CN106008807A - Preparation method of amino acid chiral gel with stepped temperature sensitivity - Google Patents
Preparation method of amino acid chiral gel with stepped temperature sensitivity Download PDFInfo
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- CN106008807A CN106008807A CN201610351911.8A CN201610351911A CN106008807A CN 106008807 A CN106008807 A CN 106008807A CN 201610351911 A CN201610351911 A CN 201610351911A CN 106008807 A CN106008807 A CN 106008807A
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- amino acid
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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
- C08F220/00—Copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and only one being terminated by only one carboxyl radical or a salt, anhydride ester, amide, imide or nitrile thereof
- C08F220/02—Monocarboxylic acids having less than ten carbon atoms; Derivatives thereof
- C08F220/52—Amides or imides
- C08F220/54—Amides, e.g. N,N-dimethylacrylamide or N-isopropylacrylamide
- C08F220/60—Amides, e.g. N,N-dimethylacrylamide or N-isopropylacrylamide containing nitrogen in addition to the carbonamido nitrogen
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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
- C08F220/00—Copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and only one being terminated by only one carboxyl radical or a salt, anhydride ester, amide, imide or nitrile thereof
- C08F220/02—Monocarboxylic acids having less than ten carbon atoms; Derivatives thereof
- C08F220/52—Amides or imides
- C08F220/54—Amides, e.g. N,N-dimethylacrylamide or N-isopropylacrylamide
- C08F220/60—Amides, e.g. N,N-dimethylacrylamide or N-isopropylacrylamide containing nitrogen in addition to the carbonamido nitrogen
- C08F220/603—Amides, e.g. N,N-dimethylacrylamide or N-isopropylacrylamide containing nitrogen in addition to the carbonamido nitrogen and containing oxygen in addition to the carbonamido oxygen and nitrogen
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- Chemical Kinetics & Catalysis (AREA)
- Medicinal Chemistry (AREA)
- Polymers & Plastics (AREA)
- Organic Chemistry (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
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Abstract
The invention discloses a preparation method of amino acid chiral gel with stepped temperature sensitivity. The amino acid chiral gel with stepped temperature sensitivity is prepared by adopting a temperature-sensitive amino acid amide chiral monomer M1, a achiral alkyl acrylamide monomer M2 with temperature sensitivity and a chemical crosslinking agent N,N'-methylene bisacrylamide as raw materials through radical-initiated polymerization, wherein the amino acid amide chiral monomer M1 is modified valine or modified alanine; the alkyl acrylamide monomer M2 is N,N-diethyl acrylamide or N-isopropyl acrylamide; a radical initiator is benzoyl peroxide, tert-butyl benzoyl peroxide, methyl ethyl ketone peroxide, azodiisobutyronitrile or azobisisoheptonitrile; the mass ratio of M1 to M2 is (3:1)-(1:3); and the N,N'-methylene bisacrylamide accounts for 5-10% of the total mass of the monomer. The amino acid chiral gel has obvious stepped temperature sensitivity and chirality and has potential application value in terms of drug encapsulation-release and chiral separation.
Description
Technical field
A kind of preparation method with ladder temperature sensitive acidic amino acid chiral gel of the present invention, can be used for the identification of drug loading and chipal compounds and divides
From, particularly belong to high molecular synthetic material technical field.
Background technology
High-molecular gel be by macromolecular chain between chemical bond or physical force formed three-dimensional crosslinking structure, in its structure introduce pH value,
Temperature, illumination, soda acid sensitive polymer, will make whole gel stimulate generation response to external world, thus prepare intelligent hydrogels, give birth to
The fields such as thing medical science, organizational project, control device have a wide range of applications.And in high-molecular gel, introduce chiral radicals, then at drug loading and
Identification and the separation aspect of chiral compound have potential using value.
Responsive to temperature type chiral gel is combined with the pluralgel of temperature sensitive performance and chirality function, utilizes chiral radicals coating medicine or chiral compound
Thing, utilizes temperature sensitive performance to discharge the medicine being coated with, owing to different pharmaceutical is different from the active force of chiral radicals, thus produces different rates of release,
Reach the effect of slow release and separation.A kind of chiral gel slow release for tumour medicine it is prepared in patent CN102525882A；In patent
CN102659981A, CN104031261A, CN201210157406.1 and CN201110287856.8 are prepared for respectively a kind of containing amino
The thermo-responsive hydro gel of acid, its temperature sensitive performance derives from the additional alkyl acrylamide with Thermo-sensitive rather than chiral center self has Thermo-sensitive
Can, so during cladding-release medicine or chiral Recognition, chiral centre is all in a kind of inactivity state, and passive is temperature sensitive by having
Property alkyl acrylamide drive be coated with and identify, lack chiral centre motility, impact cladding and identify effect.
The present invention uses Thermo-sensitive amino acid amide chiral monomer M1, the achirality alkyl propionic acid amide. monomer M2 with Thermo-sensitive, chemical crosslinking monomer
N, N`-methylene-bisacrylamide is raw material, and being had by free radical polymerization preparation has ladder temperature sensitive acidic amino acid chiral gel, and this gel exists
Two lower critical solution temperatures (LCST) can be formed between 30～34 DEG C and at being less than 25 DEG C, different from medicine active force according to polymer, Ke Yixuan
Selecting property absorption medicine, and realize the release of the staged to medicine by controlling temperature, at medicament slow release and chiral separation field, there is potential application valency
Value.
Summary of the invention:
It is an object of the invention to provide a kind of preparation method with ladder temperature sensitive acidic amino acid chiral gel.To achieve these goals, system of the present invention
Preparation Method particularly as follows:
Take the achirality alkyl acryl amine monomers M2 of 100g Thermo-sensitive amino acid amide chiral monomer M1,33.3g～300g Thermo-sensitive, monomer total
The 5% of quality～the N of 10%, N`-methylene-bisacrylamide be dissolved in the DMF of 500～1400ml, add 0.3～2g radical initiator,
After inflated with nitrogen bubbling 30min, under conditions of 70 DEG C～80 DEG C, react 8～15h；Thereafter, respectively through changing DMF immersion product in 15h
After 3 times, then changing soak with ethanol product in 15h respectively 3 times, the product after immersion treatment is vacuum dried after filtering, obtains ammonia
Base acid chiral gel；The mass ratio of described Thermo-sensitive amino acid monomer M1 and the achirality alkyl acryl amine monomers M2 of Thermo-sensitive controls
3:1～1:3.
Described Thermo-sensitive amino acid amide chiral monomer M1 is modified valine or alanine.
The achirality alkyl acryl amine monomers M2 of described Thermo-sensitive is N, N-acrylamide or NIPA.
Described radical initiator is benzoyl peroxide, the benzoyl peroxide tert-butyl ester, methyl ethyl ketone peroxide, azodiisobutyronitrile or azo two
Different heptonitrile.
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:
The Thermo-sensitive amino acid amide chiral monomer M1 that the present invention uses contains bisamide bond structure, has strong hydrogen with carrying medicament or chipal compounds
Key effect, it is simple to load and the identification to medicine, then chiral monomer M1 again with have Thermo-sensitive achirality alkyl acryl amine monomers M2,
Cross-linking agent passes through copolymerization, prepares the chiral gel with ladder Thermo-sensitive.The chiral center of this chiral gel self has temperature sensitive performance, can select
Property absorption medicine, and realize the staged of medicine is discharged by controlling temperature, there is Thermo-sensitive and chiral Recognition performance, can be the sensitiveest controlled
Ground cladding, release, chiral Recognition medicine.
Detailed description of the invention
Illustrate the present invention is further details of below in conjunction with embodiment, but present invention is not limited solely to example below.
Embodiment 1
Take 100g Thermo-sensitive amino acid amide monomer D-Val-M1,33.3g N, N-acrylamide and 6.65g N, N`-methylene bisacrylamide acyl
Amine, is dissolved in 500mL DMF (DMF), adds the benzoyl peroxide of 0.3g, fills high pure nitrogen bubbling 30min
After, it is placed in the environment of 80 DEG C heating, after reaction 8h, first soaks 5h with DMF, after changing 3 times, use soak with ethanol 2h, after changing 3 times,
Vacuum drying.The temperature sensitive performance of ladder occurs between 18～22 DEG C and 30～34 DEG C.
Embodiment 2
Take 100g Thermo-sensitive amino acid amide monomer L-Val-M4,150g N, N-acrylamide and 15g N, N`-methylene-bisacrylamide,
It is dissolved in 110mL DMF (DMF), adds the benzoyl peroxide tert-butyl ester of 1.4g, fill high pure nitrogen bubbling 30min
After, it is placed in the environment of 80 DEG C heating, after reaction 12h, first soaks 5h with DMF, after changing 3 times, use soak with ethanol 2h, after changing 3 times,
Vacuum drying.The temperature sensitive performance of ladder occurs between 18～22 DEG C and 30～33 DEG C.
Embodiment 3
Take 100g Thermo-sensitive amino acid amide monomer L-Ala-M2,300g N, N-acrylamide and 30g N, N`-methylene-bisacrylamide,
It is dissolved in 1400mL DMF (DMF), adds the azodiisobutyronitrile of 2g, after filling high pure nitrogen bubbling 30min, put
Heat in the environment of 70 DEG C, after reaction 15h, first soak 5h with DMF, after changing 3 times, use soak with ethanol 2h, after changing 3 times, vacuum
It is dried.The temperature sensitive performance of ladder occurs between 8～12 DEG C and 30～33 DEG C.
Embodiment 4
Take 100g Thermo-sensitive amino acid amide monomer D-Ala-M1,200g N, N-acrylamide and 20g N, N`-methylene-bisacrylamide,
It is dissolved in 1300mL DMF (DMF), adds the azodiisobutyronitrile of 1.4g, after filling high pure nitrogen bubbling 30min,
It is placed in the environment of 70 DEG C heating, after reaction 15h, first soaks 5h with DMF, after changing 3 times, use soak with ethanol 2h, after changing 3 times,
Vacuum drying.The temperature sensitive performance of ladder occurs between 8～13 DEG C and 30～34 DEG C.
Claims (6)
1. a preparation method with ladder temperature sensitive acidic amino acid chiral gel, it is characterised in that: described preparation method is: take 100g Thermo-sensitive
Achirality alkyl acryl amine monomers M2, the 5% of monomer gross mass～10% of amino acid amide chiral monomer M1,33.3g～300g Thermo-sensitive
N, N`-methylene-bisacrylamide is dissolved in the DMF of 500～1400ml, adds the radical initiator of 0.3～2g, inflated with nitrogen bubbling 30min
After, under conditions of 70 DEG C～80 DEG C, react 8～15h；Thereafter, in 15h respectively after changing DMF and soaking product 3 times, then at 15h
Changing soak with ethanol product 3 times the most respectively, the product after immersion treatment is vacuum dried after filtering, obtains amino acid chiral gel；Institute
The mass ratio of the Thermo-sensitive amino acid monomer M1 stated and the achirality alkyl acryl amine monomers M2 of Thermo-sensitive controls as 3:1～1:3.
A kind of preparation method with ladder temperature sensitive acidic amino acid chiral gel the most according to claim 1, it is characterised in that: described temperature
Quick acidic amino acid amide chiral monomer M1 is modified valine or modified alanine.
A kind of preparation method with ladder temperature sensitive acidic amino acid chiral gel the most according to claim 1, it is characterised in that: described temperature
The achirality alkyl acryl amine monomers M2 of quick property is N, N-acrylamide or NIPA.
A kind of preparation method with ladder temperature sensitive acidic amino acid chiral gel the most according to claim 1, it is characterised in that: described from
It is benzoyl peroxide, the benzoyl peroxide tert-butyl ester, methyl ethyl ketone peroxide by base initiator, azodiisobutyronitrile 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 8 kinds of structural formulas
In one:
Modified alanine the most according to claim 2, it is characterised in that: the structural formula of described modified alanine is following 4 kinds of structural formulas
In one:
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
-
2016
- 2016-05-25 CN CN201610351911.8A patent/CN106008807A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
Non-Patent Citations (3)
| Title |
|---|
| CHEN JIAOJIAO等: "Preparation and Recognization Property of Chiral Thermo-sensitive P(NIPAM-co-NALL) Hydrogels", 《CHEMICAL JOURNAL OF CHINESE UNIVERSITIES-CHINESE》 * |
| DOBASHI, AKIRA等: "Control of the solubility transition in novel temperature-responsive linear polymers comprising α-amino acid diamide derivatives", 《ANALYTICAL SCIENCES》 * |
| LIU, ZHILEI等: "Preparation of thermoresponsive polymers bearing amino acid diamide derivatives via RAFT polymerization", 《JOURNAL OF POLYMER SCIENCE, PART A: POLYMER CHEMISTRY》 * |
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Application publication date: 20161012 |