Method for producing antithrombotic coating material

Patent metadata

Field	Value
Publication number	US-2016263294-A1
Application number	US-201615066564-A
Country	US
Kind code	A1
Filing date	Mar 10, 2016
Priority date	Mar 10, 2015
Publication date	Sep 15, 2016
Grant date	—

Abstract

Provided is a method for producing an antithrombotic coating material in which a high molecular weight polymer can be obtained by a solution polymerization using a radical polymerization initiator. The above-mentioned task is achieved by a method for producing an antithrombotic coating material, including steps of: preparing a methanol solution containing a monomer represented by formula (1):

wherein in formula (1), R 1 , R 2 , and R 3 are the same as those described in the specification, respectively; adding a radical polymerization initiator having a 10-hour half-life temperature of 60° C. or less to the methanol solution to prepare a polymerization reaction liquid; and polymerizing the monomer.

First claim

What is claimed is:

1 . A method for producing an antithrombotic coating material, the method comprising:
preparing a methanol solution containing a monomer represented by formula (1):

wherein in formula (1), R 1 represents a hydrogen atom or a methyl group, R 2 represents an alkylene group having 1 to 4 carbon atoms, and R 3 represents an alkyl group having 1 to 4 carbon atoms;
adding a radical polymerization initiator having a 10-hour half-life temperature of 60° C. or less to the methanol solution to prepare a polymerization reaction liquid; and
polymerizing the monomer.

2 . The method according to claim 1 , wherein a content of the monomer contained in the polymerization reaction liquid is 10 wt % or more.

3 . The method according to claim 2 , wherein the content of the monomer contained in the polymerization reaction liquid is from 20 wt % to a saturated concentration.

4 . The method according to claim 1 , wherein a weight average molecular weight of the polymer obtained by the polymerization of the monomer is 200,000 or more.

5 . The method according to claim 4 , wherein the weight average molecular weight of the polymer obtained by the polymerization of the monomer is more than 300,000 but not more than 1,000,000.

6 . The method according to claim 1 , wherein the monomer is methoxyethyl (meth)acrylate.

7 . The method according to claim 1 , wherein the methanol solution contains methanol in an amount of 95 wt % or more, based on the total solvent content of the methanol solution.

8 . The method according to claim 1 , wherein the monomer is methoxymethyl acrylate, methoxyethyl acrylate (MEA), ethoxymethyl acrylate, ethoxyethyl acrylate, methoxymethyl methacrylate, methoxyethyl methacrylate, ethoxymethyl methacrylate, or ethoxyethyl methacrylate.

9 . The method according to claim 1 , wherein the monomer represented by formula (1) is copolymerized with a second monomer that is copolymerizable with the monomer represented by formula (1).

10 . The method according to claim 1 , wherein the radical polymerization initiator having a 10-hour half-life temperature of 60° C. or less is 2,2′-azobis(4-methoxy-2,4-dimethylvaleronitrile), 3-hydroxy-1,1-dimethylbutylperoxyneodecanoate, or α-cumyl peroxyneodecanoate.

11 . The method according to claim 1 , wherein the radical polymerization initiator having a 10-hour half-life temperature of 60° C. or less is added in an amount of 0.005 to 2 parts by weight of the monomer.

12 . The method according to claim 1 , wherein the content of the monomer contained in the polymerization reaction liquid is 10 wt % or more and 70 wt % or less.

13 . An antithrombotic coating material, comprising:
polyalkoxyalkyl (meth)acrylate that contains a structural unit (A) represented by formula (2):

wherein in formula (2), R 1 represents a hydrogen atom or a methyl group, R 2 represents an alkylene group having 1 to 4 carbon atoms, and R 3 represents an alkyl group having 1 to 4 carbon atoms,
wherein the polyalkoxyalkyl (meth)acrylate has a weight average molecular weight of 200,000 or more, and
wherein the polyalkoxyalkyl (meth)acrylate is dissolved in methanol or a mixture comprising water and methanol.

14 . The antithrombotic coating material according to claim 13 , wherein a ratio of intermediate water calculated by equation (1) below with respect to the polyalkoxyalkyl (meth)acrylate that is equilibrium-hydrated, exceeds 32%:
Ratio (%) of Intermediate Water=( a/x )×100  Equation (1):

wherein in equation (1), a and x represent an intermediate water content (wt %) and an equilibrium water content (wt %), respectively, in the polyalkoxyalkyl (meth)acrylate that is equilibrium-hydrated.

15 . The antithrombotic coating material according to claim 13 , wherein the weight average molecular weight of the polyalkoxyalkyl (meth)acrylate is less than 1,000,000.

16 . The antithrombotic coating material according to claim 13 , wherein the weight average molecular weight of the polyalkoxyalkyl (meth)acrylate is 400,000 or more and 800,000 or less.

17 . The antithrombotic coating material according to claim 13 , wherein in formula (1), R 1 is a hydrogen atom, R 2 is a methylene group or an ethylene group, and R 3 is a methyl group.

18 . The antithrombotic coating material according to claim 13 , wherein the polymer is contained in the antithrombotic coating material in an amount of 0.2 to 10 wt % based on the antithrombotic coating material.

19 . The antithrombotic coating material according to claim 13 , wherein the polyalkoxyalkyl (meth)acrylate is dissolved in a solvent consisting of methanol or a solvent mixture consisting of water and methanol.

20 . A medical device, comprising:
a substrate comprising a polymer material, and the antithrombotic coating material according to claim 13 , wherein the antithrombotic coating material is coated on a surface of the substrate.

Assignees

• Terumo Corp

Inventors

• Anzai Takao

Classifications

• A61L31/10

  Macromolecular materials · CPC title

• A61L27/54

  Biologically active materials, e.g. therapeutic substances {(A61L27/227 takes precedence)} · CPC title

• A61L33/064 Primary

  obtained by reactions only involving carbon-to-carbon unsaturated bonds (A61L33/062 takes precedence) · CPC title

• A61L29/085

  Macromolecular materials · CPC title

• A61L2300/42

  Anti-thrombotic agents, anticoagulants, anti-platelet agents · CPC title