RU2757499C1 - Chitosan modification method - Google Patents

Abstract

FIELD: polymer chemistry.

SUBSTANCE: invention relates to the field of polymer chemistry. The method for modifying chitosan involves the synthesis of a copolymer containing oxirane fragments in the presence of azobisisobutyronitrile and grafting of the copolymer to chitosan. Grafting of the copolymer is carried out by keeping chitosan in the form of chitosan films or spongy material, previously obtained in acetic acid solutions, at 20°С for 30 minutes in a 1.5-7.5 wt.% solution of a previously prepared copolymer of glycidyl methacrylate and hexyl methacrylate selected from the series, n-decyl methacrylate, lauryl methacrylate, tetradecyl methacrylate, stearyl methacrylate derivative of methacrylate in methyl ethyl ketone, taken in a molar ratio of monomers equal to 4:1. Then, the modified chitosan is thermostated at 140°С for 1 hour and the unreacted copolymer is washed from the unreacted copolymer by extraction in a Soxhlet apparatus using methyl ethyl ketone as an extractant for 4 hours.

EFFECT: invention is aimed at increasing the hydrophobicity of materials based on chitosan while maintaining their biodegradability and biocompatibility.

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Description

The invention relates to the field of polymer chemistry, in particular to the modification of the natural polymer of chitosan, and can be used in the fields of medicine, cosmetics, food industry, biotechnology, wastewater treatment.

A known method of emulsion-free graft copolymerization of chitosan with n-butyl acrylate by the free radical mechanism [Chitosan-graft-poly (n-butyl acrylate) copolymer: Synthesis and characterization of a natural / synthetic hybrid material / P. Anbinder, C. Macchi, J Amalvy, A. Somoza // Carbohydrate polymers. - 2016. - Vol. 145. - P. 86-94]. The graft copolymerization was carried out in a 1% aqueous solution of acetic acid using potassium persulfate as an initiator at a temperature of 60 ° C for 24 hours.

The disadvantages of this method include carrying out the process in an acidic medium that inhibits the action of the initiator, the resulting copolymers can lose solubility as a result of a high degree of grafting at amino groups, which complicates further processing of the copolymer into products, the impossibility of determining the physicochemical characteristics of the grafted block.

A known method of obtaining a graft copolymer of chitosan and polymethyl methacrylate in two stages [Synthesis and characterization of chitosan-g-glycidyl methacrylate with methyl methacrylate / E.A. Elizalde-Pena, N. Flores-Ramirez, G. Luna-Barcenas, S.R. Vasquez-Garcia, G. Arambula-Villa, B. Garcia-Gaitan, J.G. Rutiaga-Quinones, J. Gonzalez-Hernandez // European Polymer Journal. - 2007. - Vol.43. - Is. 9. - P. 3963-3969]. At the first stage, chitosan is functionalized with glycidyl methacrylate in a 0.4 M aqueous solution of acetic acid with the addition of 0.05 M KOH solution to maintain the pH of the reaction mixture at 3.8. The process takes 2 hours at 60 ° C. In the second stage, methyl methacrylate is copolymerized with the product obtained in the first stage. A mixture of 0.4 M acetic acid and tetrahydrofuran in a ratio of 7: 3 is used as a solvent; azobisisobutyronitrile acts as an initiator at 70 ° C for 3 hours.

The disadvantages of this method include the occurrence at the first stage of the side reaction of glycidyl methacrylate polymerization, the need to control the pH environment, low yield of the target product, the impossibility of determining the physicochemical characteristics grafted to the main chain of chitosan polymethymethacrylate fragments.

There is a known method for copolymerizing chitosan with synthetic polymers (monomers) (Patent RU No. 2292354, IPC С08В 37/06, С08F 251/02, 27.01.2007) containing functional groups capable of reacting with functional groups of chitosan under the action of shear deformations in the solid phase in as a result of reactive extrusion at temperatures from 20-200 ° C for 5-20 minutes.

The disadvantage of this method is the need to use technically complex equipment - an extruder or a screw-type mechanical reactor.

The known method of heterogeneous graft copolymerization of acrylic acid and chitosan, which is a preformed porous material [A pH-sensitive porous chitosan membrane prepared via surface grafting copolymerization in supercritical carbon dioxide / LQ. Cao, XH. Wang, G. Wang, JD. Wang // Polymer International. - 2015. - Vol. 64 - Is. 3. - P. 383-388]. Graft copolymerization is carried out in a supercritical carbon dioxide medium in the presence of benzoyl peroxide as an initiator at a reaction temperature of 80 ° C and a pressure of 18 MPa for 8 hours.

The disadvantages of this method are the inability to characterize the physicochemical parameters of the grafted polyacrylic blocks, the energy consumption of the process due to the need to maintain the required copolymerization conditions, while the process must be carried out using specific equipment - a reactor capable of withstanding high pressure.

The closest is a method for producing hybrid polymeric materials based on chitosan and synthetic polymers containing oxirane fragments (Patent US6517933, IPC B32B 7/02, C08H 5/04, 2003). The method consists in the formation of a grafted polymer coating on chitosan in the presence of azobisisobutyronitrile, at a temperature of 5-250 ° C, at a mass ratio of chitosan: polymer equal to 95-5: 5-95.

The disadvantage of this method is the need to select suitable solvents for both blocks when using hydrophobic, acetic acid-insoluble synthetic polymers to ensure the homogeneity of the reaction. The loss of solubility of the obtained copolymers upon cooling the mixtures makes it impossible to mortar molding of articles from the obtained modified chitosan. At the same time, there are no data indicating the covalent interaction of chitosan macromolecules and synthetic blocks.

The objective of the present invention is to develop a method for heterophase production of graft copolymers of chitosan, excluding the negative effect of grafting on the ability of chitosan to form products from solutions, due to the loss of solubility.

The technical result is to increase the hydrophobicity of materials based on chitosan while maintaining their biodegradability and biocompatibility.

The technical result is achieved by implementing a method for modifying chitosan, which consists in the synthesis of a copolymer containing oxirane fragments in the presence of azobisisobutyronitrile and grafting the copolymer to chitosan, while grafting the copolymer is carried out by keeping chitosan in the form of chitosan films or a spongy material previously obtained in solutions of 20 ° acetic acid With for 30 minutes in a 1.5-7.5 wt.% Solution of a previously obtained copolymer of glycidyl methacrylate and selected from the series of hexyl methacrylate, n-decyl methacrylate, lauryl methacrylate, tetradecyl methacrylate, stearyl methacrylate derivative of methacrylate in methyl ethyl ketone, taken in monomer molar ratio 1, followed by thermostating the modified chitosan at 140 ° C for 1 hour and washing off the unreacted copolymer by extraction in a Soxhlet apparatus using methyl ethyl ketone as an extractant for 4 hours.

The essence of the invention lies in the modification of chitosan by grafting the obtained copolymer thereto. Grafting is carried out due to the formation of chemical bonds between the corresponding functional groups of the copolymer and chitosan: as a result of the interaction of oxirane rings in the structure of the glycidyl methacrylate units of the modifying copolymer with the hydroxyl and amine groups of chitosan. The method is carried out heterophase and includes the treatment of chitosan with a 1.5-7.5% (wt.) Solution of the copolymer in methyl ethyl ketone for 30 minutes, followed by heat treatment at 140 ° C.

For the synthesis of the copolymer, glycidyl methacrylate is used as one of the monomers, and an alkyl derivative of methacrylate selected from the series of hexyl methacrylate, n-decyl methacrylate, lauryl methacrylate, tetradecyl methacrylate, stearyl methacrylate, in a molar ratio of 4, is used as the second monomer, in the molar ratio of the first, and the ratio of the first is 1 and 1.

The advantages of the claimed method for modifying chitosan include the possibility of grafting polymers to the chitosan chain, the interaction of which with chitosan in solution is hindered by the absence of solvents miscible with an aqueous solution of acetic acid in a wide range of concentrations (i.e., the possibility of heterophase modification). The technological design of the process does not require the use of a complex hardware base.

Grafting onto the surface of chitosan films of copolymers of glycidyl methacrylate and alkyl methacrylates (molar ratio of comonomers 4: 1) using 1.5-7.5% (wt.) Modifying solutions makes it possible to impart hydrophobicity, characterized by contact angles up to 100 degrees. In the case of aerogels (spongy materials), treatment with copolymers of glycidyl methacrylate and alkyl methacrylates makes it possible to achieve a superhydrophobic state with a contact angle of ~ 150 degrees.

The values of the contact angles of the modified chitosan films and aerogels are given in Tables 1 and 2.

Table 1 Modifier Contact angle, ° Concentration of the modifying copolymer solution,% wt. 1.5 3 4.5 6 7.5 Chitosan film without modifier 93 copolymer 1 95 88 copolymer 2 98 98 copolymer 3 99 copolymer 4 97 98 copolymer 5 100 100 100

table 2 Modifier Contact angle, ° Concentration of the modifying copolymer solution,% wt. 1.5 3 4.5 6 7.5 Chitosan airgel without modifier 123, the drop is quickly absorbed copolymer 1 139 139 copolymer 2 151 copolymer 3 141 copolymer 4 142 142 copolymer 5 150 150

FIG. 1 shows a scheme for grafting a copolymer to a chitosan film or sponge material (airgel).

FIG. 2 shows images from a scanning electron microscope (with a magnification of x165) of airgel chips before (1) and after (2) modification, for example, a 3% (wt.) Solution of copolymer 3 in methyl ethyl ketone. The obtained chitosan aerogels have high porosity, the pore sizes are 100-200 microns. The pore walls are film formations with a thickness of 600-700 nm.

FIG. 3 shows the IR spectra of the samples before (1) and after (2) modification, for example, a 3% (wt.) Solution of copolymer 3 in methyl ethyl ketone after extraction by the presence of a peak at 1728 cm ^-1 corresponding to stretching vibrations of the carbonyl group in esters, confirming the formation of a graft copolymer of chitosan.

The invention is illustrated by the following examples.

Example 1. Obtaining chitosan films

To obtain chitosan films, a solution of chitosan in acetic acid is prepared as follows: 2 g of chitosan is placed in a glass with a capacity of 200 ml, 96 g of water is added and stirred for 30 minutes, after which 2 g of acetic acid is added dropwise, stirring is continued for 3 hours, after whereby the solution is filtered under vacuum through a Schott filter to separate undissolved particles. 10 g of chitosan solution are placed in polystyrene Petri dishes 10 cm in diameter and dried to constant weight at 40 ° C. The resulting films are reduced from a water-soluble form to an acid-soluble form by keeping in a water-alcohol solution of ammonia (13% (wt.) Ammonia solution in a mixture of water and methanol = 1: 1 vol) for 30 minutes, followed by repeated washing with distilled water to a neutral medium and drying to constant weight at 40 ° C.

Example 2. Obtaining spongy chitosan materials (aerogels)

Analogously to example 1, a 1% (wt.) Solution of chitosan in 1% (wt.) Aqueous acetic acid was prepared, after which a 3% (wt.) Aqueous solution of glutaraldehyde was added (the molar ratio of glutaraldehyde: chitosan was 1: 1). The reaction mixture was stirred for 30 minutes on a magnetic stirrer. The resulting gel was degassed in an ultrasonic bath for 10 minutes, 75 g of chitosan solution was placed in polystyrene Petri dishes 10 cm in diameter and left for 72 hours at room temperature. Next, the hydrogel was frozen for 12 hours at -30 ° C, followed by defrosting for 6 hours at 25 ° C. The gel was transferred from the salt form to the basic form with an aqueous-alcoholic solution of ammonia (13% (wt.) Ammonia solution in a mixture of water and methyl alcohol = 1: 1 parts by volume) within 24 hours. Further washing to a neutral medium was carried out with distilled water. The reduced hydrogels were frozen at -30 ° C and then dried at -82 ± 2 ° C under vacuum in a freeze dryer.

Example 3. Synthesis of copolymers

For the synthesis of a copolymer of glycidyl methacrylate and an alkyl derivative of methacrylate, selected from the series of hexyl methacrylate, n-decyl methacrylate, lauryl methacrylate, tetradecyl methacrylate, stearyl methacrylate, in a molar ratio of monomers 4: 1, 0.05 g isobutyron azobutyryl initiator is placed in a 20 ml flask with a volume of 20 ml; , the first monomer is glycidyl methacrylate (1.7059 g, 12.0 mmol), the second monomer selected from the claimed series (3 mmol). Methyl ethyl ketone is added so that with a total comonomer concentration in the mixture of 1.5 mol / L, the total volume of the mixture is 10 ml. The mixture is bubbled with an inert gas (dried nitrogen or argon) for 20 minutes to remove air and stir the components, and then thermostatted at 70 ° C for 24 hours. The polymer is precipitated into ice-cold methanol (-20 ° C), separated by decantation and dried under reduced pressure for 24 hours.

In accordance with example 3, the following copolymers were obtained:

copolymer 1 - copolymer of glycidyl methacrylate and hexyl methacrylate;

copolymer 2 is a copolymer of glycidyl methacrylate and n-decyl methacrylate;

copolymer 3 is a copolymer of glycidyl methacrylate and lauryl methacrylate;

copolymer 4 is a copolymer of glycidyl methacrylate and tetradecyl methacrylate;

copolymer 5 is a copolymer of glycidyl methacrylate and stearyl methacrylate.

Example 4. Preparation of copolymer solutions

To prepare a 1.5% (wt.) Solution of the obtained copolymer in methyl ethyl ketone, a sample of the copolymer weighing 0.3 g is dissolved in 19.7 g of methyl ethyl ketone.

To prepare a 3% (wt.) Solution of the obtained copolymer in methyl ethyl ketone, a weighed portion of the copolymer weighing 0.6 g is dissolved in 19.4 g of methyl ethyl ketone.

To prepare a 4.5% (wt.) Solution of the obtained copolymer in methyl ethyl ketone, a weighed portion of the copolymer weighing 0.9 g is dissolved in 19.1 g of methyl ethyl ketone.

To prepare a 6% (wt.) Solution of the obtained copolymer in methyl ethyl ketone, a sample of the copolymer weighing 1.2 g is dissolved in 18.8 g of methyl ethyl ketone.

To prepare a 7.5% (wt.) Solution of the obtained copolymer in methyl ethyl ketone, a sample of the copolymer weighing 1.5 g is dissolved in 18.5 g of methyl ethyl ketone.

Example 5. Modification of chitosan

Chitosan in the form of a film or spongy material is immersed in a solution of a previously obtained copolymer of glycidyl methacrylate and an alkyl derivative of methacrylate in methyl ethyl ketone, kept at 20 ° C in solution for 30 minutes, removed from the solution and thermostated at 140 ° C for 1 hour. After thermostating, the sample is washed from the unreacted copolymer by extraction in a Soxhlet apparatus using methyl ethyl ketone as an extractant for 4 hours.

Thus, a method for modifying chitosan, which consists in the synthesis of a copolymer containing oxirane fragments in the presence of azobisisobutyronitrile and grafting of the copolymer to chitosan by keeping the chitosan at 20 ° C for 30 minutes in a 1.5-7.5% (wt.) Solution of a previously prepared copolymer of glycidyl methacrylate and selected from a number of hexyl methacrylate, n-decyl methacrylate, lauryl methacrylate, tetradecyl methacrylate, stearyl methacrylate derivative of methacrylate in methyl ethyl ketone, taken in a molar ratio of monomers equal to 4: 1, followed by thermostating the modified chitosan at 140 ° C, provides an increase in the hydrophobicity for 1 hour for 1 hour chitosan while maintaining their biodegradability and biocompatibility.

Claims (1)

A method for modifying chitosan, which consists in the synthesis of a copolymer containing oxirane fragments in the presence of azobisisobutyronitrile and grafting of the copolymer to chitosan, characterized in that the grafting of the copolymer is carried out by keeping chitosan in the form of chitosan films or a spongy material previously obtained in acetic acid solutions at 20 ° C 30 minutes in a 1.5-7.5 wt.% Solution of a previously obtained copolymer of glycidyl methacrylate and selected from the series of hexyl methacrylate, n-decyl methacrylate, lauryl methacrylate, tetradecyl methacrylate, stearyl methacrylate derivative of methacrylate in methyl ethyl ketone, taken in a molar ratio of 4: 1 monomer subsequent thermostating of the modified chitosan at 140 ° C for 1 hour and washing from the unreacted copolymer by extraction in a Soxhlet apparatus using methyl ethyl ketone as an extractant for 4 hours.

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