Chemistry: molecular biology and microbiology – Micro-organism – tissue cell culture or enzyme using process... – Preparing oxygen-containing organic compound
Reexamination Certificate
2000-10-13
2001-08-28
Weber, Jon P. (Department: 1651)
Chemistry: molecular biology and microbiology
Micro-organism, tissue cell culture or enzyme using process...
Preparing oxygen-containing organic compound
C435S136000
Reexamination Certificate
active
06280985
ABSTRACT:
TECHNICAL FIELD
The present invention relates to a specific process for the separation and purification of lactic acid from a fermentation medium.
In particular, the present invention relates to a process for the preparation of lactic acid with a quality which enables it to be used not only in sectors such as the fields of food applications and the chemical, agrochemical, plastics and cosmetics industries, but also especially in the fields of pharmaceutical applications.
BACKGROUND
Lactic acid is normally prepared by the fermentation of microorganisms of the genera Lactobacillus (
L. acidophilus, L. delbrüeckii, L. pentosus
etc.), Rhizopus, Bacillus (
B. coagulans
etc.), Streptococcus etc.
However, it is known that the growth, or even the viability, of the majority of these lactic acid-producing microorganisms is inhibited by the drop in the pH of the fermentation medium, this strong acidification of the medium being caused by the production of organic acids, including lactic acid itself.
It is therefore necessary to regulate the pH and it is generally acknowledged that it has to be maintained at a value of between 4 and 7, preferably of more than 4.5, for example of between 5.5 and 6.5, by the addition of bases such as alkali metal or alkaline earth metal hydroxides, or carbonates or bicarbonates.
The lactic acid is therefore present in these fermentation media in the form of salts (sodium, potassium, calcium or ammonium lactates, individually or in a mixture, depending on the base chosen for regulating the pH of the fermentation medium).
Thus all the methods of recovering the lactic acid from the fermentation media have to solve the same difficulties, i.e. separating the lactic acid salt(s), the microorganisms which produced them and the impurities in the fermentation medium (unconsumed sugars and proteins and various kinds of inorganic salts) as well as converting the lactic acid salts to lactic acid in the free form, which also requires the subsequent removal of the corresponding base generated.
Various methods have been proposed for recovering lactic acid from a fermentation medium.
It is quite generally known to purify lactic acid from lactates by the addition of sulfuric acid.
For example, if the pH of the fermentation medium is regulated with carbonates or bicarbonates, the lactic acid in the free form can be recovered by acidification of the medium with sulfuric acid.
The reaction gives rise to the formation of calcium sulfates (gypsum), which precipitate, and to the release of lactic acid in the free form, which can then be extracted with an organic solvent or adsorbed onto a suitable support and then desorbed.
However, the disadvantage of this method, which is otherwise efficient in terms of yield, is the high consumption of sulfuric acid and especially the production of large amounts of gypsum, which presents serious environmental problems in terms of waste treatment and biodegradability.
Patent JP 63/188,632 describes the regulation of the pH of the fermentation medium with zinc hydroxide to give a zinc lactate of low solubility, allowing it to be purified by crystallization.
The major disadvantage here is the need to use hydrogen sulfide, which is not easy to handle; in particular, this process gives poor crystallization yields due to excessive loss of product in the mother liquor.
Another process consists in carrying out an adsorption/desorption with a trialkylamine. For example, patent DE 2,329,480 describes a liquid-liquid extraction (or LLE) process which consists in extracting the lactic acid by means of a water-immiscible organic solvent in the presence of at least one Lewis base such as a tertiary amine. The lactic acid has to be recovered in a second liquid-liquid extraction step, in which it is transferred back into the water.
However, the disadvantage is in the formation of trialkylammonium lactates with pKa values of about 9 to 11, so the energy required to release the acid form is prohibitive.
By extension, any processes which require the decomposition of trialkylammonium salts to the corresponding acids consume large amounts of energy.
The use of NH
4
OH or NaOH to regulate the pH of the fermentation medium is also described, said process making it possible to avoid the need for sulfuric acid and to recover the lactates more cleanly in the form of ammonium or sodium lactates. It is then possible to carry out an ultrafiltration step to separate said lactates from the other components of the fermentation medium, and finally to obtain the lactic acid by carrying out a separation step on ion exchange resins.
This process employs membrane and ion exchange methods by which lactic acid cannot be obtained in high purity.
Two approaches were developed to overcome this difficulty: a first approach involves chromatographic separation, especially on a strong cation exchange resin; the second involves separation by concentrating or desalinating electrodialysis and/or by bipolar fractionating electrodialysis.
According to the first approach, it was proposed to bring the medium containing e.g. sodium lactate into direct contact with a strong cation exchange resin of the hydrogen type, in the liquid form, in order to remove the sodium ions.
However, this process consumes large amounts of resins and hydrochloric or sulfuric acids to regenerate said resin, and is difficult to carry out on the industrial scale.
Patent EP 483,831 offers an alternative to this process by carrying out the separation of an organic acid (or organic acids) and inorganic salts using chromatography columns.
The process described consists in cultivating a lactic acid-producing microorganism in a fermentation medium containing glucose as the carbon source, and chromatographing said fermentation medium, containing sugars, inorganic salts and other residual impurities as well as an organic acid (or organic acids), under specific conditions.
More precisely, the process consists in passing said starting fermentation medium, containing the organic acid (or organic acids), through a column containing the cation exchange resin, resulting in the retention of said organic acid (or said acids) on the column. An eluent of the mineral acid type is then passed through in order to desorb any organic acid. In the case where it is desired to separate several organic acids (such as tartaric acid and gluconic acid), an additional step consists in separating the acids from the resulting eluate.
The description states that it is absolutely essential for the pH to be below the pKa of the acid in question.
More particularly, an example is given of a process for the preparation of lactic acid from an
L. delbrüeckii
fermentation medium, the pH of the medium being regulated to 5.8 with NaOH.
The microorganisms are removed from said medium, containing 71 g/l of sodium lactate, and the medium is then acidified to pH 1.6 with sulfuiric acid. Said acidified solution is then passed through a chromatography column in which the cationic resin has first been equilibrated to pH 3.09 by the passage of dilute sulfuric acid. The column is then eluted with more sulfuric acid, still at a pH below the pKa of lactic acid. i.e. below 3.87, making it possible to recover one fraction containing sodium sulfate and another fraction containing lactic acid.
However, this process again requires the use of large amounts of sulfuric acid, both to lower the pH of the fermentation medium and maintain the pH in the chromatography column, and also to adjust the pH of the eluent to a value below the pKa of lactic acid.
The more it is desired to lower the pH, so as not only to limit the proportion of lactic acid salts in equilibrium with the free lactic acid formed, but also to limit the loss of free lactic acid with the impurities (residual sugars, proteins and inorganic salts in the fermentation medium) which are normally eluted in the first fractions of the chromatographic separation, as furthermore deplored in patent EP 483,831, the larger these amounts of sulfuric acid will be.
According to the second approach, the preferred procedure is to
Caboche Jean-Jacques
Choque Jean-Christophe
Dubois Eric
Duflot Pierrick
Fouache Catherine
Guttman Harry J
Henderson & Sturm LLP
Roquette Freres
Weber Jon P.
LandOfFree
Process for the separation and purification of lactic acid... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Process for the separation and purification of lactic acid..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Process for the separation and purification of lactic acid... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2491996