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DESCRIPTION RU2330670

METHOD OF OBTAINING CHITOSAN

The present invention relates to pharmacology and allows you to get the natural compound
chitosan, widely used in pharmacology.

A method of producing chitosan is known, including one-time deproteinization with 3.5% sodium
hydroxide solution for 2 hours at t = 65 ° C, filtering the suspension, washing the solid phase,
demineralization (decalcification) with 3.65% HCl solution for 30 minutes at room temperature,
filtration, washing, extraction with acetone, drying, bleaching with a 0.315% sodium hypochlorite
solution, washing and drying the chitin obtained, deacetylation with 50% sodium hydroxide
solution at 100 ° C for 30 minutes, washing and drying the obtained chitosis ana (Meyers S.P., No.
N.K., Lee K.S. Isolation and characterization of chitin from crabfish shell waste J. Agric. Food
Chem. 1989, 37, 575).

The disadvantages of this method are a large number of manual operations, because the process
is decorated according to a periodic method; the inability to remove most of the proteins and
calcium hydroxide due to the too short time of the process of deproteinization and decalcification;
completely insufficient time for the stage of deacetylation; excessive phase of extraction, and,
moreover, flammable and explosive and toxic reagent - acetone; whitening the finished chitin with
sodium hypochlorite, the active chlorine of which to some extent destroys the chitin molecule; the
appearance of active chlorine in wastewater after long-term washing of chitin to the complete
absence of chlorine in the product. The result is chitosan with a degree of deacetylation not higher
than 60-70%, with a high content of proteins and mineral impurities, as well as with a low viscosity.

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The closest analogue of the proposed invention is a method for producing chitosan, including
grinding natural chitin-containing raw materials to particles with a size of 100-200 microns;
extraction of powder with liquid carbon dioxide for 1-3 hours; the first decalcification of the powder
with a 5-10 fold excess of 0.8-2.5% hydrochloric acid at 35-50 ° C for 0.5-2 hours; washing the
solid with water at 50-75 ° C to pH 5.4; conducting the 1st deproteinization at 4-7-fold volume of
water and pH 9.0-10.5 by adding solid sodium hydroxide to water. In the resulting suspension add
the enzyme in an amount of 0.1-0.5% by weight of dry powder; drain the liquid phase; wash the
residue with water; the second decalcification is carried out in 5-7-fold by weight of dry powder in
an amount of 0.8-2.5% hydrochloric acid at a temperature of 35-50 ° C for 0.5-2 hours; washed the
reaction mass; 4-7-fold volume of water is added and its pH is adjusted to 9.0-10.5 by adding solid
sodium hydroxide and 0.1-0.5% by weight of the dry powder enzyme.

Deproteinization takes 2-4 hours at a temperature of 50-70 ° C; the mother liquor is drained, 2-4
volumes by weight of dry chitin are added, 45-50% sodium hydroxide and deacetylation is carried
out at a temperature of 85-95 ° C for 2-4 hours; washed with chitosan water at a temperature of
60-80 ° C to a pH of 6.5-7.4; chitosan centrifuged; dried and crushed (US Pat. Of the Russian
Federation No. 2221811).

The disadvantages of this method are:

a large number of operations (8) in the production of the product, performed manually, because
process is decorated as a periodic;

an excessively high degree of grinding of the raw material, as a result of which the loss of the
processed material will be large and will increase as the proteins (up to 40%) and CaCO3 are
removed (up to 30%) from the raw material and the associated further reduction in the size of
grains;

dangerous operation of extraction of powder with liquid carbon dioxide, which retains a liquid state
only under pressure above 60 kgf / cm2. The operation is only possible in the autoclave and
becomes under the supervision of the Gosgortekhnadzor;

difficulties in the resuspension of powder precipitate deposited on the bottom of industrial reactors

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after removal of the mother liquors and the likely breakdown of the gearbox when the engines of
the agitators are turned on;

the need for devices to ensure the safe release of CO2 pressure from the reactor;

the temperature of the decalcification process is too high and

associated with this increased destruction of the chitin molecule;

the hydrogen chloride contained in the hydrochloric acid introduced for decalcification is not
enough to completely remove calcium carbonate;

washing the obtained calcined chitin-protein complex (KHBK) from hydrogen chloride to pH 5.4
requires a large flow of water and is long in time;

the use of drinking water for washing is associated with an increase in the content of hardness
salts (non-combustible residue) in the finished product;

preparation of alkaline solution for deproteinization directly in the reactor by adding solid alkali to
the suspension - hazardous reception, associated with spontaneous rise in temperature and local
overheating at the site of alkali into water;

the temperature, time and duration of deacetylation are insufficient to achieve a high degree of
deacetylation.

In order to obtain high-quality chitosan, suitable for use in medicine, as well as to avoid the above-
mentioned disadvantages of the known method, the following method of obtaining chitosan is
proposed. the principle of countercurrent, in which the processed material in contact with fresh
reagents as the process progresses. Depending on the quality and composition of the raw
materials (crushed crab shell - hereinafter referred to as “grains of crab”), the number, order and
duration of application of the decalcification and deproteinization stages can be changed. If in the
crab crumbs the fraction fraction minus 3 mm exceeds 3%, the amount and time of decalcification

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and deproteinization is reduced. When the content in the crumbs of CaCO3 crab is more than 40%
or proteins over 45%, the amount and time of deproteinization or decalcification are reduced,
respectively.

As a result, white chitin is obtained, practically free of CaCO3 and with a very small residue of
proteins. Selected chitin is subjected to deacetylation reaction with high-percentage sodium
hydroxide at elevated temperature. All reactions are carried out in a nitrogen atmosphere, in a
chain of standard steel apparatus with a high-quality glass-enamel coating, with a capacity of 6.3-
2.5 m3, equipped with stirrers, thermowells, fittings for entering and removing reactive
components, jackets for heating and cooling the reaction masses, and also in the apparatus of
steel Х18Н10Т, since during deacetylation the glass-enamel coating of the reactors is destroyed
by high temperatures and alkali concentrations.

The loading of components, reagents, removal of mother liquors and wash water is mechanized.
They are carried out due to the vacuum created in each of the devices.

In contrast to the known methods, the proposed solution as an alkaline agent is a liquid solution of
sodium hydroxide obtained by the method of diaphragm electrolysis. Due to the use of caustic
diaphragm soda liquid, the need for hazardous and labor-intensive work on crushing and
dissolving solid alkali was eliminated.

All devices before loading reagents and processed material into them are filled with nitrogen.

The essence of the method is as follows.

th deproteinization. Reactor A-1 is filled with nitrogen and 800 kg of crushed crab shell is loaded
into it. 4,000 liters of a 3% NaOH solution prepared by the method of diaphragm electrolysis are
served here at 60-65 ° C. Withstand the slurry with stirring and t = 60-65 ° C for 3-4 hours. After
10-20 minutes, the sludge is discharged into the collection. The remaining calcined chitin-protein
complex (KHBK) is washed with 2400 liters of water at a temperature of 60-65 ° C, the slurry is
stirred for 30-40 minutes, allowed to stand for 10-20 minutes and the wash water is removed into
the collector. The operation is carried out twice.

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1 decalcification. Reactor A-2 is filled with nitrogen, pulp from A-1 is fed in and stirred for 10
minutes. It is allowed to settle for 10 minutes, water is removed from reactor A-2 and 4000 liters of
5% HCl solution are fed with t = 10-20 ° C. Withstand the slurry with stirring and t = 20-25 ° C 1-
1.5 hours. After 10 minutes of sludge, the mother liquor is removed to the collection. The
remaining KHBK is washed with 2400 liters of water at a temperature of 60-65 ° C, the slurry is
stirred for 30 minutes, allowed to stand for 10 minutes and the wash water is removed into the
collection container. The operation is carried out twice.

- I deproteinization. The reactor A-3 is filled with nitrogen, the pulp from A-2 is fed and stirred for
10 minutes. The mixture is allowed to settle for 10 minutes, water is removed from the A-3 reactor
and 4,000 liters of 4% NaOH solution prepared by the diaphragm electrolysis method are fed. 60 °
C. Withstand the slurry with stirring and t = 55-60 ° C for 4 hours. After 10 minutes of sludge, the
mother liquor is removed to the collection. The remaining KHBK is washed with 2400 liters of
water at a temperature of 60-65 ° C, the slurry is stirred for 30 minutes, allowed to stand for 10
minutes and the wash water is removed into the collection container. The operation is carried out
twice.

2 decalcification. Reactor A-4 is filled with nitrogen, pulp from A-3 is fed and stirred for 10 minutes.
The mixture is allowed to settle for 10 minutes, water is removed from reactor A-4 and 2400 liters
of 4% HCl solution are fed with t = 20-25 ° C. Withstand the slurry with stirring and t = 20-25 ° C
for 2 hours. After 10 minutes of sludge, the mother liquor is removed to the collection. The
remaining KHBK is washed with 2400 liters of water at a temperature of 60-65 ° C, the slurry is
stirred for 30 minutes, allowed to stand for 10 minutes and the wash water is removed into the
collection container. The operation is carried out twice.

- I deproteinization. The reactor A-5 is filled with nitrogen, the pulp from A-4 is fed and stirred for
10 minutes. The mixture is allowed to settle for 10 minutes, water is removed from the A-5 reactor
and 2400 liters of 5% NaOH solution prepared by the diaphragm electrolysis method are fed. 55 °
C. Withstand the slurry with stirring and t = 55-60 ° C for 2 hours. After 10 minutes of sludge, the
mother liquor is removed to the collection. The remaining calcined chitin (CC) is washed with 2000

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liters of water at a temperature of 60-65 ° C, the pulp is stirred for 30 minutes, allowed to stand for
10 minutes and the washing water is removed into the collection. The operation is carried out
twice.

3 decalcification. Reactor A-6 is filled with nitrogen, pulp from A-5 is fed and stirred for 20 minutes.
It is allowed to settle for 10 minutes, water is removed from reactor A-6 and 2400 liters of 3% HCl
solution are fed in with t = 20 ° C. Withstand the slurry with stirring and t = 20 ° C for 2 hours. After
10 minutes of sludge, the mother liquor is removed to the collection. The remaining chitin is
washed with 1600 liters of water at a temperature of 40-45 ° C, the pulp is stirred for 30 minutes,
allowed to stand for 10 minutes, and the washing water is removed into the collector. The
operation is carried out to obtain a pH of 6.0. Chitin is obtained in white, practically does not
contain CaCO3 and proteins.

Deacetylation Reactor A-7 is filled with nitrogen, pulp from A-6 is fed and stirred for 20 minutes.
The mixture is allowed to settle for 10 minutes, water is removed from the A-7 reactor and 2,700
liters of 49-55% NaOH solution prepared by the diaphragm electrolysis method are fed. The
process is carried out at t = 95-105 ° C for 7-9 hours. After the reaction time, the mother liquor is
removed in a separate collection, and the finished chitosan is washed.

Fugovka. Initially, moisture from chitosan is removed in a centrifuge at 1400 rpm for 25-40
minutes.

Drying chitosan. The raw chitosan taken from the centrifuge contains about 60% water. It is dried
in a drum vacuum dryer with a residual pressure of 90-120 mm Hg. Art. and t = 60-65 ° C.

In the proposed method of producing chitosan, the yield of the finished product is 94-95%, and its
quality indicators are expressed in the following figures:

- mass fraction of water%, not more than 6 - dynamic viscosity of 1% of p-ra of chitosan in 1%
solution of 10-1000 acetic acid cP, within a range of - degree of deacetylation of%, not less than
90 - mass fraction of insoluble residue of 1% of p-ra of chitosan 0. 1 in 1% p-re acetic acid%, not
more than - mass fraction of residue after calcination%, not more than 0.1 - protein content%, not
more than 0.15 - heavy metal content (Hg, As, Pb, Sb) ppm, not more than 3 - pH of the aqueous
extract, within 6-7.3 - microflora MAFANM, not more than 1 × 10-3

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Due to the gradual and layer-by-layer processing of the raw material, damage to the chitin
molecule is minimized, almost all impurities are completely removed, since here the counterflow
principle is modeled, in which each of the devices as it moves the processed crumbs from the
device into the device, it is found with fresh reagents.

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