WO1991000298A1

WO1991000298A1 - Method for continuous manufacture of microcrystalline chitosan

Info

Publication number: WO1991000298A1
Application number: PCT/FI1990/000173
Authority: WO
Inventors: Henryk Struszczyk; Antoni Niekraszewicz; Krzystyna WRZES^´NIEWSKA-TOSIK; Stanislaw Koch; Olli KIVEKÄS
Original assignee: FIREXTRA Oy; Instytut Wlokien Chemicznych
Current assignee: FIREXTRA Oy; Instytut Wlokien Chemicznych
Priority date: 1989-06-30
Filing date: 1990-07-02
Publication date: 1991-01-10
Anticipated expiration: 1991-12-30
Also published as: FI83426B; NO910707L; NO303339B1; RU2046800C1; FI83426C; NO910707D0; FI893223L; FI893223A0

Abstract

In a method for continuous manufacture of microcrystalline chitosan by precipitation of chitosan from its aqueous solutions in organic or inorganic acid, or their salts, the chitosan solution in an aqueous acid solution, especially in acetic acid, with polymer concentration not lower than 0.01 wt%, preferably with polymer concentration within 0.1-2.0 wt%, is continuously introduced into a reactor together with an alkaline solution, such as an aqueous solution of an alkaline metal hydroxide or a salt thereof having a concentration ranging from 0.1 to 20.0 wt%. The chitosan solution is introduced into the reactor with a rate within a range of 0.1-20 volume parts per 1 hour and 1 reactor volume part, and the alkaline solution is introduced into a reactor with a rate ranging from 0.1 to 10.0 volume parts per 1 hour and 1 reactor volume part to obtain a mixture pH of equal to or higher than 7. The microcrystalline chitosan dispersion having said pH is simultaneously taken off from the reactor by a continuous system with a rate suitable to keep a constant reaction mixture volume in the reactor, and the microcrystalline chitosan dispersion is collected in a compensation tank and is continuously purified, especially by continuous water washing or by ultrafiltration method. The purified microcrystalline chitosan is finally concentrated to obtain a polymer content of 0.5-10.0 wt% and dried by some well-known method.

Description

Method for continuous manufacture of microcrystalline chitosan

This invention relates to continuous manufacture of microcrystalline chitosan. Up to now there is known a method for manufacture of chitosan by a periodical system, the chitosan so manufactured having developed intrinsic surface. The method is based on periodical precipitation of chitosan with especially a deacetyla- tion degree higher than 30%. The chitosan is dissolved in the aqueous solution of organic or inorganic acid, and it is precipitated by aqueous solutions of alkaline metal hydroxides with application of strong stirring. The precipitated chitosan in a form of gel or disper¬ sion is subjected to a purification process by several water washing. There is also known a method of manufac¬ ture of precipitated chitosan in a form of gel or dispersion preceded by a thermal degradation process realized by organic or inorganic acid treatments in a temperature not lower than 50°C and in a time not shorter than 1 hour. The well-known methods permit to obtain chitosan with a yield ranging within 70-90%. The well-known methods are carried out in the reactors having stirrers of having homogenizers. The well- known methods are described in the Polish Patent of 125 995 as well as in "Journal of Applied Polymer ScienceA vol. 33, page 177, 1987.

Periodical system of manufacture of microcrystalline chitosan causes that its production cycle is time- consuming, taking up time not less than 12-24 hours. It also causes high consumption of energy as well as washing water. The microcrystalline chitosan obtained is characterized by heterogenenouε properties in the respective portions. The well-known method does not allow to obtain microcrystalline chitosan with homoge¬ nous properties. The object of this invention is continuous manufac¬ ture of microcrystalline chitosan, by continuous precipitation of microcrystalline chitosan by an aqueous solution of alkaline metal hydroxides from the standard chitosan dissolved in an aqueous organic or inorganic acid, or in a solution of their salts.

In accordance with a preferred embodiment of a method of the invention, the continuous manufacture of micro- crystalline chitosan by initiation of chitosan precipi¬ tation from its aqueous solution in the organic or inorganic acids or their salts, by an aqueous solution of alkaline metal hydroxides or their salts, comprises that a chitosan solution in the an aqueous acid solution, especially acetic acid with polymer con¬ centration not lower than 0.01 wt%, is introduced by a continuous system to a reactor, together with an aqueous solution of an alkaline metal hydroxides or a salt thereof, especially with an aqueous sodium hydroxide solution with a concentration of 0.1-20 wt%. At the same time the chitosan solution is introduced into a reactor with a rate of 0.1-20 volume parts per 1 hour and per 1 volume part of working reactor capacity, whereas the alkaline solution is introduced with a rate of 0.1-10 volume parts per 1 hour and per 1 volume part of working reactor capacity. The reagent introduced into a reactor with the above rate assures the maintenance of the pH of the reaction mixture on a level equal to or higher than 7. At the same time from a reactor microcrystalline chitosan dispersion with a pH equal to or higher than 7 is withdrawn by the continuous system with a rate necessary to maintain a constant volume of the reaction mixture. Next the microcrystalline chitosan dispersion is storaged into a container and then it is purified by the continuous water washing or by the ultrafiltration technique, the purification being continued to a moment where the conductivity of the effluent is equal to the con- ducivity of the water used. Purified microcrystalline chitosan dispersion is subjected to eventual concentra¬ tion to the polymer content of 0.5-10.0 wt% and drying by the well-known methods.

According to a preferred embodiment of the invention, the continuous manufacture of microcrystalline chitosan comprises also that a chitosan solution in aqueous solutions of acids, and the aqueous solutions of alkaline metal hydroxides as well as their salts are introduced continuously with a rate described above into a reactor equipped with a system of continuous circulation and the product is circulated in a closed reactor system, and at the same time a stream of microcrystalline chitosan is continuously withdrawn. The stream is divided in two parts . The first part is returned into the reactor and the second part is directed to a compensation tank and then it is puri- fied. The microcrystalline chitosan dispersion is taken off from the reactor with a rate suitable to keep a constant volume of reaction mixture in the reactor. The application of an additional circulation allows to obtain microcrystalline chitosan with a high degree of properties of homogeneity. In the aim of further enlargement of the degree of homogeneity of the content as well as improvement of the properties of microcrys¬ talline chitosan, an aqueous solution of alkaline metal hydroxide is introduced directly into the circulation system of the reactor.

The method according to the invention allows to obtain a microcrystalline chitosan in a form of dispersion characterized by properties suitable for colloids and distinguished by the water retention value of WRV up to 5000%, particles dimension ranging from 0.1 to 50μm as well as dispersion form stability. A dried product is characterized by a powder form with a particles dimension within l-100μm and it is distinguished by WRV of 200-600%, crystallinity index Krl up to 95% and a minimal dispersion of chitosan parameters. The method according to the invention allows to obtain a high yield of products on a level of 95-99% in relation to the amount of standard chitosan used, and at the same time the method assures the reduction of raw materials and energy consumption as well as the reduction of manufacturing costs, and also the elimina- tion of arduous operation, in comparison to a periodi¬ cal process. An important object of method according to the invention is to reduce time for microcrystalline chitosan manufacture in .comparison to a periodical method. The investigations have shown that a microcrys- talline chitosan obtained according to the method of the invention in a time of 1-5 hours is related to an amount of product produced in a time of 12-24 hours according to a periodical method. Another important object of the method according to the invention is to assure the continuous precipitation of microcrystalline chitosan with required particles dimensions as well as properties, regulated by the concentration, the introduction rate of the reagents and also eventually by dispersion circulation rate in a reactor. A method according to the invention allows to manufacture homogenous products with reproducible parameters in a time of production without outside intervention which has required time in the periodical method.

Microcrystalline chitosan obtained by the method according to the invention is applied to the polymeric films formation in the chemical industry, medicine, pharmaceutical as well as cosmetic industries and also in agriculture.

Amethod for continuous manufacture of microcrystalline chitosan according to the invention is realized by an installation, which as an example is presented on the appended schematic figure.

The installation for microcrystalline chitosan anufac- ture is equipped with a reactor !_ containing a stirrer 2. In the upper part of the reactor vessel there is a pipe- 3 for introduction of chitosan solution and a pipe 4 for introduction of the precipitating agent, such as hydroxide solution. A pipe 5 for microcrystal- line chitosan dispersion drained off from the reactor 1 is equipped with a pump 6, whose exit is joined to a circulation system 7 for continuous returning of part of dispersion into -the reactor 1 and secondly the exit is joined to a pipe 8 for the dispersion conveyed into a compensation tank 9. The pipe 5 is located in a lower part of the reactor 1. The compensa¬ tion tank 9 is joined to an installation 10 for continuous purification of microcrystalline chitosan dispersion, which is equipped with pipes 11 for introduction and draining of purification water as well as with a pipe 12 for the draining of the purified product. The installation 10 can have also the form of a ultrafiltration system. Additionally, the circula¬ tion system 7 of the reactor 1 is equipped in its upper part with a pipe 13 for introduction of the precipitating agent, such as hydroxide solution.

The action of the installation is the following: The initiation of the precipitation process after the raw materials introduction into the reactor 1 with the working stirrer 2 is performed such that the raw materials are continuously introduced into the reac¬ tor 1. A hydroxide solution is introduced into the reactor 1 by the pipe 4, or by the pipe 13 into the circulation system 7, in dependence of the chosen system. The neutralization of the reaction mixture up to the value of pH equal to or higher than 7 takes place in the reactor 1 with continuous stirring and optional dispersion circulation. The microcrystalline chitosan dispersion obtained is simultaneously taken off from the reactor 1 by a continuous system by the pipe 5 and it is completely conveyed into the compensa- tion tank 9, or it is divided in two parts whereof the first is conveyed into the compensation tank 9 and the second part is introduced into the circulation system 7 • and returned into back into the reactor 1. The microcrystalline chitosan present in the compensation tank 9 is next delivered into the purification instal¬ lation 10. The microcrystalline chitosan is delivered after purification to a storage installation or to a dryer.

The invention is explained further in the following examples which do not restrict the scope of claims.

Example 1.

500 volume parts of 1% chitosan solution in a 4% aqueous solution of acetic acid and 2.5% aqueous sodium hydroxide solution are introduced into a reactor of the type presented on the Figure having the working volume of 1000 volume parts. The chitosan used in the reaction was characterized by average molecular weight of 6.07x10^, deacetylation degree of 71.8% and WRV of 129%. The dispersion of microcrystalline chitosan was precipitated with the working stirrer to obtain a pH of 8.0 and then, by a continuous system, a 1% chitosan solution in 4% aqueous acid solution with an introduction rate of 2400 volume parts per 1 hour and a 4% aqueous hydroxide solution with an introduction rate of 1728 volume parts per 1 hour were introduced to obtain a mixture pH of 8.0 + 0.3. At the same time, microcrystalline chitosan disper¬ sion was taken off from the reactor with a rate suitable to keep a constant volume of mixture in the reactor. Then the dispersion was delivered into a compensation tank and it was next continuously deliver¬ ed into a purification installation, where it was continuously washed by water to obtain a product with an EMP value of 28mV (electromotive power), whereas the initial product was characterized by the EMP value of 95 mV. The product was obtained in a form of stable gel with a white colour and it was charac¬ terized by a microcrystalline chitosan content of 2.45 wt% calculatied on a dry polymer weight, WRV of 906% and an average molecular weight of 3.59x10^. The product yield was 30.9 weight parts of microcrys¬ talline polymer per 1000 volume parts of reactor and 1 hour.

Example 2.

400 volume parts of 1.0% solution of chitosan with the properties shown in Example 1 in a 4% aqueous actic acid solution were introduced into the reactor as in Example 1. The microcrystalline chitosan disper¬ sion was precipitated under continuous stirring with 2.5% aqueous sodium hydroxide solution to obtain a mixture of pH 7.5, whereas 1.0% chitosan solution in a 4% aqueous acetic acid solution with introduction rate of 2940 volume parts per 1 hour and 2,5% aqueous sodium hydroxide solution with a rate of 3060 volume parts per hour were continuously introduced into the reactor to obtain a mixture reaction having a pH of 7.5 ± 0.2. The microcrystalline chitosan formation process was realized with the incorporated circulation system characterized by a rate of circulation of 2940 volume parts per 1 hour. At the same time the preci- pitated microcrystalline chitosan dispersion was taken off for a compensation tank with a rate suitable to keep a constant volume in the reactor. Next the microcrystalline chitosan dispersion with a value of EMP of 112 mV was delivered to a purification installa¬ tion to obtain an eluate with an EMP value of 34 mV.

The product was obtained in a form of stable gel with a white colour and yield of 30.9 weight parts of microcrystalline chitosan per 1 hour and 1000 volume parts of reactor. The product was characterized by 4.8 wt% of microcrystalline chitosan calculated on a dry weight of polymer, and WRV of 3993%.

Example 3.

The microcrystalline chitosan dispersion was made in the reactor as in Example 1 with the application of an 1% chitosan solution in a 4% aqueous acetic acid solution with an introduction rate of 3780 volume parts per 1 hour and with the application of 4% aqueous sodium hydroxide solution with the rate of 3960 volume parts per hour, maintaining other conditions as in Example 1.

The product was obtained in a form of stable gel with a white colour, characterized by microcrystalline chitosan content of 7.44 wt% calculated on a polymer weight, and WRV of 1459%. The yield of product was 36 weight .parts of polymer from 1000 reactor volume parts and 1 hour.

Example 4.

400 volume parts of 0.5% chitosan solution in 4% aqueous acetic acid solution characterized by proper- ties as in Example 1 was introduced into the reactor as in Example 1. The microcrystalline chitosan disper¬ sion was precipitated during a continuous stirring by 2.5% aqueous sodium hydroxide solution to obtain a pH of 7.8. A 0.5.% chitosan solution in 4% aqueous acetic acid solution with a constant rate of introduction of 5280 volume parts per 1 hour, and 2.5% aqueous sodium hydroxide solution with an introduction rate of 5900 volume parts per 1 hour were continuously introduced to obtain a mixture pH of 7.7+0.3. Production and purification process were the same as in Example 1.

The product was obtained in a form of stable gel with white colour, characterized by microcrystalline chitosan content of 6.5 wt% calculated on a dry polymer weight, and WRV of 1994%. The reaction yield was 26.4 weight parts of microcrystalline polymer per 1000 reactor volume parts and 1 hour.

Example 5.

400 volume parts of 0.5% chitosan solution in 2% aqueous acetic acid solution characterized by proper¬ ties as in Example 1 was introduced into the reactor as in Example 1. The microcrystalline chitosan disper¬ sion was precipitated with a continuous stirring using a 2.5% aqueous sodium hydroxide solution to obtain a mixture pH of 7.4, and a 0.5% chitosan solution in a 2% aqueous acetic acid solution was continously introduced with the sodium hydroxide solution rate as in Example 4 to obtain a mixture pH of 7.4_,+0.1 Production and purification processes were the same as in Example 1. The initial microcrystalline chitosan dispersion was characterized by the value of EMP of 85 mV and after purification process the value of EMP of was 15 V.

The product was obtained in a form of stable white gel characterized by microcrystalline chitosan content of 9.25 wt% calculated on a dry polymer weight and WRV of 850%. The product yield was 15.7 weight parts of microcrystalline polymer per 100 reactor volume parts and 1 hour.

Example 6.

The microcrystalline chitosan dispersion was obtained in a reactor as in Example 1 using 1% chitosan solution in a 4% aqueous acetic acid solution, as well as a 7.5% aqueous sodium hydroxide solution introduced into a working circulation system. Then 1% chitosan solution in a 4% aqueous acetic acid solution with a constant introduction rate of 5280.volume parts per 1 hour, as well as a 7.5% aqueous sodium hydroxide solution with an introduction rate of 1944 volume parts per 1 hour were continuously introduced into the reaction mixture having the initial pH of 7.8, to obtain a mixture pH of 7.7+0.2. Production and purification processes were analogous to those in Example 1. The initial dispersion produced was characterized by EMP value of 99 mV and after purification the EMP was 29 mV.

The product was obtained in a form of stable white gel characterized by microcrystalline chitosan content of 9.05 wt%, calculated on a dry polymer weight, WRV of 587% and average molecular weight of 3.62x10^. The product yield was 36 weight parts of microcrystal¬ line polymer per 1000 reactor volume parts and 1 hour.

Example 7.

500 volume parts of 0.5% chitosan solution in a 4% aqueous acetic acid solution was introduced into the reactor as in Example 1. The chitosan used was charac¬ terized by average molecular weight of 7.7x10^, deacetylation degree of 67.5% and WRV of 230%. The microcrystalline chitosan dispersion was precipitated with stirring the 0.5% chitosan solution in the 4 % aqueous acetic acid to obtain a pH of 7.9, and then with a continuous method using the continuous circula¬ tion system as in Example 2. A 0.5% chitosan solution in 4% aqueous acetic acid solution with a constant introduction rate of 5280 volume parts per 1 hour, as well as 5.0% aqueous sodium hydroxide solution with a constant introduction rate of 2880 volume parts per 1 hour were introduced into the reactor, thus obtaining a mixture pH of 7.7.+.0.3. Production process was realized as in Example 2, whereas the purification process was realized in a ultrafiltration installation to obtain an EMP value of 9 mV.

The product was obtained in a form of stable white gel characterized by microcrystalline chitosan content of 9.05 wt%, calculated on a dry polymer weight, WRV of 830% and average molecular weight of 4.9.10⁵. The product yield was 36 weight parts of microcrystalline polymer per 1000 reactor volume parts and 1 hour.

Example 8.

500 volume parts of 0.75 wt% chitosan solution in a 1.5 wt% aqueous acetic acid solution characterized by

^• properties as in Example 7 was introduced into a reactor as in Example 1. The microcrystalline chitosan dispersion was precipitated with a continuous stirring using a 5.5 wt% aqueous sodium carbonate solution to obtain a mixture with a pH of 7.6, whereafter 0.75 wt% chitosan solution in a 1.5 wt% aqueous acetic acid solution was continuously introduced with constant rate of 6250 volume parts per 1 hour, and a 5.5 wt% aqueous sodium carbonate solution at a rate of 9500 volume parts per 1 hour was introduced to obtain a mixture pH of 7.6±0.1. Production and purification procedure was the same as in Example 7. The initial microcrystalline chitosan dispersion was characterized by the value of EMP of 70 mV and after purification of the EMP was 8 mV.

The product was obtained in a form of stable white gel characterized by microcrystalline chitosan content of 4.5 wt% calculated on a dry polymer weight, and WRV of 1450%. The product yield was 19.8 weight parts of microcrystalline polymer per 1000 reactor volume parts and 1 hour.

Claims

Claims :

1. Method for continuous manufacture of icrocrystal-^' line chitosan by precipitation of chitosan from its aqueous solutions in organic or inorganic acid, or their salts, using aqueous solutions of alkaline hydroxides or their salts, characterized in that the chitosan solution in an aqueous acid solution, especially in acetic acid, with polymer concentration not lower than 0.01 wt%, preferably with polymer con¬ centration within 0.1.-2.0 wt%, is continuously intro¬ duced into a reactor together with an alkaline solu¬ tion, such as an aqueous solution of an alkaline metal hydroxide or a salt thereof having a concentra¬ tion ranging from 0.1 to 20.0 wt%, whereas the chitosan solution is introduced into the reactor with a rate within a range of 0.1-20 volume parts per 1 hour and 1 reactor volume parts, and the alkaline solution is introduced into a reactor with a rate ranging from 0.1 to 10.0 volume parts per 1 hour and 1 reactor volume part to obtain a mixture pH of equal to or higher than 7, whereas at the same time the microcrys¬ talline chitosan dispersion having said pH is taken off from the reactor by a continuous system with a rate suitable to keep a constant reaction mixture volume in the reactor, and the microcrystalline chitosan dispersion is collected in a compensation tank and is continuously purified, especially by continuous water washing or by ultrafiltration method, and then the purified microcrystalline chitosan is concentrated to obtain a polymer content of 0.5-10.0 wt% and dried by some well-known method.

2. A method as claimed in claim 1, characterized in that the microcrystalline chitosan dispersion manufactured in the reactor is subjected to continuous circulation in a closed reactor system, whereas at the same time a microcrystalline chitosan dispersion is carried away from the reactor by the continuous system with a rate necessary to keep a constant reaction mixture volume, and the microcrystalline chitosan dispersion is subjected to a purfication process.

3. A method as claimed in the claim 2, charac¬ terized in that the alkaline solution is introduced directly to the circulation system containing the microcrystalline chitosan dispersion.

4. A method as claimed in the claims 1 and 2, characterized in that the microcrystalline chitosan purification is realized to obtain an effluent conduc¬ tivity equal to the conductivity of water used.