JP2017226791A - Resin composition - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a resin composition having excellent safety for human bodies and the environment and excellent hemolytic resistance and a medical resin composition having excellent safety for human bodies and the environment and excellent hemolytic resistance.SOLUTION: A resin composition contains a polymer having a functional group in at least one molecular terminal, and iodine. The amount of the iodine is 0.01-5000 ppm relative to the mass of the polymer, and the amount of heavy metal in the resin composition is 1 ppm or less relative to the mass of the polymer.SELECTED DRAWING: None

Description

  The present invention relates to a resin composition. More specifically, the present invention relates to, for example, a resin composition and a medical resin composition useful as a pharmaceutical carrier, a coating agent or the like used when holding a drug and introducing it into the body orally or via blood. And a method for producing a polymer used in the resin composition. The resin composition and the medical resin composition of the present invention are expected to be used as biocompatible medical materials such as an injectable drug carrier and an orally administered drug carrier.

  As a method for producing a polymer used in a medical resin composition, a living radical polymerization method using a catalyst having carbon as a central element (see, for example, Patent Document 1) and a nonmetallic element having an ionic bond with a halide ion A living radical polymerization method (for example, see Patent Document 2) using a catalyst composed of a compound has been proposed.

  The catalysts used in the living radical polymerization method are all low in toxicity, low in use amount and high in solubility, are colorless and odorless, and are excellent in safety to the human body and the environment.

  However, in recent years, development of a resin composition and a medical resin composition that are excellent in safety with respect to the human body and the environment and excellent in hemolysis resistance has been desired.

International Publication No. 2010/027093 Pamphlet International Publication No. 2013/027419 Pamphlet

  This invention is made | formed in view of the said prior art, and it aims at providing the resin composition and medical resin composition which were excellent in the safety with respect to a human body and an environment, and excellent in hemolysis resistance.

The present invention
(1) A resin composition containing a polymer having a functional group at at least one molecular terminal and iodine, wherein the amount of the iodine is 0.01 to 5000 ppm with respect to the mass of the polymer, A resin composition, wherein the amount of heavy metal in the composition is 1 ppm or less with respect to the mass of the polymer;
(2) A medical resin composition comprising a polymer having a functional group at at least one molecular terminal and iodine, wherein the amount of iodine is 0.01 to 5000 ppm based on the mass of the polymer; The amount of heavy metal in the medical resin composition is 1 ppm or less with respect to the mass of the polymer,
(3) A method for producing a polymer having a functional group at at least one molecular end, wherein (A1) an organic iodine compound having a functional group and (B) a radical is generated as a catalyst from the organic iodine compound. At least one molecular terminal characterized by polymerizing a radical polymerizable monomer in the presence of a compound that extracts iodine, or a compound that coordinates to iodine of the organic iodine compound and extracts iodine from the organic iodine compound A method for producing a polymer having a functional group in
(4) A method for producing a polymer having a functional group at at least one molecular end, wherein (A2) an organic iodine compound, and (B) a compound that generates radicals as a catalyst and extracts iodine from the organic iodine compound. Or a step of polymerizing a radical polymerizable monomer in the presence of a compound that coordinates to iodine of the organic iodine compound and extracts iodine from the organic iodine compound, and at least one molecular terminal of the obtained polymer A process for producing a polymer having a functional group at at least one molecular end, which comprises a step of introducing a functional group into
(5) A method for producing a biocompatible medical polymer having a functional group at at least one molecular end, wherein (A1) an organic iodine compound having a functional group and (B) generating a radical as a catalyst Polymerizing a biocompatible radical polymerizable monomer in the presence of a compound that extracts iodine from the organic iodine compound, or a compound that coordinates to iodine of the organic iodine compound and extracts iodine from the organic iodine compound; A method for producing a biocompatible medical polymer having a functional group at at least one molecular end, and (6) a method for producing a biocompatible medical polymer having a functional group at at least one molecular end. And (A2) an organic iodine compound, and (B) a compound that generates radicals as a catalyst to extract iodine from the organic iodine compound, Is a step of polymerizing a biocompatible radical polymerizable monomer in the presence of a compound that coordinates to iodine of the organic iodine compound and extracts iodine from the organic iodine compound; And a method for producing a biocompatible medical polymer having a functional group at at least one molecular end, wherein the functional group is introduced into at least one molecular end of the polymer.

  ADVANTAGE OF THE INVENTION According to this invention, while being excellent in the safety | security with respect to a human body and an environment, the resin composition and medical resin composition excellent in hemolysis resistance are provided.

  Hereinafter, the present invention will be described in detail. A combination of two or more preferred embodiments of the present invention described below is also a preferred embodiment of the present invention.

  The resin composition of the present invention is a resin composition containing a polymer having a functional group at at least one molecular end and iodine, as described above, and the amount of iodine is 0 with respect to the mass of the polymer. 0.01 to 5000 ppm, and the amount of heavy metal in the resin composition is 1 ppm or less based on the mass of the polymer. The medical resin composition of the present invention is a medical resin composition containing a polymer having a functional group at at least one molecular terminal and iodine, and the amount of the iodine is based on the mass of the polymer. It is 0.01-5000 ppm, The quantity of the heavy metal in the said medical resin composition is 1 ppm or less with respect to the mass of the said polymer, It is characterized by the above-mentioned.

  Since both the resin composition and the medical resin composition of the present invention have the above-described constituent requirements, they are excellent in safety to human bodies and the environment, and excellent in hemolysis resistance.

  Examples of the polymer having a functional group at at least one molecular terminal include a homopolymer of a radical polymerizable monomer and a copolymer of two or more kinds of radical polymerizable monomers. Is not limited to such examples.

As the functional group introduced into at least one molecular end of the polymer, an anionic functional group, a cationic functional group, a nonionic functional group, and an amphoteric functional group are preferable. The functional group is preferably a reactive functional group from the viewpoint of modifying a drug or the like. Suitable functional groups include, for example, a group represented by the formula: —COOM (M represents a hydrogen atom or an alkali metal atom), a hydroxyl group, an allyl group, an epoxy group, an aldehyde group, an —NH ₂ group, a CONH— group, Although -SH group etc. are mentioned, this invention is not limited only to this illustration. Examples of M include alkali metal atoms such as sodium atom and potassium atom. The number of functional groups in the polymer having a functional group is not particularly limited, but usually 1 to 6 is preferable.

As a method for producing a polymer having a functional group at at least one molecular end, for example,
(X) (A1) an organic iodine compound having a functional group, and (B) a compound that generates radicals as a catalyst to extract iodine from the organic iodine compound, or the organic iodine compound coordinated with iodine of the organic iodine compound A method of polymerizing a radical polymerizable monomer in the presence of a compound that extracts iodine from the compound (hereinafter referred to as method X),
(Y) (A2) an organic iodine compound, and (B) a compound that generates a radical as a catalyst and extracts iodine from the organic iodine compound, or coordinates with iodine of the organic iodine compound and generates iodine from the organic iodine compound. A method comprising a step of polymerizing a radical polymerizable monomer in the presence of a compound to be extracted and a step of introducing a functional group into at least one molecular terminal of the obtained polymer (hereinafter referred to as method Y),
However, the present invention is not limited to such examples.

  The radical polymerizable monomer used in the method X includes a biocompatible radical polymerizable monomer (hereinafter referred to as a biocompatible monomer) and a radical polymerizable monomer other than the biocompatible monomer. Is mentioned. These radically polymerizable monomers may be used alone or in combination of two or more. When a biocompatible monomer is used as the radical polymerizable monomer, for example, a biocompatible medical polymer can be obtained.

  Examples of the biocompatible monomer include a polyoxyalkylene group-containing monomer, a hydroxyl group-containing (meth) acrylate, an alkoxyalkyl (meth) acrylate, and a vinyl monomer. It is not limited. These biocompatible monomers may be used alone or in combination of two or more.

  In the present invention, “(meth) acrylate” means acrylate or methacrylate, and acrylate and methacrylate may be used alone or in combination. “(Meth) acryl” means acrylic or methacrylic.

  Examples of the polyoxyalkylene group-containing unsaturated monomer include, for example, the formula (I):

Wherein R ¹ , R ² and R ³ are each independently a hydrogen atom or a methyl group, R ⁴ is an alkylene group having 2 to 18 carbon atoms, and R ⁵ is a hydrogen atom or 1 to 20 carbon atoms. A hydrocarbon group, X is a divalent alkylene group having 1 to 5 carbon atoms, a —CO— group or a direct bond when the R ¹ R ³ C═CR ² — group is a vinyl group, m is — (R ⁴ O) is the average number of moles of the group added and represents a number from 1 to 300)
The polyoxyalkylene group containing unsaturated monomer represented by these, etc. are mentioned.

In addition, when two or more types of oxyalkylene groups represented by the formula: —R ⁴ O— are present in one molecule, the oxyalkylene groups may be random, block, or alternating.

In the formula (I), R ⁵ is a hydrogen atom or a hydrocarbon group having 1 to 20 carbon atoms. Among R ⁵ , a hydrogen atom and a hydrocarbon group having 1 to 20 carbon atoms are preferable, a hydrocarbon group having 1 to 10 carbon atoms is more preferable, a hydrocarbon group having 1 to 3 carbon atoms is still more preferable, More preferred are 1 or 2 hydrocarbon groups. Among the hydrocarbon groups, a saturated alkyl group and an unsaturated alkyl group are preferable, a saturated alkyl group having 1 to 20 carbon atoms is more preferable, a saturated alkyl group having 1 to 10 carbon atoms is further preferable, and a carbon number having 1 to 3 is preferable. Saturated alkyl groups are even more preferred.

In the formula (I), the oxyalkylene group represented by the formula: —R ⁴ O— is an oxyalkylene group having 2 to 18 carbon atoms. Examples of the oxyalkylene group include an oxyethylene group, an oxypropylene group, an oxybutylene group, an oxyisobutylene group, an oxy-1-butene group, and an oxy-2-butene group, but the present invention is only such examples. It is not limited to. Among these oxyalkylene groups, an oxyalkylene group having 2 to 8 carbon atoms is preferable, and an oxyalkylene group having 2 to 4 carbon atoms such as an oxyethylene group, an oxypropylene group, and an oxybutylene group is more preferable. Is more preferable.

In the formula (I), when the oxyalkylene group represented by the formula: —R ⁴ O— contains an oxyethylene group, it preferably contains 50 mol or more of oxyethylene group with respect to 100 mol of oxyalkylene group, More preferably, it is more preferably 90 mol or more.

In the formula (I), m is the average added mole number of the oxyalkylene group represented by the formula: —R ⁴ O—. The average added mole number means the average value of the number of moles of oxyalkylene groups in 1 mole of polyoxyalkylene group-containing unsaturated monomer. The lower limit of m is preferably 2 or more, more preferably 4 or more, and still more preferably 8 or more. The upper limit of m is preferably 100 or less, more preferably 50 or less.

X is a direct bond when the C 1-5 divalent alkylene group, —CO— group, or R ¹ R ³ C═CR ² — group is a vinyl group. Of these groups, the —CO— group is preferred.

  Examples of the polyoxyalkylene group-containing unsaturated monomer include unsaturated alcohol polyalkylene glycol adducts, polyalkylene glycol ester monomers, (alkoxy) polyalkylene glycol monomaleic acid esters, and the like.

  An unsaturated alcohol polyalkylene glycol adduct is a compound in which a polyalkylene glycol chain is added to an alcohol having an unsaturated group.

  Examples of the unsaturated alcohol polyalkylene glycol adduct include polyethylene glycol monovinyl ether, polyethylene glycol monoallyl ether, polyethylene glycol mono (2-methyl-2-propenyl) ether, polyethylene glycol mono (2-butenyl) ether, polyethylene Glycol mono (3-methyl-3-butenyl) ether, polyethylene glycol mono (3-methyl-2-butenyl) ether, polyethylene glycol mono (2-methyl-3-butenyl) ether, polyethylene glycol mono (2-methyl-2) -Butenyl) ether, polyethylene glycol mono (1,1-dimethyl-2-propenyl) ether, polyethylene polypropylene glycol mono (3-methyl-3-butenyl) Ether, the like methoxy polyethylene glycol mono (3-methyl-3-butenyl) ether, present invention is not limited only to those exemplified.

  The polyalkylene glycol ester monomer is a monomer in which an unsaturated group and a polyalkylene glycol chain are bonded through an ester bond.

  As the polyalkylene glycol ester-based monomer, for example, an esterified product of an alkoxy polyalkylene glycol obtained by adding 1 to 300 mol of an oxyalkylene group having 2 to 18 carbon atoms to an alcohol and (meth) acrylic acid is preferable. Among the alkoxypolyalkylene glycols, those having an oxyethylene group as a main component are preferable. Examples of the alcohol include methanol, ethanol, 1-propanol, 2-propanol, 1-butanol, 2-butanol, 1-pentanol, 2-pentanol, 3-pentanol, 1-hexanol, 2-hexanol, C1-C30 aliphatic alcohols such as 3-hexanol, octanol, 2-ethyl-1-hexanol, nonyl alcohol, lauryl alcohol, cetyl alcohol, stearyl alcohol, and C3-C30 alicyclics such as cyclohexanol Examples thereof include unsaturated alcohols having 3 to 30 carbon atoms such as alcohol, (meth) allyl alcohol, 3-buten-1-ol, and 3-methyl-3-buten-1-ol, which are used alone. Two or more types may be used in combination. Examples of the esterified product include methoxy polyethylene glycol mono (meth) acrylate, methoxy (polyethylene glycol polypropylene glycol) mono (meth) acrylate, methoxy (polyethylene glycol polybutylene glycol) mono (meth) acrylate, and methoxy (polyethylene glycol polypropylene glycol). Polybutylene glycol) mono (meth) acrylate and the like, and these may be used alone or in combination of two or more.

  Among the polyalkylene glycol ester monomers, for example, (alkoxy) polyalkylene glycol mono (meth) acrylates such as methoxypolyethylene glycol monomethacrylate are preferable.

  Examples of the hydroxyl group-containing (meth) acrylate include hydroxyalkyl (meth) acrylates having 2 to 4 carbon atoms of hydroxyalkyl groups such as 2-hydroxyethyl acrylate and 2-hydroxyethyl methacrylate, glycerin acrylate, and glycerin methacrylate. However, the present invention is not limited to such examples. These hydroxyl group-containing (meth) acrylates may be used alone or in combination of two or more.

  Examples of the alkoxyalkyl (meth) acrylate include methoxymethyl (meth) acrylate, methoxyethyl (meth) acrylate, methoxypropyl (meth) acrylate, ethoxymethyl (meth) acrylate, ethoxyethyl (meth) acrylate, ethoxypropyl ( Examples include alkoxyalkyl (meth) acrylates in which the alkoxy group such as (meth) acrylate has 1 to 4 carbon atoms and the alkyl group has 1 to 4 carbon atoms, but the present invention is limited to such examples only. It is not something. These alkoxyalkyl (meth) acrylates may be used alone or in combination of two or more.

  The vinyl monomer is a biocompatible compound having a vinyl group other than a polyoxyalkylene group-containing monomer, a hydroxyl group-containing (meth) acrylate, and an alkoxyalkyl (meth) acrylate. As the vinyl monomer, for example, Phosphorylcholine group-containing monomers such as 2- (meth) acryloyloxymethyl phosphorylcholine and 2- (meth) acryloyloxyethyl phosphorylcholine, tetrahydrofurfuryl (meth) acrylate, isopropylacrylamide, vinyl alcohol, vinylformamide, vinylisobutylacrylamide, ( Examples include meth) acrylamide, dimethylacrylamide, vinylacetamide, N-vinylpyrrolidone, and the like, but the present invention is not limited to such examples. These vinyl monomers may be used alone or in combination of two or more.

  Among the biocompatible monomers, polyoxyalkylene group-containing unsaturated monomers, hydroxyalkyl (meth) acrylates having 2 to 4 carbon atoms in the hydroxyalkyl group, and alkoxy groups having 1 to 4 carbon atoms. Preferred are alkoxyalkyl acrylates having 1 to 4 carbon atoms in the alkyl group and tetrahydrofurfuryl (meth) acrylate, polyoxyalkylene group-containing unsaturated monomers, methoxyethyl acrylate, 2-hydroxyethyl (meth) acrylate N-vinylpyrrolidone, 2- (meth) acryloyloxyethyl phosphorylcholine and tetrahydrofurfuryl (meth) acrylate are more preferred, and methoxyethyl acrylate and 2-hydroxyethyl methacrylate are more preferred.

  In addition, the said biocompatible monomer can use together the other monomer copolymerizable with a biocompatible monomer within the range which does not inhibit the objective of invention. Examples of the other monomer copolymerizable with the biocompatible monomer include those similar to radical polymerizable monomers other than the biocompatible monomer described later.

  Examples of the radical polymerizable monomer other than the biocompatible monomer include aziridines, (meth) acrylic acid, methyl (meth) acrylate, ethyl (meth) acrylate, propyl (meth) acrylate, n-butyl ( (Meth) acrylate, isobutyl (meth) acrylate, tert-butyl (meth) acrylate, 2-ethylhexyl (meth) acrylate, diaminomethyl (meth) acrylate, diaminoethyl (meth) acrylate, dimethylamino (meth) acrylate, diethylamino (meth) ) Acrylate, dimethylaminomethyl (meth) acrylate, dimethylaminoethyl (meth) acrylate, glycidyl (meth) acrylate, styrene and the like, but the present invention is not limited to such examples. These radically polymerizable monomers other than these biocompatible monomers may be used alone or in combination of two or more.

  The content of the biocompatible monomer in the radical polymerizable monomer is preferably 30 mol% with respect to 100 mol% of the radical polymerizable monomer from the viewpoint of improving the biocompatibility of the resulting polymer. Above, more preferably 50 mol% or more, still more preferably 80 mol% or more, still more preferably 90 mol% or more, still more preferably 100 mol%.

  In the method X, (A1) an organic iodine compound having a functional group, (B) a compound that generates radicals as a catalyst and extracts iodine from the organic iodine compound, or is coordinated with iodine of the organic iodine compound and the organic It is characterized by living radical polymerization of a radical polymerizable monomer in the presence of a compound that extracts iodine from an iodine compound. The living radical polymerization may be bulk polymerization without using a solvent, or may be solution polymerization. Moreover, emulsion polymerization, dispersion polymerization, suspension polymerization, etc. can also be performed by using the solvent which is not mixed with the radically polymerizable monomer. For example, when styrene, methacrylate, or the like is used as the radical polymerizable monomer, emulsion polymerization, dispersion polymerization, suspension polymerization, or the like can be performed using water as a solvent.

As a specific example of the method X, for example,
(1) A method of living radical polymerization of a radically polymerizable monomer in the presence of (A1) an organic iodine compound having a functional group and (B) a catalyst;
(2) (A1) Presence of an organic iodine compound having a functional group, which is a reaction product obtained by reacting iodine with an azo compound having a functional group as an organic iodine compound having a functional group, and (B) a catalyst Although the method of carrying out a living radical polymerization of the radically polymerizable monomer below is mentioned, this invention is not limited only to this illustration.

  Solvents used for solution polymerization of radically polymerizable monomers include, for example, water; aromatic solvents such as benzene, toluene, and xylene; methanol, ethanol, isopropanol, n-butanol, tert-butyl alcohol, and the like. Alcohol solvents; halogen atom-containing solvents such as dichloroethane, dichloromethane, chloroform; ether solvents such as propylene glycol methyl ether, dipropylene glycol methyl ether, ethyl cellosolve, butyl cellosolve, diglyme; esters such as ethyl acetate, butyl acetate, cellosolve Solvents: ketone solvents such as acetone, methyl ethyl ketone, methyl isobutyl ketone, diacetone alcohol; organic solvents such as amide solvents such as dimethylformamide But the present invention is not limited only to those exemplified. These solvents may be used alone or in combination of two or more. The amount of the solvent may be appropriately determined in consideration of the polymerization conditions, the monomer composition, the concentration of the resulting polymer, and the like.

  (A1) The organic iodine compound having a functional group is not particularly limited, and can be appropriately selected from organic iodine compounds that can be generally used. Examples of the organic iodine compound having a functional group include 2-iodoisobutyric acid, 2-iodo-2-phenylacetic acid, 2-hydroxyethyl-2-iodoisobutyric acid salt, and 2-hydroxyethyl-2-iodo-2-phenylacetic acid. Salt, 2-iodo-2-amidinopropane, 4-iodo-4-cyano-pentanoic acid, 2-iodo-2-methylpropanamide, 2-iodo-2-cyanobutanol, 2-iodo-2-methyl-N -(2-hydroxyethyl) propionamide 4-methylpentane, 2-iodo-2-methyl-N- (1,1-bis (hydroxymethyl) -2-hydroxyethyl) propionamide 4-methylpentane, iodoacetic acid, Examples thereof include alkyl iodide having a substituent such as 2-iodopropanoic acid and 2-iodopropanamide. , It is not limited only to those exemplified.

  An organic iodine compound having a functional group is charged with the raw material, and an organic iodine compound having a functional group is generated in situ during polymerization, that is, in a reaction solution, and used as an organic iodine compound having a functional group in this polymerization method. You can also For example, an azo compound having a functional group and iodine are charged as raw materials, and an organic iodine compound having a functional group is generated in situ during the polymerization by the reaction between the two, and this is an organic iodine compound having a functional group of this polymerization method. Can be used as That is, the production method of the present invention may include a step of reacting iodine with an azo compound having a functional group to produce an organic iodine compound having a functional group.

  As an azo compound having a functional group used for generating an organic iodine compound having a functional group, for example, an azo compound having a functional group as an azo radical polymerization initiator can be used.

  Examples of the azo compound having a functional group include 4,4′-azobis (4-cyanopentanoic acid), 2,2′-azobis [2-methyl-N- [1,1-bis (hydroxymethyl) -2]. -Hydroxyethyl] propionamide], 2,2′-azobis [N- (2-hydroxyethyl) -2-methoxypropanamide], 2,2′-azobis (2-methyl-2-propenylpropanamide), 2 , 2′-bis (2-imidazolin-2-yl) [2,2′-azobispropane] dihydrochloride, 2,2′-azobis (propane-2-carbomidine) dihydrochloride, 2,2 ′ -Azobis [N- (2-carboxyethyl) -2-methylpropionamidine], 2,2'-azobis [2- [1- (2-hydroxyethyl) -2-imidazolin-2-yl] propane disalt Salt, 2,2′-azobis [2-methyl-N-2-propenylpropanamide], 2,2′-azobis [2- (2-imidazolin-2-yl) propane] dihydrochloride, and the like. The present invention is not limited to such examples.

  The organic iodine compound having a functional group can be used by being immobilized on a surface such as an inorganic or organic solid surface, an inorganic or organic molecular surface, or the like. For example, an organic halide can be immobilized on a silicon substrate surface, a polymer film surface, an inorganic or organic fine particle surface, a pigment surface, or the like. For immobilization, for example, a chemical bond or a physical bond can be used.

  The amount of the azo compound having a functional group used for generating the organic iodine compound having a functional group is 1 mol or more per 1 mol of iodine because the production of the organic iodine compound having a functional group is efficient. Preferably, 1.3 mol or more is more preferable. Further, in consideration of the fact that after the formation of the organic iodine compound having a functional group, the azo compound having an unreacted functional group acts as a radical polymerization initiator, 5 mol or less is preferable with respect to 1 mol of iodine, and 3 mol or less. Is more preferable.

  The amount of the organic iodine compound having a functional group is preferably 0.1 mol or more and more preferably 0.5 mol or more with respect to 100 mol of the radical polymerizable monomer used from the viewpoint of polymerization control. Moreover, from a viewpoint of a polymerization degree, 50 mol or less is preferable, 40 mol or less is more preferable, and 10 mol or less is further more preferable.

  The amount of the organic iodine compound having a functional group per 100 parts by mass of the radical polymerizable monomer is preferably 0.01 parts by mass or more, more preferably 0.1 parts by mass from the viewpoint of improving hemolysis resistance. Above, more preferably 1 part by mass or more, and from the viewpoint of improving safety to human body and environment, preferably 50 parts by mass or less, more preferably 20 parts by mass or less, still more preferably 10 parts by mass or less, and even more preferably. Is 5 parts by mass or less.

  When the organic iodine compound having a functional group is not isolated but is generated in-situ, the amount of the organic iodine compound having a functional group can be calculated from the amount of iodine used.

  Examples of the catalyst (B) include a compound that generates radicals and extracts iodine from the organic iodine compound, and a compound that coordinates with iodine of the organic iodine compound and extracts iodine from the organic iodine compound.

  Examples of the compound that generates radicals and extracts iodine from the organic iodine compound include phosphorus, nitrogen, carbon, oxygen, germanium, tin, and antimony that are used in reversible transfer catalyst polymerization (RTCP method). Examples include a catalyst made of a compound containing at least one selected central element and an iodine atom bonded to the central element, but the present invention is not limited to such examples.

  Examples of the catalyst used as a central element selected from germanium, tin, or antimony include, for example, at least one central element selected from germanium, tin, or antimony, and at least one iodine atom bonded to the central element. Examples thereof include germanium (II) iodide, germanium (IV) iodide, tin (II) iodide, and tin (IV) iodide (see JP 2007-92014 A). ). These catalysts may be used alone or in combination of two or more.

  Examples of the catalyst having nitrogen or phosphorus as a central element include compounds containing at least one central element selected from nitrogen or phosphorus and at least one iodine atom bonded to the central element. Specifically, Phosphorus halides such as phosphorus iodide; phosphite compounds such as phosphine iodide; phosphinate compounds such as ethoxyphenyl phosphinate and phenylphenoxyphosphinate; nitrogen iodide, iodophosphorous acid, amine iodide, Examples thereof include iodinated imide derivatives such as iodosuccinimide; hydantoin compounds (see International Publication No. 2008/139980). These catalysts may be used alone or in combination of two or more.

  Specific examples of the catalyst having carbon as a central element include, for example, iodobenzene, 4-methyl-1-iodobenzene, 2,4,6-trimethyliodobenzene, 3-cyanoiodobenzene, 4-cyanoiodobenzene, 4 -Iodoanisole, tetraiodomethane, trifluoroiodomethane, difluorodiiodomethane, 1,4-cyclohexadiene, diphenylmethane, dimesitylmethane, xanthene, thioxanthene, diethyl malonate, fluorene; acetoacetyl compounds such as acetylacetone However, the present invention is not limited to such examples. These catalysts may be used alone or in combination of two or more.

  Specific examples of the oxygen-centered catalyst include phenolic compounds such as phenol, hydroquinone and tert-butylphenol; iodooxyphenyl compounds such as thymol diiodide; vitamins such as vitamin E, and the like. The present invention is not limited to such examples. These catalysts may be used alone or in combination of two or more.

  Examples of the compound that coordinates to iodine of the organic iodine compound and extracts iodine from the organic iodine compound include an organic amine compound used in reversible complex formation mediated polymerization (RCMP), and an ionic bond with iodide ion. Examples of the non-metallic compound include a catalyst in which the non-metallic atom in the non-metallic compound is in a cation state and forms an ionic bond with an iodide ion. However, the present invention is limited only to such examples. Is not to be done.

  Specific examples of the catalyst comprising an organic amine compound include triethylamine, tributylamine, 1,1,2,2-tetrakis (dimethylamino) ethene, 1,4,8,11-tetramethyl-1,4,8, 11-tetraazacyclotetradecane, ethylenediamine, tetramethylethylenediamine, tetramethyldiaminomethane, tris (2-aminoethyl) amine, tris (2- (methylamino) ethyl) amine, hematoporphyrin, and the like (International Publication 2011) / Ref. 016166 pamphlet). These catalysts may be used alone or in combination of two or more.

  As a catalyst which is a nonmetallic compound having an ionic bond with an iodide ion, the nonmetallic atom in the nonmetallic compound is in a cation state, and specifically forms an ionic bond with an iodide ion. Includes ammonium salt, imidazolium salt, pyridinium salt, phosphonium salt, sulfonium salt, iodonium salt, and more specifically, tetrabutylammonium iodide, tetrabutylammonium triiodide, tetrabutylammonium bromodiiodide, 1-methyl-3-methyl-imidazolium iodide, 2-chloro-1-methylpyridinium iodide, methyltributylphosphonium iodide, tetraphenylphosphonium iodide, tributylsulfonium iodide, diphenyliodonium iodide, etc. Country See pamphlet Publication No. 2013/027419). These catalysts may be used alone or in combination of two or more.

  The amount of the (B) catalyst is preferably 0.01 to 100 mol of the organic iodine compound having a functional group (A1) from the viewpoint of increasing the polymerization rate and reducing the remaining amount of the unreacted monomer. It is 50 mol, More preferably, it is 0.05-30 mol, More preferably, it is 0.1 mol-20 mol.

  In addition, the amount of the (B) catalyst per 100 parts by mass of the radical polymerizable monomer is preferably 0.01 parts by mass or more, more preferably 0.1 parts by mass or more from the viewpoint of improving hemolysis resistance. From the viewpoint of improving safety to the human body and the environment, it is preferably 50 parts by mass or less, more preferably 20 parts by mass or less, still more preferably 10 parts by mass or less, and even more preferably 5 parts by mass or less.

  In the method X, when a radical polymerizable monomer is polymerized, a polymerization initiator is used when (B) a compound that generates radicals and extracts iodine from the organic iodine compound is used as a catalyst. When the radical polymerizable monomer is polymerized, when (B) a compound that coordinates with iodine of the organic iodine compound and extracts iodine from the organic iodine compound is used as a catalyst, a polymerization initiator is used. Although the polymerization reaction can be carried out without using it, a small amount of a polymerization initiator may be used if necessary.

  Examples of the polymerization initiator include an azo radical polymerization initiator and a peroxide radical polymerization initiator, but the present invention is not limited to such examples. These polymerization initiators may be used alone or in combination of two or more.

  Examples of the azo radical polymerization initiator include 2,2′-azobis (4-methoxy-2,4-dimethylvaleronitrile), dimethyl-2,2′-azobisisobutyrate, and 2,2′-azobis. (Isobutyronitrile) (AIBN), 2,2′-azobis (2,4-dimethylvaleronitrile), 2,2′-azobis (2-methylbutyronitrile) and the like can be mentioned. It is not limited only to such illustration. These azo radical polymerization initiators may be used alone or in combination of two or more. As the azo radical polymerization initiator, an azo compound having a functional group used for generating the organic iodine compound having the functional group can be used.

  The peroxide radical polymerization initiator is preferably an organic peroxide radical polymerization initiator. Examples of the organic peroxide radical polymerization initiator include benzoyl peroxide, dicumyl peroxide, tert-butylperoxybenzoate (BPB), 1,1-bis (tert-butylperoxy) -3,3, Examples include 5-trimethylcyclohexane, di (4-tert-butylcyclohexyl) peroxydicarbonate, tert-butylperoxy-2-ethylhexanoate, ditert-butyl peroxide, cyclohexanone peroxide, and acetylacetone peroxide. However, the present invention is not limited to such examples. These peroxide radical polymerization initiators may be used alone or in combination of two or more.

  In the case where it is not necessary to use a polymerization initiator, it is preferable not to use a polymerization initiator substantially from the viewpoint of avoiding an adverse effect due to the polymerization initiator, and it is more preferable not to use a polymerization initiator at all. . Here, “substantially not use” means an amount of the polymerization initiator that does not substantially affect the polymerization reaction by the polymerization initiator. More specifically, the amount of the polymerization initiator per 1 mol of the catalyst is preferably 10 mmol or less, more preferably 1 mmol or less, and still more preferably 0.1 mmol or less.

  The amount of the polymerization initiator per 100 moles of all monomer components is preferably 0.005 to 30 moles, more preferably 0.00 from the viewpoint of increasing the polymerization rate and reducing the residual amount of unreacted monomers. It is 01-20 mol, More preferably, it is 0.02-15 mol.

  The amount of the polymerization initiator per liter of the reaction solution is 0.1 mmol or more, more preferably 0.5 mmol or more, further preferably 1 mmol or more, preferably 500 mmol or less, more preferably 100 mmol. Hereinafter, it is more preferably 50 mmol or less, and still more preferably 10 mmol or less.

  Furthermore, the amount of the polymerization initiator per 100 parts by mass of the radically polymerizable monomer may be appropriately set according to the desired physical properties of the polymer to be obtained, but is usually preferably 0.001 to 20 parts by mass. More preferably, it is 0.005-10 mass parts.

  The polymerization conditions for polymerizing the radical polymerizable monomer may be appropriately set according to the polymerization method of the radical polymerizable monomer, and are not particularly limited. The polymerization temperature is preferably room temperature to 200 ° C, more preferably 30 to 140 ° C. Moreover, it is preferable that the atmosphere at the time of polymerizing a radically polymerizable monomer is inert gas, such as nitrogen gas and argon gas. What is necessary is just to set reaction time suitably so that the polymerization reaction of a radically polymerizable monomer may be completed.

  As described above, according to Method X, a polymer having a functional group at at least one molecular end can be obtained.

  In the method Y, (A2) an organic iodine compound and (B) a compound that generates a radical as a catalyst and extracts iodine from the organic iodine compound, or coordinates with iodine of the organic iodine compound and is converted into iodine from the organic iodine compound. Characterized in that it comprises a step of living radical polymerization of a radically polymerizable monomer in the presence of a compound that abstracts and a step of introducing a functional group into at least one molecular terminal of the obtained polymer.

As a specific example of the method Y, for example,
(1) (A2) A method in which a radical polymerizable monomer is living radically polymerized in the presence of an organic iodine compound and (B) a catalyst, and the resulting polymer is reacted with a functional group-containing compound;
(2) Living radical polymerization of a radically polymerizable monomer in the presence of (A2) an organic iodine compound, which is a reaction product obtained by reacting iodine with an azo compound as an organic iodine compound, and (B) a catalyst However, the present invention is not limited to such examples.

  Examples of the radical polymerizable monomer used in Method Y include those similar to those used in Method X.

  Examples of the solvent, the (B) catalyst and the polymerization initiator used in the step of polymerizing the radical polymerizable monomer in Method Y are the same as those used in Method X. The polymerization conditions for polymerizing the radical polymerizable monomer by Method Y are preferably the same as those in Method X.

  The organic iodine compound (A2) used in the step of polymerizing the radical polymerizable monomer in the method Y is not particularly limited, and can be appropriately selected from organic iodine compounds that can be generally used. Examples of the organic iodine compound include iodotrichloromethane, dichlorodiiodomethane, iodotribromomethane, dibromodiiodomethane, bromotriiodomethane, iodoform, diiodomethane, methyl iodide, triiodoethane, ethyl iodide, and diiodo. Propane, isopropyl iodide, tert-butyl iodide, iododichloroethane, chlorodiiodoethane, chloroiodobropan, iododibromoethane, bromoiodopropane, 2-iodo-2-polyethyleneglycosylpropane, 2-iodo-2-amidino Propane, 2-iodo-2-cyanobutane, 2-iodo-2-cyano-4-methylpentane, 2-iodo-2-cyano-4-methyl-4-methoxypentane, 4-iodo-4-cyano-pentanoic acid, Methyl-2-io Isobutyrate, 2-iodo-2-methylpropanamide, 2-iodo-2,4-dimethylpentane, 2-iodo-2-methylpropionitrile, ethyl 2-iodo-2-phenylacetate, 2,5-diiodo Diethyl adipate, 1,4-bis (1′-iodoethyl) benzene, tris (2-iodoisobutyric acid) glycerol, 1,3,5-tris (1′-iodoethyl) benzene, 2-iodo-2-cyanobutanol, 4-methylpentane, cyano-4-methylpentane, 2-iodo-2-methyl-N- (2-hydroxyethyl) propionamide 4-methylpentane, 2-iodo-2-methyl-N- (1,1- Bis (hydroxymethyl) -2-hydroxyethyl) propionamide 4-methylpentane, 2-iodo-2- (2-imidazole) -2-yl) propane, 2-iodo-2- (2- (5-methyl-2-imidazolin-2-yl) propane, ethyl 2-iodopropanoate, ethyl 2-iodoisobutyrate, 2-iodoisobutyric acid, 2 -Iodo-2-phenylacetic acid, 2-hydroxyethyl-2-iodoisobutyrate, 2-hydroxyethyl-2-iodo-2-phenylacetate, iodoacetic acid, 2-iodopropanoic acid, 2-iodopropanamide, etc. Examples include alkyl iodides, but the present invention is not limited to such examples, and these organic iodine compounds may be used alone or in combination of two or more.

  In addition, in (A2) organic iodine compound, what corresponds to the organic iodine compound which has the said (A1) functional group is contained. (A2) When an organic iodine compound having a functional group (A1) is used as the organic iodine compound, (A1) an organic iodine compound having a functional group, and (B) a radical is generated as a catalyst from the organic iodine compound. A step of living radical polymerization of a radical polymerizable monomer in the presence of a compound that extracts iodine, or a compound that coordinates to iodine of the organic iodine compound and extracts iodine from the organic iodine compound, and the resulting polymer A polymer having functional groups at both molecular ends can be obtained by introducing a functional group into at least one of the molecular ends.

  The organic iodine compound can also be used as an organic iodine compound in this polymerization method by charging its raw materials and generating the organic iodine compound in situ during polymerization, that is, in a reaction solution. For example, an azo compound and iodine can be charged as raw materials, and an organic iodine compound can be generated in situ during the polymerization by the reaction between the two, which can be used as the organic iodine compound in this polymerization method. That is, the production method of the present invention may include a step of reacting iodine with an azo compound to produce an organic iodine compound.

  The azo compound used for generating the organic iodine compound is not particularly limited as long as it is a compound having an azo group. For example, the same as those exemplified as the azo radical polymerization initiator and the azo compound having the functional group. Preferred examples of the compound are: The azo compounds used for producing the organic iodine compound may be used alone or in combination of two or more.

  The amount of the azo compound used for generating the organic iodine compound is preferably 1 mol or more, more preferably 1.3 mol or more, relative to 1 mol of iodine because the production of the organic iodine compound is efficient. Further, in consideration of the fact that after the formation of the organic iodine compound, the unreacted azo compound acts as a radical polymerization initiator, the amount is preferably 5 mol or less, more preferably 3 mol or less, relative to 1 mol of iodine.

  The amount of the organic iodine compound per 100 mol of the radical polymerizable monomer is preferably 0.1 mol or more, more preferably 0.5 mol or more from the viewpoint of polymerization control, and 50 mol from the viewpoint of the degree of polymerization. The following is preferable, 40 mol or less is more preferable, and 10 mol or less is further more preferable.

  Further, the amount of the organic iodine compound per 100 parts by mass of the radical polymerizable monomer may be appropriately set according to the desired physical properties of the polymer to be obtained, but is usually preferably 0.001 to 20 parts by mass. More preferably, it is 0.005-10 mass parts.

  When the organic iodine compound is generated in-situ without being isolated, the amount of the organic iodine compound can be calculated from the amount of iodine used.

  As described above, (A2) the organic iodine compound of Method Y, (B) a compound that generates radicals as a catalyst and extracts iodine from the organic iodine compound, or coordinates with iodine of the organic iodine compound to form the organic A polymer can be obtained by a step of living radical polymerization of a radically polymerizable monomer in the presence of a compound that extracts iodine from an iodine compound.

  Examples of the step of introducing a functional group into at least one molecular terminal of the polymer obtained by Method Y include a method of reacting the obtained polymer with a functional group-containing compound. Specifically, for example, the polymer, the functional group-containing compound, the solvent, and, if necessary, a method of mixing an acid, a base, or the like as a catalyst can be mentioned, but the present invention is limited to such illustration only. It is not a thing. The order of mixing these components is arbitrary, and for example, these components may be mixed together. As a solvent, the thing similar to the solvent used when superposing | polymerizing the said radically polymerizable monomer can be illustrated.

  Examples of the functional group-containing compound include a compound containing at least one functional group and a reactive group that reacts with at least one molecular end of the polymer. Examples of the functional group include the same groups as the functional group introduced into at least one molecular end of the polymer. Examples of the reactive group include the same groups as the functional group. That is, examples of the functional group-containing compound include compounds having at least two functional groups, but they may be the same type of group or different types of groups. The functional group-containing compound preferably has 2 to 3 functional groups per molecule, and more preferably has 2 functional groups.

  Examples of the functional group-containing compound include amine compounds such as ethylenediamine and propyldiamine, dithiol compounds such as ethanedithiol, propanedithiol, octanedithiol, and hexadecanedithiol, allyl mercaptan, cysteine, cysteamine, mercaptoethanol, thioglycerol, Examples include thioglycolic acid, mercaptopropionic acid, 2-mercaptopropionic acid, 3-mercaptopropionic acid, thioacetic acid, thiomalic acid, 2-mercaptoethanesulfonic acid, and thiol compounds such as sodium salt and potassium salt thereof. The present invention is not limited to such examples. These functional group-containing compounds may be used alone or in combination of two or more.

  The amount of the functional group-containing compound may be appropriately set according to the type of radical polymerizable monomer, the polymerization conditions such as the polymerization temperature, the molecular weight of the target polymer, etc., and is not particularly limited, but the number average molecular weight is When obtaining several thousand to several tens of thousands of polymers, it is preferably 0.1 to 20 parts by mass and more preferably 0.5 to 15 parts by mass per 100 parts by mass of the radical polymerizable monomer. preferable.

  The conditions for introducing a functional group into at least one molecular terminal of the obtained polymer may be appropriately set according to the obtained polymer, functional group-introducing compound and the like, and are not particularly limited. The temperature at the time of introducing the functional group is preferably room temperature to 200 ° C, more preferably 30 to 150 ° C. Moreover, it is preferable that the atmosphere at the time of functional group introduction | transduction is inert gas, such as nitrogen gas and argon gas. The reaction time at the time of introducing the functional group may be appropriately set so that the reaction for introducing the functional group into at least one molecular end of the obtained polymer is completed, and is not particularly limited, but preferably 1 ~ 15 hours.

  As described above, according to Method Y, a polymer having a functional group at at least one molecular end can be obtained.

  The method for producing a polymer having a functional group at at least one molecular terminal may further include other steps as necessary. Examples of other processes include a purification process, a washing process, a catalyst deactivation process, a concentration process, a drying process, and a dilution process, but the present invention is not limited to such examples.

  The polymer obtained as described above has a functional group at its terminal. The functional group may be present only at one end of the polymer, or may be present at both ends.

  The content of iodine in the polymer having a functional group at at least one molecular terminal is 0.01 ppm or more from the viewpoint of improving antibacterial properties, and 5000 ppm or less, preferably from the viewpoint of improving safety to the human body and the environment. Is 3000 ppm or less, more preferably 1000 ppm or less, and still more preferably 100 ppm or less. In addition, the content rate of iodine is a value when measured based on the method described in the following examples.

  The content of heavy metals in the polymer having a functional group at at least one molecular end is 1 ppm or less, preferably 0.01 ppm or less, from the viewpoint of improving safety to the human body and the environment, and the lower limit is 0 ppm. . Examples of the heavy metal include cobalt, manganese, chromium, molybdenum, tungsten, copper, silver, gold, lead, platinum, iridium, osmium, palladium, rhodium, and ruthenium. In addition, the content rate of a heavy metal is a value when it measures based on the method as described in a following example.

  The number average molecular weight of the polymer having a functional group at at least one molecular end is 1000 or more, preferably 2000 or more, more preferably 3000 or more, from the viewpoint of improving safety to human body and environment and hemolysis resistance. From the viewpoint of improving release to the outside of the body, it is 90000 or less, preferably 50000 or less, more preferably 30000 or less, and further preferably 25000 or less.

In addition, the number average molecular weight of a polymer is a value when it measures on the following measuring conditions by gel permeation chromatography.
[Measurement conditions for number average molecular weight of polymer]
Measuring instrument: manufactured by Tosoh Corporation, product number: HLC-8320GPC
・ Molecular weight column: Tosoh Co., Ltd., product number: TSKgel G4000HHR connected in series ・ Eluent: dimethylformamide ・ Standard material for calibration curve: polyethylene glycol ・ Preparation of measurement solution: heavy to eluent (dimethylformamide) The combined solution is dissolved to prepare a solution having a polymer concentration of 0.3% by mass, and the filtrate after filtering the solution through a filter is used.

  The molecular weight distribution ([weight average molecular weight / number average molecular weight]) of the polymer having a functional group at at least one molecular end is preferably 1 to 2 from the viewpoint of improving safety to human body and environment and hemolysis resistance. Preferably it is 1-1.5, More preferably, it is 1-1.3.

  A polymer having a functional group at at least one molecular end can be used as particles. The average particle diameter of the particles is preferably 10 nm or more, more preferably 20 nm or more, from the viewpoint of preventing normal particles from acting on normal cells, and from the viewpoint of acting on lesion cells, preferably 1000 nm or less, more preferably 500 nm or less. More preferably, it is 200 nm or less.

  A polymer having a functional group at at least one molecular end has a functional group at at least one molecular end obtained by bonding polymers having a functional group at at least one molecular end of the same type or different types. It may be a block copolymer.

The polymer having a functional group at at least one molecular end preferably has a “structural unit derived from a biocompatible monomer”. The “structural unit derived from a biocompatible monomer” is a structural unit having a structure formed by polymerizing a biocompatible monomer, for example, carbon carbon contained in the biocompatible monomer. At least one of the double bonds is a structural unit having a structure in which a carbon-carbon single bond is replaced. Specifically, structural units derived from _{CH 2 = CHCOOCH 2 CH 2 OCH} 3 ( methoxy ethyl acrylate) _{is, -CH 2 -CH (COOCH 2 CH} 2 OCH 3) -, in a structural unit represented. The “structural unit derived from the biocompatible monomer” may be a structural unit having a structure formed by polymerizing the biocompatible monomer, and the biocompatible monomer is actually polymerized. It may be formed by a method other than that.

  A polymer having a functional group at at least one molecular end is a “structural unit derived from a monomer” (“derived from a biocompatible monomer” from the viewpoint of improving safety to human body and environment and hemolysis resistance. It is preferable that 50 mol or more of “structural unit derived from a biocompatible monomer” and “structural unit derived from a monomer other than the biocompatible monomer”) per 100 mol. More preferably, it contains more than 90 moles, more preferably more than 90 moles, more preferably 100 moles, that is, a polymer having a functional group at at least one molecular end having only “structural units derived from biocompatible monomers”. Coalescence is even more preferred. In addition, the polymer having a functional group at at least one molecular end containing 30 mol or more of “structural unit derived from biocompatible monomer” per 100 mol of “structural unit derived from monomer” It can be preferably used as a compatible medical polymer.

  For the polymer having a functional group at at least one molecular terminal, a radical polymerizable monomer containing 30 mol% or more of a biocompatible monomer with respect to 100 mol% of the radical polymerizable monomer is used as a raw material. In this case, it can be preferably used as a biocompatible polymer because it exhibits good biocompatibility. In addition, a polymer having a functional group at at least one molecular end can be preferably used as a medical polymer, and among such medical polymers, it can be more preferably used as a biocompatible medical polymer. .

  If necessary, the functional group of the biocompatible medical polymer may be modified with proteins, monosaccharides, polysaccharides, sugar chains, antibodies, nucleic acids, drug substances, and the like. These proteins, monosaccharides, polysaccharides, sugar chains, antibodies, nucleic acids, drug substances and the like may be directly bonded to the functional group of the biocompatible medical polymer or may be bonded via a linker. Good.

  In the resin composition of the present invention, the amount of iodine is 0.01 to 5000 ppm based on the mass of the polymer having a functional group at at least one molecular end, and the amount of heavy metal in the resin composition is that of the polymer. Since it is 1 ppm or less with respect to mass, there is little toxicity to a human body and influence on the environment, it is excellent in safety to the human body and the environment, and excellent in hemolysis resistance.

  In addition, the resin composition of this invention may contain the compound, additive, etc. derived from a raw material in the range which does not inhibit the objective of this invention, for example. Examples of the raw material-derived compound include residual monomers, polymerization initiator residues, polymerization catalyst residues such as iodine compounds, and the like. Examples of additives include water, physiological saline, pharmaceutically acceptable organic solvents, collagen, polyvinyl alcohol, polyvinylpyrrolidone, carboxyvinyl polymer, carboxymethylcellulose sodium salt, sodium polyacrylate, sodium alginate, water-soluble dextran. , Sodium carboxymethyl starch, pectin, methylcellulose, ethylcellulose, xanthan gum, gum arabic, casein, gelatin, agar, diglycerin, propylene glycol, polyethylene glycol, petroleum jelly, paraffin, stearyl alcohol, stearic acid, human serum albumin, mannitol, sorbitol, Lactose, phosphate buffered saline, biodegradable polymer, serum-free medium, surfactants acceptable as pharmaceutical additives Although such a physiological pH buffer acceptable in a living body and the like, and the present invention is not limited only to those exemplified. These additives may be used alone or in combination of two or more.

  The resin composition of the present invention contains a polymer having a functional group at at least one molecular end as an essential component. The amount of the polymer having a functional group at at least one molecular terminal per 100 parts by mass of the resin composition of the present invention is preferably 10 parts by mass or more, more preferably 20 parts by mass or more, and further preferably 30 parts by mass or more. Yes, preferably 99.99 parts by mass or less. When the resin composition contains a volatile component, the content of impurities such as the compound derived from the raw material may be in the above range with respect to 100 parts by mass of the resin composition, but the nonvolatile content in the resin composition is 100 masses. It is preferable that it is content with respect to a part.

  The non-volatile content in the resin composition of the present invention is not particularly limited, but is usually preferably 20 to 100% by mass, more preferably 50 to 100% by mass, from the viewpoint of improving handleability. More preferably, it is 70-100 mass%.

The nonvolatile content in the resin composition of the present invention is obtained by weighing 0.5 g of the resin composition and drying it with a hot air dryer at a temperature of 150 ° C. for 30 minutes.
[Nonvolatile content in resin composition (mass%)]
= ([Mass of residue] / [Mass of resin composition (0.5 g)]) × 100
Means the value obtained based on

  In the resin composition of the present invention, the amount of iodine is 0.01 ppm or more with respect to the mass of the polymer having a functional group at at least one molecular end, from the viewpoint of improving antibacterial properties, and with respect to the human body and the environment. From the viewpoint of improving safety, it is 5000 ppm or less, preferably 3000 ppm or less, more preferably 1000 ppm or less, and still more preferably 100 ppm or less. The amount of iodine is a value when measured based on the method described in the following examples. Moreover, it is preferable that the quantity of the iodine in the resin composition of this invention is the said range with respect to the mass of the non volatile matter in the resin composition of this invention from a viewpoint of simple quality control.

  The amount of heavy metal in the resin composition of the present invention is 1 ppm or less, preferably 0.01 ppm, based on the mass of the polymer having a functional group at at least one molecular end, from the viewpoint of improving safety to the human body and the environment. The lower limit is 0 ppm. In addition, the thing similar to the above can be illustrated as a heavy metal. The amount of heavy metal is a value when measured based on the method described in the following Examples. Moreover, it is preferable that the quantity of the heavy metal in the resin composition of this invention is the said range with respect to the mass of the non volatile matter in the resin composition of this invention from a viewpoint of simple quality control.

  The resin composition of the present invention contains at least 30 mol% of a biocompatible medical polymer having a functional group at at least one molecular terminal with respect to 100 mol% of the polymer having a functional group at at least one molecular terminal. In this case, since it exhibits good biocompatibility, it can be preferably used as a biocompatible resin composition. In addition, the resin composition of the present invention can be preferably used as a medical resin composition, and more preferably can be used as a biocompatible medical resin composition among the medical resin compositions.

  From the viewpoint of improving the biocompatibility of the obtained medical resin composition, the content of the biocompatible medical polymer having a functional group at at least one molecular end contained in the medical resin composition of the present invention is as follows. Preferably, it is at least 30 mol%, more preferably at least 50 mol%, even more preferably at least 80 mol%, even more preferably at least 90 mol%, based on 100 mol% of the polymer having a functional group at at least one molecular end. Still more preferably, it is 100 mol%.

  The medical resin composition of the present invention can be used, for example, as a biocompatible medical material such as a carrier for holding a drug or the like. Examples of a method for retaining a drug or the like with the medical resin composition of the present invention include, for example, bonding a drug or the like to the functional group of the biocompatible medical polymer used in the medical resin composition of the present invention. A method of combining a carrier and a drug, etc., a method of mixing a medical resin composition and a drug so as to have a uniform composition, a method of coating particles of a drug or the like with a medical resin composition, a lipid A method of making a mixture of a drug and a medical resin composition into particles and encapsulating a drug or the like inside the resulting particle, and coating a particle encapsulating a drug or the like with a liposome with a medical resin composition A method of encapsulating the particles inside the outer skin of the resin composition, and coating the particles of a mixture of drugs and liposomes with the medical resin composition, so that the particles are put inside the outer skin of the medical resin composition Method for packaging, by micellar drug and medical resin composition, although a method for encapsulating drugs and the like, the present invention is not limited only to those exemplified.

  The liposome is, for example, a method in which lipid is dissolved in a solvent such as tert-butyl alcohol and then freeze-dried, or a solution in which a drug is dissolved is added to the lipid to swell the lipid and disperse with ultrasound. Thereafter, it can be prepared by a method of adding polyethylene glycol-phosphatidylethanolamine or the like to the obtained dispersion.

  The liposome is preferably cationized with a cationizing agent. As the liposome, for example, hydrogenated soybean lecithin, cholesterol, 3,5-dipentadecyloxybenzamidine hydrochloride and the like are dissolved in a solvent such as tert-butyl alcohol, and the obtained lipid mixed solution is frozen. be able to. Lipids constituting liposomes are stable in vivo. Examples of the lipid include lipids derived from biomaterials, phospholipids or derivatives thereof, lipids other than phospholipids or derivatives thereof, and the like. Examples of the phospholipid include phospholipids such as phosphatidylcholine (lecithin), phosphatidylethanolamine, phosphatidylserine, phosphatidylinositol, sphingomyelin, cardioribine, and the phospholipids added with hydrogen.

  In the above examples, liposomes are used. Instead of liposomes, for example, emulsions, nanoparticles, microparticles, polymer compounds and the like can be used.

  A biologically or pharmacologically active drug can be used as the drug. Examples of the drug include an antitumor agent, an anticancer agent, an antibiotic, an antiviral agent, an anticancer effect enhancing agent, an immune enhancing agent, an immunomodulating agent, an immune recovery agent, a radiosensitizer, a radioprotectant, an antihistamine, and an anti-inflammatory Agent, decongestant, antifungal agent, anti-arthritic agent, anti-asthma agent, angiogenesis inhibitor, enzyme agent, antioxidant, hormone, angiotensin converting enzyme inhibitor, smooth muscle cell proliferator, smooth muscle cell migration Inhibitor, platelet aggregation inhibitor, chemical mediator release inhibitor, vascular endothelial cell growth promoter, vascular endothelial cell growth inhibitor, interferon, interleukin, colony stimulating factor, cytokine, tumor necrosis factor, granulocyte macrophage colony Stimulating factor, granulocyte colony stimulating factor, macrophage colony stimulating factor, stem cell factor, β-type transforming growth factor, liver Cell growth factor, vascular endothelial growth factor, erythropoietin, vaccine, protein, mucoprotein, peptide, polysaccharide, lipopolysaccharide, sugar chain, antisense, ribozyme, decoy, nucleic acid, antibody, etc. However, the present invention is not limited to such examples. These drugs may be used alone or in combination of two or more.

  Although the medical resin composition is obtained as described above, the biocompatible medical polymer used in the medical resin composition may be crosslinked. Examples of the method for crosslinking the polymer include a chemical crosslinking method and a physical crosslinking method. Chemical crosslinking methods include, for example, epoxy compounds, oxidized starch, glutaraldehyde, formaldehyde, dimethyl suberiminate, carbodiimide, succinimidyl compounds, diisocyanate compounds, acyl azides, reuterin, tris (hydroxymethyl) phosphine, copper ascorbate, glucose There is a method of cross-linking a polymer using a chemical cross-linking agent such as lysine and a photo-oxidizing agent, a method of chemically cross-linking a polymer by thermal dehydration, ultraviolet irradiation, electron beam irradiation, gamma ray irradiation, etc. Can be mentioned. Examples of the physical crosslinking method include a method of crosslinking a polymer with a salt, a method of crosslinking a polymer by electrostatic interaction, a method of crosslinking a polymer by hydrogen bonding, and a polymer by hydrophobic interaction. And the like. As the crosslinking method, only one type may be used, or two or more types may be used in combination.

  Examples of subjects to which the drug is administered include mammals such as humans, monkeys, mice, and livestock, but the present invention is not limited to such examples.

  When the drug is administered by injection, the drug can be injected into the body by intravenous injection such as infusion, intramuscular injection, intraperitoneal injection, subcutaneous injection, intradermal injection, intratumoral injection, and the like.

  The amount of the drug to be retained in the medical resin composition of the present invention varies depending on the subject to which the drug is administered, the type of drug, etc., and thus cannot be determined unconditionally, but usually the medical resin composition of the present invention It is preferable that it is about 1 microgram-50g per 100g of polymers (solid content) contained in.

  As described above, the medical resin composition of the present invention has less toxicity to the human body and less environmental impact, is superior in safety to the human body and the environment, and is superior in hemolysis resistance. It is expected to be used as a biocompatible medical material such as a pharmaceutical carrier to be held and introduced into the body orally or via blood, for example, an injectable pharmaceutical carrier or an orally administered pharmaceutical carrier. The

  EXAMPLES Next, although this invention is demonstrated further in detail based on an Example, this invention is not limited only to this Example.

Example 1
In a 30 mL Schlenk tube, 4 g of methoxyethyl acrylate [manufactured by Nippon Shokubai Co., Ltd.], 0.08 g of iodine [manufactured by Wako Pure Chemical Industries, Ltd.], 4,4′-azobis (4-cyanopentanoic acid) (Sigma Aldrich) 0.27 g, 4 g of diglyme [Tokyo Chemical Industry Co., Ltd.] and 0.11 g of tetrabutylammonium iodide [Tokyo Chemical Industry Co., Ltd.] were added, and the inner space of the Schlenk tube was filled with argon gas. Replaced. After stirring the contents of the Schlenk tube at 115 ° C. for 2 hours, 2.0 g of butyl acetate was added into the Schlenk tube and stirred for 5 hours under reflux, and then alumina powder (manufactured by Sigma Aldrich, product number: 199974). 5 g was added to the Schlenk tube, stirred for 30 minutes, and then filtered through PTFE filter paper (pore diameter: 100 μm) to obtain a filtrate.

  By adding 1.5 g of activated carbon [Osaka Gas Chemical Co., Ltd., product number: Shirakaba A] to the filtrate obtained above, stirring for 30 minutes, and then filtering with PTFE filter paper (pore size: 100 μm) The obtained filtrate was freeze-dried to obtain a resin composition containing a polymer composed of polymethoxyethyl acrylate having a carboxyl group at one molecular end. The number average molecular weight of the obtained polymer was 5300, and the molecular weight distribution (weight average molecular weight / number average molecular weight, hereinafter referred to as Mw / Mn) was 1.2. Further, the nonvolatile content in the resin composition was 99.9% by mass or more. In addition, although the non volatile matter contained in the said resin composition contains a trace amount of iodine compounds, it is thought that it is substantially comprised with a polymer (same in a following example).

  Next, the safety of the human body and the environment and hemolysis resistance of the resin composition obtained above were examined based on the following methods. The results are shown in Table 1. In addition, in each physical property, those having at least one evaluation of x are rejected.

[Safety for human body and environment]
The resin composition obtained in Example 1 was dissolved in methyl ethyl ketone to prepare a solution having a resin composition concentration of 2.5% by mass. The obtained solution was measured with a fluorescent X-ray analyzer (manufactured by Philips, product number: PW2404), and the amount of iodine (ppm) and the amount of copper (ppm) in the resin composition obtained in Example 1 were determined. Safety for human body and environment was evaluated based on the following evaluation criteria.

(Evaluation criteria for the amount of iodine)
◎: The amount of iodine (ppm) is 100 ppm or less ○: The amount of iodine (ppm) exceeds 100 ppm and 1000 ppm or less Δ: The amount of iodine (ppm) exceeds 1000 ppm and 3000 ppm or less ΔΔ: The amount of iodine (ppm) Exceeds 3000 ppm, and is less than 5000 ppm x: iodine amount (ppm) exceeds 5000 ppm

(Evaluation criteria for copper content)
○: The amount of copper (ppm) is 0.01 ppm or less Δ: The amount of copper (ppm) exceeds 0.01 ppm and 1 ppm or less ×: The amount of copper (ppm) exceeds 1 ppm

[Hemolysis resistance]
The resin composition obtained in Example 1 was dissolved in ethyl acetate to prepare a solution having a resin composition concentration of 0.2 mg / mL. The resin solution obtained in Example 1 was coated by dispensing 3 mL of the obtained solution to a borosilicate glass microplate (outer diameter 18 mm well, 24 holes) and drying at 100 ° C. for 30 minutes. Got a well.

  ４８48 mL of phosphate buffered saline (Wako Pure Chemical Industries, Ltd., PBS buffer solution) was added to 2 mL of defibrillated blood (manufactured by Kojin Bio), and mixed by inverting in a 50 mL centrifuge tube at 4 ° C. And centrifuged at 2000 rpm for 10 minutes. A blood solution was obtained by adding 48 mL of PBS solution to the mixed solution from which the supernatant was removed, and mixing by inverting. 40 mL of phosphate buffered saline (manufactured by Wako Pure Chemical Industries, Ltd., PBS buffer solution) was added to 40 mL of the obtained blood solution and mixed by inversion to obtain a diluted blood solution.

  Next, 3 mL of the blood diluted solution was added to the well coated with the resin composition obtained in Example 1, and incubated at 37 ° C. for 1 hour or 4 hours. After collecting 250 μL of the solution after incubation for 1 hour or 4 hours, dispensing it into a polystyrene microplate (outer diameter 8 mm well, 96 holes), and centrifuging the microplate at 4 ° C. and 2000 rpm for 5 minutes Then, 150 μL of the supernatant was seeded on a new microplate, and the absorbance of the supernatant at a wavelength of 545 nm was measured with a microplate reader [Corona Electric Co., Ltd., product number: MTP-900Lab, the same applies hereinafter].

  2 mg / mL phosphate buffered saline [Wako Pure Chemical Industries, Ltd.] of polyoxyethylene (10) octylphenyl ether [trade name: Triton-X, manufactured by Wako Pure Chemical Industries, Ltd.] was added to 2 mL of the blood solution obtained above. (PBS Co., Ltd., PBS buffer solution) 2 mL of the solution was added, and 250 μL of the solution mixed by inversion was collected and dispensed into a polystyrene microplate (outer diameter 8 mm well, 96 holes), and the plate was adjusted to 2000 rpm at 4 ° C. After centrifugation for 5 minutes, 150 μL of the supernatant was seeded on a new microplate, and the absorbance of the supernatant at a wavelength of 545 nm was measured with a microplate reader.

From the absorbance measured above, the hemolysis degree (%) is expressed by the formula:
[Hemolysis degree (%)] = ([Absorbance of supernatant after incubation] ÷ [Absorbance when using Triton-X]) × 100
The hemolysis resistance was evaluated based on the following evaluation criteria.
(Evaluation criteria)
◎: Hemolysis is less than 10% ○: Hemolysis is 10% or more and less than 25% Δ: Hemolysis is 25% or more and less than 50% ×: Hemolysis is 50% or more

Example 2
In a 30 mL Schlenk tube, 4 g of methoxyethyl acrylate [manufactured by Nippon Shokubai Co., Ltd.], 0.12 g of 2-iodo-2-methylpropionitrile [manufactured by Tokyo Chemical Industry Co., Ltd.] and tetrabutylammonium iodide [Tokyo Kasei] [Industry Co., Ltd.] After adding 0.11 g, the internal space of the Schlenk tube was replaced with argon gas. After the contents of the Schlenk tube were stirred at 115 ° C. for 24 hours, 1.5 g of alumina powder (manufactured by Sigma Aldrich, product number: 199974) was added to the Schlenk tube, stirred for 30 minutes, and then filtered with PTFE filter paper (fine The filtrate was obtained by filtering through a pore size of 100 μm.

  By adding 1.5 g of activated carbon [Osaka Gas Chemical Co., Ltd., product number: Shirakaba A] to the filtrate obtained above, stirring for 30 minutes, and then filtering with PTFE filter paper (pore size: 100 μm) The obtained filtrate was freeze-dried to obtain a polymer.

  Next, 0.24 g of ethylenediamine (manufactured by Wako Pure Chemical Industries, Ltd.), 1.5 g of n-butanol and 1.5 g of diglyme are added to 2 g of the polymer obtained above and stirred at 110 ° C. for 8 hours. As a result, a reaction solution was obtained. A polymer comprising polymethoxyethyl acrylate having an amino group at one molecular end is obtained by adding 10 g of deionized water to the resulting reaction solution, removing unreacted ethylenediamine by liquid separation, and then freeze-drying. A resin composition containing was obtained. The number average molecular weight of the obtained polymer was 5200, and the molecular weight distribution (Mw / Mn) was 1.3. Further, the nonvolatile content in the resin composition was 99.9% by mass or more.

  Next, the safety of the human body and the environment and hemolysis resistance of the resin composition obtained above were examined in the same manner as in Example 1. The results are shown in Table 1.

Example 3
In a 30 mL Schlenk tube, 4 g of methoxyethyl acrylate (manufactured by Nippon Shokubai Co., Ltd.), 0.064 g of iodine (manufactured by Wako Pure Chemical Industries, Ltd.), 2,2′-azobis (2,4-dimethylvaleronitrile) 0 0.082 g and 1.0 g of tetrabutylammonium iodide [Tokyo Chemical Industry Co., Ltd.] were added, and the internal space of the Schlenk tube was replaced with argon gas. After the contents of the Schlenk tube were stirred at 115 ° C. for 24 hours, 1.5 g of alumina powder (manufactured by Sigma Aldrich, product number: 199974) was added to the Schlenk tube, stirred for 30 minutes, and then filtered with PTFE filter paper (fine The filtrate was obtained by filtering through a pore size of 100 μm.

  By adding 1.5 g of activated carbon [Osaka Gas Chemical Co., Ltd., product number: Shirakaba A] to the filtrate obtained above, stirring for 30 minutes, and then filtering with PTFE filter paper (pore size: 100 μm) The obtained filtrate was freeze-dried to obtain a polymer.

  Next, 0.36 g of cysteamine [manufactured by Wako Pure Chemical Industries, Ltd.], 1.5 g of n-butanol and 1.5 g of diglyme are added to 2 g of the polymer obtained above, and the mixture is stirred at 110 ° C. for 8 hours. As a result, a reaction solution was obtained. A polymer composed of polymethoxyethyl acrylate having a thiol group at one molecular end is obtained by adding 10 g of deionized water to the resulting reaction solution, removing unreacted cysteamine by liquid separation, and then freeze-drying. A resin composition containing was obtained. The number average molecular weight of the obtained polymer was 4800, and the molecular weight distribution (Mw / Mn) was 1.3. Further, the nonvolatile content in the resin composition was 99.9% by mass or more.

  Next, the safety of the human body and the environment and hemolysis resistance of the resin composition obtained above were examined in the same manner as in Example 1. The results are shown in Table 1.

Example 4
In a 30 mL Schlenk tube, 4-hydroxyethyl methacrylate [manufactured by Nippon Shokubai Co., Ltd.] 4 g, iodine [manufactured by Wako Pure Chemical Industries, Ltd.] 0.08 g, 4,4′-azobis (4-cyanopentanoic acid) ( After adding 0.27 g of Sigma Aldrich Co., Ltd., 4 g of diglyme [manufactured by Tokyo Chemical Industry Co., Ltd.] and 0.11 g of tetrabutylammonium iodide [manufactured by Tokyo Chemical Industry Co., Ltd.], the internal space of the Schlenk tube was replaced with argon. Replaced with gas. The contents of the Schlenk tube were stirred at 80 ° C. for 4 hours, and then stirred for 5 hours with the temperature raised to 100 ° C., and then 1.5 g of alumina powder (manufactured by Sigma Aldrich, product number: 199974) was placed in the Schlenk tube. After adding and stirring for 30 minutes, the filtrate was obtained by filtering with PTFE filter paper (pore diameter: 100 μm).

  By adding 1.5 g of activated carbon [Osaka Gas Chemical Co., Ltd., product number: Shirakaba A] to the filtrate obtained above, stirring for 30 minutes, and then filtering with PTFE filter paper (pore size: 100 μm) The obtained filtrate was freeze-dried to obtain a resin composition containing a polymer composed of polyhydroxyethyl methacrylate having a carboxyl group at one molecular end. The number average molecular weight of the obtained polymer was 7000, and the molecular weight distribution (Mw / Mn) was 1.2. Further, the nonvolatile content in the resin composition was 99.9% by mass or more.

  Next, the safety of the resin composition obtained above with respect to the human body and the environment was examined in the same manner as in Example 1. The results are shown in Table 1.

  The resin composition obtained in Example 4 was dissolved in isopropyl alcohol to prepare a solution having a resin composition concentration of 0.2 mg / mL. 3 ml of the prepared solution was dispensed into a borosilicate glass microplate (outer diameter 18 mm well, 24 holes), and then dried at 110 ° C. for 30 minutes, whereby the resin composition obtained in Example 4 was coated. Well got. In Example 1, instead of the well coated with the resin composition obtained in Example 1, the well coated with the resin composition obtained in Example 4 was used. Similarly, hemolysis resistance was examined. The results are shown in Table 1.

Example 5
In a 30 mL Schlenk tube, 4 g of 2-hydroxyethyl methacrylate (manufactured by Nippon Shokubai Co., Ltd.), 0.090 g of 2-iodoisobutyric acid (manufactured by Joint Resources Co., Ltd.), 4 g of diglyme (manufactured by Tokyo Chemical Industry Co., Ltd.) and tetra After adding 0.15 g of butylammonium iodide [manufactured by Tokyo Chemical Industry Co., Ltd.], the internal space of the Schlenk tube was replaced with argon gas. The contents of the Schlenk tube were stirred for 5 hours at 80 ° C., and then stirred for 5 hours with the temperature raised to 100 ° C., and then 1.5 g of alumina powder (manufactured by Sigma Aldrich, product number: 199974) was placed in the Schlenk tube. After adding and stirring for 30 minutes, the filtrate was obtained by filtering with PTFE filter paper (pore diameter: 100 μm).

  By adding 1.5 g of activated carbon [Osaka Gas Chemical Co., Ltd., product number: Shirakaba A] to the filtrate obtained above, stirring for 30 minutes, and then filtering with PTFE filter paper (pore size: 100 μm) The obtained filtrate was freeze-dried to obtain a resin composition containing a polymer composed of polyhydroxyethyl methacrylate having a carboxyl group at one molecular end. The number average molecular weight of the obtained polymer was 5500, and the molecular weight distribution (Mw / Mn) was 1.4. Further, the nonvolatile content in the resin composition was 99.9% by mass or more.

  Next, the safety of the human body and the environment and hemolysis resistance of the resin composition obtained above were examined in the same manner as in Example 4. The results are shown in Table 1.

Example 6
In a 30 mL Schlenk tube, 4-hydroxyethyl methacrylate [manufactured by Nippon Shokubai Co., Ltd.] 4 g, 2-iodo-2-methylpropionitrile [manufactured by Tokyo Chemical Industry Co., Ltd.] 0.12 g, tetrabutylammonium iodide [ After 0.11 g of Tokyo Chemical Industry Co., Ltd.] and 2.0 g of diglyme [Tokyo Chemical Industry Co., Ltd.] were added, the internal space of the Schlenk tube was replaced with argon gas. After stirring the contents of the Schlenk tube at 50 ° C. for 6 hours, 1.5 g of alumina powder (manufactured by Sigma Aldrich, product number: 199974) was added to the Schlenk tube, stirred for 30 minutes, and then filtered with PTFE filter paper (fine The filtrate was obtained by filtering through a pore size of 100 μm.

  By adding 1.5 g of activated carbon [Osaka Gas Chemical Co., Ltd., product number: Shirakaba A] to the filtrate obtained above, stirring for 30 minutes, and then filtering with PTFE filter paper (pore size: 100 μm) The obtained filtrate was freeze-dried to obtain a polymer. By adding 0.24 g of ethylenediamine [manufactured by Wako Pure Chemical Industries, Ltd.], 1.5 g of n-butanol and 1.5 g of diglyme to 2 g of the obtained polymer, the reaction solution was stirred at 110 ° C. for 8 hours. Got. 10 g of deionized water is added to the obtained reaction solution, and unreacted ethylenediamine is removed by liquid separation and freeze-dried, thereby containing a polymer composed of polyhydroxyethyl methacrylate having an amino group at one molecular end. A resin composition was obtained. The number average molecular weight of the obtained polymer was 5300, and the molecular weight distribution (Mw / Mn) was 1.3. Further, the nonvolatile content in the resin composition was 99.9% by mass or more.

  Next, the safety of the human body and the environment and hemolysis resistance of the resin composition obtained above were examined in the same manner as in Example 4. The results are shown in Table 1.

Example 7
In a 30 mL Schlenk tube, 4 g of 2-hydroxyethyl methacrylate (manufactured by Nippon Shokubai Co., Ltd.), 0.064 g of iodine (manufactured by Wako Pure Chemical Industries, Ltd.), 2,2′-azobis (4-methoxy-2,4 -0.12 g of dimethylvaleronitrile), 2.0 g of diglyme [manufactured by Tokyo Chemical Industry Co., Ltd.] and 0.11 g of tetrabutylammonium iodide [manufactured by Tokyo Chemical Industry Co., Ltd.], and then the internal space of the Schlenk tube Was replaced with argon gas. After stirring the contents of the Schlenk tube at 60 ° C. for 5 hours, 1.5 g of alumina powder (manufactured by Sigma Aldrich, product number: 199974) was added to the Schlenk tube, stirred for 30 minutes, and then PTFE filter paper (fine The filtrate was obtained by filtering through a pore size of 100 μm.

  By adding 1.5 g of activated carbon [Osaka Gas Chemical Co., Ltd., product number: Shirakaba A] to the filtrate obtained above, stirring for 30 minutes, and then filtering with PTFE filter paper (pore size: 100 μm) The obtained filtrate was freeze-dried to obtain a polymer.

  Next, 0.36 g of cysteamine [manufactured by Wako Pure Chemical Industries, Ltd.], 1.5 g of n-butanol and 1.5 g of diglyme are added to 2.0 g of the polymer obtained above, and the mixture is heated at 110 ° C. for 8 hours. The reaction solution was obtained by stirring. 10 g of deionized water is added to the resulting reaction solution, and unreacted cysteamine is removed by liquid separation and freeze-dried, thereby containing a polymer composed of polyhydroxyethyl methacrylate having a thiol group at one molecular end. A resin composition was obtained. The number average molecular weight of the obtained polymer was 5000, and the molecular weight distribution (Mw / Mn) was 1.3. Further, the nonvolatile content in the resin composition was 99.9% by mass or more.

  Next, the safety of the human body and the environment and hemolysis resistance of the resin composition obtained above were examined in the same manner as in Example 4. The results are shown in Table 1.

Example 8
In a 30 mL Schlenk tube, 4 g of 2-hydroxyethyl methacrylate (manufactured by Nippon Shokubai Co., Ltd.), azobisisobutyronitrile (manufactured by Tokyo Chemical Industry Co., Ltd.) 0.10 g, iodosuccinimide (manufactured by Tokyo Chemical Industry Co., Ltd.) ] 0.01 g, iodine [manufactured by Wako Pure Chemical Industries, Ltd.] 0.079 g and diglyme [manufactured by Tokyo Chemical Industry Co., Ltd.] 2.0 g were added, and the internal space of the Schlenk tube was replaced with argon gas. After stirring the contents of the Schlenk tube at 60 ° C. for 5 hours, 1.5 g of alumina powder (manufactured by Sigma Aldrich, product number: 199974) was added to the Schlenk tube, stirred for 30 minutes, and then PTFE filter paper (fine The filtrate was obtained by filtering through a pore size of 100 μm.

  By adding 1.5 g of activated carbon [Osaka Gas Chemical Co., Ltd., product number: Shirakaba A] to the filtrate obtained above, stirring for 30 minutes, and then filtering with PTFE filter paper (pore size: 100 μm) The obtained filtrate was freeze-dried to obtain a polymer.

  Next, 0.24 g of ethylenediamine (manufactured by Wako Pure Chemical Industries, Ltd.), 1.5 g of n-butanol and 1.5 g of diglyme are added to 2.0 g of the polymer obtained above, and the mixture is heated at 110 ° C. for 8 hours. The reaction solution was obtained by stirring. 10 g of deionized water is added to the obtained reaction solution, and unreacted ethylenediamine is removed by liquid separation and freeze-dried, thereby containing a polymer composed of polyhydroxyethyl methacrylate having an amino group at one molecular end. A resin composition was obtained. The number average molecular weight of the obtained polymer was 4800, and the molecular weight distribution (Mw / Mn) was 1.2. Further, the nonvolatile content in the resin composition was 99.9% by mass or more.

  Next, the safety of the human body and the environment and hemolysis resistance of the resin composition obtained above were examined in the same manner as in Example 1. The results are shown in Table 1.

Example 9
In a 30 mL Schlenk tube, 4 g of methoxyethyl acrylate [manufactured by Nippon Shokubai Co., Ltd.], 0.08 g of iodine [manufactured by Wako Pure Chemical Industries, Ltd.], 4,4′-azobis (4-cyanopentanoic acid) (Sigma Aldrich) 0.27 g, 4 g of diglyme [Tokyo Chemical Industry Co., Ltd.] and 0.11 g of tetrabutylammonium iodide [Tokyo Chemical Industry Co., Ltd.] were added, and the inner space of the Schlenk tube was filled with argon gas. Replaced. After stirring the contents of the Schlenk tube at 115 ° C. for 2 hours, 2.0 g of butyl acetate was added into the Schlenk tube and stirred for 5 hours under reflux, and then alumina powder (manufactured by Sigma Aldrich, product number: 199974). 5 g was added to the Schlenk tube, stirred for 30 minutes, and then filtered through PTFE filter paper (pore diameter: 100 μm) to obtain a filtrate.

  By adding 1.5 g of activated carbon [Osaka Gas Chemical Co., Ltd., product number: Shirakaba A] to the filtrate obtained above, stirring for 30 minutes, and then filtering with PTFE filter paper (pore size: 100 μm) The obtained filtrate was freeze-dried to obtain a polymer.

  Next, 0.24 g of cysteamine [manufactured by Wako Pure Chemical Industries, Ltd.], 1.5 g of n-butanol and 1.5 g of diglyme are added to 2.0 g of the polymer obtained above, and the mixture is heated at 110 ° C. for 8 hours. The reaction solution was obtained by stirring. 10 g of deionized water is added to the resulting reaction solution, and unreacted cysteamine is removed by liquid separation and lyophilized to obtain a polycarboxylic acid having a carboxylic acid at one molecular end and a thiol group at the other molecular end. A resin composition containing a polymer composed of methoxyethyl acrylate was obtained. The number average molecular weight of the obtained polymer was 5700, and the molecular weight distribution (Mw / Mn) was 1.4. Further, the nonvolatile content in the resin composition was 99.9% by mass or more.

  Next, the safety of the human body and the environment and hemolysis resistance of the resin composition obtained above were examined in the same manner as in Example 1. The results are shown in Table 1.

Example 10
In a 30 mL Schlenk tube, 4 g of methoxyethyl acrylate [manufactured by Nippon Shokubai Co., Ltd.], 0.08 g of iodine [manufactured by Wako Pure Chemical Industries, Ltd.], 4,4′-azobis (4-cyanopentanoic acid) (Sigma Aldrich) 0.27 g, 4 g of diglyme [Tokyo Chemical Industry Co., Ltd.] and 0.11 g of tetrabutylammonium iodide [Tokyo Chemical Industry Co., Ltd.] were added, and the inner space of the Schlenk tube was filled with argon gas. Replaced. After stirring the contents of the Schlenk tube at 115 ° C. for 2 hours, 2.0 g of butyl acetate was added into the Schlenk tube and stirred for 5 hours under reflux, and then alumina powder (manufactured by Sigma Aldrich, product number: 199974). 5 g was added to the Schlenk tube, stirred for 30 minutes, and then filtered through PTFE filter paper (pore diameter: 100 μm) to obtain a filtrate.

  By adding 1.5 g of activated carbon [Osaka Gas Chemical Co., Ltd., product number: Shirakaba A] to the filtrate obtained above, stirring for 30 minutes, and then filtering with PTFE filter paper (pore size: 100 μm) The obtained filtrate was freeze-dried to obtain a polymer.

  Next, 0.24 g of aminoethanol (manufactured by Wako Pure Chemical Industries, Ltd.), 1.5 g of n-butanol and 1.5 g of diglyme were added to 2.0 g of the polymer obtained above, and the mixture was heated at 110 ° C. for 8 g. The reaction solution was obtained by stirring for a period of time. 10 g of deionized water is added to the resulting reaction solution, unreacted cysteamine is removed by liquid separation, and lyophilization is performed, so that a polycarboxylic acid having a carboxylic acid at one molecular end and a hydroxyl group at the other molecular end is obtained. A resin composition containing a polymer composed of methoxyethyl acrylate was obtained. The number average molecular weight of the obtained polymer was 5500, and the molecular weight distribution (Mw / Mn) was 1.4. Further, the nonvolatile content in the resin composition was 99.9% by mass or more.

  Next, the safety of the human body and the environment and hemolysis resistance of the resin composition obtained above were examined in the same manner as in Example 1. The results are shown in Table 1.

Comparative Example 1
After adding 200 mg of 4- (1-bromoethyl) benzoic acid, 5.2 g of methyl methacrylate and 5 g of n-butanol in a 30 mL Schlenk tube, the inner space of the Schlenk tube was replaced with nitrogen gas. Into the Schlenk tube, 400 mg of a bipyridine ligand and 147 mg of copper bromide were added and stirred at 80 ° C. for 3 hours to obtain a reaction solution. The resulting reaction solution was purified by passing through a 4 g alumina column, and then lyophilized to obtain a resin composition containing a polymer composed of polymethyl methacrylate having a carboxyl group at one molecular end. The number average molecular weight of the obtained polymer was 4900, and the molecular weight distribution (Mw / Mn) was 1.2. Further, the nonvolatile content in the resin composition was 99.9% by mass or more.

  Next, the safety of the human body and the environment and hemolysis resistance of the resin composition obtained above were examined in the same manner as in Example 1. The results are shown in Table 1.

  From the results shown in Table 1, it can be seen that each of the resin compositions obtained in each example is excellent in safety to human body and environment and excellent in hemolysis resistance.

Claims (6)

  A resin composition containing a polymer having a functional group at at least one molecular terminal and iodine, wherein the amount of the iodine is 0.01 to 5000 ppm with respect to the mass of the polymer, in the resin composition The resin composition, wherein the amount of heavy metal is 1 ppm or less with respect to the mass of the polymer.   A medical resin composition containing a polymer having a functional group at at least one molecular terminal and iodine, wherein the amount of iodine is 0.01 to 5000 ppm with respect to the mass of the polymer, The amount of heavy metals in a resin composition is 1 ppm or less with respect to the mass of the said polymer, The medical resin composition characterized by the above-mentioned.   A method for producing a polymer having a functional group at at least one molecular end, wherein (A1) an organic iodine compound having a functional group and (B) a radical is generated as a catalyst to extract iodine from the organic iodine compound. A functional group at at least one molecular end characterized by polymerizing a radical polymerizable monomer in the presence of a compound or a compound that coordinates to iodine of the organic iodine compound and extracts iodine from the organic iodine compound The manufacturing method of the polymer which has this.   A method for producing a polymer having a functional group at at least one molecular end, wherein (A2) an organic iodine compound, and (B) a compound that generates radicals as a catalyst to extract iodine from the organic iodine compound, or A step of polymerizing a radical polymerizable monomer in the presence of a compound that coordinates to iodine of the organic iodine compound and extracts iodine from the organic iodine compound, and a functional group at least one molecular end of the obtained polymer A method for producing a polymer having a functional group at at least one molecular end thereof.   A method for producing a biocompatible medical polymer having a functional group at at least one molecular end, wherein (A1) an organic iodine compound having a functional group and (B) a radical as a catalyst to generate the organic iodine A biocompatible radical polymerizable monomer is polymerized in the presence of a compound that extracts iodine from the compound or a compound that coordinates to iodine of the organic iodine compound and extracts iodine from the organic iodine compound. A method for producing a biocompatible medical polymer having a functional group at at least one molecular end.   A method for producing a biocompatible medical polymer having a functional group at at least one molecular end, wherein (A2) an organic iodine compound, and (B) a radical is generated as a catalyst to generate iodine from the organic iodine compound. A step of polymerizing a biocompatible radical polymerizable monomer in the presence of a compound to be extracted or a compound that coordinates to iodine of the organic iodine compound and extracts iodine from the organic iodine compound, and the obtained biocompatible property And a step of introducing a functional group into at least one molecular terminal of the medical polymer. A method for producing a biocompatible medical polymer having a functional group at at least one molecular terminal.