CA1234799A - Derives de cephalosporine - Google Patents

Derives de cephalosporine

Info

Publication number: CA1234799A
Authority: CA; Canada
Prior art keywords: cephalexin; hydrochloride; mindwrite; crystalline; alkanol
Prior art date: 1984-11-27
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

Application number

CA000531803A

Other languages

English (en)

Inventor

Joseph M. Indelicato

Gary L. Engel

Harry A. Rose

Kuo S. Yang

Lawrence J. Mcshane

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.)

Eli Lilly and Co

Original Assignee

Eli Lilly and Co

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.)

1984-11-27

Filing date

1987-03-11

Publication date

1988-04-05

1987-03-11 Application filed by Eli Lilly and Co filed Critical Eli Lilly and Co

1987-03-11 Priority to CA000531803A priority Critical patent/CA1234799A/fr

1988-04-05 Application granted granted Critical

1988-04-05 Publication of CA1234799A publication Critical patent/CA1234799A/fr

Status Expired legal-status Critical Current

Links

229930186147 Cephalosporin Natural products 0.000 title description 4
229940124587 cephalosporin Drugs 0.000 title description 4
150000001780 cephalosporins Chemical class 0.000 title description 4
LSBUIZREQYVRSY-CYJZLJNKSA-N (6r,7r)-7-[[(2r)-2-amino-2-phenylacetyl]amino]-3-methyl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid;hydrochloride Chemical compound Cl.C1([C@@H](N)C(=O)N[C@H]2[C@@H]3N(C2=O)C(=C(CS3)C)C(O)=O)=CC=CC=C1 LSBUIZREQYVRSY-CYJZLJNKSA-N 0.000 claims abstract description 51
229940084959 cephalexin hydrochloride Drugs 0.000 claims abstract description 51
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims abstract description 31
229910000041 hydrogen chloride Inorganic materials 0.000 claims abstract description 13
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 claims abstract description 13
239000000725 suspension Substances 0.000 claims abstract description 10
239000012453 solvate Substances 0.000 claims abstract 10
LFQSCWFLJHTTHZ-UHFFFAOYSA-N EtOH Substances CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 32
OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Natural products OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 29
238000000034 method Methods 0.000 claims description 10
230000008569 process Effects 0.000 claims description 9
239000002253 acid Substances 0.000 claims description 6
238000004519 manufacturing process Methods 0.000 claims description 5
229940047526 cephalexin monohydrate Drugs 0.000 claims 5
YGZIWEZFFBPCLN-UHFFFAOYSA-N n,3-bis(2-chloroethyl)-4-hydroperoxy-2-oxo-1,3,2$l^{5}-oxazaphosphinan-2-amine Chemical compound OOC1CCOP(=O)(NCCCl)N1CCCl YGZIWEZFFBPCLN-UHFFFAOYSA-N 0.000 claims 5
239000000126 substance Substances 0.000 claims 5
230000036571 hydration Effects 0.000 abstract description 4
238000006703 hydration reaction Methods 0.000 abstract description 4
230000003115 biocidal effect Effects 0.000 abstract 1
AVGYWQBCYZHHPN-CYJZLJNKSA-N cephalexin monohydrate Chemical compound O.C1([C@@H](N)C(=O)N[C@H]2[C@@H]3N(C2=O)C(=C(CS3)C)C(O)=O)=CC=CC=C1 AVGYWQBCYZHHPN-CYJZLJNKSA-N 0.000 abstract 1
229940106164 cephalexin Drugs 0.000 description 20
ZAIPMKNFIOOWCQ-UEKVPHQBSA-N cephalexin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@@H]3N(C2=O)C(=C(CS3)C)C(O)=O)=CC=CC=C1 ZAIPMKNFIOOWCQ-UEKVPHQBSA-N 0.000 description 20
150000001875 compounds Chemical class 0.000 description 13
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 12
239000000243 solution Substances 0.000 description 12
230000003204 osmotic effect Effects 0.000 description 11
BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 10
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 10
239000000463 material Substances 0.000 description 8
239000000047 product Substances 0.000 description 8
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 7
239000004615 ingredient Substances 0.000 description 7
239000000203 mixture Substances 0.000 description 7
238000009472 formulation Methods 0.000 description 6
229920000036 polyvinylpyrrolidone Polymers 0.000 description 6
235000013855 polyvinylpyrrolidone Nutrition 0.000 description 6
239000002002 slurry Substances 0.000 description 6
WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 5
239000012298 atmosphere Substances 0.000 description 5
229940069328 povidone Drugs 0.000 description 5
239000011541 reaction mixture Substances 0.000 description 5
RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 4
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 4
238000002441 X-ray diffraction Methods 0.000 description 4
239000004480 active ingredient Substances 0.000 description 4
230000015572 biosynthetic process Effects 0.000 description 4
229910052802 copper Inorganic materials 0.000 description 4
239000010949 copper Substances 0.000 description 4
239000002552 dosage form Substances 0.000 description 4
230000000694 effects Effects 0.000 description 4
239000012729 immediate-release (IR) formulation Substances 0.000 description 4
229960004592 isopropanol Drugs 0.000 description 4
239000011777 magnesium Substances 0.000 description 4
229910052749 magnesium Inorganic materials 0.000 description 4
238000000634 powder X-ray diffraction Methods 0.000 description 4
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
239000002775 capsule Substances 0.000 description 3
238000006243 chemical reaction Methods 0.000 description 3
238000013270 controlled release Methods 0.000 description 3
239000013078 crystal Substances 0.000 description 3
238000002425 crystallisation Methods 0.000 description 3
230000008025 crystallization Effects 0.000 description 3
238000005516 engineering process Methods 0.000 description 3
238000004128 high performance liquid chromatography Methods 0.000 description 3
239000008194 pharmaceutical composition Substances 0.000 description 3
239000000546 pharmaceutical excipient Substances 0.000 description 3
239000003053 toxin Substances 0.000 description 3
230000004580 weight loss Effects 0.000 description 3
208000035143 Bacterial infection Diseases 0.000 description 2
238000005169 Debye-Scherrer Methods 0.000 description 2
241000282320 Panthera leo Species 0.000 description 2
229920002472 Starch Polymers 0.000 description 2
239000013543 active substance Substances 0.000 description 2
208000022362 bacterial infectious disease Diseases 0.000 description 2
230000036765 blood level Effects 0.000 description 2
230000008859 change Effects 0.000 description 2
230000008034 disappearance Effects 0.000 description 2
239000012153 distilled water Substances 0.000 description 2
238000000921 elemental analysis Methods 0.000 description 2
239000012065 filter cake Substances 0.000 description 2
238000001914 filtration Methods 0.000 description 2
239000012530 fluid Substances 0.000 description 2
239000000543 intermediate Substances 0.000 description 2
JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
238000010899 nucleation Methods 0.000 description 2
150000003839 salts Chemical class 0.000 description 2
239000008107 starch Substances 0.000 description 2
235000019698 starch Nutrition 0.000 description 2
230000009466 transformation Effects 0.000 description 2
QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 1
239000004215 Carbon black (E152) Substances 0.000 description 1
235000010469 Glycine max Nutrition 0.000 description 1
244000068988 Glycine max Species 0.000 description 1
238000003109 Karl Fischer titration Methods 0.000 description 1
241001465754 Metazoa Species 0.000 description 1
229930006000 Sucrose Natural products 0.000 description 1
CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
235000018936 Vitellaria paradoxa Nutrition 0.000 description 1
DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
230000009471 action Effects 0.000 description 1
239000003242 anti bacterial agent Substances 0.000 description 1
230000000844 anti-bacterial effect Effects 0.000 description 1
239000012296 anti-solvent Substances 0.000 description 1
239000007864 aqueous solution Substances 0.000 description 1
210000001124 body fluid Anatomy 0.000 description 1
239000010839 body fluid Substances 0.000 description 1
230000037396 body weight Effects 0.000 description 1
239000007963 capsule composition Substances 0.000 description 1
229920003123 carboxymethyl cellulose sodium Polymers 0.000 description 1
229940063834 carboxymethylcellulose sodium Drugs 0.000 description 1
239000003795 chemical substances by application Substances 0.000 description 1
239000000599 controlled substance Substances 0.000 description 1
239000012050 conventional carrier Substances 0.000 description 1
238000000354 decomposition reaction Methods 0.000 description 1
238000004455 differential thermal analysis Methods 0.000 description 1
238000006073 displacement reaction Methods 0.000 description 1
238000004090 dissolution Methods 0.000 description 1
229940079593 drug Drugs 0.000 description 1
239000003814 drug Substances 0.000 description 1
239000003937 drug carrier Substances 0.000 description 1
238000012377 drug delivery Methods 0.000 description 1
238000001035 drying Methods 0.000 description 1
238000005538 encapsulation Methods 0.000 description 1
LJQKCYFTNDAAPC-UHFFFAOYSA-N ethanol;ethyl acetate Chemical compound CCO.CCOC(C)=O LJQKCYFTNDAAPC-UHFFFAOYSA-N 0.000 description 1
GCFHZZWXZLABBL-UHFFFAOYSA-N ethanol;hexane Chemical compound CCO.CCCCCC GCFHZZWXZLABBL-UHFFFAOYSA-N 0.000 description 1
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
239000012467 final product Substances 0.000 description 1
239000007789 gas Substances 0.000 description 1
239000007903 gelatin capsule Substances 0.000 description 1
239000011521 glass Substances 0.000 description 1
150000002334 glycols Chemical class 0.000 description 1
239000008187 granular material Substances 0.000 description 1
230000000887 hydrating effect Effects 0.000 description 1
229930195733 hydrocarbon Natural products 0.000 description 1
150000002430 hydrocarbons Chemical class 0.000 description 1
150000003840 hydrochlorides Chemical class 0.000 description 1
150000001261 hydroxy acids Chemical class 0.000 description 1
239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 1
238000010348 incorporation Methods 0.000 description 1
239000004310 lactic acid Substances 0.000 description 1
235000014655 lactic acid Nutrition 0.000 description 1
238000005259 measurement Methods 0.000 description 1
150000002734 metacrylic acid derivatives Chemical class 0.000 description 1
NBTOZLQBSIZIKS-UHFFFAOYSA-N methoxide Chemical compound [O-]C NBTOZLQBSIZIKS-UHFFFAOYSA-N 0.000 description 1
239000012452 mother liquor Substances 0.000 description 1
239000002245 particle Substances 0.000 description 1
230000000144 pharmacologic effect Effects 0.000 description 1
229920000642 polymer Polymers 0.000 description 1
239000001267 polyvinylpyrrolidone Substances 0.000 description 1
238000002360 preparation method Methods 0.000 description 1
230000002265 prevention Effects 0.000 description 1
230000002035 prolonged effect Effects 0.000 description 1
OGHBATFHNDZKSO-UHFFFAOYSA-N propan-2-olate Chemical compound CC(C)[O-] OGHBATFHNDZKSO-UHFFFAOYSA-N 0.000 description 1
238000010791 quenching Methods 0.000 description 1
230000008707 rearrangement Effects 0.000 description 1
229920006395 saturated elastomer Polymers 0.000 description 1
238000004513 sizing Methods 0.000 description 1
159000000000 sodium salts Chemical class 0.000 description 1
239000007787 solid Substances 0.000 description 1
239000002904 solvent Substances 0.000 description 1
238000003860 storage Methods 0.000 description 1
239000005720 sucrose Substances 0.000 description 1
238000013268 sustained release Methods 0.000 description 1
239000012730 sustained-release form Substances 0.000 description 1
238000003786 synthesis reaction Methods 0.000 description 1
239000007916 tablet composition Substances 0.000 description 1
230000001225 therapeutic effect Effects 0.000 description 1
238000002560 therapeutic procedure Methods 0.000 description 1
238000002411 thermogravimetry Methods 0.000 description 1
238000004448 titration Methods 0.000 description 1
238000004457 water analysis Methods 0.000 description 1

Landscapes

Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Cephalosporin Compounds (AREA)

CA000531803A 1984-11-27 1987-03-11 Derives de cephalosporine Expired CA1234799A (fr)

Priority Applications (1)

Application Number	Priority Date	Filing Date	Title
CA000531803A CA1234799A (fr)	1984-11-27	1987-03-11	Derives de cephalosporine

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
CA000468655A CA1231941A (fr)	1984-11-27	1984-11-27	Derives de cephalosporine
CA000531803A CA1234799A (fr)	1984-11-27	1987-03-11	Derives de cephalosporine

Related Parent Applications (1)

Application Number	Title	Priority Date	Filing Date
CA000468655A Division CA1231941A (fr)	1984-11-27	1984-11-27	Derives de cephalosporine

Publications (1)

Publication Number	Publication Date
CA1234799A true CA1234799A (fr)	1988-04-05

Family

ID=4129230

Family Applications (2)

Application Number	Title	Priority Date	Filing Date
CA000468655A Expired CA1231941A (fr)	1984-11-27	1984-11-27	Derives de cephalosporine
CA000531803A Expired CA1234799A (fr)	1984-11-27	1987-03-11	Derives de cephalosporine

Family Applications Before (1)

Application Number	Title	Priority Date	Filing Date
CA000468655A Expired CA1231941A (fr)	1984-11-27	1984-11-27	Derives de cephalosporine

Country Status (1)

Country	Link
CA (2)	CA1231941A (fr)

1984
- 1984-11-27 CA CA000468655A patent/CA1231941A/fr not_active Expired
1987
- 1987-03-11 CA CA000531803A patent/CA1234799A/fr not_active Expired

Also Published As

Publication number	Publication date
CA1231941A (fr)	1988-01-26

Legal Events

Date	Code	Title	Description
2005-04-05	MKEX	Expiry

Publication	Publication Date	Title
KR100245938B1 (ko)	2000-04-01	트리아졸릴티오메틸티오 세팔로스포린 염산염, 그의 결정성 수화물 및 이들의 제조방법
AU703634B2 (en)	1999-03-25	Novel crystalline forms of anhydrous 7-{(1alpha,5alpha, 6alpha)-6-amino-3-azabicyclo(3.1.0)hex-3-y1}-6-fluoro-1- (2,4-difluorophenyl)-1,4-dihydro-4-oxo-1,8-naphthyridine-3- carboxylic acid, methanesulfonic acid salt.
EP0143658B1 (fr)	1989-03-22	Dérivés de céphalosporines
KR20050002872A (ko)	2005-01-10	9-데옥소-9ａ-아자-9ａ-메틸-9ａ-호모에리트로마이신 ａ의동종 구조의 유사 다형질체
CA1202317A (fr)	1986-03-25	Thioesters de l'acide acetylsalicylique, procede de preparation et composes pharmaceutiques les contenant
US20040063948A1 (en)	2004-04-01	Crystalline fluoroquinolone arginine salt form
CA1234799A (fr)	1988-04-05	Derives de cephalosporine
WO2002009640A2 (fr)	2002-02-07	Élaboration d'azithromycine anhydre
JP2013184902A (ja)	2013-09-19	リファキシミン含有結晶
US4882325A (en)	1989-11-21	Crystalline 1,1-dioxopenicillanoyloxymethyl 6-(d-amino-phenylacetamido)penicillanate napsylate and method of using the same
JP2723088B2 (ja)	1998-03-09	セファロスポリン化合物の新規な結晶
JP2575590B2 (ja)	1997-01-29	トリアゾリルチオメチルチオセファロスポリン塩酸塩およびその水和物結晶ならびにそれらの製法
US4316018A (en)	1982-02-16	Crystallized cephalosporin salts
MXPA01012325A (es)	2002-07-22	Formas polimorfas de un citrato cristalino de azobiciclo(2.2.2)octan-3-amina y sus composiciones farmaceuticas.
US4474780A (en)	1984-10-02	Crystalline cephalosporin
IE52519B1 (en)	1987-11-25	4-(1-imidazolylmethyl)cinnamic acid hydrochloride monohydrate,method of preparation thereof,and pharmaceutical composition containing same
JP3012986B2 (ja)	2000-02-28	セフェム化合物及びその製造法
JP3242975B2 (ja)	2001-12-25	消化管運動機能改善剤
CA1202617A (fr)	1986-04-01	Napsylate de bacampicilline
GB2084572A (en)	1982-04-15	1,1-Dioxopenicillanoyloxymethyl 6-(D- alpha -amino- alpha -phenylacetamido)penicillanate napsylate
JP2649101B2 (ja)	1997-09-03	イソセフェム誘導体およびその製造方法
EP1918289A2 (fr)	2008-05-07	Forme cristalline de sel d'arginine de fluoroquinolone
MXPA01008780A (en)	2002-05-09	Processes for making pharmaceutical oral ecb formulations and compositions