MALEIC COPOLYMER

The maleic copolymer, sulfonated styrene maleic anhydride... 

Maleic anhydride (1.17 Mt/a world installed capacity) finds its major use in the synthesis of unsaturated polyester resins ca. 41%), with the remainder going to produce butanediol (14%), maleic copolymers (8%), tetrahydrofuran (7%),... 

Maleic anhydride (MA) is an important intermediate in the production of chemicals such as unsaturated polyester resins, lube oil additives, maleic copolymers and others [124]. Currently, MA is predominantly produced by the oxidation of butane, and all industrial catalysts for this reachon are based on vanadium phos-... 

Adhesive compositions for reducing, inhibiting and/or preventing calculus, tartar, plaque and/or microbes in the oral cavity comprise from about 15 to 70% of an alkyl vinyl ether maleic copolymer or terpolymer denture adhesive component, an effective amount of a quaternary ammoiuum antimicrobial agent selected from the group consisting of cetylpy ridinium chloride, domiphenbromide or mixtures thereof, and a non-aqueous vehicle. 

Polymeric polyelectrolytes have also found applications as alternative builder ingredients [96,97], High-molecular-weight polyacrylate homopolymers and acrylic-maleic copolymers can be very effective in tying up calcium ions in the... 

For instance, maleic copolymers with different contents of galactose moieties and dodecyl chains were synthesized and used as both a stabilizer and a surface coating for the preparation of poly(s-caprolactone) nanoparticles by the emulsification-diffusion technique. The smface modification of nanoparticles was confirmed by -potential measurements. Nanoparticles were also shown to be recognized by a galactose-specific lectin, demonstrating the presence of galactose rmits on the particle surface [69],... 

Pomarez, Olefin/maleic copolymers. Baker Petrolite, Polymers Div. 

In this chapter, we intend to present the obtaining and properties of new types of nanocomposites based on natural polymer (collagen) and bioactive compounds (natural layered silicate modified with maleic copolymers) which can be used as biomateiial, scaffold for bone tissue regeneration. 

Binary nanocomposites of layered sihcate/ maleic copolymers can contain different bioactive substances which can be released in time and at low and controlled concentrations (bone growth factors, titania or carbon aerogels, hydrolyzed collagen, anticancer compounds, antimicrobial antioxidants, etc.). 

Maleic copolymers having variable hydrophobicity (maleic anhydride copolymers with a hydrophilic comonomer - vinyl acetate and a hydrophobic comonomer - methyl methacrylate), are obtained in anhydrous form by "Petru Poni" Institute of Macromolecular... 

The chemical structures of maleic copolymers used are presented in Fig. 1 and 2. 

The characteristics of MA-MMA maleic copolymers with hydrophobic comonomer and of MA-VA maleic copolymers with hydrophilic comonomer are presented in Table 1. 

Physical-chemical and structural properties of purified layered silicate, of binary nanocomposites based on layered silicate/ maleic copolymers and of ternary nanocomposites of collagen/layered silicate/maleic copolymers are determined by using different techniques described below. 

By introducing maleic copolymers as structural modifiers of layered silicates leads to binary stable hybrids compatible with collagen gel, a process which forms a hquid ternary nanocomposite resistant to further processing, for example to lyophilization. 

Layered silicate/maleic copolymers binary nanocomposites... 

The natural layered silicate/maleic copolymer binary nanocomposites are obtained by solution intercalation method (Ray Okamoto, 2003). According to the chemical structme of maleic partner, the interaction between inorganic and organic components is performed at different ratios (1 1 1 2 and 2 1), in a mixture of 1 1 ethanol- water. Thus, we obtain maleic copolymer modified layered silicate binary nanocomposites PB/ MA-MMA (1 1 1 2 and 2 1) and PB/ MA-VA (1 1 1 2 and 2 1). 

From X-ray diffractions (Fig. 7 and 8) we notice that silicate structure changes in a specific way a peak disappears at 2 0 = 23°, which is silicate characteristic peak and shapes very well the peak at approximately 2 0 = 3°. This proves the interaction between sihcate and maleic copolymers as well as an organized structure. Intercalated nanocomposites are obtained with a lamellar ordered structure. Maleic copolymer with hydrophobic comonomer (MA-MMA) interacts better with silicate, the best structure is obtained at 1 1 silicate/copolymer ratio. In the case of maleic copolymer with hydrophilic comonomer (MA-VA), the best structure is obtained at a low amount of copolymer, meaning at 2 1 ratio. These two types of layered silicate/ maleic copolymer binary nanocomposites are selected to obtain ternary nanocomposites. 

As compared to purified bentonite, at which the maximum rate of decomposition is on the first step, at a temperature of 74 °C, the organophilized bentonite presents a shift of maximum decomposition rate towards higher temperatures (220-5-225°C for PB/ MA-VA nanocomposites and 220 -5-365 °C for PB/ MA-MMA nanocomposites), on the second step of decomposition, similar to maleic copolymers (Table 3). An increase of maleic copolymer concentration (from 50% to approximately 200% reported to bentonite) reflects into an increase of weight loss at the temperature range of 200 500 °C. The obtained results show the intercalation of maleic copolymers between the silicate layers. Thermal stability of obtained binary nanocomposites correlates with the degree of interaction between silicate and copolymer. We notice that in the case of PB/ MA-MMA nanocomposites the best thermal stability is obtained at 1 1 ratio while the best thermal stability for the PB/ MA-VA nanocomposites is obtained at 2 1 ratio. These results are in accordance with X-ray diffraction results. 

Table 3. TGA results for PB/ Maleic copwlymer binary nanocompwsites as compared to TGA results for maleic copolymers (MA-MMA and MA-VA).

Collagen/ layered silicate/ maleic copolymer nanocomposites... 

The authors are gratefully acknowledged for their collaboration with C. Radovici for XRD, C. Nistor for DLS and S. Serban for TGA from National Research and Development Institute for Chemistry and Petrochemistiy-ICECHIM, Bucharest and to "Petru Poni" Institute of Macromolecular Chemistry, Romanian Academy, Iasi team which provided maleic copolymers. 

Keywords Maleic copolymers, controlled water solubility, antitumor activity, DIVEMA, male contraception, RISUG, protein conjugates, SMANCS, drug delivery systems... 

The copolymers obtained by radical copolymerization of maleic anhydride (MA) with acrylic or vinyl comonomers, and the maleic add copolymers, generally obtained by the hydrolysis of the maleic anhydride copolymers (Figure 10.1), can be called maleic copolymers. They were intensively studied from a theoretical perspective, but also for their applications [1-3]. Copolymers ofMA with electron-donating comonomers, such as styrene, vinyl acetate, N-vinyl pyrrolidone, and methyl vinyl ether, have an alternant structure [ 1 ], but when MA is copolymerized with electron-acceptor comonomers like methyl methacrylate, acrylonitrile, statistic copolymers are obtained [1,2]. MA units from the copolymers are very reactive active agents with amine or hydroxyl groups... 

Pharmaceutical applications of maleic copolymers are favored by several properties such as biocompatibility, generally well-defined structure, the possibility to vary the hydrophilic/hydrophobic balance by the proper choice of comonomer or by further chemical reactions on the copolymer, and solubility in organic media when the copolymers are in anhydride form and in water when they are in acid/salt form. The reactivity of the maleic anhydride cycle offers the possibility to bind drugs, protein, or enzymes to the copolymer chain. The obtained conjugation products also have a carboxylic add group that can confer water solubility and pH sensibility. 

Maleic copolymers with methyl vinyl ether, N-vinyl-pyrrolidone, styrene, vinyl acetate, divinyl ether, were proved to be biocompatible [6-11], but the impurities (solvent traces, unreacted monomers, oligomers) need to be removed by advanced purification [12], Molar mass also influences the toxidty polymers with relatively high molar mass cannot be eliminated renally and accumulate in the body, inducing toxic reactions [6,13]. On the other hand, high molar mass is required for the biological activity of the polymer, which is why a proper choice of molar mass and a narrow distribution are needed in order to provide reduced toxicity together with efficiency [6,14]. 

Figure 10.3 Chemical structure of maleic copolymers with perse biological activity.

Another method to improve the incorporation of bioactive polymers into the cells is the grafting of hydrophobic groups on the polymer, which improves the affinity for the cell membrane. Maleic copolymers are good candidates for such modifications, the anhydride cycle being easily reacted with hydrophobic amines. Poly(MA-St), poly(MA-CDA) and poly(maleic anhydride-alt-3,4-dihydroxyphenylprop-l-ene) modified with alkyl amines or aniline were proved to perturb the liposome membrane and to interact with epithelial cells or DMSO-differentiated HL-60 cells [48-50]. As a result, the biological activity, evaluated by the ability to simulate the release of superoxide anion by the cells, was enhanced when the polymer was modified with hydrophobic units [49]. 

Maleic copolymers are proper candidates for the conjugation with therapeutic agents due to their anhydride cycle that can easily react with -NH, -OH or -SH groups. The carboxylic groups obtained after these reactions or by subsequent hydrolysis, can offer water solubility and pH sensitivity to the obtained conjugates. 

The NCS was also modified with DIVEMA copolymer. The in-vivo toxicity of the resulting conjugate was reduced, but the EPR effect was not observed. This was explained by the hydrophilicity of DIVEMA that did not favor the binding with albumin which would increase the apparent size, as in the case of SMANCS [103]. Some efforts were also made in order to obtain a conjugate of tumor necrosis factor with DIVEMA copolymer [104]. In this case, several free amino groups of the protein need to be protected before the reaction with the maleic copolymer. In the in-vivo test, the conjugate had a much higher antitumor effect than the native tumor necrosis factor. 

Table 10.1. Conjugates of therapeutic agent and maleic copolymers...

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