U.S. patent application number 09/863104 was filed with the patent office on 2002-01-10 for process for the preparation of lactic acid by evaporative crystallisation.
Invention is credited to Dubois, Eric, Fouache, Catherine.
Application Number | 20020004610 09/863104 |
Document ID | / |
Family ID | 8850527 |
Filed Date | 2002-01-10 |
United States Patent
Application |
20020004610 |
Kind Code |
A1 |
Dubois, Eric ; et
al. |
January 10, 2002 |
Process for the preparation of lactic acid by evaporative
crystallisation
Abstract
The invention relates to a process for the preparation of high
purity lactic acid from an aqueous solution containing said acid in
the form of salt(s), characterised in that the aqueous solution is
treated with a strong acid in order to liberate lactic acid in the
free form and to produce salts of the corresponding strong acid,
said salts of the strong acid are crystallised by evaporative
crystallisation and lactic acid is recovered in the free form in
solution.
Inventors: |
Dubois, Eric; (Lestrem,
FR) ; Fouache, Catherine; (Sailly/Labourse,
FR) |
Correspondence
Address: |
HENDERSON & STURM LLP
1213 MIDLAND BUILDING
206 SIXTH AVENUE
DES MOINES
IA
50309-4076
US
|
Family ID: |
8850527 |
Appl. No.: |
09/863104 |
Filed: |
May 22, 2001 |
Current U.S.
Class: |
562/589 |
Current CPC
Class: |
C07C 51/02 20130101;
C07C 59/08 20130101; C07C 51/02 20130101 |
Class at
Publication: |
562/589 |
International
Class: |
C07C 059/08 |
Foreign Application Data
Date |
Code |
Application Number |
May 23, 2000 |
FR |
0006586 |
Claims
1. A process for the preparation of high purity lactic acid from an
aqueous solution containing said acid in the form of salt(s),
wherein: the aqueous solution is treated with a strong acid in
order to liberate lactic acid in the free form and to produce
corresponding salts of the strong acid, said salts of the strong
acid are crystallised by evaporative crystallisation, lactic acid
is recovered in the free form in solution.
2. A process according to claim 1, wherein the aqueous solution
containing lactic acid in the form of salt(s) is a fermentation
medium from which its microorganisms have been removed.
3. A process according to claim 2, wherein the fermentation medium
undergoes an electrodialysis step in order to obtain an
electrodialysed aqueous solution from which the nonionic
constituents of the fermentation medium have been removed.
4. A process according to claim 3, wherein the electrodialysed
aqueous solution is concentrated to a dry matter content of at
least 30%.
5. A process according to claim 3, wherein the electrodialysed
aqueous solution is concentrated to a dry matter content in the
range from 30% to 50%.
6. A process according to claim 1, wherein in the strong acid is
98% sulphuric acid.
7. A process according to claim 1, wherein the crystals of salts of
the strong acid are separated from lactic acid in the free form by
a method selected from the group of filtration and centrifugation
methods.
8. A process according to claim 1, wherein the crystals of salts of
the strong acid are separated from lactic acid in the free form by
the centrifugation method.
9. A process according to claim 1, wherein lactic acid is present
in the form of a salt of alkaline earth metal selected from the
group consisting of ammonium, magnesium, calcium, sodium and
potassium.
10. A process according to claim 1, wherein the salt of alkaline
earth metal is ammonium.
11. A process according to claim 1, wherein the salt of alkaline
earth metal is sodium.
Description
[0001] The present invention relates to a particular process for
the preparation of lactic acid from an aqueous solution containing
lactic acid, in the form of salt(s) particularly from a
fermentation medium.
[0002] The present invention also relates to a process for the
preparation of lactic acid, the purity of which is such that it may
be used not only in sectors such as food applications, the chemical
and agrochemical industries, plastics, cosmetics, but above all in
pharmaceutical applications.
[0003] According to the invention, a "high purity lactic acid"
means a grade of lactic acid which satisfies the pharmaceutical
standards of purity (thermal stability test of "The United States
Pharmacopeia") and complies with the standards of the "Food
Chemicals Codex".
[0004] The preparation of an aqueous solution of lactic acid in the
form of salt(s) usually means the fermentation of microorganisms of
the Lactobacillus type (such as L. acidophilus, L. delbrueckii or
L. pentosus), Lactococcus, Enterococcus, Pediococcus, Vagococcus,
Tetragenococcus, Aerococcus, Rhizopus, Bacillus (such as B.
coagulans), Streptococcus, Bifidobacterium . . .
[0005] Indeed, it is known that the growth of most of these lactic
acid-producing microorganisms, and even the viability thereof, is
inhibited by the fall in the pH of the fermentation medium, this
strong acidification of the medium being brought about by the
production of organic acids, including lactic acid itself.
[0006] It is necessary, therefore, to control the pH and it is
generally accepted that this must be kept at a value in the range
from 4 to 7, preferably higher than 4.5, for example, in the range
from 5.5 to 6.5, by adding bases such as alkali metal or alkaline
earth metal hydroxides, carbonates or bicarbonates.
[0007] Lactic acid is therefore present in these fermentation media
in the form of salts (lactates of sodium, potassium, calcium or
ammonium, alone or in mixture, depending on the base selected for
controlling the pH of the fermentation medium).
[0008] Consequently, all the methods for recovering lactic acid
from aqueous solutions containing them, and particularly if this
aqueous solution is composed of a fermentation medium, have to
overcome the same difficulties, i.e. carrying out the separation of
the salt(s) of lactic acid, the microorganisms which produced them
and the impurities of the fermentation medium (unconsumed sugars
and proteins, and inorganic salts of various kinds) and, moreover,
carrying out the conversion of the salts of lactic acid to lactic
acid in the free form, which also then requires the removal of the
corresponding base produced.
[0009] Various methods have been proposed for recovering lactic
acid from an aqueous solution, and particularly from a fermentation
medium.
[0010] All these methods are based on the same principle, i.e.
extraction of the lactic acid as such from the fermentation
medium.
[0011] However, as has been shown before, lactic acid is present in
the form of a salt (lactate).
[0012] If the control of the pH of the fermentation medium is
achieved by carbonates or bicarbonates of calcium, lactic acid in
the free form may be recovered, for example, by acidification of
the medium with sulphuric acid.
[0013] In this case, the reaction gives rise to the formation of
calcium sulphates (gypsum) which precipitate and to the release of
lactic acid in the free form which may then be adsorbed, for
example, on a suitable support and then desorbed.
[0014] As described in EP 849.252, in order to obtain high purity
lactic acid, multiple crystallisations are generally carried out,
firstly of the calcium lactates in order to remove the soluble
impurities from the fermentation medium, and then of the calcium
sulphates liberated after treatment with sulphuric acid.
[0015] These crystallisation steps are followed by numerous
complementary extraction steps with ether or by a long chain amine,
combined with purification steps by ion exchange chromatography,
electrodialysis, and hydrolysis reactions in order to obtain a high
purity lactic acid.
[0016] The first disadvantage of this method which is, admittedly,
effective in terms of yield, is the high sulphuric acid consumption
and above all the production of large amounts of gypsum which poses
serious problems in terms of waste treatment and biodegradability
for the environment.
[0017] The second disadvantage is the complexity and the high
number of steps required to obtain a high purity lactic acid.
[0018] Other methods have, therefore, been proposed, leading to the
crystallisation of salts of lactic acid.
[0019] For example, U.S. Pat. No. 5,641,406 describes, after the
step involving the precipitation of calcium lactates with sulphuric
acid and the treatment with ferrocyanide or hexaferrocyanide salts
to remove the copper and iron ions, the decolourisation of the
"crude" lactic acid thus obtained with activated charcoal, and
after the subsequent purification steps to remove all the residual
salts, the concentration by evaporation and hence crystallisation
of the lactates.
[0020] Here again, this process suffers from a large number of
purification steps and the handling of toxic chemicals.
[0021] A solution to these problems was given in U.S. Pat. No.
5,210,296 by the use of a process consisting of
[0022] continuous acidification of an aqueous solution containing
ammonium lactate in the presence of an alcohol having 4 to 5 carbon
atoms used as a diluent, with sulphuric acid (or any other strong
acid),
[0023] removal of water from the acidified mixture by distillation
of the water/alcohol azeotrope and in a simultaneous or sequential
manner, removal of the ammonium sulphate crystals produced (or
salts of strong acid produced),
[0024] distillation and hydrolysis of the lactic acid ester
liberated in order to produce a free lactic acid having a purity of
more than 99.5%.
[0025] However, the difficulty of this process lies in particular
in the need to remove the ammonium sulphates. It is mentioned that
it is imperative to use alcohols having 4 to 5 carbon atoms (namely
n-butanol in this case) in order to obtain sufficiently coarse
ammonium sulphate crystals to facilitate their separation by simple
filtration of the reaction medium.
[0026] As a result, it is then possible to produce an azeotropic
water/n-butanol mixture which will be easy to remove by continuous
distillation.
[0027] It is still necessary, therefore, to proceed via the lactic
acid ester, the distillation and hydrolysis thereof in order to
obtain a lactic acid of satisfactory purity.
[0028] Consequently, the processes of the prior art all still
suffer in practice from this succession of numerous and cumbersome
steps which make the purification of lactic acid from an aqueous
solution containing lactic acid in the form of salt(s) particularly
long and tedious.
[0029] It is evident from the above that there is an unsatisfied
need for a simpler and cheaper process which permits the
separation, concentration and purification of a high purity lactic
acid with an excellent yield from an aqueous solution containing
lactic acid in the form of salt(s).
[0030] Anxious to develop a process which will satisfy the
practical limitations better than those that already exist, the
Applicant company observed that this objective could be achieved by
a process which consists in carrying out, on an aqueous solution
containing lactic acid in the form of salt(s), an acidification of
said aqueous solution and crystallisation under particular
conditions of the salts of the strong acid thus produced, which
makes it possible to directly obtain a high quality, free lactic
acid.
[0031] The Applicant company has thus overcome the technical
prejudices whereby the use of a crystallisation step in a protocol
for the purification of lactic acid from an aqueous solution
containing lactic acid in the form of salt(s):
[0032] must mean crystallisation of the salt of lactic acid in
order to extract it from said medium, and only then the
acidification thereof to precipitate the salts of the strong acid
and to produce lactic acid in the free form, or,
[0033] if it entails crystallisation of the salts of the strong
acid, this must necessarily be in an alcoholic medium in order to
produce crystals of a sufficient size to allow their removal from
said medium with the simultaneous formation of the lactic acid
ester.
[0034] The process for the preparation of high purity lactic acid
from an aqueous solution containing lactic acid in the form of
salt(s) according to the invention of the Applicant company is
characterised in that:
[0035] the aqueous solution is treated with a strong acid in order
to liberate lactic acid in the free form and to produce
corresponding salts of the strong acid,
[0036] said salts of the strong acid are crystallised by
evaporative crystallisation,
[0037] the lactic acid is recovered in the free form in
solution.
[0038] The first step of the process according to the invention
consists in treating the aqueous solution containing lactic acid in
the form of salt(s) using a strong acid in order to liberate lactic
acid in the free form and to produce corresponding salts of the
strong acid.
[0039] In a preferred embodiment of the process according to the
invention, an aqueous solution containing lactic acid in the form
of salts is used, said solution being obtained from a fermentation
medium for a lactic acid-producing microorganism. Said
microorganisms are removed from this fermentation medium by any
method known to the skilled person.
[0040] The lactic acid-producing microorganisms are selected
without discrimination and particularly from the group consisting
of Lactobacillus, Lactococcus, Enterococcus, Pediococcus,
Vagococcus, Tetragenococcus, Aerococcus, Rhizopus, Bacillus,
Streptococcus and Bifidobacterium. The composition of their
fermentation medium is widely described in the prior art.
[0041] The pH of the fermentation medium is adjusted to a value in
the range from, for example, 5 to 7, by continuously feeding the
fermentation medium with a base selected preferably from the group
consisting of NaOH, MgCO.sub.3, Na.sub.2CO.sub.3, Ca(OH).sub.2,
CaCO.sub.3, KOH and NH.sub.40H, and is preferably NH.sub.4OH or
NaOH.
[0042] Lactic acid is present in the form of an alkaline earth
metal salt selected from the group consisting of ammonium,
magnesium, calcium, sodium and potassium and is preferably ammonium
or sodium.
[0043] According to the invention, the lactic acid contained in the
fermentation medium is, therefore, partly or wholly in the form of
ammonium salt(s) or sodium salt(s).
[0044] The separation of said lactic acid-producing microorganisms
from the other constituents of the fermentation medium may consist
in microfiltration, centrifugation or precipitation of said
microorganisms by flocculating agents. These methods may also be
combined.
[0045] In the process according to the invention, a microfiltration
method is preferred, said method using a microfiltration membrane
the porosity of which is adapted to the size of the microorganisms
considered, for example, TECHSEP membranes having a porosity of 0.1
.mu.m for lactic acid-producing microorganisms of the Lactobacillus
type.
[0046] There follows advantageously a step to remove nonionic or
slightly ionic constituents from the fermentation medium that are
still present in the aqueous solution from which the microorganisms
have been removed, by a method selected from the group of
nanofiltration and/or conventional electrodialysis methods, as will
be illustrated by examples below.
[0047] These nonionic constituents mean, in this case, chiefly
proteins and sugars which have not been fully assimilated by the
lactic acid-producing microorganisms.
[0048] The conventional electrodialysis step consists, for example,
in treating a fermentation medium from which its biomass has been
removed, containing from 5 wt. % to 15 wt. % of lactate and
coproducts of fermentation, in a conventional electrodialysis
module in order to recover a solution enriched with lactates and
salts and from which nonionic or slightly ionic compounds have been
removed.
[0049] The solution of ammonium or sodium lactate which is then
recovered at the outlet of conventional electrodialysis has, for
example, a dry matter content in the range from 4 wt. % to 15 wt.
%, preferably from 5 wt. % to 10 wt. %
[0050] This solution is then advantageously concentrated to obtain
a dry matter content of at least 30 wt. %, preferably from 30 wt. %
to 50 wt. %, by any method known to the skilled person.
[0051] The solution of ammonium or sodium lactate thus concentrated
is then acidified using a strong acid. The acid selected is
advantageously 98% sulphuric acid, and the pH of the reaction
medium is brought to a value in the range from 2 to 4, preferably
to a value of 2.5.
[0052] This acidification reaction leads to the separation of
lactic acid in the free form and to the production of corresponding
salts of the strong acid, namely ammonium sulphates or sodium
sulphates in this case.
[0053] The second step of the process according to the invention
then consists in crystallising, by evaporation, said salts of the
strong acid and more particularly the ammonium or sodium sulphates
in this case.
[0054] This step consists in carrying out evaporative
crystallisation of the aqueous solution containing the mixture of
free lactic acid and ammonium sulphates or sodium sulphates, in
order to allow the specific crystallisation of the ammonium or
sodium sulphates, leaving the free lactic acid in solution in the
aqueous mother liquor.
[0055] The reaction is stopped when the system no longer appears to
evaporate water.
[0056] The crystalline mass thus obtained may then be separated
from the free lactic acid in solution by a method selected from the
group of filtration and centrifugation methods, and is preferably
the method of centrifugation.
[0057] The evaporative crystallisation conditions are selected in
such a way as to obtain a fraction composed of free lactic acid
having a dry matter content having a value at least equal to 70 wt.
%, preferably at least equal to 90 wt. %, and a fraction containing
at least 90 wt. % of ammonium or sodium sulphate in the crystalline
form, as will be shown by examples below.
[0058] Finally, a final step may be carried out, consisting of
removing the last impurities present in the fraction composed of
free lactic acid having a dry matter content reduced to a value at
least equal to 10 wt. %, preferably at least equal to 25 wt. %.
Said impurities are composed chiefly of ions, for example,
ammonium, which the various above-mentioned treatments were unable
to remove completely, and of residual sulphates.
[0059] The choice is thus made advantageously to:
[0060] a) demineralise the solution thus obtained over a strong
cationic resin followed by a slightly basic anionic resin,
[0061] b) concentrate the lactic acid thus purified.
[0062] The first step consists in removing all the inorganic salts
by passing them over two resins: a strong cationic resin then a
weak anionic resin.
[0063] In the second step, the resulting solution is concentrated
in order to bring it to a dry matter content at least equal to 90
wt. %.
[0064] Surprisingly and unexpectedly, the analysis of the lactic
acid separated and purified in this way revealed a quality which
satisfies the pharmaceutical standards of purity (conforming to
"The United States Pharmacopeia") and complies with the standards
of the "Food Chemicals Codex".
[0065] Other features and advantages of the invention will become
apparent from reading the examples below. They are, however, given
here only by way of non-limiting example.
EXAMPLE 1
[0066] The starting medium was a Lactococcus fermentation medium
containing 82 g/l of lactic acid in the form of ammonium lactates,
0.8% of proteins and 0.5% of residual sugars, from which medium its
microorganisms had been removed by microfiltration. 650 l of this
solution fed an electrodialysis module of the EUR6B EURODIA type
fitted with ion exchange membranes (NEOSEPTA-TOKUYAMA SODA) of the
CMX-S cationic type and AMX Sb anionic type having an active
surface area of 5.6 m.sup.2, following the operating parameters
defined by the manufacturer, at 35.degree. C. in such a way as to
obtain a rate of recovery of lactic acid in the form of ammonium
lactates of 98%.
[0067] The solution electrodialysed in this way made it possible to
recover, in the fraction enriched with ammonium lactates, 90% of
lactic acid in its salt form.
[0068] This solution was concentrated by evaporation under vacuum
at a pressure of 0.9 bar and at a temperature of 60.degree. C. in a
falling film evaporator of the WIEGAND type.
[0069] The concentrated solution thus obtained (120 l with a
content of 40 wt. % based on dry product) was acidified with 98%
H.sub.2SO.sub.4 to a pH of 2.5.
[0070] This acidified solution then underwent an evaporative
crystallisation step consisting of drawing off, under vacuum, the
residual water with agitation at a fixed pressure of 0.8 bar at a
temperature of 60.degree. C.
[0071] Evaporative crystallisation was carried out for 10 h.
[0072] At the end of evaporative crystallisation, 52 kg of a
crystalline mass containing 36 wt. % of individual ammonium
sulphate crystals were obtained.
[0073] A centrifugation step in a ROUSSELET type horizontal
centrifuge allowed the separation of the ammonium sulphate crystals
from the lactic solution in the purified free form.
[0074] Said solution of lactic acid was recovered in a dry matter
content of 95% for a lactic acid concentration of 95%.
[0075] Said solution was then reduced to a dry matter content of 25
wt. % and demineralised over strong cationic and weak anionic
resins by any method known to the skilled person.
[0076] The lactic acid demineralised in this way was concentrated
by evaporation in order to bring it to a dry matter content of 90
wt. %.
[0077] The lactic acid separated and purified in this way revealed
a quality which satisfies the pharmaceutical standards of purity
(in conformity with "The United States Pharmacopeia") and complies
with the standards of the "Food Chemicals Codex". More
particularly, the analysis revealed an L lactic acid content of
97.5%, an ash content of less than 0.1%. Moreover, the tests for
"readily carbonisable substance", "organic acids" and "reducing
sugar content" comply with the required specifications.
EXAMPLE 2
[0078] The procedure was the same as that described in example 1,
starting with a Lactococcus fermentation medium containing 80 g/l
of lactic acid in the form of sodium lactates, 0.9% of proteins and
0.4% of residual sugars, from which medium its microorganisms had
been removed by microfiltration.
[0079] 207 l of this solution fed an electrodialysis module of the
EUR6B EURODIA type fitted with ion exchange membranes
(NEOSEPTA-TOKUYAMA SODA) of the CMX-S cationic type and AMX Sb
anionic type having an active surface area of 5.6 m.sup.2,
following the operating parameters defined by the manufacturer, at
35.degree. C., in such a way as to obtain a rate of recovery of
lactic acid in the form of sodium lactates of 97%.
[0080] The solution electrodialysed in this way made it possible to
recover, in the fraction enriched with sodium lactates, 90% of
lactic acid in its salt form.
[0081] This solution was concentrated by evaporation under vacuum
at a pressure of 0.9 bar and at a temperature of 60.degree. C. in a
falling film evaporator of the WIEGAND type.
[0082] The concentrated solution thus obtained (41.5 l with a
content of 40 wt. % based on dry product) was acidified with 98%
H.sub.2SO.sub.4 to a pH of 2.5.
[0083] This acidified solution then underwent an evaporative
crystallisation step consisting of drawing off, under vacuum, the
residual water with agitation at a fixed pressure of 0.8 bar at a
temperature of 60.degree. C.
[0084] Evaporative crystallisation was carried out for 10 h.
[0085] At the end of evaporative crystallisation, 19 kg of a
crystalline mass containing 40 wt. % of individual sodium sulphate
crystals were obtained.
[0086] A centrifugation step in a ROUSSELET type horizontal
centrifuge allowed the separation of the sodium sulphate crystals
from the lactic solution in the purified free form.
[0087] Said solution of lactic acid was recovered in a dry matter
content of 95% for a lactic acid concentration of 95%.
[0088] Said solution was then reduced to a dry matter content of 25
wt. % and demineralised over strong cationic and weak anionic
resins by any method inherently known to the skilled person.
[0089] The lactic acid demineralised in this way was concentrated
by evaporation in order to bring it to a dry matter content of 90
wt. %.
[0090] The lactic acid separated and purified in this way revealed
a quality which satisfies the pharmaceutical standards of purity
(in conformity with "The United States Pharmacopeia") and complies
with the standards of the "Food Chemicals Codex". More
particularly, the analysis revealed an L lactic acid content of
98%, an ash content of less than 0.1%. Moreover, the tests for
"readily carbonisable substance", "organic acids" and "reducing
sugar content" comply with the required specifications.
* * * * *