JPWO2021104835A5

JPWO2021104835A5 -

Info

Publication number: JPWO2021104835A5
Application number: JP2022532032A
Authority: JP
Publication date: 2023-11-06

Claims

A coating for a medical device, the coating comprising:
comprising a surface layer and an optional base layer,
The coating, wherein the surface layer comprises polymer chains attached to anti-coagulation groups, the anti-coagulation groups being selected from sulfonic acid groups, sulfonamide groups, sulfamic acid groups, hydrogen sulfate groups and their conjugated bases.

The polymer chain bonded to the anti-coagulation group has the formula (C-2):
[In formula (C-2),
each Y ¹ is selected from O ⁻ , OH, NH ⁻ , and NH ₂ , preferably selected from O ⁻ and OH;
Y ² is selected from O ⁻ and OH;
each L ¹ is a C _2-5 alkene, preferably ethylene;
L ² is a C _2-5 alkene, preferably ethylene;
R ^A is selected from H and C _1-6 alkyl, preferably selected from H and methyl;
ⁿ¹ is an integer, preferably 5 or more; ⁿ² is an integer, preferably 5 or more]
Coating according to claim 1, represented by.

The polymer chain is attached to a plurality of anti-coagulant groups, each anti-coagulant group is attached to the polymer chain by a linker group, and preferably the plurality of anti-coagulant groups are attached to a plurality of sulfonic acid groups, sulfonate groups, etc. 3. A coating according to claim 1 or 2, which is a group or a combination thereof.

The polymer chain has the formula (A-1):
[In the above formula (A-1),
X ^1A is selected from O ⁻ , OH, OR ^1A , NH ₂ , NHR ^1A and A ^1A ;
X ^1B is selected from O ⁻ , OH, OR ^1B , NH ₂ , NHR ^1B and A ^1B ;
each of R ^1A and R ^1B is independently selected from C _1-6 alkyl, C _6-10 aryl and C _6-10 aryl- _{C 1-6} alkyl;
Each of A ^1A and A ^1B independently represents the formula (S-1):
{In the above formula (S-1),
Z ¹ is selected from O, NH and NR ¹
R ¹ is selected from C _1-6 alkyl, C _6-10 aryl and C _6-10 aryl-C _1-6 alkyl;
Y ¹ is selected from O ⁻ and OH,
L ¹ is the formula (L-1):
[In the above formula (L-1),
P ¹ is selected from a single bond, C _1-10 alkene, C _2-10 alkenylene, C _2-10 alkynylene and phenylene;
Q ¹ is selected from a single bond, O, NH, NR ^1C and phenylene;
W ¹ is selected from a single bond, C _1-10 alkene, C _2-10 alkenylene, C _2-10 alkynylene and phenylene;
R ^1C is selected from C _1-6 alkyl, C _6-10 aryl and C _6-10 aryl-C _1-6 alkyl.
represented by}
]
Coating according to claim 1 or 2, comprising a repeating unit represented by.

(a) at least one of X ^1A is A ^1A or X ^1B is A ^1B ; or (b) both X ^1A are A ^1A and X ^1B is A ^1B . Coating as described.

each Z ¹ is selected from O and NH;
Coating according to claim 4 or 5, preferably each Z ¹ is NH.

each P ¹ is selected from C _1-10 alkene, C _2-10 alkenylene and C _2-10 alkynylene;
Each Q ¹ is a single bond,
Each W ¹ is a single bond,
Coating according to any one of claims 4 to 6, preferably each P ¹ is C _1-10 alkylene, any C _2-6 alkylene, or more preferably each ^P 1 is ethylene. .

each P ¹ is selected from C _1-10 alkylene, C _2-10 alkenylene and C _2-10 alkynylene;
each Q ¹ is selected from O, NH and NR ^1C ;
Each W ¹ is a single bond,
Coating according to any one of claims 4 to 6, wherein preferably each Q ¹ is selected from O and NH.

The polymer chain has the formula (B-1):
[In formula (B-1),
R ^A is selected from H and C _1-6 alkyl;
^X2 is selected from ^O- , OH, ^OR2A , _NH2 , ^NHR2A and ^A2 ,
R ^2A is selected from C _1-6 alkyl, C _6-10 aryl and C _6-10 aryl-C _1-6 alkyl;
^A2 is the formula (S-2):

{In formula (S-2),
^Z2 is selected from O, NH and ^NR2 ;
R ² is selected from C _1-6 alkyl, C _6-10 aryl and C _6-10 aryl-C _1-6 alkyl;
Y ² is selected from O ⁻ and OH;
L ² is the formula (L-2):

[In formula (L-2),
P ² is selected from a single bond, C _1-10 alkylene, C _2-10 alkenylene, C _2-10 alkynylene and phenylene;
^Q2 is selected from a single bond, O, NH, ^NR2C and phenylene;
W ² is selected from a single bond, C _1-10 alkene, C _2-10 alkenylene, C _2-10 alkynylene and phenylene;
R ^2C is selected from C _1-6 alkyl, C _6-10 aryl and C _6-10 aryl-C _1-6 alkyl.
represented by}
]
Coating according to claim 1 or 2, comprising a repeating unit represented by.

10. The coating according to claim 9, wherein ^X2 is ^A2 .

R ^A is selected from H and methyl;
Coating according to claim 9 or 10, preferably R ^A is H.

^Z2 is selected from O and NH;
Coating according to any one of claims 9 to 11, wherein preferably Z ² is NH.

P ² is selected from C _1-10 alkylene, C _2-10 alkenylene and C _2-10 alkynylene;
^Q2 is a single bond,
W ² is a single bond,
Coating according to any one of claims 9 to 12, wherein preferably P ² is C _1-10 alkylene, optionally C _2-6 alkylene, or more preferably P ² is ethylene.

P ² is selected from C _1-10 alkylene, C _2-10 alkenylene and C _2-10 alkynylene;
^Q2 is selected from O, NH and ^NR2C ;
W ² is a single bond,
Coating according to any one of claims 9 to 12, wherein preferably Q ² is selected from O and NH.

The polymer chain has the formula (C-1):
[In formula (C-1),
Each of X ^1A , X ^1B , R ^1A , R ^1B , A ^1A , A ^1B , Z ¹ , R 1 , Y ¹ , L ¹ , ^{P 1 , Q 1 and W 1} ^is ^defined ⁱⁿ claims 4 to 8. As it is,
R ^A , X ² , R ^2A , ^A ² , Z ² , R ² , Y ² , L ² , P ² , Q 2 and W ² are as defined in claims 9 to 14;
n ¹ is an integer,
n ² is an integer]
Coating according to any one of claims 3 to 14, which is a block copolymer represented by.

Coating according to claim 15, wherein R ^A is selected from H and methyl, preferably R ^A is H.

At least one of X ^1A , X ^1B and X ² is A ^1A , A ^1B and A ² , respectively;
17. A coating according to claim 15 or 16, wherein preferably ^X2 is ^A2 and at least one of ^X1A and ^X1B is ^A1A and ^A1B , respectively.

each Z ¹ is selected from O and NH, Z ² is selected from O and NH,
Coating according to any one of claims 15 to 17, wherein preferably Z ² and each Z ¹ are NH.

each P ¹ is selected from C _1-10 alkylene, C _2-10 alkenylene and C _2-10 alkynylene;
Each Q ¹ is a single bond,
Each W ¹ is a single bond,
P ² is selected from C _1-10 alkylene, C _2-10 alkenylene and C _2-10 alkynylene;
^Q2 is a single bond,
W ² is a single bond,
Preferably each P ¹ is C _1-10 alkylene, P ² is C _1-10 alkylene, optionally each P ¹ and P ² is C _2-6 alkylene, or
Coating according to any one of claims 15 to 18, more preferably each P ¹ and P ² is ethylene.

each P ¹ is selected from C _1-10 alkylene, C _2-10 alkenylene and C _2-10 alkynylene;
each Q ¹ is selected from O, NH and NR ^1C ;
Each W ¹ is a single bond,
P ² is selected from C _1-10 alkylene, C _2-10 alkenylene and C _2-10 alkynylene;
^Q2 is selected from O, NH and ^NR2C ;
W ² is a single bond,
Coating according to any one of claims 15 to 18, wherein preferably each Q ¹ is selected from O and NH and Q ² is selected from O and NH.

n ¹ is 5-500 and/or n ² is 5-500,
Coating according to any one of claims 15 to 20, wherein preferably n ¹ is from 10 to 300 and n ² is from 10 to 300.

comprising the base layer;
The base layer comprises protein;
Coating according to any one of claims 1 to 21 , wherein preferably the protein is human albumin.

Medical device having a surface coated with a coating according to any one of claims 1 to 22.

A method for producing a coating for a medical device, the method comprising:
binding a compound comprising an anticoagulant to the polymer using a coupling agent;
The compound comprising an anti-coagulation group has the formula (E-1):
[In (E-1) above,
^Z3 is selected from OH, _NH2 and ^NHR3 ;
R ³ is selected from C _1-6 alkyl, C _6-10 aryl and C _6-10 aryl-C _1-6 alkyl;
^L3 is the formula (L-3):
{In formula (L-3),
P ³ is selected from a single bond, C _1-10 alkylene, C _2-10 alkenylene, C _2-10 alkynylene and phenylene;
^Q3 is selected from a single bond, O, NH, ^NR3C and phenylene;
W ³ is selected from a single bond, C _1-10 alkylene, C _2-10 alkenylene, C _2-10 alkynylene and phenylene;
R ^3C is selected from C _1-6 alkyl, C _6-10 aryl and C _6-10 aryl-C _1-6 alkyl}
]
is expressed by
The polymer has the formula (D-1):
[In formula (D-1), X ³ is selected from OH, OR ^3A , NH ₂ and NHR ^3A , R ^3A is C _1-6 alkyl, C _6-10 aryl and C _6-10 aryl-C selected from _1-6 alkyl]
A method comprising a repeating unit represented by.

(a) a polymer as defined in claim 24;
(b) a compound comprising an anticoagulation group as defined in claim 24;
A kit for coating a medical device, comprising: (c) a coupling agent; and (d) the optional coating for forming a base layer.

Coating or claim according to any one of claims 1 to 22 for use in the treatment of the human or animal body by surgery or therapy and/or in diagnostic methods carried out on the human or animal body. The medical device according to item 23.

A coating according to any one of claims 1 to 22, a medical device according to claim 23, or a coating for use according to claim 26 for use in reducing or preventing blood coagulation. Medical device for use.

contacting the medical device with blood;
24. A method of reducing or preventing blood coagulation, wherein the medical device is defined in claim 23.