CA1105404A - .alpha.-AMYLASE INHIBITOR FROM A STREPTOMYCETE AND PROCESS FOR ITS PREPARATION - Google Patents
.alpha.-AMYLASE INHIBITOR FROM A STREPTOMYCETE AND PROCESS FOR ITS PREPARATIONInfo
- Publication number
- CA1105404A CA1105404A CA295,189A CA295189A CA1105404A CA 1105404 A CA1105404 A CA 1105404A CA 295189 A CA295189 A CA 295189A CA 1105404 A CA1105404 A CA 1105404A
- Authority
- CA
- Canada
- Prior art keywords
- inhibitor
- culture
- amylase
- culture medium
- glycoside hydrolase
- 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
Links
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- 230000002730 additional effect Effects 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 102000016679 alpha-Glucosidases Human genes 0.000 description 1
- 108010028144 alpha-Glucosidases Proteins 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 229940025131 amylases Drugs 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 150000001450 anions Chemical class 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 230000008033 biological extinction Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 229940041514 candida albicans extract Drugs 0.000 description 1
- 239000005018 casein Substances 0.000 description 1
- BECPQYXYKAMYBN-UHFFFAOYSA-N casein, tech. Chemical compound NCCCCC(C(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(CC(C)C)N=C(O)C(CCC(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(C(C)O)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(COP(O)(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(N)CC1=CC=CC=C1 BECPQYXYKAMYBN-UHFFFAOYSA-N 0.000 description 1
- 235000021240 caseins Nutrition 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 229960002376 chymotrypsin Drugs 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 235000008504 concentrate Nutrition 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 239000002178 crystalline material Substances 0.000 description 1
- 239000012531 culture fluid Substances 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 235000013681 dietary sucrose Nutrition 0.000 description 1
- AIUDWMLXCFRVDR-UHFFFAOYSA-N dimethyl 2-(3-ethyl-3-methylpentyl)propanedioate Chemical compound CCC(C)(CC)CCC(C(=O)OC)C(=O)OC AIUDWMLXCFRVDR-UHFFFAOYSA-N 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 238000001962 electrophoresis Methods 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 238000006911 enzymatic reaction Methods 0.000 description 1
- 229940088598 enzyme Drugs 0.000 description 1
- 239000003925 fat Substances 0.000 description 1
- 239000012065 filter cake Substances 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 230000037406 food intake Effects 0.000 description 1
- 238000005227 gel permeation chromatography Methods 0.000 description 1
- 229960005150 glycerol Drugs 0.000 description 1
- 229910052588 hydroxylapatite Inorganic materials 0.000 description 1
- 230000035879 hyperinsulinaemia Effects 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- CDAISMWEOUEBRE-GPIVLXJGSA-N inositol Chemical compound O[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@H](O)[C@@H]1O CDAISMWEOUEBRE-GPIVLXJGSA-N 0.000 description 1
- 229960000367 inositol Drugs 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 230000003914 insulin secretion Effects 0.000 description 1
- 238000005342 ion exchange Methods 0.000 description 1
- 238000004255 ion exchange chromatography Methods 0.000 description 1
- 230000002427 irreversible effect Effects 0.000 description 1
- 229960001375 lactose Drugs 0.000 description 1
- 230000004132 lipogenesis Effects 0.000 description 1
- 238000002803 maceration Methods 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 235000012054 meals Nutrition 0.000 description 1
- JDSHMPZPIAZGSV-UHFFFAOYSA-N melamine Chemical compound NC1=NC(N)=NC(N)=N1 JDSHMPZPIAZGSV-UHFFFAOYSA-N 0.000 description 1
- 235000013336 milk Nutrition 0.000 description 1
- 239000008267 milk Substances 0.000 description 1
- 210000004080 milk Anatomy 0.000 description 1
- 235000013379 molasses Nutrition 0.000 description 1
- 239000002808 molecular sieve Substances 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 210000001331 nose Anatomy 0.000 description 1
- 102000039446 nucleic acids Human genes 0.000 description 1
- 108020004707 nucleic acids Proteins 0.000 description 1
- 150000007523 nucleic acids Chemical class 0.000 description 1
- 150000002482 oligosaccharides Polymers 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- XYJRXVWERLGGKC-UHFFFAOYSA-D pentacalcium;hydroxide;triphosphate Chemical compound [OH-].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O XYJRXVWERLGGKC-UHFFFAOYSA-D 0.000 description 1
- 229940111202 pepsin Drugs 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 239000008055 phosphate buffer solution Substances 0.000 description 1
- 235000011007 phosphoric acid Nutrition 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 230000001376 precipitating effect Effects 0.000 description 1
- 201000009104 prediabetes syndrome Diseases 0.000 description 1
- 230000017854 proteolysis Effects 0.000 description 1
- 230000002797 proteolythic effect Effects 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- CDAISMWEOUEBRE-UHFFFAOYSA-N scyllo-inosotol Natural products OC1C(O)C(O)C(O)C(O)C1O CDAISMWEOUEBRE-UHFFFAOYSA-N 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 238000001694 spray drying Methods 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 238000000967 suction filtration Methods 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 230000002110 toxicologic effect Effects 0.000 description 1
- 231100000027 toxicology Toxicity 0.000 description 1
- 229960001322 trypsin Drugs 0.000 description 1
- 239000012138 yeast extract Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/195—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria
- C07K14/36—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria from Actinomyces; from Streptomyces (G)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
-
- 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
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/99—Enzyme inactivation by chemical treatment
-
- 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
-
- 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
- Y10S530/00—Chemistry: natural resins or derivatives; peptides or proteins; lignins or reaction products thereof
- Y10S530/82—Proteins from microorganisms
-
- 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
- Y10S530/00—Chemistry: natural resins or derivatives; peptides or proteins; lignins or reaction products thereof
- Y10S530/82—Proteins from microorganisms
- Y10S530/823—Lower fungi, e.g. mold
-
- 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
- Y10S530/00—Chemistry: natural resins or derivatives; peptides or proteins; lignins or reaction products thereof
- Y10S530/82—Proteins from microorganisms
- Y10S530/825—Bacteria
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- General Chemical & Material Sciences (AREA)
- Biochemistry (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- Diabetes (AREA)
- Public Health (AREA)
- Biomedical Technology (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Veterinary Medicine (AREA)
- Gastroenterology & Hepatology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Biophysics (AREA)
- Obesity (AREA)
- Hematology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Animal Behavior & Ethology (AREA)
- Biotechnology (AREA)
- Microbiology (AREA)
- General Engineering & Computer Science (AREA)
- Emergency Medicine (AREA)
- Endocrinology (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Peptides Or Proteins (AREA)
- Compounds Of Unknown Constitution (AREA)
- Enzymes And Modification Thereof (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DEP2701890.2 | 1977-01-19 | ||
| DE2701890A DE2701890C2 (de) | 1977-01-19 | 1977-01-19 | Peptielischer Glycosidhydrolase-Inhibitor aus einem Streptomyceten und seine Verwendung |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1105404A true CA1105404A (en) | 1981-07-21 |
Family
ID=5998949
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA295,189A Expired CA1105404A (en) | 1977-01-19 | 1978-01-18 | .alpha.-AMYLASE INHIBITOR FROM A STREPTOMYCETE AND PROCESS FOR ITS PREPARATION |
Country Status (10)
| Country | Link |
|---|---|
| US (3) | US4226764A (en, 2012) |
| JP (1) | JPS5390201A (en, 2012) |
| AT (1) | AT363891B (en, 2012) |
| BE (1) | BE863089A (en, 2012) |
| CA (1) | CA1105404A (en, 2012) |
| DE (1) | DE2701890C2 (en, 2012) |
| ES (1) | ES465940A1 (en, 2012) |
| FR (1) | FR2378041A1 (en, 2012) |
| GB (1) | GB1599372A (en, 2012) |
| NL (1) | NL7800630A (en, 2012) |
Families Citing this family (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2900591A1 (de) * | 1979-01-09 | 1980-07-17 | Bayer Ag | Antibiotica, ein verfahren zu ihrer herstellung sowie ihre verwendung als pflanzenschutzmittel |
| DE2928137A1 (de) | 1979-07-12 | 1981-02-05 | Bayer Ag | Neue nikkomycine, ein verfahren zu ihrer herstellung sowie ihre verwendung als schaedlingsbekaempfungsmittel |
| JPS5910193B2 (ja) * | 1980-06-04 | 1984-03-07 | 富士レビオ株式会社 | アミラ−ゼ阻害物質ａｉ−ｂの製造法 |
| ES8207217A1 (es) * | 1980-10-09 | 1982-09-01 | Hoechst Ag | Procedimiento para la preparacion de un inactivador de alfa-amilasa |
| JPS5885899A (ja) * | 1981-11-16 | 1983-05-23 | Fujirebio Inc | アミラ−ゼインヒビタ−およびその製造法 |
| DK520784A (da) * | 1984-01-21 | 1985-07-22 | Hoechst Ag | Cycliske polypeptider, deres fremstilling og anvendelse |
| DE3536182A1 (de) * | 1985-10-10 | 1987-04-16 | Hoechst Ag | Promotor-anordnung fuer streptomyceten-vektoren |
| GB2199582A (en) * | 1987-01-07 | 1988-07-13 | Bayer Ag | Analogues of pancreatic secretory trypsin inhibitor |
| RU2355755C1 (ru) * | 2008-01-09 | 2009-05-20 | Государственное учреждение Всероссийский научно-исследовательский институт пищевых ароматизаторов, кислот и красителей Российской академии сельскохозяйственных наук (ГУ ВНИИПАКК) | ШТАММ АКТИНОМИЦЕТА Streptomyces lucensis - ПРОДУЦЕНТ ИНГИБИТОРА ГЛИКОЗИДАЗ |
| RU2495930C1 (ru) * | 2012-06-27 | 2013-10-20 | Государственное научное учреждение Всероссийский научно-исследовательский институт пищевых ароматизаторов, кислот и красителей Российской академии сельскохозяйственных наук (ГНУ ВНИИПАКК Россельхозакадемии) | Способ получения ингибитора гликозидаз |
Family Cites Families (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IE34869B1 (en) | 1970-01-29 | 1975-09-03 | Bayer Ag | Amylase inhibitor,processes for its production,and compositions containing it |
| DE2064092C2 (de) * | 1970-12-28 | 1983-06-01 | Bayer Ag, 5090 Leverkusen | Inhibitoren für Glykosidhydrolasen aus Actinomyceten |
| JPS5111197B1 (en, 2012) * | 1971-05-31 | 1976-04-09 | ||
| DE2209834C3 (de) * | 1972-03-01 | 1978-04-20 | Bayer Ag, 5090 Leverkusen | Herstellung von Saccharase-Inhibitoren |
| DE2209833C3 (de) * | 1972-03-01 | 1978-06-01 | Bayer Ag, 5090 Leverkusen | Herstellung eines Amylaseinhibitors |
| US4010258A (en) | 1974-03-15 | 1977-03-01 | Ajinomoto Co., Inc. | Microbial amylase inhibitor and preparation thereof with the use of streptomyces diasticus var. amylostaticus |
| JPS5259475A (en) * | 1975-11-07 | 1977-05-16 | Hitachi Ltd | Palletizer for mixed transportation |
| FR2338707A1 (fr) * | 1976-01-22 | 1977-08-19 | Rhone Poulenc Ind | Nouvel inhibiteur de glyco-hydrolases et sa preparation par culture d'un streptomyces |
| DE2716050A1 (de) * | 1977-04-09 | 1978-10-19 | Hoechst Ag | Alpha-amylase-inhibitor aus einem streptomyceten und verfahren zu seiner gewinnung |
-
1977
- 1977-01-19 DE DE2701890A patent/DE2701890C2/de not_active Expired
-
1978
- 1978-01-13 ES ES465940A patent/ES465940A1/es not_active Expired
- 1978-01-17 US US05/870,247 patent/US4226764A/en not_active Expired - Lifetime
- 1978-01-18 AT AT0035578A patent/AT363891B/de not_active IP Right Cessation
- 1978-01-18 NL NL7800630A patent/NL7800630A/xx not_active Application Discontinuation
- 1978-01-18 FR FR7801387A patent/FR2378041A1/fr active Granted
- 1978-01-18 CA CA295,189A patent/CA1105404A/en not_active Expired
- 1978-01-19 JP JP479678A patent/JPS5390201A/ja active Granted
- 1978-01-19 BE BE184460A patent/BE863089A/xx not_active IP Right Cessation
- 1978-01-19 GB GB2226/78A patent/GB1599372A/en not_active Expired
-
1980
- 1980-01-02 US US06/109,170 patent/US4282318A/en not_active Expired - Lifetime
-
1981
- 1981-02-23 US US06/237,097 patent/US4339436A/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| US4339436A (en) | 1982-07-13 |
| DE2701890A1 (de) | 1978-07-27 |
| JPS6236040B2 (en, 2012) | 1987-08-05 |
| AT363891B (de) | 1981-09-10 |
| JPS5390201A (en) | 1978-08-08 |
| FR2378041B1 (en, 2012) | 1980-07-04 |
| GB1599372A (en) | 1981-09-30 |
| ATA35578A (de) | 1981-02-15 |
| DE2701890C2 (de) | 1983-08-04 |
| FR2378041A1 (fr) | 1978-08-18 |
| NL7800630A (nl) | 1978-07-21 |
| US4226764A (en) | 1980-10-07 |
| BE863089A (fr) | 1978-07-19 |
| ES465940A1 (es) | 1978-09-16 |
| US4282318A (en) | 1981-08-04 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MKEX | Expiry |