CN105778015A - Preparation method of amino acid chirality microspheres with water dispersibility and thermosensitivity - Google Patents
Preparation method of amino acid chirality microspheres with water dispersibility and thermosensitivity Download PDFInfo
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- CN105778015A CN105778015A CN201610353365.1A CN201610353365A CN105778015A CN 105778015 A CN105778015 A CN 105778015A CN 201610353365 A CN201610353365 A CN 201610353365A CN 105778015 A CN105778015 A CN 105778015A
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- 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
- C08F283/06—Macromolecular compounds obtained by polymerising monomers on to polymers provided for in subclass C08G on to polyethers, polyoxymethylenes or polyacetals
- C08F283/065—Macromolecular compounds obtained by polymerising monomers on to polymers provided for in subclass C08G on to polyethers, polyoxymethylenes or polyacetals on to unsaturated polyethers, polyoxymethylenes or polyacetals
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Abstract
The invention relates to a preparation method of amino acid chirality microspheres with water dispersibility and thermosensitivity. The method specifically comprises the steps that a thermosensitive amino acid amide chiral monomer M1 and a polyethylene ethanol questin monomer M2 containing a unsaturated bond are adopted as raw materials, and subjected to polymerization with N,N'-methylene bisacrylamide to obtain water dispersibility and thermosensitivity amino acid chirality microspheres, wherein the mass ratio of the M1 to the M2 is 3:1-1:3, and the N,N'-methylene bisacrylamide accounts for 3-5% of the total monomer mass. The microspheres have the potential application value in the aspects of water dispersibility, thermosensitivity, chirality, targeted drug load release and chiral separation.
Description
Technical field
The present invention be more particularly directed to the preparation method of a kind of water dispersible quick acidic amino acid chirality microsphere warm in nature, can be used for medicine
Load with the identification of chipal compounds with separate, particularly belong to high molecular synthetic material technical field.
Background technology
Water dispersible microsphere can be similar to the Core-shell structure material of Micellar properties with stable existence in water, draw in its core
Enter pH value, temperature, illumination, soda acid sensitive polymer, prepare intelligent Core-shell structure material, in targeted drug transport, chirality
Molecular recognition and separation field have potential using value.
The research of the Chiral Micellar Systems that preparation at present has temperature sensitive performance is a lot, but its temperature sensitive performance all derives from additional tool
There is the temperature sensitive performance that the alkyl acryl aminated compounds of Thermo-sensitive rather than chiral polymer itself have, so to target
During the cladding-release or chiral Recognition of medicine, chiral centre all in a kind of inactivity state, passive by
The alkyl acrylamide drive with Thermo-sensitive is coated with and identifies, lacks the motility of chiral centre, impact cladding and knowledge
Other effect.
The present invention uses Thermo-sensitive amino acid amide chiral monomer M1, the PVOH monomethyl ether monomer M2 containing unsaturated bond to be
Raw material, by being polymerized with N, N`-methylene-bisacrylamide, prepares water dispersible quick acidic amino acid microsphere warm in nature.This chirality is gathered
Compound itself has temperature sensitive performance, water dispersible and chirality, and during less than critical solution temperature (LCST), the activeness of himself increases
By force, compare additional Thermo-sensitive compound, be more beneficial for the release of targeted drug；During higher than critical solution temperature (LCST), chirality
Polymer autogenous shrinkage, compares the gel that additional Thermo-sensitive compound is formed, cladding that can be sensitiveer and chiral Recognition performance.
Summary of the invention
It is an object of the invention to provide the preparation method of a kind of water dispersible quick acidic amino acid chirality microsphere warm in nature, for reality
Existing above-mentioned purpose, the preparation method of the present invention is:
Take 100g Thermo-sensitive amino acid amide chiral monomer M1,33.3g～300g PVOH monomethyl ether monomer M2, monomer total
N, the N`-methylene-bisacrylamide of quality 3%～5% is dissolved in the DMF of 500～1500ml, adds the freedom of 0.3～2g
Base initiator, after inflated with nitrogen bubbling 30min, after reacting 8～15h, moves into poly-four under conditions of 70 DEG C～80 DEG C by reactant liquor
In the bag filter of fluorine, dialysing 2 days with water, period every 5h changes a water, then centrifugal treating under conditions of 3000r/min,
Dispersibility Thermo-sensitive amino acid chiral microsphere is obtained after filtrate is freeze-dried；The mass ratio of described monomer M1 and monomer M2 is
3:1～1:3.
Described Thermo-sensitive amino acid amide chiral monomer M1 is modified valine or modified alanine.
Described PVOH monomethyl ether monomer M2 is the one in following 2 kinds of structural formulas:
The number-average molecular weight of described PVOH monomethyl ether monomer M2 is 1000～1900.
Described radical initiator is benzoyl peroxide, the benzoyl peroxide tert-butyl ester, methyl ethyl ketone peroxide, azo
Bis-isobutyronitrile or 2,2'-Azobis(2,4-dimethylvaleronitrile).
The structural formula of described modified valine is the one in following 8 kinds of structural formulas:
The structural formula of described modified alanine is the one in following 4 kinds of structural formulas:
Beneficial effects of the present invention: in the stratum nucleare of water dispersible Thermo-sensitive amino acid chiral microsphere prepared by the present invention rich in
Bisamide bond structure, has strong hydrogen bond action with carrying medicament or chipal compounds, it is simple to load and the identification to medicine, and
Stratum nucleare chiral polymer self has temperature sensitive performance, less than critical solution temperature (LCST) himself activeness strengthen, compare
The additional Thermo-sensitive compound of report, is more beneficial for the release of targeted drug at present；During higher than critical solution temperature (LCST), hands
Property polymer autogenous shrinkage, compare the gel that additional Thermo-sensitive compound is formed, coating medicine that can be sensitiveer.Whole particle
Stable dispersion in aqueous environment, has actual using value in terms of target medicine carrier and chiral Recognition body.
Detailed description of the invention
Illustrate the present invention is further details of below in conjunction with embodiment, but present disclosure is not limited solely to following
Embodiment.
Embodiment 1
Taking 100g Thermo-sensitive amino acid amide chiral monomer L-Val-M1,33.3g molecular weight is the PVOH list first of 1000
Ether monomer M2-1,3.99gN, N`-methylene-bisacrylamide, it is dissolved in 500mL DMF (DMF), adds
Enter the benzoyl peroxide of 0.3g, after filling high pure nitrogen bubbling 30min, be placed in the environment of 80 DEG C heating, after reaction 8h, will be anti-
Answering liquid to move in the bag filter of polytetrafluoro, dialyse 2 days with water, period every 5h changes a water, then in rotating speed be 3000r/min
Under the conditions of centrifugal, remove not dispersed substance, dispersion liquid lyophilization obtains dispersibility Thermo-sensitive aminoacid microsphere.Scanning electron microscope is examined
Surveying particle diameter is 230～650nm, shows temperature sensitive performance at 18～23 DEG C.
Embodiment 2
Taking 100g Thermo-sensitive amino acid amide chiral monomer D-Val-M3,50g molecular weight is the PVOH monomethyl ether of 1000
Monomer M2-1,6gN, N`-methylene-bisacrylamide, it is dissolved in 800mL DMF (DMF), adds 0.6g
Methyl ethyl ketone peroxide, after filling high pure nitrogen bubbling 30min, be placed in the environment of 80 DEG C heating, after reaction 12h, by reactant liquor
Moving in the bag filter of polytetrafluoro, dialyse 2 days with water, period every 5h changes a water, then in rotating speed be 3000r/min condition
Lower centrifugal, remove not dispersed substance, dispersion liquid lyophilization obtains dispersibility Thermo-sensitive aminoacid microsphere.Scanning electron microscope detection grain
Footpath is 280～750nm, shows temperature sensitive performance at 16～20 DEG C.
Embodiment 3
Taking 100g Thermo-sensitive amino acid amide chiral monomer D-Ala-M1,150g molecular weight is the PVOH monomethyl ether of 1900
Monomer M2-2,8gN, N`-methylene-bisacrylamide, it is dissolved in 1000mL DMF (DMF), adds
The azodiisobutyronitrile of 0.8g, after filling high pure nitrogen bubbling 30min, is placed in the environment of 70 DEG C heating, after reaction 15h, and will be anti-
Answering liquid to move in the bag filter of polytetrafluoro, dialyse 2 days with water, period every 5h changes a water, then in rotating speed be 3000r/min
Under the conditions of centrifugal, remove not dispersed substance, dispersion liquid lyophilization obtains dispersibility Thermo-sensitive aminoacid microsphere.Scanning electron microscope is examined
Surveying particle diameter is 330～760nm, shows temperature sensitive performance at 8～12 DEG C.
Embodiment 4
Taking 100g Thermo-sensitive amino acid amide chiral monomer D-Ala-M2,300g molecular weight is the PVOH monomethyl ether of 1900
Monomer M2-2,12g N, N`-methylene-bisacrylamide, is dissolved in 1500mL DMF (DMF), adds
The azodiisobutyronitrile of 1.8g, after filling high pure nitrogen bubbling 30min, is placed in the environment of 70 DEG C heating, after reaction 12h, and will be anti-
Answering liquid to move in the bag filter of polytetrafluoro, dialyse 2 days with water, period every 5h changes a water, then in rotating speed be 3000r/min
Under the conditions of centrifugal, remove not dispersed substance, dispersion liquid lyophilization obtains dispersibility Thermo-sensitive aminoacid microsphere.Scanning electron microscope is examined
Surveying particle diameter is 510～960nm, shows temperature sensitive performance at 7～12 DEG C.
Claims (7)
1. the preparation method of a water dispersible quick acidic amino acid chirality microsphere warm in nature, it is characterised in that: described preparation method:
Take 100g Thermo-sensitive amino acid amide chiral monomer M1,33.3g～300g PVOH monomethyl ether monomer M2, monomer gross mass 3%
～the N of 5%, N`-methylene-bisacrylamide is dissolved in the DMF of 500～1500ml, and the free radical adding 0.3～2g causes
Agent, after inflated with nitrogen bubbling 30min, after reacting 8～15h, moves into the saturating of polytetrafluoro under conditions of 70 DEG C～80 DEG C by reactant liquor
In analysis bag, dialysing 2 days with water, period every 5h changes a water, then centrifugal treating under conditions of 3000r/min, filtrate warp
Dispersibility Thermo-sensitive amino acid chiral microsphere is obtained after lyophilization；The mass ratio of described monomer M1 and monomer M2 be 3:1～
1:3。
The preparation method of a kind of water dispersible quick acidic amino acid chirality microsphere warm in nature the most according to claim 1, its feature
Being, described Thermo-sensitive amino acid amide chiral monomer M1 is modified valine or modified alanine.
The preparation method of a kind of water dispersible quick acidic amino acid chirality microsphere warm in nature the most according to claim 1, its feature
It is: described PVOH monomethyl ether monomer M2 is the one in following 2 kinds of structural formulas:
。
The preparation method of a kind of water dispersible quick acidic amino acid chirality microsphere warm in nature the most according to claim 1, its feature
It is: the number-average molecular weight of described PVOH monomethyl ether monomer M2 is 1000～1900.
The preparation method of a kind of water dispersible quick acidic amino acid chirality microsphere warm in nature the most according to claim 1, its feature
It is: described radical initiator is benzoyl peroxide, the benzoyl peroxide tert-butyl ester, methyl ethyl ketone peroxide, azo two
Isopropyl cyanide or 2,2'-Azobis(2,4-dimethylvaleronitrile).
Modified valine the most according to claim 2, it is characterised in that: the structural formula of described modified valine is following
One in 8 kinds of structural formulas:
。
Modified alanine the most according to claim 2, it is characterised in that: the structural formula of described modified alanine is following
One in 4 kinds of structural formulas:
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107501451A (en) * | 2017-09-01 | 2017-12-22 | 北方民族大学 | Chiral CO2Respond ethyleneamino acid polymer and preparation method thereof |
Citations (4)
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|---|---|---|---|---|
| CN101130606A (en) * | 2007-08-03 | 2008-02-27 | 中国科学院广州化学研究所 | Water dispersible magnetic polymer microsphere, preparing method and application of the same |
| CN102432746A (en) * | 2011-09-26 | 2012-05-02 | 天津工业大学 | Temperature-responsive L-amino-acid-modified chiral high-molecular hydrogel |
| CN102659981A (en) * | 2012-05-21 | 2012-09-12 | 天津工业大学 | Temperature sensitive type microgel modified by L-amino acid |
| CN102659974A (en) * | 2012-05-21 | 2012-09-12 | 天津工业大学 | pH response type gel modified by L-amino acid |
-
2016
- 2016-05-25 CN CN201610353365.1A patent/CN105778015A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101130606A (en) * | 2007-08-03 | 2008-02-27 | 中国科学院广州化学研究所 | Water dispersible magnetic polymer microsphere, preparing method and application of the same |
| CN102432746A (en) * | 2011-09-26 | 2012-05-02 | 天津工业大学 | Temperature-responsive L-amino-acid-modified chiral high-molecular hydrogel |
| CN102659981A (en) * | 2012-05-21 | 2012-09-12 | 天津工业大学 | Temperature sensitive type microgel modified by L-amino acid |
| CN102659974A (en) * | 2012-05-21 | 2012-09-12 | 天津工业大学 | pH response type gel modified by L-amino acid |
Non-Patent Citations (3)
| Title |
|---|
| AKIRA DOBASHI等: "Control of the Solubility Transition in Novel Temperature-Responsive Linear Polymers Comprising α-Amino Acid Diamide Derivatives", 《ANALYTICAL SCIENCES》 * |
| ZHILEI LIU等: "Preparation of Thermoresponsive Polymers Bearing Amino Acid Diamide Derivatives via RAFT Polymerization", 《JOURNAL OF POLYMER SCIENCE: PART A: POLYMER CHEMISTRY》 * |
| 陈娇娇等: "手性温敏凝胶P(NIPAM-co-NALL)的制备及识别性能", 《高等学校化学学报》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107501451A (en) * | 2017-09-01 | 2017-12-22 | 北方民族大学 | Chiral CO2Respond ethyleneamino acid polymer and preparation method thereof |
| CN107501451B (en) * | 2017-09-01 | 2019-07-02 | 北方民族大学 | Chiral CO2Respond ethyleneamino acid polymer and preparation method thereof |
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