WO1999024391B1 - Radio-opaque polymer biomaterials - Google Patents

Radio-opaque polymer biomaterials

Info

Publication number
WO1999024391B1
WO1999024391B1 PCT/US1998/023777 US9823777W WO9924391B1 WO 1999024391 B1 WO1999024391 B1 WO 1999024391B1 US 9823777 W US9823777 W US 9823777W WO 9924391 B1 WO9924391 B1 WO 9924391B1
Authority
WO
WIPO (PCT)
Prior art keywords
group
independently
chj
bromine
radio
Prior art date
Application number
PCT/US1998/023777
Other languages
French (fr)
Other versions
WO1999024391A1 (en
Inventor
Joachim B Kohn
Durgadas Bolikal
Sanyog M Pendharkar
Original Assignee
Univ Rutgers
Joachim B Kohn
Durgadas Bolikal
Sanyog M Pendharkar
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
Priority to CA002308721A priority Critical patent/CA2308721C/en
Application filed by Univ Rutgers, Joachim B Kohn, Durgadas Bolikal, Sanyog M Pendharkar filed Critical Univ Rutgers
Priority to AT98959390T priority patent/ATE307110T1/en
Priority to US09/554,027 priority patent/US6475477B1/en
Priority to EP98959390A priority patent/EP1036057B1/en
Priority to AU15199/99A priority patent/AU737151B2/en
Priority to JP2000520405A priority patent/JP4465105B2/en
Priority to DE69831973T priority patent/DE69831973T2/en
Publication of WO1999024391A1 publication Critical patent/WO1999024391A1/en
Publication of WO1999024391B1 publication Critical patent/WO1999024391B1/en
Priority to US10/691,750 priority patent/US7056493B2/en
Priority to US11/024,355 priority patent/US7250154B2/en
Priority to US11/418,943 priority patent/US20060204440A1/en
Priority to US11/933,780 priority patent/US20080107709A1/en

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    • C08ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08GMACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
    • C08G64/00Macromolecular compounds obtained by reactions forming a carbonic ester link in the main chain of the macromolecule
    • C08G64/04Aromatic polycarbonates
    • C08G64/06Aromatic polycarbonates not containing aliphatic unsaturation
    • C08G64/08Aromatic polycarbonates not containing aliphatic unsaturation containing atoms other than carbon, hydrogen or oxygen
    • C08G64/12Aromatic polycarbonates not containing aliphatic unsaturation containing atoms other than carbon, hydrogen or oxygen containing nitrogen
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K49/00Preparations for testing in vivo
    • A61K49/04X-ray contrast preparations
    • A61K49/0433X-ray contrast preparations containing an organic halogenated X-ray contrast-enhancing agent
    • A61K49/0438Organic X-ray contrast-enhancing agent comprising an iodinated group or an iodine atom, e.g. iopamidol
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K49/00Preparations for testing in vivo
    • A61K49/04X-ray contrast preparations
    • A61K49/0433X-ray contrast preparations containing an organic halogenated X-ray contrast-enhancing agent
    • A61K49/0442Polymeric X-ray contrast-enhancing agent comprising a halogenated group
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K49/00Preparations for testing in vivo
    • A61K49/04X-ray contrast preparations
    • A61K49/0433X-ray contrast preparations containing an organic halogenated X-ray contrast-enhancing agent
    • A61K49/0447Physical forms of mixtures of two different X-ray contrast-enhancing agents, containing at least one X-ray contrast-enhancing agent which is a halogenated organic compound
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L31/00Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/08Materials for coatings
    • A61L31/10Macromolecular materials
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L31/00Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/14Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L31/16Biologically active materials, e.g. therapeutic substances
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L31/00Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/14Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L31/18Materials at least partially X-ray or laser opaque
    • CCHEMISTRY; METALLURGY
    • C08ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08GMACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
    • C08G63/00Macromolecular compounds obtained by reactions forming a carboxylic ester link in the main chain of the macromolecule
    • C08G63/66Polyesters containing oxygen in the form of ether groups
    • C08G63/668Polyesters containing oxygen in the form of ether groups derived from polycarboxylic acids and polyhydroxy compounds
    • C08G63/672Dicarboxylic acids and dihydroxy compounds
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    • C08ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08GMACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
    • C08G63/00Macromolecular compounds obtained by reactions forming a carboxylic ester link in the main chain of the macromolecule
    • C08G63/68Polyesters containing atoms other than carbon, hydrogen and oxygen
    • C08G63/682Polyesters containing atoms other than carbon, hydrogen and oxygen containing halogens
    • C08G63/6824Polyesters containing atoms other than carbon, hydrogen and oxygen containing halogens derived from polycarboxylic acids and polyhydroxy compounds
    • C08G63/6826Dicarboxylic acids and dihydroxy compounds
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    • C08ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08GMACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
    • C08G63/00Macromolecular compounds obtained by reactions forming a carboxylic ester link in the main chain of the macromolecule
    • C08G63/68Polyesters containing atoms other than carbon, hydrogen and oxygen
    • C08G63/685Polyesters containing atoms other than carbon, hydrogen and oxygen containing nitrogen
    • C08G63/6854Polyesters containing atoms other than carbon, hydrogen and oxygen containing nitrogen derived from polycarboxylic acids and polyhydroxy compounds
    • C08G63/6856Dicarboxylic acids and dihydroxy compounds
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    • C08ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08GMACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
    • C08G64/00Macromolecular compounds obtained by reactions forming a carbonic ester link in the main chain of the macromolecule
    • C08G64/04Aromatic polycarbonates
    • C08G64/06Aromatic polycarbonates not containing aliphatic unsaturation
    • C08G64/08Aromatic polycarbonates not containing aliphatic unsaturation containing atoms other than carbon, hydrogen or oxygen
    • C08G64/10Aromatic polycarbonates not containing aliphatic unsaturation containing atoms other than carbon, hydrogen or oxygen containing halogens
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    • C08ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08GMACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
    • C08G64/00Macromolecular compounds obtained by reactions forming a carbonic ester link in the main chain of the macromolecule
    • C08G64/16Aliphatic-aromatic or araliphatic polycarbonates
    • C08G64/1608Aliphatic-aromatic or araliphatic polycarbonates saturated
    • C08G64/1625Aliphatic-aromatic or araliphatic polycarbonates saturated containing atoms other than carbon, hydrogen or oxygen
    • C08G64/1633Aliphatic-aromatic or araliphatic polycarbonates saturated containing atoms other than carbon, hydrogen or oxygen containing halogens
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    • C08ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08GMACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
    • C08G64/00Macromolecular compounds obtained by reactions forming a carbonic ester link in the main chain of the macromolecule
    • C08G64/16Aliphatic-aromatic or araliphatic polycarbonates
    • C08G64/1608Aliphatic-aromatic or araliphatic polycarbonates saturated
    • C08G64/1625Aliphatic-aromatic or araliphatic polycarbonates saturated containing atoms other than carbon, hydrogen or oxygen
    • C08G64/1641Aliphatic-aromatic or araliphatic polycarbonates saturated containing atoms other than carbon, hydrogen or oxygen containing nitrogen
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    • C08ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08GMACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
    • C08G64/00Macromolecular compounds obtained by reactions forming a carbonic ester link in the main chain of the macromolecule
    • C08G64/18Block or graft polymers
    • C08G64/183Block or graft polymers containing polyether sequences
    • CCHEMISTRY; METALLURGY
    • C08ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08GMACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
    • C08G65/00Macromolecular compounds obtained by reactions forming an ether link in the main chain of the macromolecule
    • C08G65/02Macromolecular compounds obtained by reactions forming an ether link in the main chain of the macromolecule from cyclic ethers by opening of the heterocyclic ring
    • C08G65/32Polymers modified by chemical after-treatment
    • C08G65/329Polymers modified by chemical after-treatment with organic compounds
    • C08G65/331Polymers modified by chemical after-treatment with organic compounds containing oxygen
    • C08G65/3311Polymers modified by chemical after-treatment with organic compounds containing oxygen containing a hydroxy group
    • C08G65/3314Polymers modified by chemical after-treatment with organic compounds containing oxygen containing a hydroxy group cyclic
    • C08G65/3315Polymers modified by chemical after-treatment with organic compounds containing oxygen containing a hydroxy group cyclic aromatic
    • C08G65/3317Polymers modified by chemical after-treatment with organic compounds containing oxygen containing a hydroxy group cyclic aromatic phenolic
    • CCHEMISTRY; METALLURGY
    • C08ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08GMACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
    • C08G69/00Macromolecular compounds obtained by reactions forming a carboxylic amide link in the main chain of the macromolecule
    • C08G69/44Polyester-amides
    • CCHEMISTRY; METALLURGY
    • C08ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08KUse of inorganic or non-macromolecular organic substances as compounding ingredients
    • C08K5/00Use of organic ingredients
    • C08K5/04Oxygen-containing compounds
    • C08K5/13Phenols; Phenolates
    • CCHEMISTRY; METALLURGY
    • C08ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08KUse of inorganic or non-macromolecular organic substances as compounding ingredients
    • C08K5/00Use of organic ingredients
    • C08K5/16Nitrogen-containing compounds
    • C08K5/20Carboxylic acid amides
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/20Pills, tablets, discs, rods
    • A61K9/2004Excipients; Inactive ingredients
    • A61K9/2022Organic macromolecular compounds
    • A61K9/2031Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyethylene oxide, poloxamers
    • A61K9/204Polyesters, e.g. poly(lactide-co-glycolide)
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices

Abstract

Iodinated and/or brominated derivatives of aromatic dihydroxy monomers are prepared and polymerized to form radio-opaque polymers. The monomers may also be copolymerized with other dihydroxy monomers. The iodinated and brominated aromatic dihydroxy monomers can be employed as radio-opacifying, biocompatible non-toxic additives for other polymeric biomaterials. Radio-opaque medical implants and drug delivery devices for implantation prepared from the polymers of the present invention are also disclosed.

Claims

AMENDED CLAIMS
[received by the International Bureau on 25 May 1999 (25.05.99); original claims 16-18 amended; new claims 92 and 93 added; remaining claims unchanged (2 pages)]
O
R« — C— NH — CH— RQ I c=o
R0 is selected from the group consisting of -CH=CH-, -CHJ,-CHJ2- and (-CH2-)m, R, is selected from the group consisting of -CH=CH-, -CHJrCHJ2- and (-CH2-)a, wherein a and m are independently between 0 and 8, inclusive; and J, and J2 are independently Br or I; and Z is selected from the group consisting of hydrogen, a free carboxylic acid group, and esters and amides thereof, said esters and amides being selected from the group consisting of straight and branched alkyl and alkylaryl groups containing up to 18 carbon atoms and derivatives of biologically and pharmaceutically active compounds.
17. The polymer of claim 16, characterized in that g is greater than 0 and R]2 has a structure selected from the group consisting of:
O II
R4 -C— NH -CH— o c=o
wherein R^ is -CH=CH- or (-CH2-)ra and R-, is -CH=CH-, or (-CH2-)a, wherein a and m are independently between 0 and 8, inclusive; and Z is selected from the group consisting of hydrogen, a free carboxylic acid group, and esters and amides thereof said esters and amides being selected from the group consisting of straight and branched alkyl and alkylaryl groups containing up to 18 carbon atoms and derivatives of biologically and phaπnaceutically active compounds.
18. The polymer of claim 17, characterized in that R, has the structure:
0
II
- CH2)i5C-NH -CH CH27r— z
92. A radio-opaque biocompatible polymer comprising monomeric repeating units substituted with at least one bromine or iodine atom, and having the structure:
Figure imgf000004_0001
wherein each Xj and X2 are independently iodine or bromine, each Yl and Y2 are independently 0, 1 or 2, and R, is an alkyl, aryl or alkylaryl group containing up to 18 carbon atoms.
93. A radio-opaque biocompatible polymer comprising monomeric repeating units substituted with at least one bromine or iodine atom and having the structure:
Figure imgf000004_0002
wherein each X2 is independently iodine or bromine, each Y2 is 0, 1 or 2, each Rs and R6 are independently selected from the group consisting of hydrogen, bromine, iodine and straight and branched alkyl groups having up to 18 carbon atoms; Q is (-CH2-)d-, -CH=CH- or (-CHJ,-CHJr) and R15 is (-CH2-)m, -CH=CH- or (-CHJ,-CHJ2), wherein each J, and J2 are independently bromine or iodine and d and m are independently between 0 and 8, inclusive; and each Z is independently selected from the group consisting of hydrogen, a free carboxylic acid group or an ester or amide thereof, said ester or amide comprising straight and branched alkyl and alkylaryl groups containing up to 18 carbon atoms and derivatives of biologically and pharmaceutically active compounds.
PCT/US1998/023777 1997-11-07 1998-11-06 Radio-opaque polymer biomaterials WO1999024391A1 (en)

Priority Applications (11)

Application Number Priority Date Filing Date Title
JP2000520405A JP4465105B2 (en) 1997-11-07 1998-11-06 Radiopaque polymer biocompatible material
AT98959390T ATE307110T1 (en) 1997-11-07 1998-11-06 RADIATION TRANSPARENT POLYMERIC BIOMATERIAL
US09/554,027 US6475477B1 (en) 1997-11-07 1998-11-06 Radio-opaque polymer biomaterials
EP98959390A EP1036057B1 (en) 1997-11-07 1998-11-06 Radio-opaque polymer biomaterials
AU15199/99A AU737151B2 (en) 1997-11-07 1998-11-06 Radio-opaque polymeric biomaterials government license rights
CA002308721A CA2308721C (en) 1997-11-07 1998-11-06 Radio-opaque polymer biomaterials
DE69831973T DE69831973T2 (en) 1997-11-07 1998-11-06 RADIATION PERMEABLE POLYMERIC BIOMATERIAL
US10/691,750 US7056493B2 (en) 1997-11-07 2003-10-23 Radio-opaque polymer biomaterials
US11/024,355 US7250154B2 (en) 1997-11-07 2004-12-28 Radio-opaque polymeric biomaterials
US11/418,943 US20060204440A1 (en) 1997-11-07 2006-05-05 Radio-opaque polymeric biomaterials
US11/933,780 US20080107709A1 (en) 1997-11-07 2007-11-01 Radio-opaque polymeric biomaterials

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US6490597P 1997-11-07 1997-11-07
US60/064,905 1997-11-07

Related Child Applications (3)

Application Number Title Priority Date Filing Date
US09/554,027 A-371-Of-International US6475477B1 (en) 1997-11-07 1998-11-06 Radio-opaque polymer biomaterials
US09554027 A-371-Of-International 1998-11-06
US10/288,076 Division US6852308B2 (en) 1997-11-07 2002-11-05 Radio-opaque polymeric biomaterials

Publications (2)

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WO1999024391A1 WO1999024391A1 (en) 1999-05-20
WO1999024391B1 true WO1999024391B1 (en) 1999-07-15

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PCT/US1998/023777 WO1999024391A1 (en) 1997-11-07 1998-11-06 Radio-opaque polymer biomaterials
PCT/US1998/023737 WO1999024490A1 (en) 1997-11-07 1998-11-06 Strictly alternating poly(alkylene oxide ether) copolymers

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US (9) US6475477B1 (en)
EP (3) EP1028991B1 (en)
JP (3) JP4465105B2 (en)
AT (3) ATE273341T1 (en)
AU (2) AU737151B2 (en)
CA (3) CA2308721C (en)
DE (3) DE69831973T2 (en)
ES (1) ES2226191T3 (en)
WO (2) WO1999024391A1 (en)

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