ES2108572T3 - Procedimiento para el aislamiento de acido clavulanico y de sales farmaceuticamente aceptables de este a partir del caldo de fermentacion de streptomyces sp p 6621 ferm p 2804. - Google Patents

Procedimiento para el aislamiento de acido clavulanico y de sales farmaceuticamente aceptables de este a partir del caldo de fermentacion de streptomyces sp p 6621 ferm p 2804.

Info

Publication number
ES2108572T3
ES2108572T3 ES95909194T ES95909194T ES2108572T3 ES 2108572 T3 ES2108572 T3 ES 2108572T3 ES 95909194 T ES95909194 T ES 95909194T ES 95909194 T ES95909194 T ES 95909194T ES 2108572 T3 ES2108572 T3 ES 2108572T3
Authority
ES
Spain
Prior art keywords
clavulanic acid
isolation
pharmaceutically acceptable
acceptable salts
fermentation broth
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired - Lifetime
Application number
ES95909194T
Other languages
English (en)
Inventor
Egidij Capuder
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Lek Pharmaceuticals dd
Original Assignee
Lek Pharmaceuticals and Chemical Co dd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=20431337&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=ES2108572(T3) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Lek Pharmaceuticals and Chemical Co dd filed Critical Lek Pharmaceuticals and Chemical Co dd
Application granted granted Critical
Publication of ES2108572T3 publication Critical patent/ES2108572T3/es
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
    • C12P17/00—Preparation of heterocyclic carbon compounds with only O, N, S, Se or Te as ring hetero atoms
    • C12P17/18—Preparation of heterocyclic carbon compounds with only O, N, S, Se or Te as ring hetero atoms containing at least two hetero rings condensed among themselves or condensed with a common carbocyclic ring system, e.g. rifamycin
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
    • C12P17/00—Preparation of heterocyclic carbon compounds with only O, N, S, Se or Te as ring hetero atoms
    • C12P17/18—Preparation of heterocyclic carbon compounds with only O, N, S, Se or Te as ring hetero atoms containing at least two hetero rings condensed among themselves or condensed with a common carbocyclic ring system, e.g. rifamycin
    • C12P17/188—Heterocyclic compound containing in the condensed system at least one hetero ring having nitrogen atoms and oxygen atoms as the only ring heteroatoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D503/00—Heterocyclic compounds containing 4-oxa-1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula:, e.g. oxapenicillins, clavulanic acid derivatives; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulfur-containing hetero ring
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N1/00—Microorganisms, e.g. protozoa; Compositions thereof; Processes of propagating, maintaining or preserving microorganisms or compositions thereof; Processes of preparing or isolating a composition containing a microorganism; Culture media therefor
    • C12N1/02—Separating microorganisms from their culture media
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10S435/00—Chemistry: molecular biology and microbiology
    • Y10S435/8215—Microorganisms
    • Y10S435/822—Microorganisms using bacteria or actinomycetales
    • Y10S435/886—Streptomyces

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • Health & Medical Sciences (AREA)
  • Biotechnology (AREA)
  • Genetics & Genomics (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Microbiology (AREA)
  • Biochemistry (AREA)
  • General Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • Medicinal Chemistry (AREA)
  • Virology (AREA)
  • Biomedical Technology (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
  • Seasonings (AREA)

Abstract

SE HA DESCUBIERTO UN PROCESO NUEVO Y MEJORADO PARA EL AISLAMIENTO DE ACIDO CLAVULANICO Y SALES FARMACEUTICAMENTE ACEPTABLES DEL MISMO COMO CLAVULANATO POTASICO A PARTIR DEL CALDO DE CULTIVO DE FERMENTACION ACUOSA DE ESTREPTOMICES SP P 6621 FERM P 2804, EN DONDE A PARTIR DEL CALDO DE CULTIVO DE FERMENTACION ACUOSA EL MICELIUM, UNA MAYOR PARTE DE LAS PROTEINAS Y DE OTRAS PARTICULAS SOLIDAS SUSPENDIDAS SON ELIMINADAS POR MICROFILTRACION EN UN VALOR DE PH DEL MEDIO ENTRE 5.8 Y 6.2 Y A UNA TEMPERATURA ENTRE APROX. 20 ADO (LA FASE ACUOSA) ES OPCIONAL Y ADICIONALMENTE PURIFICADO POR ULTRAFILTRACION, Y EL CALDO DE CULTIVO PURIFICADO DE ESTA MANERA ES CONCENTRADO POR OSMOSIS INVERSA, DESPUES ES DIRECTAMENTE EXTRAIDO EN UNA CONTRACORRIENTE EN EXTRACTORES CENTRIFUGOS CON UN DISOLVENTE ORGANICO INMISCIBLE EN AGUA EN UN VALOR DE PH DEL MEDIO ENTRE 1 Y 3, CON LO CUAL LAS PROTEINAS TODAVIA RESTANTES SON ELIMINADAS SIMULTANEAMENTE, DE LA FASE ORGANICA OBTENIDA LAS IMPUREZAS SOLUBLES EN AGUA SON ELIMINADASLAVANDO LA FASE ORGANICA CON AGUA, LA FASE ORGANICA ES SECADA IN VACUO EN UNA COLUMNA DE RECTIFICACION PARA UN CONTENIDO EN AGUA INFERIOR A UN 0.1 % VOL. Y DESPUES CONCENTRADA POR EVAPORACION, DESCOLORADA POR UN TRATAMIENTO CON CARBONO ACTIVO, Y DESPUES EL ACIDO CLAVULANICO PRESENTE EN LA FASE ORGANICA SECA, MAS CORRECTAMENTE EN LA FASE DE ACETATO DE ETILO, ES AISLADO Y PURIFICADO POR UNA REACCION CON N,N''-DIISOPROPILETILENDIAMINA A UNA TEMPERATURA DE APROX. TEMPERATURA AMBIENTE PARA EL INTERMEDIARIO DICLAVULANATO DE N,N''DIISOPROPILETILENODIAMONICO QUE ES AISLADO Y DESPUES REACCIONANDO CON HEXANOATO 2-ETILO POTASICO EN ISOPROPANOL PARA PRODUCIR LA SAL POTASICA DEL ACIDO CLAVULANICO QUE TENGA ALTA PUREZA
ES95909194T 1994-03-02 1995-02-23 Procedimiento para el aislamiento de acido clavulanico y de sales farmaceuticamente aceptables de este a partir del caldo de fermentacion de streptomyces sp p 6621 ferm p 2804. Expired - Lifetime ES2108572T3 (es)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
SI9400107A SI9400107A (en) 1994-03-02 1994-03-02 New process of the isolation of clavulanic acid and its pharmaceutical salts from fermented broth of streptomyces sp.p 6621 ferm p 2804.

Publications (1)

Publication Number Publication Date
ES2108572T3 true ES2108572T3 (es) 1997-12-16

Family

ID=20431337

Family Applications (1)

Application Number Title Priority Date Filing Date
ES95909194T Expired - Lifetime ES2108572T3 (es) 1994-03-02 1995-02-23 Procedimiento para el aislamiento de acido clavulanico y de sales farmaceuticamente aceptables de este a partir del caldo de fermentacion de streptomyces sp p 6621 ferm p 2804.

Country Status (25)

Country Link
US (4) US5780274A (es)
EP (1) EP0748387B1 (es)
JP (1) JP2948661B2 (es)
KR (1) KR100293172B1 (es)
CN (1) CN1055694C (es)
AT (1) ATE159549T1 (es)
AU (1) AU694176B2 (es)
BG (1) BG62213B1 (es)
CA (1) CA2184619A1 (es)
CZ (1) CZ284117B6 (es)
DE (1) DE69500925T2 (es)
DK (1) DK0748387T3 (es)
ES (1) ES2108572T3 (es)
FI (1) FI963408A (es)
GR (1) GR3025942T3 (es)
HU (1) HUT74944A (es)
NO (1) NO318374B1 (es)
NZ (1) NZ279958A (es)
PL (1) PL180520B1 (es)
RO (1) RO118760B1 (es)
RU (1) RU2206613C2 (es)
SI (1) SI9400107A (es)
SK (1) SK279780B6 (es)
WO (1) WO1995023870A1 (es)
ZA (1) ZA951689B (es)

Families Citing this family (21)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AT400033B (de) 1992-03-10 1995-09-25 Biochemie Gmbh Neues verfahren zur isolierung und reinigung von clavulansäure und zur herstellung von pharmakologisch verträglichen salzen derselben
SI9400107A (en) * 1994-03-02 1995-10-31 Lek Tovarna Farmacevtskih New process of the isolation of clavulanic acid and its pharmaceutical salts from fermented broth of streptomyces sp.p 6621 ferm p 2804.
GB9500977D0 (en) 1995-01-19 1995-03-08 Smithkline Beecham Plc Novel process
SI9500074A (en) † 1995-03-10 1996-10-31 Lek Tovarna Farmacevtskih Process for preparation of alkani salts of clavulanic acid.
SI9500134B (sl) * 1995-04-20 2004-04-30 Lek, Postopek za pripravo čistih alkalijskih soli klavulanske kisline
GB9515809D0 (en) * 1995-08-02 1995-10-04 Smithkline Beecham Plc Process
SI9500265A1 (en) 1995-08-28 1997-02-28 Lek Tovarna Farmacevtskih Process for purification of the aqueous fermented broth filtrate of streptomyces sp. p 6621 ferm p 2804 by ultrafiltration
AT403375B (de) * 1995-11-15 1998-01-26 Biochemie Gmbh Verfahren zur fällung von alkalisalzen der clavulansäure
US6414142B1 (en) * 1996-06-13 2002-07-02 Smithkline Beecham Corporation Process for preparing potassium clavulanate
AU5551698A (en) * 1996-11-11 1998-06-03 Gist-Brocades B.V. Process for the preparation of salts and esters of clavulanic acid
AT404728B (de) * 1996-11-27 1999-02-25 Biochemie Gmbh Verfahren zur herstellung von clavulansäure-aminsalzen
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DZ2456A1 (fr) * 1997-04-04 2003-01-18 Smithkline Beecham Plc Procédé de préparation de sels de l'acide clavulanique.
US6979735B1 (en) * 1999-04-01 2005-12-27 Dsm N.V. Agglomerates by crystallization
KR100827898B1 (ko) 2000-05-13 2008-05-07 스미스클라인비이참피이엘시이 클라불란산의 염의 정제 방법
GB0022841D0 (en) * 2000-09-18 2000-11-01 Smithkline Beecham Plc Process
KR100443082B1 (ko) * 2002-10-18 2004-08-04 삼성전자주식회사 반도체 장치의 트랜지스터 제조 방법
KR100768476B1 (ko) 2005-11-24 2007-10-18 한국해양연구원 항암물질을 생산하는 방선균 스트렙토마이세스 속 균주,이의 분리방법, 이로부터 반고형 추출물을 제조하는 방법,이로부터 유래한 반고형 추출물 및 이를 이용한 항암제조성물
CN102838624B (zh) * 2012-09-07 2014-10-29 安徽普朗膜技术有限公司 一种从发酵液中纯化克拉维酸的方法
CN104910194A (zh) * 2015-05-28 2015-09-16 高希章 一种克拉维酸钾的制备方法及其复方制剂

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Also Published As

Publication number Publication date
NO963628L (no) 1996-10-17
DK0748387T3 (da) 1998-05-25
WO1995023870A1 (en) 1995-09-08
KR100293172B1 (ko) 2001-06-15
PL180520B1 (pl) 2001-02-28
SK279780B6 (sk) 1999-03-12
SI9400107A (en) 1995-10-31
BG62213B1 (bg) 1999-05-31
US6566106B2 (en) 2003-05-20
NO318374B1 (no) 2005-03-14
CN1143388A (zh) 1997-02-19
AU1724195A (en) 1995-09-18
SK112096A3 (en) 1997-02-05
CZ255796A3 (en) 1996-12-11
AU694176B2 (en) 1998-07-16
HUT74944A (en) 1997-03-28
PL316085A1 (en) 1996-12-23
NZ279958A (en) 1997-04-24
EP0748387A1 (en) 1996-12-18
GR3025942T3 (en) 1998-04-30
RU2206613C2 (ru) 2003-06-20
HU9602351D0 (en) 1996-10-28
US20010007761A1 (en) 2001-07-12
FI963408A (fi) 1996-10-30
KR970701786A (ko) 1997-04-12
ZA951689B (en) 1995-12-11
DE69500925T2 (de) 1998-02-12
CN1055694C (zh) 2000-08-23
NO963628D0 (no) 1996-08-30
FI963408A0 (fi) 1996-09-02
BG100816A (en) 1997-10-31
JPH09504702A (ja) 1997-05-13
US5985625A (en) 1999-11-16
CA2184619A1 (en) 1995-09-08
ATE159549T1 (de) 1997-11-15
US5780274A (en) 1998-07-14
EP0748387B1 (en) 1997-10-22
JP2948661B2 (ja) 1999-09-13
US6207428B1 (en) 2001-03-27
RO118760B1 (ro) 2003-10-30
DE69500925D1 (de) 1997-11-27
CZ284117B6 (cs) 1998-08-12

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