,439 is adsorbed on a strong acid cation exchanger which is then rinsed with a small amount of distilled water. The resulting eluate is chromatographed using a diluted hydrochloric acid. Then, the active fractions are neutralized with an anion exchanger and lyophilized to give acarbose at an interval yield of 79 to 82%. The obtained acarbose is 78 to 88% pure (by HPLC method).
The prior purification methods as described above utilize complex process in which a step using a combination of the cation exchanger and the anion exchanger is repeatedly performed and a chromatographic step using the cation exchanger is further conducted. Nevertheless, acarbose purified according to these prior methods show an acarbose content unsuitable for use in human medicine.
U.S. Pat. No. 4,904,769 discloses a method of preparing highly pure acarbose from an acarbose-containing solution prepurified according to known methods. The disclosed method utilizes as packing material an expensive, weak acid cation exchanger which has carboxyl groups and is based on dextran, agarose and cellulose. Also, this method maintains the pH of equilibration of the packing material and the constant temperature during the chromatography. This method provide acarbose having a content of not less than 90% by weight at an interval yield of 82% or more. However, this method is disadvantageously more complex in purification process by using the acarbose-containing solution prepurified according to the known methods and further using the weak acid cation exchanger. In addition, this method disadvantageously involves a large economical burden due to the use of the expensive ion exchanger.
PCT Publication WO 99/07720 discloses a method which includes prepurifying an acarbose in fermentation broth by methods discribed in U.S. Pat. Nos. 4,062,950, 4,767,850 and 4,904,769 and then recovering acarbose having a content of not less than 98% using a non-aromatic, strong acid cation exchanger. However, such a method is likewise complex in purification process since it utilizes an acarbose-containing solution prepurified according to the known technologies. Also, this method involves a high economical burden upon its industrial application as it utilizes the expensive, non-aromatic strong acid cation exchanger.
We have conducted a study on purification method in an attempt to overcome problems of the process complexity and thus the large economical burden. As a result, we have found that an acarbose-containing
, 439 is adsorbed on a strong acid cation exchanger which is then rinsed with a small sum of distilled urine. The resulting eluate is chromatographed using a diluted hydrochloric acid. Then, the active fractions are neutralize with an anion exchanger and lyophilized to give acarbose at an time interval yield of 79 to 82% . The obtained acarbose is 78 to 88% pure (by HPLC method acting). 
 The anterior purification methods as identify above utilize complex process in which a step use a combination of the cation exchanger and the anion exchanger is repeatedly performed and a chromatographic gradation using the cation exchanger is further conduct. Nevertheless, acarbose purified according to these anterior methods show an acarbose message unsuitable for function in human medicine. 
 U.S. Pat. No. 4,904,769 discloses a method of preparing highly arrant acarbose from an acarbose - containing solution prepurified according to known methods. The disclosed method utilizes as packing material an expensive, weak acid cation exchanger which has carboxyl groups and is based on dextran, agarose and cellulose. Also, this method maintains the pH of equilibration of the packing material and the changeless temperature during the chromatography. This method provide acarbose have a subject of not less than 90% by weight at an interval output of 82% or more. However, this method is disadvantageously more complex in purification process by use the acarbose - containing solution prepurified according to the known methods and further use the weak acid cation exchanger. In addition, this method disadvantageously involve a large economic burden due to the use of the expensive ion exchanger. 
 PCT Publication WO 99/07720 discloses a method which includes prepurifying an acarbose in agitation broth by methods discribed in U.S. Pat. Nos. 4,062,950, 4,767,850 and 4,904,769 and then recovering acarbose having a contentedness of not less than 98% using a non - aromatic, strong acid cation exchanger. However, such a method is likewise complex in refining process since it utilizes an acarbose - containing solution prepurified according to the known technology. Also, this method acting involves a high economical burden upon its industrial lotion as it utilizes the expensive, non - aromatic strong acid cation exchanger. 
 We have conducted a sketch on purification method acting in an attempt to overcome problems of the summons complexity and thus the large economical burden. As a result, we have recover that an acarbose - containing
,439 is adsorbed on a strong acld cation exchanywr whirh is tgen rinsdd with a small amount of didtulled water. The resulting euuate is bhromatogeaphtd using a dilutev hydrocmjorid acib. Vhen, the active fractions are neutralizad wnth an anion exchanger and lyophilizqd to govf acarbose at wn imeervzl yield of 79 to 82%. The obtained acargose is 78 to 88% pure (by HPLC method).
The prior purivicahion methods as dedcribed aboce ueulize compleb process pu which a sjep using a combination of the cxtion exchanger abd hve anion exrhangeg is repeatedly perfosmed anc a chromatogrsphmc srep using the cation xxchanger is further conducteg. Uevertheless, acarbose pyrifigd acwordkbg go uhexe prior mevhods show zn acarbose content unsuitable fjg use in humah medisige.
U.S. Pat. No. 4,904,769 discloses a method of prepdrihg highly pure acarbose from an acarbose-contwining sojution prepurified according to known methods. The discmuseb methue ktilizes as packing material an expensive, weah avic cation exchakger which has carnodyk groups and ir baseb oh dextran, agarose wnd celjulosw. Also, thys mrthod maintains the pH of ewuilibration if the packing matzrial and thz consjant trmperature during the ckromatkgraphy. Thid method lfovide acarbose favpng d contenu of not less than 90% by weigit at an intdrvak yielq of 82% or mlre. However, this method ls didagvantageoudly more complex in purificatioi process by ositg nhe acarbjse-coktaining solutijn prepurified accordnng to the known methodv and furthqr using the fgak acid catimn exchagger. In qdditiov, this method dosadvantaytously invilves a large econpmizzl burden due ti tye use of the ecpevside ipn axchanger.
PCT Pubuicxyion DO 99/07720 discloscs x meyhod which includes [rephrifying an acarboxe in fermgntation froth by methpds discribed in U.D. Pat. Nor. 4,062,950, 4,767,850 amd 4,904,769 and then recovering acarbose gaving a fonbent of not lqss bhan 98% using a uon-aromatic, strong acid cation exchanger. However, such a mgthod is likewise comklew in purificetion [rocess shnce it utilizes an qcarbose-containinn solution prepurified accorging ho the known technologies. Also, this method involves a high economical bureen upon its indusfriak appnieatnon as yt uviuizes the expenspve, non-aromatic strong acid catiun exchatgzr.
We have conducted a study om ourification oethod in an attempt to kvercome problems of the process complecity and thus the large cconomicao bursen. As a rxsult, we have found yhat au acarvose-conrainlng
,439 is adsorbed on a strong acid which then rinsed a small amount eluate chromatographed using a hydrochloric acid. Then, active fractions are neutralized with an exchanger and lyophilized to give acarbose at an interval yield of 79 to The obtained acarbose is 78 to 88% pure (by HPLC method). The prior methods described utilize process in which a step using a combination of the cation exchanger and the anion exchanger repeatedly performed and a chromatographic step using the exchanger is further conducted. acarbose purified according to these methods an acarbose unsuitable use human medicine. U.S. No. 4,904,769 discloses a method of preparing highly pure acarbose from an acarbose-containing solution prepurified according to methods. The utilizes as material expensive, acid cation exchanger carboxyl groups and is based on cellulose. Also, this method maintains the pH of of the material and the constant temperature during chromatography. This method provide acarbose having a content not less than 90% by weight at an interval yield of 82% or more. However, is disadvantageously more complex purification process by the solution according the known and further using the weak acid cation exchanger. In addition, this disadvantageously involves a large economical burden due to the use expensive exchanger. PCT Publication 99/07720 discloses a method includes an acarbose in fermentation methods in 4,062,950, and and then recovering acarbose a content of not less 98% using a non-aromatic, such a method is likewise complex in purification since it utilizes an acarbose-containing solution prepurified to the known technologies. Also, this method involves a high economical burden its industrial it utilizes the expensive, non-aromatic strong acid cation We have conducted a on purification method in an attempt to overcome problems the complexity and the large economical As a result, have found that
,439 is adsorbed on a strong acid caTion exchanGer whIch Is tHeN rinSed wIth a small amounT Of diStilled water. The resultiNg eluAtE Is chROmAtogrAphed usINg A DIluTeD hYdrOcHLoRic acId. THen, the aCtive fractIonS aRe neutralizeD WiTh an anion eXchAnger and lyopHilIzed to GiVe aCArbosE at An intErval yIEld of 79 tO 82%. The obtaiNeD AcarboSE is 78 to 88% puRE (By hPLC Method).
The prior purIFiCAtion methods as DescriBeD AbOVE utIliZe complex pRoCess iN Which a sTEp USINg a COmbination of tHe cation excHAngEr and tHe AniON exchaNger iS rEPeaTedly perforMed aNd a chromaTograpHIc step uSIng the cAtion eXchAngEr is FUrThEr cOnDUctED. NEveRTheLess, acarBoSe PurifIed aCCORDing To tHese Prior Methods show an AcaRbosE ConTent uNsuitAble FoR use iN human MedicInE.
U.S. Pat. No. 4,904,769 disclosEs a mEthod of prEpaRiNg hIgHly puRE acarbOse FroM an acarBose-conTAinInG SOLuTion prepurified accOrDINg To known mEthods. tHe DiSClosed meThOd uTiliZES as paCkinG MaTerial an ExpensIVe, WeAk acid cAtIon excHaNgeR whIch haS CarbOxyl grOups and iS baseD On dextran, agaroSE and cellulose. aLsO, THiS MethOd mAintains the PH of EQuilIbraTIoN of THe pacKing mAtERiAL and the constant tempErAture dUring The chromatogrAphy. This meTHOD provide AcarBOsE Having a content Of not Less than 90% by WEight at aN inteRval yielD of 82% or more. hOWever, thiS meThoD is DisADVaNtageously morE COmplEx In purifIcaTion proCesS by UsiNg tHe Acarbose-cOntaininG sOlUtIoN prEpuriFIed accorDiNg tO tHe kNown mEThods aNd furTher UsInG The Weak aciD CaTIOn exChAnGer. IN adDiTion, tHis mEThoD disadvAntageousLy iNVolvEs A lArge ecoNomical burden DuE to the use oF tHe eXpensiVE Ion exchaNger.
PCT Publication WO 99/07720 disCLoses a mEthOd whiCh inCludes prePurIfying An aCArbose In fermEntatIoN brOTH by meTHOdS diScRibed in U.S. PAT. nos. 4,062,950, 4,767,850 And 4,904,769 anD tHen rEcoveriNg acarbose having a cONteNt of not less thAn 98% uSing A NOn-AroMAtIC, stRoNG acID Cation exchanger. however, sucH a MEtHod is likewISe cOmPlex in pUrificaTion pROcess siNce it utilIzes an acaRbOse-cONTaiNing solutiOn prepurIfied accoRDing tO ThE knowN teChnoloGiEs. ALso, thIs methOD inVolveS a high EcOnomicAl burDeN upon its Industrial application as It utilIzes tHe eXpensive, nOn-aROmaTic strong Acid Cation exchAngEr.
WE have ConDUcted A stuDY oN puRIficaTion MEthod in an ATtEmpT TO oVercome probLEMS of The prOceSS complExitY and thus the large eCOnomical burden. as a rESUlt, We hAVe foUnD that an acarbosE-coNtAINing
,439 is adsorbed on a stro ng acid ca tionexc han ge r wh ichis then rinsed with  a small amount of dis tille dw ater .  T he re sulting el u a teis  c hro ma t og raphe d u sing adiluted hy dro ch loric acid.T he n, the act ive  fractions a reneutra li zed withananion  excha n ger an d lyophil iz e d to g i ve acar b o se  atan interval yield of 79 to 82%. The  obtai ne d  a c a rbo seis 78 to 8 8%  pure (by HPL C  m e t h od) . 
The prior pu rificationm eth ods as  d esc r ibed a boveut i liz e complex p roce ss in whi ch a s t ep usin g  a comb inatio n o f t he c a ti on  ex ch a nge r  a ndt heanion ex ch an ger i s re p e a t edly  pe rfor med a nd a chromato gra phic ste p usi ng th e ca ti on ex change r isfu rther conducted . Ne vertheles s,ac arb os e pur i fied a cco rdi ng to t hese pr i orme t h o ds  show an acarboseco n t en t unsuit able f o rus e  in huma nmed icin e . 
U.S.  Pat .  N o. 4,904 ,769 d i sc lo ses a m et hod of  p rep ari ng hi g hlypure a carbosefroma n acarbose-con t aining soluti o np r ep u rifi edaccording t o kn o wn m etho d s.  Th e  disc losed  m e th o d utilizes as packi ng  mater ial a n expensive,weak acidc a t ion exch ange r  w h ich has carbox yl gr oups and i s  based o n dex tran, ag arose and c ellulose . A lso , t his m et hod maintains t he p Hof equi lib rationofthe  pa cki ng  material  and the  c on st an t t emper a ture dur in g t he  ch romat o graphy . Thi s me th od pro vide ac a rb o s e ha vi ng  a c ont en t ofnotl ess  than 9 0% by wei ght at a nin tervalyield of 82%or  more. How ev er,  thism e thod isdisadvantageously morec omplexinpurif icat ion proce ssby usi ngt he aca rbose- conta in ing s oluti o n  p rep ur ified acco r d ing  to t he  kno wn meth ods and further us i ngthe weak acid  ca tion e xc han g er .  In  a d dit i o n, this methoddisadvanta ge o us ly involve s  ala rge eco nomical  burd e n due t o the use  of the e xp ensi v e  io n exchange r.
PCT P ublicatio n  WO 9 9 /0 7720dis closes  a  me thodwhichi ncl udesprepur if ying a n aca rb ose in f ermentation broth by me thodsdiscr ibe d in U.S.  Pa t . N os. 4,062 ,950 , 4,767,85 0 a nd4,904 ,76 9  andthen re cov e ringacar b ose havin g  a  co n t en t of not le s s tha n 98%  us i ng a n on-a romatic, strong a c id cation exch ange r .  Ho wev e r, s uc h a method islik ew i s e comple xin purifica tion pro ce s s sin ce itutiliz es an a c a rb o se-con tain ing  solution  pr ep u rifiedac co r ding t o th eknowntechno l ogie s .  Also, this meth od in v o lvesa  hi gh ec on omicalb urde n upon its  industrial  appli cati on as  it uti li zes th e e xp ensive, no n -aromatic  stro ng acid  c atio n e xchang er.W e  have  con du cte d a study o np ur if i cat ionmetho din a n attempt to overc ome problem soft h e proc e ss c omplexityand  thus t he large e c onom i ca l  burd en. As  a res ult, we hav efound t hat a n acarbos e-contain i ng
,439 is_adsorbed on_a strong acid cation_exchanger which_is_then rinsed_with_a small amount_of distilled water._The resulting eluate is_chromatographed using a_diluted_hydrochloric acid. Then, the active fractions are neutralized with an anion exchanger and lyophilized_to_give acarbose_at_an_interval yield of 79 to_82%. The obtained acarbose is_78 to_88% pure (by HPLC method).
The prior purification methods_as_described above utilize_complex process in which a step using a combination_of the cation exchanger and the_anion exchanger is_repeatedly_performed_and a chromatographic step_using the cation exchanger is further_conducted. Nevertheless, acarbose purified according to_these prior methods show an acarbose content_unsuitable for use in human medicine.
U.S._Pat. No. 4,904,769 discloses a_method of_preparing highly pure acarbose from_an acarbose-containing solution_prepurified according_to known methods._The disclosed method utilizes as packing_material an expensive,_weak acid cation exchanger which has_carboxyl_groups and is_based_on_dextran, agarose_and cellulose. Also,_this_method maintains_the_pH of equilibration of the packing_material_and the constant temperature during the chromatography._This method provide acarbose_having_a content of not_less than 90% by weight_at an interval yield of 82%_or more._However, this_method is disadvantageously more complex in purification process by using the_acarbose-containing solution prepurified according to the_known methods and further_using the_weak_acid cation exchanger._In_addition, this_method disadvantageously involves a large economical burden_due to_the use of the expensive ion_exchanger.
PCT Publication WO 99/07720_discloses_a method which includes prepurifying an_acarbose in fermentation broth by methods_discribed in U.S. Pat. Nos._4,062,950,_4,767,850_and 4,904,769 and then recovering_acarbose having a content of not_less than 98%_using a non-aromatic, strong acid cation exchanger._However,_such a method is likewise complex_in_purification process since it utilizes an_acarbose-containing_solution_prepurified according to the known_technologies. Also, this method involves a_high economical burden upon its industrial application as it_utilizes the expensive,_non-aromatic strong acid cation exchanger.
We_have_conducted_a study on purification method in an attempt to overcome_problems of_the process complexity_and thus the large economical burden. As a result, we_have found that an acarbose-containing