SK62599A3 - Process for the separation of tetrahydropyrimidin derivatives - Google Patents

Process for the separation of tetrahydropyrimidin derivatives Download PDF

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Publication number
SK62599A3
SK62599A3 SK62599A SK62599A SK62599A3 SK 62599 A3 SK62599 A3 SK 62599A3 SK 62599 A SK62599 A SK 62599A SK 62599 A SK62599 A SK 62599A SK 62599 A3 SK62599 A3 SK 62599A3
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compounds
adsorption
solution
zeolites
separated
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SK62599A
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Slovak (sk)
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Stefan Stockhammer
Wiltrud Treffenfeldt
Andrea Preuss
Andreas Karau
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Degussa
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/06—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D61/00—Processes of separation using semi-permeable membranes, e.g. dialysis, osmosis or ultrafiltration; Apparatus, accessories or auxiliary operations specially adapted therefor
    • B01D61/02—Reverse osmosis; Hyperfiltration ; Nanofiltration
    • B01D61/027—Nanofiltration
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D61/00—Processes of separation using semi-permeable membranes, e.g. dialysis, osmosis or ultrafiltration; Apparatus, accessories or auxiliary operations specially adapted therefor
    • B01D61/02—Reverse osmosis; Hyperfiltration ; Nanofiltration
    • B01D61/04—Feed pretreatment
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D61/00—Processes of separation using semi-permeable membranes, e.g. dialysis, osmosis or ultrafiltration; Apparatus, accessories or auxiliary operations specially adapted therefor
    • B01D61/14—Ultrafiltration; Microfiltration
    • B01D61/147—Microfiltration
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D61/00—Processes of separation using semi-permeable membranes, e.g. dialysis, osmosis or ultrafiltration; Apparatus, accessories or auxiliary operations specially adapted therefor
    • B01D61/14—Ultrafiltration; Microfiltration
    • B01D61/16—Feed pretreatment
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D2311/00—Details relating to membrane separation process operations and control
    • B01D2311/04—Specific process operations in the feed stream; Feed pretreatment

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  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Water Supply & Treatment (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Chemistry (AREA)
  • Nanotechnology (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Solid-Sorbent Or Filter-Aiding Compositions (AREA)
  • Treatment Of Liquids With Adsorbents In General (AREA)

Abstract

Ectoin and hydroxyectoin produced by cultured Halomonas bacteria can be separated whilst in aqueous solution using an acidic zeolite. The ectoin is absorbed, while the hydroxy compound remains in solution. Separating tetrahydropyrimidine derivatives from their corresponding hydroxy compounds when in aqueous solution, comprises contacting the solution with an acidic zeolite at pH 1.0-7.0 (the zeolite has a modulus of 15-1000). The hydroxy compounds remain in solution, while the tetrahydropyrimidine compounds are absorbed by the zeolite, and can be desorbed by contacting with a solution of an organic base at pH of at least 8.0.

Description

Spôsob oddeľovania derivátov tetrahydropyrimidinuMethod for separating tetrahydropyrimidine derivatives

Oblasť technikyTechnical field

Vynález sa týka spôsobu oddeľovania tetrahydropyrimidínových derivátov, najmä 2-metyl-l,4,5,6-tetrahydropyrimidín-The invention relates to a process for separating tetrahydropyrimidine derivatives, in particular 2-methyl-1,4,5,6-tetrahydropyrimidine-

4-karboxylových kyselín (ektoinov) a 2-metyl-5-hydroxy1, 4, 5, 6-tetrahydropyrimidín-4-karboxylových kyselín (hydroxyektoínov), ktoré spolu sa nachádzajú vo vodných roztokoch, selektívnou adsorpciou jednej zložky na zeolitoch.4-carboxylic acids (ectoines) and 2-methyl-5-hydroxy-1,4,5,6-tetrahydropyrimidine-4-carboxylic acids (hydroxy-actoins), which are found together in aqueous solutions, by selective adsorption of one component on the zeolites.

Doterajší stav technikyBACKGROUND OF THE INVENTION

Tetrahydropyrimidínovými derivátmi sa mienia najmä zlúčeniny známe z EP-A1-0553884.Tetrahydropyrimidine derivatives are particularly meant the compounds known from EP-A1-0553884.

Štruktúrne sú ektoíny cyklickými aminokyselinovými derivátmi, ktoré patria do triedy takzvaných „kompatibilných rozpustených látok. Sú kompatibilné aj vo vysokej koncentrácii 'S cytoplazmou a stabilizujú bunkové zložky v prostredí malej aktivity vody. Toto pôsobenie poukazuje na široké pole použitia v odboroch medicíny a kozmetiky.Structurally, ectoines are cyclic amino acid derivatives that belong to the class of so-called "compatible solutes". They are also compatible at high concentrations with the cytoplasm and stabilize cellular components in an environment of low water activity. This action points to a wide field of application in the fields of medicine and cosmetics.

Pomocou nových biotechnologických spôsobov sa podarilo vypestovať halofilné eubaktérie, napríklad rodu Halomonas, a vyvolať u týchto organizmov vylučovanie ektoinov do prostredia, ktoré ich obklopuje (T. Sauer et al. GIT Fachz. Lab. 10/95).New biotechnological methods have been used to grow halophilic eubacteria, such as the genus Halomonas, and to induce the secretion of ectoins into the surrounding environment (T. Sauer et al. GIT Fachz. Lab. 10/95).

Pretože v závislosti od fermentačných podmienok sa produkujú ektoíny aj hydroxyektoíny, v nasledujúcich krokoch spracovania sa vyžaduje oddelenie obidvoch zložiek, aby sa získali čisté zložky. Toto oddelovanie sa môže uskutočňovať napríklad extrakciou metanolom využívaním odlišných rozpustností ektoínu a hydroxyektoínu. (T. Sauer a Erwin A. Galinski. Biotechnology and Bioengineering, VOL 57, NO 3, 1998) . Tento spôsob je však v technickom meradle v dôsledku značných množstiev potrebného metanolu nákladný.Since, depending on the fermentation conditions, both ectoines and hydroxyectoins are produced, the subsequent processing steps require separation of both components to obtain pure components. This separation can be carried out, for example, by extraction with methanol using different solubilities of ectoine and hydroxyectoin. (T. Sauer and Erwin A. Galinski. Biotechnology and Bioengineering, VOL 57, NO 3, 1998). However, this process is expensive on a technical scale due to the considerable amounts of methanol required.

Úlohou vynálezu je poskytnutie alternatívneho spôsobu, ktorý umožňuje efektívne oddelovanie derivátov tetrahydropyrimidínu, najmä ektoínov a hydroxyektoínov, z vodného roztoku, poprípade obsahujúceho ďalšie organické a anorganické zlúčeniny, bez použitia rozpúšťadiel.SUMMARY OF THE INVENTION It is an object of the present invention to provide an alternative process which allows the effective separation of tetrahydropyrimidine derivatives, in particular ectoines and hydroxyoctoins, from an aqueous solution optionally containing other organic and inorganic compounds without the use of solvents.

Podstata vynálezuSUMMARY OF THE INVENTION

Predmetom vynálezu je spôsob oddeľovania derivátov tetrahydropyrimidínu, nachádzajúcich sa vo vodnom roztoku, ť 1 od príslušných hydroxyzlúčenín, najmä 2-metyl-l,4,5,6-tetrahydropyrimidín-4-karboxylových kyselín (ektoíny (I)) a 2metyl-5-hydroxy-l,4,5,6-tetrahydropyrimidín-4-karboxylových kyselín (hydroxyektoíny) (II), ktoré sa spolu nachádzajú vo vodných roztokoch, vyznačujúci sa tým, že sa vodné roztoky, ktoré obsahujú obidve zložky, pri hodnote pH 1,5 až 7,0 privedú do kontaktu s prednostne kyslým zeolitom, ktorý má modul 15,až 1000. Pritom nastáva kinetický prednostná adsorpcia ektoínu oproti hydroxyektoínu. Optimálnym nastavením experimentálne stanoviteľného času kontaktu medzi zeolitom a roztokom nastáva selektívne ochudobnenie východiskového roztoku o ektoín, zatiaľ čo hydroxyektoín najprv zostáva v roztoku a až pri dlhších časoch kontaktu sa adsorbuje vo významnom množstve. Deriváty ektoínu naviazané na zeolite sa desorbujú z použitého zeolitu nastavením hodnoty pH na hod notu väčšiu ako 8,0, najmä použitím roztoku hydroxidu amónneho. Roztok sa môže nastaviť na túto hodnotu pH aj pridaním inej zásaditej, poprípade organickej zložky, najmä lyzínu.The present invention is a process for the separation of tetrahydropyrimidine derivatives, contained in the aqueous solution, t 1 from the respective hydroxy compounds, especially 2-methyl-l, 4,5,6-tetrahydropyrimidine-4-carboxylic acid (ectoines (I)) and 2-methyl-5- hydroxy-1,4,5,6-tetrahydropyrimidine-4-carboxylic acids (hydroxy-actoins) (II), which are present together in aqueous solutions, characterized in that the aqueous solutions containing both components are at a pH of 1, 5 to 7.0 contact with a preferably acidic zeolite having a modulus of 15 to 1000. In this case, kinetic preferential adsorption of ectoine over hydroxyectoin occurs. By optimally setting the experimentally determined contact time between the zeolite and the solution, the starting solution is selectively depleted of ectoine, while the hydroxyectoin initially remains in the solution and is adsorbed in significant amounts only at longer contact times. The zeolite-bound ectoine derivatives are desorbed from the zeolite used by adjusting the pH to greater than 8.0, in particular using ammonium hydroxide solution. The solution can also be adjusted to this pH by the addition of another basic or organic component, in particular lysine.

V závislosti od potrebnej čistoty derivátov, ktoré sa majú izolovať, je potrebné poprípade tento postup čistenia uskutočniť vo viacerých za sebou nasledujúcich krokoch.Depending on the required purity of the derivatives to be isolated, this purification process may optionally be carried out in several successive steps.

Pod derivátmi tetrahydropyrimidínu, ktoré sa majú oddeľovať a čistiť podľa vynálezu, sa rozumejú najmä zlúčeniny vzorcovThe tetrahydropyrimidine derivatives to be separated and purified according to the invention are in particular meant compounds of the formulas:

kde R1 znamená H a R2 znamená OH.wherein R1 is H and R2 is OH.

Roztoky, z ktorých sa tieto látky oddeľujú, sú vo všeobecnosti vodnej alebo organickej povahy.The solutions from which they are separated are generally of an aqueous or organic nature.

Zeolitmi vhodnými na adsorpciu zlúčenín, ktoré sa majú oddeľovať podľa vynálezu, sú zeolity typu Y, DAY, mordenit, dealuminovaný mordenit, ZSM-5, dealuminovaný ZSM-5, β alebo VPI5 a s modulom 10 až 1000, najmä 15 až 200, prednostne 15 až 45. Prednostne sa používa typ ZSM-5 v H-forme, amóniovej forme alebo Na-forme.Zeolites suitable for adsorption of the compounds to be separated according to the invention are zeolites of the type Y, DAY, mordenite, dealuminated mordenite, ZSM-5, dealuminated ZSM-5, β or VPI5 and having a modulus of 10 to 1000, in particular 15 to 200, preferably 15 Preferably, the ZSM-5 type is used in the H-form, ammonium form or Na-form.

Spôsob prebieha všeobecne v teplotnom rozsahu 15 až 80 °C, prednostne 20 až 40 °C.The process is generally carried out in a temperature range of 15 to 80 ° C, preferably 20 to 40 ° C.

Koncentrácie ektoinov, poprípade hydroxyektoinov, ktoré sa majú oddeľovať, sú v známom rozsahu rozpustnosti. Pomery koncentrácii (molovo) zlúčenín, ktoré sa majú oddeľovať, bežné v stave techniky, sa dajú vypracovať pomocou spôsobu podľa vynálezu a poskytujú žiadaný pjrodukt s potrebnou čistotou. Adsorbenty sa používajú v práškovej forme, ako tvarované výrobky alebo nanesené na nosiči. Na technologickú realizáciu postupu je k dispozícii prerušovaná filtrácia, filtrácia s pevným lôžkom alebo filtrácia s priečnym tokom (crossflow-filtrácia), uskutočňovaná kontinuálne alebo diskontinuálne.Concentrations of ectoins or hydroxyectoins to be separated are within the known solubility range. Concentration ratios (molar) of the compounds to be separated, conventional in the art, can be prepared by the process of the invention and provide the desired product with the required purity. The adsorbents are used in powder form, as shaped articles or coated. Intermittent filtration, fixed bed filtration or cross-flow filtration, either continuously or discontinuously, are available for the technological implementation of the process.

Vo výhodnej forme uskutočnenia sa kombinuje adsorpcia na zeolite s filtráciou s priečnym, tokom, pri ktorej sa roztok obsahujúci deriváty tetrahydropyrimidinu, popripade zbavený biomasy, privedie do kontaktu so suspenziami kyslého zeolitu na časový interval zodpovedajúci adsorpčnej kinetike a hneď potom sa deriváty hydroxytetrahydropyrimidinu, nachádzajúce sa vo zvyšnej kvapaline, oddelia filtráciou s priečnym tokom tým, žeIn a preferred embodiment, adsorption on zeolite is combined with a cross-flow filtration, wherein a solution containing tetrahydropyrimidine derivatives, optionally de-biomassed, is contacted with acid zeolite suspensions for a period of time corresponding to the adsorption kinetics and immediately thereafter the hydroxytetrahydropyrimidine derivatives present. in the remaining liquid, separated by cross - flow filtration by

a) sa nasýtené zeolity vo forme suspenzii nechajú pretekať popri pórovitej ploche/membráne, pričom saa) the saturated zeolites in the form of suspensions are allowed to flow along the porous surface / membrane, whereby

b) rozdiel tlaku medzi prepúšťacou stranou a protiľahlou stranou plochy/membrány sa nastavi tak, že(b) the pressure difference between the leakage side and the opposite side of the surface / membrane is adjusted so that:

c) časť roztoku obsahujúceho hydroxyzlúčeniny, pretekajúceho plochou/membránou, čiastočne alebo úplne zbaveného adsorbovaných zlúčenín, prúdi plochou/membránou priečne k smeru toku (tok filtrátu),c) part of the solution containing hydroxyl compounds flowing through the surface / membrane, partially or completely free of adsorbed compounds, flows through the surface / membrane transversely to the flow direction (filtrate flow),

d) v kroku premývania sa oddelí roztok zbavený adsorbovaných zlúčenín, ktorý obsahuje hydroxyzlúčeniny, ad) separating the adsorbed compound containing the hydroxy compounds in the washing step; and

e) hneď potom sa adsorbované zlúčeniny desorbujú.e) immediately afterwards the adsorbed compounds are desorbed.

Posledný krok nastáva pri vhodnej hodnote pH, najmä pri hodnote pH väčšej ako 8,0.The last step occurs at a suitable pH, particularly at a pH greater than 8.0.

Ako adsorbenty sú obzvlášť vhodné jemnozrnné zeolitové prášky horeuvedených typov s priemerom častíc 1 až 100 pm, najmä 2 až 20 pm. Krátke intrapartikulárne difúzne dráhy umožňujú vysokú selektivitu pri adsorpcii, a tým vysoké rozdeľovacie faktory.Particularly suitable adsorbents are fine-grained zeolite powders of the abovementioned types with a particle diameter of 1 to 100 µm, in particular 2 to 20 µm. Short intraparticular diffusion pathways allow high selectivity in adsorption and thus high partitioning factors.

Dosiahnuté čistoty pre hydroxyektoín vo zvyšnej kvapaline (vzhľadom na celkové množstvo ektoínov) sú pri použití napríklad ZSM5/28 po čase kontaktu 1 h približne 100 % (príklad 1). Pri mordenite 30 sú čistoty po 24 h na základe pomalšej kinetiky približne 60 % (príklad 2). Môžu sa však pri vhodnej kombinácii krokov spôsobu zvýšiť.The achieved purities for the hydroxyectoin in the remaining liquid (relative to the total amount of ectoines) are, for example, ZSM5 / 28 after a contact time of 1 h approximately 100% (Example 1). At mordenite 30, the purities after 24 h are about 60% based on slower kinetics (Example 2). However, they can be increased by a suitable combination of process steps.

Na zvýšenie čistoty sa roztoky prevedú raz alebo viackrát postupom čistenia podlá vynálezu. Jeden variant spôsobu podľa vynálezu spočíva v tom, že toto sa kombinuje s čistením známym z doterajšieho stavu techniky použitím organických katexov a iných krokov čistenia.To increase the purity, the solutions are carried out one or more times by the purification process according to the invention. One variant of the process according to the invention is that this is combined with the prior art purification using organic cation exchangers and other purification steps.

Príslušný krok adsorpcie a desorpcie sa uskutočňuje pred a/alebo po stupni čistenia adsorpciou na zeolite použitom podlá vynálezu, po ktorom nasledovala desorpcia.The respective adsorption and desorption step is carried out before and / or after the zeolite adsorption purification step used according to the invention, followed by desorption.

Príklady uskutočnenia vynálezuDETAILED DESCRIPTION OF THE INVENTION

Príklad 1Example 1

Adsorpcia zmesi ektoínu a hydroxyektoínu na ZSM5 /28Adsorption of mixture of ectoine and hydroxyectoin on ZSM5 / 28

Časové priebehy koncentrácie ektoínu a hydroxyektoínu a čistota hydroxyektoínu (vzhladom na celkové množstvo ektoínu)Time courses of the concentration of ectoine and hydroxyectoin and the purity of hydroxyectoin (relative to the total amount of ectoine)

Zloženie východiskového roztokuComposition of the starting solution

Objem kvapaliny (ml) Liquid volume (ml) 30 30 Koncentrácia zeolitu (% hmotn.) Zeolite concentration (wt%) 10 10 Koncentrácia ektoínu (g/1) Ectoin concentration (g / l) 1,5 1.5 Koncentrácia hydroxyektoínu (g/1) Hydroxyectoin concentration (g / l) 0,14 0.14

ostatné prímesi (g/1) približne 1other impurities (g / l) approximately 1

1,00 0-0—0—0—0—0O— 100,001.00 0-0—0—0—0—0O— 100,00

0,800.80

Δ Ektoin ,Δ Ektoin,

O Hydroxyektoín □Čistota hydroxyektoínuO Hydroxyectoin □ Hydroxyectoin purity

0,600.60

0,400.40

60,0060.00

40,0040.00

Čistota hydroxyektoínu [%]Hydroxyectoin purity [%]

0,200.20

20,0020.00

-410-410

Λ.Λ.

-+15 á— 0.00- + 15 and - 0.00

ΊΊ

Príklad 2Example 2

Adsorpcia zmesi ektoínu a hydroxyektoínu na mordenite 30 Časové priebehy koncentrácie ektoínu a hydroxyektoínu a čistota hydroxyektoínu vo zvyšnej kvapaline (vzhľadom na celkové množstvo ektoínu)Adsorption of the Ectoin and Hydroxytotoin mixture at the mordenite 30 Time courses of the Ectoin and Hydroxytotoin concentration and the purity of the Ectoin in the remaining liquid (relative to the total amount of Ectoin)

Zloženie východiskového roztokuComposition of the starting solution

Objem kvapaliny (ml) Liquid volume (ml) 30 30 Koncentrácia zeolitu (% hmotn.) Zeolite concentration (wt%) 10 10 Koncentrácia ektoínu (g/1) Ectoin concentration (g / l) 1/5 1/5 Koncentrácia hydroxyektoínu (g/1) Hydroxyectoin concentration (g / l) 0,14 0.14

ostatné primesi (g/1) približne 1other admixtures (g / l) approximately 1

1.001:00

0,00 o0,00 o

0,800.80

0,600.60

0.4000:40

0,200.20

Q OQ O

O O o o o OO oo o o about ÄEktoin O Hydroxyektoin OČistota hydroxyektoínu ÄEktoin O Hydroxyectoin The purity of the hydroxyectoin Δ Δ Δ 1 , Δ Δ 1,  Δ o about Δ Δ Δ ô O Δ ô ABOUT o o° ► -------------------------------------------------------1--------------------------------------------------------1-------------------------------------- about o ° ► -------------------------------------------------- 1 -------------------------------------------- ----- 1 ------------ ------------------------------------- - - 1------------------------------1 - 1 ------------------------------ 1 Δ Δ

100.00100.00

80,0080.00

60,0060.00

40,0040.00

20,0020.00

1515

Čas [h]Time [h]

0,000.00

Claims (14)

PATENTOVÉ NÁROKYPATENT CLAIMS 1. Spôsob oddeľovania derivátov tetrahydropyrimidínu, nachádzajúcich sa vo vodnom roztoku, od príslušných hydroxyzlúčenín, vyznačujúci sa tým, že sa vodné roztoky týchto zlúčenín privedú pri hodnote pH 1,0 až 7,0 do kontaktu s kyslým zeolitom, ktorý má modul 15 až 1000, po uskutočnenej adsorpcii sa oddelí zvyšná kvapalina, obsahujúca prednostne hydroxyzlúčeniny, a adsorbované deriváty sa desorbujú zo zeolitov vodným roztokom, nastaveným na hodnotu pH väčšiu ako 8,0, poprípade pridaním zásaditej organickej zložky.Process for separating tetrahydropyrimidine derivatives present in aqueous solution from the corresponding hydroxy compounds, characterized in that aqueous solutions of these compounds are brought into contact with an acid zeolite having a modulus of 15 to 1000 at a pH of 1.0 to 7.0. After adsorption, the remaining liquid, preferably containing hydroxy compounds, is separated and the adsorbed derivatives are desorbed from the zeolites with an aqueous solution adjusted to a pH greater than 8.0, optionally by addition of a basic organic component. 2. Spôsob podľa nároku 1, vyznačujúci sa tým, že sa oddeľuje zmes 2-metyl-l,4,5,6-tetrahydropyrimidin-4-karboxylových kyselín (ektoiny) všeobecného vzorca kde R1 znamená H a R2 znamená OH, nachádzajúca sa vo vodnom roztoku.Process according to claim 1, characterized in that a mixture of 2-methyl-1,4,5,6-tetrahydropyrimidine-4-carboxylic acids (ectoines) of the general formula wherein R 1 is H and R 2 is OH, is separated. in aqueous solution. 3. Spôsob podľa nárokov la2, vyznačujúci sa t ý m , že sa zvyšná kvapalina získaná po adsorpcii znova privedie do kontaktu s jedným z horeuvedených typov zeolitov, adsorbent sa hneď potom oddelí a tieto kroky sa poprípade raz alebo viackrát opakujú.Method according to claims 1 and 2, characterized in that the remaining liquid obtained after adsorption is brought back into contact with one of the above-mentioned types of zeolites, the adsorbent is then separated off immediately and these steps are repeated one or more times, if necessary. 4. Spôsob podlá nárokov 1 až 3, vyznačujúci sa t ý m , že sa ako vodný roztok používa fermentačný roztok.Method according to claims 1 to 3, characterized in that a fermentation solution is used as the aqueous solution. 5. Spôsob podlá nároku 4, vyznačujúci sa tým, že sa pred adsorpciou aspoň čiastočne oddelia z fermentačného roztoku mikroorganizmy.The method according to claim 4, characterized in that the microorganisms are separated at least partially from the fermentation solution prior to adsorption. 6. Spôsob podlá nárokov 4a 5, vyznačujúci sa t ý m , že sa pred adsorpciou aspoň čiastočne oddelia z fermentačného roztoku rozpustné proteiny.Method according to claims 4 and 5, characterized in that, before adsorption, soluble proteins are separated from the fermentation solution. 7. Spôsob podlá jedného alebo viacerých z nárokov 1 až 6, vyznačujúci sa tým, že sa ako adsorbenty používajú kyslé zeolity typu Y, DAY, mordenitu, dealuminovaného mordenitu, ZSM-5, dealuminovaného ZSM-5, β alebo VPI5 s modulom 15 až 1000.Method according to one or more of Claims 1 to 6, characterized in that acidic zeolites of type Y, DAY, mordenite, dealuminated mordenite, ZSM-5, dealuminated ZSM-5, β or VPI5 with a module 15 to 15 are used as adsorbents. 1000th 8. Spôsob podlá nároku 6, vyznačujúci sa tým, že sa používajú zeolity typu ZSM5 alebo mordenitu v H-forme, amóniovej forme alebo Na-forme.Method according to claim 6, characterized in that ZSM5-type or mordenite-type zeolites are used in the H-form, ammonium form or Na-form. 9. Spôsob podlá jedného alebo viacerých z nárokov 1 ažMethod according to one or more of claims 1 to 9 8 na oddelovanie vyššie označených derivátov tetrahydropyrimidínu, najmä vzorca (I), vyznačujúci sa tým, že sa kombinuje s fitráciou s priečnym tokom (filtrácia crossflow), pričom sa8 for separating the above-described tetrahydropyrimidine derivatives, in particular of formula (I), characterized in that it is combined with cross-flow filtration (crossflow filtration), a) sa nasýtené zeolity vo forme suspenzií nechajú pretekať popri pórovitej ploche/membráne, pričom saa) the saturated zeolites in the form of suspensions are allowed to flow along the porous surface / membrane, whereby b) rozdiel tlaku medzi prepúšťacou stranou a protiľahlou stranou plochy/membrány sa nastaví tak, že(b) the pressure difference between the leakage side and the opposite surface / membrane side is adjusted so that: c) časť roztoku obsahujúceho hydroxyzlúčeniny, pretekajúceho plochou/membránou, čiastočne alebo úplne zbaveného adsorbovaných zlúčenín/ prúdi plochou/membránou priečne k smeru toku (tok filtrátu),c) part of a solution containing hydroxyl compounds flowing through the surface / membrane, partially or completely free of adsorbed compounds / flowing through the surface / membrane transversely to the flow direction (filtrate flow), d) v kroku premývania sa oddelí roztok zbavený adsorbovaných zlúčenín, ktorý obsahuje hydroxyzlúčeniny, ad) separating the adsorbed compound containing the hydroxy compounds in the washing step; and e) hneď potom sa adsorbované zlúčeniny desorbujú.e) immediately afterwards the adsorbed compounds are desorbed. i ’i ’ I *I * 10. Spôsob podľa nároku 9, vyznačujúci sa tým, že sa používajú zeolity so stredným priemerom častíc 1 až 100 μιη.Method according to claim 9, characterized in that zeolites with a mean particle diameter of 1 to 100 μιη are used. 11. Spôsob podľa nárokov 9 a 10, vyznačujúci sa t ý m , že sa nastaví transmembránový tlak 0,2.105 až 3.105 Pa.Method according to claims 9 and 10, characterized in that the transmembrane pressure is set to 0.2.10 5 to 3.10 5 Pa. 12. Spôsob podľa nárokov 9 až 11, vyznačuj úci sa t ý m , že sa používajú keramické alebo organické membrány/pórovité plochy s ultrafiltračnými alebo mikrofiltračnými alebo nanofiltračnými vlastnosťami.Method according to claims 9 to 11, characterized in that ceramic or organic membranes / porous surfaces with ultrafiltration or microfiltration or nanofiltration properties are used. 13. Spôsob podľa jedného alebo viacerých z predchádzajúcich nárokov, vyznačujúci sa tým, že sa desorbovaný roztok podrobí raz alebo viackrát adsorpcii a desorpcii.Method according to one or more of the preceding claims, characterized in that the desorbed solution is subjected to adsorption and desorption one or more times. 14. Spôsob podlá jedného alebo viacerých z predchádzajúcich nárokov, vyznačujúci sa tým, že sa spôsob oddeľovania zlúčenín (A) kombinuje s adsorpciou na katexoch alebo s inými krokmi čistenia a s roztokmi z nich poprípade opakovane získanými desorpciou.Method according to one or more of the preceding claims, characterized in that the method of separating the compounds (A) is combined with adsorption on cation exchangers or other purification steps and with solutions therefrom optionally recovered by desorption.
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