CA2710642C - Cristallisation d'iodixanol par ultra-sons - Google Patents

Cristallisation d'iodixanol par ultra-sons Download PDF

Info

Publication number: CA2710642C
Authority: CA; Canada
Prior art keywords: iodixanol; crystallization; ultrasound; purification; bis
Prior art date: 2009-07-21
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 - Fee Related

Application number

CA 2710642

Other languages

English (en)

Other versions

CA2710642A1 (fr

Inventor

Khalid Hussain

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.)

GE Healthcare AS

Original Assignee

GE Healthcare AS

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.)

2009-07-21

Filing date

2010-07-20

Publication date

2012-10-30

2009-11-04 Priority claimed from US12/611,977 external-priority patent/US7999135B2/en

2010-07-20 Application filed by GE Healthcare AS filed Critical GE Healthcare AS

2011-01-21 Publication of CA2710642A1 publication Critical patent/CA2710642A1/fr

2012-10-30 Application granted granted Critical

2012-10-30 Publication of CA2710642C publication Critical patent/CA2710642C/fr

Status Expired - Fee Related legal-status Critical Current

2030-07-20 Anticipated expiration legal-status Critical

Links

229960004359 iodixanol Drugs 0.000 title claims abstract description 41
NBQNWMBBSKPBAY-UHFFFAOYSA-N iodixanol Chemical compound IC=1C(C(=O)NCC(O)CO)=C(I)C(C(=O)NCC(O)CO)=C(I)C=1N(C(=O)C)CC(O)CN(C(C)=O)C1=C(I)C(C(=O)NCC(O)CO)=C(I)C(C(=O)NCC(O)CO)=C1I NBQNWMBBSKPBAY-UHFFFAOYSA-N 0.000 title claims abstract description 41
238000002425 crystallisation Methods 0.000 title claims abstract description 35
230000008025 crystallization Effects 0.000 title claims abstract description 33
238000002604 ultrasonography Methods 0.000 title claims abstract description 19
238000000746 purification Methods 0.000 claims abstract description 15
238000000034 method Methods 0.000 claims description 45
229940126062 Compound A Drugs 0.000 claims description 11
NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 claims description 11
239000013078 crystal Substances 0.000 claims description 9
239000011541 reaction mixture Substances 0.000 claims description 7
238000005054 agglomeration Methods 0.000 claims description 5
230000002776 aggregation Effects 0.000 claims description 5
239000012535 impurity Substances 0.000 claims description 5
229960001025 iohexol Drugs 0.000 claims description 5
NTHXOOBQLCIOLC-UHFFFAOYSA-N iohexol Chemical compound OCC(O)CN(C(=O)C)C1=C(I)C(C(=O)NCC(O)CO)=C(I)C(C(=O)NCC(O)CO)=C1I NTHXOOBQLCIOLC-UHFFFAOYSA-N 0.000 claims description 5
230000014759 maintenance of location Effects 0.000 claims description 4
238000004007 reversed phase HPLC Methods 0.000 claims description 3
238000006471 dimerization reaction Methods 0.000 claims description 2
238000004519 manufacturing process Methods 0.000 abstract description 12
239000012043 crude product Substances 0.000 description 9
239000002245 particle Substances 0.000 description 8
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 7
239000000243 solution Substances 0.000 description 7
ARXJGSRGQADJSQ-UHFFFAOYSA-N 1-methoxypropan-2-ol Chemical compound COCC(C)O ARXJGSRGQADJSQ-UHFFFAOYSA-N 0.000 description 6
239000000523 sample Substances 0.000 description 6
238000006243 chemical reaction Methods 0.000 description 5
239000011549 crystallization solution Substances 0.000 description 5
238000005406 washing Methods 0.000 description 5
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
239000008186 active pharmaceutical agent Substances 0.000 description 4
239000003795 chemical substances by application Substances 0.000 description 4
229940088679 drug related substance Drugs 0.000 description 4
239000012467 final product Substances 0.000 description 4
239000000203 mixture Substances 0.000 description 4
239000000126 substance Substances 0.000 description 4
BRLQWZUYTZBJKN-UHFFFAOYSA-N Epichlorohydrin Chemical compound ClCC1CO1 BRLQWZUYTZBJKN-UHFFFAOYSA-N 0.000 description 3
238000002360 preparation method Methods 0.000 description 3
239000000047 product Substances 0.000 description 3
239000002904 solvent Substances 0.000 description 3
238000003786 synthesis reaction Methods 0.000 description 3
XNWFRZJHXBZDAG-UHFFFAOYSA-N 2-METHOXYETHANOL Chemical compound COCCO XNWFRZJHXBZDAG-UHFFFAOYSA-N 0.000 description 2
BHCBLTRDEYPMFZ-UHFFFAOYSA-N 5-acetamido-1-n,3-n-bis(2,3-dihydroxypropyl)-2,4,6-triiodobenzene-1,3-dicarboxamide Chemical compound CC(=O)NC1=C(I)C(C(=O)NCC(O)CO)=C(I)C(C(=O)NCC(O)CO)=C1I BHCBLTRDEYPMFZ-UHFFFAOYSA-N 0.000 description 2
NBDAHKQJXVLAID-UHFFFAOYSA-N 5-nitroisophthalic acid Chemical compound OC(=O)C1=CC(C(O)=O)=CC([N+]([O-])=O)=C1 NBDAHKQJXVLAID-UHFFFAOYSA-N 0.000 description 2
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
239000007795 chemical reaction product Substances 0.000 description 2
238000005660 chlorination reaction Methods 0.000 description 2
239000002872 contrast media Substances 0.000 description 2
229940126534 drug product Drugs 0.000 description 2
238000001914 filtration Methods 0.000 description 2
238000010438 heat treatment Methods 0.000 description 2
239000012452 mother liquor Substances 0.000 description 2
238000010899 nucleation Methods 0.000 description 2
239000000825 pharmaceutical preparation Substances 0.000 description 2
238000004262 preparative liquid chromatography Methods 0.000 description 2
238000010992 reflux Methods 0.000 description 2
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
238000010626 work up procedure Methods 0.000 description 2
KIHQZLPHVZKELA-UHFFFAOYSA-N 1,3-dibromopropan-2-ol Chemical compound BrCC(O)CBr KIHQZLPHVZKELA-UHFFFAOYSA-N 0.000 description 1
DEWLEGDTCGBNGU-UHFFFAOYSA-N 1,3-dichloropropan-2-ol Chemical compound ClCC(O)CCl DEWLEGDTCGBNGU-UHFFFAOYSA-N 0.000 description 1
KFZMGEQAYNKOFK-UHFFFAOYSA-N 2-propanol Substances CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 1
JEZJSNULLBSYHV-UHFFFAOYSA-N 5-amino-2,4,6-triiodobenzene-1,3-dicarboxylic acid Chemical compound NC1=C(I)C(C(O)=O)=C(I)C(C(O)=O)=C1I JEZJSNULLBSYHV-UHFFFAOYSA-N 0.000 description 1
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 description 1
239000002253 acid Substances 0.000 description 1
150000008064 anhydrides Chemical class 0.000 description 1
239000007864 aqueous solution Substances 0.000 description 1
230000015572 biosynthetic process Effects 0.000 description 1
238000009835 boiling Methods 0.000 description 1
238000001311 chemical methods and process Methods 0.000 description 1
239000003153 chemical reaction reagent Substances 0.000 description 1
230000000052 comparative effect Effects 0.000 description 1
239000000539 dimer Substances 0.000 description 1
230000007613 environmental effect Effects 0.000 description 1
238000009472 formulation Methods 0.000 description 1
229910052740 iodine Inorganic materials 0.000 description 1
239000011630 iodine Substances 0.000 description 1
238000004811 liquid chromatography Methods 0.000 description 1
VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 1
239000003960 organic solvent Substances 0.000 description 1
XTUSEBKMEQERQV-UHFFFAOYSA-N propan-2-ol;hydrate Chemical compound O.CC(C)O XTUSEBKMEQERQV-UHFFFAOYSA-N 0.000 description 1
ULWHHBHJGPPBCO-UHFFFAOYSA-N propane-1,1-diol Chemical compound CCC(O)O ULWHHBHJGPPBCO-UHFFFAOYSA-N 0.000 description 1
239000007858 starting material Substances 0.000 description 1
239000013638 trimer Substances 0.000 description 1

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Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

CA 2710642 2009-07-21 2010-07-20 Cristallisation d'iodixanol par ultra-sons Expired - Fee Related CA2710642C (fr)

Applications Claiming Priority (4)

Application Number	Priority Date	Filing Date	Title
US22710809P	2009-07-21	2009-07-21
US61/227,108		2009-07-21
US12/611,977		2009-11-04
US12/611,977 US7999135B2 (en)	2009-07-21	2009-11-04	Crystallization of iodixanol using ultrasound

Publications (2)

Publication Number	Publication Date
CA2710642A1 CA2710642A1 (fr)	2011-01-21
CA2710642C true CA2710642C (fr)	2012-10-30

Family

ID=43495959

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA 2710642 Expired - Fee Related CA2710642C (fr)	2009-07-21	2010-07-20	Cristallisation d'iodixanol par ultra-sons

Country Status (1)

Country	Link
CA (1)	CA2710642C (fr)

2010
- 2010-07-20 CA CA 2710642 patent/CA2710642C/fr not_active Expired - Fee Related

Also Published As

Publication number	Publication date
CA2710642A1 (fr)	2011-01-21

Legal Events

Date	Code	Title	Description
2011-05-13	EEER	Examination request
2017-08-31	MKLA	Lapsed	Effective date: 20170720

Publication	Publication Date	Title
CA2575088C (fr)	2012-10-30	Elaboration d'iodixanol
US8389765B2 (en)	2013-03-05	Purification of iodixanol
KR100996769B1 (ko)	2010-11-25	비-이온성 ｘ-선 조영제에 대한 중간체의 결정화에서의 용매 감소 방법
US20110021822A1 (en)	2011-01-27	continuous deacetylation and purification process in synthesis of non-ionic x-ray contrast agents
EP1966110B1 (fr)	2013-04-24	Procede de purification de l'iodixanol
EP2277856B1 (fr)	2012-02-22	Cristallisation d'iodixanol utilisant des ultrasons
EP2277855B1 (fr)	2011-11-09	Cristallisation d'iodixanol utilisant le broyage
CA2710642C (fr)	2012-10-30	Cristallisation d'iodixanol par ultra-sons
CA2710577C (fr)	2012-09-18	Cristallisation d'iodixanol par broyage
CA2707173C (fr)	2011-08-02	Cristallisation d'iodixanol dans de l'isopropanol et du methanol