KR970701786A - 스트렙토마이세스 sp. P 6621 FERM P 2804의 발효액으로부터 클라불란산과 제약학적으로 허용가능한 이들의 염을 단리하는 신규한 방법(NOVEL PROCESS FOR THE ISOLATION OF CLAVULANIC ACID AND OF PHARMACEUTICALLY ACCEPTABLE SALTS THEREOF FROM THE FERMENTATION BROTH OF STREPTOMYCES SP. P 6621 FERM P 2804) - Google Patents

스트렙토마이세스 sp. P 6621 FERM P 2804의 발효액으로부터 클라불란산과 제약학적으로 허용가능한 이들의 염을 단리하는 신규한 방법(NOVEL PROCESS FOR THE ISOLATION OF CLAVULANIC ACID AND OF PHARMACEUTICALLY ACCEPTABLE SALTS THEREOF FROM THE FERMENTATION BROTH OF STREPTOMYCES SP. P 6621 FERM P 2804)

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KR970701786A
KR970701786A KR1019960704806A KR19960704806A KR970701786A KR 970701786 A KR970701786 A KR 970701786A KR 1019960704806 A KR1019960704806 A KR 1019960704806A KR 19960704806 A KR19960704806 A KR 19960704806A KR 970701786 A KR970701786 A KR 970701786A
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streptomyces
fermentation broth
clavulanic acid
pharmaceutically acceptable
ferm
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KR100293172B1 (ko
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에지디즈 카푸더
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잔코 즈미텍
레크, 토바나 파마세브츠키 인 케미크니 이즈델코브, 디.디.
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    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12PFERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
    • C12P17/00Preparation of heterocyclic carbon compounds with only O, N, S, Se or Te as ring hetero atoms
    • C12P17/18Preparation 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
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12PFERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
    • C12P17/00Preparation of heterocyclic carbon compounds with only O, N, S, Se or Te as ring hetero atoms
    • C12P17/18Preparation 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
    • C12P17/188Heterocyclic compound containing in the condensed system at least one hetero ring having nitrogen atoms and oxygen atoms as the only ring heteroatoms
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D503/00Heterocyclic 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
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    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N1/00Microorganisms, 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
    • C12N1/02Separating microorganisms from their culture media
    • YGENERAL 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
    • Y10TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10STECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10S435/00Chemistry: molecular biology and microbiology
    • Y10S435/8215Microorganisms
    • Y10S435/822Microorganisms using bacteria or actinomycetales
    • Y10S435/886Streptomyces

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  • 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)
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Abstract

본 발명은 발효액으로부터 대부분의 균사, 단백질 및 다른 부유하는 고체 입자들을 약 20 내지 40℃ 사이에서 pH가 5.8 내지 6.2인 배지에서 미세 여과에 의해 제거하고, 정제된 액(수성층)을 임의로 한외 여과법에 의해 재차 정체한 후 이 정제된 액을 역삼투에 의해 농축하고, 이어서 pH가 1 내지 3인 배지에서 물에 섞이지 않은 유기 용매로 원심분리 추출기 내에서 역류로 직접 추출하여 여전히 남아있는 단백질을 동시에 제거하고, 얻어진 유기층으로부터 유기층을 물로 세척함으로써 수용성 불순물을 제거하고, 상기 유기층은 정유관에서 진공하에서 0.1부피% 이하의 수분 함량으로 건조하고, 증발에 의해 농축하고, 활성탄으로 처리하여 탈색한 후 건조된 유기층에 존재하는 클라불란산을 가장 적당하게 에틸 아세테이트상에서 단리하고 실온 정도에서 N,N'-디이소프로필에틸렌디아민과 반응시켜 중간 단계의 N,N'-디이소프로필에틸렌디암모늄 디클라불라네이트로 정제하고, 이것을 단리하여 칼륨 2-에틸 헥사노에이트의 이소프로판을 용액과 반응시켜 고순도의 클라불란산 칼륨염을 얻는 것을 특징으로 하느 스트렙토마이세스 sp. P 6621 FERM P 2804의 수성 발효액으로부터 클라불란산과 제약학적으로 허용가능한 이들의 염을 단리하는 방법에 관한 신규하고 개선된 방법에 관한 것이다.

Description

스트렙토마이세스 sp. P 6621 FERM P 2804의 발효액으로부터 클라불란산과 제약학적으로 허용가능한 이들의 염을 단리하는 신규한 방법 (NOVEL PROCESS FOR THE ISOLATION OF CLAVULANIC ACID AND OF PHARMACEUTICALLY ACCEPTABLE SALTS THEREOF FORM THE FERMENTATION BROTH OF STREPTOMYCES SP. P 6621 FERM P 2804)
본 내용은 요부공개 건이므로 전문내용을 수록하지 않았음

Claims (5)

  1. 발효액으로부터 대부분의 균사, 단백질 및 다른 부유하는 고체 입자들을 약 20 내지 40℃ 사이에서 pH가 5.8 내지 6.2인 배지에서 미세 여과에 의해 제거하고, 정제된 액(수성층)을 임의로 한외 여과법에 의해 재차 정제한 후, 이 정제된 액을 역삼투에 의해 농축하고, 이어서 pH가 1 내지 3인 배지에서 물에 섞이지 않는 유기 용매로 일련의 원심분리 추출기로 역류로 직접 추출하여 여전히 남아있는 분리된 단백질을 동시에 제거하고, 유기층을 물로 세척하고, 정유관에서 진공 하에서 0.1부피% 이하의 수분 함량으로 건조하고, 증발에 의해 농축하고, 활성탄으로 처리하여 탈색한 후 완전히 건조된 유기층에 존재하는 클라불란산을 단리하고 실온 정도에서 N,N'-디이소프로필에틸렌디아민과 반응시켜 N,N'-디이소프로필에틸렌디암모늄 디클라불라네이트로 정제하고, 이것을 단리하여 칼륨 2-에틸 헥사노에이트의 이소프로판을 용액과 반응시켜 고순도의 클라불란산 칼륨염을 얻는 것을 특징으로 하는 스트렙토마이세스 sp. P 6621 FERM P 2804의 수성 발효액으로부터 클라불란산과 제약학적으로 허용가능한 이들의 염을 단리하는 방법.
  2. 제1항에 있어서, 배지의 pH가 황산으로 조절되는 것을 특징으로 하는 스트렙토마이세스 sp. P 6621 FERM P 2804의 수성 발효액으로부터 클라불란산과 제약학적으로 허용가능한 이들의 염을 단리하는 방법.
  3. 제1항에 있어서, 직접 추출시 물에 섞이지 않는 유기 용매로 에틸아세테이트가 사용되는 것을 특징으로 하는 스트렙토마이세스 sp. P 6621 FERM P 2804의 수성 발효액으로부터 클라불란산과 제약학적으로 허용가능한 이들의 염을 단리하는 방법.
  4. 제1항에 있어서, 정제된 수성 발효액의 직접 역류추출이 15 내지 25℃ 사이에서 에틸 아세테이트로 실시되는 것을 특징으로 하는 스트렙토마이세스 sp. P 6621 FERM P 2804의 수성 발효액으로부터 클라불란산과 제약학적으로 허용가능한 이들의 염을 단리하는 방법.
  5. 제1항에 있어서, 유기층의 건조에서 수분 함량이 0.03 내지 0.05부피%인 것을 특징으로 하는 스트렙토마이세스 sp. P 6621 FERM P 2804의 수성 발효액으로부터 클라불란산과 제약학적으로 허용가능한 이들의 염을 단리하는 방법.
    ※ 참고사항 : 최초출원 내용에 의하여 공개하는 것임.
KR1019960704806A 1994-03-02 1995-02-23 스트렙토마이세스sp. P6621 FERM P2804의 발효액으로부터 클라불란산과 제약학적으로 허용가능한 이들의 염을 단리하는 신규한 방법 KR100293172B1 (ko)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
SIP-9400107 1994-03-02
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.
PCT/SI1995/000002 WO1995023870A1 (en) 1994-03-02 1995-02-23 Novel process for the isolation of clavulanic acid and of pharmaceutically acceptable salts thereof from the fermentation broth of streptomyces sp. p 6621 ferm p 2804

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KR970701786A true KR970701786A (ko) 1997-04-12
KR100293172B1 KR100293172B1 (ko) 2001-06-15

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KR1019960704806A KR100293172B1 (ko) 1994-03-02 1995-02-23 스트렙토마이세스sp. P6621 FERM P2804의 발효액으로부터 클라불란산과 제약학적으로 허용가능한 이들의 염을 단리하는 신규한 방법

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US (4) US5780274A (ko)
EP (1) EP0748387B1 (ko)
JP (1) JP2948661B2 (ko)
KR (1) KR100293172B1 (ko)
CN (1) CN1055694C (ko)
AT (1) ATE159549T1 (ko)
AU (1) AU694176B2 (ko)
BG (1) BG62213B1 (ko)
CA (1) CA2184619A1 (ko)
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DE (1) DE69500925T2 (ko)
DK (1) DK0748387T3 (ko)
ES (1) ES2108572T3 (ko)
FI (1) FI963408A (ko)
GR (1) GR3025942T3 (ko)
HU (1) HUT74944A (ko)
NO (1) NO318374B1 (ko)
NZ (1) NZ279958A (ko)
PL (1) PL180520B1 (ko)
RO (1) RO118760B1 (ko)
RU (1) RU2206613C2 (ko)
SI (1) SI9400107A (ko)
SK (1) SK279780B6 (ko)
WO (1) WO1995023870A1 (ko)
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CZ255796A3 (en) 1996-12-11
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