CN114502603A

CN114502603A - Degradable polymer material

Info

Publication number: CN114502603A
Application number: CN202080071087.5A
Authority: CN
Inventors: 後藤淳; 胡欣怡; 葛轶岑
Original assignee: Nanyang Technological University
Current assignee: Nanyang Technological University
Priority date: 2019-10-11
Filing date: 2020-10-09
Publication date: 2022-05-13
Also published as: WO2021071432A1; JP2022553490A

Abstract

Disclosed herein are degradable polymeric materials comprising polymers of formula I, and methods of forming the polymeric materials. The polymer of formula I has the following structure: wherein m, n, X₁、X₂、R₁To R₃And Y is as defined herein.

Description

Degradable polymer material

Technical Field

The present invention relates to degradable polymeric materials, and methods of forming the same.

Background

The listing or discussion of a prior-published document in this specification should not necessarily be taken as an acknowledgement that the document is part of the state of the art or is common general knowledge.

Synthetic polymers are ubiquitous and present in almost all materials used in our daily lives. However, most of these synthetic polymers are not degradable and tend to remain in the natural environment as waste products, contaminating and damaging the natural ecosystem. Thus, there is a great need in the industry to develop degradable synthetic polymers to improve sustainability. In 2017, the global biodegradable polymer market reaches 484.7 kilotons, and is predicted to increase to 984.8 kilotons by 2022, and the composite annual growth rate of the time period of 2017 and 2022 is 15.2%.

Radical polymerization is by far one of the most important techniques for synthesizing polymers, and industrially up to 50% of synthetic polymers (based on value) are produced by this method. However, this approach generally results in synthetic polymers that cannot be readily decomposed due to the presence of a strong carbon-carbon backbone.

Cyclic Ketene Acetals (CKA) have been used as monomers in free radical polymerization to create degradable ester bonds in the polymer backbone (see fig. 2 a). Typically, CKA and other vinyl monomers are mixed and copolymerized to produce degradable polymers with ester linkages. While CKA can undergo ring opening during polymerization to produce ester linkages, in many cases a significant amount of CKA also undergoes ring retention without producing ester linkages. These environmentally friendly leave-on structures are not degradable, and thus CKA cannot be used to efficiently produce degradable polymers.

Therefore, there is a need to develop new degradable polymers to solve one or more of the above problems. Importantly, these polymers must be highly versatile and functional, and easy and inexpensive to mass produce. Such degradable polymers can potentially be incorporated as materials into, for example, disposable and packaging articles, as well as for medical applications.

Stimuli-responsive degradable polymers are examples of degradable polymers that are highly sought in a range of high-value materials. These polymers are highly functional and can form nanocapsules (e.g. micelles, vesicles) for containing useful active compounds for various applications, such as drugs, genes, pesticides and cosmetics. Depending on the stimuli-responsive nature of such polymers, the active compounds may be released in a controlled manner in response to pH, temperature, water, light, enzymes and natural conditions.

Disclosure of Invention

Aspects and embodiments of the present invention will now be described with reference to the following numbered clauses.

1. A degradable polymeric material comprising a polymer of formula I:

wherein:

m has a non-zero integer value;

n has a value of 0 or a non-zero integer value;

X₁and X₂Independently selected from O, NR_aOr S;

R_ais H or C₁To C₆An alkyl group;

R₁and R₂Independently selected from halogen, heteroaromatic group or more particularly alkyl group, aromatic group, ether group, ester group, ketone, hydroxyl group, carboxylic acid group or amine group, with the proviso that R₁And R₂Only one of which may be OH;

when present, R₃Is H or C₁To C₆An alkyl group;

when present, Y is selected from:

An aromatic or heteroaromatic ring system which is unsubstituted or selected from halogen, C₁To C₆Alkyl, OR_4a、NR_4bR_4c、SO₃H and B (OH)₂Substituted with one or more groups of (a);

CN；

C₁to C₂₀An alkyl group which is unsubstituted or substituted by one or more of: halogen, aromatic or heteroaromatic ring systems (said aromatic or heteroaromatic ring systems being unsubstituted or selected from halogen, C₁To C₆Alkyl, OR_5aAnd NR_5bR_5cSubstituted with one or more groups of (a)), an epoxy group, a cycloalkyl ring system (said cycloalkyl ring system being unsubstituted or selected from halogen, C₁To C₆Alkyl, OR_5dAnd NR_5eR_5fSubstituted with one OR more groups of (a), OR_5g、Si(OR_5h)₃、NR_5iR_5jAnd N⁺R_5kR_5lR_5m；

OR_6a；

-C(＝O)OR_6b；

-A-(OLO)_p-R₇；

R_4aTo R_4c、R_5aTo R_5gAnd R_5iTo R_5mEach independently represents H or C₁To C₆An alkyl group;

each R_5hIndependently represent C₁To C₆An alkyl group;

R_6aand R_6bEach independently represents:

H；

C₁to C₂₀An alkyl group which is unsubstituted or substituted by one or more of: halogen, aromatic or heteroaromatic ring systems (said aromatic or heteroaromatic ring systems being unsubstituted or selected from halogen, C₁To C₆Alkyl, OR_8aAnd NR_8bR_8cSubstituted with one or more groups of (a)), an epoxy group, a cycloalkyl ring system (said cycloalkyl ring system being unsubstituted or selected from halogen, C₁To C₆Alkyl, OR_8dAnd NR _8eR_8fSubstituted with one OR more groups of (a), OR_8g、Si(OR_8h)₃、NR_8iR_8jAnd N⁺R_8kR_8lR_8m；

Cycloalkyl ring systems (said cycloalkyl ring systems being unsubstituted or selected from halogen, C₁To C₆Alkyl, OR_9aAnd NR_9bR_9cSubstituted with one or more groups of (a);

a represents a bond or is-C (═ O) -;

l represents an alkyl chain of 2 to 10 carbon atoms;

p has a value of 1 to 1000;

R₇is represented by C₁To C₂₀An alkyl group which is unsubstituted or substituted by one or more of: halogen, aromatic or heteroaromatic ring systems (said aromatic or heteroaromatic ring systems being unsubstituted or selected from halogen, C₁To C₆Alkyl, OR_10aAnd NR_10bR_10cSubstituted with one or more groups of (a)), an epoxy group, a cycloalkyl ring system (said cycloalkyl ring system being unsubstituted or selected from halogen, C₁To C₆Alkyl, OR_10dAnd NR_10eR_8fSubstituted with one OR more groups of (a), OR_10g、Si(OR_10h)₃、NR_10iR_10jAnd N⁺R_10kR_10lR_10m；

R_8aTo R_8g、R_8iTo R_8m、R_9aTo R_9c、R_10aTo R_10g、R_10iTo R_10mEach independently represents H or C₁To C₆An alkyl group;

R_8hand R_10hEach independently represents C₁To C₆An alkyl group, a carboxyl group,

and salts or solvates thereof.

2. The degradable polymeric material of clause 1, wherein the polymeric material further comprises a polymer of formula II:

wherein, X₁、X₂、m、n、R₁To R₃And the value of Y is as defined in clause 1.

3. The degradable polymeric material of clause 1 or clause 2, wherein X ₁And X₂Is O, and X₁And X₂Is independently selected from O, NR_aOr S.

4. The degradable polymeric material of any one of the preceding clauses wherein X is₁And X₂Both are O.

5. The degradable polymeric material of any one of the preceding clauses wherein R is₁And R₂Independently selected from alkyl groups and aromatic groups.

6. The degradable polymeric material of clause 5, wherein R₁And R₂Independently selected from C₁To C₃An alkyl group and a phenyl group, optionally wherein R₁And R₂Both being methyl radicals or R₁Is a methyl group and R₂Is a phenyl group.

7. The degradable polymeric material of any one of the preceding clauses wherein n has a non-zero integer value, optionally wherein the polymer is a random copolymer, a block copolymer, or has a portion corresponding to a random copolymer and a portion corresponding to a block copolymer (e.g., the polymer is a random copolymer or a block copolymer, such as a random copolymer).

8. The degradable polymeric material of any one of the preceding clauses wherein, when present, the repeating unit of formula Ia in formula I or formula II:

formed from monomers selected from one or more of the group consisting of styrene, acrylates, methacrylates, acrylamides, and methacrylamides.

9. The degradable polymeric material of clause 8 wherein, when present, the recurring unit of formula Ia in formula I or formula II:

formed from monomers selected from one or more of the group consisting of: acrylonitrile and styreneMethoxystyrene, butoxystyrene, chloromethylstyrene, chlorostyrene, methyl acrylate, ethyl acrylate, propyl acrylate, n-butyl acrylate, tert-butyl acrylate, hexyl acrylate, 2-ethylhexyl acrylate, n-octyl acrylate, nonyl acrylate, decyl acrylate, benzyl acrylate, tetrahydrofurfuryl acrylate, glycidyl acrylate, cyclohexyl acrylate, 2-methoxyethyl acrylate, and butoxyethyl acrylate, tris (trialkylsiloxy) derivatives-acrylates and fluoroalkyl acrylates, methyl methacrylate, ethyl methacrylate, propyl methacrylate, n-butyl methacrylate, tert-butyl methacrylate, hexyl methacrylate, 2-ethylhexyl methacrylate, n-octyl methacrylate, nonyl methacrylate, n-butyl acrylate, and n-butyl acrylate, and/2-acrylate, and/or a, Decyl methacrylate, benzyl methacrylate, tetrahydrofurfuryl methacrylate, glycidyl methacrylate, cyclohexyl methacrylate, 2-methoxyethyl methacrylate, butoxyethyl methacrylate, tris (trialkylsiloxy) derivative-methacrylate, fluoroalkyl methacrylate, hydroxystyrene, styrenesulfonic acid, sodium styrenesulfonate, styrene boric acid, acrylamide, N-isopropylacrylamide, N-dimethylacrylamide, N-methylolacrylamide, N-hydroxyethylacrylamide, methacrylamide, N-isopropylmethacrylamide, N-dimethylmethacrylamide, N-methylolmethacrylamide, N-hydroxyethylmethacrylamide, acrylic acid, hydroxyalkyl acrylates (e.g.2-hydroxyethyl acrylate), 2-hydroxypropyl acrylate, glycerol monoacrylate, diethylene glycol acrylate, polyethylene glycol acrylate, methoxytetraethylene glycol acrylate, methoxypolyethylene glycol acrylate, 2- (dimethylamino) ethyl acrylate, 3-chloro-2-hydroxypropyl acrylate, 2-hydroxy-3-phenoxypropyl acrylate, 2-acryloyloxyethylphosphorylcholine, 2- (N, N-diethyl-N-methylamino) ethyl acrylate +/trifluoromethanesulfoniinium acrylate, 2- (N-ethyl-N-methyl-N-hydroamino) ethyl acrylate +/trifluoromethanesulfoniinium acrylate (N (CF) ₃SO₂)^2-) Salt, 1-ethyl-3-methylimidazolium acrylate +/fluorohydrogenate ((FH) nF)^-) Salt, methacrylic acid2-hydroxyethyl methacrylate, 2-hydroxypropyl methacrylate, glycerol monomethacrylate, diethylene glycol methacrylate and polyethylene glycol methacrylate, methoxy tetraethylene glycol methacrylate, methoxy polyethylene glycol methacrylate, 2- (dimethylamino) ethyl methacrylate, 3-chloro-2-hydroxypropyl methacrylate, 2-hydroxy-3-phenoxypropyl methacrylate, 2-acryloyloxyethyl phosphorylcholine, 2- (N) methacrylate, N-diethyl-N-methylamino) ethyl ester +/trifluorosulfonyliminium salt, 2- (N-ethyl-N-methyl-N-hydroamino) ethyl methacrylate +/trifluorosulfonyliminium (N (CF).₃SO₂)^2-) Salt and 1-ethyl-3-methylimidazolium methacrylate +/fluorohydrogenate ((FH) nF^-) And (3) salt.

10. The degradable polymeric material of clause 8 or clause 9, wherein, when present, the recurring unit of formula Ia in formula I or formula II:

formed from monomers selected from one or more of the group consisting of: methyl Methacrylate (MMA), Butyl Acrylate (BA) (e.g., n-butyl acrylate), Acrylonitrile (AN), poly (ethylene glycol) methyl ether methacrylate (PEGMA), Butyl Methacrylate (BMA) (e.g., n-butyl methacrylate), styrene (St), and 2-methoxyethyl acrylate (MEA).

11. The degradable polymeric material of any one of the preceding clauses wherein, when present, R₃Is H or C₁To C₃Alkyl, optionally wherein R₃Is H or methyl.

12. The degradable polymeric material of any one of the preceding clauses wherein, when present, Y is selected from:

a benzene ring, unsubstituted or selected from halogen, C₁To C₃Alkyl, OR_4a、SO₃H and B (OH)₂Substituted with one or more groups of (a);

CN；

C₁to C₁₀An alkyl group which is unsubstituted or substituted by one or more of: halogen, benzene ring (the benzene ring is unsubstituted or selected from halogen, C₁To C₃Alkyl, OR_5aAnd NR_5bR_5cSubstituted with one or more groups of (a)), an epoxy group, a cycloalkyl ring system (said cycloalkyl ring system being unsubstituted or selected from halogen, C₁To C₃Alkyl, OR_5dAnd NR_5eR_5fSubstituted with one OR more groups of (a), OR_5g、Si(OR_5h)₃、NR_5iR_5jAnd N⁺R_5kR_5lR_5m；

OR_6a；

-C(＝O)OR_6b；

-A-(OLO)_p-R₇；

R_4a、R_5aTo R_5gAnd R_5iTo R_5mEach independently represents H or C₁To C₆An alkyl group;

each R_5hIndependently represent C₁To C₆An alkyl group;

R_6aand R_6bEach independently represents:

H；

C₁to C₁₀An alkyl group which is unsubstituted or substituted by one or more of: halogen, aromatic or heteroaromatic ring systems (said aromatic or heteroaromatic ring systems being unsubstituted or selected from halogen, C ₁To C₆Alkyl, OR_8aAnd NR_8bR_8cSubstituted with one or more groups of (a)), an epoxy group, a cycloalkyl ring system (said cycloalkyl ring system being unsubstituted or selected from halogen, C₁To C₆Alkyl, OR_8dAnd NR_8eR_8fSubstituted with one OR more groups of (a), OR_8g、Si(OR_8h)₃、NR_8iR_8jAnd N⁺R_8kR_8lR_8m；

Cycloalkyl ring system (said cycloalkyl group)The ring system being unsubstituted or selected from halogen, C₁To C₆Alkyl, OR_9aAnd NR_9bR_9cSubstituted with one or more groups of (a);

a represents a bond or is-C (═ O) -;

l represents an alkyl chain of 2 to 4 carbon atoms;

p has a value of 5 to 500;

R₇is represented by C₁To C₁₀An alkyl group which is unsubstituted or substituted by one or more of: halogen, aromatic or heteroaromatic ring systems (said aromatic or heteroaromatic ring systems being unsubstituted or selected from halogen, C₁To C₆Alkyl, OR_10aAnd NR_10bR_10cSubstituted with one or more groups of (a)), an epoxy group, a cycloalkyl ring system (said cycloalkyl ring system being unsubstituted or selected from halogen, C₁To C₆Alkyl, OR_10dAnd NR_10eR_8fSubstituted with one OR more groups of (a), OR_10g、Si(OR_10h)₃、NR_10iR_10jAnd N⁺R_10kR_10lR_10m；

R_8aTo R_8g、R_8iTo R_8m、R_9aTo R_9c、R_10aTo R_10g、R_10iTo R_10mEach independently represents H or C₁To C₃An alkyl group;

R_8hand R_10hEach independently represents C₁To C₃An alkyl group.

13. The degradable polymeric material of clause 12 wherein when present, Y is selected from:

CN；

C₁to C₆An alkyl group which is unsubstituted or substituted by one or more of: halogen, benzene ring (said benzene ring is not taken)Substituted or selected from halogen, C₁To C₃Alkyl, OR_5aAnd NR_5bR_5cIs substituted with one or more groups), an epoxy group, a cyclohexane ring, a cyclopentane ring (the cyclohexane or cyclopentane ring is unsubstituted or is selected from halogen, C₁To C₃Alkyl, OR_5dAnd NR_5eR_5fSubstituted with one OR more groups of (a), OR_5g、Si(OR_5h)₃、NR_5iR_5jAnd N⁺R_5kR_5lR_5m；

OR_6a；

-C(＝O)OR_6b；

-A-(OLO)_p-R₇；

each R_5hIndependently represent C₁To C₆An alkyl group;

R_6aand R_6bEach independently represents:

H；

C₁to C₆An alkyl group which is unsubstituted or substituted by one or more of: halogen, aromatic or heteroaromatic ring systems (said aromatic or heteroaromatic ring systems being unsubstituted or selected from halogen, C₁To C₆Alkyl, OR_8aAnd NR_8bR_8cSubstituted with one or more groups of (a)), an epoxy group, a cycloalkyl ring system (said cycloalkyl ring system being unsubstituted or selected from halogen, C₁To C₆Alkyl, OR_8dAnd NR_8eR_8fSubstituted with one OR more groups of (a), OR_8g、Si(OR_8h)₃、NR_8iR_8jAnd N⁺R_8kR_8lR_8m；

Cycloalkyl ring systems (said cycloalkyl ring systems being unsubstituted or selected from halogen, C ₁To C₆Alkyl, OR_9aAnd NR_9bR_9cOne or more ofSubstituted with radicals);

a represents a bond or is-C (═ O) -;

l represents an alkyl chain of 2 to 4 carbon atoms;

p has a value of 10 to 250;

R₇is represented by C₁To C₆An alkyl group which is unsubstituted or substituted by one or more of: halogen, aromatic or heteroaromatic ring systems (said aromatic or heteroaromatic ring systems being unsubstituted or selected from halogen, C₁To C₆Alkyl, OR_10aAnd NR_10bR_10cSubstituted with one or more groups of (a)), an epoxy group, a cycloalkyl ring system (said cycloalkyl ring system being unsubstituted or selected from halogen, C₁To C₆Alkyl, OR_10dAnd NR_10eR_8fSubstituted with one OR more groups of (a), OR_10g、Si(OR_10h)₃、NR_10iR_10jAnd N⁺R_10kR_10lR_10m；

R_8hand R_10hEach independently represents C₁To C₃An alkyl group.

14. The degradable polymeric material of any of the preceding clauses wherein when n has a non-zero integer value, the [ sic ], [ solution of ] is]_mThe repeating units in the degradable polymer material account for 0.01 to 99.99mol percent of the degradable polymer material.

15. The degradable polymeric material of clause 14, wherein when n has a non-zero integer value, [ 2 ]]_mThe repeating units within constitute 0.05 to 50 mol%, such as 0.1 to 30 mol%, such as 0.5 to 10 mol%, such as 1 to 5 mol% of the degradable polymeric material.

16. The degradable polymeric material of any one of the preceding clauses wherein the degradable polymeric material has a number average molecular weight (M)_n) Is from 150 to 10,000,000 daltons, such as from 500 to 5,000,000 daltons, such as from 1,000 to 1,000,000 daltons.

17. The degradable polymeric material of any one of the preceding clauses wherein the degradable polymeric material has a number average molecular weight (M)_n) From 500 to 200,000 daltons, such as from 2,000 to 100,000 daltons.

18. A degradable polymeric material comprising a polymer of formula III:

wherein:

m has a non-zero integer value;

n has a value of 0 or a non-zero integer value;

X₁and X₂Independently selected from O, NR_aOr S;

R_ais H or C₁To C₆An alkyl group;

R₁₁to R₁₆Independently selected from H, halogen, alkyl group, aromatic group, ether group, ester group, ketone, hydroxyl group, carboxylic acid group or amine group, with the proviso that R₁₁And R₁₂、R₁₃And R₁₄And R₁₅And R₁₆Only one of them may be OH, or

R₁₃To R₁₆Together with the carbon atoms to which they are attached form a benzene ring, unsubstituted or selected from halogen, C₁To C₆Alkyl, OR_17aAnd NR_17bR_17cSubstituted with one or more groups;

when present, R₃Is H or C₁To C₆An alkyl group;

When present, Y is selected from:

CN；

OR_6a；

-C(＝O)OR_6b；

-A-(OLO)_p-R₇；

R_4aTo R_4c、R_5aTo R_5g、R_5iTo R_5mAnd R_17aTo R_17cEach independently represents H or C₁To C₆An alkyl group;

each R_5hIndependently represent C₁To C₆An alkyl group;

R_6aand R_6bEach independently represents:

H；

C₁to C₂₀An alkyl group which is unsubstituted or substituted by one or more of: halogen, aromatic or heteroaromatic ring systems (said aromatic or heteroaromatic ring systems being unsubstituted or selected from halogen, C₁To C₆Alkyl, OR_8aAnd NR_8bR_8cSubstituted with one or more groups of (a)), an epoxy group, a cycloalkyl ring system (said cycloalkyl ring system being unsubstituted or selected from halogen, C ₁To C₆Alkyl, OR_8dAnd NR_8eR_8fSubstituted with one OR more groups of (a), OR_8g、Si(OR_8h)₃、NR_8iR_8jAnd N⁺R_8kR_8lR_8m；

a represents a bond or is-C (═ O) -;

l represents an alkyl chain of 2 to 10 carbon atoms;

p has a value of 1 to 1000;

and salts or solvates thereof.

19. The degradable polymeric material of clause 18, wherein the polymeric material further comprises a polymer of formula IV:

wherein, X₁、X₂、m、n、R₃、R₁₁To R₁₆And the value of Y is as defined in clause 18.

20. The degradable polymeric material of clause 18 or clause 19, wherein X is ₁And X₂Is O, and X₁And X₂Is independently selected from O, NR_aOr S.

21. The degradable polymeric material of any of clauses 18 to 20 wherein X₁And X₂Both are O.

22. The degradable polymeric material of any one of clauses 18 to 21 wherein R₁₁To R₁₆Independently selected from H, alkyl groups and aromatic groups, or R₁₃To R₁₆Together with the carbon atoms to which they are attached form an unsubstituted benzene ring.

23. The degradable polymeric material of clause 22, wherein R₁₁To R₁₆Independently selected from H, C₁To C₃Alkyl radicals and phenyl radicals, or R₁₃To R₁₆Together with the carbon atoms to which they are attached form an unsubstituted benzene ring.

24. The degradable polymeric material of any of clauses 18-23 wherein n has a non-zero integer value, optionally wherein the polymer is a random copolymer, a block copolymer, or has a portion corresponding to a random copolymer and a portion corresponding to a block copolymer (e.g., the polymer is a random copolymer or a block copolymer, such as a random copolymer).

25. The degradable polymeric material of any one of clauses 18 to 24 wherein, when present, the repeating unit of formula Ia in formula III or formula IV:

26. The degradable polymeric material of clause 25 wherein, when present, the recurring unit of formula Ia in formula III or formula IV:

formed from monomers selected from one or more of the group consisting of: acrylonitrile, styrene, methoxystyrene, butoxystyrene, chloromethylstyrene, chlorostyrene, methyl acrylate, ethyl acrylate, propyl acrylate, n-butyl acrylate, t-butyl acrylate, hexyl acrylate, 2-ethylhexyl acrylate, n-octyl acrylate, nonyl acrylate, decyl acrylate, benzyl acrylate, tetrahydrofurfuryl acrylate, glycidyl acrylate, cyclohexyl acrylate, 2-methoxyethyl acrylate and butoxyethyl acrylate, tris (trialkylsiloxy) derivative-acrylic acid ester and fluoroalkyl acrylate, methyl methacrylate, ethyl methacrylate, propyl methacrylate, n-butyl methacrylate, t-butyl methacrylate, hexyl methacrylate, 2-ethylhexyl methacrylate, n-octyl methacrylate, n-butyl acrylate, or a, Nonyl methacrylate, decyl methacrylate, benzyl methacrylate, tetrahydrofurfuryl methacrylate, glycidyl methacrylate, cyclohexyl methacrylate, 2-methoxyethyl methacrylate, butoxyethyl methacrylate, tris (trialkylsiloxy) derivative-methacrylate, fluoroalkyl methacrylate, hydroxystyrene, styrenesulfonic acid, sodium styrenesulfonate, styreneboric acid, acrylamide, N-isopropylacrylamide, N-dimethylacrylamide, N-methylolacrylamide, N-hydroxyethylacrylamide, methacrylamide, N-isopropylacrylamide, N-dimethylmethacrylamide, N-methylolmethacrylamide, N-hydroxyethylmethacrylamide, N-methylolmethacrylamide, N-methylol methacrylamide, N-methylol acrylamide, N-alkyl methacrylate, N-hydroxy-methyl methacrylate, N-ethyl methacrylate, N-methyl methacrylate, N-N-methyl acrylate, N-N-methyl methacrylate, N-N-butyl acrylate, acrylic acid, hydroxyalkyl acrylates (e.g. 2-hydroxyethyl acrylate), 2-hydroxypropyl acrylate, glycerol monoacrylate, diethylene glycol acrylate Esters, polyethylene glycol acrylate, methoxytetraethylene glycol acrylate, methoxypolyethylene glycol acrylate, 2- (dimethylamino) ethyl acrylate, 3-chloro-2-hydroxypropyl acrylate, 2-hydroxy-3-phenoxypropyl acrylate, 2-acryloyloxyethyl phosphorylcholine, 2- (N, N-diethyl-N-methylamino) ethyl acrylate +/trifluoromethanesulfonylimide, 2- (N-ethyl-N-methyl-N-hydro-amino) ethyl acrylate +/trifluoromethanesulfonylimide (N (CF)₃SO₂)^2-) Salt, 1-ethyl-3-methylimidazolium acrylate +/fluorohydrogenate ((FH) nF^-) Salts, methacrylic acid, 2-hydroxyethyl methacrylate, 2-hydroxypropyl methacrylate, glycerol monomethacrylate, diethylene glycol methacrylate and polyethylene glycol methacrylate, methoxy tetraethylene glycol methacrylate, methoxy polyethylene glycol methacrylate, 2- (dimethylamino) ethyl methacrylate, 3-chloro-2-hydroxypropyl methacrylate, 2-hydroxy-3-phenoxypropyl methacrylate, 2-acryloyloxyethyl phosphorylcholine, 2- (N, N-diethyl-N-methylamino) ethyl ester +/trifluorosulfonyliminium salt, 2- (N-ethyl-N-methyl-N-hydroamino) ethyl methacrylate +/trifluorosulfonyliminium (N (CF). ₃SO₂)^2-) Salt and 1-ethyl-3-methylimidazolium methacrylate +/fluorohydrogenate ((FH) nF^-) And (3) salt.

27. The degradable polymeric material of clause 25 or clause 26, wherein, when present, the recurring unit of formula Ia in formula III or formula IV:

formed from monomers selected from one or more of the group consisting of: methyl Methacrylate (MMA), Butyl Acrylate (BA) (e.g., n-butyl acrylate), Acrylonitrile (AN), poly (ethylene glycol) methyl ether methacrylate (PEGMA), n-Butyl Methacrylate (BMA) (e.g., n-butyl methacrylate), styrene (St), and 2-methoxyethyl acrylate (MEA).

28. The method of any of clauses 18-27Degrading a polymeric material, wherein, when present, R₃Is H or C₁To C₃Alkyl, optionally wherein R₃Is H or methyl.

29. The degradable polymeric material of any one of clauses 18 to 28 wherein when present, Y is selected from the group consisting of:

CN；

C₁to C₁₀An alkyl group which is unsubstituted or substituted by one or more of: halogen, benzene ring (the benzene ring is unsubstituted or selected from halogen, C ₁To C₃Alkyl, OR_5aAnd NR_5bR_5cSubstituted with one or more groups of (a)), an epoxy group, a cycloalkyl ring system (said cycloalkyl ring system being unsubstituted or selected from halogen, C₁To C₃Alkyl, OR_5dAnd NR_5eR_5fSubstituted with one OR more groups of (a), OR_5g、Si(OR_5h)₃、NR_5iR_5jAnd N⁺R_5kR_5lR_5m；

OR_6a；

-C(＝O)OR_6b；

-A-(OLO)_p-R₇；

each R_5hIndependently represent C₁To C₆An alkyl group;

R_6aand R_6bEach independently represents:

H；

C₁to C₁₀An alkyl group which is unsubstituted or substituted by one or more of: halogen, aromatic or heteroaromatic ring systems (said aromatic or heteroaromatic ring systems being unsubstituted or selected)From halogen, C₁To C₆Alkyl, OR_8aAnd NR_8bR_8cSubstituted with one or more groups of (a)), an epoxy group, a cycloalkyl ring system (said cycloalkyl ring system being unsubstituted or selected from halogen, C₁To C₆Alkyl, OR_8dAnd NR_8eR_8fSubstituted with one OR more groups of (a), OR_8g、Si(OR_8h)₃、NR_8iR_8jAnd N⁺R_8kR_8lR_8m；

a represents a bond or is-C (═ O) -;

l represents an alkyl chain of 2 to 4 carbon atoms;

p has a value of 5 to 500;

R₇is represented by C₁To C₁₀An alkyl group which is unsubstituted or substituted by one or more of: halogen, aromatic or heteroaromatic ring systems (said aromatic or heteroaromatic ring systems being unsubstituted or selected from halogen, C ₁To C₆Alkyl, OR_10aAnd NR_10bR_10cSubstituted with one or more groups of (a)), an epoxy group, a cycloalkyl ring system (said cycloalkyl ring system being unsubstituted or selected from halogen, C₁To C₆Alkyl, OR_10dAnd NR_10eR_8fSubstituted with one OR more groups of (a), OR_10g、Si(OR_10h)₃、NR_10iR_10jAnd N⁺R_10kR_10lR_10m；

R_8hand R_10hEach independently represents C₁To C₃Alkyl radicalAnd (4) clustering.

30. The degradable polymeric material of clause 29, wherein when present, Y is selected from:

CN；

C₁to C₆An alkyl group which is unsubstituted or substituted by one or more of: halogen, benzene ring (the benzene ring is unsubstituted or selected from halogen, C₁To C₃Alkyl, OR_5aAnd NR_5bR_5cIs substituted with one or more groups), an epoxy group, a cyclohexane ring, a cyclopentane ring (the cyclohexane or cyclopentane ring is unsubstituted or is selected from halogen, C₁To C₃Alkyl, OR_5dAnd NR_5eR_5fSubstituted with one OR more groups of (a), OR_5g、Si(OR_5h)₃、NR_5iR_5jAnd N⁺R_5kR_5lR_5m；

OR_6a；

-C(＝O)OR_6b；

-A-(OLO)_p-R₇；

R_4a、R_5aTo R_5gAnd R_5iTo R_5lEach independently represents H or C₁To C₆An alkyl group;

each R_5hIndependently represent C₁To C₆An alkyl group;

R_6aand R_6bEach independently represents:

H；

C₁To C₆An alkyl group which is unsubstituted or substituted by one or more of: halogen, aromatic or heteroaromatic ring systems (said aromatic or heteroaromatic ring systems being unsubstituted or selected from halogen, C₁To C₆Alkyl, OR_8aAnd NR_8bR_8cSubstituted with one or more groups), epoxy groups, and epoxy groups,Cycloalkyl ring systems (said cycloalkyl ring systems being unsubstituted or selected from halogen, C₁To C₆Alkyl, OR_8dAnd NR_8eR_8fSubstituted with one OR more groups of (a), OR_8g、Si(OR_8h)₃、NR_8iR_8jAnd N⁺R_8kR_8lR_8m；

a represents a bond or is-C (═ O) -;

l represents an alkyl chain of 2 to 4 carbon atoms;

p has a value of 10 to 250;

R_8aTo R_8g、R_8iTo R_8m、R_9aTo R _9c、R_10aTo R_10g、R_10iTo R_10mEach independently represents H or C₁To C₃An alkyl group;

R_8hand R_10hEach independently represents C₁To C₃An alkyl group.

31. The degradable polymeric material of any of clauses 18 to 30 wherein when n has a non-zero integer valueTime, 2]_mThe repeating units in the degradable polymer material account for 0.01 to 99.99 wt%.

32. The degradable polymeric material of clause 31, wherein when n has a non-zero integer value, [ 2 ]]_mThe repeating units in (b) constitute 0.05 to 50 wt%, such as 0.1 to 30 wt%, such as 0.5 to 10 wt%, such as 1 to 5 wt% of the degradable polymeric material.

33. The degradable polymeric material of any of clauses 18-32 wherein the degradable polymeric material has a number average molecular weight (M)_n) From 200 to 10,000,000 daltons, such as from 500 to 5,000,000 daltons, such as from 1,000 to 1,000,000 daltons.

34. The degradable polymeric material of any of clauses 18-33 wherein the degradable polymeric material has a number average molecular weight (M)_n) From 500 to 200,000 daltons, such as from 2,000 to 100,000 daltons.

35. A method of forming a degradable polymeric material according to any one of clauses 1 to 17, the method comprising the steps of, mixing:

A repeat unit of the formula I or formula II as defined in any one of clauses 1 to 17]_mA first monomer precursor of (a); and

when n has a non-zero integer value, corresponds to the repeating unit of formula I or formula II as defined in any one of clauses 1 to 17]_nA second monomer precursor of (2), with

One or more of an initiator compound, a free radical initiator, a catalyst, and a solvent, and allowing the polymerization reaction to proceed for a period of time to provide the degradable polymeric material of any of clauses 1-17.

36. A method of forming the degradable polymeric material of any one of clauses 18-34, the method comprising the steps of, mixing:

a recurring unit of the formula III or IV as defined in any of the clauses 18 to 34]_mA first monomer precursor of (a); and

when n has a non-zero integer value, corresponding to clauses 18 to 34The repeating unit of the formula III or the formula IV defined in any one of the above]_nA second monomer precursor of (2), with

One or more of an initiator compound, a free radical initiator, a catalyst, and a solvent, and allowing the polymerization reaction to proceed for a period of time to provide the degradable polymeric material of any of clauses 18-34.

Drawings

Fig. 1 depicts: (a) the structure of Cyclic Ketene Diheterolone (CKDHO) monomer used for synthesizing the degradable polymer of the present invention; and (b) schematic representation of polymer synthesis and degradation.

Fig. 2 depicts: (a) schematic representation of existing CKA polymerization techniques; and (b) schematic representation of the polymerization of 5-and 7-membered CKDOOs, respectively, to form the degradable polymers of the invention.

Fig. 3 depicts the structures of monomers, initiators, free radical initiators, and catalysts used to synthesize the degradable polymers of the present invention.

FIG. 4 depicts: (a) of PDMDL (Table 1, entry 1) of the present invention¹H NMR spectrum; and (b)¹³C NMR spectrum.

FIG. 5 depicts: (a) of PMMA-r-PDMDL (Table 1, entry 3) of the present invention¹H NMR spectrum; and (b)¹³C NMR spectrum.

FIG. 6 depicts: (a) of PMMA-r-PPhDL (Table 2, entry 2) of the present invention¹H NMR spectrum; and (b)¹³C NMR spectrum.

FIG. 7 depicts: of PDMDL after alkaline hydrolytic degradation¹H NMR spectrum; and (b)¹³C NMR spectrum.

Figure 8 depicts a possible degradation mechanism for the environmentally friendly leave-on structure obtained from CKDOO.

Figure 9 depicts a possible mechanism for the degradation of the PDMDL backbone under alkaline conditions.

FIG. 10 depicts PMMA-r-PDMDL (with 21% DMDL fraction, M) before and after degradation (5min, 1h and 24h) _n＝17900g/mol，

) GPC color ofSpectra.

Fig. 11 depicts the following GPC chromatograms: before (0h) and after (24h) hydrolytic degradation, (a) PPEGMA-r-PDMDL (with 10% DMDL fraction, M)_n＝16500g/mol，

) (ii) a And (b) PPEGMA.

Detailed Description

In a first aspect of the invention, a degradable polymeric material is disclosed, comprising a polymer of formula I:

wherein:

m has a non-zero integer value;

n has a value of 0 or a non-zero integer value;

X₁and X₂Independently selected from O, NR_aOr S;

R_ais H or C₁To C₆An alkyl group;

when present, R₃Is H or C₁To C₆An alkyl group;

when present, Y is selected from:

CN；

C₁to C₂₀An alkyl group which is unsubstituted or substituted by one or more of: halogen, aromatic or heteroaromatic ring systems(the aromatic or heteroaromatic ring system being unsubstituted or selected from halogen, C₁To C₆Alkyl, OR _5aAnd NR_5bR_5cSubstituted with one or more groups of (a)), an epoxy group, a cycloalkyl ring system (said cycloalkyl ring system being unsubstituted or selected from halogen, C₁To C₆Alkyl, OR_5dAnd NR_5eR_5fSubstituted with one OR more groups of (a), OR_5g、Si(OR_5h)₃、NR_5iR_5jAnd N⁺R_5kR_5lR_5m；

OR_6a；

-C(＝O)OR_6b；

-A-(OLO)_p-R₇；

each R_5hIndependently represent C₁To C₆An alkyl group;

R_6aand R_6bEach independently represents:

H；

C₁to C₂₀An alkyl group which is unsubstituted or substituted by one or more of: halogen, aromatic or heteroaromatic ring systems (said aromatic or heteroaromatic ring systems being unsubstituted or selected from halogen, C₁To C₆Alkyl, OR_8aAnd NR_8bR_8cSubstituted with one or more groups of (a)), an epoxy group, a cycloalkyl ring system (said cycloalkyl ring system being unsubstituted or selected from halogen, C₁To C₆Alkyl, OR_8dAnd NR_8eR_8fSubstituted with one OR more groups of (a), OR_8g、Si(OR_8h)₃、NR_8iR_8jAnd N⁺R_8kR_8lR_8m；

a represents a bond or is-C (═ O) -;

l represents an alkyl chain of 2 to 10 carbon atoms;

p has a value of 1 to 1000;

R₇is represented by C₁To C₂₀An alkyl group which is unsubstituted or substituted by one or more of: halogen, aromatic or heteroaromatic ring systems (said aromatic or heteroaromatic ring systems being unsubstituted or selected from halogen, C ₁To C₆Alkyl, OR_10aAnd NR_10bR_10cSubstituted with one or more groups of (a)), an epoxy group, a cycloalkyl ring system (said cycloalkyl ring system being unsubstituted or selected from halogen, C₁To C₆Alkyl, OR_10dAnd NR_10eR_8fSubstituted with one OR more groups of (a), OR_10g、Si(OR_10h)₃、NR_10iR_10jAnd N⁺R_10kR_10lR_10m；

and salts or solvates thereof.

In certain embodiments, the polymeric material described herein can be a mixture of a ring-closing polymer (i.e., formula I above) and a ring-opening polymer (i.e., formula II below). In certain embodiments, the polymeric material may be formed substantially from a ring-opened polymer of formula II (i.e., the amount of ring-closed polymer of formula I is lower than that used below)¹³Limit of detection of C NMR apparatus). In yet further embodiments, the polymer chain may comprise repeating units of the polymers according to formula I and formula II. However, in embodiments of the invention that may be mentioned herein, the polymeric material may consist essentially of a ring-closed polymer of formula IAnd (4) forming. That is, the polymer of formula I can comprise greater than or equal to 90 wt%, such as greater than or equal to 95 wt%, such as greater than or equal to 99 wt%, such as greater than or equal to 99.99999 wt% of the polymeric material. For example, the polymeric material may be formed from a polymer of formula I and the amount of ring-opened polymer of formula II may be lower than that used herein ¹³Detection limit of CNMR devices.

Thus, in aspects and embodiments of the invention that may be mentioned herein, the polymeric material may be or may further comprise a polymer of formula II:

wherein, X₁、X₂、m、n、R₁To R₃And the value of Y is as defined above.

As referred to herein, R₁And R₂(or R)₁₁To R₁₆Formulas III and IV) described below may be independently selected from halogen, alkyl groups, aromatic groups, heteroaromatic groups, ether groups, ester groups, ketone groups, hydroxyl groups, carboxylic acid groups, or amine groups.

In which R is₁And/or R₂(or R)₁₁To R₁₆One or more of) is an alkyl group, the alkyl group may be unsubstituted or substituted with one or more halogen atoms. In an embodiment of the invention, when R₁And/or R₂(or R)₁₁To R₁₆One or more of) is an alkyl group, the alkyl group may be linear or branched and may have 1 to 6 carbon atoms which are unsubstituted or substituted with one or more halogen atoms.

In which R is₁And/or R₂(or R)₁₁To R₁₆One or more of) is an aromatic group, the aromatic group may be C₆To C₁₄(such as C)₆To C₁₀) An aromatic group. Such groups may be monocyclic, bicyclic or tricyclic and have 6 to 14 Ring carbon atoms, at least one of which is aromatic. The point of attachment of the aryl group may be through any atom of the ring system. However, when the aryl groups are bicyclic or tricyclic, they are attached to the rest of the molecule through an aromatic ring. C₆To C₁₄Aromatic groups include phenyl, naphthyl, and the like, such as 1,2,3, 4-tetrahydronaphthyl, indanyl, indenyl, and fluorenyl. Embodiments of the invention that may be mentioned include those in which the aryl group is phenyl. The aromatic groups mentioned herein may be unsubstituted or substituted by one or more groups selected from: halogen, C₁To C₆Alkyl, heteroaromatic radical (which may be referred to as R below)₁And/or R₂(or R)₁₁To R₁₆One or more) of heteroaromatic groups as defined above), O-C₁To C₆Alkyl, -O (C ═ O) -C₁To C₆Alkyl, -C (═ O) O-C₁To C₆Alkyl, ═ O, OH, CO₂H and NR_xR_x’Wherein R is_xAnd R_x’Is H or C₁To C₆An alkyl group. The alkyl-containing substituents on the aromatic group may be unsubstituted or substituted with one or more halogen atoms.

In which R is₁And/or R₂(or R)₁₁To R₁₆One or more of) is a heteroaromatic group, the heteroaromatic group may be a 5 to 14 or 3 to 10 membered heterocyclic group, which may be monocyclic, bicyclic or tricyclic, respectively, wherein at least one ring has aromatic character. The heteroaromatic group may contain up to 5 heteroatom ring members selected from O, N and S, and more particularly up to 4 heteroatom ring members. For example, a heteroaromatic group may contain 1,2 or 3 heteroatom ring members. Examples of heteroaromatic groups that may be mentioned herein include, but are not limited to, aza rings

Radical (azepinyl), diaza

Alkyl, furyl, furazanyl, imidazolyl, isofurylThiazolyl, isoxazolidinyl, isoxazolyl, oxadiazolyl, pyrazolyl, pyridyl, pyrimidinyl, tetrazolyl, thiadiazolyl, thiazolyl, thienyl, thioethoxyphenyl (thiophenylenyl), triazolyl, isobenzofuranyl, pyrazinyl, pyrazolyl, pyridazinyl, triazinylalkyl (triazonanyl), and the like. The point of attachment of the carbocyclic group may be through any atom of the ring system. The heteroaromatic groups mentioned herein may be unsubstituted or substituted by one or more groups selected from: halogen, C₁To C₆Alkyl, heteroaromatic groups (as defined above, but unsubstituted or substituted only by one or more halogen atoms), O-C₁To C₆Alkyl, -O (C ═ O) -C₁To C₆Alkyl, -C (═ O) O-C₁To C₆Alkyl, ═ O, OH, CO₂H and NR_xR_x’Wherein R is_xAnd R_x’Is H or C₁To C₆An alkyl group. The alkyl-containing substituents on the heteroaromatic groups may be unsubstituted or substituted with one or more halogen atoms.

In which R is₁And/or R₂(or R)₁₁To R₁₆One OR more of) is an ether group, the ether group may be OR_x", wherein R _x"may represent a straight chain or branched C₁To C₆An alkyl chain which is unsubstituted or substituted by one or more groups selected from: halogen, heteroaromatic radical (which may be as above referred to R)₁And/or R₂(or R)₁₁To R₁₆One or more) of heteroaromatic groups as defined above), O-C₁To C₆Alkyl, -O (C ═ O) -C₁To C₆Alkyl, -C (═ O) O-C₁To C₆Alkyl, ═ O, OH, CO₂H and NR_xR_x’Wherein R is_xAnd R_x’Is H or C₁To C₆An alkyl group. The alkyl-containing substituents on the ether groups may be unsubstituted or substituted with one or more halogen atoms.

In which R is₁And/or R₂(or R)₁₁To R₁₆One or more of) In embodiments of the invention that are ester groups, the ester group may be-O (C ═ O) -C₁To C₆Alkyl or-C (═ O) O-C₁To C₆An alkyl group. The alkyl group may be unsubstituted or substituted with one or more halogen atoms.

In which R is₁And/or R₂(or R)₁₁To R₁₆One or more of) is an amine group, the amine group may be NR in embodiments of the invention_xR_x', wherein R_xAnd R_x' is H or C₁To C₆An alkyl group. The alkyl group may be unsubstituted or substituted with one or more halogen atoms.

The word "comprising" in this context may be interpreted as requiring the presence of the stated features, but does not limit the presence of other features. Alternatively, the word "comprising" may also refer to instances where only the listed components/features are intended to be present (e.g., the word "comprising" may be replaced by the phrase "consisting of … …" or "consisting essentially of … …"). It is expressly contemplated that either a broad or narrow interpretation may apply to all aspects and embodiments of the invention. In other words, the word "comprising" and its synonyms may be replaced by the phrase "consisting of … …" or the phrase "consisting essentially of … …" or its synonyms, and vice versa.

As used herein, the term "halogen" includes references to fluorine, chlorine, bromine and iodine.

As will be noted, the polymers of formulae I, II, III, and IV disclosed herein may include ammonium groups. In this case, a counter ion may be present, providing a salt of the compound. Suitable counterions include, but are not limited to, halide ions (e.g., F)^-、Cl^-、Br^-、I^-)。

Furthermore, the polymeric materials mentioned herein may be provided in salt form by reacting the polymer with an acid or base to provide acid addition salts and base addition salts. Such salts may be formed by conventional means, for example by reacting the free acid or free base form of a compound of formula I, II, III or IV with one or more equivalents of the appropriate acid or base, optionally in a solvent or medium in which the salt is insoluble, followed by removal of the solvent or medium using standard techniques (e.g. by lyophilization or filtration in vacuo). Salts may also be prepared by: the counter ion of the compound of formula I, II, III or IV in the form of a salt is exchanged with another counter ion, for example using a suitable ion exchange resin.

Examples of suitable salts include acid addition salts derived from mineral and organic acids, as well as salts derived from metals such as sodium, magnesium, or preferably potassium and calcium.

Examples of acid addition salts include the acid addition salts formed with: acetic acid, 2-dichloroacetic acid, adipic acid, alginic acid, arylsulfonic acids (e.g., benzenesulfonic acid, naphthalene-2-sulfonic acid, naphthalene-1, 5-disulfonic acid, and p-toluenesulfonic acid), ascorbic acid (e.g., L-ascorbic acid), L-aspartic acid, benzoic acid, 4-acetamidobenzoic acid, butyric acid, (+) camphoric acid, camphor-sulfonic acid, (+) - (1S) -camphor-10-sulfonic acid, capric acid, caproic acid, caprylic acid, cinnamic acid, citric acid, cyclamic acid, dodecylsulfuric acid, ethane-1, 2-disulfonic acid, ethanesulfonic acid, 2-hydroxyethanesulfonic acid, formic acid, fumaric acid, galactaric acid, gentisic acid, glucoheptonic acid, gluconic acid (e.g., D-gluconic acid), glucuronic acid (e.g., d-glucuronic acid), glutamic acid (e.g., L-glutamic acid), α -oxoglutaric acid, glycolic acid, hippuric acid, hydrobromic acid, hydrochloric acid, hydroiodic acid, isethionic acid, lactic acid (e.g., (+) -L-lactic acid and (±) -DL-lactic acid), lactobionic acid, maleic acid, malic acid (e.g., (-) -L-malic acid), malonic acid, (±) -DL-mandelic acid, metaphosphoric acid, methanesulfonic acid, 1-hydroxy-2-naphthoic acid, nicotinic acid, nitric acid, oleic acid, orotic acid, oxalic acid, palmitic acid, pamoic acid, phosphoric acid, propionic acid, L-pyroglutamic acid, salicylic acid, 4-amino-salicylic acid, sebacic acid, stearic acid, succinic acid, sulfuric acid, tannic acid, tartaric acid (e.g., (+) -L-tartaric acid), Thiocyanic acid, undecylenic acid, and valeric acid.

Specific examples of salts are those derived from: mineral acids such as hydrochloric acid, hydrobromic acid, phosphoric acid, metaphosphoric acid, nitric acid and sulfuric acid; organic acids such as tartaric acid, acetic acid, citric acid, malic acid, lactic acid, fumaric acid, benzoic acid, glycolic acid, gluconic acid, succinic acid, arylsulfonic acids; and metals such as sodium, magnesium, or preferably potassium and calcium.

The polymers of formulae I, II, III and IV also include any solvates of the compounds and salts thereof. Preferred solvates are those formed by incorporating molecules of a solvent (hereinafter referred to as a solvating solvent) into the solid state structure (e.g., crystal structure) of the compounds of the present invention. Examples of such solvents include water, alcohols (such as ethanol, isopropanol, and butanol), and dimethyl sulfoxide. Solvates may be prepared by recrystallisation of the compounds of the invention from a solvent or a mixture of solvents comprising solvating solvents. Whether a solvate has been formed, in any given case, can be determined by subjecting crystals of the compound to analysis using well-known and standard techniques, such as thermogravimetric analysis (TGA), Differential Scanning Calorimetry (DSC), and X-ray crystallography.

The solvate may be a stoichiometric or non-stoichiometric solvate. Particularly preferred solvates are hydrates, and examples of hydrates include hemihydrate, monohydrate, and dihydrate.

For a more detailed discussion of solvates and methods for making and characterizing them, see Bryn et al, Solid-State Chemistry of Drugs, Second Edition, published by SSCI, Inc of West Lafayette, IN, USA,1999, ISBN 0-967-.

In an embodiment of the invention relating to polymers of the formula I and/or II, X₁And X₂May be O and X₁And X₂May be independently selected from O, NR_aOr S. For example, in the embodiments of the invention that may be mentioned herein, X₁And X₂Both may be O.

In an embodiment of the invention relating to polymers of formula I and/or formula II, R₁And R₂May be independently selected from alkyl groups and aromatic groups. For example, R₁And R₂Can be independently selected from C₁To C₃Alkyl groups and phenyl groups. In the detailed implementation of the inventionIn the formula, R₁And R₂Both of which may be methyl groups, or R₁May be a methyl group and R₂May be a phenyl group. Unless otherwise specified, the alkyl groups referred to in this paragraph may be unsubstituted or substituted with one or more halogen atoms. Unless otherwise indicated, the aromatic groups mentioned in this paragraph may employ those set forth above with respect to R ₁And/or R₂(or R)₁₁To R₁₆One or more) of (a) or (b) is provided.

When n in the polymer of the formula I and/or the formula II is 0, the polymer of the formula I and the polymer of the formula II do not comprise "[ 2 ]]_n' the repeating unit contained in (1). However, in particular embodiments of the present invention, n may have a non-zero integer value. In the latter embodiment, the polymer of formula I and the polymer of formula II will be a copolymer material. In this case, the polymer of formula I and the polymer of formula II may each be a random copolymer or a block copolymer, or the polymer chains may share the characteristics of both. For example, when used to form polymers of formula I and formula II]_nWhen the amount of the monomer of the repeating unit represented is provided in a significant excess, the monomer material may be more than that used to form the repeating unit [ 2 ]]_mThe monomer of (A) is more easily reacted, and thus the [ 2 ] can be produced]_nBlocks of repeating units, which blocks may be substituted by the repeating unit [ 2 ]]_mAnd (4) randomly interrupting. However, as the polymerization proceeds toward completion, it is used to form the repeating unit [ 2 ]]_nWill be significantly reduced, and thus the polymer chain may then comprise monomer units therein]_mAnd 2]_nMore equally represented areas. Finally, as the polymerization reaction approaches its end, it is used to form the repeating unit [ 2 ] ]_mThe monomer (2) can now be used in a ratio to form the repeating unit [ 2 ]]_nIs present in a significantly higher concentration and thus the polymer chain may also thus comprise]_nThe repeating unit being randomly interrupted [ 2 ]]_mA block of repeating units.

In embodiments of the invention where n has a non-zero integer value, the recurring unit of formula Ia in formula I or formula II:

may be formed of one or more monomers selected from the group consisting of styrene, acrylate, methacrylate, acrylamide and methacrylamide. For example, a repeat unit of formula Ia in formula I or formula II:

may be formed from monomers selected from one or more of the group consisting of: acrylonitrile, styrene, methoxystyrene, butoxystyrene, chloromethylstyrene, chlorostyrene, methyl acrylate, ethyl acrylate, propyl acrylate, n-butyl acrylate, t-butyl acrylate, hexyl acrylate, 2-ethylhexyl acrylate, n-octyl acrylate, nonyl acrylate, decyl acrylate, benzyl acrylate, tetrahydrofurfuryl acrylate, glycidyl acrylate, cyclohexyl acrylate, 2-methoxyethyl acrylate and butoxyethyl acrylate, tris (trialkylsiloxy) derivative-acrylic acid ester and fluoroalkyl acrylate, methyl methacrylate, ethyl methacrylate, propyl methacrylate, n-butyl methacrylate, t-butyl methacrylate, hexyl methacrylate, 2-ethylhexyl methacrylate, n-octyl methacrylate, n-butyl acrylate, or a, Nonyl methacrylate, decyl methacrylate, benzyl methacrylate, tetrahydrofurfuryl methacrylate, glycidyl methacrylate, cyclohexyl methacrylate, 2-methoxyethyl methacrylate, butoxyethyl methacrylate, tris (trialkylsiloxy) derivative-methacrylate, fluoroalkyl methacrylate, hydroxystyrene, styrenesulfonic acid, sodium styrenesulfonate, styreneboric acid, acrylamide, N-isopropylacrylamide, N-dimethylacrylamide, N-methylolacrylamide, N-hydroxyethylacrylamide, methacrylamide, N-isopropylacrylamide, N-dimethylmethacrylamide, N-methylolmethacrylamide, N-hydroxyethylmethacrylamide, N-methylolmethacrylamide Methacrylamide, acrylic acid, hydroxyalkyl acrylates (e.g.2-hydroxyethyl acrylate), 2-hydroxypropyl acrylate, glycerol monoacrylate, diethylene glycol acrylate, polyethylene glycol acrylate, methoxy tetraethylene glycol acrylate, methoxy polyethylene glycol acrylate, 2- (dimethylamino) ethyl acrylate, 3-chloro-2-hydroxypropyl acrylate, 2-hydroxy-3-phenoxypropyl acrylate, 2-acryloxyethyl phosphorylcholine, 2- (N, N-diethyl-N-methylamino) ethyl +/trifluorosulfonyliminium salt, 2- (N-ethyl-N-methyl-N-hydroamino) ethyl acrylate +/trifluorosulfonyliminium (N (CF).₃SO₂)^2-) Salt, 1-ethyl-3-methylimidazolium acrylate +/fluorohydrogenate ((FH) nF)^-) Salts, methacrylic acid, 2-hydroxyethyl methacrylate, 2-hydroxypropyl methacrylate, glycerol monomethacrylate, diethylene glycol methacrylate and polyethylene glycol methacrylate, methoxy tetraethylene glycol methacrylate, methoxy polyethylene glycol methacrylate, 2- (dimethylamino) ethyl methacrylate, 3-chloro-2-hydroxypropyl methacrylate, 2-hydroxy-3-phenoxypropyl methacrylate, 2-acryloxyethylphosphorylcholine, 2- (N, N-diethyl-N-methylamino) ethyl ester +/trifluorosulfonyliminium salt, 2- (N-ethyl-N-methyl-N-hydroamino) ethyl methacrylate +/trifluorosulfonyliminium (N (CF). ₃SO₂)^2-) Salt and 1-ethyl-3-methylimidazolium methacrylate +/fluorohydrogenate ((FH) nF)^-) And (3) salt.

In a particular embodiment of the invention, the recurring unit of formula Ia in formula I or formula II:

may be formed from monomers selected from one or more of the group consisting of: methyl Methacrylate (MMA), Butyl Acrylate (BA) (e.g., n-butyl acrylate), Acrylonitrile (AN), poly (ethylene glycol) methyl ether methacrylate (PEGMA), Butyl Methacrylate (BMA) (e.g., n-butyl methacrylate), styrene (St), and 2-methoxyethyl acrylate (MEA).

In an embodiment of the invention relating to polymers of formula I and/or formula II, R when n has a non-zero integer value₃May be H or C₁To C₃An alkyl group. For example, R₃May be H or methyl. Unless otherwise specified, the alkyl groups referred to in this paragraph may be unsubstituted or substituted with one or more halogen atoms.

In yet further embodiments of the present invention directed to polymers of formula I and/or formula II, Y may be selected from:

CN；

OR_6a；

-C(＝O)OR_6b；

-A-(OLO)_p-R₇；

each R_5hIndependently represent C₁To C₆An alkyl group;

R_6aand R_6bEach independently represents:

H；

C₁to C₁₀An alkyl group which is unsubstituted or substituted by one or more of: halogen, aromatic or heteroaromatic ring systems (said aromatic or heteroaromatic ring systems being unsubstituted or selected from halogen, C₁To C₆Alkyl, OR_8aAnd NR_8bR_8cSubstituted with one or more groups of (a)), an epoxy group, a cycloalkyl ring system (said cycloalkyl ring system being unsubstituted or selected from halogen, C₁To C₆Alkyl, OR_8dAnd NR_8eR_8fSubstituted with one OR more groups of (a), OR_8g、Si(OR_8h)₃、NR_8iR_8jAnd N⁺R_8kR_8lR_8m；

a represents a bond or is-C (═ O) -;

l represents an alkyl chain of 2 to 4 carbon atoms;

p has a value of 5 to 500;

R_8hand R_10hEach independently represents C₁To C₃An alkyl group. For example, Y may be selected from:

CN；

OR_6a；

-C(＝O)OR_6b；

-A-(OLO)_p-R₇；

each R_5hIndependently represent C₁To C₆An alkyl group;

R_6aand R_6bEach independently represents:

H；

C₁to C₆An alkyl group which is unsubstituted or substituted by one or more of: halogen, aromatic or heteroaromatic ring systems (said aromatic or heteroaromatic ring systems being unsubstituted or selected from halogen, C ₁To C₆Alkyl, OR_8aAnd NR_8bR_8cSubstituted with one or more groups of (a)), an epoxy group, a cycloalkyl ring system (said cycloalkyl ring system being unsubstituted or selected from halogen, C₁To C₆Alkyl, OR_8dAnd NR_8eR_8fSubstituted with one OR more groups of (a), OR_8g、Si(OR_8h)₃、NR_8iR_8jAnd N⁺R_8kR_8lR_8m；

a represents a bond or is-C (═ O) -;

l represents an alkyl chain of 2 to 4 carbon atoms;

p has a value of 10 to 250;

R_8hand R_10hEach independently represents C₁To C₃An alkyl group.

In an embodiment of the invention relating to polymers of formula I and/or formula II, when n has a non-zero integer value, or ]_mThe internal repeating units may comprise 0.01 to 99.99 mol% (in the polymer of formula I or formula II) of the degradable polymeric material. For example, when n has a non-zero integer value, [ 2 ]]_mThe repeat units within may comprise 0.05 to 50 mol%, such as 0.1 to 30 mol%, such as 0.5 to 10 mol%, such as 1 to 5 mol% of the degradable polymeric material.

In embodiments of the invention involving polymers of formula I and/or formula II, the degradable polymeric material can have any suitable number average molecular weight (M)_n). Suitable M for degradable polymeric materials that may be mentioned herein_nIncluding M of 150 to 10,000,000 daltons, such as 500 to 5,000,000 daltons, such as 1,000 to 1,000,000 daltons, such as 500 to 200,000 daltons, such as 2,000 to 100,000 daltons_n. For the avoidance of doubt, where a plurality of numerical ranges relating to the same feature are expressly contemplated herein, the endpoints of each range are intended to be combined in any order to provide the further contemplated (and implicitly disclosed) range. Accordingly, with respect to the above-described relevant numerical ranges, the following M is disclosed_n：

150 to 500 daltons, 150 to 1,000 daltons, 150 to 2,000 daltons, 150 to 100,000 daltons, 150 to 200,000 daltons, 150 to 1,000,000 daltons, 150 to 5,000,000 daltons, 150 to 10,000,000 daltons;

500 to 1,000 daltons, 500 to 2,000 daltons, 500 to 100,000 daltons, 500 to 200,000 daltons, 500 to 1,000,000 daltons, 500 to 5,000,000 daltons, 500 to 10,000,000 daltons;

1,000 to 2,000 daltons, 1,000 to 100,000 daltons, 1,000 to 200,000 daltons, 1,000 to 1,000,000 daltons, 1,000 to 5,000,000 daltons, 1,000 to 10,000,000 daltons;

2,000 to 100,000 daltons, 2,000 to 200,000 daltons, 2,000 to 1,000,000 daltons, 2,000 to 5,000,000 daltons, 2,000 to 10,000,000 daltons;

100,000 to 200,000 daltons, 100,000 to 1,000,000 daltons, 100,000 to 5,000,000 daltons, 100,000 to 10,000,000 daltons;

200,000 to 1,000,000 daltons, 200,000 to 5,000,000 daltons, 200,000 to 10,000,000 daltons;

1,000,000 to 5,000,000 daltons, 1,000,000 to 10,000,000 daltons; and

5,000,000 to 10,000,000 daltons.

As will be appreciated, the present invention also relates to a method of manufacturing the above degradable polymeric material. Accordingly, there is also disclosed a method of forming a degradable polymeric material as described above, the method comprising the steps of, mixing:

Corresponding to the repeat unit in formula I or formula II as defined herein]_mA first monomer precursor of (a); and

when n has a non-zero integer value, corresponds to the repeating unit [ 2 ] in formula I or formula II as defined herein]_nA second monomer precursor of (2), with

One or more of an initiator compound, a free radical initiator, a catalyst and a solvent, and allowing the polymerization reaction to proceed for a period of time to provide a degradable polymeric material as defined herein.

Any suitable catalyst may be used in the process of forming the polymeric material disclosed herein (i.e., a polymeric material comprising a polymer of formula I and/or formula II or a polymeric material comprising a polymer of formula III and/or formula IV). For example, the catalyst may be, but is not limited to, tetrabutylammonium iodide.

Any suitable initiator compound may be used in the process of forming the polymeric materials disclosed herein (i.e., polymeric materials comprising polymers of formula I and/or formula II or polymeric materials comprising polymers of formula II and/or formula IV). For example, the initiator compound may be, but is not limited to, 2-methylpropanenitrile.

Any suitable free radical initiator may be used in the process of forming the polymeric materials disclosed herein (i.e., polymeric materials comprising polymers of formula I and/or formula II or polymeric materials comprising polymers of formula II and/or formula IV). Examples of suitable free radical initiators include, but are not limited to, 2 '-azobis (2, 4-dimethylvaleronitrile), 2' -azobis (2-methylpropanenitrile), and tert-butyl peroxybenzoate.

Any suitable solvent can be used in the method of forming the polymeric material disclosed herein (i.e., the polymeric material comprising the polymer of formula I and/or formula II or the polymeric material comprising the polymer of formula II and/or formula IV). Examples of such solvents include, but are not limited to, glycols, toluene, and ethylene carbonate. As will be appreciated, the above disclosed process may not require any solvent.

In a further aspect of the invention, a degradable polymeric material is disclosed, comprising a polymer of formula III:

wherein:

m has a non-zero integer value;

n has a value of 0 or a non-zero integer value;

X₁and X₂Independently selected from O, NR_aOr S;

R_ais H or C₁To C₆An alkyl group;

when present, R₃Is H or C₁To C₆An alkyl group;

when present, Y is selected from:

an aromatic or heteroaromatic ring system which is unsubstituted or selected from halogen, C ₁To C₆Alkyl, OR_4a、NR_4bR_4c、SO₃H and B (OH)₂Substituted with one or more groups of (a);

CN；

OR_6a；

-C(＝O)OR_6b；

-A-(OLO)_p-R₇；

each R_5hIndependently represent C₁To C₆An alkyl group;

R_6aand R_6bEach independently represents:

H；

C₁to C₂₀An alkyl group which is unsubstituted or substituted by one or more of: halogen, aromatic or heteroaromatic ring systems (said aromatic or heteroaromatic ring systems being unsubstituted or selected from halogen, C₁To C₆Alkyl, OR_8aAnd NR_8bR_8cSubstituted with one or more groups of (a), a ringOxygen radicals, cycloalkyl ring systems (said cycloalkyl ring systems being unsubstituted or selected from halogen, C₁To C₆Alkyl, OR_8dAnd NR_8eR_8fSubstituted with one OR more groups of (a), OR_8g、Si(OR_8h)₃、NR_8iR_8jAnd N⁺R_8kR_8lR_8m；

Cycloalkyl ring systems (said cycloalkyl ring systems being unsubstituted or selected from halogen, C ₁To C₆Alkyl, OR_9aAnd NR_9bR_9cSubstituted with one or more groups of (a);

a represents a bond or is-C (═ O) -;

l represents an alkyl chain of 2 to 10 carbon atoms;

p has a value of 1 to 1000;

and salts or solvates thereof.

Unless otherwise indicated, the definitions provided for the polymers of formulae I and II also apply to the polymers of formulae III and IV. For example, the definitions of halogen, salts and solvates as described for polymers formula I and II also apply to the polymers of formula III and IV.

In certain embodiments, the polymeric material described herein can be a mixture of a ring-closing polymer (i.e., formula III above) and a ring-opening polymer (i.e., formula IV below). In certain embodiments, the polymeric material may be formed substantially from the ring-opened polymer of formula IV (i.e., the amount of ring-closed polymer of formula III is lower than that used below) ¹³Limit of detection of C NMR apparatus). In yet further embodiments, the polymer chain may comprise repeating units of the polymers according to formula III and formula IV. However, in embodiments of the invention that may be mentioned herein, the polymeric material may be formed substantially from a ring-closing polymer of formula III. That is, the polymer of formula III can comprise greater than or equal to 90 wt%, such as greater than or equal to 95 wt%, such as greater than or equal to 99 wt%, such as greater than or equal to 99.99999 wt% of the polymeric material. For example, the polymeric material may be formed from a polymer of formula III and the amount of ring-opened polymer of formula IV may be lower than that used herein¹³Limit of detection of C NMR equipment.

Thus, in aspects and embodiments of the invention that may be mentioned herein, the polymeric material may be or may further comprise a polymer of formula IV:

wherein, X₁、X₂、m、n、R₃、R₁₁To R₁₆And the value of Y is as defined above for formula III.

In an embodiment of the invention relating to polymers of the formula III and/or IV, X₁And X₂May be O and X₁And X₂May be independently selected from O, NR_aOr S. For example, in the embodiments of the invention that may be mentioned herein, X₁And X₂Both may be O.

In an embodiment of the invention relating to polymers of formula III and/or formula IV, R₁₁To R₁₆May be independently selected from H, alkyl groups and aromatic groups, or R₁₃To R₁₆Together with the carbon atoms to which they are attached may form an unsubstituted benzene ring. For example, R₁₁To R₁₆Can be independently selected from H, C₁To C₃Alkyl radicals and phenyl radicals, or R₁₃To R₁₆Together with the carbon atoms to which they are attached may form an unsubstituted benzene ring. Unless otherwise specified, the alkyl groups referred to in this paragraph may be unsubstituted or substituted with one or more halogen atoms. Unless otherwise indicated, the aromatic groups mentioned in this paragraph may employ those set forth above with respect to R₁₁To R₁₆The aromatic group of one or more of (a) or (b) provides the definition.

When n is 0, the polymer of the formula III and the polymer of the formula IV do not contain "[ solution ],]_n' the repeating unit contained in (1). However, in particular embodiments of the present invention, n may have a non-zero integer value. In the latter embodiment, the polymer of formula III and the polymer of formula IV will be a copolymer material. In this case, the polymer of formula III and the polymer of formula IV may each be a random copolymer or a block copolymer, or the polymer chains may share the characteristics of both. For example, when used to form polymers of formula III and formula IV ]_nWhen the amount of the monomer of the repeating unit represented is provided in a significant excess, the monomer material may be more than that used to form the repeating unit [ 2 ]]_mThe monomer of (A) is more easily reacted, and thus the [ 2 ] can be produced]_nBlocks of repeating units, which blocks may be substituted by the repeating unit [ 2 ]]_mAnd (4) randomly interrupting. However, as the polymerization proceeds toward completion, it is used to form the repeating unit [ 2 ]]_nWill be significantly reduced, and thus the polymer chain may then comprise monomer units therein]_mAnd 2]_nMore equally represented areas. Finally, as the polymerization reaction approaches its end, it is used to form the repeating unit [ 2 ]]_mThe monomer (2) can now be used in a ratio to form the repeating unit [ 2 ]]_nAre present in significantly higher concentrations and are therefore polymerizedThe chain of matter may thus also comprise a chain of]_nThe repeating unit being randomly interrupted [ 2 ]]_mA block of repeating units.

In embodiments of the invention where n has a non-zero integer value, the recurring unit of formula Ia in formula III or formula IV:

may be formed of one or more monomers selected from the group consisting of styrene, acrylate, methacrylate, acrylamide and methacrylamide. For example, the repeat unit of formula Ia in formula III or formula IV:

may be formed from monomers selected from one or more of the group consisting of: acrylonitrile, styrene, methoxystyrene, butoxystyrene, chloromethylstyrene, chlorostyrene, methyl acrylate, ethyl acrylate, propyl acrylate, n-butyl acrylate, t-butyl acrylate, hexyl acrylate, 2-ethylhexyl acrylate, n-octyl acrylate, nonyl acrylate, decyl acrylate, benzyl acrylate, tetrahydrofurfuryl acrylate, glycidyl acrylate, cyclohexyl acrylate, 2-methoxyethyl acrylate and butoxyethyl acrylate, tris (trialkylsiloxy) derivative-acrylic acid ester and fluoroalkyl acrylate, methyl methacrylate, ethyl methacrylate, propyl methacrylate, n-butyl methacrylate, t-butyl methacrylate, hexyl methacrylate, 2-ethylhexyl methacrylate, n-octyl methacrylate, n-butyl acrylate, or a, Nonyl methacrylate, decyl methacrylate, benzyl methacrylate, tetrahydrofurfuryl methacrylate, glycidyl methacrylate, cyclohexyl methacrylate, 2-methoxyethyl methacrylate, butoxyethyl methacrylate, tris (trialkylsiloxy) derivative methacrylate, fluoroalkyl methacrylate, hydroxystyrene, styrene Sulfonic acid, sodium styrenesulfonate, styrene boric acid, acrylamide, N-isopropylacrylamide, N-dimethylacrylamide, N-methylolacrylamide, N-hydroxyethylacrylamide, methacrylamide, N-isopropylmethacrylamide, N-dimethylmethacrylamide, N-methylolmethacrylamide, N-hydroxyethyl methacrylamide, acrylic acid, hydroxyalkyl acrylates (e.g., 2-hydroxyethyl acrylate), 2-hydroxypropyl acrylate, glycerol monoacrylate, diethylene glycol acrylate, polyethylene glycol acrylate, methoxytetraethylene glycol acrylate, methoxypolyethylene glycol acrylate, 2- (dimethylamino) ethyl acrylate, 3-chloro-2-hydroxypropyl acrylate, styrene boric acid, acrylamide, N-hydroxyethyl acrylamide, methacrylamide, N-hydroxyethyl methacrylamide, 2-hydroxyethyl methacrylate, glycerol monoacrylate, diethylene glycol acrylate, polyethylene glycol acrylate, methoxytetraethylene glycol acrylate, methoxypolyethylene glycol acrylate, 2- (dimethylamino) ethyl acrylate, 3-chloro-2-hydroxypropyl acrylate, styrene boric acid, ethylene glycol, and mixtures thereof, 2-hydroxy-3-phenoxypropyl acrylate, 2-acryloyloxyethylphosphorylcholine, 2- (N, N-diethyl-N-methylamino) ethyl acrylate +/trifluoromethanesulfonium iminate, 2- (N-ethyl-N-methyl-N-hydroamino) ethyl acrylate +/trifluoromethanesulfonium iminate (N (CF)₃SO₂)^2-) Salt, 1-ethyl-3-methylimidazolium acrylate +/fluorohydrogenate ((FH) nF)^-) Salts, methacrylic acid, 2-hydroxyethyl methacrylate, 2-hydroxypropyl methacrylate, glycerol monomethacrylate, diethylene glycol methacrylate and polyethylene glycol methacrylate, methoxy tetraethylene glycol methacrylate, methoxy polyethylene glycol methacrylate, 2- (dimethylamino) ethyl methacrylate, 3-chloro-2-hydroxypropyl methacrylate, 2-hydroxy-3-phenoxypropyl methacrylate, 2-acryloyloxyethyl phosphorylcholine, 2- (N, N-diethyl-N-methylamino) ethyl ester +/trifluorosulfonyliminium salt, 2- (N-ethyl-N-methyl-N-hydroamino) ethyl methacrylate +/trifluorosulfonyliminium (N (CF). ₃SO₂)^2-) Salt and 1-ethyl-3-methylimidazolium methacrylate +/fluorohydrogenate ((FH) nF)^-) And (3) salt.

In a particular embodiment of the invention, the recurring unit of formula Ia in formula III or formula IV:

In embodiments of the invention involving polymers of formula III and/or formula IV, R when n has a non-zero integer value₃Can be H or C₁To C₃Alkyl radicals, e.g. R₃May be H or methyl. Unless otherwise specified, the alkyl groups referred to in this paragraph may be unsubstituted or substituted with one or more halogen atoms.

In yet further embodiments of the present invention directed to polymers of formula III and/or formula IV, Y may be selected from:

CN；

OR_6a；

-C(＝O)OR_6b；

-A-(OLO)_p-R₇；

each R_5hIndependently represent C₁To C₆An alkyl group;

R_6aand R_6bEach independently represents:

H；

a represents a bond or is-C (═ O) -;

l represents an alkyl chain of 2 to 4 carbon atoms;

p has a value of 5 to 500;

CN；

OR_6a；

-C(＝O)OR_6b；

-A-(OLO)_p-R₇；

each R_5hIndependently represent C₁To C₆An alkyl group;

R_6aand R_6bEach independently represents:

H；

a represents a bond or is-C (═ O) -;

l represents an alkyl chain of 2 to 4 carbon atoms;

p has a value of 10 to 250;

R_8hand R_10hEach independently represents C₁To C₃An alkyl group.

In an embodiment of the invention relating to polymers of formula III and/or formula IV, when n has a non-zero integer value, or ]_mThe repeat units within (b) may comprise 0.01 to 99.99 mol% (in the polymer of formula I or formula II) of the degradable polymeric material. For example, when n has a non-zero integer value, [ 2 ]]_mThe repeat units within may comprise 0.05 to 50 mol%, such as 0.1 to 30 mol%, such as 0.5 to 10 mol%, such as 1 to 5 mol% of the degradable polymeric material.

In embodiments of the invention involving polymers of formula III and/or formula IV, the degradable polymeric material can have any suitable number average molecular weight (M)_n). Suitable M for degradable polymeric materials that may be mentioned herein_nIncluding M of 180 to 10,000,000 daltons, such as 500 to 5,000,000 daltons, such as 1,000 to 1,000,000 daltons, such as 500 to 200,000 daltons, such as 2,000 to 100,000 daltons_n。

As will be appreciated, the present invention also relates to a method of manufacturing the above degradable polymeric material. Accordingly, also disclosed is a method of forming a degradable polymeric material as described herein, the method comprising the steps of, mixing:

corresponding to the repeat unit in formula III or formula IV as defined herein]_mA first monomer precursor of (a); and

when n has a non-zero integer value, corresponds to the repeating unit of formula III or formula IV as defined herein ]_nA second monomer precursor of (2), with

One or more of an initiator compound, a free radical initiator, a catalyst and a solvent, and allowing the polymerization reaction to proceed for a period of time to provide a polymeric material as defined herein.

As will be appreciated, the initiator compound, free radical initiator, catalyst and solvent may be as defined above, and thus will not be repeated here for the sake of brevity.

The polymeric materials described herein may have a variety of applications due to their degradability. As used herein, the term "degradation" refers to the ability of a polymer in a polymeric material to decompose due to environmental exposure such as pH (e.g., under acidic or, more particularly, alkaline conditions), temperature, water, light, enzymes, and natural environmental conditions over a period of time.

It has been surprisingly found that the polymeric material of the present invention (i.e. a polymeric material comprising a polymer of formula I and/or a polymer of formula II or a polymeric material comprising a polymer of formula III and/or a polymer of formula IV) can be easily degraded. Without wishing to be bound by theory, the structural features of the repeat unit m of the polymeric materials described herein provide the necessary bonds for degradation to allow the polymers of the present invention to readily decompose as shown in example 3.

The use of cyclic ketene diheteropentanone (CKDHO or CKDOO, where X ═ Y ═ oxygen,

figure 1a) as a monomeric precursor for the production of polymers allows for more efficient incorporation of degradable linkages into the polymer, which is not possible when using typical Cyclic Ketene Acetals (CKAs) (see figure 2).

Furthermore, the fraction of degradable bonds in the polymers of the invention is highly tunable over a wide range (e.g. from almost zero to 100%; see tables 1 and 2) with various vinyl comonomers to achieve different properties and degrees of degradability. In addition, the polymers of the present invention can be obtained under mild reaction conditions.

The applications of these degradable polymeric materials disclosed herein are diverse and cover the entire range of applications for which degradable polymers are currently used. Some non-limiting examples of such applications include:

polymeric hydrogels-such as disposable contact lenses, superabsorbent polymers for use in diapers and agriculture, and the like. Hydrogels formed using the polymers disclosed herein will be degradable and thus potentially disposable by flushing down a toilet, where the polymer material will degrade and not cause clogging of the sewage system or long term build-up of polymer waste in the environment (e.g., in the ocean). To obtain hydrogels from the materials disclosed herein, a crosslinking agent may be added to the material used to form the degradable polymeric material. The cross-linking agent may be a bifunctional material that can react with two (or more) growing polymer chains to form a cross-linked structure. Any suitable crosslinking agent may be used, provided that it is compatible with the polymerization conditions used to make the polymeric materials disclosed herein. For example, the crosslinking agent may be a divinyl monomer such as, but not limited to, divinylbenzene, ethylene glycol dimethacrylate, and ethylene glycol diacrylate.

Similarly, the polymeric materials disclosed herein can be used as degradable plastic materials, producing the same benefits.

Degradable polymeric coatings for a variety of uses can be formed using the polymeric materials disclosed herein. For example, the polymeric materials disclosed herein can be formed as a coating on a substrate that is exposed to seawater. In this application, the anti-fouling material can be uniformly dispersed throughout the polymer matrix. Upon contact with seawater, the polymeric materials described herein will begin to degrade and thus will release the anti-fouling material, thereby preventing fouling of the substrate surface for an extended period of time.

A range of high value materials also require stimuli responsive degradable polymers. For example, degradable polymers can form nanocapsules (e.g., micelles and vesicles) for containing useful active compounds, such as drugs, genes, pesticides, cosmetic molecules, for medical, agrochemical and personal care applications. Due to the stimuli-responsive degradable nature of polymers, active compounds can be released in a controlled manner in response to pH, temperature, water, light, enzymes and natural conditions. In particular, the degradation of the polymeric material of the present invention in response to pH is shown in example 3.

Further aspects and embodiments of the invention will now be described by reference to the following non-limiting examples.

Examples

The present invention relates to the use of Cyclic Ketene Diheterocyclopentanones (CKDHOs) (fig. 1a) as monomers to generate polymers that are degradable in the natural environment or in response to external stimuli such as pH, temperature, water, light and enzymes. A schematic of polymer synthesis and degradation is shown in figure 1 b.

When the monomers CKDOO (CKDHO, where X ═ Y ═ oxygen) polymerize, they produce polymers with degradable anhydride ((C ═ O) -O- (C ═ O)) bonds in the polymer backbone (fig. 2 b). Anhydride linkages are generally less stable than ester linkages, are not stable to water, and can be readily metabolized and biodegraded. It is also important that the environmental protection remaining bonds obtained from CKDOO (fig. 2b) are degradable, due to the presence of ester groups on the side chains.

Both the ring opening and the environmentally-friendly leave-on structure obtained from CKDOO are degradable compared to the polymer produced by Cyclic Ketene Acetal (CKA) (fig. 2a), thus indicating that CKDOO monomers are able to produce degradable polymers more efficiently than CKA (fig. 2 b).

In addition, lactic acid or its analogs are produced after degradation of the environmentally-friendly leave-on structure. The resulting lactic acid or its analogs can be reused for the synthesis of CKDOO monomers, providing a possible recycling system. Figures 8 and 9 illustrate possible degradation mechanisms, but as will be appreciated, the invention is not limited to these mechanisms. The degradation of the polymer is further discussed in example 3.

Material

2-acetoxyisobutyryl chloride (> 97%, Tokyo Chemical Industry (TCI)), 2-hydroxyisobutyric acid (> 98%, TCI), acetyl chloride (> 99.0%, Sigma-Aldrich), oxalic acid (> 99.0%, Sigma-Aldrich), triethylamine (> 99.0%, TCI), anhydrous methylene chloride (> 99.0%, TCI), hexane (> 99%, International Scientific, Singapore), diethyl ether (ACS reagent grade, VWR International), ethanol (> 99.5%, anhydrous (Absolute), Fisher Scientific), Tetrahydrofuran (THF) (> 99.5%, Kanto Chemical, Japan), N-Dimethylformamide (DMF) (> 99.5%, Kanto), 2' -azobis (2, 4-dimethylvaleronitrile) (V65) (95%, Wako, Chemical), Ethylenecarbonate (EC, > 99%, diethylene glycol (TCI), diethylene glycol (TCI 99%, dimethyl ether), TCI), toluene (ACS reagent grade, VWR International), 2-iodo-2-methylpropionitrile (CP-I) (> 95%, TCI), tetrabutylammonium iodide (BNI) (> 98%, TCI), methanol (ACS reagent grade, VWR International), tert-butyl peroxybenzoate (≧ 98.0%, Sigma-Aldrich), Methyl Methacrylate (MMA) (> 99.8%, TCI), poly (ethylene glycol) methyl ether methacrylate (PEGMA) (average molecular weight ═ 300) (98%, Sigma-Aldrich, USA), Butyl Acrylate (BA) (> 99%, TCI), Acrylonitrile (AN) (> 99%, TCI), Butyl Methacrylate (BMA) (> 99.8%, TCI), styrene (St) (> 99.8%, TCI), 2- (dimethylamino) ethyl methacrylate (DMAEMA) (> 98.5%, TCI), 2-methoxyethyl acrylate (MEA) (> 98%, TCI) and N, N-Dimethylacrylamide (DMA) (> 99.0%, TCI) were used as received.

Analytical method

THF-GPC analysis was performed on a column equipped with two Shodex KF-804L mixed gels (300 X8.0mm; bead size. about.7 μm;

) Shimadzu i-Series Plus liquid chromatograph LC-2030c Plus (Kyoto, Japan). DMF-GPC analysis was performed on Shimadzu i-Series Plus liquid chromatograph LC-2030c Plus (Kyoto, Japan) equipped with two Shodex KF-804L mixed gel columns. The flow rates were 0.7mL/min (THF) and 0.8mL/min (DMF), and LiBr (10mM) was added to the DMF eluent. For THF-GPC and DMF-GPC, a refractive index detector (RID-20A) was used for sample detection. For both THF-GPC and DMF-GPC systems, the column system was calibrated using the standard poly (methyl methacrylate) (PMMA).

NMR spectra were recorded on a Bruker (Germany) AV500 spectrometer (500MHz), a BBFO400 spectrometer (400MHz) or an AV 300(300MHz) at ambient temperature. CDCl₃And acetonitrile-d₃(Cambridge Isotrope Laboratories, USA) was used as the solvent for NMR analysis and chemical shifts were calibrated using either residual non-deuterated solvent or Tetramethylsilane (TMS) as an internal standard. Monomer conversion and monomer composition in the resulting polymer¹H NMR determination.

General procedure 1 Synthesis of DMDL

5, 5-dimethyl-2-methylene-1, 3-dioxolan-4-one (DMDL) was synthesized according to reported literature (R.Friary, J.heterocyclic. chem.1978,15, 63). A solution of 2- (acetoxy) -2-methylpropanoyl chloride (25.0g, 0.15mol) and triethylamine (18.4g, 0.18mol) was dissolved in dry Dichloromethane (DCM) (100 mL). The mixture was heated under nitrogen at reflux. After 5h, the mixture was cooled and diluted with 100mL of 1:1 ether-hexane. The resulting suspension was filtered and the solvent was evaporated with a rotary evaporator. The residual liquid was fractionated at 40 ℃ at 15 torr to give DMDL (8.64g, 0.07mol) in 44% yield.

¹H NMR(400MHz,298K,CDCl₃)δ3.70(d,J＝4.0Hz,1H,–C＝CH₂),3.62(d,J＝4.0Hz,1H–C＝CH₂),1.55(s,6H,-(CH₃)₂)ppm。

¹³C NMR(400MHz,298K,CDCl₃)δ172.3,157.4,79.3,61.5,23.7ppm。

General method 2 Synthesis of PhDL

2-acetoxy-2-phenylpropionic acid (2) was synthesized according to the reported literature (f.k.thayer, org.synth.1925,4, 1). 2-hydroxy-2-phenylpropionic acid hydrate (1, 10.0g, 60mmol) was suspended in anhydrous DCM (60mL) under Ar, then acetyl chloride (12mL, 2.8 eq, 168mmol) was added dropwise. The mixture was gradually clarified and heated to reflux. After 2h, the resulting solution was cooled and concentrated under vacuum to remove all volatiles. The residue was crystallized to give 2 as a white solid (12.0g, 57.6mol) in 96% yield.

3. Synthesis of 1-chloro-1-oxoylidene-2-phenylpropan-2-yl acetate (3) was synthesized using a modified procedure according to the reported literature (M.Rachwalski, et al., Tetrahedron: Asymmetry,2013,24, 689). 2-acetoxy-2-phenylpropionic acid (2, 12.0g, 57.6mmol) was dissolved in anhydrous DCM (60mL) under Ar, followed by careful addition of dimethylformamide (0.45mL, 10 mol%, 5.8mmol) and oxalyl chloride (5.4mL, 1.1 equiv., 63.4 mmol). The mixture was allowed to stir overnight. After completion of the reaction, the resulting solution was concentrated under vacuum to remove all volatiles. The residue was used directly in the following step as 3(13.0g, 57.4mol, 99% yield) as a yellow viscous semisolid.

Synthesis of PhDL according to the reported literature (r. friary, j. heterocyclic. chem.1978,15,63) 5-methyl-2-methylene-5-phenyl-1, 3-dioxolan-4-one (PhDL) was synthesized using a modified procedure. 1-chloro-1-oxoylidene-2-phenylpropan-2-yl acetate (3, 13.0g, 57.4mmol) is dissolved in dry DCM (100mL) under Ar, and triethylamine (37.6g, 4.7 equiv., 270mmol) is added. The mixture was heated to reflux. After 2h, the mixture was cooled, concentrated and precipitated with 100mL diethyl ether. The resulting suspension was filtered and the solvent was evaporated with a rotary evaporator. The residual liquid was fractionated at 60 ℃ at 0.1 torr to give PhDL (9.8g, 51.5mmol) in 90% yield.

¹H NMR(400MHz,298K,CDCl₃)δ7.54(d,J＝1.5Hz,2H,Ar-H),7.47–7.35(m,3H,Ar-H),3.85–3.79(m,2H,–C＝CH₂),1.90(s,3H,-CH₃)ppm。

¹³C NMR(400MHz,298K,CDCl₃)δ170.5,157.5,137.3,129.1,128.9,124.5,81.8,62.1,25.1ppm。

Example 1 polymerization of DMDL to form Poly (DMDL) (PDMDL) of the invention

The poly (DMDL) of the invention (PDMDL) is synthesized by free radical polymerization using a combination of DMDL monomer (with or without other comonomers), initiator (CP-I), catalyst (tetrabutylammonium iodide, BNI) and free radical initiator (V65, AIBN or tert-butyl peroxybenzoate). The monomers, initiators, catalysts and free radical initiators used in this example are summarized in fig. 3.

Experimental procedures

In a typical run, a mixture of (main) monomer (1 equivalent), DMDL (1 equivalent), CP-I (alkyl iodide initiator), catalyst, free radical initiator and solvent (50 wt%) was heated in a Schlenk flask at 70-110 ℃ under an argon atmosphere under magnetic stirring. After a specified time t, an aliquot of the solution (0.1mL) was taken, quenched to room temperature, and purified by Gel Permeation Chromatography (GPC) and ¹H NMR was conducted. At the end of the reaction, the mixture was diluted and reprecipitated to yield a polymer. The collected polymer was dried under vacuum. The experimental conditions and results are summarized in table 1 below. The NMR chemical shifts (FIGS. 5a and b) of PMMA-r-PDMDL as synthesized (Table 1, entry 3) are shown below.

¹H NMR(400MHz,298K,CDCl₃)δ3.60(s,3H,-CH₂C(CH₃)C＝OCH₃),2.27(br,2H,-CH₂CCO(CH₃)₂),2.01-1.74(br,2H,-CH₂CC＝OCH₃),1.48(s,6H,CH₂CCO(CH₃)₂) 1.01 and 0.84 (CH)₂C(CH₃)C＝OCH₃)ppm。

¹³C NMR(400MHz,298K,CDCl₃)δ178.0,177.7,176.8,176.5,174.7,109.4,77.7,54.4,25.8,25.5,18.7,16.3ppm。

For the homopolymerization of DMDL (table 1, entry 1), a mixture of DMDL (0.1g, 0.78mmol), V65(1.94mg, 7.81 μmol) and toluene (solvent, 50 wt%) was heated in a schlank flask at 70 ℃ under argon atmosphere under magnetic stirring. After 11h, the polymer solution was diluted with tetrahydrofuran and the polymer was reprecipitated twice in hexane for purification. The collected polymer was dried in vacuo and characterized accordingly. The NMR chemical shifts of the as-synthesized PDMDL are listed below (FIGS. 4a and b).

¹H NMR(400MHz,298K,CDCl₃)δ2.74(br,2H,-CH₂C(CO)₂),1.52(s,6H,-(CH₃)₂)ppm。¹³C NMR(400MHz,298K,CDCl₃)δ173.8,106.4,77.3,49.8,23.7ppm。

Results and discussion

Poly (DMDL) (PDMDL) was successfully synthesized by homopolymerization of DMDL (using DMDL only; no comonomer) at 70 ℃ (table 1, entry 1, fig. 4a and b). It was observed that both open loop and eco-retention forms could be produced. The present invention does not appear to limit the polymer structure to the ring-opened or ring-retained form, and the resulting polymer may contain both the ring-opened and ring-retained form in a mixed manner. Of homopolymer PDMDL ¹³The C NMR spectrum shows that the environmentally conserved form exists as the predominant structure in the polymer (C ═ O signal a in fig. 4 b).

The copolymerization of DMDL with other comonomers was performed. For example, DMDL and Methyl Methacrylate (MMA) were mixed together at equal feed molar ratios (table 1, entry 3) and a feed molar ratio of MMA: DMDL of 3:1 (table 1, entry 4), respectively. From the NMR spectra, it was observed that DMDL polymerizes by a ring retention mechanism to form a polymer with mainly environmentally friendly retention structure (fig. 5a and b, table 1, entry 3). Fraction of DMDL in the Polymer (F)_DMDL) Is based on¹The integral ratio of the methylene protons of DMDL (at about 2-2.5 ppm-designated as b in FIG. 5 a) to the methyl protons of MMA (designated as a in FIG. 5 a) in the H NMR spectrum.

In addition, DMDL monomers were observed to be compatible with several methacrylates and acrylates. The polymerization results of poly (ethylene glycol) methyl ether methacrylate (PEGMA), Butyl Methacrylate (BMA), Butyl Acrylate (BA), Acrylonitrile (AN), styrene (St), 2-methoxyethyl acrylate (MEA), 2- (dimethylamino) ethyl methacrylate (DMAEMA), N-Dimethylacrylamide (DMA), vinyl acetate (VAc), benzyl methacrylate (BzMA), Lauryl Methacrylate (LMA), 2-ethylhexyl methacrylate (EHMA), N-vinylpyrrolidone (NVP), and Stearyl Methacrylate (SMA) with DMDL are summarized in Table 1 (entries 5-17, 23-28). In addition, polymerization at higher temperatures was also investigated (Table 1, entries 18-22).

Fraction of DMDL in the resulting polymer (F)_DMDL) Based on information from¹The integral ratio of the H NMR spectrum was calculated, and the value was determined to be 7% to 80%. It is inferred that DMDL is randomly incorporated into the polymer at the respective monomer ratios. When the comonomer free radical is less stable (more reactive), the fraction of DMDL in the resulting polymerThe number increases. Thus, in principle, the fraction of DMDL is based on methacrylate<Styrene (meth) acrylic acid ester<Acrylic esters<The order of acrylonitrile increases. The order may vary depending on the functional groups contained in the monomers.

Example 2 polymerization of PhDL to form Poly (PhDL) (PPhDL) of the invention

The poly (PhDL) (PPhDL) of the invention is synthesized by free radical polymerization using a combination of PPhDL monomer (with or without other comonomers), initiator (CP-I), catalyst (tetrabutylammonium iodide, BNI) and free radical initiator (V65, AIBN or tert-butyl peroxybenzoate). The monomers, initiators, catalysts and free radical initiators used in this example are summarized in fig. 3.

Experimental procedures

The synthetic procedure for PPhDL was similar to that for PDMDL in example 1, except DMDL was replaced with PhDL. Therefore, for the sake of brevity, these procedures will not be discussed herein. The experimental conditions and results are summarized in table 2 below.

Results and discussion

Copolymerization of PhDL and Methyl Methacrylate (MMA) was performed by feeding them at equal feed molar ratios (table 2, entry 1) and a feed molar ratio of 3:1, MMA: PhDL ratio (table 2, entry 2) was mixed. The amounts of CP-I, BNI and free radical initiator were varied accordingly to optimize the efficacy of the polymerization reaction. The fraction of PhDL in the polymer is based on¹The integral ratio of phenyl protons of PhDL (at about 7.2-7.6 ppm-designated as b, c, d in FIG. 6 a) to methyl protons of MMA (designated as a in FIG. 6 a) in the H NMR spectrum. Of PMMA-r-PPhDL of the present invention (Table 2, entry 2)¹³The C NMR spectrum is shown in FIG. 6 b.

In addition, PhDL monomers were observed to react with several methacrylates, acrylates and theirThe monomers are compatible. The polymerization results of poly (ethylene glycol) methyl ether methacrylate (PEGMA), Butyl Acrylate (BA) and Acrylonitrile (AN) with PhDL are summarized in table 2 (entries 3-6). In addition, polymerization at higher temperatures was also investigated (Table 2, entries 7-12). Fraction of PhDL in the resulting polymer (F)_PhDL) Based on information from¹The integral ratio of the H NMR spectrum was calculated, and the value was determined to be 5% to 32%. It was concluded that PhDL was randomly incorporated into the polymer at the respective monomer ratios.

Example 3 degradation of PDMDL, PMMA-r-PDMDL and PPEGMA-r-PDMDL of the invention

To understand the degradability of the polymers of the invention, the as-synthesized polymers (from example 1) were tested under various conditions to investigate the degree of degradation.

Hydrolytic degradation of PDMDL

Mixing PDMDL (M)_n＝109000g/mol，

) (256mg) of the sample was dissolved in dimethyl sulfoxide (DMSO-d)₆) (7mL), and 2mL of NaOH (1M) was added. After heating at 80 ℃ for 17h, by¹H NMR and¹³the solution was analyzed by C NMR. Aliquots of the solutions were analyzed by DMF-GPC (DMF: dimethylformamide).

After addition of NaOH, the GPC result of the mixture showed no peak on the chromatogram (no polymer detected). Complete degradation of PDMDL to 2-hydroxyisobutyric acid (2-HIBA) and other small molecules was observed. In that¹In the H NMR spectrum, the methylene protons of PDMDL at 2-2.5ppm disappeared and a new peak (designated as a in FIG. 7 a) appeared at 1.14 ppm. Furthermore, in¹³In the C NMR spectrum, the peaks at 164ppm (ester carbon) and 106ppm (acetal carbon) of PDMDL disappeared (FIG. 7 b). In particular, the disappearance of the acetal carbon peak at 106ppm indicates a degradation of the polymer backbone.

The general degradation mechanism of the environmentally friendly leave-on structure obtained from CKDOO is depicted in fig. 8a and b. A more detailed mechanism of the PDMDL backbone degradation under alkaline conditions is shown in figure 9. As the mechanism shows, 2-HIBA (or other equivalent) is generated upon degradation, which is the starting material for the synthesis of DMDL (or equivalent). Thus, this indicates the possibility of recycling the degradation by-products for further use, possibly for the regeneration of CKDOO monomer (fig. 8a and b).

As will be appreciated, the mechanisms depicted in fig. 8 and 9 represent some of the possibilities of the proposed mechanism, and the present invention is not limited to these degradation mechanisms. That is, it is likely that other degradation byproducts (other than 2-HIBA) will also be produced.

Degradation of PDMDL using amines

Mixing PDMDL (M)_n＝15800g/mol，

) (100mg) of the sample was dissolved in chloroform (CDCl)₃) (0.4mL), and 0.1mL of phenethylamine was added. The reaction mixture was heated at 50 ℃. After 12h, by¹H NMR and¹³the solution was analyzed by C NMR. Aliquots of the solutions were analyzed by DMF-GPC (DMF: dimethylformamide).

After 12h of reaction, the GPC results of the mixture showed no peaks on the chromatogram (no polymer detected), indicating complete degradation of PDMDL to small molecules. The mechanism of degradation may be similar to that described in FIG. 9, except that the amine acts as a base or nucleophile instead of OH^–And (4) acting. As will be appreciated, the degradation process may also involve other mechanisms.

Hydrolytic degradation of PMMA-r-PDMDL (-r-stands for random copolymer)

PMMA-r-PDMDL (M) with 21% DMDL fraction_n＝17900g/mol，

(20mg) of the sample was dissolved in Tetrahydrofuran (THF) (1mL), and 0.1mL of formazan was addedKOH in alcohol (5% w/v). After a defined time t (e.g. 5min to 24h) at room temperature, the solution is neutralized with 1M HCl and evaporated under vacuum. The residue was dissolved in chloroform (2mL) and filtered. The solution is evaporated under vacuum to give a residue by ¹It was analyzed by H NMR and DMF-GPC (DMF: dimethylformamide).

GPC analysis showed that in 5% (w/v) KOH in methanol, the molecular weight of the polymer (M initially at time zero)_n17900) reduces: 17% after 5 min; 49% after 1 h; and 56% after 24 h. With increasing degradation times of 5min, 1h and 24h, the GPC chromatogram shifted from higher molecular weight (shorter elution time) to lower molecular weight (longer elution time) (fig. 10). The final molecular weight of the polymer was determined to be 7900 g/mol.

PPEGMA-rHydrolytic degradation of PDMDL

PPEGMA-r-PDMDL (M) with 10% DMDL fraction_n＝16500g/mol，

) (30mg) of the sample was dissolved in 3mL of a 5% (w/v) KOH aqueous solution. After 24h at room temperature, the solution was neutralized with 1M HCl and evaporated under vacuum. The residue was dissolved in chloroform (2mL) and filtered. The solution is evaporated under vacuum to give a residue by¹It was analyzed by H NMR and DMF-GPC. PPEGMA homopolymer (M) without DMDL was also tested using the same procedure_n＝22000g/mol，

) Degradation of (2).

GPC analysis showed that after 24h in 5% (w/v) aqueous KOH, the molecular weight of the polymer (the initial M at time zero)_n16500) by 60%. The GPC chromatogram shifted from a higher molecular weight (shorter elution time) to a lower molecular weight (longer elution time) (fig. 11 a). The final molecular weight of the polymer was 6500 g/mol. PPEGMA homopolymer without DMDL The GPC chromatogram of (a) did not shift significantly (fig. 11b), indicating little or no degradation of the homopolymer. The results clearly show that the incorporation of DMDL in the polymer gives degradability characteristics.

Claims

1. A degradable polymeric material comprising a polymer of formula I:

wherein:

m has a non-zero integer value;

n has a value of 0 or a non-zero integer value;

X₁and X₂Independently selected from O, NR_aOr S;

R_ais H or C₁To C₆An alkyl group;

when present, R₃Is H or C₁To C₆An alkyl group;

when present, Y is selected from:

CN；

C₁to C₂₀An alkyl group which is unsubstituted or substituted by one or more of: halogen, aromatic or heteroaromatic ring systems (said aromatic or heteroaromatic ring systems being unsubstituted or selected from halogen, C₁To C₆Alkyl, OR_5aAnd NR_5bR_5cSubstituted with one or more groups of (a)), epoxy groups, cycloalkyl ring systems (said Cycloalkyl ring systems unsubstituted or substituted by one or more members selected from halogen, C₁To C₆Alkyl, OR_5dAnd NR_5eR_5fSubstituted with one OR more groups of (a), OR_5g、Si(OR_5h)₃、NR_5iR_5jAnd N⁺R_5kR_5lR_5m；

OR_6a；

-C(＝O)OR_6b；

-A-(OLO)_p-R₇；

each R_5hIndependently represent C₁To C₆An alkyl group;

R_6aand R_6bEach independently represents:

H；

a represents a bond or is-C (═ O) -;

l represents an alkyl chain of 2 to 10 carbon atoms;

p has a value of 1 to 1000;

and salts or solvates thereof.

2. The degradable polymeric material of claim 1 wherein the polymeric material further comprises a polymer of formula II:

wherein, X₁、X₂、m、n、R₁To R₃And the value of Y is defined in claim 1.

3. The degradable polymeric material of claim 1 or claim 2 wherein X is₁And X₂Is O, and X₁And X₂Is independently selected from the otherFrom O, NR_aOr S.

4. The degradable polymeric material of any one of the preceding claims wherein X is₁And X₂Both are O.

5. The degradable polymeric material of any one of the preceding claims wherein R₁And R₂Independently selected from alkyl groups and aromatic groups.

6. The degradable polymeric material of claim 5 wherein R₁And R₂Independently selected from C ₁To C₃An alkyl group and a phenyl group, optionally wherein R₁And R₂Both being methyl radicals or R₁Is a methyl group and R₂Is a phenyl group.

7. The degradable polymeric material of any one of the preceding claims wherein n has a non-zero integer value, optionally wherein the polymer is a random copolymer, a block copolymer or has a portion corresponding to a random copolymer and a portion corresponding to a block copolymer (e.g., the polymer is a random copolymer or a block copolymer, such as a random copolymer).

8. The degradable polymeric material of any one of the previous claims wherein when present, the repeating unit of formula Ia in formula I or formula II:

9. The degradable polymeric material of claim 8 wherein when present, the repeating unit of formula Ia in formula I or formula II:

formed from monomers selected from one or more of the group consisting of: acrylonitrile, styrene, methoxystyrene, butoxystyrene, chloromethylstyrene, chlorostyrene, methyl acrylate, ethyl acrylate, propyl acrylate, n-butyl acrylate, t-butyl acrylate, hexyl acrylate, 2-ethylhexyl acrylate, n-octyl acrylate, nonyl acrylate, decyl acrylate, benzyl acrylate, tetrahydrofurfuryl acrylate, glycidyl acrylate, cyclohexyl acrylate, 2-methoxyethyl acrylate and butoxyethyl acrylate, tris (trialkylsiloxy) derivative-acrylic acid ester and fluoroalkyl acrylate, methyl methacrylate, ethyl methacrylate, propyl methacrylate, n-butyl methacrylate, t-butyl methacrylate, hexyl methacrylate, 2-ethylhexyl methacrylate, n-octyl methacrylate, n-butyl acrylate, or a, Nonyl methacrylate, decyl methacrylate, benzyl methacrylate, tetrahydrofurfuryl methacrylate, glycidyl methacrylate, cyclohexyl methacrylate, 2-methoxyethyl methacrylate, butoxyethyl methacrylate, tris (trialkylsiloxy) derivative-methacrylate, fluoroalkyl methacrylate, hydroxystyrene, styrenesulfonic acid, sodium styrenesulfonate, styreneboric acid, acrylamide, N-isopropylacrylamide, N-dimethylacrylamide, N-methylolacrylamide, N-hydroxyethylacrylamide, methacrylamide, N-isopropylacrylamide, N-dimethylmethacrylamide, N-methylolmethacrylamide, N-hydroxyethylmethacrylamide, N-methylolmethacrylamide, N-methylol methacrylamide, N-methylol acrylamide, N-alkyl methacrylate, N-hydroxy-methyl methacrylate, N-ethyl methacrylate, N-methyl methacrylate, N-N-methyl acrylate, N-N-methyl methacrylate, N-N-butyl acrylate, acrylic acid, hydroxyalkyl acrylates (e.g. 2-hydroxyethyl acrylate), 2-hydroxypropyl acrylate, glycerol monoacrylate, diethylene glycol acrylate, polyethylene glycol acrylate, methoxy tetraethylene glycol acrylate, methoxy polyethylene glycol acrylate, 2- (dimethylamino) ethyl acrylate, 3-chloro-2-hydroxypropiopropylacrylate Esters, 2-hydroxy-3-phenoxypropyl acrylate, 2-acryloyloxyethylphosphorylcholine, 2- (N, N-diethyl-N-methylamino) ethyl acrylate +/trifluoromethanesulfonylimide, 2- (N-ethyl-N-methyl-N-hydroamino) ethyl acrylate +/trifluoromethanesulfonylimide (N (CF)₃SO₂)^2-) Salt, 1-ethyl-3-methylimidazolium acrylate +/fluorohydrogenate ((FH) nF)^-) Salts, methacrylic acid, 2-hydroxyethyl methacrylate, 2-hydroxypropyl methacrylate, glycerol monomethacrylate, diethylene glycol methacrylate and polyethylene glycol methacrylate, methoxy tetraethylene glycol methacrylate, methoxy polyethylene glycol methacrylate, 2- (dimethylamino) ethyl methacrylate, 3-chloro-2-hydroxypropyl methacrylate, 2-hydroxy-3-phenoxypropyl methacrylate, 2-acryloxyethylphosphorylcholine, 2- (N, N-diethyl-N-methylamino) ethyl ester +/trifluorosulfonyliminium salt, 2- (N-ethyl-N-methyl-N-hydroamino) ethyl methacrylate +/trifluorosulfonyliminium (N (CF).₃SO₂)^2-) Salt and 1-ethyl-3-methylimidazolium methacrylate +/fluorohydrogenate ((FH) nF)^-) And (3) salt.

10. The degradable polymeric material of claim 8 or claim 9 wherein the repeating unit of formula Ia in formula I or formula II, when present:

11. The degradable polymeric material of any one of the preceding claims wherein there is presentAt the time of R₃Is H or C₁To C₃Alkyl, optionally wherein R₃Is H or methyl.

12. The degradable polymeric material of any one of the preceding claims wherein when present, Y is selected from the group consisting of:

CN；

C₁to C₁₀An alkyl group which is unsubstituted or substituted by one or more of: halogen, benzene ring (the benzene ring is unsubstituted or selected from halogen, C₁To C₃Alkyl, OR_5aAnd NR_5bR_5cSubstituted with one or more groups of (a)), an epoxy group, a cycloalkyl ring system (said cycloalkyl ring system being unsubstituted or selected from halogen, C₁To C₃Alkyl, OR_5dAnd NR_5eR_5fSubstituted with one OR more groups of (a), OR _5g、Si(OR_5h)₃、NR_5iR_5jAnd N⁺R_5kR_5lR_5m；

OR_6a；

-C(＝O)OR_6b；

-A-(OLO)_p-R₇；

each R_5hIndependently represent C₁To C₆An alkyl group;

R_6aand R_6bEach independently represents:

H；

C₁to C₁₀An alkyl group which is unsubstituted or substituted by one or more of: halogen, aromatic or heteroaromatic ring systems (the aromatic or heteroaromatic ring systems being unsubstituted or selected from halogenElement, C₁To C₆Alkyl, OR_8aAnd NR_8bR_8cSubstituted with one or more groups of (a)), an epoxy group, a cycloalkyl ring system (said cycloalkyl ring system being unsubstituted or selected from halogen, C₁To C₆Alkyl, OR_8dAnd NR_8eR_8fSubstituted with one OR more groups of (a), OR_8g、Si(OR_8h)₃、NR_8iR_8jAnd N⁺R_8kR_8lR_8m；

a represents a bond or is-C (═ O) -;

l represents an alkyl chain of 2 to 4 carbon atoms;

p has a value of 5 to 500;

R₇is represented by C₁To C₁₀An alkyl group which is unsubstituted or substituted by one or more of: halogen, aromatic or heteroaromatic ring systems (said aromatic or heteroaromatic ring systems being unsubstituted or selected from halogen, C₁To C₆Alkyl, OR_10aAnd NR_10bR_10cSubstituted with one or more groups of (a)), an epoxy group, a cycloalkyl ring system (said cycloalkyl ring system being unsubstituted or selected from halogen, C ₁To C₆Alkyl, OR_10dAnd NR_10eR_8fSubstituted with one OR more groups of (a), OR_10g、Si(OR_10h)₃、NR_10iR_10jAnd N⁺R_10kR_10lR_10m；

R_8hand R_10hEach independently represents C₁To C₃An alkyl group.

13. The degradable polymeric material of claim 12 wherein when present, Y is selected from the group consisting of:

CN；

OR_6a；

-C(＝O)OR_6b；

-A-(OLO)_p-R₇；

each R_5hIndependently represent C₁To C₆An alkyl group;

R_6aand R_6bEach independently represents:

H；

C₁to C₆An alkyl group which is unsubstituted or substituted by one or more of: halogen, aromatic or heteroaromatic ring systems (said aromatic or heteroaromatic ring systems being unsubstituted or selected from halogen, C ₁To C₆Alkyl, OR_8aAnd NR_8bR_8cSubstituted with one or more groups)Epoxy groups, cycloalkyl ring systems (said cycloalkyl ring systems being unsubstituted or selected from halogen, C₁To C₆Alkyl, OR_8dAnd NR_8eR_8fSubstituted with one OR more groups of (a), OR_8g、Si(OR_8h)₃、NR_8iR_8jAnd N⁺R_8kR_8lR_8m；

a represents a bond or is-C (═ O) -;

l represents an alkyl chain of 2 to 4 carbon atoms;

p has a value of 10 to 250;

R_8hand R_10hEach independently represents C₁To C₃An alkyl group.

14. Degradable according to any of the preceding claimsA depolymerized polymeric material, wherein, when n has a non-zero integer value, the [ alpha ], [ alpha ] or ]_mThe repeating units in the degradable polymer material are 0.01 to 99.99mol percent.

15. The degradable polymeric material of claim 14 wherein when n has a nonzero integer value, [ solution ], or [ solution ], or [ solution ], [ solution ] of a non-zero integer value]_mThe repeating units within constitute 0.05 to 50 mol%, such as 0.1 to 30 mol%, such as 0.5 to 10 mol%, such as 1 to 5 mol% of the degradable polymeric material.

16. The degradable polymeric material of any one of the preceding claims wherein the degradable polymeric material has a number average molecular weight (M)_n) Is from 150 to 10,000,000 daltons, such as from 500 to 5,000,000 daltons, such as from 1,000 to 1,000,000 daltons.

17. The degradable polymeric material of any one of the preceding claims wherein the degradable polymeric material has a number average molecular weight (M)_n) From 500 to 200,000 daltons, such as from 2,000 to 100,000 daltons.

18. A degradable polymeric material comprising a polymer of formula III:

wherein:

m has a non-zero integer value;

n has a value of 0 or a non-zero integer value;

X₁and X₂Independently selected from O, NR_aOr S;

R_ais H or C₁To C₆An alkyl group;

when present, R₃Is H or C₁To C₆An alkyl group;

when present, Y is selected from:

CN；

OR_6a；

-C(＝O)OR_6b；

-A-(OLO)_p-R₇；

each R_5hIndependently represent C₁To C₆An alkyl group;

R_6aand R_6bEach independently represents:

H；

C₁to C₂₀An alkyl group which is unsubstituted or substituted by one or more of: halogen, aromatic or heteroaromatic ring systems (said aromatic or heteroaromatic ring systems being unsubstituted or selected from halogen, C ₁To C₆Alkyl, OR_8aAnd NR_8bR_8cSubstituted with one or more groups of (a)), an epoxy group, a cycloalkyl ring system (said cycloalkyl ring system being unsubstituted or selected from halogen, C₁To C₆Alkyl, OR_8dAnd NR_8eR_8fSubstituted with one OR more groups of (a), OR_8g、Si(OR_8h)₃、NR_8iR_8jAnd N⁺R_8kR_8lR_8m；

a represents a bond or is-C (═ O) -;

l represents an alkyl chain of 2 to 10 carbon atoms;

p has a value of 1 to 1000;

and salts or solvates thereof.

19. The degradable polymeric material of claim 18 wherein the polymeric material further comprises a polymer of formula IV:

Wherein, X₁、X₂、m、n、R₃、R₁₁To R₁₆And the value of Y is as defined in claim 18.

20. The degradable polymeric material of claim 18 or claim 19 wherein X₁And X₂Is O, and X₁And X₂Is independently selected from O, NR_aOr S.

21. The degradable polymeric material of any one of claims 18 to 20 wherein X₁And X₂Both are O.

22. The degradable polymeric material of any one of claims 18 to 21 wherein R₁₁To R₁₆Independently selected from H, alkyl groups and aromatic groups, or R₁₃To R₁₆Together with the carbon atoms to which they are attached form an unsubstituted phenyl ring.

23. According to claim 22The degradable polymer material, wherein R₁₁To R₁₆Independently selected from H, C₁To C₃Alkyl radicals and phenyl radicals, or R₁₃To R₁₆Together with the carbon atoms to which they are attached form an unsubstituted benzene ring.

24. The degradable polymeric material of any one of claims 18 to 23 wherein n has a non-zero integer value, optionally wherein the polymer is a random copolymer, a block copolymer or has a portion corresponding to a random copolymer and a portion corresponding to a block copolymer (e.g. the polymer is a random copolymer or a block copolymer such as a random copolymer).

25. The degradable polymeric material of any one of claims 18 to 24 wherein when present, the repeat unit of formula Ia in formula III or formula IV:

26. The degradable polymeric material of claim 25 wherein when present, the repeating unit of formula Ia in formula III or formula IV:

formed from monomers selected from one or more of the group consisting of: acrylonitrile, styrene, methoxystyrene, butoxystyrene, chloromethylstyrene, chlorostyrene, methyl acrylate, ethyl acrylate, propyl acrylate, n-butyl acrylate, tert-butyl acrylate, hexyl acrylate, 2-ethylhexyl acrylateN-octyl acrylate, nonyl acrylate, decyl acrylate, benzyl acrylate, tetrahydrofurfuryl acrylate, glycidyl acrylate, cyclohexyl acrylate, 2-methoxyethyl acrylate and butoxyethyl acrylate, tris (trialkylsiloxy) derivative-acrylates and fluoroalkyl acrylates, methyl methacrylate, ethyl methacrylate, propyl methacrylate, n-butyl methacrylate, t-butyl methacrylate, hexyl methacrylate, 2-ethylhexyl methacrylate, n-octyl methacrylate, nonyl methacrylate, decyl methacrylate, benzyl methacrylate, tetrahydrofurfuryl methacrylate, glycidyl methacrylate, cyclohexyl methacrylate, 2-methoxyethyl methacrylate, butoxyethyl methacrylate, tris (trialkylsiloxy) derivative-methacrylates, Fluoroalkyl methacrylate, hydroxystyrene, styrenesulfonic acid, sodium styrenesulfonate, styreneboric acid, acrylamide, N-isopropylacrylamide, N-dimethylacrylamide, N-methylolacrylamide, N-hydroxyethylacrylamide, methacrylamide, N-isopropyl methacrylamide, N-dimethylmethacrylamide, N-methylolmethacrylamide, N-hydroxyethylmethacrylamide, acrylic acid, hydroxyalkyl acrylates (e.g., 2-hydroxyethyl acrylate), 2-hydroxypropyl acrylate, glycerol monoacrylate, diethylene glycol acrylate, polyethylene glycol acrylate, methoxy tetraethylene glycol acrylate, methoxy polyethylene glycol acrylate, 2- (dimethylamino) ethyl acrylate, methyl ethyl acrylate, and the like, 3-chloro-2-hydroxypropyl acrylate, 2-hydroxy-3-phenoxypropyl acrylate, 2-acryloyloxyethylphosphorylcholine, 2- (N, N-diethyl-N-methylamino) ethyl acrylate +/trifluoromethanesulfonimide onium acrylate, 2- (N-ethyl-N-methyl-N-hydroamino) ethyl acrylate +/trifluoromethanesulfonimide onium (N (CF) ₃SO₂)^2-) Salt, 1-ethyl-3-methylimidazolium acrylate +/fluorohydrogenate ((FH) nF^-) Salts, methacrylic acid, 2-hydroxyethyl methacrylate, 2-hydroxypropyl methacrylate, glycerol monomethacrylate, diethylene glycol methacrylate and polyethylene glycol methacrylate, methoxy tetraethylene glycol methacrylate, methoxy polyethylene glycolAlcohol methacrylate, 2- (dimethylamino) ethyl methacrylate, 3-chloro-2-hydroxypropyl methacrylate, 2-hydroxy-3-phenoxypropyl methacrylate, 2-acryloxyethyl phosphorylcholine, 2- (N, N-diethyl-N-methylamino) ethyl methacrylate +/trifluoromethanesulfonylimide, 2- (N-ethyl-N-methyl-N-hydro-amino) ethyl methacrylate +/trifluoromethanesulfonylimide (N (CF)₃SO₂)^2-) Salt and 1-ethyl-3-methylimidazolium methacrylate +/fluorohydrogenate ((FH) nF^-) And (3) salt.

27. The degradable polymeric material of claim 25 or claim 26 wherein when present, the repeat unit of formula Ia in formula III or formula IV:

28. The degradable polymeric material of any one of claims 18 to 27 wherein R, when present₃Is H or C₁To C₃Alkyl, optionally wherein R₃Is H or methyl.

29. The degradable polymeric material of any one of claims 18 to 28 wherein when present, Y is selected from:

CN；

OR_6a；

-C(＝O)OR_6b；

-A-(OLO)_p-R₇；

each R_5hIndependently represent C₁To C₆An alkyl group;

R_6aand R_6bEach independently represents:

H；

Cycloalkyl ring systems (said cycloalkyl ring systems being unsubstituted or selected from haloElement, C₁To C₆Alkyl, OR_9aAnd NR_9bR_9cSubstituted with one or more groups of (a);

a represents a bond or is-C (═ O) -;

l represents an alkyl chain of 2 to 4 carbon atoms;

p has a value of 5 to 500;

R_8hand R_10hEach independently represents C₁To C₃An alkyl group.

30. The degradable polymeric material of claim 29 wherein when present, Y is selected from the group consisting of:

A phenyl ring, unsubstituted or selected from halogen, C₁To C₃Alkyl, OR_4a、SO₃H and B (OH)₂Substituted with one or more groups of (a);

CN；

OR_6a；

-C(＝O)OR_6b；

-A-(OLO)_p-R₇；

each R_5hIndependently represent C₁To C₆An alkyl group;

R_6aand R_6bEach independently represents:

H；

a represents a bond or is-C (═ O) -;

l represents an alkyl chain of 2 to 4 carbon atoms;

p has a value of 10 to 250;

R_8hand R_10hEach independently represents C₁To C₃An alkyl group.

31. The degradable polymeric material of any one of claims 18 to 30 wherein when n has a non-zero integer value, and]_mthe repeating units in the degradable polymer material account for 0.01 to 99.99 wt%.

32. The degradable polymeric material of claim 31 wherein when n has a non-zero integer value]_mThe repeating units in (b) constitute 0.05 to 50 wt%, such as 0.1 to 30 wt%, such as 0.5 to 10 wt%, such as 1 to 5 wt% of the degradable polymeric material.

33. According to the rightThe degradable polymeric material of any one of claims 18 to 32 wherein the degradable polymeric material has a number average molecular weight (M)_n) Is from 180 to 10,000,000 daltons, such as from 500 to 5,000,000 daltons, such as from 1,000 to 1,000,000 daltons.

34. The degradable polymeric material of any one of claims 18 to 33 wherein the degradable polymeric material has a number average molecular weight (M)_n) From 500 to 200,000 daltons, such as from 2,000 to 100,000 daltons.

35. A method of forming the degradable polymeric material of any one of claims 1 to 17, the method comprising the steps of, mixing:

a repeat unit corresponding to formula I or formula II as defined in any one of claims 1 to 17]_mA first monomer precursor of (a); and

when n has a non-zero integer value, corresponds to the repeating unit of formula I or formula II as defined in any one of claims 1 to 17]_nA second monomer precursor of (2), with

One or more of an initiator compound, a free radical initiator, a catalyst and a solvent, and allowing the polymerization reaction to proceed for a period of time to provide the degradable polymeric material of any one of claims 1 to 17.

36. A method of forming the degradable polymeric material of any one of claims 18 to 34, said method comprising the steps of, mixing:

a repeat unit corresponding to formula III or formula IV as defined in any one of claims 18 to 34]_mA first monomer precursor of (a); and

when n has a non-zero integer value, corresponds to the repeating unit of formula III or formula IV as defined in any one of claims 18 to 34]_nA second monomer precursor of (2), with

One or more of an initiator compound, a free radical initiator, a catalyst and a solvent, and allowing the polymerization reaction to proceed for a period of time to provide the degradable polymeric material of any one of claims 18 to 34.