MX2008003605A - Novel quaternary polymers - Google Patents

Abstract

The present invention relates to novel quaternized polymers, especially of chitin/chitosan type, and to carbohydrate polymers carrying quaternized ammonium groups, especially piperazinium groups. Such polymers are characterized i.a. by improved solubility characteristics.

Description

NEW QUATERNARY POLYMERS FIELD OF THE INVENTION This invention is directed to new quaternary polymers and methods for adding portions of quaternary ammonium in oligomers or polymers, such as any natural, semi-synthetic or synthetic polymer, preferably to chitosan and chitin, via different spacers covalently attached. These quaternary ammonium polymer derivatives have improved aqueous solubility, usability and activity in many industrial applications, for example, in pharmaceutical applications, in cosmetics, food science, water purification, pulp and paper industry, and in the textile industry. One or more quaternary portions can be inserted into a monomer unit of the polymer. This unit is also directed to the piperazinium mono- and di-quaternary acids usable in the preparation of the polymers, as well as to the methods of their preparation.

ENVIRONMENT OF THE INVENTION Chitosan (poly-1, 4-ß-D-glucosamine) is a non-toxic polysaccharide (Journal of Biomedical Material Research 59, 2002, 585) and biodegradable (Biomaterials 20, 1999, 175) which is derived from chitin by means of deacetylation under basic conditions. The term chitosan is used to describe a wide variety of glucosamine and N-acetylglucosamine heteropolymers with varying degrees of deacetylation and molecular weights. Chitosan has many potential applications in various fields, for example, in pharmacy and medicine (Drug Development and Industrial Pharmacy 24, 1998, 979; Pharmaceutical Research 15, 1998, 1326; STP Pharma Science 10, 2000, 5), food science (International Dairy Journal 14, 2004, 273, Agro Food Industry Hi-Tech 14, 2003, 39), water purification (Water Research 34, 2000, 1503), pulp and paper industry (Journal of Applied Polymer Science 91, 2004 , 2642), and in the Textile Industry (Journal of Macromolecular Science Polymer Revie s C43, 2003, 223).

The main obstacle to the use of chitosan in different applications are its poor solubility properties, especially the poor aqueous solubility. The poor solubility of chitin and chitosan is due to the strong intra- and intermolecular binding of hydrogen leading to highly crystallized structures. The chitosan it only dissolves in aqueous acid solutions due to the protonation of the amino groups in the polymer. Chitosan is poorly soluble in all common organic solvents. Chitosan becomes soluble in water when the degree of deacetylation is approximately 50% due to the unfavorable conformation to form intermolecular hydrogen bonds (Biomacromoilecules 1, 2000, 609). Several derivatives of chitin and chitosan have been designed and synthesized, mainly to improve the solubility properties of chitosan (Progress in Polymer Science 26, 2001, 1921, Progress in Polymer Science 29, 2004, 887). The soluble anionic derivatives of chitosan are carboxyl acid derivatives (International Journal of Biological Macromolecules 14, 1992, 122, European Polymer Journal 39, 2003, 1629), phosphates (Carbohydrate Polymers 44, 2001, 1) and sulfates (Carbohydrate Research 302, 1997, 7). Other water-soluble chitosan derivatives are poly (ethylene glycol) derivatives (Carbohydrate Polymers 36, 1998, 49).

The important water-soluble chitosan derivatives are derivatives with a quaternary ammonium moiety. These derivatives have two main advantages over the parent chitosan: (1) they are soluble in water on a wide pH scale including neutral and basic conditions, and (2) have a permanent positive charge on the polymer's main element. The polycationic nature is commonly seen as responsible for the unique properties and activity of chitosan. The quaternary chitosan derivatives can be prepared either by quaternizing the amino group already present in the polymer or by adding one or a few quaternary ammonium portions. The synthesis of (N, N, N) -trimetilquitosano has been widely studied and reported (Carbohydrate Polymers 5, 1985, 297; International Journal of Biological Macromolecules 8, 1986, 105; Carbohydrate Polymers 24, 1994, 209; Carbohydrate Polymers 36, 1998, 157; Drug Development and Industrial Pharmacy 27, 2001, 373). The pharmaceutical properties of (N, N, N-trimethylquintose have been widely studied (EG, European Journal of Pharmaceutics and Biopharmaceutics 58, 2004, 225, Biomaterials 23, 2002, 153, Carbohydrate Research 333, 2001, 1). even well-defined structures derived from 1-chitosan can not be obtained by direct methylation if the hydroxyl groups are not protected The hydroxyl groups in the polymer, ie the primary hydroxyl in the 6-position and the secondary hydroxyl in the 3-position, they are also methylated, high degrees of quaternization can not be obtained without Total O-methylation of the polysaccharide (Carbohydrate Polymers 36, 1998, 157).

The amino group in the chitosan has also been quaternized first reductively, alkylating it with aldehydes to form imines, followed by reduction, to obtain the N-alkyl derivatives. These alkyl derivatives have also been quaternized with alkyl iodides (Polymer Bulletin 38, 1997, 387, Carbohydrate Research 333, 2001, 1, European Polymer Journal 40, 2004, 1355). Uragami and colleagues have cross linked to (N, N,?) -trimethylchitosan with various cross-linking agents, for example, with tetraethoxysilane (Biomacromolecules 5, 2004, 1567) and with diethylene glycoliglycidyl ether (Macromolecular Chemistry and Physics 203, 2002 , 1162). Murata et al. quaternized some of the amino groups in the galactose derivative of chitosan (Carbohydrate Polymers 29, 1996, 69; Carbohydrate Polymers 32, 1997, 105). Ucheqbu et al. Prepared a quaternary ammonium palmitoyl chitosan to obtain a polyhalogen for drug delivery (International Journal of Pharmaceutics 224, 185-199). However, all these share the problem with the (N, N,?) -trimethylchitosan, ie, the uniform structures can not be obtained due to the methylation of the hydroxyl group of the polymer during the process of synthesis.

The quaternary ammonium portion can be inserted into polymer structures via several spacers. N- [(2-hydroxy-3-trimethylammonium) propyl] chitosan chloride can be obtained by reaction of chitosan with glycidyltrimethylammonium chloride (Biomaterials 24, 2003, 5015; Carbohydrate Research 339, 2004, 313; Coloration Technology 120, 2004, 108; Colloids and Surfaces A: Physicochemical Engineering Aspects 242, 2004, 1; Polymer Journal 32, 2000, 334, International Journal of Biological Macromolecules 34, 2004, 121-126). This N- [(2-hydroxy-3-trimethylammonium) -propyl] chitosan has been studied for different applications, such as in cosmetics (for example, US4772690; US4822598; US4976952). This derivative with varying lengths of alkyl chains attached to the quaternary nitrogen, has also been described as an antimicrobial agent (US6306835) and as a cholesterol lowering agent (WO9206136).

Another example of quaternary chitosan derivatives is chitosan N-betainate (Macromolecules 37, 2004, 2784; S.T.P. Pharma Sciences 8, 1998, 291). Lee et al. prepared quaternized diaminoalkyl chitosans to obtain chitosan derivatives that have two portions Quaternary (Bioscience Biotechnology and Biochemistry 63, 1999, 833; Bioorganic &Medicinal Chemistry Letters 12, 2002, 2949). Chun-Ho et al. prepared and studied the antibacterial activity of (triethylaminoethyl) chitin (Polymers for Advanced Technologies 8, 1997, 319). Suzuki et al. prepared methylated N-p (N-methylpyridinium) chitosan and N-4 - [(3-trimethylammonium) propaxy] benzylated chitosan and studied the electrical resistance of these materials (Polymer Journal 32, 2000, 334).

Other polysaccharides have also been modified by inserting a portion of quaternary ammonium, for example, cellulose (Macromolecular Materials And Engineering 286, 2001, 267) and starch (International Journal of Biological Macromolecules 31, 2003, 123). These are some commercial producers of these water-soluble quaternary derivatives of starch and cellulose. Tsai et al. Reported alkylation of the starch with mono-quaternary 4,4-diethyl-1- (chloroethyl) piperacioniochloride chloride and diquaternary 1-glycidyl-1,4-trimethylpiperazinium dichloride (US5349089). However, no physicochemical properties were reported, for example, aqueous solubility of these alkylated starch derivatives.

Previously, we prepared derivatives of non-quaternary N-methylpiperazine chitosan, but these were only relatively more soluble in water than the parent chitosan (Biomacromolecules 6, 2005, 858). By preparing quaternary piperazine derivatives we can obtain derivatives that are highly soluble in water over a wide pH range. Nevertheless, the quaternary piperazine derivatives can not be prepared directly from these non-quaternary chitosan derivatives. To obtain a quaternary nitrogen atom, hard reaction conditions are needed, usually with a large excess of the alkylating reagent. It is impossible to obtain well-defined chitosan derivatives by alkylating the non-quaternary chitosan derivatives, since this approach would result in a heteropolymer with both dicuaternary and monoquaternary portions in the monomers. The hydroxyl groups in the chitosan should also be alkylated. Alkylation of the hydroxyl groups has been shown to decrease the aqueous solubility of chitosan, for example, Sieval et al. reported that quaternary chitosan derivatives with a high degree of O-methylation were insoluble in water, even with a high degree of quaternization (Carbohydrate Polymers 36, 1998, 157). This also proves that quaternary chitosan derivatives, even with high degree of quaternization, are not necessarily soluble in water.

DESCRIPTION OF THE INVENTION According to a first aspect, the present invention is directed to a new group of polymers represented by the following general formula: where: T is NH or O, Xi, X2 and X3 are, independently, H or: in the case that T is NH (ie, chitin and chitosan), Xi, X2 and X3 can also be: and, in addition, Xi can also be: i? -C-CH, where R2 and R3 are independently H or a substituted or unsubstituted, straight or branched alkyl chain having from 1 to 6 carbon atoms, and m is an integer from 1 to 12, Y is a quaternary ammonium portion selected from portions of piperazine having the formula: (A) (B) (C) or selected from among the groups: (FROM) where R4 and R5 are independently a substituted or unsubstituted, linear or branched alkyl chain with 1 to 6 carbon atoms, Z is a negatively charged counterion, preferably selected from the group consisting of of Cl ", Br", I ", OH", R "COO", R "S04", where Ri is H or an alkyl group with 1 to 6 carbon atoms or an aromatic portion, where the degree of substitution ( gs) of the quaternary substituent for the total of the groups Xi, X2 and X3 is at least 0.01, n is the degree of polymerization, and can be an integer from 2 to 100,000, with the proviso that, when T is O, Y it can only have the meaning of a group of the formula (A), (B), (C) or (E) as defined.

The invention is also directed to methods for preparing the new quaternary polymers, as well as the mono and di-quaternary piperazinium acids of the formula: vma vm where R2, R3, R4, R5, m and Z are as defined above, as well as the basic salts thereof, as well as the methods for preparing them.

According to another aspect, the invention is addresses novel derivatives of any carbohydrate polymer, or any other natural, semi-synthetic or synthetic polymer having a hydroxyl group or amino substituted with a quaternary group as defined above for Xi, X2 or X3, where Y is a piperazine mono group or di-quaternized from formula (A), (B), (C) or (E) as defined above.

DETAILED DESCRIPTION OF THE INVENTION The monomer units of the quaternary polymers can be independently substituted by the groups Xi, X2 and X3. Therefore, there may be different monomers in the polymers, that is, one or more of the functional groups in some of the monomer units are substituted with quaternary groups (ie, Xi, X2 and / or X3 = + R |) and some are unsubstituted (ie, Xi, X2 and X3 = H). In the case where T is NH (ie, chitin and chitosan), Xi, X2 and X3 can also be: R. f? -fe? ^ and, in addition, Xi can also be: jí _ These different monomers may be evenly distributed within the polymer structure or may also form block structures. The degree of substitution of the quaternary substituent: or R? GO? in the polymer structure it can be from 0 to 1, independently for each of groups Xi, X and X3, however, the general degree of substitution being for all groups Xlf X2 and X3 being at least 0.01 in order to provide a necessary quaternary substituent content in the polymer. The maximum degree of substitution is 3, in which case there are three quaternary substituents per monomer in each monomer unit of the polymer. A degree of substitution of, for example, 0.01 for a substituent means that there is on average 1 of these substituents per 100 monomer units in the polymer, and a degree of substitution of 1 means that there is on average one substituent in each unit of polymer monomer.

Typically, the degree of substitution for the quaternary group will fall on the scale of 0.05 to 1. No However, the optimal degree of substitution depends on the applications in which these quaternary polymer derivatives are used.

In the formula above, an alkyl group in the meaning of Ri to R5 contains from 1 to 6 carbon atoms, preferably from 1 to 4 carbon atoms, and preferably in a straight chain. An advantageous alkyl group is the methyl group. In the formula above, R2 and R3 are preferably hydrogen. The alkyl group can be unsubstituted or substituted, whereby the substituents can be lower alkoxy (1-3 carbon atoms), hydroxy or halogen.

Within the context of the invention, an aromatic group is advantageously a phenyl group, a benzyl group or a naphthyl group, which may be unsubstituted or substituted with one to three substituents selected from lower alkyl or lower alkoxy (1-3 atoms) carbon) or halogen.

In the formula above, n is the degree of polymerization, and can be an integer than from a polymer with 2-100,000 structural units, ie, the polymer can range from a dimer with two monomers to a polymer with a molecular weight of at least 10,000,000.

A preferred group of polymers are those in which T is NH, Xi, X2 and X3 are as defined above, where Y is one of the groups having the formulas (A), (B) or (C), and where the degree of substitution of the quaternary group is from 0.01 to 1, preferably from 0.05 to 1.

A preferred group of polymer derivatives is formed by those having the formula (I) above, where T is NH, X2 and X3 are hydrogen and Xi is hydrogen, acetyl or a group containing a portion of quaternary ammonium, especially one of the groups having the formulas (A) to (E), and in particular the formulas (A), (B) or (C). In that case, the degree of substitution of the quaternary group will range from 0.01 to 1, preferably from 0.05 to 1.

According to a preferred embodiment, when the main element of the polymer is starch, cellulose, pullulan or dextran, the general formula of the polymer derivative is: where Xi, X2, X3 have the formulas presented above, where Y has the meaning of a quaternary group of the formula (A), (B), (C) or (E), and R2, R3, R4, R5 , Z ", myn are as defined above, and the degree of substitution of the quaternary group in the polymer is 0.01 to 1.

As in the case of chitin and chitosan, there may be different monomer units in the polymers of the formula (II), that is, in any monomer unit one or more of the functional groups may be substituted (ie Xl X2 and / or X3) or the functional groups can be unsubstituted (i.e., Xi, X2 and X3 = H). The different monomer units can be evenly distributed or they can also form block structures within the polymer structure. The degree of substitution of the quaternary groups is as described above for the chitin and chitosan structures.

The present invention is also directed to mono and di-quaternary piperazinium acids of the formulas Villa and VlIIb given below, as well as to the methods for their preparation. This type of portions have been constructed within, for example, prodrug molecules, to improve the aqueous solubility of the parent compound (Pharmaceutical Research 13, 1996, 469). The reported quaternary piperazinium derivatives have been synthesized by first linking the secondary or tertiary portion of piperazine with a meta compound, followed by quaternization with alkyl halides. Unfortunately, this strategy often leads to mixtures of products, especially when the parent molecule has numerous functional groups, which leads to the need for laborious separation of salts and byproducts of mono- and di-quaternary piperazinium.

The new piperazinium mono and dicuaternary acids have the following formulas: VTITIA VTITIb where R2, R3, R4, R5, m and Z "are as defined above, and their salts.

The proper forms of basic salts they comprise, for example, the ammonium salts, the alkali metal and alkaline ferrous salts, for example, salts of lithium, sodium, potassium, magnesium, calcium and the like, salts with organic bases, for example, trimethylamine, triethylamine, triethanolamine, N-methyl-N, N-diethanolamine, ethylenediamine, and salts with amino acids such as, for example, arginine, lysine and the like.

The piperazinium acids are prepared by reacting a compound having the formula: where R2, R3, R4 and m have the meaning given above and E is hydrogen or any protecting group commonly used for the carboxyl portion (Green TW, Wuts PGM: Protection for the Carboxyl Group. Protective Groups in Organic Synthesis, 3rd Edition. Pages 369-453. John Wiley & Sons 1999), preferably ethyl, which can be removed, for example by hydrolysis to form the corresponding acid, with a quaternizing compound corresponding to the group R5, such as an alkyl halide, alkyl fluorosulfonate, dialkyl sulfate, alkyl tosylate, or suitable alkyl mesylate, to form a mixture of the compounds having the formulas: Villa 'vpib * where R2, R3, R4, R5, m and E have the meaning given above, thereafter separating the compounds and, if necessary, converting the thus separated compounds into their corresponding acids, and optionally converting the acid obtained into a salt as defined above. The separation of the two compounds can preferably be carried out by precipitating one of the compounds, preferably the quaternary piperazinium acid (i.e. Villa1) / by means of a suitable choice of the solvent, whereby the other compound will remain in solution.

Suitable solvents for use are, for example, acetonitrile, pyridine, t-butanol, 1-butanol, methyl ethyl ketone, 2-propanol, 1-propanol, acetone, ethanol, methanol, nitrobenzene, dimethylformamide, ethylene glycol, DMSO and water. . The person skilled in the art can for example, based on the dielectric constants of the solvents, select the solvents with ease, in which, for example, the di-quaternized compound will be precipitated, and the mono-quaternized compound will remain in solution, from where it can be recovered, for example, by evaporation.

In the following, when the term chitosan is used, it is meant to mean both chitin and chitosan.

The chitin and chitosan derivatives according to the invention containing a quaternary ammonium group in Xi, X2 and / or X3, can generally be prepared by reacting a chitin derivative or chitosan having a free amino or hydroxyl group, thereby the remaining reactive groups are optionally protected, with a compound having the formula V: where A is an activation group, Y 'is a suitable leaving group or is a Y quaternary ammonium group, m and Y are as defined above, or with a compound having the formula III: where L is a leaving group, and Y 'is any of a Y-group of quaternary ammonium or a leaving group, and R2, R3, m and Y are as defined above, whereby L is a leaving reagent group as good as, or better than, or more reactive, compared to a leaving group Y ', and where an intermediate compound containing a leaving group Y' is obtained, the intermediate is then reacted with a tertiary or aromatic amine corresponding to the Y group of quaternary ammonium , to produce the desired quaternary polymer, and remove any protecting groups.

In formula III, L may be, for example, triflate, tosylate, mesylate, bromide or iodide, and Y ', as a leaving group, may be, for example, chloride.

According to the invention, a compound obtained, in which Xi, X2 and / or X3 have the meaning of hydrogen, can be converted to a compound in which Xi, X2 and / or X3 are different from hydrogen, by reacting the same with a compound of formula III or V, where the symbols have the meaning that was defined, and reacting an intermediate thus obtained containing a leaving group Y1, with a tertiary or aromatic amine corresponding to the Y group of quaternary ammonium, and removing any protective group optionally used in the reaction.

According to the invention, for the preparation of a compound containing a group X2 and / or X3 which is different from hydrogen, and where Xi is different from a group containing a quaternized group, a derivative of chitin or chitosan, where the amino group is protected and one or both of the hydroxyl groups are deprotected, reacted with a compound of formula III or V, where the symbols have the meaning that was defined, and any intermediary obtained in which Y1 is a group reacts salient, with a tertiary or aromatic amine corresponding to the group Y of quaternary ammonium and removing any protective groups.

A chitin or chitosan derivative according to the invention, wherein Xi is a group as defined above containing a quaternary ammonium group, can be prepared for example by reacting a chitin polymer or a chitosan in which the hydroxyl groups in positions 3 and / or 6 are optionally protected, and having a free amino group in one or more of the monomer units of the chitosan polymer, with a compound of formula III or V as defined above, and then in a second step, if necessary, with a tertiary or aromatic amine corresponding to the Y group of quaternary ammonium and removing any protective groups.

According to one embodiment, the polymers in which Xi is a group as defined above containing a quaternary ammonium group and X2 and X3 are hydrogen, can be prepared by reacting a chitin or chitosan polymer in which the hydroxyl groups in positions 3 and / or 6 are optionally protected, and the amino group in one or more of the monomer units of the polymer carries an alkyl or alkyloxy group corresponding to group Xi, where the group Y is replaced by a suitable leaving group, with a tertiary or aromatic amine corresponding to the Y group of quaternary ammonium, and removing any protecting groups.

According to a second embodiment, for the preparation of the polymers having an amino group substituted with a group Xi containing a quaternary amino group, a polymer of chitin or chitosan having a free amino group and in which the hydroxyl groups at positions 3 and / or 6 are optionally protected, is reacted with a compound having the formula III or V as defined above, and when Y 'in formula III or V is a leaving group, the intermediate thus obtained reacting with a tertiary or aromatic amine corresponding to the group Y, and removing any protecting groups.

Examples of these methods are illustrated by method A or method B, which are shown in Schemes I and II, respectively. Scheme I illustrates the reaction for a monomer unit in the starting polymer where the amino group has been substituted with an alkyl or alkyloxy group bearing a leaving group Y1.

Method A Scheme I Therefore, the quaternary ammonium polymers of the formula VII can be prepared by means of a substitution reaction of the polymer with a tertiary or aromatic amine corresponding to the group Y. In the formula, P is independently H or a protecting group. The protecting group can be, for example, a triphenylmethyl group (Tr), a benzyl group, p-nitrobenzyl, p-methoxybenzyl, t-butyl, allyl or acetyl. A particularly preferred protecting group for use in this invention is the triphenylmethyl group (Tr); Y 'is a suitable leaving group, for example, chlorine, tosylate, iodine, etc., preferably bromine or chlorine. R2 and R3 are as defined above, and q is 0 or 1, indicating the absence (q = 0) or the presence (q = 1) of a keto group in the amino substituent.

In a first step (a) the intermediate the protected or deprotected is reacted with any tertiary or aromatic amine corresponding to the quaternary ammonium group containing the Y portion, preferably with 1,4-dimethylpiperazine, pyridine or 1-methylimidazole, to produce the quaternary polymer IV.

In a second step (b), the possible groups Protectants are removed by means of reactions such as reduction with hydrogenolysis (for example, in the presence of a black palladium catalyst), treatment with a hydrohalide acid such as hydrochloric, hydrobromic, hydrofluoric or hydroiodic acid, or treatment with trifluoroacetic acid. Preferably the treatment with 1M hydrochloric acid is used.

Method B Scheme II Scheme II shows the reaction of a monomer unit in polymer Ib containing a free amino group. The quaternary ammonium polymers of the formula VII ', wherein X2 and X3 are hydrogen or a quaternary group, and the other symbols have the meanings that were defined, can be prepared by condensing the amino group of intermediate Ib with a compound having the formula V or III as defined above, where Y 'is a group Y of quaternary ammonium, preferably with a mono- or di-quaternary piperazinium acid of the following formula: VTITa VÜIb where R2, R3, R, R5, m and Z are as defined above.

In formula Ib, P is independently H or a protecting group as defined above. In step c, compound VI 'is formed where P' has the meaning of a protecting group, hydrogen or X2 or X3. The reaction with compound V is carried out favorably in the presence of an activating agent, such as N, N'-dicyclohexylcarbodiimide and 1-hydroxybenzotriazole. The reaction is carried out in an inert solvent such as in aliphatic or aromatic hydrocarbons, preferably halogenated, alcohols, ethers, glycols, amides such as formamide, dimethylformamide or acetamide,? -methylpyrrolidone or tris- (dimethylamide) of phosphoric acid, acetonitrile, dimethyl sulphoxide and tetramethylene sulfone. Water can also be used as a solvent.

In a second step (d), the possible protective groups are removed as defined above.

When the protecting groups (P) are not used, it is possible that one or more of the functional groups X2 and X3 in the chitin and the chitosan are also substituted with a quaternary group, i.e. the degree of substitution for the X2 groups and X3 is independently 0-1, as discussed above.

Protective groups are needed when the quaternary substituents are to be regioselectively bound with primary or secondary hydroxyls, ie, X2 and X3 respectively. The amino group of the chitosan can be protected for example with a phthalimido moiety, the primary hydroxyl with a triphenylmethyl moiety and the secondary hydroxyl with an acetyl moiety (Macromolecules 24, 1991, 4745). All these protection groups can be conveniently unfolded and they allow the regioselective modification of chitosan (Macromolecules 24, 1991, 4745).

The starch, cellulose and other carbohydrate polymers containing hydroxyl groups can be converted to the quaternary polymer derivatives of the general formula (II) by means of esterification.

The esters can be prepared by the reaction of a carbohydrate polymer with a reactive carboxyl derivative of the formula (V): where A is any activation group and Y 'is a suitable leaving group, for example, chlorine, tosylate, iodine, etc., preferably bromine or chlorine, or is a Y-group of quaternary ammonium, R2, R3, m and Y are as were defined above, and when a compound is obtained as an intermediate containing a leaving Y 'group, the intermediate is further reacted with a tertiary or aromatic amine corresponding to the group Y, to produce the desired quaternary polymer.

The reactive carboxyl derivatives of the formula (V) include acid chlorides (A = Cl), acid anhydrides (A) t activated esters, activated amides.

Acid anhydrides include anhydrides symmetrical and acid anhydrides mixed. Active esters include p-nitrophenyl ester, ester with N-hydroxysuccinimide, etc. The activated amides include amide with imidazole. The carboxyl derivative can be activated using carbodiimides as activating agents, such as l-ethyl-3- (3-dimethylaminopropyl) -carbodiimide (EDC) or N ,? '-dicyclohexylcarbodiimide (DCC). In this method, the carbohydrate polymer and the carboxyl derivative are mixed in an aqueous or non-aqueous solvent with the carbodiimide reagent. The carboxyl derivative is converted to the corresponding urea, which reacts with the basic hydroxyl groups of the carbohydrate polymer to form ester bonds, respectively.

The acid chlorides can be prepared with thionyl chloride, oxalyl chloride, phosphorus trichloride or phosphorus pentachloride in the presence of an acceptor excess of acid such as triethylamine in a non-polar solvent such as hexane, dichloromethane, toluene or benzene. The acid chloride can be isolated or can be generated in situ.

Alternatively, the carboxyl group can be activated with ethyl chloroformate in the presence of triethylamine to produce a mixed anhydride, and this The latter is then reacted with the carbohydrate polymer to form amide or ester bonds.

When a carbohydrate polymer is reacted with the reactive carboxyl derivative shown in formula (V), the intermediate containing the leaving group Y 'is further reacted with a tertiary or aromatic amine corresponding to the group Y, preferably with 1-dimethylpiperazine, pyridine or 1-methylimidazole, to produce the quaternary polymer II.

For a revision of the cellulose and starch modification, reference is made to Prog. Polym. Sci 26, 2001, 1689, and Robyt J: Polysaccharides II. Chemical modifications and their applications. Essential of Carbohydrate Chemistry. Pages 228-244. Springer- Verlag, New York, 1998.

The following examples illustrate the invention, without limiting it.

EXAMPLES Characterization The 1H and 13C spectra were recorded in a Bruker AVANCE DRX 500 equipment, operating at 500.13 MHz and 125.76 MHz, respectively. The compounds were dissolved in D20 and 3- (trimethylsilyl) propionate-4 was used as an internal standard. The measurements were made at 300 K or 343 K. The 1H and 13C spectra separated from 1H were routinely recorded. For the XH spectrum, the recycling time was 4.6 s and 128 transients were collected. For the spectrum. { 1 HOUR} -13C, the recycling time was 5.2 s and 8192 transients were accumulated. The correlation experiments of simple XH enhanced gradient heteronuclear (ge-HSQC) were performed in the sensitive mode of the phase, using the TOOI gradient selection of Eco / Antieco. The FT-IR spectra were recorded on a Nicolet 510 P spectrometer for KBr pill.

Synthetic procedures A previously reported method (Macromolecules 37, 2004, 2784) was used to convert chitosan to 6-O-triphenylmethylchitosan, via N-phthaloylchitosan and N-phthaloyl-6-O-triphenylmethylchitosan. 6-0-Triphenylmethylchitosan (compound 4 in the Examples) or N-chloroacyl-6-O-triphenylmethylchitosans (1 to 17 in the Examples) were used as starting materials for the quaternization reactions. The N-chloroacyl-6-O- Triphenylmethylchitosans were prepared as described in Biomacromolecules 6, 2005, 858.

In the Examples that follow, of the polymer formulas, only one unit of reaction monomer is shown.

EXAMPLE 1 N- [1-carboxymethyl-2- (1,4-dimethylpiperazinium)] - chitosan chloride 2. a) ds 0.4: 1 g of N-chloroacetyl-6-O-triphenylmethylchitosan (1) (degree of N-chloroacetylation 0.4), 4.74 ml (35 mmol) of 1,4-dimethylpiperazine and 232 mg (1.4 mmol) of Kl were stirred in 50 ml of N-methylpyrrolidone under argon at 60 ° C for 72 h. The reaction mixture was cooled in ice water and the product was precipitated with diethyl ether and washed with methanol and diethyl ether. 2. b) ds 0.46: 1.4 g of N-chloroacetyl-6-O-triphenylmethylchitosan (1) (degree of N-chloroacetylation 0.46), 12.51 ml (92.5 mmol) of 1,4-dimethylpiperazine and 0.614 g (3.7 mmol) of Kl were stirred in 70 ml of N-methylpyrrolidone under argon at 60 ° C for 72 h. The reaction mixture was cooled in ice water and the product was precipitated with diethyl ether and washed with methanol and diethyl ether. 2. c) ds 0.85: 2 g of N-chloroacetyl-6-O-triphenylmethylchitosan (1) (degree of N-chloroacetylation 0.85), 24.3 ml (180 mmol) of 1,4-dimethylpiperazine and 1195 g (7.2 mmol) of Kl were stirred in 100 ml of N-methylpyrrolidone under argon at 60 ° C for 72 h. The reaction mixture was cooled in ice water and the product was precipitated with diethyl ether and washed with methanol and diethyl ether.

The 6-O-triphenylmethyl protection group was removed during a 3 hour reaction by stirring the compounds 2a-c with 1 M HCl at room temperature. The reaction mixture was evaporated to dryness and the product was washed with methanol and diethyl ether. The products were dialyzed against water at room temperature for 24 h and then dried frozen (ThermoSavantModulyoD-230, Savant, Holbrook, NY). 3. a) 730 mg of 2a produced 360 mg of 3a (94%). The degree of substitution determined by 1H NMR was 0.40. 3. b) 960 mg of 2b produced 387 mg of 3b (76%). The degree of substitution determined by 1H NMR was 0.46. 3. c) 1.35 g of 2c produced 720 mg of 3c (96%). The degree of substitution determined by XH NMR was 0.85. IR (KBr): v 3600-3100 (O-H), 3000-2700 (C-H), 1682 (amide I), 1565 (amide II), 1470 (C-N), 1150-950 CM "1 (C-O, pyranose). 1R NMR at 343K (D20): d 2.0 (CH3, N-acetyl), 2.4 (H-?), 2.8-3.0 (H-10), 3.0-3.1 (H-2, when the amino group is unsubstituted) , 3.3-3.4 (H-12), 3.4-3.9 (H-9, H-6, H-5, H-4, H-3, substituted H-2), 4.2 (H-8), 4.6-4.8 ppm (Hl). 13C? MR at 343K (D20): d 25.0 (CH3, N-acetyl), 46.5 (C-ll), 50.3 (C-10), 51.4 (C-12), 58.4 (C-2, substituted), 59.1 (C-2, unsubstituted), 63.1 (C-6, substituted), 63.3 (C-6, unsubstituted), 63.8 (C-9), 63.9 (C-9), 65.3 (C-8), 74.7 (C-3), 77.7 (C-5), 80.5 (C-4 unsubstituted), 81.4 (C-4, substituted), 102.9 (Cl, substituted ), 104.0 (Cl, unsubstituted), 167.0 (C-7), 177.1 ppm (C = 0, N-acetyl).

EXAMPLE 2 [N- [1-carboxymethyl-2- (4,4-dimethylpiperazinium)] - chitosan chloride The preparation of 4-carboxymethyl-1, 1-dimethylpiperazinium iodide is described in Example 9.

General procedure . 1 g of 6-0-triphenylmethyl chitosan (4) (content of free amino group of 2.074 mmol) was dissolved in 50 mL of N-methylpyrrolidone. 4-carboxymethyl-l, 1-dimethylpiperazinium iodide, 1-hydroxybenzotriazole and N, were dissolved. '-dicyclohexylcarbodiimide in 20 mL of N-methylpyrrolidone. The solutions were combined and stirred at room temperature under argon for 96 hours. The products were precipitated with diethyl ether and washed with methanol and diethyl ether. . a) Amounts of reagents used: 214 mg (0.713 mmol) of 4-carboxymethyl-l, 1-dimethylpiperazinium iodide (0.34 equiv), 110 mg (0.814 mmol, 0.39 equiv) of 1-hydroxybenzotriazole and 171 mg (0.829 mol, 0.40 equiv) of N, N '- dicyclohexylcarbodiimide. 674 mg (61%) of the product 5a was obtained. . b) Amounts of reagents used: 410 mg (1.366 mmol, 0.66 equiv) of 4-carboxymethyl-l, 1-dimethylpiperazinium iodide, 219 mg (1620 mmol, 0.78 equiv) of 1-hydroxybenzotriazole and 337 mg (1.633 mmol, 0.79 equiv) of N ,? '-dicyclohexylcarbodiimide. 897 mg (70%) of product 5b was obtained. . c) Amounts of reagents used: 828 mg (2.759 mmol, 1.33 equiv) of 4-carboxymethyl-l, 1-dimethylpiperazinium iodide, 447 mg (3.241 mmol, 1.56 equiv) of 1-hydroxybenzotriazole and 677 mg (3.281 mmol, 1.582 equiv) of?,? ' -dicyclohexylcarbodiimide. 1,714 g (100%) of the product 5c were obtained.

The 6-O-triphenylmethyl protection group was removed during a 3 hour reaction by stirring compounds 5a-c with 1M HCl at room temperature. The reaction mixture was evaporated to dryness and the product was washed with methanol and diethyl ether. The products were dialyzed against water at room temperature for 24 h and then dried frozen (ThermoSavantModulyoD-230, Savant, Holbrook, NY). 6. a) 650 mg of 5a produced 269 mg of 6a (82%) The degree of substitution determined by 1H NMR was 0.15. 6. b) 880 mg of 5b produced 329 mg of 6b (71%) The degree of substitution determined by 1H NMR was 0.42. 6. c) 1.61 g of 5c produced 550 mg of 6c (61%) The degree of substitution determined by 1H NMR was 0.87.

IR (KBr): v 3600-3100 (O-H), 3000-2700 (C-H), 1658 (amide I), 1534 (amide II), 1475 (C-N), 1150-950 cm "1 (C-O, pyranose). XH NMR at 343K (D20): d 2.0 (CH3, N-acetyl), 2.9-3.0 (H-9), 3.0-3.1 (H-2, when the amino group is unsubstituted), 3.1-3.2 (H- ll, H-12), 3.25-3.5 (H-8), 3.45-3.8 (H-10), 3.5-3.7 (H-5), 3.6-4.0 (H-6), 3.55-3.7 (H-4) , substituted), 3.6-3.8 (H-3), 3.7-3.9 (H-2, substituted), 3.75-3.9 (H-4, unsubstituted), 4.6 to 8 ppm (H-1). 13C NMR at 343K (D20): d 25.0 (CH3, N-acetyl), 49.0 (C-9), 54.4 (C-11, C-12), 58.0 (C-2, substituted), 59.1 (C-2) , unsubstituted), 61.9 (C-8), 63.0 (C-6, substituted), 63.3 (C-6, not substituted), 64.3 (C-10), 74.3 (C-3, no replaced), 74.7 (C-3, substituted), 77.4 (C-5, substituted), 77.7 (C-5, unsubstituted), 80.9 (C-4 unsubstituted), 81.8 (C-4, substituted), 102.1 (CI, unsubstituted), 103.4 (Cl, substituted), 175.2 (C-7), 177.2 ppm (C = 0, N-acetyl).

EXAMPLE 3 - [l-carboxymethyl-2- (1,4,4-trimethylpiperazi- 1,4-dio)] chitosan dichloride The preparation of 1-carboxymethyl-1,4-trimethylpiperazyl-1-diiodide is described in Example 9.

GENERAL PROCEDURE . of 6-0-triphenylmethylchitosan (4) (content of free amino group of 2.074 mmol) was dissolved in 50 mL of N-methylpyrrolidone. 1-Carboxymethyl-l, 4, 4-trimethylpiperaz-1,4-dio, 1-hydroxybenzotriazole diiodide and W ^? '- were dissolved. dicyclohexylcarbodiimide in 20 mL of N-methylpyrrolidone. The solutions were combined and stirred at room temperature under argon for 96 hours. The products were precipitated with diethyl ether and washed with methanol and diethyl ether. 7. a) Amounts of reagents used: 473 mg (1.07 mmol) 1-carboxymethyl-1,4,4-trimethylpiperaz-1,4-dio diiodide (0.52 equivalents compared to the free amino group in 6-O-triphenylmethylchitosan), 173 mg (1.28 mmol, 0.62 equiv) of 1-hydroxybenzotriazole and 264 mg (1.28 mmol, 0.62 equiv) of N ,? '-dicyclohexylcarbodiimide. 1.08 g (87%) of the product 7a was obtained. 7. b) Amounts of reagents used: 941 mg (2.13 mmol, 1.03 equiv) of 1-carboxymethyl-1,4,4-trimethylpiperaci-1,4-dio, 346 mg (2.56 mmol, 1.23 equiv) 1-hydroxybenzotriazole diiodide and 528 mg (2.56 mmol, 1.23 equiv) of N ,? '-dicyclohexylcarbodiimide. 1.29 g (93%) of product 7b were obtained. 7. c) Amounts of reagents used: 1,883 mg (4.26 mmol, 2.05 equiv) of 1-carboxymethyl-1,4,4-trimethylpiperazyl-4-dio dioxide, 691 mg (5.11 mmol, 2.46 equiv) of 1-hydroxybenzotriazole and 1054 g (5.11 mmol, 2.46 equiv) of N, N'-dicyclohexylcarbodiimide. 1.71 g (100%) of product 7c were obtained.

The 6-O-triphenylmethyl protection group was removed during a 3 hour reaction by stirring the compounds 7a-c with 1M HCl at room temperature. The reaction mixture was evaporated to dryness and the product was washed with methanol and diethyl ether. The products were dialyzed against water at room temperature for 24 hours and dried frozen (ThermoSavantModulyoD-230, Savant, Holbrook,? Y). 8. a) 1.08 g of 7a produced 460 mg of 8a (81%). The degree of substitution determined by 1H? MR was 0.34. 8. b) 1.29 g of 7b produced 590 mg of 8b (84%). The degree of substitution determined by "" "H? MR was 0.54. 8. c) 1.71 g of 7c produced 640 mg of 8c (68%). The degree of substitution determined by 1H? MR was 0.65.

IR (KBr): v 3600-3100 (OH), 3000-2700 (CH), 1682 (amide I), 1563 (amide II), 1481 (C-?), 1150-950 cm "1 (CO, pyranose) 1ti? MR to 343K (D20): d 2.0 (CH3, N-acetyl), 3.0-3.1 (H-2, when the amino group is not substituted), 3.4-3.6 (H-ll, H-12), 3.5-3.6 (H-13), 3.55-3.8 (H-5), 3.6-4.0 (H-6), 3.6-3.9 (H-4) ), 3.65-3.8 (H-3), 3.7-4.5 (H-9, H-10), 3.7-3.8 (H-2, substituted), 4.3-4.4 (H-8), 4.6-4.8 ppm (HI) ). 13C NMR at 343K (D20): d 25.0 (CH3, N-acetyl), 52.0 (C-13), 53.7 (C-ll), 56.9 (C-12), 57.9 and 58.1 (C-9), 58.4 ( C-10), 58.9 (C-2, substituted), 59.0 (C-2, unsubstituted), 63.4 (C-6), 65.6 (C-8), 63.3, 74.4 (C-3), 77.7 (C -5), 80.9 (C-4), 102.2 (Cl, unsubstituted), 102.8 (Cl, substituted), 166.5 (C-7), 177.1 ppm (C = 0, N-acetyl).

EXAMPLE 4. N- (l-carboxymethyl-2-pyridinium) chitosan chitosan 300 mg of N-chloroacetyl-6-O-triphenylmethyl chitosan (1) (N-chloroacetylation grade 0.85) were stirred in 10 ml of pyridine under argon at 60 ° C for 72 h. The solvent was evaporated and the product was washed with methanol and diethyl ether. The relative production of product 9 was 176 mg (51%).

The 6-0-triphenimethyl protection group was removed during a 3 hour reaction by stirring 170 mg of compound 9 with 20 ml of 1M HCl at room temperature. The reaction mixture was evaporated to dryness and the product was washed with methanol and diethyl ether. The degree of substitution calculated for the 1h nmr spectrum was 0.85. The production of the product (10) was 63 mg (65%). IR (KBr): v 3600-3100 (O-H), 3100-3000 (CH, pyridyl), 2950-2700 (CH), 1687 (amide I), 1559 (amide II), 1490 (C = C, pyridyl), 1374 (C = C, pyridyl), 1150-950 (CO, pyranose), 783 (arom, pyridyl), 725 (arom, pyridyl), 677 cm "1 (arom, pyridyl). 1 H NMR at 300K (D20): d 2.0 (CH3, N-acetyl), 3.5- 3.6 (H-5), 3.7-4.0 (H-6), 3.7- 3.8 (H-4), 3.8-4.0 (H-3), 3.85-4.0 (H-2), 4.7-4.8 (HI), 5.5-5.7 (H-8), 8.1-8.2 (H-10), 8.65- 8.75 (H-ll), 8.75-8.9 ppm (H-9) .13C? MR at 300K (D20): d 25.0 (CH3) , N-acetyl), 58.8 (C-2), 63.0 (C-6), 64.6 (C-8), 74.7 (C-3), 77.6 (C-5), 81.1 (C-4), 103.3 ( Cl), 131.0 (C-10), 148.6 (C-9), 149.8 (C-ll) 169.4 ppm (C-7).

EXAMPLE 5? - [l-Carboxymethyl-2 (1-methylimidazolium)] Chitosan Chloride 295 mg of N-chloroacetyl-6-O-triphenylmethylchitosan (1) (N-chloroacetylation grade 0.85) were stirred in 10 ml of 1-methylimidazole under argon at 60 ° C for 72 h. The reaction mixture was evaporated to dryness and the product was washed with methanol and diethyl ether. The relative production of product 11 was 116 mg (34%).

The protection group 6-trifenimethyl was removed during a 3 hour reaction by shaking 105 mg of compound 11 with 15 ml of 1M HCl at room temperature. The reaction mixture was evaporated to dryness and the product was washed with methanol and diethyl ether. The calculated degree of substitution of the 1H? MR spectrum was 0.85. The production of the product (12) was 45 mg (77%). IR (KBr): v 3600-3100 (O-H), 3100-3000 (C-H, imidazole), 2950-2700 (C-H), 1685 (amide I), 1560 (amide II), 1375 (C = C, imidazole), 1150-950. 1ti? MR at 300K (D20): d 2.1 (CH3, N-acetyl), 3.5-3.6 (H-5), 3.6-3.9 (H-6), 3.6- -3.8 (H-4), 3.7-3.9 (H-3), 3.8-3.9 (H-2), 3.9-4.0 (H-12), 4.6-4.8 (H-) 1), 5.1-5.3 (H-8), 7.50 (H-ll), 7.52 (H-10), 8.75-8.85 ppm (H-9). 13C NMR at 300K (D20): d 25.0 (CH3, n-acetyl), 38.8 (C-12), 53.6 (C-8), 58.6 (C-2), 63.0 (C-6), 74.7 (C-) 3), 77.6 (C-5), 81.3 (C-4), 103.4 (Cl), 126.3 (C-11), 126.5 (C-10), 140.3 (C-9) 170.5 ppm (C-7).

EXAMPLE 6. Chloride of 27- (l-carboxybutyl-4-pyridinium) chitosan 220 mg of N-chlorobutyryl-6-O-triphenylmethylchitosan (17) (N-chlorobutyrylation degree of 0.67) were stirred in 8 ml of pyridine under argon at 60 ° C for 72 h. The solvent was evaporated and the product was washed with methanol and diethyl ether. The relative production of 18 was 140 mg (57%).

The 6-O-triphenylmethyl protection group was removed during a 3 hour reaction by shaking 140 mg of compound 18 with 14 ml of 1M HCl at room temperature. The reaction mixture was evaporated to dryness and the product was washed with methanol and diethyl ether. The degree of substitution of 19 calculated from the 1H NMR spectrum was 0.67. The production of the product (19) was 44 mg (56%). IR (KBr): v 3600-3100 (OH), 3000-2700 (CH), 1655 (amide I), 1554 (amide II), 1489 (C = C), 1150-950 cm "1 (C-0, pyranose). XH NMR A 343K (D20):? 2.0 (CH3, N-acetyl), 2.3-2.4 (H-9), 2.4-2.5 (H-8), 3.1-3.2 (H-2, when the group amino is unsubstituted), 3.4-3.9 (H-6, H-5, H-4, H-3, substituted H-2), 4.5-4.6 (Hl, substituted), 4.6- 4.7 (H-10), 4.8-4.9 (Hl, unsubstituted), 8.1-8.2 (H-12), 8.5-8.6 (H-13), 8.8-8.9 ppm (H-ll) .13C? MR A 343K (D20): d 25.1 ( CH3, N-acetyl), 29.1 (C-9), 34.8 (C-8), 58.2 (C-2, substituted), 58.8 (C-2, unsubstituted), 63.2 (C-6, substituted), 63.4 (C-6, unsubstituted), 63.7 (C-10), 73.5 (C-3, unsubstituted), 74.9 (C-3, substituted), 77.6 (C-5, substituted), 78.1 (C-5, unsubstituted), 80.2 (unsubstituted C-4), 82.2 (C-4, substituted), 100.5 (Cl, unsubstituted), 103.8 (Cl, substituted), 131.3 (C-12), 147.0 (C-13) , 148.8 (C-IL), 177.3 (C-7).

EXAMPLE 7 Quaternary piperazinium acids 22 24 1- (2-Ethoxy-2-oxoethyl) -4-methylpiperazine (20) was prepared from 1-methylpiperazine and ethylbromoacetate as described in the Journal of Medicinal Chemistry 43, 2000, 1489. When the compound (20) had reacted with Mel in dry acetonitrile, 1- (2-ethoxy-2-oxoethyl) -1,4,4-trimethylpiperazi- 1,4-dio (21) diiodide was precipitated as a pure compound and the 4- (2-ethoxy-2-oxoethyl) -1,1-dimethylpiperazinium (22) iodide remained in solution. 6.96 g (37.37 mmol) of l- (2-ethoxy-2-oxoethyl) -4-methylpiperazine (20) and 9.3 ml (149 mmol, 4 equiv) of Mel were reacted in 270 ml of ACN for 48 h. The precipitate was filtered and washed with acetonitrile. The precipitate produced 2,354 g (13%) of 1- (2-ethoxy-2-oxoethyl) -1,4-trimethylpiperaz-1,4-dio (21) diiodide. The filtrate was evaporated to dryness and the iodide yield of 4- (2-ethoxy-2-oxoethyl) -1,1-dimethylpiperazinium (22) was 9998 g (82%). This reaction was repeated with 7.8 g (41.9 mmol) of 1- (2-ethoxy-2-oxoethyl) - 4-methylpiperazine (20) and 26.1 ml (420 mmol, 10 equiv) of Mel. The reaction proceeded in 300 ml of ACN for 240 h. The precipitate was filtered and washed with acetonitrile. The precipitate produced 11124 g (57%) of l- (2-ethoxy-2-oxoethyl) -1,4,4-trimethylpiperazyl-di (21) diiodide. The filtrate was evaporated to dryness and the iodide yield of 4- (2-ethoxy-2-oxoethyl) -1,1-dimethylpiperazinium (22) was 5.82 g (42.2%). 1- (2-Ethoxy-2-oxoethyl) -1,4,4-trimethylpiperazyl, 4-dio (21): 1ti NMR at 300K (D20): d 1.33 Diiodide (2H, t, J = 14 Hz), 3.44 (3H, s), 3.47 (3H, s), 3.59 (3H, s), 3.9-4.3 (8H, bm), 4.37 (2H, q, J = 14 Hz), 4.67 (2H, d) 13C NMR at 343K (D20): d 16.03, 51.89, 53.60, 57.01, 57.75 (2C), 58.27 (2C), 58.49, 67.08, 167.03 4- (2-Ethoxy-2-oxoethyl) -1,1-dimethylpiperazinium iodide (22): 1 H NMR at 300K (D20): d 1.28 (2H, t, J = 14 Hz), 3.01 (4H, s) , 3.21 (6H, s), 3.49 (4H, s), 3.51 (2H, s), 4.24 (2H, q, J = 14 Hz) 13C NMR at 343K (D20): d 16.18, 48.58 (2C), 54.50 (2C), 60.04 (2C), 64.25, 64.98, 174.44.

The ethyl ester groups were split by refluxing compounds 21 and 22 in water. 1-Carboxymethyl-l, 4, 4-trimethylpiperazyl, 4-dio (23) diiodide. 8.5 g of 1- (2-ethoxy-2-oxoethyl) -1,4,4-trimethylpiperazyl-4-dio (21) was refluxed in 700 ml of water for 96 h. The reaction mixture was evaporated to dryness and the procedure was repeated. The product was washed with acetone and crystallized with ethanol from water. A white powder was produced, 4.98 g (62%). 1 H NMR at 300K (D20): d 3.41 (3H, s), 3.43 (3H, s), 3.49 (3H, s), 3.9-4.1 (6H, bm), 4.35 (2H, s), 4.4-4.5 ( 2H, bm) 13C NMR at 343K (D20): d 51.79, 53.45, 56.85 (3C), 58.44 (2C), 66.58, 169.53. 4-carboxymethyl-l, 1-dimethylpiperazine iodide (24) 11.77 g of 4- (2-ethoxy-2-oxoethyl) -1,1-dimethylpiperazinium iodide (22) were refluxed in 600 ml of water for 48 h. The reaction mixture was evaporated to dryness and the product was crystallized with diethyl ether from ethanol. A white powder was produced, 5,484 g (51%). XH NMR at 300K (D20): d 3.30 (6H, s), 3.51 (4H, s), 3.69 (2H, s), 3.73 (4H, bm). 13C NMR at 343K (D20): d 48.86 (2C), 54.84 (2C), 60.47, 62.74 (2C), 173.72.

Claims (10)

1. Quaternary polymers that have the general formula: where T is NH or 0; Xi, X2 and X3 are, independently, H o: O R2 m in the case that T is NH (ie, chitin and chitosan), Xi, X2 and X3 can also be: and, in addition, Xi can also be: fl -C-CH3 wherein R and R are independently H or a substituted or unsubstituted, straight or branched alkyl chain with 1 to 6 carbon atoms, and m is an integer from 1 to 12, Y is a quaternary ammonium moiety selected from piperazine portions having the formula: (A) (B) (C) or selected from among the groups: (D) (E) wherein R and R5 are independently a substituted or unsubstituted, straight or branched alkyl chain having from 1 to 6 carbon atoms, Z is a negatively charged counterion, preferably selected from the group consisting of Cl " , Br ", I", OH "R? COO", R? S04", where Ri is H or an alkyl group with 1 to 6 carbon atoms or an aromatic portion, where the degree of substitution (ds) of the substituent Quaternary for the total of groups Xi, X2 and X3 is at least 0.01, n is the degree of polymerization, and can be an integer from 2 to 100,000, with the proviso that, when T is O, Y can only have the meaning of a group of the formula (A), (B), (C) or (E) as defined.

2. The polymers according to claim 1, characterized in that, T is NH, Xi, X2 and X3 are as defined in claim 1, and Y is one of the groups having the formulas (A), (B) or (C), wherein the degree of substitution of the quaternary group is from 0.01 to 1, preferably from 0.05 to 1.

3. The polymers according to claim 1, characterized in that T is NH, X2 and X3 are hydrogen and Xi is hydrogen, acetyl or a group containing a portion of quaternary ammonium as defined in claim 1, especially one of the groups having the formulas (A) to (E), and in particular the formulas (A), (B) or (C), and the degree of substitution of the quaternary group is on the scale from 0.01 to 1, preferably from 0.05 to 1.

4. The polymers according to claim 1 , characterized in that T is O, Xi, X2 and X3 are hydrogen or a group containing a portion of quaternary ammonium as defined in claim 1, and where Y is one of the groups having the formulas (A), ( B), (C) or (E), and where the degree of substitution of the quaternary group is on the scale of 0.01 to 1, preferable 0.05 to 1.

5. Process for the preparation of the quaternary polymers according to formula (I) in claim 1, according to which: I) for the preparation of a compound wherein T is NH, a) a chitin or chitosan derivative having a free amino or hydroxyl group is reacted, and where the remaining reactive groups are optionally in protected form, with a compound that has the formula V: where A is an activation group, Y 'is a suitable leaving group or is a quaternary ammonium group Y, m and Y are as defined in claim 1, or with a compound having the formula III: where L is a leaving group, and Y 'is either a quaternary ammonium Y group or a suitable leaving group, and R2, R3, m and Y are as defined above, whereby L is a leaving reagent group as good as , or better than, or more reactive, compared to a leaving group Y ', and where an intermediate compound containing a leaving group Y' is obtained, the intermediate is then reacted with a tertiary or aromatic amine corresponding to the ammonium group Y quaternary, to produce the desired quaternary polymer, and then remove any protecting groups, or b) for the preparation of a chitin or chitosan derivative having an amino group substituted with a group Xi containing a quaternary ammonium group, and X2 and X3 are hydrogen, a polymer of chitin or chitosan in which the hydroxyl groups in positions 3 and / or 6 are optionally protected, and the amino group in one or more of the monomer units of the polymer carries an alkyl or alkyloxy group corresponding to group Xi where the group Y is replaced by a suitable leaving group, is reacted with a tertiary or aromatic amine corresponding to the group And quaternary ammonium, and remove any protecting groups, or c) for the preparation of a chitin or chitosan derivative having an amino group 'substituted with a group Xi containing a quaternary ammonium group, a chitin polymer or chitosan having a free amino group and in which the hydroxyl groups in the 3 and / or 6 positions are optionally protected, is reacted with a compound having the formula III or the V as defined above, and when Y 'in the formula III or V is a leaving group, reacting the intermediate compound thus obtained with a tertiary or aromatic amine corresponding to the group Y, and removing any protective groups, thereby a compound obtained in which Xi / X2 and / or X3 have the meaning of hydrogen, can be converted to a compound in which Xi, X2 and / or X3 are different from hydrogen, by reacting them with a compound of formula III or V As defined above, and reacting an intermediate like this obtained containing a leaving group Y 'with a tertiary or aromatic amine corresponding to the Y group of quaternary ammonium, and removing any protecting groups optionally used in the reaction, or II. For the preparation of a compound wherein T is O, esterify a carbohydrate polymer containing at least one unprotected hydroxyl group with a reactive carboxyl derivative having the formula: where A is an activation group, Y 'is a suitable leaving group or Y, R2, R3, m and Y are as defined in claim 1, and when a compound is obtained as an intermediate containing a leaving group Y', the intermediate is furthermore reacted with a tertiary or aromatic amine corresponding to the group Y, to produce the desired quaternary polymer, and remove any protective group from a compound obtained, and, if desired, convert a compound obtained in which Xi, X2 and / or X3 are hydrogen, to a compound in which Xi, X2 and / or X3 are different from hydrogen, by means of reacting it with a compound of the formula V, and in the case where a compound is obtained as an intermediate that contains a leaving group, to react the intermediary with a tertiary or aromatic amine corresponding to the Y group of quaternary ammonium, and removing any protecting groups optionally used in the reaction.

6. Piperazinium mono- and di-quaternary acids, of the formula: vpv where R2, R3, R4, R5, m and Z "are as defined in accordance with claim 1.

7. Process for preparing the mono- and di-quaternary piperazinium acids as defined in claim 6, in accordance with which, a compound that has the formula: X where R2, R3, R4 and m have the meaning given above and E is hydrogen or any group commonly used to protect the carboxyl portion, preferably ethyl, is reacted with a quaternized compound corresponding to the group R5, such as a alkyl halide, alkyl fluorosulfo, dialkyl sulfate, alkyl tosylate, or suitable alkyl mesylate, to form a mixture of the compounds having the formulas: Vina * VDTb 'where R2, R3, R4, R5, my E have the meaning given above, separating the compounds afterwards and, if necessary, converting the thus separated compounds into their corresponding acids, and optionally converting the acid in a salt.

8. Process according to claim 7, characterized in that the separation of the two compounds is carried out by precipitating one of the two compounds by the appropriate choice of the solvent, whereby the other compound will remain in solution.

9. Process according to claim 7 or 8, characterized in that the Villa 'di-quaternized compound is precipitated, and the mono-quaternized compound VlIIb' remains in solution.

10. Process according to claim 9, characterized in that the solvent is acetonitrile.