CS274030B1 - Method of yeast /1-3/-beta-d-glucan purification - Google Patents

Method of yeast /1-3/-beta-d-glucan purification Download PDF

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CS274030B1
CS274030B1 CS3889A CS3889A CS274030B1 CS 274030 B1 CS274030 B1 CS 274030B1 CS 3889 A CS3889 A CS 3889A CS 3889 A CS3889 A CS 3889A CS 274030 B1 CS274030 B1 CS 274030B1
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glucan
beta
alpha
yeast
purified
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CS3889A
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Czech (cs)
Slovak (sk)
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CS3889A1 (en
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Ladislav Ing Csc Masler
Karol Ing Csc Babor
Jozef Rndr Csc Sandula
Grigorij Ing Csc Kogan
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Masler Ladislav
Karol Ing Csc Babor
Sandula Jozef
Grigorij Ing Csc Kogan
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Priority to CS3889A priority Critical patent/CS274030B1/en
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Publication of CS274030B1 publication Critical patent/CS274030B1/en

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Abstract

The invention concerns purification of yeast (1-3)-beta-D-glucan which also contains undesirable alpha-D-glucanes by enzymes with amylase activity, whereas alpha-D-glucanes are specifically removed without attacking and modifying the prepared (1-3)-beta-D-glucane in purified form.

Description

Riešenie sá týká purifikácie kvasinkového (1—>3)-beta-D-glukánu, ktorý obsahuje aj nežiadúce alfa-D-glukány enzýmami s amylázovou aktivitou, pričom sa Specificky odstránia alfa-D-glukány bez atakovania a modifikácie připravovaného (1-*3)-beta-D-glukánu v purifikovanej formě.The solution relates to the purification of yeast (1-> 3) -beta-D-glucan, which also contains undesired alpha-D-glucans by enzymes with amylase activity, specifically removing alpha-D-glucans without attacking or modifying the prepared (1- *) 3) -beta-D-glucan in purified form.

cs 274030 Blcs 274030 Bl

Vynález sa týká sposobu purifikácie kvasinkového (1—>3)-beta-D-glukánu znečistěného alfa-D-glukánmi.The invention relates to a method of purifying yeast (1 → 3) -beta-D-glucan contaminated with alpha-D-glucans.

Kvasinkový (1—>3)-beta-D-glukán sa získává bud z nedezintegrovaných buniek / J. D. MANNERS, A. J. MASSON, J. C. PATTERSON, J. Gen. Microbiol. 80, 411 (1974); A. MISAKI,Yeast (1-> 3) -beta-D-glucan is obtained either from non-disintegrated cells / J. D. MANNERS, A. J. MASSON, J. C. PATTERSON, J. Gen. Microbiol. 80, 411 (1974); A. MISAKI,

J. JOHNSON, S. KIRKWOOD, J. V. SCALETTI, F. SMITH, Carbohydr. Res. 6, 150 (1968); CS 270103/ alebo z dezintegrovaných buniek /CS 243173/, ktoré sa viacnásobne extrahujú zriedenými alkáliami a zriedenými organickými i anorganickými kyselinami, připadne za použitia zmáčadiel. Získaný zvyšok představuje nerozpustný stěnový (1—»3)-beta-D-glukán kvasiniek.J. JOHNSON, S. KIRKWOOD, J.V. SCALETTI, F. SMITH, Carbohydr. Res. 6, 150 (1968); CS 270103) or from disintegrated cells (CS 243173) which are extracted several times with dilute alkali and dilute organic and inorganic acids, optionally using wetting agents. The residue obtained is an insoluble yeast (1 → 3) -beta-D-glucan.

Týmito sposobmi připravený beta-D-glukán máze v niektorých prípadoch - závislých od výběru kmeňa a spSsobu jeho kultivácie - obsahovat' alfa-D-glukány, ktoré v značnéj miere žnižujú jeho imunomodulačnú aktivitu.The beta-D-glucan prepared in this manner may, in some cases - depending on the strain selection and the way in which it is cultivated - contain alpha-D-glucans, which greatly reduce its immunomodulatory activity.

Zistilo sa, že taký polysacharidový preparát, ktorý okrem (1—^3)-beta-D-glukánu obsahuje aj nežiadúci alfa-D-glukán, je možné purifikovať sp&sobom podťa vynálezu. Podstata vynálezu spočívá v tom, že polysacharidový preparát sa tepelne upraví do homogenizovanej formy, ktorou je gél, event. v případe pólysacharidového preparátu, ktorý gél netvoří, vodná suspenzia, přidá sa k němu fosfořečňanový tlmivý roztok a amylolytický enzým. Zistilo sa, že ako amylolytický enzým sa máze použiť čistá alfa-amyláza, Specificky hydrolyzujúca (l->4)-alfa-D-glukány alebo zmes enzýmov (komerčně dostupné technické preparáty) súčastíou ktorej sú připadne enzýmy s beta-amylázovou aktivitou alebo s (1—>3)-alfa-D-glukozidázovou aktivitou. Amylolytický enzým sa pri teplote 25 až 50 *C nechá posobiť až do rozloženia nežiadúcich alfa-D-glukánových příměsí na rozpustné dextriny, ktoré sa odstránia filtráciou reakčnej zmesi a nerozpustný beta-D-glukán sa izoluje, premyje (vodou a organickým rozpúšťadlom) a vysuší. Přítomností, resp. nepřítomností znečistíujúcich polysacharidov (alfa-D-glukány) sa zisťuje IČ připadne ^C-NMR spektroskopiou.It has been found that such a polysaccharide preparation which, in addition to (1 -?) - beta-D-glucan, also contains the undesired alpha-D-glucan, can be purified according to the invention. The present invention is characterized in that the polysaccharide preparation is heat-treated into a homogenized form, which is a gel, optionally a gel. in the case of a non-gel-forming polysaccharide preparation, an aqueous suspension, phosphate buffer and an amylolytic enzyme are added thereto. It has been found that pure alpha-amylase, specifically hydrolyzing (1-> 4) -alpha-D-glucanes or a mixture of enzymes (commercially available technical preparations) may be used as an amylolytic enzyme, optionally including enzymes with beta-amylase activity or (1-> 3) -α-D-glucosidase activity. The amylolytic enzyme is maintained at 25 to 50 ° C until decomposition of undesirable alpha-D-glucan impurities into soluble dextrins, which are removed by filtration of the reaction mixture and the insoluble beta-D-glucan isolated, washed (water and organic solvent) and dried. Presence, respectively. in the absence of polluting polysaccharides (alpha-D-glucans), IR and @ 1 C-NMR spectroscopy were used.

Hlavnou výhodou postupu je špecifické odstránenie znečistí ujúcich alfa-D-glukánov bez atakovania a modifikácie připravovaného (1—»3)-beta-D-glukánu, ktorý v purifikovanej formě má vyššiu imunomodulačnú účinností ako povodný znečistěný (1—*3)-beta-D-glukán.The main advantage of the process is the specific removal of contaminating alpha-D-glucans without attacking and modifying the prepared (1 → 3) -beta-D-glucan, which in purified form has a higher immunomodulatory activity than the flooded (1 → 3) -beta -D-glucan.

Uvedené příklady ilustrujú, ale neobmedzujú predmet vynálezu.These examples illustrate but do not limit the scope of the invention.

Příklad 1Example 1

Získanie kvasinkového (1—>3)-beta-D-glukánuObtaining yeast (1-> 3) -beta-D-glucan

100 g pekárského droždia (Saccharomyces cerevisiae) sa suspenduje v 150 ml 6 % hmot. hydroxidu sodného a pri 60 C sa mieša 4 h. Suspenzia sa zriedi 100 ml 60 C teplej vody a odstředí. Sediment sa suspenduje v 150 ml 3 % hmot. hydroxidu sodného, mieša pri 80 až 100 *C 2 h a odstředí. Sediment sa trikrát premyje vodou a extrahuje trikrát 20 ml 4 S hmot. kyselinou chlorovodíkovou za miešania pri teplote miestnosti 2 h a odstředí. Sediment sa premýva vodou dovtedy, až supernatant je číry a reaguje neutrálně. Získaný stěnový glukán sa lyofilizuje. Výťažok 4,5 až 5,4 % hmot. počítané na sušinu kvasiniek. Glukán neobsahuje dusík a obsah popola je 0,3 až 0,6 % hmot. IČ spektrum obsahovalo okrem absorbčného pásu pri 890 cm“1 charakteristického pre beta-glykozidové vazby aj pásy pri 720 až 725 a 920 až 935 cm1 a v 1^C-NMR spektre boli signály s chemickým posunom 100,9 a 83,2 ppm charakteristické pre (l—>4)-alfa- príp. (1—>3)-alfa-D-glykozidové vazby.100 g of baker's yeast (Saccharomyces cerevisiae) is suspended in 150 ml of 6% by weight. sodium hydroxide and stirred at 60 ° C for 4 h. The suspension is diluted with 100 ml of 60 C warm water and centrifuged. The sediment is suspended in 150 ml of 3 wt. sodium hydroxide, stirred at 80-100 ° C for 2 h and centrifuged. The sediment is washed three times with water and extracted three times with 20 ml of 4 wt. hydrochloric acid with stirring at room temperature for 2 h and centrifuged. The sediment is washed with water until the supernatant is clear and neutral. The obtained wall glucan is lyophilized. Yield 4.5-5.4 wt. calculated on the dry matter of yeast. The glucan does not contain nitrogen and the ash content is 0.3 to 0.6% by weight. The IR spectrum contained, in addition to the absorption band at 890 cm -1 characteristic of beta-glycoside bonds, the bands at 720-725 and 920-935 cm -1 , and in the 1 C-NMR spectrum, chemical shift signals of 100.9 and 83.2 ppm were characteristic for (1-> 4) -alpha- or. (1-> 3) -alpha-D-glycoside bonds.

Příklad 2 g beta-D-glukánu z příkladu 1 sa zahrejú v 100 ml HjO na vriacom vodnom kúpeli tak, aby sa vytvořil gél. Po vychladnutí sa přidá 10 ml fosforečňanového tlmivého roztoku pH = 6,0, obsahujúceho 10 mg alfa-amylázy s pH optimom v oblasti 5,9 až 6,5. Enzým sa nechá pri laboratórnej teplote posobiť 72 h za občasného premiešania.Example 2 g of the beta-D-glucan of Example 1 are heated in 100 ml of H10 on a boiling water bath to form a gel. After cooling, 10 ml of phosphate buffer pH = 6.0 containing 10 mg of alpha-amylase with a pH optimum in the range of 5.9 to 6.5 are added. The enzyme is allowed to stand at room temperature for 72 h with occasional stirring.

Potom sa nerozpustný polysacharid oddělí na frite, trikrát premyje vodou 50 ‘c teplouThen the insoluble polysaccharide is separated on a frit, washed three times with 50 vodou C water

IN"

CS 274030 Bl a acetónom a nechá vysušiť na vzduchu. Výťažok 1,5 g. IČ spektrum produktu nevykazuje absorbčné pásy charakteristické pre alfa-D-glukány.CS 274030 B1 and acetone and allowed to air dry. Yield 1.5 g. The IR spectrum of the product does not show absorption bands characteristic of alpha-D-glucans.

Příklad 3Example 3

Gél polysacharidového preparátu, připravený ako v příklade 2 sa termostatuje na teplotu 35 'C, přidá sa fosforečňanový tlmivý roztok o hodnotě pH 4,5 až 6,5, ktoré vyhovuje pH optimu oboch použitých enzýmov, přidá sa roztok alfa-amylázy a gluko-amylázy v množstve, aby poměr sumy enzýmov ku substrátu bol 1 : 100. Enzýmy sa nechájú posobiť za miešania 2 dni a reakčná zmes sa spracuje ako v příklade 2. IČ spektrum produktu nevykazuje absorbčné pásy charakteristické pre alfa-D-glukány.The gel of the polysaccharide preparation, prepared as in Example 2, is thermostatized to a temperature of 35 ° C, a phosphate buffer of pH 4.5 to 6.5 is added, which satisfies the pH optimum of the two enzymes used, a solution of alpha-amylase and glucose is added. The enzymes were allowed to stir under stirring for 2 days and the reaction mixture was worked up as in Example 2. The IR spectrum of the product did not show the absorption bands characteristic of alpha-D-glucanes.

Přiklad 4Example 4

Claims (2)

Peptidácia polysacharidového preparátu sa uskutoční 3 h miešaním v pufrovanej vodnej suspenzi! o hodnotě pH, ktoré vyhovuje pH optimu použitého enzýmu. Potom sa přidá roztok technického amylázového preparátu (takadiastáza, rohamyláza, bolamyláza) o rovnakom pH ako polysacharidová suspenzia. Po dvojdňovom působení pri 45 ’C sa reakčná zmes ochladí a přefiltruje. Nerozpustný zvyšok sa premyje vodou, metanolom a acetónom. IČ spektrum purifikovaného glukánu nevykazuje absorbčné pásy odpovedajúce alfa-D-glykozidovým vazbám.Peptidation of the polysaccharide preparation is carried out by stirring in a buffered aqueous suspension for 3 h! having a pH value which satisfies the pH optimum of the enzyme used. A solution of the technical amylase preparation (takadiastase, rohamylase, bolamylase) at the same pH as the polysaccharide suspension is then added. After treatment at 45 ° C for 2 days, the reaction mixture is cooled and filtered. The insoluble residue was washed with water, methanol and acetone. The IR spectrum of purified glucan does not show absorption bands corresponding to alpha-D-glycoside bonds. Purifikovaný kvasinkový (1—>3)-beta-D-glukán sa može použiť pri terapii popálenin, dekubitov, nehojacích sa vredov, ako adjuvans a na přípravu Specifických imunostimulačných preparátov.Purified yeast (1-> 3) -beta-D-glucan can be used in the treatment of burns, pressure sores, non-healing ulcers, as adjuvants and for the preparation of Specific Immunostimulatory Preparations. PREDMET VYNÁLEZUOBJECT OF THE INVENTION Spůsob purifikácie kvasinkového (1—>3)-beta-D-glukánu znečistěného alfa-D-glukánmi, vyznačujúci sa tým, že polysacharidový preparát obsahujúci vedl'a (l-> 3)-beta-D-glukánu alfa-D-glukány, tepelne upravený do homogenizovanej formy, sa po přidání fosforečňanového tlmivého roztoku inkubuje pri teplote 25 až 50 c s amylolytickými enzýmami až do rozloženia znečistí ujúcich póly sacharidov na rozpustné dextríny a zo zmesi sa izoluje filtráciou reakčnej zmesi nerozpustný (1-ř3)-beta-D-glukán v purifikovanej formě.Method for purifying yeast (1 → 3) -beta-D-glucan contaminated with alpha-D-glucanes, characterized in that the polysaccharide preparation containing besides (1-> 3) -beta-D-glucan alpha-D-glucanes , heat-treated to a homogenized form, after addition of phosphate buffer is incubated at 25 to 50 ° C with amylolytic enzymes until the pollutant pollutants are decomposed into soluble dextrins and the insoluble (1-β) -beta-D is isolated from the mixture by filtration -glucan in purified form.
CS3889A 1989-01-02 1989-01-02 Method of yeast /1-3/-beta-d-glucan purification CS274030B1 (en)

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