WO2012066194A2 - Procédé de préparation de polymères étoilés - Google Patents
Procédé de préparation de polymères étoilés Download PDFInfo
- Publication number
- WO2012066194A2 WO2012066194A2 PCT/FR2011/000601 FR2011000601W WO2012066194A2 WO 2012066194 A2 WO2012066194 A2 WO 2012066194A2 FR 2011000601 W FR2011000601 W FR 2011000601W WO 2012066194 A2 WO2012066194 A2 WO 2012066194A2
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- initiator
- preparation
- star polymers
- lactide
- monomer
- Prior art date
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G63/00—Macromolecular compounds obtained by reactions forming a carboxylic ester link in the main chain of the macromolecule
- C08G63/78—Preparation processes
- C08G63/82—Preparation processes characterised by the catalyst used
- C08G63/823—Preparation processes characterised by the catalyst used for the preparation of polylactones or polylactides
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G63/00—Macromolecular compounds obtained by reactions forming a carboxylic ester link in the main chain of the macromolecule
- C08G63/02—Polyesters derived from hydroxycarboxylic acids or from polycarboxylic acids and polyhydroxy compounds
- C08G63/06—Polyesters derived from hydroxycarboxylic acids or from polycarboxylic acids and polyhydroxy compounds derived from hydroxycarboxylic acids
- C08G63/08—Lactones or lactides
Definitions
- the subject of the present application is a process for preparing star-shaped polymers based on lactide and / or glycolide. This method is easily controllable and has a better efficiency than the methods of the prior art. It is particularly interesting in that the polymers obtained are functionalized on all branches of the star, even in the case of oligomers.
- branched polymers including star polymers, dendrimers and hyperbranched polymers, have been the subject of numerous studies, due to their interesting rheological and mechanical properties.
- star-shaped polymers or star-architecture polymers, can be used in the administration of active principles and have interesting release.
- This type of polymer is generally prepared from polyol initiators having n alcohol functions to lead to n-arm stars.
- the star polymers have glass transition temperatures, as well as vitreous viscosity, different from their linear equivalents. The same is true of their crystallinity - and therefore their melting temperature - which is also different from their linear equivalents.
- high molecular weight polymers have a lower glass transition temperature and melting temperature than their linear equivalents.
- the crystalline phase remains of the same nature in both architectures.
- a biodegradable star polymer (eg, PLGA) will have an initial rate of degradation much faster than its linear equivalent of the same mass. Indeed, it has been shown that by chemical or enzymatic hydrolysis, the first cleavages of ester bonds are carried out at the heart of the star, close to the initiator, thus releasing linear polymers of lower molecular weights. Thus, the rate of release and degradation is to be correlated with the structure of the polymer matrix.
- Examples of the preparation of star-shaped polyesters via organic catalysts concern monomers other than lactide, such as ⁇ -valerolactone or ⁇ -caprolactone (F. Sanda, H. Sanada, Y. Shibasaki, T. Endo, Macromolecules 2002, 35, 680; PV Persson, J. Casas, T. Iversen, A. Cordova, Macromolecules 2006, 39, 2819 and F. Zeng, H. Lee, M. Chidiac, C. Allen, Biomacromolecules 2005. , 6, 2140). With the catalysts used (fumaric or lactic acid) the reaction temperatures required are relatively high (of the order of 90 ° C.).
- organocatalyst ring opening of lactide are all based on macroinitiators.
- catalytic system for the synthesis of low molecular weight oligomers from a polyol, ensuring full functionalization of the arms.
- the applicant has developed a new non-metallic process, easily controllable and having a better efficiency than the processes of the prior art in the case of oligomers.
- the subject of the invention is therefore a method for preparing star polymers based on a lactide monomer and a glycolide monomer or on a lactide monomer, by ring opening in the presence of a catalyst, in which: the catalyst has the formula Wherein R is a haloalkyl -C 6;
- the initiator is a polyol comprising from 3 to 6 hydroxyl functions.
- the monomer is lactide.
- the polymers are prepared based on a lactide monomer and a glycolide monomer.
- the reaction takes place in an organic solvent, even more preferably in a halogenated or aromatic solvent.
- the solvent is a halogenated solvent, preferably the solvent is dichloromethane.
- the initiator is a polyol comprising from 3 to 4 hydroxyl functions.
- the initiator is glycerol.
- the catalyst is trifluoromethanesulfonic acid.
- the reaction temperature is 0 to 150 ° C, more preferably 20 to 45 ° C.
- the initial monomer concentration / OH concentration ratio of the initiator is 200/1 to 1/1.
- the initial monomer concentration / OH concentration ratio of the initiator is from 100/1 to 2/1.
- the initial monomer concentration / OH concentration ratio of the initiator is from 20/1 to 4/1.
- the initial catalyst concentration / OH concentration ratio of the initiator is from 0.1 to 20.
- the initial catalyst concentration / OH concentration ratio of the initiator is from 0.2 to 10.
- the initial catalyst concentration / OH concentration ratio of the initiator is from 0.3 to 10. 6.
- the subject of the invention is therefore a process for preparing star-shaped polymers based on lactide and / or glycolide.
- star polymer is meant a polymer having a single point of branching from which emanate several linear chains.
- the polymerization reaction is of the ring-opening type.
- the ring opening polymerization is an addition polymerization. It can be schematized
- the reaction is carried out from a lactide monomer and a glycolide monomer, or from a lactide monomer alone.
- the monomer is lactide.
- the reaction is a co-polymerization and the reaction is carried out from lactide and glycolide.
- R represents a haloalkyl.
- haloalkyl is meant an alkyl radical substituted with one or more halogen atoms.
- the alkyl radical comprises from 1 to 6 carbon atoms, preferably from 1 to 4 carbon atoms.
- the halogen atom is selected from F, Cl, Br and I.
- the haloalkyl is C 2 F 6 or CF 3 .
- the haloalkyl is CF 3 .
- the initiator of the reaction is a polyol comprising from 3 to 6 hydroxyl functions, that is to say that the initiator is an organic molecule comprising from 3 to 6 -OH functions.
- the polyol as defined in the present invention may be an aliphatic or cyclic carbon chain.
- the polyol may also contain other organic functions, for example one or more aldehyde and / or ketone functions.
- the polyol may be chosen from glycerol, trimethylolethane, trimethylolpropane, pentaerythritol, dipentaerythritol, inositol, xylitol, mannitol, sorbitol, erythrose, threose, arabinose and ribose.
- the initiator is pentaerythritol, dipentaerythritol, glycerol, trimethylolethane, trimethylolpropane, or sorbitol. More preferably, the initiator is glycerol.
- solvent herein means a single solvent or a mixture of solvents.
- the solvent is chosen such that the polymer formed therein is soluble.
- the solvent is selected from halogenated solvents and aromatic solvents.
- the solvent is selected from dichloromethane, dichloroethane and toluene.
- the solvent is dichloromethane.
- the reaction is carried out at a temperature between room temperature, i.e. about 25 ° C, and the boiling temperature of the selected solvent.
- the reaction temperature is chosen to be lower than the degradation temperature of the polymer formed.
- the temperature is 0 to 150 ° C.
- the temperature is 10 to 90 ° C. More preferably, the temperature is 20 to 45 ° C, preferably 20 to 30 ° C. for example, the reaction is carried out at room temperature.
- the reaction is stopped once the desired degree of polymerization has been achieved.
- the reaction is stopped when the consumption of the initial monomer is 90 to 100%.
- the reaction is stopped when the consumption of the initial monomer is greater than 94%.
- the reaction is stopped by quenching.
- the reaction is stopped by adding a based.
- the polymerization reaction is stopped by adding a basic resin, such as, for example, Amberlyst TM A21.
- the monomer concentration initial ratio to the OH concentration of the initiator is 200/1 to 1/1, more preferably 100/1 to 3/1, more preferably 20 / 1 to 4/1.
- the ratio is 8/1 to 6/1.
- the initial concentration ratio of catalyst to OH concentration concentration of the initiator is from 0.1 to 20, more preferably from 0.2 to 10, even more preferably from 0.2 to 6.
- the process according to the invention has many advantages. In particular, the process is easily controllable. It is more efficient than the processes of the prior art.
- the polymers obtained are functionalized on all the branches of the star. This is also true when synthesizing oligomers.
- oligomer is meant a small polymer, preferably having a molar mass of less than 2000 g / mol.
- TMP trimethylolpropane
- PET pentaerythritol
- glycerol is distilled.
- the catalyst is neutralized with Amberlyst TM A21 basic resin.
- the polymers are precipitated in a CH 2 Cl 2 / heptane mixture and then dried under vacuum on a rotary evaporator for 48 h.
- Example 5 Polymer primed with glycerol in the presence of 4.5 equivalents of D, L-lactide.
- trimethylolethane was chosen as the initiator.
- trimethylolethane is used after sublimation.
- Lactide is used either in racemic (L) or enantiopure (L) form.
- the length of the polymer is dependent on the initial ratio [Monomer M] o / [Primer I] 0 . Different [M] o / [I] o ratios are set for each polymerization in order to obtain polymers of various masses.
- a PLGA copolymer of star form and lactide / glycolide ratio 80/20 is synthesized from trimethylolethane.
- Example 12 Synthesis of a star PLA in toluene at 80 ° C.
- toluene is used as a solvent after distillation and the reaction mixture is heated to 80 ° C.
- the dipentaerythritol is first dried under vacuum in the presence of P 2 0 5 .
- the polymerizations are carried out at room temperature.
- the catalyst is neutralized by treatment with the basic Amberlyst A21 resin.
- the polymer obtained is well controlled: the DP R MN per arm is close to the theoretical DP (equal to 3) and by 1H NMR spectroscopy, the integration for 12H CH 2 -0-PLA coupled with the absence of a signal around 3.5 ppm (characteristic region of the CH 2 -OH of the initiator) makes it possible to affirm that the priming on all the alcohols of dipentaerythritol is complete.
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Medicinal Chemistry (AREA)
- Polymers & Plastics (AREA)
- Organic Chemistry (AREA)
- Polyesters Or Polycarbonates (AREA)
- Materials For Medical Uses (AREA)
- Polyethers (AREA)
Abstract
Description
Claims
Priority Applications (9)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
RU2013127292/04A RU2589876C2 (ru) | 2010-11-15 | 2011-11-14 | Способ получения звездообразных полимеров |
EP11841514.0A EP2640768B1 (fr) | 2010-11-15 | 2011-11-14 | Procédé de préparation de polymères étoilés |
DK11841514.0T DK2640768T3 (en) | 2010-11-15 | 2011-11-14 | Process for the preparation of star polymers |
ES11841514.0T ES2532707T3 (es) | 2010-11-15 | 2011-11-14 | Procedimiento de preparación de polímeros en estrella |
CN2011800548839A CN103210016A (zh) | 2010-11-15 | 2011-11-14 | 制备星形聚合物的方法 |
US13/885,663 US20130237682A1 (en) | 2010-11-15 | 2011-11-14 | Method for preparing star polymers |
JP2013538249A JP5990179B2 (ja) | 2010-11-15 | 2011-11-14 | スターポリマーの製造方法 |
PL11841514T PL2640768T3 (pl) | 2010-11-15 | 2011-11-14 | Sposób wytwarzania polimerów gwiaździstych |
HK14102082.9A HK1189013A1 (en) | 2010-11-15 | 2014-03-03 | Method for preparing star polymers |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
FR10/04427 | 2010-11-15 | ||
FR1004427A FR2967415B1 (fr) | 2010-11-15 | 2010-11-15 | Procede de preparation de polymeres etoiles |
Publications (2)
Publication Number | Publication Date |
---|---|
WO2012066194A2 true WO2012066194A2 (fr) | 2012-05-24 |
WO2012066194A3 WO2012066194A3 (fr) | 2013-03-28 |
Family
ID=43726548
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/FR2011/000601 WO2012066194A2 (fr) | 2010-11-15 | 2011-11-14 | Procédé de préparation de polymères étoilés |
Country Status (12)
Country | Link |
---|---|
US (1) | US20130237682A1 (fr) |
EP (1) | EP2640768B1 (fr) |
JP (1) | JP5990179B2 (fr) |
CN (2) | CN107641195A (fr) |
DK (1) | DK2640768T3 (fr) |
ES (1) | ES2532707T3 (fr) |
FR (1) | FR2967415B1 (fr) |
HK (1) | HK1189013A1 (fr) |
PL (1) | PL2640768T3 (fr) |
PT (1) | PT2640768E (fr) |
RU (1) | RU2589876C2 (fr) |
WO (1) | WO2012066194A2 (fr) |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR3002537A1 (fr) * | 2013-02-26 | 2014-08-29 | Ipsen Pharma | Nouveau procede de purification de polyesters |
EP3603650A1 (fr) | 2018-08-01 | 2020-02-05 | Edix O Sarl | Compositions injectables et a duree d'action prolongee pour leur utilisation dans le traitement de maladies de l'ongle et/ou pour accelerer la croissance de l'ongle |
WO2020025683A1 (fr) | 2018-08-01 | 2020-02-06 | Edix-O Sarl | Compositions injectables a duree d'action prolongee pour leur utilisation dans le traitement de maladie de l'ongle et/ou pour accelerer la croissance de l'ongle |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CZ305046B6 (cs) * | 2013-12-05 | 2015-04-08 | Vysoké Učení Technické V Brně | Způsob přípravy blokového kopolymeru |
Family Cites Families (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR970002523B1 (en) * | 1993-04-24 | 1997-03-05 | Korea Inst Sci & Tech | Biodegradable polylactic acid having improved properties and method for manufacturing the same |
SE503559C2 (sv) * | 1994-09-08 | 1996-07-08 | Inst Polymerutveckling Ab | Strålningshärdbar hypergrenad polyester, förfarande för dess framställning samt dess användning |
JP3669819B2 (ja) * | 1997-07-10 | 2005-07-13 | 三井化学株式会社 | 分解性共重合体及びその製造方法 |
JP3483753B2 (ja) * | 1997-12-29 | 2004-01-06 | タキロン株式会社 | 生体内分解吸収性可塑性粘着物 |
JP4139516B2 (ja) * | 1998-04-28 | 2008-08-27 | 三井化学株式会社 | ポリエステルの製造方法 |
US7151155B2 (en) * | 2001-04-17 | 2006-12-19 | Union Carbide Chemicals & Plastics Technology Corporation | Copolymers of cyclic esters and cyclic formals |
EP1440992A1 (fr) * | 2003-01-21 | 2004-07-28 | Société de Conseils de Recherches et d'Applications Scientifiques ( S.C.R.A.S.) | Système catalytique de (co)polymérisation du lactide et du glycolide |
-
2010
- 2010-11-15 FR FR1004427A patent/FR2967415B1/fr not_active Expired - Fee Related
-
2011
- 2011-11-14 DK DK11841514.0T patent/DK2640768T3/en active
- 2011-11-14 CN CN201710886309.9A patent/CN107641195A/zh active Pending
- 2011-11-14 EP EP11841514.0A patent/EP2640768B1/fr not_active Not-in-force
- 2011-11-14 WO PCT/FR2011/000601 patent/WO2012066194A2/fr active Application Filing
- 2011-11-14 CN CN2011800548839A patent/CN103210016A/zh active Pending
- 2011-11-14 PL PL11841514T patent/PL2640768T3/pl unknown
- 2011-11-14 RU RU2013127292/04A patent/RU2589876C2/ru active
- 2011-11-14 PT PT11841514T patent/PT2640768E/pt unknown
- 2011-11-14 ES ES11841514.0T patent/ES2532707T3/es active Active
- 2011-11-14 US US13/885,663 patent/US20130237682A1/en not_active Abandoned
- 2011-11-14 JP JP2013538249A patent/JP5990179B2/ja not_active Expired - Fee Related
-
2014
- 2014-03-03 HK HK14102082.9A patent/HK1189013A1/xx not_active IP Right Cessation
Non-Patent Citations (12)
Title |
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A. BREITENBACH; Y. X. LI; T. KISSEL, JOURNAL OF CONTROLLED RELEASE, vol. 64, 2000, pages 167 |
A. FINNE; A.-C. ALBERTSSON, BIOMACROMOLECULES, vol. 3, 2002, pages 684 |
ADV. MATER., vol. 8, 1996, pages 305 |
CHEM. ENG. NEWS, vol. 79, no. 6, 2001, pages 30 |
CHEMOSPHERE, vol. 43, 2001, pages 49 |
F. SANDA; H. SANADA; Y. SHIBASAKI; T. ENDO, MACROMOLECULES, vol. 35, 2002, pages 680 |
F. ZENG; H. LEE; M. CHIDIAC; C. ALLEN, BIOMACROMOLECULES, vol. 6, 2005, pages 2140 |
H. R. KRICHELDORF; H. HACHMANN-THIESSEN; G. SCHWARZ, BIOMACROMOLECULES, vol. 5, 2004, pages 492 |
H.R. KRICHELDORF, POLYMER FOR ADVANCED TECHNOLOGIES, vol. 13, 2002, pages 969 |
I. ARVANITOYANNIS; A. NAKAYAMA; E. PSOMIADOU; N. KAWASAKI; N. YAMAMOTO, POLYMER, vol. 37, 1996, pages 651 |
K. NUMATA; R. K. SRIVASTAVA; A. FINNE-WISTRAND; A.-C. ALBERTSSON; Y. DOI; H. ABE, BIOMACROMOLECULES, vol. 8, 2007, pages 3115 |
P. V. PERSSON; J. CASAS; T. IVERSEN; A. CORDOVA, MACROMOLECULES, vol. 39, 2006, pages 2819 |
Cited By (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR3002537A1 (fr) * | 2013-02-26 | 2014-08-29 | Ipsen Pharma | Nouveau procede de purification de polyesters |
WO2014131747A1 (fr) * | 2013-02-26 | 2014-09-04 | Ipsen Pharma S.A.S. | Nouveau procédé de purification de polyesters |
AU2014222813B2 (en) * | 2013-02-26 | 2017-02-02 | Ipsen Pharma S.A.S. | Novel method for purifying polyesters |
CN105026458B (zh) * | 2013-02-26 | 2017-06-16 | 益普生制药股份有限公司 | 提纯聚酯的方法 |
EA030748B1 (ru) * | 2013-02-26 | 2018-09-28 | Ипсен Фарма С.А.С. | Новый способ очистки сложных полиэфиров |
EP3603650A1 (fr) | 2018-08-01 | 2020-02-05 | Edix O Sarl | Compositions injectables et a duree d'action prolongee pour leur utilisation dans le traitement de maladies de l'ongle et/ou pour accelerer la croissance de l'ongle |
WO2020025683A1 (fr) | 2018-08-01 | 2020-02-06 | Edix-O Sarl | Compositions injectables a duree d'action prolongee pour leur utilisation dans le traitement de maladie de l'ongle et/ou pour accelerer la croissance de l'ongle |
Also Published As
Publication number | Publication date |
---|---|
HK1189013A1 (en) | 2014-05-23 |
FR2967415A1 (fr) | 2012-05-18 |
WO2012066194A3 (fr) | 2013-03-28 |
JP5990179B2 (ja) | 2016-09-07 |
CN103210016A (zh) | 2013-07-17 |
DK2640768T3 (en) | 2015-03-02 |
PT2640768E (pt) | 2015-03-19 |
FR2967415B1 (fr) | 2012-11-30 |
PL2640768T3 (pl) | 2015-06-30 |
RU2013127292A (ru) | 2014-12-27 |
RU2589876C2 (ru) | 2016-07-10 |
EP2640768A2 (fr) | 2013-09-25 |
ES2532707T3 (es) | 2015-03-31 |
JP2013542305A (ja) | 2013-11-21 |
EP2640768B1 (fr) | 2015-01-07 |
US20130237682A1 (en) | 2013-09-12 |
CN107641195A (zh) | 2018-01-30 |
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