Production, raw materials, products and uses of photocrosslinkable hydrogel materials

Abstract

The present invention provides the manufacture, raw materials, products and uses of photocrosslinkable hydrogel materials. [Solution] Component A (photosensitive polymer derivative) is dissolved in a biocompatible medium to obtain photosensitive polymer solution A; component B (photoinitiator) is dissolved in a biocompatible medium to obtain photoinitiator solution B; auxiliary component C (other biocompatible polymer derivative) is dissolved in a biocompatible medium to obtain polymer solution C; solutions A and B (or solution C is added) are homogeneously mixed to obtain a hydrogel precursor solution; and the hydrogel precursor solution is irradiated with a light source to photocrosslink the solution to form a hydrogel. This hydrogel system has advantages such as a fast photocuring rate, strong tissue adhesion, excellent mechanical properties, good biocompatibility, and excellent clinical operability. The present invention also provides a kit for producing hydrogels; uses of the hydrogel material in tissue engineering, regenerative medicine, and 3D printing; and uses of the hydrogel material as a cell, protein, or drug carrier.

Description

[Technical field]

[0001] The present invention relates to the technical field of biomaterials, specifically to the manufacture, raw materials, products and uses of photocrosslinkable hydrogel materials. [Background technology]

[0002] Hydrogels are high-water-content polymeric materials with a three-dimensional network crosslinking structure. They have excellent biocompatibility and certain mechanical strength, and are highly compatible with the microenvironment of biological tissues, and are therefore widely used in tissue engineering and regenerative medicine. In clinical applications, in situ cured hydrogels have excellent tissue shaping ability. Currently, in situ curable hydrogels mainly include temperature-sensitive, two-component injectable, and photosensitive types, etc., depending on the gelation mechanism. The temperature-sensitive type is mainly achieved by reaching the body as a gel precursor that is in a liquid phase at low temperature, and then undergoing phase transition gelation under the action of body temperature to achieve in situ curing (e.g., LeGoom, hydroxybutyl chitosan, etc.). Such hydrogels usually have problems such as weak gel strength, slow temperature response, and slow decomposition in vivo. The two-component injection type mainly achieves in-situ curing by extruding a gel precursor containing an active reactive functional group while mixing it with a two-component syringe (e.g., Fibrin Glue, Adherus AutoSpray, etc.), so there is a very high requirement for the crosslinking speed of the active functional group. If the gelation speed is too slow, the gel precursor may be diluted or washed away by blood or exudate in the body, but if the gelation speed is too fast, it is disadvantageous for clinical operation, the needle tip is easily clogged, and the application cost is high due to the two-component syringe. These defects limit the use of such materials.

[0003] Compared with temperature-sensitive and two-component injectable hydrogels, photosensitive hydrogels have the advantage of being able to precisely control time and space, and therefore have practical clinical operability. In the current photocrosslinking hydrogel manufacturing method, the most common method is to use radicals to initiate polymerization crosslinking of unsaturated biological macromolecules. Although the curing speed by photoradical polymerization is fast (about 2s), the radicals cause damage to cells or biological tissues, and the oxygen accompanying the radicals inhibits polymerization, making it difficult to construct thin hydrogels in situ by this method. In addition, the reduced adhesive ability of such hydrogels to tissues is also an obstacle to the clinical use of this technology. FocalSeal, which is used to prevent hernia formation after lung resection, is the only photosensitive hydrogel approved by the FDA to date. Recently, Biomet has acquired the technology for in situ construction of hydrogels by light from John Hopkins University and is using it to repair cartilage tissue. Although the above technology has a very good clinical effect, when used, it is necessary to use a separate undercoat to promote adhesion of the gel to the tissue, which complicates the clinical application of photosensitive hydrogels.

[0004] In response to the lack of technology for producing hydrogels by photoinitiated radical polymerization crosslinking, Zhu Linyong's research group published a photo-induced non-radical crosslinking technology in 2014 (Yunlong Yang; Jieyuan Zhang; Zhenzhen Liu; Qiuning Lin; Xiaolin Liu; Chunyan Bao; Yang Wang; Linyong Zhu. Adv. Mater. 2016, 28, 2724.;Linyong Zhu et.al. PCT. No.WO2016082725 A1, issued Jun2, 2016). In this technology, O-nitrobenzyl alcohol generates aldehyde groups by ultraviolet irradiation, and crosslinks with polyamino polymer derivatives to produce hydrogel, completely avoiding the generation of radicals, effectively solving the toxicity of radicals and oxygen inhibition, and making it possible to control the thickness of the gel layer. The aldehyde groups generated by O-nitrobenzyl alcohol by light irradiation crosslink with the abundant protein amino acids present on the tissue surface, strengthening the chemical bond between the gel layer and the tissue, thus solving the problems of tissue adhesion and integration of conventional photosensitive hydrogels. However, the gelation speed of this technology is relatively slow, so its clinical application is limited. Summary of the Invention

[0005] A first object of the present invention is to provide a series of photosensitive polymer derivatives. The photosensitive polymer derivative provided by the present invention is 1. A photosensitive polymer derivative modified with an o-nitrobenzyl-based phototrigger having the structure of formula AI (abbreviation: A1); 2. A double bond functional group-containing photosensitive polymer derivative having the structure of formula A-II (abbreviation: A2), and 3. A photosensitive polymer derivative containing both an o-nitrobenzyl-based phototrigger and a double bond functional group, having the structure of formula A-III (abbreviation: A3).

[0006] [ka] The o-nitrobenzyl-based phototrigger has the structural formula I- 1 ofFormula I-1 shows an o-nitrobenzyl-based phototrigger that does not contain a ring structure. 。

[0007] [ka] Formula I- 1 middle When X=O, it is called an o-nitrobenzyl phototrigger, represented by NB. When X=S, it is called an o-nitrobenzylthio phototrigger, represented by sNB. H In this case, it is called an o-nitrobenzylamino-based optical trigger and is expressed in nNb.

[0008] Formula AI, Formula A-III, Formula I, Formula I- 1 middle R' is selected from the group consisting of hydrogen, halogen, hydroxyl group, mercapto group, amino group, nitro group, cyano group, aldehyde group, keto group, ester group, amide group, phosphonic acid group, phosphonate group, sulfonic acid group, sulfonate group, sulfone group, sulfoxide group, aryl group, heteroaryl group, alkyl group, alkylene group, modified alkyl group, modified alkylene group, etc. Formula I- 1 middle R1 is selected from the group consisting of hydrogen, ether-linked substituents, ester-linked substituents, carbonate-linked substituents, urethane-linked substituents, mercaptocarboxylic acid ester-linked substituents, or phosphate ester-linked substituents, and the like; Formula I- 1 middle , R2, R3, R4, and R5 are selected from the group consisting of hydrogen, halogen, hydroxyl group, mercapto group, amino group, nitro group, cyano group, aldehyde group, keto group, carboxyl group, ester group, amide group, phosphonic acid group, phosphonate group, sulfonic acid group, sulfonate group, sulfone group, sulfoxide group, aryl group, heteroaryl group, alkyl group, alkylene group, modified alkyl group, or modified alkylene group, etc.

[0009] Formula I- 1 inIn the depicted structure, R2, R3, R4, and R5 are optionally bonded to each other and together with the carbon atoms to form a saturated or unsaturated aliphatic or heterocyclic ring, or an aromatic or heteroaromatic ring.

[0010] In Formula AI and Formula A-III, n is 2 or more, that is, the average number of o-nitrobenzyl-based phototriggers in one P1 polymer chain is 2 or more.

[0011] In Formula AI and Formula A-III, P1 is a hydrophilic or water-soluble natural or synthetic polymer, or P1 is independently selected from the group consisting of various hydrophilic or water-soluble natural or synthetic polymers, etc.

[0012] In the photosensitive polymer derivative containing a double bond functional group, or the photosensitive polymer derivative containing both an o-nitrobenzyl-based phototrigger and a double bond functional group, R'1, R'2, and R'3 in Formula A-II and Formula A-III are each independently hydrogen, an alkyl group, a modified alkyl group, or an aromatic group. etc. Selected from the group consisting of ;R’ 4 teeth, is selected from the group consisting of alkyl groups, ether-linked substituents, ester-linked substituents, amide-linked substituents, and the like; Where appropriate, in formulae A-II and A-III, R'1, R'2 and R'3 are bonded to each other and together with the carbon atoms form a saturated or unsaturated aliphatic or heterocyclic ring.

[0013] In formula A-II and formula A-III, n is 2 or more, that is, the average number of o-nitrobenzyl-based phototrigger in one P1 polymer chain is 2 or more. P1 is a hydrophilic or water-soluble natural polymer or synthetic polymer, or P1 is independently selected from the group consisting of various hydrophilic or water-soluble natural polymers or synthetic polymers, etc.

[0014] The polymer P1 in the above three types of photosensitive polymer derivatives may be a hydrophilic or water-soluble natural polymer, or a hydrophilic or water-soluble synthetic polymer.

[0015] Hydrophilic or water-soluble natural high molecular weight polymers include natural polysaccharide substances, modified or degraded products thereof, proteins, modified or modified products thereof, and degraded polypeptide substances. The natural polysaccharide materials include hyaluronic acid, carboxymethylcellulose, methylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, alginic acid, glucan, agarose, heparin, chondroitin sulfate, ethylene glycol chitosan, propylene glycol chitosan, chitosan lactate, carboxymethyl chitosan, or chitosan quaternary ammonium salt. The proteins include various hydrophilic or water-soluble animal and plant proteins, collagen, serum proteins, silk fibroin, and elastin, and the decomposition products of the proteins include gelatin or polypeptides. Hydrophilic or water-soluble synthetic polymers include two-arm or multi-arm polyethylene glycols, polyethyleneimines, dendrimers, synthetic polypeptides, polylysine, polyglutamic acid, polyacrylic acid, polymethacrylic acid, polyacrylates, polymethacrylates, polyacrylamides, polymethacrylamides, polyvinyl alcohols, polyvinylpyrrolidones. The above three types of photosensitive polymer derivatives may be hydrophilic or water-soluble polymers containing one or more different groups at the same time, or may be a mixture of hydrophilic or water-soluble polymers containing one or more different groups.

[0016] When component A is a photosensitive polymer derivative modified with an o-nitrobenzyl-based phototrigger having the structure of formula AI, When the o-nitrobenzyl phototrigger has the structure of formula I-1, One end of P1 is bonded to one or more groups selected from R2, R3, R4, and R5; a saturated or unsaturated aliphatic ring or heterocycle formed by R2, R3, R4, and R5; or an aromatic ring or aromatic heterocycle formed by R2, R3, R4, and R5; Sois selected from the group consisting of P1-O- derived from a hydroxyl system, P1-S- derived from a mercapto system, P1-NH- derived from an amino system, P1- derived from an alkane system, P1-COO- derived from an ester system, or P1-CONH- derived from an amide system, one end of said linkage being bonded to P1 and the other end being bonded to the benzene ring of the molecule of formula AI.

[0017] When component A is a photosensitive polymer derivative having both an o-nitrobenzyl-based phototrigger and a double bond functional group having the structure of formula A-III, When the o-nitrobenzyl phototrigger has the structure of formula I-1, One end of P1 is bonded to one or more groups selected from R2, R3, R4, and R5; a saturated or unsaturated aliphatic ring or heterocycle formed by R2, R3, R4, and R5; or an aromatic ring or aromatic heterocycle formed by R2, R3, R4, and R5; the other end of P1 is bound to R'4; So is selected from the group consisting of a hydroxyl-based linkage -O-P1-O-, a mercapto-based linkage -S-P1-S-, an amino-based linkage -NH-P1-NH-, an alkane-based linkage -P1-, an ester-based linkage -COO-P1-COO-, or an amide-based linkage -CONH-P1-CONH-; or the linkage is selected from the group consisting of a hydroxyl-based linkage, a mercapto-based linkage, an amino-based linkage, an alkane-based linkage, an ester-based linkage, and a amide-based linkage having two or more of the hydroxyl-based, mercapto-based, amino-based, alkane-based, ester-based, and amide-based linkages bonded to both ends of P1, one end of the linkage being bonded to P1 and the other end being bonded to the benzene ring of the molecule represented by formula A-III.

[0018] The formula AI is a photosensitive polymer derivative modified with an o-nitrobenzyl-based phototrigger. The formula A-II is a photosensitive polymer derivative containing a double bond functional group. The formula A-III is a photosensitive polymer derivative containing both an o-nitrobenzyl-based phototrigger and a double bond functional group. The structure of formula A-III is designed based on the structures of formula AI and formula A-II, so that an o-nitrobenzyl-based phototrigger and a double bond functional group are simultaneously grafted onto the same polymer chain. This allows two types of crosslinking to be realized simultaneously, that is, it combines the advantages of high speed by photoinitiated radical polymerization crosslinking and strong tissue adhesive force by photocrosslinking reaction, and improves the mechanical performance of the hydrogel by double crosslinking. Therefore, by optimizing the molecular structure, the polymer derivative modified with a photosensitive group shows better material properties, its crosslinking speed is increased from about 30s in the case of simple aldehyde-amino photobond crosslinking to within 2s, the tissue adhesive force is improved to about 80-100kPa, and the mechanical performance is improved to about 1-2MPa. Specific data is provided in Examples 167-169.

[0019] Further, the alkyl group is a saturated or unsaturated aliphatic linear or branched alkyl group having 1-30 carbon atoms; The alkylene group is a saturated or unsaturated aliphatic linear or branched alkylene group having 1-30 carbon atoms; The modified alkyl group is a group in which any carbon atom of an alkyl group is substituted with at least one group selected from the group consisting of a halogen atom, -OH, -SH, -NO2, -CN, -CHO, -COOH, an ester group, an amide group, an aryl group, an arylene group, -CO-, -O-, -S-, -SO-, -SO2-, a primary amino group, a secondary amino group, a tertiary amino group, a quaternary ammonium base, a saturated or unsaturated monocyclic or bicyclic cycloalkylene group, and a bridged aliphatic heterocycle, and the modified alkyl group has 1 to 30 atoms, and the carbon-carbon single bond may be optionally replaced with a carbon-carbon double bond or a carbon-carbon triple bond. The modified alkylene group is an alkylene group in which any carbon atom is substituted with at least one group selected from the group consisting of a halogen atom, -OH, -SH, -NO2, -CN, -CHO, -COOH, an ester group, an amide group, an aryl group, an arylene group, -CO-, -O-, -S-, -SO-, -SO2-, a primary amino group, a secondary amino group, a tertiary amino group, a quaternary ammonium base, a saturated or unsaturated monocyclic or bicyclic cycloalkylene group, and a bridged aliphatic heterocycle, and the modified alkylene group has 1 to 30 atoms, and the carbon-carbon single bond may be optionally replaced with a carbon-carbon double bond or a carbon-carbon triple bond.

[0020] The ether linked substituent is [ka] and the like, where x and y are integers equal to or greater than 0; The ester linked substituent is -CO(CH2) x CH3, -CO(CH2CH2O) x CH3, -CO(CH2) x (CH2CH2O) y CH3, etc., where x and y are integers equal to or greater than 0; The carbonate bonded substituent is -COO(CH2) x CH3, -COO(CH2CH2O) x CH3, -COO(CH2) x (CH2CH2O) y CH3, etc., where x and y are integers equal to or greater than 0; The urethane bonded substituent is -CONH(CH2) x CH3, -CONH(CH2CH2O) x CH3, -CONH(CH2) x (CH2CH2O) y CH3, etc., where x and y are integers equal to or greater than 0; The mercaptocarboxylic acid ester linked substituent is -COS(CH2) x CH3, -COS(CH2CH2O) x CH3, -COS(CH2) x (CH2CH2O) y CH3, where x and y are integers equal to or greater than 0; The phosphate ester linked substituents are -POOO(CH2) x CH3, -POOO(CH2CH2O) x CH3, -POOO(CH2) x (CH2CH2O) y CH3, etc., where x and y are integers equal to or greater than 0; The aryl group is a 5-10 membered aromatic monocyclic or fused bicyclic ring structure; The heteroaryl group is a 5-10 membered aromatic monocyclic or fused bicyclic ring structure containing at least one heteroatom selected from the group consisting of O, S, N or Si on the ring; the halogen atoms are each independently selected from the group consisting of F, Cl, Br, and I; the aliphatic ring is a saturated or unsaturated 3- to 10-membered monocyclic or polycyclic aliphatic ring, the aliphatic heterocycle is a saturated or unsaturated 3- to 10-membered monocyclic or polycyclic aliphatic heterocycle containing at least one heteroatom selected from the group consisting of O, S, N, or Si on the ring, and when the aliphatic heterocycle contains an S atom, it is -S-, -SO-, or -SO2-; H in the aliphatic ring or heterocycle may be optionally substituted with a halogen atom, a nitro group, an aryl group, an alkyl group, or a modified alkyl group; the aromatic ring is a 5- to 10-membered aromatic monocyclic ring or an aromatic condensed bicyclic ring; The aromatic heterocycle is a 5- to 10-membered aromatic monocycle or aromatic condensed bicycle containing at least one heteroatom selected from the group consisting of O, S, N, or Si on the ring, and H in the aromatic ring or aromatic heterocycle may be optionally substituted with a halogen atom, a nitro group, an aryl group, an alkyl group, or a modified alkyl group.

[0021] Further, preferred structures of the aliphatic ring or heterocyclic ring are [ka] etc. Further, preferred structures of the aromatic ring or aromatic heterocycle are [ka] etc. Some preferred structures of R' are: [ka] etc.

[0022] Some preferred structures of R2, R3, R4, and R5 are: Includes -H, -OH, -SH, -NH2, -F, -Cl, -Br, -I, -CF3, -CCl3, -CBr3, -CI3, -NO2, -CN, -CHO, -COOH, -COONH2, -SO3H, etc. A preferred structure of the alkyl group substituent is, for example, a straight chain alkyl group -(CH2) x CH3, branched alkyl group -(CH2) x (CY'Y'') y CH3 (Y', Y'' are hydrogen, an alkyl group, or a modified alkyl group), where x and y are integers of 0 or more; A preferred structure for the ether substituent is, for example, -O(CH2) x CH3, -O(CH2CH2O) x CH3, -O(CH2) x (CH2CH2O) y CH3, etc., where x and y are integers equal to or greater than 0; A preferred structure for the thioether substituent is, for example, -S(CH2) x CH3, -S(CH2CH2O) x CH3, -S(CH2) x (CH2CH2O) y CH3, etc., where x and y are integers equal to or greater than 0; Preferred structures of the amino substituent are, for example, [ka] (Y and Y' are hydrogen, an alkyl group, or a modified alkyl group), where x and y are integers of 0 or more, A preferred structure for the ester substituent is, for example, -COO(CH2) x CH3, -COO(CH2CH2O) x CH3, -COO(CH2) x (CH2CH2O) y CH3, etc., where x and y are integers equal to or greater than 0; A preferred structure for the amide substituent is, for example, -CONH(CH2) x CH3, -CONH(CH2CH2O) x CH3, -CONH(CH2) x (CH2CH2O) y CH3, where x and y are integers equal to or greater than 0; Preferred structures of the aromatic substituent are, for example, [ka] etc.

[0023] The polymer P1 in the polymer derivative modified with an o-nitrobenzyl-based phototrigger may be a hydrophilic or water-soluble natural polymer, including natural polysaccharide substances, modified or decomposed products thereof, proteins, modified or decomposed products thereof, etc. The natural polysaccharide substances include hyaluronic acid, carboxymethylcellulose, methylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, alginic acid, glucan, agarose, heparin, chondroitin sulfate, ethylene glycol chitosan, propylene glycol chitosan, chitosan lactate, carboxymethyl chitosan, chitosan quaternary ammonium salt, etc. The proteins include various hydrophilic or water-soluble animal and plant proteins, collagen, serum protein, silk fibroin, elastin. The protein decomposition products include gelatin or polypeptide, etc. Hydrophilic or water-soluble synthetic polymers include two-arm or multi-arm polyethylene glycols, polyethyleneimines, dendrimers, synthetic polypeptides, polylysine, polyglutamic acid, polyacrylic acid, polymethacrylic acid, polyacrylates, polymethacrylates, polyacrylamides, polymethacrylamides, polyvinyl alcohols, polyvinylpyrrolidones, and the like.

[0024] In the grafted or polymerized water-soluble or hydrophilic polymer derivative, the average number of o-nitrobenzyl-based phototriggers on one polymer chain is 2 or more (ie, n≧2).

[0025] The polymer derivative modified with the o-nitrobenzyl-based phototrigger may be a hydrophilic or water-soluble polymer containing one or more different groups at the same time, or may be a mixture of hydrophilic or water-soluble polymers containing one or more different groups. The hydrophilic or water-soluble polymer refers to a hydrophilic or water-soluble natural polymer or a hydrophilic or water-soluble synthetic polymer.

[0026] Optionally, the polymer derivative modified with the o-nitrobenzyl-based phototrigger of formula AI may be selected from the group consisting of the following structures of component A-1 to component A-50. [ka] [ka] [ka] [ka] [ka] Optionally, the polymer derivative modified with the o-nitrobenzylthio-based phototrigger of formula AI may be selected from the group consisting of the structures of components A-51 to A-69 below. [ka] [ka] Optionally, the polymer derivative modified with the o-nitrobenzylamino-based optical trigger of formula AI may be selected from the group consisting of the structures of components A-70 to A-87 below. [ka] [ka] Growth Component A-1 to Component A- 87 In, n is 2 or more.

[0027] Optionally, the double bond-modified polymer derivative of formula A-II0 may be selected from the group consisting of the structures of components A-107k to A-115 below. [ka] In components A-107 to A-115, n is 2 or more.

[0028] If necessary, the polymer derivative containing both the o-nitrobenzyl-based phototrigger of the formula A-III and the double bond functional group can be prepared by the following components A-116 to A-117. 143 The structure may be selected from the group consisting of: [ka] [ka] Component A-116 to Component A- 143 In the formula, n is 2 or more, HA is hyaluronic acid, CMC is carboxymethylcellulose, Alg is alginic acid, CS is chondroitin sulfate, PGA is polyglutamic acid, PEG is polyethylene glycol, Chitosan is chitosan, Gelatin is gelatin, PLL is polylysine, Dex is glucan, and Hep is heparin.

[0029] Structural formula I- 1 middle, when X=S, it is an o-nitrobenzylthio-based phototrigger, and in the polymer derivative modified with the o-nitrobenzylthio-based phototrigger, the oxygen atom (O) is replaced with a sulfur atom (S). The 3d vacant orbital of the sulfur atom is favorable for intramolecular charge transfer, so the photodecomposition rate and photodecomposition efficiency of the phototrigger are improved, that is, the aldehyde group / keto group or nitroso group can be released more quickly and completely under light irradiation, which increases the crosslinking rate as a crosslinking site, and the released aldehyde group / keto group or nitroso group can be fixed with the bond of the active group on the tissue surface, greatly improving the adhesive force between the material and the tissue. In addition, the simultaneous release and crosslinking of multiple active functional groups (simple aldehyde-amino photobond crosslinking is only the release and crosslinking of a single active functional group) greatly improves the crosslinking efficiency and crosslinking density, and further improves the mechanical performance of the material. Therefore, by optimizing the molecular structure, the polymer derivative modified with photosensitive group shows better material properties, its crosslinking speed is faster than that of simple aldehyde-amino photo-linking of about 30 s to within 2 s, the tissue adhesive force is improved to about 80-100 kPa, and the mechanical performance is improved to about 1-2 MPa. Specific data are shown in Examples 167 to 169.

[0030] Structural formula I- 1 middle , X=N HIn the case of , the phototrigger is an o-nitrobenzylamino-based phototrigger, and in the polymer derivative modified with the o-nitrobenzylamino-based phototrigger, the oxygen atom (O) is replaced with a nitrogen atom (N). The nitrogen atom is a strong electron donor, which is favorable for intramolecular charge transfer, and improves the photodecomposition speed and photodecomposition efficiency of the phototrigger, that is, it can release aldehyde groups / keto groups or nitroso groups more quickly and completely under light irradiation, which increases the crosslinking speed as a crosslinking site, and the released aldehyde groups / keto groups or nitroso groups can be fixed with the binding of active groups on the tissue surface, greatly improving the adhesive strength of the material and tissue. In addition, the simultaneous release and crosslinking of multiple active functional groups (simple aldehyde-amino photobinding crosslinking is only the release and crosslinking of a single active functional group) greatly improves the crosslinking efficiency and crosslinking density, and further improves the mechanical performance of the material. Therefore, by optimizing the molecular structure, the polymer derivative modified with photosensitive group shows better material properties, its crosslinking speed is faster than that of simple aldehyde-amino photo-linking of about 30 s to within 2 s, the tissue adhesive force is improved to about 80-100 kPa, and the mechanical performance is improved to about 1-2 MPa. Specific data are shown in Examples 167 to 169.

[0031] The present invention 2 The object of the present invention is to provide a method for producing a photocrosslinkable hydrogel material. 1 The photosensitive polymer derivative described in the above-mentioned object is used as a raw material.

[0032] The method for producing a photocrosslinkable hydrogel material includes the steps of: Dissolving component A - a photopolymer derivative - in a biocompatible medium to obtain a photopolymer solution A; Dissolving component B-photoinitiator in a biocompatible medium to obtain photoinitiator solution B; uniformly mixing solution A and solution B to obtain a hydrogel precursor solution, and irradiating the hydrogel precursor solution with a light source to form a hydrogel by photocrosslinking. The crosslinking method is that the o-nitrobenzyl-based phototrigger and / or double bond functional group in component A and the component B-photoinitiator respectively generate radical crosslinking (i.e., the radical crosslinking of the o-nitrobenzyl-based phototrigger and the radical crosslinking of the double bond functional group) under light irradiation.

[0033] Further, another method for producing a photocrosslinkable hydrogel material includes the steps of: Dissolving component A - a photopolymer derivative - in a biocompatible medium to obtain a photopolymer solution A; Dissolving component B-photoinitiator in a biocompatible medium to obtain photoinitiator solution B; Dissolving auxiliary component C-other biocompatible polymer derivatives in a biocompatible medium to obtain a polymer solution C, wherein the auxiliary component C-other biocompatible polymer derivatives are polymer derivatives containing amino, hydrazine, acylhydrazine or hydroxylamine functional groups, or polymer derivatives containing mercapto functional groups; and homogeneously mixing solution A, solution B and solution C to obtain a hydrogel precursor solution, and irradiating the hydrogel precursor solution with a light source to form a hydrogel by photocrosslinking. The crosslinking method is that the o-nitrobenzyl-based phototrigger and / or double bond functional group in component A and the component B-photoinitiator respectively generate radical crosslinking under light irradiation (i.e., radical crosslinking of the o-nitrobenzyl-based phototrigger and radical crosslinking of the double bond functional group), and the o-nitrobenzyl-based phototrigger in component A photocrosslinks with the aldehyde group / keto group generated by light irradiation and the amino, hydrazine, acylhydrazine or hydroxylamine functional group in component C, and the generated nitroso group and the mercapto functional group in component C photoinduced nitroso crosslinking, which is a hybrid type of photocrosslinking.

[0034] In the present invention, the hydrogel precursor solution can be selected from component A, component B, and component C according to need. Here, components A and B are essential components, and component C is an auxiliary component, so the hydrogel precursor solution can be component A / component B, or component A / component B / component C. Component A can be selected from photosensitive polymer derivatives A1, A2, and A3 according to need, and can be one of them, or a mixture of one or more photosensitive polymer derivatives (except for the case of A2 alone). Thus, all possible blending methods are A1 / B; A3 / B; A1, A2 / B; A1, A3 / B; A2, A3 / B; A1, A2, A3 / B; A1 / B / C; A3 / B / C; A1, A2 / B / C; A1, A3 / B / C; A2, A3 / B / C; A1, A2, A3 / B / C.

[0035] In the preparation method of the present invention, the biocompatible medium is selected from the group consisting of distilled water, physiological saline, buffer solution and cell culture solution. Different media can be selected according to different applications.

[0036] In the manufacturing method of the present invention, for the hydrogel precursor solution obtained by uniformly mixing, in the case of component A / component B, the concentration of component A may be 0.1%wt-60%wt, but preferably 1%wt-10%wt, the concentration of component B may be 0.01%wt-10%wt, but preferably 0.05%wt-1.0%wt, and the total polymer concentration may be 0.1%wt-60%wt, but preferably 1%wt-10%wt. In the case of component A / component B / component C, the mass ratio of component A to component C may be 1:0.02-50, but preferably 1:0.1-10, the concentration of component B may be 0.01%wt-10%wt, but preferably 0.05%wt-1.0%wt, and the total polymer concentration may be 0.1%wt-60%wt, but preferably 1%wt-10%wt.

[0037] In the preparation method of the present invention, the wavelength of the light source is determined by the absorption wavelength of the o-nitrobenzyl-based phototrigger and the photoinitiator, and may be 250-500 nm, preferably 300-450 nm, more preferably 365, 375, 385, 395, 405 nm.

[0038] The technical principle adopted by the method for producing photocrosslinkable hydrogel of the present invention is as follows: the o-nitrobenzyl-based phototrigger and / or double bond functional group in component A and the photoinitiator in component B each undergo radical crosslinking under light irradiation, while the aldehyde group / keto group generated by the o-nitrobenzyl-based phototrigger in component A undergoes photobond crosslinking with the amino, hydrazine, acylhydrazine or hydroxylamine functional group in component C under light irradiation, and the generated nitroso group and the mercapto functional group in component C undergo photoinduced nitroso crosslinking, thereby achieving multiple crosslinking with only one light irradiation, which is a composite photocrosslinking method.

[0039] In the method for producing a photocrosslinkable hydrogel material, component B-photoinitiator, i.e., a substance capable of generating radicals under light irradiation, is preferably a water-soluble photoinitiator or a photoinitiator dispersible in water, more preferably I 2959 (component B-1), LAP (component B-2), Eosin-Y (component B-3), etc. and their derivatives.

[0040] [ka] Polymer derivatives containing component C-amino, hydrazine, acylhydrazine or hydroxylamine functional groups have the structures of structural formulas CI, C-II, C-III and C-IV, respectively, and polymer derivatives containing mercapto functional groups have the structure of structural formula CV. [ka] In structural formulae CI, C-II, C-III, C-IV, and CV, n is 2 or more, and P2, P3, P4, P5, and P6 may be hydrophilic or water-soluble natural polymers, or may be hydrophilic or water-soluble synthetic polymers, etc.

[0041] Hydrophilic or water-soluble natural high molecular weight polymers include natural polysaccharide substances, modified or degraded products thereof, proteins, modified or modified products thereof, and degraded polypeptide substances.

[0042] The natural polysaccharide materials include hyaluronic acid, carboxymethylcellulose, methylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, alginic acid, glucan, agarose, heparin, chondroitin sulfate, ethylene glycol chitosan, propylene glycol chitosan, chitosan lactate, carboxymethyl chitosan, or chitosan quaternary ammonium salt.

[0043] The proteins include various hydrophilic or water-soluble animal and plant proteins, collagen, serum proteins, silk fibroin, and elastin, and the decomposition products of the proteins include gelatin or polypeptides.

[0044] Hydrophilic or water-soluble synthetic polymers include two-arm or multi-arm polyethylene glycols, polyethyleneimines, dendrimers, synthetic polypeptides, polylysine, polyglutamic acid, poly(meth)acrylic acid, poly(meth)acrylates, poly(meth)acrylamides, polyvinyl alcohol, polyvinylpyrrolidone.

[0045] The polymer derivative containing an amino, hydrazine, acylhydrazine, hydroxylamine or mercapto group may be a hydrophilic or water-soluble natural polymer or synthetic polymer containing one or more different groups at the same time, but may also be a hydrophilic or water-soluble natural polymer or synthetic polymer containing one or more different groups.

[0046] Regarding polymer derivatives containing amino, hydrazine, acylhydrazine, hydroxylamine, etc., the structure represented by formula CI is a water-soluble or hydrophilic polymer containing n amino groups, the structure represented by formula C-II is a water-soluble or hydrophilic polymer containing n hydrazine groups, the structure represented by formula C-III is a water-soluble or hydrophilic polymer containing n acylhydrazine groups, the structure represented by formula C-IV is a water-soluble or hydrophilic polymer containing n hydroxylamine groups, and the structure represented by formula CV is a water-soluble or hydrophilic polymer containing n mercapto groups.

[0047] Optionally, the formula CI is selected from the group consisting of the structures of components C-1 to C-9 below, the formula C-II is selected from the group consisting of the structures of components C-10 below, the formula C-III is selected from the group consisting of the structures of components C-11 to C-13 below, the formula C-IV is selected from the group consisting of the structures of components C-14 to C-15 below, and the formula CV may be selected from the group consisting of the structures of components C-16 to C-21 below. [ka] [ka]

[0048] In components C-1 to C-21, n is 2 or more, component C-1 is chitosan, component C-2 is ethylene glycol chitosan, component C-3 is carboxymethyl chitosan, component C-4 is gelatin, component C-5 is polylysine, component C-6 is polyethyleneimine, component C-7 is 2-arm amino polyethylene glycol, component C-8 is 4-arm amino polyethylene glycol, component C-9 is an amino polymer, component C-10 is hydrazine-modified carboxymethyl cellulose, and components C-11 to C-13 are acyl C-15 is a glucan modified with hydroxylamine, C-16 is a 2-arm mercaptopolyethylene glycol, C-17 is a 4-arm mercaptopolyethylene glycol, C-18 is a hyaluronic acid modified with a mercapto group, C-19 is a chitosan modified with a mercapto group, C-20 is a glucan modified with a mercapto group, and C-21 is a heparin modified with a mercapto group.

[0049] The present invention 3 The object of the invention is to 2 The object of the present invention is to provide a product produced by the method for producing a photocrosslinkable hydrogel material described above, i.e., a photocrosslinkable hydrogel material (also called a hybrid photocrosslinkable hydrogel material).

[0050] The present invention 4 It is an object of the present invention to provide a kit for use in producing a hydrogel according to the method of the present invention.

[0051] The first kit includes Component A - a photopolymer derivative, Component B - a photoinitiator, and instructions for making and using the hydrogel. Here, component A-photosensitive polymer derivative is 1. A photosensitive polymer derivative modified with an o-nitrobenzyl-based phototrigger having the structure of formula AI (abbreviation: A1); and 2. A photosensitive polymer derivative (abbreviation: A3) containing both an o-nitrobenzyl-based phototrigger and a double bond functional group, which has the structure of formula A-III.

[0052] The o-nitrobenzyl-based phototrigger has the structural formula I- 1 of Structural formula I-1 shows an o-nitrobenzyl-based phototrigger that does not contain a cyclic structure. In formula I-1 When X=O, it is called an o-nitrobenzyl-based phototrigger, represented by NB. When X=S, it is called an o-nitrobenzylthio-based phototrigger, represented by sNB. H In the case of nN, it is called an o-nitrobenzylamino-based optical trigger. B It is expressed as:

[0053] Component B--photoinitiator, i.e., a substance capable of generating radicals under irradiation with light, is preferably a water-soluble photoinitiator or a photoinitiator dispersible in water, more preferably I 2959 (component B-1), LAP (component B-2), Eosin-Y (component B-3), etc. and their derivatives.

[0054] In addition to the components of the first kit, the second kit contains a photosensitive polymer derivative containing a double bond functional group as component A-photosensitive polymer derivative of the first kit. The photosensitive polymer derivative containing a double bond functional group (abbreviation: A2) has the structure of the above formula A-II.

[0055] The third kit further includes an auxiliary component C in addition to the first kit. The auxiliary component C is another biocompatible polymer derivative, including a polymer derivative containing an amino, hydrazine, acylhydrazine, hydroxylamine or mercapto functional group. The definition of the auxiliary component C is as follows: 2 This is the same as auxiliary component C in the method for producing a photocrosslinkable hydrogel material described in the above item 1.

[0056] The fourth kit further includes an auxiliary component C under the second kit. The auxiliary component C is another biocompatible polymer derivative, including a polymer derivative containing an amino, hydrazine, acylhydrazine, hydroxylamine or mercapto functional group. The definition of the auxiliary component C is as follows: 2 This is the same as auxiliary component C in the method for producing a photocrosslinkable hydrogel material described in the above item 1.

[0057] The above four types of kits may further include a biocompatible medium, such as distilled water, physiological saline, buffer, and cell culture medium.

[0058] Uses of the hydrogels described in the instructions for these four kits include post-operative wound closure, tissue leak sealing, hemostatic materials, tissue engineering scaffold materials, use in bioinks for 3D printing, and as cell, protein or drug carriers.

[0059] The present invention 5 The object of the present invention is to provide a use of a product produced by the method for producing a photocrosslinkable hydrogel material, i.e., a photocrosslinkable hydrogel.

[0060] The present invention provides the use of said photocrosslinkable hydrogel in the manufacture of postoperative wound closure-skin repair materials or drugs.

[0061] The present invention further provides a use of said photocrosslinkable hydrogel in the manufacture of a postoperative wound closure-postoperative adhesion prevention material or drug.

[0062] The present invention further provides a use of said photocrosslinkable hydrogel in the manufacture of a post-operative wound closure-oral ulcer material or medicament.

[0063] The present invention further provides a use of said photocrosslinkable hydrogel in the manufacture of tissue fluid leak sealant-gut wall leak sealant or drug.

[0064] The present invention further provides the use of said photocrosslinkable hydrogel in the manufacture of tissue fluid leak sealing-surgical suture material or drug.

[0065] The present invention further provides the use of said photocrosslinkable hydrogel in the manufacture of a hemostatic material-liver hemostatic material or drug.

[0066] The present invention further provides a use of said photocrosslinkable hydrogel in the manufacture of a hemostatic material-bone cross-section hemostatic material or drug.

[0067] The present invention further provides the use of said photocrosslinkable hydrogel in the manufacture of a hemostatic material - an arterial hemostatic material or a medicament.

[0068] The present invention further provides the use of said photocrosslinkable hydrogel in the manufacture of a hemostatic material-cardiac hemostatic material or drug.

[0069] The present invention further provides the use of said photocrosslinkable hydrogel in the manufacture of a tissue engineering scaffold material-cartilage repair material or a drug.

[0070] The present invention further provides the use of said photocrosslinkable hydrogel in the manufacture of a tissue engineering scaffold material-bone repair material or a drug.

[0071] The present invention further provides a use of said photocrosslinkable hydrogel in the manufacture of a tissue engineering scaffold material-bone / cartilage composite defect repair material or drug.

[0072] The present invention further provides the use of said photocrosslinkable hydrogel in a 3D printing (FDM) material - bioink.

[0073] The present invention further provides the use of said photocrosslinkable hydrogel in 3D printing (DLP) materials - bioinks.

[0074] The present invention further provides the use of said photocrosslinkable hydrogel in the preparation of cell, protein, and drug carriers.

[0075] In the present invention, the formula AI is a photosensitive polymer derivative modified with an o-nitrobenzyl-based phototrigger, the formula A-II is a photosensitive polymer derivative containing a double bond functional group, and the formula A-III is a photosensitive polymer derivative containing both an o-nitrobenzyl-based phototrigger and a double bond functional group. Component A is composed of one or more photosensitive polymer derivatives of formula AI, formula A-II, and formula A-III, and component A-photosensitive polymer derivative is dissolved in a biocompatible medium to obtain a photosensitive polymer solution A. Component B-photoinitiator is dissolved in a biocompatible medium to obtain a photoinitiator solution B. Auxiliary component C-other biocompatible polymer derivatives are dissolved in a biocompatible medium to obtain a polymer solution C. Solution A and solution B (or solution C is further added) are uniformly mixed to obtain a hydrogel precursor solution. The hydrogel precursor solution is irradiated with a light source to generate photocrosslinking to form a hydrogel. The crosslinking method includes the following two types.

[0076] Method 1: Solution A and solution B are mixed uniformly to obtain a hydrogel precursor solution, and the hydrogel precursor solution is irradiated with a light source to form a hydrogel by photocrosslinking. The crosslinking method is that the o-nitrobenzyl-based phototrigger and / or double bond functional group in component A and the component B-photoinitiator respectively generate radical crosslinking under light irradiation (i.e., radical crosslinking of the o-nitrobenzyl-based phototrigger and radical crosslinking of the double bond functional group). The radical crosslinking of the o-nitrobenzyl-based phototrigger is that the nitroso group generated by o-nitrobenzyl under light irradiation captures the photoinitiator, and generates a nitroso radical with extremely strong activity under light irradiation, which can be dimerized and crosslinked by itself, and can also be added and crosslinked with other active groups in component A (e.g., mercapto group, hydroxyl group, aminocarboxyl group, sulfonic acid group, carbonyl group, double bond, etc.) to form a hydrogel. The reaction activity of the nitroso radical is higher than that of a simple nitroso group, which can further improve the crosslinking speed and crosslinking efficiency of the hydrogel. The radical crosslinking of the double bond functional group is that the radical generated by the photoinitiator under light irradiation is transferred to the double bond, and the crosslinking of the double bond is initiated. The above two radical crosslinking methods may be performed only one crosslinking (i.e., using the photosensitive polymer derivative represented by formula AI or formula A-II of component A), or may be performed simultaneously under one light irradiation (i.e., using the photosensitive polymer derivative represented by formula A-III of component A alone, or using two or more photosensitive polymer derivatives of formula AI, formula A-II, and formula A-III simultaneously). Such a photocrosslinking method is a multiple crosslinking that combines the advantages of high speed due to photoinitiated radical polymerization crosslinking and strong tissue adhesive strength due to o-nitrobenzyl-based phototriggered crosslinking, and therefore can further improve the mechanical performance of the hydrogel. The crosslinking speed is increased from about 30s in the case of simple aldehyde-amino photobond crosslinking to within 2s, the tissue adhesive strength is improved to about 80-100kPa, and the mechanical performance is improved to about 1-2MPa. Specific data is provided in Examples 167-169.

[0077] Method 2: First, solution A, solution B and solution C are mixed uniformly to obtain a hydrogel precursor solution, and the hydrogel precursor solution is irradiated with a light source to perform photocrosslinking to form a hydrogel. The crosslinking method is that the o-nitrobenzyl-based phototrigger and / or double bond functional group in component A and the component B-photoinitiator respectively generate radical crosslinking (i.e., radical crosslinking of the o-nitrobenzyl-based phototrigger and radical crosslinking of the double bond functional group) under light irradiation. Regarding the radical crosslinking of the o-nitrobenzyl-based phototrigger, the nitroso group generated by o-nitrobenzyl under light irradiation captures the photoinitiator, and generates a nitroso radical with extremely strong activity under light irradiation, which can itself dimerize and crosslink, and can also form a hydrogel by addition crosslinking with other active groups in component A (e.g., mercapto group, hydroxyl group, aminocarboxyl group, sulfonic acid group, carbonyl group, double bond, etc.). Since the reaction activity of the nitroso radical is higher than that of a simple nitroso group, the crosslinking speed and crosslinking efficiency of the hydrogel can be further improved. The radical crosslinking of the double bond functional group is that the radical generated by the photoinitiator under light irradiation is transferred to the double bond, and the crosslinking of the double bond is initiated. In addition, the aldehyde group / keto group generated by the o-nitrobenzyl-based phototrigger in component A undergoes Schiff base crosslinking with the amino, hydrazine, acylhydrazine or hydroxylamine functional group in component C, and the generated nitroso group undergoes photoinduced nitroso crosslinking with the mercapto functional group in component C. The above two radical crosslinking methods may perform only one crosslinking (i.e., using the photosensitive polymer derivative represented by formula AI or formula A-II in component A), or may be performed simultaneously under one light irradiation (i.e., using the photosensitive polymer derivative represented by formula A-III in component A alone, or using two or more photosensitive polymer derivatives of formula AI, formula A-II, and formula A-III simultaneously). This photocrosslinking method is a multi-crosslinking method that combines the advantages of high speed due to photoinitiated radical polymerization crosslinking and strong tissue adhesion due to o-nitrobenzyl-based phototriggered crosslinking, and therefore can further improve the mechanical performance of the hydrogel.The crosslinking speed is increased from about 30 s in the case of simple aldehyde-amino photo-crosslinking to within 2 s, the tissue adhesive strength is improved to about 80-100 kPa, and the mechanical performance is improved to about 1-2 MPa. Specific data are shown in Examples 167 to 169.

[0078] The following formula is a schematic diagram of crosslinking of the photocrosslinkable hydrogel. [ka] In the present invention, such photocrosslinkable hydrogel is a new photocrosslinkable gel technology developed based on the conventional photocrosslinking method (i.e., simple aldehyde-amino photobond crosslinking or photoinitiated radical polymerization crosslinking). By introducing component B-photoinitiator, the crosslinking speed and crosslinking efficiency of the conventional o-nitrobenzyl-based phototrigger (crosslinking by generating nitroso radicals with extremely high reaction activity) can be improved, and a composite photosensitive polymer solution can be formed by mixing a polymer derivative of photoinitiated radical polymerization crosslinking and a polymer derivative of photocrosslinking reaction, and the initiator can be activated by a single light irradiation to generate radicals, thereby performing radical crosslinking (i.e., radical crosslinking of o-nitrobenzyl-based phototrigger and radical crosslinking of double bond functional groups). Furthermore, multiple photocrosslinking can be achieved by photocrosslinking reactions (i.e., Schiff base crosslinking between the aldehyde group / keto group generated by the o-nitrobenzyl-based phototrigger under light irradiation and the amino, hydrazine, acylhydrazine, or hydroxylamine functional group in component C) and photoinduced nitroso crosslinking (i.e., photoinduced nitroso crosslinking between the nitroso group generated by the o-nitrobenzyl-based phototrigger under light irradiation and the mercapto functional group in component C), allowing the production of composite hydrogels.

[0079] The present invention has the following advantages over the prior art: (1) The photocuring speed is fast, reaching the gel point in 1-2 s and the final elastic modulus in 10-20 s, and multiple photocrosslinking is achieved in one go, so its photocuring speed is superior to that of simple photoinitiated radical polymerization crosslinking and photobonding crosslinking. (2) It has strong tissue adhesion and can gel in situ on the tissue surface. In addition, the aldehyde / keto and nitroso groups generated by light irradiation react with the mercapto and aminocarboxyl groups on the tissue surface, chemically bonding the hydrogel to the surrounding tissue and fusing them together, thus solving the problem that a separate undercoat is required for radical polymerization crosslinking. (3) It has excellent mechanical properties and good ductility and strength, which solves the problem that most conventional hydrogels have poor mechanical properties and are easily broken. (4) It has good biocompatibility, the raw materials are mainly derived from natural polymer materials, and the formed hydrogel is degradable. (5) Convenient clinical operation: Photocrosslinking has excellent time and space controllability, so when used, the hydrogel precursor solution can be painted or sprayed onto the wound tissue, where it can gel rapidly under light irradiation and fuse with the tissue, eliminating the need for a primer and realizing wound closure in one step. (6) The chemical structure, composition, degradability, strength and thickness of the gel can be adjusted, and the composition and properties of the gel material can be adjusted according to the purpose of use. In particular, a thin gel can be formed in situ at the wound surface, which can be used for postoperative wound closure and repair, and tissue leakage sealing, as well as for use as a hemostatic material and tissue engineering scaffold material, and can also be used in bioink for 3D printing. It can also provide an in situ carrier for cells, proteins or drugs, and can be effectively used in regenerative medicine.

[0080] Therefore, the technical means of the photocrosslinkable hydrogel system can facilitate the clinical application of photoin-situ gel technology. [Brief description of the drawings]

[0081] Note: NB is an o-nitrobenzyl-based phototrigger in component A-1 of the present invention, cNB is a cyclic o-nitrobenzyl-based phototrigger in component A-88 of the present invention, and cNB-MA is an o-nitrobenzyl-based phototrigger containing both a cyclic o-nitrobenzyl-based phototrigger and a double bond functional group in component A-144 of the present invention. Here, HA-NB is component A-1, HA-cNB is component A-88, and HA-cNB-MA is component A-144. [Figure 1] 1 shows real-time rheograms of gelation of hydrogel precursor solutions (2% HA-NB / 6% gelatin / 1% HAMA / 0.2% LAP or 2% HA-cNB / 1% HA-cNB-MA / 0.2% LAP) upon irradiation with light. [Diagram 2] FIG. 1 shows an adhesive strength test of hydrogels (2% HA-NB / 6% gelatin / 1% HAMA / 0.2% LAP or 2% HA-cNB / 1% HA-cNB-MA / 0.2% LAP). [Diagram 3] FIG. 1 shows a compression test of hydrogels (2% HA-NB / 6% gelatin / 1% HAMA / 0.2% LAP or 2% HA-cNB / 1% HA-cNB-MA / 0.2% LAP). [Figure 4] FIG. 1 shows a biocompatibility test of the hydrogels (HA-NB / Gelatin / HAMA / LAP or HA-cNB / HA-cNB-MA / LAP). [Diagram 5] FIG. 1 is a graph showing the effect of hydrogel (component A-1 / component A-107 / component C-4 / component B-2) on wound closure. [Figure 6] FIG. 1 is a graph showing the effect of hydrogel (component A-1 / component A-107 / component C-4 / component B-2) in preventing postoperative adhesion. [Figure 7] FIG. 1 is a graph showing the effect of hydrogel (component A-1 / component A-107 / component C-4 / component B-2) on hemostasis in the liver. [Figure 8] FIG. 1 is a graph showing the effect of a hydrogel (component A-1 / component A-107 / component C-4 / component B-2) bone / cartilage tissue engineering scaffold material. [Figure 9] FIG. 13 is a print effect diagram of a bioink of hydrogel (component A-1 / component A-107 / component C-4 / component B-2). DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0082] The present invention will be further described below with reference to the following examples. The present invention will be further described below with reference to the following figures and examples. However, these examples are merely illustrative of the best mode for carrying out the present invention and are not intended to limit the scope of the present invention. Any other changes and modifications made by those skilled in the art without departing from the spirit and scope of the present invention are within the scope of the present invention.

[0083] Example 1: Synthesis of Component A-1 [ka] (1) Synthesis of Compound 1: The synthesis is carried out according to the method disclosed in the reference Yunlong Yang; Jieyuan Zhang; Zhenzhen Liu; Qiuning Lin; Xiaolin Liu; Chunyan Bao; Yang Wang; Linyong Zhu. Adv. Mater. 2016, 28, 2724. 1 H NMR (400mHz, CDCl3): δ=7.71 (s, 1H), 7.22 (s, 1H), 4.96 (s, 2H), 4.13 (t, J=6.1 Hz, 2H), 3.99 (s, 3H), 3.32 (dd, J=11.6, 5.7 Hz, 2H), 2.82 (t, J=5.9 Hz, 2H), 2.44 (t, J=7.2 Hz, 2H), 2.26 - 2.17 (m, 2H). MS (ESI): [M+H] 328.1507. (2) Synthesis of component A-1: ​​Hyaluronic acid (2 g, 340 kDa) was dissolved in 100 mL 0.01 mol / L 2-(N-morpholine)ethanesulfonic acid MES buffer solution (pH = 5.2), stirred until completely dissolved, compound 1 (65 mg, 0.2 mmol) was weighed and dissolved in 10 mL dimethyl sulfoxide DMSO, and then added to the reaction solution, 4-(4,6-dimethoxytriazin-2-yl)-4-methylmorpholine hydrochloride DMTMM (0.4 g, 1.5 mmol) was weighed and dissolved in 3 mL MES buffer solution, and added to the reaction solution three times (once every hour), and reacted at 35 ° C for 24 hours. After that, the reaction solution was placed in a dialysis bag (MWCO 7000), dialyzed with deionized water for 2-3 days, and freeze-dried to obtain photosensitive hyaluronic acid derivative A-1 (1.85 g). 1 The labeling rate of compound 1 calculated based on the H-NMR spectrum was approximately 3.42%.

[0084] Example 2: Synthesis of Component A-2 [ka] (1) Synthesis of Compound 2: The compound is synthesized according to the method disclosed in the references James F. Cameron.; Jean MJ Frechet. J. Am. Chem. Soc. 1991, 113, 4303.

[0085] (2) Synthesis of Compound 3: Compound 2 (1 g, 3.2 mmol) and ethylenediamine (1.1 mL) were dissolved in methanol (50 mL) and reacted under reflux overnight, then rotary evaporated under reduced pressure, the crude product was dissolved in methanol and reprecipitated in ethyl acetate. After multiple dissolution-reprecipitation cycles, the product was filtered and dried in vacuum to obtain Compound 3 (0.89 g, 82% yield). 1H NMR (400mHz, CDCl3): δ=7.71 (s, 1H), 7.22 (s, 1H),4.96 (m, 1H), 4.13 (t, J=6.1 Hz, 2H), 3.99 (s, 3H), 3.32 (dd, J=11.6, 5.7 Hz, 2H), 2.82 (t, J=5.9 Hz, 2H), 2.44 (t, J=7.2 Hz, 2H), 2.26 - 2.17 (m, 2H), 1.33 (d, J=6.9 Hz, 3H). MS (ESI): [M+H] 342.1624. (3) Synthesis of component A-2: Hyaluronic acid (2g, 340kDa) was dissolved in 100mL 0.01mol / L 2-(N-morpholine)ethanesulfonic acid MES buffer solution (pH=5.2), stirred until completely dissolved, compound 3 (68mg, 0.2mmol) was weighed and dissolved in 10mL dimethylsulfoxide DMSO, then added to the reaction solution, 4-(4,6-dimethoxytriazin-2-yl)-4-methylmorpholine hydrochloride DMTMM (0.4g, 1.5mmol) was weighed and dissolved in 3mL MES buffer solution, added to the reaction solution three times (once every hour), and reacted at 35°C for 24 hours. After that, the reaction solution was placed in a dialysis bag (MWCO 7000), dialyzed with deionized water for 2-3 days, and freeze-dried to obtain photosensitive hyaluronic acid derivative A-2 (1.92g). 1 The labeling rate of compound 3 calculated based on the H-NMR spectrum was approximately 3.29%.

[0086] Example 3: Synthesis of component A-3 [ka] (1) Synthesis of Compound 4: The compound is synthesized according to the method disclosed in the reference Michael C. Pirrung.; Yong Rok Lee.; Kaapjoo.; James B. Springer. J. Org. Chem. 1999, 64, 5042.

[0087] (2) Synthesis of Compound 5: Compound 4 (1 g, 2.7 mmol) and ethylenediamine (1.1 mL) were dissolved in methanol (50 mL) and reacted under reflux overnight. The mixture was then rotary evaporated under reduced pressure, and the crude product was dissolved in methanol and reprecipitated in ethyl acetate. After multiple dissolution-reprecipitation cycles, the product was filtered and dried in vacuum to obtain Compound 5 (0.80 g, 74% yield). 1 H NMR (400mHz, CDCl3): δ=7.71 (s, 1H), 7.22 (s, 1H), 6.35 (dd, J=10.0, 15.0 Hz, 1H), 6.04 (m, 1H), 5.8 (m, 1H), 5.4 (m, 1H), 4.96 (m, 1H), 4.13 (t, J=6.1 Hz, 2H), 3.99 (s, 3H), 3.32 (dd, J=11.6, 5.7 Hz, 2H), 2.82 (t, J=5.9 Hz, 2H), 2.44 (t, J=7.2 Hz, 2H), 2.26 - 2.17 (m, 2H), 1.75 (d, J=6.5 Hz, 3H). MS (ESI): [M+H] 394.1908. (3) Synthesis of component A-3: Hyaluronic acid (2g, 340kDa) was dissolved in 100mL 0.01mol / L 2-(N-morpholine)ethanesulfonic acid MES buffer solution (pH=5.2), stirred until completely dissolved, compound 5 (79mg, 0.2mmol) was weighed and dissolved in 10mL dimethylsulfoxide DMSO, then added to the reaction solution, 4-(4,6-dimethoxytriazin-2-yl)-4-methylmorpholine hydrochloride DMTMM (0.4g, 1.5mmol) was weighed and dissolved in 3mL MES buffer solution, added to the reaction solution three times (once every hour), and reacted at 35°C for 24 hours. After that, the reaction solution was placed in a dialysis bag (MWCO 7000), dialyzed with deionized water for 2-3 days, and freeze-dried to obtain photosensitive hyaluronic acid derivative A-3 (1.73g). 1 The labeling rate of compound 5 calculated based on the H-NMR spectrum was approximately 2.97%.

[0088] Example 4: Synthesis of Component A-4 [ka] (1) Synthesis of Compound 6: The compound is synthesized according to the method disclosed in the references Isabelle Aujard.; Chouaha Benbrahim.; Ludovic Jullien. Chem. Eur. J. 2006, 12, 6865.

[0089] (2) Synthesis of Compound 7: Compound 6 (1 g, 3.1 mmol) and ethylenediamine (1.1 mL) were dissolved in methanol (50 mL) and reacted under reflux overnight. The mixture was then rotary evaporated under reduced pressure, and the crude product was dissolved in methanol and reprecipitated in ethyl acetate. After multiple dissolution-reprecipitation cycles, the product was filtered and dried in vacuum to obtain Compound 7 (0.85 g, 78% yield). 1 H NMR (400mHz, CDCl3): δ=7.71 (s, 1H), 7.22 (s, 1H), 4.96 (s, 1H), 4.13 (t, J=6.1 Hz, 2H), 3.99 (s, 3H), 3.32 (dd, J=11.6, 5.7 Hz, 2H), 2.82 (t, J=5.9 Hz, 2H), 2.44 (t, J=7.2 Hz, 2H), 2.26 - 2.17 (m, 2H). MS (ESI): [M+H] 353.1426. (3) Synthesis of component A-4: Hyaluronic acid (2g, 340kDa) was dissolved in 100mL 0.01mol / L 2-(N-morpholine)ethanesulfonic acid MES buffer solution (pH=5.2), stirred until completely dissolved, compound 7 (70mg, 0.2mmol) was weighed and dissolved in 10mL dimethylsulfoxide DMSO, then added to the reaction solution, 4-(4,6-dimethoxytriazin-2-yl)-4-methylmorpholine hydrochloride DMTMM (0.4g, 1.5mmol) was weighed and dissolved in 3mL MES buffer solution, added to the reaction solution three times (once every hour), and reacted at 35°C for 24 hours. After that, the reaction solution was placed in a dialysis bag (MWCO 7000), dialyzed with deionized water for 2-3 days, and freeze-dried to obtain photosensitive hyaluronic acid derivative A-4 (1.78g). 1 The labeling rate of compound 7 calculated based on the H-NMR spectrum was approximately 2.49%.

[0090] <Example 5> Synthesis of Component A-5 [ka] (1) Synthesis of compound 8: The compound is synthesized according to the method disclosed in the references Alexander G. Russell.; Dario M. Bassani.; John S. Snaith. J. Org. Chem. 2010, 75, 4648.

[0091] (2) Synthesis of Compound 9: Compound 8 (1 g, 2.9 mmol) and ethylenediamine (1.1 mL) were dissolved in methanol (50 mL) and reacted under reflux overnight. The mixture was then rotary evaporated under reduced pressure, and the crude product was dissolved in methanol and reprecipitated in ethyl acetate. After multiple dissolution-reprecipitation cycles, the product was filtered and dried in vacuum to obtain Compound 9 (0.78 g, 72% yield). 1H NMR (400mHz, CDCl3): δ=7.71 (s, 1H), 7.22 (s, 1H), 4.96 (s, 1H), 4.13 (t, J=6.1 Hz, 2H), 3.99 (s, 3H), 3.32 (dd, J=11.6, 5.7 Hz, 2H), 2.82 (t, J=5.9 Hz, 2H), 2.44 (t, J=7.2 Hz, 2H), 2.26 - 2.17 (m, 2H). MS (ESI): [M+H] 372.1424. (3) Synthesis of component A-5: Hyaluronic acid (2g, 340kDa) was dissolved in 100mL 0.01mol / L 2-(N-morpholine)ethanesulfonic acid MES buffer solution (pH=5.2), stirred until completely dissolved, compound 9 (74mg, 0.2mmol) was weighed and dissolved in 10mL dimethylsulfoxide DMSO, then added to the reaction solution, 4-(4,6-dimethoxytriazin-2-yl)-4-methylmorpholine hydrochloride DMTMM (0.4g, 1.5mmol) was weighed and dissolved in 3mL MES buffer solution, added to the reaction solution three times (once every hour), and reacted at 35°C for 24 hours. After that, the reaction solution was placed in a dialysis bag (MWCO 7000), dialyzed with deionized water for 2-3 days, and freeze-dried to obtain photosensitive hyaluronic acid derivative A-5 (1.76g). 1 The labeling rate of compound 9 calculated based on the H-NMR spectrum was approximately 3.08%.

[0092] Example 6: Synthesis of Component A-6 [ka] (1) Synthesis of Compound 10: The compound is synthesized according to the method disclosed in the references Alexandre Specht.; Maurice Goeldner. Angew. Chem. Int. Ed. 2004, 43, 2008.

[0093] (2) Synthesis of Compound 11: Compound 10 (1 g, 2.7 mmol) and ethylenediamine (1.1 mL) were dissolved in methanol (50 mL) and reacted under reflux overnight. The mixture was then rotary evaporated under reduced pressure, and the crude product was dissolved in methanol and reprecipitated in ethyl acetate. After multiple dissolution-reprecipitation cycles, the product was filtered and dried in vacuum to obtain Compound 11 (0.68 g, 63% yield). 1 H NMR (400mHz, CDCl3): δ=7.71 (s, 1H), 7.22 (s, 1H), 4.96 (s, 1H), 4.13 (t, J=6.1 Hz, 2H), 3.99 (s, 3H), 3.32 (dd, J=11.6, 5.7 Hz, 2H), 2.82 (t, J=5.9 Hz, 2H), 2.44 (t, J=7.2 Hz, 2H), 2.26 - 2.17 (m, 2H). MS (ESI): [M+H] 396.1374. (3) Synthesis of component A-6: Hyaluronic acid (2g, 340kDa) was dissolved in 100mL 0.01mol / L 2-(N-morpholine)ethanesulfonic acid MES buffer (pH=5.2), stirred until completely dissolved, compound 11 (79mg, 0.2mmol) was weighed and dissolved in 10mL dimethylsulfoxide DMSO, then added to the reaction solution, 4-(4,6-dimethoxytriazin-2-yl)-4-methylmorpholine hydrochloride DMTMM (0.4g, 1.5mmol) was weighed and dissolved in 3mL MES buffer, added to the reaction solution three times (once every hour), and reacted at 35°C for 24 hours. After that, the reaction solution was placed in a dialysis bag (MWCO 7000), dialyzed with deionized water for 2-3 days, and freeze-dried to obtain photosensitive hyaluronic acid derivative A-6 (1.79g). 1 The labeling rate of compound 11 calculated based on the H-NMR spectrum was approximately 2.34%.

[0094] <Example 7> Synthesis of Component A-7 [ka] (1) Synthesis of Compound 12: The compound is synthesized according to the method disclosed in the references Jack E. Baldwin.; Adrian W. McConnaughie.; Sung Bo Shin. Tetrahedron. 1990, 46, 6879.

[0095] (2) Synthesis of Compound 13: Compound 12 (1 g, 2.4 mmol) and ethylenediamine (1.1 mL) were dissolved in methanol (50 mL) and reacted under reflux overnight. The mixture was then rotary evaporated under reduced pressure, and the crude product was dissolved in methanol and reprecipitated in ethyl acetate. After multiple dissolution-reprecipitation cycles, the product was filtered and dried in vacuum to obtain Compound 13 (0.61 g, 57% yield). 1 H NMR (400mHz, CDCl3): δ=7.71 (s, 1H),7.75 (ddd, J=8.2, 1.4, 0.4 Hz, 1H), 7.22 (s, 1H), 7.57 (tdd, J=7.3, 1.4, 0.7 Hz, 1H), 7.49 (dd, J=7.9, 1.4 Hz, 1H), 7.36 (ddd, J=8.1, 7.3, 1.4 Hz, 1H), 4.96 (s, 1H), 4.13 (t, J=6.1 Hz, 2H), 3.99 (s, 3H), 3.32 (dd, J=11.6, 5.7 Hz, 2H), 2.82 (t, J=5.9 Hz, 2H), 2.44 (t, J=7.2 Hz, 2H), 2.26 - 2.17 (m, 2H). MS (ESI): [M+H] 449.1618. (3) Synthesis of component A-7: Hyaluronic acid (2g, 340kDa) was dissolved in 100mL 0.01mol / L 2-(N-morpholine)ethanesulfonic acid MES buffer (pH=5.2), stirred until completely dissolved, compound 13 (90mg, 0.2mmol) was weighed and dissolved in 10mL dimethylsulfoxide DMSO, then added to the reaction solution, 4-(4,6-dimethoxytriazin-2-yl)-4-methylmorpholine hydrochloride DMTMM (0.4g, 1.5mmol) was weighed and dissolved in 3mL MES buffer, added to the reaction solution three times (once every hour), and reacted at 35°C for 24 hours. After that, the reaction solution was placed in a dialysis bag (MWCO 7000), dialyzed with deionized water for 2-3 days, and freeze-dried to obtain photosensitive hyaluronic acid derivative A-7 (1.72g). 1 The labeling rate of compound 13 calculated based on the H-NMR spectrum was approximately 2.38%.

[0096] <Example 8> Synthesis of Component A-8 [ka] (1) Synthesis of compound 14: Synthesis is performed according to the method disclosed in the references Pauloehrl, T.; Delaittre, G.; Bruns, M.; Meiβler, M.; Bοrner, HG; Bastmeyer, M.; Barner-Kowollik, C. Angew. Chem. Int. Ed. 2012, 51, 9181.

[0097] (2) Synthesis of Compound 15: Compound 14 (1 g, 2.6 mmol) and ethylenediamine (1.1 mL) were dissolved in methanol (50 mL) and reacted under reflux overnight. The mixture was then rotary evaporated under reduced pressure, and the crude product was dissolved in methanol and reprecipitated in ethyl acetate. After multiple dissolution-reprecipitation cycles, the product was filtered and dried in vacuum to obtain Compound 15 (0.90 g, 83% yield). 1H NMR (400mHz, CDCl3): δ=7.71 (s, 1H), 7.22 (s, 1H), 4.96 (s, 2H), 4.13 (t, J=6.1 Hz, 2H), 3.99 (s, 3H), 3.90 - 3.80 (m, 1H), 3.63 - 3.52(m, 1H), 3.32 (dd, J=11.6, 5.7 Hz, 2H), 2.82 (t, J=5.9 Hz, 2H), 2.44 (t, J=7.2 Hz, 2H), 2.26 - 2.17 (m, 2H), 2.00 - 1.34 (m, 6H). MS (ESI): [M+H] 412.2027. (3) Synthesis of component A-8: Hyaluronic acid (2g, 340kDa) was dissolved in 100mL 0.01mol / L 2-(N-morpholine)ethanesulfonic acid MES buffer (pH=5.2), stirred until completely dissolved, compound 15 (82mg, 0.2mmol) was weighed and dissolved in 10mL dimethylsulfoxide DMSO, then added to the reaction solution, 4-(4,6-dimethoxytriazin-2-yl)-4-methylmorpholine hydrochloride DMTMM (0.4g, 1.5mmol) was weighed and dissolved in 3mL MES buffer, added to the reaction solution three times (once every hour), and reacted at 35°C for 24 hours. After that, the reaction solution was placed in a dialysis bag (MWCO 7000), dialyzed with deionized water for 2-3 days, and freeze-dried to obtain photosensitive hyaluronic acid derivative A-8 (1.86g). 1 The labeling rate of compound 15 calculated based on the H-NMR spectrum was approximately 3.43%.

[0098] <Example 9> Synthesis of Component A-9 [ka] (1) Synthesis of compound 16: The synthesis is carried out according to the method disclosed in the references Patchornik Abraham.; Amit B.; Woodward RBJ Am. Chem. Soc. 1970, 92, 6333.

[0099] (2) Synthesis of Compound 17: Compound 16 (1 g, 2.5 mmol) and ethylenediamine (1.1 mL) were dissolved in methanol (50 mL) and reacted under reflux overnight. The mixture was then rotary evaporated under reduced pressure, and the crude product was dissolved in methanol and reprecipitated in ethyl acetate. After multiple dissolution-reprecipitation cycles, the product was filtered and dried in vacuum to obtain Compound 17 (0.80 g, 75% yield). 1 H NMR (400mHz, CDCl3): δ=8.02 - 7.23 (m, 5H), 7.71 (s, 1H), 7.22 (s, 1H), 4.96 (s, 2H), 4.13 (t, J=6.1 Hz, 2H), 3.99 (s, 3H), 3.32 (dd, MS (ESI): [M+H] 432.1713. (3) Synthesis of component A-9: Hyaluronic acid (2g, 340kDa) was dissolved in 100mL 0.01mol / L 2-(N-morpholine)ethanesulfonic acid MES buffer (pH=5.2), stirred until completely dissolved, compound 17 (86mg, 0.2mmol) was weighed and dissolved in 10mL dimethylsulfoxide DMSO, then added to the reaction solution, 4-(4,6-dimethoxytriazin-2-yl)-4-methylmorpholine hydrochloride DMTMM (0.4g, 1.5mmol) was weighed and dissolved in 3mL MES buffer, added to the reaction solution three times (once every hour), and reacted at 35°C for 24 hours. After that, the reaction solution was placed in a dialysis bag (MWCO 7000), dialyzed with deionized water for 2-3 days, and freeze-dried to obtain photosensitive hyaluronic acid derivative A-9 (1.82g). 1 The labeling rate of compound 17 calculated based on the H-NMR spectrum was approximately 3.24%.

[0100] <Example 10> Synthesis of Component A-10 [ka] (1) Synthesis of compound 18: The synthesis is carried out according to the method disclosed in the references Patchornik Abraham.; Amit B.; Woodward RBJ Am. Chem. Soc. 1970, 92, 6333.

[0101] (2) Synthesis of Compound 19: Compound 18 (1 g, 2.7 mmol) and ethylenediamine (1.1 mL) were dissolved in methanol (50 mL) and reacted under reflux overnight. The mixture was then rotary evaporated under reduced pressure, and the crude product was dissolved in methanol and reprecipitated in ethyl acetate. After multiple dissolution-reprecipitation cycles, the product was filtered and dried in vacuum to obtain Compound 19 (0.76 g, 71% yield). 1 H NMR (400mHz, CDCl3): δ=7.71 (s, 1H), 7.22 (s, 1H), 4.96 (s, 2H), 4.25 (q, J=6.5 Hz, 2H), 4.13 (t, J=6.1 Hz, 2H), 3.99 (s, 3H), 3.32 (dd, J=11.6, 5.7 Hz, 2H),2.82 (t, J=5.9 Hz, 2H), 2.44 (t, J=7.2 Hz, 2H), 2.26 - 2.17 (m, 2H), 1.32 (t, J=6.5 Hz, 3H). MS (ESI): [M+H] 400.1742. (3) Synthesis of component A-10: Hyaluronic acid (2g, 340kDa) was dissolved in 100mL 0.01mol / L 2-(N-morpholine)ethanesulfonic acid MES buffer (pH=5.2), stirred until completely dissolved, compound 19 (80mg, 0.2mmol) was weighed and dissolved in 10mL dimethylsulfoxide DMSO, then added to the reaction solution, 4-(4,6-dimethoxytriazin-2-yl)-4-methylmorpholine hydrochloride DMTMM (0.4g, 1.5mmol) was weighed and dissolved in 3mL MES buffer, added to the reaction solution three times (once every hour), and reacted at 35°C for 24 hours. After that, the reaction solution was placed in a dialysis bag (MWCO 7000), dialyzed with deionized water for 2-3 days, and freeze-dried to obtain photosensitive hyaluronic acid derivative A-10 (1.88g).1 The labeling rate of compound 19 calculated based on the H-NMR spectrum was approximately 3.01%.

[0102] <Example 11> Synthesis of Component A-11 [ka] (1) Synthesis of compound 20: The synthesis is carried out according to the method disclosed in the references Kalbag, SM; Roeske, RWJ Am. Chem. Soc. 1975, 97, 440.

[0103] (2) Synthesis of Compound 21: Compound 20 (1 g, 2.3 mmol) and ethylenediamine (1.1 mL) were dissolved in methanol (50 mL) and reacted under reflux overnight. The mixture was then rotary evaporated under reduced pressure, and the crude product was dissolved in methanol and reprecipitated in ethyl acetate. After multiple dissolution-reprecipitation cycles, the product was filtered and dried in vacuum to obtain Compound 21 (0.84 g, 79% yield). 1 H NMR (400mHz, CDCl3): δ =7.71 (s, 1H), 7.22 (s, 1H), 4.96 (s, 2H), 4.63 (q, J=6.9 Hz, 1H), 4.13 (t, J=6.1 Hz, 2H), 3.99 (s, 3H), 3.67 MS (ESI): [M+H] 457.1976. (3) Synthesis of component A-11: Hyaluronic acid (2g, 340kDa) was dissolved in 100mL 0.01mol / L 2-(N-morpholine)ethanesulfonic acid MES buffer (pH=5.2), stirred until completely dissolved, compound 21 (91mg, 0.2mmol) was weighed and dissolved in 10mL dimethylsulfoxide DMSO, then added to the reaction solution, 4-(4,6-dimethoxytriazin-2-yl)-4-methylmorpholine hydrochloride DMTMM (0.4g, 1.5mmol) was weighed and dissolved in 3mL MES buffer, added to the reaction solution three times (once every hour), and reacted at 35°C for 24 hours. After that, the reaction solution was placed in a dialysis bag (MWCO 7000), dialyzed with deionized water for 2-3 days, and freeze-dried to obtain photosensitive hyaluronic acid derivative A-11 (1.76g). 1 The labeling rate of compound 21 calculated based on the H-NMR spectrum was approximately 3.15%.

[0104] <Example 12> Synthesis of Component A-12 [ka] (1) Synthesis of compound 22: The synthesis is carried out according to the method disclosed in the references Patchornik Abraham.; Amit B.; Woodward RBJ Am. Chem. Soc. 1970, 92, 6333.

[0105] (2) Synthesis of Compound 23: Compound 22 (1 g, 2.7 mmol) and ethylenediamine (1.1 mL) were dissolved in methanol (50 mL) and reacted under reflux overnight. The mixture was then rotary evaporated under reduced pressure, and the crude product was dissolved in methanol and reprecipitated in ethyl acetate. After multiple dissolution-reprecipitation cycles, the product was filtered and dried in vacuum to obtain Compound 23 (0.76 g, 71% yield). 1H NMR (400mHz, CDCl3): δ=7.71 (s, 1H), 7.22 (s, 1H), 4.96 (s, 2H), 4.25 (q, J=6.5 Hz, 2H), 4.13 (t, J=6.1 Hz, 2H), 3.99 (s, 3H), 3.32 (dd, J=11.6, 5.7 Hz, 2H), 2.82 (t, J=5.9 Hz, 2H), 2.44 (t, J=7.2 Hz, 2H), 2.26 - 2.17 (m, 2H), 1.32 (t, J=6.5 Hz, 3H). MS (ESI): [M+H] 416.1422. (3) Synthesis of component A-12: Hyaluronic acid (2g, 340kDa) was dissolved in 100mL 0.01mol / L 2-(N-morpholine)ethanesulfonic acid MES buffer (pH=5.2), stirred until completely dissolved, compound 23 (80mg, 0.2mmol) was weighed and dissolved in 10mL dimethylsulfoxide DMSO, then added to the reaction solution, 4-(4,6-dimethoxytriazin-2-yl)-4-methylmorpholine hydrochloride DMTMM (0.4g, 1.5mmol) was weighed and dissolved in 3mL MES buffer, added to the reaction solution three times (once every hour), and reacted at 35°C for 24 hours. After that, the reaction solution was placed in a dialysis bag (MWCO 7000), dialyzed with deionized water for 2-3 days, and freeze-dried to obtain photosensitive hyaluronic acid derivative A-12 (1.88g). 1 The labeling rate of compound 23 calculated based on the H-NMR spectrum was approximately 3.01%.

[0106] <Example 13> Synthesis of Component A-13 [ka] (1) Synthesis of Compound 24: Compound 24 is prepared according to the method disclosed in Engels, J.; Schlaeger, EJJ Med. Chem. 1977, 20, 907. 1H NMR (400mHz, CDCl3): δ=7.71 (s, 1H), 7.22 (s, 1H), 4.96 (s, 2H), 4.25 (q, J=6.5 Hz, 2H), 4.13 (t, J=6.1 Hz, 2H), 3.99 (s, 3H), 3.32 (dd, J=11.6, 5.7 Hz, 2H), 2.82 (t, J=5.9 Hz, 2H), 2.44 (t, J=7.2 Hz, 2H), 2.26 - 2.17 (m, 2H), 1.32 (t, J=6.5 Hz, 3H). MS (ESI): [M+H] 435.1432. (2) Synthesis of component A-13: Hyaluronic acid (2g, 340kDa) was dissolved in 100mL 0.01mol / L 2-(N-morpholine)ethanesulfonic acid MES buffer solution (pH=5.2), stirred until completely dissolved, compound 24 (87mg, 0.2mmol) was weighed and dissolved in 10mL dimethylsulfoxide DMSO, then added to the reaction solution, 4-(4,6-dimethoxytriazin-2-yl)-4-methylmorpholine hydrochloride DMTMM (0.4g, 1.5mmol) was weighed and dissolved in 3mL MES buffer solution, added to the reaction solution three times (once every hour), and reacted at 35°C for 24 hours. After that, the reaction solution was placed in a dialysis bag (MWCO 7000), dialyzed with deionized water for 2-3 days, and freeze-dried to obtain photosensitive hyaluronic acid derivative A-13 (1.73g). 1 The labeling rate of compound 24 calculated based on the H-NMR spectrum was approximately 3.08%.

[0107] <Example 21> Synthesis of Component A-21 [ka] (1) Synthesis of Compound 32: The compound is synthesized according to the method disclosed in the references Emmanuel Riguet.; Christian G. Bochet. Org. Lett. 2007, 26, 5453.

[0108] (2) Synthesis of Compound 33: Compound 32 (1 g, 3.4 mmol) and ethylenediamine (1.1 mL) were dissolved in methanol (50 mL) and reacted under reflux overnight. The mixture was then rotary evaporated under reduced pressure, and the crude product was dissolved in methanol and reprecipitated in ethyl acetate. After multiple dissolution-reprecipitation cycles, the product was filtered and dried in vacuum to obtain Compound 33 (0.85 g, 78% yield). 1 H NMR (400mHz, CDCl3): δ=8.05 (d, J=9.54 Hz, 1H), 7.24 (d, J=2.72 Hz, 1H), 6.92 (dd, J=9.54, 2.72 Hz, 1H), 4.85 (s, 2H), 3.56 - 3.68 (m, MS (ESI): [M+H] 346.1454. (3) Synthesis of component A-21: Hyaluronic acid (2g, 340kDa) was dissolved in 100mL 0.01mol / L 2-(N-morpholine)ethanesulfonic acid MES buffer (pH=5.2), stirred until completely dissolved, compound 33 (65mg, 0.2mmol) was weighed and dissolved in 10mL dimethylsulfoxide DMSO, then added to the reaction solution, 4-(4,6-dimethoxytriazin-2-yl)-4-methylmorpholine hydrochloride DMTMM (0.4g, 1.5mmol) was weighed and dissolved in 3mL MES buffer, added to the reaction solution three times (once every hour), and reacted at 35°C for 24 hours. After that, the reaction solution was placed in a dialysis bag (MWCO 7000), dialyzed with deionized water for 2-3 days, and freeze-dried to obtain photosensitive hyaluronic acid derivative A-21 (1.76g). 1 The labeling rate of compound 33 calculated based on the H-NMR spectrum was approximately 2.84%.

[0109] <Example 22> Synthesis of Component A-22 [ka] (1) Synthesis of compound 34: The synthesis is carried out according to the method disclosed in the references Isabelle Aujard.; Chouaha Benbrahim.; Ludovic Jullien. Chem. Eur. J. 2006, 12, 6865.

[0110] (2) Synthesis of Compound 35: Compound 34 (1 g, 3.2 mmol) and ethylenediamine (1.1 mL) were dissolved in methanol (50 mL) and reacted under reflux overnight. The mixture was then rotary evaporated under reduced pressure, and the crude product was dissolved in methanol and reprecipitated in ethyl acetate. After multiple dissolution-reprecipitation cycles, the product was filtered and dried in vacuum to obtain Compound 35 (0.96 g, 88% yield). 1 H NMR (400mHz, CDCl3): δ=8.05 (d, J=9.54 Hz, 1H), 7.28 (d, J=8.00 Hz, 2H), 7.24 (d, J=2.72 Hz, 1H), 6.92 (dd, J=9.54, 2.72 Hz, 1H), 6.78 (d, 8.00 Hz, 2H), 4.96 (s, 2H), 4.83 (s, 2H), 3.32 (t, J=5.9 Hz, 2H), 2.82 (t, J=5.9 Hz, 2H).MS (ESI): [M+H] 346.1454. (3) Synthesis of component A-22: Hyaluronic acid (2g, 340kDa) was dissolved in 100mL 0.01mol / L 2-(N-morpholine)ethanesulfonic acid MES buffer (pH=5.2), stirred until completely dissolved, compound 35 (69mg, 0.2mmol) was weighed and dissolved in 10mL dimethylsulfoxide DMSO, then added to the reaction solution, 4-(4,6-dimethoxytriazin-2-yl)-4-methylmorpholine hydrochloride DMTMM (0.4g, 1.5mmol) was weighed and dissolved in 3mL MES buffer, added to the reaction solution three times (once every hour), and reacted at 35°C for 24 hours. After that, the reaction solution was placed in a dialysis bag (MWCO 7000), dialyzed with deionized water for 2-3 days, and freeze-dried to obtain photosensitive hyaluronic acid derivative A-22 (1.83g). 1The labeling rate of compound 35 calculated based on the H-NMR spectrum was approximately 3.12%.

[0111] <Example 25> Synthesis of Component A-25 [ka] (1) Synthesis of compound 40: The compound is synthesized according to the method disclosed in the references Emmanuel Riguet.; Christian G. Bochet. Org. Lett. 2007, 26, 5453.

[0112] (2) Synthesis of Compound 41: Compound 40 (1 g, 3.6 mmol) and ethylenediamine (1.1 mL) were dissolved in methanol (50 mL) and reacted under reflux overnight. The mixture was then rotary evaporated under reduced pressure, and the crude product was dissolved in methanol and reprecipitated in ethyl acetate. After multiple dissolution-reprecipitation cycles, the product was filtered and dried in vacuum to obtain Compound 41 (0.93 g, 85% yield). 1 H NMR (400mHz, CDCl3): δ=7.71 (s, 1H), 7.22 (s, 1H), 4.96 (s, 2H),4.24 (s, 2H), 3.32 (t, J=5.9 Hz, 2H), 3.27 - 3.21 (m,2H), 2.82 (t, MS (ESI): [M+H] 309.1522. (3) Synthesis of component A-25: Hyaluronic acid (2g, 340kDa) was dissolved in 100mL 0.01mol / L 2-(N-morpholine)ethanesulfonic acid MES buffer (pH=5.2), stirred until completely dissolved, compound 41 (62mg, 0.2mmol) was weighed and dissolved in 10mL dimethylsulfoxide DMSO, then added to the reaction solution, 4-(4,6-dimethoxytriazin-2-yl)-4-methylmorpholine hydrochloride DMTMM (0.4g, 1.5mmol) was weighed and dissolved in 3mL MES buffer, added to the reaction solution three times (once every hour), and reacted at 35°C for 24 hours. After that, the reaction solution was placed in a dialysis bag (MWCO 7000), dialyzed with deionized water for 2-3 days, and freeze-dried to obtain photosensitive hyaluronic acid derivative A-25 (1.82g). 1 The labeling rate of compound 41 calculated based on the H-NMR spectrum was approximately 3.12%.

[0113] <Example 26> Synthesis of Component A-26 [ka] (1) Synthesis of Compound 42: The synthesis is carried out according to the method disclosed in the references Singh, AK; Khade, PK Tetrahedron. 2005, 61, 10007.

[0114] (2) Synthesis of Compound 43: Compound 42 (1 g, 3.4 mmol) and ethylenediamine (1.1 mL) were dissolved in methanol (50 mL) and reacted under reflux overnight. The mixture was then rotary evaporated under reduced pressure, and the crude product was dissolved in methanol and reprecipitated in ethyl acetate. After multiple dissolution-reprecipitation cycles, the product was filtered and dried in vacuum to obtain Compound 43 (0.90 g, 82% yield). 1H NMR (400mHz, CDCl3): δ=8.31 ​​- 7.12 (m, 5H), 4.96 (s, 2H),4.83 (s, 2H), 3.32 (t, J=5.9 Hz, 2H), 2.82 (t, J=5.9 Hz, 2H). MS (ESI): [M+H] 320.1254. (3) Synthesis of component A-26: Hyaluronic acid (2g, 340kDa) was dissolved in 100mL 0.01mol / L 2-(N-morpholine)ethanesulfonic acid MES buffer (pH=5.2), stirred until completely dissolved, compound 43 (64mg, 0.2mmol) was weighed and dissolved in 10mL dimethylsulfoxide DMSO, then added to the reaction solution, 4-(4,6-dimethoxytriazin-2-yl)-4-methylmorpholine hydrochloride DMTMM (0.4g, 1.5mmol) was weighed and dissolved in 3mL MES buffer, added to the reaction solution three times (once every hour), and reacted at 35°C for 24 hours. After that, the reaction solution was placed in a dialysis bag (MWCO 7000), dialyzed with deionized water for 2-3 days, and freeze-dried to obtain photosensitive hyaluronic acid derivative A-26 (1.87g). 1 The labeling rate of compound 43 calculated based on the H-NMR spectrum was approximately 3.21%.

[0115] <Example 28> Synthesis of Component A-28 [ka] (1) Synthesis of compound 46: The synthesis is carried out according to the method disclosed in the references Grazyna Groszek.; Agnieszka Nowak-Krol.; Barbara Filipek. Eur. J. Med. Chem. 2009, 44, 5103.

[0116] (2) Synthesis of Compound 47: Compound 46 (1 g, 3.3 mmol) and ethylenediamine (1.1 mL) were dissolved in methanol (50 mL) and reacted under reflux overnight. The mixture was then rotary evaporated under reduced pressure, and the crude product was dissolved in methanol and reprecipitated in ethyl acetate. After multiple dissolution-reprecipitation cycles, the product was filtered and dried in vacuum to obtain Compound 47 (0.97 g, 89% yield). 1 H NMR (400mHz, CDCl3): δ=8.04 (s, 1H), 7.42 (s, 1H), 4.96 (s, 2H), 4.13 (t, J=6.1 Hz, 2H), 3.99 (s, 3H), 3.32 (dd, J=11.6, 5.7 Hz, 2H), 2.82 (t, J=5.9 Hz, 2H), 2.44 (t, J=7.2 Hz, 2H), 2.26 - 2.17 (m, 2H). MS (ESI): [M+H] 328.1507. (3) Synthesis of component A-28: Hyaluronic acid (2g, 340kDa) was dissolved in 100mL 0.01mol / L 2-(N-morpholine)ethanesulfonic acid MES buffer (pH=5.2), stirred until completely dissolved, weighed out 10mL of compound 47 (65mg, 0.2mmol) and dissolved in dimethylsulfoxide DMSO, then added to the reaction solution, weighed out 4-(4,6-dimethoxytriazin-2-yl)-4-methylmorpholine hydrochloride DMTMM (0.4g, 1.5mmol) and dissolved in 3mL MES buffer, added to the reaction solution three times (once every hour), and reacted at 35°C for 24 hours. After that, the reaction solution was placed in a dialysis bag (MWCO 7000), dialyzed with deionized water for 2-3 days, and freeze-dried to obtain photosensitive hyaluronic acid derivative A-28 (1.85g). 1 The labeling rate of compound 47 calculated based on the H-NMR spectrum was approximately 3.43%.

[0117] <Example 29> Synthesis of Component A-29 [ka] (1) Synthesis of compound 48: Synthesis is performed according to the method disclosed in the references Thomas F. Greene.; Shu Wang.; Mary J. Meegan. J. Med. Chem. 2016, 59, 90.

[0118] (2) Synthesis of Compound 49: Compound 48 (1 g, 3.3 mmol) and ethylenediamine (1.1 mL) were dissolved in methanol (50 mL) and reacted under reflux overnight. The mixture was then rotary evaporated under reduced pressure, and the crude product was dissolved in methanol and reprecipitated in ethyl acetate. After multiple dissolution-reprecipitation cycles, the product was filtered and dried in vacuum to obtain Compound 49 (0.95 g, 87% yield). 1 H NMR (400mHz, CDCl3): δ=7.95 (s, 1H), 7.12 (s, 1H), 4.96 (s, 2H), 4.13 (t, J=6.1 Hz, 2H), 3.99 (s, 3H), 3.32 (dd, J=11.6, 5.7 Hz, 2H), 2.82 (t, J=5.9 Hz, 2H), 2.44 (t, J=7.2 Hz, 2H), 2.26 - 2.17 (m, 2H). MS (ESI): [M+H] 328.1507. (3) Synthesis of component A-29: Hyaluronic acid (2g, 340kDa) was dissolved in 100mL 0.01mol / L 2-(N-morpholine)ethanesulfonic acid MES buffer (pH=5.2), stirred until completely dissolved, compound 49 (65mg, 0.2mmol) was weighed and dissolved in 10mL dimethylsulfoxide DMSO, then added to the reaction solution, 4-(4,6-dimethoxytriazin-2-yl)-4-methylmorpholine hydrochloride DMTMM (0.4g, 1.5mmol) was weighed and dissolved in 3mL MES buffer, added to the reaction solution three times (once every hour), and reacted at 35°C for 24 hours. After that, the reaction solution was placed in a dialysis bag (MWCO 7000), dialyzed with deionized water for 2-3 days, and freeze-dried to obtain photosensitive hyaluronic acid derivative A-29 (1.86g). 1 The labeling rate of compound 49 calculated based on the H-NMR spectrum was approximately 3.52%.

[0119] <Example 30> Synthesis of Component A-30 [ka] (1) Synthesis of compound 50: The synthesis is carried out according to the method disclosed in the references Yu-Shan.; Mohane Selvaraj Coumar.; Hsing-Pang Hsieh. J. Med. Chem. 2009, 52, 4941.

[0120] (2) Synthesis of Compound 51: Compound 50 (1 g, 3.3 mmol) and ethylenediamine (1.1 mL) were dissolved in methanol (50 mL) and reacted under reflux overnight. The mixture was then rotary evaporated under reduced pressure, and the crude product was dissolved in methanol and reprecipitated in ethyl acetate. After multiple dissolution-reprecipitation cycles, the product was filtered and dried in vacuum to obtain Compound 51 (0.89 g, 81% yield). 1 H NMR (400mHz, CDCl3): δ=7.64 (s, 1H), 7.02 (s, 1H), 4.96 (s, 2H), 4.13 (t, J=6.1 Hz, 2H), 3.99 (s, 3H), 3.32 (dd, J=11.6, 5.7 Hz, 2H), 2.82 (t, J=5.9 Hz, 2H), 2.44 (t, J=7.2 Hz, 2H), 2.26 - 2.17 (m, 2H). MS (ESI): [M+H] 328.1507. (3) Synthesis of component A-30: Hyaluronic acid (2g, 340kDa) was dissolved in 100mL 0.01mol / L 2-(N-morpholine)ethanesulfonic acid MES buffer (pH=5.2), stirred until completely dissolved, compound 51 (65mg, 0.2mmol) was weighed and dissolved in 10mL dimethylsulfoxide DMSO, then added to the reaction solution, 4-(4,6-dimethoxytriazin-2-yl)-4-methylmorpholine hydrochloride DMTMM (0.4g, 1.5mmol) was weighed and dissolved in 3mL MES buffer, added to the reaction solution three times (once every hour), and reacted at 35°C for 24 hours. After that, the reaction solution was placed in a dialysis bag (MWCO 7000), dialyzed with deionized water for 2-3 days, and freeze-dried to obtain photosensitive hyaluronic acid derivative A-30 (1.82g). 1 The labeling rate of compound 51 calculated based on the H-NMR spectrum was approximately 3.39%.

[0121] <Example 31> Synthesis of Component A-31 [ka] (1) Synthesis of compound 52: The synthesis is carried out according to the method disclosed in the references Sarit S. Agasti.; Apiwat Chompoosor.; Vincent M. Rotello. J. Am. Chem. Soc. 2009, 131, 5728.

[0122] (2) Synthesis of Compound 53: Compound 52 (1 g, 2.9 mmol) and ethylenediamine (1.1 mL) were dissolved in methanol (50 mL) and reacted under reflux overnight. The mixture was then rotary evaporated under reduced pressure, and the crude product was dissolved in methanol and reprecipitated in ethyl acetate. After multiple dissolution-reprecipitation cycles, the product was filtered and dried in vacuum to obtain Compound 53 (0.91 g, 84% yield). 1H NMR (400mHz, CDCl3): δ=7.91 (s, 1H), 4.96 (s, 2H), 4.13 (t, J=6.1 Hz, 2H), 3.99 (s, 3H), 3.32 (dd, J=11.6, 5.7 Hz, 2H), 2.82 (t, J=5.9 Hz, 2H), 2.44 (t, J=7.2 Hz, 2H), 2.26 - 2.17 (m, 2H). MS (ESI): [M+H] 373.1373. (3) Synthesis of component A-31: Hyaluronic acid (2g, 340kDa) was dissolved in 100mL 0.01mol / L 2-(N-morpholine)ethanesulfonic acid MES buffer (pH=5.2), stirred until completely dissolved, compound 53 (75mg, 0.2mmol) was weighed and dissolved in 10mL dimethylsulfoxide DMSO, then added to the reaction solution, 4-(4,6-dimethoxytriazin-2-yl)-4-methylmorpholine hydrochloride DMTMM (0.4g, 1.5mmol) was weighed and dissolved in 3mL MES buffer, added to the reaction solution three times (once every hour), and reacted at 35°C for 24 hours. After that, the reaction solution was placed in a dialysis bag (MWCO 7000), dialyzed with deionized water for 2-3 days, and freeze-dried to obtain photosensitive hyaluronic acid derivative A-31 (1.87g). 1 The labeling rate of compound 53 calculated based on the H-NMR spectrum was approximately 3.45%.

[0123] <Example 33> Synthesis of Component A-33 [ka] Synthesis of component A-33: Hyaluronic acid (2g, 340kDa) was dissolved in 100mL 0.01mol / L 2-(N-morpholine)ethanesulfonic acid MES buffer (pH=5.2), stirred until completely dissolved, NB mixture (compound 1 / compound 55,60mg, weight ratio 1:1) was weighed and dissolved in 10mL dimethylsulfoxide DMSO, then added to the reaction solution, 4-(4,6-dimethoxytriazin-2-yl)-4-methylmorpholine hydrochloride DMTMM (0.4g, 1.5mmol) was weighed and dissolved in 3mL MES buffer, added to the reaction solution three times (once every hour), and reacted at 35°C for 24 hours. After that, the reaction solution was placed in a dialysis bag (MWCO 7000), dialyzed with deionized water for 2-3 days, and freeze-dried to obtain photosensitive hyaluronic acid derivative A-33 (1.87g). 1 The labeling rate of the NB mixture (compound 1 / compound 55) calculated based on the H-NMR spectrum was approximately 3.52%.

[0124] <Example 34> Synthesis of Component A-34 [ka] (1) Synthesis of compound 56: Synthesis is performed according to the method disclosed in the references Pauloehrl, T.; Delaittre, G.; Bruns, M.; Meiβler, M.; Bοrner, HG; Bastmeyer, M.; Barner-Kowollik, C. Angew. Chem. Int. Ed. 2012, 51, 9181.

[0125] (2) Synthesis of Compound 57: Compound 56 (1 g, 3.3 mmol) and ethylenediamine (1.1 mL) were dissolved in methanol (50 mL) and reacted under reflux overnight. The mixture was then rotary evaporated under reduced pressure, and the crude product was dissolved in methanol and reprecipitated in ethyl acetate. After multiple dissolution-reprecipitation cycles, the product was filtered and dried in vacuum to obtain Compound 57 (0.93 g, 85% yield). 1H NMR (400mHz, CDCl3): δ=7.71 (s, 1H), 7.22 (s, 1H), 4.96 (s, 2H), 3.99 (s, 3H), 3.32 (t, J=5.7 Hz, 2H), 2.82 (t, J=5.9 Hz, 2H), 2.55 (t, J=6.1 Hz, 2H),2.44 (t, J=7.2 Hz, 2H), 2.26 - 2.17 (m, 2H). MS (ESI): [M+H] 326.1721. (3) Synthesis of component A-34: Hyaluronic acid (2g, 340kDa) was dissolved in 100mL 0.01mol / L 2-(N-morpholine)ethanesulfonic acid MES buffer (pH=5.2), stirred until completely dissolved, compound 57 (65mg, 0.2mmol) was weighed and dissolved in 10mL dimethylsulfoxide DMSO, then added to the reaction solution, 4-(4,6-dimethoxytriazin-2-yl)-4-methylmorpholine hydrochloride DMTMM (0.4g, 1.5mmol) was weighed and dissolved in 3mL MES buffer, added to the reaction solution three times (once every hour), and reacted at 35°C for 24 hours. After that, the reaction solution was placed in a dialysis bag (MWCO 7000), dialyzed with deionized water for 2-3 days, and freeze-dried to obtain photosensitive hyaluronic acid derivative A-34 (1.82g). 1 The labeling rate of compound 57 calculated based on the H-NMR spectrum was approximately 3.21%.

[0126] <Example 35> Synthesis of Component A-35 [ka] (1) Synthesis of compound 58: Synthesis is performed according to the method disclosed in the references Pauloehrl, T.; Delaittre, G.; Bruns, M.; Meiβler, M.; Bοrner, HG; Bastmeyer, M.; Barner-Kowollik, C. Angew. Chem. Int. Ed. 2012, 51, 9181.

[0127] (2) Synthesis of Compound 59: Compound 58 (1 g, 3.3 mmol) and ethylenediamine (1.1 mL) were dissolved in methanol (50 mL) and reacted under reflux overnight. The mixture was then rotary evaporated under reduced pressure, and the crude product was dissolved in methanol and reprecipitated in ethyl acetate. After multiple dissolution-reprecipitation cycles, the product was filtered and dried in vacuum to obtain Compound 59 (0.82 g, 75% yield). 1 H NMR (400mHz, CDCl3): δ=7.71 (s, 1H), 7.22 (s, 1H), 4.96 (s, 2H), 4.03 (t, J=6.1 Hz, 2H), 3.99 (s, 3H), 3.32 (dd, J=11.6, 5.7 Hz, 2H), 2.82 (t, J=5.9 Hz, 2H), 2.44 (t, J=7.2 Hz, 2H), 2.26 - 2.17 (m, 2H). MS (ESI): [M+H] 360.1213. (3) Synthesis of component A-35: Hyaluronic acid (2g, 340kDa) was dissolved in 100mL 0.01mol / L 2-(N-morpholine)ethanesulfonic acid MES buffer (pH=5.2), stirred until completely dissolved, compound 59 (65mg, 0.2mmol) was weighed and dissolved in 10mL dimethylsulfoxide DMSO, then added to the reaction solution, 4-(4,6-dimethoxytriazin-2-yl)-4-methylmorpholine hydrochloride DMTMM (0.4g, 1.5mmol) was weighed and dissolved in 3mL MES buffer, added to the reaction solution three times (once every hour), and reacted at 35°C for 24 hours. After that, the reaction solution was placed in a dialysis bag (MWCO 7000), dialyzed with deionized water for 2-3 days, and freeze-dried to obtain photosensitive hyaluronic acid derivative A-35 (1.87g). 1 The labeling rate of compound 59 was calculated to be about 2.76% based on the H-NMR spectrum.

[0128] <Example 36> Synthesis of Component A-36 [ka] (1) Synthesis of compound 60: Synthesis is performed according to the method disclosed in the references Pauloehrl, T.; Delaittre, G.; Bruns, M.; Meiβler, M.; Bοrner, HG; Bastmeyer, M.; Barner-Kowollik, C. Angew. Chem. Int. Ed. 2012, 51, 9181.

[0129] (2) Synthesis of Compound 61: Compound 60 (1 g, 3.3 mmol) and ethylenediamine (1.1 mL) were dissolved in methanol (50 mL) and reacted under reflux overnight. The mixture was then rotary evaporated under reduced pressure, and the crude product was dissolved in methanol and reprecipitated in ethyl acetate. After multiple dissolution-reprecipitation cycles, the product was filtered and dried in vacuum to obtain Compound 61 (0.80 g, 73% yield). 1 H NMR (400mHz, CDCl3): δ=7.71 (s, 1H), 7.22 (s, 1H), 4.96 (s, 2H), 3.99 (s, 3H),3.45 (t, J=6.1 Hz, 2H), 3.32 (dd, J=11.6, 5.7 Hz, 2H), 2.82 (t, J=5.9 Hz, 2H), 2.44 (t, J=7.2 Hz, 2H), 2.26 - 2.17 (m, 2H). MS (ESI): [M+H] 327.1625. (3) Synthesis of component A-36: Hyaluronic acid (2g, 340kDa) was dissolved in 100mL 0.01mol / L 2-(N-morpholine)ethanesulfonic acid MES buffer (pH=5.2), stirred until completely dissolved, compound 61 (65mg, 0.2mmol) was weighed and dissolved in 10mL dimethylsulfoxide DMSO, then added to the reaction solution, 4-(4,6-dimethoxytriazin-2-yl)-4-methylmorpholine hydrochloride DMTMM (0.4g, 1.5mmol) was weighed and dissolved in 3mL MES buffer, added to the reaction solution three times (once every hour), and reacted at 35°C for 24 hours. After that, the reaction solution was placed in a dialysis bag (MWCO 7000), dialyzed with deionized water for 2-3 days, and freeze-dried to obtain photosensitive hyaluronic acid derivative A-36 (1.76g). 1 The labeling rate of compound 61 calculated based on the H-NMR spectrum was approximately 3.21%.

[0130] <Example 37> Synthesis of Component A-37 [ka] Synthesis of component A-37: Carboxymethyl cellulose (2g, 90kDa) was dissolved in 100mL 0.01mol / L 2-(N-morpholine)ethanesulfonic acid MES buffer (pH=5.2), stirred until completely dissolved, compound 1 (65mg, 0.2mmol) was weighed and dissolved in 10mL dimethylsulfoxide DMSO, and then added to the reaction solution, 4-(4,6-dimethoxytriazin-2-yl)-4-methylmorpholine hydrochloride DMTMM (0.4g, 1.5mmol) was weighed and dissolved in 3mL MES buffer, and added to the reaction solution three times (once every hour), and reacted at 35°C for 24 hours. Then, the reaction solution was placed in a dialysis bag (MWCO 7000), dialyzed with deionized water for 2-3 days, and freeze-dried to obtain photosensitive carboxymethyl cellulose derivative A-37 (1.89g). 1 The labeling rate of Compound 1 calculated based on the H-NMR spectrum was approximately 2.25%.

[0131] <Example 38> Synthesis of Component A-38 [ka] Synthesis of component A-38: Alginic acid (2 g) was dissolved in 100 mL 0.01 mol / L 2-(N-morpholine)ethanesulfonic acid MES buffer (pH = 5.2), stirred until completely dissolved, compound 1 (65 mg, 0.2 mmol) was weighed and dissolved in 10 mL dimethyl sulfoxide DMSO, and then added to the reaction solution, 4-(4,6-dimethoxytriazin-2-yl)-4-methylmorpholine hydrochloride DMTMM (0.4 g, 1.5 mmol) was weighed and dissolved in 3 mL MES buffer, and added to the reaction solution three times (once every hour), and reacted at 35 ° C. for 24 hours. Thereafter, the reaction solution was placed in a dialysis bag (MWCO 7000), dialyzed with deionized water for 2-3 days, and freeze-dried to obtain photosensitive alginic acid derivative A-38 (1.82 g). 1 The labeling rate of compound 1 calculated based on the H-NMR spectrum was approximately 3.17%.

[0132] <Example 39> Synthesis of Component A-39 [ka] Synthesis of component A-39: Chondroitin sulfate (2g) was dissolved in 100mL 0.01mol / L 2-(N-morpholine)ethanesulfonic acid MES buffer (pH=5.2), stirred until completely dissolved, weighed compound 1 (65mg, 0.2mmol) and dissolved in 10mL dimethylsulfoxide DMSO, then added to the reaction solution, weighed 4-(4,6-dimethoxytriazin-2-yl)-4-methylmorpholine hydrochloride DMTMM (0.4g, 1.5mmol) and dissolved in 3mL MES buffer, added to the reaction solution three times (once every hour), and reacted at 35°C for 24 hours. Then, the reaction solution was placed in a dialysis bag (MWCO 7000), dialyzed with deionized water for 2-3 days, and freeze-dried to obtain photosensitive chondroitin sulfate derivative A-39 (1.73g). 1 The labeling rate of compound 1 calculated based on the H-NMR spectrum was approximately 2.98%.

[0133] <Example 40> Synthesis of Component A-40 [ka] Synthesis of component A-40: Polyglutamic acid PGA (1g) was completely dissolved in 50mL distilled water, and hydroxybenzotriazole (HOBt, 0.3g, 2.3mmol) was added, and then compound 1 (0.5g, 1.6mmol) dissolved in methanol and 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC-HCl, 0.5g, 2.6mmol) were added to the solution, and the mixture was reacted at room temperature for 48 hours, and then the mixture was dialyzed with a dilute hydrochloric acid solution (pH=3.5) containing sodium chloride for one day, and then dialyzed with pure water for one day, and freeze-dried to obtain photosensitive polyglutamic acid derivative A-40 (0.92g). The modification degree of compound 1 calculated based on its 1H-NMR spectrum was about 21.3%.

[0134] <Example 41> Synthesis of Component A-41 [ka] Synthesis of component A-41: 4-arm polyethylene glycol carboxylic acid derivative 4-PEG-COOH (0.5 g, 10 kDa) was completely dissolved in 20 mL anhydrous dimethyl sulfoxide DMSO, and compound 1 (130 mg, 0.4 mmol) was dissolved in 5 mL anhydrous dimethyl sulfoxide DMSO, and then added to the reaction solution, 0.2 mL triethylamine TEA was added, and hexafluorophosphate benzotriazol-1-yl-oxytripyrrolidinyl phosphonium PyBop (210 mg, 0.4 mmol) was added, and the mixture was reacted at room temperature for 24 hours, and then reprecipitated in diethyl ether. The crude product was dissolved in water, then placed in a dialysis bag (MWCO 3500), dialyzed with deionized water for 2-3 days, and freeze-dried to obtain photosensitive polyethylene glycol derivative A-41 (0.45 g). 1 The labeling rate of compound 1 calculated based on the H-NMR spectrum was approximately 98%.

[0135] <Example 42> Synthesis of Component A-42 [ka] (1) Synthesis of compound 62: Synthesis is performed according to the method disclosed in the references Pauloehrl, T.; Delaittre, G.; Bruns, M.; Meiβler, M.; Bοrner, HG; Bastmeyer, M.; Barner-Kowollik, C. Angew. Chem. Int. Ed. 2012, 51, 9181. 1 H NMR (400mHz, CDCl3): δ=7.71 (s, 1H), 7.22 (s, 1H), 4.96 (s, 2H), 4.13 (t, J=6.1 Hz, 2H), 3.99 (s, 3H), 3.90 - 3.80 (m, 1H), 3.79 (t, MS (ESI): [M+H] 372.1627. (2) Synthesis of component A-42: Hyaluronic acid (1 g, 340 kDa) was dissolved in 50 mL of water, and compound 62 (0.2 g, 0.48 mmol), EDC-HCl (0.76 g, 3.96 mmol) and DPTS (0.12 g, 0.48 mmol) were added to the solution in that order, and the mixture was allowed to react at room temperature for 48 hours while stirring. After the reaction was completed, the reaction solution was added to cold ethanol and purified by multiple reprecipitations. The collected precipitate was dried, dissolved in anhydrous DMSO, and p-toluenesulfonic acid was added to remove the dihydropyran protecting group, to obtain photosensitive hyaluronic acid derivative A-42 (0.86 g). 1 The modification degree of compound 62 was calculated to be about 10% based on the H-NMR spectrum.

[0136] <Example 43> Synthesis of Component A-43 [ka] (1) Synthesis of compound 63: Synthesis is performed according to the method disclosed in the references Pauloehrl, T.; Delaittre, G.; Bruns, M.; Meiβler, M.; Bοrner, HG; Bastmeyer, M.; Barner-Kowollik, C. Angew. Chem. Int. Ed. 2012, 51, 9181. 1 H NMR (400mHz, CDCl3): δ=7.71 (s, 1H), 7.22 (s, 1H), 4.96 (s, 2H), 4.13 (t, J=6.1 Hz, 2H), 3.99 (s, 3H), 3.90 - 3.80 (m, 1H), 3.63 - 3.52(m, 1H), 2.44 (t, J=7.2 Hz, 2H), 2.26 - 2.17 (m, 2H), 2.00 - 1.34 (m, 6H). MS (ESI): [M+H] 370.1512. (2) Synthesis of component A-43: 1 g of chitosan was added to 75 mL of isopropanol to prepare a chitosan suspension, and then compound 63 (0.2 g, 0.54 mmol), EDC-HCl (0.76 g, 3.96 mmol) and NHS (0.46 g, 4.0 mmol) were added to the solution in that order, and the mixture was reacted at room temperature for 48 hours while stirring. After the reaction was completed, the mixture was filtered, and the filtrate was dialyzed three times with a mixed solvent of methanol / water, dialyzed twice with methanol, and then freeze-dried to obtain chitosan (0.9 g) labeled with compound 63. The chitosan labeled with compound 63 was dissolved in DMSO, and p-toluenesulfonic acid was added to remove the dihydropyran protecting group to obtain photosensitive chitosan derivative A-43. 1 The modification degree of compound 63 was calculated to be about 12.5% ​​based on the H-NMR spectrum.

[0137] <Example 44> Synthesis of component A-44 [ka] Synthesis of component A-44: Polylysine PLL (1 g) was dissolved in 50 mL of water, and compound 63 (0.2 g, 0.54 mmol), EDC-HCl (0.76 g, 3.96 mmol) and NHS (0.46 g, 4.0 mmol) were added to the solution in that order, and the mixture was reacted at room temperature for 48 hours while stirring. After the reaction was completed, the reaction solution was poured into cold ethanol and purified by multiple reprecipitations. The collected precipitate was dried, dissolved in anhydrous DMSO, and p-toluenesulfonic acid was added to remove the dihydropyran protecting group, to obtain photosensitive polylysine derivative A-44 (0.84 g). 1 The modification degree of compound 63 was calculated to be about 15.6% based on the H-NMR spectrum.

[0138] <Example 45> Synthesis of Component A-45 [ka] Synthesis of component A-45: Gelatin (1 g) was completely dissolved in 50 mL of distilled water, and compound 63 (0.2 g, 0.54 mmol), EDC-HCl (0.76 g, 3.96 mmol) and NHS (0.46 g, 4.0 mmol) were added to the solution in that order, and the mixture was reacted at room temperature for 48 hours while stirring. After the reaction was completed, the reaction solution was poured into cold ethanol and purified by multiple reprecipitations. The collected precipitate was dried, dissolved in anhydrous DMSO, and p-toluenesulfonic acid was added to remove the dihydropyran protecting group, to obtain photosensitive gelatin derivative A-45 (0.83 g). 1 The modification degree of compound 63 was calculated to be about 11.2% based on the H-NMR spectrum.

[0139] <Example 46> Synthesis of Component A-46 [ka] Synthesis of component A-46: Glucan Dextran (1 g) was dissolved in 50 mL of water, and compound 63 (0.23 g, 0.54 mmol), EDC-HCl (0.76 g, 3.96 mmol) and DPTS (0.12 g, 0.48 mmol) were added to the solution in that order, and the mixture was allowed to react at room temperature for 48 hours while stirring. After the reaction was completed, the reaction solution was poured into cold ethanol and purified by multiple reprecipitations. The collected precipitate was dried, dissolved in anhydrous DMSO, and p-toluenesulfonic acid was added to remove the dihydropyran protecting group, to obtain photosensitive glucan derivative A-46 (0.92 g). 1 The modification degree of compound 63 was calculated to be about 18.2% based on the H-NMR spectrum.

[0140] <Example 47> Synthesis of Component A-47 [ka] (1) Synthesis of compound 64: Synthesis is performed according to the method disclosed in the references Pauloehrl, T.; Delaittre, G.; Bruns, M.; Meiβler, M.; Bοrner, HG; Bastmeyer, M.; Barner-Kowollik, C. Angew. Chem. Int. Ed. 2012, 51, 9181. 1 H NMR (400mHz, CDCl3): δ=7.71 (s, 1H), 7.22 (s, 1H), 4.96 (s, 2H), 4.13 (t, J=6.1 Hz, 2H), 3.99 (s, 3H),2.44 (t, J=7.2 Hz, 2H), 2.26 - 2.17 (m, 2H). MS (ESI): [M+H] 286.0943. (2) Synthesis of component A-47: Heparin modified with a mercapto group Hep-SH (1 g) was completely dissolved in 50 mL of distilled water, and hydroxybenzotriazole (HOBt, 0.3 g, 2.3 mmol) was added. Compound 64 (0.5 g, 1.6 mmol) and 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC-HCl, 0.5 g, 2.6 mmol) dissolved in methanol were added to the solution, and the mixture was reacted at room temperature for 48 hours. The mixture was then dialyzed for one day against a dilute hydrochloric acid solution (pH = 3.5) containing sodium chloride, and then further dialyzed for one day against pure water, and freeze-dried to obtain photosensitive heparin derivative A-47 (0.86 g). 1 The modification degree of compound 64 was calculated to be about 10.2% based on the H-NMR spectrum.

[0141] <Example 48> Synthesis of component A-48 [ka] (1) Synthesis of compound 65: Synthesis is performed according to the method disclosed in the references Pauloehrl, T.; Delaittre, G.; Bruns, M.; Meiβler, M.; Bοrner, HG; Bastmeyer, M.; Barner-Kowollik, C. Angew. Chem. Int. Ed. 2012, 51, 9181. 1 H NMR (400mHz, CDCl3): δ=7.71 (s, 1H), 7.22 (s, 1H), 4.96 (s, 2H), 4.13 (t, J=6.1 Hz, 2H), 3.99 (s, 3H), 3.90 - 3.80 (m, 1H), 3.63 - 3.52(m, 1H), 3.04 (t, J=7.2 Hz, 2H), 2.00 - 1.34 (m, 6H). MS (ESI): [M+H] 391.0518. (2) Synthesis of component A-48: 1 g of chitosan was added to 75 mL of isopropanol to prepare a chitosan suspension, and 25 mL of NaOH solution (10 mol / L) was slowly added to the chitosan suspension in five portions and stirred for about 30 minutes. Compound 65 (0.2 g) was then added to the solution and reacted at 60°C for 3 hours. After the reaction was completed, the mixture was filtered, and the filtrate was dialyzed three times with a mixed solvent of methanol / water, dialyzed twice with methanol, and then freeze-dried to obtain chitosan labeled with compound 65 (0.92 g). Chitosan labeled with compound 65 was dissolved in DMSO, and p-toluenesulfonic acid was added to remove the dihydropyran protecting group to obtain photosensitive chitosan derivative A-48 (0.84 g). 1 The modification degree of compound 65 was calculated to be about 12.4% based on the H-NMR spectrum.

[0142] <Example 49> Synthesis of Component A-49 [ka] Synthesis of component A-49: PEG-4OH (1g, 0.05mmol) was dissolved in anhydrous acetonitrile, K2CO3 (55.3mg, 0.4mmol) was added and stirred for 30 minutes, after which compound 65 (0.17g, 0.4mmol) was added and the reaction was continued at room temperature for 24 hours. After the reaction was completed, most of the solvent was removed, reprecipitated in diethyl ether, and washed multiple times, after which the polyethylene glycol labeled with compound 65 was dissolved in DMSO, and p-toluenesulfonic acid was added to remove the dihydropyran protecting group to obtain the photosensitive polyethylene glycol derivative A-49 (0.93g). 1 The degree of modification of compound 65 was calculated to be about 95% based on the H-NMR spectrum.

[0143] <Example 50> Synthesis of Component A-50 [ka] (1) Synthesis of Compound 66: Compound 65 (0.5 g, 1.29 mmol) and ethylene glycol (0.24 g, 3.87 mmol) were dissolved in anhydrous acetonitrile, K2CO3 (0.5 g, 3.87 mmol) was added as a base, and the mixture was allowed to react overnight under reflux. After the reaction was completed, the solvent was removed by rotary evaporation under reduced pressure, and compound 66 (0.34 g, 72%) was obtained by column purification. 1 H NMR (400mHz, CDCl3): δ=7.71 (s, 1H), 7.22 (s, 1H), 4.96 (s, 2H), 4.13 (t, J=6.1 Hz, 2H), 3.99 (s, 3H), 3.90 - 3.80 (m, 1H), 3.79 (t, MS (ESI): [M+H] 372.1627.

[0144] (2) Synthesis of Compound 67: Compound 66 (0.64 g, 1.72 mmol) and triethylamine (0.34 g, 3.44 mmol) were dissolved in dry dichloromethane, and methacryloyl chloride (0.27 g, 2.58 mmol) was slowly added dropwise to the solution under ice bath conditions. After the addition was completed, the mixture was allowed to react overnight at room temperature. After the reaction was completed, the solvent was removed by rotary evaporation under reduced pressure, and compound 67 (0.49 g, 65%) was obtained by column purification. 1 H NMR (400mHz, CDCl3): δ=7.71 (s, 1H), 7.22 (s, 1H), 6.25 (s, 1H), 5.68 (s, 1H), 4.96 (s, 2H), 4.13 (t, J=6.1 Hz, 2H), 3.99 (s, 3H), 3.90 - 3.80 (m, 1H), 3.79 (t, J=6.1 Hz, 2H), 3.70 (t, J=7.2 Hz, 2H), 3.63 - 3.52(m, 1H),3.56 (t, J=7.2 Hz, 2H), 2.00 - 1.34 (m, 6H), 1.87 (s, 3H). MS (ESI): [M+H] 440.1942. (3) Synthesis of component A-50: Compound 67 (0.28 g, 0.63 mmol), comonomer PEG-MA (0.882 g, 2.52 mmol) and initiator azobisisobutyronitrile (11 mg) were weighed and added to a Schreck tube, anhydrous THF was added to dissolve, and the reaction system was reacted for 24 hours under the condition of 75 ° C. After the reaction was completed, the reaction solution was put into cold diethyl ether and purified by multiple reprecipitations. The collected precipitate was dried, dissolved in anhydrous DMSO, and p-toluenesulfonic acid was added to remove the dihydropyran protecting group to obtain photosensitive copolymer derivative A-50 (0.84 g). 1 The content of compound 67 in the copolymer was calculated to be about 15.5% based on the H-NMR spectrum. The molecular weight of the synthetic polymer measured by GPC was about 25 kDa. As a result of calculation based on the blending ratio, n was 12, x was 10, and y was 40.

[0145] <Example 51> Synthesis of Component A-51 [ka] (1) Synthesis of compound 68: The compound is synthesized according to the method disclosed in the reference Kunihiko Morihiro.; Tetsuya Kodama.; Shohei Mori.; Satoshi Obika. Org. Biomol. Chem. 2014, 12, 2468. 1 H NMR (400mHz, CDCl3): δ=7.71 (s, 1H), 7.22 (s, 1H), 4.03 (s, 2H), 4.13 (t, J=6.1 Hz, 2H), 3.99 (s, 3H), 3.32 (dd, J=11.6, 5.7 Hz, 2H), 2.82 (t, J=5.9 Hz, 2H), 2.44 (t, J=7.2 Hz, 2H), 2.26 - 2.17 (m, 2H). MS (ESI): [M+H] 344.1207. (2) Synthesis of component A-51: Hyaluronic acid (2g, 340kDa) was dissolved in 100mL 0.01mol / L 2-(N-morpholine)ethanesulfonic acid MES buffer (pH=5.2), stirred until completely dissolved, compound 68 (69mg, 0.2mmol) was weighed and dissolved in 10mL dimethylsulfoxide DMSO, then added to the reaction solution, 4-(4,6-dimethoxytriazin-2-yl)-4-methylmorpholine hydrochloride DMTMM (0.4g, 1.5mmol) was weighed and dissolved in 3mL MES buffer, added to the reaction solution three times (once every hour), and reacted at 35°C for 24 hours. After that, the reaction solution was placed in a dialysis bag (MWCO 7000), dialyzed with deionized water for 2-3 days, and freeze-dried to obtain photosensitive hyaluronic acid derivative A-51 (1.85g). 1 The labeling rate of compound 68 was calculated to be about 3.34% based on the H-NMR spectrum.

[0146] <Example 52> Synthesis of Component A-52 [ka] (1) Synthesis of compound 69: The synthesis is carried out according to the method disclosed in the reference Yunlong Yang; Jieyuan Zhang; Zhenzhen Liu; Qiuning Lin; Xiaolin Liu; Chunyan Bao; Yang Wang; Linyong Zhu. Adv. Mater. 2016, 28, 2724.

[0147] (2) Synthesis of compound 70: Compound 69 (1 g, 3.0 mmol) was dissolved in 50 mL of tetrahydrofuran, and carbon tetrabromide CBr4 (2 g, 6.0 mmol) and triphenylphosphine PPh3 (1.6 g, 6.0 mmol) were added thereto. The mixture was reacted for 2 hours at room temperature under argon protection with stirring. After the reaction was completed, 5 mL of water was added to terminate the reaction. The solvent was removed by rotary evaporation, and the mixture was extracted with ethyl acetate and separated by column chromatography (PE:DCM=4:1) to obtain compound 70 (1.0 g, yield 84%). 1 H NMR (400mHz, CDCl3): δ=7.71 (s, 1H), 7.22 (s, 1H), 4.56 (s, 2H), 4.13 (t, J=6.1 Hz, 2H), 3.99 (s, 3H), 3.32 (dd, J=11.6, 5.7 Hz, 2H), 2.82 (t, J=5.9 Hz, 2H), 2.44 (t, J=7.2 Hz, 2H), 2.26 - 2.17 (m, 2H). MS (ESI): [M+H] 390.0623.

[0148] (3) Synthesis of Compound 71: Compound 70 (0.5 g, 1.3 mmol) was dissolved in 50 mL of acetone, and L-cysteine ​​methyl ester hydrochloride (0.45 g, 2.6 mmol) and sodium hydroxide (0.2 g, 5.2 mmol) were added. The mixture was reacted for 2 hours at room temperature under argon protection with stirring. After the reaction was completed, 4 M HCl was added to adjust the pH to 7. The solvent was removed by rotary evaporation, and the mixture was extracted with ethyl acetate and separated by column chromatography (PE:DCM=4:1) to obtain Compound 71 (0.7 g, 88% yield). 1H NMR (400mHz, CDCl3): δ=7.71 (s, 1H), 7.22 (s, 1H), 4.76 (s, 2H), 4.42 (m, 1H), 4.13 (t, J=6.1 Hz, 2H), 3.99 (s, 3H), 3.95 (s, 3H), 3.43 (d, J=5.6, 2H), 3.32 (dd, J=11.6, 5.7 Hz, 2H), 2.82 (t, J=5.9 Hz, 2H), 2.44 (t, J=7.2 Hz, 2H), 2.26 - 2.17 (m, 2H), 1.42 (s, 9H). MS (ESI): [M+H] 545.2219. (4) Synthesis of component A-52: Hyaluronic acid (2g, 340kDa) was dissolved in 100mL 0.01mol / L 2-(N-morpholine)ethanesulfonic acid MES buffer (pH=5.2), stirred until completely dissolved, compound 71 (109mg, 0.2mmol) was weighed and dissolved in 10mL dimethylsulfoxide DMSO, then added to the reaction solution, 4-(4,6-dimethoxytriazin-2-yl)-4-methylmorpholine hydrochloride DMTMM (0.4g, 1.5mmol) was weighed and dissolved in 3mL MES buffer, added to the reaction solution three times (once every hour), and reacted at 35°C for 24 hours. After that, the reaction solution was placed in a dialysis bag (MWCO 7000), dialyzed with deionized water for 2-3 days, and freeze-dried to obtain photosensitive hyaluronic acid derivative A-52 (1.92g). 1 The labeling rate of compound 71 calculated based on the H-NMR spectrum was approximately 3.32%.

[0149] <Example 53> Synthesis of Component A-53 [ka] (1) Synthesis of compound 72: Synthesis is performed according to the method disclosed in the references James F. Cameron.; Jean MJ Frechet. J. Am. Chem. Soc. 1991, 113, 4303.

[0150] (2) Synthesis of Compound 73: Compound 73 (yield 73%) was produced using Compound 72 as a starting material according to the method of Example 52. 1 H NMR (400mHz, CDCl3): δ=7.71 (s, 1H), 7.22 (s, 1H), 4.66 (m, 1H), 4.13 (t, J=6.1 Hz, 2H), 3.99 (s, 3H), 3.32 (dd, J=11.6, 5.7 Hz, 2H), 2.82 (t, J=5.9 Hz, 2H), 2.44 (t, J=7.2 Hz, 2H), 2.26 - 2.17 (m, 2H), 1.33 (d, J=6.9 Hz, 3H). MS (ESI): [M+H] 404.0863. (3) Synthesis of Compound 74: Compound 74 (yield 70%) was produced from Compound 73 according to the method of Example 52. 1 H NMR (400mHz, CDCl3): δ=7.71 (s, 1H), 7.22 (s, 1H), 4.86 (m, 1H), 4.42 (m, 1H), 4.13 (t, J=6.1 Hz, 2H), 3.99 (s, 3H), 3.95 (s, 3H), 3.43 (d, J=5.6, 2H), 3.32 (dd, J=11.6, 5.7 Hz, 2H), 2.82 (t, J=5.9 Hz, 2H), 2.44 (t, J=7.2 Hz, 2H), 2.26 - 2.17 (m, 2H), 1.42 (s, 9H), 1.33 (d, J=6.9 Hz, 3H).MS (ESI): [M+H] 559.2402. (4) Synthesis of component A-53: Hyaluronic acid (2g, 340kDa) was dissolved in 100mL 0.01mol / L 2-(N-morpholine)ethanesulfonic acid MES buffer (pH=5.2), stirred until completely dissolved, compound 74 (112mg, 0.2mmol) was weighed and dissolved in 10mL dimethylsulfoxide DMSO, then added to the reaction solution, 4-(4,6-dimethoxytriazin-2-yl)-4-methylmorpholine hydrochloride DMTMM (0.4g, 1.5mmol) was weighed and dissolved in 3mL MES buffer, added to the reaction solution three times (once every hour), and reacted at 35°C for 24 hours. After that, the reaction solution was placed in a dialysis bag (MWCO 7000), dialyzed with deionized water for 2-3 days, and freeze-dried to obtain photosensitive hyaluronic acid derivative A-53 (1.75g). 1 The labeling rate of compound 74 was calculated to be about 2.34% based on the H-NMR spectrum.

[0151] <Example 54> Synthesis of Component A-54 [ka] (1) Synthesis of Compound 75: The synthesis is carried out according to the method disclosed in the references Jack E. Baldwin.; Adrian W. McConnaughie.; Sung Bo Shin. Tetrahedron. 1990, 46, 6879.

[0152] (2) Synthesis of Compound 76: Compound 76 (yield 64%) was produced from Compound 75 according to the method of Example 52. 1H NMR (400mHz, CDCl3): δ=7.71 (s, 1H), 7.75 (ddd, J=8.2, 1.4, 0.4 Hz, 1H), 7.22 (s, 1H), 7.57 (tdd, J=7.3, 1.4, 0.7 Hz, 1H), 7.49 (dd, J=7.9, 1.4 Hz, 1H), 7.36 (ddd, J=8.1, 7.3, 1.4 Hz, 1H), 4.66 (s, 1H), 4.13 (t, J=6.1 Hz, 2H), 3.99 (s, 3H), 3.32 (dd, J=11.6, 5.7 Hz, 2H), 2.82 (t, J=5.9 Hz, 2H), 2.44 (t, J=7.2 Hz, 2H), 2.26 - 2.17 (m, 2H). MS (ESI): [M+H] 511.0881.

[0153] (3) Synthesis of compound 77: The method of Example 52 was used, compound 76 was used as a raw material, and compound 77 (yield 58%) was used. 1 H NMR (400mHz, CDCl3): δ=7.71 (s, 1H), 7.75 (ddd, J=8.2, 1.4, 0.4 Hz, 1H), 7.22 (s, 1H), 7.57 (tdd, J=7.3, 1.4, 0.7 Hz, 1H), 7.49 (dd, J=7.9, 1.4 Hz, 1H), 7.36 (ddd, J=8.1, 7.3, 1.4 Hz, 1H), 4.86 (s, 1H), 4.42 (m, 1H), 4.13 (t, J=6.1 Hz, 2H), 3.99 (s, 3H), 3.95 (s, 3H), 3.43 (d, J=5.6, 2H), 3.32 (dd, J=11.6, 5.7 Hz, 2H), 2.82 (t, J=5.9 Hz, 2H), 2.44 (t, J=7.2 Hz, 2H), 2.26 - 2.17 (m, 2H),1.42 (s, 9H). MS (ESI): [M+H] 666.2423. (4) Synthesis of component A-54: Hyaluronic acid (2g, 340kDa) was dissolved in 100mL 0.01mol / L 2-(N-morpholine)ethanesulfonic acid MES buffer (pH=5.2), stirred until completely dissolved, compound 77 (133mg, 0.2mmol) was weighed and dissolved in 10mL dimethylsulfoxide DMSO, then added to the reaction solution, 4-(4,6-dimethoxytriazin-2-yl)-4-methylmorpholine hydrochloride DMTMM (0.4g, 1.5mmol) was weighed and dissolved in 3mL MES buffer, added to the reaction solution three times (once every hour), and reacted at 35°C for 24 hours. After that, the reaction solution was placed in a dialysis bag (MWCO 7000), dialyzed with deionized water for 2-3 days, and freeze-dried to obtain photosensitive hyaluronic acid derivative A-54 (1.8g). 1 The labeling rate of compound 77 calculated based on the H-NMR spectrum was approximately 3.35%.

[0154] <Example 55> Synthesis of Component A-55 [ka] (1) Synthesis of compound 78: Synthesis is performed according to the method disclosed in the references Pauloehrl, T.; Delaittre, G.; Bruns, M.; Meiβler, M.; Bοrner, HG; Bastmeyer, M.; Barner-Kowollik, C. Angew. Chem. Int. Ed. 2012, 51, 9181. 1H NMR (400mHz, CDCl3): δ=7.71 (s, 1H), 7.22 (s, 1H), 4.76 (s, 2H), 4.13 (t, J=6.1 Hz, 2H), 3.99 (s, 3H), 3.90 - 3.80 (m, 1H), 3.63 - 3.52(m, 1H), 3.32 (dd, J=11.6, 5.7 Hz, 2H), 2.82 (t, J=5.9 Hz, 2H), 2.44 (t, J=7.2 Hz, 2H), 2.26 - 2.17 (m, 2H), 2.00 - 1.34 (m, 6H). MS (ESI): [M+H] 428.1831. (2) Synthesis of component A-55: Hyaluronic acid (2g, 340kDa) was dissolved in 100mL 0.01mol / L 2-(N-morpholine)ethanesulfonic acid MES buffer (pH=5.2), stirred until completely dissolved, compound 78 (85mg, 0.2mmol) was weighed and dissolved in 10mL dimethylsulfoxide DMSO, then added to the reaction solution, 4-(4,6-dimethoxytriazin-2-yl)-4-methylmorpholine hydrochloride DMTMM (0.4g, 1.5mmol) was weighed and dissolved in 3mL MES buffer, added to the reaction solution three times (once every hour), and reacted at 35°C for 24 hours. After that, the reaction solution was placed in a dialysis bag (MWCO 7000), dialyzed with deionized water for 2-3 days, and freeze-dried to obtain photosensitive hyaluronic acid derivative A-55 (1.89g). 1 The labeling rate of compound 78 was calculated to be about 3.42% based on the H-NMR spectrum.

[0155] <Example 56> Synthesis of Component A-56 [ka] (1) Synthesis of compound 79: The synthesis is carried out according to the method disclosed in the references Patchornik Abraham.; Amit B.; Woodward RBJ Am. Chem. Soc. 1970, 92, 6333. 1H NMR (400mHz, CDCl3):δ=8.02 - 7.23 (m, 5H), 7.71 (s, 1H), 7.22 (s, 1H), 4.76 (s, 2H), 4.13 (t, J=6.1 Hz, 2H), 3.99 (s, 3H), 3.32 (dd, MS (ESI): [M+H] 448.1561. (2) Synthesis of component A-56: Hyaluronic acid (2g, 340kDa) was dissolved in 100mL 0.01mol / L 2-(N-morpholine)ethanesulfonic acid MES buffer (pH=5.2), stirred until completely dissolved, compound 79 (89mg, 0.2mmol) was weighed and dissolved in 10mL dimethylsulfoxide DMSO, then added to the reaction solution, 4-(4,6-dimethoxytriazin-2-yl)-4-methylmorpholine hydrochloride DMTMM (0.4g, 1.5mmol) was weighed and dissolved in 3mL MES buffer, added to the reaction solution three times (once every hour), and reacted at 35°C for 24 hours. After that, the reaction solution was placed in a dialysis bag (MWCO 7000), dialyzed with deionized water for 2-3 days, and freeze-dried to obtain photosensitive hyaluronic acid derivative A-56 (1.87g). 1 The labeling rate of compound 79 calculated based on the H-NMR spectrum was approximately 3.21%.

[0156] <Example 57> Synthesis of Component A-57 [ka] (1) Synthesis of compound 80: The synthesis is carried out according to the method disclosed in the references Patchornik Abraham.; Amit B.; Woodward RBJ Am. Chem. Soc. 1970, 92, 6333. 1H NMR (400mHz, CDCl3): δ=7.71 (s, 1H), 7.22 (s, 1H), 4.76 (s, 2H), 4.25 (q, J=6.5 Hz, 2H), 4.13 (t, J=6.1 Hz, 2H), 3.99 (s, 3H), 3.32 (dd, J=11.6, 5.7 Hz, 2H),2.82 (t, J=5.9 Hz, 2H), 2.44 (t, J=7.2 Hz, 2H), 2.26 - 2.17 (m, 2H), 1.32 (t, J=6.5 Hz, 3H). MS (ESI): [M+H] 416.1432. (2) Synthesis of component A-57: Hyaluronic acid (2g, 340kDa) was dissolved in 100mL 0.01mol / L 2-(N-morpholine)ethanesulfonic acid MES buffer (pH=5.2), stirred until completely dissolved, compound 80 (83mg, 0.2mmol) was weighed and dissolved in 10mL dimethylsulfoxide DMSO, then added to the reaction solution, 4-(4,6-dimethoxytriazin-2-yl)-4-methylmorpholine hydrochloride DMTMM (0.4g, 1.5mmol) was weighed and dissolved in 3mL MES buffer, added to the reaction solution three times (once every hour), and reacted at 35°C for 24 hours. After that, the reaction solution was placed in a dialysis bag (MWCO 7000), dialyzed with deionized water for 2-3 days, and freeze-dried to obtain photosensitive hyaluronic acid derivative A-57 (1.74g). 1 The labeling rate of compound 80 calculated based on the H-NMR spectrum was approximately 2.34%.

[0157] <Example 58> Synthesis of Component A-58 [ka] (1) Synthesis of Compound 81: The synthesis is carried out according to the method disclosed in the references Kalbag, SM; Roeske, RWJ Am. Chem. Soc. 1975, 97, 440. 1H NMR (400mHz, CDCl3): δ =7.71 (s, 1H), 7.22 (s, 1H), 4.76 (s, 2H), 4.63 (q, J=6.9 Hz, 1H), 4.13 (t, J=6.1 Hz, 2H), 3.99 (s, 3H), 3.67 MS (ESI): [M+H] 473.1734. (2) Synthesis of component A-58: Hyaluronic acid (2g, 340kDa) was dissolved in 100mL 0.01mol / L 2-(N-morpholine)ethanesulfonic acid MES buffer (pH=5.2), stirred until completely dissolved, compound 81 (94mg, 0.2mmol) was weighed and dissolved in 10mL dimethylsulfoxide DMSO, then added to the reaction solution, 4-(4,6-dimethoxytriazin-2-yl)-4-methylmorpholine hydrochloride DMTMM (0.4g, 1.5mmol) was weighed and dissolved in 3mL MES buffer, added to the reaction solution three times (once every hour), and reacted at 35°C for 24 hours. After that, the reaction solution was placed in a dialysis bag (MWCO 7000), dialyzed with deionized water for 2-3 days, and freeze-dried to obtain photosensitive hyaluronic acid derivative A-58 (1.72g). 1 The labeling rate of compound 81 calculated based on the H-NMR spectrum was approximately 2.56%.

[0158] <Example 59> Synthesis of Component A-59 [ka] (1) Synthesis of compound 82: The synthesis is carried out according to the method disclosed in the references Patchornik Abraham.; Amit B.; Woodward RBJ Am. Chem. Soc. 1970, 92, 6333. 1H NMR (400mHz, CDCl3): δ=7.71 (s, 1H), 7.22 (s, 1H), 4.76 (s, 2H), 4.25 (q, J=6.5 Hz, 2H), 4.13 (t, J=6.1 Hz, 2H), 3.99 (s, 3H), 3.32 (dd, J=11.6, 5.7 Hz, 2H),2.82 (t, J=5.9 Hz, 2H), 2.44 (t, J=7.2 Hz, 2H), 2.26 - 2.17 (m, 2H), 1.32 (t, J=6.5 Hz, 3H). MS (ESI): [M+H] 432.1224. (2) Synthesis of component A-59: Hyaluronic acid (2g, 340kDa) was dissolved in 100mL 0.01mol / L 2-(N-morpholine)ethanesulfonic acid MES buffer (pH=5.2), stirred until completely dissolved, compound 82 (83mg, 0.2mmol) was weighed and dissolved in 10mL dimethylsulfoxide DMSO, then added to the reaction solution, 4-(4,6-dimethoxytriazin-2-yl)-4-methylmorpholine hydrochloride DMTMM (0.4g, 1.5mmol) was weighed and dissolved in 3mL MES buffer, added to the reaction solution three times (once every hour), and reacted at 35°C for 24 hours. After that, the reaction solution was placed in a dialysis bag (MWCO 7000), dialyzed with deionized water for 2-3 days, and freeze-dried to obtain photosensitive hyaluronic acid derivative A-59 (1.74g). 1 The labeling rate of compound 82 was calculated to be about 2.34% based on the H-NMR spectrum.

[0159] <Example 60> Synthesis of Component A-60 [ka] (1) Synthesis of Compound 83: The synthesis is carried out according to the method disclosed in Engels, J.; Schlaeger, EJJ Med. Chem. 1977, 20, 907. 1H NMR (400mHz, CDCl3): δ=7.71 (s, 1H), 7.22 (s, 1H), 4.76 (s, 2H), 4.25 (q, J=6.5 Hz, 2H), 4.13 (t, J=6.1 Hz, 2H), 3.99 (s, 3H), 3.32 (dd, J=11.6, 5.7 Hz, 2H),2.82 (t, J=5.9 Hz, 2H), 2.44 (t, J=7.2 Hz, 2H), 2.26 - 2.17 (m, 2H), 1.32 (t, J=6.5 Hz, 3H). MS (ESI): [M+H] 451.1126. (2) Synthesis of component A-60: Hyaluronic acid (2g, 340kDa) was dissolved in 100mL 0.01mol / L 2-(N-morpholine)ethanesulfonic acid MES buffer (pH=5.2), stirred until completely dissolved, compound 83 (90mg, 0.2mmol) was weighed and dissolved in 10mL dimethylsulfoxide DMSO, then added to the reaction solution, 4-(4,6-dimethoxytriazin-2-yl)-4-methylmorpholine hydrochloride DMTMM (0.4g, 1.5mmol) was weighed and dissolved in 3mL MES buffer, added to the reaction solution three times (once every hour), and reacted at 35°C for 24 hours. After that, the reaction solution was placed in a dialysis bag (MWCO 7000), dialyzed with deionized water for 2-3 days, and freeze-dried to obtain photosensitive hyaluronic acid derivative A-60 (1.72g). 1 The labeling rate of compound 83 calculated based on the H-NMR spectrum was approximately 2.36%.

[0160] <Example 62> Synthesis of Component A-62 [ka] (1) Synthesis of compound 85: The synthesis is carried out according to the method disclosed in the references Grazyna Groszek.; Agnieszka Nowak-Krol.; Barbara Filipek. Eur. J. Med. Chem. 2009, 44, 5103. 1H NMR (400mHz, CDCl3): δ=8.04 (s, 1H), 7.42 (s, 1H), 4.76 (s, 2H), 4.42 (m, 1H), 4.13 (t, J=6.1 Hz, 2H), 3.99 (s, 3H), 3.95 (s, 3H), 3.43 (d, J=5.6, 2H), 3.32 (dd, J=11.6, 5.7 Hz, 2H), 2.82 (t, J=5.9 Hz, 2H), 2.44 (t, J=7.2 Hz, 2H), 2.26 - 2.17 (m, 2H),1.42 (s, 9H). MS (ESI): [M+H] 545.2234. (2) Synthesis of component A-62: Hyaluronic acid (2g, 340kDa) was dissolved in 100mL 0.01mol / L 2-(N-morpholine)ethanesulfonic acid MES buffer (pH=5.2), stirred until completely dissolved, compound 85 (109mg, 0.2mmol) was weighed and dissolved in 10mL dimethylsulfoxide DMSO, then added to the reaction solution, 4-(4,6-dimethoxytriazin-2-yl)-4-methylmorpholine hydrochloride DMTMM (0.4g, 1.5mmol) was weighed and dissolved in 3mL MES buffer, added to the reaction solution three times (once every hour), and reacted at 35°C for 24 hours. After that, the reaction solution was placed in a dialysis bag (MWCO 7000), dialyzed with deionized water for 2-3 days, and freeze-dried to obtain photosensitive hyaluronic acid derivative A-62 (1.92g). 1 The labeling rate of compound 85 calculated based on the H-NMR spectrum was approximately 3.14%.

[0161] <Example 63> Synthesis of Component A-63 [ka] (1) Synthesis of compound 86: Synthesis is performed according to the method disclosed in the references Thomas F. Greene.; Shu Wang.; Mary J. Meegan. J. Med. Chem. 2016, 59, 90. 1H NMR (400mHz, CDCl3): δ=7.95 (s, 1H), 7.12 (s, 1H), 4.76 (s, 2H), 4.42 (m, 1H),4.13 (t, J=6.1 Hz, 2H), 3.99 (s, 3H), 3.95 (s, 3H), 3.43 (d, J=5.6, 2H), 3.32 (dd, J=11.6, 5.7 Hz, 2H), 2.82 (t, J=5.9 Hz, 2H), 2.44 (t, J=7.2 Hz, 2H), 2.26 - 2.17 (m, 2H),1.42 (s, 9H). MS (ESI): [M+H] 545.2262. (2) Synthesis of component A-63: Hyaluronic acid (2g, 340kDa) was dissolved in 100mL 0.01mol / L 2-(N-morpholine)ethanesulfonic acid MES buffer (pH=5.2), stirred until completely dissolved, compound 86 (109mg, 0.2mmol) was weighed and dissolved in 10mL dimethylsulfoxide DMSO, then added to the reaction solution, 4-(4,6-dimethoxytriazin-2-yl)-4-methylmorpholine hydrochloride DMTMM (0.4g, 1.5mmol) was weighed and dissolved in 3mL MES buffer, added to the reaction solution three times (once every hour), and reacted at 35°C for 24 hours. After that, the reaction solution was placed in a dialysis bag (MWCO 7000), dialyzed with deionized water for 2-3 days, and freeze-dried to obtain photosensitive hyaluronic acid derivative A-63 (1.88g). 1 The labeling rate of compound 86 was calculated to be about 3.45% based on the H-NMR spectrum.

[0162] <Example 64> Synthesis of Component A-64 [ka] (1) Synthesis of compound 87: Synthesis is performed according to the method disclosed in the references Yu-Shan.; Mohane Selvaraj Coumar.; Hsing-Pang Hsieh. J. Med. Chem. 2009, 52, 4941. 1H NMR (400mHz, CDCl3): δ=7.64 (s, 1H), 7.02 (s, 1H), 4.76 (s, 2H), 4.42 (m, 1H),4.13 (t, J=6.1 Hz, 2H), 3.99 (s, 3H), 3.95 (s, 3H), 3.43 (d, J=5.6, 2H), 3.32 (dd, J=11.6, 5.7 Hz, 2H), 2.82 (t, J=5.9 Hz, 2H), 2.44 (t, J=7.2 Hz, 2H), 2.26 - 2.17 (m, 2H),1.42 (s, 9H). MS (ESI): [M+H] 545.2231. (2) Synthesis of component A-64: Hyaluronic acid (2g, 340kDa) was dissolved in 100mL 0.01mol / L 2-(N-morpholine)ethanesulfonic acid MES buffer (pH=5.2), stirred until completely dissolved, compound 87 (109mg, 0.2mmol) was weighed and dissolved in 10mL dimethylsulfoxide DMSO, then added to the reaction solution, 4-(4,6-dimethoxytriazin-2-yl)-4-methylmorpholine hydrochloride DMTMM (0.4g, 1.5mmol) was weighed and dissolved in 3mL MES buffer, added to the reaction solution three times (once every hour), and reacted at 35°C for 24 hours. After that, the reaction solution was placed in a dialysis bag (MWCO 7000), dialyzed with deionized water for 2-3 days, and freeze-dried to obtain photosensitive hyaluronic acid derivative A-64 (1.85g). 1 The labeling rate of compound 87 calculated based on the H-NMR spectrum was approximately 3.32%.

[0163] <Example 65> Synthesis of Component A-65 [ka] Synthesis of component A-65: Hyaluronic acid (2g, 340kDa) was dissolved in 100mL 0.01mol / L 2-(N-morpholine)ethanesulfonic acid MES buffer solution (pH=5.2), stirred until completely dissolved, NB mixture (compound 68 / compound 71, 60mg, mass ratio 1:1) was weighed and dissolved in 10mL dimethylsulfoxide DMSO, then added to the reaction solution, 4-(4,6-dimethoxytriazin-2-yl)-4-methylmorpholine hydrochloride DMTMM (0.4g, 1.5mmol) was weighed and dissolved in 3mL MES buffer solution, added to the reaction solution in three portions (once every hour), and reacted at 35°C for 24 hours. Thereafter, the reaction solution was placed in a dialysis bag (MWCO 7000), dialyzed against deionized water for 2-3 days, and freeze-dried to obtain photosensitive hyaluronic acid derivative A-65 (1.89 g). 1 The labeling rate of the NB mixture (compound 68 / compound 71) calculated based on the H-NMR spectrum was approximately 3.41%.

[0164] <Example 66> Synthesis of Component A-66 [ka] Synthesis of component A-66: Carboxymethyl cellulose (2 g, 340 kDa) was dissolved in 100 mL 0.01 mol / L 2-(N-morpholine)ethanesulfonic acid MES buffer (pH = 5.2), stirred until completely dissolved, weighed out compound 71 (109 mg, 0.2 mmol) and dissolved in 10 mL dimethyl sulfoxide DMSO, then added to the reaction solution, weighed out 4-(4,6-dimethoxytriazin-2-yl)-4-methylmorpholine hydrochloride DMTMM (0.4 g, 1.5 mmol) and dissolved in 3 mL MES buffer, added to the reaction solution three times (once every hour), and reacted at 35 ° C for 24 hours. Then, the reaction solution was placed in a dialysis bag (MWCO 7000), dialyzed with deionized water for 2-3 days, and freeze-dried to obtain photosensitive carboxymethyl cellulose derivative A-66 (1.74 g). 1The labeling rate of compound 71 calculated based on the H-NMR spectrum was approximately 2.34%.

[0165] <Example 67> Synthesis of Component A-67 [ka] (1) Synthesis of Compound 88: Compound 88 was prepared by conventional chemical means according to the method of Example 52. 1 H NMR (400mHz, CDCl3): δ=7.71 (s, 1H), 7.22 (s, 1H), 4.76 (s, 2H), 4.42 (m, 1H),4.13 (t, J=6.1 Hz, 2H), 3.99 (s, 3H), 3.95 (s, 3H), 3.43 (d, J=5.6, 2H), 2.44 (t, J=7.2 Hz, 2H), 2.26 - 2.17 (m, 2H),1.42 (s, 9H). MS (ESI): [M+H] 503.1732. (2) Synthesis of component A-67: 1 g of chitosan was added to 75 mL of isopropanol to form a chitosan suspension, and then compound 88 (0.2 g, 0.40 mmol), EDC-HCl (0.76 g, 3.96 mmol) and NHS (0.46 g, 4.0 mmol) were added to the solution in that order, and the mixture was reacted at room temperature for 48 hours while stirring. After the reaction was completed, the mixture was dialyzed against a dilute hydrochloric acid solution (pH=3.5) containing sodium chloride for one day, and then further dialyzed against pure water for one day, and freeze-dried to obtain photosensitive chitosan derivative A-67 (0.89 g). 1 The degree of modification of compound 88 was calculated to be about 12.5% ​​based on the H-NMR spectrum.

[0166] <Example 68> Synthesis of Component A-68 [ka] (1) Synthesis of Compound 89: Compound 89 was prepared by conventional chemical means according to the method of Example 52. 1H NMR (400mHz, CDCl3): δ=7.71 (s, 1H), 7.22 (s, 1H), 4.76 (s, 2H), 4.42 (m, 1H),4.13 (t, J=6.1 Hz, 2H), 3.99 (s, 3H), 3.95 (s, 3H), 3.43 (d, J=5.6, 2H), 3.04 (t, J=7.2 Hz, 2H),1.42 (s, 9H). MS (ESI): [M+H] 523.0731. (2) Synthesis of component A-68: PEG-4OH (1g, 0.05mmol) was dissolved in anhydrous acetonitrile, K2CO3 (55.3mg, 0.4mmol) was added, and the mixture was stirred for 30 minutes. Compound 89 (0.20g, 0.4mmol) was then added and the mixture was allowed to react at room temperature for 24 hours. After the reaction was completed, most of the solvent was removed, the mixture was reprecipitated in diethyl ether, washed several times, filtered by suction, and dried to obtain photosensitive polyethylene glycol derivative A-68 (0.85g). 1 The degree of modification of compound 89 was calculated to be approximately 95% based on the H-NMR spectrum.

[0167] <Example 69> Synthesis of Component A-69 [ka] (1) Synthesis of Compound 90: Compound 89 (0.5 g, 1.29 mmol) and ethylene glycol (0.24 g, 3.87 mmol) were dissolved in anhydrous acetonitrile, K2CO3 (0.5 g, 3.87 mmol) was added as a base, and the mixture was allowed to react overnight under reflux. After the reaction was completed, the solvent was removed by rotary evaporation under reduced pressure, and compound 90 (0.34 g, 72%) was obtained by column purification.

[0168] (2) Synthesis of Compound 91: Compound 90 (0.64 g, 1.72 mmol) and triethylamine (0.34 g, 3.44 mmol) were dissolved in dry dichloromethane, and methacryloyl chloride (0.27 g, 2.58 mmol) was slowly added dropwise to the solution under ice bath conditions. After the addition was completed, the mixture was allowed to react overnight at room temperature. After the reaction was completed, the solvent was removed by rotary evaporation under reduced pressure, and compound 91 (0.49 g, 65%) was obtained by column purification. 1 H NMR (400mHz, CDCl3): δ=7.71 (s, 1H), 7.22 (s, 1H), 6.25 (s, 1H), 5.68 (s, 1H), 4.76 (s, 2H), 4.42 (m, 1H),4.13 (t, J=6.1 Hz, 2H), 3.99 (s, 3H), 3.95 (s, 3H), 3.79 (t, J=6.1 Hz, 2H), 3.70 (t, J=7.2 Hz, 2H), 3.56 (t, J=7.2 Hz, 2H), 3.43 (d, J=5.6, 2H), 1.87 (s, 3H),1.42 (s, 9H). MS (ESI): [M+H] 573.2125. (3) Synthesis of component A-69: Compound 91 (0.28 g, 0.63 mmol), comonomer PEG-MA (0.882 g, 2.52 mmol) and initiator azobisisobutyronitrile (11 mg) were weighed and added to a Schreck flask, dissolved by adding anhydrous THF, and treated by multiple cycles of freezing and vacuuming. The reaction system was reacted for 24 hours at 75°C. After the reaction was completed, the reaction solution was put into cold diethyl ether and purified by multiple reprecipitations to obtain photosensitive copolymer derivative A-69 (0.86 g). 1 The content of compound 91 in the copolymer was calculated to be about 15.3% based on the H-NMR spectrum. The molecular weight of the synthetic polymer measured by GPC was about 25 kDa. As a result of calculation based on the blending ratio, n was 12, x was 10, and y was 40.

[0169] <Example 70> Synthesis of Component A-70 [ka] (1) Synthesis of Compound 92: The compound is synthesized according to the method disclosed in the references Takahiro Muraoka.; Honggang Cui.; Samuel I. Stupp. J. Am. Chem. Soc. 2008, 130, 2946. 1 H NMR (400mHz, CDCl3): δ=7.71 (s, 1H), 7.22 (s, 1H), 4.35 (s, 2H), 4.13 (t, J=6.1 Hz, 2H), 3.99 (s, 3H), 3.32 (dd, J=11.6, 5.7 Hz, 2H), 2.82 (t, J=5.9 Hz, 2H), 2.44 (t, J=7.2 Hz, 2H), 2.26 - 2.17 (m, 2H). MS (ESI): [M+H] 327.1617. (2) Synthesis of component A-70: Hyaluronic acid (2g, 340kDa) was dissolved in 100mL 0.01mol / L 2-(N-morpholine)ethanesulfonic acid MES buffer (pH=5.2), stirred until completely dissolved, compound 92 (65mg, 0.2mmol) was weighed and dissolved in 10mL dimethylsulfoxide DMSO, then added to the reaction solution, 4-(4,6-dimethoxytriazin-2-yl)-4-methylmorpholine hydrochloride DMTMM (0.4g, 1.5mmol) was weighed and dissolved in 3mL MES buffer, added to the reaction solution three times (once every hour), and reacted at 35°C for 24 hours. After that, the reaction solution was placed in a dialysis bag (MWCO 7000), dialyzed with deionized water for 2-3 days, and freeze-dried to obtain photosensitive hyaluronic acid derivative A-70 (1.8g). 1 The labeling rate of compound 92 was calculated to be about 3.26% based on the H-NMR spectrum.

[0170] <Example 71> Synthesis of Component A-71 [ka] (1) Synthesis of Compound 93: The compound is synthesized according to the method disclosed in the references Takahiro Muraoka.; Honggang Cui.; Samuel I. Stupp. J. Am. Chem. Soc. 2008, 130, 2946.

[0171] (2) Synthesis of Compound 94: Compound 93 (15.4 g, 36.24 mmol) was dissolved in 100 mL methanol, and methylaminoacetic acid (7.0 g, 78.65 mmol) was dissolved in 70 mL methanol and an aqueous solution of NaOH (2 M, 50 mL) was added dropwise to the solution. The mixture was reacted for 30 minutes with stirring at room temperature, and then NaBH4 (12 g, 317.2 mmol) was slowly added dropwise at 0° C. After reacting for 2 hours, the solvent was removed by rotary evaporation, and then the pH was adjusted to about 5 with 2 M HCl to precipitate a white solid, which was washed several times with diethyl ether. The resulting crude product was reprecipitated with diethyl ether to obtain Compound 94 (17.5 g, 97%). 1 H NMR (400mHz, CDCl3): δ=7.71 (s, 1H), 7.22 (s, 1H), 4.55 (s, 2H), 4.13 (t, J=6.1 Hz, 2H), 3.99 (s, 3H), 3.95 (s, 3H), 3.74 (s, 2H), 3.32 (dd, J=11.6, 5.7 Hz, 2H), 2.82 (t, J=5.9 Hz, 2H), 2.44 (t, J=7.2 Hz, 2H), 2.26 - 2.17 (m, 2H),1.42 (s, 9H). MS (ESI): [M+H] 499.2442.

[0172] (3) Synthesis of Compound 95: Compound 94 (15 g, 30 mmol) was dissolved in a mixed solution of dichloromethane / trifluoroacetic acid (3:1) and reacted at room temperature for 30 minutes with stirring. The solvent was then removed by rotary evaporation, and the resulting crude product was reprecipitated with diethyl ether to give Compound 95 (11.4 g, 95%). 1H NMR (400mHz, CDCl3): δ=7.71 (s, 1H), 7.22 (s, 1H), 4.55 (s, 2H), 4.13 (t, J=6.1 Hz, 2H), 3.99 (s, 3H), 3.95 (s, 3H), 3.74 (s, 2H), 3.32 (dd, J=11.6, 5.7 Hz, 2H), 2.82 (t, J=5.9 Hz, 2H), 2.44 (t, J=7.2 Hz, 2H), 2.26 - 2.17 (m, 2H). MS (ESI): [M+H] 399.1823. (4) Synthesis of component A-71: Hyaluronic acid (2g, 340kDa) was dissolved in 100mL 0.01mol / L 2-(N-morpholine)ethanesulfonic acid MES buffer (pH=5.2), stirred until completely dissolved, compound 95 (80mg, 0.2mmol) was weighed and dissolved in 10mL dimethylsulfoxide DMSO, then added to the reaction solution, 4-(4,6-dimethoxytriazin-2-yl)-4-methylmorpholine hydrochloride DMTMM (0.4g, 1.5mmol) was weighed and dissolved in 3mL MES buffer, added to the reaction solution three times (once every hour), and reacted at 35°C for 24 hours. After that, the reaction solution was placed in a dialysis bag (MWCO 7000), dialyzed with deionized water for 2-3 days, and freeze-dried to obtain photosensitive hyaluronic acid derivative A-71 (1.87g). 1 The labeling rate of compound 95 calculated based on the H-NMR spectrum was approximately 3.42%.

[0173] <Example 72> Synthesis of Component A-72 [ka] (1) Synthesis of Compound 96: The synthesis is carried out according to the method disclosed in the references James F. Cameron.; Jean MJ Frechet. J. Am. Chem. Soc. 1991, 113, 4303. 1H NMR (400mHz, CDCl3): δ=7.71 (s, 1H), 7.22 (s, 1H), 4.75 (m, 1H), 4.13 (t, J=6.1 Hz, 2H), 3.99 (s, 3H), 3.95 (s, 3H), 3.74 (s, 2H), 3.32 (dd, J=11.6, 5.7 Hz, 2H), 2.82 (t, J=5.9 Hz, 2H), 2.44 (t, J=7.2 Hz, 2H), 2.26 - 2.17 (m, 2H), 1.33 (d, J=6.9 Hz, 3H). MS (ESI): [M+H] 413.2041. (2) Synthesis of component A-72: Hyaluronic acid (2g, 340kDa) was dissolved in 100mL 0.01mol / L 2-(N-morpholine)ethanesulfonic acid MES buffer (pH=5.2), stirred until completely dissolved, compound 96 (82mg, 0.2mmol) was weighed and dissolved in 10mL dimethylsulfoxide DMSO, then added to the reaction solution, 4-(4,6-dimethoxytriazin-2-yl)-4-methylmorpholine hydrochloride DMTMM (0.4g, 1.5mmol) was weighed and dissolved in 3mL MES buffer, added to the reaction solution three times (once every hour), and reacted at 35°C for 24 hours. After that, the reaction solution was placed in a dialysis bag (MWCO 7000), dialyzed with deionized water for 2-3 days, and freeze-dried to obtain photosensitive hyaluronic acid derivative A-72 (1.84g). 1 The labeling rate of compound 96 calculated based on the H-NMR spectrum was approximately 3.21%.

[0174] <Example 74> Synthesis of Component A-74 [ka] (1) Synthesis of compound 98: Synthesis is performed according to the method disclosed in the references Pauloehrl, T.; Delaittre, G.; Bruns, M.; Meiβler, M.; Bοrner, HG; Bastmeyer, M.; Barner-Kowollik, C. Angew. Chem. Int. Ed. 2012, 51, 9181. 1 H NMR (400mHz, CDCl3): δ=7.71 (s, 1H), 7.22 (s, 1H), 4.55 (s, 2H), 4.13 (t, J=6.1 Hz, 2H), 3.99 (s, 3H), 3.90 - 3.80 (m, 1H), 3.63 - 3.52(m, 1H), 3.32 (dd, J=11.6, 5.7 Hz, 2H), 2.82 (t, J=5.9 Hz, 2H), 2.44 (t, J=7.2 Hz, 2H), 2.26 - 2.17 (m, 2H), 2.00 - 1.34 (m, 6H). MS (ESI): [M+H] 411.2231. (2) Synthesis of component A-74: Hyaluronic acid (2g, 340kDa) was dissolved in 100mL 0.01mol / L 2-(N-morpholine)ethanesulfonic acid MES buffer (pH=5.2), stirred until completely dissolved, compound 98 (82mg, 0.2mmol) was weighed and dissolved in 10mL dimethylsulfoxide DMSO, then added to the reaction solution, 4-(4,6-dimethoxytriazin-2-yl)-4-methylmorpholine hydrochloride DMTMM (0.4g, 1.5mmol) was weighed and dissolved in 3mL MES buffer, added to the reaction solution three times (once every hour), and reacted at 35°C for 24 hours. After that, the reaction solution was placed in a dialysis bag (MWCO 7000), dialyzed with deionized water for 2-3 days, and freeze-dried to obtain photosensitive hyaluronic acid derivative A-74 (1.88g). 1 The labeling rate of compound 98 was calculated to be about 3.38% based on the H-NMR spectrum.

[0175] <Example 75> Synthesis of Component A-75 [ka] (1) Synthesis of Compound 99: The synthesis is carried out according to the method disclosed in the references Patchornik Abraham.; Amit B.; Woodward RBJ Am. Chem. Soc. 1970, 92, 6333. 1 H NMR (400mHz, CDCl3): δ=8.02 - 7.23 (m, 5H), 7.71 (s, 1H), 7.22 (s, 1H), 4.55 (m, 1H), 4.13 (t, J=6.1 Hz, 2H), 3.99 (s, 3H), 3.32 (dd, MS (ESI): [M+H] 431.1926. (2) Synthesis of component A-75: Hyaluronic acid (2g, 340kDa) was dissolved in 100mL 0.01mol / L 2-(N-morpholine)ethanesulfonic acid MES buffer (pH=5.2), stirred until completely dissolved, compound 99 (86mg, 0.2mmol) was weighed and dissolved in 10mL dimethylsulfoxide DMSO, then added to the reaction solution, 4-(4,6-dimethoxytriazin-2-yl)-4-methylmorpholine hydrochloride DMTMM (0.4g, 1.5mmol) was weighed and dissolved in 3mL MES buffer, added to the reaction solution three times (once every hour), and reacted at 35°C for 24 hours. After that, the reaction solution was placed in a dialysis bag (MWCO 7000), dialyzed with deionized water for 2-3 days, and freeze-dried to obtain photosensitive hyaluronic acid derivative A-75 (1.85g). 1 The labeling rate of compound 99 calculated based on the H-NMR spectrum was approximately 3.21%.

[0176] <Example 76> Synthesis of Component A-76 [ka] (1) Synthesis of Compound 100: The synthesis is carried out according to the method disclosed in the references Patchornik Abraham.; Amit B.; Woodward RBJ Am. Chem. Soc. 1970, 92, 6333. 1 H NMR (400mHz, CDCl3): δ=7.71 (s, 1H), 7.22 (s, 1H), 4.55 (s, 2H), 4.25 (q, J=6.5 Hz, 2H), 4.13 (t, J=6.1 Hz, 2H), 3.99 (s, 3H), 3.32 (dd, J=11.6, 5.7 Hz, 2H),2.82 (t, J=5.9 Hz, 2H), 2.44 (t, J=7.2 Hz, 2H), 2.26 - 2.17 (m, 2H), 1.32 (t, J=6.5 Hz, 3H). MS (ESI): [M+H] 399.1818. (2) Synthesis of component A-76: Hyaluronic acid (2g, 340kDa) was dissolved in 100mL 0.01mol / L 2-(N-morpholine)ethanesulfonic acid MES buffer (pH=5.2), stirred until completely dissolved, compound 100 (80mg, 0.2mmol) was weighed and dissolved in 10mL dimethylsulfoxide DMSO, then added to the reaction solution, 4-(4,6-dimethoxytriazin-2-yl)-4-methylmorpholine hydrochloride DMTMM (0.4g, 1.5mmol) was weighed and dissolved in 3mL MES buffer, added to the reaction solution three times (once every hour), and reacted at 35°C for 24 hours. After that, the reaction solution was placed in a dialysis bag (MWCO 7000), dialyzed with deionized water for 2-3 days, and freeze-dried to obtain photosensitive hyaluronic acid derivative A-76 (1.69g). 1 The labeling rate of Compound 100 calculated based on the H-NMR spectrum was about 2.31%.

[0177] <Example 77> Synthesis of Component A-77 [ka] (1) Synthesis of Compound 101: The synthesis is carried out according to the method disclosed in the references Kalbag, SM; Roeske, RWJ Am. Chem. Soc. 1975, 97, 440. 1 H NMR (400mHz, CDCl3): δ =7.71 (s, 1H), 7.22 (s, 1H), 4.55 (s, 2H), 4.63 (q, J=6.9 Hz, 1H), 4.13 (t, J=6.1 Hz, 2H), 3.99 (s, 3H), 3.67 MS (ESI): [M+H] 456.2036. (2) Synthesis of component A-77: Hyaluronic acid (2g, 340kDa) was dissolved in 100mL 0.01mol / L 2-(N-morpholine)ethanesulfonic acid MES buffer (pH=5.2), stirred until completely dissolved, compound 101 (91mg, 0.2mmol) was weighed and dissolved in 10mL dimethylsulfoxide DMSO, then added to the reaction solution, 4-(4,6-dimethoxytriazin-2-yl)-4-methylmorpholine hydrochloride DMTMM (0.4g, 1.5mmol) was weighed and dissolved in 3mL MES buffer, added to the reaction solution three times (once every hour), and reacted at 35°C for 24 hours. After that, the reaction solution was placed in a dialysis bag (MWCO 7000), dialyzed with deionized water for 2-3 days, and freeze-dried to obtain photosensitive hyaluronic acid derivative A-77 (1.82g). 1 The labeling rate of compound 101 calculated based on the H-NMR spectrum was approximately 3.21%.

[0178] <Example 80> Synthesis of Component A-80 [ka] (1) Synthesis of compound 104: Synthesis is performed according to the method disclosed in the references Grazyna Groszek.; Agnieszka Nowak-Krol.; Barbara Filipek. Eur. J. Med. Chem. 2009, 44, 5103. 1 H NMR (400mHz, CDCl3): δ=8.04 (s, 1H), 7.42 (s, 1H), 4.55 (s, 2H), 4.13 (t, J=6.1 Hz, 2H), 3.99 (s, 3H), 3.95 (s, 3H), 3.74 (s, 2H), 3.32 (dd, J=11.6, 5.7 Hz, 2H), 2.82 (t, J=5.9 Hz, 2H), 2.44 (t, J=7.2 Hz, 2H), 2.26 - 2.17 (m, 2H). MS (ESI): [M+H] 399.1832. (2) Synthesis of component A-80: Hyaluronic acid (2g, 340kDa) was dissolved in 100mL 0.01mol / L 2-(N-morpholine)ethanesulfonic acid MES buffer (pH=5.2), stirred until completely dissolved, compound 104 (80mg, 0.2mmol) was weighed and dissolved in 10mL dimethylsulfoxide DMSO, then added to the reaction solution, 4-(4,6-dimethoxytriazin-2-yl)-4-methylmorpholine hydrochloride DMTMM (0.4g, 1.5mmol) was weighed and dissolved in 3mL MES buffer, added to the reaction solution three times (once every hour), and reacted at 35°C for 24 hours. After that, the reaction solution was placed in a dialysis bag (MWCO 7000), dialyzed with deionized water for 2-3 days, and freeze-dried to obtain photosensitive hyaluronic acid derivative A-80 (1.86g). 1 The labeling rate of compound 104 calculated based on the H-NMR spectrum was about 3.32%.

[0179] <Example 81> Synthesis of Component A-81 [ka] (1) Synthesis of compound 105: Synthesis is performed according to the method disclosed in the references Thomas F. Greene.; Shu Wang.; Mary J. Meegan. J. Med. Chem. 2016, 59, 90. 1 H NMR (400mHz, CDCl3): δ=7.95 (s, 1H), 7.12 (s, 1H), 4.55 (s, 2H), 4.13 (t, J=6.1 Hz, 2H), 3.99 (s, 3H), 3.95 (s, 3H), 3.74 (s, 2H), 3.32 (dd, J=11.6, 5.7 Hz, 2H), 2.82 (t, J=5.9 Hz, 2H), 2.44 (t, J=7.2 Hz, 2H), 2.26 - 2.17 (m, 2H). MS (ESI): [M+H] 399.1832. (2) Synthesis of component A-81: Hyaluronic acid (2g, 340kDa) was dissolved in 100mL 0.01mol / L 2-(N-morpholine)ethanesulfonic acid MES buffer (pH=5.2), stirred until completely dissolved, compound 105 (80mg, 0.2mmol) was weighed and dissolved in 10mL dimethylsulfoxide DMSO, then added to the reaction solution, 4-(4,6-dimethoxytriazin-2-yl)-4-methylmorpholine hydrochloride DMTMM (0.4g, 1.5mmol) was weighed and dissolved in 3mL MES buffer, added to the reaction solution three times (once every hour), and reacted at 35°C for 24 hours. After that, the reaction solution was placed in a dialysis bag (MWCO 7000), dialyzed with deionized water for 2-3 days, and freeze-dried to obtain photosensitive hyaluronic acid derivative A-81 (1.89g). 1 The labeling rate of compound 105 calculated based on the H-NMR spectrum was about 3.28%.

[0180] <Example 82> Synthesis of Component A-82 [ka] (1) Synthesis of compound 106: The synthesis is carried out according to the method disclosed in the references Yu-Shan.; Mohane Selvaraj Coumar.; Hsing-Pang Hsieh. J. Med. Chem. 2009, 52, 4941. 1 H NMR (400mHz, CDCl3): δ=7.64 (s, 1H), 7.02 (s, 1H), 4.55 (s, 2H), 4.13 (t, J=6.1 Hz, 2H), 3.99 (s, 3H), 3.95 (s, 3H), 3.74 (s, 2H), 3.32 (dd, J=11.6, 5.7 Hz, 2H), 2.82 (t, J=5.9 Hz, 2H), 2.44 (t, J=7.2 Hz, 2H), 2.26 - 2.17 (m, 2H). MS (ESI): [M+H] 399.1832. (2) Synthesis of component A-82: Hyaluronic acid (2g, 340kDa) was dissolved in 100mL 0.01mol / L 2-(N-morpholine)ethanesulfonic acid MES buffer (pH=5.2), stirred until completely dissolved, compound 106 (80mg, 0.2mmol) was weighed and dissolved in 10mL dimethylsulfoxide DMSO, then added to the reaction solution, 4-(4,6-dimethoxytriazin-2-yl)-4-methylmorpholine hydrochloride DMTMM (0.4g, 1.5mmol) was weighed and dissolved in 3mL MES buffer, added to the reaction solution three times (once every hour), and reacted at 35°C for 24 hours. After that, the reaction solution was placed in a dialysis bag (MWCO 7000), dialyzed with deionized water for 2-3 days, and freeze-dried to obtain photosensitive hyaluronic acid derivative A-82 (1.91g). 1 The labeling rate of compound 106 calculated based on the H-NMR spectrum was about 3.26%.

[0181] <Example 83> Synthesis of Component A-83 [ka] Synthesis of component A-83: Hyaluronic acid (2g, 340kDa) was dissolved in 100mL 0.01mol / L 2-(N-morpholine)ethanesulfonic acid MES buffer solution (pH=5.2), stirred until completely dissolved, weighed nNB mixture (compound 92 / compound 95, 60mg, mass ratio 1:1) and dissolved in 10mL dimethylsulfoxide DMSO, then added to the reaction solution, weighed 4-(4,6-dimethoxytriazin-2-yl)-4-methylmorpholine hydrochloride DMTMM (0.4g, 1.5mmol) was dissolved in 3mL MES buffer solution, added to the reaction solution in three portions (once every hour), and reacted at 35°C for 24 hours. Thereafter, the reaction solution was placed in a dialysis bag (MWCO 7000), dialyzed against deionized water for 2-3 days, and freeze-dried to obtain photosensitive hyaluronic acid derivative A-83 (1.89 g). 1 The labeling rate of the nNB mixture (Compound 92 / Compound 95) calculated based on the H-NMR spectrum was approximately 3.42%.

[0182] <Example 84> Synthesis of Component A-84 [ka] Synthesis of component A-84: Carboxymethyl cellulose (2 g, 90 kDa) was dissolved in 100 mL 0.01 mol / L 2-(N-morpholine)ethanesulfonic acid MES buffer (pH = 5.2), stirred until completely dissolved, compound 95 (80 mg, 0.2 mmol) was weighed and dissolved in 10 mL dimethyl sulfoxide DMSO, and then added to the reaction solution, 4-(4,6-dimethoxytriazin-2-yl)-4-methylmorpholine hydrochloride DMTMM (0.4 g, 1.5 mmol) was weighed and dissolved in 3 mL MES buffer, and added to the reaction solution three times (once every hour), and reacted at 35 ° C for 24 hours. Then, the reaction solution was placed in a dialysis bag (MWCO 7000), dialyzed with deionized water for 2-3 days, and freeze-dried to obtain photosensitive carboxymethyl cellulose derivative A-84 (1.72 g). 1The labeling rate of compound 95 molecules calculated based on the H-NMR spectrum was approximately 2.21%.

[0183] <Example 85> Synthesis of Component A-85 [ka] (1) Synthesis of Compound 107: Compound 107 was prepared by conventional chemical means according to the method of Example 71. 1 H NMR (400mHz, CDCl3): δ=7.71 (s, 1H), 7.22 (s, 1H), 4.55 (s, 2H), 4.13 (t, J=6.1 Hz, 2H), 3.99 (s, 3H), 3.95 (s, 3H), 3.74 (s, 2H), 2.44 (t, J=7.2 Hz, 2H), 2.26 - 2.17 (m, 2H). MS (ESI): [M+H] 357.1342. (2) Synthesis of component A-85: 1 g of chitosan was added to 75 mL of isopropanol to form a suspension of chitosan, and then compound 107 (0.2 g, 0.56 mmol), EDC-HCl (0.76 g, 3.96 mmol) and NHS (0.46 g, 4.0 mmol) were added to the solution in order and reacted at room temperature for 48 hours while stirring. After the reaction was completed, the mixture was dialyzed with a dilute hydrochloric acid solution (pH = 3.5) containing sodium chloride for one day, and then further dialyzed with pure water for one day and freeze-dried to obtain photosensitive chitosan derivative A-85 (0.82 g). The degree of modification of compound 107 calculated based on its 1H-NMR spectrum was about 11.3%.

[0184] <Example 86> Synthesis of Component A-86 [ka] (1) Synthesis of Compound 108: Compound 108 was prepared by conventional chemical means according to the method of Example 71. 1H NMR (400mHz, CDCl3): δ=7.71 (s, 1H), 7.22 (s, 1H), 4.55 (s, 2H), 4.13 (t, J=6.1 Hz, 2H), 3.99 (s, 3H), 3.95 (s, 3H), 3.74 (s, 2H), 3.04 (t, J=7.2 Hz, 2H). MS (ESI): [M+H] 377.0346. (2) Synthesis of component A-86: PEG-4OH (1g, 0.05mmol) was dissolved in anhydrous acetonitrile, K2CO3 (55.3mg, 0.4mmol) was added, and the mixture was stirred for 30 minutes. Compound 108 (0.15g, 0.4mmol) was then added and the mixture was allowed to react at room temperature for 24 hours. After the reaction was completed, most of the solvent was removed, the mixture was reprecipitated in diethyl ether, washed several times, filtered by suction, and dried to obtain photosensitive polyethylene glycol derivative A-86 (0.93g). 1 The degree of modification of compound 108 was calculated to be about 95% based on the H-NMR spectrum.

[0185] <Example 87> Synthesis of Component A-87 [ka] (1) Synthesis of Compound 109: Compound 108 (0.5 g, 1.29 mmol) and ethylene glycol (0.24 g, 3.87 mmol) were dissolved in anhydrous acetonitrile, K2CO3 (0.5 g, 3.87 mmol) was added as a base, and the mixture was allowed to react overnight under reflux. After the reaction was completed, the solvent was removed by rotary evaporation under reduced pressure, and compound 109 (0.34 g, 72%) was obtained by column purification. 1H NMR (400mHz, CDCl3): δ=7.71 (s, 1H), 7.22 (s, 1H), 4.55 (s, 2H), 4.13 (t, J=6.1 Hz, 2H), 3.99 (s, 3H), 3.95 (s, 3H), 3.79 (t, J=6.1 Hz, 2H), 3.74 (s, 2H), 3.70 (t, J=7.2 Hz, 2H), 3.56 (t, J=7.2 Hz, 2H). MS (ESI): [M+H] 359.1462. (2) Synthesis of Compound 110: Compound 109 (0.64 g, 1.72 mmol) and triethylamine (0.34 g, 3.44 mmol) were dissolved in dry dichloromethane, and methacryloyl chloride (0.27 g, 2.58 mmol) was slowly added dropwise to the solution under ice bath conditions. After the addition was completed, the mixture was allowed to react overnight at room temperature. After the reaction was completed, the solvent was removed by rotary evaporation under reduced pressure, and compound 110 (0.49 g, 65%) was obtained by column purification. 1 H NMR (400mHz, CDCl3): δ=7.71 (s, 1H), 7.22 (s, 1H), 6.25 (s, 1H), 5.68 (s, 1H), 4.55 (s, 2H), 4.13 (t, J=6.1 Hz, 2H), 3.99 (s, 3H), 3.95 (s, 3H), 3.79 (t, J=6.1 Hz, 2H), 3.74 (s, 2H), 3.70 (t, J=7.2 Hz, 2H), 3.56 (t, J=7.2 Hz, 2H), 1.87 (s, 3H). MS (ESI): [M+H] 427.1725. (3) Synthesis of component A-87: Compound 110 (0.28 g, 0.63 mmol), comonomer PEG-MA (0.882 g, 2.52 mmol) and initiator azobisisobutyronitrile (11 mg) were weighed and added to a Schreck flask, dissolved by adding anhydrous THF, and treated by multiple cycles of freezing and vacuuming. The reaction system was reacted for 24 hours at 75°C. After the reaction was completed, the reaction solution was put into cold diethyl ether and purified by multiple reprecipitations to obtain photosensitive copolymer derivative A-87 (0.85 g). 1The content of compound 110 in the copolymer was calculated to be about 14.6% based on the H-NMR spectrum. The molecular weight of the synthetic polymer measured by GPC was about 25 kDa. As a result of calculation based on the blending ratio, n was 12, x was 10, and y was 40.

[0186] <Example 88> Synthesis of Component A-88 [ka] (1) Synthesis of Compound 111: Vanillin (25 g, 165 mmol) and potassium carbonate (11.4 g, 83 mmol) were dissolved in 200 mL of acetone, and benzyl bromide (21.2 g, 181 mmol) was added dropwise to the solution, and the mixture was allowed to react for 8 hours under reflux at 90°C. After the reaction was completed, the reaction system was cooled to room temperature, and then the acetone was removed by distillation under reduced pressure. 100 mL of water was added, and the mixture was extracted three times with ethyl acetate. The organic phases were combined, dried with anhydrous sodium sulfate, and the organic solvent was removed by rotary drying to obtain a colorless liquid. The mixture was then recrystallized with 100 mL of ethanol to obtain Compound 111 (36.2 g, 91%), which was a white needle-shaped product. 1 H NMR (400mHz, CDCl3): δ=9.83 (s, 1H), 7.39 (ddd, J=24.2, 20.7, 7.4 Hz, 7H), 6.98 (d, J=8.2 Hz, 1H), 5.24 (s, 2H), 3.94 (d, J=0.9 Hz, 3H). MS (ESI): [M+Na] 265.0824. (2) Synthesis of Compound 112: Compound 111 (10 g, 41.3 mmol) was dissolved in 50 mL of acetic anhydride, and 50 mL of nitric acid (65%) was added dropwise under ice bath conditions. After the addition, the ice bath was removed and the reaction was allowed to proceed at room temperature for 30 minutes. After the reaction was completed, the reaction system was slowly poured into 600 mL of ice water to precipitate a yellow solid. The yellow solid was obtained by filtration under reduced pressure, and then recrystallized from ethanol to obtain a yellow needle-like product, Compound 112 (9.72 g, 82%). 1H NMR (400mHz, CDCl3): δ=10.42 (s, 1H), 7.67 (s, 1H), 7.43 - 7.39 (m, 3H), 7.37 (d, J=7.0 Hz, 1H), 5.26 (s, 2H), 4.01 (s, 3H). MS (ESI): [M+Na] 310.0689. (3) Synthesis of compound 113: Compound 112 (9 g, 31.3 mmol) was dissolved in 200 mL of methanol, and sodium borohydride (2.37 g, 62.6 mmol) was slowly added under ice bath conditions. The ice bath was then removed and the mixture was allowed to react for 30 minutes at room temperature. After the reaction was completed, 2 mol / L of hydrochloric acid was added to adjust the pH to 7. Then, the methanol was removed by distillation under reduced pressure, 100 mL of water was added, and the mixture was extracted three times with ethyl acetate. The organic phases were combined, dried with anhydrous sodium sulfate, and the solvent was removed by rotary drying to obtain a yellow solid product. The yellow solid product was recrystallized with ethanol to obtain compound 113 (9.06 g, 92%). 1 H NMR (400mHz, CDCl3): δ=7.77 (s, 1H), 7.49-7.42 (m, 2H), 7.40 (dd, J=8.1, 6.4 Hz, 3H), 7.18 (s, 1H), 5.20 (s, 2H), 4.95 (s, 2H), 4.00 (s, 3H). MS (ESI): [M+Na] 312.0834. (4) Synthesis of compound 114: Compound 113 (3 g, 10.4 mmol) was dissolved in 100 mL dry tetrahydrofuran, ventilated three times, and added triphenylphosphine (4.08 g, 15.6 mmol) and carbon tetrabromide (5.16 g, 15.6 mmol) simultaneously under ice bath conditions, then removed the ice bath and reacted at room temperature for 2 hours. After the reaction was completed, 6 mL of water was added to stop the reaction system, and then tetrahydrofuran was removed by rotary distillation under reduced pressure, extracted twice with saturated saline and ethyl acetate, and further extracted three times with water and ethyl acetate. The organic phases were combined, dried with anhydrous sodium sulfate, and the solvent was removed by rotary evaporation under reduced pressure. Compound 114 (3.09 g, 85%) was obtained as a yellow powder by separation by dry column chromatography (PE: CH2Cl2 = 4:1). 1H NMR (400mHz, CDCl3): δ=7.71 (s, 1H), 7.46-7.41 (m, 2H), 7.40-7.30 (m, 3H), 6.93 (s, 1H), 5.17-5.13 (m, 2H), 4.8-4.79 (m, 2H), 3.95 (s, 3H), 1.42(s, 9H). MS (ESI): [M+Na] 374.0003. (5) Synthesis of Compound 115: Compound 114 (3g, 8.5mmol) was dissolved in 120mL acetone, ventilated three times, and L-cysteine ​​methyl ester hydrochloride (2.9g, 17mmol) and sodium hydroxide (0.85g, 21.25mmol) were added under the protection of argon, ventilated three more times, and reacted at room temperature for 2 hours. After the reaction was completed, 4mol / L hydrochloric acid was added to the reaction system to adjust the pH to 7, acetone was removed by rotary distillation under reduced pressure, and the mixture was extracted three times with saturated saline and ethyl acetate, and then extracted three times with water and ethyl acetate. The organic phases were combined and dried over anhydrous sodium sulfate. Compound 115 (2.71g, 78%) was obtained as a yellow solid by separation using dry column chromatography (CH2Cl2:CH3OH=100:3). 1 H NMR (400mHz, CDCl3): δ=7.71 (s, 1H), 7.45 (d, J=7.0 Hz, 2H), 7.39 (t, J=7.2 Hz, 3H), 6.95 (s, 1H), 5.18 (s, 2H), 4.13 (q, J=13.6 Hz, MS (ESI): [M+H] 407.1277. (6) Synthesis of Compound 116: Tetraethylene glycol (22 g, 113.2 mmol) was added to dry tetrahydrofuran, metallic sodium (40 mg, 1.74 mmol) was added to generate bubbles, and after sodium was completely dissolved, tert-butyl acrylate (8 g, 62.4 mmol) was added and reacted at room temperature for 20 hours. After the reaction was completed, the reaction system was adjusted to pH=7 with 1 mol / L hydrochloric acid, tetrahydrofuran was removed by rotary distillation under reduced pressure, extracted three times with saturated saline and ethyl acetate, and further extracted three times with water and ethyl acetate. The organic phases were combined, dried over anhydrous sodium sulfate, and the solvent was removed by rotary evaporation under reduced pressure to obtain Compound 116 (16.0 g, 80%), which was a colorless oily liquid, without further purification. 1 H NMR (400mHz, CDCl3): δ=3.78-3.69 (m, 4H), 3.69 - 3.54 (m, 14H), 2.52 (dd, J=4.3, 2.1 Hz, 2H), 1.45 (s, 9H). MS (ESI): [M+Na] 345.1872. (7) Synthesis of Compound 117: Compound 116 (10 g, 31.2 mmol) was dissolved in dry dichloromethane, and dry triethylamine (5.2 mmL, 37.4 mmol) was added. Then, p-toluenesulfonyl chloride (8.9 g, 46.8 mmol) was added to 40 mL of dry dichloromethane, and the mixture was added dropwise to the reaction system under ice bath conditions. After the addition, the ice bath was removed and the mixture was reacted at room temperature for 6 hours. After the reaction was completed, 200 mL of water was added to the reaction system as it was, and the mixture was extracted three times with dichloromethane. The organic layers were combined, dried with anhydrous sodium sulfate, the solvent was removed by rotary evaporation, and the mixture was separated by column chromatography (CH2Cl2:CH3OH=50:1) to obtain Compound 117 (12.6 g, 85%), which is a pale yellow oily liquid. 1H NMR (400mHz, CDCl3): δ=7.79-7.74 (m, 2H), 7.32 (d, J=8.5 Hz, 2H), 4.21-3.90 (m, 2H), 3.66 (dd, J=5.7, 2.8 Hz, 4H), 3.62-3.35 (m, MS (ESI): [M+Na] 499.1964. (8) Synthesis of Compound 118: Compound 117 (10 g, 21.0 mmol) and lithium bromide (4.8 g, 31.5 mmol) were dissolved in 30 mL of N,N-dimethylformamide, heated to 80° C., and reacted for 1 hour. After the reaction was completed, N,N-dimethylformamide was removed by rotary distillation under reduced pressure, and the mixture was extracted three times with water and dichloromethane. The organic layers were combined, dried over anhydrous sodium sulfate, and the solvent was removed by rotary evaporation under reduced pressure. The mixture was separated by column chromatography (CHCl) to obtain Compound 118 (7.3 g, 90%) as a pale yellow liquid. 1 H NMR (400mHz, CDCl3): δ=3.72 (t, J=6.3 Hz, 2H), 3.62 (t, J=6.6 Hz, 2H), 3.58 (dd, J=2.6, 1.5 Hz, 8H), 3.54 (d, J=2.2 Hz, 4H), 3.39 (t, MS (ESI): [M+Na] 409.1005. (9) Synthesis of Compound 119: Compound 118 (5 g, 13.0 mmol) was added to 30 mL of dry dichloromethane, and 10 mL of trifluoroacetic acid was added and reacted at room temperature for 30 minutes. After the reaction was completed, the solvent was removed by rotary evaporation under reduced pressure. The product was then dissolved in dichloromethane and ethyl acetate, respectively, and the solvent was removed by rotary evaporation under reduced pressure to completely remove trifluoroacetic acid. Compound 119 (3.9 g, 92%) was obtained as a yellow oily liquid without further purification. 1H NMR (400mHz, CDCl3): δ=3.72 (t, J=6.3 Hz, 2H), 3.67 (t, J=6.3 Hz, 2H), 3.58 (dd, J=4.1, 1.7 Hz, 4H), 3.57 (s, 4H), 3.55 (s, 4H), 3.39 (t, J=6.3 Hz, 2H), 2.54 (t, J=6.3 Hz, 2H). MS (ESI): [M+Na] 353.0414. (10) Synthesis of compound 120: Compound 115 (2.0 g, 4.9 mmol) and compound 119 (2.0 g, 5.9 mmol) were dissolved in 40 mL of dry dichloromethane, and hexafluorophosphate benzotriazol-1-yl-oxypyrrole alkyl group (5.1 g, 9.8 mmol) and dry triethylamine (1.4 mL, 9.8 mmol) were added, and the mixture was reacted at room temperature for 1 hour. After the reaction was completed, 100 mL of water was added to the reaction system, and the mixture was extracted three times with dichloromethane and water. The organic phases were combined, dried over anhydrous sodium sulfate, and the solvent was removed by rotary evaporation under reduced pressure. The mixture was separated by dry column chromatography (CH2Cl2:CH3OH=100:3) to obtain compound 120 (2.2 g, 62%) as a yellow liquid. 1 H NMR (400mHz, CDCl3): δ= 7.71 (s, 1H), 7.45 (d, J=7.0 Hz, 2H), 7.39 (t, J=7.2 Hz, 3H), 6.95 (s, 1H), 5.18 (s, 2H), 4.42 (m, 1H),4.13 (q, J=13.6 Hz, 2H), 3.98 (s, 3H), 3.73 (s, 3H), 3.68 - 3.63 (m, 2H), 3.62 - 3.55 (m, 4H), 3.58-3.53 (m, 12H), 3.37 (t, J=6.3 Hz, 2H),2.43 (t, J=5.8 Hz, 2H).MS (ESI): [M+Na] 741.1529. (11) Synthesis of Compound 121: Compound 120 (2 g, 2.8 mmol) was dissolved in 20 mL of trifluoroacetic acid and reacted at 45° C. for 8 hours. After the reaction was completed, trifluoroacetic acid was removed by rotary distillation under reduced pressure, and the mixture was extracted three times with dichloromethane and water. The organic layers were combined, dried over anhydrous sodium sulfate, and the solvent was removed by rotary evaporation under reduced pressure. Compound 121 (1.4 g, 82%) was obtained as a yellow liquid by separation using column chromatography (CH2Cl2:CH3OH=25:1). 1 H NMR (400mHz, CDCl3): δ=7.60 (s, 1H), 6.79 (s, 1H), 4.73-4.66 (m, 1H), 3.99 (d, J=12.9 Hz, 2H), 3.97 (s, 3H),3.73 (s, 3H), 3.70 (d, MS (ESI): [M+Na] 651.1026. (12) Synthesis of compound 122: Compound 121 (0.5 g, 0.8 mmol) was dissolved in 400 mL of acetone, potassium carbonate (0.2 g, 1.6 mmol) was added, and the mixture was allowed to react for 4 hours under reflux at 75°C. After the reaction was completed, insoluble matter was removed by filtration under reduced pressure, and then the acetone was removed by rotary drying. The mixture was separated by column chromatography (CH2Cl2:CH3OH=25:1) to obtain compound 122 (0.27 g, 61%) as a yellow solid. 1 H NMR (400mHz, DMSO): δ= 7.71 (s, 1H), 7.17 (s, 1H),4.76 (s, 2H), 4.42 (m, 1H),3.97 (s, 3H), 3.73 (s, 3H), 3.72 (d, J=6.3 Hz, 2H), 3.62 - 3.55 (m, 4H), 3.52-3.39 (m, 14H), 2.49 - 2.35 (m, 2H). MS (ESI): [M+Na] 569.1782. (13) Synthesis of compound 123: Compound 122 (0.2 g, 3.7 mmol) was dissolved in 20 mL of anhydrous ethylenediamine and reacted at room temperature for 6 hours. After the reaction was completed, ethylenediamine was removed by rotary distillation under reduced pressure, and the mixture was separated by dry column chromatography (CH2Cl2:CH3OH:triethylamine=100:8:0.5) to obtain compound 123 (0.19 g, 89%) as a yellow powder. 1 H NMR (400mHz, DMSO): δ= 7.71 (s, 1H), 7.17 (s, 1H),4.76 (s, 2H), 4.42 (m, 1H),3.97 (s, 3H),3.72 (d,J=6.3 Hz, 2H), 3.62 - 3.55 (m, MS (ESI): [M+Na] 597.2211. [ka] (14) Synthesis of component A-88: ​​Hyaluronic acid (2g, 340kDa) was dissolved in 100mL 0.01mol / L 2-(N-morpholine)ethanesulfonic acid MES buffer (pH=5.2), stirred until completely dissolved, compound 123 (115mg, 0.2mmol) was weighed and dissolved in 10mL dimethylsulfoxide DMSO, then added to the reaction solution, 4-(4,6-dimethoxytriazin-2-yl)-4-methylmorpholine hydrochloride DMTMM (0.4g, 1.5mmol) was weighed and dissolved in 3mL MES buffer, added to the reaction solution three times (once every hour), and reacted at 35°C for 24 hours. After that, the reaction solution was placed in a dialysis bag (MWCO 7000), dialyzed with deionized water for 2-3 days, and freeze-dried to obtain photosensitive hyaluronic acid derivative A-88 (1.87g). 1 The labeling rate of compound 123 molecules calculated based on the H-NMR spectrum was approximately 3.49%.

[0187] <Example 89> Synthesis of Component A-89 [ka] (1) Synthesis of Compound 124: Compound 124 was prepared by conventional chemical means according to the method of Example 88. 1 H NMR (400mHz, DMSO): δ= 7.71 (s, 1H), 7.17 (s, 1H),4.96 (s, 2H), 4.42 (m, 1H),3.97 (s, 3H),3.72 (d,J=6.3 Hz, 2H), 3.62 - 3.55 (m, MS (ESI): [M+Na] 559.2642. (2) Synthesis of component A-89: Hyaluronic acid (2g, 340kDa) was dissolved in 100mL 0.01mol / L 2-(N-morpholine)ethanesulfonic acid MES buffer (pH=5.2), stirred until completely dissolved, compound 124 (111mg, 0.2mmol) was weighed and dissolved in 10mL dimethylsulfoxide DMSO, then added to the reaction solution, 4-(4,6-dimethoxytriazin-2-yl)-4-methylmorpholine hydrochloride DMTMM (0.4g, 1.5mmol) was weighed and dissolved in 3mL MES buffer, added to the reaction solution three times (once every hour), and reacted at 35°C for 24 hours. After that, the reaction solution was placed in a dialysis bag (MWCO 7000), dialyzed with deionized water for 2-3 days, and freeze-dried to obtain photosensitive hyaluronic acid derivative A-89 (1.82g). 1 The labeling rate of compound 124 calculated based on the H-NMR spectrum was approximately 3.15%.

[0188] <Example 90> Synthesis of Component A-90 [ka] (1) Synthesis of Compound 125: Compound 125 was prepared by conventional chemical means according to the method of Example 88. 1H NMR (400mHz, DMSO): δ= 7.71 (s, 1H), 7.17 (s, 1H),4.26 (s, 2H), 4.42 (m, 1H),3.97 (s, 3H),3.42 (d,J=6.3 Hz, 2H), 3.62 - 3.55 (m, MS (ESI): [M+Na] 558.2725. (2) Synthesis of component A-90: Hyaluronic acid (2g, 340kDa) was dissolved in 100mL 0.01mol / L 2-(N-morpholine)ethanesulfonic acid MES buffer (pH=5.2), stirred until completely dissolved, compound 125 (111mg, 0.2mmol) was weighed and dissolved in 10mL dimethylsulfoxide DMSO, then added to the reaction solution, 4-(4,6-dimethoxytriazin-2-yl)-4-methylmorpholine hydrochloride DMTMM (0.4g, 1.5mmol) was weighed and dissolved in 3mL MES buffer, added to the reaction solution three times (once every hour), and reacted at 35°C for 24 hours. After that, the reaction solution was placed in a dialysis bag (MWCO 7000), dialyzed with deionized water for 2-3 days, and freeze-dried to obtain photosensitive hyaluronic acid derivative A-90 (1.87g). 1 The labeling rate of compound 125 calculated based on the H-NMR spectrum was approximately 3.27%.

[0189] <Example 91> Synthesis of Component A-91 [ka] (1) Synthesis of Compound 126: Compound 126 was prepared by conventional chemical means according to the method of Example 88. 1H NMR (400mHz, DMSO): δ= 7.71 (s, 1H), 7.17 (s, 1H),5.16 (m, 1H), 4.42 (m, 1H),3.97 (s, 3H),3.72 (d,J=6.3 Hz, 2H), 3.62 - 3.55 (m, MS (ESI): [M+Na] 589.2517. (2) Synthesis of component A-91: Hyaluronic acid (2g, 340kDa) was dissolved in 100mL 0.01mol / L 2-(N-morpholine)ethanesulfonic acid MES buffer (pH=5.2), stirred until completely dissolved, compound 126 (118mg, 0.2mmol) was weighed and dissolved in 10mL dimethylsulfoxide DMSO, then added to the reaction solution, 4-(4,6-dimethoxytriazin-2-yl)-4-methylmorpholine hydrochloride DMTMM (0.4g, 1.5mmol) was weighed and dissolved in 3mL MES buffer, added to the reaction solution three times (once every hour), and reacted at 35°C for 24 hours. After that, the reaction solution was placed in a dialysis bag (MWCO 7000), dialyzed with deionized water for 2-3 days, and freeze-dried to obtain photosensitive hyaluronic acid derivative A-91 (1.73g). 1 The labeling rate of compound 126 calculated based on the H-NMR spectrum was approximately 3.14%.

[0190] <Example 93> Synthesis of Component A-93 [ka] (1) Synthesis of Compound 128: Compound 128 was prepared by conventional chemical means according to the method of Example 88. 1H NMR (400mHz, DMSO): δ= 7.71 (s, 1H), 7.17 (s, 1H),5.82 (m, 1H),4.76 (s, 2H), 3.97 (s, 3H), 3.62 - 3.55 (m, 2H), 3.52-3.39 (m, MS (ESI): [M+Na] 589.2143. (2) Synthesis of component A-93: Hyaluronic acid (2g, 340kDa) was dissolved in 100mL 0.01mol / L 2-(N-morpholine)ethanesulfonic acid MES buffer (pH=5.2), stirred until completely dissolved, compound 128 (118mg, 0.2mmol) was weighed and dissolved in 10mL dimethylsulfoxide DMSO, then added to the reaction solution, 4-(4,6-dimethoxytriazin-2-yl)-4-methylmorpholine hydrochloride DMTMM (0.4g, 1.5mmol) was weighed and dissolved in 3mL MES buffer, added to the reaction solution three times (once every hour), and reacted at 35°C for 24 hours. After that, the reaction solution was placed in a dialysis bag (MWCO 7000), dialyzed with deionized water for 2-3 days, and freeze-dried to obtain photosensitive hyaluronic acid derivative A-93 (1.73g). 1 The labeling rate of compound 128 calculated based on the H-NMR spectrum was approximately 3.15%.

[0191] <Example 94> Synthesis of Component A-94 [ka] (1) Synthesis of Compound 129: Compound 129 was prepared by conventional chemical means according to the method of Example 88. 1H NMR (400mHz, DMSO): δ= 7.71 (s, 1H), 7.17 (s, 1H),4.76 (s, 2H), 4.13 (t, J=7.2 Hz, 2H), 3.62 - 3.55 (m, 2H), 3.52-3.39 (m, 16H), 2.86 (d, J=7.6 Hz, 2H), 2.76 (d, J=7.6 Hz, 2H), 2.49 - 2.35 (m, 2H),2.44 (t, J=7.2 Hz, 2H), 2.26 - 2.17 (m, 2H). MS (ESI): [M+Na] 575.2332. (2) Synthesis of component A-94: Hyaluronic acid (2g, 340kDa) was dissolved in 100mL 0.01mol / L 2-(N-morpholine)ethanesulfonic acid MES buffer (pH=5.2), stirred until completely dissolved, compound 129 (115mg, 0.2mmol) was weighed and dissolved in 10mL dimethylsulfoxide DMSO, then added to the reaction solution, 4-(4,6-dimethoxytriazin-2-yl)-4-methylmorpholine hydrochloride DMTMM (0.4g, 1.5mmol) was weighed and dissolved in 3mL MES buffer, added to the reaction solution three times (once every hour), and reacted at 35°C for 24 hours. After that, the reaction solution was placed in a dialysis bag (MWCO 7000), dialyzed with deionized water for 2-3 days, and freeze-dried to obtain photosensitive hyaluronic acid derivative A-94 (1.84g). 1 The labeling rate of compound 129 calculated based on the H-NMR spectrum was approximately 2.47%.

[0192] <Example 95> Synthesis of Component A-95 [ka] (1) Synthesis of Compound 130: Compound 130 was prepared by conventional chemical means according to the method of Example 88. 1H NMR (400mHz, DMSO): δ= 7.71 (s, 1H), 7.17 (s, 1H),4.76 (s, 2H), 4.13 (t, J=7.2 Hz, 2H), 3.62 - 3.55 (m, 2H), 3.52-3.39 (m, 16H), 2.86 (d, J=7.6 Hz, 2H), 2.76 (d, J=7.6 Hz, 2H), 2.69 - 2.55 (m, 2H),2.44 (t, J=7.2 Hz, 2H), 2.26 - 2.17 (m, 2H). MS (ESI): [M+Na] 576.2242. (2) Synthesis of component A-95: Hyaluronic acid (2g, 340kDa) was dissolved in 100mL 0.01mol / L 2-(N-morpholine)ethanesulfonic acid MES buffer (pH=5.2), stirred until completely dissolved, compound 130 (115mg, 0.2mmol) was weighed and dissolved in 10mL dimethylsulfoxide DMSO, then added to the reaction solution, 4-(4,6-dimethoxytriazin-2-yl)-4-methylmorpholine hydrochloride DMTMM (0.4g, 1.5mmol) was weighed and dissolved in 3mL MES buffer, added to the reaction solution three times (once every hour), and reacted at 35°C for 24 hours. After that, the reaction solution was placed in a dialysis bag (MWCO 7000), dialyzed with deionized water for 2-3 days, and freeze-dried to obtain photosensitive hyaluronic acid derivative A-95 (1.75g). 1 The labeling rate of compound 130 calculated based on the H-NMR spectrum was approximately 3.07%.

[0193] <Example 98> Synthesis of Component A-98 [ka] (1) Synthesis of Compound 133: Compound 133 was prepared by conventional chemical means according to the method of Example 88. 1H NMR (400mHz, DMSO): δ= 8.11 (m, 1H), 7.27 (m, 1H),4.76 (s, 2H), 4.42 (m, 1H),3.97 (s, 3H),3.72 (d,J=6.3 Hz, 2H), 3.62 - 3.55 (m, MS (ESI): [M+Na] 531.2143. (2) Synthesis of component A-98: Hyaluronic acid (2g, 340kDa) was dissolved in 100mL 0.01mol / L 2-(N-morpholine)ethanesulfonic acid MES buffer (pH=5.2), stirred until completely dissolved, compound 133 (106mg, 0.2mmol) was weighed and dissolved in 10mL dimethylsulfoxide DMSO, then added to the reaction solution, 4-(4,6-dimethoxytriazin-2-yl)-4-methylmorpholine hydrochloride DMTMM (0.4g, 1.5mmol) was weighed and dissolved in 3mL MES buffer, added to the reaction solution three times (once every hour), and reacted at 35°C for 24 hours. After that, the reaction solution was placed in a dialysis bag (MWCO 7000), dialyzed with deionized water for 2-3 days, and freeze-dried to obtain photosensitive hyaluronic acid derivative A-98 (1.78g). 1 The labeling rate of compound 133 calculated based on the H-NMR spectrum was approximately 3.31%.

[0194] <Example 99> Synthesis of Component A-99 [ka] (1) Synthesis of Compound 134: Compound 134 was prepared by conventional chemical means according to the method of Example 88. 1H NMR (400mHz, DMSO): δ= 7.71 (s, 1H), 7.17 (s, 1H),4.76 (s, 2H), 4.42 (m, 1H),3.97 (s, 3H),3.72 (d,J=6.3 Hz, 2H), 3.62 - 3.55 (m, MS (ESI): [M+Na] 575.2342. (2) Synthesis of component A-99: Hyaluronic acid (2g, 340kDa) was dissolved in 100mL 0.01mol / L 2-(N-morpholine)ethanesulfonic acid MES buffer (pH=5.2), stirred until completely dissolved, compound 134 (115mg, 0.2mmol) was weighed and dissolved in 10mL dimethylsulfoxide DMSO, then added to the reaction solution, 4-(4,6-dimethoxytriazin-2-yl)-4-methylmorpholine hydrochloride DMTMM (0.4g, 1.5mmol) was weighed and dissolved in 3mL MES buffer, added to the reaction solution three times (once every hour), and reacted at 35°C for 24 hours. After that, the reaction solution was placed in a dialysis bag (MWCO 7000), dialyzed with deionized water for 2-3 days, and freeze-dried to obtain photosensitive hyaluronic acid derivative A-99 (1.84g). 1 The labeling rate of compound 134 calculated based on the H-NMR spectrum was approximately 3.06%.

[0195] Example 100: Synthesis of Component A-100 [ka] (1) Synthesis of Compound 135: Compound 135 was prepared by conventional chemical means according to the method of Example 88. 1H NMR (400mHz, DMSO): δ= 7.54 (m, 1H), 7.03 (m, 1H),4.76 (s, 2H), 4.42 (m, 1H),3.97 (s, 3H),3.72 (d,J=6.3 Hz, 2H), 3.62 - 3.55 (m, MS (ESI): [M+Na] 619.2652. (2) Synthesis of component A-100: Hyaluronic acid (2g, 340kDa) was dissolved in 100mL 0.01mol / L 2-(N-morpholine)ethanesulfonic acid MES buffer (pH=5.2), stirred until completely dissolved, compound 135 (124mg, 0.2mmol) was weighed and dissolved in 10mL dimethylsulfoxide DMSO, then added to the reaction solution, 4-(4,6-dimethoxytriazin-2-yl)-4-methylmorpholine hydrochloride DMTMM (0.4g, 1.5mmol) was weighed and dissolved in 3mL MES buffer, added to the reaction solution three times (once every hour), and reacted at 35°C for 24 hours. After that, the reaction solution was placed in a dialysis bag (MWCO 7000), dialyzed with deionized water for 2-3 days, and freeze-dried to obtain photosensitive hyaluronic acid derivative A-100 (1.84g). 1 The labeling rate of compound 135 calculated based on the H-NMR spectrum was approximately 3.16%.

[0196] <Example 101> Synthesis of Component A-101 [ka] (1) Synthesis of Compound 136: Compound 136 was prepared by conventional chemical means according to the method of Example 88. 1H NMR (400mHz, DMSO): δ= 7.71 (s, 1H), 7.17 (s, 1H),4.76 (s, 2H), 4.42 (m, 1H),4.13 (t, J=7.2 Hz, 2H), 3.73 (s, 3H), 3.72 (d,J=6.3 Hz, 2H), 3.62 - 3.55 (m, 2H), 3.52-3.39 (m, 16H), 2.86 (d, J=7.6 Hz, 2H), 2.76 (d, J=7.6 Hz, 2H), 2.49 - 2.35 (m, 2H),2.44 (t, J=7.2 Hz, 2H), 2.26 - 2.17 (m, 2H). MS (ESI): [M+Na] 661.2745. (2) Synthesis of component A-101: Hyaluronic acid (2g, 340kDa) was dissolved in 100mL 0.01mol / L 2-(N-morpholine)ethanesulfonic acid MES buffer (pH=5.2), stirred until completely dissolved, compound 136 (132mg, 0.2mmol) was weighed and dissolved in 10mL dimethylsulfoxide DMSO, then added to the reaction solution, 4-(4,6-dimethoxytriazin-2-yl)-4-methylmorpholine hydrochloride DMTMM (0.4g, 1.5mmol) was weighed and dissolved in 3mL MES buffer, added to the reaction solution three times (once every hour), and reacted at 35°C for 24 hours. After that, the reaction solution was placed in a dialysis bag (MWCO 7000), dialyzed with deionized water for 2-3 days, and freeze-dried to obtain photosensitive hyaluronic acid derivative A-101 (1.77g). 1 The labeling rate of compound 136 calculated based on the H-NMR spectrum was approximately 3.21%.

[0197] <Example 102> Synthesis of Component A-102 [ka] Synthesis of component A-102: Hyaluronic acid (2g, 340kDa) was dissolved in 100mL 0.01mol / L 2-(N-morpholine)ethanesulfonic acid MES buffer solution (pH=5.2), stirred until completely dissolved, weighed out cNB mixture (compound 123 / compound 136, 60mg, mass ratio 1:1) and dissolved in 10mL dimethylsulfoxide DMSO, then added to the reaction solution, weighed out 4-(4,6-dimethoxytriazin-2-yl)-4-methylmorpholine hydrochloride DMTMM (0.4g, 1.5mmol) was dissolved in 3mL MES buffer solution, and added to the reaction solution in three portions (once every hour), and reacted at 35°C for 24 hours. Thereafter, the reaction solution was placed in a dialysis bag (MWCO 7000), dialyzed against deionized water for 2-3 days, and freeze-dried to obtain photosensitive hyaluronic acid derivative A-102 (1.89 g). 1 The labeling rate of the cNB mixture (compound 123 / compound 136) calculated based on the H-NMR spectrum was approximately 3.52%.

[0198] <Example 103> Synthesis of Component A-103 [ka] Synthesis of component A-103: Carboxymethyl cellulose (2 g, 90 kDa) was dissolved in 100 mL 0.01 mol / L 2-(N-morpholine)ethanesulfonic acid MES buffer (pH = 5.2), stirred until completely dissolved, compound 123 (115 mg, 0.2 mmol) was weighed and dissolved in 10 mL dimethyl sulfoxide DMSO, and then added to the reaction solution, 4-(4,6-dimethoxytriazin-2-yl)-4-methylmorpholine hydrochloride DMTMM (0.4 g, 1.5 mmol) was weighed and dissolved in 3 mL MES buffer, and added to the reaction solution three times (once every hour), and reacted at 35 ° C for 24 hours. Then, the reaction solution was placed in a dialysis bag (MWCO 7000), dialyzed with deionized water for 2-3 days, and freeze-dried to obtain photosensitive carboxymethyl cellulose derivative A-103 (1.71 g). 1The labeling rate of compound 123 calculated based on the H-NMR spectrum was approximately 2.41%.

[0199] <Example 104> Synthesis of Component A-104 [ka] (1) Synthesis of Compound 137: Compound 137 was prepared by conventional chemical means according to the method of Example 88. 1 H NMR (400mHz, DMSO): δ= 7.71 (s, 1H), 7.17 (s, 1H),4.76 (s, 2H), 4.42 (m, 1H),3.97 (s, 3H),3.72 (d,J=6.3 Hz, 2H), 3.62 - 3.55 (m, 2H), 3.52-3.39 (m, 16H), 2.49 - 2.35 (m, 2H). MS (ESI): [M+Na] 533.1845. (2) Synthesis of component A-104: 1 g of chitosan was added to 75 mL of isopropanol to form a chitosan suspension, and then compound 137 (0.2 g, 0.35 mmol), EDC-HCl (0.76 g, 3.96 mmol) and NHS (0.46 g, 4.0 mmol) were added to the solution in that order, and the mixture was reacted at room temperature for 48 hours while stirring. After the reaction was completed, the mixture was dialyzed against a dilute hydrochloric acid solution (pH = 3.5) containing sodium chloride for one day, and then further dialyzed against pure water for one day, and freeze-dried to obtain photosensitive chitosan derivative A-104 (0.82 g). 1 The modification degree of compound 137 was calculated to be about 12.5% ​​based on the H-NMR spectrum.

[0200] <Example 105> Synthesis of Component A-105 [ka] (1) Synthesis of Compound 138: Compound 138 was prepared by conventional chemical means according to the method of Example 88. 1H NMR (400mHz, DMSO): δ= 7.71 (s, 1H), 7.17 (s, 1H),4.76 (s, 2H), 4.42 (m, 1H),4.13 (t, J=6.1 Hz, 2H), 3.93 (s, 3H),3.72 (d,J=6.3 Hz, MS (ESI): [M+Na] 640.1134. (2) Synthesis of component A-105: PEG-4OH (1g, 0.05mmol) was dissolved in anhydrous acetonitrile, K2CO3 (55.3mg, 0.4mmol) was added, and the mixture was stirred for 30 minutes. Compound 138 (0.23g, 0.4mmol) was then added and the mixture was allowed to react at room temperature for 24 hours. After the reaction was completed, most of the solvent was removed, the mixture was reprecipitated in diethyl ether, washed several times, filtered by suction, and dried to obtain the photosensitive polyethylene glycol derivative A-105 (0.85g). 1 The modification degree of compound 138 was calculated to be about 95.3% based on the H-NMR spectrum.

[0201] <Example 106> Synthesis of Component A-106 [ka] (1) Synthesis of Compound 139: Compound 139 was prepared by conventional chemical means according to the method of Example 88. 1H NMR (400mHz, DMSO): δ= 7.71 (s, 1H), 7.17 (s, 1H),6.25 (s, 1H), 5.68 (s, 1H), 4.76 (s, 2H), 4.42 (m, 1H),4.13 (t, J=6.1 Hz, 2H), 3.93 (s, 3H), 3.79 (t, J=6.1 Hz, 2H), 3.72 (d,J=6.3 Hz, 2H), 3.70 (t, J=7.2 Hz, 2H), 3.62 - 3.55 (m, 2H), 3.56 (t, J=7.2 Hz, 2H), 3.52-3.39 (m, 16H), 2.49 - 2.35 (m, 2H), 1.87 (s, 3H). MS (ESI): [M+Na] 689.2523. (2) Synthesis of component A-106: Compound 139 (0.28 g, 0.63 mmol), comonomer PEG-MA (0.882 g, 2.52 mmol) and initiator azobisisobutyronitrile (11 mg) were weighed and added to a Schreck flask, dissolved by adding anhydrous THF, and treated by multiple cycles of freezing and vacuuming. The reaction system was reacted for 24 hours under conditions of 75°C. After the reaction was completed, the reaction solution was put into cold diethyl ether and purified by multiple reprecipitations to obtain photosensitive copolymer derivative A-106 (0.85 g). 1 The content of compound 139 in the copolymer was calculated to be about 15.4% based on the H-NMR spectrum. The molecular weight of the synthetic polymer measured by GPC was about 25 kDa. As a result of calculation based on the blending ratio, n was 12, x was 10, and y was 40.

[0202] <Example 107> Synthesis of Component A-107 [ka] Synthesis of component A-107: Hyaluronic acid (1 g, 48 kDa) was dissolved in 100 mL of deionized water, cooled to 0-4°C, 4 mL of methacrylic anhydride was added, and 2 mL of 5 M NaOH was slowly added dropwise. After reacting for 24 hours, the reaction solution was placed in a dialysis bag (MWCO 3500), dialyzed against deionized water for 2-3 days, and freeze-dried to obtain photosensitive hyaluronic acid derivative A-107 (0.92 g). 1 The double bond content calculated based on the H-NMR spectrum was about 54%.

[0203] <Example 108> Synthesis of Component A-108 [ka] Synthesis of component A-108: Carboxymethyl cellulose (1 g, 90 kDa) was dissolved in 100 mL of deionized water, cooled to 0-4°C, 4 mL of methacrylic anhydride was added, and 2 mL of 5 M NaOH was slowly added dropwise. After reacting for 24 hours, the reaction solution was placed in a dialysis bag (MWCO 3500), dialyzed against deionized water for 2-3 days, and freeze-dried to obtain photosensitive carboxymethyl cellulose derivative A-108 (0.89 g). 1 The double bond content calculated based on the H-NMR spectrum was about 43%.

[0204] <Example 109> Synthesis of Component A-109 [ka] Synthesis of component A-109: Alginate (1 g, 48 kDa) was dissolved in 100 mL of deionized water, cooled to 0-4°C, 4 mL of methacrylic anhydride was added, and 2 mL of 5 M NaOH was slowly added dropwise. After reacting for 24 hours, the reaction solution was placed in a dialysis bag (MWCO 3500), dialyzed against deionized water for 2-3 days, and freeze-dried to obtain photosensitive alginic acid derivative A-109 (0.87 g). 1The double bond content calculated based on the H-NMR spectrum was about 57%.

[0205] <Example 110> Synthesis of Component A-110 [ka] Synthesis of component A-110: Chondroitin sulfate (1 g) was dissolved in 100 mL of deionized water, cooled to 0-4°C, and 4 mL of methacrylic anhydride was added. Then, 2 mL of 5M NaOH was slowly added dropwise and reacted for 24 hours. The reaction solution was then placed in a dialysis bag (MWCO 3500), dialyzed against deionized water for 2-3 days, and freeze-dried to obtain photosensitive chondroitin sulfate derivative A-110 (0.91 g). 1 The double bond content calculated based on the H-NMR spectrum was about 49%.

[0206] <Example 111> Synthesis of Component A-111 [ka] Synthesis of component A-111: glucan Dextran (6g, 70kDa) was dissolved in 60mL anhydrous dimethylsulfoxide (DMSO), 2mL triethylamine (TEA) was added, and then 0.56mL acryloyl chloride (dissolved in 10mL dichloromethane (DCM)) was added, and the mixture was reacted for 10 hours. After the reaction was completed, the reaction solution was put into ethanol to be reprecipitated, and the crude product obtained by filtration was dissolved again in deionized water, dialyzed for 2-3 days, and freeze-dried to obtain photosensitive glucan derivative A-111 (5.8g). 1 The double bond content calculated based on the H-NMR spectrum was about 24%.

[0207] <Example 112> Synthesis of Component A-112 [ka] Synthesis of component A-112: Carboxymethylchitosan (1 g) was dissolved in 100 mL of deionized water, heated to 40°C, stirred to dissolve, 4 mL of glycidyl methacrylate was added, and 2 mL of 5M NaOH was further added. After reacting for 2-3 hours, the reaction solution was placed in a dialysis bag (MWCO 3500), dialyzed against deionized water for 2-3 days, and freeze-dried to obtain photosensitive chitosan derivative A-112 (0.88 g). 1 The double bond content calculated based on the H-NMR spectrum was about 32%.

[0208] <Example 113> Synthesis of component A-113 [ka] Synthesis of component A-113: Dissolve gelatin (1 g) in 10 mL D-PBS and add 50 mL of o The mixture was heated to 30°C and stirred until completely dissolved, and 0.5mL methacrylic anhydride was added and reacted for 2-3 hours. The reaction solution was then diluted with 40mL D-PBS, placed in a dialysis bag (MWCO 3500) and dialyzed against deionized water for 2-3 days, and freeze-dried to obtain photosensitive gelatin derivative A-113 (0.93g). 1 The double bond content calculated based on the H-NMR spectrum was about 56%.

[0209] <Example 114> Synthesis of component A-114 [ka] Synthesis of component A-114: 2-arm hydroxypolyethylene glycol PEG (10 kDa, 10 g) was dissolved in dry dichloromethane, triethylamine (0.28 mL, 2 mmol) was added, and a dichloromethane solution of acryloyl chloride (0.18 g, 2 mmol) was slowly added dropwise to the solution, and the mixture was reacted for 12 hours with stirring. The reaction solution was then placed in a dialysis bag (MWCO 3500), dialyzed against deionized water for 2-3 days, and freeze-dried to obtain photosensitive polyethylene glycol derivative A-114 (9.8 g). 1 The double bond content calculated based on the H-NMR spectrum was about 98%.

[0210] <Example 115> Synthesis of Component A-115 [ka] Synthesis of component A-115: 4-arm hydroxypolyethylene glycol PEG (10 kDa, 10 g) was dissolved in dry dichloromethane, triethylamine (0.56 mL, 4 mmol) was added, and a dichloromethane solution of acryloyl chloride (0.36 g, 4 mmol) was slowly added dropwise to the solution, and the mixture was reacted for 12 hours with stirring. The reaction solution was then placed in a dialysis bag (MWCO 3500), dialyzed against deionized water for 2-3 days, and freeze-dried to obtain photosensitive polyethylene glycol derivative A-115 (9.3 g). 1 The double bond content calculated based on the H-NMR spectrum was about 96%.

[0211] <Example 116> Synthesis of Component A-116 [ka] Synthesis of component A-116: component A-1 is dissolved in 100mL deionized water, cooled to 0-4℃, 4mL methacrylic anhydride is added, and then 2mL 5M NaOH is slowly added dropwise. After reacting for 24 hours, the reaction solution is placed in a dialysis bag (MWCO 3500), dialyzed with deionized water for 2-3 days, and freeze-dried to obtain photosensitive hyaluronic acid derivative A-116 (0.91g) containing both o-nitrobenzyl and double bond functional groups. 1 The double bond content calculated based on the H-NMR spectrum was about 54%.

[0212] <Example 117> Synthesis of component A-117 [ka] Synthesis of component A-117: component A-2 is dissolved in 100mL deionized water, cooled to 0-4℃, 4mL methacrylic anhydride is added, and then 2mL 5M NaOH is slowly added dropwise. After reacting for 24 hours, the reaction solution is placed in a dialysis bag (MWCO 3500), dialyzed with deionized water for 2-3 days, and freeze-dried to obtain photosensitive hyaluronic acid derivative A-117 (0.87g) containing both o-nitrobenzyl and double bond functional groups. 1 The double bond content calculated based on the H-NMR spectrum was about 51%.

[0213] <Example 118> Synthesis of component A-118 [ka] Synthesis of component A-118: component A-8 is dissolved in 100mL deionized water, cooled to 0-4℃, 4mL methacrylic anhydride is added, and then 2mL 5M NaOH is slowly added dropwise. After reacting for 24 hours, the reaction solution is placed in a dialysis bag (MWCO 3500), dialyzed with deionized water for 2-3 days, and freeze-dried to obtain photosensitive hyaluronic acid derivative A-118 (0.86g) containing both o-nitrobenzyl and double bond functional groups. 1 The double bond content calculated based on the H-NMR spectrum was about 44%.

[0214] <Example 119> Synthesis of Component A-119 [ka] Synthesis of component A-119: component A-28 is dissolved in 100mL deionized water, cooled to 0-4℃, 4mL methacrylic anhydride is added, and then 2mL 5M NaOH is slowly added dropwise. After reacting for 24 hours, the reaction solution is placed in a dialysis bag (MWCO 3500), dialyzed with deionized water for 2-3 days, and freeze-dried to obtain photosensitive hyaluronic acid derivative A-119 (0.85g) containing both o-nitrobenzyl and double bond functional groups. 1 The double bond content calculated based on the H-NMR spectrum was about 43%.

[0215] <Example 120> Synthesis of Component A-120 [ka] Synthesis of component A-120: component A-29 was dissolved in 100mL deionized water, cooled to 0-4℃, and 4mL methacrylic anhydride was added, followed by slowly dripping 2mL 5M NaOH. After reacting for 24 hours, the reaction solution was placed in a dialysis bag (MWCO 3500), dialyzed with deionized water for 2-3 days, and freeze-dried to obtain photosensitive hyaluronic acid derivative A-120 (0.93g) containing both o-nitrobenzyl and double bond functional groups. 1 The double bond content calculated based on the H-NMR spectrum was about 55%.

[0216] <Example 121> Synthesis of component A-121 [ka] Synthesis of component A-121: component A-30 is dissolved in 100mL deionized water, cooled to 0-4℃, 4mL methacrylic anhydride is added, and then 2mL 5M NaOH is slowly added dropwise. After reacting for 24 hours, the reaction solution is placed in a dialysis bag (MWCO 3500), dialyzed with deionized water for 2-3 days, and freeze-dried to obtain photosensitive hyaluronic acid derivative A-121 (0.85g) containing both o-nitrobenzyl and double bond functional groups. 1 The double bond content calculated based on the H-NMR spectrum was about 49%.

[0217] <Example 122> Synthesis of component A-122 [ka] Synthesis of component A-122: Component A-37 was dissolved in 100mL deionized water, cooled to 0-4°C, and 4mL methacrylic anhydride was added, followed by slowly dropping 2mL 5M NaOH. After reacting for 24 hours, the reaction solution was placed in a dialysis bag (MWCO 3500), dialyzed against deionized water for 2-3 days, and freeze-dried to obtain photosensitive carboxymethylcellulose derivative A-122 (0.91g) containing both o-nitrobenzyl and double bond functional groups. 1 The double bond content calculated based on the H-NMR spectrum was about 42%.

[0218] <Example 123> Synthesis of component A-123 [ka] Synthesis of component A-123: Component A-43 was dissolved in 100 mL deionized water, cooled to 0-4°C, and 4 mL methacrylic anhydride was added, followed by slowly dropping 2 mL 5M NaOH. After reacting for 24 hours, the reaction solution was placed in a dialysis bag (MWCO 3500), dialyzed against deionized water for 2-3 days, and freeze-dried to obtain photosensitive chitosan derivative A-123 (0.84 g) containing both o-nitrobenzyl and double bond functional groups. 1 The double bond content calculated based on the H-NMR spectrum was about 56%.

[0219] <Example 124> Synthesis of component A-124 [ka] Synthesis of component A-124: Component A-45 was dissolved in 100mL deionized water, cooled to 0-4℃, 4mL methacrylic anhydride was added, and then 2mL 5M NaOH was slowly added dropwise. After reacting for 24 hours, the reaction solution was placed in a dialysis bag (MWCO 3500), dialyzed against deionized water for 2-3 days, and freeze-dried to obtain photosensitive gelatin derivative A-124 (0.92g) containing both o-nitrobenzyl and double bond functional groups. 1 The double bond content calculated based on the H-NMR spectrum was about 48%.

[0220] <Example 125> Synthesis of component A-125 [ka] Synthesis of component A-125: Component A-49 was dissolved in 100mL deionized water, cooled to 0-4°C, and 4mL methacrylic anhydride was added, followed by slowly dropping 2mL 5M NaOH. After reacting for 24 hours, the reaction solution was placed in a dialysis bag (MWCO 3500), dialyzed against deionized water for 2-3 days, and freeze-dried to obtain photosensitive polyethylene glycol derivative A-125 (0.94g) containing both o-nitrobenzyl and double bond functional groups. 1 The double bond content calculated based on the H-NMR spectrum was about 24%.

[0221] <Example 126> Synthesis of component A-126 [ka] Synthesis of component A-126: component A-51 was dissolved in 100mL deionized water, cooled to 0-4℃, 4mL methacrylic anhydride was added, and then 2mL 5M NaOH was slowly added dropwise. After reacting for 24 hours, the reaction solution was placed in a dialysis bag (MWCO 3500), dialyzed with deionized water for 2-3 days, and freeze-dried to obtain photosensitive hyaluronic acid derivative A-126 (0.87g) containing both o-nitrobenzyl and double bond functional groups. 1 The double bond content calculated based on the H-NMR spectrum was about 46%.

[0222] <Example 127> Synthesis of component A-127 [ka] Synthesis of component A-127: component A-52 was dissolved in 100mL deionized water, cooled to 0-4℃, 4mL methacrylic anhydride was added, and then 2mL 5M NaOH was slowly added dropwise. After reacting for 24 hours, the reaction solution was placed in a dialysis bag (MWCO 3500), dialyzed with deionized water for 2-3 days, and freeze-dried to obtain photosensitive hyaluronic acid derivative A-127 (0.85g) containing both o-nitrobenzyl and double bond functional groups. 1 The double bond content calculated based on the H-NMR spectrum was about 57%.

[0223] <Example 128> Synthesis of component A-128 [ka] Synthesis of component A-128: component A-53 was dissolved in 100mL deionized water, cooled to 0-4℃, 4mL methacrylic anhydride was added, and then 2mL 5M NaOH was slowly added dropwise. After reacting for 24 hours, the reaction solution was placed in a dialysis bag (MWCO 3500), dialyzed with deionized water for 2-3 days, and freeze-dried to obtain photosensitive hyaluronic acid derivative A-128 (0.93g) containing both o-nitrobenzyl and double bond functional groups. 1 The double bond content calculated based on the H-NMR spectrum was about 47%.

[0224] <Example 129> Synthesis of component A-129 [ka] Synthesis of component A-129: component A-62 was dissolved in 100mL deionized water, cooled to 0-4℃, 4mL methacrylic anhydride was added, and then 2mL 5M NaOH was slowly added dropwise. After reacting for 24 hours, the reaction solution was placed in a dialysis bag (MWCO 3500), dialyzed with deionized water for 2-3 days, and freeze-dried to obtain photosensitive hyaluronic acid derivative A-129 (0.90g) containing both o-nitrobenzyl and double bond functional groups. 1 The double bond content calculated based on the H-NMR spectrum was about 58%.

[0225] <Example 130> Synthesis of Component A-130 [ka] Synthesis of component A-130: component A-63 was dissolved in 100mL deionized water, cooled to 0-4℃, 4mL methacrylic anhydride was added, and then 2mL 5M NaOH was slowly added dropwise. After reacting for 24 hours, the reaction solution was placed in a dialysis bag (MWCO 3500), dialyzed with deionized water for 2-3 days, and freeze-dried to obtain photosensitive hyaluronic acid derivative A-130 (0.89g) containing both o-nitrobenzyl and double bond functional groups. 1 The double bond content calculated based on the H-NMR spectrum was about 46%.

[0226] <Example 131> Synthesis of component A-131 [ka] Synthesis of component A-131: component A-64 was dissolved in 100mL deionized water, cooled to 0-4℃, and 4mL methacrylic anhydride was added, followed by slowly dripping 2mL 5M NaOH. After reacting for 24 hours, the reaction solution was placed in a dialysis bag (MWCO 3500), dialyzed with deionized water for 2-3 days, and freeze-dried to obtain photosensitive hyaluronic acid derivative A-131 (0.87g) containing both o-nitrobenzyl and double bond functional groups. 1 The double bond content calculated based on the H-NMR spectrum was about 58%.

[0227] <Example 132> Synthesis of component A-132 [ka] Synthesis of component A-132: Component A-66 was dissolved in 100 mL deionized water, cooled to 0-4°C, and 4 mL methacrylic anhydride was added, followed by slowly dropping 2 mL 5M NaOH. After reacting for 24 hours, the reaction solution was placed in a dialysis bag (MWCO 3500), dialyzed with deionized water for 2-3 days, and freeze-dried to obtain photosensitive carboxymethylcellulose derivative A-132 (0.92 g) containing both o-nitrobenzyl and double bond functional groups. 1 The double bond content calculated based on the H-NMR spectrum was about 46%.

[0228] <Example 133> Synthesis of component A-133 [ka] Synthesis of component A-133: Component A-67 was dissolved in 100 mL deionized water, cooled to 0-4°C, and 4 mL methacrylic anhydride was added, followed by slowly dropping 2 mL 5M NaOH. After reacting for 24 hours, the reaction solution was placed in a dialysis bag (MWCO 3500), dialyzed against deionized water for 2-3 days, and freeze-dried to obtain photosensitive chitosan derivative A-133 (0.91 g) containing both o-nitrobenzyl and double bond functional groups. 1 The double bond content calculated based on the H-NMR spectrum was about 47%.

[0229] <Example 134> Synthesis of component A-134 [ka] Synthesis of component A-134: Component A-68 was dissolved in 100 mL deionized water, cooled to 0-4°C, and 4 mL methacrylic anhydride was added, followed by slowly dropping 2 mL 5M NaOH. After reacting for 24 hours, the reaction solution was placed in a dialysis bag (MWCO 3500), dialyzed against deionized water for 2-3 days, and freeze-dried to obtain photosensitive polyethylene glycol derivative A-134 (0.87 g) containing both o-nitrobenzyl and double bond functional groups. 1 The double bond content calculated based on the H-NMR spectrum was about 52%.

[0230] <Example 135> Synthesis of component A-135 [ka] Synthesis of component A-135: component A-70 was dissolved in 100mL deionized water, cooled to 0-4℃, 4mL methacrylic anhydride was added, and then 2mL 5M NaOH was slowly added dropwise. After reacting for 24 hours, the reaction solution was placed in a dialysis bag (MWCO 3500), dialyzed with deionized water for 2-3 days, and freeze-dried to obtain photosensitive hyaluronic acid derivative A-135 (0.92g) containing both o-nitrobenzyl and double bond functional groups. 1 The double bond content calculated based on the H-NMR spectrum was about 47%.

[0231] <Example 136> Synthesis of Component A-136 [ka] Synthesis of component A-136: component A-71 was dissolved in 100mL deionized water, cooled to 0-4℃, 4mL methacrylic anhydride was added, and then 2mL 5M NaOH was slowly added dropwise. After reacting for 24 hours, the reaction solution was placed in a dialysis bag (MWCO 3500), dialyzed with deionized water for 2-3 days, and freeze-dried to obtain photosensitive hyaluronic acid derivative A-136 (0.86g) containing both o-nitrobenzyl and double bond functional groups. 1 The double bond content calculated based on the H-NMR spectrum was about 51%.

[0232] <Example 137> Synthesis of component A-137 [ka] Synthesis of component A-137: component A-72 was dissolved in 100mL deionized water, cooled to 0-4℃, 4mL methacrylic anhydride was added, and then 2mL 5M NaOH was slowly added dropwise. After reacting for 24 hours, the reaction solution was placed in a dialysis bag (MWCO 3500), dialyzed with deionized water for 2-3 days, and freeze-dried to obtain photosensitive hyaluronic acid derivative A-137 (0.93g) containing both o-nitrobenzyl and double bond functional groups. 1 The double bond content calculated based on the H-NMR spectrum was about 45%.

[0233] <Example 138> Synthesis of component A-138 [ka] Synthesis of component A-138: component A-80 was dissolved in 100mL deionized water, cooled to 0-4℃, 4mL methacrylic anhydride was added, and then 2mL 5M NaOH was slowly added dropwise. After reacting for 24 hours, the reaction solution was placed in a dialysis bag (MWCO 3500), dialyzed with deionized water for 2-3 days, and freeze-dried to obtain photosensitive hyaluronic acid derivative A-138 (0.90g) containing both o-nitrobenzyl and double bond functional groups. 1 The double bond content calculated based on the H-NMR spectrum was about 48%.

[0234] <Example 139> Synthesis of component A-139 [ka] Synthesis of component A-139: component A-81 was dissolved in 100mL deionized water, cooled to 0-4℃, 4mL methacrylic anhydride was added, and then 2mL 5M NaOH was slowly added dropwise. After reacting for 24 hours, the reaction solution was placed in a dialysis bag (MWCO 3500), dialyzed with deionized water for 2-3 days, and freeze-dried to obtain photosensitive hyaluronic acid derivative A-139 (0.88g) containing both o-nitrobenzyl and double bond functional groups. 1 The double bond content calculated based on the H-NMR spectrum was about 46%.

[0235] <Example 140> Synthesis of Component A-140 [ka] Synthesis of component A-140: component A-82 was dissolved in 100mL deionized water, cooled to 0-4℃, 4mL methacrylic anhydride was added, and then 2mL 5M NaOH was slowly added dropwise. After reacting for 24 hours, the reaction solution was placed in a dialysis bag (MWCO 3500), dialyzed with deionized water for 2-3 days, and freeze-dried to obtain photosensitive hyaluronic acid derivative A-140 (0.91g) containing both o-nitrobenzyl and double bond functional groups. 1 The double bond content calculated based on the H-NMR spectrum was about 57%.

[0236] <Example 141> Synthesis of component A-141 [ka] Synthesis of component A-141: Component A-84 was dissolved in 100mL deionized water, cooled to 0-4°C, and 4mL methacrylic anhydride was added, followed by slowly dropping 2mL 5M NaOH. After reacting for 24 hours, the reaction solution was placed in a dialysis bag (MWCO 3500), dialyzed against deionized water for 2-3 days, and freeze-dried to obtain photosensitive carboxymethylcellulose derivative A-141 (0.92g) containing both o-nitrobenzyl and double bond functional groups. 1 The double bond content calculated based on the H-NMR spectrum was about 44%.

[0237] <Example 142> Synthesis of component A-142 [ka] Synthesis of component A-142: Component A-85 was dissolved in 100 mL deionized water, cooled to 0-4°C, and 4 mL methacrylic anhydride was added, followed by slowly dropping 2 mL 5M NaOH. After reacting for 24 hours, the reaction solution was placed in a dialysis bag (MWCO 3500), dialyzed against deionized water for 2-3 days, and freeze-dried to obtain photosensitive chitosan derivative A-142 (0.87 g) containing both o-nitrobenzyl and double bond functional groups. 1 The double bond content calculated based on the H-NMR spectrum was about 56%.

[0238] <Example 143> Synthesis of component A-143 [ka] Synthesis of component A-143: Component A-86 was dissolved in 100mL deionized water, cooled to 0-4°C, and 4mL methacrylic anhydride was added, followed by slowly dropping 2mL 5M NaOH. After reacting for 24 hours, the reaction solution was placed in a dialysis bag (MWCO 3500), dialyzed against deionized water for 2-3 days, and freeze-dried to obtain photosensitive polyethylene glycol derivative A-143 (0.91g) containing both o-nitrobenzyl and double bond functional groups. 1The double bond content calculated based on the H-NMR spectrum was about 48%.

[0239] <Example 144> Synthesis of component A-144 [ka] Synthesis of component A-144: component A-88 was dissolved in 100mL deionized water, cooled to 0-4℃, 4mL methacrylic anhydride was added, and then 2mL 5M NaOH was slowly added dropwise. After reacting for 24 hours, the reaction solution was placed in a dialysis bag (MWCO 3500), dialyzed with deionized water for 2-3 days, and freeze-dried to obtain photosensitive hyaluronic acid derivative A-144 (0.89g) containing both o-nitrobenzyl and double bond functional groups. 1 The double bond content calculated based on the H-NMR spectrum was about 52%.

[0240] <Example 145> Synthesis of component A-145 [ka] Synthesis of component A-145: component A-89 was dissolved in 100mL deionized water, cooled to 0-4℃, 4mL methacrylic anhydride was added, and then 2mL 5M NaOH was slowly added dropwise. After reacting for 24 hours, the reaction solution was placed in a dialysis bag (MWCO 3500), dialyzed with deionized water for 2-3 days, and freeze-dried to obtain photosensitive hyaluronic acid derivative A-145 (0.81g) containing both o-nitrobenzyl and double bond functional groups. 1 The double bond content calculated based on the H-NMR spectrum was about 43%.

[0241] <Example 146> Synthesis of Component A-146 [ka] Synthesis of component A-146: component A-90 was dissolved in 100mL deionized water, cooled to 0-4℃, 4mL methacrylic anhydride was added, and then 2mL 5M NaOH was slowly added dropwise. After reacting for 24 hours, the reaction solution was placed in a dialysis bag (MWCO 3500), dialyzed with deionized water for 2-3 days, and freeze-dried to obtain photosensitive hyaluronic acid derivative A-146 (0.84g) containing both o-nitrobenzyl and double bond functional groups. 1 The double bond content calculated based on the H-NMR spectrum was about 49%.

[0242] <Example 147> Synthesis of component A-147 [ka] Synthesis of component A-147: component A-91 was dissolved in 100mL deionized water, cooled to 0-4℃, and 4mL methacrylic anhydride was added, followed by slowly dripping 2mL 5M NaOH. After reacting for 24 hours, the reaction solution was placed in a dialysis bag (MWCO 3500), dialyzed with deionized water for 2-3 days, and freeze-dried to obtain photosensitive hyaluronic acid derivative A-147 (0.92g) containing both o-nitrobenzyl and double bond functional groups. 1 The double bond content calculated based on the H-NMR spectrum was about 46%.

[0243] <Example 148> Synthesis of component A-148 [ka] Synthesis of component A-148: component A-98 was dissolved in 100mL deionized water, cooled to 0-4℃, and 4mL methacrylic anhydride was added, followed by slowly dripping 2mL 5M NaOH. After reacting for 24 hours, the reaction solution was placed in a dialysis bag (MWCO 3500), dialyzed with deionized water for 2-3 days, and freeze-dried to obtain photosensitive hyaluronic acid derivative A-148 (0.94g) containing both o-nitrobenzyl and double bond functional groups. 1 The double bond content calculated based on the H-NMR spectrum was about 56%.

[0244] <Example 149> Synthesis of component A-149 [ka] Synthesis of component A-149: component A-99 was dissolved in 100mL deionized water, cooled to 0-4℃, and 4mL methacrylic anhydride was added, followed by slowly dripping 2mL 5M NaOH. After reacting for 24 hours, the reaction solution was placed in a dialysis bag (MWCO 3500), dialyzed with deionized water for 2-3 days, and freeze-dried to obtain photosensitive hyaluronic acid derivative A-149 (0.87g) containing both o-nitrobenzyl and double bond functional groups. 1 The double bond content calculated based on the H-NMR spectrum was about 51%.

[0245] <Example 150> Synthesis of Component A-150 [ka] Synthesis of component A-150: component A-100 was dissolved in 100mL deionized water, cooled to 0-4℃, 4mL methacrylic anhydride was added, and then 2mL 5M NaOH was slowly added dropwise. After reacting for 24 hours, the reaction solution was placed in a dialysis bag (MWCO 3500), dialyzed with deionized water for 2-3 days, and freeze-dried to obtain photosensitive hyaluronic acid derivative A-150 (0.88g) containing both o-nitrobenzyl and double bond functional groups. 1 The double bond content calculated based on the H-NMR spectrum was about 47%.

[0246] <Example 151> Synthesis of Component A-151 [ka] Synthesis of component A-151: component A-101 was dissolved in 100mL deionized water, cooled to 0-4℃, and 4mL methacrylic anhydride was added, followed by slowly dripping 2mL 5M NaOH. After reacting for 24 hours, the reaction solution was placed in a dialysis bag (MWCO 3500), dialyzed with deionized water for 2-3 days, and freeze-dried to obtain photosensitive hyaluronic acid derivative A-151 (0.91g) containing both o-nitrobenzyl and double bond functional groups. 1 The double bond content calculated based on the H-NMR spectrum was about 45%.

[0247] <Example 152> Synthesis of component A-152 [ka] Synthesis of component A-152: Component A-103 was dissolved in 100mL deionized water, cooled to 0-4°C, and 4mL methacrylic anhydride was added, followed by slowly dropping 2mL 5M NaOH. After reacting for 24 hours, the reaction solution was placed in a dialysis bag (MWCO 3500), dialyzed with deionized water for 2-3 days, and freeze-dried to obtain photosensitive carboxymethylcellulose derivative A-152 (0.84g) containing both o-nitrobenzyl and double bond functional groups. 1 The double bond content calculated based on the H-NMR spectrum was about 43%.

[0248] <Example 153> Synthesis of component A-153 [ka] Synthesis of component A-153: Component A-104 was dissolved in 100 mL deionized water, cooled to 0-4°C, and 4 mL methacrylic anhydride was added, followed by slowly dropping 2 mL 5M NaOH. After reacting for 24 hours, the reaction solution was placed in a dialysis bag (MWCO 3500), dialyzed against deionized water for 2-3 days, and freeze-dried to obtain photosensitive chitosan derivative A-153 (0.89 g) containing both o-nitrobenzyl and double bond functional groups. 1 The double bond content calculated based on the H-NMR spectrum was about 50%.

[0249] <Example 154> Synthesis of component A-154 [ka] Synthesis of component A-154: Component A-105 was dissolved in 100mL deionized water, cooled to 0-4°C, and 4mL methacrylic anhydride was added, followed by slowly dropping 2mL 5M NaOH. After reacting for 24 hours, the reaction solution was placed in a dialysis bag (MWCO 3500), dialyzed against deionized water for 2-3 days, and freeze-dried to obtain photosensitive polyethylene glycol derivative A-154 (0.94g) containing both o-nitrobenzyl and double bond functional groups. 1 The double bond content calculated based on the H-NMR spectrum was about 43%.

[0250] <Example 155> Synthesis of photoinitiator-LAP [ka] Synthesis of LAP: Dimethoxyphenylphosphine (3.0g, 0.018mol) was placed in a 250mL three-neck flask, and 2,4,6-trimethylbenzoyl chloride (3.2g, 0.018mol) was added under argon protection, and the mixture was reacted for 18 hours at room temperature with stirring. Lithium bromide (6.1g, 0.072mol) was dissolved in 100mL of 2-butanone, and added to the reaction solution. The mixture was heated to 50°C and reacted for 10 minutes to form a precipitate. The mixture was then cooled to room temperature and allowed to stand for 4 hours. The mixture was then filtered, and the resulting crude product was washed several times with 2-butanone and dried to obtain white solid LAP (6.0g).

[0251] <Example 156> Synthesis of component C-10 [ka] Synthesis of component C-10: Carboxymethylcellulose CMC (400 mg) was completely dissolved in 50 mL distilled water, and hydroxybenzotriazole (HOBt, 153 mg), dihydrazine (90 mg) and 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC-HCl, 90 mg) were added to the solution, and the mixture was reacted at room temperature for 48 hours. The mixture was then dialyzed for one day against a dilute hydrochloric acid solution (pH = 3.5) containing sodium chloride, and then dialyzed for another day against pure water, and freeze-dried to obtain hydrazine-modified carboxymethylcellulose (410 mg). The hydrazine grafting rate measured by the TBNS method was about 10%.

[0252] <Example 157> Synthesis of component C-11 [ka] Synthesis of component C-11: Hyaluronic acid HA (400mg) was completely dissolved in 50mL distilled water, and hydroxybenzotriazole (HOBt, 153mg), carbohydrazide (CDH, 90mg) and 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC-HCl, 90mg) were added to the solution, and the mixture was reacted at room temperature for 48 hours. After that, the mixture was dialyzed with a dilute hydrochloric acid solution (pH=3.5) containing sodium chloride for one day, and then dialyzed with pure water for another day, and freeze-dried to obtain HA-CDH (410mg). The grafting rate of acylhydrazine measured by the TBNS method was about 10%.

[0253] <Example 158> Synthesis of component C-12 [ka] Synthesis of component C-12: Hyaluronic acid HA (400mg) was completely dissolved in 50mL distilled water, and hydroxybenzotriazole (HOBt, 153mg), oxalic acid dihydrazide (ODH, 90mg) and 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC-HCl, 90mg) were added to the solution, and the mixture was reacted at room temperature for 48 hours, and then the mixture was dialyzed with a dilute hydrochloric acid solution (pH=3.5) containing sodium chloride for one day, and then dialyzed with pure water for one day, and then freeze-dried to obtain HA-ODH (410mg). The grafting rate of acylhydrazine measured by the TBNS method was about 10%.

[0254] <Example 159> Synthesis of component C-13 [ka] Synthesis of component C-13: Hyaluronic acid HA (400mg) was completely dissolved in 50mL distilled water, and hydroxybenzotriazole (HOBt, 153mg), adipic acid dihydrazide (ADH, 90mg) and 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC-HCl, 90mg) were added to the solution, and the mixture was reacted at room temperature for 48 hours, then dialyzed with a dilute hydrochloric acid solution (pH=3.5) containing sodium chloride for one day, and then dialyzed with pure water for another day, and then freeze-dried to obtain HA-ADH (410mg). The grafting rate of acylhydrazine measured by the TBNS method was about 10%.

[0255] <Example 160> Synthesis of component C-14 [ka] Synthesis of component C-14: 4-arm hydroxypolyethylene glycol (PEG-4OH, 2 g, 97.3 μmol) and N-hydroxyphthalimide (634.6 mg, 3.89 mmol) were weighed and dissolved in dry dichloromethane, then triphenylphosphine (1.02 g, 3.89 mmol) was slowly added under ice bath conditions and reacted for about 30 minutes. Diisopropyl azodicarboxylate (765.9 μL, 3.89 mmol) was dissolved in dry dichloromethane and slowly added dropwise to the solution, and reacted at room temperature for one day. After the reaction was completed, the 4-arm polyethylene glycol modified with N-hydroxyphthalimide was reprecipitated with diethyl ether. Then, the material (0.25 g, 11.8 μmol) was dissolved again in acetonitrile, hydrazine monohydrate (22.9 μL, 473 μmol) was added, and the mixture was stirred for 2 hours. Then, dichloromethane was added to the mixture solution and suction filtered. The solvent was removed by rotary evaporation of the filtrate under reduced pressure to give hydroxylamine-modified 4-arm polyethylene glycol (PEG-4ONH2).

[0256] <Example 161> Synthesis of component C-15 [ka] Synthesis of component C-15: glucan (Dextran, 2 g, 97.3 μmol) and N-hydroxyphthalimide (634.6 mg, 3.89 mmol) were weighed and dissolved in dry dichloromethane, then triphenylphosphine (1.02 g, 3.89 mmol) was slowly added under ice bath conditions and reacted for about 30 minutes. Diisopropyl azodicarboxylate (765.9 μL, 3.89 mmol) was dissolved in dry dichloromethane and slowly added dropwise to the solution, and reacted at room temperature for one day. After the reaction was completed, the glucan modified with N-hydroxyphthalimide was reprecipitated with diethyl ether. Then, the substance (0.25 g, 11.8 μmol) was dissolved again in acetonitrile, hydrazine monohydrate (22.9 μL, 473 μmol) was added, and the mixture was stirred for 2 hours. Then, dichloromethane was added to the mixture solution and suction filtered. The filtrate was rotary evaporated under reduced pressure to remove the solvent, yielding the hydroxylamine-modified glucan (Dex-ONH2).

[0257] <Example 162> Synthesis of component C-18 [ka] Synthesis of component C-18: Hyaluronic acid (0.5g, 48kDa) was completely dissolved in 50mL distilled water, hydroxybenzotriazole (HOBt, 0.2g), 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC-HCl, 0.1g), 3,3'-dithiobis(propionylhydrazide) (DTP, 0.1g) were added, and the pH of the solution was adjusted to 4.75 with dilute hydrochloric acid. After reacting for 24 hours, DTT was added and the reaction was continued for 5 hours. The reaction solution was then placed in a dialysis bag (MWCO 3500), dialyzed against deionized water for 2-3 days, and freeze-dried to obtain HA-SH (0.45g). 1 The content of mercapto groups calculated based on the H-NMR spectrum was approximately 20%.

[0258] <Example 163> Synthesis of component C-19 [ka] Synthesis of component C-19: Carboxymethyl chitosan (1 g) was dissolved in 100 mL deionized water, N-acetylcysteine ​​(1.77 g, 10 mmol) was added, and 1-ethyl-(3-dimethylaminopropyl) carbodiimide hydrochloride EDC-HCl (1.91 g, 10 mmol) was further added. Next, the pH was adjusted to about 5 with hydrochloric acid, and the mixture was reacted at room temperature for 5 hours with stirring. The reaction solution was then placed in a dialysis bag (MWCO 3500) and dialyzed against 5 mM HCl solution for one day, then against 5 mM HCl / 1% NaCl solution for one day, and finally against 1 mM HCl solution for one day. The mixture was then freeze-dried to obtain CMCh-SH (0.9 g). 1 The content of mercapto groups calculated based on the H-NMR spectrum was approximately 10%.

[0259] <Example 164> Synthesis of component C-20 [ka] Synthesis of component C-20: 40 kDa glucan Dextran (12 g, 0.3 mmol) was completely dissolved in 50 mL DMSO, 3-mercaptopropionic acid (636.8 mg, 6.0 mmol), 1,3-dicyclohexylcarbodiimide (910.7 mg, 9.0 mmol), 4-(dimethylamino)pyridine (1099.5 mg, 9.0 mmol) were added, and the mixture was reacted at room temperature for 48 hours. The mixture was then reprecipitated in acetone, and the crude product was dissolved in water and placed in a dialysis bag (MWCO 3500), dialyzed against deionized water for 2-3 days, and freeze-dried to obtain Dex-SH (11.5 g). 1 The content of mercapto groups calculated based on the H-NMR spectrum was approximately 20%.

[0260] <Example 165> Synthesis of component C-21 [ka] Synthesis of component C-21: Heparin (0.5 g, 12 kDa) was completely dissolved in 50 mL of distilled water, and hydroxybenzotriazole (HOBt, 0.2 g), 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC-HCl, 0.1 g), and mercaptoethylamine (0.1 g) were added. The pH was adjusted to 5-6 with dilute hydrochloric acid solution, and the mixture was reacted for 24 hours. The reaction solution was then placed in a dialysis bag (MWCO 3500), dialyzed against deionized water for 2-3 days, and freeze-dried to obtain Hep-SH (0.45 g). 1 The content of mercapto groups calculated based on the H-NMR spectrum was approximately 20%.

[0261] <Example 166> Preparation of hydrogel by photocrosslinking method Different hydrogel precursor solutions shown in Table 1 were prepared by the method of the present invention at 37°C. [Table 1]

[0262] The different gel solutions were prepared using 365 or 395 nm (20 mW / cm 2 ) for a certain period of time, hydrogels with different chemical compositions were obtained. Different gel materials have different biological effects, so the composition of the gel material can be targeted and selected according to the application.

[0263] Note: Component A... indicates components A-2 to A-153. Component A... indicates components A-1 to A-154. Component C... indicates components C-1 to C-21.

[0264] In Table 1, 1-20 wt % is the preferred mass concentration range for the hydrogel precursor solution.

[0265] Example 167: Rheological test of photocrosslinkable hydrogel Rheological analysis was performed using a HAAKE MARS rheometer on a test platform (φ=20 mm) at 37° C. In this example, the effects of UV light irradiation time, light irradiation intensity, and mass concentration of the polymer derivative on the gelation time and storage modulus of the hydrogel were investigated. FIG. 1 shows the gelation curves of the hydrogel precursor solutions prepared from component A-1 (i.e., HA-NB) prepared in Example 1, component A-107 (i.e., HAMA) prepared in Example 107, component C-4 (i.e., gelatin), component B-2 (i.e., LAP) prepared in Example 155, component A-88 (i.e., HA-cNB) prepared in Example 88, component A-144 (i.e., HA-cNB-MA) prepared in Example 144, and component B-2 (i.e., LAP) prepared in Example 155, when irradiated with light (in the rheological test, G' is the storage modulus, G'' is the loss modulus, and the point at which G' exceeds G'' is the gel point). Thus, both the gelation rate and gel strength are superior to those of hydrogels constructed by simple radical polymerization crosslinking and photo-bonding crosslinking. As can be seen from Figure 1, the solution begins to gel at about 2 s, is completely gelled at about 10 s, and the elastic modulus at the time of complete gelation reaches 3500-10000 Pa. Furthermore, the strength of the gel is proportional to the mass concentration of the gel solution, the higher the mass concentration of the gel, the stronger the gel obtained. The gel points and gel strengths of other hydrogel systems with different material compositions are different, and the specific data are shown in Table 2.

[0266] [Table 2a] [Table 2b] [Table 2c] Note: NB0 is an o-nitrobenzyl-based phototrigger used in the preparation of hydrogels, as disclosed in the literature (Yunlong Yang; Jieyuan Zhang; Zhenzhen Liu; Qiuning Lin; Xiaolin Liu; Chunyan Bao; Yang Wang; Linyong Zhu. Adv. Mater. 2016, 28, 2724.). HA-NB0 is a hyaluronic acid polymer derivative labeled with NB0. NB is an o-nitrobenzyl-based phototrigger in component A-1 of the present invention. cNB is a cyclic o-nitrobenzyl-based phototrigger in component A-88 of the present invention. cNB-MA is a component containing both a cyclic o-nitrobenzyl-based phototrigger and a double bond functional group in component A-144 of the present invention. HA-NB is component A-1, HA-cNB is component A-88, and HA-cNB-MA is component A-144.

[0267] Example 168: Adhesion test of photocrosslinkable hydrogel Several fresh porcine intestinal casings were taken and cut into 3.5 cm × 2.5 cm casing pieces. They were then fixed to 6.5 cm × 2.5 cm tempered glass slices with 502 adhesive. One glass slice was taken and 150 μL of a fixed-component hydrogel precursor solution was applied to the surface of the intestinal casing that was glued to it. Next, another tempered glass slice was taken and placed on the glass slice on which the hydrogel precursor solution had been applied, with the intestinal casing positioned completely opposite. The excess extruded hydrogel precursor solution was then removed. Next, a 395 nm LED light source (20 mW / cm 2 ) was used to irradiate the intestinal casing site for 5 minutes, and the hydrogel precursor solution was gelled in situ between the two intestinal casings. After complete gelation, one end of the glass slice was fixed vertically, and the other end was connected to a water container via a string. Water was then added to the container until the two glass slices broke. The mass of the water and the container at the time of breakage was then recorded and converted into gravity, i.e., the tensile force F at the time the glass slice broke, and the tissue adhesive force of the hydrogel was calculated using the following formula. Adhesion strength of hydrogel to tissue = F / A Wherein, A is the adhesive area of ​​the intestinal casing. The schematic diagram of the test apparatus is shown in Figure 2. The tissue adhesive force of hydrogel systems with different material compositions is different, and the specific data is shown in Table 3.

[0268] [Table 3a] [Table 3b] [Table 3c] <Example 169> Mechanical performance test of photocrosslinkable hydrogel Mechanical performance tests (including tensile tests and compression tests) were performed using a GT-TCS-2000 tensile tester. For the tensile tests, dumbbell-shaped specimens with a length of 20 mm, width of 3 mm, and thickness of 2 mm were used, and the test speed was set to 5 mm / min. For the compression tests, cylindrical specimens with a diameter of 10 mm and height of 3 mm were used, and the test speed was set to 1 mm / min. The tensile properties and compression performance of the hydrogels were measured using the component A-1 (i.e., HA-NB) prepared in Example 1, the component A-107 (i.e., HAMA) prepared in Example 107, the component C-4 (i.e., gelatin), the component B-2 (i.e., LAP) prepared in Example 155, the component A-88 (i.e., HA-cNB) prepared in Example 88, the component A-144 (i.e., HA-cNB-MA) prepared in Example 144, and the component B-2 (i.e., LAP) prepared in Example 155 as examples. As can be seen from Figure 3, the hydrogel (HA-NB / HAMA / Gelatin / LAP) can be compressed to about 75% and has a compressive strength of about 2 MPa, and the hydrogel (HA-cNB / HA-cNB-MA / LAP) can be compressed to about 88% and has a compressive strength of about 1 MPa. The mechanical performance of hydrogel systems with different material compositions is different, and the specific data is shown in Table 4.

[0269] [Table 4a] [Table 4b] [Table 4c]

[0270] Example 170: Biocompatibility test of photocrosslinkable hydrogel In this experiment, component A-1 (i.e., HA-NB) prepared in Example 1, component A-107 (i.e., HAMA) prepared in Example 107, component C-4 (i.e., gelatin), component B-2 (i.e., LAP) prepared in Example 155, component A-88 (i.e., HA-cNB) prepared in Example 88, component A-144 (i.e., HA-cNB-MA) prepared in Example 144, and component B-2 (i.e., LAP) prepared in Example 155 were evaluated using a CCK-8 kit. First, 5×10 3 After seeding fibroblast HDF at a density of cells / well, medium was added and cultured for 24 hours under conditions of 37°C / 5% CO2. Each group of samples was dissolved in cell culture medium and added to the well plate in which the cells were cultured. After further culture for 24 hours, the cell liquid in the well was aspirated, 100 μL of medium and 10 μL of CCK-8 solution were added to each well, and the cells were then incubated for 2 hours. Finally, the absorbance at 450 nm was measured for each well using a microplate reader. The cell viability was calculated using the following formula: Cell viability (%) = (mean absorbance of experimental group / mean absorbance of control group) x 100% As can be seen from FIG. 4, this photocrosslinkable hydrogel has relatively good biocompatibility.

[0271] In an in vivo immune inflammatory response test, the hydrogels prepared in Example 1 (i.e., HA-NB), Example 107 (i.e., HAMA), Example 155 (i.e., LAP), Example 155 (i.e., LAP), Example 155 (i.e., A-88), Example 88 (i.e., HA-cNB), Example 144 (i.e., HA-cNB-MA), and Example 155 (i.e., B-2) were subcutaneously inoculated into rabbits, and the inflammatory response caused by the hydrogel in vivo was analyzed by staining tissue sections at different time points. The biocompatibility of other hydrogel systems with different material compositions is different, and specific data are shown in Table 5.

[0272] [Table 5a] [Table 5b] In all of the above different component hydrogel materials, the ratio of component A to component B is 2% wt:0.2% wt, and the ratio of component A to component B to component C is 2% wt:0.2% wt:2% wt.

[0273] Example 171: Wound closure - Use of photocrosslinkable hydrogels in skin repair In the experiment, a complete skin defect wound with a diameter of 1.8 cm was created on the dorsal skin of SD rats. Then, 400 μL of hydrogel precursor solution (2% component A-1 / 1% component A-107 / 6% component C-4 / 0.2% component B-2) was filled into the wound site. Since this solution has good fluidity, the wound can be sufficiently filled and permeated with the hydrogel precursor solution. Then, the wound was closed by forming a hydrogel in situ at the defect site of the skin by irradiation with a 395 nm LED light source (Figure 5). Furthermore, the repair effect of the dorsal skin wound of SD rats within 7 days by the in situ formed hydrogel, the preformed hydrogel, and the washing treatment with only physiological saline was compared. As a result, the speed of wound repair by the in situ formed hydrogel was obviously faster than the other two groups, the contraction area of ​​the wound on the 7th day was the largest, and a good repair effect was achieved. In contrast, the preformed hydrogel material was difficult to fill the wound site sufficiently. In addition, there is no covalently bonded gap-free interface between tissues, so it does not have good tissue integration. It is difficult for new cells and tissues to quickly enter the hydrogel material and fully play the role of a scaffolding material. Therefore, the repair speed and effect of pre-formed hydrogels are worse than those of in situ formed hydrogels. The wounds not filled with hydrogels have the slowest repair speed, indicating that photocrosslinkable hydrogels have a promoting effect on wound repair as a cell scaffolding material.

[0274] Other hydrogel systems with different material compositions (component A: component A-1 to component A-154, component B: component B-1 to component B-3, component C-1 to C-21) belong to photocrosslinkable hydrogels and can be similarly applied to wound closure-skin repair.

[0275] Example 172: Wound closure - Use of photocrosslinkable hydrogel in preventing postoperative adhesions In the experiment, an intraperitoneal adhesion model was constructed by abdominal wall-cecum friction using SD rats. The cecum is the thickest part in the abdominal cavity, has the most passages, and is the most vascularized part. If no measures are taken while damage occurs to the corresponding abdominal wall, the probability of intraperitoneal adhesion occurring is extremely high, so the constructed adhesion model is stable. During the surgery, the hydrogel precursor solution (2% component A-1 / 1% component A-107 / 6% component C-4 / 0.2% component B-2) can sufficiently cover the wound of the cecum and abdominal wall, and can stagnate on the vertical tissue surface for a sufficient time for gelation by light irradiation. After 30 seconds of light irradiation, the obtained hydrogel is fixed to the wound site, and the hydrogel cannot be peeled off from the wound site even if a certain force is applied with a scalpel. The time from administration of the hydrogel precursor solution to complete gelation can be controlled within 1 minute (Figure 6). After the operation, the SD rats were kept in a sterile environment for 14 days, and the abdominal cavity of the SD rats was opened again to record the intraperitoneal adhesions. Of the 10 rats in the experimental group treated with hydrogel, 8 did not develop intestinal-abdominal wall adhesions or intestinal-intestinal adhesions after 14 days, 1 developed moderate adhesions between the abdominal wall and cecum, and 1 developed thin adhesions between the intestines. In addition, no hydrogel residue was observed in the 9 SD rats that did not develop intestinal-abdominal wall adhesions, and the wounds on the abdominal wall were completely healed. In contrast, all 10 rats in the control group developed severe abdominal wall-cecum adhesions. Next, histological analysis was performed on tissue sections from the wounds from the operation in the experimental and control groups by H&E staining. In the SD rats in the experimental group, the damage to the cecum and abdominal wall was almost completely recovered after 14 days, and the surface layer was re-epithelialized. On the other hand, in the control SD rats, after 14 days, the smooth muscle of the cecum and the muscle tissue of the abdominal wall had completely fused, and fibroblasts and inflammatory cells had accumulated at the adhesion site.

[0276] Other hydrogel systems with different material compositions (component A: component A-1 to component A-154, component B: component B-1 to component B-3, component C-1 to C-21) belong to photocrosslinkable hydrogels and can be similarly applied to wound closure and prevention of postoperative adhesions.

[0277] Example 173: Wound closure - Use of photocrosslinkable hydrogels in oral ulcers In the experiment, an oral ulcer defect wound with a diameter of 1.0 cm was created in the oral cavity of an SD rat. Then, 200 μL of hydrogel precursor solution (2% component A-1 / 1% component A-107 / 6% component C-4 / 0.2% component B-2) was filled into the wound site. Since this solution has good fluidity, the wound can be sufficiently filled and permeated with the hydrogel precursor solution. Then, by irradiating with a 395 nm LED light source, a hydrogel was formed in situ at the oral defect site, thereby realizing closure of the oral wound surface. Furthermore, as a result of comparing the repair effect of the oral wound of SD rats within 7 days by the in situ formed hydrogel, the preformed hydrogel, and the washing treatment with only physiological saline, the speed of wound repair by the in situ formed hydrogel was obviously faster than the other two groups, the contraction area of ​​the wound on the 7th day was the largest, and a good repair effect was achieved. In contrast, the preformed hydrogel material was difficult to fill the wound site sufficiently. In addition, there is no covalently bonded gap-free interface between tissues, so it does not have good tissue integration. It is difficult for new cells and tissues to quickly enter the hydrogel material and fully play the role of a scaffolding material. Therefore, the repair speed and effect of pre-formed hydrogels are worse than those of in situ formed hydrogels. The wounds not filled with hydrogels have the slowest repair speed, indicating that the photocrosslinkable hydrogel has a promoting effect on the repair of oral ulcers as a cell scaffolding material.

[0278] Other hydrogel systems with different material compositions (Component A: Component A-1 to Component A-154, Component B: Component B-1 to Component B-3, Component C-1 to Component C-21) belong to photocrosslinkable hydrogels and can be similarly applied to wound closure-oral ulcers.

[0279] Example 174: Sealing tissue leaks - Use of photocrosslinkable hydrogels in sealing intestinal leaks New Zealand male white rabbits were used to perform a cecal leakage sealing experiment, divided into two groups (a: hydrogel-treated (2% component A-1 / 1% component A-107 / 6% component C-4 / 0.2% component B-2) group, b: untreated control group). In the experiment, a leakage model was created in the rabbit's cecum, and then a hydrogel precursor solution was applied to the wound, allowed to fully penetrate, and then gelled in situ by light irradiation. In this way, the gelled hydrogel can firmly adhere to the defect site without the need for separate fixation. Four weeks after surgery, the experimental rabbits were euthanized by intravenous injection of air, and the cecum was removed to evaluate the repair effect. As a result, no leakage occurred in the cecum closed with hydrogel, while severe leakage occurred in the cecum not treated with hydrogel. After several weeks of repair, the defect site of the cecum treated with hydrogel was significantly repaired, indicating that the hydrogel is advantageous in effectively closing leakage and repairing postoperative damaged tissue.

[0280] Other hydrogel systems with different material compositions (Component A: Component A-1 to Component A-154, Component B: Component B-1 to Component B-3, Component C-1 to Component C-21) belong to photocrosslinkable hydrogels and can be similarly applied to tissue leakage sealing / intestinal wall leakage sealing.

[0281] Example 175: Use of photocrosslinkable hydrogels in tissue leakage sealing - surgical sutures New Zealand male white rabbits were used and divided into three groups (a: hydrogel-treated (2% component A-1 / 1% component A-107 / 6% component C-4 / 0.2% component B-2) group, b: surgical suture-treated group, c: untreated control group) for the surgical suture experiment. In the experiment, a wound suture model was created on the rabbit's abdomen. In group a, the wound was closed by applying a hydrogel precursor solution to the wound, allowing it to penetrate sufficiently, and then gelling in situ by light irradiation. The effect of tissue suture is achieved by the excellent tissue adhesive power of the hydrogel. In group b, the wound was treated with a normal surgical suture. In group c, the wound was not treated. Two weeks after the surgery, the experimental rabbits were euthanized by intravenous injection of air, and the repair effect was evaluated. As a result, the wounds treated with the hydrogel showed almost the same good suture effect as the surgical suture group, while the untreated wounds could not be effectively joined. After 4 weeks of repair, the tissues at the defect site treated with the hydrogel were attached and showed a significant repair effect, thus indicating that the hydrogel can effectively suture the wound and is advantageous for repairing postoperative damaged tissue.

[0282] Other hydrogel systems with different material compositions (Component A: Component A-1 to Component A-154, Component B: Component B-1 to Component B-3, Component C: Component C-1 to Component C-21) belong to photocrosslinkable hydrogels and can be similarly applied to tissue leakage sealing-surgical sutures.

[0283] Example 176: Hemostatic material - Use of photocrosslinkable hydrogel in liver hemostasis The hemostatic effect of hydrogel was evaluated using SD rats. Three groups (a: gelatin sponge group, b: hydrogel-treated (2% component A-1 / 1% component A-107 / 6% component C-4 / 0.2% component B-2) group, c: positive control group) were used to conduct a liver hemostatic experiment. The experimental rats were anesthetized by intraperitoneal injection of chloral hydrate (4% aqueous solution) (injection amount: 0.9 ml / 100 g), and then the hair on the anterior chest area of ​​the rats was completely shaved using a shaver and disinfected with iodine tincture. Next, an incision of about 4 cm was made along the midline of the thoracic cavity, and the thoracic cavity was opened to expose the liver area. An incision of about 2 cm was made in the left lobe of the liver. In group a, hemostasis was performed with gelatin sponge. In group b, a hydrogel precursor solution was added to the incision to cover the cut surface, and the incision was gelled and hemostasis was performed by irradiating with a 395 nm LED for 2 minutes. In group c, the liver was not treated, and the blood oozing out from the incision was allowed to naturally clot. After removing the oozing blood with gauze, the amount of bleeding and the bleeding time were recorded by the weight loss method (Figure 7). After the experiment, in group a, the gelatin sponge on the incision surface was left inside the rat's body and sutured. In group b, the hydrogel crosslinked in situ at the incision surface to separate the wound, and the liver was returned to the thoracic cavity and sutured. In group c, the liver was sutured as it was without treatment. After 14 days, the recovery status of the SD rat liver was observed. The rats were euthanized by intraperitoneally injecting an excessive amount of anesthetic chloral hydrate (4% aqueous solution, 2.7 ml / 100 g), the thoracic cavity was opened along the midline of the thoracic cavity, and the recovery status of the rat liver in the three groups was observed and recorded by taking photographs. In addition, tissue was sampled from the site of liver injury, fixed in 4% formalin solution for 2 days, dehydrated, embedded in paraffin, and tissue sections (thickness: 5 μm) were made using a slicer. Finally, the samples were stained with H&E and photographed under an optical microscope for observation and recording. The experimental results showed that in group b, the liver recovery was good, the hydrogel was completely decomposed, no adhesion occurred, and new liver tissue was formed at the incision of the liver. In group a, the gelatin sponge in the rat's body did not decompose, and the adhesion between the rat's organs and the retina was severe. In group c, adhesion between the liver and the retina was widespread. In the experimental group, after H&E staining, the liver surface was smooth and moist, the blood vessels were abundant, and the liver interface was clearly visible, while the liver with adhesion had an uneven liver interface after H&E staining, adhesion between the liver and retina tissue, and accumulation of inflammatory cells at the interface.

[0284] Other hydrogel systems with different material compositions (component A: component A-1 to component A-154, component B: component B-1 to component B-3, component C-1 to C-21) belong to photocrosslinkable hydrogels and can be similarly applied to hemostatic materials - liver hemostasis.

[0285] Example 177: Hemostatic material - Use of photocrosslinkable hydrogel in bone cross-section hemostasis New Zealand male white rabbits were used to conduct a bone cross-section hemostasis experiment, divided into three groups (a: hydrogel-treated (2% component A-1 / 1% component A-107 / 6% component C-4 / 0.2% component B-2) group, b: bone wax-treated group, c: untreated control group). In the experiment, a bone cross-section bleeding model was constructed in the rabbit femur. In group a, a hydrogel precursor solution was applied to the wound, and after sufficient penetration, it was gelled in situ by light irradiation, thereby achieving effective closure of the bone cross-section bleeding. The excellent tissue adhesive strength and photocuring speed of the hydrogel provided a timely and effective hemostasis effect. In group b, the bleeding wound was treated with normal bone wax. In group c, the bleeding wound was not treated. Eight weeks after the operation, the experimental rabbits were euthanized by intravenous injection of air and samples were taken to evaluate the repair effect. As a result, the wounds treated with hydrogel were effectively hemostasised, almost the same as the effect of the bone wax group, while the untreated wounds had persistent bleeding. After 2 weeks of repair, the original wound bleeding site showed a significant tissue recovery with hydrogel treatment, while the wound treated with bone wax did not recover, mainly because bone wax does not decompose in the body. However, the hydrogel can effectively achieve hemostasis of the bone cross section and is favorable for the repair of damaged tissue after surgery.

[0286] Other hydrogel systems with different material compositions (component A: component A-1 to component A-154, component B: component B-1 to component B-3, component C-1 to C-21) belong to photocrosslinkable hydrogels and can be similarly applied to hemostatic materials-bone cross-section hemostasis.

[0287] Example 178: Hemostatic materials - Use of photocrosslinkable hydrogels in arterial hemostasis New Zealand male white rabbits were used to conduct an arterial hemostasis experiment, divided into three groups (a: hydrogel-treated (2% component A-1 / 1% component A-107 / 6% component C-4 / 0.2% component B-2) group, b: hemostatic forceps-treated group; c: untreated control group). In the experiment, a bleeding model was constructed in the rabbit's femoral artery. In group a, the hydrogel precursor solution was applied to the wound, allowed to penetrate sufficiently, and then gelled in situ by light irradiation, achieving effective closure of femoral artery bleeding. The excellent tissue adhesive strength and light-effect speed of the hydrogel provided a timely and effective hemostatic effect. In group b, the bleeding wound was treated with a normal hemostatic forceps. In group c, the bleeding wound was not treated. Two weeks after the operation, the experimental rabbits were euthanized by intravenous injection of air, and samples were taken to evaluate the repair effect. As a result, the wounds treated with hydrogel were effectively hemostatically controlled, almost the same as that of hemostat, while the untreated wounds continued to bleed. After 2 weeks of repair, the original wound bleeding site was significantly restored by hydrogel treatment, suggesting that hydrogel can effectively achieve hemostasis in the femoral artery and is favorable for the repair of damaged tissue after surgery.

[0288] Other hydrogel systems with different material compositions (component A: component A-1 to component A-154, component B: component B-1 to component B-3, component C-1 to C-21) belong to photocrosslinkable hydrogels and can be similarly applied to hemostatic materials - arterial hemostasis.

[0289] Example 179: Hemostatic materials - Use of photocrosslinkable hydrogels in cardiac hemostasis New Zealand male white rabbits were used to conduct cardiac hemostasis experiments, divided into three groups (a: hydrogel-treated (2% component A-1 / 1% component A-107 / 6% component C-4 / 0.2% component B-2) group, b: gelatin sponge-treated group, and c: untreated control group). In the experiment, a bleeding model was constructed in the rabbit heart. In group a, a hydrogel precursor solution was applied to the wound, allowed to fully penetrate, and then gelled in situ by light irradiation, achieving effective closure against cardiac hemorrhage. The excellent tissue adhesive strength and light-effect speed of the hydrogel provided a timely and effective hemostasis effect. In group b, the bleeding wound was treated with a normal gelatin sponge. In group c, the bleeding wound was not treated. Two weeks after the operation, the experimental rabbits were euthanized by intravenous injection of air and samples were taken to evaluate the repair effect. As a result, the wounds treated with the hydrogel were effectively hemostasised, which was better than the hemostasis effect of the gelatin sponge, while the untreated wounds had persistent bleeding. After two weeks of repair, the original wound bleeding site had a significant tissue recovery due to hydrogel treatment, and the repair effect was better than that of gelatin sponge. Therefore, the hydrogel can effectively achieve cardiac hemostasis and is advantageous for the repair of damaged tissue after surgery.

[0290] Other hydrogel systems with different material compositions (component A: component A-1 to component A-154, component B: component B-1 to component B-3, component C-1 to C-21) belong to photocrosslinkable hydrogels and can be similarly applied to hemostatic materials - cardiac hemostasis.

[0291] Example 180: Tissue engineering scaffolds - Use of photocrosslinkable hydrogels in cartilage repair New Zealand male white rabbits were used and divided into three groups (a: hydrogel containing chondrocytes (2% component A-1 / 1% component A-107 / 6% component C-4 / 0.2% component B-2), i.e., Gel + chondrocyte group; b: simple hydrogel (2% component A-1 / 1% component A-107 / 6% component C-4 / 0.2% component B-2), i.e., Gel group; c: untreated control group, i.e., Control group) to conduct an articular cartilage repair experiment. In the experiment, the hydrogel precursor solution was sufficiently permeated and filled into the defect site of the rabbit's articular cartilage, and after gelation by light irradiation, it could be firmly attached to the defect site without the need for separate fixation. 12 weeks after the operation, the experimental rabbits were euthanized by intravenous injection of air, and the damaged joint was removed to evaluate the repair effect. As can be seen from the photographic results of the damaged area of ​​rabbit articular cartilage, after 12 weeks, in the Gel+ chondrocyte group, smooth new cartilage tissue was formed at the joint defect site and was well integrated with the old cartilage tissue. In the Gel group, the cartilage was also repaired to a certain extent, but the outline of the cartilage wound caused by surgery was still visible. In the Control group, the cartilage tissue was almost not repaired, and obvious holes remained at the damaged area. Next, the repair status of the cartilage in each group was evaluated by H&E staining. As a result of H&E staining, both the Gel+ chondrocyte group and the Gel group formed new tissue and well integrated with the old cartilage tissue, but the new tissue in the Gel+ chondrocyte group was thicker than the Gel group and had a flat surface, and it was difficult to find obvious new tissue in the Control group. Furthermore, the components of the new cartilage were analyzed by Safranin O and immunohistochemical staining. The new cartilage tissues of the Gel+ chondrocyte group and the Gel group both showed Safranin O staining activity, indicating that the glycoprotein components of normal cartilage were contained in the new cartilage tissue. In addition, the newly formed cartilage tissues of both the Gel+chondrocyte group and the Gel group showed type II collagen staining activity, indicating that the cartilage tissue contained a large amount of type II collagen. The results of Safranin O and immunohistochemical staining demonstrated that the newly formed cartilage tissue was transparent cartilage by repairing cartilage with the new photocrosslinkable hydrogel material.

[0292] Other hydrogel systems with different material compositions (component A: component A-1 to component A-154, component B: component B-1 to component B-3, component C-1 to component C-21) belong to photocrosslinkable hydrogels and can be similarly applied to tissue engineering scaffold materials for cartilage repair.

[0293] Example 181: Tissue engineering scaffolds - Use of photocrosslinkable hydrogels in bone repair Skull repair experiments were conducted using SD rats, randomly divided into three groups (a: hydrogel (2% component A-1 / 1% component A-107 / 6% component C-4 / 0.2% component B-2) + hydroxyapatite experimental group, b: hydrogel treatment (2% component A-1 / 1% component A-107 / 6% component C-4 / 0.2% component B-2) group, c: untreated control group). In the experiment, the rats were anesthetized intraperitoneally with 4% chloral hydrate solution (0.9 mL / g (body weight)) and disinfected with iodine tincture. Then, the scalp of the rat skull was opened using a surgical scalpel. A complete skull defect model with a diameter of 5 mm was constructed symmetrically on the rat skull using a tooth ring drill. In the experimental group, 200 μL of hydrogel precursor solution was filled into the skull defect site of the SD rat, permeated to the wound edge, and illuminated with a 395 nm LED light source (20 mW / cm 2 ) for 30 seconds to completely gel the gel, and finally the rat scalp was sutured with a suture line. In the control group, after constructing the SD rat skull defect model, the scalp was sutured without any treatment. The SD rats were kept in a sterile environment at 37°C for 8 weeks. After that, the repair status of the SD rat skull in each group was evaluated by micro-CT scanning imaging. As a result, in the untreated control group, the skull defect of the SD rats was almost not repaired, and new stomachAlthough bone was formed, the amount of new bone tissue was small, and most of the defect sites were not well repaired, whereas the skull defect sites filled with hydrogel + hydroxyapatite were almost repaired, and a large amount of new bone tissue was formed in the defect sites. Histological staining analysis was then performed on the skull tissue sections by Van Gieson staining method. As a result, complete new bone tissue was formed in the skull defect sites of SD rats treated with hydrogel + hydroxyapatite, while only a small amount of new bone tissue was formed in the skull defect sites treated with hydrogel only, and the bone tissue in most of the defect sites was still in a defective state. In the control group, almost no new bone tissue was formed. This histological staining result further demonstrated that the hydrogel wrapped with hydroxyapatite has a good repair effect on bone defects.

[0294] Other hydrogel systems with different material compositions (component A: component A-1 to component A-154, component B: component B-1 to component B-3, component C-1 to component C-21) belong to photocrosslinkable hydrogels and can be similarly applied to tissue engineering scaffold materials for bone repair.

[0295] Example 182: Tissue engineering scaffold material - Use of photocrosslinkable hydrogel in bone / cartilage complex defect repair A pig was used as an animal model. The cartilage material was hydrogel + chondrocytes, and the bone material was hydrogel + hydroxyapatite + BMSCs. The animals were divided into two groups (a: hydrogel (2% component A-1 / 1% component A-107 / 6% component C-4 / 0.2% component B-2) containing chondrocytes and BMSCs, i.e., Gel + cell group; b: simple hydrogel (2% component A-1 / 1% component A-107 / 6% component C-4 / 0.2% component B-2), i.e., Gel group) to conduct an experiment on repairing a composite defect in an articular bone / cartilage. In the experiment, the bone material was first filled into the bone defect site, and the gel precursor solution was sufficiently permeated and gelled by light irradiation, so that the hydrogel firmly adhered to the bone defect site. Next, the cartilage material was filled into the cartilage defect site, and the gelled by light irradiation, so that the hydrogel firmly adhered to the cartilage defect site (Figure 8). Six months after the operation, the experimental pigs were euthanized, and the damaged joints were removed to evaluate the repair effect. In the Gel+ cell group, smooth new cartilage and bone tissues were formed at the joint defect site, and the old cartilage / bone tissues were well integrated, and the cartilage and bone tissues were also well integrated. In the Gel group, the bone / cartilage tissues were hardly repaired, and obvious holes still remained at the damaged site. Next, the repair status of the cartilage in each group was evaluated by H&E staining. As a result of H&E staining, in the Gel+ cell group, new tissues were formed and well integrated with the old cartilage tissues, while in the Gel group, obvious new tissues were difficult to find. Furthermore, the components of the new cartilage were analyzed by Safranin O and immunohistochemical staining. In the Gel+ cell group, the new cartilage tissue showed Safranin O staining activity, indicating that the glycoprotein components of normal cartilage were contained in the new cartilage tissue. In addition, the new cartilage tissue of the Gel+ cell group showed type II collagen staining activity, indicating that the cartilage tissue contained a large amount of type II collagen. The results of the Safranin O and immunohistochemical staining demonstrated that the newly formed cartilage tissue was transparent cartilage by repairing the cartilage with the new photocrosslinkable hydrogel material. Then, histological staining analysis was performed on the bone tissue sections by Van Gieson staining method. As a result, in the Gel+ cell group, only a small amount of new bone tissue was formed in the bone defect site, and the bone tissue in most defect sites was still in a defective state.The histological staining results further demonstrated that the cell-laden hydrogel had a good repair effect on bone defects.

[0296] Other hydrogel systems with different material compositions (component A: component A-1 to component A-154, component B: component B-1 to component B-3, component C-1 to component C-21) belong to photocrosslinkable hydrogels and can be similarly applied to tissue engineering scaffold materials-bone / cartilage composite defect repair.

[0297] Example 183: Use of photocrosslinkable hydrogels in bioinks for 3D printing (FDM) 3D printing technology is a three-dimensional molding technology that has developed rapidly in recent years and has already been widely used. At present, 3D printing technologies include fused deposition modeling (FDM), selective laser sintering (SLA), selective laser sintering (SLS), continuous liquid level manufacturing (CLIP), etc. However, the method suitable for cell printing is mainly the FDM method. Since the material for cell printing is mainly hydrogel material, the development of bioink-printable hydrogel material for 3D printing and the improvement of the printing resolution of hydrogel material have become fundamental problems in the field. Using component A-1 (i.e., HA-NB) prepared in Example 1, component A-107 (i.e., HAMA), component C-4 (i.e., gelatin), component B-2 (i.e., LAP) prepared in Example 155, component A-88 (i.e., HA-cNB) prepared in Example 88, component A-144 (i.e., HA-cNB-MA) prepared in Example 144, and component B-2 (i.e., LAP) prepared in Example 155 as examples, a hydrogel precursor solution of a certain mass concentration was mixed uniformly with cells, and then placed in a low-temperature print barrel, the print temperature was controlled to about 25°C, and the viscosity of the bioink was adjusted by adjusting the temperature to obtain an optimal print condition. Then, appropriate print pressure and print speed were determined to perform bioprinting of different structures, and after printing, the hydrogel was crosslinked by light irradiation (or light was irradiated while printing) to obtain a hydrogel containing cells and having a structure, and then 3D cell culture was performed (Figure 9).

[0298] Other hydrogel systems with different material compositions (component A: component A-1 to component A-154, component B: component B-1 to component B-3, component C-1 to component C-21) belong to photocrosslinkable hydrogels and can be similarly applied to bioinks for 3D printing (FDM).

[0299] Example 184: Use of photocrosslinkable hydrogels in bioinks for 3D printing (DLP) DLP (Digital Light Processing) 3D printing technology is a new photocuring printing method that has been developed in recent years. Compared with SLA (three-dimensional photocuring molding) type printers, DLP has advantages that most printing methods cannot compare with due to its fast printing speed and high resolution. At present, there is a certain degree of prospect in the fields of dental models, jewelry design, etc. The only printing inks available on the market are photocuring resins, and hydrogels have not yet attracted attention as new bioinks, especially because there are no hydrogel materials suitable for DLP printing. The composite photocrosslinkable hydrogel material of the present invention is very suitable for 3D printing due to its fast photocuring speed and excellent mechanical properties, and has higher printing accuracy. Using component A-1 (i.e., HA-NB) prepared in Example 1, component A-107 (i.e., HAMA) prepared in Example 107, component C-4 (i.e., gelatin), component B-2 (i.e., LAP) prepared in Example 155, component A-88 (i.e., HA-cNB) prepared in Example 88, component A-144 (i.e., HA-cNB-MA) prepared in Example 144, and component B-2 (i.e., LAP) prepared in Example 155 as examples, a hydrogel precursor solution with a certain mass concentration was uniformly mixed with cells and then placed in a liquid tank, and the printing conditions of the bioink were adjusted by adjusting parameters such as the intensity of the light source and the exposure time to obtain the optimal printing conditions. do. This allows for the creation of structured hydrogels that are both cellular and structurally relevant, allowing the study of 3D cell cultures.

[0300] Other hydrogel systems with different material compositions (component A: component A-1 to component A-154, component B: component B-1 to component B-3, component C-1 to component C-21) belong to photocrosslinkable hydrogels and can be similarly applied to bioinks for 3D printing (DLP).

[0301] Example 185: Use of photocrosslinkable hydrogels in drug coating and release Hydrogels are cross-linked polymer networks that can swell in water but do not dissolve. Hydrogels are mostly composed of water, so they have very good biocompatibility and are particularly used as carriers for drugs and large bioactive molecules. Drugs or large bioactive molecules encapsulated in hydrogel materials achieve sustained drug release through the diffusion and decomposition of the molecules and the material. The following takes the coating and release of drugs as an example. Component A-1 (i.e., HA-NB) prepared in Example 1, component A-107 (i.e., HAMA), component C-4 (i.e., gelatin), component B-2 (i.e., LAP) prepared in Example 155, component A-88 (i.e., HA-cNB) prepared in Example 88, component A-144 (i.e., HA-cNB-MA) prepared in Example 144, and component B-2 (i.e., LAP) prepared in Example 155 were dissolved in saline to prepare a hydrogel precursor solution of a certain mass concentration, and a certain amount of drug molecules was added, and 200 μL of the solution was placed in a circular mold and irradiated with light to form a hydrogel, which was then placed in a 24-well cell culture plate and a certain amount of saline was added to carry out a drug release experiment. The amount of drug released in the solution was analyzed by UV irradiation test, and the effect of this material on drug release was evaluated based on the results.

[0302] Other hydrogel systems with different material compositions (component A: component A-1 to component A-154, component B: component B-1 to component B-3, component C-1 to component C-21) belong to photocrosslinkable hydrogels and can be similarly applied to drug coating and release.

[0303] The above description of the embodiments is provided for those skilled in the art to understand and use the present invention. Those skilled in the art can make various modifications to these embodiments and can apply the general principles described herein to other embodiments without creative effort. Therefore, the present invention is not limited to the above embodiments, and any improvements and modifications made by those skilled in the art according to the teachings of the present invention without departing from the spirit of the present invention are included in the scope of protection of the present invention.

Claims

1. 1. A method for producing a photocrosslinkable hydrogel material, comprising the steps of: Component A - dissolving a photopolymer derivative in a biocompatible medium to obtain a photopolymer solution A; Component B - dissolving a photoinitiator in a biocompatible medium to obtain a photoinitiator solution B; uniformly mixing solution A and solution B to obtain a hydrogel precursor solution; and irradiating the hydrogel precursor solution with a light source, so that the o-nitrobenzyl-based phototrigger and / or double bond functional group in component A and the component B-photoinitiator undergo radical crosslinking under light irradiation to form a hydrogel; The component A-photosensitive polymer derivative is one or more selected from the following substances: 1) A photosensitive polymer derivative modified with an o-nitrobenzyl-based phototrigger having the structure of formula AI; 2) A photosensitive polymer derivative containing both an o-nitrobenzyl-based phototrigger and a double bond functional group, having the structure of formula A-III: [Formula 1] Wherein, the o-nitrobenzyl-based phototrigger has the structure of structural formula I-1, as shown in formula I: [Case 2] In formula I-1, when X=O, it is an o-nitrobenzyl-based phototrigger, when X=S, it is an o-nitrobenzylthio-based phototrigger, and when X=NH, it is an o-nitrobenzylamino-based phototrigger; In formulae AI, A-III, I and I-1, R' is selected from the group consisting of hydrogen, halogen, a hydroxyl group, a mercapto group, an amino group, a nitro group, a cyano group, an aldehyde group, a keto 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 and a modified alkyl group; In formula I-1, R １is selected from the group consisting of hydrogen, ether-linked substituents, ester-linked substituents, carbonate-linked substituents, urethane-linked substituents, mercaptocarboxylic ester-linked substituents, or phosphate ester-linked substituents; In formula I-1, R ２ , R ３ , R ４ , R ５ is selected from the group consisting of hydrogen, halogen, a hydroxyl group, a mercapto group, an amino group, a nitro group, a cyano group, an aldehyde group, a keto 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, and a modified alkyl group; In formula A-III, R' １ , R' ２ , R' ３ is selected from the group consisting of hydrogen, an alkyl group, a modified alkyl group, or an aryl group; R' ４ is selected from the group consisting of ether-linked substituents, ester-linked substituents, and amide-linked substituents; In Formula AI and Formula A-III, n is 2 or more, and P １ is a hydrophilic or water-soluble natural or synthetic polymer, or P １ are independently selected from the group consisting of a variety of hydrophilic or water-soluble natural or synthetic polymers; Component B - photoinitiator is a substance capable of generating radicals under irradiation with light; A method for producing a photocrosslinkable hydrogel material.

2. In formula A-III, R' １ , R' ２ , R' ３ The method for producing a photocrosslinkable hydrogel material according to claim 1, characterized in that:

3. In the structure represented by formula I-1, R ２ , R ３ , R ４ , R ５are bonded to each other and together with the carbon atom form a saturated or unsaturated aliphatic ring or heterocycle, or form an aromatic ring or aromatic heterocycle.

4. 2. The method for producing a photocrosslinkable hydrogel material according to claim 1, characterized in that component B--photoinitiator is a water-soluble photoinitiator or a water-dispersible photoinitiator.

5. The method for producing a photocrosslinkable hydrogel material according to claim 1, characterized in that the component B-photoinitiator is component B-1, component B-2 or component B-3, or a derivative of component B-1, component B-2 or component B-3. [C3]

6. Component A further includes a double bond functional group-containing photosensitive polymer derivative, the double bond functional group-containing photosensitive polymer derivative having a structure of formula A-II, [C4] In formula A-II, R' １ , R' ２ , R' ３ is selected from the group consisting of hydrogen, an alkyl group, a modified alkyl group, or an aryl group; R' ４ is selected from the group consisting of ether-linked substituents, ester-linked substituents, and amide-linked substituents; In formula A-II, n is 2 or more, and P １ The method for producing a photocrosslinkable hydrogel material according to claim 1, characterized in that is a hydrophilic or water-soluble natural polymer or a hydrophilic or water-soluble synthetic polymer.

7. In formula A-II, R' １ , R' ２ , R' ３ The method for producing a photocrosslinkable hydrogel material according to claim 6, characterized in that:

8. The alkyl group is a saturated or unsaturated aliphatic linear or branched alkyl group having 1-30 carbon atoms; The modified alkyl group is such that any carbon atom of the alkyl group is not substituted with a halogen atom, —OH, —SH, or —NO ２ , -CN, -CHO, -COOH, an ester group, an amide group, an aryl group, an arylene group, -CO-, -O-, -S-, -SO-, -SO ２ -, a primary amino group, a secondary amino group, a tertiary amino group, a quaternary ammonium base, a saturated or unsaturated monocyclic or bicyclic cycloalkylene group, and a bridged aliphatic heterocycle, said modified alkyl group having 1-30 atoms, the carbon-carbon single bond of which may be optionally replaced by a carbon-carbon double bond or a carbon-carbon triple bond; The phosphate ester linked substituents are -POOO(CH ２ ) ｘ CH ３ , -POOO(CH ２ CH ２ O) ｘ CH ３ , -POOO(CH ２ ) ｘ (CH ２ CH ２ O) ｙ CH ３ where x and y are integers equal to or greater than 0; the aryl group is a 5-10 membered aromatic monocyclic or aromatic fused bicyclic structure; The heteroaryl group is a 5-10 membered aromatic monocyclic or fused bicyclic ring structure containing at least one heteroatom selected from the group consisting of O, S, N or Si on the ring; the halogen atoms are each independently selected from the group consisting of F, Cl, Br, and I; the aliphatic ring is a saturated or unsaturated 3- to 10-membered monocyclic or polycyclic aliphatic ring, The aliphatic heterocycle is a saturated or unsaturated 3- to 10-membered monocyclic or polycyclic aliphatic heterocycle containing at least one heteroatom selected from the group consisting of O, S, N, or Si on the ring, When the aliphatic heterocycle contains an S atom, it is -S-, -SO- or -SO ２ -, wherein H in the aliphatic ring or heterocycle may be optionally substituted with a halogen atom, a nitro group, an aryl group, an alkyl group or a modified alkyl group; the aromatic ring is a 5- to 10-membered aromatic monocyclic ring or an aromatic condensed bicyclic ring; The method for producing a photocrosslinkable hydrogel material according to claim 3, characterized in that the aromatic heterocycle is a 5-10 membered aromatic monocycle or aromatic condensed bicycle containing at least one heteroatom selected from the group consisting of O, S, N, or Si on the ring, and H in the aromatic ring or aromatic heterocycle may be optionally substituted with a halogen atom, a nitro group, an aryl group, an alkyl group, or a modified alkyl group.

9. When component A is a photosensitive polymer derivative modified with an o-nitrobenzyl-based phototrigger having the structure of formula AI, One end of P1 is R ２ , R ３ , R ４ , R ５ any one or more groups among ２ , R ３ , R ４ , R ５ a saturated or unsaturated aliphatic or heterocyclic ring formed by ２ , R ３ , R ４ , R ５ and is bonded to an aromatic ring or aromatic heterocycle formed by The linking bond is a linking bond P obtained from a hydroxyl system. １ -O-, a linking bond P obtained from a mercapto system １ -S-, an amino-based linking bond P １ -NH-, an alkane-based linking bond P １ -, a linking bond P obtained by an ester bond system, selected from the group consisting of １ -COO- or an amide bond system is obtained by connecting the bond P １-CONH-, and one end of the connecting bond is P １ and the other end is bonded to a benzene ring of a molecule represented by formula AI.

10. When component A is a photosensitive polymer derivative containing both an o-nitrobenzyl-based phototrigger having the structure of formula A-III and a double bond functional group, P １ One end of R ２ , R ３ , R ４ , R ５ any one or more groups among ２ , R ３ , R ４ , R ５ a saturated or unsaturated aliphatic or heterocyclic ring formed by ２ , R ３ , R ４ , R ５ and is bonded to an aromatic ring or aromatic heterocycle formed by P １ The other end of R' ４ is bound to The linking bond is a hydroxyl-based linking bond -O-P １ -O-, and the linking bond -S-P obtained from the mercapto system １ -S-, and the resulting amino-based linkage -NH-P １ -NH-, an alkane-based linking bond -P １ -, a linking bond obtained by an ester bond system -COO-P １ -COO- or a linking bond obtained by an amide bond system -CONH-P １ or the linking bond is selected from the group consisting of P １ and one end of the linking bond is selected from the group consisting of a linking bond having two or more of the hydroxyl, mercapto, amino, alkane, ester bond, and amide bond attached to both ends thereof, １and the other end is bonded to a benzene ring of the molecule represented by formula A-III.

11. The hydrophilic or water-soluble natural polymer is selected from natural polysaccharide substances, modified or degraded products thereof, proteins, modified, modified and degraded products thereof, The natural polysaccharide material is selected from hyaluronic acid, carboxymethylcellulose, methylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, alginic acid, glucan, agarose, heparin, chondroitin sulfate, ethylene glycol chitosan, propylene glycol chitosan, chitosan lactate, carboxymethyl chitosan, or chitosan quaternary ammonium salt; The protein includes various hydrophilic or water-soluble animal and plant proteins, collagen, serum protein, silk fibroin, and elastin, and the decomposition product of the protein is selected from gelatin or polypeptide; The method for producing a photocrosslinkable hydrogel material according to claim 1 or 6, characterized in that the hydrophilic or water-soluble synthetic polymer is selected from two-arm or multi-arm polyethylene glycol, polyethyleneimine, dendrimers, synthetic polypeptides, polylysine, polyglutamic acid, polyacrylic acid, polymethacrylic acid, polyacrylate, polymethacrylate, polyacrylamide, polymethacrylamide, polyvinyl alcohol, and polyvinylpyrrolidone.

12. The polymer derivative modified with an o-nitrobenzyl-based phototrigger of the formula AI is selected from the group consisting of the following structures of component A: [Case 5a] [C5b] [Case 5c] [C5d] [5e] The polymer derivative modified with an o-nitrobenzylthio-based optical trigger of the formula AI is selected from the group consisting of the following structures of component A: [chemical 6a] [C6b] The polymer derivative modified with an o-nitrobenzylamino-based optical trigger of the formula AI is selected from the group consisting of the following structures of component A: [C7a] [C7b] The method for producing a photocrosslinkable hydrogel material according to claim 1, characterized in that in components A-1 to A-87, n is 2 or more, and in the copolymers of components A-50, A-69 and A-87, x and y represent the degree of polymerization of each component of the copolymer, HA is hyaluronic acid, CMC is carboxymethylcellulose, Alg is alginic acid, CS is chondroitin sulfate, PGA is polyglutamic acid, PEG is polyethylene glycol, Chitosan is chitosan, Gelatin is gelatin, PLL is polylysine, Dex is glucan, and Hep is heparin.

13. The double bond-modified polymer derivative of the formula A-II is selected from the group consisting of the following structures of component A-107 to component A-115: [C8] The method for producing a photocrosslinkable hydrogel material according to claim 6, wherein in Components A-107 to A-115, n is 2 or more.

14. The polymer derivative containing both the o-nitrobenzyl-based phototrigger and the double bond functional group is selected from the group consisting of the following structures of Component A-116 to Component A-143: [Case 9a] [C9b] The method for producing a photocrosslinkable hydrogel material according to claim 1, characterized in that in components A-116 to A-143, n is 2 or more, HA is hyaluronic acid, CMC is carboxymethylcellulose, PEG is polyethylene glycol, Chitosan is chitosan, and Gelatin is gelatin.

15. Component A - dissolving a photopolymer derivative in a biocompatible medium to obtain a photopolymer solution A; Component B - dissolving a photoinitiator in a biocompatible medium to obtain a photoinitiator solution B; A step of dissolving auxiliary component C-other biocompatible polymer derivatives in a biocompatible medium to obtain a polymer solution C, wherein the auxiliary component C-other biocompatible polymer derivatives are polymer derivatives containing amino, hydrazine, acylhydrazine or hydroxylamine functional groups, and polymer derivatives containing mercapto functional groups; 15. A method for producing a photocrosslinkable hydrogel material according to any one of claims 1 to 7 and 9 to 14, characterized in that solution A, solution B and solution C are uniformly mixed to obtain a hydrogel precursor solution, and the hydrogel precursor solution is irradiated with a light source, whereby the o-nitrobenzyl-based phototrigger and / or double bond functional group in component A and the component B-photoinitiator each undergo radical crosslinking under light irradiation, and the aldehyde group / keto group generated by the light irradiation of the o-nitrobenzyl-based phototrigger in component A undergoes photobond crosslinking with the amino, hydrazine, acylhydrazine or hydroxylamine functional group in component C, and the generated nitroso group undergoes photoinduced nitroso crosslinking with the mercapto functional group in component C to form a hydrogel.

16. The polymer derivatives containing amino, hydrazine, acylhydrazine or hydroxylamine functional groups have the structures of structural formulas C-I, C-II, C-III and C-IV, respectively, and the polymer derivatives containing mercapto functional groups have the structures of structural formulas C-V, [C10] In the structural formulae CI, C-II, C-III, C-IV, and CV, n is 2 or more, and P ２ , P ３ , P ４ , P ５ , P ６ The method for producing a photocrosslinkable hydrogel material according to claim 15, characterized in that is a hydrophilic or water-soluble natural polymer, or is a hydrophilic or water-soluble synthetic polymer.

17. The hydrophilic or water-soluble natural polymer is selected from natural polysaccharide substances, modified or degraded products thereof, proteins, modified, modified and degraded products thereof, The natural polysaccharide material is selected from hyaluronic acid, carboxymethylcellulose, methylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, alginic acid, glucan, agarose, heparin, chondroitin sulfate, ethylene glycol chitosan, propylene glycol chitosan, chitosan lactate, carboxymethyl chitosan, or chitosan quaternary ammonium salt; The protein includes various hydrophilic or water-soluble animal and plant proteins, collagen, serum protein, silk fibroin, and elastin, and the decomposition product of the protein is selected from gelatin or polypeptide; The method for producing a photocrosslinkable hydrogel material according to claim 16, characterized in that the hydrophilic or water-soluble synthetic polymer is selected from two-arm or multi-arm polyethylene glycol, polyethyleneimine, dendrimers, synthetic polypeptides, polylysine, polyglutamic acid, polyacrylic acid, polymethacrylic acid, polymethacrylate, polymethacrylate, polyacrylamide, polymethacrylamide, polyvinyl alcohol, and polyvinylpyrrolidone.

18. The formula C-I is selected from the group consisting of the structures of components C-1 to C-9 below, the formula C-II is selected from the group consisting of the structures of components C-10 below, the formula C-III is selected from the group consisting of the structures of components C-11 to C-13 below, the formula C-IV is selected from the group consisting of the structures of components C-14 to C-15 below, and the formula C-V is selected from the group consisting of the structures of components C-16 to C-21 below, [Case 11a] [C11b] The method for producing a photocrosslinkable hydrogel material according to claim 16, characterized in that, in components C-1 to C-21, n is 2 or more.

19. A photocrosslinkable hydrogel material produced by the method for producing a photocrosslinkable hydrogel material according to any one of claims 1 to 18.

20. A kit for use in the preparation of a photocrosslinkable hydrogel material according to claim 19, comprising component A - a photosensitive polymer derivative, component B - a photoinitiator, and instructions relating to the preparation and use of the hydrogel, The component A-photosensitive polymer derivative is one or more selected from the following substances: 1) A photosensitive polymer derivative modified with an o-nitrobenzyl-based phototrigger having the structure of formula AI; 2) A photosensitive polymer derivative containing both an o-nitrobenzyl-based phototrigger and a double bond functional group, having the structure of formula A-III: [C12] Wherein, the o-nitrobenzyl-based phototrigger has the structure of structural formula I-1, as shown in formula I: [C13] In formula I-1, when X=O, it is an o-nitrobenzyl-based phototrigger, when X=S, it is an o-nitrobenzylthio-based phototrigger, and when X=NH, it is an o-nitrobenzylamino-based phototrigger; In formulae AI, A-III, I and I-1, R' is selected from the group consisting of hydrogen, halogen, a hydroxyl group, a mercapto group, an amino group, a nitro group, a cyano group, an aldehyde group, a keto 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 and a modified alkyl group; In formula I-1, R １ is selected from the group consisting of hydrogen, ether-linked substituents, ester-linked substituents, carbonate-linked substituents, urethane-linked substituents, mercaptocarboxylic ester-linked substituents, or phosphate ester-linked substituents; In formula I-1, R ２ , R ３ , R ４ , R ５ is selected from the group consisting of hydrogen, halogen, a hydroxyl group, a mercapto group, an amino group, a nitro group, a cyano group, an aldehyde group, a keto 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, and a modified alkyl group; In formula A-III, R' １ , R' ２ , R' ３ is selected from the group consisting of hydrogen, an alkyl group, a modified alkyl group, or an aryl group; R' ４ is selected from the group consisting of ether-linked substituents, ester-linked substituents, and amide-linked substituents; In Formula AI and Formula A-III, n is 2 or more, and P １ is a hydrophilic or water-soluble natural or synthetic polymer, or P １ are independently selected from the group consisting of a variety of hydrophilic or water-soluble natural or synthetic polymers; Component B - a kit, characterized in that the photoinitiator is a substance capable of generating radicals under light irradiation.

21. Component A further includes a double bond functional group-containing photosensitive polymer derivative, the double bond functional group-containing photosensitive polymer derivative having a structure of formula A-II, [C14] In formula A-II, R' １ , R' ２ , R' ３ is selected from the group consisting of hydrogen, an alkyl group, a modified alkyl group, or an aryl group; R' ４ is selected from the group consisting of ether-linked substituents, ester-linked substituents, and amide-linked substituents; In formula A-II, n is 2 or more, and P １ The kit according to claim 20, characterized in that the is a hydrophilic or water-soluble natural polymer or a hydrophilic or water-soluble synthetic polymer.

22. In formula A-II, R' １ , R' ２ , R' ３ The kit of claim 21 , characterized in that:

23. A kit for use in the preparation of a photocrosslinkable hydrogel material according to claim 20 or 21, comprising component A - a photosensitive polymer derivative, component B - a photoinitiator, auxiliary component C, and instructions relating to the preparation and use of the hydrogel, said auxiliary component C is selected from polymer derivatives containing amino, hydrazine, acylhydrazine or hydroxylamine functional groups; The polymer derivatives containing an amino group, a hydrazine, an acylhydrazine or a hydroxylamine functional group have the structures of structural formulas C-I, C-II, C-III and C-IV, respectively, and the polymer derivatives containing a mercapto functional group have the structure of structural formula C-V, [C15] In the structural formulas CI, C-II, C-III, C-IV, and CV, n is 2 or more, and P ２ , P ３ , P ４ , P ５ , P ６ is a hydrophilic or water-soluble natural polymer or a hydrophilic or water-soluble synthetic polymer, The hydrophilic or water-soluble natural polymer is selected from the group consisting of natural polysaccharide substances, modified or degraded products thereof, proteins, modified, modified and degraded products thereof, The natural polysaccharide material is selected from hyaluronic acid, carboxymethylcellulose, methylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, alginic acid, glucan, agarose, heparin, chondroitin sulfate, ethylene glycol chitosan, propylene glycol chitosan, chitosan lactate, carboxymethyl chitosan, or chitosan quaternary ammonium salt; The protein includes various hydrophilic or water-soluble animal and plant proteins, collagen, serum protein, silk fibroin, and elastin, and the protein hydrolyzate is selected from gelatin or polypeptide; 1. The kit according to claim 1, wherein the hydrophilic or water-soluble synthetic polymer is selected from the group consisting of two-arm or multi-arm polyethylene glycol, polyethyleneimine, dendrimers, synthetic polypeptides, polylysine, polyglutamic acid, polyacrylic acid, polymethacrylic acid, polyacrylate, polymethacrylate, polyacrylamide, polymethacrylamide, polyvinyl alcohol, and polyvinylpyrrolidone.

24. The formula C-I is selected from the group consisting of the structures of components C-1 to C-9 below, the formula C-II is selected from the group consisting of the structures of components C-10 below, the formula C-III is selected from the group consisting of the structures of components C-11 to C-13 below, the formula C-IV is selected from the group consisting of the structures of components C-14 to C-15 below, and the formula C-V is selected from the group consisting of the structures of components C-16 to C-21 below, [Case 16a] [C16b] The kit according to claim 23, wherein n is 2 or more in components C-1 to C-21.

25. Use of said photocrosslinkable hydrogel in the manufacture of postoperative skin repair materials or drugs; Use of the photocrosslinkable hydrogel in the manufacture of a postoperative adhesion prevention material or drug; Use of said photocrosslinkable hydrogel in the manufacture of postoperative oral ulcer material or medicament; Use of the photocrosslinkable hydrogel in the manufacture of a leaky intestinal wall sealing material or drug; Use of said photocrosslinkable hydrogel in the manufacture of surgical suture materials or drugs; Use of said photocrosslinkable hydrogel in the manufacture of a liver hemostatic material or drug; Use of said photocrosslinkable hydrogel in the manufacture of bone cross-section hemostatic materials or drugs; Use of said photocrosslinkable hydrogel in the manufacture of an arterial hemostatic material or drug; Use of said photocrosslinkable hydrogel in the manufacture of a cardiac hemostatic material or drug; Use of said photocrosslinkable hydrogel in the manufacture of a cartilage repair material or drug. Use of said photocrosslinkable hydrogel in the manufacture of a bone repair material or drug. Use of said photocrosslinkable hydrogel in the manufacture of a bone / cartilage composite defect repair material or drug; Use of the photocrosslinkable hydrogel as a bioink; and 20. Use of the photocrosslinkable hydrogel material according to claim 19, characterized in that it comprises use of said photocrosslinkable hydrogel in the manufacture of cell, protein, or drug carriers.

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