JP2007070579A - Star type polymer, method for synthesizing the same and vector - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a method for synthesizing a star type polymer which can be used for synthesizing the star type polymer with a good efficiency through performing a light irradiation living polymerization by the use of a compound having four or more N, N-dialkyl-dithiocarbamyl methyl groups in the same molecule as an iniferter, and to provide a vector comprising the star type polymer produced by the method. <P>SOLUTION: The method for synthesizing the star type polymer through performing a light irradiation living polymerization by the use of a compound having four or more N, N-dialkyl-dithiocarbamyl methyl groups in the same molecule as an iniferter comprises a process of preparing a raw material solution by dissolving a monomer and the iniferter in a nonpolar solvent, a first light irradiation process for irradiating a light to the raw material solution, a dilution process for diluting the irradiated solution with an alcohol, and a second light irradiation process for irradiating light into the diluted solution. The vector is prepared by the method. <P>COPYRIGHT: (C)2007,JPO&INPIT

Description

  The present invention relates to a method for synthesizing a star polymer, a star polymer synthesized by this method, and a vector comprising the star polymer.

  Dioleoyloxypropyltrimethylammonium (Felgner et al., Proc), a cationic lipid commercialized as Lipofectin® as a non-viral vector for delivering DNA into cells. Natl. Acad. Sci. USA, 84, 7413-7417, 1987). Polyethyleneimine is also commercialized as Exogen as a vector polymer.

  Nucleic acids are generally not very stable in vivo and are degraded by certain enzymes. The present applicant has disclosed a vector composed of a cationic polymer having a branched chain as a vector capable of protecting a nucleic acid from an aggregate and arranging a vector containing a cationic polymer around the aggregate to protect it from an enzyme. It is proposed in 092388 A1.

  This vector forms a complex with a nucleic acid aggregate and is administered into a living body.

  In this publication, as a specific example of this vector, a vector comprising a compound in which 2 to 6 branched chains are radially branched from the benzene ring of a benzene derivative is described.

  Specifically, the same publication discloses the following as a benzene derivative serving as a nucleus to which a branched chain is bonded. That is, for the three-branched chain, 2,4,6-tris (N, N) obtained by addition reaction of 2,4,6-tris (bromomethyl) mesitylene and sodium N, N-diethyldithiocarbamate in ethanol. N-diethyldithiocarbamylmethyl) mesitylene, obtained as an addition reaction of 1,2,4,5-tetrakis (bromomethyl) benzene and sodium N, N-diethyldithiocarbamate in ethanol. 1,2,4,5-tetrakis (N, N-diethyldithiocarbamylmethyl) benzene, and six-branched chains are hexakis (bromomethyl) benzene and sodium N, N-diethyldithiocarbamate in ethanol. Hexakis (N, N-diethyldithiocarbamylmethyl) benzone obtained by addition reaction It is down.

As a preferred example of this branched chain, a polymer of 3-N, N-dimethylaminopropylacrylamide CH ₂ ═CHCONHC ₃ H ₆ N (CH ₃ ) ₂ is mentioned.

This 3-N, N-dimethylaminopropylacrylamide and each of the above benzene derivatives serving as nuclei are mixed as an alcohol solution such as methanol or as a nonpolar solvent solution such as chloroform in consideration of solubility, and photopolymerization reaction is performed. By doing so, a polymer of the vinyl monomer is bonded to the benzene ring via —CH ₂ — derived from the benzene derivative, and a cationic polymer is formed in which a branched chain is formed radially. The vector made of the cationic polymer thus produced has a high charge density, and as a result, the nucleic acid-containing complex formed from the cationic polymer and the nucleic acid is also a high-density one. Because of the three-dimensional structure that is not easily affected by the action of nucleic acids, it is possible to suppress inactivation and degradation of nucleic acids.

  In this publication, naphthalene, anthracene and pyrene are also described as other than benzene derivatives.

  The above synthesis reaction is a light irradiation living polymerization reaction using the benzene derivative or the like as an iniferter.

  In this specification, the iniferter is a polymerization initiator that generates radicals upon irradiation with light, a function as a chain transfer agent, a function that bonds with the growth terminal to stop the growth, and a polymerization when light irradiation stops. It is a molecule that functions as a polymerization initiator / termination agent for stopping.

Among the iniferters composed of the above benzene derivatives and the like described in WO2004 / 092388 A1, those having four or more branched chains are hardly soluble in alcohol. This iniferter is soluble in benzene and toluene. It is also soluble in alkyl halides such as chloroform and methylene chloride.
WO2004 / 092388 A1

(1) The light absorption wavelength of dithiocarbamate is in the range of about 240 nm to 300 nm, and it is possible to carry out polymerization by radical cleavage efficiently by irradiating light of this wavelength. Since benzene and toluene, which are good solvents for iniferters, have light absorption derived from aromatic rings in the vicinity of 250 nm to 260 nm, the solvent itself absorbs light of a wavelength that efficiently radically cleaves the iniferter. It will antagonize light absorption.

  At the laboratory level where the optical path is short, i.e., polymerization is carried out with a small volume, even if the solvent absorbs light, the light reaches the entire region of the container. When the optical path becomes long in a large-capacity reaction vessel such as mass production, polymerization proceeds only on the surface of the vessel on the light incident side due to light absorption by the solvent. On the surface of the container on the light incident side, cross-linking between molecules and decomposition of the polymer occur in a complicated manner, so that a polymer having a large molecular weight as the target product cannot be obtained efficiently.

(2) The above-mentioned good solvents such as chloroform and methylene chloride do not absorb light in the range of 240 to 300 nm, and light irradiation polymerization using them has a long optical path, that is, even in a large-scale reaction vessel with a large production scale. Polymerization is possible.

  However, chloroform or the like easily causes chain transfer from the polymer growth chain, and contributes to the growth termination reaction of the target iniferter polymer. In addition, polymerization occurs using radicals generated by photolysis of chloroform or the like as initiators, and homopolymers unrelated to the iniferter are generated. Furthermore, since the halogenated alkyl radical contributing to the growth termination reaction deactivates the living terminal, it becomes impossible to increase the degree of polymerization and to synthesize the AB type block polymer.

  The AB type block polymer is a block polymer synthesized by polymerizing the A monomer, isolating the polymer, and then performing light irradiation in a system with the B monomer.

  The present invention solves the above problems and efficiently synthesizes a star polymer by light irradiation living polymerization using an iniferter as a compound having four or more N, N-dialkyl-dithiocarbamylmethyl molecular groups in the same molecule. It is an object to provide a method for synthesizing a star polymer.

  The method for synthesizing a star polymer according to claim 1 comprises synthesizing a star polymer by light irradiation living polymerization using a compound having four or more N, N-dialkyl-dithiocarbamylmethyl molecular groups in the same molecule as an iniferter. A method of preparing a raw material solution in which a monomer and an iniferter are dissolved in a non-polar solvent; a first light irradiation step of irradiating light into the raw material solution; and It has a dilution process for diluting and a second light irradiation process for irradiating the diluted solution with light.

  The method for synthesizing a star polymer according to claim 2 is the method according to claim 1, wherein the compound having four or more N, N-dialkyl-dithiocarbamylmethyl groups in the same molecule is a benzene ring, a naphthalene ring or an anthracene ring. , Biphenyl ring, biphenylene ring, pyridine ring, pyrrole ring, furan ring or pyrene ring as a nucleus, and four or more N, N-dialkyl-dithiocarbamylmethyl molecular groups are bonded to this nucleus as a branched chain. It is characterized by this.

  A method for synthesizing a star polymer according to claim 3 is characterized in that, in claim 1 or 2, the monomer is a vinyl monomer.

  The method for synthesizing a star polymer according to claim 4 is characterized in that, in claim 3, the vinyl monomer is 3-N, N-dimethylaminopropylacrylamide.

  The method for synthesizing a star polymer according to claim 5 is characterized in that, in claim 4, the solvent is an alkyl halide or an alkylene halide.

  The method for synthesizing a star polymer according to claim 6 is characterized in that, in claim 4, the solvent is chloroform, carbon tetrachloride or methylene chloride.

  The method for synthesizing a star polymer according to claim 7 is characterized in that, in claim 4, the solvent is chloroform.

  The method for synthesizing a star polymer according to claim 8 is characterized in that, in any one of claims 1 to 7, the monomer concentration in the raw material solution is 70% by weight or more.

  The method for synthesizing a star polymer according to claim 9 is characterized in that, in any one of claims 1 to 8, the wavelength of light in the first light irradiation step is 240 to 300 nm.

  The method for synthesizing a star polymer according to claim 10 is characterized in that, in any one of claims 1 to 9, the alcohol is methanol.

  The method for synthesizing a star polymer according to claim 11 is characterized in that, in any one of claims 1 to 10, the alcohol is an alcohol solution of the monomer.

  The star polymer according to claim 12 is synthesized by the method according to any one of claims 1 to 11.

  The star polymer of claim 13 is obtained by additionally polymerizing the star polymer of claim 12 with a vinyl monomer different from the monomer used for the star polymer monomer.

  The vector according to claim 14 comprises the star polymer according to claim 12 or 13.

  According to the method for synthesizing the star polymer of the present invention, the light irradiation living polymerization reaction is performed in a nonpolar solvent only in the initial stage of the light irradiation living polymerization, and then the light irradiation living polymerization is performed in an alcohol solvent. Thereby, a star polymer can be efficiently synthesized by light irradiation living polymerization using a compound having four or more N, N-dialkyl-dithiocarbamylmethyl molecular groups in the same molecule as an iniferter.

The main points of the present invention are as follows.
(1) Does not absorb in the range of 240 nm to 300 nm, which is the light absorption wavelength of dithiocarbamate, and does not easily cause radical chain transfer unlike alkyl halides, and easily decomposes to generate radicals. Polymerization is carried out using alcohol as a solvent.
(2) However, alcohol is a poor solvent that does not dissolve iniferters. If an iniferter is dissolved in chloroform or benzene and then dropped into alcohol, the iniferter immediately precipitates.
(3) A flowable high-viscosity solution is obtained by mixing a paste in which iniferter is dissolved in a small amount of chloroform or toluene with a monomer. The monomer content in the high-viscosity solution is about 90%. Performing polymerization in this state makes it impossible to donate the monomer homogeneously to the chain reaction due to the risk of runaway reaction, high viscosity, and poor diffusibility.
(4) When the paste is put into a small container with a short optical path and irradiated with monochromatic light having a low energy, preferably 240 to 300 nm, the dithiocarbamate molecular group is cleaved to generate radicals and undergo monomer addition. If the polymerization is continued as it is, a bulk polymer with a heterogeneous molecular weight distribution and many intermolecular crosslinks is formed. In the present invention, the irradiation time of the monochromatic light is shortened, and the irradiation is stopped when several molecules of monomer are added to the iniferter. In this state, the iniferter is apparently soluble in alcohol (although in a short time). Therefore, homogeneous polymerization can be performed by irradiating light as a low viscosity solution having sufficient diffusion and dispersion properties using alcohol as a solvent. The amount of chloroform or benzene used to dissolve the iniferter is very small, so it does not contribute as a chain transfer or initiator, and the light absorption derived from the aromatic ring cannot compete with the progress of the polymerization, and the alcohol is present in a large excess. Among these, it is similar to the state polymerized with alcohol alone.

  The star polymer produced by this method can be used as a vector.

  Hereinafter, the present invention will be described in detail.

  In the present invention, the compound having 4 or more N, N-dialkyl-dithiocarbamylmethyl groups in the same molecule includes a benzene ring, a naphthalene ring, an anthracene ring, a biphenyl ring, a biphenylene ring, a pyridine ring, a pyrrole ring, It is preferable that four or more N, N-dialkyl-dithiocarbamylmethyl molecular groups are bonded as a branched chain to a furan ring or a pyrene ring.

  A benzene ring is preferred as an iniferter for binding a branched chain, and specific examples are as follows. That is, as the 4-branched chain, 1,2,4,5-tetrakis obtained by addition reaction of 1,2,4,5-tetrakis (bromomethyl) benzene and sodium N, N-diethyldithiocarbamate in ethanol. (N, N-diethyldithiocarbamylmethyl) benzene, and six-branched chains are hexakis (N, N, N-diethyldithiocarbamate) obtained by addition reaction of hexakis (bromomethyl) benzene and sodium N, N-diethyldithiocarbamate in ethanol. N-diethyldithiocarbamylmethyl) benzene. In particular, the latter hexakis (N, N-diethyldithiocarbamylmethyl) benzene is preferred.

  The above iniferter is almost insoluble in polar solvents such as alcohol, but is easily soluble in nonpolar solvents. The nonpolar solvent is preferably an alkyl halide or an alkylene halide, and particularly preferably chloroform or methylene chloride, especially chloroform.

As the monomer to be polymerized to this iniferter, vinyl monomers, acrylic acid derivatives, styrene derivatives and the like are suitable. Specifically, 3-N, N-dimethylaminopropylacrylamide CH ₂ ═CHCONHC ₃ H ₆ N (CH _{3 2} is preferred.

  In order to react the iniferter with the monomer, a raw material solution containing the iniferter and the monomer is prepared, and first, a reaction product in which the monomer is bonded to the iniferter is generated by the first light irradiation step.

  The concentration of the monomer in the raw material solution is preferably 70% by weight or more, for example, 70 to 99% by weight.

  The concentration of the iniferter is preferably about 10 to 1000 mM.

  The wavelength of the irradiated light is preferably 240 to 300 nm. Although the light irradiation time depends on the irradiation intensity, it is preferably about 1 to 30 minutes, particularly preferably about 1 to 5 minutes with a low irradiation intensity of about 1 μW / cm 2 to 1 mW / cm 2.

  Next, the solution containing the reaction product is diluted with an alcohol, preferably an alcohol solution of the above monomer. As the alcohol, methanol or ethanol, particularly methanol is preferable. The monomer concentration in the alcohol solution is preferably about 100 mM to 5 M as the final concentration.

  It is preferable to add 5 to 500 parts by volume of the alcohol solution to 1 part by volume of the reaction product-containing liquid from the first light irradiation step.

  The diluted solution thus diluted with the alcohol solution is subjected to the second light irradiation step, and the monomer is further polymerized with respect to the reaction product. In this case, any irradiation light source may be used as long as it includes light having a wavelength of 240 to 330 nm. For example, a low-pressure mercury lamp or a high-pressure mercury lamp can be used. The light irradiation time is preferably about 10 minutes to 120 minutes.

  Since the target branched star polymer is produced in the reaction solution by this second light irradiation, it is purified as necessary to obtain a star polymer.

  The molecular weight of the star polymer depends on the number of branched chains, but when the number of branched chains is 4, it is preferably 5,000 to 500,000, particularly 30,000 to 70,000, especially about 40,000 to 60,000. When the number of branched chains is 6, it is preferably 5,000 to 500,000, particularly 10,000 to 30,000, especially 10,000 to 20,000.

  The vector composed of the star polymer thus produced surrounds the nucleic acid as a nucleic acid-containing complex, whereby the inactivation and degradation of the nucleic acid by the enzyme in the living body can be suppressed.

  The polymer chain constituting the branched chain may have a quaternary amine on the proximal end side and a tertiary amine on the distal end side. If a quaternary amine is used in the vicinity of the nucleus to which the branched chain is bound and a tertiary amine is used around the nuclei, reduction in cytotoxicity and high efficiency of gene transfer can be expected. Quaternary amine is a cation that is an essential element of a vector, but it is cytotoxic as it is also used in bactericides and antibacterial coatings. Is advantageous.

  The polymer chain constituting the branched chain is an AB type block polymer obtained by polymerizing two or more types of monomers, that is, after polymerizing the A monomer, this polymer is isolated, and then irradiated with a system with the B monomer. However, it is preferable to use a cationic monomer at the base end portion and a nonionic hydrophilic monomer at the tip end portion. In addition, the use of a hydrophobic monomer at the tip may improve the permeability of the cell membrane and may be advantageous for gene transfer.

  The cationic polymer in the vector of the present invention may have a property that its positive charge is deactivated with time. Thus, the function of releasing nucleic acid from the nucleic acid aggregate surrounded by the vector can be imparted by deactivating the positive charge in the vector. Conditions for the nucleic acid release may be appropriately set by those skilled in the art so that the vector is released after the vector permeates the cell membrane. Examples of the cationic polymer having such a function include those in which a compound having a 4,4′-benzylidenebis (N, N-dimethylaniline) skeleton is supported on a long branched chain. A compound having a 4,4′-benzylidenebis (N, N-dimethylaniline) skeleton includes leucomalachite green, and the cationic polymer carrying the compound is cationized by light irradiation and loses a positive charge with time. It has an active property.

  In order to complex the vector comprising the star polymer and the nucleic acid, the nucleic acid may be added and mixed at room temperature with respect to a dispersion having a concentration of about 1 to 1000 μg / mL. It is preferable to add an excessive amount of a cationic polymer to the nucleic acid and to complex the cationic polymer in a saturated state with respect to the nucleic acid as a nucleic acid-containing complex.

  As the nucleic acid to be used, either DNA or RNA may be used. Preferred examples of the nucleic acid include herpes simplex virus thymidine kinase gene (HSV1-TK gene), p53 tumor suppressor gene, BRCA1 tumor suppressor gene and cytokine gene such as TNF-α gene, IL-2 gene, IL-4 gene, HLA- Cytokine genes such as B7 / IL-2 gene, HLA-B7 / B2M gene, IL-7 gene, GM-CSF gene, IFN-γ gene and IL-12 gene, and gp-100, MART-1 and MAGE-1 These cancer antigen peptide genes can be used for cancer treatment.

  In addition, cytokine genes such as VEGF gene, HGF gene and FGF gene, c-myc antisense, c-myb antisense, cdc2 kinase antisense, PCNA antisense, E2F decoy and p21 (sdi-1) gene are used for vascular treatment. Available. Such a series of genes is well known to those skilled in the art.

  It can also be used for mRNA destruction by RNA interference using double-stranded RNA of 21 to 23 bases.

  The particle size of the nucleic acid-containing complex is preferably about 50 to 400 nm. If it is smaller than this, there is a possibility that the action of the enzyme may reach the nucleic acid inside the nucleic acid-containing complex, or it may be filtered out by the kidney. Moreover, when larger than this, there exists a possibility that it may become difficult to introduce | transduce into a cell.

  The nucleic acid is used in such a form that when introduced into a cell, the function can be expressed in the cell. For example, in the case of DNA, it is used as a plasmid in which the DNA is placed so that the DNA is transcribed in the introduced cell and functionally expressed through production of the polypeptide encoded thereby. Preferably, a promoter region, a start codon, DNA encoding a protein having a desired function, a stop codon, and a terminator region are sequentially arranged.

  If desired, two or more nucleic acids can be included in one plasmid.

  In the present invention, “cells” that are desirable as a target for introduction of nucleic acids are those in which functional expression of the nucleic acids is required, and such cells can be selected variously depending on, for example, the nucleic acid used (that is, its function) Examples thereof include cardiomyocytes, smooth muscle cells, fibroblasts, skeletal muscle cells, vascular endothelial cells, bone marrow cells, bone cells, blood cell stem cells, blood cell cells and the like. In addition, monocytes, dendritic cells, macrophages, histocytes, Kupffer cells, osteoclasts, synovial A cells, microglia, Langerhans cells, epithelioid cells, multinucleated giant cells, etc., gastrointestinal epithelial cells / tubule epithelium Such as cells.

  The nucleic acid-containing complex using the vector of the present invention can be administered to a living body by any method.

  As the administration method, intravenous or intraarterial injection is particularly preferable, but intramuscular, adipose tissue, subcutaneous, intradermal, intralymphatic, intralymphatic, body cavity (pericardial cavity, thoracic cavity, abdominal cavity, cerebrospinal cavity) Etc.) In addition to administration into the bone marrow, administration into the diseased tissue is also possible.

  The pharmaceutical comprising this nucleic acid-containing complex as an active ingredient is further a pharmaceutically acceptable carrier (osmotic pressure regulator, stabilizer, preservative, solubilizer, pH adjuster, thickener, etc.) as necessary. It is possible to mix with. Any known carrier can be used.

  Moreover, the medicine containing this nucleic acid-containing complex as an active ingredient also includes those containing two or more nucleic acid-containing complexes with different types of nucleic acids. Such a medicine having a plurality of therapeutic purposes is particularly useful in the field of diversifying gene therapy.

  As for the dosage, the dosage administered to animals, particularly humans, varies depending on various factors such as the target nucleic acid, the method of administration, and the specific site to be treated. However, the dosage should be sufficient to produce a therapeutic response.

  This nucleic acid-containing complex is preferably applied to gene therapy. Applicable diseases vary depending on the type of nucleic acid included in the complex, but in addition to diseases in the cardiovascular region that cause lesions such as peripheral arterial disease, coronary artery disease, restenosis after arterial dilation, cancer (malignant Melanoma, brain tumor, metastatic malignant tumor, breast cancer, etc.), infectious diseases (HIV, etc.), single genetic diseases (cystic fibrosis, chronic granulomas, α1-antitrypsin deficiency, Gaucher disease, etc.) .

Example 1
[Composition of Iniferter]
First, an iniferter composed of hexakis (N, N-diethyldithiocarbamatemilmethyl) benzene was synthesized according to the following reaction formula (Chemical Formula 1).

Hexakis (bromomethyl) benzene, which is a six-branch type raw material, is hardly soluble in all solvents, and thus was synthesized by eliminating NaBr in ethanol by solid / liquid contact (see FIG. 1 for the reaction formula). A 30-fold molar amount of NaSCSN (Et) ₂ was added to 5 g of hexakis (bromomethyl) benzene, and the mixture was stirred in 1000 mL of ethanol at room temperature. The end point of the reaction was confirmed by TLC, and stirring was continued until no raw material components were confirmed. It took 5 days to complete. The obtained iniferter could be recrystallized with chloroform. The structure of the synthesized iniferter was confirmed by NMR (see FIG. 5).

[Purification of monomer]
The monomer 3-N, N-dimethylaminopropylacrylamide (DMAPAAm) was purified by distillation under reduced pressure. When the oil bath temperature was about 100 ° C., the quinoline compound as an inhibitor was precipitated, so that cooling water was not passed through Liebig, but it was heated with a hair dryer to induce volatile components to a vacuum trap. After no volatile components were observed, the decompression was stopped, and the interior of the distillation system such as Liebig and the To-tube was washed with chloroform to remove quinoline-based substances adhering to the tube wall. After DMAPAAm volatilization started (oil bath temperature was about 150 ° C.), fractions of 110 ° C. to 115 ° C. were collected. Distillation was stopped by lowering the oil bath temperature, and evacuation was continued for 10 minutes before returning to normal pressure. The operation of returning to normal pressure was performed with nitrogen gas, and the purified DMAPAAm was used immediately for polymerization without being stored.

[Photopolymerization]
First light irradiation step Iniferter (0.06 g, final concentration 1 mM) is wetted with about 200 μL of chloroform, mixed with 4.0 mL of DMAPAAm, put into a quartz cell (10 mm cell length), and 276 nm monochromatic light (about 1 μW / cm ² ) was irradiated for 5 minutes.

Dilution step DMAPAAm (final concentration of about 5 g = 0.1 M to about 80 g = 1.5 M) was mixed with methanol, the whole amount was mixed with 350 mL of methanol, and nitrogen gas bubbling was performed for 1 hour. 4 mL of the solution irradiated with 276 nm monochromatic light (about 1 μW / cm ² ) for 5 minutes was mixed and diluted.

Second Light Irradiation Step This diluted solution was irradiated with light with a high-pressure mercury lamp, and photopolymerization was performed for 30 minutes. At the end of the reaction, a faint pale yellow coloration and thickening was observed.

[Polymer purification]
The polymerization solution was evaporated to remove methanol, and the resulting solution was dropped into diethyl ether to reprecipitate the polymer. The precipitate was dissolved in methanol, filtered through # 2 filter paper, then dropped into diethyl ether and reprecipitated. This was left for 24 hours to completely precipitate the polymer. Thereafter, reprecipitation was further performed twice with a chloroform / diethyl ether system. The obtained purified polymer was dissolved in water, the remaining organic solvent was removed with an evaporator, filtered through a 0.2 μm membrane filter, and freeze-dried to obtain a 6-branched star polymer. The product was confirmed by NMR. The molecular weight was measured by GPC. The molecular weight could be freely controlled by setting the polymerization conditions mainly of the polymerization time.

Comparative Example 1
As a comparative example, iniferter was dissolved in chloroform, DMAPAAm was mixed with chloroform, and photopolymerization was performed with chloroform for a total amount of 350 mL. As a result, although the molecular weight increased depending on the monomer concentration and polymerization time, the molecular weight reached a peak at about 18000, and a polymer having a molecular weight higher than that could not be obtained.

It is a graph which shows the result of a comparative example. It is a graph which shows the result of a comparative example. It is a graph which shows the result of a comparative example. It is a graph which shows the result of an Example. NMR of iniferter.

Claims (14)

A method for synthesizing a star polymer by light irradiation living polymerization using a compound having four or more N, N-dialkyl-dithiocarbamylmethyl molecular groups in the same molecule as an iniferter,
A step of preparing a raw material solution obtained by dissolving a monomer and an iniferter in a nonpolar solvent;
A first light irradiation step of irradiating the raw material solution with light;
A dilution step of diluting the light irradiated solution with alcohol;
And a second light irradiation step of irradiating the diluted solution with light.   In Claim 1, the compound having 4 or more N, N-dialkyl-dithiocarbamylmethyl molecular groups in the same molecule is a benzene ring, naphthalene ring, anthracene ring, biphenyl ring, biphenylene ring, pyridine ring, pyrrole ring, A method for synthesizing a star polymer, characterized in that a furan ring or a pyrene ring is used as a nucleus, and four or more N, N-dialkyl-dithiocarbamylmethyl molecular groups are bonded as a branched chain to the nucleus.   3. The method for synthesizing a star polymer according to claim 1, wherein the monomer is a vinyl monomer.   4. The method for synthesizing a star polymer according to claim 3, wherein the vinyl monomer is 3-N, N-dimethylaminopropylacrylamide.   5. The method for synthesizing a star polymer according to claim 4, wherein the solvent is an alkyl halide or an alkylene halide.   5. The method for synthesizing a star polymer according to claim 4, wherein the solvent is chloroform, carbon tetrachloride or methylene chloride.   5. The method for synthesizing a star polymer according to claim 4, wherein the solvent is chloroform.   The method for synthesizing a star polymer according to any one of claims 1 to 7, wherein a monomer concentration in the raw material solution is 70% by weight or more.   The method for synthesizing a star polymer according to any one of claims 1 to 8, wherein the wavelength of light in the first light irradiation step is 240 to 300 nm.   The method for synthesizing a star polymer according to any one of claims 1 to 9, wherein the alcohol is methanol.   The method for synthesizing a star polymer according to any one of claims 1 to 10, wherein the alcohol is an alcohol solution of the monomer.   A star polymer synthesized by the method according to claim 1.   A star-type polymer obtained by additionally polymerizing the star-type polymer according to claim 12 with a vinyl monomer different from the monomer used for the star-type polymer monomer.   A vector comprising the star polymer according to claim 12 or 13.

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