxidine, the composition contains a defoamer.

From the WO 2020/108881 A1 A composition for the treatment of mucous membranes and wounds is known, which contains a surfactant in addition to femotaxidine.

There is still a need for medical products, particularly those with antimicrobial effects.

TASK AND SOLUTION

The invention is based on the object of providing a medical product which in particular at least partially avoids the disadvantages mentioned in connection with the prior art.

This object is achieved according to the invention by a medical device having the features of independent claim 1. Preferred embodiments of the medical device are the subject of the dependent claims and the description. The wording of all claims is hereby made part of the content of the description by express reference.

According to a first aspect of the invention, the invention relates to a medical product, in particular a medical product that is effective or equipped with antimicrobial properties, in particular an antibacterial and/or antimycotic product or product. The medical product is preferably a textile-designed medical product. The medical product preferably has one thread, in particular only one thread, or a plurality of threads, i.e. several threads.

wobei

• - R₁ (i) eine Phenylgruppe oder eine Phenylalkylgruppe, von denen jede optional mit 1 bis 3 Substituenten, ausgewählt aus der Gruppe bestehend aus C_1-6-Alkoxygruppe, Hydroxygruppe, einem Halogenatom, C_1-6-Halogenalkylgruppe, C_1-6-Alkylgruppe, einer Sulfonamidogruppe und C_1-6-Halogenalkoxygruppe, substituiert ist, (ii) eine Naphthylgruppe oder eine Naphthylalkylgruppe, (iii) eine heterocyclische Gruppe, eine heterocyclische Alkylgruppe oder eine heterocyclische Aminoalkylgruppe, (iv) eine Alkylgruppe mit 1 bis 16 Kohlenstoffatomen oder (v) eine Cycloalkylgruppe oder eine Cycloalkyl-alkylgruppe bedeutet,
• - R₁' ein Wasserstoffatom, das an Position 1 oder 3 des Dihydrotriazinrings an das Stickstoffatom gebunden ist, bedeutet,
• - R₂ und R₃ unabhängig voneinander ein Wasserstoffatom oder eine Methylgruppe bedeuten,
• - R₄ eine Alkylgruppe mit 7 bis 16 Kohlenstoffatomen bedeutet und
• - die Strichlinie angibt, dass die Stellung einer Doppelbindung entweder zwischen den Positionen 1 und 2 oder zwischen den Positionen 2 und 3 des Dihydrotriazinrings liegt.

The medical device is characterized in particular by the fact that it comprises a dihydrotriazine compound of the following general formula I, a tautomer thereof or a salt thereof:

where

• - R ₁ represents (i) a phenyl group or a phenylalkyl group, each of which is optionally substituted by 1 to 3 substituents selected from the group consisting of C _1-6 alkoxy group, hydroxy group, a halogen atom, C _1-6 haloalkyl group, C _1-6 alkyl group, a sulfonamido group and C _1-6 haloalkoxy group, (ii) a naphthyl group or a naphthylalkyl group, (iii) a heterocyclic group, a heterocyclic alkyl group or a heterocyclic aminoalkyl group, (iv) an alkyl group having 1 to 16 carbon atoms or (v) a cycloalkyl group or a cycloalkyl-alkyl group,
• - R ₁ ' represents a hydrogen atom bonded to the nitrogen atom at position 1 or 3 of the dihydrotriazine ring,
• - R ₂ and R ₃ independently represent a hydrogen atom or a methyl group,
• - R ₄ represents an alkyl group having 7 to 16 carbon atoms and
• - the dashed line indicates that the position of a double bond is either between positions 1 and 2 or between positions 2 and 3 of the dihydrotriazine ring.

The term “dihydrotriazine compound” is understood in the context of the present invention to mean a compound with a six-membered triazine ring having only two double bonds, ie a so-called dihydrotriazine ring, where the triazine ring or dihydrotriazine ring has a ring nitrogen atom at positions 1, 3 and 5 and a ring nitrogen atom at positions 2, 4 and 6. ring carbon atom and wherein the position of one double bond is between positions 4 and 5 of the triazine or dihydrotriazine ring and the position of the other, ie second or remaining, double bond is either between positions 1 and 2 or between positions 2 and 3 of the triazine ring or dihydrotriazine ring.

The term “fungi” in the sense of the present invention can mean unicellular or multicellular fungi.

For the purposes of the present invention, the term “yeasts” refers to single-celled fungi which reproduce by budding or division (so-called yeast fungi).

For the purposes of the present invention, the term “phenyl group” is understood to mean a benzene radical, i.e. the atomic group -C ₆ H ₅ .

For the purposes of the present invention, the term “benzyl group” refers to the phenylmethyl group -CH ₂ -C ₆ H ₅ , formerly also referred to as α-tolyl group.

The term "phenylalkyl group" in the sense of the present invention means a group in which a linear, i.e. unbranched, or branched alkyl group or alkylene group, in particular with 1 to 6 carbon atoms, is bonded to a phenyl group. The alkyl group or alkylene group can be a substituted or unsubstituted alkyl group or alkylene group. The phenylalkyl group is preferably a benzyl group, methylbenzyl group such as in particular 4-methylbenzyl group, 1-phenylethyl group, 2-phenylethyl group, 1-phenylpropyl group, 2-phenylpropyl group or 3-phenylpropyl group.

A benzene ring of the phenyl group or phenylalkyl group may have one to three substituents, in particular selected from the group consisting of halogen atom, hydroxy group, C _1-6 alkyl group, C _1-6 haloalkyl group, C _1-6 alkoxy group, C _1-6 haloalkoxy group and sulfonamido group.

The term “halogen atom” in the context of the present invention can mean a fluorine atom, a chlorine atom, a bromine atom or an iodine atom.

The expression "C _1-6 alkyl group" can mean in the sense of the present invention a corresponding linear or branched alkyl group, ie a linear or branched alkyl group having 1 to 6 carbon atoms. The alkyl group can be a substituted or unsubstituted alkyl group. For example, the C _1-6 alkyl group can be a methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, sec-butyl group, tert-butyl group, n-pentyl group, sec-pentyl group, isopentyl group, neopentyl group, n-hexyl group or isohexyl group.

The term “C _1-6 haloalkyl group” in the sense of the present invention can mean in particular a chloromethyl group, bromomethyl group, 1-chloroethyl group or trifluoromethyl group.

The term “C _1-6 alkoxy group” in the sense of the present invention can mean in particular a methoxy group, ethoxy group, n-propoxy group, isopropoxy group, n-butoxy group or isobutoxy group.

The term “C _1-6 haloalkoxy group” in the sense of the present invention can mean in particular a trifluoromethoxy group.

The term “naphthyl group” in the sense of the present invention can mean a 1-naphthyl group or a 2-naphthyl group.

The term “naphthylalkyl group” in the sense of the present invention means a group in which a linear, i.e. unbranched, or branched alkyl group, in particular with 1 to 6 carbon atoms, is bonded to a naphthyl group. The alkyl group can be a substituted or unsubstituted alkyl group. The naphthylalkyl group is preferably a 1-naphthylmethyl group, 2-naphthylmethyl group, 1-naphthylethyl group or 2-naphthylethyl group.

The term “heterocyclic group” in the context of the present invention means a three- to six-membered heterocyclic group which contains one to three atoms selected from the group consisting of of nitrogen atom, oxygen atom and sulphur atom, where a benzene ring can be fused or condensed to the heterocyclic group. The heterocyclic group can, for example, be a pyridyl group, a pyrazinyl group, a thiazolyl group, a piperidyl group, a piperazyl group, a tetrahydrofuryl group, a thienyl group, a pyrrolyl group, a pyrrolidinyl group, an oxazolyl group, an imidazolyl group, an isooxazolyl group, an isothiazolyl group, a pyrazolyl group, a tetrahydropyranyl group, a 2-oxotetrahydropyranyl group, a pyrimidinyl group, a pyradizinyl group, a morpholinyl group, a 1,3,5-triazinyl group, a 1,2,4-triazinyl group, a quinolyl group or an isoquinolyl group.

In particular, the heterocyclic group in the sense of the present invention can be a 2-pyridyl group, a 3-pyridyl group, a 4-pyridyl group, a 2-furyl group, a 2-thiazolyl group, a 1-piperidyl group, a 1-piperazyl group, a 2-quinolyl group, a 3-quinolyl group, a 4-quinolyl group, a 5-quinolyl group, an 8-quinolyl group, a 1-isoquinolyl group, a 3-isoquinolyl group, a 4-isoquinolyl group or a 5-isoquinolyl group.

The term "heterocyclic alkyl group" in the sense of the present invention means a group in which a linear, i.e. unbranched, or branched alkyl group, in particular with 1 to 6 carbon atoms, is bonded to a heterocyclic group, in particular as defined or described in the previous paragraphs. The alkyl group can be a substituted or unsubstituted alkyl group. Preferably, the heterocyclic alkyl group is a 2-pyridylmethyl group, 3-pyridylmethyl group, 4-pyridylmethyl group, 2-pyridylethyl group, 3-pyridylethyl group, 4-pyridylethyl group, pyrazinylmethyl group, pyrazinylethyl group, 2-furylmethyl group, 2-furylethyl group, 2-thiazolylmethyl group, 2-thiazolylethyl group, 4-piperidylmethyl group, 2-quinolylmethyl group, 3-quinolylmethyl group, 4-quinolylmethyl group, 5-quinolylmethyl group, 8-quinolylmethyl group, 1-isoquinolylmethyl group, 3-isoquinolylmethyl group, 4-isoquinolylmethyl group or 5-isoquinolylmethyl group.

The term "heterocyclic aminoalkyl group" in the sense of the present invention means a group in which a linear, i.e. unbranched, or branched alkyl group, in particular with 1 to 12 carbon atoms, is bonded to a heterocyclic amino group. The alkyl group can be a substituted or unsubstituted alkyl group. The heterocyclic aminoalkyl group is preferably a 4-amino-dihydro-1,3,5-triazin-2-yl-amino group, a 4-alkylamino-dihydro-1,3,5-triazin-2-yl-amino group or 4-phenylalkylamino-dihydro-1,3,5-triazin-2-yl-amino group.

The expression “alkyl group having 1 to 16 carbon atoms” means in the sense of the present invention a linear, i.e. unbranched, or branched alkyl group having 1 to 16 carbon atoms. The alkyl group can be a substituted or unsubstituted alkyl group. The alkyl group having 1 to 16 carbon atoms is preferably a methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, sec-butyl group, tert-butyl group, n-hexyl group, n-heptyl group, n-octyl group, tert-octyl group, n-nonyl group, n-decyl group, n-undecyl group, n-dodecyl group, n-tridecyl group, n-tetradecyl group, n-pentadecyl group or n-hexadecyl group.

The term "cycloalkyl group" in the sense of the present invention means in particular a cycloalkyl group having 3 to 6 carbon atoms. For example, the cycloalkyl group can be a cyclopropyl group, cyclobutyl group, cyclopentyl group or cyclohexyl group.

The term "cycloalkyl-alkyl group" in the sense of the present invention means in particular a group in which a linear, i.e. unbranched, or branched alkyl group, in particular with 1 to 6 carbon atoms, is bonded to a cycloalkyl group, in particular as defined or described in the previous paragraph. The alkyl group can be a substituted or unsubstituted alkyl group. The cycloalkyl-alkyl group is preferably a cyclohexylmethyl group, a 1-cyclohexylethyl group or a 2-cyclohexylethyl group.

The expression “alkyl group having 7 to 16 carbon atoms” means in the sense of the present invention a linear, i.e. unbranched, or branched alkyl group having 7 to 16 carbon atoms. The alkyl group can be a substituted or unsubstituted alkyl group. The alkyl group having 7 to 16 carbon atoms is preferably an n-heptyl group, n-octyl group, tert-octyl group, n-nonyl group, n-decyl group, n-undecyl group, n-dodecyl group, n-tridecyl group, n-tetradecyl group, n-pentadecyl group or n-hexadecyl group.

The term "salt" used in connection with the dihydrotriazine compound of the general formula I can, in the sense of the present invention, mean in particular a salt of the dihydrotriazine compound with an organic acid. The organic acid can, for example, be selected from the group consisting of formic acid, acetic acid, propionic acid, lactic acid, butyric acid, isobutyric acid, malic acid, maleic acid, malonic acid, fumaric acid, succinic acid, succinic acid monoamide, glutaric acid, tartaric acid, oxalic acid, citric acid, glycolic acid, glucuronic acid, ascorbic acid, aspartic acid, glutamic acid, benzoic acid, phthalic acid, salicylic acid, anthranilic acid, benzenesulfonic acid, p-toluenesulfonic acid or methanesulfonic acid. In particular, the organic acid can be a fatty acid, in particular with a linear or branched and/or saturated or unsaturated aliphatic radical. The aliphatic radical can have 8 carbon atoms to 22 carbon atoms. The aliphatic radical is preferably an alkyl or alkenyl radical. For example, the fatty acid can be selected from the group consisting of octanoic acid, decanoic acid, dodecanoic acid, tetradecanoic acid, hexadecanoic acid, octadecanoic acid, 12-hydroxystearic acid, isostearic acid, eicosanoic acid and behenic acid

• - R₁ eine Phenylgruppe oder eine Phenylalkylgruppe von denen jede optional durch 1 bis 3 Substituenten, ausgewählt aus der Gruppe bestehend aus Fluoratom, Chloratom, Hydroxygruppe, Methylgruppe, tert-Butylgruppe, Trifluoromethylgruppe und Methoxygruppe, substituiert ist,
• - R₁' ein Wasserstoffatom, das an Position 1 oder 3 des Dihydrotriazinrings an das Stickstoffatom gebunden ist,
• - R₂ und R₃ jeweils eine Methylgruppe und
• - R₄ eine n-Octylgruppe, n-Nonylgruppe oder n-Decylgruppe.

In the embodiment of the invention,

• - R ₁ is a phenyl group or a phenylalkyl group each of which is optionally substituted by 1 to 3 substituents selected from the group consisting of fluorine atom, chlorine atom, hydroxy group, methyl group, tert-butyl group, trifluoromethyl group and methoxy group,
• - R ₁ ' is a hydrogen atom bonded to the nitrogen atom at position 1 or 3 of the dihydrotriazine ring,
• - R ₂ and R ₃ each represent a methyl group and
• - R ₄ is an n-octyl group, n-nonyl group or n-decyl group.

• - R₁ eine Phenylgruppe, eine Benzylgruppe oder eine 2-Phenylethylgruppe, von denen jede optional durch 1 bis 3 Substituenten, ausgewählt aus der Gruppe bestehend aus Fluoratom, Chloratom, Hydroxygruppe, Methylgruppe, tert-Butylgruppe, Trifluoromethylgruppe und Methoxygruppe, substituiert ist,
• - R₁' ein Wasserstoffatom, das an Position 1 oder 3 des Dihydrotriazinrings an das Stickstoffatom gebunden ist,
• - R₂ und R₃ jeweils eine Methylgruppe und
• - R₄ eine n-Octylgruppe, n-Nonylgruppe oder n-Decylgruppe.

Preferred means/means

• - R ₁ represents a phenyl group, a benzyl group or a 2-phenylethyl group, each of which is optionally substituted by 1 to 3 substituents selected from the group consisting of fluorine atom, chlorine atom, hydroxy group, methyl group, tert-butyl group, trifluoromethyl group and methoxy group,
• - R ₁ ' is a hydrogen atom bonded to the nitrogen atom at position 1 or 3 of the dihydrotriazine ring,
• - R ₂ and R ₃ each represent a methyl group and
• - R ₄ is an n-octyl group, n-nonyl group or n-decyl group.

• - R₁ eine Benzylgruppe, welche optional durch 1 bis 3 Substituenten, ausgewählt aus der Gruppe bestehend aus Fluoratom, Chloratom, Hydroxygruppe, Methylgruppe, tert-Butylgruppe, Trifluoromethylgruppe und Methoxygruppe, bevorzugt durch 1 bis 3 Methylgruppen, besonders bevorzugt durch eine Methylgruppe, substituiert ist,
• - R₁' ein Wasserstoffatom, das an Position 1 oder 3 des Dihydrotriazinrings an das Stickstoffatom gebunden ist,
• - R₂ und R₃ jeweils eine Methylgruppe und
• - R₄ eine n-Octylgruppe, n-Nonylgruppe oder n-Decylgruppe.

Particularly preferred means/means

• - R ₁ is a benzyl group which is optionally substituted by 1 to 3 substituents selected from the group consisting of fluorine atom, chlorine atom, hydroxy group, methyl group, tert-butyl group, trifluoromethyl group and methoxy group, preferably by 1 to 3 methyl groups, particularly preferably by a methyl group,
• - R ₁ ' is a hydrogen atom bonded to the nitrogen atom at position 1 or 3 of the dihydrotriazine ring,
• - R ₂ and R ₃ each represent a methyl group and
• - R ₄ is an n-octyl group, n-nonyl group or n-decyl group.

• - R₁ eine Phenylgruppe, 4-Chlorophenylgruppe, 2,4-Difluorophenylgruppe, 2,3,4-Trifluorophenylgruppe, 4-tert-Butylphenylgruppe, 4-Methoxyphenylgruppe, 2-Methoxy-4-tert-butylphenylgruppe, 4-Trifluoromethoxyphenylgruppe, Benzylgruppe, Methylbenzlygruppe wie insbesondere 4-Methylbenzylgruppe, 4-Methoxybenzylgruppe, 3,4-Dimethoxybenzylgruppe, 4-Hydroxybenzylgruppe, 3,4-Dichlorobenzylgruppe, 2,3,4-Trichlorobenzylgruppe, 4-Trifluoromethylbenzylgruppe, 1-Phenylethylgruppe, 2-Phenylethylgruppe, 1-Phenylpropylgruppe, 2-Phenylpropylgruppe oder 3-Phenylpropylgruppe, bevorzugt eine Methylbenzylgruppe, besonders bevorzugt eine 4-Methylbenzylgruppe,
• - R₁' ein Wasserstoffatom, das an Position 1 oder 3 des Dihydrotriazinrings an das Stickstoffatom gebunden ist,
• - R₂ und R₃ jeweils eine Methylgruppe und
• - R₄ eine n-Octylgruppe, n-Nonylgruppe oder n-Decylgruppe.

In a further embodiment of the invention,

• - R ₁ is a phenyl group, 4-chlorophenyl group, 2,4-difluorophenyl group, 2,3,4-trifluorophenyl group, 4-tert-butylphenyl group, 4-methoxyphenyl group, 2-methoxy-4-tert-butylphenyl group, 4-trifluoromethoxyphenyl group, benzyl group, methylbenzyl group such as in particular 4-methylbenzyl group, 4-methoxybenzyl group, 3,4-dimethoxybenzyl group, 4-hydroxybenzyl group, 3,4-dichlorobenzyl group, 2,3,4-trichlorobenzyl group, 4-trifluoromethylbenzyl group, 1-phenylethyl group, 2-phenylethyl group, 1-phenylpropyl group, 2-phenylpropyl group or 3-phenylpropyl group, preferably a methylbenzyl group, particularly preferably a 4-methylbenzyl group,
• - R ₁ ' is a hydrogen atom bonded to the nitrogen atom at position 1 or 3 of the dihydrotriazine ring,
• - R ₂ and R ₃ each represent a methyl group and
• - R ₄ is an n-octyl group, n-nonyl group or n-decyl group.

In a further embodiment of the invention, R ₁ is/are a methylbenzyl group, preferably 4-methylbenzyl group, and/or R ₂ and R ₃ are each a methyl group and/or R ₄ is an n-octyl group. Preferably, R ₁ is/are a methylbenzyl group, preferably 4-methylbenzyl group, R ₂ and R ₃ are each a methyl group and R ₄ is an n-octyl group.

In a further embodiment of the invention, R ₁ is/are a methylbenzyl group, preferably 4-methylbenzyl group, R ₁ ' is a hydrogen atom which is bonded to the nitrogen atom at position 1 or 3 of the dihydrotriazine ring, R ₂ and R ₃ are each a methyl group and R ₄ is an n-octyl group.

Alternativ kann die Dihydrotriazinverbindung die nachfolgende Formel Ib aufweisen:

Particularly preferably, the dihydrotriazine compound has the following formula la:

Alternatively, the dihydrotriazine compound may have the following formula Ib:

In a further embodiment of the invention, the dihydrotriazine compound, the tautomer thereof or the salt thereof is 4-octylamino-1,6-dihydro-6,6-dimethyl-2-(4'-methylbenzylamino)-1,3,5-triazine gluconate, which can also be referred to as 6,6-dimethyl-N2-(4-methylbenzyl)-N4-octyl-1,6-dihydro-[1,3,5]triazine-2,4-diamine gluconate. Preferably, the dihydrotriazine compound, tautomer thereof, or salt thereof is 4-octylamino-1,6-dihydro-6,6-dimethyl-2-(4'-methylbenzylamino)-1,3,5-triazine-D-gluconate, which may also be referred to as 6,6-dimethyl-N2-(4-methylbenzyl)-N4-octyl-1,6-dihydro-[1,3,5]triazine-2,4-diamine-D-gluconate. The dihydrotriazine compound or dihydrotriazine compound salt disclosed in this paragraph has been found to be particularly effective in achieving the benefits of the invention.

The dihydrotriazine compound or the dihydrotriazine compound salt 4-octylamino-1,6-dihydro-6,6-dimethyl-2-(4'-methylbenzylamino)-1,3,5-triazine-D-gluconate mentioned in the previous paragraph is commercially available under the name "femotaxidine" and can be represented by the following formula Ia ^# :

In a further embodiment of the invention, the dihydrotriazine compound, the tautomer thereof or the salt thereof is 4-octylamino-3,6-dihydro-6,6-dimethyl-2-(4'-methylbenzylamino)-1,3,5-triazine gluconate, in particular 4-octylamino-3,6-dihydro-6,6-dimethyl-2-(4'-methylbenzylamino)-1,3,5-triazine-D-gluconate.

Preferably, the concentration of the dihydrotriazine compound, the tautomer thereof or the salt thereof is selected such that the medical device is antimicrobially effective against bacteria, in particular against gram-positive bacteria and/or against gram-negative bacteria, preferably against both gram-positive bacteria and gram-negative bacteria.

Preferably, the dihydrotriazine compound, tautomer thereof or salt thereof has a concentration of 0.001 mg to 20 mg, in particular 0.01 mg to 5 mg, preferably 0.01 mg to 2 mg, per gram of the medical device, thread or threads.

In a further embodiment of the invention, the dihydrotriazine compound, the tautomer thereof or the salt thereof is dispersed in the medical device, in the thread or in the threads, in particular homogeneously or non-homogeneously.

In a further embodiment of the invention, the dihydrotriazine compound, the tautomer thereof or the salt thereof forms a coating or a component of a composition, in particular coating, of the medical device, the thread or the threads. The coating or composition can be in the form of a gel, in particular hydrogel, for example. Furthermore, the coating or composition can have a layer thickness of 0.01 µm to 1000 µm, in particular 0.01 µm to 100 µm, preferably 0.05 µm to 20 µm. Furthermore, the coating or composition can have a uniform or uneven layer thickness. Furthermore, the coating or composition can be formed continuously or not continuously on the medical device, the thread or the threads. In other words, the medical device, the thread or the threads can be only partially or completely covered by the coating or composition. Furthermore, the coating can be formed in one layer or in multiple layers. Furthermore, the coating or composition can have a proportion of 0.001 wt.% to 1 wt.%, in particular 0.01 wt.% to 0.5 wt.%, preferably 0.01 wt.% to 0.2 wt.%, based on the total weight of the medical device, the thread or threads.

In a further embodiment of the invention, the medical device, the thread or threads, preferably the coating or composition of the medical device, the thread or threads, further comprises at least one further component, in particular selected from the group consisting of surface-active compound, complexing agent, film former and combinations, in particular mixtures, of at least two of the aforementioned components.

The term “surface-active compound” in the context of the present invention is to be understood as a compound which, due to its presence in a liquid, in particular in water or an aqueous liquid, increases the surface tension and/or interfacial tension of the liquid, in particular especially between two phases. The surface-active compound in the sense of the present invention can in particular be a surfactant.

The surface-active compound can be selected from the group consisting of nonionic surface-active compound, cationic surface-active compound, zwitterionic surface-active compound and combinations, in particular mixtures, of at least two of the aforementioned surface-active compounds.

For the purposes of the present invention, the term “nonionic surface-active compound” refers to a surface-active compound which does not contain any dissociable functional groups and therefore does not separate into ions in water or an aqueous liquid.

For the purposes of the present invention, the term “zwitterionic surface-active compound” refers to a compound which has both a negatively and a positively charged functional group (so-called amphoteric surface-active compound).

For the purposes of the present invention, the term “cationic surface-active compound” is to be understood as meaning a surface-active compound which has a positively charged functional group but not additionally a negatively charged group.

A non-ionic or zwitterionic surface-active compound has the particular advantage that no or few interactions occur with the dihydrotriazine compound and, moreover, it is very well tolerated by skin, mucous membranes and wounds.

The non-ionic surface-active compound is preferably selected from the group consisting of poloxamer, fatty alcohol alkoxylate such as fatty alcohol ethoxylate, polyvinylpyrrolidone, alkyl polyglucoside and combinations, in particular mixtures, of at least two of the aforementioned non-ionic surface-active compounds. The non-ionic surface-active compounds mentioned in this paragraph and described in more detail below have proven to be particularly suitable for reducing or avoiding an irritation potential of the dihydrotriazine compound, the tautomer thereof or the salt thereof that is disadvantageous from a wound therapy perspective.

For the purposes of the present invention, the term “poloxamer” refers to a block copolymer of ethylene oxide and propylene oxide (so-called EO/PO block copolymers).

The poloxamer preferably has 2 to 130 structural units -CH ₂ -CH ₂ -O- and/or 15 to 67 structural units -CHCH ₃ -CH ₂ -O- per molecule.

The poloxamer can in particular be poloxamer 407, poloxamer 188 or a combination, in particular a mixture, thereof.

The use of a poloxamer as a surface-active compound can be particularly preferred according to the invention, since poloxamers have not only surface-active properties but also foam-suppressing or foam-reducing properties and/or emulsifying properties. This makes it particularly advantageous to dampen, reduce or suppress foam formation caused by the dihydrotriazine compound, the tautomer thereof or the salt thereof. This in turn makes it possible to achieve a uniform coating or impregnation of the medical device, the thread or threads.

The use of polyvinylpyrrolidone as a surface-active compound can also be particularly preferred according to the invention, since this compound has emulsifying properties in addition to surface-active properties. This in turn can provide an optimal medium for coating or impregnating the medical device, the thread or threads. The advantages mentioned in the previous paragraph apply accordingly. In addition, the use of polyvinylpyrrolidone has the advantage that it can bind water and have a film-forming effect.

For the purposes of the present invention, the term “fatty alcohol alkoxylate” is to be understood as meaning a non-ionic surface-active compound whose lipophilic part comprises a fatty alcohol or consists of a fatty alcohol or is derived from a fatty alcohol and whose hydrophilic part comprises a polyalkylene glycol, in particular short- or medium-chain polyalkylene glycol, or consists of a polyalkylene glycol, in particular short or medium chain polyalkylene glycol, or is derived from a polyalkylene glycol, in particular short or medium chain polyalkylene glycol. The fatty alcohol and the polyalkylene glycol can independently have 8 carbon atoms to 22 carbon atoms. The fatty alcohol can in particular be an alcohol derived from caprylic, capric, lauric, palmitic, stearic or oleic acid or branched isononyl, issoundecyl, isotridecyl, isopentadecyl or isononadecyl alcohols. The fatty alcohol alkoxylate can also be referred to as a polyalkylene glycol ether in the sense of the present invention.

As already mentioned, the fatty alcohol alkoxylate can in particular be a fatty alcohol ethoxylate.

The fatty alcohol ethoxylate is preferably a polyoxyethylene ether of lauryl alcohol, a polyoxyethylene ether of myristyl alcohol, a polyoxyethylene ether of cetyl alcohol, a polyoxyethylene ether of cetylstearyl alcohol, a polyoxyethylene ether of stearyl alcohol, a polyoxyethylene ether of oleyl alcohol, a polyoxyethylene ether of isononane alcohol, a polyoxyethylene ether of issoundecane alcohol, a polyoxyethylene ether of isotridecane alcohol, a polyoxyethylene ether of isopentadecane alcohol, a polyoxyethylene ether of isoheptadecane alcohol, a polyoxyethylene ether of isononadecane alcohol or a combination, in particular a mixture, of at least two of the aforementioned polyoxyethylene ethers.

The fatty alcohol ethoxylate can in particular be selected from the group consisting of polyoxyethylene (4) lauryl ether, polyoxyethylene (7) lauryl ether, polyoxyethylene (9) lauryl ether, polyoxyethylene (23) lauryl ether, polyoxyethylene (2) cetyl ether, polyoxyethylene (10) cetyl ether, polyoxyethylene (20) cetyl ether, polyoxyethylene (6) cetylstearyl ether, polyoxyethylene (20) cetylstearyl ether, polyoxyethylene (25) cetylstearyl ether, polyoxyethylene (2) stearyl ether, polyoxyethylene (10) stearyl ether, polyoxyethylene (20) stearyl ether, polyoxyethylene (2) oleyl ether, polyoxyethylene (10) oleyl ether, polyoxyethylene (20) oleyl ether, polyoxyethylene (10) monodecyl ether, Polyoxyethylene (10) tridecyl ether" and combinations, in particular mixtures, of at least two of the aforementioned fatty alcohol ethoxylates.

In other words, the fatty alcohol ethoxylate can in particular be selected from the group consisting of Laureth-4, Laureth-7, Laureth-9, Laureth-23, Ceteth-2, Ceteth-10, Ceteth-20, Ceteareth-6, Ceteareth-20, Ceteareth-25, Steareth-2, Steareth-10, Steareth-20, Oleth-2, Oleth-10, Oleth-20, Deceth-10, Trideceth-10 and combinations, in particular mixtures, of at least two of the aforementioned fatty alcohol ethoxylates.

Fatty alcohol alkoxylates, especially fatty alcohol ethoxylates, have the advantage that they not only have surface-active properties, but also have an emulsifying effect and support the wetting of hydrophobic surfaces.

For the purposes of the present invention, the term "alkyl polyglucoside" is understood to mean a nonionic sugar surfactant which has one or more glucose building blocks and an alkyl radical, in particular a long-chain alkyl radical, or which consists of one or more glucose building blocks and an alkyl radical, in particular a long-chain alkyl radical. The glucose building block or blocks function as a hydrophilic component, while the alkyl radical represents the hydrophobic group.

The alkyl polyglucoside preferably has 1 to 5 glucose units and/or an alkyl radical having 6 carbon atoms to 22 carbon atoms, preferably 6 carbon atoms to 20 carbon atoms, in particular 6 carbon atoms to 16 carbon atoms, in particular 8 carbon atoms to 14 carbon atoms.

The alkyl polyglucoside is preferably a C ₈ to C ₂₀ alkyl polyglucose, in particular C ₈ to C ₁₆ alkyl polyglucose.

The alkyl polyglucoside is particularly preferably lauryl polyglucose, decyl polyglucose, cocoyl polyglucose or a combination, in particular a mixture, of at least two of the aforementioned alkyl polyglucosides. The alkyl radical of the decyl polyglucose preferably has 8 carbon atoms to 16 carbon atoms, in particular 10 carbon atoms. The alkyl radical of the lauryl polyglucose preferably has 12 carbon atoms to 16 carbon atoms, in particular 12 carbon atoms. The alkyl radical of the cocoyl polyglucose preferably has 8 carbon atoms to 16 carbon atoms.

Alkylpolyglucosides also have the advantage that they not only have surface-active properties, but also represent emulsifying compounds.

The zwitterionic surface-active compound is preferably an alkyl betaine and/or alkylamidoalkyl betaine, in particular an alkylamidoethyl betaine, alkylamidopropyl betaine or a combination, in particular a mixture, thereof.

The alkyl betaine may preferably have alkyl groups which independently of one another have 8 carbon atoms to 22 carbon atoms, in particular 8 to 18 carbon atoms.

The alkylamidoalkylbetaine particularly preferably has at least one fatty acid residue, in particular only one fatty acid residue, (only) two fatty acid residues or three fatty acid residues. The at least one fatty acid residue preferably has 8 carbon atoms to 22 carbon atoms, in particular 8 to 18 carbon atoms. The fatty acid residue can in particular be a saturated or unsaturated fatty acid residue. The fatty acid residue is preferably a caprylic acid residue, capric acid residue, undecylenic acid residue (undec-10-enoic acid residue), undecylic acid residue (n-undecanoic acid residue), lauric acid residue, stearic acid residue, ricinoleic acid residue or coconut fatty acid residue.

Preferably, the alkylamidoalkylbetaine is selected from the group consisting of caprylamidoalkylbetaine, caprimidoalkylbetaine, undecylenamidoalkylbetaine, undecylamidoalkylbetaine, lauramidoalkylbetaine, lauryldimethylaminoacetic acidbetaine, stearinamidoalkylbetaine, ricinolamidoalkylbetaine, cocamidoalkylbetaine and combinations, in particular mixtures, of at least two of the aforementioned alkylamidoalkylbetaines.

The alkylamidoethyl betaine is preferably an alkylamidoethyl betaine based on a fatty acid, in particular a fatty acid with 8 carbon atoms to 22 carbon atoms, in particular 8 carbon atoms to 18 carbon atoms. The fatty acid can in particular be a saturated or unsaturated fatty acid. The fatty acid is preferably caprylic acid, capric acid, undecylenic acid (undec-10-enoic acid), undecylic acid (n-undecanoic acid), lauric acid, stearic acid, ricinoleic acid or coconut fatty acid.

The alkylamidoethylbetaine is particularly preferably selected from the group consisting of caprylamidoethylbetaine, caprimidoethylbetaine, undecylenamidoethylbetaine, undecylamidoethylbetaine, lauramidoethylbetaine, cocamidoethylbetaine, stearinamidoethylbetaine, ricinolamidoethylbetaine and combinations, in particular mixtures, of at least two of the aforementioned alkylamidoethylbetaines.

The alkylamidopropyl betaine is preferably an alkylamidopropyl betaine based on a fatty acid, in particular a fatty acid with 8 carbon atoms to 22 carbon atoms, in particular 8 carbon atoms to 18 carbon atoms. The fatty acid can in particular be a saturated or unsaturated fatty acid. The fatty acid is preferably caprylic acid, capric acid, undecylenic acid (undec-10-enoic acid), undecylic acid (n-undecanoic acid), lauric acid, stearic acid, ricinoleic acid or coconut fatty acid.

The alkylamidopropyl betaine is particularly preferably selected from the group consisting of caprylamidopropyl betaine, caprimidopropyl betaine, undecylenamidopropyl betaine, undecylamidopropyl betaine, cocamidopropyl betaine, stearinamidopropyl betaine, ricinolamidopropyl betaine and combinations, in particular mixtures, of at least two of the aforementioned alkylamidopropyl betaines.

The cationic surface-active compound preferably has a saturated or unsaturated organic radical, in particular an alkyl group, having 8 carbon atoms to 22 carbon atoms.

The cationic surface-active compound can in particular be selected from the group consisting of distearyldimethylammonium chloride, didecyldimethylammonium chloride, cetyltrimethylammonium chloride, cetyltrimethylammonium bromide, cetylpyridinium chloride, mecetronium ethyl sulfate and combinations, in particular mixtures, thereof.

The surface-active compound preferably has a proportion of 0.001 wt.% to 50 wt.%, in particular 0.01 wt.% to 40 wt.%, preferably 0.1 wt.% to 30 wt.%, based on the Total weight of the medical device, thread or threads, preferably the coating or composition of the medical device, thread or threads.

The complexing agent is preferably selected from the group consisting of citric acid, tartaric acid, succinic acid, methylglycine diacetate, ethyldiaminetetraacetate, N,N'-bis-(carboxymethyl)-L-glutamate, polyaspartic acid, iminodisuccinate, phosphonates, phosphonobutanetricarboxylic acid, lauryl alcohol diphosphonic acid, editronic acid, salts of the aforementioned complexing agents and combinations, in particular mixtures, of at least two of the aforementioned complexing agents. Complexing agents can advantageously bind metal ions that impair the stability of the medical product. Furthermore, complexing agents have the advantage of increasing the stability of the medical product against microorganisms.

The complexing agent preferably has a proportion of 0.001 wt.% to 10 wt.%, in particular 0.01 wt.% to 5 wt.%, preferably 0.01 wt.% to 1 wt.%, based on the total weight of the medical device, the thread or threads, preferably the coating or composition of the medical device, the thread or threads.

For the purposes of the present invention, the term “film former” is understood to mean a macromolecular or low-molecular substance, preferably a polymer, in particular a long- or short-chain polymer, which ensures the formation of a coherent film in a coating material.

In principle, the film former can be a hydrophilic film former and/or a hydrophobic film former.

Preferably, the film former is selected from the group consisting of polyvinylpyrrolidone, compounds derived from polyvinylpyrrolidone (e.g. styrene/vinylpyrrolidone copolymer, vinylpyrrolidone/eicosene copolymer or vinylpyrrolidone/dimethylaminoethyl methacrylate copolymer), polyvinyl alcohol, polyethylene glycols, polysaccharides, chitosan, chitosan oligomers, chitosan derivatives, cellulose derivatives, hypromellose, polyacrylic acids, polyurethane, polyquaternium compounds, copolymers of vinylpyrrolidone and vinyl acetate, protein hydrolysates, proteins (such as sericin), natural resins, shellac, rosin, benzoin, sandarac and combinations, in particular mixtures, of at least two of the aforementioned film formers.

The film former preferably has a proportion of 0.001 wt.% to 10 wt.%, in particular 0.01 wt.% to 5 wt.%, preferably 0.01 wt.% to 2 wt.%, based on the total weight of the medical device, the thread or threads, preferably the coating or composition of the medical device, the thread or threads.

Furthermore, the composition can comprise a solvent, in particular an organic solvent, preferably selected from the group consisting of alcohol, ketone, ether, ester and combinations, in particular mixtures, of at least two of the aforementioned solvents. The alcohol can be a monohydric alcohol and/or dihydric alcohol and/or trihydric alcohol, in particular having two to ten carbon atoms, preferably two to eight carbon atoms. The alcohol is preferably selected from the group consisting of methanol, ethanol, propan-1-ol, propan-2-ol, propan-1,2-dipl, propan-1,3-diol, propan-1,2,3-triol, butane-1,3-diol, pentane-1,2-diol, hexane-1,2-diol, octane-1,2-diol, decane-1,2-diol, hexane-1,2-diol, octane-1,2-diol and combinations, in particular mixtures, of at least two of the aforementioned alcohols. The ketone can in particular have three to eight carbon atoms. For example, the ketone can be butan-2-one. The ether can be, for example, tetrahydrofuran. The ester can in particular be a carbonic acid ester, such as diethyl carbonate, and/or carboxylic acid ester, such as ethyl acetate.

The solvent may have a proportion of 0.001 wt.% to 95 wt.%, in particular 0.01 wt.% to 90 wt.%, preferably 0.01 wt.% to 70 wt.%, based on the total weight of the composition.

Alternatively, the composition may be free or substantially free of a solvent, in particular organic solvent, preferably an alcohol and/or ketone and/or ether and/or ester. The term “substantially free” in this context means that the composition has a solvent content of < 5 wt.% and > 0 wt.%, in particular < 4 wt.% and > 0 wt.%. preferably < 3 wt.% and > 0 wt.%, in particular < 2 wt.% and > 0 wt.%, in particular < 1 wt.% and > 0 wt.%, based on the total weight of the composition.

Furthermore, the medical device, the thread or the threads, preferably the coating or composition of the medical device, the thread or the threads, can further comprise a polyethylene glycol, polypropylene glycol or a mixture containing or consisting of polyethylene glycol and polypropylene glycol.

Furthermore, the medical device, the thread or threads, preferably the coating or composition of the medical device, the thread or threads, can also contain an acid, in particular for adjusting the pH value. The acid can be an inorganic acid and/or organic acid. The acid is preferably selected from the group consisting of hydrochloric acid, formic acid, acetic acid, glycolic acid, lactic acid, gluconic acid, gluconodeltalactone, malic acid, tartaric acid and combinations, in particular mixtures, of at least two of the aforementioned acids.

The acid can have a proportion of 0.001 wt.% to 10 wt.%, in particular 0.01 wt.% to 5 wt.%, preferably 0.01 wt.% to 2 wt.%, based on the total weight of the antimicrobially active product, preferably the coating or composition of the medical device, the thread or threads.

Furthermore, the medical device, the thread or threads, preferably the coating or composition of the medical device, the thread or threads, can also contain an alkali or base for setting a pH value that is compatible with the skin, mucous membrane or wound. The alkali or base can be selected from the group consisting of sodium hydroxide, potassium hydroxide, calcium hydroxide, magnesium hydroxide, ammonium hydroxide, organic amines and combinations, in particular mixtures, of at least two of the aforementioned alkalis or bases.

The organic amines can in particular be selected from the group consisting of monoethanolamine, triethanolamine, 2-amino-2-methyl-1-propanol, tetrahydroxypropylethylenediamine, tromethamine, monoisopropanolamine, triisopropanolamine and combinations, in particular mixtures, of at least two of the aforementioned organic amines.

Furthermore, the medical device, the thread or the threads, preferably the coating or composition of the medical device, the thread or the threads, can also comprise water, in particular purified water or water for injection purposes.

In particular, the water can have a proportion of 0.01 wt.% to 99.99 wt.%, in particular 0.1 wt.% to 99.9 wt.%, preferably 0.1 wt.% to 99.8 wt.%, based on the total weight of the coating or composition of the medical device, the thread or threads. In particular, the components of the coating or composition of the medical device, the thread or threads can be supplemented with water to 100 wt.%.

In a further embodiment of the invention, the medical device, the thread or the threads comprise an in vivo degradable and/or in vivo resorbable material or the medical device, the thread or the threads consist of an in vivo degradable and/or in vivo resorbable material.

The expression "in vivo degradable material" refers in the sense of the present invention to a material that can be metabolized in a human or animal body, in particular under the action of enzymes. The degradation of the material can proceed completely up to mineralization, i.e. release of chemical elements and their incorporation into inorganic compounds such as carbon dioxide, oxygen and/or ammonia, or it can remain at the stage of degradation-stable intermediate or transformation products.

The term “in vivo resorbable material” in the sense of the present invention refers to a material that can be taken up in a human or animal body by living cells or living tissue, such as kidneys, without degradation or significant degradation of the material taking place.

Preferably, the in vivo degradable and/or in vivo resorbable material is a polymer.

In particular, the in vivo degradable and/or in vivo resorbable material can be selected from the group consisting of polyhydroxyalkanoates or polyhydroxyalkanoic acids, proteins, extracellular proteins, serum proteins, polysaccharides, mucopolysaccharides, polysaccharides carrying carboxyl groups, polysaccharides carrying amino groups, polysaccharides carrying aldehyde groups, copolymers thereof, salts thereof, stereoisomers, in particular diastereomers, thereof and combinations, in particular mixtures or blends, of at least two of the aforementioned in vivo degradable and/or in vivo resorbable materials.

Preferably, the in vivo degradable and/or in vivo resorbable material is selected from the group consisting of polyglycolide or polyglycolic acid, polylactide or polylactic acid, polydioxanone, poly-3-hydroxybutyrate or poly-3-hydroxybutyric acid, poly-4-hydroxybutyrate or poly-4-hydroxybutyric acid, polytrimethylene carbonate, poly-ε-caprolactone, polyvinyl alcohol, cotton, cellulose, cellulose derivatives, alkylcelluloses, methylcellulose, hydroxyalkylcelluloses, hydroxymethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, carboxyalkylcelluloses, carboxymethylcellulose, starch, amylose, amylopectin, dextran, dextrin, chitin, chitosan, hyaluronic acid, dextran sulfate, heparin, heparan sulfate, chondroitin sulfate, dermatan sulfate, collagen, gelatin, elastin, reticulin, fibronectin, laminin, fibrin, Fibrinogen, albumin, copolymers thereof, salts thereof, stereoisomers, in particular diastereomers, thereof and combinations, in particular mixtures or blends, of at least two of the aforementioned in vivo degradable and/or in vivo resorbable materials.

The copolymers mentioned in the previous paragraph can in particular be a copolymer having or consisting of lactide units, in particular L-lactide units, and glycolide units, in particular with a proportion of 10% by weight of lactide units, in particular L-lactide units, and 90% by weight of glycolide units, each based on the total weight of the copolymer. Alternatively, the copolymers mentioned in the previous paragraph can be a copolymer having or consisting of trimethylene carbonate units and glycolide units or of glycolide units, trimethylene carbonate units and 6-hydroxycaproic acid units.

In a further embodiment of the invention, the medical device, the thread or the threads comprise a material that is not degradable in vivo and/or not resorbable in vivo, or the medical device, the thread or the threads consist of a material that is not degradable in vivo and/or not resorbable in vivo.

Preferably, the in vivo non-degradable and/or in vivo non-resorbable material is a polymer.

In particular, the in vivo non-degradable and/or in vivo non-resorbable material can be selected from the group consisting of polyolefins, polyamides, polyesters, polyurethanes, thermoplastic polyurethanes, copolymers thereof and combinations, in particular mixtures or blends, of at least two of the aforementioned in vivo non-degradable and/or in vivo non-resorbable materials.

Preferably, the in vivo non-degradable and/or in vivo non-resorbable material is selected from the group consisting of polyethylene, low density polyethylene, high density polyethylene, high molecular weight polyethylene, ultra-high molecular weight polyethylene, polypropylene, polyethylene terephthalate, polypropylene terephthalate, polybutylene terephthalate, polyacrylonitrile, polyamide 6, polyamide 6-6, polyamide 6-12, polyamide 12, silk, rayon, natural silk, polytetrafluoroethylene, expanded polytetrafluoroethylene (ePTFE), polyvinylidene difluoride, polytetrafluoropropylene, polyhexafluoropropylene, polyurethane, copolymers thereof and combinations, in particular mixtures or blends, of at least two of the aforementioned in vivo non-degradable and/or in vivo non-resorbable materials.

Furthermore, the medical device or the thread can be designed as a monofilament, pseudomonofilament, multifilament or core-sheath thread or the threads can be designed as monofilaments, pseudomonofilaments, multifilaments or core-sheath threads. The term "core-sheath thread" in the sense of the present invention is to be understood as a thread with a thread core and a thread sheath that at least partially, in particular only partially or completely, i.e. continuously, surrounds the thread core. With regard to suitable materials for the thread core and the thread sheath, reference is made to the previously mentioned in vivo degradable or in vivo resorbable as well as in vivo non-degradable or in vivo non-resorbable materials.

Furthermore, the medical device or the thread or threads or the coating, in particular in the form of an outer final coating of the medical device, the thread or threads or an outer layer of the coating, or the composition of the medical device, the thread or threads, can comprise an additive, in particular a further active ingredient and/or dye, in addition to the dihydrotriazine compound, the tautomer thereof or the salt thereof. The additive can in particular be selected from the group consisting of antimicrobial, in particular antibiotic, active ingredient, wound healing-promoting active ingredient, disinfectant active ingredient, anti-inflammatory active ingredient, blood coagulation-promoting active ingredient, growth factors, cell differentiating factors, cell adhesive factors, cell recruiting factors, cell receptors, cell binding factors, cytokines, peptides, structural proteins, extracellular proteins such as collagen, serum proteins such as albumin, polysaccharides such as hyaluronic acid, oligonucleotides, polynucleotides, DNA, RNA, salts thereof, stereoisomers, in particular diastereomers thereof, fatty acids, alkali metal fatty acid salts, alkaline earth metal fatty acid salts (such as calcium stearate), anthraquinone dyes, azo dyes, dioxazine dyes, indigoid dyes, metal complex dyes, formazan dyes, phthalocyanine dyes, methine dyes and combinations, in particular Mixtures of at least two of the abovementioned additives.

A suitable anthraquinone dye is, for example, the dye 1-hydroxy-4-(4-methylanilino)anthracene-9,10-dione, which is also known under the name D&C Violet No. 2.

Furthermore, the thread or threads can have a cornerless, in particular circular, oval or elliptical, cross-section.

Alternatively, the thread or threads may have an angular, in particular triangular, quadrangular such as square or rectangular, pentagonal, hexagonal, heptagonal, octagonal, nonagonal, decagonal or star-shaped cross-section.

Furthermore, the medical device or the threads can be in the form of a woven fabric, a knitted fabric, a nonwoven fabric or a nonwoven material.

Furthermore, the medical device can be designed as a one-dimensional or elongated, in particular thread-like, textile product.

Furthermore, the medical device can be designed as a textile fabric.

Furthermore, the medical device can be designed as a three-dimensional, particularly tubular, textile product.

In a further embodiment of the invention, the medical device is an implant, in particular a surgical implant.

In a further embodiment of the invention, the medical device is designed as a wound care material, in particular surgical suture material or surgical suture thread.

In a further embodiment of the invention, the medical device is designed as a mesh, preferably a surgical mesh.

The net can have openings, in particular meshes or pores, with a clear width of 0.2 mm to 5 mm, in particular 0.2 mm to 4 mm. The term "clear width" in the sense of the present invention is to be understood as the inner diameter of openings, in particular meshes or pores, of the net.

Furthermore, the net can have a basis weight of 25 g/m ² to 90 g/m ² , in particular 25 g/m ² to 75 g/m ² , preferably 25 g/m ² to 60 g/m ² .

For example, the net may be a net comprising or consisting of monofilament polypropylene with a basis weight of 36 +/- 5 g/m ² , a mesh size of approximately 1 mm and a mesh density of approximately 112 meshes per cm ² . Such a net is sold commercially by the applicant under the name Optilene® Mesh LP.

Furthermore, the mesh can be, for example, a mesh comprising or consisting of monofilament polypropylene with a basis weight of 48 +/- 7 g/m ² , a mesh size of 3.6 × 2.8 mm and a mesh density of approximately 60 meshes per cm ² . Such a mesh is sold commercially by the applicant under the name Optilene® Mesh Elastic. The mesh is preferably a mesh for implantation and/or reinforcement and/or surgical repair of weak, damaged or torn soft tissue.

Furthermore, the mesh can preferably be a mesh for plastic and/or reconstructive abdominal surgery and/or reinforcement of muscle valves and/or repair of hernias. The hernias can in particular be abdominal, inguinal, femoral, lower leg, diaphragmatic, scrotal, umbilical or incisional hernias.

Furthermore, the mesh can preferably be a mesh for supporting pelvic organs and/or for reconstructing the pelvic floor, in particular in the transvaginal region, and/or for supporting the rectum and/or the urethra.

Preferably, the mesh, in particular surgical mesh, is selected from the group consisting of hernia mesh and prolapse mesh.

Furthermore, the medical device, thread or threads can be manufactured under controlled hygienic conditions or aseptically in a clean room.

In particular, the medical device, thread or threads may be in sterilized form. For example, the medical device, thread or threads may be sterilized by gamma irradiation, beta irradiation, plasma sterilization, steam sterilization or sterilization with ethylene oxide.

According to a second aspect, the invention relates to a method for producing the medical product according to the first aspect of the invention, wherein the dihydrotriazine compound of the general formula I, the tautomer thereof or the salt thereof, in particular as a component of a composition, is mixed with a material that is degradable in vivo and/or resorbable in vivo and/or non-degradable in vivo and/or non-resorbable in vivo to form a mixture and the mixture is then shaped into the medical product, in particular extruded, spun, pressed, rolled, cast or blown. The mixture is preferably spun in the form of a thread or a plurality of threads. Suitable spinning techniques include all methods familiar to the person skilled in the art, in particular melt, gel, solution or dry spinning. The spun thread or threads can be further processed into either a surgical suture material or surgical sewing thread, a surgical mesh or another textile medical product. In this regard, reference is made to the previous description.

With regard to further features and advantages of the method, in particular with regard to the medical device, the thread or threads, the dihydrotriazine compound of the general formula I or the tautomer thereof or the salt thereof, the composition, the material degradable in vivo and/or resorbable in vivo and the material non-degradable in vivo and/or non-resorbable in vivo, reference is made in full to the corresponding statements made under the first aspect of the invention, which also apply mutatis mutandis to the method according to the second aspect of the invention.

1. a) Aufbringen der Dihydrotriazinverbindung der allgemeinen Formel I, des Tautomers davon oder des Salzes davon, insbesondere als Bestandteil einer Zusammensetzung, auf ein Medizinprodukt, insbesondere auf eine Oberfläche eines Medizinprodukts.

According to a third aspect, the invention relates to a method for producing the medical device according to the first aspect of the invention, comprising the following step:

1. a) Applying the dihydrotriazine compound of the general formula I, the tautomer thereof or the salt thereof, in particular as a component of a composition, to a medical device, in particular to a surface of a medical device.

For this purpose, the composition mentioned in the previous paragraph can be in the form of a solution, in particular an aqueous solution, a suspension, in particular an aqueous suspension, a gel, in particular a hydrogel, or a powder.

Furthermore, step a) can be carried out, for example, by dipping, spraying, brushing, coating or soaking.

With regard to further features and advantages of the method, in particular with regard to the medical device, the dihydrotriazine compound of the general formula I or the tautomer thereof or the salt thereof and the composition, reference is made in full to the corresponding statements made under the first aspect of the invention, which also apply mutatis mutandis to the method according to the third aspect of the invention.

Further features and advantages of the invention emerge from the following description of preferred embodiments. Individual features can be implemented individually or in combination with one another. The described embodiments serve only to further explain the invention without limiting it thereto.

EXAMPLE PART

1. 1. A braided multifilament thread made of glycolide was soaked in a dip bath with a solution consisting of the following components:

Femotaxidine (gluconate) 0.500 wt.% Polyvinylpyrrolidone 5,000 wt.% Caprylic/capramidopropyl betaine (35%) 3,500 wt.% Propan-2-ol 40.00 wt.% Purified water 51.00 wt.%

The coated material was dried under controlled conditions, packed in a Tyvek bag under controlled conditions, sealed and sterilized by fumigation with ethylene oxide.

2. A braided multifilament thread made of Polyglactin 910 was soaked in a dip bath with a solution consisting of the following components: Femotaxidine (gluconate) 0.500 wt.% Poloxamer 1,500 wt.% Propan-2-ol 40.00 wt.% Purified water 58.00 wt.%

The coated material was dried under controlled conditions, packed in a Tyvek bag under controlled conditions, sealed and sterilized by fumigation with ethylene oxide.

3. A braided multifilament thread made of Polyglactin 910 was soaked in a dip bath with a solution consisting of the following components: Femotaxidine (gluconate) 2,000 wt.% Propan-2-ol 40.00 wt.% Purified water 58.00 wt.%

The coated material was dried under controlled conditions, packed in a Tyvek bag under controlled conditions, sealed and sterilized either by gassing with ethylene oxide or by gamma irradiation.

4. A braided multifilament thread made of Polyglactin 910 was soaked in a dip bath with a solution consisting of the following components: Femotaxidine (gluconate) 2,000 wt.% Ethanol 98.00 wt.%

The coated material was dried under controlled conditions, packed in a Tyvek bag under controlled conditions, sealed and sterilized either by gassing with ethylene oxide or by gamma irradiation.

5. A monofilament thread made of poly-4-hydroxybutyrate was soaked in a dip bath with a solution consisting of the following components: Femotaxidine (gluconate) 0.200 wt.% Chitosan oligomer 5 kDa 1,000 wt.% acetic acid 0.200 wt.% Propan-2-ol 20.00 wt.% Purified water 78.60 wt.%

The coated material was dried under controlled conditions, packed in a Tyvek bag under controlled conditions, sealed and sterilized using a plasma process.

6. A mesh (Optilene ^® Mesh LP) was soaked in a dip bath with a solution consisting of the following components: Femotaxidine (gluconate) 0.500 wt.% Polyvinylpyrrolidone 5,000 wt.% Caprylic/capramidopropyl betaine (35%) 3,500 wt.% Propan-2-ol 40.00 wt.% Purified water 51.00 wt.%

The coated net was dried under controlled conditions, packed in a Tyvek bag under controlled conditions, sealed and sterilized by fumigation with ethylene oxide.

7. A mesh (Optilene ^® Mesh Elastic) was soaked in a dip bath with a solution consisting of the following components: Femotaxidine (gluconate) 0.500 wt.% Poloxamer 1,500 wt.% Propan-2-ol 40.00 wt.% Purified water 58.00 wt.%

The coated net was dried under controlled conditions, packed in a Tyvek bag under controlled conditions, sealed and sterilized by fumigation with ethylene oxide.

QUOTES INCLUDED IN THE DESCRIPTION

This list of documents listed by the applicant was generated automatically and is included solely for the better information of the reader. The list is not part of the German patent or utility model application. The DPMA accepts no liability for any errors or omissions.

Cited patent literature

• EP 2359874 B1 [0006]
• EP 1574503 A1 [0010]
• WO 2020108880 A1 [0011]
• WO 2020108881 A1 [0012]

Cited non-patent literature

• doi: 10.1128/AAC.45.2.428-432.2001 [0007]
• https://bmcmicrobiol.biomedcentral.com/articles/10.1186/s12866-015-0523-4 [0008]

Claims (15)

Medical device comprising a thread or a plurality of threads, characterized in that the medical device comprises a dihydrotriazine compound of the following general formula I, a tautomer thereof or a salt thereof:

wherein - R ₁ (i) represents a phenyl group or a phenylalkyl group, each of which is optionally substituted by 1 to 3 substituents selected from the group consisting of C _1-6 alkoxy group, hydroxy group, a halogen atom, C _1-6 haloalkyl group, C1-6 alkyl group, a sulfonamido group and C _1-6 haloalkoxy group, (ii) represents a naphthyl group or a naphthylalkyl group, (iii) a heterocyclic group, a heterocyclic alkyl group or a heterocyclic aminoalkyl group, (iv) an alkyl group having 1 to 16 carbon atoms or (v) a cycloalkyl group or a cycloalkylalkyl group, - R ₁ ' represents a hydrogen atom bonded to the nitrogen atom at position 1 or 3 of the dihydrotriazine ring, - R ₂ and R ₃ independently represent a hydrogen atom or a methyl group, - R ₄ represents an alkyl group having 7 to 16 carbon atoms and - the dashed line indicates that the position of a double bond is either between positions 1 and 2 or between positions 2 and 3 of the dihydrotriazine ring. Medical device according to Claim 1 , characterized in that R ₁ represents a phenyl group or a phenylalkyl group, in particular benzyl group, each of which is optionally substituted by 1 to 3 substituents selected from the group consisting of fluorine atom, chlorine atom, hydroxy group, methyl group, tert-butyl group, trifluoromethyl group and methoxy group, R ₁ ' represents a hydrogen atom bonded to the nitrogen atom at position 1 or 3 of the dihydrotriazine ring, R ₂ and R ₃ each represent a methyl group and R ₄ represents an n-octyl group, n-nonyl group or n-decyl group. Medical device according to Claim 1 or 2 , characterized in that R ₁ represents a phenyl group, 4-chlorophenyl group, 2,4-difluorophenyl group, 2,3,4-trifluorophenyl group, 4-tert-butylphenyl group, 4-methoxyphenyl group, 2-methoxy-4-tert-butylphenyl group, 4-trifluoromethoxyphenyl group, benzyl group, methylbenzyl group, 4-methylbenzyl group, 4-methoxybenzyl group, 3,4-dimethoxybenzyl group, 4-hydroxybenzyl group, 3,4-dichlorobenzyl group, 2,3,4-trichlorobenzyl group, 4-trifluoromethylbenzyl group, 1-phenylethyl group, 2-phenylethyl group, 1-phenylpropyl group, 2-phenylpropyl group or 3-*phenylpropyl group, preferably a 4-methylbenzyl group, R ₁ ' represents a hydrogen atom which is bonded to the nitrogen atom at position 1 or 3 of the dihydrotriazine ring, R ₂ and R ₃ each represent a methyl group and R ₄ represents an n-octyl group, n-nonyl group or n-decyl group. Medical device according to one of the preceding claims, characterized in that R ₁ represents a methylbenzyl group, preferably 4-methylbenzyl group, and/or R ₂ and R ₃ each represent a methyl group and/or R ₄ represents an n-octyl group. Medical device according to one of the preceding claims, characterized in that R ₁ represents a methylbenzyl group, preferably 4-methylbenzyl group, R ₁ ' represents a hydrogen atom which is bonded to the nitrogen atom at position 1 or 3 of the dihydrotriazine ring, R ₂ and R ₃ each represent a methyl group and R ₄ represents an n-octyl group. Medical device according to one of the preceding claims, characterized in that the dihydrotriazine compound of the general formula I or the salt thereof is 4-octylamino-1,6- dihydro-6,6-dimethyl-2-(4'-methylbenzylamino)-1,3,5-triazine gluconate, 4-octylamino-3,6-dihydro-6,6-dimethyl-2-(4'-methylbenzylamino)-1,3,5-triazine gluconate or a tautomer thereof. Medical device according to one of the preceding claims, characterized in that the dihydrotriazine compound, the tautomer thereof or the salt thereof is dispersed in the thread or threads. Medical device according to one of the Claims 1 until 6 , characterized in that the dihydrotriazine compound, the tautomer thereof or the salt thereof forms a coating or a component of a coating of the thread or threads. Medical device according to one of the preceding claims, in particular Claim 8 , characterized in that the thread or threads, in particular the coating of the thread or threads, further comprises at least one further component, in particular selected from the group consisting of surface-active compound, complexing agent, film former and combinations of at least two of the aforementioned components. Medical device according to one of the preceding claims, characterized in that - the at least one surface-active compound is selected from the group consisting of poloxamer, fatty alcohol alkoxylate, polyvinylpyrrolidone, alkylpolyglucoside, alkylbetaine, alkylamidoalkylbetaine, distearyldimethylammonium chloride, didecyldimethylammonium chloride, cetyltrimethylammonium chloride, cetyltrimethylammonium bromide, cetylpyridinium chloride, mecetronium ethyl sulfate and combinations of at least two of the aforementioned surface-active compounds and/or - the at least one complexing agent is selected from the group consisting of citric acid, tartaric acid, succinic acid, methylglycine diacetate, ethyldiaminetetraacetate, N,N'-bis-(carboxymethyl)-L-glutamate, polyaspartic acid, iminodisuccinate, phosphonates, phosphonobutanetricarboxylic acid, lauryl alcohol diphosphonic acid, editronic acid, salts of the aforementioned Complexing agents and combinations of at least two of the aforementioned complexing agents and/or the at least one film former is selected from the group consisting of polyvinylpyrrolidone, compounds derived from polyvinylpyrrolidone, polyvinyl alcohol, polyethylene glycols, polysaccharides, chitosan, chitosan oligomers, chitosan derivatives, cellulose derivatives, hypromellose, polyacrylic acids, polyurethane, polyquaternium compounds, copolymers of vinylpyrrolidone and vinyl acetate, protein hydrolysates, proteins, natural resins, shellac, rosin, benzoin, sandarac and combinations of at least two of the aforementioned film formers. Medical device according to one of the preceding claims, characterized in that the thread or threads comprise an in vivo degradable and/or in vivo resorbable material, preferably selected from the group consisting of polyhydroxyalkanoates or polyhydroxyalkanoic acids, proteins, extracellular proteins, serum proteins, polysaccharides, mucopolysaccharides, polysaccharides carrying carboxyl groups, polysaccharides carrying amino groups, polysaccharides carrying aldehyde groups, copolymers thereof, salts thereof, stereoisomers, in particular diastereomers, thereof and combinations of at least two of the aforementioned in vivo degradable and/or in vivo resorbable materials. Medical device according to one of the preceding claims, characterized in that the thread or threads comprise an in vivo non-degradable and/or in vivo non-resorbable material, preferably selected from the group consisting of polyolefins, polyamides, polyesters, polyurethanes, thermoplastic polyurethanes, copolymers thereof and combinations of at least two of the aforementioned in vivo non-degradable and/or in vivo non-resorbable materials. Medical device according to one of the preceding claims, characterized in that the medical device is an implant, in particular a surgical implant. Medical device according to one of the preceding claims, characterized in that the medical device is designed as a wound care material, in particular surgical suture material or surgical sewing thread. Medical device according to one of the preceding claims, characterized in that the medical device is designed as a surgical mesh, preferably selected from the group consisting of hernia mesh and prolapse mesh.