EP2265648A1

EP2265648A1 - Hydrolytically decomposable ionic copolymers

Info

Publication number: EP2265648A1
Application number: EP09733031A
Authority: EP
Inventors: Andreas Greiner; Seema Agarwal; Thomas Kissel; Liqun Ren
Original assignee: Philipps Universitaet Marburg
Current assignee: BASF SE
Priority date: 2008-04-14
Filing date: 2009-04-09
Publication date: 2010-12-29
Also published as: WO2009127600A1; US20110160426A1; US9068065B2

Abstract

The present invention provides novel hydrolytically decomposable ionic copolymers. These ionic copolymers are made up of a cyclic ketene acetal A, an anionic or cationic methacrylic acid derivative B selected from 2-methyl-methacrylate, [2-(2-methyl-1-methylen-allyloxy)-ethane sulfonate, [2-(2-methyl-1-methylen-allyloxy)ethyl]-phosphonate or a quaternary amine of N,N-dimethylaminoethylmethacrylic acid (DMAEMA) and optionally a neutral methacrylic acid derivative C. According to the invention, hydrolytically decomposable ionic copolymers are produced by polymerizing the components A, B and C in the presence of a radical starter under a protective gas atmosphere, followed by purification. All copolymers according to the invention are hydrolytically decomposable. Copolymers containing a maximum of 40 mol-% of ester groupings in the backbone are also biodegradable, wherein in the case of cationic copolymers a maximum of 20 mol-% quaternized DMAEMA may be present. Cationic copolymers containing at least 50 mol-% of component B are antimicrobial. Both anionic as well as cationic copolymers are suitable for the production of nanoparticles. Cationic copolymers can be used a superhydrophobic materials as well as adhesives. Anionic copolymers are suitable as biodegradable thermoplastic elastomers and as biodegradable ionomers.

Description

Patent application

Hydrolytically degradable ionic copolymers

The present invention provides novel, hydrolytically degradable ionic copolymers. These copolymers are composed of a cyclic ketene acetal, an anionic or cationic Methacrylsäuredehvat and optionally another Methacrylsäuredehvat. These ionic di- and terpolymers are prepared by radical polymerization of the starting monomers in the presence of a radical initiator under a protective gas atmosphere.

Description and introduction of the general field of the invention

The present invention relates to the fields of macromolecular chemistry, polymer chemistry, biopharmacy and materials science.

State of the art

The present invention relates to hydrolytically degradable copolymers of cyclic ketene acetals and methacrylic acid derivatives. The copolymers according to the invention contain ester groups in the polymer backbone as well as ionic groups in the side chains.

It is known that polymers whose carbon backbone is interrupted by functional groups such as ester, amide, carbonate, urethane or ether groups and whose hydrocarbon moieties between the functional groups are predominantly aliphatic in nature can be degraded by microorganisms. This is described, for example, in SH Huang, Encyclopaedia of Polymer Sciences Vol. 2, 220-242. Polyolefins with a pure carbon backbone however, are resistant to microbial attack. An exception is, for example, polyvinyl alcohol which, after oxidative cleavage, is completely degraded to carbon dioxide and water (T. Suzuki et al., J Appl Polym Sci, Polym Symp. 35 (1973), 431). Polyvinyl acetate, on the other hand, is only degraded with difficulty because it must first of all be hydrolyzed to polyvinyl alcohol.

From JP 02214719 A polymers of olefins, acrylic esters, vinyl esters and styrenes with 2-methylene-1, 3-Dioxepan are known as hydrolyzable polymers for use in marine paints.

DE 39 30 097 A1 describes UV-crosslinkable copolymers of cyclic olefinically unsaturated ring-opening polymerizing monomers, olefinically unsaturated monomers, preferably olefinically unsaturated esters, and copolymerizable olefinically unsaturated acetophenone or benzophenone derivatives. These polymers are suitable as coating, impregnating and adhesive agents, in particular as pressure-sensitive adhesives.

DE 43 07 759 C1 describes biodegradable copolymers of vinyl esters with cyclic ketene acetals. However, the copolymers are not ionic.

US 6,534,610 B1 discloses biodegradable copolymers of a first monomer from the group of olefins and a second monomer which contains a hydrolytically cleavable group, for example an acetal, a ketal, an ester or an imide. In this case, the hydrolyzable groups of the copolymer according to the invention are exclusively in the main chain and never in a side chain. According to the teaching of US Pat. No. 6,534,610 B1, copolymers are more readily degradable if the hydrolytically cleavable groups are located exclusively in the main chain. The copolymers are prepared by transition metal-catalyzed polymerization, preferably in the presence of metallocene or Brookhart catalysts.

EP 1 267 953 B1 describes compositions of crosslinkable prepolymers for biodegradable implants. The invention relates in particular to crosslinked polyester, polyorthoesters and polyacetal prepolymers which are suitable as in situ implants for bone and periodontal cavities.

Copolymers of cyclic, ring-opening ketene acetals and acrylic acid derivatives are known in the art. However, so far there are no such copolymers, which also contain ionic groups.

Thus, Wickel et al. in Macromolecules 2003, 36, 2397-2403 homopolymers and random copolymers of 5,6-benzo-2-methylene-1, 3-dioxepan and methyl methacrylate. Ren and Agarwal in Macrom Chem Phys 2007,208, 245-253 describe coesters of 5,6-benzo-2-methylene-1,3-dioxepan and N-isopropylacrylamide. The hydrolytic and enzymatic degradation of terpolymers of two different PEG methacrylates and 5,6-benzo-2-methylene-1,3-dioxepane is described in Lutz et al., Macromolecules 2007, 40, 8540-8543. However, in all three works mentioned no ionic copolymers are described.

In contrast, the present invention provides novel copolymers having biodegradable ester moieties in the polymer backbone and ionic groups in the side chains. The starting point is the known process of introducing ester groups into a polyvinyl polymer backbone by means of a combination of free-radical polymerization and free-radical ring-opening polymerization. The novel introduction of ionic groups into the side chains surprisingly ionic copolymers have been found with new properties: The ionic copolymers of the invention are very readily biodegradable, and by the ionic groups in the side chains they have compared to the known copolymers of dioxepans and Acrylsäuredehvaten new, surprising Properties. task

The object of the present invention is to provide hydrolytically degradable polyionic compounds which have ionic groups in the side chains and ester groups in the polymer backbone and in the side chains, as well as processes for the preparation of these hydrolytically degradable polyionic compounds.

Solution of the task

The object of providing hydrolytically degradable polyionic compounds is inventively achieved by polyionic Copolymehsate which are composed of a) 10 to 55 mol% of a cyclic ketene acetal A, b) 4 to 90 mol% of a methacrylic acid derivative B, c) 0 to 80% Mol% of a methacrylic acid derivative C, wherein the sum of the components A, B and C is 100 mol%, and wherein

the cyclic ketene acetal A is selected from

2-methylene-1,3-dioxane

2-M ethylene-1, 3-dioxepane (III) (MDO)

5,6-Benzo-2-methylene-1,3-dioxepane

(I) (BMDO)

(I ")

2-methylene-1,3-dioxolane

4,5-dialkyl-2-methylene

5,6-dialkyl-2-methylene-1,3-dioxolane 1,3-dioxepane (V)

(VI)

(IV)

wherein R ¹ and R ² independently of one another represent a linear or branched alkyl group having 1 to 12 carbon atoms,

and the methacrylic acid derivative B is selected from 2-methyl-methacrylate (VII)

M

[2- (2-methyl-1-methylene-allyloxy)] ethanesulfonate (VIII)

[2- (2-Methyl-1-methylene-allyloxy) ethyl] -phosphonate (IX)

where M ^{+ represents} a lithium, sodium, potassium, ammonium or tetraalkylammonium cation and the polyionic copolymer is an anionic copolymer,

N, N-Dimethylaminoethylmethacrylic acid (DMAEMA) according to formula (Xa)

wherein 45% to 95% of DMAEMA is ionized in the form of a quaternary amine of formula (Xb), so that it is a cationic Copolymehsat polyionic copolymer, wherein

R ^{3 is} a linear or branched alkyl group having 1 to 12 carbon atoms or a benzyl group of the formula (XI)

with n = 0-12 and X ^"is fluoride, chloride or bromide,

and wherein the methacrylic acid derivative C is selected from compounds of the formula (XII)

wherein R is selected from

-OCH ₃ , -N (CH ₃ ) ₂ , an oligoethylene glycol of the general formula -O- (CH ₂ -CH ₂ -O) _m H, a co-methoxy-oligoethylenglykol the general formula -O- (CH ₂ -CH ₂ -O) _m -CH ₃ , where m is a natural number between 1 and 12, Vinyl acetate, acrylonitrile, 2-hydroxyethyl methacrylate, N-vinylformamide, N-vinylacetamide, N-methyl-N-vinylacetamide, N-vinylcaprolactam, N-vinylpyrrolidone, N-2-hydroxypropylmethacrylamide, N-3-hydroxypropylmethacrylamide, N, N Dimethylacrylamide, styrene, N, N-dimethylaminostyrene.

Surprisingly, it has been found that the copolymers according to the invention which have ionic groups in the side chains and ester groups in the polymer backbone and in the side chains are hydrolytically degradable. The ionic groups may be cationic or anionic groups.

In the context of the present invention, "copolymer" is understood to mean those polymers which contain a plurality of types of monomer Accordingly, the products of the reaction of several types of monomer are referred to as "copolymers".

By "hydrolytically degradable" is meant that the ionic copolymers of the present invention contain a hydrolyzable moiety in the polymer backbone that allows the copolymers to be broken down into smaller degradation products when exposed to water.

By "cationic" moieties are meant organic cations, in the present invention they are quaternary ammonium moieties. "Anionic" moieties refer analogously to organic anions, which in the context of the present invention are methacrylates, sulfonates and phosphonates.

The ionic groups are based on uncharged amino, methacrylic acid, sulfonic acid or phosphonic acid groups. These groups are ionizable, i. they can be converted into the corresponding cations or anions.

According to the invention, the ionic and / or ionizable groups are located in the side chain of the copolymers according to the invention. By "ionic groups" it is meant that the methacrylic acids, sulfonic acids, phosphoric acids or amino groups are present in the form of their corresponding salts In the case of methacrylic acids, sulfonic acids and phosphonic acids, these corresponding salts are tetraalkylamines, lithium, sodium and potassium In the case of N, N-dimethylaminoethyl methacrylic acid (DMAEMA), the corresponding ionic groups are quaternary ammonium salts of the formula (Xb).

Accordingly, "ionisable groups" are uncharged methacrylic acid, sulfonic acid, phosphonic acid and N, N-dimethylaminomethacrylic acid groups.

Copolymers according to the invention which contain ionic groups as defined above are also referred to below as "ionic copolymers", and in an analogous manner hereinafter also referred to as "ionic copolymers".

If the ionic and / or ionizable groups are amino groups or their corresponding quaternary amines, the copolymers or copolymers are referred to as "cationic copolymers" or "cationic copolymers". If the ionic and / or ionizable groups are methacrylic acids, sulfonic acids or phosphoric acid or their corresponding salts, the copolymers or copolymers are referred to as "anionic copolymers" or "anionic copolymers".

The polyionic copolymers of the invention are electrically neutral to the outside, since the charge of the ionic groups is compensated by oppositely charged ions. In the case of quaternary ammonium moieties, the counterions are preferably halides selected from fluoride, chloride and bromide. In the case of methacrylic acids, sulfonic acids or phosphonic acids, the counterions are preferably lithium, sodium, potassium, ammonium and tetraalkylammonium ions.

Cyclic ketene acetals A are selected from 2-methylene-1,3-dioxepane (MDO) (I), 4,5-dialkyl-2-methylene-1,3-dioxolane (VI), 5,6-benzo-2-methylene -1, 3 dioxepane (BMDO) (II), 5,6-dialkyl-2-methylene-1,3-dioxepane (IV), 2-methylene-1,3-dioxane (III) and 2-methylene-1,3-dioxolane ( V).

2-methylene-1,3-dioxane

2-M ethylene-1, 3-dioxepane (IM) (MDO)

5,6-Benzo-2-methylene-1,3-dioxepane

(I) (BMDO)

(I ")

2-methylene-1,3-dioxolane

4,5-dialkyl-2-methylene

5,6-dialkyl-2-methylene-1,3-dioxolane 1,3-dioxepane (V)

(VI)

(IV)

In the case of 5, -6-dialkyl-2-methylene-1, 3-dioxepan (IV) and 4,5-dialkyl-2-methylene-1, 3-dioxolane (VI) R ¹ and R ^{2 are} independently a linear or branched alkyl group having 1 to 12 carbon atoms. The linear or branched alkyl group having 1 to 12 carbon atoms is selected, for example, from methyl, ethyl, n-propyl, isopropyl, 1-butyl, 2-butyl, tert-butyl, 1-pentyl, 1-hexyl, 1-heptyl , 1-octyl, 1-nonyl, 1-decyl, 1-undecyl, 1-dodecyl. The proportion of the cyclic ketene acetal A in the hydrolytically degradable polyionic copolymer according to the invention is at least 10 mol%. In this case, 2-methylene-1, 3-dioxepane (MDO) and 5,6-benzo-2-methylene-1, 3-dioxepane are preferred.

The hydrolytically degradable polyionic copolymers according to the invention contain from 4 to 90 mol% of a methacrylic acid derivative B.

Methacrylic acid derivatives B are selected from 2-methylmethacrylate (VII), 2- (2-methyl-1-methylene-allyloxy) -ethanesulphonic acid (VIII) and [2- (2-methyl-1-methylene-allyloxy) ethyl] -phosphonic acid ( IX), if the biodegradable copolymers according to the invention are anionic copolymers:

(VIII)

(IX)

M ^{+ is} a tetraalkylammonium, ammonium, lithium, sodium or potassium cation.

In the case where M ^{+ is} a tetraalkylammonium cation, the four alkyl groups independently of one another are linear or branched alkyl groups having 1 to 12 carbon atoms. The linear or branched alkyl group having 1 to 12 carbon atoms is selected, for example, from methyl, ethyl, n-propyl, isopropyl, 1-butyl, 2-butyl, tert-butyl, 1-pentyl, 1-hexyl, 1-heptyl, 1 Octyl, 1 -nonyl, 1-decyl, 1-undecyl, 1-dodecyl. If the hydrolytically degradable copolymer according to the invention is a cationic copolymerate, the methacrylic acid derivative B is a derivative of N, N-dimethylaminoethyl methacrylic acid (DMAEMA) of the formula (Xa)

wherein 45% to 95% of DMAEMA ionizes in the form of a quaternary amine of formula (Xb),

in which

where n = 0-12 and X ^"is fluoride, chloride or bromide, bromides being preferred over fluorides and chlorides The linear or branched alkyl group having 1 to 12 carbon atoms is selected from, for example, methyl, ethyl, n-propyl, isopropyl , 1-butyl, 2-butyl, tert -butyl, 1-pentyl, 1 -hexyl, 1 -heptyl, 1-octyl, 1 -nonyl, 1-decyl, 1-undecyl, 1 -dodecyl.

Preference is given to those quaternary amines according to formula XI in which R ^{3 is} selected from ethyl, n-butyl, n-hexyl, n-octyl, n-dodecyl.

The hydrolytically degradable polyionic copolymers according to the invention contain 0 to 80 mol% of a methacrylic acid derivative C.

The methacrylic acid derivative C is selected from compounds of the formula

(XII)

in which R ^{4 is} selected from -OCH ₃ , -N (CH ₃ ) ₂ , an oligoethylene glycol of the general formula -O- (CH ₂ -CH ₂ -O) _m H and a co-methoxy-oligoethylene glycol of the general formula -O- (CH ₂ -CH ₂ -O) _m -CH ₃ , where m represents a natural number between 1 and 12.

The methacrylic acid derivative C is preferably selected from oligoethylene glycol methacrylate (to be more specific: nonaethylene glycol methacrylate) OEGMA, 2- (2-methoxyethoxy) ethyl methacrylate (MEO ₂ MA), methyl methacrylate (MMA), N, N, 2-trimethylacrylamide and 2- Methylacrylsäure- (2-hydroxyethyl) ester:

OEGMA

MEOoMA

The hydrolytically degradable copolymers of the invention have a number average molecular weight M _n of 10,000 to 100,000. This applies to both dipolymers and terpolymers.

The ionic copolymers are composed of a) 10 to 55 mol% of a cyclic ketene acetal A selected from MDO and BMDO b) 4 to 90 mol% of a methacrylic acid derivative B, c) 0-80 mol% of a methacrylic acid derivative C, wherein the Sum of components A, B and C is 100 mol%. MDO, BMDO, B and C are as defined above. In a further preferred embodiment, the ionic copolymers are composed of a) 10 to 55 mol% of a cyclic ketene acetal A, b) 4 to 90 mol% of a methacrylic acid derivative B, c) 0-80 mol% of a methacrylic acid derivative C, selected from oligoethylene glycol methacrylate OEGMA, 2- (2-methoxyethoxy) ethyl methacrylate (MEO ₂ MA), methyl methacrylate (MMA), N, N, 2-thmethylacrylamide and 2-methylacrylic acid (2-hydroxyethyl) ester wherein the sum of components A, B and C is 100 mol%. Here, A, B, OEGMA, MEO ₂ MA and MMA are as defined above.

In a further preferred embodiment, the ionic copolymers are composed of a) 10-55 mol% of a cyclic ketene acetal A, b) 4-90 mol% of the methacrylic acid derivative DMAEMA, in which 45% to 95% ionized in the form of a quaternary amine C) 0-80 mol% of a methacrylic acid derivative C, wherein the sum of the components A, B and C is 100 mol%. A, DMAEMA and C are as defined above.

In a further preferred embodiment, the ionic copolymers are composed of a) 10-55 mol% of a cyclic ketene acetal A, b) 4-90 mol% of 2-methyl methacrylate of the formula (VII), c) 0-80 Mol% of a methacrylic acid derivative C, wherein the sum of the components A, B and C is 100 mol%. Here, A and C are as defined above.

In a further preferred embodiment, the ionic copolymers are composed of a) 10-55 mol% of a cyclic ketene acetal A, b) 4-90 mol% of [2- (2-methyl-1-methylene-allyloxy) -ethyl] -ethanesulfonate according to formula (VIII), c) 0-80 mol% of a methacrylic acid derivative C, where the sum of the components A, B and C is 100 mol%. Here, A and C are as defined above.

In a further preferred embodiment, the ionic copolymers are composed of a) 10-55 mol% of a cyclic ketene acetal A, b) 4-90 mol% of [2- (2-methyl-1-methylene-allyloxy) ethyl] c) 0-80 mol% of a methacrylic acid derivative C, wherein the sum of the components A, B and C is 100 mol%. Here, A and C are as defined above.

In a further preferred embodiment, the ionic copolymers are composed of a) 10 to 55 mol% of a cyclic ketene acetal A, b) 4 to 90 mol% of a methacrylic acid derivative B, c) 0 mol% of a methacrylic acid derivative C, wherein the Sum of the components A and B is 100 mol%, so that it is a dipolymer. A, B and C are as defined above.

In a further preferred embodiment, the ionic copolymers are composed of a) from 10 to 55 mol% of a cyclic ketene acetal A selected from MDO and BMDO, b) from 4 to 90 mol% DMAEMA, which contains from 45% to 95% in the form of a quaternary amine c) 0 to 80 mol% of a methacrylic acid derivative C, wherein the sum of the components A, B and C is 100 mol%, and wherein the quaternary amine of the DMAEMA and the methacrylic acid derivative C are as defined above.

In a particularly preferred embodiment, the ionic copolymers are composed of a) 10 to 55 mol% of a cyclic ketene acetal A, selected from MDO and BMDO, b) 4 to 90 mol% DMAEMA, which is 45% to 95% in The form of a quaternary amine is c) 0 to 80 mol% MMA, the sum of components A, B and C being 100 mol% and the quaternary amine of DMAEMA being as defined above.

All ionic copolymers of the invention - both cationic and anionic - are hydrolytically degradable as defined above.

Furthermore, such ionic copolymers of the present invention containing at least 40 mole% ester moieties in the polymer backbone have been evaluated for biodegradability. In the case of cationic copolymers of the invention, the copolymers also contained a maximum of 20% cationic groups, i. not more than 20 mol% of the cationic copolymer was accounted for by quaternary amines from DMAEMA. It has been found that these abovementioned ionic copolymers according to the invention are biodegradable, for example by admixing them with conventional comopters.

By biodegradable it is meant that a compound (here: a copolymer according to the invention is decomposed by enzymes and / or microorganisms into smaller degradation products, preferably those enzymes and microorganisms which can be found in composts. In addition, the antimicrobial activity of the cationic copolymers according to the invention was investigated. It has been found that the cationic copolymers according to the invention are antimicrobial if they contain at least 50 mol% of component B, ie a quaternary amine of DMAEMA according to the above definition of component B. These are, for example, components B according to formula (XIII):

where q is the chain length of component B, and r is a natural number between 1 and 1.

The antimicrobial effect has been demonstrated for both dipolymers and terpolymers on Eschericia coli.

Antimicrobial is understood to mean that a substance (in this case a cationic copolymer according to the invention) reduces the ability to multiply or infect microorganisms or kills or inactivates them.

In summary, for cationic copolymers, it should be noted that a) cationic copolymers containing at least 40 mol% A and at the same time a maximum of 20 mol% B are biodegradable,

b) cationic copolymers containing at least 50 mole% B are antimicrobial, regardless of how many mole% of component A they contain. This applies to both cationic dipolymers and cationic terpolymers. The novel anionic copolymers are prepared by polymerizing components A, B and C in the presence of a free-radical initiator under a protective gas atmosphere and subsequently purifying the resulting ionic copolymer. Component B is selected from a methacrylate (I), a sulfonate (II) and a phosphonate (III) as defined above.

The cationic copolymers of the invention are prepared by a process comprising the following steps: a) free radical copolymerization of components A, DMAEMA and C in the presence of a radical initiator under a protective gas atmosphere, b) purification of the resulting neutral copolymer, c) reaction of the neutral copolymer with a quaternization reaction genz, so that 45 to 95% of the DMAEMA are quaternized, d) purification of the ionic copolymer thus obtained. Component B is DMAEMA (Xa).

The copolymer obtained in this way is neutral because non-quaternized DMAEMA is used. The reaction of the neutral copolymer to the ionic copolymer according to step c) is carried out by reaction with a quaternizing reagent selected from

a primary haloalkane of 1 to 12 carbon atoms, which carbon chain may be linear or branched, and

a benzyl halide of the general formula

where t = 0 to 12, where X is a halogen atom and the halogen is selected from fluoro, chloro and bromo in both the case of the primary haloalkane and in the case of the benzyl halide. Bromalkanes and benzyl bromides are preferred. For this purpose, the neutral copolymer obtained after carrying out step b) is dissolved in an aprotic solvent and then reacted with a haloalkane or benzyl halide as defined above. If the boiling point of the quaternizing reagent is above 60 ° C., the quaternization reaction advantageously takes place at temperatures between 40 ° C. and 45 ° C. However, if the boiling point of the quaternizing reagent below 60 ° C, the quaternization reaction is carried out at room temperature. The degree of quaternization can be controlled by the reaction time. For a given combination of neutral copolymer and quaternizing agent, lengthening the reaction time leads to a higher degree of quaternization. For a given combination of neutral copolymer and reaction time, the use of shorter chain quaternization reagents results in higher quaternization levels. One skilled in the art, by means of his expertise and without departing from the scope of the claims, may determine by routine experimentation which combination of neutral copolymer, quaternizing reagent and reaction time will result in which degree of quaternization.

Alternatively, cationic copolymers of the present invention can be prepared by first quaternizing DMAEMA and then radically polymerizing the quaternized DMAEMA with components A and C in the presence of a radical initiator under a protective gas atmosphere.

The free radical Copolymehsation of components A, B and C is carried out in all the above cases by A, B and C are presented together with a free radical initiator in a reaction vessel under a protective gas atmosphere. Any oxygen present is removed by one-time freezing and thawing of this reaction mixture. Suitable radical initiators are, for example, azobisisobutyronitrile (AIBN), dibenzoyl peroxide (DBPO) and di-tert-butyl-hyponitrite (DTBHN). Other free-radical initiators are known to the person skilled in the art and can be used without departing from the scope of the patent claims. Suitable shielding gases are, for example, argon, nitrogen, carbon dioxide and mixtures thereof.

The free-radical copolymerization is preferably carried out at temperatures between 70 ° C. and 120 ° C. The preferred temperature depends on the initiator. Thus, when AIBN is used, a temperature of about 70 ° C. is preferred, while polymerization is preferably carried out at about 120 ° C. when using di-tert-peroxides. The person skilled in the art knows which temperature ranges should be chosen for which initiator.

The neutral or ionic copolymer is purified by dissolving it in a first organic solvent and reprecipitating it by adding a second solvent. For dissolving the neutral copolymer, for example, chloroform and DMF are suitable. If a short-chain alkyl bromide BrC _p H _{2p +} i, p ≦ 4, is chosen for the quaternization, the solvent used is preferably a mixture of chloroform and an alcohol, for example methanol. The neutral copolymers dissolve well in chloroform, but the ionic copolymers formed during quaternization no longer readily dissolve in pure chloroform, so that the solution becomes cloudy with increasing quaternization of the copolymer. In this case you should add an alcohol, eg methanol, until the solution is clear again.

For dropping the ionic copolymer, an alkane, for example, n-pentane or n-hexane is suitable.

The ketene acetal (component A) is reacted to about 40-60%, so that the amount of ketene acetal used is about twice as high as the proportion of ketene acetal in the product.

If the proportion of ketene acetal (component A) in the educt mixture is up to 50 mol%, the polymerization reaction is complete after 5 hours. This applies to the entire temperature range of the process according to the invention, ie between 70 ° C and 120 ° C, regardless of whether a dipolymer or a terpolymer is prepared (see Embodiments 4 and 6). However, if the proportion of ketene acetal in the educt mixture is more than 50 mol%, the polymerization preferably takes place at a temperature of 120.degree. There- it is advantageous to extend the reaction time to about 12-16 hours. It is known to the person skilled in the art that an increase in the reaction temperature and / or an extension of the reaction time increase the yield of a reaction.

The ionic copolymers according to the invention contain 30-70 mol% of ester units.

In the case of cationic copolymers according to the invention, the water solubility can be controlled and targeted by controlling the proportion of the ester units and the length of the alkyl groups. In this way, a wide variety of cationic copolymers can be prepared from very hydrophobic to very hydrophilic.

The ionic copolymers of the invention have a random structure, i. the monomer units of the individual components A, B and optionally C are randomly distributed in the copolymer. Alternatively, ionic copolymers with block structure can also be prepared. In such block copolymers, the monomers alternate in blocks, i. a section of polymer of a pure monomer component A alternates with a section of a pure monomer component B or C.

The ionic copolymers according to the invention can be used as hydrolytically degradable ionomers. According to IUPAC, ionomer is understood to mean a macromolecule in which a small but nevertheless significant proportion of the constitutional units have ionizable or ionic groups. A constitutional unit is an atom or group of atoms (optionally with other atoms or groups attached thereto) which contains part of the essential structure of a macromolecule, an oligomer, a block or a chain. The ionic copolymers according to the invention are suitable for numerous biomedical and material science applications.

Ionic copolymers of the present invention are particularly advantageous because each of the components contained in them imparts particular properties to the polymer: The cyclic ketene acetals provide ester bonds in the backbone of the polymer which are the cause of hydrolytic degradability. The cationic or anionic moieties provide binding sites for other molecules, such as biomolecules. In the case of ionic terpolymers according to the invention, the water solubility can be adjusted in a targeted manner with the aid of the methacrylic acid derivatives C, for example with the aid of methoxy-oligo- (ethylene glycol) -methacrylates. Methoxy-oligo- (ethylene glycol) methacrylates may also serve to camouflage the terpolymers of the invention in biomedical applications to the immune system. With the aid of methacrylates, the glass transition temperature of the ionic copolymers according to the invention can furthermore be adjusted in a targeted manner. Likewise, by means of methacrylates, the thermoresponsive properties can be deliberately changed, so that copolymers containing methacrylate according to the invention are suitable as injectable biodegradable polyions for biomedical applications, e.g. for the drug release.

Both anionic and cationic copolymers are suitable for the production of nanoparticles. Such nanoparticles have, for example, a higher efficiency in the encapsulation of pharmaceutical active ingredients and, in the field of materials science, a higher stability to shear forces than previous materials.

Cationic copolymers are suitable, for example, as superhydrophobic materials and antibacterial transparent coatings, for example for wood. Of particular note, however, is the suitability of the cationic copolymers as adhesives. It has been shown that, for example, they create a durable, water- and temperature-stable adhesive bond between wood and metal, glass or another piece of wood, and metal and glass bond together just as well. The adhesive properties occur with cationic dipolymers and terpolymers containing at least 4 mole percent quaternized DMAEMA based on the total polymer.

Anionic copolymers are suitable, for example, as biodegradable thermoplastic elastomers, biodegradable ionomers, vehicles for drug delivery, as transfection agents, and as carriers for aerosol therapy and gene therapy.

embodiments

EMBODIMENT 1 Preparation of Neutral Copolymers of BMDO and DMAEMA

Schematic representation of the copolymerization of BMDO and DMAEMA; where v and w are the chain lengths of BMDO and DMAEMA in the final dipolymer.

First, 5,6-dibenzo-1, 3-dioxepane (BMDO) and N, N-dimethylaminoethyl methacrylate (DMAEMA) were copolymerized by free radical polymerization to prepare the hydrolytically degradable polymethacrylic acid amine precursors. Subsequently, the precursors were quaternized with the aid of alkyl bromide in order to obtain the hydrolytically degradable polycations according to the invention.

All copolymerizations were carried out under an argon atmosphere in predried Schlenk tubes. Azobisisobutyronitrile (AIBN) was used as the initiator for the free radical polymerization. In a typical polymerization reaction two monomers - BMDO (0.571 g 5 mmol) and DMAEMA (0.786 g 5 mmol) were charged with 1 mol% of the initiator (based on the total concentration of the monomers) in a Schlenk tube under an argon atmosphere. Small residues of oxygen were released by freezing and thawing once Tube removed. The reaction was started by immersing the reaction tube in a preheated oil bath at 70 ° C. After a reaction time of 5 hours, the reaction mixture was diluted with CHCl ₃ and precipitated with about 200 ml of n-hexane. The copolymers were purified by dissolution in CHCl ₃ and reprecipitation from n-hexane. The copolymers were dried in vacuo at 40 ° C to constant mass. The microstructure of the copolymers was characterized by 1D and 2D NMR. By varying the molar ratio of the two monomers BMDO and DMAEMA in the educt mixture, various copolymers were prepared. The reaction was carried out under the reaction conditions described above.

Table 1 shows the results of the free radical copolymerization of 5,6-dibenzo-2-methylene-1,3-dioxepane (BMDO) and N, N-dimethylaminoethyl methacrylate B = BMDO; D = DMAEMA

Embodiment 2:

Quaternization of the neutral copolymers of BMDO and DMAEMA

Finally, the neutral copolymers were quaternized:

Schematic representation of the quaternization of the dipolymer from BMDO and DMAEMA; where v and w are the chain lengths of BMDO and DMAEMA in the final dipolymer.

A representative example is given below: 500 mg of the neutral copolymer were dissolved at 25 ° C. in 50 ml of chloroform. Then, 15 ml of 1-bromododecane (BrCl ₂ H ₂ S) was added. The quaternization reaction was carried out for 3 days by stirring and heating to 40 ° C. in an oil bath. Thereafter, the solvent was removed. The reaction product was purified by dissolving the obtained ionic copolymer twice in chloroform and dropping from n-hexane. The degree of quaternization was determined by elemental analysis, comparing the amounts of bromine and nitrogen.

Various cationic copolymers were prepared by changing the molar ratio of the three starting components (BMDO, DMAEMA and 1-bromododecane.

Table 2 shows the quaternization with Ci ₂ H _2S Br and the physical properties of the quaternized copolymers of BMDO (B) and DMAEMA (D).

Embodiment 3

Quaternization of neutral copolymers of BMDO (B) and DMAEMA

(D) with different 1-bromo-n-alkanes

a) Quaternization with BrC _p H _{2p +} i (p> 4)

500 mg of the poly (BMDO-DMAEMA co-ester) was dissolved in 50 ml of chloroform at room temperature. Then, about 60 mmol of the alkyl bromide was added to the reaction mixture, that is, for example, 14 ml of 1-bromododecane or 8.5 ml of 1-bromohexane). The quaternization reaction was carried out for 3 days by stirring and heating to 40 ° C in an oil bath. Subsequently, the crude product was isolated by distilling off the solvent on a rotary evaporator. The purification of the obtained ionic copolymer was carried out by dissolving it twice in chloroform and reprecipitating from n-hexane.

b) Quaternization with BrC _p H _{2p +} i (2 <p <4)

500 mg of the poly (BMDO-DMAEMA co-ester) was dissolved at room temperature in 40 ml of chloroform. Then, about 60 mmol of the alkyl bromide, ie, 4.5 ml of bromoethane, was added to the reaction mixture. The quaternization reaction was carried out at room temperature. As soon as the solution started to become cloudy, so much methanol was added until it became clear again. After 3 days reaction time, the crude product was first isolated by distilling off the solvent on a rotary evaporator. The cleaning of the obtained ionic copolymer was carried out by twice dissolving in chloroform / methanol and reprecipitation from n-hexane.

Table 3 shows reaction times and degrees of quaternization when using different bromoalkanes and at different quaternization times. "Conversion" refers to the percentage of DMAEMA units in the polymer that were quaternized.

Embodiment 4

Use of the quaternized copolymers of BMDO and DMAEMA as

coatings

The cationic copolymers obtained from Example 2 were applied to glass by electrospinning / electrospray or filmcoating as a coating. In this case, a solution of 10 to 20 wt .-% of the respective inventive cationic copolymer was used in DMF.

a) coating of glass with an ionic polymer by film coating

Copolymers of the invention having a degree of quaternization of at least 4%, which had been quaternized by means of BrCpH 2p + 1 (p> 8), were dissolved in CHCl ₃ to a 10% solution. Each 100 μl of such a solution was poured onto a glass slide for microscopy (7.5 cm x 2.5 cm). After complete drying of the coating, the contact angle was determined to be about 90 degrees.

b) Coating of glass with an ionic polymer by electrospinning

Various 10 to 20% solutions of cationic copolymers were prepared in a suitable solvent such as CHCl ₃ and then electrospun. The voltage was about 55 kV in electrospinning, the distance between capillary and substrate electrode 12 cm and the supply of polymer solution 1 ml / h. The electrospinning was carried out at 20 ° C. The obtained fibers were collected on aluminum foils. The contact angle of the fibers was determined to be about 120 degrees. Embodiment 5:

Preparation of neutral terpolymers of BMDO, DMAEMA and MMA

Cycloketene acetals, such as 5,6-benzo-2-methylene-1,3-dioxepane (BMDO), N, N-dimethylaminoethyl methacrylate (DMAEMA) and a third comonomer, such as methyl methacrylate (MMA), became the hydrolytically degradable neutral copolymer by free radical polymerization terpolymerized. In general, all terpolymerization reactions were carried out under an argon atmosphere in predried Schlenk flasks. As a radical starter AIBN was used.

In a typical polymerization reaction, three monomers, BMDO (1135g 7mmol), MMA (0.250g 2.5mmol) and DMAEMA (0.079g 0.5mmol) in a ratio of 70: 25: 5 together with one mole% AIBN, based on the Total amount of monomers, submitted under argon atmosphere in a Schlenk tube. Small residues of oxygen were removed from the tube by one-time freezing and thawing. The reaction was started by immersing the reaction tube in a preheated oil bath at 70 ° C. After a reaction time of 20 hours, the reaction mixture was diluted with CHCl ₃ and precipitated with about 200 ml of n-hexane. The copolymers were purified by dissolution in CHCl 3 and reprecipitation from n-hexane. The copolymers were dried in vacuo at 40 ° C to constant mass. The microstructure of the copolymers was characterized by 1 D and 2 D NMR. By varying the molar ratio of the comonomers in the educt mixture, various terpolymers of BMDO, MMA and DMAEMA were prepared.

The reaction conditions were chosen essentially as described above.

Table 4 shows the educt mixtures used in this embodiment, the yield, the composition of the resulting terpolymers and their respective Quaternisierungsgrad.

Embodiment 6:

Quaternization of terpolymers of BMDO, DMAEMA and MMA

The neutral precursor terpolymers of Example 4 were quaternized with alkyl bromide. This gave rise to the hydrolytically degradable cationic copolymers according to the invention.

500 mg of the respective terpolymer of Example 4 were dissolved at room temperature in 50 ml of chloroform. Then 15 ml of 1-bromododecane (BrCl ₂ H ₂ S) was added to this solution. The quaternization reaction was carried out for 3 days with stirring and heating to 40 ° C in an oil bath. The quaternized terpolymer was purified by dissolving the cationic terpolymer twice in chloroform and repopulating from n-hexane. The degree of quaternization was determined by elemental analysis comparing the amounts of bromine and nitrogen.

Embodiment 7:

Preparation of neutral terpolymers of MDO, DMAEMA and MMA

Various neutral precursor terpolymers of MDO, DMAEMA and MAA were prepared as described for the corresponding terpolymer from BMDO / DMAEMA / MAA. Table 5 shows the results of free radical terpolymerization of MDO, DMAEMA and MMA.

Embodiment 8:

Quaternization of terpolymers of MDO, DMAEMA and MMA

Several neutral precursor terpolymers of MDO, DMAEMA and MMA were prepared and then quaternized with 1-bromododecane, all terpolymers for ionomers containing the same amount of MDO (40 mole%, see Table 4). Polymerization and quaternization were carried out as described for the corresponding terpolymer from BMDO / DMAEMA / MAA. Table 6 shows the results of quaternization.

Embodiment 9: Adhesive Properties of the Cationic Copolymers

Various cationic copolymers of the invention were prepared. As dioxepan, BMDO or MDO was used. BMDO or MDO were free-radically polymethylated with DMAEMA and optionally with MMA. The precursor copolymers (dipolymers or terpolymers) obtained in this way were quaternized with 1-bromoalkanes. The cationic copolymers thus obtained contained at least 4 mol% of cationic groups, ie, at least 4 mol% of the cationic copolymer was accounted for by quaternary amines of DMAEMA. Subsequently, solutions of each of a cationic copolymer according to the invention were prepared in chloroform (10 wt .-% copolymer). These solutions have been successfully used to glue wood to wood, metal or glass and glass to metal. The bond strength remained unchanged even after 24 hours of treatment of the parts thus joined in 60 ° C hot water.

Embodiment 10:

Biodegradability of the cationic copolymers

Cationic copolymers containing at least 40% backbone ester moieties and not more than 20 mole% cationic groups were processed into films. Films of these copolymers (10 cm x 2 cm x 0.1 mm) were buried in the compost. After two weeks, clear holes were visible in the films. This showed that cationic copolymers were already degraded by enzymes and microorganisms within this short time, whereby the composting rate is known to depend on the soil moisture, the temperature and also the type of soil.

Claims

claims

1. Hydrolytically degradable polyionic copolymers which are composed of d) 10 to 55 mol% of a cyclic ketene acetal A, e) 4 to 90 mol% of a methacrylic acid derivative B, f) 0 to 80% mol% of a methacrylic acid derivative C, wherein the sum of the components A, B and C is 100 mol%, and wherein

the cyclic ketene acetal A is selected from

2-methylene-1,3-dioxane

2-M ethylene-1, 3-dioxepane (IM) (MDO)

5,6-Benzo-2-methylene-1,3-dioxepane

(I) (BMDO)

(I ")

2-methylene-1,3-dioxolane

4,5-dialkyl-2-methylene

5,6-dialkyl-2-methylene-1,3-dioxolane 1,3-dioxepane (V)

(VI)

(IV) in which R ¹ and R ² independently of one another represent a linear or branched alkyl group having 1 to 12 carbon atoms, and the methacrylic acid derivative B is selected from

2-methyl-methacrylate (VII)

M

[2- (2-methyl-1-methylene-allyloxy)] ethanesulfonate (VIII)

[2- (2-Methyl-1-methylene-allyloxy) ethyl] -phosphonate (IX)

N, N-Dimethylaminoethylmethacrylic acid (DMAEMA) according to formula (Xa)

wherein 45% to 95% of DMAEMA is ionized in the form of a quaternary amine of formula (Xb), so that it is a cationic in polyionic copolymer

Copolymehsat acts, wherein

with n = 0-12 and X ^"is fluoride, chloride or bromide,

and wherein the methacrylic acid derivative C is selected from compounds according to formula (VI)

wherein R is selected from

-OCH ₃ , -N (CH ₃ ) 2, an oligoethylene glycol of the general formula -O- (CH ₂ -CH ₂ -O) m H, a co-methoxy-oligoethylenglykol of the general formula -O- (CH ₂ -CH ₂ - O) _m -CH ₃ , where m is a natural number between 1 and 12, Vinyl acetate, acrylonitrile, 2-hydroxyethyl methacrylate, N-vinylformamide, N-vinylacetamide, N-methyl-N-vinylacetamide, N-vinylcaprolactam, N-vinylpyrrolidone, N-2-hydroxypropylmethacrylamide, N-3-hydroxypropylmethacrylamide, N, N Dimethylacrylamide, styrene, N, N-dimethylaminostyrene.

2. Hydrolytically degradable ionic copolymers according to claim 1, characterized in that the cyclic ketene acetal A is selected from 5,6-benzo-2-methylene-1, 3-dioxepan (BMDO) and 2-methylene-1, 3-dioxepan ( MDO).

3. Hydrolytically degradable ionic copolymers according to one of claims 1 and 2, characterized in that the methacrylic acid derivative C is selected from

OEGMA

MEOoMA

4. Hydrolytically degradable ionic copolymers according to one of claims 1 to 3, characterized in that the methacrylic acid derivative B is N, N-dimethylaminomethylmethacrylic acid, in which 45% to 95% of the DMAEMA ionized in the form of a quaternary amine of the formula (X b) are available

in which

where n = 0-12 and X ^"is fluoride, chloride or bromide.

5. Hydrolytically degradable ionic copolymers according to one of claims 1 to 3, characterized in that the methacrylic acid derivative B is 2-methyl methacrylate of the formula (VII)

where M ^{+ represents} a lithium, sodium, potassium, ammonium or tetraalkylammonium cation.

6. Hydrolytically degradable ionic copolymers according to one of claims 1 to 3, characterized in that it is in the derivative B of the methacrylic [02- (2-methyl-1-methylene-allyloxy) ethyl] -ethansulfonat according to formula (VIII )

7. Hydrolytically degradable ionic copolymers according to one of claims 1 to 3, characterized in that it is in the methacrylic acid derivative B to [2- (2-methyl-1-methylene-allyloxy) ethyl] phosphonate according to formula (IX )

8. Hydrolytically degradable ionic copolymers according to one of claims 1 to 7, characterized in that they are composed of a) 10 to 55 mol% of a cyclic ketene acetal A, b) 4 to 90 mol% of a methacrylic acid derivative B, c) 0 Mole% of a methacrylic acid derivative C, wherein the sum of components A and B is 100 mole%, so that it is a dipolymer, and wherein A, B and C are as defined above.

9. Hydrolytically degradable ionic copolymers according to one of claims 1 to 6, characterized in that they are composed of a) 10 to 55 mol% of a cyclic ketene acetal A, selected from MDO and BMDO, b) 4 to 90 mol% DMAEMA c) from 0 to 30 mol% of a methacrylic acid derivative C, the sum of components A, B and C being 100 mol%, and wherein the quaternary amine of DMAEMA is from 45 to 95% in the form of a quaternary amine and the methacrylic acid derivative C are as defined above.

10. Hydrolytically degradable ionic copolymers according to one of claims 1 to 6, characterized in that they are composed of a) 10 to 55 mol% of a cyclic ketene acetal A, selected from MDO and BMDO, b) 4 to 90 mol% DMAEMA which is 45% to 95% quaternary amine; c) 0 to 80 mole% MMA, wherein the sum of components A, B and C is 100 mole%, and wherein the quaternary amine of DMAEMA is as above is defined.

11. A process for the preparation of cationic copolymers according to claim 4, comprising the following steps: a) free radical copolymerization of components A, DMAEMA and C in the presence of a radical initiator under a protective gas atmosphere, b) purification of the resulting neutral copolymer, c) reaction of the neutral copolymer with a quaternization reagent so that 45% to 95% of the DMAEMA are quaternized; d) purification of the ionic copolymer thus obtained.

12. A process for the preparation of cationic copolymers according to claim 11, characterized qekennzeichent that first DMAEMA is quaternized according to step c) and the quaternized DMAEMA then in step a) with the components A and C in the presence of a radical initiator under a protective gas atmosphere free-radical polymehsiert.

13. A process for preparing anionic copolymers according to any one of claims 5 to 7, characterized in that the components A, B and C polymehsiert in the presence of a radical initiator under a protective gas atmosphere and the resulting ionic copolymer is subsequently purified.

14. Use of hydrolytically degradable ionic copolymers according to any one of claims 1 to 10 for the preparation of nanoparticles.

15. Use of hydrolytically degradable cationic copolymers according to any one of claims 1 to 4 and 8 to 10 as adhesives.

16. Use of hydrolytically degradable cationic copolymers according to any one of claims 1 to 4 and 8 to 10 as superhydrophobic materials.

17. The use of hydrolytically degradable anionic copolymers according to any one of claims 1 to 3 and 5 to 8 as biodegradable thermoplastic elastomers or biodegradable ionomers.