US 2020/0262802 A1Published application

Photo-crosslinked hydrogel material and preparation, composition, and application thereof photo-crosslinked hydrogel

AssigneeZhongshan Guanghe Medical Technology Co., Ltd

InventorsLinyong Zhu, Yujie Hua, Qiuning Lin, Yiqing Zhang, Chunyan BAO, Xuepeng Zhong

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Abstract

This invention provides preparations, compositions, products, and applications of photo-crosslinked hydrogels. Component A—a photosensitive polymer derivative, component B—the photoinitiator, and auxiliary component C—other biocompatible polymer derivative each are respectively dissolved in a biocompatible medium to obtain solution A, solution B, and solution C. The solution A, the solution B, and the optional solution C are mixed homogenously to obtain a hydrogel precursor solution. The hydrogel precursor solution is subject to irradiation of the UV light for photocoupled crosslinking to form a photo-crosslinked hydrogel. The photo-crosslinked hydrogel exhibit rapid speed of photo-curing, strong tissue adhesion, excellent mechanical properties, good biocompatibility, and excellent clinical operability. In addition, this invention also provides a kit for making the photo-crosslinked hydrogel, and applications thereof in tissue engineering, regenerative medicine, 3D printing, and as a carrier of cell, protein, or drug.

Claims26

Dependent claims

A cyclic o-nitrobenzyl phototrigger as shown in Formula I-2,

where,
X is O, S or N, when X═O, the cyclic o-nitrobenzyl phototrigger is a cyclic o-nitrobenzyl alcohol phototrigger;
when X═S, the cyclic o-nitrobenzyl phototrigger is a cyclic o-nitrobenzyl sulfide phototrigger;
when X═N, the cyclic o-nitrobenzyl phototrigger is a cyclic o-nitrobenzyl amine phototrigger;
R1 is connected with X and one of R2, R3, R4, and R5 to form a cyclic structure,
R′ is selected from the group consisting of a hydrogen atom, a halogen atom, a hydroxyl group, a sulphydryl group, an amine group, a nitro group, a cyano group, an aldehyde group, a ketone group, an ester group, an amide group, a phosphonic acid group, a phosphonate group, a sulfonate group, a sulfonic acid ester group, a sulfonyl group, a sulfoxide group, an aryl group, a heteroaryl group, an alkyl group, an alkylene group, a modified alkyl group, and a modified alkylene group,
R1 is selected from the group consisting of a hydrogen atom, an ether group, an ester group, a carbonate group, an amino formate ester group, a mercaptoformic ester group, and phosphoric acid ester group,
R2, R3, R4, R5 are each independently selected from the group consisting of a hydrogen atom, a halogen atom, a hydroxyl group, a mercapto group, an amine group, a nitro group, a cyano group, an aldehyde group, a ketone group, a carboxyl group, an ester group, an amide group, a phosphonic acid group, a phosphonate group, a sulfonic acid group, a sulfonate group, a sulfone group, a sulfoxide group, an aryl group, a heteroaryl group, an alkyl group, an alkylene group, a modified alkyl group, and a modified alkylene group,
at least two of R2, R3, R4, and R5 are optionally connected via carbon atom(s) to form a saturated or unsaturated alicyclic or heteroalicyclic ring, or an aromatic ring or aromatic heterocyclic ring.

6 more elements

A photosensitive polymer derivative having an o-nitrobenzyl phototrigger represented by Formula I:

The photosensitive polymer derivative having the structure represented by Formula A-I:
wherein the o-nitrobenzyl phototrigger as shown in the Formula I is selected from the structures as shown in Formula I-1 and Formula I-2,
where, in the Formula I-1 and the Formula I-2, X═O, S, or N;
in the Formula I-1 and Formula I-2, R′ is selected from the group consisting of hydrogen atom, halogen atom, hydroxyl group, mercapto group, amine group, nitro group, cyano group, aldehyde group, ketone group, ester group, amide, phosphonic acid, phosphonate, sulfoacid, sulfonate, sulfone, sulfoxide, aryl, heteroaryl, alkyl, alkylene, modified alkyl, and modified alkylene;
in the Formula I-1 and Formula I-2, R1 is selected from the group consisting of a hydrogen atom, an ether group, an ester group, a carbonate group, a urethane group, a mercapto formate group, and a phosphate group;
in the Formula I-1 and Formula I-2, R2, R3, R4, R5 are each independently selected from the group consisting of a hydrogen atom, a halogen atom, a hydroxyl group, a mercapto group, an amine group, a nitro group, a cyano group, an aldehyde group, a ketone group, a carboxyl group, an ester group, amide, a phosphonic acid group, phosphonate, sulfoacid, sulfonate, sulfone, sulfoxide, aryl, heteroaryl, alkyl, alkylene, modified alkyl, and modified alkylene;
in the Formula I-2, R1 is connected to X and one of R2, R3, R4, and R5 to form a cyclic structure;
in the Formula A-I, n≥2;
in the Formula A-I, P1 is a hydrophilic or water-soluble natural polymer or synthetic polymer;
in Formula I-1 and Formula I-2, at least two of R2, R3, R4 and R5 are connected through a carbon atom to form a saturated or unsaturated alicyclic ring, alicyclic heterocycle, aromatic ring, or aromatic heterocycle.

7 more elements

A photosensitive polymer derivative having o-nitrobenzyl phototriggers and double bond groups, the o-nitrobenzyl phototrigger being represented by Formula I:

the photosensitive polymer derivative being represented by Formula A-III:
wherein the o-nitrobenzyl phototrigger as shown in Formula I is selected from the two structures of Formula I-1 and Formula I-2, and the Formula I-2 represents a cyclic o-nitrobenzyl phototriggers,
in Formula I-1 and Formula I-2, X═O, S, or N;
in the Formula I-1 and Formula I-2, R′ is selected from the group consisting of a hydrogen atom, a halogen atom, a hydroxyl group, a sulphydryl group, an amine group, a nitro group, a cyano group, an aldehyde group, a ketone group, an ester group, amide, phosphonic acid, phosphonate, sulfonic, sulfonate, sulfone, sulfoxide, aryl, heteroaryl, alkyl, alkylene, modified alkyl, and modified alkylene;
in Formula I-1 and Formula I-2, R1 is selected from the group consisting of a hydrogen atom, an ether group, an ester group, a carbonate group, a urethane group, a mercapto formate group, and a phosphate group;
in the Formula I-1 and the Formula I-2, R2, R3, R4, R5 are each independently selected from the group consisting of a hydrogen atom, a halogen atom, a hydroxyl group, a sulphydryl group, an amine group, a nitro group, a cyano group, an aldehyde group, a ketone group, an ester group, amide, phosphonic acid, phosphonate, sulfonic, sulfonate, sulfone, sulfoxide, aryl, heteroaryl, alkyl, alkylene, modified alkyl or modified alkylene;
in the Formula I-2, R1 is connected to X and one of R2, R3, R4, and R5 to form a cyclic structure;
in the Formula A-III, R1′, R2′, R3′ are each independently selected from hydrogen, alkyl, modified alkyl, and aryl, R4′ is selected from alkyl, ether group, ester group, and amide group;
in the Formula A-III, at least two of R1′, R2′, R3′ are optionally connected through a carbon atom to form a saturated or unsaturated alicyclic or heteroalicyclic ring;
in the Formula A-III, n≥2;
in the Formula A-III, P1 is a hydrophilic or water-soluble natural polymer or synthetic polymer;
in the Formula I-1 and Formula I-2, at least two of R2, R3, R4, and R5 are connected through a carbon atom to form a saturated or unsaturated alicyclic or heteroalicyclic ring, or to form an aromatic ring or aromatic heterocyclic ring.

9 more elements

A method of making a photo-crosslinked hydrogel material comprising:

dissolving a component A including a photosensitive polymer derivative in a biocompatible medium to obtain a photosensitive polymer solution A;
dissolving a component B including a photoinitiator in a biocompatible medium to obtain a photoinitiator solution B;
obtaining a hydrogel precursor solution by homogeneously mixing solutions including the photosensitive polymer solution A and the photoinitiator solution B;
and
under an irradiation of light, performing free radical cross-linking reaction to form a hydrogel,
wherein the photosensitive polymer derivative is selected from one or more of the followings:
1. a photosensitive polymer derivative containing an o-nitrobenzyl phototriggers as shown in Formula A-I;
and
2. a photosensitive polymer derivative containing both an o-nitrobenzyl phototrigger and double bond functional group as shown in Formula A-III,
wherein the Formula A-1 contains an o-nitrobenzyl phototrigger represented by the Formula I-1 selected from the group consisting of Formula I-1 and Formula I-2, the Formula I-2 represents a cyclic o-nitrobenzyl phototrigger,
where, in the Formula I-1 and the Formula I-2, when X═O, the o-nitrobenzyl phototrigger is an o-nitrobenzyl alcohol phototrigger;
when X═S, the o-nitrobenzyl phototrigger is an o-nitrobenzyl sulphydryl phototriggers;
and when X═N, the o-nitrobenzyl phototrigger is an o-nitrobenzyl amine phototrigger;
in the Formula A-I, Formula A-III, Formula I, Formula I-1, and Formula I-2, R′ is selected from the group consisting of hydrogen atom, halogen atom, hydroxyl group, mercapto group, amine group, nitro group, cyano group, aldehyde group, ketone group, ester group, amide, phosphonic acid, phosphonate, sulfoacid, sulfonate, sulfone, sulfoxide, aryl, heteroaryl, alkyl, alkylene, modified alkyl, and modified alkylene;
in the Formula I-1 and Formula I-2, R1 is selected from the group consisting of a hydrogen atom, an ether group, an ester group, a carbonate group, a urethane group, a mercapto formate group, and a phosphate group;
in the Formula I-1 and Formula I-2, R2, R3, R4, R5 are each independently selected from the group consisting of a hydrogen atom, a halogen atom, a hydroxyl group, a mercapto group, an amine group, a nitro group, a cyano group, an aldehyde group, a ketone group, a carboxyl group, an ester group, amide, a phosphonic acid group, phosphonate, sulfoacid, sulfonate, sulfone, sulfoxide, aryl, heteroaryl, alkyl, alkylene, modified alkyl, and modified alkylene;
in the Formula I-2, X is O, S or NH, R1 is connected to X and one of R2, R3, R4 and R5 to form a cyclic structure;
in the Formula A-III, R1′, R2′, R3′ are selected from the group consisting of a hydrogen atom, an alkyl group, a modified alkyl or aryl group;
R4′ is selected from the group consisting of an alkyl group, an ether group, an ester group, and an amide group;
optionally, in Formula A-III, R1′, R2′ and R3′ are connected with a carbon atom to form a saturated or unsaturated alicyclic ring or alicyclic heterocycle;
in the Formula A-I and the Formula A-III, n≥2, P1 is independently a hydrophilic or water-soluble natural polymer or synthetic polymer;
preferably, for Formula I-1 and Formula I-2, R2, R3, R4, R5 are connected with a carbon atom to form a saturated or unsaturated alicyclic ring or alicyclic heterocycle, or form an aromatic ring or an aromatic heterocyclic ring;
the photoinitiator is a substance capable of generating free radicals under irradiation by light, is selected from a water-soluble photoinitiator and a dispersible photoinitiator, preferably selected from Component B-1, Component B-2, Component B-3, and a derivative of Component B-1, Component B-2 or Component B-3;

20 more elements

Dependencies are inferred from the claim text.

Facts

Application: 16/848,372Filed 14 Apr 2020
Priority: CN 201711132472.215 Nov 2017
Published: 20 Aug 2020
Term ends: Not estimatedThe source records don’t support an estimate.

Classification40 codes

C07D 291/08
Heterocyclic compounds containing rings having nitrogen, oxygen and sulfur atoms as the only ring hetero atoms: condensed with carbocyclic rings…
A61L 24/00
Surgical adhesives or cements
A61L 24/0031
Use of materials characterised by their function or physical properties: hydrogels or hydrocolloids
A61L 24/04
Surgical adhesives or cements; Adhesives for colostomy devices: containing macromolecular materials