CN101402738B - Cationic polymer - Google Patents
Cationic polymer Download PDFInfo
- Publication number
- CN101402738B CN101402738B CN2008101445261A CN200810144526A CN101402738B CN 101402738 B CN101402738 B CN 101402738B CN 2008101445261 A CN2008101445261 A CN 2008101445261A CN 200810144526 A CN200810144526 A CN 200810144526A CN 101402738 B CN101402738 B CN 101402738B
- Authority
- CN
- China
- Prior art keywords
- cationic polymers
- alcohol
- hyperbranched
- cationic
- aprotic solvent
- 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.)
- Expired - Fee Related
Links
Images
Landscapes
- Macromolecular Compounds Obtained By Forming Nitrogen-Containing Linkages In General (AREA)
- Addition Polymer Or Copolymer, Post-Treatments, Or Chemical Modifications (AREA)
Abstract
The invention discloses a multipurpose cationic polymer, which is characterized by that a cationic monomer endowing the polymer with composite characteristic and an endosome with destruction characteristic is selected and a small hydrophilic group is introduced so that a cationic polymer with a wide protonation scope, diversified amidogen structure and suitable charge density. The cationic polymer has quite a strong composite capacity over various anionic polyers and metal ions and the capacity for disintegrating the endosome. If being prepared into solution, the cationic polymer can be applied to the development of transgenic products and gene therapy.
Description
Technical field
The present invention relates generally to the synthetic of New Cationic Polymer and in the application of industrial circle and biomedical sector.
Background technology
Cationic polymers is a kind of polyelectrolyte of positively charged, in industrial circle and biomedical sector, has a wide range of applications.In paper industry, cationic polymers can be used as paper strengthening agent, paper waste deinking agent.Aspect building, can be mixed for the road foundation bonding with sand-cement slurry, pitch, fiber etc., increase subgrade strength.In water treatment, cationic polymers can be used as flocculation agent and complexing agent, removes negative electricity organism and toxic heavy metal ion in the waste water, also can make the preparation that Zeo-karb microballoon or film are used for deionized water; The mikrobe that exists in the water in addition can cause equipment corrosion, and particularly in cooling water system, its environment is suitable for the fungus algae microbial growth very much; Make in equipment pipe, to produce settling formation dirt, not only reduced heat transfer efficiency, and caused underdeposit corrosion; Very harmful; In this water system, add the cellularstructure that a certain amount of cationic polymers can destroy microorganisms, stop its metabolism, thereby reach the purpose that sterilization suppresses the microorganism growth breeding; Functions such as cationic polymers has also that foundry loam is peeled off concurrently, flotation, erosion and breakdown of emulsion can be used in the re-injection water treatment in the oil recovery process of oil field.In fabric, add performance and the outward appearance that cationic polymers can improve fabric, be convenient to fabric printing.In coating, cationic polymer emulsion has better water tolerance and mechanical property than anionic polymer emulsion.At biomedical sector, cationic polymers can be used as genophore, and the protection foreign gene is avoided the degraded of nucleicacidase, and promotes gene entering cell to reach in intracellular transfer; Use identical mechanism, cationic polymers also can be used as Anionic Protein and carrier material of macromolecular medicament; Cationic polymers is made microballoon, or cationic polymers is fixed on microsphere surface, can realize enzyme fixing and medicine high flux screening and be about to DNA as a kind of new gene mode of movement and be adsorbed on microsphere surface and carry out transfection then.
In above various application, especially use the highest to the requirement of cationic polymers like genophore with biologic medical.The kind of the molecular weight of cationic polymers, shape of molecule, electric nuclear density, amino and layout, wetting ability etc. all produce significant effects to its application in this respect.Although there is a large amount of cationic polymerss to be synthesized out the research of carrying out the gene transfection aspect, structurally still exists different defects, thereby cause higher toxicity or lower efficient.The efficient gene transfection demands urgently optimizing structure and the cationic polymers of characteristic synthetic in having.
Summary of the invention
Cationic polymer gene vector is one of hope that realizes clinical effective gene treatment, because it is easy to synthetic and modification, non-immunogenicity, be easy to large-scale production, can effectively protect DNA to avoid the degraded of nucleicacidase.Up to now, have a lot of cationic polymer gene vectors to carry out the research of gene transfection aspect, from type say comprise degradable and nondegradable; Polyolefinic, polyester, polymeric amide, poly phosphate, polycarbonate, urethane, polyureas and polyphosphonitrile; Natural, natural modified and synthetic.In this diversified cationic polymers, its core texture unit is the positively charged ion unit aspect gene transfection.Yet what in cationic polymers synthetic, mainly be considered but is not this factor, but some other cofactor.There is deep research in this seminar aspect the optimizing structure of the transfection mechanism of cationic polymer gene vector and cationic polymer gene vector.The cationic monomer of being selected for use among the present invention be exactly testing identity through the synthetic cationic polymers of numerous uses be effective monomer; It has not only given stronger compound ability; And given the ability that endosome is disintegrated, solved interior transfer step of important cell in the gene transfection thus.As the gene transfection carrier, must consider the factor of two aspects: efficient and toxicity with cationic polymers.Efficient is low not to have result of treatment, and toxicity Gao Ze is restricted in clinical use.And also having more deep relation between these two factors, that is exactly the low condition of still not carrying out clinical application of toxicity, and the raising that can help raise efficiency.Because when toxicity is hanged down, there is more viable cell can supply transfection, this just means that having more cell carries out the synthetic of therapeutic coded product.Cationic polymers generally has cytotoxicity, and this toxic source also is its cationic characteristic, and cationic is strong more, and then toxicity is high more.Therefore the toxicity that reduces cationic polymers is an important content in the research cationic polymer gene vector.In the research in this respect, generally admitted two feasible directions, that carries out hydrophilic modifying exactly and introduces the degradable unit.Introduce the degradable unit and in actually operating, be faced with the shortcoming that a degradation rate is difficult to accurate regulation and control, if it is slow to degrade, the toxicity of polymkeric substance can not reduce, if it is too fast to degrade, DNA can not get effective protection.Also be faced with a problem when introducing the hydrophilic modifying group, promptly reduce the protective capability of DNA,, reduced the electric nuclear density of cationic polymers in other words because the introduction of hydrophilic modifying group has shielded the electric charge of cationic polymers.Even after the polymine that electric density is the highest passed through the modification of longer chain polyethylene glycols, transfection efficiency also reduced greatly.The present invention, reduces the toxicity angle from hydrophilic modifying and has synthesized a kind of novel cationic polymers on the basis of cationic monomer preferred.Characteristics of the present invention are; Selected a cationic monomer of giving polymkeric substance composite attribute and endosome destruction characteristic; Introduce a little hydrophilic radical, thereby synthesized a wide protonated scope, the amido structure is various, electric density is suitable cationic polymers.Specifically, this polymkeric substance should have following characteristic: 1) high relatively electric density, so that polymkeric substance has stronger compound ability.Cationic characteristic is cationic polymers embodies its effect in application a basic characteristic; High electric density helps producing between polymkeric substance and the composite object stronger combining; As forming small self-assembly particle with DNA; Help protecting fully DNA, and promote it to reach intracellular transfer in vivo.2) suitable wetting ability strengthens the stability and the biocompatibility of mixture, not serious to the charge generation of polymkeric substance itself again on the other hand shielding effect on the one hand.That is to say, promptly hydrophilic, kept high electric nuclear density again.3) wide protonated scope, so that make mixture have the characteristic of acid response, this specific character is very important as genophore for cationic polymers, because it can avoid DNA to be destroyed by lysosome, promptly so-called proton sponge effect.4) wide amino profile helps enlarging the protonated scope of polymkeric substance.5) material be easy to get, simple synthetic method, be convenient to scale operation and application.
Two of problem to be solved by this invention is to select or synthetic synthetic monomer with cationic polymers of characteristic described in one of problem, i.e. cationic monomer, cross-linking monomer and the end chain hydrophilic modifying monomer of being suitable for.
Three of problem to be solved by this invention be polymkeric substance that research has a characteristic described in one of problem adopt problem two in selected monomeric preparation method.
Four of problem to be solved by this invention be through among model substance research the present invention the compound ability of the cationic polymers that will ask for protection.
Description of drawings
Fig. 1 is the synthesis step and the structure of cationic polymers of the present invention.Various amino in the cationic monomer all have reactive behavior; Therefore in reaction process, have the part primary amine to change secondary amine into, part secondary amine becomes tertiary amine, and the part tertiary amine becomes quaternary ammonium; Therefore institute's synthetic cationic polymers has one-level to level Four amino, and has random hyperbranched form.TBAB among the figure refers to Tetrabutyl amonium bromide.
Fig. 2 is the protonated characteristic of cationic polymers of the present invention.The protonated characteristic of cationic polymers is confirmed with the method for acid base titration; Cationic polymers changes all amidos into the level Four ammonium with hydrochloric acid earlier; Then with the sodium hydroxide solution titration and the variation of measuring the pH value of solution value; Cationic polymers by among visible the present invention among the figure not only can be protonated between pH7.4-11.0, also can be protonated between pH5.0-7.4, explain that the cationic polymers among the present invention not only has the compound ability under the physiological condition; And mixture can demonstrate in sour environment and continue protonatedly, therefore has the proton sponge effect.
Fig. 3 is the particle diameter of the composite particles of cationic polymers of the present invention and model anionic polymer.It is thus clear that the cationic polymers among the present invention has stronger compound ability, can form the composite particles that is no more than 300nm with the model polymkeric substance.The model polymkeric substance of checking compound ability is a ROHM among the present invention.θ among the figure is cationic polymers and the mass ratio of model anionic polymer among the present invention.
Fig. 4 is the stability study of the mixture suspension-s of cationic polymers of the present invention and model anionic polymer.The spectrophotometry that the water stability of research mixture adopts, if because the composite particles instability will be reunited deposition, so the absorbancy of supernatant will reduce.But visible from experimental result, the absorbancy of the suspension-s of the mixture of cationic polymers among the present invention and model anionic polymer did not almost have obvious variation within 7 days, explain that the wetting ability of the cationic polymers among the present invention is better.
Embodiment
The compound method of hydrophilic monomer glycidyl ethyl ether among embodiment one the present invention
Have in reflux condensing tube and induction stirring or the churned mechanically flask 1.10.0mL absolute ethyl alcohol, 27.0mL exsiccant epoxy chloropropane, 0.8g Tetrabutyl amonium bromide join, be warmed up to 40 ℃;
2. divide five times at every turn waiting mass fraction to add 6.9g sodium hydroxide altogether, the interval between each relents with reaction, and the sign that do not seethe with excitement is advisable;
3. after all having added, and when adding afterreaction for the last time and relenting, elevated temperature to 60 ℃ reacts 6h;
4. cooled and filtered reaction mixture, vacuum fractionation.
The compound method of the New Cationic Polymer among embodiment two the present invention
1.20.0mL exsiccant chloroform, 5.00g exsiccant TEPA, 2.45g exsiccant epoxy chloropropane, 1.5g glycidyl ethyl ether join and have in reflux condensing tube and induction stirring or the churned mechanically flask, are warmed up to 60 ℃, reaction 24h;
2. add the 20mL absolute ethyl alcohol, elevated temperature to 90 ℃ is told chloroform;
3. reaction maintains 90 ℃ and carries out 24h;
4. concentrate system is to 10mL, and reaction mixture is poured in the beaker, under intense stirring condition, adds the 20mL ether, and precipitation polymers, polymkeric substance wash three times with ether again, in the process of each washing, and airtight immersion 30min behind the stirring 5min.100 ℃ of dry 24h of vacuum.
Cationic polymers among the present invention has stronger compound ability to various anionic polymers and metals ion in a word; Has the ability of disintegrating endosome; If it wiring solution-forming can be used for transgenic product exploitation and gene therapy; If it is made microballoon or absorption, embedding, immobilized in various microsphere surfaces, then not only can be used for gene transfection, can also be used for heavy metal ion-containing waste water and handle and hydrometallurgy.In addition, if the cationic polymers among the present invention is made the polyelectrolyte composite package, then can be used for multiple uses such as light, electricity, catalysis, medicine controlled releasing.
Claims (6)
1. hyperbranched cationic polymers that has high charge density, wide protonated scope and have excellent hydrophilic; It is characterized in that it is the hyperbranched polymer that is formed at the hydrophilic modifying monomer generation chemical reaction below 500 at the oligopolymer that contains the Edamine structural unit below 580 and epoxy chloropropane linking agent and molecular weight by molecular weight; The glycidyl ether that said hydrophilic modifying monomer is a monohydroxy-alcohol, epoxy monohydroxy-alcohol or epoxy polyol; Wherein monohydroxy-alcohol is straight-chain monohydric alcohol or the branched monobasic alcohol between from methyl alcohol to the decyl alcohol, and polyvalent alcohol is a molecular weight less than the divalent alcohol or the trivalent alcohol of 500 straight or branched.
2. hyperbranched cationic polymers according to claim 1, the mass content that it is characterized in that epoxy chloropropane linking agent structural unit is 0.5-50wt%.
3. hyperbranched cationic polymers according to claim 1 is characterized in that the unitary mass content of hydrophilic modifying monomer structure is 0.5-50wt%.
4. method for preparing like one of claim 1-3 said hyperbranched cationic polymers; It is characterized in that at first various monomers being mixed together in suitable aprotic solvent; Aprotic solvent is methylene dichloride, trichloromethane or tetracol phenixin, at 40-60 ℃ of reaction 10-40h; Steam aprotic solvent, add alcoholic solvent then, elevated temperature is to 80-110 ℃, and reaction continues in this TR, to carry out 24-48h; Or before adding alcoholic solvent, do not steam aprotic solvent, but after adding alcoholic solvent, pass through elevated temperature, the limit coronite is told aprotic solvent; Last concentration of reaction solution adds ether with precipitation polymers under well-stirred condition, polymkeric substance washs three times under agitation condition with ether, and is dry down in 50-100 ℃ of vacuum condition.
5. application form like one of claim 1-3 described hyperbranched cationic polymers; It is characterized in that directly this cationic polymers being made into the aqueous solution uses; Perhaps earlier this cationic polymers is fixed in electroneutral or electronegativity microsphere surface through covalent linkage or ionic linkage, uses the suspension of this positively charged ion microballoon.
6. the application form of a hyperbranched cationic polymers as claimed in claim 5 is characterized in that it is gene transfection, protein drug conveying, enzyme immobilization, heavy metal ion-containing waste water processing, heavy metal ion recovery, the preparation of polyelectrolyte composite package that hyperbranched cationic polymers is specifically used this scope.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2008101445261A CN101402738B (en) | 2007-07-23 | 2008-07-23 | Cationic polymer |
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200710049587 | 2007-07-23 | ||
| CN200710049587.5 | 2007-07-23 | ||
| CN2008101445261A CN101402738B (en) | 2007-07-23 | 2008-07-23 | Cationic polymer |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN101402738A CN101402738A (en) | 2009-04-08 |
| CN101402738B true CN101402738B (en) | 2012-06-06 |
Family
ID=40536914
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2008101445261A Expired - Fee Related CN101402738B (en) | 2007-07-23 | 2008-07-23 | Cationic polymer |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101402738B (en) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102260376B (en) * | 2010-05-24 | 2013-02-27 | 中国科学院上海药物研究所 | Novel cationic polymer used for non-virus type gene carrier, its preparation method and its purpose |
| EP3429651B1 (en) * | 2016-03-17 | 2022-12-21 | TekCyte Limited | Anti-fouling and/or anti-thrombotic medical devices |
| CN110294824B (en) * | 2019-05-31 | 2022-04-22 | 西安理工大学 | Preparation method and application of efficient cationic polymer |
| CN111470576B (en) * | 2020-04-10 | 2022-07-05 | 华东理工大学 | Application of porous cationic polymer in removal of dye or heavy metal in wastewater |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1259152A (en) * | 1997-04-03 | 2000-07-05 | 莱雅公司 | Polymers with thiol terminal function |
| CN1483750A (en) * | 2002-09-20 | 2004-03-24 | 凯 党 | Cation polymer and expansion-resisting agent containing same |
| CN1709924A (en) * | 2005-07-14 | 2005-12-21 | 中国科学院长春应用化学研究所 | Method for preparing water soluble polymer material |
-
2008
- 2008-07-23 CN CN2008101445261A patent/CN101402738B/en not_active Expired - Fee Related
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1259152A (en) * | 1997-04-03 | 2000-07-05 | 莱雅公司 | Polymers with thiol terminal function |
| CN1483750A (en) * | 2002-09-20 | 2004-03-24 | 凯 党 | Cation polymer and expansion-resisting agent containing same |
| CN1709924A (en) * | 2005-07-14 | 2005-12-21 | 中国科学院长春应用化学研究所 | Method for preparing water soluble polymer material |
Also Published As
| Publication number | Publication date |
|---|---|
| CN101402738A (en) | 2009-04-08 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Chen et al. | Synthesis of pH-responsive lignin-based nanocapsules for controlled release of hydrophobic molecules | |
| Mu et al. | Poly (2-vinyl-4, 4-dimethylazlactone)-functionalized magnetic nanoparticles as carriers for enzyme immobilization and its application | |
| Wang et al. | Adsorption of Pb (II) from fish sauce using carboxylated cellulose nanocrystal: Isotherm, kinetics, and thermodynamic studies | |
| Huang et al. | Bifunctional phosphorylcholine-modified adsorbent with enhanced selectivity and antibacterial property for recovering uranium from seawater | |
| CN101402738B (en) | Cationic polymer | |
| Chen et al. | State‐of‐the‐art: applications and industrialization of lignin micro/nano particles | |
| CN109134914B (en) | Preparation method of double-sensitivity cellulose-based aerogel | |
| CN101791408B (en) | Cationic polymer gene vector with low cytotoxicity and high transfection efficiency as well as preparation method and application thereof | |
| Katana et al. | Self-assembly of protamine biomacromolecule on halloysite nanotubes for immobilization of superoxide dismutase enzyme | |
| Fan et al. | Animal-derived natural products review: focus on novel modifications and applications | |
| CN101608020A (en) | Magnetic Fe prepared by hydrothermal method3O4Polymer submicron sphere and application | |
| CN103183832A (en) | Preparation method for magnetic cellulose-chitosan composite microsphere | |
| Kumar et al. | Role of chitosan and chitosan-based nanomaterials in plant sciences | |
| CN105963696B (en) | A kind of preparation method and applications of targeting prussian blue nano particle | |
| Zhu et al. | Preparation and application of lignin nanoparticles: a review | |
| Wang et al. | Development of cationic cellulose-modified bentonite–alginate nanocomposite gels for sustained release of alachlor | |
| Ganguly et al. | Nanocellulose-based polymer nanohybrids and nanocomposite applications | |
| Liu et al. | Magnetic coagulation and flocculation of kaolin suspension using Fe3O4 with plant polyphenol self-assembled flocculants | |
| CN109809545A (en) | A kind of preparation method of efficient dephosphorization coagulant | |
| Lu et al. | Preparation of pH-sensitive lignin nanoparticles and its application in hydrophobic drug delivery | |
| CN103191441A (en) | Method for preparing stimuli-response type esterified nano cellulose prodrug sustained-release material | |
| CN102516536A (en) | Polyethyleneimine (PEI) derivative taking amphipathic chitosan as cross linker and preparation method and application thereof | |
| CN109023951A (en) | A kind of hydrophobic biological matter fiber and preparation method thereof | |
| Pang et al. | Novel surfactant-assisted hydrothermal fabrication of a lignin microsphere as a green reducer and carrier for Pd nanoparticles | |
| Wang et al. | Recent advances in lignin modification and its application in wastewater treatment |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| C17 | Cessation of patent right | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20120606 Termination date: 20130723 |