WO2015123713A1 - Polymère hybride de polyvinylpyrrolidone ayant un squelette greffé avec de la polyvinylpyrrolidone - Google Patents

Polymère hybride de polyvinylpyrrolidone ayant un squelette greffé avec de la polyvinylpyrrolidone Download PDF

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Publication number
WO2015123713A1
WO2015123713A1 PCT/AT2015/050049 AT2015050049W WO2015123713A1 WO 2015123713 A1 WO2015123713 A1 WO 2015123713A1 AT 2015050049 W AT2015050049 W AT 2015050049W WO 2015123713 A1 WO2015123713 A1 WO 2015123713A1
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WO
WIPO (PCT)
Prior art keywords
polyvinylpyrrolidone
hybrid polymer
grafted
cio
polyphosphazene
Prior art date
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.)
Ceased
Application number
PCT/AT2015/050049
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German (de)
English (en)
Inventor
Ian Teasdale
Oliver BRÜGGEMANN
Sandra ROTHEMUND
Helena HENKE
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Universitaet Linz
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Universitaet Linz
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Publication date
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Publication of WO2015123713A1 publication Critical patent/WO2015123713A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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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
    • C08G81/00—Macromolecular compounds obtained by interreacting polymers in the absence of monomers, e.g. block polymers
    • C08G81/02—Macromolecular compounds obtained by interreacting polymers in the absence of monomers, e.g. block polymers at least one of the polymers being obtained by reactions involving only carbon-to-carbon unsaturated bonds
    • C08G81/024—Block or graft polymers containing sequences of polymers of C08C or C08F and of polymers of C08G
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
    • C08F283/00—Macromolecular compounds obtained by polymerising monomers on to polymers provided for in subclass C08G
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
    • C08F26/00—Homopolymers and copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by a single or double bond to nitrogen or by a heterocyclic ring containing nitrogen
    • C08F26/06—Homopolymers and copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by a single or double bond to nitrogen or by a heterocyclic ring containing nitrogen by a heterocyclic ring containing nitrogen
    • C08F26/10—N-Vinyl-pyrrolidone
    • 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
    • C08G79/00—Macromolecular compounds obtained by reactions forming a linkage containing atoms other than silicon, sulfur, nitrogen, oxygen, and carbon with or without the latter elements in the main chain of the macromolecule
    • C08G79/02—Macromolecular compounds obtained by reactions forming a linkage containing atoms other than silicon, sulfur, nitrogen, oxygen, and carbon with or without the latter elements in the main chain of the macromolecule a linkage containing phosphorus
    • C08G79/025—Polyphosphazenes
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
    • C08L87/00—Compositions of unspecified macromolecular compounds, obtained otherwise than by polymerisation reactions only involving unsaturated carbon-to-carbon bonds
    • C08L87/005—Block or graft polymers not provided for in groups C08L1/00 - C08L85/04
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
    • C08F2438/00—Living radical polymerisation
    • C08F2438/03—Use of a di- or tri-thiocarbonylthio compound, e.g. di- or tri-thioester, di- or tri-thiocarbamate, or a xanthate as chain transfer agent, e.g . Reversible Addition Fragmentation chain Transfer [RAFT] or Macromolecular Design via Interchange of Xanthates [MADIX]

Definitions

  • the invention relates to a polyvinylpyrrolidone hybrid polymer having a polyvinylpyrrolidone grafted backbone.
  • Polyvinylpyrrolidone is mainly used in cosmetic and pharmaceutical fields, but is not biodegradable. As a result, high molecular weight polyvinylpyrrolidone is unsuitable for certain applications, such as the repeated intravenous administration of an active ingredient, and may also cause long-term biological and environmental problems. Although it is possible to use polyvinylpyrrolidone with a low molecular weight below the renal clearance (about 20 kDa), this limitation is unsatisfactory for many applications because higher molecular weights are essential to many polymeric carrier properties.
  • X is O, NH or S
  • the invention avoids the difficulties of the known polyvinylpyrrolidone hybrid polymers by polyvinylpyrrolidone oligomers having a low molecular weight (preferably between 200 and 2000 Da) are often bound to an inorganic backbone of polyphosphazene.
  • the resulting hybrid polymers have a predominant proportion of, for example, 95 to 99 mol% of polyvinylpyrrolidone, so that many of the chemical properties of the pure polyvinylpyrrolidone can be expected.
  • the backbone of polyphosphazene is hydrolytically unstable, whereby the hybrid polymers according to the invention are degraded in an aqueous environment to oligomeric polyvinylpyrrolidone and a pH neutral buffer solution of phosphates and ammonia.
  • polyphosphazene Since the polyphosphazene has two functional groups per repeat unit, it is not necessary to replace both functional groups by polyvinylpyrrolidone. This opens up a broad field for the use of Co substituents, which allow a large number of co-polymers with a wide range of degradation rates.
  • the basic structure of the hybrid polymers according to the invention offers the possibility of adjusting the rate of biodegradation of the polymers by incorporating a linker between the organic and inorganic components of the hybrid polymers.
  • the basis of these linkers can be advantageously formed by an amino acid.
  • CI 3 PNTMS can be subjected to a cationic living polymerization.
  • corresponding hybrid polymers product 3 are obtained according to the reaction scheme below.
  • n and m not only the molecular weight of the polymers but also the ratio of the organic and inorganic fractions to each other can be adjusted.
  • the upper limit for m and n will preferably be given as 1000, with particularly advantageous ratios resulting when the highest value is m 100 and n is 150. Even with low values of m, a high ratio of vinylpyrrolidone to phosphazene can be maintained, so that the many useful chemical properties of vinylpyrrolidone can be exploited.
  • the hydrolytic degradation rate of the hybrid polymers can be changed by incorporating a linker between the organic and inorganic components.
  • the insertion of an amino acid improves the rate of degradation of the hydrophilic phosphorases.
  • the insertion of a linker can be carried out, for example, according to the reaction scheme below and leads to the product 4.
  • R ' may preferably be selected from alanyl, valinyl, leucinyl, isoieucinyl, propynyl, phenylamino, tryptophanyl, ethioninyl, glycine I, serinyl, threoninyl, cysteine, tyrosinyl, aspartyl, glutainyl, aspartoyl, glutoyl, lysinyl However, it is not restricted to this group.
  • One of the two functional groups of the poly can also be substituted by a co-polymer according to the following reaction scheme, which also affects the rate of degradation.
  • co-polymers can be prepared, wherein, for example, a co-substitution with crosslinkable functional groups, such as vinyl, acryloyl and the like, leads to biodegradable hydrogels.
  • crosslinkable functional groups such as vinyl, acryloyl and the like
  • Exemplary Embodiment ⁇ -Hydroxylpolyvinylpyrrolidone (Product 1) Azobisisobutyronitrile (AIBN) (0.075 g, 0.45 mmol), CTA S-1-cyanoethyl-O-ethyl-xanthate (0.75 g, 3.96 mmol) and N-vinylpyrrolidone (NVP) (1.9.55 g, 175.9 mmol) were degassed with argon, heated and stirred in an oil bath at 60 ° C. for 6 h. The reaction mixture was then cooled to room temperature and precipitated in diethyl ether. The filtered white powder was dried under vacuum.
  • AIBN Azobisisobutyronitrile
  • CTA S-1-cyanoethyl-O-ethyl-xanthate (0.75 g, 3.96 mmol
  • N-vinylpyrrolidone N-vinylpyrrolidone
  • the monomer CI 3 P N-SiMe 3 (0.45 g, 2.01 mmol) and the initiator PCI 5 (0.02 g, 0.08 mmol) were dissolved in a glove box in CH 2 Cl 2 and at room temperature touched. After 12 h, the solvent was removed in vacuo. The resulting poly (dichlorophosphazene) was used for macromolecular substitution without further purification.
  • the poly (dichlorophosphazene) precursor (product 2) was prepared in a glove box at room temperature.
  • the monomer CI 3 PNSiMe 3 (0.05 g, 0.22 mmol) and the initiator PCI 5 (1, 9 mg, 0.01 mmol) were separately dissolved in water. dissolved free CH 2 Cl 2 and then added the mixtures and stirred overnight.
  • the deprotection of the polyvinylpyrrolidone-Val-boc polymer was reported in
  • the degradation behavior of the polymers was assessed by the determination of the inorganic phosphates by monitoring by UV-Vis spectroscopy.
  • the polymers were incubated in TRIS buffer (pH 7.4) or acidified H2O (pH 2, improved degradation conditions) at a concentration of 4 mg / ml at 37 ° C during the analysis time. Aliquots of the decomposing medium were taken at regular time intervals and mixed with a reagent solution of ammonium molybdate, ascorbic acid, sulfuric acid and potassium antimonyl tartrate. A UV-Vis analysis of the mixtures was carried out after 15 min of the incubation time at 885 nm.
  • the concentration of phosphates was from a Calculated calibration curve using potassium dihydrogen phosphate and given as a percentage of the theoretical amount of phosphate that can be solved by the polymer backbone. In the drawing, the percentage phosphate decrease over the degradation time is shown. Curve 1, drawn in full line, illustrates the degradation rate in a TRIS buffer at pH 7.4. In comparison, according to the dash-dotted curve 2, significantly improved mining conditions result when the hybrid polymer is exposed to pH 2 acidified water.

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  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Medicinal Chemistry (AREA)
  • Polymers & Plastics (AREA)
  • Organic Chemistry (AREA)
  • Addition Polymer Or Copolymer, Post-Treatments, Or Chemical Modifications (AREA)

Abstract

L'invention concerne le greffage d'une polyvinylpyrrolidone selon la formule structurelle (I) sur un polyphosphazène pour l'obtention d'un polymère hybride de polyvinylpyrrolidone ayant un squelette greffé avec de la polyvinylpyrrolidone.
PCT/AT2015/050049 2014-02-24 2015-02-23 Polymère hybride de polyvinylpyrrolidone ayant un squelette greffé avec de la polyvinylpyrrolidone Ceased WO2015123713A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
ATA50136/2014 2014-02-24
ATA50136/2014A AT515480B1 (de) 2014-02-24 2014-02-24 Polyvinylpyrrolidon-Hybridpolymer mit einem mit Polyvinylpyrrolidon gepfropften Rückgrat

Publications (1)

Publication Number Publication Date
WO2015123713A1 true WO2015123713A1 (fr) 2015-08-27

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Application Number Title Priority Date Filing Date
PCT/AT2015/050049 Ceased WO2015123713A1 (fr) 2014-02-24 2015-02-23 Polymère hybride de polyvinylpyrrolidone ayant un squelette greffé avec de la polyvinylpyrrolidone

Country Status (2)

Country Link
AT (1) AT515480B1 (fr)
WO (1) WO2015123713A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN113739524A (zh) * 2021-08-04 2021-12-03 徐州恒世食品有限公司 一种食品添加剂烘干装置

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2510128A1 (fr) * 1981-07-21 1983-01-28 Inst Mondial Phosphate Nouvelles compositions de polymeres ignifuges et leurs procedes de preparation
WO2006113274A1 (fr) * 2005-04-15 2006-10-26 Parallel Solutions, Inc. Polyphosphazenes biodegradables contenant des groupes pyrrolidone lateraux
US20140030320A1 (en) * 2002-11-21 2014-01-30 Alexander Andrianov Biodegradable Polyphosphazenes Containing Pyrrolidone Side Groups

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP3541894B2 (ja) * 1994-02-18 2004-07-14 日本化薬株式会社 温度応答型ハイドロゲル
AU6366700A (en) * 1999-07-21 2001-02-13 Penn State Research Foundation, The Polyphosphazene polymers

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2510128A1 (fr) * 1981-07-21 1983-01-28 Inst Mondial Phosphate Nouvelles compositions de polymeres ignifuges et leurs procedes de preparation
US20140030320A1 (en) * 2002-11-21 2014-01-30 Alexander Andrianov Biodegradable Polyphosphazenes Containing Pyrrolidone Side Groups
WO2006113274A1 (fr) * 2005-04-15 2006-10-26 Parallel Solutions, Inc. Polyphosphazenes biodegradables contenant des groupes pyrrolidone lateraux

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN113739524A (zh) * 2021-08-04 2021-12-03 徐州恒世食品有限公司 一种食品添加剂烘干装置

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AT515480A1 (de) 2015-09-15
AT515480B1 (de) 2017-12-15

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