Note : Les descriptions sont présentées dans la langue officielle dans laquelle elles ont été soumises.
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Process for ~reparing_aqueous chitosan solutions and
The invention relates to a novel process for
preparing aqueous solutions and gels of chitosan.
Chitosan is a cationic biopolymer which is built
up of recurring units of 1,4-linked D-glucosamine.
Chitosan is the deacetylation product of chitin which is
widely distributed in natural fauna as the skeletal
substance of he armour and shells of crustaceans,
insects and the like. ~ a natural raw material, which
can be obtained in a simple and enviroNmentally
compatible manner fro~ natural regenerable sources,
chitosan is increasingly of interest in industrial
applications. An essential property of chitosan is the
ability to form viscous aqueous solutions. Such solutions
can have a wide variety of applications in chemistry,
pharmacy, cosmetics and food technology. Examples of
these are, for instance, the use as thickener, gel
former, binder, film for~er and adhesive. Chitosan al50
serveæ as a naturally degradable flocculant for waste-
water purification. In the same application, the ability
to bind heavy metals is aIso useful. As a biocompatible
or bioresorbable polymer, chitosan is of particular
interest in pharma~eutical and medical applications such
as, for example, as a constituent of wound dressings or
of materials for endoprostheses.
~ owever, the specific solubility characteristics
of chitosan place limits on its practlcal use. The only
suitable aqueous solvents for chitosan are monobasic
mineral acids such as hydrochloric acid or aqueous
solutionsiof some organic acids such as, for example,
acetic acid and lactic acid. Chitosan is insoluble in
polybasic inorganic acids such as sulfuric acid and
phosphoric acid, and also in virtually all customary
organic solvents. Chitosan solutions can therefore only
be used where the aqueous-acid solvent is unpro~lemati-
cal. The setting of certain viscosity values is essen-
tially only possible via the concentration of chitosan in
the solution. High-viscosity solutions or gels can only
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be achieved by means of a correspondingly high choice of
the chitosan concentration, which in turn is undesired or
disadvantageous for many applications. It would be
desirable to have high viscosity values at a
comparatively low chitosan concentration.
It has now been found that chitosan can be
dissolved in water without problems in a wide
concentration range if acid chelating agents are added.
Furthermore, it has been found that in such solutions the
10 visc08ity can be drastically increased up to high-
viscosity gels without having to change the original
chitosan concentration, if salts of polyvalent metals and
acids in which chitosan is only moderately soluble or
in~oluble are added to these solutions.
Finally, it has also been found that chitosan and
chelating agents can be recovered in the form of a sàlt~
like adduct from a co~mon aqueous solution by removal of
the water or by precipitation using an organic solvent.
This adduct can be redissolved in water without problems.
The invention accordingly provides a process for
preparing aqueous solutions and gels of chitosan in which
chitosan and an acid chelating agent are dissolved in
water.
The invention further provides a process for
preparing high-viscosity chitosan gels in which salts of
polyvalent metals and acids in which chitosan is only
moderately soluble or insoluble are added to aqueous
solutions containing chitosan and an acid chelating
agent.
The invention finally provides a salt-like adduct
of ~hitosan and chelating agent which can be obtained
from corresponding solutions by removal of water or by
precipitation using an organic solvent.
In the process of the invention, any commercial
chitosan can be used.
The acid chelating agents to be used in the
process of ths invention are known per se, for instance
~rom the field of anal~tical chemistry and, in
particular, from complexometric analysis. Chelating
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agents which are suitable for the purpose of the
invention are all bidentate or polydentate chelating
agents which are able to form stable chelate complexes
with, in particular, polyvalent metal ions. Preference is
5 given to using the readily commercially available com-
plexing agents nitrilotriacetic acid (NTA), ethylene-
diaminetetraacetic acid tEDTA), diethylenetriaminepenta-
acetic acid (DTPA), triethylenetetraminehexaacetic acid
(~T~A) or diam~nocyclohexanetetraacetic acid (DCTA).
~hese can, preferably, ~e used in the form of the free
acids, but also in the form of their (partial) sodium
salts. Partiaular preference is given to EDTA.
It has been found that chitosan together with
such chelating agents ~an be dissolved without p~oblems
in water in a wide concentration range, with the mass
ratio of chitosan to the complexing agent also being
largely unproblematical. ~hus, chitosan and chelating
agents in a mass ratio of from 1:0.3 to 1:5 can be
readily dissolved in water to give solutions having a
total content of from O.l`to 2~% by weight. In the case
of low-molecular-weight chitosan, even higher total
contents, for instance up to about 50% by weight, are
possible. These findings are very surprising, since, on
the one hand, the chelating agents have only a weak acid
character in comparison with the acids or acid solutions
customary as solvents for chitosan and, on the other
hand, these chelating agents have only a low solubility
in water itself. Thus, for example, onl~ 0.5 g~l of EDTA
dissolve in water at 22.5~C; for NTA this figure is
1.28 g~l and for DTPA the figure is 3.5 g/l. It is
assumed that chitosan and chelating agents have a
mutually reinforcing solubility-promoting effect on one
another.
The practical procedure in preparing the solution
is simple. Chitosan and the respective chelating agent
are suspended in water, in the desired ratio and in the
desired amount, as pulverulent solids, preferably with
vigorous stirring, the components gradually dissolving.
Ratio and amount of the solution components are selected
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according to the intended application. The properties of
the solution, in particular the viscosity value, can
easily be determined or, by means of simple preliminary
experiments in accordance with the application, be
5 predetermined.
From the aqueous solutions containing chitosan
and an acid chelating agent, these can be recovered in
the form of a salt-like adduct by removal of water or by
precipitation using an organic solvent. In such adducts,
an ionic interaction be~ween chitosan and complexing
agent, resulting from their respective cationic or
anionic character, can be assumed. The removal of water
is preferably carried out by means of spray drying or
freeze drying, with the adduct being obtained in the form
lS of a fine powder.
The precipitation of the chitosan-chelating agent
adduct from the aqueous solution can easily be achieved
by means of the customary organic solvent6 in which
chitosan i5 typically insoluble. Examples which may be
mentioned are acetone,~methanol, ethanol and isopropanol.
Redissolution of such adducts in water is easily
possible without any reduction of the original
solubility.
Such chitosan-chelating agent adducts are thus
valuable and particularly simple to handle starting
materials for preparing chitosan solutions and gels.
According to a further aspect of the invention,
the abovedescribed chitosan solutions can have their
viscosity drastically increased or be converted into
high-viscosity gels, without additional chitosan having
tlo`be introduced to the solution for this purpose. This
effect can be achieved by adding salts of polyvalent
metaIs and acids in which chitosa~ is only moderately
soluble or insoluble to the aqueous solutions containing
chikosan and an acid chelating agent. Particularly
suitable salts are those of divalent metals and among
these, in particular for the purposes of cosmetic,
pharmaceutical and medical applications of the solutions
or gels, the salts of calcium and magnesium. As acids on
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which these salts are based, mention may be made of, in
particular, carbonic acid, sulfuric acid, phosphoric acid
and oxalic acid.
To effect the viscosity increase or gel
formation, appropriate salts are sLmply stirred into the
chitosan solution, these dissolving more or less quickly.
The amount of salt to ~e added is non-critical within a
wide range and has an upper limit imposed by the specific
solubility thereof in the system. It is advantageous to
use the salt in a weight ratio to the chitosan present in
the solution of from 0.01 1 to 5:1 or in a molar ratio to
the chelating ayent present in the solution of from
0.01:1 to 5:1. The ratio to be selected from case to case
depends on the desired viscosity value, which can be
determined in simple routine experLments. In the course
of the dissolution process, the viscosi~ of the solution
increases continuously. The final viscosities are
typically from 4 to 20 times the initial viscosity.
Depending on the initial visco ity o~ the solution and
the amount of the ~alt added, intermediate-viscosity to
high-viscosity solutions and high-viscosity gels can be
produced. This effect is presumably attributable to the
cations of the salt introduced into the system binding
the chelating agent more strongly, thexeby reducing the
solubilizing effect of the latter on chitosan~and, in
combination with the simultaneously liberated acid,
reducing the solubility of the chitosan.
By means of the present invention there are thus
provided, in a simple manner, chitosan solutions and gels
having tailored viscosity values, in particular ones
aving a~ high viscosity at a comparatively low initial
concentration, for a very wide variety of application
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; Example 1 ~ ;~
100 g o~ chitosan together with 70 g of ~DTA are
~ ~ added~to S 1 of demineralized water while stirring. After
; ~ stirring for 12 hours, a clear viscous solution having a
~ viscosity value of 870 cps is obtained.
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Example 2
In a similar way to Example 1, a solution is
prepared from 100 g of chitosan and 50 g of ~7TA.
Viscosity: ~50 cps.
Example 3
In a similar way to Example 1, a solution is
prepared from 100 g of chitosan and 80 g of DTPA .
ViscosityO 850 cps. ~-~
Example 4
Pulv2rulent calcium carbonate is stirred into the
solutlon of E~ample 1 in a ratio of 0.5 g/100 ml of
solution. The dissolution process proceeds with a small ;~
amount of gas evolution (~2)- ~he solution is then
clear~ The viscosity is 3640 cps.
Example_5
Pulverulent calcium carbonate is stirred into the
solution of Example 1 in a ratio of 1 gJ100 ml of
solution. The solution remains turbid, since not all the
calcium carbonate has yet dissolved. The viscosity is
~0 4700 cps. -
After standing for 3 days at 25C, the solution ; ~
is clear. The viscosity is 15,600 cps. --
Example 6
1 1 of the solution obtained in accordance with
Example 1 i8 spray dried. The product obtained is a fine
powder.
1 g of this powder dissolves, with stirring, in
100 ml of water within 15 minutes leaving no residue and -~
giving a viscous solution.
Example 7
il of the solution obtained in accordance with
Example 1 is freeze dried in a flat layer (1 cm) to a
residual moisture content of 15%. The product obtained is
finely pulverized.
1 g of this powder dissolves, with stirring, in ~-
100 ml of water within 15 minutes leaving no residue and - ~ -
giving a viæcou5 solution.
Example 8 ;
500 ml of acetone are slowly added with vigorous ~;
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stirring to 1 1 of the solution obtained in accordance
with Example 1. The chitosan-EDTA adduct precipitates
quantitatively and settles after the stirrer is turned
off. The product is obtained by separating it off from
5 the solution, washing with acetone and drying. : .
1 g of the pulverized product dissolves, with
stirring, in 100 ml of water within 15 minutes ~eaving no
residue a~d giving a viscou~ nlution.
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