WO2012147069A1 - Procédé de préparation de nanoéponges de dextrines - Google Patents

Procédé de préparation de nanoéponges de dextrines Download PDF

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Publication number
WO2012147069A1
WO2012147069A1 PCT/IB2012/052144 IB2012052144W WO2012147069A1 WO 2012147069 A1 WO2012147069 A1 WO 2012147069A1 IB 2012052144 W IB2012052144 W IB 2012052144W WO 2012147069 A1 WO2012147069 A1 WO 2012147069A1
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WO
WIPO (PCT)
Prior art keywords
cross
solution
dextrin
nanosponge
linking agent
Prior art date
Application number
PCT/IB2012/052144
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English (en)
Inventor
Francesco Trotta
Pravin SHENDE
Miriam BIASIZZO
Original Assignee
Universita' Degli Studi Di Torino
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Publication date
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Publication of WO2012147069A1 publication Critical patent/WO2012147069A1/fr

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    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08B—POLYSACCHARIDES; DERIVATIVES THEREOF
    • C08B37/00—Preparation of polysaccharides not provided for in groups C08B1/00 - C08B35/00; Derivatives thereof
    • C08B37/0006—Homoglycans, i.e. polysaccharides having a main chain consisting of one single sugar, e.g. colominic acid
    • C08B37/0009—Homoglycans, i.e. polysaccharides having a main chain consisting of one single sugar, e.g. colominic acid alpha-D-Glucans, e.g. polydextrose, alternan, glycogen; (alpha-1,4)(alpha-1,6)-D-Glucans; (alpha-1,3)(alpha-1,4)-D-Glucans, e.g. isolichenan or nigeran; (alpha-1,4)-D-Glucans; (alpha-1,3)-D-Glucans, e.g. pseudonigeran; Derivatives thereof
    • C08B37/0012—Cyclodextrin [CD], e.g. cycle with 6 units (alpha), with 7 units (beta) and with 8 units (gamma), large-ring cyclodextrin or cycloamylose with 9 units or more; Derivatives thereof

Definitions

  • the present invention relates to a method for preparing dextrin nanosponges by means of interfacial cross-linking .
  • Dextrin nanosponges are polymers of dextrins, in particular cyclodextrins , obtained by means of cross-linking with appropriate cross-linking agents.
  • Cyclodextrins are non-reducing cyclic oligosaccharides constituted by 6-8 glucose molecules linked with a 1,4-a- glucosidic bond, which have a characteristic frustoconical structure.
  • the arrangement of the functional groups of glucose molecules is such that the surface of the molecule is polar, whereas the internal cavity is relatively lipophilic.
  • the lipophilic cavity bestows on cyclodextrins the capacity for forming stable inclusion complexes even in solution with organic molecules of a suitable polarity and dimension.
  • WO03/085002, WO06/002814, and WO09/003656 describe cyclodextrin-based polymers obtained by cross-linking with cross-linking agents and used as drug carriers or for removal of pollutant agents from water. Said polymers are by now commonly known as "nanosponges”.
  • the aim of the present invention is consequently to provide a new method for preparing dextrin nanosponges that will be free from the disadvantages of the methods according to the known art .
  • the above aim is achieved by the present invention in so far as it relates to a method for preparing dextrin nanosponges according to Claim 1 and to a nanosponge according to Claim
  • polyfunctional cross-linking agent a molecule having at least two reactive functional groups capable of creating a bond with different dextrin molecules.
  • water- immiscible organic solvent an organic solvent having a certain difference of polarity as compared to water.
  • the index of polarity of water is equal to 9
  • all the organic solvents having a difference of index of polarity with respect to that of water of at least 5.0 are considered water- immiscible .
  • reactive carbonyl group is meant a functional group characterized by a carbon atom linked with a double bond to an oxygen atom and with two simple bonds to activating groups such as halogens, imidazole, electronegative atoms.
  • nanosponge a highly cross-linked porous polymer obtained by polymerization of dextrins.
  • Figure la illustrates the results of the DSC thermal analysis for a nanosponge obtained by cross -linking of beta- cyclodextrin with carbonyl diimidazole in a ratio 1:8 according to the methods known to the art;
  • Figure lb illustrates the results of the DSC thermal analysis for a nanosponge obtained by cross -linking of beta- cyclodextrin with carbonyl diimidazole in a ratio 1:8 according to the method of the present invention
  • Figure 2a illustrates the results of the DSC thermal analysis for a nanosponge obtained by cross-linking of beta- cyclodextrin with hexamethylene diisocyanate in a ratio 1:4 according to the methods known to the art;
  • Figure 2b illustrates the results of the DSC thermal analysis for a nanosponge obtained by cross -linking of beta- cyclodextrin with hexamethylene diisocyanate in a ratio 1:4 according to the method of the present invention
  • FIG. 3a illustrates the results of the DSC thermal analysis for a nanosponge obtained by cross -linking of beta- cyclodextrin with hexamethylene diisocyanate in a ratio 1:8 according to the methods known to the art;
  • Figure 3b illustrates the results of the DSC thermal analysis for a nanosponge obtained by cross -linking of beta- cyclodextrin with hexamethylene diisocyanate in a ratio 1:8 according to the method of the present invention
  • FIG. 4 illustrates the results of the DSC thermal analysis for a nanosponge obtained by cross-linking of beta- cyclodextrin with hexamethylene diisocyanate in a ratio 1:2 according to the method of the present invention and not obtainable according to the methods known to the art;
  • FIG. 5a illustrates the results of the thermogravimetric analysis (TGA) for a nanosponge obtained by cross- linking of beta-cyclodextrin with carbonyl diimidazole in a ratio 1:8 according to the methods known to the art;
  • TGA thermogravimetric analysis
  • TGA thermogravimetric analysis
  • FIG. 6a illustrates the results of the thermogravimetric analysis (TGA) for a nanosponge obtained by cross- linking of beta-cyclodextrin with hexamethylene diisocyanate in a ratio 1 : 8 according to the methods known to the art ;
  • TGA thermogravimetric analysis
  • FIG. 7a illustrates the results of the thermogravimetric analysis (TGA) for a nanosponge obtained by cross- linking of beta-cyclodextrin with hexamethylene diisocyanate in a ratio 1:4 according to the methods known to the art;
  • TGA thermogravimetric analysis
  • FIG. 7b illustrates the results of the thermogravimetric analysis (TGA) for a nanosponge obtained by cross-linking of beta-cyclodextrin with hexamethylene diisocyanate in a ratio
  • FIG. 8 illustrates the results of the thermogravimetric analysis (TGA) for a nanosponge obtained by cross-linking of beta-cyclodextrin with hexamethylene diisocyanate in a ratio 1:2 according to the method of the present invention
  • Figure 9a illustrates the IR spectrum for a nanosponge obtained by cross-linking of beta-cyclodextrin with carbonyl diimidazole in a ratio 1:8 according to the methods known to the art ;
  • FIG. 9b illustrates the IR spectrum for a nanosponge obtained by cross-linking of beta-cyclodextrin with carbonyl diimidazole in a ratio 1:8 according to the method of the present invention
  • FIG. 10a illustrates the results of the thermogravimetric analysis (TGA) for a nanosponge obtained by cross-linking of beta-cyclodextrin with hexamethylene diisocyanate in a ratio 1:8 according to the methods known to the art;
  • TGA thermogravimetric analysis
  • Figure 10b illustrates the IR spectrum for a nanosponge obtained by cross-linking of beta-cyclodextrin with hexamethylene diisocyanate in a ratio 1:8 according to the method of the present invention
  • FIG. 11a illustrates the IR spectrum for a nanosponge obtained by cross-linking of beta-cyclodextrin with hexamethylene diisocyanate in a ratio 1:4 according to the methods known to the art;
  • FIG. lib illustrates the IR spectrum for a nanosponge obtained by cross-linking of beta-cyclodextrin with hexamethylene diisocyanate in a ratio 1:4 according to the method of the present invention
  • FIG. 12 illustrates the IR spectrum for a nanosponge obtained by cross-linking of beta-cyclodextrin with hexamethylene diisocyanate in a ratio 1:2 according to the method of the present invention.
  • Figure 13 illustrates a Raman spectrum of a nanosponge obtained by means of the method of the present invention as compared with that of a nanosponge obtained by means of the methods known to the art .
  • the method of the present invention is a method of interfacial polymerization in which the nanosponge is produced by precipitation at the interface between an organic phase and an aqueous phase that are immiscible with one another.
  • the aqueous phase is constituted by an aqueous solution of a dextrin having a pH equal to or higher than 10, in particular comprised between 12 and 13.
  • the aqueous solution is a solution of a strong inorganic base, in particular a base of alkali metals or of alkaline-earth metals.
  • the base preferably used is potassium hydroxide.
  • linear dextrins and cyclodextrins can be used, in particular, natural cyclodextrins and their derivatives, and more in particular, beta-cyclodextrins .
  • the organic phase is, instead, constituted by an organic solution obtained by dissolving a cross-linking agent in an organic solvent, in particular chosen in the group constituted by methylene chloride, butanone, hexane, methyl isobutyl ketone, cyclohexane, carbon tetrachloride, methyl t-butyl ether, 1, 2-dichloroethane, ethyl acetate, and chloroform.
  • an organic solvent in particular chosen in the group constituted by methylene chloride, butanone, hexane, methyl isobutyl ketone, cyclohexane, carbon tetrachloride, methyl t-butyl ether, 1, 2-dichloroethane, ethyl acetate, and chloroform.
  • the polyfunctional cross-linking agent is a compound comprising a compound chosen in the group constituted by compounds comprising at least one reactive carbonyl group and epichlorohydrin, and in particular selected in the group constituted by carbonyl diimidazole, triphosgene, diphenyl carbonate, pyromellitic anhydride, epichlorohydrin, di- and polyisocyanates , and chlorides of carboxylic acids, more in particular carbonyl diimidazole and hexamethylene diisocyanate .
  • the aqueous dextrin solution and the organic solution of cross-linking agent are set in close contact and possibly stirred so as to increase the surface of contact also through the use of ultrasound.
  • the method of the present invention does not require the use of a surfactant in solution.
  • the method according to the invention unlike the methods known to the art for preparing dextrin nanosponges, does not require the use of anhydrous dextrins and of extractions for a subsequent purification. This method moreover enables nanoparticles to be obtained without the use of processes of a mechanical type, enables a reduction in the amount of solvents used, a reduction in the energy used, and is very fast.
  • thermogravimetric analysis TGA
  • DSC differential- scanning-calorimetry
  • a nanosponge is provided, which can be obtained with the method described above.
  • beta-cyclodextrin 1.135 grams of beta-cyclodextrin were dissolved completely in 20 mL of an 0.1-M aqueous solution of potassium hydroxide under magnetic agitation or by means of a sonicator.
  • the dextrin solution was added to the CDI solution under continuous agitation for 30 minutes.
  • the precipitate was washed with distilled water and centrifuged at 3000 rpm for 15 minutes.
  • the filtrate was filtered in vacuum conditions with distilled water and then with pure ethanol to remove the material that had possibly not reacted.
  • the filtrate was collected and dried in vacuum conditions to obtain the nanosponge .
  • nanosponges were prepared also with alpha-cyclodextrin and gamma-eyelodextrin, according to what appears in Table 1.
  • PMDA pyromellitic anhydride
  • TPh triphosgene
  • CDI carbonyl diimidazole
  • SSC sebacoyl chloride
  • DCM dichloromethane
  • DPC diphenyl carbonate
  • CD cyclodextrin
  • TDI toluene diisocyanate
  • DMC dimethyl carbonate
  • HDI hexamethylene diisocyanate.
  • the FTIRs show small differences in the signals, whereby it may be stated that the main bonds are the same in the nanosponges obtained with interfacial polymerization and those obtained with the methods known to the art.
  • the fine structure appears significantly different, as a demonstration of the different interactions present and as a confirmation of what was already observed with the thermal analyses .
  • the so-called Boson Peak in the Raman spectra ( Figure 13) is located at approximately 28-29 cm "1 in the nanosponges obtained with the method according to the invention, a value that is a little higher than the average value of 26 cm "1 obtained for nanosponges synthesized according to the methods known to the art.
  • this experimental observation shows the peculiar and different molecular structure of the nanosponges according to the invention as compared to those already known.

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  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Biochemistry (AREA)
  • Molecular Biology (AREA)
  • Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Materials Engineering (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Medicinal Chemistry (AREA)
  • Polymers & Plastics (AREA)
  • Organic Chemistry (AREA)
  • Inorganic Compounds Of Heavy Metals (AREA)
  • Polysaccharides And Polysaccharide Derivatives (AREA)

Abstract

La présente invention concerne un procédé de préparation de nanoéponges de dextrines comprenant les étapes consistant à dissoudre au moins une dextrine dans une solution aqueuse basique ayant un pH supérieur ou égal à 10 afin de former une solution de dextrines, à dissoudre un agent de réticulation polyfonctionnel dans un solvant organique non miscible à l'eau afin d'obtenir une solution d'agent de réticulation, et à mettre la solution de dextrines en contact étroit avec la solution d'agent de réticulation afin de faire précipiter la nanoéponge. L'invention concerne en outre une nanoéponge qui peut être obtenue par le biais du procédé selon la présente invention.
PCT/IB2012/052144 2011-04-28 2012-04-30 Procédé de préparation de nanoéponges de dextrines WO2012147069A1 (fr)

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IT000372A ITTO20110372A1 (it) 2011-04-28 2011-04-28 Metodo per la preparazione di nanospugne di destrine
ITTO2011A000372 2011-04-28

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Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ITBO20120710A1 (it) * 2012-12-28 2014-06-29 Univ Degli Studi Torino Sistema di veicolazione per l'insulina
ITTO20130831A1 (it) * 2013-10-15 2015-04-16 Univ Degli Studi Torino Nanospugne ciclodestriniche per applicazione nel settore del ritardo alla fiamma di materiali polimerici
WO2016004974A1 (fr) * 2014-07-07 2016-01-14 Roquette Italia S.P.A. Polymère à base d'une maltodextrine pour l'encapsulation de composés organiques
CN108651819A (zh) * 2018-05-18 2018-10-16 南昌大学 一种稳定态全谷物超微粉速食粉的制备方法
EP3556779A1 (fr) 2018-04-20 2019-10-23 Roquette Freres Polymères à base d'amidon réticulé pour administration de médicaments
IT201900016532A1 (it) 2019-09-17 2021-03-17 Francesco Trotta Processo per la preparazione di una nanospugna
CN112552535A (zh) * 2015-04-20 2021-03-26 康奈尔大学 多孔环糊精聚合材料及其制备和使用方法

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WO1998022197A1 (fr) * 1996-11-22 1998-05-28 The Regents Of The University Of California Matieres de separation en polymeres de cyclodextrine
US6197757B1 (en) * 1998-07-09 2001-03-06 Coletica Particles, especially microparticles or nanoparticles, of crosslinked monosaccharides and oligosaccharides, processes for their preparation and cosmetic, pharmaceutical or food compositions in which they are present
WO2003085002A1 (fr) 2002-04-10 2003-10-16 Sea Marconi Technologies Di W. Tumiatti S.A.S Polymeres reticules a base de cyclodextrines destines a eliminer des agents polluants
WO2006002814A1 (fr) 2004-06-25 2006-01-12 Sea Marconi Technologies Di W. Tumiatti S.A.S. Synthese assistee par ultrasons de nanoeponges a base de cyclodextrine
WO2009003656A1 (fr) 2007-07-04 2009-01-08 Sea Marconi Technologies Di Vander Tumiatti S.A.S. Nano-éponges à base de cyclodextrine comme véhicule pour médicaments anti-tumoraux

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WO1998022197A1 (fr) * 1996-11-22 1998-05-28 The Regents Of The University Of California Matieres de separation en polymeres de cyclodextrine
US6197757B1 (en) * 1998-07-09 2001-03-06 Coletica Particles, especially microparticles or nanoparticles, of crosslinked monosaccharides and oligosaccharides, processes for their preparation and cosmetic, pharmaceutical or food compositions in which they are present
WO2003085002A1 (fr) 2002-04-10 2003-10-16 Sea Marconi Technologies Di W. Tumiatti S.A.S Polymeres reticules a base de cyclodextrines destines a eliminer des agents polluants
WO2006002814A1 (fr) 2004-06-25 2006-01-12 Sea Marconi Technologies Di W. Tumiatti S.A.S. Synthese assistee par ultrasons de nanoeponges a base de cyclodextrine
WO2009003656A1 (fr) 2007-07-04 2009-01-08 Sea Marconi Technologies Di Vander Tumiatti S.A.S. Nano-éponges à base de cyclodextrine comme véhicule pour médicaments anti-tumoraux

Cited By (22)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ITBO20120710A1 (it) * 2012-12-28 2014-06-29 Univ Degli Studi Torino Sistema di veicolazione per l'insulina
US9987614B2 (en) 2013-10-15 2018-06-05 Roquette Italia S.P.A. Process for preparing a microporous carbon material and its use as absorption product
ITTO20130831A1 (it) * 2013-10-15 2015-04-16 Univ Degli Studi Torino Nanospugne ciclodestriniche per applicazione nel settore del ritardo alla fiamma di materiali polimerici
WO2015055729A1 (fr) * 2013-10-15 2015-04-23 Roquette Italia S.P.A. Procédé de préparation d'un matériau de carbone microporeux et son utilisation en tant que produit d'absorption
CN105764927A (zh) * 2013-10-15 2016-07-13 罗盖特意大利公司 一种用于制备微孔碳材料的方法及其作为吸收产品的用途
JP2017500260A (ja) * 2013-10-15 2017-01-05 ロケット イタリア エス．ピー．エイ． ミクロポーラス炭素材料を調製するための方法および吸着物としてのその使用
CN105764927B (zh) * 2013-10-15 2019-03-26 罗盖特意大利公司 一种用于制备微孔碳材料的方法及其作为吸收产品的用途
CN106573992B (zh) * 2014-07-07 2021-03-09 罗盖特意大利公司 用于包封有机化合物的基于麦芽糖糊精的聚合物
JP2017523277A (ja) * 2014-07-07 2017-08-17 ロケット イタリア エス．ピー．エイ． 有機化合物をカプセル封入するための、マルトデキストリンをベースとするポリマー
US20170130052A1 (en) * 2014-07-07 2017-05-11 Roquette Italia S.P.A. A polymer based on a maltodextrin for encapsulating organic compounds
CN106573992A (zh) * 2014-07-07 2017-04-19 罗盖特意大利公司 用于包封有机化合物的基于麦芽糖糊精的聚合物
WO2016004974A1 (fr) * 2014-07-07 2016-01-14 Roquette Italia S.P.A. Polymère à base d'une maltodextrine pour l'encapsulation de composés organiques
CN112552535B (zh) * 2015-04-20 2024-02-20 康奈尔大学 多孔环糊精聚合材料及其制备和使用方法
CN112552535A (zh) * 2015-04-20 2021-03-26 康奈尔大学 多孔环糊精聚合材料及其制备和使用方法
KR20210018224A (ko) * 2018-04-20 2021-02-17 호케트프레르 약물 전달용 가교 전분계 고분자
WO2019202148A1 (fr) 2018-04-20 2019-10-24 Roquette Freres Polymères réticulés à base d'amidon pour administration de médicament
EP3556779A1 (fr) 2018-04-20 2019-10-23 Roquette Freres Polymères à base d'amidon réticulé pour administration de médicaments
US11440975B2 (en) 2018-04-20 2022-09-13 Roquette Freres Cross-linked starch-based polymers for drug-delivery
KR102479842B1 (ko) 2018-04-20 2022-12-20 호케트프레르 약물 전달용 가교 전분계 고분자
CN108651819A (zh) * 2018-05-18 2018-10-16 南昌大学 一种稳定态全谷物超微粉速食粉的制备方法
IT201900016532A1 (it) 2019-09-17 2021-03-17 Francesco Trotta Processo per la preparazione di una nanospugna
WO2021053039A1 (fr) 2019-09-17 2021-03-25 Francesco Trotta Procédé de préparation d'une nanoéponge

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