JP2019123773A5

JP2019123773A5 -

Info

Publication number: JP2019123773A5
Application number: JP2018003539A
Authority: JP
Filing date: 2018-01-12
Publication date: 2021-08-26
Anticipated expiration: 2038-01-12

Claims

A copolymer containing each repeating unit represented by the following formula (I):

During the ceremony
x + y is an integer of 5 to 1400, n is an integer of 5 to 1400, x + y: n is in a ratio of 1: 1 to 5, and x: y is in a ratio of 1 to 60: 1.
(1) In the repeating unit with the subscript y, in L-PEG-A,
L is O or NH, and PEG is expressed by the following equation.

Here, p is an integer of 1 to 6, q is an integer of 5 to 500, and so on.
A represents A1: unsubstituted or substituted C ₁ −C ₁₂ alkoxy group, and the substituent when substituted is a formyl group, formula R ^a R ^b CH − (where R ^a and R ^b are independent). and, C ₁ -C ₄ alkoxy or R ¹ and R ² are -OCH ₂ CH ₂ O together _{-, - O (CH 2)} 3 O- or -O (CH ₂₎ represents a ₄ O-. ) Group, or A2:

Represents a group represented by, and the repeating unit accounts for 2% to 15% of the total unit of the copolymer represented by the formula (I).
(2) In the repeating unit with the subscript x
(A) Either _{R 1} or R _{2 is}
a1: The following equation

Represented by, here,
TEMPO is 2,2,6,6-tetramethylpiperidin-1-oxyl-4-yl, 2,2,5,5-tetramethylpyrrolidine-1-oxyl-3-yl, 2,2,5,5. -Tetramethylpyrroline-1-oxyl-3-yl, 2,4,4-trimethyl-1,3-oxazolidine-3-oxyl-2-yl, 2,4,4-trimethyl-1,3-thiazolidine-3 Residues of cyclic nitroxide radical compounds selected from the group consisting of −oxyl-2-yl and 2,4,4-trimethyl-imidazolidine-3-oxyl-2-yl;
a2: The following equation

Residues represented by any of;
a3: The following equation

Residues represented by any of;
a4: The following equation

Represented by, where R ₃ is _{an alkyl group of C 1-3} and r is an integer of 2-6, residues;
It is a residue selected from the group consisting of
The other is OH, or (b) R ₁ and R ₂ together represent -O-, forming a cyclic anhydride residue, or (c) R ₁ and R ₂ are each OH. was Table,
And, in the repeating unit with x,
(I) A unit containing only one of a1 to a4 in the residues defined in (a) , or
(Ii) Either a unit containing any one of a1 to a4 in the residues defined in (a) and a unit containing a group defined in (b) or a group defined in (c). One of them exists randomly independently of each other, and the unit containing any one of a1 to a4 in the residues defined in (a) is 15% of the total number of repeating units with x. Occupies ~ 60% or
(Iii) The unit containing any one of a1 to a4 in the residues defined in (a) and the unit containing the group defined in (b) or the group defined in (c) are both. Units that exist independently and randomly and contain any one of a1 to a4 in the residues defined in (a) account for 15% to 60% of the total number of repeating units with x. Or ,
(Iv) Among the residues defined in (a), a unit containing a residue of a4, a unit containing any one of a1 to a3, and a group defined in (b) or a group (c). Units containing any one of the defined groups exist independently and randomly, and units containing any one of a1 to a3 in the residues defined in (a) are marked with x. It accounts for 15% to 60% of the total number of iteration units made, or
(V) Among the residues defined in (a), a unit containing a residue of a4, a unit containing a residue of any one of a1 to a3, and a unit containing a group defined in (b) ( Units containing the group defined in c) exist independently and randomly, and units containing any one of a1 to a3 in the residues defined in (a) are labeled with x. It accounts for 15% to 60% of the total number of iteration units, or
(Vi) Among the residues defined in (a), the unit containing the residue of a4 and the unit containing the residue of a1 are both independently and randomly present .

A copolymer according to claim 1, wherein the residues defined in (a), the residue of a1, copolymer.

A copolymer according to claim 1, wherein the residues defined in (a), the residue of a2, copolymer.

A copolymer according to claim 1, wherein the residues defined in (a), the residue of a3, copolymer.

The copolymer according to claim 1, wherein the residue defined in (a) above is a unit containing the residue of a4.

The copolymer according to claim 1, wherein the residue defined in (a) above is a unit containing a residue of a1 and a residue of a4.

In the copolymer according to any one of claims 1 to 6, in the repeating unit with the subscript y, A in L-PEG-A is the formula of A2.

In a residue represented copolymer.

The copolymer according to any one of claims 1 to 7, wherein the TEMPO is the following formula.

In the above equation, R'is a methyl group,
A copolymer, which is any residue represented by.

The copolymer according to any one of claims 1 to 8, wherein the copolymer exists as nanoparticles having an average particle size of nano size when dynamic light scattering is measured in an aqueous medium.

A composite comprising the copolymer according to any one of claims 1 to 8 and benzalkonium chloride.

A medical composition comprising the copolymer according to any one of claims 1 to 8 and an anticancer agent.

The medical composition according to claim 11, wherein the anticancer agent is paclitaxel or sorafenib.

A copolymer represented by the following formula (II).

During the ceremony
Either R _1-1 or R _2-1
a1: The following equation

Residues represented by any of;
a3: The following equation

Residues represented by any of;
a4: The following equation

Represented by, where R ₃ is _{an alkyl group of C 1-3} and r is an integer of 2-6, residues;
One or more residues selected from the group consisting of
The other is OH, and the cyclic anhydride residue moiety in formula (II) may be hydrolyzed to 10% of m1 to open the ring.
And m1 + m2 is an integer of 5 to 1400, n is an integer of 5 to 1400, and m1 + m2: n is in a ratio of 1: 1 to 5.

In the repeating unit with the subscript m2, either _{R 1-1} or R _{2-1 is}
a1: The following equation

The copolymer according to claim 13.