CN105646890A - Chemical crosslinked pH value responsive multi-arm polymer and nano-porous capsule - Google Patents
Chemical crosslinked pH value responsive multi-arm polymer and nano-porous capsule Download PDFInfo
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- CN105646890A CN105646890A CN201610133767.0A CN201610133767A CN105646890A CN 105646890 A CN105646890 A CN 105646890A CN 201610133767 A CN201610133767 A CN 201610133767A CN 105646890 A CN105646890 A CN 105646890A
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- 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
- C08G81/025—Block or graft polymers containing sequences of polymers of C08C or C08F and of polymers of C08G containing polyether sequences
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
- A61K9/127—Liposomes
- A61K9/1271—Non-conventional liposomes, e.g. PEGylated liposomes, liposomes coated with polymers
- A61K9/1273—Polymersomes; Liposomes with polymerisable or polymerised bilayer-forming substances
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/51—Nanocapsules; Nanoparticles
- A61K9/5107—Excipients; Inactive ingredients
- A61K9/513—Organic macromolecular compounds; Dendrimers
- A61K9/5146—Organic macromolecular compounds; Dendrimers obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyamines, polyanhydrides
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J13/00—Colloid chemistry, e.g. the production of colloidal materials or their solutions, not otherwise provided for; Making microcapsules or microballoons
- B01J13/02—Making microcapsules or microballoons
- B01J13/06—Making microcapsules or microballoons by phase separation
- B01J13/14—Polymerisation; cross-linking
Abstract
The invention belongs to the field of self-assembled polymer materials and discloses a chemical crosslinked pH value responsive multi-arm polymer and a nano-porous capsule. The polymer comprises a side chain and a main chain; the main chain is a triblock copolymer with a structural formula being block 1-b-block 2-b-block 3, the block 1 is a pH responsive polymer chain, the block 2 is a polymer chain forming a multi-arm bonding structure, and the block 3 is a polymer chain forming a chemical crosslinked structure; the side chain is a hydrophilic polymer side chain and grafted to the block 2. By introduction of the chemical crosslinked chain to the multi-arm polymer, decomposition of encapsulated drugs can be avoided, changing of external temperature is avoided, and simplicity in operation and quantification are realized. By design and regulation of components of each copolymer, crosslinking degree can be controlled.
Description
Technical field
The invention belongs to self assembly polymeric material field, particularly a kind of chemical crosslinking pH value responseMultiarm polymers and nanoporous capsule.
Background technology
Macromolecular self-assembly is to construct to have structure novel substance simple of nanometer or submicron-scale and cleanApproach. Macromolecular self-assembly can build different scale ordered structure, as nano-micelle, and Nano capsule,Nanotube etc. Wherein Nano capsule is the hollow structure of size Nano grade. Because Nano capsule is to haveThe hollow structure of high-specific surface area, can wrap up and protect various active ingredients, as medicine, and organized enzyme, catalysisAgent, dyestuff, sensitiveness material etc., Nano capsule is in new and high technologies such as medicament slow release, catalysis, bioengineeringThere is potential using value in field.
Nano capsule especially has great potentiality in the application in medicine release field. Because present stage is medicalMedicine cannot be avoided the side effect at human body under the condition of carrier-free parcel, and medicine releasing in human bodyPut and cannot be controlled effectively, responsive polymer nano vesicle is as the one of pharmaceutical carrier, for improvingThe transmittability of medicine and target releasability provide a feasible solution.
In recent years, the appearance of a large amount of novel method for synthesizing and technology of preparing, emerges and prepares in a large number Nano capsuleMethod, (such as magnetic, temperature-sensitive, photosensitive, the pH response etc.) intelligence wherein with response is receivedRice vesica is the focus in research. By designing and regulate and control the constituent of multi-arm type polymer, each several part ratioExample and arm prop up chain length, can control the function of vesica.
In existing multiarm polymers synthetic, have by the reaction method of sulfydryl-unsaturated bond and realizeHyperbranched; Or synthetic polymer reacts preparation with coupling agent by the anionic polymerisation of condition harshness.And in the assembling of existing multiarm polymers, common cross-linking method is mainly to utilize ultraviolet light cross-linking structureBuild nano vesicle outer wall, its polymer generally using is polymethylacrylic acid cinnamoyl ethyl ester(PCEMA). Due to the ultraviolet light medicine of can degrading to a certain extent, use PCEMA as grafting altogetherThe crosslinked outer wall of polymers can hinder its utilization discharging at medicine. But not photocrosslinkable polymer system is (such as heatCrosslinked, chemical crosslinking) can avoid the generation of problems.
Summary of the invention
In order to overcome the shortcoming and deficiency of above-mentioned prior art, primary and foremost purpose of the present invention is to provide oneizationLearn crosslinked pH value response multiarm polymers.
Another object of the present invention is to provide a kind of system of above-mentioned chemical crosslinking pH value response multiarm polymersPreparation Method.
Still a further object of the present invention is to provide a kind of Nano capsule, and this Nano capsule is by above-mentioned chemical crosslinkingPH value response multiarm polymers prepares.
A further object of the present invention is to provide the application of above-mentioned Nano capsule.
Object of the present invention realizes by following proposal:
A kind of chemical crosslinking pH value response multiarm polymers, comprises side chain and main chain, wherein,
Described main chain is triblock copolymer, and general structure is: block 1-b-block 2-b-block 3
Wherein, block 1 is pH response macromolecular chain, and block 2 is for forming the high score of multi-arm bonding structureSubchain, block 3 is the macromolecular chain of constitutional chemistry cross-linked structure, side chain is hydrophilic macromolecule side chain, sideChain is grafted on block 2;
The polymer of composition block 1 can be polymethylacrylic acid N, N-dimethylamino ethyl ester(PDMAEMA), polymethylacrylic acid N, N-diethylamino ethyl ester (PDEAEMA) or poly-NIPA (PNIPAM);
The polymer of composition block 2 can be poly (glycidyl methacrylate) (PGMA) or polypropyleneAcid glycidyl ester (PGA);
The polymer of composition block 3 can be poly-N, N-diethylamide ylmethyl ethyl acrylate(PDEAEMA)；
Preferably, in described main chain, the degree of polymerization of the polymer of composition block 1 is 30～60, composition embeddingThe degree of polymerization of the polymer of section 2 is 10～20, and the degree of polymerization of the polymer of composition block 3 is 40～80.
Described side chain is hydrophilic macromolecule chain;
The polymer of composition side chain can be poly glycol monomethyl ether (MPEG) or polyethylene glycol (PEG)In one.
The synthetic of above-mentioned chemical crosslinking pH value response multiarm polymers can be by radical polymerization, controlledThe methods such as radical polymerization or some chemistry are synthetic, and its synthetic method specifically comprises the following steps:
(1) synthetic by pH response macromolecular chain, can multi-arm bonding macromolecular chain and can chemical crosslinking highThe triblock copolymer of strand composition, then can carry out merit by multi-arm bonding macromolecular chain to triblock copolymerEnergyization, obtains trunk polymer;
(2) synthesis hydrophilic polymer is introduced functional group or to after synthetic in building-up process simultaneouslyHydrophilic polymer carries out functionalization, obtains side chain polymer;
(3) main chain copolymer is mixed with side chain polymer, under catalyst exists, carries out single step reaction,Obtain chemical crosslinking pH value response multiarm polymers;
Synthetic triblock copolymer described in step (1) can adopt radical polymerization, controllable free-radicalThe polymerization such as polymerization, anionic polymerisation.
The described functionalization of step (1) refers to can draw on multi-arm bonding macromolecular chain at triblock copolymerEnter nitrine etc.
Synthesis hydrophilic polymer described in step (2) refers to adopt polyethylene glycol or polyethyleneglycol firstEther and 2-propynyl acetic acid carry out esterification and obtain.
The functional group of the introducing described in step (2) and functionalization refer at the end of hydrophilic polymer drawsEnter alkynyl;
The described hydrophilic polymer of step (2) can be MPEG-CCH, PEG-CCH etc.
The described catalyst of step (3) can be CuSO4/ SA (copper sulphate/sodium ascorbate) orCuBr/PMEDTA (cuprous bromide/N, N, N, N, N-five methyl diethylentriamine).
A kind of nanoporous capsule, it is concrete by above-mentioned chemical crosslinking pH value response multiarm polymersStep is as follows: chemical crosslinking pH value response multiarm polymers is dissolved in DMF to past solution after dissolvingIn add the triethylamine aqueous solution of 1mol/L, assemble by solution, then add little molecule crosslinked dose to changeLearn cross-linking reaction, and then add hydrochloric acid to make the pH value of solution to be 4～5, can to form stable nanometerPorous capsule.
Described little molecule crosslinked dose is 1,10-diiodo-decane;
Described chemical crosslink reaction refers to and at room temperature reacts 2h.
Chemical crosslinking pH value response multiarm polymers used, little molecule crosslinked dose, triethylamine aqueous solutionMass ratio be (2～3): 1:90.
Above-mentioned nanoporous capsule can be applied to medicine and discharge, in nano-reactor and nanocatalyst.
The present invention, with respect to prior art, has following advantage and beneficial effect:
(1) traditional photo-crosslinking type polymer need to be cross-linked under ultra violet lamp, and the photograph of uviol lampPenetrate and tend to make the drug moiety that polymer bag carries to decompose, chemical crosslinking type polymer can be avoided this type ofThe generation of situation.
(2) chemical crosslinking is without changing ambient temperature, simple to operate and can quantitatively control crosslinking degree.
(3) the porous nano capsule assembling, effectively Stable Release bag carries bag loading wherein,Play the effect of Stable Release.
Detailed description of the invention
Below in conjunction with embodiment, the present invention is described in further detail, but embodiments of the present invention are not limitIn this.
Umber related in following examples all refers to mass fraction.
In following examples, agents useful for same all can be buied from market routine.
Embodiment 1: a kind of chemical crosslinking pH value response multiarm polymers and nanoporous capsule synthetic
(1) triblock copolymer PDMAEMA-b-PGMA-b-PDEAEMA's is synthetic
Get 1 part of 2-isobutyl ethyl bromide initator, 70 parts of dimethylaminoethyl methacrylates, 100 parts of firstAlcohol, 1 part of CuBr and 1 part of N, " pentamethyl-diethylenetriamine (PMDETA) is at nitrogen for N, N', N', NProtect lower 50 DEG C to carry out ATRP reaction, react and after 6 hours, gained reactant liquor is poured into water, filter,Gained drying precipitate is obtained to PDMAEMA-Br (DP=40);
Get the polymer P DMAEMA-Br of 1 part of above-mentioned acquisition as initator, 20 parts of methacrylic acidsEthylene oxidic ester (GMA), 50 parts of diphenyl ether, 1 part of CuBr and 1 part of N, N, N', N', N " five firstBase diethylenetriamine (PMDETA), under nitrogen protection, normal temperature carries out ATRP reaction, reaction 10After minute, gained reactant liquor is slowly dripped in n-hexane, filter, by gained drying precipitate, obtainPDEAEMA-b-PGMA-Br；
Get again 1 part of PDMAEMA-b-PGMA-Br polymer obtained above, 70 parts of methacrylic acidsDiethylamine ethyl ester, 100 parts of methyl alcohol, 1 part of CuBr and 1 part of N, N, N', N', N " pentamethyl divinyl threeAmine (PMDETA) under nitrogen protection 50 DEG C carry out ATRP reaction, react after 8 hours solutionSlowly splash in n-hexane, dry sediment, obtains triblock copolymerPDMAEMA-b-PGMA-b-PDEAEMA。
(2) PGMA Azide in triblock copolymer PDMAEMA-b-PGMA-b-PDEAEMA
Get 100 parts of triblock copolymer PDMAEMA-b-PGMA-b-PDEAEMA, 50 parts of AzidesSodium, 250 parts of dimethyl formamides (DMF) and a AlCl3, at 50 DEG C, react 24 hours,By the triblock copolymer PDMAEMA-b-PGMA-b-PDEAEMA of Azide.
(3) hydrophilic polymer is synthetic
Get 100 parts of mono methoxy polyethylene glycols (Mn=5000), 20 parts of propinyl acetic acid, 20 parts of 4-bis-Methylamino pyridine (DMAP), 20 parts of 1-(3-dimethylaminopropyl)-3-ethyl carbodiimides hydrochloric acidSalt (EDCHCl) and 200 parts of carrene, 30 DEG C are reacted 24 hours, obtain MPEG-CCH(DP＝114)。
(4) chemical crosslinking pH value response multiarm polymers is synthetic
Get the triblock copolymer PDMAEMA-b-PGMA-b-PDEAEMA, 100 of 10 parts of AzidesPart hydrophilic polymer MPEG-CCH, 250 parts of dimethyl formamides (DMF), then add 1 part of CuSO4And 5 parts of sodium ascorbates, under greenhouse, react 24 hours, can obtain chemical crosslinking pH value response manyArm polymer.
A kind of nanoporous capsule, adopts the method for solution self assembly to obtain, and its preparation method is as follows:
Get 2 parts of above-mentioned chemical crosslinking pH value response multiarm polymers, be dissolved in 10 parts of dimethyl formamides(DMF), in, under stirring, drip gradually the triethylamine aqueous solution of 90 parts of 0.1mol/L. Above-mentioned drippingAfter finishing, greenhouse splashes into 1 part 1 of crosslinking agent under stirring, and 10-diiodo-decane carries out chemical crosslinking 2 hours. After this addEntering hydrochloric acid, to make pH be 4～5, and can obtain nanoporous capsule.
Example 2: a kind of chemical crosslinking pH value response multiarm polymers and nanoporous capsule synthetic
(1) triblock copolymer PDMAEMA-b-PGMA-b-PDEAEMA's is synthetic
Get 1 part of 2-isobutyl ethyl bromide initator, 70 parts of dimethylaminoethyl methacrylates, 100 parts of firstAlcohol, 1 part of CuBr and 1 part of N, " pentamethyl-diethylenetriamine (PMDETA) is at nitrogen for N, N', N', NProtect lower 50 DEG C to carry out ATRP reaction, react and after 6 hours, gained reactant liquor is splashed in water, filter,Gained drying precipitate is obtained to PDMAEMA-Br (DP=40);
Get the polymer P DMAEMA-Br of 1 part of above-mentioned acquisition as initator, 20 parts of methacrylic acidsEthylene oxidic ester (GMA), 50 parts of diphenyl ether, 1 part of CuBr and 1 part of N, N, N', N', N " five firstBase diethylenetriamine (PMDETA), under nitrogen protection, normal temperature carries out ATRP reaction, reaction 10After minute, gained reactant liquor is slowly dripped in n-hexane, filter, gained drying precipitate is obtainedPDMAEMA-b-PGMA-Br；
Get again 1 part of PDMAEMA-b-PGMA-Br polymer obtained above, 70 parts of methacrylic acidsDimethylamine ethyl ester, 100 parts of methyl alcohol, 1 part of CuBr and 1 part of N, N, N', N', N " pentamethyl divinyl threeAmine (PMDETA) under nitrogen protection 50 DEG C carry out ATRP reaction, react after 8 hours gainedReactant liquor, slowly splashes into solution in n-hexane, and dry sediment, obtains triblock copolymerPDEAEMA-b-PGMA-b-PDEAEMA。
(2) PGMA Azide in triblock copolymer PDMAEMA-b-PGMA-b-PDEAEMA
Get 100 parts of triblock copolymer PDMAEMA-b-PGMA-b-PDEAEMA, 50 parts of AzidesSodium, 250 parts of dimethyl formamides (DMF) and a AlCl3, at 50 DEG C, react 24 hours,By the triblock copolymer PDMAEMA-b-PGMA-b-PDEAEMA of Azide.
(3) hydrophilic polymer is synthetic
Get 100 parts of polyethylene glycol (Mn=5000), 20 parts of propinyl acetic acid, 20 parts of 4-dimethylamino pyrrolesPyridine (DMAP), 20 parts of 1-(3-dimethylaminopropyl)-3-ethyl-carbodiimide hydrochloride (EDCHCl) and 200 parts of carrene, 30 DEG C of reactions 24 hours, obtain PEG-CCH (DP=114).
(4) chemical crosslinking pH value response multiarm polymers is synthetic
Get the triblock copolymer PDMAEMA-b-PGMA-b-PDEAEMA, 100 of 10 parts of AzidesPart hydrophilic polymer PEG-CCH, 250 parts of dimethyl formamides (DMF), then add 1 part of CuSO4And 5 parts of sodium ascorbates, under greenhouse, react 24 hours, can obtain chemical crosslinking pH value response manyArm polymer.
A kind of nanoporous capsule, adopts the method for solution self assembly to obtain, and its preparation method is as follows:
Get 2 parts of above-mentioned chemical crosslinking pH value response multiarm polymers, be dissolved in 10 parts of dimethyl formamides(DMF), in, under stirring, drip gradually the triethylamine aqueous solution of 90 parts of 0.1mol/L. Above-mentioned drippingAfter finishing, greenhouse splashes into 1 part 1 of crosslinking agent under stirring, and 10-diiodo-decane carries out chemical crosslinking 2 hours. After this addEntering hydrochloric acid, to make pH be 4～5, and can obtain nanoporous capsule.
Example 3: a kind of chemical crosslinking pH value response multiarm polymers and nanoporous capsule synthetic
(1) triblock copolymer PDEAEMA-b-PGA-b-PDEAEMA's is synthetic
Get 1 part of 2-isobutyl ethyl bromide initator, 70 parts of metering system diethylammonium salt ethyl esters, 100 parts of firstAlcohol, 1 part of CuBr and 1 part of N, " pentamethyl-diethylenetriamine (PMDETA) is at nitrogen for N, N', N', NProtect lower 50 DEG C to carry out ATRP reaction, react 5 hours, afterwards reactant liquor is splashed in water, filter,Gained drying precipitate is obtained to PDEAEMA-Br (DP=40);
Get the polymer P DEAEMA-Br of 1 part of above-mentioned acquisition as initator, 20 parts of acrylic acid shrinkGlyceride (GA), 50 parts of diphenyl ether, 1 part of CuBr and 1 part of N, N, N', N', N " pentamethyl diethylAlkene triamine (PMDETA), under nitrogen protection, normal temperature carries out ATRP reaction, reacts after 10 minutesGained reactant liquor is slowly dripped in n-hexane, filter, gained drying precipitate is obtainedPDEAEMA-b-PGMA-Br；
Get again 1 part of PDEAEMA-b-PGA-Br polymer obtained above, 70 parts of methacrylic acids twoMethylamine ethyl ester, 100 parts of methyl alcohol, 1 part of CuBr and 1 part of N, N, N', N', N " pentamethyl-diethylenetriamine(PMDETA) under nitrogen protection 50 DEG C carry out ATRP reaction, react after 8 hours to obtain three blocksCopolymer p DEAEMA-b-PGA-b-PDEAEMA.
(2) PGMA Azide in triblock copolymer PDEAEMA-b-PGA-b-PDEAEMA
Get 100 parts of triblock copolymer PDEAEMA-b-PGA-b-PDEAEMA, 50 parts of sodium azide,250 parts of dimethyl formamides (DMF) and a AlCl3, at 50 DEG C, react 24 hours, can be by foldedThe triblock copolymer PDEAEMA-b-PGA-b-PDEAEMA of nitrogenize.
(3) hydrophilic polymer is synthetic
Get 100 parts of poly glycol monomethyl ethers (Mn=5000), 20 parts of propinyl acetic acid, 20 parts of 4-diformazansAminopyridine (DMAP), 20 parts of 1-(3-dimethylaminopropyl)-3-ethyl-carbodiimide hydrochloride(EDCHCl) and 200 parts of carrene, 30 DEG C of reactions 24 hours, obtain MPEG-CCH(DP＝114)。
(4) chemical crosslinking pH value response multiarm polymers is synthetic
Get the triblock copolymer PDEAEMA-b-PGA-b-PDEAEMA, 100 parts of 10 parts of AzidesHydrophilic polymer MPEG-CCH, 250 parts of dimethyl formamides (DMF), then add 1 part of CuSO4And 5 parts of sodium ascorbates, under greenhouse, react 24 hours, can obtain chemical crosslinking pH value response manyArm polymer.
A kind of nanoporous capsule, adopts the method for solution self assembly to obtain, and its preparation method is as follows:
Get 2 parts of above-mentioned chemical crosslinking pH value response multiarm polymers, be dissolved in 10 parts of dimethyl formamides(DMF), in, under stirring, drip gradually the triethylamine aqueous solution of 90 parts of 0.1mol/L. Above-mentioned drippingAfter finishing, greenhouse splashes into 1 part 1 of crosslinking agent under stirring, and 10-diiodo-decane carries out chemical crosslinking 2 hours. After this addEntering hydrochloric acid, to make pH be 4～5, and can obtain nanoporous capsule.
Example 4: a kind of chemical crosslinking pH value response multiarm polymers and nanoporous capsule synthetic
(1) triblock copolymer PNIPAM-b-PGMA-b-PDEAEMA's is synthetic
Get 1 part of 2-isobutyl ethyl bromide initator, 80 parts of NIPAs, 100 parts of isopropyl alcohols,1 part of CuBr and 1 part even pyridine (bpy) under nitrogen protection 50 DEG C carry out ATRP reaction, reaction 4After hour, gained reactant liquor is slowly splashed in n-hexane, filter, gained drying precipitate is obtainedPNIPAM-Br；
Get the polymer P NIPAM-Br of 1 part of above-mentioned acquisition as initator, 20 parts of methacrylic acid contractingsWater glyceride (GMA), 50 parts of diphenyl ether, 1 part of CuBr and 1 part of N, N, N', N', N " pentamethylDiethylenetriamine (PMDETA), under nitrogen protection, normal temperature carries out ATRP reaction, reacts 10 pointsAfter clock, gained reactant liquor is slowly dripped in n-hexane, filter, gained drying precipitate is obtainedPDEAEMA-b-PGMA-Br；
Get again 1 part of PNIPAM-b-PGMA-Br polymer obtained above, 70 parts of methacrylic acids twoMethylamine ethyl ester, 100 parts of methyl alcohol, 1 part of CuBr and 1 part of N, N, N', N', N " pentamethyl-diethylenetriamine(PMDETA) under nitrogen protection 50 DEG C carry out ATRP reaction, the reaction time is 8 hours,To triblock copolymer PDEAEMA-b-PGMA-b-PDEAEMA.
(2) PGMA Azide in triblock copolymer PNIPAM-b-PGMA-b-PDEAEMA
Get 100 parts of triblock copolymer PNIPAM-b-PGMA-b-PDEAEMA, 50 parts of sodium azide,250 parts of dimethyl formamides (DMF) and a AlCl3, at 50 DEG C, react 24 hours, can be by foldedThe triblock copolymer PNIPAM-b-PGMA-b-PDEAEMA of nitrogenize.
(3) hydrophilic polymer is synthetic
Get 100 parts of poly glycol monomethyl ethers (Mn=5000), 20 parts of propinyl acetic acid, 20 parts of 4-diformazansAminopyridine (DMAP), 20 parts of 1-(3-dimethylaminopropyl)-3-ethyl-carbodiimide hydrochloride(EDCHCl) and 200 parts of carrene, 30 DEG C of reactions 24 hours, obtain MPEG-CCH(DP＝114)。
(4) chemical crosslinking pH value response multiarm polymers is synthetic
Get the triblock copolymer PNIPAM-b-PGMA-b-PDEAEMA, 100 parts of 10 parts of AzidesHydrophilic polymer MPEG-CCH, 250 parts of dimethyl formamides (DMF), then add 1 part of CuSO4And 5 parts of sodium ascorbates, under greenhouse, react 24 hours, can obtain chemical crosslinking pH value response manyArm polymer.
A kind of nanoporous capsule, adopts the method for solution self assembly to obtain, and its preparation method is as follows:
Get 2 parts of above-mentioned chemical crosslinking pH value response multiarm polymers, be dissolved in 10 parts of dimethyl formamides(DMF), in, under stirring, drip gradually the triethylamine aqueous solution of 90 parts of 0.1mol/L. Above-mentioned drippingAfter finishing, greenhouse splashes into 1 part 1 of crosslinking agent under stirring, and 10-diiodo-decane carries out chemical crosslinking 2 hours. After this addEntering hydrochloric acid, to make pH be 4～5, and can obtain nanoporous capsule.
Embodiment 5: the Stable Release of nanoporous capsule
Preparation method and raw material form all with embodiment 1, and only in step (4), preparation chemical crosslinking pH value is rungIn answering property multiarm polymers Nano capsule, add rhodamine, concrete steps are as follows:
Get chemical crosslinking pH value response multiarm polymers synthetic in 2 parts of above-described embodiments 1,1 part of sieveRed bright, be dissolved in the DMF of 1 part, under 25 DEG C of stirrings, slowly drip the triethylamine water of 9 parts of 0.1mol/LSolution. After 30 minutes, after above-mentioned dropwising, under stirring, greenhouse splashes into 1 part 1,10-diiodo-decane,After chemical crosslinking 2 hours, using the molecular weight that dams is that 14000 dialysis band was by above-mentioned solution dialysis 1 day.Then by the solution freeze drying in dialysis band 2 days, obtain wrapping the Nano capsule that is loaded with rhodamine.
Get 1 part of above-mentioned Nano capsule that is loaded with rhodamine, put into the molecular weight that dams and be 14000 dialysis band,Dialysis band is put into 1mol/L hydrochloric acid, and due under acid condition, nano vesicle becomes nanoporous capsuleBubble, the rhodamine that the inner bag of vesica carries will discharge. Get the distilled water of dialysis band outside, test in ultraviolet(release starts to get once for latter previous hour every 10 minutes, one hour every little half afterwards in observation under instrumentTime get once). Can find the appearance (in 550nm left and right) of the characteristic peak of rhodamine, and dischargeIn 1-30 minute, the amount of release rises gradually, after 30 minutes, discharges gradually steadily and reachesMaximum. After 3 hours, burst size starts slow decreasing. In this process, there is not rhodamineBurst release (if burst release, can there is rising sharply in the content of rhodamine within half an hour, and 3The decline sharply of certain time point in hour) situation, the nanoporous capsule that the present invention is prepared is describedRelease that can be effectively stable bag loading wherein.
Above-described embodiment is preferably embodiment of the present invention, but embodiments of the present invention are not subject to above-mentioned realityExecute routine restriction, other any do not deviate from the change done under Spirit Essence of the present invention and principle, modification,Substitute, combine, simplify, all should be equivalent substitute mode, within being included in protection scope of the present invention.
Claims (9)
1. a chemical crosslinking pH value response multiarm polymers, is characterized in that: comprise side chain and masterChain, described main chain is triblock copolymer, general structure is: block 1-b-block 2-b-block 3, itsMiddle block 1 is pH response macromolecular chain, and block 2 is for forming the macromolecular chain of multi-arm bonding structure, embeddingSection 3 is the macromolecular chain of constitutional chemistry cross-linked structure; Described side chain is hydrophilic macromolecule side chain, side chainBe grafted on block 2;
The polymer of composition block 1 is polymethylacrylic acid N, N-dimethylamino ethyl ester, polymethylAcid N, N-diethylamino ethyl ester or poly-N-isopropyl acrylamide;
The polymer of composition block 2 is poly (glycidyl methacrylate) or polyacrylic acid ethylene oxidic ester;
The polymer of composition block 3 is poly-N, N-diethylamide ylmethyl ethyl acrylate;
The polymer of composition side chain is the one in poly glycol monomethyl ether or polyethylene glycol.
2. a kind of chemical crosslinking pH value response multiarm polymers according to claim 1, its spyLevy and be: the degree of polymerization of the polymer of composition block 1 is 30～60, the polymerization of the polymer of composition block 2Degree is 10～20, and the degree of polymerization of the polymer of composition block 3 is 40～80.
3. a chemical crosslinking pH value response multiarm polymers according to claim 1 and 2Preparation method, is characterized in that comprising the following steps:
(1) synthetic by pH response macromolecular chain, can multi-arm bonding macromolecular chain and can chemical crosslinking highThe triblock copolymer of strand composition, then can carry out merit by multi-arm bonding macromolecular chain to triblock copolymerEnergyization, obtains trunk polymer;
(2) synthesis hydrophilic polymer is introduced functional group or to after synthetic in building-up process simultaneouslyHydrophilic polymer carries out functionalization, obtains side chain polymer;
(3) main chain copolymer is mixed with side chain polymer, under catalyst exists, carries out single step reaction,Obtain chemical crosslinking pH value response multiarm polymers;
Synthetic triblock copolymer described in step (1) adopts radical polymerization, controllable free-radical polymerisationOr anionic polymerisation;
The described synthesis hydrophilic polymer of step (2) refers to adopt polyethylene glycol or poly glycol monomethyl etherCarrying out esterification with 2-propynyl acetic acid obtains;
The described catalyst of step (3) is copper sulphate/sodium ascorbate or cuprous bromide/N, N, N, N, N-fiveMethyl diethylenetriamines.
4. the preparation method of chemical crosslinking pH value response multiarm polymers according to claim 3,It is characterized in that:
The described functionalization of step (1) refers to can draw on multi-arm bonding macromolecular chain at triblock copolymerEnter nitrine;
The functional group of the introducing described in step (2) and functionalization refer at the end of hydrophilic polymer drawsEnter alkynyl.
5. the preparation method of chemical crosslinking pH value response multiarm polymers according to claim 3,It is characterized in that:
The described hydrophilic polymer of step (2) is MPEG-CCH or PEG-CCH.
6. a nanoporous capsule, is characterized in that by the chemical crosslinking pH described in claim 1 or 2Value response multiarm polymers prepares.
7. a preparation method for nanoporous capsule according to claim 6, is characterized in that bagDraw together following steps: chemical crosslinking pH value response multiarm polymers is dissolved in DMF, past molten after dissolvingIn liquid, drip the triethylamine aqueous solution of 1mol/L, assemble by solution, then add little molecule crosslinked dose to carry outChemical crosslinking, and then add hydrochloric acid to make the pH value of solution to be 4～5, to form stabilized nanoscale porous glueCapsule.
8. the preparation method of nanoporous capsule claimed in claim 7, is characterized in that:
Described little molecule crosslinked dose is 1,10-diiodo-decane;
Described chemical crosslinking refers at room temperature cross-linking reaction 2h;
Chemical crosslinking pH value response multiarm polymers used, little molecule crosslinked dose, triethylamine aqueous solutionMass ratio be (2～3): 1:90.
9. nanoporous capsule claimed in claim 6 discharges at medicine, nano-reactor and nano-catalyticApplication in agent.
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| WO2019076911A1 (en) | 2017-10-16 | 2019-04-25 | Calyxia | Method for preparing capsules sensitive to ph or uv radiation and capsules obtained therefrom |
| CN113336879A (en) * | 2021-06-23 | 2021-09-03 | 河北省科学院能源研究所 | Preparation method of pH responsive polymersome with stable structure |
| CN115093515A (en) * | 2022-07-11 | 2022-09-23 | 美服(四川)能源技术有限公司 | Preparation method and application of nano low-friction temperature-sensitive type drag reduction thickener |
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| CN113336879B (en) * | 2021-06-23 | 2022-07-29 | 河北省科学院能源研究所 | Preparation method of pH responsive polymersome with stable structure |
| CN115093515A (en) * | 2022-07-11 | 2022-09-23 | 美服(四川)能源技术有限公司 | Preparation method and application of nano low-friction temperature-sensitive type drag reduction thickener |
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